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J Antimicrob Chemother, 2000 Jun, 45(6), 851 - 8 Comparison of a 5 day regimen of cefdinir with a 10 day regimen of cefprozil for treatment of acute exacerbations of chronic bronchitis; Fogarty CM et al.; Patients with acute exacerbations of chronic bronchitis were treated with cefdinir 300 mg bd for 5 days or cefprozil 500 mg bd for 10 days in a prospective, randomized, double-blind, multicentre study . Of the 548 patients enrolled, 281 (51%) were evaluable . The clinical cure rates at the test-of-cure visit were 80% (114/142) and 72% (100/139) for the evaluable patients treated with cefdinir and cefprozil, respectively . Respiratory tract pathogens were isolated from 409 (75%) of 548 admission sputum specimens, with the predominant pathogens being Haemophilus parainfluenzae, Haemophilus influenzae, Staphylococcus aureus and Moraxella catarrhalis . The microbiological eradication rates at the test-of-cure visit were 81% (157 of 193 pathogens) and 84% (166 of 198 pathogens) for the evaluable patients treated with cefdinir and cefprozil, respectively . Adverse event rates while on treatment were equivalent between the two treatment groups . The incidence of diarrhoea during therapy was higher for patients treated with cefdinir (17%) than for patients treated with cefprozil (6%) (P < 0.01), but most cases were mild and did not lead to discontinuation of treatment . These results indicate that a 5 day regimen of cefdinir is as effective and safe in the treatment of patients with acute exacerbations of chronic bronchitis as a 10 day regimen of cefprozil. Kansenshogaku Zasshi, 2000 Apr, 74(4), 339 - 44 {A study of bacterial meningitis in Hokkaido between 1994 and 1998}; Sakata H et al.; We evaluated 82 children with bacterial meningitis in 78 institutions in Hokkaido, Japan between 1994 and 1998 . The mean number of cases per year was 16.4 (range, 9 to 30) . A male predominance occurred with 52 males and 30 females (1.7:1) . Median age was 11 months with a range from 1 day to 11 years . Seventy-eight (95%) of the total were less than 5 years old with 55 (67%) less than 2 years old and 45 (55%) less than 1-year old . Four deaths occurred, giving an overall case fatality rate of 4.9% . Sequelae were seen at discharge in 29%, predominantly sensorineural hearing loss, epilepsy and development delay of varying severity . The main causative organisms were Haemophilus influenzae in 49 patients, Streptococcus pneumoniae in 14, Streptococcus agalactiae in 10 and Escherichia coli in 5 . The frequency of poor prognosis was 50% for patients with meningitis due to S . pneumoniae or S . agalactiae compared with 27% for patients with meningitis due to H . influenzae. Eur J Clin Microbiol Infect Dis, 2000 Apr, 19(4), 301 - 4 Prevalence of Haemophilus influenzae carriers in the Catalan preschool population . Working Group on Invasive Disease Caused by Haemophilus influenzae; Fontanals D et al.; This study was designed to determine the prevalence of healthy Haemophilus influenzae carriers in a random sample of the preschool population in Catalonia . Oropharyngeal swabs were collected and cultured on chocolate agar supplemented with 260 microg/ml of bacitracin . Four hundred two of the 734 (54.8%) children studied were detected as Haemophilus influenzae carriers: 7 (0.9%) carried serotype b, 14 (1.9%) serotype e, 6 (0.8%) serotype f, and 375 (51%) carried nontypable strains . The results show that, although the prevalence of Haemophilus influenzae carriers is similar to figures reported from other countries, the prevalence of Haemophillus influenzae serotype b carriers is lower and corresponds with the low incidence of invasive disease observed in the Catalan community. Jpn J Antibiot, 2000 Mar, 53(3), 179 - 83 {In vitro activity of faropenem against beta-lactamase producing clinical isolates}; Nishiyama T et al.; Each 20 strains of beta-lactamase producing methicillin susceptible Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, and Bacteroides fragilis group were used as the test strains . Drug susceptibility of these strains to faropenem (FRPM), cefdinir, cefditoren, cefcapene, cefteram, cefaclor, and ampicillin was determined by an agar dilution method according to the NCCLS guideline M100-S9 . beta-Lactamase activity of the test strains was determined by a spectrophotometric method . In the present study, FRPM was highly active against beta-lactamase-producing strains, and no close correlation was found between the MICs of FRPM for the test strains and their beta-lactamase activities . These results suggest that FRPM has potential in successful application for the treatment of infectious diseases with various types of bacterial pathogens including beta-lactamase producing strains. Pediatrics . 2000 Jun;105(6):E73. Immunization levels and risk factors for low immunization coverage among private practices; Kahane SM et al.; OBJECTIVES: Previous studies have indicated that provider characteristics are an important determinant of immunization coverage . The objectives of this study were to: 1) assess immunization coverage levels among 2-year-old children receiving care in private practices in 3 California counties; and 2) evaluate practice and patient risk factors for low immunization coverage . STUDY DESIGN: Cross-sectional chart review of immunization histories and provider survey of immunization policies . SETTING: Forty-five randomly selected, private medical practices in 3 counties in California . PATIENTS: Children 12 to 35 months old, followed by the participating practices . METHODS: Providers underwent a detailed assessment of their immunization coverage and completed a questionnaire describing their immunization policies and procedures . Immunization data were abstracted from randomly selected medical charts of children 12 to 35 months old . Only patients who met the criteria for active status (>/=2 visits and >/=1 visit during the preceding 18 months) were included in analyses . Immunization coverage levels were calculated and logistic regression was used to estimate the risk of underimmunization associated with different practice and child characteristics . RESULTS: Of the 72 eligible practices that were contacted, 45 participated in the study, yielding a participation rate of 62% . The median immunization coverage of participating offices was 54% (range: 0%-91%) . Multivariate analysis revealed 5 independent risk factors for underimmunization . The strongest predictors were having fewer than 50% active children in the practice and children having fewer than 8 visits to the provider . Other significant predictors were the percentage of patients in the practice on Medicaid, administering diphtheria-tetanus-pertussis 4 at a separate visit from the Haemophilus influenzae type b booster, and practice location . CONCLUSIONS: These data provide new insights into immunization practices in an important clinical setting that has been poorly characterized previously . Immunization coverage levels were found to be low and significant risk factors for underimmunization were identified . Recommendations are made for immunization policy changes and targeting of immunization improvement interventions at practices that may be at risk for low immunization coverage . immunization, vaccination, immunization programs, primary prevention, private practice, child, preschool, pediatrics, family practice. Vet Microbiol, 2000 Jun 12, 74(4), 365 - 76 Apx toxins in Pasteurellaceae species from animals; Schaller A et al.; Pasteurellaceae species particularly of porcine origin which are closely related to Actinobacillus pleuropneumoniae were analyzed for the presence of analogues to the major A . pleuropneumoniae RTX toxin genes, apxICABD, apxIICA and apxIIICABD and for their expression . Actinobacillus suis contains both apxICABD(var.suis) and apxIICA(var . suis) operons and was shown to produce ApxI and ApxII toxin . Actinobacillus rossii contained the operons apxIICA(var.rossii) and apxIIICABD(var.rossii) . However, only the toxin ApxII and not ApxIII could be detected in cultures of A . rossii . The Apx toxins found in A . suis and A . rossi may play a role in virulence of these pathogens . Actinobacillus lignieresii, which was included since it is phylogenetically very closely related to A . pleuropneumoniae, was found to contain a full apxICABD(var.lign.) operon which however lacks the -35 and -10 boxes in the promoter sequences . As expected from these results, no expression of ApxI was detected in A . lignieresii grown under standard culture conditions . Actinobacillus seminis, Actinobacillus equuli, Pasteurella aerogenes, Pasteurella multocida, Haemophilus parasuis, and also Mannheimia (Pasteurella) haemolytica, which is known to secrete leukotoxin, were all shown to be devoid of any of the apx toxin genes and did not produce ApxI, ApxII or ApxIII toxin proteins . However, proteins of slightly lower molecular mass than ApxI, ApxII and ApxIII which showed limited cross-reactions with monospecific, polyclonal anti-ApxI, anti-ApxII and anti-ApxIII were detected on immunoblot analysis of A . equuli, A . seminis and P . aerogenes . The presence of Apx toxins and proteins that imunologically cross react with Apx toxins in porcine Actinobacillus species other than A . pleuropneumoniae can be expected to interfere with serodiagnosis of porcine pleuropneumonia. Acta Paediatr, 2000 Apr, 89(4), 471 - 4 Invasive disease due to Haemophilus influenzae type b during the first six years of general vaccination of Swedish children; Garpenholt O et al.; Since 1992-93 vaccination against Haemophilus influenzae type b (Hib) has been included in the general Swedish childhood vaccination programme . The aim of the present study is to describe the epidemiology, identify and describe vaccine failures and calculate vaccine effectiveness during the first 6 y after introduction of vaccination against Hib . Laboratory reports of blood and cerebrospinal isolates to the Swedish Institute for Infectious Disease Control were used as the source for identifying the patients . Additional information was subsequently obtained from physicians and parents of children who had developed the disease during the study period . Vaccine failures were identified and vaccine effectiveness calculated . During the study period, 152 cases of invasive H . influenzae were identified in the age group 0-14 y . During the 6-y period, 6 true vaccine failures, 6 apparent vaccine failures and 1 possible vaccine failure were found in nearly two million vaccinated child-years . The effectiveness of the Hib vaccination in the birth cohort of children 1993 to 1997 in Sweden was calculated to be 96.1% (95% confidence interval 94.2-97.5) . The study supports earlier studies from several countries that conjugated Hib vaccination introduced in general childhood vaccination programs is effective and substantially decreases suffering from invasive Hib diseases. Indian J Pediatr, 1996 Sep-Oct, 63(5), 583 - 9 Dexamethasone in bacterial meningitis: to use or not to use? Kaul A, Chandwani S. Permanent neurologic disabilities are seen in up to a quarter of survivors of bacterial meningitis despite major improvements in therapy . Experimental studies have demonstrated that most of the pathology in meningitis is mediated by inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1), which are produced by host cells in response to bacterial invasion of the meninges . Dexamethasone has been used in a number of clinical trials to moderate the host response and to improve neurologic outcome of meningitis . Results of six randomized, placebo controlled trials are summarized in this review . Dexamethasone treatment did not lower mortality . Only a moderate, but not a significant reduction in the neurologic and audiologic sequelae was seen in dexamethasone recipients when Haemophilus influenzae type b (Hib) was the causative agent of meningitis . Following routine use of Hib vaccine, meningitis caused by this agent has virtually disappeared in the USA . Hence, findings from these trials may no longer be applicable in countries with high rates of immunization against Hib . Presently, there is little or no evidence showing a benefit of dexamethasone therapy in meningitis caused by S . pneumoniae or N . meningitidis . Global emergence of penicillin and cephalosporin resistant S . pneumoniae has raised new concerns about the use of dexamethasone in pneumococcal meningitis . Since dexamethasone significantly decreases the penetration and concentration of vancomycin and ceftriaxone in the CSF and delays CSF sterilization, adjunctive dexamethasone therapy may increase the risk of treatment failure in meningitis caused by antibiotic resistant pneumococci . An antibiotic combination should be used in the treatment of meningitis caused by antibiotic resistant pneumococci, particularly if dexamethasone is also being administered concurrently. J Antimicrob Chemother, 2000 Apr, 45 Suppl 1, 79 - 85 Comparative in vivo activity of gemifloxacin in a rat model of respiratory tract infection; Berry V et al.; The in vivo efficacy of the novel quinolone gemifloxacin (SB-265805) was examined in a rat respiratory tract infection (RTI) model against four strains of Streptococcus pneumoniae and two strains of Haemophilus influenzae with varying susceptibilities to standard antimicrobial agents . Animals were infected intrabronchially to produce pneumonia and therapy with oral gemifloxacin, amoxycillin-clavulanate, ciprofloxacin, cefuroxime, azithromycin, trovafloxacin, grepafloxacin or levofloxacin was started 24 h after infection . The doses administered were chosen to approximate in the rat the serum or tissue concentrations measured in humans following therapeutic dosing . Therapy continued once- or twice-daily for 3 days, and approximately 17 h after the end of therapy the lungs were excised for bacterial enumeration . Following infection with strains of S . pneumoniae, gemifloxacin produced a 3-5 log reduction in bacterial