Haemophilus

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 have been cloned from a panel of heterohybridomas secreting human anti-Hib PS (antibody) (anti-Hib PS Ab) . One hybridoma, representative of the predominant serum clonotype of anti-Hib PS Ab in older children and adults following immunization or Hib infection, uses a V kappa II segment identical to the germline gene A2, and a JK3 segment . A second kappa hybridoma uses a member of the V kappa I family and a JK4 segment . Four lambda antibodies, all cross-reactive with the structurally related antigen Escherichia coli K100 PS, use V lambda VII segments which are 96-98% homologous to one another, and may originate from a single germline gene . Two additional lambda antibodies, not K100-cross-reactive, are encoded by members of the V lambda II family . All lambda antibodies use highly homologous J lambda 2 or J lambda 3 segments . The VJ joints of all lambda antibodies and the V kappa II-encoded antibody are notable for the presence of an arginine codon, suggesting an important role in antigen binding . Although more complex than heavy chain variable region gene usage, a significant portion of serum anti-Hib PS Ab is likely to be encoded by a limited number of V kappa and V lambda segments and VJ combinations, which may be selectively expressed during development, or following antigen exposure.

Infect Immun, 1992 Mar, 60(3), 826 - 31
Molecular cloning, nucleotide sequence, and characterization of a 40,000-molecular-weight lipoprotein of Haemophilus somnus; Theisen M et al.; A gene of Haemophilus somnus encoding the major 40,000-molecular-weight antigen (LppA) was cloned on a 2-kb Sau3AI fragment . The nucleotide sequence of the entire DNA insert was determined . One open reading frame, encoding a 247-residue polypeptide with a calculated molecular weight of 27,072, was identified . This reading frame was confirmed by sequencing the fusion joint of two independent IppA::TnphoA gene fusions . The 21 amino-terminal amino acids of the deduced polypeptide showed strong sequence homology to the signal peptide of secreted proteins, and the sequence Leu-Leu-Ala-Ala-Cys at the putative cleavage site is identical to the consensus cleavage sequence of lipoproteins from gram-negative bacteria . The presence of the lipid moiety on the protein was shown by incorporation of radioactive palmitic acid into the natural H . somnus protein . Palmitic acid could also be incorporated into the recombinant protein in Escherichia coli . Synthesis of the mature LppA lipoprotein was inhibited by globomycin, showing that cleavage of the signal peptide is mediated by signal peptidase II in both organisms . By using site-directed mutagenesis, the cysteine residue at the cleavage site was changed to glycine . Radiolabelled palmitate was not incorporated into the mutated protein, showing that lipid modification occurs at the Cys-22 residue.

Infect Immun, 1992 Mar, 60(3), 810 - 6
Isolation of an outer membrane hemin-binding protein of Haemophilus influenzae type b; Lee BC; Haemophilus influenzae is a heme-dependent bacterium . However, little is known of the heme-iron uptake mechanism in this organism . By using a batch ligand affinity chromatography method, a hemin-binding protein of 39,500 molecular weight was isolated from total membranes derived from H . influenzae type b grown under iron-depleted but not under iron-sufficient conditions . Detection of the hemin-binding protein in a whole-cell binding assay demonstrated a surface-exposed location . Competition binding experiments indicated that this hemin-protein interaction was specific, since only hemin or heme-containing proteins, such as human hemoglobin and bovine catalase, but not protoporphyrin IX, iron-loaded human lactoferrin, or transferrin, could abrogate binding . In a limited survey of other H . influenzae strains, an identical hemin-binding protein was isolated, implying that this polypeptide may be structurally and functionally conserved among strains.

Infect Immun, 1992 Mar, 60(3), 1156 - 62
Haemophilus ducreyi, a cytotoxin-producing bacterium; Purven M et al.; An extra- and an intracellular product from the bacterium Haemophilus ducreyi were shown to have a cytotoxic effect on cell lines of epithelial origin, e.g., HEp-2 and HeLa cells . The cytotoxic effect appeared on cells within 24 h and resulted in cell death and morphologically changed cells . The cytotoxic activity was heat and pronase sensitive . The activity could be removed by incubation with the target cells, suggesting attachment of the agent to the cells . The cytotoxic products were secreted into the environment during exponential growth of bacteria and produced by most of the H . ducreyi strains tested . The activity was neutralized by homologous rabbit immune serum but not by the corresponding preimmune serum . The results indicate that strains of H . ducreyi produce a cytotoxin which may be of importance to the pathogenesis of chancroid.

Jpn J Antibiot, 1992 Mar, 45(3), 318 - 28
{Bacteriological and clinical studies of panipenem/betamipron in pediatrics}; Akita H et al.; We carried out bacteriological and clinical studies of panipenem/betamipron (PAPM/BP), a newly-developed carbapenem antibiotic, in pediatrics, and the following results were obtained: 1 . When antibacterial activities of panipenem (PAPM) were determined, it was found that MICs against such Gram-positive cocci as Staphylococcus aureus and Streptococcus pneumoniae and against such Gram-negative rods as Escherichia coli, Haemophilus influenzae, Pseudomonas aeruginosa, and Branhamella catarrhalis were all sufficiently low . 2 . PAPM showed better MIC-correlated antibacterial activities against 215 subcultured strains of methicillin-resistant S . aureus (MRSA) than imipenem . 3 . Clinical efficacies were evaluated to be excellent in 23 of 34 patients treated with PAPM/BP, excluding 3 patients from the efficacy evaluation . In addition, good responses were obtained in 10 patients but poor response in one, showing the overall efficacy rate of 97.1% . As for bacteriological efficacies, the eradication rate was also determined to be high, 92.6% . 4 . As for side effects, rash appeared in 2 patients, and soft stool and diarrhea occurred in one each . The overall incidence of side effects was calculated to be 10.8% . As for abnormal laboratory findings, increases of eosinophiles in 4 patients, thrombocytes in 2, total bilirubin in 1, and GOT in 1 were observed . From these results, PAPM/BP was thought to be a highly useful drug in pediatrics.

Mol Microbiol, 1992 Mar, 6(5), 665 - 76
Monoclonal antibodies specific to porin of Haemophilus influenzae type b: localization of their cognate epitopes and tests of their biological activities; Srikumar R et al.; The major outer membrane protein of Haemophilus influenzae type b (Hib) is porin (Mr 38,000, 341 amino acids) . To identify antigenic determinants on Hib porin that might be exposed at the bacterial cell surface, seven mouse monoclonal anti-Hib porin antibodies were generated . The monoclonal antibodies were tested for their binding to intact cells by flow cytometry; all but one bound to the cell surface . Digestions of Hib porin with cyanogen bromide, hydroxylamine or trypsin generated fragments, the identities of which were confirmed by microsequencing of the amino termini . Following electrophoresis and immunoblotting of the fragments, the specificities of the monoclonal antibodies for their cognate sequences were determined . The porin gene ompP2 was expressed in the baculovirus expression vector system; the recombinant porin was recognized by all of the monoclonal antibodies . Deletions were created by omega mutagenesis of ompP2, generating proteins truncated after amino acids 139, 174, 182, and 264 . These deletion proteins were tested for reactivities with the monoclonal antibodies, thereby establishing the boundaries of three antigenic determinants that were recognized by the monoclonals: domain (i), amino acids 104-139; domain (ii) amino acids 162-174; and domain (iii), amino acids 267-341 . The biological activities of monoclonal antibodies that were representative of these three classes were tested for their bactericidal activity in complement-mediated lysis of whole cells . The monoclonal antibodies were also tested for their immunoprotective properties in the infant rat model of bacteraemia . Although the monoclonal antibodies were surface-binding, they were neither bactericidal nor protective.

J Infect Dis, 1992 Mar, 165(3), 464 - 70
Effect of pili-specific antibodies on the adherence of Haemophilus influenzae type b to human buccal cells; Forney LJ et al.; Different strains of Haemophilus influenzae type b (Hib) produce antigenically distinct pili that mediate adherence to human buccal epithelial cells . This study determined the ability of antibodies specific for the LKP3 pili of Haemophilus influenzae type b to inhibit the adherence of Hib strain Eagan (p+) . Antiserum was prepared by immunization of rabbits with pili purified from Hib strain Eagan (p+) . The presence of pili-specific antibodies in the immune serum was shown by selective immunoprecipitation of pilin and by electron microscopy of cells labeled with immunogold . Immune serum, affinity-purified antibody, and Fab fragments from immune serum significantly inhibited (P less than .001) adherence of strain Eagan (p+) to human buccal epithelial cells whereas preincubation with preimmune rabbit serum or Fab fragments from preimmune serum had no significant effect on adherence . Dilution of the immune serum, affinity-purified antibodies, or Fab fragments from immune serum resulted in decreased inhibition of Hib adherence . These results indicate that antibodies specific for LKP3 pili can effectively inhibit adherence of Hib strain Eagan (p+) and probably other strains that express this pilus serotype.

J Gen Microbiol, 1992 Mar, 138 ( Pt 3), 509 - 15
Tn916 insertion mutagenesis in Escherichia coli and Haemophilus influenzae type b following conjugative transfer; Holland J et al.; Transposon Tn916 was shown to be capable of direct conjugative transfer in broth and membrane matings between strains of Escherichia coli K12 and between E . coli K12 and Haemophilus influenzae type b . Only Tn916 was transferred, but Tn916 donor ability was not itself inheritable by the recipients and seemed to be associated with the presence of Tn916 on a non-conjugative pBR322-derived vector in the original donor strain . Transfer of Tn916 by conjugation was found to be an efficient method for producing insertion mutations in the chromosome of recipient cells . Although such insertions were unstable when the cells were grown under non-selective conditions, it was possible to show that over 40% of the isolated Tn916 insertions in the chromosome of E . coli K12 were in gene(s) concerned with histidine biosynthesis, implying that there is a partial hot-spot for Tn916 insertion on the E . coli K12 chromosome . When a strain of H . influenzae type b was used as a recipient, out of approximately 1500 transconjugants tested, two mutants were isolated with insertions in genes controlling the expression of iron-regulated transferrin-binding proteins . These mutants constitutively produced major 76 kDa and minor 90 kDa proteins which bound transferrin, even when grown under iron-sufficient conditions . Tn916 insertion mutagenesis, following transfer by conjugation, is a convenient method for isolating mutations in genes concerned with iron acquisition by this important human pathogen.

J Clin Microbiol, 1992 Mar, 30(3), 744 - 5
Disk diffusion quality control guidelines for Haemophilus susceptibility tests using cefdinir, CI-960, fleroxacin, temafloxacin, and trospectomycin; Bale MJ et al.; A multilaboratory study to determine disk diffusion quality control ranges for Haemophilus influenzae ATCC 49247 and five investigational drugs was performed . Multiple lots of Haemophilus Test Medium and antibiotic disks were used for replicate testing in conformance with the recommendations of the National Committee for Clinical Laboratory Standards . Quality control disk zone diameter ranges were proposed for cefdinir, CI-960, fleroxacin, temafloxacin, and trospectomycin.

Nucleic Acids Res, 1992 Feb 25, 20(4), 705 - 9
Cloning and expression of the HpaI restriction-modification genes; Ito H et al.; The genes from Haemophilus parainfluenzae encoding the HpaI restriction-modification system were cloned and expressed in Escherichia coli . From the DNA sequence, we predicted the HpaI endonuclease (R.HpaI) to have 254 amino acid residues (Mr 29,630) and the HpaI methyltransferase (M.HpaI) to have 314 amino acid residues (37,390) . The R.HpaI and M.HpaI genes overlapped by 16 base pairs on the chromosomal DNA . The genes had the same orientation . The clone, named E . coli HB101-HPA2, overproduced R.HpaI . R.HpaI activity from the clone was 100-fold that from H . parainfluenzae . The amino acid sequence of M.HpaI was compared with those of other type II methyltransferases.

Med Klin (Munich), 1992 Feb 15, 87(2), 58 - 62
{Evaluation of the so-called basic cephalosporins using the serum bactericidal test}; Milatovic D et al.; The serum bactericidal activity (SBA) was studied one hour and four hours after intravenous administration of 1 g and 2 g cefotiam, 1.5 g cefuroxime and 2 g cefazolin to six volunteers . The 136 clinical isolates tested included Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Haemophilus influenzae . One hour after administration no significant differences in the activity against staphylococci were noted in the antibiotics tested . Four hours after administration of cefazolin 96% of the Staphylococcus aureus strains were killed at a serum dilution of 1:8, whereas only one strain was killed by cefuroxime and none by cefotiam under the same conditions . The highest SBA-titers against Haemophilus influenzae were achieved with cefotiam at a dosage of 2 g . SBA-titers against Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were higher after administration of 1 g cefotiam than after administration of 1.5 g cefuroxime and 2 g cefazolin, respectively.

JAMA, 1992 Feb 5, 267(5), 673 - 8
Impact of Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine on responses to concurrently administered diphtheria-tetanus-pertussis vaccine; Clemens JD et al.; OBJECTIVE--To assess whether serum antibody responses to diphtheria-tetanus-pertussis (DTP) vaccine were affected by coadministration of Haemophilus influenzae type b capsular polyribosylribitol phosphate polysaccharide-tetanus protein (PRP-T) conjugate vaccine when given to patients at 2, 4, and 6 months of age . DESIGN--Randomized, double-blind clinical trial . SETTING--Urban Santiago, Chile . PATIENTS--Healthy infants assembled from health centers . Two hundred seventy-eight (74%) of 375 eligible infants participated; 222, who complied with the complete protocol, constituted the primary group under analysis . INTERVENTIONS--One of three vaccine regimens was given to study participants at 2, 4, and 6 months of age, either DTP mixed in the same syringe as PRP-T (group 1); DTP and PRP-T given at separate injection sites (group 2); or DTP without PRP-T (group 3) . PRIMARY OUTCOME MEASURES--Titers of serum antidiphtheria toxoid, antitetanus toxoid, and pertussis agglutinin antibodies were measured in blood samples taken from patients 2 months after each dose . RESULTS--Serum antidiphtheria toxoid and antitetanus toxoid responses showed no important depressions in the patients receiving PRP-T . In contrast, geometric mean titers (GMTs) of pertussis agglutinins, expressed as reciprocal serum dilutions, after both the second and third doses (GMT2, GMT3) were lowest in group 1 (GMT2 = 89; GMT3 = 1230), intermediate in group 2 (GMT2 = 123; GMT3 = 1995), and highest in group 3 (GMT2 = 210; GMT3 = 3090; P less than .05 for trend group 1 less than group 2 less than group 3 after each dose) . Antipertussis toxin and antipertussis filamentous hemagglutinin antibody titers also were depressed in patients who received PRP-T . Follow-up of a subset at 18 months revealed an expected decline of pertussis agglutinin titers to near baseline levels in each group . CONCLUSIONS--Concurrent administration of PRP-T vaccine with DTP vaccine, either in the same syringe or at different sites, interfered with antipertussis responses to a primary series of immunizations . Although the clinical significance of this antagonism is uncertain, these data underscore the caution required in decisions to add new vaccines to existing immunization regimens.

Am Fam Physician, 1992 Feb, 45(2), 693 - 7
Treatment of exacerbations of COPD; Rosen MJ; Chronic obstructive pulmonary disease (COPD) affects approximately 14 million Americans . Treatment of COPD includes bronchodilators, corticosteroids and antibiotics . The most common bacterial isolates during exacerbations of COPD are Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis.

J Pediatr, 1992 Feb, 120(2 Pt 1), 184 - 9
Comparative trial in infants of four conjugate Haemophilus influenzae type b vaccines; Decker MD et al.; We performed a double-blind, randomized trial to compare the immunogenicity and reactogenicity of four conjugate Haemophilus influenzae type b vaccines given to infants 2, 4, and 6 months of age . Adverse reactions attributable to the vaccines were few and minor . The rates of systemic reactions did not differ among the various vaccines and were similar to those seen among children receiving conventional diphtheria-tetanus-pertussis vaccine . However, the four conjugate H . influenzae type b vaccines differed markedly in ability to stimulate antibody production . Mean antibody levels after three injections of polyribosylribitol phosphate conjugated with mutant diphtheria protein (PRP-CRM) or polyribosylribitol phosphate conjugated with tetanus toxoid (PRP-T) were 3.08 micrograms/ml and 3.64 micrograms/ml, respectively, significantly higher than those after the use of polyribosylribitol phosphate conjugated with outer-membrane protein of Neisseria meningitidis (PRP-OMP) (1.14 micrograms/ml) or polyribosylribitol phosphate conjugated with diphtheria toxoid (PRP-D) (0.28 microgram/ml) . Only PRP-OMP produced a clinically pertinent elevation in antibody level after two injections (0.84 microgram/ml); the third injection of PRP-OMP produced a modest but statistically significant further elevation in mean antibody level (1.14 micrograms/ml) . Only 29% of infants receiving PRP-D had antibody levels of 1 micrograms/ml, compared with 55%, 75%, and 83% of those receiving PRP-OMP, PRP-CRM, and PRP-T, respectively . We conclude that all four vaccines are safe and that all but PRP-D appear appropriate for use in a primary immunization series during infancy . The unique serologic response to PRP-OMP offers both advantages and disadvantages in comparison with PRP-CRM and PRP-T.

J Bacteriol, 1992 Feb, 174(3), 1029 - 35
A lipoprotein of Yersinia enterocolitica facilitates ferrioxamine uptake in Escherichia coli; Baumler AJ et al.; A cloned fragment of Yersinia enterocolitica DNA complemented the defect in ferrioxamine B uptake of an Escherichia coli fhuE mutant lacking the outer membrane high-affinity transport protein FhuE . Subcloning revealed that a 13.7-kDa outer membrane protein was required for complementation . The amino acid sequence deduced from the nucleotide sequence showed extensive homology to PCPHi, an outer membrane lipoprotein of Haemophilus influenzae . We therefore termed this protein PCPYe . Plasmid-encoded pcpY mediated a low-affinity uptake of ferrioxamine B which may be caused by changes in the permeability of the outer membrane due to an overexpression of this outer membrane protein . A transposon insertion mutant in the plasmid-encoded pcpY gene was transferred into the chromosome of Y . enterocolitica . The resulting mutation had no effect on the high-affinity uptake of ferrioxamine B in Yersinia cells . Using the antibiotic ferrimycin we were able to isolate a Y . enterocolitica mutant lacking the high-affinity outer membrane receptor for ferrioxamine uptake, termed FoxA.

Infect Immun, 1992 Feb, 60(2), 687 - 9
Clustering of an outer membrane adhesin of Haemophilus parainfluenzae; Liljemark WF et al.; Haemophilus parainfluenzae synthesizes an outer membrane protein adhesin which mediates binding to oral streptococci, salivary pellicle, and neuraminidase-treated erythrocytes . An indirect gold labeling technique and immunoelectron microscopy verified the location of this outer membrane protein . Further, a clustering of gold particles was observed in irregular patches at the cell surface.

Infect Immun, 1992 Feb, 60(2), 590 - 5
Antigenic diversity in Haemophilus ducreyi as shown by western blot (immunoblot) analysis; Roggen EL et al.; The antigenic diversity within a panel of 63 Haemophilus ducreyi isolates was examined by Western blot (immunoblot) analysis with a pool of 238 well-characterized human antisera . When a serum pool adsorbed on a mixture of Haemophilus influenzae, H . parainfluenzae, and H . parahaemolyticus was used, the immunoprofiles suggested that prominent antigenic proteins involved in the human immune response have apparent molecular masses of 63, 42, 34 to 30, and 28.5 to 28 kDa . Preliminary subcellular localization revealed that these antigens are associated with the cellular membrane . Two subsets of antigens were discriminated by detergent extraction . There was no evidence that the antigen composition is altered by changing the growth conditions . With a serum pool adsorbed on the Haemophilus spp . mixture supplemented with Actinobacillus actinomycetemcomitans, Pasteurella ureae, Neisseria gonorrhoeae, and Escherichia coli, antigenic determinants more specific for H . ducreyi were identified . An immunodominant 28.5- to 28-kDa protein was expressed by all H . ducreyi isolates . In the range from 34 to 30 kDa, 56 isolates revealed a dominant protein with variable molecular mass . By using both proteins (28.5 to 28 kDa and 34 to 30 kDa) as immunotypic markers, seven different immunopatterns were identified . Antigenic diversity among isolates from different geographical origins as well as from a single area was observed.

Enferm Infecc Microbiol Clin, 1992 Feb, 10(2), 79 - 88
{Meningitis in pediatrics . Clinical and epidemiological study of 173 cases}; Roca J et al.; BACKGROUND: To know the incidence, clinical presentation, differential diagnosis and resistance level to antibiotics in pediatric meningitis . METHODS: 173 cases of meningitis (bacterial: 69, viral: 104) have been prospectively followed during 1988 according to a previously established clinical and laboratory protocol . RESULTS: Meningitis attack rate was 60 cases/100,000 children younger than 15 years per year (meningococcal: 25/100,000, Haemophilus: 2/100,000) . Mortality was 1.4% . 40% of bacterial meningitis received previous antibiotic treatment . Sensitivity of culture, Gram stain, and direct antigen detection by latex and EIA was 79%, 61.7%, 20.5% and 34%, respectively . Bacterial and viral differential diagnosis, by the application of Boyer's score was 95% sensitive and 98% specific . Four out of six cases of Haemophilus meningitis were ampicillin and chloramphenicol resistant; 39% of meningococcus had their penicillin susceptibility decreased between 2 and 8 times, although no therapeutic failures were seen . CONCLUSIONS: Laboratory parameters might not separate bacterial and viral meningitis at early stages of illness . Gram stain is an excellent and sensitive method of bacterial detection in CSF . Moderate resistance to penicillin in meningococcus is very frequent but clinical failures are not yet present.

Jpn J Antibiot, 1992 Feb, 45(2), 143 - 54
{A study on in vitro antibacterial activity and clinical usefulness in respiratory tract infections of panipenem/betamipron, a newly synthesized carbapenem antibiotic}; Shishido H et al.; Panipenem/betamipron (PAPM/BP) is a combination drug of PAPM, a new parenteral carbapenem antibiotic and BP, an amino acid derivative at a weight ratio of 1:1 . Its in vitro antibacterial activities against clinically isolated respiratory pathogenic bacteria were determined . It was superior to imipenem (IPM) in the in vitro antibacterial activities against Haemophilus influenzae, Haemophilus parainfluenzae, Branhamella catarrhalis, Staphylococcus aureus including MRSA, Klebsiella pneumoniae, Serratia marcescens and Escherichia coli . PAPM had antibacterial activities almost equal to those of IPM against Streptococcus pneumoniae and Enterococcus spp . Against Pseudomonas aeruginosa, however, its antibacterial activity was about 1/4 that of IPM . The clinical usefulness of PAPM/BP was studied by dissolving it in a solution containing lactate and administering the solution by intravenous drip infusion to 12 cases of respiratory tract infections . Out of 11 cases with respiratory tract infections excluding cytomegalovirus pneumonia, the efficacy rate was 90.9%, with 4 cases of excellent and 6 cases of good responses . In terms of its bacteriological efficacies, eradication of pathogenic bacteria including super-infection were observed in 2 out of 4 strains, but 2 strains of P . aeruginosa remained unchanged . Six strains appeared as superinfected bacteria during and after administration of this preparation substituting original pathogens . Side-effects were not observed in the 12 cases, and in laboratory tests, slight transient increases of S-GOT and S-GPT were found in 1 case . In conclusion, PAPM/BP is a very useful parenteral antibiotic against respiratory tract infections and can be one of the drugs of the first choice.

Antimicrob Agents Chemother, 1992 Feb, 36(2), 467 - 9
Identification of a ROB-1 beta-lactamase in Haemophilus ducreyi; Maclean IW et al.; A collection of 100 clinical isolates of Haemophilus ducreyi from Thailand were all found to harbor a 5.4-kb plasmid, designated pTH126, which was shown to contain the bla ROB-1 gene . Restriction enzyme analysis and DNA-DNA hybridization studies confirmed that pTH126 was similar to the ROB-1 beta-lactamase plasmid pVM105 from Actinobacillus pleuropneumoniae . In approximately one-half of the isolates, pTH126 was found together with pHD131, which mediates TEM-1 beta-lactamase production.

Zentralbl Bakteriol, 1992 Feb, 276(3), 429 - 36
Antibody production in infants born to HIV-1-infected mothers; Guerra E et al.; Naturally occurring antibodies to polysaccharide antigens of pathogens commonly isolated from HIV-1-infected subjects were analyzed in serially collected sera of children born to seropositive mothers . Purified polysaccharides from type 14 Streptococcus pneumoniae, group C Neisseria meningitidis, type b Haemophilus influenzae, glucomannoprotein from Candida albicans and diphtheria toxoid antigens were used in an ELISA test to assess antibody levels . A significant rise of anti-pneumococcus antibody titres was noticed both in HIV-1-infected and in non-HIV-1-infected children aged 18 months or more . Anti-C . albicans and anti-group C N . meningitidis antibodies were elevated only in HIV-1-infected children older than 12 months . Anti-type b H . influenzae antibodies remained at low titres in both groups . Anti-diphtheria toxoid antibodies, analyzed as a model of humoral response to a protein antigen, were similar in both groups of HIV-1-infected and noninfected children.

Am J Vet Res, 1992 Feb, 53(2), 175 - 9
Immune response of cattle to Haemophilus somnus lipid A-protein conjugate vaccine and efficacy in a mouse abortion model; Inzana TJ et al.; Immunogenicity of the lipid A component of Haemophilus somnus lipooligosaccharide in cattle and mice was examined after purification, detoxification, and covalent conjugation to a protein carrier . After 2 inoculations, a substantial antibody response was induced in most cattle to lipid A and the protein carrier . To determine whether antibodies to lipid A would be protective, 5 x 10(7) colony-forming units of H somnus strain 649 were administered IV to endotoxin-responsive (C3H/HeN) mice . In one study, 8 of 13 C3H/HeN mice aborted when inoculated . In contrast, abortion did not result when mice were inoculated with the same dose of an isolate of H somnus normally found in the prepuce or with the rough mutant Escherichia coli J5 . In addition, endotoxin-nonresponsive (C3H/HeJ) mice were significantly (P = 0.03) more resistant to abortion by strain 649 than were C3H/HeN mice, but inoculated C3H/HeN mice were only slightly more resistant to H somnus abortion, compared with control mice . Although a large antibody response to lipid A was detected, there was no significant difference in the immunized group between mice that aborted and mice that delivered normally . Thus, lipooligosaccharide and other properties of virulent H somnus strains may contribute to abortion in mice.

Diagn Microbiol Infect Dis, 1992 Feb, 15(2), 157 - 9
Osteomyelitis and septic arthritis caused by Haemophilus influenzae, type f, in a young girl; Chusid MJ et al.; A 4-year-old girl with Legg-Calve Perthes' disease and immunoglobin G1 subclass deficiency developed osteomyelitis of the proximal femur and septic arthritis of the hip secondary to Haemophilus influenzae, type f . This microorganism is a rare cause of invasive infections in children, primarily of the central nervous system (CNS) and respiratory track . It has not previously been associated with bone and joint infections.

