Haemophilus

J Clin Microbiol, 1995 Jun, 33(6), 1486 - 91
Rapid bacterial antigen detection is not clinically useful; Perkins MD et al.; Latex agglutination (LA) of capsular polysaccharide bacterial antigen is a frequently performed laboratory procedure, but its use is controversial . To assess the clinical utility of this test, we reviewed all LA tests performed over a 10-month period at two sites, a major university-based referral center and a private specialty pediatric hospital . Samples were assayed either individually or as a panel for the group B streptococcus, Streptococcus pneumoniae, Haemophilus influenzae, and three sets of Neisseria meningitidis serogroups (A and Y, C and W135, and B and Escherichia coli K1) . Of 5,169 assays performed on 1,268 clinical samples (786 urine and 478 cerebrospinal fluid, 3 pleural fluid, and 1 synovial fluid sample), 57 (1.1%) were positive, including 1.7% of urine and 0.3% of cerebrospinal fluid samples . All LA true-positive cerebrospinal fluid samples showed the causative microorganisms by Gram stain . Detailed chart review of these 57 positive samples showed that the LA result was false-positive in 31 (54%), true-positive in 22 (38%), and indeterminate in 4 (7%) samples . Therapy was not altered on the basis of any of the true-positive LA results . The 31 false-positive results led to additional cost, prolonged hospitalization, and some clinical complications . Total patient charges were $175,000 ($7,954 per true-positive), with no detectable clinical benefit . Our retrospective study does not support the current use of LA for rapid antigen detection . What, if any, specific indications exist for this test remain to be elucidated.

J Fla Med Assoc, 1995 Jun, 82(6), 401 - 2
Cost-effectiveness of Haemophilus influenzae type b conjugate vaccine program in Florida; Midani S et al.; Introduction of Haemophilus influenzae type b (Hib) vaccine has significantly decreased this disease's incidence in childhood . The cost-effectiveness and economic impact of the Hib immunization program in Florida were investigated and three periods compared: I = 1984-1988; II = 1989-1990; and III = 1991-1992 . The cost per year of Hib disease in Period I was $27.48 million while that in Periods II and III was $15.95 million and $.88 million respectively . The total savings in millions were: Periods I and II = $11.53; Periods II and III = $11.07; and Periods I and III = $22.6 . The greatest saving was realized between Periods I and III because of the initiation of immunization with the Hib vaccine starting at two months of age during Period III . Hib immunization is cost-effective and significant savings would more than pay for the cost of the program.

Drugs, 1995 Jun, 49(6), 1007 - 22
Cefixime . A review of its therapeutic efficacy in lower respiratory tract infections; Markham A et al.; Cefixime is an orally active third generation cephalosporin with in vitro antibacterial activity against most important lower respiratory pathogens . The drug is active against Haemophilus influenzae, Moraxella catarrhalis and penicillin-susceptible Streptococcus pneumoniae but not Staphylococcus aureus . Cefixime has a long elimination half-life (3 hours compared with 0.5 hours for cefaclor and 1.5 hours for cefalexin), which allows once daily administration . Several trials have established the clinical efficacy of the drug in patients with lower respiratory tract infection (LRTI) . In comparative studies cefixime had similar efficacy to amoxicillin +/- clavulanic acid, cefaclor, cefalexin, cefuroxime axetil and clarithromycin . Trials evaluating the efficacy of cefixime as the oral component of intravenous to oral switch therapy have produced promising preliminary results although further carefully designed trials are needed in this area . As with certain other drugs of its class, gastrointestinal disturbances are the most frequently reported adverse events in patients taking cefixime and cases of pseudomembranous colitis have been reported . Thus, cefixime is an effective treatment for mild to moderate LRTI and may have a role as the oral component of intravenous to oral switch therapy although further well designed studies are needed to confirm initial favourable results in this important emerging area of antibacterial therapy.

Immunol Cell Biol, 1995 Jun, 73(3), 258 - 65
Protection against non-typable Haemophilus influenzae following sensitization of gut associated lymphoid tissue: role of specific antibody and phagocytes; Wallace FJ et al.; Rats intestinally immunized with whole killed non-typable Haemophilus influenzae clear this organism from the lungs faster than non-immunized rats . This study investigated the role of antibody and phagocytes in the clearance mechanism . First, dose-response experiments demonstrated that while lowering the dose of non-typable H . influenzae reduced the level of detectable specific antibody in bronchial washings, the ability to accelerate bacterial clearance persisted to much lower doses . Second, specificity experiments showed that intestinal immunization with non-typable H . influenzae cross-protected against Pseudomonas aeruginosa, even though antibodies were not absorbed out of serum by incubation with P . aeruginosa . Third, serum antibody was shown to be bactericidal for non-typable H . influenzae in the presence of complement (P < 0.05), while bronchial washings antibody was not . The bactericidal effect of the serum was abrogated by the addition of bronchial washings . Fourth, an ELISA quenching assay demonstrated that neutrophils from intestinally immunized rats were able to phagocytose more bacteria in a given time period (P < 0.05) than unimmunized rats and rats immunized by other routes . In the fifth experiment, the chemotactic response of neutrophils to casein was shown to be significantly depressed by the addition of bronchial washings obtained from immunized rats (P < 0.01) . It is proposed that specific antibody in bronchial washings does not have a direct role in opsonizing bacteria for killing or phagocytosis, but instead has an anti-inflammatory effect . Non-specific effectors such as neutrophils driven by specific immune cells are a likely means of clearance of bacteria following intestinal immunization and acute challenge.

Fam Pract, 1995 Jun, 12(2), 155 - 8
The high vaginal swab in general practice: clinical correlates of possible pathogens; Dykhuizen RS et al.; Clinical features, diagnosis and treatment of 286 women whose high vaginal swabs (HVS) submitted by their general practitioners showed pure, heavy growth of Staphylococcus aureus, beta haemolytic streptococci groups A, C or G, Streptococcus milleri, Streptococcus pneumoniae or Haemophilus influenzae were analysed . Women with group A, C and G streptococci frequently had clinical vulvovaginitis and although the numbers were too small for statistical confirmation, S . pneumoniae and H . influenzae appeared to cause clinical disease as well . The association of S . aureus or S . milleri with clinical vulvovaginitis was much less convincing . It seems relevant for laboratories to report sensitivities for group A, C and G streptococci . Further research is needed to determine the pathogenicity of S . pneumoniae and H . influenzae.

Eur Respir J, 1995 Jun, 8(6), 948 - 53
The isolation and characterization of non-typeable Haemophilus influenzae from the sputum of adult cystic fibrosis patients; Bilton D et al.; The role of non-typeable Haemophilus influenzae in cystic fibrosis (CF) remains unclear . We wanted, therefore, to determine the presence and characteristics of non-typeable H . influenzae in sputum samples from patients with CF . In order to do this, we have assessed sputum samples from 55 consecutive clinically stable patients seen routinely at an adult CF out-patient clinic . Quantitative bacterial culture was performed using a selective media containing cefsoludin, and isolates were characterized by biotyping and outer membrane protein profile analysis . In 17 (30%) of these samples, non-typeable H . influenzae was isolated and was present in similar viable numbers (mean 7.7 x 10(8) colony-forming units (cfu).mL-1; SEM 3.1) to Pseudomonas aeruginosa (mean 8 x 10(8) cfu.mL-1: SEM 2.4) . All non-typeable H . influenzae isolates recovered were beta-lactamase negative and sensitive to a range of antibiotics . Several biotypes and outer membrane protein profiles were observed, with no apparent association between these two phenotypic characteristics . The study showed that large numbers of non-typeable H . influenzae are often present in sputum from adult patients with CF . Further longitudinal studies of outer-membrane protein profile analysis are required to determine the dynamics of non-typeable H . influenzae colonization in individual patients and the clinical significance.

Allergy, 1995 Jun, 50(6), 528 - 31
Characterization of the antibody response to a Haemophilus influenzae type b conjugate vaccine in children with recurrent lower respiratory tract infection; Kristensen K et al.; Children with recurrent lower respiratory tract infection (RLRI) may respond poorly to polysaccharide antigens . To examine how such children respond to a polysaccharide coupled to a protein carrier, we immunized 15 children with RLRI aged 8-69 months and 15 carefully age-matched healthy controls once with a Haemophilus influenzae type b (Hib) conjugate vaccine . Total IgG subclasses, total antipolysaccharide Hib antibodies, and antipolysaccharide Hib antibodies of IgM, IgG, IgA, and IgG1-4 specificity were determined by ELISA . There were no significant differences between the two groups in any single total IgG subclass, but total IgG measured as the sum of all four subclasses was significantly lower in the children with RLRI than in the controls (P = 0.036) . Before vaccination, the children with RLRI had significantly less IgG antipolysaccharide Hib antibody than the controls (P = 0.005), whereas 1 month later they had significantly more IgM antibody (P = 0.038) . No other significant differences were found between the groups before or after immunization with respect to antipolysaccharide Hib antibodies . Since naturally occurring IgG antibodies are thought to be acquired partly as a consequence of antigenic stimulation on mucosal surfaces, we hypothesize that the low level of specific IgG found before immunization, as well as the low total IgG in the children with RLRI, may reflect an impaired ability to prime through mucosal surfaces . This is supported by our finding of an increased IgM response to Hib conjugate vaccine in these children, since this isotype predominates in the primary immune response, i.e., in the absence of immunologic memory.(ABSTRACT TRUNCATED AT 250 WORDS)

Oral Microbiol Immunol, 1995 Jun, 10(3), 151 - 9
Molecular and immunological characterization of a 64-kDa protein of Actinobacillus actinomycetemcomitans; Nakano Y et al.; The 64-kDa protein to which about half the sera from patients with localized juvenile periodontitis and rapidly progressive periodontitis reacted strongly was purified from Actinobacillus actinomycetemcomitans Y4 . Determination of the N-terminal sequence of the protein revealed that it was a GroEL-like protein . The DNA fragment containing the groEL gene of A . actinomycetemcomitans was amplified by polymerase chain reaction, and the groESL operon was cloned by using colony hybridization with the amplified fragment from A . actinomycetemcomitans chromosomal DNA . Sequence analysis revealed that structures of the operon and its products were typical in gram-negative bacteria . Rabbit polyclonal antibodies to the 64-kDa protein cross-reacted with approximately 65-kDa proteins of Haemophilus aphrophilus, Haemophilus influenzae, Haemophilus paraphrophilus, Escherichia coli and Eikenella corrodens but not with any cellular proteins of Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum . It is possible that antibodies reactive to the 64-kDa protein in periodontitis patients are induced by the cross-reactivity with the hsp60 proteins of other bacteria.

J Hosp Infect, 1995 Jun, 30 Suppl, 313 - 21
Use of conjugate vaccines to prevent meningitis caused by Haemophilus influenzae type b or Streptococcus pneumoniae; Eskola J; Antibodies to the capsular polysaccharides of Haemophilus influenzae type b or Streptococcus pneumoniae protect against meningitis caused by these bacteria . Many of the polysaccharides are poorly immunogenic, especially in infants, but can be turned to highly immunogenic vaccines by covalent conjugation to a protein carrier . On the basis of the good protection observed in several trials, H . influenzae type b conjugates have been accepted for wide use . This experience has also provided direction for the development of new conjugates against infections caused by the most common serotypes of S . pneumoniae . First results from immunogenicity studies of these pneumococcal conjugate vaccines are promising.

Clin Otolaryngol, 1995 Jun, 20(3), 219 - 23
The microbiology and antibiotic treatment of peritonsillar abscesses; Prior A et al.; Pus from 53 peritonsillar abscesses was cultured and associations between the microbiological results and clinical data were investigated with the aim of developing a clinical protocol for treatment . A positive culture grew in 85% of quinsies and of these 16% produced aerobes and 84% anaerobes . Penicillin-resistant organisms were grown from 32% of patients and all but one of these organisms (Haemophilus influenzae) was sensitive to metronidazole . There was no association between clinical presentation and cultured organism which could guide treatment, hence we recommend penicillin and metronidazole as the antibiotic regimen of choice in the treatment of peritonsillar abscesses because of its effectiveness in 98% of patients.

J Formos Med Assoc, 1995 Jun, 94(6), 351 - 4
Serotypes, biotypes and antibiotic susceptibility of 126 clinical isolates of Haemophilus influenzae; Chiu CH et al.; Serotypes, biotypes, and antibiotic susceptibility of 126 Haemophilus influenzae isolates were determined . Five of the 126 isolates were from blood and were encapsulated type b strains; those taken from other sites were not typable . There were 13% biotype I, 36% biotype II, 38% biotype III, 5% biotype IV, 4% biotype V, and 4% biotype VI isolates . Antibiotic susceptibility tests using the standard disk diffusion method showed the following resistance: ampicillin 51%, cefamandole 10%, cefuroxime 3%, chloramphenicol 28%, tetracycline 37% and sulfamethoxazole-trimethoprim 49% . None of the five type b isolates were resistant to cefotaxime, a third generation cephalosporin . The second generation cephalosporins, cefamandole and cefuroxime, showed a superior activity against H . influenzae isolates, compared to other antibiotics . Multiple drug resistance was found in 64 (51%) isolates . Four of the five type b isolates were resistant to multiple drugs . The multiple-resistance pattern most frequently observed was to ampicillin, chloramphenicol, tetracycline and sulfamethoxazole-trimethoprim . Most clinical isolates did not contain plasmids; therefore, the antibiotic resistance of these H . influenzae strains was probably chromosome-mediated.

East Afr Med J, 1995 Jun, 72(6), 376 - 8
Analysis of the results of routine lumbar puncture after a first febrile convulsion in Hofuf, Al-Hassa, Saudi Arabia; Laditan AA; Cerebrospinal fluid (CSF) was analysed to determine a lumbar puncture (LP) yield for meningitis in 95 children who presented with their first febrile convulsions between July 1993 and June 1994 . There were 52 males and 43 females aged six months to six years with a mean age of 21.9 +/- 13.0 months at presentation . 87(91.6%) had simple febrile convulsions (SFC) while the remaining 8(8.4%) had complex febrile convulsions (CFC) . The majority of the subjects presented with a sudden onset of convulsions that were preceded by a day or two history of fever, coryza, cough and respiratory distress while others had their convulsions preceded by fever and passage of bloody stools . The LP yield for meningitis in this series was 6.3% . The CSF analysis revealed six cases of meningitis comprising an eight month old infant with Haemophilus influenzae type B (HIB) meningitis, two partially treated pyogenic meningitis and three aseptic meningitis . All of them had presented with febrile convulsions without signs of meningeal irritation . Excluding aseptic meningitis from this series, a 3.1% LP yield for pyogenic meningitis is significant enough to recommend continued performance of LP in children with first febrile convulsions, especially if under the age of eighteen months.

Ann N Y Acad Sci, 1995 May 31, 754, 289 - 99
Defining surrogate serologic tests with respect to predicting protective vaccine efficacy: poliovirus vaccination; Sutter RW et al.; Inactivated and trivalent oral poliovirus vaccines contain either formalin-inactivated or live, attenuated poliovirus, respectively, of the three serotypes . Interference among the three attenuated poliovirus serotypes was minimized with a "balanced-formulation" vaccine, and serologic responses after IPV were optimized by adjusting the antigenic content of each inactivated poliovirus serotype . Seroconversion is dependent on both the relative content as well as the absolute quantity of virus in the vaccine . The "gold standard" method to assess humoral antibody responses following vaccination is the neutralization assay . Any detectable titer of neutralizing antibody against poliovirus is considered protective against clinical paralytic diseases . Recently, standard procedures were adopted for conducting neutralization assays . Efforts are being undertaken now to develop a combined diphtheria and tetanus toxoids and pertussis vaccine and IPV vaccine in the United States using a dual-chambered syringe that mixes the content of both vaccines at the time of injection; this approach is necessary to overcome the potential detrimental effect of thimerosal on IPV (the preservative in DTP) . Other vaccines that combine DTP and/or Haemophilus influenzae type b and/or hepatitis B with IPV appear feasible but require further investigation . New combination vaccines should induce similar or superior levels of neutralizing antibody in serum for individual protection against paralytic disease and mucosal immunity that effectively decreases viral replication in the intestine and pharynx for population protection against transmission of poliovirus.

Ann N Y Acad Sci, 1995 May 31, 754, 278 - 88
Laboratory correlates of protection against Haemophilus influenzae type b disease . Importance of assessment of antibody avidity and immunologic memory; Granoff DM et al.; The concentration of serum antibody to the Haemophilus influenzae type b polysaccharide sufficient to confer protection against Hib disease has been estimated to range from 0.15 to 1.0 microgram/ml as measured by conventional antigen binding assays . However, the ability of these serologic tests to predict vaccine equivalence and/or protective efficacy is limited since there are important qualitative differences in vaccine-induced anti-PRP antibody, such as isotype, variable region usage, and antibody avidity . These differences may profoundly affect the biologic activity of the antibody . Also, Hib conjugate vaccination primes infants for memory antibody responses to a subsequent encounter with PRP, and immunologic priming can occur in infants with very low serum anti-PRP antibody responses to conjugate vaccination, or in those whose antibody concentrations have declined after vaccination . Primed infants are likely to be protected against Hib disease in the absence of "protective" serum antibody concentrations because priming permits a rapid serum anti-PRP antibody response upon encountering the organism . Thus, quantitative assessment of immunogenicity, by itself, is insufficient to predict vaccine equivalence or protective efficacy . In defining surrogate serologic tests for prediction of vaccine efficacy, assessments of antibody avidity and induction of immunologic memory should be included . Ideally, these assessments should be supplemented with antibody functional assays such as complement-mediated bactericidal activity, opsonic activity, or passive protection in animal models of disease.

Ann N Y Acad Sci, 1995 May 31, 754, 108 - 13
Combination vaccines for diphtheria, tetanus, pertussis, and Haemophilus influenzae type b; Paradiso PR; The ability to combine the standard DTP and Haemophilus b conjugate vaccine considerably simplifies the childhood immunization schedule and process . In addition to reducing the number of immunizations by half, the combination product reduces administrative aspects associated with vaccination including tracking . Simplification of the immunization process should have a positive impact on the vaccine delivery and utilization . Perhaps more importantly, an ability to create combination vaccines will be critical for inclusion of new antigens appropriate for infant vaccines . The combination of DTP and HbOC reduces the number of immunizations routinely given at 2, 4, and 6 months of age by half . Since it is unlikely that parents or pediatricians will accept more than two shots per visit, this reduction is critical . As new vaccines are licensed for such important childhood pathogens as Streptococcus pneumoniae and respiratory syncytial virus, designing stable combination products will become even more critical . Having stated that, we must also not lose site of the fact that combination products must meet the criteria for stability, safety, and efficacy comparable to the separately delivered products . These considerations are not trivial . In the development of Tetramune (DTP-HbOC), stability of the product and consistency of the immune response were critical design parameters for both the preclinical and clinical research . Likewise, the experience with other DTP-Haemophilus b combinations has shown that simple mixing of products prior to injection can reduce the immune response in ways that are not necessarily predictable . In contrast, the response to each of the components of Tetramune was in fact higher than when the vaccines were given separately . This increased response to all of the antigens was not anticipated based on the vaccine composition and points to the need for not only physical characterization of new combinations, but also clinical testing of final combined products before they are introduced for routine use.

JAMA, 1995 May 24-31, 273(20), 1598 - 604
Molecular analysis of bacterial pathogens in otitis media with effusion; Post JC et al.; OBJECTIVE--To determine if the polymerase chain reaction (PCR) can detect bacterial DNA in pediatric middle ear effusions that are sterile by standard cultural methods . DESIGN--Single-center, blinded, comparative study of diagnostic assays . The PCR-based detection systems for Moraxella catarrhalis, Haemophilus influenzae, and Streptococcus pneumoniae were designed and validated using a battery of DNAs obtained from cultured bacteria . Chronic middle ear effusion specimens were collected and comparatively analyzed by culture and the PCR . SETTING--Tertiary care pediatric hospital . PATIENTS--A total of 97 middle ear effusions were collected from pediatric outpatients at Children's Hospital of Pittsburgh (Pa) during myringotomy and tube placement for chronic otitis media with effusion (duration > 3 months) . All patients had failed multiple courses of antimicrobial therapy and were diagnosed by a combination of validated otoscopy and tympanograms . MAIN OUTCOME MEASURE--Differences in the percentage of positive test results between PCR-based assays and culture for M catarrhalis, H influenzae, and S pneumoniae . RESULTS--Of the 97 specimens of otitis media with effusion, 28 (28.9%) tested positive by both culture and PCR for M catarrhalis, H influenzae, or S pneumoniae . An additional 47 specimens (48%) were PCR positive/culture negative for these three bacterial species . Thus, 75 (77.3%) of the 97 specimens tested PCR positive for one or more of the three test organisms . The minimum number of bacterial genomic equivalents present in the average culture-negative ear was estimated to be greater than 10(4) based on dilutional experiments . CONCLUSIONS--The PCR-based assay systems can detect the presence of bacterial DNA in a significant percentage of culturally sterile middle ear effusions . While this finding is not proof of an active bacterial infectious process, the large number of bacterial genomic equivalents present in the ears is suggestive of an active process.

Tidsskr Nor Laegeforen, 1995 May 20, 115(13), 1604 - 6
{Vaccine against Haemophilus influenzae type b--antibody response and adverse effects}; Nokleby H et al.; In 1992 it was decided to implement vaccination against Haemophilus influenzae type b (Hib) in the Norwegian vaccination programme . The chosen vaccine consists of Hib-polysaccharide conjugated to tetanus toxoid . To suit the Norwegian vaccination schedule, Hib-vaccine was given together with vaccine against diphtheria, tetanus and pertussis (DTP) at three, five and ten months of age . Since all earlier studies with the Hib-vaccine have used other time schedules, a pilot study was conducted to test antibody response and side effects when using the Norwegian schedule . 44 infants were vaccinated with Hib-vaccine and DTP at three, five and ten months of age . Blood samples showed that 95% had protective antibody titer against Hib after two doses, 100% after three . The response to the other antigens was adequate . There were only minor side effects . After introduction of the Hib-vaccine the incidence of invasive Hib-infection in children below three years of age has decreased considerably.

J Chemother, 1995 May, 7 Suppl 1, 16 - 20
Amoxicillin/clavulanic acid vs cefetamet pivoxil in the treatment of acute exacerbation of chronic bronchitis (AECB) in adults; Behler PG et al.; In this open comparative and prospective study 180 adults of either sex were randomised to treatment with either amoxicillin/clavulanic acid (AMC) 500/125mg tid or cefetamet pivoxil (CAT) 500mg bid for 7 days . Demographic data and assessable findings were similar in both groups . Clinical outcomes of 169 assessable patients showed high efficacy of both drugs: 92% with AMC and 96% with CAT . Bacteriological response rates were equivalent in 141 evaluable cases: 84% vs . 89%, respectively . Baseline susceptibility testing (DIN) revealed a notable number of Haemophilus species either intermediately susceptible or resistant to AMC . Gastrointestinal disorders predominated among the adverse events with diarrhea occurring nearly twice as often in the AMC group . CAT is an effective and safe alternative option in the treatment of AECB in adults . The advantage of CAT is its enhanced activity against gram-negative bacteria . It is well tolerated.

Rev Inst Med Trop Sao Paulo, 1995 May-Jun, 37(3), 257 - 60
Bacterial antigen detection in cerebrospinal fluid by the latex agglutination test; Landgraf IM et al.; Eighty purulent cerebrospinal fluid (CSF) samples from patients with clinical evidence of meningitis were studied using the Directigen latex agglutination (LA) kit to determine the presence of bacterial antigen in CSF . The results showed a better diagnostic performance of the LA test than bacterioscopy by Gram stain, culture and counterimmunoelectrophoresis (CIE), as far as Neisseria meningitidis groups B and C, and Haemophilus influenzae type b are concerned, and a better performance than bacterioscopy and culture considering Streptococcus pneumoniae . Comparison of the results with those of culture showed that the LA test had the highest sensitivity for the Neisseria meningitidis group C . Comparing the results with those of CIE, the highest levels of sensitivity were detected for N . meningitidis groups B and C . Regarding specificity, fair values were obtained for all organisms tested . The degree of K agreement when the LA test was compared with CIE exhibited better K indices of agreement for N . meningitidis groups B and C.

J Pediatr, 1995 May, 126(5 Pt 1), 799 - 806
Bacteriologic failure of amoxicillin-clavulanate in treatment of acute otitis media caused by nontypeable Haemophilus influenzae; Patel JA et al.; OBJECTIVE: To evaluate the rate of bacteriologic failure of amoxicillin-clavulanate in the treatment of acute otitis media (AOM) and to identify the risk factors associated with failure . METHODS: Ninety-nine subjects (mean age, 21.4 months) with AOM were treated with amoxicillin-clavulanate in two prospective study trials that compared efficacy of two experimental antibiotics with amoxicillin-clavulanate . Tympanocentesis for microbiologic studies was performed in all subjects at enrollment; at 3 to 6 days, during amoxicillin-clavulanate therapy; and at other times when clinically indicated . The subjects were followed up for 1 month . Clinical, bacteriologic, and virologic characteristics of the subjects were analyzed . RESULTS: Bacteriologic failure of treatment occurred in none of 39 subjects (0%) with Streptococcus pneumoniae, two of 25 (8%) with Moraxella catarrhalis, and 11 of 29 (38%) with nontypeable Haemophilus influenzae (NTHi) infection . The failure rate for NTHi was higher than that for other pathogens (p = 0.0007) and was increased when compared with the preceding study period (p = 0.017) . Bacteriologic failure was also associated with clinical failure (p = 0.041) . In subjects with AOM caused by NTHi the rates of adequate drug compliance were comparable in both success and failure groups . Antimicrobial susceptibility testing by minimum inhibitory concentration and minimum bactericidal concentration (MIC/MBC) assays showed that amoxicillin-clavulanate resistance was not significantly associated with bacteriologic failure of treatment . However, in two subjects, MIC/MBC of the NTHi isolates during therapy were higher than MIC/MBC of the isolates before therapy; these strains of isolates pretherapy and during therapy were discordant as determined by outer membrane protein analysis . The bacteriologic failure rate was higher in nonwhite boys (p = 0.026) and in subjects with a history of three or more previous episodes of AOM (p = 0.008) . Other factors such as age, bilaterality of disease, polymicrobial infection, and biotype pattern of NTHi were not associated with treatment failure . When children with adequate drug compliance were analyzed separately, only those with concomitant viral infection of the nasopharynx or middle ear were found to be at an increased risk of bacteriologic failure of treatment (p = 0.04) . CONCLUSIONS: The bacteriologic failure rate of amoxicillin-clavulanate therapy for AOM caused by NTHi was higher in the current study period than in the preceding period . Factors contributing to treatment failure were race, gender, proneness to otitis, and concomitant viral infection.

J Infect Dis, 1995 May, 171(5), 1217 - 22
Response of recent human immunodeficiency virus seroconverters to the pneumococcal polysaccharide vaccine and Haemophilus influenzae type b conjugate vaccine; Weiss PJ et al.; Antibody responses in recent human immunodeficiency virus (HIV) seroconverters to 2 vaccines were studied . Twenty patients infected with HIV for < 18 months and 15 HIV-seronegative controls were vaccinated with the 23-valent pure polysaccharide pneumococcal vaccine and the Haemophilus influenzae type b (Hib) capsular polysaccharide diphtheria CRM197 protein toxoid conjugate vaccine in separate arms . Despite increased levels of total serum IgG, recent seroconverters and controls showed similar specific IgG responses for 6 of 7 antigens . Baseline levels were equivalent in both groups, as were peak levels of IgG at 1 month to conjugated polysaccharide (Hib), delayed-type hypersensitivity, and pneumococcal capsular serotypes 4, 6B, 12F, and 14 . At 6 months, IgG levels were similar for 4 of 7 antigens . Antibody responses to pure pneumococcal capsular polysaccharides and to a protein recall antigen were most often similar among recent seroconverters and seronegative controls . Both total levels and fold-rises of IgG to the Hib conjugate were similar in the 2 groups . Immunization of HIV-infected patients soon after seroconversion rather than later appears to improve antibody responses.

J Bacteriol, 1995 May, 177(10), 2950 - 2
HpaII methyltransferase is mutagenic in Escherichia coli; Bandaru B et al.; A genetic reversion assay to study C-to-T mutations within CG sites in DNA is described . It was used to demonstrate that the presence of HpaII methyltransferase (MTase) in Escherichia coli causes a substantial increase in C-to-T mutations at CG sites . This is similar to the known mutagenic effects of E . coli MTase Dcm within its own recognition sequence . With this genetic system, a homolog of an E . coli DNA repair gene in Haemophilus parainfluenzae was tested for antimutagenic activity . Unexpectedly, the homolog was found to have little effect on the reversion frequency . The system was also used to show that HpaII and SssI MTases can convert cytosine to uracil in vitro . These studies define 5-methylcytosine as an intrinsic mutagen and further elaborate the mutagenic potential of cytosine MTases.

J Bacteriol, 1995 May, 177(10), 2644 - 53
A gene cluster involved in the utilization of both free heme and heme:hemopexin by Haemophilus influenzae type b; Cope LD et al.; The utilization of heme bound to the serum glycoprotein hemopexin by Haemophilus influenzae type b (Hib) strain DL42 requires the presence of the 100-kDa heme:hemopexin-binding protein encoded by the hxuA gene (M . S . Hanson, S . E . Pelzel, J . Latimer, U . Muller-Eberhard, and E . J . Hansen, Proc . Natl . Acad . Sci . USA 89:1973-1977, 1992) . Nucleotide sequence analysis of a 5-kb region immediately upstream from the hxuA gene revealed the presence of two genes, designated hxuC and hxuB, which encoded outer membrane proteins . The 78-kDa HxuC protein had similarity to TonB-dependent outer membrane proteins of other organisms, whereas the 60-kDa HxuB molecule most closely resembled the ShlB protein of Serratia marcescens . A set of three isogenic Hib mutants with cat cartridges inserted individually into their hxuA, hxuB, and hxuC genes was constructed . None of these mutants could utilize heme:hemopexin . The hxuC mutant was also unable to utilize low levels of free heme, whereas both the hxuA and hxuB mutants could utilize free heme . When the wild-type hxuC gene was present in trans, the hxuC mutant regained its ability to utilize low levels of free heme but still could not utilize heme:hemopexin . The hxuA mutant could utilize heme:hemopexin when a functional hxuA gene from a nontypeable H . influenzae strain was present in trans . Complementation analysis using this cloned nontypeable H . influenzae hxuA gene also indicated that the HxuB protein likely functions in the release of soluble HxuA from the Hib cell . These studies indicate that at least two and possible three gene products are required for utilization of heme bound to hemopexin by Hib strain DL42.

Arch Pediatr Adolesc Med, 1995 May, 149(5), 537 - 40
Epidemiology, etiology, and clinical features of septic arthritis in children younger than 24 months; Yagupsky P et al.; OBJECTIVE: To examine the incidence, etiology, and clinical features of septic arthritis in patients younger than 24 months . DESIGN: Retrospective, 1988 through 1993 period, chart review-based survey . PATIENTS: All children with bacteriologically proved septic arthritis that was diagnosed at a medical center serving southern Israel (population 320,000) . Septic arthritis was defined by clinical evidence of joint inflammation and a positive synovial fluid or blood culture, antigen detection test, or a standard tube agglutination titer of 160 or greater for Brucella species . INTERVENTIONS: None . RESULTS: During the 6-year period, 40 children had septic arthritis diagnosed . Twenty-six (65%) were male . The annual incidence of septic arthritis was 37.1 per 100,000 . The two most common organisms isolated were Kingella kingae in 19 (48%) and Haemophilus influenzae type b in eight (20%) . The clinical presentation was frequently mild: a body temperature of less than 38.3 degrees C was recorded in 14 (35%) of 40 children, leukocyte count of less than 15 x 10(9)/L in 13 (34%) of 38, and erythrocyte sedimentation rate of less than 30 mm per hour in four (11%) of 35 . In eight (36%) of 22 patients, less than 50 x 10(9)/L leukocytes were counted in the synovial fluid . CONCLUSIONS: The diagnosis of septic arthritis in young children requires a high index of suspicion, and the disease cannot be excluded on the basis of lack of fever or normal results of laboratory tests . Kingella kingae appears to be the most common cause of septic arthritis in patients younger than 24 months, although confirmatory studies from other geographic areas are still needed.

Infect Immun, 1995 May, 63(5), 2082 - 6
Molecular cloning of Proteus mirabilis uroepithelial cell adherence (uca) genes; Cook SW et al.; Proteus mirabilis bacteria are a common cause of hospital-acquired urinary tract infection . In a previous study, we described a P . mirabilis fimbrial protein, UCA, that adhered to human uroepithelial cells . Genes sufficient for expression of UCA adherence were cloned into Escherichia coli K-12 . E . coli bacteria that contained the uca recombinant plasmid adhered to human uroepithelial cells . In addition, the ucaA gene encoding the structural component of UCA pili was subcloned, and its DNA sequence was determined . Amino acid sequence homology (30 to 50%) was found between mature UcaA protein and pilins from pathogenic bacteria representing several genera, including E . coli F17, G, and type 1C pilins, Haemophilus M43 pilin, and a Bordetella pilin.

Infect Immun, 1995 May, 63(5), 2012 - 20
Inducible immunity with a pilus preparation booster vaccination in an animal model of Haemophilus ducreyi infection and disease; Desjardins M et al.; Using the temperature-dependent rabbit model of Haemophilus ducreyi infection as a quantitative virulence assay, we tested the abilities of two bacterial antigen preparations to induce protection against subsequent infection and disease . Lipooligosaccharide (LOS) and a pilus preparation were purified from H . ducreyi 35000 and were used in a booster immunization procedure . The serologic response to each immunogen was monitored by enzyme immunoassay . H . ducreyi virulence was assayed by intraepithelial inoculation and subsequent measurement of disease for homologous strain 35000 or clinical isolate RO-34 . LOS and the pilus preparation induced humoral responses . The kinetics of the LOS antibody response suggest a type 1 T-independent response, whereas the pilus preparation induced an anamnestic response . An inoculum of 10(5) CFU of H . ducreyi 35000 or RO-34 consistently produced ulcerative chancroidal lesions in naive rabbit controls . Immunization with LOS did not modify the virulence of H . ducreyi 35000 . Immunization with the strain 35000 pilus preparation significantly reduced the severity of disease and the duration of infection and disease compared with controls, with either homologous or heterologous strain infection . The histology of lesions from pilus preparation-vaccinated rabbits compared with that of lesions from controls revealed accelerated lymphoid cell recruitment, more prominent plasma cell infiltrate, and reduction in subsequent histiocytic infiltration . We conclude that both LOS and the pilus preparation are immunogenic and that the latter induces homologous and heterologous strain protection in this animal model of infection and disease.

Infect Immun, 1995 May, 63(5), 1906 - 13
Human immunoglobulin M paraproteins cross-reactive with Neisseria meningitidis group B polysaccharide and fetal brain; Azmi FH et al.; Three hundred fifty-nine serum samples from patients with immunoglobulin M (IgM) or IgG monoclonal gammopathies were tested for binding to the capsular polysaccharide (PS) of Neisseria meningitidis group B (MenB PS, poly-alpha{2-->8}-N-acetylneuraminic acid) . Of 159 IgM paraproteins, 7 (4.4%) were positive, compared with 0 of 200 IgG paraproteins (P < 0.05) . Since MenB PS reactivity was limited to the IgM paraproteins, the 159 IgM paraproteins were tested by enzyme-linked immunosorbent assay (ELISA) for reactivity with seven other bacterial PSs . None reacted with meningococcal A or C, Haemophilus influenzae type b, or Streptococcus pneumoniae type 3, 6, 14, or 23 PS . The specificity of the MenB PS-reactive antibodies was confirmed by demonstration of binding to N . meningitidis group B cells but not to a capsular PS-deficient mutant and by specific inhibition of binding to solid-phase MenB PS by soluble MenB PS in an ELISA . Five of five antibodies tested protected infant rats from bacteremia caused by Escherichia coli K1, an organism with a PS capsule that also is composed of poly-alpha{2-->8}-N-acetylneuraminic acid . Each of the seven MenB PS-reactive paraproteins had autoantibody activity as defined by binding to homogenates of calf brain in a radioimmunoassay . For six of the seven antibodies, binding to calf brain was inhibited by the addition of soluble MenB PS . Thus, approximately 4% of human IgM paraproteins have autoantibody activity to poly-alpha{2-->8}-N-acetylneuraminic acid, an antigen expressed in fetal brain and cross-reactive with the MenB capsular PS . The reason for this skewing of the IgM paraprotein repertoire toward reactivity with poly-alpha{2-->8}-N-acetylneuraminic acid antigenic determinants is unknown.

Infect Immun, 1995 May, 63(5), 1754 - 61
Use of tissue culture and animal models to identify virulence-associated traits of Haemophilus ducreyi; Alfa MJ et al.; To identify virulence-associated properties of Haemophilus ducreyi, 34 strains of this sexually transmitted pathogen were evaluated for in vitro phenotypic characteristics of potential relevance to chancroid pathogenesis and for their ability to produce lesions in the temperature-dependent animal model for chancroid . Of the 34 strains tested, all but three produced a cytopathic effect on human foreskin fibroblasts (HFF) and all but six strains formed large microcolonies on HFF monolayers . A subset of 12 selected strains underwent more extensive analyses and, when evaluated for both their cytadherence kinetics and growth in the presence of HFF monolayers, it was found that several of these strains had a very limited ability to attach to HFF cells . When the same 12 strains were tested in the temperature-dependent rabbit model, only the seven strains which were positive in all of these in vitro-based tests readily produced lesions . In contrast, the five strains that were noted to be deficient in one or more of the phenotypic characteristics scored in the in vitro systems did not produce lesions . This association between the traits measured in vitro and the ability to produce dermal lesions was significant (P = 0.0012) . These results suggest that in vitro behavior may be used to predict the virulence potential of H . ducreyi strains . Moreover, the phenotypic characteristics described in this study are appropriate focal points for efforts to determine the molecular basis of the virulence of this pathogen.

Infect Immun, 1995 May, 63(5), 1631 - 6
Novel lipoprotein expressed by Neisseria meningitidis but not by Neisseria gonorrhoeae; Yang QL et al.; The ppk gene, which codes for the enzyme polyphosphate kinase in Neisseria meningitidis strain BNCV, is preceded by an open reading frame coding for a protein with a predicted size of 19.2 kDa with a typical lipoprotein signal sequence of 21 amino acids . The protein has significant homology to the N-terminal portion of an outer membrane protein from Haemophilus somnus (J . Won and R . W . Griffith, Infect . Immun . 61:2813-2821, 1993) . Sequencing of the same open reading frame from meningococcus strain M1080 predicted an almost identical protein . Antisera were raised against the lipoprotein, expressed in Escherichia coli as a fusion protein with glutathione S-transferase . The antisera reacted with meningococcal membrane fractions on a Western blot (immunoblot) but did not elicit complement-dependent bactericidal activity . Restriction enzyme digestion demonstrated conservation of this portion of the meningococcal and gonococcal chromosomes . However, antisera raised to the recombinant protein showed that the protein was absent from all strains of gonococcus tested . The sequences of the gene from several strains of Neisseria gonorrhoeae and N . meningitidis were compared and found to be almost identical, except that the coding sequences from all of the gonococcal strains were terminated prematurely as a result of a frameshift mutation . The significance of the remarkable conservation of these gonococcal genes is discussed.

