Am J Dis Child, 1992 May, 146(5), 560 - 6 Severity and frequency of sequelae of bacterial meningitis in Alaska Native infants . Correlation with a scoring system for severity of sequelae; Letson GW et al.; OBJECTIVES--To (1) determine the frequency and severity of sequelae of Haemophilus influenzae type b and Streptococcus pneumoniae meningitis in Alaska Native children, (2) compare morbidity and mortality of H influenzae b and S pneumoniae meningitis, and (3) evaluate the applicability of the Herson-Todd prognostic score (HTPS) to both H influenzae b and S pneumoniae meningitis in this population . DESIGN--A retrospective study of all cases of H influenzae b and S pneumoniae meningitis in Alaska Native children younger than age 5 years . Data on meningitis sequelae, obtained from medical charts and records of the Infant Learning Program, were collected, and incidence of sequelae tabulated . Data obtained on admission to the hospital were used to calculate HTPS . SETTING--Indian Health Service facility for the Yukon-Kuskokwin Delta region of southwest Alaska . STUDY SUBJECTS--51 of 63 Alaska Native children with H influenzae b meningitis and 13 of the same 63 Alaska Native children with S pneumoniae meningitis occurring between 1980 and 1988 . One child was infected with both organisms, producing a total of 64 cases for study . SELECTION PROCEDURES--Cases were identified by surveillance for these diseases between January 1, 1980, and December 31, 1988, maintained by the Arctic Investigations Program, Centers for Disease Control . MEASUREMENTS AND RESULTS--Sequelae of bacterial meningitis caused by H influenzae b were equal to or exceeded rates of sequelae described in other children in the United States . After H influenzae b meningitis, motor abnormalities (29%) and hydrocephalus (7%) occurred two to four times more often in Alaska Native children than in children in other parts of the United States . Differences in severity of H influenzae b sequelae could not be accounted for by microbiologic markers of the H influenzae b strain, including ampicillin sensitivity, biotype, outer membrane protein type, or electropherotype . Numbers of cases of S pneumoniae meningitis were too small for statistically valid comparison, but sequelae of S pneumoniae meningitis occurred in roughly equal proportion as sequelae of H influenzae b meningitis . The HTPS was applied to Alaska Native children with H influenzae b meningitis and was found to be very accurate in predicting children with major sequelae . Analysis of the prognostic factors used in deriving the HTPS revealed a unique set of predictors for sequelae in Alaska Native children: seizures at admission, glucose levels in cerebrospinal fluid of less than 1.1 mmol/L; and male gender, with a significant predictive interaction between male gender and age less than 6 months at admission . CONCLUSIONS--Alaska Native children suffer greater neurologic morbidity as a result of H influenzae b meningitis than do their non-Native counterparts . The HTPS was a good predictor of major sequelae in Alaska Native children with H influenzae b or S pneumoniae meningitis and could be useful in determining which patients need referral to a tertiary care center. Diagn Microbiol Infect Dis, 1992 May-Jun, 15(4 Suppl), 97S - 101S A randomized double-blind controlled trial of roxithromycin and cefaclor in the treatment of acute lower respiratory tract infections in general practice; Tilyard MW et al.; A multicenter, randomized, double-blind, single-dummy placebo-controlled study is being undertaken by the Research Unit of the Royal New Zealand College of General Practitioners to compare the efficacy and tolerance of 150 mg twice daily roxithromycin with 250 mg three times daily cefaclor in the treatment of 250 general practice patients with acute lower respiratory tract infections (LRTIs) . Interim analysis of 200 patients reveals no statistically significant differences in the study parameters . Of the patients on roxithromycin and cefaclor, 83% and 67%, respectively, had a moderate or severe illness . Based on efficacy criteria, 96% of roxithromycin recipients and 99% of cefaclor recipients had a satisfactory or improved response . On an intention-to-treat basis, this was reduced to 95% for both treatment groups . Sputum grading and semiquantitative culturing was performed according to NCCLS standards . The most common isolates in order were Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae . Efficacy for bacteriologically evaluable cases was 87.5% for roxithromycin and 57% for cefaclor . Four patients on roxithromycin (3.9%) and 11 patients on cefaclor (11.3%) withdrew because of side effects probably or possibly related to the study treatment . The study is ongoing. AIDS, 1992 May, 6(5), 489 - 93 Association between HIV-2 infection and genital ulcer diseases among male sexually transmitted disease patients in The Gambia; Pepin J et al.; OBJECTIVE: To investigate whether genital ulcer diseases are cofactors which enhance the transmission of HIV-2 in West Africa . DESIGN: A cross-sectional study of 435 men presenting with a sexually transmitted disease (STD) . SETTING: The outpatient clinic of the Medical Research Council Laboratories, a primary care facility in Fajara, a suburb of Banjul, the capital city of The Gambia (West Africa) . PATIENTS, PARTICIPANTS: Six hundred and twenty-four men presenting with a genital complaint, of whom 443 had an STD . Eight of the men with an STD were excluded from further analysis because they were HIV-1-infected (five patients) or had indeterminate Western blot patterns (three patients) . The remaining 21 HIV-2-infected and 414 seronegative men constituted our study-group . MAIN OUTCOME MEASURES: Participants were questioned about previous STD and behavioural and demographic characteristics . A physical examination was performed and serum collected for measurement of antibodies against Haemophilus ducreyi and Treponema pallidum . RESULTS: HIV-2-infected men were more likely than HIV-seronegative participants to have previously had a genital ulcer {odds ratio (OR), 3.00; 95% confidence interval (Cl), 1.18-7.60} and to have antibodies against T . pallidum (OR, 5.95; 95% Cl, 2.10-16.91), or H . ducreyi (OR, 4.59; 95% Cl, 1.71-12.33) . Circumcised patients with residual foreskin were more likely to be HIV-2 infected than patients with complete circumcision . HIV-2-seropositive patients were six times more likely to have generalized lymphadenopathy than their seronegative counterparts . CONCLUSIONS: Our data suggest that genital ulcerative diseases, such as syphilis and chancroid, are probably cofactors that increase the transmission of HIV-2 in West Africa, and that HIV-2 infection frequently results in generalized lymphadenopathy. Salud Publica Mex, 1992 May-Jun, 34(3), 274 - 86 {Vaccines against Haemophilus influenzae B: present, past and future}; Gomez de Leon-Cruces P et al.; Haemophilus influenzae type b (Hinb) is the main etiologic agent of severe pediatric illnesses, such as meningitis, epiglottitis and pneumonia . Countries most affected by this pathogen are localized in the American, European and African continents . While this organism was originally isolated 100 years ago, the first field trial using a whole killed vaccine was performed until 1959 . Since then, further controlled clinical trials have mainly been conducted in the North American and European continents . Under appropriate safety and efficacy evaluation tests performed by the Federal Drug Administration Agency (FDA), five vaccines were licensed: one single and four conjugated preparations . Worldwide and regional epidemiologic data concerning serious diseases produced by this organism have shown their outstanding impact in the public health of developed countries . Unfortunately, in developing countries similar epidemiological indexes are lacking for lethal and disabling diseases, such as meningitis . In order to decrease high morbidity and mortality rates of this meningeal disease and its neurological sequelae, immunoprophylactic preventive measures have been recommended . Furthermore, some risk factors of this infant illness can also be reduced . New strategies regarding conjugate Hib-vaccines are reviewed . Finally, promising virulence factors or self Hib-structures for the production of vaccines are suggested, such as outer membrane proteins (OMP), lipooligosaccharides, fimbriae or pili. J Infect, 1992 May, 24(3), 317 - 20 Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin; Dawson SJ et al.; A patient with Haemophilus aphrophilus endocarditis was successfully treated with ciprofloxacin . The response to treatment with cefotaxime and netilmicin for 12 days was poor but was satisfactory to a 6 weeks' course of ciprofloxacin. Clin Infect Dis, 1992 May, 14(5), 1119 - 23 Update on mechanisms and prevalence of antimicrobial resistance in Haemophilus influenzae; Jorgensen JH; The prevalence of plasmid-mediated beta-lactamase production among clinical isolates of Haemophilus influenzae has increased globally since this characteristic was first recognized in 1972 . Three nationwide surveillance studies conducted in the United States in the 1980s indicated that the rate of beta-lactamase production was approximately 30% among serotype b isolates and approximately 15% among nonencapsulated strains . The American studies also documented strains with resistance to chloramphenicol, tetracycline, trimethoprim-sulfamethoxazole, rifampin, erythromycin, and certain older cephalosporins . Surveillance studies performed at about the same time in Canada, Europe, the United Kingdom, and several developing countries have also documented the prevalence of beta-lactamase-producing isolates and resistance among them to alternative agents such as chloramphenicol and tetracycline . Perhaps of greatest concern has been the isolation of H . influenzae (both serotype b and nonencapsulated strains) in the United States, Europe, and Asia that possess multiple antimicrobial resistance mechanisms . At the present time, H . influenzae isolates have not been detected that are resistant to either third-generation cephalosporins or fluoroquinolones. Arch Dis Child, 1992 May, 67(5), 592 - 4 Role of infection in the middle lobe syndrome in asthma; Springer C et al.; Twenty one children with asthma aged 1.0-10.5 years (mean (SD) 3.3 (2.5) years) were admitted to the hospital to evaluate pulmonary right middle lobe or lingular collapse lasting one to 12 months (mean (SD) 4.4 (3.8) months) . Seven children had mild asthma and were treated with inhaled beta 2 agonists as needed . Nine had moderate asthma treated with either sodium cromoglycate or slow release theophylline . Five had severe asthma treated with inhaled steroids . Each child underwent fibreoptic bronchoscopy under local anaesthesia and a bronchoalveolar lavage . Differential cell counts of the lavage fluid revealed predominance of neutrophils in 12 patients (57%) . In nine of these patients cultures grew pathogenic bacteria, mainly Haemophilus influenzae and Streptococcus pneumoniae . There was no correlation between the severity of asthma and a positive bacterial culture . There was also no correlation between the duration of the right middle lobe collapse and a positive culture . We conclude that longstanding right middle lobe collapse in asthmatic children is often associated with bacterial infection. Public Health Rep, 1992 May-Jun, 107(3), 252 - 6 Six areas lead national early immunization drive; Woods DR et al.; On June 13, 1991, President George Bush announced in a White House ceremony a local planning effort to break down barriers and provide better access to immunization in six representative localities "to solve the problem of late immunization." (children need to be immunized appropriately by their second birthday, not just in time for school.) . The community "Immunization Action Plans" (IAP) are one of several Federal, State, and local responses to an outbreak of measles that produced 27,600 cases and 89 deaths in 1990 . The community effort and subsequent early childhood immunization plans around the country are also part of a much broader effort initiated by Secretary Sullivan as a Healthy People Year 2000 goal to increase immunization levels to at least 90 percent for the nation's children by their second birthday . These efforts also respond to 13 recommendations for improving immunization availability made by the National Vaccine Advisory Committee in January 1991 . The recommendations focused on improvements in the management of immunization delivery and in methods for measuring immunization status, increasing appropriate consumer demand, and other prevention needs . Although measles prompted the action, the immunization initiative is aimed also at eight other communicable childhood diseases--diphtheria, tetanus, pertussis or whooping cough, poliomyelitis, mumps, rubella, and Haemophilus influenza type b that causes bacterial meningitis, and hepatitis B . Details are described of the immunization action plans developed by Dallas, TX; Maricopa County (Phoenix), AZ; South Dakota; Detroit, MI; San Diego, CA; and Philadelphia, PA, to ensure that children are fully immunized not just by the time they enter school but by age 2 years.