J Clin Microbiol, 1999 Jun, 37(6), 2045 - 6 Use of Dorset egg medium for maintenance and transport of Neisseria meningitidis and Haemophilus influenzae type b; Wasas AD et al.; Studies of bacterial meningitis are hampered by the inability to maintain the viability of etiological agents during transport to reference laboratories . The long-term survival rate of 20 isolates of Neisseria meningitidis and Haemophilus influenzae type b (Hib) on Dorset egg medium, supplemented Columbia agar base medium, chocolate agar, and Amies medium was compared with that on 70% GC agar (chocolate) transport medium . N . meningitidis isolates were also inoculated onto 5% horse blood agar, and Hib was inoculated onto Haemophilus test medium . All of the N . meningitidis isolates remained viable on Dorset egg medium for 21 days; viability on the other media was poor after only 7 days . Recovery rates of Hib isolates were similar on Dorset egg and Haemophilus test media (100% after 21 days) and significantly better than on the other media . Dorset egg medium is inexpensive and easy to make and may be invaluable for studies of bacterial meningitis in developing countries. J Clin Microbiol, 1999 Jun, 37(6), 1999 - 2002 Activity of gatifloxacin against Haemophilus influenzae and Moraxella catarrhalis, including susceptibility test development, E-test comparisons, and quality control guidelines for H . influenzae; Jones RN et al.; In vitro antimicrobial activity and susceptibility testing interpretation criteria and quality control were studied for gatifloxacin, a new 8-methoxy fluoroquinolone, tested against Haemophilus influenzae . Moraxella catarrhalis (600 strains) and H . influenzae (1,400 strains) from the SENTRY Antimicrobial Surveillance Program in North America (Canada and the United States) were also tested against gatifloxacin and 12 other antimicrobial agents . Gatifloxacin (MIC at which 90% of the isolates are inhibited {MIC90}, </=0.03 microg/ml; 100.0% of strains inhibited at </=2 microg/ml) was the most active agent tested against H . influenzae and was similar to four comparison fluoroquinolones (MICs, </=0.03 to 2 microg/ml) against M . catarrhalis . A subset of 300 recent clinical isolates of H . influenzae were tested by using media (Haemophilus Test Medium agar and broth) and procedures recommended by the National Committee for Clinical Laboratory Standards (NCCLS) and with the E-test (AB BIODISK, Solna, Sweden) . Gatifloxacin (MIC50, 0.008 microg/ml) was slightly more active than levofloxacin, and E-test results were generally elevated by 0.5 log2 dilution step compared to reference MICs . The gatifloxacin 5-microg disk test produced zone diameters that were routinely above 30 mm for H . influenzae strains, corresponding to gatifloxacin MICs of 0.008 or 0 . 016 microg/ml . The gatifloxacin susceptibility breakpoint proposed for nonfastidious species (</=2 microg/ml; >/=18 mm) was also suggested for H . influenzae testing . No interpretive errors were observed . Quality control guidelines for H . influenzae ATCC 49247 were determined by using the NCCLS M23-T3 (1998) study design . The results from the nine-laboratory protocol suggested the following control ranges: for broth microdilution tests, 0.004 to 0.03 microg/ml; for disk diffusion testing, 33 to 41 mm . Gatifloxacin appears to be a potent anti-Haemophilus fluoroquinolone compound with in vitro testing interpretive criteria that will produce accurate results (disk diffusion, broth microdilution, and E-test). Am Fam Physician, 1999 May 1, 59(9), 2565 - 74 Combination vaccines for childhood immunization . Recommendations of the Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP) Investigation of the kinetic mechanism of cytidine 5'-monophosphate N-acetylneuraminic acid synthetase from Haemophilus ducreyi with new insights on rate-limiting steps from product inhibition analysis. Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143-0446, USAThe presence of sialic acid as a component of cell surface lipooligosaccharides or capsular polysaccharides has been shown to be correlated with the virulence of a number of Gram-negative mucosal pathogens, including several Haemophilus and Neisseria spp . As part of our efforts to evaluate the role of sialic acid in the pathobiology of these organisms, we have initiated studies of the enzymes from Haemophilus ducreyi (the infectious agent of chancroid) responsible for the activation and attachment of sialic acid to the lipooligosaccharide . In this report, we describe results of an investigation of the steady-state kinetic mechanism of the activating enzyme, cytidine 5'-monophosphate N-acetylneuraminic acid (CMP-NeuAc) synthetase . Using a combination of initial velocity, product inhibition, and dead-end inhibition studies, the reaction is shown to be freely reversible and to proceed through an ordered bi-bi kinetic mechanism in which CTP binds first and CMP-NeuAc dissociates last . In addition, a detailed analysis of the kinetic expressions for the observable constants is presented showing how the variation in apparent product inhibition constants (Kii) can be used to predict the rate-limiting step in kcat, which appears to be dissociation of CMP-NeuAc in this enzyme . To our knowledge, this relationship has not been previously recognized. FEMS Microbiol Rev, 1999 Apr, 23(2), 99 - 129 Molecular determinants of the pathogenesis of disease due to non-typable Haemophilus influenzae; Rao VK et al.; Non-typable Haemophilus influenzae is a common commensal organism in the human upper respiratory tract and an important cause of localized respiratory tract disease . The pathogenesis of disease begins with bacterial colonization of the nasopharynx, a process that involves establishment on the mucosal surface and evasion of local immune mechanisms . Under the proper circumstances, the organism spreads contiguously to the middle ear, the sinuses, or the lungs, and then stimulates a brisk inflammatory response, producing symptomatic infection . In this review, we summarize our present understanding of the molecular determinants of this sequence of events . Continued investigation of the molecular mechanism of non-typable H . influenzae pathogenicity should facilitate development of novel approaches to the treatment and prevention of H . influenzae disease. J Pediatr Surg, 1999 Apr, 34(4), 595 - 601 Reconstructive surgery in children after meningococcal purpura fulminans; Huang DB et al.; BACKGROUND/PURPOSE: Purpura fulminans (PF) is a serious, often life-threatening disease . As more children are surviving their disease, surgeons are presented with increasing numbers of multiple and complicated wounds as sequelae of PF . The purpose of this paper is to review the management of nine cases of PF, and present the reconstruction method in treating bilateral exposed elbow and knee joints . METHODS: All cases of pediatric patients with PF and treated by the division of plastic and reconstructive surgery between 1986 and 1998 were reviewed . RESULTS: Seven children (78%) had meningococcal PF, and one (11%) had PF after Haemophilus influenza septicemia . PF developed in one (11%) but with no growth in either blood or cerebrospinal fluid cultures . Five children (56%) required amputation procedures . Two children (22%) required knee disarticulation . Two patients (22%) had free myocutaneous flap transfers for bone coverage . One (11%) had PF involving the face . CONCLUSIONS: Meningococcal PF is a rare, often life-threatening disease generally of childhood . More children are surviving their diseases but with devastating sequelae . Successful reconstructive treatment outcome of these children requires a multidisciplinary team approach involving multiple specialties . The goal is to preserve function, maintain maximal length, and salvage limbs when possible . Flexibility and innovation are necessary in treating these multiple and complicated wounds. J Paediatr Child Health, 1999 Feb, 35(1), 67 - 70 Incidence of invasive pneumococcal disease in Sydney children, 1991-96; Liddle JL et al.; OBJECTIVE: Few data are available on invasive disease due to Streptococcus pneumoniae in representative Australian childhood populations . This study aimed to determine the age-specific incidence of invasive pneumococcal disease in Sydney children . METHODOLOGY: Population-based prospective study where isolates of Streptococcus pneumoniae from normally sterile sites were identified through an established laboratory surveillance network . Isolates came from children aged under 15 years living within the boundaries of Central, Eastern . Southern, Western and South-western Sydney Area Health Services from 1 July 1991 to 30 June 1996 . RESULTS: Invasive pneumococcal disease was identified in 320 children during a 5-year period, of whom 193 (60%) were under 2 years of age . The incidence per 100,000 children was 12.7 per 100,000 (95% CI: 11.4-14.2/100,000) under 15 years; 31.7 (95% CI 28.1-35.7) under 5 years, and 45.5 (95% CI 38.9-53.3) under 2 years . The incidence of pneumococcal meningitis in children aged under 2 years was 10.5 per 100,000 (95% CI: 7.4-14.5/100,000) . CONCLUSIONS: The incidence of childhood invasive pneumococcal disease in Sydney was stable during 1991-96 and comparable to rates reported from other industrialized countries . There was no evidence of any change in pneumococcal disease incidence with reduction in invasive Haemophilus influenzae type b (Hib) disease following introduction of Hib immunization. J Infect Dis, 1999 Jun, 179(6), 1423 - 32 Molecular characterization of Haemophilus ducreyi strains from Jackson, Mississippi, and New Orleans, Louisiana; Haydock AK et al.; Chancroid, a sexually transmitted disease caused by Haemophilus ducreyi, is one of the most common genital ulcer diseases in developing countries . In the United States, while less common, the disease has been associated with outbreaks in inner cities, particularly among persons who engage in sex for drugs or money . Two outbreaks of chancroid were recently studied in the United States, one in New Orleans (from 1990 to 1992) and one in Jackson, Mississippi (from 1994 to 1995) . By use of ribotyping, plasmid content, and antibiotic susceptibility, the chancroid cases in New Orleans were found to be due to a limited number of strains, consistent with a limited introduction of H . ducreyi into this community . The H . ducreyi isolates from New Orleans and Jackson had different ribotype patterns, suggesting that the two outbreaks were probably not linked. Vet Microbiol, 1999 Apr 19, 66(3), 245 - 8 Prevalence of Haemophilus parasuis serovars isolated in Spain from 1993 to 1997; Rubies X et al.; From 1993 to 1997, 327 strains of Haemophilus parasuis were isolated from spanish swine in our Diagnostic Laboratory and 174 strains (53.2%) were serotyped . Four serotypes, sv . 5 (18.4%), sv 4 (16%), sv . 2 (9.2%) and sv . 13 (8%) were the most frequently isolated and 29.3% of the studied strains were classified as non typable . The results obtained indicate that the distribution of the serotypes in Spain is very similar to that found by other researchers in Germany, Australia, Canada and alike to that found in the United States. Am J Med, 1999 Apr, 106(4), 385 - 90 Is Streptococcus pneumoniae the leading cause of pneumonia of unknown etiology? A microbiologic study of lung aspirates in consecutive patients with community-acquired pneumonia; Ruiz-Gonzalez A et al.; PURPOSE: Although a wide variety of recognized pathogens can cause community-acquired pneumonia, in many patients the etiology remains unknown after routine diagnostic workup . The aim of this study was to identify the causal agent in these patients by obtaining lung aspirates with transthoracic needle aspiration . SUBJECTS AND METHODS: During a 15-month period, all consecutive patients with community-acquired pneumonia who were eligible for transthoracic needle aspiration were enrolled in the study . In addition to conventional microbial methods (culture of blood and sputum, serologic studies), we performed cultures and genetic and antigen tests for common respiratory pathogens in lung aspirates . RESULTS: The study group consisted of 109 patients . Conventional microbial studies identified an etiology in 54 patients (50%), including Mycoplasma pneumoniae in 19 patients, Chlamydia pneumoniae in 9 patients, and Streptococcus pneumoniae in 9 patients . Among the remaining 55 patients, study of the lung aspiration provided evidence of the causal agent in 36 (65%) . In 4 additional patients with a single microbial diagnosis by conventional methods, the lung sample provided evidence of an additional microorganism . The new pathogens detected by lung aspiration were S . pneumoniae in 18 patients, Haemophilus influenzae in 6 patients, Pneumocystis carinii in 4 patients, and C . pneumoniae in 3 patients; other organisms were identified