Haemophilus

Jpn J Antibiot, 1993 Jul, 46(7), 577 - 88
{A clinical study on cefditoren pivoxil granules in the pediatric field}; Mori A et al.; The clinical efficacy of cefditoren pivoxil (CDTR-PI, ME 1207) was evaluated in 45 patients with various infections . CDTR-PI was administered after meals at a dose of 3 mg/kg t.i.d . to most patients . The clinical efficacy rate was 95.3% . As side effects, diarrhea occurred in 2 patients . Cefditoren showed excellent antibacterial activities against Haemophilus influenzae, Streptococcus pyogenes and Streptococcus pneumoniae, and was more effective against Staphylococcus aureus than other cephems.

Antimicrob Agents Chemother, 1993 Jul, 37(7), 1552 - 5
In vitro susceptibilities of isolates of Haemophilus ducreyi from Thailand and the United States to currently recommended and newer agents for treatment of chancroid; Knapp JS et al.; We determined the in vitro susceptibilities of 54 isolates of Haemophilus ducreyi from Thailand (29 isolates) and San Francisco (25 isolates) to penicillin G, tetracycline, amoxicillin-clavulanic acid, ceftriaxone, cefixime, erythromycin, azithromycin, ciprofloxacin, ofloxacin, and trimethoprim-sulfamethoxazole . Isolates were susceptible to < or = 0.25 microgram of ceftriaxone per ml, < or less 0.5 microgram of cefixime per ml, < or = 0.125 microgram of ciprofloxacin per ml, and < or = 0.06 microgram of ofloxacin per ml . Erythromycin was active against all isolates (MIC for 90% of isolates tested, 0.25 microgram/ml), as was azithromycin (MIC, < or = micrograms/ml) . In contrast, all but one isolate were resistant to > or = 8.0 micrograms of tetracycline per ml, 11.1% of the isolates were resistant to and 40.9% of the isolates were resistant to trimethoprim-sulfamethoxazole (MIC, > or = 4/76 microgram/ml.)

An Esp Pediatr, 1993 Jul, 39(1), 42 - 5
{Neonatal conjunctivitis: microbiologic study and antibiotic sensitivity}; Martinez Ruiz MT et al.; We have analyzed retrospectively fifty conjunctival samples from infants less than one month of age affected with conjunctivitis . Of these samples, 84% had a positive bacterial culture, with the microorganisms isolated, in order of frequency, being: Staphylococcus epidermidis (14%), Staphylococcus aureus (14%), Streptococcus pneumoniae (12%), Haemophilus sp, Chlamydia and alpha-hemolytic Streptococcus (8%) . All of these showed a high sensitivity to most of the drugs tested, except to penicillin and its derivatives . Cefotaxime, ceftriaxone and ciprofloxacin showed the highest in vitro activities . Of the pharmacological ophthalmic preparations commercially available in our country, sulfonamides, chloramphenicol, rifampicin, erythromycin and tobramycin are the agents more active against the bacteria described above.

Pharmacotherapy, 1993 Jul-Aug, 13(4), 396 - 401
Institution-specific patterns of infection and Gram's stain as guides for empiric treatment of patients hospitalized with typical community-acquired pneumonia; Belliveau P et al.; STUDY OBJECTIVE . To determine the appropriateness of cefazolin as empiric treatment of typical, as opposed to atypical, bacterial community-acquired pneumonia at our institution . DESIGN . Combination of retrospective chart review and prospective determination of microbial susceptibilities and cefazolin-associated cost savings . SETTING . General acute-care referral hospital . PATIENTS . We evaluated the charts of patients discharged with a diagnosis of community-acquired pneumonia over a 10-year period . Gram's stains and culture results of sputum samples processed over 2 months were analyzed to determine the ability of the stains to predict positive Haemophilus influenzae cultures . The susceptibility and beta-lactamase status of clinical isolates of H . influenzae were determined . Cost savings of cefazolin as empiric treatment for community-acquired pneumonia were evaluated . MEASUREMENTS AND MAIN RESULTS . The frequency of H . influenzae pneumonia at our institution was 15% of the three major bacterial community-acquired pneumonias . Gram's stain was highly accurate in predicting the presence or absence of Haemophilus sp in sputum . Five patients had positive outcomes with cefazolin treatment despite being diagnosed with H . influenzae pneumonia . The organism isolates demonstrated intermediate sensitivity to cefazolin and 85% were beta-lactamase negative . Our program that encourages empiric use of cefazolin over cefuroxime for typical bacterial community-acquired pneumonia has allowed a modest projected annual cost savings of $24,000 . CONCLUSIONS . We concluded that when Gram's stain of sputum does not show Haemophilus sp in patients with typical bacterial community-acquired pneumonia, empiric treatment with cefazolin is appropriate and results in cost savings.

Diagn Microbiol Infect Dis, 1993 Jul, 17(1), 61 - 5
In vitro susceptibility test practices with Haemophilus influenzae among College of American Pathologists survey participants in the United States; Doern GV et al.; Questionnaire results from 5233 clinical microbiology laboratories participating in the College of American Pathologists (CAP) survey program in the United States were used to establish current standards of practice with respect to in vitro susceptibility testing of Haemophilus influenzae . The results of this CAP survey indicated that the recently developed National Committee for Clinical Laboratory Standards (NCCLS) guidelines for H . influenzae susceptibility tests have been widely adopted, particularly with regard to the medium used to perform susceptibility tests . Haemophilus test medium (HTM) is now the most commonly used medium and there exists a general level of satisfaction (approximately 80%) with medium performance . Specific methodologic recommendations of the NCCLS, however, are often not being followed, for example, length and atmosphere of incubation and means of preparing inocula . beta-Lactamase assays constitute a very commonly employed means of assessing ampicillin activity . Among susceptibility test methods, disk diffusion (82.2%) is much more commonly used compared with broth microdilution (17.8%) procedures . Data are provided regarding the most commonly tested antimicrobials as well as some of the problems encounted when using current NCCLS methods for susceptibility tests with H . influenzae . Finally, the CAP survey questionnaire revealed that many laboratories have applied HTM to susceptibility tests with other fastidious bacteria such as pathogenic Neisseria sp., streptococci, and Moraxella catarrhalis.

Eur J Pediatr, 1993 Jul, 152(7), 613 - 4
Guillain-Barré syndrome following immunisation with Haemophilus influenzae type b conjugate vaccine; Gervaix A et al.; The Guillain-Barre syndrome (GBS) is an immune-mediated disease often associated with viral or bacterial infections and with immunisation . IgM antibodies have been implicated as the main trigger event in GBS . So far, only four cases of GBS have been observed following immunisation with a conjugate vaccine against Haemophilus influenzae type b . We report another patient with GBS after this vaccination . We measured immunoglobulins against the H . influenzae type b polysaccharide (PRP) component of the vaccine . Surprisingly the anti-PRP IgM antibody level was markedly elevated (100 micrograms/ml) in the plasma of this patient . We speculate that an excessive anti-PRP IgM antibody response to the vaccine might be the cause of GBS.

J Clin Microbiol, 1993 Jul, 31(7), 1856 - 9
Identification of Actinobacillus actinomycetemcomitans by leukotoxin gene-specific hybridization and polymerase chain reaction assays; Tonjum T et al.; Eleven strains of Actinobacillus actinomycetemcomitans isolated from cases of systemic infections, local abscesses, and periodontitis were identified by genetic assays using the leukotoxin gene as the target . We have developed a polymerase chain reaction (PCR) assay, based on the leukotoxin structural gene of this pathogen, which clearly identified all tested strains of A . actinomycetemcomitans and separated them from the closely related Haemophilus aphrophilus as well as other bacterial species . Furthermore, DNA-DNA hybridization was performed with the cloned partial leukotoxin structural gene (lktA) as a probe, which again clearly distinguished A . actinomycetemcomitans from H . aphrophilus, parts of the normal oral flora, and species harboring RTX (repeats in toxin) family-related cytotoxins . The PCR fragment amplified from the leukotoxin structural gene gave results similar to those given by the cloned leukotoxin gene when used as a probe in hybridization experiments . The hybridization and PCR assays described here are fundamental improvements for the identification of A . actinomycetemcomitans.

Pediatr Infect Dis J, 1993 Jul, 12(7), 593 - 9
Vaccination with Haemophilus influenzae type b meningococcal protein conjugate vaccine reduces oropharyngeal carriage of Haemophilus influenzae type b among American Indian children; Takala AK et al.; The effect of Haemophilus influenzae type b (Hib) meningococcal protein conjugate vaccine (Hib-OMPC; Merck, Sharp & Dohme) on oropharyngeal (OP) carriage of Hib was evaluated in Navajo and Apache Indian children, who are known to be at high risk for invasive Hib disease . We obtained 1423 OP swabs at well child visits from 1321 children 3 months to 4 years of age: 293 of the swabs were obtained from children before the administration of any Hib-OMPC; 1119 were taken after the primary vaccination series; and 11 after the booster dose . Swabs were tested for the presence of Hib capsular polysaccharide antigen by enzyme-linked immunosorbent assay . Forty of 1423 swabs were positive for Hib . Among the 40 positive swabs 5 (13%) were obtained from children who had received Hib-OMPC vaccine appropriate for age at swabbing, compared with 500 of 1383 (36%) of negative swabs . Children who were OP carriers of Hib were older than noncarriers (mean age, 13 and 9 months, respectively) and a greater proportion of carriers (48%) had symptoms of respiratory infection at the time of swabbing than noncarriers (30%) . These variables were significantly related to increased risk of OP carriage of Hib when incorporated jointly in a logistic regression model: not vaccinated according to age (odds ratio 2.7, 95% confidence interval 1.00 to 7.05); increase of age in months (odds ratio 1.1, 95% confidence interval 1.02-1.10); and respiratory infection symptoms present (odds ratio 2.0, 95% confidence interval 1.06-3.77) . Thus besides preventing invasive Hib disease, appropriate vaccination with Hib-OMPC appears to reduce OP carriage of Hib.

Pediatr Infect Dis J, 1993 Jul, 12(7), 589 - 93
Carriage of Haemophilus influenzae type b in children after widespread vaccination with conjugate Haemophilus influenzae type b vaccines; Mohle-Boetani JC et al.; Rates of invasive Haemophilus influenzae type b (Hib) disease in children decreased very rapidly after licensure of Hib conjugate vaccines . A role for a vaccine-related reduction in nasopharyngeal carriage of Hib has been suggested . We studied oropharyngeal carriage of Hib and vaccination rates in a population of 2- to 5-year-old children in metropolitan Atlanta . Among 584 children 75% were vaccinated with an Hib conjugate vaccine, 17% had not been vaccinated and 8% had no vaccination records available . Forty-one percent of the children were colonized with H . influenzae . One child was colonized with Hib . Hib carriage (0.17%; upper 95% confidence interval boundary, 0.97%) was substantially lower than the estimates of Hib carriage from prior studies of children who had not received Hib conjugate vaccines . Our data are consistent with a decline in Hib carriage induced by widespread use of conjugate Hib vaccines, which may have contributed to the decline of Hib disease in United States children.

J Clin Invest, 1993 Jul, 92(1), 297 - 302
A structure-activity relationship for induction of meningeal inflammation by muramyl peptides; Burroughs M et al.; Components of bacterial peptidoglycans have potent biological activities, including adjuvant effects, cytotoxicity, and induction of sleep . Mixtures of peptidoglycan components also induce inflammation in the lung, subarachnoid space, and joint, but the structural requirements for activity are unknown . Using a rabbit model for meningitis, we determined the biological activities of 14 individual muramyl peptides constituting > 90% of the peptidoglycan of the gram-negative pediatric pathogen Haemophilus influenzae . Upon intracisternal inoculation, most of the muropeptides induced leukocytosis in cerebrospinal fluid (CSF), influx of protein into CSF, or brain edema, alone or in combination . The disaccharide-tetrapeptide, the major component of all gram-negative peptidoglycans, induced CSF leukocytosis and protein influx at doses as low as 0.4 microgram (0.42 nM) . Modification of the N-acetyl muramic acid or substitution of the alanine at position four in the peptide side chain decreased leukocytosis but enhanced brain edema . As the size of the muropeptide increased, the inflammatory activity decreased . Muropeptide carrying the diaminopimelyl-diaminopimelic acid cross-link specifically induced cytotoxic brain edema . These findings significantly expand the spectrum of biological activities of natural muramyl peptides and provide the basis for a structure-activity relationship for the inflammatory properties of bacterial muropeptides.

Am Rev Respir Dis, 1993 Jul, 148(1), 201 - 7
Haemophilus influenzae infection of human respiratory mucosa in low concentrations of antibiotics; Tsang KW et al.; We examined the effects of 0.25 and 0.5 minimal inhibitory concentrations (MIC) of amoxicillin, loracarbef, and ciprofloxacin on the interaction of a clinical isolate of nontypable Haemophilus influenzae (NTHi) with human adenoid organ culture . Adenoid tissue was embedded in agar so that only the mucosal surface was exposed . Minimum essential medium containing NTHi with or without antibiotics was added to the organ culture and incubated with 5% CO2 at 37 degrees C for 24 h . The organ cultures (n = 6) were assessed for several parameters by light microscopy (LM) and transmission electron microscopy (TEM) . Bacterial viable counts after 24 h were not significantly different in all organ cultures . Compared with uninfected controls at 24 h, infection with NTHi caused significant (p < 0.05) damage to epithelium as assessed by LM: reduced ciliary beat frequency (CBF), disruption of epithelium integrity, and reduced number of ciliated sites . TEM showed extrusion of cells from the epithelial surface, loss of cilia from ciliated cells, cytoplasmic blebbing, and mitochondrial damage . In the presence of 0.25 and 0.5 MIC of all three antibiotics, the mucosal damage was significantly less (p < 0.05) . We conclude that in the presence of sub-MIC levels of amoxicillin, loracarbef, and ciprofloxacin, NTHi infection causes less functional (CBF) and structural damage.

Avian Dis, 1993 Jul-Sep, 37(3), 673 - 9
Efficacy of norfloxacin nicotinate treatment of broiler breeders against Haemophilus paragallinarum; Lublin A et al.; The efficacy of the antimicrobial drug norfloxacin for treating infectious coryza was examined in 26-week-old male broiler breeders . Chickens were inoculated in the infraorbital sinus with the causal organism, Haemophilus paragallinarum . Four experimental groups were set up: control uninfected chickens, infected untreated chickens, and infected chickens treated for 5 days with either 20 mg norfloxacin/kg body weight or 40 mg norfloxacin/kg body weight . The first clinical signs were seen 24 hr postinfection . Of the observed clinical signs, sinus edema was ameliorated by the treatment, and the percentage of birds presenting sinus edema, sneezing, and increased lacrimation was significantly reduced after treatment . Clinical signs disappeared rapidly and were gone by the second day of treatment . The other signs disappeared gradually over 2 weeks after treatment began . There were no significant differences between the two dosage levels . H . paragallinarum was not reisolated from the infected infraorbital sinuses of birds treated with the higher dose of the drug, whereas the reisolation rate was 17% from those treated with the lower dose and 86% from the infected untreated birds.

J Clin Pathol, 1993 Jul, 46(7), 680 - 1
Terminal subculture of blood cultures using a multipoint inoculator device; Thickett KJ et al.; A multipoint inoculation method was used for the terminal subculture of blood cultures . This economical yet reliable technique successfully isolated important human pathogens such as Haemophilus influenzae from macroscopically negative blood cultures.

J Infect Dis, 1993 Jul, 168(1), 177 - 87
Molecular characterization of resistance plasmids in epidemiologically unrelated strains of multiresistant Haemophilus influenzae; Levy J et al.; Thirty-three epidemiologically unrelated strains of ampicillin-chloramphenicol-resistant isolates of Haemophilus influenzae (22 type b, 11 unencapsulated), isolated over 10 years in Belgium, were compared with 53 ampicillin-resistant chloramphenicol-susceptible isolates (22 type b, 31 unencapsulated) . All ampicillin-chloramphenicol-resistant and 76% of ampicillin-resistant chloramphenicol-susceptible strains were resistant to tetracycline, kanamycin, or both . Resistance to these antibiotics was specified by a 37- to 44-MDa conjugative plasmid . The genetic relatedness of these plasmids and of those in multiresistance strains from Spain was investigated . Plasmids specifying ampicillin-chloramphenicol-tetracycline-kanamycin resistance in Belgium or in Spain had highly related restriction fragment patterns . By homoduplex analysis, they had similar molecular organization and contained a structure identical to Tn10-TnCm, a transposon previously identified in chloramphenicol-tetracycline-resistant H . influenzae . Plasmids coding for different resistance phenotypes had less resemblance by restriction endonuclease analysis; however, study of heteroduplex molecules indicated they shared a high proportion of core sequences . These findings support the hypothesis of independent transposition events resulting in resistance plasmids of close molecular organization.

Rev Latinoam Microbiol, 1993 Jul-Sep, 35(3), 297 - 300
{Evaluation of a selective medium with dilutions for the isolation of Actinobacillus pleuropneumoniae and Haemophilus spp . in pigs}; Rosado-Vallado M et al.; The aim of the present research was to evaluate the efficiency of a method used to enhance the isolation of Actinobacillus pleuropneumoniae and Haemophilus spp . 134 samples of pneumonic lungs of swine were directly grown in blood agar medium, 120 of these samples were simultaneously processed by a dilution method inoculating then into a selective and enriched broth (1% poly-enriched, 5% yeast extract . 5 micrograms/ml bacitracin, 1 microgram/ml lincomycin and 1 microgram/ml crystal violet) . The dilution method proved to be more efficient than the direct one.

Rev Latinoam Microbiol, 1993 Jul-Sep, 35(3), 259 - 65
{Lack of foto reactivation of the Haemophilus influenzae transforming DNA mutated with near ultraviolet light (325-400nm)}; Alarcon-Hernandez E et al.; Three extracts from Saccharomyces cerevisiae were obtained by salting out with ammonium sulfate, these were I-G, EFRL-II-G and III-G . Fraction EFRL-II-G showed the highest photoreactivating activity on DNA str2000 irradiated with far UV light . However, the same fraction did not reactivate DNA str2000 previously inactivated by near UV irradiation . We think that the inactivation by near-UV was not due to photochemically-formed pyrimidine dimers . Decrease in spontaneous mutation frequency of cells transformed with DNA str2000 irradiated with near-UV light, was the same with the DNA treated with active or heat inactivated EFRL-II-G, therefore we may conclude that DNA lesions responsible for the effect are difference to pyrimidine dimers.

Eur J Epidemiol, 1993 Jul, 9(4), 353 - 60
Genomic DNA fingerprints and phenotypic characteristics of serotype B Haemophilus influenzae isolates from Italy; Mencarelli M et al.; Three different restriction enzymes (PstI, EcoRI, SspI) were used to analyze the total genomic DNA fingerprints of 52 Haemophilus influenzae type b (Hib) isolates collected between 1982 and 1992 from patients and carriers in central-northern Italy . The same isolates were also characterized by biotyping and antimicrobial agent susceptibility typing . In addition, 13 Hib reference strains from Sweden and the Netherlands were subjected to DNA fingerprinting and compared to Italian isolates . Both genotypic and phenotypic analysis revealed low variability among the Italian study isolates . Most were biotype I and all study isolates but one were susceptible to ampicillin, chloramphenicol, rifampin, third-generation cephalosporins and cotrimoxazole . Among the 52 Italian isolates, 3 distinct DNA patterns were identified, and 88.5% of study strains belonged to the same DNA group . There was sharing of the predominant DNA profile among isolates cultured in different years from different geographical areas and different invasive, respiratory and surface infections . However, another DNA pattern was only found in carrier isolates and in one surface infection isolate . Comparison by DNA fingerprinting showed that the majority of Italian isolates were closely related to most of the analyzed Swedish and Dutch reference strains, previously shown by other techniques to be predominant in those areas . This finding provides additional support for the hypothesis that there may be a dominant European Hib clone . The results show that DNA fingerprinting is a reliable method for Hib characterization and may be a useful additional epidemiological tool for this microorganism.

J Clin Microbiol, 1993 Jul, 31(7), 1952 - 4
N-acetyl-D-glucosamine medium improves recovery of Haemophilus influenzae from sputa of patients with cystic fibrosis; Moller LV et al.; A modified selective medium supplemented with N-acetyl-D-glucosamine (NAG), hemin, and NAD plus two cefsulodin disks, for primary isolation of nonencapsulated Haemophilus influenzae from sputum of patients with cystic fibrosis, is described . Isolation of H . influenzae from this medium, designated NAG medium, was compared with recovery by standard media and immunochemical detection of H . influenzae with monoclonal antibody 8BD9 . The H . influenzae recovery rate increased from 31% with standard media to 42% with NAG medium . H . influenzae was detected by immunoperoxidase staining in 54% of the sputum specimens . The results of this study demonstrate that NAG medium improves H . influenzae recovery, although immunoperoxidase staining is superior for detection of H . influenzae from sputum of cystic fibrosis patients.

J Biol Chem, 1993 Jun 5, 268(16), 11594 - 8
Composition of the peptidoglycan of Haemophilus influenzae; Burroughs MH et al.; The composition of the peptidoglycan of Haemophilus influenzae was determined by analyzing glycopeptides generated by M1 muramidase hydrolysis using high pressure liquid chromatography, fast atom bombardment mass spectrometry, and fast atom bombardment collisionally activated dissociation tandem mass spectrometry, and amino acid analysis . The structures of 17 glycopeptides, representing 96% of the total peptidoglycan, were ascertained . Fifteen glycopeptides resembled species described for Escherichia coli peptidoglycan (Glauner, B., and Schwarz, U . (1983) The Target of Penicillin (Hackenbeck, R., ed), Walter de Gruyter, Berlin pp . 29-34) as compared with 9 in common with Bordetella pertussis (Tuomanen, E., Schwartz, J., Sande, S., Light, K., and Gage, D . (1989) J . Biol . Chem . 264, 11093-11098) . Substitutions for L-alanine in the fourth position of the stem peptide included glycine, aspartic acid, and serine . The peptidoglycan was 27% cross-linked, 2% of which formed between diaminopimelic acid residues . No species was identified containing lysyl-arginine residues characteristic of lipoprotein . The peptidoglycan of non-beta-lactamase-mediated antibiotic-resistant H . influenzae differed from that of sensitive strains by an increase in the amount of disaccharide tripeptides and a decrease in 1,6-anhydro dimers . Both changes were transformable properties that changed in a stepwise fashion in parallel with the degree of antibiotic resistance.

Bol Med Hosp Infant Mex, 1993 Jun, 50(6), 415 - 21
{The impact of Haemophilus influenzae infections on Mexican children}; Villasenor-Sierra A et al.; A review of Haemophilus influenzae (Hi) infections in Mexico over the past 32 years was conducted . The proportion of Hi isolates in relation to positive cultures for distinct diseases was distributed as follows for meningitis (9-69%) and for pneumonia with empyema (6-28%) . There was no difference in the proportion of Hi isolation between under developed countries and the United States . In other diseases such as septic arthritis, epiglottitis, acute otitis media, acute maxillary sinusitis and in the nasopharyngeal carrier state, the information was too limited . The incidence of Hib invasive disease has been almost eliminated in some areas of the world related to the use of Hib conjugated vaccine . It is imperative for the practitioner to be aware of the advantages of Hib vaccine in infancy.

J Clin Invest, 1993 Jun, 91(6), 2734 - 43
Restricted immunoglobulin VH usage and VDJ combinations in the human response to Haemophilus influenzae type b capsular polysaccharide . Nucleotide sequences of monospecific anti-Haemophilus antibodies and polyspecific antibodies cross-reacting with self antigens; Adderson EE et al.; To examine the human antibody repertoire generated against a biologically significant antigen we have obtained sequences of heavy chain variable region genes (IgVH) from 15 monoclonal antibodies specific for the capsular polysaccharide of Haemophilus influenzae type b (Hib PS) . All VH segments are members of the VH3 family and 9 of 15 are members of the smaller VH3b subfamily . Restriction is evident by the shared use of certain VDJ joints in independent hybridomas from different subjects . Two hybridomas generated from the same subject demonstrate identical heavy chain variable region gene sequences but differ in isotype and rearrange alternative light chain variable region genes (IgVL), suggesting that in a normal immune response, a single pre-B cell clone may use different light chain rearrangements and give rise to progeny capable of reacting with antigen . Using a polymerase chain reaction assay optimized to detect base pair differences among VH genes we demonstrate that at least a portion of expressed anti-Hib PS VH genes have undergone somatic mutation . Anti-Hib PS heavy chain genes are homologous to VH segments encoding autoantibodies and two hybridomas secrete anti-Hib PS antibody that cross-reacts with self antigens (double-stranded DNA and single-stranded DNA) . Comparison of VH regions of self-reactive and monospecific anti-Hib PS Ab demonstrates no consistent structural feature correlating with fine antigen specificity . These data demonstrate significant restriction in VH usage and VDJ recombination in the anti-Hib PS response and confirm that autoantibodies may be elicited during normal immune responses.

Infect Immun, 1993 Jun, 61(6), 2653 - 61
Immunogenicity of overlapping synthetic peptides covering the entire sequence of Haemophilus influenzae type b outer membrane protein P2; Chong P et al.; Haemophilus influenzae type b is a major cause of bacterial meningitis in young children . Antibodies against the outer membrane protein P2 are protective in the infant rat model of bacteremia . To identify conserved, surface-exposed, and protective epitopes of P2, 17 overlapping peptides covering the entire sequence of the protein were synthesized . Antisera from mice, guinea pigs, and rabbits raised against chromatographically purified P2 were tested for their reactivities to the peptides by enzyme-linked immunosorbent assays (ELISA) . Three major linear immunodominant B-cell epitopes were mapped to residues 53 to 81, 241 to 265, and 314 to 341 of mature P2 . Human convalescent-phase antisera also reacted strongly with these three epitopes . Rabbit antisera against all peptide-keyhole limpet hemocyanin conjugates except two peptides containing residues 8 to 19 and 302 to 319 recognized the corresponding peptides in ELISA and reacted with P2 on immunoblots . Immunization with all unconjugated peptides, except the 19 N-terminal residues, induced very strong peptide-specific antibody responses, and these antisera reacted with P2 on immunoblots . Rabbit antisera raised against peptides corresponding to residues 1 to 14, 125 to 150, 193 to 219, and 241 to 319 also recognized P2 purified from H . influenzae nontypeable isolates . Identification of these immunodominant B-cell epitopes and conserved regions is a first step toward the rational design of a universal H . influenzae vaccine.

Infect Immun, 1993 Jun, 61(6), 2558 - 62
Specific antibody to Haemophilus somnus in the bovine uterus following intramuscular immunization; Butt BM et al.; Sources of anti-Haemophilus somnus antibody in bovine uterine secretions following intramuscular immunization and subsequent intrauterine inoculation of killed H . somnus were investigated . Holstein cattle (n = 21) were immunized with a 270-kDa outer membrane protein from H . somnus (omp-270) by intramuscular injection . At estrus, the cattle were given an intrauterine inoculum of a heat-killed suspension of a homologous strain of H . somnus containing omp-270 (n = 7), a heterologous strain of H . somnus lacking omp-270 (n = 7), or phosphate-buffered saline (n = 7) . Uterine secretions were sampled by saline lavage immediately prior to inoculation and at 6, 24, 48, 72, 96, and 120 h after inoculation . Immunoglobulin G subclass I (IgG1) and IgG2 antibody specific for omp-270 were detectable in estrous uterine secretions of all systemically immunized cattle from which an adequate sample was obtained . IgM antibody specific for omp-270 was detected in serum following immunization but was not consistently detected in the uterine secretions of any animal . IgA antibody specific for omp-270 was not detectable in either serum or uterine secretions following immunization or intrauterine inoculation . Ratios of antibody to immunoglobulin and ratios of immunoglobulin to albumin in serum and uterine secretions indicated that about half the IgG1 and essentially all the IgG2 in secretions originated in the serum . Relative titers of IgG1 and IgG2 omp-270-specific antibodies in the uterine lumen and serum gave no evidence for selective transport of either subclass from serum into local secretions . Neither heterologous nor homologous intrauterine inocula detectably altered the serum contribution to antibody in uterine secretions within the sampling period . On the basis of these results, development of a systemic IgG2 antibody response may provide the basis for local immunological protection in the bovine reproductive tract.

Microb Pathog, 1993 Jun, 14(6), 451 - 62
Genetic analysis of the diversity in outer membrane protein P2 of non-encapsulated Haemophilus influenzae; Duim B et al.; The molecular basis for the diversity of the major outer membrane protein (MOMP) P2 of non-encapsulated Haemophilus influenzae was analyzed by direct sequencing of fragments of the P2 genes, obtained by the polymerase chain reaction . Genetically divergent H . influenzae strains were isolated from patients with otitis media and from infected patients with chronic obstructive pulmonary disease (COPD) . The nucleotide sequences of these P2 genes were determined and compared with P2 gene sequences of three non-encapsulated strains and with the P2 gene of encapsulated H . influenzae type b . Variation in the nucleotide sequence of the P2 genes of non-encapsulated H . influenzae was localized in eight distinct regions which were interchanged with relatively conserved regions . Regions 2, 4, 5 and 8 were found to be hypervariable, since they were characterized by multiple deletions or substitutions of nucleotides . According to the proposed structure of MOMP P2 the variable regions were localized in eight loop structures exposed at the outside of the outer membrane . Loops 2, 4, 5 and 8 were hypervariable in all isolates whereas loop 6 varied only in isolates from COPD patients with persistent infections.

Microb Pathog, 1993 Jun, 14(6), 417 - 31
Evidence of Haemophilus ducreyi adherence to and cytotoxin destruction of human epithelial cells; Lagergard T et al.; The adherence of ten different Haemophilus ducreyi strains to cultured human epithelial cells and the subsequent destruction of these cells was investigated in vitro using HEp-2 and HeLa cells . Bacterial adherence was measured with two assays, one employing viable bacteria and the other radiolabeled bacteria . In addition, the capacity of H . ducreyi to invade/penetrate the HEp-2 cells was examined . Differential interference contrast and transmission electron microscopy techniques were also used . In both cell lines, all ten strains of H . ducreyi manifested substantial adherence (the rates being 4-20% of the inoculum), irrespective of whether the bacteria were cultivated on solid or liquid media . Bacterial adherence reached a peak after about 2-3 h of incubation, though it was already manifest after only 15 min, a finding suggesting constitutive rather than inducible properties of H . ducreyi adhesins to be involved . The adherence capacity was diminished, but not totally abolished, when bacteria were heat-treated at 100 degrees C for 30 min, indicating the adhesins to be fairly stable . On the other hand, treatment of HEp-2 cells with methanol, glutaraldehyde and emetine dichloride significantly reduced the adherence, indicating viable eukaryotic cells with native surface structures to be involved in bacterial adherence . This capacity of H . ducreyi to adhere to HEp-2 cells was confirmed both by electron microscopy and by differential interference microscopy . Some adherent bacteria were also capable of penetrating epithelial cells, as observed with an invasion assay and confirmed by transmission electron microscopy . Further incubation of the cell monolayers with the ten strains resulted in the cell-death and total damage of monolayers for seven cytotoxin-producing strains, indicating cytotoxin action to be responsible for the destruction of the monolayer . All strains manifested capacity to survive and multiply on the cell monolayer . We propose the first step in the pathogenesis of chancroid to be the adherence of bacteria to epithelial cells, followed by the action of cytotoxin and further bacterial proliferation . This sequence of events is suggested to result in the production of genital ulcers by H . ducreyi organisms.

J Antimicrob Chemother, 1993 Jun, 31 Suppl E, 39 - 50
Selection of dose regimens of azithromycin ; Foulds G et al.; The unique pharmacokinetics of azithromycin are characterized by high, sustained tissue concentrations . The concentrations of azithromycin were predicted, following various multiple dose regimens, from concentrations in tonsillar, prostatic, and uterine tissues following single oral doses . Following a five-day treatment regimen (500 mg on day 1, followed by 250 mg on days 2-5), or a three-day regimen (500 mg daily for three days), concentrations of azithromycin in tonsillar tissue, representative of respiratory tract tissues, will continuously be greater than the MICs for key target pathogens (Streptococcus pyogenes, Haemophilus influenzae, Staphylococcus aureus) in infections of the respiratory tract for up to 10 days . Since tissue concentrations above the MICs for infecting organisms were correlated with efficacy in animal models of infection, short treatment regimens consisting of once-daily oral administration of azithromycin should be effective in the treatment of a variety of infections . A single 1 g oral dose will provide concentrations in the uterus and prostate, representing urogenital tissues, above the MIC for Chlamydia trachomatis for approximately 10 days . Thus, this regimen should be effective in the treatment of chlamydial infections of the genital tract.

J Antimicrob Chemother, 1993 Jun, 31 Suppl E, 163 - 9
The efficacy and tolerance of a three-day course of azithromycin in the treatment of community-acquired pneumonia; Myburgh J et al.; The clinical efficacy and tolerance of a three-day course of azithromycin was evaluated in patients with community-acquired pneumonia in an open, non-comparative pilot study . Sixty-six patients with clinical and radiological findings of pneumonia were treated with a total dose of 1.5 g azithromycin (500 mg once-daily for three days) . Of these 66 patients, 40 were evaluable clinically and microbiologically . Of the remaining 26 patients, 22 had no organisms isolated at baseline, and could only be evaluated clinically; two patients were lost to follow-up; and two patients were protocol violators . Of the 40 patients in whom aetiological agents were identified, 39 (98%) had a satisfactory clinical response (34 cured, five improved), including all eight patients diagnosed as having Legionella pneumophila pneumonia on the basis of serology . One patient with recurrent Haemophilus influenzae infection on day 8 was considered a failure . Total severity score for overall signs and symptoms was reduced significantly from a baseline level by day 2 (P = 0.0001) . Bacteriological eradication was achieved in 32 of 33 (97%) isolates including 27 of 27 Streptococcus pneumoniae, the most frequently isolated pathogen . All six patients with pneumococcal bacteraemia were cured clinically by day 14, and blood cultures were negative for four of these patients within 48 h . Treatment-related side effects were reported in 4 of 66 (6%) patients, but were all mild . Laboratory abnormalities were observed in 5 of 62 (8%) patients: elevated liver enzymes (2), elevated creatine levels (1), haematological test abnormalities (2), including one patient with severe eosinophilia.(ABSTRACT TRUNCATED AT 250 WORDS)

J Antimicrob Chemother, 1993 Jun, 31 Suppl E, 147 - 52
A single-blind comparison of three-day azithromycin and ten-day co-amoxiclav treatment of acute lower respiratory tract infections; Hoepelman AI et al.; The efficacy and safety of a three-day regimen of azithromycin (500 mg od) and a ten-day regimen of co-amoxiclav (625 mg tid) were compared in a single-blind study in 99 patients with acute lower respiratory tract infections . Of these, 70 (71%) suffered an infective exacerbation of their chronic obstructive pulmonary disease . Nine patients had pneumonia and 19 purulent bronchitis . Treatment success, defined as cure or improvement, occurred in 43 of 48 (90%) patients in the azithromycin group, compared with 45 of 51 (88%) patients in the co-amoxiclav group . The most common isolated pathogens were Haemophilus influenzae (25 cases; MIC range of azithromycin (A) < or = 0.06-4 mg/L; for co-amoxiclav (CA) 0.25-4 mg/L; Streptococcus pneumoniae (10 cases; A: < or = 0.06- > 128; CA: < or = 0.06); and Moraxella catarrhalis (four cases; A: < or = 0.06; CA: < or = 0.06-0.25) . Microbiological response rates were comparable in the two groups . In 5% of patients, serological evidence for virus or atypical pathogens was found . Thirteen (26%) patients treated with co-amoxiclav had gastrointestinal complaints (seven with diarrhoea), compared with five (10%) treated with azithromycin (P = 0.09) . Additional complaints occurred in three patients treated with co-amoxiclav and in one patient treated with azithromycin . It was concluded that a three-day regimen of azithromycin was as effective, clinically and microbiologically, as a ten-day regimen of co-amoxiclav in the treatment of acute lower respiratory tract infections.

Infect Immun, 1993 Jun, 61(6), 2419 - 24
Inhibition of human neutrophil migration in vitro by low-molecular-mass products of nontypeable Haemophilus influenzae; Cundell DR et al.; Nontypeable Haemophilus influenzae commonly causes infections in the lower and upper respiratory tract, although the mechanisms of its colonization and persistence in the airways are unclear . Culture filtrates from six clinical isolates of this bacterium were assessed for their abilities to influence neutrophil function in vitro . Each culture filtrate was assessed on six separate occasions with neutrophils obtained from six different donors . During the log and early stationary phases of growth (0 to 18 h), culture filtrates contained primarily neutrophil chemokinetic activity but no activity affecting neutrophil migration toward the chemotactic factors N-formyl-L-methionyl-L-leucyl-L-phenylalanine and leukotriene B4 . In contrast, filtrates obtained after 24 h of culture contained factors which inhibited neutrophil migration toward both of these chemotactic factors . This chemotaxis-inhibitory activity persisted between 24 and 72 h of bacterial culture, and it was not associated with the presence of either chemotactic or chemokinetic activity as assessed by checkerboard analysis . Gel filtration of pooled 72-h filtrates yielded three major peaks of chemotaxis-inhibitory activity . Endotoxin was present together with two other low-molecular-mass hydrophobic factors of approximately 8 and 2 kDa . These low-molecular-mass factors are chloroform insoluble and heat stable, and they are inactivated by protease, periodate, and diborane reduction . Activity was completely retained on a wheat germ agglutinin column, and it could be eluted with N-acetyl-D-glucosamine . These data suggest that inhibitory activity is associated with N-acetyl-D-glucosamine-containing glycopeptides, possibly derived from the bacterial cell wall . The production of these compounds may contribute to the persistence of this bacterium in vivo by inhibiting neutrophil chemotaxis in the microenvironment of the respiratory mucosa.