J Infect, 1995 May, 30(3), 219 - 22
Expression of capsules by Haemophilus influenzae in mixed infections; Brook I et al.; The pathogenicity of eight clinical isolates of non-type b Haemophilus influenzae was investigated by inoculating them subcutaneously into mice, alone or mixed with viable or non-viable bacteria of certain other species . Three of the H . influenzae isolates were non-capsulated while five were slightly capsulated (less than 1% of organisms had capsules) . The other strains of bacteria tested were four isolates of capsulated and four isolates of non-capsulated pigmented strains of Prevotella sp . and Porphyromonus sp . as well as a capsulate Klebsiella pneumoniae ("helpers") . None of the non-capsulated strains induced an abscess when inoculated alone . Following co-inoculation of viable or non-viable "helpers" with H . influenzae, abscesses were formed in all instances in which the "helper" had a capsule . Profusely capsulated cells of H . influenzae were recovered, however, only from abscesses induced with the five slightly capsulated strains of H . influenzae . These capsulated organisms were found serologically to be of type b and induced abscesses when inoculated alone . Our findings illustrate the ability of non-capsulated strains of H . influenzae to produce progeny of capsulated type b organisms after co-inoculation with certain other species.

J Hosp Infect, 1995 May, 30(1), 31 - 7
The relationship between intraoperative contamination of the lower respiratory tract and postoperative chest infection; Morran GG et al.; The relationship between intraoperative contamination of the lower respiratory tract and postoperative chest infection was studied in 193 patients undergoing biliary tract surgery . During surgery, sputum was obtained from the lower respiratory tract for bacteriological culture . The diagnosis of postoperative pulmonary complications was based on clinical criteria, supported by the pattern of sequential blood gas changes in the postoperative period . Chest infection was present in 30% of patients who harboured Haemophilus species in their sputum at the time of surgery compared with 10% of those with negative cultures . Contamination of the lower respiratory tract at operation by Haemophilus sp . is associated with development of postoperative chest infection.

Clin Diagn Lab Immunol, 1995 May, 2(3), 286 - 90
A rapid and sensitive chemiluminescence assay for evaluation of functional opsonic activity of Haemophilus influenzae type b-specific antibodies; Ojo-Amaize EA et al.; Luminol-enhanced chemiluminescence (CL) of heterologous neutrophils was used to assess the capacity of a 1-ng/ml concentration of Haemophilus influenzae type b (Hib)-specific antibodies to induce opsonization of Hib with autologous heat-inactivated sera from children immunized with Hib capsular polysaccharide-polyribosylribitolphosphate (Hib-PRP) conjugate vaccine . Serum samples from 15 of 36 children (42%) vaccinated with Hib-PRP conjugate vaccine had protective levels of Hib-specific antibodies of > or = 1,000 ng/ml . Ten of these 15 (67%) had poor or nonfunctional opsonic activity . Of the 10 children whose sera lacked opsonic activity, 5 (50%) presented with recurrent Hib infection . In contrast, none of the sera of 20 healthy adults lacked opsonic capability . CL intensity was proportional to the concentration of anti-Hib antibodies used for opsonization . Furthermore, the titers of Hib-PRP-specific antibody in children and adults did not correlate with opsonic activity . These results suggest that luminol-enhanced CL as described here with minute concentrations of antibody for opsonization can be used to assess functional capacity of anti-Hib antibodies after vaccination or natural infection in the evaluation of patients with recurrent infections.

Clin Diagn Lab Immunol, 1995 May, 2(3), 272 - 6
Effect of age on concentrations of serum antibodies to viral, bacterial, and food antigens in elderly Swiss people; Brussow H et al.; Serum antibody concentrations to two viral, five bacterial, and two food antigens were investigated in 307 elderly Swiss subjects, and the hypothesis of whether serum antibody titers decreased with age was tested . The cross-sectional part of the study consisted of 216 unselected consecutive patients hospitalized in one geriatric hospital . The patients were divided into two age groups (65 to 84 and 85 to 102 years old), and their antibody titers were compared . No age-related decreases in antibody titers were observed . The members of the two age groups were well matched for medical diagnosis and nutritional and inflammatory status . The prospective part of the study consisted of 91 healthy elderly subjects living in the community; they were 71 to 76 years old when they were enrolled in the study . Their serum antibody status was measured at the beginning of the study and 4 years later . We observed a significant decrease in diphtheria antitoxin levels and a significant increase in antibody titer to the capsular polysaccharide of Streptococcus pneumoniae . No change in antibody titer to rotavirus, respiratory syncytial virus, lipopolysaccharide of Escherichia coli, C polysaccharide of S . pneumoniae, or the polyribosyl-ribitol phosphate of Haemophilus influenzae was observed . Thus, no signs of B-cell immunosenescence were seen in these two groups of elderly Swiss people.

Eur Respir J, 1995 May, 8(5), 709 - 14
Interaction of fimbriated and nonfimbriated strains of unencapsulated Haemophilus influenzae with human respiratory tract mucus in vitro; Barsum W et al.; Adherence to mucus may influence bacterial colonization of the respiratory tract . Clinical isolates of nontypable Haemophilus influenzae (NTHi) from the respiratory tract are often fimbriated . We wondered whether fimbriated strains have a different adherence from related nonfimbriated strains . A microtitre plate assay has been developed to study adherence of nontypable H . influenzae to mucus . Wells were coated by incubation either with sol phase of sterile mucoid secretions or with purified preparations of mucins . Two laboratory pairs of fimbriated (F+) and nonfimbriated (F-) nontypable H . influenzae, and six fresh clinical isolates of fimbriated nontypable H . influenzae each with nonfimbriated partners derived by serial passage on agar, were cultured to mid-log phase, washed, and then added to the wells . They were then incubated at 37 degrees C for 30 min before washing to remove unbound bacteria . Adherent bacteria were desorbed by agitation with 0.5% Tween 80 and a viable count performed . The two fimbriated laboratory strains (n = 12 and n = 17), and 5 of the 6 fimbriated clinical isolates were more adherent to sol phase than their respective nonfimbriated partners . Two nonfimbriated clinical isolates were more adherent to plastic than their fimbriated partners . A fimbriated laboratory strain was more adherent than its nonfimbriated partner both to a purified preparation of high molecular mass mucin and to the glycopeptide fraction of the same . We conclude that fimbriated strains of nontypable H . influenzae have increased adherence to sol phase of mucus and purified human respiratory tract mucin . The interactions of fimbriae with mucus are likely to be complex, and may involve both nonspecific and specific interactions.

Pediatr Infect Dis J, 1995 May, 14(5), 445 - 9
Present and future challenges of immunizations on the health of our patients; Gershon AA; A recent analysis demonstrated a change in incidence approaching 100% for diseases against which we routinely immunize in the United States . At present, measles, mumps, rubella, invasive Haemophilus disease, poliomyelitis, diphtheria and tetanus are well-controlled but not eliminated . Diseases that now pose special problems include pertussis, hepatitis A and B and varicella . The incidence of pertussis surged in 1994, possibly in part because of waning immunity in the immunized population . Acellular pertussis vaccines are available for booster doses in children but are not now recommended for adults . Licensure of acellular pertussis vaccines for primary immunization of infants is eagerly awaited . Recombinant hepatitis B vaccine has been licensed for more than 10 years but there has been little change in disease incidence in the United States . Routine immunization of infants is now recommended but concerns exist about cost and persistence of immunity into adolescence . Inactivated hepatitis A vaccines appear to be highly effective in preventing clinical hepatitis and controlling epidemics . Potential target populations include military personnel, day-care attendees and travelers . Hepatitis A vaccine may be recommended for all children after approval by the United States Food and Drug Administration and if a combination vaccine becomes available . A live, attenuated varicella vaccine developed in 1974 and unlicensed in the United States is safe and highly effective in preventing varicella in healthy and immunocompromised populations . It also appears to reduce subsequent development of herpes zoster . Vaccines against pneumococci (conjugate vaccine), respiratory syncytial virus, rotavirus, tuberculosis and human immunodeficiency virus are needed . Research and technology to develop these vaccines must be developed, and efficient delivery mechanisms must be created and implemented.

Pediatr Infect Dis J, 1995 May, 14(5), 420 - 3
Resistance among problem respiratory pathogens in pediatrics; Doern GV; During the past two decades, the prevalence of beta-lactamase production with nontypable strains of Haemophilus influenzae has increased to about 35% . Fortunately, rates of resistance to other oral antimicrobials have not developed at a comparable pace . Amoxicillin/clavulanate, cefuroxime and cefpodoxime remain nearly uniformly active whereas rates of resistance to tetracycline, trimethoprim/sulfamethoxazole, chloramphenicol, cefaclor, loracarbef, cefprozil, azithromycin and clarithromycin remain low (1 to 5%) . Virtually all clinical isolates of Moraxella catarrhalis produce beta-lactamase and are probably resistant to ampicillin and amoxicillin . However, alternative oral antimicrobials are almost always active . A compelling problem facing pediatricians today is the emergence of penicillin resistance with clinical isolates of Streptococcus pneumoniae . Currently, 15 to 25% of pneumococcal isolates in the United States have either intermediate (10 to 20%) or complete (3 to 5%) penicillin resistance caused by alterations in penicillin-binding proteins . Loss of activity of other beta-lactams is observed with penicillin-resistant S . pneumoniae . Third generation cephalosporins retain sufficient activity to warrant use in selected pneumococcal infections, even those caused by completely penicillin-resistant strains . Unfortunately, strains of S . pneumoniae with further alterations in penicillin-binding proteins have emerged such that even extended spectrum third generation cephalosporins lack activity . Rates of resistance to non-beta-lactam agents are also changing . The consequence of these changing patterns of resistance is that therapeutic options for pneumococcal infections in some patients are becoming increasingly limited.

Pediatr Infect Dis J, 1995 May, 14(5), 415 - 9
Antimicrobial therapy issues facing pediatricians; Klein JO; In the field of infectious diseases, the emergence of new pathogens or old diseases in newly recognized forms; changing virulence of pathogens; changing patterns of antimicrobial susceptibility; new diagnostic techniques, drugs or vaccines; changing concepts of chemoprophylaxis; controversies about medical vs . surgical techniques; and the challenge of care of children with infectious diseases within new guidelines of managed care are recently identified areas of change . The increased resistance of Streptococcus pneumoniae to many commonly used antimicrobials and the increased proportion of beta-lactamase-producing nontypable Haemophilus influenzae and Moraxella catarrhalis concern many practitioners . The decreased antibiotic susceptibility of S . pneumoniae is a relatively new phenomenon in the United States . Optimal therapy for mild, moderate or severe pneumococcal disease is dependent on current local susceptibility patterns . Group A streptococci are uniformly susceptible to readily achieved concentrations of all penicillins and cephalosporins . However, recent clusters of cases of rheumatic fever, increased recognition of toxic shock syndrome and bacteremic and localized severe pneumococcal disease have increased concern about the changing ecology of the Streptococcus and the implications for therapy . Finally recognition that many children with acute bacterial otitis media have resolution of disease without use of antimicrobial agents has led to more rigorous study designs for evaluating new drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Pediatr Infect Dis J, 1995 May, 14(5), 350 - 4
The immunogenicity of Haemophilus influenzae type b conjugate (HbOC) vaccine in human immunodeficiency virus-infected and uninfected infants; Kale KL et al.; Enzyme-linked immunosorbent assay polyribosyl ribitol phosphate (PRP) antibody responses to Haemophilus influenzae type b conjugate vaccine (HbOC) given at 2, 4 and 6 months of age were retrospectively compared in 23 human immunodeficiency virus (HIV) and 24 non-HIV-infected infants . HIV-infected infants were divided into those who were P1 (asymptomatic) or P2 (symptomatic) by 1 year of age . The P2 group was further divided into P2A (mildly symptomatic) and > P2A (rapidly symptomatic) by 1 year of age . The post-third HbOC dose geometric mean antibody titer to PRP was significantly lower in 12 P2 infants (0.43 microgram/ml) than either the 11 P1 infants (5.03 micrograms/ml, P < 0.05) or the 24 non-HIV infected infants (3.43 micrograms/ml, P < 0.05) . Within the P2 group, the geometric mean antibody titer to PRP was significantly higher in 5 P2A infants (1.63 micrograms/ml) compared with 7 infants who were > P2A (0.17 microgram/ml, P < 0.05) . After the third HbOC dose, PRP antibody titers were > or = 1.0 micrograms/ml for 4 of 12 P2 compared with 9 of 11 P1 infants (P < 0.05) . Within the P2 group, PRP antibody titers were > 1.0 micrograms/ml for 4 of 5 P2A compared to 0 of 7 infants who were > P2A (P < 0.05) . HIV-infected infants with PRP antibody titers > or = 1.0 micrograms/ml after the third HbOC dose had significantly higher mean CD4 counts (2842 cells/mm3) at the time of the third HbOC dose than those with lower PRP titers (1655 cells/mm3) (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Jpn J Antibiot, 1995 May, 48(5), 602 - 9
{Antibacterial activities of cefmenoxime against recent fresh clinical isolates from patients in sinusitis}; Yokota N et al.; In order to evaluate antimicrobial activity of cefmenoxime (CMX), minimum inhibitory concentrations (MICs) of CMX and control drugs were determined against clinical isolates from patients of sinusitis that were obtained in our laboratory from October of 1993 to March of 1994 . The results are summarized as follows; 1 . CMX showed strong antimicrobial activities against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella subgenus Branhamella catarrhalis that were 3 major aerobic bacteria from sinusitis . Antimicrobial activities of CMX against benzylpenicillin (PCG)-insensitive S . pneumoniae (PISP) and PCG-resistant S . pneumoniae (PRSP) were stronger than those of ampicillin (ABPC), and these strong activities suggested that CMX might have strong antimicrobial activities against beta-lactamase producing H . influenzae and M . (B.) catarrhalis . 2 . Antimicrobial activities of CMX against microaerophiles, Streptococcus constellatus, Streptococcus intermedius and Gemella morbillorum and against Peptostreptococcus spp., from chronic sinusitis and odontogenic maxillary sinusitis, were stronger than those of most of the control drugs . 3 . The MIC90's of CMX against isolates from patients of sinusitis were < or = 0.025-0.39 micrograms/ml . These values were lower than transitional concentrations in mucous membrane of maxillary sinus obtained when "1% CMX nasal solution" was used with nebulizer . It appears likely that sufficient concentrations exceeding MICs against main organisms would be obtained by nebulizer treatment using CMX nasal solution.

Clin Infect Dis, 1995 May, 20(5), 1381 - 3
Haemophilus paraphrophilus endocarditis: case report and review; Coll-Vinent B et al.; Endocarditis due to Haemophilus paraphrophilus is an uncommon disease . We report a case of H . paraphrophilus endocarditis with embolic complications in which the causative organism was resistant to beta-lactam antibiotics . Before April 1994, 16 cases of H . paraphrophilus endocarditis had been reported . Infection by this organism usually affects a previously damaged mitral valve . We emphasize the fastidiousness of the organism and the high incidence of embolic complications, which determine the outcome . To our knowledge we describe the first patient with endocarditis due to beta-lactam-resistant H . paraphrophilus.

Clin Infect Dis, 1995 May, 20(5), 1164 - 8
A single daily dose of ceftriaxone for bacterial meningitis in adults: experience with 84 patients and review of the literature; Cabellos C et al.; Although the pharmacokinetics of ceftriaxone allows its administration in a single daily dose, this practice is not standard in the treatment of bacterial meningitis . Herein, we review our experience and that of other investigators with this mode of therapy . We used a single daily dose of ceftriaxone (50 mg/{kg.d}; maximum, 4 g/d) for the treatment of bacterial meningitis in 84 adult patients . Meningitis was due to Neisseria meningitidis in 34 cases, to Streptococcus pneumoniae in 25, to Escherichia coli in three, to Klebsiella pneumoniae in two, to Haemophilus influenzae in two, to viridans streptococci in two, and to an unknown agent in 16 . Eleven patients died, for an overall mortality of 13%; therapy failed in three additional cases . The mean trough levels of ceftriaxone in cerebrospinal fluid was 3.5 micrograms/mL; the median trough bactericidal titer at this site was 1:128 . Both our experience and that in the literature suggest that a single daily dose is optimal when ceftriaxone is used for the treatment of bacterial meningitis.

Arch Dis Child, 1995 May, 72(5), 432 - 4
Urinary excretion of cortisol after immunisation; Westaway J et al.; Urinary cortisol excretion and rectal temperature were measured in 66 infants before and after immunisation against diphtheria, tetanus, pertussis, and Haemophilus influenzae type b . Immunisation produced a significant increase of rectal temperature the next night at all ages . Infants without an adult-like night time body temperature pattern had a significant increase in urinary cortisol excretion night and morning after immunisation . Once an adult-like night time body temperature pattern developed immunisation no longer significantly raised urinary cortisol output.

Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi, 1995 May-Jun, 36(3), 164 - 9
IgG subclasses in childhood infections; Bradwell AR; Selective IgG subclass (IgGSc) deficiencies are frequently found in association with recurrent infections in childhood . IgG1 deficiency is the most severe and is associated with features typical of panhypogammaglobulinaemia . Immunoglobulin replacement therapy is usually required . IgG2 deficiency is associated with recurrent infections with encapsulated bacteria such as Haemophilus influenzae and Streptococcus pneumoniae . IgG2 deficiency may be transient in children under five years of age and patients improve with antibiotics and immunisation . IgG3 and IgG4 deficiency are commonly found in children with recurrent infections and may indicate a disordered immune system since absence of these antibodies alone appears insufficient to cause symptoms . Children may also have selective IgGSc deficiencies in the absence of recurrent infections . This is explained by compensatory factors in other parts of the immune system . Measurement of IgGSc levels should be based on highly specific polyclonal antisera which show no IgGSc cross-reactivity . Most monoclonal antibodies are unsatisfactory since allotypes are detected variably, leading to excess reporting of IgGSc deficiencies and Mabs cannot be used for nephelometric or turbidimetric methods.

J Clin Microbiol, 1995 May, 33(5), 1426 - 7
Evaluation of novel vancomycin-containing medium for primary isolation of Kingella kingae from upper respiratory tract specimens; Yagupsky P et al.; A new selective medium (BAV), consisting of trypticase agar with 5% sheep hemoglobin and 2 micrograms of vancomycin per ml, was compared with the routine blood-agar medium for the primary isolation of Kingella kingae from upper respiratory specimens from a population of young children . Infection was detected by the BAV medium in 43 of 44 (98%) cultures positive for K . kingae, and detection of the organism was facilitated by inhibition of gram-positive flora . Infection was detected in only 10 of 44 (23%) positive cultures by the blood-agar medium, and plates were usually covered by abundant normal flora, making the recognition of K . kingae much more difficult . Challenge of the medium with different organisms of respiratory origin showed that the BAV medium was inhibitory for gram-positive cocci and Haemophilus influenzae but that it supported growth of eight K . kingae strains isolated from patients with invasive infections . The new medium appears to be a useful epidemiological tool for studying the respiratory carriage of K . kingae.

J Clin Microbiol, 1995 May, 33(5), 1174 - 9
PCR amplicon restriction endonuclease analysis of the chromosomal dhps gene of Neisseria meningitidis: a method for studying spread of the disease-causing strain in contacts of patients with meningococcal disease; Kristiansen BE et al.; We tested two sets of primers derived from the dhps gene of Neisseria meningitidis for the amplification of meningococcal DNA by PCR . Both the NM1-NM6 primers and the NM3-NM6 primers amplified dhps DNA from all of the meningococci included in the study, resulting, in most cases, in amplicons of 0.70 and 0.23 kb, respectively . Also, dhps DNAs of N . gonorrhoeae and some commensals were amplified but Haemophilus influenzae, Streptococcus pneumoniae, and Escherichia coli DNAs were not . By PCR amplicon restriction endonuclease analysis (AREA) of the larger amplicon, we could differentiate between individual strains of N . meningitidis . Following two cases of meningococcal disease, we used PCR AREA to identify healthy contacts carrying the disease-causing strain . We conclude that PCR AREA is a useful method for meningococcal strain differentiation and that it has potential as a method for studying the spread of a disease-causing strain in an affected population . The method is quicker and easier to perform and interpret than chromosomal DNA fingerprinting.

Thorax, 1995 May, 50(5), 543 - 7
Aetiology of community-acquired pneumonia: a prospective study among adults requiring admission to hospital; Bohte R et al.; BACKGROUND--The prevalence of microorganisms causing community-acquired pneumonia in patients who required admission to hospital was investigated and the percentage of cases whose aetiology remained unknown due to the study design and logistical problems estimated . METHODS--Between January 1991 and April 1993 all patients with community-acquired pneumonia admitted to six hospitals were included in the study . Aetiological diagnosis, categorised as definite, probable and possible, was based on the results of routine microbiological and serological tests . RESULTS--Three hundred and thirty four patients with a median age of 65 (range 17-92) years were enrolled in the study . The diagnosis of community-acquired pneumonia was definite in 108 cases, and probable or possible in 73 and 27 cases, respectively, including dual infections . Streptococcus pneumoniae was the predominant pathogen (27%) followed by viruses and Haemophilus influenzae (both about 8%) and Mycoplasma pneumoniae (6%) . Chlamydia spp (3%) and Legionella pneumophila (2%) were less frequently detected . No diagnosis was made in 45% of the cases . With adjustment for anti-microbial therapy before admission and for other logistical considerations, it is estimated that the aetiology could have been ascertained in 65% of the cases . CONCLUSIONS--Streptococcus pneumoniae is the most frequently detected cause of community-acquired pneumonia . The inability to detect a micro-organism results mainly from the use of routine diagnostic tests and, to a lesser extent, from logistical problems or the use of antibiotics before admission.

J Antimicrob Chemother, 1995 May, 35(5), 681 - 6
The in-vitro activity of biapanem against 964 clinical isolates of aerobic bacteria; Raymond NJ et al.; The in-vitro susceptibilities of 964 clinical isolates of aerobic bacteria to biapenem (a novel carbapenem), imipenem, ceftazidime and ciprofloxacin were determined by an agar dilution method . Compared with imipenem, biapenem exhibited greater activity against aerobic Gram-negative bacilli, similar activity against Neisseria meningitidis, Neisseria gonorrhoeae and Haemophilus influenzae and less activity against Gram-positive cocci.

Diagn Microbiol Infect Dis, 1995 May-Jun, 22(1-2), 147 - 54
Review and reassessment of dosing schedules for cefotaxime in selected medical indications; Young LS; Cefotaxime, the first widely used "third-generation" cephalosporin, has established efficacy against a variety of serious bacterial pathogens . Some of the initial clinical studies in the United States using this agent employed large doses of the compound, up to 12 g/day, for adults . In contrast, however, initial European studies were largely with low doses of 1 to 2 g every 12 h . In the recent past, however, an effort has been made, both in the United States and in Europe to reevaluate the dosage of cefotaxime . In various clinical studies, lower doses of cefotaxime have been successfully employed for infections of the urinary tract, peritoneum, biliary tract, lung, and skin and soft tissues . The results of a number of these studies will be reviewed, including a large postmarketing surveillance study carried out in Germany during 1992 . The results suggest that cefotaxime doses as low as 1 g, at intervals as long as every 12 h, can be adequate for treatment of the most commonly encountered infections, such as those caused by some hemolytic streptococci, Staphylococcus aureus, Haemophilus spp., and enteric bacilli in nonimmunocompromised patients.

Diagn Microbiol Infect Dis, 1995 May-Jun, 22(1-2), 125 - 7
Update on the use of cefotaxime for pediatric meningitis in Portugal; Lecour H et al.; We treated 256 children who had identified bacterial meningitis with cefotaxime . Causative organisms were: Neisseria meningitidis in 108 cases, Streptococcus pneumoniae in 61, Haemophilus influenzae in 60, enteric Gram-negative bacilli in 21, and Staphylococcus spp . in six . Daily doses of cefotaxime were 150-200 mg/kg . A total of 240 patients (93.7%) were cured . In the cured patients, sterilization of cerebrospinal fluid was obtained in the first 72 h of treatment in 214 (80.0%) . Cefotaxime is an effective and safe drug for the treatment of childhood bacterial meningitis.

Diagn Microbiol Infect Dis, 1995 May-Jun, 22(1-2), 105 - 10
Cefotaxime use in pediatric infections; Dajani AS; Cefotaxime has been used extensively in many pediatric centers in the United States for the past 10 or more years . Its main usage has been for the treatment of various serious bacterial infections in pediatric patients, primarily meningitis and sepsis . It has also been used to treat intraabdominal, urinary tract, soft tissue, bone, and joint infections . Although there has been a marked reduction in the incidence of invasive Haemophilus influenzae type b infections following the introduction of effective vaccines, cefotaxime remains very useful against the other common pathogens causing serious infections in pediatric patients . The increasing number of pneumococci resistant to penicillin and third-generation cephalosporins has created a new challenge for the management of serious pneumococcal infections . In many institutions, cephalosporins in general have been overused and abused, resulting in the emergence of resistant organisms and an increasing burden on resources . The judicious use of cefotaxime and other cephalosporins should be emphasized.

J Clin Microbiol, 1995 May, 33(5), 1192 - 5
Long PCR-ribotyping of nontypeable Haemophilus influenzae; Smith-Vaughan HC et al.; PCR-ribotyping, a new typing method based on long PCR, has been developed for nontypeable Haemophilus influenzae (NTHi) . Ribosomal operons of NTHi were amplified by long PCR and were found to be highly polymorphic for internal HaeIII sites . The technique was applied to 49 isolates previously subjected to conventional ribotyping, and the two methods showed a high level of concordance for serial isolates from individual subjects . PCR-ribotyping provides a powerful new typing tool for strain characterization in epidemiological investigations of NTHi.

Ned Tijdschr Geneeskd, 1995 Apr 29, 139(17), 885 - 90
{Pediatric surveillance of invasive infections caused by Haemophilus influenzae type b in children in the period following introduction of vaccination}; Conyn-van Spaendonck MA et al.; OBJECTIVE . Evaluation of the effect of vaccination against Haemophilus influenzae type b (Hib) on the occurrence of invasive Hib infections in children since its introduction into the national immunization programme in April 1993 . DESIGN . Observational study . SETTING . Nationwide investigation . METHOD . Data collected through active surveillance of invasive Hib infections by paediatricians for the period from October 1993 to September 1994 (11 months) were compared with data from the meningitis surveillance by the Netherlands Reference Laboratory for Bacterial Meningitis . RESULTS . A total of 139 paediatric reports of invasive disease by H . influenzae concerned 57 cases of only meningitis, 35 of meningitis with sepsis, 2 of meningitis with arthritis, one of meningitis with arthritis and osteomyelitis, 34 of epiglottitis including one case with sepsis, 8 of only sepsis and 2 of only arthritis . All proven infections by Hib occurred in children who had not or incompletely been vaccinated . One child with sepsis had had three vaccinations and became ill five months later; the isolated bacterial strain was not serotyped . Typing was performed in only 80% of the isolates, of which 98% were of type b . Appropriate culturing and typing was often omitted in case of epiglottitis . CONCLUSION . The effect of vaccination against Hib became apparent in a small number of cases of invasive Hib disease reported by paediatricians; the peak incidence of meningitis no longer occurred in children under one year of age but in children aged one year . The paediatric surveillance described offers possibilities for monitoring Hib epidemiology.

Ned Tijdschr Geneeskd, 1995 Apr 29, 139(17), 880 - 4
{Absence of meningitis caused by Haemophilus influenzae type b in The Netherlands following twofold vaccination}; van Alphen L et al.; OBJECTIVE . To determine the two-year results of nationwide vaccination with Haemophilus influenzae type b (Hib) vaccine on the occurrence of Hib meningitis in the Netherlands . DESIGN . Retrospective controlled study . SETTING . The Netherlands . METHOD . Children born since April 1, 1993 are vaccinated at the age of 3, 4, 5 and 11 months to protect them from infections with Hib . The number of Hib meningitis patients in the period 1 April, 1993 to 1 April, 1995, among infants born in this period who were offered the Hib vaccine (study group), was compared with the number of Hib meningitis patients in the period 1 April, 1991 to 1 April, 1993 among children born in last-mentioned period (control group) . RESULTS . Twenty-one cases of meningitis by Hib were observed in the study group . Twelve children who, as a consequence of their age, had only been vaccinated once or not at all; 7 children were not vaccinated for several reasons . In addition one patient was infected by H . influenzae type f strain and one by a non-typable strain . In the control group 185 cases of Hib meningitis occurred . CONCLUSION . Hib meningitis was not observed among infants who had been vaccinated at least twice.

J Immunol, 1995 Apr 15, 154(8), 4195 - 202
Functional differences in idiotypically defined IgG1 anti-polysaccharide antibodies elicited by vaccination with Haemophilus influenzae type B polysaccharide-protein conjugates; Lucas AH et al.; We investigated the relationship between the form of the Haemophilus influenzae type B (Hib) polysaccharide (PS)-protein conjugate vaccine, Id expression, and Ab quality . Two post-vaccination pools were prepared from sera of infants vaccinated with either Hib PS oligomers coupled to CRM197, a mutant diphtheria toxin (HbOC), or with higher m.w . Hib PS coupled to an outer membrane protein complex of Neisseria meningitidis group B (Hib-OMP) . The mean anti-Hib PS Ab avidity of the serum pool from the infants vaccinated with HbOC was threefold higher than that of the pool from infants vaccinated with Hib-OMP . Using sequential immunoabsorption, three IgG1 idiotypically-defined anti-Hib PS fractions were isolated from each of the serum pools: Hibld-1, Hibld-2, and a Hibld-1/-2-depleted population, designated Hibld-0 . Hibld-1 and Hibld-2 are idiotypic markers for anti-Hib PS Abs expressing kappa II-A2 and lambda VII V regions, respectively . Hibld-1 anti-Hib PS Abs had significantly higher avidity, 2- to 19-fold higher in vitro bactericidal activity, and were more protective against Hib bacteremia in infant rats, than the respective Hibld-2 Abs isolated from each of the pools . Comparing the two vaccines, Hibld-1 anti-Hib PS Abs elicited by HbOC had significantly higher avidity and 10-fold higher bactericidal and rat protective activity than the Hibld-1 Abs elicited by Hib-OMP . These findings demonstrate that the molecular form of the Hib PS immunogen dictates both V region usage and quality of Ab function.

Gene, 1995 Apr 14, 156(1), 97 - 9
The sequencing of the 80-kDa D15 protective surface antigen of Haemophilus influenzae; Flack FS et al.; The 80-kDa D15 antigen (D-15-Ag) has previously been shown to be a target for protective immunity and conserved amongst typeable and nontypeable Haemophilus influenzae . Here, the gene encoding D-15-Ag is shown to encode a 797-aa polypeptide which, after cleavage of the predicted signal peptide, would have a molecular mass of 85,632 Da.

Proc Natl Acad Sci U S A, 1995 Apr 11, 92(8), 3616 - 20
Identification of a DNA transformation gene required for com101A+ expression and supertransformer phenotype in Haemophilus influenzae; Zulty JJ et al.; DNA sequencing, RNA mapping, and protein expression experiments revealed the presence of a gene, tfoX+, encoding a 24.9-kDa polypeptide, that is transcribed divergently from a common promoter region with the Haemophilus influenzae rec-1+ gene . H . influenzae strains mutant for tfoX failed to bind transforming DNA and were transformation deficient . Primer extension experiments utilizing in vivo total RNA from precompetent and competent H . influenzae cells demonstrated that transcription of tfoX+ increased immediately upon competence induction, suggesting that tfoX+ is an early competence gene . Similar experiments showed that the expression of the late competence-specific gene, com101A+, was tfoX+ dependent . Moreover, expression of plasmid-borne tfoX+ in H . influenzae resulted in constitutive competence . The addition of cyclic adenosine monophosphate (cAMP) to strains carrying a tfoX::lacZ operon fusion resulted in an immediate increase in beta-galactosidase activity that correlated with an increase in genetic transformability . Collectively, our results suggest that TfoX may play a key role in the development of genetic competence by regulating the expression of late competence-specific genes.

Scand J Immunol, 1995 Apr, 41(4), 324 - 30
Predominant V-region gene configurations in the human antibody response to Haemophilus influenzae capsule polysaccharide; Pinchuk GV et al.; The antibody response to Haemophilus influenzae type b polysaccharide (Hib PS) is known to be encoded by a few V-region genes . We have obtained four human monoclonal Hib PS antibodies from four healthy adult subjects immunized with diphtheria toxin-conjugated Hib PS vaccine . The VH gene segments that encode for these antibodies belong to the VH3 gene family, of which two are related to the V3-23 gene and two to the VH3b subfamily . Both hybridomas that express a V3-23-related gene use short D-segments (3 bp), the JH6 gene segment and a V kappa gene derived from the A2 germline gene . The two hybridomas that express VH3b genes use D-segments of conventional length (24-33 bp), the JH4 gene segment and a non-A2 V kappa gene . Comparison of our sequences with those reported by others suggests that the above patterns of V-region gene segment association exemplify two V-region gene configurations that are predominant in the Hib PS antibody response . The first configuration is reminiscent of antibodies produced by B-1 B cells while the second is more characteristic of antibodies produced by conventional B cells . The possibility that these two configurations, in fact, represent the products of two different B cell lineages remains to be elucidated.

J Bacteriol, 1995 Apr, 177(7), 1788 - 96
Genomic organization of the Klebsiella pneumoniae cps region responsible for serotype K2 capsular polysaccharide synthesis in the virulent strain Chedid; Arakawa Y et al.; The genomic organization of the chromosomal cps region that is responsible for capsular polysaccharide synthesis in Klebsiella pneumoniae Chedid (O1:K2) was investigated . Deletion analyses and Southern hybridization studies suggested that the central region of the cloned 29-kb BamHI fragment is indispensable for K2 capsular polysaccharide synthesis . The 24,329-bp nucleotide sequence of the Klebsiella cps region was determined and deposited in the EMBL and GenBank databases through DDBJ and assigned accession number D21242 . Nineteen possible open reading frames (ORFs) were identified in the sequenced area . Among them, 13 ORFs are very close to each other . Six of the 19 ORFs show considerable nucleotide sequence similarities to Salmonella typhimurium cpsG, cpsB, rfbP, and orf2.8, Escherichia coli gnd, and Haemophilus influenzae bexD, respectively . Moreover, the deduced amino acid sequence of the ORF10 product demonstrated a highly hydrophobic profile and showed putative membrane topology similarity to Rickettsia prowazekii ATP/ADP translocase . Nucleotide sequence similar to the sigma 54-dependent promoter, as well as the usual -35 and -10 sequences, were identified just upstream of ORF3, which is the first ORF in the polycistronic structure . Furthermore, a sequence (GGGCGGTAGCGT) found just downstream of the sigma 54-dependent promoter-like sequence was generally conserved among gene clusters implicated in cell surface polysaccharide synthesis, such as Salmonella rfb and viaB and E . coli kpsMT and rfaQPG . A possible transcriptional terminator with a hairpin loop structure found just downstream of ORF15 that is a homolog of E . coli gnd . K2 capsular polsaccharide biosynthesis in E . coli K-12 depends on cpsB (mannose-1-phosphate guanyltransferase gene), and Klebsiella cpsB, found in the downstream region of the polycistronic structure, was able to complement cpsB of E . coli . Results of transposon insertion and promoter-cloning analyses were consistent with the results of nucleotide sequence analysis.

Infect Immun, 1995 Apr, 63(4), 1329 - 35
Complement-independent binding of microorganisms to primate erythrocytes in vitro by cross-linked monoclonal antibodies via complement receptor 1; Powers JH et al.; Under certain circumstances, soluble antigens, particulate antigens, and/or microorganisms have been shown to bind to primate erythrocytes via complement receptor 1 (CR1) in the presence of specific antibodies and complement . This immune adherence reaction, specific for CR1, can lead to neutralization of antigens in the circulation and their subsequent clearance from the blood . The present experiments utilized cross-linked monoclonal antibody complexes (heteropolymers) with specificity for both CR1 and either 35S-labeled herpes simplex virus capsid or Haemophilus influenzae as prototype viral and bacterial particulate antigens, respectively . In each case, the respective specific heteropolymers facilitated binding of the target antigens (> or = 70 to 90%) in vitro to erythrocytes in the absence of complement . Several experimental protocols were employed to demonstrate that heteropolymers mediate specific, rapid (> or = 30 s), and quantitative binding of prototypical particulate pathogens to human and monkey erythrocytes but not to sheep erythrocytes, which lack CR1 . These results extend the potential use of the erythrocyte-heteropolymer system to the neutralization and clearance of particulate viral and bacterial pathogens from the blood.

Infect Immun, 1995 Apr, 63(4), 1241 - 5
Identification and purification of a conserved heme-regulated hemoglobin-binding outer membrane protein from Haemophilus ducreyi; Elkins C; A hemoglobin-binding protein (HgbA) from Haemophilus ducreyi was identified and purified . The 100-kDa HgbA was detected in all strains of H . ducreyi tested, and a somewhat larger hemoglobin-binding protein was found in one strain of Haemophilus influenzae . HgbA was purified and the amino acid sequence of the N terminus of HgbA revealed no significant homologies with known proteins . Two different antisera to HgbA from H . ducreyi 35000 recognized HgbA proteins from all tested H . ducreyi strains; they did not recognize proteins from the H . influenzae strain . Expression of HgbA was regulated by the level of heme but not by iron present in the medium . Animal species of hemoglobin competed with iodinated human hemoglobin for binding to whole cells of H . ducreyi and supported the growth of H . ducreyi . The lack of immunological cross-reactivity and the differences in hemoglobin specificities between the H . ducreyi and the H . influenzae hemoglobin-binding proteins suggest that they are unrelated.

Infect Immun, 1995 Apr, 63(4), 1201 - 10
Identification and characterization of genes encoding the human transferrin-binding proteins from Haemophilus influenzae; Gray-Owen SD et al.; Haemophilus influenzae, a strict human pathogen, acquires iron in vivo through the direct binding and removal of iron from human transferrin by an as yet uncharacterized process at the bacterial cell surface . In this study, the tbpA and tbpB genes of H . influenzae, encoding the transferrin-binding proteins Tbp1 and Tbp2, respectively, were cloned and sequenced . Alignments of the H . influenzae Tbp1 and Tbp2 protein sequences with those of related proteins from heterologous species were analyzed . On the basis of similarities between these and previously characterized proteins, Tbp1 appears to be a member of the TonB-dependent family of outer membrane proteins while Tbp2 is lipid modified by signal peptidase II . Isogenic mutants deficient in expression of Tbp1 or Tbp2 or both proteins were prepared by insertion of the Tn903 kanamycin resistance cassette into cloned sequences and reintroduction of the interrupted sequences into the wild-type chromosome . Binding assays with the mutants showed that a significant reduction in transferrin-binding ability resulted from the loss of either of the Tbps and a complete loss of binding was evident when neither protein was expressed . Loss of either Tbp2 or both proteins correlated with an inability to grow on media supplemented with transferrin-bound iron as the sole source of iron, whereas the Tbp1+ Tbp2- mutant was able to grow only at high transferrin concentrations.