in 4 patients . CONCLUSIONS: In our study, S . pneumoniae was the leading cause of community-acquired pneumonia, accounting for 25% of all cases, including about one-third of the cases the cause of which could not be ascertained with routine diagnostic methods. Infect Immun, 1999 May, 67(5), 2649 - 52 Binding of Haemophilus ducreyi to extracellular matrix proteins; Bauer ME et al.; We developed an enzyme-linked immunosorbent assay-based assay to assess Haemophilus ducreyi binding to extracellular matrix (ECM) proteins . H . ducreyi 35000HP bound to fibronectin, laminin, and type I and III collagen but not to type IV, V, or VI collagen or elastin . Isogenic strains with mutations in ftpA or losB bound as well as the parent, suggesting that neither pili nor full-length lipooligosaccharide is required for H . ducreyi to bind to ECM proteins. Infect Immun, 1999 May, 67(5), 2590 - 601 Neutralization of macrophage inflammatory protein 2 (MIP-2) and MIP-1alpha attenuates neutrophil recruitment in the central nervous system during experimental bacterial meningitis; Diab A et al.; Chemokines are low-molecular-weight chemotactic cytokines that have been shown to play a central role in the perivascular transmigration and accumulation of specific subsets of leukocytes at sites of tissue damage . Using in situ hybridization (ISH), we investigated the mRNA induction of macrophage inflammatory protein 2 (MIP-2), MIP-1alpha, monocyte chemoattractant protein 1 (MCP-1), and RANTES . Challenge of infant rats' brains with Haemophilus influenzae type b intraperitoneally resulted in the time-dependent expression of MIP-2, MIP-1alpha, MCP-1, and RANTES, which was maximal 24 to 48 h postinoculation . Immunohistochemistry showed significant increases in neutrophils and macrophages infiltrating the meninges, the ventricular system, and the periventricular area . The kinetics of MIP-2, MIP-1alpha, MCP-1, and RANTES mRNA expression paralleled those of the recruitment of inflammatory cells and disease severity . Administration of anti-MIP-2 or anti-MIP-1alpha antibodies (Abs) resulted in significant reduction of neutrophils . Administration of anti-MCP-1 Abs significantly decreased macrophage infiltration . Combined studies of ISH and immunohistochemistry showed that MIP-2- and MIP-1alpha-positive cells were neutrophils and macrophages . MCP-1-positive cells were neutrophils, macrophages, and astrocytes . Expression of RANTES was localized predominantly to resident astrocytes and microglia . The present study indicates that blocking of MIP-2 or MIP-1alpha bioactivity in vivo results in decreased neutrophil influx . These data are also the first demonstration that the C-C chemokine MIP-1alpha is involved in neutrophil recruitment in vivo. Infect Immun, 1999 May, 67(5), 2503 - 14 Structural requirements of the major protective antibody to Haemophilus influenzae type b; Hougs L et al.; Protective antibodies to the important childhood pathogen Haemophilus influenzae type b (Hib) are directed against the capsular polysaccharide (HibCP) . Most of the antibody is encoded by a well-defined set of ("canonical") immunoglobulin genes, including the Vkappa A2 gene, and expresses an idiotypic marker (HibId-1) . In comparison to noncanonical antibodies, the canonical antibody is generally of higher avidity, shows higher levels of in vitro bactericidal activity, and is more protective in infant rats . Using site-directed mutagenesis, we here characterize canonical HibCP antibodies expressed as antigen-binding fragments (Fabs) in Escherichia coli, define amino acids involved in antigen binding and idiotype expression, and propose a three-dimensional structure for the variable domains . We found that canonical Fabs, unlike a noncanonical Fab, bound effectively to HibCP in the absence of somatic mutations . Nevertheless, pronounced mutation-based affinity maturation was demonstrated in vivo . An almost perfect correlation was found between unmutated gene segments that mediated binding in vitro and those encoding canonical HibCP antibodies in vivo . Thus, the Vkappa A2a gene could be replaced by the A2c gene but not by the highly homologous sister gene, A18b, corresponding to the demonstrated usage of A2c but not of A18b in vivo . Similarly, only Jkappa1 and Jkappa3, which predominate in