numbers compared with untreated animals . Gemifloxacin was as effective as amoxycillin- clavulanate, and was as potent or more potent than all other comparators . Notably, the quinolone agents trovafloxacin, ciprofloxacin, grepafloxacin and levofloxacin were significantly less effective (P < 0.01) than gemifloxacin: these agents reduced bacterial numbers by < or =3 log compared with untreated animals . Gemifloxacin produced a marked response against H . influenzae infection, reducing bacterial numbers significantly (P < 0.01) compared with untreated controls . Gemifloxacin was significantly more potent than cefuroxime and azithromycin . None of the other comparator agents was more potent than gemifloxacin . The excellent efficacy seen in these experimental models of RTI with S . pneumoniae and H . influenzae confirms the in vitro activity of gemifloxacin against these organisms . This indicates that gemifloxacin may be of significant benefit in the treatment of RTI. J Antimicrob Chemother, 2000 Apr, 45 Suppl 1, 23 - 7 In vitro antibacterial activity of gemifloxacin and comparator compounds against common respiratory pathogens; Rittenhouse S et al.; This study investigated the in vitro potency of the novel quinolone agent gemifloxacin (SB-265805), in comparison with other quionolones, beta-lactams, macrolides and trimethoprim- sulphamethoxazole, against a panel of common respiratory pathogens . This panel comprised recent clinical isolates of Streptococcus pneumoniae (n = 347), Haemophilus influenzae (n = 256) and Moraxella catarrhalis (n = 184) . Overall, the quinolones were highly active against H . influenzae and were the most potent agents against M . catarrhalis . Gemifloxacin was the most potent quinolone tested against all three species and was four- to 512-fold more potent against pneumococci than trovafloxacin, grepafloxacin, levofloxacin, ciprofloxacin, ofloxacin, gentamicin, cefuroxime, penicillin, ampicillin, clarithromycin, azithromycin or trimethoprim- sulphamethoxazole . Against 19 ofloxacin-intermediate and 52 ofloxacin-resistant strains of S . pneumoniae, gemifloxacin retained activity, and was the only agent tested with MICs of < or =0.5 mg/L . The results of this study demonstrate the excellent in vitro antibacterial activity of gemifloxacin against pathogens commonly associated with respiratory tract infections and suggest that gemifloxacin has significant potential in the treatment of such infections, including those caused by pneumococci considered resistant to other quinolones. J Clin Immunol, 2000 Mar, 20(2), 138 - 49 Vaccination responses to capsular polysaccharides of Neisseria meningitidis and Haemophilus influenzae type b in two C2-deficient sisters: alternative pathway-mediated bacterial killing and evidence for a novel type of blocking IgG; Selander B et al.; Meningitis caused by Neisseria meningitidis serogroup W-135 was diagnosed in a 14-year-old girl with a history of neonatal septicemia and meningitis caused by group B streptococci type III . C2 deficiency type I was found in the patient and her healthy sister . Both sisters were vaccinated with tetravalent meningococcal vaccine and a conjugate Haemophilus influenzae type b vaccine . Three main points emerged from the analysis . First, vaccination resulted in serum bactericidal responses demonstrating anticapsular antibody-mediated recruitment of the alternative pathway . Second, addition of C2 to prevaccination sera produced bactericidal activity in the absence of anticapsular antibodies, which suggested that the bactericidal action of antibodies to subcapsular antigens detected in the sera might strictly depend on the classical pathway . A third point concerned a previously unrecognized type of blocking activity . Thus, postvaccination sera of the healthy sister contained IgG that inhibited killing of serogroup W-135 in C2-deficient serum, and the deposition of C3 on enzyme-linked immunosorbent assay plates coated with purified W-135 polysaccharide . Our findings suggested blocking to be serogroup-specific and dependent on early classical pathway components . Retained opsonic activity probably supported post-vaccination immunity despite blocking of the bactericidal activity . The demonstration of functional vaccination responses with recruitment of alternative pathway-mediated defense should encourage further trial of capsular vaccines in classical pathway deficiency states. Pediatr Infect Dis J, 2000 May, 19(5), 444 - 9 Effect of fever on the serum antibody response of Gambian children to Haemophilus influenzae type b conjugate vaccine; Usen S et al.; BACKGROUND: Acute malaria is a major pediatric problem in developing countries and it is known to be immunosuppressive . METHODS: The serum antibody response to Haemophilus influenzae type b (Hib) conjugate vaccine was investigated in children ages 12 to 30 months with fever associated with malaria, fever associated with other causes or no fever . Groups of 57 children with malaria, 57 children with fever without malaria and 60 healthy children were bled and vaccinated with a single dose of H . influenzae type b capsular polysaccharide-tetanus protein conjugate vaccine . Of these 137 were bled again 1 to 2 months after vaccination . RESULTS: The median antibody titers at baseline were low and similar in the three groups; 77, 65 and 57% of children in the malaria, febrile and healthy groups, respectively, had prevaccination titers of anti-polyribosylribitol phosphate antibodies below 0.15 microg/ml . The median antibody titers after vaccination were 6.3, 7.5 and 23 microg/ml in the malaria, febrile and healthy groups, respectively (P < 0.001, healthy group vs . the two febrile groups) . All the healthy children had protective titers (>0.15 microg/ml) after vaccination, but 11% of the children with malaria and 4% of the other febrile children did not have protective titers . CONCLUSIONS: Anti-polyribosylribitol phosphate titers after Hib vaccination were lower in children with malaria or other febrile illnesses at the time of vaccination than in controls . Fever associated with malaria or other acute illnesses is associated with a diminished response to Hib conjugate vaccine . These findings raise questions about the vaccination of febrile children and indicate the need for further studies in this area. Pediatr Infect Dis J, 2000 May, 19(5), 438 - 44 Antimicrobial resistance of nasopharyngeal isolates of Streptococcus pneumoniae and Haemophilus influenzae from children in the Central African Republic; Rowe AK et al.; BACKGROUND: To assist the Central African Republic (CAR) develop national guidelines for treating children with pneumonia, a survey was conducted to determine antimicrobial resistance rates of nasopharyngeal isolates of Streptococcus pneumoniae (SP) and Haemophilus influenzae (HI) . Secondary purposes of the survey were to identify risk factors associated with carriage of a resistant isolate and to compare the survey methods of including only children with pneumonia vs . including all ill children . METHODS: A cross-sectional survey of 371 ill children was conducted at 2 outpatient clinics in Bangui, CAR . RESULTS: In all 272 SP isolates and 73 HI isolates were cultured . SP resistance rates to penicillin, trimethoprim-sulfamethoxazole (TMP-SMX), tetracycline and chloramphenicol were 8.8, 6.3, 42.3 and 9.2%, respectively . All penicillin-resistant SP isolates were intermediately resistant . HI resistance rates to ampicillin, TMP-SMX and chloramphenicol were 1.4, 12.3 and 0%, respectively . The most common SP serotypes/groups were 19, 14, 6 and 1; 49% of HI isolates were type b . History of antimicrobial use in the previous 7 days was the only factor associated with carriage of a resistant isolate . Resistance rates were similar among ill children regardless of whether they had pneumonia . CONCLUSIONS: Resistance rates were low for antimicrobials recommended by the World Health Organization for children with pneumonia . We recommended TMP-SMX as the first line treatment for pneumonia in CAR because of its low cost, ease of dosing and activity against malaria. Pediatr Infect Dis J, 2000 May, 19(5), 417 - 23 Diminution of the anti-polyribosylribitol phosphate response to a combined diphtheria-tetanus-acellular pertussis/Haemophilus influenzae type b vaccine by concurrent inactivated poliovirus vaccination; Rennels MB et al.; BACKGROUND: Prelicensure studies of Haemophilus influenzae type b vaccines (Hib) and diphtheria-tetanus-acellular pertussis vaccines (DTaP) were evaluated with concurrent oral poliovirus vaccine (OPV) . However, inactivated poliovirus vaccine (IPV) is now recommended . A trial was conducted in which infants received a DTaP and Hib vaccine, separately (+) or combined (/), with either all OPV, all IPV or sequential IPV-OPV for the primary series of vaccinations . METHODS: In this protocol 567 infants were equally randomized to receive one of the following: Reference Arm A, DTaP + Hib + OPV; Treatment Arm B, DTaP/Hib + OPV; Treatment Arm C, DTaP/Hib + IPV at 2 and 4 months and OPV at 6 months; or Treatment Arm D, DTaP/Hib + IPV . antibodies against all administered antigens were measured at 7 months of age . Children with an antibody response to Hib (anti-polyribosylribitol phosphate (anti-PRP) <0.15 microg/ml had an antibody titer repeated after the toddler booster immunization . RESULTS: A significant diminution in the anti-PRP response was observed at 7 months of age in children given two or three doses of IPV concurrently with DTaP/Hib, compared with the groups given OPV . The geometric mean concentration of anti-PRP, percentage of children with > or = 0.15 microg/ml and percentage of children with > or = 1.0 microg/ ml, respectively, were: A, 4.4, 98%, 81%; B, 3.2, 94%, 78%; C, 1.3, 86%, 58% and D, 1.2, 84%, 53% . CONCLUSION: In this trial concurrent IPV appeared to interfere with the anti-PRP response to DTaP/Hib vaccine, suggesting that introduction of new vaccines may require evaluation of immune responses to all concurrently administered vaccines. Br J Gen Pract, 1999 Nov, 49(448), 901 - 2 Vaccine, yes; injection, no: maternal responses to the introduction of Haemophilus influenzae type b (Hib) vaccine; Harrington PM et al.; We used in-depth interviews with 23 mothers of babies aged 1-2 years to explore their response to the addition of Haemophilus influenzae type b (Hib) vaccine to the primary schedule . Acceptability of the vaccine was principally attributable to maternal perceptions as to the severity of meningitis, with a tendency to overestimate the efficacy of the vaccine . Advice from health professionals and the behaviour of peers contributed to its acceptance . Barriers to the uptake of the vaccine included suspicion regarding the newness of the vaccine, a fear of vaccine overload in such young babies, and the distress of two separate injections . There may be a limit to the number of antigens, and particularly the number of injections, acceptable to mothers. Antimicrob Agents Chemother, 2000 Jun, 44(6), 1650 - 4 Increasing bacterial resistance in pediatric acute conjunctivitis (1997-1998); Block SL et al.; We sought to determine the current level of resistance in Haemophilus influenzae and Streptococcus pneumoniae, the primary pathogens of pediatric conjunctivitis . Between January 1997 and March 1998, we prospectively cultured acute conjunctivitis in 250 ambulatory pediatric patients from rural Kentucky whose average age was 24.3 months . In those 250 cases, 106 H . influenzae (42% of the total) and 75 S . pneumoniae (30% of the total) pathogens were isolated, with no growth or no pathogen resulting in 79 cases (32% of the total) . Beta-lactamase was detected in 60 (69%) of 87 tested strains of H . influenzae . Among 65 isolates of S . pneumoniae tested for penicillin susceptibility, 44 (68%) were susceptible, 17 (26%) were resistant, and 4 (6%) were intermediate . Conjunctivitis with acute otitis media was observed in 97 patients (39%), and H . influenzae was recovered in 57% of these 97 cases . As for in vitro activity, ciprofloxacin, ofloxacin, and tetracycline were the most active; and gentamicin, tobramycin, polymyxin B-trimethoprim, and polymyxin B-neomycin were intermediately active . Sulfamethoxazole possessed no activity against either pathogen . Beta-lactamase production was detected in 69% of H . influenzae strains, which still remains the primary causative pathogen of both conjunctivitis and conjunctivitis-otitis syndrome . Penicillin-nonsusceptible S . pneumoniae was observed in 32% of 65 patients with S . pneumoniae conjunctivitis, with most strains being penicillin resistant. Antimicrob Agents Chemother, 2000 Jun, 44(6), 1518 - 23 Morphological changes and lysis induced by beta-lactams associated with the characteristic profiles of affinities of penicillin-binding proteins in actinobacillus pleuropneumoniae; Inui T et al.; Actinobacillus pleuropneumoniae, which was formerly classified in the genus Haemophilus, is a pathogen causing swine pleuropneumonia . We found that aspoxicillin showed strong activity and that meropenem had better lytic activity against this pathogen . In the present study, we for the first time identified penicillin-binding proteins (PBPs) of A . pleuropneumoniae in order to elucidate the relationship between the antibacterial and lytic activities of beta-lactam antibiotics and affinities of the PBPs . The competitive assay using (3)H-labeled benzylpenicillin revealed seven PBPs in A . pleuropneumoniae; they were determined to be PBPs 1a, 1b, 2, 3, 4, 5, and 6, and the molecular masses of these PBPs were estimated to be 92, 80, 76, 72, 50, 44, and 30 kDa, respectively, by comparison with those of Haemophilus influenzae . Our detailed analysis of the affinities of the PBPs of A . pleuropneumoniae and of the bacterial lysis kinetics for several beta-lactam antibiotics revealed that the strong antibacterial activity of aspoxicillin against this strain could be related to the higher affinity of PBP 3 and that preferential inactivation of PBP 1b