Diagn Microbiol Infect Dis, 1992 Feb, 15(2), 141 - 4
A comparison of antimicrobial activity of ofloxacin, L-ofloxacin, and other oral agents for respiratory pathogens; Cherubin CE et al.; The attainable inhibitory ratios (AR) for oral antibiotics were calculated by using literature reports of concentrations attained in respiratory secretions for amoxicillin-clavulanic acid (AMX/CA), ofloxacin (OFL), L-ofloxacin (L-OFL), cefuroxime (CEFU), ciprofloxacin (CIP), and enoxacin (ENO), and using microdilution minimum inhibitory concentration data of these antimicrobials against the common bacterial respiratory pathogens . AR of each antibiotic against the pathogens was expressed as multiples of the MICs achieved at the respiratory site . Bacteria tested included Staphylococcus aureus, group-A and group-B streptococci, Viridans streptococci, Streptococcus pneumoniae, Brahamella catarrhalis, Klebsiella pneumoniae, Eikenella corrodens, Haemophilus influenzae, H . parainfluenzae, Pseudomonas aeruginosa, and Legionella pneumophila . The antimicrobials with the narrowest spectrum of activity were amoxicillin-clavulanic acid and cefuroxime which had high attainable inhibitory ratios only against Gram-positive cocci . Ofloxacin and L-oflaxacin were among the quinolones with the highest overall ARs against respiratory pathogen, including, L . pneumophila, H . influenzae, and B . catarrhalis . All agents showed no, or inadequately low ARs for P . aeruginosa.

Mol Microbiol, 1992 Feb, 6(4), 547 - 54
Outer membrane protein P6 of Haemophilus influenzae binds to its own gene; Sikkema DJ et al.; Outer membrane protein P6 is an important antigen expressed on the surface of all strains of Haemophilus influenzae . The predicted amino acid sequence of P6 contains a region of alpha helices that shares sequence identity with a family of helix-turn-helix DNA-binding proteins . A search for sequence-specific binding sites that resemble an operator region within the gene revealed a sequence with striking homology to the consensus operator sequence for lambda Cro and repressor . To test the hypothesis that P6 binds its own gene, purified P6 on nitrocellulose was probed with plasmid DNA containing the P6 gene . P6 bound the P6 gene in this Southwestern blot assay . To further test the observation, gel shift analysis was performed . Gel shift assays using a P6-specific monoclonal antibody demonstrated that P6 in crude cell extracts binds to the region of the gene containing the putative binding site . Competition with a synthetic oligonucleotide corresponding to the putative binding site inhibited binding of P6 to the P6 gene on nitrocellulose and in the gel shift assay . In addition, this oligonucleotide bound directly to P6 on nitrocellulose . Finally, DNase footprinting confirmed that P6 bound specifically to the same region of the P6 gene . These results indicate that P6 binds to a sequence-specific site within its own gene, suggesting that P6 regulates its own expression . This represents the first example of a Gram-negative outer membrane protein binding to its own gene and has potentially important implications as a mechanism for regulation of expression of outer membrane antigens.

APMIS, 1992 Feb, 100(2), 142 - 6
Relation between enzyme-linked immunosorbent assay and radioimmunoassay for detection of antibodies to the capsular polysaccharide of Haemophilus influenzae type b; Kristensen K et al.; The measurement of antibodies to the capsular polysaccharide (PRP) of Haemophilus influenzae type b (Hib) is important because vaccines inducing such antibodies are now available . We developed and evaluated an enzyme-linked immunosorbent assay (ELISA) for detection of these antibodies based on direct coating of the plates with tyraminated PRP . The assay fulfilled the requirements for parallel line assays; it was sensitive, specific, and reproducible with a coefficient of variation between days of 19% . Results from the ELISA were compared with results from radioimmunoassay and a correlation coefficient of 0.93 was found . Results obtained by the two methods were proportional and the relation was independent of the antibody level . The relation between them was also unaffected by the contribution of different antibody isotypes, indicating that these were measured to the same extent by both methods . ELISA employing direct coating of the plates with tyraminated PRP represents a useful alternative for detection of antibodies when studying immunogenicity of Hib vaccines.

J Clin Microbiol, 1992 Feb, 30(2), 386 - 90
Molecular epidemiology of Haemophilus influenzae type b in the Gambia; Bijlmer HA et al.; One hundred two invasive and 64 noninvasive isolates of Haemophilus influenzae were collected in the course of a 2-year prospective field study on the epidemiology of H . influenzae meningitis in The Gambia . The isolates were serotyped, biotyped, and subtyped by outer membrane protein (OMP) profile analysis (OMP subtyping) . H . influenzae meningitis was found to be caused by serotype b (95%) . In invasive disease, serotype a, although present in the throat of healthy children, caused only occasionally (5.9%) disease . The distribution of biotypes of H . influenzae appeared to be very similar to that found outside The Gambia . A distinct pattern of OMP subtypes, different from other parts of the world, is prevalent in H . influenzae type b (Hib) in The Gambia . OMP subtypes 2, 4, 5, 8, and 9 were observed to be predominant . These subtypes, except subtype 2, have not been described . L subtypes (subtypes 2, 4, and 8) were associated with invasive disease, whereas non-L subtypes (subtypes 5 and 9) were found more often in healthy carriers (P less than 0.001) . A significant difference in geographical distribution was found in subtypes of noninvasive Hib strains (P less than 0.05) . We conclude that in The Gambia H . influenzae invasive disease is caused mainly by type b strains with a limited number of OMP subtypes, which are different from the subtypes found elsewhere in the world . These data are important for the surveillance of Hib disease in developing countries and are baseline data for a Hib polyribosyl-ribitolphosphate-conjugated vaccine trial in The Gambia . Alternative Hib OMP vaccines should include a set of representative OMPs.

Gan To Kagaku Ryoho, 1992 Feb, 19(2), 184 - 8
{Respiratory infections associated with lung cancer}; Watanabe A et al.; We have analyzed the clinical significance of secondary infections associated with lung cancer patients . The incidence of secondary infections was 51.4% in 214 in-patients with lung cancer admitted to our institution in 1988 and 1989, and almost all of them had respiratory tract infections . The incidence was high in patients with cell types other than adenocarcinoma, and in those with hypoproteinemia, impaired cellular immunity and obstruction of the airway . The prognosis in patients with infection was much poorer than that in patients without infection . Major causative pathogens were Staphylococcus aureus including methicillin-resistant S . aureus (MRSA), Haemophilus influenzae, Klebsiella spp . and Pseudomonas aeruginosa . These pathogens except for H . influenzae were isolated at the terminal stage, in cases with airway obstruction and in post cancer-chemotherapeutic phase . The efficacy rate of 194 chemotherapeutic regimens against infection was 57.7% . Although the efficacy rate in 1988 and 1989 exceeded that in the 1970s, there was no significant difference in the efficacy rate between monotherapy (57.1%) and combined therapy (59.3%) . The effectiveness was very poor for infections caused by P . aeruginosa and MRSA, or for cases with airway obstruction and marked impairment of pulmonary blood flow . The above results showed that a new combined therapy as well as the measures to improve the general condition of compromised hosts are required in the treatment of secondary infections in these patients.

Infect Immun, 1992 Feb, 60(2), 385 - 91
Characterization of an 18,000-molecular-weight outer membrane protein of Haemophilus ducreyi that contains a conserved surface-exposed epitope; Spinola SM et al.; Identification of antigenically conserved surface components of Haemophilus ducreyi may facilitate the development of reagents to diagnose and prevent chancroid . A hybridoma derived from a mouse immunized with nontypeable Haemophilus influenzae produced a monoclonal antibody (MAb), designated 3B9, that bound to 35 of 35 H . ducreyi strains isolated from diverse geographic regions . The MAb 3B9 bound to a non-heat-modifiable H . ducreyi outer membrane protein (OMP) whose apparent molecular weight was 18,000 (the 18K OMP), and the 3B9 epitope did not phase vary at a rate of greater than 10(-3) in H . ducreyi . In immunoelectron microscopy, the 3B9 epitope was surface exposed, and there was intrastrain and interstrain variability in the amount of 3B9 labelling of whole cells . The MAb 3B9 cross-reacted with many species of the family Pasteurellaceae and bound to the 16.6K peptidoglycan-associated lipoprotein (P6 or PAL) of H . influenzae . Unlike P6, the 18K OMP did not copurify with peptidoglycan . In Western blots (immunoblots), five of seven serum samples obtained from patients with chancroid and four of five serum samples obtained from patients with other genital ulcer diseases at the time of presentation contained antibodies that bound to the 18K OMP . In a competition enzyme-linked immunosorbent assay, four of these serum samples inhibited the binding of 3B9 to H . ducreyi by more than 50% . We conclude that members of Pasteurellaceae expressed a conserved epitope on OMPs that sometimes had different physical characteristics . Patients with chancroid usually have antibodies to the 18K OMP and the 3B9 epitope that may have resulted from infection with H . ducreyi or previous exposure to other Haemophilus or Actinobacillus sp . strains.

Eur J Surg, 1992 Feb, 158(2), 105 - 8
Lower respiratory tract infections after abdominal operations: epidemiology and risk factors; Oller Sales B et al.; OBJECTIVE: To find out the incidence and aetiology of lower respiratory tract infections after abdominal operations and identify predisposing factors . DESIGN: Prospective open study . SETTING: Department of General Surgery, Hospital Germans Trias i Pujol, Barcelona, Spain . SUBJECTS: 2,083 patients having abdominal operations between March 1985 and June 1987 excluding splenectomies, and those requiring thoracoabdominal incisions . MAIN OUTCOME MEASURES: The presence of three or more of the following: temperature of 38 degrees C or more, cough with mucopurulent sputum, raised white cell count, or changes on the chest radiograph or bronchogram . RESULTS: 50 patients (2.4%) developed lower respiratory tract infections . Micro-organisms were isolated from 15 (30%), the most common being Haemophilus influenzae . The most important risk factors were American Society of Anesthesiologist's grade, duration of anaesthesia, age, and operations on the upper gastrointestinal tract . CONCLUSION: Further work is needed to investigate other possible predisposing factors and develop a predictive score.

Zentralbl Veterinarmed B, 1992 Feb, 39(1), 59 - 64
Fimbriae and membranes on Haemophilus parasuis; Munch S et al.; In the electron microscope an additional layer (glycocalix) of the cell wall and fimbriae on Haemophilus parasuis were shown in thin sections of the infected CAM which have their origin on the CM of the Haemophilus parasuis-cells . No fimbriation was seen after conventional cultivation.

Scand J Immunol, 1992 Feb, 35(2), 137 - 48
In vitro activation of human T lymphocytes by Haemophilus influenzae type b capsular polysaccharides; Peeters CC et al.; Polyribosilribitolphosphate (PRP), the capsular polysaccharide from Haemophilus influenzae type b, is a T-cell-independent type 2 antigen . In vitro culture of adult peripheral blood T cells with 15 micrograms/ml PRP leads to induction of interleukin-2 receptor (IL-2R) expression on up to 10% of T cells . These cells are CD4+ and carry the alpha beta T-cell receptor . PRP, at concentrations above 1-5 micrograms/ml, can also induce in vitro proliferation of both adult and neonatal T cells . We conclude that PRP acts as a human T-cell mitogen . The in vitro proliferative response as well as IL-2R expression was studied in T cells derived from adults after vaccination with native PRP, with PRP conjugated to a carrier protein, or with diphtheria toxoid . Vaccination with conjugated PRP decreased the doses of PRP required for in vitro induction of IL-2R expression and T-cell proliferation . This indicates that vaccination with PRP conjugated to a carrier protein improves the in vitro T-cell response to PRP activation.

Infect Immun, 1992 Feb, 60(2), 374 - 9
Comparison of hemagglutinating pili of Haemophilus influenzae type b with similar structures of nontypeable H . influenzae; Gilsdorf JR et al.; Thirty-eight clinical isolates of nontypeable Haemophilus influenzae were tested for the presence of hemagglutinating pili similar to those of H . influenzae type b (Hib) that mediate buccal epithelial cell adherence . Four endogenously hemagglutinating (HA+) strains were identified, and eight additional HA+ variants were obtained from HA- strains by erythrocyte enrichment . All 12 HA+ nontypeable H . influenzae isolates bound antisera directed against denatured pilins of Hib, but none bound antisera against assembled native pili of Hib . In erythrocyte- and buccal-cell-binding assays, HA+ nontypeable H . influenzae binding was reduced compared with HA+ Hib binding and was not significantly different from HA- nontypeable H . influenzae binding . Both HA- and HA+ nontypeable H . influenzae binding was increased over binding of HA- Hib . HA+ nontypeable H . influenzae strains agglutinated adult erythrocytes that possess the Anton antigen, which is thought to be the receptor for Hib pili, and did not agglutinate cord or Lu(a-b-) dominant erythrocytes, which lack the Anton antigen . Electron microscopy of HA- and HA+ variants of three nontypeable H . influenzae strains showed few or no surface appendages on the HA- organisms, but piluslike structures were seen on many organisms from two HA+ nontypeable H . influenzae strains and on a few organisms from one strain . Thus, nontypeable H . influenzae appears to possess structures that are immunologically similar to the pilins that make up the hemagglutinating pili of Hib . However, nontypeable H . influenzae appears to also possess mechanisms for erythrocyte and buccal cell adherence that are not directly correlated with the presence of a hemagglutinating pilus.

Nihon Kyobu Shikkan Gakkai Zasshi, 1992 Feb, 30(2), 201 - 8
{Respiratory tract infections in the elderly, advances and limitations in the diagnosis and treatment}; Watanabe A; Advances and limitations in the diagnosis and treatment of respiratory tract infections were discussed in relation to the prognosis of the elderly patients . Haemophilus influenzae and Streptococcus pneumoniae are the major pathogens in the community-acquired respiratory tract infections . On the other hand, methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa are the major pathogens in the nosocomial respiratory tract infections . Detection of MRSA-PBP genes and antibiotic sensitivity tests are important for the diagnosis of MRSA . Vancomycin or arbekacin is the first-choice antibiotic for the treatment of severe infection caused by MRSA, and a combination therapy using one of the above agents and a partner antibiotic is necessary in some cases of MRSA infections . Reports concerning the significance of anaerobic bacteria in respiratory tract infections in Japan have been rare, presumably because procedures to recover anaerobic bacteria from specimens other than sputum, for example transtrancheal aspiration (TTA), bronchoscopic procedure and transcutaneous lung biopsy, are required for the diagnosis of the anaerobic respiratory tract infections . Nowadays, identification of cytomegalovirus (CMV) is a prerequisit for the rapid diagnosis of CMV infection . Therefore attempts are being made to detect a specific substance, for example messenger RNA during the stage of reactivation of CMV . Prophylaxis as well as treatment is necessary for the control of acute exacerbation of chronic respiratory tract infections . In this regard, long-term administration of a small dose of erythromycin or new-quinolone is promising.

Diagn Microbiol Infect Dis, 1992 Feb, 15(2), 145 - 50
Interpretive criteria and quality control guidelines for lomefloxacin and meropenem in susceptibility tests of Haemophilus influenzae using Haemophilus test medium; Pfaller MA et al.; Lomefloxacin and meropenem were tested in a multilaboratory study to establish susceptibility testing interpretive criteria and quality control (QC) guidelines for Haemophilus influenzae using Haemophilus test medium (HTM) . Interpretive criteria were established by using triplicate testing of 102 representative H . influenzae strains . Only a susceptible category was proposed for lomefloxacin (greater than or equal to 22 mm and less than or equal to 2 micrograms/ml) and meropenem (greater than or equal to 13 mm and less than or equal to 4 micrograms/ml) due to the lack of resistant isolates . QC range for H . Influenzae ATCC 49247 were established using multiple HTM agar and broth base lots, three disk lots for each drug, and a number of test replicates consistent with the National Committee for Clinical Laboratory Standards M23-T guideline.

Clin Pharm, 1992 Feb, 11(2), 137 - 52
Clarithromycin and azithromycin: new macrolide antibiotics; Piscitelli SC et al.; The chemistry, mechanism of action, antimicrobial spectrum, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage and administration of clarithromycin and azithromycin are described . Clarithromycin and azithromycin are new macrolide antibiotics that are similar in structure to erythromycin . Compared with erythromycin, clarithromycin demonstrates increased activity against Staphylococcus aureus, streptococci, Legionella pneumophila, Moraxella catarrhalis, and Chlamydia trachomatis . Clarithromycin also has in vitro activity against Mycobacterium avium complex (MAC) and Toxoplasma gondii . Azithromycin has increased gram-negative activity compared with erythromycin, including activity against Haemophilus influenzae, while maintaining activity against gram-positive organisms . Azithromycin also has activity against sexually transmitted organisms including Chlamydia trachomatis . The pharmacokinetic profiles of clarithromycin and azithromycin are characterized by good oral bioavailability, excellent tissue penetration and persistence, and long elimination half-lives, which allow for once-daily or twice-daily dosing . Initial data show that clarithromycin and azithromycin are effective for the treatment of upper-respiratory-tract and lower-respiratory-tract infections and infections of the skin and skin structures . Azithromycin has been shown to be effective for the treatment of sexually transmitted diseases caused by Chlamydia trachomatis . Clarithromycin and azithromycin have been used to treat MAC and Toxoplasma infections in patients with the acquired immunodeficiency syndrome . The most frequently reported adverse effects for both agents have been nausea, diarrhea, and abdominal pain . Oral formulations of clarithromycin and azithromycin have recently been approved by the FDA . Clarithromycin and azithromycin are new macrolide antibiotics that have potential advantages over erythromycin; however, the role of these agents will be better defined as results of more ongoing trials become available for evaluation.

Infect Immun, 1992 Feb, 60(2), 618 - 22
Insertion sequence IS1016 and absence of Haemophilus capsulation genes in the Brazilian purpuric fever clone of Haemophilus influenzae biogroup aegyptius; Dobson SR et al.; Brazilian purpuric fever (BPF) strains of Haemophilus influenzae biogroup aegyptius form a clone of organisms distinct from more innocuous, conjunctivitis-associated isolates . There has been controversy over whether the virulence of BPF strains might derive from the presence of a polysaccharide capsule analogous to that found in conventional invasive H . influenzae, a controversy fuelled by the observation (G . M . Carlone, L . Gorelkin, L . L . Gheesling, A . L . Erwin, S . K . Hoiseth, M . H . O . Mulks, S . P . Connor, R . S . Weyant, J . Myrick, L . Rubin, R . S . Mumford III, E . H . White, R . J . Arko, B . Swaminathan, L . M . Graves, L . W . Mayer, M . K . Robinson, S . P . Caudill, and the Brazilian Purpuric Fever Study Group, J . Clin, Microbiol . 27:609-614, 1989) that a capsulation DNA probe from H . influenzae type b hybridized uniquely to BPF strains . In this work, the basis for this hybridization has been established as the possession by BPF strains, but not by non-BPF strains, of the Haemophilus insertion element IS1016 . Although IS1016 is associated with the capsulation locus in some Haemophilus spp., a Southern hybridization study suggests that in BPF strains there are no capsulation genes.

Commun Dis Rep CDR Rev, 1992 Jan 31, 2(2), R13 - 6
A survey of invasive Haemophilus influenzae infections; Nazareth B et al.; A survey of invasive H . influenzae infections has been underway in six regions of England and Wales since September 1990 . In the first year, there were 433 cases of which 362 (84%) were due to H . influenzae type b (Hib) . The majority of Hib infections were in children aged less than 5 years; there being an annual incidence of 26.4/100,000 in this age group . Meningitis occurred in 56% of cases of Hib infection . The results confirm previous evidence of the need to incorporate Hib vaccination into the childhood immunisation schedule . The ongoing survey data will provide useful information to assess the impact of an Hib immunisation programme.

J Immunol Methods, 1992 Jan 21, 146(1), 129 - 37
An improved haemolytic plaque assay for the detection of cells secreting antibody to bacterial antigens; Barington T et al.; Recent advances in the development of conjugate polysaccharide vaccines for human use have stimulated interest in the use of assays detecting antibody-secreting cells (AbSC) with specificity for bacterial antigens . Here we present improved haemolytic plaque-forming cell (PFC) assays detecting AbSC with specificity for tetanus and diphtheria toxoid as well as for Haemophilus influenzae type b and pneumococcal capsular polysaccharides . These assays were found to be less time consuming, more economical and yielded 1.9-3.4-fold higher plaque numbers than traditional Jerne-type PFC assays . In the case of anti-polysaccharide AbSC of the IgG isotype, the increase was as high as 7.4-11.8 times . Evidence is presented that the pronounced improvement in the detection of the latter is due to the presence of aggregating anti-IgG antibody from the beginning of the assay . It is proposed that in the case of low affinity of anti-polysaccharide antibodies aggregation of secreted monomeric antibody (IgG) is critical for plaque formation and increases the avidity of binding to target cells.

Epidemiol Rev, 1992, 14, 243 - 67
Epidemiology of pertussis and reactions to pertussis vaccine; Hodder SL et al.; It remains clear that pertussis is a dangerous infectious disease that is well-controlled in industrialized countries by widespread immunization . In the developing world, it remains a source of high morbidity and mortality because of previously inadequate immunization programs . However, because of the intense efforts of the World Health Organization's Expanded Programme on Immunization, the effects of pertussis have already been ameliorated and show promise of being within a decade of approximating the situation in the developed world . Pertussis can be controlled only by immunization; other measures such as antimicrobial therapy offer negligible benefit . A problem that has been addressed in recent years is the excessive reactivity of whole-cell pertussis vaccine, which undoubtedly includes components of the organism that are irrelevant to the induction of immunity and are excessively reactive . Although epidemiologic studies appear to have largely, if not completely, absolved pertussis vaccine of responsibility for inducing death or permanent neurologic disability, a less reactive vaccine is highly desirable, not only to promote acceptance of a full course of immunization for the world's children but also for simple humanitarian reasons . Additionally, it has become evident that, because of waning immunity, pertussis increasingly occurs in adults . A less reactive vaccine would offer opportunity for reinforcement of immunity beyond childhood . The development of better, though as yet incomplete, understanding of the biology of Bordetella pertussis and its relation to humanity offers the opportunity for the production of less reactive vaccines free of irrelevant components . Acellular pertussis vaccines have been used exclusively in Japan for more than 10 years, and one such preparation, combined with diphtheria and tetanus toxoids, was licensed in the United States in late 1991 for use as the fourth and fifth doses of DTP, given at 15 months and prior to school entry . Field trials of this and other acellular DTP preparations are currently under way to determine their clinical efficacy in infants . It is probable that, within a very few years, whole-cell pertussis vaccine will be replaced by these newer preparations and that, in addition, the acellular product will be combined with other antigens, such as Haemophilus influenzae type b vaccine.

Int J Syst Bacteriol, 1992 Jan, 42(1), 12 - 8
Application of multivariate analyses of enzymic data to classification of members of the Actinobacillus-Haemophilus-Pasteurella group; Myhrvold V et al.; Outer membrane vesicles and fragments from Actinobacillus actinomycetemcomitans, Actinobacillus lignieresii, Actinobacillus ureae, Haemophilus aphrophilus, Haemophilus paraphrophilus, Haemophilus influenzae, Haemophilus parainfluenzae, Pasteurella haemolytica, and Pasteurella multocida were isolated and examined semiquantitatively for 19 enzyme activities by using the API ZYM micromethod . The enzyme contents of vesicles and fragments were compared with the enzyme contents of whole cells of the same organisms . Enzymic data were analyzed by using principal-component analysis and soft independent modeling of class analogy . This technique allowed us to distinguish among the closely related organisms A . actinomycetemcomitans, H . aphrophilus, and H . paraphrophilus . A . actinomycetemcomitans was divided into two groups of strains . A . lignieresii fell outside or on the border of the A . actinobacillus class . A . ureae, H . influenzae, H . parainfluenzae, P . haemolytica, and P . multocida fell outside the A . actinomycetemcomitans, H . aphrophilus, and H . paraphrophilus classes.

South Med J, 1992 Jan, 85(1), 14 - 8
Oral ofloxacin therapy for lower respiratory tract infection; Gentry LO et al.; We made an open, noncomparative evaluation of ofloxacin, 400 mg orally bid for 10 days, in 98 subjects with community-acquired pneumonia or pathogen-confirmed bronchitis . Thirty-nine (40%) of the subjects were treated in the hospital and 59 (60%) were treated as outpatients . The mean age of those treated was 56.2 years; 73 (74%) of the subjects either were more than 60 years old or had a history of chronic obstructive pulmonary disease, or both . There were 95 organisms initially isolated in sputum, aspirate, or lavage fluid; all were susceptible to ofloxacin, and none acquired resistance during therapy . Haemophilus influenzae was the most common pathogen (19 isolates), followed by Streptococcus pneumoniae (18) and Staphylococcus aureus (10) . Clinical responses included cure in 70 patients (71%), improvement in 26 (27%), and failure in two (2%) . After 10 days of therapy, pathogens persisted in two cases; in one case, Streptococcus salivarius was isolated, though it remained susceptible to ofloxacin, and in the other, Klebsiella pneumoniae was accompanied by superinfection due to a resistant strain of Serratia marcescens . We included in this study three confirmed cases of atypical pneumonia successfully treated with ofloxacin, two of them due to Mycoplasma pneumonia and one to Legionella pneumophila . Ofloxacin was well tolerated . Our data indicate that ofloxacin is effective and safe as specific and empiric treatment for many lower respiratory tract infections.

J Pediatr, 1992 Jan, 120(1), 84 - 7
Safety and immunogenicity of acellular diphtheria-tetanus-pertussis and Haemophilus conjugate vaccines given in combination or at separate injection sites; Kovel A et al.; This prospective, double-blind, randomized trial compared the immunogenicity and reactogenicity of acellular diphtheria-tetanus-pertussis vaccine and Haemophilus influenzae type b conjugate vaccine-diphtheria toxoid conjugate, given at separate injection sites or at a single site, in 79 children 18 months of age who had received three prior immunizing doses of whole-cell diphtheria-tetanus-pertussis vaccine . No significant differences were observed.

Diagn Microbiol Infect Dis, 1992 Jan, 15(1), 57 - 65
Pneumonia . Patient profiles, choice of empiric therapy, and the place of third-generation cephalosporins; Leedom JM; Choosing appropriate antimicrobial therapy for patients with pneumonia requires knowledge of the etiologic agents seen in specific kinds of patients at specific times and places . For community-acquired pneumonia, there is an important difference in the agents seen in the normal and the compromised host . The normal host most often presents with viral, mycoplasmal, or pneumococcal pneumonia . The exact place of Chlamydia pneumoniae is still under study . A normal host who aspirates is at risk of anaerobic pneumonia . Normal hosts with influenza may acquire superinfection with Streptococcus pneumoniae, Haemophilus influenzae, or Staphylococcus aureus . Under specific epidemiologic conditions, community-acquired pneumonia may be due to Legionella species, Yersinia pestis, Francisella tularensis, Coxiella burnetii, Chlamydia psittaci, a mycotic agent, or tuberculosis . Patients with chronic bronchitis and emphysema are predisposed to H . influenzae, Moraxella catarrhalis, and S . pneumoniae infections . HIV-infected patients are likely to have Pneumocystis carinii pneumonia and pneumonia due to cytomegalovirus, S . pneumoniae, and H . influenzae . Patients with diabetes, nursing-home patients, hospitalized patients, immuno-compromised patients, and patients with recent antibiotic therapy are predisposed to pneumonia due to Gram-negative aerobic bacilli of enteric and environmental origin . Initial therapy should be directed at the likely organism or organisms based on hospital susceptibility surveillance . In the normal host with community-acquired pneumonia, the therapy will often be penicillin G or erythromycin . In the patient predisposed to Gram-negative pneumonia, a third-generation cephalosporin with or without an aminoglycoside is the usual choice.

