Clin Infect Dis, 2001 Jan, 32(1), 2 - 8 Epub 2000 Dec 12. Antibodies to Haemophilus influenzae serotype b in the Netherlands a few years after the introduction of routine vaccination; van Den Hof S et al.; We assessed antibodies to the capsular polysaccharide of Haemophilus influenzae type b (HibPS) in the Dutch population a few years after a mass vaccination against H . influenzae (Hib) was begun . We observed sharp declines in the geometric mean titer (GMT) and the prevalence of HibPS antibodies at levels of < or =0.15 microg/mL in children who had received 4 doses of vaccine: from 8.65 microg/mL (prevalence, 99.4%) after 0-2 months to 0.8 microg/mL (prevalence, 83.3%) after 27-29 months . In adult groups, both the prevalence of HibPS antibodies and the GMT declined significantly with increasing age but remained high (prevalence, > or =83.7%; GMT, 0.73 > or = microg/mL) . We conclude that the overall immunity in the Dutch population seems satisfactory . We draw our conclusions from the current serosurveillance study and from the sharp decline in invasive Hib disease noted after the introduction of vaccination . The key questions for the future are (1) whether Hib and cross-reacting organisms will circulate sufficiently to provide natural reexposure, and (2) how long memory immunity will persist after vaccination without reexposure. Drug Metabol Drug Interact, 2000, 16(3), 217 - 28 beta-Lactamase activities and resistance to antibiotics of Haemophilus influenzae, H . parainfluenzae and H . aphrophilus strains identified in throat cultures from children; Uraz G et al.; Haemophilus bacteria are normally present in the upper respiratory tract of healthy individuals . However, these bacteria could be opportunistic pathogens especially in children . The present study was conducted to determine beta-lactamase activity of Haemophilus from the throat cultures of children with upper respiratory tract infections . 154 Haemophilus strains were isolated from throat swabs of 208 children whom had upper respiratory tract infections . Among the 154 Haemophilus strains isolated, 117 H . influenzae (76%), 35 H . parainfluenzae (22.7%), and two H . aphrophilus (13%) were identified by API NH . beta-Lactamase activity was positive in 42 isolates of 117 H . influenzae isolates, while it was negative in 75 isolates . beta-Lactamase activity was positive in 20 H . parainfluenzae isolates, and negative in 15 . All the H . aphrophilus isolates were beta-lactamase negative . It is known that beta-lactamase positive Haemophilus bacteria are resistant to some antibiotics . Therefore, the antibiotic resistance of Haemophilus was further investigated in relation to beta-lactamase activity . The in vitro antibacterial susceptibilities of Haemophilus strains for ampicillin, sulbactam-ampicillin, trimethoprim-sulfamethoxazole, gentamicin, chloramphenicol and ciprofloxacin were tested by disk diffusion method on chocolate agar . In 42 beta-lactamase-positive H . influenzae isolates, 32 isolates were resistant against ampicillin . In 20 beta-lactamase-positive H . parainfluenzae isolates, 16 were resistant against ampicillin . The two beta-lactamase negative H . aphrophilus were sensitive to ampicillin . Biotypes and serotypes were also investigated . Biotypes of H . influenzae strains were as follows: 40 strains biotype II, 25 strains biotype I, 14 strains biotype III, and 38 strains biotypes VII, VIII, V, and IV . Biotypes of 35 H . parainfluenzae strains were: 6 strains biotype III, 5 strains biotype I, 5 strains biotype IV . Biotypes of remaining 19 isolates were II, VIII, VI and VII . The serotypes of H . influenzae strains were determined by specific antiserums . Serotypes of 117 H . influenzae found were type a, b, c, d, and f. Manag Care, 2000 Sep, 9(9), 49 - 52, 54, 56-7 passim Pneumococcal conjugate vaccine for young children; Selman S et al.; Pneumococcal disease is a common cause of morbidity and mortality in the pediatric population . Pneumococcal infections, which account for most serious bacterial disease in infancy and early childhood, are a major cause of acute otitis media, sinusitis, pneumonia, bacterial meningitis, and bacteremia . Streptococcus pneumoniae is the causative agent in a large percentage of these infections, although other microorganisms also play a role . The recent emergence of drug-resistant strains has provided a strong incentive for preventing pneumococcal infections by vaccination . However, the capsular polysaccharide pneumococcal vaccines used to immunize adults are neither immunogenic nor protective in young children due to poor antibody responses . Therefore, research has focused on development of additional immunogenic pneumococcal vaccines to provide long-term immunity in children < 2 years of age . The most promising approach has been the development of a protein-polysaccharide conjugate vaccine for the seven serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) that most commonly cause infections in childhood . An effective conjugate vaccine that protects against these serotypes has the potential to prevent 85 percent of bacteremia episodes, 83 percent of meningitis episodes, and 65 percent of otitis media cases in the U.S . among children younger than 6 years . The Food and Drug Administration (FDA) recently approved the first protein-polysaccharide conjugate vaccine to prevent invasive pneumococcal diseases in infants and toddlers < 2 years of age . This conjugated vaccine against pneumococcus uses the same technology as the successful vaccine against Haemophilus influenzae type b . It consists of an immunogenic but inert protein coupled covalently to the polysaccharide coat of the selected strains of pneumococci . The conjugated antigen induces a more powerful, T-cell-based immune response in infants, which is developed by the time they are 2 months of age . Some important questions regarding this vaccine for children < 2 years of age: Is the vaccine safe? Is it immunogenic? Is it efficacious in preventing invasive pneumococcal disease and controlling otitis media? FINDINGS: Results of three randomized double-blind trials designed to evaluate the safety and immunogenicity of this vaccine in healthy children < 2 years of age were reported within the last three years . The studies found that the vaccine is safe and highly immunogenic for all seven serotypes . The most recent study, involving over 37,000 young children, also evaluated the vaccine's efficacy, and reported that the vaccine is highly effective in preventing invasive disease and has had an impact on otitis media . CONCLUSIONS: The heptavalent pneumococcal conjugate vaccine is safe and highly effective in preventing pneumococcal meningitis and bacteremic pneumonia in young children < 2 years of age; it is less effective in preventing otitis media . Based on the results of three well-designed studies demonstrating the vaccine's safety, immunogenicity, and efficacy, the vaccine is safe and effective for active immunization of children < 2 years of age against invasive disease caused by seven Streptococcus pneumoniae serotypes included in the vaccine . At this time, there is no clear medical consensus regarding its safety and efficacy for control of otitis media in children < 2 years of age . This application has not been evaluated by the FDA . The pneumococcal conjugate vaccine should be considered experimental, and has not been shown to be safe or efficacious for Streptococcus pneumoniae disease other than that caused by the serotypes included in the vaccine and for invasive infection, such as bacteremia or meningitis, caused by other microorganisms. Vaccine, 2000 Nov 22, 19(7-8), 902 - 7 Immunogenicity of a hexavalent combination vaccine in rhesus monkeys; Caulfield MJ et al.; Preclinical immunogenicity studies were conducted in rhesus monkeys to determine whether there is immune interference in the response to one or more components of a hexavalent vaccine (Hexavac) that contains antigens from Haemophilus influenzae (Hib), hepatitis B (HB), diphtheria (D), tetanus (T), acellular pertussis (aP) and inactivated polio virus (IPV) . Antibody responses were measured following co-administration of the components at three separate anatomical sites or administration as a hexavalent combination in a single site . After three injections of the hexavalent vaccine, the peak antibody responses to each component of the vaccine were >100-fold above pre-immune titers and persisted at levels >10-fold above pre-immune titers at approximately 1 year . Immune interference was observed in the peak response to HB, D and pertussis toxin, but was not seen at later time points . The results indicate that the rhesus monkey model may be useful for pre-clinical evaluation of combination vaccines. Chest, 2000 Dec, 118(6), 1591 - 7 Genotype analysis and phenotypic manifestations of children with intermediate sweat chloride test results; Desmarquest P et al.; STUDY OBJECTIVES: Cystic fibrosis (CF) is one of the most common inherited diseases among whites . Since the cloning of the CF transmembrane conductance regulator (CFTR) gene, a number of studies have focused on associations between the genotype and phenotype in CF . This had led to the progressive identification of new groups of patients, including those who have mild lung disease and those who have normal sweat chloride values (< 60 mEq/L) . The aim of the present work was to provide information on the genotype and the phenotypic characteristics of children with intermediate-range sweat chloride test results . PATIENTS AND RESULTS: We focused on children referred to the pulmonary department for various types of pulmonary disease and who had several sweat chloride test results with median values in the range of 40 to 60 mEq/L . Twenty-four patients over a 10-year period were enrolled (mean age, 4.8 years) . Respiratory manifestations at initial evaluation included recurrent bronchitis, wheezing, chronic cough, and pneumonia . The duration of the follow-up ranged from 0.5 to 10.5 years . Sputum cultures revealed the presence of Haemophilus influenzae (10 children), Staphylococcus aureus (4 children), and Pseudomonas aeruginosa (3 children) . Pancreatic insufficiency was found in two patients . Analysis of the entire coding sequence allowed identification of 16 known mutations in CFTR gene . Fifteen chromosomes (31.2%) carried a mutation in CFTR gene and one allele carried two mutations . Three patients were homozygous or double heterozygous (DeltaF508/DeltaF508, DeltaF508/3849 + 10 kb C-->T, S1235R/G551D) . The 5-thymidine allele was identified in four children . CONCLUSION: These results indicate an higher frequency of CFTR gene mutations in patients with borderline sweat chloride test results, compared to data reported in the general population . They lead to the recommendations for complete pulmonary and GI investigations in this group of patients, as well as assiduous care and medical follow-up. Chest, 2000 Dec, 118(6), 1557 - 65 Airway inflammation and etiology of acute exacerbations of chronic bronchitis; Sethi S et al.; STUDY OBJECTIVES: The etiologic role of bacterial pathogens isolated from sputum culture in 40 to 50% of acute exacerbations of chronic bronchitis (AECB) is controversial . If bacterial pathogens cause these AECB, they should be associated with greater neutrophilic airway inflammation than pathogen-negative exacerbations . DESIGN: This hypothesis was tested by comparing levels of interleukin (IL)-8, tumor necrosis factor (TNF)-alpha, and neutrophil elastase (NE) in 81 sputum samples obtained from 45 patients with AECB . Four groups were compared . In the first three groups, nontypable Haemophilus influenzae (n = 20), Haemophilus parainfluenzae (n = 27), and Moraxella catarrhalis (n = 14) were isolated as sole pathogens, respectively . In the fourth group, only normal flora was isolated (n = 20) . Paired samples, obtained from individual patients at different times, that differed in their culture results were also compared . SETTING: An outpatient research clinic at a Veterans Affairs Medical Center . PATIENTS: These patients were participating in a prospective, longitudinal study of the dynamics of bacterial infection in chronic bronchitis, for which they were seen in the study clinic on a monthly basis as well as when they were experiencing symptoms suggestive of AECB . INTERVENTIONS: None . Measurements and results: H influenzae exacerbations were associated with significantly higher sputum IL-8, TNF-alpha, and NE . M catarrhalis exacerbations demonstrated significantly higher sputum TNF-alpha and NE when compared to pathogen-negative exacerbations . H parainfluenzae-associated exacerbations had an inflammatory profile similar to pathogen-negative exacerbations . Sputum elastase level distinguished bacterial from nonbacterial AECB and correlated with clinical severity of the AECB . CONCLUSIONS: Increased airway inflammation associated with isolation of H influenzae and M catarrhalis supports an etiologic role of these pathogens in AECB. J Biol Chem, 2001 Mar 16, 276(11), 8190 - 6 Epub 2000 Dec 11. Structure of a sialic acid-activating synthetase, CMP-acylneuraminate synthetase in the presence and absence of CDP; Mosimann SC et al.; The x-ray crystallographic structure of selenomethionyl cytosine-5'-monophosphate-acylneuraminate synthetase (CMP-NeuAc synthetase) from Neisseria meningitidis has been determined at 2.0-A resolution using multiple-wavelength anomalous dispersion phasing, and a second structure, in the presence of the substrate analogue CDP, has been determined at 2.2-A resolution by molecular replacement . This work identifies the active site residues for this class of enzyme for the first time . The detailed interactions between the enzyme and CDP within the mononucleotide-binding pocket are directly observed, and the acylneuraminate-binding pocket has also been identified . A model of acylneuraminate bound to CMP-NeuAc synthetase has been constructed and provides a structural basis for