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| J Laryngol Otol, 1992 Dec, 106(12), 1072 - 5 Acute epiglottitis--25 years experience with nasotracheal intubation, current management policy and future trends; Andreassen UK et al.; During a 25-year period 168 adults and 111 children in Copenhagen County were treated for acute epiglottitis . Four patients, two children and two adults died, of these the two children and one adult had a cardiac arrest on arriving at the hospital . Most children were treated by nasotracheal intubation while only some adults required nasotracheal intubation in order to secure the airway . Our data indicate that intubation of adults with epiglottitis is technically more difficult than in children . The fibrelaryngoscope, a new diagnostic tool, is advocated, and was in this study used to establish the diagnosis in 12 unclear cases of acute epiglottitis . The incidence of acute epiglottitis in children was calculated at 3.2/100,000 with a minor annual variation . As vaccination against Haemophilus influenzae type b becomes more common, the incidence will probably be markedly reduced, maybe even eradicated in children, but in adults the same reduction cannot be expected as the causative agent in this group is less frequently Haemophilus influenzae type b. Antimicrob Agents Chemother, 1992 Dec, 36(12), 2804 - 7 Pharmacokinetics and tissue penetration of a single dose of ceftriaxone (1,000 milligrams intravenously) for antibiotic prophylaxis in thoracic surgery; Martin C et al.; The pharmacokinetics and tissue penetration of ceftriaxone after a single intravenous injection of 1,000 mg to 17 patients for antibiotic prophylaxis in thoracic surgery were studied . The patients were scheduled for elective noncardiac thoracic surgery . Adequate levels in serum (higher than or equal to the MIC for 90% of isolates of Staphylococcus aureus, Streptococcus spp., Escherichia coli, Haemophilus influenzae, and Klebsiella pneumoniae) were found for all patients throughout the surgical procedures . Mean maximal (5-min) and final (24-h) ceftriaxone levels in serum were 157 +/- 42 and 8.6 +/- 4.5 mg/liter, respectively . The beta-phase elimination half-life was 8.6 +/- 3 h, the plasma clearance was 18.4 +/- 6.25 ml/min, and the apparent volume of distribution at steady state was 0.21 +/- 0.07 liters/kg . At the time of the thoracotomy, the ceftriaxone concentrations were 13.5 +/- 7.8 micrograms/g in thoracic wall fat and 27 +/- 9 micrograms/g in lung tissue . At the time of closure, the ceftriaxone concentration was 15 +/- 9 micrograms/g in thoracic wall fat . During the different steps of the surgical procedures, 100% of patients had adequate levels in tissue (higher than or equal to the MIC for 90% of isolates of Streptococcus spp., E . coli, H . influenzae, and K . pneumoniae) . For S . aureus, 90 to 100% of patients had adequate tissue ceftriaxone levels. Tierarztl Prax, 1992 Dec, 20(6), 600 - 4 {Occurrence and drug resistance of bacteria pathogenic to the lungs from autopsy material of swine}; Kofer J et al.; Eight hundred and fifty-four piglets which died or were euthanized due to pneumonia or rhinitis atrophicans, were investigated during the period of 1986-1990 . Of the animals, 569 showed bronchopneumonia, 218 had pleuritis, pericarditis and peritonitis, 165 had rhinitis atrophicans, 58 pleuropneumonia, and 9 animals had fibrinous pneumonia . Pasteurella multocida, Haemophilus parasuis, Bordetella bronchiseptica, Actinobacillus pleuropneumoniae and Pasteurella haemolytica were isolated in 59.1%, 29.5%, 27.8%, 3.7%, and 2.3% cases of bronchopneumonia respectively . Samples from pigs with pleuritis or rhinitis atrophicans showed Pasteurella multocida in 63.8 and 68.5%, Bordetella bronchiseptica in 28.4 and 39.4%, streptococci in 28.9 and 3.9%, Haemophilus parasuis in 25.2% and 20.6%, Actinobacillus pleuropneumoniae in 5.1 and 5.5%, and Pasteurella haemolytica in 3.2 and 3.0%, respectively Actinobacillus pleuropneumoniae was found in 51 of 58 cases of pleuropneumonia and in 5 of 9 cases of fibrinous pneumonia; 55.6% and 44.4% respectively of those forms of pneumonia were positive for Pasteurella multocida . In the agar diffusion test, 36.8-82.6% of bacterial isolates showed resistance to streptomycin, 7.7-45.5% to sulfamethoxazole-trimethoprim, 5.7-44.6% to tetracycline, 0.2-32.8% to ampicillin, 0.0-16.3% to lincospectin, 2.0-81.2% to furazolidone, 0.4-4.5% to chloramphenicol, 1.3-78.1% to penicillin and 0-0.3% to enrofloxacin. Lymphokine Cytokine Res, 1992 Dec, 11(6), 293 - 8 Modulation of blood-brain barrier permeability by tumor necrosis factor and antibody to tumor necrosis factor in the rat; Kim KS et al.; In an attempt to understand the role of TNF in the central nervous system (CNS) pathophysiologic events associated with bacterial meningitis, we examined the effect of intravenous vs . intracisternal administration of TNF alpha on penetration of circulating 125I-labeled albumin into cerebrospinal fluid (CSF) and CSF white blood cell (WBC) counts in rats . Intracisternal administration of tumor necrosis factor alpha (TNF-alpha) resulted in dose- and time-dependent alterations of the CSF penetration and CSF WBCs, while intravenous administration of TNF-alpha did not induce any changes . These changes by intracisternal TNF were abolished by heat treatment of TNF or coadministration of MAb to TNF-alpha . Mab to TNF-alpha also significantly reduced the CSF penetration of circulating albumin in experimental hematogenous Haemophilus influenzae type b meningitis in infant rats but this salutary effect required both intravenous and intracisternal administration . However, MAb to TNF-alpha failed to affect CSF pleocytosis in experimental hematogenous meningitis . These findings suggest that some of CNS pathophysiologic changes in bacterial meningitis may be a result of the local production of TNF but other host inflammatory responses may also participate in CNS inflammation in hematogenous bacterial meningitis. West J Med, 1992 Dec, 157(6), 637 - 40 The effect of human immunodeficiency virus infection on the distribution and outcome of pneumonia in intensive care units; Tucker KJ et al.; To determine the frequency and distribution of pneumonia in an intensive care unit (ICU), we retrospectively examined the records of 1,854 consecutive ICU admissions between January 1987 and April 1990 . A total of 266 patients met criteria for pneumonia (unilateral or bilateral infiltrate by chest roentgenogram, plus 2 of the following: leukocyte count > 10 x 10(9) per liter, temperature > 38.5 degrees C, or culture of blood or sputum positive for pathogens) . Pneumocystis carinii pneumonia in patients infected with the human immunodeficiency virus was the most frequent cause (28%) precipitating an ICU admission in this series of patients . Streptococcus pneumoniae (13%), Staphylococcus aureus (8%), Haemophilus influenzae (4%), and viruses (4%) were also commonly observed . Overall mortality was 20% . An APACHE II score of greater than 24, the need for intubation, and the presence of P carinii were predictive of increased mortality . Age, sex, and length of stay did not predict final results . Patients with P carinii pneumonia who required intubation had an overall mortality of 54%, which was higher than patients without P carinii pneumonia who required intubation (P < .05) . Our experience shows the changing spectrum of pneumonia in ICUs . In contrast to reports of a decade ago in which S pneumoniae and Pseudomonas aeruginosa are cited as most common, P carinii is now most prevalent in our ICU . Although our findings reflect the increasing incidence of human immunodeficiency virus infection in San Francisco, California, they may also be pertinent to other areas in the United States where the incidence of this infection continues to increase. J Paediatr Child Health, 1992 Dec, 28(6), 459 - 64 The epidemiology of acute epiglottitis in children in Western Australia; Hanna JN et al.; A comprehensive case definition was used to study all cases of epiglottitis that occurred in children under 15 years of age in Western Australia during a 5 year period . There was microbiological evidence of Haemophilus influenzae type b infection in 71% of 103 cases of epiglottitis . Seventy-five per cent of cases occurred in children under 5 years of age . In this age group, the estimated annual incidence (13.5 episodes per 100,000) was significantly lower than that reported in Victoria (22.7 per 100,000) . The case definition of invasive H . influenzae type b disease used for surveillance purposes in Canada was more sensitive than the definitions used in the United States or England and Wales, yet even the Canadian definition could have detected only 65% of the cases of epiglottitis that occurred in Western Australia . A simple and sensitive surveillance system which could be used to monitor the impact of H . influenzae type b immunization in Western Australia is proposed. J Learn Disabil, 1992 Dec, 25(10), 630 - 8 Academic achievement following childhood brain disease: implications for the concept of learning disabilities; Taylor HG et al.; The present study examined three hypotheses regarding the consequences of early brain damage for academic achievement: First, early brain insults will have a negative impact on achievement, even in children with normal intelligence . Second, underachievement in these children will be at least partially independent of IQ (i.e., not fully accounted for by a lowering of IQ within the average range) . Third, normally intelligent children with histories of brain insult will also manifest selective cognitive dysfunctions . To test these hypotheses, we compared two groups of children who had recovered from Haemophilus influenzae type b meningitis . The "complicated" group consisted of children who, as a consequence of having sustained neurologic complications during their illness, were more likely to have had brain insults . Children in the "uncomplicated" group did not have complications with their illness and were regarded as having escaped significant central nervous system (CNS) pathology . Only children with normal hearing and a prorated Full Scale IQ of at least 80 (WISC-R) were considered . Group differences on the Wide Range Achievement Test-Revised were consistent with the first two hypotheses . Although the two groups had similar Verbal IQs, the complicated group also had a lower mean Performance IQ and performed less well on perceptually demanding neuropsychological tasks . Findings suggest that learning disabilities may have selective, brain-related cognitive antecedents; but they challenge the practice of using IQ criteria for clinical diagnosis. Ann Emerg Med, 1992 Dec, 21(12), 1413 - 7 Utility of serum interleukin-6 for diagnosis of invasive bacterial disease in children; Saladino R et al.; STUDY OBJECTIVE: To evaluate measurement of interleukin-6 as a diagnostic test for the presence and severity of invasive bacterial disease . DESIGN: Prospective measurement of interleukin-6 in children with signs of sepsis . (Controls, retrospective from serum bank.) SETTING: Emergency department of an urban children's hospital . PARTICIPANTS: Twenty children with clinical signs of sepsis and 50 other febrile infants and toddlers with negative blood cultures . RESULTS: Eleven of the 20 patients had bacteriologically documented infections: four with meningitis and two with bacteremia caused by Neisseria meningitidis, three with meningitis caused by Haemophilus influenzae type b, and one each with meningitis and bacteremia caused by Streptococcus pneumoniae . Ten of these 11 had detectable interleukin-6 . The geometric mean interleukin-6 level in these culture-positive patients was 407 pg/mL (95% confidence interval, 108 to 1,545); all three children with levels of more than 300 pg/mL developed septic shock, and one died . One of nine culture-negative patients with clinical signs of sepsis had detectable serum interleukin-6 (166 pg/mL), but none of 50 other febrile children without occult bacteremia did . The detection of interleukin-6 had a sensitivity of 91% and a specificity of 98% for invasive bacterial disease . CONCLUSION: High levels of interleukin-6 occur in children with septic shock, and the presence of interleukin-6 in serum is predictive for the isolation of bacteria from blood and/or spinal fluid. J Infect Dis, 1992 Dec, 166(6), 1340 - 5 Changes in the distribution of Haemophilus influenzae type b clones associated with widespread infant vaccination in Finland; van Alphen L et al.; Isolates from 646 consecutive Finnish Haemophilus influenzae type b (Hib) patients with systemic disease, collected before and during large-scale vaccinations with Hib conjugate vaccines, were analyzed by major outer membrane protein (OMP) subtyping, lipopolysaccharide (LPS) serotyping, and biotyping (BT) . Strains with OMP-BT-LPS combinations (clones) 1-I-1 and 1c-I-1 disappeared at the same rate as the disease they were associated with . A preferential decrease in the number of isolates of clone 1-II-1 was recorded, whereas the reduction in disease caused by strains of clone 1-II-9 occurred at a lower rate than expected . The latter clone occurred mainly in the most densely populated area of Finland . Strains belonging to all the common Hib clones were isolated from the 16 infants who acquired Hib disease despite being (partially) vaccinated . Thus, Hib clones disappeared during mass vaccination with conjugate vaccines, although at different rates. J Infect Dis, 1992 Dec, 166(6), 1335 - 9 Characterization of the serum antibody response to the capsular polysaccharide of Haemophilus influenzae type b in children with invasive infections; Trollfors B et al.; The serum antibody response to the capsular polysaccharide of Haemophilus influenzae type b (Hib) was studied in 30 children aged 1 day-5 years with invasive Hib infections . From each child, serum was obtained 0-2 days, 5-11 days, 1 month, and 6-12 months after onset of symptoms . Total antibodies were determined with RIA and isotypes with ELISA . Only 2 children had antibody levels above the estimated protective level (0.15 microgram/mL) in the first serum sample . The antibody response was age dependent with wide individual variations . Children > or = 2 years had increases in IgG, IgM, and IgA antibodies with predominance of IgG . The initial IgG response was IgG1 and IgG2 with predominance of IgG1 . In the last serum sample, IgG1 antibodies had decreased while IgG2 antibodies remained unchanged . Only 2 of 7 children < 1 year had a detectable antibody response . The correlation coefficient for total antibodies compared with the sum of IgG, IgM, and IgA was .88 (P < .0001) and for IgG compared with the sum of IgG1 and IgG2 was .97 (P < .0001). Occas Pap R Coll Gen Pract, 1992 Dec, (58), 21 - 3 Chronic obstructive airways disease; Hetzel M et al.; 1 . Chronic obstructive airways disease is a term which should be reserved for those who have objective evidence of airways obstruction and who do not improve significantly with bronchodilators or steroids . All patients should have a trial of aggressive treatment with these drugs in case they have chronic asthma . 2 . All patients should be urged strongly to give up smoking . 3 . There is no scientific evidence that slow release aminophylline or theophylline are of benefit in these patients, and they may be hazardous in those with coronary artery disease . 4 . Acute infective exacerbations may be due to haemophilus influenzae or pneumococcus; patients with fever should be given co-trimoxazole, ampicillin, co-amoxiclav or erythromycin (co-trimoxazole should generally be avoided in the elderly) . 5 . Domiciliary oxygen therapy, given for at least 12 and preferably 16 hours a day, will prolong survival in patients with Type II respiratory failure ('blue bloaters') . It may help symptoms in Type I respiratory failure ('pink puffers') . It should only be prescribed after blood gas measurements and the patient must therefore be referred. Genetics, 1992 Dec, 132(4), 893 - 8 DNA repair and the evolution of transformation in Haemophilus influenzae; Mongold JA; Under certain environmental conditions, naturally transforming bacteria are induced to pick up DNA released into the environment by other cells of the same or closely related species and, by homologous recombination, integrate that DNA into their chromosome . The selective pressures responsible for the evolution and maintenance of this form of genetic outcrossing, or sex, in bacteria are not known . A prominent hypothesis is that transformation, and sex in general, evolved as a means of obtaining DNA templates to repair damaged regions of the chromosome . Previous results obtained with Bacillus subtilis were consistent with the repair hypothesis . In an effort to explore the generality of those results, I have tested the repair hypothesis with Haemophilus influenzae, a naturally transforming, gram-negative species of bacteria . The results of UV damage-survivorship experiments with H . influenzae were also consistent with that hypothesis . However, additional experiments demonstrate that the higher survival of transformed cultures cannot be accounted for by use of the transforming DNA as templates for repair . I consider alternative hypotheses for the means by which transformation can increase cell survival following UV exposure and discuss the implications of these results with respect to the DNA repair hypothesis and the evolution of transformation. Zentralbl Bakteriol, 1992 Dec, 277(4), 538 - 46 Adjuvant properties of Propionibacterium avidum KP-40 in vaccination against endemic viral and bacterial infections . II . Swine immunized with inactivated Haemophilus pleuropneumoniae vaccine and experimentally infected with different virulent serotypes of H . pleuropneumoniae; Markowska-Daniel I et al.; Forty 3-month old swine were treated with immunomodulating Propionibacterium avidum KP-40 (PA) and/or vaccinated with a formalin-inactivated mixture of serotypes 1, 3, 5 and 9 of Haemophilus pleuropneumoniae (Pleurovac) . Three weeks after revaccination all animals were inoculated with viable single serotypes of Haemophilus pleuropneumoniae . The IgG antibodies induced by vaccination agglutinated all serotypes of Haemophilus pleuropneumoniae, except for serotype 5 . Antibody titers were not influenced by the application of PA together with the vaccine . Infection of vaccinated piglets resulted in the development of pleuropneumonia in 8 out of 10 animals, while vaccination together with application of PA lowered the morbidity rate to 1 out of 10 (p < 0.05) . The usefulness of a PA prophylaxis was also demonstrated in non-vaccinated piglets infected with Haemophilus pleuropneumoniae . Because of the considerable variability of strains and serotypes of Haemophilus pleuropneumoniae and the generally low prophylactic potency of pleuropneumonia vaccines it is concluded that long-lasting enhancement of non-specific antiinfective resistance caused by PA may lower the risk of endemic infections in vaccinated piglets. Oral Microbiol Immunol, 1992 Dec, 7(6), 376 - 7 Evaluation of the E test for antimicrobial susceptibility testing of Actinobacillus actinomycetemcomitans; Pajukanta R et al.; The E test was compared with an agar dilution method for antimicrobial susceptibility testing of Actinobacillus actinomycetemcomitans on Mueller-Hinton Haemophilus test medium . Eighty recent isolates of A . actinomycetemcomitans from 40 subjects and 3 reference strains were studied . Excellent agreement was obtained between the E test and the agar dilution test for benzylpenicillin (98.8%), ampicillin (97.5%), cefaclor (100%), cefuroxime (100%), tetracycline hydrochloride (100%) and ciprofloxacin (98.7%); 76.0% agreement was obtained for metronidazole and only 5.2% for cotrimoxazole . This study indicates that the E test is a reliable method to determine minimal inhibitory concentrations of antimicrobials against A . actinomycetemcomitans, except for metronidazole and cotrimoxazole. Acta Paediatr, 1992 Dec, 81(12), 989 - 92 Role of non-capsulated Haemophilus influenzae as a respiratory pathogen in children; Korppi M et al.; During a 12-month surveillance period from 1981-1982, non-capsulated Haemophilus influenzae was detected in nasopharyngeal aspirates from 64 (14%) of the 449 children hospitalized for middle or lower respiratory infection . An antibody response to H . influenzae was indicated in 15(23%) of the 64 patients with H . influenzae present in nasopharyngeal aspirate and in 10 (3%) of the 385 patients with a negative finding . Thus, serological evidence of H . influenzae infection was demonstrated in 25 (6%) of all the 449 children with respiratory infection . Of 13 patients with cultures positive for H . influenzae acute otitis media, an antibody response was seen in only 4 (30%) patients . H . influenzae infection was associated with infections caused by other microbes in 20 children (80%), with viral infections in 60% and with pneumococcal infections in 24% of cases . An infection focus was present in 15 (79%) of the 25 patients with H . influenzae infection; pneumonia was present in 10 cases and acute otitis media in 9 cases . Non-specific laboratory evidence of bacterial infection was seen in 11 patients (58%); C-reactive protein was increased in 7 and erythrocyte sedimentation rate in 9 patients . It is concluded that non-capsulated H . influenzae is a genuine respiratory pathogen in children . H . influenzae infections appear to be secondary to preceding viral or other bacterial infections in children who are carriers of this strain. Jpn J Antibiot, 1992 Dec, 45(12), 1700 - 35 {Pharmacokinetic and clinical studies on cefprozil granules in the pediatric field}; Motohiro T et al.; Cefprozil (CFPZ), a newly developed oral cephalosporin in a fine granular form for pediatric use, was administered to children with bacterial infections . MICs were determined for 6 drugs including CFPZ, cephalexin (CEX), cefaclor (CCL), ampicillin (ABPC), methicillin (DMPPC) and cloxacillin (MCIPC) against the following 84 strains isolated from cases to which CFPZ was administered; 55 strains of Gram-positive cocci (GPC) including 2 strains of Staphylococcus aureus, 49 strains of Streptococcus pyogenes, 4 strains of Streptococcus pneumoniae, and 29 strains of Gram-negative bacilli (GNB) including 10 strains of Haemophilus influenzae, 18 strains of Escherichia coli, and 1 strain of Proteus mirabilis . MIC determination of these strains was done with an inoculum size of 10(6) CFU/ml . In pharmacokinetic studies, serum concentrations, urinary concentrations and urinary recovery rates were investigated using bioassay and high-performance liquid chromatography (HPLC) . CFPZ was orally administered 30 minutes before meals to 9 children with ages ranging from 7 years and 1 month to 12 years and 3 months . Three groups of 3 children were tested with doses of 4.0, 7.5 and 15.0 mg/kg, respectively . In addition to the above, clinical and bacteriological studies were performed in a total of 160 cases consisting of children with ages ranging 5 months to 12 years and 5 months . A mean dose of 8.6 mg/kg in 3-4 divided doses (130 cases of t.i.d . and 30 cases of q.i.d.) was administered for an average of 7 days . The 160 cases included 34 cases of pharyngitis, 5 cases of tonsillitis, 8 cases of acute bronchitis, 8 cases of pneumonia, 52 cases of scarlet fever, 4 cases of acute purulent otitis media, 47 cases of urinary tract infection, 1 case of purulent lymphadenitis and 1 case of posthitis . Adverse reactions and abnormal clinical laboratory test results were also examined in 166 cases, including 6 cases excluded from the evaluation of clinical efficacy . The results obtained are summarized as follows: 1 . With regard to GPC, MICs of CFPZ against 2 strains of S . aureus were 0.78 or 1.56 micrograms/ml and CFPZ showed the second highest activity to MCIPC . MICs of CFPZ against 49 strains of S . pyogenes were all less than 0.025 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS) Jpn J Antibiot, 1992 Dec, 45(12), 1642 - 9 {Clinical studies on cefprozil granules}; Haruta T et al.; Cefprozil granule preparation was administered orally to 16 patients (ages ranging 8 months to 9 years and 6 months) with pediatric bacterial infections at daily dose levels between 29.4 and 35.7 mg/kg divided into 3 or 4 doses . The following results were obtained . 1 . Sixteen patients including 5 with pharyngitis, 3 with tonsillitis, 3 with lacunar tonsillitis, 2 with pneumonia, 2 with contagious impetigo and 1 with scarlet fever were treated . Clinical effects were excellent in 9 cases and moderate in 7, with an overall efficacy rate of 100% . 2 . Organisms suspected as pathogens included 17 strains (10 strains of haemophilus influenzae, 2 of Haemophilus parainfluenzae, 3 of Streptococcus pyogenes and 2 of Staphylococcus aureus) . Bacteriologically, eradication of pathogens were observed for 11 strains, but no changes were obtained for 5 (all Haemophilus), and unknown results were obtained for 1, thus the eradication rate was 68.8% . 3 . No side effects were observed . Abnormal laboratory test results included 2 cases of increase in platelets, and 2 of increase in eosinophils, but those were not significant . 4 . No refusal of the drug occurred due to its taste or odor. Oral Microbiol Immunol, 1992 Dec, 7(6), 372 - 5 Rapid identification of Actinobacillus actinomycetemcomitans based on analysis of 23S ribosomal RNA; Preus HR et al.; Actinobacillus actinomycetemcomitans is a key microorganism in the pathogenesis of several different forms of periodontal diseases . Identification of this bacterium from clinical specimens may often be complicated by the fact that the colony morphology on TSBV selective medium closely resembles that of Haemophilus aphrophilus and a key differentiating characteristic, catalase reaction, may be variable . Recent genetic studies have shown that the 23S ribosomal RNA molecule is split into two smaller forms in A . actinomycetemcomitans, but is intact in H . aphrophilus . Based on this finding, we describe a new, rapid method for identifying A . actinomycetemcomitans in which single colonies isolated from culture on TSBV agar in 5% CO2 in air are lysed, electrophoresed on 1.5% submarine agarose gels and visualized by staining with ethidium bromide . Using this assay, A . actinomycetemcomitans can be easily distinguished from morphologically similar colonies such as H . aphrophilus strains by differences in 23S rRNA within 2 h. J Med Microbiol, 1992 Dec, 37(6), 413 - 9 Identification of highly conserved and species-specific polypeptides of Haemophilus ducreyi; Alfa MJ et al.; Chancroid is a sexually transmitted diseased caused by Haemophilus ducreyi . The pathological manifestations of chancroid are unique among Haemophilus species and the virulence factors of H . ducreyi that account for these features have not been identified . Some of these virulence factors may be unique components of H . ducreyi, but attempts to identify H . ducreyi-specific components have been unsuccessful . Four polypeptides--A, B, C and D of 83, 77, 56 and 28 kDa, respectively--were identified with a panel of nine H . ducreyi-specific monoclonal antibodies (MAbs) . Polypeptide C was one of the five major proteins in H . ducreyi and demonstrated micro-heterogeneity in SDS-PAGE . Polypeptides A, B and D were present in only small amounts in whole-cell lysates of H . ducreyi . The relative amounts of A and B varied, suggesting that they may be precursor molecules . The unique polypeptides C and D were not exposed on the surface . Polypeptide C was highly soluble and did not appear to be membrane-bound, whereas polypeptide D appeared to partition with the cytoplasmic membrane and was soluble in Sarkosyl . All four polypeptides appeared to be unique to H . ducreyi since MAbs directed against them did not cross-react with H . influenzae, H . parainfluenzae or Neisseria gonorrhoeae . The mol . wts of all of these polypeptides were conserved throughout 35 clinical isolates collected from 15 cities in eight countries and one reference strain of H . ducreyi that were tested.(ABSTRACT TRUNCATED AT 250 WORDS) Infect Immun, 1992 Dec, 60(12), 5204 - 11 Molecular analysis of the P2 porin protein of nontypeable Haemophilus influenzae; Sikkema DJ et al.; The P2 porin protein is the most abundant outer membrane protein (OMP) of nontypeable Haemophilus influenzae (NTHI) and shows extensive antigenic heterogeneity among strains . To study the molecular basis of this heterogeneity, the DNA sequences of the genes encoding the P2 proteins of three unrelated strains of NTHI were determined, and restriction fragment length polymorphisms around the P2 genes of 35 strains were analyzed . The deduced amino acid sequences of the P2 genes from the three strains of NTHI revealed four major (12 to 35 amino acids long) and several smaller (2 to 7 amino acids) hypervariable regions in each protein . The major variations occurred in identical portions of the genes, and these regions showed a high antigenic index and surface exposure probability in computer modeling analysis . Differences in the molecular mass of the P2 protein correlate with differences in the size of the variable region in each strain . Oligonucleotide primers suitable for amplification of the P2 genes by polymerase chain reaction were developed . Restriction fragment length polymorphism analysis showed marked heterogeneity in and around the ompP2 locus of 35 NTHI strains . These results contrast with the high degree of conservation of the P2 genes in H . influenzae type b strains . We conclude that the molecular mass and antigenic heterogeneity of the P2 molecule of NTHI is due to variations in gene sequence that are clustered primarily in four large hypervariable regions of the gene. Tidsskr Nor Laegeforen, 1992 Nov 30, 112(29), 3684 - 7 {Treatment of bacterial meningitis in children}; Flaegstad T; The treatment of children with bacterial meningitis includes many aspects, such as fluid and antibacterial therapy, treatment of convulsions, and prophylactic use of dexamethasone . This report focuses in particular on the prophylactic use of dexamethasone together with cefalosporines in order to reduce inflammation and neurological sequelae in this disease . Probably this approach is now justified in the treatment of meningitis caused by Haemophilus influenzae . Modern principles for fluid therapy and treatment of increased intracranial pressure are also discussed. Jpn J Antibiot, 1992 Nov, 45(11), 1592 - 608 {Overall clinical evaluation of cefprozil against infections in pediatric fields . Pediatric Study Group for Cefprozil}; Fujii R et al.; Cefprozil (CFPZ, BMY-28100) granule preparation was studied for pharmacokinetic, bacteriological and clinical aspects in the pediatric infections . The results obtained are summarized as follows: 1 . Serum concentrations and urinary excretion . The pharmacokinetics of CFPZ in pediatrics was investigated by single oral administration of fine granules at doses of 4.0, 7.5 and 15.0 mg/kg . Peak blood levels of CFPZ were 3.06, 4.62 and 9.65 micrograms/ml, respectively, at 1.00-1.30 hours after each dose and AUCs were 7.44, 12.50 and 27.01 micrograms.hr/ml, respectively . These data showed that Cmax and AUC depended on dose levels . T 1/2 (beta) at these dose levels were 1.03, 0.94 and 1.01 hours, respectively . There were no differences related to dose . Urinary recovery rates in the first 6 hours after administration were 51.5-57.1% . The pharmacokinetics of CFPZ before or after meals were also investigated at a dose of 7.5 mg/kg . Peak blood levels were 4.88 micrograms/ml at 1.17 hours after administration in the fasting state, and 4.30 micrograms/ml at 1.54 hours after administration in the non-fasting state . Delay of Tmax and slight decrease of Cmax were observed in the non-fasting state, but T 1/2 and AUC were 0.91 hour and 12.96 micrograms.hr/ml, respectively, in the non-fasting state, and were similar to those in the fasting state, 0.93 hour and 12.82 micrograms.hr/ml, respectively . Urinary recovery rates in the first 6 hours after administration were 63.8% in the fasting state and 50.7% in the non-fasting state . 2 . Clinical results . Clinical efficacies of CFPZ granules in various infectious diseases were studied in 804 cases . Twenty nine cases, mostly viral or mycoplasmal infections, were excluded from the statistical analysis . The clinical efficacy rate in 527 cases with causative bacteria isolated was 97.2%; and in 248 cases from whom no significant isolate had been obtained was 96.0% . The clinical efficacy rate in 475 cases with monobacterial infections (proven by culture of isolates) was 97.3%, and that in 52 case with polybacterial infections was 96.2% . Haemophilus influenzae was isolated mostly from acute respiratory infections . In 88 cases from whom H . influenzae was isolated, clinical efficacy rate was 95.5% . In cases from whom H . influenzae was found concomitant by with Staphylococcus aureus, Streptococcus pyogenes or Streptococcus pneumoniae, the clinical efficacy rates were also high . The bacteriological eradication rate in cases with 582 strains was 83.3%; the eradication rate for Gram-positive organisms was 95.8%; and for Gram-negative organisms, it was 64.2%.(ABSTRACT TRUNCATED AT 400 WORDS) Jpn J Antibiot, 1992 Nov, 45(11), 1571 - 81 {Pharmacokinetic, bacteriological and clinical studies on cefprozil in pediatric patients}; Arai S et al.; Cefprozil (CFPZ, BMY-28100), a new oral cephem antibiotic, was studied for its antibacterial activities, absorption and excretion upon administration . Its clinical efficacies were also studied in pediatric patients with infections . A study on antibacterial activities of CFPZ against 11 clinical isolates including 6 species found that its activities against Staphylococcus aureus, alpha-hemolytic Streptococcus, Escherichia coli and Haemophilus influenzae were equal or superior to those of CCL . When CFPZ was given to patients orally at 15 mg/kg, maximum serum concentration was obtained between 1 to 2 hours after administration and urinary excretion rate in the first 6 hours was 33.8 +/- 17.6% . Clinical evaluation was done in a total of 25 patients with various infections . Responses were excellent in 15 cases and good in 10 cases, hence the efficacy rate was 100% . As side effect, soft stool was found in 1 case, and eosinophilia in 2 cases and elevation of GOT and GPT in 1 case were found as abnormal laboratory test results, but none of them was serious . It appears that CFPZ is an effective and safe antibiotic in the field of pediatrics. Jpn J Antibiot, 1992 Nov, 45(11), 1558 - 70 {Laboratory and clinical studies on cefprozil in the field of pediatrics}; Hayakawa F et al.; Laboratory and clinical studies on cefprozil (CFPZ, BMY-28100), a new cephem antibiotic, were carried out in the field of pediatrics . The results obtained are summarized as follows: 1 . Serum concentrations, urinary concentrations and urinary recovery rates of CFPZ were determined upon oral administration of CFPZ after meal at doses of 4 mg/kg granules in a case, 7.5 mg/kg granules in 2 cases and 15 mg/kg granules in one . Peak serum levels of CFPZ were obtained at an hour in 3 cases and at 2 hours in 1 case after administration of the drug with a range of 2.7-8.6 micrograms/ml with half-lives of 0.69-0.95 hours . Urinary recovery rates in the first 6 hours after administration ranged from 59.4-71.3% . 2 . MICs of CFPZ against 36 clinical isolates (Staphylococcus aureus 4 strains, Streptococcus pneumoniae 5, Streptococcus pyogenes 5, Escherichia coli 5, Haemophilus influenzae 12, Haemophilus parainfluenzae 4, and Branhamella catarrhalis 1) were compared with those of cefaclor (CCL) and ampicillin (ABPC) . The antibacterial activity of CFPZ was superior to those of CCL against Gram-positive cocci, and to those of ABPC against E . coli, and was equal to those of CCL and inferior to those of ABPC against H . influenzae . 3 . Thirty-seven pediatric patients with acute infectious diseases (pharyngitis/tonsillitis 17, bronchitis 7, pneumonia 3, skin and soft tissue infection 2, and urinary tract infection 8) were treated with CFPZ at daily doses of 10-47 mg/kg t.i.d . as a rule . The efficacy rates were 100% clinically and 56% bacteriologically . 4 . Side effects or abnormal laboratory test values were not observed except for an increased platelet count in 1 case and elevated GOT, GPT values in 2 cases. Jpn J Antibiot, 1992 Nov, 45(11), 1537 - 57 {Clinical study on cefprozil in pediatrics}; Iwai N et al.; Clinical efficacy and safety of cefprozil (CFPZ, BMY-28100), a newly developed oral cephalosporin, were studied in our pediatric department . Clinical effectiveness, bacteriological effectiveness and side effects were studied in 116 pediatric patients with ages ranging 4 months to 11 years . CFPZ was given 4.6-14.1 mg/kg daily in 3 times for 3-10 days . Clinical efficacies were evaluated in 112 patients, and the therapeutic effectiveness were excellent in 1 and good in 6 for 7 patients with acute pharyngitis, excellent in 24 and good in 26 for acute purulent tonsillitis, excellent in 3, good in 8 and fair in 1 for acute bronchitis, excellent in 21, good in 7, fair in 1 and poor in 1 for acute pneumonia, excellent in 1 acute purulent parotitis, excellent in 2 and good in 7 for acute UTI, good in 1 impetigo, fair in 1 periproctal abscess and good in 1 acute enteritis . The effectiveness rate was 96.4% . Bacteriologically, 4 strains of Staphylococcus aureus (beta-lactamase producing strains), 1 strain of Staphylococcus epidermidis (beta-lactamase producing strain), 2 strains of Streptococcus pneumoniae, 2 strains of Streptococcus agalactiae, 4 strains of beta-Streptococcus, 1 strain of Klebsiella pneumoniae (beta-lactamase producing strain) and 1 strain of Salmonella C2 were all disappeared, and of 22 strains of Streptococcus pyogenes, 20 strains were disappeared, 1 was decreased and 1 was unknown, of 5 strains of Escherichia coli (3 beta-lactamase producing strains), 4 were disappeared and 1 was decreased, of 29 strains of Haemophilus influenzae (14 beta-lactamase producing strains), 14 were disappeared, 11 were decreased, 3 persisted and 1 was unknown and of 2 strains of Haemophilus parainfluenzae (1 beta-lactamase producing strain), 1 was disappeared and 1 persisted . The bacteriological eradication rates for Gram-positive bacteria and Gram-negative bacteria were 97.1% and 56.8%, respectively, and the drug was especially effective against Gram-positive bacteria . No side effects nor refusal of ingestion were observed . As abnormalities in laboratory test results, 3 cases of elevation of eosinophil counts and 1 of elevation of platelet counts were observed . In conclusion, CFPZ was considered to be a safe and highly effective antibiotic in pediatric infections. Jpn J Antibiot, 1992 Nov, 45(11), 1505 - 13 {Clinical evaluation of a new oral cephem, cefprozil in children}; Meguro H et al.; Cefprozil (CFPZ, BMY-28100) was evaluated for its efficacy, safety and pharmacokinetics in children . CFPZ was effective against streptococcal pharyngitis, pneumococcal lower respiratory tract infections, staphylococcal skin infections and Escherichia coli urinary tract infections, but was less effective against lower respiratory tract infections and otitis media due to Haemophilus influenzae . No adverse reactions were encountered in 46 cases treated with CFPZ . With a premeal administration of 7.5 mg/kg, the Cmax was approximately 3.2 micrograms/ml and the T 1/2 beta was 1.4 hours . From the present study, CFPZ appears to be safe and effective against community-acquired childhood infections. Jpn J Antibiot, 1992 Nov, 45(11), 1451 - 9 {Antimicrobial activity of cefetamet against clinically isolated microbial strains collected from urban RTI patients}; Deguchi K et al.; The authors studied antimicrobial activities of cefetamet (CFMT) and other leading oral antimicrobials of beta-lactam class against clinically isolated strains from urban respiratory tract infection (RTI) patients from January to March, 1992 . 1 . CFMT showed potent antimicrobial activities against "3 primary pathogens" of RTIs i.e., Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae, but the drug had a slightly higher MIC than those of a few oxime-type cephems already on the market . 2 . CFMT was as stable as cefixime to beta-lactamase, generated by Moraxella subgenus Branhamella catarrhalis, which reduces the antimicrobial activity of cephems . 3 . Blood concentrations of CFMT after administering cefetamet pivoxil (CFMT-PI), an oral form of the drug, exceeded the MIC80 against the "3 primary pathogens" as well as M . (B) catarrhalis and Klebsiella pneumoniae, for a duration of approximately 9 and 11 hours, respectively, after single doses of 250 and 500 mg . This suggests that CFMT could remain above the MICs for a sufficient time period with twice daily dosages of normal dose levels . 4 . It is concluded that CFMT-PI will be useful for treating urban RTIs. Sex Transm Dis, 1992 Nov-Dec, 19(6), 309 - 14 Use of an adsorption enzyme immunoassay to evaluate the Haemophilus ducreyi specific and cross-reactive humoral immune response of humans; Alfa MJ et al.; Serodiagnosis of chancroid is limited by the cross-reactivity of Haemophilus ducreyi with Haemophilus influenzae and Haemophilus parainfluenzae . This research describes an adsorption enzyme immunoassay (EIA) that assesses the humoral immune response of North Americans and Africans to H . ducreyi . Adsorption effectively removed anti-H . influenzae and anti-H . parainfluenzae antibodies, revealing that North American control sera had no residual anti-H . ducreyi reactivity . However, African control sera still had a residual anti-H . ducreyi response . Assessment of the duration of the humoral immune response in sera from African patients with chancroid showed that the humoral antibodies persisted for up to 8 months after the diagnosis . This may explain the lack of specificity of the adsorption EIA in areas where chancroid is endemic . The detection of the humoral immune response was affected by the strain of H . ducreyi used, with indigent strains being most useful . Using H . ducreyi 35000 for Canadian sera, the sensitivity of the adsorption EIA was 100% and the specificity was 88% . For African sera, H . ducreyi strain R018 was used, and the adsorption EIA had a sensitivity of 81% and a specificity of only 23% . These data reveal that the existing humoral response in a country where chancroid is endemic differs from that in a country where it is not, and that care must be used interpreting unadsorbed humoral immune responses . The adsorption EIA approach may prove useful as an epidemiologic tool for definition of existing (past and present) levels of exposure to H . ducreyi. Antimicrob Agents Chemother, 1992 Nov, 36(11), 2569 - 72 Molecular basis of the efficacy of cefaclor against Haemophilus influenzae; Picard M et al.; Cefaclor sustained its inhibitory activity against a beta-lactamase-producing strain of Haemophilus influenzae . Although a relatively high permeability coefficient was calculated for ampicillin compared with that calculated for cefaclor, the resulting periplasmic concentration of cefaclor was 5.7 times that of ampicillin . The efficacy of cefaclor may be due to its higher beta-lactamase resistance, which allows it to achieve a greater periplasmic concentration and adequate binding to crucial penicillin-binding proteins. Diagn Microbiol Infect Dis, 1992 Nov-Dec, 15(8), 693 - 701 Haemophilus test medium interpretive criteria for disk diffusion susceptibility tests with cefdinir, cefetamet, cefmetazole, cefpodoxime, cefdaloxime (RU29246, HR-916 metabolite), and trospectomycin; Jones RN et al.; The disk diffusion zones and the MICs of six newer antimicrobials with significant activity against Haemophilus influenzae were compared using the Haemophilus test medium (HTM) and National Committee for Clinical Laboratory Standards methods . The rank order of potency was cefpodoxime (MIC50, < or = 0.03 micrograms/ml) > cefetamet > cefdinir > cefdaloxime = trospectomycin > cefmetazole (MIC50, 2 micrograms/ml) . Susceptible breakpoint interpretive criteria for HTM tests were established that conformed to prior recommendations for each drug when tested against other species . Absolute agreement between methods ranged from 89% to 100% with < or = 1% false-susceptible interpretive errors . The recommended, tentative disk diffusion susceptible interpretive criteria were for 5-micrograms cefdinir disks > or = 20 mm (MIC correlate, < or = 1 micrograms/ml); for 10-micrograms cefetamet disks > or = 18 mm (MIC correlate, < or = 4 micrograms/ml); for 30-micrograms cefetamet disks > or = 21 mm (MIC correlate, < or = 4 micrograms/ml); for 30-micrograms cefmetazole disks > or = 16 mm (MIC correlate, < or = 16 micrograms/ml); for 10-micrograms cefpodoxime disks > or = 21 mm (MIC correlate, < or = 2 micrograms/ml); for 30-micrograms cefdaloxime disks > or = 23 mm (MIC correlate, < or = 2 micrograms/ml) and for 30-micrograms trospectomycin disks > or = 17 mm (MIC correlate, < or = 16 micrograms/ml) . beta-Lactamase-negative, ampicillin-resistant (BLNAR) H . influenzae isolates consistently had the highest MICs for each cephalosporin tested.