could cause rapid lysis. J R Coll Physicians Lond, 2000 Mar-Apr, 34(2), 163 - 8 Designing meningitis vaccines; Buttery JP et al.; Conjugate polysaccharide vaccines are a recent intervention to combat the relative inability of young children to mount an effective immune response against encapsulated bacteria, especially Haemophilus influenzae (Hib), Neisseria meningitidis (Nm) and Streptococcus pneumoniae (Sp) . These organisms cause the majority of community acquired septicaemia and meningitis in UK children . Their capsular polysaccharides, important virulence factors in evading phagocytosis, are poorly immunogenic in young children compared to adults . Conjugation, by covalent linking, of the polysaccharide to an immunogenic protein, has been demonstrated for each of these organisms to produce good antibody response to the polysaccharide . Conjugate Hib vaccines have proven effective in reducing Hib meningitis and invasive disease in the countries that have introduced them . Pneumococcal conjugate vaccines have proven effective in preventing invasive disease caused by serotypes contained in the vaccines . Efficacy studies are awaited for meningococcal conjugate vaccines. Infect Immun, 2000 Jun, 68(6), 3362 - 7 Pilus-mediated adherence of Haemophilus influenzae to human respiratory mucins; Kubiet M et al.; Haemophilus influenzae, especially the nontypeable strains, are among the most common pathogens encountered in patients with chronic lung disease and otitis media . We and others have demonstrated that respiratory isolates of nontypeable H . influenzae bind to human mucins, but the mechanism of binding is not entirely clear . We have therefore examined the role of pili in the adherence of both type b and nontypeable H . influenzae to human respiratory mucins . We used isogenic H . influenzae strains with a mutation in the structural gene for pilin (hifA), a laboratory H . influenzae strain transformed with a type b pilus gene cluster (from strain C54), antibodies raised against H . influenzae HifA, and Escherichia coli strains carrying a cloned type b pilus gene cluster (from strain AM30) in these studies . All bacteria lacking HifA or the pilus gene cluster had decreased adherence of piliated H . influenzae to mucins, and Fab fragments of anti-HifA antibodies inhibited the adherence . E . coli strains carrying the cloned type b pilus gene cluster were six to seven times more adhesive than strains carrying the vector . The role of other putative adhesins was not examined and thus cannot be excluded, but these studies support a role for pili in the binding of H . influenzae to human respiratory mucins. Infect Immun, 2000 Jun, 68(6), 3352 - 61 Construction and characterization of Haemophilus ducreyi lipooligosaccharide (LOS) mutants defective in expression of heptosyltransferase III and beta1,4-glucosyltransferase: identification of LOS glycoforms containing lactosamine repeats; Filiatrault MJ et al.; To begin to understand the role of the lipooligosaccharide (LOS) molecule in chancroid infections, we constructed mutants defective in expression of glycosyltransferase genes . Pyocin lysis and immunoscreening was used to identify a LOS mutant of Haemophilus ducreyi 35000 . This mutant, HD35000R, produced a LOS molecule that lacked the monoclonal antibody 3F11 epitope and migrated with an increased mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) . Structural studies indicated that the principal LOS glycoform contains lipid A, Kdo, and two of the three core heptose residues . HD35000R was transformed with a plasmid library of H . ducreyi 35000 DNA, and a clone producing the wild-type LOS was identified . Sequence analysis of the plasmid insert revealed one open reading frame (ORF) that encodes a protein with homology to the WaaQ (heptosyltransferase III) of Escherichia coli . A second ORF had homology to the LgtF (glucosyltransferase) of Neisseria meningitidis . Individual isogenic mutants lacking expression of the putative H . ducreyi heptosyltransferase III, the putative glucosyltransferase, and both glycosyltransferases were constructed and characterized . Each mutant was complemented with the representative wild-type genes in trans to restore expression of parental LOS and confirm the function of each enzyme . Matrix-assisted laser desorption ionization mass spectrometry and SDS-PAGE analysis identified several unique LOS glycoforms containing di-, tri-, and poly-N-acetyllactosamine repeats added to the terminal region of the main LOS branch synthesized by the heptosyltransferase III mutant . These novel H . ducreyi mutants provide important tools for studying the regulation of LOS assembly and biosynthesis. Clin Otolaryngol, 2000 Apr, 25(2), 161 - 8 Children with recurrent episodes of acute otitis media: the effect of local administration of immunoglobulin G on acute otitis media, colonization and turnover of non-encapsulated Haemophilus influenzae in the nasopharynx; Lindberg K et al.; In most children with recurrent episodes of acute otitis media (AOM), tube treatment is successful, but there are those who nevertheless suffer from middle ear infections . The aim of the present study was to ascertain whether local administration of immunoglobulin could reduce the number of episodes of otorrhoea in otitis-prone infants <2 years old who were treated with tubes, or whether it could affect the nasopharyngeal colonization and turnover of bacterial pathogens in the nasopharynx . IgG or placebo were also administered intranasally daily for 6 months to 50 infants, randomized in a double-blind study . An arbitrarily primed polymerase chain reaction (AP-PCR) was used to characterize the different isolates of NTHI (non-encapsulated, non-typable Haemophilus influenzae) . Three infants in the IgG group and six infants in the control group suffered from > or =3 episodes of acute otitis media . No effect on the nasopharyngeal colonization or the turnover of non-encapsulated H . influenzae in the nasopharynx could be detected in either group. Proteins, 2000 Jul 1, 40(1), 86 - 97 Crystal structure of YbaK protein from Haemophilus influenzae (HI1434) at 1.8 A resolution: functional implications; Zhang H et al.; Structural genomics of proteins of unknown function most straightforwardly assists with assignment of biochemical activity when the new structure resembles that of proteins whose functions are known . When a new fold is revealed, the universe of known folds is enriched, and once the function is determined by other means, novel structure-function relationships are established . The previously unannotated protein HI1434 from H . influenzae provides a hybrid example of these two paradigms . It is a member of a microbial protein family, labeled in SwissProt as YbaK and ebsC . The crystal structure at 1.8 A resolution reported here reveals a fold that is only remotely related to the C-lectin fold, in particular to endostatin, and thus is not sufficiently similar to imply that YbaK proteins are saccharide binding proteins . However, a crevice that may accommodate a small ligand is evident . The putative binding site contains only one invariant residue, Lys46, which carries a functional group that could play a role in catalysis, indicating that YbaK is probably not an enzyme . Detailed sequence analysis, including a number of newly sequenced microbial organisms, highlights sequence homology to an insertion domain in prolyl-tRNA synthetases (proRS) from prokaryote, a domain whose function is unknown . A HI1434-based model of the insertion domain shows that it should also contain the putative binding site . Being part of a tRNA synthetases, the insertion domain is likely to be involved in oligonucleotide binding, with possible roles in recognition/discrimination or editing of prolyl-tRNA . By analogy, YbaK may also play a role in nucleotide or oligonucleotide binding, the nature of which is yet to be determined . Ann Epidemiol, 2000 Apr, 10(3), 160 - 8 Immunization coverage among predominantly Hispanic children, aged 2-3 years, in central Los Angeles; Shaheen MA et al.; PURPOSE: To assess the immunization status of young children in a predominantly Hispanic region in and around downtown Los Angeles, and factors associated with complete immunization by age 24 months . METHODS: The information was gathered in a two-stage cluster survey with probability proportionate to estimated size (PPS) sampling of 30 clusters at the first stage, and simple random sampling of a constant number of children at the second stage . Vaccination coverage was determined by a review of the home immunization (HI) card, or of clinic records . RESULTS: Of the 270 sampled children, 91.5% were Hispanic and 6.7% were Black . Home telephone numbers were not available in 24.8% of the homes, and 34.1% reported having no health insurance . Vaccination coverage was over 90% for the first three doses of Diphtheria, tetanus toxoids and pertussis/ diphtheria, tetanus toxoids and acellular pertussis vaccine (DTP/DTaP)/Diphtheria and tetanus toxoids vaccine (DT), first two doses of poliovirus (Polio) vaccine, first dose of measles, mumps and rubella (MMR) vaccine, and first two doses of hepatitis B (Hep B) vaccine . Yet, by age 24 months, only 72.2% of the children had received the combined series of 4:3:1 (i.e., four DTP/DTaP/DT, three Polio, one MMR) . This was further reduced to 64.4% for the combined series of 4:3:1:3:3 (i.e., four DTP/DTaP/ DT, three Polio, one MMR, three Haemophilus influenzae type b (Hib), three Hep B) . Factors associated with completed on-time vaccination were having an HI card available during the interview and being enrolled in Supplemental Nutrition Program for Women, Infants and Children (WIC) . CONCLUSIONS: While vaccination levels for individual antigens were found to be high, more emphasis needs to be placed on getting preschool children vaccinated on-time according to the Recommended Childhood Immunization Schedule. Bull World Health Organ, 2000, 78(3), 364 - 71 Elevated levels of maternal anti-tetanus toxin antibodies do not suppress the immune response to a Haemophilus influenzae type b polyribosylphosphate-tetanus toxoid conjugate vaccine; Panpitpat C et al.; Reported are the effects of elevated levels of anti-tetanus antibodies on the safety and immune response to a Haemophilus influenzae type b polyribosylphosphate (PRP)-tetanus toxoid conjugate (PRP-T) vaccine . A group of Thai infants (n = 177) born to women immunized against tetanus during pregnancy were vaccinated with either a combined diphtheria-tetanus-pertussis (DTP) PRP-T vaccine or DTP and a PRP-conjugate vaccine using Neisseria meningitidis group B outer-membrane proteins as a carrier (PedVax HIB) . Although most infants possessed high titres (> 1 IU/ml) of anti-tetanus antibodies, the DTP-PRP-T combined vaccine engendered an excellent antibody response to all vaccine components . In both vaccine groups > 98% of infants attained anti-PRP antibody titres > or = 0.15 microgram/ml . The geometric mean anti-PRP antibody titres were 5.41 micrograms/ml and 2.1 micrograms/ml for infants immunized with three doses of PRP-T versus two doses of PedVax HIB vaccines, respectively (P < 0.005) . Similarly, the proportion of infants who achieved titres > or = 1 microgram/ml was higher in the PRP-T group (87.8%) than in the group immunized with PedVax HIB (74.2%) (P = 0.036) . A subgroup analysis showed that there was no significant difference in the anti-PRP antibody response for infants exhibiting either < 1 IU of anti-tetanus antibody per millilitre or > or = 1 IU/ml at baseline . These finding indicate that pre-existing anti-carrier antibody does not diminish the immune response to the PRP moiety . All infants possessed protective levels of anti-D and anti-T antibody levels after immunizationPIP: Reported are the effects of elevated levels of anti-tetanus antibodies on the safety and immune response to Haemophilus influenzae type b polyribosylphosphate (PRP)-tetanus toxoid conjugate (PRP-T) vaccine . A group of Thai infants (n = 177) born to women immunized against tetanus during pregnancy were vaccinated with either a combined diptheria-tetanus-pertussis (DTP) PRP-T vaccine or DTP and a PRP-conjugate vaccine using Neisseria meningitidis group B outer-membrane proteins as a carrier (PedVax HIB) . Although most infants possessed high titers (1 IU/ml) of anti-tetanus antibodies, the DTP-PRP-T combined vaccine engendered an excellent antibody response to all vaccine components . In both vaccine groups, 98% of infants attained anti-PRP antibody titers of 0.15 mcg/ml or higher . The geometric mean anti-PRP antibody titers were 5.41 mcg/ml and 2.1 mcg/ml for infants immunized with 3 doses of PRP-T vs . 