J Bacteriol, 1992 Jan, 174(1), 17 - 23
Cloning, sequencing, expression, and functional studies of a 15,000-molecular-weight Haemophilus somnus antigen similar to Escherichia coli ribosomal protein S9; Theisen M et al.; Haemophilus somnus is a gram-negative bacterium capable of causing a number of disease syndromes in cattle . This article describes the cloning and characterization of a gene coding for a 15,000-molecular-weight (15K) polypeptide which reacts strongly with antiserum against H . somnus . Analysis of plasmid-encoded polypeptides by polyacrylamide gel electrophoresis showed that the corresponding gene is the second in a transcriptional unit . The first gene codes for a protein with a molecular weight of approximately 17,000 . Using antiserum against the two recombinant proteins, we could show that the natural proteins are predominantly present in purified ribosomes from H . somnus . The nucleotide sequence of both genes and flanking regions has been determined, and the deduced amino acid sequence of the two polypeptides was used to search for sequence homology in the GenBank data base . The 15K polypeptide showed 89% similarity to the Escherichia coli ribosomal protein S9, and the 17K polypeptide showed 94% similarity to the E . coli ribosomal protein L13 . In E . coli, the corresponding genes constitute a bicistronic operon, with the same gene order as that found in H . somnus . A plasmid expressing the 15K protein was found to complement an E . coli rpsI mutation . When a frameshift mutation was introduced into the 15K protein gene, the resulting plasmid failed to complement this rpsI mutation, demonstrating functional homology between the 15K protein and S9 from E . coli . Downstream from the 15K protein gene is located another open reading frame, which could code for a polypeptide with a predicted molecular weight of 24,427 . A protein with a similar molecular weight was detected in minicells containing the recombinant clone . This polypeptide is 69% similar to the stringent starvation protein (Ssp) of E . coli.

Infect Immun, 1992 Jan, 60(1), 19 - 24
Complement component 3 binding to Haemophilus influenzae type b in the presence of anticapsular and anti-outer membrane antibodies; Hetherington SV et al.; Antibodies directed against the capsular polysaccharide (polyribosyl ribitol phosphate {PRP}) or the outer membrane proteins (OMP) of Haemophilus influenzae type b (Hib) promote bactericidal activity, complement 3 (C3) binding, and ingestion by phagocytic cells . To assess the relative contribution of anti-OMP to host defense against Hib, we compared the opsonic activities of anti-PRP and anti-OMP as reflected by the amounts of C3 bound to the bacterial surface . Immunoglobulin G (IgG) fractions containing either anti-PRP or anti-OMP were incubated with Hib in the presence of a C5-deficient complement source . C3, total IgG, and IgG subclasses bound to the bacteria were quantified by enzyme-linked immunosorbent assay . The maximum amount of C3 which could be bound to Hib was greater in the presence of anti-PRP than in the presence of anti-OMP . Also, except at low IgG concentrations, the rate of increase in bound C3 as a function of increasing IgG concentration was greater for anti-PRP than for anti-OMP . Hib-bound anti-OMP consisted primarily of IgG1 and IgG3, whereas bound anti-PRP was primarily IgG1 and IgG2 . Thus, the potential for C3 binding to Hib is greater in the presence of anti-PRP than in the presence of anti-OMP, probably because of the larger number of binding sites available to the former . Nonetheless, OMP appear to provide important targets for opsonic antibody and would be logical components of a PRP-conjugate vaccine or may be efficacious as vaccines against nontypeable H . influenzae.

Srp Arh Celok Lek, 1992 Jan-Feb, 120(1-2), 26 - 30
{Antimicrobial sensitivity of Haemophilus influenzae strains isolated from children}; Petreska-Sibinovska D et al.; Antibiotic susceptibility of 1308 Haemophilus sp . strains isolated in children was evaluated over a 6-year period . Based on their source and clinical presentation all strains were divided in three groups . The first group consisted of 1264 strains obtained by throat and nasal swab; the second of 30 mucosal strains isolated in children manifesting non-invasive infection and the third of 14 invasive strains, Haemophilus influenzae(Hi)tip b, isolated from blood, CSF, pleural and synovial effusion . The isolates of the first and the second group demonstrated high susceptibility (90%) to chloramphenicol, erythromycin, and ceftriaxone, lower (70-90%) ampicillin and trimethoprim-sulfamethoxazole and low susceptibility (less than 25%) to penicillin, lincomycin and cefalexin . Invasive strains of Hi tip b were resistant to multiple drugs, showing susceptibility exclusively to chloramphenicol, erythromycin and ceftriaxone . Guidance for the treatment of the invasive and non-invasive infections and chemoprophylaxis are discussed.

Acta Otolaryngol Suppl, 1992, 493, 69 - 76
Pseudomonas aeruginosa exotoxin A and Haemophilus influenzae type b endotoxin . Effect on the inner ear and passage through the round window membrane of the chinchilla; Lundman L et al.; Pseudomonas aeruginosa exotoxin A was applied to the round window membrane of the chinchilla in concentrations ranging from 1 microgram/ml to 1 mg/ml . Haemophilus influenzae type b endotoxin (45,000 endotoxin units/ml) was applied in the same way . Five animals were also subjected to blocking of the Eustachian tube, 3 to 8 months earlier, resulting in serous otitis media and exotoxin A (1 mg/ml) was applied into the round window niche of these animals . Effects on the inner ear was recorded with quantitative morphology (hair cell counting) and electrophysiologically (action potential threshold measurements) 4 weeks after application of exotoxin A . Concentrations of exotoxin A in perilymph was measured with ELISA and concentration of endotoxin in perilymph was measured with Limulus Amoebocyte Lysate and Quantitative Chromogenic Limulus Amebocyte Lysate . Four weeks after application of exotoxin A at a concentration of 10 micrograms/ml severe inner ear damage could be demonstrated . No inner ear damage was demonstrated when lower concentrations were used . Passage into the inner ear could only be demonstrated after exposure of the round window membrane to an exotoxin A concentration of 1 mg/ml . Round window membranes affected by chronic inflammation were shown to be less permeable to exotoxin A, thus indicating that thickening of the round window membrane may have a protective effect on the inner ear . A low passage rate into the inner ear was demonstrated after endotoxin exposure . It may be concluded that small amounts of exotoxin A passing through the round window membrane may cause inner ear damage . The passage rates, however, for both exotoxin A and endotoxins are low.

Acta Derm Venereol Suppl (Stockh), 1992, 174, 1 - 20
Mechanisms of skin adherence, penetration and tissue necrosis production by Haemophilus ducreyi, the causative agent of chancroid; Abeck D et al.; Haemophilus ducreyi (H . ducreyi) strains, representing both reference strains and low-passage isolates, were investigated in terms of surface structures and enzymatic equipment . The interaction of these factors with host tissue was analysed using new in vitro- and in vivo-models . By electron microscopy studies there was no evidence of an extracellular capsule or surface appendages such as pili or flagella . Interaction of all isolates tested with the lectin Phaseolus vulgaris suggests N-acetyl-D-glucosamine units as common structural features of H . ducreyi cell envelope polysaccharide . In attachment to epithelial cells more than one hemagglutinin might be implicated as different haemagglutination patterns could be observed whereby the activity was not heat-labile, but was abolished by formaldehyde . Hydrophobic interactions might be of importance as well as strains showed a wide range of reactions from hydrophobic to hydrophilic, low hydrophobicity being more marked with the older strains . No elaboration of degradative enzymes based on the measurement of enzymatic activity using insoluble dye-protein complexes could be detected in case of H . ducreyi, using Azocoll and Remazol Brilliantblue hide powder for detection of proteolytic activity and elastinorcein for detection of elastase activity . In vitro studies using human keratinocytes and Vero cells did not show any morphological changes when incubated with H . ducreyi culture filtrates . In vivo studies with a new mouse model for H . ducreyi infection could confirm the results of the in vitro studies . Mere contact to undamaged skin both of whole cell organisms, live or heat-killed, and of culture filtrates did not lead to any reaction or even damage of mouse skin . However, when the outer epidermal layer was overcome by intradermal injection of shaved mice ulcers developed . Tissue necrosis production was not bound to live organisms as dead ones showed the same effect . There is great evidence that this tissue necrosis is associated with H . ducreyi lipopolysaccharide (LPS) because intradermal injection of purified H . ducreyi LPS lead to the same reaction pattern . For the first time a cell mediated immune response could be demonstrated in case of H . ducreyi infection as different antigen preparations of H . ducreyi isolates induced proliferation of lymphocytes isolated from healthy unexposed individuals and from a chancroid-sensitized male . In the latter case measured cell responses were much stronger . The dose-dependent phenomenon was associated with interleukin-2 production . In summary, H . ducreyi isolates do not exhibit cytotoxic effects on the epithelial cells of the skin.(ABSTRACT TRUNCATED AT 400 WORDS)

Curr Med Res Opin, 1992, 12(10), 631 - 9
Cefetamet pivoxil in community-acquired pneumonia: an overview; Kissling M; A total of 305 patients with community-acquired pneumonia have participated in comparative or non-comparative studies involving cefetamet pivoxil . Of these, 211 (55 adults and 156 children) were involved in a series of open, prospective, comparator-controlled, multi-centre studies . Adults were randomized to receive either cefetamet pivoxil 1000 mg twice daily or amoxycillin 750 mg 3-times daily for 10 days . Children received either cefetamet pivoxil 10 mg/kg twice daily, cefetamet pivoxil 20 mg/kg twice daily or cefaclor 10 mg/kg 3-times daily for 7 to 8 days . The remaining 94 patients were treated openly with cefetamet pivoxil, with most patients receiving cefetamet pivoxil 500 mg twice daily for an average of 10 days; an elderly sub-group of these patients aged 70 to 103 years received therapy for an average of 11 days . The main causative organisms isolated were Streptococcus pneumoniae and Haemophilus influenzae . In adult patients, a successful clinical outcome was achieved in 100% of assessable patients receiving cefetamet pivoxil 1000 mg twice daily, and about 90% in those receiving 500 mg twice daily . The success rate in children was 98% for both dose levels of cefetamet pivoxil and 90% for those receiving cefaclor . In elderly patients, the percentage was 78% for the 500 mg twice daily patients . Thus, the standard dose of cefetamet pivoxil (500 mg twice daily in adults, 10 mg/kg twice daily in children) was well tolerated and proved to be at least as effective as the comparator drugs which were given 3-times a day.

J Hyg Epidemiol Microbiol Immunol, 1992, 36(1), 93 - 104
Determination of Haemophilus influenzae and Haemophilus parainfluenzae susceptibility to ampicillin and other antibiotics; Urbaskova P et al.; A sample comprising 40 H . influenzae and 74 H . parainfluenzae strains was used to verify methods for determining susceptibility to antibiotics . Modified Levinthal agar proved to be suitable for the agar dilution and agar diffusion method, while brain heart infusion with the thermally released components of sheep blood (X and V factor) and lysed horse blood performed well in the dilution micromethod . The iodometric method served well for beta-lactamase production . A substantial proportion of strains was resistant to penicillin, erythromycin, roxitromycin and sulfamethoxazole . Ampicillin susceptibility was of crucial importance . Resistance was largely due to beta-lactamase production . Since there are ampicillin-resistant strains which fail to produce beta-lactamase, it is necessary either to determine the MIC value or use a disk with 2 micrograms ampicillin . A disk containing 10 micrograms ampicillin may yield a false positive result.

Chemotherapy, 1992, 38(1), 7 - 13
Killing rate and growth rate comparison for newer beta-lactamase-stable oral beta-lactams against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis; Yourassowsky E et al.; A new method of data presentation that takes into account the relationship between growth and killing rate was used to evaluate the comparative in vitro bactericidal activity of cefpodoxime, cefuroxime, cefixime and an amoxicillin/clavulanic acid combination against Streptococcus pneumoniae and beta-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis . For each strain, the viable count decrease (log CFU/ml) after 6 h of exposure to different antibiotic concentrations was plotted against the viable count increase in the control culture, over the same time . Higher killing rates than those predicted by growth rates were defined as a positive balance; lower rates than those predicted by growth rates were defined as a negative balance . The activity of the 4 drugs against S . pneumoniae and M . catarrhalis was characterized by a positive balance . Conversely, the 3 cephalosporins showed a negative balance for H . influenzae.

Chemotherapy, 1992, 38(1), 36 - 45
In vitro activity of a new broad-spectrum, beta-lactamase-stable oral cephalosporin, cefixime, in comparison with other drugs, against Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis and Streptococcus pneumoniae; Stefani S et al.; Cefixime, a new orally absorbed iminomethoxyaminothiazolyl cephalosporin, was tested against some microorganisms involved in upper and lower respiratory tract infections such as Haemophilus (influenzae and parainfluenzae), Moraxella catarrhalis and Streptococcus pneumoniae, isolated in the period from November 1990 to April 1991 . Its activity was compared to nine other antimicrobial agents: erythromycin, trimethoprim-sulfamethoxazole, ampicillin, amoxicillin-clavulanate, cefaclor, ceftazidime, ceftriaxone, cefotaxime and ofloxacin . Cefixime inhibits 90% of S . pneumoniae, H . influenzae and H . parainfluenzae, both beta-lactamase producers (BLP) or not (NBLP) at concentrations of less than 0.25 mg/l . It inhibits 90% of M . catarrhalis (BLP and NBLP) at concentrations of less than 1 mg/l . In general, cefixime has a superior in vitro activity with respect to cefaclor and the other cephalosporins as well as erythromycin and amoxicillin (the last one in BLP strains) . In the evaluation of the antibacterial activity of beta-lactam against Haemophilus and M . catarrhalis, the authors observed different indications in the guidelines for ampicillin . Cefixime is not destroyed by the plasmid-mediated beta-lactamase produced by Haemophilus sp . and M . catarrhalis (TEM and ROB in Haemophilus strains and BRO in M . catarrhalis) . In view of its excellent in vitro activity against the commonly encountered respiratory tract pathogens, cefixime is indicated in the therapy of these infections.

Chemotherapy, 1992, 38(1), 28 - 35
Antibacterial activity of cefixime against Streptococcus pneumoniae, Streptococcus pyogenes, and Haemophilus influenzae in the presence of Moraxella (Branhamella) catarrhalis; Yamada T et al.; We measured the sizes of the inhibition zones of oral beta-lactam antibiotics for Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae in the presence of beta-lactamase-producing-Moraxella (Branhamella) catarrhalis by the agar double-layer method . The sizes of the zones of amoxicillin for S . pneumoniae alone were the largest, followed in a descending order by those of cefixime and cefaclor . In the presence of 10(7) CFU/ml of M.(B.) catarrhalis, however, significant reduction of the sizes of the zones was seen with amoxicillin and cefaclor; inhibition with cefixime was nearly unchanged . Similar results were observed in those for S . pyogenes . These variable findings were attributed to the difference in stability of these drugs to the beta-lactamase produced by M.(B.) catarrhalis . When the susceptibility of H . influenzae in the presence of 10(8) CFU/ml of M.(B.) catarrhalis to cefixime, cefoteram, cefpodoxime, cefotiam and cefuroxime was examined, the sizes of the inhibition zones of all the drugs were reduced by the presence of 10(8) CFU/ml of M.(B.) catarrhalis, but those of cefixime were the largest of all the drugs tested . Our agar double-layer method is simple and useful for evaluating the influence of beta-lactamase-producing organism, as M.(B.) catarrhalis, on the disk susceptibility of other pathogens to antibiotics.

Vaccine, 1992, 10(7), 455 - 60
Controlled trial of Haemophilus influenzae type B diphtheria toxoid conjugate combined with diphtheria, tetanus and pertussis vaccines, in 18-month-old children, including comparison of arm versus thigh injection; Scheifele D et al.; A randomized, controlled comparison was made in 175 healthy 18-month-old children given either diphtheria and tetanus toxoids and pertussis vaccine, adsorbed (DTP) and haemophilus b diphtheria toxoid conjugate vaccine (PRP/D) concurrently at separate sites (66 children) or a new vaccine combining these products (109 children) . Rates of local or systemic adverse effects postimmunization and antibody responses to each component did not differ significantly between groups . DTP-containing vaccines were better tolerated when given in the thigh than in the arm . The combination DTP-PRP/D vaccine performed satisfactorily at 18 months of age, avoiding the inconvenience of two injections.

Photochem Photobiol, 1992 Jan, 55(1), 63 - 73
Photosensitization by 2-chloro-3,11-tridecadiene-5,7,9-triyn-1-ol: damage to erythrocyte membranes, Escherichia coli, and DNA; Kagan J et al.; The natural product 2-chloro-3,11-tridecadiene-5,7,9-triyn-1-ol (1) photosensitized the inactivation of Escherichia coli in the presence of near-ultraviolet light (320-400 nm; NUV) under both aerobic and anaerobic conditions . A series of E . coli strains differing in DNA repair capabilities and catalase proficiency exhibited indistinguishable inactivation kinetics following treatment with the chemical plus NUV . The presence of carotenoids did afford some protection to E . coli against inactivation under aerobic conditions, consistent with the involvement of singlet oxygen . The photosensitized hemolysis of human erythrocytes occurred more rapidly in the absence than in the presence of oxygen . Aerobically, the onset of hemolysis was partially inhibited by NaN3 and by 2,6-di-t-butyl-4-methylphenol (BHT) but not by superoxide dismutase (SOD) . The aerobic lipid peroxidation observed in the membranes of erythrocyte ghosts was completely inhibited by BHT, and partially by NaN3, but not by SOD . These results suggest that either lipid peroxidation of the membrane is not the main cause of photohemolysis or that BHT has insufficient access to intact erythrocyte lipids to protect them . Aerobically, crosslinking of membrane proteins was also observed; it was not affected by SOD, but was partially inhibited by BHT and NaN3 . The anaerobic photosensitized hemolysis of erythrocytes was more rapid; a radical mechanism was suggested since BHT inhibited the hemolysis to a greater extent than under aerobic conditions . Neither lipid peroxidation nor protein crosslinking was observed under conditions believed to be anaerobic . A light-dependent electron transfer to cytochrome c was obtained under argon but not under oxygen . Although induced mutations were not observed in the experiments with E . coli, 1 was capable of damaging both supercoiled pBR322 and Haemophilus influenzae transforming DNA in a manner that seemed to be equivalent under aerobic and anaerobic conditions . In conclusion, 1 can behave as typical photodynamic molecule under aerobic conditions but, in contrast to most photodynamic molecules, it is also phototoxic under anaerobic conditions . The extent to which the radical reactions detected under anaerobic reactions compete with the photodynamic processes when oxygen is present is not known.

Padiatr Padol, 1992, 27(2), A13 - A17
{Improvement in the mother-child health record in pediatric health care}; Hohenauer L; The recommended program of Child Health Care in Austria needs some additions: The first routine visit should be done between the 3rd and 5th week of life because of the insecurity of the young mother . The orthopedic examination must comprise the ultrasonographic examination of the hip . At 7-9 months of age the urinary screening for neuroblastoma must be incorporated into the existing program . The vaccination against haemophilus influenzae Type B must be added to the existing vaccination recommendations . During school age three additional examinations are recommended at 6, 10 and 15 years respectively.

Int J Pediatr Otorhinolaryngol, 1992 Jan, 23(1), 15 - 23
Effect of respiratory syncytial virus on adherence, colonization and immunity of non-typable Haemophilus influenzae: implications for otitis media; Patel J et al.; Adherence of non-typable Haemophilus influenzae to respiratory epithelium was evaluated in a cotton rat model of respiratory syncytial virus (RSV) infection . Colonization with non-typable H . influenzae increased to a maximum within 4 days of RSV infection compared to RSV negative controls (4.58 +/- 0.17 vs 3.82 +/- 0.23 log colony forming units (CFU) per ml, P less than 0.05) and then declined over the subsequent 10 days (2.0 +/- 0 vs 3.78 +/- 0.39 CFU per ml, P less than 0.0001) . In a second series of experiments, attachment of non-typable H . influenzae to epithelial cells collected from RSV infected cotton rats at the time of maximum virus replication was not different from controls (57.4 +/- 18.3 vs 52.0 +/- 24.3 bacteria per 50 cells) . Systemic immunity to non-typable H . influenzae as measured by IgG-specific antibody to the outer membrane complex and bactericidal antibody did not influence colonization . These data suggest that colonization with non-typable H . influenzae is significantly affected by a concurrent infection with RSV; however, the site of bacterial attachment is not known.

Int J Pediatr Otorhinolaryngol, 1992 Jan, 23(1), 1 - 13
Recurrent otitis media with non-typable Haemophilus influenzae: the role of serum bactericidal antibody; Bernstein JM et al.; The effect of serum bactericidal antibody on colonization with non-typable Haemophilus influenzae (NTHI) was studied in 26 children . Serum bactericidal antibody did not prevent colonization with NTHI in the nasopharynx . Antibody was present in 53% before, 91% during and 100% after documented colonization of the nasopharynx with NTHI . In addition, 5 children with recurrent otitis media with effusion (OME) due to NTHI were observed for bactericidal serum antibody during a 4-year period . Bactericidal antibody against the causative NTHI strain was not detected in the acute sera of any patient during each episode, but was observed in the convalescent sera of all of the patients . The bactericidal antibody in the convalescent serum did not appear to be protective against colonization and recurrence of disease by a different heterologous strain of NTHI . However, bactericidal antibody was augmented in some cases by a heterologous infection with NTHI . We confirmed the emergence of new strains of NTHI with DNA fingerprinting and outer membrane protein (OMP) analysis . The data suggest that the immune response to NTHI in OME is usually strain-specific, and furthermore, the results demonstrate that strain-specific bactericidal antibody does not prevent colonization in the nasopharynx with the homologous or heterologous bacterial strains . In general, bactericidal antibody is not cross-protective against heterologous strains of NTHI causing a second or third episode of otitis media with NTHI.

Dev Biol Stand, 1992, 74, 203 - 10
The effects of stopper drying on moisture levels of Haemophilus influenzae conjugate vaccine; Earle JP et al.; The discovery and development of increasingly potent biological and pharmaceutical products have resulted in very small amounts of the active ingredient in final product formulations . Pediatric vaccines with sub-milliliter dose sizes pose unique problems for final formulation and lyophilization, especially when stabilizers used are present in small amounts or are hygroscopic . Lyophilized Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate) (PedvaxHIB) has a plug weight of about 3 mg in its final formulation . Microgram amounts of water absorbed by the lyophilized plug can cause drastic changes in the moisture content of the product . In a small percentage of the final containers absorption of moisture by the vaccine may cause aesthetic defects (plug collapse) over time, or at elevated temperatures . This paper describes drying methods developed to control residual moisture levels in stoppers used as final container closures . Results on the moisture stability of the product capped with dried and non-dried stoppers are presented.

Dev Biol Stand, 1992, 74, 153 - 64
Measurement of final container residual moisture in freeze-dried biological products; May JC et al.; The Center for Biologics Evaluation and Research has changed its regulations pertaining to residual moisture in freeze-dried biological products as published in Title 21 of the Code of Federal Regulations for Food and Drugs . The new regulation requires that each lot of dried product be tested for residual moisture and meet and not exceed established limits as specified by an approved method on file in the product license application . The gravimetric or loss-on-drying method is no longer listed as the required method; the 1.0% moisture limit is no longer specifically stated in the regulation . These revisions were made to bring the regulation into line with changes in residual moisture testing methods and the results obtained when new testing methods were applied to the determination of residual moisture . This is illustrated with data for Measles Virus Vaccine Live and Haemophilus b Polysaccharide Vaccine using final container residual moisture test results obtained by the gravimetric, coulometric Karl Fischer, thermogravimetric and thermogravimetric/mass spectrometric methods . Guidelines for the determination of residual moisture in dried biological products have been issued to describe residual moisture test methods and procedures used to set product residual moisture limits . For most products levels of residual moisture should be low, usually from less than 1.0% to 3.0%, so that the viability, immunologic potency and therefore the stability of the product is not compromised over time.

Int J Clin Lab Res, 1992, 21(3), 231 - 4
Immunogenicity of Haemophilus influenzae type b capsular polysaccharide and its tetanus toxoid conjugate in patients with recurrent infections or humoral immunodeficiency; Barra A et al.; The antibody response to the capsular polysaccharide of Haemophilus influenzae type b was evaluated after vaccination with the capsular polysaccharide or its tetanus toxoid conjugate in 41 randomized patients with recurrent infections, IgA deficiency, common variable immunodeficiency, or the Wiskott-Aldrich syndrome . Serum antibodies were measured using a Farr assay for total antibodies and an enzyme-linked immunosorbent assay for antibodies of the three main immunoglobulin classes and of each IgG subclass . Antibody levels reached concentrations generally considered as protective in the majority of cases, the best response being observed after two injections of the conjugate vaccine with a 1-month interval . Vaccination with the conjugate therefore seems to be promising for the prevention of Haemophilus influenzae type b infections in such patients.

Antimicrob Agents Chemother, 1992 Jan, 36(1), 46 - 9
Comparative kill and growth rates determined with cefdinir and cefaclor and with Streptococcus pneumoniae and beta-lactamase-producing Haemophilus influenzae; Yourassowsky E et al.; The relationship between the growth rate and the kill rate was used to evaluate and to compare the in vitro bactericidal activities of cefdinir, a new oral cephalosporin, and cefaclor against Streptococcus pneumoniae and beta-lactamase-producing strains of Haemophilus influenzae . These frequently encountered pathogens of community-acquired respiratory tract infections are usually susceptible to both drugs . The MIC ranges for cefdinir and cefaclor were, respectively, 0.03 to 0.06 and 0.25 to 0.5 micrograms/ml for S . pneumoniae and 0.25 and 4 to 8 micrograms/ml for H . influenzae . The colony counts (CFU per milliliter) measured after 6 h of exposure to a range of antibiotic concentrations in broth were plotted against the colony count of the control culture over the same period of time . Higher kill rates versus bacterial growth rates were noted for S . pneumoniae for both drugs (positive balance) . Conversely, lower kill rates versus growth rates were noted for H . influenzae for both drugs (negative balance) . In conclusion, the bactericidal activities of both drugs against S . pneumoniae and H . influenzae were similar when expressed by the relationship between the growth rate and the kill rate at 6 h, but cefdinir was more active at lower concentrations.

Rev Mal Respir, 1992, 9 Suppl 1, R45 - 8
{Severe community-acquired pneumopathy . What initial antibiotics to use?}; Prud'homme A; Even if they represent only a minor percentage of all respiratory infections, acute pulmonary infections are the leading mortality cause from infectious diseases . Epidemiologic data amongst hospitalized patients with acute infections reveal mean mortality figures of 20% . The adequate assessment of severity criteria is fundamental so that patients can be oriented towards suitable hospitalized units . Risks factors to be considered are: other illnesses, age (greater than 60 years), breathing frequency greater than 30/min, diastolic blood pressure less than 60 mmHg, confusion, a PaO2 less than 60 Torr, a leukocytosis greater than 30,000 or less than 4,000/mm3, albuminemia less than 35 g/l and blood urea greater than 7 mmol/l . The association of these factors increases the risk of complications and mortality in a linear way . By contrast, the type of responsible organism is not relevant . Five microorganisms are responsible for 80 to 90% of documented acute pulmonary infections: pneumococci, Mycoplasma pneumoniae, Haemophilus influenzae, Legionella pneumophila, Myxovirus influenzae . However, direct examination of bacteriologic smear allows for a proper identification of the infectious agent in only 15% of cases . The clinician can therefore use epidemiologic, clinical and radiological findings to propose an oriented, though probable, antibiotic treatment . In these conditions, the initial treatment remains the association of an A type penicillin with an inhibitory effect on beta-lactamases and of a macrolide (or, eventually, of a fluoroquinolone) until results of bacteriologic investigations is known . No data is available to suggest the use of new third generation oral cephalosporins in the first intention treatment of acute severe pulmonary infections due to their low and inconsistent effect on pneumococcus.

