Haemophilus

J Infect Dis, 1998 Dec, 178(6), 1795 - 8
Etiology of genital ulcers and prevalence of human immunodeficiency virus coinfection in 10 US cities . The Genital Ulcer Disease Surveillance Group; Mertz KJ et al.; To determine the etiology of genital ulcers and to assess the prevalence of human immunodeficiency virus (HIV) infection in ulcer patients in 10 US cities, ulcer and serum specimens were collected from approximately 50 ulcer patients at a sexually transmitted disease clinic in each city . Ulcer specimens were tested using a multiplex polymerase chain reaction assay to detect Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus (HSV); sera were tested for antibody to HIV . H . ducreyi was detected in ulcer specimens from patients in Memphis (20% of specimens) and Chicago (12%) . T . pallidum was detected in ulcer specimens from every city except Los Angeles (median, 9% of specimens; range, 0%-46%) . HSV was detected in >/=50% of specimens from all cities except Memphis (42%) . HIV seroprevalence in ulcer patients was 6% (range by city, 0%-18%) . These data suggest that chancroid is prevalent in some US cities and that persons with genital ulcers should be a focus of HIV prevention activities.

J Infect Dis, 1998 Dec, 178(6), 1688 - 97
The immune response to Haemophilus ducreyi resembles a delayed-type hypersensitivity reaction throughout experimental infection of human subjects; Palmer KL et al.; Previous work in 3 subjects infected for 2 weeks indicated that experimental infection with Haemophilus ducreyi recruits CD4 cells to the skin at the pustular stage of disease . In order to describe the kinetics of the host response, 23 subjects were infected at 2 sites with a standardized dose of H . ducreyi . Subjects were biopsied 1 or 4 days after inoculation or when they developed a painful pustular lesion (days 7-14) . Papules and pustules contained a predominant T cell infiltrate that consisted of CD45RO and CD4 cells of the alpha beta lineage . Both papules and pustules contained mixed or T helper 1 type cytokine mRNA and interleukin-8 and tumor necrosis factor-alpha mRNA . Although the subjects had no history of chancroid, their immune responses resembled delayed-type hypersensitivity reactions that occurred within 24 h of inoculation and persisted throughout the course of experimental infection.

J Infect Dis, 1998 Dec, 178(6), 1684 - 7
Standardization of the experimental model of Haemophilus ducreyi infection in human subjects; Al-Tawfiq JA et al.; Human volunteers were challenged with Haemophilus ducreyi . Twenty subjects were inoculated with 2 doses (approximately 30 cfu) of live and 1 dose of heat-killed bacteria at 3 sites on the arm . Eight subjects were assigned to biopsy 1 or 4 days after inoculation, and 12 were biopsied after they developed a painful pustular lesion or were followed until disease resolved . Papules developed at 95% of 40 sites infected with live bacteria (95% confidence interval {CI}, 83 . 1%-99.4%) . In 24 sites followed to end point, 27% of the papules resolved, 69% (95% CI, 47.1%-86.6%) evolved into pustules, and 4% remained at the papular stage . Recovery rates of H . ducreyi from surface cultures ranged from 13% to 41% . H . ducreyi was recovered from biopsies of 12 of 15 pustules and 1 of 7 papules, suggesting that H . ducreyi replicates between the papular and pustular stages of disease.

Pediatr Allergy Immunol, 1998 Aug, 9(3), 156 - 60
Protective immunogenicity of Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine in children who failed to respond to prior invasive H . influenzae type b disease; Berthet F et al.; A polyribosylribitol phosphate (polysaccharide)-tetanus protein conjugate vaccine (PRP-T) against Haemophilus influenzae type b (Hib) was evaluated for protective immunogenicity in 25 previously PRP-unimmunized children who had failed to develop protective PRP antibody levels (< 1 microg/ml) after prior invasive Hib disease at median age 10 months . Children under 21 months of age at time of PRP-T immunization received one, two or three doses . Serum was obtained for total PRP antibody, complement mediated bactericidal activity and specific IgG1 and IgG2 PRP antibodies before (n = 25), 1 to 2 months (n = 24) and > 5 months (n = 13) after completed vaccination . One to 2 months after immunization, all but one patient developed > 1 microg/ml of antibody (geometric mean level 50.7 microg/ ml) . The non-responder developed protective antibody levels when tested at 6 months after vaccination . Twenty out of 22 sera had detectable complement mediated bactericidal activity (median dilution titer 1:24), 1-2 months after vaccination . Three patients failed to demonstrate PRP antibodies in the IgG1 or IgG2 subclasses, although two of them had protective (> 1 microg/ml) total antibody levels . The second post immunization sera showed persistence of the total PRP antibody levels (geometric mean level 38.2 microg/ml) as well as of the bactericidal activity (median dilution titer 1:32) . Conclusion: PRP-T conjugate vaccine is able to elicit a protective immune response in children who have low or unmeasurable PRP antibody levels after a systemic Hib infection.

Rev Cubana Med Trop, 1995, 47(3), 189 - 94
{A growth supplement for "fastidious germs"}; Tamargo Martinez I et al.; A growth supplement for "fastidious germs" was produced at the Laboratory of Acute Respiratory Infections of "Pedro Kouri" Institute of Tropical Medicine . This supplement was studied by computerized optic spectrophotometry, and chemical composition was determined . The efficacy of this supplement for the culture of Haemophilus influenzae type b, was evidenced using 100 strains, and it was proven that it can be used in concentrations raging from 1 to 10%.

J Bacteriol, 1998 Nov, 180(22), 6013 - 22
Haemophilus ducreyi secretes a filamentous hemagglutinin-like protein; Ward CK et al.; We have identified two extremely large open reading frames (ORFs) in Haemophilus ducreyi 35000, lspA1 and lspA2, each of which encodes a predicted protein product whose N-terminal half is approximately 43% similar to the N-terminal half of Bordetella pertussis filamentous hemagglutinin (FhaB) . To the best of our knowledge, lspA1 (12,500 nucleotides {nt}) and lspA2 (14,800 nt) are among the largest prokaryotic ORFs identified to date . The predicted proteins, LspA1 and LspA2, are 86% identical overall to each other and also have limited amino acid sequence similarity at their N termini to other secreted bacterial proteins, including certain hemolysins . Southern blot analysis indicated that lspA1 and lspA2 sequences were present in 15 other geographically diverse H . ducreyi strains . Reverse transcriptase PCR analysis of total RNA isolated from H . ducreyi 35000 grown in liquid medium, grown on solid agar medium, and isolated from lesions of H . ducreyi-infected rabbits indicated that lspA1 and lspA2 were transcribed both in vitro and in vivo . A 260-kDa protein present in culture supernatant from eight virulent H . ducreyi strains reacted with both polyclonal serum from rabbits infected with H . ducreyi 35000 and a monoclonal antibody predicted to bind both LspA1 and LspA2 . This 260-kDa protein in H . ducreyi 35000 culture supernatant was shown to be the protein product of the lspA1 ORF based on its reactivity with a monoclonal antibody specific for LspA1 . Four H . ducreyi strains, previously shown to be avirulent in the temperature-dependent rabbit model for chancroid, did not produce either LspA1 or LspA2 in vitro . This finding raised the possibility that LspA1, LspA2, or both may be involved in the ability of H . ducreyi to cause lesions in this animal model.

Zentralbl Bakteriol, 1995 Oct, 282(4), 449 - 56
An immunodominant epitope on 40 kilodalton outer membrane protein is conserved among different strains of Haemophilus (Histophilus) somnus; Silva SV et al.; Four murine monoclonal antibodies (mAb) were constructed against Haemophilus (Histophilus) somnus, an important bovine pathogen, and used to analyze immunologically significant antigenic determinants on these organisms . These mAbs specifically recognized immunodominant epitopes present on the 40 kilodalton (kD) fraction of the major outer membrane protein (OMP) of H . somnus . The 9D3 IgG1 kappa mAb recognized an immunodominant epitope on the 40 kD major outer membrane protein that is conserved or shared among all the three strains (septicemic, respiratory and uro-genital) of H . somnus . Two IgM kappa mAbs (4D6 and 10C2) recognized epitope(s) on the 40 kD OMP from septicemic and respiratory strains of H . somnus but none from the whole bacterial cell preparations . Another IgM kappa mAb 9D2 recognized an antigenic determinant on the 40 kD protein from the OMP as well as a whole bacterial cell preparation of a septicemic strain of H . somnus . These data demonstrate that, at least, three immunologically significant antigenic determinants on H . somnus are defined by mAbs against this bovine pathogen . Importantly, these studies suggest that the epitope present on the 40 kD major OMP, recognized by the 9D3 mAb, is immunodominant and conserved among septicemic, respiratory and urogenital strains, and is, therefore, suitable for further investigating its use in the development of an immunodiagnostic assay and also as a recombinant vaccine.

Vet Microbiol, 1998 Aug 28, 63(1), 39 - 48
Development of a PCR test for identification of Haemophilus somnus in pure and mixed cultures; Angen O et al.; Based on the 16S rRNA sequences of a collection of well-characterized strains of Haemophilus somnus a set of primers was selected as candidates for a species-specific PCR test . All investigated H . somnus strains were found positive in the test, including 12 strains earlier found to represent H . somnus by DNA-DNA hybridization as well as representatives of the 16 ribotypes previously described within this species . The specificity of the test was evaluated on a broad collection of strains within the family Pasteurellaceae and on other Gram positive and negative species . None of these strains gave rise to an amplicon in the PCR test . The performance of the test on mixed cultures was evaluated by adding P . multocida to serial dilutions of H . somnus and incubating the agarplates for 1 and 2 days . This showed that the PCR test applied to the harvest from an agarplate can be expected to detect a single colony of H . somnus in the presence of 10(9) CFU of P . multocida even after 2 days of incubation . In conclusion, the present PCR test has been shown to represent a specific test for identification of H . somnus both in pure and mixed cultures . It represents a quick, sensitive and reliable method for identification of bacteria belonging to this phenotypically heterogeneous and often slow growing species.

Med Clin (Barc), 1998 Sep 19, 111(8), 294 - 7
{Haemophilus influenzae meningitis in adults: analysis of 12 cases}; Domingo P et al.; Haemophilus influenzae is an infrequent etiologic agent of bacterial meningitis in adult patients . In the last 12 years, it was the cause in 12 out of 238 cases (5.0%) of acute bacterial meningitis in adults . There were 5 men and 7 women with a mean age (SD) of 45.4 (16) years (range: 18-68 years) . Seven patients (60%) had a communication between subarachnoid space and skin surface or mucosal cavities, and five (41.7%) had otitis or sinusitis . Most of the strains (9/12) were serotype b . Only one patient (8.3%) developed severe neurologic and extra-neurologic complications, and was the one who died . One of the survivors (9.1%) had partial deafness . H . influenzae is not a negligible cause of bacterial meningitis in adults . Moreover, its detection has been increasing in the last years . Patients with a cerebrospinal fluid leak, otitis or sinusitis are at high risk . The outcome is usually favorable if an early adequate therapy is given.

APMIS, 1998 Sep, 106(9), 858 - 68
Intra- and interstrain differences of virulence among nontypeable Haemophilus influenzae strains; Melhus A et al.; Nontypeable Haemophilus influenzae (NTHi) is sometimes the causative agent of invasive diseases, and it has been suggested that there may be differences in virulence among NTHi strains . Whilst studying clinical isolates of NTHi in a rat model of acute otitis media, intra- and interstrain differences in virulence were observed . Two strains with suddenly reduced capacity to cause middle ear infections and one highly virulent strain with dose requirements comparable only to encapsulated H . influenzae strains were further investigated, together with 15 other H . influenzae strains . The strains were characterized by analyzing the lipopolysaccharide, the outer membrane proteins, the hemagglutinating ability, and the polymerase chain reaction products after amplification of a gene sequence associated with encapsulation . The pathogenic capacity was assessed in two different in vivo models . It was found that the two strains with reduced pathogenic capacity could regain their virulence after animal passage . The LPS analysis and the results from the chicken embryo model suggested that the observed change in virulence might be associated with the lipopolysaccharide . For the non-animal-passaged strain 3655 there were indications that an undefined factor(s) contributed to its relatively potent virulence . As all three strains lacked genes necessary for encapsulation, in no case could any part of the increased virulence be attributed to the expression of small amounts of capsule.

J Infect Dis, 1998 Oct, 178(4), 1067 - 74
Stimulation of the adherence of Haemophilus influenzae to human lung epithelial cells by antimicrobial neutrophil defensins; Gorter AD et al.; Patients with chronic obstructive pulmonary disease (COPD) frequently have recurrent lower respiratory tract infections with nonencapsulated Haemophilus influenzae . The infected mucosa of these patients is infiltrated with neutrophils, which upon activation may release antimicrobial peptides, including defensins . It was shown that defensins isolated from neutrophils or from sputum samples of COPD patients did not kill H . influenzae from these patients, but they did stimulate its adherence to human bronchial epithelial cells in a time- and dose-dependent manner . Maximal stimulation was observed after 3 h in the presence of > or = 10 micrograms/mL defensins, resulting in 65 +/- 36 cfu/cell (61-fold increase) . The enhanced adherence was not solely due to charge effects and was specifically blocked by alpha 1-proteinase inhibitor . Because adherence is the first step in the onset of respiratory tract infections, our findings indicate that neutrophil defensins likely contribute to the pathogenesis of H . influenzae infection in the lower respiratory tract.

J Infect Dis, 1998 Oct, 178(4), 1060 - 6
An investigation of genital ulcers in Jackson, Mississippi, with use of a multiplex polymerase chain reaction assay: high prevalence of chancroid and human immunodeficiency virus infection; Mertz KJ et al.; In 1994, an apparent outbreak of atypical genital ulcers was noted by clinicians at the sexually transmitted disease clinic in Jackson, Mississippi . Of 143 patients with ulcers tested with a multiplex polymerase chain reaction (PCR) assay, 56 (39%) were positive for Haemophilus ducreyi, 44 (31%) for herpes simplex virus, and 27 (19%) for Treponema pallidum; 12 (8%) were positive for > 1 organism . Of 136 patients tested for human immunodeficiency virus (HIV) by serology, 14 (10%) were HIV-seropositive, compared with none of 200 patients without ulcers (P < .001) . HIV-1 DNA was detected by PCR in ulcers of 6 (50%) of 12 HIV-positive patients . Multivariate analysis indicated that men with chancroid were significantly more likely than male patients without ulcers to report sex with a crack cocaine user, exchange of money or drugs for sex, and multiple sex partners . The strong association between genital ulcers and HIV infection in this population highlights the urgency of preventing genital ulcers in the southern United States.

Int J Pediatr Otorhinolaryngol, 1998 Sep 15, 45(1), 77 - 82
Treatment of children with secretory otitis media (SOM) with amoxicillin and clavulanic acid (Spektramox) or penicillin-V (Primcillin) . Bacteriological findings in the nasopharynx before and after treatment; Balle V et al.; A total of 386 children, aged 1-10, with secretory otitis media for at least 3 months were randomly allocated to 2 or 4 weeks' treatment with penicillin-V (Primcillin) or amoxicillin + clavulanic acid (Spektramox) . Spektramox was superior (p < 0.01) to Primcillin in eradicating Haemophilus influenzae and Branhamella catarrhalis from the nasopharynx . No difference was noted for Streptococcus pneumoniae and haemolytic streptococci, gr . A, B, C, G . No increase in the number of beta-lactamase-producing bacteria was noted after treatment . The nasopharynx was recolonized with the same bacteria within 4 weeks from cessation of treatment.

Pediatr Infect Dis J, 1998 Oct, 17(10), 913 - 8
Oral tetravalent rotavirus vaccine can be successfully coadministered with oral poliovirus vaccine and a combined diphtheria, tetanus, pertussis and Haemophilus influenzae type b vaccine . US Rhesus Rotavirus Vaccine Study Group; Markwick AJ et al.; AIM: To determine whether an oral tetravalent rotavirus vaccine (RV-TV) can be safely coadministered with a combined diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine (DTP/Hib) and oral poliovirus vaccine (OPV) to healthy infants without interfering with the immune responses to any of the component antigens . METHODS: Two hundred sixty-seven infants ages 2 to 3 months were randomly assigned in a double blind fashion to receive three doses of either placebo or RV-TV, each containing 4 x 10(5) plaque-forming units, concurrently with DTP/ Hib (Tetramune) and OPV at approximately 2, 4 and 6 months of age . Infants were followed for 5 days after each dose for the occurrence of adverse events and subsequently until 3 to 6 weeks after the third dose of RV-TV or placebo . Immune responses were assessed by measuring the postvaccination serum antibody titers to each component of DTP/ Hib and OPV at 3 to 6 weeks after the third dose . RESULTS: The percentage of infants who attained protective antibody titers and the distribution of antibody titers against diphtheria toxoid, tetanus toxoid and H . influenzae type b were not statistically different between RV-TV and placebo recipients . The distribution of antibody titers against different antigens of Bordetella pertussis (agglutinins, pertussis toxoid, filamentous hemagglutinin, fimbriae antigens and the 69-kDa outer membrane protein) was compared and no significant differences were found . The percentage of infants with detectable neutralizing antibodies against the three serotypes of poliovirus and the distribution of antibody titers was not statistically different between RV-TV and placebo recipients . There were no clinically meaningful differences in postvaccination reactions between RV-TV and placebo recipients . CONCLUSIONS: Three doses of RV-TV can be safely coadministered with three doses of DTP/ Hib and OPV without diminishing an infant's serum antibody responses to each component of these vaccines . Therefore RV-TV can be given at the standard childhood visits at 2, 4 and 6 months of age.

Pediatr Infect Dis J, 1998 Oct, 17(10), 885 - 90
Pathogens isolated during treatment failures in otitis; Gehanno P et al.; OBJECTIVES: A prospective study in the Paris region to evaluate the clinical and bacteriologic epidemiology of acute otitis media in infants in whom oral antibiotic therapy resulted in clinical failure . METHODS: The study included 186 children with a mean age of 17.5 +/- 13.1 months . Two-thirds of them attended a day-care center and 40.8% had a history of recurrent otitis media . The most frequently prescribed prior antibiotics were amoxicillin-clavulanic acid (43% of cases), an oral third generation cephalosporin (22.6%), erythromycin-sulfisoxazole (11.8%) and a first generation cephalosporin (10.2%) . The average duration of antibiotic therapy was 6.9 +/- 2.65 days . Specimens for bacterial cultures included 188 samples of middle ear fluid obtained by tympanocentesis and 37 collected from otorrhea fluid . RESULTS: One hundred forty-one samples (62.7%) from 126 children yielded 170 bacterial isolates . In 60 children (32.3%) the culture of the ear pus was sterile . Among the 170 bacterial isolates: 67 (39.4%) were Streptococcus pneumoniae (59 patients), of which 77.6% had reduced susceptibility to penicillin (PRSP with penicillin MIC > or = 0.125 mg/l); 61 (35.9%) were Haemophilus influenzae (56 patients) of which 49.2% were beta-lactamase producers; and 8 were Moraxella catarrhalis (8 patients), of which 87.5% were beta-lactamase producers . Thirty-six patients were infected by S . pneumoniae with penicillin MIC > or =1 mg/l . In our study attending day-care center (P = 0.04), temperature >38 degrees C with signs of otalgia (P = 0.02), age <2 years (P = 0.048) and prior antibiotic treatment with erythromycin-sulfisoxazole (P = 0.006) were independently predictive risk factors for patients infected with penicillin-resistant S . pneumoniae . Pneumococcal serogroups 23, 14 and 19 were predominant (25.4, 25.4 and 23.8%, respectively) . Penicillin resistance was mainly associated with serogroups 23 and 14 . CONCLUSIONS: Penicillin-resistant S . pneumoniae isolates are frequently responsible for therapeutic failure in cases of acute otitis media in the Paris region.

J Otolaryngol, 1998, 27 Suppl 2, 26 - 36
Medical therapy of otitis media: use, abuse, efficacy, and morbidity; Bitnun A et al.; OBJECTIVE: Otitis media (OM) is one of the most common paediatric disorders encountered by primary care physicians . Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are the principal pathogens responsible for OM . As a result of the increasing prevalence of antimicrobial resistance, the use of antimicrobial therapy in OM has come under close scrutiny . Amoxicillin remains the most appropriate option for initial empiric therapy of acute otitis media (AOM) . The duration of therapy required for AOM depends on the age of the patient, the severity of disease, and the route of administration . In most cases, particularly in children older than 5 years of age, a 5-day course of antibiotic therapy should suffice . Antibiotic therapy is not required in most cases of otitis media with effusion (OME) and should be reserved for those with bilateral effusions persisting for longer than 3 months associated with significant hearing loss . Antibiotic prophylaxis for recurrent AOM should be minimized . Myringotomy with or without tympanostomy tube placement is an important therapeutic option in those with OME and recurrent AOM . Active immunization against S . pneumoniae and Influenza A is likely to play an increasingly important role in the prevention of OM.

Chemotherapy, 1998 Sep, 44 Suppl 1, 19 - 23
Cefixime in the treatment of upper respiratory tract infections and otitis media; de Lalla F; An increasing number of clinical failures has been noted after treatment of upper respiratory tract infection and acute otitis media with conventional antibiotics . At present, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and group A beta-hemolytic streptococcus (GABHS) are the bacterial pathogens most frequently responsible for these infections . Although GABHS has so far not developed penicillin resistance, the frequency of bacteriological failures with either benzathine penicillin or penicillin V has increased . Firstly, a number of hypotheses have been put forward to explain this, including poor patient compliance and inactivation by beta-lactamase-producing oropharyngeal flora . Secondly, this has added to the demand for new agents to treat resistant streptococci . Cefixime, an orally active third-generation cephalosporin, has attracted considerable attention following the results of numerous clinical studies . Comparative studies between cefixime and conventional antibiotics for the treatment of upper respiratory tract infections and otitis media are summarized.

Chemotherapy, 1998 Sep, 44 Suppl 1, 1 - 5
Overview of the clinical features of cefixime; Adam D; Third-generation cephalosporins in oral formulations have become an increasingly important first-line choice against common bacterial infections . Cefixime is one such agent, which possesses excellent efficacy against a broad spectrum of pathogens, including Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis . Clinical success rates are similar to cefaclor, clarithromycin, and other cephalosporins . Importantly, cefixime also possesses excellent activity against beta-lactamase-producing strains . The pharmacodynamic features of the drug include a half-life of 3-4 h and a Cmax of 4.4 microg/ml, well above the MIC90 for susceptible pathogens, permitting once-daily dosing . In this brief overview, the bacteriological and clinical efficacy of cefixime is discussed, as well as its indications.

Can J Vet Res, 1998 Oct, 62(4), 262 - 7
The association of titers to Haemophilus somnus, and other putative pathogens, with the occurrence of bovine respiratory disease and weight gain in feedlot calves; Martin SW et al.; Serum samples were obtained from 602 calves (from 19 groups in four feedlots: three in Ontario, and one in Alberta) upon arrival at the feedlot and 28 d later . Of these calves, 202 developed bovine respiratory disease (BRD) and 400 did not develop BRD . Based on high antibody titers noted upon arrival, we infer that most calves were exposed to Haemophilus somnus prior to arrival at the feedlot . Within a group, calves with high titers on arrival had a reduced risk of developing BRD later . Most calves did not experience titer increases after arrival; however, calves that had stable or increasing titers had a relatively low risk of contracting BRD . The calves at greatest risk of BRD were those with titers on arrival of less than 6.8 units and subsequent titer decreases of more than 1 unit . The effects of both the titer on arrival and the titer change after arrival were stable when the serologic effects of a number of viruses and Mycoplasma agents were considered . Neither antibody titer on arrival nor titer change was related to weight gain differences among calves . Calves with BRD or calves with lower weight on arrival had decreased weight gains in the first 28-day feeding period . The high titers on arrival may have protected most calves against further infection with H . somnus . However, since the calves that developed BRD had large titer increases to a number of viruses and to Pasteurella haemolytica, while having decreased antibody titers to H . somnus, we infer that the existing antibodies were "used up" in combatting the agents, including H . somnus, which may have "caused" the BRD . Calves which were able to increase their antibody levels to H . somnus tended to have a reduced risk of BRD.

Can J Vet Res, 1998 Oct, 62(4), 251 - 6
Effect of porcine reproductive and respiratory syndrome virus infection on the clearance of Haemophilus parasuis by porcine alveolar macrophages; Solano GI et al.; Porcine reproductive and respiratory syndrome virus (PRRSV) infection in young piglets is frequently associated with secondary infection due to various pathogens, especially those of the respiratory tract . One of the most important mechanisms in respiratory diseases is related to the alteration of function of porcine alveolar macrophages (PAMs) . The objective of this study was to determine how PRRS virus infection affects the capabilities of PAMs in the phagocytosis and destruction of Haemophilus parasuis . Phagocytosis percentages were determined in vitro and ex vivo, after collected PAMs were directly exposed to the virus of if PAMs were collected from piglets previously infected with PRRSV . In vitro experiments demonstrated that H . parasuis uptake by PAMs is only increased in the early stages of PRRSV infection (2 h post-infection) . In contrast, in the ex vivo experiments it was shown that PAMs from PRRSV-infected piglets do not seem to change in their phagocytic rate until the later stages of infection . Together with a decrease in the phagocytic rate, a marked decrease in the functional ability of PAMs to kill bacteria was observed 7 d post-infection . It is hypothesized that when animals are exposed to PRRSV, there is a marked decrease in the functional ability of PAMs to kill bacteria through the release of superoxide anion, indicating a possible negative effect of the virus, at least at the macrophage level.

Antimicrob Agents Chemother, 1998 Nov, 42(11), 3032 - 4
Activity of HMR 3647 compared to those of five agents against Haemophilus influenzae and moraxella catarrhalis by MIC determination and time-kill assay; Pankuch GA et al.; The microdilution MICs of HMR 3647, erythromycin A, azithromycin, clarithromycin, roxithromycin, and pristinamycin against 50/90% of 249 Haemophilus influenzae and 50 Moraxella catarrhalis isolates were 2/4, 0.06/0.125; 8/16, 0.25/0.25; 2/4, 0.06/0.125; 16/16, 0.25/0.25; 32/>32, 1/2; and 2/4, 0.5/0.5 microg/ml . Azithromycin was bactericidal against all 10 H . influenzae and 3 of 5 M . catarrhalis isolates and HMR 3647, erythromycin A, clarithromycin, roxithromycin, and pristinamycin were bacteriostatic, against all 15 strains after 24 h at the MIC.

Antimicrob Agents Chemother, 1998 Nov, 42(11), 3000 - 1
Bacteriostatic and bactericidal in vitro activities of clarithromycin and erythromycin against periodontopathic Actinobacillus actinomycetemcomitans; Piccolomini R et al.; The susceptibilities of 87 periodontitis-associated strains of Actinobacillus actinomycetemcomitans to clarithromycin and erythromycin were determined by standard methodology recommended for Haemophilus influenzae . For clarithromycin the MIC at which 90% of the isolates were inhibited was </=2.0 microg/ml and the minimal bactericidal concentration at which 90% of the strains were killed was </=4.0 microg/ml, suggesting that it would be a candidate for therapeutic trials in patients with periodontitis.

Antimicrob Agents Chemother, 1998 Nov, 42(11), 2956 - 60
Activities of new fluoroquinolones against fluoroquinolone-resistant pathogens of the lower respiratory tract; Piddock LJ et al.; The activities of six new fluoroquinolones (moxifloxacin, grepafloxacin, gatifloxacin, trovafloxacin, clinafloxacin, and levofloxacin) compared with those of sparfloxacin and ciprofloxacin with or without reserpine (20 microg/ml) were determined for 19 Streptococcus pneumoniae isolates, 5 Haemophilus sp . isolates, and 10 Pseudomonas aeruginosa isolates with decreased susceptibility to ciprofloxacin from patients with clinically confirmed lower respiratory tract infections . Based upon the MICs at which 50% of isolates were inhibited (MIC50s) and MIC90s, the most active agent was clinafloxacin, followed by (in order of decreasing activity) trovafloxacin, moxifloxacin, gatifloxacin, sparfloxacin, and grepafloxacin . Except for clinafloxacin (and gatifloxacin and trovafloxacin for H . influenzae), none of the new agents had improved activities compared with that of ciprofloxacin for P . aeruginosa and H . influenzae . A variable reserpine effect was observed for ciprofloxacin and S . pneumoniae; however, for 9 of 19 (47%) isolates the MIC of ciprofloxacin was decreased by at least fourfold, suggesting the presence of an efflux pump contributing to the resistance phenotype . The laboratory parC (Ser79) mutant strain of S . pneumoniae required eightfold more ciprofloxacin for inhibition than the wild-type strain, but there was no change in the MIC of sparfloxacin and only a 1-dilution increase in the MICs of the other agents . For efflux pump mutant S . pneumoniae the activities of all the newer agents, except for levofloxacin, were reduced . Except for clinafloxacin, all second-step laboratory mutants required at least 2 microg of all fluoroquinolones per ml for inhibition.

Int J Clin Pract, 1998 Jul-Aug, 52(5), 289 - 97
Short-course cefuroxime axetil therapy in the treatment of acute exacerbations of chronic bronchitis; Langan C et al.; The efficacy and safety of a five-day course of cefuroxime axetil (250 mg b.d.) and a seven-day course of clarithromycin (250 mg b.d.) were compared in a large double-blind, randomised, multinational study involving 684 patients with acute exacerbations of chronic bronchitis . In an intent-to-treat analysis, the post-treatment clinical responses to each treatment were comparable (82%) and rates at follow-up were similar: 64% on cefuroxime axetil and 61% on clarithromycin . Pre-treatment pathogens were isolated from a total of 192 patients, Haemophilus influenzae being the most common . Overall pathogen eradication rates were similar for both treatments . Both treatments were well tolerated . In conclusion, a five-day course of cefuroxime axetil is clinically equivalent to a seven-day course of clarithromycin in the treatment of acute exacerbations of chronic bronchitis, and may have potential socioeconomic benefits.

Nippon Jibiinkoka Gakkai Kaiho, 1998 Sep, 101(9), 1093 - 8
{The role of IL-1 beta in murine model of otitis media with effusion}; Kurono Y et al.; Recent studies have demonstrated the presence of inflammatory cytokines such as IL-1 beta, TNF-alpha, IL-6, and IL-8 in the middle ear effusion (MEE) of patients with otitis media with effusion (OME) . IL-1 beta is known to be produced from macrophages and monocytes in an early stage of inflammation by stimulation with microorganisms and endotoxins . Also, these studies have shown that endotoxins frequently are found in MEE and can induce OME in experimental animal model . These findings suggest that endotoxins in MEE cause a chain reaction of cytokines through IL-1 beta . However, the precise role of IL-1 beta in the pathogenesis of OME has not yet been clarified . In the present study, a murine model of OME was developed by intra-tympanic injection with endotoxin or recombinant mouse IL-1 beta (rIL-1 beta) and the effects of IL-1 beta on the production of MEE were investigated . OME was induced in specific pathogen-free male BALB/c mice by intra-tympanic inoculation with endotoxin purified from nontypeable Haemophilus influenzae or with rIL-1 beta . The presence of MEE in the subjects was observed through the ear drum under a microscope and samples of MEE were collected by aspiration and washing with phosphate-buffered saline . The concentrations of IL-1 beta in each sample of MEE were determined by ELISA and the histological changes were compared . The mice inoculated with endotoxin showed signs of the production of MEE and it was noted that the levels of IL-1 beta in MEE were significantly increased on day 3 . Intra-tympanic inoculation with rIL-1 beta also produced MEE and these cytological findings of MEE as well as the histological findings of middle ear mucosa were similar to those found in the endotoxin-induced OME . Further, the influence of anti-IL-1 receptor antibodies on the production of OME was examined 3 days after intra-tympanic injection with anti-IL-1 receptor antibodies together with endotoxin or rIL-1 beta . The incidence of OME was lower in mice injected with anti-IL-1 receptor antibodies than that in mice injected with endotoxin or rIL-1 beta only . These findings suggest that IL-1 beta may play an important role in the pathogenesis of OME.

Vaccine, 1998 Dec, 16(20), 1976 - 81
Assessment of the immunogenicity and reactogenicity of a quadrivalent diphtheria, tetanus, acellular pertussis and hepatitis B (DTPa-HBV) vaccine administered in a single injection with Haemophilus influenzae type b conjugate vaccine, to infants at 2, 4 and 6 months of age; Aristegui J et al.; This double-blind, randomised study was performed to assess the immunogenicity and reactogenicity of three lots of a quadrivalent diphtheria-tetanus-acellular pertussis-hepatitis B vaccine (DTPa-HBV) co-administered with three lots of Haemophilus influenzae type b conjugate (Hib) vaccine in one injection, as a primary vaccination course in healthy infants at 2, 4 and 6 months of age . 269 infants (8-11 weeks of age) were randomly allocated to three groups to receive DTPa-HBV/Hib vaccines, concomitantly with oral polio vaccine . Blood samples for antibody determinations were taken before vaccination and 1 month after the third dose in 262 subjects . Local and general symptoms were recorded by parents on diary cards . All vaccinees had post-vaccination protective anti-D and anti-T (> or = 0.1 IU ml-1) antibodies, and 98% had protective anti-HBs antibody titres (> or = 10 mIU ml-1) . There were no statistically significant differences between groups in post-vaccination anti-D, anti-T, anti-HBs antibody geometric mean titres (GMT), these being 3.49 IU ml-1, 5.92 IU ml-1 and 1109 mIU ml-1, respectively . All subjects responded to three pertussis components, i.e . pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (PRN) . Although statistically significant differences in GMTs of anti-PT, anti-FHA and anti-PRN were found between groups, these were not believed to be of any clinical relevance as the minimum GMTs were 60, 193 and 230 EL.U ml-1 for anti-PT, anti-FHA and anti-PRN, respectively . There were no statistically significant differences in anti-PRP antibody GMT (4.05 micrograms ml-1) between groups, 100% and 85% of subjects having titres > or = 0.15 and 1.0 microgram ml-1, respectively . No symptoms were reported for one third of the subjects . Fever (> 38 degrees C) was reported after 16% of doses, with < 1% having > 39.5 degrees C . Almost all local and general symptoms were mild or moderate, and lasted less than 48 h . No subject dropped out due to a severe adverse reaction . The administration of an experimental mix of DTPa-HBV and Hib vaccines in a single injection is safe, well-tolerated and immunogenic for all vaccine components.

Vaccine, 1998 Dec, 16(20), 1950 - 6
Specific mucosal immunity and enhanced nasopharyngeal clearance of nontypeable Haemophilus influenzae after intranasal immunization with outer membrane protein P6 and cholera toxin; Hotomi M et al.; Nontypeable Haemophilus influenzae (NTHi) is one of the leading pathogens in otitis media . Studies of vaccines against NTHi have focused on outer membrane proteins (OMPs) . One outer membrane protein P6 is highly conserved among strains and is an attractive candidate for a subunit bacterial vaccine . In this study, mucosal immunity induced by intranasal immunization with P6 and cholera toxin (CT) was investigated in a mouse model . Intranasal immunization with P6 and CT evoked a good mucosal IgA as well as a systemic IgG response against P6 . On the other hand, intranasal immunization with P6 alone induced a weak mucosal IgA response . Enzyme linked immunospot assay detected anti-P6 specific antibody producing cells in the nasopharyngeal mucosa of immunized mice . The protective response of intranasal immunization was demonstrated by enhancement of nasopharyngeal clearance of NTHi and inhibition of adherence of NTHi to cultured human epithelial cells . Based on these results, intranasal immunization with P6 and CT may be an effective approach to protect human from H . influenzae infections in the upper respiratory tract.

Vaccine, 1998 Nov, 16(19), 1885 - 97
Addressing the challenges to immunization practice with an economic algorithm for vaccine selection; Weniger BG et al.; The biotechnology revolution is producing a growing bounty of new vaccines which pose difficult choices in selecting among many products . Some major public and private purchasers of vaccine may offer individual physicians and clinics their choice in assembling vaccine inventories . Others might purchase only a limited stock of products that would satisfactorily immunize a typical child . In either case, current vaccine selection decisions are based principally on purchase price alone without systematic consideration of other factors of fiscal consequence . As a potential tool for decision making, we developed an economic algorithm for vaccine selection that would minimize the overall costs of disease control through immunization by considering: (1) purchase price, (2) number of doses needed, (3) preparation time, (4) route of administration, (5) cold storage needs, (6) shelf life, (7) earliest age of full immunity, (8) adverse events frequency, and (9) efficacy of protection . To demonstrate the algorithm, variables (1) to (4) above were incorporated into a pilot binary-integer linear programming model that satisfied the recommended immunization schedule for diphtheria, tetanus, pertussis, Haemophilus influenzae b, and hepatitis B, using eleven vaccines (DTaP, DTaP-Hib, Hib, HepB and Hib-HepB) from four manufacturers . Five (or six) opportunities to vaccinate were modeled at (1), 2, 4, 6, 12-18, and 60 months of life, assuming US$40 per clinic visit, $15 per injection, and $0.50 per minute of nurse preparation time . Vaccine costs were varied using actual March and September 1997 US Federal vaccine prices, as well as estimates for unpriced new vaccines . Over 16,000 distinct vaccine stocking lists by vaccine type and brand were possible . Including a 1-month visit, the lowest-cost 'solution' of the algorithm was $529.41 per child in the March cost-assumption case, and $490.32 in the September one (both included four doses of DTaP-Hib, three HepB, and one DTaP) . Without a 1-month visit, the lowest-cost solution in the March case cost $486.67 (four DTaP, two Hib-HepB, one DTaP-Hib, and one HepB), while the September case cost $450.32 (four DTaP-Hib, three HepB, and one DTaP) . Ensuring at least one product was selected from each of the four manufacturers increased costs about $13.00, and the needed injections rose from eight to nine . The most economical selection of vaccines to use cannot be intuitively predicted, as permutations are large and solutions are sensitive to minor changes in costs and constraints . A transparent, objective selection method that weighs the economic value of distinguishing features among competing vaccines might offer the 'best value' to vaccine purchasers, while also creating strong market incentives for continuing innovation and competition in the vaccine industry.

Vaccine, 1998 Nov, 16(19), 1842 - 9
Preclinical studies on a recombinant group B meningococcal porin as a carrier for a novel Haemophilus influenzae type b conjugate vaccine; Fusco PC et al.; In anticipation of future combination vaccines, a recombinant class 3 porin (rPorB) of group B meningococci was evaluated as an alternative carrier protein for a Haemophilus influenzae type b (Hib) polyribosylribotol phosphate (PRP) conjugate vaccine . The use of rPorB may avoid undesirable immunologic interactions among vaccine components, including epitopic suppression from conventional carriers (e.g . tetanus toxoid {TT}), as well as provide desirable immunomodulatory effects . Rats were found to be more reliable and consistent than mice or guinea pigs for studying antibody responses to the Hib conjugates . Different Hib conjugates, Hib-TT and Hib-rPorB, consisting of PRP conjugated by reductive amination to TT or rPorB, were compared in rats . Commercially available, licensed vaccines, HbOC (HibTITER) and PRP-T (OmniHib), were used as reference controls . Maximum geometric mean ELISA IgG titers were obtained in rats after only two doses, showing booster effects for all . However, Hib-rPorB immunization consistently resulted in responses that were 1-2 orders of magnitude greater than those for the other conjugates, including the licensed control vaccines . A maximum 4600-fold rise was observed for Hib-rPorB after two doses, and, unlike the other conjugates, a 100% response rate was always achieved without adjuvant . These results warrant further investigation of Hib-rPorB in combination with DTaP.

Rev Esp Quimioter, 1998 Sep, 11(3), 245 - 50
{Ampicillin-sulbactam activity against respiratory isolates of Haemophilus influenzae}; Cisterna R et al.; A study was conducted on the in vitro activity of ampicillin/sulbactam against 100 respiratory strains of Haemophilus influenzae (45 betalactamase positive and 55 betalactamase negative strains) simultaneously isolated during 1997 in 6 Spanish hospitals: Hospital Clinico San Carlos (Madrid), Hospital de Cruces de Basurto (Bilbao), Hospital La Fe (Valencia), Hospital Virgen Macarena (Seville), Hospital de Bellvitge (Barcelona) and Hospital Clinico Universitario (Salamanca) . It was studied in comparison to amoxicillin, amoxicillin/clavulanic acid, cefuroxime, clarithromycin and ciprofloxacin . The MIC breakpoints used for the interpretation of data were those published by the National Committee for Clinical Laboratory Standards in 1997 . All of the strains tested were susceptible to ampicillin/sulbactam, amoxicillin/clavulanic acid, cefuroxime and ciprofloxacin . The rate of resistance to clarithromycin was 55.5% for betalactamase positive strains and 38 . 2% for betalactamase negative strains . A total of 23.6% of the betalactamase negative strains were resistant or showed intermediate susceptibility to amoxicillin but were susceptible to betalactam/betalactamase inhibitor combinations and cefuroxime.

Rev Esp Quimioter, 1998 Jun, 11(2), 132 - 8
{Prospective and comparative study between cefuroxime, ceftriaxone and amoxicillin-clavulanic acid in the treatment of community-acquired pneumonia}; Sanchez ME et al.; Among community-acquired infections, pneumonia is still a large health problem which is of great interest mainly due its high mortality and morbidity . From 1991 to 1997, 409 patients who had been diagnosed with community-acquired pneumonia and had been admitted to the internal medicine service of a university hospital were prospectively studied . The patients were classified into three groups according to the random antibiotic treatment they had received (ceftriaxone, cefuroxime or amoxicillin-clavulanic acid) . The initial characteristics of the patients with regard to epidemiology, clinical description and critical situation were similar in all the groups studied . A total of 36.9% of the cases were documented microbiologically, with the most frequently isolated pathogens being Streptococcus pneumoniae and Haemophilus influenzae . The recovery rate was 92.2% and three patients had a recurrence of pneumonia . Global mortality was 5.8% . No statistically significant differences were found in the evolution of patients treated with cefuroxime, ceftriaxone or amoxicillin-clavulanic acid, with the latter representing an empirical treatment of choice for community-acquired pneumonia.

Rev Esp Quimioter, 1998 Mar, 11(1), 47 - 51
{In vitro activity of trovafloxacin in 238 respiratory pathogens.}; Alarcon T et al.; The in vitro activity of trovafloxacin against 238 clinical isolates obtained from respiratory specimens were compared with ciprofloxacin . Fifty-four Haemophilus influenzae, 58 Streptococcus pneumoniae, 40 Moraxella catarrhalis, 21 Streptococcus pyogenes, 25 Klebsiella pneumoniae and 40 Staphylococcus aureus (21 methicillin resistant and 19 methicillin susceptible) were studied . The MIC was determined following NCCLS recommendations . Ciprofloxacin and trovafloxacin MIC90 was 0.016 mg/l and 0.016 mg/l for H . influenzae, 4 mg/l and 0 . 25 mg/l for S . pneumoniae, </=0.008 mg/l and </=0.008 mg/l for M . catarrhalis, 0.5 mg/l and 0.064 mg/l for S . pyogenes, 0.064 mg/l and 0.25 mg/l for K . pneumoniae, 16 mg/l and 0.5 mg/l for methicillin-resistant S . aureus and 2 mg/l and 0.032 mg/l for methicillin-susceptible S . aureus . According to this data, trovafloxacin showed better in vitro activity than ciprofloxacin in the Gram-positive pathogen studied and similar activity against the Gram-negatives tested.