Zentralbl Bakteriol, 1993 Jun, 279(1), 83 - 91
Genetic analysis of Actinobacillus pleuropneumoniae, and comparison with Haemophilus spp . Taxon "minor group" and Taxon C; Hampson DJ et al.; The genetic diversity among 52 field isolates, mainly from Australia, and 15 reference strains of Actinobacillus pleuropneumoniae was examined using multilocus enzyme electrophoresis . Thirty three electrophoretic types (ETs) were recognised, with a mean genetic diversity per locus of 0.312 . Australian strains of serovars 1, 2, 5 and 7 belonged to the same clonal lines as strains of these serovars in other countries, but distinct clones of serovars 3, 7, 11 and 12 were also identified . The type strains of serovars 1, 9 and 11 were placed in the same ET . Strains of A . pleuropneumoniae biovar 2 were closely related to biovar 1 strains . Twenty three isolates which did not react with the typing sera or could not be assigned to a single serovar were divided into seven clonal groups . Five strains of Haemophilus sp . Taxon "minor group" which were included in the study were distinct from A . pleuropneumoniae, and were diverse, being divided into at least two major genetic groupings . Two strains of Haemophilus sp . Taxon C were placed in another distinct ET.

Zentralbl Bakteriol, 1993 Jun, 279(1), 27 - 34
Ecology and significance of Pasteurellaceae in man--an update; Frederiksen W; Within the last decade new knowledge has emerged concerning the significance of Pasteurellaceae in man; the classification has undergone some changes, and new taxa were described . Haemophilus influenzae serotype b was shown to have a clonal distribution that is related to demographic patterns of the human host . Brazilian purpuric fever is caused by a special clone of Haemophilus aegyptius . H . influenzae biotype IV seems to be a genital pathogen, and may deserve species rank . New Pasteurella species have been described, that occur in well known pathological foci in man, e.g . bite wounds . Toxigenic P . multocida may occur in man also; the significance of toxigenicity in man is not known . The real actinobacilli of man, A . ureae and A . hominis are still very rarely reported . In order to avoid wrong epidemiological conclusions, correct diagnosis is emphasized.

Zentralbl Bakteriol, 1993 Jun, 279(1), 114 - 24
Prevalence and biochemical properties of V factor-dependent Pasteurellaceae from rodents; Nicklas W et al.; Organs of 1436 rats and 2839 mice were monitored for V-factor dependent Pasteurellaceae . Such bacteria were isolated from 21.2% of rats and from 2.4% of mice, respectively . They were most frequently cultured from the deep respiratory tract (lungs and trachea) . In addition, they were found in the nasal cavity and on mucous membranes of the genital and the intestinal tract . 35 phenotypical criteria were determined for 429 isolates . Based on these data, groups of bacteria showing similar biochemical properties were formed using exploratory statistical methods (principal qualitative analysis) . The majority of 333 isolates is represented in a rather homogenous group which has some characteristics in common with the Haemophilus parainfluenzae complex . The remaining isolates consist of several groups . It was shown by others that some of these bacteria are closely related to the yet unnamed Taxon B which forms a genus-like cluster together with Pasteurella pneumotropica type Jawetz.

Mil Med, 1993 Jun, 158(6), 371 - 3
Immunization status of a military dependent population; Lopreiato JO et al.; The immunization status of active duty pediatric dependents served by the National Naval Medical Center was surveyed to estimate the degree to which this group was in compliance with immunization requirements . Four hundred sixteen patients who presented consecutively to a pediatric acute care clinic had their medical and immunization records screened . Ten percent of patients did not have complete records of immunization . Of the 375 patients remaining, 52 (13.9%) were deficient in one or more required immunizations based on their current age . The highest rates of delay were seen for the Haemophilus influenza vaccine followed by measles, mumps, rubella, and diphtheria, tetanus, and pertussis . The most common reason for missing immunizations was parental unfamiliarity with the recommended schedule . This study suggests that a significant number of dependents in our catchment area were delayed in immunization and that accurate record keeping and patient education about immunizations needs to be improved.

Mol Microbiol, 1993 Jun, 8(6), 1135 - 43
The region of human transferrin involved in binding to bacterial transferrin receptors is localized in the C-lobe; Alcantara J et al.; Iron-saturated human transferrin was digested with either chymotrypsin or trypsin to produce C-lobe and N-lobe protein fragments . Individual protein fragments were purified by a combination of gel filtration and Concanavalin A affinity chromatographic procedures . The C-lobe and N-lobe fragments of human transferrin were then used in binding assays to assess their ability in binding to the bacterial transferrin receptors . Competitive binding assays demonstrated that the C-lobe fragment of human transferrin binds as well as intact human transferrin to bacterial transferrin receptors from Neisseria meningitidis, Neisseria gonorrhoeae and Haemophilus influenzae . Using isogenic mutants of N . meningitidis deficient in either of the transferrin-binding proteins (Tbps), we demonstrated that both transferrin-binding proteins were able to bind to the C-lobe fragment of human transferrin.

J Antimicrob Chemother, 1993 Jun, 31(6), 949 - 61
Loracarbef versus doxycycline in the treatment of acute bacterial maxillary sinusitis . Scandinavian Study Group; Effects of recombinant GM-CSF and IgA opsonisation on neutrophil phagocytosis of latex beads coated with P6 outer membrane protein from Haemophilus influenzae; Lung Immunobiochemical Research Laboratory, General Hospital, Birmingham, UKBACKGROUND--IgA is the major antibody class in mucosal secretions, yet its biological functions remain poorly understood and its role as an opsonin for neutrophils has been the subject of controversy . It has been reported that treatment of neutrophils with granulocyte-macrophage colony stimulating factor (GM-CSF) induces the cells to phagocytose particles opsonised with IgA . A study was performed to investigate the effects of GM-CSF and IgA opsonisation on the ability of human neutrophils to recognise and phagocytose latex beads coated with the P6 outer membrane protein of Haemophilus influenzae . METHODS--Human neutrophils with and without preincubation with 100 pmol/l GM-CSF, were incubated with non-opsonised P6-coated latex beads or beads opsonised with IgA purified from the blood of a bronchiectatic patient with high titres of IgA anti-P6 . Phagocytosis was measured by counting internalised beads during microscopic examination . RESULTS--The phagocytosis of IgA opsonised beads by untreated neutrophils (mean (SE) 2.1 (0.43) beads/cell) was significantly greater than that of non-opsonised beads (mean (SE) 1.3 (0.30) beads/cell) . Treatment of neutrophils with GM-CSF resulted in increased phagocytosis of non-opsonised beads (mean (SE) 2.1 (0.39) beads/cell) but opsonisation with IgA increased this further (mean (SE) 3.4 (0.53) beads/cell) . CONCLUSIONS--Human neutrophils recognise and phagocytose non-opsonised particles coated with bacterial antigen . Antibodies of the IgA isotype opsonise for neutrophil phagocytosis of particles coated with bacterial antigen but this behaviour is enhanced, in an additive fashion, by treatment of the cells with GM-CSF . The results suggest that IgA and GM-CSF are important cofactors for neutrophil recognition and elimination of bacterial pathogens.

Pediatr Infect Dis J, 1993 Jun, 12(6), 484 - 92
Comparative immunogenicity of four Haemophilus influenzae type b conjugate vaccines in Alaska Native infants; Bulkow LR et al.; We compared the immunogenicity of the four available Haemophilus influenzae type b (Hib) conjugate vaccines in Alaska Native infants . Three of the vaccines, Hib oligosaccharide-CRM197 (HbOC), polyribosylribitol phosphate-diphtheria toxoid (PRP-D) and polyribosylribitol phosphate-tetanus toxoid (PRP-T), were given at 2, 4 and 6 months of age, and the PRP Neisseria meningitidis outer membrane protein (PRP-OMP) conjugate vaccine was given at 2 and 4 months of age . Enrollment was largely sequential by vaccine availability beginning with HbOC and ending with PRP-T . A total of 225 infants completed the full vaccination series . Groups of infants receiving the different vaccines did not differ significantly by sex, ethnicity, degree Alaska Native or age at vaccination . The only vaccine that induced a response with the first 2-month dose was PRP-OMP; 91% of infants had > or = 0.15 micrograms/ml and 57% had > or = 1.0 microgram/ml of anti-PRP antibody by 4 months of age . After two doses it also remained the most immunogenic . After the full three vaccine series, trials that requires cough of 21 days is excessively restrictive.

Pediatr Infect Dis J, 1993 Jun, 12(6), 478 - 84
Haemophilus influenzae type b carriage and immunity four years after receiving the Haemophilus influenzae oligosaccharide-CRM197 (HbOC) conjugate vaccine; Barbour ML et al.; Late in 1991, before the implementation of a national immunization program against Haemophilus influenzae type b (Hib) in the United Kingdom, we performed a 4-year follow-up of 120 children who in 1987 had been enrolled in an immunogenicity trial in which 60 of them (vaccinees) received an Hib conjugate vaccine (HbOC) at the same time as diphtheria-tetanus toxoid-pertussis vaccine at the ages of 3, 5 and 9 months . Sixty others (controls) received only diphtheria-tetanus toxoid-pertussis vaccine at the same ages and were not subsequently immunized against Hib . We investigated Hib pharyngeal colonization using the antiserum agar method and the concentrations of serum IgG antibody to the type b capsule by enzyme-linked immunosorbent assay . At 4 years of age the Hib colonization rates in vaccinees and controls were 8% (5 of 60) and 5% (3 of 60), respectively . The children colonized with Hib had greater serum anti-capsular IgG concentrations than did noncolonized children (P < 0.001), and colonized vaccinees tended to have higher concentrations than colonized controls (P = 0.053) . Regardless of Hib colonization status vaccinees had greater antibody concentrations than controls (P < 0.001) . Forty-nine percent of vaccinees had an antibody concentration > 1 microgram/ml . There was an inverse relationship between the Hib colony count on culture and the serum IgG concentration . These data indicate that the increase in serum antibody concentration after immunization with an Hib conjugate vaccine is sustained and that immunization primes for a booster response on exposure to Hib . There may be a relationship between previous Hib conjugate immunization and the density of Hib colonization in children.

Pediatr Infect Dis J, 1993 Jun, 12(6), 466 - 73
Antimicrobial treatment of occult bacteremia: a multicenter cooperative study; Bass JW et al.; This prospective multicenter study was conducted to define more clearly clinical and laboratory criteria that predict a strong probability of occult bacteremia and to evaluate the effect of empiric broad spectrum antimicrobial treatment of these children . Children 3 to 36 months old with fever > or = 40 degrees C (104 degrees F) or, > or = 39.5 degrees C (103 degrees F) with white blood cells (WBC) > or = 15 x 10(9)/liter, and no focus of infection had blood cultures obtained and were randomized to treatment with oral amoxicillin/potassium clavulanate or intramuscular ceftriaxone . Sixty of 519 (11.6%) study patients had positive blood cultures: Streptococcus pneumoniae, 51; Haemophilus influenzae b, 6; Neisseria meningitidis, 2; and Group B Streptococcus, 1 . Subgroups of high risk were identified as fever > or = 39.5 degrees C and WBC > or = 15 x 10(9)/liter, 55 of 331 or 16.6% positive with increasing incidence of positive culture with increasing increments of degrees of leukocytosis to WBC > or = 30 x 10(9)/liter where 9 of 21 or 42.9% were positive . Subgroups of significantly lower risk were identified as fever > or = 39.5 degrees C and WBC < 15 x 10(9)/liter, 5 of 182 or 2.7% positive and those with WBC < 10 x 10(9)/liter, 0 of 99 or 0.0% positive . Children with positive cultures who received ceftriaxone were nearly all afebrile after 24 hours whereas a significant number who received amoxicillin/potassium clavulanate remained febrile . In the 459 culture-negative children more amoxicillin/potassium clavulanate-treated children developed diarrhea and had less improvement in clinical scores after 24 hours than ceftriaxone-treated children.(ABSTRACT TRUNCATED AT 250 WORDS)

Aust Fam Physician, 1993 Jun, 22(6), 1015 - 7, 1020-1
Haemophilus influenzae type b . Conjugate vaccines for use in infants and children; Hanna JN et al.; Haemophilus influenzae type b (Hib) is a bacterial pathogen that causes serious, sometimes fatal, infections primarily in young children, especially in the second 6 months of life . Immunisation of children against Hib is now an important issue and four conjugate Hib vaccines have become available . The various vaccines, and their characteristics are documented in this paper.

Kansenshogaku Zasshi, 1993 Jun, 67(6), 574 - 83
{Efficacy of fibronectin on opsonic activity by alveolar macrophage and experimental rat pneumonia}; Yoshida T; The opsonic activity of plasma fibronectin (FN) by rat alveolar macrophage (AM) was examined, and the in vivo effect of FN in Staphylococcus aureus (S . aureus) experimental rat pneumonia was evaluated . The chemiluminescence response of AM was enhanced by the presence of FN (300 micrograms/ml) in S . aureus and Streptococcus pneumoniae, but was not enhanced in gram-negative rods (Haemophilus influenzae, Branhamella catarrhalis, Pseudomonas aeruginosa) . FN (300 micrograms/ml) promoted the phagocytosis of S . aureus by AM, but did not promote the bactericidal activity of that by AM . In the experimental rat pneumonia with S . aureus inoculation, plasma FN concentration decreased with time, but increased by the administration of FN (1 mg) . The number of bacteria in the lung, peripheral white blood cell and BAL fluid cell also decreased by the administration of FN . Furthermore, FN was significantly improved on inflammatory findings of rat lung tissue 24 hours after inoculation with S . aureus . These results suggest that FN plays an important role as an opsonic by alveolar macrophage, and that FN has utility for clinical trials in patients with pneumonia.

Arch Dis Child, 1993 Jun, 68(6), 763 - 7
Epidemiology of bacterial meningitis; Fortnum HM et al.; This 10 year retrospective study of all causes of bacterial meningitis for children resident in Nottingham District Health Authority area reports an annual incidence rate per 100,000 children aged 0-16 years of 16.0 (95% confidence interval 14.0 to 18.1) . There was a steady increase in incidence from 9.6/100,000 in 1980 to 24.3/100,000 in 1989 . This was mainly due to an increase in the incidence of meningococcal infections in the age group 1 month to 5 years . Incidence rates varied with age being: 37.2/100,000 (25.9 to 53.5) for 0-28 days of age, 115.5/100,000 (93.9 to 141.9) for 1-11 months of age, 28.5/100,000 (23.1 to 35.3) for 12-59 months of age, and 2.8/100,000 (1.9 to 4.1) for 5-16 years of age . Overall annual mortality incidence per 100,000 was 1.8 (1.2 to 2.8) . For the different age groups this was: 10.1 (4.8 to 21.1) for 0-28 days, 11.5 (6.0 to 22.2) for 1-11 months, 1.0 (0.3 to 3.1) for 12-59 months, and 0.4 (0.1 to 1.2) for 5-16 years of age . There were interactions between the type of meningitis and the year of the infection on the mortality rate . Mortality decreased in those with infections caused by bacteria other than Neisseria meningitidis and Haemophilus influenzae.

Onderstepoort J Vet Res, 1993 Jun, 60(2), 147 - 52
Plasmid-encoded NAD independence in some South African isolates of Haemophilus paragallinarum; Bragg RR et al.; Atypical Haemophilus paragallinarum have been isolated from both laying hens and broilers suffering from typical symptoms of infectious coryza in South Africa . Re-inoculation of these bacteria into SPF chickens resulted in similar pathology . The bacteria could be successfully re-isolated from the experimentally infected chickens . Four of the isolates from layers and 3 of those from broilers were found to be closely related to H . paragallinarum serotype A (0083 strain) when tested by the use of a panel of locally developed monoclonal antibodies in the enzyme linked immunosorbent assay (ELISA) . A total of 15 isolates from layers and 19 from broilers were found to be more typical of previously collected South African field isolates of H . paragallinarum . A 3rd group, consisting of 5 isolates from layers and 15 from broilers, showed no reaction with the panel of monoclonal antibodies . All the isolates were regarded as atypical because they no longer required V factor (NAD) for growth, whereas strain 0083 and previously collected field isolates M 85 and SB 86 did require it . Crude plasmid extractions from an isolate serologically related to 0083 was used to convert reference strains of H . paragallinarum into NAD-independent isolates, thus indicating that NAD independence is carried on a plasmid.

Clin Infect Dis, 1993 Jun, 16 Suppl 4, S292 - 8
Bacteriologic findings in peritonsillar abscesses in young adults; Jousimies-Somer H et al.; Aspirated pus samples from 124 patients with peritonsillar abscess were cultured quantitatively for aerobes and anaerobes . A total of 98% of the samples yielded bacteria . Of the 550 isolates obtained (mean, 4.4 per patient), 143 were aerobes (representing 16 species or groups) and 407 were anaerobes (representing 40 species or groups) . Aerobes were isolated from 86% of patients-alone in 20 cases and together with anaerobes in 87 . The most common aerobic isolates were Streptococcus pyogenes (isolated from 45% of patients), Streptococcus milleri group organisms (27%), Haemophilus influenzae (11%), and viridans streptococci (11%) . Anaerobes were isolated from 82% of the samples and as a sole finding from 15 abscesses . Fusobacterium necrophorum and Prevotella melaninogenica were both isolated from 38% of patients, Prevotella intermedia from 32%, Peptostreptococcus micros from 27%, Fusobacterium nucleatum from 26%, and Actinomyces odontolyticus from 23% . The rate of previous tonsillar/peritonsillar infections was lowest (25%) among patients infected with S . pyogenes and highest (52%) among those infected with F . necrophorum (P < .01) . Recurrences and/or related tonsillectomies were more common among patients infected with F . necrophorum than among those infected with S . pyogenes (57% vs . 19%; P < .0001) or with S . milleri group organisms (43% vs . 19%; P < .05) . beta-Lactamase was produced by only 38% of the 73 isolates of Prevotella species tested; however, 56% of the 36 patients studied harbored one or more such strains.

Am J Epidemiol, 1993 Jun 1, 137(11), 1221 - 8
Cost-benefit analysis for the use of Haemophilus influenzae type b conjugate vaccine in Santiago, Chile; Levine OS et al.; Cost-benefit analyses can be integral to the evaluation of interventions in developing countries . The authors compare the potential benefits to the Chilean Ministry of Health, in terms of treatment costs averted, by prevention of Haemophilus influenzae type b (HIB) invasive disease, with the costs of adding HIB conjugate vaccine to the diphtheria-tetanus-pertussis (DTP) immunization routinely administered to infants . In their basecase model, over a 10-year period (1991-2000), vaccination against HIB will prevent 1,229 cases of HIB invasive disease, including 713 cases of meningitis, 107 of whom would suffer severe, long-term sequelae, and between 29 and 116 deaths . Assuming a cost of US$1 for a full three-dose regimen of vaccine, the benefit/cost ratio of 1.66, with a net discounted savings of over $403,225, illustrates that HIB vaccine can be cost-beneficial . Sensitivity analyses which alter each of the variables in the analysis indicate that if the true incidence of HIB disease is twice the published rate, then three doses of vaccine remains cost-beneficial at US#3PIP: Health practitioners reviewed the clinical records of all 6-60 month old children who were treated for meningitis caused by Haemophilus influenzae type b (HIB) in 1989-1990 at Roberto del Rio Children's Hospital in Santiago, Chile, to estimate costs for all phases of meningitis treatment (ambulatory visits, hospitalization, and follow-up) . They also estimated annual HIB incidence . They determined the cost of adding HIB conjugate vaccine to the DTP vaccine . They assumed a cost of US$1 for a full 3-dose regimen of vaccine . They then conducted a cost benefit analysis of the use of HIB conjugate vaccine to prevent invasive HIB disease in Santiago . The National Health Service had to pay an average of US$1301/case of HIB meningitis and US$887/case of HIB invasive disease other than meningitis, including pre- and post-hospitalization costs and adjustment for frequency of sequelae . Several factors indicated that the estimates were actually underestimates . For example, the researchers did not take into account herd immunity and the fact that sequelae often do not appear until the children are older . The addition of the HIB conjugate vaccine to the immunization program would prevent at least 1229-3111 cases of HIB invasive disease, disabling sequelae, and deaths during a 10-year period . Further, it would save the National Health Service more than US$403,225 . The benefit/cost ratio was 1.66 . The researchers changed each of the variables in the cost benefit analysis . These sensitivity analyses revealed that if the true incidence of HIB disease were 2 times greater than the based on reported data, the 3 doses of HIB conjugate vaccine would still have a cost benefit of US$3 . These results indicated that adding HIB conjugate vaccine would exert a considerable public health and cost benefit . Cost benefit analyses of vaccines would also prove useful to decision-makers in other developing countries .

J Clin Microbiol, 1993 Jun, 31(6), 1575 - 8
Detection of 2-eicosanol by gas chromatography-mass spectrometry in sputa from patients with pulmonary mycobacterial infections; Alugupalli S et al.; A total of 96 sputum specimens from patients with suspected or known mycobacterial and nonmycobacterial pulmonary infections were analyzed by gas chromatography-mass spectrometry for the presence of 2-eicosanol . This secondary alcohol was detected in all of the 25 sputum specimens culture positive for Mycobacterium tuberculosis, in 7 of the 9 sputum specimens culture positive for M . avium complex, and in all 3 of the studied sputum specimens associated with M . malmoense . The alcohol was not detected in any of the 45 culture-negative sputum specimens or in 14 sputum specimens culture positive for Staphylococcus aureus, Pseudomonas aeruginosa, Haemophilus influenzae, and Streptococcus pneumoniae . The ratio of tuberculostearic acid to 2-eicosanol was much lower in sputum samples culture positive for mycobacteria than in the corresponding in vitro-grown cultures . The present findings indicate that 2-eicosanol may be useful as a chemical marker for rapid diagnosis of pulmonary infections caused by the M . avium complex, M . malmoense, and M . tuberculosis.

Semin Respir Infect, 1993 Jun, 8(2), 104 - 15
Bacterial pneumonia in HIV-infected patients; Daley CL; Individuals infected with the human immunodeficiency virus (HIV) are more susceptible to bacterial infections because of defects in both cellular and humoral immunity . Streptococcus pneumoniae and Haemophilus influenzae are the most common causes of bacterial pneumonia in HIV-infected patients . However, more unusual bacteria can also cause pneumonia . Response to therapy is generally good for infections caused by pyogenic organisms, and complications are relatively few . Unfortunately, infections caused by Rhodococcus equi and Nocardia species are associated with significant morbidity and mortality . Moreover, the duration of therapy is long, and relapes are common . Prevention of bacterial pneumonia is an important part of the care of HIV-infected patients; the 23 valent pneumococcal vaccine is currently recommended for all HIV-infected patients . The role of other preventative measures remains unknown.

Oral Microbiol Immunol, 1993 Jun, 8(3), 134 - 40
Killing of Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus by human polymorphonuclear leukocytes in serum and saliva; Holm A et al.; The ability of polymorphonuclear leukocytes from human peripheral blood to kill Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus was examined with fresh isolates and laboratory strains from each species (5 strains within each group) under different conditions . Bacterial cells were mixed with a polymorphonuclear leukocyte suspension in the presence of either active serum or heat-inactivated serum or active serum together with sterile-filtered saliva . Surviving bacteria were determined by counting the number of bacterial colony-forming units in the mixtures after a 60-min incubation at 37 degrees C . Mixtures without polymorphonuclear leukocytes served as controls for the evaluation of the degree of killing of the bacteria . In general, A . actinomycetemcomitans resisted phagocytic killing to a greater extent than H . aphrophilus, and the killing of the former species mainly depended on the presence of heat-labile serum components, probably complement factors . Laboratory strains of A . actinomycetemcomitans were more easily killed than fresh isolates . The presence of saliva in the reaction mixtures decreased the degree of killing . However, strain-dependent variations in the killing were found under either condition . The leukotoxic activity of A . actinomycetemcomitans strains, determined by a {51Cr}-release assay, was not correlated with the resistance of these strains to the phagocytic killing . The results point out a strain-dependent difference in the ability of A . actinomycetemcomitans to evade the inflammatory response associated with polymorphonuclear leukocytes . This difference may constitute a potential virulence factor for this periodontopathogen . Furthermore, the leukotoxicity of the strains is not the main determinant that modifies the interaction of A . actinomycetemcomitans with human neutrophils.

Oral Microbiol Immunol, 1993 Jun, 8(3), 129 - 33
Multivariate chemosystematics demonstrate two groups of Actinobacillus actinomycetemcomitans strains; Brondz I et al.; Chemical analysis by us has indicated that Actinobacillus actinomycetemcomitans is not a homogeneous species . The present study used chemometric methods and a multitude of chemical characters to examine this further . Strains were characterized by cell sugar and fatty acid contents, lysis kinetics during EDTA and EDTA plus lysozyme exposure, methylene blue reduction, and API ZYM enzymatic assessment of whole cells and outer membrane vesicles/fragments . In total, 41 quantitative variables were analyzed from each of 9 strains and treated with principal component analysis and soft independent modeling of class analogy . These methods divided A . actinomycetemcomitans into 2 strain groups . One group contained ATCC 33384, ATCC 29522, FDC 2112 and FDC 2043; the other comprised ATCC 29524, ATCC 29523, FDC 2097, FDC 511 and FDC Y4 . With an F-test, the groups (classes) of A . actinomycetemcomitans strains could be distinguished at 95% confidence limits . Both groups were distinct from members of the genera Haemophilus and Pasteurella (Haemophilus aphrophilus, Haemophilus paraphrophilus, Haemophilus influenzae, Pasteurella multocida and Pasteurella haemolytica).

Zhonghua Liu Xing Bing Xue Za Zhi, 1993 Jun, 14(3), 136 - 8
{A study on the carrier state of Haemophilus influenzae in pharynx in healthy children in Beijing Area}; Liu Y; One hundred and fifteen healthy children in 2 kindergartens of Beijing City were enrolled in a study for carrier state of Haemophilus influenzae (HI) in pharynx . Nontypable HI flora was found in 32.2% (37/115) in this group . There were no significant differences of carrier state in sex, age, and season in these children . Antibiotic sensitivity test showed that some HI strains isolated were resistant to ampicillin and tetracycline (5/34 vs 4/34), most strains resistant to SMZ Co (21/34).

Zentralbl Bakteriol, 1993 Jun, 279(1), 60 - 74
Characterization of bovine Haemophilus somnus by biotyping, plasmid profiling, REA-patterns and ribotyping; Fussing V et al.; A total of 105 strains of H . somnus isolated from cattle in Denmark and other countries during 1982-1991 were compared with regard to biotypes (fermentation of 8 different sugars), plasmid profiles, Taq1 restriction endonuclease analysis of chromosomal DNA (REA-typing) and EcoRI-generated DNA restriction fragment length polymorphisms of rRNA genes (ribotyping) . Eighty-four strains originating from cases of pneumonia, and 21 originating from the genitals of bulls were included in this study . Biotyping yielded 21 different types . Twenty-two of the isolates contained plasmids, and these were divided into 12 distinct plasmid profiles . Analysis of chromosomal DNA restriction patterns, resulted in 33 different REA patterns and 16 different ribopatterns in the investigated strains . Biotypes, REA-types, and ribotypes generally showed good correlation, whereas plasmid profiles did not correlate with any other typing method . Seventy-eight percent of all Danish isolates from pneumonia belonged to the same REA-, and ribotype, indicating a single clone . Furthermore, a single strain from semen belonged to this type, but generally strains isolated from the genital tract showed little homology to strains isolated from cases of pneumonia with regard to REA-, and ribotypes . The typing methods applied in the present investigation appeared to be useful indicators of epidemiological relatedness between H . somnus strains from cattle, and might be used for epidemiological investigations as well as for taxonomic studies of this species.

Zentralbl Bakteriol, 1993 Jun, 279(1), 51 - 9
Genetic relationship of strains of Haemophilus aphrophilus, H . paraphrophilus, and Actinobacillus actinomycetemcomitans studied by ribotyping; Sedlacek I et al.; Strains of H . aphrophilus, H . paraphrophilus, and A . actinomycetemcomitans are phenotypically very similar . Ribotyping of 24 strains of H . aphrophilus, 22 strains of H . paraphrophilus, 8 strains of A . actinomycetemcomitans, and one strain each of the species Pasteurella aerogenes, H . parahaemolyticus, and the genus Capnocytophaga was studied using a non-radioactive digoxigenin labelled probe based on E . coli 16S- and 23S-ribosomal RNA . Restriction fragments were generated using restriction enzyme EcoRI . The ribotypes were analysed by a numerical approach using UPGMA clustering . Two major clusters were seen: One contained all A . actinomycetemcomitans strains, the other all H . aprophilus and all except one H . paraphrophilus strain intermingled between each other . The H . paraphrophilus strain not found in the H . aphrophilus/H . paraphrophilus cluster, the H . parahaemolyticus, P . aerogenes, and the Capnocytophaga strains clustered separately from each other and the two major clusters . The H . paraphrophilus strain with the deviating ribotype was atypical in other respects: it neither did ferment lactose nor mannose and it was isolated from a deer in contradiction to the remaining H . paraphrophilus strains, which were human isolates . This study supports the view that H . aphrophilus and H . paraphrophilus should be regarded as one species separated from A . actinomycetemcomitans.

Zentralbl Bakteriol, 1993 Jun, 279(1), 35 - 44
Phylogeny of the Pasteurellaceae as determined by comparison of 16S ribosomal ribonucleic acid sequences; Dewhirst FE et al.; Previously, virtually complete 16S ribosomal ribonucleic acid sequences were determined for 54 strains of species in the family Pasteurellaceae . The sequences for 16 additional strains have been determined, bringing the total number of strains sequenced to 70 . The additional strains include: Actinobacillus hominis, A . muris, A . salpingitis, Pasteurella bettyae, P . mairii, P . testudinis, and Bisgaard taxa 2, 3, 5, 6, 7, 8, 9, 13, and 14 (2 strains) . A phylogenetic tree was constructed based upon sequence similarity using the Neighbor-Joining method . The additional sequence information and phylogenetic analysis generally supported our previously described phylogenetic structure for the family Pasteurellaceae . Cluster 1, containing Haemophilus sensu stricto, was unchanged . P . mairii was closely related to P . aerogenes and Bisgaard taxon 6 was related to H . somnus in Cluster 2 . A . salpingitidis and Bisgaard taxa 2, 3, 7, and 13 fell in Cluster 3 which contains Pasteurella sensu stricto . A . hominis was closely related to Actinobacillus sensu stricto species in Cluster 4A . Bisgaard taxa 5, 8, 9 and P . bettyae fell in Cluster 4B . A . muris was related to P . pneumotropica in Cluster 5 . Haemophilus parainfluenzae strains branched deeply as a 6th cluster . Bisgaard taxon 14 and P . testudinis formed a 7th cluster which branched deeper than any previously described clusters in the family Pasteurellaceae . The branching was extremely complex and taxonomic division of the family into phylogenetically and phenotypically coherent genera will be difficult.

Presse Med, 1993 May 29, 22(19), 899 - 902
{Infectious sinusitis in HIV infection . Clinical and therapeutic data on 20 patients}; Lacassin F et al.; To assess the clinical presentation and outcome of infectious sinusitis in HIV-infected patients, we analyzed in a retrospective study, the records of HIV-infected patients hospitalized from June 1986 to November 1989 . Twenty-eight episodes of infectious sinusitis, defined by radiological signs, were recorded in 20 HIV-infected patients . Clinical presentation suggestive of acute sinusitis was inconstant and in 6 episodes a persistent fever was the only symptom . Concomitant pneumonia was detected in 8 episodes . Bacteria were isolated in 8 episodes, and in 4 of them, Haemophilus influenzae was identified . Clinical relapses occurred in 8/20 patients, requiring a surgical drainage in 3 cases . The frequency of relapses and the possibility of chronicity justify a more prolonged and aggressive therapy in infectious sinusitis occurring in HIV-infected patients.

Am Fam Physician, 1993 May 15, 47(7), 1595 - 603
Practical approach to bacterial meningitis in childhood; Pohl CA; The classic triad of headache, fever and nuchal rigidity that occurs in adults with bacterial meningitis is often absent in children . Evaluation of the cerebrospinal fluid remains the gold standard for the diagnosis of bacterial meningitis . The choice of antibiotic therapy is dependent on the most likely age-specific pathogen and the drug's bactericidal activity in cerebrospinal fluid . Routine fluid restriction is no longer recommended in the initial management of critically ill patients . Dexamethasone has become an important adjunct to antimicrobial therapy for meningitis due to Haemophilus influenzae type b . Prevention, especially administration of H . influenzae type b vaccine at an early age, is probably the most effective way to reduce the significant mortality and morbidity associated with bacterial meningitis in children.

Postgrad Med, 1993 May 15, 93(7), 43 - 6, 49-52
Bacterial pneumonia . S pneumoniae and H influenzae are the villains; Wisinger D; Bacterial pneumonia isn't what it used to be . The most common causes, Streptococcus pneumoniae and Haemophilus influenzae, are developing strains that are resistant to powerful antibiotics: How do you choose a therapeutic agent? New organisms are being discovered to be culprits in this disease: How do you keep track of them? New drugs are being developed every day: How does that help if initial treatment is almost always empirical? Dr Wisinger identifies the problems and offers advice.

Am J Ophthalmol, 1993 May 15, 115(5), 623 - 8
The penetration of oral ciprofloxacin into the aqueous humor, vitreous, and subretinal fluid of humans; Lesk MR et al.; We examined ciprofloxacin levels in the aqueous humor, vitreous, or subretinal fluid in 40 patients undergoing cataract extraction, vitrectomy, or scleral buckling . Ciprofloxacin, 750 mg, was administered orally an average of 17 1/2 and 5 1/2 hours preoperatively . We obtained mean ciprofloxacin levels of 0.53 microgram/ml in aqueous humor, 0.51 microgram/ml in vitreous, and 0.71 microgram/ml in subretinal fluid . These vitreous levels exceed the minimum inhibitory concentration (MIC)90 of Staphylococcus epidermidis, Propionibacterium species, Pseudomonas aeruginosa, Proteus mirabilis, and Haemophilus influenzae, as well as the MIC70 of S . aureus and Bacillus cereus . Therefore, ciprofloxacin may have a role in the management and prevention of endophthalmitis.

Presse Med, 1993 May 15, 22(17), 815 - 6
{Haemophilus parainfluenzae meningitis in an 8-year-old boy}; Poupart MC et al.; Invasive infections caused by Haemophilus parainfluenzae, a saprophyte of the respiratory tract, are exceptional and should arise suspicion of abnormalities in immunocompetence . So far, about thirty cases of H . parainfluenzae meningitis affecting neonates, infants or adults have been published . A case of such meningitis in an 8-year old boy without any risk factor is reported here.

J Clin Microbiol, 1993 May, 31(5), 1362 - 3
Evaluation of the RapID NH system for identification of Haemophilus somnus, Pasteurella multocida, Pasteurella haemolytica, and Actinobacillus pleuropneumoniae isolated from cattle and pigs with respiratory disease; Salmon SA et al.; Haemophilus somnus, Pasteurella haemolytica, Pasteurella multocida, and Actinobacillus pleuropneumoniae from cattle and pigs with respiratory disease were used to evaluate the RapID NH system (Innovative Diagnostics, Atlanta, Ga.) . Minor modifications of the RapID NH system to include animal source and growth requirements would permit the identification of all isolates tested.

J Clin Microbiol, 1993 May, 31(5), 1246 - 50
Testing of Streptococcus pneumoniae for resistance to penicillin; Marshall KJ et al.; The increasing prevalence of penicillin-resistant Streptococcus pneumoniae requires antibiotic susceptibility tests that can be done with greater ease and reliability . We measured the MIC of penicillin for pneumococci by the tube macrodilution method with Mueller-Hinton broth (MHB), Haemophilus Test Medium (HTM), Todd-Hewitt broth with 0.5% yeast extract (THY), and MHB with 3% lysed horse blood (LHB) . Eight (19%) and 6 (14%) of 42 pneumococcal isolates failed to generate turbid growth in MHB and HTM, respectively, whereas all pneumococcal isolates did so in THY and LHB . For those strains that replicated to turbidity, the mean MICs of penicillin were lower in MHB and HTM than in THY and LHB, with differences being significant (P < 0.05) for comparisons with LHB . Four isolates appeared to be penicillin susceptible in HTM but were actually moderately resistant in THY and LHB, and two isolates appeared to be moderately resistant but were resistant . A similar failure to detect resistance was seen with MHB . S . pneumoniae ATCC 49619, a moderately penicillin-resistant strain that has been proposed for quality control testing, gave variable results in MHB or THM and appeared to be susceptible to penicillin in some assays, whereas the MICs for S . pneumoniae ATCC 49619 in THY or LHB fell within a twofold dilution range, with geometric means of 0.16 and 0.18 micrograms/ml, respectively . Pneumococcal isolates thus may appear falsely susceptible to penicillin when tested in MHB or HTM . LHB remains the standard medium; however, because THY is an easily prepared clear medium that can be used in automated systems and appears to yield results similar to those obtained with LHB, THY deserves consideration for routine use.

J Med Microbiol, 1993 May, 38(5), 378 - 83
Outer-membrane protein and immunoblot analysis of Australian isolates of Haemophilus influenzae; Hansman D et al.; Strains of Haemophilus influenzae isolated from children in South Australia and the Northern Territory with systemic infections (mostly meningitis or epiglottitis) were subjected to serotyping, biotyping, outer-membrane protein (OMP) analysis and immunoblot subtyping . All 65 isolates examined were from blood or cerebrospinal fluid; 59 (91%) of the strains were identified as type b and the remainder as either type a (two strains) or non-typable (four strains) . Of the 59 type b strains, 45 (76%) belonged to a single OMP subtype (equivalent to subtype 3L in the Barenkamp scheme); the remaining type b strains belonged to five other OMP subtypes . No correlation was apparent between OMP subtype and geographical region, clinical diagnosis or antimicrobial drug susceptibility pattern . Immunoblot subtyping enabled nine (18%) of 41 strains belonging to the principal OMP subtype to be distinguished from the remainder.