ORL J Otorhinolaryngol Relat Spec, 1992, 54(1), 25 - 8
In vivo attachment of Streptococcus pneumoniae and Haemophilus influenzae to nasopharyngeal epithelium in children; Stenfors LE et al.; Attachment of Streptococcus pneumoniae and Haemophilus influenzae to epithelial cells on the posterior wall of the nasopharynx (NPH) was determined in 10 healthy children, culture-positive for either of these microorganisms . By using immunofluorescence technique and specific fluorescein-labelled antisera against these microorganisms, it was shown that in only 2 of the children studied were these pathogens firmly attached to the non-ciliated cells of the NPH . Attachment of S . pneumoniae and H . influenzae to the epithelial cells close to the nasopharyngeal opening of the Eustachian tube is of the utmost importance for the development of invasive disease, especially acute otitis media . Attachment of these pathogens to the epithelial cells covering the adenoid tissue may naturally be of significance for the induction of specific antibody body production against these microorganisms.

Rev Mal Respir, 1992, 9(2), 191 - 6
{Infectious agents associated with exacerbations of chronic obstructive bronchopneumopathies and asthma attacks}; Philit F et al.; Infections of the respiratory airways are frequently responsible for exacerbations of chronic obstructive pulmonary disease (COPD) and attacks of asthma . However, the causal infectious agents in practice are rarely precisely identified . We have undertaken a prospective study with the aim of researching into the bacteria and viruses associated with these exacerbations . Forty-seven patients who were in hospital between 1987 and 1989 for attacks of asthma (13 episodes) or exacerbations of COPD (35 episodes) were included in this study . The microbiological analysis consisted of: 1) the bacteriology of expectorated material or the products aspirated by fibroscopy with direct examination, quantitative cytology and culture; 2) samples taken from the nasal airways to identify and isolate pneumotropic viruses and mycoplasma; 3) serial serology looking for antibodies against pneumotropic bacteria and viruses . One of more infectious agents were shown in 47% of the episode studies of which 57% were exacerbations of COPD and treated 23% attacks of asthma . In the cases COPD bacteria were identified in 13 cases including Haemophilus influenzae {3}, Streptococcus pneumoniae {3}, Pseudomonas aeruginosa {3} . Amongst the 14 viruses recovered, the influenza virus {8} and the respiratory syncytial virus (VRS) {4} predominated . In 14 cases of acute asthma only 4 infectious agents were shown; Mycoplasma pneumoniae, influenza A, VRS and parainfluenza virus . The influenza virus was the agent most frequently discovered (26%) during the course of exacerbation of COPD and of asthma.

Sex Transm Dis, 1992 Jan-Feb, 19(1), 35 - 8
Molecular epidemiology, based on plasmid profiles, of Haemophilus ducreyi infections in the United States . Results of surveillance, 1981-1990; Sarafian SK et al.; To determine the distribution and extent of temporal changes in Haemophilus ducreyi strains in the United States, 342 isolates of H . ducreyi collected in 18 urban areas in the United States between 1981 and 1990 were characterized by plasmid content . Isolates possessed either no plasmid (29.8%), the 5.7-Mdal plasmid (50.9%), both the 4.4- and 5.7-Mdal plasmids (6.1%), the 3.2-Mdal plasmid (12.9%), or a combination of 1.8-, 2.6-, 2.8-, and 3.2-Mdal plasmids (1 case out of 342) . Isolates that possessed no plasmid or that possessed the 5.7-Mdal plasmid had the widest geographic distribution; only isolates from cities on the West Coast possessed the 3.2-Mdal plasmid . Evidence was found of temporal changes in H . ducreyi strain populations among isolates from both Tampa and New Orleans.

J Gen Microbiol, 1992 Jan, 138 ( Pt 1), 155 - 9
Immunogenic outer-membrane proteins of Haemophilus influenzae type b in infection; Langford PR et al.; Outer-membrane proteins (OMPs) from Haemophilus influenzae type b (strain Eagan), grown both in vitro (broth) and in vivo (rat intra-peritoneal), were separated by SDS-PAGE . The major OMPs were present in both growth conditions although the amounts of OMP a and OMP d were reduced in rat-grown organisms . There were strong additional bands in in-vivo-grown organisms at 51 and 92 kDa . Antiserum was raised in rabbits against in-vivo-grown bacteria, and absorbed with lysates of in-vitro-grown bacteria . This serum was used in Western blot analysis of OMPs from in-vitro- and in-vivo-grown cells to identify immunogenic proteins present in infection . These infection-associated OMPs had apparent molecular masses of 43 kDa, 48 kDa, 81 kDa and greater than 200 kDa . Bands of reactivity, of the same molecular mass as some of these, were found on immunoblots when rat and human convalescent sera were used as the source of primary antibody . In particular, a band of 81 kDa was recognized by pooled rat and three human convalescent sera.

Pediatr Infect Dis J, 1992 Jan, 11(1), 2 - 5
Persistent urinary antigen excretion in infants vaccinated with Haemophilus influenzae type b capsular polysaccharide conjugated with outer membrane protein from Neisseria meningitidis; Goepp JG et al.; Testing for urinary excretion of capsular polysaccharide antigen was carried out in 40 four-month-old Navajo infants who had received injections of a Haemophilus influenzae type b Neisseria meningitidis outer membrane protein conjugate vaccine (PedvaxHIB; Merck, Sharp and Dohme Research Laboratories) as part of an ongoing efficacy trial of the vaccine . Urine from 12 placebo recipients was also analyzed . Urine samples were collected on the day of injection (the first voided urine following the injection) and 3, 7, 10, 14, 21 and 30 days later . All vaccine recipients had at least 1 positive specimen . Vaccine recipients excreted antigen for a median period of 14 days after injection . On the first day 54% of vaccinees excreted antigen . Antigen was excreted by 89% of vaccinees on Day 3, 79% on Day 7, 82% on Day 10, 64% on Day 14, 56% on Day 21 and 41% on Day 30 . Urine from placebo recipients tested positive in 12% on Day 1, 18% on Day 3, none on Day 7, 14% on Day 10, 11% on Day 14, 10% on Day 21 and none on Day 30 . The rate of positive test results was significantly higher among vaccine recipients than among controls . Physicians should not rely on urinary antigen detection tests for predicting the presence of invasive disease caused by H . influenzae type b in infants for at least 30 days after injections with this conjugate vaccine, and possibly longer.

J Infect, 1992 Jan, 24(1), 37 - 42
The spectrum of chest infections in HIV positive patients in Edinburgh; Willocks L et al.; In a retrospective analysis of all known HIV-positive patients admitted to the City Hospital before November 1989, 208 patients accounted for 612 admissions, 72% being injection drug users (IDUs) . One hundred and eighty admissions (29%) were for chest-related disorders, and this was the commonest reason for admission . Unlike other U.K . centres where more than 50% chest problems are due to Pneumocystis carinii pneumonia (PCP), only 27% of our chest admissions were for PCP . Fifty-four percent of chest admissions were for bacterial chest infections (BCIs), the commonest organism isolated being Haemophilus influenzae . Despite the fact that most (50/97) of these admissions were in patients with 'asymptomatic' HIV disease (CDC classification 2 and 3), 50% had radiological pneumonia, 43% were hypoxic, 28% were hypercapnic and the average duration of hospitalisation was 10 days . BCIs were more common in HIV-positive IDUs when compared with HIV-negative IDUs, other HIV-positive patients and the general age-matched population . Medical provision for IDU-related HIV disease should take into account the high rate of BCIs and of hospital admissions in patients who do not yet have CDC stage 4 disease.

Diagn Microbiol Infect Dis, 1992 Jan, 15(1), 39 - 53
Clarithromycin, a unique macrolide . A pharmacokinetic, microbiological, and clinical overview; Hardy DJ et al.; The in vitro and in vivo spectrum of antibacterial activity of clarithromycin is summarized and related to its human pharmacokinetics . In vitro studies by several investigators have documented clarithromycin's activity against bacterial agents of respiratory tract infections, skin and soft tissue infections, and sexually transmitted diseases . Clinical cure rates of 52%-83% (pneumonia), 79%-96% (bronchitis), 82%-96% (pharyngitis), 58% (sinusitis), and 78% (skin/skin-structure infections) have been reported in patients receiving clarithromycin in comparative trials . Respective bacteriologic eradication rates in clarithromycin recipients have been reported as 57%-89%, 79%-96%, 88%-100%, 89%, and 90% . In vitro and in vivo studies suggest that clarithromycin, when combined with its major human metabolite, 14-hydroxyclarithromycin, is also effective against Haemophilus influenzae . A New Drug Application claiming efficacy in the treatment of lower respiratory tract infection, sinusitis, pharyngitis, and skin and skin-structure infections caused by susceptible pathogens has been filed with the Food and Drug Administration (FDA) . This review summarizes relevant pharmacokinetic, microbiological, and clinical data for clarithromycin.

Infection, 1992, 20 Suppl 1, S58 - 60
Changes in lymphocyte subpopulations in patients treated with cefodizime for acute lower respiratory tract infections; Valcke Y et al.; The influence of cefodizime (CDZ) on CD4 and CD8 lymphocytes was investigated in patients with lower respiratory tract infection and underlying respiratory diseases . Ten men and one woman were treated with CDZ 1 g i.m . b.i.d . for ten days . The infecting organisms were Haemophilus influenzae (5), Streptococcus pneumoniae (2) and Escherichia coli (1) . No adverse events were reported . Nine patients were clinically cured; two required further antibiotic therapy . Leucocyte counts decreased significantly during treatment . Lymphocyte counts and CD4 cells both increased significantly in absolute and relative numbers, while there was a much smaller increase in CD8 cells . This resulted in a significant increase in the CD4/CD8 ratio . These effects of CDZ might be of benefit for immunocompromised patients with bacterial infections.

Infection, 1992, 20 Suppl 1, S26 - 30
Review of effectiveness of cefodizime in the treatment of lower respiratory tract infections with parenchymal involvement; Pauwels RA; The efficacy of cefodizime (CDZ) in lower respiratory tract infections (LRTI) with parenchymal involvement was assessed by the analysis of data from 919 patients who participated in four controlled, randomized studies and three open studies . Sputum bacteriology and a chest x-ray were performed at baseline and after therapy . A total of 778 patients were evaluable for clinical efficacy and 451 for bacteriological efficacy . The most frequent pathogen was Streptococcus pneumoniae, followed by Staphylococcus aureus, Klebsiella pneumoniae and Haemophilus influenzae . CDZ 1 g b.i.d., 2 g b.i.d . and 2 g once daily achieved clinical and bacteriological cure rates above 90%, which matched those observed with the comparators (cefuroxime 1.5 g t.i.d . and cefotaxime 2 g b.i.d.) . No significant differences in clinical and bacteriological outcome were detected when the various CDZ dosage regimens were compared . 1 g CDZ b.i.d . is therefore recommended as the regimen of choice for the treatment of LRTI with parenchymal involvement, with CDZ 2 g once daily as an alternative.

Infection, 1992, 20 Suppl 1, S22 - 5
Clinical and bacteriological experience with cefodizime in acute purulent exacerbations of chronic bronchitis; Davies BI et al.; 1 or 2 g doses of cefodizime i.m . were studied in 287 patients admitted to hospital with acute purulent exacerbations of chronic bronchitis, mostly associated with Haemophilus influenzae, Streptococcus pneumoniae or Moraxella catarrhalis . Pharmacokinetic studies in serum and sputum on the first treatment day yielded mean peak serum concentrations of 50 to 100 mg/l, with corresponding sputum concentrations of 1.4 and 2.7 mg/l, after the two respective doses . No great differences were found between the clinical and microbiological results in the various dosage groups, and no corresponding improvement was noted with the highest dosages studied . In general, infection was eliminated in 90 to 95% of patients at the end of treatment, and in approximately 70 to 80% after a follow-up week . Some infections associated with beta-lactamase producing M . catarrhalis persisted or relapsed after treatment . Unwanted drug effects were recorded in five patients, leading to discontinuation in two . It is concluded that a single daily intramuscular dose of 1 g cefodizime for seven days produces satisfactory results in most patients.

Vaccine, 1992, 10(9), 627 - 30
Immunity to Haemophilus influenzae type b on sample population from central Italy; Sansoni A et al.; A study on natural immunity to Haemophilus influenzae type b (Hib) was carried out in the province of Siena on 474 subjects ranging in age from 3 days to 70 years . The titration of antibody to capsular polysaccharide (PRP) was performed by the radioantigen-binding assay (RABA) method . A total of 66.67% of the population studied presented an antibody level considered to be protective (greater than or equal to 0.15 microgram ml-1) . Seropositivity was 5.7% in the 5-7 month age group and 29.09% in the 8-17 month age group . This rose progressively in successive age groups reaching 79.54% between 4 and 6 years old and a value greater than 90% after 7 years old . From 3 to 17 months even the geometric mean of antibodies to PRP was below the protective limit . Our data indicate that, even in Italy, the majority of the infant population is not protected against H . influenzae, and therefore that vaccination should also be introduced in this country.

Enferm Infecc Microbiol Clin, 1992 Jan, 10(1), 34 - 8
{Bacteriology of mucoviscidosis during a 5-year period}; Ferrer A et al.; BACKGROUND: We have studied the bacteriology of mucoviscidosis cases from 1985 to 1989 . MATERIAL: A total of 336 samples from 50 patients (median age: 7 year, range: 1 day-18 years) with mucoviscidosis were studied . RESULTS: The most frequently isolated microorganisms was Pseudomonas aeruginosa (59.2%), followed by Staphylococcus aureus (19%) and Haemophilus influenzae (18.4%) . In patients younger than 1 year of age other different microorganisms were identified in 61.1% of cases, but S . aureus (11.1%) and Pseudomonas aeruginosa (5.5%) were also isolated . The incidence of Pseudomonas cepacia (0.6%) is low in our environment . We did not isolate any Legionella sp . strain.

Jpn J Antibiot, 1992 Jan, 45(1), 74 - 86
{Pharmacokinetics and clinical effects of cefdinir 10% fine granules in pediatrics}; Motohiro T et al.; Cefdinir (CFDN), a newly developed oral cephalosporin in a 10% fine granular form, was administered to 8 children and concentrations of the drug in plasma and urine and urinary recovery rates of the drug were determined . The subjects were divided into 2 groups of 4 children each; one group received 3 mg/kg of CFDN at 1 hour before meal (in the fasting state), and the other, at 30 minutes after meal . To study clinical and bacteriological effects of this drug, a mean dose of 4.8 mg/kg t.i.d . was administered for 8 days on the average to 9 children with various infections; tonsillitis (3 cases), acute bronchitis (1), pneumonia (1), acute purulent otitis media (1), urinary tract infection (2), and impetigo (1) . MICs were determined for 6 drugs including CFDN, cefaclor, cefixime (CFIX), methicillin, cloxacillin, amoxicillin (AMPC) against 4 strains freshly isolated from children receiving CFDN . An inoculum size of 10(6) cfu/ml was used in the MIC-determinations . Adverse reactions and abnormal laboratory findings attributable to this drug were also examined in these children . The results obtained are summarized as follows . 1 . Mean plasma peak levels of CFDN were observed at 2 hours after administration in the before-meal group and 4 or 5 hours after administration in the after-meal group mean peak values of 0.88 and 0.50 micrograms/ml, respectively . Mean half-lives were 1.61 hours in the before-meal group and 2.54 hours in the after-meal group, and mean AUCs were 4.24 in the former and 3.59 micrograms.hr/ml in the latter . 2 . Mean urinary peak concentrations of CFDN were observed during 2-4 hours after dosing in the before-meal group and during 6-8 hours in the after-meal group with values of 93.3 and 44.8 micrograms/ml, respectively, in cases for which plasma concentrations of drugs were determined . Mean urinary recovery rates during the first 8 hours after administration in the before- and after-meal groups were 16.6 and 13.4%, respectively . 3 . Good clinical effects were obtained with an efficacy rate of 100% in 9 patients with 6 diseases due to bacterial infections . 4 . Good bacteriological effects were also obtained against 2 strains of Streptococcus pyogenes, 2 strains of Escherichia coli and 1 strain of Haemophilus influenzae with an eradication rate of 100% . In 3 cases of these and another case (normal flora), strains present before the study were replaced by other strains.(ABSTRACT TRUNCATED AT 400 WORDS)

Jpn J Antibiot, 1992 Jan, 45(1), 48 - 73
{Bacteriological, pharmacokinetic and clinical studies of 5% and 10% granules of cefdinir in the pediatric field}; Toyonaga Y et al.; Bacteriological, pharmacokinetic and clinical studies on cefdinir (CFDN, FK482), a new oral cephalosporin, 5% and 10% granules, were performed in the field of pediatrics . The results are summarized below . 1 . Antibacterial activities Antibacterial activities of CFDN against Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, Branhamella catarrhalis, Escherichia coli and Klebsiella pneumoniae were studied in comparison with those of cefaclor (CCL), cefixime (CFIX) and amoxicillin (AMPC) . MIC80's of CFDN against S . aureus, S . pneumoniae, S . pyogenes, H . influenzae, B . catarrhalis, K . pneumoniae and E . coli were 0.78, 0.20, less than or equal to 0.025, 0.39, 0.10, 0.20 and 0.10 micrograms/ml, respectively . These results show that CFDN has high antibacterial activities against these organisms . MIC80's of CFDN against Gram-positive bacteria were similar to those of AMPC, and was lower than those of CCL and CFIX . As for antibacterial activities against Gram-negative bacteria (GNB), the MIC80 of CFIX against H . influenzae was 0.05 micrograms/ml, which was slightly lower than that of CFDN . THe MIC80's of CFDN against other GNB were similar to those of CFIX . 2 . Absorption and excretion Blood concentrations and urinary excretion rates of CFDN 5% and 10% granules and 100 mg capsule were determined . The data on CFDN 10% granules were similar to those on CFDN 5% granules . At a dose of 3 mg/kg, peak blood concentrations (Cmax's) of CFDN ranged from 0.20 to 2.12 micrograms/ml with 5% granules and from 0.50 to 1.15 micrograms/ml with 10% granules at 2 to 3 hours after dosing . At a dose of 6 mg/kg, peak concentrations were 0.66-2.06 micrograms/ml and 0.70-1.52 micrograms/ml with 5% granules and with 10% granules, respectively . At 8 hours after dosing, blood concentrations were 0.04-0.54 micrograms/ml at 3 mg/kg and 0.06-0.27 micrograms/ml at 6 mg/kg . Blood half-lives were 1.33-4.36 hours at 3 mg/kg and 1.14-3.27 hours at 6 mg/kg . AUC's were 1.7-11.0 micrograms.hr/ml with 3 mg/kg and 2.4-8.7 micrograms.hr/ml with 6 mg/kg . With administration of single 100 mg capsule, Cmax's, blood concentrations after 8 hours, T1/2's and AUC's were 0.79-1.88 micrograms/ml, 0.20 micrograms/ml, 1.54-2.72 hours, and 5.2 micrograms.hr/ml, respectively . Urinary recovery rates in the first 8 hours ranged from 6.85 to 39.2% with 3 mg/kg and 6.08-25.5% with 6 mg/kg.(ABSTRACT TRUNCATED AT 400 WORDS)

Beitr Gerichtl Med, 1992, 50, 205 - 9
{Unexpected fatalities in childhood caused by acute epiglottitis}; Nadjem H et al.; Report on two deaths from a natural internal cause in children beyond the first year of life . The children (a two-year and a three-year old boy), who seemed completely healthy, sudden suffered from acute inflammation of the upper respiratory tract with dyspnea, inspiratory stridor, fever, dysphagia, and flow of saliva . The disease took a fulminant course and the children died within a few hours showing symptoms of intense dyspnea and cyanosis . The above symptoms and progress were typical of acute epiglottitis . Autopsy revealed an intense inflammation and tumescence of the epiglottis in both cases . The diagnosis of epiglottitis was confirmed histologically and bacteriologically (Haemophilus influenzae).

Int Rev Immunol, 1992, 9(1), 57 - 78
Human antibody responses to bacterial antigens: studies of a model conventional antigen and a proposed model B cell superantigen; Silverman GJ; We have investigated the human antibody repertoires that bind to two different classes of bacterial antigens . Immunization with the conventional antigen, type b capsular polysaccharide of Haemophilus influenzae Hib PS, uniformly induces IgA and IgG responses dominated by clones that use heavy chains structurally related to two subsets of VH3 genes, while in a minority of subjects antibodies from the VH1 or VH4 families are co-induced . In contrast, the "alternative binding site" of Staphylococcal Protein A (SPA) represents an unconventional determinant, because; (i) SPA is bound by a large proportion of non-immune IgM, IgA and IgG F(ab')2, (ii) SPA is bound only to Fab from the VH3 family, which can be encoded by at least four different germline genes, (iii) SPA binding is independent of VL usage, (iv) by flow cytometry SPA is bound by > 15% of tonsilar B cells, but not to T cells . (v) In vitro stimulation with an SPA containing mitogen induces the preferentially production of Ig bearing a VH3 marker . Taken together, these studies characterize a VH family restricted binding interaction that is distinct from the properties associated with conventional antigens such as Hib PS . Based on these data we propose that SPA represents a prototype for a B cell superantigen.

Int Rev Immunol, 1992, 9(1), 25 - 43
The repertoire of human antibody to the Haemophilus influenzae type b capsular polysaccharide; Insel RA et al.; Human antibody to the Haemophilus influenzae capsular polysaccharide (Hib CP) is restricted in diversity in the individual and the population with a limited number of variable region genes encoding antibody . Antibody to the Hib CP shows restricted isoelectric focusing gel patterns and light chain usage with frequent restriction to use of only kappa light chains . Shared cross-reactive idiotypes are expressed on antibody . The heavy chain of antibody to the Hib CP is predominantly encoded by two members of the VH3 family--LSG 6.1/M85-like and VH26/30P1-like . In VH the CDR1, based on complete identity in LSG 6.1/M85-like antibodies, CDR2, based on the suggestion of mutation in this region, and CDR3, based on conserved CDR3 usage in unrelated individuals, may be important for antigen binding . Six or more different VL gene families encode antibody . The predominant antibody of the majority of individuals uses the A2-V kappa II gene in germline or near germline configuration, which encodes an idiotype designated HibId-1 . Antibody can also be encoded by V kappa I, non-A2 V kappa II, V kappa III, V kappa IV, V lambda II, and V lambda VII genes . Although different VL genes can be used, unrelated individuals appear to use the same V kappa III (A27), V lambda II (V lambda 2.1 and V lambda VII (4A) genes . The VL diversity accounts for differences in fine binding specificity, with A2-V kappa II genes not encoding E . coli K100 CP cross-reactive antibodies and V lambda VII genes and some of the non-A2 V kappa genes encoding cross-reactive antibodies . The arginine in CDR3 of both antibody kappa and lambda light chains and the asparagine in CDR2 of VL sequences and in CDR1 of LSG6.1-M85 VH sequences of antibody appear to be important residues for antigen binding . A relatively limited degree of somatic mutation has occurred in the non-A2 VL genes, V lambda VII, and the VH genes . Further studies comparing the polymorphism of germline V genes to antibody-encoding V genes are needed to clarify this issue . Research comparing this repertoire to repertoires directed to other bacterial CP and to self antigens and defining structure-antigen binding relationships is in progress.

Pharmacotherapy, 1992, 12(6 Pt 2), 94S - 103S
Recent developments in vaccines and immunization practices; Casto DT; Dramatic changes have been made in the recommended schedule for immunizations, and for a variety of reasons: greater understanding of risks associated with whole-cell pertussis vaccine; introduction of more immunogenic vaccines to prevent invasive disease caused by Haemophilus influenzae type B; a national epidemic of measles that affected many vaccinated individuals; and the failure of targeted use of vaccine in high-risk patients to reduce the occurrence of hepatitis B . Additional changes in recommended regimens can be anticipated as new products are introduced . However, for vaccines to have their greatest impact, improved adherence to recommended immunization practices is necessary.

Pharmacotherapy, 1992, 12(6 Pt 2), 86S - 93S
Problems and dilemmas of antimicrobial resistance; Murray BE; An important obstacle to the long-term efficacy of an antimicrobial agent is the appearance and spread of resistance to the agent . The fact that many antimicrobials are produced by microorganisms in nature may provide long-term selective pressure for the emergence of resistance in antibiotic-producing as well as -nonproducing organisms . Indeed, the rapidity with which many resistances have appeared after the introduction of a new antibiotic suggests that these resistance genes were already present somewhere in nature prior to clinical use . In the hospital setting, the most recent worrisome resistance traits to emerge include plasmid-mediated resistance to imipenem and to third-generation cephalosporins among nosocomial gram-negative bacteria, and the acquisition of resistance to vancomycin by enterococci . Methicillin-resistant staphylococci continue to be a problem and are increasingly resistant to numerous other agents such as rifampin and the newer fluoroquinolones . The most important resistances seen in community-acquired organisms include beta-lactam resistance in pneumococci and combined ampicillin and chloramphenicol resistance in Haemophilus influenzae . Shigellae resistant to essentially all commonly used oral agents are also a problem, particularly in developing countries . No end is in sight to the problem of antimicrobial resistance, and thus new strategies to prevent infections and control resistant organisms continue to be necessary.

Drugs Exp Clin Res, 1992, 18(6), 225 - 31
The sensitivity of clinical bacteria isolated in Scotland to the oral cephalosporin, cefdinir; Payne DJ et al.; The minimum inhibitory concentration (MIC) of cefdinir (CI-983, FK-482), cephalexin cefuroxime, cefixime and ceftazidime were determined against clinical isolates . Cefdinir was as effective as cefixime against Haemophilus and Moraxella (Branhamella) strains and both were more effective than cefuroxime . Against streptococci, cefdinir was much more effective than cefixime and had similar efficacy to cefuroxime . Against staphylococci, cefdinir had the lowest MIC50 of all of the drugs tested . The efficacy of these antibiotics was tested against Escherichia coli K12 strains harbouring 16 of the new extended-spectrum plasmid-mediated beta-lactamases, and cefdinir was more effective than ampicillin, cephalexin, cefuroxime, ceftazidime and aztreonam.

Zh Mikrobiol Epidemiol Immunobiol, 1992, (7-8), 14 - 7
{The etiological structure of acute bacterial meningitis in different regions}; Kostiukova NN et al.; In 1985-1989 the etiological structure of acute bacterial meningitides (ABM) in children was studied in 4 largest industrial cities in different regions of the European part of the former USSR, as well as in 2 industrial cities of western Siberia . Due to the common methodological approach used in all investigations, comparable data were obtained in all cities . These investigations revealed that meningococci caused 53.0-86.7% of all cases of ABM in children, which corresponded to moderately increased morbidity rate in meningococcal infection (3.9-11.0 cases per 100,000 of the population, mostly 5.0-7.0 cases) in these cities with its progressive decrease during 3-4 years of observation . The gradual change of meningococci from group A, prevailing in the '70s and early '80s, to group B and in some cases the appearance of group C meningococci, accompanied by a decrease in morbidity rate, were noted . In St . Petersburg the indices of ABM morbidity in children aged up to 5 years for 1987 and 1988, caused by Haemophilus influenzae (0.74 and 4.13) and pneumococci (3.23 and 4.86), could be calculated . A great number of ABM cases of unclear etiology (15.9-33.3%) suggests that the number of ABM cases caused by these two infective agents was underestimated.