(ABSTRACT TRUNCATED AT 250 WORDS) J Med Microbiol, 1992 May, 36(5), 358 - 65 Production and characterisation of mouse monoclonal antibodies reactive with the lipopolysaccharide core of Pseudomonas aeruginosa; Nelson JW et al.; Monoclonal antibodies (MAbs) to the core antigen region of lipopolysaccharide (LPS) of Pseudomonas aeruginosa were produced from mice immunised with whole cells of heat-killed rough mutants of Pseudomonas aeruginosa expressing partial or complete core LPS . MAbs were screened in an enzyme-linked immunosorbent assay (ELISA) against three different antigen cocktails: S-form LPS from three P . aeruginosa strains, R-form LPS from six P . aeruginosa strains and, as a negative control, R-form LPS from Salmonella typhimurium and Escherichia coli . Selected MAbs were subsequently screened against a range of extracted LPS and whole cells from both reference strains and clinical isolates of P . aeruginosa . The antibodies were also screened in ELISA against whole-cell antigens from other Pseudomonas spp . as well as strains of Haemophilus influenzae, Neisseria subflava and Staphylococcus aureus . Five MAbs reacting with the core component of P . aeruginosa LPS were finally selected . Two of these, MAbs 360.7 and 304.1.4, were particularly reactive in immunoblots against unsubstituted core LPS, including that from O-antigenic serotypes of P . aeruginosa . The MAbs also reacted with some of the other Pseudomonas spp., but not with P . cepacia or Xanthomonas (Pseudomonas) maltophilia . Cross-reactivity with whole cells from other bacterial species was minimal or not observed . Reactivity of MAbs with some Staph . aureus strains was observed, and binding to the protein A component was implicated . The reactivity of the MAbs was investigated further by flow cytometry and immunogold electronmicroscopy . The suitability of the MAbs for an immunological assay for detection of P . aeruginosa in respiratory secretions from CF patients is discussed. J Med Microbiol, 1992 May, 36(5), 312 - 7 Experimental rabbit model of meningitis produced by Haemophilus influenzae serotype c; Sulc P et al.; The virulence of Haemophilus influenzae type c when inoculated intracisternally (i.c.) into rabbits was evaluated . Rabbits are relatively resistant to infection with H . influenzae type b, such that inocula of the order of 10(6-9) cfu are required to produce meningitis in this model . In contrast, fatal meningitis was produced in this study when 10(3) cfu of a type-c strain were injected i.c . into rabbits . Numbers of bacteria in cerebrospinal fluid (CSF) of control (untreated) animals generally increased to 10(7) cfu/ml . Increases in white blood cells, protein and lactate in the CSF were similar to those which had been observed during meningitis due to Streptococcus pneumoniae in rabbits . The infection was amenable to therapy with ampicillin 50 mg/kg given intravenously 12 h after infection . Numbers of bacteria in CSF were reduced to 2.2 x 10(3) cfu/ml (SEM 0.2 x 10(3)) at 8 h after treatment with a single dose of ampicillin . Two doses of ampicillin, given 12 and 20 h after infection, significantly increased the mean survival time . In contrast to previous experimental studies with rabbits, the penetration of ampicillin into the CSF was high--46 (SEM 10) % of the blood level . Since considerable replication of H . influenzae type c occurred within the CSF in this model, the nature of the meningeal damage produced was likely to be similar to that which takes place in man . Hence, H . influenzae type c meningitis in rabbits may provide a useful model in which therapeutic and other experimental studies of H . influenzae meningitis can be performed. Gene, 1992 May 1, 114(1), 151 - 2 Palindromic Haemophilus DNA uptake sequences in presumed transcriptional terminators from H . influenzae and H . parainfluenzae; Kroll JS et al.; We have found palindromic pairs of near matches to the 11-bp Haemophilus DNA uptake motif shortly after the stop codons of three Haemophilus genes . Short runs of thymidylate residues follow the stem-loop structures thus defined . This organization suggests that, in H . influenzae, the uptake motif may be preferentially incorporated into gene termination signals, as has been proposed for Neisseria gonorrhoeae. J Clin Microbiol, 1992 May, 30(5), 1145 - 7 Performance of Haemophilus Test Media prepared with 12 different lots of Mueller-Hinton agar from four manufacturers; Barry AL et al.; Haemophilus Test Media (HTM) were prepared from 12 different lots of Mueller-Hinton agar . When tested with Haemophilus influenzae ATCC 49247, most lots were initially rejected because of small zones of inhibition for cefaclor, cefuroxime, and cefamandole disks, whereas five other drugs performed satisfactorily on the 11 lots that supported growth of the control strain . At the same time, tests of Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923 documented the acceptability of these agar media, with or without HTM supplements . The current control limits for cefaclor, cefuroxime, and cefamandole appear to be unrealistic . Because the beta-lactamase-negative, ampicillin-resistant control strain of H . influenzae (ATCC 49247) has altered penicillin-binding proteins, it is resistant to ampicillin and is probably also resistant to cefaclor, cefuroxime, and cefamandole . Consequently, media that produce no or very small zones of inhibition with those three drugs might be clinically correct and should not be rejected . One manufacturer provided three lots of Mueller-Hinton agar that gave unusually large zones of inhibition with all beta-lactams . The three other manufacturers provided eight Mueller-Hinton agars that were satisfactory for the preparation of HTM agar, provided that small zones of inhibition with cefaclor, cefuroxime, and cefamandole disks are accepted as the preferred result. J Bacteriol, 1992 May, 174(10), 3392 - 4 Donor DNA processing is blocked by a mutation in the com101A locus of Haemophilus influenzae; Larson TG et al.; Evidence is presented indicating that a donor DNA processing step of the Haemophilus influenzae transformation pathway is blocked in the Com-101 mutant . Additional data are presented suggesting that, as in the Rec-2 strain, the donor DNA remains associated with the H . influenzae envelope. Radiol Clin North Am, 1992 May, 30(3), 507 - 23 Immune function and dysfunction . A primer for the radiologist; Rubin JT et al.; Freedom from infection is the result of many tiers of immune defenses that harmoniously interact to rid the body of microorganisms and their products, which are perceived as foreign . The ability to distinguish self from nonself is embodied in lymphocytes, which serve both effector and regulatory functions . Through the elaboration of cytokines and immunoglobulins, lymphocytes recruit nonspecific immune effectors, focus their activity, and modulate the intensity of the immune response . The phylogenetically more primitive complement system serves a similar function . Although congenital defects in immune function occur, by far the most common causes of immunodeficiency are acquired and occur in patients treated for cancer with myelosuppressive, cytolytic drugs and in transplant recipients treated with immunosuppressants . HIV infection and malnutrition are responsible for even larger numbers of immunocompromised patients worldwide . The nature and severity of infections that occur as a result of immunodeficiency vary as a function of the immune effector targeted and the degree to which it is dysfunctional . Granulocytopenia is well tolerated unless the absolute number of circulating cells falls below 500/mm3 . Profound granulocytopenia and deficits of neutrophil function are often manifest as bacterial or fungal infections . Complement deficiency predisposes to infection with encapsulated bacteria such as pneumococci, meningococci, and Haemophilus influenzae . T cells play such a central role in the immune response that their derangement is associated with susceptibility to almost any potential pathogen . These patients often succumb to mortal opportunistic infections . Recent advances in hybridoma and recombinant DNA technology have provided us with immunologic reagents that enable us to manipulate the immune response . Anti-CD3 monoclonal antibody has permitted salvage of solid organ transplants in well-defined clinical settings . Monoclonal antibodies against TNF-alpha and lipopolysaccharide may alter the consequences of gram-negative sepsis . Alternatively, recombinant cytokines have been associated with clinically significant tumor regression in selected patients, presumably by enhancing the nascent antitumor immune response . The development of immunologic reagents such as these in concert with our growing understanding of the immune system may translate to improved care for immunocompromised patients. J Infect Dis, 1992 May, 165(5), 949 - 52 A randomized, double-blind study of the efficacy of fleroxacin versus trimethoprim-sulfamethoxazole in men with culture-proven chancroid; Plourde PJ et al.; Chancroid is linked to the spread of human immunodeficiency virus type 1 (HIV-1) in East Africa . Effective, easily administered therapy is a priority for the control of Haemophilus ducreyi . The efficacy of a single oral dose of fleroxacin, 400 mg, was compared to a 3-day oral course of trimethoprim-sulfamethoxazole (TMP-SMZ), 160/800 mg, twice daily for the treatment of chancroid in 98 HIV-1-seronegative men in Nairobi, Kenya . No differences were noted between the two groups with respect to demographic characteristics, sexual behavior, and clinical characteristics . Culture-proven failure occurred in 1 (3%) of 36 fleroxacin-treated patients and in 11 (30%) of 37 TMP-SMZ-treated patients (P = .005) . Fleroxacin, as a single oral dose, is an effective treatment for culture-proven chancroid in patients who are HIV-1 seronegative . TMP-SMZ is no longer predictably effective due to the recent emergence of resistance to both sulfonamides and to trimethoprim. J Infect Dis, 1992 May, 165(5), 942 - 4 C4B deficiency is not associated with meningitis or bacteremia with encapsulated bacteria; Cates KL et al.; The two isotypes of the fourth complement component are C4A and C4B . C4B forms ester bonds more efficiently than C4A and so, in theory, is more likely than C4A to bind to polysaccharide capsules of encapsulated bacteria . Two studies have reported homozygous C4B deficiency in patients with meningitis or bacteremia caused by encapsulated organisms . In the present study the association between C4B deficiency and these disorders was evaluated in four groups: patients with bacteremia, those with meningitis, those who developed Haemophilus influenzae type b (Hib) disease after Hib polysaccharide vaccination, and patients less than 1 year old with meningitis . Healthy adults served as controls . Of the 257 patients, 2.3% had homozygous C4B deficiency compared with 3.7% of 349 controls . According to these data, there is no increase in homozygous C4B deficiency among patients with bacteremia or meningitis caused by encapsulated bacteria. Infect Immun, 1992 May, 60(5), 1826 - 33 Synthetic trimer and tetramer of 3-beta-D-ribose-(1-1)-D-ribitol-5-phosphate conjugated to protein induce antibody responses to Haemophilus influenzae type b capsular polysaccharide in mice and monkeys; Peeters CC et al.; Synthetic oligosaccharides derived from the capsular polysaccharide (PRP) of Haemophilus influenzae type b were conjugated to carrier proteins via a thioether linkage . Conjugates were made of trimeric and tetrameric ribose-ribitol-phosphate and tetanus toxoid or diphtheria toxin . All conjugates elicited anti-PRP antibody responses with an increasing immunoglobulin G/immunoglobulin M ratio in adult mice and monkeys . Trimer conjugates elicited lower anti-PRP antibody responses compared with tetramer conjugates . Adult monkeys responded equally well to the tetrameric oligosaccharide-tetanus toxoid conjugate as to the oligosaccharide-CRM197 conjugate (HbOC), which elicits protective levels of serum antibodies in human infants after two or three injections. J Infect Dis, 1992 May, 165(5), 945 - 8 Effect of pertussis toxin on susceptibility of infant rats to Haemophilus influenzae type b; Samore MH et al.; Pertussis toxin is an important virulence factor of Bordetella pertussis that may also contribute to the toxicity of pertussis vaccines . The effect of low doses of pertussis toxin on response to Haemophilus influenzae type b (Hib) infection was examined in infant rats . Pretreatment of rats with 10 or 100 ng of pertussis toxin increased blood bacterial concentration (P less than .01), serum endotoxin levels (P less than .01), and mortality (P less than .05) relative to saline pretreated controls challenged with 4 x 10(3) Hib intraperitoneally . The 100-ng dose of pertussis toxin, but not the 10-ng dose, increased the leukocyte count . Thus, doses of pertussis toxin less than the threshold dose for inducing leukocytosis may enhance the susceptibility of infant rats to Hib infections. Am J Vet Res, 1992 May, 53(5), 659 - 64 Prevalence of Haemophilus parasuis serovars among isolates from swine; Rapp-Gabrielson VJ et al.; Two hundred sixty Haemophilus spp isolates that had been obtained from the respiratory tract and other sites of swine were acquired from diagnostic laboratories, primarily in the United States and Canada . The majority of isolates (243/260) were biochemically characterized as H parasuis; however, a few isolates of taxa distinct from H parasuis (taxa "minor group," D, E, and F) were identified . Fourteen H parasuis serovars were identified, and of those previously described, the most prevalent were 5 (24.3% of isolates), 4 (16.1%), 2 (8.2%), and 7 (3.7%) . Three new serovars that were also prevalent included ND4 (11.1%), ND3 (8.6%), and ND5 (6.6%) . Serovars 1, 3, 6, C, D, and new serovars ND1 and ND2 were infrequently identified, and 15.2% of isolates were nontypeable . It was not uncommon to isolate multiple serovars from swine of the same herd or related herds . Distribution of serovars among isolates from the United States and Canada was generally similar; however, a higher prevalence of serovar 5 and a lower prevalence of serovars 2, ND3, and ND5 were evident in isolates from Canada . Comparison of isolates obtained from the respiratory tract of swine without polyserositis with those obtained from swine with polyserositis revealed an increased frequency of serovars 4 and 5, and a decreased frequency of serovar 2, among isolates from swine with polyserositis . However, all prevalent serovars were isolated from swine with polyserositis, and data were not indicative of an association between serovar, site of isolation, or pathogenic potential. Jpn J Antibiot, 1992 May, 45(5), 539 - 47 {Sputum penetration of levofloxacin and its clinical efficacy in patients with chronic lower respiratory tract infections}; Nakamori Y et al.; Sputum penetration of levofloxacin (LVFX) was evaluated after a single oral dose of 100 mg or 200 mg to 4 patients with copious purulent sputa . The sputum concentration of LVFX reached maximum levels of 1.27 and 4.36 micrograms/ml at 4 hours, and still remained at concentrations of 0.32 and 1.68 micrograms/ml at 8 hours after administration of 100 mg and 200 mg, respectively . The AUC ratio of sputum/serum was 0.9-1.0, indicating good sputum penetration of LVFX in these patients . The clinical efficacy and the safety of LVFX were also evaluated in a total of 13 patients with respiratory tract infections associated with bronchiectasis, diffuse panbronchiolitis, etc . LVFX was administered orally at a daily dose of 200 mg once a day, 100 mg t.i.d . or 200 mg t.i.d . for 7-28 days (mean 14.7 days) . The clinical response to the drug was rated as excellent in 1 case, good in 5, fair in 3, and poor in 2 cases in 11 evaluable cases, thus the efficacy rate was 54.5% . All the 3 strains of Haemophilus influenzae were eradicated . Of the 3 strains of Pseudomonas aeruginosa, eradication, decrease, and unchange was observed for 1 strain each . One strain of Streptococcus pneumoniae remained unchanged . No adverse reaction was observed except for 1 case with slight and temporary increase of eosinophils . The above results suggested that LVFX would be clinically useful in the treatment of chronic lower respiratory tract infections. Infection, 1992 May-Jun, 20(3), 176 - 82 Comparison of loracarbef (LY163892) versus amoxicillin in the treatment of bronchopneumonia and lobar pneumonia; Muller O et al.; Loracarbef (LY163892), a carbacephem, is the first of a new class of beta-lactam compounds . A 14-day, double-blind, randomized, parallel treatment study compared loracarbef (400 mg b.i.d.; n = 169) and amoxicillin (500 mg t.i.d.; n = 167) in the treatment of lobar pneumonia and bronchopneumonia . Forty-four patients in the loracarbef group and 40 patients in the amoxicillin group were evaluable for efficacy analysis . Streptococcus pneumoniae and Haemophilus influenzae were isolated from pure or mixed cultures in 45.5% of the evaluable patients, with S . pneumoniae being isolated most frequently . Favourable clinical responses (cure or improvement) in the loracarbef-treated group (42/44; 95.5%) were similar to those in the amoxicillin-treated group (38/40; 95%) . A favourable bacteriological response was observed for 36/44 (81.8%) loracarbef-treated patients compared with 28/40 (70%) amoxicillin-treated patients (p = 0.2) . Adverse events were similar in both groups . Withdrawal of treatment was required in three patients in each group due to gastrointestinal events or rash/allergic exanthema . These data support the conclusion that loracarbef and amoxicillin have comparable efficacy and safety in the treatment of bronchopneumonia and lobar pneumonia caused by susceptible pathogens . However, loracarbef can be administered twice daily, offering the advantage of improved patient compliance . It is also active against beta-lactamase producing organisms. Kansenshogaku Zasshi, 1992 May, 66(5), 561 - 7 {The long-term chemotherapy with erythromycin (EM) in chronic lower respiratory tract infections--third report: clinical study of cases administered EM over 3 years}; Mikasa K et al.; An investigation was made of the use of EM therapy which began in 1986 or earlier in 31 cases with chronic lower respiratory tract infections . 1) Of the 20 cases in which EM (Erythromycin stearate) administration (600-1200 mg/day) was continued for 3 years or more and its usefulness could be evaluated, treatment with this agent was judged markedly effective in three, effective in 14, somewhat effective in two, and ineffective in one . This amounted to an effectiveness rate (effective or better) of 85% . 2) Improved QOL was observed in 15 of the 20 cases . 3) In the Pseudomonas infected cases, a discrepancy was seen between the effectiveness rate of 87.5% and the disappearance rate of the organism (12.5%), while in the Haemophilus cases no such discrepancy was found (75%) . 4) EM administration was stopped in 11 cases because of side effects in two (stomatitis, gastrointestinal disorder) death in five, desire of the patient in three, and transfer to another hospital in one . The cause of death cases had no connection with administration of EM . 5) In the three patients who stopped EM on their own, the agent was again administered because of exacerbation of symptoms, although this readministration proved ineffective in two of the cases . The above results suggest that long term EM therapy is useful and that its continued administration is important. Infection, 1992 May-Jun, 20(3), 164 - 7 In vitro activity of clarithromycin and its 14-hydroxy-metabolite against 203 strains of Haemophilus influenzae; Bergeron MG et al.; The in vitro activity of clarithromycin alone and in combination with its primary human metabolite, 14-hydroxy-clarithromycin, was determined against 203 strains of Haemophilus influenzae . Microdilution broth MICs and MBCs of both clarithromycin and 14-hydroxy-clarithromycin were determined . The clarithromycin MIC50 was 4 mg/l and the MIC90 was 8 mg/l . The hydroxy metabolite was 2-4-fold more active with an MIC50 and MIC90 of 2 mg/l . The MBCs were equal to the MICs . The microbicidal effect of combinations of clarithromycin and 14-hydroxy-clarithromycin was tested using a microdilution checkerboard technique and the fractional inhibitory index was calculated . The combination was additive in 92% and synergistic in 8% of all strains of H . influenzae tested; no antagonism was found . The results were independent of the site of isolation of the strain or presence of beta-lactamase . These findings suggest the potential clinical utility of clarithromycin for the treatment of H . influenzae infections. J Infect Dis, 1992 May, 165(5), 865 - 72 Haemophilus influenzae lipopolysaccharide disrupts confluent monolayers of bovine brain endothelial cells via a serum-dependent cytotoxic pathway; Patrick D et al.; An in vitro blood-brain barrier (BBB) model consisting of primary cultures of bovine brain microvascular endothelial cells was used to examine the effect of Haemophilus influenzae type b (Hib) on the BBB . Whole bacteria and purified lipopolysaccharide (LPS; greater than 10 ng/ml) caused marked cytotoxicity on the bovine brain endothelial cells . This effect could be completely blocked by polymyxin B . Similar cytotoxic effects were observed with a cultured bovine pulmonary endothelial cell line . Serum was essential for the LPS-mediated cytotoxic effect, and human, horse, bovine, or fetal calf serum all had similar effects . The serum factor was not a complement component . A monoclonal antibody against CD14, a receptor involved in mediating the effect of LPS in monocytes, completely blocked the cytotoxic effect in both brain and pulmonary endothelial cells . These results suggest that Hib LPS disrupts an in vitro BBB model via a serum- and CD14-dependent pathway and that LPS has cytotoxic effects on bovine endothelial cells without the involvement of monocytic cells, an effect that may be important in gram-negative meningitis and in endotoxic shock. J Bacteriol, 1992 May, 174(9), 2913 - 21 A comparative genetic study of serologically distinct Haemophilus influenzae type 1 immunoglobulin A1 proteases; Poulsen K et al.; The bacterial immunoglobulin A1 (IgA1) proteases are putative virulence factors secreted by a number of human pathogens capable of penetrating the mucosal barrier . Among Haemophilus influenzae strains, the IgA1 protease is found in several allelic forms with different serological neutralizing properties . A comparison of the primary structures of four serologically distinct H . influenzae IgA1 proteases suggests that this variation is caused by epitopes of the discontinuous conformational type . Analysis of the homologies among the four iga genes indicates that the variation results from transformation and subsequent homologous recombination in the iga gene region among H . influenzae strains . We find evidence for gene rearrangements, including transpositions in the iga gene region encoding the secretory part of the IgA1 preprotease . The amino acid sequence of the C terminus of the preprotease (the beta-core), which is assumed to be involved in secretion of the protease by forming a pore in the outer membrane, is highly conserved . In contrast to conserved areas in the protease domain, the nucleotide sequence encoding the beta-core showed a striking paucity of synonymous site variation. Infect Immun, 1992 May, 60(5), 2016 - 22 Neonatal, urogenital isolates of biotype 4 nontypeable Haemophilus influenzae express a variant P6 outer membrane protein molecule; Murphy TF et al.; The P6 outer membrane protein is a highly conserved molecule which is present on the surface of all strains of Haemophilus influenzae . Sixty strains of nontypeable H . influenzae which caused invasive disease or colonized the female urogenital tract were studied with monoclonal antibodies 7F3 and 4G4, which recognize different surface-exposed epitopes on the P6 molecule . All 60 strains expressed the epitope recognized by 4G4, whereas 47 of 60 strains expressed the epitope recognized by antibody 7F3 . The 7F3-nonreactive strains were all biotype 4 and were recovered from the blood of neonates or postpartum women or from the female urogenital tract . The P6 genes from two 7F3-nonreactive strains were cloned, and the nucleotide sequences were determined . Analysis of amino acid sequences, immunoassays with synthetic peptides, and site-directed mutation of the P6 gene indicate that the epitope recognized by antibody 7F3 is conformational and that the sequence Asp-Ile-Thr is critical in maintaining the conformation of the epitope . We conclude that the unusually virulent clone family of biotype 4 strains of nontypeable H . influenzae express a variant P6 molecule which has an alteration in a highly conserved surface-exposed epitope. Eur J Clin Microbiol Infect Dis, 1992 May, 11(5), 462 - 5 Interpretive criteria for CI-960, fleroxacin and temafloxacin susceptibility tests with Haemophilus influenzae; Barrett MS et al.; Haemophilus influenzae strains with varied ampicillin resistance and beta-lactamase production patterns were tested against three investigational fluorinated quinolones (CI-960, fleroxacin, temafloxacin) using Haemophilus Test Medium (HTM) and National Committee for Clinical Laboratory Standards (NCCLS) methods . The disk diffusion zones and MICs were compared and regression statistics and scattergrams generated . The rank order of the agents according to activity against Haemophilus influenzae was CI-960 (MIC50 0.002 microgram/ml) greater than temafloxacin (MIC50 0.015 microgram/ml) greater than fleroxacin (MIC50 0.03 microgram/ml) . The recommended susceptibility interpretive criteria for the 5-micrograms disks of each drug were: for CI-960 greater than or equal to 23 mm (MIC correlate less than or equal to 1 microgram/ml); for fleroxacin greater than or equal to 19 mm (MIC correlate less than or equal to 2 micrograms/ml); and for temafloxacin greater than or equal to 16 mm (MIC correlate less than or equal to 2 micrograms/ml) . All recent Haemophilus influenzae isolates tested were susceptible to these potent fluoroquinolones and no interpretive errors were observed. Diagn Microbiol Infect Dis, 1992 May-Jun, 15(4), 277 - 80 Assessment of gelatin-supplemented BACTEC blood culture medium in a pediatric hospital; McDonald JC et al.; Sodium polyanetheolesulfonate (SPS), an anticoagulant used in blood culture media, adversely affects the isolation of Neisseria meningitidis . The addition of gelatin appears to counteract this effect . Studies using the radiometric BACTEC system, however, have noted a lower isolation rate of other bacteria from gelatin-supplemented media . We wished to evaluate the effect of the addition of gelatin (1.2%) to a nonradiometric BACTEC aerobic medium (NR6A) on the recovery of N . meningitidis and other pathogens . The NR6A medium with gelatin (NR6A analogue) also contained a lower concentration of SPS (0.025% vs 0.035%) . We did 6045 paired comparisons of blood cultured in routine NR6A medium and the NR6A analogue . Eight isolates of N . meningitidis were recovered, five only from the gelatin-supplemented medium and three from both bottles . There was no statistically significant difference in total recovery of aerobic and facultative bacteria or Candida species from both bottles . Haemophilus influenzae was detected earlier in the nonsupplemented NR6A medium . We conclude that the use of the NR6A analogue medium appeared to increase the yield of N . meningitidis without adversely affecting the recovery of other common pathogens, although the recovery of H . influenzae was slightly delayed. Med J Aust, 1992 Apr 20, 156(8), 569 - 72 Invasive Haemophilus influenzae infection in the Australian Capital Territory region; McGregor AR et al.; OBJECTIVE: To investigate the pattern of invasive Haemophilus influenzae disease in the Australian Capital Territory (ACT) region with a view to assessing the possible benefits of vaccination in this community . SETTING AND DESIGN: The microbiology department of Royal Canberra Hospital processes all specimens from the three public hospitals in the ACT . Together these hospitals provide all paediatric medical and approximately 80% of adult inpatient beds available in the ACT . We identified all laboratory isolates of H . influenzae obtained from normally