2 doses of PedVax HIB vaccines, respectively (P 0.005) . Similarly, the proportion of infants who achieved titers of 1 mcg/ml or higher was greater in the PRP-T group (87.8%) than in the group immunized with PedVax HIB (74.2%) (P = 0.036) . A group analysis showed that there was no significant difference in the anti-PRP antibody response for infants exhibiting either less than 1 IU/ml of anti-tetanus antibody or 1 or more IU/ml at baseline . These findings indicate that pre-existing anti-carrier antibody does not diminish the immune response to the PRP moiety . All infants possessed protective levels of anti-D and anti-T levels after immunization . J Commun Dis, 1998 Dec, 30(4), 233 - 6 Bronchopulmonary infection due to Moraxella (Branhamella) catarrhalis at a specialist hospital in Saudi Arabia; Ahmad S; Moraxella (Branhamella) catarrhalis is now considered as one of the most important causative organisms responsible for respiratory tract infection . Specimens of tracheal aspirates from inpatients at King Fahd specialist hospital, Buraidah, Saudi Arabia were collected over a period of 18 months to determine prospectively the frequency of Moraxella catarrhalis and its antimicrobial susceptibility . Moraxella catarrhalis was isolated in pure culture from 3.8% of the tracheal aspirates collected from patients with symptoms of acute respiratory tract infections . It was the third most important pathogen after Haemophilus influenzae and Streptococcus pneumoniae; 76% of the patients had an underlying chronic obstructive pulmonary disease (COPD) . The significance of the findings is discussed. Chemotherapy, 2000, 46 Suppl 1, 15 - 23 Antimicrobial resistance in respiratory tract pathogens: results of an international surveillance study; Thornsberry C et al.; An international surveillance study was performed to assess the resistance patterns among respiratory tract pathogens during the winter of 1997-1998 . The pathogens studied included Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis . The antibiotics tested included five beta-lactams (penicillin, ampicillin, amoxicillin, amoxicillin-clavulanic acid, cefuroxime axetil and ceftriaxone), two macrolides (azithromycin and clarithromycin), one sulfonamide (trimethoprim-sulfamethoxazole), one glycopeptide (vancomycin) and one fluoroquinolone (levofloxacin) . A total of 11,502 isolates were tested from nine countries, using microdilution susceptibility tests as recommended by National Committee for Clinical Laboratory Standards (NCCLS) guidelines . The susceptibility rates varied greatly around the world . Ninety percent of M . catarrhalis isolates produced beta-lactamase, making them resistant to ampicillin . beta-Lactamase production by H . influenzae ranged from 5% in Germany to 34% in the USA (mean 17.5%) . Of the S . pneumoniae isolates, 32.8% had some resistance to penicillin, but this ranged greatly from 7.8% in Germany to 66.5% in France . Penicillin resistance in S . pneumoniae was associated with resistance to other beta-lactams, macrolides and sulfonamides, but not to levofloxacin or vancomycin . All isolates of H . influenzae and M . catarrhalis were susceptible to levofloxacin . Results of this study support the conclusion that these three respiratory tract pathogens are becoming more resistant to selected antimicrobials, and that the level of resistance in these isolates to the antimicrobials varies greatly from one country to another. Nephrol Dial Transplant, 2000 May, 15(5), 619 - 24 Synthesis of immunoglobulins against Haemophilus parainfluenzae by tonsillar lymphocytes from patients with IgA nephropathy; Suzuki S et al.; BACKGROUND: We previously demonstrated glomerular deposition of Haemophilus parainfluenzae (HP) antigens and the presence of IgA antibody against HP antigens in patients with IgA nephropathy (IgAN) . In this report we examine the synthesis of immunoglobulins against HP antigens in tonsillar lymphocytes from patients with IgAN . METHODS: We used tonsillar lymphocytes isolated from the palatine tonsils of 15 patients with IgAN and 16 patients with chronic tonsillitis but without renal disease . We examined lymphocyte proliferation and production of IgA, IgG, and IgM antibodies against HP antigens by measuring thymidine uptake and concentrations of these antibodies in culture supernatants after lymphocyte incubation with HP antigens by ELISA . RESULTS: Lymphocytes from patients with IgAN showed a significantly higher stimulation index (SI) on exposure to HP antigens (thymidine incorporation in tonsillar lymphocytes exposed to HP (c.p.m.)/ thymidine incorporation in unstimulated tonsillar lymphocytes (c.p.m.)) than did controls (P=0 . 0015) . Lymphocytes from patients with IgAN also showed a significantly higher IgA SI (concentrations of IgA against HP antigens in supernatants from HP-stimulated lymphocytes/IgA against HP antigens in supernatants from unstimulated tonsillar lymphocytes) than did controls (P=0.0004) . We found positive correlations between concentrations of IgA and IgG antibodies, between IgA and IgM antibodies, and between IgG and IgM antibodies against HP antigens after HP stimulation . CONCLUSIONS: Our results suggest that HP antigens stimulate tonsillar T and B lymphocytes in patients with IgAN and that these patients have polyclonal activation of lymphocytes against HP antigens, with isotype switching of antibody production from IgM to IgA. Arch Intern Med, 2000 May 8, 160(9), 1294 - 300 Azithromycin vs cefuroxime plus erythromycin for empirical treatment of community-acquired pneumonia in hospitalized patients: a prospective, randomized, multicenter trial; Vergis EN et al.; OBJECTIVE: To compare the efficacy and safety of azithromycin dihydrate monotherapy with those of a combination of cefuroxime axetil plus erythromycin as empirical therapy for community-acquired pneumonia in hospitalized patients . METHODS: Patients were enrolled in a prospective, randomized, multicenter study . The standard therapy of cefuroxime plus erythromycin was consistent with the American Thoracic Society, Canadian Community-Acquired Pneumonia Consensus Group, and Infectious Disease Society of America consensus guidelines . The doses were intravenous azithromycin (500 mg once daily) followed by oral azithromycin (500 mg once daily), intravenous cefuroxime (750 mg every 8 hours), followed by oral cefuroxime axetil (500 mg twice daily), and erythromycin (500-1000 mg) intravenously or orally every 6 hours . Randomization was stratified by severity of illness and age . Patients who were immunosuppressed or residing in nursing homes were excluded . RESULTS: Data from 145 patients (67 received azithromycin and 78 received cefuroxime plus erythromycin) were evaluable . Streptococcus pneumoniae and Haemophilus influenzae were isolated in 19% (28/145) and 13% (19/145), respectively . The atypical pathogens accounted for 33% (48/145) of the etiologic diagnoses; Legionella pneumophila, Chlamydia pneumoniae, and Mycoplasma pneumoniae were identified in 14% (20/ 145), 10% (15/145), and 9% (13/145), respectively . Clinical cure was achieved in 91% (61/67) of the patients in the azithromycin group and 91% (71/78) in the cefuroxime plus erythromycin group . Adverse events (intravenous catheter site reactions, gastrointestinal tract disturbances) were significantly more common in patients who received cefuroxime plus erythromycin (49% {30/78}) than in patients who received azithromycin (12% {8/67}) (P<.001) . CONCLUSIONS: Treatment with azithromycin was as effective as cefuroxime plus erythromycin in the empirical management of community-acquired pneumonia in immunocompetent patients who were hospitalized . Azithromycin was well tolerated. Laryngoscope, 2000 May, 110(5 Pt 1), 779 - 86 Hearing preservation with labyrinthine ablation in otitis media; Antonelli PJ et al.; OBJECTIVES: Iatrogenic fenestration of the inner ear in the presence of otitis media is commonly associated with permanent hearing loss . Hearing can generally be preserved when the vestibular labyrinth is ablated in a controlled manner in noninflamed ears . The purpose of this study was to examine the feasibility of hearing preservation with violation of the inner ear in the presence of middle ear inflammation . STUDY DESIGN: Prospective and controlled animal model . METHODS: Otitis media was induced bilaterally in pigmented guinea pigs with transtympanic injection of Streptococcus pneumoniae, nontypeable Haemophilus influenzae, or formalin-killed nontypeable H influenzae . Two to 4 days after injection, the horizontal canal of one ear was transected and sealed . Hearing was tested before and after labyrinthine ablation . RESULTS: Otitis media was induced in all ears . Bacterial cultures were positive in 19 of 20 S pneumoniae-injected ears, and in 10 of 16 nontypeable H influenzae-injected ears . One week after surgery, elevation of click thresholds (> 15 dB) was encountered in none of the fenestrated or unfenestrated S pneumoniae-infected ears, in two of six unfenestrated and three of six fenestrated nontypeable H influenzae-infected ears, and in one of five killed-nontypeable H influenzae-injected ears both with and without fenestration . CONCLUSIONS: These data suggest that ablation of a semicircular canal in the presence of middle ear inflammation or infection does not necessarily lead to profound sensorineural hearing loss . Hearing loss associated with iatrogenic violation of the semicircular canals may be more dependent on factors other than the presence of nonspecific middle ear inflammation. Arch Otolaryngol Head Neck Surg, 2000 May, 126(5), 625 - 9 Resistant bacteria in the adenoids: a preliminary report; McClay JE; OBJECTIVE: To determine the incidence of resistant bacteria in adenoid cultures from children with and without middle ear disease and rhinosinusitis symptoms . DESIGN: Children meeting the requirement for tympanostomy tube placement underwent an adjuvant adenoidectomy for symptoms of adenoid hypertrophy or recurrent rhinosinusitis . Adenoid tissue and coexisting middle ear fluid, if present, were cultured . SETTING: Tertiary referral children's hospital with community-based satellite clinics . PATIENTS: Forty-six patients ranging in age from 1 to 11 years (68% <3 years) with recurrent or persistent otitis media and symptoms of adenoid hypertrophy or rhinosinusitis (study patients) underwent tympanostomy tube placement and adenoidectomy with culture of the adenoids and middle ear effusions . Eighteen patients with adenoid hypertrophy without ear disease or rhinosinusitis were used as controls . INTERVENTIONS: Tympanostomy tube placement and adenoidectomy . MAIN OUTCOME MEASURES: Presence or absence of resistant bacteria . RESULTS: Resistant bacteria were found in cultures of the adenoids in 56% (26/46) of the study group compared with 22% (4/18) of the control patients (P<.02) . Also, strains of Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis were found in cultures from 78% (36/ 46) of the study group, compared with 44% (8/18) of those from the control group (P<.01) . Resistant isolates were found in 65% (23/35) of the S . pneumoniae, 37% (18/49) of the H . influenzae, and 100% (19/19) of the M . catarrhalis cultures from the adenoids or middle ear spaces . CONCLUSION: Resistant bacteria are present in significant amounts in the adenoids of children with middle ear disease and rhinosinusitis symptoms compared with patients without those diseases or symptoms. Can J Vet Res, 2000 Apr, 64(2), 88 - 95 A 24-kDa cloned zinc metalloprotease from Actinobacillus pleuropneumoniae is common to all serotypes and cleaves actin in vitro; Garcia-Cuellar C et al.; Actinobacillus pleuropneumoniae causes pleuropneumonia in swine . This bacterium secretes proteases that degrade porcine hemoglobin and IgA in vitro . To further characterize A . pleuropneumoniae proteases, we constructed a genomic library expressed in Escherichia coli DH5alpha, and selected a clone that showed proteolytic activity . The recombinant plasmid carries an 800-base pair A . pleuropneumoniae gene sequence that.codes for a 24-kDa polypeptide . A 350-base pair PstI fragment from the sequence hybridized at high stringency with DNA from 12 serotypes of A . pleuropneumoniae, but not with DNA from Actinobacillus suis, Haemophilus parasuis, Pasteurella haemolytica, Pasteurella multocida A or D, or E . coli DH5alpha, thus showing specificity for A . pleuropneumoniae . The expressed polypeptide was recognized as an antigen by convalescent-phase pig sera . Furthermore, a polyclonal antiserum developed against the purified polypeptide recognized an A . pleuropneumoniae oligomeric protein in both crude-extract and cell-free culture media . This recombinant polypeptide cleaved azocoll, gelatin, and actin . Inhibition of the proteolytic activity by diethylpyrocarbonate suggests that this polypeptide is a zinc metalloprotease. Rinsho Byori, 2000 Jan, Suppl 111, 75 - 83 {Detection methods for drug-resistant bacteria in routine examination--BLNAR}; Misawa S et al.; The characteristics of resistance, trend of prevalence and current status of beta-lactamase-negative, ampicillin-intermediate or -resistant(BLNAR) strains of Haemophilus influenzae are summarized by our retrospectively analyzed data . The mechanism of this type of ampicillin-resistance is due to altered penicillin-binding proteins(PBPs) . Standardized susceptibility tests may differentiate ampicillin-resistant, beta-lactamase-producing strains from beta-lactamase-negative, ampicillin-susceptible strains(BLNAS), but may not differentiate some strains of BLNAR from those of BLNAS . In the cases of serious infections, such as meningitis due to H . influenzae both beta-lactamase activity and ampicillin susceptibility should be confirmed by the MIC procedure. Rinsho Byori, 2000 Jan, Suppl 111, 17 - 25 {Drug-resistant bacteria of current topics and their resistance mechanisms--PRSP and BLNAR}; Ubukata K; The prevalence of resistant isolates for beta-lactam antibiotics have been rapidly increasing in Streptococcus pneumoniae and Haemophilus influenzae . These strains having resistant elements are called penicillin-resistant S . pneumoniae(PRSP) and beta-lactamase-negative ampicillin-resistant H . influenzae(BLNAR) . The mechanism of resistance was identified as the reduction of penicillin-binding proteins(PBPs) affinities as the target of beta-lactams . In PRSP, pbp1a, pbp2x, and pbp2b encoding PBP1A, -2X, and -2B enzymes, respectively, were altered . In contrast, mutations in the ftsI gene encoding PBP3A were only clarified in BLNAR . Characteristics of the resistance caused by PBPs alterations are a low-level resistance that decrease bactericidal action. Microbiol Immunol, 2000, 44(2), 143 - 8 Molecular characterization and functional analysis of a secA gene homolog in Actinobacillus actinomycetemcomitans; Novak KF et al.; Results of Southern blot analyses and polymerase chain reaction revealed that the Gram-negative pathogen, Actinobacillus actinomycetemcomitans, harbored DNA homologous to the secA gene of Escherichia coli . In E . coli, the secA gene product is essential for translocation of proteins across the inner membrane via the Sec system . This A . actinomycetemcomitans secA homolog was cloned and its nucleotide sequence determined . Amino acid sequence analysis of the cloned gene revealed significant homology to