understanding the mechanism of production of "activated" sialic acids . Sialic acids are key saccharide components on the surface of mammalian cells and can be virulence factors in a variety of bacterial species (e.g . Neisseria, Haemophilus, group B streptococci, etc.) . As such, the identification of the bacterial CMP-NeuAc synthetase active site can serve as a starting point for rational drug design strategies. Biochemistry (Mosc), 2000 Nov, 65(11), 1321 - 6 Analysis of HI0220 protein from Haemophilus influenzae, a novel structural and functional analog of ArcB protein from Escherichia coli; Manukhov IV et al.; A Haemophilus influenzae gene encoding a protein with high homology to ArcB receptor protein from Escherichia coli has been cloned . An error in the previously reported sequence of this gene has been found, thus increasing its open reading frame . The cloned gene comprising the entire open reading frame restores oxygen-dependent regulation of succinate dehydrogenase in an ArcB-deficient E . coli strain . Thus, this gene is a functional analog of ArcB from E . coli . By screening partially sequenced bacterial genomes using the BLAST program, proteins with high homology to ArcB protein from E . coli were found in Salmonella typhi, Yersinia pestis, Vibrio cholerae, and Pasteurella multocida . Comparison of these proteins with ArcB protein from E . coli and H . influenzae revealed conserved amino acid regions . Transmembrane helix II was shown to be highly homologous in all the ArcB-type proteins . The involvement of this region in ArcB-mediated oxygen-dependent regulation is suggested. Clin Infect Dis, 2001 Jan, 32(1), 64 - 75 Epub 2000 Dec 11. Burden of meningitis and other severe bacterial infections of children in africa: implications for prevention; Peltola H; Apart from meningococcal disease in the sub-Saharan meningitis belt, the incidence and impact of life-threatening bacterial diseases in children across Africa have not been quantified . The clinical and epidemiological data on pneumococcal, Haemophilus influenzae type b (Hib), and other forms of bacterial meningitis, as well as data on other severe bacterial infections throughout the continent were scrutinized . Pneumococci were the leading causative agents of nonepidemic meningitis and other bacteremic diseases, followed by Hib . Meningococcal diseases were less common . Mortality rates associated with pneumococcal, Hib, and meningococcal meningitis were 549 (45%) of 1211 patients, 389 (29%) of 1352 patients, and 104 (8%) of 1236 patients, respectively; sequelae occurred in 50%, 40%, and 10% of cases . At 0-4 years of age, the estimated incidences of Hib meningitis and all classic Hib diseases were 70 and 100 cases per 100,000 population per year, accounting for approximately 90,000 and 120,000 cases per year, respectively . Including older age groups and, especially, nonbacteremic Hib pneumonia in the estimates of Hib disease in Africa increased the overall numbers manifold; the numbers of pneumococcal infections were even greater . The only realistic way to combat these severe infections efficaciously would be through widespread vaccination, starting with Hib conjugates. Enferm Infecc Microbiol Clin, 2000 Aug-Sep, 18(7), 325 - 8 {Haemophilus influenzae infections in children less than 5 years of age in the community of Murcia during the 1992-1999 period}; Simarro E et al.; BACKGROUND: Invasive disease due to Haemophilus influenzae has changed substantially since the introduction of the conjugated vaccine . This report studies the incidence and the clinical-epidemiological characteristics of invasive H . influenzae disease in children under five years of age during 1992-94 (before vaccination), 1995-97 (voluntary vaccination) and 1998-99 (obligatory vaccination) . PATIENTS AND METHODS: The study was performed by reviewing the clinical histories of 39 patients with H . influenzae isolates from sterile samples, according to microbiology data . The reference population's subgroup of the study, 40,322 children under 5, comprises 60% of the total in our community . RESULTS: The overall incidence of invasive H . influenzae disease was 12.1/100,000 children under 5 and 15.7, 12.4 and 6.2 for the following periods respectively: before vaccination, during voluntary vaccination, and obligatory vaccination . All cases except one of them, were produced by H . influenzae type b and they were seen in children under 3 . Meningitis accounted for more than half of the cases (51.3%) . Fever was the most frequent sign (38 of 39 cases) . Epiglottitis was the cause of the highest average hospital stay (20.8 days) . All the patients were treated with cefotaxime, but half were also administered other antibiotics . Sequelae were seen in 7 cases, with no deaths . CONCLUSIONS: The incidence of invasive H . influenzae disease was drastically reduced and no cases were seen in the last year . However, one vaccinated patient suffered a bacteremic etmoiditis . This case and the possibility of infection due to non-b serotypes requires ongoing surveillance for these infections. Int Microbiol, 1998 Dec, 1(4), 279 - 84 Evolution of bacterial resistance to antibiotics during the last three decades; Gomez-Lus R; Bacterial resistance to antibiotics is often plasmid-mediated and the associated genes encoded by transposable elements . These elements play a central role in evolution by providing mechanisms for the generation of diversity and, in conjunction with DNA transfer systems, for the dissemination of resistances to other bacteria . At the University Hospital of Zaragoza, extensive efforts have been made to define both the dissemination and evolution of antibiotic resistance by studying the transferable R plasmids and transposable elements . Here we describe the research on bacterial resistance to antibiotics in which many authors listed in the references have participated . The aspects of bacterial resistance dealt with are: (i) transferable resistance mediated by R plasmids in Gram-negative bacteria, (ii) R plasmid-mediated resistance to apramycin and hygromycin in clinical strains, (iii) the transposon Tn1696 and the integron In4, (iv) expression of Escherichia coli resistance genes in Haemophilus influenzae, (v) aminoglycoside-modifying-enzymes in the genus Mycobacterium with no relation to resistance, and (vi) macrolide-resistance and new mechanisms developed by Gram-positive bacteria. J Vet Diagn Invest, 2000 Nov, 12(6), 541 - 6 In vitro susceptibility of porcine respiratory pathogens to tilmicosin; DeRosa DC et al.; Bacterial isolates obtained from swine with various clinical diseases were tested for susceptibility to tilmicosin by minimum inhibitory concentration (MIC) and Kirby-Bauer disk diffusion tests using National Committee on Clinical Laboratory Standards methodology . The tilmicosin MIC90 was < or =0.125 microg/ml for Erysiopelothrix rhusiopathiae, < or = 1 microg/ml for Haemophilus parasuis isolates, 8 microg/ml for Actinobacillus suis and Pasteurella multocida type A, 16 microg/ml for toxigenic and nontoxigenic P . multocida type D, 64 microg/ml for Bordetella bronchiseptica, and >128 microg/ml for Staphylococcus hyicus and Streptococcus suis . The results of disk diffusion testing matched well with the MIC results for each pathogen . This in vitro survey of tilmicosin activity against various swine isolates suggests that further clinical evaluation of tilmicosin in swine may be warranted for disease associated with E . rhusiopathiae, H . parasuis, and A . suis but not B . bronchiseptica, S . suis, or S . hyicus. Acta Paediatr, 2000 Nov, 89(11), 1316 - 21 A single intramuscular dose of ceftriaxone changes nasopharyngeal bacterial flora in children with acute otitis media; Heikkinen T et al.; The increasing prevalence of drug-resistant bacteria is attributed to the extensive use of antibiotics, which causes selective pressure on the nasopharyngeal bacterial flora . Shortened courses of antibiotics have been proposed to decrease the development of resistant strains . We determined the effect of a single intramuscular dose of ceftriaxone (50 mg/kg) on the nasopharyngeal bacterial flora in 167 children (median age 13 mo) with acute otitis media . Nasopharyngeal samples for bacterial culture were obtained before and 5 d after treatment with ceftriaxone . Before treatment, Moraxella catarrhalis was isolated in 99 (59%) children, Streptococcus pneumoniae in 87 (52%), and Haemophilus influenzae in 53 (32%) . After treatment, M . catarrhalis was found in 62 (37%) children, which constitutes a 37% decrease in the colonization rate by this pathogen (p < 0.001) . S . pneumoniae was isolated in 50 (30%; 43% decrease) and H . influenzae in 17 (10%; 68% decrease) children after treatment (p < 0.001 for both) . Before treatment, 60% of pneumococcal isolates were sensitive to penicillin, 26% were of intermediate susceptibility, and 14% were penicillin-resistant . Eradication of S . pneumoniae occurred mainly in children with penicillin-sensitive isolates . As a consequence, only 24% of pneumococcal isolates that remained after treatment were sensitive to penicillin, 59% were penicillin-intermediate, and 16% were penicillin-resistant . A single dose of ceftriaxone resulted in significant changes in the nasopharyngeal bacterial flora, increasing the relative prevalence of pneumococcal strains with decreased susceptibility to penicillin. J Antimicrob Chemother, 2000 Dec, 46(6), 921 - 9 The effect of three broad-spectrum antimicrobials on mononuclear cell responses to encapsulated bacteria: evidence for down-regulation of cytokine mRNA transcription by trovafloxacin; Purswani M et al.; The effect of trovafloxacin, ciprofloxacin and ceftriaxone on cytokine production of human peripheral blood mononuclear cells (PBMCs) was examined . PBMC responses were measured after stimulation with lipopolysaccharide (LPS), lipoteichoic acid (LTA) or killed or viable Streptococcus pneumoniae and Haemophilus influenzae . Trovafloxacin inhibited the production of tumour necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6 and IL-8 by PBMCs after stimulation with either LPS or LTA by 83% . Similar inhibition occurred in PBMCs incubated with killed or live bacteria and trovafloxacin, but not with ciprofloxacin or ceftriaxone . The relevance of this in vitro observation was explored by examining TNF-alpha and IL-6 responses in trovafloxacin-treated mice . Serum concentrations of both cytokines 1 h after LPS challenge were 95% less than serum concentrations in mice that were not given trovafloxacin . Reverse transcription- polymerase chain reaction studies of the mechanisms determining cytokine down-regulation demonstrated that trovafloxacin reduced TNF-alpha, IL-1beta and IL-6 mRNA to levels similar to those of unstimulated cells . These observations indicate that trovafloxacin can consistently and significantly reduce production of cytokines that play an important role in sepsis . In vitro, this effect can occur in the presence of bacteriolysis and is associated with inhibition of transcription of cytokine genes. FEMS Microbiol Ecol, 2000 Dec 1, 34(2), 91 - 102 A bioluminescent derivative of Pseudomonas putida KT2440 for deliberate release into the environment; Ramos C et al.; Recombinant derivatives of Pseudomonas putida strain KT2440 are of potential interest as microbial inoculants to be deliberately released for agricultural applications . To facilitate tracking of this strain and its derivatives after introduction into the environment, a mini-Tn5-'luxAB transposon was introduced into the chromosome of P . putida KT2440, yielding strain P . putida S1B1 . Sequencing of the DNA region located upstream of the 'luxAB genes and similarity search with the P . putida KT2440 genome sequence, localized the transposon within a 3021-bp open reading frame (ORF), whose translated sequence showed significant similarity with the hypothetical YdiJ proteins from Escherichia coli and Haemophilus influenzae . A second ORF adjacent to and divergent from the ydiJ sequence was also found and showed significant homology with various LysR-type transcriptional activator proteins from several bacteria . Disruption of the ydiJ locus in P . putida S1B1 did not affect the survival of the strain in unvegetated or vegetated soils . Bioluminescent detection of P . putida S1B1 cells enriched in selective media directly from soil allowed detection of culturable cells in soil samples over a period of at least 8 months . The addition of the luxAB biomarker facilitates tracking in the root system of several plant species grown under sterile and non-sterile conditions . The correlation of the bioluminescent phenotype with the growth activity of P . putida S1B1 cells colonizing the root system of barley and corn plants was estimated by monitoring ribosomal contents using quantitative hybridization with fluorescence-labeled ribosomal RNA probes . A correlation between inoculum density, light output, and ribosomal contents was found for P . putida cells colonizing the root system of barley seedlings grown under sterile conditions . Although ribosomal contents, and therefore growth activity, of P . putida S1B1 cells extracted from the rhizosphere of corn plants grown in non-sterile soil were similar to those found in starved cells, the luminescent system permitted non-destructive in situ detection of the strain in the upper root system. Nat Struct Biol, 2000 Dec, 7(12), 1172 - 7 Crystal structure of the bacterial protein export chaperone secB; Xu Z et al.; SecB is a bacterial molecular chaperone involved in mediating translocation of newly synthesized polypeptides across the cytoplasmic membrane of bacteria . The crystal structure of SecB from Haemophilus influenzae shows that the molecule is a tetramer organized as a dimer of dimers . Two long channels run along the side of the molecule . These are bounded by flexible loops and lined with conserved hydrophobic amino acids, which define a suitable environment for binding non-native polypeptides . The structure