sterile sites from 1984 to 1990, and reviewed the clinical records of these patients . Also included in this analysis were all cases of acute epiglottitis identified in hospital discharge summaries, intensive care and coroners' records . Epidemiological, clinical and microbiological data were gathered and assessed . RESULTS: We identified 138 cases of infection . Forty per cent (36 of 66 cases of meningitis, 5 of 44 cases of epiglottitis, 10 of 12 cases of cellulitis) occurred in children aged less than 18 months . Meningitis (48%), epiglottitis (32%), cellulitis (9%) and primary bacteraemia (4%) were the most common syndromes seen . The annual incidence of invasive H . influenzae disease in Canberra was 63.2 per 100,000 children aged under five years . Approximately 1 in 225 children under five years of age and resident in Canberra developed invasive H . influenzae disease . Ninety-eight per cent of isolates serotyped were type b . CONCLUSION: A vaccination program effective in preventing H . influenzae type b infection, completed in infants before 6 months of age, could prevent upwards of 80% of invasive H . influenzae disease in our population . Such a program should be cost effective although precise assessment is hampered by the lack of accurate data on the acceptance rate, costs and efficacy of the current childhood vaccination schedule in our region. J Immunol Methods, 1992 Apr 8, 148(1-2), 101 - 14 Quantitation of human IgG subclass antibodies to Haemophilus influenzae type b capsular polysaccharide . Results of an international collaborative study using enzyme immunoassay methodology; Herrmann DJ et al.; An international collaborative study was conducted at ten sites to examine the performance of enzyme immunoassays (EIAs) for the quantitation of IgG1, IgG2, IgG3, IgG4 and total IgG anti-Haemophilus influenzae type b (Hib) capsular polysaccharide in human serum . All groups used the same reagents: microtiter plates coated with polyribosylribitol phosphate (PRP) conjugated to poly-L-lysine (PLL), reference, control and test human sera, biotin-conjugated International Union of Immunological Societies (IUIS)-documented monoclonal anti-human IgG1-4 and IgG Pan detection antibodies, avidin-peroxidase and TMB substrate . Initial mixing of soluble PRP antigen or an equal volume of buffer with the 20 test sera prior to analysis confirmed PRP antigen specificity in all five EIAs with greater than 80% competitive inhibition at most sites . Positive correlation between the total IgG anti-Hib and sum of IgG1-4 anti-Hib was demonstrated (r2 = 0.99, Y = 1.13X -0.15) . Good agreement was shown between the total IgG anti-Hib as measured by EIA and the total Hib-specific antibodies measured by the current radiolabeled antigen binding assay (r2 = 0.97, Y = 4.6X -5.8) . Assay parallelism was demonstrated with an average interdilutional %CV of 22% and parallel dose-response curve slopes . The interdilutional %CVs were calculated as an average per sample of the variation of microgram/ml (corrected for dilution) at different dilutions per laboratory for all participating sites . The interlaboratory variation was the only performance parameter studied that exceeded the target level of 35% CV in all IgG1-4 and total IgG anti-Hib assays . IgG subclass distributions in the test sera demonstrated a predominance of IgG1 anti-Hib in the pediatric serum pools and IgG2 anti-Hib in the adult sera, with low but detectable levels of IgG3 and IgG4 anti-Hib in each group. Am J Med, 1992 Apr 6, 92(4A), 98S - 102S A double-blind study of two dosage regimens of lomefloxacin in bacteriologically proven exacerbations of chronic bronchitis of gram-negative etiology; Kemper P et al.; Lomefloxacin has been shown to produce high and sustained concentrations in serum and bronchial mucosa after once-daily administration . This study was designed to assess whether a dose response exists for 400 mg lomefloxacin given once daily or twice daily for 10 days in the treatment of acute bacterial exacerbations of chronic bronchitis of gram-negative etiology . A total of 100 adult patients with acute exacerbations of chronic bronchitis were enrolled at 10 study sites in Germany . Patients with confirmed bacterial pathogens in the baseline sputum culture (once-daily group n = 49, twice-daily group n = 47) were eligible for analysis of bacteriologic and clinical efficacy . The eradication rates for the most frequently isolated baseline pathogens, Haemophilus influenzae, Pseudomonas aeruginosa, and Klebsiella pneumoniae, were at least 75% for both treatment regimens . Overall, once-daily treatment eradicated baseline pathogens in 42 of 49 (85.7%) patients, while twice-daily treatment eradicated pathogens in 43 of 47 (91.5%) . This difference was not statistically significant (p = 0.226) . Clinically, 47 of 49 (95.9%) patients in the once-daily group and 46 of 47 (97.9%) in the twice-daily group were cured or improved (p = 0.307) . Both regimens were well tolerated; there were no differences in the incidence (six patients in each group), types, or severity of adverse events, nor was there clinical evidence of theophylline interaction . The results of this study demonstrate that once-daily treatment with 400 mg lomefloxacin is as effective as twice-daily dosing with 400 mg in patients with acute bacterial exacerbations of chronic bronchitis. Am J Med, 1992 Apr 6, 92(4A), 58S - 62S Lomefloxacin: microbiologic assessment and unique properties; Mayer KH et al.; In comparative studies, lomefloxacin, a new difluorinated quinolone, exhibits broad antibacterial activity in vitro, similar or superior to that of other quinolones (enoxacin, ofloxacin, pipemidic acid, nalidixic acid, and norfloxacin) but less than that of ciprofloxacin . Lomefloxacin inhibited Neisseria gonorrhoeae, Moraxella (Branhamella) catarrhalis, Haemophilus influenzae, Pseudomonas aeruginosa, Staphylococcus aureus, and the majority of aerobic gram-negative rods, including nosocomial isolates, at concentrations readily achievable in biologic fluids and tissues . Lomefloxacin was less active against obligate anaerobes and streptococci . Organisms resistant to methicillin, penicillin, or the aminoglycosides were susceptible to lomefloxacin . No significant lomefloxacin resistance was identified in 18 countries in which in vitro studies were conducted, with the exception of a small number of strains tested in France . The frequency with which spontaneous single-step resistance to lomefloxacin develops in vitro is low. Am J Med, 1992 Apr 6, 92(4A), 108S - 113S Safety and efficacy of lomefloxacin versus cefaclor in the treatment of acute exacerbations of chronic bronchitis; Gotfried MH et al.; In two multicenter trials, lomefloxacin and cefaclor were compared as treatments for acute bacterial exacerbations of chronic bronchitis . In total, 522 adult outpatients were enrolled at 50 centers in the United States . Patients were randomized to treatment groups receiving either 400 mg lomefloxacin orally once daily (n = 259) or 250 mg cefaclor every 8 hours (n = 263) for 7-10 days . Both groups were comparable in terms of age, severity of exacerbation, smoking history, theophylline use, and baseline pathogens . The most common baseline pathogens were Haemophilus influenzae, found in 32% of patients in the lomefloxacin group and in 29% in the cefaclor group, Pseudomonas aeruginosa (13% and 16%, respectively), Moraxella (Branhamella) catarrhalis (12% and 13%), and Streptococcus pneumoniae (10% in both groups) . Bacterial eradication rates 1-4 days after the completion of treatment for all patients with baseline pathogens were 81.8% in the lomefloxacin group and 62.7% in the cefaclor group (p less than 0.001) . Clinical success (disappearance or improvement of presenting signs and symptoms) was noted in 80.0% of patients in the lomefloxacin group and 64.7% in the cefaclor group (p = 0.002) . Eradication rates for the subgroup of patients who had pathogens susceptible in vitro to both study drugs and who completed treatment were 97.1% for lomefloxacin and 84.6% for cefaclor (p = 0.002) . Clinical success rates in this subgroup were 92.4% for lomefloxacin and 90.1 for cefaclor (p = 0.585) . Treatment-related adverse events were reported for 7% of patients in the lomefloxacin group and 5% in the cefaclor group . The most common adverse events in both groups were nausea and diarrhea . Six patients were withdrawn from treatment with lomefloxacin and four from the cefaclor group because of adverse events . There was no clinical or laboratory evidence of theophylline interaction with either treatment . Once-daily oral administration of 400 mg lomefloxacin was an effective, well-tolerated alternative to 250 mg of cefaclor three times daily in the treatment of acute exacerbations of chronic bronchitis. J Biol Chem, 1992 Apr 5, 267(10), 6859 - 64 Site-specific integration of the Haemophilus influenzae bacteriophage HP1 . Identification of the points of recombinational strand exchange and the limits of the host attachment site; Hauser MA et al.; Isotopic transfer experiments and boundary replacement studies were used to define the size and cleavage points of the Haemophilus influenzae attB site for phage HP1 integration . The points of strand cleavage and transfer were separated by 5' extensions with a spacing or overlap region most probably 7 residues long . The complete HP1 attB site is included within an 18-base pair (bp) sequence surrounding the cleavage sites . The sequence of HP1 attB is remarkably symmetric . Two 8-bp inverted repeats surround the central residue of the 7-bp overlap sequence; this central residue is the second residue of the anticodon sequence of the H . influenzae tRNA(leu)(UUR) gene which contains attB, and this symmetric segment encodes the anticodon stem and loop. Ther Umsch, 1992 Apr, 49(4), 234 - 8 {Pneumonia: etiologic diagnosis and therapy in general practice}; Bille J et al.; The majority of community-acquired pneumonias are not hospitalized, have a good prognosis and a low mortality rate . In the nonimmunocompromised adult patient, pneumonias are caused by a broad array of microorganisms of which the so-called 'atypical' agents (mycoplasma, chlamydiae, viruses) are as frequently found as classical bacteria such as pneumococci and haemophilus . Generally, the mode of acquisition and the clinical picture will not allow to deduct the etiology with certainty, and the laboratory results are often nonconclusive (sputum examination) or delayed (serology) . Empirical therapy should be initiated based on epidemiological grounds and on the characteristics of the patient . For patients without underlying conditions, immunosuppression or advanced age, a macrolide (erythromycin or a new macrolide) appears to constitute a good choice because of its broad spectrum of activity, comprising the classical bacterial agents of pneumonia, mycoplasma, chlamydiae, and legionella. Hybridoma, 1992 Apr, 11(2), 257 - 66 Spontaneous hybridoma formation induced by immunization with Haemophilus paragallinarum: evidence for a lipopolysaccharide fusion inducer; Boshoff CH et al.; The phenomenon of spontaneous fusion between myeloma cells and splenocytes from mice immunized with formalin-inactivated Haemophilus paragallinarum cells, has been reported on recently (1) . The identity and properties of the bacterial inducer of fusogenicity of splenocytes have been further investigated with the aid of a monoclonal antibody VF3 against H . paragallinarum (2), which has a bacterial strain specificity correlating with the ability of the strains to induce spontaneous fusion between splenocytes of immunized mice and myeloma cells . It was shown that the lipopolysaccharide fraction of the bacteria was required for the induction of fusogenicity . LPS involvement was clearly indicated by the parallel effects on VF3 antigenicity and fusogenic inductivity of various treatments such as proteolytic digestion, periodate oxidation and sensitivity towards alkali, acid or freezing. Can J Vet Res, 1992 Apr, 56(2), 127 - 34 Isolation of pathogenic strains of Haemophilus somnus from the female bovine reproductive tract; Kwiecien JM et al.; The prevalence of Haemophilus somnus in the genital tract of slaughtered and live cows in southern Ontario was investigated . The vagina and uterus of slaughtered cows were swabbed separately . Live cows were examined and sampled in two field surveys: Centre A and Centre B . In the former, aspirated mucus secretions and in the latter, specimens obtained by guarded swabbing were examined bacteriologically . Haemophilus somnus was isolated from 28 genital tracts of 461 slaughtered (6.1%), and seven of 199 live (3.5%) cows during the centre B survey . The isolates were recovered from both normal and diseased reproductive tracts . Fourteen strains isolated from genital organs were examined for pathogenicity in vivo to test the occurrence of pathogenic isolates . In the initial stage of the in vivo study on pathogenicity, each of the fourteen isolates was examined on one calf using an intracisternal inoculation . Subsequently, one pathogenic and one nonpathogenic strain were inoculated into five calves each to statistically confirm their pathogenic potential . Of 14 genital isolates of H . somnus examined in an intracisternal calf assay, six (43%) caused a fatal peracute neurological disease, while eight were nonpathogenic . A comparative pathological study of pathogenic and nonpathogenic isolates showed that the former caused a severe fatal suppurative meningoencephalitis whereas the latter caused no lesions whatsoever or a mild leukocytic leptomeningitis . The salient data obtained in this study indicate that there are pathogenic strains of H . somnus in the genital tract of apparently normal cows as well as of those with inflammatory disease. Arch Dis Child, 1992 Apr, 67(4), 475 - 8 Immunogenicity and safety of PRP-T conjugate vaccine given according to