Clin Infect Dis, 1995 Apr, 20 Suppl 1, S39 - 46
Recommendations for treatment of chancroid, 1993; Schulte JM et al.; Since the 1989 Sexually Transmitted Diseases Treatment Guidelines were published by the Centers for Disease Control and Prevention, changes in the efficacy of the recommended and alternative regimens for the treatment of Haemophilus ducreyi infections have been described . Among recommended agents, erythromycin remains effective, and although a single dose of ceftriaxone appears to remain effective in the United States, limited data from Kenya have shown that this regimen has been associated with treatment failures . Of alternative treatment regimens, trimethoprim-sulfamethoxazole has been associated with widespread failure, but little work has been done to further evaluate the efficacy of the amoxicillin/clavulanic acid and ciprofloxacin regimens . Of the new antimicrobials, azithromycin has been very effective in the United States, but the efficacy of this drug elsewhere has not been thoroughly evaluated . Fleroxacin has been very effective in Kenya . Data from Africa indicate that patients who are infected with the human immunodeficiency virus do not respond to therapy as well as patients who are not, and patients who are uncircumcised may not respond as well to therapy as do patients who are circumcised.

Clin Infect Dis, 1995 Apr, 20 Suppl 1, S3 - 22
Early intervention for persons infected with human immunodeficiency virus; Branson BM; Early intervention for persons infected with human immunodeficiency virus (HIV) involves characterization of the stage of HIV disease, institution of therapy to prevent associated infections and postpone deterioration of immune function, and assistance in preventing transmission of the virus . This review examines the available data on the efficacy of current recommendations regarding the evaluation and management of persons with early HIV infection . Existing evidence supports the efficacy of physical examination, monitoring of the CD4+ cell count, tuberculin testing (with chemotherapy for persons who test positive), anergy testing, Papanicolaou testing and screening for gonorrhea and chlamydial infection (for high-risk women), screening for syphilis, antiretroviral therapy (for symptomatic patients), and guidance in reducing the transmission of HIV . Recommended measures for which evidence of clinical efficacy is less certain include immunization against infections due to influenza virus, Streptococcus pneumoniae, Haemophilus influenzae, and hepatitis B virus as well as antiretroviral therapy for asymptomatic persons . Quantitative measurement of viral titers appears promising for the monitoring of HIV disease and antiretroviral therapy; the correlations of these titers with clinical end points need to be confirmed.

Clin Infect Dis, 1995 Apr, 20(4), 924 - 30
Failure of treatment for chancroid in Rwanda is not related to human immunodeficiency virus infection: in vitro resistance of Haemophilus ducreyi to trimethoprim-sulfamethoxazole; Bogaerts J et al.; A comparative open study was performed to evaluate the efficacy of single doses of ciprofloxacin (500 mg) and trimethoprim-sulfamethoxazole (TMP-SMZ; 640 mg/3,200 mg) for the treatment of culture-proven chancroid . Clinical cure or improvement was observed 7 days after treatment in 32 (76.2%) of the 42 patients who received ciprofloxacin and 21 (52.5%) of the 40 patients who received TMP-SMZ (P = .04) . Cultures for one (4.5%) of 22 patients not cured with ciprofloxacin and 16 (59.3%) of 27 patients not cured with TMP-SMZ were still positive for Haemophilus ducreyi 7 days after treatment (P < .001) . Although 77 (71.3%) of the 108 patients tested were seropositive for HIV-1 antibody, HIV infection and the degree of CD4+ lymphocyte depletion had no effect on clinical and bacteriologic outcome . All isolates of H . ducreyi were highly susceptible to ciprofloxacin (MIC, 0.004-0.06 mg/L) . In contrast, resistance to TMP-SMZ (MIC, > or = 4/76 micrograms/mL) was observed in 48.9% of isolates (22 of 45) and was significantly associated with treatment failure . Therefore, the administration of TMP-SMZ, in single or multiple doses, is no longer indicated for the treatment of chancroid in Rwanda.

Clin Infect Dis, 1995 Apr, 20(4), 854 - 60
Etiology of acute respiratory tract infections among children in a combined community and hospital study in Rio de Janeiro; Sutmoller F et al.; We reviewed data collected between January 1987 and December 1989 on the etiology of acute respiratory infections (ARI) among 827 children in two low-income communities and a hospital in Rio de Janeiro . Respiratory syncytial virus was identified in 38% of cases of ARI, influenza A virus in 1%, parainfluenza 3 virus in 1%, and multiple viruses in 1% . Respiratory syncytial virus was most prevalent among hospitalized children, with seasonal increases in the late fall and winter . The principal bacterial pathogens were Staphylococcus aureus, gram-negative bacteria, Streptococcus pneumoniae, and alpha-hemolytic streptococci . Specimens that were most often positive were pleural fluid (46%) and specimens from other normally sterile sites (24%); normally sterile sites included the CSF, trachea, and lungs . Urine counterimmunoelectrophoresis for S . pneumoniae and Haemophilus influenzae polysaccharide antigens was positive in 3% and 2% of cases, respectively . Pharyngeal cultures yielded low numbers of S . pneumoniae and H . influenzae organisms and higher numbers of gram-negative bacteria . This study demonstrates the high incidence of ARI (4.5 cases per 100 child-weeks) among children in Rio de Janeiro and the high morbidity associated with the illness (ARI is responsible for 25%-50% of all pediatric hospitalizations) and the fact that continued attention must be paid to both viral and bacterial agents of ARI.

J Paediatr Child Health, 1995 Apr, 31(2), 99 - 104
Clinical manifestations and outcome of Haemophilus influenzae type b disease; Gilbert GL et al.; OBJECTIVE: To document clinical manifestations, laboratory findings and outcome of childhood Haemophilus influenzae type b (Hib) infections . METHODOLOGY: Medical records of 235 children with Hib disease admitted to hospital during a 2 year period were reviewed; additional information was obtained by questionnaire and follow up 6 weeks after discharge . RESULTS: Three-quarters of patients presented with either meningitis or epiglottitis . Children with epiglottitis were older, had shorter illnesses and were less likely to have had antibiotics before admission than those with meningitis; 38% of the latter had been given some antibiotic therapy, with no apparent effect on the outcome . Fever persisted for 7 days or more in 23% of patients with meningitis . Death from meningitis occurred in 3.8% of patients and was due to fulminating disease . CONCLUSIONS: These data will assist in recognition and appropriate management of Hib disease as the clinical manifestations become less familiar following the introduction of immunization . Specific laboratory diagnosis is required for accurate surveillance, which should be maintained in order to ensure high immunization rates.

Pediatr Infect Dis J, 1995 Apr, 14(4 Suppl), S23 - 6
Otitis media complications and treatment failures: implications of pneumococcal resistance; Poole MD; Classic complications of untreated otitis media include meningitis, lateral sinus thrombosis and chronic suppurative otitis media . In the past, in countries where otitis media is usually treated, complications have been rare, because of the good activity of almost all orally administered antibiotics against the most common cause of complications, Streptococcus pneumoniae . Treatment failures were usually caused by beta-lactamase-producing nontypable Haemophilus influenzae or by Moraxella (Branhamella) catarrhalis and were rarely associated with serious systemic infections . With the advent of multidrug-resistant pneumococci, however, serious and fatal infections can occur in the face of our most potent antimicrobial agents . The consequences of the emergence of multidrug-resistant pneumococci are likely to include more persistent purulent otitis media, increased usage of broad-spectrum antibiotics, an increase in surgical treatment rates for otitis media and, eventually, an increase in suppurative complications of otitis media . Medical treatment failures probably already surpass eustachian tube dysfunction as the most common reason for tympanostomy tube insertion . Multidrug-resistant pneumococci may be expected to change the way in which primary and secondary care is currently administered.

Pediatr Infect Dis J, 1995 Apr, 14(4 Suppl), S19 - 22
Multicenter trial of cefpodoxime proxetil vs . amoxicillin-clavulanate in acute lower respiratory tract infections in childhood . International Study Group; Klein M; Acute lower respiratory tract infections in children are a worldwide public health problem, with an estimated 4 million potentially preventable deaths every year . Until recently, penicillin and related drugs were the treatment of choice for empiric therapy of paediatric lower respiratory tract infections . However, concerns over the emergence of penicillin-resistant strains of Streptococcus pneumoniae and beta-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis have led physicians to turn increasingly towards alternatives, such as the third generation cephalosporins . The oral extended spectrum cephalosporin cefpodoxime proxetil is highly active against the bacterial pathogens commonly associated with childhood lower respiratory tract infections . In order to evaluate its clinical efficacy in children with acute febrile lower respiratory tract infections, an international, multicenter, comparative, randomized open study was conducted in children ages 3 months to 11.5 years . Of 348 cases enrolled, 234 were randomized to cefpodoxime proxetil (8 mg/kg/day twice daily) and 114 to amoxicilin/clavanulate (amoxicillin 40 mg/kg/day 3 times a day) . The duration of treatment was 10 days . Pretreatment diagnosis was pneumonia in 292 patients, bronchiolitis in 19 patients and acute bronchitis in 37 patients . Pathogens isolated from 59 cases included H . influenzae (47.5%), S . pneumoniae (23.7%), M . catarrhalis (11.9%) and Haemophilus parainfluenzae (6.8%) . Clinical efficacy was evaluable in 278 children at the end of treatment when 95.2% of patients in the cefpodoxime proxetil group and 96.7% of patients in the amoxicillin/clavanulate group showed a satisfactory clinical response (cured or improved) . The improvement was sustained at the follow-up visit, 10 to 20 days after completion of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Pediatr Infect Dis J, 1995 Apr, 14(4 Suppl), S12 - 8
Clinical experience with cefpodoxime proxetil in acute otitis media; Cohen R; Although it varies from country to country, there is a worrying worldwide increase in antibiotic resistance among pathogens causing otitis . This has led to a search for therapeutic alternatives to the reference treatment, which is still amoxicillin in many countries . Cefpodoxime proxetil is one such alternative . Six comparative randomized trials of cefpodoxime proxetil in childhood acute otitis media have been published or presented at international conferences . They involved a total of 1188 patients, 658 of whom received cefpodoxime proxetil and 530 of whom received the comparator drug (amoxicillin/clavulanic acid in 3 trials, cefaclor in 1, and cefixime in 2); duration of treatment varied from 5 days for cefpodoxime proxetil to 10 days for amoxicillin/clavulanic acid, and the age of the children included ranged from 2 months to 12 years . The clinical efficacy of cefpodoxime proxetil was at least equivalent to that of the comparators in 4 trials and significantly better in 2 trials . Firstly, in one study vs . amoxicillin/clavulanic acid, the superiority of cefpodoxime proxetil (8 mg/kg/day twice daily) in terms of healing at the end of treatment and in terms of the number of normal tympanograms at the follow-up visit was shown . Secondly, in a study performed by our group, vs . cefixime, cefpodoxime proxetil (8 mg/kg/day twice daily) showed a better healing rate at the end of treatment in febrile and painful acute otitis media . The microbiologic and pharmacokinetic data show that cefpodoxime proxetil is one of the most active compounds against Haemophilus influenzae and Streptococcus pneumoniae.(ABSTRACT TRUNCATED AT 250 WORDS)

J Clin Microbiol, 1995 Apr, 33(4), 1036 - 8
Alterations in sample preparation increase sensitivity of PCR assay for diagnosis of chancroid; Johnson SR et al.; A PCR assay for the detection of Haemophilus ducreyi in clinical specimens taken from genital ulcers was developed . Although H . ducreyi, when present in such specimens, could be detected by PCR, the sensitivity of the assay was reduced by the presence of Taq polymerase inhibitors in the specimen . The sensitivity of the PCR assay was improved by the use of detergents in preparing nuclei acids from clinical specimens and by the inclusion of a dialysis step prior to amplification . In addition, sodium phosphate included in the transport medium was found to be an inhibitor of the Taq polymerase.

Antimicrob Agents Chemother, 1995 Apr, 39(4), 910 - 6
Antimicrobial activity of SM-17466, a novel carbapenem antibiotic with potent activity against methicillin-resistant Staphylococcus aureus; Sumita Y et al.; The in vitro and in vivo antibacterial activities of SM-17466, a new 1 beta-methyl carbapenem, were evaluated against a wide range of clinical bacterial isoaltes and compared with the activities of meropenem, imipenem, vancomycin, and arbekacin . SM-17466 had a broad spectrum of action against gram-positive bacteria, showing especially potent activity against methicillin-resistant staphylococci . The MICs of SM-17466, meropenem, imipenem, vancomycin, and arbekacin at which 90% of clinical isolates of methicillin-resistant Staphylococcus aureus were inhibited were 3.13, 50, 100, 1.56, and 3.13 micrograms/ml, respectively . This activity of SM-17466 was almost equivalent to those of the antibiotics used for the treatment of infections caused by this organism . SM-17466 also showed bactericidal activity against methicillin-resistant S . aureus . In contrast, SM-17466 was less active against gram-negative bacteria, especially against Pseudomonas aeruginosa, compared with the other carbapenems; however, of the carbapenems, SM-17466 exhibited the highest activity against Haemophilus influenzae and Bacteriodes fragilis . SM-17466, at a 50% inhibitory concentration of less than 1 microgram/ml, bound to penicillin-binding proteins 1 to 4 in methicillin-susceptible S . aureus and also had good binding to penicillin-binding protein 2' in a methicillin-resistant strain (50% inhibitory concentration, 5.9 micrograms/ml) . This high affinity, which was 10 and 20 times greater than those for meropenem and imipenem, respectively, was reflected in the potent activity of SM-17466 against methicillin-resistant S . aureus . SM-17466 demonstrated excellent in vivo efficacy against methicillin-susceptible and -resistant S . aureus strains in a mouse peritoneal infection model: the efficacy of SM-17466 against methicillin-resistant strains was equal to or one-third that of vancomycin . This activity was comparable to the in vitro activity of SM-17466 . The subcutaneous injection of SM-17466 in mice revealed that the half-life of SM-17466 in serum was about 18 min, intermediate between those of vancomycin and arbekacin and 1.5-fold that of imipenem-cilastatin . SM-17466 was resistant to hydrolysis by swine renal dehydropeptidase I, to an extent comparable to the resistance shown by meropenem.

Nippon Jibiinkoka Gakkai Kaiho, 1995 Apr, 98(4), 659 - 68
{The effect of cefaclor and cefixime on nasopharyngeal pathogens in children}; Tomiyama M; Changes in nasopharyngeal flora were investigated in children with acute otitis media and with acute exacerbations of chronic sinusitis in whom antibiotic therapy of relatively long duration was required until substantial improvement in clinical findings was achieved . 1 . The antibiotics used were two cephalosporins, i.e., cefaclor (CCL) and cefixime (CFIX), administered to 18 patients each for 1 week and to 26 and 20 patients, respectively, for 2 weeks . Bacteriologic examination of the nasopharyngeal mucosa was performed at the first visit and at 1 week in those who underwent antibiotic therapy for 1 week, and at the first visit and at 1 and 2 weeks in those treated with antibiotics for 2 weeks . 2 . The elimination rates for the infecting microorganisms in the patients in the CCL-treated group were 30% for Haemophilus influenzae, 83% for Staphylococcus aureus, 100% for Streptococcus pyogenes and 100% for Streptococcus pneumoniae at 1 week, and 18% for H . influenzae, 100% for S . aureus and 100% for S . pyogenes at 2 weeks of antibiotic therapy . Replacement of S . aureus and S . pyogenes by H . influenzae was observed . 3 . The elimination rates for infecting bacteria in the patients in the CFIX-treated groups were 61% for H . influenzae, 50% for S . aureus, 75% for S . pyogenes, 80% for S . pneumoniae and 100% for Moraxella catarrhalis at 1 week, and 72% for H . influenzae, 0% for S . aureus, 100% for S . pyogenes, and 0% for S . pneumoniae at 2 weeks of antibiotic therapy . The elimination rate for H . influenzae at 2 weeks was significantly higher than the corresponding value for the CCL-treated group . Replacement of H . influenzae by S . aureus and S . pneumoniae and of S . pyogenes by S . aureus was detected . 4 . There was one patient with acute otitis media in the CFIX-treated group in whom a clinical relapse occurred due to H . influenzae persisters in the nasopharynx . Thus the diagnosis in this patient was so-called "recurrent otitis media" . 5 . H . influenzae tended to persist after exposure to therapeutically adequate concentrations of CCL, as did S . aureus and S . pneumoniae following treatment with CFIX . Thus, it would seem that ample heed must be given to persistence, particularly of H . influenzae and S . pneumoniae, the most common causative agents of acute otitis media in childhood . 6 . A significant rise in the MICs of the cephalosporins was observed in 4 of 43 patients in whom the same type of organism was isolated from the nasopharynx at weekly intervals during antibiotic therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Pediatrics, 1995 Apr, 95(4), 522 - 7
Safety and immunogenicity of PRP-T combined with DTP: excretion of capsular polysaccharide and antibody response in the immediate post-vaccination period; Miller MA et al.; OBJECTIVE . To evaluate whether combining Haemophilus influenzae type b capsular polysaccharide covalently linked to tetanus toxoid (PRP-T) and diphtheria-tetanus-pertussis (DTP) in one syringe produced a vaccine that was safe and immunogenic . DESIGN . Randomized clinical trial . SETTING . Suburban New Orleans pediatric population . PARTICIPANTS . Convenience sample of 150 healthy infants . METHODS . Enrollees were randomized to receive DTP and PRP-T in one injection (Group 1), DTP and PRP-T separately (Group 2), or DTP and H influenzae type b capsular saccharide coupled to a nontoxic variant of diphtheria toxin, CRM197 (HbOC) separately (Group 3) at 2, 4, and 6 months of age . All infants received oral polio vaccine at 2 and 4 months of age . Parents were instructed to record side effects on a standardized form after each vaccine administration . Blood was drawn before each immunization and at 7 months of age; an additional blood and a urine specimen was obtained 2 to 3 days after one of the vaccination visits . Serum was assayed for H influenzae anticapsular antibody (anti-PRP), anti-pertussis toxoid, anti-fimbrial hemagglutinins, anti-diphtheria and anti-tetanus toxoid antibodies, and antibody to polio viruses . Urine was assayed for H influenzae type b capsular polysaccharide . RESULTS . The rate of occurrence of fever did not differ significantly between groups . Local swelling and erythema occurred more often at the administration site in Group 1 infants than at the DTP administration sites of infants in Groups 2 and 3 after the first and second vaccinations . The mean concentration of all antibodies we assayed did not differ significantly when Group 1 and 2 infants were compared . HbOC recipients (Group 3) had lower mean anti-H influenzae anticapsular antibody and higher mean anti-diphtheria and anti-tetanus antibody concentrations after two and three doses compared with Group 1 and Group 2 infants . No group had a significant change in mean anti-PRP antibody concentration 2 to 3 days after vaccination with any dose . After vaccination, antigenuria occurred less frequently in Group 1 infants (54%, 78%, and 72% in Groups 1, 2, and 3, respectively, P < .01) . CONCLUSIONS . Combining PRP-T and DTP produced a combination vaccine associated with a slight increase in the rate of erythema and swelling but with similar immunogenicity of the vaccine components and oral polio vaccine.

Clin Exp Immunol, 1995 Apr, 100(1), 47 - 53
Severity of infections in IgA deficiency: correlation with decreased serum antibodies to pneumococcal polysaccharides and decreased serum IgG2 and/or IgG4; French MA et al.; In order to define abnormalities of humoral immunity which determine susceptibility to respiratory tract infections in IgA-deficient adults, serum IgG subclass concentrations, and serum concentrations of pneumococcal antibodies and Haemophilus influenzae type B (Hib) antibodies sera from IgA-deficient adults with and without susceptibility to respiratory tract infections were compared . Infection susceptibility was not related to the degree of IgA deficiency, but was related to deficiency of IgG4 and, to a lesser extent, IgG2, as well as to low basal serum concentrations of pneumococcal polysaccharide antibodies . The combination of IgG2 and/or IgG4 deficiency and a non-protective basal serum concentration of antibody against two or more pneumococcal polysaccharides was present in the serum of six of 12 (50%) patients with severe infections, but only one of 44 (2%) patients without infections . Furthermore, the preservation of antibody responses against the most immunogenic pneumococcal polysaccharide type 3, but not against the less immunogenic types 7F, 9N and 14, in patients with severe infections suggested that abnormalities of pneumococcal polysaccharide antibody responses might include defects of affinity maturation.

Avian Dis, 1995 Apr-Jun, 39(2), 304 - 8
Phenotypic and molecular characterization of V-factor (NAD)-independent haemophilus paragallinarum; Miflin JK et al.; In South Africa from early 1989 onward, strains of Haemophilus paragallinarum not requiring nicotinamide adenine dinucleotide (NAD) have been isolated from commercial chickens suffering from infectious coryza . Fifteen of these field isolates were characterized by biochemical typing, serotyping, restriction endonuclease analysis (REA), and ribotyping . The chosen isolates represented diversity in geographic location, time of disease outbreak, and type of flock . All were typical of the species in biochemical properties, except that they were NAD-independent, and all were Page serovar A . REA was performed with three enzymes: HindIII, HpaII, and SspI . All isolates gave identical REA profiles with all three enzymes . Ribotyping was performed using a probe that consisted of the plasmid pUC19 into which the 16S rRNA operon of H . paragallinarum had been inserted . All 15 isolates gave the same ribotyping profile using each of the three enzymes . As a group, the NAD-independent strains gave REA profiles and ribotypes that were very different from a range of classic South African strains isolated before 1989 . Our results strongly suggest that the NAD-independent isolates are clonal in nature.

J Chemother, 1995 Apr, 7(2), 97 - 9
Aminoglycoside resistance in Haemophilus influenzae; Gomez-Lus R et al.; From September 1, 1990 to December 31, 1993 a total of 425 Haemophilus influenzae strains from clinical specimens were isolated in the Microbiology Laboratory of the Zaragoza University Hospital . Of these strains, 16 (33.33%) were resistant to kanamycin, neomycin, paromomycin, lividomycin and streptomycin . Demonstration of APH (3')-I activity by the phosphocellulose paper binding assay, based on the incorporation of radiolabel into lividomycin was sixfold greater than into butirosin . Two DNA probes were prepared to screen for the genes encoding APH(3') activity in kanamycin-resistant H . influenzae . Homology was observed between the aphA1 DNA probe and total cellular DNA from all 16 APH(3')-I producers . On the other hand, streptomycin-resistance was not through metabolic modification of the antibiotic.

J Chemother, 1995 Apr, 7(2), 140 - 5
Comparative activities of pefloxacin and ciprofloxacin in the treatment of chronic respiratory tract infections; Scaglione F et al.; To determine the efficacy in vivo of pefloxacin and ciprofloxacin in the treatment of acute infectious bronchopneumopathies, 90 patients, suffering from acute exacerbation of chronic bronchitis and with no known allergies to quinolones, were admitted to the study . Patients were randomly divided into three groups of 30; the first group was dosed with pefloxacin 800 mg i.v . every 24 hours; the second group with pefloxacin 800 mg per os every 24 hours and the third with 500 mg per os of ciprofloxacin every 12 hours . Blood and bronchial secretion samples were simultaneously collected 2, 4, 8, 12, 14 and 24 hours after the first daily dose of antibiotic . Serum and bronchial secretion concentrations of pefloxacin and ciprofloxacin were determined by using a microbiological agar disk diffusion assay, employing Escherichia coli Kp 712 as test organism . Eradication of responsible microorganisms (Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis) were achieved in 98% of patients around 72 hours post treatment . Generally, both antibiotics expressed similar bactericidal properties when orally administered, while intravenous administration of pefloxacin displays a more rapid antibacterial action in comparison with the oral administration schedules . Maximal concentrations of both drugs in bronchial secretion were recorded at the same time after treatment (4 hours), with concentrations of about 2.5 micrograms/ml . Pefloxacin, having a longer half-life, was found 24 hours post-treatment with plasma concentrations of 1.5 micrograms/ml following a single oral dose of 800 mg . Ciprofloxacin, having a shorter half-life, showed a peak of about 1 microgram/ml, 12 hours after administration (500 mg/12 hours/os).

J Antimicrob Chemother, 1995 Apr, 35(4), 535 - 9
Evaluation of the in-vitro activity of furopenem (SY5555 or SUN5555) against respiratory tract pathogens and beta-lactamase producing bacteria; Cormican MG et al.; Furopenem is a novel orally active penem . In this study, furopenem was highly active in vitro against Streptococcus pneumoniae (MIC90 0.03 mg/L), Haemophilus influenzae (MIC90, 2 mg/L), and Moraxella catarrhalls (MIC90, 0.5 mg/L) . Its activity was not reduced by a variety of beta-lactamase enzymes, however beta -lactam resistance by other mechanisms was associated with higher MICs.

Pediatr Infect Dis J, 1995 Apr, 14(4), 286 - 94
Anti-capsular polysaccharide antibody concentrations in saliva after immunization with Haemophilus influenzae type b conjugate vaccines; Kauppi M et al.; IgG and IgA antibodies to Haemophilus influenzae type b (Hib) capsular polysaccharide (PS) were measured in saliva of 7- to 19-month-old children after vaccination with 2 or 3 doses of Hib conjugate vaccine . Both the concentration and the prevalence of these antibodies were higher after 3 than after 2 doses of vaccine . The presence and concentration of IgG Hib PS antibodies in saliva correlated with their concentration in serum . Fifty-four percent (20 of 37) of the children with serum IgG concentrations higher than 30 micrograms/ml had detectable salivary IgG, whereas the 21 children with a low serum IgG concentration (< 3 micrograms/ml) had no IgG in saliva . The IgA anti-Hib PS in saliva was mainly secretory and was found in saliva of 29% (19 of 65) of the children who had no detectable serum IgA anti-Hib PS . The results suggest that the IgG anti-Hib PS in saliva was derived from serum, whereas the IgA antibodies were locally produced . The Hib PS antibodies on mucosa are suggested to be responsible for the reduction of Hib carriage observed among children vaccinated with Haemophilus type b conjugates.

J Otolaryngol, 1995 Apr, 24(2), 92 - 7
Acute epiglottitis in children: results of a large-scale anti-Haemophilus type B immunization program; Wurtele P; The incidence of acute epiglottitis in children is declining in the province of Quebec, Canada . In 1988, a PRP-D anti-Haemophilus type B vaccine was introduced into the routine vaccination schedule of 18-month-old children . A substantial reduction in the occurrence of acute epiglottitis was perceived by clinicians . Since 1992, improved new vaccines (PRP-T, HbOC, PRP-OMPC), given to 2-month-old infants, have been expected to increase the efficacy of the immunization program . The impact of the immunization program on preventing acute epiglottitis was verified using a provincial database system called Med-Echo . In the presumably vaccinated target population (0 to 6 years old), 15 children suffered acute epiglottitis in 1993, whereas 97 cases were reported on the average for each yearly period from 1984 to 1987, just before the program's inception . Thus, the incidence of acute epiglottitis in preschoolers was reduced to 15.4% of its former level . The overall efficacy of the immunization program in preventing acute epiglottitis, therefore, is estimated to be 84.6%.

Pathol Biol (Paris), 1995 Apr, 43(4), 324 - 8
{Detection of beta-lactamase in samples obtained after tonsillectomy in children}; Borderon JC et al.; Production of beta-lactamase was detected using a microbiological assay (Guts test) in samples of tonsils, and by in Haemophilus growing from the same samples of both tonsils obtained from 30 children aged 2 to 13 years (18 aged < 6 years and 12 aged > or = 6 years) . Two pieces from each tonsil, core and superficial, were studied . The procedure included direct microscopic examination of smears, and culture to identify Haemophilus, beta-haemolytic streptococci and Streptococcus pneumoniae . Guts test was positive in tonsillar tissue obtained from 26 children (14 aged < 6 years and 2 aged > or = 6 years) (p < 0.01) . In 10 of them (9 aged < 6 years and 1 aged > or = 6 years) (p < 0.05) grew beta-lactamase producer Haemophilus influenzae . One to three varieties of Haemophilus could be found in 28 children (11 with H . influenzae = 5 beta-lactamase +, 8 with Haemophilus parainfluenzae = 3 beta-lactamase +); Group A, C, or G streptococci in 5 children, but no strain of Streptococcus pneumoniae . No difference could be demonstrated between core and superficial samples: beta-lactamase activity was positive in superficial samples from 26 children and core samples from 24 . Almost all bacteria described grew from superficial as well as (slightly but no significantly less) from core samples.

Diagn Microbiol Infect Dis, 1995 Apr, 21(4), 223 - 5
A survey of beta-lactamase-producing Haemophilus influenzae . An evaluation of 5750 isolates; Rittenhouse SF et al.; Previous studies have reported that 15%-34% of Haemophilus influenzae produce beta-lactamase . A surveillance program was developed by SmithKline Beecham Clinical Laboratories to determine the current percentage of beta-lactamase-producing H . influenzae from five selected geographic locations in the United States . In 1993, results of 5750 isolates from specimens submitted to five reference clinical laboratories were evaluated . Data were collected from 29 states and the District of Columbia . The percentages of beta-lactamase-producing H . influenzae was 33% and ranged from 22%-40% for the individual states.

Aust Vet J, 1995 Apr, 72(4), 135 - 8
Characterisation of Pasteurella multocida isolated from fowl cholera outbreaks on turkey farms; Blackall PJ et al.; Biochemical profiles, restriction endonuclease analysis (REA) and ribotyping were used to investigate Pasteurella multocida isolates from outbreaks of fowl cholera on 7 turkey farms in New South Wales . While only a single isolate was available from 5 of the farms, multiple isolates, 4 and 12 respectively, were available from the other 2 farms . The available field evidence suggested that 8 outbreaks had occurred with one farm suffering 2 outbreaks . The isolates obtained were all confirmed as Pasteurella multocida . Biochemical profiles allocated the isolates to 4 groups, 3 being variants of P multocida subsp multocida and the fourth being P multocida subsp septica . REA performed with HpaII established 7 groups . Ribotyping using the HpaII digests probed with the 16S rRNA operon of Haemophilus paragallinarum recognised the same 7 groups as REA . Unlike the biochemical profiles, both REA and ribotyping provided a fine subdivision that identified outbreaks as either related or unrelated . The REA and ribotyping patterns as well as biochemical profiles were stable for all isolates from the outbreaks in which multiple isolates were obtained from either the same bird or from different birds . REA and ribotyping were found to be superior to biotyping methods for the investigation of fowl cholera outbreaks.

J Clin Microbiol, 1995 Apr, 33(4), 787 - 90
Simplified PCR for detection of Haemophilus ducreyi and diagnosis of chancroid; West B et al.; A simplified PCR was developed for detection of Haemophilus ducreyi in samples from chancroid patients . The strategy included a straightforward chloroform extraction sample preparation method, a one-tube nested PCR to minimize contamination risks, and a colorimetric method for detection of products . Primers were designed from published nucleotide sequences of the 16S rRNA gene of H . ducreyi, with longer outer primers for annealing at a higher temperature and shorter inner primers labelled with biotin and digoxigenin for binding with avidin and colorimetric detection . The PCR technique detected all 35 strains of H . ducreyi tested, from four different geographical regions, and was negative for other, related strains of bacteria and for the common contaminating bacteria tested . Of 25 samples from H . ducreyi culture-positive chancroid patients, 24 were PCR positive and 1 produced a weak reaction . Of 83 samples from clinical cases of chancroid in the Republic of South Africa, 69 were PCR positive . The sensitivity of PCR compared with that of clinical diagnosis was 83% . All 50 negative control samples were negative . Encouraging results were also obtained with a consecutive series of 25 genital ulcer patients in Tanzania, of whom 9 were PCR positive . The adaptations of this simplified PCR strategy, at the sensitivity and specificity levels obtained, mean it will be useful for detection of H . ducreyi in areas where the organism is endemic, particularly where testing by culture is difficult or impossible.

Vaccine, 1995 Apr, 13(6), 525 - 31
Development of a guinea pig model to assess immunogenicity of Haemophilus influenzae type b capsular polysaccharide conjugate vaccines; Siber GR et al.; There is currently no animal model which reliably predicts the immunogenicity of Haemophilus influenzae type b (Hib) polysaccharide-protein conjugate vaccines in human infants . We evaluated various Hib vaccines in guinea pigs using techniques similar to the United States potency test for adsorbed diphtheria and tetanus toxoids with a view to developing a method for evaluating the potency of a combined adsorbed tetanus, diphtheria, pertussis and Hib conjugate vaccine . Groups of 6-8 guinea pigs received 1.5 single human doses of vaccine at 0 and at 6 or 8 weeks and were bled at 6 weeks and 2 weeks after the booster injection . Total antibodies to polyribosylribitolphosphate (PRP), the Hib capsular polysaccharide, were measured in individual animals and in serum pools by radioimmunoassay . The relative antibody responses of guinea pigs to Hib conjugate vaccines qualitatively resembled those of human infants . Unconjugated polysaccharide was not immunogenic; PRP-D produced a low antibody response, HbOC, PRP-T (Merieux) and Hib-T (MPMBL) produced a low response to the first dose and a strong anamnestic response to the booster (geometric mean anti PRP > 1 micrograms ml-1) . PRP-OMP uniquely produced a strong response after the first dose which was further boosted by the second dose . Experimental Hib-T vaccine lots with low levels of conjugation were poorly immunogenic in guinea pigs . Combinations of DTP and Hib-T vaccines showed equivalent or greater immunogenicity than Hib-T alone . We propose that the guinea pig model may be useful to verify the immunogenicity of PRP conjugate vaccines and for pre-clinical evaluations of DTP-Hib combination vaccines containing PRP conjugates.

MMWR Morb Mortal Wkly Rep, 1995 Mar 31, 44(12), 244 - 7
Vaccination coverage surveys in county health departments--Kansas, 1993-1994.
{Pasteurelloses}
Avril JL, Donnio PY.

According to the genetic relationships among Gram-negative bacilli the genus Pasteurella is included with the genus Haemophilus and the genus Acinobacillus within the family Pasteurellacae . Pasteurella multocida, the type species, is responsible for the majority of human Pasteurella infections . P . multocida is a member of the normal flora in the upper respiratory tract of many mammals or birds . It causes sporadic or epidemic diseases among different animal species, particularly pneumonia and atrophic rhinitis in swine in intensive breeding stations . The most common human infection with P . multocida is a local cellulitis following dog or cat bites and scratches . Serious local complications are sometimes responsible for prolonged disability . The respiratory tract is the second human source of P . multocida isolates . The frequency of recovery of P . multocida from oropharynx of apparently healthy pig breeders suggests that respiratory pasteurellosis could be an occupational disease . The mechanisms of virulence of P . multocida are unclear . Several factors are involved: capsules preventing phagocytosis, a dermonecrotic toxin causing experimental atrophic rhinitis, hyaluronidase, neuraminidase and proteases . Penicillin is considered to be the drug of choice for Pasteurella infection . Tetracyclin is efficient for bites but has no bactericidal effect . Oxacillin, first-generation cephalosporins, macrolides and aminoglycosides have poor activities . In the case of beta-lactamase producing strains a bactericidal effect could be achieved with fluoroquinolones or third generation cephalosporins.

Med J Aust, 1995 Mar 6, 162(5), 245 - 8
The impact of vaccination against invasive Haemophilus influenzae type b disease in the Sydney region; McIntyre PB et al.; OBJECTIVE: To evaluate the incidence of invasive Haemophilus influenzae type b (Hib) disease relative to rates of Hib vaccination in a well defined population . DESIGN AND SUBJECTS: Cases of invasive Hib disease were identified by active laboratory surveillance for the period 1989-1994, and retrospectively for 1985-1987 . Vaccination rates were determined by telephone interview of families with children aged 0-4 years, identified in a random telephone directory sample of 4000 households . The receipt and time of vaccination were validated from general practitioner records for a 50% subsample of children . SETTING: Sydney Statistical Division, with a population of 263,758 children aged 0-4 years in 1990 . RESULTS: Hib vaccination rates were relatively low before the introduction of government-funded vaccination programs in May 1993, especially for children under 18 months for whom multiple doses are required . Rates rose from fewer than 9% (95% CI, 4%-13%) in May 1993 to 48% (CI, 40%-56%) in August 1993 for children under 18 months, and from 31% (CI, 26%-36%) to 45% (CI, 40%-51%) for children aged 19-60 months . The age-specific incidence of Hib disease was inversely related to the vaccination rate . Forecasting of Hib disease incidence by the Box-Jenkins method showed that from September 1993, when about a 50% vaccine uptake was achieved in the eligible age group, overall incidence was substantially lower than expected . CONCLUSIONS: These data provide good evidence that the decrease in Hib disease incidence in 1993-1994 is an effect of vaccination, and not annual or seasonal variation . The impact of Hib vaccination appears to have been greater than would be expected from protection of vaccinated children alone . Invasive Hib disease is likely soon to become a rare cause of serious childhood infection in Australia.

MMWR Morb Mortal Wkly Rep, 1995 Mar 3, 44(8), 142 - 3, 149-50
Vaccination coverage of 2-year-old children--United States, January-March, 1994; The changing epidemiology of invasive bacterial infections in Massachusetts children et al.; Massachusetts Public Health Biologic Laboratories, BostonCoincident with the licensure of Haemophilus influenzae b conjugate vaccines from 1987 to 1990, the incidence of meningitis and other invasive infections caused by H influenzae type b declined in Massachusetts children by 87% and 91%, respectively . By 1991, Neisseria meningitidis had replaced H influenzae b as the leading cause of bacterial meningitis, accounting for 57% of cases . During the period 1984 through 1991, serogroup C displaced sero-group B as the most common cause of N meningitidis disease . Streptococcus pneumoniae caused 92% of nonmeningitis invasive disease, with sero-groups 14, 6, 19, 18, 4, 23, and 9 causing 94.5% of infections . These findings have implications for the development of additional polysaccharide-protein conjugate vaccines for the prevention of childhood infections.

J Infect Dis, 1995 Mar, 171(3), 713 - 7
Phase-variable expression of the 145-kDa surface protein of Brazilian purpuric fever case-clone strains of Haemophilus influenzae biogroup aegyptius; Rubin LG; Clonally related strains of Haemophilus influenzae biogroup aegyptius have recently been associated with Brazilian purpuric fever (BPF) . Antibodies to a 145-kDa minor outer membrane protein (P145) are bactericidal and protect against experimental bacteremia . To determine if P145 is conserved among case-clone strains, case-clone strains were screened for P145 expression . Assays of a large number of colonies of each strain using colony immunoblot revealed colonies reactive with anti-P145 sera in all 17 case-clone strains . P145 was expressed at a low frequency (0.08%-2.2% of colonies) in 14 strains and at a high frequency (> 98%) in 3 strains . Expression of P145 by reactive colonies was confirmed by SDS-PAGE . Also, anti-P145-nonreactive variant colonies of P145-expressing strains were detected in 0.4%-1.5% of colonies . These findings indicate P145 is conserved among BPF case-clone strains and is subject to phase-variable expression.