Presse Med, 1998 Sep 26, 27(28), 1440 - 1
{Would ampicillin alone again be enough for treating community-acquired pneumonias?}; Bedos JP; MORE THAN SEMANTICS: The complexity of the problem raised by this apparently simple question becomes apparent if one examines the meanings behind the words . STILL SUFFICIENT: Globally, the frequency of pathogens known to cause community-acquired pneumonia has changed little over time: Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumoniae . The real question is the emergence of S . Pneumoniae resistant strains . Currently, the frequency of penicillin or ampicillin resistant strains (less then 10%) is not associated with an increased rate of treatment failure or mortality . "High" doses (150-200 MU/kg/d for penicillin or 2 g t.i.d . for ampicillin) can still be expected to control suspected or certain resistant pneumococcal pneumonia . STILL SUFFICIENT: Would other antimicrobials be more effective? In France, "consensual" use of amoxicillin (1 g t.i.d.) "covers" 98% of the situations as resistant strains are found in only 2% of the adult cases . Thus, the lower frequency of pneumococcal resistance to cefotaxime or ceftriaxone (less than 0.5%) would not warrant their use in most cases of community-acquired pneumococcal pneumonia . Inversely, combination regimens with ampicillin or amoxicillin and cefotaxime or ceftriaxone or the amoxicillin-clavulanic acid association at standard doses provide good therapeutic alternatives for empirical prescriptions in cases with a high risk of infection other than pneumococcal infection (H.influenzae, methicillin-sensitive Staphylococcus aureus) . The remarkable anti-pneumococcal activity of imipenem, vancomycin and teicoplanin should, for the time being, be reserved for selected patients with cross allergic reactions to penicillins and cephalosporins . EMPIRICAL REGIMENS: In case of severe community-acquired pneumonia, a combination regimen should be the rule in order to "cover" as many bacteria as possible . In the "healthy" adult under 60 years of age, amoxicillin combined with a macrolide or a fluoroquinolone can be recommended . OUTLOOK: Bacteriological efficacy is not synonymous with cure . Secondary inflammatory processes and subsequent septic shock remain a major challenge.

Chest, 1998 Oct, 114(4), 1129 - 36
Pulmonary infiltrates in the surgical ICU: prospective assessment of predictors of etiology and mortality; Singh N et al.; A prospective cohort study of 129 consecutive patients developing pulmonary infiltrates in the surgical ICU was conducted to determine the predictors and outcome of pulmonary infiltrates . Most common etiologies of pulmonary infiltrates were pneumonia (30%), pulmonary edema (29%), acute lung injury (15%), and atelectasis (13%) . Enteral nutrition was associated with a significantly lower incidence of acute lung injury as compared with pneumonia (22% vs 58%, p = 0.012) . Patients with liver disease were significantly more likely to have pulmonary infiltrates due to acute lung injury as compared with other etiologies (p = 0.02) . Clinical pulmonary infection score (Pugin score) > 6 virtually excluded acute lung injury, pulmonary edema, or atelectasis as etiologies of pulmonary infiltrates . Nosocomial Haemophilus/pneumococcal pneumonia occurred significantly earlier in the ICU as compared with Gram-negative (p = 0.05) or methicillin-resistant Staphylococcus aureus pneumonia (p = 0.01) . Pneumonia in trauma patients was significantly more likely to be due to Haemophilus/pneumococcus as compared with all other ICU patients (54% vs 0%, p = 0.0004) . These data have implications for treatment of patients with nosocomial pneumonia in the ICU.

Diagn Microbiol Infect Dis, 1998 Sep, 32(1), 45 - 50
BAY 12-8039, a novel fluoroquinolone . Activity against important respiratory tract pathogens; Biedenbach DJ et al.; BAY 12-8039 or moxifloxacin is a new 8-methoxyquinolone with documented, improved activity against Gram-positive cocci and anaerobic bacteria . This study tested 1250 commonly isolated respiratory tract pathogens (251 Moraxella catarrhalis, 499 Haemophilus influenzae, 500 Streptococcus pneumoniae) from 1996-1997 clinical infections at more than 30 medical centers . Among the M . catarrhalis strains (81% beta-lactamase-positive) the BAY 12-8039 MIC90 was 0.06 microgram/mL, a potency equal to ofloxacin but less than all other tested fluoroquinolones (ciprofloxacin, clinafloxacin, levofloxacin, sparfloxacin, trovafloxacin) . The H . influenzae strains were generally less susceptible to BAY 12-8039 (MIC90, 0.03 microgram/mL) than the tested fluoroquinolones, and the other comparison compounds were less active overall . All S . pneumoniae strains were susceptible to BAY 12-8039 at < or = 0.25 microgram/mL (MIC90, 0.06-0.12 microgram/mL), a value equal-potent to trovafloxacin . This new fluoroquinolone, BAY 12-8039, appears promising for the treatment of community-acquired respiratory tract infections caused by common bacterial species.

Diagn Microbiol Infect Dis, 1998 Sep, 32(1), 27 - 32
Haemophilus influenzae meningitis in adults; Tang LM et al.; Haemophilus influenzae meningitis is rare in adults . We reviewed the microbiological records of cerebrospinal fluid (CSF) and blood cultures and the medical records of patients with bacterial meningitis admitted to Chang Gung Memorial Hospital from January 1978 to May 1996 . Haemophilus influenzae meningitis was found in six adult patients, accounting for 1.8% of 326 bacteriologically proven adult cases of meningitis diagnosed between January 1984 and May 1996 . Predisposing conditions included head trauma and/or neurosurgical procedure in four patients and an extracranial extension of a pituitary adenoma in a diabetic patient . None of them had altered consciousness on the day of treatment . A CSF cell count less than 500 x 10(6) leukocytes/liter was noted in three patients . Antibiotic therapy was successful in all patients . Thus, predisposing conditions, particularly head trauma and/or neurosurgical procedure, are commonly present in adult patients with H . influenzae meningitis . Patients with the infection may have a low cellular count in the CSF that may be readily misinterpreted as meningitis caused by other pathogens.

Diagn Microbiol Infect Dis, 1998 Sep, 32(1), 15 - 9
Antigenuria in Gambian infants following immunization with a Haemophilus influenzae type b polyribosylribitol phosphate-tetanus toxoid protein conjugate (PRP-T) vaccine; Adegbola RA et al.; During a Haemophilus influenzae type b (Hib)-conjugate vaccine trial, the prevalence and duration of antigenuria after vaccination was studied in 102 Gambian infants aged 51 to 175 days . Urine samples were collected at 0, 1, 3, 7, 14, 21 and 28 days postvaccination and tested for Hib antigen by latex agglutination using Biomerieux and Directigen reagent kits . Biomerieux positive reactions were found in 6 of 247 (2.4%) samples from vaccinated children and in 8 of 199 (4.0%) from nonvaccinated children (chi 2 = 0.47; 1 df; p = 0.5) . In contrast, Directigen positive reactions were obtained with 86/242 samples (35.5%) from vaccinated children and from 28/190 (14.7%) from non-vaccinated children (chi 2 = 22.7; 1 df; p < 0.0001) . The highest rate of antigenuria was detected in samples collected on Day 7 after vaccination when 24 of 30 (80%) were positive . Antigenuria following vaccination was frequent and may complicate the use of this test as a means of diagnosing invasive Hib disease in vaccinated children.

Antibiot Khimioter, 1998, 43(9), 19 - 23
{Clinical significance of fungal and microbial associations and antibacterial therapy for treatment of chronic inflammatory respiratory tract diseases in children}; Platonova MM et al.; Microbiological examination applied to 270 children with chronic inflammatory and relapsing respiratory tract diseases revealed that by the frequency of the etiologically significant organisms the main pathogens isolated from the bronchial secretion belonged to Haemophilus influenzae, then followed Streptococcus pneumoniae and the less frequent isolates belonged to Branhamella catarrhalis characterized by high susceptibility to the 2nd and 3rd generation cephalosporins, erythromycin and azithromycin . Mycological investigation of the oral mucus and sputum from the patients revealed high frequency of Candida, mainly C.albicans . The fungi were most frequent and abundant in the children with chronic pulmonary diseases and congenital immune deficiency and in the children with bronchial asthma and asthmatic bronchitis, as well as in the children with exacerbation of the chronic disease, especially with bronchial obstruction . The antibacterial therapy with semisynthetic penicillins, cephalosporins and macrolides led to an increase in the number of the Candida carriers and in the biological material contamination level . The fungal contamination of the host was mainly observed after the use of the penicillins and cephalosporins . Chronic Candida carriers were detected among the patients with chronic inflammatory diseases of the lungs . The diseases in such patients were particularly severe . There were also detected children with colonization resistance to Candida . In the latter cases the chronic process was more favourable . The data made it possible to recommend a more differential use of the antibacterial and antimycotic drugs in the treatment of children with chronic inflammatory diseases of the bronchopulmonary system.

Arch Pediatr, 1998 Sep, 5(9), 1036 - 40
{Immunization schedule in the European Union}; Ovetchkine P et al.; All nations that are part of the European Union share the same aim for the control and eradication of vaccine-preventable diseases . However, there are differences in child immunization strategies and schedules between nations, depending upon health care systems, immunization habits and epidemiology of infectious diseases . All nations immunize children against diphtheria, tetanus, poliomyelitis, measles, rubella and mumps . Immunization against pertussis, Haemophilus influenzae, hepatitis B and tuberculosis are not systematically applied.

Berl Munch Tierarztl Wochenschr, 1998 Sep, 111(9), 321 - 5
{Determination of C-reactive protein and neopterin in serum of diseased and bacterially infected swine}; Schrodl W et al.; The parameters C-reactive protein (CRP) and neopterin, which are associated with immunological reactions, were investigated in serum of healthy, diseased and with Haemophilus parasuis infected pigs . When comparing diseased young pigs with healthy young pigs significant increases of the CRP- and neopterin concentrations can be seen . The increase of the CRP-concentration was most remarkable . After the infection of SPF-piglets with Haemophilus parasuis, significantly decreased neopterin concentrations and increased CRP concentrations were determined in comparison with non-infected animals . The animals with the symptoms of arthritis and disorders of the central nervous system showed the lowest neopterin concentrations and the highest concentrations of CRP . It seems that CRP and neopterin are interesting serum parameters in pigs with regard to the recognition of immunological reactions after illness or infection.

Cent Eur J Public Health, 1998 Aug, 6(3), 225 - 30
Analysis of bacterial meningitis during 1992-1996 in Poland; Tyski S et al.; Retrospective study of bacterial meningitis cases was performed by analysis of filled questionnaires received from 38 different hospitals located in 27 out of 49 provinces of Poland . Obtained data allowed to indicate that S . epidermidis, N . meningitidis, S . pneumoniae and H . influenzae were the most common bacterial strains isolated from cerebrospinal fluid of meningitis patients during the last five years . Besides data analysis performed, some strains of N . meningitidis (n = 97), H . influenzae (n = 28) and S . pneumoniae (n = 39) isolated from cerebrospinal fluid of meningitis patients hospitalized in different places in Poland sent by cooperating hospital laboratories (1995-1996), were phenotypically characterized . Neisseria meningitidis B:22:P1.14 was the most common isolate phenotype during the investigated time period . Streptococcus pneumoniae of twenty different serological types were isolated . Type 1 was the dominant--18% of strains . All but one Haemophilus influenzae strains isolated from cerebrospinal fluid belonged to serological type b . Biotyping showed presence of only two types: I and II, 39.3% and 60.7% of isolates respectively . The sensitivity of collected strains to selected antimicrobial agents (penicillin, cefotaxime, ceftriaxone, sulphametoxazol, chloramphenicol, tetracycline, ciprofloxacin, rifampin and erythromycin) used in treatment and prophylaxis of bacterial meningitis was investigated . Minimum inhibitory concentrations were determined by agar dilution method or with the use of E-tests . All investigated strains but one N . meningitidis, were not resistant to penicillin (MIC < or = 1 microgram/ml).

Ear Nose Throat J, 1998 Sep, 77(9), 748 - 9, 752-3, 757-8 passim
Mucosal immunity and bacteriology of the eustachian tube; Sorensen CH et al.; The pathogenesis of otitis media is a multifaceted process that is not completely understood . Eustachian tube dysfunction plays a central but uncertain role, as do viral and bacterial microorganisms . Of the latter, the three most important are Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis . This article reviews the various mechanisms of infection and the immune system's response to them.

Ophthalmology, 1998 Oct, 105(10), 1902 - 5; discussion 1905-6
Preseptal and orbital cellulitis in childhood . A changing microbiologic spectrum; Donahue SP et al.; OBJECTIVE: The authors sought to determine whether the microbiologic spectrum of preseptal and orbital cellulitis had changed over the past decade . DESIGN: A retrospective chart review of all inpatient and outpatient children with an ICD-9 diagnosis of preseptal or orbital cellulitis seen at Vanderbilt University Medical Center since the introduction of the Haemophilus influenzae type-B (HiB) vaccine (1986-1996) . MAIN OUTCOME MEASURES: Blood and abscess cultures from children with preseptal and orbital cellulitis were tabulated . RESULTS: During this period, 70 cases of preseptal cellulitis were seen . Blood cultures were obtained in 59 cases; only 6 were positive . Five cultures grew Streptococcus species . The one positive H . influenzae culture occurred in 1987 in a child who did not receive the HiB vaccine . There have been no new patients with preseptal cellulitis and H . influenzae bacteremia at Vanderbilt for 10 years . There were ten cases of orbital cellulitis, of which blood or abscess or both were cultured in eight . Six cases had positive cultures . Four cultures grew Streptococcus species . The other two grew H . influenzae and mixed H . influenzae/gram-positive cocci . CONCLUSION: The incidence of hemophilus-associated bacteremia in patients with preseptal cellulitis has decreased dramatically over the past 10 years . Streptococcus species now are the predominant cause . Orbital cellulitis due to H . influenzae may still occur, but it is much less likely . A more conservative approach to the diagnosis and management of preseptal and orbital cellulitis may be warranted.

Monaldi Arch Chest Dis, 1998 Jun, 53(3), 262 - 7
Airways microbial flora in COPD patients in stable clinical conditions and during exacerbations: a bronchoscopic investigation; Pela R et al.; Patients affected with chronic obstructive pulmonary disease (COPD) undergo frequent exacerbations of their illness characterized by increased cough and expectoration . The precise aetiology of these episodes often remains unknown . In the absence of clinical or radiographic signs of pneumonia, bacterial or viral cultures of sputum usually provide little useful information . Thus, we performed fibreoptic bronchoscopy using a protected specimen brush (PSB) to obtain uncontaminated secretions for culture from 56 patients with COPD, 16 with stable clinical conditions and 40 affected with exacerbations of the disease . The aim of our study was to evaluate bronchial microbial flora by quantitative aerobic and anaerobic culture of each specimen . Twenty five subjects (45%), 4 (16%) in stable state and 21 (84%) with COPD exacerbations, had specimens which gave rise to significant bacterial growth (> 10(3) colony forming units.mL-1) . The predominant bacteria were Streptococcus pneumoniae (in 10 cases) and alpha-haemolytic streptococci (in 6 cases); other bacteria found were coagulase-negative staphylococci and Branhamella catarralis in (2 cases each), and Proteus mirabilis, Haemophilus influenzae, Pseudomonas aeruginosa, Aerococcus viridans and Chromobacterium violaceum (each in a single case only) . Although significant bacterial growth was more frequently found in patients with chronic obstructive pulmonary disease exacerbations and in those with a higher degree of bronchial inflammation, the differences between the two groups of patients were not statistically significant . Nevertheless, the results obtained in our study confirm the validity of and the need for reliable sampling methods (like the protected specimen brush) to demonstrate significant bacterial colonization of the airways in chronic obstructive pulmonary disease patients.

Am J Health Syst Pharm, 1998 Sep 15, 55(18), 1881 - 97; quiz 1932-3
Otitis media: focus on antimicrobial resistance and new treatment options; Hoppe HL et al.; Antimicrobial resistance among organisms that cause acute otitis media (AOM) and new approaches in the prevention and treatment of AOM are discussed . Organisms commonly responsible for causing AOM include Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis . The evolution of pneumococcal resistance to penicillins, erythromycin, trimethoprim-sulfamethoxazole, and oral cephalosporins may require treatment with agents such as vancomycin or rifampin in certain patients . H . influenzae and M . catarrhalis are becoming increasingly resistant to penicillins, trimethoprim-sulfamethoxazole, oral cephalosporins, and macrolides . Mechanisms of resistance include changes in penicillin-binding proteins, production of beta-lactamase, alterations in target enzymes, and inhibition of drug access to the site of action . Because of changing resistance patterns and the limited spectra of activity of many currently available antimicrobials, new antimicrobials have been developed in the hope of improving therapy . While amoxicillin and trimethoprim-sulfamethoxazole are appropriate first-line agents, children at risk for resistant infections may be treated initially with cefuroxime axetil, cefpodoxime proxetil, cefprozil, or amoxicillin-clavulanate . After local resistance patterns, patient adherence to therapy, in vitro data, and cost factors have been weighed, other agents to consider include loracarbef, clarithromycin, azithromycin, and ceftriaxone . Along with the efforts to improve treatment, research is focusing on the prevention of otitis media with bacterial and viral vaccines . The emergence of resistant strains of organisms causing AOM has complicated its treatment.

Infect Immun, 1998 Nov, 66(11), 5450 - 6
Murine immune responses to Neisseria meningitidis group C capsular polysaccharide and a thymus-dependent toxoid conjugate vaccine; Rubinstein LJ et al.; The polysaccharide (PS) capsules of many pathogenic bacteria are poor immunogens in infants and young children as a result of the delayed response to PS antigens during ontogeny . The development of polysaccharide-protein conjugate vaccines for Haemophilus influenzae type b, which have proven to be efficacious in this age group, has led to active development by a number of investigators of conjugate vaccines for other diseases . We describe here the response of several mouse strains to the capsular PS of Neisseria meningitidis group C (MCPS) conjugated to tetanus toxoid (MCPS-TT) and the same response in BALB/c mice as a model of the immune consequences of conjugate vaccine immunization . The use of a conjugate vaccine results in a shift in the isotype elicited in response to the MCPS, from immunoglobulin M (IgM) and IgG3 to primarily IgG1 . A response to MCPS-TT is seen even among mouse strains which respond poorly to MCPS itself, emphasizing the importance of a strain survey when choosing a mouse model for a vaccine . The marked increase in IgG1 antibody titer was accompanied by a large increase in bactericidal activity of sera from these animals . Animals primed with the conjugate vaccine demonstrated a booster response after secondary immunization with either the MCPS or the conjugate . The ability to produce a boosted IgG1 anti-MCPS response to the MCPS can be transferred to adoptive recipients by B cells alone from mice primed with MCPS-TT but not mice primed with MCPS alone . These data indicate that in BALB/c mice a single immunization with MCPS-TT is sufficient to induce a shift to IgG1 and generate a memory B-cell population that does not require T cells for boosting.

Microbiology, 1998 Sep, 144 ( Pt 9), 2531 - 8
Cloning of the haemocin locus of Haemophilus influenzae type b and assessment of the role of haemocin in virulence; Murley YM et al.; The bacteriocin haemocin (HMC) is produced by most type b strains of Haemophilus influenzae, including strains determined to be genetically diverse, and is toxic to virtually all non-type b strains of H . influenzae, both encapsulated and non-encapsulated . Examination of the deduced amino acid sequences of several genes upstream of the previously identified HMC immunity gene (hmcI) revealed several features common to class II bacteriocins of certain Gram-positive bacteria . Mutagenesis of the open reading frame immediately upstream of hmcI resulted in a loss of the HMC production phenotype . When an HMC-producing strai of H . influenzae and the HMC-deficient isogenic mutant were compared for invasion on the infant-rat model, the HMC-producing strain was found to invade significantly earlier; however, a significantly higher number of rats infected with the isogenic mutant became bacteraemic as compared with those infected with the HMC-producing parent.

Microbiology, 1998 Sep, 144 ( Pt 9), 2525 - 30
An in silico evaluation of Tn916 as a tool for generalized mutagenesis in Haemophilus influenzae Rd; Hosking SL et al.; The transposon Tn916 was evaluated as a tool for generalized mutagenesis of the genome of Haemophilus influenzae . This was achieved in silico by searching the genome sequence of H . influenzae Rd for the published Tn916 target site consensus sequence 5' TT/ATTTT(N)6AAAAAA/TA . This search identified 16 putative target sites . In subsequent experiments, integration of Tn916 did not occur at any of these sites . Using the nucleotide sequences of these observed integration sites, a new consensus sequence, 5' TTTTT(N)xAAAAA (4 < or = x < or = 7), was derived . This sequence reflects the curve-twist-curve DNA topology which is a feature common to all Tn916 integration sites . A search of the H . influenzae Rd genome using the new consensus sequence identified 167 potential target sites, representing approximately 1% of the total genome . Only 80 of these sites were located within ORFs . The presence of such a limited number of target sites places severe constraints on the use of Tn916 as a tool for generalized mutagenesis of the genome of H . influenzae.

Otolaryngol Head Neck Surg, 1998 Oct, 119(4), 357 - 60
Sinusitis in neurologically impaired children; Brook I et al.; The microbiologic features of infected sinus aspirates in nine children with neurologic impairment were studied . Anaerobic bacteria, always mixed with aerobic and facultative bacteria, were isolated in 6 (67%) aspirates and aerobic bacteria only in 3 (33%) . There were 24 bacterial isolates, 12 aerobic or facultative and 12 anaerobic . The predominant aerobic isolates were Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus (2 each) and Proteus mirabilis, Pseudomonas aeruginosa, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae (1 each) . The predominant anaerobes were Prevotella sp . (5), Peptostreptococcus sp . (4), Fusobacterium nucleatum (2), and Bacteroides fragilis (1) . Beta-lactamase-producing bacteria were isolated from 8 (89%) patients . Organisms similar to those recovered from the sinuses were also isolated from tracheostomy site and gastrostomy wound aspirates in five of seven instances . This study demonstrates the uniqueness of the microbiologic features of sinusitis in neurologically impaired children, in which, in addition to the organisms known to cause infection in children without neurologic impairment, facultative and anaerobic gram-negative organisms that can colonize other body sites are predominant.

Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S207 - 10
Characterization of immune response as an indicator of Haemophilus influenzae type b vaccine efficacy; Madore DV; Quantitation of antibodies to Haemophilus influenzae type b (Hib) polysaccharide has been an active area of investigation associated with the development of polysaccharide and subsequently polysaccharide-protein conjugate vaccines . These clinical studies indicate that there are several serologic parameters associated with Hib vaccine efficacy in infants . Efficacious vaccines elicit polysaccharide-specific antibodies in infants; they prime the immune system for an anamnestic response; the immune response is long-lived through the period of greatest risk for disease; and the elicited antibodies have functional activity as demonstrated in bactericidal and opsonophagocytic assays or protection in an infant rat challenge model . The immune response to different Hib vaccines varies both quantitatively and qualitatively . With the introduction of routine Hib vaccine immunization, vaccine performance can rely on these serologic parameters . Quantitative serologic assays, the radio-antigen binding and enzyme-linked immunosorbent assays, have been developed and standardized . The quality of the antigen as well as optimization of all assay steps and reagents are key to ensuring specific and reproducible antibody quantitation.

Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S204 - 7
Enhanced surveillance of invasive Haemophilus influenzae disease in England, 1990 to 1996: impact of conjugate vaccines; Slack MP et al.; We report an enhanced prospective survey of invasive Haemophilus influenzae infections that has defined the pattern of invasive disease in five English regions for 2 years before and 4 years after the introduction of the H . influenzae type b (Hib) vaccination program . During the prevaccination period the majority of cases of invasive H . influenzae were caused by type b; most (89%) of these infections occurred in children <5 years of age and the most common presentation was meningitis . Since the introduction of routine immunization of infants with conjugate Hib vaccine, there has been a 16-fold reduction in the annual attack rate of invasive Hib disease recorded in children <5 years of age . This reduction is of a magnitude similar to that observed in other countries with Hib vaccination programs . The number of infections caused by non-type b H . influenzae has shown a small but progressive increase over the same period, emphasizing the need for continued surveillance . There was no increase in the number of infections caused by other serotypes . Diagnostic category varied with both age and serotype but was not affected by vaccine introduction; meningitis was the most common presentation overall but pneumonia and bacteremia were more common in adults and with noncapsulated isolates.

Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S198 - 203
A nationwide prospective surveillance study in Israel to document pediatric invasive infections, with an emphasis on Haemophilus influenzae type b infections . Israeli Pediatric Bacteremia and Meningitis Group; Dagan R et al.; BACKGROUND AND METHODS: An ongoing nationwide prospective surveillance study was initiated in Israel in October, 1988, to document childhood invasive infections caused by Haemophilus influenzae type b (Hib), Streptococcus pneumoniae and Neisseria meningitidis . This study enabled us to document the effect on childhood invasive Hib disease of the introduction of conjugate Hib vaccines to Israel . RESULTS: The incidence of invasive Hib disease before the age of 5 years dropped from 34 per 100000 before initiation of immunization to < 5 per 100000 in 1995 and is projected to be <4 in 1996 . After <2 years, when various conjugate vaccines had been available in the private sector alone and had achieved partial coverage only, the Israeli Ministry of Health decided to add Hib conjugate vaccine to the regular infant immunization program, free of charge, effective for all infants born after January 1, 1994 . The vaccine chosen was Hib polysaccharide linked to outer membrane protein complex of N . meningitidis B . Vaccine coverage has exceeded 90% of all infants born since January 1, 1994 . Efficacy and effectiveness during the first 34 months of the program (January 1, 1994, to October 31, 1996) were 95.4 and 99.7%, respectively, for all invasive Hib disease and 97 and 99.4%, respectively, for Hib meningitis . CONCLUSION: The described ongoing surveillance program showed the existence and extent of Hib problems in Israel and documented the success of the immunization program in essentially eliminating the disease in Israel.

Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S195 - 8
The rationale for population-based surveillance for Haemophilus influenzae type b meningitis; Levine OS et al.; Although Haemophilus influenzae type b (Hib) conjugate vaccines have been spectacularly successful, nearly eradicating Hib disease in countries where used routinely, they are relatively expensive . In many countries the incidence of Haemophilus influenzae type b (Hib) disease is uncertain, and it is unclear whether the local burden of Hib disease warrants the costs of adding Hib vaccine to the routine immunization program . Population-based surveillance to assess the local burden of Hib disease can help decision makers with this process . Although pneumonia is more common than meningitis, surveillance for Hib meningitis and invasive disease is likely to be more feasible and efficient than surveillance for Hib pneumonia . Standardization of laboratory methods for the isolation and identification of H . influenzae from CSF specimens is essential to successful surveillance . Should a country decide to introduce Hib conjugate vaccine as a routine immunization, population-based surveillance data collected before and after the introduction of vaccine can be used to monitor its impact . Finally population-based surveillance for bacterial meningitis also can provide information on the incidence of pneumococcal and meningococcal infections and on serogroup or serotype distributions that will be important when evaluating the new vaccines for those pathogens that are being developed.

Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S192 - 4
The etiology of bacterial pneumonia and meningitis in Vietnam; Tran TT et al.; BACKGROUND: To date no studies on the incidence of Haemophilus influenzae type b (Hib) disease, Hib carrier rates in infants and children or the proportion of bacterial meningitis cases caused by Hib in Vietnam have been performed . The availability of safe and highly effective Hib vaccines makes such information important . METHODS: The bacterial etiology of a sample of infants and children with pneumonia and meningitis seen at Pediatric Hospital No . 1 in Ho Chi Minh City was studied by culture and latex agglutination of blood, cerebrospinal fluid, urine and pleural fluid . The carriage rate of pneumococci and Hib was studied in a sample of outpatient children . RESULTS: Hib caused 53% of 34 culture-proven bacterial meningitis cases and pneumococci caused 18% . Of 31 meningitis cases diagnosed by latex agglutination, 39% were caused by Hib and 55% by pneumococci . Ninety percent of cases of Hib meningitis occurred in children <1 year of age . Fifty percent of meningitis cases were associated with acute respiratory infection . In 213 bacteremic pneumonia cases 92.5% of blood cultures grew Streptococcus pneumoniae and only 1% grew Hib . The carrier rate of Hib in outpatients <5 years of age with upper respiratory tract infection increased from 2% to 7.6% between 1993 and 1996 . CONCLUSION: Hib is the most frequent cause of meningitis in infants and children admitted to hospitals in South Vietnam . Ninety percent of Hib meningitis cases occur in patients < 1 year of age . Bacteremic Hib pneumonia in Vietnam is rare . The results suggest that Hib is the major cause of meningitis in Vietnam but do not permit conclusions regarding its true incidence . The carrier rate of Hib in children <5 years of age in Vietnam has increased to approximately 7% since 1993.

Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S189 - 90
Haemophilus influenzae meningitis in Malaysia; Hussain IH et al.; OBJECTIVE: To determine the pattern of postneonatal childhood meningitis in Malaysia . METHODS: Retrospective cross-sectional study involving five pediatric departments in Malaysia . RESULTS: There were 435 cases of clinical meningitis admitted to the five centers . More than 90% of the patients were <5 years old, and one-half were <6 months of age . The estimated overall incidence of childhood meningitis in the first 5 years of life was 76.7 per 100000 per year . However, of the 435 cases only 71 (16.3%) fulfilled laboratory diagnostic criteria and in only 58 of these was an organism isolated . Nearly one-half (48%) of all bacteriologically proved cases were caused by Haemophilus influenzae type b (Hib) . The mortality rate was 12.5% and 21 patients (30%) suffered neurologic sequelae . CONCLUSIONS: More than one-half of all cases of culture-positive childhood bacterial meningitis were caused by Hib, although successful isolation of a pathogen occurred in only a small proportion of cases . For this reason the true incidence of Hib meningitis in Malaysia remains unknown . These findings are consistent with previous studies in Malaysia.

Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S185 - 9
Epidemiology of systemic Haemophilus influenzae disease in Korean children; Lee HJ; BACKGROUND: There is a wide variation in the incidence and clinical characteristics of invasive infections by Haemophilus influenzae type b (Hib) among different populations . Characterizing the clinical significance in a particular community is essential for the development of vaccine policy . Data on the clinical significance of Hib in Asian children, including epidemiology and clinical spectrum, are quite limited . OBJECTIVE: To characterize invasive H . influenzae infections in Korean children in terms of clinical spectrum and frequency as an etiologic agent of bacterial meningitis and to review literature that may be helpful in understanding the epidemiology of H . influenzae disease in Far East Asian children, including Koreans . METHODS: Invasive infections by H . influenzae, Streptococcus pneumoniae and Neisseria meningitidis diagnosed at the Seoul National University Children's Hospital from 1986 to 1996 were reviewed . Conventional culture and the latex particle agglutination test were used in addition for diagnosis . A detailed literature review was undertaken to trace relevant information that may be helpful in understanding the epidemiology of invasive Hib disease among Far East Asian children . RESULTS: A total of 169 invasive infections were identified: 48 H . influenzae; 116 S . pneumoniae; and 5 N . meningitidis . Of the 48 H . influenzae infections 36 developed in apparently healthy children: 25 meningitis; 8 bacteremia; 2 pneumonia; and 1 epiglottitis . Forty-four percent of H . influenzae meningitis developed in infants < 1 year of age, and 92% occurred in children <5 years of age . H . influenzae was the cause of 58% of bacterial meningitis in infants and 62% in children <5 years old . CONCLUSION: The limited data suggest that the incidence of H . influenzae meningitis may be lower in Korean than in US children . Prospective population-based studies are needed urgently in Asian countries, including Korea.

Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S183 - 5
Childhood bacterial meningitis in Japan; Kamiya H et al.; Haemophilus influenzae type b (Hib) vaccines currently are not used in Japan, but interest in preventing H . influenzae disease by immunization has grown . We performed a retrospective survey for bacterial meningitis in 6 prefectures of Japan . Questionnaires requested the age, sex, clinical outcome and identity of the etiologic organism, if known, of all patients with meningitis younger than 16 years of age who were admitted during calendar year 1994 . Of 876 hospitals within the 6 study prefectures, 363 (41.4%) returned a completed questionnaire . There were 1769 cases of meningitis reported, of which 160 (9%) were considered bacterial in origin . H . influenzae was the most common cause of bacterial meningitis, accounting for 68 cases (43%) . Sixty-six cases (97%) of H . influenzae meningitis occurred in children 4 years of age or younger, and 27 (40%) occurred in children <1 year of age . Calculated incidence rates based on the population of children 4 years of age or less for each prefecture ranged from 3.4 to 9.9 cases per 100000 (mean, 4.7 cases/100000) . H . influenzae is the most common cause of meningitis in Japan, and the estimated incidence rates from this study are very similar to those previously reported from Japan . More comprehensive, prospective surveillance studies will be needed to define better the incidence of Hib meningitis and to aid in making rational decisions regarding the use of Hib vaccination in Japan.

Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S179 - 82
A population-based survey of Haemophilus influenzae type b nasopharyngeal carriage prevalence in Lombok Island, Indonesia; Gessner BD et al.; BACKGROUND: The Haemophilus influenzae type b (Hib) nasopharyngeal carriage prevalence and invasive disease incidence rates are unknown in Indonesia; consequently Hib vaccine is not included in the routine vaccine schedule . METHODS: To determine carriage prevalence we conducted a population-based, island-wide prospective study of a systematic sample of 484 children 0 to 2 years of age in Lombok, Indonesia . We conducted a risk factor questionnaire and determined serotypes and antibiotic sensitivity patterns . RESULTS: We identified 155 H . influenzae isolates, of which 22 were type b and 12 were encapsulated but not type b . The age- and population-weighted Hib carriage prevalence, adjusted for the sampling design, was 4.6% (95% confidence interval, 3.7 to 5.5%) . Children younger than 6 months of age had a carriage prevalence less than one-half that of older children, and carriage varied within the four administrative regions of the island; otherwise no risk factors for Hib carriage were identified . All Hib specimens were sensitive to ampicillin and 20 (91%) were sensitive to chloramphenicol . CONCLUSIONS: The Hib carriage prevalence in Lombok is similar to that found in developed countries before vaccine introduction . This suggests that further studies should proceed to determine whether Lombok has invasive disease rates as high as those that justified vaccine introduction in developed countries.

Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S176 - 8
Epidemiologic study of bacterial meningitis in Jakarta and Tangerang: preliminary report; Pusponegoro HD et al.; OBJECTIVE: To identify the cause of bacterial meningitis in children >1 month of age and <5 years of age in several hospitals in Jakarta and Tangerang, Indonesia . METHODS: Hospital-based, prospective surveillance study of 100 subjects between 1 month and 5 years of age . Subjects meeting inclusion criteria were evaluated for clinical and laboratory findings of bacterial meningitis . RESULTS: Of 16 subjects enrolled thus far, 11 have been diagnosed as bacterial meningitis . Of these 11, 6 had positive cerebrospinal fluid (CSF) cultures (2 with Haemophilus influenzae and one each with Neisseria meningitidis, Staphylococcus aureus, Klebsiella ozaenae and Escherichia coli) . Three of the 6 had positive latex agglutination tests (LAT; 2 H . influenzae and 1 N . meningitidis); LAT was negative for all 10 with negative CSF culture . CSF Gram-stained smear was positive only for the subject with E . coli . CONCLUSIONS: The number of children admitted with bacterial meningitis has been declining, perhaps because of early treatment with antibiotics in the community . Of culture-positive cases 33% have been caused by H . influenzae, but this result is based on few patients thus far . LAT has correlated well with culture, whereas Gram stain has had low sensitivity, perhaps reflecting deficiencies in technique.

Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S172 - 5
Invasive Haemophilus influenzae disease in India: a preliminary report of prospective multihospital surveillance . IBIS (Invasive Bacterial Infections Surveillance) Group; Steinhoff MC; OBJECTIVE: To determine the frequency, clinical characteristics and outcome of acute invasive infections caused by Haemophilus influenzae . DESIGN: Prospective hospital-based surveillance . SETTING: Six large academic referral hospitals in India . PARTICIPANTS: Three thousand four hundred forty-one patients from infancy to adulthood with pneumonia, meningitis or suspected bacterial sepsis . RESULTS: Preliminary data from 24 months of surveillance are presented . There were 58 H . influenzae isolates, of which 96% were serotype b . Nearly all isolates were from infants and children <5 years old, and most of the childhood isolates were from infants <1 year of age . Meningitis cases accounted for 69% of isolates . Overall case fatality was 11% . More than 50% of isolates were resistant to chloramphenicol, and up to 40% were resistant to ampicillin, trimethoprim-sulfamethoxazole or erythromycin . There was no resistance to third-generation cephalosporins . CONCLUSIONS: These preliminary data from six hospitals suggest a substantial burden of severe, preventable H . influenzae infections in India . The distribution of clinical syndromes and the ages of our Hib patients are fairly similar to data from North America and Europe.

Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S169 - 71
Haemophilus influenzae disease in children in India: a hospital perspective; John TJ et al.; We review and summarize published information on diseases caused by Haemophilus influenzae in India and unpublished data from our center covering more than three decades . Since the mid-1950s H . influenzae has been the most common cause of pyogenic meningitis in children admitted to our hospital, accounting for one-third to one-half of cases . Information from other centers in India has been scanty; the lower frequency of isolation of Haemophilus in studies in some centers may be caused by unsatisfactory media and culture methods . The annual numbers of admissions for pyogenic meningitis in our hospital have been quite similar to the numbers of cases of poliomyelitis . Assuming that the similar numbers of children hospitalized with these two diseases indicate similar incidence rates in the community and taking into account the frequency of Haemophilus isolations in pyogenic meningitis, we estimate that there may be as many as 75 to 100 cases of meningitis caused by this organism per year per 100000 children <5 years of age . Although pneumonia caused by H . influenzae has been recognized in a few studies, information is too scanty to attempt the estimation of incidence . Pus-producing infections caused by Haemophilus are rare . Epiglottitis caused by Haemophilus does not seem to occur in India . In recent years we have found that most invasive Haemophilus infections are caused by H . influenzae type b (Hib); other types or untypable strains are infrequent . An increasing prevalence of resistance to chloramphenicol and ampicillin has been recognized in our center and elsewhere . Thus from a hospital perspective, primary prevention by using Hib vaccine seems to be a rational and beneficial intervention . Community-based studies to measure the disease burden of Hib are urgently needed for a more satisfactory assessment of the need for, and cost benefit of, Hib immunization of all infants.

Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S165 - 9
Haemophilus influenzae type b infections in Hong Kong; Lau YL et al.; A 5-year territory-wide retrospective survey of invasive Haemophilus influenzae type b (Hib) diseases in Hong Kong established that the annual incidence for children <5 years old was 2.7 per 100000 {95% confidence interval (CI), 2.0 to 3.5} . However, the corresponding annual incidence in Vietnamese refugees in Hong Kong was 42.7 per 100000 (95% CI 17.2 to 87.9), giving a relative risk of 18.5 (95% CI 8.3 to 41.0) . The nasopharyngeal carriage rate of Hib was zero in 621 healthy Chinese children and 1.3% (95% CI 0.04 to 2.63%) in 300 healthy Vietnamese refugees 2 months to 5 years old in Hong Kong . The corresponding carriage rate of nontypable H . influenzae was 5.8% (95% CI 1.4 to 7.6%) in Chinese and 65.4% (95% CI 58.9 to 69.8) in Vietnamese . In a larger study of 1812 healthy Chinese children between 6 months and 5 years of age investigated by throat swabs, again no Hib was isolated but 141 children (7.8%) were found to be carriers of nontype b H . influenzae . In a study of 596 healthy Chinese children and adults, 25% had the protective level of anti-Hib antibody of >0.15 microg/ml by 1 year and 90% had reached >0.15 microg/ml by 6 years of age . There was some evidence that these "natural" antibodies against Hib in Hong Kong Chinese were cross-reacting antibodies against antigens on other encapsulated bacteria.

Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S159 - 65
Study on Haemophilus influenzae type b diseases in China: the past, present and future; Yang Y et al.; Meningitis caused by Haemophilus influenzae type b (Hib) is a common and serious disease for which there now are WHO-certified vaccines that are recommended for universal infant immunization in North America and European countries . If these vaccines are to be recommended in Asia, it is necessary to know the incidence, age distribution and clinical outcome of Hib meningitis and other systemic infections in this region . Data on Hib disease in China are scanty . Hib meningitis was common during the 1950s in China, accounting for up to 16% of all of pyogenic meningitis (up to 38% of cases were caused by unknown pathogens), despite severe epidemics of meningococcal meningitis during that period . Since 1989 we have conducted hospital- and community-based etiologic and epidemiologic studies of bacterial meningitis . Hib accounts for 30 to 50% of bacterial meningitis in China . The incidence of Hib meningitis in Hefei City was 10.4 per 100000 children <5 years, a result relatively lower than in the West but higher than the rate of 2.7 found in a retrospective study in Hong Kong . Pneumonia is the primary cause of death for Chinese children . From 1991 to 1993 the average mortality of children<5 years because of pneumonia was 1563.2 per 100000 . To achieve the goal of reducing the death rate of children by one-third by the year 2000, greater efforts should be made to reduce the mortality of children with pneumonia . Our preliminary study showed that about one-fourth to one-third of cases of pneumonia in Chinese children might be caused by Hib . Therefore Hib vaccination for infants and children in China might be an effective and valuable procedure to achieve the goal.

Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S152 - 9
An assessment of the value of Haemophilus influenzae type b conjugate vaccine in Asia; Miller MA; Haemophilus influenzae type b (Hib) is a leading cause of bacterial meningitis and pneumonia . Although invasive Hib disease has been reduced substantially wherever Hib conjugate vaccines have been introduced into routine childhood immunization schedules, these vaccines are more costly compared with the vaccines routinely used in the Expanded Program for Immunization . Consequently a model was constructed to compare the expected burden of Hib disease with and without a national vaccine program for various Asian countries . Cost of the vaccine program, expected benefits of reduced deaths and savings from prevented disease treatment were assessed for each country based on the model assumptions . Model outcomes were expressed as a net cost, cost per death prevented and cost per disability-adjusted life year for each country and economic stratum . With the assumption of a disease burden of meningitis and pneumonia comparable with that observed in other regions, the model predicts that 668000 cases of Hib pneumonia and 136000 cases of Hib meningitis would occur annually in this cohort resulting in 156000 deaths . Based on current vaccination coverage rates for the individual countries, the model predicted that approximately 136000 (87%) Hib deaths could be prevented annually with incorporation of Hib vaccine into the Expanded Program for Immunization . For each of the countries considered, routine vaccination with Hib would cost between 0.1 and 3.0% of per capita gross national product per child <5 years of age . Although Hib vaccine would be considered a cost-effective public health intervention, it may be cost-prohibitive to implement in the lowest income countries without initial donor assistance.

Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S148 - 51
Need for Haemophilus influenzae type b vaccination in Asia as evidenced by epidemiology of bacterial meningitis; Peltola H; OBJECTIVE: To evaluate the role of Haemophilus influenzae type b (Hib) infections in Asia by scrutinizing data on Hib meningitis . DESIGN: A comprehensive literature search was performed in English and other languages . Special attention was paid to the age group of 0 to 4 years, in which the great majority of Hib meningitis occurs . RESULTS: Twenty studies from as many countries indicated Hib to be a major pathogen in childhood meningitis . In series comprising nearly 2000 patients, Hib was responsible for at least 50% of cases in one-third of series and for at least 25% in three-fourths of series investigated and was the leading pathogen overall . The countries in South and Southeast Asia differed from the Middle East and East Asia in having a greater incidence of meningitis during the first 6 months of life; the proportions were 50 to 60% vs . 10 to 30%, respectively (P < 0.001) . CONCLUSIONS: Despite lacking data from many areas, belief in a paucity of Hib disease in Asia is not supported by the existing data; and because meningitis represents only 50 to 75% of all classical Hib manifestations and some cases occur after the age of 4 years, vaccination is warranted . The cumulative age curves suggest that conjugates with good immunogenic potential should be used, especially in South and Southeast Asia.

Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S139 - 48
The introduction of routine Haemophilus influenzae type b conjugate vaccine in Chile: a framework for evaluating new vaccines in newly industrializing countries; Lagos R et al.; OBJECTIVE: To determine the burden of Haemophilus influenzae type b (Hib) disease, the safety and immunogenicity of Hib conjugate vaccine, the practicality of combining Hib conjugate and diphtheria-tetanus-pertussis vaccines and the effectiveness of routine vaccination . STUDY DESIGNS: A series of studies were carried out involving infants and children in Santiago, Chile . The study designs included retrospective surveillance, cost-benefit analysis, randomized placebo-controlled trials of safety and immunogenicity and a Phase IV postlicensure evaluation of vaccine effectiveness . RESULTS: The studies included in this stepwise process showed that Hib invasive disease was a significant public health problem with a substantial economic burden; that combining Hib conjugate and diphtheria-tetanus-pertussis vaccines was practical, safe and elicited a strong immunologic response; and that the combined formulation afforded a high level of protection against invasive Hib disease (90% effectiveness) . CONCLUSIONS: In July, 1996, Chile became only the third newly industrializing country to introduce routine Hib conjugate vaccination . New vaccines, such as Hib conjugates, will be more expensive than existing ones . The stepwise process used in Chile may serve as an example for the evaluation of new vaccines in nonindustrialized countries.

Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S136 - 9
The introduction of Haemophilus influenzae type b immunization into the United Kingdom: practical steps to assure success; Salisbury DM; Haemophilus influenzae type b (Hib) vaccine was introduced into the routine childhood immunization program in the UK in October, 1992 . The implementation was coordinated on a national basis, taking account of market research of the information needs of both the public and health professionals . Vaccine distribution arrangements were linked to the scheduling of children for immunization, which was implemented through a national computerized system of calling children for immunization . All children commencing immunization were called for three doses of Hib vaccine . Children < 1 year of age were called back for three doses of vaccine; children >1 but <4 years were called for one dose . No boosters were given . National coverage from the outset of the campaign exceeded 90%; it is now 95% and the incidence of invasive Hib infection has declined by >95% . Some of the lessons learned from the UK introduction may be of relevance to other countries presently considering the implementation of Hib immunization into their routine immunization programs.

Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S132 - 6
Epidemiology of Haemophilus influenzae type b disease and impact of Haemophilus influenzae type b conjugate vaccines in the United States and Canada; Wenger JD; Haemophilus influenzae type b (Hib) was the major cause of invasive bacterial disease in the United States and Canada before the introduction of Hib conjugate vaccines . Between 10000 and 20000 cases of Hib meningitis and other serious diseases occurred each year, leading to death in at least 3% of all patients and long term neurologic problems in up to 25% of survivors of meningitis . Introduction of Hib conjugate vaccines in Canada and the United States, first in children 18 months and older and later as a routine infant immunization, dramatically decreased the incidence of disease . By 1995 Hib disease levels had declined by more than 95% below preimmunization levels . The remarkably rapid reduction in disease incidence was partly because of the ability of the vaccine to reduce nasopharyngeal carriage of the organism, leading, when given widely, to reduced rates of exposure and infection even in those not immunized . Complete elimination of Hib disease in North America, however, will require achievement of relatively high coverage rates, especially in hard to reach populations where much of the remaining disease is occurring.

Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S126 - 32
Haemophilus influenzae type b disease and vaccination in Europe: lessons learned; Peltola H; OBJECTIVE: To scrutinize the experiences of those European countries that have played a central role in understanding the behavior of and vaccination for Haemophilus influenzae type b (Hib) diseases, to enlighten weaknesses and to explore whether lessons learned would benefit other countries in combating Hib . DESIGN: Epidemiologic and clinical data on Hib infections and vaccinations were analyzed, including all disease manifestations and all age groups . To improve reliability, sources that used active case finding were especially searched for . RESULTS: In the prevaccination era meningitis represented 40 to 70% of all classical Hib diseases . Epiglottitis was the second most common presentation, except in southern Europe (data not available from former socialist countries) . The overall incidence of meningitis and of all Hib disease combined for children ages 0 to 4 years was 23 and 41 per 100000, suggesting 9900 and 17800 cases per year, respectively . Including all age groups and entities, >20000 Hib cases occurred annually . Vaccination, accomplished with two or three primary doses and a late booster, has almost eliminated Hib disease in >10 countries, and >10000 cases per year are prevented . An age analysis of Hib meningitis suggests that strong early immunogenicity is not as imperative in Europe as in some other regions . The incidence of non-type b H . influenzae infections has not increased . CONCLUSIONS: With Hib epidemiology comparable with that in Europe, good protection is achieved by various conjugate vaccines also with two primary doses only . However, active research on the whole Hib issue should be a priority, especially in southern and eastern European countries.

Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S123 - 5
The Gambian Haemophilus influenzae type b vaccine trial: what does it tell us about the burden of Haemophilus influenzae type b disease?
Mulholland EK, Adegbola RA.
The true burden of disease caused by Haemophilus influenzae type b (Hib) remains a mystery in many parts of the developing world . The most frequent manifestations of Hib disease are pneumonia and meningitis . In developing countries where it has been studied, Hib has proved to be a major cause of infant meningitis, generally occurring with greater frequency, in younger infants and with a worse outcome than in industrialized countries in the prevaccine era . The burden of Hib pneumonia is more difficult to define . Studies from developing countries of pneumonia etiology suggested that Hib was responsible for 5 to 10 of episodes of severe pneumonia . A Gambian study found Hib to be responsible for 7% of cases . However, a recently published trial of a Hib conjugate vaccine in Gambian infants showed that the vaccine prevented 21% of episodes of severe pneumonia in vaccine recipients, suggesting that this is the true contribution of Hib to the burden of severe pneumonia . The same trial demonstrated a mild herd effect, so this figure may be an underestimate . The biases that lead to the underestimation of the contribution of Hib to the pneumonia burden also apply to estimates of the proportion of severe pneumonia caused by Streptococcus pneumoniae . Vaccine trials may reveal the true burden of that pathogen also.

Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S117 - 22
Haemophilus influenzae type b conjugate vaccines: a review of efficacy data; Heath PT; BACKGROUND: The development of a vaccine against Haemophilus influenzae type b (Hib) was stimulated by its recognition as a major pathogen of early childhood . The first vaccine to be developed was composed of the capsular polysaccharide of the organism, polyribosylribitol phosphate (PRP), and although effective in older children, it failed to protect those <2 years of age, the group with the highest burden of disease . The conjugation of PRP to protein led to a group of vaccines with enhanced immunogenicity and the ability to induce immunologic memory and thus the potential to protect in infancy . OBJECTIVES: To review the trials of Hib conjugate vaccines in which protective efficacy in infants has been assessed and the experience in countries in which Hib conjugate vaccines have been introduced into the routine infant immunization schedule . DISCUSSION: Each of the Hib conjugate vaccines {PRP-diphtheria toxoid conjugate (PRP-D), PRP conjugated to outer membrane protein of Neisseria meningitidis group B (PRP-OMP), PRP oligosaccharides conjugated to mutant diphtheria toxin CRM197, (HbOC) and PRP conjugated to tetanus toxoid (PRP-T)} has been subjected to prospective clinical trials and all have demonstrated high protective efficacy with one exception: that of the least immunogenic vaccine, PRP-D, when used in a Native American population with a high level of natural disease . The trials have used different populations and different schedules, which limits conclusions about relative efficacies . However, it seems likely that all the vaccines are capable of high efficacy in populations with low levels and late age of Hib disease . Three vaccines (PRP-D, PRP-OMP, PRP-T) have been tested in populations with high rates of disease and only PRP-D has been found lacking . As predicted by immunogenicity data, PRP-OMP affords efficacy after one dose, and PRP-T is efficacious with an accelerated schedule . Of more practical significance the effectiveness of these vaccines when introduced into populations has been uniformly impressive . CONCLUSIONS: Particularly where vaccine coverage is high, it is now likely that Hib disease can be eliminated using Hib conjugate vaccines in infancy.

Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S113 - 6
Haemophilus influenzae type b vaccines: history, choice and comparisons; Decker MD et al.; The conjugate Haemophilus influenzae type b (Hib) vaccines are safe and far more immunogenic among infants and young children than is the unconjugated H . influenzae type b polysaccharide . The vaccines differ in their immunogenicity when used for primary immunization of infants, and these differences appear to be predictive of efficacy, such that some vaccines might be more suitable than others in certain populations.

Kansenshogaku Zasshi, 1998 Aug, 72(8), 781 - 7
{Risk factors for clinical prognosis in bacterial meningitis beyond the neonatal period}; Nagai K et al.; A retrospective clinical study of 64 cases with bacterial meningitis beyond the neonatal period in the department of pediatrics of St . Mary's Hospital (1985-1995) was conducted . Haemophilus influenzae (H . influenzae) (28 cases, 43.8%) and Streptococcus pneumoniae (S . pneumoniae) (23 cases, 35.9%) were common pathogens . The prognosis was classified into three groups; normal (42 cases, 65.6%), neurological sequelae (17 cases, 26.6%) and death (5 cases, 7.8%) . We analyzed the risk factors associated with their outcome . The body temperature at admission, platelet count, CSF examination (WBC, glucose, GOT, GPT) were prognostic factors . The prognosis of bacterial meningitis caused by S . pneumoniae was worse than those due to H . influenzae (p = 0.0347).

An Med Interna, 1998 Aug, 15(8), 439 - 42
{Which are the vaccines that human immunodeficiency virus infected patients must receive?}; Valencia Ortega ME et al.; Patients with aids are at increased risk of opportunistic and non opportunistic infections . It is now known that the incidence can be reduced by prophylactic measures and/or the use of vaccines . HIV infection produces an elevated frequency of severe pneumococcal disease with a rate of bacteriemia caused by Streptococcus pneumoniae 150-300 fold greater than rates reported in non-HIV infected people . For this reason, pneumococcal vaccine should be administered as early as possible in the course of the infection . Besides, the antibody response may be significantly higher for asymptomatic persons . Acute hepatitis caused by hepatitis B virus is milder than in non HIV infected patients but chronic disease is more frequent . The prognosis is worse and there is higher risk for infecting another persons . Hepatitis B vaccine is indicated for all the patients with HIV and negative serology for hepatitis B virus . Influenza vaccine is of limited effectiveness due to the high variability of the virus . Besides, influenza incidence is low among approximately young adults, HIV related immunodeficiency increased influenza risk only minimally, the vaccine is administered yearly and HIV-replication can increase in temporal association with vaccination . For all these reasons, fewer hospitalizations and deaths are prevented making it a far less cost-effective prevention strategy than pneumococcal vaccination . The risk of Haemophilus influenzae infections is elevated, but the vaccine is not routinely recommended because the more frequent serotype in HIV infected patients is b . For these subjects, passive immunization with immunoglobulin may also be necessary to provide protection . In conclusion, pneumococcal and hepatitis B vaccination is a reasonable prevention strategy for HIV infected patients at all stages of immunodeficiency . Influenza and H . influenzae vaccination are not recommended and alternative prevention strategies may be done.

J Immunol, 1998 Oct 15, 161(8), 4177 - 82
Haemophilus influenzae type b polysaccharides-protein conjugate vaccine elicits a more diverse antibody repertoire in infants than in adults; Adderson EE et al.; Conjugation of bacterial polysaccharides (PS) to protein carriers confers the ability to elicit protective serum Ab in infants, who respond poorly to plain PS . The serum Ab of young children immunized with Haemophilus influenzae type b (Hib) PS conjugate vaccine varies with age and Ag formulation . To understand these age-related changes in human anti-Hib PS immune responses we determined the variable region gene sequences encoding anti-Hib PS mAbs of infants immunized with Hib oligosaccharide-diphtheria toxin vaccine . The anti-Hib PS repertoire of children differs from that of adults . A smaller proportion of mAbs from children have high affinity for Hib PS, and the overall variable region gene repertoire of infants is more diverse than that in adults . Variable region genes encoding high affinity mAbs of infants are similar to the restricted repertoire described in adults . Low affinity anti-Hib PS mAbs of infants are encoded by a heterogeneous group of genes that are uncommonly observed in the adult repertoire . Abs with high affinity for Hib PS from infants, like most mAbs from adults, react only with Hib PS and the structurally similar PS of Escherichia coli K100, whereas low affinity mAbs of infants are polyreactive . The low affinity anti-Hib PS mAbs of infants immunized with Hib oligosaccharide-diphtheria toxin vaccine vaccine are not reflected in serum Ab . However, the differences between the variable region gene repertoires of adults and infants may account for the distinct immunologic characteristics of the anti-Hib PS responses in young children immunized with other vaccine formulations.

Pediatr Infect Dis J, 1998 Sep, 17(9), 782 - 6
The epidemiology of Haemophilus influenzae type b carriage among infants and young children in Santo Domingo, Dominican Republic; Gomez E et al.; BACKGROUND: Whether herd immunity will occur with widespread Haemophilus influenzae type b (Hib) vaccination in developing countries is dependent on whether the vaccines are capable of reducing carriage in these settings . However, few population-based studies of Hib carriage in developing countries exist . METHODS: To study Hib carriage in the Dominican Republic, we collected nasopharyngeal swab specimens from a population-based sample of 983 children 0 to 47 months old in a periurban area of Santo Domingo . RESULTS: Nasopharyngeal swabs of 76 (7.7%) children were positive for Hib . Hib carriage varied by age group with a low of 1.5% among 0 to 5 month olds, a peak of 12.5% in 6 to 11 month olds and prevalence rates of 6.0, 7.9 and 9.8% among 1-, 2- and 3-year-olds, respectively . Hib carriage was 51% lower among currently breast-fed 6 to 11 month olds than among those not currently breast-fed (18.2% vs . 9.0%; P=0.08) . CONCLUSIONS: Infants and young children in Santo Domingo have high rates of Hib carriage, characterized by an early peak in carriage that corresponds with the peak of risk for Hib meningitis . The ability of Hib vaccines to diminish carriage to levels that will effectively reduce transmission and lead to herd immunity in this setting needs to be determined.

J Theor Biol, 1998 Oct 7, 194(3), 341 - 81
The humoral immune response to Haemophilus influenzae type b: a mathematical model based on T-zone and germinal center B-cell dynamics; Rundell A et al.; Through careful mapping of the physiology of the T-zone and GC B-blast dynamics to a mathematical representation of the cell processes including proliferation, migration, differentiation, and cell death, a mathematical model is constructed to capture the dominant nominal primary, late follicular, and secondary humoral response to Haemophilus influenzae Type b . This model explicitly incorporates the dynamics of memory B-cells, T-zone and GC B-dynamics, IgM and IgG antibodies, avidity maturation, and IC presentation by FDCs into a coherent framework . This paper describes the relevant immunology, the pertinent physiological assumptions, the developed model, and the parameter identification procedure . The model parameters were found using a parameter identification procedure that capitalizes on the timing and interactions of certain dominant physiological attributes . Simulation results and validation tests indicate that the model reflects not only a nominal primary and secondary humoral immune response but also the tertiary and T-independent responses . The model shows robustness to variations in infection dosage, bacterial growth rate (virulence of the strain), and onset-timing of the secondary response . The utility of this model in studying the humoral immune response is demonstrated through suggested physiological assumptions, mechanisms, and rates to be eventually clinically evaluated as well as insights into vaccination design . The model and parameter identification techniques are easily adapted to other diseases which primarily evoke a humoral immune response .

Arthritis Rheum, 1998 Oct, 41(10), 1828 - 34
Antigen-specific antibody responses in lupus patients following immunization; Battafarano DF et al.; OBJECTIVE: To determine the safety and efficacy of 3 clinically relevant vaccines in patients with systemic lupus erythematosus (SLE) . METHODS: We studied 73 consecutive SLE patients immunized with pneumococcal, tetanus toxoid (TT), and Haemophilus influenzae type B (HIB) vaccines . Patients were evaluated preimmunization and 12 weeks postimmunization for disease activity and immunization side effects . RESULTS: Eighty-four percent of the SLE patients developed a 4-fold titer increase in response to at least 1 vaccine, with 51% developing a 2-fold titer increase with all 3 vaccines . The majority of SLE patients developed protective levels of antibody to TT (90%) and HIB (88%) . Although protective antibody levels could not be determined for pneumococcus, almost half of the patients (47%) developed a 4-fold antibody response . There was a trend toward a lower antibody response in patients with active disease treated with immunosuppressive therapy . Overall lupus disease activity was unaffected by immunization . CONCLUSION: Immunization is safe in SLE patients, with the overwhelming majority developing protective antibody levels . Therefore, SLE patients should receive immunizations according to the recommendations of the Centers for Disease Control and Prevention and the Immunization Practices Advisory Committee.

Antibiot Khimioter, 1998, 43(8), 16 - 22
{Characteristics of fauces microflora in children treated in intensive care units}; Beloborodova NV et al.; Characteristic features of fauces aerobic microflora in children treated in intensive care units (ICU) were analysed . For comparison fauces microflora in children outpatients and in children patients from general surgical units was investigated . A retrospective analysis of all the smears without exception for 2 years (a total of 2120) revealed a direct dependence of the changes in the fauces microflora composition on the patient condition and the antibiotic load . It was shown that the fauces indigenic microflora in ICU patients was more often replaced by enterococci, gramnegative enteric bacteria and nonfermenting bacteria which are not usual under the normal conditions . The flora in such cases was represented by monoculture . Thus, microorganisms natural for the fauces i.e . Haemophilus influenzae and Neisseria spp . were not practically detected in the fauces of the ICU patients (0.5 and 0.4 per cent, respectively) . Grampositive cocci in the children of the surgical units and in the outpatients included alpha-hemolytic streptococci in association with beta-hemolytic or nonhemolytic streptococci . No such bacteria were isolated from the ICU newborns . The associations of gramnegative organisms from the ICU patients included 40 variants . Seventy-eight association variants of Pseudomonas aeruginosa were mainly represented by the combinations with Serratia spp . and Klebsiella spp . as well as with coagulase negative staphylococci or enterococci, especially in the ICU newborns . The results of the study demonstrated that the target-aimed antibiotic therapy providing eradication of P.aeruginosa in the ICU patients was not always justified because of possible superinfection practically due to any organism from the association . Massive antibiotic therapy with pressing on gramnegative flora in the ICU patients induced selective contamination of the mucosa by polyresistant enterococci thus increasing their potential role in the development of hospital infections.

Tokai J Exp Clin Med, 1997 Oct, 22(4), 167 - 74
IgA nephropathy in mice following repeated administration of conjugated Haemophilus influenzae type B vaccine (PRP-T); Kavukcu S et al.; OBJECTIVE: In this study, the risk of IgA nephropathy in Swiss albino mice following the subcutaneous administration of conjugated Haemophilus influenzae type b vaccine (PRP-T), containing capsular polysaccharide of the organism (PRP) conjugated to tetanus protein (T), was evaluated . METHODS: Three treatment and corresponding control groups, each containing mice, were constituted and given 2, 4, 6 injections of 1/4 HD of PRP-T or placebo, respectively, at 2-week intervals . All mice in each treatment group were sacrificed two weeks from the last injection to examine sequential glomerular changes . RESULTS: The niceoscpic examination of renal tissues revealed mesangial proliferation (6/7; 85%) in the first group given 2 doses of vaccine; mesangial proliferation (5/7; 72%) and increase in matrix (7/7; 100%) in the second group given 4 doses; and mesangial proliferation (7/7; 100%), increase in matrix (7/7; 100%), IgA (7/7; 100%) and C3 (3/7; 42%) deposition within mesangium in the third group given 6 doses . No histopathological changes were detected in the renal tissues of any control mouse . When the experimental groups were compared statistically with their respective controls at the light microscopic level, mesangial proliferation in the first group (p: 0.0047), mesangial proliferation (p: 0.021) and increase in matrix (p: 0.001) in the second group, mesengial proliferation (p: 0.001) and increase in matrix (p: 0.001) in the third group were determined to be significantly different . When study and control groups were compared by immunofluorescence microscopy, only the third group revealed a statistically significant difference with respect to IgA deposition (p: 0.001) . C3 deposition was also demonstrated in this group, but it was not significantly different (p: 0.192) . However, in no instance was a control mouse found to have any form of immune deposition . CONCLUSION: We concluded that conjugated Haemophilus influenzae type b vaccine, given at two-week intervals to a total of six doses, caused secondary IgA nephropathy in mice.

Clin Rheumatol, 1998, 17(4), 340 - 2
Septic arthritis caused by Haemophilus influenzae associated with endocarditis; Lesage V et al.; Septic arthritis with Haemophilus influenzae is infrequent in adults and often associated with an extra-articular septic focus . We report the case of a septic arthritis caused by H . influenzae in an elderly (89-year-old) female patient in whom an transoesophageal echocardiogram showed an aortic valve endocarditis.

Microb Comp Genomics, 1998, 3(3), 171 - 5
Assignment of folds for proteins of unknown function in three microbial genomes; Dubchak I et al.; Analysis of DNA sequences of several microbial genomes has revealed that a large fraction of predicted coding regions has no known protein function . Information about the three-dimensional folds of these proteins may provide insight into their possible functions . To predict the folds for protein sequences with little or no homology to proteins of known function, we used computational neural networks trained on the database of proteins with known three-dimensional structures . Global descriptions of protein sequences based on physical and structural properties of the constituent amino acids were used as inputs for neural networks . Of the 131, 498, and 868 protein sequences of unknown function from Mycoplasma genitalium, Haemophilus influenzae, and Methanococcus jannaschii (Fleischmann et al . 1995), we have made high-confidence fold assignments for 4, 10, and 19 sequences, respectively.

J Clin Microbiol, 1998 Nov, 36(11), 3417 - 9
Correlation between presence of viable bacteria and presence of endotoxin in middle-ear effusions; Dingman JR et al.; The presence of endotoxin (detected by the Limulus amebocyte lysate assay) was compared to the presence of viable Haemophilus influenzae and Moraxella catarrhalis (detected by PCR) in 106 middle-ear effusions from pediatric patients with chronic otitis media . Endotoxin was found in 81 of the 106 specimens . Of these 81 specimens, 66 (81.5%) also tested positive for one or both of the gram-negative bacteria H . influenzae and M . catarrhalis . The data suggest that viable gram-negative bacteria, detectable by PCR but often undetectable by culture, may be the source of endotoxin in middle-ear effusions.

Proc Natl Acad Sci U S A, 1998 Oct 13, 95(21), 12641 - 6
Human milk lactoferrin inactivates two putative colonization factors expressed by Haemophilus influenzae; Qiu J et al.; Haemophilus influenzae is a major cause of otitis media and other respiratory tract disease in children . The pathogenesis of disease begins with colonization of the upper respiratory mucosa, a process that involves evasion of local immune mechanisms and adherence to epithelial cells . Several studies have demonstrated that human milk is protective against H . influenzae colonization and disease . In the present study, we examined the effect of human milk on the H . influenzae IgA1 protease and Hap adhesin, two autotransported proteins that are presumed to facilitate colonization . Our results demonstrated that human milk lactoferrin efficiently extracted the IgA1 protease preprotein from the bacterial outer membrane . In addition, lactoferrin specifically degraded the Hap adhesin and abolished Hap-mediated adherence . Extraction of IgA1 protease and degradation of Hap were localized to the N-lobe of the bilobed lactoferrin molecule and were inhibited by serine protease inhibitors, suggesting that the lactoferrin N-lobe may contain serine protease activity . Additional experiments revealed no effect of lactoferrin on the H . influenzae P2, P5, and P6 outer-membrane proteins, which are distinguished from IgA1 protease and Hap by the lack of an N-terminal passenger domain or an extracellular linker region . These results suggest that human milk lactoferrin may attenuate the pathogenic potential of H . influenzae by selectively inactivating IgA1 protease and Hap, thereby interfering with colonization . Future studies should examine the therapeutic potential of lactoferrin, perhaps as a supplement in infant formulas.

Proc Natl Acad Sci U S A, 1998 Oct 13, 95(21), 12381 - 5
Natural genetic exchange between Haemophilus and Neisseria: intergeneric transfer of chromosomal genes between major human pathogens; Kroll JS et al.; Members of the bacterial families Haemophilus and Neisseria, important human pathogens that commonly colonize the nasopharynx, are naturally competent for DNA uptake from their environment . In each genus this process is discriminant in favor of its own and against foreign DNA through sequence specificity of DNA receptors . The Haemophilus DNA uptake apparatus binds a 29-bp oligonucleotide domain containing a highly conserved 9-bp core sequence, whereas the neisserial apparatus binds a 10-bp motif . Each motif ("uptake sequence", US) is highly over-represented in the chromosome of the corresponding genus, particularly concentrated with core sequences in inverted pairs forming gene terminators . Two Haemophilus core USs were unexpectedly found forming the terminator of sodC in Neisseria meningitidis (meningococcus), and sequence analysis strongly suggests that this virulence gene, located next to IS1106, arose through horizontal transfer from Haemophilus . By using USs as search strings in a computer-based analysis of genome sequence, it was established that while USs of the "wrong" genus do not occur commonly in Neisseria or Haemophilus, where they do they are highly likely to flag domains of chromosomal DNA that have been transferred from Haemophilus . Three independent domains of Haemophilus-like DNA were found in the meningococcal chromosome, associated respectively with the virulence gene sodC, the bio gene cluster, and an unidentified orf . This report identifies intergenerically transferred DNA and its source in bacteria, and further identifies transformation with heterologous chromosomal DNA as a way of establishing potentially important chromosomal mosaicism in these pathogenic bacteria.

Rev Cubana Med Trop, 1996, 48(2), 130 - 2
{Urethritis caused by serotype B Haemophilus influenzae . Report of a case}; Llanes Caballero R et al.; A case of a patient with schistosomiasis haematobium history, from Mozambique, is presented . This patient was admitted in the Institute of Tropical Medicine for having urination troubles and purulent urethral secretion . Serotype B Haemophilus influenzae, biotype i.v . of the urethra, was isolated . The strain was sensitive to ampicillin, chloramphenicol, ceftraxione, and norfloxacin, and resistant to tetracycline and erythromycin . The patient got better after receiving treatment with norfloxacin . A comment is made on the role of this microorganism as a sexual transmission pathogen.

J Med Chem, 1998 Oct 8, 41(21), 4080 - 100
Synthesis and antibacterial activity of ketolides (6-O-methyl-3-oxoerythromycin derivatives): a new class of antibacterials highly potent against macrolide-resistant and -susceptible respiratory pathogens; Agouridas C et al.; In the search for new antibiotics active against macrolide-resistant pneumococci and Haemophilus influenzae, we synthesized a new class of 3-oxo-6-O-methylerythromycin derivatives, so-called "ketolides" . A keto function was introduced in position 3 after removal of L-cladinose, a sugar which has long been thought essential . Further modifications of the macrolactone backbone allowed us to obtain three different series of 9-oxime, 11,12-carbamate, and 11, 12-hydrazonocarbamate ketolides . These compounds were found to be very active against penicillin/erythromycin-resistant pneumococci and noninducers of MLSB resistance . The 11,12-substituted ketolide 61 (HMR 3004) demonstrated a potent activity against multiresistant pneumococci associated with a well-balanced activity against all bacteria involved in respiratory infections including H . influenzae, Mycoplasma catarrhalis, group A streptococci, and atypical bacteria . In addition HMR 3004 displayed high therapeutic activity in animals infected by all major strains, irrespective of their resistance phenotype.

Mol Microbiol, 1998 Aug, 29(4), 1065 - 76
The Escherichia coli relBE genes belong to a new toxin-antitoxin gene family; Gotfredsen M et al.; Toxin-antitoxin systems are defined as a group of plasmid- and chromosome-encoded loci that specify a cell toxin and a protein antitoxin . Plasmid-encoded toxin-antitoxin systems stabilize their replicons by killing plasmid-free cells . Here, we show that the relBE genes of Escherichia coli K-12 have all the basic features previously connected with toxin-antitoxin systems: (i) relE encodes a cytotoxin lethal or inhibitory to host cells; (ii) relB encodes an antitoxin that prevents the lethal action of the relE-encoded toxin; (iii) the relBE genes stabilize a mini-R1 test plasmid; and (iv) the RelB antitoxin autoregulates the relBEF operon at the level of transcription . Using database searching, we found relBE homologues on the chromosomes of E . coli K-12, Haemophilus influenzae and Vibrio cholerae . A fifth relBE homologue was identified on the enterotoxin encoding E . coli plasmid P307 . Indirect evidence suggests that the toxicity of RelE may be related to the inhibition of protein synthesis . Based on these observations, we propose a model that explains the delayed relaxed phenotype associated with mutations in relB.

Cytogenet Cell Genet, 1998, 82(1-2), 101 - 4
Genomic structure of a novel human gene (XYLB) on chromosome 3p22-->p21.3 encoding a xylulokinase-like protein; Tamari M et al.; We isolated a novel human cDNA of 1963 nucleotides that included an open reading frame encoding a protein of 528 amino acids . Homology analysis indicated that the predicted gene product, XYLB, bore 22% identity to the xylulokinase of Haemophilus influenzae that plays an important role in energy metabolism . The gene consists of 18 exons and spans about 28 kb of genomic DNA on chromosome 3p21.3.

Int J STD AIDS, 1998 Sep, 9(9), 531 - 6
Clinical and in situ cellular responses to Haemophilus ducreyi in the presence or absence of HIV infection; King R et al.; We aimed to determine if the clinical and histological features of chancroid are altered by HIV infection . Male patients presenting to the Nairobi special treatment clinic with a clinical diagnosis of chancroid were eligible for the study . A detailed history, physical examination, swabs for Haemophilus ducreyi culture and blood for HIV serology, syphilis serology and CD4 counts were obtained from all patients . Punch biopsies from an ulcer were obtained from 10 patients and either fixed in 10% formalin or snap frozen in Optimum Cutting Temperature (OCT) medium compound at -70 degrees C . Patients were treated with erythromycin and followed for 3 weeks . Chi-square and Student's t-test were used to determine if the clinical and laboratory features of chancroid differed between HIV-seropositive and seronegative individuals . Cox regression survival analysis was used to determine if HIV infection altered cure rates of chancroid at 21 days . Immunohistochemical staining was performed using lymphocytic and macrophage markers and tissue sections were analysed by 2 pathologists in a blinded manner . Between February and November 1994, 109 HIV-seropositive and 211 HIV-seronegative individuals were enrolled in the study . HIV patients had ulcers of longer duration than HIV-seronegative patients (P=0.03) . Although cure rates were similar at 3 weeks, HIV patients had lower cure rates at 1 week (23% v 54%, P=0.002) . A dense interstitial and perivascular inflammatory infiltrate extending from the reticular to deep dermis was present in all biopsies . This consisted of equal amounts of CD4 and CD8 T-lymphocytes as well as macrophages . The histological and immunohistochemical picture was identical for HIV-positive and negative patients . HIV infection slows the healing rates of chancroid ulcers despite appropriate antibiotic therapy . This clinical difference cannot be attributed to an altered histopathological response to HIV infection . Additional studies are needed to elucidate the mechanisms responsible for this findingPIP: Chancroid is caused by infection with Hemophilus ducreyi, and is associated with an increased risk for the sexual transmission of HIV-1 . The authors assessed whether the clinical and histological features of chancroid are changed by HIV infection, using 320 male patients who presented during February-November 1994 to the City of Nairobi Special Treatment Clinic with a clinical diagnosis of chancroid . 109 subjects were HIV seropositive and 211 were HIV seronegative . A detailed history, physical examination, swabs for Hemophilus ducreyi culture and blood for HIV serology, syphilis serology, and CD4 counts were obtained from all patients . Punch biopsies from an ulcer were obtained from 10 patients and either fixed in 10% formalin or snap frozen in Optimum Cutting Temperature (OCT) medium compound at -70 degrees Celsius . Patients were treated with erythromycin and followed for 3 weeks . HIV patients had ulcers of longer duration than did HIV-seronegative patients . Although cure rates were similar at 3 weeks, HIV patients had lower cure rates at 1 week (23% vs . 54%) . A dense interstitial and perivascular inflammatory infiltrate extending from the reticular to deep dermis was present in all biopsies . The infiltrate consisted of equal amounts of CD4 and CD8 T-lymphocytes as well as macrophages . The histological and immunohistochemical picture was identical for HIV-positive and HIV-negative patients . Study findings therefore indicate that HIV infection slows the healing rates of chancroid ulcers despite appropriate antibiotic therapy . The clinical difference cannot be attributed to an altered histopathological response to HIV infection .

J Chromatogr A, 1998 Aug 21, 817(1-2), 325 - 36
Development of an on-line preconcentration method for the analysis of pathogenic lipopolysaccharides using capillary electrophoresis-electrospray mass spectrometry . Application to small colony isolates; Li J et al.; The present investigation describes the use of on-line chromatographic preconcentration coupled to capillary zone electrophoresis-electrospray mass spectrometry (cPC-CZE-ES-MS) for trace level analysis of negatively charged lipopolysaccharides (LPS) obtained from pathogenic strains of Haemophilus influenzae . The analytical performance of two different types of adsorption media {i.e., C18 irregular particles and poly(styrene-divinylbenzene) membrane} for anionic analytes was first evaluated using a mixture of peptide standards to determine the overall sensitivity of this approach . These chromatographic preconcentrators provided an enhancement of sample loadings of up to 5 microliters with good linear response and low nM concentration detection limits for most peptides investigated . The application of cPC-CZE-ES-MS is further demonstrated for extracts of O-deacylated LPS obtained from H . influenzae strain Eagan . In combination with novel enzymatic releasing methods using proteinase K, this technique provides unparalleled sensitivity and enabled the identification of LPS surface antigens from as little as five bacterial colonies.

Diagn Microbiol Infect Dis, 1998 Aug, 31(4), 573 - 8
In vitro evaluation of a novel orally administered cephalosporin (Cefditoren) tested against 1249 recent clinical isolates of Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae; Jones RN et al.; Cefditoren (formerly ME-1206), a new orally administered cephalosporin, was evaluated in vitro against 1249 recently isolated strains of Streptococcus pneumoniae (500 strains), Moraxella catarrhalis (250 strains), and Haemophilus influenzae (499 strains) . Reference National Committee for Clinical Laboratory Standards methods were used and the strains were representative for the current rates of beta-lactamase production or penicillin resistance . Cefditoren had MIC50/MIC90 results for Moraxella catarrhalis and Haemophilus influenzae of 0.12/0.5 and < or = 0.008/0.015 microgram/mL, respectively . The pneumococci were consistently twofold to eightfold more susceptible to cefditoren than other oral cephalosporins or penicillins . The MIC90 for penicillin-resistant S . pneumoniae was only 2 micrograms cefditoren/mL, and the highest recorded MIC was 4 micrograms/mL . Cefditoren appears to be a very promising beta-lactam possessing the greatest potency and potential spectrum versus contemporary (1997) respiratory tract pathogens.

Arch Pediatr, 1998 May, 5(5), 557 - 60
{What uses for the acellular pertussis vaccine?}; Grimprel E et al.; The acellular pertussis vaccine offers a better tolerance as compared with the whole cell pertussis vaccine . It has also a good protective effect against whooping cough . However given as a combined pentavalent vaccine for the primary immunization of infants, it appears to introduce an immune interference leading to a diminished response to the Haemophilus type b or poliomyelitis valence according to the type of vaccine . Thus it is recommended that immunization against whooping cough in France in the coming years uses whole cell pertussis combined vaccine for the primary immunization of infants at 2, 3 and 4 months, the acellular pertussis vaccine being used for the booster injections at 18 months and 10-11 years.

Arch Pediatr, 1998 Apr, 5(4), 384 - 8
{International registry on mucoviscidosis: comparison of the French data with the European data for 1995}; Delaisi B et al.; BACKGROUND: The Epidemiologic Registry of Cystic Fibrosis (ERCF) is an international registry, sponsored by Roche Laboratories, collecting data about CF patients in Europe . The aim of the our study is to compare the French data with the European data collected during the year 1995 . RESULTS: By December 31st 1995, 8,831 patients have been enrolled in Europe, including 1,457 patients in France . French CF patients are younger (mean age = 12.6 years) than European CF patients (mean age = 14.6 years) . Genotype is better characterised in France (89 vs 75% for European patients), but only 49% of CF patients are homozygote for the DF508 deletion in France versus 77% in Denmark . Two clinical features of French CF patients are interesting: 1) presence of Staphylococcus aureus and Haemophilus influenzae (52%) is more frequent in France than in Europe (65 vs 48% and 52 vs 29%, respectively), 2) lung function tests (forced vital capacity {FVC}), forced expiratory volume per second {FEV1} are worse in France (P < 0.001) particularly in the older patients (> 18 years): 39% of these patients in France have a FEV1 < 40% of predicted value compared to only 29% in Europe . Similarly there are fewer patients in this age group in France (22 vs 31% in Europe) having a FVC > 90% of the predicted value in France . With regard to the treatment, three differences emerge: 1) dornase alfa is more used in France (55 vs only 34% in Europe); 2) use of prophylactic inhaled and oral antibiotics is less common in France than in all age groups; 3) the use of inhaled corticosteroids and bronchodilators is also less common in France despite the same incidence of asthma-like symptoms . Finally we notice that the mean age at death in 1995 is 18.2 years (+/- 2.38) in France and 20.6 years (+/- 0.85) in Europe . CONCLUSION: These results are preliminary because 1995 is the first year for ERCF in France and a low percentage of French CF patients are included for this year . Therefore they must be interpreted with caution . Nevertheless, we can hypothesise about a relationship between these results and a less aggressive treatment regimen . The impact of dornase alfa use on prognosis seems interesting to analyse in future years.

J Immunol, 1998 Oct 1, 161(7), 3776 - 80
Role of kappa II-A2 light chain CDR-3 junctional residues in human antibody binding to the Haemophilus influenzae type b polysaccharide; Lucas AH et al.; Abs using the kappaII-A2 V gene segment predominate the human Ab repertoire to the Haemophilus influenzae b (Hib) polysaccharide (PS) . All A2 anti-Hib PS Abs sequenced to date possess a 10-amino acid L chain complementarity-determining region-3 (CDR-3) having an insertional arginine (Arg) at position 95a, the V-J junction . These findings suggest an essential requirement for this conserved Arg residue in determining Hib PS-binding affinity . We examined this requirement by performing chain recombination experiments in which a series of A2 L chains, differing at position 95a, were combined individually with an Fd region known to generate a Hib PS-combining site when paired with an A2-Arg(95a)-Jkappa1 V region . Hib PS binding of the recombinant Fabs was evaluated quantitatively using a radioantigen-binding assay . Fabs having A2 L chains with either Arg or lysine in position 95a in combination with Jkappa1 gave equivalent and strongest binding to Hib PS . Fabs having A2-Jkappa1 L chains with either tyrosine, glycine, alanine, leucine, serine, or threonine in position 95a, or having an A2-Arg(95a)-Jkappa3 L chain, gave intermediate binding . Fabs having A2-Jkappa1 L chains with glutamate or aspartate at 95a or with no junctional residue showed little or no Hib PS binding . These results demonstrate the importance of L chain junctional residue, as well as Jkappa usage and CDR-3 length, in determining Hib PS-binding affinity . Contrary to expectation, an Arg junctional residue is not essential for generating either high or intermediate affinity-binding sites.

Protein Expr Purif, 1998 Oct, 14(1), 113 - 9
Design of protein purification pathways: application to the proteome of Haemophilus influenzae using heparin chromatography; Fountoulakis M et al.; The design of efficient protein purification protocols is a scientific challenge and can be facilitated by the use of master protein enrichment or purification steps . A master purification step is in principle a list including the major proteins expected to be present in the various fractions collected from a particular enrichment process . Consideration of a master step in the design of a purification pathway can reduce the time and effort usually invested in "trial and error" approaches . Moreover, master purification steps will certainly become valuable tools in the isolation of proteins today designated as hypothetical or predicted coding regions, resulting from the sequencing of the various genomes, and for which no information on their purification exists . The construction of such a master step consists of performance of the protein separation by the particular chromatographic method, analysis by two-dimensional polyacrylamide gel electrophoresis, and identification by mass spectrometry of the proteins present in each fraction . This can be efficiently accomplished now thanks to developments in two-dimensional gel technology and large-scale sample throughput mass spectrometry . Here we present an example of construction of a master protein enrichment step using the soluble protein fraction of the bacterium Haemophilus influenzae and applying Heparin chromatography .

Eur J Clin Microbiol Infect Dis, 1998 Jun, 17(6), 447 - 53
Trovafloxacin versus high-dose amoxicillin (1 g three times daily) in the treatment of community-acquired bacterial pneumonia; Tremolieres F et al.; Once-daily trovafloxacin 200 mg was compared with high-dose amoxicillin, 1 g three times daily, given for 7 to 10 days . At end of treatment (day 10), the response was clinically successful (cure + improvement) in 93% of 152 clinically evaluable trovafloxacin patients and in 89% of 160 amoxicillin patients . At study end (day 35), respective rates were 91% and 81% (95% confidence interval: 1.6, 17.6; P=0.01) . In evaluable patients with positive baseline radiographs, 93% of trovafloxacin and 88% of amoxicillin patients demonstrated radiological resolution at end of treatment . Streptococcus pneumoniae and Haemophilus influenzae eradication rates were comparable at end of treatment in both treatment groups, but at study end Streptococcus pneumoniae eradication rates were higher in trovafloxacin patients (100% vs 81%) . At study end, all four trovafloxacin patients with baseline penicillin-resistant Streptococcus pneumoniae were clinically cured with pathogen eradication, whereas two of five amoxicillin patients with baseline penicillin-resistant Streptococcus pneumoniae were clinical failures with pathogen persistence . For patients in whom no pathogen was identified, trovafloxacin was significantly more effective at end of treatment (P=0.096) and study end (P=0.013) . Treatment-related adverse events were comparable; the most common were headache, vomiting and dizziness in trovafloxacin patients, and diarrhoea . headache and abdominal pain in amoxicillin patients.