J Infect Dis, 1993 May, 167(5), 1210 - 2
Immunogenicity of Haemophilus influenzae type b conjugate vaccine in children with congenital asplenia; Webber SA et al.; The immunogenicity of Haemophilus influenzae type b polysaccharide-protein conjugate vaccines in congenitally asplenic children is unknown . The short-term immunogenicity of the H . influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine was therefore assessed in 10 children with congenital asplenia by measuring antipolyribosyl-ribitol phosphate antibody titers . An excellent antibody response was seen in 9 children (mean geometric titer in responders after immunization 44.7 micrograms/mL; range, 2.59-402) . The remaining child responded to a booster dose . Further studies are required to assess whether H . influenzae type b conjugate vaccines are immunogenic in infancy in the presence of congenital asplenia.

J Infect Dis, 1993 May, 167(5), 1206 - 10
Humoral immune response of humans to lipooligosaccharide and outer membrane proteins of Haemophilus ducreyi; Alfa MJ et al.; The humoral immune response to purified lipooligosaccharide (LOS) and outer membrane proteins (OMP) of Haemophilus ducreyi was evaluated . Sera from chancroid-endemic (Uganda, Kenya) and -nonendemic (Canada) countries were tested by an ELISA . The response to OMPs was cross-reactive with other Haemophilus species, and elevated levels of antibody were detected in patients that did not have chancroid . The LOS component stimulated an H . ducreyi-specific immune response that was detected only in patients with chancroid . The sensitivity of the LOS ELISA was 96% (95% confidence interval, 89.9%-100%) and the specificity was 97% (95% confidence interval, 95.8%-98.2%) . Thus, the anti-H . ducreyi LOS immune response is a significant diagnostic and epidemiologic indicator.

Chest, 1993 May, 103(5), 1502 - 7
Aerobic and anaerobic microbiology of empyema . A retrospective review in two military hospitals; Brook I et al.; The microbiology and clinical features of empyema were studied retrospectively in 197 patients whose specimens yielded bacterial growth after inoculation for aerobic and anaerobic bacteria . Three hundred forty-three organisms (216 aerobic or facultative and 127 anaerobic organisms) were isolated . Aerobic bacteria were isolated in 127 (64 percent) patients, anaerobic bacteria in 25 (13 percent), and mixed aerobic and anaerobic bacteria in 45 (23 percent) . The predominant aerobic or facultative organisms were Streptococcus pneumoniae (70 isolates), Staphylococcus aureus (58), Escherichia coli (17), Klebsiella pneumoniae (16), and Haemophilus influenzae (12) . The predominant anaerobes were pigmented Prevotella and Porphyromonas species (24), Bacteroides fragilis group (22), anaerobic cocci (36), and Fusobacterium species (20) . beta-Lactamase-producing organisms were recovered in 49 (38 percent) of 128 tested specimens . These included all 42 tested S aureus and 15 B fragilis group, 4 of 9 K pneumoniae, 3 of 9 H influenzae, 3 of 8 pigmented Prevotella and Porphyromonas species, and 2 of 6 E coli . Most patients from whom S pneumoniae and H influenzae were recovered had pneumonia, and most patients with S aureus had pneumonia, aspiration pneumonia, and lung abscesses . The recovery of anaerobic bacteria was mostly associated with the concomitant diagnosis of aspiration pneumonia, and lung, subdiaphragmatic, dental, and oropharyngeal abscesses . These data highlight the importance of anaerobic bacteria in selected cases of empyema.

Infect Immun, 1993 May, 61(5), 2257 - 9
Antigenic analysis of the major outer membrane protein of Haemophilus somnus with monoclonal antibodies; Tagawa Y et al.; The major outer membrane protein of Haemophilus somnus possesses at least five distinct epitopes . Three surface-exposed epitopes on the major outer membrane protein include a conserved epitope with potential for development of a vaccine and a diagnostic test and two variable epitopes responsible for antigenic differences among strains; the remaining two epitopes are well preserved among strains but not exposed on the cell surface.

Infect Immun, 1993 May, 61(5), 2233 - 7
Isolation, expression, and nucleotide sequencing of the pilin structural gene of the Brazilian purpuric fever clone of Haemophilus influenzae biogroup aegyptius; St Geme JW 3rd et al.; In this study we isolated the pilin gene from the Brazilian purpuric fever (BPF) clone of Haemophilus influenzae biogroup aegyptius, expressed the gene in Escherichia coli, and determined its nucleotide sequence . Comparison of the nucleotide sequence of the BPF pilin gene with the sequences of pilin genes from strains of H . influenzae sensu stricto demonstrated a high degree of identity . Consistent with this observation, hemagglutination inhibition studies performed with a series of glycoconjugates indicated that BPF pili and H . influenzae type b pili possess the same erythrocyte receptor specificity.

Infect Immun, 1993 May, 61(5), 1950 - 7
Evaluation of mixtures of purified Haemophilus influenzae outer membrane proteins in protection against challenge with nontypeable H . influenzae in the chinchilla otitis media model; Green BA et al.; Nontypeable Haemophilus influenzae (NTHi) is one of the leading causative agents of bacterial otitis media, and no vaccine has been shown to be effective against it . Three outer membrane lipoproteins of NTHi have been investigated extensively and are leading candidates for inclusion in a vaccine against this organism . Hi-PAL (P6), recombinant PCP (rPCP), and e (P4) proteins are antigenically conserved among NTHi strains and elicit bactericidal and protective antibodies . A genetic fusion of the rPCP and Hi-PAL proteins has also been reported . Mixtures of these proteins were used for active immunization experiments in the chinchilla model of otitis media . Chinchillas were immunized either with a mixture of all three lipoproteins or with the mixture of rPCP-PAL hybrid plus e protein . When these animals were challenged with a NTHi strain injected directly into the middle ears, no protection from infection or disease, as measured by otoscopy, was observed in either group . However, effusion and inflammation measured by tympanometry were significantly reduced in animals immunized with the three lipoproteins . Animals that had been immunized with either whole NTHi cells or total outer membranes and then challenged with the homologous strain were significantly protected from both infection and disease, as determined by tympanometry and otoscopy . Unlike other animals antisera, chinchilla antisera against the purified proteins had no bactericidal activity against NTHi but did fix complement on the cell surface . Thus, the chinchilla immune responses to mixtures of these lipoproteins differ from the immune responses observed in other animal species . Further evaluation of these proteins for their vaccine potential remains to be done.

Infect Immun, 1993 May, 61(5), 1793 - 8
Molecular cloning, nucleotide sequence, and characterization of lppB, encoding an antigenic 40-kilodalton lipoprotein of Haemophilus somnus; Theisen M et al.; Haemophilus somnus is a facultative intracellular pathogen which causes a wide range of diseases in cattle . To identify putative virulence determinants, a genomic library of H . somnus in Escherichia coli was screened for Congo red binding, a property associated with virulence in pathogenic bacteria, and subsequently with bovine hyperimmune sera raised against H . somnus HS25 . A Congo red-binding clone carrying a 1.8-kb DNA insert was found to encode a strongly seroreactive LppB protein with an apparent molecular weight of 40,000 . The nucleotide sequence of the entire DNA insert was determined . Two open reading frames coding for polypeptides with calculated molecular weights of 21,893 and 30,721 were identified . The larger open reading frame encoded LppB, while the smaller reading frame encoded a nonseroreactive protein with a relative molecular mass of approximately 18 kDa . The 16 amino-terminal amino acids of the deduced LppB polypeptide showed strong sequence homology to the signal peptide of secreted bacterial proteins, and the sequence Leu-Ala-Ala-Cys at the putative cleavage site corresponds to the consensus cleavage sequence of bacterial lipoproteins . Synthesis of the mature LppB lipoprotein in H . somnus was inhibited by globomycin, a specific inhibitor of signal peptidase II . LppB was localized to the outer membrane of H . somnus.

Infect Immun, 1993 May, 61(5), 1750 - 5
Characterization of a heat-modifiable outer membrane protein of Haemophilus somnus; Tagawa Y et al.; In immunoblot analysis, a murine monoclonal antibody (MAb), 27-1, which was produced to an outer membrane protein (OMP) of Haemophilus somnus, showed that a major OMP is heat modifiable, having a molecular mass of 28 kDa when the N-lauroylsarcosine-insoluble OMP preparation was solubilized at 60 degrees C and a mass of 37 kDa when the OMP preparation was solubilized at 100 degrees C . The heat-modifiable OMP reacted intensely with convalescent sera obtained from calves with experimental H . somnus pneumonia in immunoblot analysis . Immunoelectron microscopic and antibody absorption studies revealed that the MAb 27-1 epitope was not surface exposed on the intact bacterium . However, a decrease in antibody reactivity to the heat-modifiable OMP in immunoblot analysis after absorption of convalescent serum with intact bacterial cells of H . somnus suggests that a surface-exposed portion of the heat-modifiable OMP is expressed on the intact bacterium . MAb 27-1 reacted with 45 of 45 strains of H . somnus tested in immunoblot analysis . The apparent molecular mass of the antigen varied among strains, and five reactivity patterns demonstrated by MAb 27-1 were observed . MAb 27-1 also reacted with six species in the family Pasteurellaceae, Escherichia coli, and Salmonella dublin, but not with the other eight species of gram-negative bacteria . The heat-modifiable OMP of H . somnus showed immunological cross-reactivity with the OmpA protein of E . coli K-12 and significant N-terminal amino acid sequence homology with the OmpA proteins of gram-negative bacteria . We conclude that a major, 37-kDa heat-modifiable OMP of H . somnus, which elicits an antibody response in H . somnus-infected animals, is a common antigen among H . somnus strains tested and is structurally related to the OmpA protein of E . coli.

Infect Immun, 1993 May, 61(5), 1735 - 42
Haemophilus ducreyi adheres to but does not invade cultured human foreskin cells; Alfa MJ et al.; Haemophilus ducreyi is the etiologic agent of the localized genital ulcer disease known as chancroid . The pathogenesis of this organism is poorly understood . The role of attachment in the disease process has not been evaluated . In this study, 125I-H . ducreyi was used to quantitatively evaluate the interaction of virulent and avirulent H . ducreyi strains with human foreskin cells . Using this in vitro model system, we demonstrated that, at 22 and 35 degrees C, the attachment of virulent H . ducreyi 35000 to human foreskin cells was significantly more marked than that of avirulent H . ducreyi A77 . Although H . ducreyi penetrated between human foreskin cells, internalization was not a major component . Our competition assay data suggest that the attachment mechanism of H . ducreyi may be similar to that of Neisseria gonorrhoeae . We speculate that the attachment and microcolony formation of virulent H . ducreyi may provide a mechanism for bacterial localization and evasion of host defenses.

Antimicrob Agents Chemother, 1993 May, 37(5), 1015 - 24
Preincubation of Haemophilus influenzae with subinhibitory concentrations of macrolides: influence on human neutrophil chemiluminescence; Bonnet M et al.; Preincubation of Haemophilus influenzae with antibiotics may influence opsonophagocytosis as studied by chemiluminescence . Two strains of H . influenzae (strain 1 {type b} and strain 2 {uncapsulated}) were pretreated with erythromycin, roxithromycin, clarithromycin, and azithromycin for 1 h in Haemophilus test medium (the last 25 min was either without serum or with 10% fresh serum or 10% decomplemented serum) . Human neutrophils were stimulated with a pretreated or control inoculum at four different bacterium/neutrophil ratios and tested for luminol chemiluminescence with an LKB luminometer . The results were normalized for bacterium/neutrophil ratio and compared by the two-sided Wilcoxon test . Pretreatment of bacteria with one-half of the MICs of erythromycin, clarithromycin, and roxithromycin produced nonsignificant (P > 0.05) increases in the chemiluminescence response (means of 23% for strain 1 and 4% for strain 2) . Pretreatment with azithromycin at one-half of the MIC produced an increase in the chemiluminescence response induced by serum-opsonized strain 1 (320% +/- 36% {mean +/- standard error of the mean}) and strain 2 (107% +/- 20%) (P < 0.05) . This increase was concentration dependent: for strain 1, 60% +/- 18% at one-fourth of the MIC to 440% +/- 41% at the MIC; for strain 2, 10% +/- 5% at one-fourth of the MIC to 300% +/- 20% at the MIC . For strain 1, the maximal increase with azithromycin pretreatment (at the MIC) required opsonization with fresh serum . Opsonization with decomplemented serum was associated with a 53% +/- 21% increase; this increase was 28% +/- 3% in the absence of serum . For strain 2, azithromycin reduced the lag phase of the chemiluminescence response induced by the absence of serum but did not alter the chemiluminescence response in the presence of decomplemented serum . A significant contribution of soluble factors in the enhanced response observed with bacteria preincubated with azithromycin was excluded . The increase of the chemiluminescence response with azithromycin pretreatment was probably due to improvement in complement-dependent opsonization for strain 1 and to improvement in both serum-independent and serum-dependent opsonization for strain 2.

J Bacteriol, 1993 May, 175(9), 2702 - 12
Investigation of the structural heterogeneity of lipooligosaccharides from pathogenic Haemophilus and Neisseria species and of R-type lipopolysaccharides from Salmonella typhimurium by electrospray mass spectrometry; Gibson BW et al.; Heterogeneity in the lipooligosaccharides (LOS) of pathogenic Haemophilus and Neisseria species is evident from the multiplicity of components observed with electrophoretic analyses . Knowledge of the precise structures that make up these diverse LOS molecules is clearly the key to reaching an understanding of pathogenic processes such as phase variation and molecular mimicry . Except for a few cases, little is known about the specific structural features of LOS that underlie phase variation and molecular mimicry, partly because of the inherent difficulties in the structural elucidation of these complex glycolipids . In the lipopolysaccharides (LPS) from Salmonella typhimurium and Escherichia coli, rough, or R-type, mutants have been isolated that have provided insight into the biosynthetic pathways and associated genetics that control LPS expression . Nonetheless, recent work has shown that these R-type LPS are more complex than originally thought, and significant heterogeneity is still observed, primarily in their phosphorylation states . In order to investigate the structures of LPS and LOS in a more rapid fashion, we have determined the precise molecular weights of LOS (and LPS) preparations from various Haemophilus, Neisseria, and Salmonella species by electrospray ionization-mass spectrometry . The LOS (or LPS) were first O-deacylated under mild hydrazine conditions to remove O-linked esters primarily from the lipid A portion . Under negative-ion conditions, the O-deacylated LOS yield abundant multiply deprotonated molecular ions, (M-nH)n-, where n refers to the number of protons removed and therefore determines the absolute charge state, n = z . Mass spectra from different LOS and LPS preparations have provided detailed information concerning the structural basis for LOS (and LPS) heterogeneity and corresponding saccharide compositions . The identification of sialic acid in the LOS of Haemophilus and Neisseria species and the variable phosphorylation of the core of S . typhimurium LPS have afforded insights into the biosynthetic pathways used by these organisms . Information of this type is important for understanding the underlying genetic and environmental factors controlling LOS and LPS expression.

Microb Pathog, 1993 May, 14(5), 389 - 98
The interaction of primate transferrins with receptors on bacteria pathogenic to humans; Gray-Owen SD et al.; The binding of primate transferrins by receptors in the human pathogens Neisseria meningitidis, Moraxella (Branhamella) catarrhalis, and Haemophilus influenzae was assessed and compared with the binding of anti-human transferrin monoclonal antibodies by primate transferrins . In competitive binding assays the three pathogens showed identical specificity for primate transferrins . Only human, gorilla, chimpanzee and orangutan sera were capable of blocking binding of labelled human transferrin . Direct binding assays and affinity isolation of receptor proteins confirmed that chimpanzee transferrin, but not rhesus monkey transferrin, was capable of effectively binding to the bacterial receptors . Five distinct patterns of binding were seen when five anti-human transferrin monoclonal antibodies were reacted with the primate transferrins and these patterns reflected phylogenetic relatedness of these species to humans . A monoclonal antibody which showed transferrin-binding specificity identical to that seen with the bacterial receptors was found to block binding of human transferrin by receptors in the three bacterial species.

Vet Microbiol, 1993 May, 35(1-2), 91 - 100
Differences in protein expression of Haemophilus somnus grown under conditions of iron-restriction; Wedderkopp A et al.; Outer membrane protein profiles were compared in 14 H . somnus strains isolated from brain and lung lesions as well as from the genital tract of asymptomatic carriers during in vitro growth under iron-restricted conditions . Ethylenediamine-di-O-hydroxyphenyl acetic acid (EDDA) was used to obtain iron-restricted conditions in media used for this study . The outer membrane protein profiles were studied by the discontinuous sodium dodecyl sulfate-polyacrylamide gel electrophoretic system (SDS-PAGE), and the proteins were stained with silver or transferred to nitrocellulose sheets and western blots conducted . Growth under iron-restricted conditions resulted in the induction of outer membrane proteins in most H . somnus strains examined . Studies also indicated differences among H . somnus strains in the number of induced proteins and their molecular weights but the results did not indicate a specific relationship between these strain-dependent differences and tissue trophism . Western blot analysis revealed a high degree of immunological relatedness among strains of H . somnus in their iron-regulated proteins . However, hyperimmune serum used in these assays failed to recognize certain iron-regulated proteins expressed by some H . somnus strains, a finding which may have important implications for the induction of protective immunity in cattle against this bovine pathogen.

Eur J Clin Microbiol Infect Dis, 1993 May, 12(5), 319 - 24
Evaluation of amoxicillin clavulanate twice daily versus thrice daily in the treatment of otitis media in children . Danish-Swedish Study Group; Jacobsson S et al.; A total of 311 children who had recurrent otitis media or who had experienced failure of initial treatment of acute otitis media with phenoxymethylpenicillin, amoxicillin, ampicillin esters or cefaclor were entered into a single-blind study in two parallel groups in order to compare the clinical efficacy and safety of amoxicillin/clavulanate suspension given b.i.d . or t.i.d . for seven days . The patients were examined prior to the start of treatment, at an early follow-up visit 9 to 12 days after the start of treatment and at a late follow-up visit about three weeks later . Specimens for bacteriological culture were taken from the nasopharynx at entry, at the early follow-up visit, and at the late follow-up visit if there were symptoms of otitis . Both treatment groups showed a similar response, 90% or more of the patients being cured or showing improvement at the time of the early follow-up visit . The initial nasopharyngeal cultures showed growth of Haemophilus influenzae in 53% of the patients, Moraxella catarrhalis in 43% and Streptococcus pneumoniae in 39% . After treatment, cultures showed elimination of the initial pathogens in 30% of patients in both groups and recolonization in 23% in both groups . Haemophilus influenzae was the bacteria most frequently found in the nasopharynx at the first follow-up visit . Adverse effects, which consisted mostly of gastrointestinal and dermatological reactions, tended to be more common in the b.i.d . group but the difference was not statistically significant.

Pediatr Infect Dis J, 1993 May, 12(5), 389 - 94
Outcomes of bacterial meningitis in children: a meta-analysis; Baraff LJ et al.; We abstracted the results of all English language reports of the outcomes of bacterial meningitis published after 1955 . We used hierarchical Bayesian meta-analysis to determine the overall and organism-specific frequencies of death and persistent neurologic sequelae in children 2 months to 19 years of age . A total of 4920 children with acute bacterial meningitis were included in 45 reports that met the inclusion criteria . Children described in the 19 reports of prospectively enrolled cohorts from developed countries had lower mortality (4.8% vs . 8.1%) and were more likely to have no sequelae (82.5% vs . 73.9%) . In these 19 studies 1602 children were evaluated for at least 1 sequela after hospital discharge . The mean probabilities of these sequelae were: deafness, 10.5%; bilateral severe or profound deafness, 5.1%; mental retardation, 4.2%; spasticity and/or paresis, 3.5%; seizure disorder, 4.2%; and no detectable sequelae, 83.6% . Mean probabilities of outcomes varied significantly by etiologic bacteria, e.g . mortality: Haemophilus influenzae, 3.8%; Neisseria meningitis, 7.5%; Streptococcus pneumoniae, 15.3%.

Pediatr Infect Dis J, 1993 May, 12(5), 362 - 7
Comparison of the epidemiology and cost of Haemophilus influenzae type b disease in five western countries; Clements DA et al.; To determine and compare the cost of Haemophilus influenzae type b (Hib) disease in Australia, Finland, Israel, Switzerland and the United Kingdom a collaborative study was undertaken . The incidence of Hib disease varies in these 5 countries from 34 to 58.5 cases per 100,000 children less than 5 years of age . Although the incidence of meningitis in this age group is similar (between 18 and 26/100,000) in these countries, the incidence of epiglottitis varies from 0 to 22.7/100,000 . The cost of hospitalization and the frequency of sequelae are similar for 4 of the 5 countries; however, the break even cost of a vaccination program to prevent 90% of Hib disease is estimated to vary from $22 to $84 per child (US$) . Because of a lower incidence of Hib disease and lower cost for hospitalization, these costs are considerably less than those for the United States ($301.64 using similar calculations).

Int J STD AIDS, 1993 May-Jun, 4(3), 171 - 3
The suppressive effect of serum samples from patients with chancroid on human mononuclear cells correlates with the clinical picture and is interleukin-2-dependent; Korting HC et al.; Plasma samples from patients with chancroid diagnosed both on clinical and microbiological grounds were assessed for their ability to inhibit mitogen-induced proliferation of human lymphocytes from healthy donors . All serum samples analysed suppressed phytohaemagglutinin A (PHA) blastogenic response . A significant difference in the observed extent was seen when serum samples from patients with and without associated lymphadenopathy were compared (P < 0.05) . Using an interleukin-2 (IL-2)-dependent cell line it could be demonstrated that the addition of patients' plasma to cultured cells markedly depressed mitogen-induced IL-2 synthesis . Results presented suggest that cell-mediated mechanisms play a role in the pathogenesis of infection due to Haemophilus ducreyi.

Enferm Infecc Microbiol Clin, 1993 May, 11(5), 260 - 2
{Roxithromycin in the treatment of community-acquired pneumonia}; Antela A et al.; BACKGROUND: The aim of the present study was to prospectively evaluate the efficacy and tolerance of roxithromycin in the empiric treatment of extra-hospitalary pneumonias in immunocompetent adult patients . METHODS: Over a 12 month period 101 patients with extra-hospitalary pneumonia who attended the Emergency Department were studied . Of these, 53 were treated as out patients (5 with amoxicillin-clavulanic, 25 with erythromycin and 23 with roxithromycin at daily doses of 300 mg for 10 days) . The treatment was randomly chosen, with no patient selection, thus making heterogeneous groups and, therefore, the study could not be comparative . RESULTS: In patients receiving roxithromycin, an etiologic diagnosis was achieved in 15 cases (65.3%), with Mycoplasma pneumoniae, being the most frequent pathogen (10 cases), followed by Streptococcus pneumoniae (3), Chlamydia pneumoniae (1) and Haemophilus influenzae (1) . The mean duration of fever was 1.9 days, 6.7 days for respiratory manifestations and resolution of the radiographic infiltrate 11.6 days . The evolution was good in all the patients with no secondary effects or relapse occurring in any patient . CONCLUSION: Roxithromycin is an effective, safe and comfortable antibiotic in the treatment of infections of the lower respiratory tract acquired in the community.

Ann Clin Lab Sci, 1993 May-Jun, 23(3), 203 - 6
Haemophilus parainfluenzae endocarditis in a patient with mitral valve prolapse; Greene JN et al.; Haemophilus parainfluenzae is a frequent cause of "culture-negative" endocarditis (i.e., endocarditis owing to a fastidious organism which may require longer incubation periods and/or enrichment media for detection compared to traditional pathogens) . More cases will probably be identified with improvements in growth and isolation techniques . A case of H . parainfluenzae endocarditis is presented in a patient with mitral valve prolapse, which illustrates the difficulty in diagnosing endocarditis when initial blood cultures are negative . Particularly, it emphasizes the difficulty in selecting appropriate antibiotic therapy since beta-lactamase producing organisms are being isolated with increased frequency . This report is unique in that it documents successful treatment with a cephalosporin and what is, to our knowledge, the third reported case of a beta-lactamase producing H . parainfluenzae causing endocarditis . The authors believe that beta-lactamase stable second or third generation cephalosporins should constitute initial treatment of H . parainfluenzae endocarditis until sensitivity studies become available, since beta-lactamase production by this organism would nullify the effect of the previous agent of choice, ampicillin.

Pharmacotherapy, 1993 May-Jun, 13(3), 189 - 201
The role of fluoroquinolones in sexually transmitted diseases; Tartaglione TA et al.; The management of sexually transmitted diseases (STDs) has reached a new level in the era of antibiotic resistance and human immunodeficiency virus infection . To date, no single antimicrobial is capable of eradicating the commonly encountered STD pathogens including Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum . Among the marketed fluoroquinolones, ciprofloxacin, ofloxacin, lomefloxacin, and enoxacin all provide excellent in vitro activity (MIC90 < 0.06 micrograms/ml) and excellent in vivo efficacy against N . gonorrhoeae, including multiply resistant isolates (penicillinase-producing N . gonorrhoeae and chromosomally mediated resistant N . gonorrhoeae) . Ofloxacin is the only fluoroquinolone approved by the Food and Drug Administration for chlamydial infection . All of the quinolones lack reliable in vitro activity against Ureaplasma urealyticum, a cause of nongonococcal urethritis . Although limited data suggest the usefulness of ciprofloxacin and ofloxacin in the treatment of pelvic inflammatory disease, these drugs cannot currently be recommended for single-agent therapy . Haemophilus ducreyi infections, however, can be managed effectively with the fluoroquinolones . Although their role continues to evolve, this class of drugs cannot be used equally to treat all STDs, and notably, no quinolone to date inhibits T . pallidum.

FEMS Microbiol Lett, 1993 May 1, 109(1), 85 - 91
Antigenic relationships of transferrin-binding proteins from Neisseria meningitidis, N . gonorrhoeae and Haemophilus influenzae: cross-reactivity of antibodies to NH2-terminal peptides; Griffiths E et al.; The NH2-terminal amino sequence through the first 20 amino acids was obtained for transferrin-binding protein (TBP)1 from three strains of Neisseria meningitidis . These were identical except for a glutamine to a glycine substitution at residue 6 in one case . The sequences of the NH2-terminal 20 amino acids of TBP2 from the same three strains were also determined; one TBP2 had a M(r) of 68,000 and the other two of 78,000 . Sequences were identical up to residue 13 in all three proteins . Peptides based on the NH2-terminal sequences of TBP1 and 2 were synthesized, linked to Keyhole Limpet haemocyanin and used to raise antibodies in rabbits . Anti-peptide antibodies cross-reacted on immunoblotting with the respective TBPs from all meningococcal strains tested, as well as with those from N . gonorrhoeae, suggesting that the NH2-terminals of these proteins are well conserved in the Neisseria . Neither anti-peptide serum reacted with the analogous TBP1 and 2 from Haemophilus influenzae, although common epitopes have previously been shown to exist.

Dtsch Tierarztl Wochenschr, 1993 May, 100(5), 185 - 8
Prophylactic application of Propionibacterium avidum KP-40 in swine with acute experimental infections . II . Bacterial infections: pleuropneumonia and swine erysipelas; Markowska-Daniel I et al.; The potent immunomodifier Propionibacterium avidum KP-40 (PA) demonstrated prophylactic potency in swine infected experimentally with Haemophilus (Actinobacillus) pleuropneumoniae or Erysipelothrix rhusiopathiae . Animals received PA either together with the respective vaccine or PA only; 3 resp . 4 weeks later all animals were inoculated with virulent pathogens . Eight of 10 swine immunized with inactivated pleuropneumonia vaccine developed mild-moderate forms of infection with temporary stagnation of body weight; application of the vaccine together with PA lowered the morbidity rate to 1 of 10 (p < 0.05) . Also in non-vaccinated swine infected with pleuropneumonia or erysipelas PA application resulted in milder clinical symptoms, faster recovery and a larger gain of body weight.

Rev Inst Med Trop Sao Paulo, 1993 May-Jun, 35(3), 259 - 69
{Brazilian purpuric fever, virulence in an animal model of Haemophilus aegyptius (H . influenzae biogroup aegyptius) . Grupo de Estudo da Febre Purpúrica Brasileira.}; Brandileone MC et al.; Brazilian purpuric fever (BPF) is caused by invasive strains of Haemophilus aegyptius (H . influenzae biogroup aegyptius, Hae) . These strains were differentiated from Hae strains associated only with conjunctivitis (non-invasive Hae strains) through specific molecular markers . Complement-depleted infant rat model was used to study the invasive and non-invasive Hae strains to compare their virulence potential . Inoculating 10(5) bacteria in the rats, the invasive strains caused 80 to 100% bacteremia and the intensity of bacteremia was 10(2.5 +/- 0.49) to > 10(4.69) cfu/ml of blood . Using the same infectious dose, the non-invasive strains did not cause frequent bacteremia (0 to 50%) and the intensity was 0 to 10(3.69 +/- 0.53) cfu/ml of blood . The infectious doses able to cause 50% of bacteremia in the rats (BD 50%) varied from < 10(3) to 10(4.2) bacteria for the invasive strains, whereas the BD 50% were 10(6.2) to > 10(7.3) bacteria for non-invasive strains . Passive immunization using antisera to invasive strains protected rats against bacteremia caused by homologous strains, but not by heterologous strain . By comparing the bacteremia caused by Hae and bacteremia caused by H . influenzae b (Eagan strain, Hib), it was demonstrated that Hib had higher virulence potential . This animal model was useful to clarify the virulence potential of invasive Hae strains.

Arch Fam Med, 1993 May, 2(5), 497 - 503
Cefaclor vs amoxicillin in the treatment of acute, recurrent, and chronic sinusitis; Huck W et al.; BACKGROUND: The treatment of acute, recurrent, and chronic sinusitis remains controversial because of the presence of a wide variety of aerobic and anaerobic bacteria in the sinuses . DESIGN: This double-blind, randomized trial compared cefaclor with amoxicillin in the treatment of acute, recurrent, and chronic maxillary sinusitis using clinical evaluation, roentgenography, and microbiologic evaluation of antral aspirates . SETTING: Outpatient office of five otorhinolaryngologists in Salt Lake City, Utah . PATIENTS: One hundred eight adult patients with acute, recurrent, or chronic maxillary sinusitis . INTERVENTION: Oral treatment with cefaclor (500 mg) twice daily or amoxicillin (500 mg) three times daily for 10 days . MAIN OUTCOME MEASURE: Clinical response to treatment with cefaclor vs amoxicillin . RESULTS: Fifty-six patients with acute sinusitis, 25 with recurrent sinusitis, and 15 with chronic sinusitis were evaluable . Although multiple organisms were common in each group, patients with acute sinusitis were more likely to have Haemophilus influenzae or Streptococcus pneumoniae, and patients with recurrent or chronic sinusitis were more likely to have anaerobes in sinus aspirate . Whether treated with cefaclor or amoxicillin, clinical improvement occurred in 86% of patients with acute sinusitis and 56% of patients with recurrent sinusitis . Patients with chronic sinusitis were too few to allow statistical analysis of the differences in outcome between them and patients with recurrent or acute sinusitis . Resistance of the cultured organisms to the study drug used was unrelated to treatment outcome . CONCLUSIONS: The rate of clinical improvement was high in patients with acute sinusitis but was less favorable in those with recurrent and chronic disease regardless of the study drug used . The susceptibility of organisms isolated to the study drugs was unrelated to outcome.

J Clin Microbiol, 1993 May, 31(5), 1111 - 6
Genetic characterization of a cryptic genospecies of Haemophilus causing urogenital and neonatal infections; Quentin R et al.; In recent years, reports originating from several areas of the world have identified biotype IV strains of Haemophilus influenzae as a cause of serious urogenital, neonatal, and mother-infant infections . Preliminary analysis of a sample of biotype IV isolates found evidence for a cryptic genospecies of Haemophilus (R . Quentin, A . Goudeau, R . J . Wallace, Jr., A . L . Smith, R . K . Selander, and J . M . Musser . J . Gen . Microbiol . 136:1203-1209, 1990) . Eighteen biotype IV strains assigned to the cryptic genospecies were further characterized by their rDNA restriction fragment length polymorphism patterns and genomic DNA-DNA hybridization . Isolates of the cryptic genospecies have distinctive rDNA restriction fragment length polymorphisms that differ from those of Haemophilus haemolyticus and H . influenzae . Genomic hybridization studies show that these organisms are allied with H . influenzae and H . haemolyticus and suggest a distant trifurcation of H . influenzae, H . haemolyticus, and the cryptic genospecies.

J Infect Dis, 1993 May, 167(5), 1106 - 11
Multistrain outbreak of chancroid in San Francisco, 1989-1991; Flood JM et al.; Restriction fragment length polymorphism (RFLP) and plasmid analyses were used to evaluate an outbreak of Haemophilus ducreyi in San Francisco . Fifty-four cases of culture-confirmed chancroid occurred between May 1989 and May 1991 . Of these, 46 (96%) were in men and 35 (65%) were in blacks; the median age of patients was 34 years . Among the 32 isolates submitted for RFLP and plasmid analyses, six different HindIII RFLP patterns were identified . Two RFLP types were found in patients who had recently traveled to Los Angeles, Korea, or El Salvador . Four RFLP types appeared to be acquired locally and were more common among blacks (P = .002), in patients with a history of a sexually transmitted disease (P = .01), and in those who used drugs or exchanged drugs or money for sex (P = .08) . The use of RFLP analysis confirmed that this outbreak was associated with multiple strains of H . ducreyi and allowed for the identification of risk factors for locally acquired chancroid.

Drugs, 1993 May, 45(5), 716 - 36
Loracarbef . A review of its antimicrobial activity, pharmacokinetic properties and therapeutic efficacy; Brogden RN et al.; Loracarbef is an orally administered member of a new synthetic class of beta-lactam antibiotics, the carbacephems, which is characterised by enhanced chemical stability . At low concentrations (< 2 mg/L) in vitro, it inhibits Streptococcus pneumoniae, S . pyogenes, beta-haemolytic streptococci groups B, C and G . Proteus mirabilis and Moraxella catarrhalis, including beta-lactamase-producing strains . At therapeutic plasma concentrations it is also active in vitro against most strains of Staphylococcus aureus, S . saprophyticus, Escherichia coli and beta-lactamase-positive and -negative strains of Haemophilus influenzae . Like other beta-lactams, loracarbef is inactive against methicillin-resistant strains of S . aureus . When administered at dosages of 200 to 400 mg twice daily, the clinical and bacteriological efficacy of loracarbef is comparable with that of amoxicillin and amoxicillin/clavulanic acid in patients with upper or lower respiratory tract infections, and comparable with that of cefaclor in treating infections of the lower respiratory tract, skin and skin structures and urinary tract . Loracarbef and phenoxymethylpenicillin (penicillin V) were equally effective in treating streptococcal pharyngitis and tonsillitis . Loracarbef is generally well tolerated by all age groups and causes less diarrhoea than amoxicillin/clavulanic acid . It is administered twice daily . It offers a suitable alternative to other orally administered antibiotics for the treatment of mild to moderate infections caused by susceptible organisms.

Infect Immun, 1993 May, 61(5), 1867 - 72
Identification of surface-exposed B-cell epitopes recognized by Haemophilus influenzae type b P1-specific monoclonal antibodies; Panezutti H et al.; A panel of P1 synthetic peptides was synthesized to map the surface-exposed epitopes of Haemophilus influenzae type b outer membrane protein P1 recognized by three murine monoclonal antibodies (MAbs 7C8, 3E12, and 6B1) . By using peptide-specific enzyme-linked immunosorbent assays, MAbs 6B1, 7C8, and 3E12 were shown to recognize distinct epitopes localized within residues 60 to 88, 165 to 193, and 400 to 437 of mature P1, respectively . Since MAb 7C8 was shown previously to be protective against certain H . influenzae type b subtypes in the infant rat model of bacteremia, its cognate epitope was further characterized by using truncated peptide analogs . Fine mapping of the 7C8 epitope by competitive inhibition studies revealed that it was localized within residues 184 and 193.

Lancet, 1993 Apr 3, 341(8849), 851 - 4
Population-based study of non-typable Haemophilus influenzae invasive disease in children and neonates; Falla TJ et al.; The extent of non-capsulate, non-serotypable Haemophilus influenzae (NST) as a cause of serious invasive disease in children has not been fully defined . We describe the epidemiology of these childhood infections from cases identified during a continuing prospective survey of invasive H influenzae disease in the Oxford region, UK . 408 strains of H influenzae were isolated from cases of invasive disease . 383 (94%) were H influenzae type b (Hib), 24 (6%) were NST strains, and 1 was a type f strain . 3 of the NST strains were non-capsulate type b mutants (b-), but the remaining 21 strains were from the phylogenetically distinct and heterogeneous population of non-capsulate H influenzae (NC) . 10 of the NC strains were isolated from neonates with sepsis; crude mortality rate was 40%, with an incidence of 4.6 cases per 100,000 livebirths . 11 NC strains were isolated from children after the neonatal period and under 10 years of age, 4 (36%) of which had severe, unrelated, predisposing conditions . The incidence of NC invasive diseases in these children was 0.5 per 100,000 per year . The attributable mortality for these infections was 10% . Infections due to these H influenzae strains are, after the implementation of Hib vaccines, likely to persist and represent a substantial proportion of the serious infections caused by this species.

Jpn J Antibiot, 1993 Apr, 46(4), 295 - 309
{Antimicrobial activities of aspoxicillin of fresh clinical isolates}; Deguchi K et al.; The Antimicrobial activity of aspoxicillin (ASPC) in terms of minimum inhibitory concentration (MICs) was compared with those of other penicillin antibiotics (PCs) against clinical isolates sent to us from medical institutions throughout Japan in 1988, 1990 and 1992 and strains isolated and identified from samples collected from patients with various infections . 1 . The MIC80's of ASPC against Staphylococcus aureus, Enterococcus spp., Escherichia coli, Bacteroides fragilis group were almost the same as those against these isolates in 1985 to 1986 . 2 . A trend for increasing susceptibility to PCs including ASPC was observed in the isolates of S . aureus and Haemophilus influenzae . This trend in S . aureus was attributed to the appearance of non beta-lactamase producing strains associated with the development of highly resistant strains among the methicillin-resistant S . aureus (MRSA) as well as to a tendency toward yearly decreasing frequency of MRSA . The trend for the increased susceptibility in H . influenzae was related to the decrease in the number of beta-lactamase production strains . 3 . The frequency of the strains highly resistant to PCs including ASPC increased . 4 . No PCs-resistant strains were observed among the so-called beta-streptococci, while among alpha-streptococci and Streptococcus pneumoniae there was a trend for decreasing frequency of strains with lower susceptibility to PCs or those with resistant to PCs . These strains may be variants which were also resistant to cephems and had penicillin-binding proteins (PBPs) . Meanwhile, a high frequency of highly PCs-resistant strains were noted among Enterococcus faecium . In view of the fact that the PCs-resistance of E . faecium is known to be related to PBPs, the pattern of the susceptibility of the recent clinical isolates to beta-lactams is considered to be multimodal.