the British accelerated immunisation schedule; Booy R et al.; The immunogenicity and safety of a new Haemophilus influenzae type b conjugate vaccine, PRP-T, was studied in 107 infants from the Oxford district . The vaccine was given concurrently with diphtheria, pertussis, tetanus, and polio vaccines at 2, 3, and 4 months of age . Symptoms after immunisation were recorded by a parent . Sera were obtained before the first immunisation and at 5 months of age and the antibodies were measured by both radioimmunoassay and enzyme linked immunosorbent assay (ELISA) . No serious adverse reactions were observed and there was no increase in the incidence of expected minor side effects . By radioimmunoassay, the geometric mean titre of serum anticapsular antibody increased from 0.09 micrograms/ml before immunisation to 5.01 micrograms/ml after three immunisations . Ninety eight per cent of children had antibody concentrations consistent with protection (greater than or equal to 0.15 micrograms/ml) . IgG antibody concentrations measured by ELISA correlated well with total antibody concentrations measured by radioimmunoassay (r = 0.864) . These results provide encouragement that routine immunisation against H influenzae type b at 2, 3, and 4 months of age, could prevent most cases of disease in children in the UK. Can J Cardiol, 1992 Apr, 8(3), 303 - 5 Cardiac tamponade secondary to haemophilus pericarditis: a case report; Welikovitch L et al.; Pyogenic pericarditis is encountered uncommonly in clinical practice . The majority of cases of clinically apparent pericarditis are viral in origin . When bacterial infection of the pericardial space does occur the causative organism is usually Staphylococcus or Streptococcus species . Isolation of an haemophilus organism from the pericardial space in this condition is distinctly unusual . There are only 10 previously reported cases in the literature of pericarditis secondary to Haemophilus influenzae . This report describes the case of a 36-year-old woman who presented with haemophilus empyema and purulent pericarditis progressing to cardiac tamponade . There are isolated reports of successful treatment of pyogenic pericarditis with closed drainage and antibiotics . In the absence of clear evidence demonstrating the efficacy of this approach the authors favour open exploration of the pericardial space. J Clin Microbiol, 1992 Apr, 30(4), 961 - 6 Multicenter evaluation of the use of Haemophilus test medium for broth microdilution antimicrobial susceptibility testing of Streptococcus pneumoniae and development of quality control limits; Jorgensen JH et al.; A five-laboratory collaborative study was undertaken to determine the precision and accuracy of broth microdilution susceptibility tests of Streptococcus pneumoniae isolates performed with Haemophilus test medium (HTM) compared with tests performed with lysed horse blood-supplemented Mueller-Hinton broth (LHB) . The intra-and interlaboratory reproducibilities of MICs of 10 antimicrobial agents determined with the two media were found to be quite similar and highly reproducible in both media . On the basis of favorable performance in this study, S . pneumoniae ATCC 49619 is recommended as a quality control strain to assess the performance of HTM when this medium is used for testing of pneumococci . Testing of 293 unique clinical isolates of S . pneumoniae with both media in the respective participant laboratories allowed a direct comparison of MIC results and a calculation of interpretive error rates . Although there were some slight differences between MICs determined with HTM and MICs determined with LHB, few very major or major errors resulted from testing the clinical isolates against the 10 antimicrobial agents . However, MIC-interpretive criteria specific for S . pneumoniae should be developed and promulgated through a national consensus mechanism. J Clin Microbiol, 1992 Apr, 30(4), 862 - 5 Designation of 15 serovars of Haemophilus parasuis on the basis of immunodiffusion using heat-stable antigen extracts; Kielstein P et al.; Previous independent investigations of the serotyping of Haemophilus parasuis strains have led to the designation of serovars A to D, 1 to 7, Jena 6 to Jena 12, and ND1 to ND5 . Heat-stable antigen preparations from the reference strains for these serovars were tested by immunodiffusion with rabbit hyperimmune antisera . The existence of 15 distinct serologic groups was apparent, for which we propose the designations serovars 1 to 15 . Examination of 290 field isolates from swine in the former German Democratic Republic indicated a prevalence of serovars 4 and 5, which together accounted for 41% of the isolates examined . However, 26.2% of the isolates were nontypeable with this test procedure and available antisera . Intraperitoneal inoculation of specific-pathogen-free pigs with cells representing the 15 serovars indicated differences in virulence which may be serovar related . Cells of strains representing serovars 1, 5, 10, 12, 13, and 14 were the most virulent, causing death or moribundity in inoculated pigs . Cells of serovars 2, 4, 8, and 15 caused polyserositis, but not death, in inoculated pigs . However, inoculation of cells of strains representing serovars 3, 6, 7, 9, and 11 resulted in no clinical symptoms or lesions indicative of H . parasuis infection. Clin Pharm, 1992 Apr, 11(4), 332 - 6 New considerations for Haemophilus influenzae type b vaccination; Pinson JB et al.; The immunogenicity, efficacy, adverse effects, dosage recommendations, and cost of the three commercially available Haemophilus influenzae type b (Hib) conjugate vaccines are discussed . Three Hib conjugate vaccines are licensed for use in children 15 months of age or older: ProHIBiT (Connaught), HibTITER (Praxis), and PedvaxHIB (Merck) . HibTITER and PedvaxHIB were recently approved for use in infants as young as two months of age; both have demonstrated efficacy in preventing Hib disease in this age group, whereas ProHIBIT has not been shown to afford adequate protection in young infants . Because the three vaccines induce markedly different immunologic responses, they cannot be considered interchangeable and the recommended dosage schedules differ . The Centers for Disease Control Immunization Practices Advisory Committee (ACIP) and the American Academy of Pediatrics (AAP) both recommend that all infants be immunized with a complete series of either HibTITER or PedvaxHIB beginning routinely at two months or as soon as possible thereafter . The cost of a single dose is similar for the three Hib conjugate vaccines; full immunization with HibTITER is more expensive than with ProHIBiT or PedvaxHIB because four doses are required for completion of the series . Selection of the appropriate Hib vaccine for infants should be based on availability, cost, and the clinician's interpretation of existing data. Clin Pediatr (Phila), 1992 Apr, 31(4), 221 - 7 Precise quantification of fever in childhood bacterial meningitis; Anttila M et al.; Precise quantity of fever was determined in 191 cases of childhood bacterial meningitis by calculating the areas between the line indicating 37.8 degrees C or 39.5 degrees C temperature and the line connecting all individual temperature values . Temperature measurements were performed rectally one to four times a day throughout the hospitalization . The obtained areas under the curves (AUC), expressed as degree-hours, proved to be a sensitive index for delineating each individual fever pattern and reflected the magnitude of fever more precisely than the traditional fever curves . Children under five had significantly (p less than 0.05) greater AUC than those at five to 15 years; similarly, patients with Haemophilus influenzae meningitis showed greater AUC (i.e., had more fever) than those with meningococcal disease (p less than 0.05) . The overall rates of secondary (14%), persistent (16%), and prolonged fever (8%) were virtually identical to previous reports; no drug fever was reported in this study . In cases with prolonged fever, a significantly higher rate (40%) of neurological complications was found compared to those who became afebrile earlier . This method is potentially utilizable in other diseases and conditions where precise measurement of fever is of clinical or scientific relevance. J Med Microbiol, 1992 Apr, 36(4), 279 - 82 Biotypes of Haemophilus parainfluenzae from the respiratory secretions in chronic bronchitis; Taylor DC et al.; A total of 2401 isolates of Haemophilus parainfluenzae was isolated from respiratory secretions of 36 healthy adults and 128 patients with chronic bronchitis over a period of 1 year . The isolates were allocated to eight biotypes, by their production of indole, urease and ornithine decarboxylase . Biotypes I and II constituted most of the isolates of H . parainfluenzae from the oropharynx of controls (75%) and chronic bronchitics (c . 90%) . Among the patients, there was no difference in the isolation rate between oropharyngeal swabs and sputum specimens . Biotypes III, IV, VI, VII and VIII were isolated less frequently, as was a new taxon defined here as biotype V which does not produce indole, urease or ornithine decarboxylase . Biotype III was isolated significantly less frequently from cases of chronic bronchitis than from controls, whereas biotype II was isolated somewhat more frequently from the patients, especially during acute episodes. Am Fam Physician, 1992 Apr, 45(4), 1759 - 72 Childhood immunizations: a practical approach for clinicians; Zimmerman RK et al.; Family physicians can play a key role in reversing the resurgence of vaccine-preventable illnesses by making sure that patients are fully immunized . Childhood immunization schedules have recently changed . A second dose of measles, mumps and rubella (MMR) vaccine should be given at age four to six years . It has been recommended that hepatitis B vaccine be administered routinely to all infants in the United States . Both hepatitis B vaccine and hepatitis B immunoglobulin should be given to offspring of hepatitis B carriers . Haemophilus b conjugate vaccine (HbCV) should be administered to all infants, beginning at two months of age . Vaccines can be safely administered to patients with mild illnesses, allergic rhinitis, low-grade fever or penicillin allergy, as well as to those taking antibiotics . If indicated, several vaccines, such as diphtheria, tetanus and pertussis, oral poliovirus, HbCV and MMR, can be given simultaneously. J Bacteriol, 1992 Apr, 174(8), 2425 - 30 Identification of two iron-repressed periplasmic proteins in Haemophilus influenzae; Harkness RE et al.; Protein expression by Haemophilus influenzae under iron-limiting growth conditions was examined . The five type b strains and four nontypeable strains studied all expressed a new protein of about 40 kDa when deprived of iron during growth . Most strains also expressed a protein of about 31 kDa under the same growth conditions . Both the 40- and 31-kDa proteins were not expressed by cells grown in iron-replete medium . The 40- and 31-kDa proteins were not expressed in iron-deficient medium to which an excess of ferric nitrate had been added, and therefore it was concluded that their expression was iron regulated . These iron-repressed proteins were localized to the periplasmic space . The amino-terminal sequences of both proteins were determined . The N-terminal sequence of the 40-kDa protein had 81% similarity to the N terminus of Fbp, the major iron-binding protein of Neisseria gonorrhoeae and N . meningitidis . The 31-kDa protein sequence showed no homology with any known protein sequence . As no plasmids were found in the strains, it was concluded that these proteins were chromosomally encoded. J Infect Dis, 1992 Apr, 165(4), 753 - 6 Correlation between antibody affinity and serum bactericidal activity in infants; Hetherington SV et al.; Nearly one-half of infants immunized with Haemophilus influenzae b capsular polysaccharide (polyribosylribitol phosphate; PRP)-protein conjugate produce low-affinity antibody . To test the hypothesis that antibody affinity is linked to biologic function, sera were obtained before and 1 month after immunization of 18-month-old infants with PRP-diphtheria toxoid conjugate vaccine . Correlation was attempted of anti-PRP affinity, concentrations of anti-PRP, and anti-outer membrane proteins and of immunoglobulin isotype with bactericidal activity . Nine subjects produced anti-PRP of low affinity (K less than 10(4) l/mol), and 11 had higher affinity antibodies (average K, 2.8 x 10(4) l/mol) . By multiple regression analysis, antibody affinity was the only variable significantly related to the bactericidal activity of serum after immunization with the conjugate vaccine (r = .71; P = .04) . Thus, serum anti-PRP from a substantial proportion of infants appeared functionally deficient in association with low-affinity antibody. Infect Immun, 1992 Apr, 60(4), 1336 - 42 Protein D, the immunoglobulin D-binding protein of Haemophilus influenzae, is a lipoprotein; Janson H et al.; Protein D is an immunoglobulin D-binding membrane protein exposed on the surface of the gram-negative bacterium Haemophilus influenzae . Results reported here indicate that protein D is a lipoprotein . The protein is apparently synthesized as a precursor with an 18-residue-long signal sequence modified by the covalent attachment of both ester-linked and amide-linked palmitate to the cysteine residue, which becomes the amino terminus after cleavage of the signal sequence . Globomycin inhibited maturation of protein D in H . influenzae, implying that protein D is exported through the lipoprotein export pathway . A mutant expressing a protein D lacking the cysteine residue was constructed by oligonucleotide site-directed mutagenesis . The mutated protein D molecule was not acylated and partitioned in the aqueous phase after Triton X-114 extraction of intact bacteria, unlike native and recombinant protein D, which partitioned in the detergent phase . The nonacylated protein D molecule was localized to the periplasmic space of Escherichia coli . The hydrophilic protein D molecule will be used in investigations concerning its ability to function as a vaccine component. Infect Immun, 1992 Apr, 60(4), 1302 - 13 Cloning, expression, and DNA sequence analysis of genes encoding nontypeable Haemophilus influenzae high-molecular-weight surface-exposed proteins related to filamentous hemagglutinin of Bordetella pertussis; Barenkamp SJ et al.; A group of high-molecular-weight surface-exposed proteins of nontypeable Haemophilus influenzae are major targets of human serum antibody (S . J . Barenkamp and F . F . Bodor, Pediatr . Infect . Dis . J . 