(ABSTRACT TRUNCATED AT 250 WORDS) Ann Pharmacother, 1992 Nov, 26(11), 1429 - 40 Haemophilus influenzae type B conjugate vaccines; Force RW et al.; OBJECTIVE: To review the epidemiology of Haemophilus influenzae type b (Hib) disease, the first Hib vaccine and its limitations, the characteristics and clinical efficacy of the newer conjugate vaccines, and the current recommendations for administration of Hib vaccines . DATA SOURCES: Pertinent literature was identified via a MEDLINE search . Additionally, references cited in published articles were used as data sources . STUDY SELECTION: Studies describing the epidemiology of Hib disease and the efficacy and/or immunogenicity of the Hib vaccines are reviewed . DATA SYNTHESIS: Serious invasive disease secondary to Hib infection causes significant morbidity and mortality in children between the ages of three months and five years . The original Hib vaccine was found to be ineffective in stimulating an adequate immune response in children younger than two years of age . The new Hib conjugate vaccines provide superior efficacy and immunogenicity compared with the original unconjugated vaccine . They stimulate an immune response that is distinctly different from that elicited by the original vaccine . Two vaccine products are currently licensed for use in children as young as two months of age, thus conferring immunity to those children at highest risk for Hib disease . CONCLUSIONS: The new Hib conjugate vaccines provide excellent efficacy and, when used as recommended, may significantly reduce the incidence of invasive Hib disease and its sequelae. Clin Infect Dis, 1992 Nov, 15 Suppl 1, S162 - 6 Evaluation of new anti-infective drugs for the treatment of acute hematogenous osteomyelitis in children . Infectious Diseases Society of America and the Food and Drug Administration; Nelson JD et al.; Most children with acute hematogenous osteomyelitis have no preceding illness . Their early symptoms are pain and fever . A bacterial etiology is established in approximately 75% of cases by needle aspiration of the affected site or blood culture . Clinical trials should be limited to cases of bacterial origin . The antimicrobial agents studied should be active against Staphylococcus aureus and streptococci . If children < 5 years of age are included, the drug should also be active against beta-lactamase-negative and -positive strains of Haemophilus influenzae . Randomized, prospective, double-blind comparative studies are preferable to open, evaluator-blinded trials . Clinical outcome is appraised by physical signs and symptoms . A successful microbiological outcome consists of presumptive eradication . The final assessment should be made 1 year after completion of therapy. Clin Infect Dis, 1992 Nov, 15 Suppl 1, S108 - 14 Evaluation of new anti-infective drugs for the treatment of chancroid . Infectious Diseases Society of America and the Food and Drug Administration; Ronald AR et al.; Chancroid is a mucocutaneous infection caused by Haemophilus ducreyi that produces ulcerative lesions and enhances the efficiency of transmission of human immunodeficiency virus (HIV) . Confirmation of infection by culture of H . ducreyi is essential in therapeutic trials . Minimal inhibitory concentrations of antibiotics for the isolate should be determined by agar dilution . Patients should be evaluated by appropriate laboratory tests for syphilis, infection with herpes simplex virus, gonorrhea, and (in North America) infection with Chlamydia trachomatis . The clinical history of the disease should be recorded and ulcers, buboes, and lymphadenitis mass described . Whenever possible, study participants also should be tested for HIV infection . Randomized, prospective, double-blind, active-control comparative clinical trials are preferred for evaluation of the safety and efficacy of new anti-infective drugs . Otherwise-healthy men and women should be enrolled in these studies . Patients with active syphilis or genital herpes should be excluded . Microbiological and clinical outcomes are paramount. Acta Paediatr, 1992 Nov, 81(11), 941 - 3 Chloramphenicol-resistant Haemophilus influenzae meningitis in young urban Nigerian children; Johnson AW et al.; In a developing country like Nigeria, the unusual emergence of Haemophilus influenzae type b, resistant to cost-effective antimicrobials, is of serious concern . We report three cases of H . influenzae type b meningitis in young Nigerian children in whom clinical and bacteriological features of resistance to chloramphenicol were identified . One of the cases had concomitant resistance to ampicillin (multiple-drug resistance) . Significant anaemia was an associated feature in two cases, one of whom had a recent measles infection . All three cases were malnourished . The possible mechanisms of antimicrobial resistance in H . influenzae infections are highlighted while the need for periodic surveillance of antibiotic resistance profiles in resource-poor countries is emphasized . The potential value of prophylactic measures like H . influenzae type b conjugate immunization is discussed. Arch Intern Med, 1992 Nov, 152(11), 2301 - 4 Purulent otitis media in adults; Schwartz LE et al.; While the bacterial origin of otitis media has been studied extensively in children, there are few data regarding adults with this disease . We undertook this study to identify the incidence, prevalence, and bacteriologic origin of purulent otitis media in adults . This was accomplished through a review of the English-language literature on adult otitis media and a retrospective review of adult patients with this disease who were hospitalized at our institution . Results of literature review indicate that Streptococcus pneumoniae and Haemophilus influenzae are the most common causes of otitis media in ambulatory adults, but this illness is uncommon, with an incidence of only 0.25% . Hospitalized patients in whom this diagnosis was established suffered a variety of serious suppurative complications such as mastoiditis, meningitis, or brain abscess . Otalgia and fever were the most common symptoms noted in this patient population . Further studies of adult otitis media need to be performed to determine bacteriologic, symptomatic, and high-risk patient groups. Arch Intern Med, 1992 Nov, 152(11), 2277 - 82 High incidence rates of invasive pneumococcal disease in the White Mountain Apache population; Cortese MM et al.; OBJECTIVE--In this article we determine the incidence and clinical spectrum of invasive pneumococcal disease in the White Mountain Apache population, a group known to have a high incidence of invasive disease due to Haemophilus influenzae type b . DESIGN--Patients from whom cultures of normally sterile body sites yielded Streptococcus pneumoniae were identified retrospectively through review of hospital laboratory records from a 6.8-year period . Clinical data were reviewed and incidence rates were computed . SETTING--The Whiteriver Indian Health Service Hospital is located on the 1.7-million-acre White Mountain Apache Reservation in eastern Arizona . PATIENTS--Approximately 10,000 members of the White Mountain Apache Tribe reside on or near the reservation and receive health care through the Whiteriver Indian Health Service Hospital . OUTCOME MEASURES--The average annual incidence rates of invasive pneumococcal disease were calculated and clinical characteristics were reviewed . RESULTS--One hundred thirty-eight cases of invasive pneumococcal disease were identified . The average annual incidence rate was 207 per 100,000 population, and 156 per 100,000 population when adjusted for age by direct standardization to the 1988 US population . The incidence rate was highest in children between 1 and 2 years--2396 per 100,000 . The overall case-fatality rate was 5% . Pneumococcal pneumonia was the diagnosis in 79% of the patients 5 years of age or older . Alcohol abuse, identified in 66% of the cases in adults, was the most common underlying medical condition . CONCLUSION--The incidence rates in White Mountain Apaches are the highest reported for any population . A vaccine effective in children would greatly benefit this population. Proc Natl Acad Sci U S A, 1992 Nov 1, 89(21), 10252 - 6 A periplasmic protein disulfide oxidoreductase is required for transformation of Haemophilus influenzae Rd; Tomb JF; The mutated gene in JG16, a Haemophilus influenzae strain deficient in competence-induced DNA binding and uptake, was cloned and the wild-type allele was sequenced . The gene was shown by Northern analysis to be constitutively expressed on a 1.7-kilobase transcript . The gene product was identified as a 20.6-kDa protein targeted to the periplasm . The protein contains the sequence Cys-Pro-His-Cys (CPHC) and is highly similar to two other periplasmic CPHC motif-containing proteins: DsbA, an Escherichia coli protein (45% identity, 87% homology) and TcpG, a Vibrio cholerae protein (32% identity, 74% homology) . Both DsbA and TcpG promote disulfide bond formation in periplasmic proteins, are required for pilus biogenesis, and, like thioredoxin, are capable of reducing insulin in vitro . The Haemophilus protein was shown to complement an E . coli mutation in DsbA and was named Por (periplasmic oxidoreductase) . In JG16 the competence-dependent redistribution of inner membrane proteins did not occur . These findings suggest that Por is required for the correct assembly and/or folding of one or more disulfide-containing cell envelope protein involved either in competence development or in the DNA-binding and -uptake machinery. J Bacteriol, 1992 Nov, 174(22), 7245 - 52 Use of chromosomal gene fusions to investigate the role of repetitive DNA in regulation of genes involved in lipopolysaccharide biosynthesis in Haemophilus influenzae; Szabo M et al.; The lic3 locus of Haemophilus influenzae consists of four open reading frames . The derived amino acid sequences of orf2 and orf4 exhibit homology to Escherichia coli GalE and AdK, respectively . The functions of orf1 and orf3 remain unknown . orf1 contains multiple tandem repeats of the tetrameric DNA sequence CAAT near the 5' end . Two possible translational starts (ATG1 and ATG2) lie upstream . We have used lacZ fusions to investigate whether changes in the number of CAAT repeats in conjunction with differential usage of the upstream frames control the expression of lic3-orf1 . Phase-variable expression of lacZ was observed for individual colonies and could be related to variable numbers of CAAT repeats . Of the three possible upstream frames, only one, containing the more downstream of the two possible ATG start codons (ATG2), is used for strong expression of lacZ . Utilization of the more upstream ATG (ATG1) or ATG2 was observed with medium-level expression, while utilization of any of the three possible frames was observed when lacZ was expressed at low to undetectable levels, indicating that other mechanisms may affect expression . To investigate this, lacZ was fused in frame with ATG2 of lic3-orf1, with concomitant deletion of the repeats . Phase-variable expression was still observed, supporting the view that an alternative level of control operates in conjunction with the repeat mechanism. Chest, 1992 Nov, 102(5), 1562 - 5 Pneumonia due to Haemophilus influenzae among mechanically ventilated patients . Incidence, outcome, and risk factors; Rello J et al.; Incidence and potential risk factors for pneumonia due to Haemophilus influenzae in adults treated with mechanical ventilation in a medical-surgical ICU were investigated . Diagnosis was established in 91 episodes and H influenzae was isolated in 20 of them . Mean onset of ventilator-associated pneumonia (VAP) due to H influenzae was 10.8 days after intubation . Six patients with H influenzae VAP died in the ICU . Of 13 risk factors for developing VAP due to H influenzae, an absence of prior antibiotic treatment was the only variable which had statistical significance (p < 0.001) . In these mechanically ventilated patients, Haemophilus influenzae was a common causative agent for VAP, frequently associated with Gram-positive cocci . Episodes of H influenzae VAP were associated with a lower mortality compared with other etiologies . The epidemiologic and clinical findings indicate that patients without a prior antimicrobial treatment have increased susceptibility to infections of the airway by H influenzae. Clin Exp Immunol, 1992 Nov, 90(2), 223 - 7 Cellular changes in the bronchoalveolar lavage (BAL) of pigs, following immunization by the enteral or respiratory route; Delventhal S et al.; Normal young pigs were immunized by the oral or aerogenic route with the viable or inactivated lung-pathogenic bacterium Actinobacillus (Haemophilus) pleuropneumoniae . Three weeks later the cellular composition as well as the lymphocyte subset composition of the bronchoalveolar space were examined by BAL . Lymphocytes in the lavage increased significantly, including CD4+ and CD8+ T cells . After oral immunization a dramatic increase of plasma cells and lymphoid blasts was found . Among immunoglobulin-positive lymphocytes IgG+ cells showed the most pronounced increase . For most lymphocyte subsets there was no difference between viable and inactivated bacteria . Oral immunization with a lung-pathogenic bacterium results in increased numbers of lymphocytes in the bronchoalveolar space and might play a critical role in protection against lower respiratory tract infections. Arch Otolaryngol Head Neck Surg, 1992 Nov, 118(11), 1229 - 31 Bacteremia during tonsillectomy; Francois M et al.; To determine the risk of bacteremia during tonsillectomy, we cultured blood specimens that were taken from 32 children during surgery and tonsillar swabs that were obtained just before excision, and compared the results with quantitative cultures of the excised tonsillar tissue . Twenty-five children had Haemophilus influenzae within the tonsillar tissue (density range, 10(3) to 10(8) colony-forming units per gram), and seven had Streptococcus pyogenes (density, 10(3) colony-forming units per gram in one case, 10(5) colony-forming units per gram in one case, and 10(6) colony-forming units per gram in five cases) . Twelve perioperative blood cultures were positive; H influenzae was found nine times, and Micrococcus species was found one time, and alpha-hemolytic streptococci were found two times . Haemophilus influenzae was always present in the corresponding tonsillar specimens, although there was no apparent relationship between the density of colonization of the tonsillar tissue and a positive blood culture. J Infect Dis, 1992 Nov, 166(5), 1021 - 8 Immunogenicity of Haemophilus influenzae type b conjugate vaccine in allogeneic bone marrow recipients; Barra A et al.; A randomized study was conducted in 40 allogeneic marrow recipients to compare the immunogenicity of two Haemophilus influenzae type b (Hib) vaccines (either the Hib capsular polysaccharide {Hib-CPS} or tetanus toxoid-conjugated Hib-CPS {Hib-CPS-T}) . A second injection consisted of Hib-CPS-T . Before immunization, 3 patients had serum antibody levels > 1 microgram/mL . After the first injection, the response was better after Hib-CPS-T than after Hib-CPS but lower than in normal subjects; a number of patients lacked any IgG antibody response, especially after Hib-CPS . Of patients who received two injections of Hib-CPS-T, 85% achieved an antibody concentration > or = 1 microgram/mL . Hib-CPS-T induced a response in IgG2-deficient patients whereas Hib-CPS alone did not . IgG antibodies predominantly belonged to the IgG1 subclass . The antibody response was better in patients immunized late after graft . This study shows that Hib-CPS-T is more immunogenic than Hib-CPS in marrow recipients. Infect Immun, 1992 Nov, 60(11), 4838 - 47 Complement activation by polyclonal immunoglobulin G1 and G2 antibodies against Staphylococcus aureus, Haemophilus influenzae type b, and tetanus toxoid; Bredius RG et al.; To obtain information on effector functions of human immunoglobulin G2 (IgG2), we have measured the complement-activating properties of polyclonal IgG subclass antibodies against bacterial antigens . IgG1 and IgG2 were purified from serum samples from five healthy individuals, and complement activation was measured with different bacterial antigens . We used Staphylococcus aureus Wood 46 (STAW), which is a common antigen, Haemophilus influenzae type b (Hib), which is a common pathogenic microorganism in children, and formaldehyde-inactivated tetanus toxin (TT) . Bacteria were incubated with antibodies and then incubated with sera from agammaglobulinemic patients as a complement source, and C3c deposition was measured by enzyme-linked immunosorbent assay . We found that anti-STAW IgG2 activated complement to a level similar to that of anti-STAW IgG1 . Anti-Hib IgG1 complement activation was as much as seven times higher than that of anti-Hib IgG2 in four individuals . In one individual, anti-Hib IgG2 was more effective in complement activation than anti-Hib IgG1 . Anti-TT antibodies showed patterns similar to those of anti-Hib . Our results indicate that IgG2 antibodies may contribute significantly to antibacterial defense . Also, individual differences in antibody effector functions should be taken into account when evaluating the immune status of patients and during early phase 1 studies of new vaccines. J Hosp Infect, 1992 Nov, 22 Suppl A, 89 - 97 In-vitro bactericidal activity of four oral antibiotics against pathogens responsible for acute otitis media in children; Lambert-Zechovsky N et al.; This study was designed to test the in-vitro activity of four oral antibiotics against the four microorganisms most frequently isolated in acute otitis media: beta-lactamase-positive Haemophilus influenzae (N = 10), beta-lactamase-positive Moraxella catarrhalis (N = 10), penicillin-sensitive Streptococcus pneumoniae (N = 11) and methicillin-sensitive Staphylococcus aureus (N = 10), by the bactericidal curve method . Bactericidal kinetics were determined for concentrations of antibiotic equivalent to those found in the middle ear after treatment: amoxycillin-clavulanic acid (2.5 mg l-1/0.6 mg l-1 and 2.5 mg l-1/1.2 mg l-1), cefaclor (1 mg l-1), erythromycin (0.5 mg l-1) and erythromycin/sulfisoxazole (0.2/3 mg l-1) . The inoculum was of 10(6) colony-forming units (cfu) ml-1 . The bacterial counts were performed after 5 h and 24 h using a spiral inoculator system . The results showed that amoxycillin-clavulanic acid had rapid bactericidal activity (< 24 h) on the tested organisms at each of the doses used (reduction < or = 3 log10 cfu ml-1) which was not observed with the other antibiotics at either 5 or 24 h . Erythromycin alone or combined with sulfisoxazole had a bacteriostatic effect on Moraxella catarrhalis and Streptococcus pneumoniae but not on Haemophilus influenzae or Staphylococcus aureus . Cefaclor had no bactericidal action under these conditions. Indian J Pediatr, 1992 Nov-Dec, 59(6), 719 - 21 Bacterial meningitis in Saudi children; Srair HA et al.; During the four years period from 1988 to 1991, 50 pediatric patients were diagnosed to have bacterial meningitis, out of a total number of 9057 pediatric admissions at Qatif Central Hospital, Qatif, Saudi Arabia, and 82% were less than two years of age . The causative organisms were isolated in 27 (54%) patients . The bacteria grown included Haemophilus influenzae type B in 8 patients (29.6%), Neisseria meningitidis in 8 patients (29.6%), Streptococcus pneumonia in 6 (22%) patients, and other bacteria in 5 patients (18.5%) . Cerebro spinal fluid cultures from twenty three patients (46%) showed no organisms, however their clinical and C.S.F . findings were compatible with bacterial meningitis . One case of H . influenzae type B was resistant to ampicillin . Six patients died with an over all mortality of 12%, and 10 patients (20%) developed some kind of C.N.S . sequelae . Partially treated meningitis formed a large percentage of our sample. J Clin Microbiol, 1992 Nov, 30(11), 3013 - 5 Interpretive criteria and quality control parameters for testing susceptibility of Haemophilus influenzae to enoxacin, ofloxacin, and temafloxacin; Barry AL et al.; Haemophilus influenzae isolates were uniformly susceptible to enoxacin, ofloxacin, and temafloxacin . Zone diameter and MIC interpretive criteria were proposed to define susceptible populations so that mutants with diminished susceptibility might be detected when and if they appear in clinical specimens . Additional collaborative quality control studies defined MIC and zone size limits for tests with H . influenzae ATCC 49247. Kansenshogaku Zasshi, 1992 Nov, 66(11), 1502 - 12 {Identification of strains on recurrent Haemophilus influenzae infections in patients with chronic respiratory tract infections}; Takahashi A; Nontypable Haemophilus influenzae is one of the most important pathogenic bacteria in respiratory tract infections . H . influenzae is most frequently associated with recurrent infections in chronic respiratory tract infections (CRTIs) . It is known that H . influenzae often reemerges after the antibiotic treatment has been stopped . We analyzed serotype, biotype, and the OMP patterns of H . influenzae isolates from sputum of CRTIs patients to determine whether an exacerbation is caused by an identical H . influenzae strain, or by a new H . influenzae strain . One hundred eighty nine strains of H . influenzae were obtained from 124 exacerbation from 24 patients . The first and second isolates were identical in 23 out of 33 exacerbations (< or = 15-days interval between each exacerbation) and also in 22 out of 34 exacerbations (15 < days but < or = 30-days interval between each exacerbation) . This is called early recurrence . In contrast, the first and second isolates were different in 28 out of 34 exacerbations (> 30-days interval between each exacerbation) . This is called late recurrence . These results suggest that early recurrence and late recurrence of recurrent H . influenzae infections occur in a different mechanism. Drugs, 1992 Nov, 44(5), 750 - 99 Azithromycin . A review of its antimicrobial activity, pharmacokinetic properties and clinical efficacy; Peters DH et al.; Azithromycin is an acid stable orally administered macrolide antimicrobial drug, structurally related to erythromycin, with a similar spectrum of antimicrobial activity . Azithromycin is marginally less active than erythromycin in vitro against Gram-positive organisms, although this is of doubtful clinical significance as susceptibility concentrations fall within the range of achievable tissue azithromycin concentrations . In contrast, azithromycin appears to be more active than erythromycin against many Gram-negative pathogens and several other pathogens, notably Haemophilus influenzae, H . parainfluenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Urea-plasma urealyticum and Borrelia burgdorferi . Like erythromycin and other macrolides, the activity of azithromycin is unaffected by the production of beta-lactamase . However, erythromycin-resistant organisms are also resistant to azithromycin . Following oral administration, serum concentrations of azithromycin are lower than those of erythromycin, but this reflects the rapid and extensive movement of the drug from the circulation into intracellular compartments resulting in tissue concentrations exceeding those commonly seen with erythromycin . Azithromycin is subsequently slowly released, reflecting its long terminal phase elimination half-life relative to that of erythromycin . These factors allow for a single dose or single daily dose regimen in most infections, with the potential for increased compliance among outpatients where a more frequent antimicrobial regimen might traditionally be indicated . The potential disadvantage of low azithromycin serum concentrations, however, is that breakthrough bacteraemia may occur in patients who are severely ill; nevertheless, animal studies suggest that tissue concentrations of azithromycin are more important than those in serum when treating respiratory and other infections . The clinical efficacy of azithromycin has been confirmed in the treatment of infections of the lower and upper respiratory tracts (the latter including paediatric patients), skin and soft tissues (again including paediatric patients), in uncomplicated urethritis/cervicitis associated with N . gonorrhoeae, Chlamydia trachomatis or U . urealyticum and in the treatment of early Lyme disease . Azithromycin was as effective as erythromycin and other commonly used drugs including clarithromycin, beta-lactams (penicillins and cephalosporins), and quinolone and tetracycline antibiotics in some of the above infections . Some patients with acute exacerbations of chronic bronchitis due to H . influenzae may be refractory to therapy with azithromycin (as is the case with erythromycin) indicating the need for physician vigilance, although it should be noted that azithromycin is of equivalent efficacy to amoxicillin in the treatment of such patients . In the therapy of urethritis/cervicitis associated with C . trachomatis, N . gonorrhoea or U . urealyticum, a single dose azithromycin regimen offers a distinct advantage over currently available pharmacological options, while providing effective therapy.(ABSTRACT TRUNCATED AT 400 WORDS) Med J Aust, 1992 Oct 19, 157(8), 519 - 20 Outcome of paediatric bacterial meningitis 1979-1989; Thomas DG; OBJECTIVE: To determine the outcome of all cases of paediatric bacterial meningitis over the 11-year period 1979-1989 and discuss the role of adjunctive therapy with dexamethasone . DESIGN AND SETTING: The study was performed by retrospective case review at Flinders Medical Centre, a general teaching hospital . RESULTS: There were 80 episodes in 79 patients . The age range was 2 days to 15 years (mean, 1.7 years) . Haemophilus influenzae type b was the commonest organism (60 of 80 cases; 75%) . There were five deaths (6.3%) . Sensorineural hearing loss was found in six of 71 children (8.5%) and was bilateral and severe in four (5.6%) . Other problems included learning difficulties (12.7%), motor problems (7%), speech delay (7%), hyperactivity (4.2%), blindness (2.8%), obstructive hydrocephalus (2.8%) and recurrent seizures (2.8%) . CONCLUSIONS: Bacterial meningitis remains a disease with significant morbidity and mortality . Adjunctive therapy with dexamethasone should be considered, and vaccination against Haemophilus influenzae type b should be routine. Arch Ophthalmol, 1992 Oct, 110(10), 1450 - 4 Endophthalmitis caused by gram-negative organisms; Irvine WD et al.; The medical records of 52 patients (53 eyes) with culture-proven gram-negative endophthalmitis between January 1982 and December 1990 were reviewed . Pseudomonas aeruginosa (23% {12/53}) and Haemophilus influenzae (19% {10/53}) were the most frequent isolates in this series . Overall, 26 (49%) of 53 treated patients achieved 20/400 or better visual acuity . Fifty-two (98%) of the original 53 gram-negative isolates were sensitive to the aminoglycoside antibiotics . To determine their sensitivity to recently developed antibiotics, 35 of the isolates were again grown on culture media and their sensitivities to ceftazidime, ciprofloxacin, and imipenem were obtained . Only ceftazidime demonstrated in vitro efficacy for all the organisms tested. Protein Sci, 1992 Oct, 1(10), 1326 - 32 A new subfamily of bacterial ABC-type transport systems catalyzing export of drugs and carbohydrates; Reizer J et al.; Sequence comparison studies revealed that the drug resistance transporter of Streptomyces peucetius (DrrAB) and two nodulation gene products (NodIJ) of Rhizobium leguminosarum are homologous to proteins encoded by three sets of genes that comprise capsular polysaccharide export systems in gram-negative bacteria: KpsTM of Escherichia coli, BexABC of Haemophilus influenzae, and CtrDCB of Neisseria meningitidis . These five systems comprise a new subfamily within the family of ATP binding cassette (ABC)-type transporters . We have termed this subfamily the ABC-2 subfamily . For three of the systems comprising this subfamily (Drr, Nod, and Kps) only one integral membrane constituent has been identified, whereas for the other two systems (Bex and Ctr) two dis-similar integral membrane constituents have been found . This observation suggests that the transmembrane channels of ABC-2-type transporters can be formed of homo- or heterooligomers as is true of several other classes of transport systems. Eur J Clin Microbiol Infect Dis, 1992 Oct, 11(10), 930 - 4 A simple medium for the primary isolation of Haemophilus ducreyi; Dangor Y et al.; Two simple, inexpensive media containing gonococcal agar-base, supplemented with 5% Fildes' extract and either chocolated or unchocolated horse blood (GC-FHBC or GC-FHB) were compared with the standard gonococcal agar-based (GC-HgS) and Mueller-Hinton agar-based media (MH-HB) normally used for primary isolation of Haemophilus ducreyi from presumptive chancroid lesions . Overall, Haemophilus ducreyi was recovered from 162 of 178 (91%) samples from primary chancroid lesions . As a single isolation medium GC-HgS proved the most sensitive with an isolation rate of 80% followed by GC-FHB (75%), MH-HB and GC-FHC (both 71%) . Use of a combination of GC-HgS and MH-HB resulted in isolation of Haemophilus ducreyi in 160 of 178 cases (90%) . Since GC-FHB is approximately one-quarter the cost of the combination and half the cost of GC-HgS or MH-HB alone, this medium could prove suitable for diagnostic purposes in developing countries where chancroid is endemic. Thorax, 1992 Oct, 47(10), 818 - 20 Microbial flora of the trachea during intubation of patients undergoing upper abdominal surgery; Dilworth JP et al.; BACKGROUND: The presence of Haemophilus influenzae in the oropharynx is correlated with the subsequent development of chest infection . The importance of colonisation of the trachea by bacteria at the time of surgery is uncertain . This study investigated the tracheal flora at the time of intubation in 24 patients undergoing elective upper abdominal surgery . METHODS: The bacterial flora of the trachea was sampled in all 24 patients immediately after intubation and immediately before extubation . Patients were assessed postoperatively for the development of chest infection . RESULTS: Bacteria, including H influenzae in five cases, were isolated from the post-intubation brushings of the trachea of 15 patients . The pre-extubation brushings from only four patients yielded growth . Three of five patients developing a chest infection were colonised by H influenzae according to the postintubation brush, compared with two of 19 without chest infections . Before extubation two of five developing chest infections had H influenzae in the trachea but none of 19 without infection . All but one of the patients from whom H influenzae was isolated were smokers . CONCLUSIONS: These results suggest that the increased risk of postoperative chest infection in cigarette smokers may be due in part to colonisation of the trachea by H influenzae at the time of operation. Jpn J Antibiot, 1992 Oct, 45(10), 1403 - 19 {Laboratory and clinical evaluation of meropenem in pediatric field}; Iwai N et al.; We performed laboratory and clinical evaluation of meropenem (SM-7338, MEPM), a new carbapenem antibiotics, in pediatric field . Pharmacokinetics of MEPM was examined with 5 patients, at a dose of 10 mg/kg via 30 minutes drip infusion . Mean plasma concentrations at 30 minutes, 1, 1.5, 2.5, 3.5 and 5.5 hours after dose were 18.8, 6.97, 3.62, 1.14, 0.43 and 0.12 micrograms/ml, respectively, with a half life of 0.96 hour . The urine recovery rate in 6 hours was 70.4% . Clinical efficacy of MEPM was evaluated in 36 patients with various infectious diseases . MEPM was administered at doses ranging 9.5 to 30.6 mg/kg/dosage, 3 to 4 times a day, 21/3 to 10 days . Clinical effects were excellent in 24, good in 11, fair in 1, with an efficacy rate of 97.2% . Bacteriologically, all causative organisms except one each of Haemophilus influenzae and Salmonella enteritidis were eradicated, an eradication rate for Gram-positive and Gram-negative bacteria were 100% and 93.3%, respectively . No side effects were observed . Elevations of GOT and/or GPT were noted in 2 patients . From the above results, we believe that MEPM is a highly effective and safe drug for patients with various infectious diseases in pediatric fields. Ann Pediatr (Paris), 1992 Oct, 39(8), 485 - 90 {Bacterial epidemiology of acute otitis media}; Gehanno P et al.; Since the middle of the 1980's, Haemophilus influenzae is the most common bacterial species responsible for acute otitis media in France, followed by Streptococcus pneumoniae . Haemophilus influenzae has maintained its leading position since 1985, but the rate of pneumococcal acute otitis media is increasing fairly steadily . The other recent change with regard to the distribution of bacterial agents is the emergence, four years later than in North America, of Branhamella catarrhalis which currently accounts for 10% of cases of acute otitis media . Modifications in the behavior of microorganisms in relation to antimicrobials usually given to treat upper respiratory tract infections have occurred . Staphylococcus aureus and Branhamella catarrhalis have always exhibited marked resistance to ampicillin due to the production of beta-lactamases . Resistance of Haemophilus influenzae to ampicillin has been increasing gradually since 1985, again with a lag of a few years as compared with the United States; at present, this form of resistance is seen in approximately 35% of strains . More recently in France, 20% of pneumococcal strains recovered from middle ear pus have been shown to have abnormal susceptibility to penicillin . These changes in the behavior of the two main pathogens, i.e., Haemophilus influenzae and Streptococcus pneumoniae, require implementation of rigorous multiregional epidemiologic surveillance programs and may justify reappraisal of current therapeutic approaches. Vet Microbiol, 1992 Oct, 32(3-4), 319 - 25 Sequence analysis of the ROB-1 beta-lactamase gene from Actinobacillus pleuropneumoniae; Chang YF et al.; The ROB-1 beta-lactamase gene from Actinobacillus pleuropneumoniae was cloned and sequenced . The structural gene encodes a 305 amino acid polypeptide . The ROB-1 beta-lactamase gene sequence is identical to that derived from Pasteurella haemolytica and only one amino acid different from that of Haemophilus influenzae, suggesting that they are derived from the same ancestor, and transformed from one to another. Gesundheitswesen, 1992 Oct, 54(10), 528 - 34 {Vaccination against Haemophilus influenzae B and rubella}; Windorfer A; Haemophilus influenzae B was the most frequent pathogen of bacterial meningitis in childhood during the mid-eighties to the end of the eighties of the present century, taking the place of meningococci since approximately 1984 at about twice the rate of that pathogen, as shown by the records kept during 1980-1990 in Bavarian Departments of Paediatrics . In fact, in 1990 the incidence of HIB meningitides was about 2.5 times that of meningococcus meningitides (85 vs . 