the SecA proteins of Haemophilus influenzae, E . coli, Caulobacter crescentus and Bacillus subtilis . Although the cloned gene did not complement a temperature sensitive mutation in the E . coli secA gene, strains harboring the cloned gene did produce a protein that cross-reacted with anti-SecA antibody . In addition, the cloned gene did restore sensitivity to sodium azide in an E . coli azide mutant . These data support the hypothesis that A . actinomycetemcomitans may use a system similar to the Sec system of E . coli to transport proteins across the cytoplasmic membrane, but suggest that the A . actinomycetemcomitans gene product may require genera-specific Sec proteins to complement some Sec mutations in E . coli. Przegl Epidemiol, 1999, 53(3-4), 271 - 9 {Introduction to the epidemiology of disease caused by Haemophilus influenzae}; Zielinski A; This review article characterizes Haemophilus influenzae bacteria and presents basic clinical syndromes caused by it . It informs about sources and pathways of Haemophilus influenzae infection and gives basic comparative data on its epidemiology in different countries, and also different ethnic and social groups. Acta Otorrinolaringol Esp, 2000 Jan-Feb, 51(1), 19 - 24 {Descriptive study of infectious ear disease in relation to summer}; Burgos Sanchez A et al.; A descriptive study was made of infectious ear disease (including diffuse otitis externa, otomycosis, acute-on-chronic otitis media, and superinfection of a radical mastoidectomy cavity) in relation to changes of weather and habits in summer . During the months of June, July, and August 1996, 179 patients were evaluated in the emergency room of the Alicante General University Hospital, Spain . Average patient age at presentation was 30.52 (+/- 20.08) years and 56% were men . The most frequent disease was diffuse otitis externa (78%) followed by acute-on-chronic otitis media (12%), otomycosis (8%), and superinfection of a radical mastoidectomy cavity (2%) . The most frequently involved microorganisms were Pseudomonas aeruginosa in diffuse otitis externa, Aspergillus niger and Candida in otomycosis, Escherichia coli, Haemophilus influenzae, Proteus mirabilis, and Staphylococcus aureus in acute-on-chronic otitis media . Patients were treated by cleaning detritus and secretions, usually followed by topical antibiotics for a maximum period of one week. FEMS Immunol Med Microbiol, 2000 Jun, 28(2), 129 - 32 Interaction of clinical isolates of nonencapsulated Haemophilus influenzae with mammalian extracellular matrix proteins; Bresser P et al.; The adherence of clinical isolates of nonencapsulated Haemophilus influenzae strains from patients with chronic bronchitis to distinct immobilized extracellular matrix components was determined . With selected strains the induction of plasmin formation by these isolates was studied . The strains could be divided into two groups: strains that showed a very high level of adherence to laminin and type I collagen, as well as adhesion to fibronectin and strains that showed only a moderate level of adhesion to laminin and a low level of adhesion to fibronectin . Plasmin formation was demonstrated for three out of eight isolates . Persisting and nonpersisting strains did not differ quantitatively or qualitatively with respect to the level of adhesiveness to the distinct matrix proteins and in their ability to induce plasmin formation. FEMS Immunol Med Microbiol, 2000 Jun, 28(2), 105 - 11 Stimulation of bacterial adherence by neutrophil defensins varies among bacterial species but not among host cell types; Gorter AD et al.; Adherence of Haemophilus influenzae to bronchial epithelial cells is enhanced by neutrophil defensins, which are released from activated neutrophils during inflammation {Gorter et al . (1998) J . Infect . Dis . 178, 1067-1078} . In this study, we showed that the adherence of H . influenzae to various epithelial, fibroblast-like and endothelial cell types was significantly enhanced by defensins (20 microg ml(-1)) . Defensins stimulated also the adherence of Moraxella catarrhalis, Neisseria meningitidis and nonencapsulated Streptococcus pneumoniae to the NCI-H292 cell line . In contrast, defensins did not affect the adherence of Pseudomonas aeruginosa, encapsulated S . pneumoniae, Escherichia coli and Staphylococcus epidermidis . These results suggest that the defensin-enhanced adherence might support the adherence and possibly persistence of the selected bacterial species using the respiratory tract as port of entry. Microb Pathog, 2000 May, 28(5), 301 - 12 Characterization of a DNA region containing 5'-(CAAT)(n)-3' DNA sequences involved in lipooligosaccharide biosynthesis in Haemophilus somnus; McQuiston JH et al.; Repetitive tetranucleotide sequences of 5'-(CAAT)(n)-3' have been identified at the 5' end of an open reading frame (ORF) named lob1 from Haemophilus somnus strain 738 . Based on sequence analysis, lob1 has 59% DNA homology to lex2B, which is involved in lipooligosaccharide (LOS) biosynthesis in H . influenzae . We now report that the number of 5'-CAAT-3' repeats in lob1 varied from 31-35, but that 94% of colonies contained 33 repeats of 5'-CAAT-3' downstream of two potential start codons, as determined by DNA sequence analysis of the 5'-CAAT-3' region from individual colonies . If transcription began with the start codon closest to the 5'-CAAT-3' repeats, a protein of 34.5 kDa would be encoded when 33 repeats were present . However, we could not establish a correlation between the number of 5'-CAAT-3' repeats in lob1 with a specific LOS electrophoretic profile or reactivity with two LOS monoclonal antibodies, indicating multiple genes control LOS phase variation in H . somnus . Complementation of strain 129Pt with lob1 containing 33 5 '-CAAT-3' repeats in shuttle vector pLS88 resulted in transformants 129Pt(pLSlob1-33A) and 129Pt(pLSlob1-33B), both of which demonstrated the same altered LOS electrophoretic profile . Unlike strain 129Pt, both transformants underwent limited LOS phase variation, which correlated with variation in the number of 5'-CAAT-3' repeats in pLSlob1-33 . Nanoelectrospray-mass spectrometry of O-deacylated LOS indicated that transformant 129Pt(pLSlob1-33A) LOS was composed of a different distribution of glycoforms than LOS of the parent strain . The ratio of glucose to galactose changed from 1:2 in strain 129Pt LOS to 2:1 in transformant 129Pt(pLSlob1-33A) LOS, as determined by gas chromatography-mass spectrometry . Nuclear magnetic resonance spectroscopy confirmed and extended these observations . Transformant 129Pt(pLSlob1-33A) was constitutively more reactive in colony immunoblotting to polyclonal antiserum made to purified strain 738 LOS, and was more susceptible to complement-mediated killing in the presence of anti-738 LOS serum than parent strain 129Pt . Based on these results, Lob1 appears to be a phase variable galactosyl transferase involved in LOS biosynthesis in H . somnus . Mol Cell Probes, 2000 Apr, 14(2), 61 - 9 Rapid diagnosis of acute pyogenic meningitis by a combined PCR dot-blot assay; Balganesh M et al.; A multiplex PCR was employed to amplify unique conserved sequences of DNA from the pathogens Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae from cerebrospinal fluid samples of patients suffering from acute pyogenic meningitis . The accurate identification of the PCR amplified product was achieved by hybridizing dot-blots of the PCR products to probes which were specific, biotinylated internal sequences of the amplified target DNA . Detection of the hybrids was done in a colour reaction using streptavidin-alkaline phosphatase conjugate and BCIP/NBT substrates . The entire protocol took only 7 h for the correct identification of the pathogen present in clinical samples of cerebrospinal fluid . The sensitivity and specificity were >95% . Indian J Pediatr, 1999 Nov-Dec, 66(6), 831 - 6 Blood culture and respiratory syncytial virus identification in acute lower respiratory tract infection; Miranda-Novales G et al.; Even though the incidence of pneumonia in developed and developing countries is similar, the mortality is five times higher in developing countries . This study aimed to determine the prevalence of bacteremia in children with acute lower respiratory tract infection (LRTI) and relative contribution of respiratory syncytial virus (RSV) . One hundred and one children under five years of age who attended a primary care level clinic with diagnosis of acute LRTI, were enrolled . Diagnosis and management of pneumonia were done according to the WHO guidelines . Two blood cultures were drawn at the time of admission . A nasopharyngeal sample was taken for detection of RSV by indirect immunofluorescence . Blood cultures were positive for pathogenic bacteria (Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus) in three patients . The detection for RSV was positive in 24 patients (23.7%) . The clinical and radiographic presentations were not significantly different between patients with and without RSV (p > 0.05) . RSV is a common cause of LRTI in children younger than five years old . Blood cultures are not commonly positive in outpatients with acute LRTI . The practice of obtaining blood cultures in primary and secondary care clinics is not useful to guide the treatment of patients with community-acquired pneumonia. Rev Neurol, 1999 Aug 16-31, 29(4), 311 - 5 {Prognosis of bacterial meningitis}; Pena JA et al.; OBJECTIVES: To review the literature on the risk factors for bacterial meningitis (BM) and evaluate these factors in children diagnosed as having BM in the Paediatric Department of the University Hospital of Maracaibo between 1996 and 1998 . PATIENTS AND METHODS: We made a retrospective study of children diagnosed as having BM in the University of Maracaibo . We evaluated different factors related to BM . RESULTS: From 1 January 1996 to 31 December 1998 a total of 152 children were diagnosed as having bacterial meningitis; 69.7% were boys and 30.3% were girls . The commonest causal germ was Haemophilus influenzae . Disorders of sensation (42.7%) and signs of meningism (32.8%) were the most frequent neurological alterations . The main laboratory findings were leucocytosis (51.3%), thrombocytosis (49.3%), pleocytosis (70.3%), cerebrospinal fluid protein (49.3%) and low cerebrospinal fluid glucose (72.8%) . Twelve patients (7.5%) died . Of this group, 10 were under one year of age and had septic shock . CONCLUSIONS: BM represents a major group of hospital admissions in everyday paediatric practice . Although the mortality has decreased, an increased risk of sequelas must be borne in mind . Clinico-neurological examination on admission and simultaneous analysis of laboratory investigations allows identification of prognostic indicators of morbidity and mortality. J Antimicrob Chemother, 2000 May, 45(5), 655 - 62 Antibiotic resistance in respiratory tract isolates of Haemophilus influenzae and Moraxella catarrhalis collected from across Canada in 1997-1998; Zhanel GG et al.; Between September 1997 and November 1998 respiratory tract isolates of Haemophilus influenzae (n = 1352) and Moraxella catarrhalis (n = 428) were collected by 18 Canadian medical centres . beta-Lactamase was produced by 24.0 and 94.2% of H . influenzae and M . catarrhalis isolates, respectively . Resistance rates for H . influenzae were highest for ampicillin (24.0%), trimethoprim/sulphamethoxazole (13 . 7%), loracarbef (6.1%) and cefaclor (4.2%), and </= 1% for amoxycillin/clavulanate, cefotaxime, cefprozil, cefixime, imipenem, ciprofloxacin, levofloxacin, grepafloxacin, trovafloxacin and chloramphenicol . M . catarrhalis resistance rates, derived using NCCLS breakpoint criteria for Haemophilus spp., were </= 1% for all antibiotics tested except ampicillin (49.5%) and trimethoprim/sulphamethoxazole (1.6%). J Antimicrob Chemother, 2000 May, 45(5), 599 - 604 Epidemiological studies of large resistance plasmids in Haemophilus; Leaves NI et al.; The distribution of large conjugative Haemophilus influenzae plasmids in the nasopharyngeal haemophili of a group of people and in a large collection of 541 H . influenzae type b (Hib) isolates was studied . A newly developed PCR-based assay was used to detect the plasmids . The target sequences were chosen from sequence analysis of part of p1056, a large multiresistance plasmid isolated from a clinical Hib isolate, 1056 . Fifty-nine per cent of people were found to carry beta-lactamase-positive (beta-lac(+)), ampicillin-resistant (ampR) haemophili with detectable plasmid sequences . Of these, 83% were in Haemophilus parainfluenzae and 17% were in H . influenzae . In the collection of 541 Hib, antibiotic resistance {beta-lac(+)ampR, beta-lac(+)ampR plus tetracycline resistance (tetR) or tetR} was highly correlated with large plasmids . It was found that 2.3% of the isolates contained large cryptic plasmids (i.e . these isolates were susceptible to antibiotics) . The distribution of plasmids between invasive and carried Hib did not differ significantly (25 of 245 and 23 of 276, respectively) . Isolates with large plasmids occur at high frequency in the nasopharynx of the normal human population and consist of two populations in Hib, one associated with specific antibiotic resistance traits and the other cryptic . These plasmids do not appear to influence the invasiveness of Hib. Cochrane Database Syst Rev . 