Eur J Clin Microbiol Infect Dis, 1998 Jun, 17(6), 441 - 6
Treatment of acute exacerbations of chronic bronchitis: comparison of trovafloxacin and amoxicillin in a multicentre, double-blind, double-dummy study . Trovafloxacin Bronchitis Study Group; O'Doherty B et al.; The efficacy and safety of trovafloxacin and amoxicillin were compared in a double-blind, double-dummy multicentre trial involving 412 patients (> or = 40 years of age) with acute exacerbations of chronic bronchitis (AECBs) . Patients were randomized to 5 days' oral treatment with 200 or 100 mg trovafloxacin administered once daily, or 500 mg amoxicillin given three times daily . Overall clinical efficacy at the end of therapy was similar in each treatment group, with clinical success (cure+improvement) achieved in 88% and 91% of clinically evaluable patients receiving trovafloxacin 200 mg and 100 mg, respectively, and in 89% of amoxicillin-treated patients . Corresponding rates at follow-up were 77%, 85% and 79%, respectively . Similar responses were noted at the end of treatment and end of study in the intent-to-treat patients . Although all three treatments produced similar bacteriological efficacy, there was a trend towards higher eradication rates for Haemophilus influenzae among patients (both clinically evaluable and intent-to-treat populations) treated with trovafloxacin 200 mg compared with those treated with amoxicillin . Both drugs were well tolerated, with treatment-related adverse events, of which headache and gastrointestinal disturbances were the most common, occurring in 12% and 6% of patients in the trovafloxacin 200 mg and 100 mg groups, respectively, and in 9% of amoxicillin-treated patients.

Eur J Clin Microbiol Infect Dis, 1998 Jun, 17(6), 434 - 40
Trovafloxacin versus amoxicillin/clavulanic acid in the treatment of acute exacerbations of chronic obstructive bronchitis; Leophonte P et al.; Treatments with once-daily trovafloxacin (200 or 100 mg) and amoxicillin/clavulanic acid (500/125 mg three times daily) were compared in adults with acute exacerbations of chronic obstructive bronchitis . At end of treatment, 95% (113/119) of clinically evaluable patients receiving trovafloxacin 200 mg, 98% (113/115) of patients treated with trovafloxacin 100 mg and 97% (113/117) of patients receiving amoxicillin/clavulanic acid were cured or improved . At study end, 91%, 87% and 88%, respectively, were cured or improved . At end of treatment, trovafloxacin 200 mg eradicated Haemophilus influenzae in 97% of patients, Streptococcus pneumoniae in 90% and Chlamydia pneumoniae in 100% . The respective eradication rates for trovafloxacin 100 mg were 84%, 100% and 100%; those for amoxicillin/clavulanic acid were 92%, 100% and 100% . At study end, trovafloxacin 200 mg totally eradicated all three pathogens . Trovafloxacin 100 mg eradicated Haemophilus influenzae in 91% of patients, Streptococcus pneumoniae in 100% and Chlamydia pneumoniae in 80% . Respective eradication rates for amoxicillin/clavulanic acid were 78%, 100% and 80% . Only 7% (10/144) of patients receiving trovafloxacin 200 mg reported treatment-related adverse events, as did 7% (10/135) of patients given trovafloxacin 100 mg and 12% (17/140) of patients given amoxicillin/clavulanic acid.

Eur J Clin Microbiol Infect Dis, 1998 Jun, 17(6), 413 - 9
Susceptibility of European respiratory tract isolates to trovafloxacin, ciprofloxacin, clarithromycin, azithromycin and ampicillin; Pontani D et al.; As part of the Artemis project, 11500 isolates (3000 from patients with respiratory tract infections) were collected throughout six European countries between 1994 and 1996 . Twenty-seven hospitals or laboratories participated in this first phase of the study . The activities of three classes of antimicrobial agents (fluoroquinolones, beta-lactam agents, macrolides) are presented for the six most frequently isolated pathogens (Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, Pseudomonas aeruginosa, Klebsiella pneumoniae) . Overall, trovafloxacin and ciprofloxacin activities were similar for Haemophilus influenzae, Moraxella catarrhalis and Klebsiella pneumoniae isolates . Of the Streptococcus pneumoniae isolates, 6% were resistant to penicillin . Trovafloxacin had the highest activity against the Streptococcus pneumoniae isolates, with a minimum inhibitory concentration of 0.25 mg/l for 90% of isolates (MIC90); all strains tested were susceptible to trovafloxacin . The MIC90 of ciprofloxacin for Streptococcus pneumoniae was 3 mg/l, and overall 52% of the strains were susceptible; 9% were resistant . Azithromycin and clarithromycin exhibited similar activity against all collected pathogens, except Haemophilus influenzae . All strains of Haemophilus influenzae were susceptible to azithromycin compared with 79% for clarithromycin, with respective MIC90s of 2 and 16 mg/l . The data presented demonstrate differences in the susceptibility patterns of six major respiratory tract pathogens in Europe.

Am J Otolaryngol, 1998 Sep-Oct, 19(5), 301 - 4
Bacteria in the middle ear and nasopharynx during tympanostomy tube insertion; Clary RA et al.; PURPOSE: To evaluate the efficacy of nasopharyngeal cultures in identifying pathogens in middle-ear effusions as an alternative to cultures obtained through tympanocentesis . MATERIALS AND METHODS: The study population consisted of 203 children with middle-ear effusions at the time of placement of tympanostomy tubes for recurrent otitis media or persistent otitis media with effusion . Isolates from the nasopharynx were compared with those from the middle ear to determine sensitivity, specificity, and predictive values for each of the three main pathogens . RESULTS: The predominant bacterial isolates from both ear and nasopharynx were Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae . Eighty-one percent (42% highly, 39% relatively) S pneumoniae nasopharyngeal isolates were resistant to penicillin . The negative predictive value of the nasopharyngeal cultures was at least 97% for each of these predominant bacteria . CONCLUSION: This study supports the conclusion that tympanocentesis is the most useful means of identifying pathogens in otitis media.

Otolaryngol Pol, 1997, 51 Suppl 25, 179 - 83
{Bacterial flora in chronic purulent maxillary sinusitis}; Ziuzio S et al.; In the years from 1993 till 1995 there were 132 tests done on occurrence aerobes (oxygen bacteria) and 56 tests on occurrence of anaerobes and fungus in patients with chronic sinusitis . The most common microorganisms among the aerobes was Haemophilus influenzae (23.1%) and Staphylococcus aureus (20.9%) . The most common microorganisms among the anaerobes was Peptococcus and Peptostreptococcus (together 57.1%) and from the strains Bacteroides (36.8) . The breeded oxygen microorganisms Gr(+) were mostly sensible to clindamycin, cefuroxim and augmentin; Gr(-) organisms to amicacin, gentamycin and cefuroxim . Anaerobes were mostly sensible to metronidazole and clindamycin.

Antimicrob Agents Chemother, 1998 Oct, 42(10), 2690 - 3
Haemophilus ducreyi is susceptible to protegrin; Fortney K et al.; Protegrins, potent antimicrobial peptides found in porcine leukocytes, have activity against the sexually transmitted pathogens Neisseria gonorrhoeae, Chlamydia trachomatis, and human immunodeficiency virus type 1 . We tested synthetic protegrin 1 (PG-1) for activity against nine isolates of Haemophilus ducreyi, the etiologic agent of chancroid . The test organisms included CIP 542 (the type strain), 35000HP (a human-passaged variant of 35000), 35000HP-RSM2 (an isogenic D-glycero-D-manno-heptosyltransferase mutant of 35000HP), and six clinical isolates . The isolates were epidemiologically unrelated, represented three HindIII ribotypes, and had varying antimicrobial resistance patterns . In bactericidal assays, five isolates were rapidly killed by synthetic PG-1 . In radial diffusion assays, all nine isolates were exquisitely sensitive to PG-1 . These data highlight the potential of protegrins for development as topical agents to prevent many sexually transmitted diseases, including chancroid.

Jpn J Antibiot, 1998 Jun, 51(6), 413 - 31
{Basic and clinical studies on tazobactam/piperacillin in pediatric field}; Motohiro T et al.; A drug susceptibility test of the combination drug TAZ/PIPC, which consists of a newly developed beta-lactamase inhibitor, tazobactam (TAZ), and one of penicillin antibiotics, piperacillin (PIPC), with combination ratio of 1:4 in potency, was conducted with stock strains and clinical isolates . The clinical efficacy and safety of its injection was also evaluated in children with a variety of infectious diseases . The results were as follows: 1 . In susceptibility test, 114 strains from 4 species of stock strains were treated with 8 drugs, that is, TAZ/PIPC, PIPC, penicillin G (PCG), ampicillin (ABPC), cefotiam (CTM), cefotaxime (CTX), ceftazidime (CAZ), and sulbactam/cefoperazone (SBT/CPZ) . Of three clinically isolated species from patients, Staphylococcus aureus (S . aureus) was treated with TAZ/PIPC, PIPC, methicillin (DMPPC), CTM, CTX, and SBT/CPZ, and the others were treated with the same drugs except for DMPPC . The MICs were measured for these bacterial strains inoculated at the concentration of 10(6) CFU/ml . The MIC90 values of TAZ/PIPC against 45 strains of Streptococcus pyogenes (S . pyogenes), one of the stock cultures of Gram-positive cocci, were 0.05 microgram/ml and similar to those of PIPC, CTM, CAZ, and SBT/CPZ . The MICs of TAZ/PIPC for 28 strains of Streptococcus agalactiae (S . agalactiae) were 0.39 microgram/ml and similar to those of PIPC, CTM, CAZ, and SBT/CPZ . As for Gram-negative bacilli, the MIC90 of TAZ/PIPC against 10 strains of Bordetella pertussis (B . pertussis) were 0.10 microgram/ml and similar to those of PIPC . The MIC90 of TAZ/PIPC against 31 strains of Haemophilus influenzae (H . influenzae) were 0.05 microgram/ml and similar to those of PIPC, CTX, and SBT/CPZ . Regarding Gram-positive cocci isolated from patients received this combination drug, the MIC90 of TAZ/PIPC against 2 strains of S . aureus, a non beta-lactamase producing strain and a low-beta-lactamase producing strain, were 0.78 microgram/ml and 3.1 micrograms/ml, respectively; the former value was similar to those of PIPC, DMPPC, CTM, and CTX, and the latter was similar to those of PIPC, DMPPC, CTX, and SBT/CPZ . Of 4 strains of Streptococcus pneumoniae, 2 strains were inhibited at 0.05 microgram/ml, and the others at 1.56 micrograms/ml; both values were similar to those of PIPC, SBT/CPZ . As for Gram-negative bacilli, 6 of 7 strains of H . influenzae did not produce beta-lactamase and 1 strain was a high producer . The MICs of TAZ/PIPC against beta-lactamase nonproducing strains were < or = 0.025 microgram/ml in 5 strains and 0.39 microgram/ml in 1 strain, and the values were similar to those of PIPC and SBT/CPZ . While the MIC of TAZ/PIPC against the high beta-lactamase producing strain was 0.78 microgram/ml; similar to that of SBT/CPZ and smaller than that of PIPC . 2 . The results of clinical effects on 7 diseases in 33 cases were as follows: TAZ/PIPC was clinically judged "excellent" in 17 (51.5%); good in 14 (42.4%); fair in 2 (6.1%) . No case with no response was seen in this study, and the total efficacy rate of "excellent" and "good" was 93.9% . 3 . Bacteriological effects were evaluated in 17 strains of 4 species, and all of them were eradicated . 4 . Adverse reactions were judged in 35, which consisted of 33 in which the clinical effects were evaluated and 2 dropped from this study . Of these cases, diarrhea was observed in 4 (11.4%) . 5 . Laboratory tests revealed an increase in platelets in 1 of 32 cases (3.1%), and eosinophilia in 2 of 29 cases (6.9%) . Biochemical profile showed an increase in GPT alone and abnormal increases in both GOT and GPT in 1 each out of 21 cases.

Jpn J Antibiot, 1998 Jun, 51(6), 395 - 406
{Laboratory and clinical studies on tazobactam/piperacillin in the field of pediatrics}; Kuno K et al.; Laboratory and clinical studies on tazobactam/piperacillin (TAZ/PIPC), a combination drug of piperacillin (PIPC) with the new beta-lactamase inhibitor tazobactam (TAZ), were carried out in the field of pediatrics . 1 . After intravenous administration of TAZ/PIPC at a dose of 25 mg/kg to one child, the peak plasma levels of TAZ and PIPC were 24.4 micrograms/ml and 119 micrograms/ml respectively after 5 min . The half-lives of TAZ and PIPC were 0.48 and 0.60 hours respectively . Same as 50 mg/kg to two children, the peak plasma levels of TAZ and PIPC were 17.5, 32.2 micrograms/ml and 92.8, 163 micrograms/ml after 5 min . The half-lives of TAZ and PIPC were 0.37, 0.50 hours and 0.51, 0.59 hours . A ratio of TAZ to PIPC was about 1 to 4 in plasma levels . The cumulative urinary recovery rates of TAZ and PIPC in the first 6 hours after intravenous administration were 15.8, 64.9% and 39.8, 53.4% . 2 . The antibacterial activity of TAZ/PIPC against clinically isolated organisms was determined . The MICs of TAZ/PIPC were < or = 0.05 microgram/ml against Haemophilus influenzae and Streptococcus pneumoniae and > or = 1.56 micrograms/ml against Escherichia coli, Staphylococcus aureus and Haemophilus parainfluenzae . 3 . The clinical efficacy of TAZ/PIPC could be evaluated in 14 patients with various bacterial infections, and was evaluated as "excellent" in 9 patients and as "good" in 5 . The overall clinical efficacy rate in 14 cases was 100% and excellent was 64.3% . Bacteriological efficacy rate was 91.7% (10/11) . 4 . As a side effect, loose stool was observed in one case, no abnormal laboratory test values were observed . It has been concluded that TAZ/PIPC was a useful drug in the field of pediatrics.

Jpn J Antibiot, 1998 Jul, 51(7), 437 - 74
{Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (1996)}; Ikemoto H et al.; The bacteria isolated from the patients with lower respiratory tract infections were collected by institutions located throughout Japan, since 1981 . Ikemoto et al . have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and characteristics of the patients and isolates from them each year . Results obtained from these investigations are discussed . In 16 institutions around the entire Japan, 557 strains of presumably etiological bacteria were isolated mainly from the sputa of 449 patients with lower respiratory tract infections during the period from October 1996 to September 1997 . MICs of various antibacterial agents and antibiotics were determined against 98 strains of Staphylococcus aureus, 93 strains of Streptococcus pneumoniae, 84 strains of Haemophilus influenzae, 84 strains of Pseudomonas aeruginosa (non-mucoid strains), 17 strains of Pseudomonas aeruginosa (mucoid strains), 31 strains of Moraxella subgenus Branhamella catarrhalis, 21 strains of Klebsiella pneumoniae etc., and the drug susceptibilities of these strains were assessed except for those strains that died during transportation . 1) S . aureus S . aureus strains for which MICs of oxacillin (MPIPC) were higher than 4 micrograms/ml (methicillin-resistant S . aureus) accounted for 67.3% . The frequency of the drug resistant bacteria increased comparing to the previous year's 52.7% . Arbekacin (ABK) and vancomycin (VCM) showed the highest activities against both S . aureus and MRSA with MIC80s of 1 microgram/ml . 2) S . pneumoniae Imipenem (IPM) and panipenem (PAPM) of carbapenems showed the most potent activities with MIC80s of 0.063 microgram/ml . Faropenem (FRPM) showed the next potent activity with MIC80 of 0.125 microgram/ml . The other drugs except erythromycin (EM), clindamycin (CLDM) and tetracycline (TC) were active against S . pneumoniae tested with MIC80s of 8 micrograms/ml or below . 3) H . influenzae The activities of all drugs were potent against H . influenzae tested with MIC80s of 4 micrograms/ml or below . Cefotiam (CTM), cefmenoxime (CMX), cefditoren (CDTR) and ofloxacin (OFLX) showed the most potent activities with MIC80s of 0.063 microgram/ml . 4) P . aeruginosa (mucoid strains) Tobramycin (TOB) showed the most potent activity against P . aeruginosa (mucoid strains) with MIC80 of 1 microgram/ml . Ceftazidime (CAZ), cefsulodin (CFS), IPM, gentamicin (GM), ABK and ciprofloxacin (CPFX) showed the next potent activities, with MIC80s of 2 micrograms/ml . The MIC80s of the other drugs ranged from 4 micrograms/ml to 16 micrograms/ml . 5) P . aeruginosa (non-mucoid strains) TOB and CPFX showed the most potent activities against P . aeruginosa (non-mucoid strains) with MIC80s of 1 microgram/ml . The MIC80s of piperacillin (PIPC) and cefoperazone (CPZ) were 16 micrograms/ml in 1995, and they were 64 micrograms/ml in 1996 . 6) K . pneumoniae All drugs except ampicillin (ABPC) were active against K . pneumoniae . CMX, cefpirome (CPR), cefozopran (CZOP) and carumonam (CRMN) showed the most potent activities against K . pneumoniae with MIC80s of 0.125 microgram/ml . The MIC80s of the other drugs ranged from 0.25 microgram/ml to 2 micrograms/ml . 7) M.(B) catarrhalis Against M.(B.) catarrhalis, all drugs showed good activities with MICs of 4 micrograms/ml or below . IPM and minocycline (MINO) showed the most potent activities with MICs of 0.063 microgram/ml . Also, we investigated year to year changes in the characteristics of patients, their respiratory infectious diseases, and the etiology . Patients' backgrounds were examined for 557 isolates from 449 cases . The examination of age distribution indicated that the proportion of patients with ages over 60 years was 71.0% of all the patients showing a slight increase over that in 1994 . Proportions of diagnosed diseases were as follows: Bacterial pneumonia and chronic bronchitis were the most frequent with 35.9% and 30.3% respectively . They were followed by bronchiectasis with a proportion of 10.

J Mass Spectrom, 1998 Aug, 33(8), 750 - 6
Rapid identification and speciation of Haemophilus bacteria by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; Haag AM et al.; Several species of the genus Haemophilus are well known etiological agents of pneumonia, meningitis, conjunctivitis, epiglottitis and chancroid . However, identification and speciation of Haemophilus is both time consuming and labor intensive . Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI/TOF-MS) has been used by several investigators to profile proteins from intact and disrupted bacteria; consequently, MALDI/TOF-MS has emerged as a powerful tool in diagnostic bacteriology . This paper reports the use of MALDI/TOF-MS as a technique for the rapid identification and speciation of Haemophilus . This technique was used to not only identify the pathogen, H . ducreyi, but also to determine strain differences from different isolates . Mass spectral 'fingerprints' were obtained which permitted the rapid speciation of not only pathogenic forms of Haemophilus, but also those bacteria which are normally regarded as non-pathogenic and members of the normal flora . MALDI/TOF mass spectra can be acquired in 10 min, allowing the identification of Haemophilus spp . within 24 h rather than the 48 h or more needed for traditional bacteriological methods . In addition, these are the first mass spectral fingerprints available in the literature for many of these organisms.

Medscape Womens Health . 1996 Jun;1(6):4.
Haemophilus influenzae Genome: After Sequencing, Then What?
Redfield RJ.
Haemophilus influenzae is an important human pathogen that causes a number of chronic and acute infections--notably, life-threatening bacteremia and meningitis in infants and community-acquired pneumonia in adults . The technological feat of sequencing the entire H influenzae genome was completed less than a year ago . Now that the genetic instruction manual is available, the task of deciphering its meaning has begun . This search will be a lengthy one, but it holds the promise of finding new ways to prevent, detect, and treat disease . The information gained will also shed light on mechanisms used by other bacterial pathogens and help to increase our understanding of how they cause disease.

Infect Immun, 1998 Oct, 66(10), 5008 - 19
The cell cycle-specific growth-inhibitory factor produced by Actinobacillus actinomycetemcomitans is a cytolethal distending toxin; Sugai M et al.; Actinobacillus actinomycetemcomitans has been shown to produce a soluble cytotoxic factor(s) distinct from leukotoxin . We have identified in A . actinomycetemcomitans Y4 a cluster of genes encoding a cytolethal distending toxin (CDT) . This new member of the CDT family is similar to the CDT produced by Haemophilus ducreyi . The CDT from A . actinomycetemcomitans was produced in Escherichia coli and was able to induce cell distension, growth arrest in G2/M phase, nucleus swelling, and chromatin fragmentation in HeLa cells . The three proteins, CDTA, -B and -C, encoded by the cdt locus were all required for toxin activity . Antiserum raised against recombinant CDTC completely inhibited the cytotoxic activity of culture supernatant and cell homogenate fractions of A . actinomycetemcomitans Y4 . These results strongly suggest that the CDT is responsible for the cytotoxic activity present in the culture supernatant and cell homogenate fractions of A . actinomycetemcomitans Y4 . This CDT is a new putative virulence factor of A . actinomycetemcomitans and may play a role in the pathogenesis of periodontal diseases.

Infect Immun, 1998 Oct, 66(10), 4788 - 96
Immunologic and structural relationships of the minor pilus subunits among Haemophilus influenzae isolates; McCrea KW et al.; Two proteins, HifD and HifE, have been identified as structural components of Haemophilus influenzae pili . Both are localized at the pilus tip, and HifE appears to mediate pilus adherence to host cells . In this study we examined the immunologic and structural diversity of these pilus subunits among type b H . influenzae (Hib) and nontypeable H . influenzae (NTHI) strains . Western immunoblot analysis revealed that antibodies directed against the C terminus of HifD and HifE from Hib strain Eagan bound to HifD and HifE proteins, respectively, of all piliated Hib and NTHI strains tested . Whole-cell enzyme-linked immunosorbent assays showed that antibodies specific for native HifD or HifE of strain Eagan also bound to all piliated Hib strains but did not bind to the piliated NTHI strains . Antibodies against HifE of strain Eagan inhibited the binding of Hib to human erythrocytes but did not inhibit the binding of NTHI strains . Restriction fragment length polymorphism (RFLP) analysis was used to determine strain-to-strain structural differences within hifD and hifE genes, either by PCR or by nucleotide sequence analysis . DNA and derived amino acid sequence analyses of HifD and HifE confirmed the uniqueness of the RFLP types . The hifD and hifE genes of all type b strains showed identical restriction patterns . Analysis of hifD and hifE genes from the NTHI strains, however, revealed seven unique RFLP patterns, suggesting that these genes encode proteins with diverse primary structures . These results indicate that HifD and HifE are immunologically and structurally similar among the Hib strains but vary among the NTHI strains.

Infect Immun, 1998 Oct, 66(10), 4733 - 41
hgpB, a gene encoding a second Haemophilus influenzae hemoglobin- and hemoglobin-haptoglobin-binding protein; Ren Z et al.; Haemophilus influenzae requires heme for growth and can utilize both hemoglobin and hemoglobin-haptoglobin as heme sources . We previously identified a hemoglobin- and hemoglobin-haptoglobin-binding protein, HgpA, in H . influenzae HI689 . Mutation of hgpA did not affect binding or utilization of either heme source . The hgpA mutant exhibited loss of a 120-kDa protein and increased expression of a 115-kDa protein . These data suggested that at least one other gene product is involved in binding of these heme sources by H . influenzae . A 3.2-kbp PCR product derived from HI689 was cloned . The nucleotide sequence indicated a separate, distinct gene with high homology to hgpA, which would encode a 115-kDa protein . Primers were designed for directional cloning of the structural gene in the correct reading frame . Sonicates of induced Escherichia coli harboring the cloned open reading frame bound both hemoglobin and hemoglobin-haptoglobin . An insertion/deletion mutant of H . influenzae at the newly identified locus, designated hgpB, was constructed . The 115-kDa protein was not detected in the mutant after affinity purification using biotinylated hemoglobin . An hgpA hgpB double-mutant strain exhibited a reduced ability to utilize hemoglobin-haptoglobin, although it was unaltered in the ability to utilize hemoglobin . Affinity isolation of hemoglobin-binding proteins from the double mutant resulted in isolation of an approximately 120-kDa protein . Internal peptide sequencing revealed this protein to be a third distinct protein, highly homologous to HgpA and HgpB . In summary a second hemoglobin- and hemoglobin-haptoglobin-binding protein of H . influenzae has been identified and characterized, and the presence of an additional protein of similar function has been revealed.

MMWR Morb Mortal Wkly Rep, 1998 Sep 11, 47(35), 737 - 40
Haemophilus influenzae invasive disease among children aged <5 years--California, 1990-1996.
{An epidemiological investigation for MRSA and PRSP in Kinki area . Kinki Infection Working Group}
Mikasa K, Sawaki M, Konishi M, Maeda K, Tsujimoto M, Mori K, Narita N, Koizumi A, Sano R, Masutani T.

Second Department of Internal Medicine, Nara Medical UniversityRecent trends in the development of resistance of the Staphylococcus aureus and Streptococcus pneumoniae to antibiotics were investigated, using a questionnaire delivered to participants at a meeting of the Kinki District Society of Infections . Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 55.4% of all isolated S . aureus, and more than 80% of MRSA was detected within hospitals . In outpatients, MRSA was often detected in pus, while in hospitalized patients, MRSA was often detected in sputum . Further, MRSA was accompanied by some other organisms (most frequently Pseudomonas aeruginosa) in 64.7% of MRSA positive patients . The sensitivity of MRSA to vancomycin (VCM) was 100%, to sulfamethoxazole-trimethoprim (ST) 99.2%, and to arbekacin, 98.6% . In contrast, Penicillin-resistant Streptococcus pneumoniae (PRSP) accounted for 42.4% of all isolates of Streptococcus pneumoniae . About 50% of PRSP was detected in out-patients . For both hospitalized patients and outpatients, PRSP was most frequently detected in sputum . PRSP was accompanied by some other organisms (most frequently Haemophilus influenzae) in 49.3% of PRSP positive patients, PRSP had high sensitivity to cephems, carbapenems and VCM.

APMIS, 1998 Aug, 106(8), 800 - 6
Antibody responses in serum and lung to intranasal immunization with Haemophilus influenzae type b polysaccharide conjugated to cholera toxin B subunit and tetanus toxoid; Bergquist C et al.; AIM: Cholera toxin B subunit (CTB) has previously been used as a mucosal carrier for various vaccine candidate antigens . The objective of this study was to see if coupling a bacterial polysaccharide, Haemophilus influenzae type b capsular polysaccharide (HibCPS), to CTB, either directly or through prior coupling to tetanus toxoid (TT), would improve the immunogenicity of HibCPS after nasal immunization . METHODS: HibCPS was conjugated to CTB, TT or via TT to CTB, using glutaraldehyde or 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide (EDAC) and N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) . The conjugates were characterized and used for intranasal (IN) and subcutaneous (SC) immunizations of mice . The anti-Hib, -TT and -CTB antibody titers in serum and lungs after the immunizations were measured with ELISA . RESULTS: The HibCTB was poorly immunogenic both given IN and SC compared with HibTT and HibTTCTB, probably because of inefficient coupling . In contrast, the conjugation of CTB to the HibTT conjugate resulted in a preparation which was superior both to the HibTT and the HibCTB conjugates in inducing local IgA and IgG anti-HibCPS antibodies in the lungs . The anti-HibCPS serum IgG titers after IN immunization with the HibTTCTB conjugate were similar to the titers after IN immunization with HibTT, or SC immunization with a commercial HibCRM conjugate vaccine . In contrast to the other conjugates, the HibTTCTB conjugate also gave rise to anti-Hib serum IgA titers . CONCLUSION: We conclude that appropriate conjugation to CTB increases the mucosal immunogenicity of HibCPS, and that intranasal immunization with such a conjugate can give rise to both local and systemic anti-HibCPS antibody responses.

Jpn J Antibiot, 1997 Jul, 50(7), 597 - 621
{Pharmacokinetic and clinical studies with cefluprenam in the pediatric field . Pediatric Study Group of Gefluprenam}; Fujii R et al.; Evaluation of efficacy and safety of cefluprenam (code number: E1077, abbreviation: CFLP), a newly developed injectable cephem antibiotics was conducted on adult patients with various infections, and followed by the study group organized from 39 institutions in pediatric field, as the drug showed no toxicity problems in suckling animals . Informed consents from legal representatives were obtained prior to the study . 1 . Clinical efficacy . Two-hundred eighty one cases were included for analysis of clinical efficacy after 40 cases of exclusion or drop-out were subtracted from a total of 321 cases . However, the cumulative number of cases evaluable for analysis was considered to be 289, because 8 cases that had 2 different diseases at the same time were counted in each category of disease . In the cases in which causative organisms were identified (group A), 148 of 154 cases were rated as good or excellent, with an efficacy rate of 96.1% . As for clinical efficacies by disease, efficacy rates were 6/6 for purulent meningitis, 4/5 for sepsis, 95.7% (62/65) for pneumonia, 100.0% (29/29) for urinary tract infections, and 94.1% (16/17) for skin and soft tissue infections . The rate of excellent responses among excellent and good responses was 73.6% (109/148), showing a higher value than any of recent injectable beta-lactams . On 32 cases with S . pneumoniae infection, the efficacy rate of CFLP was 100.0% . In the cases where causative organisms were not identified (group B), 128 of 135 cases were rated as good or excellent, with an efficacy rate of 94.8% . In the all cases including both the group A and the group B, the efficacy rate was 95.2% (276/289) and the rate of excellent responses among excellent and good response was 70.7% (195/276) . Against severe infections, CFLP exhibited excellent clinical efficacy, showing an efficacy rate of 8/8 for meningitis, 3/5 for sepsis and 100.0% (22/22) for severe pneumonia . As for bacteriological responses, eradication rates were 95.2% (177/186) in total . Against Gram-positive cocci, the eradication rate was 92.7% (76/82), with eradication rates of 94.3% (33/35) for Staphylococcus aureus, and 93.3% (28/30) for Streptococcus pneumoniae . Against Gram-negative rods, the eradication rate was 97.1% (101/104), and eradication rates were 100.0% (22/22) for Escherichia coli, 97.5% (39/40) for Haemophilus influenzae and 100.0% (19/19) for Molaxella catarrhalis . In cases in which more than 3 days of treatment with previous chemotherapy resulted in no response, the efficacy rate of CFLP was 94.2% (98/104), rated excellent in 68 cases and good in 30 cases . In these cases, the eradication rate was 98.1% (52/53) . 2 . Pharmacokinetics . CFLP was intravenously administerrd to 12 subjects at doses of 20 to 40 mg (potency)/kg . In 9 subjects aged more than 12 months, maximum serum levels (Cmax), T 1/2 beta and AUC of CFLP were 155.3 +/- 9.8 micrograms/ml, 1.43 +/- 0.18 hours and 111.7 +/- 15.0 micrograms.hr/ml, respectively, when a dose of 20 mg (potency)/kg was used . In 2 subjects aged not more than 12 months, the mean Cmax, T 1/2 beta and AUC were 153 micrograms/ml, 1.6 hour and 81 micrograms.hr/ml, respectively, at a dose of 20 mg(potency)/kg . The mean Cmax, T 1/2 beta and AUC were 332 micrograms/ml, 0.93 hours and 157.3 micrograms.hr/ml, respectively, in 1 subject at a dose of 40 mg (potency)/kg . In 10 subjects dosed 20 mg (potency)/kg, urinary levels were 2413 +/- 512, 1471 +/- 524, and 470 +/- 115 micrograms/ml in 0-2, 2-4, and 4-6 hours after dosing, respectively, showing a cumulative urinary excretion rate of 61.4 +/- 6.3% . In 1 subject dosed 40 mg (potency)/kg, urinary levels were 5700 and 4770 micrograms/ml in 0-2 p3d 2-4 hours after dosing, respectively, showing a cumulative urinary excretion rate of 42.1% . Cerebrospinal fluid concentrations of CFLP, on 10 subjects with purulent meningitis dosed 40-103 mg (potency)/kg were 3.2-32.9 micrograms/ml at 0.5-2 hours after administration within 4 days after the onset of

J Immunol, 1998 Sep 15, 161(6), 2895 - 905
Clonal analysis of a human antibody response . III . Nucleotide sequences of monoclonal IgM, IgG, and IgA to rabies virus reveal restricted V kappa gene utilization, junctional V kappa J kappa and V lambda J lambda diversity, and somatic hypermutation; Ikematsu W et al.; In previous work, we generated four IgM, five IgG1, and one IgA1 mAbs to rabies virus using B cells from four subjects vaccinated with inactivated rabies virus, a thymus-dependent (TD) mosaic Ag, and sequenced the mAb V(H)DJ(H) genes . Here, we have cloned the V kappa J kappa and V lambda J lambda genes to complete the primary structure of the Ag-binding site of these mAbs . While the anti-rabies virus mAb selection of VA genes (2e.2.2 twice, DPL11, and DPL23) reflected the representation of the V lambda genes in the human haploid genome (stochastic utilization), that of V kappa genes (O2/O12 twice, O8/O18, A3/A19, A27, and L2) did not (p = 0.0018) (nonstochastic utilization) . Furthermore, the selection of both V kappa and V lambda genes by the anti-rabies virus mAbs vastly overlapped with that of 557 assorted V kappa J kappa rearrangements, that of 253 V lambda J lambda rearrangements in lambda-type gammopathies, and that of other Abs to thymus-dependent Ags, including 23 anti-HIV mAbs and 51 rheumatoid factors, but differed from that of 43 Abs to Haemophilus influenzae type b polysaccharide, a prototypic thymus-independent (TI) Ag . The anti-rabies virus mAb V kappa J kappa and V lambda J lambda segments displayed variable numbers of somatic mutations, which, in mAb58 and the virus-neutralizing mAb57, entailed a significant concentration of amino acid replacements in the complementarity-determining regions (p = 0.0028 and p = 0.0023, respectively), suggesting a selection by Ag . This Ag-dependent somatic selection process was superimposed on a somatic diversification process that occurred at the stage of B cell receptor for Ag rearrangement, and that entailed V gene 3' truncation and N nucleotide additions to yield heterogeneous CDR3s.

Nat Biotechnol, 1998 Sep, 16(9), 851 - 6
A genome-based approach for the identification of essential bacterial genes; Arigoni F et al.; We have used comparative genomics to identify 26 Escherichia coli open reading frames that are both of unknown function (hypothetical open reading frames or y-genes) and conserved in the compact genome of Mycoplasma genitalium . Not surprisingly, these genes are broadly conserved in the bacterial world . We used a markerless knockout strategy to screen for essential E . coli genes . To verify this phenotype, we constructed conditional mutants in genes for which no null mutants could be obtained . In total we identified six genes that are essential for E . coli (yhbZ, ygjD, ycfB, yfil, yihA, and yjeQ) . The respective orthologs of the genes yhbZ, ygjD, ycfB, yjeQ, and yihA are also essential in Bacillus subtilis . This low number of essential genes was unexpected and might be due to a characteristic of the versatile genomes of E . coli and B . subtilis that is comparable to the phenomenon of nonorthologous gene displacement . The gene ygjD, encoding a sialoglycoprotease, was eliminated from a minimal genome computationally derived from a comparison of the Haemophilus influenzae and M . genitalium genomes . We show that ygjD and its ortholog ydiE are essential in E . coli and B . subtilis, respectively . Thus, we include this gene in a minimal genome . This study systematically integrates comparative genomics and targeted gene disruptions to identify broadly conserved bacterial genes of unknown function required for survival on complex media.

Syst Appl Microbiol, 1998 Mar, 21(1), 50 - 64
Characterization of atypical Aeromonas salmonicida by different methods; Austin B et al.; Fifty two isolates of atypical Aeromonas salmonicida, recovered from a wide range of hosts and geographical locations, were heterogeneous in terms of molecular and phenotypic characteristics, and represented taxa which could not be accommodated by the current classification of four subspecies . Generally, there was incongruence between the molecular (PCR, RAPD and ribotyping) and phenotypic methods in terms of cluster membership . By PCR, 6 groups were described of which Group 1 encompassed 12 isolates including the type strain of A . salmonicida subsp . smithia . Group 2 accommodated 23 isolates including the reference cultures of subspecies achromogenes and masoucida . The named culture of Haemophilus piscium was recovered in Group 6 . By ribotyping and RAPD, the reference cultures were recovered in separate groups . All methods pointed to the uniqueness of subspecies smithia . Most isolates contained 2-6 plasmids, of 2.3 to 150 kb in length . Nevertheless, all isolates possessed certain key characteristics, including Gram-negativity, and the absence of motility.

Electrophoresis, 1998 Aug, 19(11), 1980 - 8
Strategies towards a better understanding of antibiotic action: folate pathway inhibition in Haemophilus influenzae as an example; Evers S et al.; Two-dimensional electrophoresis was applied to the global analysis of the cellular response of Haemophilus influenzae to sulfamethoxazole and trimethoprim, both inhibitors of tetrahydrofolate synthesis . Deregulation of the synthesis rate of 118 proteins, involved in different metabolic pathways, was observed . The regulation of the genes involved in the metabolism of the amino acids methionine, threonine, serine, glycine, and aspartate was investigated in detail by analysis of protein synthesis and Northern hybridization . The results suggested that the synthesis of methionine biosynthetic enzymes in H . influenzae is regulated in a similar fashion as in Escherichia coli . A good correlation between the results obtained by Northern hybridization and quantification of protein synthesis was observed . In contrast to trimethoprim, sulfamethoxazole triggered the increased synthesis of the heat shock proteins DnaK, GroEL, and GroES.

J Antimicrob Chemother, 1998 Aug, 42(2), 133 - 40
Interactions of plaunotol with bacterial membranes; Koga T et al.; Plaunotol, a cytoprotective antiulcer agent, has a bactericidal effect against Helicobacter pylori, which may result from interaction of this compound with the bacterial cell membrane . The purpose of the present study was to confirm that plaunotol interacts with the H . pylori membrane . Membrane fluidities were measured using two stearic acid spin labels, namely 5-doxyl-stearic acid (in which the nitroxide group is located in the upper portion of the bacterial cell membrane) and 16-doxyl-stearic acid methyl ester (in which the nitroxide group is located deeper in the bacterial cell membrane), by means of electron spin resonance . The membrane fluidities of plaunotol-treated cells were significantly increased in the measurements made using the two spin labels . We also attempted to isolate plaunotol-resistant H . pylori in vitro by two different methods . To assess the level of resistance that could be reached, H . pylori was passaged five times on an agar plate containing subinhibitory concentrations of plaunotol or metronidazole . To measure the rate of development of resistance, H . pylori was grown with subinhibitory concentrations (0.25 x MIC) of plaunotol or metronidazole, and quantitatively plated on to medium containing 4 x MIC of the compounds . This treatment was repeated once more . No plaunotol-resistant colonies were selected by the two methods . H . pylori developed resistance to metronidazole easily and at a relatively high rate . The mechanism by which plaunotol directly fluidizes and destroys the H . pylori membrane might make it difficult for this organism to develop resistance to plaunotol . It was confirmed that the bactericidal effects of plaunotol were also shown against Staphylococcus aureus, Streptococcus pneumoniae, Neisseria gonorrhoeae, Moraxella catarrhalis and Haemophilus influenzae . No such effect was seen against Escherichia coli and Pseudomonas aeruginosa.

Przegl Epidemiol, 1998, 52(1-2), 199 - 203
{The penicillin susceptibility of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus in persons suffering from upper respiratory tract infections}; Harenska K et al.; The susceptibility to penicillin was tested in 293 strains of S . aureus, 162 strains of H . influenzae, 60 strains of M . catarrhalis and 77 strains of S . pneumoniae, isolated from persons suffering from upper respiratory tract infections . Penicillin susceptibility testing has been performed by the disc diffusion technique . Beta-lactamase production in the penicillin-resistant strains of H . influenzae, M . catarrhalis and S . aureus was detected with nitrocefin impregnated disc . In beta-lactamase positive strains, the susceptibility to amoxacillin/clavulanic acid (AMC) was determined . Nearly half (46.3%) of H . influenzae strains was resistan to ampicillin . In the remaining bacteria, the percentage of resistance was 2.6% for S . pneumoniae, 82.4% for M . catarrhalis and 88.1% for S . aureus strains . All strains resistant to penicillin (ampicillin) produced beta-lactamase and were AMC sensitive.

Antimicrob Agents Chemother, 1998 Sep, 42(9), 2385 - 90
Dynamics of clarithromycin and azithromycin efficacies against experimental Haemophilus influenzae pulmonary infection; Alder JD et al.; The dynamics of clarithromycin and azithromycin efficacy against pulmonary Haemophilus influenzae infection in rats were evaluated . Efficacy was measured by reduction in pulmonary H . influenzae burden on days 3 and 7 postinoculation . Clarithromycin therapy was effective on day 3 or 7 of therapy, while azithromycin was effective on day 7 but not on day 3 of therapy . Both macrolides produced marked efficacy against all six strains of H . influenzae tested, including four strains for which MICs were above the susceptible breakpoint (8 microgram/ml) concentration of clarithromycin . The two macrolides demonstrated markedly different pharmacokinetic characteristics, with clarithromycin present in both blood and tissue, while azithromycin was concentrated primarily in tissue . During pulmonary infection in rats, H . influenzae was found in both intracellular locations and an extracellular location in the lung . Blood concentrations of clarithromycin and azithromycin approximated human pharmacokinetics, and the blood concentrations for either macrolide rarely exceeded MICs for H . influenzae . At dosages producing blood concentrations similar to values achieved clinically, clarithromycin produced efficacy on day 3 of therapy, while both clarithromycin and azithromycin were equally effective on day 7 . The different dynamics of clarithromycin and azithromycin suggest that length of therapy should be considered as a key parameter in evaluations of drug efficacy.

Antimicrob Agents Chemother, 1998 Sep, 42(9), 2365 - 70
In vitro pharmacodynamic studies of L-749,345 in comparison with imipenem and ceftriaxone against gram-positive and gram-negative bacteria; Odenholt I et al.; L-749,345 is a new parenteral carbapenem with a very long half-life similar to that of ceftriaxone . The aim of the present study was to investigate different pharmacodynamic parameters of L-749,345 in comparison with those of ceftriaxone and imipenem . The following studies were performed: (i) comparative studies of the MICs of L-749, 345, imipenem, and ceftriaxone for 70 strains of gram-positive and gram-negative bacteria; (ii) comparative studies of the rate of killing of gram-positive and gram-negative bacteria by L-749,345, imipenem, and ceftriaxone; (iii) studies of the postantibiotic effects of L-749,345, imipenem, and ceftriaxone; and (iv) studies of the postantibiotic sub-MIC effects of L-749,345, imipenem, and ceftriaxone . Significantly lower MICs of L-749,345 compared with those of ceftriaxone were found for all gram-negative organisms except Haemophilus influenzae . The MICs of L-749,345 were similar to those of imipenem for all organisms except Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus, for which the MICs of L-749,345 were higher . A concentration-dependent killing of methicillin-resistant S . aureus but not methicillin-susceptible strains was noted for both L-749,345 and imipenem . All three of the investigated drugs exhibited a postantibiotic effect against the gram-positive strains but exhibited no postantibiotic effect against the gram-negative strains.