34, respectively) . For practically 2 years now vaccination against HIB is being publicly recommended and should be made use of as intensively as possible to prevent all HIB infections . For several years the principle of on-target rubella vaccination has been applied to schoolgirls in Lower Saxony, Bremen and Hamburg to prevent rubella embryopathy, a procedure that has proved much more successful than blank vaccination . None of the other Federal German Laender have been following this procedure to date; in consequence there of, although the strategy of on-target vaccination will be continued in Lower Saxony, greater uniformity and greater efficiency are being aimed at throughout Germany by public recommendation of rubella vaccination at an infant age. Gut, 1992 Oct, 33(10), 1331 - 7 Fasting hypochlorhydria with gram positive gastric flora is highly prevalent in healthy old people; Husebye E et al.; Fifteen healthy old people mean age 84 years (range 80-91 years), were examined to assess the effect of advanced age on the microecology of the upper gastrointestinal tract . Twelve of 15 (80%) were hypochlorhydric with pH 6.6 (0.3) (mean (SEM) and a mean bacterial count of 10(8) colony forming units (CFU) per ml (range 10(5)-10(10)) in fasting gastric aspirate . Normochlorhydric subjects had low counts (< or = 10(1) CFU/ml) . The microbial flora was dominated by viridans streptococci, coagulase negative staphylococci, and Haemophilus sp . Only one subject harboured significant concentrations of Gram negative bacilli with Escherichia coli (10(4-5) CFU/ml) and Klebsiella (10(4-5)) . Strict anaerobes were not found . The total concentration of short chain fatty acids in gastric aspirate was 10.6 (2.9) mmol/l (mean (SEM) . Absence of significant, intraluminal fermentation of xylose to CO2 was shown by the 14C-d Xylose breath test, and ambulatory manometry showed preserved fasting motility pattern of the small intestine . Serum immunoglobulins were normal . Advanced age is accompanied by fasting hypochlorhydria and colonisation with mainly Gram positive flora in the upper gut . Other factors than old age and fasting hypochlorhydria are required for colonisation with Gram negative bacilli. Antimicrob Agents Chemother, 1992 Oct, 36(10), 2147 - 55 Effect of beta-lactams on peptidoglycan metabolism of Haemophilus influenzae grown in animals; Rousseau N et al.; We have examined bacterial determinants that influence beta-lactam activity in Haemophilus influenzae cells cultivated in a system that reproduces in vivo growth conditions . Bacteria grown in diffusion chambers were recovered from the peritoneal cavities of rats, and their cell properties were compared with those of bacteria grown in broth cultures by various tests performed in vitro . The rate of peptidoglycan synthesis was measured as the incorporation of {14C}alanine into cell wall material in the presence of chloramphenicol . The total incorporation of {14C}alanine into peptidoglycan was markedly increased in cells grown in rats prior to the assay but was efficiently reduced by the beta-lactams . The extent of cross-linking was lower in the peptidoglycan of in vivo-grown bacteria, as estimated by sodium dodecyl sulfate- to trichloroacetic acid-insoluble radioactive cell wall material ratios . A whole-cell labeling assay with 125I-penicillin was used to characterize the penicillin-binding proteins (PBPs) . Four PBPs showed a striking reduction in the binding of the labeled penicillin in cells grown in rats . Such changes resembled the PBP alterations seen in beta-lactamase-negative clinical strains that were resistant to the beta-lactams . Although ampicillin and moxalactam showed delayed inhibitory activities in vitro for cells collected from rats, cells recovered from beta-lactam-treated rats showed evidence of antibiotic effectiveness (binding of the beta-lactams to PBPs in vivo and altered morphology), and the killing of cells exposed to antibiotics in broth or in peritoneal fluid was equally good . Finally, the frequencies of spontaneous resistance or tolerance to ampicillin or moxalactam were estimated, and there was no significant difference for in vitro- or in vivo-grown cells . These data demonstrated that the cultivation of H . influenzae in animals created changes in PBPs and the overall peptidoglycan metabolism . Such alterations did not impair the bactericidal activities of the beta-lactams, although they resulted in delayed bacterial inhibition, a phenomenon that may have important consequences in antibiotherapy. Eur J Pediatr, 1992 Oct, 151(10), 779 - 82 Cortical visual impairment following bacterial meningitis: magnetic resonance imaging and visual evoked potentials findings in two cases; Thun-Hohenstein L et al.; Cortical visual impairment (CVI) following bacterial meningitis is a very uncommon complication . Two children with CVI following bacterial meningitis are reported . Bacterial agents were Haemophilus influenzae type B in one and meningococci in the other child . Both children showed only insufficient recovery from CVI, mental retardation and residual neurological symptoms . Flash visual evoked potentials (VEP) showed preserved cortical response at onset of CVI . Re-evaluations several months later showed significantly reduced amplitudes, but normal latencies for P100 . Thus, flash VEP does not allow prediction of visual outcome . MRI results have not been reported before . MRI at onset of diagnosis showed occipital parenchymal irregularities with enlarged sulci and subarachnoid spaces . Follow up MRI 15 months after onset of CVI in one patient showed marked atrophy of the occipital cortex, hyperintensities of the cortical white matter and no visible optic radiation . The MRI findings indicate hypoxic-ischaemic lesions in the border zone between the distribution of the great cerebral arteries. Clin Infect Dis, 1992 Oct, 15(4), 720 - 5 A two-year prospective, nationwide study to determine the epidemiology and impact of invasive childhood Haemophilus influenzae type b infection in Israel . The Israeli Pediatric Bacteremia and Meningitis Group; Dagan R; Accurate data on invasive Haemophilus influenzae type b (Hib) disease from countries other than the United States and western Europe are limited, and none are available from the Middle East . We report the results 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 2 study years, 344 patients less than 13 years of age with a positive blood or CSF culture for Hib were seen in 25 medical centers in which pediatric patients were hospitalized . The overall incidence of Hib disease was 34 per 100,000 persons less than 5 years old, an incidence in the range of those reported for western Europe . Twenty-two percent of patients were less than or equal to 6 months old, 69% were less than or equal to 12 months, 87% were less than or equal to 18 months, and 93% were less than or equal to 24 months . Thus, our findings represent a unique epidemiological pattern: 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 . In view of these data, the Israeli Ministry of Health decided to license conjugate vaccines for immunization of infants beginning at 2 months of age. Clin Infect Dis, 1992 Oct, 15(4), 716 - 9 Hepatobiliary infections caused by Haemophilus species; O'Bryan TA et al.; Haemophilus species are rarely associated with hepatobiliary infections . We report a case of hepatic abscess caused by Haemophilus paraphrophilus and review the English-language literature for reports of infections of the liver and biliary system caused by Haemophilus species . Most patients identified had predisposing conditions . The pathogenesis of hepatobiliary infections due to Haemophilus species may involve ascending spread from the gastrointestinal tract or hematogenous seeding following oropharyngeal colonization. Ann Thorac Surg, 1992 Oct, 54(4), 755 - 60 Surgical management of infective endocarditis in children; Citak M et al.; Infective endocarditis occurs infrequently in the general pediatric population, occurring mostly in patients with congenital heart disease . This study reviews our surgical experience with infective endocarditis based on a policy of aggressive intervention, conservative operative debridement, and creative reconstruction options using pericardium and prosthetic heart valves . From 1982 to 1989, 16 patients, 3 weeks to 16 years of age, underwent 19 intracardiac operations for infective endocarditis therapy at Kosair Children's Hospital . Eight (42%) were for resection of vegetations alone; an additional 11 operations (58%) involved more extensive debridements requiring either valve replacement or valvuloplasty using pericardium for exclusion of an abscess cavity, closure of a fistula, or for valve repair . Operative mortality was 25% (4 patients) and related to preoperative disease severity . There was one late death . Offending organisms included Staphylococcus species (31%), Haemophilus influenzae (13%), pneumococcus (5%), gram-negative organisms (13%), and Candida (13%); no organism grew on culture in 25% . We conclude that aggressive surgical exploration in patients with infective endocarditis is indicated and often requires resection of vegetations alone . More extensive procedures should preserve as much valvular tissue as possible . Pericardium is useful for reconstruction after debridement. Am J Dis Child, 1992 Oct, 146(10), 1160 - 5 Uses and technique of pediatric lumbar puncture; Ward E et al.; OBJECTIVES--To review diagnostic and therapeutic indications, contraindications, complications, and technique of pediatric lumbar puncture with emphasis on diagnosis of bacterial meningitis in bacteremia, cellulitis, and fever with seizures and to discuss cerebrospinal fluid findings in partially treated infection and traumatic blood-contaminated spinal tap . RESEARCH DESIGN--Literature review . CONCLUSIONS--We recommend lumbar puncture for children younger than 1 year with bacteremia, children with Haemophilus influenzae type B cellulitis, and children with fever and seizures not classified as simple . Pretreatment with antibiotics rarely changes cerebrospinal fluid characteristics such that a diagnosis of bacterial meningitis would be obscured . In a traumatic spinal tap, the equation to predict cerebrospinal fluid pleocytosis based on the peripheral blood cell count is invalid . When used together, cerebrospinal fluid glucose level, Gram's staining, and observed-to-expected ratio of white blood cells are highly reliable in diagnosing bacterial meningitis. South Med J, 1992 Oct, 85(10), 1015 - 6 Recurrent pneumococcal pneumonia in an HIV-positive patient with lymphoid interstitial pneumonitis; Harley W et al.; Lymphoid interstitial pneumonitis (LIP) is a rare complication of AIDS in adults . Patients with AIDS and LIP are at high risk for bacterial pneumonia caused by Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus . We have described an HIV-positive patient with LIP complicated by recurrent pneumonia due to Streptococcus pneumoniae; recurrence was apparently prevented by maintenance penicillin therapy. Pediatr Infect Dis J, 1992 Oct, 11(10), 855 - 9 IgG1, IgG2 and IgM responses to two Haemophilus influenzae type b conjugate vaccines in young infants; Ambrosino DM et al.; PRP-meningococcal outer membrane protein complex (PRP-OMPC) and oligosaccharide linked to variant diphtheria toxin (HbOC) Haemophilus influenzae type b (HIB) conjugate vaccines have both been licensed for United States infants at 2 months of age . Differences in serologic responses for these vaccines have been noted with PRP-OMPC producing an early response at 2 months of age and HbOC producing a higher response after a third dose at 6 months of age . To further characterize the nature of these distinct responses, we measured the IgG1, IgG2 and IgM anti-HIB concentrations by enzyme-linked immunosorbent assay after administration of both vaccines . PRP-OMPC produced an IgM and IgG1 anti-HIB response following the initial dose at 2 months of age . After two doses of HbOC an increase in IgG1 and IgM were noted and after a third dose at 6 months of age an IgG2 anti-HIB response occurred . In addition 33 study subjects were boosted with PRP-OMPC at age 18 months and compared with 34 subjects who received only a primary dose . The anti-HIB IgG1 and IgG2 concentrations following the booster dose were both significantly higher for the primed group (P = 0.0001 and P = 0.001, respectively) . Both HIB conjugate vaccines produce predominantly IgG1 anti-HIB antibody responses . The early response to PRP-OMPC vaccine at 2 months of age may result from adjuvant characteristics of the OMPC. J Med Microbiol, 1992 Oct, 37(4), 268 - 72 Association of Haemophilus ducreyi with cell-culture lines; Shah L et al.; The association of Haemophilus ducreyi with epithelial cell cultures was studied by light microscopy, electronmicroscopy and viable counts . Associated organisms were engulfed by epithelial cells and sequestered from the cell-surface environment . Large numbers of organisms within epithelial cells appeared to induce cell lysis and release of H . ducreyi . Such a mechanism occurring in vivo may assist H . ducreyi to evade the bactericidal action of polymorphonuclear leucocytes and may explain some of the tissue damage seen in genital ulcers caused by H . ducreyi. J Bacteriol, 1992 Oct, 174(20), 6455 - 9 Generation of lipooligosaccharide mutants of Haemophilus influenzae type b; McLaughlin R et al.; We previously reported the analysis of recombinant plasmids from Haemophilus influenzae type b (Hib) that lead to modifications of Escherichia coli lipopolysaccharide (LPS) (Y . Abu Kwaik, R . E . McLaughlin, M . A . Apicella, and S . M . Spinola, Mol . Microbiol . 5:2475-2480, 1991) . The modified LPS species are recognized by monoclonal antibodies (MAbs) 6E4 and 3F11 . MAb 6E4 binds to a stable 2-keto-3-deoxyoctulosonic acid epitope, while MAb 3F11 binds to a Gal beta 1-4GlcNac epitope that phase varies in Hib at a frequency of 2 to 5% . The internal EcoRI fragment containing most of the DNA required for LPS modification in E . coli was used as the target for transposon mutagenesis . Plasmids containing minitransposon m-Tn3(Cm) randomly inserted into the target fragment were transformed into the isogenic Hib strain, and transposon integration into the Hib chromosome was verified by colony hybridization . The lipooligosaccharides of 36 transformants were phenotypically and antigenically characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and reactivity with a variety of MAbs that recognize both stable and phase-varying lipooligosaccharide epitopes . The majority of the mutants had altered reactivity with MAb 6E4 . With one exception, these mutants retained the ability to express phase-varying epitopes . Analysis of the transformants suggested that the 6E4 epitope was contained on an oligosaccharide chain separate from that of phase-varying epitopes and appeared to be assembled in at least three separate steps. J Bacteriol, 1992 Oct, 174(20), 6674 - 7 Site-specific integration of the Haemophilus influenzae bacteriophage HP1: location of the boundaries of the phage attachment site; Hauser MA et al.; Plasmids containing DNA segments from the attachment region of phage HP1 were constructed and tested for the ability to replace the phage attachment site substrate in site-specific recombination reactions . The distance separating the boundaries of the functional site was 418 bp . Replacements within the 11-residue segment 5'-GGCGGTTATCG at the left boundary or within the 12-residue segment 5'-GGATTTTTTGAA at the right boundary abolished substrate activity . A segment of the 418-residue sequence preserves the integrity of an operon of three Haemophilus influenzae tRNA genes after HP1 insertion within the coding sequence. Infect Immun, 1992 Oct, 60(10), 4111 - 8 Molecular analysis of the Haemophilus ducreyi groE heat shock operon; Parsons LM et al.; Chancroid is a sexually transmitted genital ulcer disease caused by Haemophilus ducreyi . Previously, we developed diagnostic DNA probes for H . ducreyi (L . M . Parsons, M . Shayegani, A . L . Waring, and L . H . Bopp, J . Clin . Microbiol . 27:1441-1445, 1989) . In the present study, DNA sequencing of one of the diagnostic probes revealed two adjacent open reading frames (ORFs) . These H . ducreyi ORFs and the encoded proteins show significant homology with the groE genes and GroES and GroEL heat shock proteins from several bacterial pathogens and with conserved eukaryotic 60-kDa heat shock proteins . The first H . ducreyi ORF (groES) is preceded by sequences similar to those of the Escherichia coli consensus heat shock promoters and is 288 nucleotides long and is capable of encoding a protein of 10.3 kDa . The second ORF (groEL) is 1,641 nucleotides long and is capable of encoding a protein of 57.8 kDa . Northern (RNA blot) analysis demonstrated the presence of a high level of groE mRNA in exponential-phase H . ducreyi grown in hemin broth at the organism's optimal growth temperature (33 degrees C), with increased levels seen following heat shock . Heat shock also increased the thermostability of the organisms, since stressed cells were more resistant to the lethal effects of rapid chilling . Electrophoretic analysis and immunoblots demonstrated that the predominant protein produced by exponential-phase H . ducreyi was a heat-inducible, immunoreactive protein of approximately 60 kDa (GroEL) . Also, H . ducreyi groE mRNA and GroEL were expressed and inducible by heat in E . coli . This is the first report describing the cloning, sequencing, and expression of H . ducreyi protein-encoding genes. Antimicrob Agents Chemother, 1992 Oct, 36(10), 2185 - 91 Comparative in vitro activities of a new quinolone, OPC-17116, possessing potent activity against gram-positive bacteria; Wakebe H et al.; The in vitro antibacterial activity of OPC-17116, a new fluoroquinolone, against a wide variety of clinical isolates was evaluated and compared with those of ciprofloxacin, ofloxacin, and norfloxacin . OPC-17116 showed potent broad-spectrum activity against gram-positive and -negative bacteria . The activity of this compound against gram-positive bacteria was higher than those of other quinolones, and its activity against gram-negative and anaerobic bacteria was roughly comparable to those of other quinolones . OPC-17116 had potent activity against important pathogens of respiratory tract infections such as Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Haemophilus influenzae, and Branhamella catarrhalis . The MICs of this compound against 90% of these organisms, except for methicillin-resistant S . aureus, ranged from less than or equal to 0.006 to 3.13 micrograms/ml . OPC-17116 at more than one-half the MICs was bactericidal against clinical isolates of S . aureus, Escherichia coli, K . pneumoniae, and P . aeruginosa . The activity of OPC-17116 was decreased by several culture conditions such as acidic pH, high concentration of Mg2+ ions, and inoculum size of 10(7) CFU/ml . OPC-17116 inhibited the supercoiling activity of DNA gyrases from E . coli KL-16 and S . aureus SA113 (50% inhibitory concentrations, 0.19 and 23.0 micrograms/ml, respectively) . The amount of OPC-17116 accumulation was higher than that of other quinolones in S . aureus. Infect Immun, 1992 Oct, 60(10), 4024 - 31 Modification in penicillin-binding proteins during in vivo development of genetic competence of Haemophilus influenzae is associated with a rapid change in the physiological state of cells; Dargis M et al.; By using whole-cell labeling assay with 125I-penicillin V, we observed a reduction in the binding of the radiolabeled beta-lactam to four or five penicillin-binding proteins (PBPs) in Haemophilus influenzae cells cultivated under specific conditions . PBPs 3A, 3B, 4, and 6 were altered after the growth of bacteria in diffusion chambers implanted in the peritoneal cavity of rats . PBP 2 was also modified when cells were cultivated in human cerebrospinal fluids . Because this observation may have important consequences on the efficacy of beta-lactams during antibiotic therapy, we characterized the physiological state of bacteria cultivated in animals in the hope of explaining how such important changes in cell properties develop in vivo . Since the development of natural genetic competence occurs at the stationary phase of growth in H . influenzae, we used a DNA transformation assay to evaluate the physiological state of bacteria grown in diffusion chambers implanted in rats . Chromosomal DNA isolated from an antibiotic-resistant donor strain was mixed with bacteria in diffusion chambers . At different times during a 5-h incubation period, recipient bacteria were collected from the chambers, CFU were determined by plate counting, and antibiotic-resistant transformants were isolated on selective plates . Genetic competence rapidly developed in cells grown in rats, and the frequency of transformation by test DNA was elevated . Electron microscopy revealed an irregular cell shape and blebs at the surface of bacteria cultivated in animals and in cerebrospinal fluids . In an attempt to induce a similar physiological state in vitro, we supplemented broth cultures with cyclic AMP or synchronized cultures by a nutritional upshift . No changes in PBPs were observed with supplemental cyclic AMP or during a single cell cycle . Finally, a reduction in the affinity of PBPs for 125I-penicillin V identical to that observed in bacteria grown in rats was observed in cells isolated from the stationary phase of growth in vitro . These results clearly indicate that H . influenzae cells grown in animals undergo a rapid change to a physiological state similar to that found in late-stationary-phase cultures in vitro . This observation indicates that the rational design of future and improved antibiotic therapy of H . influenzae infections should consider cell properties of slow-growing or latent bacteria. Mol Microbiol, 1992 Oct, 6(20), 3051 - 63 The gal locus from Haemophilus influenzae: cloning, sequencing and the use of gal mutants to study lipopolysaccharide; Maskell DJ et al.; The gal locus from Haemophilus influenzae was cloned and sequenced . Four genes were identified by amino acid homology: galT, galK, galM and galR . The coding direction of galT, galK and galM is divergent from that of galR . There are non-coding intergenic regions between galR and galT, galT nd galK, and galK and galM . Deletion-insertion mutations constructed in galK and galE, which is in lic3, were moved into the H . influenzae chromosome generating each of the single mutants as well as the double gal mutant . Even when grown on complex media, the double mutant failed to react with an anti-lipopolysaccharide monoclonal antibody known to react with a digalactoside epitope . Both the galE single and the galE galK double mutants were serum-sensitive and relatively avirulent in infant rats, indicating a critical role for galactose metabolism, and providing evidence to support a central role for lipopolysaccharide, in H . influenzae virulence. Br Med Bull, 1992 Oct, 48(4), 912 - 30 Microbiology of lung infection in cystic fibrosis; Govan JR et al.; Bronchopulmonary infection in cystic fibrosis (CF) patients is associated with chronic progressive lung disease and episodes of acute exacerbation . Infection is predominantly caused by bacteria, although infections with viruses, mycoplasma and fungi may play undervalued roles . Bacteria commonly isolated from CF sputum include Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa . Colonisation of the airways by mucoid, alginate-producing variants of P . aeruginosa is recognised as a major cause of pulmonary deterioration . In addition, there is now considerable concern relating to the clinical consequences of colonisation and cross-infection with P . cepacia . This review discusses the microbiology of CF focussing on the pathogenesis and epidemiology of P . aeruginosa and P . cepacia. Med Clin (Barc), 1992 Sep 26, 99(9), 324 - 6 {Haemophilus influenzae pulmonary infection in patients infected with the human immunodeficiency virus}; Tudela P et al.; BACKGROUND: Haemophilus influenzae has frequently been identified as the etiologic agent in pneumonias of patients with the human immunodeficiency virus (HIV) infection . The experience of the authors is reviewed and the significance of isolating this microorganism in respiratory samples commented upon . METHODS: The clinical, radiological and microbiological data of patients with HIV infection in whom H . influenzae was identified in blood, lung tissue, or samples of the lower respiratory tract obtained by fibrobronchoscopy were retrospectively evaluated . RESULTS: Twenty cases were diagnosed with 75% presenting bilateral lung infiltration . In 70% the isolation sample was that of bronchoalveolar lavage . In 40% of the total another microorganism was identified in coinfection with H . influenzae, of which Mycobacterium tuberculosis was the most frequent . Thirty-five percent of the cases presented antecedents of one or several previous pulmonary infections . H . influenzae infection was not observed with either concomitant or previous infections in 20% of the patients . CONCLUSIONS: A high frequency of pneumonias by Haemophilus influenzae with bilateral radiologic presentation have been found . H . influenzae is frequently demonstrated as in coinfection with other agents . The role that this microorganism has in pulmonary infection of patients with HIV infection is not clearly defined. Rev Prat, 1992 Sep 15, 42(14), 1797 - 803 {Infectious risk in day-nursery children}; Collet JP et al.; High proximity in daycare centers is a well established risk factor for upper respiratory tract infections as well as Haemophilus influenza meningitis . Many studies have also reported the development of gastroenteritis as well as hepatitis A outbreaks in daycare centers; however, because of lack of controls, these studies do not provide enough information about the excess of risk attributable to daycare attendance . Main risk factors such as age, or seasons, are still very important in daycare centers and studies have also shown that a protection occurs rapidly after the beginning of attendance, may be in relation to the stimulation of the non-specific immunity . All these results do not provide enough data to implement a rational intervention project . More studies have to be carried out to assess the long term consequences (at school age for instance) of these infections . In order to make a rational decision regarding daycare attendance, it is important to have a global assessment of all the effects related to attendance (which are numerous and sometimes opposite); studies focusing on a single aspect of daycare attendance, or on its short term effect, may result in partial and misleading conclusions. J Allergy Clin Immunol, 1992 Sep, 90(3 Pt 2), 457 - 61; discussion 462 The microbial etiology and antimicrobial therapy of adults with acute community-acquired sinusitis: a fifteen-year experience at the University of Virginia and review of other selected studies; Gwaltney JM Jr et al.; Pretreatment sinus puncture was performed on 339 patients with acute community-acquired sinusitis (ACAS) between 1975 and 1990 . Bacterial species recovered in titers of greater than or equal to 10(4) colony-forming units per milliliter (CFU/ml) from 383 sinus aspirates included Streptococcus pneumoniae, 92 (41%); Haemophilus influenzae, 79 (35%); anaerobes, 17 (7%); streptococcal species, 16 (7%); Moraxella catarrhalis, 8 (4%); Staphylococcus aureus, 7 (33%); and other, 8 (4%) . Viruses (rhinovirus, parainfluenza virus, and influenza virus) and fungi (Aspergillus, zygomycoses, Phaeohyphomycis, Pseudallescheria, and Hyalohyphomycis) have also been reported to cause ACAS . Posttreatment sinus puncture was performed on 220 of the 339 patients in six studies to evaluate efficacy of selected antimicrobial agents in producing bacteriologic cure . Ampicillin, 500 mg four times daily; amoxicillin, 500 mg three times daily; trimethoprim-sulfamethoxazole, twice a day; cefaclor, 500 mg four times daily; bacampicillin, 800 mg twice a day; cyclacillin, 500 mg three times a day; cefuroxime axetil, 250 mg twice daily; amoxicillin-clavulanate, 500/125 three times daily; and loracarbef 400 mg twice daily, given in 10-day courses, produced bacteriologic cure in more than 90% of patients . Early studies were done before beta-lactamase-producing strains of H . influenzae were a frequent cause of ACAS in Charlottesville . Management of therapeutic failures is a difficult problem for which diagnostic and therapeutic sinus puncture and lavage, prolonged antimicrobial therapy, steroid therapy, and evaluation of allergy, immunodeficiency, and surgically correctable lesions of the osteomeatal complex are recommended. Mol Microbiol, 1992 Sep, 6(18), 2583 - 8 Construction of chimaeric genes for mapping a surface-exposed epitope on the pilus of non-typable Haemophilus influenzae strain M37; Palmer KL et al.; A murine monoclonal antibody (mAb), designated 3H12, reacts with a surface-exposed conformational epitope on the pilus of non-typable Haemophilus influenzae strain M37 . This antibody does not recognize the related pilus from H . influenzae type b, strain MinnA . Although mAb 3H12 does not recognize strain M37 pilin on Western blots, mAb 3H12 recognizes the recombinant M37 pilin protein expressed by Escherichia coli . In order to map the epitope recognized by mAb 3H12, we constructed a series of chimaeric genes . The chimaeric genes were expressed in E . coli and the chimaeric proteins characterized with respect to their reactivity with mAb 3H12 . Residues between 37 and 100 of the M37 pilin protein are essential for the expression of the mAb 3H12 epitope . Residues in the carboxyl half of the M37 protein enhance the reactivity of mAb 3H12 when expressed in the presence of residues 37-100 . Construction of chimaeric genes may provide a general methodology for mapping of conformational epitopes expressed by one of a related pair of proteins. Tidsskr Nor Laegeforen, 1992 Sep 10, 112(21), 2747 - 50 {Bacteriological examination of bronchial aspirates obtained via fiberoptic bronchoscopy}; Borchsenius F et al.; We present the bacteriological findings in 329 aspirates from fiberoptic bronchoscopy . Quantitative cultures were not performed . 92 of the patients had radiologically confirmed pneumonia, 58 possibly had infectious bronchitis or pneumonia which was not verified radiologically, 154 had other pulmonary diseases and 25 had no verified pulmonary disease . 13% of aspirates contained no bacterial isolates and 33% revealed growth of multiple bacteria, classified as "normal pharyngeal flora" . Among the 54% with specified bacterial findings the most frequent bacteria were viridans streptococci, staphylococci, Haemophilus influenzae, and Streptococcus pneumoniae . The differences in bacterial flora between the patient groups were only minimal . Klebsiella and Escherichia coli were the only bacteria indicating presence of pneumonia . S pneumoniae were found more frequently among patients with no signs of infection . Bronchial aspirates obtained with a fiberbronchoscope may give false positive results and are of limited value in diagnosing pneumonia . However, the presence of gram negative intestinal rods may indicate bacterial respiratory infection in hospitalized patients . Improving sampling and culture techniques can possibly improve the value of bacteriological findings. Lancet, 1992 Sep 5, 340(8819), 592 - 4 Rapid disappearance of Haemophilus influenzae type b meningitis after routine childhood immunisation with conjugate vaccines; Peltola H et al.; Mortality from meningitis caused by Haemophilus influenzae type b (Hib), a disease that affects mainly infants and young children, can reach 5% in industrialised countries and ten times that in non-industrialised countries . To determine the efficacy of vaccination against Hib, we carried out a retrospective survey of the incidence of Hib meningitis over five decades in the Greater Helsinki area of Finland, where all children with bacterial meningitis are treated in one of three centres . Except for a meningococcal epidemic in the early 1970s, Hib was the leading cause of childhood bacterial meningitis until the Hib conjugate vaccines changed the picture profoundly . In 1986-87 the polysaccharide-diphtheria toxoid conjugate (PRP-D) was given experimentally to 50% of infants . In 1988-89 all infants were vaccinated, 50% with PRP-D, 50% with another conjugate vaccine, the oligosaccharide-CRM197 protein conjugate (HbOC) . Since 1990 a third conjugate vaccine, the polysaccharide-tetanus toxoid (PRP-T), has been administered routinely to all infants . The vaccines were administered at age 3-6 months, with a booster dose at 14-18 months . In the first 5 years of the Hib vaccination programme the number of cases of Hib meningitis in children aged 0-4 years fell sharply, from 30 in 1986 (the first year of the programme) to none in 1991 . The decline contrasts sharply with the rising trend up to the mid 1980s . Vaccination seems to be the only explanation for the observed change in the epidemiology of Hib meningitis. J Allergy Clin Immunol, 1992 Sep, 90(3 Pt 2), 469 - 73 Antimicrobial therapy of pediatric patients with sinusitis; Wald ER; The mainstay of medical therapy for acute and subacute sinusitis is the selection of an antimicrobial agent based on an appreciation of the usual bacterial pathogens that include Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis . Amoxicillin is appropriate therapy for patients with uncomplicated sinusitis in geographic areas in which the prevalence of beta-lactamase-producing pathogens is less than 20% . If a patient does not respond to amoxicillin or in areas in which there is a high prevalence of beta-lactamase-producing bacterial species, alternative antimicrobials include amoxicillin-clavulanate, erythromycin-sulfisoxazole, trimethoprim-sulfamethoxazole, cefaclor, cefuroxime axetil, and cefixime . Cefixime, which is less active against S . pneumoniae than most of these antimicrobials, should be reserved for patients who do not improve with amoxicillin . Amoxicillin-potassium clavulanate, cefuroxime axetil, and erythromycin-sulfisoxazole have the most comprehensive antibacterial spectra. J Allergy Clin Immunol, 1992 Sep, 90(3 Pt 2), 452 - 6 Microbiology of acute and chronic sinusitis in children; Wald ER; To determine the bacteriologic cause of acute sinusitis, a sample of sinus secretions must be obtained from one of the paranasal sinuses without contamination by normal respiratory or oral flora that colonize mucosal surfaces . When maxillary sinus aspiration is performed on children who have signs and symptoms of acute sinusitis, bacteria are recovered in high density from 70% . In patients with acute, subacute, or chronic sinusitis who are generally well except for persistent respiratory symptoms, of nasal discharge or cough or both, the usual bacterial isolates are Streptococcus pneumoniae, Haemophilus influenzae, an Moraxella catarrhalis . In contrast, anaerobic organisms and staphylococci should be suspected in patients who have very long-standing symptoms or in those whose symptoms are so severe or complicated that sinus surgery is undertaken. Am J Med, 1992 Sep, 93(3), 271 - 6 Clinical comparison of cefuroxime axetil and amoxicillin/clavulanate in the treatment of patients with acute bacterial maxillary sinusitis; Camacho AE et al.; PURPOSE: This multicenter study compared the clinical and bacteriologic efficacy of two oral antibiotics, cefuroxime axetil and amoxicillin/clavulanate, in the treatment of acute bacterial maxillary sinusitis . PATIENTS AND METHODS: Three hundred seventeen patients with clinical and radiographic evidence of acute maxillary sinusitis were enrolled at nine centers and were randomly assigned to receive 10 days of treatment with cefuroxime axetil 250 mg twice daily (n = 157) or amoxicillin/clavulanate 500 mg three times daily (n = 160) . Patients were assessed for both clinical and bacteriologic responses once during treatment (5 to 7 days) and twice after treatment (1 to 3 days and 4 weeks) . Bacteriologic assessments were based on needle aspirates of the maxillary sinus obtained pretreatment and, when possible, at the first posttreatment visit . RESULTS: Organisms were isolated from the pretreatment sinus aspirates of 198 of 317 (62%) patients, with the primary isolates being Streptococcus pneumoniae (22%), Haemophilus spp . (17%), Staphylococcus aureus (13%), and Haemophilus influenzae (10%) . A satisfactory clinical outcome (cure or improvement) was achieved in 85% (98 of 115) and 82% (102 of 124) of the clinically evaluable patients treated with cefuroxime axetil or amoxicillin/clavulanate, respectively (P = 0.446) . With respect to the eradication of the bacterial pathogens, a satisfactory outcome (cure or presumed cure) was obtained in 84% (31 of 37) and 87% (34 of 39) of bacteriologically evaluable patients treated with cefuroxime axetil or amoxicillin/clavulanate, respectively (p = 0.567) . Treatment with amoxicillin/clavulanate was associated with a significantly higher incidence of drug-related adverse events (13% versus 3%, p = 0.001), particularly diarrhea (8% versus 1%, p = 0.001) . Two patients in the cefuroxime axetil group and three patients in the amoxicillin/clavulanate group withdrew from the study due to adverse events . CONCLUSIONS: Our results indicate that cefuroxime axetil twice a day is as effective as amoxicillin/clavulanate three times a day in the treatment of acute bacterial maxillary sinusitis but produces fewer adverse effects. J Pediatr, 1992 Sep, 121(3), 355 - 62 Efficacy and safety of a Haemophilus influenzae type b capsular polysaccharide-tetanus protein conjugate vaccine; Fritzell B et al.; A polyribosylribitol phosphate (polysaccharide)-tetanus protein conjugate vaccine (PRP-T) against Haemophilus influenzae type b (Hib) was evaluated for safety and efficacy after vaccination of more than 100,000 infants . No major side effects were attributed to the vaccine . Immunogenicity studies showed an antibody response in 70% to 100% of infants after two doses, and in 98% to 100% of infants after three doses, within the first 6 months of life . Antibodies persisted in 90% of recipients, in whom significant anamnestic responses developed after a booster dose at 18 months of age . In comparison with other available Hib vaccines, PRP-T induces equal or higher mean titers after three doses . Although licensure of other vaccines interrupted controlled efficacy trials, up to that point five cases of Hib disease in those trials had occurred in placebo recipients, and no Hib disease has been reported in the more than 100,000 vaccinated infants who have received more than one dose of PRP-T . Thus PRP-T combined immunogenicity early in life with induction of immunologic memory. J Bacteriol, 1992 Sep, 174(17), 5604 - 8 Cloning, characterization, and DNA base sequence of the high-level streptomycin resistance gene strA1 of Haemophilus influenzae Rd; Stuy JH et al.; The high-level streptomycin resistance strA1 gene of Haemophilus influenzae Rd was cloned in plasmid pAT4 as a 2.1-kbp EcoRI insert . It was later replaced in pAT4 by the wild-type strA+ gene . Plasmid pAT4 carrying the strA+ gene is highly unstable and renders chromosomally resistant recipients sensitive to streptomycin . The strA+ gene and the instability factor both reside on a 500-base HindIII-EcoRI subfragment . The two biological activities are also expressed in Escherichia coli . Both wild-type (strA+) and mutant (strA1) genes were sequenced . They show considerable nucleotide homology with the E . coli strA+ gene and its product. Indian J Med Res, 1992 Sep, 95, 230 - 3 Occurrence of multiple antimicrobial resistance among Haemophilus influenzae type b causing meningitis; Singh R et al.; Among the 157 children with culture proven pyogenic meningitis who were admitted during 1987-1991, in the Department of Child Health at the Christian Medical College and Hospital, Vellore, 40 had H . influenzae type b (HIB) meningitis; 17 of these had multiantimicrobial resistant HIB (MRHIB) and 23 others had usual susceptibility HIB (USHIB) meningitis . The two groups were compared . Children with MRHIB meningitis who received optimal treatment with cefotaxime had excellent recovery . When cefotaxime therapy was delayed, mortality was noted in all except one child who survived with severe neurological sequelae . MRHIB meningitis treated with drugs other than cefotaxime had 100 per cent mortality . Cefotaxime is therefore recommended in children below 3 yr of age presenting with purulent meningitis, as MRHIB is a possible causative agent in this group. Can J Microbiol, 1992 Sep, 38(9), 958 - 68 Effect of oxygen supply during growth on the production of cytochromes, enzymes, and acid end products by Haemophilus parasuis; Martin PG et al.; Haemophilus parasuis, grown under conditions of high aeration, was found to lack a tricarboxylic acid cycle but to possess phosphoenolpyruvate carboxylase and a reductive pathway leading to the production of succinate . Such organisms contained approximately equal quantities of b-, c-, and d-type cytochromes and excreted acetate . When the oxygen supply for growth was either reduced or eliminated, the specific activities of phosphoenolpyruvate carboxylase, malate dehydrogenase, fumarase, fumarate reductase, and NADH: fumarate oxidoreductase were increased substantially, and the acid products were succinate, acetate, and formate . Organisms grown under the latter conditions also contained increased quantities of b- and c-type cytochromes, some of which were low-potential cytochromes . These low-potential cytochromes were reduced by NADH and oxidized by fumarate, and hence, appeared to be components of NADH: furmarate oxidoreductase . Our results indicate that in H . parasuis, growing aerobically in medium containing glucose, the sole function of the reductive pathway is to provide intermediates for biosynthetic processes, and oxygen is the preferred electron acceptor . As the supply of oxygen is reduced or eliminated, the reductive pathway becomes more involved in NAD+ recycling and fumarate becomes the acceptor . In effect, irrespective of the oxygen supply, the growth of H . parasuis is absolutely dependent upon the presence of an electron transport system. J Antimicrob Chemother, 1992 Sep, 30(3), 377 - 85 Bronchoalveolar distribution of cefuroxime axetil and in-vitro efficacy of observed concentrations against respiratory pathogens; Baldwin DR et al.; The concentrations of cefuroxime in human alveolar macrophages (AM), epithelial lining fluid (ELF), bronchial mucosal biopsies and serum were measured after a single dose, equivalent to 500 mg of cefuroxime base, given in the form of the orally-administered pro-drug, cefuroxime axetil . Fourteen patients undergoing fibreoptic bronchoscopy with bronchoalveolar lavage were studied . The mean ELF concentration was 0.7 mg/L, that of bronchial biopsies was 1.8 mg/kg and that of serum 3.5 mg/L . AM-associated cefuroxime was detected in nine patients . To assess the in-vitro activity of the concentrations achieved at the potential sites of infection, clinical isolates of common respiratory pathogens were exposed to two concentrations of cefuroxime, based on the observed concentrations in ELF and bronchial mucosa . ELF and mucosal site concentrations were effective against Streptococcus pneumoniae (except one strain with reduced susceptibility to benzyl penicillin) and Haemophilus influenzae . The ELF concentration was less effective against Moraxella catarrhalis. J Antimicrob Chemother, 1992 Sep, 30(3), 261 - 72 Antibacterial profile of flurithromycin, a new macrolide; Saverino D et al.; The in-vitro activity of flurithromycin against common respiratory tract Gram-positive (85 strains) and Gram-negative (44 strains) pathogens, and a collection of anaerobes (125 strains) was compared with that of erythromycin, cefixime, amoxycillin, co-amoxiclav, ciprofloxacin, netilmicin and clindamycin . Flurithromycin possessed the same spectrum and potency of antimicrobial activity as erythromycin . The presence of 50% human serum in the test media enhanced the activity of flurithromycin against all isolates, with the exception of Streptococcus pyogenes . Flurithromycin induced a post-antibiotic effect (PAE) that ranged from 0.25 h (Haemophilus influenzae) to 3.5 h (Streptococcus pneumoniae) for all strains tested . The presence of serum increased or diminished the duration of the PAE, depending on the strain being analysed . No interaction between flurithromycin and the other drugs tested was observed by the checkerboard technique, but when the time-kill system was used, 35 cases of synergy were noted out of 120 tests performed (29%), of which 15 (43%) were with Moraxella catarrhalis, 12 (34%) with Staphylococcus aureus, four (11%) with H . influenzae and the remainder with S . pneumoniae and S . pyogenes . Netilmicin produced most synergic interactions . Antagonism was not detected by either methods. Pediatr Infect Dis J, 1992 Sep, 11(9), 717 - 21 Comparative efficacy of oral rifampin and topical chloramphenicol in eradicating conjunctival carriage of Haemophilus influenzae biogroup aegyptius . Brazilian Purpuric Fever Study Group; Perkins BA et al.; Persistent conjunctival carriage of the Haemophilus influenzae biogroup aegyptius (Hae) strain (BPF clone) responsible for Brazilian purpuric fever (BPF) has been documented . Topical chloramphenicol is routinely used to treat conjunctivitis in areas affected by BPF in Brazil . Although the BPF clone is susceptible to chloramphenicol, we observed a number of children treated with topical chloramphenicol for conjunctivitis who still developed BPF . During an investigation of an outbreak of BPF in Mato Grosso State, Brazil, we compared oral rifampin (20 mg/kg/day for 4 days) with topical chloramphenicol for eradication of conjunctival carriage of H . influenzae biogroup aegyptius among children with presumed BPF clone conjunctivitis . Conjunctival samples were taken for culture on the day treatment was initiated and a mean of 8 and 21 days later . At 8 days the eradication rates for oral rifampin and topical chloramphenicol were 100 and 44%, respectively (P = 0.003); at 21 days they were 100 and 50% (P = 0.01) . Oral rifampin was more effective than topical chloramphenicol for eradication of the BPF clone and may be useful in prevention of BPF. Photochem Photobiol, 1992 Sep, 56(3), 341 - 52 The phototoxicity of 8-methoxythionepsoralen and 6-methylthionecoumarin; Tuveson RW et al.; The phototoxicity of 8-methoxythionepsoralen (8-MOTP) and 6-methylthione coumarin (6-MTC) when activated by UV-A has been investigated using a variety of Escherichia coli strains, Haemophilus influenzae transforming DNA and Escherichia coli pBR322 plasmid DNA . The results demonstrate that 8-MOTP is a strictly oxygen independent photosensitizer that is about 500-fold less efficient in forming lesions leading to equivalent lethality than is the parent compound from which it is derived (8-MOP) . As is true for 8-MOP, 8-MOTP is capable of inducing histidine independent mutations in E . coli and inactivating transforming DNA consistent with DNA being a target for lesions induced by this molecule in the presence of UV-A . 6-MTC is a strongly oxygen dependent photosensitizer activated by UV-A when tested with either E . coli cells or transforming DNA in contrast to the parent compound (6-methylcoumarin; 6-MC) which is not phototoxic when treated with UV-A . These results imply that the membrane may be an important target leading to lethality . 6-MTC in the presence of UV-A can inactivate pBR322 plasmid and Haemophilus influenzae transforming DNA activity in vitro suggesting that DNA is a potential target for this molecule when activated by UV-A. J Infect, 1992 Sep, 25(2), 197 - 200 Haemophilus influenzae type b purpura fulminans treated with hyperbaric oxygen; Dollberg S et al.; We report the case of a 4-month-old child with purpura fulminans caused by Haemophilus influenzae type b . In addition to conventional therapy, she was treated with hyperbaric oxygen, and made a full recovery . Hyperbaric oxygen as an adjunct to other therapy in purpura fulminans is discussed. Diagn Microbiol Infect Dis, 1992 Sep-Oct, 15(7), 633 - 40 In vitro activity of cefprozil (BMY 28100) and cefepime (BMY 28142) against Streptococcus pneumoniae, Branhamella catarrhalis, and Haemophilus influenzae, and provisional interpretive criteria for disk diffusion and dilution susceptibility tests with Haemophilus influenzae; Doern GV et al.; The in vitro activities of two new cephalosporins, an oral agent, cefprozil and a parenteral compound, cefepime, were assessed against recent clinical isolates of Streptococcus pneumoniae, Moraxella (Branhamella) catarrhalis, and Haemophilus influenzae . In general, both cefprozil and cefepime MICs were higher for beta-lactamase-producing strains of M . catarrhalis in comparison to strains that lacked beta-lactamase . By contrast, beta-lactamase-positive and -negative strains of H . influenzae had similar cefprozil and cefepime minimum inhibitory concentrations (MICs) . The MIC90 values for cefprozil were 0.12, 32, 4.0, and 0.5 micrograms/ml versus S . pneumoniae, H . influenzae, and beta-lactamase-positive and negative strains of M . catarrhalis, respectively . In comparison to three other oral cephalosporins included in this study, cefaclor, cefuroxime axetil, and cefixime, cefprozil was the most active agent against S . pneumoniae, the least active against B . catarrhalis, and equivalent in activity to cefaclor against H . influenzae . The cefepime MIC values against S . pneumoniae, H . influenzae, and beta-lactamase-positive and negative strains of M . catarrhalis were 0.03, 0.25, 2.0, and 0.5 micrograms/ml, respectively . Cefepime was less active than ceftriaxone for all three organism groups, however, was in all cases more active than cefixime, cefuroxime, cefaclor, and cefprozil.