Scand J Infect Dis, 1992, 24(5), 629 - 32
Antibody response to a Haemophilus influenzae type b polysaccharide tetanus toxoid conjugate vaccine in splenectomized children and adolescents; Kristensen K; 20 children and adolescents 4-18 years old and splenectomized for various reasons (spherocytosis (n = 6), idiopathic thrombocytopenia (n = 8), other (n = 6)) were immunized once with a Haemophilus influenzae type b (Hib) polysaccharide tetanus toxoid conjugate vaccine . Prior to vaccination 10/20 patients had anticapsular antibodies below what could be considered the minimum protective level in splenectomized (0.6 micrograms/ml), whereas all obtained high antibody levels after vaccination . In addition 1 infant with congenital asplenia was vaccinated at 2,4 and 6 months of age, and was shown to respond well after the second and third injection with serum antibody concentrations of 0.84 and 10.7 micrograms/ml respectively . Because asplenic individuals have an increased risk of invasive Hib infection, these data suggest that vaccination of such individuals against Hib may be justified.

Probl Tuberk, 1992, (9-10), 41 - 4
{Pneumotropic microorganisms in chronic diseases of the respiratory organs and tuberculosis of the lungs}; Selina LG; Species composition and the etiologic role of S . pneumoniae and of bacteria of Haemophilus genus in origination and maintenance of diverse lung pathology were specified and the problem of their carriage in pulmonary tuberculosis patients in the absence of nonspecific infection was investigated . The results of study have confirmed that S . pneumoniae was and still remains one of the most common pathogens of chronic respiratory diseases (55.8% of bacteria was found in sputum and 64.7% in bronchoalveolar lavage and exudate) . Serological verification of microorganisms isolated from the sputum by the indirect immunofluorescence method was obtained in 77.4% of the studies . Bacteria of Haemophilus genus were more often isolated together with pneumococcus (15.4%) and were verified serologically in only 31.8% of the cases . Transitory (asymptomatic) carriage was found in 412 pulmonary tuberculosis patients . S . pneumoniae accounted for 62% and Haemophilus for 20%.

Probl Tuberk, 1992, (9-10), 21 - 3
{The potentialities and results of the etiologic diagnosis of acute pneumonias}; Andreeva OV et al.; The paper deals with the results of the joint Soviet-Hungarian study for the determination of etiology of acute pneumonias . Study included 617 patients . The bacteriologic and serologic methods were used to reveal the causative agent of the disease . Prevalence of Streptococcus pneumoniae (33-49%) in the etiologic structure of acute pneumonias was established both in the USSR and Hungary . In many cases pneumonia is also caused by Haemophilus influenzae (21-22%) . In 15-31% of the cases the causative agent of pneumonia is gram-negative microorganisms . A protracted course of acute pneumonia is due to the complex associations of microorganisms including S . pneumoniae . A conclusion has been drawn to the effect that the initial antibacterial therapy should be started with administration of antibiotics that act effectively on S . pneumoniae.

Nord Med, 1992, 107(11), 278 - 9
{Bacterial adhesion to epithelial cells of the nasopharynx essential in the development of otitis media}; Stenfors LE et al.; Otitis media develops when certain bacterial pathogens gain access to the middle ear cavity from the nasopharynx through the eustachian tube . Adhesion of bacteria, in particular Streptococcus pneumoniae and Haemophilus influenzae, to the non-ciliated epithelial cells of the nasopharynx, close to the opening of the eustachian tube, is significantly correlated to the otitis-prone condition in children . Otitis-prone children have significantly fewer bacteria in the nasopharynx coated with the immunoglobulin secretory IgA (SigA) then healthy children have . Adhesion and occurrence of middle ear pathogens in the nasopharynx decreases with advancing age . Epstein-Barr virus, causative agent of infectious mononucleosis, causes a remarkable increase in bacterial adhesion to epithelial cells.

Acta Otolaryngol, 1992, 112(3), 524 - 9
Permeability of the normal round window membrane to Haemophilus influenzae type b endotoxin; Lundman L et al.; Sensorineural hearing loss associated with otitis media may be due to passage of ototoxic substances such as bacterial toxins and antibiotics, from the middle ear into the inner ear . The round window membrane is the most likely route for such transport . The aim of this study was to analyze the extent of endotoxin passage through the normal round window membrane . The round window membranes of 19 chinchillas were exposed in vivo to Gelfoam soaked in purified Haemophilus influenzae type b endotoxin at a concentration of 45,000 endotoxin units per ml (EU/ml) during 3 to 24 h . Endotoxin levels in the perilymph were measured with Limulus Amaebocyte Lysate or Quantitative Chromogenic Limulus Amaebocyte Lysate . Endotoxin was detected in half of the inner ears at concentrations close to the detection limit (approximately 4 EU/ml) . The results suggest that the normal round window membrane efficiently protects the inner ear against the passage of bacterial endotoxins from the middle ear cavity . It is unlikely that endotoxin at concentrations found in the middle ear secretion during otitis media can traverse the round window membrane in sufficient amount to cause inner ear deterioration.

Rev Pneumol Clin, 1992, 48(3), 95 - 100
{Models of experimental Haemophilus influenzae and Streptococcus pneumoniae pneumonia in mice}; Bedos JP et al.; Streptococcus pneumoniae and Haemophilus influenzae are the bacteria most frequently involved in bronchopulmonary and E.N.T . diseases . Experimental models are useful to analyse in vivo the physiopathological interactions between bacteria and lung tissue and to study the activity of various antibiotics in the focus of infection . Models for pneumococci are devised according to the virulence of the strain, the inoculation technique and the type of animal used . When strains of different virulence and hosts of different lineage are combined, several experimental models with different natural histories are obtained . These experimental models make it possible to study therapeutic measures at different stages, comparing the relative activities of fluoroquinolones, ampicillin and macrolides . For fluoroquinolones, no correlation has been found between in vivo and in vitro data in these models, but the effectiveness of new compounds has been studied . As regard Haemophilus influenzae, lung infection models are rare, either because their septicaemic component is too important or because they do not enable this organism to multiply . Moreover, the models obtained do not lend themselves easily to therapeutic trials and favour those antibiotics that have high serum concentrations . Developing a better model would enable us to improve our knowledge of the pathogenicity of this micro-organism.

Rev Pneumol Clin, 1992, 48(3), 101 - 10
{Epidemiology of micro-organisms responsible for community-acquired pneumonia}; Mayaud C et al.; Pneumonias occupy a prominent situation among lower respiratory tract infections where they are remarkable for their potential mortality and for our relative knowledge of the responsible micro-organisms . Analysis and synthesis of each series published must answer several questions, such as: what are the lung diseases considered? which investigations have been performed? which criteria of imputability have been used? in which patients has the study been carried out? in which place, which period and which structure? In spite of methodological lacunae and of the inhomogeneous answers to the questions asked, there is some concordance between the series found in the literature . Thus, more than 90% of community-acquired pneumonias with microbiological identification are caused by Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Legionella pneumophila, Chlamydia psittaci (or pneumoniae), or Influenza A virus.

Auris Nasus Larynx, 1992, 19(2), 69 - 74
Adherence of Haemophilus influenzae to middle ear mucosa injured by killed H . influenzae; Hando S et al.; Repetitive acute otitis media is due to recurrent bacterial infection of middle ear superimposed on chronic otitis media with effusion . Endotoxin, one of the constituents of Haemophilus influenzae, is present in some cases in the middle ear effusion of otitis media with effusion and has been demonstrated experimentally to damage the middle ear mucosa . The aim of this study was to determine the effect of killed H . influenzae on the adherence of H . influenzae and H . parainfluenzae to the middle ear epithelial cells . The numbers of adherent organisms per epithelial cell in ears inoculated previously with killed H . influenzae or with normal saline (0.9% NaCl) were compared . Prior middle ear inoculation of killed H . influenzae enhanced the adherence of H . influenzae to middle ear epithelial cells, but it had little effect on the adherence of H . parainfluenzae . H . influenzae adhered to middle ear epithelial cells in greater numbers than H . parainfluenzae . Results demonstrate that a middle ear pathogen adheres to middle ear epithelial cells presumably damaged by killed H . influenzae, whereas a non-pathogen does not . These findings might partly explain the increased susceptibility of an ear with chronic otitis media with effusion to recurrent infection with H . influenzae.

Scand J Infect Dis, 1992, 24(4), 485 - 93
Antibiotic susceptibility of upper respiratory tract pathogens in Sweden: a seven year follow-up study including loracarbef . Swedish Respiratory Tract Study Group; Olsson-Liljequist B et al.; The antibiotic susceptibility of Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes and Streptococcus pneumoniae was investigated in five different geographical areas of Sweden in 1990 and compared with results from similar investigations performed in 1983 and 1986 . Tests on 100 isolates per species and laboratory were performed by the disk diffusion method, and 10% of the strains plus all resistant ones were sent to the central laboratory for determination of MICs of ampicillin, phenoxymethylpenicillin, cefaclor, loracarbef, erythromycin, tetracycline and trimethoprim/sulfamethoxazole . Beta-lactamase production was found in 7% of H . influenzae and 71% of M . catarrhalis, and reduced susceptibility to penicillin in 3% of S . pneumoniae . Low frequencies (1-3%) of tetracycline resistance were found in H . influenzae and in the 2 streptococcal species, in which also less than 1% of the strains were resistant to erythromycin . Resistance to trimethoprim/sulfamethoxazole occurred in 7% (range 3-14%) of H . influenzae and in 3% of S . pneumoniae . Cefaclor was active against all streptococci except against S . pneumoniae with reduced susceptibility to penicillin . It was active against beta-lactamase negative strains of M . catarrhalis but had, according to the SIR-system, intermediate activity against H . influenzae . Loracarbef was twice as active as cefaclor against H . influenzae but equally active against the 3 other species tested.

Sb Ved Pr Lek Fak Karlovy Univerzity Hradci Kralove, 1992, 35(1), 5 - 40
On the relationship between theoretical presumptions asbestos genotoxicity and the practical monitoring of exposed workers; Srb V; From the genotoxic viewpoint, there exists a sufficient evidence for asbestos carcinogenicity to human population and animals . Asbestos is a solid cancer promoter (cocarcinogen) of non-mutagenic character having epigenetic effects (15, 16) . No data have been published on its mutagenic activity in "in vivo" conditions in man . The only results are those of our pilot study carried out in the period of 1981-1983, which cast doubts on the official view of non-mutagenic character of asbestos--at least under occupational conditions of its processing (34, 36, 37) . The study presented here represents ten years' efforts made in the biological (cytogenetic) monitoring of persons occupationally exposed to asbestos in a factory for its processing (occupational risk) . Simultaneously, a preliminary answer is given to the question whether the Osinek factory (situated in a housing area) is or is not dangerous for inhabitants of the town of Kostelec nad Orlici, namely for their genetic apparatus (environmental risk) . Using the method of chromosome aberrations analysis in peripheral blood lymphocytes, a total of 431 subjects (245 males and 186 females) were examined in the period of 1981 to 1988 . Of these, 111 persons were from control workplaces (from Osinek or--starting from 1984--from other plants in Kostelec nad Orlici; in addition to that 14 pensioners without any occupational exposure were examined) . The average age of workers exposed to asbestos risk was 42.7 years, in the controls it was 43.9 years, in pensioners exposed to asbestos earlier 63.5 years and in those never exposed to asbestos 66.5 years . The average number of years spent at Osinek factory amounted to 21.5 years . About one third of employees were found to suffer from allergies (first of all those of air passages) and one sixth from chronic ailments of the upper air passages (Staphylococcus aureus, Haemophilus influenzae and Streptococcus beta-haemolyticus were diagnosed most frequently) . A third part of workers from high-risk workshops are smokers, only a fourth of the controls . About 40% of workers regularly consume alcoholic drinks . The average morbidity rate at Osinek in 1981 to 1988 was 6.3% (in workers as high as 9%), which is about 2% higher as compared with mean values obtained in the district of Rychnov nad Kneznou and East-Bohemian region . Within the nine-year period (1981-1989), 21 occupational diseases were diagnosed, while in the previous 24 years there were 24 cases of an occupational disease . Earlier they were mainly asbestoses (87%), in the last period mainly cancer diseases coinciding with asbestosis (81%).(ABSTRACT TRUNCATED AT 400 WORDS)

J Gen Microbiol, 1992 Jan, 138 ( Pt 1), 161 - 8
Localization of conserved B-cell epitopes among encapsulated and non-encapsulated Haemophilus influenzae P2 porin proteins using synthetic peptides; Hamel J et al.; The P2 outer membrane protein of Haemophilus influenzae belongs to a class of apparently ubiquitous proteins in Gram-negative bacteria that function as porins . Murine hybridomas raised to the P2 protein and synthetic peptides were used to investigate the structural and antigenic relationships among P2 proteins of encapsulated and non-encapsulated H . influenzae . Three monoclonal antibodies (mAbs), P2-17, P2-18 and P2-19, recognizing epitopes on the P2 protein, as shown by Western immunoblotting of outer membrane preparations, and purified and recombinant P2 proteins are described . The epitopes reactive with the mAbs were widely distributed among H . influenzae strains since 70-100% of strains of encapsulated and non-encapsulated isolates collected worldwide were recognized by individual mAbs . None of the mAbs reacted with H . parainfluenzae or other bacterial species . The peptide composition of P2 epitopes was determined by analysis of mAb reactivity with a series of overlapping synthetic peptides that covered the amino acid sequences of H . influenzae type b . The domains recognized by these mAbs were completely distinct . mAb P2-18, reactive with an epitope conserved among all H . influenzae P2 porin molecules which were screened, recognized a peptide corresponding to the N-terminal segment (residues 1-14) . The P2-17- and P2-19-specific epitopes were located between residues 28 and 55, and 101 and 129, respectively . None of the epitopes were exposed on the cell surface since no mAbs bound to intact live bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Microbiol Immunol, 1992, 36(3), 205 - 12
The other mediator for adherence of Haemophilus influenzae organisms without involvement of fimbriae; Miyazaki S et al.; The number of the nontypeable Haemophilus influenzae (HiN) organisms that adhered to the primary mouse fetal lung cells was significantly more than type b Haemophilus influenzae (Hib) organisms . The average number of HiN organisms adherent to host cells was 2,291/100 host cells (range, 1,654-3,182), but that of Hib was markedly reduced to 147/100 host cells (range, 102-238) . In this case, P value was less than 0.05 by using a paired Student t-test . The sonicated extract from HiN TMS11 organisms inhibited adherence of H . influenzae TMS11 organisms to monolayer at 76.3% and it inhibited adherence of Hib TMS24 organisms at 92.3% . This result indicates that a mediator existing on the surface of HiN organisms may be the same as that on type b organisms . The number of detected organisms in broncho and lung tissues 3 days after intranasal infection with HiN strains was significantly greater than that in infection with Hib strains . Therefore, in vitro adhesive capacity of H . influenzae organisms was correlative to infectivity by intranasal injection.

Acta Derm Venereol, 1992, 72(1), 37 - 8
Atypical presentation of co-existent Haemophilus ducreyi and Treponema pallidum infection in an HIV-positive male; Abeck D et al.; A 25-year-old homosexual black male presented with asymmetrical perianal ulceration of uncertain clinical origin . Indepth microbiological examination revealed the combined presence of Haemophilus ducreyi and Treponema pallidum . The atypical clinical appearance may have been due to the changed immunological status of the host's being infected with Human Immunodeficiency Virus.

Rev Latinoam Microbiol, 1992 Jan-Mar, 34(1), 61 - 6
{Decrease of spontaneous mutations in Haemophilus influenzae caused by transformation with its own DNA irradiated with near-ultraviolet light}; Alarcon-Hernandez E et al.; Transforming DNA containing the streptomycin resistance marker, was irradiated for 8 h with broad near ultraviolet light (325-400 nm) at pH 4.8, and the inactivation kinetics determined . After selection of streptomycin resistant transformants, they were grown until a turbidity of 150-200 Klett units . In these cultures we looked for new markers coming from the irradiated transforming DNA . We looked and found the novobiocin resistance marker and one that conveys to protoporphyrin IX utilization, measured as an increase in the mutation frequency of these markers in the streptomycin resistant population . In other experiments, we found a decline in spontaneous mutation frequency for the same markers in the cells transformed with irradiated DNA . This last finding rises the possibility of alterations on the mutator genes as a result of near ultraviolet irradiation.

Braz J Med Biol Res, 1992, 25(4), 357 - 67
Comparison of counterimmunoelectrophoresis, latex agglutination and bacterial culture for the diagnosis of bacterial meningitis using urine, serum and cerebrospinal fluid samples; Requejo HI et al.; 1 . Urine, serum and cerebrospinal fluid (CSF) samples from 98 children with clinical and laboratory diagnosis of bacterial meningitis were evaluated by counterimmunoelectrophoresis (CIE) and latex agglutination (LA) methods and the results compared to those obtained with bacterial cultures of the CSF samples . Antigens of Neisseria meningitidis groups A, B and C, Haemophilus influenzae type b and Streptococcus pneumoniae were determined by both immunological methods . Serum was diluted (1:4) with 0.1 M sodium EDTA, pH 7.5, and held at 80 degrees C for 10 min before assay . Polysaccharide of the urine samples was precipitated overnight using an equal volume of 1:1 ethanol-acetone followed by a heat-treatment with 0.1 M sodium EDTA, pH 7.5, at 80 degrees C for 10 min. . 2 . Sensitivity indices were 0.772 (CSF), 0.595 (urine) and 0.317 (serum) for CIE, and 0.914 (CSF), 0.930 (urine) and 0.683 (serum) for LA in relation to the 42 positive bacterial cultures . 3 . The optimal diagnostic efficacy reached 52% for CIE and 72% for LA when urine was concentrated 20- to 30-fold . 4 . These data show that immunological tests of urine samples were more effective than bacterial culture for diagnosing bacterial meningitis and may be indicated when negative results are obtained for CSF tested by bacterial culture and immunoassay methods.

Scand J Infect Dis Suppl, 1992, 83, 26 - 33
Azithromycin in lower respiratory tract infections; Lode H et al.; Azithromycin is a new azalide antimicrobial agent which has a broad spectrum of activity against common lower respiratory tract pathogens including pneumococci, staphylococci, Legionella species, Mycoplasma and Chlamydia species . In particular, it is more active against Haemophilus influenzae than other macrolides . In comparison to other new macrolides, azithromycin achieves higher tissue and intracellular concentrations and these concentrations are sustained for several days after dosing due to a long elimination half-life . The efficacy of azithromycin against lower respiratory tract infections has been proven in several clinical studies . Once-daily dosing with azithromycin, over a 3- or 5- day period was as effective as a 10-day course of other commonly used antibiotics such as amoxycillin/clavulanic acid, erythromycin or cefaclor in lower respiratory tract infections . Azithromycin short-course therapy may offer an advantage in terms of patient compliance and the duration of treatment.

Scand J Infect Dis Suppl, 1992, 83, 22 - 5
Azithromycin in upper respiratory tract infections: a clinical trial in children with otitis media; Pestalozza G et al.; Azithromycin is a newly developed azalide antibiotic which is very active against microbes causing respiratory tract infections; tissue concentrations remain elevated for a long time after discontinuation of treatment . A clinical study was conducted to compare azithromycin (10 mg/kg administered as a single daily dose for 3 days) with amoxycillin/clavulanic acid (50 mg/kg/day given b.i.d . for 10 days) in 30 children with otitis media . Sensitivity testing demonstrated good azithromycin activity against beta-haemolytic streptococci, Moraxella catarrhalis, Haemophilus influenzae and Staphylococcus aureus . By day 12, clinical cure was recorded in 14/15 children treated with azithromycin and this was maintained at day 30 . In the day 12 and 13/15 children by day 30 . It was concluded that a 3-day azithromycin regimen produces a satisfactory clinical response and the eradication of key pathogens, and was acceptable for children.

Pharmacotherapy, 1992, 12(3), 161 - 73
Azithromycin--spectrum of activity, pharmacokinetics, and clinical applications; Drew RH et al.; Azithromycin is an azalide antimicrobial agent . Structurally related to the macrolide antibiotic erythromycin, its mechanism of activity (similar to erythromycin) is interference with bacterial protein synthesis by binding to the 50S component of the 70S ribosomal subunit . Although slightly less potent than erythromycin against gram-positive organisms, azithromycin demonstrates superior activity in vitro against a wide variety of gram-negative bacilli, including Haemophilus influenzae . Absorption is approximately 37% after a 500-mg oral dose . The large volume of distribution (23 L/kg) and low peak serum level (0.4 micrograms/ml) are consistent with data demonstrating extensive tissue distribution and intracellular accumulation . Metabolism is predominantly hepatic (to inactive metabolites), with biliary excretion a major pathway of elimination . Drug elimination is biphasic, with a terminal half-life of up to 5 days . Published trials have examined the efficacy and safety of azithromycin in the treatment of adults with upper and lower respiratory tract infections, skin and skin structure infections, streptococcal pharyngitis, and sexually transmitted diseases . Many used a 5-day course of 250 mg once daily, supplemented with a 250-mg dose on the first day of therapy . Selected trials in sexually transmitted diseases examined single 1-g doses . Promising results also were obtained with oral daily doses of 500 mg in patients with human immunoviral infection who also had Mycobacterium avium complex infection and in animals with toxoplasmosis . Adverse reactions are primarily gastrointestinal (nausea, diarrhea, abdominal pain), with minimal laboratory abnormalities reported . Gastrointestinal tolerance is better than that of erythromycin . Drug interactions have not been observed to date, although coadministration of azithromycin with a large meal may reduce absorption by up to 50%.

J Infect, 1992 Jan, 24(1), 49 - 54
An assessment of sputum induction as an aid to diagnosis of respiratory infections in the immunocompromised child; Foot AB et al.; Sputum induction using nebulised hypertonic saline was performed in two groups of immunocompromised children, one group with symptoms of respiratory infection and one group without . The asymptomatic group were bone marrow transplant (BMT) recipients, all seropositive for cytomegalovirus infection (CMV) . Organisms were identified in three of 14 induced sputum specimens obtained from the symptomatic group (CMV N = 1, Haemophilus influenzae N = 2), but in none of 12 specimens from the asymptomatic group . Adverse effects encountered were minor . Four symptomatic patients with negative induced sputum samples underwent bronchoalveolar lavage, and no further organisms were identified . Sputum induction can be a useful adjunct to the diagnosis of respiratory pathogens in this group of patients.

J Clin Microbiol, 1992 Jan, 30(1), 225 - 6
MIC quality control guidelines for Haemophilus susceptibility tests using cefdinir (FK482), cefepime, cefetamet, cefpirome, ceftibuten, fleroxacin, temafloxacin, clarithromycin, RP59500, and trospectomycin; Bale MJ et al.; A multilaboratory study was performed to establish broth microdilution MIC quality control (QC) guidelines for 10 investigational drugs which previously demonstrated significant activity against Haemophilus influenzae . MIC QC ranges for H . influenzae ATCC 49247 with Haemophilus test medium were determined by using multiple contemporary lots of Haemophilus test medium and the National Committee for Clinical Laboratory Standards' recommended numbers of replicate tests . On the basis of these results, QC ranges (generally modal MIC +/- one log2 dilution) are proposed for cefdinir, cefepime, cefetamet, cefpirome, ceftibuten, fleroxacin, temafloxacin, clarithromycin, RP59500, and trospectomycin . The proposed QC guidelines for clarithromycin and temafloxacin were recently accepted by the National Committee for Clinical Laboratory Standards.

J Singapore Paediatr Soc, 1992, 34(3-4), 141 - 7
Cephalosporins in childhood bacterial meningitis; Donma MM et al.; Bacterial meningitis remains one of the most common life threatening infections of childhood . There exists a conventional therapy for this disease . However, with the increasing incidence of Haemophilus strains resistant to ampicillin and chloramphenicol and Streptococcus pneumonia strains relatively resistant to penicillin, alteration of current therapeutic regimens for meningitis may become necessary . Cephalosporins were considered as alternatives to the conventional therapy for the treatment of bacterial meningitis during the past decade . However, there are still some discrepancies on the use of these against some organisms despite the advent of the cephalosporins . Thus, a review article analyzing quite a number of reliable clinical trials related to cephalosporins for the treatment of bacterial meningitis during the past decade to date is introduced.

Przegl Epidemiol, 1992, 46(3), 245 - 8
{Evaluation of treatment outcome for bacterial meningitis and encephalitis at the provincial hospital of infectious diseases in Wrocław during 1985-1989}; Rotter K; Data about 848 patients treated in the years 1985-1989 in the Province Hospital of Infectious Diseases were analyzed . Among them were 98 patients with bacterial meningitis and encephalitis . The most frequent etiological agents were Neisseria meningitidis and Diplococcus pneumoniae . In none case Haemophilus influenzae was isolated . The average time of hospitalization was limited to 45 days . Treatment introduced at once was based on the results of bacteriological tests . Crystalline penicillin, cephalosporins of the II and the III generation and in some cases metronidazole were antibiotics of choice . Serious complications were observed in 25% of patients . 5% of patients died.

Drugs Exp Clin Res, 1992, 18(8), 319 - 27
Bactericidal activity and postantibiotic effect of cefdinir (Cl 983, FK 482) against selected pathogens; Blandino G et al.; The bactericidal activity and the postantibiotic effect (PAE) of cefdinir (Cl 983, FK 482) (CDR), were determined against Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Branhamella catarrhalis and Escherichia coli (5 strains each) in comparison to erythromycin (E), cotrimoxazole (SXT) and amoxicillin-clavulanic acid (AMC) . Kinetic studies of kill showed that CDR was rapidly bactericidal at concentrations 2 and 4 times the minimum inhibitory concentration (MIC): a reduction of 99.9% in CFU values was observed after 6-8 h for many of the isolates tested . As expected, a PAE was observed when S . aureus was treated with CDR at MIC (range of individual values for 5 strains 0.8-1.5 h) and 4 x MIC (range 1.1-1.4 h) . Moreover, CDR showed a significant PAE at both its MIC and 4 x MIC against S . pneumoniae (range 0.5-1.0 h and 0.9-1.1 h), H . influenzae (range 0.4-0.7 h and 0.4-0.8 h), B . catarrhalis (range 0.5-0.7 h and 0.65-0.95 h) and E . coli (range 0.5-0.6 h and 0.5-0.7 h) . The good bactericidal activity and the significant PAE of CDR against Gram-positive and Gram-negative bacteria (including respiratory pathogens) are a promising indication for the clinical efficacy of this cephalosporin in several bacterial infections.

Chemotherapy, 1992, 38(6), 428 - 32
Inhibition of Haemophilus influenzae adherence to buccal epithelial cells by cefuroxime; Jallat C et al.; We studied the effect of subinhibitory concentrations of cefuroxime on the capacity of Haemophilus influenzae to adhere to buccal epithelial cells (BEC) . Two encapsulated strains (serotype b) and two nonencapsulated, nontypable strains were studied . All four strains adhered strongly to BEC, with indices (mean number of bacteria adhering to a single BEC) ranging from 19 to 48 . Subinhibitory concentrations of cefuroxime (serial dilutions from MIC/2 to MIC/32) were added to cultures in tryptic soy broth and their effect on adherence was tested after 18 h incubation at 37 degrees C . Adherence was diminished by more than 50% by concentrations of cefuroxime ranging from MIC/2 to MIC/8 and varied according to the strain studied . These results show that the adherence of H . influenzae to BEC is inhibited by subinhibitory concentrations of cefuroxime.