Trop Med Int Health, 1998 Aug, 3(8), 610 - 8
Acute bacterial meningitis in children admitted to the Queen Elizabeth Central Hospital, Blantyre, Malawi in 1996-97; Molyneux E et al.; To design appropriate interventions, we collected clinical and demographic data prospectively on all children aged one day to 14 years admitted with a diagnosis of bacterial meningitis (BM) from April 1st 1996 to March 31st 1997 to the Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi . During the study period 267 children (2.7% of all paediatric admissions) were found to have BM; 83% were under 5 years of age, 61% under one year and 23% under one month . The most common causative organisms in the post neonatal period (n=206) were Streptococcus pneumoniae (27%), Haemophilus influenzae type b (Hib) 21%, and Salmonella typhimurium (6%) . In the neonatal group (< 1 month, n=61) the most common causes were Streptococcus agalactiae (23%), S . typhimurium (15%), S . pneumoniae (11.5%) and other Gram negative rods (11.5%) . Nineteen of 21 salmonella infections were in children under one year of age and all S . agalactiae were in infants under three months . There was delay on presentation: the average length of fever was 4.6 days, 39.5% had convulsed prior to arrival and 57% had an altered level of consciousness . An initial diagnosis of malaria had probably contributed to the delay in 22.5% (42 of 186 tested) . 48% were < 80% weight for age, with 18% < 60%) weight for age . The overall mortality was 40% . The outcome was worst in salmonella infections, particularly neonatal salmonella BM with a case fatality rate (CFR) of 89% (8 of 9 cases) . Coma on presentation worsened prognosis (mortality 64% if Blantyre Coma Score < 3, 26% if > 3) . 15% of survivors had sequelae on discharge . 20% of Hib isolates were resistant to chloramphenicol, but all salmonellae were sensitive . 5% of S . pneumoniae were resistant to penicillin and 8% to chloramphenicol . Earlier access to adequate health care and awareness of BM in a malaria-endemic area would reduce mortality and morbidity . Vaccination against Hib infection would have reduced death by 18 (17%) and prevented sequelae in 7 cases.

Scand J Infect Dis, 1998, 30(2), 165 - 8
Epidemiology of invasive Haemophilus influenzae type b infections among children in Greece before the introduction of immunization; Tsolia MN et al.; We prospectively examined the epidemiology of invasive Haemophilus influenzae type b (Hib) infections among children under 5 y of age in the Greater Athens area before the introduction of immunization . The annual incidence of systemic Hib infections was 12/100000 . Meningitis was the most common clinical entity and accounted for 69% of the cases . In the prevaccine era, the incidence of systemic Hib disease, particularly that of meningitis, was much lower in Greece compared to rates reported from Northern and Central Europe.

Clin Diagn Lab Immunol, 1998 Sep, 5(5), 667 - 74
A competitive enzyme-linked immunosorbent assay for measuring the levels of serum antibody to Haemophilus influenzae type b; Mariani M et al.; A competitive ELISA method is described for the measurement of total antibodies to the capsular polysaccharide of Haemophilus influenzae type b (HibCPS) in human sera . The competitive method showed an excellent correlation to the radioantigen binding assay (RABA, or Farr assay) and improved correlation of sera with low titers with respect to the more conventional noncompetitive method . Overestimation of samples in the low concentration range was no longer observed with the competitive ELISA method . The free HibCPS competition allowed us to eliminate the day-to-day background variation typical of some sera; thus, only values representing the true anti-HibCPS response were determined . The use of precoated microplates, which could be stored up to 8 months, greatly improved the speed of the procedure . An overall correlation coefficient of 0 . 9660 was found when 407 serum samples with a wide variety of anti-HibCPS antibody levels were tested with the competitive ELISA and RABA . The regression line was very close to the ideal line, with a slope of 1.0045 and an intercept of -0.1996 . A subset of 96 serum samples representative of all pre- and postimmunization samples was used to compare the competitive ELISA with a previously described ELISA method . The competitive method performed in two laboratories in different countries showed a better correlation with the RABA . The correlation factors were 0.9770 and 0.9816, respectively, while a factor of 0.9547 was found with the previously described noncompetitive procedure, which was better for this method than previously reported (r = 0.917) . Therefore, the competitive ELISA is proposed for the assay of anti-HibCPS titers in sera from vaccinated subjects.

Gene, 1998 Aug 31, 216(2), 285 - 92
Correlation of chi orientation with transcription indicates a fundamental relationship between recombination and transcription; Bell SJ et al.; Cross-over hot-spot instigator (Chi) sequences (5'-GCTGGTGG-3') are abundant, strand-specific, sequences, which locally increase recombination in Escherichia coli . Located within G-rich 'recombination islands', Chi orientations correlate with the orientations both of DNA replication and of transcription . Consistent with evidence from eukaryotic systems for a fundamental relationship between recombination and transcription, we find for E . coli Chi sequences, and for Haemophilus influenzae Chi-like sequences, that orientations correlate better with transcription than with replication . Complying with Szybalski's transcription direction rule, open reading frames in these prokaryotes have purine-rich mRNA-synonymous DNA strands . Hence, the G-richness of 'recombination islands' may reflect their correspondence with 'transcriptional islands' (genes) . Comparison of a natural with the corresponding shuffled sequence, indicates a base order-dependent island unit of approx . 1kb . 1998 Elsevier Science B.V.

Respir Med, 1993 May, 87(4), 303 - 8
Bacteriology of tonsil and adenoid and sampling techniques of adenoidal bacteriology; Gaffney RJ et al.; The value of pernasal swabs and direct adenoid swabs in chronic adenoid and adenotonsillar disease was assessed in 175 patients . Prior to adenoidectomy (53 patients) or adenotonsillectomy (122 patients), pernasal and direct adenoid swabs were taken . Adenoid currettings and tonsil tissue were cultured . Haemophilus influenzae was the bacterium most frequently isolated from adenoid currettings and from the centre (core) of the resected tonsil . There was a close relationship between the bacteriology of the pernasal swab and the adenoid tissue and tonsil core in 72 and 71% of patients, respectively . There was an identical profile of pathogens in 52 and 49%, respectively . We suggest that in children with adenoiditis or adenotonsillitis and hypertrophy of the adenoid, a pernasal swab should be used in preference to a throat swab in selecting appropriate antimicrobial therapy . Penicillin and ampicillin are not appropriate blind therapy in chronic adenoid and adenotonsillar infections because of the prevalence of beta-lactamase-producing aerobes (40%) in adenoid and tonsil core in these conditions.

Pediatr Infect Dis J, 1998 Aug, 17(8 Suppl), S83 - 8
Treatment of upper and lower respiratory tract infections: clinical trials with cefprozil; Aronovitz G; The oral second generation cephalosporin cefprozil has a broad spectrum microbiologic profile, with good in vitro activity against respiratory pathogens; 90% or more of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolates are susceptible to cefprozil . Clinical trials of cefprozil have consistently demonstrated good clinical success rates in upper and lower respiratory tract infections, including otitis media, sinusitis, pharyngitis/ tonsillitis and acute bacterial exacerbations of chronic bronchitis . Most recently cefprozil has demonstrated success in children with recurrent and persistent acute otitis media . Data from clinical trials including more than 4000 children and adults have shown that cefprozil is well-tolerated . The most common adverse events associated with cefprozil are gastrointestinal disturbances (i.e . diarrhea and nausea) . In two patient satisfaction surveys (pediatric and adult), cefprozil was cited for having a low incidence of side effects and was rated by children as having a pleasing taste . These data indicate that cefprozil is a practical therapeutic choice for the treatment of upper and lower respiratory tract infections.

Pediatr Infect Dis J, 1998 Aug, 17(8 Suppl), S73 - 8
Upper respiratory tract infections in family practice; Ruoff G; The causative pathogens in the majority of mild to moderate upper respiratory tract infections are Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis . Bacterial infections of the respiratory tract are often treated empirically; however, the recent increase in serious infections caused by S . pneumoniae and rising antimicrobial resistance rates have prompted experts to reevaluate the therapeutic approaches to treatment of these infections . Although amoxicillin continues to be considered a first line therapy, some situations warrant alternative therapies . Antimicrobial therapy must provide effective coverage of the potential pathogens, yet issues of compliance must also be addressed to ensure clinical success . Ease of administration, taste and the potential for adverse events are important considerations for the pediatric population . Clinical trials support the use of alternative therapies in the treatment of patients with upper respiratory tract infections.

Pediatr Infect Dis J, 1998 Aug, 17(8 Suppl), S68 - 72
Clinical perspectives on sinusitis and otitis media; Blumer J; As the leading cause of physician office visits and loss of time from school as well as the cause of significant morbidity among young children, respiratory infections impose a major burden on the health care system . The most common causative pathogens are Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis . In young children acute otitis media and sinusitis may present with relatively nonspecific symptoms such as irritability . Older children may complain of more specific problems; for example those with otitis media may complain of otalgia . Upper respiratory tract infections are typically diagnosed by signs and symptoms and treated empirically with an antimicrobial agent that offers coverage of the usual causative respiratory pathogens.

Pediatr Infect Dis J, 1998 Aug, 17(8 Suppl), S55 - 61
Microbiology of bacterial respiratory infections; Cappelletty D; The upper respiratory tract may become susceptible to bacterial infection as a result of health conditions such as allergies and viral infections, as well as the effects of smoking and airborne environmental pollutants . Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are the most common bacterial pathogens in upper and lower respiratory tract infections . Streptococcus pyogenes is the predominant bacterial pathogen in pharyngitis and tonsillitis . Bacterial pathogens adhere to mucous membranes and colonization ensues . In an otherwise healthy individual the host immune system responds to the invading bacteria resulting in edema and swelling . If antimicrobial treatment does not eradicate the invading organisms and successfully interrupt the progress of the infection, the patient may develop recurrent or chronic disease . S . pneumoniae and other pathogens once susceptible to penicillin and other antibiotics are now becoming resistant . Bacterial resistance has developed and disseminated because of the widespread use of antibiotics . Major mechanisms of bacterial resistance to antimicrobials in upper respiratory tract infections include enzymatic inhibition, membrane impermeability, alteration of target enzymes, active pumping out of antibiotic and alteration of the ribosomal target.

Pediatr Infect Dis J, 1998 Aug, 17(8 Suppl), S53 - 4
Cefprozil and respiratory tract infections in children; Pichichero ME; Respiratory tract infections are the leading cause of children's visits to physicians . Antibiotic resistance is increasing among the three most common bacterial respiratory pathogens, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, which cause acute otitis media and sinusitis . Therefore clinicians may need to reexamine their treatment strategies because these infections may cause complications . Antibiotic selection in such infections should take into account local bacterial resistance patterns, anticipated clinical efficacy against S . pneumoniae, H . influenzae and M . catarrhalis, including penicillin-resistant and beta-lactamase-producing strains, as well as the safety profile and compliance-enhancing features of the drug.

Front Biosci, 1998 Sep 01, 3, D989 - 96
Molecular and genetic analysis of iron uptake proteins in the brazilian purpuric fever clone of Haemophilus influenzae biogroup aegyptius; Smoot LM et al.; Haemophilus influenzae biogroup aegyptius (H . aegyptius) is the etiological agent of Brazilian purpuric fever (BPF), a recently described pediatric disease that is often fatal . The vascular destruction that occurs in this disease is a distinctive trait, and little is known about the mechanism(s) of the overwhelming purpura fulminans that causes the high mortality associated with this pediatric infection . Iron is an essential micronutrient for nearly all living cells, and the mechanisms used by bacteria to acquire and internalize iron are often associated with virulence . Therefore, the focus of our studies is the molecular characterization of the iron uptake system used by H . aegyptius . Specifically, we are investigating the high-affinity transferrin binding proteins in the bacterial outer membrane, components of ABC transporter systems, and a possible regulatory mechanism for the genes encoding these proteins . A detailed understanding of the molecular nature of the regulatory genetic components and proteins involved in the acquisition of iron will broaden the knowledge of the pathogenesis of the disease caused by H . aegyptius and will also lead to a better understanding of the nature of other infections that affect the vascular system.

Pediatr Infect Dis J, 1998 Aug, 17(8), 680 - 9
Microbiology of acute otitis media in Costa Rican children; Arguedas A et al.; BACKGROUND: Because of the increasing number of resistant middle ear pathogens reported from different centers worldwide, an active surveillance of the microbiology and susceptibility pattern of middle ear pathogens is required for proper antimicrobial recommendations among different regions of the world . OBJECTIVE: To study the microbiology and susceptibility pattern of middle ear pathogens obtained from Costa Rican children with acute otitis media . METHODS: Between 1992 and 1997 a diagnostic tympanocentesis was performed in 398 Costa Rican patients with acute otitis media . Middle ear fluid was obtained for culture and minimal inhibitory concentrations were determined by the E-test technique in those isolates obtained between October, 1995, and January, 1997 . RESULTS: The most common pathogens cultured were Streptococcus pneumoniae (30%), Haemophilus influenzae (14%), Staphylococcus aureus (4%) and Streptococcus pyogenes (4%) . Moraxella catarrhalis was uncommon . Beta-lactamase production was low (3.7%) among the H . influenzae isolates but frequent among the Staphylococcus aureus (57.1%) and M . catarrhalis (100%) strains . Overall 9 of 46 S . pneumoniae isolates (19.6%) exhibited decreased susceptibility to penicillin of which 8 isolates (17.4%) showed intermediate and one strain (2.2%) high level resistance . Among the penicillin-susceptible S . pneumoniae isolates, susceptibility to the following antimicrobials was: 81%, azithromycin; 89%, clarithromycin; and 100%, ceftriaxone and trimethoprim-sulfamethoxazole (TMP-SMX) . Among the penicillin-resistant S . pneumoniae isolates the percentage of susceptible strains was 89% for azithromycin, clarithromycin and ceftriaxone and 67% for TMP-SMX . CONCLUSIONS: Based on this microbiologic information the agents considered first line drugs in the treatment of acute otitis media in Costa Rica remain amoxicillin or TMP-SMX.

Immunol Cell Biol, 1998 Aug, 76(4), 323 - 31
Characteristics of the immunological response in the clearance of non-typeable Haemophilus influenzae from the lung; Foxwell AR et al.; Clearance of non-typeable Haemophilus influenzae (NTHi) from the respiratory tract was investigated, over time, in immune and non-immune rats . A triphasic pattern characterized the clearance of bacteria from the lungs . Mucosal immunization enhanced bacterial clearance from the lungs in each of the three phases compared with clearance from non-immunized animals . Total clearance of bacteria was observed from lung tissue by 12 h in immune animals and 24 h in non-immune animals . Polymorphonuclear leucocytes not only arrived earlier and initially in greater numbers, but disappeared earlier in immune animals (peaking at 8 h post-challenge), compared with non-immune animals (peaking at 12h post-challenge) . Systemically derived and locally produced NTHi-specific IgA and IgG correlated with enhanced bacterial clearance during the secondary phase . This model demonstrates that immunized animals up-regulate and resolve inflammatory responses to pulmonary infection more rapidly than the non-immunized controls.

Bratisl Lek Listy, 1998 Jun, 99(6), 291 - 5
{Perioperative care by internists in splenectomy}; Remkova A; Splenectomy (SE) is one of the surgical interventions requiring an increased internal care . The removal of the spleen which is an organ with an exceptional function can lead to complications even in people who are healthy in all other respects . The complications in coincidence with SE can arise early (up to 30 days after surgery) or later . Early complications can involve infections of the respiratory tract (especially bronchopneumonia), or subphrenic abscess . Thromboembolic complications occur not only in peri-operational period, but also in several weeks or months after SE . A severe complication resides in disseminated intravascular blood coagulation . Late complications represent a lifelong danger for asplenic patients . They include the fulminant sepsis, known as so-called OPSI syndrome (overwhelming postsplenectomy infection) . The mortality rate in coincidence with the latter is very high despite intensive antibiotic therapy . The risk is especially high in children, in immuno-deficient states and immunosuppressive therapy . 60% of patients develop OPSI during the first two years, out of whom one third is afflicted in the first half of the year following SE . In more than 30% of patients OPSI manifests itself minimally 5 years later . The prevention of infection in coincidence with SE is performed by means of immunization, antibiotic prophylaxis and via education of patients . Immunization includes the administration of a polyvalent pneumococcus vaccine, in children it includes also the vaccine against Haemophilus inluenzae and Neisseria meningitidis . The appropriate antibiotic prophylaxis is represented especially by penicillin, amoxicillin, or amoxicillin with clavulanic acid . The children or other patients with disturbed immunity functions are administered with antibiotics in low doses per os for a long period . Antibiotics in the therapy of OPSI are administered in full doses together with immunoglobulin, both are applied intravenously . A specific approach is required in patients with autoimmune thrombocytopenia, in whom the increase in the number of thrombocytes prior to operation can be achieved by high intravenous doses of corticoids or immunoglobulin G . In this case, unless explicitly necessary, the transfusion of thrombocytes should not be performed prior to SE . The antithrombotic therapy is appropriate in patients at high risk of post-surgical thrombosis (e.g . hereditary haemolytic anaemias, myeloproliferative diseases, SE in coincidence with polytraumatism.

J Bacteriol, 1998 Sep, 180(17), 4693 - 703
Evolution of the major pilus gene cluster of Haemophilus influenzae; Mhlanga-Mutangadura T et al.; Haemophilus influenzae is a ubiquitous colonizer of the human respiratory tract and causes diseases ranging from otitis media to meningitis . Many H . influenzae isolates express pili (fimbriae), which mediate adherence to epithelial cells and facilitate colonization . The pilus gene (hif) cluster of H . influenzae type b maps between purE and pepN and resembles a pathogenicity island: it is present in invasive strains, absent from the nonpathogenic Rd strain, and flanked by direct repeats of sequence at the insertion site . To investigate the evolution and role in pathogenesis of the hif cluster, we compared the purE-pepN regions of various H . influenzae laboratory strains and clinical isolates . Unlike Rd, most strains had an insert at this site, which usually was the only chromosomal locus of hif DNA . The inserts are diverse in length and organization: among 20 strains, nine different arrangements were found . Several nontypeable isolates lack hif genes but have two conserved open reading frames (hicA and hicB) upstream of purE; their inferred products are small proteins with no data bank homologs . Other isolates have hif genes but lack hic DNA or have combinations of hif and hic genes . By comparing these arrangements, we have reconstructed a hypothetical ancestral genotype, the extended hif cluster . The hif region of INT1, an invasive nontypeable isolate, resembles the hypothetical ancestor . We propose that a progenitor strain acquired the extended cluster by horizontal transfer and that other variants arose as deletions . The structure of the hif cluster may correlate with colonization site or pathogenicity.

J Bacteriol, 1998 Sep, 180(17), 4401 - 5
A 3',5' cyclic AMP (cAMP) phosphodiesterase modulates cAMP levels and optimizes competence in Haemophilus influenzae Rd; Macfadyen LP et al.; Changes in intracellular 3',5' cyclic AMP (cAMP) concentration regulate the development of natural competence in Haemophilus influenzae . In Escherichia coli, cAMP levels are modulated by a cAMP phosphodiesterase encoded by the cpdA gene . We have used several approaches to demonstrate that the homologous icc gene of H . influenzae encodes a functional cAMP phosphodiesterase and that this gene limits intracellular cAMP and thereby influences competence and other cAMP-dependent processes . In E . coli, expression of cloned icc reduced both cAMP-dependent sugar fermentation and beta-galactosidase expression, as has been shown for cpdA . In H . influenzae, an icc null mutation increased cAMP-dependent sugar fermentation and competence development in strains where these processes are limited by mutations reducing cAMP synthesis . When endogenous production of cAMP was eliminated by a cya mutation, an icc strain was 10,000-fold more sensitive to exogenous cAMP than an icc+ strain . The icc strain showed moderately elevated competence under noninducing conditions, as expected, but had subnormal competence increases at onset of stationary phase in rich medium, and on transfer to a nutrient-limited medium, suggesting that excessive cAMP may interfere with induction . Consistent with this finding, a cya strain cultured in 1 mM cAMP failed to develop maximal competence on transfer to inducing conditions . Thus, by limiting cAMP levels, the H . influenzae cAMP phosphodiesterase may coordinate its responses to nutritional stress, ensuring optimal competence development.

J Chemother, 1998 Aug, 10(4), 276 - 9
A comparison of the activity of ciprofloxacin and levofloxacin with other agents against respiratory tract pathogens; Wise R et al.; In a study involving 15 UK hospitals, sequential respiratory tract isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were studied . The susceptibility of these strains to two fluoroquinolones, ciprofloxacin and levofloxacin were compared to those of currently used macrolides and beta-lactams . The activity of ciprofloxacin and levofloxacin against S . pneumoniae was not statistically significantly different (geometric mean MIC 0.978 and 0.95 mg/L respectively) . Beta-lactam resistance did not affect fluoroquinolone susceptibility . H . influenzae and M . catarrhalis were highly susceptible to both fluoroquinolones.

Electrophoresis, 1998 Jul, 19(10), 1819 - 27
Reference map of the low molecular mass proteins of Haemophilus influenzae; Fountoulakis M et al.; Analysis of the proteome of Haemophilus influenzae by two-dimensional polyacrylamide gel electrophoresis on conventional Tris-glycine gels does not usually result in efficient separation of the proteins in the 5-20 kDa range, which are mainly accumulated in the lower acidic and basic regions . In order to improve the separation of the low molecular mass proteins, we used homogeneous Tricine gels of two urea concentrations in the second-dimensional separation . The Tricine gel systems allowed the efficient and reproducible separation of the proteins of the microorganism with masses between 5 and 20 kDa, however, no proteins with masses below 5 kDa could be visualized . Approximately 80 proteins migrating in the 5-25 kDa region were identified by matrix assisted laser desorption/ionization - mass spectrometry, of which 40 identified for the first time . The digestion of the low mass proteins often produced only few peptides, which were insufficient for confident identification by mass spectrometry . Therefore, the identification was occasionally achieved by a sequential digestion with two proteases, trypsin or endoproteinase Lys-C as first and carboxypeptidase P as second enzyme . The gel system described may be useful for the efficient separation of low molecular mass proteins from other organisms to construct standard maps.

Int J Antimicrob Agents, 1998 May, 10(2), 127 - 33
The Nearchus project: antibiotic susceptibility of respiratory pathogens and clinical outcome in lower respiratory tract infections at 27 centres in the UK; Gruneberg RN et al.; Community-acquired respiratory infections are usually treated empirically by the primary care physician . Increasing antibiotic resistance, for example, in pneumococci, prompted a UK survey of antibiotic susceptibility of three major lower respiratory tract pathogens, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis . Each of 27 centres was asked to collect up to 100 isolates of the three species and submit them for confirmation of identity and for susceptibility testing to a central laboratory . In addition, general practitioners were asked for demographic details on the patient, their treatment and the clinical outcome . Of 1689 viable pathogens collected, there were 1078 (64%) strains of H . influenzae, 258 (15%) of M . catarrhalis and 353 (21%) of S . pneumoniae . Production of beta-lactamase was detected in 163 (15%) of 1078 isolates of H . influenzae and in 243 (94%) isolates of M . catarrhalis . For S . pneumoniae, moderate resistance to penicillin (MIC 0.12-1 mg/l) was found in 12 (3.4%) isolates and high level resistance (MIC > or = 2 mg/l) in 13 (3.7%) isolates . The most common individual treatments were amoxycillin, amoxycillin/clavulanate (amoxyclav) , and erythromycin . Complete or partial clinical resolution was achieved in 88% of 809 patients infected with H . influenzae, 83% of 197 infected with M . catarrhalis and 90% of 255 infected with S . pneumoniae.

Gene, 1998 Jul 30, 215(2), 381 - 8
Glycerol-3-phosphate transport in Haemophilus influenzae: cloning, sequencing, and transcription analysis of the glpT gene; Song XM et al.; The presence of a functional glpT gene in Haemophilus influenzae could be questioned, since there is only what appears to be a truncated glpT (HI0686, 143 nt in the 5'-end) available in the H . influenzae Rd genome database (Fleischmann et al . , 1995) . For cloning of the glpT gene from H . influenzae type b strain Eagan, an isogenic glpT, rec-1 double mutant and a selective medium for detection of the glpT mutant strains were constructed . The recombinant plasmid carrying glpT was able to complement the isogenic glpT mutant to wild-type levels of G3P uptake and permitted growth on a selective medium with G3P as a major carbon source . The nucleotide sequences of the glpT gene were determined both directly from PCR products and from the cloned DNA insert of strain Eagan . An identical 1440 bp open reading frame with 480 deduced amino acids, highly homologous to other bacterial G3P permeases, was identified . A Northern blot analysis showed that the glpT genes in both Eagan and Rd strains were transcribed on a RNA of approximately 1.4 kb in size . Thus, it is likely that HI0686 sequence originates from a mutated glpT clone in Escherichia coli.

Biochim Biophys Acta, 1998 Jul 30, 1399(1), 88 - 92
Discovery of the tail tube gene of bacteriophage Mu and sequence analysis of the sheath and tube genes; Takeda S et al.; The nucleotide sequence was determined for 2.75 kbp of phage Mu DNA encoding the contractile tail sheath protein L . N-terminal sequence analysis of Mu tail tube and sheath proteins identified the open reading frame just downstream of gene L as the tube gene . This clustering and order of the sheath and tube genes appear to be common among the myoviridae . Database homology searches revealed high similarity between the Mu sheath and tube proteins and two proteins in a Haemophilus influenzae Mu-like prophage, suggesting that they are the sheath and tube proteins of that prophage.

Vaccine, 1998 Oct, 16(17), 1668 - 74
Repeated administration of whole-cell and acellular pertussis vaccines affects haemodynamics and autonomic responsiveness; van Amsterdam JG et al.; Rats were treated in a repetitive way one to four times with either pertussis toxin, combined Diphtheria-Tetanus-Poliomyelitis-Pertussis vaccine (DTP-IPV vaccine, which includes inactivated polio virus and whole-cell pertussis), DT-IPV vaccine (lacking the whole-cell pertussis component) or acellular pertussis (aP) vaccine or Haemophilus influenzae type b vaccine . Baseline diastolic blood pressure, baseline heart rate and adrenergic and cholinergic responses were evaluated 4 days after last treatment . Pertussis toxin decreased baseline diastolic blood pressure (28-43%) and increased baseline heart rate (28-40%) . Adrenergic and cholinergic response were inhibited by 65-75% and 70-78% . Multiple treatments were grossly as effective as single treatment . Similar results were obtained with DTP-IPV, while DT-IPV did not affect any of the four responses measured . Acellular pertussis vaccine did not affect baseline diastolic blood pressure, but significantly increased baseline heart rate (14%) and inhibited the adrenergic (19-23%) and cholinergic response (39-50%) . This indicates that the acellular vaccine tested contains pharmacologically active pertussis toxin . As the effects were less pronounced compared to DTP-IPV, it is concluded that acellular pertussis retains less residual toxicological effects than whole-cell pertussis vaccine and may therefore be a safer vaccine . The observed effects on haemodynamics and autonomic control seem to be specific for pertussis toxin and pertussis-related vaccines as Haemophilus influenzae type b vaccine is in this respect virtually inactive.

Am Fam Physician, 1998 Aug, 58(2), 443 - 50
A different look at corticosteroids; Zoorob RJ et al.; Systemic corticosteroids have been used in the treatment of numerous medical conditions for approximately 50 years . Short-acting products such as hydrocortisone are the least potent . Prednisone and methylprednisolone, which are intermediate-acting products, are four to five times more potent than hydrocortisone . Dexamethasone is a long-acting, systemic corticosteroid; its potency is about 25 times greater than the short-acting products . Corticosteroids reduce the need for hospitalization in patients with croup and decrease morbidity and the incidence of respiratory failure in the treatment of patients with AIDS who have Pneumocystis carinii pneumonia . Other often overlooked indications for corticosteroids are the treatment of hyperthyroid states, including thyroid storm, subacute thyroiditis and ophthalmopathy of Graves' disease . Systemic steroids can be used as adjuvant analgesics in the treatment of neuropathic and cancer-related pain . They may also decrease mortality in patients with severe alcoholic hepatitis and concomitant encephalopathy . Corticosteroids can reduce complications in patients with meningitis caused by Haemophilus influenzae or Mycobacterium tuberculosis.

Rev Med Liege, 1998 Jun, 53(6), 327 - 8
{Neonatal type 1 pneumococcal meningitis and maternal septicemia}; Verghote M et al.; The most common organisms in neonatal meningitis are group B streptococcus and Gram negative enteric bacteriae . Although Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae are the most frequent causes of meningitis in infancy and childhood, they are uncommon in newborns . We report one case of neonatal meningitis and maternal septicemia.

Acta Vet Hung, 1998, 46(4), 405 - 14
Occurrence of some viruses and bacteria involved in respiratory diseases of ruminants in Hungary; Rusvai M et al.; Serological surveys, virological and bacteriological investigations were carried out on large populations of lambs and calves kept in intensive fattening units on Hungarian large-scale farms, in order to study the occurrence of viruses and bacteria involved in the respiratory disease complex . The investigations were carried out in stocks where 5-20% of the young animals succumbed to acute or chronic pneumonia every year . Serological surveys revealed that seropositivity to bovine adenovirus type 2 (BAV-2) and parainfluenza type 3 (PI-3) were the most widespread viral infections both in cattle and sheep (BAV-2: 56% and 88%, PI-3: 76% and 41%, respectively) . Antibodies against infectious bovine rhinotracheitis virus (BHV-1) were also found in a high proportion (45%) of sera of 3-8 month old calves, while in 2-6 month old lambs ovine adenovirus 1 (OAV-1) was the third most frequent virus (22%) . Bacteriological investigations demonstrated secondary infections caused by different Pasteurella haemolytica and Pasteurella multocida serotypes in most cases . In cattle herds P . multocida A proved to be the predominant bacterium: it was isolated in each herd examined, while P . haemolytica A1 strains were isolated in 7 and Haemophilus somnus in 2 out of 13 herds . In sheep flocks P . haemolytica was the most frequent species isolated, 10 serotypes were cultured from pneumonic sheep but serotypes A2, A1 and A8 were the dominant ones.

Rev Inst Med Trop Sao Paulo, 1998 Jan-Feb, 40(1), 7 - 9
Streptococcus pneumoniae and Haemophilus influenzae as etiological agents of conjunctivitis outbreaks in the region of Ribeirão Preto, SP, Brazil; Medeiros MI et al.; In the study of conjunctivitis outbreaks occurring from September 1994 to September 1996 in the region of Ribeirao Preto, conjunctival exudates of 92 patients were cultivated in Instituto Adolfo Lutz Laboratory I, Ribeirao Preto . Most cases occurred in the age range 2-7 years . The etiological agents which were most frequently isolated from the analyzed cases were: Streptococcus pneumoniae and Haemophilus influenzae, in 40.22% and 21.74%, respectively . 51.35% of the S . pneumoniae isolated strains were not typable . The oxacillin-resistant S . pneumoniae strains were submitted to the minimum inhibitory concentration test (MIC) and three of them presented intermediate resistance, whereas only one was highly resistant to penicillin.

Infect Immun, 1998 Sep, 66(9), 4511 - 6
Binding of heme-hemopexin complexes by soluble HxuA protein allows utilization of this complexed heme by Haemophilus influenzae; Cope LD et al.; Utilization of heme-hemopexin as a source of heme by Haemophilus influenzae type b is dependent on expression by this bacterium of the 100-kDa HxuA protein, which is both present on the bacterial cell surface and released into the culture supernatant (L . D . Cope, R . Yogev, U . Muller-Eberhard, and E . J . Hansen, J . Bacteriol . 177:2644-2653, 1995) . Radioimmunoprecipitation analysis showed that the soluble HxuA protein present in H . influenzae type b culture supernatant bound heme-hemopexin complexes in solution . An isogenic H . influenzae type b hxuA mutant was unable to utilize soluble heme-hemopexin complexes for growth in vitro unless soluble HxuA protein was provided exogenously . Soluble HxuA protein secreted by a nontypeable H . influenzae strain also allowed growth of this H . influenzae type b hxuA mutant . These results indicated that the heme present in heme-hemopexin complexes is rendered accessible to H . influenzae when these complexes are bound by the soluble HxuA protein.

Infect Immun, 1998 Sep, 66(9), 4290 - 8
Involvement of the Haemophilus ducreyi gmhA gene product in lipooligosaccharide expression and virulence; Bauer BA et al.; The lipooligosaccharide (LOS) present in the outer membrane of Haemophilus ducreyi is likely a virulence factor for this sexually transmitted pathogen . An open reading frame in H . ducreyi 35000 was found to encode a predicted protein that had 87% identity with the protein product of the gmhA (isn) gene of Haemophilus influenzae . In H . influenzae type b, inactivation of the gmhA gene caused the synthesis of a significantly truncated LOS which possessed only lipid A and a single 2-keto-3-deoxyoctulosonic acid molecule (A . Preston, D . J . Maskell, A . Johnson, and E . R . Moxon, J . Bacteriol . 178:396-402, 1996) . The H . ducreyi gmhA gene was able to complement a gmhA-deficient Escherichia coli strain, a result which confirmed the identity of this gene . When the gmhA gene of H . ducreyi was inactivated by insertion of a cat cartridge, the resultant H . ducreyi gmhA mutant, 35000.252, expressed a LOS that migrated much faster than wild-type LOS in sodium dodecyl sulfate-polyacrylamide gel electrophoresis . When the wild-type H . ducreyi strain and its isogenic gmhA mutant were used in the temperature-dependent rabbit model for dermal lesion production by H . ducreyi, the gmhA mutant was found to be substantially less virulent than the wild-type parent strain . The H . ducreyi gmhA gene was amplified by PCR from the H . ducreyi chromosome and cloned into the pLS88 vector . When the H . ducreyi gmhA gene was present in trans in gmhA mutant 35000.252, expression of the gmhA gene product restored the virulence of this mutant to wild-type levels . These results indicate that the gmhA gene product of H . ducreyi is essential for the expression of wild-type LOS by this pathogen.

Infect Immun, 1998 Sep, 66(9), 4263 - 7
The phosphorylcholine epitope undergoes phase variation on a 43-kilodalton protein in Pseudomonas aeruginosa and on pili of Neisseria meningitidis and Neisseria gonorrhoeae; Weiser JN et al.; Phosphorylcholine (ChoP) is a component of the teichoic acids of Streptococcus pneumoniae and has been recently identified on the lipopolysaccharide of Haemophilus influenzae, also a major pathogen of the human respiratory tract . Other gram-negative pathogens that frequently infect the human respiratory tract were surveyed for the presence of the ChoP epitope as indicated by binding to monoclonal antibodies (MAbs) recognizing this structure . The ChoP epitope was found on a 43-kDa protein on all clinical isolates of Pseudomonas aeruginosa examined and on several class I and II pili of Neisseria meningitidis . The specificity of the anti-ChoP MAb was demonstrated by the inhibition of binding in the presence of ChoP but not structural analogs . As in the case of H . influenzae, the expression of this epitope was phase variable on these species . In P . aeruginosa, this epitope was expressed at detectable levels only at lower growth temperatures . Expression of the ChoP epitope on piliated neisseriae displayed phase variation, both linked to pilus expression and independently of fully piliated bacteria.

Infect Immun, 1998 Sep, 66(9), 4254 - 62
Cloning and characterization of tdhA, a locus encoding a TonB-dependent heme receptor from Haemophilus ducreyi; Thomas CE et al.; Haemophilus ducreyi is unable to synthesize heme and must acquire it from its only known host, humans . We cloned and sequenced a gene encoding an outer membrane receptor for heme . It was designated tdhA (for TonB-dependent heme receptor A) since it was related by sequence homology to the family of TonB-dependent receptors . TdhA was strikingly similar to open reading frame HI0113 from the genome of Haemophilus influenzae Rd and also shared homology with five other heme receptors, including HxuC, HemR, HmuR, ChuA, and ShuA, from gram-negative bacteria . An Escherichia coli hemA tonB mutant strongly expressing H . ducreyi tdhA grew on low levels of heme as a source of heme only when an intact H . ducreyi Ton system plasmid was present, formally demonstrating functional TonB dependence . tdhA was expressed poorly in vitro by H . ducreyi and only under conditions of heme limitation . A survey of H . ducreyi revealed that all tested strains but one synthesized small amounts of TdhA in vitro under heme-limiting conditions . Surprisingly, an isogenic mutant of tdhA as well as its parent, 35000, both required the same high levels of heme for growth (50 microgram/ml {77 microM} on agar medium) . This result, together with previous findings, suggests that in vitro, the uptake of heme by H . ducreyi is mediated by a TonB- and TdhA-independent mechanism, possibly diffusion.

Microb Pathog, 1998 Aug, 25(2), 67 - 75
Antibodies specific to surface antigens are not effective in complement-mediated killing of Haemophilus ducreyi; Frisk A et al.; The bactericidal activity of serum is an important primary host defence against gram-negative bacteria . Little is known regarding such antibodies that are specific to outer membrane (OM) antigens as pili and lipooligosaccharides (LOS) in the bactericidal killing of Haemophilus ducreyi . Presence of serum antibodies with specificity to a 430 kDa protein (polymer of the 24 kDa protein, named fine-tangled pili) and LOS in serum from chancroid patients and healthy individuals were investigated by ELISA . Using a bactericidal assay, we investigated the role of human and rabbit antibodies with the aforementioned specificity . Accessibility of LOS and of OM antigens, as well as the deposition of components of the complement (C) system on the surface of the bacteria, was further investigated by whole-cell ELISA and immunoelectron microscopy . Immunoglobulin G (IgG) antibodies specific to the 430 kDa polymer and to LOS were demonstrated in the majority of sera from chancroid patients and healthy individuals . However, sera from chancroid patients did not significantly enhance the C-mediated killing of H . ducreyi compared with normal human serum (NHS) . Similar results were demonstrated using rabbit sera to whole bacteria, specific to the 430 kDa protein and LOS of H . ducreyi . However, using the same assay noncapsulatedH . influenzae was totally killed, as were H . influenzae type b in presence of specific antibodies . This suggests a limited effectiveness of antibodies specific to surface antigens in C-mediated killing of H . ducreyi . LOS was detectable on the surface of H . ducreyi with a specific monoclonal antibody in white-cell ELISA . However, a significant enhancement of LOS detection was demonstrated on washed bacteria . OM antigens of 26, 40, 45 kDa and the major outer membrane protein (MOMP) of 43 kDa were not detectable on the surface of nonwashed and washed bacteria by specific monoclonal antibodies, indicating a lack of accessibility of these antigens on the bacterial surface . However, the C6 to C9 components of C were detected on the bacterial surface, suggesting capacity of forming the membrane attack complex . Altogether, these findings imply that antibodies specific to surface antigens, such as the 430 kDa protein and LOS, are not capable of enhancing killing of bacteria . The demonstrated relative resistance is probably due not to a lack of deposition of the membrane attack complex components, but rather to a blocking of LOS accessibility and OM proteins as potential targets of bactericidal antibodies and C action .

FEMS Microbiol Lett, 1998 Aug 1, 165(1), 71 - 7
Characterization of a fourth lipoprotein from Pasteurella haemolytica A1 and its homology to the OmpA family of outer membrane proteins; Nardini PM et al.; A fourth lipoprotein gene from Pasteurella haemolytica A1 was cloned and characterized . The plpD gene encodes a 31-kDa lipoprotein (Plp4) which could be recognized in Western immunoblot by sera from calves immunized with the culture supernatant vaccine Presponse . This suggests that Plp4 is one of the immunogenic molecules in the P . haemolytica A1 culture supernatant . The lipoprotein nature of Plp4 was confirmed by labelling with {3H}palmitate and inhibition of leader peptide cleavage with globomycin . A homology search with databanks showed extensive homology between Plp4 and a 31-kDa antigen from Haemophilus somnus and a 19.2-kDa antigen from Neisseria meningitidis . Additional homology of the distal half of Plp4 was identified with a number of bacterial outer membrane proteins belonging to the OmpA family . Plp4 appears to be a novel type of outer membrane protein that contains motifs typical of OmpA but which is also lipid modified.

Vaccine, 1998 Oct, 16(16), 1582 - 8
Acute respiratory infections (ARI) in children: prospects for prevention; Monto AS et al.; Acute respiratory infections (ARI) are a major cause of morbidity in children worldwide, and are estimated to cause four million deaths per year, mainly in the developing world . In those countries, bacterial infection with high case fatality is common, apparently following a primary viral infection . The case management strategy has had success in controlling severe outcomes . However, its dependence on the use of antibiotics and the advantage of primary prevention support the need for vaccines . Vaccines against viruses such as respiratory syncytial and parainfluenza would prevent what is often the initial infection and vaccines against Haemophilus influenzae and S . pneumoniae the major bacterial causes of mortality . Maternal immunization may have special relevance in developing countries where protection early in life is required . The development of combination vaccines would also be especially useful, since contacts with the medical system are often difficult . The introduction and use of new vaccines in those regions will require demonstration of cost effectiveness and acceptance by policy makers.

Vaccine, 1998 Aug-Sep, 16(14-15), 1391 - 5
Potential and limitations of polysaccharide vaccines in infancy; Cadoz M; Of infections caused by encapsulated bacteria, those due to Haemophilus influenzae b (Hib) are among the most restricted to infancy and require very early immunisation . Hib capsular polysaccharide (CPS) has the most typical T-cell independent profile . The absence of efficacy of this vaccine in infants triggered development of conjugate vaccines which are so effective that there is now no room for plain polysaccharide Hib vaccines . Pneumococcal infections pose similar problems to Hib, but are more complex . The immunogenicity of the different pneumococcal serotypes varies considerably in infancy . Although the current CPS vaccine provides limited protection in infancy, the burden of pneumococcal infection is so high that its use could be reconsidered should conjugate vaccines be available later than expected . Meningococcal infections are less a specific problem for infants . Again, serogroup immunogenicity varies widely . Group B meningococcal CPS is not immunogenic even in adults, Group C behaves as Hib CPS, whereas Group A is immunogenic as early as 6 months of age . Group A CPS may prove of interest for an infant vaccine, especially in epidemic situations . Typhoid fever is uncommon in infancy; Vi CPS is poorly immunogenic in infancy and is, therefore, of limited interest for use as an infant vaccine.