(ABSTRACT TRUNCATED AT 250 WORDS) Sex Transm Dis, 1992 Sep-Oct, 19(5), 291 - 4 Treatment of chancroid with a single dose of spectinomycin; Guzman M et al.; Fifty patients with lesions characteristic of chancroid were enrolled in an open-label prospective study to examine the efficacy of a single 2-gm dose of spectinomycin for treatment of chancroid . Only those patients (41 men; aged 18 to 49 years) with positive culture results for Haemophilus ducreyi were included in the analysis . Patients each received a single 2-gm dose of spectinomycin intramuscularly . The recovery process began on the third day of follow-up, as evidenced by the occurrence of epithelialization and a decrease in inflammation . By the seventh day after treatment, only one patient had ulcers; 40 patients experienced eradication of all ulcers (P less than 0.0001) . The condition of nodes affected by infection also indicated efficacy of treatment (P less than 0.01); only one patient still had a swollen node by the fourteenth day after treatment . Of the 41 patients, 37 (90%) had negative culture results for H . ducreyi on the third day after treatment . Only 4 patients (10%) required a second dose of spectinomycin on the seventh day to affect a cure . Treatment with spectinomycin resulted in a 98% cure rate 14 days after treatment . The minimum inhibitory concentration (MIC) of spectinomycin was 1 microgram/mL to 3 micrograms/mL in the 15 strains studied . The drug was well tolerated and no adverse reactions were reported . It is concluded that a single 2-gm dose of spectinomycin is a safe and effective alternative drug for treatment of chancroid. J Clin Microbiol, 1992 Sep, 30(9), 2495 - 7 Haemophilus influenzae is frequently detected with monoclonal antibody 8BD9 in sputum samples from patients with cystic fibrosis; Moller LV et al.; To determine the frequency of Haemophilus influenzae in sputum from patients with cystic fibrosis (CF), 477 sputum samples obtained from 86 CF patients were analyzed by standard culture and by the in situ immunoperoxidase staining technique with monoclonal antibody 8BD9 . H . influenzae was isolated from 109 sputum samples (23%) from 45 patients (52%) and detected by immunoperoxidase staining in 175 sputum samples (37%) obtained from 63 patients (73%) . The results of this study demonstrate the frequent presence of H . influenzae in sputum samples from CF patients. J Clin Microbiol, 1992 Sep, 30(9), 2284 - 9 Broth microdilution testing of Haemophilus influenzae with haemophilus test medium versus lysed horse blood broth . Canadian Haemophilus Study Group; Scriver SR et al.; Broth microdilution testing of 702 community-acquired isolates of Haemophilus influenzae from across Canada was performed with both Mueller-Hinton broth supplemented with 3% lysed horse blood broth (LHB) (BBL Microbiology Systems, Cockeysville, Md.) and haemophilus test medium (HTM) . The prevalence of beta-lactamase production was found to be 26% with no regional variation . MICs determined with LHB tended to be higher than those with HTM, but interpretive errors due to these differences were observed only rarely with trimethoprim-sulfamethoxazole (n = 5), cefaclor (n = 8), and cefamandole (n = 3) . The interobserver variability in MIC determinations was found to be greater when LHB was used than when HTM was used . There was no difference in intraobserver variability between the two medium formulations . beta-Lactamase-positive isolates developed false resistance to amoxicillin-clavulanate 2 weeks after microdilution panels of both types of medium were stored at -20 degrees C but not when panels were stored at -70 degrees C . In conclusion, this study supports the use of HTM rather than LHB for sensitivity testing of H . influenzae because of its lower rate of interobserver variability and its ability to support the growth of these organisms, which is comparable to that of LHB. J Clin Microbiol, 1992 Sep, 30(9), 2225 - 9 Growth of Porphyromonas gingivalis, Treponema denticola, T . pectinovorum, T . socranskii, and T . vincentii in a chemically defined medium; Wyss C; A chemically defined medium, OMIZ (Oral Microbiology and Immunology, Zurich)-W1 was developed . Medium OMIZ-W1 supports the long-term proliferation of a wide range of oral anaerobes, including representative strains of four Treponema species and Porphyromonas gingivalis . High concentrations of ascorbic acid and ammonium ions proved to be important for the growth of these organisms . T . denticola CD-1 grew in the absence of polyamines and long-chain fatty acids, T . pectinovorum and T . socranskii required polyamines, whereas T . vincentii depended on both polyamines and lecithin for growth . Specific requirements for purines and/or pyrimidines were detected, and these requirements could be used to distinguish Haemophilus-Actinobacillus group organisms . Some strains of P . gingivalis grew without vitamin K, while others were not satisfied by menadione but required its precursor 1,4-dihydroxy-2-naphthoic acid . Protoporphyrin IX or hemin equally satisfied the porphyrin requirements of P . gingivalis and Bacteroides forsythus, whereas ferrous sulfate was more efficiently used as a source of iron than was hemin . The cellular cohesiveness of P . gingivalis increased with high concentrations of hemin in the growth medium . Prevotella intermedia, B . forsythus, and several strains of P . gingivalis were more fastidious and required a protein or serum supplement to grow in medium OMIZ-W1. Del Med J, 1992 Sep, 64(9), 547 - 9 Implementation of the Haemophilus B vaccine for infants by family physicians; Funk WB et al.; This study surveyed the members of the Department of Family Practice in a community hospital regarding the implementation of the newly recommended immunization protocol using Haemophilus Influenzae B Vaccine (HbOC) for infants at 2, 4, and 6 months of age . The purpose was to assess the ability of the physicians to alter their established practices in a timely fashion . The results show that initially 38/66 (58 percent) of the family physicians who care for infants and children were using the new vaccine already (eight to 10 weeks after FDA release) . An additional 11 (17 percent) had begun using the vaccine by a second interview four weeks later . Another six (nine percent) responded to a call by a family practice resident . The remaining 16 percent preferred to await governmental regulations or did not respond to interview . Despite uncertain communications to family physicians in this community, the majority were aware of and adapted readily to new immunization recommendations . Prompt notification of all physicians regarding important new vaccine protocols can have a significant impact on the health of infants and children. Int J STD AIDS, 1992 Sep-Oct, 3(5), 319 - 23 Pathophysiological concept of Haemophilus ducreyi infection (chancroid) Abeck D, Johnson AP. Our knowledge concerning the pathogenesis of infection due to Haemophilus ducreyi is incomplete . In order to produce disease, H . ducreyi must presumably penetrate the skin of the external genitalia, colonize subcutaneous tissues, then produce tissue damage which results in ulcer formation . Penetration of the normal skin most likely occurs via minor abrasions . Adherence of H . ducreyi to different cell lines in vitro has been described, and might be mediated by adhesions such as pili or haemagglutinins . In addition, binding to extracellular matrix proteins has also been reported . Extracellular tissue-degrading enzymes were absent from broth culture supernatants of H . ducreyi . Such supernatants also failed to produce cytopathic effects with established or primary cell lines . Both live and heat-killed H . ducreyi organisms were able to produce lesions in a rabbit or a mouse model, although ulcer formation was dependent on viable H . ducreyi organisms in a recently introduced temperature-dependent rabbit model . With an excessive supply of iron, a more prolonged localized inflammatory disease effect was observed . Results derived from a subcutaneous chamber model demonstrated considerable changes in the expression of outer membrane proteins combined with antibody modulation during in vivo growth of H . ducreyi . These might be important factors for maintenance of infection in the human host particularly as these changes also occur in humans . Despite an increased knowledge of the pathogenesis of chancroid, important questions such as growth requirements, bubo-formation, role of cell-mediated immunity and ulcer formation are still unanswered . The application of molecular biological techniques in order to study these problems will be helpful. APMIS, 1992 Sep, 100(9), 856 - 60 Killing curve activity of ciprofloxacin is comparable to synergistic effect of beta-lactam-tobramycin combinations against Haemophilus species endocarditis strains; Westh H et al.; Nine Haemophilus species strains, all beta-lactamase negative, isolated from patients with endocarditis were tested in killing curve experiments . Antibiotics used were penicillin, amoxicillin, aztreonam alone and in combination with tobramycin, as well as ciprofloxacin alone . Synergism between beta-lactams and tobramycin with reduction of colony counts to zero was seen after 24 h for H . influenzae, H . parainfluenzae and H . segnis strains . Ciprofloxacin was as effective as beta-lactam-tobramycin combinations . The H . aphrophilus strain was not killed as effectively as other strains by any of the antibiotics. J Dent Res, 1992 Sep, 71(9), 1561 - 8 Identification and analysis of the gap region in the 23S ribosomal RNA from Actinobacillus actinomycetemcomitans; Haraszthy VI et al.; Actinobacillus actinomycetemcomitans is a Gram-negative coccobacillus which can cause certain severe extra-oral infections as well as forms of human periodontal disease such as localized juvenile periodontitis . In contrast to many prokaryotic and eukaryotic species which exhibit an intact 23S ribosomal RNA (rRNA) molecule, examination of six A . actinomycetemcomitans strains--including three serogroup representative strains and two strains from non-human primates--revealed that this micro-organism does not produce an intact 23S ribosomal RNA (rRNA) molecule but, rather, two smaller forms of 1.8 kb and 1.2 kb designated as 23S alpha and 23S beta fragments . On the other hand, 14 other strains of Actinobacillus, Haemophilus, and Pasteurella species demonstrated intact 23S rRNA . The sequence of the region of the 23S rRNA gene in A . actinomycetemcomitans strain ATCC 43718 containing the cleavage site was determined by dideoxynucleotide sequencing, while the location of the 3' and 5' termini of the 23S alpha and 23S beta fragments was resolved by S1 nuclease mapping and cDNA primer-extension . A deletion of 112 bases was noted in comparisons of base sequences from A . actinomycetemcomitans rRNA and rDNA . The DNA intervening sequence was localized to nucleotide 1180 of the Escherichia coli 23S rRNA map . While the primary structure of the gap region showed little homology with the gap regions described in other organisms, the secondary structure was similar to that previously described in the parasitic helminth Schistosoma japonicum . Restriction enzyme and nucleotide sequence analysis of the gap region in eight other A . actinomycetemcomitans strains showed it to be highly conserved. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi, 1992 Sep-Oct, 33(5), 383 - 7 {Haemophilus influenzae cellulitis of the hand: report of one case}; Ko FY et al.; Cellulitis of extremities due to Haemophilus influenzae is rare in children . Only 60 cases of Haemophilus influenzae cellulitis of the extremities have been reported . It usually affects young children between the ages of six and 24 months . The lesion often presents with a red-to-bluish-purple discoloration overlying the involved area . High fever and leukocytosis are commonly found . Culture of needle aspirate and blood with appropriate media is necessary for diagnosis . Early diagnosis is especially important because of associated bacteremia and the subsequent possibility of life-threatening complications such as meningitis . We reported a 8-month-old female infant with Haemophilus influenzae type b cellulitis over the right hand . She was admitted due to high fever and painful swelling of the right hand . Edematous right hand with dusky erythematous skin over the dorsum and swelling of the palm with limitation of range of motion were noted on admission . Smear of needle aspirate revealed gram negative bacilli and beta-lactamase(-) Haemophilus influenzae type b was cultivated in the blood culture . She was successfully treated with ampicillin and discharged with stable condition. Microb Pathog, 1992 Sep, 13(3), 203 - 17 The role of Haemophilus ducreyi bacteria, cytotoxin, endotoxin and antibodies in animal models for study of chancroid; Lagergard T; Haemophilus ducreyi cytotoxin-positive and -negative strains as well as bacterial sonicates and lipooligosaccharides (LOS) from such strains were evaluated for the capacity to produce dermonecrotic lesions, especially ulcers, after intradermal injections to rabbits and to different mouse strains, including nude mice . Dermonecrotic lesions of the ulcerous type were observed within 4 days and they were developed in both rabbits and mice with about 10(7) colony forming units (cfu) of H . ducreyi . Viable bacteria were isolated from the lesions up to 9 days after inoculation . All lesions healed spontaneously within 2-3 weeks . Bacterial sonicate (heated and unheated) and LOS preparations caused mainly abscess formation in rabbits, while in mice, a superficial, haemorrhagic ulceration was observed . To obtain ulceration at all injection sites, about 200 micrograms of LOS was required . Histological examination of acute, dermonecrotic lesions caused by viable bacteria showed deep necrosis, infiltrate of inflammatory cells, especially granulocytes and dilatation of blood vessels . The same type of inflammatory cells as seen in lesions caused by bacteria, were involved in the mouse lesions caused by bacterial sonicate and LOS preparations . The results indicate that LOS/endotoxin, probably in combination with other bacterial polysaccharides, can play a role in ulceration caused by H . ducreyi in animals; however, a relatively high amount of LOS preparation was necessary to cause dermal ulceration at all injection sites in the mouse model . The development of ulcers correlated with the endotoxin activity in bacterial sonicate and in LOS preparations . The model may therefore be useful to study the role of LOS components in development of ulceration . There was no significant difference in lesions caused by cytotoxin producing, respectively, non-producing H . ducreyi strains and cell-free preparations from such strains . The bacterial sonicates, cytotoxic for human cell lines, failed to kill animal cell lines, indicating that animal models do not adequately reflect the cytotoxin activity in experimental H . ducreyi infection . Antibodies to H . ducreyi sonicate and LOS, tested by means of ELISA, were found in pre-immune sera from both rabbits and mice . There was a significant antibody response to homologous cell sonicate and LOS, after primary and secondary infections with bacteria . Still, there was no clear difference between primary and secondary lesions in animals . Since animal lesions are mainly due to endotoxin activity, this may indicate that antibodies are of minor importance for protection in animal models. Microb Pathog, 1992 Sep, 13(3), 191 - 202 Effect of Haemophilus somnus on phagocytosis and hydrogen peroxide production by bovine polymorphonuclear leukocytes; Pfeifer CG et al.; The interactions between bovine polymorphonuclear leukocytes (PMNs) and the bacterium Haemophilus somnus are known to be complex . In this paper, we evaluated the effect of H . somnus on PMN function using a flow cytometric (FC) technique that simultaneously determined the extent of phagocytosis and hydrogen peroxide production by PMNs, as well as using conventional techniques, such as the nitroblue tetrazolium (NBT) and chemiluminescence assays, to analyse the PMN respiratory burst . Results from the FC and chemiluminescence assays demonstrated that in vitro exposure of PMNs to logarithmically growing H . somnus reduced the respiratory burst of PMNs obtained from healthy calves . However, this reduction was not detected by the NBT assay . A decrease in phagocytosis by PMNs could also be shown using the FC assay . In addition, PMNs from calves with acute Hemophilosis (i.e . exposed to H . somnus in vivo) showed reduced activity when compared to PMNs from healthy calves . These in vitro and in vivo observations indicate that the modulation of bovine PMN function by H . somnus may contribute significantly towards the pathogenesis of the disease. Electrophoresis, 1992 Sep-Oct, 13(9-10), 743 - 6 Two-dimensional electrophoresis analysis of human serum proteins during the acute-phase response; Bini L et al.; The serum of patients with meningitis, due to infection by Haemophilus influenzae type b, was analyzed . Several known acute-phase proteins were separated by two-dimensional electrophoresis and estimated quantitatively . In addition, hitherto undescribed reactants were recognized . Gels were calibrated and relevant spots related to master spot numbers in the human serum protein database. J Bacteriol, 1992 Aug, 174(16), 5442 - 9 Use of electroporation to construct isogenic mutants of Haemophilus ducreyi; Hansen EJ et al.; Little is known about the genetics of Haemophilus ducreyi, the etiologic agent of chancroid . To develop a method for constructing isogenic mutants of this organism that could be utilized in pathogenesis-related studies, electroporation techniques were evaluated as a means of introducing DNA into this organism . Electroporation of the plasmid shuttle vector pLS88 into H . ducreyi yielded approximately 10(6) antibiotic-resistant transformants per microgram of plasmid DNA . Studies of the feasibility of moving mutated genes into H . ducreyi were initiated by using NotI linker insertion and mini-Tn10kan mutagenesis techniques to introduce insertion mutations into cloned H . ducreyi genes encoding cell envelope antigens . In the former case, a gene encoding chloramphenicol acetyltransferase was then inserted into the NotI linker site created in the cloned H . ducreyi gene . The recombinant Escherichia coli strains containing these mutated plasmids no longer expressed the homologous H . ducreyi cell envelope antigens, as evidenced by their lack of reactivity with monoclonal antibody probes for these H . ducreyi proteins . Subsequent electroporation of both circular and linearized forms of plasmids carrying these mutated H . ducreyi genes into the homologous wild-type strain of H . ducreyi yielded antibiotic-resistant transformants which also lacked reactivity with the cell envelope antigen-specific monoclonal antibodies . Southern blot analysis confirmed that homologous recombination had occurred in these monoclonal antibody-unreactive transformants, resulting in the replacement of the wild-type allele with the mutated allele . Allelic exchange was most efficient when linear DNA molecules were used for electroporation . These results indicate that electroporation methods can be utilized to construct isogenic mutants of H . ducreyi. J Pediatr, 1992 Aug, 121(2), 187 - 94 Differences in the immunogenicity of three Haemophilus influenzae type b conjugate vaccines in infants; Granoff DM et al.; OBJECTIVE: To compare the immunogenicity of three Haemophilus influenzae type b (Hib) conjugate vaccines in infants residing in different geographic areas . DESIGN: A multicenter, randomized immunogenicity trial with sera assayed in one laboratory without knowledge of vaccine brand status . In Minneapolis and Dallas, infants were vaccinated at 2, 4, and 6 months of age; in St . Louis, infants were vaccinated at 2 and 4 months of age . SUBJECTS: A convenience sample of 458 infants recruited largely from private pediatric practices . MEASUREMENTS AND RESULTS: At each of the study sites, the respective trends between the anticapsular antibody responses of the infants assigned to the different conjugate vaccine groups were similar . After one or two doses, Hib polysaccharide conjugated to outer membrane protein complex of Neisseria meningitidis (PRP-OMP) was more immunogenic than Hib polysaccharide-tetanus toxoid conjugate (PRP-T), or Hib oligomers conjugated to the mutant diphtheria toxin CRM197 (HbOC) (p less than 0.001) . After two doses, PRP-T was more immunogenic than HbOC (p less than or equal to 0.001) . After three doses there was no significant difference in the geometric mean antibody concentrations of the three groups, and 88% to 97% of the infants had greater than 1.0 microgram/ml of antibody . The HbOC vaccine elicited a 10-fold lower antibody response after two doses (0.45 micrograms/ml vs 5.9 micrograms/ml) and a threefold lower antibody response after three doses (6.3 micrograms/ml vs 22.9 micrograms/ml) than observed by us previously with a prelicensure lot of this vaccine (p less than 0.001) . Because of these low responses, the infants in St . Louis who received two doses of HbOC were revaccinated with unconjugated PRP at a mean age of 8.9 months . This group was immunologically primed, as evidenced by a 10-fold increase in geometric mean antibody concentration after vaccination at an age when unprimed infants do not normally respond to this vaccine . CONCLUSIONS: In infants in three geographic regions, PRP-OMP elicited earlier acquisition of serum antibody than the other two conjugate vaccines; however, after three doses the antibody concentrations of the three groups were not significantly different . The reason for the markedly lower immunogenicity of HbOC vaccine than reported previously is unknown. Infect Immun, 1992 Aug, 60(8), 3448 - 51 Elevated body temperature restricts growth of Haemophilus influenzae type b during experimental meningitis; O'Reilly T et al.; Elevation of the environmental temperature appeared to counteract the temperature-depressing effects of urethane anesthetic and allowed rabbits intracisternally infected with Haemophilus influenzae type b to mimic the development of a fever following infection . Elevated core body temperature (greater than 39 degrees C) was associated with an inhibition of the growth of H . influenzae in cerebrospinal fluid (CSF) during the first 12 h postinfection, whereas bacterial growth was essentially unrestricted in rabbits with reduced (approximately 37 degrees C) body temperature . Bacterial densities 24 h postinfection were different, hyperthermic animals having log 6.0 +/- 0.4 CFU/ml of CSF and hypothermic rabbits having log 8.2 +/- 0.8 CFU/ml of CSF (P less than 0.05, Wilcoxon rank sum test) . However, the growth of this bacterium in vitro, in either pooled rabbit CSF or brain heart infusion broth, was not inhibited at 39 degrees C . These results suggest that elevated body temperature associated with the development of fever during meningitis may be associated with restriction of the growth of H . influenzae in vivo but that this effect is apparently not due to an innate inability of the bacterium to grow at elevated temperatures. Infect Immun, 1992 Aug, 60(8), 3423 - 7 Antibodies to lipooligosaccharide of a Brazilian purpuric fever isolate of Haemophilus influenzae biogroup aegyptius lack bactericidal and protective activity; Peters VB et al.; The immunological basis for protection against Brazilian purpuric fever (BPF), a fulminant infection of young children associated with bacteremia with Haemophilus influenzae biogroup aegyptius, is unknown . Candidate antigens to which protective antibodies may be directed include cell surface proteins and lipooligosaccharide (LOS) . We studied the activity of antisera to LOS purified from a BPF H . influenzae biogroup aegyptius isolate . Anti-LOS antisera contained anti-LOS antibody by enzyme immunoassay and immunoblot and no detectable anti-outer membrane protein antibodies by immunoblot . Anti-LOS antisera had minimal bactericidal activity and were not protective against the homologous strain in an infant rat model of bacteremia . Antiserum to whole bacterial cells had a titer of anti-LOS antibody similar to that of anti-LOS antisera and was bactericidal and protective . Removal of anti-LOS antibodies from anti-whole cell antiserum by affinity chromatography did not result in a loss of bactericidal activity . Serum from a normal adult contained anti-LOS antibodies and had bactericidal activity . However, anti-LOS antibodies purified from this serum did not have detectable bactericidal activity . These studies suggest that anti-LOS antibodies produced in rats are not bactericidal and do not contribute to protection against experimental bacteremia with BPF strains of H . influenzae biogroup aegyptius. J Med Microbiol, 1992 Aug, 37(2), 133 - 40 Effect of haemin limitation on the cytochrome complement and glucose metabolism of non-typable Haemophilus influenzae; O'Reilly T et al.; Haemophilus influenzae grown to exponential phase or stationary phase in medium with a low initial concentration of haemin (0.25 microgram/ml) was virtually devoid of cytochromes . Compared with bacteria grown in the presence of excess haemin (10 micrograms/ml), the haemin-limited organisms failed to respire formate and succinate and, generally, the respiratory rates with other substrates were reduced . However, growth rates were not affected by the haemin supply . Haemin-limited growth was associated with a reduced efficiency of glucose utilisation, in terms of glucose growth yields, and affected the net levels of excreted organic acids . Haemin limitation resulted in reduced acetate and increased succinate accumulation in the culture medium and the novel presence of D-lactate . These results indicate that, in contrast to the phenotype expressed in vitro during conventional cultivation of H . influenzae, the haemin-limited phenotype, which may be expressed in vivo, is characterised by a lack of cytochromes and a shift towards a more anaerobic type of metabolism. Mol Cell Probes, 1992 Aug, 6(4), 299 - 304 Detection of Pseudomonas aeruginosa in sputum from cystic fibrosis patients by the polymerase chain reaction; McIntosh I et al.; A DNA amplification procedure using heat stable Taq polymerase and the polymerase chain reaction is described for the detection of Pseudomonas aeruginosa in specimens from cystic fibrosis patients . A set of primers was selected on the basis of the nucleotide sequence of the algD gene encoding GDP mannose dehydrogenase, a major enzyme in the biosynthesis of alginate by P . aeruginosa . Using this set of primers in conjunction with the polymerase chain reaction, P . aeruginosa could be specifically detected, with a sensitivity approximating 10 bacteria, in sputum harbouring large numbers of other respiratory pathogens, including Staphylococcus aureus and Haemophilus influenzae . These results suggest that amplification of specific sequences within the algD gene by the polymerase chain reaction may provide a highly sensitive and specific tool for the detection of P . aeruginosa in the early stages of pulmonary colonization. Am J Infect Control, 1992 Aug, 20(4), 192 - 7 Relative frequency of nosocomial pathogens at a university hospital during the decade 1980 to 1989; Weber DJ et al.; BACKGROUND: We compared the relative frequency of pathogens isolated from 1985 to 1989 (N = 4358) with those isolated from 1980 to 1984 (N = 5290) in a university hospital to determine trends in the relative importance of pathogens causing nosocomial infection . METHODS: Our study was based on surveillance data prospectively obtained between 1980 and 1989 from a 600-bed university hospital . Statistically significant trends occurring from 1980 to 1984 to 1985 to 1989 were determined by chi 2 tests with Bonferroni corrections (i.e., p less than {0.05/17}) . RESULTS: Overall an increased frequency of isolation occurred for Candida and other yeasts and for Haemophilus species . A decreased frequency was noted for Proteus species, non-Bacteroides anaerobes, and Serratia species . Comparison of 1985 to 1989 with 1980 to 1984 revealed that the most significant change in nosocomial pathogens was the marked increase in infections with yeast, principally Candida species . Candida and other yeast infections increased 40%, from 7.6% (rank, 5) to 10.6% (rank, 3) of all pathogens isolated . Increases, which occurred in urine, blood, and wound isolates, were especially marked among surgical patients . In addition, a significant increase was noted among blood isolates in the isolation of yeast other than Candida albicans . CONCLUSIONS: We conclude that Candida and other yeasts are being isolated increasingly as causative agents of nosocomial infection. Pediatr Infect Dis J, 1992 Aug, 11(8), 610 - 3 Immunization with oligosaccharide conjugate Haemophilus influenzae type b (HbOC) vaccine on a large health maintenance organization population: extended follow-up and impact on Haemophilus influenzae disease epidemiology . The Kaiser Permanente Pediatric Vaccine Study Group; Black SB et al.; Between February, 1988, and June, 1990, the safety, immunogenicity and efficacy of the HbOC (oligosaccharide conjugate Haemophilus influenza type b) vaccine was evaluated in a prelicensure trial performed in a study population of 61,080 children within the Northern California Kaiser Permanente Medical Care Program . In this evaluation the HbOC vaccine was found to be safe, immunogenic and efficacious in infancy . Since licensure an estimated 162,000 additional doses of HbOC vaccine have been given to 75,000 additional children . In addition to reporting on extended follow-up of this population, this publication reports on the impact of immunizing a high proportion of the Northern California Kaiser Permanente Medical Care Program population in infancy and early childhood on the epidemiology of invasive disease caused by H . influenzae type b (Hib) and invasive disease caused by non-type b H . influenzae . As of January 31, 1992, six cases of Hib invasive disease have been identified in vaccinated children . Of these five occurred in children who had received only one dose of vaccine in infancy . One case of Hib meningitis occurred in a 3 1/2-year-old child who had received doses of HbOC at 2, 4 and 6 months of age but no further doses of any Hib vaccines . During 1991 a total of three cases of invasive disease caused by Hib were observed in children younger than 18 months of age within the Northern California Kaiser Permanente Medical Care Program . This represents a 94% reduction in disease incidence in this age group from that observed in the years 1984 to 1987.(ABSTRACT TRUNCATED AT 250 WORDS) Pediatr Emerg Care, 1992 Aug, 8(4), 206 - 8 Uvulitis in three children: etiology and respiratory distress; Aquino V et al.; Uvulitis is an uncommonly reported disorder with the potential for significant morbidity . We describe three cases of uvulitis seen within a six month period in our emergency department . In two cases with respiratory distress, but without epiglottitis, Haemophilus influenzae was isolated from throat or blood cultures . The third case was associated with group A streptococcus tonsillitis and no respiratory compromise . Atypical presentations of upper airway infection with H . influenzae may be increasingly common. Pediatr Infect Dis J, 1992 Aug, 11(8 Suppl), S7 - 11 Ten-year review of otitis media pathogens; Bluestone CD et al.; Data collected from 1980 to 1989 by investigators at the Pittsburgh Otitis Media Research Center were examined to detect changes over time in the prevalence of bacteria isolated from middle ear effusions in patients with otitis media . The organisms isolated most commonly from the 7396 effusions cultured at the center were Streptococcus pneumoniae and Haemophilus influenzae . S . pneumoniae predominated in the subgroup of patients with acute otitis media, whereas H . influenzae was isolated most frequently from patients with otitis media with effusion . The most notable changes to occur during the 10-year period were a statistically significant increase in the prevalence of S . pneumoniae in patients with acute otitis media and a progressive rise in the percentage of beta-lactamase-producing strains of H . influenzae and Moraxella (Branhamella) catarrhalis . The latter finding suggests the need for therapeutic alternatives to amoxicillin, which is not active against beta-lactamase-producing organisms, when these organisms are suspected or cultured from the middle ear. J Clin Microbiol, 1992 Aug, 30(8), 2108 - 12 Isolation and characterization of a newly identified Haemophilus species from cats: "Haemophilus felis"; Inzana TJ et al.; A gram-negative coccobacillus was isolated from the lower respiratory tract of a cat with chronic obstructive pulmonary disease . The isolate required CO2 and V factor for growth and was initially identified as Haemophilus paraphrophilus on the basis of its nutritional requirements, colony morphology, and some biochemical tests . Because of the host specificity of Haemophilus species and discrepancies in catalase, oxidase, and hemolytic activities, additional testing was done . Extensive biochemical testing, G+C content, and DNA reassociation studies indicated that the organism was distinct from other Haemophilus species . Therefore, the organism was identified as a previously unrecognized Haemophilus species and was tentatively named "Haemophilus felis." Bacteria identical to the original isolate were isolated from the nasopharynxes of 6 of 28 apparently normal cats, indicating that H . felis or H . felis-like organisms may be common members of the feline upper respiratory tract flora. J Clin Microbiol, 1992 Aug, 30(8), 2033 - 7 Haemophilus influenzae ATCC 49766, an alternative quality control strain for monitoring broth microdilution susceptibility tests with selected beta-lactams; Barry AL et al.; A beta-lactamase-negative, ampicillin-resistant strain of Haemophilus influenzae is currently used for quality control of broth microdilution tests performed with Haemophilus test medium (HTM) . Studies with eight lots of HTM broth documented the fact that MIC limits for some antimicrobial agents are unrealistically stringent; i.e., only three of eight lots of HTM broth were satisfactory for testing cefaclor . An alternative, ampicillin-susceptible strain of H . influenzae (ATCC 49766) was found to provide much more reproducible results with five problematic drugs (cefaclor, cefuroxime, cefamandole, loracarbef, and cefonicid) . Multilaboratory studies defined MIC control limits for both control strains tested against 12 antimicrobial agents. J Clin Microbiol, 1992 Aug, 30(8), 2029 - 32 Development of revised quality control limits for disk diffusion susceptibility tests of selected cephem antibiotics with Haemophilus influenzae and description of a new control strain; Jorgensen JH et al.; Inconsistent quality control results in disk diffusion testing of cefaclor, cefamandole, cefonicid, and cefuroxime with Haemophilus influenzae ATCC 49247 and Haemophilus test medium (HTM) prompted a search for an alternative control strain that would provide more reliable results . A five-laboratory study was conducted to evaluate two candidate H . influenzae strains as possible alternatives to the aforementioned strain . Repetitive testing of the candidate strains and H . influenzae ATCC 49247 over several days with a total of six different lots of HTM documented consistent performance of the two candidate strains and confirmed inconsistent results for some of the antibiotics with H . influenzae ATCC 49247 . In particular, certain lots of HTM failed to yield cefaclor and cefamandole zone sizes within the quality control range advocated by the National Committee for Clinical Laboratory Standards . Because of the greater consistency offered by the new strains, one was selected (now designated H . influenzae ATCC 49766) to be recommended for routine quality control testing of cefaclor, cefamandole, cefonicid, cefuroxime, and the related carbacephem loracarbef . The new control strain and zone size ranges proposed here have been approved by the National Committee for Clinical Laboratory Standards in place of the previously recommended strain and zone size limits for testing of these five cephem antibiotics. J Clin Microbiol, 1992 Aug, 30(8), 2019 - 24 Standardization of an enzyme immunoassay for human antibody to Haemophilus ducreyi; Desjardins M et al.; We standardized a serologic enzyme immunoassay (EIA) for human immunoglobulin G and M antibodies against Haemophilus ducreyi . We evaluated the performance of this test with respect to the time from acute chancroid and coinfection with human immunodeficiency virus (HIV) . Antibody to a crude, soluble bacterial antigen of one H . ducreyi strain was detected in a panel of serum samples from clinically and microbiologically confirmed cases of chancroid and from controls . Test interpretation was standardized for optimal sensitivity and specificity . Performance of the EIA was enhanced in the period of early convalescence from acute primary chancroid and was not diminished in the presence of HIV coinfection . The EIA performed adequately as a serologic screening test for field evaluation and epidemiologic application in conjunction with sexually transmitted disease and HIV detection and control efforts. J Clin Microbiol, 1992 Aug, 30(8), 1917 - 21 Laboratory and clinical evaluations of media for the primary isolation of Haemophilus species; Rennie R et al.; There has not previously been an objective comparison of medium formulations for the primary isolation of Haemophilus species . This study was undertaken to evaluate the components required for the optimal growth of large, easily identifiable colonies of these bacteria . We compared six medium bases and seven supplements for their ability to support the growth of 86 strains of Haemophilus influenzae and 17 strains of other species of Haemophilus . By using a growth index that combines colony size and the dilution factor, a formulation of GC agar base with 1% yeast autolysate and 5% sheep blood (chocolated) promoted the growth of large, easily recognizable colonies of H . influenzae and other Haemophilus species . This medium was designated GCYSB . The addition of hematin to supplements that supplied NAD (or factor V) to the medium was inhibitory to the growth of all of the Haemophilus species tested . In a clinical comparison of GCYSB with routinely used chocolate agar medium in two laboratories for the primary isolation of Haemophilus species, overall GCYSB promoted better growth of 124 strains of H . influenzae and H . parainfluenzae . GCYSB is easy to prepare and inexpensive compared with the ease of preparation and expense of other Haemophilus isolation media. Health Visit . 1992 Aug;65(8):268. HIB . Assessing information needs; McGuire C; Planning the launch of the new Haemophilus influenzae b vaccine in October of this year has challenged health educators involved with child immunisation, writes Christine McGuire of the Health Education Authority (HEA) . Here she outlines the findings from initial research commissioned to explore parental and professional information needs. Health Visit, 1992 Aug, 65(8), 264 - 5 Primary prevention of haemophilus influenzae type b; Hodgson S; Routine immunisation of infants against Haemophilus influenzae type b (Hib) has the potential to prevent up to 1200 cases of serious infection and 60 deaths every year in the United Kingdom . Sara Hodgson reports the findings of a study in the Oxford region to determine the safety and immunogenicity of the Hib conjugate vaccine PRP-T when given to British infants in concurrence with primary immunisations, according to the accelerated schedule of two, three and four months of age. Jpn J Antibiot, 1992 Aug, 45(8), 980 - 9 {Antimicrobial activities of major oral antibacterial agents against clinically isolated microbial strains from outpatients with respiratory tract infection}; Deguchi K et al.; Minimum inhibitory concentrations (MICs) were determined for major oral antibacterial agents for clinically isolated microbial strains from materials collected from outpatients with respiratory tract infections in 1988, 1989 and 1990, and the following conclusions were obtained . 1 . Methicillin-resistant Staphylococcus aureus (MRSA) appeared to be responsible for community-acquired respiratory tract infections, but there also was a tendency showing that MRSA increased year by year . 2 . A tendency was observed indicating that benzylpenicillin (PCG)-insensitive Streptococcus pneumoniae (PISP) increased year by year . 3 . Beta-lactamase-producing strains of Haemophilus influenzae were observed in a certain ratio, and also those of Branhamella catarrhalis were found in high ratios . 4 . A tendency of increasing resistance of Klebsiella pneumoniae to new quinolones was observed . 