also reveals an acidic region on the top surface of the molecule, several residues of which have been implicated in binding to SecA, its downstream target. J Clin Microbiol, 2000 Dec, 38(12), 4649 - 52 Characterization of non-type B Haemophilus influenzae strains isolated from patients with invasive disease . The HI Study Group; Cerquetti M et al.; Forty-one non-type b Haemophilus influenzae isolates from cases of invasive disease were characterized . By PCR capsular genotyping, 33 nonencapsulated strains, 4 type f isolates, and 4 b(-) strains were identified . By pulsed-field gel electrophoresis, the nonencapsulated isolates exhibited great genetic heterogenicity, whereas the type f and the b(-) strains seemed to have a clonal spread . Occurrence of the hifA gene was found by PCR in 18% of the nonencapsulated, 50% of the b(-), and all of the type f strains . Hemagglutinating fimbriae were generally expressed by nonencapsulated isolates when fimbrial gene hifA was present . Two nonencapsulated isolates not susceptible to ampicillin were detected; no strains were positive for beta-lactamase production. J Clin Microbiol, 2000 Dec, 38(12), 4412 - 9 Antigenic diversity of Haemophilus somnus lipooligosaccharide: phase-variable accessibility of the phosphorylcholine epitope; Howard MD et al.; The lipooligosaccharide (LOS) of Haemophilus somnus undergoes antigenic phase variation, which may facilitate evasion from the bovine host immune response and/or colonization and dissemination . However, LOS antigenic diversity in H . somnus has not been adequately investigated . In this study, monoclonal antibodies (MAbs) specific to various LOS epitopes were used to investigate antigenic variation and stability in LOS from H . somnus strains and phase variants . Clinical isolates of H . somnus exhibited intrastrain, as well as interstrain, antigenic heterogeneity in LOS when probed with MAbs to outer core oligosaccharide epitopes in an enzyme-linked immunosorbent assay (ELISA) . However, epitopes reactive with MAbs directed predominately to the inner core heptose region were highly conserved . At least one epitope, which was expressed in few strains, was identified . One LOS component affected by phase variation was identified as phosphorylcholine (PCho), which is linked to the primary glucose residue . Inhibition ELISA, immunoblotting, and electrospray-mass spectrometry were used to confirm that MAb 5F5.9 recognized PCho . LOS reactivity with MAb 5F5.9 was associated with loss of most of the outer core oligosaccharide, indicating that reactivity with PCho was affected by phase variation of the glucose residues in this region . Our results indicate that outer core epitopes of H . somnus LOS exhibit a high degree of random, phase-variable antigenic heterogeneity and that such heterogeneity must be considered in the design of vaccines and diagnostic tests. Bone Marrow Transplant, 2000 Nov, 26(9), 1017 - 9 Recurrent penicillin-resistant pneumococcal sepsis after matched unrelated donor (MUD) transplantation for refractory T cell lymphoma; Tauro S et al.; Patients who undergo splenectomy and recipients of allogeneic marrow (alloBMT) or peripheral stem cell transplantation are at increased risk of overwhelming infection from encapsulated organisms such as Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis . As prophylaxis against these pathogens splenectomised patients are immunised and may also receive antibiotics for life . We report relapsing overwhelming sepsis caused by penicillin-resistant pneumococcus in a patient who was immunised and received prophylactic phenoxymethylpenicillin for 8 months following splenectomy and matched unrelated donor (MUD) marrow transplantation for refractory T cell lymphoma . No obvious focus of sepsis was found during any of the three episodes and S . pneumoniae serogroup 6, subtype 6B was isolated from blood cultures on each occasion . He was treated with i.v . cephalosporins, as the organisms were resistant to penicillin with a minimum inhibitory concentration (MIC) of 2.0, and there was complete resolution of symptoms each time . In the light of recurrent sepsis with this penicillin-resistant organism the decision was made to give prophylactic levofloxacin for the next 12 months . This case illustrates that the choice of prophylactic regimen and the treatment of sepsis in immunocompromised patients remain difficult and challenging issues. Braz J Infect Dis, 1998 Feb, 2(1), 25 - 30 Evaluation of the in vitro Activity of Cefprozil Relative to Other Oral Antimicrobial Agents Against Bacteria in Clinical Specimens from Patients in São Paulo With Respiratory Tract Infections; Sader HS et al.; Cefprozil is a new oral second generation cephalosporin . Its in vitro antimicrobial activity was evaluated against 371 recent clinical isolates from patients with respiratory infections . We tested the susceptibility of 244 streptococci (96 Streptococcus pneumoniae, 105 group viridans streptococci, 32 Streptococcus agalactiae, and 11 group A beta-hemolitic streptococci) 107 Haemophilus influenzae, and 20 oxacillin-susceptible S.aureus (OSSA) . The isolates were susceptibility tested against cefprozil, cefaclor and amoxicillin/clavulanic acid by the E-test method; and against cefadroxil, cefuroxime, cefetamet, erythromycin, and azythromycin by disk diffusion . The methods and the susceptibility categorization followed the National Committee for Clinical Laboratory Standards (NCCLS) procedures . Amoxicillin/clavulanic acid was slightly more active againstH.influenzae (MICs(90) 0.5microg/mL) than cefprozil or cefaclor (MICs(90) 4 and 2microg/mL respectively) . Cefprozil demonstrated potent activity against streptococci . Against S.pneumoniae, cefprozil was 2-4 fold more active than cefaclor (MICs(90)0.125 and 0.38microg/mL, respectively) . S . pneumoniae susceptibility was 84% to penicillin, 95% to erythromycin and 97% to azithromycin by disk diffusion . Viridans streptococci showed higher MICs for cefprozil and cefaclor (MICs(90) 4microg/mL and 8microg/mL, respectively) and only 50% susceptibility to the macrolides . Cefprozil was four times more active than cefaclor and as active as amoxieillin/clavulanic acid against group A beta-hemolytic streptococci and S.agalactiae . These three compounds showed similar activity against OSSA . In conclusion, cefprozil demonstrated excellent in vitro activity against bacterial species responsible for respiratory infections in Sao Paulo. Pediatr Infect Dis J, 2000 Nov, 19(11), 1045 - 52 Immunization against hepatitis A in the first year of life: priming despite the presence of maternal antibody; Dagan R et al.; BACKGROUND: Maternal antibodies interfere with hepatitis A vaccination in young infants . We examined the response to a high dose hepatitis A vaccine administered concomitantly with a combination of diphtheria-tetanus toxoids-acellular pertussis-inactivated poliovirus vaccine/Haemophilus influenzae type b vaccine to initially seropositive vs . initially seronegative infants . METHODS: Three hundred subjects were originally planned to be enrolled at age 6 to 10 weeks and received hepatitis A vaccine (formalin-inactivated vaccine, SB-Bio, 720 enzyme-linked immunosorbent assay units) at 2, 4 and 6 months concomitantly with a diphtheria-tetanus toxoids-acellular pertussis-inactivated poliovirus vaccine/H . influenzae type b vaccine . Children initially seropositive received a booster dose at 12 months of age . An additional 100 twelve-month-old infants previously not vaccinated with hepatitis A vaccine were given 1 dose, to observe the primary response at that age . Reactogenicity was recorded on diary cards for the 3 subsequent days . Immunogenicity was measured at Months 2, 4, 5, 10 and 11 after administration of the first vaccine dose . For the subjects enrolled at 12 months, blood was drawn before and 1 month after the first vaccination . RESULTS: Of 297 initially enrolled infants 36% were seronegative before vaccination (Group A) . The geometric mean concentration (GMC) (milli-International Units/ml) of the seropositive infants (Group B) before immunization was 2587 . The GMCs of Group A infants 1 month after each dose and at 12 months of age were 93, 518, 1656 and 786, respectively . For Group B infants, the respective GMCs were 1165, 460, 508 and 167 . One hundred subjects of Group B received a booster dose at age 12 months; at Month 13 all were seropositive with a GMC of 1902 . For comparison, a third group of 100 not previously immunized 12-month-old infants (Group C) were enrolled and received 1 dose of hepatitis A vaccine with pre- and postimmunization GMCs of 52 and 120, respectively . CONCLUSIONS: Our results suggest that the initially seropositive infants were primed despite maternal antibody interference . The hepatitis A vaccine was well-tolerated in this population of young infants. Pediatr Infect Dis J, 2000 Nov, 19(11), 1040 - 5 Bacteriologic and clinical efficacy of one day vs . three day intramuscular ceftriaxone for treatment of nonresponsive acute otitis media in children; Leibovitz E et al.; BACKGROUND: One dose of intramuscular ceftriaxone has been recently licensed in the United States for the treatment of acute otitis media . However, data regarding the bacteriologic and clinical efficacy of this regimen in the treatment of nonresponsive acute otitis media are incomplete . OBJECTIVES: To determine the bacteriologic and clinical efficacy of a 1-day 50-mg/kg vs . a 3-day 50-mg/kg/day intramuscular ceftriaxone regimen in the treatment of nonresponsive acute otitis media in children . PATIENTS AND METHODS: In an open, prospective study 109 patients ages 3 to 36 months with culture-proved, nonresponsive acute otitis media were randomized to receive 1 (n = 49) or 3 (n = 60) 50-mg/kg/day intramuscular ceftriaxone doses, respectively . Middle ear fluid was aspirated for culture by tympanocentesis on the day of enrollment (Day 1); a second tympanocentesis with middle ear fluid culture was performed on Days 4 to 5 . Additional middle ear fluid cultures were obtained if clinical relapse occurred after completion of therapy . Bacteriologic failure was defined by positive cultures on Days 4 to 5 . Patients were followed until Day 28 after completion of therapy . Susceptibility of the middle ear pathogens was measured by E-test . RESULTS: Organisms recovered (n = 133) were Streptococcus pneumoniae (30 and 35 isolates for the 1-day and 3-day treatment group, respectively), Haemophilus influenzae (26 and 38, respectively) and Moraxella catarrhalis (n = 4) . Of the 30 S . pneumoniae isolated from the 1-day group, 27 (90%) and 6 (20%) were nonsusceptible to penicillin and ceftriaxone, respectively; 9 of 27 (33%) were fully resistant to penicillin . Thirty-four (97%) and 6 (17%) of the 35 S . pneumoniae isolated from the 3-day group were nonsusceptible to penicillin and ceftriaxone, respectively; 16 of 34 (47%) were fully resistant to penicillin . Bacterial eradication of all H . influenzae and penicillin-susceptible S . pneumoniae was achieved in both treatment groups . Bacterial eradication of 14 of 27 (52%) and 33 of 34 (97%) penicillin-nonsusceptible S . pneumoniae was achieved in the 1-day and 3-day group, respectively . Seven (50%) of the 14 patients from the 2 groups who did not achieve bacterial eradication did not improve clinically on Days 4 to 5 and required additional ceftriaxone treatment . CONCLUSION: The 3-day intramuscular ceftriaxone regimen was significantly superior to the 1-day intramuscular ceftriaxone regimen in the treatment of nonresponsive acute otitis media caused by penicillin-resistant S . pneumoniae. Curr Infect Dis Rep, 2000 Aug, 2(4), 327 - 331 Changing Epidemiology of Bacterial Meningitis in the United States; Short WR et al.; Bacterial meningitis is an important cause of morbidity and mortality in the United States and throughout the world . Over the past 20 years, there have been significant changes in the epidemiology of bacterial meningitis . The most important change is the decrease in the frequency of Haemophilus influenzae type b as the most common etiologic agent of bacterial meningitis, since the H . influenzae type b conjugate vaccine was introduced . Streptococcccus pneumoniae is now the major cause of bacterial meningitis in the US and bacterial meningitis is now a disease predominantly of adults, rather than of infants and children . Emergence of antimicrobial resistance in S . pneumoniae has also altered the approach to antimicrobial therapy in patients with pneumococcal meningitis, indicating the need to use preventive strategies to reduce the frequency of this serious infection . Recent licensure of the heptavalent pneumococcal conjugate vaccine will likely decrease the overall incidence of pneumococcal meningitis. Curr Infect Dis Rep, 2000 Apr, 2(2), 121 - 129 Current and Future Use of Vaccines for Viral and Bacterial Respiratory Tract Infections; Ottolini MG; Viral and bacterial respiratory infections remain the number one cause of infectious disease-related deaths around the world . In the past, vaccines were often created by repeatedly passing laboratory cultures to develop attenuated strains or simply by inactivating live cultures of pathogens . A variety of new and innovative technologies are being applied to develop vaccines against the more elusive pathogens . A variety of protein conjugates have been used to greatly enhance the immunogenicity of Haemophilus influenzae type B vaccine, and are now being employed for new pneumococcal and meningococcal vaccines . Live attenuated vaccine strains of respiratory syncytial virus and influenza, which induce protective immunity through localized replication in the nasopharynx, may soon be available for routine use . Future innovations may include genetic vaccines that introduce DNA into host cells to produce specific protective antigens, along with a desired cytokine response to induce a protective immune response. Curr Infect Dis Rep, 2000 Feb, 2(1), 31 - 43 The Use of Molecular Techniques