Otolaryngol Head Neck Surg, 1995 Mar, 112(3), 375 - 82
Head and neck space infections in infants and children; Ungkanont K et al.; A retrospective study was performed in 117 children with head and neck space infections treated at the Children's Hospital of Pittsburgh from January 1986 through June 1992 . Peritonsillar space infections were the most common (49%), followed by retropharyngeal (22%), submandibular (14%), buccal (11%), parapharyngeal (2%), and canine (2%) space infections . The most common pathogens isolated (N = 78) were the aerobes beta-hemolytic streptococcus (18%) and Staphylococcus aureus (18%), the anaerobes Bacteroides melaninogenicus (17%) and Veillonella (14%), and the gram-negative organism Haemophilus parainfluenzae (14%) . beta-Lactamase production by aerobic pathogens was detected in 22% of cultures . Computed tomography scans (N = 16) were reviewed in blinded fashion and compared with operative findings . The sensitivity of computed tomography scan in detecting the presence of an abscess vs . cellulitis was high (91%), whereas the specificity was rather low (60%) . Treatment of head and neck space infections in children should consist of accurate physical diagnosis aided by imaging studies, empiric antibiotic therapy that covers gram-negative and beta-lactamase--producing organisms as well as gram-positive organisms and anaerobes, and timely surgical intervention, when indicated.

Infect Immun, 1995 Mar, 63(3), 899 - 902
Adhesion of nontypeable Haemophilus influenzae from blood and sputum to human tracheobronchial mucins and lactoferrin; Kubiet M et al.; Nontypeable Haemophilus influenzae strains are the most common pathogens encountered in patients with chronic bronchitis . These organisms chronically colonize the airways of patients and occasionally cause bacteremia . Nontypeable H . influenzae strains have been demonstrated microscopically to bind to mucus, but quantitative studies of adhesion have not been published to date . We have therefore developed a reproducible microtiter plate assay to study mucin binding and have examined the adhesion of sputum and blood strains of nontypeable H . influenzae . The assay is similar to that described for Pseudomonas aeruginosa (S . Vishwanath and R . Ramphal, Infect . Immun . 45:197-202, 1984), but notably 2% Tween 20 is used to desorb bacteria from the wells to quantitate bacterial binding . Using a standard strain, we have established that 1 h of incubation is optimum with an inoculum of < or = 5 x 10(8) CFU/ml . The standard strain binds to bronchitic and cystic fibrosis mucins equally well but binds less to bronchiectasis mucins . It does not bind to bovine serum albumin or fetuin . We have also examined the levels of adhesion of freshly isolated sputum and bacteremia strains and find very significant differences in adhesion . Blood strains bound six to seven times less than sputum strains ({13.8 +/- 7} x 10(2) per well versus {102 +/- 43} x 10(2); P < 0.001) . Studies with adhesion to lactoferrin, another glycosylated protein, revealed variable binding of respiratory strains but marked binding of blood strains compared with mucin . An isogenic pair of respiratory and blood isolates was examined by electron microscopy but did not show surface differences . We speculate that bacteremic strains studied may have masked, lost, or downregulated adhesin production to allow them to escape from mucins or upregulated adhesins for lactoferrin to invade the bloodstream.

Eur Respir J, 1995 Mar, 8(3), 398 - 402
Efficacy of a three day course of azithromycin in moderately severe community-acquired pneumonia; Rizzato G et al.; This study was designed to evaluate the efficacy of a 3 day course of azithromycin in low to moderately severe community-acquired pneumonia . Forty patients with low to moderately severe community-acquired pneumonia (29 males, 11 females, mean age 46 +/- 17 yrs; 20 pretreated with betalactams for 2-10 days with no results before admission to hospital; 18 with evidence of co-morbidity) were enrolled in an open, randomized study with azithromycin, 500 mg q.d . oral therapy for 3 days, versus clarithromycin, 250 mg b.i.d . oral therapy for 10 +/- 2 days . The aetiology of pneumonia was identified in 18 patients by serology (nine Mycoplasma pneumoniae, four Chlamydia pneumoniae, five Legionella pneumophila; one patient with chlamydial infection also had Klebsiella pneumoniae bacteraemia) . A presumptive aetiological diagnosis was obtained with sputum culture in three other patients (one Haemophilus influenzae, two Haemophilus parainfluenzae), all strains were sole isolates with 10(8) Colony forming units (CFU), and with Gram stain in one patient with Streptococcus pneumoniae . All patients in the azithromycin group (one after a second 3 day course), and all but two (of those available for evaluation) of the clarithromycin group were cured . Defervescence occurred after 2.6 +/- 1.6 days, and chest roentgenogram cleared after 8.9 +/- 3.3 days, with no difference between the two groups . Tolerance was good, and there were no withdrawals from therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

J Periodontal Res, 1995 Mar, 30(2), 88 - 96
Succession of putative peri-implant pathogens after root-form and plate-form implant placement in partially dentate adult monkeys; Eke PI et al.; This report describes the succession of putative peri-implant pathogens in partially dentate monkeys after dental implantation and prosthetic reconstruction . Tooth and implant (6 root-end form, 4 blade-vent implants) sites in eight monkeys were monitored microbiologically and clinically during the pre-implant stage, abutment connection stage, bridge placement stage, and three and six months after the bridge placement stage . Tooth and implant sites were cleaned monthly post-extraction . Microbiological studies included dark field microscopy, selective and non-selective culture, and primary phenotypic characterization of culture isolates . After implant surgery, the median proportion of several putative peri-implant pathogens studied were significantly elevated . Following fixture placement, P . intermedia replaced P . melaninogenica as the predominant Black Pigmented Anaerobic Bacilli (BPAB) in the mouth . After abutment connection stage, levels of P . intermedia, A . actinomycetemcomitans, F . nucleatun, Haemophilus sp . and spirochetes were significantly elevated at implant and tooth sites . Three months after bridge installations, P . intermedia and A . actinomycetemcomitans remained significantly elevated at implant sites . At six months after bridge installation, levels of P . intermedia, F . nucleatum and A . actinomycetemcomitans declined significantly relative to levels at three months . Porphyromonas sp . and spirochetes were not significantly elevated although their levels correlated with gingival redness . P . intermedia, Porphyromonas sp . and spirochetes levels correlated significantly with probing depth . Correlation was detected between P . gingivalis and spirochetes; and between A . actinomycetemcomitans and F . nucleatum . Our studies show a transitional increase in levels of several organisms resembling putative pathogens of human peri-implant infection, associated with implant placements in partially edentulous mouths and supports early prophylactic interventions to control their levels.

Trends Microbiol, 1995 Mar, 3(3), 87 - 92
Haemophilus ducreyi: pathogenesis and protective immunity; Lagergard T; Haemophilus ducreyi is the etiological agent of chancroid, a sexually transmitted disease that is common in developing countries and that has characteristic genital mucocutaneous lesions . The adherence and growth of bacteria on the surface of eukaryotic cells, and the production of cytotoxin(s) result in cell damage that may be responsible for the development of ulcers . The mechanisms for protective immunity in chancroid are unclear, but both humoral and cell-mediated mechanisms may be involved.

Pediatr Infect Dis J, 1995 Mar, 14(3), 183 - 8
Persistent acute otitis media: II . Antimicrobial treatment; Pichichero ME et al.; In this three-year prospective study, 137 children with acute otitis media (AOM) that had not responded after one or two empiric antimicrobial treatment courses (termed persistent AOM) underwent tympanocentesis to determine additional antimicrobial therapy based on in vitro susceptibility testing of the bacterial isolate(s) . One hundred eleven children with AOM not previously treated are described for comparison . In the persistent AOM group middle ear aspirates grew Streptococcus pneumoniae (24%), Haemophilus influenzae (7%), Brahamella catarrhalis (7%), Streptococcus pyogenes (6%), Staphylococcus aureus (5%), two pathogens (3%) or no bacterial growth (49%); pathogens in previously untreated AOM were similar but fewer patients (30%) had no bacterial growth . After tympanocentesis additional antimicrobial therapy for persistent AOM patients utilizing drugs shown to be effective in vitro against the isolated pathogen failed to produce clinical resolution of infection in 27 (28%) of ears . Differing clinical efficacy was observed with various antimicrobials: amoxicillin (57% failure); trimethoprim/sulfamethoxazole (75% failure); cefaclor (37% failure); cefixime (23% failure); amoxicillin/clavulanate (12% failure); and cefuroxime axetil (13% failure) . Presumptive clinical cure for previously untreated AOM patients was similar to that for untreated AOM except for fewer amoxicillin failures (30%) . We conclude that clinical failure in persistent AOM occurs (1) even when no pathogen is isolated from tympanocentesis (50% of patients) and (2) despite demonstrated in vitro activity against culture-proved pathogens.

Pediatr Infect Dis J, 1995 Mar, 14(3), 178 - 83
Persistent acute otitis media: I . Causative pathogens; Pichichero ME et al.; In this prospective study tympanocentesis was performed to determine the pathogens isolated from middle ear fluid of 200 ears in 137 children with acute otitis media (AOM) which had not responded after one or two empiric antimicrobial treatment courses (termed persistent AOM) . For comparison tympanocentesis from 154 ears in 111 children with AOM not previously treated are described . Patients were enrolled from October, 1989, until September, 1992 . In the persistent AOM group amoxicillin and trimethoprim/sulfamethoxazole were the most frequently used antimicrobials before tympanocentesis . Middle ear aspirates produced no pathogenic bacterial growth in 49% of persistent AOM patients, Streptococcus pneumoniae in 24%, Haemophilus influenzae in 7%, Branhamella catarrhalis in 7%, Streptococcus pyogenes in 6%, Staphylococcus aureus in 5% and two pathogens in 3% . Two (18%) of 11 S . pneumoniae isolates tested were penicillin-resistant; 1 was intermediate and 1 was highly resistant . Ten (83%) of 12 H . influenzae and all of 11 B . catarrhalis AOM isolates produced beta-lactamase . In comparison previously untreated AOM patients produced no bacterial growth from tympanocentesis in 30%, S . pneumoniae in 36% (8% penicillin-resistant), H . influenaze in 13% (44% beta-lactamase-producing) and B . catarrhalis in 11% (85% beta-lactamase producing) . AOM which is persistent after initial empiric antimicrobial therapy may be caused by middle ear inflammation after bacteria are killed or involve penicillin-resistant S . pneumoniae, beta-lactamase-producing H . influenzae or B . catarrhalis more commonly than occurs in AOM which has not been recently treated.

Clin Infect Dis, 1995 Mar, 20(3), 685 - 90
Steroid therapy for bacterial meningitis; Schaad UB et al.; Routine dexamethasone therapy for bacterial meningitis in pediatric patients is controversial . Two experts debated this topic at the 1993 meeting of the Infectious Diseases Society of America . Both experts agreed that for management of Haemophilus influenzae meningitis, dexamethasone significantly reduced sensorineural hearing loss and probably reduced other long-term sequelae . Because relatively few patients with pneumococcal and meningococcal meningitis have been studied, no conclusions could be reached regarding the effectiveness of dexamethasone . Dr . Urs Schaad emphasized the impressive anti-inflammatory effects of dexamethasone in experimental pneumococcal meningitis and the lack of any adverse events when given to children for 2 or 4 days . He recommended routine use of dexamethasone in treating pediatric patients with bacterial meningitis . Dr . Sheldon Kaplan expressed concern regarding the effectiveness of steroids in treating pneumococcal meningitis, especially when penicillin-resistant and cephalosporin-resistant isolates are present, and he addressed the question of the long-term effects of administration of dexamethasone in children with viral meningitis . He advised against the routine use of dexamethasone for non-H . influenzae meningitis.

Arch Pediatr, 1995 Mar, 2(3), 249 - 54
{Haemophilus influenzae: colonization and infection}; Borderon JC; Haemophilus influenzae can be demonstrated as a saprophyte in more than two-thirds of children, and almost as frequently in adults . Noncapsulated strains are more frequent than capsulated type b strains which are found in 5% of the samples . Other capsulated strains are rare . Transmission is made easier with close contact (daycare nurseries, home) . Colonization is the result of adherence to nasopharyngeal epithelial cells, although characterized adhesion factors cannot be demonstrated for all strains (pili, adhesins, secretory IgA1 protease) . Systemic infection is the result of the invasion of pharyngeal epithelium, made easier by upper respiratory tract infection . There is a risk of meningitis for high level bacteremia (> or = 10(5) CFU/ml) . Risk factors are: age (child < 5 years), alteration of reticuloendothelial system, agammaglobulinemia . Anti-Haemophilus type b vaccine prevents nearly all infections, and suppresses or sharply reduces colonization.

J Clin Pathol, 1995 Mar, 48(3), 206 - 9
Avidity of specific IgG antibodies elicited by immunisation against Haemophilus influenzae type b; Agbarakwe AE et al.; AIM--To investigate the avidity of specific IgG polyribosyl ribitol phosphate (PRP) antibodies induced by three Haemophilus influenzae type b (Hib) conjugate vaccines: PRP-meningococcal outer membrane protein complex (PRP-OMP), PRP-non-toxic mutant diphtheria toxin, CRM197 (HbOC) and PRP-tetanus toxoid (PRP-T) . METHODS--One hundred and ten infants were immunised with one of the vaccines at two, three and four months of age . Blood samples were taken after each vaccination and serum stored at -20 degrees C . Serum samples collected after the third course (that is, at five months of age) were submitted to antibody avidity assessment, using a urea enzyme linked immunosorbent assay (ELISA) . RESULTS--All three conjugate vaccines elicited IgG PRP antibodies of high median avidity . The resultant antibody populations were heterogeneous with regard to avidity, which in turn was independent of PRP antibody concentration . CONCLUSIONS--With the recent findings of a correlation between bactericidal killing and affinity, our data highlight the need for a protective level to be expressed qualitatively as well as quantitatively.

J Antibiot (Tokyo), 1995 Mar, 48(3), 248 - 53
10,11,12,13-Tetrahydro derivatives of tylosin . II . Synthesis, antibacterial activity and tissue of 4'-deoxy-10,11,12,13-tetrahydrodesmycosin; Narandja A et al.; 4'-Deoxy-10,11,12,13-tetrahydrodesmycosin was prepared in six-step reactions . Antibacterial screening shows retained antibacterial spectrum of tylosin with some improvement against tylosin-sensitive Staphylococci and Haemophilus influenze . However, the pharmacokinetic data demonstrated rapid distribution from blood in tissues and prolonged maintenance in all tissues, especially in the lungs, in comparison with tylosin.

Clin Diagn Lab Immunol, 1995 Mar, 2(2), 132 - 7
Assignment of Neisseria meningitidis serogroup A and C class-specific anticapsular antibody concentrations to the new standard reference serum CDC1992; Holder PK et al.; A new standard meningococcal reference serum designated CDC1992 was prepared to replace meningococcal reference sera ECG and PB-2, which are not available in sufficient quantities for continued use as primary reference sera . CDC1992 was prepared from 14 healthy adult volunteers who underwent plasmapheresis 4 to 12 weeks postvaccination with a single dose of a Neisseria meningitidis quadrivalent polysaccharide vaccine . Total and/or class-specific meningococcal serogroup A and C anticapsular antibody concentrations (in micrograms per milliliter) were assigned to CDC1992 by using homologous and heterologous enzyme-linked immunosorbent assay (ELISA) formats . The reference serum ECG was used as a reference standard to assign total anticapsular antibody concentrations to CDC1992 by a homologous ELISA format . A heterologous ELISA format, with the Haemophilus influenzae type b standard reference serum FDA 1983, was used to assign total and class-specific antibody concentrations to CDC1992 . Alkaline phosphatase-labeled mouse anti-human monoclonal antibody conjugates were used as secondary antibodies in both ELISA formats . The total, immunoglobulin G (IgG), IgA, and IgM antibody concentrations, assigned to CDC1992 for serogroup A were 135.8, 91.8, 20.1, and 23.9 micrograms/ml, respectively, and those for serogroup C were 32.0, 24.1, 5.9, and 2.0 micrograms/ml, respectively . Meningococcal serogroup A and C antibody concentrations were in good agreement when homologous and heterologous ELISA format results were compared . Total and class-specific serogroup A and C antibody concentrations were determined in six adult quality control serum samples from the Centers for Disease Control and Prevention by using the homologous ELISA and our assigned antibody concentrations for CDC1992 . Antibody concentrations in reference sera ECG and PB-2 were measured in order to provide a historical link to previous studies . The general acceptance of CDC1992 as the standard reference serum and the assigned antibody concentrations will allow investigators to compare antibody levels in serum to those in a single reference preparation.

Thorax, 1995 Mar, 50(3), 249 - 53
Relation between beta-lactamase producing bacteria and patient characteristics in chronic obstructive pulmonary disease (COPD); Sportel JH et al.; BACKGROUND--In addition to bronchodilator and anti-inflammatory therapy, exacerbations in patients with chronic obstructive pulmonary disease (COPD) are often treated with antibiotics . Haemophilus influenzae and Moraxella (Branhamella) catarrhalis, two important respiratory pathogens, may produce beta-lactamase which makes them resistant to ampicillin . Surveillance studies conducted in various countries have shown an increasing incidence of these beta-lactamase producing bacteria . Although this may simply be a consequence of the increasing use of antibiotics, it is possible that other factors are important . A study was undertaken to investigate whether clinical factors are related to the presence of beta-lactamase forming bacteria in the sputum of patients with COPD . METHODS--One hundred patients with COPD aged over 40 years were sequentially selected from an outpatient clinic on the basis of sputum culture results . Fifty had beta-lactamase positive (beta L+) and 50 had beta-lactamase negative (beta L-) bacteria in their sputum . Patients were included only if sputum culture results yielded one pathogen . The files of these patients were investigated for possible causative factors present during the two preceding years . RESULTS--Both groups were almost identical in terms of lung function, maintenance medication, and smoking history . The total number of antibiotic courses in the beta L+ group was higher, as were individual courses of cephalosporins, tetracyclines, and macrolides . The number of patients admitted to hospital was higher in the beta L+ group, but admissions were of equal duration in both groups . Patients admitted to hospital had poorer lung function . Risk factors for beta-lactamase producing bacteria were identified by logistic regression analysis which revealed an odds ratio for one course of antibiotics of 1.15 (95% CI 1.04 to 1.28) . CONCLUSIONS--An increased number of antibiotic courses is related to a higher incidence of beta-lactamase producing bacteria and more patients had hospital admissions in the beta L+ group . beta-lactamase stable antibiotics were used more frequently in the beta L+ group, probably because prescribing was adapted to the presence of beta-lactamase producing bacteria . No other differences were found between the beta L+ and beta L- groups.

Diagn Microbiol Infect Dis, 1995 Mar, 21(3), 175 - 9
Tentative criteria for determining the in vitro susceptibilities of Haemophilus influenzae, including quality control parameters, to two fluoroquinolones (grepafloxacin and PD 131628); Sewell DL et al.; Grepafloxacin (OPC 17116) and PD 131628 were evaluated against 150 Haemophilus influenzae isolates to propose susceptibility testing criteria for both broth dilution and disk diffusion procedures using haemophilus test medium . Grepafloxacin-susceptible isolates are defined as those for which minimum inhibitory concentrations (MICs) are < or = 0.06 micrograms/ml and zones of inhibition are > or = 27 mm . PD 131628-susceptible strains of H . influenzae included those that exhibited MICs < or = 0.03 micrograms/ml, and the zones were > or = 32 mm . All MICs were well below concentrations that can be achieved in the blood and tissues of patients treated with either study drug . Criteria for defining a resistant category cannot be determined until strains with elevated MICs are available for study . The proposed quality control guidelines for H . influenzae ATCC 49247 and the disk test are 32-39 mm in diameter for grepafloxacin and 34-42 mm for PD 131628 . The preliminary broth microdilution MIC control limits for this strain are 0.002-0.016 micrograms/ml for grepafloxacin and 0.002-0.008 micrograms/ml for PD 131628.

Infection, 1995 Mar-Apr, 23(2), 113 - 8
Five days of antibacterial therapy for bacterial meningitis in children?
Lutsar I, Gontmacher A, Narska M, Ruutel V, Topman M, Ilves P, Siirde T, Beilmann A.
We evaluated the effectiveness of 5-day antibacterial therapy for bacterial meningitis in children . The study group included 26 children from 2 months to 15 years of age, admitted with microbiologically confirmed bacterial meningitis in 1990-1993 and treated for 5 days . A historical comparison group of 49 patients treated for 8 to 15 days was used . Penicillin monotherapy (300 mg/kg body weight) was used for meningococcal and pneumococcal meningitis and ampicillin (300 mg/kg body weight) for Haemophilus influenzae b meningitis . On day 5 of therapy the activity of aspartate aminotransferase (AST), lactic dehydrogenase (LDH), creatine phosphokinase (CPK) and gamma-glutamyl-transpeptidase (gamma GT) in the CSF was determined by photocolorimetric assay and the concentration of creatine kinase BB (CK-BB) by ELISA . IL-6 was analysed using EIA technique and a cerebral ultrasound was performed at the time of the termination of the antibacterial therapy . The mean follow-up time was 1.3 years for children in the study group and 3.2 in the control group . The time of hospitalisation was shorter in children treated for 5 days (p < 0.005) . Complete clinical recovery was 81% in the study group and 66% in the comparison group at the time of the termination of antibacterial therapy . No relapses occurred . The activity of AST, CPK, LDH, and gamma GT in the CSF had returned to normal by the 5th day of therapy, but almost a 7-fold higher concentration of CK-BB was registered . The concentration of IL-6 in the CSF decreased with the therapy from 1,800 pg/ml to 685 pg/ml but still remained high.(ABSTRACT TRUNCATED AT 250 WORDS)

Zentralbl Veterinarmed B, 1995 Mar, 42(1), 59 - 63
Isolation of the major outer-membrane protein of Actinobacillus pleuropneumoniae and Haemophilus parasuis; Hartmann L et al.; A polyclonal antibody against the 35 kDa major outer-membrane protein of Pasteurella multocida cross-reacted with the 40 kDa major outer-membrane protein of Actinobacillus pleuropneumoniae and the 42 kDa major outer-membrane protein of Haemophilus parasuis . The N-terminal amino-acid sequences of these proteins revealed a strong homology with the putative 35 kDa porin protein of Pasteurella multocida (66.7 and 76.2%, respectively) . Significant homologies were also evident between the 40 kDa and the 42 kDa protein (76.2%), and with non-specific porins of gram-negative bacteria.

Lancet, 1995 Feb 4, 345(8945), 291 - 2
Effect of neonatal circumcision on pain responses during vaccination in boys; Taddio A et al.; Using data from one of our randomised trials, we investigated post-hoc whether male neonatal circumcision is associated with a greater pain response to routine vaccination at 4 or 6 months . Pain response during routine vaccination with diphtheria-pertussis-tetanus (DPT) alone or DPT followed by Haemophilus influenzae type b conjugate (HIB) was scored blind . 42 boys received DPT and 18 also received HIB . After DPT, median visual analogue scores by an observer were higher in the circumcised group (40 vs 26 mm, p = 0.03) . After HIB, circumcised infants had higher behavioural pain scores (8 vs 6, p = 0.01) and cried longer (53 vs 19 s, p = 0.02) . Thus neonatal circumcision may affect pain response several months after the event.

Epidemiol Infect, 1995 Feb, 114(1), 93 - 103
Incidence and spread of Haemophilus influenzae on an Antarctic base determined using the polymerase chain reaction; Hobson RP et al.; A PCR-based method of detecting Haemophilus influenzae in cultures inoculated from throat swabs was evaluated using samples from groups of laboratory staff and medical students and then applied to samples originating from the closed human community of an Antarctic research station . Suitable PCR primers to an H . influenzae gene (ompP2) were used to amplify the gene from DNA preparations made from mixed growth on chocolate agar with added vancomycin . PCR product was reamplified and subjected to restriction endonuclease digestion to allow temporal and spatial mapping of strains over an 8-month period . Eleven different strains of H . influenzae were detected . One particular strain was detected in a third of the base members.

J Pediatr, 1995 Feb, 126(2), 206 - 11
Enhanced antibody responses in infants given different sequences of heterogeneous Haemophilus influenzae type b conjugate vaccines; Greenberg DP et al.; To evaluate the safety and immunogenicity of differing sequences of heterogeneous Haemophilus influenzae type b (Hib) conjugate vaccines, we randomly assigned 300 infants to one of six vaccination schedules . At 2, 4, and 6 months of age, subjects were given single or heterogeneous vaccines: Hib polysaccharide (PRP) conjugated to mutant diphtheria toxin (HbOC), PRP conjugated to outer-membrane protein of Neisseria meningitidis (PRP-OMP), or PRP conjugated to tetanus toxoid (PRP-T) . No serious reactions were attributable to immunization with heterogeneous vaccines, and there were few significant differences in the rates of minor adverse reactions among groups . PRP-OMP was the only vaccine that induced an antibody response after the first dose, but significant booster responses were not seen after the second and third doses . Subjects given PRP-T vaccine responded well after two doses, but three doses of HbOC vaccine were needed for an equivalent antibody response . All the Hib vaccine schedules evaluated were immunogenic, and schedules initiated by PRP-OMP vaccine at 2 months of age, followed by two doses of either HbOC or PRP-T vaccine at 4 and 6 months of age, induced the highest antibody levels after each dose . Such schedules may be the best for protecting infants and children who are at greatest risk of having invasive Hib disease, such as American Indian children.

J Pediatr, 1995 Feb, 126(2), 198 - 205
Effect of neonatal immunization with diphtheria and tetanus toxoids on antibody responses to Haemophilus influenzae type b conjugate vaccines; Lieberman JM et al.; We randomly assigned 150 newborn infants to receive diphtheria and tetanus toxoids (DT) or Hib oligosaccharide conjugate (HbOC) at birth to determine whether exposure to the Haemophilus influenzae type b (Hib) conjugate vaccines' carrier proteins would enhance immune responses to subsequent administrations of HbOC or PRP-tetanus toxoid conjugate (PRP-T) at 2, 4, and 6 months of age . Their antibody responses were compared with those of 100 children immunized with HbOC or PRP-T beginning at 2 months of age . No serious adverse reactions were associated with neonatal vaccination . Administration of HbOC at birth did not lead to earlier or higher antibody levels . Newborn immunization with DT did not prime children for enhanced antibody responses . Moreover, Hib antibody levels were lower in DT-primed children than in children immunized beginning at 2 months of age . Diphtheria antibody levels, but not tetanus antibody levels, were also lower in children immunized with DT at birth . We conclude that neonatal immunization with Hib conjugate vaccines is not a means to provide earlier protection against invasive Hib disease . Newborn DT administration does not enhance subsequent antibody responses to Hib conjugate vaccines, and may lead to suppression of Hib and diphtheria antibody responses.

J Infect Dis, 1995 Feb, 171(2), 451 - 5
Sexually transmitted diseases and human immunodeficiency virus control in Malawi: a field study of genital ulcer disease; Behets FM et al.; Men with genital ulcer disease (GUD) attending a clinic in Malawi were evaluated and treated with one of five drug regimens . Haemophilus ducreyi was isolated from 204 (26.2%) of 778 patients . Of 677 men, 198 (29.2%) had treponemes detected in ulcer material by direct immunofluorescence or had rapid plasma reagin reactivity of > or = 1:8 . Human immunodeficiency virus type 1 (HIV-1) seroprevalence was 58.9% overall and 75.8% among patients reporting a history of GUD (P < .001) . By logistic regression analysis, HIV-1 seropositivity was shown to impair ulcer healing (P = .003) . Treatment failure rates for culture-proven chancroid were 19% for trimethoprim-sulfamethoxazole, 12.9% and 7.4%, respectively, for low- and high-dose erythromycin regimens, and 8.3% and 0, respectively, for low- and high-dose ciprofloxacin regimens . Herpes antigen was detected by EIA in 6 (23.1%) of 26 nonhealing ulcers . In Malawi, GUD should be managed as a syndrome to assure treatment of both syphilis and chancroid.

J Infect Dis, 1995 Feb, 171(2), 342 - 9
Hematogenous bacterial meningitis in an intercellular adhesion molecule-1-deficient infant mouse model; Tan TQ et al.; Mice genetically deficient in the gene encoding for intercellular adhesion molecule-1 (ICAM-1) production were compared with wild-type mice after injection with Haemophilus influenzae type b (Hib) or Streptococcus pneumoniae . The incidence of Hib bacteremia was greater in the ICAM-1-deficient mice than wild-type mice (P = .007), but mortality was greater for wild-type mice at 24 h (P = .03) . In contrast, the incidence of S . pneumoniae bacteremia was equivalent but mortality was greater in ICAM-1-deficient mice at 24 h (P = .0003) . More ICAM-1-deficient mice had cerebrospinal fluid cultures (CSF) positive for Hib (P = .04), whereas all animals at sacrifice had CSF cultures positive for S . pneumoniae . CSF white blood cell counts and histology of the meninges and cochlea were no different between groups for either organism . ICAM-1 deficiency may be protective early in Hib infection but has a detrimental effect in S . pneumoniae infection.

Infect Immun, 1995 Feb, 63(2), 710 - 3
Utilization of transferrin-bound iron by Haemophilus influenzae requires an intact tonB gene; Jarosik GP et al.; Haemophilus influenzae can utilize iron-loaded human transferrin as an iron source for growth in vitro . H . influenzae tonB mutants, containing a chloramphenicol acetyltransferase gene within their tonB genes, could bind iron-charged human transferrin to their cell surfaces, but they were unable to utilize this serum glycoprotein as the sole source of iron for growth in vitro . In contrast, these tonB mutants were able to utilize an iron chelate (ferric ammonium citrate) for growth . Transformation of a tonB mutant with a plasmid encoding a wild-type H . influenzae tonB gene restored the ability of a tonB mutant to utilize iron-charged human transferrin . These results indicate that the uptake of iron from human transferrin by H . influenzae is a TonB-dependent process.

Infect Immun, 1995 Feb, 63(2), 696 - 9
The gene encoding protein D (hpd) is highly conserved among Haemophilus influenzae type b and nontypeable strains; Song XM et al.; The molecular conservation of a surface-exposed lipoprotein, protein D, of Haemophilus influenzae was studied by cloning and sequencing of the gene encoding protein D from three encapsulated type b strains and three nontypeable strains of H . influenzae . These nucleotide sequences were analyzed with previously reported sequences from one type b strain and one nontypeable strain . The nucleotide sequences and the deduced amino acid sequences for protein D were highly conserved . The deduced amino acid sequence (364 amino acids) of protein D from six strains differed only in two amino acids near the C-terminal end . The remaining two strains, one type b and one nontypeable, differed from the consensus sequence in 7 amino acids each . Protein D is 64 and 36% identical and 77 and 56% similar to the glycerophosphodiester phosphodiesterases (GlpQ) of Escherichia coli and Bacillus subtilis.

Mol Microbiol, 1995 Feb, 15(3), 495 - 506
Comparative characterization of the iga gene encoding IgA1 protease in Neisseria meningitidis, Neisseria gonorrhoeae and Haemophilus influenzae; Lomholt H et al.; Cloning and sequencing of the IgA1 protease gene (iga) from Neisseria meningitidis strain HF13 showed an overall structure equivalent to iga genes from Neisseria gonorrhoeae and Haemophilus influenzae, although no region corresponding to the gonococcal alpha-peptide was evident . An additional 18 N . meningitidis and 3 H . influenzae iga genes were amplified by the polymerase chain reaction technique and sequenced corresponding approximately to the N-terminal half of the mature enzyme . Comparative analyses of a total of 29 iga genes showed that pathogenic Neisseria have iga genes with a significantly lower degree of heterogeneity than H . influenzae iga genes . Recombinational events indicated by mosaic-like structures corresponding to those found among N . gonorrhoeae protease genes were detected among N . meningitidis iga genes . One region showed characteristic differences in sequence and length which correlated with each of the different cleavage specificities . Meningococci were extremely conserved in this region with no evidence of recombination between isolates of different cleavage specificities . Sequences further downstream showed no obvious relationship with enzyme cleavage type . This region consisted of conserved areas interspersed with highly variable areas . Amino acid sequence homologies in the variable regions of meningococci reflected the antigenic types defined by using polyclonal neutralizing antibodies.

Aust N Z J Obstet Gynaecol, 1995 Feb, 35(1), 102 - 3
Neonatal infection due to Haemophilus influenzae biotype IV; Webster PB et al.; Neonatal infection due to Haemophilus influenzae has several clinical similarities to infection by the more common Streptococcus agalactiae (Strep group B) . A high frequency of H . influenzae biotype IV in association with genital, maternal and neonatal infections has been reported in the literature, suggesting this biotype has an affinity for the female genital tract . Cefotaxime should be considered as part of the treatment regimen when this organism is suspected because of the emerging resistance of H . influenzae to ampicillin . We present a case of H . influenzae biotype IV infection in a premature (32 weeks) neonate.

Acta Paediatr, 1995 Feb, 84(2), 173 - 6
Invasive Haemophilus influenzae type b infections in children hospitalized in Hong Kong, 1986-1990 . Hong Kong Hib Study Group; Lau YL et al.; A 5-year territory-wide retrospective survey of invasive Haemophilus influenzae type b diseases was conducted in Hong Kong . Between 1986 and 1990, 57 cases (28 male) were recorded in children less than 12 years old (37 cases of meningitis, 9 of septicaemia and 11 of bacteraemic pneumonia) . The annual incidence for children less than 5 years old was 2.7 per 10(5) (95% confidence interval (CI) 2.0-3.5) . Of the 57 cases, 39 were Chinese and 18 non-Chinese (7 Vietnamese refugees, 6 Caucasians, 5 others) . The annual incidence in Vietnamese refugees less than 5 years old was 42.7 per 10(5) (95% CI 17.2-87.9), giving a relative risk of 18.5 (95% CI 8.3-41.0) . Chinese patients (68%) were under-represented as Chinese accounted for at least 94% of the population . Moreover, 14 of the 39 Chinese patients had pre-existing medical problems, compared with only 1 of the 18 non-Chinese patients patients had pre-existing medical problems, compared with only 1 of the 18 non-Chinese patients (p = 0.022).

Pediatr Infect Dis J, 1995 Feb, 14(2), 129 - 35
Antibody responses to Haemophilus influenzae type b and Streptococcus pneumoniae vaccines in children with human immunodeficiency virus infection; Gibb D et al.; Antibody responses to Haemophilus influenzae type b (Hib) conjugate (ActHIB; Pasteur Merieux) and pneumococcal (Pneumovax II; Morson) vaccines were measured in 56 infected children (VI) and 44 uninfected children (U) older than 18 months of age, born to human immunodeficiency virus-positive mothers . Preimmunization, 21% U and 20% VI had protective concentrations of anti-Hib polysaccharide antibodies . Postimmunization, 100% U and 86% VI achieved protective titers (P = 0.008) . The geometric mean increase in anti-Hib polysaccharide antibody was 7.6 (95% confidence interval, 3.5 to 16.3; P = 0.0001) times higher in U than in VI children after adjusting for age and ethnicity . Sixty-one percent U compared to 54% VI showed a 2-fold increase in antibody levels to at least one of the four pneumococcal vaccine serotypes (3, 6, 19, 23) measured (P = 0.4) . For both vaccines there was a significant trend toward poorer responses in children with acquired immunodeficiency syndrome but no correlation with age adjusted CD4 counts . These data suggest that human immunodeficiency virus-infected children should be immunized with these polysaccharide vaccines early in the course of their disease.

Jpn J Antibiot, 1995 Feb, 48(2), 278 - 83
{Clinical studies on minocycline in infantile acute pharyngolaryngitis with cough}; Tomiyama M; Among cases of infantile acute pharyngolaryngitis with cough as a chief complaint, 21 cases that the involvement of bacterial infections has been demonstrated were given minocycline (MINO) and the effectiveness and safety of MINO were investigated . 1 . Regarding the clinical effectiveness, the number of cases assessed as markedly effective was 9 (43%) and that as effective was 8 (38%), so that the effectiveness rate was 81%, and particularly, in the infections caused by Haemophilus influenzae, MINO showed a high effectiveness . 2 . Five strains of Streptococcus pneumoniae, 2 strains of Streptococcus pyogenes and 16 strains of H . influenzae, a total of 23 strains of pathogenic bacteria were isolated, and MINO showed high activities against not less than 80% of these strains . 3 . The bacteriological effect in terms of the rate of eradication was 71%, and that of H . influenzae was as high as 88%, while S . pneumoniae remained in 3 of 5 cases . 4 . Adverse reactions were observed in 2 cases (10%), 1 case each of abdominal pain and stomatitis, and both of them were improved after the treatment termination . 5 . Regarding the usefulness, which was comprehensively assessed using clinical effectiveness and safety as criteria, the number of cases evaluated satisfactorily useful was 8 (38%) and that as useful was 8 (38%), so that the overall usefulness rate was 76% . From the above results, it was confirmed that MINO is a drug having high efficacy and safety against infantile acute pharyngolaryngitis with cough as a chief complaint caused by H . influenzae.(ABSTRACT TRUNCATED AT 250 WORDS)

Jpn J Antibiot, 1995 Feb, 48(2), 229 - 37
{Clinical and laboratory studies on SY5555 in pediatric infectious diseases}; Wakiguchi H et al.; Clinical effects of SY5555 dry syrup, a new oral penem antibiotic, were analysed in 20 children with various bacterial infections . Ages of the patients varied from 8 months to 14 years . Doses of SY5555 were varied from 12.8 mg/kg/day to 30.5 mg/kg/day, and it was administered in 3 divided dosages . Clinical efficacy rates were as follows; 6/7 in acute bronchitis, 5/5 in pharyngotonsillitis, 3/3 in acute otitis media and 2/2 in cystitis and 3/3 in impetigo contagiosa . The overall rate was 95.0% (19/20) . Bacteriologically, eradications were obtained with 1/2 strains of Streptococcus pyogenes, 3/3 of Staphylococcus aureus, 1/1 of Haemophilus influenzae, and each of Staphylococcus epidermidis, Haemophilus parainfluenzae, coagulase-negative staphylococci and Serratia marcescens . Diarrhea was observed in 1 patient . And elevated eosinophiles or GPT was observed in one patient each . In vivo pharmacokinetics of SY5555 was examined in 2 cases . Peak plasma levels were observed at 1 hour after dosage in one patient and at 2 hours in another upon oral administration of 8.3 mg/kg of SY5555, and peak levels were 2.44 and 1.38 micrograms/ml respectively . Half-lives of SY5555 were 1.39 and 0.59 hr . Concentrations of SY5555 in urine after administration were 70.2 (2-4 hrs.) to 91.0 (0-5 hrs.) micrograms/ml, respectively . SY5555 dry syrup is considered as an useful and safe antibiotic in treating the infectious diseases in children.

Jpn J Antibiot, 1995 Feb, 48(2), 205 - 9
{Clinical study of SY5555 dry syrup in the pediatric field}; Haruta T et al.; SY5555 dry syrup (powder to be dissolved before use) was clinically used in pediatric patients . The following results were obtained: 1 . The subjects were 6 pediatric patients including 1 case each with pharyngitis, tonsillitis, lacunar tonsillitis and impetigo contagiosa and 2 cases with scarlet fever . The drug was administered at a daily dose of 14.5-29.0 mg/kg divided into 3 dosages . The clinical results were excellent in 5 cases and good in 1 case with an efficacy rate of 100% . 2 . Identified bacteria included 3 strains of Haemophilus influenzae, 2 strains of Streptococcus pyogenes and 1 strain of Staphylococcus aureus . Five strains were eradicated but 1 strain still remained with an bacteriological eradication rate of 83.3% . 3 . No side effects were observed throughout the study period . In laboratory test results, elevated eosinophil count was observed in only 1 case . 4 . Patients' compliance was good in general . 5 . Based on the results mentioned above, the drug was considered to be a useful new oral antibiotic in the pediatric field.