5 . It is of a great importance to evaluate methods of selecting primary choice antibiotic agents since increasing numbers of new oral antibacterial agents are becoming rapidly available. Eur J Clin Microbiol Infect Dis, 1992 Aug, 11(8), 748 - 51 In vitro susceptibility of Haemophilus influenzae to cefaclor, cefixime, cefetamet and loracarbef; Williams JD et al.; The susceptibility of 2,212 Haemophilus influenzae isolates cultured in UK clinical laboratories in 1991 was determined for four orally-administered beta-lactam drugs . These isolates included 1,893 ampicillin-susceptible, 191 beta-lactamase-positive and 128 ampicillin-resistant, beta-lactamase-negative Haemophilus influenzae . While 150 (6.8%) isolates were resistant to cefaclor (MIC > or = 16 mg/l) and 85 (3.8%) to loracarbef, all were inhibited by < or = 2 mg/l cefetamet and < or = 1 mg/l cefixime and were therefore susceptible to these agents . Ranges and modes of inhibition zone diameters and MICs indicated that the susceptibility of a variable proportion of the 191 beta-lactamase-positive isolates to cefaclor, loracarbef and cefetamet was reduced compared with the fully susceptible population . In contrast, a major reduction in susceptibility to all four antimicrobial agents was seen among the 128 ampicillin-resistant (MIC 1-64 mg/l) beta-lactamase-negative isolates such that these accounted for 53% and 67% of the total number of organisms resistant to cefaclor and loracarbef respectively . In addition, 23 of 25 isolates inhibited only by > or = 1 mg/l cefetamet and all eight inhibited only by > or = 0.5 mg/l cefixime showed this type of resistance to ampicillin . Results indicate the importance of detecting non-beta-lactamase-mediated resistance to ampicillin and any concomitant diminished susceptibility to other beta-lactam drugs. Antimicrob Agents Chemother, 1992 Aug, 36(8), 1639 - 43 Correlation between in vitro antimicrobial susceptibilities and beta-lactamase plasmid contents of isolates of Haemophilus ducreyi from the United States; Motley M et al.; We determined the susceptibilities of 94 strains of Haemophilus ducreyi isolated in various municipalities in the United States between 1982 and 1989 to the following antimicrobial agents: amoxicillin-clavulanic acid, ceftriaxone, erythromycin, azithromycin, ciprofloxacin, ofloxacin, trimethoprim, and spectinomycin . Ceftriaxone (MIC, less than or equal to 0.008 micrograms/ml), azithromycin (MIC, less than or equal to 0.125 micrograms/ml), erythromycin (MIC, less than or equal to 0.125 micrograms/ml), ciprofloxacin (MIC, less than or equal to 0.25 micrograms/ml), and ofloxacin (MIC, less than or equal to 0.25 micrograms/ml) were highly active against all isolates . Amoxicillin-clavulanic acid (MICs, 0.25 to 8.0 micrograms/ml), trimethoprim (MICs, 0.06 to 16.0 micrograms/ml), and spectinomycin (MICs, 2.0 to greater than or equal to 32.0 micrograms/ml) were less active against these isolates . Isolates possessing the 5.7-MDa beta-lactamase plasmid were less susceptible to erythromycin, trimethoprim, and spectinomycin than were isolates possessing the 3.2-MDa beta-lactamase plasmid . The susceptibilities of plasmidless isolates to erythromycin, trimethoprim, and spectinomycin were distributed bimodally; the median MIC for the more susceptible plasmidless isolates corresponded to that for isolates with the 3.2-MDa plasmid, and the median MIC for the less susceptible plasmidless isolates corresponded to that for isolates with the 5.7-MDa plasmid . Thus, plasmid profiles may be valuable markers for geographical variations in antimicrobial susceptibilities of H . ducreyi strains that may indicate the relative efficacy of regimens for the treatment of chancroid . Of the regimens recommended by the U.S . Public Health Service for the treatment of chancroid, our results support the use of erythromycin, ceftriaxone, and ciprofloxacin, and perhaps ofloxacin, but suggest that amoxicillin-clavulanic acid and sulfamethoxazole-trimethoprim should be used with caution. An Esp Pediatr, 1992 Aug, 37(2), 126 - 9 {Acute otitis media in childhood . Clinical and microbiological study of 50 cases}; Del Castillo Martin F et al.; Fifty cases of acute otitis media effusion (AOME) in children less than 14 years of age are reported . The largest age group consisted of children less than 22 months of age (22 cases) . Otolgia or irritability (80%) and fever (66%) were the most common symptoms . Tympanocentesis of the middle-ear effusion was performed in all of the cases . Haemophilus influenzae was recovered in 13 patients (26%), S . pneumoniae in 12 (24%), S . pyogenes in 4 (8%), P . aeruginosa in 2 (4%), anaerobic bacteria in 2 (4%) and mixed cultures in 4 children; 2 cases of H . influenzae and S . pneumoniae, 1 case of S . pneumoniae and E . coli, and 1 case of E . coli and P . aeruginosa . There were no cases of M . catarrhalis or S . aureus . We conclude that H . influenzae and S . pneumoniae are the most frequent pathogens (60% of all patients and 81% of the positive cultures). J Pediatr Surg, 1992 Aug, 27(8), 1045 - 7; discussion 1048 Response to Haemophilus influenzae type B conjugate vaccine in children undergoing splenectomy; Ambrosino DM et al.; Asplenic children are at increased risk for serious infection with polysaccharide encapsulated bacteria including Haemophilus influenzae type b (HIB), Streptococcus pneumoniae, and Neisseria meningitidis . Immunization with polysaccharide vaccines is recommended for children undergoing splenectomy . In 1987 a new more immunogenic HIB vaccine was licensed in the US to replace the pure HIB polysaccharide vaccine that was licensed in 1985 . This polysaccharide-conjugate vaccine consists of the HIB polysaccharide linked to a protein carrier, diphtheria toxoid . Therefore, we evaluated the immune response of children undergoing splenectomy to HIB-conjugate vaccine . Thirteen children (7 with Hodgkin's disease, 4 with idiopathic thrombocytopenia, 2 with hereditary spherocytosis) aged 3 to 19 years were immunized with HIB-conjugate vaccine prior to splenectomy and serum was obtained following splenectomy . In addition, 15 healthy control children aged 2 to 14 years were immunized with the pure polysaccharide HIB vaccine for comparison . The patients undergoing splenectomy who received the HIB-conjugate vaccine had a geometric mean IgG anti-HIB antibody concentration of 48,106 ng/mL versus 10,786 ng/mL for the control patients who received the pure polysaccharide vaccine (P = .01) . The presumed protective level of antibody is 1,000 ng/mL and all children were well above this concentration . Therefore, we propose that children undergoing splenectomy be immunized with an HIB-conjugate vaccine. J Chemother, 1992 Aug, 4(4), 211 - 5 Microbiological considerations of the etiological agents of lower respiratory tract infections; Pellegrino MB et al.; One hundred eight-four sputum specimens from the same number of patients with lower respiratory tract infections were examined to determine the bacterial count and the relationship between the microorganisms isolated and the presumptive pathology . The sputa were subdivided into three groups; "high probability", "low probability", and "contaminated sputa", following the criteria of the microscopic readings: sputum with more than 25 white cells and low numbers of squamous epithelial cells represents true lower respiratory tract infections (high probability); those with fewer than 25 white cells represent non-bacterial infections or non-infected sputa (low probability) while sputa with more than 25 squamous cells per field represent contaminated specimens (contaminated sputa) . Statistical analysis was carried out to correlate these data . Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae, and Streptococcus pyogenes showed significant differences in the three groups considered. J Antimicrob Chemother, 1992 Aug, 30(2), 165 - 72 Bactericidal activity of beta-lactams and amikacin against Haemophilus influenzae: effect on endotoxin release; Bingen E et al.; Ampicillin or cefotaxime, alone or in combination with amikacin, were tested at levels achievable in CSF for bactericidal activity against eight clinical isolates of Haemophilus influenzae serotype b . Endotoxin release was determined by the limulus amoebocyte lysate test and by macrophage tumour necrosis factor production for each beta-lactam antibiotic, alone and in combination with amikacin . Accelerated killing was observed when amikacin was added to ampicillin or cefotaxime; however, the additional antibiotic-induced bacterial lysis observed after the addition of amikacin to beta-lactam antibiotics was not associated with an increase in endotoxin release. J Antimicrob Chemother, 1992 Aug, 30(2), 153 - 63 A national collaborative study of resistance to antimicrobial agents in Haemophilus influenzae in Australian hospitals . The Australian Group for Antimicrobial Resistance (AGAR); Collignon PJ et al.; An Australia-wide survey of the prevalence of resistance to antimicrobial agents among Haemophilus influenzae was conducted on clinically significant isolates collected between July 1988 and September 1990 . Laboratories from the capital cities of each Australian state and territory participated . Nine hundred and seventy clinical isolates were examined for beta-lactamase production and the MICs of ampicillin, coamoxiclav, chloramphenicol, cefaclor, ceftriaxone, cefotaxime, tetracycline, rifampicin, trimethoprim, sulphamethoxazole and co-trimoxazole were determined using the NCCLS agar dilution method with Haemophilus Test Medium . A smaller number of isolates were tested against penicillin V, penicillin G, ciprofloxacin, piperacillin and erythromycin in addition . The proportion of beta-lactamase producing strains was higher among invasive strains (21.6%) than non-invasive strains (14.2%) and varies considerably between states . The highest prevalence of ampicillin resistance was found in invasive strains from Canberra (40.8%), the lowest in non-invasive strains from Adelaide (5.1%) . Paradoxically, in non-invasive strains, although beta-lactamase production was less common, resistance to other antimicrobials was commoner than in invasive strains and also varied between states. Pediatr Emerg Care, 1992 Aug, 8(4), 200 - 5 Blood culture results as determinants in the organism identification of bacterial meningitis; Coant PN et al.; The diagnosis of bacterial meningitis depends on a lumbar puncture (LP) . Sometimes, antibiotics are administered before a LP that is delayed owing to prior need for computerized tomography (CT) scan, technical problems, inability to obtain consent, or an unstable patient . We examined the accuracy of blood culture, cerebrospinal fluid (CSF) Gram's stain, and antigen detection by latex for organism identification of meningitis . All patients admitted to the Children's Hospital of Buffalo between January 1, 1984 and December 31, 1989 and having a CSF culture diagnosis of bacterial meningitis had their charts retrospectively reviewed . Patients excluded from the study were those with neural tube defects or CSF catheters, those admitted directly to the Intensive Care Nursery (ICN), those whose positive CSF cultures were determined to be a contaminant, those whose medical records were not found, or those older than 16 years . We analyzed a total of 178 patients with positive CSF cultures and the confirmed diagnosis of bacterial meningitis . Of 169 patients who had a blood culture performed, 86% had the organism responsible for meningitis recovered by this test, with the highest yield of 91% occurring in the 2.5-month to 24-month age group . Blood culture identified the bacteria in 94% of those patients with Haemophilus influenzae meningitis, and this yield increased to 100% when patients who had been pretreated with antibiotics were excluded . The combination of blood culture, CSF Gram's stain, and/or latex agglutination identified the causative bacteria in 92% of patients with meningitis . Blood culture, CSF Gram's stain, and latex agglutination are useful in identifying the organism causing pediatric meningitis.(ABSTRACT TRUNCATED AT 250 WORDS) Infect Immun, 1992 Aug, 60(8), 3244 - 52 Interaction of capsulate Haemophilus influenzae with human airway mucosa in vitro; Read RC et al.; Two pairs of isogenic capsulate and noncapsulate and one pair of capsulate fimbriate and nonfimbriate strains of Haemophilus influenzae type b were studied in an organ culture of human respiratory mucosa . Over 24 h, the numbers of recovered bacteria increased from the original inoculum size of 10(5) to 10(8) CFU/ml . Transmission electron microscopy and scanning electron microscopy showed that noncapsulate organisms caused significant epithelial damage, whereas capsulate strains did not . Association of noncapsulate bacteria with damaged epithelial cells was observed by 14 h of incubation . In contrast, capsulate organisms were associated with a dense, thick, gel-like matrix which was observed above the epithelial surface . These capsulate organisms were not seen to associate with the epithelial surface (by transmission electron microscopy), though they were occasionally seen adhering to cells by scanning electron microscopy . Fimbriate capsulate H . influenzae showed increased adherence to buccal cells compared with nonfimbriate capsulate organisms . There was also association of fimbriate capsulate bacteria with damaged organ culture epithelium in one of four experiments . It is concluded that both capsule and fimbriae affect the interaction of H . influenzae with human airway mucosa in vitro by influencing adherence to and damage of the epithelium. Mol Microbiol, 1992 Aug, 6(15), 2107 - 12 Variation in length and sequence of porin (ompP2) alleles of non-capsulate Haemophilus influenzae; Forbes KJ et al.; Length variations of Haemophilus influenzae outer membrane porin protein P2 were found at the DNA and protein levels, notably in non-capsulate strains . Protein length, measured by SDS-polyacrylamide gel electrophoresis, was found to correlate with the length of the gene, measured by polymerase chain reaction amplification, and ranged from 35-42 kDa and 970-1090 nucleotides, respectively . This represents a length variation of some 15% . The genetic location of these variations was studied by restriction enzyme mapping 10 of the non-capsulate strains revealing further polymorphisms at the DNA level . All 10 strains were distinct and differed from a type b strain . The conservation and assortment of the different restriction sites in the alleles is discussed in relation to the very great diversity previously described for this protein and of the whole genome itself in non-capsulate strains . The roles of selection, horizontal gene transfer, and transformation in generating this diversity are discussed. J Clin Invest, 1992 Aug, 90(2), 612 - 8 Differing roles for platelet-activating factor during inflammation of the lung and subarachnoid space . The special case of Streptococcus pneumoniae; Cabellos C et al.; Although well-characterized in the lung, the role of platelet-activating factor (PAF) in inflammation in the central nervous system is undefined . Using rabbit models of meningitis and pneumonia, PAF was found to induce significant blood-brain barrier permeability and brain edema at doses five times lower than those required to generate leukocyte recruitment to the subarachnoid space . Both leukocytosis and increased vascular permeability occurred in response to PAF in the lung . Antibody to the CD-18 family of leukocyte adhesion molecules inhibited leukocyte recruitment in response to PAF in the brain (greater than 80%); a similar level of inhibition in the lung required treatment with a combination of a PAF receptor antagonist (L-659,989) and anti-CD18 antibody . Treatment with L-659,989 decreased abnormal cerebrospinal fluid cytochemical values induced by intracisternal challenge with pneumococci but not Haemophilus influenzae, indicating a special role for PAF in pneumococcal disease . Antibodies directed at phosphorylcholine, a unique, shared determinant of bioactivity of PAF and pneumococcal cell wall, obviated the inflammatory potential of both agents . However, no evidence for a direct PAF-like activity of pneumococcal cell wall components was detected in vitro by bioassay using platelets or neutrophils . It is concluded that PAF can induce inflammation in the subarachnoid space . In brain, PAF effects appear to be mediated through CD-18-dependent events, while in lung, PAF effects independent of CD-18 are also evident . At both sites, PAF is of particular clinical importance during inflammation induced by pneumococci apparently due to a unique proinflammatory relationship between the pneumococcal cell wall teichoic acid and PAF. J Bacteriol, 1992 Aug, 174(15), 4960 - 6 rec-2-dependent phage recombination in Haemophilus influenzae; Kupfer DM et al.; The genetic transformation mutant Rd(DB117)rec- has a pleiotropic phenotype that includes reduced levels of phage recombination . Physical mapping experiments showed that this strain has a 78.5-kbp insertion in the rec-2 gene . The rec-2 dependence of phage recombination was reexamined to determine whether the defective phenotype in Rd(DB117)rec- was due to the simple disruption of the rec-2 gene or whether trans-acting factors from the inserted DNA were responsible . Analysis of strains with transposon insertions in the rec-2 gene showed that they were also defective for phage recombination . Therefore, the phage recombination defect was due solely to the disruption of the rec-2 gene . Strain KB6 is proficient for phage recombination but has a defect in genetic transformation resembling that of Rd(DB117)rec- . The transformation defect of KB6 could be complemented by the wild-type rec-2 gene, showing that the rec-2 contributions to genetic transformation and phage recombination were uncoupled in this strain . The rec-2-dependent phenotype of KB6 suggests that the rec-2 gene participates in genetic transformation and phage recombination in different ways. J Photochem Photobiol B, 1992 Jul 30, 14(4), 345 - 57 Ferric-ion-photosensitized damage to DNA by hydroxyl and non-hydroxyl radical mechanisms; Larson RA et al.; Iron(III) and UVA (320-400 nm) light strongly diminished the transforming activity of Haemophilus influenzae DNA in the presence of oxygen . Iron(III) alone in the absence of light had no measurable effect on the transforming activity . The chelating agent ethylenediaminetetraacetic acid (EDTA) conferred virtually complete protection, but hydroxyl radical scavengers (mannitol, methanol, ethanol, isopropanol and dimethyl sulfoxide) inhibited only a small fraction of the inactivation . Treatment of plasmid DNA (pBR322) with iron(III) results in the conversion of the covalently closed circular form of the plasmid to open circles and ultimately to the linear form . Concomitant with the alteration in the conformation of the plasmid, the ability to transform Escherichia coli was reduced . In model systems, iron(III) photoreacted with the DNA backbone causing nicking and double-strand breakage . The results are consistent with a mechanism involving a preliminary complexation of iron(III) by DNA followed by the generation of reactive free radicals other than .OH . We suggest that bound iron, or other UV-absorbing transition metal complexes, may be chromophores capable of causing DNA damage in the long-wave near-UV region. Am J Epidemiol, 1992 Jul 15, 136(2), 221 - 35 Risk factors for invasive Haemophilus influenzae type b in Los Angeles County children 18-60 months of age; Vadheim CM et al.; Potential factors that confer risk or protection for invasive Haemophilus influenzae type b disease were evaluated in Los Angeles County children 18-60 months of age by case-control methods . In this age group, 79 H . influenzae type b cases were identified by overlapping surveillance methods, and 221 random controls were selected by random digit dialing . Cases and controls were similar in sex, prior health, proportion attending day care, parental educational level, history of breast feeding, and proportion vaccinated with measles/mumps/rubella vaccine . The effect of H . influenzae type b vaccination was controlled in all analyses, and results of vaccine efficacy have been reported elsewhere . Cases were more likely to have a significant underlying medical condition, reside in home with more than six residents, have a lower yearly household income, have two or more smokers in the home, and to be black . Using conditional logistic regression models, the following were significant independent risk factors after adjusting for age, month of diagnosis, H . influenzae type b vaccine status, and the other factors: 1) more than two smokers in the house (odds ratio (OR) = 6.00; 95% confidence interval (CI) 1.49-24.06); 2) household size of more than six persons (OR for more than six vs . less than three persons = 3.71; 95% CI 1.10-12.60); and 3) black maternal race (OR for black vs . Hispanic = 3.47; 95% CI 1.41-8.53) . We conclude that exposure to smoking in the home, living in households with more than six members, and the black race are each independently associated with an increased risk for H . influenzae type b disease in Los Angeles County children and, when combined, constitute a major reason for H . influenzae type b disease occurrence. Antimicrob Agents Chemother, 1992 Jul, 36(7), 1504 - 13 Molecular basis of the non-beta-lactamase-mediated resistance to beta-lactam antibiotics in strains of Haemophilus influenzae isolated in Canada; Clairoux N et al.; A study recently conducted across Canada showed that 64 of 2,503 clinical isolates of Haemophilus influenzae were resistant to beta-lactams without production of a beta-lactamase (L . D . Tremblay, J . L'Ecuyer, P . Provencher, M . G . Bergeron, and Canadian Study Group, Can . Med . Assoc . J . 143:895-900, 1990) . The beta-lactamase-negative strains formed three distinct groups, with ampicillin MICs of 0.5 to 1, 2 to 4, and greater than or equal to 8 micrograms/ml for groups I, II, and III, respectively . We have investigated the mechanisms of resistance for eight strains originating from different infections and geographic areas . These strains were representative of groups I to III . Five strains were nontypeable, two were type B, and one was non-B . Chromosomal DNA extracted from each strain was used to transform the laboratory strain Rd . Transformants were selected on beta-lactam-containing plates and showed the same level of resistance to ampicillin as the donor strains . Differences in outer membrane proteins, porins, and lipopolysaccharide profiles on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) did not change with resistance . Functional analyses of purified porins in artificial lipid bilayer experiments did not explain resistance . Peptidoglycan synthesis was measured by incorporation of {14C}alanine into trichloroacetic acid-insoluble cell wall material in the presence of chloramphenicol . The growth rate and the rate of peptidoglycan synthesis observed for the transformants of the isogenic set did not correlate with resistance . Whole-cell labeling with 125I-penicillin revealed modifications in penicillin-binding proteins (PBPs) among the transformants . In particular, PBPs 3A and 3B (65 and 63 kDa, respectively) showed a decrease in affinity for beta-lactams in all transformants (groups I, II, and III) and correlated with an increased MIC except in the transformant of group III, which showed higher levels of resistance . Partial purification and proteolytic digestion of 125I-penicillin-labeled PBP 3B led to two types of CnBr peptide profiles on SDS-PAGE, the profiles of the transformed strains from groups I and II being different from those of the control group and group III . Finally, electron microscopy revealed a distinct cell filamentation for the group III transformants . These data clearly indicate that changes in PBPs are a common mechanism that results in a significant level of non-beta-lactamase-mediated beta-lactam resistance in H . influenzae despite serotype, origin of isolation, or geographic distribution. J Biol Chem, 1992 Jul 5, 267(19), 13434 - 9 Partial characterization of the major lipooligosaccharide from a strain of Haemophilus ducreyi, the causative agent of chancroid, a genital ulcer disease; Melaugh W et al.; The first preliminary structure of a surface lipooligosaccharide from Haemophilus ducreyi has been determined . The major oligosaccharide was released by mild acid hydrolysis and analyzed by liquid secondary ion and tandem mass spectrometry . The mass spectral data combined with composition and methylation analysis yielded the most probable structure; Gal1----4GlcNAc1----3Gal1----4Hep1----6Glc1----( Hep1----2Hep1----)3,4Hep1---- KDO, where the reducing terminal 3-deoxy-D-manno-octulosonic acid (or KDO) exists in an anhydro form . This anhydro species results from the elimination of a phosphate from C-4 of KDO during mild acid hydrolysis . The core heptose trisaccharide consists of L-glycero-D-manno-heptose, but analysis of the peracetylated sugars indicated that the 1,4-linked heptose is likely D-glycero-D-manno-heptose . The monoclonal antibody 3F11 generated against Neisseria gonorrhoeae also binds to this lipooligosaccharide and suggests that the terminal trisaccharide is Gal beta 1----4GlcNAc beta 1----3Gal beta 1----, an epitope found in the glycose moiety of the human erythrocyte glycosphingolipid lactoneotetraglycosylceramide . Mass spectrometric and composition analysis of the lipid A moiety shows that it is similar to the lipid A of Haemophilus influenzae strain I-69 Rd-/b+ proposed by Helander et al . (Helander, I . M., Lindner, B., Brade, H., Altmann, K., Lindberg, A . A., Rietschel, E . T., and Zahringer, U . (1988) Eur . J . Biochem . 177, 483-492) . Electrospray mass spectrometric analysis of the intact O-deacylated lipooligosaccharides gave an average Mr of 2710, and supported an overall structure consisting of the above nonasaccharide linked directly to a diphosphorylated lipid A moiety through the single KDO which is phosphorylated . This structure should provide a framework to investigate the roles of lipooligosaccharides in the host immunochemical response and pathology of H . ducreyi infection, a leading cause of genital ulcer disease. Presse Med, 1992 Jul 4-11, 21(25), 1160 - 4 {Value of corticosteroids in bacterial meningitis}; Merle M et al.; Bacterial meningitis mortality largely results from the intense host inflammation response to infection . Lysis of bacteria releases bacterial components that stimulate production of cytokines . Cerebrospinal fluid concentrations of these cytokines have been shown to correlate with the severity of the meningitis in both experimental and clinical situations . Dexamethasone has an antiinflammatory effect superior to methylprednisolone . It is the only agent with which significant clinical studies have yet been performed . A recent study recommends the routine use of dexamethasone with Haemophilus influenzae meningitis . The immediate and long-term clinical profiles indicate significantly better outcomes for the dexamethasone group . It is prudent to administer dexamethasone before the first parenteral dose of antibiotic to prevent the release of bacterial components induced by bacterial lysis . The search for agents that down modulate inflammation more strongly continues . Some monoclonal antibodies are superior to dexamethasone in experimental meningitis without modification of antibiotic pharmacokinetics. Pediatr Res, 1992 Jul, 32(1), 132 - 5 Vaccine-induced human antibody responses to the Haemophilus influenzae b polysaccharide in severe combined immunodeficient mice engrafted with human leukocytes; Lucas AH et al.; We examined the ability of severe combined immunodeficient (SCID) mice-human peripheral blood leukocyte (PBL) chimeras to respond to immunization with Haemophilus influenzae b polysaccharide (Hib PS) vaccines . Two to 3 wk after PBL engraftment, human-PBL-SCID mice, prepared with PBL from one of five adult donors, were immunized with free or protein-conjugated Hib PS . Antibody to Hib PS was quantitated in preimmunization and postimmunization sera . Before immunization, anti-Hib PS antibody was detectable (greater than 10 ng/mL) in three of 40 mice . Of the 37 human-PBL-SCID mice not having detectable serum antibody before immunization, 31 produced greater than or equal to 20 ng/mL (greater than or equal to 2-fold increase) anti-Hib PS antibody 2 to 3 wk after immunization . Both free and protein-conjugated forms of Hib PS were immunogenic . Geometric mean anti-Hib PS antibody levels ranged from 50 to 139 ng/mL . Vaccine-induced anti-Hib PS antibodies frequently expressed HibId-1, a cross-reactive idiotype that predominates the in vivo human antibody response to Hib PS . However, among mice engrafted with PBL from a single donor, the HibId-1 distribution was highly skewed, suggesting that clonally distinct B cells were being stimulated in individual mice . These findings indicate that human PBL transplanted into SCID mice are functionally responsive to Hib PS antigenic challenge . This system may serve as a useful model for studying the regulation and cellular requirements for human polysaccharide immunity. J Clin Microbiol, 1992 Jul, 30(7), 1879 - 81 Outer membrane protein subtypes of Haemophilus influenzae type b isolates causing invasive disease in Victoria, Australia, from 1988 to 1990; Clements DA et al.; Outer membrane protein subtyping of 187 isolates of Haemophilus influenzae type b (Hib), isolated from children with invasive Hib disease in Victoria, Australia, showed that a single outer membrane protein subtype (1VA) was responsible for 83% of the infections . It was identical to that responsible for the majority of cases of invasive Hib disease in Europe. J Clin Microbiol, 1992 Jul, 30(7), 1674 - 7 Investigation of ampicillin-intermediate strains of Haemophilus influenzae by using the disk diffusion procedure and current National Committee for Clinical Laboratory Standards guidelines; Heelan JS et al.; It was noted in our laboratory that certain strains of Haemophilus influenzae yielded zone sizes interpreted as resistant to the ampicillin (AMP) disk on chocolate-Mueller-Hinton agar (CMH) but showed no evidence of beta-lactamase (beta-Lac) activity . Although it is known that a second mechanism of AMP resistance exists, strains with this mechanism are uncommon . To investigate this apparent discrepancy, a study of 100 consecutive clinical isolates of H . influenzae collected over a 6-month period was performed . Isolates were simultaneously tested against five antibiotics (AMP, chloramphenicol, cefotaxime, ciprofloxacin, and AMP-sulbactam) on CMH and on two brands of Haemophilus test medium (HTM) by using the disk diffusion procedure and National Committee for Clinical Laboratory Standards (NCCLS) standards . By using CMH and NCCLS standard M2-A3-S2, strains of H . influenzae showing zone sizes of greater than or equal to 20 mm with AMP were considered sensitive . By using HTM and NCCLS standard M2-A4, strains showing zone sizes of greater than or equal to 25 mm to AMP on HTM were considered sensitive . Intermediate strains had zone sizes of 22 to 24 mm . The majority of isolates (68%) were sensitive to all antibiotics . Two percent of the isolates were resistant to chloramphenicol . Seventeen percent of the isolates were AMP-resistant, beta-Lac-producing strains of H . influenzae . Thirteen percent of the isolates gave at least one intermediate or resistant zone for AMP but were beta-Lac negative . MIC determinations with NCCLS standard M7-A2 were performed with resistant and intermediate strains . MICs for beta-Lac-producing strains of H . influenzae were >/= 8.0 microgram/ml . MICs for beta-Lac-negative strains were </= 1.0 microgram/ml and were highly reproducible . If one uses the current NCCLS zone diameter interpretive criteria, results should be viewed with caution . Further investigation of zone size interpretive criteria is warranted . It is suggested that in the case of serious infections with H . influenzae, beta-Lac-negative, AMP-resistant or -intermediate strains be confirmed by the MIC procedure. Arch Otolaryngol Head Neck Surg, 1992 Jul, 118(7), 749 - 52 Inhibition of lymphoproliferation by middle ear effusion in experimental otitis media; Diven WF et al.; In this study, experimental otitis media was created in the chinchilla by direct middle ear challenge with Escherichia coli endotoxin, Streptococcus pneumoniae, Haemophilus influenzae, or Pseudomonas aeruginosa . The effusions recovered from the chinchillas in all four challenge groups were shown to inhibit the lymphoproliferative response of chinchilla peripheral blood lymphocytes to stimulation with phytohemagglutinin . The effect was dose dependent, and for effusions of infectious origin, the degree of inhibition was directly related to the duration of infection . Presence of the inhibitor in plasma was undocumented, suggesting a local production within the middle ear . Lymphocytes from middle ears infected with bacteria but not middle ears challenged with endotoxin were hyporesponsive or nonresponsive to stimulation with phytohemagglutinin . These results confirm the presence of an inhibitor of the lymphoproliferative response in experimental otitis media of different etiologies. J Med Microbiol, 1992 Jul, 37(1), 43 - 50 Cytopathic effect of Haemophilus ducreyi for human foreskin cell culture; Alfa MJ; An explant adult foreskin cell culture (FS2-3) was compared with human lung carcinoma cell culture (A549) with regard to the ability of Haemophilus ducreyi to produce a cytopathic effect . The survival of H . ducreyi for up to 26 days in FS2-3 cells was far greater than in any previously described in-vitro culture system . H . ducreyi survived for up to 7 days in A549 cells . The H . ducreyi cells grew and formed "fungal-like" microcolonies on the eukaryotic monolayer . Portions of the microcolonies remained attached despite extensive washing . Transmission electronmicroscopy indicated that, at 48 h after infection, the H . ducreyi cells did not penetrate the FS2-3 cells but they were closely associated with them; there was only a 2-5 nm gap between the H . ducreyi cell wall and the FS2-3 membrane . The virulent H . ducreyi strains RO18 and 35,000 produced a cytopathic effect on FS2-3 cells that did not appear to be due to a soluble toxin . These strains did not produce any CPE on A549 cells . H . influenzae and the avirulent H . ducreyi strain CIP542, inoculated in the same concentration and incubated for the same length of time, did not produce CPE on FS2-3 cells . This study demonstrated that the use of FS2-3 foreskin cell culture provided an in-vitro approach for evaluating the cytopathic effect of virulent H . ducreyi whereby, unlike in other in-vitro systems, viability of the micro-organism could be readily maintained. Infect Immun, 1992 Jul, 60(7), 2992 - 4 Interaction of ruminant transferrins with transferrin receptors in bovine isolates of Pasteurella haemolytica and Haemophilus somnus; Yu RH et al.; The interactions of ruminant transferrins with receptors on bovine isolates of Pasteurella haemolytica and Haemophilus somnus were compared by growth studies and direct and competitive binding assays . Isolates of P . haemolytica were capable of utilizing and binding transferrin from sheep, goat, or cattle, whereas isolates of H . somnus were capable of utilizing and binding only bovine transferrin. Infect Immun, 1992 Jul, 60(7), 2986 - 91 Evidence for in vivo expression of transferrin-binding proteins in Haemophilus influenzae type b; Holland J et al.; Haemophilus influenzae type b acquires transferrin-bound iron via a siderophore-independent mechanism involving direct contact between the human iron-binding glycoprotein and the bacterial cell surface . Evidence has accumulated to show that the transferrin receptor consists of at least two iron-regulated outer membrane transferrin-binding proteins (TBPs), of which one has a molecular mass of around 100 kDa (TBP1) and the other has a molecular mass of 60 to 90 kDa (TBP2) . In H . influenzae type b strain Eagan, proteins of 76, 90, and 107 kDa appear to be involved in transferrin binding . To determine whether these TBPs are expressed during growth in vivo, strain Eagan was recovered without subculture from the intraperitoneal cavities of infected infant rats . By using a dot blot assay, outer membranes prepared from these in vivo-grown bacteria, unlike those grown in iron-sufficient broth, bound human transferrin and produced the 76-, 90-, and 107-kDa TBPs . Immunoblotting experiments using convalescent sera from infected rats also revealed the presence of antibodies to the 76- and 90-kDa strain Eagan TBPs . In addition, convalescent sera from three of four patients recovering from H . influenzae type b meningitis contained antibodies to the 90- and 105-kDa TBPs of the corresponding infecting strain . Furthermore, fresh clinical isolates of H . influenzae type b recovered from blood and cerebrospinal fluid showed constitutive expression of the TBPs, which became iron regulated only after prolonged in vitro subculture on iron-sufficient medium . This contrasted with the laboratory-adapted Eagan strain, in which the TBPs remained iron regulated even after animal passage . These findings indicate that the H . influenzae type b transferrin receptor is expressed during experimental animal and human infections. Infect Immun, 1992 Jul, 60(7), 2943 - 51 Phenotypic phase variation in Haemophilus somnus lipooligosaccharide during bovine pneumonia and after in vitro passage; Inzana TJ et al.; A high rate of phenotypic variation in the lipooligosaccharide (LOS) electrophoretic profile of Haemophilus somnus occurred in most isolates obtained at approximately weekly intervals from three calves intrabronchially challenged with a cloned isolate of H . somnus 2336 . Daily subculturing for 2 weeks resulted in at least one major alteration in the LOS electrophoretic profiles for strain 2336 and both additional disease isolates examined, but no change occurred in the LOS electrophoretic profiles for any of three commensal isolates examined . None of the LOSs from any of the postchallenge intrabronchial isolates reacted with rabbit antiserum to the challenge strain LOS in immunoblotting, but LOSs from two nasopharyngeal isolates did . Antigenic variation in the extracted LOSs of most of the isolates was supported by the results of an enzyme-linked immunosorbent assay . Preimmune serum from each of the calves did not react with any of the isolates or the challenge strain, whereas sera obtained 35 days after challenge reacted with the challenge strain and zero to five additional isolates and sera obtained 74 days after challenge reacted with two to six additional isolates . Recognition of LOSs from isolates obtained near the end of the 70-day experiment by day-74 sera was related to clearance of the bacteria from the lungs . Isolates demonstrating major electrophoretic changes showed variations in the composition of the oligosaccharide, but not lipid A, moiety of their LOSs . The oligosaccharide of the LOS of each isolate was composed predominantly of glucose but varied substantially in the contents of galactose, arabinose, xylose, mannose, and 3-deoxy-D-manno-octulosonic acid . Therefore, the LOS of H . somnus is capable of undergoing compositional and antigenic variations, which may act as an important virulence mechanism for evading host immune defense mechanisms. J Infect Dis, 1992 Jul, 166(1), 43 - 52 Growth of Haemophilus influenzae in human milk: synthesis, distribution, and activity of IgA protease as determined by study of iga+ and mutant iga- cells; Plaut AG et al.; The nonencapsulated, IgA protease-positive Haemophilus influenzae strain Rd and serogroup b clinical isolates were found to proliferate in human milk . Growth did not require supplemental X and V factors . In milk, strain Rd synthesized IgA protease, but it was completely inhibited by antibody, so secretory IgA in milk cultures remained intact . Inhibition was largely attributable to IgA1 antibodies . Rd cells also aggregated during growth in milk and showed colony size variation, whereas a protease-negative mutant of Rd (Rd225DK) aggregated less and had uniform colony size . Like differences in protease inhibition, these differences in growth pattern were mediated by secretory IgA1 . Thus, milk antibody not only inhibited the extracellular protease but also interacted directly with the enzyme precursor or related antigens on growing bacterial cells . This self-protective property of milk secretory IgA may be an important immunologic attribute for the upper respiratory mucosa of the infant. J Infect Dis, 1992 Jul, 166(1), 178 - 82 Type b capsule inhibits ingestion of Haemophilus influenzae by murine macrophages: studies with isogenic encapsulated and unencapsulated strains; Noel GJ et al.; Phagocytosis may be important in clearing Haemophilus influenzae from the bloodstream . To define the effect of type b capsule on phagocytosis, binding and ingestion by macrophages was measured for 5 isogenic sets of capsule-sufficient strains (clinical isolates and type b transformants of capsule-deficient mutants) and capsule-deficient mutants (strains lacking a 9-kb EcoRI fragment of chromosomal DNA associated with type b capsule expression) . Capsule-sufficient strains were not bound in the absence of serum, whereas capsule-deficient strains were bound and ingested (1.8-5.1 organisms/macrophage; 59%-97% ingested) . In the presence of nonimmune serum, capsule-sufficient strains were largely bound but not ingested (4.7-7.2 organisms/macrophage; 7%-21% ingested), whereas capsule-deficient strains were nearly all ingested (6.2-10.5 organisms/macrophage; 93%-97% ingested) . Strains resisting ingestion caused persistent bacteremia 24 h after intravenous challenge in mice and were more likely than readily ingested strains to cause persistent bacteremia or death in infant rats . Thus, type b capsule inhibits ingestion by macrophages; resistance to ingestion may be an important virulence determinant of type b organisms. Pediatr Infect Dis J, 1992 Jul, 11(7), 521 - 5 Children with Haemophilus influenzae bacteremia initially treated as outpatients: outcome in 85 American Indian children; Cortese MM et al.; Eighty-five American Indian children less than 16 years of age with Haemophilus influenzae bacteremia were retrospectively determined to have been treated as outpatients after their initial evaluation . We hoped to determine the proportion that developed new foci, the time interval to this development and whether age or temperature at presentation predicted outcome . Fifty-one (60%) presented with nonfocal findings . Seventy-two (85%) were treated with antibiotics at the initial visit . Although 49 (58%) of the patients were never hospitalized, a new focus was identified in 25 (29%), including 13 (15%) with a final diagnosis of meningitis . The new foci were identified within 6 days of presentation (median, 2 days) . An additional 15 (18%) patients had no new focus but were febrile and/or ill at follow-up . All patients with meningitis or a second positive culture were hospitalized at the first follow-up visit . Age and temperature at presentation did not help predict outcome . All patients with H . influenzae bacteremia require prompt reevaluation and close follow-up by an experienced physician. Pediatr Infect Dis J, 1992 Jul, 11(7), 516 - 20 Outcome of children with occult bacteremia caused by Haemophilus influenzae type b; Korones DN et al.; For better definition of the clinical course and outcome of children with occult bacteremia caused by Haemophilus influenzae type b (Hib), we reviewed the medical records of children who were initially managed as outpatients and subsequently found to be bacteremic . At Yale-New Haven Hospital (1971 to 1987) and the Children's Hospital of Philadelphia (1982 to 1987), 69 previously healthy children were identified with occult Hib bacteremia . Their median age was 14 months (range, 4 to 89 months) . Thirty-six (52%) of the 69 were either febrile and/or had a focus of serious infection at follow-up (meningitis (17), pneumonia (5), epiglottitis (3), cellulitis (5), and septic arthritis (3)) . Although the remaining 33 children (48%) were afebrile and appeared well on reevaluation, 3 of these 33 were still bacteremic and another 5 subsequently developed focal Hib infections . These 8 children were significantly younger (median age, 8.5 months) than the 25 children who remained well (median age, 16 months; P = 0.03) . Of the 28 children who had initially been treated with antimicrobials to which their organism was known to be susceptible, 12 (43%) were improved at reevaluation and remained well; 7 (23%) of the 31 patients who had not received such antimicrobials improved and remained well (P = 0.17) . Children initially managed as outpatients and later found to have had Hib bacteremia are at risk of subsequently developing a serious focal infection. Clin Ther, 1992 Jul-Aug, 14(4), 570 - 7 Cefaclor advanced formulation versus cefaclor in the treatment of pneumonia; Casali L et al.; The use of cefaclor advanced formulation (cefaclor AF) in the treatment of pneumonia caused by susceptible organisms was investigated in a multi-center trial conducted in the United Kingdom and the United States . A total of 266 patients were enrolled in this double-blind, double-dummy, randomized, parallel study; 132 patients were treated with cefaclor AF and 134 patients received the reference drug cefaclor . Inclusion criteria were a diagnosis of lobar pneumonia or bronchopneumonia, with a positive sputum culture and an infiltrate on chest roentgenogram . Patients received either cefaclor AF (750 mg twice daily) or cefaclor (500 mg three times daily) for 10 to 14 days . Forty patients in the cefaclor AF group and 45 in the cefaclor group were evaluable for efficacy, with 37 (92.5%) and 43 (95.6%), respectively, showing a favorable posttherapy clinical response . Proven or presumed pathogen elimination was achieved in 87.5% and 86.7% of cases, respectively . Both study drugs demonstrated high levels of activity against Streptococcus pneumoniae, Haemophilus influenzae (including beta-lactamase-producing strains), and Moraxella catarrhalis (including beta-lactamase-producing strains) . There were no statistically significant differences between drugs in efficacy results . One or more side effects were reported by 42.4% of the patients treated with cefaclor AF and by 44.0% of those treated with cefaclor; diarrhea, nausea, headache, and respiratory disorders were the most common adverse events . No drug-related side effects were seen with a frequency or severity that would be unexpected with the use of oral cephalosporins . Cefaclor AF and cefaclor performed equally well with respect to clinical and bacteriologic response rates in the treatment of pneumonia. Jpn J Antibiot, 1992 Jul, 45(7), 897 - 904 {Studies on meropenem in the field of pediatrics}; Haruta T et al.; The pharmacokinetics and the clinical effectiveness of meropenem (MEPM) were examined in the field of pediatrics . The results are summarized as follows . 