J Antimicrob Chemother, 1993 Apr, 31(4), 543 - 57
An eight-year survey of the antimicrobial susceptibility patterns of 85,971 bacteria isolated from patients in a district general hospital and the local community; MacGowan AP et al.; Antimicrobial susceptibilities were determined for 85,971 bacteria isolated from clinical specimens in the microbiology department of a single district general hospital during the eight-year period between 1984 and 1991 . The isolates included 45,786 coliforms, 4483 Proteus spp . and 2644 Pseudomonas spp . from urine and 13,324 Staphylococcus aureus, 7311 beta-haemolytic streptococci, 4741 coliforms, 3643 Pseudomonas spp., 2778 Haemophilus influenzae, 638 Proteus spp . and 623 Streptococcus pneumoniae from other sites (excluding blood) . Patterns of susceptibility remained largely unchanged during the study period, except for a decline in the susceptibility of Proteus spp . to trimethoprim between 1984 and 1988 which had reversed itself by 1990 and a reduction in the susceptibilities of Pseudomonas spp . and S . aureus to ciprofloxacin between 1986 and 1991 . The susceptibilities of coliforms which had been isolated from sites other than the urinary tract to ampicillin, cefazolin and cefuroxime decreased between 1984 and 1988 but a more variable pattern was noted in subsequent years . Susceptibility of S . aureus to penicillin fell during the first five years of the study but has remained stable since . No change was observed in the susceptibility pattern of H . influenzae . In our experience, gentimicin-resistant Gram-negative bacilli, methicillin-resistant S . aureus and penicillin-resistant S . pneumoniae were rarely isolated.

Eur J Clin Microbiol Infect Dis, 1993 Apr, 12(4), 289 - 93
Serological cross-reactions between Moraxella (Branhamella) catarrhalis and other oropharyngeal bacteria; Jonsson I et al.; Oropharyngeal bacteria belonging to different species were tested for serological cross-reactions with Moraxella catarrhalis using sera from immunized rabbits . Sera were tested using immunofluorescence, an enzyme immunoassay (EIA) and immunoblotting . On immunofluorescence, significant cross-reactions were demonstrated with beta-hemolytic streptococci group A and group G, as well as with streptococci of the viridans group . Some cross-reactions were also noted with Neisseria meningitidis . In the EIA, strong cross-reactions were demonstrated with beta-hemolytic streptococci . No cross-reactions were obtained with Streptococcus pneumoniae, Haemophilus influenzae or common oral Neisseria . The results are of importance for the interpretation of serological tests to detect infections with Moraxella catarrhalis, and for the development of methods for detection of antigens in samples from the respiratory tract.

Nippon Jibiinkoka Gakkai Kaiho, 1993 Apr, 96(4), 674 - 84
{Role of surface tension lowering substances in the function of normal and diseased eustachian tubes of guinea pigs}; Kodama H et al.; To examine the role of surface tension lowering substances (STLSs), we measured changes in passive opening pressure (OP) and closing pressure (CP) in eustachian tubes of guinea pigs before and after washing the tubes with various solutions (saline solution, artificial pulmonary surfactant, synthetic phospholipids, and detergent)) . The percent decreases in OP and CP in tubes washed with artificial surfactant were significantly higher than those washed with saline solution . Those washed with synthetic phospholipids or detergent (Triton X-100) did not differ from those washed with saline solution . In guinea pigs with experimental otitis media produced by inoculation of formalin-killed Haemophilus influenzae into the middle ear cavity, the percent decreases in OP and CP in tubes washed with artificial pulmonary surfactant were significantly higher than in those washed with saline solution . Artificial pulmonary surfactant was injected into the middle ear cavity of the guinea pigs with otitis media . At 5 days after inoculation, the inflammatory changes of the middle ear were much milder in animals with intratemporal application of artificial pulmonary surfactant than in those with saline application . These results suggest the possible efficacy of treatment with artificial pulmonary surfactant for otitis media.

Antimicrob Agents Chemother, 1993 Apr, 37(4), 804 - 9
Ecology of Haemophilus influenzae and Haemophilus parainfluenzae in sputum and saliva and effects of antibiotics on their distribution in patients with lower respiratory tract infections; Foweraker JE et al.; Nine patients with lower respiratory tract infections were used to study in detail the effect of ampicillin or erythromycin on the colonization patterns of Haemophilus influenzae and Haemophilus parainfluenzae in sputum and saliva . H . influenzae was isolated from purulent sputum of eight patients before the start of treatment . Ampicillin was more effective than erythromycin at clearing H . influenzae from sputum and in decreasing purulence . By careful characterization of multiple strains, the changes in biotype distribution and antibiotic susceptibility patterns were shown . Five biotypes of H . influenzae were associated with chest infection, with type II predominating . Mixed biotype infections occurred in five patients . Most saliva contained multiple biotypes of H . parainfluenzae . Neither antibiotic selected resistant haemophili in saliva or sputum . After treatment with ampicillin, the mucoid sputum was colonized with ampicillin-susceptible H . parainfluenzae biotypes previously found in saliva . We postulate that as inflammation decreases at the bronchial mucosa, the ampicillin concentration drops, allowing ampicillin-susceptible oral H . parainfluenzae isolates to seed the residual mucoid sputum.

J Trop Pediatr, 1993 Apr, 39(2), 97 - 106
Bacterial aetiology of acute lower respiratory infections in pre-school Nigerian children and comparative predictive features of bacteraemic and non-bacteraemic illnesses; Johnson AW et al.; In a 9-month surveillance of the microbial agents causing acute lower respiratory infections (ALRI) in hospitalized preschool Nigerian children, 24 bacterial isolates were made from 22 (33 per cent) out of 66 blood cultures, including seven (70 per cent) of the 10 cultures from subjects with pleural effusion . Of the 24 positive isolates, Staphylococcus aureus accounted for 14 (58 per cent), Klebsiella pneumoniae for four (17 per cent), Streptococcus pneumoniae and Staphylococcus albus for two (8 per cent) each, and Haemophilus influenzae for only one case . Seven subjects had a mixed aetiology, comprising one bacteraemic case with measles and six with concomitant viral identifications . Sixteen cases, 10 (63 per cent) of whom were malnourished, had two or more pathogens, including 10 with multiple viruses . Bacterial isolates from the throat, were not significantly predictive of the ALRI aetiology . Overt malnutrition, empyema, and anaemia, were significantly commoner in bacteraemic cases (P < 0.03, 0.01, and 0.05), while rhinorrhoea and crepitations were each associated with the non-bacteraemic ones . (P = 0.05 and < 0.05) . A similar association was shown between rhinorrhoea, wheezing/rhonchi and the mixed aetiological group (P < 0.05 and 0.05, respectively) . The case-fatality in bacteraemic subjects, was 9 per cent and was 2.1 times higher than that for non-bacteraemic cases, in whom a shorter mean duration of admission was recorded . In developing countries, the need for periodic local surveillance of ALRI pathogens, as a prerequisite for evolving rational antimicrobial policies, is emphasized . Our findings underscore the predictive importance of malnutrition as a risk-factor of severe bacteraemic ALRI, frequently associated with multiple pathogens . The relative usefulness of blood culture in identifying bacterial agents of ALRI is discussed.

Recenti Prog Med, 1993 Apr, 84(4), 263 - 71
{Community-acquired bronchopneumonias in the elderly . The cost-benefit ratio in some plans of antibiotic therapy}; Scanelli G et al.; Community-acquired pneumonias represent the first cause of mortality due to a infectious disease, and determine more than 500,000 hospitalizations per year in the USA: moreover, they are the terminal event in many geriatric patients . Although the etiological microbial agents responsible for the majority of such pneumonias, Haemophilus influenzae and Streptococcus pneumoniae, are still sensitive to traditional antibiotics, as ampicillin, many doctors treat community acquired pneumonias with more recent and expensive antibiotics, as the third generation cephalosporins or other beta-lactamines, so enhancing the cost of the treatments, without a known, real advantage with respect to the older therapies . In this study, to evaluate whether the use of the latter antibiotics improves the outcome of community acquired pneumonias of the elderly with respect to the traditional therapy with ampicillin, we studied 123 hospitalized patients older than 65 years, affected by community-acquired pneumonia, simple or complicated . We also evaluated the cost/benefit ratio of every single treatment . Our data demonstrate that the recent antibiotics do not influence the outcome of the disease of the elderly: in particular, they do not affect the duration of the hospitalization, do not have a lower incidence of side effects, do not show a better efficacy versus ampicillin . The cost of the treatment with ampicillin is about one third of the cost of a third-generation cephalosporin treatment . We conclude that the treatment of choice for community acquired pneumonias of the elderly is ampicillin; only in few cases, as in nosocomial or in nursing homes pneumonias, third-generation cephalosporins or other antibiotics are necessary.

Pediatr Emerg Care, 1993 Apr, 9(2), 84 - 6
Correlating infectious outcome with clinical parameters of 1130 consecutive febrile infants aged zero to eight weeks; Bonadio WA et al.; The study objectives were to characterize the infectious outcomes and associated clinical parameters of a large group of febrile young infants who received outpatient sepsis evaluation . This retrospective review of consecutive cases during a seven-year period was set in an urban pediatric emergency department . Febrile infants, aged zero to eight weeks, were the participants . All received a standard evaluation for sepsis, including complete blood count/blood culture, lumbar puncture/cerebrospinal fluid culture, and urinalysis/urine culture . Of 1130 patients, 447 (42%) were aged zero to four weeks, and 683 (58%) were aged four to eight weeks . In 96 cases (8.5%), a bacterial pathogen was isolated by culture of cerebrospinal fluid, blood, urine, or stool; 58% were aged zero to four weeks and 42% were aged four to eight weeks . The rate of positive cultures per patient age was doubled in those aged zero to four weeks (12%) compared with those aged four to eight weeks (6%) . The 49 cases of invasive bacterial infections (bacterial meningitis/bacteremia) were most commonly associated with lower degrees of fever, as slightly over one half (25/49) had temperature < 39 degrees C . The most common pathogens of invasive bacterial infection were group B streptococcus and Escherichia coli, accounting for 33 of 49 cases (67%); the most common pathogens of invasive bacterial infection in older children (Haemophilus influenzae type b and Streptococcus pneumoniae) were relatively underrepresented, accounting for only five of these 49 (10%) cases.

Neonatal Netw, 1993 Apr, 12(3), 35 - 9
Prevention of childhood diseases through vaccination; Belcher EA; Many childhood diseases can be prevented by proper immunization . The purpose of this article is to provide information about the risks and benefits associated with vaccines used in the United States for children under one year of age . Vaccines can be made from live or killed organisms and can stimulate both local and systemic immunity . The immunization schedule recommended by the American Academy of Pediatrics is presented . Information about the use of routine vaccines, their risks and the diseases they prevent, is presented . Vaccines included are diphtheria, pertussis, tetanus, poliomyelitis, Haemophilus influenzae, influenza viruses and hepatitis B . Research is ongoing to develop new vaccines and improve those currently in use.

Epidemiol Infect, 1993 Apr, 110(2), 339 - 47
Effect of respiratory syncytial virus infection on binding of Neisseria meningitidis and Haemophilus influenzae type b to a human epithelial cell line (HEp-2); Raza MW et al.; It has been suggested that individuals might be more readily colonized with bacteria that cause meningitis through enhanced binding of the bacteria to virus-infected epithelial cells . As respiratory syncytial virus (RSV) affects infants and children in the age group also susceptible to bacterial meningitis, we tested the hypothesis that infection of HEp-2 cells by RSV might enhance binding of Neisseria meningitidis or Haemophilus influenzae type b (Hib) . Attachment of fluorescein-labelled bacteria to HEp-2 cells was measured by flow cytometry, and RSV-infected cells bound significantly more meningococci (P < 0.001) and Hib (P < 0.01) than uninfected cells . Although the isolates expressed different antigenic characteristics (3 meningococci and 5 Hib), all showed a similar pattern of binding . The results are discussed with reference to the methods used for detection of bacterial binding and to interactions that might explain the increased binding to RSV-infected cells.

Epidemiol Infect, 1993 Apr, 110(2), 307 - 16
Different seroprevalences of antibodies against Neisseria meningitidis serogroup A and Haemophilus influenzae type b in Sudanese and Swedish children; Salih MA et al.; Sampling of sera from 202 Sudanese and 124 Swedish children 1-14 years of age was conducted at the end of the 1980s presenting an opportunity to compare the seroprevalence of anti-Neisseria meningitidis (MC) serogroup A antibodies in an area immediately before outbreak of an epidemic (Sudan 1988) with a low endemic area (Sweden) . An ELISA antibody assay was developed for detection of antibodies against capsular polysaccharide of MC serogroup A and Haemophilus influenzae type b (Hib) . Serum antibody against MC serogroup A was found significantly more frequently in Sudanese than in Swedish children . This indicates that factors other than herd immunity, as measured by serum antibodies against MC serogroup A polysaccharide, are important for avoidance of an MC serogroup A epidemic . The seroprevalence of Hib antibodies was, in contrast, significantly higher in Swedish than in Sudanese children, especially for 5-9-year-old children . A possible explanation may be the different systems of day-care of children in the two countries.

J Bacteriol, 1993 Apr, 175(8), 2462 - 4
The dilution rate affects the outer membrane protein and lipopolysaccharide composition of Haemophilus influenzae type b grown under iron limitation; Langford PR et al.; When Haemophilus influenzae type b was grown under iron limitation in continuous culture, the dilution rate affected the outer membrane protein and lipopolysaccharide composition . Investigations of the effect of the reduced availability of iron or other environmental parameters on these surface components should be controlled for growth rate.

Proc Natl Acad Sci U S A, 1993 Apr 1, 90(7), 2875 - 9
High-molecular-weight proteins of nontypable Haemophilus influenzae mediate attachment to human epithelial cells; St Geme JW 3rd et al.; Nontypable Haemophilus influenzae are Gram-negative bacilli that represent a common cause of human disease . These organisms initiate infection by colonizing the upper respiratory tract . Despite the essential role of colonization, the bacterial determinants of this process remain poorly defined . We recently identified a family of surface-exposed high-molecular-weight proteins of nontypable H . influenzae that are related to filamentous hemagglutinin, a critical adherence factor of Bordetella pertussis . The genes encoding the two such high-molecular-weight proteins (HMW-1 and HMW-2) expressed by a prototypic nontypable H . influenzae strain have now been cloned and sequenced . In this study we examined the role of the HMWs in adherence to human epithelial cells . We found that loss of expression of HMW-1 by the prototypic strain and a HMW-1-like protein in a heterologous nontypable H . influenzae strain markedly decreased the capacity to adhere . The absence of expression of both HMW-1 and HMW-2 in the prototypic strain or their homologs in the second strain was associated with a further decrease in adherence . Expression of either HMW-1 or HMW-2 in nonadherent laboratory strains of Escherichia coli resulted in acquisition of the adherence phenotype . These results indicate that both HMW-1 and HMW-2 and the homologous proteins from a second strain can mediate attachment . We speculate that these proteins and the related proteins in other nontypable H . influenzae isolates are important colonization factors.

J Pediatr, 1993 Apr, 122(4), 517 - 23
Decreased Haemophilus colonization in children vaccinated with Haemophilus influenzae type b conjugate vaccine; Murphy TV et al.; OBJECTIVE: The incidence of invasive Haemophilus disease has unexpectedly decreased in unvaccinated children since the introduction of conjugate vaccine in the United States . The purpose of this study was to determine whether conjugate vaccination decreases colonization with Haemophilus influenzae type b . DESIGN: This study was a prospective, bimonthly survey of pharyngeal colonization with H . influenzae type b in children attending day care from October 1987 through September 1989 . Vaccination status was determined from the medical record . SUBJECTS: We obtained 1188 pharyngeal cultures from 283 healthy children, 18 to 59 months of age; 51 children had received unconjugated polysaccharide vaccine (PRP), and 89 had received conjugate vaccine (94% PRP-diphtheria toxoid) . MEASUREMENTS AND RESULTS: Multivariate analysis was used to test the possibility of an association between vaccination status and the rate of colonization with H . influenzae type b . Among children known to be exposed to at least one child with a positive culture result, the efficacy of conjugate vaccination to prevent H . influenzae type b colonization in an unmatched analysis was 64% (95% confidence interval: 5%, 86%; p = 0.02) and in a matched analysis 81% (95% confidence interval: 7%, 96%; p = 0.02) . No effect on colonization was found with PRP vaccination . CONCLUSIONS: Conjugate vaccination decreases H . influenzae type b pharyngeal colonization and thereby may decrease transmission of this agent among healthy children.

Genetics, 1993 Apr, 133(4), 755 - 61
Evolution of natural transformation: testing the DNA repair hypothesis in Bacillus subtilis and Haemophilus influenzae; Redfield RJ; The hypothesis that the primary function of bacterial transformation is DNA repair was tested in the naturally transformable bacteria Bacillus subtilis and Haemophilus influenzae by determining whether competence for transformation is regulated by DNA damage . Accordingly, DNA damage was induced by mitomycin C and by ultraviolet radiation at doses that efficiently induced a known damage-inducible gene fusion, and the ability of the damaged cultures to transform was monitored . Experiments were carried out both under conditions where cells do not normally become competent and under competence-inducing conditions . No induction or enhancement of competence by damage was seen in either organism . These experiments strongly suggest that the regulation of competence does not involve a response to DNA damage, and thus that explanations other than DNA repair must be sought for the evolutionary functions of natural transformation systems.

Infect Immun, 1993 Apr, 61(4), 1589 - 92
Neutralizing antibodies to Haemophilus ducreyi cytotoxin; Lagergard T et al.; Neutralizing antibodies against cytotoxin produced by Haemophilus ducreyi bacteria were studied in rabbits by an assay employing HEp-2 cells and diluted crude cytotoxin preparations from the organism . Antisera to 12 different H . ducreyi strains were prepared by immunization of rabbits with bacterial sonicates combined with Freund's adjuvant . The antibody response during infection with H . ducreyi was studied in two groups of rabbits which were infected with five live strains by either single or multiple intradermal injections . Neutralizing antibodies in hyperimmune sera to sonicates from 12 H . ducreyi strains tested against their homologous cytotoxin preparations were present with titers ranging from 1:80 to 1:640 . Similar antibody titers against heterologous cytotoxin preparations were recorded, indicating immunological similarity or identity between cytotoxins from the various H . ducreyi strains . Three strains did not produce cytotoxin, and these strains did not induce toxin-neutralizing antibodies . Hyperimmune sera to other gram-negative bacteria had no detectable neutralizing capacity, indicating species specificity of the H . ducreyi cytotoxin . Cytotoxin-neutralizing antibodies were not detectable in rabbit sera before infection with H . ducreyi . Repeated single injections with live bacteria resulted in development of low levels of neutralizing antibodies . Multiple primary injection of live bacteria of the cytotoxin-producing strain CCUG 7470 resulted in a low immune response to the cytotoxin preparation from the same strain . A booster infection resulted in the development of neutralizing antibodies in all rabbits infected with cytotoxin-producing strains . The antibody titers determined against the homologous cytotoxin preparation were similar to those recorded for two heterologous cytotoxin preparations.

Infect Immun, 1993 Apr, 61(4), 1559 - 62
Cloning and sequence analysis of the structural pilin gene of Brazilian purpuric fever-associated Haemophilus influenzae biogroup aegyptius; Whitney AM et al.; We have cloned and sequenced the Brazilian purpuric fever (BPF)-associated Haemophilus influenzae biogroup aegyptius (Hae) pilin gene . The sequence contained a 648-bp open reading frame encoding a mature pilin protein of 191 amino acids with a calculated mass of 20.5 kDa . There was 82% homology between the open reading frames of the BPF strain F3031 and H . influenzae type b (Hib) (strain M43) pilin genes and 71% homology at the amino acid level between the mature pilin proteins . However, areas of diversity were noted throughout the gene . A 17-bp probe corresponding to an area of diversity in the N-terminal region of the BPF-associated gene hybridized with other BPF strains but not with non-BPF Hae or Hib . In summary, the pilin protein of BPF-associated Hae is highly homologous to Hib pilin yet remains structurally distinct.

Infect Immun, 1993 Apr, 61(4), 1531 - 7
Antibodies to Haemophilus influenzae type b outer membrane proteins in children with epiglottitis or meningitis and in healthy controls; Johnson PD et al.; The two most common manifestations of Haemophilus influenzae type b (Hib) infection in Western communities are meningitis and epiglottitis . The role of antibodies against outer membrane proteins (OMP) in the pathogenesis of these diseases was investigated by Western blotting (immunoblotting) with an OMP antigen prepared from a local Hib strain . Acute- and convalescent-phase serum samples from 25 children with epiglottitis and 20 with meningitis and single serum samples from 19 control children in the same age group were tested . Western blots were evaluated quantitatively by use of graphs generated from a densitometer . OMP antibody was detected in all sera from patients and controls . There was no significant difference between the mean antibody level in acute-phase sera from children with meningitis (336 +/- 143 arbitrary units) and those from children with epiglottitis (286 +/- 134 arbitrary units) . However, the mean OMP antibody level in sera from healthy controls, with no known history of Hib disease, was significantly higher than that in sera from patients with Hib disease within 2 days of admission to the hospital (patients {n = 35}, 282 +/- 144; controls {n = 19}, 425 +/- 236; P = 0.007) . The difference was due mainly to higher levels, in control sera, of antibody against four proteins, one of which is either P1 or a comigrating protein of 49 kDa . The finding of higher levels of OMP antibody in healthy controls suggests a protective role for antibodies directed against one or more OMP . This information could be exploited in future vaccine development.

J Infect Dis, 1993 Apr, 167(4), 882 - 9
Tumor necrosis factor-alpha (TNF alpha) in cerebrospinal fluid from patients with meningitis of different etiologies: high levels of TNF alpha indicate bacterial meningitis; Glimaker M et al.; The levels of tumor necrosis factor (TNF)-alpha in cerebrospinal fluid (CSF) were analyzed in 139 patients with meningitis and in 20 control subjects . Elevated concentrations were observed in 42 (82%) of 51 patients with purulent bacterial meningitis (18/24 Haemophilus influenzae, 13/14 Streptococcus pneumoniae, 7/7 Neisseria meningitidis, and 4/6 with other purulent bacterial etiology) . In contrast, elevated levels were found in only 5 of 78 individuals with nonbacterial meningitis (2/8 with herpes simplex type 2, 3/3 with varicella-zoster virus) . Thus, the positive and negative predictive values were 0.89 for indicating a purulent bacterial meningitis . Raised CSF TNF alpha levels were observed in 7 of 8 patients with purulent bacterial meningitis in whom the routinely used parameters did not unequivocally indicate the diagnosis . Moderately increased levels were seen in 5 of 6 patients with Mycobacterium tuberculosis meningitis and in 1 of 4 cases of Borrelia burgdorferi . Thus, the present study indicates that concentrations of TNF alpha in CSF usually can discriminate between purulent bacterial and nonbacterial meningitis . These findings may contribute diagnostic guidance with routinely used CSF parameters.

Antimicrob Agents Chemother, 1993 Apr, 37(4), 885 - 8
Changes in adherence of respiratory pathogens to HEp-2 cells induced by subinhibitory concentrations of sparfloxacin, ciprofloxacin, and trimethoprim; Visser MR et al.; Preincubation with subinhibitory concentrations of sparfloxacin, ciprofloxacin, and trimethoprim decreased the adherence of the respiratory pathogens Klebsiella pneumoniae, Haemophilus influenzae, and Moraxella (Branhamella) catarrhalis to human larynx carcinoma HEp-2 cells . Subinhibitory concentrations of sparfloxacin did not change the adherence of Pseudomonas aeruginosa or Streptococcus pneumoniae 15.62, but adhesion of S . pneumoniae 15.42 was significantly enhanced by subinhibitory antimicrobial concentrations.

Epidemiol Infect, 1993 Apr, 110(2), 289 - 95
Non-radioactive ribotyping of Haemophilus ducreyi using a digoxigenin labelled cDNA probe; Brown TJ et al.; Haemophilus ducreyi, the causal organism of chancroid, has increased in significance recently due to its association with HIV transmission . Most previous typing systems have exploited phenotypic characteristics . Detection of ribosomal RNA cistrons, ribotyping, was successfully developed to examine H . ducreyi, but required the use of 32P . We have used digoxigenin to define ribotypes from 30 strains of H . ducreyi from diverse geographical locations . This was achieved by agarose gel electrophoresis of restriction enzyme (RE) digested DNA extracts . These extracts were vacublotted onto nylon membrane and probed using digoxigenin labelled complementary DNA probe, prepared from Escherichia coli 16S and 23S ribosomal RNA . From 19 REs tested, Ava II, Hinc II, Bgl II and BstE II gave clear ribotypes . The ribotypes of BstE II and Bgl II used together gave the highest index of discrimination (D = 0.95), 16 types, and showed good reproducibility . This non-radioactive method demonstrates the three important features of a typing system; discrimination, typability and reproducibility.

Avian Dis, 1993 Apr-Jun, 37(2), 574 - 6
Characterization of Haemophilus paragallinarum isolates from China; Chen X et al.; The biochemical and serological properties of 11 isolates of Haemophilus paragallinarum from outbreaks of infectious coryza in the People's Republic of China are described . All 11 isolates had the typical biochemical properties of H . paragallinarum, and all belonged to Page serovar A.

Avian Dis, 1993 Apr-Jun, 37(2), 310 - 4
Characterization of isolates of Haemophilus paragallinarum from Argentina; Terzolo HR et al.; The biochemical and serological properties of Haemophilus paragallinarum isolates recovered from 11 recent outbreaks of infectious coryza in layer hens and one case of swollen-head syndrome in broilers in Argentina are described . Twenty-four isolates had the typical biochemical properties of H . paragallinarum . All isolates were serotyped according to the Page scheme . Ten of the isolates were serovar A, 11 were serovar B, one was serovar C, and two isolates could not be serotyped . The isolates were also examined using a panel of monoclonal antibodies (MAbs) for Page serovars A (one MAb available) and C (three MAbs available) . The serovar B isolates all failed to react with any MAb . The serovar C isolate reacted with all three serovar C MAbs but not with the serovar A MAb . Only six of the 10 serovar A isolates reacted with the serovar A MAb . These results indicate that H . paragallinarum isolates from Argentina are antigenically distinct from those examined in other countries, and it is suggested that coryza vaccines intended for use in Argentina may be more effective if based on local strains.

Zhonghua Liu Xing Bing Xue Za Zhi, 1993 Apr, 14(2), 110 - 2
{A preliminary report on the preparation of antisera against Haemophilus influenzae}; Wu L; The antigenicity of 5 strains of serotype b Haemophilus influenzae was compared . Strain 58534 showed a higher titer than the rest four . Three lots of antisera were made by immunizing rabbits with 6 strains of Haemophilus influenzae . The results indicated that the antibody titer against strain 58534 also showed a higher level, and the titer only dropped by one dilution after stored in cool place for half a year . We considered that Haemophilus influenzae serotype b strain 58534 is a good strain for the preparation of antiserum against Haemophilus influenzae.

Br Med Bull, 1993 Apr, 49(2), 412 - 22
The immunocompromised traveller; Conlon CP; Increasing numbers of immunocompromised people are travelling abroad to areas where the risks of some infections are increased . HIV positive people respond reasonably well to most vaccines when asymptomatic but response is less predictable when symptomatic disease is present . Generally, live vaccines should be avoided in all stages of HIV disease . Patients with anatomic or functional asplenia are at particular risk of severe sepsis due to encapsulated bacteria and from malaria . They should be immunised against the pneumococcus, meningococcus, and haemophilus and should avoid travel to areas where the probability of malaria transmission is high . Patients receiving cancer chemotherapy or transplant recipients on long-term immunosuppression should avoid live virus vaccines but may benefit from bacterial polysaccharide vaccines such as the pneumococcal vaccine . All patients with potentially impaired immunity should be assessed on an individual basis in terms of the risks and benefits involved in travel and available prophylactic measures . Immunisations useful in their native regions can be reviewed at the same time . Such travellers should carry a physician's letter and contact address in case of medical problems encountered abroad.

Immunobiology, 1993 Apr, 187(3-5), 382 - 402
Lipo-oligosaccharides (LOS) of mucosal pathogens: molecular mimicry and host-modification of LOS; Mandrell RE et al.; Immunochemical studies of the lipo-oligosaccharides (LOS) of the Gram-negative bacteria Neisseria gonorrhoeae and Neisseria meningitidis have revealed some interesting structural characteristics of these LOS that might relate to their roles during pathogenesis . The carbohydrate moieties of the LOS of pathogenic Neisseria mimic carbohydrates present in glycosphingolipids of human cells . Firstly, an LOS component present among a number of Neisseria species is antigenically and/or chemically identical to lactoneoseries glycosphingolipids present in human cells . The lactoneoseries LOS becomes sialylated on Neisseria gonorrhoeae when they are grown in the presence of cytidine 5'-monophospho-N-acetyl-neuraminic acid (CMP-NANA), the nucleotide sugar for sialic acid . Examination of gonococci present in exudates from males with natural infection indicates that sialylation also occurs in vivo . The mechanism for this process apparently involves a bacterial sialyltransferase scavenging available host CMP-NANA ("host-modification" of LOS) and transferring the sialic acid to the lactoneoserieslike LOS . Strains of N . meningitidis and Haemophilus influenzae also express similarly sialylated LOS suggesting that this is a common mechanism of pathogenesis among these bacteria . Additional examples of LOS that mimic other glycosphingolipid series have been identified also and the fact that multiple series can be expressed in a single population of gonococci suggests that a diverse set of LOS can be presented to the host during infection . It is possible that this diverse set of LOS serve different functions for the bacteria in various hosts and/or environments during infection.

Comp Immunol Microbiol Infect Dis, 1993 Apr, 16(2), 123 - 30
Characterization of V factor-dependent organisms of the family Pasteurellaceae isolated from porcine pneumonic lungs in Spain; Gutierrez CB et al.; 116 V factor (NAD)-dependent strains belonging to the family Pasterurellaceae isolated from porcine pneumonic lungs were collected in Spain over a period of 1 yr and studied using 52 biochemical characters . In addition to Actinobacillus pleuropneumoniae (72 strains), Haemophilus taxon minor group (37 strains) and Taxon D (four strains), other taxon (three strains) were observed . This taxon, provisionally designated as Haemophilus sp . sorbitol+, is closed to A . pleuropneumoniae but differed by some biochemical characteristics . Among A . pleuropneumoniae strains, nine different serotypes were detected, the most frequent being serotypes 4 and 2.

J Infect Dis, 1993 Apr, 167(4), 962 - 5
Reactivity of antibodies against conserved regions of pilins of Haemophilus influenzae type b; Gilsdorf JR et al.; To identify epitopes on pilins of Haemophilus influenzae type b (Hib) that may also be immunologically available on assembled pili, antisera were developed against eight synthetic peptides that represent conserved and hydrophilic regions of Hib pilin . Seven of the eight peptides were immunogenic . Binding of the anti-peptide antibodies to purified pili of Hib strain Eagan was weak . However, when the purified pili were denatured by heating, binding of the anti-peptide antibodies improved considerably, suggesting that the epitopes defined by the peptides were more available for anti-peptide antibody binding on the denatured pilins than on purified pili . On Western blot analysis, strain variation was seen in the binding of some of the anti-peptide antibodies, notably those directed against peptides in the N-terminal half of the pilin . Thus, when pilins are assembled into pili, the epitopes defined by the seven immunogenic peptides appear to be altered so that binding of the anti-peptide antibodies is greatly reduced.

Am J Med, 1993 Mar 22, 94(3A), 85S - 88S
Fleroxacin in the treatment of chancroid: an open study in men seropositive or seronegative for the human immunodeficiency virus type 1; Tyndall MW et al.; Fleroxacin was prescribed to treat both HIV-negative and HIV-positive men with proven chancroid in an open study . HIV-negative men were treated with a single 400-mg dose of fleroxacin, and HIV-positive men were treated with 400 mg daily for 5 days . Three of the 58 evaluable HIV-negative men were clinical and microbiologic failures, and two of the 22 evaluable HIV-positive men had persisting infection with Haemophilus ducreyi . Both regimens were well tolerated . Fleroxacin is an acceptable alternative to existing treatment regimens for chancroid in men.

Am J Med, 1993 Mar 22, 94(3A), 131S - 135S
Efficacy of fleroxacin versus amoxicillin in acute exacerbations of chronic bronchitis; Chodosh S; In a multicenter study the efficacy and safety of oral fleroxacin at 400 mg once a day and amoxicillin at 500 mg three times daily for 7 days were compared for the treatment of patients with acute bacterial exacerbations of chronic bronchitis due to drug-susceptible bacteria . A total of 194 patients were enrolled, 102 in the fleroxacin group and 92 in the amoxicillin group . Of those enrolled, 22 in the fleroxacin group and 30 (29 for clinical efficacy) in the amoxicillin group were included in the efficacy analysis . All were included in the safety analysis . Clinical success was noted in 21 (95%) of 22 fleroxacin-treated patients and 22 (76%) of 29 amoxicillin-treated patients . Bacteriologic cure was obtained in 21 (95%) of 22 of the fleroxacin group and 18 (60%) of 30 of the amoxicillin group . One Haemophilus parainfluenzae strain persisted with fleroxacin . Persisting organisms with amoxicillin included Haemophilus influenzae (four), Haemophilus parainfluenzae (three), Escherichia coli (two), Streptococcus pneumoniae (one), Neisseria species (one), and Proteus mirabilis (one) . Adverse events were reported by 41% of 102 patients receiving fleroxacin and 15% of 92 patients receiving amoxicillin . Insomnia, dizziness, and nausea occurred more frequently with fleroxacin . Fleroxacin may be indicated for the treatment of acute bacterial infection in chronic bronchitis known to be due to Haemophilus species and Moraxella catarrhalis . The 92% incidence of resistance among the S . pneumoniae isolates recovered from all enrolled patients suggests that fleroxacin may not be useful for such infections.

J Immunol Methods, 1993 Mar 15, 160(1), 117 - 27
An efficient procedure for the generation of human monoclonal antibodies based on activation of human B lymphocytes by a murine thymoma cell line; Kwekkeboom J et al.; A new, efficient procedure for the generation of human monoclonal antibodies has been developed . The procedure is based on the activation of human B cells in microwells by murine thymoma EL4B5 cells . This mode of B cell stimulation leads to proliferation of at least one per eight of human B cells and to a high rate of antibody production . Subsequently, supernatants of the microwells are screened by ELISA for the presence of antibody of the desired specificity and B cells from selected wells are hybridized by electroporation . To optimize the procedure, the kinetics of the B cell expansion induced by EL4B5 cells were analysed . Counting and phenotyping of cultured cells at different time points indicated that the peak of B cell expansion occurred at day 5 for tonsil B cells (16-fold increase) and at day 7 for peripheral blood B cells (20-fold increase) . The B cells did not merely proliferate but also differentiated, as indicated by loss of CD20 expression and increase of CD38 expression . At the peak of B cell expansion, B cells could be hybridized efficiently with myeloma cells . The majority of the resultant hybridomas secreted human immunoglobulin . The efficiency of the procedure is exemplified by the generation of hybridomas secreting human IgG against Haemophilus influenzae from limited numbers of either human tonsil B lymphocytes or peripheral blood B lymphocytes.

FEMS Microbiol Lett, 1993 Mar 15, 108(1), 59 - 67
The ClpE protein involved in biogenesis of the CS31A capsule-like antigen is a member of a periplasmic chaperone family in gram-negative bacteria; Bertin Y et al.; The putative chaperone-like protein ClpE, required for biogenesis of the Escherichia coli capsule-like antigen CS31A, was compared with ten known periplasmic chaperones from E . coli, Klebsiella pneumoniae, Bordetella pertussis, Haemophilus influenzae and Yersinia pestis . The amino acid sequence alignment was superimposed onto the three-dimensional structure of the PapD chaperone of uropathogenic E . coli, and amino acid residues involved in maintaining the structure integrity of the suggested binding site were found identical in most of the 11 chaperones . Construction of a phylogenetic tree to investigate the relationship within the chaperone family has revealed interesting degrees of relatedness between the different proteins.

Pharmacoeconomics, 1993 Apr, 3(4), 286 - 308
Pharmacoeconomics of immunisation: a review; van den Oever R et al.; The effects of immunisation programmes that have existed for several decades in developed countries are demonstrated by the decrease and even eradication of smallpox, poliomyelitis, measles, mumps and hepatitis B . Cost, health policy and spontaneous evolution in the incidence of communicable diseases have a decisive influence on the use of a vaccine . Investment in vaccination policy has to be encouraged to maintain this progress made in the control of infectious diseases and to meet new challenges . Studies re-evaluating ongoing immunisation programmes are scarce . Nevertheless, it can be concluded that for vaccination against hepatitis B in professionally exposed at-risk populations, arguments for positive returns are consistent . The same holds for vaccination against S . pneumoniae and for influenza virus in the elderly . The results of the economic evaluation of revaccination against measles, when insufficient coverage exists, are inconclusive . Universal vaccination of children against Haemophilus influenzae type b (Hib) and of children of hepatitis B-positive mothers against hepatitis may require costs to be paid in order to gain extra health benefits.