Pediatr Res, 1995 Feb, 37(2), 155 - 9
Activation of the neutrophil bactericidal activity for nontypable Haemophilus influenzae by tumor necrosis factor and lymphotoxin; Tan AM et al.; Previous studies have suggested that, in vivo, activated T lymphocytes and neutrophils are important in immunity to nontypable Haemophilus influenzae . We now extend this work by showing that neutrophils pretreated with products of activated T lymphocytes or activated macrophages show significantly enhanced killing of nontypable H . influenzae . Lymphotoxin, a product of activated T lymphocytes, significantly enhanced the neutrophil-mediated killing of nontypable H . influenzae, and tumor necrosis factor, produced by activated T lymphocytes as well as macrophages stimulated by activated T lymphocytes, also significantly increased the bactericidal activity of neutrophils . These cytokine-induced effects were seen with short pretreatment times of neutrophils and were maximal by 30 min . The killing of H . influenzae by neutrophils required the presence of heat-labile opsonins . In the absence of these opsonins, both tumor necrosis factor and lymphotoxin were unable to promote the killing of the bacteria by neutrophils . Furthermore, the results showed that tumor necrosis factor-primed neutrophils displayed significantly increased expression of CR3 and CR4 that was associated with increased phagocytosis of complement-opsonized nontypable H . influenzae . These cytokines may play an important role in immunity toward nontypable H . influenzae by stimulating neutrophil bactericidal activity.

Curr Opin Pediatr, 1995 Feb, 7(1), 36 - 41
The spleen in children; Lane PA; The spleen contributes importantly to the normal and pathologic removal of blood cells from the circulation and to defense against infection with encapsulated bacteria . Surgical splenectomy provides efficacious treatment for a number of pediatric disorders but is associated with perioperative morbidity and a life-long risk of overwhelming infection . Alternatives to conventional splenectomy include laparoscopic splenectomy, partial splenectomy, partial splenic embolization, and autologous splenic transplantation . Sickle cell disease is the most common cause of functional asplenia in children . Asplenia develops during infancy in many infants with sickle cell anemia, and prophylactic penicillin markedly reduces mortality from pneumococcal infection . In contrast, recent evidence suggests that children with sickle-hemoglobin C disease do not develop functional asplenia before 3 to 4 years of age and thus may not benefit from penicillin prophylaxis . Recommendations for the treatment of asplenic patients include pneumococcal, Haemophilus influenzae type b, and meningococcal immunizations, antimicrobial prophylaxis for selected patients, and prompt evaluation and aggressive treatment of acute febrile illness.

Microb Pathog, 1995 Feb, 18(2), 81 - 96
Investigations into the molecular basis of meningococcal toxicity for human endothelial and epithelial cells: the synergistic effect of LPS and pili; Dunn KL et al.; Using human umbilical vein endothelial cells as an in vitro model of toxicity, it was found that Neisseria meningitidis, Neisseria gonorrhoeae, Neisseria lactamica and Neisseria sicca caused damage to these cells, in contrast to the lack of cytotoxicity exhibited by Haemophilus influenzae type b . N . meningitidis was also found to be toxic for human epithelial cells . The major toxic factor of N . meningitidis was found to be a heat-stable component of outer membrane vesicles, and could be inhibited by polymyxin B, suggesting that lipopolysaccharide plays a major role in toxicity . However, the toxicity mediated by lipopolysaccharide was modulated significantly by pilus-dependent adherence . Intra-strain variants expressing altered pilins which exhibited different levels of adherence to epithelial and endothelial cells were used to study the role of pilus . The degree of toxicity observed correlated with their relative level of adherence to cultured cells . In contrast, Opc-dependent increased adherence did not result in increased toxicity for endothelial cells, suggesting that pili have a synergistic effect, contributing to the overall damage.

Microb Pathog, 1995 Feb, 18(2), 129 - 40
Phenotypic variation in Haemophilus influenzae: the interrelationship of colony opacity, capsule and lipopolysaccharide; Roche RJ et al.; H . influenzae type b strains show phase variation between opaque (O) and translucent (T) colony phenotypes . These phenotypic differences have been related to differences in virulence for infant rats . This study shows that the switch between O and T colony phenotypes is associated with variation in the amount of cell-associated capsule in the serotype b strains Rd:b+:01, RM7004 and Eagan . O colonies comprised organisms which were more serum resistant and had more cell-associated polyribosyl ribitol phosphate (PRP) than organisms from T colonies . Strain Rd, the non-encapsulated parent of the encapsulated transformant Rd:b+:01, was constitutively translucent, consistent with its lack of capsule expression . Since previous studies had correlated O-T switching with differences in the relative molecular weight of lipopolysaccharide (LPS), LPS phenotypes of Rd and Rd:b+:01 were compared and correlated with opacity phenotype at the individual colony level . Both strains showed phase variation between higher and lower molecular weight LPS oligosaccharide structures but the prevalence of higher molecular weight LPS was greater for the capsule-deficient Rd than encapsulated Rd:b+01 . Capsule-deficient mutants of strains Rd:b+:01, RM7004 and Eagan produced constitutively translucent colonies and each had a greater prevalence of higher molecular weight LPS than their encapsulated parents . These findings indicated an incomplete association between capsular O-T phase variation and LPS expression.

J Chemother, 1995 Feb, 7(1), 50 - 4
Pulmonary penetration of ceftazidime; Cazzola M et al.; For an antibiotic to be effective in lower respiratory tract infections, it should be available in adequate concentrations in respiratory tissues and fluids . Cephalosporins usually achieve modest concentrations in the respiratory tract . In this study we have determined the pulmonary penetration of intramuscularly administered ceftazidime (a single dose of 1 g) . Levels of ceftazidime in bronchial secretions (BS), bronchial mucosa (BM), epithelial lining fluid (ELF), and serum (S) were measured by microbiological assay in 25 patients suffering from acute exacerbation of chronic bronchitis who were divided into 5 groups of 5 subjects according to sampling time (1, 2, 4, 8 and 12 hours after the administration of the antibiotic) . The peak S level was high (39.89 +/- 10.42 micrograms/ml at 1 hour) and mean S concentrations decreased slowly and were still detectable at 12 hours (1.07 +/- 0.45 microgram/ml) . In all other samples, mean concentrations were in excess of the ceftazidime minimum inhibitory concentrations (MICs) for many relevant respiratory pathogens (Haemophilus influenzae 0.15 microgram/ml; Moraxella catarrhalis 0.06 micrograms/ml; Streptococcus pneumoniae 0.15 micrograms/ml; Klebsiella pneumoniae 0.4 microgram/ml) . Concentrations in BM (7.05 +/- 2.38, 8.14 +/- 2.23, 6.40 +/- 1.63, 4.06 +/- 0.99 and 0.45 +/- 0.27 microgram/g) were higher than that in BS (6.87 +/- 1.96, 6.54 +/- 1.84, 3.52 +/- 1.23, 1.56 +/- 0.92 and 0.23 +/- 0.19 microgram/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Presse Med, 1995 Jan 21, 24(3), 189 - 94
Chemotherapy for chronic bronchitis . Controversies; Ball P et al.; Chronic bronchitis is a common inflammatory disease of the airways characterised by cough, sputum production and associated features such as dyspnoea and respiratory obstruction . It has a poor prognosis once fully developed and imposes a heavy financial burden on affected societies . Chronic bronchitis is subject to periodic exacerbations in which the role of bacterial infection and the rightful place of antibiotic therapy is only slowly emerging, largely due to the non-homogeneity of the populations under study . Haemophilus influenzae is implicated as the pathogen in more than half of all bacterial exacerbations, Streptococcus pneumoniae and Moraxella catarrhalis accounting for a further third . Viruses and mycoplasmas are also involved . Some 18-25% of patients receiving domiciliary therapy may fail to respond to initial treatment, calling into question the efficacy of antibiotics in acute exacerbations . In part this may relate to sub-optimal respiratory pharmacokinetics as most antibiotics are quite effective against sensitive respiratory pathogens in vitro . However, bacterial resistance rates against traditional agents are rising rapidly in Europe and new agents are needed to counter this threat . Paradoxically few such agents have been shown to improve on the results of amoxycillin and other standard drugs, probably because most trials include patients with exacerbations of only mild-to-moderate severity due to sensitive pathogens . Since recent large scale studies have demonstrated the efficacy of antibiotic therapy compared with placebo in defined exacerbations, use of these definitions has allowed more realistic assessment of new agents which, in terms of improved antibacterial potency and respiratory pharmacokinetics, should offer superior efficacy . Regression analysis of a large scale general practice survey in the UK has now shown the frequency of exacerbations and the presence of co-morbid conditions to correlate significantly with a poor therapeutic outcome and thus, by implication, with severity . Future trials of antibacterial chemotherapy for acute bacterial exacerbations of chronic bronchitis should incorporate such criteria so that real differences between existing and improved compounds can be assessed.

Vet Rec, 1995 Jan 14, 136(2), 32 - 5
Porcine reproductive and respiratory syndrome: clinical disease, pathology and immunosuppression; Done SH et al.; Porcine reproductive and respiratory syndrome (PRRS) was first known as blue-eared pig disease in the United Kingdom and the causative agent as 'Lelystad virus' . The disease is characterised by very variable clinical signs, including reproductive failure and respiratory disease . The respiratory syndrome is often associated with severe infection with secondary bacterial agents including Pasteurella multocida, Haemophilus parasuis and Streptococcus suis . However, some seropositive herds show no clinical signs of disease . The secondary infections may be facilitated by the destruction of circulating lymphocytes, by the destruction of the mucociliary clearance system and, most importantly, by a large reduction in the numbers of alveolar macrophages . The clinical syndrome observed in a herd may therefore depend in part upon the other diseases present.

Gene, 1995 Jan 11, 152(1), 89 - 92
Cloning and sequencing of the Haemophilus influenzae exbB and exbD genes; Jarosik GP et al.; The exbB and exbD genes of Haemophilus influenzae (Hi) were cloned and sequenced . The deduced Hi ExbB and ExbD proteins possessed 27 and 28% amino-acid identity (56 and 58% relatedness) with the Escherichia coli ExbB and ExbD proteins, respectively; two proteins which function as TonB accessory proteins during biopolymer transport . Plasmid-encoded Hi exbB and exbD partially complemented an E . coli exbB/exbD mutation.

Gene, 1995 Jan 11, 152(1), 85 - 8
Production of Haemophilus influenzae type-b porin in Escherichia coli and its folding into the trimeric form; Pullen JK et al.; The P2 protein from pathogenic Haemophilus influenzae type b (Hib) functions as a bacterial porin and is one of several immunogenic outer membrane proteins . The P2 gene was expressed in Escherichia coli and the recombinant P2 protein (re-P2) purified to facilitate functional and immunologic studies . P2 was obtained from Hib strain Eagan using PCR and the pET vectors (17b and 11a) were used to produce re-P2 at levels exceeding 30% of the total E . coli proteins . Since previous reports had indicated that P2 was toxic to E . coli, steps were taken to control the toxicity . The plasmid was stabilized by tightly controlling the synthesis of re-P2 prior to induction . Subsequent to induction, re-P2 was sequestered into inclusion bodies rather than to membrane compartments . The refolding of the denatured re-P2 into the trimeric form involved high salt and calcium ions . re-P2 was then purified to homogeneity using gel-filtration and ion-exchange chromatography.

J Biol Chem, 1995 Jan 6, 270(1), 5 - 8
Production and oxidation of indole by Haemophilus influenzae; Stull TL et al.; During growth in high concentrations of iron nitrate, H . influenzae produces compounds reactive in biochemical assays for hydroxamates . Mixing experiments established that nitrate was responsible for inducing these compounds . Analysis by 1H and 13C NMR and high resolution mass spectrometry identified the active species as 2,2-bis(3'-indolyl)indoxyl . Bacterial production of the latter compound has been previously observed only in Pseudomonas aureofaciens . A mutant defective in the production of 2,2-bis(3'-indolyl)indoxyl was constructed by marker insertion . The formation of indole and 2,2-bis (3'-indolyl)indoxyl was quantitated by reverse-phase high pressure liquid chromatography during growth in high concentrations of nitrate . The mutant produced high concentrations of indole, but only minimal amounts of 2,2-bis(3'-indolyl)indoxyl, and also proved to be defective in nitrate reduction . These data suggest that indole may function as an electron donor for nitrate reductase in H . influenzae.

Bull World Health Organ, 1995, 73(6), 761 - 7
Simple algorithms for the management of genital ulcers: evaluation in a primary health care centre in Kigali, Rwanda; Bogaerts J et al.; A cross-sectional study was conducted among 395 patients presenting with genital ulcers at a primary health care centre in Kigali, Rwanda . Using clinical data and the results of a rapid plasma reagin (RPR) test, we simulated the diagnostic outcome of two simple WHO flowcharts for the management of genital ulcers . These outcomes and a clinical diagnosis were then compared with the laboratory diagnosis based on culture for genital herpes and Haemophilus ducreyi and serology for syphilis . The prevalence of HIV infection was high (73%) but there was no difference between HIV-positive and HIV-negative patients in the clinical presentation and etiology of genital ulcer disease . The proportion of correctly managed chancroid and/or syphilis cases was 99% using a syndromic approach, 82.1% using a hierarchical algorithm including an RPR test, and 38.3% with a clinical diagnosis . In situations where no laboratory support is available, a simple syndromic approach is preferable to the clinical approach for the management of genital ulcer . If an RPR test can be included in the diagnostic strategy, patients with a reactive RPR test should be treated for both syphilis and chancroid infectionPIP: A cross-sectional study was conducted among 395 patients presenting with genital ulcers at a primary health care center in Kigali, Rwanda . Using clinical data and the results of a rapid plasma reagin (RPR) test, the authors simulated the diagnostic outcome of two simple WHO flowcharts for the management of genital ulcers . These outcomes and a clinical diagnosis were then compared with the laboratory diagnosis based on culture for genital herpes and Haemophilus ducreyi and serology for syphilis . The prevalence of HIV infection was high (73%) but there was no difference between HIV-positive and HIV-negative patients in the clinical presentation and etiology of genital ulcer disease . The proportion of correctly managed chancroid and/or syphilis cases was 99% using a syndromic approach, 82.1% using a hierarchical algorithm including an RPR test, and 38.3% with a clinical diagnosis . In situations where no laboratory support is available, a simply syndromic approach is preferable to the clinical approach for the management of genital ulcer . If an RPR test can be included in the diagnostic strategy, patients with a reactive RPR test should be treated for both syphilis and chancroid infection . (author's)

Microbios, 1995, 84(340), 187 - 94
Isolation and characterization of a Pseudomonas aeruginosa genomic DNA sequence, encoding a putative DNA helicase belonging to superfamily I; Avichezer D et al.; The isolation and characterization of a 2,122 bp DNA fragment from a Pseudomonas aeruginosa genomic library containing a 1,495 bp open reading frame (ORF) encoding a putative DNA helicase is described . The deduced amino acid (498 residues) sequence derived from this ORF, exhibited a high degree of homology to the rep and uvrD helicases of Escherichia coli (55 and 38% identities, respectively), and to those of Staphylococcus aureus and Haemophilus influenzae (43 and 39% identities, respectively), all of them belonging to superfamily I.

Aust Vet J, 1995 Jan, 72(1), 18 - 21
Characterisation of porcine haemophili isolated from Australian pigs between 1988 and 1992; Blackall PJ et al.; A total of 362 haemophili, isolated pigs throughout Australia, were characterised by phenotypic properties . Most were identified as Actinobacillus pleuro-pneumoniae (296 isolates) or Haemophilus parasuis (52 isolates) . The remaining isolates were identified as Haemophilus Taxon 'minor group' (12 isolates) and Haemophilus Taxon D (two isolates) . All 296 A pleuropneumoniae isolates were serotyped by slide agglutination and/or gel diffusion, using rabbit antisera against all 12 recognised serovars . Of these, only 156 (52.7%) could be assigned to a single serovar as follows: serovar 1-85 isolates, serovar 2-4 isolates, serovar 3-2 isolates, serovar 5-10 isolates, serovar 7-51 isolates, serovar 11-2 isolates and serovar 12-2 isolates . Of the remaining 140 isolates, 91 gave cross-reactions with serovars 3 and 6, one cross-reacted with serovars 9 and 10, one cross-reacted with serovars 9 and 11 whereas 47 gave no reaction with any of the antisera.

Prof Care Mother Child, 1995, 5(6), 168 - 70
Monitoring the uptake of Hib vaccine in Forth Valley; Davies M et al.; Haemophilus influenzae type b (Hib) infection is an important cause of morbidity and mortality among young children in this country . Immunisation against the disease using protein conjugate Hib vaccine was introduced in the United Kingdom on 1 October 1992 . To monitor the impact of this new vaccine in the routine childhood immunisation schedule in Forth Valley Health Board area, a survey of the parents of 200 children born during August 1992 was carried out . A total of 163 (82%) parents responded . While most parents had heard of Hib vaccine or of diseases caused by Hib, specific gaps in their knowledge were noted . In particular a substantial minority (31%) were not aware of the role of Hib vaccine in preventing meningitis . Among health professionals who advised parents on immunisation, the most important group identified by parents were health visitors, followed by family doctors . Leaflets produced by the Health Education Board for Scotland also formed an important and valuable source of information for parents, as did television, radio and newspapers . Monitoring the uptake of Hib vaccine in the sample of 200 children revealed a high uptake of the three recommended doses (96%), with only one child receiving no immunisations at all . If this level of uptake is achieved in other areas then the full potential of the new Hib vaccine in preventing infection among young children will be considerable.

Scand J Infect Dis, 1995, 27(4), 303 - 13
Characterization of Haemophilus influenzae isolates from the respiratory tract of patients with primary antibody deficiencies: evidence for persistent colonizations; Samuelson A et al.; A total of 117 consecutive patients with primary antibody deficiencies were followed for up to 5 years with regard to acute respiratory tract infections . Nontypeable Haemophilus influenzae (NTHI) was the sole pathogen in 61% (202/330) of the samples from which a potential pathogen was recovered . Common variable immunodeficiency (CVI) was the most prevalent condition (27/39 patients) in the group where H . influenzae was isolated . In patients where H . influenzae was not found only 9/78 patients had CVI . 49 of these 78 patients had isolated IgG3 or IgA deficiency . Both of these entities seemed to be associated with a lower prevalence of NTHI infections . 13 of 18 patients with at least 2 isolates of NTHI were colonized with the same strain from 3 to 43 months as shown by total genomic DNA-fingerprinting . Recurrent symptomatic infections occurred in these patients despite substitution therapy with gammaglobulins and repeated antibiotic treatments . All but 2 of the 224 H . influenzae isolates were beta-lactamase negative and sensitive to ampicillin . The use of 10 lipopolysaccharide-specific monoclonal antibodies in a whole cell ELISA showed that the LPS-epitopes on the 224 H . influenzae isolates from the hypogammaglobulinemic group were very similar to 499 NTHI isolates from immunocompetent patients with respiratory infections . One may therefore conclude that i) patients with CVI, were prone to be permanently colonized with NTHI, and ii) the colonizing bacteria were ordinary strains showing the same LPS-phenotypes as those strains that cause acute respiratory tract infections in immunocompetent individuals.

Scand J Infect Dis, 1995, 27(5), 537 - 9
Rapid diagnosis of bacterial meningitis by a seminested PCR strategy; Olcen P et al.; A polymerase chain reaction (PCR) based diagnostic assay has been developed for the simultaneous detection in cerebrospinal fluid (CSF) of Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus agalactiae, Listeria monocytogenes and bacteria in general . In the present communication we describe the design of primers for S . pneumoniae, S . agalactiae, and L . monocytogenes, and a general PCR protocol for the assay . The diagnostic outcome is presented for a small collection of CSF specimens including 2 samples from patients with culture-negative purulent meningitis.

Drugs, 1995, 49 Suppl 2, 144 - 51
The role of new quinolones in the treatment of respiratory tract infections; Finch RG; Infections of the respiratory tract are the leading cause of antibacterial prescribing in both hospital and community practice . The microbial aetiology is diverse in both of these settings and differs in the distribution and virulence of the pathogens . Furthermore, in recent years the antibacterial susceptibility of many of the common pathogens has changed significantly . In particular, penicillin resistance has emerged among pneumococci, while beta-lactamase production among Haemophilus influenzae and many Gram-negative bacilli has led to alterations in first-line therapy options . The fluoroquinolone antibacterials have been used in selected respiratory tract infections, but concerns have remained with regard to their efficacy in infections caused by marginally susceptible organisms, and in particular pneumococcal infections . The availability of a number of quinolones with enhanced Gram-positive activity, which includes Streptococcus pneumoniae, is of considerable interest . In vitro data and preliminary clinical experience with sparfloxacin suggest that managing pneumococcal lung disease with this and future agents is a distinct possibility . One caveat must be considered, and that is the potential for more resistant strains of pneumococci emerging, against which even these new quinolones could prove less effective.

Scand J Infect Dis, 1995, 27(3), 291 - 3
Haemophilus aphrophilus discitis and vertebral osteomyelitis; O'Driscoll JC et al.; An unusual case of discitis and vertebral osteomyelitis due to Haemophilus aphrophilus is described . Infections due to this organism have usually responded to treatment with beta-lactam antibiotics . However, our isolate was resistant to third-generation cephalosporins which has not been reported previously in the world literature . The patient made a good clinical response to ciprofloxacin treatment.

Scand J Infect Dis, 1995, 27(3), 229 - 34
Treatment of acute maxillary sinusitis--comparing cefpodoxime proxetil with amoxicillin; von Sydow C et al.; In order to evaluate the clinical efficacy and tolerance of cefpodoxime proxetil, compared with that of amoxicillin in the treatment of acute bacterial maxillary sinusitis, a randomized, double-blind, parallel group comparative study was performed . A total of 286 adults patients were included at 12 centres, each treatment group consisting of 143 patients . Each patient was treated for 10 days and observed before and after treatment . The observations included clinical, roentgenological, bacteriological and laboratory examinations . At inclusion, the most common pathogens were Haemophilus influenzae (24%) and Streptococcus pneumoniae (17%) . In the per protocol analysis, 117 patients in the cefpodoxime group and 113 in the amoxicillin group were evaluable for clinical efficacy . The clinical response rates were 96% and 91%, respectively . The corresponding figures in the intent-to-treat analysis were 130 and 128 patients, with clinical response rates of 93% and 88%, respectively . Cefpodoxime proxetil proved clinically as effective as amoxicillin in the treatment of acute bacterial maxillary sinusitis . It was more effective in eradicating H . influenzae and was more efficient in improving the radiological score . Adverse events were reported in 20% of cefpodoxime cases and in 16% of amoxicillin cases . There was no statistically significant difference between the groups.

Infection, 1995, 23 Suppl 2, S79 - 82
Acute otitis media in children: a study of nasopharyngeal carriage of potential pathogens and therapeutic efficacy of cefixime and amoxicillin-clavulanate; Boulesteix J et al.; We conducted a large, multicenter, randomized, open-label study throughout France comparing the efficacy and safety of cefixime suspension (8 mg/kg/day, b.i.d., for 10 days) versus amoxicillin-clavulanate suspension (80 mg/kg/day, t.i.d., for 10 days) in 510 children (ages 6 to 36 months) with acute otitis media . The most frequent microorganisms colonizing the nasopharynx at the start of treatment were Streptococcus pneumoniae (51.5%), Haemophilus influenzae (45%) and Moraxella catarrhalis (30.2%) . Rates of beta-lactamase positivity were 32.1% and 95.3% for H . influenzae and M . catarrhalis, respectively . Decreased susceptibility of S . pneumoniae to penicillin was found in 39.7% of isolates . Clinical efficacy was 87.8% (223/254) for cefixime and 87.0% (215/247) for amoxicillin-clavulanate . At the 5-week follow-up visit, relapse had occurred in 15.7% (31/197) of cefixime-treated patients and in 15.6% (32/205) of those treated with amoxicillin-clavulanate . We conclude that these two regimens are equally effective in acute otitis media in children.

Infection, 1995, 23 Suppl 2, S74 - 8
Rational use of oral antibiotics for pediatric infections; Sunakawa K et al.; We carried out a survey in Japan to investigate compliance among children given oral antibiotics in an outpatient setting . The results of our survey revealed that, in Japan, approximately one-quarter of patients did not take their full course of antibiotics . Reasons for unsupervised self-discontinuation included: (1) the parent or guardian judged the infection to be cured; (2) the child refused to take the drug; and (3) the appearance of side effects . Causative organisms often involved in respiratory infections experienced in out-patient medicine include pneumococci, streptococci, staphylococci, Haemophilus influenzae, Moraxella (Branhamella) catarrhalis and Mycoplasma pneumoniae . The beta-lactams are effective against all of these bacterial species, with the exception of M . pneumoniae . We conducted a survey of beta-lactam antibiotics currently on the Japanese market and compared them to other oral antibiotics used to treat respiratory infections . Ease of administration, based on the incidence of adverse effects, particularly diarrhea, the dosage form, taste, dosage per administration and the number of doses required per day, are reported.

Infection, 1995, 23 Suppl 2, S59 - 63; discussion S64
Antimicrobial agents for community-acquired respiratory tract infections; Barry AL; Chemotherapy of community-acquired respiratory tract infections was reviewed from a microbiological perspective . The current worldwide spread of penicillin-resistant Streptococcus pneumoniae and of ampicillin-resistant Haemophilus influenzae has required a reassessment of the antimicrobial agents being used for empiric therapy . In vitro data with different orally administered antibiotics were reviewed in order to identify any deficiencies in their spectra of activity against four common respiratory tract pathogens . Cefixime, cefuroxime axetil, cefprozil, amoxicillin-clavulanic acid and trimethoprim-sulfamethoxazole were active against all four species other than penicillin-resistant pneumococci.

Mem Inst Oswaldo Cruz, 1995 Jan-Feb, 90(1), 21 - 4
Development of a collection of bacteria causing meningitis in Rio de Janeiro from 1990 to 1991; de Filippis I et al.; From March 1990 to December 1992, the National Institute for Quality Control of Health-INCQS Research Collection received 1476 bacterial samples isolated from human cerebrospinal fluid of patients suspect of meningitis in Rio de Janeiro, from the Sao Sebastiao State Institute of Infectious Diseases (IEISS) . Neisseria meningitidis was found in most of these materials, followed in smaller number by Haemophilus sp . and Streptococcus pneumoniae . The great majority of N . meningitidis strains was serogroup B, followed by serogroup C and a few strains of serogroup W135 . More than 50% of the isolated bacterial agents came from the predominant 0-4 years age group . The majority of the strains were from patients in the region known as "Baixada Fluminense" (Low Lands) . The aim of the work presented here is to obtain samples of meningitis cases in at least 70% of the State of Rio de Janeiro and develop a collaborative research between INCQS-FIOCRUZ and the IEISS, in order to set up a collection of strains for future studies . However, despite work being carried out in a rather satisfactory way, difficulties still arise and have to be overcome, to survey data.

Chemotherapy, 1995 Jan-Feb, 41(1), 18 - 33
Antibiotic susceptibility tests with fastidious and nonfastidious bacterial reference strains: effects of aerobic versus hypercapnic incubation; Traub WH et al.; Representative antimicrobial drugs were examined under aerobic and hypercapnic (3 and 5% v/v CO2) incubation with the Bauer-Kirby agar disk diffusion, a broth microdilution method, and the agar dilution procedure against nonfastidious, standard ATCC quality control strains and against two beta-hemolytic streptococcal, two pneumococcal, and three Haemophilus influenzae ATCC strains . It was found that an atmosphere of 3-5% CO2 merely antagonized amikacin, gentamicin, and netilmicin; the activity of penicillin G was antagonized only against Staphylococcus aureus ATCC 29213 in broth media, but not against any of the other strains . The activity of teicoplanin, and less so that of vancomycin, was enhanced only against S . aureus strain ATCC 25923, but not against the other strains . It was concluded that susceptibility tests, excluding aminoglycoside antibiotics, of beta-hemolytic streptococci, pneumococci, and H . influenzae and H . parainfluenzae should be incubated under 3% (candle jar or incubator) or 5% CO2 (incubator) so as to ensure optimal growth of capnephilic strains and thus avoid potentially misleading large inhibition zones of deceptively low minimal inhibitory concentrations.

Nord Med, 1995, 110(2), 42 - 4, 54
{Multiresistant bacteria in a Scandinavian perspective}; Kristinsson KG; The global increase in multiresistant bacteria may herald the end of the antibiotic era . Recently, the most ominous sign has been the increasing resistance in pneumococci, enterococci and Staphylococcus aureus, as this has not been met with new effective antimicrobials . Resistant Haemophilus influenzae and meningococci are potential future problems . Except for the occurrence of multiresistant pneumococci in Iceland, hitherto the Nordic countries have largely escaped these problems, though multiresistant enterococci are being isolated with increasing frequency and penicillin-resistant pneumococci have become endemic in southern Sweden . Concerted action is needed in an attempt to halt the increasing resistance among important bacterial pathogens.

Laryngoscope, 1995 Jan, 105(1), 42 - 8
Qualitative and quantitative immunoglobulin production by specific bacteria in chronic tonsillar disease; Koch RJ et al.; Tonsillar tissue lymphocyte (TTL) function as measured by immunoglobulin production was assessed in vitro in 60 tonsils, 51 diseased and 9 normal controls . The diseased specimens were from children (aged 3 to 10 years) clinically classified as having recurrent tonsillitis (RT), idiopathic tonsillar hyperplasia (ITH), or recurrent tonsillitis with hyperplasia (RT/H) . TTLs were challenged with intact, heat-inactivated bacteria found in the core of diseased tonsils--Streptococcus pyogenes (SP) and Haemophilus influenzae type B (HIB) as well as the dominant bacterium (DB) grown from that particular tonsillar core . The phytomitogen, leukoagglutinin (LA), was used as a nonspecific activator . Qualitative immunoglobulin production was assessed for the immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) classes . Immunoglobulin-specific production was quantified at the basal level, and at 2, 4, and 6 days following stimulation . Stimulation with HIB produced the greatest amount of IgG and IgM in TTLs from control tonsils . The DB was a relatively weak stimulator of normal (control) TTLs, yet produced relatively brisk IgG responses in the RT and ITH categories . It did, however, yield only marginal IgM secretion in these groups . IgA was consistently produced after stimulation in diseased TTLs, yet was not elicited from normal TTLs . The aforementioned findings suggest a differential qualitative and quantitative immunoglobulin response for healthy, recurrently infected, and hyperplastic tonsils . Lymphocyte hypofunction along with structural changes associated with hyperplasia may be central to the etiology of chronic tonsillar disease . The tonsillar immunologic response in disease and health is discussed.

J Infect Dis, 1995 Jan, 171(1), 99 - 105
Transplacental antibody transfer following maternal immunization with polysaccharide and conjugate Haemophilus influenzae type b vaccines; Englund JA et al.; Passive transfer of antibody to infants born to women immunized during the third trimester of pregnancy with a Haemophilus influenzae type b (Hib) vaccine (PRP polysaccharide or Hib conjugates PRP-D or HbOC) was studied in 50 mothers and infants and 47 nonimmunized mother-infant pairs . Geometric mean total PRP antibody by RIA was 1.2 micrograms/mL at delivery in unimmunized women and 21, 149, and 171 micrograms/mL in women who received PRP, PRP-D, and HbOC, respectively . Mean cord PRP antibody levels were 0.29, 3.0, 17.5, and 29.3 micrograms/mL for the corresponding groups . Postimmunization and cord PRP antibody levels were higher after maternal immunization with conjugate vaccines than with PRP vaccine (P < .01) . PRP IgG1 subclass was transmitted more efficiently than IgG2 (56% vs . 35%, P < .01) . The proportion of anti-PRP IgG transmitted from immunized mothers to infants correlated with time between immunization and delivery . Administration of PRP conjugate vaccines to women during pregnancy resulted in higher levels of PRP antibodies in infants than did polysaccharide or no vaccine.

J Infect Dis, 1995 Jan, 171(1), 93 - 8
The impact of conjugate vaccine on carriage of Haemophilus influenzae type b; Barbour ML et al.; Conjugate vaccines against Haemophilus influenzae type b (Hib) may modify Hib pharyngeal colonization . Hib colonization was compared in 371 infants and their families . In Oxfordshire, infants received PRP-T (polyribosylribitol phosphate conjugated to tetanus toxoid) and in Buckinghamshire they did not (controls) . Infants were followed at 6, 9, and 12 months of age . Also, 6 unvaccinated Hib carriers were vaccinated and followed for 6 weeks . Hib acquisition was lower in vaccinees than controls (P < .01) . During surveillance, 1.5% of vaccinees and 6.3% of controls carried Hib (P = .04) . Among those with family Hib exposure, the carriage rates were 8.7% and 38.5% (P = .07), respectively . Hiv carriage rates were lower among vaccinees' unvaccinated siblings . Giving conjugate vaccine to a child carrying Hib did not rapidly terminate carriage . Thus, a primary means by which herd immunity to Hib is induced in a vaccinated population may be through reduction or delay in the initial acquisition of Hib.

J Infect Dis, 1995 Jan, 171(1), 209 - 12
Brazilian purpuric fever caused by Haemophilus influenzae biogroup aegyptius strains lacking the 3031 plasmid; Tondella ML et al.; Brazilian purpuric fever (BPF) is a life-threatening pediatric infection caused by Haemophilus influenzae biogroup aegyptius (Hae), an organism formerly associated with only self-limited purulent conjunctivitis . Strains of Hae causing BPF have a 24-MDa plasmid with a specific AccI restriction pattern designated 3031 . This plasmid was thought to code for a virulence factor because it had been detected only among Hae strains isolated from BPF cases or their contacts . From 3 typical BPF cases recently identified in Sao Paulo State, sterile-site Hae isolates were obtained; these isolates were similar to earlier BPF-associated Hae except they did not possess a 3031 plasmid . HindIII restricted chromosomal DNA from these strains was probed with purified 3031 plasmid DNA under high-stringency conditions . There was no evidence that 3031 plasmid DNA had become chromosomally integrated . It appears that the 3031 plasmid does not code for BPF-specific virulence factors.

J Infect Dis, 1995 Jan, 171(1), 161 - 9
Effect of interleukin-1 receptor antagonist and soluble tumor necrosis factor receptor in animal models of infection; Paris MM et al.; Intracisternal or intraarticular inoculation of rabbit recombinant interleukin (IL)-1 beta and rabbit tumor necrosis factor-alpha combined with IL-1 receptor antagonist (IL-1RA) and soluble tumor necrosis factor receptor (sTNFR), respectively, produced significantly less inflammation in rabbits than after inoculation of these cytokines alone . In contrast, when Haemophilus influenzae type b (Hib) or Hib lipooligosaccharide (LOS) was given intraarticularly with IL-1RA, sTNFR, or the combination, there was no significant or consistent modulation of synovial inflammation and cartilage proteoglycan degradation . In the experimental meningitis model, IL-1RA and sTNFR did not significantly reduce the meningeal inflammatory response associated with intracisternal inoculation of Hib LOS . These data indicate that specific cytokine inhibitors (sTNFR and IL-1RA) may not be effective in modulating inflammation induced by a broad inflammatory stimulus such as gram-negative bacteria or their products and suggest caution in using them to treat these infectious conditions in humans.

S Afr Med J, 1995 Jan, 85(1), 20 - 5
The costs and benefits of a vaccination programme for Haemophilus influenzae type B disease; Hussey GD et al.; Haemophilus influenzae type b (Hib) infection is a major cause of severe bacterial infection in young children in South Africa and world-wide . These diseases can be prevented by immunisation with conjugate Hib vaccines . In South Africa, unlike some developed countries, Hib vaccines are not part of the routine immunisation schedule . The objective of this study was to measure the expected net benefits from a hypothetical programme of vaccination of the 1992 Cape Town birth cohort (N = 46,537) . Costs were calculated by summing the estimated direct medical care costs together with the indirect costs of Hib disease . The latter were calculated by valuing human life using alternative, and conservative human capital and willingness-to-pay measures . The difference between Hib disease costs (i.e . the benefits which would be gained from a successful vaccination programme) and the costs of the vaccination programme itself (HibTITER, Praxis Biologicals) defined the expected net benefits . In the absence of an immunisation programme, the estimated economic costs of Hib disease in the 1992 Cape Town cohort ranged from R10.7 million to R11.8 million . The costs of introducing the vaccine would have amounted to R8.3 million . Had the vaccine been administered to the 1992 birth cohort, benefits would have exceeded costs by between R2.4 million and R3.5 million.

Scand J Infect Dis, 1995, 27(1), 63 - 7
Invasive Haemophilus influenzae disease: epidemiology and clinical spectrum before large-scale H . influenzae type b vaccination; Hugosson S et al.; In a prospective study between January 1987 and December 1992, 103 patients with invasive Haemophilus influenzae (Hi) infection were identified in a well-defined population before large-scale Haemophilus influenzae type b (Hib) vaccination was introduced . The incidence (case/100,000/year) of invasive Hi infection was 5.9 for the whole population, 55 for children 0-4 years old and as high as 2.8 for adults . Hib was the predominant cause of the infection (83 cases) in children but, in adults, 13/39 (30%) cases were caused by non-typable Hi and 6/39 (19%) by Hi serotype f . Three patients (3%) died and 6 (5.8%) suffered a permanent sequel from the infection . All patients with such a sequel had invasive Hib infection . No significant difference between patients 0-6 years old and matched controls regarding the frequency of subnormal serum levels of immunoglobulins was found.

Scand J Infect Dis, 1995, 27(1), 57 - 61
Antimicrobial resistance in Haemophilus influenzae isolated from blood, cerebrospinal fluid, middle ear fluid and throat samples of children . A nationwide study in Finland in 1988-1990; Nissinen A et al.; A nation-wide survey of the prevalence of antimicrobial resistance in Haemophilus influenzae was conducted on isolates collected in 1988-90 from middle ear fluid (MEF), blood, or cerebrospinal fluid (CSF) in infected children or throat samples of healthy children . Altogether 885 strains were examined regarding capsular type b, beta-lactamase production and the minimal inhibitory concentration (MIC) of ampicillin, cefaclor, erythromycin, tetracycline, chloramphenicol, trimethoprim and trimethoprim-sulfamethoxazole for these strains was determined by the agar dilution method . 99% (578/585) of MEF isolates, 93% (112/121) of throat isolates, but only 6% (10/179) of blood/CSF isolates were not of type b (Hib) . The rate of beta-lactamase production was 11.4% among Hib strains, 8.0% among non-type b MEF isolates, and 4.5% among non-type b throat isolates . No increase in the prevalence of beta-lactamase production in H . influenzae has taken place in Finland since the early 1980s . Resistance to ampicillin among strains that lacked beta-lactamase activity was rare (0.2%) . Of the non-type b MEF and throat isolates, 5.9% and 2.7%, respectively, were resistant to trimethoprim and 3.6% and 2.7%, respectively, to trimethoprim-sulfamethoxazole . Resistance to other drugs was rare (< 2%) in all isolate groups.