for the Diagnosis and Epidemiologic Study of Sexually Transmitted Infections; Black CM et al.; Molecular diagnostic tests are more sensitive and, in many cases, more specific than conventional laboratory methods for the detection of sexually transmitted infections . Here, we review recently developed molecular methods for the diagnosis and subtyping of the most common sexually transmitted infections: infections caused by Chlamydia trachomatis, Neisseria gonorrhoeae, human papillomavirus, Trichomonas vaginalis, and the agents of genital ulcer disease (Haemophilus ducreyi, herpes simplex virus, Treponema pallidum, and Calymmatobacterium granulomatis) . We also provide an overview of the laboratory diagnostic tests and clinical specimens to use when infection with these agents is suspected. Curr Infect Dis Rep, 1999 Dec, 1(5), 417 - 426 Vaccination in Travelers; Hill DR; Vaccination of populations throughout the world has led to dramatic decreases in morbidity and mortality from many infectious diseases, including poliomyelitis and measles . In the United States, for example, morbidity and mortality from invasive disease from Haemophilus influenzae type b has decreased more than 99% . International travelers should ensure that they are up-to-date on their routine immunizations and then consider vaccination against other diseases based on risk . This article reviews new vaccines such as those against rotavirus, Lyme disease, and enterotoxigenic Escherichia coli and provides updated information on the risk of typhoid fever and the efficacy of vaccination against it . The use of hepatitis A vaccine in outbreak control, the safety of yellow fever vaccine, and the importance of protecting travelers against rabies exposure are also discussed . Vaccination is an important way for travelers to maintain their health before, during, and after travel. Curr Infect Dis Rep, 1999 Jun, 1(2), 153 - 159 Acute Meningitis; Pfister HW et al.; Recent major epidemiologic trends in bacterial meningitis include a dramatic decline in the incidence of Haemophilus influenzae meningitis since the introduction of the protein-conjugated H . influenzae vaccines, and a worldwide increase in infections with antibiotic-resistant strains of bacterial pathogens . Cases of meningitis caused by resistant strains require an alternative therapeutic strategy . Animal studies have identified inflammatory mediators, eg, chemokines, excitatory amino acids, and endothelins, which are involved in the pathophysiology of bacterial meningitis . There is increasing evidence that reactive oxygen species (ROS), reactive nitrogen species, peroxynitrite, and matrix metalloproteinases contribute to brain damage during bacterial meningitis . The cytotoxic effects of ROS and peroxynitrite include the initiation of lipid peroxidation and the induction of DNA single-strand breakage . Damaged DNA activates poly(ADP-ribose) polymerase (PARP) . Recent experimental data suggest that lipid peroxidation and PARP activation play a role in the development of meningitis-associated intracranial complications and brain injury . Agents that interfere with the production of ROS and peroxynitrite, and interfere with lipid peroxidation and PARP activation, may represent novel, therapeutic strategies by which meningitis-associated brain damage can be limited, therefore improving the outcome of this serious disease. Int J Antimicrob Agents, 2000 Nov, 16(3), 281 - 5 The role of fluoroquinolones in respiratory tract infections: community acquired pneumonia; Garcia-Rodriguez JA et al.; Newer fluoroquinolones may play an important role in the management of community acquired pneumonia . They retain activity similar to older fluoroquinolones against Gram-negative bacteria and are significantly more active against Gram-positive bacteria, especially pneumococci . They are also active against bacteria causing atypical pneumonia, penicillin-sensitive and -resistant and macrolide-sensitive and -resistant pneumococci and against beta-lactamase producing and non-producing Haemophilus influenzae . They have similar or slightly lower activity than ciprofloxacin against other Gram-negative organisms . They have rapid bactericidal activity and attain good lung tissue levels . Clinical studies show results similar or better than older treatments . Their impact on ecology and resistance remains to be elucidated but data on side effects and toxicity must be carefully evaluated. Int J Antimicrob Agents, 2000 Nov, 16(3), 259 - 62 Epidemiological survey of bacterial resistance in upper respiratory tract infections in italy; Cornaglia G et al.; The vast majority of infections in the upper airways are caused by four bacterial species;, in Italy as elsewhere, antibiotics resistant strains are emerging . Enzymatic resistance to beta-lactams in Haemophilus influenzae is becoming more important and affects 15% of isolates . On the other hand less than 0.3% of H . influenzae strains are fluoroquinolone-resistant . The number of beta-lactamase-producing Moraxella catarrhalis strains in Italy has been thought to be lower than in other countries, but recent studies suggest 90% of strains are positive, a figure similar to figures reported in the international literature . The most recent data estimate high-level resistance to penicillin in pneumococci to be around 5%, but varies greatly in different geographical areas and with the different origins of the isolates . In spite of the low incidence of penicillin-resistant strains, the most recent figures for macrolide-resistance in Streptococcus pneumoniae range from 26.4 to 31.7% . More than 3 years after the dramatic increase in erythromycin-resistant Streptococcus pyogenes, the resistance levels in Italy are still among the highest in the world . Unlike the experience in other countries, resistance is often related not to the active efflux of antibiotic from the bacterial cell but to ribosomal methylation, thus affecting not only 14- and 15-membered macrolides, but also 16-membered compounds and lincosamides. Vaccine, 2000 Nov 8, 19(6), 601 - 12 Application of genomics and proteomics for identification of bacterial gene products as potential vaccine candidates; Chakravarti DN et al.; The ability of bioinformatics to characterize genomic sequences from pathogenic bacteria for prediction of genes that may encode vaccine candidates, e.g . surface localized proteins, has been evaluated . By applying appropriate tools for genomic mining to the published sequence of Haemophilus influenzae Rd genome, it was possible to identify a putative vaccine candidate, the outer membrane lipoprotein, P6 . Proteomics complements genomics by offering abilities to rapidly identify the products of predicted genes, e.g . proteins in outer membrane preparations . The ability to identify the P6 protein uniquely from entries in a sequence database from the expected peptide-mass fingerprint of P6 demonstrates the power of proteomics . The application of proteomics for identification of vaccine candidates for another pathogenic bacterium, Helicobacter pylori using two different approaches is described . The first involves rapid identification of a series of monoclonal antibody reactive proteins from N-terminal sequence tags . The other approach involves identification of proteins in outer membrane preparations by 2-D electrophoresis followed by trypsin digestion and peptide mass map analysis . Our combined studies demonstrate that utilization of genome sequences by application of bioinformatics through genomics and proteomics can expedite the vaccine discovery process by rapidly providing a set of potential candidates for further testing. Intensive Care Med, 2000 Sep, 26(9), 1369 - 72 Tracheal colonisation within 24 h of intubation in patients with head trauma: risk factor for developing early-onset ventilator-associated pneumonia; Sirvent JM et al.; OBJECTIVE: To investigate if tracheal colonisation within 24 h of intubation is a risk factor for developing early-onset ventilator-associated pneumonia (EP) in patients with head trauma . DESIGN: A prospective study in an intensive care unit of a university hospital . POPULATION: One hundred intubated patients were included with head trauma and Glasgow coma score at admission < or =12 . METHODS: We took tracheal aspirate samples within 24 h of intubation and performed a protected bronchoalveolar mini-lavage when clinical diagnosis of pneumonia was made . MEASUREMENTS AND RESULTS: On admission time 68 patients (68%) were colonised in trachea, 22 patients were colonised by Staphylococcus aureus, 20 by Haemophilus influenzae, six by Streptococcus pneumoniae and 20 by gram-negative bacilli . The incidence of EP was 26%, and the microorganisms involved were Staph . aureus (44%), H . influenzae (31%), Strep . pneumoniae (12%), and gram-negative bacilli (13%) . A multivariate logistic regression analysis showed that the tracheal colonization by Staph . aureus, H . influenzae or Strep . pneumoniae within 24 h of intubation was an independent risk factor for developing EP (odds ratio: 28.9; 95% confidence interval: 1.59-52.5) . CONCLUSION: Colonisation of the trachea within 24 h of intubation by Staphylococcus aureus, Haemophilus influenzae or Streptococcus pneumoniae is a risk factor for developing EP in patients with head trauma. Rev Esp Quimioter, 2000 Sep, 13(3), 306 - 13 {Pharmacodynamic basis for the use of amoxicillin-clavulanic acid in respiratory infections due to Streptococcus pneumoniae: In vitro studies in an experimental model}; Gomez-Lus ML et al.; Amoxicillin-clavulanic acid is a first choice treatment for respiratory tract infections caused by Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis . In a previous study we observed its high efficacy against penicillin-susceptible and intermediate-resistant strains of S . pneumoniae . We aimed to study the efficacy of this antibiotic against three strains of S . pneumoniae (susceptible, intermediate and resistant to penicillin) in a mouse model of pneumonia, and to determine the influence of the time of starting treatment and the in vitro postantibiotic effect . We also determined the serum levels of the antimicrobial agent in the mice, and correlated the pharmacodynamic parameters (Cmax/MIC, AUC/MIC and T>MIC) with the survival rate to establish the best predictor of efficacy . MICs with amoxicillin-clavulanic acid were 0 . 03 mg/l, 0.25 mg/l and 2 mg/l for the penicillin-susceptible, -intermediate and -resistant strains, respectively . The ED90 were approximately 5 mg/kg for susceptible strains, 25 mg/kg for the intermediate and 50 mg/kg for the resistant strains . We observed a lower survival rate (approximately 55%) when the treatment began 31 h after infection than when it began 5 h (100%) and 19 h (approximately 90-100%) afterwards . Serum levels were dose dependent and the correlation with the pharmacodynamic parameters showed a significant association between survival and the T>MIC (r = 0.946) . In vitro postantibiotic effects with 1, 4 and 10 times the MIC were 0.96 to 1.69 h for susceptible strains, 0.38 to 1.23 h for intermediate, and 1.52 to 2 . 20 h for resistant strains . These results show the high efficacy of this antibiotic combination against strains with variable susceptibility to penicillin, with this activity being related mainly to the T>MIC of the microorganism . The postantibiotic effect would prolong the effect of the antibiotic in the dosing interval . These parameters and antimicrobial effects are important in terms of the clinical application of this antimicrobial agent. Rev Esp Quimioter, 2000 Sep, 13(3), 291 - 6 {Comparison of the activity of different macrolides on strains of Haemophilus influenzae}; Ramirez de Arellano JA et al.; In this study we evaluated the activity of macrolides and b-lactam antimicrobials on Haemophilus influenzae isolated in 1998 in eight Spanish cities . A total of 174 clinical isolates were examined . Overall, 29% of the isolates were found to produce b-lactamase . Azithromycin was the most active of the macrolides tested in this study (MIC90 of 4 mg/l); no azithromycin-resistant strains were found . Ampicillin resistance was 29% . We found one strain intrinsically resistant to beta-lactam agents (0.65% overall); and two beta-lactamase-positive strains that were resistant to amoxicillin-clavulanic acid (1.2%) . The presence of these strains, while uncommon at present, makes it necessary to test the activity of antimicrobial drugs on H . influenzae. An Esp Pediatr, 2000 Oct, 53(4), 369 - 71 {Meningitis due to haemophilus influenzae type f}; Gonzalez Lopez M et al.; We report an immunocompetent 5-month-old boy with Haemophilus influenzae type f (Hif) meningitis . The patient had previously been immunized with two doses of Hib conjugate vaccine (PRP-T) . Vaccination failure was initially suspected based on Gram stain report . The results of culture identified a non-b Haemophilus influenzae capsular serotype (Hif).Non-Hib serotypes should be considered as potential pathogenic agents in children under the age of 5 years with invasive diseases . An adequate epidemiological surveillance system would be helpful in detecting the role of these non-b Hif serotypes as significant pathogens, which appear to be on the increase. Braz J Infect Dis, 1999 Dec, 3(6), 215 - 219 Comparative In Vitro Activities of Moxifloxacin (Bay 12-8039) and Other Antimicrobial Agents Against Respiratory Tract Pathogens in Brazil; Del' Alamo L et al.; Clinical isolates of respiratory tract pathogens were susceptibility tested against six different antimicrobial agents . The in vitro activity of moxifloxacin was compared with that of levofloxacin, cefaclor, amoxicillin-clavulanate acid, azithromycin and trimethoprim-sulfamethoxazole against 111 isolates, including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and other species isolated from respiratory tract infections . All isolates were susceptible to moxifloxacin, except for two isolates of Pseudomonas aeruginosa which showed intermediate-resistance (MIC=6microg/mL), and one isolate of Escherichia coli which showed resistance (MIC>32microg/mL) . Only moxifloxacin and amoxicillin-clavulanic acid were active against 100% of S . pneumoniae isolates at the suceptible breakpoint (MIC90, 0.25 microg/mL and 0.064 microg/mL respectively) . The rank order of the activity among this group of drugs against S . pneumoniae was as follows (% of susceptibility): moxifloxacin = amoxicillin-clavulanic acid (100%) > levofloxacin (97%) > cefaclor (71%) > trimethoprim-sulfamethoxazole (54%) > azithromycin (53%) . Except for trimethoprim-sulfamethoxazole, all antimicrobial agents were 100% active against H . influenzae and M . catarrhalis . The fluoroquinolones, moxifloxacin and levofloxacin, were the most potent compounds against these pathogens (MIC(90) 0.032 0.19 microg/mL) . These in vitro susceptibility testing data of moxifloxacin support the view that this fluoroquinolone will have an important therapeutic role in the treatment of respiratory tract diseases. Infect Immun, 2000 Dec, 68(12), 6903 - 11 Cellular internalization of cytolethal distending toxin from Haemophilus ducreyi; Cortes-Bratti X et al.; The chancroid bacterium Haemophilus ducreyi produces a toxin (HdCDT) which is a member of the recently discovered family of cytolethal distending toxins (CDTs) . These protein toxins prevent the cyclin-dependent kinase cdc2 from being activated, thus blocking the transition of cells from the G(2) phase into mitosis, with the consequent arrest of intoxicated cells in G(2) . It is not known whether these toxins act by signaling from the cell surface or intracellularly only . Here we report that HdCDT has to undergo at least internalization before being able to act . Cellular intoxication was inhibited (i) by removal of clathrin coats via K(+) depletion, (ii) by treatment with drugs that inhibit receptor clustering into coated pits, and (iii) in cells genetically manipulated to fail in clathrin-dependent endocytosis . Intoxication was also completely inhibited in cells treated with bafilomycin A1 or nocodazole and in cells incubated at 18 degrees C, i.e., under conditions known to block the fusion of early endosomes with downstream compartments . Moreover, disruption of the Golgi complex by treatment with brefeldin A or ilimaquinone blocked intoxication . In conclusion, our data indicate that HdCDT enters cells via clathrin-coated pits and has to be transported via the Golgi complex in order to intoxicate cells . This is the first member of the family of CDTs for which cellular internalization and some details of the pathway have been demonstrated. Infect Immun, 2000 Dec, 68(12), 6896 - 902 Nucleotide sequence analysis of hypervariable junctions of Haemophilus influenzae pilus gene clusters; Read TD et al.; Haemophilus influenzae pili are surface structures that promote attachment to human epithelial cells . The five genes that encode pili, hifABCDE, are found inserted in genomes either between pmbA and hpt (hif-1) or between purE and pepN (hif-2) . We determined the sequence between the ends of the pilus clusters and bordering genes in a number of H . influenzae strains . The junctions of the hif-1 cluster (limited to biogroup aegyptius isolates) are structurally simple . In contrast, hif-2 junctions are highly diverse, complex assemblies of conserved intergenic sequences (including genes hicA and hicB) with evidence of frequent recombination . Variation at hif-2 junctions seems to be tied to multiple copies of a 23-bp Haemophilus intergenic dyad sequence . The hif-1 cluster appears to have originated in biogroup aegyptius strains from invasion of the hpt-pmbA region by a DNA template containing the hif-2 genes with termini in the hairpin loop of flanking intergenic dyad sequences . The pilus gene clusters are an interesting model of a mobile "pathogenicity island" not associated with a phage, transposon, or insertion element. Chest, 2000 Nov, 118(5), 1344 - 54 Community-acquired pneumonia: etiology, epidemiology, and outcome at a teaching hospital in Argentina; Luna CM et al.; OBJECTIVE: To survey the etiology and epidemiology of community-acquired pneumonia (CAP) in relation to age, comorbidity, and severity and to investigate prognostic factors . DESIGN: Prospective epidemiologic study, single center . SETTING: University hospital at Buenos Aires, Argentina . PATIENTS: Outpatients and inpatients fulfilling clinical criteria of CAP . INTERVENTIONS: Systematic laboratory evaluation for determining the etiology, and clinical evaluation stratifying patients into mild, moderate, and severe CAP (groups 1 to 3), a clinical rule used for hospitalization . RESULTS: During a 12-month period, 343 patients (mean age, 64.4 years; range, 18 to 102 years) were evaluated . We found 167 microorganisms in 144 cases (yield, 42%) . Streptococcus pneumoniae, the most common pathogen, was isolated in 35 cases (24%) . Mycoplasma pneumoniae, present in 19 (13%), was second in frequency in group 1; Haemophilus influenzae, present in 17 cases (12%), was second in group 2; and Chlamydia pneumoniae, present in 12 cases (8%), was second in group 3 . Etiology could not be determined on the basis of clinical presentation; identifying the etiology had no impact on mortality . Some findings were associated with specific causative organisms and outcome . A significantly lower number of nonsurvivors received adequate therapy (50% vs 77%) . CONCLUSIONS: Age, comorbidities, alcohol abuse, and smoking were related with distinct etiologies . PaO(2) to fraction of inspired oxygen ratio < 250, aerobic Gram-negative pathogen, chronic renal failure, Glasgow score < 15, malignant neoplasm, and aspirative pneumonia were associated with mortality by multivariate analysis . Local microbiologic data could be of help in tailoring therapeutic guidelines to the microbiologic reality at different settings . The stratification schema and the clinical rule used for hospitalization were useful. Antimicrob Agents Chemother, 2000 Dec, 44(12), 3272 - 7 In vitro and In vivo activities of LB 10827, a new oral cephalosporin, against respiratory pathogens; Paek KS et al.; The in vitro antibacterial activities of LB 10827, a new oral cephalosporin, against common respiratory tract pathogens were compared with those of six beta-lactams (cefdinir, cefuroxime, cefprozil, penicillin G, amoxicillin-clavulanate, and ampicillin), two quinolones (trovafloxacin and ciprofloxacin), and one macrolide (clarithromycin) . The MIC of LB 10827 at which 90% of the penicillin-resistant strains of Streptococcus pneumoniae tested were inhibited was 0.5 microg/ml, and the drug was 4- to 32-fold more active than the compared beta-lactams . The potent activity of LB 10827 against Haemophilus influenzae and Moraxella catarrhalis was retained, and the presence of beta-lactamase in both strains had little effect on the in vitro activity of the compound . Time-kill studies revealed that LB 10827 had bactericidal activity against these respiratory pathogens . This agent reduced original counts of all pathogens tested by >/=3 log(10) CFU/ml at the MIC, and the regrowth was completely prevented for 12 h . The potent in vitro antibacterial activity of LB 10827 against respiratory pathogens has been proved in both mouse pneumonia and neutropenic rat models . These results strongly suggest that this agent has potential for the treatment of respiratory tract infections. Acta Otorhinolaryngol Belg, 2000, 54(3), 409 - 12 Bacteriology in disease: failure of a micro-ecological balance? Gordts F. Both aerobic (mainly alpha-haemolytic streptococci) and anaerobic micro-organisms (like Prevotella and Peptostreptococcus species) are able to interfere with the growth of potential pathogens such as group A beta-haemolytic streptococci, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis . The present paper reviews the application of this concept of interference with respect to the development of common acute ear-, nose- and throat infections. J Theor Biol, 2000 Dec 7, 207(3), 349 - 59 Regulation of competence development in Haemophilus influenzae; Macfadyen LP; Development of competence for DNA uptake by the bacterium Haemophilus influenzae is tightly regulated, and expression of the cell's complement of competence genes is absolutely dependent on the cAMP-CRP complex . A second regulator of competence may maximize competence under starvation conditions . Several investigators have recently identified a consensus sequence (competence regulatory element, CRE) in the promoter regions of some competence genes and have proposed that this may be a binding site for Sxy (TfoX), a putative positive regulator of competence . However, a scoring method that reliably ranks candidate binding sites according to affinity for the cognate binding protein predicts that the cAMP-CRP complex will bind CRE sequences with high affinity . Moreover, the predicted Sxy protein lacks recognizable DNA-binding motifs and has not been shown to bind DNA . No other consensus sequences (putative binding sites) were identified in the promoter regions of competence genes . These observations suggest that the proposed competence-specific regulatory elements are in fact CRP-binding sites, and highlight the central role of cAMP-an established bacterial mediator of the response to nutritional stress-in competence regulation . Minor sequence elements uniquely conserved in the set of CRE sequences are predicted to reduce CRP affinity, and a model is suggested in which a secondary regulator of competence genes may interact with CRP under certain conditions to stabilize the initiation complex . Res Microbiol, 2000 Oct, 151(8), 669 - 81 Detection and subtyping of Actinobacillus pleuropneumoniae strains by PCR-RFLP analysis of the tbpA and tbpB genes; de la Puente-Redondo VA et al.; A PCR-based procedure for detection and serotype identification of Actinobacillus pleuropneumoniae strains was developed and evaluated . The A . pleuropneumoniae tbpA and tbpB genes were used as targets for amplification of DNA fragments, with a pair of specific primers for each gene . Amplification with tbpA primers rendered a 2.8-kb PCR product from all 12 A . pleuropneumoniae reference strains as well as from Actinobacillus suis strain CCM 5586, while amplification of a 1.9-kb PCR product was observed when testing ten Haemophilus parasuis strains of different serovars . Amplification of the tbpB gene from A . pleuropneumoniae serotypes 1, 6, 8 and 12, and A . suis CCM 5586 rendered an identical 1.8-kb fragment, while from A . pleuropneumoniae serotypes 2, 3, 4, 7, 9, 10 and 11, and H . parasuis strains it produced a 1.7-kb fragment . No PCR amplification product was observed when examining strains of 19 other swine pathogens or closely related species . The minimal detection limit for whole-cell A . pleuropneumoniae templates was between 5-50 and 3 x 10(2)-3 x 10(3) CFU when tbpA and tbpB specific primers, respectively, were used . Restriction fragment length polymorphism (RFLP) analysis of the PCR-generated products rendered different patterns, easily allowing us to discriminate between A . pleuropneumoniae, H . parasuis and A . suis and, more importantly, to distinguish ten RFLP A . pleuropneumoniae groups (the highest discrimination reported so far for a PCR assay with A . pleuropneumoniae), in such a way that the only serotypes with profiles identical to each other were 4 to 11 and 7 to 9 . Moreover, the PCR-RFLP analysis was assayed in 36 A . pleuropneumoniae field isolates and in porcine samples (lungs and nasal swabs from experimentally infected animals) . In both cases the system proved to be very efficient in A . pleuropneumoniae identification and serotype discrimination. Pol Merkuriusz Lek, 2000 Sep, 9 Suppl 1, 49 - 50 {Current status of immunization against Haemophilus influenzae type b in children in Poland}; Szenborn L et al.; The estimated incidence of Hib infections in Poland is about 29/100,000 children below 5 years of age (like in UK), the number of invasive infections particularly of purulent Hib meningitis is about 425-850 cases yearly . It indicates on necessity of immunisation against Haemophilus influenzae type B . The first own experience in vaccination with TetractHib or ActHib in 368 infants confirmed its safety in agreement with large studies of many foreign authors. J Public Health Med, 2000 Sep, 22(3), 337 - 42 Community Mothers Programme--seven year follow-up of a randomized controlled trial of non-professional intervention in parenting; Johnson Z et al.; BACKGROUND: The Community Mothers Programme aims at using experienced volunteer mothers in disadvantaged areas to give support to first-time parents in rearing their children up to 1 year of age . The programme was evaluated by randomized controlled trial in 1990 . METHODS: Seven years later, trial participants were interviewed about child health, nutrition, cognitive stimulation, parenting skills, and maternal self-esteem . The aim of this study was to see whether the demonstrated benefits at 1 year of age of this programme could be sustained at age 8 . RESULTS: One-third of the original group (38 intervention, 38 control), were contacted and interviewed . The risk for having an accident requiring a hospital visit was lower in the intervention group: relative risk (RR) 0.59, 95 per cent confidence interval (CI) 0.31-1.11 . Intervention children were more likely to visit the library weekly: RR 1.58, 95 per cent CI 1.10-2.26 . Intervention mothers were more likely to check homework every night: RR 1.23, 95 per cent CI 1.05-1.43 (p=0.006); and to disagree with the statement 'children should be smacked for persistently bad behaviour': RR 2.11, 95 per cent CI 1.10-4.06 . They were more likely to disagree with the statement 'I do not have much to be proud of': RR 1.24, 95 per cent CI 1.04-1.40; and to make a positive statement about motherhood than controls: RR 1.53, 95 per cent CI 1.06-2.20 . Subsequent children of intervention mothers were more likely to have completed