Biochemistry, 1993 Mar 2, 32(8), 2003 - 12
Structural studies of the lipooligosaccharides from Haemophilus influenzae type b strain A2; Phillips NJ et al.; The outer membrane lipooligosaccharides (LOS) from Haemophilus influenzae type b strain A2 are a heterogeneous mixture of glycolipids containing a conserved Lipid A structure and a variable oligosaccharide moiety . After O-deacylation by treatment with anhydrous hydrazine, the O-deacylated LOS mixture was analyzed by electrospray mass spectrometry and shown to contain 11 components, ranging in M(r) from 2277.8 to 3416.4 . The majority of these structures contained a variable number of hexoses, three L-glycero-D-manno-heptoses, and one 3-deoxy-D-manno-octulosonic acid (KDO) residue attached to a diphosphorylated O-deacylated Lipid A moiety . Additional phosphate and phosphoethanolamine (PEA) groups were also present on the oligosaccharide structures . Two minor high molecular weight components were also observed that contained N-acetylhexosamine and sialic acid . Neuraminidase treatment of the O-deacylated LOS mixture resulted in the loss of sialic acid from these latter two species . After mild acid hydrolysis and separation by size-exclusion chromatography, liquid secondary ion mass spectrometry identified six major and four minor oligosaccharides, ranging in M(r) from 1243.4 to 2215.8 . These released oligosaccharides contained a common heptose trisaccharide core structure with anhydro-KDO at the reducing terminus, which arises as an artifact of the hydrolysis procedure by beta-elimination of a phosphate group from the 4-position of KDO . Selected oligosaccharide fractions were subjected to composition and methylation analyses and sequenced by tandem mass spectrometry . Taken together, these data defined the major O-deacylated LOS as follows: {formula: see text} Higher molecular weight structures in the mixture contained galactose, N-acetylglucosamine, and sialic acid as additional branch sugars, suggesting that H . influenzae A2 is capable of forming a sialylated lactosamine structure.

Eur J Clin Microbiol Infect Dis, 1993 Mar, 12(3), 215 - 7
An improved antiserum agar method for detecting carriage of Haemophilus influenzae type b; Barbour ML et al.; Enriched Columbia medium was tested against Levinthal medium for the isolation of Haemophilus influenzae type b . In both media, Haemophilus influenzae type b recovery and antigen-antibody precipitation halos were equivalent . Haemophilus influenzae type b colony size and iridescence were superior on enriched Columbia medium . Enriched Columbia medium is inexpensive, simply prepared and easily standardised.

Enferm Infecc Microbiol Clin, 1993 Mar, 11(3), 131 - 4
{Usefulness of the API ZYM system for the identification of Legionella sp.}; Pedro-Botet ML et al.; BACKGROUND: The identification of Legionella genus is usually difficult, time consuming, and expensive . We decided to study the usefulness of API-ZYM system (Biomerieux) for Legionella species identification . METHODS: A total of 96 strains (82 from Legionella genus and 14 from other bacterial genus) were included . We studied 19 different enzyme activities and we proceed following the manufacturers directions, with an incubation time for galleries of 4 hours at 37 degrees C . RESULTS: Seventeen out of the 19 enzyme activities were uniformly positive or negative for Legionella sp . Thus, the sensitivity of these activities was 100% in identifying Legionella sp . Valine and cystine-arylamidase gave variable reactions for Legionella sp . strains . When the results of these enzyme test were compared to those of the control strains (Haemophilus influenzae, Pseudomonas aeruginosa) we observed that alkaline phosphatase, esterase, esterase-lipase, acid phosphatase and naphthol-AS-BI-phosphohydrolase in one side and esterase, esterase-lipase and leucin-arylamidase in the other side were able to differentiate Legionella sp . strains from P . aeruginosa and H . influenzae, respectively . CONCLUSION: API SYM system is a simple, accurate and reproducible method for the identification of Legionella sp.

Stat Med, 1993 Mar, 12(5-6), 481 - 92
Monitoring of clinical trials and interim analyses from a drug sponsor's point of view; Williams GW et al.; This paper illustrates aspects of data monitoring of clinical trials in the pharmaceutical industry . Formal interim analyses are performed at least in part to address the question of whether the trial should proceed or whether there should be an early termination of the trial . For formal interim analyses, frequently independent data and safety monitoring committees are utilized for monitoring clinical trials, and adjustments to nominal significance levels for test statistics are required . Various statistical methods developed during the last fifteen years are utilized . Administrative interim analyses are those analyses that are performed without any intention to stop the trial as a consequence of those analyses . For administrative interim analyses, adjustments to significance levels may not be required, but results must still be carefully interpreted . Regardless of the interim analyses performed, it is critical that the plans for interim analyses be identified in the study protocol, and the dissemination of interim results be carefully restricted . The following clinical trials sponsored by Merck Sharp and Dohme Research Laboratories (MSDRL) will illustrate these points: CONSENSUS; CONSENSUS II; 4S; Haemophilus influenza type b efficacy trial; famotidine in upper gastrointestinal haemorrhage, and a phase II analgesic study . It is anticipated that data monitoring and interim analysis activities will increase for future clinical trials due to the availability of appropriate statistical methods and improved data management systems.

J Antimicrob Chemother, 1993 Mar, 31 Suppl C, 27 - 37
Dirithromycin disc susceptibility tests: interpretative criteria and quality control parameters; Barry AL et al.; Dirithromycin and its bioactive metabolite (erythromycylamine) were compared in vitro to erythromycin against 450 bacterial isolates . Dirithromycin and erythromycylamine did not differ in their in-vitro activity and the two compounds were additive when combined in equal proportions . Both compounds were active against erythromycin-susceptible bacteria but erythromycin was two to four times more potent on a weight-to-weight basis . Interpretive criteria for dirithromycin were not based on achievable blood concentrations since tissue concentrations may be 20-30 times greater than peak serum levels . Dirithromycin-susceptible strains were those with zones > or = 19 mm in diameter (15 micrograms dirithromycin disc) or MIC < or = 2.0 mg/L and resistance was defined as a zone < or = 15 mm or MIC > or = 8.0 mg/L . Interpretive criteria for testing Haemophilus influenzae on Haemophilus Test Medium (HTM) agar were not defined because of the drug's poor activity in the test system used . Two multi-laboratory studies were also undertaken, one to define quality control limits for disc diffusion tests and the other to define broth microdilution MIC control limits for tests with dirithromycin.

J Antimicrob Chemother, 1993 Mar, 31 Suppl C, 11 - 26
Comparison of macrolide antibiotics; Williams JD et al.; Macrolides have been in use since the early 1950s . In recent years new macrolides have been developed to try to overcome the problems associated with erythromycin . In general they have fairly similar in-vitro activity, although azithromycin has superior activity against Haemophilus influenzae and some Gram-negative organisms . Clarithromycin shows superior in-vitro activity against Legionella spp . and against the type strain of Chlamydia pneumoniae . The pharmacology of macrolides produces many interpretive problems, and macrolides show marked variation in their pharmacokinetic parameters, tissue affinity and intracellular penetration . Newer macrolides such as clarithromycin, roxithromycin, dirithromycin and azithromycin only need to be taken once or twice a day, which is likely to improve patient compliance . Few objective side-effect studies have been performed with the newer macrolides . Clinical efficacy studies are essential to elucidate the significance of the complex pharmacology of macrolides.

Acta Otolaryngol, 1993 Mar, 113(2), 191 - 5
Secretory IgA-, IgG- and C3b-coated bacteria in the nasopharynx of otitis-prone and non-otitis-prone children; Stenfors LE et al.; The proportions of secretory IgA (SIgA)-, IgG- and C3b-coated bacteria obtained from a well-defined area on the posterior wall of the nasopharynx (NPH) close to the Eustachian tube were determined . Samples taken from 25 otitis-prone (OP) and 25 non-otitis-prone (NOP) children with normal serum levels of IgA and IgG were evaluated using an immunofluorescence assay . Both groups harboured significantly more nasopharyngeal bacteria coated with IgG than with SIgA (p < 0.001) . The OP children had significantly fewer SIgA-coated bacteria (p < 0.05) but more C3b-coated bacteria (p < 0.01) in the NPH than the NOP children had . No significant difference was noted between the two groups regarding IgG coating . The occurrence of Branhamella catarrhalis in the NHP was more pronounced in the OP group (p < 0.05) . No significant differences in the occurrence of other middle ear pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus) or quantitative dominance of pathogens were noted between the two groups . Deficiency in SIgA coating of the nasopharyngeal bacteria may contribute to the otitis-prone condition.

Pharmacotherapy, 1993 Mar-Apr, 13(2 Pt 2), 45S - 50S
Diagnosis and treatment of community-acquired and hospital-acquired pneumonia; Foster MT Jr; The older drugs used to treat pneumonia may still be useful in self-limiting infections . Newer antibiotics--augmented penicillins, trimethoprim-sulfamethoxazole, third-generation cephalosporins, and others--are quite effective, but resistance can be a problem, and some patients cannot tolerate the adverse events associated with these agents . The fluoroquinolones are effective in treating pneumonia because of their broad spectra of activity against gram-negative and gram-positive organisms, including Streptococcus pneumoniae and Haemophilus influenzae . They are rapidly and nearly completely absorbed after oral administration; bioavailability ranges up to 100% for ofloxacin and lomefloxacin . Concentrations attained in lung tissues and sputum generally exceed the minimum inhibitory concentrations for the most common respiratory tract pathogens . The quinolones are also well tolerated; most adverse events are mild and do not lead to discontinuation of therapy . Ciprofloxacin and ofloxacin are available in parenteral as well as oral formulations . The high bioavailability of oral ofloxacin (> 95%) allows a patient to be started on the parenteral form in the hospital and continued taking the oral form at home with no loss of efficacy, but with reduced costs and improved quality of life.

J Infect, 1993 Mar, 26(2), 215 - 20
Haemophilus influenzae type b disease in north-west England; Quigley C et al.; A study was made in the north-west of England during 1989 in order to ascertain the incidence of serious Haemophilus influenzae infection, its short-term morbidity and certain characteristics of treatment . The incidence of culture-proven infection was 28 per 100,000 children under 5 years of age . Case fatality was 3%, one of the deaths being in a 6-year-old child . Some of the information obtained will help to assess the cost-effectiveness of the new vaccine to be administered to children in the U.K . The mean length of stay in hospital for all cases was 10 days . Of a total of 87 patients, 20 (23%) were admitted to an intensive therapy unit while five were transferred from a district general hospital to a regional paediatric unit . The estimated average cost per episode of acute care was 2700 pounds . Antibiotic regimens varied considerably.

Am J Prev Med, 1993 Mar-Apr, 9(2), 96 - 100
Development and validation of an immunization tracking system in a large health maintenance organization; Payne T et al.; Practitioners seeing individual patients and those charged with improving immunization practices in that population need accurate information on the epidemiology of immunizations within the population . To meet this need, we have developed a computer-based record of data required by the National Childhood Vaccine Injury Act of 1986 for all immunizations given to 350,000 enrollees in a large health maintenance organization . In the first eight months of operation, 102,271 immunizations representing 11 separate antigens given to 65,676 enrollees were entered into the database . Comparison of immunizations given and recorded in the medical record with the database shows that the system has high sensitivity, specificity, and positive predictive value, but a relatively low negative predictive value . The database is being used for analysis of current immunization practices for Haemophilus influenzae b vaccine and for research on adverse outcomes of childhood immunizations.

J Periodontol, 1993 Mar, 64(3), 162 - 8
Colonization of retrieved polytetrafluoroethylene membranes: morphological and microbiological observations; Tempro PJ et al.; Polytetrafluoroethylene membranes (ePTFE) used in guided tissue regeneration (GTR) are accessible to colonization by oral bacteria . The bacterial composition of the adherent biomass is unknown . We examined a total of 6 membranes that were retrieved after 4 to 6 weeks from human periodontitis sites, using optical and transmission electron microscopy (TEM) as well anaerobic cultivation . Five of the 6 membranes provided the microbiological data and microscopic data . TEM revealed an organized microbial mass covering the surfaces and also within the interstices of the open microstructure and occlusive portions of the membranes . Numerous bacterial forms including cocci, rods, and filaments with an interbacterial matrix, frequently in microcolonies, were identified . Anaerobic cultivation yielded Streptococcus and Actinomyces species with a minor component of Gram-negative facultative rods comprised mainly of Haemophilus species . Candida species was recovered from one membrane . These data show that ePTFE is heavily colonized by oral bacteria during retention . The impact of bacterial colonization of ePTFE is not known but it seems reasonable to assume that colonization of membranes may affect connective tissue regeneration . Further studies will be needed to examine the effect of systemic antimicrobials on ePTFE colonization and in turn to examine the effect on GTR.

Pediatr Res, 1993 Mar, 33(3), 307 - 11
Diversity of immunoglobulin light chain usage in the human immune response to Haemophilus influenzae type b capsular polysaccharide; Adderson EE et al.; The response to the capsular polysaccharide of Haemophilus influenzae type b (Hib PS) has been used to determine the molecular basis of antibody gene diversity in humans . In contrast to the relatively restricted nature of anti-Hib PS heavy-chain variable region gene expression, a variety of light-chain variable region genes may encode this antibody (Ab) response . Light-chain variable region gene usage appears to determine the expression of certain Ab idiotypes and fine antigen specificity . To further define the role of light-chain variable region gene usage in important anti-Hib PS Ab subgroups, we have cloned and sequenced a number of immunoglobulin light-chain variable region genes (IgVL) from human monoclonal IgA anti-Hib PS Ab generated in response to Hib PS-protein conjugate vaccines . Three of these Ab are encoded by unusual variable segments . One kappa-Ab is encoded by the "predominant" V kappa II A2 germline gene but, in contrast to a previously reported A2-encoded IgVL sequence, differs from the A2 germline sequence . The IgVL sequence of a second Ab is the only sequence of a kappa-Ab that cross-reacts with the structurally related antigen Escherichia coli K100 polysaccharide reported to date . This IgVL is encoded by a V kappa III-segment most closely homologous to the Humhv328/L16 germline gene, whereas previous reports suggested V kappa III-encoded anti-Hib PS Ab might be exclusively encoded by the germline gene Humhv325/A27.(ABSTRACT TRUNCATED AT 250 WORDS)

J Clin Microbiol, 1993 Mar, 31(3), 743 - 5
Biotypes and serotypes of Haemophilus influenzae from patients with meningitis in the city of São Paulo, Brazil; Landgraf IM et al.; A total of 1,094 Haemophilus influenzae isolates from cerebrospinal fluid were examined by biochemical and serological means . Most of them belonged to biotype I (70.9%) and to serotype b (99.4%) . The relationship of biotypes I and II to the ages of the patients was shown to be significant (P < 0.001).

J Clin Microbiol, 1993 Mar, 31(3), 512 - 7
Genomic fingerprinting of "Haemophilus somnus" isolates by using a random-amplified polymorphic DNA assay; Myers LE et al.; The random-amplified polymorphic DNA (RAPD) assay was used to generate DNA fingerprints for 16 isolates of "Haemophilus somnus," and one isolate each of "Haemophilus agni," "Histophilus ovis," "Actinobacillus seminis," Pasteurella haemolytica, and Escherichia coli . The RAPD assay differentiated among "H . somnus" isolates, which shared similarity coefficients of 0.46 to 1.00 on the basis of pairwise comparisons of RAPD markers produced with nine random decamer primers . Three virulent encephalitic "H . somnus" isolates exhibited identical banding patterns, suggesting a common clonal ancestry . The RAPD assay clearly distinguished between the "H . somnus"-"H . agni"-"H . ovis" group and the other bacterial species tested . The results of the present study suggest that DNA fingerprinting of "H . somnus" isolates by the RAPD assay could be valuable in revealing subspecific divisions within this largely unexplored species.

Ann Pharmacother, 1993 Mar, 27(3), 309 - 10
Ciprofloxacin-resistant Haemophilus influenzae infection in a patient with chronic lung disease; Barriere SL et al.; OBJECTIVE: To report a case of ciprofloxacin-resistant Haemophilus influenzae infection in a patient with chronic lung disease who was exposed to multiple courses of antimicrobial therapy . CASE SUMMARY: The patient suffered recurrent pulmonary infections and developed bronchiectasis as a consequence of longstanding, severe, combined immunodeficiency disease . He had received ciprofloxacin on several occasions for treatment and prophylaxis of recurrent pulmonary infections . On a recent admission his usual H . influenzae isolate, which had been highly susceptible to ciprofloxacin (minimum inhibitory concentration {MIC} < or = 0.06 mg/L) on previous admissions, was resistant to ciprofloxacin and ofloxacin (MIC 8 and 16 mg/L, respectively) . The patient responded to treatment with ceftizoxime and was discharged with oral cefixime, which was to be taken for a total of two weeks . DISCUSSION: Rare isolates of H . influenzae resistant to ofloxacin and lomefloxacin have been noted in Europe and Asia; however, none resistant to the fluoroquinolones have been previously reported in the US, and no resistance has been reported to ciprofloxacin . We believe that repetitive, cycling exposure to ciprofloxacin may have induced the resistance that developed in this patient's flora . CONCLUSIONS: Fluoroquinolones may be added to the list of drugs to which H . influenzae have become resistant . Only judicious use of these drugs will preserve their activity against important pathogens in community-acquired infections.

South Med J, 1993 Mar, 86(3), 329 - 33
Evaluation of cefixime in the treatment of bacterial maxillary sinusitis; Matthews BL et al.; The efficacy and safety of cefixime, the first oral third-generation cephalosporin, were evaluated in a multicenter clinical trial involving 118 adult patients with acute sinusitis or acute exacerbations of chronic sinusitis . Patients received a single daily dose of 400 mg of cefixime for a mean duration of 10 days; 106 patients completed a course of therapy . Clinical cure and improvement were achieved in 90% of these patients (61% cured and 29% improved) . Among the patients evaluated again 2 weeks after therapy, 91% had a sustained clinical cure or improvement . Sinus exudate specimens were obtained from all patients by transantral puncture before therapy . Pathogens were isolated from 76 patients (66%), the most common pathogens being Haemophilus influenzae, alpha-hemolytic streptococci, and Streptococcus pneumoniae . Eighty-six percent of pathogens were presumed eradicated . Three patients discontinued therapy because of side effects . The most frequently reported adverse effects were gastrointestinal, with 20% of patients reporting diarrhea . Cefixime was effective in the treatment of bacterial sinus infections in adults and was well tolerated.

Pediatr Infect Dis J, 1993 Mar, 12(3), 189 - 95
Preceding respiratory infection predisposing for primary and secondary invasive Haemophilus influenzae type b disease; Takala AK et al.; Cases (117) with invasive Haemophilus influenzae type b (Hib) disease and their family members reported symptoms of respiratory infection during the 4-week period before the onset of Hib disease significantly more often than age-, sex- and residence-matched controls (225) and their family members during the same time period . Viral (adenovirus; influenza A and B; parainfluenza types 1, 2 and 3; and respiratory syncytial virus) and Mycoplasma pneumoniae serology was performed in 84 paired sera from cases and 112 paired sera from controls, who were healthy children matched to the cases by age, year and season . Viral or M . pneumoniae infection was diagnosed equally often among cases and controls (18% for both groups) . However, patients who were associated cases of Hib disease (i.e . either the primary or secondary case of a case pair) had a diagnostic viral serology more often (50%) than did sporadic cases (13%) (odds ratio, 7.0; 95% confidence interval, 1.6 to 33; P = 0.006) . These results suggest that some infectious agent(s) caused symptoms among the patients and circulated among the patients' closest contacts immediately before their development of Hib disease and possibly predisposed for invasive Hib disease . For the development of associated Hib disease among close contacts of an index case, adenovirus, influenza A, respiratory syncytial virus or para-influenza type 1, 2 and 3 infections may be important.

J Clin Invest, 1993 Mar, 91(3), 788 - 96
Variable region expression in the antibody responses of infants vaccinated with Haemophilus influenzae type b polysaccharide-protein conjugates . Description of a new lambda light chain-associated idiotype and the relation between idiotype expression, avidity, and vaccine formulation . The Collaborative Vaccine Study Group; Granoff DM et al.; Haemophilus influenzae b polysaccharide (Hib PS)-protein conjugate vaccines differ chemically and immunologically . To determine whether anti-Hib PS variable region expression might differ according to vaccine formulation, infants were vaccinated at 2, 4, and 6 mo of age with Hib PS coupled to either meningococcal outer membrane protein complex (Hib PS-OMPC) or tetanus toxoid (Hib PS-T), or Hib PS oligomers coupled to a mutant diphtheria toxin (Oligo-CRM) . Two anti-Hib PS idiotypes were measured in sera obtained after the third injection: HibId-1, expressed by anti-Hib PS antibodies having the kappa II-A2 variable region, and HibId-2, a newly defined cross-reactive idiotype associated with a subset of anti-Hib PS antibodies having lambda VII variable regions . HibId-1 was present in 33, 68, and 64% of infants given either Hib PS-OMPC, Oligo-CRM, or Hib PS-T, respectively (P < 0.001) . The respective values for HibId-2 were 47, 18, and 10% (P = 0.001) . Subjects who were vaccinated with Hib PS-OMPC or Hib PS-T and who produced detectable HibId-1-positive antibody, had significantly higher mean antibody avidity than subjects who did not produce HibId-1 positive antibodies . In contrast, Oligo-CRM evoked high avidity anti-Hib PS antibodies, irrespective of the idiotypic profile . These findings indicate fundamental differences in both variable region content and antibody quality elicited by different Hib PS conjugate vaccines.

J Pediatr, 1993 Mar, 122(3), 410 - 3
Responses of children to booster immunization with their primary conjugate Haemophilus influenzae type B vaccine or with polyribosylribitol phosphate conjugated with diphtheria toxoid; Decker MD et al.; Children primed with one of four conjugate Haemophilus influenzae type b vaccines received booster immunization with their primary vaccine or with polyribosylribitol phosphate conjugated with diphtheria toxoid . The latter vaccine produced postbooster antibody levels that equaled or exceeded those produced by boosting with the original vaccine, and thus may be used as a booster irrespective of the original vaccine.

J Infect Dis, 1993 Mar, 167(3), 642 - 50
In vitro model of Haemophilus ducreyi adherence to and entry into eukaryotic cells of genital origin; Lammel CJ et al.; Electron microscopy was used to examine Haemophilus ducreyi adherence to and entry into eukaryotic cells of genital origin . A clinical H . ducreyi isolate (90-244) adhered in snake-like whorls to the surfaces of cervical carcinoma cells (HeLa 229), endometrial adenocarcinoma cells (HEC-1-B), and human neonatal foreskin fibroblast (HFF) cells . A prototype strain of H . ducreyi (CIP542) adhered in randomly organized clumps on the surfaces of HFF . Strain 90-244 entered HFF and HEC-1-B cells but did not enter HeLa cells . The H . ducreyi in the HFF cells at 2 h were partly surrounded by a membrane consistent with that of a phagocytic vacuole . At 2 h, strain CIP542 was found in interstitial spaces between the HFF cells and also in the cytoplasm of the cells . After 7 and 24 h, both strains of H . ducreyi were found in the large interstitial spaces between the HFF cells, in the cytoplasm, and extracellularly . This model of in vitro H . ducreyi infection of eukaryotic cells will allow for more specific study of factors that determine the virulence of H . ducreyi.

J Immunol, 1993 Mar 1, 150(5), 2056 - 61
Age-dependent V region expression in the human antibody response to the Haemophilus influenzae type b polysaccharide; Lucas AH et al.; The human L chain antibody repertoire specific for the Haemophilus influenzae type b (Hib) polysaccharide (PS) is composed of kappa I, kappa II, kappa III, kappa IV, and lambda L chain V regions, but the most commonly occurring VL is encoded by the unmutated V kappa II-A2 gene . To determine whether this VL repertoire is influenced by age, we used idiotypic probes to monitor V kappa II-A2, V lambda, and V kappa III usage in the antibody response to an Hib PS-protein conjugate vaccine . A single dose of a vaccine consisting of Hib PS coupled to an outer membrane protein complex of Neisseria meningitidis was administered . Adults (n = 35), 18-month-old infants (n = 35), and 2-month-old infants (n = 46), all with > or = 0.9 microgram/ml anti-Hib PS antibodies, were tested for VL region markers in postvaccination sera . V kappa III anti-Hib PS antibodies were not detected in any of the 2-month-old infants but were detected in 29% of the 18-month-old infants and 69% of the adults (p < 0.001) . The lack of kappa III antibodies in 2-month-old infants could not be accounted for by lack of a kappa response, because kappa antibodies to Hib PS were present (> 0.15 microgram/ml) in 45% of these infants . Hibld-1, an idiotope expressed by anti-Hib PS antibodies having the kappa II-A2 V region, was present in postvaccination sera of 66% of the adults and 80% of the 18-month-old infants but was less frequent in the 2-month-old infants (35%, p < 0.001) . In contrast, Hibld-2, which is an idiotope expressed by a subset of V lambda VII anti-Hib PS antibodies, was rare or infrequent in adults and 18-month-old infants (0% and 6%, respectively) but was present in 43% of 2-month-old infants (p < 0.001) . Our findings demonstrate that dramatic changes in VL region utilization occur in the human antibody response to this Hib PS conjugate vaccine as a function of age . Because previous studies have shown that V region usage correlates with antibody fine specificity and avidity for Hib PS, these age-related differences in V region expression may affect the ability of vaccines to confer protective immunity at different ages.

J Clin Microbiol, 1993 Mar, 31(3), 751 - 3
Susceptibility of Haemophilus influenzae to piperacillin-tazobactam combinations: interpretive criteria and quality control limits for standardized tests; Barry AL et al.; In vitro studies evaluated methods for testing the susceptibility of Haemophilus influenzae to piperacillin-tazobactam combinations . Ampicillin-resistant beta-lactamase-nonproducing strains of H . influenzae may be presumed to be relatively resistant to combinations of piperacillin-tazobactam, even though they frequently appear to be susceptible by disk diffusion methods . Other ampicillin-resistant or -susceptible strains were predictably susceptible; i.e., 130 such strains gave zones of inhibition > or = 26 mm in diameter, and MICs for these strains were < or = 0.125/4.0 micrograms/ml (< or = 1.0/0.12 micrograms/ml when an 8:1 ratio was tested) . A resistant category has yet to be defined . For quality control purposes, H . influenzae ATCC 49247 should give zones of inhibition 32 to 38 mm in diameter, and broth microdilution MICs should be 0.12/4.0 to 0.5/4.0 micrograms/ml.

Semin Respir Infect, 1993 Mar, 8(1), 3 - 13
Infectious diseases that result in slowly resolving and chronic pneumonia; Corley DE et al.; Familiarity with the natural history of common pneumonias is obligatory for the clinician to determine whether a specific case of pneumonia is resolving at the expected rate . To many clinicians, the term slowly resolving pneumonia conjures an association with underlying neoplasm and/or less common pathogens . In reality, host factors or common pathogens such as Streptococcus pneumoniae and Legionella pneumophila are more likely responsible for delayed resolution . Familiarity with the pattern of resolution of pneumonias caused by these organisms should allow the clinician to follow such patients and avoid premature invasive evaluation . In contrast, Mycoplasma pneumoniae and Chlamydia species rarely result in slowly resolving pneumonia . Chronic bacterial pneumonia is an infectious syndrome that may present in the absence of systemic symptoms . The presentation is varied and may mimic neoplasm, interstitial lung disease, or chronic fungal or mycobacterial infection . Bacteria most commonly associated with chronic pneumonia include Haemophilus influenzae, Staphylococcus aureus, alpha-hemolytic streptococci (not S pneumoniae), and Pseudomonas aeruginosa.

Infect Immun, 1993 Mar, 61(3), 1132 - 5
Effect of modulation of polymorphonuclear leukocyte migration with anti-CD18 antibody on pathogenesis of experimental otitis media in guinea pigs; Patel J et al.; Guinea pigs were treated with anti-CD18 antibody (M8), and subsequently middle ears (ME) were infected with nontypeable Haemophilus influenzae . Forty-eight hours after infection, the ME washes of these animals had significantly lower polymorphonuclear leukocyte numbers but higher bacterial counts compared with washes of animals treated with control antibody (M11) or saline . The edema and epithelial damage of ME tissues correlated directly with polymorphonuclear leukocyte numbers and not bacterial counts.

Lancet, 1993 Feb 27, 341(8844), 511 - 4
Prospective study of aetiology and outcome of adult lower-respiratory-tract infections in the community; Macfarlane JT et al.; Community-acquired adult lower-respiratory-tract infections (LRTI) are generally thought to be caused by atypical and viral infections . We have studied 480 adults presenting to a single general practice with community-acquired LRTI between November, 1990, and December, 1991 . The overall incidence was 44 cases per 1000 population per year; the incidence was 2-4 times higher in people aged 60 and over than in those aged less than 50 . 206 patients were studied in detail; among this group 91 (44%) had 113 pathogens identified . There were 92 bacteria (Streptococcus pneumoniae in 62 and Haemophilus influenzae in 16), 19 viruses (influenza virus in 12), and only 2 atypical pathogens (Mycoplasma pneumoniae and Coxiella burnetii) . Pneumococcal infection was common in people who were 60 or older, those who had underlying chronic disease, or people with both features . There was moderate morbidity in terms of time in bed, time to return to normal activities, and days off work . 25% of patients returned for a second consultation with the general practitioner, in most because of unsatisfactory clinical progress . Community-acquired LRTI are very common, and the range of causative pathogens is similar to that for community-acquired pneumonia . Existing management strategies seem inadequate.

Clin Lab Sci, 1993 Mar-Apr, 6(2), 85 - 9
Sexually transmitted diseases: risks, transmission, and laboratory diagnostic update; Kwa B et al.; Sexually transmitted diseases (STDs) are a major public health problem of the 1990s . In the pre-antibiotic era, these infections were often fatal . The 1960s saw an alteration in public attitudes toward sexual practices and a resultant increase in the incidence of STDs . Today, despite increased efforts in health education and the encouragement of "safe sex" practices, the incidence of STDs continues to rise . Infection control is complicated by the frequent lack of symptoms of many STDs . This article will discuss only the most common STDs in the United States . These include those caused by the organisms Neisseria gonorrhoeae, Herpes simplex virus, Chlamydia trachomatis, Treponema pallidum, Haemophilus ducreyi, and Hepatitis B virus.

Oral Microbiol Immunol, 1993 Feb, 8(1), 36 - 41
Microbiology of early supragingival plaque development after delmopinol treatment; Collaert B et al.; The aim of this double blind, cross-over, microbiological study was to compare the effect of topical application of the plaque control agent 0.5% delmopinol HCl with placebo on early supragingival plaque formation . Six subjects underwent 7 periods (0.5, 1, 2, 8 and 24 h and 3 and 7 days) of placebo and delmopinol application, respectively . At the start of each study period the teeth were professionally cleaned and 2 ml of placebo and delmopinol 0.5%, respectively, were applied on all teeth (twice daily for periods lasting 24 h or more) . At the end of each period, supragingival plaque samples of one upper and one lower buccal tooth surface were collected separately and cultured on anaerobically incubated Brucella blood agar, on aerobically incubated blood agar and on selective media for the enumeration of Streptococcus spp., Haemophilus spp., Actinomyces spp., Veillonella spp., Neisseria spp . and Fusobacterium spp . The total anaerobic cultivable microflora after delmopinol use was 10-100 times lower than after placebo use . Compared with placebo, the proportion of cultivable aerobes (61.3%), Streptococcus spp . (104.8%) and Haemophilus spp . (82.3%) increased and the proportion of Actinomyces spp . (86.1%), Veillonella spp . (60.5%), Neisseria spp . (96.9%) and Fusobacterium spp . (60.6%) decreased after 7 days . Short-term application of 0.5% delmopinol HCl on supragingival dental plaque regrowth resulted in a reduction of the number of cultivable microorganisms in the plaque and produced a shift in the cultivable plaque composition.

Leuk Lymphoma, 1993 Feb, 9(3), 177 - 92
Active immunization of children with leukemia and other malignancies; Ridgway D et al.; Active immunization against measles, Haemophilus influenza B, tetanus, diphtheria, hepatitis B, influenza, poliomyelitis, and, when indicated varicella and pneumococcus induces long-lasting immunologic protection in most healthy pediatric vaccine recipients . Among children receiving immunosuppressive therapy for cancer, possible early loss of specific immunity acquired from prior vaccination or disease, and likely diminished responsiveness to initial or booster vaccination must be considered . In addition, the safety of vaccine administration requires separate study in this population . Published evidence demonstrates preservation of vaccine-induced antibody titers against tetanus, diphtheria, poliomyelitis and (in children treated for lymphoma) pneumococcus . In contrast, prior immunity to varicella, influenza, and hepatitis B (when naturally acquired), and measles (acquired by vaccination) is compromised during and/or after antineoplastic therapy . Studies of immunologic protection acquired by prior vaccination against hepatitis B, varicella, and H influenza have not been published . The safety of administering toxoids and inactivated vaccines in this population is well documented . In contrast, morbidity must be expected if live attenuated vaccines (oral polio vaccine, attenuated measles vaccine or attenuated varicella vaccine) are administered to children receiving anti-cancer therapy . The risks of using live vaccines should be measured against demonstrable benefits in any vaccine program . The response to initial or booster immunizations against tetanus and diphtheria are similar to those in healthy children . For all other immunizations reviewed, responsiveness is diminished during periods of chemotherapy, more strikingly in children treated for leukemia than for solid tumors . Antibody responses to these vaccines range from slightly blunted (in the case of H influenza B) to marginal (influenza) or completely useless (pneumococcus and hepatitis B in children treated for leukemia).

Vet Microbiol, 1993 Feb, 34(2), 191 - 7
Purification of hemagglutinin from Haemophilus paragallinarum using monoclonal antibody; Takagi M et al.; The purification of hemagglutinin from Haemophilus paragallinarum was attempted using affinity chromatography with monoclonal antibody . The antigen eluted from the affinity column using potassium thiocyanate buffer agglutinated chicken erythrocytes . In immunoblotting of the eluted antigen, a single band with monoclonal antibody was found as well as the crude antigen . When the chickens were immunized with the eluted antigen, they produced the hemagglutination inhibition (HI) antibody, and they showed protection against challenged exposure with H . paragallinarum strain 221 . These results indicated that the HA antigen of H . paragallinarum was a protective antigen.

Scott Med J, 1993 Feb, 38(1), 18 - 20
Epidemiology of Haemophilus type b invasive disease in childhood in Glasgow; Coggins A et al.; The objective of this study was to investigate the epidemiology of invasive disease due to Haemophilus influenzae type b in childhood in Glasgow . A retrospective study has been made on the hospital records of 252 children aged 0 to 12 years admitted to Glasgow hospitals during 1981-1990 . The annual incidence of invasive Haemophilus influenzae type b disease in Glasgow was estimated at 39 per 100,000 children less than five years of age per year . The figure for Haemophilus meningitis was 23.8 per 100,000 children less than five years of age per year . Ninety-five per cent of all cases occurred in children less than five years of age and 72.1% of meningitis cases occurred before two years of age . There was a mortality of 2.77% . Long-term neurological sequelae were found in 15.3% of the survivors . The annual incidence of Haemophilus influenzae type b disease is slightly higher in Glasgow than previously reported for the United Kingdom . The study provides baseline data to help assess efficacy of proposed early childhood vaccination.

J Antimicrob Chemother, 1993 Feb, 31 Suppl B, 93 - 9
Current and future trends in immunization against meningitis; Jones DM; The progress in vaccines for Haemophilus influenzae type b infection is followed; it is the disadvantages of pure polysaccharide vaccines that have stimulated the development of the present generation of polysaccharide-protein conjugated vaccines . From extensive clinical trials it is apparent that these are very effective in preventing disease in children . Conjugated haemophilus vaccines were introduced into the routine immunization schedules in the UK in Autumn 1992 . Meningococcal A and C polysaccharide vaccines, effective for epidemic disease, are only now being developed in a protein conjugated form with the prospect of protecting young children and producing durable immunity . Group B outer membrane-based meningococcal vaccines produce only a low degree of protection and much further work is needed before even the optimum vaccine constituents of this organism can be identified . Vaccines to replace multivalent pneumococcal polysaccharide mixtures are only in the very earliest stages of development.

J Antimicrob Chemother, 1993 Feb, 31 Suppl B, 79 - 91
Chemoprophylaxis of bacterial meningitis; Cuevas LE et al.; Bacterial meningitis continues to be a life-threatening disease and an important cause of severe disability in otherwise healthy individuals . This article reviews the aspects related to the prevention of secondary cases . Our understanding about the factors leading to an epidemic and the identification of high risk groups remains limited . For this reason, chemoprophylaxis can be used only for the prevention of secondary cases once an index case has been identified . The objectives of prophylaxis are threefold: (i) to eliminate nasopharyngeal carriage in household contacts; (ii) to prevent contacts from acquiring the disease and (iii) to treat infection in those incubating the disease . Chemoprophylaxis can only achieve the first of these objectives . Nasopharyngeal carriage of meningococci and Haemophilus influenzae can be eradicated with the use of antibiotics and their advantages and disadvantages are discussed . Prophylaxis should be given to household members and kissing and saliva-exchanging contacts of a case of meningococcal meningitis . The decision to give prophylaxis to extended family contacts, close neighbour contacts or children attending day-care centres where a case has occurred is controversial . It does not alter the course of an epidemic and close contacts are liable to become reinfected soon after prophylaxis . Prophylaxis of H . influenzae should be given to households in which there is at least one child (other than the index case) under 48 months of age . There is no agreement on the need to provide chemoprophylaxis to children in day-care centres because the risk of secondary infections is uncertain . An alternative to chemoprophylaxis is protective chemotherapy which can prevent the development of meningitis in individuals incubating the disease.