Drugs, 1998 Aug, 56(2), 273 - 97
Azithromycin . A review of its use in paediatric infectious diseases; Langtry HD et al.; Azithromycin is an azalide antimicrobial agent active in vitro against major pathogens responsible for infections of the respiratory tract, skin and soft tissues in children . Pathogens that are generally susceptible to azithromycin include Haemophilus influenzae (including ampicillin-resistant strains), Moraxella catarrhalis, Chlamydia pneumoniae, Chlamydia trachomatis, Mycoplasma pneumoniae, Legionella spp., Streptococcus pyogenes and Streptococcus agalactiae . Azithromycin is also generally active against erythromycin- and penicillin-susceptible Streptococcus pneumoniae and methicillin-susceptible Staphylococcus aureus . Azithromycin is administered once daily, achieves clinically relevant concentrations at sites of infection, is slowly eliminated from the body and has few drug interactions . In children, azithromycin is usually given as either a 3-day course of 10 mg/kg/day or a 5-day course with 10 mg/kg on the first day, followed by 5 mg/kg/day for a further 4 days . These standard regimens were as effective as amoxicillin/clavulanic acid, clarithromycin, cefaclor and amoxicillin in the treatment of children with otitis media . Azithromycin was also as effective as either phenoxymethylpenicillin (penicillin V), erythromycin, clarithromycin or cefaclor against streptococcal pharyngitis or tonsillitis in children, but appears to result in more recurrence of infection than phenoxymethylpenicillin in this indication, necessitating a dosage of 12 mg/kg/day for 5 days . Community-acquired pneumonia, bronchitis and other respiratory tract infections in children responded as well to azithromycin as to amoxicillin/clavulanic acid, cefaclor, erythromycin or josamycin . Azithromycin was similar or superior to ceftibuten in mixed general practice populations of patients . However, symptoms of lower respiratory tract infections resolved more rapidly with azithromycin than with erythromycin, josamycin or cefaclor . Skin and soft tissue infections responded as well to azithromycin as to cefaclor, dicloxacillin or flucloxacillin, and oral azithromycin was as effective as ocular tetracycline in treating trachoma . Although not as well tolerated as phenoxymethylpenicillin in the treatment of streptococcal pharyngitis, azithromycin is at least as well tolerated as most other agents used to treat respiratory tract and other infections in children and was better tolerated than amoxicillin/clavulanic acid . Adverse events that do occur are mostly gastrointestinal and tend to be mild to moderate in severity . CONCLUSIONS: Azithromycin is an effective and well tolerated alternative to first-line agents in the treatment of respiratory tract, skin and soft tissue infections in children, offerring the convenience of a short, once-daily regimen.

Microb Pathog, 1998 Jul, 25(1), 11 - 21
Omp85 proteins of Neisseria gonorrhoeae and Neisseria meningitidis are similar to Haemophilus influenzae D-15-Ag and Pasteurella multocida Oma87; Manning DS et al.; The genes encoding homologous 85 kDa outer membrane proteins of Neisseria gonorrhoeae and Neisseria meningitidis have been cloned and sequenced . The gonococcal gene, omp85, was identified by screening a genomic library with an antiserum raised against purified gonococcal outer membranes . The gene encoded a 792 amino acid protein, Omp85, having a typical signal peptide and a carboxyl-terminal phenylalanine characteristic of outer membrane proteins . The amino acid sequence was similar to that of the D15 protective surface antigen (D-15-Ag) of Haemophilus influenzae, and the Oma87 of Pasteurella multocida . Southern analysis demonstrated that omp85 was present as a single copy in N . gonorrhoeae and N . meningitidis . PCR amplification was used to obtain a clone of the N . meningitidis omp85 homologue . Sequence analysis revealed that the N . meningitidis Omp85 was 95% identical to the N . gonorrhoeae Omp85.

J Acquir Immune Defic Syndr Hum Retrovirol, 1998 Aug 1, 18(4), 372 - 9
HIV-1 subtype E incidence and sexually transmitted diseases in a cohort of military conscripts in northern Thailand; Nopkesorn T et al.; OBJECTIVES: To determine the rate of and risk factors for HIV-1 seroconversion and describe sexually transmitted disease (STD) prevalence rates for young men in northern Thailand . METHODS: Data were collected from self-administered questionnaires and serologic testing at enrollment in a prospective study in 1991 and at follow-up after 6, 17, and 23 months on a cohort of 1115 men selected by lottery for military conscription . RESULTS: A total of 14 men seroconverted to HIV-1 envelope subtype E . The overall HIV-1 incidence rate was 1.1 (95% confidence interval {CI}, 0.6-1.8) per 100 person-years (PY) of follow-up . However, the rate was 2.0/100 PY for conscripts from the upper northern subregion of Thailand compared with 0.5/100 PY from other regions (adjusted rate ratio {RR} = 2.69; 95% CI, 0.8-12.2) . On multivariate analyses, the behavioral factors associated with HIV-1 seroconversion were frequency of sex with female sex workers (FSWs; p = .04), receptive anal sex (adjusted RR = 6.73; 95% CI, 1.8-21.7), and large amount of alcohol consumption (adjusted RR = 3.12; 95% CI, 1.0-10.9) . Genital ulceration was the STD most strongly associated with seroconversion . The prevalence of serologic reactivity to syphilis, Haemophilus ducreyi, and herpes simplex virus type 2 increased with greater frequency of sex with FSWs and was generally higher for men from the upper north . CONCLUSION: Young men in northern Thailand are at high risk for HIV-1, primarily through sex with FSWs; and other STDs are highly associated with HIV-1 incidence . As HIV-1 infection extends into the general population, intervention programs are needed to address the problem of sexual transmission apart from commercial sex venuesPIP: Findings are presented from a prospective study conducted to determine the rate of and risk factors for HIV-1 seroconversion, and to describe sexually transmitted diseases (STD) prevalence rates for young men in northern Thailand . Study findings are based upon data collected from self-administered questionnaires and serologic testing at enrollment in 1991 and at follow-up after 6, 17, and 23 months on a cohort of 1115 young men chosen by lottery for military conscription . Men in Thailand are generally eligible for conscription in the year of their 21st birthday . 6.9% of the men were HIV-1 seropositive at enrollment; 15.3% of men from the upper northern region compared with 2.5% of men from elsewhere . 14 subjects seroconverted to HIV-1 envelope subtype E over the course of the study . The overall HIV-1 incidence rate was 1.1/100 person-years (PY) of follow-up . However, the rate was 2.0/100 PY for conscripts from the upper northern subregion of Thailand compared with 0.5/100 PY from other regions . Multivariate analyses found frequent sex with female prostitutes, receptive anal sex, and high levels of alcohol consumption to be positively associated with HIV-1 seroconversion . Genital ulceration was the STD most strongly associated with seroconversion . The prevalence of serologic reactivity to syphilis, Haemophilus ducreyi, and herpes simplex virus type 2 increased with greater frequency of sex with female prostitutes, and was generally higher for men from the upper north .

Mol Microbiol, 1998 Jul, 29(1), 247 - 59
MglA and MglB are required for the intramacrophage growth of Francisella novicida; Baron GS et al.; Francisella novicida is a facultative intracellular pathogen capable of growing in macrophages . A spontaneous mutant of F . novicida defective for growth in macrophages was isolated on LB media containing the chromogenic phosphatase substrate 5-bromo-4-chloro-3-indolyl phosphate (X-p) and designated GB2 . Using an in cis complementation strategy, four strains were isolated that are restored for growth in macrophages . A locus isolated from one of these strains complements GB2 for both the intracellular growth defect and the colony morphology on LB (X-p) media . The locus consists of an apparent operon of two genes, designated mgIAB, for Macrophage Growth Locus . Both mglA and mglB transposon insertion mutants are defective for intracellular growth and have a phenotype similar to GB2 or LB (X-p) media . Sequencing on mglA cloned from GB2 identified a missense mutation, providing evidence that both mglA and mglB are required for the intramacrophage growth of F . novicida . mglB expression in GB2 was confirmed using antiserum against recombinant MglB . Cell fractionation studies revealed several differences in the protein profiles of mgI mutants compared with wild-type F . novicida . The deduced amino acid sequences of mglA and mglB show similarity to the SspA and SspB proteins of Escherichia coli and Haemophilus spp . In E . coli, SspA and/or SspB influence the levels of multiple proteins under conditions of nutritional stress, and SspA can associate with the RNA polymerase holoenzyme . Taken together, these observations suggest that in Francisella MglA and MglB may affect the expression of genes whose products contribute to survival and growth within macrophages.

Arch Pediatr Adolesc Med, 1998 Aug, 152(8), 745 - 8
Population-based study of the adequacy of well-child care services: a rural county's report card; Gadomski AM et al.; OBJECTIVE: To determine the adequacy of well-child care services using a population-based study . DESIGN: The medical records of all county providers and the immunization records at the local health department were reviewed . A county birth cohort, identified using electronic birth certificates, was compared with those who migrated into the area (hereafter, in-migrants) . SETTING: All primary care sites (private, network, etc) in a rural county . PATIENTS: Two-year-old children born between May 31, 1993, and May 30, 1994 . MAIN OUTCOME MEASURES: Immunization rates and preventive screenings . RESULTS: A total of 674 medical records were reviewed . Of these, 377 (56%) belonged to a county birth cohort and 297 (44%) were in-migrants . Medical records of 64% of the birth cohort were reviewed . Among all 2-year-olds, 80% received 4 doses of diphtheria and tetanus toxoids and pertussis vaccine; 89%, 3 doses of Haemophilus influenzae type b (Hib); 75%, 4 doses of Hib; 77%, 3 doses of hepatitis B vaccine; 85%, measles-mumps-rubella vaccine; 85%, 3 doses of oral poliovirus vaccine; 17%, varicella live virus vaccine (Varivax) . The 4:3:1 rate was 75% at age 2 years . Sixty-eight percent had had 1 hematocrit, 74% had 1 lead screening test, and 43% had 2 lead screening tests . A total of 64% had had 6 well-child visits and 30% had had 9 . The mean number of weights and heights measured was 4.8 and 4.5, respectively, at age 1 year and 7.3 and 6.8, respectively, at age 2 years . The birth cohort had notably higher rates of documented immunization and preventive screening than in-migrants . CONCLUSIONS: This study demonstrated immunization coverage at or below the national average, and well-child care service provisions below American Academy of Pediatrics standards at a county level . This study enabled individual primary care sites to assess their well-child care provision and provided a useful baseline for targeting the improvement of well-child care services in the county.

Microbiology, 1998 Jul, 144 ( Pt 7), 1807 - 13
An aminopeptidase nutritionally important to Fusobacterium nucleatum; Rogers AH et al.; The properties of an aminopeptidase (AP) from Fusobacterium nucleatum were studied in view of the fact that this organism, along with other Gram-negative anaerobes involved in periodontal diseases, survives in the subgingival environment by obtaining energy via the fermentation of a small number of peptide-derived amino acids . The AP was found to be cell-associated and was isolated from disrupted chemostat-grown cells . It was purified by (NH4)2SO4 fractionation, two column chromatographic steps and IEF . The enzyme was found to have a molecular mass of 54 kDa, a pI of 5.1, a pH optimum between 7.5 and 8.0 and, using Leu-Ala as substrate, it gave K(m) and Vmax values of 0.66 mM and 0.12 mumol min-1 mg-1, respectively . No complete homology was found between the N-terminal sequence of the first 20 amino acids (MDXKXYVDLKERFLRYVKFN...) and any other published sequence, but residues 8-20 gave a 62% match with residues 9-21 of an AP from Haemophilus influenzae . The enzyme was inactivated by chelating agents, bestatin, p-hydroxymercuribenzoate and some heavy metals . Cobalt ions restored EDTA-inactivated activity but did not reverse inhibition by 1,10-phenanthroline . In addition, bestatin and 1,10-phenanthroline had an inhibitory effect on the batch growth of F . nucleatum in a complex medium in which peptidase activities would be nutritionally essential . No such inhibition was observed in a chemically defined medium in which growth was not dependent upon peptidase activities . The peptidase described in this paper therefore appears to be a cobalt-activated metallo-AP which, together with other peptidases, is considered to be important in the survival of F . nucleatum in the subgingival environment of the mouth.

Fed Regist, 1998 Sep 3, 63(171), 47026 - 31
Proposed vaccine information materials for hepatitis B, Haemophilus influenzae type b (Hib), Varicella (chickenpox), and measles, mumps, rubella (MMR) vaccines--CDC . Notice with comment period; Mathematical models of Haemophilus influenzae type b; Wellcome Trust for Epidemiology and Infectious Disease, Zoology Department, Oxford UniversityA review of empirical studies and the development of a simple theoretical framework are used to explore the relationship between Haemophilus influenzae type b (Hib) carriage and disease within populations . The models emphasize the distinction between asymptomatic and symptomatic infection . Maximum likelihood methods are used to estimate parameter values of the models and to evaluate whether models of infection and disease are satisfactory . The low incidence of carriage suggests that persistence of infection is only compatible with the absence of acquired immunity to asymptomatic infection . The slight decline in carriage rates amongst adults is compatible with acquired immunity, but could be a consequence of reduced contacts . The low rate of disease observed in adulthood cannot be explained if protection from disease is a product of previous detectable exposure to Hib alone . We estimate an R0 of 3.3 for Hib in developed countries, which suggests that current immunization programmes may eliminate the infection . Analysis of the disease data set suggests the absence of maternal immunity and increased susceptibility to disease in the oldest age classes.

Respirology, 1998 Jun, 3(2), 107 - 12
Kartagener's syndrome: a re-visit with Chinese perspectives; Tsang KW et al.; The objective of this study was to evaluate the clinical, radiological investigation profiles, and ciliary function and ultrastructure in Chinese patients with Kartagener's syndrome (presence of dextrocardia, sinusitis and bronchiectasis) . All patients with dextrocardia were assessed for the presence of sinusitis and bronchiectasis in our hospital network . Patients identified with Kartagener's were assessed when they were at steady state for their bronchiectasis . Seven cases (4 males; mean age 34.9 years) were identified and systematically reviewed . The mean 24 h sputum volume was 26.6 +/- 32.77 mL/day and the patients suffered from a mean of 2.9 exacerbations/year . Nasal symptoms (anosmia in one, obstruction in six and persistent discharge in three patients) were common . Only two cases (1 M) were married and both had normal fertility . Lung function assessment showed a mean FEV1/FVC of 83.3 +/- 38.78/86.5 +/- 36.72 (% predicted) with little reversibility . High resolution computerized tomography (HRCT) revealed bronchiectactic involvement of the lower lobes in seven and middle lobe/lingula in four cases . Assessment of alpha-1-anti-trypsin, aspergillus precipitins, auto-antibodies and serology for Pseudomonas pseudomallei was normal . Sputum culture yielded Pseudomonas aeruginosa in three, Haemophilus influenzae in three and commensals in one case . Phase contrast microscopy assessment of respiratory cilia, obtained by brushing the inferior turbinate, revealed that most of the mucosa was unciliated . The mean ciliary beat frequency was 5.2 +/- 6.76 Hz (range 0-13.7; normal range 12-18 Hz) . Four patients had immotile cilia whilst the rest had normal ciliary movement . Transmission electron microscopy showed the absence of dynein arms in four patients . The results of this study show that patients with Kartagener's syndrome may have normal ciliary ultrastructure and the absence of dynein arms is not necessarily associated with ciliary immotility . The presence of ciliary immotility might have prognostic value as these patients appear to have more active bronchiectasis . Our experience on this series should help clinicians in the investigation and management of these patients.

Acta Microbiol Pol, 1998, 47(1), 7 - 17
Identification of the second attachment site for HP1 and S2 bacteriophages in Haemophilus influenzae genome; Skowronek K; Presented data demonstrate that both HP1c1 and S2 bacteriophages of Haemophilus influenzae can use two related attB sites on the host chromosome . The first indication comes from the analysis of the whole genome sequence of H . influenzae Rd in which a second region of nucleotide sequence identical with the known attB site was detected . The location of both attB sites agrees with results of earlier field-inversion gel electrophoresis (FIGE) analysis of S2 and HP1c1 lysogens of H . influenzae . Functionality of cloned attB sites in the integration process of both phages was confirmed using in vivo integrase-dependent recombination system in Escherichia coli . Presented results seem to extend previously described similarities between S2 and HP1c1 phages.

Eur J Epidemiol, 1998 Jun, 14(4), 405 - 12
Molecular epidemiology and phylogenetic analysis of Haemophilus parainfluenzae from chronic obstructive pulmonary disease exacerbations; Privitera A et al.; This study was undertaken to characterize serial Haemophilus parainfluenzae strains from epidemiologically unrelated chronic obstructive pulmonary disease (COPD) patients and from healthy carriers . A comprehensive approach was used including different phenotypical and molecular typing methods: biotyping, antibiotyping, conventional ribotyping, pulsed field gel electrophoresis (PFGE) assay, and PCR-ribotyping . Conventional ribotyping and PFGE analysis were confirmed as excellent procedures to differentiate isolates of the same species and biotype . Conversely, in our study, PCR-ribotyping proved to be suitable for taxonomic purposes, unambiguously identifying H . parainfluenzae from H . influenzae but not discriminating strains at the intraspecific level for epidemiological typing . Phylogenetic analysis of restriction fragment length polymorphism (RFLP) data of sequences related to the rrn operon demonstrated that H . parainfluenzae strains associated to COPD are spread among many diverging lineages.

Microb Comp Genomics, 1997, 2(4), 313 - 21
Tn916 transposition in Haemophilus influenzae Rd: preferential insertion into noncoding DNA; Nelson KE et al.; The availability of completely sequenced genomes has created an opportunity for high throughput mutational studies . Using the conjugative transposon Tn916, a pilot project was initiated to determine the efficiency of gene disruption in the first completely sequenced bacterium, Haemophilus influenzae Rd strain KW20 . DNA was isolated from Tn916-mutagenized cells, and the point of transposon insertion was determined by inverse PCR, DNA sequencing, and mapping to the wild-type genome sequence . Analysis of the insertion sites at the nucleotide level demonstrated a biased pattern of insertion into regions rich in stretches of A's and T's . Although Tn916 integrated at multiple dispersed positions throughout the chromosome, 9 of 10 insertion events occurred in noncoding, intergenic DNA . It was determined that the intergenic DNA was over 5% more A + T-rich than that of protein coding sequences . This suggests that A + T-rich sequences similar to the Tn916 insertion site would be more likely to reside in the intergenic DNA . In an effort to identify other likely sites for transposon integration, a hidden Markov model of the consensus target insertion site was derived from the Tn916-H . influenzae junction fragments and searched against the entire genome . Eighty percent of the 30 highest-scoring predicted Tn916 target sites were from intergenic, nonprotein-coding regions of the genome . These data support the hypothesis that Tn916 has a marked preference for insertion into noncoding DNA for H . influenzae, suggesting that this mobile element has evolved to minimize disruption of host cell function on integration.

Microb Comp Genomics, 1997, 2(4), 299 - 312
Codon-anticodon assignment and detection of codon usage trends in seven microbial genomes; Nakamura Y et al.; We have assigned codon-anticodon recognition patterns for the whole set of transfer RNAs of Haemophilus influenzae Rd, Methanococcus jannaschii, and Synechocystis sp . PCC6803 using sequence information derived from the complete genome sequence of these organisms and have tabulated them along with those previously reported for Escherichia coli, Mycoplasma genitalium, Mycoplasma pneumoniae, and Saccharomyces cerevisiae . Using the resulting codon-anticodon tables, the bias in codon usage of genes encoding the entire protein and ribosomal protein complement of each of the seven microbial genomes was analyzed . Then, the codon adaptation index (CAIrp) for each protein gene was calculated using the codon usage preference of the ribosomal protein genes of the corresponding organism . Of the seven genomes examined, six showed CAIrp scores that roughly coincided with the expected level of gene expression . The result demonstrates that CAIrp analysis may be useful for prediction of the expression level of unknown genes when all or at least considerable portions of the genome sequence are available.

Microb Comp Genomics, 1997, 2(2), 141 - 58
The aroQ and pheA domains of the bifunctional P-protein from Xanthomonas campestris in a context of genomic comparison; Gu W et al.; The gene (denoted aroQp.pheA) encoding the bifunctional P-protein (chorismate mutase-P/prephenate dehydratase) from Xanthomonas campestris was cloned . aroQp.pheA is essential for L-phenylalanine biosynthesis . DNA sequencing of the smallest subclone capable of functional complementation of an Escherichia coli phenylalanine auxotroph revealed a putative open reading frame (ORF) of 1200 bp that would encode a 43,438-Da protein . AroQp.PheA exhibited 51% amino acid identity with a Pseudomonas stutzeri homologoue and greater than 30% identities with AroQp.PheA proteins from Haemophilus influenzae, Neisseria gonorrhoeae, and a number of enteric bacteria . AroQp.PheA from X . campestris, when expressed in E . coli, possesses a 40-residue amino-terminal extension that is lysine-rich and that is absent in all of the AroQp.PheA homologues known at present . About 95% of AroQp.PheA was particulate and readily sedimented by low-speed centrifugation . Soluble preparations of cloned AroQp.PheA exhibited a native molecular mass of 81,000 Da, indicating that the active enzyme species is a homodimer . These preparations were unstable after purification of about 40-fold, even in the presence of glycerol, which was an effective protectant before fractionation . When AroQp.PheA was overproduced by a T7 translation vector, unusual inclusion bodies having a macromolecular structure consisting of protein fibrils were observed by electron microscopy . Insoluble protein collected at low-speed centrifugation possessed high catalytic activity . The single band obtained via SDS-PAGE was used to confirm the translational start via N-terminal amino acid sequencing . A perspective on the evolutionary relationships of monofunctional AroQ and PheA proteins and the AroQp.PheA family of proteins is presented . A serC gene located immediately upstream of X . campestris aroQp.pheA appears to reflect a conserved gene organization, and both may belong to a single transcriptional unit.

Microb Comp Genomics, 1997, 2(2), 113 - 21
A whole genome shotgun gene fusion method for isolation of translation initiation sites in Escherichia coli: identification of Haemophilus influenzae translation initiation sites in E . coli; McKenney K et al.; We have developed a new method for isolating translation initiation sites based on the expression of Haemophilus influenzae Rd gene fusions with the Escherichia coli galactokinase (galK) gene . We cloned random DNA fragments of H . influenzae Rd DNA into a plasmid vector containing the galK coding sequence from which the translation initiation site (the ribosome binding site and translation initiation codon) had been removed . A subset of the cloned DNA fragments contained translation initiation sites that, when fused to the galK gene, produced active galactokinase and complemented the host galK mutation . Molecules expressing galactokinase activity were isolated and characterized by DNA sequence analysis, and the sequences were aligned with the recently completed whole genomic sequence of H . influenzae Rd . Translation initiation sites for known, hypothetical, and new genes were identified . Translation initiation sites internal to the coding sequences of a number of genes were identified, suggesting that internal translation initiation sites are common, especially in large genes . This shotgun method provides functional information on translation initiation sites and helps to define gene coding sequences.

Microb Comp Genomics, 1996, 1(4), 281 - 91
Fast comparison of a DNA sequence with a protein sequence database; Huang X; We describe a computer program, named DNA-Protein Search (DPS), for comparing a megabase DNA sequence with a protein sequence database . The DPS program addresses the problems of frameshifts and introns in the DNA sequence . The DPS program was used to compare each of the following sequences with the Swiss-Prot database: the 1.8-megabase sequence of the Haemophilus influenzae Rd genome, the 0.58-megabase sequence of the Mycoplasma genitalium genome, and the 0.56-megabase sequence of Saccharomyces cerevisiae chromosome VIII . The comparisons found new regions that are similar to protein sequences . The sensitivity of DPS was evaluated using as test data the known coding regions of the three DNA sequences . The results demonstrate that the DPS program is a useful tool for finding the coding regions of the DNA sequence . The DPS program uses an order of magnitude less computer memory and is several times faster than the BLASTX program.

Eur J Biochem, 1998 Jun 15, 254(3), 655 - 61
Bacterial selenocysteine synthase--structural and functional properties; Tormay P et al.; Selenocysteine synthase from Escherichia coli is a pyridoxal-5'-phosphate-containing enzyme which catalyses the conversion of seryl-tRNA(Sec) into selenocysteyl-tRNA(Sec) . Analysis of amino acid sequences indicated that selenocysteine synthase belongs to the alpha/gamma superfamily of pyridoxal-5'-phosphate-dependent enzymes . To identify the lysine residue carrying the prosthetic group, the genes coding for the selenocysteine synthases from Moorella thermoacetica and Desulfomicrobium baculatum were cloned and sequenced and their derived amino acid sequences were aligned with those from E . coli and Haemophilus influenzae . Three lysine residues were found to be conserved; they were mutated into asparagine and one of them, Lys295, was found to be essential for activity . Proteolytic fragmentation of the E . coli enzyme reduced with borohydride, and mass-spectrometric and sequence analysis of the chromophoric peptide proved that Lys295 was modified . Kinetic analysis of the enzyme showed that thiophosphate served as a substrate leading to cysteyl-tRNA(Sec) synthesis, albeit with a 330-fold lower catalytic efficiency . Selenide and, to a much lesser degree, sulfide could also be used by the enzyme but only at much higher concentrations . These data together with the finding that selenophosphate synthetase is highly specific for selenide indicate that the phosphate moiety of selenophosphate provides selenocysteine synthase with the discrimination specificity against sulfur.

Antimicrob Agents Chemother, 1998 Aug, 42(8), 2138 - 40
In vitro activities of the ketolide HMR 3647 against recent gram-positive clinical isolates and Haemophilus influenzae; Barry AL et al.; The ketolide HMR 3647 (previously RU 66647) was evaluated against 2, 563 recent clinical isolates of gram-positive pathogens and 200 Haemophilus influenzae isolates . HMR 3647 was active against macrolide-resistant streptococci, including pneumococci, but was not active against macrolide- or lincosamide-resistant staphylococci . Against H . influenzae, the potency of HMR 3647 was similar to that of azithromycin.

Rev Cubana Med Trop, 1997, 49(1), 38 - 42
{Characterization of Haemophilus influenzae strains using sugar fermentation}; Llanes Caballero R et al.; 64 Haemophilus influenzae strains circulating in Havana City during a year were characterized by the carbohydrate fermentation method for the first time in Cuba . The fermentative pattern D was the most frequently found . Patterns D and G together were 72% of the total of strains studied . The combination of the carbohydrate fermentation with serotyping and biotyping allowed a greater differentiation of strains (14 groups) . Patterns A, B, C and F appeared in children over 6 months of age, and pattern G in the group from 6 to 18 . Patterns D and G predominated in the bacterial meningoencephalitis . A higher heterogeneity was observed among the strains isolated from acute respiratory infections . Some of the advantages of the Haemophilus influenzae strains subtyping method are stressed, such as: simplicity, easiness to be applied and interpreted, and the fact that it is not necessary a qualified personnel or a specialized laboratory for its implementation.

Pediatrics, 1998 Aug, 102(2 Pt 1), 296 - 9
Serum interleukin-6 in bacterial and nonbacterial acute otitis media; Heikkinen T et al.; BACKGROUND: Increasing prevalence of antibiotic-resistant bacteria is a serious clinical problem that calls for reduction of unnecessary use of antibiotics . Acute otitis media (AOM) is the most common reason for antibiotic therapy in the United States . Approximately 30% of AOM cases do not have a bacterial etiology . Rapid identification of these cases could help withhold unnecessary antibiotic treatment . OBJECTIVE: To determine the usefulness of serum levels of interleukin-6 (IL-6), an acute phase cytokine shown to be a reliable marker of neonatal bacterial infection, in differentiation between bacterial and nonbacterial AOM in children . STUDY DESIGN: IL-6 was measured in stored serum samples from 184 children (mean age, 22 months) with AOM who were enrolled in antibiotic efficacy trials at our department . The samples were obtained at enrollment and at 9 to 12 days after initiation of antibiotic therapy . Sera from 21 uninfected children (mean age, 23 months) were used as controls . The etiology of AOM was determined by bacterial and viral cultures as well as respiratory syncytial virus antigen detection in the middle ear fluids obtained by tympanocentesis . RESULTS: Bacterial etiology of AOM was confirmed in 125 children (68%), whereas in 59 children (32%) no bacterial pathogen could be detected in the middle ear fluid . Children with bacterial AOM had significantly higher IL-6 levels than those with nonbacterial AOM (median, 11.5 vs 3.7 pg/mL) . However, this difference was almost entirely attributable to pneumococcal AOM specifically . IL-6 levels in children with AOM caused by Streptococcus pneumoniae were significantly higher (median, 40.1 pg/mL) than in AOM caused by Haemophilus influenzae (7.3 pg/mL) or Moraxella catarrhalis (6.8 pg/mL) . At the cutoff value of 30 pg/mL, the specificity of IL-6 for detection of pneumococcal AOM was 91% with a sensitivity of 61%, but its sensitivity for detection of bacterial AOM in general was only 27% . CONCLUSIONS: Low levels of IL-6 do not rule out bacterial etiology of AOM in general; therefore, IL-6 is not sensitive enough as a marker of bacterial AOM . Surprisingly, serum IL-6 levels in pneumococcal AOM were significantly higher than the levels associated with other bacterial AOM, and serum IL-6 levels of >30 pg/mL were highly specific for pneumococcal AOM . These findings suggest a distinctive role for S pneumoniae in the pathogenesis of AOM.

FEMS Microbiol Lett, 1998 Jul 15, 164(2), 269 - 73
Facile construction of mutations in Haemophilus ducreyi using lacZ as a counter-selectable marker; Bozue JA et al.; Haemophilus ducreyi is a Gram-negative bacterium which is the causative agent of chancroid, an ulcerative sexually transmitted disease . In order to understand the pathogenesis of H . ducreyi disease, studies designed to identify potential virulence determinants and construct mutants deficient in the elaboration of these determinants have been undertaken in several laboratories . At the present time, construction of isogenic mutants is accomplished by electroporation of linearized DNA containing insertionally inactivated H . ducreyi genes followed by selection for the resistance marker encoded on the inactivated gene . In our experience, certain mutants are difficult to construct using this procedure . In the construction of strains containing lacZ as a reporter gene, we observed that the growth of lacZ expressing H . ducreyi was inhibited in the presence of X-gal . We have exploited this observation to develop a new strategy for the construction of isogenic H . ducreyi mutants.

FEMS Microbiol Lett, 1998 Jul 15, 164(2), 289 - 94
Cloning and sequencing of a 16S/23S ribosomal spacer from Haemophilus parainfluenzae reveals an invariant, mosaic-like organisation of sequence blocks; Privitera A et al.; A 16S/23S ribosomal spacer from a Haemophilus parainfluenzae rrn locus was cloned and sequenced . Analysis of PCR-amplified genomic fragments showed that this region is strongly conserved among unrelated isolates; computer analysis of database homologies showed that the spacer consists of sequence blocks, arranged in a mosaic-like structure, with strong homologies with analogous blocks present in the spacer regions of Haemophilus influenzae, Haemophilus ducreyi and Actinobacillus spp . It also contains a tRNA(Glu) gene, which is highly homologous to tRNA(Glu) genes found in spacers of other species . These data strongly support the hypothesis that recombination events are involved in the organisation of the sequence of the spacer, as a result of horizontal gene transfer.

Vaccine, 1998 May-Jun, 16(9-10), 1004 - 8
Antibody responses of three Haemophilus influenzae type b conjugate vaccines after one, two and three doses in Filipino children; Capeding MR et al.; Differences in the magnitude of antibody response after one, two or three doses of Haemophilus influenzae type b conjugate vaccines have been reported which may influence decision-making regarding which vaccine should be used . This is of particular importance in developing countries where children may not receive a full immunization series and the vaccination schedule may be delayed . Serum antibody responses to three Hib capsular polysaccharide protein conjugate vaccines (PRP-OMP, HbOC and PRP-T) were evaluated in 102 Filipino infants . Vaccination was carried out at 6, 10 and 14 weeks of age based on the national Expanded Programme on Immunization (EPI) schedule together with diphtheria-tetanus-pertussis, hepatitis B and oral poliomyelitis vaccines . Sera were collected at 6 weeks and 1 month after each vaccination . Anti-Hib polysaccharide antibody concentrations were determined by Farrtype radioimmunoassay (RIA) and enzymeimmunoassay (EIA), Following the first dose, the geometric mean concentrations (GMC, micrograms ml-1) for PRP-OMP, HbOC and PRP-T were 0.69, 0.27 and 0.38, respectively . After two doses, there was a significant response (P < 0.05) to PRP-OMP and PRP-T (0.89 and 1.47) but not for HbOC (0.37) . Differences in the GMC after the primary series were significant (pairwise P < 0.05): GMC was highest for PRP-T (4.0), followed by HbOC (1.6) and PRP-OMP (1.1) . All three Hib vaccines were immunogenic when given in the local EPI schedule in Filipino infants although significant differences in the kinetics and magnitude of antibody responses were noted . The anti-Hib antibody concentrations determined by RIA and EIA were also compared in order to validate the latter for use in laboratories where it is feasible . There was a good correlation (r2 = 76%; P = 0.0001) in the Hib antibody titres obtained by both assays.

Vaccine, 1998 May-Jun, 16(9-10), 921 - 7
Safety and immunogenicity of an Haemophilus influenzae type b-tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-pertussis (DTP) combination vaccine administered in a dual-chamber syringe to infants in Belgium and Chile; Hoppenbrouwers K et al.; To document any unexpected differences in the immune response between study populations and to evaluate immunogenicity and safety of a simplified presentation (dual-chamber syringe) of an Haemophilus influenzae type b-tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-pertussis (DTP) combination vaccine, a multicentre, randomized, comparative study was conducted in Belgium and Chile . A total of 537 healthy infants, 270 in Chile and 267 in Belgium, received PRP-T and DTP vaccines combined in a dual-chamber syringe (D-Ch group, DTP/PRP-T, reconstituted by pressing the plunger of the syringe immediately before injection, n = 239) or combined in a single-chamber syringe (C-In group, DTP@PRP-T, reconstituted immediately before injection, n = 61) or in separate injections (S-In group, DTP + PRP-T, simultaneously injected at separate sites, n = 237) at 3, 4, and 5 months of age . Serum samples were collected before vaccination and at 6 months of age . In the D-Ch group, the incidence of adverse events was comparable to administration of DTP vaccine alone . Higher rates of local and systemic reactions were observed in the Chilean population, possibly due to differences in surveillance practice . The immune response to each vaccine component compared well to that of the separate administration of PRP-T and DTP vaccines, except for higher post-immunization anti-PRP geometric mean titre (GMT) values after separate injections (25.6 micrograms mL-1) than after combined injection with the dual-chamber syringe (17.6 micrograms mL-1) (p = 0.001) . An unexpected 'syringe' effect was seen: a greater post-immunization anti-PRP GMT was observed in the D-Ch group (17.6 micrograms mL-1) than in the C-In group (7.7 micrograms mL-1) (p = 0.0001) . Whereas pre-immunization GMTs of some antibodies were significantly lower in Chilean than in Belgian infants, the post-immunization GMTs of Chilean infants were two to three times greater for all of the antibodies studied (p < 0.005) . Differences in reactogenicity and in the immune response between the study populations or the different vaccine presentations were striking, but are probably of no clinical relevance . The convenient dual-chamber syringe presentation of DTP and PRP-T vaccines is safe and highly immunogenic.

J Trop Pediatr, 1998 Jun, 44(3), 167 - 9
Indications and benefits of computed tomography in childhood bacterial meningitis; Daoud AS et al.; Over a 5 year period, 58 children with acute bacterial meningitis underwent computed tomography (CT) of the head . The major stated indications were partial, complex, or prolonged seizures in children younger than 5 years (60 per cent) and prolonged fever in the case of those older than 5 years (60 per cent) . Abnormal findings on CT scan were seen in 27 (47 per cent); the remaining 31 (53 per cent) patients had normal or only non-specific dilatation of spaces containing cerebrospinal fluid (CSF) or basilar enhancement . The commonest CT abnormalities were seen in those patients who presented with complex seizure disorders . The commonest abnormal findings were subdural collection (33 per cent) followed by hydrocephalus (7 per cent) . Subdural collection was seen mainly in patients with Haemophilus influenzae bacterial meningitis (90 per cent) while hydrocephalus was mainly seen in tuberculous meningitis . Positive findings of obvious therapeutic clinical relevance were present in only six cases (10 per cent) . From the study we concluded that head CT provides an accurate means of diagnosing intracranial complications of bacterial meningitis, but it must be used conservatively as it has limited therapeutic applications in children with complicated bacterial meningitis . Computed tomography is indicated mainly in children with persistent neurologic dysfunction like complex seizure disorder, and is of little value in children with prolonged fever alone.

Curr Opin Pulm Med, 1998 May, 4(3), 173 - 9
Antibiotic resistance in respiratory pathogens; Dominguez MA et al.; Antibiotic resistance in respiratory pathogens has dramatically increased during recent years . Resistance to penicillin and multiple antimicrobial agents in pneumococci and resistance to ampicillin in Moraxella catarrhalis and Haemophilus influenzae, as a result of betalactamase production, have become highly prevalent worldwide . The emergence of multiple drug-resistant tuberculosis in different countries is of concern, and has become a therapeutic challenge.

APMIS, 1998 May, 106(5), 547 - 52
Antibody response in six HACEK endocarditis cases under therapy; Zbinden R et al.; The antibody response to bacteria of the so-called HACEK group, i.e . Haemophilus spp., Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens and Kingella kingae, was measured in sera of six patients with endocarditis . The corresponding isolates from their blood cultures were identified by conventional methods, including reactions for nitrate reduction and catalase as well as acid production from sugars . Crude antigens were prepared by glycine extraction and sonification of the blood culture isolates, and used to determine titers by complement fixation . A patient with Haemophilus parainfluenzae bacteremia received a short course of antibiotic therapy, and relapsed with spondylitis and endocarditis 5 months later . Titers of sera against his own isolate rose from 1:40 to 1:320 and fell to 1:40 after therapy within one year . A patient with C . hominis endocarditis had a similarly prolonged course . The complement fixation titer against his own isolate was already 1:240 before antibiotics were administered . Another patient with C . hominis endocarditis presented a titer of 1:320 2 weeks after the diagnosis . These three patients revealed C-reactive protein values over 50 mg/l in the first serum sample . Decrease of both antibody titers and C-reactive protein values correlated with clinical improvement . Two patients with prosthetic valve replacement 5 months earlier developed C . hominis and K . kingae endocarditis, respectively . At admission, C-reactive protein values were 64 and 82, respectively, and therapy was instituted immediately . The first sera were received 3 and 6 weeks, respectively, after isolation of the corresponding blood culture isolates and revealed already low titers, i . e . 1:80 and 1:60, respectively . A woman with A . actinomycetemcomitans endocarditis received immediate therapy and did not develop titers against her own isolate . CRP was 100 at admission and remained over 50 5 weeks later . We conclude that the complement fixation assay with individual antigen preparations was easy to perform and allowed monitoring of the antibody response in 5 of 6 HACEK endocarditis cases under therapy, but the usefulness of this method to find culture-negative HACEK endocarditis needs to be established.

APMIS, 1998 May, 106(5), 539 - 46
Characterization of mechanisms involved in adherence of Haemophilus ducreyi to eukaryotic cells; Frisk A et al.; The adherence of Haemophilus ducreyi to eukaryotic cells of various origins was investigated by means of a microassay using radiolabelled bacteria . The influence of physicochemical conditions and of different inhibitors on adherence to HEp-2 cells and human fibroblasts was examined . H . ducreyi strains manifested substantial adherence capacity (range, 11-38% of inoculum) to different cells, not discriminating between human and animal origin . The level of adherence was temperature-dependent, being substantially decreased by incubation at 4 degrees C, but was unaffected in the pH range 4-10 . The adherence level was significantly reduced in the presence of sodium chloride or tetramethylurea (a hydrophobic bond-breaking agent) . In addition, H . ducreyi bacteria manifested a pronounced capacity for binding Congo red to the surface, in comparison with the low binding ability of H . influenzae type b . This further indicates hydrophobic domains to be accessible on the surface of H . ducreyi . Inhibition studies with bacterial EDTA extract, sialic acid, heparin and heparan sulphate resulted in a significant reduction in adherent bacteria . However, adherence was not inhibited with crude 24 kDa pili material, LOS of H . ducreyi or fibronectin . Neither crude nor purified 24 kDa protein of H . ducreyi bacteria showed any capacity to bind monolayers of HEp-2, HeLa or human fibroblasts cells, as tested by immunoblot using specific polyclonal antibodies . The overall results suggest that adherence of H . ducreyi to eukaryotic cells is not specific to a particular cell type, human or animal . Adherence to HEp-2 cells involves a multiplicity of factors such as ionic and hydrophobic forces, and can be mediated by tissue heparin/heparan sulfate proteoglycans . However, specific binding to HEp-2 cells does not seem to be mediated by the 24 kDa pili protein of H . ducreyi.

Ear Nose Throat J, 1998 Jun, 77(6 Suppl), 13 - 5
Measuring antibiotic levels in otitis media; Thoroddsen E; Antibiotic concentrations in serum and middle ear effusion (MEE) are important in determining treatment success in acute otitis media, but studies to measure concentration levels are often performed in chronically infected patients where there is little inflammation . In this open, single-center study, 26 patients with acute otitis media were enrolled to assess antibiotic penetration in inflamed ears . Of the 26 patients, 4 were non-evaluable, 6 formed a control group and the others were randomized into three groups . Each of the three groups was given a single oral dose of cefuroxime axetil suspension, 15 mg/kg . Food was administered approximately 20 minutes before the drug in order to maximize drug absorption . Cefuroxime concentrations in serum and MEE were assessed at 2-3 (group 1), 3-4 (group 2) and 4-5 (group 3) hours following dosing . Sampling of MEE was performed with tympanocentesis under local anesthesia and the drug was assayed by HPLC-mass spectrometry . The serum concentrations of cefuroxime were found to be above the minimal inhibitory concentration (MIC) for penicillin-sensitive Streptococcus pneumoniae for 100% of the dosing interval and 42% of the time for intermediate-resistant strains . For both Haemophilus influenzae and Moraxella catarrhalis, serum cefuroxime levels were above the MIC for 42% of the time between doses . This study indicates that cefuroxime axetil penetrates the inflamed middle ear effectively in acute otitis media after oral dosing . Serum levels were maintained above the MICs of important bacterial pathogens in otitis media for more than 5 hours after dosing, which is equivalent to 42% of the dosing interval . Thus, the important statistic of 40-50% of time above MIC, required for beta-lactam antibiotics to produce the maximal bacteriological cure rate of 80-85%, is achieved.

N Z Med J, 1998 Jun 12, 111(1067), 208 - 10
The changing face of epiglottitis in Canterbury 1970-1996; Sivertsen LM et al.; AIM: To record changes in the epidemiology, clinical presentation and management of the potentially fatal childhood disease, epiglottitis . METHODS: The case records of 69 children presenting to Christchurch Hospital with acute epiglottitis over the last 27 years were reviewed to confirm the diagnosis and to record clinical data . RESULTS: The incidence of epiglottitis increased significantly up until 1992 . Since then there have been only two cases . This decline coincides with the availability of the Haemophilus influenzae Group b vaccine from 1993 . Haemophilus influenzae was cultured in 86% of children . With the emergence of ampicillin resistant strains, antimicrobial therapy has changed to cephalosporins . Changes in airway management have also occurred, with the replacement of tracheostomy by elective naso-tracheal intubation . CONCLUSIONS: The incidence of epiglottitis in New Zealand has followed trends reported overseas . The longer term implications of this declining incidence following introduction of vaccination are not known . It is important however, that doctors still know how to recognize and manage acute epiglottitis in children and adults.