Microb Pathog, 1995 Jan, 18(1), 37 - 51
Serum bactericidal activity and phagocytosis in host defence against Haemophilus ducreyi; Lagergard T et al.; Serum bactericidal activity and phagocytic killing are two important mechanisms involved in the host defence against bacteria . Using some in vitro methods, serum bactericidal assay, phagocytic killing by polymorphonuclear leukocytes (PMN) and chemiluminescence, we have evaluated the significance of these mechanisms in the killing of Haemophilus ducreyi bacteria . Furthermore, induction of C3 conversion and deposition of immunoglobulins, C1q and C3, on the surface of bacteria was studied by crossed immunoelectrophoresis and ELISA, respectively . Transmission electron microscopy was employed to study internalization of bacteria by PMN . H . ducreyi and lipooligosaccharide preparations from these bacteria were able to induce conversion of complement factor C3 in normal human serum (NHS) . Exposure of bacteria to NHS resulted in deposition of IgG, IgM and complement factors C1q and C3 on the surface of bacteria . H . ducreyi bacteria lost their viability when incubated with fresh but not inactivated normal serum at high concentrations, indicating that the bacteria are sensitive to the complement-dependent bactericidal activity of serum . There were some variations between different strains regarding their susceptibility to the bactericidal activity of NHS, but for eight strains tested, all of the bacteria exposed were not killed in medium containing up to 70% of fresh serum . Complement-mediated opsonophagocytic killing of H . ducreyi by PMN was more effective than complement-dependent bactericidal activity of fresh normal sera . Bacteria treated with heat inactivated immune sera, on the other hand, were as sensitive to the bactericidal effect of PMN as those treated with non-inactivated immune sera, indicating the role of antibodies in opsonophagocytosis . H . ducreyi bacteria were also killed by PMN in the absence of serum antibodies and complement . Using the chemiluminescence assay, H . ducreyi was shown to activate PMN in the absence of serum as well as after opsonization with complement and antibodies . Our results therefore indicate that both opsonic- and non-opsonic mechanisms are involved in the phagocytosis and the subsequent killing of H . ducreyi bacteria . Although both complement and antibodies enhance the ability of phagocytes to kill H . ducreyi, neither component is sufficient for effective killing of H . ducreyi.

Pediatrics, 1995 Jan, 95(1), 21 - 8
Dexamethasone therapy for children with bacterial meningitis . Meningitis Study Group; Wald ER et al.; OBJECTIVE: To determine whether treatment with dexamethasone and ceftriaxone for children with bacterial meningitis reduces the frequency of either sensorineural hearing loss or other neurologic sequelae . DESIGN . This was a prospective, multicentered, placebo-controlled clinical trial . Subjects were followed for 1 year . SETTING . The study was conducted in six children's hospitals located in Pittsburgh, Houston, Los Angeles, Chicago, Washington, D.C., and Columbus, Ohio . PATIENTS . Enrolled were 173 children, 8 weeks to 12 years of age, with suspected bacterial meningitis; 143 children were evaluable . Eighty-seven percent of patients were followed for at least 6 weeks to 3 months, and 67% were followed for 1 year . INTERVENTIONS . Subjects were randomized to receive ceftriaxone with or without dexamethasone (0.15 mg/kg every 6 hours for 4 days) . Auditory brainstem responses (ABR) were measured within 24 hours of admission . MAIN OUTCOME MEASURES . Hearing, development, and neurologic sequelae were assessed at the time of discharge and 6 weeks and 1 year later . MAIN RESULTS . One hundred forty-three patients (69 received dexamethasone and 74 received placebo) with bacterial meningitis were evaluable: Haemophilus influenzae type b (83), Streptococcus pneumoniae (33), Neisseria meningitidis (24), and three others . Overall, there was no significant difference in auditory outcome between dexamethasone and placebo recipients . Twenty-two children had bilateral moderate or more severe hearing loss at the time of the first ABR . At follow-up, the resolution of hearing impairment was nearly identical for each group . Nine of ten children who remained persistently deaf were deaf at the time of the first ABR . There were no differences in neurologic or developmental outcome between groups . CONCLUSION . All but one child with persistent bilateral moderate or more severe hearing loss had demonstrable deafness at the time of the first ABR . Dexamethasone did not significantly improve audiologic, neurologic, or developmental outcome in children with bacterial meningitis.

J Antimicrob Chemother, 1995 Jan, 35(1), 85 - 93
Factors affecting the intracellular accumulation and activity of azithromycin; Pascual A et al.; Azithromycin is a new macrolide which accumulates in high concentrations in human phagocytes . The cellular to extracellular ratio (C/E) of azithromycin concentrations (fixed extracellular concentration 1 mg/L) in human polymorphonuclear leucocytes (PMN) were significantly affected by small increases in the environmental temperature (C/E 20.3 +/- 2 and 59.4 +/- 6 at 37 degrees C and 40 degrees C, respectively) . PMN-associated azithromycin was not affected by the presence of different concentrations of human serum . The intracellular accumulation of azithromycin decreased slightly (C/E approximately 5) when cells were activated with PMA or opsonized with zymosan . The phagocytosis of opsonized Staphylococcus aureus or Haemophilus influenzae, however, slightly increased the intracellular concentrations of azithromycin . At different extracellular concentrations, azithromycin did not affect the production of hydrogen peroxide and superoxide radicals by PMN . The intracellular survival of H . influenzae in human PMN was abolished in the presence of concentrations higher than 0.125 mg/L of azithromycin . Under the same experimental conditions, however, azithromycin did not show any intracellular activity against S . aureus.

Vaccine, 1995 Jan, 13(1), 104 - 8
Evaluation of booster doses of Haemophilus influenzae type b-tetanus toxoid conjugate vaccine in 18-month-old children; Scheifele DW et al.; A booster dose of Haemophilus influenzae type b conjugate vaccine in the second year of life is the final step in the recommended series of doses to protect infants from invasive infection . This study assessed the safety and immunogenicity of PRP-T conjugate vaccine booster doses (Act-HIB, Connaught Laboratories Ltd) . The participants were 367 healthy children who had taken part in a study of primary immunization with PRP-T . At 18-19 months old, subjects were randomly assigned to receive diphtheria-pertussis-tetanus (DPT) and PRP-T vaccines either mixed in one syringe (n = 183) or separately in opposite limbs (n = 184) . Adverse events were monitored for 48 h after immunization . Blood was obtained prior to vaccination in half of the subjects (combined injections group) and following vaccination in all subjects to test for antibodies to each of the antigens administered . Local adverse reactions were infrequent with PRP-T alone and equally frequent at sites of DPT or DPT/PRP-T injection, except for redness > or = 25 mm in diameter which was more frequent after the combined vaccines (25.1 versus 14.1%, p < 0.01) . Systemic adverse events did not differ in type or frequency between groups . Before immunization, the geometric mean anti-PRP level in those tested was 0.41 micrograms ml-1; 26.7% had levels below 0.15 micrograms ml-1 . Both treatment groups responded strongly to vaccination . In those serially tested, anti-PRP levels rose by over 90-fold, to 38.1 micrograms ml-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Wien Klin Wochenschr, 1995, 107(8), 256 - 7
{Haemophilus influenzae meningitis in Austria: 1990-1992 incidence}; Vutuc C et al.; The incidence of Haemophilus influenzae meningitis in children aged less than 5 years in Austria was 9.5/10(5) (n = 42) in the year 1990, 12.4/10(5) (n = 56) in 1991 and 10.4/10(5) (n = 48) in 1992 . In each of the other 5-year age groups the incidence was lower than 1/10(5) . In 1992 Hib vaccine was registered and recommended for children below 5 years of age . So far no impact of immunisation has been observed on the incidence of meningitis . A new strategy must be found to improve the implementation of immunisation.

Mol Microbiol, 1995 Jan, 15(1), 77 - 85
Evidence that surface fibrils expressed by Haemophilus influenzae type b promote attachment to human epithelial cells; Geme JW 3rd et al.; Haemophilus influenzae type b is a Gram-negative bacillus that initiates infection by colonizing the upper respiratory tract . Previous studies have established that H . influenzae haemagglutinating pili possess adhesive properties and influence the process of colonization . Additional studies suggest the presence of a second H . influenzae adhesin distinct from haemagglutinating pili . In the present study, we examined a non-piliated H . influenzae type b strain by transmission electron microscopy and visualized occasional short, thin, surface fibrils . Subsequently, we isolated a spontaneous mutant that lacked surface fibrils and was deficient in adherence to cultured human epithelial cells . Using a cloning strategy that exploited this mutant, we isolated a fragment of DNA that promotes in vitro adherence to human epithelial cells when expressed in laboratory strains of Escherichia coli . Mutagenesis of this fragment in a series of H . influenzae type b strains resulted in loss of expression of surface fibrils and a marked decrease in attachment . Furthermore, restoration of surface fibril expression was associated with reacquisition of wild-type levels of adherence . Our results are consistent with the conclusion that H . influenzae type b surface fibrils have adhesive capacity . We speculate that these organelles facilitate colonization of the human respiratory tract.

Mol Microbiol, 1995 Jan, 15(1), 107 - 18
Region II of the Haemophilus influenzae type be capsulation locus is involved in serotype-specific polysaccharide synthesis; Van Eldere J et al.; The central (serotype-specific) Region II of the Haemophilus influenzae Type b capsulation locus cap is 8.3 kb long and contains a cluster of four genes . We show that these genes, designated orf1 to orf4, are involved in the biosynthetic steps required for the formation of the Type b capsular polysaccharide and that orf1 probably encodes a CDP-ribitolpyrophosphorylase . We present evidence that growth of polysaccharide chains takes place through the alternating addition of single sugar nucleotides.

J Infect, 1995 Jan, 30(1), 67 - 9
Haemophilus paraphrophilus infection: a pitfall in laboratory diagnosis; Chadwick PR et al.; Many clinical laboratories have difficulty in identifying a group of organisms which are catalase negative, oxidase positive, Gram negative rods . We describe a case of purulent sacroiliitis due to Haemophilus paraphrophilus where the organism was initially misidentified as Eikenella corrodens leading to inappropriate antimicrobial chemotherapy . We review the strains of H . paraphrophilus and E . corrodens that were identified by the National Collection of Type Cultures over the last ten years . Only 21 of 100 strains identified as E . corrodens were submitted as E . corrodens . Seven strains submitted as possible E . corrodens were identified as H . paraphrophilus . Several different species of Gram negative rods may produce pitting on agar and this seems to be poorly recognised . However, further tests are available to facilitate correct identification of these strains.

Electrophoresis, 1995 Jan, 16(1), 135 - 48
Characterisation of Haemophilus influenzae proteins by two-dimensional gel electrophoresis; Cash P et al.; The proteins of nontypable and type b Haemophilus influenzae isolates were characterised using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) . Coomassie Brilliant . Blue R-250 was used for protein detection . Two hundred and twenty eight proteins were resolved from whole cell lysates prepared from a standard nontypable H . influenzae strain (designated HI-64443) when isoelectric focusing was used for the first-dimensional separation of 2-D PAGE . When nonequilibrium pH gel electrophoresis (NEPHGE) was used to separate basic proteins in the first dimension, 50 proteins were detected for HI-64443; 20 of the basic proteins detected were considered to be unique for this separation protocol . The apparent molecular weights and isoelectric points were determined for 82 of the proteins resolved for HI-64443 . The variation of the proteins from the standard bacterial strain (HI-64443) was determined for nontypable H . influenzae isolates . On the basis of their electrophoretic mobilities, 17.5% of the proteins of HI-64443 were shared by four other nontypable H . influenzae strains analysed . These data identified both conserved and variable proteins among the nontypable H . influenzae isolates analysed . The results obtained indicated that 2-D PAGE was able to discriminate nontypable H . influenzae into population clones identified by other procedures . The 2-D protein profiles obtained for type b H . influenzae strains were similar to those obtained for nontypable H . influenzae strains . The extent of the protein variation observed between type b and nontypable H . influenzae strain was similar to that observed among nontypable strains alone . These data are discussed in relation to the application of 2-D PAGE as a tool for studies on bacterial epidemiology and for the analysis of the genome structure and gene expression of Haemophilus influenzae.

Arch Pediatr, 1995 Jan, 2(1), 86 - 8
{Treatment of acute otitis media}; Francois M; The treatment of acute otitis media (AOM) has three main aims: to relieve pain, to control fever and in case of suppurative AOM, to overcome the bacterial infection . The two former aims are best managed with salicylates or paracetamol . The local instillation of drops of an anaesthetic-antiseptic solution in the external canal is a useful adjuvant in painful congestive viral otitis . Antibiotherapy is only indicated in suppurative AOM . The most common organisms being Haemophilus influenzae and Streptococcus pneumoniae, amoxicillin is the first line treatment . However, in children who were treated for suppurative AOM in the previous months, amoxicillin/clavulanic acid or a second generation cephalosporin is preferable . Erythromycin-sulfonamide may also be used, particularly in children who are allergic to beta-lactamines . In case of failure of the first choice antibiotic treatment, it is necessary to perform a bacteriological study of the effusion which will determine the appropriate antibiotic to be used in second hand . The duration of the antibiotic treatment must be of 8 days in the absence of spontaneous perforation, and of 10 days in case of perforation . An examination of the tympanum at 10 days is recommended in infants under 6 months of age and in children with repeated AOM . A myringostomy is only indicated when a bacteriological evaluation is needed, mainly in infants under 6 months of age, in immuno-compromised children, and in case of failure of a first line antibiotic treatment.

Arch Pediatr, 1995 Jan, 2(1), 29 - 33
{Bacteriological study of purulent otitis media in children in CHU in the tropical zone}; Cisse MF et al.; BACKGROUND--Haemophilus influenzae and S pneumoniae are the most common causative agents of acute otitis media in Europe and the USA . This work aimed to identify the agents in Senegal and to study their sensitivity to antibiotics . POPULATION AND METHODS--Two hundred and one patients, aged 0 to 15 years, with persistent middle-ear effusion, were included in this study from 1983 to 1993 . Purulent samples aspirated from the external canal were analysed for bacteriology and sensitivity testing . RESULTS--Eighty two percent of cultures were positive for Staphylococcus aureus (37%), Pseudomonas aeruginosa (25%), Proteus (18%) and Klebsiella (8%) . Positive cultures were found mainly in children aged between 1 and 5 years . Amikacin and cefotaxim were the most active antibiotics against the majority of strains . Staphylococcus aureus was always resistant to penicillin . CONCLUSIONS--Prevalence of Staphylococcus aureus as the causative agent of persistent middle-ear effusion may be explained by late examination . Its resistance to penicillin favors early administration of third generation cephalosporins or pristanimycin.

Acta Otorrinolaringol Esp, 1995 Jan-Feb, 46(1), 60 - 2
{Thrombophlebitis of the cavernous sinus secondary to polysinusitis . Report of a new case}; Garcia Del Castillo E et al.; Cavernous sinus thrombophlebitis syndrome is uncommon nowadays . Despite the wide range of antimicrobial agents it carries a high mortality . The disease frequently arises from infection of face, mouth, nose and paranasal sinuses, reaching the cavernous sinus by venous spread . Involvement of adjacent anatomic structures accounts for most of the clinical findings . Meningeal involvement, bilateral orbital edema and ocular cranial nerves palsy are very helpful in the differential diagnosis . Streptococcus spp., Staphylococcus spp., Haemophilus influenzae and anaerobic organisms are considered to be the most frequent etiological agents . In the present paper we report a case of cavernous sinus thrombophlebitis following left side polysinusitis . The patient presented with the main clinical features of the syndrome along with Streptococcus equisimilis and Fusobacterium necrophorum bacteremia . Urgent surgery of infected sinuses and appropriate antibiotic therapy led to a favorable outcome . The patient made and excellent progress and was discharged completely recovered two weeks after admission.

Acta Otorrinolaringol Esp, 1995 Jan-Feb, 46(1), 35 - 9
{Microbiological study of the nasopharynx}; Lacosta Nicolas JL et al.; A microbiological study of the posterior wall of the nasopharynx have been carried out in 90 children subjected to adenoidectomy by chronically hypertrophied and infected adenoids . Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes and Staphylococcus aureus are the most important pathogens responsible for upper respiratory tract infection . Adenoidectomy produces a physiological effect on the nasopharyngeal microflora by converting an abnormal flora into a nearly normal one . It has been found out that there is a relation between nasopharyngeal pathogens and the seasonal periods, showing a decrease in summer.

Can J Microbiol, 1995 Jan, 41(1), 70 - 4
Contact-dependent acquisition of transferrin-bound iron by two strains of Haemophilus parasuis; Charland N et al.; Two strains of Haemophilus parasuis, namely, the type strain (ATCC 19417) and strain E751, were investigated with respect to iron acquisition . Both strains produced iron-repressible outer membrane proteins and could acquire iron from porcine transferrin but not from porcine lactoferrin . Neither strain used bovine transferrin, and human transferrin was used to only a very limited extent, if at all . In all cases, iron acquisition from transferrin required direct contact between the organisms and the protein . An affinity isolation technique based on biotinylated porcine transferrin plus streptavidin-agarose, followed by SDS-PAGE, allowed the isolation and identification of two potential porcine transferrin binding polypeptides (94 and 60 kDa) from total membranes derived from the type strain grown under iron-restricted conditions but only one (96 kDa) from strain E751 . Each of these polypeptides was iron repressible and was not isolated when biotinylated human or bovine transferrin was used instead of biotinylated porcine transferrin . It is concluded that both strains acquire transferrin-bound iron by means of siderophore-independent mechanisms and that the isolated polypeptides represent porcine transferrin receptor components.

Clin Infect Dis, 1995 Jan, 20(1), 30 - 6
The reporting of communicable diseases: a controlled study of Neisseria meningitidis and Haemophilus influenzae infections; Standaert SM et al.; Surveillance systems for communicable diseases in the United States are primarily passive . We compared the passive reporting system for invasive disease caused by Neisseria meningitidis and Haemophilus influenzae with a concurrent, active laboratory-based system in the four metropolitan counties of Tennessee . The passive reporting system identified approximately 50% of all cases that were identified by the active system and accurately reflected trends in disease occurrence during the study period . Of all reported cases, physicians contributed fewer than 4% . Nearly 40% of all hospitals in the study area did not participate in the passive system . This lack of participation resulted in disproportionately increased reporting of disease among blacks . Inconsistencies in case definition within the state also contributed substantially to underreporting and lack of demographic representativeness of reported cases . The median reporting interval (the time from the onset of disease to transmission of the case report to the Centers for Disease Control and Prevention) was 24 days (range, 5-157 days) . Efforts to improve surveillance of those infections for which isolation of a pathogen is tantamount to a diagnosis should concentrate on laboratory-based reporting and the use of currently available computer telecommunication systems.

Arerugi, 1995 Jan, 44(1), 45 - 9
Effect of roxithromycin on respiratory bacterial infection in mice; Gonokami Y et al.; The effects of roxithromycin (RXM), an antibiotic of the macrolide family, on respiratory bacterial infection in mice were examined . BALB/c mice were administered with RXM orally at a dose of 5.0 or 2.5 mg/kg once per day for 14 days . On day 2 after the final drug administration, the mice were nasally infected with Haemophilus influenzae . RXM dose dependently inhibited the pathological changes in lung tissues induced by H . influenzae infection . RXM also enhanced 2',5'-oligoadenilate synthetase production in response to infection.

Jpn J Antibiot, 1995 Jan, 48(1), 92 - 102
{Fundamental and clinical studies of SY5555 in pediatrics}; Yokota T et al.; We assessed the in vitro antimicrobial activity and the clinical efficacy and safety of SY5555 in the field of pediatrics . The results obtained are summarized below . 1 . In vitro antibacterial activities of SY5555 against 52 clinical isolates were compared with those of clavulanic acid/amoxicillin (CVA/AMPC), cefotiam (CTM), cefpodoxime (CPDX), cefaclor (CCL) and cefdinir (CFDN) . Against Gram-positive bacteria, including Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes, SY5555 displayed antimicrobial activities superior or nearly equivalent to those of the reference agents used in the study . In cases of Gram-negative bacteria, the antimicrobial activity of SY5555 against Haemophilus influenzae was inferior to those of CPDX and CFDN . Against Klebsiella pneumoniae, the antimicrobial activity of SY5555 was less potent than that of CPDX . 2 . Forty-seven children with infectious diseases were treated with SY5555 dry syrup (powder dissolved just before use) . The clinical results were excellent in 24 and good in 16, with an efficacy rate of 85.1% . 3 . Bacteriological screening identified 30 pathogenic organisms, and the eradication rate was 76.7% . 4 . Side effects consisted of diarrhea in 12.5% (6 cases), loose stools in 4.2% (2 cases) and urticaria in 2.1% (1 case) of the patients . The only abnormal laboratory test value observed was an increase in eosinophil count in one child . 5 . The palatability of SY5555 dry syrup was very good; it was very easily ingestable or easily ingestable by 32 of the 48 children . From the above results, SY5555 dry syrup appears to be a useful drug with a preferable safety profile in the treatment of pediatric patients with infectious diseases.

Antimicrob Agents Chemother, 1995 Jan, 39(1), 238 - 40
In vitro activities of a streptogramin (RP59500), three macrolides, and an azalide against four respiratory tract pathogens; Barry AL et al.; Broth microdilution tests were carried out with 2,671 respiratory tract isolates from 19 medical centers throughout the continental United States . The tests compared a streptogramin (RP59500) to erythromycin, dirithromycin, clarithromycin, and azithromycin against Streptococcus pneumoniae, S . pyogenes, Haemophilus influenzae, and Moraxella catarrhalis . Against macrolide-susceptible strains, the potency of RP59500 was similar to that of the macrolides: the azalide, azithromycin, was two to four times more potent against H . influenzae . The azalide and three macrolides showed nearly complete cross-resistance . At 2.0 micrograms/ml or less, the streptogramin, RP59500, was active against both macrolide-resistant and -susceptible strains of S . pneumoniae (MIC for 50% of the strains tested, 0.25 microgram/ml; MIC for 90% of the strains tested, 0.5 microgram/ml).

Antimicrob Agents Chemother, 1995 Jan, 39(1), 221 - 6
Postantibiotic effects and postantibiotic sub-MIC effects of roxithromycin, clarithromycin, and azithromycin on respiratory tract pathogens; Odenholt-Tornqvist I et al.; Pharmacodynamic parameters have become increasingly important for the determination of the optimal dosing schedules of antibiotics . In this study, the postantibiotic effects (PAEs), the postantibiotic sub-MIC effects (PA SMEs), and the sub-MIC effects (SMEs) of roxithromycin, clarithromycin, and azithromycin on reference strains of Streptococcus pyogenes group A, Streptococcus pneumoniae, and Haemophilus influenzae were investigated . The PAE was induced by 2x MICs (S . pneumoniae) or 10x MICs of the different drugs for 2 h, and the antibiotics were eliminated by washing and dilution . The PA SMEs were studied by addition of 0.1, 0.2, and 0.3x MICs during the postantibiotic phase of the bacteria, and the SMEs were studied by exposition of the bacteria to the drugs at the sub-MICs only . Growth curves were followed by viable counts for 24 h . The SMEs were generally very short . A PAE of 2.9 to 8 h was noted for all antibiotics against all strains . Clarithromycin induced a statistically significantly shorter PAE on S . pneumoniae than did roxithromycin and azithromycin and did so also against H . influenzae in comparison with azithromycin . The PA SMEs were long and varied at 0.3x MIC between 6.4 19.6 h . This pronounced suppression of regrowth of bacteria which are first treated with a suprainhibitory concentration of antibiotics and then reexposed to sub-MIC levels indicates that long dosing intervals for macrolides and azalides can be allowed.

Przegl Epidemiol, 1995, 49(1-2), 23 - 8
{Haemophilus isolates in children suffering from chronic upper respiratory tract infections}; Chylak J et al.; For a three year period, between 1992 and 1994, 271 isolates of H . influenzae and H . parainfluenzae were examined using biochemical tests, beta-lactamase production and antibiotic susceptibility patterns . H . influenzae was examined by serological typing using polyvalent and monovalent sera a-f (Difco), as well . The strains were derived from children who were treated because of chronic pharyngitis . Sensitivity tests to Erythromycin, Gentamycin, Cefradine, Ampicillin, Doxycycline, Cefuroxime, Amoxicillin/Clavulanic Acid, Co-Trimoxazole, were performed with a standard disk-diffusion method . Biotyping was performed using API NH set (bioMerieux) and the ability to produce beta-lactamase was measured using iodometric method . Of 157 H . influenzae, 58 (36.9%) were typeable with H . influenzae antisera . The most common biotypes of these strains were I and II although biotypes III-VII were presented, as well . Of 114 H . parainfluenzae most of the strains showed the biotypes I and II . Its worth noting that 14% of H . influenzae and 15.8% of H . parainfluenzae strains were capable of beta-lactamase production . The strains of H . influenzae and H . parainfluenzae were most resistant to Cefradine and Co-Trimoxazole, respectively.

Med Trop (Mars), 1995, 55(1), 41 - 5
{Septic meningitis in children in Rwanda from 1983 to 1990 . Retrospective study at the Kigali Hospital Center}; Salaun-Saraux P et al.; To assess septic meningitis in pediatric units in terms of the bacteriologic distribution, mortality, and groups at risk, we conducted a retrospective study in the pediatric department of the Kigali Hospital Center (Rwanda) . Based on bacteriologic study of 1215 cerebrospinal fluid samples, there were 321 cases of septic meningitis due to identifiable germs and 68 involving cloudy fluid with no detectable germs, i.e . 1.5% of admissions to the Pediatric Unit of the Kigali Hospital Center . The most common organisms were pneumococcus (36.5%), Haemophilus influenzae (31%), salmonella (13%), and meningococcus (11.5%) . Most of the children (75%) presenting septic meningitis were under the age of 5 years . Overall mortality was 38% with rates of 52% and 39% for cases involving pneumococcus and salmonella respectively . The predominant clinical symptoms of pneumococcus meningitis were coma (p:0.000055) and respiratory compromise (p:0.02) . In contrast Haemophilus influenzae meningitis was associated with a lower incidence of coma (p:0.05) and malnutrition (p:0.017) . Salmonella meningitis was characterized by a higher incidence of fever over 38.9 degrees C (p:0.025) and malnutrition (p:0.01) . In patients with meningococcus meningitis, the incidence of convulsions appeared to be higher, at the threshold of statistical significance (p:0.052), whereas coma (p:0062) and respiratory distress (p:0.0024) were uncommon . Independently of etiology, no clinical symptom was associated with a statistically higher risk for death.

Pathology, 1995 Jan, 27(1), 74 - 8
Multi-centre collaborative study for the in vitro evaluation of new macrolides dirithromycin and erythromycylamine . Australian Group for Antimicrobial Resistance (AGAR); Fernandes CJ et al.; A national study was conducted to determine the in vitro activity of 2 newer macrolides, dirithromycin and erythromycylamine compared with that of erythromycin, tetracycline and penicillin . Nineteen major teaching hospitals participated in the study . Minimal Inhibitory Concentrations (MICs) were determined by agar dilution, mostly using Iso-Sensitest Agar and an inoculum of 10(4) cells per spot . 2284 clinically significant strains were isolated in late 1991 and early 1992, comprising 1736 Gram-positive cocci, 355 Haemophilus influenzae, 97 Moraxella catarrhalis, 32 Listeria monocytogenes, 25 Neisseria meningitidis and 39 Neisseria gonorrhoeae were tested . The study indicates that dirithromycin and erythromycylamine possess antibacterial activity equivalent to that of erythromycin against most Gram-positive cocci and M . catarrhalis . Strains resistant to erythromycin were also resistant to dirithromycin and to erythromycylamine . Tetracycline was as active as the macrolides against both penicillin-resistant and penicillin-susceptible strains of Staphylococcus aureus . Coagulase-negative penicillin-resistant staphylococci, compared with tetracycline, were relatively resistant to the macrolides . H . influenzae was less susceptible than the Gram-positive cocci.

Lung, 1995, 173(4), 233 - 41
Lymphocyte subsets in bronchoalveolar lavage after exposure to Actinobacillus pleuropneumoniae in pigs previously immunized orally or by aerosol; Pabst R et al.; Young pigs were immunized with the lung-pathogenic bacterium Actinobacillus (Haemophilus) pleuropneumoniae by aerosol or orally using viable and inactivated bacteria . The cellular changes in the bronchoalveolar lavage (BAL) were studied in repeated lavages after the pigs were infected with live bacteria . The nucleated cells in the BAL were differentiated and lymphocyte subsets determined . There were no major differences between the two routes of immunization or between viable and inactivated bacteria . The immunization induced an increase in all lymphocyte subsets studied and in the appearance of plasma cells and lymphoid blasts . The infection did not cause a further increase except in granulocytes . The lack of a booster-type increase in lymphocytes in the BAL might indicate a different immunologic reaction of the lung or that lymphocytes of the BAL do not represent lung lymphocytes in general . The protective effect of the immunization might be deduced from the increase in lymphocytes after immunization but not from the reaction pattern after infection.

Pharm Biotechnol, 1995, 6, 673 - 94
Haemophilus influenzae type b conjugate vaccines; Kniskern PJ et al.; In summary, all of the Hib conjugate vaccines are highly immunogenic and efficacious in children older than 12-15 months of age, and HbOC, PRP-OMPC, and PRP-T are highly immunogenic and demonstrated to be efficacious in infants as young as 2 months old . HbOC, PRP-OMPC, and PRP-T have been licensed in numerous countries for infants and are recommended for infant immunization . However, perhaps the greatest tribute one can pay to all four Hib vaccines described in this review is to note the dramatic decrease in the incidence of Hib disease that has occurred since their introduction . In fact, according to the Morbidity and Mortality Weekly Report (March 4, 1994), the incidence of Hib disease in children less than 5 years old has declined by 95% from 41 cases per 100,000 in 1987 to 2 cases per 100,000 in 1993, timing that coincides with the availability and use of the Hib conjugate vaccines (Anderson, 1994) . As universal administration is achieved and the apparent vaccine-induced reduction in carriage of Hib by the population continues, Hib vaccines may follow the lead of past vaccines (such as smallpox, measles, mumps, rubella, and polio) toward eradication of disease or at least a high degree of medical control, thereby virtually eliminating the mortality and insidious morbidity associated with invasive Hib diseases.

Bull Soc Sci Med Grand Duche Luxemb, 1995, 132(2), 17 - 20
{Type B Haemophilus influenzae infections . Experience at the Pediatric Hospital of Luxembourg}; De Jonghe M et al.; We have made a retrospective study of invasive Hib infections which have occurred in the Children's Hospital since 1980 to the end of July 1994; and we have been able to notice that since the introduction of vaccination against Hib, especially since it is free, the incidence of invasive Hib infections in the Grand Duchy of Luxembourg is in great decline.

Przegl Epidemiol, 1995, 49(3), 267 - 73
{The role of Haemophilus influenzae in epidemiology of respiratory infection and meningitis}; Grzybowska W et al.; Epidemiological situation of respiratory infection and meningitidis due to Haemophilus influenzae in Poland and in the world were described . We discussed carrier state of Haemophilus and risk factors for invasive H . influenzae disease.

Auris Nasus Larynx, 1995, 22(2), 80 - 5
Early inflammatory changes of the Haemophilus influenzae-induced experimental otitis media; Kawana M; Haemophilus influenzae is one of the most frequent pathogens of acute otitis media . To determine the middle ear response during the early stage of acute inflammation, a small amount of H . influenzae was inoculated into the bullae of guinea pigs through the tympanic membrane . The bullae were harvested at 6, 12, 24, 36, and 48 hours after H . influenzae inoculation and washed with phosphate-buffered saline (PBS) . The number of viable H . influenzae and inflammatory cells, the concentrations of myeloperoxidase (MPO) and lysozyme in the washing suspensions were measured, and compared with those in PBS-inoculated control ears . The number of viable H . influenzae increased very rapidly from 6 to 12 hours after inoculation and remained stationary up to 48 hours . The number of inflammatory cells and the MPO concentration were significantly higher in the H . influenzae-inoculated ears than in the control ears from 12 to 48 hours after inoculation . The lysozyme concentration was already significantly higher at 6 hours in the H . influenzae-inoculated ears; the lysozyme was released in the middle ear before the accumulation of inflammatory cells and degranulation of MPO from inflammatory cells . The results indicated that inflammatory reactions were present already at 6 hours after bacterial inoculation, and were rapidly accelerated during the subsequent hours . Consequently, acute middle ear inflammatory responses were seen immediately following inoculation of viable bacteria, and these responses originated in direct responses of middle ear mucosa, and oxidative and non-oxidative neutrophil metabolic products, which may cause tissue injury.

Auris Nasus Larynx, 1995, 22(2), 73 - 9
Effect of ibuprofen treatment during experimental acute otitis media; Diven WF et al.; In this study, the efficacy of concurrent treatment of experimental acute otitis media with ibuprofen and ampicillin was evaluated in chinchillas with respect to clearance of the effusion, presence of mucosal inflammation, and modulation of biochemical markers . Forty chinchillas were infected with non-typable Haemophilus influenzae and randomly assigned to treatment with either IM ampicillin (control) or ampicillin plus ibuprofen beginning on day 2 post inoculation . On days 5 and 10, animals from each group were killed, effusions recovered for biochemical assay, and the middle ears prepared for histological study . Differences in outcome measures favoring the control group were observed at the 5 day endpoint . However, at the 10 day endpoint, mucosal thickness was significantly less, the number of effusion free ears greater, and the concentrations of free fatty acids and thromboxane less in the animals treated with the combined therapy when compared to the control group . These results suggest that the addition of ibuprofen to ampicillin for the treatment of acute otitis media alters disease pathogenesis in this infectious model.

An Otorrinolaringol Ibero Am, 1995, 22(5), 439 - 48
{The microbiology of secretory otitis}; Lacosta JL et al.; The AA . realize a comparative study on the differences between the nasopharyngeal microbial flora of 50 children suffering a secretory otitis and other 40 children without middle ear disease . In nasopharyngeal cultures the pathogenic flora (Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Streptococcus beta hemoliticus group A, Staphilococcus aureus) amounted for 96 percent in children with secretory otitis, which figure was reduced to 80 percent in healthy infants (p < 0.05) . Haemophilus influenzae was the most identified microorganism in a both nasopharyngeal and otic flora . We have found a significative association (p < 0.001) among nasopharyngeal and otic flora of each individual.

Rev Mal Respir, 1995, 12(4), 371 - 6
{Diagnostic and therapeutic strategies in exacerbations of chronic bronchitis in city practice}; Taytard A et al.; The consensus conference convened by the French Language Society for Infectious Disease at Lille in 1991 stressed the fact that two germs were most often the cause of exacerbation in chronic bronchitis (Streptococcus pneumoniae and Haemophilus influenzae) and that antibiotic therapy was the "safe solution" and that the first intention treatment should be either penicillin A, a first generation cephalosporin or a macrolide for the first 8-10 days . A chest x-ray was recommended if there was the slightest doubt about co-existing parenchymal disease with a reevaluation around the 7th day and a prescription of penicillin A plus a beta-lactamase inhibitor or a second or third generation cephalosporin in case of failure . The aim of this study was to assess the diagnostic and therapeutic attitudes of general practitioners when faced with exacerbation in chronic bronchitis in an adult of 60 without severe signs and to find out the antibiotic of first choice and also the antibiotic to be used if the first treatment failed . One hundred doctors were drawn at random from a list of general practitioners in Bordeaux . They were requested to reply to a questionnaire on the strategy of first choice antibiotic and the means of reassessment of the treatment after it had been instituted and the strategy used when faced with a patient who did not improve after the initial treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

J Immunol Methods, 1994 Dec 28, 177(1-2), 89 - 99
Characterization of a monoclonal antibody to the capsule of Haemophilus influenzae type b, generated by in vitro immunization; Bunse R et al.; Monoclonal antibodies to polyribosylribitolphosphate (PRP), the capsular polysaccharide of Haemophilus influenzae type b (Hib), are useful tools in the investigation of the molecular and cellular mechanisms causing Hib meningitis . A better understanding of these mechanisms may lead to improved therapeutic strategies . A number of different in vivo immunization techniques in BALB/c mice were used, which did not however reveal detectable serum levels of antibodies to PRP . Therefore a modified in vitro immunization technique, originally established for in vitro immunization of human B lymphocytes, was used for this weak immunogen in mice . After 5 days of in vitro stimulation with purified PRP the splenic lymphocytes of BALB/c mice were fused with the mouse myeloma line P3-X63-Ag8.653 . One hybridoma produced an IgM antibody (12E7) which recognized the capsular polysaccharide in ELISA and specifically labelled all tested Hib strains in immune fluorescent microscopy . The blotted polysaccharide PRP was immunostained with monoclonal antibody 12E7 . Preincubation of Hib with this antibody enhanced the oxygen radical metabolism of polymorphnuclear leucocytes in a chemiluminescence assay . There was no cross-reactivity with the supernatants of other Haemophilus influenzae serotypes and other bacterial species, as shown by counterimmunoelectrophoresis.

Ugeskr Laeger, 1994 Dec 12, 156(50), 7497 - 503
{The childhood vaccination program . Background, status and future}; Plesner AM et al.; Surveillance of the Danish childhood immunization programme has taken place at Statens Seruminstitut since 1980 . A description of the prevalence of the diseases, which are included in the programme, is presented . The Danish childhood immunization programme has for many years been one of the best in the world although it differs markedly from other countries . The polio immunization programme with inactivated polio vaccine given first and then later live attennuated vaccine is probably the optimal polio immunization programme . The childhood immunization programme began in 1943 with free diphtheria vaccination, and tetanus immunization was added in 1949 . There was a big polio epidemic in 1952/53 and the polio vaccine was introduced in 1955 . All three vaccines have markedly reduced the prevalence of these diseases . Pertussis vaccine was introduced in 1961 and measles, mumps and rubella vaccination in 1987 . Vaccination against Haemophilus Influenzae type b was introduced with success in 1993 . In the future several changes will probably be made in the programme because of the possibility using new combined vaccines.

Gene, 1994 Dec 2, 150(1), 75 - 80
Cloning, analysis and expression of the HindIII R-M-encoding genes; Nwankwo DO et al.; The genes encoding the HindIII restriction endonuclease (R.HindIII ENase) and methyltransferase (M.HindIII MTase) from Haemophilus influenzae Rd were cloned and expressed in Escherichia coli and their nucleotide (nt) sequences were determined . The genes are transcribed in the same orientation, with the ENase-encoding gene (hindIIIR) preceding the MTase-encoding gene (hindIIIM) . The two genes overlap by several nt . The ENase is predicted to be 300 amino acids (aa) in length (34,950 Da); the MTase is predicted to be 309 aa (35,550 Da) . The HindIII ENase and MTase activities increased approx . 20-fold when the genes were brought under the control of an inducible lambda pL promoter . Highly purified HindIII ENase and MTase proteins were prepared and their N-terminal aa sequences determined . In H . influenzae Rd, the HindIII R-M genes are located between the holC and valS genes; they are not closely linked to the HindII R-M genes.

Gene, 1994 Dec 2, 150(1), 141 - 4
Construction of an ori cassette for adapting shuttle vectors for use in Haemophilus influenzae; Heidecker GJ et al.; An ori (origin of DNA replication) cassette, pORC, containing the P15a ori and the kanamycin-resistance-encoding gene from Tn5, was constructed . The cassette was used to convert an Escherichia coli promoter selection vector, which gene from Tn5, was constructed . The cassette was used to convert an Escherichia coli promoter selection vector, which contains a promoterless chloramphenicol (Cm) acetyltransferase-encoding gene (cat) downstream from a multiple cloning site (MCS) {Brosius and Lupski, Methods Enzymol . 153 (1987) 54-68}, to an E . coli-Haemophilus influenzae shuttle vector . The shuttle vector, pQL1, was shown to transform E . coli and H . influenzae efficiently . H . influenzae promoters were cloned into pQL1 by ligation of Sau3A-digested H . influenzae chromosomal fragments . Selection and semiquantitative analysis of promoter strength were performed on agar plates containing different concentrations of Cm . With the use of pQL1, H . influenzae gene regulation can now be studied in either H . influenzae or E . coli . In addition, elements of pORC can be used to convert other specialized E . coli vectors to E . coli-H . influenzae shuttle vectors.