1 . A 4-year-6-month-old girl with suppurative meningitis (Haemophilus influenzae) was treated by intravenous drip infusion of MEPM in a daily dose of 29 mg/kg which was divided into 4 dosages, each dosage being infused over 30 minutes, and the drug concentration in cerebrospinal fluid was determined . Upon completion of infusion on the 2nd day of treatment, the drug concentration was 2.52 micrograms/ml, which corresponded to 3.6% of the drug concentration in the blood . 2 . MEPM was used in 10 patients, including 3 with suppurative lymphnoditis, 2 with staphylococcal scalded skin syndrome (SSSS) and 1 each with pneumonia, suppurative meningitis, suppurative knee arthritis, facial phlegmon and pyelonephritis . The daily doses ranged from 30 to 117.6 mg/kg, divided into 3 to 4 dosages and administered via intravenous drip infusion over 30 minutes . Clinical responses were evaluated as very good in 7 patients, good in 2 patients and fair in 1 patient, with an efficacy rate of 90% . 3 . Isolated pathogens were 2 strains of Staphylococcus aureus, 1 strain of Klebsiella pneumoniae and 3 strains of Haemopilus influenzae . All of the 6 strains were eradicated, with an eradication rate of 100% . 4 . In the safety evaluation, none of the patients was observed to have any side effects . Furthermore, no abnormal variations were found in laboratory test data possibly attributable to administration of MEPM. N Y State J Med, 1992 Jul, 92(7), 297 - 300 Bronchitis mimicking opportunistic lung infection in patients with human immunodeficiency virus infection/AIDS; Chechani V et al.; Purulent bronchitis was identified in 19 of 422 patients undergoing fiberoptic bronchoscopy during a 32-month period because of suspicion of an opportunistic lung infection complicating acquired immunodeficiency syndrome or human immunodeficiency virus infection . Five patients had Pneumocystis carinii pneumonia, but other opportunistic lung infections were excluded in the remaining 14 patients . Characteristics of these 14 patients included fever (greater than 38.3 degrees C), cough, and dyspnea in 14 of 14 patients; purulence of expectorated sputum (11/14); and widened alveolar-arterial oxygen gradient (13/14) . Rapid (2 +/- 1.4 days) clinical response (defervescence and resolution of pulmonary symptoms) occurred with antibiotic therapy in 10 of 14 patients . In three patients, there was no improvement, and adult respiratory distress syndrome developed . Bacterial isolates from bronchoalveolar lavage included Streptococcus viridans (n = 12), Haemophilus influenzae (n = 7), Staphylococcus aureus (n = 3) . Roentgenographic features of bronchiectasis were present in seven patients . Differential cell counts revealed greater than 50% neutrophils in the bronchial washings of all patients with purulent bronchitis . Neutrophil percentages in bronchoalveolar lavage were as follows: patient with purulent bronchitis without P carinii pneumonia (n = 14), 54.53% +/- 29.18%; patients with purulent bronchitis and concomitant P carinii pneumonia (n = 5), 62% +/- 31.9% . In a control group of 17 patients with P carinii pneumonia who did not have purulent bronchitis, the neutrophil percentage was 6.8% +/- 6.17% (p = less than 0.00001, t-test) . Purulent bronchitis appears to be a distinct, treatable entity in patients with HIV infection and may accompany bacterial pneumonia, bronchiectasis, and P carinii pneumonia. Vet Microbiol, 1992 Jul, 32(1), 43 - 9 Efficacy of a trivalent Haemophilus paragallinarum vaccine compared to bivalent vaccines; Jacobs AA et al.; The efficacy of a trivalent oil-adjuvant Coryza vaccine containing serotypes A, B and C of Haemophilus paragallinarum has been compared with that of a bivalent oil-adjuvant Coryza vaccine containing serotypes A and C and that of a commercially available, bivalent A1(OH)3-potentiated vaccine, containing types A and C . The trivalent vaccine, given at 10 and 17 weeks of age, provided the best protection . Even at 55 weeks after booster vaccination, chickens were still significantly protected, following severe challenge with either of the three serotypes of Haemophilus paragallinarum . Both bivalent vaccines did not protect against type B challenge . Furthermore the oil-adjuvant vaccines induced higher HI-A titers, which correlate with protection, compared to the A1(OH)3-potentiated vaccine . The results show that type B strains are pathogenic and constitute a distinct immunotype and thus a Coryza vaccine should contain three serotypes to obtain a broader protection against all serotypes. Mol Microbiol, 1992 Jul, 6(14), 1895 - 902 Two linked genes for outer membrane proteins are absent in four non-disease strains of Haemophilus somnus; Cole SP et al.; Linked genes encoding two outer membrane proteins (p76 and a family of proteins, p120) of the bovine pathogen, Haemophilus somnus, were investigated . The p120 group was previously shown to have immunoglobulin-binding activity and to react with polyclonal antiserum specific for a 270 kDa antigen (p270) which also had immunoglobulin Fc-binding activity . By Western blotting we showed that the p76 antigen also reacted with this antiserum . The p270, p120, and p76 antigens were undetectable in four serum-sensitive isolates from asymptomatic carriers but were present in the two serum-resistant virulent strains tested . Genes for p120 and p76 were subcloned on non-overlapping pUC plasmids from a cosmid (pHS1) originally cloned from a serum-resistant strain . In Escherichia coli, plasmid pHS138 expressed p76, while the p120 antigens were produced by pHS140 . Southern blots of DNA from the above six strains of H . somnus using probes derived from pHS1 subclones showed that a 13.4 kb sequence was missing from the four serum-sensitive strains, but not the two serum-resistant strains . This segment included most of the insert in pHS138 and all of the pHS140 insert . The data indicate that p76 and the p120 proteins are absent from serum-sensitive strains because the coding sequences are missing, raising the possibility of insertion of these genes into the chromosome of both serum-resistant strains, or deletion from the four serum-sensitive strains. Am J Vet Res, 1992 Jul, 53(7), 1113 - 8 Stimulation and suppression of the oxygenation activity of porcine pulmonary alveolar macrophages by Actinobacillus pleuropneumoniae and its metabolites; Dom P et al.; The effects of Actinobacillus (Haemophilus) pleuropneumoniae and its metabolites on the oxygenation activity of porcine pulmonary alveolar macrophages (PAM) were studied, using a chemiluminescence technique . Actinobacillus pleuropneumoniae strains of serotypes 2, 3, and 9 in a dose of 1, 10, and 100 colony-forming units/macrophage first stimulated the oxygen radical production of PAM . After having reached a peak value, oxygenation activity decreased, finally resulting in total suppression of PAM . All these effects were neutralized by homologous convalescent pig sera that had been adsorbed onto inactivated A pleuropneumoniae strains . Moreover, cross-neutralization was shown between serotypes 2 and 3 . Inactivated A pleuropneumoniae strains did not influence the oxidative activity of PAM . Undiluted and lower dilutions of sterile A pleuropneumoniae culture supernatants were toxic for PAM, whereas higher dilutions of the supernatants stimulated oxygen radical production of the macrophages . These effects were heat-sensitive and were neutralized by homologous convalescent pig sera . Cross-neutralization was shown between serotypes 2 and 3 . These findings indicated that stimulation and inhibition of the oxygenation activity of PAM are attributable to heat-sensitive metabolites produced by A pleuropneumoniae. Kansenshogaku Zasshi, 1992 Jul, 66(7), 956 - 63 {Dynamic process of colonization by Haemophilus influenzae in children--is H . influenzae normal flora in the throat?}; Takahashi A et al.; Eighty-seven oropharyngeal isolates of Haemophilus influenzae were obtained by two time cultures six months apart from a total of 288 children who attend a kindergarten . We analyzed the strains by comparing their serotypes, biotypes, beta-lactamase activity and by performing electrophoresis of outer membrane proteins on polyacrylamide gels . Only nineteen strains were not identical, the rest of the 68 strains were classified into 23 types . During 6 months at least 15 types of strains lost from this group and 21 types of new strains were obtained . There were no children who had identical pairs of H . influenzae in their oropharynx during the 6 months . The classification of strains in oropharynx suggested that person-to-person transmission of nontypable H . influenzae can occur . We concluded that oropharyngeal colonization by nontypable H . influenzae is not a normal flora in children. J Antimicrob Chemother, 1992 Jul, 30(1), 67 - 71 Concentrations of cefpodoxime in serum and bronchial mucosal biopsies; Baldwin DR et al.; Cefpodoxime proxetil is a new orally administered cephalosporin which has a favorable spectrum of activity against respiratory pathogens . Concentrations of cefpodoxime in serum and bronchial mucosal biopsy were measured in 13 patients without active respiratory tract infection undergoing fibreoptic bronchoscopy . Samples were taken between 1 and 6 h after a single oral dose of cefpodoxime proxetil equivalent to 200 mg of cefpodoxime base . In twelve patients who completed the study, mean serum concentrations were 1.7 mg/L (S.E.M . 0.4) and in ten patients mean bronchial biopsy concentrations were 0.9 mg/L (S.E.M . 0.2) . The mean penetration was 54% (S.E.M . 6.1) . Cefpodoxime was undetectable in biopsies from two patients . The majority of serum and biopsy concentrations were in excess of the MIC90S for Haemophilus influenzae and Streptococcus pneumoniae . Cefpodoxime proxetil may be worthy of further study in clinical trials in patients with respiratory infections. Can J Vet Res, 1992 Jul, 56(3), 177 - 83 Changes in the bacterial flora of the upper and lower respiratory tracts and bronchoalveolar lavage differential cell counts in feedlot calves treated for respiratory diseases; Allen JW et al.; Serial nasopharyngeal swab and bronchoalveolar lavage cultures were used to estimate changes in the bacterial flora of the respiratory tracts of calves during the first month after arrival in the feedlot . Bronchoalveolar lavage (BAL) differential cell counts served to evaluate pulmonary inflammatory changes during this period . Two groups of calves were studied, one consisting of clinically normal controls (n = 60), the other, of cases (n = 59) which received treatment for respiratory disease (penicillin +/- trimethoprimsulfadoxine) . A variety of organisms, including Pasteurella multocida, Pasteurella haemolytica, Haemophilus somnus, Mycoplasma bovis and Mycoplasma bovirhinis, were present in the upper and lower airways of both groups during the postarrival period . With the exception of M . bovis, an overall decline in the prevalence of these organisms was observed during the course of the study . In cases, there was a marked decrease in the number of Pasteurella spp . and H . somnus isolates immediately following treatment . For the Pasteurella spp., however, this effect was shortlived as they often appeared to recolonize the respiratory tract within eight days of terminating antimicrobial therapy . Treatment did not appear to affect the frequency of isolating M . bovis . Its prevalence, in both groups of calves, increased to levels approaching 100% during the course of the study . All Pasteurella spp . isolates were tested for susceptibility to several commonly used antimicrobials . Resistance was only evident among P . haemolytica isolated from cases and in every instance this was to a combination of penicillin, ampicillin and tetracycline . Significantly more isolates were resistant after treatment than before . There were BAL differential cell count abnormalities indicative of inflammation in both cases and controls.(ABSTRACT TRUNCATED AT 250 WORDS) Avian Dis, 1992 Jul-Sep, 36(3), 655 - 63 Correlation between the ability of Haemophilus paragallinarum to acquire ovotransferrin-bound iron and the expression of ovotransferrin-specific receptors; Ogunnariwo JA et al.; To investigate the mechanisms of iron acquisition in avian haemophili, strains of Haemophilus paragallinarum and H . avium were tested for siderophore production and utilization of transferrin iron for growth . No evidence of siderophore production was detected in either of these species using a functional screening assay . H . paragallinarum, but not strains of H . avium, was able to acquire iron from 30% saturated chicken and turkey transferrins but not from human, porcine, or bovine transferrins . In response to iron limitation, H . paragallinarum expressed four iron-regulated outer-membrane proteins of 53, 62, 66, and 94 kilodaltons (kDa) . Only the 53- and 94-kDa proteins were detected in the H . avium strains . Using affinity methods, the 94- and 53-kDa proteins were isolated specifically by chicken or turkey transferrin, indicating that they may be equivalent to transferrin binding proteins (TBP1 and TBP2, respectively) isolated from other bacterial species . The isolation of the 62- and 66-kDa proteins in association with TBP1 and TBP2 under less stringent washing conditions only in H . paragallinarum implicates these proteins in the iron acquisition process. Avian Dis, 1992 Jul-Sep, 36(3), 632 - 6 An evaluation of inactivated infectious coryza vaccines containing a double-emulsion adjuvant system; Blackall PJ et al.; The efficacy of experimental inactivated infectious coryza vaccines produced by a commercial vaccine manufacturer was evaluated . The vaccines, containing as the adjuvant phase either a double-emulsion mineral oil system or aluminum-hydroxide gel, were administered to 6-week-old chickens as a single dose . Some vaccines were a monovalent product containing a Page serovar C Haemophilus paragallinarum strain, and others were a bivalent product containing both Page serovar A and serovar C strains . After 3 weeks, all chickens were challenged by infraorbital sinus inoculation of virulent H . paragallinarum, either Page serovar C (strain HP31) or Page serovar A (strain HP14) . The monovalent serovar C double-emulsion-based vaccines gave significant protection against a serovar C challenge, with the level of protection varying from 60% to 100% . The monovalent serovar C aluminum-hydroxide-gel vaccine also gave significant protection (94%) against a serovar C challenge . The bivalent double-emulsion vaccine gave significant protection against challenge from both serovars (100% for serovar C and 83% for serovar A) . Although no major adverse reactions were detected, some chickens receiving both the double-emulsion vaccines and the aluminum-hydroxide vaccine developed relatively minor granulomatous reactions at the site of injection. Nihon Kyobu Shikkan Gakkai Zasshi, 1992 Jul, 30(7), 1250 - 6 {Clinical significance of respiratory infections associated with lung cancer patients}; Watanabe A et al.; An attempt was made to interpret the clinical significance of secondary infections associated with lung cancer . The incidence of secondary infections was 51.4% in 214 in-patients with lung cancer in our institution in 1988 and 1989, and almost all of them had respiratory infections caused by commonly encountered bacteria . The incidence of infection was high in lung cancer of cell types other than adenocarcinoma, and in those with hypoalbuminemia, impaired cellular immunity and obstruction of the airway . The prognosis in patients with infection was much poorer than that in patients without infection . Major pathogens responsible for infection were Staphylococcus aureus including methicillin-resistant S . aureus (MRSA), Haemophilus influenzae, Klebsiella spp . and Pseudomonas aeruginosa . These pathogens, except for H . influenzae, were isolated in the terminal stage in cases with airway obstruction and post cancer chemotherapy . The efficacy rate of 194 therapeutic regimens against infection was 57.7% . It was thus found that the efficacy rate in 1988 and 1989 exceeded that in the 1970s . The effectiveness was very poor for infections caused by S . aureus and P . aeruginosa, and for cases with airway obstruction and marked impairment of pulmonary blood flow . The efficacy rate of single-drug regimens was 57.1% (80/140) and that of combined regimens was 59.3% (32/54) . The above results indicate that a new combined therapy which includes a beta-lactam antibiotic as well as measures to improve the general health of compromised hosts are required in the treatment of secondary infections in these patients. J Med Primatol, 1992 Jul, 21(5), 275 - 8 Identification of two subclasses of IgA in the chimpanzee (Pan troglodytes); Cole MF et al.; Chimpanzee secretory immunoglobulin A (SIgA) was separated into two fractions by chromatography using the terminal galactose-binding lectin Jacalin . The SIgA fraction bound by Jacalin was cleaved by Haemophilus influenzae IgA1 protease, whereas the SIgA nonbinding fraction was not cleaved . It is proposed that these fractions represent IgA1 and IgA2 subclasses because the presence or absence of galactose-terminal oligosaccharides (Jacalin binding) and susceptibility or resistance to IgA1 protease are properties that define human IgA1 and IgA2 subclasses. Indian J Med Res, 1992 Jul, 95, 187 - 9 Multiply resistant Haemophilus influenzae type b causing meningitis; Amarnath SK et al.; The isolation from patients of meningitis, of two multidrug resistant strains of H . influenzae is of relevance to the empirical treatment of meningitis patients . The isolates produced beta lactamase and had higher MICs as compared to the four H . influenzae strains sensitive to the drugs commonly used for the treatment of meningitis . The cephalosporins and gentamicin were found to be effective antibiotic agents . The occurrence of resistance to ampicillin, chloramphenicol, cloxacillin, cotrimoxazole, tetracycline, penicillin and erythromycin is of concern. Eur J Clin Microbiol Infect Dis, 1992 Jul, 11(7), 646 - 52 Comparative in vitro activity of cefdinir (CI-983; FK-482) against staphylococci, gram-negative bacilli and respiratory tract pathogens; Scriver SR et al.; The in vitro activity of cefdinir (CI-983; FK-482), a new oral cephalosporin, was compared with that of other antimicrobial agents against clinical isolates of staphylococci, gram-negative bacilli and common respiratory tract pathogens . Cefdinir (MIC90 less than or equal to 2.0 micrograms/ml) was more active than cefixime (MIC90 greater than 64 micrograms/ml) and equally as active as cefuroxime (MIC90 2.0 micrograms/ml) against oxacillin-susceptible staphylococci . Cefdinir was active against Haemophilus influenzae, including beta-lactamase producers (MIC90 0.5 microgram/ml), Moraxella catarrhalis (MIC90 less than or equal to 0.12 microgram/ml), Streptococcus pneumoniae (MIC90 less than or equal to 0.06 microgram/ml) and Streptococcus pyogenes (MIC90 less than or equal to 0.06 microgram/ml) . The activity of cefdinir against gram-negative bacilli was variable; organisms with chromosomal cephalosporinases were often resistant. Drugs, 1992 Jul, 44(1), 117 - 64 Clarithromycin . A review of its antimicrobial activity, pharmacokinetic properties and therapeutic potential; Peters DH et al.; Clarithromycin is an acid-stable orally administered macrolide antimicrobial drug, structurally related to erythromycin . It has a broad spectrum of antimicrobial activity, similar to that of erythromycin and inhibits a range of Gram-positive and Gram-negative organisms, atypical pathogens and some anaerobes . Significantly, clarithromycin demonstrates greater in vitro activity than erythromycin against certain pathogens including Bacteroides melaninogenicus, Chlamydia pneumoniae, Chlamydia trachomatis, Mycobacterium chelonae subspecies--chelonae and--abscessus, Mycobacterium leprae, Mycobacterium marinum, Mycobacterium avium complex, Legionella spp . and, when combined with its 14-hydroxy metabolite, against Haemophilus influenzae . However, bacterial strains resistant to erythromycin are also generally resistant to clarithromycin . The antimicrobial activity of clarithromycin appears to be enhanced by the formation in vivo of the microbiologically active 14-hydroxy metabolite . In combination, additive or synergistic activity against a variety of pathogens including Haemophilus influenzae, Moraxella catarrhalis, Legionella species (principally Legionella pneumophila) and various staphylococci and streptococci has been demonstrated . Clarithromycin has a superior pharmacokinetic profile to that of erythromycin, allowing the benefits of twice daily administration with the potential for increased compliance among outpatients where a more frequent regimen for erythromycin might otherwise be indicated . The clinical efficacy of clarithromycin has been confirmed in the treatment of infections of the lower and upper respiratory tracts (including those associated with atypical pathogens), skin/soft tissues, and in paediatrics . Clarithromycin was as effective as erythromycin and other appropriate drugs including beta-lactams (penicillins and cephalosporins) in some of the above infections . A most promising indication for clarithromycin appears to be in the treatment of immunocompromised patients infected with M . avium complex, M . chelonae sp . and Toxoplasma sp . Small initial trials in this setting reveal clarithromycin alone or in combination with other antimicrobials to be effective in the eradication or amelioration of these infections . Noncomparative studies have provided preliminary evidence for the effectiveness of clarithromycin in the treatment of infections of the urogenital tract, oromaxillofacial and ophthalmic areas . However, the promising in vitro and preliminary in vivo activity of clarithromycin against Mycobacterium leprae and Helicobacter pylori warrant further clinical trials to assess its efficacy in patients with these infections . Despite the improved pharmacokinetic profile and in vitro antimicrobial activity of clarithromycin over erythromycin, comparative studies of patients with community-acquired infections reveal the 2 drugs to be of equivalent efficacy . However, clarithromycin demonstrates greater tolerability, principally by inducing fewer gastrointestinal disturbances.(ABSTRACT TRUNCATED AT 400 WORDS) Microb Pathog, 1992 Jul, 13(1), 81 - 4 Binding of Haemophilus ducreyi to extracellular matrix proteins; Abeck D et al.; A collection of Haemophilus ducreyi isolates were screened for the ability to bind to fibrinogen, fibronectin, collagen, gelatin and laminin by a particle agglutination test using latex beads coated with the individual proteins . Thirteen of 21 isolates reacted with all five extracellular matrix proteins . Binding of organisms to protein-coated latex beads was inhibited by pretreatment of the bacteria with detergent, trypsin or boiling . Two isolates did not bind to collagen and gelatin with one of these not reacting with laminin either . Seven strains which failed to react with laminin did not express pili when examined by electron microscopy . This observation suggests a specific interaction with the pili of H . ducreyi. Med Trop (Mars), 1992 Jul-Sep, 52(3), 267 - 71 {Surveillance of the sensitivity of antibiotics to the principal germs responsible for purulent meningitis at the University Hospital Center in Treichville from 1986 to 1991}; Edoh V et al.; Between January 1986 and December 1991, the sensitivity of germs isolated from purulent meningitidis diagnosed at the Universitary and Hospital Center Treichville was tested with reference to the antibiotics utilized in the treatment of purulent meningitidis (Ampicillin, cefotaxime, amoxicillin+clavulinic acid, chloramphenicol, gentamicin and Trimethoprim-sulfamethoxazole)) . Cefotaxime, cephalosporin of the third generation, keeps its effectiveness on the main germs as a whole (Pneumococcus, Meningococcus, haemophilus influenzae) . On the contrary, the other antibiotics undergo some fluctuations, or their activities are declining year after year . As far as etiology is concerned, pneumococcus always takes the first place, then come Haemophilus influenzae and Meningococcus. Antimicrob Agents Chemother, 1992 Jul, 36(7), 1412 - 7 Activity and local delivery of azithromycin in a mouse model of Haemophilus influenzae lung infection; Vallee E et al.; We compared the activities of azithromycin and erythromycin against Haemophilus influenzae in a mouse model of nonparenchymatous lower respiratory tract infection . In vitro and in vivo efficacy data for both drugs were analyzed relative to their pharmacokinetics in lungs and in vivo uptake by phagocytes . Aged C57BL/6 mice (mean age, 15.1 +/- 1.9 months) were infected intratracheally with 10(8) CFU of H . influenzae serotype b . Oral drug administration was initiated 4 h after infection by various dosage regimens . In terms of bacterial killing in the lung, azithromycin was much more active than erythromycin (P less than 0.01) . Its in vivo activity was also more durable after a single administration relative to the durability of three doses of erythromycin given at 6-h intervals . The MIC of azithromycin was eightfold lower than that of erythromycin, and better penetration and a longer half-life in lung tissue were achieved after a single oral administration . Phagocytes delivered increased amounts of both drugs to the infected lungs, particularly at the site of infection (bronchoalveolar airspaces), and detectable levels of azithromycin were maintained locally for long periods . The fact that the efficacy of azithromycin coincided with the arrival of large numbers of polymorphonuclear leukocytes within the airspaces suggests that active extracellular concentrations were provided by the release of azithromycin from these cells . This further supports the potential value of once-daily azithromycin regimens for the treatment of lower respiratory tract infections in humans, provided that inhibitory concentrations against common pathogens such as H . influenzae are maintained for adequate periods of time. Ann Ital Med Int, 1992 Jul-Sep, 7(3 Suppl), 86S - 93S {Antibiotic therapy in bronchopulmonary infections}; Moroni M et al.; Because of difficulties in accurately determining an etiologic diagnosis, the ideal treatment for lower respiratory tract infections remains questionable . Suggested regimens are made on the basis of clinical and epidemiological data . However, the single most common pathogen responsible for pneumonia remains Streptococcus pneumoniae . Atypical pneumonia in younger patients is best treated with macrolides . Older patients without debility or immunodepression are best treated with amoxycillin-ampicillin, second generation cephalosporins or cotrimoxazole, on the basis of local susceptibility patterns of microorganisms . In the treatment of acute bacterial bronchitis in chronic bronchial disease, most antimicrobial agents with activity in vitro against Haemophilus influenzae and Streptococcus pneumoniae are clinically efficacious . Among new pathogens, the importance of Chlamydia pneumoniae is variable according to the studies, and Moraxella catarrhalis was considered almost exclusively responsible for purulent exacerbations of chronic bronchitis . Therapy for empiric treatment of nosocomial pneumonia must ensure coverage for aerobic Gram negative bacilli: the most frequently used includes a semisynthetic penicillin plus an aminoglycoside, but monotherapy with newer broad-spectrum antibiotics (imipenem, ceftazidime, ciprofloxacin, timentin, etc.) seems to be equivalent to combination regimens . The lung is the most common target organ for infectious complications in immunocompromised patients but the diagnostic methods employed in the traditional work-up of pneumonia are often of little or no use in this setting . By far the two most useful clues to management of pneumonia in the immunocompromised host are the underlying host defect and the radiographic pattern of the lung infiltrate.(ABSTRACT TRUNCATED AT 250 WORDS) Ann Ital Med Int, 1992 Jul-Sep, 7(3 Suppl), 74S - 77S {The etiology of bacterial respiratory infections in adulthood}; Nicoletti G; Upper and lower respiratory tract infections are the most frequently reported pathologies both in children and in adults . In particular, the most common clinical pictures are otitis media, principally chronic, and acute and chronic sinusitis . The microbiology of otitis media, which has been investigated thoroughly in the last year, confirmed a bacterial origin in 90% of the cases (while the incidence of the viral form is low) . The etiologic agents responsible for chronic infections are Gram-negative bacteria, staphylococci and anaerobic bacteria, while in the acute forms, which are rare in adults but frequent in children, the responsible pathogens are principally Haemophilus influenzae, Streptococcus pyogenes and Branhamella catarrhalis . Among the etiologic agents of chronic sinusitis, which, from a clinical point of view, is the most frequently observed, there are staphylococci, Streptococcus pyogenes and many anaerobic bacteria . As regards lower respiratory tract infections, chronic bronchitis is the most frequent pathology in adults . But, in this case, the etiologic agents are more difficult to identify . Analysing the above-mentioned clinical pictures and their relevant etiologic agents, among the different therapeutic proposals, one of the most innovative and recent is represented by azithromycin . Azithromycin is the first of a new class of macrolides termed "Azalides" which shows particular microbiological and pharmacokinetic characteristics . As compared to other macrolides, it has an higher distribution volume, a longer half-life, a deeper intracellular penetration and a wider spectrum of action . It is rapidly concentrated in leukocytes PMN, monocytes, macrophages and fibroblasts and slowly released by these cells to the infected tissues . Azithromycin concentrations in tissues and sites of infection can be increased by the phagocyte uptake.(ABSTRACT TRUNCATED AT 250 WORDS) Am J Med, 1992 Jun 22, 92(6A), 7S - 15S In vitro activity of loracarbef and effects of susceptibility test methods; Doern G; Loracarbef is a new oral antimicrobial of the carbacephem class with in vitro activity against the common pathogens associated with skin infections, otitis media, sinusitis, bronchopulmonary infections, and urinary tract infections . A review of the literature shows the following ranges for 90% minimum inhibitory concentration (MIC90) values (microgram/mL) against the organisms that commonly cause these illnesses: Streptococcus pneumoniae, 0.25-2.0; Moraxella (Branhamella) catarrhalis (beta-lactamase positive), 0.5-8.0; M . catarrhalis (beta-lactamase negative), 0.12-0.25; Haemophilus influenzae (beta-lactamase positive), 0.5-16.0; H . influenzae (beta-lactamase negative), 0.25-8.0; Escherichia coli, 2.0-25; Klebsiella pneumoniae, 0.25-8.0; Proteus mirabilis, 1.0-8.0; Streptococcus pyogenes, less than or equal to 0.06-1.0; Staphylococcus aureus (beta-lactamase positive), 8.0; S . aureus (beta-lactamase negative), 1.0-2.0 . The in vitro activity of loracarbef against these common outpatient pathogens is similar to that of other oral antimicrobials such as cefaclor, cefuroxime axetil, cefixime, amoxicillin/clavulanate, and trimethoprim/sulfamethoxazole . The results of in vitro susceptibility tests with any antimicrobial, including loracarbef, are somewhat dependent on the specific test method that is employed in the laboratory . This is particularly true with H . influenzae . Furthermore, the results of loracarbef susceptibility tests are of uncertain value in predicting therapeutic outcome. Am J Med, 1992 Jun 22, 92(6A), 53S - 57S Acute bronchitis: results of U.S . and European trials of antibiotic therapy; Dere WH; Acute bronchitis, an illness frequently encountered by primary-care physicians, is an inflammation of the tracheobronchial tree that results from a respiratory tract infection . It is characterized by persistent cough and sputum production and is occasionally accompanied by fever and/or chest pain . Acute bronchitis may have a viral or bacterial origin and is often treated with antibiotics . Four clinical trials were conducted to compare high and low doses of loracarbef, a new oral beta-lactam antibiotic, with three agents commonly used to treat acute bronchitis: amoxicillin/clavulanate, cefaclor, and amoxicillin . Results of these studies indicated that loracarbef, 400 and 200 mg twice daily, had clinical and bacteriologic efficacy against the common respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella (Branhamella) catarrhalis that was comparable with that of the comparative agents . Loracarbef was as well tolerated as cefaclor and amoxicillin; moreover, it produced a significantly lower incidence of diarrhea than did amoxicillin/clavulanate . Loracarbef may be considered a safe and effective alternative agent for the treatment of patients with acute bronchitis. Br J Hosp Med, 1992 Jun 17-30, 48(1), 44 - 6 Haemophilus influenzae type b vaccines; Howard AJ; Haemophilus influenzae type b (Hib) is a major cause of serious infections in childhood . New vaccines have been developed which are effective in invoking immunity against this organism when administered to children of all ages, including young infants . Their widespread introduction in the UK should lead to a dramatic decline in the incidence of Hib disease. Vet Microbiol, 1992 Jun 15, 31(4), 363 - 8 Occurrence of V-factor (NAD) independent strains of Haemophilus paragallinarum; Mouahid M et al.; Strains of Bisgaard taxon 31, isolated from chickens in South Africa suffering from a respiratory disease with clinical symptoms and gross lesions similar to infectious coryza, showed great phenotypical similarities with Haemophilus paragallinarum infection except for NAD requirement, beta-galactosidase activity and maltose fermentation . Deoxyribonucleic acid-deoxyribonucleic acid hybridization confirmed a high level of genetic relatedness (DNA binding value, 89%) with Haemophilus paragallinarum . Guanine + cytosine content and genome size data also support the classification of taxon 31 strains within the species Haemophilus paragallinarum. J Infect Dis, 1992 Jun, 165 Suppl 1, S86 - 9 Outer membrane proteins P1 and P2 of Haemophilus influenzae type b: structure and identification of surface-exposed epitopes; Munson R Jr et al.; The outer membrane proteins (OMPs) P1 and P2 of Haemophilus influenzae type b exhibit molecular size and antigenic variation . Their structural genes have been cloned from prototype isolates of the most common disease-producing clonal groups . The derived amino acid sequences of P1 from strains of OMP subtypes 1H, 3L, and 6U have three variable regions between highly conserved regions . An immunodominant surface-exposed epitope was identified near the carboxyl terminus of P1 proteins from subtype 1H and 3L strains . The P2 genes from subtype 1H, 1L, and 3L isolates were identical . The P2 gene sequence from a subtype 6U isolate differs from the subtype 1H P2 gene by 13 nucleotides, resulting in 10 amino acid changes . The P2 gene from a subtype 2L isolate differs by 1 nucleotide from the subtype 1H P2 gene, resulting in 1 amino acid change at position 166 . Two surface-exposed epitopes of OMP P2 were identified, one each between residues 158 and 174 and residues 319 and 341. N Z Med J, 1992 Jun 10, 105(935), 218 - 20 Haemophilus influenzae in New Zealand: subtyping of isolates from invasive disease using outer membrane protein profiling; Saravani GA et al.; Invasive Haemophilus influenzae type b disease affects one in every 350 New Zealand children by the age of five, leaving some with severe handicap . As part of a national surveillance programme aimed at determining the epidemiology of H influenzae b disease in this country, the diversity of local isolates causing invasive disease was examined using outer membrane protein (OMP) profiling . Of 81 H influenzae b isolates examined, 70 (86%) had identical OMP profiles . Among the other 11 H influenzae b isolates, eight different OMP profiles were observed . Nontype b Haemophilus influenzae isolates (n = 13) showed a greater diversity of OMP patterns. Monatsschr Kinderheilkd, 1992 Jun, 140(6), 363 - 5 {Environmental chemoprevention of Haemophilus influenzae type B meningitis . Consequences of 2 indirectly related case pairs}; Hoppe JE et al.; BACKGROUND: Within a few months we twice observed the following situation: In each of two different communities, a young child fell ill with meningitis caused by Haemophilus influenzae type B (HIB) . One week later, a second case occurred in the same community . Both patients had had no direct contact with each other . But each had an asymptomatic older sibling . These siblings attended the same kindergarten and had close contact with each other . The isolated HIB strains were identical (capsular type b, biotype I, outer membrane protein subtype 1 and lipopolysaccharide serotype 1) and were beta-lactamase-negative . CONCLUSION: Since it must be assumed that the causative HIB strains circulated in the respective kindergartens and were transmitted to the patients by their healthy siblings, a rifampicin chemoprophylaxis was instituted which included all kindergarten children and their younger siblings . Since the current guidelines on chemoprophylaxis in HIB meningitis do not deal with a situation like the one encountered by us, a revision of the present guidelines was proposed and has been implemented in the meantime. An Esp Pediatr . 1992 Jun;36 Suppl 48:189. New developments in vaccinology; Andre FE; PIP: New vaccine developments will reflect achievements of the World Health Organization's (WHO) Expanded Programme on Immunization (EPI), as well as resistance from the public toward increasing numbers of vaccines . WHO's EPI program has concentrated on tuberculosis, diphtheria, tetanus, whooping cough, polio, and measles . 