Prim Care, 1998 Sep, 25(3), 633 - 48
Microbiology of common infections in the upper respiratory tract; Brook I; The management of upper respiratory tract infections has become more difficult because of the recent increase in the number of penicillin-resistant organisms . The bacteria that predominate in otitis media and sinusitis can resist penicillin through the production of the enzyme beta-lactamase (Haemophilus influenzae and Moraxella catarrhalis in acute infections and Staphylococcus aureus and Prevotella and Fusobacteria spp in chronic infections) or through changes in penicillin-binding sites (Streptococcus pneumoniae) . beta-lactamase-producing bacteria can express their pathogenicity directly through their ability to cause infections and indirectly by production of the enzyme, thus protecting penicillin-susceptible pathogens from penicillins . This phenomenon may explain penicillin's failure in the treatment of Group A beta-hemolytic streptococcal (GABHS) tonsillitis . An additional cause for penicillin failure is the absence among the normal tonsillar bacterial flora of streptococcal species that are capable of interfering with the growth of GABHS . Proper use of antimicrobial therapy, including those therapies that are effective against penicillin-resistant bacteria, is the cornerstone of management of upper respiratory tract infections.

Infect Immun, 1998 Aug, 66(8), 3523 - 6
CD1 presents antigens from a gram-negative bacterium, Haemophilus influenzae type B; Fairhurst RM et al.; Human CD1 is a family of nonpolymorphic major histocompatibility complex class I-like molecules capable of presenting mycobacterial lipids, including lipoarabinomannan (LAM), to double-negative (DN; CD4(-) CD8(-)) as well as CD8(+) T cells . Structural similarities between LAM and the capsular polysaccharides of gram-negative bacteria led us to consider the latter as candidate CD1 ligands . We derived two CD1-restricted DN T-cell populations which proliferated to Haemophilus influenzae type b (Hib) antigen . One T-cell population also proliferated to proteinase K-treated Hib antigen, suggesting that it recognized a nonpeptide . Our work thus expands the universe of T cell antigens to include nonpeptides distinct from mycobacterial lipids and suggests a potential role for CD1-restricted T cells in immunity to Hib.

Proc Natl Acad Sci U S A, 1998 Jul 21, 95(15), 8927 - 32
Systematic identification of essential genes by in vitro mariner mutagenesis; Akerley BJ et al.; Although the complete DNA sequences of several microbial genomes are now available, nearly 40% of the putative genes lack identifiable functions . Comprehensive screens and selections for identifying functional classes of genes are needed to convert sequence data into meaningful biological information . One particularly significant group of bacterial genes consists of those that are essential for growth or viability . Here, we describe a simple system for performing transposon mutagenesis on naturally transformable organisms along with a technique to rapidly identify essential or conditionally essential DNA segments . We show the general utility of this approach by applying it to two human pathogens, Haemophilus influenzae and Streptococcus pneumoniae, in which we detected known essential genes and assigned essentiality to several ORFs of unknown function.

Bull Acad Natl Med, 1998, 182(3), 567 - 77; discussion 577-9
{Reflections on the effectiveness of the new combined vaccines}; Begue P; The combination vaccines are very useful to reduce the number of contacts required to immunize a child fully and to improve the vaccine coverage . Recently the new combinations between Haemophilus Influenzae vaccine (PRP-T) and pertussis vaccines in D-T-P (IVP) combined vaccines have suggested interferences with immunogenicity for PRP-T vaccines . The interference for pertussis antibodies is not significative . The depression of antiPRP antibodies is shown with the whole-cell pertussis vaccine, but the level of antibodies is related to a good protective efficacy . Inversely, when PRP-T vaccine is combined with acellular pertussis vaccines, the antibodies levels are lower, especially the number of children with a level higher than 1 mcg/ml . At the present time, these combinations between PRP-T vaccines and acellular pertussis vaccines are not recommended for primary immunization in infants in France . Such constations emphasize the necessity to perform wide comparative trials to test immunogenicity for all the next combinations between old and new vaccines . A decrease in immunogenicity of combination vaccines is acceptable as long as protective efficacy is preserved . It is possible that the growing number of new vaccines to combine will be limited to keep a clinical efficacy.

FEMS Microbiol Lett, 1998 Jun 15, 163(2), 135 - 42
Expression of iron binding proteins and hemin binding activity in the dental pathogen Actinobacillus actinomycetemcomitans; Graber KR et al.; Actinobacillus actinomycetemcomitans was found to express a polypeptide immunologically related to the Neisseria gonorrhoeae FbpA iron binding protein . In addition, the expression of hitB and hitC homologs was detected by Northern blot analysis . This periodontal pathogen also expresses a polypeptide homologous to the 31-kDa Haemophilus influenzae protein, which shows amino acid sequence homology with the FimA and YfeA proteins from Streptococcus parasanguis and Yersinia pestis, respectively . Both A . actinomycetemcomitans protein homologs were located within the periplasmic space, and their synthesis was regulated by the iron and hemin concentration of the culture medium . Southern and Western blot analysis together with molecular cloning revealed the presence of a Fur-like repressor, which may control the iron regulation of gene expression in this bacterium . Cultivation in the presence of hemin or Congo red revealed the ability of this organism to bind hemin . This binding activity was further confirmed by isolating Escherichia coli DH5 alpha clones that produced red and brown colonies on agar plates containing Congo red and hemin, respectively, after transformation with an A . actinomycetemcomitans gene library.

Biochemistry, 1998 Jul 21, 37(29), 10478 - 87
Hydrolysis of N-succinyl-L,L-diaminopimelic acid by the Haemophilus influenzae dapE-encoded desuccinylase: metal activation, solvent isotope effects, and kinetic mechanism; Born TL et al.; Hydrolysis of N-succinyl-L,L-diaminopimelic acid by the dapE-encoded desuccinylase is required for the bacterial synthesis of lysine and meso-diaminopimelic acid . We have investigated the catalytic mechanism of the recombinant enzyme from Haemophilus influenzae . The desuccinylase was overexpressed in Escherichia coli and purified to homogeneity . Steady-state kinetic experiments verified that the enzyme is metal-dependent, with a Km for N-succinyl-L,L-diaminopimelic acid of 1.3 mM and a turnover number of 200 s-1 in the presence of zinc . The maximal velocity was independent of pH above 7 but decreased with a slope of 1 below pH 7 . The pH dependence of V/K was bell-shaped with apparent pKs of 6.5 and 8.3 . Both L,L- and D,L-diaminopimelic acid were competitive inhibitors of the substrate, but d,d-diaminopimelic acid was not . Solvent kinetic isotope effect studies yielded inverse isotope effects, with values for D2OV/K of 0.62 and D2OV of 0.78 . Determination of metal stoichiometry by ICP-AES indicated one tightly bound metal ion, while sequence homologies suggest the presence of two metal binding sites . On the basis of these observations, we propose a chemical mechanism for this metalloenzyme, which has a number of important structurally defined homologues.

Microbios, 1998, 93(374), 55 - 68
Non-typable Haemophilus influenzae from a single hospital: epidemiological markers; Sanchez Planas L et al.; A total of 51 strains of non-typable Haemophilus influenzae isolated from a single hospital were subjected to analysis of biochemical traits, outer membrane protein (OMP) profiles, lipopolysaccharide (LPS) electrophoresis and antibiotic susceptibility determination in order to establish a method for bacterial typing . Results proved that none of the methods tested were useful for typing purposes, although the data showed that (1) OMP profiles were extremely variable; (2) LPS profiles were uniform; (3) the multiresistant strains manifested different resistance patterns; and (4) biochemically, all strains were closely related.

Scand J Infect Dis, 1998, 30(1), 49 - 51
Aetiology of acute epiglottitis in adults; Trollfors B et al.; In order to determine the aetiology of acute epiglottitis in adults, blood cultures, paired sera and a urine sample were obtained from 54 patients with fever and epiglottitis visualized by indirect laryngoscopy or by direct fibreoptic nasolaryngoscopy . Antibodies were determined against the capsular polysaccharide of Haemophilus influenzae type b (Hib), 3 pneumococcal antigens (a mixture of 23 capsular polysaccharides, C-polysaccharide and pneumolysin) and antistreptolysin O . Acute sera were examined by the polymerase chain reaction (PCR) for DNA of Hib and pneumococci . The urine samples were examined for Hib capsular antigen . Blood cultures were positive in 15 patients . In another 16, serology and/or PCR verified the aetiology . Hib was the cause in 14, pneumococci in 12 and group A streptococci in 5 patients . The aetiology remained unknown in 23/54 patients (43%) . In conclusion, the addition of serology and PCR to blood cultures doubled the possibilities of verifying the aetiology of acute epiglottitis in adults.

Scand J Infect Dis, 1998, 30(1), 5 - 10
Economic evaluation of general childhood vaccination against Haemophilus influenzae type b in Sweden; Garpenholt O et al.; The objective of the study was to evaluate the economic consequences of a general childhood vaccination programme against Haemophilus influenzae type b (Hib) in Sweden . A retrospective pre-vaccination annual cohort of 0-4-y-old children was compared with an annual cohort of the same age group after a complete implemented vaccination program against Hib . The cost analysis shows that vaccination against Hib is cost saving when indirect costs are included in the analysis . In the cost-benefit analysis it is shown that society will gain approximately 88 million Swedish Crowns (SEK) annually when Hib vaccination is totally implemented . In conclusion, general childhood Hib vaccination is a cost-effective public health intervention in Swedish society.

J Chemother, 1998 Jun, 10(3), 195 - 202
Cefaclor: a contemporary look at susceptibility of key pathogens from around the globe; Preston DA et al.; The orally administered cephalosporin antibiotic, cefaclor, has been available for clinical use in many countries since 1979 . Because widespread antibiotic use is often cited as a factor in the emergence of bacterial resistance to antibiotics, we sought to determine the degrees of resistance to cefaclor expressed by key pathogens recently isolated in 10 countries widely distributed around the world . Using the E-test, minimal inhibitory concentrations (MIC) were determined for cefaclor and several comparator antibiotics against approximately 700 fresh clinical isolates of each of six bacterial species . The results demonstrated that > 90% of Haemophilus influenzae (beta-lactamase producing and non-producing), Haemophilus parainfluenzae (beta-lactamase producing and non-producing), Moraxella catarrhalis (> 90% beta-lactamase producing), and methicillin-susceptible Staphylococcus aureus, and 85% of Escherichia coli were susceptible to cefaclor at the NCCLS interpretive breakpoints . MIC distributions showed that there has been no change in the activity of cefaclor against penicillin-susceptible strains of Streptococcus pneumoniae since 1977.

Arch Pediatr Adolesc Med, 1998 Jul, 152(7), 624 - 8
Risk of bacteremia for febrile young children in the post-Haemophilus influenzae type b era; Lee GM et al.; OBJECTIVES: To determine the risk for bacteremia, in the post-Haemophilus influenzae type b era, in a prospective cohort of well-appearing febrile children 3 to 36 months of age with no obvious source of infection; and to compare the predictive abilities of objective criteria in identification of children with occult pneumococcal bacteremia from those at risk . DESIGN: All children seen from 1993 through 1996, 3 to 36 months of age with a temperature of 39.0 degrees C or higher, no identified source of infection (except otitis media), and discharged to home were considered to be at risk for occult bacteremia and included in the study . SETTING: Urban pediatric emergency department . RESULTS: Of 199868 patient visits to the emergency department, 1911 children were considered to be at risk for occult bacteremia . Blood cultures were obtained from 9465 (79%) . A total of 149 blood cultures contained pathogenic organisms, indicating a rate of occult bacteremia of 1.57% (95% confidence intervals: 1.32%-1.83%) . White blood cell count and absolute neutrophil count were the best predictors for occult pneumococcal bacteremia . Using a white blood cell count cutoff value of 15 cells x 10(9)/L (sensitivity, 86%; specificity, 77%; and positive predictive value, 5.1%) would result in the treatment of approximately 19 nonbacteremic children for each bacteremic child treated . CONCLUSIONS: The prevalence of occult bacteremia in children 3 to 36 months old with temperatures of 39.0 degrees C or higher and no obvious source of infection is 1.6% . The white blood cell and absolute neutrophil counts are the most accurate predictors of occult pneumococcal bacteremia and when available should be used if presumptive antibiotic therapy is being considered.

Gene, 1998 Jul 17, 215(1), 37 - 45
Physical and genetic maps of the Leptospira interrogans serovar icterohaemorrhagiae strain Ictero no.1 chromosome and sequencing of a 19-kb region of the genome containing the 5S rRNA gene; Takahashi Y et al.; We report the construction of physical and genetic maps of the chromosome of Leptospira interrogans serovar icterohaemorrhagiae strain Ictero No.1 using pulsed-field gel electrophoresis of DNA fragments generated by digestion with enzymes SrfI, AscI, FseI, and NotI and using reciprocal hybridization . We also sequenced the 19-kilobase (kb) DNA segment including the one gene for 5S rRNA (rrf) of pathogenic Leptospira . The size of the chromosome of the strain Ictero No.1 was estimated to be 4673kb and was found to be similar to those of the chromosomes of the leptospira strains Verdun (serovar icterohaemorrhagiae) and RZ11 (serovar pomona) . The strains Verdun and RZ11 carry a small 350-kb replicon (minichromosome), and the strain Ictero No.1 also contained the same kind of molecule together with the chromosome . The physical maps of the strains Ictero No.1 and Verdun were almost identical, as were the locations of the selected genes, except for the location of one of the 16S rRNA genes . Overall, the genetic organization appeared to be conserved within the serovar icterohaemorrhagiae strains . In the sequenced region, we identified 10 putative ORFs and one rrf sequence, and the transcription orientations were all the same . A homology search for the products deduced from the sequenced data revealed that the orf H exhibited high similarity to malic acid enzyme of Haemophilus influenzae and fumarate hydratase of Escherichia coli (orf J) . The rest of the putative products encoded by ORFs in the sequenced region showed little similarity with the proteins contained in the databases and were considered to be unknown proteins.

J Clin Microbiol, 1998 Aug, 36(8), 2386 - 8
Comparison of broth microdilution method using Haemophilus test medium and agar dilution method for susceptibility testing of Eikenella corrodens; Alcala L et al.; Susceptibility testing of Eikenella corrodens is usually performed by a Mueller-Hinton sheep blood agar dilution (AD) method . However, this method is impractical for testing only a few strains . We compared AD with the broth microdilution method using Haemophilus test medium (HTM) in order to determine the susceptibility of 36 clinical isolates of E . corrodens to eight antimicrobial agents . MICs obtained by the HTM method yielded 95.5 and 84% agreement (within 2 and 1 log2 dilutions, respectively) with those obtained by AD . The HTM method with incubation in CO2 for 48 h was highly reproducible and constitutes an easy alternative for antimicrobial susceptibility testing of E . corrodens.

Eur J Clin Microbiol Infect Dis, 1998 Mar, 17(3), 197 - 201
Provisional quality control parameters and interpretive criteria for testing susceptibility of Streptococcus pneumoniae and Haemophilus influenzae to quinupristin/dalfopristin (RP59500) . Antimicrobial Testing Quality Control Group; Fuchs P et al.; Studies were undertaken to select tentative criteria for susceptibility testing of quinupristin/dalfopristin against Streptococcus pneumoniae and Haemophilus influenzae . Against 612 isolates of Streptococcus pneumoniae, MICs of quinupristin/dalfopristin were < or = 1.0 microg/ml for all but one strain . With a tentative MIC breakpoint of either < or = 1.0 microg/ml or < or = 2.0 microg/ml for susceptible, a disk diffusion zone diameter breakpoint of > or = 19 mm embraced all but two of the susceptible pneumococci; > or = 16 mm included all strains . For Haemophilus influenzae, MICs of quinupristin/dalfopristin clustered near the tentative breakpoints; 91.5% of the MICs were 2.0 to 8.0 microg/ml . This precluded satisfactory performance of the disk diffusion test in discriminating between resistant and susceptible isolates unless MIC breakpoints are modified for this species: clinical experience will be needed before that can be justified . Based on data from a multilaboratory study, the following quality control limits are proposed for Streptococcus pneumoniae ATCC 49619 when testing quinupristin/dalfopristin: 0.25 to 1.0 microg/ml for broth microdilution tests and 19 to 24 mm for disk diffusion tests . For tests of Haemophilus influenzae ATCC 29247, MIC limits are 2.0 to 16 microg/ml; disk tests were very reproducible but are not yet recommended.

Laryngoscope, 1998 Jul, 108(7), 1036 - 41
Immune responses of adenoidal lymphocytes specific to Haemophilus influenzae in the nasopharynx; Sakamoto N et al.; OBJECTIVES: Investigate immune responses of adenoidal lymphocytes against outer-membrane protein P6 purified from nontypeable Haemophilus influenzae (HI) . Clarify the role of adenoids in regulating the colonization of HI in the nasopharynx . STUDY DESIGN: Microbiological and immunological examinations of adenoids obtained from 21 children, 15 boys and five girls, from 1 to 13 years of age (median, 5 y), suffering from adenoidal hypertrophy complicated by otitis media with effusion (OME) . METHODS: The incidence of HI in adenoids was compared with the number of P6-specific immunoglobulin (Ig) A-secreting cells in adenoids, determined by enzyme-linked immunoassay . RESULTS: Quantitative culture assay showed significant correlation between the numbers of HI in adenoids and those in nasopharyngeal secretions (NS) . In children aged 5 years and younger, the numbers of P6-specific IgA-secreting cells in adenoids were significantly correlated with IgA antibody titers in NS (r = 0.68, P < .05) . The numbers of P6-specific IgG- and IgA-secreting cells were lower in children aged 6 years and older than in children aged 5 years and younger . Furthermore, the number of P6-specific IgA-secreting cells was significantly increased in HI-negative subjects when compared with HI-positive subjects (P < .05) . CONCLUSIONS: Adenoids play an important role as an effector site of the mucosal immune system in the upper respiratory tract . IgA immune responses in adenoids are responsible for the clearance of HI from the nasopharynx.

Curr Microbiol, 1998 Aug, 37(2), 123 - 6
Genetic transformation in Haemophilus parainfluenzae clinical isolates; Gromkova RC et al.; Haemophilus parainfluenzae isolates recovered from patients with respiratory diseases were studied for their ability to undergo genetic transformation by isogenic DNA . Two chromosomal markers, streptomycin resistance and nalidixic acid resistance, were tested for transformation efficiencies in H . parainfluenzae recipients from three biotypes . Most efficient in transformation was biotype II, followed by biotype I, while biotype III was nontransformable . Lack of transformation was not owing to poor donor activity of DNA, but to inability of the cells to develop competence . Strains that formed clumps in liquid media were nontransformable . Since the transformable biotype II is one of the prevalent biotypes world wide, one can speculate that DNA transformation probably plays a major role in the spread of drug resistance in H . parainfluenzae.

Arch Dis Child, 1998 May, 78(5), 453 - 6
Randomised controlled trial of sucrose by mouth for the relief of infant crying after immunisation; Lewindon PJ et al.; OBJECTIVES: To evaluate the effect of sucrose solution given by mouth on infant crying times and measures of distress in the immunisation clinic . DESIGN: Randomised, double blind, placebo controlled trial of sucrose solution 75% wt/vol v sterile water as a control . SETTING: The immunisation clinic of the Women's and Children's Hospital, Adelaide . PATIENTS: A total of 107 healthy infants attending for 2, 4, or 6 month immunisations with polio by mouth (Sabin), intramuscular diphtheria, tetanus, and pertussis (DTP), and intramuscular Haemophilus influenzae type b were randomised to receive 2 ml 75% sucrose solution or sterile water by mouth before the two injections . METHODS: The duration of infant crying was recorded during and immediately after two intramuscular immunisations and infant distress was assessed by a visual analogue scale (Oucher scores) independently by a nurse and a parent . RESULTS: The administration of 2 ml 75% sucrose solution by mouth reduced the infant crying time and Oucher distress scores after immunisation with DTP/H influenzae type b . CONCLUSIONS: Infant immunisation by intramuscular injection is a distressing procedure for infants and parents . Sucrose solution at a high concentration reduces infant distress and is safe and clinically useful in this setting.

Ann Otol Rhinol Laryngol, 1998 Jun, 107(6), 508 - 13
Comparative evaluation of culture and PCR for the detection and determination of persistence of bacterial strains and DNAs in the Chinchilla laniger model of otitis media; Aul JJ et al.; This study was designed to determine the persistence of culturable bacteria versus DNA in the presence of a middle ear effusion in a chinchilla model of otitis media . Cohorts of animals were either infected with an ampicillin-resistant Haemophilus influenzae strain or injected with a tripartite inoculum consisting of freeze-thawed Streptococcus pneumoniae; pasteurized Moraxella catarrhalis; and DNA from H influenzae . The H influenzae-infected animals displayed culture positivity and polymerase chain reaction positivity through day 35 . In the chinchillas infected with the low-copy number inocula of S pneumoniae, DNA was not detectable after day 1 from the co-inoculated pasteurized M catarrhalis bacteria or the purified H influenzae DNA; however, amplifiable DNA from the live low-copy number bacteria persisted through day 21 even though they were not culture-positive past day 3 . These results demonstrate that DNA, and DNA from intact but nonviable bacteria, does not persist in an amplifiable form for more than a day in the presence of an effusion; however, live bacteria, while not culturable, persist in a viable state for weeks.

Pediatr Infect Dis J, 1998 Jun, 17(6), 463 - 9
Resistance pattern of middle ear fluid isolates in acute otitis media recently treated with antibiotics; Leibovitz E et al.; BACKGROUND: Little information is available about the effect of antibiotic treatment on the prevalence and MIC of the subsequently isolated pathogens in cases of acute otitis media (AOM) failing a course of antibiotic therapy . This information is important, particularly regarding the effectiveness of the oral antibiotics used in children failing initial therapy . PATIENTS AND METHODS: One hundred eighty-one children with culture-positive AOM were prospectively studied between October, 1995, and July, 1996 . Sixty-three (35%) patients received various antibiotics for variable periods during the 14 days preceding enrollment . RESULTS: A total of 94 Streptococcus pneumoniae (Pnc) and 113 Haemophilus influenzae (Hi) were isolated . Thirty-eight Pnc and 35 Hi were isolated in the 63 patients with recently treated AOM . Pnc as a single isolate was more prevalent in patients recently treated with antibiotics (27 of 63, 43%) than among those not recently treated (32 of 118, 27%, P = 0.047) . The MIC50 values of penicillin, cefaclor and cefuroxime axetil for Pnc were significantly higher in the pneumococci isolated from patients recently treated than among those isolated from patients not recently treated with antibiotics (0.38, 3 and 0.75 microg/ml vs . 0.094, 0.38 and 0.12 microg/ml, respectively) . Seventy-nine percent of Pnc isolates in the recently treated group had MIC for penicillin of >0.1 microg/ml vs . only 47% in those not recently treated (P < 0.05) . The respective figures for MIC >0.5 microg/ml of cefaclor were 79% vs . 41% for the recently treated and not recently treated groups (P < 0.001); cefuroxime MIC >0.5 microg/ml was found in 61 and 25%, respectively (P = 0.001) . CONCLUSIONS: Pneumococcus is more prevalent in AOM after a recent antibiotic treatment, and the MIC of the commonly used beta-lactam drugs for Pnc is considerably higher in this setting . In view of our data, the use of oral cephalosporins like cefaclor or cefuroxime as second line drugs in the treatment of unresponsive AOM, particularly in regions where resistant PNC is prevalent, should be reconsidered.

Eur J Biochem, 1998 Apr 15, 253(2), 507 - 16
Structural analysis of the phase-variable lipooligosaccharide from Haemophilus somnus strain 738; Cox AD et al.; The structure of the phase variable lipooligosaccharide (LOS) from Haemophilus somnus strain 738 was elucidated . The LOS was subjected to a variety of degradative procedures . The structures of the purified products were established by monosaccharide and methylation analyses, NMR spectroscopy and mass spectrometry . The following structures for the two major components were determined on the basis of the combined data from these experiments . {structure in text} . In the structures Kdo is 3-deoxy-D-manno-octulosonic acid, PEtn is phosphoethanolamine, PCho is phosphocholine, Hep is L-glycero-D-manno-heptose, and the remaining glucose units have the D configuration . The elucidation of these structures has increased our understanding of the relationship between the phase-variable LOS and the pathogenic potential of this organism.

J Chromatogr B Biomed Sci Appl, 1998 May 8, 709(1), 97 - 104
Determination of quinolone antibiotics in growth media by reversed-phase high-performance liquid chromatography; Wright DH et al.; A simple, accurate, precise, and versatile high-performance liquid chromatographic (HPLC) method was developed and validated for the determination of three quinolone antibodies in Mueller-Hinton broth . The fluoroquinolone agents studied were ciprofloxacin, ofloxacin, and sparfloxacin; other quinolone agents have been identified using this method but not validated in this matrix (levofloxacin, clinafloxacin, temafloxacin, and trovafloxacin) . In addition, several other biological growth mediums have been investigated (human serum, human urine, Todd-Hewitt growth media, Ensure enteral feeding solution, and Haemophilus growth media) . This method uses UV detection (280 nm), a simple, one-step protein precipitation extraction, and separation using a C18 column with an isocratic, ion-pairing mobile phase . An appropriate internal standard was obtained by using another quinolone antibiotic of differing retention time . The calibration curves were linear (r2> or =0.999) over a concentration range of 0.0625-20.0 microg/ml with a lower limit of quantification of 0.1 microg/ml . The intra-day and inter-day coefficients of variation were less than 15%.

Novartis Found Symp, 1998, 213, 36 - 52; discussion 52-5
Macromolecular structure and self-assembly; Henderson R; The output from the molecular biology revolution has grown steadily and logarithmically from the first protein sequence, insulin (Ryle AP et al 1955 Biochem J 60:541-556), the first three-dimensional atomic structure of a macromolecule, myoglobin (Kendrew JC et al 1960 Nature 185:422-427), the first DNA gene sequence, phi X174 gene J (Sanger F et al 1977 Nature 265:687-695) and the first genome sequence for a free-living organism, Haemophilus influenzae (Fleischmann RD et al 1995 Science 269:496-512) to the current situation where the output rate is close to one new gene sequence every few minutes, several new three-dimensional structures a day and a new (bacterial) genome completed every few months . Those working in this field must readjust their horizons to this changing situation every year or two . In the area of three-dimensional structure of macromolecules and macromolecular assemblies, the methods of X-ray crystallography, nuclear magnetic resonance and electron microscopy have combined to produce powerful insights into how these molecular machines work . In this paper, I present three examples of molecular machines whose structure tells us a lot about how they work . These are the light-driven proton pump bacteriorhodopsin, the ATP synthetase molecule which contains a tiny motor and generator, and the flagellar rotary motor which provides the thrust to power physical movement of the bacterial cell . The structure itself in three-dimensional detail is thus often seen to provide the most important single insight into how things work, reducing biology to chemistry and physics . The reductionist approach in this field seems to be limited only by the accuracy by which it is possible to describe inter- and intra-molecular interactions in terms of hydrogen bonds, van der Waals interactions and electrostatic forces . At present, there is no fundamental limit in sight.

J Infect Dis, 1998 Jul, 178(1), 191 - 9
Evaluation of an isogenic hemolysin-deficient mutant in the human model of Haemophilus ducreyi infection; Palmer KL et al.; Haemophilus ducreyi causes the genital ulcerative disease chancroid . One putative virulence factor of H . ducreyi is a pore-forming hemolysin that displays toxicity against human fibroblasts and keratinocytes . In order to test the role of the hemolysin in pathogenesis, an isogenic hemolysin-deficient mutant was constructed, designated 35000HP-RSM1 . The lipooligosaccharide, outer membrane protein patterns, and growth attributes of 35000HP-RSM1 were identical to its parent, 35000HP . Human subjects were challenged on the upper arm with the isogenic isolates in a double-blinded, randomized, escalating dose-response study . Pustules developed at a similar rate at sites inoculated with the mutant or parent . The cellular infiltrate and bacterial load in lesions were also similar . These results indicate the hemolysin does not play a role in pustule formation . Due to the limitations of this model, the role of the hemolysin at later stages of infection could not be determined.

J Infect Dis, 1998 Jul, 178(1), 243 - 6
Molecular methods for the diagnosis of genital ulcer disease in a sexually transmitted disease clinic population in northern Thailand: predominance of herpes simplex virus infection; Beyrer C et al.; A multiplex polymerase chain reaction (M-PCR) assay that simultaneously detects the three major causes of genital ulcer disease (GUD), Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus, was used to evaluate swab specimens for 38 sequential patients with GUD at a Thai sexually transmitted disease clinic . Subjects received clinical diagnoses and syndromic treatment . Swab specimens for H . ducreyi cultures and M-PCR were obtained . No H . ducreyi cultures were positive . Of 38 M-PCR specimens, 31 (81.6%) were positive for HSV, 1 (2.3%) for both HSV and T . pallidum, and none for H . ducreyi or T . pallidum alone; 6 (15.8%) were negative for all 3 pathogens . Clinical diagnoses corresponded poorly to M-PCR findings; none of 5 suspected cases of chancroid were positive by M-PCR and none of 1 for syphilis, but 21 of 24 suspected herpes lesions were confirmed by M-PCR . Human immunodeficiency virus infection status was known for 24 of 38 subjects; 11 (45.8%) were seropositive, and all 11 had HSV by M-PCR . HSV appeared to be the most common pathogen overall.

Arch Med Res, 1998 Summer, 29(2), 133 - 6
Biotypes and serotypes of Haemophilus influenzae of clinical isolates from Mexican children; Sosa-Iglesias EG et al.; BACKGROUND: Infectious diseases caused by H . influenzae type b are considered preventable through vaccination with Hib conjugate vaccines . Some countries which follow Hib vaccination programs are close to eradication of the disease . In Mexico in particular, little epidemiological information is available . METHODS: In this study, 90 clinical strains of H . influenzae were obtained from Mexican children who were treated in four pediatric hospitals in Puebla City, and were diagnosed with invasive or localized infectious diseases . The strains were identified by standard bacteriological methods . Biotyping was done by Kilian criteria and serotyping by coagglutination . RESULTS: H . influenzae infections were found in children younger than 5 years of age, and 68.8% of the children were younger than 24 months . Sixty percent of the isolates belonged to serotype b, 31.1% were nontypeable, and 7.7% were considered non-type b . Serotype b was the most frequent isolate associated with invasive infectious diseases; however, nontypeable strains were isolated more frequently from children with otitis, sinusitis, conjunctivitis, and bronchial secretion . Non-type b serotypes were isolated from invasive and non-invasive infections in few cases . Biotypes I and IV were the most frequent isolates of H . influenzae . CONCLUSIONS: This study emphasizes the urgent need for an Hib-conjugated vaccine to achieve immunization in a pediatric population.

J Allergy Clin Immunol, 1998 Jun, 101(6 Pt 1), 726 - 31
The common cold: effects of intranasal fluticasone propionate treatment; Puhakka T et al.; OBJECTIVE: A double-blind, randomized, placebo-controlled trial was conducted to study the effect of the intranasal corticosteroid, fluticasone propionate (FP), in the naturally occurring common cold . METHODS: One hundred ninety-nine young adults received high-dose FP (200 microg four times daily) or placebo beginning 24 to 48 hours after onset of the common cold for 6 days . All symptoms were recorded on diary cards on days 1 to 20, and clinical examinations were carried out on days 1, 7, and 21 . Nasopharyngeal aspirates were collected on days 1 and 7 for detection of rhinoviruses (found in 105 subjects) and Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis (found in 52 subjects) in the nasopharynx . RESULTS: In general, FP treatment had no clinically recognizable effects on the symptoms of the common cold, although it significantly reduced nasal congestion and cough on some study days . After treatment, rhinoviruses were cultured more often in the FP treatment group (37% vs 14%, p < 0.001), but this had no effect on the symptoms of common cold . FP treatment produced no changes in the colonization of pathogenic bacteria in the nasopharynx . Some symptoms of common cold were significantly more severe during days 1 to 10 (p < 0.05) in subjects found to have positive cultures for S . pneumoniae, H . influenzae, or M . catarrhalis in the nasopharynx on day 1 (n = 33) . CONCLUSION: FP treatment does not have any marked effects on the symptoms of the common cold . FP treatment induced prolonged shedding of viable rhinoviruses . Some symptoms of the common cold were significantly more severe in subjects with pathogenic bacteria in the nasopharynx.

J Chromatogr A, 1998 May 15, 806(2), 279 - 91
Enrichment and purification of proteins of Haemophilus influenzae by chromatofocusing; Fountoulakis M et al.; Haemophilus influenzae is a bacterium of pharmaceutical interest of which the entire genome has been sequenced . Identification of low-abundance proteins in a two-dimensional map is important for the detection of new drug targets . We applied chromatography on Polybuffer Exchanger (chromatofocusing) in order to fractionate and enrich H . influenzae proteins, possibly low-copy-number gene products, from larger volumes . Two proteins, major ferric iron-binding protein (HI0097) and 5'-nucleotidase (HI0206) were obtained in pure form and hypothetical protein HI0052 was purified to near homogeneity by this single purification step . Four other proteins, aspartate ammonia lyase (HI0534), peptidase D (HI0675), elongation factor Ts (HI0914) and 5-methyltetrahydropteroyltriglutamate methyltransferase (HI1702), were strongly enriched so that chromatography on Polybuffer Exchanger can be used as an initial step for their isolation . Approximately 125 proteins were identified in the fractions collected from the column . Seventy of these were for the first time identified after chromatography on Polybuffer Exchanger . The proteins enriched by the chromatofocusing step include both low-abundance as well as high-copy-number gene products . They do not belong to a single protein class and the majority of them are enzymes with various functions . The results include a list and a two-dimensional map of the proteins enriched by chromatofocusing . They may be useful in the search of drug targets and in the design of purification protocols for the isolation of homologous proteins from related microorganisms.

East Afr Med J, 1998 Feb, 75(2), 73 - 6
Bacterial meningitis in children admitted in hospitals within Nairobi; Mirza NB et al.; Four hundred and ninety nine children (aged between one month and five years) admitted with clinical features of meningitis were recruited in cross-sectional survey of bacterial meningitis in hospitals within Nairobi . Lumbar punctures were done on all of them and the cerebrospinal fluid (CSF) analysed bacteriologically and serologically for the common causative organisms . Two hundred and fifty (50.1%) cases were diagnosed clinically as having meningitis . Of these, 132 (52.8%) had turbid CSF specimens, while 118 (47.2%) were clear . When turbid CSF specimens were cultured, 83 (62.8%) yielded three common bacterial micro-organisms namely; Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae in that order of frequency . The implications of these findings in paediatric meningitis together with the drug sensitivity patterns is presented and discussed.

East Afr Med J, 1998 Mar, 75(3), 162 - 5
In-vitro activity of piperacillin and tazobactam combination against clinically significant bacteria; Obi CL et al.; The in-vitro activity of piperacillin/tazobactum which is not among the routinely tested antibiotic at the Public Health Bacteriology Laboratory, Parirenyatwa Hospital, Harare, Zimbabwe was evaluated for its activity against bacterial pathogens using the Kirby-Bauer disk diffusion method . Piperacillin/tazobactum showed superior in-vitro activity against both gram positive and gram negative bacteria when compared with routinely tested antibiotics such as gentamicin, erythromycin, tetracycline, penicillin, chloramphenicol, fusidic acid and clindamycin and the difference was statistically significant (p < 0.05) . Ciprofloxacin showed in-vitro activity comparable to that of tazobactam/piperacillin . Specifically, 96% of gram positive isolates (comprising Streptococcus pyogenes, Staphylococcus aureus, coagulase negative staphylococci and Streptococcus pneumoniae were sensitive to piperacillin/tazobactam . For gram negative organisms, 98% of Haemophilus influenzae Shigella spp, Klebsiella spp were also sensitive to the combination . The broad spectrum of activity of piperacillin/tazobactam shows that the potential of the drug combination for the treatment of infections caused by diverse microorganisms should not be underestimated . We recommend its inclusion in routine antibiotic sensitivity testing in our hospital.

FEMS Microbiol Rev, 1998 Apr, 22(1), 45 - 59
Adhesin-receptor interactions in Pasteurellaceae; Jacques M et al.; The ability of bacteria to adhere to mucosal epithelium is dependent on the expression of adhesive molecules or structures, called adhesins, that allow attachment of the organisms to complementary molecules on mucosal surfaces, the receptors . Important human and animal pathogens are found among the Pasteurellaceae family which includes Haemophilus, Actinobacillus, and Pasteurella organisms . The purpose of this paper is to review the adhesin-receptor systems found in Pasteurellaceae, with an emphasis on recent developments in this specific area . Most of these organisms can employ multiple molecular mechanisms of adherence (or multiple adhesins) to initiate infection . Indeed, a wide variety of adhesins are expressed by members of the Pasteurellaceae, and different proteins (e.g . fimbriae, fibrils, outer membrane proteins) as well as polysaccharides (lipooligosaccharides, lipopolysaccharides, capsular polysaccharides) were clearly shown to play an important role in adherence . In many instances, these adhesins have proved to represent good vaccine candidates . Surprisingly, the receptors on host mucosal surfaces have yet been identified in very few cases.

Berl Munch Tierarztl Wochenschr, 1998 May, 111(5), 164 - 72
{Occurrence of bacterial infectious agents in pathologically/anatomically altered lungs of pigs and compilation of resistance spectra}; von Altrock A; The goal of this work was to investigate the type and etiology of bacterial porcine pneumonia by analyses of autopsy findings made in the Tierarztlichen Ambulanz Schwarzenbek, Aussenstelle der Freien Universitat Berlin, and in the Institut fur Tiergesundheit, Milchhygiene und Lebensmittelqualitat der Landwirtschaftskammer Westfalen-Lippe in Munster in the years from 1991 to 1993 . The evaluation of the results of the total 6560 autopsies (N = 6560) of pigs shows: 1 . Pneumonia as the main diagnosis was found in 24.4% (n = 1599), as the second diagnosis in 14.3% (n = 941) of the sections . 2 . Fattening pigs show signs of pneumonia (43.2% (n = 1096) vs . 27.8% (n = 706); N = 2540) more frequently than younger pigs . 3.The most frequently isolated etiologic agents from lung specimens (N = 2337) were Pasteurella multocida (49.3%; n = 1152), Actinobacillus pleuropneumoniae (5.4%; n = 125) and Bordetella bronchiseptica (5.3%; n = 124) . 4 . With increasing age of the isolation rate of Pasteurella multocida (piglets {N = 210}: 21.4%, n = 45; fattening pigs {N = 652}: 61.8%, n = 403) and Actinobacillus pleuropneumoniae (piglets: 1.4%, n = 3; fattening pigs: 7.1%, n = 46) increased while Bordetella bronchiseptica (piglets: 10.0%, n = 21; fattening pigs: 1.1%, n = 7) and Haemophilus parasuis (piglets: 3.8%, n = 8; fattening pigs: 0%, n = 0) were isolated at decreasing rates . 5 . Most cultures of the lung samples (N = 2337) showed multiple infections (1087 = 54.2%) . 6 . The highest rate of single bacterial isolates was found for Pasteurella multocida (40.9%, n = 471, N = 1152) in relation to Haemophilus parasuis (30.9%, n = 11, N = 36), Actinobacillus pleuropneumoniae (24.0%, n = 30, N = 125), and Bordetella bronchiseptica (20.2%, n = 25, N = 124) . 7 . Less than 10% of the examined Pasteurella multocida, Actinobacillus pleuropneumoniae, Bordetella bronchiseptica and Haemophilus parasuis strains were resistant to tetracycline, oxytetracycline, enrofloxacin and kanamycin, but more than 55% were resistant to sulfonamides.

Vet J, 1998 May, 155(3), 251 - 5
Bovine serum transferrin concentration during acute infection with Haemophilus somnus; McNair J et al.; A novel, competitive immunoassay based on time-resolved fluorimetry was developed, and used to measure the serum concentration of bovine transferrin during acute Haemophilus somnus pneumonia . Upper and lower limits of normality were established using serum from healthy cattle (3.72-1.37 mgmL-1) . Following experimental infection with Haemophilus somnus, transferrin concentration was depressed in all calves but recovered to pre-infection levels in groups of calves which had either no lesions, or mild lesions at necropsy between 5 and 6 days after infection . In a third group, which developed extensive lesions, the transferrin concentration remained depressed . Transferrin levels remained within the normal range for all calves during the experimental period . Those calves which had low transferrin concentrations pre-infection, developed extensive lung lesions following experimental infection with Haemophilus somnus.

Biologicals, 1998 Mar, 26(1), 33 - 8
A simple and rapid method for measuring unconjugated capsular polysaccharide (PRP) of Haemophilus influenzae type b in PRP-tetanus toxoid conjugate vaccine; Guo YY et al.; The authors developed a simple and rapid method for quantitation of free capsular polysaccharide of Haemophilus influenzae type b (polyribosyl ribitol phosphate, PRP) in PRP-tetanus toxoid conjugate vaccine based on acid precipitation of tetanus toxoid (TT) . Acid hydrolysis of PRP during the assay was not detected . The conditions used in the assay did not precipitate unconjugated PRP or adipic acid dihydrazide derivatized PRP . The method was highly reliable, reproducible and sensitive . The accuracy of the assay was confirmed by spiking known amounts of unconjugated PRP to PRP-TT conjugate preparations . A PRP-TT preparation, incubated at 37 degrees C for 6 months showing most of the PRP as unconjugated (87% determined by this method), was not immunogenic in mice for the PRP component even after two injections . In contrast, the same preparation held at 4 degrees C for 20 months, showing 17% unconjugated PRP, induced IgG antibodies to PRP which were boosted after second injection . Therefore, this method is very useful to evaluate the stability of PRP-TT conjugate vaccine . The assay may be useful for characterizing other polysaccharide-protein conjugate vaccines.

Infect Immun, 1998 Jul, 66(7), 3403 - 9
Low genetic diversity of Haemophilus influenzae type b compared to nonencapsulated H . influenzae in a population in which H . influenzae is highly endemic; Smith-Vaughan HC et al.; Immunization with Haemophilus influenzae type b (Hib) conjugate polysaccharide vaccines has dramatically reduced Hib disease worldwide . As in other populations, nasopharyngeal carriage of Hib declined markedly in Aboriginal infants following vaccination, although carriage has not been entirely eliminated . In this study, we describe the genetic characteristics and the carriage dynamics of longitudinal isolates of Hib, characterized by using several typing methods . In addition, carriage rates of nonencapsulated H . influenzae (NCHi) are high, and concurrent colonization with Hib and NCHi is common; we also observed NCHi isolates which were genetically similar to Hib . There is a continuing need to promote Hib immunization and monitor H . influenzae carriage in populations in which the organism is highly endemic, not least because of the possibility of genetic exchange between Hib and NCHi strains in such populations.