Scand J Infect Dis, 1992, 24(6), 759 - 63
Immunoglobulin- and complement-coated bacteria in middle ear effusions during the early course of acute otitis media; Stenfors LE et al.; We used an immunofluorescence assay to investigate the content of secretory IgA- (SIgA), IgG-, IgM- and C3b-coated bacteria in middle ear effusions obtained within 12-72 h after the onset of acute symptoms of purulent otitis in 28 patients (37 ears) . Simultaneously we analyzed the bacteria, both qualitatively and quantitatively, using standard culturing methods and fluorescein conjugated (FITC) antibodies to Haemophilus influenzae and Streptococcus pneumoniae . The ages of the patients were in the range of 5 months to 17 years; 18 were males and 10 females . 73% of the samples harboured no antibody- or C3b-coated bacteria, and particularly those of young patients (< 20 months) . 92% of the samples were culture-positive, while 8% showed dormant bacteria . The predominant species were S . pneumoniae and H . influenzae . In 8% of the samples there was heavy and in 11% slight peripheral SIgA-coating of the 5% showed heavy and 19% slight peripheral IgG-coating . Only 3 samples were intensely opsonized, i.e . the bacteria were coated with IgG and C3b simultaneously . In most cases of acute purulent otitis media, the middle ear cavity of young individuals is not able to coat pathogens with SIgA, IgG, IgM and C3b during the early course of infection.

Postgrad Med J, 1992, 68 Suppl 3, S24 - 8, discussion S29
A multicentre trial of cefaclor advanced formulation versus cefaclor in the treatment of acute bronchitis; Alanis A et al.; Two prospective randomized, double-blind, parallel studies were carried out in Europe to compare cefaclor advanced formulation (cefaclor AF) with cefaclor in the treatment of acute bronchitis caused by susceptible pathogens . A total of 1,321 patients suffering from acute bronchitis confirmed by clinical data and a negative chest X-ray were randomized for treatment in the two multicentre trials . Three doses of cefaclor AF were tested: 375 mg twice daily and 500 mg twice daily were compared with cefaclor 250 mg three times daily; and cefaclor AF 750 mg twice daily was compared with cefaclor 500 mg three times daily . Duration of therapy was seven days . Assessments (complete history, physical examination, sputum specimens for culture and Gram's stain, plus clinical and laboratory evaluations of safety) were carried out within 24 hours before the first dose, during therapy, within 72 hours after therapy completion and, in the 375 mg and 500 mg dose groups, 1-2 weeks after the end of therapy . There were no significant differences between the total evaluable cefaclor AF population and the total evaluable cefaclor population with regard to favourable post-therapy responses . Most favourable clinical and bacteriological response rates in the 375 and 500 mg doses were 80% or above . In the higher dose group, there was a favourable post-therapy symptomatic response in 100% of evaluable patients, with favourable bacteriological responses in 93.3% patients receiving cefaclor AF and 96.8% receiving cefaclor (no significant difference) . Only one serious drug-related adverse event was reported (anaphylactic reaction) . Adverse events related to the digestive system were reported by 4.7% of the cefaclor AF-treated patients and 4.5% of the cefaclor-treated patients during the entire study period . Cefaclor AF, at all three dose levels studies, was seen to be as safe as cefaclor in the treatment of acute bronchitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Moraxella (Branhamella) catarrhalis.

Postgrad Med J, 1992, 68 Suppl 3, S10 - 6
Cefaclor AF: correlation of microbiology and clinical outcome; Thornsberry C; Cefaclor is active against Haemophilus influenzae and Moraxella catarrhalis in addition to the pathogens typically susceptible to first-generation cephalosporins . Cefaclor advanced formulation (cefaclor AF) provides the opportunity for once or twice daily dosing of this agent . Clinical trials using cefaclor AF have been carried out in a number of centres on bacterial infections of the respiratory tract, the urinary tract and the skin . In vitro susceptibility tests on selected pathogens from the clinical trials were carried out according to National Committee for Clinical Laboratory Standards recommendations, generally with excellent agreement between in vitro and in vivo response.

Ann Trop Paediatr, 1992, 12(4), 385 - 9
Indications for lumbar puncture in children presenting with convulsions and fever of acute onset: experience in the Children's Emergency Room of the University of Benin Teaching Hospital, Nigeria; Akpede GO et al.; A total of 522 children, aged 1 month to 6 years, who presented with convulsions and fever of acute onset at the Children's Emergency Room of the University of Benin Teaching Hospital over a 1-year period, were prospectively evaluated . Bacterial meningitis was diagnosed in 22 (4.2%) on bacteriological and/or biochemical evidence . The causative organisms were cultured from the CSF in 13 (Neisseria meningitidis = 7, Streptococcus pneumoniae = 5 and Haemophilus influenzae = 1) and identified by Gram stain only in three (Gram-positive diplococci = 2 and Gram-negative diplococci = 1) . No organisms were identified in the CSF of six of the children with meningitis . The prevalence of meningitis declined sharply after 6 months of age . Six of the children with bacterial meningitis lacked classical meningeal signs but had other indications for lumbar puncture . The following were significantly associated with meningitis: age under 6 months; focal or multiple seizures; absence of a past or family history of seizures; unrousable coma; and an extracranial focus of infection . It is concluded that bacterial meningitis occurs in a good proportion of children, even beyond infancy, with convulsions associated with fever of acute onset, and that decision on the need for lumbar puncture should be guided by clinical features such as age and the presence of complex febrile seizures.

Acta Microbiol Pol, 1992, 41(1-2), 13 - 24
Determination of genome size of Haemophilus influenzae Sb: analysis of DNA restriction fragments; Kauc L; Genomic DNA size was measured in clinical isolates of Haemophilus influenzae by Pulsed-Field Gel Electrophoresis of DNA restriction fragments . Because of the high (64%) A+T content of H . influenzae DNA, restriction enzymes that recognize sequences with at least four GC base pairs were expected to be rare cutters . Five enzymes that produced fragments greater than 200 kb in size were used to digest intact chromosomes and fragments resolved by TAFE and/or FIGE: ApaI (GGGCCC), EagI (CGGCCG), NotI (GCGGCCGC), RsrI (CGGA/TCCG), and SmaI (CCCGGG) . All five had recognition sequences with at least six GC base pairs . The genomic DNA size of H . influenzae serotype b, estimated with ApaI, EagI, NotI, RsrII, and SmaI, is 1,950 kb.

Int Rev Immunol, 1992, 9(1), 45 - 55
The human antibody V region repertoire to the type B capsular polysaccharide of Haemophilus influenzae; Scott MG et al.; The V region repertoire of the human antibody response to the type b capsular polysaccharide of Haemophilus influenzae (Hib-PS) is being defined at the molecular level using antibodies purified from serum of immunized adults . The VH of this response is restricted to the VHIII subgroup while the VL can be divided into two categories . The most common VL, expressed in > 90% of adults and usually constituting the majority of a subjects anti-Hib-PS antibody response, is restricted to the product of a single V kappa II gene known as A2 that probably lacks somatic mutations . The product of the A2 gene is invariably joined to one of several J kappa products by an inserted arginine at the V kappa-J kappa junction . In contrast to the restricted nature of the dominant VL clonotype, the second category of VL constitutes a heterogeneous group of at least seven different VL gene products that often contain somatic mutations and generally exhibit crossreactivity with a related polysaccharide from E . coli . Elucidation of anti-Hib-PS V regions at the molecular level will permit examination of structure-function relationships among these clinically important antibodies and should make the V region repertoire to Hib-PS a useful model for studying human V gene responses.

Am J Med, 1991 Dec 30, 91(6A), 87S - 92S
Treatment of acute exacerbations of chronic bronchitis: state of the art; Chodosh S; Effective treatment of acute bacterial exacerbations of chronic bronchitis (ABE) reduces the number of such exacerbations in such patients and may decrease or eliminate background symptoms and improve pulmonary function . The pathologic and physiologic abnormalities of the bronchial system in chronic bronchitis that predispose to bacterial infection probably include impaired mucociliary clearance, obstructed bronchioles, and bacterial infections of the bronchial epithelium . Exacerbations of bronchopulmonary symptoms are usually observed with ABE, although these symptoms are not unique to ABE . While culture and sensitivity testing is not usually required, microscopic examination of sputum is critical to determine the presence of bacterial infection . Bacteria in numbers significantly above the levels present when the patient's condition is stable and at least a doubling of the sputum neutrophil inflammatory level are essential criteria . Bacterial species observed with ABE include Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Neisseria species, with a lesser incidence of Klebsiella and Pseudomonas species . One or more elements of background therapy for ABE should accompany antimicrobial therapy, for example, physiotherapy, bronchodilators, and so forth . Ampicillin is effective, safe, economical, and thus remains the drug of choice for ABE . Quinolones are an effective alternative when ampicillin cannot be tolerated or if organisms are resistant . Dosing is at the upper range of recommendations, and the chosen drug should be given for a 10-14-day regimen . Patients should be reevaluated if symptoms and physical findings do not return to baseline after 5-7 days.

N Engl J Med, 1991 Dec 26, 325(26), 1837 - 42
Antibody responses to Haemophilus influenzae type B vaccines in men with human immunodeficiency virus infection; Steinhoff MC et al.; BACKGROUND . Persons with human immunodeficiency virus (HIV) infection are at increased risk for serious infections caused by Haemophilus influenzae, yet there are few data on their antibody responses to the H . influenzae type b vaccines . METHODS . We evaluated antibody responses in 248 men who were randomly assigned to receive a single dose of either the H . influenzae type b polysaccharide (PRP) vaccine or the polysaccharide-mutant diphtheria toxoid conjugate vaccine (PRP-CRM) . The subjects were stratified into four groups: seronegative men (67 subjects), men with asymptomatic HIV infection (79), men with symptomatic HIV infection (47), and men with the acquired immunodeficiency syndrome (AIDS) (55) . RESULTS . Before immunization, the subjects with AIDS had the lowest PRP-antibody titers; 40 percent had titers below the putative protective level (less than 0.15 micrograms per milliliter) . In the seronegative subjects, those with asymptomatic HIV infection, and those with symptomatic HIV infection, the PRP-CRM vaccine led to a threefold greater increase in geometric mean antibody titers than did the PRP vaccine (P less than 0.01) . However, the subjects with AIDS had a greater antibody response to the PRP vaccine . The antibody response of HIV-seropositive men to the PRP-CRM vaccine correlated significantly with the number of CD4 lymphocytes (r = 0.47, P less than 0.0001, as compared with r = -0.01 for the PRP vaccine) . In these HIV-infected men, both vaccines elicited the dominant anti-PRP idiotype described previously in populations not infected with HIV . CONCLUSIONS . Immunization with the PRP-CRM conjugate vaccine early in the course of HIV infection is likely to confer protection against disease caused by H . influenzae type b.

J Immunol, 1991 Dec 15, 147(12), 4192 - 9
In vitro induction of a Haemophilus influenzae type b polysaccharide-specific antibody response in human peripheral blood lymphocytes of individuals recently vaccinated with an oligosaccharide-protein conjugate; Peeters CC et al.; In this paper an in vitro culture system for the induction of an antibody response to the Haemophilus influenzae type b polysaccharide (PRP) is described . Anti-PRP IgM and IgG antibody-secreting cells (ASC) and anti-diphtheria toxoid (DT) IgG ASC were detected in cultures of blood B and T cells derived from donors 4 to 6 wk after immunization with Haemophilus influenzae type b oligosaccharide-mutant diphtheria toxin (CRM197) conjugate (HbOC) and required in vitro restimulation with HbOC . When lymphocytes from HbOC-vaccinated donors were stimulated with PRP, anti-PRP IgM and IgG ASC could be detected in 50% offGe cases . Lymphocytes from PRP-vaccinated donors or non-vaccinated donors consistently failed to generate anti-PRP antibodies after in vitro stimulation with HbOC . Optimal in vitro responses were observed at concentrations of 0.06 to 0.6 micrograms/ml of Ag . At higher doses of Ag (6 micrograms/ml) anti-PRP and anti-DT antibody responses were suppressed . The in vitro generation of anti-PRP and anti-DT ASC, as detected by a spot-forming cell assay was shown to be T cell dependent, Ag dependent, and Ag specific . This culture system provides a model for the study of human B cell activation and immunoregulation by polysaccharide-protein conjugates and polysaccharides.

J Infect Dis, 1991 Dec, 164(6), 1149 - 53
Molecular epidemiology of Haemophilus influenzae within families in Santiago, Chile; Lagos R et al.; Thirty-six consecutive patients with invasive Haemophilus influenzae type b (Hib) infections at Roberto del Rio Children's Hospital, Santiago, Chile, were enrolled in a prospective study . Throat cultures were obtained from household contacts of each index case, adjacent neighbors, and matched community control households . Colonization rates for H . influenzae were comparable among groups; however, among household contacts 18% of colonizing isolates were Hib, compared with 2% and 3% among neighbor and community controls . When selected isolates were evaluated further by outer membrane protein (OMP) profiles and multilocus enzyme electrophoresis, only one of the four Hib isolates from household members matched the corresponding index case isolate . One serologically nontypeable isolate from a household contact had an OMP profile and electrophoretic type identical to that of the corresponding Hib index case isolate; hybridization studies with a 9-kb capsular gene probe showed a profile consistent with a capsule-deficient mutant . Hib strains were isolated more frequently from household contacts than from control persons living in Santiago, but colonizing Hib strains were often unrelated to the index case strain.

J Clin Invest, 1991 Dec, 88(6), 2003 - 11
Enhanced attenuation of meningeal inflammation and brain edema by concomitant administration of anti-CD18 monoclonal antibodies and dexamethasone in experimental Haemophilus meningitis; Saez-Llorens X et al.; Antiinflammatory therapy has been shown to reduce the adverse pathophysiological consequences that occur in bacterial meningitis and to improve outcome from disease . In the present study, modulation of two principal steps of the meningeal inflammatory cascade was accomplished by concomitant administration of dexamethasone to diminish overproduction of cytokines in response to a bacterial stimulus and of a monoclonal antibody directed against adhesion-promoting receptors on leukocytes to inhibit recruitment of white blood cells into the subarachnoid space . Dexamethasone and antibody therapy produced a marked attenuation of all indices of meningeal inflammation and reduction of brain water accumulation after H . influenzae-induced meningitis in rabbits compared with results of each agent given alone and of untreated animals . In addition, the enhanced host's meningeal inflammatory reaction that follows antibiotic-induced bacterial lysis was profoundly ameliorated when dual therapy was administered without affecting clearance rates of bacteria from cerebrospinal fluid and vascular compartments . The combination of both therapeutic approaches may offer a promising mode of treatment to improve further the outcome from bacterial meningitis.

Am J Dis Child, 1991 Dec, 145(12), 1374 - 8
The role of corticosteroid therapy in children with pneumococcal meningitis; Kennedy WA et al.; The records of 97 infants and children with pneumococcal meningitis treated in Dallas, Tex, from 1984 to 1990 were reviewed to determine whether corticosteroid therapy improved disease outcome as has been demonstrated in patients with Haemophilus meningitis . Forty-one patients received corticosteroid therapy, 39 of whom were given dexamethasone in the conventional 4-day regimen . There were no significant differences in the demographic and clinical characteristics of steroid- and non-steroid-treated patients . In addition, there were no significant differences between treatment groups with regard to presence of seizures, subdural effusions, hydrocephalus, and positive cerebrospinal fluid cultures 24 hours after the start of treatment . When steroid therapy was given before or concurrently with antibiotic therapy, none of 30 steroid-treated vs 16 of 52 non-steroid-treated patients developed evidence of neurologic or cardiovascular instability after the first parenteral antibiotic dose was given . Among 86 survivors examined, significantly fewer steroid-treated patients had an adverse neurologic long-term outcome, including hearing impairment, compared with non-steroid-treated patients (four of 35 vs 14 of 43) . This was also true for those patients with overwhelming meningeal infection . We believe that corticosteroid therapy is also beneficial in infants and children with pneumococcal meningitis.

J Infect Dis, 1991 Dec, 164(6), 1154 - 9
Serum anticapsular antibody response in the first week after immunization of adults and infants with the Haemophilus influenzae type b-Neisseria meningitidis outer membrane protein complex conjugate vaccine; Daum RS et al.; Eight healthy adults and 48 infants 2 and 4 months old were immunized with Haemophilus influenzae type b-Neisseria meningitidis outer membrane protein complex conjugate vaccine (PRP-OMP) to evaluate antibody kinetics in the first days after immunization . Five adults (63%) had some decrease in antibody, although the geometric mean did not decrease significantly . With one exception, the nadir occurred on postimmunization day 3 . Seven had an antibody increase by day 7 . Of the children, 6 (75%) of 8 and 17 (77%) of 23 had a decrease in antibody in serum obtained on day 2-3 after the first or second dose, respectively, the magnitude of which directly correlated with the preimmunization antibody concentration . However, the geometric mean did not decrease significantly . Within 1 week of immunization, 85% of infants had an increase in antibody, significantly greater after the second dose than after the first . A high concentration of maternally derived antibody before immunization correlated negatively with antibody response . Thus, a transient decrease in antibody occurs in most adults and infants 2-3 days after immunization with PRP-OMP followed by a prompt increase by day 7.

J Immunol, 1991 Dec 1, 147(11), 4007 - 13
Clonal characterization of the human IgG antibody repertoire to Haemophilus influenzae type b polysaccharide . IV . The less frequently expressed VL are heterogeneous; Scott MG et al.; We previously demonstrated that the human anti-Haemophilus influenzae type b polysaccharide (Hib-PS) VL repertoire is dominated by a product of the V kappa II gene, A2, and that V kappa II-A2 anti-Hib-PS antibodies have little or no somatic mutation in VL . To further study this VL repertoire, we studied non-A2 anti-Hib-PS antibodies that were identified either serologically or by amino-terminal amino acid sequence analysis . Of 15 non-A2 anti-Hib-PS antibodies from 12 vaccinated adults, we found four V lambda, five V kappa I, one non-A2 V kappa II, four V kappa III, and one V kappa IV antibodies . As expected, all but two of these subjects also produced V kappa II-A2 antibodies . Interestingly, one of these subjects lacks the A2 gene in the germ line . However, both subjects who did not produce detectable V kappa II antibody did produce normal amounts of total anti-Hib-PS antibody after vaccination . Candidate V kappa genes for the non-A2 antibodies were identified by comparison of up to 60 VL amino acid residues, including CDR1 and CDR2, with all sequenced V kappa genes . V kappa I antibodies appear to be products of three newly sequenced V kappa I genes, O8, O18, and L11, that are reported here . The O8 and O18 genes encode identical amino acid sequences . The non-A2 V kappa II antibody is a likely product of the A1 or A17 genes, the V kappa III antibodies are likely products of the A27 gene, and the V kappa IV antibody is a product of the single V kappa IV gene, B3 . Unlike V kappa II-A2 antibodies, the V kappa I, V kappa III, and V kappa IV antibodies differed by one to five CDR residues from the germ line product of the candidate genes, suggesting the presence of somatic mutations . Thus, anti-Hib-PS antibodies can be divided into two types, the most frequently observed A2 antibodies with little or no somatic mutation and non-A2 antibodies that likely contain somatic mutations.

J Bacteriol, 1991 Dec, 173(23), 7449 - 57
Copper-zinc superoxide dismutase of Haemophilus influenzae and H . parainfluenzae; Kroll JS et al.; Copper-zinc superoxide dismutase ({Cu,Zn}-SOD) is widely found in eukaryotes but has only rarely been identified in bacteria . Here we describe sodC, encoding {Cu,Zn}-SOD in Haemophilus influenzae and H . parainfluenzae, frequent colonists and pathogens of the human respiratory tract . In capsulate H . influenzae, sodC was found in only one division of the bacterial population, and although the protein it encoded was clearly {Cu,Zn}-SOD from its deduced sequence, it lacked enzymatic activity . In H . parainfluenzae, in contrast, active enzyme was synthesized which appeared to be secreted beyond the cytoplasm when the gene was expressed in Escherichia coli minicells . The origin of gene transcription differed between the Haemophilus species, but protein synthesis from cloned genes in vitro was comparable . A C-T transition was found in the H . influenzae sequence compared with the H . parainfluenzae sequence, leading to a histidine, known to be crucial in eukaryotic {Cu,Zn}-SOD for copper ion coordination and so for enzymatic activity, to be changed to tyrosine . This is speculated to be the cause of inactivity of the H . influenzae enzyme . Secreted SODs have only been described in a few bacterial species, and this is the first identification of {Cu,Zn}-SOD in a common human upper respiratory tract colonist . The role of secreted bacterial SODs is unknown, and we speculate that in Haemophilus species the enzyme may confer survival advantage by accelerating dismutation of superoxide of environmental origin to hydrogen peroxide, disruptive to the normal mucociliary clearance process in the host.

Infect Immun, 1991 Dec, 59(12), 4576 - 82
Antibody to a 145-kilodalton outer membrane protein has bactericidal activity and protective activity against experimental bacteremia caused by a Brazilian purpuric fever isolate of Haemophilus influenzae biogroup aegyptius . The Brazilian Purpuric Fever Study Group; Rubin LG et al.; The immunologic basis for protection against Brazilian purpuric fever, a septicemic infection associated with Haemophilus influenzae biogroup aegyptius bacteremia, is unknown . Passive immunization of infant rats with antiserum to whole bacterial cells of the homologous strain protects them from experimental bacteremia following bacterial challenge . In immunoblotting, antibody to a 145-kDa protein (P145) was present in protective antisera but not in nonprotective antisera . As judged by analysis of the antibodies eluted from whole bacterial cells and the agglutination of bacteria by antisera to P145, this protein is surface exposed . We prepared monospecific rat antisera to this protein by three methods: (i) immunization with whole bacterial cells and absorption with a Brazilian purpuric fever strain not expressing P145, (ii) immunization with gel-purified P145, and (iii) immunization with a P145-expressing transformant of a laboratory H . influenzae strain expressing this protein and absorption of the antiserum with the laboratory H . influenzae strain . These antisera had low antilipooligosaccharide antibody titers, were reactive only with P145, and had bactericidal activity in vitro . Following passive immunization, these antisera partially protected infant rats from bacteremia resulting from intraperitoneal challenge with bacteria . As assessed by immunoblotting, pooled adult human sera contained antibodies reactive with P145 . Antibody to P145 may contribute to protection against Brazilian purpuric fever.

Infect Immun, 1991 Dec, 59(12), 4295 - 301
Characterization of immunodominant surface antigens of Haemophilus somnus; Corbeil LB et al.; An immunodominant Haemophilus somnus outer membrane protein with an apparent molecular mass of 40 kDa on Western blots (immunoblots) of gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels was characterized because a monospecific antibody against this antigen was protective . This monospecific antibody was used for immunoaffinity purification of the antigen . The immunoaffinity-purified antigen reacted with a polyclonal antibody to the 40-kDa antigen but not with a monoclonal antibody (3G9) which reacted with the 40-kDa antigen in gradient gels . On 8 or 10% gels, the approximately 40-kDa antigen was resolved as two bands, a 40-kDa band which reacted with the protective monospecific polyclonal antibody (p40) and a band of lower molecular mass which reacted with monoclonal antibody 3G9 . The latter antigen was designated p39 . Both antigens were conserved in all H . somnus isolates tested . The specific antibodies were also used to detect cross-reacting antigens in other gram-negative bacteria . Antibody to p40 reacted with proteins of 55 to 28 kDa, with the greatest intensity shown among proteins from other members of the family Pasteurellaceae . Antibody to p40 was reduced by absorption with live H . somnus or other members of the family Pasteurellaceae, so the antigen appears to be surface exposed . Antibody to p39 only cross-reacted with a broad band (38 to 40 kDa) in Haemophilus agni . Since H . agni is not a bovine pathogen and since convalescent-phase serum from H . somnus-infected animals did recognize p39, the latter may be a good immunodiagnostic antigen, if the lack of cross-reactivity with antigens in other gram-negative bacteria is confirmed with a polyclonal antibody to p39 . The cross-reactivity of antiserum to p40 with antigens of members of the family Pasteurellaceae and the ability of this antiserum to protect against H . somnus pneumonia indicate that p40 may be a useful vaccine antigen for H . somnus disease and perhaps even diseases caused by other members of the family Pasteurellaceae.

Arch Dermatol, 1991 Dec, 127(12), 1823 - 7
Cultural diagnosis of chancroid; Jones CC et al.; Culture of Haemophilus ducreyi remains the definitive way to diagnose chancroid . Since its discovery in 1889, cultural isolation of this fastidious organism has been a challenge for clinicians and microbiologists . A recent chancroid epidemic in our locale prompted a review of available culture techniques . Despite the development of various selective solid media in the last 20 years, cultural diagnosis of chancroid remains problematic . Many pitfalls may complicate this procedure, such as concomitant syphilis, syphilis, or herpes progenitalis simulating chancroid, strain differences in nutritional requirements, improper handling and delayed inoculation of clinical specimens, use of suboptimal growth conditions, and vancomycin hydrochloride-sensitive organisms . Highest cultural yield will be obtained by using enriched gonococcal agar base and enriched Mueller-Hinton agar in a biplate fashion . As most isolates are sensitive to vancomycin, incorporation of this antibiotic should be routine . However, screening for vancomycin-sensitive organisms is indicated when negative cultures are repeatedly obtained from clinically typical cases originating from the same community . Development of immunodiagnostic and DNA probe tests is underway.

J Clin Pharmacol, 1991 Dec, 31(12), 1146 - 50
Bactericidal activity of clarithromycin and its 14-hydroxy metabolite against Haemophilus influenzae and streptococcal pathogens; Gu JW et al.; The serum bactericidal activity of clarithromycin in six normal human volunteers was determined after oral doses of 500 mg . The mean plasma levels of clarithromycin plus 14-hydroxy clarithromycin were 2.11 micrograms/mL after the second dose and 4.36 micrograms/mL after the sixth dose . The mean serum bactericidal titer against Haemophilus influenzae after the second dose was 1:8 and after the sixth dose 1:16 when unheated serum was used . Similar values were obtained when serum to which clarithromycin and 14-hydroxy clarithromycin was added was tested . Mean serum bactericidal titers against H . influenzae determined in Haemophilus test broth or heated serum were 1:2 and 1:4, respectively . Against Streptococcus pneumoniae and Streptococcus pyogenes, there was greater than 1:16 serum bactericidal levels at 12 hours after the sixth dose of clarithromycin.

Enferm Infecc Microbiol Clin, 1991 Dec, 9(10), 624 - 6
{Haemophilus influenzae and genital infection}; Bosch J et al.; We report nine cases of H . influenzae genital infections in women . Six patients had a total of 7 episodes of Bartholin glands abscess . One patient developed a post-caesarean endomyometritis on the 16th post-delivery day . The remaining patient developed an amniotic fluid infection in the 32nd week of pregnancy . All the nine H . influenzae strains were sensitive to ampicillin . We assess the rising importance of H . influenzae as an etiologic agent of female genital tract infections.