J Pediatr, 1993 Feb, 122(2), 212 - 8
Antibody response to outer membrane protein of nontypeable Haemophilus influenzae in otitis-prone children; Yamanaka N et al.; One of the major outer membrane proteins of nontypeable Haemophilus influenzae, P6, is highly conserved among strains, serves as a target for bactericidal antibody, and has been proposed as a possible vaccine candidate . The serum antibody response to P6 was studied in otitis-prone and normal children by an enzyme-linked immunosorbent assay . Of 20 otitis-prone children, 12 (60%) had a serum IgG antibody response to P6 after otitis media; however, the mean acute antibody level for the group, 4.6 micrograms/ml, was not significantly different from the convalescent level, 5.4 micrograms/ml . Anti-P6 antibody levels were also measured longitudinally for 10 to 25 months in 30 otitis-prone and 13 healthy children . Antibody levels increased sevenfold in the normal group compared with less than three-fold for the otitis-prone group and were significantly higher in the normal children after the age of 18 months (p < 0.05) . Finally, otitis-prone children who had two or more episodes of otitis media with nontypeable H . influenzae did not have an anamnestic antibody response to P6 . The failure to recognize P6 as a specific immunogen may account for recurrent infections . Moreover, the data suggest that otitis-prone children may not respond adequately to a vaccine containing P6.

Clin Exp Immunol, 1993 Feb, 91(2), 337 - 41
Percentile ranges for serum IgG subclass concentrations in healthy Chinese children; Lau YL et al.; In order to establish normal reference ranges of serum immunoglobulin G subclasses for different age groups in Chinese, we measured the four IgG subclasses by radial immunodiffusion using polyclonal antisera in 350 normal healthy subjects (148 males and 202 females) recruited from the community . There was no significant sex difference for all the four IgG subclasses . Using Box-Cox transformation, we constructed smooth age-dependent percentile curves for the four IgG subclasses . For the 50th percentile values, the plateaus for IgG1 to IgG4 are respectively 970 mg/dl at 13 years old, 481 mg/dl at 18, 48 mg/dl at 17 and 80 mg/dl at 13 . Methodology, reagents, environmental and genetic factors might be responsible for the observed difference among the various reports . The IgG2 level in our Chinese population seemed to be higher than that in Caucasians, which might account for the very low incidence of invasive Haemophilus influenzae type b disease among the Chinese . Our IgG1 level also plateaued later and at a higher level than that in other studies.

Pediatrics, 1993 Feb, 91(2), 451 - 5
Serum bactericidal test as a prognostic indicator in acute pulmonary exacerbations of cystic fibrosis; Cahen P et al.; The serum bactericidal test has been used for many years for optimal assessment of the efficacy of antibiotic therapy in patients with infective endocarditis and other bacterial infections . Its capacity to predict the bacteriological outcome of acute pulmonary exacerbations in patients with cystic fibrosis was evaluated . A total of 54 courses of intravenous antibiotic therapy were analyzed in 22 patients, whose ages ranged from 4 months to 24 years (mean age: 10 years) . The serum bactericidal activity of blood samples, taken at expected peak and trough antibiotic levels on day 4 of therapy, were determined against the potentially pathogenic strains isolated in sputum at the time of admission . For 104 isolates (64 Pseudomonas aeruginosa, 28 Staphylococcus aureus, and 12 Haemophilus influenzae strains), the peak and trough bactericidal titers were compared to bacteriological outcome . Bacteriological success was defined as a decrease of 2 log10 units or more in the bacterial density in sputum between days 0 and 7 of therapy . At peak antibiotic levels, serum bactericidal titers of 1:128 or more were 96% (all isolates) and 89% (P aeruginosa isolates), predictive of cure, whereas serum bactericidal titers of less than 1:16 were 100% predictive of failure for all infecting bacteria . In patients aged less than 18 years, the best peak titer for predicting success was 1:64, with a predictive value of 96% for titers of 1:64 or greater . The peak titer that best predicted success in patients aged 18 years or more was 1:128, with a predictive value of only 83% for titers of 1:128 or greater.(ABSTRACT TRUNCATED AT 250 WORDS)

J Infect Dis, 1993 Feb, 167(2), 464 - 8
The biologic activities of peptidoglycan in experimental Haemophilus influenzae meningitis; Burroughs M et al.; While gram-positive bacterial cell walls are known to incite inflammation, the contribution of gram-negative peptidoglycan to disease has not been characterized . The ability of cell wall, purified peptidoglycan, and soluble peptidoglycan subcomponents from Haemophilus influenzae to provoke inflammation was determined in a rabbit model of meningitis . Haemophilus peptidoglycan, with or without associated proteins, produced brain edema at > or = 0.1 micrograms/mL of cerebrospinal fluid (CSF); leukocytosis and protein accumulation in CSF occurred only at > or = 10.0 micrograms/mL of CSF . Solubilized peptidoglycan was 10-fold more active than intact cell wall . The bioactivity of peptidoglycan from ampicillin-resistant H . influenzae was at least twofold greater than that of ampicillin-sensitive strains . Consistent with these pathologic effects of purified peptidoglycan, ampicillin-induced bacterial lysates in which endotoxin was neutralized induced brain edema and protein influx but little leukocytosis . Thus, peptidoglycan seems to contribute to the pathology of gram-negative meningitis, particularly brain edema.

J Infect Dis, 1993 Feb, 167(2), 365 - 71
Anti-capsular polysaccharide antibodies reduce nasopharyngeal colonization by Haemophilus influenzae type b in infant rats; Kauppi M et al.; Haemophilus influenzae type b (Hib) conjugate vaccines reduced oropharyngeal carriage of Hib among children in Finland and the United States . To study the mechanisms of this reduction, a colonization model in infant rats with passively administered antibodies was developed . Of the pups, 94% were colonized 48 h and 64% 7 days after intranasal inoculation with approximately 2500 cfu of Hib . Intranasally administered anti-Hib antibodies, including human IgG and both serum and secretory IgA (sIgA) as well as murine monoclonal anti-Hib capsular polysaccharide (PS) of IgG1 isotype, given simultaneously with, before, or after bacteria, significantly reduced nasopharyngeal colonization by Hib . Hib colonization was also significantly reduced when the antibodies were given intraperitoneally, with a resultant anti-Hib PS serum concentration of > or = 7 micrograms/mL . Thus, anti-Hib PS antibodies, both sIgA and IgG, can function on the mucosal surface and prevent colonization.

J Infect Dis, 1993 Feb, 167(2), 356 - 64
Genes involved in Haemophilus influenzae type b capsule expression are frequently amplified; Corn PG et al.; The genes involved in Haemophilus influenzae type b capsule expression are present as a duplication of an approximately 18-kb DNA segment (the Cap b locus) . It has been shown previously that recombination occurs between the two copies of the repeat, resulting in deletion of one copy and loss of capsule expression at frequencies of 0.1%-0.5% . The present study tested the hypothesis that the duplicated arrangement could serve as a template for further amplification of capsule gene sequences . Southern hybridization analysis of 66 type b invasive isolates showed that amplifications exist and are moderately common (23/66 were amplified) . In addition to three copies of the 18-kb repeat, four copies were detected in some strains, and up to five copies in 1 isolate . By ELISA, a five-copy strain made about six times more capsular polysaccharide than did an isogenic two-copy derivative . The evolutionary significance of the duplicated arrangement may be its ability to rapidly amplify under conditions where it is advantageous to produce more capsule.

Eur J Clin Microbiol Infect Dis, 1993 Feb, 12(2), 134 - 41
In vitro activity of E-4868, a new trifluoroquinolone, compared to six similar compounds; Barrett MS et al.; The compound E-4868 (Laboratorios Dr . Esteve) is a trifluoro, 7-azetidinyl quinolone with properties resembling those of other fluoroquinolones . Its activity in vitro was compared to that of six other similar drugs against more than 700 nosocomial isolates using standard methods . The MIC50s of E-4868 for enteric bacilli ranged from 0.015 to 0.25 micrograms/ml, being highest for Providencia spp . Pseudomonas aeruginosa strains were two-fold more susceptible to E-4868 than to ofloxacin . MICs of E-4868 for Haemophilus influenzae, Moraxella catarrhalis and pathogenic Neisseria spp . were all < or = 0.12 micrograms/ml . E-4868 was equal in activity to or eight-fold more active than ciprofloxacin against gram-positive cocci . The MICs of E-4868 for pneumococci were all < or = 0.5 micrograms/ml but anaerobes such as Bacteroides fragilis were generally less susceptible (MIC90, 4 micrograms/ml) . There was almost complete cross-resistance to several other fluoroquinolones . Resistant mutants were selected by a multiple passage technique but the rate of mutation to resistance was very low (< 10(-8)) at an 8 x MIC.

Curr Opin Pediatr, 1993 Feb, 5(1), 55 - 9
Haemophilus influenzae type b polysaccharide-protein conjugate vaccines in children; Eskola J et al.; Prevention of invasive infections caused by Haemophilus influenzae type b (Hib) bacteria has become possible with new vaccines . Covalent coupling to a protein carrier increases the immunogenicity of Hib capsular polysaccharide, and changes it to a T-cell dependent antigen . In clinical use, the conjugate vaccines are immunogenic in infancy, induce immunologic memory, and protect efficiently from invasive infections . They even seem to reduce oropharyngeal carriage of Hib bacteria . Wide-scale use of Hib conjugate vaccines has demonstrated their safety and low reactogenicity . Studies to combine them with other childhood vaccines are in progress . First signs of reduction of severe Hib infections can already be seen in countries where Hib conjugate vaccines are in wide use.

Curr Opin Pediatr, 1993 Feb, 5(1), 35 - 40
Infections in day care; Ferson MJ; The number of preschool-aged children who attend day care has increased dramatically in recent years . Factors promoting spread of infections in this setting include crowding, lack of hygiene, high prevalence of early exploratory behaviors, and the likelihood of many susceptible children being in close contact . As a result, children attending day care experience a great number of episodes of respiratory and gastrointestinal illness than do other children . Moreover, the risk of a number of specific infections, including Haemophilus influenzae type b and hepatitis A, is increased by attendance in day care . Day-care staff are at increased risk of a number of infections, some of which, including cytomegalovirus and parvovirus B19, may have adverse consequences to a fetus . The presence of children in day care increases the risk of illness among staff and family members and may promote the circulation of infections in the community as a whole.

Pediatr Allergy Immunol, 1993 Feb, 4(1), 1 - 5
Low IgG4 concentrations in infants with Haemophilus influenzae type b infections; Beard LJ et al.; Haemophilus influenzae type b causes considerable morbidity and mortality in infants and young children . Immunity to this organism has been attributed in part to the formation, and increase with age, of antibodies to the capsular polysaccharide of the bacteria . A degree of immunodeficiency could explain why some infants and young children develop invasive haemophilus disease . In this study we investigated immunocompetence in ten infants with invasive haemophilus disease . We found normal lymphocyte mitogen responses, neutrophil iodination and bactericidal and fungicidal capacities in this group . While we found no deficiencies of any of the immunoglobulin classes, three patients had low concentrations of IgG4 and two of them had low concentrations of IgG2 as well . These findings suggest that in some infants who develop haemophilus infections, the measurement of IgG subclasses may reveal immune defects that would not otherwise be apparent.

Arch Fr Pediatr, 1993 Feb, 50(2), 139 - 41
{C2 deficiency discovered in pneumococcal meningitis}; Monfort-Gouraud M et al.; BACKGROUND . Congenital deficiencies of complement system proteins are rare . Patients with C2 deficiency have a high incidence of vascularitis syndromes . Most patients with this deficiency have no problems with increased susceptibility to infection, most commonly due to pneumococci, presumably because of the protective function of the alternative pathway . CASE REPORT . A 22 month-old girl was admitted because of acute meningitis and otitis . She had had 2 episodes of otitis media at the age of 1 year . Analysis of the CSF showed that this meningitis was due to pneumococcal infection . Recovery was complete after 15 days of antibiotic therapy . Total hemolytic complement activity (CH50) was low during the infection; one month later, the CH50 value was about zero as was C2, while C3 and C4 were normal . The patient was given polyvalent pneumococcal and anti-Haemophilus vaccines plus prophylactic penicillin G . Laboratory tests for systemic lupus erythematosus were negative . CONCLUSION . A defect of complement function should be suspected in any patient with severe of recurring pyogenic infections . Complement disorders can be detected one month later by means of the relatively simple hemolytic complement assay.

Rev Med Chil, 1993 Feb, 121(2), 199 - 200
{Purulent meningitis: a long-standing problem}; Borgono JM; Bacterial meningitis is a problem for Public Health that has to be reviewed periodically . Most of the infections are due to Meningococcus, Haemophilus influenzae or Streptococcus pneumoniae . Seventy per cent of the cases are seen in children less than 5 years old; mortality ranges between 5% to 20% of the patients . Progress has been made with vaccination for Meningococcus types A and C and for H influenzae type B . In Chile, meningococcal meningitis is endemic, with epidemic bouts in the north part of the country . Currently, studies are in progress in Santiago with vaccination against H influenzae type B, in the hope that it can be extended to the rest of the country.

Infect Agents Dis, 1993 Feb, 2(1), 1 - 16
Nontypeable Haemophilus influenzae disease: epidemiology, pathogenesis, and prospects for prevention; St Geme JW 3rd; Nontypeable Haemophilus influenzae has emerged as an important human pathogen and is associated with a wide range of diseases . As methods for subtyping isolates have improved, our understanding of the epidemiology and pathogenesis of nontypeable H . influenzae disease has grown . These advances have facilitated identification of a number of bacterial factors with potential as vaccine components . In this review we discuss methods of classifying nontypeable H . influenzae, the epidemiology of disease due to these organisms, bacterial and host factors contributing to disease pathogenesis, and the status of efforts to develop an effective vaccine.

Infect Immun, 1993 Feb, 61(2), 650 - 5
Role of lipooligosaccharide in virulence of the Brazilian purpuric fever clone of Haemophilus influenzae biogroup aegyptius for infant rats; Rubin LG et al.; Clonally related strains of Haemophilus influenzae biogroup aegyptius have recently been associated with Brazilian purpuric fever (BPF), a fulminant, systemic disease in children . Using an infant rat bacteremia model for BPF, we found that a rat blood-passaged BPF isolate of H . influenzae biogroup aegyptius was more virulent than the original strain was . When compared with the original strain, the animal-passaged variant was found to display an altered lipooligosaccharide (LOS) phenotype and to lack pili . To examine the role of LOS phenotype and pili in virulence, we isolated isogenic variants differing in LOS phenotype or expression of pili . The virulence of variants was compared by examining the results of blood cultures obtained 24 h after intraperitoneal inoculation with 10(5) CFU . Our results indicate that the LOS phenotype is a critical determinant of BPF clone virulence for infant rats . To a lesser extent, the absence of piliation and an undefined additional factor(s) contribute to virulence.

Infect Immun, 1993 Feb, 61(2), 432 - 8
Non-epitope-specific suppression of the antibody response to Haemophilus influenzae type b conjugate vaccines by preimmunization with vaccine components; Barington T et al.; Recently, conjugate vaccines containing Haemophilus influenzae type b capsular polysaccharide (HibCP) coupled to protein carriers were introduced for use in infants and certain adult risk groups . Similar conjugate vaccines against other capsulated bacteria are currently under development for both children and adults . Despite its potential importance, the possible influence of preexisting immunity to the components of such conjugates on the vaccination response in humans has been addressed by few studies . To study this issue, we randomized 82 healthy adult volunteers into six groups and vaccinated them twice, with a 4-week interval between immunizations . Four groups received tetanus toxoid (TT) or diphtheria toxoid (DT) and then HibCP coupled to TT (HibCP-TT) or DT (HibCP-DT) . Two groups received HibCP-TT followed by HibCP-DT or vice versa . The total antibody levels to HibCP, TT, and DT and the anti-HibCP immunoglobulin G1 (IgG1) and IgG2 levels were measured before and 4 weeks after the immunizations . For some of the vaccinees, the number of circulating antibody-secreting cells was evaluated 7 days after immunization . Surprisingly, preimmunization with the relevant carrier protein reduced the subsequent increase in the total HibCP antibody levels (P < 0.05), affecting the IgG1 and the IgG2 subclasses equally . Also, the responses to the carrier portions of the conjugates were suppressed, as demonstrated by the lack of significant increases in the antibody levels (P > or = 0.29) and, for HibCP-TT, by reduced numbers of anticarrier antibody-secreting cells (P = 0.009) . Similar non-epitope-specific suppression was seen in the groups receiving both conjugates . Thus, preimmunization with one conjugate reduced the subsequent response to the carrier portion of the other conjugate (HibCP-DT and then HibCP-TT, P = 0.00002; HibCP-TT and then HibCP-DT, P = 0.06) as well as to HibCP itself . Possible mechanisms behind this non-epitope-specific suppression and its relevance for vaccine development are discussed.

Tidsskr Nor Laegeforen, 1993 Jan 30, 113(3), 329 - 33
{Haemophilus influenzae infections in children}; Wium ET et al.; Haemophilus influenzae may cause serious infections, especially in small children . During the period 1980-90, 45 children with systemic H influenzae infections were admitted to the University Clinic, Tromso . 17 patients had epiglottitis in the same period, but are not included in this material . One of the four septicemia patients and two of the 35 children with meningitis died, giving an overall lethality of 4.8% . Five of the patients with meningitis experienced neurological sequelae (14% of the patients with meningitis) . Two of the systemic isolates of H influenzae were resistant to ampicillin because of beta-lactamase production, but all the isolates were susceptible to chloramphenicol and 3rd generation cephalosporins.

Med Klin (Munich), 1993 Jan 15, 88(1), 16 - 20
{Sulbactam/ampicillin in comparison with cefuroxime for infections of the lower respiratory tract . Results of a prospective, randomized comparative study}; Schwigon CD et al.; In a randomized prospective study, ampicillin (AMP) in combination with the beta-lactamase-inhibitor, sulbactam (SBT) was compared with cefuroxime (CXM) in 73 hospitalized patients with lower respiratory tract infections . 36 patients received SBT/AMP 1 g/2 g t.i.d . and 37 patients received CXM 1.5 g t.i.d.--both in the form of i.v . infusion . The duration of treatment ranged from five to twelve days, with a median of eight days in each group . 23 patients (64%) of the SBT/AMP group had pneumonia, while 13 (36%) had acute purulent bronchitis; 13 of the patients (36%) received artificial respiration . 23 patients (62%) of the CXM group had pneumonia and 14 (38%) acute purulent bronchitis; eight patients (22%) required artificial respiration . In 54 patients (SBT/AMP: 26; CXM: 28) initial culture yielded bacterial pathogens, mainly Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, Staphylococcus aureus and pneumococci . 35 patients in each group were clinically evaluable . 31 patients (89%) responded to treatment with SBT/AMP, and 28 patients (80%) to treatment with CXM . Four patients (11%) who received SBT/AMP failed to respond, as did seven patients on CXM . The bacteriological efficacy was assessed in 26 patients of the SBT/AMP group: in 22 cases (84%) baseline pathogens were eradicated, while in two patients (8%) each, there was persistent infection and a superinfection, respectively . In 23 patients (82%) of the CXM group (28 patients evaluated) the pathogens were eradicated, while three cases (11%) had persistent infection, and two (7%) superinfection . Apart from a case of exanthema under CXM, no adverse drug reactions were reported . No statistically significant differences were to be seen between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

J Am Vet Med Assoc, 1993 Jan 15, 202(2), 273 - 7
Prophylactic efficacy of tilmicosin for bovine respiratory tract disease; Morck DW et al.; The prophylactic administration of injectable tilmicosin for pneumonia in weaned beef calves was investigated in 1,806 animals . Comparisons were made among calves receiving an "on-arrival" injection of tilmicosin, calves receiving a single injection of long-acting oxytetracycline, and calves receiving no prophylaxis . Morbidity and mortality attributable to pneumonia, morbidity and mortality attributable to all causes, and case fatality were significantly lower in the group of calves that received tilmicosin, compared with calves that received long-acting oxytetracycline and calves that received no prophylactic antibiotic . Mean time to initial pneumonia treatment was significantly extended in calves that received prophylaxis, compared with those that received no antibiotic on arrival at the feedlot . Calves that received tilmicosin gained significantly more weight than calves that received oxytetracycline . Calves that were not treated for pneumonia during the trial period gained significantly more weight than did those calves that were treated for pneumonia regardless of experimental group . The majority of mortalities were attributable to fibrinous pneumonia (31/34) . Important bacterial isolates (Pasteurella spp, Haemophilus somnus, Actinomyces pyogenes) obtained at necropsy did not have resistance to tilmicosin in association with administration of tilmicosin as prophylaxis for pneumonia . However, bacterial resistance to trimethoprim/sulfonamide and to oxytetracycline were commonly found in these postmortem isolates.

JAMA, 1993 Jan 13, 269(2), 246 - 8
Declining incidence of Haemophilus influenzae type b disease since introduction of vaccination; Murphy TV et al.; OBJECTIVE--To determine the incidence of invasive Haemophilus influenzae type b disease in children living in Minnesota and Dallas County, Texas, before and since introduction of plain polysaccharide vaccine in 1985, and conjugate vaccine in 1988 . Initially, use of these vaccines was limited to infants 18 months of age and older . DESIGN--Identification of culture-proven cases of H influenzae type b disease was through systems of active, laboratory-based surveillance . The mean incidence of disease (cases observed/100,000 child-years) for 1983 and 1984 served as a baseline for comparison with subsequent years through 1991 . PARTICIPANTS--Children less than 5 years of age in Minnesota and Dallas County, Texas . Overall, there were 2557 confirmed age-eligible cases of invasive H influenzae type b disease from 1983 through 1991 . RESULTS--Between the 1983-1984 baseline and 1991, the incidence of H influenzae type b disease decreased 85% in Minnesota and 92% in Dallas . Notably, declines in incidence were observed in children in the age group being vaccinated as well as in infants younger than 18 months of age prior to introduction of vaccination . CONCLUSION--In two widely separated areas of the United States, a profound decrease in the incidence of H influenzae type b disease has occurred . The data suggest that vaccination may be protecting against disease, as well as decreasing the spread of infection to unvaccinated infants.

JAMA, 1993 Jan 13, 269(2), 227 - 31
Decreases in invasive Haemophilus influenzae diseases in US Army children, 1984 through 1991; Broadhurst LE et al.; OBJECTIVE--To document trends in the incidence of invasive Haemophilus influenzae diseases in young children of US Army active duty soldiers following the publication of H influenzae type b immunization recommendations for young children between 1985 and 1990 . DESIGN--A population-based surveillance of hospital discharge diagnoses for H influenzae invasive diseases . SETTING--Military and civilian medical treatment facilities around the world . PATIENTS--There was a mean population of nearly 200,000 US Army health care beneficiaries younger than 5 years of age each year of the study . OUTCOME MEASURES--Annual total and age-specific incidences of the six most common H influenzae invasive diseases in this population (meningitis, epiglottitis, septicemia, pneumonia, cellulitis, and septic arthritis) . RESULTS--The annual number of cases of H influenzae invasive diseases decreased from a high of 188 in 1986 to 43 in 1991 . The incidence in the age group at highest risk for H influenzae disease, those 6 to 11 months of age, decreased from 355 per 100,000 children in 1986 to 116 per 100,000 in 1991 (P < .0001, chi 2 for trend) . The incidence for H influenzae meningitis declined from 59 per 100,000 children in 1986 to 6 per 100,000 in 1991 (P < .0001, chi 2 for trend) . CONCLUSIONS--The decrease in H influenzae invasive diseases closely follows the dates of H influenzae type b vaccine licensure for use in progressively younger age groups . Some age groups, however, experienced a decline in disease rates even before becoming eligible for vaccination.

JAMA, 1993 Jan 13, 269(2), 221 - 6
Decline of childhood Haemophilus influenzae type b (Hib) disease in the Hib vaccine era; Adams WG et al.; OBJECTIVE--Effective Haemophilus influenzae type b (Hib) conjugate vaccines were first licensed for use in US children at least 18 months old in December 1987 and for infants at least 2 months old in October 1990 . We evaluated trends in Hib disease associated with licensure of Hib conjugate vaccines . DESIGN--Data from two sources, an intensive laboratory-based active surveillance system and the National Bacterial Meningitis Reporting System (NBMRS), were used separately to evaluate disease incidence . Data from vaccine manufacturers on Hib vaccine doses distributed in the United States were compared with trends in Hib disease incidence . RESULTS--The age-specific incidence of Hib disease among children less than 5 years old decreased by 71% from 37 per 100,000 persons in 1989 to 11 per 100,000 persons in 1991 (active surveillance data) . Haemophilus influenzae meningitis incidence decreased by 82% between 1985 and 1991 (NBMRS data) . Increases in doses of Hib vaccine distributed in the United States coincided with steep declines in Hib disease . Both surveillance systems showed decreased rates of Hib disease in infants less than 1 year old before vaccine was licensed for use in this age group . Haemophilus influenzae type b disease incidence in persons at least 12 years old and pneumococcal meningitis incidence in children less than 5 years old did not change substantially during the same period; therefore, decreased Hib disease in children less than 5 years old is not likely to be explained solely by changes in surveillance sensitivity or decreases in bacterial disease due to changes in medical practice . CONCLUSION--Our data suggest that conjugate vaccines have already had a marked impact on the incidence of Hib disease in the United States, preventing an estimated 10,000 to 16,000 cases of Hib disease in 1991 . The decline of disease in infants less than 1 year old before licensure for this age group warrants further investigation.

N Engl J Med, 1993 Jan 7, 328(1), 21 - 8
Acute bacterial meningitis in adults . A review of 493 episodes; Durand ML et al.; BACKGROUND AND METHODS . To characterize acute bacterial meningitis in adults, we reviewed the charts of all persons 16 years of age or older in whom acute bacterial meningitis was diagnosed at Massachusetts General Hospital from 1962 through 1988 . We included patients who were admitted after initial treatment at other hospitals . RESULTS . During the 27-year period, 445 adults were treated for 493 episodes of acute bacterial meningitis, of which 197 (40 percent) were nosocomial . Gram-negative bacilli (other than Haemophilus influenzae) caused 33 percent of the nosocomial episodes but only 3 percent of the community-acquired episodes . In the 296 episodes of community-acquired meningitis, the most common pathogens were Streptococcus pneumoniae (37 percent), Neisseria meningitidis (13 percent), and Listeria monocytogenes (10 percent); these organisms accounted for only 8 percent of the nosocomial episodes . Only 19 of the 493 episodes of meningitis (4 percent) were due to H . influenzae . Nine percent of all patients had recurrent meningitis; many had a cerebrospinal fluid leak . Seizures occurred in 23 percent of patients with community-acquired meningitis, and 28 percent had focal central nervous system findings . Risk factors for death among those with single episodes of community-acquired meningitis included older age (> or = 60 years), obtunded mental state on admission, and seizures within the first 24 hours . Among those with single episodes, the in-hospital mortality rate was 25 percent for community-acquired and 35 percent for nosocomial meningitis . The overall case fatality rate was 25 percent and did not vary significantly over the 27 years . CONCLUSIONS . In our large urban hospital, a major proportion of cases of acute bacterial meningitis in adults were nosocomial . Recurrent episodes of meningitis were frequent . The overall mortality rate remained high.

Antonie Van Leeuwenhoek, 1993 Jan, 63(1), 35 - 8
The use of neural networks to aid in microorganism identification: a case study of Haemophilus species identification; Kennedy MJ et al.; Neural networks were evaluated as a tool for identifying microorganisms . Data from a microorganism identification table were used to train a neural network . Based on the results of identification tests the neural network could correctly identify each Haemophilus species from a group of 13 Haemophilus species.

Respiration, 1993, 60 Suppl 1, 32 - 7
Relevance of antibiotic tissue penetration in treating respiratory tract infections; Kneer J; The majority of bacterial respiratory tract infections are caused by streptococci, Haemophilus spp . and Moraxella catarrhalis . These pathogens are located extracellularly . In logical consequence, the bactericidal action of the antimicrobial is required in these loci . To define the reasonable dosing regimen for effective eradication without creating unnecessary toxic potential we need to know (1) the distribution principles and kinetics, and (2) the correct correlation between concentration profiles in extracellular fluid (ECF) and blood . According to the permeability of the vascular capillaries unbound drug concentrations in plasma and ECF are in a dynamic equilibrium . Thus, for the beta-lactam antibiotics therapeutic efficacy is predictable by maintaining the free drug concentration above the bacterial minimum inhibitory concentration . Tissue homogenate data can only be useful if correctly interpreted by correcting for the partitioning between the tissue components.

Eur Arch Otorhinolaryngol, 1993, 250 Suppl 1, S3 - 6
The microbiology of acute and chronic sinusitis and otitis media:a review; van Cauwenberge PB et al.; There exists no real controversy about the role of aerobic bacteria in acute sinusitis and in acute otitis media . The "infernal trio" Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are by far the most common pathogens in these acute infections . On the contrary, there is still much debate about the normal flora of the paranasal sinuses and the middle ear, although there are some reports of the presence of anaerobes and aerobes in the majority of the normal paranasal sinuses . In chronic sinusitis bacteriological cultures show a greater variation than those in acute sinusitis . Nonetheless, it is demonstrated in most studies that besides the "infernal trio" additional bacteria are present, including anaerobes and gram negative bacteria . In otitis media with effusion (OME) we find the same bacteria as in acute otitis media (AOM) and a pathologic flora in the nasopharynx seems to be important for both AOM and OME . In chronic otitis cultures are nearly always positive and reveal Pseudomonas species, Klebsiella pneumoniae, Staphylococcus aureus, Proteus species and anaerobes.

Eur Arch Otorhinolaryngol, 1993, 250 Suppl 1, S13 - 4
Effectiveness and safety of ofloxacin in chronic otitis media and chronic sinusitis in adult outpatients; Gehanno P et al.; A multicentric study was conducted to evaluate the clinical efficacy and tolerance of ofloxacin in the treatment of chronic sinusitis and chronic otitis (CSOM) in outpatients . Two hundred milligrams of ofloxacin was administered twice a day orally for 12 days in 198 patients with chronic sinusitis and 215 patients with CSOM . Cultures for bacteriology were carried out before treatment . The spectrum of pathogens sensitive to ofloxacin included Staphylococcus aureus, Pseudomonas aeruginosa, Proteus mirabilis and Haemophilus influenzae . Higher concentrations of ofloxacin were obtained at sites of infection than in serum . Favorable results were achieved clinically in 93.7% of chronic sinusitis cases and 93.9% of CSOM cases . Adverse effects occurred in only 4.1% of cases . These results support the use of ofloxacin as the drug of first choice in the treatment of chronic sinusitis and CSOM in adult outpatients.

Eur J Epidemiol, 1993 Jan, 9(1), 64 - 9
Antimicrobial resistance among clinical isolates of Haemophilus influenzae in northern Italy . Collaborative Study on Pediatric Infectious Diseases; Garlaschi ML et al.; Only scanty data are available on the susceptibility of Haemophilus influenzae in Italy . The in vitro activity of ampicillin, ampicillin-sulbactam, cefaclor, cefuroxime, cefotaxime, chloramphenicol, erythromycin and trimethoprim-sulfamethoxazole against 327 strains of Haemophilus influenzae (55 encapsulated, 272 non-typeable) isolated from adults and children in northern Italy, between January 1984 and December 1989, was compared . Patients were affected by meningitis or other invasive infections, conjunctivitis, otitis, sinusitis, pneumonia or bronchitis . Minimal inhibiting concentrations were determined by a microdilution technique in Mueller Hinton broth supplemented with 10 microliters/ml NAD and 2-5% lysed horse blood . A concentration of 1 x 10(5) to 5 x 10(5) CFU/ml was used as the inoculum . The antibiotics were tested at concentrations ranging from 0.03 to 64 microliters/ml with the exception of trimethoprim-sulfamethoxazole, for which the range of concentrations examined were 0.01/0.25 to 32/512 microliters/ml . All the strains tested were susceptible to ampicillin-sulbactam, cefuroxime and cefotaxime, and more than 95% were susceptible to ampicillin, cefaclor and chloramphenicol . Only 4% were susceptible to erythromycin but most minimal inhibiting concentrations fell into the intermediate category . Strains isolated from adults were more susceptible to trimethoprim-sulfamethoxazole than strains isolated from children (85% vs 66%; p = 0.011).

Enferm Infecc Microbiol Clin, 1993 Jan, 11(1), 19 - 28
{Resistance in Haemophilus influenzae in Spain . 2d study (1990)}; Perea EJ et al.; AIM: To study the resistance to strains of H . influenzae simultaneously isolated during 1990 in 10 Spanish cities with this being the second multicentric study carried out in Spain . METHODS: Three hundred eight strains of H . influenzae were consecutively isolated with less than 50% being from the respiratory tract . The sensitivity by microdilution in supplement Isosensitest was studied . RESULTS: Thirty-five percent of the strains were producers of beta-lactamase which predominate among those isolated in systemic infections and specially among those from Madrid (58.78%) and Barcelona (61.8%) . The strains producing beta-lactamase were more resistant to all the antimicrobials than the non producers . Five point two percent of the strains were resistant to ampicillin by non enzymatic mechanisms . Resistance to chloramphenicol is frequent (28.6%) especially among strains producing beta-lactamase, strains of ocular origin and ORL (46%) and systemic infections (74.3%) . The distribution is irregular, being more frequent in Seville (66.7%) and not detectable in Barcelona . Resistance to tetracycline is also usually linked to the production of beta-lactamase and not necessarily to that of chloramphenicol . Resistance to cotrimoxazole is the most frequent (67.5%) specially in Valladolid (87.5%) . Resistance to cefaclor is of 60.7% being the most frequent among those isolated from ocular processes and ORL . Only 28 strains (9.1%) were sensitive to all the antimicrobials tested . Thirty-nine percent were multiresistant . CONCLUSIONS: The authors found a slight increase in the high resistance detected in 1986 . This increase was not uniform in all of Spain being significant in Madrid with producers of beta-lactamase, in Seville to chloramphenicol, to tetracycline in Bilbao and cotrimoxazole in Valencia.

Nippon Jibiinkoka Gakkai Kaiho, 1993 Jan, 96(1), 29 - 34
{Association of Chlamydia pneumoniae infection with otitis media with effusion}; Ogawa H et al.; Chlamydia pneumoniae has recently been recognized to cause various human respiratory tract diseases, including pharyngitis, bronchitis and pneumonia . The most common pathogens of respiratory tract infections such as Streptococcus pneumoniae and Haemophilus influenzae are frequently present in middle ear effusions . Therefore, it is possible that C . pneumoniae play a role in otitis media with effusion (OME) . Isolation of C . pneumoniae from middle ear aspirates of OME was performed by the culture method using the HeLa 229 or HL cell line . Identification as C . pneumoniae was based on positive staining for inclusions by a species-specific fluorescein-conjugated monoclonal antibody . C . pneumoniae was recovered from 17.8% (13 of 73) of the patients with acute OME, and 7.1% (3 of 42) of those with chronic OME, Moreover, antibodies to C . pneumoniae were measured by the microimmunofluorescence method in 14 patients who yielded the agent, and all of them had detectable antibodies to C . pneumoniae . Evidence of recent or current infection by the organism was found in nine patients on the basis of either on IgM antibody titer of 1:16 or higher, or a four-fold rise in the titer of IgG antibody . The study findings indicate that C . pneumoniae can cause OME and that the organism is a new candidate as an etiological agent of middle ear diseases.

Clin Ther, 1993 Jan-Feb, 15(1), 88 - 96
Global surveillance of bacterial susceptibility to cefaclor: 1988-1990; Preston DA; In vitro data on bacterial susceptibility to cefaclor were collected from clinical trials conducted in 15 European countries, South Africa, Canada, and the United States . Among the respiratory pathogens, 94% of Haemophilus influenzae, 98.6% of Streptococcus pneumoniae, 98.8% of Streptococcus pyogenes, and 98.1% of Moraxella catarrhalis were susceptible to cefaclor . Over 90% of the tested isolates of the most common urinary tract pathogen, Escherichia coli, were susceptible to cefaclor . Virtually all of the pathogens that may infect skin and soft tissues, S pyogenes and Staphylococcus aureus (methicillin-susceptible strains), were cefaclor susceptible . These data confirm that the major pathogens in bacterial infections of the upper and lower respiratory tract, of the skin and related structures, and of the urinary tract remain susceptible to cefaclor after more than 13 years of widespread clinical use.

Jpn J Antibiot, 1993 Jan, 46(1), 36 - 43
{Cefuzonam penetration into cerebrospinal fluid}; Yasumoto Y et al.; We studied the penetration of cefuzonam (CZON) into the cerebrospinal fluid (CSF) in 20 patients with neurosurgical diseases . Influences of the presence of meningeal reaction and the intensity of brain damage on CSF penetration of CZON were also examined . Concentrations of CZON in serum and CSF were determined using the thin-layer cup method before and 1, 2, 4, and 6 hours after 2 g of CZON was administered intravenously . The serum concentration at 1 hour was 60.4 +/- 31.3 (mean +/- S.D.) microgram/ml, then rapidly decreased to 2.1 +/- 2.3 micrograms/ml at 6 hours . In contrast, the CSF concentration gradually increased, reached a peak level of 0.319 +/- 0.313 micrograms/ml at 4 hours and then slowly decreased to 0.273 +/- 0.249 micrograms/ml at 6 hours . The CSF penetration ration: CZON ({CSF}/{serum}) was 5.6% at 4 hours . The peak CSF concentration in patients with meningeal reaction (0.465 +/- 0.364 micrograms/ml at 2 hours) was about 2-fold higher than that in those without the reaction (0.249 +/- 0.223 micrograms/ml at 4 hours) . The peak CSF concentrations in patients with slight, moderate, and severe brain damage were 0.231 +/- 0.133 micrograms/ml at 4 hours, 0.270 +/- 0.232 micrograms/ml at 4 hours, and 0.680 +/- 0.467 micrograms/ml at 2 hours, respectively . CSF penetration of CZON was augmented in patients with meningeal reaction or severe brain damage . These findings indicate that the concentration of CZON in CSF after intravenous administration is sufficient for treatment of meningitis or infections after neurosurgical operations caused by such bacteria as Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, and Streptococcus pneumoniae.