35 countries are attempting to control hepatitis B with universal vaccination . Now some countries are also recommending vaccination against Haemophilus influenza, mumps, and rubella . The complexity of multiple injections has prompted new research on acellular vaccines for pertussis, hepatitis A and B, varicella, and malaria . Combined vaccines and new adjuvants are also targets of intense research . Vaccines are a priority, because they are among the most cost-effective of medical interventions . Am J Vet Res, 1992 Jun, 53(6), 987 - 94 Comparative virulence of Haemophilus parasuis serovars 1 to 7 in guinea pigs; Rapp-Gabrielson VJ et al.; Reference strains for Haemophilus parasuis serovars 1 to 7 were examined for virulence by inoculation of guinea pigs . Guinea pig response to intraperitoneal inoculation was similar for the 7 reference strains . However, apparent differences in virulence were detected after intratracheal inoculation . Cells of the references strains for serovars 1 and 5 were most invasive, causing moribundity or death at higher doses and a persistent septicemia at lower doses . Haemophilus parasuis could be isolated from respiratory and systemic sites; purulent bronchopneumonia, pericarditis, and pleuritis were apparent in infected guinea pigs . Inoculation of cells of the reference strains for serovars 2 and 6 also resulted in bronchopneumonia and moribundity or death in some guinea pigs; however, reisolation of H parasuis and microscopic lesions at necropsy were less pronounced than those observed with serovars 1 and 5 . Inoculation of cells of serovars 3, 4 and 7 induced only transient clinical signs and minimal evidence of H parasuis infection at necropsy . The data from intratracheal inoculation of guinea pigs are similar to data from other investigations in swine, indicating differences in the pathogenic potential of H parasuis strains . Thus, guinea pigs may be useful as a laboratory animal model for examining cellular factors associated with virulence and immunogenicity of H parasuis. Int J Exp Pathol, 1992 Jun, 73(3), 351 - 7 Effects of microbial stimulation on the number, size and activity of bronchus-associated lymphoid tissue (BALT) structures in the pig; Delventhal S et al.; The development of bronchus-associated lymphoid tissue (BALT) was investigated in the pig, which is a species in which BALT is not found constantly . Different routes of contact with a specifically lung-pathogen bacterium Actinobacillus (Haemophilus) pleuropneumoniae were tested . Pigs, selected by bacteriological screening methods and the number of granulocytes in the bronchoalveolar lavage (BAL), were infected by aerosol . They were compared to previously enterally immunized pigs using active and inactivated bacteria . The development of BALT after the infection was compared to that in pigs with a single enteral, or no, contact with the bacterium . BALT was less frequent in these groups than in the infected pigs . Previously immunized pigs developed the highest number and the largest BALT with the most prominent morphological signs of activation . Immunization with living or inactivated bacteria did not cause histological differences . BALT was preferentially located around bronchioli and small bronchi . Additional BALT predominantly occurred in the walls of larger bronchi . Definite compartments of T and B lymphocytes were not found in immunohistological studies of BALT . It was concluded that the development of BALT can be induced by different modes of microbial stimulation. Clin Infect Dis, 1992 Jun, 14 Suppl 2, S212 - 5; discussion S217 Criteria for evaluation of antimicrobial agents and current therapies for acute sinusitis in children; Giebink GS; Acute sinusitis is a common complication of upper respiratory tract infections in children . The primary causative bacteria are Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, Streptococcus pyogenes, and alpha-hemolytic streptococci . Concurrent viral infection may confound interpretation of the clinical response to antimicrobial treatment . First-line antimicrobial treatment is usually with amoxicillin . The increase in frequency of beta-lactamase-producing bacteria in some communities, however, may warrant empirical treatment with other drugs such as amoxicillin/clavulanate, trimethoprim-sulfamethoxazole, cefixime, or cefuroxime . With the marketing of newer antimicrobial drugs for treating sinusitis, it is important for physicians to understand the criteria for evaluating the efficacy of each new drug in relation to existing antimicrobial agents . Criteria for clinical and bacteriologic evaluation of new antimicrobial drugs in the treatment of sinusitis in children are described. Clin Infect Dis, 1992 Jun, 14 Suppl 2, S204 - 8; discussion S209-11 Comparison of cefprozil with other antibiotic regimens in the treatment of children with acute otitis media; Stutman HR et al.; In two randomized clinical trials in children with otitis media, the efficacy and safety of cefprozil are compared to those of amoxicillin/clavulanate (n = 530) and of cefaclor and cefixime (n = 394) . The rate of clinical cure or improvement was similar among patients receiving each drug regimen, ranging from 78% for amoxicillin/clavulanate to 89% for cefaclor; for cefprozil, this rate was 84% and 85% in the two studies, respectively . In the first study, cefprozil was superior to amoxicillin/clavulanate in the satisfactory clinical response rate for Streptococcus pneumoniae (P = .049), but response rates were similar for Haemophilus influenzae and Moraxella catarrhalis . Significantly more patients treated with amoxicillin/clavulanate (P less than .001) in the first study or cefixime (P less than .01) in the second study developed diarrhea than did those treated with cefprozil . We conclude that cefprozil therapy for otitis media in children produces clinical and bacteriologic response rates similar to those seen with amoxicillin/clavulanate, cefixime, or cefaclor . Furthermore, diarrhea was significantly less common with cefprozil than with cefixime or amoxicillin/clavulanate. Pediatr Infect Dis J, 1992 Jun, 11(6), 466 - 73 Etiology of acute lower respiratory tract infections in children in a rural community in The Gambia; Forgie IM et al.; Approximately 500 children younger than 5 years old resident in 7 villages in a rural area of The Gambia were monitored closely for 1 year for episodes of acute lower respiratory tract infection (ALRI) . Each episode was investigated with antigen detection techniques and antibody assays as well as culture for bacteria and viruses . A pathogen was identified in 76 (34.2%) of 222 cases with clinical signs of ALRI and in 34 (42%) of the 81 cases who, in addition, had radiologic evidence of ALRI . Evidence of infection with a bacterial pathogen, most commonly Streptococcus pneumoniae or Haemophilus influenzae, was obtained in 32 (14.4%) cases with clinical signs of ALRI (23.5% of those with radiologically proved pneumonia) . Viral agents were cultured from 42 (19%) of 221 cases but also from 14 (14.6%) of 96 controls some of whom had minor symptoms of upper respiratory tract infection . In the absence of an outbreak of respiratory syncytial virus the viral agents recovered most often were influenza A and adenoviruses. J Paediatr Child Health, 1992 Jun, 28(3), 249 - 53 A review of therapeutic monitoring of chloramphenicol in patients with Haemophilus influenzae meningitis; Coakley JC et al.; Two hundred and seventy-seven serum chloramphenicol concentrations in 90 patients with Haemophilus influenzae type b meningitis were analysed retrospectively . Most patients were given chloramphenicol 25 mg/kg 6 hourly initially . Chloramphenicol concentrations were categorized as pre-dose ('trough') or post-dose ('peak') . Twenty-six per cent of the results were in the potentially toxic range (above 30 mg/L), and 18% were below 10 mg/L . Analysis of 46 pre- and post-dose measurements showed that for the intravenous (i.v.) route of administration, 23% of the pre-dose concentrations were higher than the corresponding post-dose levels and, for the oral route, 42% of the pre-dose levels were higher . Multivariate analysis of covariance demonstrated that chloramphenicol concentrations decreased significantly with increasing number of days of treatment and that the decline was steeper with i.v . administration . The results of this study emphasize the need for therapeutic monitoring of chloramphenicol concentrations, and suggest that chloramphenicol should be given as a loading dose of 40 mg/kg, followed by 25 mg/kg per dose 8 hourly for 3-4 days and then 6 hourly. J Paediatr Child Health, 1992 Jun, 28(3), 220 - 2 Single daily dose ceftriaxone therapy in epiglottitis; Knight GJ et al.; Ceftriaxone as a single daily intravenous dose for 5 days was used to treat seven patients with proven Haemophilus influenzae epiglottitis . All children responded favourably . The serum levels achieved exceeded the MIC by up to 1500 times at the trough level during and for up to 24 h after the completion of the treatment . Side effects were mild and transient and did not disrupt the continuity of the treatment . Ceftriaxone potentially offers a number of clinical and economic advantages in the management of epiglottitis. Am J Med, 1992 Jun, 92(6), 587 - 90 Haemophilus influenzae type b bacteremia in adults with AIDS and at risk for AIDS; Casadevall A et al.; PURPOSE: Our objective was to determine the number of cases of Haemophilus influenzae type b bacteremia in patients with and at risk for acquired immunodeficiency syndrome (AIDS) from January 1983 to June 1991 at a municipal hospital in Bronx, New York . PATIENTS AND METHODS: We reviewed blood culture records of adult patients admitted to North Central Bronx Hospital from January 1983 to June 1991 to identify cases of bacteremic H . influenzae type b disease . The hospital charts and admission chest radiographs of bacteremic patients were then reviewed . RESULTS: Ten of 15 cases of adult H . influenzae type b bacteremia occurred in patients with AIDS or who were at risk for AIDS . Seven had AIDS at presentation . Nine were active or former intravenous drug users (IVDUs) . All 10 cases were associated with a respiratory source, and five of the 10 patients also had H . influenzae type b isolated from sputum . All H . influenzae type b strains were negative for beta-lactamase . CONCLUSIONS: Human immunodeficiency virus-positive IVDUs may be at increased risk for bacteremic H . influenzae type b infections . Empiric antibiotic regimens for community-acquired pneumonia in these patients should include appropriate antibiotics for the treatment of H . influenzae type b . In addition, these patients may be candidates for conjugate H . influenzae type b vaccine trials. J Trop Med Hyg, 1992 Jun, 95(3), 180 - 5 Childhood bacterial meningitis in Al-Baha province, Saudi Arabia; al-Jurayyan NA et al.; A retrospective review of 71 paediatric patients admitted with bacterial meningitis to the King Fahad Hospital at Al-Baha, Saudi Arabia, during an 8-year period revealed a preponderance of males (67.6%) and young subjects with 88.7% being below 24 months of age . The commonest cerebrospinal fluid pathogens in the series were Haemophilus influenzae type B (HIB), Streptococcus pneumoniae and Group B-beta haemolytic streptococcus, which were responsible for 47.3, 34.5 and 9.1% of cases respectively . Neisseria meningitidis which is a major cause of meningitis in most other reports was uncommon in the present series, and was isolated from only two patients . All the children with Group B-beta haemolytic streptococcal meningitis were below 3 months of age while 96.2% of the children with HIB meningitis were younger than 2 years . Mortality was highest (40%) among the infants with Group B-beta haemolytic streptococcal meningitis . Six (23.1%) of the HIB isolated were resistant to ampicillin and two (7.7%) were resistant to both ampicillin and chloramphenicol . There is a need for greater emphasis on prevention through the use of available vaccines including the newly introduced conjugate vaccines against HIB which are capable of eliciting immune responses in infants as young as 2 months. Pediatrics, 1992 Jun, 89(6 Pt 1), 1019 - 26 Immunization opportunities missed among urban poor children; McConnochie KM et al.; Low immunization rates among US preschool children suggest a need for improved immunization practices . Immunization and encounter records were reviewed to ascertain immunization rates and missed opportunities for vaccine administration among 515 preschool children who were active patients at a hospital-based primary care center serving lower socioeconomic status families in Rochester, NY . The point prevalence at a mean age of 4.4 years for lack of one or more recommended immunizations was 27%; 7% were missing measles-mumps-rubella, 18% were missing Haemophilus influenzae type b, 8% were missing two or more diphtheria-tetanus-pertussis, and 4% were missing two or more oral poliovirus immunizations . A visit was counted as a missed opportunity if an immunization was due but not given . Over the period from birth through age 36 months, 422 (82%) of children missed at least one immunization opportunity . For these 422 children, there was a mean of 7.2 missed opportunities per child . Although 64% of missed opportunities occurred at an acute illness visit, 36% occurred at well-child, administrative, follow-up, or chronic illness visits . Review of 200 medical records randomly selected from all opportunities at acute illness visits found no contraindication in 63% (50% nonfebrile infectious disease, 13% minor noninfectious problems) . Findings for random samples of 100 missed diphtheria-tetanus-pertussis opportunities for children aged 2 to 6 months and 100 missed measles-mumps-rubella opportunities for children 15 to 24 months were similar to findings for the sample of all acute illness visits . Emergency department visits, where immunization records were not readily available, accounted for 18% of missed opportunities.(ABSTRACT TRUNCATED AT 250 WORDS) J Pediatr, 1992 Jun, 120(6), 980 - 6 Loracarbef (LY163892) versus amoxicillin-clavulanate in the treatment of bacterial acute otitis media with effusion; Foshee WS; The efficacy and safety of loracarbef, a new beta-lactam antibiotic, was compared with that of amoxicillin-clavulanate potassium in the treatment of bacterial acute otitis media with effusion . A double-blind format was utilized to administer 10-day, randomized, parallel treatment regimens to patients who were between 6 months and 12 years of age . The most prevalent causative pathogens found in the two treatment groups were Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella (Branhamella) catarrhalis . The percentages of favorable posttherapy clinical responses in evaluable patients were similar for both drugs: 87.3% (124/142) of the loracarbef group, compared with 91.5% (130/142) of the amoxicillin-clavulanate group, showed favorable responses within 72 hours after treatment . Ten to sixteen days after treatment, 68.1% of the loracarbef group, compared with 76.1% of the amoxicillin-clavulanate group, showed favorable responses . More patients in the amoxicillin-clavulanate group reported treatment-emergent events: 46.1% compared with 35.8% in the loracarbef group (p = 0.023) . Diarrhea was the most frequently reported event, occurring in 13.3% of the loracarbef group and in 26.3% of the amoxicillin-clavulanate group (p less than 0.001) . Vomiting was reported by 5.8% of the loracarbef group and 10.3% of the amoxicillin-clavulanate group (p = 0.072) . Loracarbef is comparable in efficacy to amoxicillin-clavulanate in the treatment of bacterial acute otitis media with effusion and has a more desirable safety profile. J Infect Dis, 1992 Jun, 165 Suppl 1, S90 - 2 Molecular biology of phase-variable lipopolysaccharide biosynthesis by Haemophilus influenzae; Maskell DJ et al.; Several chromosomal loci are involved in lipopolysaccharide (LPS) biosynthesis by Haemophilus influenzae . Two of these, lic1 and lic2, contain multiple open-reading frames (ORFs) and include tandem repeats of the tetramer CAAT within and at the 5' end of the coding region of the first ORF in each locus . Variation in the number of repeats of CAAT is involved in the variable expression of LPS epitopes, and genes within these loci are involved in the biosynthesis of these epitopes . lic3 also contains multiple ORFs and the CAAT repeats in the same arrangement as in the other two lic loci . However, in lic3 metabolic functions are encoded by the downstream genes . ORF2 is galE, encoding uridine 5'-diphosphogalactose 4-epimerase, and ORF4 is adk, encoding adenylate kinase . A mutant H . influenzae with a deleted galE gene had an altered LPS when grown on media lacking galactose and was of reduced virulence in infant rats. J Infect Dis, 1992 Jun, 165 Suppl 1, S82 - 5 Bacterial components and the pathophysiology of injury to the blood-brain barrier: does cell wall add to the effects of endotoxin in gram-negative meningitis? Burroughs M, Cabellos C, Prasad S, Tuomanen E. In animal models, the lipopolysaccharide (LPS) from Haemophilus influenzae contributes to all the signs of meningitis associated with living bacteria . However, when tested in vitro, the amount of LPS in cerebrospinal fluid (CSF) in natural disease shows much greater effects on leukocytes than on endothelial permeability . To investigate whether other bacterial components act with LPS to incite meningeal inflammation, animals were challenged intracisternally with H . influenzae lysates . Upon neutralization of endotoxin, leukocytosis was greatly attenuated, but protein accumulation in CSF persisted . Cell wall from H . influenzae induced meningeal inflammation in a pattern opposite to that of LPS . Its ability to induce blood-brain barrier permeability greatly exceeded its ability to induce leukocytosis in vivo . Thus, cell wall, by acting on endothelia, and LPS, by inducing leukocytosis, may cooperate to induce inflammation in H . influenzae meningitis . Optimal reduction of inflammation and tissue damage in meningitis may require agents directed against cell wall as well as LPS. J Infect Dis, 1992 Jun, 165 Suppl 1, S77 - 81 Molecular basis of invasive Haemophilus influenzae type b disease; Moxon ER; The molecular basis of central nervous system invasiveness by Haemophilus influenzae has been studied by using genetically defined mutants and in vivo and in vitro model systems . Capsular polysaccharide and lipopolysaccharide are important microbial determinants of the ability of H . influenzae to traverse the nasopharynx and localize in the cerebrospinal fluid and meninges after bacteremia . The genes for type b capsule confer greater invasive potential than do those for other capsular polysaccharides, although the molecular basis for this is not understood . Mutants have also indicated the role of lipopolysaccharide in enhancing the efficiency of bacterial translocation from the nose to the blood and in facilitating intravascular survival . Organisms that localize successfully in the blood and central nervous system are the progeny of a small fraction of the original challenge inoculum, often a single bacterium. J Infect Dis, 1992 Jun, 165 Suppl 1, S7 - 10 Invasive Haemophilus influenzae type b disease in children less than 5 years of age in Minnesota and in Dallas County, Texas, 1983-1984; Murphy TV et al.; During 1983 and 1984, 733 cases of invasive Haemophilus influenzae type b disease in children less than 5 years of age were identified in Minnesota and in Dallas County, Texas . The overall incidence of disease was lower in Minnesota than in Dallas County . However, among urban residents, the rates of disease for whites were similar in the two areas . A higher rate of disease among whites in urban Minnesota compared with rural Minnesota resulted from an increased rate of cases for diagnoses other than meningitis . Local practices might have affected the rate of certain diagnoses, since ascertainment of Hib disease other than meningitis is more dependent on diagnostic practices than is diagnosis of meningitis . These data suggest that the incidence of invasive H . influenzae type b disease is influenced by the racial composition of the population, the rates of disease in specific subgroups, and possibly by local medical practices . Understanding the factors that contribute to the incidence of disease is necessary to interpret variations in different populations and changes over time. J Infect Dis, 1992 Jun, 165 Suppl 1, S66 - 9 G2m(23) immunoglobulin allotype and immunity to Haemophilus influenzae type b; Granoff DM et al.; G2m(23), an allotype on IgG2 molecules, is detected in sera of about two of three Caucasians . Adults who are homozygous for G2m(23) have IgG2 antibody responses to types 14 and 18C pneumococcal polysaccharides fourfold higher than those of homozygous-negative subjects . Adults homozygous for G2m(23) also show higher IgG2 antibody responses to vaccination with Haemophilus influenzae type b (Hib) polysaccharide . Furthermore, adults heterozygous for G2m(23) show IgG2 antibody responses intermediate between responses of those homozygous-positive and homozygous-negative . In contrast, the magnitude of the IgG1 antibody responses of adults to Hib polysaccharide was similar irrespective of G2m(23) genotype status . The magnitude of the IgG antibody responses of children vaccinated with Hib polysaccharide is not affected by G2m(23) status, in part because the IgG subclass responses of children to this antigen are restricted to IgG1 . Also, children show no consistent associations between G2m(23) allotype status and the risk of acquiring Hib disease or the risk of Hib vaccination failure. J Infect Dis, 1992 Jun, 165 Suppl 1, S62 - 5 The role of complement in the host's defense against Haemophilus influenzae; Winkelstein JA et al.; In vitro studies have shown that Haemophilus influenzae type b (Hib) can activate both the classical and alternative pathways of complement and generate complement-dependent opsonic and bactericidal activities . In vivo studies and observations in complement-deficient patients have established the biologic significance of complement in the host's defense against H . influenzae . The complement system plays a significant role in the host's defense against Hib and against other encapsulated and unencapsulated H . influenzae, mainly by enhancing clearance from the bloodstream through its action as an opsonin in both nonimmune and immune hosts . Patients with genetically determined deficiencies of C3 or of the complement components involved in C3 activation have an increased susceptibility to H . influenzae . More recently, a relatively common deficiency of one isotype of C4 (C4B) has been shown to be associated with invasive Hib disease, suggesting that defects in complement-mediated host defense may be more common in systemic Hib infections than previously appreciated. J Infect Dis, 1992 Jun, 165 Suppl 1, S57 - 61 Immunoglobulin variable region gene expression in response to Haemophilus influenzae type b polysaccharide; Carroll WL et al.; The mechanism(s) responsible for the ontogenic patterns of acquisition of the antibody repertoire is unknown . The immune response to Haemophilus influenzae type b (Hib) capsular polysaccharide provides an excellent model system in which to examine the ontogeny of immunoglobulin variable region expression . A panel of hybridomas secreting human antibodies specific for Hib capsular polysaccharide was developed using peripheral blood lymphocytes from donors immunized with Hib vaccines . Nucleotide sequence analysis of the heavy chain V regions expressed by four of these hybridomas suggests selective use of members of the VHIII gene family in combination with different D and J segments . The nucleotide sequences were highly homologous to two candidate germline gene sequences . Others have reported that these particular germline sequences are expressed in fetal liver, suggesting that the inability of young children to produce antibody to the Hib capsular polysaccharide is not due to failure to express these VH regions early in ontogeny. J Infect Dis, 1992 Jun, 165 Suppl 1, S29 - 32 A prospective, population-based study of Haemophilus influenzae type b meningitis in The Gambia and the possible consequences; Bijlmer HA et al.; A prospective population-based field study on Haemophilus influenzae type b (Hib) meningitis was carried out in The Gambia, West Africa . The annual incidence was 60 cases/100,000 children less than 5 years old and 297 cases/100,000 less than 1 year . The peak incidence was in those 5 months old, and 45% of cases occurred in those less than 6 months . The case fatality rate was 37% . Because the outcome did not appear to be affected by the logistics of receiving care, and resistance to chloramphenicol and ampicillin is not yet a problem, prevention of Hib disease at an early age seems the best solution . There are several options for vaccine trials . On the basis of available data, at least one of these trials seems warranted before Hib vaccination can be introduced in developing countries . Extrapolation of successful results in industrialized countries to a population of different genetic origin and living under different conditions seems questionable. J Infect Dis, 1992 Jun, 165 Suppl 1, S26 - 8 Epidemiology of acute lower respiratory tract infections, especially those due to Haemophilus influenzae type b, in The Gambia, west Africa; Greenwood B; Mortality surveys undertaken in rural areas of The Gambia, a small country on the west coast of Africa, indicate that acute lower respiratory tract infections (ALRI) are the most frequent cause of death among children and that approximately 1 in 25 rural Gambian children dies from an ALRI before the age of 5 years . Community surveys suggest that each child experiences an average of one episode of ALRI accompanied by radiographic changes before reaching this age . Etiologic studies have shown that pneumococci, Haemophilus influenzae type b (Hib), and respiratory syncytial virus are the most important causes of ALRI in Gambian children who present to a hospital, and the same three organisms are probably the major causes of severe ALRI in rural communities . Hib probably accounts for 5%-10% of cases of severe ALRI in Gambian children, and because the incidence of severe ALRI is high, an effective Hib conjugate vaccine might save as many childhood deaths by preventing pneumonia as by preventing meningitis. J Infect Dis, 1992 Jun, 165 Suppl 1, S20 - 5 Epidemiology of acute respiratory tract infections, especially those due to Haemophilus influenzae, in Papua New Guinean children; Lehmann D; Acute lower respiratory tract infections (ALRI) are the most common cause of death in Papua New Guinean children . Haemophilus influenzae and Streptococcus pneumoniae are almost universally carried in the nasopharynx from a young age and commonly cause disease . While most H . influenzae isolates from blood and cerebrospinal fluid are serotype b, other serotypeable and nonserotypeable H . influenzae are more frequently isolated in Papua New Guinea than in developed countries . Low levels of antipneumococcal antibody, malnutrition, and upper respiratory carriage of invasive pneumococcal serotypes are associated with increased risk of ALRI . An oral H . influenzae vaccine given to adults with chronic bronchitis reduced the bacterial load in sputum and may thereby help reduce transmission of bacteria in the community . The efficacy of conjugate H . influenzae type b vaccine in preventing pneumonia must be determined in developing countries; vaccines against other types of H . influenzae will also be needed to control pneumonia and meningitis. J Infect Dis, 1992 Jun, 165 Suppl 1, S2 - 6 Epidemiology of invasive Haemophilus influenzae type b disease; Makela PH et al.; Invasive disease caused by Haemophilus influenzae type b (Hib) is typically a disease of young children, starting when the protection afforded by maternal antibodies is exhausted and ending when the child's own antibody production to the Hib capsular polysaccharide begins efficiently . There are, however, large variations between population groups in the incidence of the disease and the age at which it appears . Potential factors behind this variation include virulence genes of the bacteria and genetic susceptibility genes of the host . Although such genes and their effects can be identified, their impact on the disease's incidence is only minor . Potentially much more important appear to be socioeconomic factors that to a large extent determine the exposure of the child to Hib and to other infectious agents that may enhance both colonization and invasive infection by Hib. J Infect Dis, 1992 Jun, 165 Suppl 1, S185 - 7 Animal models for the study of noninvasive Haemophilus influenzae disease: pulmonary clearance systems; Hansen EJ et al.; Nontypeable Haemophilus influenzae are increasingly being recognized as an important cause of disease in the lower respiratory tract . Information about the pathogenesis of these infections has been limited until recently by the paucity of experimental animal models for studying the host-parasite interaction in vivo . Three different animal models for investigation of the interaction of nontypeable H . influenzae with the lower respiratory tract have been used: Two involve the evaluation of short-term pulmonary clearance in mice or rats, while a new, long-term infection model in rats mimics the more chronic bronchopulmonary infections sometimes caused by these organisms . Results obtained in these three model systems indicate that both humoral and cellular immune mechanisms are involved in immunity to lower respiratory tract disease due to nontypeable H . influenzae. J Infect Dis, 1992 Jun, 165 Suppl 1, S181 - 4 Outer membrane proteins and lipopolysaccharides of nontypeable Haemophilus influenzae; Barenkamp SJ; Several outer membrane proteins of nontypeable Haemophilus influenzae are potential vaccine candidates: P2 and P6 elicit antibodies that are bactericidal and protective in experimental models of infection . Other proteins are being investigated . A group of surface-exposed high-molecular-weight proteins that are major targets of antibody in human convalescent sera were identified . Monoclonal antibodies to the high-molecular-weight proteins of a prototype strain recognized two distinct but related proteins and were bactericidal for the prototype strain and other strains that shared the epitope recognized by the monoclonals . Genes encoding the two proteins in the prototype strain recognized by the monoclonals were cloned and sequenced . The sequences were distinct but related, and the derived amino acid sequences had sequence similarity to that of filamentous hemagglutinin of Bordetella pertussis, an important adherence factor and protective antigen. J Infect Dis, 1992 Jun, 165 Suppl 1, S177 - 80 Epidemiology and prevention of respiratory tract infections due to nonencapsulated Haemophilus influenzae; van Alphen L; Nonencapsulated Haemophilus influenzae cause mainly respiratory tract infections, including otitis, sinusitis, and pneumonia . These infections may become chronic or recurrent in patients with bronchitis or otitis . Patients are usually infected with one strain at a time . During recurrent otitis, H . influenzae isolates have an outer membrane protein composition different from that seen during earlier episodes . In chronic bronchitis, H . influenzae strains persist for up to 1 year . In addition, isolates with different outer membrane protein compositions have been obtained that are antigenic variants of previous isolates . The variations occur in outer membrane protein b,c (P2), d (P5), or both . The variable parts are immunodominant, and antibodies to these parts are bactericidal . Cross-reactive bactericidal antibodies to outer membrane proteins have been elicited in immunized animals . These data indicate that natural immunity to nonencapsulated H . influenzae is mainly strain-specific but also that biologically active cross-reactive antibodies can be elicited by immunization. J Infect Dis, 1992 Jun, 165 Suppl 1, S167 - 76 Humoral immune response patterns of human mucosae: induction and relation to bacterial respiratory tract infections; Brandtzaeg P; Immunoglobulin-producing cells in mucosal tissues, quantitatively the body's most important humoral immune system, synthesize mainly dimers and larger polymers of IgA (poly-IgA) with incorporated J (joining) chain . Poly-IgA is actively transported to exocrine secretions by a transmembrane epithelial glycoprotein called secretory component . Enhancing secretory immunity by oral vaccination is an interesting possibility, but mucosal antigen uptake and local immune regulation are complex and only partly understood . Immunoglobulin isotype response patterns in the upper respiratory mucosa and distal gut are strikingly different . The preferential production of IgA1 in nasal and bronchial mucosae is intriguing in view of the frequent synthesis of IgA1-specific proteases by Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis . A relationship of proneness to produce invasive disease and enzymatically induced deterioration of secretory immunity has been proposed . Differences in mucosal immune response patterns among patients with selective IgA deficiency or IgG subclass deficiencies also suggest that local humoral immunity is an important variable in resistance to infections. J Infect Dis, 1992 Jun, 165 Suppl 1, S16 - 9 Brazilian purpuric fever identified in a new region of Brazil . The Brazilian Purpuric Fever Study Group; Preparation et al.; Laboratory of Bacterial Vaccines, National Institute of Public Health and Environmental Protection, Bilthoven, NetherlandsSynthetically prepared ribosylribitol phosphate dimer and trimer analogous to fragments of the capsular polysaccharide of Haemophilus influenzae type b, containing either an amino- or a (masked) thiol-functionalized spacer, were conjugated to protein by two different methods . The thiol-containing carbohydrates were conjugated to tetanus toxoid or H . influenzae outer membrane protein using N-succinimidyl 3-(2-pyridyldithio)propionate . Glutaric dialdehyde was used to conjugate the amino-containing carbohydrates with tetanus toxoid . All conjugates were able to bind antibodies raised against the native bacterial polysaccharide, as determined by competition ELISA . The glutaric dialdehyde conjugate prepared from ribosylribitol phosphate trimer and tetanus toxoid induced a strong polysaccharide-specific antibody response in mice and rabbits. J Infect Dis, 1992 Jun, 165 Suppl 1, S144 - 51 Prevention of Haemophilus influenzae type b infections in Apache and Navajo children; Santosham M et al.; Prospective surveillance of Haemophilus influenzae type b (Hib) disease has been done since 1981 in two high-risk populations, White Mountain Apaches and Navajos . The attack rate in children less than 5 years of age is 5-10 times higher than in the general US population . Three vaccines were evaluated . Unconjugated Hib capsular polysaccharide produced lower antibody responses in 18- and 24-month-old Apache infants than in white infants . HbOC (Hib oligosaccharide covalently linked to the nontoxic mutant diphtheria toxin CRM197) produced low antibody responses in Navajo infants after one or two doses but induced responses similar to those in whites after three doses . The responses of 18-month-old Navajos to HbOC were lower than those of whites, but most achieved protective levels . PRP-OMP (Hib capsular polysaccharide linked to the outer membrane protein complex of Neisseria meningitidis) produced good immune responses in 2-month-old Navajo and Apache infants after a single dose . This vaccine was greater than 90% efficacious in protecting Navajo infants from Hib disease when given at 2 and 4 months of age . Even a single dose achieved a high protective efficacy. J Infect Dis, 1992 Jun, 165 Suppl 1, S139 - 43 Safety, immunogenicity, and efficacy in infancy of oligosaccharide conjugate Haemophilus influenzae type b vaccine in a United States population: possible implications for optimal use; Black SB et al.; Between February 1988 and June 1990, the safety, immunogenicity, and efficacy of Haemophilus influenzae type b (Hib) oligosaccharide conjugate (HbOC) vaccine was evaluated in a prelicensure trial of 61,080 children . HbOC was found to be safe and immunogenic in infancy . Extended follow-up revealed that as of 31 December 1990, 30 cases of invasive Hib disease had occurred in 74,699 children; 26 were in unvaccinated children and 4 in children who had received only one dose . No disease occurred in children who had received two or three doses . By 30 September 1991, another case had occurred in an unvaccinated child . Comparison of these efficacy data with those of Hib capsular polysaccharide-outer membrane protein conjugate vaccine (PRP-OMP) reveals that both were effective in preventing disease in the first year of life . However, the small cohort in the PRP-OMP study did not allow demonstration of duration of protection beyond 1 year . Ongoing surveillance in larger populations is necessary to allow comparison of the duration of immunity provided by these vaccines. J Infect Dis, 1992 Jun, 165 Suppl 1, S137 - 8 Finnish efficacy trials with Haemophilus influenzae type b vaccines; Eskola J et al.; The first Finnish trial with Haemophilus influenzae type b vaccine was conducted during 1973-1974 . It demonstrated that the polysaccharide vaccine was 90% efficacious in children greater than or equal to 18-24 months old . The immunologically superior polysaccharide-protein conjugate vaccines have been used since 1986 in randomized trials . The PRP-D vaccine (polysaccharide conjugated to diphtheria toxoid) was 90% efficacious when given at 3, 4, and 6 months of age to 58,000 infants . In 1988-1989, the PRP-D vaccine was compared with the HbOC vaccine (oligosaccharide conjugated to CRM197 protein) . Follow-up is continuing, but both vaccines seem to be efficacious after two doses in infancy. J Infect Dis, 1992 Jun, 165 Suppl 1, S134 - 6 Maternal immunization with the capsular polysaccharide vaccine for Haemophilus influenzae type b; Glezen WP et al.; Maternal immunization with the capsular polysaccharide (PRP) vaccine of Haemophilus influenzae type b has been shown to extend the time that protective levels of maternal antibody are detected in infants . In a randomized, blinded trial, PRP or placebo was administered uneventfully to 213 women in the third trimester of pregnancy . Infants born to PRP recipients had significantly higher levels of antibody to PRP than did infants born to placebo recipients: 2.73 micrograms/ml compared with 0.33 microgram/ml . It was estimated that infants of mothers who received the PRP vaccine would be protected for an average of 4 months compared to an average of only 2 months for those of mothers who received placebo . Infants were followed for invasive H . influenzae type b disease through the first year of life; none was detected. J Infect Dis, 1992 Jun, 165 Suppl 1, S129 - 33 Evaluation of bacterial polysaccharide immune globulin for the treatment or prevention of Haemophilus influenzae type b and pneumococcal disease; Siber GR et al.; A human hyperimmune globulin termed bacterial polysaccharide immune globulin (BPIG) has been prepared from plasma donors immunized with Haemophilus influenzae type b (Hib), pneumococcal, and meningococcal vaccines . At a dose of 0.5 ml/kg, BPIG increased levels of antibody to Hib by greater than 0.15 microgram/ml within 4-6 h and by 2-4 micrograms/ml at 72 h . Thereafter, antibody declined, with a mean half-life of 27 days . BPIG treatment of Apache infants did not impair their active antibody responses to concurrently administered diphtheria-tetanus-pertussis or Hib oligosaccharide-diptheria CRM197 conjugate vaccines . In high-risk Apache infants, BPIG given at 2, 6, and 10 months of age provided significant protection from invasive Hib infection during infancy . Thus, BPIG may have utility in the prevention of Hib infections in high-risk patients who cannot be immunized adequately with Hib conjugate vaccines. J Infect Dis, 1992 Jun, 165 Suppl 1, S121 - 8 The biology of Haemophilus influenzae type b vaccination failure; Holmes SJ et al.; Vaccination with unconjugated polysaccharide vaccine against Haemophilus influenzae type b (Hib) disease at a median age of 25 months was not effective in a group of children who developed Hib disease at a median age of 35 months . This group had normal serum immunoglobulin concentrations but impaired anticapsular antibody responses to Hib infection and to reimmunization with unconjugated polysaccharide . Another group vaccinated with conjugated polysaccharide vaccine at a median age of 18 months developed Hib disease at a median age of 24 months . Of this group, 40% had subnormal immunoglobulin concentrations, particularly IgG2, and showed impaired antibody responses to Hib infection, whereas those with normal immunoglobulin concentrations showed high antibody responses to Hib infection . In both vaccination failure groups, low antibody responders to infection responded to revaccination with Hib conjugate, and most children expressed the idiotype HibId-1 in convalescent or postrevaccination sera . The presence of this idiotype implies that vaccination failure did not result from an inability to use the V kappa II A2 variable region gene, which is used in the anticapsular antibody response of most healthy children. J Infect Dis, 1992 Jun, 165 Suppl 1, S11 - 5 Socioeconomic risk factors for invasive Haemophilus influenzae type b disease; Takala AK et al.; Socioeconomic risk factors for primary invasive Haemophilus influenzae type b (Hib) disease include factors that increase exposure to Hib (day care attendance, presence of siblings, and crowded households) and factors that increase an individual's susceptibility to Hib infections (short duration of breast feeding, parental smoking, and frequent infections in general) . These factors are consistently found to be associated with risk of Hib disease in studies conducted in populations that differ in their Hib disease epidemiology . However, there are large differences in the prevalence of these risk factors among populations . According to present knowledge, variations in the prevalence of socioeconomic risk factors may explain most of the differences in the epidemiology of Hib disease and may also contribute to the differences in Hib vaccine efficacy in different populations. J Infect Dis, 1992 Jun, 165 Suppl 1, S103 - 4 Iron acquisition in Haemophilus influenzae: receptors for human transferrin; Schryvers AB et al.; As an adaptation to the iron-limited environment of the host, Haemophilus influenzae has a transferrin receptor-mediated mechanism of iron acquisition such that it can acquire iron directly from human transferrin . The absence of detectable siderophore production and the presence of transferrin binding in a collection of type b and nontypeable H . influenzae strains indicate that the mechanism is widespread in this species . Growth and binding studies have consistently shown that the receptor is specific for human transferrin, which correlates with the host range of this pathogen . Inhibitor experiments indicate that iron regulation of receptor activity is mediated at the gene level . Affinity isolation experiments indicate that, as observed with other bacterial pathogens, the receptor is composed of two iron-repressible outer membrane proteins, transferrin binding proteins 1 and 2. J Infect Dis, 1992 Jun, 165 Suppl 1, S100 - 2 Interaction of Haemophilus influenzae with mucus, cilia, and respiratory epithelium; Wilson R et al.; One nontypeable laboratory strain and five nontypeable clinical isolates of Haemophilus influenzae from sputum were investigated . Bacteria replicated from 10(4) to 10(8) cfu/ml over 24 h in an organ culture of human respiratory mucosa with only the intact mucosal surface exposed . By transmission electron microscopy, bacteria were not seen in association with normal respiratory epithelium, even after incubation for 24 h . H . influenzae infection caused patchy and occasionally confluent damage to epithelium, and the bacteria associated only with structurally damaged cells . Scanning electron microscopy revealed increased mucus, and slowed ciliary beat frequency was measured by photometry . Fimbriation of H . influenzae increased buccal cell adherence but did not facilitate association with normal or damaged respiratory epithelium or increase epithelial damage, indicating that adhesins other than fimbriae are present . Interactions with mucus, cilia, and epithelium are likely to be important in the pathogenesis of H . influenzae respiratory infections. Infect Immun, 1992 Jun, 60(6), 2391 - 6 Common antigenic domains in transferrin-binding protein 2 of Neisseria meningitidis, Neisseria gonorrhoeae, and Haemophilus influenzae type b; Stevenson P et al.; There is now considerable evidence to show that in the Neisseria and Haemophilus species, membrane receptors specific for either transferrin or lactoferrin are involved in the acquisition of iron from these glycoproteins . In Neisseria meningitidis, the transferrin receptor appears to consist of two proteins, one of which (TBP 1) has an M(r) of 95,000 and the other of which (TBP 2) has an M(r) ranging from 68,000 to 85,000, depending on the strain; TBP 2 binds transferrin after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electroblotting, but TBP 1 does not do so . The relative contributions of these two proteins to the binding reaction observed with intact cells and to iron uptake are presently unknown . However, they are being considered as potential components of a group B meningococcal vaccine . Analogous higher- and lower-molecular-weight proteins associated with transferrin binding have been found in N . gonorrhoeae and Haemophilus influenzae . Previous work with polyclonal antibodies raised in mice with whole cells of iron-restricted N . meningitidis showed that the meningococcal TBP 2 exhibits considerable antigenic heterogeneity . Here, we report that antiserum against purified TBP 2 from one strain of N . meningitidis cross-reacts on immunoblotting with the TBP 2 of all meningococcal