the response in vivo, were able to facilitate binding in vitro . These findings suggest that the restricted immunoglobulin gene usage in HibCP antibodies reflects strict structural demands ensuring relatively high affinity prior to somatic mutations-requirements met by only a limited spectrum of immunoglobulin gene combinations. Infect Immun, 1999 May, 67(5), 2138 - 44 Immunization with recombinant transferrin binding protein B enhances clearance of nontypeable Haemophilus influenzae from the rat lung; Webb DC et al.; Nontypeable Haemophilus influenzae (NTHI) is an opportunistic pathogen, and heterogeneity in the surface-exposed immunodominant domains of NTHI proteins is thought to be associated with the failure of an infection to stimulate an immune response that is cross-protective against heterologous NTHI strains . The aim of this study was to assess the vaccine potential of a surface-exposed component of the NTHI human transferrin receptor, TbpB, and to determine if the antibody response elicited was cross-reactive with heterologous strains of NTHI . The efficacy of immunization with a recombinant form of TbpB (rTbpB) was determined by assessing the pulmonary clearance of viable bacteria 4 h after a live challenge with NTHI . There was a significant reduction in the number of viable bacteria in both the bronchoalveolar lavage fluid (34% for the 20-microgram dose and 58% for the 40-microgram dose) and lung homogenates (26% for the 20-microgram dose and 60% for the 40-microgram dose) of rats immunized with rTbpB compared to the control animals . While rTbpB-specific antibodies from immunized rats were nonspecific in the recognition of TbpB from six heterologous NTHI strains on Western blots, these antibodies differed in their ability to block transferrin binding to heterologous strains and to cross-react in bactericidal assays . If bactericidal antibodies are key indicators of the efficacy of the immune response in eliminating NTHI, this data suggests that while immunization with rTbpB stimulates protective responses against the homologous isolate, variability in the recognition of TbpB from heterologous isolates may limit the potential of rTbpB as an NTHI vaccine component. J Antimicrob Chemother, 1999 Mar, 43 Suppl A, 97 - 105 Infectious exacerbations of chronic bronchitis: diagnosis and management; Sethi S; Chronic bronchitis is an increasing cause of significant morbidity and mortality . Despite treatment, respiratory tract infection is the most common identifiable cause of death for patients with chronic obstructive pulmonary disease . Repeated infectious exacerbations may ultimately cause acute and chronic lung injury . The most common bacterial aetiologies of acute exacerbations of chronic bronchitis (AECB) include Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae . Pseudomonas aeruginosa is often a nosocomial pathogen and is becoming more prevalent in patients with severe underlying disease . Viruses are responsible for approximately one-third of acute exacerbations overall . Atypical pathogens are causative pathogens in < 10% of episodes . The diagnosis of AECB is often based on clinical impression, although suspicion of bacterial infection can be enhanced by quantitative Gram's stains from appropriately obtained sputum specimens . However, a specific microbiological diagnosis is only needed in certain specific situations . Management of AECB involves non-drug interventions (e.g . smoking cessation) and antibiotic treatment . Recommendations for antibiotic use in patients with known or highly suspected AECB are still evolving . The selection of an antibiotic for treatment of an infectious episode must consider underlying patient co-morbidities, likely pathogens, resistance issues and individual antibiotic properties . Cephalosporins, beta-lactam/beta-lactamase inhibitor combinations and macrolides are all reasonable choices . However, due to the increasing prevalence of resistance to standard antibiotics among common respiratory pathogens, and increased incidence of Pseudomonas spp., fluoroquinolones should be a first-line treatment for AECB in patients who have chronic bronchitis complicated by co-morbid illness, severe obstruction (FEV1 < 50%), old age (> 65 years) or have recurrent exacerbations . In patients who do not