Semin Respir Infect, 1991 Dec, 6(4), 247 - 53
Nontuberculous respiratory infections among the homeless; O'Connell JJ; In contrast to the extensive studies of pulmonary tuberculosis among homeless persons, virtually no data are available on nontuberculous respiratory infections in this population . This article reviews the literature on pulmonary infections and homelessness . The clinical experience of the Boston Health Care for the Homeless Program is detailed, with emphasis on the role of multidisciplinary teams of physicians, nurses, and case workers in the integration of hospital- and shelter-based clinics necessary to provide primary care to a fragmented and transient population . The shelters facilitate the transmission of airborne pathogens, and homeless persons are often debilitated and susceptible hosts . Outbreaks of specific respiratory infections are examined, including pneumococcal pneumonia, Haemophilus influenzae type b pneumonia, and influenza.

Semin Respir Infect, 1991 Dec, 6(4), 217 - 24
Acute respiratory infections in children in the developing world; Douglas RM; The profound decline in death rates from respiratory infections in recent decades in the developed countries of the world is a complex phenomenon that probably results from a combination of socioeconomic and environmental change and modern medical care . Death rates from respiratory infections in the developing world are very variable, and there is evidence that they can decrease dramatically when effective health services are engrafted onto a social environment in which mothers are literate and trained to observe their children's health . A worldwide case management program aimed at making lifesaving antibiotics and oxygen available for treatment of children in deprived areas is currently being spearheaded by the World Health Organization and rests on simplified approaches to diagnosis that are widely disseminated to parents and primary health workers . These guidelines have been shown in field studies to contribute to changes in child mortality . The epidemiology of pneumonia in childhood seems similar worldwide . Most children suffer five to eight respiratory infections annually if they live in the cities and fewer if they live in rural areas but, in deprived circumstances, pneumonia complicates the infection much more often and the principal organisms are pneumococcus and Haemophilus influenzae . A vaccine approach to these two organisms is attractive and needs further field testing . Meanwhile, a case management approach, making antibiotics available on a rational basis worldwide, is capable of saving lives . Until mothers in the developing world have confidence in the survival of their children, they are unlikely to be attracted to control of their fertility.

Aust Vet J, 1991 Dec, 68(12), 387 - 90
Meningoencephalitis and other conditions associated with Histophilus ovis infection in sheep; Philbey AW et al.; Histophilus ovis was isolated from 29 sheep in 20 flocks and 2 artificial insemination (AI) centres in southern New South Wales from 1984 to 1990 . The clinical and pathological findings were consistent with previous reports and included polyarthritis (7 flocks), epididymo-orchitis (5), meningoencephalitis (3), pneumonia (3), septicaemia (2), mastitis (1) and metritis (1) . Six sheep had meningoencephalitis, a syndrome not previously associated with H ovis infection in sheep, which was similar pathologically to thromboembolic meningoencephalitis in cattle, caused by the related organism, Haemophilus somnus . H ovis was isolated from the semen of 12-month-old rams in a flock that had polyarthritis due to H ovis, in 4-month-old ram lambs and from the uterus of a ewe in a flock that had sporadic cases of H ovis septicaemia.

Minerva Pediatr, 1991 Dec, 43(12), 753 - 75
{Rational bases of current etiopathogenetic therapy of bacterial meningitis . Review of the literature and personal experience in 122 pediatric cases}; Pecco P et al.; Bacterial meningitis is a serious infectious disease, the course of which depends on the correct use of antibiotics and an intensive symptomatic and support therapy . The presence of microbes and their fractions in the CNS determines inflammatory phenomena that lead, through complex mechanisms, to the supportive treatment has the purpose of curbing the inflammatory phenomena, reducing cerebral oedema and avoiding ischaemia . This therapy makes use of cortisone and mannitol . The effectiveness of cortisone in reducing cerebral damage and, consequently, the neurological sequelae of the disease has been documented in experimental models and in man . After analysing the pathogenetic events of cerebral damage and the rationale of the treatment, reference is made to a personal therapeutic protocol that includes an aetiological treatment (Ceftriaxone 100 mg/kg/die), a support therapy (dexamethasone 0.2-0.3 mg/kg/die, mannitol, water restriction) and a symptomatic therapy (for convulsions, high temperature and shock) . Both the antibiotic and cortisone are also introduced into the spine on the occasion of lumbar injection . 122 children suffering from non-tubercular bacterial meningitis, admitted to the Emergency Department of the Regina Margherita Infant Hospital of Turin in the period 1984-89, were treated . A further 7 patients, admitted for the same pathology, died within a few hours . In 88% of cases, aetiological agents were found by bacterioscopic and/or cultural and/or co-agglutinin on liquor examination (Neisseria meningitidis 47.5%, Haemophilus influenzae 20.5%, Streptococcus pneumoniae 15.6%, others 4.1%) . The patients were treated with support therapy for as long as clinical conditions required it and with Ceftriaxone until clinical cure, end of fever and normalisation of PRC . In the reported series, 90% of patients were treated for from 3 to 6 days . This duration of antibiotic therapy is shorter than that reported and recommended in the literature . Therapeutic results were very good with 95% cure without neurological sequelae even at 6 month/1 year follow-up . Only 6 patients reported sequelae (2 irritative anomalies at EEG, 3 hypoacusis, 12 psychomotor retardation) . The results were also better than those reported in the Italian and foreign literature . The Authors are convinced that, in the hands of experienced physicians, timely antibiotic, anti-inflammatory, cerebral anti-oedema and symptomatic treatment will improve the prognosis for bacterial meningitis in infancy.

Pediatr Emerg Care, 1991 Dec, 7(6), 337 - 42
An approach to the diagnosis and treatment of membranous laryngotracheobronchitis in infants and children; Gallagher PG et al.; The purpose of this study is to report 18 cases of membranous laryngotracheobronchitis (MLTB) and to review 143 published cases in order to accurately characterize the epidemiology, presentation, clinical course, treatment, and outcome of patients with this disorder . The male:female ratio was 2:1; mean age was four years . Most patients presented with acute onset of respiratory distress with fever, toxicity, and stridor after a prodrome of upper respiratory tract infection lasting a few days . White blood cell counts varied over a wide range, and blood culture results were rarely positive . Respiratory cultures commonly yielded Staphylococcus aureus or Haemophilus influenzae . Diagnosis was usually confirmed by airway radiographs or endoscopy . An artificial airway was required in 83% of patients . Complications included respiratory failure, toxic shock syndrome, anoxic encephalopathy, and death . MLTB is a serious, potentially fatal cause of acute infectious airway obstruction in infants and children that requires an organized approach to diagnosis and management.

Pediatr Emerg Care, 1991 Dec, 7(6), 331 - 3
Haemophilus influenzae type b bacteremia in older children; King BR et al.; Haemophilus influenzae type b (HIB) is a well-recognized cause of serious infection in infants and toddlers . However, little information exists regarding HIB infections in older children . This report describes serious HIB infections in 23 children (eight immunocompromised; 15 immunocompetent) older than 59 months of age . Data were collected over an 11-year period . The mean age of the children was 7.6 years (range, 5-15 years), and 14 were male . While three of the eight immunocompromised children had HIB pneumonia, none of the immunocompetent group had this diagnosis . Eleven of the 15 immunocompetent children had epiglottitis or meningitis . HIB bacteremia without focal infection occurred in four children, two immunocompromised and two immunocompetent . This study supports the recommendation of empiric HIB antibiotic therapy for children up to 12 years of age who have serious infections . Antibiotics effective against HIB should be included in the presumptive antibiotic therapy of seriously ill immunocompromised children, regardless of age.

Kinderarztl Prax, 1991 Dec, 59(12), 365 - 7
{Type B Haemophilus influenzae infections: epidemiology, vaccination, chemoprophylaxis}; Noack R et al.; In the new countries of the Federal Republic Germany the incidence of systemic Hib-infections is lower than in the old FRG . In children under the age of 5 years the incidence of Hib-meningitis is 8/100,000 and of all systemic Hib-diseases about 17/100,000 . By Hib-vaccination (PRP-D) severe diseases can be prevented . The recommended chemoprophylaxis with Rifampicin is important in this connection, too.

Pneumologie, 1991 Dec, 45(12), 987 - 90
{Ciliary function in bronchopulmonary infections in childhood}; Rhodius U et al.; It was the aim of this study to examine the influence of bacterial or viral infections of the airways on the ciliary beat rate in childhood . In 21 children with bacterial bronchopulmonary infections a mean ciliary beat rate of 9.1 +/- 2.4 . Hz was found that did not differ significantly from that of the group of the healthy subjects (9.9 +/- 1 Hz) . In 7 of the 21 patients we could identify an infection of the respiratory tract with Haemophilus influenzae; in those children there was a marked reduction of the mean ciliary beat rate at 8 Hz . 13 children with viral bronchopulmonary infections had a mean ciliary beat rate of 11.8 +/- 1.8 Hz, which is significantly enhanced when compared with that of the healthy group . Compared with the mean ciliary beat rate of bacterial infections of the respiratory tract there is a significant difference . In viral infections of the airways no value below 9 Hz was found . In case of markedly reduced ciliary beat rate a bacterial infection must be assumed.

Clin Pediatr (Phila), 1991 Dec, 30(12), 673 - 5
Bacterial meningitis--an update; Marks MI; This report emphasizes new clinical information about bacterial meningitis in infants and children . Important elements of diagnosis include examination for the presence of shock and increased intracranial pressure . In such cases, initial treatment should focus on appropriate fluid therapy, administration of oxygen, reduction of intracranial pressure and use of corticosteroids . Currently, antibiotics of choice include ampicillin plus either cefotaxime or ceftriaxone in young infants, and one of these cephalosporins in older patients (beyond 3 months of age) . Shorter durations of therapy (5 to 7 days for meningococcus, 7 days for haemophilus and 7-10 days for pneumococcus) are now commonly employed . In many centers, dexamethasone is started before the first dose of antibiotic and continued for 4 days to reduce neurologic and audiologic sequelae . Future trends will include studies of endotoxin neutralizers and non-steroidal anti-inflammatory drugs to reduce further tissue injury in meningitis . Prevention of meningitis is the ultimate goal . Since Haemophilus influenzae vaccination can now begin at 2 months, this approach may bring important results soon.

J Clin Invest, 1991 Dec, 88(6), 1811 - 8
An idiotypic marker associated with a germ-line encoded kappa light chain variable region that predominates the vaccine-induced human antibody response to the Haemophilus influenzae b polysaccharide; Lucas AH et al.; Human antibodies specific for the Haemophilus influenzae b polysaccharide (Hib PS) frequently express a cross-reactive idiotype (CRI), and commonly utilize a VL region that is the product of the V kappa II gene A2 . To examine further anti-Hib PS V region expression and to determine whether CRI expression is correlated with the V kappa IIA2 chain, we isolated a monoclonal antibody (MAb) reactive with an idiotypic determinant of anti-Hib PS antibodies . This MAb inhibited Hib PS binding but did not react with Ig isotypic determinants . The CRI recognized by this MAb, designated HibId-1, was associated with the Hib PS-combining site since the reactivity of the MAb with anti-Hib PS antibodies could be inhibited by Hib PS . HibId-1 was expressed by 17 of 17 clonally purified and sequence-defined anti-Hib PS antibodies having V kappa IIA2 L chains . In contrast, 0 of 10 anti-Hib PS antibodies having either V lambda, V kappa I, or V kappa III chains expressed HibId-1 . Western blot analysis showed that the MAb anti-CRI reacted with isolated anti-Hib PS V kappa IIA2 L chains but not with H chains or other L chains, indicating that the HibId-1 determinant is localized to the V kappa IIA2 chain, and does not require pairing with H chain for expression . Anti-Hib PS antibodies bearing HibId-1 were present in at least 85% of subjects immunized with either free Hib PS or Hib PS coupled to diphtheria toxoid (Hib PS-DT), and comprised on the average 60% of the total vaccine-induced serum anti-Hib PS . HibId-1 expression was not related to age at vaccination inasmuch as infants, children, and adults had similar distributions of HibId-1-positive anti-Hib PS after vaccination with Hib PS-DT . HibId-1 was expressed at a lower frequency and comprised a smaller fraction of the total anti-Hib PS antibody in adult preimmunization sera as compared to post-Hib PS immunization sera, suggesting that immunization preferentially stimulates HibId-1-positive B cells . These data demonstrate that antibodies bearing HibId-1/V kappa IIA2 comprise a predominant component of the anti-Hib PS response induced by immunization, and that this pattern of VL expression is established early in ontogeny.

J Med Microbiol, 1991 Dec, 35(6), 363 - 6
Histidine decarboxylases from bacteria that colonise the human respiratory tract; Cundell DR et al.; We investigated whether production of histamine by bacteria isolated from sputum of patients with infective lung diseases could be attributed to the presence of histidine decarboxylase (HD) . Twenty gram-positive and 20 gram-negative organisms were studied for their ability to decarboxylate 14C-histidine in vitro over the pH range 4.5-7.5 . Of the bacteria investigated, lysates from the gram-negative species Haemophilus influenzae, H . parainfluenzae, Moraxella (Branhamella) catarrhalis and Pseudomonas aeruginosa liberated 14CO2 and histamine from 14C-histidine in the presence of the cofactor pyridoxal phosphate . In contrast, results obtained in the absence of cofactor were similar to those of negative (lysate-free) controls suggesting that the HD enzymes of these species resembled those previously described in other gram-negative bacteria . No HD activity was detected over this pH range in lysates from gram-positive species . This finding correlated with earlier observations that these gram-positive organisms did not produce histamine in vitro.

Infect Immun, 1991 Dec, 59(12), 4371 - 6
Distinct pattern of antibody reactivity with oligomeric or polymeric forms of the capsular polysaccharide of Haemophilus influenzae type b; Pillai S et al.; The chain length of oligosaccharides required for antibody binding has been studied by using the capsular polysaccharide from Haemophilus influenzae type b or oligosaccharides derived from it . The concentration of competing antigens required to achieve a 50% inhibition of antibody binding by human polyclonal antisera in an in vitro competition enzyme-linked immunosorbent assay decreased progressively from greater than 10(-3) to 5 x 10(-7) M as the inhibiting saccharide chain length increased from 1 to 262 repeat units . Even small oligosaccharides (one or two repeat units) are potentially capable of competing to a significant level if a high enough concentration of saccharides is used . A similar pattern of reactivity was seen with a monoclonal anti-polyribosyl ribitol phosphate antibody, suggesting that the differences in the avidity of the antibody subpopulations in the polyclonal antisera do not contribute to the binding patterns observed . The binding reaction was specific as evaluated with pneumococcal saccharides . Furthermore, an oligosaccharide-protein conjugate binds antibody better than the free oligosaccharides do . Such a difference in binding was not observed between the polysaccharide and a polysaccharide-protein conjugate . Overall, the data suggest that identical epitopes are expressed by oligomeric and polymeric forms of the antigen and that a particularly more stable conformation in polysaccharides is preferred by antibodies . Covalent coupling of oligomers to protein increases the expression of stable conformation of epitopes . The data further suggest that this kind of antigenic analysis may be important for the design and synthesis of glycoconjugate vaccines.

Infect Immun, 1991 Dec, 59(12), 4724 - 8
Inability to express fimbriae results in impaired ability of Haemophilus influenzae b to colonize the nasopharynx; Weber A et al.; We cloned into the structural fimbrial subunit gene from a fimbriated Haemophilus influenzae b a 1.5-kb kanamycin resistance gene . The resultant strain (RKAW5) was tested by Southern analysis, hemagglutination, and electron-micrographic examination to confirm gene inactivation . In comparison with the parent, RKAW5 exhibited a significant decrease in adherence to human buccal epithelial cells and in nasal colonization of yearling rhesus monkeys.

Infect Immun, 1991 Dec, 59(12), 4473 - 7
Blocking of fimbria-mediated adherence of Haemophilus influenzae by sialyl gangliosides; van Alphen L et al.; The structure of the receptor for the fimbriae of Haemophilus influenzae on human oropharyngeal epithelial cells and erythrocytes was determined in inhibition experiments with various sugars, glycolipids, and glycoproteins . Of 30 monosaccharides and disaccharides at a concentration of 0.1 M and of 3 polysaccharides at a concentration of 1 mg/ml, none inhibited fimbria-specific adherence and hemagglutination . Inhibition was obtained with gangliosides GM1, GM2, GM3, and GD1a in nanomolar concentrations, whereas the asialo derivative of GM1, sialyl-lactose, and sialoglycoproteins were poor inhibitors . These findings indicate that sialyl-lactosylceramide (GM3) is the minimal structure for the fimbria-dependent binding of H . influenzae to its receptor on oropharyngeal epithelial cells and erythrocytes . As is the case with GM2, substitution of GM3 with N-acetylgalactosamine makes the molecule a 10-fold-better receptor analog.

Am J Dis Child, 1991 Dec, 145(12), 1379 - 82
Haemophilus b disease after vaccination with Haemophilus b polysaccharide or conjugate vaccine; Frasch CE et al.; The reported frequency of invasive Haemophilus influenzae type b disease occurring within 1 year after immunization was compared in American children who received either Praxis Biologics' Haemophilus b polysaccharide vaccine or Connaught Laboratories' Haemophilus b conjugate vaccine during the first year of distribution . All domestic cases reported to the Food and Drug Administration or the Centers for Disease Control were included in the study . An estimated 4.5 million and 2.0 million doses of polysaccharide and conjugate vaccines were administered, respectively . Approximately three cases of early-onset disease (disease developing less than 15 days after vaccination) per million doses were reported for the polysaccharide compared with four cases per million doses for the conjugate vaccine . There were 30.7 reported vaccine failures per million doses of the polysaccharide vaccine compared with 9.0 per million doses of the conjugate vaccine, a 3.4-fold difference . The reporting rate ratios (cases of vaccine failure to cases of early-onset disease) for the polysaccharide and conjugate were 11.5 and 2.3, respectively, a fivefold difference . Thus, compared with recipients of the polysaccharide vaccine, vaccine failures reported among recipients of the conjugate vaccine were 80% fewer than expected.

Oral Microbiol Immunol, 1991 Dec, 6(6), 363 - 72
Sensitivity of Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus to oxidative killing; Dongari AI et al.; We examined the killing of Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus by oxygen metabolites generated by the xanthine-xanthine oxidase (X-XO) system . This system generates a mixture of oxidants, including superoxide radical, hydrogen peroxide, hydroxyl radical, and possibly singlet oxygen . Differential sensitivity to the X-XO system was observed among strains of A . actinomycetemcomitans; notably, 2 catalase-deficient strains and 2 strains representative of serotypes b and c were the most susceptible . H . aphrophilus was not sensitive . The amount of oxidants produced by the X-XO system more closely correlated with killing than the ratio of oxidant production . Cytochrome c, superoxide dismutase, catalase, dimethyl sulfoxide, and desferrioxamine were used to determine the role of superoxide radical, hydrogen peroxide and hydroxyl radical in the bactericidal process . Hydrogen peroxide was the major bactericidal agent against A . actinomycetemcomitans . Superoxide anion participated in killing of A . actinomycetemcomitans to varying but lesser degrees . The intracellular generation of hydroxyl radical was implicated in the killing of several strains . We conclude that (i) strains of A . actinomycetemcomitans are differentially sensitive to the bactericidal effects of the X-XO system and (ii) of the oxidants produced by the X-XO system, hydrogen peroxide is the most bactericidal against A . actinomycetemcomitans.

J Antimicrob Chemother, 1991 Dec, 28 Suppl C, 121 - 30
The role of temafloxacin in the community setting: an overview; Ball P; The use of new quinolones has become established therapy for many community infections including urinary tract infection, genital infection, soft tissue infection and some forms of lower respiratory tract infection . However, there has been an undercurrent of anxiety concerning their efficacy in pneumococcal infections . Temafloxacin has improved activity against pneumococci and its high oral bioavailability and excellent penetration into respiratory tissues now combine to provide a suitable profile for the management of a wider range of respiratory infections . Eradication rates in acute exacerbations of chronic bronchitis collated from individual studies are 98% overall and 100% in pneumococcal infections . Furthermore, eradication rates in smokers and the elderly illustrate significant advantages for temafloxacin when compared with previous quinolones . In pneumonia, a twice-daily temafloxacin regimen has given equivalent overall results to those of amoxycillin (84.6% vs 80%) . In proven pneumococcal pneumonia, equivalent results (78.6% vs 78.4%) have been obtained with both drugs . A daily 600 mg dose of temafloxacin eradicated 94% of pneumococcal isolates in one study and in another this agent given twice-daily orally proved comparable to parenteral cephalosporin treatment . Temafloxacin shares with other quinolones excellent bacteriological and clinical efficacy against Haemophilus influenzae and Moraxella catarrhalis . These results and the lack of potential interaction with theophylline indicate temafloxacin to be suitable for domiciliary management of respiratory tract infections in addition to a broad range of other community infectious diseases.

J Vet Pharmacol Ther, 1991 Dec, 14(4), 400 - 10
Clinical pharmacokinetics of parenterally administered danofloxacin in cattle; Giles CJ et al.; Danofloxacin is a new fluoroquinolone antibacterial, developed specifically for veterinary use . Its in vitro activity and pharmacokinetic properties have been investigated to assess its potential for use in the therapy of respiratory disease in cattle . The minimum inhibitory concentration of danofloxacin against 90% (MIC90) of contemporary European and North American field isolates of Pasteurella haemolytica, Pasteurella multocida and Haemophilus somnus, the most important bacterial respiratory pathogens of cattle, was 0.125 micrograms/ml . The plasma and lung kinetics of danofloxacin following parenteral administration of 1.25 mg/kg were evaluated in two studies . Danofloxacin was rapidly absorbed following intramuscular and subcutaneous injection and bioavailability was virtually complete (101% and 94% respectively) . Plasma concentration profiles of danofloxacin were similar for intramuscular and subcutaneous routes with no significant differences in the area under the plasma concentration-time curves (AUC) following one, three or five consecutive daily doses, although slightly higher peak plasma concentrations were achieved by the intramuscular route . Following intramuscular administration, the mean peak lung concentration of danofloxacin was 4.1 times greater than that of plasma . Similarly, the AUC for lung tissue was 3.7 times greater than that for plasma . These data indicate that danofloxacin should be particularly appropriate for the therapy of bacterial respiratory disease in cattle.

Am J Epidemiol, 1991 Nov 15, 134(10), 1212 - 21
Effects of age, breast feeding, and household structure on Haemophilus influenzae type b disease risk and antibody acquisition in Alaskan Eskimos; Petersen GM et al.; Invasive Haemophilus influenzae type b (Hib) disease occurs with unusually high incidence in Alaskan Eskimos . In 1983, the authors evaluated the unique susceptibility of the Yupik-speaking Eskimo population in southwest Alaska . A matched case-control design was used to assess the influence of age, breast feeding, and household composition on disease risk, with a historical cohort design to evaluate their effects on acquisition of Hib anticapsular antibody . The authors studied 103 cases with known invasive Hib disease that occurred at a mean age of 8.7 +/- 8.6 months; healthy controls were matched for age and village of residence . Living in extended families at the time of disease onset was significantly associated with Hib disease (p less than 0.04; odds ratio = 1.8; 95% confidence interval 0.87-3.25) . The authors found that breast feeding was significantly less common among cases than controls (p less than 0.03; odds ratio = 0.53; 95% confidence interval 0.27-0.98) . Although there was a positive correlation between age and acquired level of total anticapsular antibody (r = 0.59; p less than 0.0001), previous exposure to invasive Hib disease did not influence these levels . Household crowding and breast feeding also did not appear to affect Hib antibody acquisition.

Diagn Microbiol Infect Dis, 1991 Nov-Dec, 14(6), 485 - 93
Quality control limits for disk diffusion and broth microdilution susceptibility tests with Haemophilus test medium; Doern GV et al.; A six-center collaborative study was performed with the aim of developing quality control test limits for both disk diffusion and broth microdilution susceptibility tests with Haemophilus influenzae ATCC 49247 using Haemophilus test medium . Quality control ranges are presented for 18 antimicrobials: ampicillin, amoxicillin-clavulanate, ampicillin-sulbactam, cefuroxime, cefamandole, cefonicid, cefotaxime, ceftriaxone, ceftizoxime, ceftazidime, cefixime, chloramphenicol, tetracycline, trimethoprim-sulfamethoxazole, rifampin, imipenem, aztreonam, and ciprofloxacin.

Am Fam Physician, 1991 Nov, 44(5 Suppl), 33S - 40S, 46S-47S
An approach to pediatric upper respiratory infections; Middleton DB; Upper respiratory tract infections are the most common diseases encountered in office pediatrics . The majority of these illnesses, including the common cold and pharyngitis, are viral in etiology, present with rhinitis and fever, and are self-limited and benign . Management consists of fluids, rest, saltwater nose drops and analgesics . Antihistamines appear to relieve only those symptoms potentiated by allergy . With the exception of streptococcal pharyngitis, upper respiratory tract infections do not require antibiotic therapy . However, otitis media and sinusitis, which sometimes are difficult to diagnose, are markedly improved by antibiotics that cover Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis . In 10 percent of children, otitis media and sinusitis are recalcitrant to antibiotic therapy . For these patients, referral to an otolaryngologist, myringotomy, placement of tympanostomy tubes or a short trial of prednisone may be efficacious.

Mutat Res, 1991 Nov, 251(1), 21 - 9
In vitro mutation of Haemophilus influenzae transforming deoxyribonucleic acid by ultraviolet radiation at -70 degrees C; Munoz-Sanchez JL et al.; Previous studies have shown the non-mutability of Haemophilus influenzae either by UV irradiation of the cells or by irradiating the transforming DNA and transformation of competent cells . In the present work, we present evidence of transforming DNA mutation in vitro by UV irradiation at -70 degrees C, which upon transformation of competent cells showed a rise in the mutation frequencies of novobiocin resistance of the order of several hundredfold . Also we performed experiments using the UV-irradiated DNA either sonicated or DNase-treated, which allowed us to propose that such rise in mutation frequency is probably due to the integration of DNA carrying premutagenic photoproducts to the recipient cells' genome . We think that the key point was the low temperature at which the DNA was irradiated in order to obtain the mutagenic effects, since it is likely that at -70 degrees C, the main photoproducts are not the cyclobutane dimers, but are the spore photoproducts, which are probably responsible for the damage that leads to mutagenic effects.

J Infect Dis, 1991 Nov, 164(5), 982 - 6
Reduction of oropharyngeal carriage of Haemophilus influenzae type b (Hib) in children immunized with an Hib conjugate vaccine; Takala AK et al.; The oropharyngeal carriage of Haemophilus influenzae type b (Hib) was studied among 725 healthy 3-year-old children who had or had not been immunized with an Hib conjugate vaccine . Oropharyngeal swabs were collected during the childrens' well-child visit to their local child health center . Fourteen (3.5%) of the 398 unvaccinated children were oropharyngeal carriers of Hib, whereas none of the 327 children who had received Hib conjugate vaccine carried Hib (P less than .001) . Carriage rates of non-type b H . influenzae (19%) or Streptococcus pneumoniae (18%) were the same irrespective of the Hib vaccination status of the children . Thus Hib conjugate vaccine, unlike Hib polysaccharide vaccine, seems to be able to prevent oropharyngeal colonization by Hib.