Haemophilus influenzae b: RR 1.26, 95 per cent CI 1.06-1.51; and polio immunization: RR 1.19, 95 per cent CI 1.02-1.40 . CONCLUSIONS: The Community Mothers programme had sustained beneficial effects on parenting skills and maternal self-esteem 7 years later with benefit extending to subsequent children. Emerg Infect Dis, 2000 Nov-Dec, 6(6), 622 - 30 Risk factors for otitis media and carriage of multiple strains of Haemophilus influenzae and Streptococcus pneumoniae; St Sauver J et al.; We studied genetic diversity in Streptococcus pneumoniae and Haemophilus influenzae in throat culture isolates from 38 children attending two day-care centers in Michigan . Culture specimens were collected weekly; 184 S . pneumoniae and 418 H . influenzae were isolated from the cultures . Pulsed-field gel electrophoresis identified 29 patterns among the S . pneumoniae isolates and 87 among the H . influenzae isolates . Of the cultures, 5% contained multiple genetic types of S . pneumoniae, and 43% contained multiple types of H . influenzae . Carriage of multiple H . influenzae isolates, which was associated with exposure to smoking, history of allergies, and age 36 to 47 months, may increase risk for otitis media in children. West Indian Med J, 2000 Sep, 49(3), 200 - 4 Epidemiology of Haemophilus influenzae invasive disease in Jamaica, 1990-1993; Barton-Forbes MA et al.; Haemophilus influenzae (H influenzae) invasive disease was studied retrospectively over a four-year period in children admitted to the Bustamante Hospital for Children in Kingston, Jamaica . A total of 86 cases were identified . The mean estimated annual incidence of H influenzae invasive disease in Kingston and St Andrew was 39 per 100,000 children under 5 years of age . The majority (77%) of cases were in the under 2-year age group . A distinct seasonal pattern was noted, with a significantly higher proportion of patients (57-73%) presenting in the cooler months . Meningitis was the most common clinical diagnosis, accounting for 76% of the cases . Poor outcome was demonstrated in 21.5% of patients with meningitis . Sensitivity testing of H influenzae isolates revealed a resistance rate of 26% for ampicillin and 7% for chloramphenicol . The epidemiological findings in this study provide reasonable guidelines for empiric antibiotic therapy and also support the need to seriously consider vaccine prophylaxis in Jamaican children. J Biol Chem, 2001 Feb 16, 276(7), 5296 - 302 Epub 2000 Nov 13. The Haemophilus ducreyi cytolethal distending toxin induces cell cycle arrest and apoptosis via the DNA damage checkpoint pathways; Cortes-Bratti X et al.; The cytolethal distending toxins (CDTs) induce cell cycle arrest by a mechanism still not well characterized . We demonstrate that the effect of the Haemophilus ducreyi CDT (HdCDT) is cell type-specific: B cell lines underwent apoptosis, epithelial cells and keratinocytes arrested exclusively in G(2), whereas normal fibroblasts arrested both in G(1) and G(2) . We studied normal keratinocytes and fibroblasts, which are relevant for understanding the pathogenicity of H . ducreyi . The response to HdCDT resembles the checkpoint response activated by ionizing radiation . Both responses were characterized by an early induction of the p53 gene and the cyclin-dependent kinase inhibitor p21 in fibroblasts, and activation of the chk2 kinase in epithelial cells . In the Ataxia Telangiectasia-mutated gene (ATM)-deficient lymphoblastoid cell lines, intoxication was significantly delayed compared with ATM wild type cells, and was associated with a slower kinetic of p53 stabilization, suggesting that the early response to HdCDT is ATM-dependent . Activation of ATM-dependent pathways was further confirmed by the ability of caffeine to partially override the HdCDT-mediated cell cycle arrest . Our data shed new light on the mechanism of action of this novel family of bacterial toxins, limiting the target candidates to DNA or molecules directly involved in activation of checkpoint responses. Int J Pediatr Otorhinolaryngol, 2000 Nov 30, 56(1), 23 - 31 Acute otitis media: bacteriology and bacterial resistance in 205 pediatric patients; Commisso R et al.; Acute otitis media (AOM) is one of the most frequent diagnoses in children below the age of 2 years . Treatment is usually based on information included in the literature concerning bacteriology . The purpose of this work was to define the most frequent germs in the etiology of AOM within our community, in order to optimize therapeutics for this pathology . Cultures in middle ear secretions obtained through tympanocentesis were performed to this end, ensuring careful sample taking and processing . The results obtained are similar to those published in previous papers for which Streptococcus pneumoniae and Haemophilus influenzae proved to be the predominant germs . However, there are certain discrepancies concerning the incidence of Moraxella catarrhalis and this has a direct impact on the total percent of resistant strains, thus modifying therapeutic approaches for treatment of AOM . The antibiotic sensitivity profiles of the most frequent etiologic agents were studied in accordance with the principles established by the 'National Committee for Clinical Laboratory Standards' (NCCLS). Lab Anim, 2000 Oct, 34(4), 409 - 12 Transmission of rat and guineapig Haemophilus spp . to mice and rats; Boot R et al.; Mice and rats, free from Pasteurellaceae, were exposed to Haemophilus spp . (V-factor dependent Pasteurellaceae) by housing in proximity to infected rats or guinea pigs, and monitored by culture and enzyme-linked immunosorbent assay (ELISA) for cross infection . A minority of mice became infected when exposed to Haemophilus-infected rats but none when exposed to guinea pigs . Rats were readily infected when exposed to Haemophilus-infected guinea pigs or rats . Although Pasteurellaceae infections are commonly considered as host specific, our data show that Haemophilus spp . can cross the species barrier from rats to mice and from guinea pigs to rats. Jpn J Antibiot, 2000 Aug, 53(8), 566 - 72 {Antibacterial activities of piperacillin for several resistant strains from respiratory infections--in reference to MRSA, PRSP, BLNAR and P . aeruginosa}; Matsuzaki K et al.; We investigated antibacterial activities of piperacillin (PIPC) for several resistant strains of bacteria isolated from patients with respiratory infections from 1998 to 1999 in comparison with reference drugs and obtained the following results: 1 . The majority of methicillin resistant strains of Staphylococcus aureus (MRSA) showed high resistance to beta-lactam antibiotics including PIPC . 2 . MIC90 of PIPC was 1 and 4 micrograms/ml for penicillin intermediate and penicillin resistant strains of Streptococcus pneumoniae (PISP/PRSP), respectively . 3 . MIC90 of PIPC was 0.25 microgram/ml for beta-lactamase negative ampicillin resistant strains of Haemophilus influenzae (BLNAR), showing higher antibacterial activity than the reference drugs . 4 . PIPC exhibited the MICs of 8 micrograms/ml or less in 19 out of 40 IPM resistant (MIC > or = 16 micrograms/ml) strains of Pseudomonas aeruginosa . From these results, PIPC is proved to possess extremely favorable antibacterial activities for BLNAR, and it was suggested that PIPC might be a drug of choice even for PISP/PRSP and IPM resistant strains of P . aeruginosa. Respiration, 2000, 67(5), 552 - 8 Inhibitory effect of N-acetylcysteine on adherence of Streptococcus pneumoniae and Haemophilus influenzae to human oropharyngeal epithelial cells in vitro; Riise GC et al.; BACKGROUND: Bacterial adherence to mucosal and epithelial cell structures is of importance for the persistence of bacteria in the airways . Cigarette smoking and chronic bronchitis are associated with increased bacterial adherence . N-Acetylcysteine (NAC) medication reduces the number of infectious exacerbations in patients with chronic bronchitis, and NAC medication has been associated with low intrabronchial bacterial numbers . OBJECTIVE: We investigated whether NAC influences bacterial adherence as a possible mechanism behind its clinical effects . METHODS: Highly adhering test strains of Streptococcus pneumoniae and Haemophilus influenzae were used to investigate the influence of four pharmacological compounds on adherence to oropharyngeal epithelial cells in vitro . Adhesion assays were performed both during short-term exposure to, as well as after long-time incubation with, NAC, lidocaine, hydrocortisone and terbutaline at concentrations not inhibiting bacterial growth . RESULTS: Only NAC showed a significant inhibitory effect on adhesion of H . influenzae during short-term incubation . After long-term incubation, both NAC and hydrocortisone inhibited bacterial adhesion for both strains in a dose-dependent manner . When NAC's effect on three different strains of S . pneumoniae and four strains of H . influenzae was studied, inhibition of bacterial adhesion was found for three strains of each species . CONCLUSIONS: NAC lowers bacterial adhesion in vitro to oropharyngeal epithelial cells in doses equivalent to that is being used clinically . This effect might be a contributory mechanism behind the reduction of infectious exacerbations in chronic bronchitis patients . Rev Prat, 2000 Sep 15, 50(14), 1531 - 5 {Acute rhinosinusitis and sinusitis}; Gehanno P; During the common cold in the adult, involvement of the sinusal mucosa, confirmed by CT scan, is virtually constant and justifies the term "rhinosinusitis" that is now applied . The presence of bacterial superinfection can only be demonstrated by positive laboratory results on a sample, which is never performed in usual practice; thus the practitioner must rely on presumptive factors . Among them, an essential element is the unilateral nature of painful symptoms and purulent rhinorrhoea . When symptoms are bilateral, antibiotics should not be prescribed except when the condition has not been resolved by symptomatic treatment during several days . In such cases, other important discriminating factors are also examination showing pus originating from below the middle meatus or sinusal X-ray showing a liquid level or a total opacity . On the other hand, clinical suspicion of localisation of infection in the frontal or sphenoid sinuses unquestionably requires rapid antibiotic treatment . Presently the choice of antibiotic tends toward products active on both Haemophilus producing beta-lactamase and on pneumococci with reduced sensitivity to penicillin having only a low level of resistance. JAMA, 2000 Nov 8, 284(18), 2334 - 40 Antibody concentration and clinical protection after Hib conjugate vaccination in the United Kingdom; Heath PT et al.; CONTEXT: The schedule for Haemophilus influenzae type b (Hib) vaccination of infants in the United Kingdom consists of 3 doses given at 2, 3, and 4 months of age . Many countries include a fourth dose (booster) of Hib vaccine in the second year of life on the basis of declining Hib antibody concentrations after the primary series . Few data are available to show that this fourth dose is actually necessary . OBJECTIVE: To evaluate long-term clinical protection against Hib disease and Hib antibody concentrations following primary Hib vaccination without a booster dose . DESIGN, SETTING, AND SUBJECTS: Clinical protection study conducted between October 1992 and March 1999 in the United Kingdom, in which children developing invasive Hib disease despite vaccination in infancy with 3 doses of Hib conjugate vaccine were reported by pediatricians through an active, prospective, national survey . Separate antibody studies were conducted among 2 cohorts of children (n = 153 and n = 107) vaccinated at 2, 3, and 4 months of age with Hib conjugate vaccine and followed up to 43 and 72 months of age . MAIN OUTCOME MEASURES: Age-specific vaccine effectiveness, derived from the observed number of true vaccine failures after 3 Hib vaccine doses compared with the number of cases expected based on the age-specific rates of invasive Hib disease obtained prior to the introduction of Hib vaccines; and proportion of children in the 2 cohorts with Hib antibody concentrations of less than 0.15 and less than 1.0 microg/mL . RESULTS: Ninety-six true vaccine failures occurring after 3 vaccine doses were detected . During the study period, an estimated 4,368,200 infants in the United Kingdom received 3 doses of vaccine; therefore, the vaccine failure rate was 2.2 per 100,000 vaccinees (95% confidence interval, 1.8-2.7 per 100,000) . Although vaccine effectiveness declined significantly after the first year of life (P<.001), it remained high until the sixth year of life (99.4% in children aged 5-11 months vs 97.3% in those aged 12-71 months) . The proportion of cohorts 1 and 2 with anti-PRP antibody levels of less than 0.15 microg/mL increased between 12 and 72 months of age (6% at 12 months, 8% at 43 months, and 32% at 72 months; chi(2)(1) = 18.25; P<.001 for trend) . CONCLUSIONS: Our results suggest that anti-PRP antibody levels and clinical protection against Hib disease wane over time after Hib vaccination at 2, 3, and 4 months of age without a booster dose at 2 years of age . The decline in clinical protection is minimal, however, suggesting that a booster dose of Hib vaccine following infant vaccination is not essential . JAMA . 