J Infect Dis, 1994 Dec, 170(6), 1532 - 8
Peptidoglycan isolated from nontypeable Haemophilus influenzae induces experimental otitis media in the chinchilla; Leake ER et al.; Bacterial cell wall components induce a number of biologic effects and promote inflammatory changes in a variety of hosts . Peptidoglycan isolated from Streptococcus pneumoniae can induce inflammation in the middle ear; however, an analogous role for peptidoglycan derived from gram-negative otitis media pathogens has not been described . Peptidoglycan isolated from nontypeable Haemophilus influenzae (NTHi), a major cause of otitis media, was evaluated in a chinchilla model . The direct injection of the middle ear with 3-300 micrograms of peptidoglycan resulted in tympanic membrane inflammation, abnormal pressure in the middle ear, leukocytosis, and histopathologic changes in the middle ear mucosa that included marked edema, osteoneogenesis, focal hemorrhage, and a mononuclear infiltration into the subepithelial space . These data indicate that NTHi peptidoglycan induced inflammation and histopathologic changes in the tympanic membrane and middle ear mucosal epithelium and may contribute to the pathogenesis of otitis media.

J Exp Med, 1994 Dec 1, 180(6), 2181 - 90
Genetic locus for the biosynthesis of the variable portion of Neisseria gonorrhoeae lipooligosaccharide; Gotschlich EC; A locus involved in the biosynthesis of gonococcal lipooligosaccharide (LOS) has been cloned from gonococcal strain F62 . The locus contains five open reading frames . The first and second reading frames are homologous, but not identical, to the fourth and fifth reading frames, respectively . Interposed is an additional reading frame which has distant homology to the Escherichia coli rfaI and rfaI genes, both glucosyl transferases involved in lipopolysaccharide core biosynthesis . The second and fifth reading frames show strong homology to the lex-1 or lic2A gene of Haemophilus influenzae, but do not contain the CAAT repeats found in this gene . Deletions of each of these five genes, of combinations of genes, and of the entire locus were constructed and introduced into parental gonococcal strain F62 by transformation . The LOS phenotypes were then analyzed by SDS-PAGE and reactivity with monoclonal antibodies . Analysis of the gonococcal mutants indicates that four of these genes are the glycosyl transferases that add GalNAc beta 1-->3Gal beta 1-->4GlcNAc beta 1-->3 Gal beta 1--4 to the substrate Glc beta 1-->4Hep--R of the inner core region . The gene with homology to E . coli rfaI/rfaI is involved with the addition of the alpha-linked galactose residue in the biosynthesis of the alternative LOS structure Gal alpha 1-->4Gal beta 1-->4Glc beta 1-->4Hep-->R . Since these genes encode LOS glycosyl transferases they have been named lgtA, lgtB, lgtC, lgtD, and lgtE . The DNA sequence analysis revealed that lgtA, lgtC, and lgtD contained poly-G tracts, which, in strain F62 were, respectively, 17, 10, and 11 bp . Thus, three of the LOS biosynthetic enzymes are potentially susceptible to premature termination by reading frame changes . It is likely that these structural features are responsible for the high-frequency genetic variation of gonococcal LOS.

Infect Immun, 1994 Dec, 62(12), 5652 - 8
Conservation of immune responses to proteins isolated by preparative polyacrylamide gel electrophoresis from the outer membrane of nontypeable Haemophilus influenzae; Kyd JM et al.; Outer membrane proteins P2, P4, and P6 and two with molecular masses of 26 and 28 kDa have been purified from a strain of nontypeable Haemophilus influenzae by a preparative form of polyacrylamide gel electrophoresis (PAGE) . Outer membrane protein P6, with a molecular mass of 16 kDa (determined by sodium dodecyl sulfate {SDS}-PAGE) was purified by both native PAGE and SDS-PAGE from three strains of nontypeable H . influenzae and one strain of type b H . influenzae . The same conditions were required for purification from each strain . The suitability of proteins isolated by these methods was assessed by studying the immune response of rats immunized with P6 in incomplete Freund's adjuvant into the Peyer's patches . P6 purified by either native PAGE or SDS-PAGE did not differ significantly from P6 purified by gel filtration and anion-exchange chromatography in the ability to enhance pulmonary clearance of live bacteria . This study also investigated the effects of SDS on P2 immunological responses in vivo and the effects of the reagents Zwittergent and sodium lauryl sarcosinate on outer membrane protein lymphocyte-proliferative responses in vitro . It was found that the presence of SDS in the immunization emulsion enhanced the antigen-specific cell-mediated response but suppressed the antigen-specific antibody responses . The presence of residual traces of Zwittergent in an outer membrane protein preparation inhibited antigen-specific cell-mediated proliferation, whereas extraction of outer membrane proteins with sodium lauryl sarcosinate did not inhibit antigen-specific proliferation . These results demonstrate that preparative PAGE is a suitable method for the purification of proteins from the outer membrane of H . influenzae required for investigation of their immunological significance as vaccine candidates and that traces of reagents used during protein purification may play an important role in determining the success of in vivo and in vitro studies.

Infect Immun, 1994 Dec, 62(12), 5632 - 40
Haemophilus ducreyi attaches to and invades human epithelial cells in vitro; Totten PA et al.; Haemophilus ducreyi is a sexually transmitted pathogen that causes genital ulcers and inguinal adenopathy . Because chancroidal ulcers are most commonly located on the foreskins of uncircumcised males, we utilized human foreskin epithelial cells (HFECs) to investigate the initial interaction of H . ducreyi with its host . The eight different strains of H . ducreyi that were studied varied in their abilities to attach to these epithelial cells, with six strains consistently attaching to > or = 90% of HFECs and two strains attaching to < 25% of HFECs . The strains with low levels of adherence also failed to exhibit chaining in broth culture and were avirulent in the rabbit model, suggesting that virulence in this model and attachment may be linked . The most adherent strain, LA228R, was further evaluated for its ability to invade HFECs and HEp-2 cells . Scanning electron microscopy and transmission electron microscopy of HFECs after interaction with LA228R produced images consistent with attachment, ingestion into vesicles, and escape from the vesicles into the cytoplasm . In addition, the gentamicin protection assay and inhibition of invasion by cytochalasin B and D indicated that LA228R was able to invade both HFECs and HEp-2 cells . Further examination of the mechanisms involved in the adherence and invasion of H . ducreyi into epithelial cells and their correlation with virulence will provide a better understanding of the pathogenesis of the disease caused by this important pathogen.

Am J Respir Crit Care Med, 1994 Dec, 150(6 Pt 2), S118 - 22
The role of bacterial proteases in the pathogenesis of cystic fibrosis; Suter S; Among the roles of mediators damaging the respiratory epithelium in patients with cystic fibrosis (CF) during the course of chronic, purulent bronchitis, that of neutrophil proteases is well established . The role of bacterial proteases is less well known . Among all pathogens colonizing the airways in CF, Pseudomonas aeruginosa is quantitatively the dominant pathogen; Staphylococcus aureus and Haemophilus influenzae are present in lower numbers . Anaerobic bacteria may be detected in numbers exceeding those of Staphylococcus aureus and Haemophilus influenzae . Among all enzymes secreted by these bacterial strains, Pseudomonas elastase and alkaline protease were shown to be secreted in vivo over prolonged periods in the airways . These enzymes, mainly elastase, have proteolytic activity on many proteins involved in host defense mechanisms, often the same as those hydrolyzed by neutrophil proteases . Pseudomonas elastase has damaging effects on the respiratory epithelium; it has recently also been shown to augment the permeability of the respiratory epithelium cultured in vitro by proteolytic attack of tight junctions . The potential role of proteases and other enzymes secreted by anaerobic bacteria has not been studied in this disease . In conclusion, bacterial proteases secreted in vivo may play a role in the pathogenesis of the airway disease in CF; their relative importance to the role of host proteases is, however, often difficult to determine.

Pediatr Infect Dis J, 1994 Dec, 13(12), 1122 - 5
Opsonic activity of commercially available standard intravenous immunoglobulin preparations; Weisman LE et al.; Several standard intravenous immunoglobulin G (IVIG) products are available in the United States and have been used with the intent to treat or prevent infections in neonates . We evaluated more than 100 lots of IVIG, from 6 products, to determine the amount of opsonic antibody against neonatal pathogens . Neutrophil-mediated opsonophagocytosis was used to determine opsonic activity in these preparations for Staphylococcus epidermidis; Haemophilus influenzae type b; Streptococcus pneumoniae serotypes 3, 14 and 19; Group B Streptococcus serotypes Ia, Ib, Ia/c, II and III; and Escherichia coli (K1) . Pathogen-specific opsonic activity of the lots tested ranged from undetectable to 1:80 and was detectable in < 10% to > 90% of lots tested depending on the organism and manufacturer . Within an IVIG lot there was variable opsonic activity against different strains or serotypes of the same organism . Opsonic activity was significantly (P < or = 0.05) affected by the manufacturer's donor pool and less so by the manufacturing method . We conclude that the pathogen-specific opsonic antibody activity of an IVIG lot is: (1) highly variable for several common neonatal pathogens; (2) predominantly dependent on the donor pool and not the manufacturing method . Clinicians may more appropriately select therapy if the pathogen-specific antibody content of IVIG products by lot are known . In the future neonatal IVIG research should focus on using preparations with known pathogen-specific antibody activity.

Jpn J Antibiot, 1994 Dec, 47(12), 1753 - 61
{Antibacterial activities of cefetamet against clinically isolated strains from community acquired respiratory tract infections (II)}; Deguchi K et al.; Antibacterial activities of cefetamet (CEMT) against clinically isolated strains from patients with community acquired respiratory tract infections were compared to those of other oral beta-lactam antibiotics in the period from January to March 1994 . The following results were obtained . 1 . CEMT showed strong antibacterial activities against three major pathogens causing community acquired respiratory tract infections, Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae . However, antibacterial activities of CEMT against benzylpenicillin (PCG)-insensitive S . pneumoniae (PISP) and PCG-resistant S . pneumoniae (PRSP) were slightly weaker than of those of some the reference antibiotics . 2 . No MIC value changes of CEMT were observed from year to year against Moraxella subgenus Branhamella catarrhalis and Klebsiella pneumoniae.

Jpn J Antibiot, 1994 Dec, 47(12), 1728 - 52
{Bacteriological, pharmacokinetic and clinical studies on biapenem (L-627) in the pediatric field}; Motohiro T et al.; Antibacterial activities were determined and pharmacokinetics and a clinical studies were performed on biapenem (L-627), a novel parenteral carbapenem antibiotic, in infections in children . The following results were obtained: 1 . MICs of L-627 against clinical isolates were as follows: Among Gram-positive bacteria, MICs were 0.78 microgram/ml to > 100 micrograms/ml against 3 strains of methicillin-resistant Staphylococcus aureus (MRSA), and 0.10 microgram/ml to 0.39 microgram/ml against 8 strains of methicillin-sensitive S . aureus (MSSA), MICs against 5 of them were similar to those of imipenem (IPM), and MICs against 3 of them were slightly higher than those of IPM . MICs were < or = 0.025 microgram/ml to 0.39 microgram/ml against 7 strains of Streptococcus pneumoniae, and were similar to those of IPM, and lower than those of ceftazidime (CAZ) and piperacillin (PIPC) . Among Gram-negative bacteria, MICs were 0.78 microgram/ml and 3.13 micrograms/ml against 2 strains of Haemophilus influenzae, and were similar to those of IPM . 2 . Maximum plasma concentrations determined by the bioassay method after intravenous infusion of L-627 over 30 minutes at doses of 6.0 and 12.0 mg/kg, respectively, in 2 different pairs of 2 children each (total 4 cases) were observed upon completion of the treatment . Maximum concentrations at a dose of 6.0 mg/kg were 28.8 micrograms/ml and 24.6 micrograms/ml, and at a dose of 12.0 mg/kg were 65.4 micrograms/ml and 39.6 micrograms/ml, exhibiting a dose response . Plasma half lives in the beta phase were 0.97 and 1.20 hours at 6.0 mg/kg, and 0.72 and 0.94 hour at 12.0 mg/kg . Plasma concentrations determined by the HPLC method were lower than those determined by the bioassay . 3 . Urinary excretion rates in the first 5.5 hours after the 6.0 mg/kg dose were 81.4 and 75.3%, and after the 12.0 mg/kg dose were 91.0 and 73.8%, and these values were higher than those obtained using HPLC . 4 . Concentrations of L-627 in cerebrospinal fluid were determined in 2 cases of purulent meningitis . In one case, 30.3 mg/kg of L-627 was infused intravenously over 30 minutes and concentrations on days 1, 3, 7 and 14 observed at 60, 60, 45 and 45 minutes after respective dosages were 7.60, 1.30, 1.42 and 0.38 microgram/ml . Cerebrospinal fluid-plasma concentration ratio was determined on days 7 and 14 to be 5.5 and 1.2% respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Kansenshogaku Zasshi, 1994 Dec, 68(12), 1472 - 8
{A clinical study of respiratory infections due to mucoid Pseudomonas aeruginosa diagnosed by transtracheal aspiration}; Maeda K et al.; We performed a clinical study of 20 cases (33 episodes) of respiratory infections due to mucoid Pseudomonas aeruginosa by transtracheal aspiration (TTA) in the recent 10 years . There was only one pneumonia without underlying chronic lower respiratory infection (CLRTI) case positive for mucoid P . aeruginosa and others were all CLRTI among 33 TTA trials . In contrast, nonmucoid P . aeruginosa was recovered from 9 cases of respiratory infections without underlying CLRTI among 46 TTA trials . Monomicrobial infection of mucoid P . aeruginosa was 69.7%, and polymicrobial infection containing mucoid P . aeruginosa was 30.3%, and Haemophilus influenzae was the most frequent microorganism recovered with mucoid P . aeruginosa . The recovery rate of mucoid P . aeruginosa among P . aeruginosa-colonized cases was 56.3% in diffuse panbronchiolitis, and that was 42.9% and 40.0% in bronchiectasis and chronic bronchitis, respectively . Mortality due to pneumonia with nonmucoid P . aeruginosa was 46.1%, but there was no fatal pneumonia case with mucoid P . aeruginosa . In CLRTI, laboratory data were not remarkably different between mucoid and non-mocoid P . aeruginosa-colonized cases . Thus, these results suggest that mucoid P . aeruginosa is a more important organism in persistent infections in the lower respiratory tract compared with nonmucoid P . aeruginosa, and further investigations is required on the mechanism and clinical role of this infection.

J Clin Pathol, 1994 Dec, 47(12), 1116 - 7
Blood stained cerebrospinal fluid responsible for false positive reactions of latex particle agglutination tests; Camargos PA et al.; The accuracy of the latex particle agglutination test (LPAT) was assessed in blood stained cerebrospinal fluid (CSF) specimens from 166 paediatric patients, aged from three months to 13 years . A commercial LPAT kit was used to detect Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis A, B, and C soluble antigens . Culture of CSF specimens was used as the standard and all laboratory procedures were performed blind . The mean CSF erythrocyte count was 66,406 cells/mm3 in the cases and 11,560 cells/mm3 in the controls . The sensitivity and the specificity of LPAT were 83.8 and 94.0%, respectively, suggesting that LPAT is a useful diagnostic tool even in blood stained CSF specimens.

Immunology, 1994 Dec, 83(4), 624 - 30
Role of neutrophil Fc gamma RIIa (CD32) and Fc gamma RIIIb (CD16) polymorphic forms in phagocytosis of human IgG1- and IgG3-opsonized bacteria and erythrocytes; Bredius RG et al.; The four subclasses of IgG have different biological activities associated with their Fc regions . Fc gamma receptors on leucocytes (Fc gamma R) mediate binding and phagocytosis of opsonized particles . Two structurally and functionally distinct allelic polymorphisms of the Fc gamma R have been defined: the H/R131 forms of Fc gamma RIIa (CD32), and the neutrophil antigen 1 (NA1)/NA2 forms of Fc gamma RIIIb (CD16) . In this study the activities of allotypes of CD16 are analysed with antibacterial IgG subclass antibodies and with IgG1 and IgG3 anti-Rhesus D, and the activities of CD32 with IgG1 and IgG3 anti-Rhesus D . With respect to the allotypes of CD16, polymorphonuclear leucocytes (PMN) homozygous for Fc gamma RIIb-NA2 exhibited a lower (21-25%) IgG1-mediated phagocytosis of Staphylococcus aureus strain Wood (STAW), Haemophilus influenzae type b (Hib), and Neisseria meningitidis group B (NMen) than IIIb-NA1 PMN . The difference was apparent only when the micro-organisms were opsonized in the absence of complement, and was furthermore enhanced (34-52%) upon blockade of Fc gamma RIIa . In addition, monoclonal IgG3 anti-D-mediated rosette formation and phagocytosis was consistently found to be lower (16%) with Fc gamma RIIIb-NA2 than with IIIb-NA1 PMN . For the allotypes of CD32 we now show that IgG3 anti-D sensitized erythrocytes formed more (50%) rosettes and were phagocytosed at a higher rate with PMN carrying Fc gamma RIIa-H131 than with PMN carrying IIa-R131 . Heterozygous Fc gamma RIIa-H/R131 PMN exhibited intermediate phagocytic activity in this respect . This study illustrates a critical role of Fc gamma R allotypes in functional interactions with biologically relevant IgG subclass antibodies.

Rev Prat, 1994 Dec 1, 44(19), 2581 - 6
{Septic arthritis in children}; Glorion C; Septic arthritis is a synovial infection of bacterial origin . Such a diagnosis, suggested by pain and diminished resistance to infection, should be confirmed by puncture of the joint effusion . The condition calls for emergency hospitalisation and treatment in a surgical unit . Treatment should include draining and cleaning of the joint, immobilization at least in the early stages, and double parenteral antibiotic administration . Clinical, radiological and laboratory follow-up (CRP and ESR) should be pursued . Detection of the responsible germ is often difficult and requires great care in sampling and analysis . The frequency of Haemophilus in children under 4 years of age requires adaptation of antibiotic therapy . In newborns, diagnosis is often difficult and delayed, explaining the frequency of sequelae in this age group . The only important prognostic factor is the interval before beginning treatment.

Prim Care, 1994 Dec, 21(4), 693 - 715
Childhood immunization guidelines: current and future; Zimmerman RK et al.; Recent additions to the immunization schedule include acellular pertussis vaccine, and hepatitis B vaccine for all infants and selected adolescents . The third dose of OPV is recommended at 6 months of age and the first dose of MMR vaccine at 12 to 15 months . A new vaccine against Haemophilus influenzae type b has been licensed . Children aged 6 months and older with asthma, diabetes, or heart disease should receive influenza vaccine . Children aged 2 years and older with asplenia, immunosuppression, and nephrotic syndrome may be candidates for pneumococcal immunization.

Biologicals, 1994 Dec, 22(4), 397 - 402
Difficulties in establishing a serological correlate of protection after immunization with Haemophilus influenzae conjugate vaccines; Kayhty H; In several studies the protective concentration of anti-Haemophilus influenzae type b (Hib) capsular polysaccharide (PS) antibodies has been concluded to be around 0.04 to 0.20 microgram/ml . After the Finnish Hib polysaccharide vaccine trial it was estimated that 1 microgram/ml has to be achieved to predict long term protection after vaccination . These estimates of protective anti-Hib PS antibody concentrations were based on the assumption that protection from invasive Hib disease is mediated by antibodies and the role of cell-mediated immunity is negligible . This assumption was justified since the Hib PS is a T cell-independent antigen . The matter becomes quite different when the character of the PS vaccine is altered by conjugating it to a protein carrier, so that it acquires the ability to stimulate T cells, and the immunological memory plays a role in the protection . The immunized infants are thought to be able to respond with a rapid and high antibody response after exposure to the organism . After immunization with conjugate vaccines, protection can be seen at a lower serum antibody concentration than after polysaccharide vaccine . In addition, higher avidity of anti-Hib PS antibodies is associated with the response to conjugate than PS vaccine, and there are differences between the conjugates . This might have an influence on the functional activity of the antibodies . Hib conjugate vaccines are also able to reduce the carriage rate of Hib . This should be kept in mind when estimating what is needed from protective immune response after immunization with Hib conjugate vaccines.

Biologicals, 1994 Dec, 22(4), 339 - 45
Combination of DTP and Haemophilus influenzae type b conjugate vaccines can affect laboratory evaluation of potency and immunogenicity; Redhead K et al.; A commonly used Diphtheria-Tetanus-Pertussis (whole-cell) vaccine was combined with each of three different Haemophilus influenzae type b (Hib) capsular polysaccharide vaccines . Each Hib vaccine incorporated one of three different protein conjugates: tetanus toxoid, diphtheria CRM197 toxoid or group B Neisseria meningitidis outer membrane vesicles . The effects of these combinations on the subsequent laboratory control testing were examined . The addition of the Hib vaccines had no significant effect on the reactogenicity or the potency of the whole-cell pertussis component . The potency of, and antibody responses to, the diphtheria component were also unaffected in all three combinations . However, combination with the Hib vaccine comprising polysaccharide conjugated to tetanus toxoid had dramatic effects on tetanus potency and immunogenicity when assayed in mice . This combination resulted in a five-fold potentiation of the tetanus potency and a similarly large increase in the antibody responses to tetanus toxin and toxoid . The level of the antibody response to the Hib polysaccharide in this vaccine was also elevated, more than 20-fold, as a result of the combination . Such phenomena were not evident with combinations involving the other two Hib vaccines . These results have implications for the control testing of combined vaccines containing a whole-cell pertussis component and Hib polysaccharide-tetanus protein conjugate vaccine.

Br J Biomed Sci, 1994 Dec, 51(4), 307 - 11
Outer membrane protein profiling to distinguish between Haemophilus aegyptius and non-capsulate Haemophilus influenzae biotype III; Leaves NI et al.; Outer membrane protein profiling was used to assist in determining the identity of an isolate of Haemophilus spp . that was presumptively identified as non-capsulate Haemophilus influenzae biotype III . The possibility that this strain was in fact Haemophilus aegyptius was queried because of clinical information and the source of the isolate . Sodium dodecyl-sulphate polyacrylamide gel electrophoresis was used to establish the identity of the isolate as non-capsulate H . influenzae biotype III and no H . aegyptius . Generally, protein profiling compared very favourably with other standard tests for identifying H . aegyptius: the method was easily and rapidly performed and gave an unequivocal result.

J Antimicrob Chemother, 1994 Dec, 34(6), 1031 - 6
Serotypes and antimicrobial susceptibility of Haemophilus influenzae; Hussey G et al.; During a one year prospective study of Haemophilus influenzae infections in patients treated in hospitals in the metropolitan area of Cape Town . H . influenzae type b accounted for 81.7% of 126 invasive isolates, whereas 86.1% of the 280 non-invasive isolates were non-typeable . Ampicillin resistance was detected among 10.8% of strains of which all but one produced beta-lactamase . All strains were susceptible to cefotaxime as were more than 95% to chloramphenicol, rifampicin, tetracycline but 20.4% were resistant to co-trimoxazole and 87.2% to erythromycin.

Aust J Public Health, 1994 Dec, 18(4), 394 - 400
An economic analysis of alternatives for childhood immunisation against Haemophilus influenzae type b disease; McIntyre P et al.; Cost-effectiveness and cost-utility analyses of immunisation strategies against invasive Haemophilus influenzae type b (Hib) disease in Australia were based on a hypothetical birth cohort of 250,000 non-Aboriginal Australian children . The model predicted that, without immunisation, 625 cases of invasive Hib disease would occur in under-five-year-olds, with direct costs of $10.2 million . Universal public sector vaccination beginning before six months of age (6MVAC) prevented 80 per cent of cases; vaccination at 12 months (12MVAC) 62 per cent and at 18 months (18MVAC) 46 per cent . At a vaccine cost of $15 per dose, 18MVAC gave the lowest cost per quality-adjusted life year (QALY) over a wide range of model assumptions, with 6MVAC the 'best' alternative . The best estimate ($ per QALY) for 6MVAC was $6930 (three doses), for 12MVAC $9136 (two doses) and for 18MVAC $1231 (one dose) . The cost per QALY of single dose catch-up immunisation of older children was estimated at $8630 at two years, $27,000 at three years and $117,000 at four years if done at a scheduled visit; these values were increased if an additional medical visit was included . The threshold cost per vaccine dose at which an immunisation program became cost-saving was estimated for 6MVAC, 12MVAC and 18MVAC as $11, $10 and $14 . Even under a worst-case scenario, an immunisation program at 6, 12 or 18 months became cost-saving if indirect costs of death were included . Comparison with previous analyses revealed the importance of the incidence and age distribution of disability and assumptions about vaccine administration costs in determining model outcomes.

Mol Microbiol, 1994 Dec, 14(5), 843 - 50
Iron piracy: acquisition of transferrin-bound iron by bacterial pathogens; Cornelissen CN et al.; The mechanism of iron utilization from transferrin has been most extensively characterized in the pathogenic Neisseria species and Haemophilus species . Two transferrin-binding proteins, Tbp1 and Tbp2, have been identified in these pathogens and are thought to be components of the transferrin receptor . Tbp1 appears to be an integral, TonB-dependent outer membrane protein while Tbp2, a lipoprotein, may be peripherally associated with the outer membrane . The relative contribution of each of these proteins to transferrin binding and utilization is discussed and a model of iron uptake from transferrin is presented . Sequence comparisons of the genes encoding neisserial transferrin-binding proteins suggest that they are probably under positive selection for variation and may have resulted from inter-species genetic exchange.

Eur Respir J, 1994 Dec, 7(12), 2109 - 16
Effect of Haemophilus influenzae endotoxin on the synthesis of IL-6, IL-8, TNF-alpha and expression of ICAM-1 in cultured human bronchial epithelial cells; Khair OA et al.; Although studies of infective lung diseases have demonstrated that Haemophilus influenzae is a major pathogen, the mechanisms underlying pathogenesis by this organism are not clear . We have cultured human bronchial epithelial cells (HBEC) to confluency and have investigated the effect of H . influenzae endotoxin (HIE) on: 1) epithelial permeability, by movement of 14C-bovine serum albumin (14C-BSA) across HBEC and measurement of electrical resistance of HBEC; 2) release of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) into the supernatant, by enzyme-linked immunosorbent assay (ELISA); and 3) expression of intercellular adhesion molecule-1 (ICAM-1), by immunofluorescence staining . HIE did not significantly increase the movement of 14C-BSA across HBEC . In contrast, HIE progressively increased the electrical resistance of HBEC, such that this was significant after 24 h . Compared with untreated cells, 10-100 micrograms.ml-1 HIE-treated cells released significantly greater amounts of IL-6, IL-8 and TNF-alpha, after 24 h, which was blocked by 10(-5) M hydrocortisone . Similarly, incubation of HBEC with 10-100 micrograms.ml-1 HIE, significantly increased the total number of ICAM-1 positive cells, which were significantly decreased on incubation of the cells in the presence 10(-5) M hydrocortisone . Conditioned medium from HIE-exposed HBEC lead to significant increase in neutrophil chemotaxis and adhesion to endothelial cells in vitro . These results suggest that HIE may affect epithelial cell function and influence inflammation of the airway mucosa via induction of proinflammatory mediators.

J Biochem (Tokyo), 1994 Dec, 116(6), 1281 - 6
Two forms of restriction enzyme HindIII; Takasaki Y; Restriction endonuclease HindIII was purified from Haemophilus influenzae Rd . Two active fractions, P1 and P2, were obtained in phosphocellulose chromatography . HindIII could be purified completely from the first fraction, P1, by subsequent DEAE-cellulose chromatography . The second fraction, P2, showed HindIII activity higher than that of P1, though it was still contaminated with some minor proteins . The HindIII in P2 fraction showed differences in stability, binding to substrate DNA, electrophoretic mobility, etc., from the HindIII in P1 fraction . It is likely that there are two forms of HindIII in the bacterial cell . The endonuclease HindIII in P2 fraction was finally purified by DNA-cellulose chromatography, though considerable loss of enzymatic activity resulted . Upon infection of the cells with phage T4, the P2 fraction in phosphocellulose chromatography almost disappeared . The presence of two forms of HindIII may be related to bacterial defense against viral infection.

Diagn Microbiol Infect Dis, 1994 Dec, 20(4), 187 - 93
Development of a polymerase chain reaction assay to detect the presence of Streptococcus pneumoniae DNA; Friedland LR et al.; In this study, we have developed a chemically sensitive and specific polymerase chain reaction (PCR) assay to detect the presence of Streptococcus pneumoniae genomic DNA . The target DNA sequence was a 322-base pair segment of the S . pneumoniae DNA polymerase I gene (pol I) . PCR products of pure cultures of a set of pneumococcal serotypes commonly associated with human infection could be amplified in water and in blood cultures of clinical isolates containing S . pneumoniae . We were able to detect 2 fg of purified S . pneumoniae DNA . There were no false-positive reactions when the assay was performed on samples containing the following clinically encountered bacteria: Haemophilus influenzae type B, Neisseria meningitidis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas spp . nontypeable H . influenzae, Staphylococcus aureus, coagulase-negative staphylococci, and Streptococcus pyogenes . The addition of EDTA and citrate-anticoagulated whole blood to the PCR reaction mixture inhibited the PCR assay, whereas the addition of lithium heparin, sodium heparin, and sodium polyanetholesulfonate-anticoagulated whole blood to PCR reaction mixture did not interfere with the ability to detect the presence of S . pneumoniae DNA.

J Vet Med Sci, 1994 Dec, 56(6), 1191 - 3
Measurement of antibody titer to fowl pox virus by enzyme-linked immunosorbent assay; Iritani Y et al.; The usefulness of the measurement of antibody titer to fowl pox virus (FPV) by enzyme-linked immunosorbent assay (ELISA) was evaluated in SPF chickens with or without inoculation with FPV . The optimum concentration of purified antigen was 10 micrograms/ml of protein . The absorbance at 492 nm was less than 0.10 in the chickens negative to FPV from 1 to 63 days old . By contrast, a higher titer was detected in SPF chickens with various FPVs inoculated into the wing web than in non-inoculated chickens . Moreover, there was no cross response to chicken sera immunized with Haemophilus paragallinarum, Marek's disease virus, Newcastle disease virus or infectious bronchitis virus . The titers increased after vaccination were not increased after subsequent challenge with virulent FPV . These findings suggested the usefulness of the measurement of the antibody response to FPV vaccine by ELISA.

Eur J Epidemiol, 1994 Dec, 10(6), 699 - 702
Antibiotic susceptibility of 206 Haemophilus influenzae isolates collected from children in central Italy; Zanchi A et al.; Susceptibility of 206 H . influenzae isolates was evaluated by disk diffusion method for 11 antimicrobial agents . No isolates were found to be resistant to third-generation cephalosporins, amoxicillin+clavulanic acid, gentamicin and ciprofloxacin . Four untypable isolates (1.9%) were beta-lactamase producing ampicillin-resistant; one of these was also resistant to chloramphenicol . The rate of resistance against rifampin was 0.5 percent.

Southeast Asian J Trop Med Public Health, 1994 Dec, 25(4), 684 - 7
Etiology of acute lower respiratory infection in Filipino children under five years; Capeding MR et al.; This study conducted at the Research Institute for Tropical Medicine from April 1990 to December 1992, identified the etiology of acute lower respiratory tract infection (ALRI) in 119 (36.9%) of 317 hospitalized children < 5 years of age . A higher proportion of respiratory viruses (27.2%) than bacterial agents (10.7%) were identified . Viral agents (adenovirus, RSV, parainfluenza 3, influenza A and influenza B) and bacterial agents (mainly Haemophilus influenzae and Streptococcus pneumoniae) are the pathogenic agents involved in ALRI among Filipino children less than 5 years old.

Southeast Asian J Trop Med Public Health, 1994 Dec, 25(4), 672 - 7
Systemic Haemophilus influenzae disease in Thai children; Likitnukul S; Fifty patients with systemic Haemophilus influenzae disease were indentified by hospital chart review between 1980-1992 . The age distribution varied from 8 days to 14 years; the mean age of the patients was 12.7 months . The peak incidence was between 4 and 6 months of age . There were 27 male patients and 23 female patients for a male:female ratio of 1.17:1 . The relative frequencies of 79 clinical entities encountered in 50 patients are as follows: meningitis 55.7%, bacteremia 13.9%, pneumonia 25.3%, cellulitis 2.5% arthritis 1.3%, septic shock 1.3% . There were 23 patients (46%) who had more than one disease entity . Most of the patients were anemic (Hb < 10 gm%) when hospitalization . Sixty-four percent of the patients had early complications . The mortality rate was 8% . Although serotyping was not done from the isolates, at least 33 cerebrospinal fluid samples were positive for H . influenzae type b capsular antigen by counterimmunoelectrophoresis . The percentage of susceptible H . influenzae to penicillin, ampicillin, chloramphenicol, co-trimoxazole were 57.1%, 76.4%, 87.5% and 54.2%, respectively . There was no strain resistant to third generation cephalosporin . Our data indicate that H . influenzae is a serious and life threatening infection . Early diagnosis and proper treatment will reduce the morbidity and mortality rates . For prevention of infection, an appropriate strategy for vaccination is required.

Mol Microbiol, 1994 Dec, 14(5), 1077 - 92
The dipeptide permease of Escherichia coli closely resembles other bacterial transport systems and shows growth-phase-dependent expression; Abouhamad WN et al.; The dipeptide permease (Dpp) of Escherichia coli transports peptides consisting of two or three L-amino acids . The periplasmic dipeptide-binding protein (DBP), encoded by the dppA gene, also serves as a chemoreceptor . We sequenced the dpp locus, which comprises an operon of five genes, dppABCDE . Its organization is the same as the oligopeptide permease (opp) operon of Salmonella typhimurium and the spo0K operon of Bacillus subtilis . The dpp genes are also closely related to the hbpA gene, which encodes a haem-binding lipoprotein, and four other genes in an unlinked operon of unknown function in Haemophilus influenzae . Each Dpp protein has an Opp, Spo0K and H . influenzae homologue . Transcription of the dpp operon initiates 165 bases upstream of the predicted dppA start codon . The start site for transcription is preceded by potential -35 and -10 regions of a sigma 70 promoter . During exponential growth in Luria-Bertani (LB) broth, the level of dpp mRNA increases in two steps, one between A590 0.2 and 0.4 and one between A590 0.7 and 1.0 . The 310 nucleotides between dppA and dppB include a RIP (repetitive IHF-binding palindromic) element, whose deletion from a multi-copy plasmid causes fivefold and 10-fold reductions in the levels of upstream and downstream dpp mRNA, respectively.

Eur J Clin Microbiol Infect Dis, 1994 Dec, 13(12), 1038 - 45
Development of a ribotyping scheme for Haemophilus influenzae type b; Leaves NI et al.; Ribotyping and outer-membrane protein subtyping were used to characterise 283 consecutive isolates of Haemophilus influenzae type b . These isolates were obtained primarily from patients with invasive disease in the UK and were received by the Public Health Laboratory Service Haemophilus Reference Laboratory prior to the implementation of Haemophilus influenzae serotype b vaccine in the UK . A subtyping scheme using the ribotyping method is suggested . Twenty-two ribotypes are described, 14 of which were found amongst the 283 clinical isolates characterised in this study . In contrast, only four outer-membrane protein subtypes were found amongst the 283 isolates . The ribotyping profiles were further used to estimate the relatedness of isolates . The resulting dendrogram suggested a population genetic structure different from that previously described for Haemophilus influenzae type b using multi-locus enzyme electrophoresis . This study shows the value of ribotyping as a subtyping method for epidemiological studies of Haemophilus influenzae type b . However, the further use of ribotyping for population genetic structure analysis of Haemophilus influenzae type b may be misleading and therefore inappropriate.

Fortschr Med, 1994 Nov 30, 112(33), 485 - 8
{Respiratory tract infections: how frequent is antibiotic resistance? In vitro activity of older and recent antibiotics against the significant pathogens}; Ruckdeschel G; Presumably influenced by the new cost-saving health care regulations, more of the long-established antibiotics are now being prescribed . This fact prompted the present study on the current resistance profiles of such antibiotics used to treat major pathogens responsible for airway infections . A total of 202 strains of Streptococcus pneumoniae, Streptococcus pyogenes, Moraxella catarrhalis and Haemophilus influenzae were investigated . Sensitivity was determined using the agar dilution test for doxycycline, erythromycin, penicillin G, amoxicillin-clavulanic acid and cefpodoxime . In the case of such older antibiotics as doxycycline, erythromycin and amoxicillin, certain shortcomings in their efficacy against these common pathogens were found, while the bacteria were all sensitive to a combination of amoxicillin and clavulanic acid and to the oral cephalosporin, cefodoxime . In order to avoid the risk of ineffectivity in the treatment of infection of the airways, it is recommended that in Germany a new oral cephalosporin or a combination of an aminopenicillin and a beta-lactamase inhibitor be used.

Arch Intern Med, 1994 Nov 28, 154(22), 2589 - 96
Microbiology of community-acquired bacterial pneumonia in persons with and at risk for human immunodeficiency virus type 1 infection . Implications for rational empiric antibiotic therapy; Burack JH et al.; BACKGROUND: Bacterial pneumonia is a very common cause of morbidity and mortality among persons with human immunodeficiency virus; however, the microbiologic characteristics (including antibiotic resistance) of bacterial pathogens causing community-acquired pneumonia in this population have not been well characterized or correlated with potentially predictive clinical presentation characteristics . METHODS: We conducted a retrospective cohort study of all adults known to have or to be at high risk for human immunodeficiency virus infection and hospitalized at San Francisco (Calif) General Hospital from May 1990 through April 1991, with a hospital discharge diagnosis of community-acquired bacterial pneumonia and for whom a medical records review confirmed that this diagnosis met a uniform case definition . RESULTS: Two hundred sixteen eligible patients had one or more hospital admissions meeting the case definition . One or more etiologic pathogens were definitively identified in 75% of cases, with Streptococcus pneumoniae, Haemophilus species, Staphylococcus aureus, and gram-negative bacilli most frequently identified . In patients who had a bacteriologic diagnosis made, 18.6%, 6.8%, and 4.3% had pneumonia caused by pathogens resistant to ampicillin sodium, cefuroxime sodium, or trimethoprim-sulfamethoxazole, respectively . One hundred percent of pathogens isolated were susceptible to ceftazidime . Anemia and use of antibacterial medication at the time of hospital admission were the only independent predictors of ampicillin and cefuroxime resistance . CONCLUSION: Nearly one fifth of human immunodeficiency virus-associated community-acquired bacterial pneumonias requiring hospitalization were caused by ampicillin-resistant pathogens, and presenting clinical characteristics did not consistently define a subset of patients at lower risk for resistance . In the absence of a diagnostic sputum Gram's stain and pending definitive microbiologic diagnosis, initial empiric therapy should be with a second- or third-generation cephalosporin or possibly trimethoprim-sulfamethoxazole.