2000;(2):CD001958. Haemophilus influenzae oral vaccination against acute bronchitis; Foxwell AR et al.; OBJECTIVES: To assess the effects of an oral whole cell nontypeable Haemophilus influenzae (NTHi) vaccine in protecting against recurrent episodes of bronchitis . SEARCH STRATEGY: We searched the Cochrane trials register, MEDLINE, Extramed, ISI Current Contents, Carl Uncover and contacted investigators of the studies . SELECTION CRITERIA: Randomised trials comparing the effects of an oral monobacterial NTHi vaccine on patients with recurrent exacerbations of bronchitis were included when there was overt matching of the vaccine and placebo groups on clinical grounds . DATA COLLECTION AND ANALYSIS: Two reviewers extracted data and assessed trial quality independently from original records and publications for incidence and severity of bronchitis episodes and carriage rate of nontypeable Haemophilus influenzae in the upper respiratory tract every three months following vaccination . MAIN RESULTS: Six trials were included in the study with a total of 440 participants . Oral vaccination using a monobacterial whole cell killed nontypeable Haemophilus influenzae significantly reduced the incidence of bronchitic episodes at 3 months (Weighted Mean Difference {WMD} 6.694; 95% confidence interval {CI} 6.963 - -6.424; p < 0.01) and 6 months (WMD 4.496; 95% CI 4.664 - -4.327; p < 0.01) following vaccination . The effect diminished by 9 months . The severity of exacerbations in the treatment group was likewise reduced by 58% at 3 months (Peto OR = 0 . 42; 95% CI 0.16 1.13), and 65% at 6 months (Peto OR = 0.35; 95% CI 0 . 16 0.75) following vaccination . REVIEWER'S CONCLUSIONS: Vaccination, in the autumn, of patients with recurrent exacerbations of bronchitis reduced the number and severity of exacerbations over the winter months . A large clinical trial to assess longer term prognosis needs to be completed. Br J Biomed Sci, 1999, 56(4), 239 - 46 Meningitis antigen detection: interpretation of agglutination by ultrasound-enhanced latex immunoassay; Sobanski MA et al.; Detailed instructions for performance and interpretation of ultrasound-enhanced latex agglutination tests for the rapid identification of bacteria causing meningitis are described . This recently developed technique, which enhances the sensitivity of most latex immunoagglutination assays, has been studied mainly in the context of detection of antigens of meningitis-causing bacteria . The test concentrates on the Wellcogen bacterial antigen kit (Murex Diagnostics Ltd) that contains five latex suspensions specific for Haemophilus influenzae type b, Neisseria meningitidis ACYW135, N . meningitidis B/Escherichia coli K1, Streptococcus group B and Streptococcus pneumoniae . Light photomicrographs of positive agglutination are shown . Particular attention is paid to the appearance of the latex in negative control samples following exposure to ultrasound . Guidance is given on interpretation and assessment in clinical samples. Diagn Microbiol Infect Dis, 2000 May, 37(1), 1 - 4 Performance of a multiplex PCR for the determination of Haemophilus influenzae capsular types in the clinical microbiology laboratory; Gonin P et al.; To improve tools for the surveillance of invasive H . influenzae in the context of the drastic decrease of type b infections following the implementation of vaccination, a two-step PCR technique was developed to detect the capsule and type specific regions of H . influenzae . The technique of Falla et al (1994) was modified to amplify in a first step the capsule and type b regions by multiplex PCR . For non-b capsulated strains, the type a, c, d, e, and f loci were afterward detected simultaneously by an optimized touch-down PCR technique . An internal control of extraction and amplification (16S rDNA) was included for both PCR techniques . Overall, this technique was shown to perform as efficiently or better than the slide agglutination without risks of interpretation errors . Of the 138 H . influenzae strains tested, seven that had given doubtful results by the agglutination technique were unequivocally typed by PCR. Otolaryngol Head Neck Surg, 2000 May, 122(5), 696 - 700 Dynamics of nasopharyngitis in children; Brook I et al.; PURPOSE: Our goal was to characterize the dynamics and bacterial interaction of the aerobic and anaerobic flora of nasal discharge of children at different stages of uncomplicated nasopharyngitis . Methods And Patients: Serial semiquantitative nasopharyngeal (NP) and quantitative nasal discharge (ND) cultures were taken every 3 to 5 days from 20 children in whom purulent discharge eventually developed (group 1), and a single culture was obtained from a group of 20 who had only clear discharge (group 2) . RESULTS: Aerobic and anaerobic bacteria were isolated from all NP cultures . Bacterial growth was present in 8 (40%) NDs of group 2 . Only 7 (35%) of the clear NDs of group 1 showed bacterial growth; the number increased to 14 (70%) at the mucoid stage and 20 (100%) at the purulent stage . It declined to 6 (30%) at the final clear stage . The number of species and total number of organisms increased in the NDs of group 1 . Group 1 patients had higher recovery rates of Streptococcus pneumoniae and Haemophilus influenzae in their NP cultures than group 2 patients (P < 0.05) . During the purulent stage, Peptostreptococcus species were isolated in 15 (75%), Fusobacterium species in 10 (50%), Prevotella species in 9 (45%), H influenzae in 8 (40%), S pneumoniae in 6 (30%), and beta-hemolytic streptococci in 5 (25%) of group 1 NDs . This was higher than their recovery in the clear stages of both groups and the mucoid stage of group 1 . A total of 8 organisms capable of interfering with the growth of potential pathogens were isolated from the NPs of group 1, as compared with 35 from group 2 (P < 0.001) . CONCLUSIONS: The development of purulent nasopharyngitis is associated with the pre-existing presence of potential pathogens and the absence of interfering organisms. Semin Hematol, 2000 Apr, 37(2), 177 - 85 The role of blood group antigens in infectious diseases; Rios M et al.; The medical literature contains a large number of publications attempting to correlate blood groups with disease . Many of these reports are poorly documented and have limited scientific validity . Only a few agents, such as malaria parasites and parvovirus B19, infect red blood cells (RBCs) and precursors . Most other agents use RBCs as carriers to the target tissue . There is an excess of blood group A individuals among cancer patients compared with normal individuals; malignancy has also been associated with the Lewis antigen . Plasmodium vivax only enters RBCs when the Fy6 Duffy protein is present . Certain Escherichia coli organisms will only attach to epithelial cells carrying P or Dr blood group antigens . The P antigen Is also the receptor for parvovirus B19 . Le(b) appears to be the receptor for Helicobacter pylori in gastric tissue . The high frequency blood group antigen AnWJ is the receptor for Haemophilus influenzae . Knowledge of the functions of RBC surface molecules Is expanding and the ability to generate experimental animals devoid of certain molecules will clarify their physiological role. Plasmid, 2000 May, 43(3), 235 - 9 Analysis of the complete nucleotide sequence of the tetracycline-resistance transposon Tn10; Lawley TD et al.; An analysis of the complete nucleotide sequence of the composite tetracycline-resistance transposon Tn10 (9147 bp) from the Salmonella typhi conjugative plasmid R27 is presented . A comparison of the protein sequences from IS10-right and IS10-left transposases has identified four amino acid differences . These residues appear to play an important role in normal transposase function and may account for the differences in exhibited transposition activities . The tetracycline determinants encoded by this version of Tn10 share >99% identity with those of Tn10(R100), demonstrating the conservation that exists between these transposons . A previously uncharacterized approximately 3000-bp region of Tn10 contains four putative open reading frames . One of these open reading frames shares 55% identity with the glutamate permease protein sequence from Haemophilus influenzae although it was unable to complement an Escherichia coli glutamate permease mutant, with which it shares 51% identity . The three remaining putative open reading frames are arranged as a discrete genetic unit adjacent to the glutamate permease homolog and are transcribed in the opposite direction . Two of these open reading frames are homologous with Bacillus subtilis proteins of unknown functions while the other has no homologs in the database . The presence of an aminoacyl-tRNA synthetase class II motif in one of these open reading frames in combination with the glutamate permease homolog allows us to postulate that this region of Tn10 could once have played a role in amino acid metabolism . Pediatr Infect Dis J, 2000 Apr, 19(4), 378 - 82 Clinical significance of resistant organisms in otitis media; Dagan R; BACKGROUND: Otitis media is an important health care problem of childhood . The bacteriology of otitis media comprises three main pathogens: Streptococcus pneumoniae, nontypable Haemophilus influenzae and Moraxella catarrhalis . Although the prevalence of resistant strains varies geographically and temporally, antimicrobial resistance is widespread and increasing . RESISTANCE TO ANTIBIOTIC DRUGS: Among the risk factors for development of resistance in otitis media are antimicrobial use, young age, day-care attendance and prior hospitalization . The increasing rate of resistance to antibiotic drugs is associated with a decreased rate of successful eradication of pathogens from middle ear fluid, which is associated with clinical failure . A bacteriologic cure rate of 80 to 85% is observed for S . pneumoniae and nontypable H . influenzae when serum concentrations exceed the MIC for 40 to 50% of dosing interval . Comparative trials indicate that some of the beta-lactams can achieve bacteriologic eradication in acute otitis media, although major differences in outcome exist among agents based on pathogen, beta-lactamase status and MIC values . ANTIBIOTIC CHOICE: Overall the choice of antibiotics for treatment of otitis media should take into consideration their in vitro activity against the locally prevalent organisms, especially resistant organisms, and results obtained from studies in which bacteriologic outcome was used as the endpoint. Vaccine, 2000 Jun 1, 18(24), 2625 - 35 The introduction of new vaccines into developing countries II . Vaccine financing; Mahoney RT et al.; The development of new vaccines for important childhood diseases presents an unparalleled opportunity for disease control but also a significant problem for developing countries: how to pay for them . To help address this problem, the William H . Gates Foundation has established a Global Fund for Children's Vaccine . In this paper, we discuss the allocation of this and other similar funds, which we call Global Funds . We propose that allocation of the Global Funds to individual countries be guided in part by a Vaccine Procurement Baseline (VPB) . The VPB would set a minimum of 0.01% of gross national product (GNP) as an amount each developing country would devote to its own vaccine procurement . When this amount is not sufficient to procure the vaccines needed by a developing country, the Global Funds would meet the shortfall . The amount required of donors to maintain the Global Funds would be about $403 million per year for both existing EPI vaccines as well as for a hypothetical group of five new vaccines costing $0.50 per dose and requiring three doses per child . Including program costs, poor developing countries currently spend about 0.13% of GNP on EPI immunizations . In contrast, the United States, as one example donor country, spends about 0.035% of GNP for childhood immunization including several new vaccines . This paper analyzes the Global Funds requirements for hepatitis B and Haemophilus influenzae type b (Hib) vaccines . After a ramp-up period, needier countries would eventually require about $62 million for hepatitis B and $282 million for Hib at current prices . Various additional criteria could be used to qualify countries for participation in the Global Funds. Lab Anim, 1999 Jul, 33(3), 288 - 94 Immunohistological characterization of leukocytes in the lungs of healthy mice and after bacterial intratracheal infection; Heitmann S et al.; Leukocytes in the peripheral lung parenchyma of mice have not been characterized histologically during bacterial infection . The aim of this study was to investigate (a) the immunohistological characteristics of healthy murine lungs and (b) the cell kinetics during acute inflammation . BALB/c and MF1 mice were examined; as well as transgenic mice with the gene defect of cystic fibrosis (CF) in the airways as an animal model for this disease . MF1 mice served as controls for the transgenic animals . Lavaged and perfused lungs were snap frozen . B and T lymphocytes, CD4+ and CD8+ cells, dendritic cells, neutrophils and a subset of macrophages were enumerated on cryostat lung sections . The lung tissue and bronchoalveolar lavage (BAL) of BALB/c mice, infected intratracheally with Haemophilus influenzae type b (Hib), were studied at different time points after infection . In the lungs of healthy mice, including CF mice, the largest population was that of T cells, CD4+ cells being always more frequent than CD8+ cells . During acute inflammation the number of neutrophils in the lung parenchyma and BAL increased strongly within the first hours after bacterial instillation and reached baseline levels within one week . This study provides a semi-quantitative analysis of immunocompetent cells in normal and infected murine lung tissue . Differences in cell numbers are found between different strains . Moreover, the cellular reaction during Hib infection in mouse lungs is dominated by neutrophils, as expected in a primary immune response . In uninfected CF mice the numbers and distribution of immune cells in the lung tissue are normal, indicating that the cellular defense is adequate. Can J Microbiol, 2000 Apr, 46(4), 358 - 62 Comparative evaluation of conjugate vaccines in the Haemophilus influenzae infection model; Miyazaki S et al.; We used a murine model of Haemophilus influenzae type b (Hib) infection to analyze the immunologic response to two commercially available PRP conjugate vaccines (HbOC, PRP-T) . The mortality rate in mice infected with a large dose of the bacteria after vaccination with