9:333-337, 1990) . To further characterize these proteins, we cloned and sequenced genes encoding two related high-molecular-weight proteins from a prototype nontypeable Haemophilus strain . The gene encoding a 120-kDa Haemophilus protein consisted of a 4.4-kbp open reading frame, and the gene encoding a 125-kDa protein consisted of a 4.6-kbp open reading frame . The first 1,259 bp of the two genes were identical . Thereafter, the sequences began to diverge, but overall they were 80% identical, and the derived amino acid sequences showed 70% identity . A protein sequence homology search demonstrated similarity between the derived amino acid sequences of both cloned genes and the derived amino acid sequence of the gene encoding filamentous hemagglutinin, a surface protein produced by the gram-negative pathogen Bordetella pertussis . Antiserum raised against a recombinant protein encoded by the 4.6-kbp open reading frame recognized both the 120- and the 125-kDa proteins in the prototype strain as well as antigenically related high-molecular-weight proteins in 75% of a collection of 125 epidemiologically unrelated nontypeable H . influenzae strains . The antiserum directed against the recombinant protein also recognized purified filamentous hemagglutinin . A murine monoclonal antibody to filamentous hemagglutinin recognized both the 120-kDa and the 125-kDa protein in the prototype strain as well as proteins identical to those recognized by the recombinant-protein antiserum in 35% of the nontypeable H . influenzae strain collection . Thus, we have identified and partially characterized a group of highly immunogenic surface-exposed proteins of nontypeable H . influenzae which are related to the filamentous hemagglutinin of B . pertussis. Jpn J Antibiot, 1992 Apr, 45(4), 443 - 51 {Pharmacokinetics and clinical studies of panipenem/betamipron in the pediatric field}; Fujisawa Y et al.; Panipenem/betamipron (PAPM/BP) is a mixture of panipenem (PAPM), carbapenem antibiotic, and betamipron (BP), N-benzoyl-beta-alanine . The adverse reaction to PAPM of the kidney is reduced by the addition of BP to PAPM which inhibits the anion transport in the kidney tubules . We studied the pharmacokinetics and the clinical efficacies of PAPM/BP in children and we evaluated the antibacterial activities of PAPM by determining MIC values of PAPM in vitro against organisms isolated in our children's hospital from January to December, 1990 . 1 . Pharmacokinetics 10 mg/kg of PAPM/BP (10 mg PAPM/10 mg BP) was administered intravenously by drip infusion to 7 children . The mean blood concentration of PAPM was 14.8 micrograms/ml at the peak, and the mean half life was 0.9 hours in blood . PAPM was not detected in blood 3 hours after the time when the peak values were attained . 2 . Clinical studies 10 mg/kg of PAPM/BP was administered intravenously 3 times a day to 18 cases including 15 of respiratory infections, 2 of otitis media and 1 of sepsis . The clinical efficacies of PAPM/BP were excellent or good in 17 out of the 18 cases . All causative organisms isolated in 5 cases, Methicillin-sensitive Staphylococcus aureus (MSSA) (1 case), Streptococcus pneumoniae (1), Haemophilus influenzae (2) and Branhamella catarrhalis (1) were eradicated in a few days upon the administrations of PAPM/BP . No adverse reactions due to PAPM/BP were observed, but a slight elevation of platelet counts in blood was observed in 1 case, which was normalized soon after the end of the treatment . 3 . Antibacterial activities in vitro(ABSTRACT TRUNCATED AT 250 WORDS) Infect Immun, 1992 Apr, 60(4), 1351 - 7 Stable, conserved outer membrane epitope of strains of Haemophilus influenzae biogroup aegyptius associated with Brazilian purpuric fever; Lesse AJ et al.; Brazilian purpuric fever is a rapidly fatal childhood disease associated with a clonal strain of Haemophilus influenzae biogroup aegyptius . We describe a conserved, surface-exposed epitope present on 95% of H . influenzae biogroup aegyptius isolates that are associated with Brazilian purpuric fever . This epitope, defined by reaction with the monoclonal antibody 8G3, is on or associated with the 48-kDa heat-modifiable P1 protein . The epitope is absent on strains of H . influenzae biogroup aegyptius that are not associated with Brazilian purpuric fever but is present on one strain of H . influenzae biotype II . None of 81 other Haemophilus strains tested reacted with 8G3 . The sensitivity and specificity of the 8G3 monoclonal antibody in detecting Brazilian case-clone strains of H . influenzae biogroup aegyptius associated with Brazilian purpuric fever are 95 and 99%, respectively . Immunoelectron microscopy revealed that the epitope is surface exposed, and N-terminal amino acid sequencing of an 8G3-reactive P1 protein from a strain of H . influenzae biogroup aegyptius showed 100% correlation with the published N-terminal amino acid sequence of a P1 protein of H . influenzae type b . The virulence of the organism in an infant rat model of bacteremia was not dependent on the expression of this epitope. Infect Immun, 1992 Apr, 60(4), 1322 - 8 Lipooligosaccharides (LOS) of some Haemophilus species mimic human glycosphingolipids, and some LOS are sialylated; Mandrell RE et al.; The lipooligosaccharides (LOS) of strains of Haemophilus ducreyi, Neisseria gonorrhoeae, Neisseria meningitidis, and Neisseria lactamica contain epitopes that are antigenically and structurally similar to carbohydrates present in human glycosphingolipids . LOS from strains of Haemophilus influenzae and H . influenzae biogroup aegyptius were tested for the binding of monoclonal antibodies (MAbs) that bind to human glycosphingolipids possessing Gal beta 1-4GlcNAc (MAb 3F11) and Gal alpha 1-4Gal beta 1-4Glc (MAb anti-Pk) . In solid-phase radioimmunoassays, the LOS of 18 of 19 H . influenzae type b (Hib), 8 of 19 nontypeable H . influenzae, and 10 of 20 H . influenzae biogroup aegyptius strains bound MAb anti-Pk . The LOS of 13 of 19 Hib, 10 of 16 nontypeable H . influenzae, and 2 of 18 H . influenzae biogroup aegyptius strains bound MAb 3F11 . Neuraminidase treatment of the strains increased the binding of MAb 3F11 by more than twofold in 47% of the H . influenzae strains, suggesting that sialic acid occluded the LOS structure recognized by MAb 3F11 . The material released from neuraminidase-treated Hib LOS was confirmed to be sialic acid by high-performance anion-exchange chromatography . A recombinant plasmid containing genes involved in Hib LOS biosynthesis directed the expression (assembly) of the 3F11 epitope in Escherichia coli . These studies demonstrate that H . influenzae and H . influenzae biogroup aegyptius express at least two LOS epitopes that are similar to those present in human glycosphingolipids . Sialic acid was present on the LOS of some H . influenzae strains and prevented the binding of MAb 3F11 to its epitope . The oligosaccharide portion of sialylated LOS may also resemble sialylated oligosaccharides present in human glycosphingolipids (gangliosides). EMBO J, 1992 Apr, 11(4), 1617 - 22 Conserved immunoglobulin-like features in a family of periplasmic pilus chaperones in bacteria; Holmgren A et al.; Detailed structural analyses revealed a family of periplasmic chaperones in Gram-negative prokaryotes which are structurally and possibly evolutionarily related to the immunoglobulin superfamily and assist in the assembly of adhesive pili . The members of this family have similar structures consistent with the overall topology of an immunoglobulin fold . Seven pilus chaperone sequences from Escherichia coli, Haemophilus influenzae and Klebsiella pneumoniae were aligned and their consensus sequence was superimposed onto the known three-dimensional structure of PapD, a representative member of the family . The molecular details of the conserved and variable structural motifs in this family of periplasmic chaperones give important insight into their structure, function, mechanism of action and evolutionary relationship with the immunoglobulin superfamily. J Antimicrob Chemother, 1992 Apr, 29 Suppl A, 13 - 7 Antibacterial activity in vitro of cefpirome against clinical isolates causing sexually transmitted diseases; Limbert M et al.; The in-vitro activity of cefpirome was compared with other antibiotics against organisms causing sexually transmitted diseases (STD) . The excellent activity of cefpirome against Neisseria gonorrhoeae (MIC90 1.0 mg/L), Haemophilus ducreyi (MIC90 0.5 mg/L), and Gardnerella vaginalis (MIC90 1.0 mg/L) suggests that this agent might be useful in the empirical treatment of a variety of venereal diseases. Can Commun Dis Rep, 1992 Mar 27, 18(6), 42 - 7 A survey of invasive Haemophilus influenzae infections--England and Wales; Avidity and bactericidal activity of antibody elicited by different Haemophilus influenzae type b conjugate vaccines . The Vaccine Study Group; Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St Louis, MoOBJECTIVE--Antibody avidity is a measure of the functional affinity of serum antibody to bind to antigen . In this study, we compared the avidity of antibodies elicited by vaccination with three Haemophilus influenzae type b (Hib) conjugate vaccines and investigated the relationship between antibody avidity and the ability of antibody to activate complement-mediated bactericidal activity . DESIGN--A convenience sample of 171 postvaccination serum samples with more than 0.5 microgram/mL of anticapsular antibody, the minimum concentration required for measurement of avidity . The serum samples were obtained from infants participating in immunogenicity trials with Hib capsular polysaccharide (PRP) conjugated to meningococcal outer membrane protein complex (PRP-OMPC) or to tetanus toxoid (PRP-T), or PRP oligomers conjugated to a nontoxic mutant diphtheria toxin, CRM197 (Oligo-CRM) . PATIENTS--Healthy infants recruited in private practices . PRIMARY OUTCOME MEASURES--Avidity of vaccine-induced serum anticapsular antibody and serum bactericidal titers . RESULTS--In infants vaccinated at 2, 4, and 6 months of age, Oligo-CRM evoked antibody of higher avidity than PRP-OMPC (P less than .001) . The mean avidity of antibody elicited by PRP-T was intermediate, being lower than Oligo-CRM (P less than .02) but higher than PRP-OMPC (P = .001) . Also, after one dose, 18-month-old infants given Oligo-CRM had higher avidity antibodies compared with those given PRP-OMPC (P less than .001) . Half of the infants in both age groups who were given Oligo-CRM developed antibody avidity of 2.50 nM-1 or greater, whereas more than two thirds of the infants given PRP-OMPC had avidity values of 1.25 nM-1 or less . Antibodies with avidity of 1.25 nM-1 or less were, on average, 6.6-fold less active in assays of complement-mediated bactericidal activity than antibodies with avidity of 2.50 nM-1 or greater (P less than .001) . CONCLUSIONS--Oligo-CRM and PRP-T conjugate vaccines elicit higher avidity antibody than PRP-OMPC, and high-avidity antibody is more potent than low-avidity antibody in serum bactericidal assays . Consideration should be given to including measurement of antibody avidity in assessment of new vaccines since avidity may affect the ability of serum antibody to confer protection against disease. Anal Biochem, 1992 Mar, 201(2), 343 - 9 Carbohydrate composition analysis of bacterial polysaccharides: optimized acid hydrolysis conditions for HPAEC-PAD analysis; Ip CC et al.; The capsular polysaccharide from Haemophilus influenzae type b (polyribosyl ribitol-phosphate; PRP) and the capsular polysaccharides from Streptococcus pneumoniae types 6B, 14, 18C, and 23F (Pn6B, Pn14, Pn18C, and Pn23F) were subjected to acid hydrolysis using hydrofluoric (HF) and/or trifluoroacetic acid (TFA) and high-pH anion-exchange chromatography with pulsed amperometric detection in an effort to identify optimum hydrolysis conditions for composition analysis of their carbohydrate components . With the exception of PRP, composition analyses of polysaccharides containing a phosphate moiety in the repeating unit structure (Pn6B, Pn18C, and Pn23F) are significantly improved by subjecting the sample to HF hydrolysis (65 degrees C, 1 h) followed by TFA hydrolysis (98 degrees C, 16 h) . This results in essentially quantitative hydrolysis of the phosphodiester bond to the carbohydrate components, which otherwise remained predominantly phosphorylated and poorly accounted for in the analysis . Optimum analysis of PRP was achieved following a 2-h hydrolysis with TFA at 80 degrees C, whereas Pn14 showed optimum results after a 16-h hydrolysis with TFA at 98 degrees C . These analyses also provide information about the relative susceptibility to acid hydrolysis of the various glycosidic and phosphodiester bonds in these polysaccharides, with evidence to suggest that the acid lability of a given bond can be dramatically different from one polysaccharide to another. J Pediatr, 1992 Mar, 120(3), 367 - 70 Immunogenicity of Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine in children with sickle hemoglobinopathy or malignancies, and after systemic Haemophilus influenzae type b infection; Kaplan SL et al.; To