Infect Immun, 1998 Jul, 66(7), 3349 - 54
A 20-kilodalton N-terminal fragment of the D15 protein contains a protective epitope(s) against Haemophilus influenzae type a and type b; Yang Y et al.; A conserved 80-kDa minor outer membrane protein, D15, of Haemophilus influenzae has been shown to be a protective antigen in laboratory animals against H . influenzae type a (Hia) or type b (Hib) infection . To localize the protective B-cell epitope(s) within the D15 protein and to further explore the possibility of using synthetic peptides as vaccine antigens, a 20-kDa N-terminal fragment of D15 protein (truncated D15 {tD15}) was expressed as a fusion protein with glutathione S-transferase in Escherichia coli . The tD15 moiety was cleaved from glutathione S-transferase by using thrombin and purified to homogeneity . The purified soluble tD15 appeared to contain immunodominant protective epitope(s) against Hia and Hib, since rabbit antisera directed against tD15 were capable of protecting infant rats from Hia or Hib bacteremia . The ease of purification of soluble tD15, therefore, makes it a better candidate antigen than the full-length recombinant D15 which is produced as inclusion bodies in E . coli . Furthermore, both the purified tD15 fragment and a mixture of tD15-derived peptides spanning amino acid residues 93 to 209 of the mature D15 protein were capable of inhibiting the protection against Hib conferred on infant rats by rabbit anti-tD15 antiserum, indicating that the protective epitopes of D15 may not be conformational . However, the administration of pooled rabbit immune sera raised against the same panel of peptides failed to protect infant rats from Hib infection.

APMIS, 1998 Apr, 106(4), 434 - 40
Clinical microbiology laboratories do not always detect resistance of Haemophilus influenzae with disk or tablet diffusion methods . Finnish Study Group for Antimicrobial Resistance (FiRe); Manninen R et al.; The performance of disk diffusion testing of Haemophilus influenzae was evaluated in 20 laboratories . Thirteen disk-medium-breakpoint-inoculum modifications were used in Finnish clinical microbiology laboratories . The performance of various methods was evaluated by testing a susceptible control strain and one with non-beta-lactamase-mediated ampicillin resistance 10 times in 16 laboratories . Gaps in millimeters were measured between these two groups of results . The strains were separated by a gap of at least 5 mm in 8/16 laboratories testing ampicillin, in 7/15 laboratories testing cefaclor, in 5/ 16 laboratories testing cefuroxime, and in 15/16 laboratories testing trimethoprim-sulfa . Detection of ampicillin resistance was better with 2.5 microg tablets than with 10 microg disks or 33 microg tablets . For MIC-determinations, 785 isolates and their disk diffusion results were collected . None of the 12 clinical isolates with non-beta-lactamase-mediated ampicillin resistance was detected as resistant in the participating laboratories . The ampicillin and cefaclor results of the isolates were no better even when a laboratory was able to separate the control strains . Cefaclor results were unreliable because of poor disk diffusion-MIC correspondence and incoherent breakpoint references . Interlaboratory variation of the zone diameters caused false intermediate results of cefuroxime-susceptible strains . When ampicillin, cefaclor and cefuroxime were tested, the discrimination of laboratories using disks and tablets was equal, whereas the laboratories using paper disks were better able to detect trimethoprim-sulfa resistance.

Ann Dermatol Venereol, 1996, 123(12), 827 - 8
{Type B Haemophilus influenzae cellulitis in an immunocompetent adult}; Tanasescu S et al.; INTRODUCTION: Only a few cases of Haemophilus influenzae type B cellulitis have been reported in adult patients . They generally involve immunocompromised patients, and are located in the cervico-facial areas . CASE-REPORT: We report a 43 year-old immunocompetent patient who presented a cellulitis of the leg . No cutaneous or upper respiratory pathways entry portal was found . Abcedation of cutaneous lesions allowed the isolation of numerous colonies of Haemophilus influenzae type B from a subcutaneous fluid aspirate . COMMENTS: The unusual site of the infection, the age and the immunocompetent status of the patient, the lack of initial infectious localisation and the slow healing of lesions despite appropriated antibiotic therapy, are of particular interest.

Lancet, 1998 Jun 13, 351(9118), 1778 - 81
Effect of immunosuppression after cardiac transplantation in early childhood on antibody response to polysaccharide antigen; Gennery AR et al.; BACKGROUND: Three children who had cardiac transplantation before age 4 years later presented with recurrent sinopulmonary infection caused by organisms including Streptococcus pneumoniae, in which capsular polysaccharide plays an important part, one developed bronchiectasis . We therefore studied responses to polysaccharide antigen after immunosuppression started in early childhood . METHODS: Antibodies against pneumococcal and haemophilus polysaccharides, and total IgG, IgG1, IgG2, and IgA concentrations were measured in 33 cardiac-transplant recipients transplanted before the age 4 years (group 1) and after that age (group 2) . Patients with low pneumococcal and haemophilus antibody concentrations were immunised with 23 polyvalent pneumococcal and tetanus-haemophilus conjugate vaccines and antibody responses were measured . FINDINGS: Five patients from group 1 and seven from group 2 were transplanted for congenital heart disease and ten patients in each group had heart transplants because of cardiomyopathy; none were asplenic . Group 1 (16 patients) were aged 2-10 years when investigated, group 2 (17 patients), were 6-16 years . Four of 16 patients in group 1 responded to pneumococcal polysaccharide vaccine compared with 14 of 17 in group 2 (p=0.0016) . This difference remained when those in group 1, aged less than 4 years at investigation, were excluded (p=0.0060) . Response to haemophilus-conjugate vaccine was similar in both groups (14 of 16 vs 14 of 17, p=1.0) . Significantly more patients who failed to respond to pneumococcal vaccine had low IgG2 concentrations (p=0.0269) . INTERPRETATION: Children who had a transplantation and immunosuppression in early childhood before they had developed antibody responses to pneumococcal polysaccharide, still failed to show a response when older-ie, when such responses are the norm . Ongoing immunosuppression prevents the maturation of antipolysaccharide responses leaving children susceptible to severe and recurrent damaging infection.

Diagn Microbiol Infect Dis, 1998 Jun, 31(2), 349 - 53
Comparative antimicrobial activity and kill-curve investigations of novel ketolide antimicrobial agents (HMR 3004 and HMR 3647) tested against Haemophilus influenzae and Moraxella catarrhalis strains; Biedenbach DJ et al.; The activity of two ketolide compounds, HMR 3004 and 3647, were compared to those of five macrolides, quinupristin/dalfopristin, ciprofloxacin, and ampicillin . The rate of killing for the ketolides was also assessed against Haemophilus influenzae and Moraxella catarrhalis . One hundred H . influenzae and 148 M . catarrhalis isolates were tested using broth microdilution and appropriate growth media . The killing rates of HMR 3004 and 3647 were analyzed using the time-kill method against five strains from each of the two species . Against H . influenzae, the activity of the ketolides (MIC90, 2 or 4 microg/mL) resembled that of azithromycin and quinupristin/dalfopristin and was more active than any tested macrolide . Against M . catarrhalis, HMR 3004 and 3647 were equally potent as azithromycin and clarithromycin (MIC50, 0.06 microg/mL and MIC90, 0.12 microg/mL) and more potent than all other macrolides or quinupristin/dalfopristin . Time-kill kinetic studies revealed that like the macrolide compounds, the ketolides are bacteristatic at or near the MIC for both H . influenzae and M . catarrhalis . This activity can be increased to a bactericidal level if the concentration is increased four- or eightfold the MIC for H . influenzae . In conclusion, HMR 3004 and 3647 have bacteristatic activity against tested respiratory pathogens and may prove to have an important role against macrolide-resistant isolates.

Biotechnology (N Y), 1995 Feb, 13(2), 170 - 4
Recent advances in the large scale fermentation of Neisseria meningitidis group B for the production of an outer membrane protein complex; Fu J et al.; The Outer Membrane Protein Complex (OMPC) of the bacterium Neisseria meningitidis group B has been used successfully as a protein carrier in a Haemophilus influenza type b (Hib) polysaccharide conjugate vaccine and a Streptococcus pneumoniae (Pn) polysaccharide conjugate vaccine to elicit antipolysaccharide immune responses in young infants . The OMPC carrier is derived by detergent extraction of whole cells and, thus, the consistent generation of suitable biomass is central to an effective production process . Therefore, we have developed a large-scale, high-cell density (5 g/L dry cell weight) fermentation process for the cultivation of N . meningitidis B11 . Since current requirements for the production of human biologics mandate strict control of all aspects of the manufacturing process, several key features of the process, including a chemically defined medium and a rational event-based harvest criterion, support current good manufacturing practice (cGMP) and increased productivity.

Jpn J Antibiot, 1997 Mar, 50(3), 272 - 97
{Clinical study on azithromycin in 10% fine granules and 100mg capsules in the field of pediatrics}; Motohiro T et al.; Azithromycin (AZM), a new oral macrolide antibiotic, in 10% fine granules or 100 mg capsules was given to pediatric patients to treat various infections . The following results were obtained in our studies of AZM for its antibacterial activities against clinical isolates, its pharmacokinetics, its efficacy, and its safety . 1 . MICs of AZM, erythromycin (EM) and clarithromycin (CAM) were determined against a total of 57 strains all at 10(6) cfu/ml . Among Gram-positive cocci, MICs of AZM ranged from 0.78 to > 100 micrograms/ml against Staphylococcus aureus (20 strains), from 0.05 to 0.1 microgram/ml against Streptococcus pyogenes (11 strains), and from 0.0125 to 3.13 micrograms/ml against Streptococcus pneumoniae (10 strains) . These MICs were similar to those of the other macrolides . Among Gram-negative bacilli, MICs of AZM were 0.05 micrograms/ml against Moraxella subgenus Branhamella catarrhalis (1 strain), from 0.78 to 3.13 micrograms/ml against Haemophilus influenzae (9 strains), 0.78 micrograms/ml against Haemophilus parainfluenzae (1 strain) and 6.25 micrograms/ml against salmonella sp . (1 strain) . These values were similar to or lower than those of the other macrolides . Against Mycoplasma pneumoniae, MICs of AZM were < or = 0.0008 micrograms/ml in three strains . One strain of M . pneumoniae showed tolerance to AZM at MIC 25 micrograms/ml . The other agents exhibited higher MIC than AZM against this organism . 2 . Plasma samples were collected from five patients receiving fine granules and four patients receiving capsules for drug level determination . The patients received AZM at 10.0 approximately 16.3 mg/kg body weight once daily for 3 days . Drug concentrations in plasma at two hours after Day 3 dosing were in a range between 0.02 and 0.19 micrograms/ml for fine granules and were in a range between 0.11 and 0.42 micrograms/ml for capsules . 3 . Urine samples were collected from four patients receiving fine granules and four patients receiving capsules . Drug levels were determined to be 3 micrograms/ml at post-treatment 48 hours for fine granules and post-treatment 72 hours for capsules . Urinary excretion rates of AZM in three patients on capsules lied in a range between 4.69 and 10.17% . 4 . Effectiveness of AZM in fine granules was evaluated in 128 patients having a total of 19 different infections . AZM was rated "excellent" in 51 patients, "good" in 63, "fair" in 8, "poor" in 6, resulting in an efficacy rate of 89.1% . Effectiveness of AZM in capsular form was evaluated in 23 patients with five different infections . AZM was found "excellent" in 13 patients and "good" in 10, resulting in an efficacy rate of 100% . 5 . AZM in fine granules eradicated 45 strains of 54 in 8 different bacteria . AZM in capsules eradicated 9 strains of 10 strains in 6 different bacteria . 6 . As for adverse reactions, one patient complained of eruption, one vomiting, one loose stool, five diarrhea, when administered with fine granular form of AZM . One patient on AZM capsules experienced urticaria and vomiting . 7 . As for abnormal laboratory changes, three patients were found with decreased WBC, seven with increased eosinophil, two with increased GOT and GPT, one with increased GPT . They were all on fine granular form of AZM . As far as abnormalities found in patients administered with AZM in capsular form, two showed decreased WBC, one decreased WBC along with increased eosinophil, and three increased eosinophil.

Sex Transm Infect, 1998 Apr, 74(2), 95 - 100
Oral sex and transmission of non-viral STIs; Edwards S et al.; OBJECTIVES: To review the literature on the role of oral sex in the transmission of non-viral sexually transmitted infections (STIs) . METHOD: A Medline search was performed using the keywords oro-genital sex, and those specific to each infection . Further references were then taken from each article read . CONCLUSIONS: Oral sex is a common sexual practice between both heterosexual and homosexual couples . Oro-genital sex is implicated as a route of transmission for gonorrhoea, syphilis, Chlamydia trachomatis, chancroid, and Neisseria meningitidis . Other respiratory organisms such as streptococci, Haemophilus influenzae, and Mycoplasma pneumoniae could also be transmitted by this route . Fellatio confers risk for acquisition of infection by the oral partner . Cunnilingus appears to predispose to recurrent vaginal candidiasis although the mechanism for this is unclear, while a link between oro-genital sex and bacterial vaginosis is currently being studied . Oro-anal sex is implicated in the transmission of various enteric infections . In view of the increased practice of oral sex this has become a more important potential route of transmission for oral, respiratory, and genital pathogens.

Sex Transm Infect, 1998 Feb, 74(1), 63 - 5
Polymerase chain reaction detection of Haemophilus ducreyi DNA; Roesel DJ et al.; OBJECTIVES: To develop a polymerase chain reaction (PCR) method to detect Haemophilus ducreyi DNA in cultured isolates and clinical material . METHODS: Primers specific to the H ducreyi 16s rRNA gene were synthesised . PCR conditions were optimised and products were verified by restriction endonuclease digestion and agarose gel electrophoresis . RESULTS: The method was able to detect all 28 H ducreyi strains tested; specificity was demonstrated using lysates of 12 related organisms . Applied to clinical samples from genital ulcer swabs obtained in Harare, Zimbabwe, H ducreyi DNA was detected in repeated assays in 35 clinical samples . CONCLUSION: PCR amplification using primers from the 16s rRNA gene may be a useful alternative to culture for the detection of H ducreyi and the diagnosis of chancroid.

Microb Pathog, 1998 Jun, 24(6), 351 - 9
Apoptosis: a possible tactic of Haemophilus somnus for evasion of killing by bovine neutrophils?
Yang YF, Sylte MJ, Czuprynski CJ.
Haemophilus somnus is an important veterinary pathogen that causes respiratory disease, arthritis, septicaemia and abortion in cattle and sheep . In the present study we investigated the possibility that H . somnus resists killing by bovine neutrophils, by causing the latter to undergo morphological changes consistent with apoptosis . Both serum-sensitive and serum-resistant strains of H . somnus enhanced bovine neutrophil chromatin condensation and shape change (i.e . zeiosis) in vitro, suggesting that the cells were undergoing apoptosis . Heat-killed or formalin-killed H . somnus had less effect than viable H . somnus . Chromatin margination of neutrophils was greater whenH . somnus was opsonized with adult bovine serum, which facilitates phagocytosis of the bacteria . H . somnus culture filtrates did not cause bovine neutrophil chromatin condensation . These findings suggest that direct contact with H . somnus is required for the maximal effect on bovine neutrophils . Apoptosis was confirmed by flow cytometry, using propidium iodide staining to detect DNA fragmentation . These findings suggest that H . somnus can evade killing by bovine neutrophils, in part, by inducing these cells to undergo apoptosis .

Med J Aust, 1998 May 18, 168(10), 491 - 4
Vaccinating children with a history of serious reactions after vaccination or of egg allergy; Andrews RM et al.; OBJECTIVE: To describe the results of vaccinating children with a history of serious adverse reactions after vaccination or of egg allergy at a special clinic established for that purpose . DESIGN: Retrospective case series . PATIENTS: Children who attended the clinic between 1 August 1994 and 31 July 1996 after being referred by vaccine providers . SETTING: A clinic conducted in the Emergency Department of The Canberra Hospital, Australian Capital Territory . MAIN OUTCOME MEASURES: Reasons for referral; vaccinations given; and subsequent adverse vaccination events . RESULTS: 91 children received 155 vaccinations at the clinic, and only one serious event--a hypotonic/hyporesponsive episode (HHE) after diphtheria-tetanus-whole-cell pertussis (DTPw), oral polio and Haemophilus influenzae type b vaccination--was subsequently reported; this child recovered spontaneously . Fifty-three children referred because of a previous serious adverse vaccination event were revaccinated at the clinic with whole-cell pertussis vaccine (47), combined diphtheria and tetanus vaccine (4), tetanus toxoid (1), and typhoid vaccine (1) . Three children (referred because of previous meningitis, subdural haemorrhage or parental suspicion of allergy to DTPw) received their first dose of pertussis vaccine at the clinic . The remaining 35 children had a history of egg allergy and were given measles-mumps-rubella vaccine . CONCLUSIONS: We successfully vaccinated children with histories of serious reactions to vaccination, including HHEs, convulsions, apnoea, high temperatures and persistent screaming, as well as those with egg allergy . We believe special clinics can improve vaccination coverage.

Med J Aust, 1998 May 18, 168(10), 487 - 90
Home vaccination for children behind in their immunisation schedule: a randomised controlled trial; Bond LM et al.; OBJECTIVE: To ascertain the effectiveness of a home vaccination service for children behind in their vaccination schedule . DESIGN: Randomised controlled trial of nurse-administered vaccination at home . Children were allocated at random to the intervention or the control group before any contact with the parents was made . SETTING: 10 council areas in north-west metropolitan Melbourne defined by 56 postcode zones . Six-week intervention period from November 1996 . PARTICIPANTS: 405 children--all those in the study area (n = 2610) 90 days late (age 9 months) for their third diphtheria-tetanus-pertussis/poliomyelitis/Haemophilus influenzae type B (DTP/OPV/Hib) vaccination, or 120 days late (age 16 months) for their measles-mumps-rubella (MMR) vaccination, according to the Australia Childhood Immunisation Register . MAIN OUTCOME MEASURES: Number of children completing DTP/OPV/Hib or MMR during the intervention period, and number up to date before intervention . RESULTS: Verification of vaccination status with the parents revealed that 123 (60%) of the children in the intervention group and 113 (56%) of those in the control group were up to date with their vaccinations, leaving a study population of 81 (intervention group) and 88 (control group) . Vaccination was achieved in 46 (57%) intervention children and 24 (27%) control children (risk ratio {RR}, 2.08; 95% CI, 1.4-3.1; P < 0.001) . For DTP/OPV/Hib, 18/32 (56%) intervention children and 12/36 (33%) control children were vaccinated, (P = 0.06) . For MMR, 28/49 (57%) and 12/52 (23%) children were vaccinated, respectively (P < 0.001) . Home vaccinations were completed with 26 families (including five siblings) . The average cost per child vaccinated as a result of the home program was $92.52 . CONCLUSION: Home vaccination for children behind in their immunisation schedule is an effective, acceptable and relatively cheap method of completing recommended vaccinations . We recommend that a home vaccination program be widely implemented and made available, particularly for disadvantaged families.

J Antimicrob Chemother, 1998 May, 41(5), 563 - 5
Antiadhesive effects of xylitol on otopathogenic bacteria; Kontiokari T et al.; The exposure of either epithelial cells or pneumococci or both to 5% xylitol reduced the adherence of pneumococci . Exposure of epithelial cells or bacteria alone to xylitol did not reduce the adherence of Haemophilus influenzae, although the exposure of both cells and bacteria to xylitol reduced the adherence significantly . The adherence of Moraxella catarrhalis remained low irrespective of the exposure.

Electrophoresis, 1998 May, 19(5), 761 - 6
Two-dimensional map of basic proteins of Haemophilus influenzae; Fountoulakis M et al.; Haemophilus influenzae is a bacterium of medical interest of which the entire genome has been sequenced . The proteome of the microorganism has been analyzed by two-dimensional gel electrophoresis, during which immobilized pH 3-10 gradient strips were used and approximately 300 proteins were identified . In order to detect additional, basic proteins, we analyzed the soluble protein fraction of H . influenzae and the proteins of fractions collected from affinity chromatography on heparin, by two-dimensional gel electrophoresis, using for the first-dimensional separation immobilized pH gradient strips comprising the pH region of 6-11 . The protein spots were analyzed by matrix-assisted laser desorption ionization-mass spectrometry . One hundred and two proteins were identified, of which 58 were identified for the first time . A large percentage of the basic proteins represent nucleic acid binding and, in particular, ribosomal proteins . The locations of the identified basic proteins of H . influenzae are indicated in a two-dimensional map.

An Esp Pediatr, 1998 Apr, 48(4), 352 - 4
{Vaccination against Haemophilus influenzae type b in the Valencia Community: efficacy and failure of vaccinations}; Morant Gimeno A et al.; OBJECTIVE: To study Haemophilus influenzae type b (Hib) conjugate vaccine effectivity and vaccine failures in the Valencian Community of Spain where vaccine can be obtained, but is not scheduled as a routine immunization . PATIENTS AND METHODS: A prospective surveillance system where pediatricians and microbiologists of all public hospitals of the Valencian Community reported cases of invasive Hib disease in children (under 15 years of age) . Vaccination status (number of doses, dates and type of vaccine) in each case was obtained . RESULTS: Of 23 cases reported from December 1, 1995 to November 30, 1996, two had received at least one dose of Hib vaccine . One was a true vaccine failure and the other an apparent vaccine failure . Estimating a vaccine coverage of 32.5% of the children less than 5 years old, the direct vaccine effectivity was 90.6% (IC 95%: 27.9-98.8%) . CONCLUSIONS: Hib conjugate vaccine is effective in the Valencian Community, however, there is still invasive disease due to the low vaccine coverage and some vaccine failures.

Clin Biochem, 1998 Apr, 31(3), 143 - 50
Measurement of glutamine and glutamate by capillary electrophoresis and laser induced fluorescence detection in cerebrospinal fluid of meningitis sick children; Tucci S et al.; OBJECTIVES: Cerebrospinal fluid glutamine and glutamate concentrations were measured by CZE-LIFD in normal and meningitis sick children . DESIGN AND METHODS: A derivatization procedure for glutamine was optimized using CZE-LIFD . Cytochemical and bacteriological analysis were made to 152 CSF from children suspicious of suffering meningitis . RESULTS: CSF-glutamine concentration was lower in children with viral and bacterial meningitis . In addition, the group infected with Haemophilus influenzae had the lowest concentrations . By contrast, glutamate concentration was higher in children with meningitis . Glutamine concentration increased as the clinical condition of the patient improved . CONCLUSIONS: Lower concentrations of glutamine in children with bacterial meningitis might be due to the use of this amino acid for bacterial growth while higher concentrations of glutamate might be due to cell destruction . The results indicate that CZE-LIFD is an alternative tool for the determination of amino acids in CSF.

Arq Neuropsiquiatr, 1997 Jun, 55(2), 334 - 8
{Auditory behavior monitoring after bacterial meningitis . Case report}; Lichtig I et al.; Bacterial meningitis is the main cause for acquired hearing loss . Nevertheless very little has been written about the development of the auditory behaviour either for improvement or for deterioration, after hospital release . The present study describes the case of a five month old boy with Haemophilus influenzae meningitis . Amongst various complications, a decrement in the auditory acuity was detected in the immediate evolution, with significant improvement later on by qualitative and quantitative tests.

Biol Chem, 1998 Apr-May, 379(4-5), 575 - 8
Sequence similarities between the genes encoding the S.NgoI and HaeII restriction/modification systems; Stein DC et al.; The DNA sequence encoding the S.NgoI restriction/modification (R/M) system was identified from a gene bank made from Neisseria gonorrhoeae strain WR302 by identifying recombinant plasmids that induced the reporter system in a methylase detection strain AP1-200-9 (Piekarowicz et al., 1991) and were resistant to digestion with NgoI . The DNA sequence was determined from one of these (pUCP30) . M.NgoI is a protein of 315 aa with a predicted MW of 35296 Da and R.NgoI is a protein of 350 aa with a predicted MW of 40650 Da . The termination codon of M.NgoI overlapped the start codon of R.NgoI . The same strategy was used to clone the R/M system encoding HaeII from Haemophilus aegyptius strain ATCC 11116 . The DNA sequence from one clone representing this class (pAP704) was determined . HaeII methylase is a protein of 318 aa with a predicted MW of 35669 Da and R.HaeII contains 352 aa with a predicted MW of 40800 Da . aa alignments between the two methylases indicated that they were 74.3% identical and 79% similar . DNA sequence alignments revealed 68% identity . An aa alignment between the two restriction enzymes indicated that they were 60% identical and 68% similar . DNA sequence alignments revealed 61% identity . The DNA sequences flanking these two systems were identified and used to determine the genomic organization of the two systems . The S.NgoI genes were found between two genes, one with high homology to GTP binding proteins of unknown function and one with homology to genes involved in tRNA synthetase synthesis . The HaeII R/M genes were located between two genes, mucF and mucE . The DNA sequence of the HaeII R/M system was compared to the genomic DNA sequence of H . influenzae Rd . Although the DNA sequences flanking the HaeII system were > 99% identical to contiguous DNA fragments found in the genome of H . influenzae Rd, no homology was seen with the DNA sequences encoding the HaeII R/M system, indicating that it is not found in this strain . Given the vast difference in the GC content of S.NgoI and HaeII, their apparent insertion into polycistronic operons, and their difference in codon usage when compared to the species from which they were isolated, the data suggest that these R/M systems originated in an organism other than Neisseria or Haemophilus.

Acta Paediatr, 1998 Apr, 87(4), 375 - 7
Preoperative bacterial colonization of the upper airways does not predict postoperative airway infection in children; Gardlund B et al.; The aim of this prospective non-interventional investigation was to study whether preoperative colonization of nasopharynx with potentially pathogenic airway bacteria carried an increased risk for the development of early postoperative bacterial airway infections after heart surgery in preschool children . Of the 91 patients studied, 62 (68%) were colonized preoperatively in the nasopharynx with Moraxella catarrhalis, Streptococcus pneumoniae, Haemophilus influenzae and/or Staphylococcus aureus . Nine children developed postoperative airway infections (four pneumonia, three bacterial bronchitis and two acute otitis media) . Preoperative colonization was not significantly associated with increased risk for postoperative airway infection: 6/62 (10%) in colonized vs 3/29 (10%) in non-colonized children . Preoperative nasopharynx cultures in asymptomatic children should be avoided since it is unpleasant for the child, is not cost-effective, and may lead to unnecessary antibiotic treatment.

J Clin Immunol, 1998 May, 18(3), 193 - 201
Immunization with Haemophilus influenzae type b conjugate vaccine in children given bone marrow transplantation: comparison with healthy age-matched controls; Avanzini MA et al.; Forty-seven patients (age range, 7 months-18 years) with malignant (38 cases) and nonmalignant (9 cases) disorders given an allogeneic or an autologous bone marrow transplantation (BMT) were immunized with Haemophilus influenzae type b (Hib) polysaccharide-diphtheria toxoid conjugate vaccine administered in a single dose at different time points after transplantation . Results were compared with those of 13 healthy children matched for age and sex who received the same immunization schedule . Serum and saliva samples for measurement of total IgG subclass and specific antibody levels were obtained from patients and healthy controls before and 3 weeks after vaccination . Twenty-five of the 47 patients (53%) had a specific anti-Hib IgG response, while an effective IgA and IgM response was mounted by 23 (49%) and 11 (23%) children, respectively . In the control group, 13 of 13 subjects mounted a specific IgG antibody production (P < 0.005 in comparison to the patients' response rate), while an IgA and IgM response was demonstrated in 12 (92%; P < 0.01 compared to transplanted patients) and 7 (54%; P < 0.05 in comparison to BMT recipients) children, respectively . Lapse of time from BMT to immunization was the most important factor predicting antibody response, as proved by an effective increase in prevaccination specific IgG levels in the majority of patients vaccinated after 2 years from transplant . Our data demonstrate that BMT recipients have a reduced capacity to mount an antibody response to polysaccharide antigens compared to normal controls, even when a protein-conjugated vaccine is employed . Since time after transplant is the major factor influencing the recovery of immune reactivity to polysaccharide antigens, the ontogeny of the B cell repertoire seems to follow a predetermined sequential program of development.

J Laryngol Otol, 1998 Mar, 112(3), 264 - 8
Antibiotic choice in acute and complicated sinusitis; Mortimore S et al.; The microbiology of 87 patients admitted to hospital, over a five-year period, with acute sinusitis was retrospectively analysed . Sixty-three patients had one or more of an orbital, intracranial, soft tissue or bony complication . Eighty-four patients had maxillary sinus washouts, while 48 required a surgical procedure to their sinuses, and 33, drainage of an empyema . Streptococcus milleri and Haemophilus influenzae were the commonest organisms isolated from sinus aspirates (44 per cent), with a noticeable absence of Streptococcus pneumoniae (10 per cent) . Organisms cultured from intracranial, soft tissue or orbitral empyemas were predominantly Streptococcus milleri (50 per cent) and Staphylococcus aureus (25 per cent) with an absence of Haemophilus influenzae (four per cent) and Streptococcus pneumoniae (four per cent) . Ampicillin is an appropriate first line antimicrobial agent in patients with acute complicated sinusitis with the addition of cloxacillin in cases with an empyema . Chloramphenicol or ceftriaxone is used in cases with an intracranial complication.

Clin Infect Dis, 1998 Apr, 26(4), 964 - 71
Pyogenic bacterial pneumonia in human immunodeficiency virus-infected inpatients: a clinical, radiological, microbiological, and epidemiological study; Baril L et al.; We prospectively studied features of pyogenic bacterial pneumonia in 263 consecutive human immunodeficiency virus-infected inpatients over a 6-month study period . Risk factors for bacterial pneumonia were examined by a case-control study that included 33 cases who presented with at least one episode of bacterial pneumonia and 80 controls without bacterial pneumonia . The estimated cumulative incidence of bacterial pneumonia per year was 12.5 cases per 100 inpatients (95% confidence interval {CI}, 8.8-17.2) . The 38 episodes of bacterial pneumonia that occurred in the 33 inpatients were mainly unilateral, but 32 episodes were patchy lobar or diffuse infiltrates . Microbiological etiologies were obtained in 33 of the 38 episodes of bacterial pneumonia . Thirty-seven pathogens were identified, including Streptococcus pneumoniae (16, of which 12 had a decreased susceptibility to penicillin), Haemophilus influenzae (6), and Pseudomonas aeruginosa (6) . The risk factors for bacterial pneumonia that were identified after logistic regression included prior sinusitis within 1 month before admission (odds ratio {OR}, 3.2; 95% CI, 1.1-9.1) and prior bacterial infection of the lower respiratory tract within 6 months before admission (OR, 3.1; 95% CI, 1.1-8.3).

Ned Tijdschr Geneeskd, 1998 Mar 14, 142(11), 586 - 9
{Invasive infection with Haemophilus influenzae type b in spite of complete vaccination}; Breukels MA et al.; Five patients, 4 boys and 1 girl aged 13-41 months, developed invasive Haemophilus influenzae type b (Hib) disease (2 epiglottitis, 3 meningitis) despite full (or at least 3 times) vaccination . At admission as well during convalescence, 3 out of 5 had IgG anti Hib antibody levels < or = 5 U/ml . Serum immunoglobulin levels, including IgG subclasses, as well as complement were normal in all cases . In 2 of the 3, booster vaccinations with Hib conjugate vaccine elicited adequate antibody titres . Since the incorporation of the conjugated Hib polysaccharide tetanus toxoid vaccine (HibTT) in the National Vaccination Programme in the Netherlands, the number of invasive infections caused by Hib has dropped significantly . Causes of Hib conjugate vaccine failures are mostly unknown . In about one-third of the cases serum immunoglobulin levels are deficient, most often IgG2 or IgM . Susceptibility to Hib infection is in part also genetically determined . In the follow-up of Hib vaccine failures, anti Hib antibody titres should be determined . Booster vaccinations may be necessary.

Emerg Infect Dis, 1998 Apr-Jun, 4(2), 229 - 37
Haemophilus influenzae invasive disease in the United States, 1994-1995: near disappearance of a vaccine-preventable childhood disease; Bisgard KM et al.; We analyzed national Haemophilus influenzae (Hi) surveillance data from 1994 and 1995 to describe the epidemiology of Hi invasive disease among persons of all ages . Serotype data were available for 376 (56%) of 669 reported Hi cases among children aged 4 years or younger; 184 (49%) were H . influenzae type b (Hib) . Among children aged 4 or younger, incidence (per 100,000) of all Hi invasive disease was 1.8 in 1994 and 1.6 (p < 0.05) in 1995 . Children aged 5 months or younger had the highest average annual incidence rate of Hib invasive disease (2.2 per 100,000); children aged 6 to 11 months had the next highest rate (1.2 per 100,000)(p < 0.05) . Of 181 children with Hib invasive disease whose age in months was known, 85 (47%) were too young (aged 5 months or younger) to have completed a primary series with an Hib-containing vaccine . Of the 83 children with known vaccination status who were eligible to receive a primary series (aged 6 months or older), 52 (63%) were undervaccinated, and the remaining 31 (37%) had completed a primary series in which vaccine failed . Among persons aged 5 years or older with Hi invasive disease, the lowest average annual incidence was among those 20 to 39 years of age (0.15 per 100,000), and the highest was among those aged 80 years or older (2.26 per 100,000) . Among persons aged 5 years or older, serotype data were available for 1,372 (71%) of the 1,940 Hi invasive disease cases; 159 (28%) of the 568 Hi cases with known serotype were due to Hib.

J Bone Joint Surg Br, 1998 May, 80(3), 471 - 3
Reduced incidence of septic arthritis in children by Haemophilus influenzae type-b vaccination . Implications for treatment; Peltola H et al.; In many countries Haemophilus influenzae type b (Hib) is the second most common cause of septic arthritis in children . In Finland large-scale immunisation against Hib using conjugate vaccines began in 1986, four years after a multicentre prospective study of orthopaedic infections in children had started . Since 1982, including six years before and ten after starting routine Hib vaccination, there has been a major change in the pattern of septic arthritis . From 1982 to 1988, 32 of 61 cases (53%) were caused by staphylococci, 22 (36%) by Hib and 7 (11%) by other bacteria . Since 1988, Hib infection has disappeared, and one-third of cases of childhood septic arthritis has been eliminated . This change has allowed us to reduce initial antimicrobial therapy for such children to cover only Gram-positive cocci . The more limited treatment is safer, reduces cost, and simplifies treatment.

Microbiol Mol Biol Rev, 1998 Jun, 62(2), 294 - 308
Nontypeable Haemophilus influenzae: pathogenesis and prevention; Foxwell AR et al.; In this paper, we describe the ability of nontypeable Haemophilus influenzae (NTHi) to coexist with the human host and the devastating results associated with disruption of the delicate state of balanced pathogenesis, resulting in both acute and chronic respiratory tract infections . It has been seen that the strains of NTHi causing disease show a marked genetic and phenotypic diversity but that changes in the lipooligosaccharide (LOS) and protein size and antigenicity in chronically infected individuals indicate that individual strains of NTHi can remain and adapt themselves to avoid expulsion from their infective niche . The lack of reliance of NTHi on a single mechanism of attachment and its ability to interact with the host with rapid responses to its environment confirmed the success of this organism as both a colonizer and a pathogen . In vitro experiments on cell and organ cultures, combined with otitis media and pulmonary models in chinchillas, rats, and mice, have allowed investigations into individual interactions between NTHi and the mammalian host . The host-organism interaction appears to be a two-way process, with NTHi using cell surface structures to directly interact with the mammalian host and using secreted proteins and LOS to change the mammalian host in order to pave the way for colonization and invasion . Many experiments have also noted that immune system evasion through antigenic variation, secretion of enzymes and epithelial cell invasion allowed NTHi to survive for longer periods despite a specific immune response being mounted to infection . Several outer membrane proteins and LOS derivatives are discussed in relation to their efficacy in preventing pulmonary infections and otitis media in animals . General host responses with respect to age, genetic makeup, and vaccine delivery routes are considered, and a mucosal vaccine strategy is suggested.

Respir Med, 1998 Feb, 92(2), 233 - 40
Epithelial cell damage is induced by neutrophil-derived, not pseudomonas-derived, proteases in cystic fibrosis sputum; Venaille TJ et al.; Airway histopathological changes in cystic fibrosis (CF) include damage to the epithelial tissue and accumulation of polymorphonuclear leukocytes (PMN) . Airways of CF patients are usually colonized with bacteria such as mucoid Pseudomonas aeruginosa (PA) . Bacteria and PMN can both release proteolytic enzymes capable of causing tissue damage . This study aims to clarify and compare the roles of these agents in epithelium damage . Epithelial cell (EC) damage and detachment induced by sputum samples from CF or non-CF patients, with and without lung infection, were assessed on amnionic EC in an in vitro model of airway epithelium . Protease activity was determined using inhibitor profiles, and compared to the proteolytic activity of isolated neutrophils and bacteria . Sputa from CF patients and infected non-CF patients induced high levels of detachment . PA also induced high levels of EC detachment but Staphylococcus aureus and Haemophilus influenzae, two other bacteria commonly isolated from CF sputa, induced no detachment . Antiprotease inhibition profiles were similar for PMN and sputa-induced EC detachment, but different for PA-induced detachment . These results suggest that PMN proteolytic enzymes, probably elastase and cathepsin G, are more likely to be the inducers of tissue damage in the airways of CF patients than PA proteolytic enzymes.

Vet Immunol Immunopathol, 1998 Feb 27, 61(2-4), 279 - 89
Inducible nitric oxide synthase expression in porcine immune cells; Pampusch MS et al.; Porcine immune cells were examined for the ability to produce inducible nitric oxide synthase following in vitro or in vivo stimulation . Enzyme activity and product formation were not detected following stimulation of porcine peripheral blood mononuclear cells (PBMC), splenocytes, or alveolar macrophages with a combination of ConA and lipopolysaccharide (LPS) or recombinant porcine interferon gamma and LPS . In vitro engulfment of Haemophilus parasuis by macrophages also failed to induce inducible nitric oxide synthase (iNOS) activity or nitrite formation . Swine Herpes Virus infection led to a small but significant increase in level of nitrite detected in lung lavage fluid, whereas the infection of pigs with Porcine Respiratory and Reproductive Syndrome Virus did not alter the lavage fluid nitrite levels . iNOS mRNA was detected in both stimulated and unstimulated porcine immune cells and in macrophages from both control and infected animals suggesting that it is constitutively expressed with little or no upregulation following cellular stimulation . The results presented in this paper indicate that the reactive nitrogen intermediate pathway is not an vital innate immune response in the pig.

Scand J Prim Health Care, 1998 Mar, 16(1), 13 - 7
The prevalence of potential pathogenic bacteria in nasopharyngeal samples from healthy children and adults; Gunnarsson RK et al.; OBJECTIVE: To elucidate the prevalence of potential pathogenic bacteria in nasopharyngeal samples from healthy individuals, and the influence on the carrier rate of age, season of the year, and type of child day care . DESIGN: Nasopharyngeal swab samples obtained in routine medical care from individuals with no sign of infection were studied in 159 pre-school children aged below 7 years, 198 schoolchildren aged 7-15 years, and 261 adults (.16 years) . RESULTS: The prevalence of pathogenic bacteria in healthy individuals decreased with age . The overall isolation frequencies for pre-schoolchildren, schoolchildren, and adults, respectively, were: Moraxella catarrhalis (27%, 4% and 2%); Streptococcus pneumoniae (19%, 6% and 0.8%); Haemophilus influenzae (13%, 6% and 3%) . The prevalence of S . pneumoniae in children 7-15 years was higher during the summer than in the winter . We could not confirm any variation in the carrier rate due to the type of child day care . CONCLUSION: Potentially pathogenic bacteria are often present in nasopharyngeal samples taken from healthy pre-school children, but rarely from people > or = 16 years of age . This means that the use of nasopharyngeal samples to discriminate between bacterial and viral respiratory tract infection needs to be evaluated further in patients < 16 years . The importance of the seasonal variation in the prevalence of potential pathogenic bacteria in the nasopharynx needs further study.

Med Pregl, 1998 Mar-Apr, 51(3-4), 151 - 4
{Primary infection with varicella-zoster virus in risk groups}; Jovanovic J et al.; INTRODUCTION: Chickenpox represents the primary form of Varicella-zoster virus (VZV) infection and appears most commonly in preschool and school children . The clinical course of chickenpox in immunocompetent children is mainly mild and complications are rare (1-5) . Adults and immunocompromised patients are considered to be risk groups for development of serious and even life-threatening complications . The most frequent bacterial complications include secondary bacterial skin infections, angina, sinusitis, otitis and bronchopneumonia . Central nervous system complications, visceral dissemination, pneumonitis and myocarditis are the major viral complications (6,7) . Acyclovir is approved for treatment of chickenpox in risk groups to reduce the frequency of viral complications and to treat those ones which have already appeared (7,8) . The treatment of bacterial complications is based on the examination results of the bacterial sensitivity to antibiotics . MATERIAL AND METHODS: In our study patients with the diagnosis of chickenpox based on the history of disease, clinical features and clinical course and data on intimate contact with individuals suffering from chickenpox, were clinically followed-up . Sedimentation rate, blood count and urine samples were analyzed . A unique questionnaire was designed to follow-up the following data: sex, age, course of the disease, occurrence of complications in immunocompetent patients and those belonging to risk groups and effects of acyclovir therapy . RESULTS: During a three-year period 48 patients with chickenpox treated at the Clinic of Infectious and Dermatovenereology Diseases have been observed . 64.6% of them were males and 35.4% were females . 29.2% were infants under 1 year of age, 29.2% were 2-13 years of age and 41.6% were 14-50 years of age . According to the clinical course, patients were divided into two groups: the first one included patients who developed complications of chickenpox (54.1%), the second one consisted of those without complications (45.1%) . 72.7% of all complications occurred in patients belonging to risk group (14-50 years of age) . Among viral complications in risk groups the most common were pneumonia (44.4%) and haemorrhagic rash (44.4%), only one patient (11.1%) developed a mild, viral meningitis . Bacterial complications were also present in risk group as secondary bacterial skin infections (71.4%) and otitis media (28.6%) . Viral complications were treated successfully by 750 mg intravenous acyclovir given 3 times a day, or by 800 mg oral acyclovir given 5 times a day during 7-10 days . Adequate antibiotics were used in the treatment of bacterial complications . A case of chickenpox associated with the meningitis caused by Haemophilus influenzae was also reviewed . DISCUSSION: In this study the majority of observed patients had a mild, clinical form of chickenpox that is in accordance with the other available clinical data (1-4) . Complications developed more frequently in the adults and usually were of viral etiology . All patients were on time treated with acyclovir and visceral dissemination did not occur in any of them . Complications had a favourable evolution and VZV meningitis was healed without sequelae . Many authors have written about successful use of acyclovir in the treatment of chickenpox . However, acyclovir is not recommended to immunocompetent persons without chickenpox viral complications who do not belong to risk groups (1,3,4,9-11) . CONCLUSION: Our findings lead to the conclusion that chickenpox in adults may have an uncertain outcome because of a more severe clinical course and susceptibility to complications . In our study application of acyclovir in that age group provided good results as for prevention and treatment of complications of chickenpox if already manifested.

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