2000;284:2334-2340. Braz J Infect Dis, 2000 Oct, 4(5), 245 - 54 Prevalence of antimicrobial resistance among respiratory tract isolates in Latin America: results from SENTRY antimicrobial surveillance program (1997-98); Sader HS et al.; One thousand seventy-three bacterial isolates were collected from patients with community acquired respiratory tract infections (CARTI) in 11 Latin American centers (7 countries) during 1997 and 1998 . They were tested against numerous antimicrobial agents by the reference broth microdilution method as part of the ongoing multinational SENTRY Antimicrobial Surveillance Program . Among Streptococcus pneumoniae (553 isolates), approximately 61% were susceptible to penicillin . There was a great variation of the penicillin susceptibility rates among participating countries . The highest susceptibility rates were found in Argentina (76.7%) and Brazil (71.9%), while the lowest rate of penicillin susceptibility was detected in Mexico (33.3%) . High level resistance to penicillin and resistance to cefotaxime were observed in nearly 10% of the isolates . The newer quinolones, levofloxacin (MIC(90) 2 microg/mL) and gatifloxacin (MIC90 0.5 microg/mL), were active against 100% of the isolates tested . Among the other non-beta-lactams drugs tested, the rank order of susceptibility against the pneumococci was: chloramphenicol (93.9%)>clindamycin (93.2%)> azithromycin (89.1%) > clarithromycin (88.7%)>tetracycline (78.5%)> trimethoprim/sulfamethoxazole (55.7%) . The percentage of Haemophilus influenzae (361 isolates) isolates resistant to amoxicillin was 12 . 7% (beta-lactamase positive) . Among Moraxella catarrhalis (159 isolates) isolates, only 8.2% were susceptible . Clavulanic acid restored the activity of amoxicillin against both species . Trimethoprim/sulfamethoxazole was active against only 59.5% of H . influenzae, while susceptibility to this compound among M . catarrhalis was 96.1% . All other compounds tested were active against>95% of H . influenzae and M . catarrhalis isolates . These species were susceptible to levofloxacin (MIC90 < or = 0.5 microg/mL for both) and gatifloxacin (MIC90 < or = 0.03 microg/mL for both) with very low MICs . Our results indicate that penicillin resistance rates are particularly high among pneumococci in some countries . The newer fluoroquinolones show an excellent potency and spectrum against pathogens causing community acquired respiratory infections in Latin America. Med J Aust, 2000 Oct 2, 173 Suppl, S54 - 7 Conjugate pneumococcal vaccines for non-indigenous children in Australia; McIntyre PB et al.; Childhood pneumococcal disease is associated with substantial morbidity and mortality, but total disease burden is more difficult to measure than for invasive disease caused by Haemophilus influenzae type b (Hib) . A safe, effective seven-valent conjugate pneumococcal vaccine will be available in Australia by early 2001, and will certainly be indicated for high-risk groups and purchased in the private sector, as was Hib vaccine . The status of this vaccine on the Australian Standard Vaccination Schedule will require more detailed consideration of the burden and serotype distribution of pneumococcal disease in Australian children and the vaccine's likely cost-effectiveness . Postmarketing surveillance will be particularly important. Kurume Med J, 2000, 47(3), 205 - 10 In vitro susceptibilities to 23 antimicrobial agents of Haemophilus influenzae from pediatric patients in Japan; Matsuo Y; One hundred eighty-six clinical isolates of Haemophilus influenzae (H . influenzae) collected from January 1996 through December 1997 from 182 pediatric patients and 16 isolates from blood or cerebrospinal fluid (CSF) of 13 patients with bacteremia and purulent meningitis collected during the last ten years were examined for in vitro susceptibilities to 23 antibiotic agents, including 3 penicillins, 9 cephalosporins, 4 carbapenems and others, as well as for their encapsulated types and beta-lactamase production . Ceftriaxone (a third generation cephalosporin) had the highest activity against the strains in this study (minimal inhibitory concentration, MIC90 of 0.025 microgram/ml) and cefditoren (a new oral cephalosporin) was the most active oral antimicrobial agent (MIC90 of 0.05 microgram/ml) . Meropenem had a much higher activity against H . influenzae (MIC90 of 0.2 microgram/ml) than the other carbapenems (imipenem, MIC90 of 1.56 micrograms/ml, panipenem, MIC90 of 1.56 micrograms/ml, and biapenem, MIC90 of 3.13 micrograms/ml) . Regarding the serotyping of the encapsulated strains, 172 strains (85.1%) were nontypeable and 30 (14.9%) were serotyped (24 strains of type b, 4 strains of type e, one each of type a and c) . Fifteen of the strains isolated from blood and CSF were type b and one was nontypeable . Sixteen of 202 strains (7.9%) produced beta-lactamase and all of them produced both penicillinase and cephalosporinase . The production of beta-lactamase in this study was lower than that reported in previous studies {1-3} . In this study, some strains were found against which the MICs of carbapenems were very high (highest MIC of imipenem was 12.5 micrograms/ml, of panipenem was 6.25 micrograms/ml and of biapenem was 25 micrograms/ml) . Therefore, we assayed the binding affinities of imipenem for each of penicillin-binding proteins (PBPs) about one of these resistant strains . In resistant strains, inhibitory concentrations (IC50) of imipenem for PBP4 and 5 were much higher than those in susceptible strains . Thus, the results demonstrate the decrease of the affinity of imipenem for PBP4 and 5 . It seems, therefore, that the major factor in the resistance to imipenem of H . influenzae was the low affinity of PBP4 and 5 for the drug. Pediatr Infect Dis J, 2000 Oct, 19(10), 1000 - 4 Risk factors for sternal wound and other infections in pediatric cardiac surgery patients; Mehta PA et al.; BACKGROUND: This study was undertaken to determine the incidence, pathogens and risk factors associated with development of sternal wound and other infections in children undergoing cardiac surgery . METHODS: Retrospective chart review was performed for all cardiac surgeries performed on children <18 years of age at Upstate Medical University at Syracuse between January, 1996, and June, 1998 . For evaluation of risk factors for sternal wound infection, only patients undergoing sternotomy are included in the analysis: those with infection are compared with those without for preoperative, intraoperative and postoperative risk factors . RESULTS: Sternal wound infection developed in 10 of 202 (5%) children after median sternotomy . Superficial sternal wound infection developed in 6 (3%) children, and 4 (2%) had deep infection . Children with sternal wound infection had lower age, higher American Society of Anesthesiologist score, longer preoperative stay, longer period of ventilation and inotropic support, longer intensive care unit and total postoperative hospital stays and increased leukocyte band cell counts preoperatively and on Postoperative Day 1 than those without sternal infection . Causative agents for sternal wound infection were Staphylococcus aureus (6), Pseudomonas aeruginosa (1) and Haemophilus influenzae non-type b (1) . In addition 32 bacterial infections occurred at nonsurgical sites after 28 procedures . Infections included pneumonia, urinary tract infection and bacteremia . Longer bypass time and longer operation time were two additional risk factors for nonwound infection . CONCLUSION: Infections continue to be a significant cause of morbidity in cardiac surgery patients . Knowledge of risk factors for infection could be useful in preventive and treatment strategies for these high-risk groups. Neuropsychology, 2000 Oct, 14(4), 509 - 18 Longitudinal outcomes of Haemophilus influenzae meningitis in school-age children; Taylor HG et al.; The purpose of this study was to investigate long-term outcomes of Haemophilus influenzae Type b meningitis in a cohort of school-age survivors . Findings from an initial assessment at mean age 10 years revealed neuropsychological, achievement, and behavioral sequelae in the children with neurologic complications during the acute-phase illness (H . Taylor, C . Schatschneider, & D . Rich, 1992) . Here, the cohort was reassessed 1 and 2 years after the initial evaluation to investigate age-related influences on disease sequelae . After excluding children with hearing loss, the sample was divided into 2 groups: an affected group of 39 children with acute-phase neurologic complications and an unaffected group of 73 children without these complications . Growth-curve modeling showed poorer outcomes at the final assessment and less rapid improvement at follow-up for the affected group . Later age at assessment and later age at illness were associated with larger group differences in some outcomes . Results suggest that children with diffuse early brain insults are at risk for later-emerging sequelae. Chemotherapy, 2000 Nov-Dec, 46(6), 379 - 82 In vitro activity of moxifloxacin(BAY 12-8039) against respiratory tract pathogens from six Latin-American countries; Cardenosa G O et al.; The in vitro antibacterial activity of moxifloxacin (BAY 12-8039) was evaluated against 636 isolates of respiratory tract pathogens . The isolates were collected from July 1997 to August 1998 in the frame of a multinational Latin American study . E-test strips calibrated to read moxifloxacin MIC ranges from 0.002 to 32 microg/ml were used in susceptibility testing . Weekly quality control tests in each laboratory ensured reproducibility . Laboratories from Argentina, Brazil, Chile, Colombia, Mexico and Uruguay participated . MIC(90) for moxifloxacin were as follows: Streptococcus pneumoniae (304 isolates) 0.25 microg/ml, Haemophilus influenzae (135 isolates) 0.125 microg/ ml, Streptococcus pyogenes (66 isolates) 0.25 microg/ml, Moraxella catarrhalis (62 isolates) 0 . 25 microg/ml and methicillin-sensitive Staphylococcus aureus (69 isolates) 0.25 microg/ml . These results agreed with reports from other areas . Moxifloxacin showed excellent activity against respiratory pathogens from participant countries . Lancet, 2000 Oct 21, 356(9239), 1398 - 402 Treatment of acute otitis media with an antiadhesive oligosaccharide: a randomised, double-blind, placebo-controlled trial; Ukkonen P et al.; BACKGROUND: Antiadhesive compounds are promising candidates for prevention or treatment of infections . We have investigated the efficacy of such an agent, 3'-sialyllacto-N-neotetraose (NE-1530), given intranasally for prophylaxis of acute otitis media and for effect on nasopharyngeal carriage of bacteria . METHODS: We did a randomised, double-blind placebo-controlled study at one study site . 507 healthy children were randomly assigned either NE-1530 (n=254) or placebo (253) as intranasal sprays twice daily during 3 months . The children were examined by the study physicians once a month and during illness . Treatment efficacy was estimated from Cox proportional hazards model . A sample of nasopharyngeal secretion was taken at every visit for culture of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis . Adverse events were recorded in study diaries . FINDINGS: At least one event of acute otitis media was diagnosed in 108 (43%) of 254 children in the NE-1530 group and in 86 (34%) of 253 children in the placebo group . The efficacy of treatment was negative, -27% (95% CI -68 to 5; p=0.10) . The nasopharyngeal carriage of S pneumoniae, H . influenzae, and M . catarrhalis was not affected by treatment, and the adverse event profiles were almost identical for NE-1530 and placebo . INTERPRETATION: NE-1530 did not have a beneficial effect on the occurrence of acute otitis media or on the nasopharyngeal carriage of bacteria in children. Semin Respir Infect, 2000 Sep, 15(3), 234 - 47 Antibiotic therapy in acute exacerbations of chronic bronchitis; Adams SG et al.; Chronic obstructive pulmonary disease (COPD) comprises a spectrum of conditions including chronic bronchitis, emphysema, asthma, and bronchiectasis . It has a prevalence in the United States of 5.1% to 5.4% in the middle-aged to elderly population, with a lower rate in nonsmoking individuals . Moreover, COPD is complicated by frequent and recurring acute exacerbations of chronic bronchitis (AECB) . Overall, COPD represents the fourth leading cause of mortality in the United States and is the second leading cause of work disability . This condition is also associated with high morbidity and health care expenditures . Despite the controversy over the need to prescribe antibiotics for patients with AECB, high-risk patients have been identified who will benefit from this therapy.These include, patients with a history of repeated infections (>4 per year), comorbid illnesses (such as diabetes, asthma, coronary heart disease), or marked airway obstruction . Furthermore, a bacterial cause is shown in approximately 50% of AECB episodes, and primarily includes Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae . Additionally, resistance among community-acquired respiratory pathogens in the United States has risen dramatically, with beta-lactamase production evident in 40% of H . influenzae and greater than 95% of M . catarrhalis isolates, and with approximately 10% of pneumococci highly resistant to penicillin and simultaneously resistant to macrolide antibiotics . The criteria used to make choices for antibiotic use in patients with AECB should include knowledge of the frequencies of pathogen resistance and patients' clinical characteristics . An effective antibiotic, however, must be able to rapidly resolve the acute infection with the least patient morbidity and need for hospitalization . Although there remains controversy as to when to initiate antibiotic therapy in patients with AECB, several guidelines have been published. Semin Respir Infect, 2000 Sep, 15(3), 208 - 15 Evidence of bacterial infection in acute exacerbations of chronic bronchitis; Wilson R; The frequency with which bacterial infection causes exacerbations of chronic obstructive pulmonary disease (COPD) may depend on the dominant pathology present; patients with chronic bronchitis are more susceptible to bacterial bronchial infections than those at the emphysema or asthma ends of the spectrum . However, impairment in respiratory function may be very important in governing the outcome of an exacerbation . Placebo-controlled trials have provided conflicting evidence of the efficacy of antibiotics in acute exacerbations . Overall, there is a significant benefit, particularly in certain patient groups, defined by symptoms and past history . Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis are the species most commonly isolated during exacerbations, and the same species may colonize the bronchial mucosa when the patient is in a stable state . Evidence is accumulating that bacteria are an independent stimulus of mucus hypersecretion and bronchial inflammation, and that they interact with other stimuli such as viral infection, atmospheric pollution, and tobacco smoke . New approaches are being used to investigate the importance of bacterial infection in patients with COPD.There are several good reasons why new more potent antibiotics might be expected to be superior to older standard compounds in the management of patients with problematic COPD . However, future studies should aim to confirm that bacteriologic superiority translates into improved clinical outcomes, and seek to measure the level of benefit. Semin Respir Infect, 2000 Sep, 15(3), 195 - 207 Antimicrobial susceptibility patterns of respiratory pathogens--a global perspective; Blondeau JM et al.; Antimicrobial resistance among respiratory tract pathogens poses a major challenge for the ongoing use of antimicrobial agents for treating infected patients . Global antimicrobial susceptibility data has documented the existence of widespread resistance issues . Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis constitute the principal community-acquired respiratory tract bacterial pathogens . For H . influenzae, resistance to ampicillin varies from less than 5% in some European countries to greater than 30% in North America and Southeast Asia . For H . influenzae, resistance to trimethoprim/sulfamethoxazole has been shown to range from less than 5% in North America and Europe to greater than 25% in Europe, the Middle East, and India . For M . catarrhalis, 85% to 100% of isolates worldwide are beta-lactamase positive and, therefore, ampicillin and amoxicillin resistant . Penicillin-resistant S . pneumoniae shows considerable variability worldwide ranging from 6% to 80% whereas macrolide resistance among the pneumococci range from 0% to 90% . Clearly, documenting and understanding the emergence, dissemination, and infection with pathogens resistant to antimicrobial agents is essential for developing strategies to deal with this global problem . This article highlights the frequency of antimicrobial resistance among the respiratory pathogens from a global perspective . Also, mechanisms of resistance and factors associated with the emergence, dissemination, and colonization of resistant organisms are discussed. J Antimicrob Chemother, 2000 Sep, 46 Suppl 1, 59 - 62; discussion 63-5 Ecological antibiotic policy; Hoiby N; Development of resistance to antibiotics is a major problem worldwide . The normal oropharyngeal flora, the intestinal flora and the skin flora play important roles in this development . Within a few days after the onset of antibiotic therapy, resistant Escherichia coli, Haemophilus influenzae and Staphylococcus epidermidis can be detected in the normal flora of volunteers or patients . Horizontal spread of the resistance genes to other species, e.g . Salmonella spp., Staphylococcus aureus and Streptococcus pneumoniae, occurs by conjugation or transformation . An ecologically sound antibiotic policy favours the use of antibiotics with little or no impact on the normal flora . Prodrug antibiotics which are not active against the bacteria in the mouth and the intestine (before absorption) and which are not excreted to a significant degree via the intestine, saliva or skin are therefore preferred . Prodrugs such as pivampicillin, bacampicillin, pivmecillinam and cefuroxime axetil are favourable from an ecological point of view . Experience from Scandinavia supports this, since resistance to mecillinam after 20 years of use is low (about 5%) and stable. Semin Neurol, 2000, 20(3), 293 - 306 Acute bacterial meningitis; Roos KL; In the past 10 years the epidemiology of bacterial meningitis has changed, with a decreased incidence of meningitis caused by Haemophilus influenzae and an increasing incidence of meningitis caused by penicillin- and cephalosporin-resistant strains of Streptococcus pneumoniae . Meningococcal meningitis has become an increasing threat to college students . Successful outcome from meningitis requires not only eradication of the bacterial pathogen but also management of the neurological complications of raised intracranial pressure, stroke, and seizure activity . In this article, the pathophysiology, etiology, clinical presentation, differential diagnosis, and management of acute bacterial meningitis are reviewed . The present recommendations for the use of dexamethasone in the treatment of this infection, the use of chemoprophylaxis, and the indications for vaccinations are included. Clin Infect Dis, 2000 Oct, 31(4), 973 - 80 Epub 2000 Oct 25. Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood; Heath PT et al.; Haemophilus influenzae type b (Hib) conjugate vaccines have proved extremely efficacious in healthy children . True Hib vaccine failures are rare . Hib conjugate vaccines were introduced for routine immunization in the United Kingdom and the Republic of Ireland in 1992 . Coincident with this, active prospective and national surveillance via pediatricians, microbiologists, and public health physicians was commenced to assess the clinical and immunological factors associated with vaccine failure . During the 6 years of the study, 115 children with true vaccine failure were reported . Of the children who were vaccinated before 12 months of age, a clinical risk factor was detected in 20%, an immunological deficiency was detected in 30%, and one or both were detected in 44% . Children who were vaccinated after 12 months of age were more likely to have one or both factors (67%) . Thirty percent (33 of 105) of children with true vaccine failure had a low Hib antibody response (concentration, <1.0 microg/mL) after disease, but the majority then responded to a further dose of Hib vaccine . Children who develop Hib disease despite vaccination deserve further clinical and immunological evaluation. Clin Infect Dis, 2000 Oct, 31(4), 875 - 80 Epub 2000 Oct 25. Effects of amoxicillin/clavulanate or azithromycin on nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae in children with acute otitis media; Ghaffar F et al.; The effect of antibiotic therapy on nasopharyngeal colonization by Streptococcus pneumoniae and Haemophilus influenzae was evaluated in children diagnosed with acute otitis media . Children were randomly assigned to receive either amoxicillin/clavulanate or azithromycin therapy, and nasopharyngeal swabs were obtained for culture before and after starting therapy . Amoxicillin/clavulanate therapy eradicated or suppressed all strains of S . pneumoniae susceptible to penicillin, 75% of strains with intermediate resistance, and 40% of strains resistant to penicillin . Azithromycin therapy cleared two-thirds of azithromycin-susceptible strains of S . pneumoniae but none of azithromycin-nonsusceptible strains . Selection for antibiotic-resistant strains in individual children was not observed in children who received amoxicillin/clavulanate therapy but was observed in 2 children who received azithromycin therapy . Carriage of H . influenzae was also reduced by antimicrobial therapy but more so by amoxicillin/clavulanate . Antibiotic therapy does not directly increase the number of resistant strains in the population but, by eradicating susceptible strains, allows greater opportunity for carriage and spread of resistant strains. Clin Infect Dis, 2000 Oct, 31(4), 869 - 74 Epub 2000 Oct 12. Prospective study of the usefulness of sputum Gram stain in the initial approach to community-acquired pneumonia requiring hospitalization; Roson B et al.; From February 1995 through May 1997, we prospectively studied 533 patients with community-acquired pneumonia requiring hospitalization in order to assess the current usefulness of sputum Gram stain in guiding the etiologic diagnosis and initial antibiotic therapy when applied routinely . Sputum samples of good quality were obtained in 210 (39%) patients, 175 of whom showed a predominant morphotype . Sensitivity and specificity of Gram stain for the diagnosis of pneumococcal pneumonia were 57% and 97%, respectively; the corresponding values for Haemophilus influenzae pneumonia were 82% and 99% . Patients with a predominant morphotype were more frequently treated with monotherapy than were patients without a demonstrative sputum sample (89% vs . 75%; P<.001) . Analysis of our data shows that a good-quality sputum sample can be obtained from a substantial number of patients with community-acquired pneumonia . Gram stain was highly specific for the diagnosis of pneumococcal and H . influenzae pneumonia and may be useful in guiding pathogen-oriented antimicrobial therapy. Eur J Epidemiol, 2000 Jun, 16(6), 521 - 6 Prevalence of Haemophilus influenzae pharyngeal carriers in the school population of Catalonia . Working Group on invasive disease caused by Haemophilus influenzae; Bou R et al.; The objective of this study was to determine the prevalence of healthy Haemophilus influenzae (Hi) pharyngeal carriers in a representative sample of the Catalonian school population, as well as the factors associated . A two-stage cluster sampling was carried out . Parents were given a questionnaire to collect information on sociodemographic and epidemiological variables . A pharyngeal swab was performed on children when informed consent was given by parents, and was cultured on chocolate agar with 260 microg/ml bacitracin . Of the 1212 children studied, 316 (26%) H . influenzae carriers were detected: 5 (0.4%) serotype b, 1 (0.08%) serotype c, 6 (0.5%) serotype e, 5 (0.4%) serotype f, and 299 (24.7%) non-typable . Age, gender and geographical location were the only variables associated with H . influenzae carrier status . The prevalence of non-typable H . influenzae carriers was similar to that of studies carried out in other countries, while that of serotype b carriers was similar to the remainder of H . influenzae capsulates, and lower than that described in previous studies . These data are in accordance with the low incidence of the disease observed in our context, although the possibility that the vaccine coverage may have affected the results of this study cannot be dismissed. Trop Med Int Health, 2000 Oct, 5(10), 711 - 21 Antibiotic medication and bacterial resistance to antibiotics: a survey of children in a Vietnamese community; Larsson M et al.; OBJECTIVE: To investigate antibiotic use and antibiotic susceptibility of respiratory tract pathogens in children aged 1-5 years in Bavi, Vietnam . METHOD: Nasopharynx and throat specimens were collected from 200 children from randomly selected households in a demographically defined population . Respiratory isolates were tested for antibiotic susceptibility according to the standard disk diffusion method . A questionnaire survey of carers elicited information on type of antibiotic used, duration of treatment, where the antibiotics had been purchased, type of treatment information retained by carers and episodes of illness preceding the study . RESULTS: 82% of the children had at least one symptom of acute respiratory tract infection (ARI) in the 4 weeks prior to the study, and of these 91% were treated with antibiotics . The most commonly used antibiotics were ampicillin (74%), penicillin (12%), amoxicillin (11%), erythromycin (5%), tetracycline (4%) and streptomycin (2%) . Ampicillin was used for 3.3 days on average (SD:1.8) and penicillin for 2.6 days (SD:0.7) . When deciding which antibiotic to use, 67% of the carers consulted the pharmacy seller, 11% decided themselves and 22% followed the doctor's prescription . The carrier rate of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis was 50%, 39% and 17%, respectively . Isolates from 145 children were susceptibility tested, and 74% were found to carry resistant pathogens . Of the tested isolates, 90% of S . pneumoniae, 68% of H . influenzae and 74% of M . catarrhalis were resistant to at least one antibiotic . The mean number of antibiotics (susceptible strains excluded) to which resistance was found was 2.0 (SD:1.2), 2.5 (SD:1.8) and 2.1 (SD:0.9), respectively . S . pneumoniae and H . influenzae showed high resistance to tetracycline (88% and 32%, respectively), trimethoprim/sulphonamide (32% and 44%), and chloramphenicol (25% and 24%) . 23% of S . pneumoniae were erythromycin-resistant and 18% of H . influenzae isolates were resistant to ampicillin . There was a significant difference in ampicillin and penicillin resistance between the group of children previously treated with beta lactam antibiotics and the group of children who did not receive antibiotics . CONCLUSION: As reported by the carers, children in Bavi are treated with antibiotics frequently . Most antibiotics were obtained without consulting a doctor . High levels of antibiotic resistance and high prevalence of multidrug-resistant strains were found among respiratory pathogens . The existence of a large reservoir of resistance genes among children in low-income countries represents a threat to the success of antibiotic therapy throughout the world . Multi-faceted programmes to improve rational use of antibiotics in Vietnam are urgently needed. WMJ, 2000 Aug, 99(5), 45 - 8 Impact of Haemophilus influenzae type b (Hib) conjugate vaccines on Haemophilus influenzae meningitis in Wisconsin; Enders PJ et al.; The first effective Haemophilus influenzae type b (Hib) conjugate vaccines were approved for use in children and infants between 1987 and 1990 . In 1993, the federal government began the Childhood Immunization Initiative (CII), a program to improve the rate of vaccination of children nationwide . Subsequently, the proportion of 19 to 35-month-old children who received three or more doses of Hib vaccine rapidly increased from 28% in 1992 to 90% by 1995, with a concurrent dramatic decline in the inci