determine the immunogenicity of Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine in specific populations at risk, we administered vaccine to children with sickle cell anemia (n = 19; mean age, 18.3 months, malignancies (n = 18; mean age, 43.1 months), or a recent history of systemic H . influenzae type b infection (n = 17; mean age, 11.9 months) . After one dose of polyribosylribitol phosphate-tetanus toxoid conjugate vaccine the geometric mean titers for polyribosylribitol phosphate antibody were 4.8 micrograms/ml (14/19 greater than 1 microgram/ml), 1.4 micrograms/ml (9/18 greater than 1 microgram/ml), and 5.6 micrograms/ml (15/17 greater than 1 microgram/ml) in these three groups, respectively . Children with sickle cell anemia or a recent history of systemic H . influenzae type b infection had polyribosylribitol phosphate antibody levels comparable to those of normal children of similar age after one or two doses of polyribosylribitol phosphate-tetanus toxoid conjugate vaccine . We conclude that this vaccine is immunogenic in children with underlying conditions associated with an increased risk of H . influenzae type b infection. Antimicrob Agents Chemother, 1992 Mar, 36(3), 545 - 7 Duration of rifampin chemoprophylaxis for contacts of patients infected with Haemophilus influenzae type B; Green M et al.; Rifampin is recommended as a prophylactic treatment for intimate contacts of young children who develop invasive infections with Haemophilus influenzae type B (Hib) . A 4-day course of rifampin (20 mg/kg of body weight per day, not to exceed 600 mg as a maximum single daily dose) is 95% effective in eradicating pharyngeal colonization with Hib, thus effectively reducing the risk of both associated patients and recurrent illness in index patients less than 2 years old . This study compares rates of eradication of pharyngeal colonization with Hib for 2- and 4-day courses of rifampin therapy . One hundred sixty-three patients with Hib infection were treated at Children's Hospital of Pittsburgh between January 1986 and December 1988; prophylaxis was recommended for 128 . Participating families were randomized to receive either 2- or 4-day therapy . Throat swabs were obtained from contacts prior to therapy . Repeat cultures were obtained from colonized contacts 2 days after completing rifampin and again on all contacts 7 to 10 days after completing therapy . Of 68 participating families, 34 received 2-day and 34 received 4-day therapy with rifampin . Twenty-two of 24 colonized contacts in the 2-day group and 17 of 18 in the 4-day group had negative cultures for Hib on follow-up . Two-day therapy with rifampin appears to be as effective as 4-day treatment in the eradication of Hib pharyngeal colonization. Antimicrob Agents Chemother, 1992 Mar, 36(3), 521 - 6 Bactericidal titers of loracarbef (LY 163892) in serum and killing rates in volunteers receiving 400 versus 200 milligrams; Van der Auwera P; In a randomized crossover trial, six volunteers received 200- and 400-mg doses of loracarbef (LY 163892), a new oral cephalosporin . Mean +/- standard error of the mean concentrations in serum obtained after 1.5 and 3 h were 13.2 +/- 2.8 and 4.3 +/- 0.7 mg/liter, respectively, after the 400-mg dose and 6.9 +/- 1.0 and 1.7 +/- 0.2 mg/liter, respectively, after the 200-mg dose . Bactericidal reciprocal titers measured against respiratory pathogens in serum suggested that loracarbef would be highly effective against Streptococcus pneumoniae and Streptococcus pyogenes (median titers, 8 to 128 at 1.5 h and less than 2 to 32 at 3 h) and beta-lactamase-negative Haemophilus influenzae (median titers, 4 at 1.5 h and 2 to 4 at 3 h) . Other species (Branhamella catarrhalis, Streptococcus anginosus, Staphylococcus aureus) were associated with lower bactericidal titers . Killing curves performed against 12 strains demonstrated that the bioactivity of loracarbef (measured by the reduction in the area under the control growth curve) was significantly correlated with the concentration/MIC ratio, whereas the initial rate of killing was not, once the concentration was greater than the MIC . Our results suggest that administration of 400 mg of loracarbef every 8 h might be associated with more favorable pharmacodynamic parameters against target bacteria. Clin Ther, 1992 Mar-Apr, 14(2), 254 - 67 Loracarbef (LY163892) versus amoxicillin/clavulanate in bronchopneumonia and lobar pneumonia; Hyslop DL et al.; In a single-blind study, 134 patients with bronchopneumonia or lobar pneumonia were randomly assigned to receive 400 mg of loracarbef twice daily or 500/125 mg of amoxicillin/clavulanate three times daily for 10 to 14 days . Treatment efficacy was evaluated in 38 patients treated with loracarbef and in 39 treated with amoxicillin/clavulanate in whom pre-treatment positive cultures of pathogens susceptibile to the study drugs were isolated . Streptococcus pneumoniae and Haemophilus influenzae were cultured as single pathogens in 40.3% of the evaluable patients . Among the evaluable patients, 100% of the loracarbef group and 92.3% of the amoxicillin/clavulanate group had a favorable clinical response (cure or improvement) . Bacteriologic response was favorable and the pathogen was eliminated or presumed eliminated in 97.4% of the loracarbef-treated patients and in 92.3% of the amoxicillin/clavulanate-treated patients . Treatment was discontinued in one loracarbef-treated patient because Ludwig's angina, unrelated to the study drug, was diagnosed and in five amoxicillin/clavulanate-treated patients because of diarrhea (two patients), rash (two patients), and nausea and vomiting (one patient) . Diarrhea, the most frequently cited adverse event, was reported by 6.1% of the loracarbef-treated patients and 11.8% of the amoxicillin/clavulanate-treated patients . Asthenia was reported by 0% and 8.8% of the loracarbef and amoxicillin/clavulanate patients, respectively . It is concluded that both loracarbef and amoxicillin/clavulanate are safe and effective in the treatment of acute bacterial pneumonia. Clin Ther, 1992 Mar-Apr, 14(2), 214 - 29 Loracarbef (LY163892) versus amoxicillin/clavulanate in the treatment of acute bacterial exacerbations of chronic bronchitis; Zeckel ML et al.; In this single-blind study, 579 patients with chronic bronchitis were randomly assigned to receive 400 mg of loracarbef twice daily or 500/125 mg of amoxicillin/clavulanate thrice daily for seven days . Treatment efficacy was evaluated in 129 of the loracarbef-treated patients and 120 amoxicillin/clavulanate-treated patients in whom pretreatment positive cultures of pathogens susceptible to both antibiotics were isolated . Three organisms predominated in either pure or mixed cultures in 57.0% of the evaluable patients: Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella (Branhamella) catarrhalis; H influenzae was isolated in 25.0% of the patients with single pathogens . Among the evaluable patients, favorable clinical responses (cure or improvement) were noted in 93.8% of the loracarbef-treated patients and in 95.0% of the amoxicillin/clavulanate-treated patients . A favorable bacteriologic response (pathogen eliminated or presumed eliminated) was found in 82.2% of loracarbef-treated patients and 90.0% of amoxicillin/clavulanate-treated patients . Six patients in the loracarbef group and 14 in the amoxicillin/clavulanate group discontinued treatment because of adverse events . The events were judged to be drug related in four loracarbef-treated patients and in 11 amoxicillin/clavulanate-treated patients . The incidence of diarrhea and other gastrointestinal symptoms was significantly more frequent in the amoxicillin/clavulanate group (13.5% and 5.6%) than in the loracarbef group (4.5% and 1.7%), while the incidence of severe headaches was significantly more frequent in the loracarbef than the amoxicillin/clavulanate group (7.2% vs 3.1%) . It is concluded that loracarbef and amoxicillin/clavulanate are safe and effective in the treatment of acute bacterial exacerbations of chronic bronchitis. Clin Ther, 1992 Mar-Apr, 14(2), 166 - 77 Loracarbef (LY163892) versus amoxicillin/clavulanate in the treatment of acute purulent bacterial bronchitis; Dere WH et al.; In this single-blind study, 488 patients with acute bronchitis were randomly assigned to receive 400 mg of loracarbef twice daily or 500/125 mg of amoxicillin/clavulanate three times daily for seven days . Treatment efficacy was evaluated in 98 patients treated with loracarbef and in 99 treated with amoxicillin-clavulanate in whom pretreatment positive cultures of pathogens susceptible to both study drugs were found . Streptococcus pneumoniae, Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, and Klebsiella pneumoniae were isolated in pure or mixed cultures in 64% of the evaluable patients; S pneumoniae was found in 26% . Among the evaluable patients, the rate of favorable clinical responses (cure and improvement) in the loracarbef group (96 of 98 patients; 98.0%) was similar to that in the amoxicillin/clavulanate group (96 of 99 patients; 97.0%); the favorable bacteriologic response rates were also similar (93.7% vs 92.9%, respectively) . Eight patients in the loracarbef group and nine in the amoxicillin/clavulanate group discontinued treatment because of adverse events . The events were presumed to be drug related in five of the loracarbef group and in seven of the amoxicillin/clavulanate group . During therapy, diarrhea was the most frequently reported event in both groups . However, it occurred in only 8.2% of the loracarbef-treated patients compared with 22.5% of the amoxicillin/clavulanate patients (P less than 0.001) . It is concluded that both loracarbef and amoxicillin/clavulanate are safe and effective in the treatment of acute purulent bacterial bronchitis. Br J Obstet Gynaecol, 1992 Mar, 99(3), 190 - 6 Prenatal microbiological risk factors associated with preterm birth; McDonald HM et al.; OBJECTIVE: To study the vaginal flora of pregnant women at 22-28 weeks gestation to determine whether the presence of specific micro-organisms is significantly associated with preterm birth and prelabour rupture of the membranes . DESIGN: A comprehensive descriptive prospective study of the vaginal micro-flora of women between 22-28 weeks gestation comparing those who gave birth preterm (less than 37 weeks) with those who gave birth at term . Microbiological assessment included cultures for aerobic and anaerobic bacteria, yeasts, genital mycoplasmas and Trichomonas vaginalis . Multiple logistic regression analysis was used to account for confounding obstetric and demographic variables . SETTING: The Queen Victoria Hospital, Adelaide, South Australia . SUBJECTS: 135 women who gave birth preterm compared to 651 women who gave birth at term . MAIN OUTCOME MEASURE: Preterm birth and preterm prelabour rupture of membranes (PROM) RESULTS: The prevalence of Gardnerella vaginalis between 22-28 weeks was significantly higher in women who gave birth preterm compared to women who gave birth at term (23% vs 15%; multiple logistic regression odds ratio (OR) 1.8, 95% confidence intervals (CI) 1.01-3.2, P less than 0.05 . Ureaplasma urealyticum was also found in a higher proportion of women who gave birth preterm (49% vs 32% OR 1.7, 95% CI 1.1-2.6, P less than 0.0005) . Preterm PROM occurred in 42% of whom 60% were carriers of U . urealyticum between 22-28 weeks, compared with 32% in the term group (OR 3.2, CI 1.7-6.1, P less than 0.0005) . When women who received antibiotics between the midtrimester swab and labour were excluded, G . vaginalis was also significantly associated with preterm PROM (OR 2.7, CI 1.1-6.5, P less than 0.05) . The presence of vaginal enteropharyngeal bacteria (E . coli, Klebsiella spp., Haemophilus spp., Staph . aureus) in the midtrimester was not predictive of preterm birth, but when these organisms were found in labour, they appeared to have been acquired later in the pregnancy . CONCLUSION: Women carrying G . vaginalis or U . urealyticum during the midtrimester had nearly twice the risk of preterm birth, while women positive for U . urealyticum had more than a threefold risk of preterm PROM. J Gen Microbiol, 1992 Mar, 138 ( Pt 3), 517 - 22 Copper-zinc superoxide dismutase in Haemophilus species; Langford PR et al.; Copper-zinc superoxide dismutases ({Cu,Zn}-SODs) are ubiquitous in eukaryotes but have rarely been found in prokaryotes . A gene for {Cu,Zn}-SOD (sodC) has recently been cloned from Haemophilus influenzae type b and H . parainfluenzae, so other Haemophilus and related species were screened for the presence of {Cu,Zn}-SODs by visualization of bands of SOD activity in non-denaturing polyacrylamide gels and by gene probing . Strains of H . aphrophilus, H . paraphrophilus, H . haemolyticus, H . paraphrohaemolyticus, some non-typable H . influenzae, H . haemoglobinophilus (canis) and H . parasuis were all found to have {Cu,Zn}-SOD activity (inhibited by 2 mM-cyanide) in polyacrylamide gels . In a Southern blot analysis, DNA from H . aphrophilus, H . paraphrophilus, H . haemolyticus and {Cu,Zn}-SOD-containing non-typable H . influenzae--but not the other species--hybridized to a 360 nucleotide DNA probe containing the 5'-part of sodC cloned from H . influenzae type b . Bacterial {Cu,Zn}-SODs are more prevalent than has previously been recognized. J Rheumatol, 1992 Mar, 19(3), 491 - 3 Early diagnosis of vertebral osteomyelitis due to a rare pathogen: Haemophilus parainfluenzae; Beauvais C et al.; Bone and joint infections due to Haemophilus parainfluenzae are unusual . We describe a case of hematogenous vertebral osteomyelitis caused by this commensal microorganism of nose and oropharynx . Early diagnosis and therapy were possible within a week using sensitive radiologic methods: technetium bone scanning, computed tomography and magnetic resonance imaging. Infect Dis Clin North Am, 1992 Mar, 6(1), 197 - 214 New aspects of