Infection, 1993 Jan-Feb, 21(1), 66 - 70
Penetration of ofloxacin into nasal tissues; Tolsdorff P; The average concentration in 75 female/male patients was 1.90 +/- 1.10/1.55 +/- 0.62 mg/l in serum, 0.81 +/- 0.42/0.74 +/- 0.48 mg/kg in bone, 2.40 +/- 1.16/1.94 +/- 0.87 mg/kg in cartilage, and 2.35 +/- 1.28/1.99 +/- 1.02 mg/kg in mucosa . In each case the highest serum or tissue concentrations were observed 2 hours after the last ofloxacin administration (serum 2.60 +/- 0.41 mg/l, bone 1.10 +/- 0.75 mg/kg, cartilage 3.40 +/- 0.86 mg/kg, mucosa 3.50 +/- 1.05 mg/kg), but even 8 hours after the last dose the levels still exceeded the MIC 90% of e.g . Pseudomonas aeruginosa, Staphylococcus aureus or Haemophilus influenzae . The clinical investigations carried out show that ofloxacin represents a new oral therapeutic agent of significant value in otorhinolaryngology, particularly in the treatment of problematic infections . As the investigations show, the level in healthy tissue is definitely within the therapeutic region for a period of 8 hours . In ENT (nasal and paranasal) infections, ofloxacin should be given for defined indications, e.g . for oral therapy of problematic infections due to P . aeruginosa, and if possible after identification of the pathogen.

Infection, 1993 Jan-Feb, 21(1), 63 - 5
Tissue and serum concentrations of ofloxacin in the ear region following a single daily oral dose of 400 mg; Tolsdorff P; Even after a single daily dose of 400 mg, the concentrations of ofloxacin in infected middle ear tissues are within the therapeutic range . Even 20 h after a single dose of 400 mg ofloxacin, the tissue concentrations in cartilage and cholesteatomatous matrix are in excess of the minimal inhibitory concentration for a number of pathogens, such as Staphylococcus aureus and Haemophilus influenzae . The especially high concentrations in middle ear mucosa, auricular cartilage and cholesteatomatous matrix are striking . No complications or side effects were observed during ofloxacin treatment in this study . The study demonstrates that a dose of 400 mg ofloxacin per day is an effective and patient orientated therapeutic regime for the treatment of ENT infections, particularly of ear infections.

Vaccine, 1993, 11 Suppl 1, S58 - 62
Anti-PRP antibody levels after a primary series of PRP-OMPC and persistence of antibody titres following primary and booster doses; Calandra GB et al.; The Haemophilus influenzae capsular polysaccharide-outer membrane protein conjugate, PRP-OMPC (PedvaxHIB) elicits very good antibody responses in infants > or = 2 months of age after the first dose . Increasing age at time of first vaccination correlates with higher antibody responses . Anti-PRP responses are consistently high with the first injection among all population groups studied . Booster doses stimulate anamnestic antibody responses after one year of age . Among US children (excluding Navajo and Apache children) given a primary injection at 14-18 months of age, the geometric mean titre (GMT) after 2 to 3 years was > 1 micrograms/ml . US children (excluding Navajo and Apache children) given a primary series at 2 and 4 months of age and a booster at 18 months of age also had an anti-PRP GMT > 1 micrograms/ml 2.5 years later . Navajo and Apache children given a primary series at 2 and 4 months of age and a booster at 12-15 months had antibody levels of 1.50 micrograms/ml one year later . Antibody persistence data suggest there will be long-term protection against Haemophilus influenzae b disease following immunization with PRP-OMPC.

Vaccine, 1993, 11 Suppl 1, S52 - 7
Prevention of Haemophilus influenzae type b disease; Santosham M; Haemophilus influenzae type b (Hib) is the leading cause of meningitis in children < 5 years of age . The majority of cases of Hib occur in infants < 2 years of age . Until recently the only vaccine available against this disease contained the pure polysaccharide (PRP) of Hib (Hib-PRP vaccine) . The Hib-PRP vaccine was demonstrated to be efficacious in infants > 18 months of age but not below that age . This product was licensed for routine use in the USA for children aged 24 months or more . Recently a hyperimmune globulin termed bacterial polysaccharide immune globulin (BPIg) was prepared by immunizing adult donors with Hib-PRP, meningococcal and pneumococcal vaccines . BPIg has been demonstrated to prevent Hib infections when it is administered to infants at 4-month intervals . However, BPIg has not been licensed for routine use in the USA . A number of new Hib conjugate vaccines have also been developed in the last few years by convalently linking the Hib-PRP to different carrier proteins . Four different Hib conjugate vaccines have undergone clinical trials in the USA . Two of these vaccines, HbOC (Hib capsular oligosaccharide linked to CRM197) and Hib-OMPC (Hib capsular polysaccharide linked to Neisseria meningitidis outer membrane protein complex) have been demonstrated to protect infants aged 2 months or more from Hib disease . Both HbOC and Hib-OMPC are currently licensed for routine use in the USA . The widespread use of these vaccines should have a substantial impact in reducing morbidity and mortality from Hib disease.

Vaccine, 1993, 11 Suppl 1, S46 - 51
Effect of immunity to the carrier protein on antibody responses to Haemophilus influenzae type b conjugate vaccines; Granoff DM et al.; The anticapsular antibody responses to some Haemophilus influenzae type b (Hib) conjugate vaccines may be enhanced by prior or simultaneous administration of the carrier protein used in the conjugate . Currently, there are two Hib conjugate vaccines licensed in the USA for use in infants beginning at 2 months of age: Hib polysaccharide coupled to an outer membrane protein complex of Neisseria meningitidis (PRP-OMPC), and Hib oligosaccharides conjugated to CRM197, a non-toxic mutant diphtheria toxin (HbOC) . The PRP-OMPC conjugate vaccine is immunogenic in infant monkeys and infant humans in the absence of carrier priming or additional carrier vaccination . The mechanism responsible for this immunogenicity is unknown but may relate to the adjuvanticity of the OMPC carrier . In contrast, data from infant rhesus monkeys and infant humans suggest that there may be a need for vaccination with diphtheria toxoid in order to maximize anti-PRP antibody responses to the HbOC conjugate . In addition, immunization with HbOC alone appears to be insufficient to elicit an antibody response to diphtheria toxoid . Thus, the need for additional vaccination with diphtheria toxoid in order to generate consistent anti-PRP antibody responses to HbOC may be a result of failure of the CRM197 protein carrier to elicit T-cell help . In infants in whom diphtheria-tetanus-pertussis (DTP) vaccination is deferred because of medical contraindications, vaccination with the PRP-OMPC conjugate would appear to be preferable to HbOC because of the ability of the former to elicit antibody responses in the absence of diphtheria toxoid vaccination.

Vaccine, 1993, 11 Suppl 1, S43 - 5
Epidemiology of invasive Haemophilus influenzae type b (Hib) disease in Israel; Dagan R; The results are reported of a nationwide prospective epidemiological study in Israel whose purpose was to provide a background for decisions regarding the need for Hib conjugate vaccinations . During the two study years, 344 patients < 13 years of age with a positive blood or cerebrospinal fluid culture for Hib were seen in 25 medical centres in which paediatric patients were hospitalized . The overall incidence of Hib disease was 34 per 100,000 persons < 5 years old, an incidence in the range of those reported for western Europe . Similarly, the incidence of meningitis was 18/100,000 . During the first year of life, the incidence of Hib was 117/100,000 and 93% of all cases were < or = 24 months old . The age distribution of our patients resembles that of immunologically compromised populations or of persons living in less industrialized areas, but the incidence of disease is similar to that found in western Europe . The data presented justify the widespread use of conjugate Hib vaccines in Israel.

Vaccine, 1993, 11 Suppl 1, S38 - 42
Epidemiology of Haemophilus influenzae type b disease in France; Reinert P et al.; Results are reported of an epidemiological study which spanned ten years and was carried out in two French departments . A total of 277 cases of Hib disease occurring in children < 5 years old are reported and, in this age group, the incidence is evaluated at 21/100,000 . Meningitis accounted for 64% of infections and epiglottitis for 7% . While the overall mortality rate was 3.3%, death was secondary to meningitis in 7/8 cases . Sequelae, which were all related to meningitis, were major in 1.2% of cases, severe in 9% of cases, and involved some hearing loss in 3.3% of cases . The monitoring networks set up in the two departments were characterized by sensitivities of 87 and 94%, respectively . They should prove useful in assessing the impact of vaccination, when large-scale implementation of vaccination has spread to both departments.

Vaccine, 1993, 11 Suppl 1, S34 - 7
Need for prevention of invasive Haemophilus influenzae type b infections in Geneva, Switzerland; Gervaix A et al.; Based on a retrospective study of invasive Haemophilus influenzae type b (Hib) diseases in Geneva from 1976 to 1989, we analysed the need for prevention of invasive Hib infections by vaccination in Geneva, Switzerland . The overall incidence rate among children younger than 5 years of age was 60.2/100,000 population but it was 121.5/100,000 and 92.1/100,000 in 1988 and 1989 respectively, indicating a statistically significant increase of invasive Hib infections during the study period . Of patients, 41.5% had meningitis, 36.6% epiglottitis and 21.9% had other forms of Hib infections . The occurrence was 2.1% in children under 3 months of age and 92.3% in children younger than 5 years of age . From 1984, > 21% of all new isolates were beta-lactamase-producing Hib strains . From 1976 to 1989, two children (1.1%) died from epiglottitis and 12 children with meningitis (15.8%) developed serious neurological deficits . These data emphasize the need for prevention of invasive Hib infections by vaccination in all infants in Geneva.

Vaccine, 1993, 11 Suppl 1, S30 - 3
Epidemiology of invasive Haemophilus influenzae type b disease in Scandinavia; Claesson BA; In all Scandinavian countries, most invasive Haemophilus influenzae type b (Hib) infections occur before the age of 5 years . The age-specific incidence of Hib meningitis in this age group is 26-35/100,000 per year in Denmark, Norway, Finland and Sweden and about 43/100,000 per year in Iceland . Of the meningitis patients, approximately 60% are younger than 2 years but Hib meningitis also occurs in older children and adults . The case fatality rate is low (1-3%) in children but the rate of neurological sequelae is considerable . The incidence of acute epiglottitis, the other main manifestation of Hib disease, varies considerably . In Sweden, four studies have shown a very high incidence in the age group 0-4 years, 21-34 cases/100,000 population per year compared to only 5-17 in the other Nordic countries . Epiglottitis is more common than Hib meningitis in older children and adults . In Scandinavia the age-specific incidence of all invasive Hib infections could be estimated to be about 50-65/100,000 per year in the most susceptible age group and the risk of contracting invasive Hib disease before the age of 15 years would be about 1/200-300 children.

Vaccine, 1993, 11 Suppl 1, S28 - 9
World-wide strategies for immunization against invasive Haemophilus influenzae type b disease; Iwarson S; Data available on the immunogenicity, safety and efficacy of Haemophilus influenzae type b (Hib) conjugate vaccines are encouraging and the prospects for controlling invasive Hib disease are good . The incidence of Hib meningitis in many industrialized countries increases sharply between 6 and 12 months of age and the first two doses of a Hib vaccine should ideally be given before that . In non-industrialized countries, the incidence peak is seen very early in life, which would require a very early start for Hib vaccination in such areas.

Vaccine, 1993, 11 Suppl 1, S21 - 7
Control of hepatitis B through routine immunization of infants: the need for flexible schedules and new combination vaccine formulations; West DJ et al.; Universal immunization of infants is essential to the control of hepatitis B in areas of high endemicity where infection commonly occurs in infants and children . It is also an attractive strategy for ultimately reducing hepatitis-B-associated acute and chronic liver disease in areas of lower endemicity where infections occur primarily in adolescents and adults . Integration of hepatitis B vaccine with other routine paediatric immunizations, using flexible scheduling, will enhance compliance while minimizing the need for additional resources . Clinical studies demonstrate that a very high proportion of healthy infants and adults develop a protective level of antibody when given hepatitis B vaccine using a wide range of schedules . Compliance with universal vaccination of infants against hepatitis B may be enhanced by the development of new combination vaccines (e.g . diphtheria-tetanus-pertussis-Haemophilus influenzae b-hepatitis B) that allow complete immunization against several antigens with a minimal number of injections.

Eur J Pediatr, 1993 Jan, 152(1), 24 - 30
Aetiology of community-acquired pneumonia in children treated in hospital; Korppi M et al.; Viral and bacterial antigen and antibody assays were prospectively applied to study the microbial aetiology of community-acquired pneumonia in 195 hospitalised children during a surveillance period of 12 months . A viral infection alone was indicated in 37 (19%), a bacterial infection alone in 30 (15%) and a mixed viral-bacterial infection in 32 (16%) patients . Thus, 46% of the 69 patients with viral infection and 52% of the 62 patients with bacterial infection had a mixed viral and bacterial aetiology . Respiratory syncytial virus (RSV) was identified in 52 patients and Streptococcus pneumoniae in 41 patients . The next common agents in order were non-classified Haemophilus influenzae (17 cases), adenoviruses (10 cases) and Chlamydia species (8 cases) . The diagnosis of an RSV infection was based on detecting viral antigen in nasopharyngeal secretions in 79% of the cases . Pneumococcal infections were in most cases identified by antibody assays; in 39% they were indicated by demonstrating pneumococcal antigen in acute phase serum . An alveolar infiltrate was present in 53 (27%) and an interstitial infiltrate in 108 (55%) of the 195 patients . The remaining 34 patients had probable pneumonia . C-reactive protein (CRP), erythrocyte sedimentation rate and total white blood cell count were elevated in 25%, 40% and 36% of the patients, respectively . CRP was more often elevated in patients with bacterial infection alone than in those with viral or mixed viral-bacterial infections . No other correlation was seen between the radiological or laboratory findings and serologically identified viral, bacterial or mixed viral-bacterial infections.(ABSTRACT TRUNCATED AT 250 WORDS)

Acta Otolaryngol, 1993 Jan, 113(1), 88 - 92
Micro-ecology of the nasopharyngeal bacterial flora in otitis-prone and non-otitis-prone children; Bernstein JM et al.; The quantitative bacteriology of the adenoid was studied in otitis-prone and non-otitis-prone children . alpha-hemolytic Streptococci (Viridans Streptococci) appeared to be predominant normal flora in the healthy nasopharynx . There was a decrease in alpha-hemolytic Streptococci in the otitis-prone child compared to the non-otitis-prone child . Concomitantly, there appears to be an increase in both nontypable Haemophilus influenzae (NTHI) and S . pneumoniae in the nasopharyngeal flora in the otitis-prone child . The mechanisms responsible for this alteration of the micro-ecology of bacteria of the nasopharynx may be related, in part, to factors that alter mucociliary function . These factors could be viral infection, allergy, local and systemic immunological deficiency and the indiscriminate use of antibiotics . An understanding of the relationship between the normal flora and the potential pathogens may be important in the understanding of both the pathogenesis of otitis media (OM) and possibly the treatment of this disease entity.

Wien Klin Wochenschr, 1993, 105(2), 59 - 60
{Incidence of Haemophilus influenza meningitis in Austria}; Vutuc C et al.; The incidence of Haemophilus influenza meningitis was analysed for the first time in Austria . In 1990 a total of 55 cases occurred, representing an incidence of 0.71/10(5) . Most of the patients were children aged less than 5 years (n = 42, 76.4%) . The incidence in the age group 0-4 years was 9.48/10(5), in each of the other 5-year age groups the incidence was lower than 1/10(5).

Pediatr Res, 1993 Jan, 33(1), 48 - 51
Haemophilus influenzae type B impairment of pial vessel autoregulation in rats; Berkowitz ID et al.; To examine the mechanisms of autoregulatory impairment in meningitis, we studied the effects of Haemophilus influenzae type b (Hib) on pial vessels during hemorrhagic hypotension in rats, using a cranial window technique . We prepared cranial windows in barbiturate-anesthetized, mechanically ventilated rats . Artificial cerebrospinal fluid or 10(5) Hib in cerebrospinal fluid (n = 7 each group) was suffused over the pial surface . Pial arteriolar diameter was measured hourly for 4 h . Autoregulation was assessed as the ability of pial arterioles to dilate in response to graded hemorrhagic hypotension at 2 and 4 h . Pial arterioles exposed to Hib dilated progressively to 149 +/- 27% of baseline at 4 h . Vessel diameter in the Hib group was significantly greater than in the control group beginning at 2 h . Autoregulation was progressively impaired in Hib-exposed rats compared with control rats {-5.85 +/- 1.38 versus -8.02 +/- 2.02 and -3.82 +/- 1.57 versus -8.53 +/- 1.72% dilation/kPa fall in mean arterial blood pressure at 2 and 4 h, respectively (p < 0.05)} . These data suggest that autoregulation is impaired in pial arterioles exposed to Hib because involved vessels have a finite dilatory capacity and are close to maximal dilation before hypotensive challenge.

Berl Munch Tierarztl Wochenschr, 1993 Jan, 106(1), 6 - 9
{The effectiveness of tilmicosin in respiratory diseases of swine}; Binder S et al.; Within the scope of the clinical evaluation of Tilmicosin in Enzootic Pneumonia of pigs, nasal swabs from 78 animals were taken, before and after oral medication of different doses (0, 100, 200, 300 mg Tilmicosin/kg dry food), and examined bacteriologically for Pasteurella multocida, Bordetella bronchiseptica und Haemophilus parasuis . The bacteria aforementioned were isolated from the nasal secretions of 83% of the pigs, 14 days after crowding without any prophylactic regime . It could be demonstrated, that pigs with clinical symptoms of Enzootic Pneumonia had a 50% higher prevalence-rate of multi-colonization with pneumotropic bacteria than healthy animals . Feeding 300 mg Tilmicosin/kg food for 9 and 14 days respectively, resulted in elimination of Pasteurella spp . and Haemophilus spp . The rate of newly Bordetella bronchiseptica infected pigs was lower than in the placebo-group . Parallel to these bacteriological results improvement of clinical signs and increased daily weight gain were observed.

Antimicrob Agents Chemother, 1993 Jan, 37(1), 14 - 8
Susceptibilities of beta-lactamase-producing and -nonproducing ampicillin-resistant strains of Haemophilus influenzae to ceftibuten, cefaclor, cefuroxime, cefixime, cefotaxime, and amoxicillin-clavulanic acid; Barry AL et al.; In in vitro studies we evaluated the susceptibilities of beta-lactamase-producing and -nonproducing, ampicillin-resistant strains of Haemophilus influenzae and compared them with those of ampicillin-susceptible strains . Ampicillin, amoxicillin-clavulanic acid, ceftibuten, cefaclor, cefuroxime, cefixime, and cefotaxime were evaluated by broth microdilution tests and disk diffusion tests . The disk diffusion tests accurately categorized beta-lactamase-producing strains and ampicillin-susceptible strains as being susceptible to the study drugs other than ampicillin . Ampicillin-resistant, beta-lactamase-nonproducing strains were relatively resistant to all seven study drugs, but the disk diffusion test did not always predict that resistance . The clinical relevance of the decreased susceptibility to various agents remains unclear, but to be conservative, all ampicillin-resistant, beta-lactamase-nonproducing strains might be assumed to be resistant to other beta-lactams . After excluding that small group of isolates, reliable susceptibility test results were obtained with lots of Haemophilus Test Medium that met quality assurance criteria.

Sex Transm Dis, 1993 Jan-Feb, 20(1), 5 - 9
Transport media for Haemophilus ducreyi; Dangor Y et al.; Stuart's, Amies' and four thioglycollate/hemin-based media containing, respectively, selenium dioxide and albumin (SA); selenium dioxide, L-glutamine and albumin (SGA); selenium dioxide and L-glutamine (SG); and L-glutamine and albumin (GA); were evaluated as transport media for Haemophilus ducreyi in a simulated, laboratory-based study . No transport medium was able to maintain the viability of H . ducreyi for more than 24 hours at room temperature . Amies' transport medium, however, maintained viability of H . ducreyi for up to 3 days and all the newly formulated transport media maintained viability of H . ducreyi for more than 4 days at 4 degrees C . Subsequently, swabs were taken from cases of genital ulcerations with a diagnosis of chancroid, plated directly onto selective media, and held at 4 degrees C in the two most efficient transport media (SGA and GA) for various periods of time . On direct plating, H . ducreyi was recovered from the genital ulcerations of 110 of 156 (71%) patients . The rates of recovery of H . ducreyi from transport media stored at 4 degrees C decreased with time . Although recovery was enhanced at day 4 (117/110 {106%}) using both SGA and GA, a recovery rate of 37/41 (90%) was obtained after storage in GA for 1 week.

Am J Trop Med Hyg, 1993 Jan, 48(1), 97 - 107
Meningitis and encephalitis at the Abbassia Fever Hospital, Cairo, Egypt, from 1966 to 1989; Girgis NI et al.; A total of 7,809 patients with meningitis or encephalitis were admitted to the Abbassia Fever Hospital in Cairo, Egypt from November 1, 1966 to April 30, 1989 . The etiology was Neisseria meningitidis (mostly group A) in 27.3% of the patients, Mycobacterium tuberculosis in 19.7%, Streptococcus pneumoniae in 7.3%, and Haemophilus influenzae in 4.1% . Almost 27% of the cases had purulent meningitis but without detectable etiology; however, the epidemiologic data suggest that most of these had meningococcal meningitis . Encephalitis was suspected in 12.5% of the patients . Most of the meningococcal, pneumococcal, and Haemophilus cases occurred during the winter months . The number of meningococcal and culture-negative purulent cases per year reached a maximum three times during the 22.5 years of this study . There were more males than females in all etiologic groups, with the ratio for the total patient population being 1.6:1 . The average age ranged between 11.7 and 16.5 years for all groups except for Haemophilus patients, who had a mean age of 2.5 years . The mortality rate was almost 55% for tuberculous patients and was approximately 40% for both pneumococcal and Haemophilus patients; it was 8.5% in patients with meningococcal disease.

J Forensic Sci, 1993 Jan, 38(1), 94 - 7
Invasive Haemophilus influenzae type B disease; Tepper SL et al.; Invasive bacterial disease due to Haemophilus influenzae is a cause of sudden death in children . It must be considered by medical examiners when a child dies with a fulminant course and nonspecific symptoms . Three fatal cases are presented in children 7 weeks to 15 months of age . Two had meningitis and petechiae or purpura . All three had bilateral adrenal hemorrhage and a rapidly fatal course . The potential for rapid and accurate diagnosis of H . influenzae infection is widely available due to latex agglutination technique against bacterial capsular wall antigens . Diagnosis is critical because of its public-health implications . Up to 50% of cases may be acquired in day-care settings . Chemoprophylaxis is recommended for household and day care contacts . With the recent introduction of Haemophilus b conjugate vaccines for routine administration to infants beginning at 2 months of age, a change in the epidemiology of the disease is anticipated.

Laryngoscope, 1993 Jan, 103(1 Pt 1), 33 - 41
Once-a-day therapy for sinusitis: a comparison study of cefixime and amoxicillin; Edelstein DR et al.; The efficacy and safety of a once-a-day antibiotic in the treatment of sinusitis was studied . Two randomly assigned groups were treated with either once-a-day cefixime, a third generation cephalosporin, or amoxicillin three times a day . One hundred and fourteen patients were evaluated with antral punctures, microbiologic evaluation, and radiographic studies . Cultures revealed 40% gram-negative organisms, 48% gram-positive, and 12% anaerobes . The most common bacteria were Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus and viridans group streptococci . Ninety-four percent of the cefixime group were cured compared with 96% of the amoxicillin group . Staphylococcus resistance was a problem in both groups, necessitating an occasional change to amoxicillin-clavulanate potassium in the amoxicillin group . Once-a-day antibiotics offer the potential for improved compliance in the treatment of sinusitis . Cefixime offers an additional benefit of covering beta-lactamase producing strains of bacteria which are increasing in incidence and resistant to many penicillins.

Laryngoscope, 1993 Jan, 103(1 Pt 1), 28 - 32
Subperiosteal orbital abscess in children: diagnosis, microbiology, and management; Skedros DG et al.; A chart review was undertaken of 30 patients who were presented to Children's Hospital of Pittsburgh from 1983 to 1990 and underwent surgical management for suspected subperiosteal abscess of the orbit (SPA) . All patients had preoperative computerized tomography (CT) scans . Twenty-seven of 30 CT scans were reevaluated, of which 20 (74%) demonstrated findings consistent with or suggestive of SPA . Opacified sinuses were seen in 100% of this study group . Abscess collections were found in 21 patients (70%) . Predominant organisms included: Streptococcus pneumoniae (38%), Streptococcus pyogenes (33%), and Haemophilus influenzae (14%); Moraxella catarrhalis was not isolated and anaerobic bacteria were isolated from only one patient . CT scans were found to be accurate predictors of SPA in 16 (80%) of 20 patients . All patients did well following surgical intervention without visual or central nervous system sequelae . We conclude from this study that CT scans should be obtained when SPA is suspected, and antimicrobial therapy should be directed toward the bacteria isolated from these abscesses.

Am J Dis Child, 1993 Jan, 147(1), 81 - 6
Efficacy of cefixime in the treatment of acute otitis media in children; Owen MJ et al.; OBJECTIVE--To compare the efficacy of cefixime with amoxicillin in the treatment of acute otitis media in children . DESIGN--Randomized, nonblinded study . SETTING--General pediatric clinic at a university hospital in Texas . PARTICIPANTS--A volunteer sample of 201 children, aged 2 months through 6 years . INTERVENTIONS--A 10-day oral course of cefixime (8 mg/kg per day administered once daily) or amoxicillin (40 mg/kg per day administered in three divided doses {every 8 hours}) . MEASUREMENTS/MAIN RESULTS--Tympanocentesis for bacterial culture was performed on all affected ears on enrollment and after 4 to 6 days of therapy . The patients were evaluated clinically 4 to 6 days after starting therapy, at the end of therapy, and 3 to 4 weeks after therapy was completed . Using Fisher's Exact Test, no significant difference was found between the two treatment groups for rate of clinical improvement or rate of eradication of Haemophilus influenzae and Streptococcus pneumoniae . However, combining the results from this study and two previously reported studies, cefixime was found to be more effective in eradication of H influenzae and less effective in eradication of S pneumoniae.

Postgrad Med, 1993 Jan, 93(1), 99 - 102, 105-6, 109-12
Adult meningitis . Rapid identification for prompt treatment; Vetter R et al.; To be effective, treatment of meningitis should be based on the history and physical examination, careful examination of the cerebrospinal fluid, and good clinical judgment regarding the most likely pathogen . Meningitis in adults is usually caused by certain common viruses and bacteria, although atypical pathogens should be considered in immunocompromised patients . Supportive therapy measures are appropriate for viral disease, and intravenous acyclovir (Zovirax) may be given if infection with herpes simplex virus is suspected . In cases of presumed bacterial meningitis, antimicrobial agents should be selected that penetrate the blood-brain barrier and maintain activity against the most likely pathogens; antibiotic therapy should be instituted right away, along with supportive measures . Although corticosteroids have proven benefits in the treatment of pediatric populations with Haemophilus influenzae meningitis, their effectiveness in adults has not yet been established . Prophylaxis with vaccines or rifampin is sometimes useful.

J Infect Dis, 1993 Jan, 167(1), 240 - 4
Antibiotic-induced bacterial killing stimulates tumor necrosis factor-alpha release in whole blood; Arditi M et al.; Rapid lysis of gram-negative bacteria is associated with considerable release of free endotoxin . Production of tumor necrosis factor (TNF) from adult whole blood ex vivo in response to bacterial products generated during antibiotic killing of Haemophilus influenzae type b (Hib) was investigated . Heparinized whole blood released TNF in a dose-dependent fashion in response to purified lipooligosaccharide of Hib . Bacteria (10(4)-10(7) cfu/mL) were placed into a Transwell filter insert (0.1 microns) and incubated with whole blood in the presence of various antibiotics . Exposure to ceftriaxone resulted in significantly greater release of TNF during killing of Hib than did exposure to imipenem, despite similar degrees of bacterial killing at 6 h . Polymyxin B inhibited the ceftriaxone-induced TNF release by 97%-99%, indicating that free endotoxin was the predominant stimulus for the increase in TNF release in this system . These observations suggest that ceftriaxone-induced killing of Hib results in bacterial cell wall products that are more proinflammatory than those produced by imipenem.

Infect Immun, 1993 Jan, 61(1), 91 - 6
Purification and partial characterization of the major outer membrane protein of Haemophilus somnus; Tagawa Y et al.; We purified the major outer membrane protein (MOMP), which is the most abundant OMP (with an apparent molecular mass of 40 kDa), from Haemophilus somnus strain 8025 . The method involves solubilization of the MOMP with Zwittergent 3-14 and further purification accomplished by ion-exchange and molecular-sieve chromatographies . The amino-terminal sequence of the MOMP showed considerable similarity to those of porin proteins from other gram-negative bacteria . The MOMP of H . somnus is immunogenic to rabbits and calves . Hyperimmune sera from rabbits and calves reacted with both the MOMP and lipopolysaccharides in enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis . The rabbit antiserum to the MOMP was cross-reactive with whole-cell preparations from strains 8025, D1238, NT2301, and 540 at a band with a molecular mass of 40 kDa in immunoblot analysis, although the reactivity of the rabbit antiserum with strain 540 was lower than those with the other strains tested . Two murine monoclonal antibodies (MAbs) to the MOMP were developed . ELISA with the OMP fractions as the antigens showed that one MAb was cross-reactive with the four strains but that the other MAb was reactive with the three strains other than strain 540 . These results indicate that the MOMP of H . somnus possesses at least two antigenic determinants and that the MOMP of strain 540 is antigenically different from those of the other strains . The antigenic heterogeneity of the H . somnus MOMP has implications regarding the development of a serotyping system with MAbs that is based on the MOMP epitopes.

Pediatr Infect Dis J, 1993 Jan, 12(1), 75 - 82
Review of cefixime in the treatment of otitis media in infants and children; Bluestone CD; During the past decade there has been an increase in the percentage of resistant bacteria isolated from middle-ear effusions aspirated from infants and children who have had acute otitis media . At least nine oral antibiotics or combination agents are available for this indication . Cefixime, a third generation cephalosporin, has excellent in vitro activity against both beta-lactamase-negative and beta-lactamase-positive Haemophilus influenzae and Moraxella catarrhalis, good activity against Streptococcus pneumoniae and Streptococcus pyogenes but relatively poor activity against Staphylococcus aureus . In children cefixime is similar in effectiveness to amoxicillin and cefaclor, but diarrhea and stool changes are more common with cefixime . Amoxicillin is still preferred for initial empiric treatment of uncomplicated acute otitis media . Its major drawback is limited efficacy when beta-lactamase-producing bacteria are the causative organisms . Cefixime is a viable alternative to amoxicillin for infants and children with acute otitis media when: (1) a beta-lactamase-producing H . influenzae or M . catarrhalis is isolated from otorrhea or tympanocentesis; (2) the child has a history of delayed hypersensitivity to the penicillins but no history of hypersensitivity to the cephalosporins; (3) there is a high incidence of resistant bacteria in the community; (4) there is not clinical improvement with amoxicillin; or (5) once daily administration is more convenient.

Pediatr Infect Dis J, 1993 Jan, 12(1), 70 - 4
Cefixime vs . cefaclor in the treatment of acute otitis media in children: a randomized, comparative study; Rodriguez WJ et al.; The efficacy of cefixime was compared with that of cefaclor in the treatment of 63 patients with acute otitis media . Patients received either a single dose of cefixime (8 mg/kg/day) or 3 divided doses of cefaclor (40 mg/kg/day) . On the basis of otoscopic and tympanometric results at 10 to 14 days after the start of treatment, 28 (97%) of 29 cefixime-treated patients and 25 (78%) of 32 cefaclor-treated patients had resolution of acute otitis media . The clinical cure rate associated with all organisms was 94% for cefixime (16 of 17 isolates) and 68% (13 of 19 isolates) for cefaclor . The cure rate for Streptococcus pneumoniae was 12 of 12 (100%) for cefixime and 7 of 7 (100%) for cefaclor; the cure rate for Haemophilus influenzae (which includes 2 patients with mixed infections) was 3 of 4 (75%) for cefixime and 2 of 7 (29%) for cefaclor . One clinical relapse occurred among 29 cefixime-treated patients; however, at 28 days 9 recurrences were observed . Three of 25 (9%) cefaclor-treated patients failed and 4 (13%) relapsed at 10 to 14 days, an additional 2 (10%) experienced recurrence by Day 28 . Eight (28%) cefixime-treated patients experienced adverse events (7 gastrointestinal and 1 diarrhea and rash); 8 (25%) cefaclor-treated patients experienced adverse events (all gastrointestinal) . Our data suggest that both at end of therapy and for 14 days thereafter, cefixime given once a day for acute otitis media is clinically equivalent to cefaclor given 3 times a day.

Pediatr Infect Dis J, 1993 Jan, 12(1), 62 - 9
Microbiologic and clinical aspects of a trial of once daily cefixime compared with twice daily cefaclor for treatment of acute otitis media in infants and children; Harrison CJ et al.; In this randomized, investigator-blinded multicenter study, tympanocentesis for acute otitis media with effusion in 137 ears from 108 children, 6 months to 12 years of age, revealed 84 definite pathogens and 32 potential pathogens . Twenty-nine aspirates from 23 subjects were sterile . Of the 116 isolates 42 (36%) were Streptococcus pneumoniae, 24 (21%) were Haemophilus influenzae, 9 (8%) were Moraxella catarrhalis, 9 (8%) were Streptococcus pyogenes and 1 (1%) was Staphylococcus aureus . Twenty-two (19%) definite pathogens produced beta-lactamase . Patients were randomized to cefixime (8 mg/kg/day daily) or cefaclor (40 mg/kg/day divided into two doses) . Efficacy was determined by pneumatic otoscopy and tympanometry at the end of therapy visit on Days 11 to 14 and up to 4 weeks of follow-up . At end of therapy subjects with definite pathogens exhibited a satisfactory clinical outcome in 26 of 36 (72%) ears for cefaclor and 40 of 48 (83%) ears for cefixime recipients (P = 0.12) . For ears with beta-lactamase-producing isolates there were no (0 to 12) cefixime failures but 4 of 10 cefaclor failures (P = 0.03) . Diarrhea/loose stools were more frequent in cefixime (16 of 58) than cefaclor (4 of 50) recipients . One cefixime subject required discontinuation of drug . Overall efficacy for treatment of acute otitis media with effusion was not different; however, cefixime appeared more effective for infections caused by beta-lactamase-producing organisms.

Otolaryngol Pol, 1993, 47(3), 253 - 63
{The role of haemophilus in respiratory tract diseases in children from Silesian Center of Children Rehabilitation in Rabka}; Kasprowicz A et al.; In this work the frequency of isolation of rods the genus Haemophilus from children suffering from various clinical sharpes of respiratory tract diseases . All isolated strains were tested in respect of species, biotype, the ability of adhesion to oral and laryngeal epithelia and their susceptibility to routinely applied antibiotics . A strong correlation between the species and biotype of rods from the genus Haemophilus and clinical shape of respiratory tract diseases was found . It was observed that the Haemophilus rods show differences in the ability of adhesion to oral and laryngeal epithelia . Only 52% of the isolated strains were susceptible to bactrim and 88% to tetracycline.

Pediatrie, 1993, 48(1), 37 - 49
{Antibiotherapy as first choice in infectious meningitis}; Cohen R et al.; The choice of antibiotics in bacterial meningitis must integrate several parameters . i) The bacterial epidemiology of community acquired meningitis: Haemophilus influenzae (Hi) Neisseria meningitidis (Nm), Streptococcus pneumoniae (Sp) represents more than 95% of cases; ii) The increase of antibiotic bacterial resistance, particularly preoccupying for Sp; iii) The microbiological properties and pharmacokinetics of antibiotics, especially their penetration in CSF: the concentrations achieved must be several times higher than the MBC . In fact, CSF is not favourable to the antibiotic activity; iv) The results of clinical comparative trials; v) The contribution of animal models to the knowledge of meningitis physiopathology . Third generation cephalosporins (cefotaxime, ceftriaxone) satisfy this objective for Hi, Nm, and penicillin sensitive strains of Sp . For penicillin resistant Sp, no treatment can achieve antibiotic CSF concentrations higher than ten times the MBC . An increase in dosage of cephalosporins, the use of an other regimen (Vancomycin or imipenem) and antibiotic association (rifamycin, fosfomycin) are needed.

Pediatrie, 1993, 48(1), 29 - 36
{Role of dexamethasone in the treatment of purulent meningitis in infants and in children}; Grimprel E et al.; Accumulating evidence tends to demonstrate that inflammatory processes are responsible for neurological damage and sequelae in bacterial meningitis in children and infants . Massive liberation of bacterial cell wall components (Lipopolysaccharide, acid teichoic polymers) induce a cascade of reactions including the secretion of many cytokines (such as TNF alpha and IL-1 beta) and prostaglandins (such as PAF and PGE2) which in turn leads to the development of cerebral oedema, intracranial hypertension and cerebral blood flow reduction . Dexamethasone (DXM) is effective at the beginning of the inflammatory cascade and its utilisation in the meningitis experimental model in animals has shown significant reduction in the inflammatory response to bacterial meningitis . The first clinical studies using DXM as an adjunctive therapy to antibiotics have demonstrated its beneficial effect in terms of complications and long-term neurological sequelae in Haemophilus influenzae meningitis in children and infants . It seems that a similar effect can be obtained in meningococcal and pneumococcal meningitis . Little information is actually available concerning the use of DXM in penicillin-resistant pneumococcal meningitis . The rare reported cases of ceftriaxone failure with DXM as treatment of penicillin-resistant pneumococcal meningitis had a favorable outcome with the use of vancomycin.

Pediatrie, 1993, 48(1), 11 - 6
{Duration of the treatment of meningitis except in the neonatal period}; Quinet B; Optimal treatment of bacterial meningitis raises three questions: which antibiotic? which dosage? which duration? The overall duration of antibiotherapy has been shortened since the last decade . If a short-course treatment shows similar efficacy and rate of relapse, unnecessary prolonged course of treatment exposes to increased cost, duration of hospitalization and secondary effects . From 1979, Gold et al in Toronto treated all uncomplicated cases of meningitis for seven days and obtained satisfactory results . The first randomized trials evaluating optimal duration of treatment in meningitis were performed in 1985 by Lin et al: they showed no difference in terms of efficacy and complications between conventional and short-term treatment . Current rules in meningococcal meningitis consist of seven days or less on therapy, and 7-10 days for pneumococcal or Haemophilus meningitis . The sequential follow-up of C-reactive protein (CRP) levels seems a useful tool for the management of bacterial meningitis.