BMJ, 1994 Nov 26, 309(6966), 1412 - 4
Prospective study of bacterial meningitis in North East Thames region, 1991-3, during introduction of Haemophilus influenzae vaccine; Urwin G et al.; OBJECTIVE--To describe the epidemiology of primary bacterial meningitis in the North East Thames region over a three year period before and during the introduction of the vaccine for Haemophilus influenzae type b . DESIGN--Analysis of information on cases of primary bacterial meningitis identified by microbiology laboratories in the region, with collection of case data by questionnaire . MAIN OUTCOME MEASURES--Annual incidence rates for types of meningitis according to age and ethnic group . RESULTS--The annual incidence rates for the three major causes of bacterial meningitis in the general population were 1.9/100,000 for Neisseria meningitidis, 1.6/100,000 for Haemophilus influenzae before vaccination, and 1.0/100,000 for Streptococcus pneumoniae . Higher rates of H influenzae meningitis were found in Asians compared with white people (3.6/100,000 v 1.5/100,000, P = 0.01) . As a result of the vaccine programme introduced in October 1992 the number of cases of H influenzae meningitis in children under 5 years has fallen by 87% . CONCLUSIONS--Bacterial meningitis is a serious problem especially in preschool children . There are differences in the incidence of some causes of bacterial meningitis in different ethnic groups; with H influenzae type b being significantly more common among black and Asian people than among white people . The immunisation programme for H influenzae type b in the North East Thames region has been successful in reducing the incidence of this type of meningitis in Asian and white populations . The numbers were too small to evaluate in the black population.

Med Clin (Barc), 1994 Nov 12, 103(16), 611 - 4
{Clinico-epidemiologic study of bacterial meningitis in Aragon}; Ara JR et al.; BACKGROUND: The aim of the present study was to know the incidence, etiology, prognostic factors and rate of mortality of bacterial meningitis in Aragon (Spain) . METHODS: The clinical records of all the patients with bacterial meningitis seen in the hospitals in Aragon (Spain), from 1985 to 1988 inclusive were reviewed . RESULTS: The mean of the annual rates of incidence for Aragon (Spain) was 7.52/100,000 inhabitants . In patients under the age of 15 years the most frequent etiologies were Neisseria meningitidis (59.0%), Haemophilus influenzae (13.7%) and Streptococcus pneumoniae (9.4%); the global rate of mortality was 3.5% similar to that of sequelae . In those over the age of 14 years, the most frequent etiologies were N . meningitidis (33%), S . pneumoniae (18.4%) and Staphylococcus spp . (13.6%); the rate of global mortality was 19.5% and that of sequelae 10.8% with resistance of S . pneumoniae to penicillin and/or ampicillin in 45.5% of the cases in children and in 26.3% in adults . No significant evolutive differences related with the existence of resistances or the administration of antibiotics prior to lumbar punction were observed in any of the age groups . CONCLUSIONS: N . meningitidis is the main etiologic agent in Aragon in both children and adults . The greatest rates of mortality and sequelae were observed in the youngest and oldest age groups with a similar relation being seen in infection by gramnegative bacilli and S . pneumoniae, thus making these patients to be considered as being at high risk.

Biochemistry, 1994 Nov 8, 33(44), 13070 - 8
Structure of the major oligosaccharide from the lipooligosaccharide of Haemophilus ducreyi strain 35000 and evidence for additional glycoforms; Melaugh W et al.; Haemophilus ducreyi is a sexually transmitted pathogen that colonizes the genital epithelium in humans, causing genital ulcers or chancroid . Its surface lipooligosaccharides (LOSs) have been shown to play a role in ulcer formation and may also be important in cell adhesion and invasion of host tissue . Earlier we presented a preliminary structure of the major LOS from strain 35000 that suggested the presence of terminal lactosamine {Melaugh, W., Phillips, N.J., Campagnari, A.A., Karalus, R., & Gibson, B . W . (1992) J . Biol . Chem . 267, 13434-13439} . We have now confirmed this structure and assigned the anomeric linkages by 2D NMR studies . In addition to this major structure, analysis by electrospray ionization mass spectrometry of both O-deacylated LOSs and the oligosaccharides released after treatment with mild acid indicates the presence of several other LOS glycoforms . These glycoforms constitute a series of both truncated and elongated analogs of the major oligosaccharide determined by NMR . One of these glycoforms exists as a smaller oligosaccharide corresponding to the major structure minus terminal galactose . Three other glycoforms appear as larger molecular weight species formed by the addition of phosphoethanolamine, N-acetylhexosamine, and N-acetylhexosamine plus hexose . Two sialylated glycoforms were also identified and subsequently confirmed by treatment with neuraminidase, but these glycoforms were not found in the released oligosaccharide pool due to the acid lability of of sialic acid . This study clearly indicates that the LOSs from H . ducreyi strain 35000 exist as a heterogeneous population whose structures differ primarily in their phosphorylation states and terminal sugars and whose terminal glycan structures can resemble those of human antigens.

JAMA, 1994 Nov 2, 272(17), 1358 - 60
Acute epiglottitis in adults . Analysis of 129 cases; Frantz TD et al.; OBJECTIVE--To characterize the clinical features of acute epiglottitis in adults and to identify factors associated with airway intervention . DESIGN--Case series . SETTING--Northern California health maintenance organization . PARTICIPANTS--A total of 129 patients aged 18 years or older with laryngoscopically confirmed acute epiglottitis admitted from November 1986 through October 1991 . RESULTS--The mean patient age was 47 years (range, 18 to 85 years) and the male-to-female ratio was 1.8 to 1.0 (P < .001) . The most common symptoms were sore throat (95%) and odynophagia (94%); the most common signs were muffled voice and evidence of pharyngitis . Nineteen patients (15%) received airway intervention, including seven with tracheotomy and 12 with endotracheal intubation . The remaining 110 patients recovered fully without airway intervention . In multivariate analysis, factors associated with airway intervention were stridor (relative risk {RR}, 6.2; 95% confidence interval {CI}, 1.7 to 22.9) and sitting erect (RR, 4.8; 95% CI, 1.3 to 16.1) . Six (12%) of 52 blood cultures yielded Haemophilus influenzae type b . Major complications occurred in six patients (5%), but no deaths occurred . CONCLUSION--Most adults who have acute epiglottitis can be managed conservatively and have low morbidity and mortality.

South Med J, 1994 Nov, 87(11), 1083 - 7
Haemophilus influenzae type B invasive disease in urban and rural children: immunization patterns and prevalence of disease; Rathore MH et al.; To examine the impact of the introduction of Haemophilus influenzae type b (Hib) conjugate vaccine, we reviewed the incidence of Hib invasive disease in the state of Florida from 1984 to 1992 . We analyzed the incidence of disease in two populations of children, one residing in an urban area and the other in a rural area . This study was designed to compare incidence rates prior to and following the introduction of Hib vaccine for children . Our data show a > 80% decrease in the incidence of Hib invasive disease in the state of Florida and a similar decrease in both the urban and rural populations examined . Analysis of the data revealed that the majority of children contracting Haemophilus influenzae type b invasive disease in both populations were either not immunized or were only partially immunized.

Laryngoscope, 1994 Nov, 104(11 Pt 1), 1314 - 22
Changing patterns in pediatric supraglottitis: a multi-institutional review, 1980 to 1992; Senior BA et al.; Supraglottitis is a rapidly progressive, life-threatening airway emergency in pediatric patients typically caused by Haemophilus influenzae type B (HIB) . With distribution of the first efficacious vaccine for HIB in April 1985, changing disease patterns have begun to emerge; however, certain characteristics have remarkably persisted . The authors reviewed 252 pediatric patients with acute supraglottitis spanning the prevaccination and postvaccination years 1980 to 1992 at three major regional pediatric hospitals in Massachusetts, Ohio, and California, as well as at two community hospitals in Massachusetts . Findings include a decline in disease prevalence in all geographic areas with demographic, etiologic, and management evolution all seen . Children who had been immunized yet developed supraglottitis have been examined as predictive of future trends.

J Bacteriol, 1994 Nov, 176(22), 6789 - 94
The Haemophilus influenzae sxy-1 mutation is in a newly identified gene essential for competence; Williams PM et al.; The sxy-1 mutation of Haemophilus influenzae causes a 100- to 1,000-fold increase in spontaneous natural competence . We have used mapping and sequencing to identify this mutation as a G-to-A transition in an open reading frame adjacent to the rec-1 locus . This mutation substitutes valine for isoleucine at amino acid 19 of the protein specified by this gene (now named sxy) . A multicopy plasmid containing the wild-type sxy gene confers constitutive competence on wild-type cells . Cells carrying this plasmid exhibit, in all stages of growth, DNA uptake levels and transformation frequencies as high those normally seen only after full induction of competence by starvation; deletion of part of the sxy gene from the plasmid abolishes this effect . In contrast, a transposon insertion in sxy entirely prevents both DNA uptake and transformation, indicating that sxy encodes a function essential for competence . These findings suggest that sxy may act as a positive regulator of competence . However, because cells carrying the transposon-inactivated sxy::Tn allele grow slowly under conditions that do not induce competence, sxy may also have a role in noncompetent cells.

Infect Immun, 1994 Nov, 62(11), 4922 - 8
Identification of hifD and hifE in the pilus gene cluster of Haemophilus influenzae type b strain Eagan; McCrea KW et al.; Haemophilus influenzae produces surface structures called pili that promote adherence to human cells . Three genes encoding the major pilus structural component (pilin), chaperone, and usher proteins (designated hifA, -B, and -C, respectively) have been identified previously . In this study, transposon mutagenesis and DNA sequence analysis identified two open reading frames (ORFs) downstream of, and in the same orientation as, hifC . These genes have been designated hifD and hifE . Both genes have predicted C-terminal amino acid homology to HifA, and mutations in either gene resulted in the loss of morphologic and functional pili, indicating that hifD and hifE encode pilus structural components and are required for pilus expression . Another ORF, identified immediately downstream of hifE, has a predicted amino acid sequence that is 70% identical to an aminopeptidase of Escherichia coli called PepN, and a mutation within this ORF did not alter pilus expression . These data indicate that the pepN homolog is not required for pilus biogenesis and that one end of the pilus gene cluster has been defined.

Infect Immun, 1994 Nov, 62(11), 4855 - 60
Characterization and virulence analysis of catalase mutants of Haemophilus influenzae; Bishai WR et al.; In addition to detoxifying peroxides generated by aerobic metabolism, the catalases of pathogenic bacteria have also been hypothesized to serve as virulence factors by enabling microorganisms to resist the oxidative bursts of host inflammatory cells . Using transposon mutagenesis of the hktE gene, encoding the Haemophilus influenzae structural gene for catalase, we constructed defined catalase mutants of H . influenzae strains Rd- and Eagan b+ . These mutants show no detectable catalase production during exponential or stationary phases or following induction with hydrogen peroxide or ascorbic acid, indicating that hktE is the only functional hydroperoxidase gene present in these two strains of H . influenzae . Exponential-phase cultures of hktE mutants are 8- to 25-fold more sensitive to hydrogen peroxide than the wild type . Using the infant rat model, hktE mutants of strain Eagan b+ were 2.3-fold less virulent than the wild type following intraperitoneal inoculation (P = 0.07) . When administered intranasally, the Eagan b+ hktE mutant produced wild-type levels of bacteremia and nasal colonization . The results of this study show that while the H . influenzae hktE gene is important for survival in the presence of peroxides, deletion of the gene produces only a modest reduction in ability to cause lethal sepsis following parenteral challenge and no change in ability to colonize following intranasal inoculation in the infant rat model of infection.

Infect Immun, 1994 Nov, 62(11), 4848 - 54
Protein D, the glycerophosphodiester phosphodiesterase from Haemophilus influenzae with affinity for human immunoglobulin D, influences virulence in a rat otitis model; Janson H et al.; A mutant lacking the ability to express the surface-exposed lipoprotein protein D was constructed by linker insertion and deletion mutagenesis of a cloned DNA insert containing the protein D structural gene from a nontypeable Haemophilus influenzae strain (NTHi) . An isogenic NTHi mutant was isolated after transformation of genetically competent bacteria . The transformant was unreactive to a protein D-specific monoclonal antibody in a colony immunoassay . In addition, the mutant lacked the ability to synthesize detectable levels of protein D by protein staining, immunoblot methods, glycerophosphodiester phosphodiesterase activity, and binding studies of radiolabelled immunoglobulin D . The isogenic protein D-deficient mutant was compared with its parental strain for its ability to induce experimental otitis media in rats challenged with bacteria . An approximately 100-times-higher concentration of the mutant compared with that of the wild-type strain was required in order to cause otitis among all rats challenged with that given dose . The protein D mutant exhibited a generation time that was equal to that of the wild-type strain in complex broth medium . No difference in lipopolysaccharide expression was found between the mutant and the parental strain . These results suggest that protein D may influence the pathogenesis of NTHi in the upper respiratory tract.

Vaccine, 1994 Nov, 12(15), 1460 - 6
Interaction of Haemophilus influenzae type b conjugate vaccines with diphtheria-tetanus-pertussis vaccine in control tests; Redhead K et al.; The effects of combining three Haemophilus influenzae type b (Hib) capsular polysaccharide vaccines, conjugated to different proteins, with DTP vaccine on the subsequent control testing were examined . The addition of the Hib vaccines had little effect on the reactogenicity or the potency of the whole-cell pertussis component . The potency of, and antibody responses to, the diphtheria component were also unaffected in all three combinations . However, combination with the Hib vaccine comprising polysaccharide conjugated to tetanus toxoid resulted in a fivefold potentiation of the tetanus potency and large increases in the antibody responses to tetanus toxin and toxoid and Hib polysaccharide . These results have implications for the control testing of combined vaccines containing a whole-cell pertussis component and Hib polysaccharide-tetanus protein conjugate vaccine.

J Infect, 1994 Nov, 29(3), 283 - 7
Neonatal Haemophilus influenzae infections; al-Mofada SM; Thirteen cases of neonatal Haemophilus influenzae (HI) infections were identified in Al-Baha Region, Saudi Arabia during 1 year: seven male, six female . The mean weight and age were 36.0 weeks (28-44) and 2.5 kg (1.1-4.5) respectively . All babies were delivered outside the hospital, five at home and eight at primary care centres . HI was isolated from the lungs in 12 (92%), eyes in seven (54%), and from the blood in four (31%) . None of the neonates had meningitis . HI resistant to ampicillin and cefuroxime were identified in one case (7.7%) each . All survived and were discharged home in good condition . Our findings suggest that HI is becoming more recognised as a cause of neonatal infections especially in premature babies . The current starting regimen of antibiotics for suspected sepsis in neonates (ampicillin and gentamicin) adequately cover for HI sepsis and need not be changed unless lack of response to treatment is documented.

FEMS Immunol Med Microbiol, 1994 Nov, 10(1), 11 - 8
Bacterial crude extracts or ribosomes are recognized similarly by peripheral and mucosal B cells; Zanin C et al.; Bacterial ribosomes have been shown to induce effective humoral and cellular immunological responses to whole microorganisms . In this study, the numbers of specific antibody producing cells directed towards Klebsiella pneumoniae, Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae ribosomes or whole bacteria sonicates were compared in the peripheral blood and tonsils of 7 children, and in the tonsils, mesenteric and cervical lymph nodes of 10 sheep . No significant difference was noted between the two types of antigens, confirming that ribosomal preparations are able to mimic the immunogenicity of whole bacteria in the mucosae-associated lymphoid tissue.

Am J Otolaryngol, 1994 Nov-Dec, 15(6), 436 - 43
Haemophilus influenzae type B epiglottitis after immunization with HbOC conjugate vaccine; Keyser JS et al.; INTRODUCTION: US Food and Drug Administration (USFDA) has licensed four Haemophilus influenzae type B (Hib) vaccines for use in children . Haemophilus influenzae type B is by far the most common pathogen in childhood epiglottitis and it is hoped that with the introduction of the Hib vaccine that a corresponding decrease in epiglottitis cases will be appreciated . MATERIALS AND METHODS: A retrospective study of all children admitted with the diagnosis of epiglottitis for the 11-year period of 1982 to 1992 was conducted in order to determine the incidence of epiglottitis and Hib vaccine failure . Fifty-nine cases were included in the study by documentation of an inflamed epiglottis . The case of Hib epiglottitis in a 4-year-old child immunized with HbOC conjugate vaccine at 18 months of age is detailed . RESULTS: A statistically significant decrease was found in the incidence of epiglottitis since introduction of the vaccines; however, the overall trend in decrease for the 11-year period was not statistically significant . Vaccination status was difficult to accurately document with only two cases of vaccine failure identified . CONCLUSION: The incidence of Haemophilus influenzae type B epiglottitis at our regional Children's hospital has decreased since the introduction of the Hib vaccine . Reasons for vaccine failure are postulated.

J Rheumatol, 1994 Nov, 21(11), 2005 - 10
Analysis of the genes encoding the variable regions of human IgG rheumatoid factor; Ezaki I et al.; OBJECTIVE . To better understand the immunoglobulin variable (V) region repertoire of rheumatoid factors (RF) . METHODS . We characterized the heavy (H) and light (L) chain gene segments utilized in a monospecific IgG RF secreting hybridoma (AEE111F) which were derived from a patient with rheumatoid arthritis (RA) . The hybridoma was established by fusion of a mouse myeloma cell line with bone marrow derived mononuclear cells from a patient with RA . First strand complementary DNA (cDNA) was generated and used for a polymerase chain reaction amplification of the H and L chain V domains . The amplified V domains were sequenced and compared with an extensive database of germline and cDNA V gene segments . RESULTS . The VH sequence was found to be 96% homologous to a previously described fetal VH3 cDNA (60P2) . The VL sequence was also highly homologous to the previously described V lambda II gene (96%) derived from a patient with systemic lupus erythematosus which correlated with an 8.12 idiotype (Id), and to an antibacterial antibody against the Haemophilus influenzae type b capsular polysaccharide (94.7%) . CONCLUSION . The overlap among this RF VL gene and the 2 reported V lambda sequences of antibodies that expressed anti-DNA related Id and an environmental pathogen specificity suggests that a part of the IgG RF isolated from patients with RA may thus be derived from the physiological natural antibody repertoire during an abnormal immune response and then develop high affinity, monospecific RF by the selection of an antigen driven mechanism.

Eur J Obstet Gynecol Reprod Biol, 1994 Nov, 57(2), 85 - 9
Laparoscopic study on the microbiology and severity of acute pelvic inflammatory disease; Heinonen PK et al.; OBJECTIVE: To study the microbiologic findings in relation to the severity of acute pelvic inflammatory disease (PID) . STUDY DESIGN: Of 72 women with acute PID verified and graded by laparoscopy and endometrial histopathology, 37 had mild PID and 35 had severe PID . Cervical, endometrial and tubal cultures were obtained for Chlamydia trachomatis, Neisseria gonorrhoeae, genital mycoplasmas, facultative and anaerobic bacteria and herpes simplex virus . RESULTS: C . trachomatis was the primary pathogenic agent in 44% of patients with acute PID . C . trachomatis and N . gonorrhoea were as common in both severity groups, although C . trachomatis was isolated significantly more frequently from the fallopian tubes among cases with severe PID . Where aerobic or facultative bacteria other than C . trachomatis or N . gonorrhoeae were concerned, Escherichia coli and Haemophilus influenzae were the most important aerobic bacteria isolated from the fallopian tubes . Anaerobic bacteria were recovered from the fallopian tubes significantly more frequently in cases with severe PID than in those with mild PID, whereas their presence in the endometrium was not related to the severity of PID . CONCLUSIONS: The role of C . trachomatis as the leading cause of PID was confirmed in both laparoscopically mild and severe PID . Severe PID with abscess is invariably a polymicrobial infection with anaerobic bacteria involved, whereas their role in affecting the outcome of mild PID as well as the need of antianaerobic antimicrobial therapy in mild PID remains questionable.

Jpn J Antibiot, 1994 Nov, 47(11), 1559 - 64
{Clinical studies on cefozopran in pediatrics}; Haruta T et al.; Cefozopran (CZOP) was administered via intravenous injection to 9 patients (ages ranging from 1 month to 13 years) with pediatric bacterial infections, at daily dose levels between 56.7 and 200 mg/kg, divided into 3 or 4 doses . The following results were obtained . 1 . Eight patients, including 1 with purulent meningitis, 1 with sepsis, 3 with acute pneumonia and 3 with lymphadenitis, were treated and subjected to clinical evaluation . Clinical effects were excellent in 6 cases and good in 2, with an overall efficacy rate of 100% . One case with pyoderma was not evaluated because of a combined use of an external antibiotic . 2 . Organisms suspected as pathogens included 5 strains: 3 strains of Haemophilus influenzae, 1 strain of Staphylococcus aureus and 1 of Escherichia coli . Bacteriologically, all the strains were eradicated . 3 . Side effects or abnormal laboratory test results were observed in 4 cases; wheal in 1 case, elevated GOT and GPT in 2 cases and eosinophilia in 1 case . 4 . From the results described above, we considered that CZOP would be an effective drug for use in pediatric bacterial infections.

Jpn J Antibiot, 1994 Nov, 47(11), 1536 - 43
{Pharmacokinetic and clinical studies of cefozopran in the field of pediatrics}; Kitamura K et al.; Cefozopran (CZOP) was administered intravenously to 22 infants (aged 3 months to 15 years) with infections excluding suppurative meningitis in doses of 10 to 40 mg/kg 3 to 4 times daily for periods of 3 to 16 days and its efficacy and safety in infantile infections as well as pharmacokinetic parameters were determined . The half-lives of CZOP after intravenous administration at doses of 10, 20 and 40 mg/kg were 2.84, 2.36 +/- 0.67, and 2.48 hours, respectively . The rates of recovery in the urine within 6 hours of administration were 83.6%, 62.9 +/- 23.1%, and 77.3%, respectively . The subjects for whom drug responses were evaluable consisted of 1 case of suppurative meningitis, 8 cases of respiratory tract infection, 2 cases of urinary tract infection, 2 cases of oral infection, 2 cases of pharyngotonsillitis, 1 case of skin soft tissue infection, and 1 case of external otitis, totaling 17 cases . The efficacy rate was 88.2% . The drug proved so effective on suppurative meningitis in particular that the patient was healed without leaving any sequela behind . Seven strains were identified as causative pathogens (5 strains of Haemophilus influenzae, 1 strain of Staphylococcus aureus, 1 strain of group B Streptococcus) isolated from 6 patients . All but 1 strain were eradicated (the rate of eradication 83.3%) . In the patients with suppurative meningitis the bacterial count of spinal fluid was markedly decreased 6 hours after drug administration and the organism was eradicated in 45 hours . Eruption was noted in 1 patient as a side effect of CZOP, but disappeared soon after discontinuation.(ABSTRACT TRUNCATED AT 250 WORDS)

Jpn J Antibiot, 1994 Nov, 47(11), 1457 - 63
{Pharmacokinetic, bacteriological and clinical studies on cefozopran in children}; Tajima T et al.; Pharmacokinetic, bacteriological and clinical studies on cefozopran (CZOP) were performed in children . The results were as followed: 1 . A total of 13 patients were treated with CZOP . The tested dose was 20 mg/kg (50 mg/kg in maxillary sinusitis), and the drug administered via intravenous bolus injection or 30-minute intravenous drip infusion 3 times daily, for 3-11 days . Clinical efficacies of CZOP in 13 patients with bacterial infections (11 with pneumonia, 1 with otitis media and 1 with maxillary sinusitis) were evaluated as excellent in 13 with an efficacy rate of 100% . Any adverse reactions or abnormal laboratory test results were not observed in any patients . Fourteen causative strains were found in 10 patients . Streptococcus pneumoniae in 4 cases out of 4, Streptococcus pyogenes in 1/1, Moraxella (Branhamella) catarrhalis in 3/3, Haemophilus influenzae in 4/6 were eradicated . 2 . Pharmacokinetic studies . The mean serum concentration immediately after intravenous drip infusion over 30-minute of 20 mg/kg was 39.1 micrograms/ml (range: 25.6-52.5 micrograms/ml) . The mean urinary recovery rate over 8 hours after administration was 49.0% (range: 45.2-51.8%) . Based on the above results and the broad spectrum and great antibacterial activity of CZOP, it is considered that CZOP is a promising antibiotic usable as a single agent for the primary therapy of acute bacterial infections ranging from mild to severe in children.

J Clin Microbiol, 1994 Nov, 32(11), 2871 - 2
Comparison of goat and horse blood as culture medium supplements for isolation and identification of Haemophilus influenzae and Streptococcus pneumoniae from upper respiratory tract secretions; Gratten M et al.; The results of this study show that goat blood as a culture medium supplement is as supportive as horse blood for the isolation and identification of Haemophilus influenzae and Streptococcus pneumoniae from clinical material . Care is required in the preparation of goat blood chocolate agar to ensure that a thermolabile growth inhibitor of NAD-dependent Haemophilus species is eliminated.

J Clin Microbiol, 1994 Nov, 32(11), 2846 - 50
Interpretive criteria for susceptibilities of Haemophilus influenzae to ampicillin, amoxicillin, and amoxicillin-clavulanic acid; Fuchs PC et al.; One hundred fifty isolates of Haemophilus influenzae (including 30 beta-lactamase-positive strains and 23 beta-lactamase-negative, ampicillin-resistant strains) were tested for susceptibilities to ampicillin, amoxicillin, and amoxicillin-clavulanic acid (A/C) by the broth microdilution method in Haemophilus test medium (HTM) and in Mueller-Hinton medium with lysed horse blood and by the disk diffusion method on HTM agar . Our results support the use of HTM for susceptibility testing of H . influenzae but raise a number of questions regarding the interpretive criteria currently in use, particularly with respect to the fourfold difference in MIC susceptibility breakpoints for ampicillin and A/C and a resulting high proportion of A/C-susceptible beta-lactamase-negative, ampicillin-resistant strains.

J Clin Microbiol, 1994 Nov, 32(11), 2786 - 90
Disk diffusion versus broth microdilution susceptibility testing of Haemophilus species and Moraxella catarrhalis using seven oral antimicrobial agents: application of updated susceptibility guidelines of the National Committee for Clinical Laboratory Standards; Kibsey PC et al.; Susceptibility testing of Haemophilus species and Moraxella catarrhalis is medium and inoculum dependent . Seven oral agents, ampicillin, amoxicillin-clavulanic acid, cefaclor, loracarbef, cefuroxime-axetil, cefixime, and erythromycin, were tested against 400 beta-lactamase-positive and -negative clinically significant respiratory strains of Haemophilus species and 100 strains of M . catarrhalis . Sources of the strains included teaching and regional hospitals and a private laboratory . All strains were tested by broth microdilution and disk diffusion in haemophilus test medium for Haemophilus species and Mueller-Hinton broth and agar for M . catarrhalis . Appropriate National Committee for Clinical Laboratory Standards (NCCLS) standards were followed . For Haemophilus species, by disk diffusion and broth microdilution, respectively, 27 and 27% of strains were resistant to ampicillin, 37 and 5% were resistant to erythromycin, 3 and 0.5% were resistant to cefaclor, 2 and 0.5% were resistant to loracarbef, and 0% were resistant to cefuroxime-axetil, cefixime, and amoxicillin-clavulanic acid . beta-Lactamase-negative ampicillin-resistant strains were not observed . Of M . catarrhalis strains, 56% were resistant to ampicillin by disk diffusion and 95% were resistant by broth microdilution . This species was susceptible to all other agents tested by either method . The disagreements between disk diffusion results and MICs for cefaclor, ampicillin, cefuroxime, and loracarbef that occurred with use of the 1990 NCCLS tables were resolved when the 1992 NCCLS tables were used.

J Clin Microbiol, 1994 Nov, 32(11), 2738 - 44
Detection of bacterial DNA in cerebrospinal fluid by an assay for simultaneous detection of Neisseria meningitidis, Haemophilus influenzae, and streptococci using a seminested PCR strategy; Radstrom P et al.; Primers specific to conserved and variable regions in the 16S rRNA sequence were selected from the partially sequenced 16S rRNA genes of Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae, S . agalactiae, and Staphylococcus epidermidis . The PCR assay was divided into two DNA amplifications . The first resulted in a general bacterial amplicon, and the second resulted in a species-specific amplicon . The high specificity of the PCR assay was documented after testing bacteria of 28 different species (133 strains) . A total of 304 clinical cerebrospinal fluid samples, including 125 samples from patients with bacterial meningitis, were assayed to investigate the diagnostic sensitivity and specificity for bacterial meningitis . The assay showed high sensitivity (0.94) and specificity (0.96) with the clinical samples, although some false results were obtained, the reasons for which are discussed . With agarose gel electrophoresis for detection of the PCR products, the detection limit for meningococci in cerebrospinal fluid was 3 x 10(2) CFU/ml.

J Clin Microbiol, 1994 Nov, 32(11), 2729 - 37
Development of PCR assays to detect ampicillin resistance genes in cerebrospinal fluid samples containing Haemophilus influenzae; Tenover FC et al.; We developed PCR primers specific for the blaTEM and blaROB ampicillin resistance genes . The specificity of the primers was confirmed by testing a series of Escherichia coli isolates containing a variety of ampicillin resistance genes and a series of ampicillin-resistant and ampicillin-susceptible Haemophilus influenzae isolates . There was a perfect correlation between ampicillin MICs, the presence of beta-lactamase (as determined by the nitrocefin test), and the results with the blaTEM and blaROB primers . Isolates of H . influenzae and Streptococcus pneumoniae obtained from 25 frozen cerebrospinal fluid (CSF) specimens were also tested . Four of 14 H . influenzae isolates were positive with the blaTEM primers; none were positive with the blaROB primers . Ampicillin MICs were determined for the H . influenzae isolates, and penicillin MICs were determined for the S . pneumoniae isolates . Only the four PCR-positive H . influenzae isolates had elevated MICs of ampicillin and were beta-lactamase positive . None of the H . influenzae isolates contained the blaROB gene, and none of the S . pneumoniae isolates produced positive reactions with either primer set . We then used universal primers directed to conserved regions of rRNA and a Haemophilus detection probe to identify which of the 25 frozen samples of CSF contained H . influenzae . Fourteen of the 25 CSF specimens were positive for H . influenzae, which correlated with the number of organisms obtained by culture of the CSF samples . Four of the CSF samples were positive with the blaTEM primer set, and these correlated with the four H . influenzae isolates that were positive when tested directly by PCR . The blaTEM assay required the use of native Taq polymerase because Amplitaq preparations were contaminated with vector DNA that contained the blaTEM-1 gene.

Pediatr Infect Dis J, 1994 Nov, 13(11), 983 - 9
Bacterial colonization of the nasopharynx predicts very early onset and persistence of otitis media in Australian aboriginal infants; Leach AJ et al.; Otitis media (OM) develops in the first months of life and persists throughout childhood in many rural Aboriginal children . We have followed Aboriginal and non-Aboriginal infants from birth to determine the relationship of the early onset of OM to nasopharyngeal colonization with respiratory pathogens . Aboriginal infants were colonized with multiple species of respiratory bacteria (Moraxella catarrhalis, Haemophilus influenzae, Streptococcus pneumoniae) at a rate of 5% per day and the timing of colonization predicted the onset of persistent OM in individual Aboriginal infants . Non-Aboriginal infants became colonized by M . catarrhalis alone at the slower rate of 1% per day and experienced transient episodes of OM in the absence of colonization . We attribute early bacterial colonization in most Aboriginal infants to high rates of cross-infection due to overcrowding, poor hygiene and high rates of bacterial carriage . Early age of infection and the multiplicity of bacterial types may contribute to prolonged carriage and to eustachian tube damage leading to persistent OM . Thus Aboriginal infants are "otitis-prone" and might qualify for prophylactic antibiotics.

Pediatr Infect Dis J, 1994 Nov, 13(11), 975 - 82
The etiology of pneumonia in malnourished and well-nourished Gambian children; Adegbola RA et al.; During a 2-year period 159 malnourished children ages 3 months to 5 years with radiologic evidence of pneumonia were investigated to determine the cause of their pneumonia . In addition 119 malnourished children without pneumonia, 119 well-nourished children with pneumonia and 52 well-nourished children without pneumonia were studied as controls . Percutaneous lung aspiration was performed on 35 malnourished and 59 well-nourished children with pneumonia . Bacteria were isolated from the blood, lung or pleural fluid of 28 (18%) malnourished children with pneumonia, 42 (35%) well-nourished children with pneumonia and from the blood of 5 (4%) malnourished children without pneumonia . Streptococcus pneumoniae and Haemophilus influenzae, which were the two organisms isolated most frequently in both groups of children with pneumonia, were found in 17 (11%) malnourished and 39 (33%) well-nourished children with pneumonia . Mycobacterium tuberculosis was detected in 5 malnourished children with pneumonia . A potentially pathogenic virus was identified in 35% of malnourished children with pneumonia and 40% of well-nourished children with pneumonia, and from 25% of children without pneumonia . The viruses identified most frequently were adenovirus and respiratory syncytial virus.(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: During November 1990-October 1992 in Banjul, Gambia, providers at a hospital enrolled 159 children with pneumonia and 119 children without pneumonia, 119 well-nourished children with pneumonia, and 52 well-nourished children without pneumonia into a study examining the bacteriologic and virologic etiology of pneumonia . Pneumonia was more common among children with marasmic kwashiorkor (12% of all malnourished children) than among other malnourished children (53% vs . 33%; p 0.05) . Most malnourished children (49%) were undernourished . 11% of all malnourished children had kwashiorkor . Laboratory personnel isolated bacteria from 28 (18%) malnourished children with pneumonia, 42 (35%) well-nourished children with pneumonia, and 5 (4%) malnourished children without pneumonia . Among all pneumonia cases, Streptococcus pneumoniae and Haemophilus influenzae were the most prevalent bacteria, especially among the well-nourished children (33% vs . 11%; p 0.001) . They were not present in malnourished children without pneumonia . Mycobacterium tuberculosis was isolated in 5 malnourished children with pneumonia . Pathogenic viruses were isolated more often from malnourished children with pneumonia and from well-nourished children with pneumonia than from children without pneumonia (35% and 40%, respectively, vs . 25%; p 0.01) . Most common pathogenic viruses were adenovirus and respiratory syncytial virus (RSV) . RSV was more common in well-nourished children with pneumonia than malnourished children with pneumonia (13% vs . 6%; p 0.05) . Herpes simplex virus was more common in malnourished children with pneumonia than well-nourished children (6% vs . 2%) . 25 children had both bacterial and viral pathogens . Only 4 children (all with pneumonia) had the measles virus . These findings suggest that S . pneumoniae and H . influenzae are probably the bacterial causes of pneumonia in both well-nourished and malnourished children in areas with rare cases of measles and kwashiorkor . In these areas, M . tuberculosis may be also a cause of pneumonia in malnourished children, especially if edema is present .

Infect Immun, 1994 Nov, 62(11), 4861 - 7
Identification of a new locus involved in expression of Haemophilus influenzae type b lipooligosaccharide; Jarosik GP et al.; Previous studies have shown that changes in the expression of the Haemophilus influenzae type b (Hib) lipooligosaccharide (LOS) epitope reactive with monoclonal antibody (MAb) 5G8 can be correlated with alterations in the virulence of some Hib strains . To identify the locus involved in expression of this particular LOS epitope, a genomic library was constructed in the plasmid shuttle vector pGJB103 from Hib strain DL42, which constitutively expressed LOS reactive with MAb 5G8 . This library was used to transform a second Hib strain (DL180) that normally does not express this LOS epitope, and a recombinant clone was identified that bound MAb 5G8 . Subcloning of different regions of the Hib DL42 DNA insert in this recombinant plasmid determined that a 1.9-kb EcoRI fragment, designated lex-2, was responsible for transforming Hib strain DL180 to reactivity with MAb 5G8 . Nucleotide sequence analysis revealed the presence of two contiguous open reading frames (ORFs) in lex-2, the first of which contained 18 tandem repeats of the nucleotide tetramer GCAA near its 5' end . Sequence analysis of PCR-derived products from MAb 5G8-reactive and -nonreactive Hib DL180 colonies established that 18 GCAA repeats were associated with expression of the LOS epitope that bound MAb 5G8 . Mutational analysis determined that a functional ORF 2 was essential for expression of the MAb 5G8-reactive LOS epitope . The nucleotide tetramer GCAA repeat present in ORF 1 was also detected in at least two different chromosomal regions in all Hib strains tested . The availability of the cloned lex-2 locus should facilitate future analysis of the complex regulatory mechanisms involved in expression of LOS epitopes by this pathogen.

Rev Prat, 1994 Oct 15, 44(16), 2157 - 62
{Treatment of bacterial meningitis in newborn infants and children}; Aujard Y et al.; Third generation cephalosporin as cefotaxime or ceftriaxone is the best first line treatment . Duration of treatment is 7 to 10 days in uncomplicated disease . Dexamethasone used very early--before or at the same time of the antibiotic injection--seems to decrease sensorial sequelae . Amikacin by IV route, decreases short term complications . For bacterial meningitis due to intermediate penicillin pneumococci, an increase in daily dose of beta-lactamin is recommended; for resistant pneumococci, vancomycin by continuous infusion and with large doses is used . Chemoprophylaxis by rifampicine is effective for both Meningococcus and Haemophilus . Haemophilus influenzae b vaccination will decrease systemic infection due to this pathogen . In newborns, morbidity is higher, due in part to brain abscesses . Therapeutic choice is not the same for materno-foetal and postnatal infection . Antibiotherapy duration is, at least, 15 days and 21 days for gram-negative bacteria.

Rev Prat, 1994 Oct 15, 44(16), 2152 - 5
{Contributions of experimental models to the physiopathology and treatment of bacterial meningitis}; Decazes JM; Access to the cerebrospinal fluid, which is the only objective reflection of the essential parametres, is very limited . Investigators have long tried to design an animal model . Presently, the experimental model of the newborn rat is most often used for studying pathogenic factors in haematogenous meningitis . In contrast, the rabbit model is more adapted to therapeutic investigation The main advances have been therapeutic and pathophysiologic . Good examples are the identification of optimum antibiotic levels in the cerebrospinal fluid, and the demonstration of the responsibility of mediators produced by the host in triggering the inflammation . The principle of corticosteroid treatment before induction of bacterial lysis by antibiotics in Haemophilus meningitis is a result of such work.

Rev Prat, 1994 Oct 15, 44(16), 2148 - 51
{Epidemiology of primary bacterial meningitis}; Hoen B; In industrialized countries, the incidence of community-acquired bacterial meningitis is between 5 and 10 cases/10(5) population/year . The highest age-specific attack rates are recorded between 0 and 2 years of age and can reach 100 cases/10(5) population/year or more in some countries . In this range of age, Streptococcus agalactiae, Listeria monocytogenes and Escherichia coli are responsible for meningitis in neonates whereas Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae cause meningitis in children older than 1 month . H . influenzae was the leading cause of bacterial meningitis in children but its incidence has declined since the introduction of routine childhood immunization with conjugate vaccines . N . meningitidis is the leading cause of meningitis in teenagers and young adults, whereas S . pneumoniae is responsible for most of meningitis in the elderly . Prognosis of bacterial meningitis mainly depends on the type of causative organism and on the age of onset . Detailed epidemiologic features of Haemophilus, meningococcal and pneumococcal meningitis are provided.

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