HbOC or PRP-T at two and three doses was significantly lower than in non-vaccinated mice and mice vaccinated by one dose . Furthermore, for infections caused by a small bacterial dose, the mortality rate in mice vaccinated with one, two, or three doses was significantly lower than in non-vaccinated mice . The induction level of anti-PRP antibodies, especially IgG, in serum of mice vaccinated by two or three doses was higher than in those vaccinated with a single dose . Our results indicate that the dose of vaccine influences its efficacy in protecting against Hib infection . Our results also showed a lack of difference between two different PRP conjugate vaccines. Can J Microbiol, 2000 Apr, 46(4), 325 - 32 Detection of the Na(+)-translocating NADH-quinone reductase in marine bacteria using a PCR technique; Kato S et al.; To examine the distribution of the Na(+)-translocating NADH-quinone reductase (Na(+)-NQR) among marine bacteria, we developed a simple screening method for the detection of this enzyme . By reference to the homologous sequences of the Na(+)-NQR operons from Vibrio alginolyticus and Haemophilus influenzae, a pair of primers was designed for amplification of a part of the sixth ORF (nqr6) of the Na(+)-NQR operon . When PCR was performed using genomic DNA from 13 marine bacteria, a 0.9-kbp fragment corresponding to nqr6 was amplified in 10 strains . Although there were three PCR-negative strains phylogenetically, based on the sequence of the 16S rRNA, these were placed far from the PCR-positive strains . No product was observed in the case of nonmarine bacteria . The nucleotide and predicted amino acid sequences of nqr6 were highly conserved among the PCR-positive marine bacteria . A phylogenetic analysis of marine bacteria, based on nqr6 sequencing, was performed. Drugs, 2000 Mar, 59(3), 477 - 85 Treatment of sexually transmitted bacterial diseases in pregnant women; Donders GG; Testing for and treating sexually transmitted diseases (STDs) in pregnant women deserves special attention . Treatment possibilities are limited because of potential risks for the developing fetus, and because effects can differ in pregnant compared with non-pregnant women, re-infection may be missed because of the intrinsic delicacy of contact-tracing during pregnancy and because pregnant women are more reluctant to take the prescribed medication in its full dose, if at all . However, the devastating effects of some of these genital infections far outweigh any potential adverse effects of treatment . Although active syphilis has become a rarity in most Western countries, it is still prevalent in South America, Africa and South-East Asia . Benzathine benzylpenicillin (2.4 million units once or, safer, twice 7 days apart) is the treatment of choice, although patients with syphilis of longer standing require 3 weekly injections as well as extensive investigation into whether there has been any damage due to tertiary syphilis . Despite declining rates of gonorrhea, the relative rate of penicillinase-producing strains is increasing, especially in South-East Asia . The recommended treatment is intramuscular ceftriaxone (125 or 250 mg) or oral cefixime 400 mg . Despite good safety records after accidental use, fluoroquinolones are contraindicated during pregnancy . An alternative to a fluoroquinolone in pregnant women with combined gonorrhea and chlamydial infection is oral azithromycin 1 or 2 g . Azithromycin as a single 1 g dose is also preferable to a 7 day course of erythromycin 500 mg 4 times a day for patients with chlamydial infection . Eradication of Haemophilus ducreyi in patients with chancroid can also be achieved with these regimens or intramuscular ceftriaxone 250 mg . Trichomonas vaginalis, which is often seen as a co-infection, has been linked to an increased risk of preterm birth . Patients infected with this parasite should therefore received metronidazole 500 mg twice daily for 7 days as earlier fears of teratogenesis in humans have not been confirmed by recent data . Bacterial vaginosis is also associated with preterm delivery in certain risk groups, such as women with a history of preterm birth or of low maternal weight . Such an association is yet to be convincingly proven in other women . The current advice is to treat only women diagnosed with bacterial vaginosis who also present other risk factors for preterm delivery . The treatment of choice is oral metronidazole 1 g/day for 5 days . The possible reduction of preterm birth by vaginally applied metronidazole or clindamycin is still under investigation . In general, both test of cure and re-testing after several weeks are advisable in most pregnant patients with STDs, because partner notification and treatment are likely to be less efficient than outside pregnancy and the impact of inadequately treated or recurrent disease is greater because of the added risk to the fetus . Every diagnosis of an STD warrants a full screen for concomitant genital disease . Most ulcerative genital infections, as well as abnormal vaginal flora and bacterial vaginosis, increase the sexual transmission efficiency of HIV, necessitating even more stringent screening for and treating of STD during pregnancy. Vaccine, 2000 May 22, 18(23), 2584 - 91 Differing serologic responses to an haemophilus influenzae type b polysaccharide-neisseria meningitidis outer membrane protein conjugate (PRP-OMPC) vaccine in australian aboriginal and caucasian infants - implications for disease epidemiology; Guthridge S et al.; This study compared Hib antibody responses to a single lot of PRP-OMPC vaccine given at 2, 4 and 12 months to 57 Aboriginal infants in rural areas of the Northern Territory and 56 Caucasian infants in Sydney, Australia . The Aboriginal infants had lower levels of antibody in cord blood (P>0.05), which were significantly lower (P<0.02) by 2 months of age . Antibody responses to one or two doses of vaccine, measured at 4 and 12 months of age, were similar but the geometric mean titre following the booster dose in Aboriginal infants was significantly lower (1.98 vs . 6.04 mcg/ml, P = 0.002) . Low preimmunisation antibody is consistent with the early onset of Hib disease in Aboriginal infants before immunisation . Lower responses to boosting could correlate with persistence of Hib colonisation in indigenous populations. Southeast Asian J Trop Med Public Health, 1998 Dec, 29(4), 772 - 8 The new DTPw-HBV-Hib combination vaccine can be used at the who schedule with a monovalent dose of hepatitis B vaccine at birth; Bravo L et al.; An open, randomized, clinical trial was conducted in order to assess the reactogenicity and immunogenicity of DTPw-HBV and Haemophilus influenzae type b (Hib) vaccines when given either as a mixed administration or as separate concomitant injections using the WHO schedule at 6, 10 and 14 weeks of age, following a dose of HBV at birth . There were no clinically relevant differences in the immune response to any component between the mixed and separate administrations . In fact the anti-tetanus GMTs were significantly higher (p=0.002) in mixed administration (3.9 IU/ml) compared with the separate administration (1.9 IU/ml) . However although all subjects achieved anti-PRP titers > or = 0.15 microg/ml, higher anti-PRP GMTs were seen in the group receiving the separate administration . Importantly, the addition of Hib did not adversely alter the reactogenicity profile of DTPw-HBV . This report which demonstrates that this novel combination can be used in WHO recommended schedule. Arq Neuropsiquiatr, 2000 Mar, 58(1), 141 - 5 IgG2 immunodeficiency: association to pediatric patients with bacterial meningoencephalitis; Escobar-Perez X et al.; An IgG subclass deficiency is often associated with bacterial infections . We studied four pediatric patients suffering from meningoencephalitis, two of them due to Streptococcus pneumoniae and two due to Haemophilus influenzae type b . Simultaneous diagnostic serum and cerebrospinal fluid samples were taken during income . The four subclasses of IgG and albumin were quantified in both biologic fluids by radial immunodiffusion . Very low levels of seric IgG2 with non detectable cerebrospinal fluid IgG2 were found in the patients . No intrathecal IgG subclass synthesis was found in two patients . One patient with S . pneumoniae had IgG3 intrathecal synthesis . Intrathecal IgG1, IgG3 and IgG4 synthesis was found in one patient suffering from H . influenzae according with reibergrams . Substitutive therapy with intravenous gammaglobulin was given to the patients as part of the treatment. Antimicrob Agents Chemother, 2000 May, 44(5), 1342 - 5 Multicenter surveillance of antimicrobial resistance of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in Taiwan during the 1998-1999 respiratory season; Hsueh PR et al.; A susceptibility surveillance study of 276 isolates of Streptococcus pneumoniae, 301 of Haemophilus influenzae, and 110 of Moraxella catarrhalis was carried out from November 1998 to May 1999 in Taiwan . High rates of nonsusceptibility to penicillin (76%), extended-spectrum cephalosporins (56%), azithromycin (94%), clarithromycin (95%), and trimethoprim-sulfamethoxazole (TMP-SMX) (65%) for S . pneumoniae isolates and high rates of nonsusceptibility to amoxicillin (58%) and TMP-SMX (52%) for H . influenzae isolates were found . Higher percentages of S . pneumoniae isolates nonsusceptible to aminopenicillins, extended-spectrum cephalosporins, macrolides, and TMP-SMX were observed among penicillin-intermediate and -resistant isolates . All quinolones tested were active in vitro against these three organisms. Turk J Pediatr, 1999 Oct-Dec, 41(4), 421 - 7 Safety, tolerability and immunogenicity of a Haemophilus influenzae type b vaccine containing aluminum phosphate adjuvant administered at 2, 3 and 4 months of age; Kanra G et al.; The primary aim of this study was to assess the tolerability and immunogenicity of a new Haemophilus influenzae type b (Hib)/AlPO4 (CHIRON, SpA) vaccine, in two-month-old healthy infants . Twenty-three subjects were enrolled and administered the new Hib vaccine containing AlPO4 adjuvant at two, three and four months of age concomitantly with diphtheria-pertussis-tetanus (DPT) and hepatitis B vaccines according to the local program . Children were observed for 30 minutes after each immunization for any immediate local and systemic reactions . An active surveillance for side effects was performed on the 2nd and 7th days following each immunization by telephone . Families also filled out diaries for the first seven days . From the 2nd day to the next immunization only data about adverse events necessitating a physician's visit or about serious adverse events were collected . Blood samples were obtained before the first immunization and one month after the third dose for evaluation of anti-polyribosylribitol phosphate (PRP) antibody response . Local reactions at the Hib site were mild and less frequent compared to those observed at the DPT site . Systemic reactions noted after the three immunizations were fever in 70 percent, irritability in 48 percent, persistent crying in 26 percent, change in eating habits in 22 percent, diarrhea in 17 percent, sleepiness in 17 percent, vomiting in 9 percent, and unusual crying in 4 percent of the cases . There was no serious adverse event . One hundred percent and 95 percent of children achieved an anti-PRP antibody response over 0.15 microg/ml and 1.0 microg/ml, respectively . The geometric mean titer was 15 microg/ml and the geometric mean ratio 84 . It was concluded that the new (Hib)/AlPO4 vaccine is safe and well tolerated, and induced a good PRP antibody response in healthy two-month-old infants. Infect Immun, 2000 May, 68(5), 3007 - 9 Characterization of ferrochelatase (hemH) mutations in Haemophilus influenzae; Schlor S et al.; Haemophilus influenzae lacks most of the biosynthetic enzymes for hemin synthesis . However, the organism has retained ferrochelatase activity, which we identified to be encoded by a hemH-homologous gene . In this report we characterize the growth physiology conferred by hemH mutations under infection and laboratory conditions. Infect Immun, 2000 May, 68(5), 2804 - 7 Role of lipopolysaccharide phase variation in susceptibility of Haemophilus influenzae to bactericidal immunoglobulin M antibodies in rabbit sera; Erwin AL et al.; The effect of phase variation of lipopolysaccharide (LPS) structure on the susceptibility of Haemophilus influenzae to complement-dependent killing by normal human sera and normal rat sera has been described previously . The phase-variable structure phosphorylcholine (ChoP) confers susceptibility to human serum, since ChoP on the bacterial cell surface binds to serum C-reactive protein and activates complement . In contrast, expression of galalpha1,4gal, a second phase-variable epitope that is also found on human glycoconjugates, confers resistance to human serum . We studied the role of phase variation of these structures in the susceptibilities of H . influenzae KW20 (Rd) and a clinical isolate of nontypeable H . influenzae to killing by rabbit sera, which often possess naturally acquired complement-dependent bactericidal activity for unencapsulated H . influenzae . Expression of ChoP increased the resistance of strain KW20 to killing by bactericidal rabbit sera . In contrast, the serum resistance of a clinical isolate, H233, was unaffected by ChoP expression but was reduced by galalpha1,4gal expression . The rabbit sera with bactericidal activity (but not the nonbactericidal sera) all contained immunoglobulin M (IgM) antibodies able to bind to the surface of H . influenzae bacteria, as detected by flow cytometry, and contained IgM antibodies to LPS purified from strain KW20 . Preincubation of sera with LPS reduced their bactericidal activity . Bactericidal activity was recovered quantitatively in an IgM-enriched fraction of sera . It is concluded that naturally occurring bactericidal activity for unencapsulated H . influenzae is largely due to IgM