prevention and therapy of meningitis; Kaplan SL; Cefotaxime and ceftriaxone are currently the agents of first choice for empiric treatment of bacterial meningitis in children . Further studies are necessary to determine the optimal antibiotic therapy for meningitis caused by Streptococcus pneumoniae isolates relatively or fully resistant to penicillin . The Haemophilus influenzae type b capsular polysaccharide-protein conjugate vaccines undoubtedly will alter the relative importance of the three common meningeal pathogens in pediatrics and make additional studies of the adjunctive use of dexamethasone in the treatment of bacterial meningitis even more critical. Infect Dis Clin North Am, 1992 Mar, 6(1), 177 - 95 Antibiotic resistance in pediatric pathogens; Smith AL; The prevalence of antibiotic resistance is increasing in pediatric pathogens . Methicillin resistance in Staphylococcus aureus and in S . epidermidis, and erythromycin resistance in group A streptococci are becoming major problems . Fortunately, all three species remain susceptible to vancomycin . In certain parts of the world, Haemophilus influenzae b that are resistant to a number of antibiotics are being recognized . Antibiotic therapy of pediatric infections in the future will continue to rely on yet-to-be developed agents. Gesundheitswesen, 1992 Mar, 54(3), 135 - 8 {Chemoprophylaxis in indirectly related cases of Haemophilus influenzae meningitis}; Oertel PJ et al.; In January 1991, in a community near the South German town of Tubingen, an infant and a toddler developed a Haemophilus influenzae type B (HIB) meningitis within a period of one week . The patients had no direct contact with each other, but each of them had a healthy sibling that was older . These siblings attended the same kindergarten and the same group . Five months later we noted the same situation in another community . Two infants fell ill with HIB meningitis at short intervals from each other, and again both patients had no common contacts, but they did have healthy siblings attending the same kindergarten and group . Hence, it must be assumed that the HIB strain circulated among the healthy kindergarten children and was transmitted by these to the patients . In order to prevent that after the two pairs of patients we had observed, further patients would follow among the kindergarten children or their younger siblings, chemoprophylaxis with rifampicin was initiated in all kindergarten children, their younger siblings and the adult Kindergarten staff . The problems arising from these unusual case constellations in respect of mass prophylaxis with rifampicin in cases of Haemophilus influenzae type B meningitis that are merely indirectly linked to each other, are discussed. Clin Infect Dis, 1992 Mar, 14(3), 633 - 8 Bite wounds and infection; Goldstein EJ; One of every two Americans will be bitten by an animal or by another person at some point . Bites account for approximately 1% of all visits to emergency rooms; injuries inflicted by dogs are most common . The bacteria involved in infection of bite wounds include Pasteurella multocida, Staphylococcus aureus, Staphylococcus intermedius, alpha-hemolytic streptococci, Capnocytophaga canimorsus, and other members of the oral flora . Anaerobic bacteria are present in approximately one-third of bite wounds and are associated with the formation of abscesses and with relatively serious infections . P . multocida is found in infections of cat bites more than 50% of the time . The bacteriology of bite wounds inflicted by exotic animals reflects the animals' oral flora . Bites inflicted by humans are often more serious than those inflicted by animals . Infections of human bites are associated with alpha-hemolytic streptococci, S . aureus, Eikenella corrodens, Haemophilus species, and (in more than 50% of cases) anaerobic bacteria . The principles of management of bite wounds are discussed. J Bacteriol, 1992 Mar, 174(6), 2002 - 13 Phylogeny of 54 representative strains of species in the family Pasteurellaceae as determined by comparison of 16S rRNA sequences; Dewhirst FE et al.; Virtually complete 16S rRNA sequences were determined for 54 representative strains of species in the family Pasteurellaceae . Of these strains, 15 were Pasteurella, 16 were Actinobacillus, and 23 were Haemophilus . A phylogenetic tree was constructed based on sequence similarity, using the Neighbor-Joining method . Fifty-three of the strains fell within four large clusters . The first cluster included the type strains of Haemophilus influenzae, H . aegyptius, H . aphrophilus, H . haemolyticus, H . paraphrophilus, H . segnis, and Actinobacillus actinomycetemcomitans . This cluster also contained A . actinomycetemcomitans FDC Y4, ATCC 29522, ATCC 29523, and ATCC 29524 and H . aphrophilus NCTC 7901 . The second cluster included the type strains of A . seminis and Pasteurella aerogenes and H . somnus OVCG 43826 . The third cluster was composed of the type strains of Pasteurella multocida, P . anatis, P . avium, P . canis, P . dagmatis, P . gallinarum, P . langaa, P . stomatis, P . volantium, H . haemoglobinophilus, H . parasuis, H . paracuniculus, H . paragallinarum, and A . capsulatus . This cluster also contained Pasteurella species A CCUG 18782, Pasteurella species B CCUG 19974, Haemophilus taxon C CAPM 5111, H . parasuis type 5 Nagasaki, P . volantium (H . parainfluenzae) NCTC 4101, and P . trehalosi NCTC 10624 . The fourth cluster included the type strains of Actinobacillus lignieresii, A . equuli, A . pleuropneumoniae, A . suis, A . ureae, H . parahaemolyticus, H . parainfluenzae, H . paraphrohaemolyticus, H . ducreyi, and P . haemolytica . This cluster also contained Actinobacillus species strain CCUG 19799 (Bisgaard taxon 11), A . suis ATCC 15557, H . ducreyi ATCC 27722 and HD 35000, Haemophilus minor group strain 202, and H . parainfluenzae ATCC 29242 . The type strain of P . pneumotropica branched alone to form a fifth group . The branching of the Pasteurellaceae family tree was quite complex . The four major clusters contained multiple subclusters . The clusters contained both rapidly and slowly evolving strains (indicated by differing numbers of base changes incorporated into the 16S rRNA sequence relative to outgroup organisms) . While the results presented a clear picture of the phylogenetic relationships, the complexity of the branching will make division of the family into genera a difficult and somewhat subjective task . We do not suggest any taxonomic changes at this time. Am J Hematol, 1992 Mar, 39(3), 176 - 82 Polysaccharide encapsulated bacterial infection in sickle cell anemia: a thirty year epidemiologic experience; Wong WY et al.; Annual age-specific incidence rates of Streptococcus pneumoniae or Haemophilus influenzae bacterial septicemia in sickle cell anemia (SS) were determined for the years of 1957 through 1989 . Forty-nine patients had 64 episodes of septicemia among a population of 786 SS patients observed for 8,138 person-years . Peak frequency of infection occurred between 1968-1971 and 1975-1981 with a conspicuous absence of episodes in 1972, 1973, 1982-1984, and 1986-1987, thus demonstrating cycles of high and low attack rates . The annual age-specific incidence rate of septicemia varied from 64.5 (1965) to 421.1 (1980) per 1,000 person-years for those under 2 years of age and never exceeded 10.2 per 1,000 in those over 4 years of age . Following the introduction of pneumococcal polyvalent vaccine in 1978, incidence of infection decreased in SS children greater than 2 years of age . No modification of the risk of infection was observed in immunized children less than 2 years of age . During these three decades, there has been a ten-fold increase in the number of SS adults over 20 years of age . The relative risk of chronic sickle complications comparing the survivors of septicemia to the non-infected patients was: subsequent death 1.76, retinopathy 4.06, avascular necrosis 1.95, symptomatic cholelithiasis 1.33, stroke 1.30, and priapism 1.26 . These data suggest that prognosis for lifetime severe SS is initially manifested as an increased risk of septicemia during childhood. Clin Exp Immunol, 1992 Mar, 87(3), 404 - 9 An association between homozygous C3 deficiency and low levels of anti-pneumococcal capsular polysaccharide antibodies; Hazlewood MA et al.; Inherited deficiencies of complement components are associated with an increased risk of infection by encapsulated, high grade bacterial pathogens such as Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria meningitidis . Hence, the levels of antibodies to bacterial capsular polysaccharide antigens were measured using ELISA in 65 patients with inherited deficiencies covering the classical, alternative and terminal components of the complement cascade . Three of the four C3-deficient individuals studied were found to be almost totally deficient in specific anti-pneumococcal capsular polysaccharide (PCP) antibodies . These individuals had a history of recurrent pneumococcal sepsis . While single individuals with C1r, C2 and C1Inh deficiency were found to have low anti-PCP antibody levels, no other group of complement deficiency had significantly reduced anti-PCP antibody levels compared with 100 controls . Antibody levels to the other two polysaccharides were not significantly lower in the patient groups . These findings suggest that C3 may be able to provide a stimulatory signal to promote the production of anti-PCP antibodies. Am J Dis Child, 1992 Mar, 146(3), 340 - 2 Immunogenicity of Haemophilus influenzae type b conjugate vaccine in children with sickle cell disease; Rubin LG et al.; OBJECTIVE--To determine the safety and immunogenicity of Haemophilus influenzae type b conjugate vaccine in children with sickle cell disease . RESEARCH DESIGN--Prospective, nonrandomized, nonblinded study . SETTING--Hospital-based, comprehensive sickle cell center . PATIENTS--Children with sickle cell disease aged 18 months to 18 years who were previously unvaccinated or had an inadequate or waning response to H influenzae type b polysaccharide vaccine . SELECTION PROCEDURES--Consecutive eligible patients . INTERVENTIONS--Vaccination and observation for adverse effects . Blood samples were taken before and 1 to 2 and 6 months after vaccination to measure anticapsular antibody levels . MEASUREMENTS AND RESULTS--Vaccination was well tolerated . One hundred percent and 96% of the 31 immunized children had postvaccination anticapsular antibody concentrations of greater than 0.15 and 1.0 mg/L, respectively . Six months after vaccination, 100% and 89% of children had these antibody concentrations . CONCLUSIONS--H influenzae type b conjugate vaccines are safe and highly immunogenic in children with sickle cell disease . It is likely that these vaccines will be protective against invasive H influenzae type b disease. Proc Natl Acad Sci U S A, 1992 Mar 1, 89(5), 1973 - 7 Identification of a genetic locus of Haemophilus influenzae type b necessary for the binding and utilization of heme bound to human hemopexin; Hanson MS et al.; The mechanism(s) used by Haemophilus influenzae to acquire the essential nutrient heme from its human host has not been elucidated . The heme carried by the high-affinity serum protein hemopexin is one potential source of this micronutrient in vivo . A colony-blot assay revealed that heme-human hemopexin-binding activity was shared among most capsular serotype b strains of H . influenzae but was uncommon among other strains . We have identified a recombinant clone binding heme-human hemopexin from a H . influenzae type b (Hib) genomic library expressed in Escherichia coli . Both the Hib strain and the heme-hemopexin-binding clone expressed a polypeptide of approximately 100 kDa that bound radiolabeled heme-hemopexin . Oligonucleotide linker insertion mutagenesis of the plasmid DNA from this recombinant clone was used to confirm that expression of the 100-kDa protein correlated with the heme-hemopexin-binding activity . Exchange of one of these mutant alleles into the Hib chromosome eliminated expression of both the 100-kDa protein and the heme-hemopexin-binding activity . Furthermore, this Hib mutant was unable to utilize heme-human hemopexin as a heme source. Proc Natl Acad Sci U S A, 1992 Mar 1, 89(5), 1626 - 30 The gene encoding cAMP receptor protein is required for competence development in Haemophilus influenzae Rd; Chandler MS; The Haemophilus influenzae Rd strain JG87 contains a single mini-Tn10kan insertion that causes a deficiency in the development of competence for genetic transformation . The DNA fragment containing this insertion mutation, as well as the wild-type locus, was cloned, mapped, and sequenced . The sequence contained an open reading frame for a protein of 224 amino acids with a predicted Mr of 25,152 . The deduced protein sequence showed strong similarity to the Escherichia coli cAMP receptor protein . The E . coli crp gene cloned on a multicopy plasmid was shown to fully complement the competence-deficient phenotype of the mutant strain; thus, the H . influenzae gene was named crp . These results suggest that H . influenzae cAMP-cAMP receptor protein complex functions to regulate one or more promoters essential for the development of competence in H . influenzae Rd . Features of a gene upstream of H . influenzae crp that is homologous to the E . coli ttk gene are also described. J Clin Invest, 1992 Mar, 89(3), 729 - 38 Immunoglobulin light chain variable region gene sequences for human antibodies to Haemophilus influenzae type b capsular polysaccharide are dominated by a limited number of V kappa and V lambda segments and VJ combinations; Adderson EE et al.; The immune repertoire to Haemophilus influenzae type b capsular polysaccharide (Hib PS) appears to be dominated by certain light chain variable region genes (IgVL) . In order to examine the molecular basis underlying light chain bias, IgVL genes