have these risk factors (i.e . those with simple chronic bronchitis), agents such as co-trimoxazole remain useful. J Antimicrob Chemother, 1999 Mar, 43 Suppl A, 25 - 30 Determination of the antimicrobial susceptibilities of Canadian isolates of Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis . Canadian Antimicrobial Study Group; Blondeau JM et al.; The susceptibility of Canadian isolates of three respiratory tract pathogens (Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae) to several antimicrobial agents were tested by two different methods . Beta-lactamase was produced by 68/211 (32.2%) of H . influenzae isolates and 64/75 (85.3%) of M . catarrhalis isolates . For S . pneumoniae, 19/156 (12.2%) isolates were resistant to penicillin (MIC > or = 0.12 mg/L) and two isolates had MICs of 1.5 mg/L . For some combinations of agents and organisms, different methods gave different values for the proportion of isolates susceptible . Regardless of methodology, for H . influenzae, the most active antimicrobials based on proportion of strains susceptible were ciprofloxacin (100%) and cefpodoxime (98.5-100%) . For M . catarrhalis, the most active agents were azithromycin, cefaclor, cefixime, cefpodoxime, cefuroxime, ciprofloxacin, clarithromycin and loracarbef (100% each); the least active was ampicillin . Against penicillin-sensitive and -resistant pneumococci, the activity was not significantly different for azithromycin and clarithromycin (93.4-100%) and ciprofloxacin (MIC90 2.0 and 1.5 mg/L, respectively) but was different for cefuroxime (99.3% and 31.6%, respectively), cefaclor (MIC90 0.75 and > or = 256 mg/L, respectively), cefpodoxime (MIC90 0.047 and 1.5 mg/L, respectively) and loracarbef (MIC90 0.75 and > or = 256 mg/L, respectively) . This study indicates the increasing incidence, in Canada, of beta-lactamase resistance in H . influenzae and M . catarrhalis and penicillin resistance in S . pneumoniae. Scand J Infect Dis, 1998, 30(6), 630 - 1 Polyarticular septic arthritis caused by non-encapsulated haemophilus influenzae biotype I in a rheumatic adult; Melhus A et al.; Haemophilus influenzae causes less than 1% of all septic arthritis cases in adults . Most often serotype b is responsible . Here we describe a rare case of non-encapsulated H . influenzae-induced polyarticular septic arthritis in a rheumatic patient with no other infectious focus. Arch Pediatr, 1998, 5 Suppl 1, 22s - 25s {Virus bacteria interactions in acute viral pneumonia in infancy: clinical and therapeutic consequences}; Brouard J et al.; Although signs and symptoms may become severe, most viral respiratory infections of infancy are self-limited and improvement usually occurs within several days . Patients hospitalized with viral pneumonia usually require supportive therapy, including oxygen and fluids, and eventually mechanical ventilation . Bacterial superinfection can occur, accompanied by purulent sputum production and isolation of pathogenic bacteria from sputum . Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus are the most common secondary invaders . Appropriate antibiotherapy must be administrated after cultures . There is no evidence that prophylactic antibiotherapy is of any use to prevent bacterial superinfection in viral pneumonia. Arch Pediatr, 1998, 5 Suppl 1, 14s - 17s {New spectra of resistance of the main bacteria of the respiratory tract}; Mariani-Kurkdjian P et al.; Management of acute pneumonia requires knowledge of current etiologic agents . Haemophilus influenzae and Streptococcus pneumoniae are the main responsible pathogens . Changes in epidemiology particularly occur in the susceptibility of antibiotics to S pneumoniae which is the main target of antimicrobial therapy. Arch Pediatr, 1998, 5 Suppl 1, 9s - 13s {Epidemiology of community-acquired pneumonia in children . Current data}; Marguet C et al.; Viruses, particularly syncitial respiratory virus, are the main aetiology of community-acquired lower respiratory tract infections in infants, while bacterial agents are more frequently responsible in children older than 3 years . Antimicrobial therapy must take into account the development of reduced susceptibility of penicillin to strains of Streptoccocus pneumoniae and Haemophilus influenzae with beta-lactamase, and high frequency of