antibodies directed against phase-variable structures of the LPS. Infect Immun, 2000 May, 68(5), 2756 - 65 Passive transfer of antiserum specific for immunogens derived from a nontypeable Haemophilus influenzae adhesin and lipoprotein D prevents otitis media after heterologous challenge; Kennedy BJ et al.; We recently determined that passive transfer of serum directed against a synthetic peptide called LB1 or a recombinant fusion protein immunogen {LPD-LB1(f)(2,1,3)} could prevent otitis media after challenge with a homologous nontypeable Haemophilus influenzae (NTHI) isolate . NTHI residing in the nasopharynx was rapidly cleared from this site, thus preventing it from ascending the eustachian tube and inducing otitis media in chinchillas compromised by an ongoing viral upper respiratory tract infection . While LB1 is based solely on one NTHI adhesin, the latter immunogen, LPD-LB1(f)(2,1,3), was designed to incorporate two NTHI antigens shown to play a role in the pathogenesis of otitis media; lipoprotein D (LPD) and the P5-homologous fimbrin adhesin . The design of LPD-LB1(f)(2,1,3) also accommodated for the recently demonstrated existence of three major groupings, based on amino acid sequence diversity, in the third surface-exposed region of P5-fimbrin . LPD-LB1(f)(2,1,3) was thus designed to potentially confer broader protection against challenge by diverse strains of NTHI . Chinchillas were passively immunized here with serum specific for either LB1 or for LPD-LB1(f)(2,1,3) prior to challenge with a member of all three groups of NTHI relative to diversity in region 3 . The transferred serum pools were also analyzed for titer, specificity, and several functional activities . We found that both serum pools had equivalent ability to mediate C'-dependent killing and to inhibit adherence of NTHI strains to human oropharyngeal cells . When passively transferred, both serum pools significantly inhibited the signs and incidence of otitis media (P </= 0.01) induced by any of the three challenge isolates . Despite providing protection against disease, the ability of these antisera to induce total eradication of NTHI from the nasopharynx was not equivalent among NTHI groups . These data thus suggested that while early, complete eradication of NTHI from the nasopharynx was highly protective, reduction of the bacterial load to below a critical threshold level appeared to be similarly effective. Infect Immun, 2000 May, 68(5), 2692 - 7 Mucosal immune responses to meningococcal group C conjugate and group A and C polysaccharide vaccines in adolescents; Zhang Q et al.; Previous studies in children have shown that Haemophilus influenzae type b (Hib) polysaccharide conjugate vaccines can reduce nasopharyngeal carriage of H . influenzae and provide herd immunity and suggest that this effect is mediated through mucosal antibodies . As this phenomenon may operate in other invasive bacterial infections which are propagated by nasopharyngeal carriage, mucosal antibody responses to meningococcal C conjugate and A/C polysaccharide vaccines were investigated . A total of 106 school children aged 11 to 17 years were randomized to receive a single dose of either conjugate or polysaccharide vaccine in an observer-blind study . Before and at 1, 6, and 12 months after immunization, samples of unstimulated saliva were collected and assayed by enzyme-linked immunosorbent assay for group C polysaccharide-specific immunoglobulin A (IgA), IgA1, IgA2 and secretory component, IgG antibodies, and total IgG and IgA . A subset of serum samples were also assayed for specific IgA and IgG antibodies . The concentrations of specific IgA and IgG in saliva were expressed both as nanograms per milliliter and as nanograms per microgram of total IgA or IgG . One month after immunization, significant increases in antibody titers (both IgA and IgG) were observed in saliva in both groups . There were significant subsequent falls in antibody titers by 6 months . Anti-meningococcal C-specific secretory component and IgA antibody titers were closely correlated (r = 0.85, P < 0.001), but there was no significant correlation between salivary and serum IgA titers, suggesting that IgA antibodies are locally produced . Significant correlation was found between salivary and serum IgG titers (r = 0.52, P < 0.01), suggesting that salivary IgG may be serum derived . Compared with polysaccharide vaccine, the conjugate vaccine induced significantly higher salivary IgG responses (P < 0.05), although there were no significant differences between salivary IgA responses to the two vaccines . The conjugate vaccine induced greater salivary IgG responses than a polysaccharide vaccine . Both vaccines induced significant salivary IgA antibodies . Further studies are needed to establish the functional significance of these mucosal responses. Infect Immun, 2000 May, 68(5), 2630 - 7 Identification and genetic characterization of Haemophilus influenzae genetic island 1; Chang CC et al.; The type b capsule of pathogenic Haemophilus influenzae is a critical factor for H . influenzae survival in the blood and the establishment of invasive infections . Other pathogenic factors associated with type b strains may also play a role in invasion and sustained bacteremia, leading to the seeding of deep tissues . The gene encoding haemocin is the only noncapsular gene found to be specific to type b strains until now . Here we report the discovery of an approximately 16-kb genetic locus, HiGI1, that is present primarily in type b strains . Pulsed-field gel electrophoresis and Southern hybridization were used to map this new locus between secG (HI0445) and fruA (HI0446), which are contiguous in Rd, a nonpathogenic derivative of a serotype d strain . It is inserted at the 3' end of tRNA(4)(Leu) and has regions whose G+C content differs from the average genomic G+C content of H . influenzae . An integrase gene, which encodes a CP4-57 like integrase, is located downstream of tRNA(4)(Leu) . Hybridization probes based on the sequences within the HiGI1 locus have been used to screen 61 H . influenzae strains (2 type a, 22 type b, 2 type c, 1 type d, 3 type e, 7 type f, and 21 nontypeable H . influenzae {NTHi}) from our collection . This HiGI1 locus exists in all 22 type b strains and two NTHi strains and is likely to have been acquired by an ancestral type b strain. Infect Immun, 2000 May, 68(5), 2602 - 7 Evaluation of an isogenic major outer membrane protein-deficient mutant in the human model of Haemophilus ducreyi infection; Throm RE et al.; Haemophilus ducreyi expresses 2 OmpA homologs, designated MOMP and OmpA2, whose genes are arranged in tandem on the chromosome . Northern blot analysis indicated that momp and ompA2 are transcribed independently . Sequences of the momp open reading frame (ORF) lacking the transcriptional start site were amplified by PCR, and an Omega-Km2 cassette was ligated into the ORF . A plasmid containing this construction was electroporated into H . ducreyi 35000HP, and an isogenic MOMP-deficient mutant (35000HP-SMS2) was generated by allele exchange . In Southern blotting, 35000HP-SMS2 contained one copy of the Omega-Km2 cassette in momp . 35000HP and 35000HP-SMS2 had similar outer membrane protein (OMP) and lipooligosaccharide profiles and growth rates except for up-regulation of a putative porin protein in the mutant . Five subjects were inoculated with three doses of live 35000HP-SMS2 on one arm and two doses of live 35000HP and one dose of a heat-killed control on the other arm in a double-blind escalating dose-response trial . Pustules developed at 7 of 10 sites inoculated with 35000HP and at 6 of 15 sites inoculated with 35000HP-SMS2 (P = 0.14) . 35000HP and 35000HP-SMS2 were recovered at similar rates from daily surface cultures and semiquantitative cultures . The data suggest that expression of MOMP is not required for pustule formation by H . ducreyi in the human model of infection. Infect Immun, 2000 May, 68(5), 2525 - 34 Identification of a Haemophilus influenzae 5'-nucleotidase protein: cloning of the nucA gene and immunogenicity and characterization of the NucA protein; Zagursky RJ et al.; We report on the identification of a surface-exposed, highly conserved, immunogenic nontypeable Haemophilus influenzae (NTHi) protein, which elicits cross-reactive bactericidal antibodies against NTHi . The protein was extracted from NTHi strain P860295 with KSCN and purified; it migrated as a single band on a sodium dodecyl sulfate-polyacrylamide gel with an apparent molecular mass of 63 kDa . Mouse antiserum generated against the purified protein was reactive on whole-cell enzyme-linked immunosorbent assay (ELISA) with seven NTHi strains and type b Eagan and Whittier strains and exhibited bactericidal activity to homologous and heterologous NTHi strains . However, the protein is made in small amounts in NTHi as corroborated by immunoelectron microscopy . To further study this protein, we cloned, sequenced, and expressed it recombinantly in Escherichia coli . The recombinant protein is localized in the periplasm of E . coli and has been purified to homogeneity . Both the recombinant and native proteins possess 5'-nucleotidase activity; hence, the protein has been called NucA . Mouse antiserum directed against the recombinant NucA protein was reactive on Western immunoblots and whole-cell ELISA with all H . influenzae strains tested including Eagan and was bactericidal for two heterologous strains tested . The antiserum also resulted in a log reduction in bacteremia, in an infant-rat protection study with H . influenzae type b as the challenge strain . These features suggest that NucA is a potential subunit vaccine candidate against NTHi disease. Am J Health Syst Pharm, 2000 Apr 1, 57(7), 663 - 8 Pharmacotherapy of acute sinusitis in children; Temple ME et al.; The pharmacotherapeutic options for acute sinusitis in children are reviewed . Acute sinusitis occurs more frequently in children than in adults . The diagnosis is based primarily on clinical signs and symptoms . Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are the organisms most frequently implicated . A variety of antimicrobials have FDA-approved labeling for use in the treatment of sinusitis . In randomized, controlled clinical trials identified in a MEDLINE search for the period from 1966 to 1999, amoxicillin had efficacy similar to that of amoxicillin-clavulanate, azithromycin, cefuroxime, and clarithromycin in treating acute sinusitis in children . Azithromycin was effective as a three-day course of treatment . Amoxicillin and cefuroxime are better tolerated than most antibiotics; azithromycin and clarithromycin are also well tolerated . Amoxicillin-clavulanate tends to cause more gastrointestinal symptoms than amoxicillin and is more expensive . Azithromycin is more expensive than amoxicillin but less expensive than other broad-spectrum antimicrobials . Amoxicillin remains the drug of first choice for treating acute sinusitis in children . It has been found to be as effective as other broad-spectrum agents, better tolerated, and less expensive. Chest, 2000 Apr, 117(4), 1017 - 22 Bacterial pneumonia in hospitalized patients with HIV infection: the Pulmonary Complications, ICU Support, and Prognostic Factors of Hospitalized Patients with HIV (PIP) Study; Afessa B et al.; STUDY OBJECTIVES: To describe the causative organisms and factors associated with bacterial pneumonia and to assess its impact on the outcome of hospitalized patients with HIV . DESIGN: Prospective, observational . SETTING: A university-affiliated medical center . METHODS: We included 1,225 consecutive hospital admissions, from April 1995 through March 1998, of 599 adults with HIV . We collected data on APACHE II (acute physiology and chronic health evaluation II) score, leukocyte and CD4+ lymphocyte counts, length of hospital stay, ICU admission rate, and case-fatality rate . Chest radiographs and laboratory results were reviewed . The presence of bacterial pneumonia was noted . RESULTS: Bacterial pneumonia was diagnosed in 111 hospitalizations (9%): 80 (72%) were community-acquired infections . The CD4+ lymphocyte count was lower (median, 38 vs 66/microL, p = 0.0027), APACHE II score higher (17 vs 13, p < 0 . 0001), length of hospital stay longer (median, 6 vs 4), and ICU admission (28% vs 9%) and case-fatality rates (21% vs 4%) higher in patients with bacterial pneumonia compared with those without bacterial pneumonia . The most common pathogen was Pseudomonas aeruginosa (32 admissions), followed by Streptococcus pneumoniae (22 admissions), Staphylococcus aureus (16 admissions), and Haemophilus influenzae (11 admissions) . Thirty-three (30%) of the pneumonias were bacteremic . Bacteremia was more common in pneumococcal than in pseudomonal pneumonia (95% vs 9%, p < 0.0001) . Compared with patients with pneumococcal pneumonia, patients with pseudomonal pneumonia had lower leukocyte and CD4+ lymphocyte counts, longer hospital stay, and similar case-fatality rate . CONCLUSIONS: P aeruginosa is becoming a common cause of both community-acquired and nosocomial bacterial pneumonia in hospitalized patients with HIV, especially in those with low leukocyte and CD4+ lymphocyte counts. Diagn Microbiol Infect Dis, 2000 Apr, 36(4), 255 - 9 Fluoroquinolone-resistant Haemophilus influenzae: frequency of occurrence and analysis of confirmed strains in the SENTRY antimicrobial surveillance program (North and Latin America); Biedenbach DJ et al.; The incidence of fluoroquinolone-resistant (FQR) Haemophilus influenzae and Moraxella catarrhalis isolated from clinical specimens remains very rare, and the identification of such strains has been previously limited to case reports from diverse geographic locations . During the 1997 through 1998 SENTRY Antimicrobial Surveillance Program, four FQR-H . influenzae (0.13% of all strains) and one FQR-M . catarrhalis strains were identified and confirmed as having elevated MICs to > or =5 FQ class drugs . Among H . influenzae strains, MICs to marketed FQs were |