Respiration, 1993, 60 Suppl 1, 10 - 5
Importance of beta-lactamase stability in treating today's respiratory tract infections; Cullmann W; In respiratory tract infections Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae and Klebsiella spp . are the most frequently encountered bacterial pathogens . Resistance of clinical S . pneumoniae isolates is known to be independent of beta-lactamase production, whereas resistance of the other species mentioned is due to beta-lactamase production . With respect to M . catarrhalis the first beta-lactamase-producing (bla+) isolate was detected in clinical specimens in 1976 and now, 70-90% of all clinical isolates are bla+ . The enzymes BRO-1 and BRO-2 are transposon-mediated thus explaining their rapid spread; they hydrolyze penicillin compounds very rapidly and, to a lesser extent, the older cephalosporins . Resistance in clinical H . influenzae isolates is mainly due to the prevalence of the most widespread transposon-mediated beta-lactamase, TEM-1, which has a substrate profile resembling that of the BRO enzymes . Bla+ H . influenzae isolates make up to 6% of the total in Northern Europe, in Southern Europe up to 55% and in many African countries more than 80% . More than 95% of Klebsiella spp . isolates possess a chromosomally encoded penicillinase and to a varying extent a plasmid-mediated enzyme in addition . Recently, reports from several countries have pointed to the clinical relevance of 'extended-spectrum enzymes' derived by point mutation from the 'classical' TEM-1 or TEM-2 enzymes . These new enzymes (TEM-3 to TEM-21) exhibit a broadened substrate profile, inactivating even the oxyiminocephalosporins . The most stable compounds are ceftibuten and cefetamet . With respect to the future, these enzymes may spread between species due to their location on transposons.(ABSTRACT TRUNCATED AT 250 WORDS)

Jpn J Antibiot, 1993 Jan, 46(1), 31 - 5
{Penetration into bone and joint tissues of rabbits and in vitro antibacterial activity of tosufloxacin}; Yamashiro Y et al.; The penetration of tosufloxacin (TFLX) into the bone and joint tissues of rabbits and its in vitro antibacterial activity were compared with those of lomefloxacin (LFLX) which is a efficacious drug for orthopedic infections . Serum levels of TFLX at 1, 2, 4 and 6 hours after oral administration (100 mg/kg) were 0.41, 0.65, 0.62 and 0.42 micrograms/ml, respectively . Except in synovial fluid and femur, TFLX concentrations in bone and joint tissues were higher than those in serum (0.69 approximately 1.92 micrograms/g in bone marrow of sternum, 0.55 approximately 1.53 micrograms/g in bone marrow of femur) . TFLX concentrations in synovial fluid at 4 and 6 hours after the administration were equal to those in serum, which were lower than those of LFLX, but the ratio of tissue level/serum level of TFLX was similar to that of LFLX . TFLX was 8- to 64-fold more active than LFLX against Staphylococcus aureus (including methicillin-resistant S . aureus), Streptococcus pyogenes, Haemophilus influenzae, which are major pathogens of purulent osteomyelitis and arthritis . TFLX inhibited the growth of these bacteria at less than 0.39 micrograms/ml . These results indicate that TFLX is a useful drug for orthopedic infection.

Vasa, 1993, 22(3), 247 - 50
Rupture of an aortic aneurysm caused by Haemophilus influenzae type B infection; Degener JE et al.; A patient was operated for a contained rupture of an aortic aneurysm that appeared to be infected with Haemophilus influenzae type b . Reports on this species as a cause of infection and rupturation of an atherosclerotic aneurysm are extremely rare and we therefore describe this case . Apparently the risk of bacteraemia and the possible effects of it in patients with an aneurysm should be considered in surgical decision-making and management.

Scand J Infect Dis, 1993, 25(3), 373 - 8
Susceptibility of respiratory tract pathogens in Finland to cefixime and nine other antimicrobial agents; Lehtonen L et al.; The in vitro activity of cefixime and 9 other orally used antimicrobial agents against 545 selected clinical respiratory tract pathogens was tested using the plate-dilution method . Of the strains tested, 144 were Haemophilus influenzae strains, 151 group A streptococci, 105 pneumococci and 145 Moraxella catarrhalis isolates . Ciprofloxacin was the most active drug, with a minimal inhibitory concentration (MIC) of < 0.06 mg/l for more than 87% of the isolates . With cefixime, a MIC of 0.06 mg/l inhibited 55% of the strains tested and a MIC of 1.0 mg/l inhibited all except one of the 545 strains . One pneumococcal strain was resistant to cefixime . Beta-lactamase producing H . influenzae and M . catarrhalis strains were clearly more susceptible to cefixime than to other oral cephalosporins (cephalexin, cefaclor, cefuroxime) . However, penicillin, ampicillin and cefuroxime were more effective against beta-hemolytic streptococci and pneumococci than was cefixime . The new third generation cephalosporin, cefixime, showed markedly better in vitro activity against certain major respiratory tract pathogens than the other peroral antimicrobials commonly used against respiratory tract infections.

Scand J Infect Dis, 1993, 25(3), 341 - 6
Deep obstetrical and gynecological infections caused by non-typeable Haemophilus influenzae; Kragsbjerg P et al.; Six patients with deep obstetrical and gynecological infections due to non-typeable Haemophilus influenzae are presented . 3 patients had tubo-ovarian abscesses, 2 septic abortions and 1 postpartum sepsis . All our patients with tubo-ovarian abscesses had used intra-uterine contraceptive devices until admission and all had a protracted course of illness . Both patients with septic abortion had a severe course, one of them with disseminated intravascular coagulation demanding treatment in the intensive care unit . The patient with postpartum infection had a milder course . The possibility of infection with H . influenzae and the emergence of beta-lactamase producing strains warrant adequate culture procedures in women with obstetrical and gynecological infections in order to ensure proper treatment.

Scand J Infect Dis, 1993, 25(3), 323 - 9
Erythromycin treatment is beneficial for longstanding Moraxella catarrhalis associated cough in children; Darelid J et al.; The benefits of antibiotic treatment and a nasopharyngeal culture in children with longstanding cough were analysed in a prospective randomized open study . Clinically suspected pertussis was excluded . Of 40 children given erythromycin for 7 days, 35 (88%) recovered in one week, compared with 17/47 (36%) untreated (p < 0.0001) . Erythromycin eliminated Moraxella catarrhalis from the nasopharynx in 21/31 children (68%), compared with spontaneous disappearance in 7/35 (20%) untreated controls (p < 0.001) . Purulent bronchitis or otitis media occurred in 2 children (5%) in the treatment group and in 21 (45%) in the control group (p < 0.01) . To evaluate the clinical role of isolated pathogens, the 47 untreated subjects were studied . Seven of 35 children harbouring M . catarrhalis recovered, compared with 8/12 in whom this bacterium was absent (p < 0.01) . No correlation was found between the isolation of Haemophilus influenzae or Streptococcus pneumoniae and the clinical outcome . Children with persistent cough > 10 days may benefit from erythromycin treatment . M . catarrhalis in the nasopharynx indicates prolonged symptoms and increased risk of bacterial complications.

Microbios, 1993, 74(299), 103 - 9
In vitro susceptibility of Haemophilus ducreyi to several antibiotics; Ismaeel NA; Haemophilus ducreyi was isolated from 59 (52%) of 113 men with a clinical diagnosis of chancroid . The following MIC50 (MIC90) values for H . ducreyi were obtained: erythromycin 0.14 (0.5) micrograms/ml, trimethoprim 0.25 (8.0) micrograms/ml, ceftriaxone 0.009 (0.14) micrograms/ml, and ciprofloxacin 0.007 (0.04) micrograms/ml . These data indicate that all isolates appear to be fully susceptible to erythromycin and the other antimicrobial agents tested, although ciprofloxacin was the most effective antibiotic.

Ophthalmologica, 1993, 206(2), 69 - 75
{Reproducible model of a bacterial conjunctivitis.}; Behrens-Baumann W et al.; To test the efficiency of antimicrobial substances on bacterial conjunctivitis under standardized conditions a reproducible model is needed . As there are no data in the literature concerning this topic we have developed a model of bacterial conjunctivitis in the rabbit eye . Instillation of a suspension of Haemophilus influenzae, Staphylococcus epidermidis or Staphylococcus aureus into the cul-de-sac did not result in any effect . Thus, standardized techniques of conjunctival incision were used additionally . A follow-up was done for a period of 2 weeks (degree of conjunctival hyperemia, microbiology) . Radial incision of the conjunctiva with injection of an S . aureus suspension (50 microliters of ATCC 29213; 1.35 x 10(8) cells) was done mimicking a branch injury . This resulted in a purulent conjunctivitis over a period of 1 week and disappeared within 14 days . The swabs were negative on day 7 . This is the first model establishing a reproducible purulent conjunctivitis in the rabbit . Using this model antimicrobial substances may be tested under standardized conditions.

Microbiol Immunol, 1993, 37(9), 671 - 7
Neutrophil response to nontypable Haemophilus influenzae in respiratory infections; Ahmed K et al.; Sputa from patients with respiratory infections by nontypable Haemophilus influenzae (H . influenzae) were investigated by electron microscopy . The cell wall of H . influenzae appeared wavy and nonwavy . In the cell wall the peptidoglycan layer was ill-defined . These patients had adequate IgG response in the serum against H . influenzae . However neither capsule nor fimbriae were found . Different stages of phagocytosis and destruction of the bacteria by polymorphonuclear neutrophils (PMN) were observed . PMNs were also found to phagocytose the debris . Evidences were found that the debris is formed mainly by the destruction of polymorphonuclear neutrophil . Extracellular lysosomes were also observed, which may have a role in destruction of both bacteria and host tissue . It was concluded that nontypable H . influenzae are nonfimbriated and noncapsulated during infection . Debris are the end product of PMN destruction, and phagocytosis of debris by PMNs has a role in the pathogenesis of chronic respiratory diseases.

Acta Vet Scand, 1993, 34(2), 193 - 8
Pathogenicity and immunity studies of Haemophilus parasuis serotypes; Nielsen R; After intranasal inoculation of SPF pigs with the 7 reference strains of Haemophilus parasuis only the reference strains of serotypes 1 and 5 proved to be pathogenic and were able to produce the lesions characteristic of Glasser's disease . Even though the reference strains of serotypes 2, 3, 4, 6 and 7 proved to be apathogenic, intranasal inoculation resulted in the development of circulating antibodies as demonstrated by the complement fixation test . This serological response suggests an antigenic relationship between serotypes 1 and 3 different from the relationship seen among serotypes 2, 4, 5, 6 and 7 . Pigs given an aerosol with the apathogenic serotypes 2, 3, 4 and 7, respectively, resisted challenge with a virulent Danish strain of serotype 5 . These results indicate that the 7 serotypes also have antigenic determinants in common and that these determinants elicit cross-protecting immunity on the respiratory mucosa.

Padiatr Grenzgeb, 1993, 31(4), 207 - 18
{Haemophilus influenzae meningitis in childhood}; Spencker FB et al.; From January 1971 until the end of 1989, 94 infants suffering from meningitis caused by Haemophilus influenzae were treated in the Department of Pediatrics of the University of Leipzig . The anamnestic data, signs and symptoms, laboratory findings, the courses and final results of treatment are described . 88 children survived; in eight of them neurological or mental sequelae were found on discharge . Generally, a certain stagnation regarding treatment results is observed over the observation period . Therefore vaccination against Haemophilus influenzae type B should be encouraged.

Nephron, 1993, 65(2), 196 - 205
Experimental immunoglobulin A nephropathy induced by gram-negative bacteria; Endo Y et al.; A study was conducted to determine whether intraperitoneal and oral administration of formalin-fixed gram-negative bacteria induced immunohistologically and ultrastructurally evident glomerular deposition of IgA and C3 in C3H/HeN mice . Separate treatments with strains of Pseudomonas aeruginosa, Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, and two kinds of lipopolysaccharide (LPS) were used . Two mice in each treatment group were sacrificed at 10, 20 and 30 weeks of age to examine sequential glomerular changes . In addition to the intraperitoneal administration (IP) groups receiving whole formalin-fixed bacterial cells, cell precipitate and supernatant fractions of each bacterial strain after sonication were injected intraperitoneally once a week, and the mice were sacrificed at 30 weeks of age . Sequential quantitation or IgG, IgA or IgM in serum and the isotypes specific for each of the bacterial strains or LPS administered was performed by ELISA . The incidence of immunofluorescence positivity for glomerular IgA and C3 was 37-71 and 37-66.7%, respectively, in the IP groups that had received bacterial cells of each strain, which was significantly higher than that in the IP groups given LPS or in the controls . These results suggest that cell wall components common among gram-negative bacteria, other than LPS, play a major role in the glomerular deposition of IgA and C3 . This is the first use of gram-negative bacteria to establish an active model of IgA nephropathy.

Vaccine, 1993, 11(10), 1003 - 6
Characterization of the serum antibody response induced by Haemophilus influenzae type b tetanus protein-conjugate vaccine in infants receiving a DTP-combined vaccine from 2 months of age; Barra A et al.; The serum antibody response induced by Haemophilus influenzae type b capsular polysaccharide (CPS)-tetanus protein conjugate vaccine combined to DTP vaccine was characterized in infants receiving three injections from 2 months of age . Sixty-five per cent and 94% of infants had anti-CPS antibody levels > or = 1 micrograms ml-1 after the second and third dose, respectively . The antibody response was mostly made up of IgG with a marked IgG1 predominance . Significant rises in bactericidal and in complement-mediated opsonic activities were observed after immunization . These data clearly show that this vaccine can be successfully administered in one syringe together with DTP vaccine during the regular infant immunization programme.

Immunodeficiency, 1993, 5(1), 1 - 21
Anti-capsular polysaccharide antibody deficiency states; Rijkers GT et al.; Antibodies directed to capsular polysaccharides form an essential component in the defence against infections with encapsulated bacteria such as Streptococcus pneumoniae and Haemophilus influenzae type b . Immune responses to polysaccharide antigens can occur in the absence of a functional thymus and the antigens are therefore designated as thymus independent . However, regulatory T cells may influence the magnitude of the antibody response to capsular polysaccharide antigens . So-called thymus independent type 2 antigens share several features of their immune response such as late development of antibody synthesis in ontogeny, no memory formation and a restricted isotype (IgM, IgG2) and idiotype usage . In infants and young children up to the age of 2 years the antibody response to capsular polysaccharides is inadequate resulting in an increased incidence of diseases such as pneumonia, meningitis, otitis and other forms of bacteremic disease . Anti-capsular polysaccharide antibody deficiency does occur in a number of well defined immunodeficiency syndromes including hypo- or agammaglobulinaemia, selective IgA and/or IgG subclass deficiency, Wiskott-Aldrich syndrome, DiGeorge anomaly and also in acquired immune deficiencies such as AIDS, and some forms of lymphoid malignancies . In elderly and in conditions such as splenectomy an increased incidence of infections with encapsulated bacteria does occur, sometimes but not always on basis of a defect in antibody formation . Clinicians are often confronted with young patients older than 2 years of age suffering from recurrent severe bacterial infections of the respiratory tract . In these patients no overt immunodeficiency is demonstrable but recent results indicated that a small percentage may show a selective defect in the antibody response since upon vaccination with polysaccharide vaccines no increase in antibody titer does occur . Though antibodies to polysaccharide antigens in young children are mainly of the IgM and IgG1 (IgG3) isotype, in older children and adults the polysaccharide antibodies are predominantly localized in the IgG2 subclass . The bridge between IgG2 type antibodies and phagocytosis of encapsulated bacteria is constituted by Fc gamma receptors for IgG2 on effector cells . The recent finding that allotypes of Fc gamma RIIa do exist that either bind or do not bind IgG2 type antibodies strongly suggests that the defence of a given individual to encapsulated bacteria apart from an intact antibody formation and the complement system also is determined by the allotype of the appropriate Fc gamma receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

Rev Latinoam Microbiol, 1993 Jan-Mar, 35(1), 87 - 90
{Detection of TEM-beta-lactamase in strains of Haemophilus influenzae resistant to ampicillin using the polymerase chain reaction (PCR)}; Espinosa de los Monteros LE et al.; With the purpose of determining the type of beta-lactamases that mediate ampicillin resistance to in Haemophilus influenzae strains in the Hospital Infantil de Mexico "Federico Gomez", we determined the minimum inhibitory concentration of 180 strains, isolated from different sources, to ampicillin, amoxicillin-clavulanic acid and ampicillin-sulbactam . All ampicillin resistant strains (29) were beta-lactamase positive as determined by nitrocephin hydrolysis . Using PCR with the primers from pBR322, we detected the presence of the gene for the TEM-beta-lactamase in 100% of the ampicillin resistant strains.

Zh Mikrobiol Epidemiol Immunobiol, 1993 Jan-Feb, (1), 57 - 62
{The effect of thymalin on the development of sensitization with a soluble microbial antigen and on the phenotypic composition of lymphocyte subpopulations in the organs of immunity}; Sukhodoeva GS et al.; The influence of thymalin on the formation of specific allergy and the distribution of immunocompetent cells in the immunity organs of guinea pigs immunized with Haemophilus influenzae antigen was studied . The stimulating influence of thymalin on the allergization of the body, changes in the lymphocyte subpopulations, as well as the possibility of the development of allergic reactions to thymalin, were established . Multiple injections of thymalin produced a stronger stimulating effect on the formation of specific microbial allergy and on the content of T- and B-lymphocytes than a single injection of the preparation.

Arch Vet Pol, 1993, 33(1-2), 89 - 105
Detection of the Haemophilus somnus antibodies in the bulls' reproductive tract fluids using the ELISA . II . Occurrence of specific antibodies in bulls from three Bull Rearing Centers; Stefaniak T; 301 seminal plasma samples, 212 preputial washings samples, and 173 blood serum samples were obtained from 242 bulls from the three Bull Rearing Centers (BRCs) (P, W, R) . The bulls were examined on their reproductive ability and depending on the result they were qualified to 4 groups . The H . somnus antibodies were detected in the IgG, IgM and IgA classes using ELISA . In seminal plasma the H . somnus antibodies were detected in the IgA (44.5%) and the IgG (4%) class . No antibodies were detected in the IgM class . In preputial washings the specific antibodies were detected in the IgA (42%), IgG (8.5%) and IgM (3.8%) classes . In blood serum the antibodies occurred in the IgG (76.9%), IgM (59.5%) and IgA (44.5%) classes . Between the particular BRCs and auction groups there were considerable, often significant, differences in the frequency of occurrence of the specific antibodies and the intensity of reactions found.

Arch Vet Pol, 1993, 33(1-2), 79 - 88
Detection of the Haemophilus somnus antibodies in the bulls' reproductive tract fluids using the ELISA . I . Elaboration of the ELISA for the detection of the specific antibodies in the IgG, IgM and IgA classes; Stefaniak T; The conditions of the ELISA for detecting the Haemophilus somnus antibodies in IgG, IgM and IgA classes were elaborated . The test was adapted for examining the seminal plasma, preputial washings and blood serum samples of bulls . In order to obtain the more precise evaluation of results, the tests were made for two different dilutions of the examined material . The arising out of this method difficulty in the evaluation of the intensity of reaction was solved by introducing the specific, semi-quantitative method of classification, using the eleven-degree scale . The mean arithmetic classificational values calculated from absorbance readings were called "absorbance index" . The introduced parameter proved to be especially useful while comparing the reaction of antibodies in reproductive tract fluids samples.

Kurume Med J, 1993, 40(4), 213 - 8
Clinical studies of oral quinolone once daily in the treatment of lower respiratory tract infections; Yano T et al.; The efficacy and safety of oral ofloxacin, 400 mg once daily, for the treatment of patients with lower respiratory tract infections were studied . The most common species recovered from the sputum specimens of these patients were Haemophilus influenzae, followed by Streptococcus pneumoniae (S . pneumoniae), Staphylococcus aureus (S . aureus), Gram positive cocci unidentified, Pseudomonas aeruginosa (P . aeruginosa), Morexella catarrhalis, Streptococcus epidermidis, and another Haemophilus species in this order . All these bacteria were susceptible to ofloxacin except for one strain of methicillin resistant S . aureus . A satisfactory clinical outcome was achieved in 34 of 40 patients (85%) . It is concluded that ofloxacin, 400 mg once daily, is useful for patients with respiratory tract infections.

Drugs, 1993, 45 Suppl 3, 98 - 101
Fluoroquinolones in the treatment of cystic fibrosis; Hoiby N et al.; Cystic fibrosis patients suffer from recurrent and chronic lung infections mainly caused by Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa . The fluoroquinolones, notably ciprofloxacin and ofloxacin, represent an important addition to the therapy of P . aeruginosa infections . They offer the possibility of effective oral treatment for early colonisation as well as chronic infections, even in children . They are associated with only few and mild adverse effects . Development of resistance represents an increasing problem.

Ann Trop Paediatr, 1993, 13(2), 153 - 8
Persistence of antibody at 18 months following vaccination of young Gambian infants with PRP-OMPC Haemophilus influenzae type b conjugate vaccine; Mulholland EK et al.; The rate of decline in anti-PRP antibody levels was measured in two groups of Gambian children who had been given PRP-OMPC at 1 and 3 months or 2 and 4 months of age . In the younger group (n = 70), the geometric mean titre fell from 1.32 micrograms/ml at 4 months to 0.44 micrograms/ml at 18 months . In the older group (n = 54), the geometric mean titre fell from 1.18 micrograms/ml at 5 months to 0.46 micrograms/ml at 18 months . The proportion of vaccinated children with antibody levels over 1.0 microgram/ml fell from 54% 1 month after the second dose of vaccine to 27% at the age of 18 months, while the proportion with levels over 0.15 micrograms/ml fell from 82% to 60%, with no significant differences observed between the vaccination groups . For those children who did not show evidence of environmental boosting, the half-life of anti-PRP antibody was about 100 days . This did not differ between the groups . These findings suggest that to provide lasting immunity PRP-OMPC should be given with a late booster dose at 12-15 months, as is the current practice in the USA . The need for a late booster dose may limit the value of this vaccine in developing countries where vaccination of children is difficult after the 1st year of life.

Ann Trop Paediatr, 1993, 13(2), 133 - 46
Seasonal variation of paediatric diseases in The Gambia, west Africa; Brewster DR et al.; In a 3-year prospective study of 9584 consecutive paediatric admissions to the Royal Victoria Hospital in Banjul, The Gambia, we examined the impact of seasonal variations in childhood diseases . The four principal diseases (falciparum malaria, pneumonia, gastro-enteritis and malnutrition) all peaked in September to October following the rainy season . The mortality rate was also higher in the rainy season than in the dry season . Of the 1525 children with cerebral malaria, 83% were admitted during the extended rainy season from July to December . With the emergence of chloroquine-resistant malaria over the 3 years, there was a 27% annual increase in severe anaemia owing to malaria . The median age of malarial anaemia (23 months) was significantly younger than that of cerebral malaria (42 months) . Malnutrition peaked immediately following the annual rainy season epidemics of bacterial gastro-enteritis but was not associated with the cool dry season rotavirus outbreaks . Rainy season diarrhoea was also associated with more persistent diarrhoea, an older mean age and a higher mortality . Meningitis was caused by either pneumococcus or Haemophilus influenzae in 64% of cases, of whom 19% were 0-2 months of age . Causes of death in hospital showed good agreement with Gambian community studies . We conclude that analysis of hospital data in a developing country can give accurate information on childhood morbidity and mortality patterns which can be used to set priorities for health care interventions . Seasonal variation is a cardinal feature of paediatric diseases in this part of Africa, and accentuates the vulnerability of children in poor families.

J Bacteriol, 1993 Jan, 175(1), 266 - 76
Purification and characterization of protein H, the major porin of Pasteurella multocida; Chevalier G et al.; Protein H (B . Lugtenberg, R . van Boxtel, D . Evenberg, M . de Jong, P . Storm, and J . Frik, Infect . Immun . 52:175-182, 1986) is the major polypeptide of the outer membrane of Pasteurella multocida, a bacterium pathogenic for humans and animals . We have purified this protein to homogeneity by size exclusion chromatography after selective extraction with surfactants and demonstrated its pore-forming ability after reincorporation into planar lipid bilayers . In these experiments, the current through the pores was a linear function of the applied voltage in the range of -50 to +50 mV . Voltages beyond +/- 50 mV tended to partially close the channels, giving rise to apparent negative resistances . These observations suggest that protein H channels are probably not voltage regulated in vivo . With the patch clamp technique, single-channel conductance fluctuations of 0.33 nS were recorded in 1 M KCl . Electrophoretic and circular dichroism analyses showed that protein H forms homotrimers stable in sodium dodecyl sulfate at room temperature, with a high content of beta-sheet secondary structure . Upon boiling, the trimers were fully dissociated into monomers with an increase of alpha helix and irregular structure, at the expense of beta sheets . The apparent molecular mass of fully denatured monomers ranged between 37 and 41.8 kDa, depending on the electrophoretic system used for analysis . The trimeric arrangement of protein H was confirmed by image analysis of negatively stained, two-dimensional crystal arrays . This morphological study revealed, in agreement with electrophoretical data, a trimeric structure with an overall diameter of 7.7 nm . Each monomer appeared to contain a pore with an average diameter of 1 nm . Quantitative comparisons revealed that the amino acid composition (hydropathy index of -0.40) and the N-terminal sequence (determined over 36 residues) of protein H are similar to those of bacterial general porins, notably porin P2 of Haemophilus influenzae . We conclude from this set of structural and functional data that protein H of P . multocida is a pore-forming protein related to the superfamily of the nonspecific bacterial porins.

Exp Clin Immunogenet, 1993, 10(3), 141 - 51
Rapid analysis of rearranged kappa light chain genes of circulating polysaccharide-specific B lymphocytes by means of immunomagnetic beads and the polymerase chain reaction; Hougs L et al.; Analysis of rearranged immunoglobulin genes used by B lymphocytes of known specificity is an important tool for the study of diversity and selection of B lymphocytes . Usually hybridoma cell lines are used for such analyses, but they are difficult to obtain from humans and may not be representative of the B lymphocytes activated in vivo . Here, we present a method for rapid analysis of the rearranged kappa light chain genes used by human circulating antigen-specific B lymphocytes . After vaccination with Haemophilus influenzae type b capsular polysaccharide (HibCP) conjugated with protein, the HibCP-specific B lymphocytes were isolated by antigen-coated immunomagnetic beads . After the purification, at least 98% of the immunoglobulin-secreting recovered cells were HibCP specific . The RNA was isolated and amplified by cDNA synthesis using a kappa constant region primer followed by polymerase chain reaction (PCR) using in addition a degenerate kappa light chain signal peptide region primer . The PCR product was cloned into the M13mp18 phage . The cloning efficiency was 100-600 clones/ml of blood . Of the 86 clones sequenced, 90% represented rearranged kappa light chain genes from different antibody-secreting cells . Examples of rearranged kappa genes used by HibCP-specific antibody-secreting cells from 4 adult vaccinees are given, representing the 3 largest of the 4 kappa variable region families . This method is a new tool for the investigation of vaccine-induced antibody responses with special reference to immunoglobulin gene usage and variability.

Ann Trop Paediatr, 1993, 13(4), 385 - 9
Antigenuria in healthy Papua New Guinean children with nasal Haemophilus influenzae type b carriage; Manary MJ et al.; In 100 healthy children under the age of 3 years living in the vicinity of Goroka, Papua New Guinea, the nares were cultured for Haemophilus influenzae type b (Hib), and a urine sample was obtained for measurement of Hib polysaccharide (PS) by ELISA . Hib carriage was detected in nine children and Hib PS was detected in the urine of 11 . Hib PS was found in seven of nine Hib nasal carriers compared with four of 91 healthy children without Hib in their nares (p < 0.001) . The range of urine antigen concentrations in the two groups was similar (0.6 to 2.7 ng/ml) . The relative risk of antigenuria in the carriers, compared with the children with negative nares cultures, was 58 (95% confidence interval, 10.5-324) . These data extend previous observations from Hib carriers studied in the United States and show that Hib carriage in children from a developing country is associated with antigenuria . Further studies are needed to determine whether carriers and patients can be differentiated by differences in the magnitude of the concentration of Hib PS excreted in urine.

JAMA, 1992 Dec 16, 268(23), 3350 - 2
Invasive Haemophilus influenzae infections in men with HIV infection; Steinhart R et al.; OBJECTIVE--To determine the incidence of invasive Haemophilus influenzae disease in men with the acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV) infection and the proportion of disease due to serotype b . DESIGN--Population-based, active surveillance . SETTING--San Francisco (Calif) Department of Health . PARTICIPANTS--All men 20 to 49 years of age with invasive H influenzae disease . RESULTS--The cumulative incidences of invasive H influenzae disease in men 20 to 49 years of age with AIDS and in HIV-infected men 20 to 49 years of age without AIDS were 79.2 and 14.6 per 100,000, respectively, but only 33% of cases were due to serotype b . The corresponding rates for invasive H influenzae b disease were 11.3 and 7.6 per 100,000 . CONCLUSIONS--Men with AIDS or HIV infection are at increased risk of invasive H influenzae infections, including H influenzae b, but such infections are still infrequent in this population.

FEMS Microbiol Lett, 1992 Dec 15, 79(1-3), 299 - 305
Serratia marcescens forms a new type of cytolysin; Braun V et al.; Most Serratia marcescens strains produce a new type of cytolysin (hemolysin) which is also found in other Serratia species . The hemolytic polypeptide ShlA (M(r) 162 101) is secreted across the outer membrane through the help of the ShlB protein which also involves conversion of an inactive precursor in an hemolytically active form . Both proteins are synthesized with signal sequences which are released during export across the cytoplasmic membrane . Mutants expressing inactive ShlB derivatives are impaired in activation and secretion suggesting a tight coupling between both processes . The region of ShlA for activation and secretion is confined to the N-terminal 16% of the polypeptide which contains the sequence NPNG which is also found in the Proteus hemolysin, the Bordetella pertussis filamentous hemagglutinin and two highly expressed outer membrane proteins of Haemophilus influenzae . Substitution of the first asparagine (N) residue by isoleucine converts the Serratia hemolysin into an inactive secretion incompetent form . It is concluded that this region is recognized by ShlB for activation and secretion of ShlA . The Serratia hemolysin forms defined pores in erythrocyte membranes.

FEMS Microbiol Lett, 1992 Dec 15, 79(1-3), 287 - 92
The sialylation of gonococcal lipopolysaccharide by host factors: a major impact on pathogenicity; Smith H et al.; The resistance of gonococci in most patients to complement mediated killing by human serum is due to sialylation of their lipopolysaccharide (LPS) which prevents bactericidal antibody from reacting with target sites . Two of the host factors responsible are: cytidine 5'-monophospho-N-acetyl neuraminic acid (CMP-NANA), a well-known sialylating agent, and another factor which enhances the transfer of sialyl groups from CMP-NANA to LPS catalysed by a gonococcal sialyltransferase . The bacterial determinant of resistance is a conserved LPS component of about 4.5 kDa which is sialylated at a terminal Gal beta 1-4GlcNAc site on its side chain . The sialylated LPS forms a surface coat which is stainable by ruthenium red and connected with previously described 'capsules' . These observations sparked off an explosion of research . Recent publications show that sialylation of LPS by CMP-NANA affects additional important aspects of gonococcal pathogenicity, notably interactions with antibodies and phagocytes, and rendering the gonococcal surface more 'host-like' . Also, the observations have prompted an examination of LPS from some other pathogens for the presence of sialyl groups with positive results for Neisseria meningitidis and Haemophilus influenzae.

J Immunol, 1992 Dec 15, 149(12), 3978 - 83
Effect of Haemophilus influenzae polysaccharide outer membrane protein complex conjugate vaccine on macrophages; Ambrosino DM et al.; Haemophilus influenzae type b polysaccharide-conjugate vaccines elicit protective antibody responses in young infants . One of these conjugates, polysaccharide linked to outer membrane protein complex (PRP-OMPC), is produced by linking the capsular polysaccharide to an outer membrane protein complex derived from group B Neisseria meningitidis . The outer membrane protein complex contains T cell carrier epitopes that elicit T cell-dependent antibody responses . OMPC also has been shown to increase the antibody response to other proteins administered concurrently that are not covalently linked (i.e., acts as an adjuvant) . In this study PRP-OMPC immunized mice demonstrated significant increases in spleen size as well as in splenocyte number as compared to saline controls (p < 0.01, p < 0.001, respectively) . No such increase was noted after immunization with another H . influenzae type b-conjugate vaccine, oligosaccharide linked to a variant of diphtheria toxin . By analytic flow cytometry, the mice immunized with PRP-OMPC demonstrated an increase in large splenocytes expressing the Ag Mac-1 (CD11b, CR3) . Furthermore, the spleens on histologic examination were characterized by an increase in the red pulp area consisting predominantly of cells of macrophage morphology . By immunohistochemical staining, the cells were identified as macrophages due to expression of Mac-1 and p150,95 (CD11C) Ag . After PRP-OMPC immunization, severe combined immunodeficient mice also demonstrated significant splenomegaly with an increase in macrophages identified by expression of Mac-1 and MHC class II Ag . Thus PRP-OMPC vaccine resulted in T cell-independent splenomegaly with an increase number of macrophages . We propose that this unique property may confer increased immunogenicity to PRP-OMPC through macrophage activation and cytokine release . Furthermore, the effect on macrophages may explain the "adjuvant" capacity of OMPC.

Can Commun Dis Rep, 1992 Dec 11, 18(23), 169 - 76
National Advisory Committee on Immunization (NACI) . Statement on Haemophilus influenzae type B conjugate vaccines for use in infants and children; A simplification of the enzyme-linked immunospot technique . Increased sensitivity for cells secreting IgG antibodies to Haemophilus influenzae type b capsular polysaccharide; Laboratory of Medical Immunology, Medical Department TTA, Rigshospitalet, Copenhagen, DenmarkA simplified enzyme-linked immunospot (ELISPOT) technique is described for the detection of cells secreting antibodies to tetanus toxoid (TT), diphtheria toxoid (DT) or Haemophilus influenzae type b capsular polysaccharide (PRP) . By combining the cell suspension with the enzyme-linked secondary antibodies in one incubation, the second incubation and washing procedure could be omitted from the original technique . The simplified assay had the same sensitivity for anti-TT and anti-DT spot-forming cells as the ordinary ELISPOT assay . The IgG anti-PRP spots were, however, improved both in quality and in quantity (median: 40% more spots), while the detection of IgM and IgA anti-PRP spot-forming cells was the same in the two techniques . This simplified technique can probably also be used to save time in other antigen systems and should be considered when designing ELISPOT assays for the detection of polysaccharide-specific antibody-secreting cells.

J Otolaryngol, 1992 Dec, 21(6), 434 - 6
Differential bacteriology in adenoid disease; Fearon M et al.; In order to define the differential bacteriology in adenoid disease, adenoids were obtained from 10 children with adenoid hypertrophy and 29 children with chronic adenoiditis . The patients' ages ranged from 18 months to 13 years . After removal of the adenoids, the surface organisms were destroyed by alcohol and flame disinfection . One gram of tissue was sampled for aerobic and anaerobic culture . There was an average of 4.8 isolates per specimen, with 4.2 aerobes and 0.6 anaerobes . The most common isolates were: Haemophilus influenzae (84%), diphtheroids (66%), non-pathogenic Neisseria species (66%), alpha-hemolytic streptococci (64%) and non-hemolytic streptococci (59%) . Anaerobes were present in 56% of all cases . The distribution of organisms was similar, regardless of clinical diagnosis . Only eight (21%) of the 39 cases had 'significant' (> or = 10(5) organisms/gm) colony counts . Our study detected no difference in either organism distribution or in total colony counts in chronic adenoiditis vs . adenoid hypertrophy.

Monatsschr Kinderheilkd, 1992 Dec, 140(12), 852 - 6
{Effectiveness of Haemophilus influenzae B-diphtheria conjugate vaccination in German children}; Zielen S et al.; BACKGROUND: In 1990 the Haemophilus influenzae b-Diphtheria conjugate vaccine (Hib-D) was introduced in Germany . In addition, most children under 18 months of age failed to develop protective levels of Hib antibodies in response to systemic infections . METHODS: To evaluate the protective efficacy of the Hib-D vaccine in Germany a post marketing case-control study was performed during 1.5 . 1990-30.4 . 1992 . Surveillance for invasive Hib-infections was maintained by pediatricians of 8 hospitals in the Rhein-Main area . The antibody responses to Hib were evaluated by ELISA at the onset (days 0-3) and during remission of disease . RESULTS: During the first year of the study 23 cases per 100,000 children of invasive Hib-infections were recorded . Of these children, 15 suffered from meningitis, 6 from epiglottitis and one from cellulitis and pericarditis respectively . None of these patients had been vaccinated except for one, who received two injections of Hib-D . Due to increased acceptance of the Hib-D vaccine we found a significant reduction of invasive Hib-infections (6 cases per 100,000 children) in the second year of the study . Again, of these children only one child was vaccinated . As expected, in all patients investigated the initial Hib antibody level was below 1 microgram/ml . The development of Hib specific immunity to invasive disease was clearly age dependent: 10 of 11 children below 18 months failed to produce any Hib antibodies (> 0.15 microgram/ml) in response to their infection . In contrast 8 of 10 children older than 18 months developed protective antibody levels to Hib . CONCLUSIONS: The incidence of serious Hib-disease has significantly decreased in Germany since the introduction of the Hib-D vaccine . Because no other Hib vaccine was licensed in Germany our data confirm efficacy and safety of Hib-D reported previously . In addition, children, who contracted disease before 18 months of age, remain susceptible to Hib and require active immunization for protection.

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