Mycoplasma pneumoniae and Chlamydia pneumoniae infections . Although the mortality rate has remained low in France, the morbidity appeared to increase in recent years. Arch Pediatr, 1998 Jan, 5(1), 9 - 14 {Rhinovirus infections in hospitalized children: a 3-year study}; Pierres-Surer N et al.; BACKGROUND: Rhinoviruses (RH) are responsible for acute respiratory illnesses, mainly in the upper respiratory tract . POPULATION AND METHODS: 3,152 children aged under 16 years, admitted to the Paediatrics department of the University Hospital Centre of Poitiers from January 1, 1993 to December 31, 1995 with ear, nose and throat (ENT) and/or respiratory symptoms were systematically investigated . One hundred and forty-five RH strains were isolated from nasopharyngeal secretions of 87 boys and 58 girls (mean age: 20.3 months) . Among these, 92 (63.4%) were less than 1 year of age . Bacteriological investigations were done for 29 patients when a concomitant bacterial infection was suspected . RESULTS: RH infection rate was maximum before 1 year of age (median age: 6.5 months) and decreased with age . RH were isolated throughout the 3 years, with a first peak from February to April, and a second one in autumn . The main symptoms were sibilants (27.6%) and cough (24.1%) . Sibilants were more frequently associated in children under 12 months of age (P = 0.01) . Sometimes, ophthalmologic or digestive symptoms were present . Three children with respiratory distress were transferred to the reanimation ward . In addition, a RH strain was isolated from a child who died of sudden infant death . Thirty-four children (23.4%) were co-infected by one or several viruses; the most frequently detected were the respiratory syncytial virus (41.2%) and the adenoviruses (35.3%) . Twenty-nine children were infected by two viruses and five by three . Associated bacterial infections were diagnosed in 23 children, especially conjunctivitis due to Haemophilus influenzae (21.7%) . Among these children, eight had a multiple viral infection . CONCLUSION: RH have a limited pathogenicity but can be associated with serious illnesses among infants and children. Antimicrob Agents Chemother, 1999 May, 43(5), 1291 - 3 Antimicrobial activities and postantibiotic effects of clarithromycin, 14-hydroxy-clarithromycin, and azithromycin in epithelial cell lining fluid against clinical isolates of haemophilus influenzae and Streptococcus pneumoniae; Bergman KL et al.; The antimicrobial activity of concentrations of selected macrolides found in epithelial cell lining fluid was investigated . Clarithromycin demonstrated greater potency and a significantly longer postantibiotic effect (PAE) than azithromycin against Streptococcus pneumoniae . Azithromycin displayed greater potency, faster killing, and a longer PAE than clarithromycin against Haemophilus influenzae . Drug concentrations in epithelial cell lining fluid similar to those found in tissue did not improve the synergistic potential of 14-hydroxy-clarithromycin and indicate that a maximal PAE may exist despite increasing concentrations of drug. Med Dosw Mikrobiol, 1998, 50(3-4), 223 - 8 {Level of bacterial endotoxins in Haemophilus influenzae type b vaccines conjugated with toxoids (td, Di)}; Aleksandrowicz J et al.; Quantitative evaluation of bacterial endotoxin was performed in the following vaccines: Act-Hib, Hiberix, Hib-Titer . The aim of this study was to assess the accuracy and precision of chromogenic LAL test with S-2423 substrate for this particular biopreparations and after that to determine the amounts of endotoxin as a factor of vaccine safety . Because of the lack of information concerning the presence of endotoxin in Act-Hib vaccine, we also tried to establish the limits for the presence of endotoxin in this type of vaccine . The estimated level of endotoxin was as follows: 110 EU/ml in Act-Hib, 1.64 EU/ml in Hiberix and 2.4 EU/ml in Hib-Titer . The results of this study showed that the amounts of endotoxin was dependent on the molecular size of polysaccharide PRP and on the presence of protein component . The limit of endotoxin presence in Act-Hib vaccine recommended by us is max . 