J Periodontal Res, 1991 Nov, 26(6), 519 - 26
Use of synthetic oligonucleotide DNA probes for the identification of different strains of Fusobacterium nucleatum; Bolstad AI et al.; The ability of three different oligonucleotide probes to identify different oral strains of Fusobacterium nucleatum was tested . Probes 119 and 214 were designed on the basis of known amino acid sequences from the N-terminal end of an outer membrane protein of F . nucleatum strain Fev1 . Probe H 2.1, was a randomly cloned chromosomal DNA fragment of 2.1 kbp . The specificities of the probes were examined by testing each of them against a panel of five other species of Fusobacterium (six strains), oral and non-oral, and also against seven different oral species of six other genera . The chromosomal DNA of the bacteria to be examined was digested to completion using the restriction enzymes HincII, HindIII, EcoRI, EcoRV and Sau3AI . Digests were run on agarose gels and subjected to southern blotting before being hybridized with the probe in question . The results were confirmed by running a slot blot of genomic DNA from all of the 19 strains and hybridizing with a probe H 2.1 . Probe H 2.1 turned out to be the most specific and useful of the three probes investigated . By use of this probe, interstrain identification of the six different strains of F . nucleatum could be performed and the strains could be distinguished from other oral species found in the oral cavity, such as Actinobacillus actinomycetemcomitans, Haemophilus aphrophilus, Capnocytophaga sputigena, Porphyromonas (Bacteroides) gingivalis, Eikenella corrodens and Leptotrichia buccalis . The probe reacted weakly with other non-oral species of the genus Fusobacterium, and there was no problem in distinguishing between the different strains.

Microb Pathog, 1991 Nov, 11(5), 387 - 90
Mouse subcutaneous chamber model for in vivo growth of Haemophilus ducreyi; Trees DL et al.; The ability of Haemophilus ducreyi, the causative agent of chancroid, to grow in subcutaneous chambers implanted in mice was studied . All seven H . ducreyi strains tested were able to maintain a long-term infection in ICR mice; one mouse remained infected with strain Hd175 for more than 4 months . Growth curves obtained following the removal of chamber fluid at various time points from infected mice demonstrated that H . ducreyi was growing during the course of the infection . In addition, all three mouse strains tested (ICR, CBA and BALB/c) were able to maintain long-term H . ducreyi infections . This model will be valuable in studying the effects of in vivo growth on the antigenic composition of H . ducreyi as well as for the identification of virulence factors.

Microb Pathog, 1991 Nov, 11(5), 357 - 65
Phenotype versus genotype of the 19 kD peptido-glycan associated protein of Legionella (PpIA), among Legionellae and other gram-negative bacteria; Ott M et al.; The protein PpIA (19 kD) cloned from a genomic library of Legionella pneumophila, Philadelphia 1, represents a peptido-glycan associated outer membrane protein in recombinant E . coli K-12 and L . pneumophila . It exhibits distinct sequence homology to lipoproteins of Haemophilus influenzae and E . coli . A ppIA specific DNA probe generated by PCR was used in Southern hybridizations of chromosomal DNA of Legionella strains and other Gram-negative pathogens . Under conditions of high stringency, hybridization could only be observed in L . pneumophila isolates, but all other Legionella strains tested displayed hybridization under lower stringency . No signals appeared after hybridization of chromosomal DNA from a variety of other bacteria . Using anti-PpIA monospecific polyclonal antibodies in Western blots, it was demonstrated that PpIA related proteins of nearly the same size are found in all L . pneumophila isolates and in a variety of, but not all, the Legionella species analysed here.

Infection, 1991 Nov-Dec, 19(6), 406 - 8
Cerebrospinal fluid penetration of cefmenoxime in children with bacterial meningitis; Eicken A et al.; Blood and cerebrospinal fluid (CSF) concentrations of cefmenoxime were determined either microbiologically or by means of HPLC in 20 children with proven or suspected bacterial meningitis . Sixteen children suffered from bacterial meningitis: causative organisms were Haemophilus influenzae type b (n = 10), Streptococcus pneumoniae (n = 4) and Neisseria meningitidis (n = 2) . In these patients the cefmenoxime concentration in the CSF ranged from 0.9 to 12.2 mg/l, with a mean concentration of 4.63 mg/l 1.5-3 h after the last intravenous cefmenoxime application and 24-48 h after initiating therapy with 200 mg cefmenoxime/kg/d in four doses . In eight cases the bactericidal titers of the CSF were examined during therapy . Titers between 1:64 and 1:2,048, exceeding the minimal bactericidal concentration, were found . After five doses of cefmenoxime 50 mg/kg, two CSF cultures showed bacterial growth: one H . influenzae (bactericidal titer in CSF 1:256) and one S . pneumoniae.

Indian J Med Res, 1991 Nov, 93, 366 - 70
Clinical & bacteriological profile of neonatal pneumonia; Misra S et al.; In a prospective study of 44 neonates (33 outborn and 11 inborn) with pneumonia, the bacteriology of pneumonia was determined by blood culture and serum counterimmunoelectrophoresis (CIEP) . Twenty-nine babies also underwent lung aspiration . The lung aspirate was subjected to bacterial culture and CIEP . CIEP was done to detect the bacterial antigens of Streptococcus pneumoniae and Haemophilus influenzae . Absence of tachypnoea, found more commonly in low birth weight babies, was a poor prognostic sign . Low birth weight babies had a significantly higher mortality than babies with normal birth weight . Altogether, a bacterial etiology of neonatal pneumonia could be established in 25 cases (56.7%) . In 10 babies, Strep . pneumoniae antigen was detected in serum and/or lung aspirate . Micro-organisms were cultured from blood and/or lung aspirate from 17 babies . Eleven babies (25%) grew Gram negative bacteria . The common bacteria identified in decreasing order of frequency were Strep . pneumoniae, Klebsiella pneumoniae, Staphylococcus epidermidis, Acinatobacter lowfii, Staph . aureus, Pseudoamonas aeruginosa etc . All the Gram negative bacteria as well as staphylococci were sensitive to amikacin while only 23.5 per cent was sensitive to gentamicin . All staphylococci isolated were sensitive to methicillin.

J Reprod Fertil, 1991 Nov, 93(2), 341 - 5
Neutrophil migration into the bovine uterine lumen following intrauterine inoculation with killed Haemophilus somnus; Butt BM et al.; Polymorphonuclear neutrophils (PMN) in bovine uterine flushings following intrauterine deposition of killed bacteria were measured and the effect of immune status on the influx of PMN into the uterine lumen during oestrus was determined . Holstein heifers were immunized with a 270-kDa outer-membrane protein (omp-270) from Haemophilus somnus . During oestrus, immunized heifers (n = 21) received an intrauterine inoculum of either a heat-killed suspension of a homologous strain of H . somnus containing omp-270 (n = 7), a heterologous strain of H . somnus lacking omp-270 (n = 7), or phosphate-buffered saline (n = 7) . Five additional heifers were inseminated with extended bovine semen . Uterine contents were collected in saline lavage immediately before inoculation (t0) and at 6, 24, 48, 72, 96, and 120 h after inoculation . The semen-inoculated heifers were lavaged only at t120 . All groups experienced PMN infiltration which peaked 6 h after inoculation and tended to decline thereafter . Differences were not observed between treatment groups, indicating that neither bacterial inoculation nor immune status was as important in eliciting PMN effusion as the flushing procedure itself.

Am J Vet Res, 1991 Nov, 52(11), 1816 - 20
Characterization and classification of Actinobacillus (Haemophilus) pleuropneumoniae plasmids; Ishii H et al.; Actinobacillus (Haemophilus) pleuropneumoniae plasmids were characterized and classified . They were isolated from A pleuropneumoniae strains different in serotype, year isolated, or location from which isolated . Six of 8 plasmids encoded streptomycin (Sm) and sulfonamide (Su) resistance (SmSu) . One of the other plasmids, pVM105, encoded ampicillin (Ap) resistance and another, pHM0, encoded no drug resistance . All SmSu plasmids were transferred to Escherichia coli strains by transformation . Among them, pABO and pMS260 were 8.1 kb and incompatible with each other; they were stable in E coli . The other SmSu plasmids, pHM1, pVM104, pVM106, and pKD25, were 4.3 kb and did not replicate stably in E coli . The former SmSu plasmids were mobilized in E coli strains by a plasmid RP4, which belonged to incompatibility (Inc) group P, but the latter plasmids were not . Further, each 8.1-kb SmSu plasmid and each 4.3-kb plasmid had the same respective restriction pattern . These results indicated that there were at least 2 types of SmSu plasmids in A pleuropneumoniae . The 2 types were classified in 2 groups: H1(pMS260 and pABO) and H2(pHM1, pVM104, pVM106, and pKD25) . The H1 and H2 plasmids belonged to different Inc groups, and H2 plasmids belonged to a different Inc group from that of pHMO and pVM105.

Jpn J Antibiot, 1991 Nov, 44(11), 1265 - 85
{Laboratory and clinical evaluations of flomoxef sodium in neonates}; Iwai N et al.; Flomoxef sodium (FMOX) was evaluated experimentally and clinically in neonates . 1 . Serum concentrations and urinary excretions of the drug were examined after a bolus intravenous injection at 20 mg/kg to 22 neonates 1-30 days after birth (durations of pregnancy 31-43 weeks, weights at birth 1,650-4,040 g) and 5 infants 50-95 days after birth (durations of pregnancy 33-40 weeks, weights at birth 1,720-3,308 g) . Serum concentrations were 10.8-67.6 micrograms/ml (mean 32.7 +/- 2.8 micrograms/ml) and 25.1-52.0 micrograms/ml (mean 38.9 +/- 4.3 micrograms/ml) in the neonates and the infants, respectively, at their peaks (0.5 hour value), decreased thereafter with half-lives of 0.96-5.59 hours (mean 2.20 +/- 0.26 hours value), and 0.97-1.54 hours (mean 1.22 +/- 0.12 hours value), respectively . Serum levels decreased to 0.2-17.1 micrograms/ml (mean 2.9 +/- 0.6 micrograms/ml) and N.D . -1.1 micrograms/ml (mean 0.4 +/- 0.2 micrograms/ml) after 8 hours, respectively . The urinary recovery rates of the drug in the first 8 hours after administration were 15.0-96.0% (mean 53.7 +/- 4.9%) and 29.9-73.3% (mean 62.4 +/- 9.4%) in the neonates and in the infants, respectively . 2 . FMOX was administered to 78 neonates (durations of pregnancy 31-42 weeks, weights at birth 1,420-3,860 g) in whom bacterial infections were established or suspected, and clinical, bacteriological, and side effects were evaluated . In 47 neonates examined (1 with sepsis, 3 with acute upper respiratory infections, 18 with acute pneumonia, 1 with umbilical infection, 1 with impetigo, 4 with acute urinary tract infections, 1 with acute otitis externa, 1 with periproctal abscess, and 17 with intrauterine infections), the treatment was markedly effective in 41, and effective in 6, with an overall efficacy rate of 100% . The bacterilogical effects of the drug on 3 strains of Staphylococcus aureus, 1 strain of Streptococcus pneumoniae, 1 strain of Streptococcus agalactiae, 9 strains of Escherichia coli, and 2 strains of Haemophilus influenzae which were responsible for these infections were all rated as "eradicated" . Moreover, the drug, administered with or without prophylactic intentions showed complete prophylactic effects in all 27 cases tested . No side effects were observed in any of the patients . Concerning abnormal clinical laboratory results, increases in GOT were noted in 2, eosinophilia in 1, and thrombocytosis in 1, but these abnormalities were invariably mild and the normalized in 1 patient without treatment . The results suggest that FMOX is useful and safe also in neonates.

J Gen Microbiol, 1991 Nov, 137 ( Pt 11), 2571 - 6
Capsulation gene loss and 'rescue' mutations during the Cap+ to Cap- transition in Haemophilus influenzae type b; Brophy LN et al.; Genes for Haemophilus influenzae type b capsule expression are duplicated to form a potentially unstable structure, cap, of directly-repeated chromosomal regions of approximately 17 kb . Capsule-deficient mutants arise in a two-stage process, initiated by rec-dependent reduction of this region from two copies to one . This recombinational event is usually lethal, only about 1/200 surviving to form slow-growing colonies of organisms that continue to synthesize polysaccharide but are defective in its export . A variety of secondary 'rescue' mutations within cap can occur to reduce polysaccharide synthesis and restore normal organism appearance and colony morphology.

J Clin Microbiol, 1991 Nov, 29(11), 2539 - 42
Biotypes of Haemophilus influenzae that are associated with noninvasive infections; Harper JJ et al.; In this study, we examined the biotypes of Haemophilus influenzae strains associated with noninvasive infections in hospitalized patients . Over an 18-month period, a total of 388 strains were isolated from patients of various ages (neonates to the elderly), and the biotypes of the strains were determined . Strains of biotype II accounted for 48% of the isolates; this was followed by strains of biotypes III and I (26 and 16%, respectively) . The remaining 10% of the isolates were made up of strains of biotypes IV, V, VI, and VII . A total of 6% of strains were capsulated . The distribution of biotypes in specimens from the respiratory tract and associated sites was comparable to that obtained in similar investigations, but examination of isolates from neonatal and genital specimens did not support the concept that H . influenzae biotype IV is a major urogenital pathogen . Conflicting results regarding the incidence of certain biotypes in specimens, particularly those from the urogenital tract, may be due to the selection of different subpopulations of patients . Data relating to the specimens were used to evaluate the association between biotype and clinical diagnosis, the presence of other potential bacterial pathogens in the specimens, and the presence of viruses in the specimens . None of the differences in the distribution of biotypes which were examined was statistically significant.

FEMS Microbiol Lett, 1991 Nov 1, 68(1), 27 - 31
Virulence of non-beta-lactamase-mediated ampicillin-resistant Haemophilus influenzae; Rubin LG et al.; We questioned whether strains of ampicillin-resistant, non-beta-lactamase-producing (AmpR NBLP) Haemophilus influenzae with lower affinity penicillin-binding proteins (PBPs) might have altered virulence . The virulence of resistant transformant strains and the susceptible recipient was compared using infant rats . Following intraperitoneal inoculation, there was a significantly lower mortality rate and incidence and magnitude of bacteremia with two of three transformants compared to the recipient strain . Reduced virulence was not associated with greater bactericidal activity of serum or human neutrophils or faster clearance of the transformant following intravenous injection . Heated rat or human plasma supported exponential growth of the recipient, but not the transformant, suggesting deficient in vivo multiplication . We conclude that H . influenzae with altered PBPs are less virulent in an infant rat model which may be related to differences in in vivo growth.

Nurse Pract, 1991 Nov, 16(11), 27, 31 - 6
New protection against Haemophilus influenzae type b infections in infants and young children; Reece SM; Invasive Haemophilus influenzae type b (Hib) infections carry high morbidity and mortality, primarily due to meningitis among infants less than 1 year of age . Two new vaccines, HbOC and PRP-OMP, have been developed and licensed to prevent invasive Hib infections in infants and young children . New recommendations advise clinicians to begin immunization for Hib at 2 months of age and to complete the designated series . This article details the new Hib immunization schedule for all pediatric clients between 2 months and 5 years . Additionally, public-health measures toward the prevention of serious pediatric morbidity and mortality are covered.

J Infect, 1991 Nov, 23(3), 317 - 20
Neonatal septicaemia due to non-capsulate Haemophilus influenzae in three siblings; Cox RA; I report the case of a woman who, in three successive pregnancies, gave birth to premature infants with septicaemia due to non-capsulate Haemophilus influenzae . All three infants displayed characteristic features of the disease . Maternal antenatal and postnatal management is discussed.

J Int Med Res, 1991 Nov-Dec, 19(6), 446 - 50
Azithromycin: an interim analysis; Ball AP; Azithromycin, a novel azalide antibiotic structurally related to erythromycin, has been shown by in vitro studies to have similar activity to erythromycin against Gram-positive pathogens but additionally to have increased activity against some Gram-negative bacteria, notably Haemophilus influenzae . Azithromycin achieves excellent concentrations in tissues, polymorphonuclear leucocytes and alveolar macrophages, and has a prolonged tissue elimination half-life . These properties suggest that short-course, once-daily treatment regimens will be appropriate for a variety of bacterial infections, including those of the respiratory tract, skin and soft tissues . The results of a series of clinical trials using such a regimen are reviewed . It is concluded that azithromycin is clinically and bacteriologically effective in these indications and is well tolerated when compared with regimens using standard antibiotics.

J Bacteriol, 1991 Nov, 173(22), 7361 - 7
Gene localization, size, and physical map of the chromosome of Streptococcus pneumoniae; Gasc AM et al.; A physical map of the Streptococcus (Diplococcus) pneumoniae chromosome, which is circular and 2,270 kbp in circumference, has been constructed . The restriction enzymes ApaI, SmaI, and SacII were used to digest intact chromosomes, and the fragments were resolved by field inversion gel electrophoresis (FIGE) . The digests produced 22, 20, and 29 fragments, respectively . The order of the fragments was deduced from Southern blot hybridization of isolated labeled fragments to separated fragments of the various restriction digests . Genetic markers were correlated with the physical map by transformation of recipient cells with FIGE-isolated DNA fragments derived from genetically marked S . pneumoniae strains . In addition, markers were mapped by the hybridization of cloned genes to FIGE-separated restriction fragments . Six rRNA gene (rrn) clusters were mapped by hybridization to rrn-containing fragments of Haemophilus influenzae.

Infect Immun, 1991 Nov, 59(11), 4221 - 6
Release of leukotriene B4 from human neutrophils after interaction with nontypeable Haemophilus influenzae; Garofalo R et al.; Opsonization of nontypeable Haemophilus influenzae with antibody is critical for the interaction between the organism and human polymorphonuclear leukocytes (PMNs) . Nontypeable H . influenzae opsonized in fresh antibody-positive serum induced the release of 42.5 +/- 17.9 ng of leukotriene B4 per ml from PMNs after 20 min of incubation at 37 degrees C . On the other hand, opsonization of the organisms in fresh antibody-negative serum stimulated the release of significantly smaller amounts of leukotriene B4 by the PMNs . Simultaneous determinations of phagocytosis demonstrated similar patterns of response . A small amount (26.7 +/- 7.6%) of unopsonized nontypeable H . influenzae was phagocytosed by PMNs during 20 min of incubation at 37 degrees C . In contrast, 89.3 +/- 2.0% of nontypeable H . influenzae opsonized in fresh antibody-positive serum was phagocytosed during the same incubation period (P less than 0.001) . Removal of complement through heat inactivation at 56 degrees C for 30 min did not significantly affect phagocytosis . These data suggest that the humoral immune response to nontypeable H . influenzae plays an important role in the inflammatory process and may contribute to the production of middle ear effusions in otitis media.

JAMA, 1991 Oct 23-30, 266(16), 2249 - 52
Bacteriology of acute otitis media in adults; Celin SE et al.; OBJECTIVE.--The objective of this study was to determine the bacteriology of acute otitis media in adults . Although this has frequently been studied in children, no data have recently been reported from adults in the United States . Additionally, information on the prevalence of Haemophilus influenzae as a causative organism in acute otitis media in adults has not been available . DESIGN.--Middle-ear aspirates for cultures were obtained by myringotomy from adults meeting entry criteria . SETTING.--Emergency department, Eye and Ear Hospital of Pittsburgh, Pa . PATIENTS.--Thirty-four patients (volunteer sample) met the eligibility requirements . Exclusion criteria included history of chronic otitis media, recent antibiotic therapy, immunosuppressive illnesses, or prior otologic surgery . INTERVENTION.--Ten days of oral cefuroxime axetil (250 mg) was prescribed . MAIN OUTCOME MEASURES.--Patients were followed closely for at least 6 weeks . Aerobic and anaerobic cultures were incubated and evaluated per the scheduled protocol . RESULTS.--Haemophilus influenzae and Streptococcus pneumoniae were grown on culture of specimens from nine and seven patients (26% and 21%), respectively . Twenty-two percent (2/9) of the H influenzae isolates and the single isolate of Moraxella catarrhalis produced beta-lactamase (9% overall) . CONCLUSIONS.--The present results suggest that, as in children, amoxicillin would be an appropriate first-line agent for empiric therapy of acute otitis media in adults . Antimicrobials inactive against H influenzae (eg, penicillin V, cephalexin, erythromycin, or tetracyclines) are not appropriate for initial therapy . Antimicrobials with efficacy against organisms producing beta-lactamase, such as cefuroxime axetil, which was used to treat the study patients, do not appear to be required for routine initial therapy in adults . However, they would be appropriate when an organism producing beta-lactamase is isolated from the middle ear or when a patient fails to improve rapidly on amoxicillin therapy.

Orv Hetil, 1991 Oct 20, 132(42), 2313 - 4, 2317
{Sensitivity of Hemophilus strains to fluoroquinolones}; Csukas Z et al.; The sensitivity of haemophilus strains isolated from patients freshly were tested by newly produced fluorokinolones with broader antimicrobial activity and excellent pharmacokinetic features . We found a high sensitivity of all haemophilus strains tested by ofloxacin with Resistest method . The minimal inhibitory concentrations in Levinthal bouillon medium ranged between 0,015-0,03 micrograms/ml and the exerted a bactericidal effect . Since these concentrations are only a small portion of the blood and tissue levels of the ofloxacin, therefore the fluorokinolones proved to be effective antibacterial drugs in the therapy of the haemophilus infections.

Am J Dis Child, 1991 Oct, 145(10), 1099 - 103
Endotoxin concentrations in cerebrospinal fluid correlate with clinical severity and neurologic outcome of Haemophilus influenzae type B meningitis; Mertsola J et al.; Endotoxin concentrations were measured in paired samples of cerebrospinal fluid from 38 patients with Haemophilus influenzae type b meningitis . On admission, the median concentration of endotoxin in cerebrospinal fluid was 104 ng/mL and decreased rapidly in follow-up samples . From 17 to 48 hours after admission, 50% of the patients had concentrations of less than 1 ng/mL . Endotoxin concentrations correlated significantly with concentrations of interleukin 1 beta, protein, and glucose in cerebrospinal fluid, duration of secondary fever, and neurologic abnormalities during hospitalization and on follow-up examinations . Twenty-eight percent of patients with endotoxin concentrations of 100 ng/mL or more on admission had long-term complications, compared with none of those with lower endotoxin concentrations (relative risk, 2.31; 95% confidence interval, 1.53 to 3.48) . These results indicate that quantitation of endotoxin in cerebrospinal fluid could be a valuable aid in identifying those children at increased risk of complications during Haemophilus influenzae type b meningitis and provide additional evidence that the Haemophilus influenzae type b meningitis lipo-oligosaccharide is important in the pathogenesis of meningitis.

Antimicrob Agents Chemother, 1991 Oct, 35(10), 1980 - 4
Effect of dexamethasone or HWA-138 in combination with antibiotics in experimental Haemophilus influenzae type b infection; Rodriguez AF et al.; Modulation of the host's inflammatory response in bacterial meningitis may be beneficial . In this study, the effects of dexamethasone and HWA-138, an analog of pentoxifylline, on CSF cultures and cochlear inflammation in an infant rat model of Haemophilus influenzae type b were studied . Five-day-old infant rats were inoculated once intraperitoneally with 1 x 10(4) to 10 x 10(4) CFU of H . influenzae type b (strain 1406) . Twenty-four hours later, infant rats were treated intraperitoneally with one dose of ampicillin (0.1 mg/g of body weight), cefotaxime (0.05 mg/g), or cefuroxime (0.05 mg/g) alone or in combination with one dose of dexamethasone (0.00015 mg/g) or HWA-138 (0.005 mg/g) . Twenty-four hours after treatment with cefuroxime plus dexamethasone, animals had a significantly (P less than or equal to 0.04) greater incidence of bacteremia and meningitis (eight of nine animals) than that in animals of the other treatment groups . Overall, dexamethasone was associated with less inflammation (P less than 0.04) of the cochlear nerve compared with that from antibiotic treatment alone . In this model, when suboptimal antimicrobial therapy is administered, anti-inflammatory agents may be beneficial with respect to reducing cochlear inflammation . However, dexamethasone and cefuroxime lead to a higher rate of positive blood and cerebral spinal fluid cultures than cefuroxime alone.

JAMA, 1991 Oct 9, 266(14), 1960 - 5
Immunoglobulin deficiency and idiotype expression in children developing Haemophilus influenzae type b disease after vaccination with conjugate vaccine . The Collaborative Study Group; Holmes SJ et al.; OBJECTIVE.--Haemophilus influenzae type b (Hib) conjugate vaccines are effective in preventing Haemophilus disease in most children . The reasons why the vaccination fails in some children are unknown . This study investigated host factors in children who developed the disease despite conjugate vaccination . DESIGN, PATIENTS, OUTCOME MEASURES.--A convenience sample of 23 patients in whom Hib disease developed 14 days or more after conjugate vaccination was investigated for the presence of subnormal serum immunoglobulin concentrations and anticapsular antibody responses to Hib disease . We also investigated expression of the Hib idiotype 1 (Hibld-1), a serological marker of a VKII chain that comprises a major portion of the normal variable region repertoire of the antibody response to Hib polysaccharide . The results were compared with those of 149 patients in whom the unconjugated Hib polysaccharide vaccine failed and of 90 unvaccinated patients who developed the disease . RESULTS.--Compared with children in whom the unconjugated polysaccharide vaccination failed, the relative risk of a subnormal serum concentration of IgM, IgA, IgG, and/or IgG2 in the children in whom the conjugate vaccination failed was 4.9 (95% confidence interval {CI}, 1.8 to 14; P less than .003) and of IgG2 was 22 (95% CI, 3.5 to 146; P less than .001) . With the exception of the children with subnormal serum immunoglobulin concentrations, most of the children with conjugate vaccination failure showed normal or high anticapsular antibody responses to the disease, whereas the children with polysaccharide vaccination failure showed impaired responses . The Hibld-1 was expressed by the majority of the children in both vaccination failure groups and of the unvaccinated patients . CONCLUSIONS.--In most patients, vaccination failure is not attributable to lack of expression of the variable region gene encoding Hibld-1 . However, children in whom conjugate vaccination has failed frequently have subnormal serum immunoglobulin concentrations and should be evaluated for immunodeficiency.

Lancet, 1991 Oct 5, 338(8771), 862 - 6
Long-acting chloramphenicol versus intravenous ampicillin for treatment of bacterial meningitis; Pecoul B et al.; In most developing countries, bacterial meningitis (BM) is associated with a high case-fatality rate . The search for a simple, convenient, and inexpensive antibiotic treatment remains a priority . In this study, a non-blinded, multicentre, randomised clinical trial of 528 cases of BM was done in two hospitals in Mali and Niger, between March, 1989, and May, 1990, to see whether a double injection of long-acting chloramphenicol (on admission to hospital and 48 h later) is as effective as a course of intravenous ampicillin (8 days, 4 times a day) . The cumulative case-fatality rate on day 4 (principal end-point) among the chloramphenicol (254 patients) and ampicillin (274) groups were, respectively, 28% and 24.5% (relative risk 1.14, 95% confidence interval 0.86-1.52) . No outbreak occurred during the study period . The hospital case-fatality rate was 33.1% . Main risk factors for death were associated with clinical condition on admission--ie, altered consciousness, convulsions, or dehydration . The case-fatality rates were 13% (21/161) for Neisseria meningitidis, 36.1% (48/133) for Haemophilus influenzae, and 67% (77/115) for Streptococcus pneumoniae . In a multiple logistic regression model, controlling for the differential distribution of potential risk factors (including bacterial species), there was no difference between treatment groups . Our findings suggest that long-acting chloramphenicol is a useful first-line presumptive treatment for BM in high-incidence countriesPublication Types:

	Clinical Trial
	Multicenter Study
	Randomized Controlled Trial

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