isolates examined, as well as with the TBP 2 of N . gonorrhoeae . This antiserum also cross-reacted with the TBP 2 of several strains of H . influenzae type b, thus showing the presence of common antigenic domains among these functionally equivalent proteins in different pathogens; no cross-reaction was detected with a purified sample of the human transferrin receptor. J Infect Dis, 1992 Jun, 165(6), 1148 - 50 Abundant attachment of bacteria to nasopharyngeal epithelium in otitis-prone children; Stenfors LE et al.; Attachment of bacteria to nonciliated cells of the nasopharyngeal epithelium was evaluated by immunofluorescence assay in 25 otitis-prone and 25 non-otitis-prone children undergoing ear, nose, or throat surgery under general anesthesia . The bacterial findings were analyzed simultaneously, both qualitatively and quantitatively . In otitis-prone children, there was a significant preponderance of epithelial cells having greater than 50 attached bacteria (P less than .001) and of epithelial cells with attached Streptococcus pneumoniae and Haemophilus influenzae (P less than .05) . Also, the occurrence of Branhamella catarrhalis in the nasopharynx was more pronounced in the otitis-prone group (P less than .05) . No significant differences in the occurrence of other middle ear pathogens or quantitative dominance of pathogens were noted between the two groups . Abundant attachment of pathogens to the epithelial cells close to the nasopharyngeal orifice of the eustachian tube is of a significant factor for the development of the otitis-prone condition. J Infect Dis, 1992 Jun, 165(6), 1069 - 75 Molecular epidemiology of unrelated clusters of multiresistant strains of Haemophilus influenzae; Dimopoulou ID et al.; Three epidemiologically unrelated clusters of Haemophilus influenzae resistant to ampicillin, chloramphenicol, and tetracycline were studied . The biotypes and cell-envelope protein patterns were determined for 17 nonencapsulated strains, 6 from Dundee and 11 from Cheltenham, and for 6 type b encapsulated strains from Guildford . After mobilization by conjugation, large 32- to 36-MDa plasmids were purified from all the strains . The restriction fragment patterns of the plasmids were determined by ethidium bromide staining of digested purified plasmid or by Southern hybridization of digested total cellular DNA of the parent strains, probed with purified plasmid . Evidence is presented for a chromosomal location of the plasmids in the parent strains, the spread in nature of a plasmid between distinguishable strains of H . influenzae, the person-to-person spread of a strain within a cluster, and a high degree of sequence homology between distinguishable plasmids, implying their close relatedness. J Gen Microbiol, 1992 Jun, 138 ( Pt 6), 1185 - 96 Distinct plasmid profiles of Pasteurella haemolytica serotypes and the characterization and amplification in Escherichia coli of ampicillin-resistance plasmids encoding ROB-1 beta-lactamase; Azad AK et al.; Thirty-five isolates of Pasteurella haemolytica from cattle or sheep were screened for the presence of plasmids and for resistance to a range of antibiotics . Eight strains (four of serotype A1, three of serotype A2 and one untypable) contained plasmid DNA and isolates of the same serotype had similar plasmid profiles, which were different from those of the other serotypes . All but one of the plasmid-bearing strains were isolated from pneumonic animals or from animals in contact with pneumonic cattle or sheep . In A2 and untypable strains, there was no obvious correlation between antibiotic resistance and the presence of a specific plasmid . In contrast, all plasmid-bearing A1 strains exhibited ampicillin resistance (ApR), which was shown by transfer studies to be plasmid-mediated . Plasmid DNA prepared from E . coli transformants was not routinely detected on ethidium-bromide-stained agarose gels, but could be amplified to detectable levels by treatment of cultures with chloramphenicol (Cm) or by modifying the growth conditions . The ApR plasmids from P . haemolytica were identical by restriction enzyme analysis . Restriction analysis and hybridization data indicated that these plasmids were closely related to the prototype ROB-1 beta-lactamase-encoding plasmid, originally isolated from Haemophilus influenzae . From substrate profiles and isoelectric focusing data, the beta-lactamases encoded by the P . haemolytica plasmids were indistinguishable from the ROB-1 beta-lactamase. Eur J Clin Microbiol Infect Dis, 1992 Jun, 11(6), 546 - 9 Evaluation of four commercial methods for identification and biotyping of genital and neonatal strains of Haemophilus species; Quentin R et al.; Four commercial methods for identification of Haemophilus species were evaluated in comparison to conventional methods using 188 genital and neonatal Haemophilus strains . In the case of discrepancies between results obtained by the different methods, DNA-DNA hybridization was performed . The four commercial systems and conventional methods showed excellent correlation of results in 167 strains (88%) . DNA-DNA hybridization was performed in 8 strains with discrepant identification results and 13 strains with discrepant biotyping results . In 15 cases discrepancies could be explained by the fact that the strains belonged to a newly recognised species of Haemophilus. Microb Pathog, 1992 Jun, 12(6), 433 - 42 Epitope analysis of an immunodominant domain on the P1 protein of Haemophilus influenzae type b using synthetic peptides and anti-idiotypic antibodies; Proulx C et al.; Synthetic peptides, anti-idiotypic antibodies (anti-Id) and human and murine monoclonal antibodies (mAbs) were used to further define a major antigenic domain on the outer membrane P1 protein (OMP) of Haemophilus influenzae type b (Hib) . Synthetic peptides were elaborated from the known primary sequences of the P1 protein of prototype Hib strains MinnA (OMP subtype 1H) and 8358 (OMP subtype 6U) . By peptide mapping, antibodies are categorized into three groups: A, B and C . A first epitope on the P1 from strain MinnA was identified by the reactivity of one set of murine anti-P1 mAbs with the two overlapping peptides 11H and 13H, corresponding to amino acid residues 384-412 and 400-437, respectively . On the basis of their reactivity with both peptides, these mAbs were designated as group A . Anti-Id obtained from mice immunized with two group A mAbs reacted specifically with all group A mAbs . A second epitope on the same P1 protein was identified by the reactivity of the peptide 13H with another distinct set of murine anti-P1 mAbs assigned to group B . This group of mAbs did not recognize the peptide 11H . Murine anti-Id which were prepared against one group B mAb inhibited the attachment of this mAb to outer membrane preparations, whereas the binding of the other group B mAbs was not affected, suggesting that these mAbs represent a heterologous group of mAbs . The epitope(s) recognized by two human anti-P1 mAbs was (were) distinct from the ones recognized by murine mAbs since no reactivity with the peptides was observed . Similarly, the binding of the two human mAbs to the P1 antigen was not inhibited by anti-Id raised against group A or B mAbs . Interestingly, an epitope on a different P1 protein recovered from strain 8358 was identified by the reactivity of group C murine mAbs with the peptide 13U, which occupies the same position on the P1 protein as 13H but differs from the latter by 10 amino acid residues . Our studies demonstrated the presence of several distinct surface-exposed B-cell epitopes within the antigenic domain which was defined previously on the P1 protein of Hib MinnA . Furthermore, we showed the immunodominance of this region on two different P1 proteins . None of the mAbs, however, had a bacteriolytic or protective activity against Hib strains . We suggest that the surface-exposed immunodominant region on the OMP P1 of Hib do not induce protective antibodies against Hib infection. Zentralbl Bakteriol, 1992 Jun, 277(1), 34 - 8 Lack of immunoglobulin A1 protease production by Haemophilus ducreyi; Abeck D et al.; A collection of 20 strains of Haemophilus ducreyi including freshly isolated, low-passage and multi-passage reference strains was examined for immunoglobulin A1 protease production by SDS-PAGE and immunoblotting . None of the strains demonstrated IgA1 protease activity despite the fact that different culture media were used . By direct immunofluorescence testing, binding of IgA to Haemophilus ducreyi organisms could be demonstrated. Jpn J Antibiot, 1992 Jun, 45(6), 744 - 55 {Bacteriological and clinical studies on meropenem in the pediatric field}; Akita H et al.; Bacteriological and clinical studies have been performed on meropenem (MEPM, SM-7338), a newly developed carbapenem antibiotic, in the pediatric field . 1 . Antibacterial activities of MEPM against 24 clinical isolates were determined . MEPM showed excellent activity against Gram-positive bacteria including Staphylococcus aureus and Gram-negative bacteria, especially Escherichia coli and Branhamella catarrhalis . Against Haemophilus influenzae, MEPM had a higher activity than imipenem and flomoxef, but had a lower activity than piperacillin and cefoperazone . 2 . Clinical efficacies of MEPM were evaluated in 32 cases with bacterial infections . A poor efficacy was observed in 1 patient with phlegmon but excellent or good efficacies were obtained in other 31 patients with tonsillitis (1), pneumonia (17), UTI (12), or SSSS (1) . The overall efficacy rate was 96.9% . All strains except 1 of S . aureus were eradicated by the administration of MEPM, and a high eradication rate of 95.8% (23 out of 24 strains) was obtained . 3 . No side effects were observed in 35 evaluated cases . As abnormal laboratory test results, elevated GOT, elevated GPT, eosinophilia and neutropenia were noted in 4, 4, 4 and 2 patients, respectively . 4 . Influences on blood coagulation parameters were studied . PIVKA II was elevated upon administration of MEPM in some cases, but no changes in ATT, TT, HPT or Fbg were observed during the treatment . Based on the above results, it has been concluded that MEPM is a safe and effective drug to use in the treatment of pediatric infections . The usual recommended dosage and administration should be 10 to 20 mg/kg of MEPM at a time, using intravenous drip infusion, 3 times a day. Jpn J Antibiot, 1992 Jun, 45(6), 697 - 717 {Pharmacokinetic and clinical studies with meropenem in the pediatric field . Pediatric Study Group of Meropenem}; Fujii R et al.; Pharmacokinetic and clinical evaluations in pediatrics were made on meropenem (SM-7338, MEPM), a new parenteral dehydropeptidase-1 stable carbapenem used without any inhibitors, at 33 medical institutions . The results are summarized as follows . 1 . Pharmacokinetic studies . MEPM at a dose of 10, 20, or 40 mg/kg was administered to 53 children by 30-minute drip infusion . Peak plasma concentrations (Cmax's) and plasma half-lives (T1/2's) of these doses were 28.5, 47.2 and 130.0 micrograms/ml, and 0.80, 0.93 and 0.94 hours, respectively . A clear dose response was observed in Cmax's and T1/2 values were quite similar to those observed in adults . In the first 6 hours after administration, 54.4 to 68.1% of the administered drug was recovered in urine . The cerebrospinal fluid (CSF) levels of MEPM in patients with purulent meningitis were 0.13 microgram/ml at a dose of 6 mg/kg, and 0.64 to 4.22 micrograms/ml at a dose of 29 to 44 mg/kg within day 4 of onset . The penetration rate of MEPM showed an intermediate value among those for other cephalosporin antibiotics . 2 . Clinical study . Clinical efficacies of MEPM were evaluated in 389 cases . The most common doses used were 10 to 20 mg/kg/once, 2 to 3 times a day . The maximum dose was 173 mg/kg/day q.i.d . MEPM gave "excellent" or "good" responses in 242 (97.6%) out of 248 cases in which causative organisms were documented and in 134 (95.0%) out of 141 cases in which causative organisms were not identified . Clinical efficacy rates were 100% in 11 patients with purulent meningitis, 85.7% in 7 with septicemia, 98.8% in 173 with pneumonia, and 100% in 65 with UTI . Bacteriologically, 260 strains (96.7%) out of 269 strains were eradicated by MEPM treatment . Eradication rates were 89.2% for Staphylococcus aureus (37 strains) and 100% for Streptococcus pneumoniae (35 strains) . The overall eradication rate for Gram-positive bacteria was 94.6% . Among Gram-negative bacteria, 98.3% out of 172 strains were eradicated . The eradication rate of Haemophilus influenzae (73 strains) was 98.6% and Pseudomonas aeruginosa (11 strains) was 90.9%, and all of Branhamella catarrhalis (15 strains), Escherichia coli (42 strains), and Klebsiella pneumoniae (6 strains) were eradicated . Out of 84 cases for which previous antibiotic therapies of 3 days or longer were not successful, MEPM gave "excellent" or "good" responses in 77 cases (91.7%) and excellent bacteriological responses (95.7%).(ABSTRACT TRUNCATED AT 400 WORDS) Clin Otolaryngol, 1992 Jun, 17(3), 208 - 10 Post-tonsillectomy bacteraemia; Gaffney RJ et al.; Post-tonsillectomy bacteraemia is a well recognized aetiological factor in streptococcal endocarditis . Prophylactic penicillin has been recommended to reduce its incidence in susceptible patients undergoing tonsillectomy . Recent studies have shown a change in the microflora and an increase in the number of penicillin resistant organisms in the tonsils of patients undergoing tonsillectomy . The aim of this study has been to assess the incidence of post-tonsillectomy bacteraemia, identify the organisms associated with it and review the suitability of penicillin in prophylactic regimens . Of the 32 patients included in the study, 11 (34.4%) had positive post-tonsillectomy blood cultures . We were surprised at this low incidence of bacteraemia and have postulated a possible reason . Haemophilus influenzae was isolated from 4 (36.4%) of the positive cultures and Streptococcus viridans in only 1 (9%) . Rather than using penicillin for prophylaxis a beta-lactamase stable antibiotic would be more appropriate. Clin Otolaryngol, 1992 Jun, 17(3), 195 - 9 Occurrence of Streptococcus pneumoniae and Haemophilus influenzae in otitis media with effusion; Stenfors LE et al.; Eighty mucoid effusion samples obtained from 56 patients with otitis media with effusion (OME) were subjected to quantitative and qualitative bacteriological analysis using standard culturing methods, direct microscopy and immunofluorescent assay . 30% of the samples contained culture-positive pathogens (H . influenzae, S . pneumoniae, B . catarrhalis), with counts never exceeding 5 x 10(5) per ml . In addition, 19% of the samples had dormant H . influenzae and S . pneumoniae, which did not grow on standard agar plates . Viable and dormant bacteria, as well as bacterial remnants, play a crucial role in the pathogenesis of OME and similarities between OME and reactive arthritis, i.e . Lyme arthritis, Reiter's syndrome and rheumatic fever, are evident. Rhinology, 1992 Jun, 30(2), 103 - 12 Influence of topical steroid treatment on maxillary sinusitis; Qvarnberg Y et al.; The clinical efficacy and adverse effects of budesonide administered as a nasal aerosol in addition to sinus washings and erythromycin therapy was assessed by comparison with placebo in a randomized, double-blind study of 40 patients with chronic or recurrent maxillary sinusitis . Most of the patients had been referred for operative treatment . Corticosteroid therapy, 400 micrograms daily, or placebo was continued for 3 months . Budesonide and antral irrigations reduced nasal symptoms more effectively than placebo, and there was a significantly greater reduction in facial pain and sensitivity in the budesonide group than in the placebo group . During the treatment period, mucosal thickening as evaluated by radiology decreased more clearly in the budesonide group than in the placebo group, but the difference did not reach statistical significance . The most frequently isolated bacteria were Staphylococcus aureus, Staphylococcus epidermidis and Haemophilus influenzae . Only 2 of 20 Haemophilus strains were beta-lactamase producers . The cellular picture was dominated by neutrophils in all secretions . There was no significant difference in clinical outcome between the two groups . Topical steroid therapy did not cause any adverse effects. Enferm Infecc Microbiol Clin, 1992 Jun-Jul, 10(6), 355 - 9 {Resistance of Haemophilus influenzae and Haemophilus parainfluenzae to beta-lactam antibiotics . Characterization of the beta-lactamases}; Tirado M et al.; We have studied the susceptibility to ampicillin and the characteristics of the beta-lactamase activity of the 169 Haemophilus spp . strains (128 H . influenzae, 40 H . parainfluenzae and one H . paraphrophilus) isolated during 12 months, years 1988-1989, in the Hospital del Mar clinical microbiology laboratory . Our objective was to know in the strains of our center the frequency of those resistant or slightly susceptible to ampicillin, the role of beta-lactamases in the loss of susceptibility and the type of enzymes involved . Susceptibility was studied by diffusion for all the antibiotics tested and also confirmed by dilution for ampicillin and other beta-lactam antibiotics . Beta-lactamase production was identified by nitrocefin hydrolysis . The isoelectric point of the beta-lactamase and the identification of their types were determined by analytic isoelectric focusing . The presence of the codifying gene of the TEM-1 enzyme was studied by hybridization with a TEM-1 probe . Of the H . influenzae strains 35 were ampicillin resistant, one moderately susceptible and of the H . parainfluenzae strains six were resistant and two moderately susceptible; all were susceptible to the combination of amoxicillin/clavulanic acid . The ampicillin-resistant strains were beta-lactamase producers . In 40 strains, by isoelectric focusing, the type TEM-1 was identified and the hybridization was positive; in one H . parainfluenzae strain a beta-lactamase of pl 5.8 was observed and the hybridization with TEM-1 probe was negative . The three strains moderately susceptible to ampicillin did not produce beta-lactamase. J Bacteriol, 1992 Jun, 174(12), 4007 - 16 Antigenic sites on porin of Haemophilus influenzae type b: mapping with synthetic peptides and evaluation of structure predictions; Srikumar R et al.; The major surface-located protein in the outer membrane of Haemophilus influenzae type b (Hib) is porin, molecular mass, 38 kDa, 341 amino acids . To define precisely the molecular reactivities of nine mouse monoclonal antibodies (MAbs) against Hib porin, overlapping hexapeptides corresponding to the entire sequence of porin were synthesized . The epitopes recognized by the MAbs were mapped by enzyme-linked immunosorbent assay to stretches of 6 to 11 amino acids . Antigenic sites between amino acids 112 and 126, 148 and 153, 162 and 172, and 318 and 325 were identified . The antigenic sites between amino acids 162 and 172 and between amino acids 318 and 325 were determined by flow cytometry to be on the bacterial cell surface . Four MAbs, POR.2, POR.3, POR.4, and POR.5, that react with amino acids 162 to 172 were able to discriminate among porins from the three major outer membrane protein subtypes of Hib, i.e., 1H, 2L, and 6U . A model for the topological organization of Hib porin was created by calculating the hydrophobicity, amphiphilicity, and turn propensity in its amino acid sequence . Determination of the molecular reactivities of the anti-Hib porin MAbs provided substantive evidence for the orientation of selected regions of porin in the outer membrane of Hib. J Infect Dis, 1992 Jun, 165 Suppl 1, S53 - 6 Characterization of the human IgG antibody VL repertoire to Haemophilus influenzae type b polysaccharide; Scott MG et al.; The human antibody response to the capsular polysaccharide of Haemophilus influenzae type b (Hib) is a good model for examining human V region repertoires . While the VL repertoire of human antibodies to Hib polysaccharide is relatively simple and dominated by the product of a germline V kappa II gene named A2, at least five other VL genes can be expressed by some individuals . These include at least two V kappa I products and at least one V kappa III, one V kappa IV, and one V lambda product . The epitope recognized by a monoclonal anti-idiotype antibody is on the A2 V kappa II product. J Infect Dis, 1992 Jun, 165 Suppl 1, S188 - 91 Recombinant porin of Haemophilus influenzae type b; Coulton JW et al.; A protein of approximately 40 kDa in the outer membrane of Haemophilus influenzae type b (Hib) behaves as a porin and permits transmembrane diffusion of low-molecular-weight solutes . The gene for Hib porin was cloned from an M13 library of chromosomal DNA of Hib strain ATCC9795 . The gene was subcloned into a new transfer vector as a prerequisite for its use in the baculovirus expression vector system . Pure recombinant virus (AcPORIN) was isolated . On infection of a cultivated insect cell line Sf9 with AcPORIN, a novel protein was detected in cell lysates, and this novel protein reacted with an anti-Hib porin monoclonal antibody . The purified recombinant Hib porin was tested for its pore-forming properties in a synthetic black lipid membrane . The biophysical activity of purified recombinant Hib porin was identical to porin isolated from the bacterial outer membrane. J Infect Dis, 1992 Jun, 165 Suppl 1, S97 - 9 Fimbria-mediated adherence and hemagglutination of Haemophilus influenzae; van Ham SM et al.; The gram-negative bacterium Haemophilus influenzae expresses morphologically and functionally distinct types of fimbriae, of which the LKP fimbriae mediate hemagglutination and adherence to human epithelial cells but hamper mucosal invasion . Therefore, the both in vivo and in vitro observed fimbrial phase variation may contribute to the pathogenesis of the infection . The existence of greater than 14 LKP serotypes hampers vaccine development based on fimbriae, since a monovalent fimbria vaccine confers protection against only the homologous strain . Cloning of the fimbrial genes in Escherichia coli results in the expression of morphologically intact fimbriae . Analysis of the cloned DNA indicates that a fimbrial gene cluster is necessary for formation of complete fimbriae and for fimbria-mediated adherence . The gene encoding the subunit is highly conserved among H . influenzae and belongs to the family of E . coli fimbriae . The phase variation is transcriptionally regulated by variation of the length of the reiterated sequence that forms the promoter region of the subunit gene. Infect Immun, 1992 Jun, 60(6), 2257 - 66 The hbpA gene of Haemophilus influenzae type b encodes a heme-binding lipoprotein conserved among heme-dependent Haemophilus species; Hanson MS et al.; A membrane-associated lipoprotein of Haemophilus influenzae type b has previously been shown to bind heme in vitro and to promote binding of this compound by Escherichia coli recombinants expressing this protein . The H . influenzae type b heme-binding protein A (HbpA) was found to be highly conserved with respect to both antigenicity and apparent molecular weight among heme-requiring Haemophilus species pathogenic for humans . To further the characterization of the structure and function of HbpA, the complete nucleotide sequence of its gene, hbpA, was determined . Analysis of the nucleotide sequence revealed a single large open reading frame of 1,638 bp encoding a protein of 546 amino acid residues, with a molecular weight of 60,695 . The sequence of the amino-terminal end of this protein contained a potential site for lipid acylation and for cleavage by signal peptidase II, consistent with earlier biochemical evidence which indicated that HbpA is a lipoprotein . A search of GenBank for proteins with amino acid sequence similarity to HbpA revealed that the periplasmic dipeptide transport protein of E . coli, DppA, has 53% sequence identity to HbpA. Antimicrob Agents Chemother, 1992 Jun, 36(6), 1302 - 9 In vitro and in vivo intraleukocytic accumulation of azithromycin (CP-62, 993) and its influence on ex vivo leukocyte chemiluminescence; Bonnet M et al.; The accumulation of azithromycin in phagocytic cells was studied both in vitro by using a radiolabelled drug and a bioassay and in vivo for 12 volunteers receiving 1.5 g (total dose) orally within 3 days . In vitro, neutrophils and unfractionated blood leukocytes accumulated azithromycin up to 160-fold the extracellular concentration within 1 h at 37 degrees C but less than 3-fold at 4 degrees C . Dead cells accumulated up to 30-fold azithromycin, whereas NaF-treated cells accumulated up to 60-fold arithromycin . The mean efflux from preloaded cells was at most 31.0% +/- 10.6% (standard error of the mean) of the cell-associated concentration within 4 h of incubation at 37 degrees C in drug-free buffer . In vivo, the azithromycin concentration was 45.2 +/- 6.1 mg/liter of intracellular fluid at 2 h after the third dose and 36.6 +/- 8.3 mg/liter at 1 week thereafter . The corresponding concentrations in serum were 0.2 +/- 0.1 (2 h) and less than 0.05 (1 week) . The luminol-enhanced chemiluminescence response induced by phorbol myristate acetate, opsonized zymosan, and two opsonized strains of Haemophilus influenzae (a type b capsulated strain and a noncapsulated strain) was also studied ex vivo by using the blood leukocytes from the 12 test volunteers and 4 control volunteers at 2 and 6 h after the third oral dose of azithromycin and at 2, 4, and 7 days thereafter . Azithromycin did not influence this response despite high levels of cellular accumulation. Antimicrob Agents Chemother, 1992 Jun, 36(6), 1241 - 3 In vitro activity of azithromycin compared with that of erythromycin against Actinobacillus actinomycetemcomitans; Pajukanta R et al.; The in vitro susceptibility of Actinobacillus actinomycetemcomitans to azithromycin, a new macrolide antibiotic of a new class known as azalides, was compared with that of erythromycin by the agar dilution method on Mueller-Hinton Haemophilus test medium . Eighty-two A . actinomycetemcomitans strains, 79 recent clinical isolates obtained from 40 periodontally healthy or diseased subjects, and 3 type strains were included in the study . Erythromycin showed poor in vitro activity against A . actinomycetemcomitans . Azithromycin, however, was highly effective against A . actinomycetemcomitans: all strains were inhibited at 2.0 micrograms/ml . Azithromycin exhibited the best in vitro activity against the serotype a subpopulation of A . actinomycetemcomitans: 100% of the strains were inhibited at 1.0 micrograms/ml . The lowest MICs were, however, recorded by serotype b strains . Since azithromycin has favorable pharmacokinetic properties, including excellent distribution into tissues, it could be expected to pass into gingival crevicular fluid at levels sufficient to inhibit A . actinomycetemcomitans in vivo . Therefore, it is a good candidate for future clinical trials in A . actinomycetemcomitans-associated periodontitis. J Infect Dis, 1992 Jun, 165 Suppl 1, S93 - 6 The genetics of encapsulation in Haemophilus influenzae; Kroll JS; In Haemophilus influenzae type b (Hib) strains the cap locus with very few exceptions contains an unstable direct repeat of approximately 17 kb of DNA flanking an approximately 1-kb bridge region containing the gene bexA . Each repeat contains genes necessary for polysaccharide synthesis, export, and surface expression, with BexA a critical component of the polysaccharide exporter . Only rare Hib strains have been identified in which cap lacks a direct repeat, though this is the norm for non-b serotypes . Examination of the ends of this single-copy locus shows that cap has the structure of a compound transposon: Copies of the insertion element IS1016 flank the gene cluster . This gives strains the capacity to amplify genes at cap by unequal homologous recombination . The cap duplication in Hib strains--subserving augmented production of polysaccharide--has apparently arisen in this way and become fixed in the population through deletion of one copy of bexA. MMWR CDC Surveill Summ, 1992 May 29, 41(3), 57 - 61 Chancroid in the United States, 1981-1990: evidence for underreporting of cases; Schulte JM et al.; Chancroid, a bacterial sexually transmitted disease (STD) characterized by genital ulceration, has reemerged in the United States during the last decade . From 1950 to 1980, cases were infrequently reported . After an epidemic in California in 1981, however, the numbers of cases increased, peaking in 1987 at 5,035 . Despite a subsequent decline in numbers of reported cases to 4,223 in 1990, new areas continue to report outbreaks . Interpreting chancroid surveillance data is difficult because confirmatory culture media are not commercially available . In addition, states may not require that unconfirmed or even confirmed cases be reported . To determine if chancroid is more widely distributed than surveillance figures indicate, CDC contacted STD clinics in 115 health departments, located in 32 states, the District of Columbia, and Puerto Rico--areas chosen because they had reported five or more cases of chancroid in any single year during 1986-1990--to determine if cases might be occurring but not reported . Only 16 of the 115 clinics had culture media available for Haemophilus ducreyi, and only nine had laboratory facilities complete enough to definitively diagnose chancroid, syphilis, or genital herpes, the most common STDs characterized by genital ulcers . Five or more clinically likely cases occurring in 1990 were identified in 24 states, seven more than surveillance figures indicated . Surveillance can be improved if a) states utilize the definitions for chancroid cases adopted for use in 1990 and b) microbiology laboratories utilize enhanced diagnostic methods. Ann Intern Med, 1992 May 15, 116(10), 806 - 12 Invasive Haemophilus influenzae disease in adults . A prospective, population-based surveillance . CDC Meningitis Surveillance Group; Farley MM et al.; OBJECTIVE: To define the incidence of and possible risk factors for invasive Haemophilus influenzae disease in adults . DESIGN: Prospective, population-based surveillance of hospital and referral bacteriology laboratories . SETTING: Metropolitan Atlanta, Georgia community . PATIENTS: All patients with H . influenzae isolated from normally sterile sites (blood, cerebrospinal fluid, joint, pleura) from 1 December 1988 through 31 May 1990 . MEASUREMENTS: Isolates of H . influenzae were analyzed for serotype and biotype status, outer membrane proteins, lipooligosaccharide phenotypes, ribotyping patterns and beta-lactamase production . RESULTS: A total of 194 cases of invasive H . influenzae occurred (annual incidence of 5.6 cases/100,000 population), of which 47 (24%) were in adults 18 years old or older (annual incidence 1.7 cases/100,000 adults) . Adults with invasive H . influenzae ranged from 18 to 96 years; 79% were women . Bacteremic pneumonia accounted for 70% of the adult cases . Other sources for invasive H . influenzae in adults were obstetric infections, epiglottitis, and tracheobronchitis; one patient had meningitis . Underlying conditions were noted in 92% of the patients . Chronic lung disease was the most common risk factor, but pregnancy (annual incidence, 4.9/100,000 pregnant women), HIV infection (annual incidence, 41/100,000 known HIV-infected adults), and malignancy were also important . Overall mortality was 28% in adults, and over half of pregnancy-related infections resulted in fetal death . Fifty percent of the 40 isolates available for testing were serotype b; 47.5%, nontypable; and 2.5%, serotype f . Sixteen of the 45 isolates (36%) were ampicillin-resistant . Based on biotypes, outer membrane protein profiles, lipooligosaccharide phenotypes, and ribotyping patterns, the type b isolates showed less heterogeneity than the nontypable isolates but were distinguishable from one another . CONCLUSIONS: Adult cases currently represent one quarter of all cases of invasive H . influenzae disease . Half of the reported adult cases were caused by type b H . influenzae, and the rate of ampicillin resistance in H . influenzae isolates from adults was higher than previously reported . Haemophilus influenzae is an important cause of bacteremia in compromised adults. S Afr Med J, 1992 May 16, 81(10), 495 - 8 The clinical significance of Haemophilus influenzae and H . parainfluenzae isolated from the sputum of adult patients at an urban general hospital; Feldman C et al.; Fifty-seven patients, from whose sputum Haemophilus influenzae (49 cases) or Haemophilus parainfluenzae (8 cases) was isolated during a 7-month period, were studied . In the majority of cases there were well-defined predisposing factors to respiratory tract colonisation or infection with the isolates, in particular bronchiectasis and chronic obstructive airways disease . Colonisation of the airways, bronchopneumonia in patients with underlying lung disease, acute lobar pneumonia, and postoperative chest infections were the commonest clinical diagnoses . Primary acute lobar pneumonia with these organisms alone was uncommon . All of the H . influenzae isolates were nontypeable, and there was a wide range of biotypes of both organisms . Three H . influenzae isolates produced beta-lactamase, and there was, in general, a low incidence of resistance to a wide range of antimicrobial agents on disc susceptibility testing. FEMS Microbiol Lett, 1992 May 15, 72(1), 43 - 7 Growth of Haemophilus influenzae type b in continuous culture: effect of dilution rate on outer-membrane protein and lipopolysaccharide expression; Langford PR et al.; Haemophilus influenzae type b (Hib) was grown in continuous culture under cystine-limitation between dilution rates (D) of 0.065-0.28 h-1 . A similar outer-membrane protein profile, as adjudged by SDS-PAGE, was found at all dilution rates . However, a shift to a lipopolysaccharide structure with a greater electrophoretic mobility on SDS-PAGE with accompanying changes in monoclonal antibody reactivity was observed at D greater than or equal to 0.15 h-1 . Growth rate per se can affect the expression of outer-membrane components of Hib. Proc Natl Acad Sci U S A, 1992 May 15, 89(10), 4633 - 7 A vaccine carrier derived from Neisseria meningitidis with mitogenic activity for lymphocytes; Liu MA et al.; Protein carriers vary in their ability to increase the immunogenicity of poorly immunogenic or T-lymphocyte-independent antigens . We examined one such carrier, the outer membrane protein complex derived from Neisseria meningitidis serogroup B strain B11, in an attempt to determine why this outer membrane protein complex was more immunogenic in young infants and in relevant animal models than two other carriers used in conjugates made with Haemophilus influenzae type b polysaccharide, a T-cell-independent antigen . A single protein of the outer membrane protein complex, the class 2 porin protein, was purified and shown to function as a T-helper lymphocyte carrier protein . Unexpectedly, it was also found to have mitogenic activity for lymphocytes that was not due to lipopolysaccharide . This mitogenic activity appears to date to be unique to this carrier protein of the carrier proteins tested and may contribute to the ability of the H . influenzae type b conjugate vaccine made with the outer membrane protein complex to generate IgG anti-polysaccharide antibody responses in mice and infant monkeys and protective immune responses in infants less than 6 months of age. Biochemistry, 1992 May 12, 31(18), 4515 - 26 Structural characterization of the cell surface lipooligosaccharides from a nontypable strain of Haemophilus influenzae; Phillips NJ et al.; Oligosaccharides released from the lipooligosaccharides (LOS) of Haemophilus influenzae nontypable strain 2019 by mild acid hydrolysis were fractionated by size exclusion chromatography and analyzed by liquid secondary ion mass spectrometry . The major component of the heterogeneous mixture was found to be a hexasaccharide of Mr 1366, which lost two phosphoethanolamine groups upon treatment with 48% aqueous HF . The dephosphorylated hexasaccharide was purified and shown by tandem mass spectrometry, composition analysis, methylation analysis, and two-dimensional nuclear magnetic resonance studies to be Gal beta 1----4Glc beta 1----(Hep alpha 1----2Hep alpha 1----3) 4Hep alpha 1----5anhydro-KDO, where Hep is L-glycero-D-manno-heptose and KDO is 3-deoxy-D-manno-octulosonic acid . An analogous structure containing authentic KDO was generated from LOS that had been HF-treated prior to acetic acid hydrolysis, suggesting that the reducing terminal anhydro-KDO moiety is produced as an artifact of the hydrolysis procedure by beta-elimination of a phosphate substituent from C-4 of KDO . Mass spectral analyses of O-deacylated LOS and free lipid A confirmed that, in addition to the two phosphoethanolamines on the oligosaccharide and two phosphates on the lipid A, another phosphate group exists on the KDO . This KDO does not appear to be further substituted with additional KDO residues in intact H . influenzae 2019 LOS . The terminal disaccharide epitope, Gal beta 1----4Glc beta 1----, of the hexasaccharide is also present on lactosylceramide, a precursor to human blood group antigens . It is postulated that the presence of this structure on H . influenzae LOS may represent a form of host mimicry by the pathogen. J Chromatogr, 1992 May 8, 576(2), 328 - 33 Intra-injector methylation of free fatty acids from aerobically and anaerobically cultured Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus; Brondz I et al.; Free fatty acids from the type strains of anaerobically and aerobically broth-cultured Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus cells were Soxhlet-extracted with hexane . The fatty acids were identified and quantified by gas chromatography and gas chromatography-mass spectrometry after intra-injector derivation with trimethylanilinium hydroxide . This derivatization method, which we propose as suitable for routine use in clinical microbiology, is fast, accurate and sensitive, with low toxicity . Whereas the fatty acid content of A . actinomycetemcomitans was affected by the cultivation atmosphere, i.e . C16:1, decreased under aerobic growth and C16:0 increased, that of the closely related H . aphrophilus was more stable. Br J Hosp Med, 1992 May 6-19, 47(9), 684 - 7 Antibiotic resistance in community-acquired pneumonia; Woodhead M; Antibiotic resistance in bacteria is but one of many factors to consider when treating patients with community-acquired pneumonia . Many bacterial resistance patterns are stable, but wide geographical variation, increasing penicillin resistance in pneumococci and ampicillin resistance in Haemophilus influenzae are now being found . The importance of these features and their impact on therapy are reviewed. Pediatr Infect Dis J, 1992 May, 11(5), 374 - 9 Efficacy of Haemophilus influenzae type b vaccines in Massachusetts children 18 to 59 months of age; Loughlin AM et al.; Since 1987 Haemophilus influenzae b (Hib) conjugate vaccines have been licensed for use in children ages 18 months and older . Before licensure there were no clinical trials of a single dose of any conjugate vaccine in children ages 18 months or older . To fulfill this need we performed an age- and residence-matched case-control study of the efficacy of Hib vaccines . In our study population the protective efficacy (PE) of Hib-diphtheria toxoid conjugate vaccine was 88% (95% confidence interval, 45 to 98%) . No vaccine failures were observed with Hib oligosaccharide CRM197 diphtheria protein conjugate vaccine, but usage was not sufficient to establish efficacy: PE = 100% (95% confidence interval, -37 to 100%) . The protective efficacy of Hib capsular polysaccharide vaccine was 18% (95% confidence interval -487 to 89%) . We conclude that for children ages 18 to 60 months a single dose of the Hib conjugate vaccine, PRP-D, is protective against invasive Hib infections . Consistent with most studies Hib polysaccharide vaccine provided suboptimal protection. J Antimicrob Chemother, 1992 May, 29(5), 547 - 54 Antimicrobial resistance in Haemophilus influenzae from England and Scotland in 1991; Powell M et al.; Twenty-two laboratories in England and Scotland sent 2212 clinical isolates of Haemophilus influenzae to The London Hospital Medical College (LHMC) between 1 January and 31 March 1991 . After confirmation of identity, the prevalence of resistance was determined and compared with results from previous similar surveys . beta-Lactamase was produced by 8.3% of non-capsulate isolates and 21% of 52 type b isolates; both figures were higher than the 6% and 18% figures recorded, respectively, in 1986 . There was an increase in the prevalence of non-beta-lactamase-mediated diminished susceptibility to ampicillin (5.8%) and co-amoxiclav (6.1%) compared with 1986 (4%) . Whereas fewer H . influenzae isolates were resistant to tetracycline (1.4%) or chloramphenicol (0.8%), there was an increase in resistance to trimethoprim (6.8%) and to sulphamethoxazole (16.9%) compared with 1986 (4.2% and 3.5% respectively) . In addition, 95 isolates (4.3%) were resistant to both of these anti-folate antimicrobials . Six isolates (one type b from CSF) were resistant to all drugs tested, except for co-amoxiclav . Overall, the results demonstrated that changes have occurred in the last decade in England and Scotland, such that H . influenzae isolates are increasingly likely to be resistant to ampicillin, co-amoxiclav and co-trimoxazole. Pediatr Neurol, 1992 May-Jun, 8(3), 210 - 4 Aerobic and anaerobic bacteriology of intracranial abscesses; Brook I; The bacteriologic and clinical findings of 39 pediatric patients with intracranial abscess are presented . Twenty-three children presented with brain abscess and 16 with subdural empyema . Predisposing conditions were present in all instances . Sinusitis was present in 25 children and 4 patients each had chronic otitis media, dental abscess, and congenital heart disease . The abscess was located in the frontal area in 14 patients, parietal in 13, and temporal in 12 . Anaerobic organisms alone were recovered in 22 patients (56%), aerobic bacteria alone in 7 (18%), and mixed aerobic and anaerobic bacteria in 10 (26%) patients . There were 79 anaerobic isolates (2 per specimen) . The predominant anaerobes were anaerobic Gram-positive cocci (29 isolates); Bacteroides sp . (12, including 5 Bacteroides fragilis group), Fusobacterium sp . (14 isolates); and Prevotella sp . and Actinomyces sp . (6 isolates each) . A total of 17 aerobic or facultative isolates (0.4 per specimen), including 11 Gram-positive cocci and 6 Haemophilus sp., were recovered . Antimicrobial therapy was administered to all patients . Nine patients (i.e., 6 with sinusitis and subdural empyema, 3 with sinusitis and brain abscess) did not respond to antimicrobial therapy and aspiration of the abscess, and required surgical drainage of inflamed sinuses . These findings indicate the major role of anaerobic organisms in the polymicrobial etiology of intracranial abscess in children.
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