150 EU/ml. Microb Pathog, 1999 May, 26(5), 249 - 62 Haemophilus influenzae localized in epithelial cell layers is shielded from antibiotics and antibody-mediated bactericidal activity; van Schilfgaarde M et al.; Nonencapsulated Haemophilus influenzae frequently persists in the lungs of chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) patients for prolonged periods of time . The bacteria are not eradicated by antibiotic treatment of the patients or by specific antibodies that are found in the sputum and sera of these patients . We investigated whether H . influenzae, when localized in lung epithelial cell layers, is shielded from antibiotics and from antibody-mediated bactericidal activity of specific antibodies . An in vitro model system consisting of lung epithelial NCI-H292 cells on permeable supports was developed to allow long term association of H . influenzae with the cells . Microscopic examination showed increasing numbers of H . influenzae bacteria between the epithelial cells up to 24 h of incubation . Coinciding with the microscopic observations the maximum number of cell-associated bacteria surviving gentamicin treatment of the cell layers was obtained after 24 h of incubation . All H . influenzae strains, and one Haemophilus parainfluenzae strain tested penetrated into the cell layer as determined by gentamicin killing . Cell-associated bacteria were shielded from the bactericidal activity of several antibiotics and from antibody-mediated bactericidal activity . After prolonged incubation in the cell system in the presence of a specific bactericidal antibody against major outer membrane protein (MOMP) P2, antigenic variation occurred due to a point mutation in the MOMP P2 gene, similar to point mutations observed in vivo . We conclude that penetration of H . influenzae between lung epithelial cells results in shielding the bacteria from killing by antibody dependent defense mechanisms and by antibiotics . Therefore, penetration of H . influenzae between epithelial cells may contribute to the persistence of this microorganism in COPD and CF patients . BMJ, 1999 May 1, 318(7192), 1169 - 72 Association between type 1 diabetes and Haemophilus influenzae type b vaccination: birth cohort study; Karvonen M et al.; OBJECTIVES: To determine the effect of Haemophilus influenzae type b vaccination and its timing on the risk of type 1 diabetes in Finnish children . DESIGN: Cumulative incidence and relative risk of type 1 diabetes was compared among three birth cohorts of Finnish children: those born during the 24 months before the H influenzae type b vaccination trial, those in the trial cohort who were vaccinated at 3 months of age and later with a booster vaccine, and those in the trial cohort who were vaccinated at 24 months of age only . The probability of type 1 diabetes was estimated using regression analysis assuming that there were no losses to 10 year follow up and no competing risks . SETTING: Finland (total population 5 million and annual birth rate 1.3%) . SUBJECTS: 128 936 children born from 1 October 1983 to 1 September 1985, and 116 352 children born from 1 October 1985 to 31 August 1987 . MAIN OUTCOME MEASURES: Probability of type 1 diabetes among children vaccinated with H influenzae type b and non-vaccinated children . RESULTS: No statistically significant difference was found at any time during the 10 year follow up in the risk of type 1 diabetes between the children born before the vaccination period and those vaccinated at the age of 24 months only (relative risk 1.01) . The difference in the risk between the cohort vaccinated first at the age of 3 months and the cohort vaccinated at the age of 24 months only was not statistically significant either (1.06) . CONCLUSION: It is unlikely that H influenzae type b vaccination or its timing cause type 1 diabetes in children. Mayo Clin Proc, 1999 Apr, 74(4), 420 - 34 Carbapenems and monobactams: imipenem, meropenem, and aztreonam; Hellinger WC et al.; Imipenem and meropenem, members of the carbapenem class of beta-lactam antibiotics, are among the most broadly active antibiotics available for systemic use in humans . They are active against streptococci, methicillin-sensitive staphylococci, Neisseria, Haemophilus, anaerobes, and the common aerobic gram-negative nosocomial pathogens including Pseudomonas . Resistance to imipenem and meropenem may emerge during treatment of P . aeruginosa infections, as has occurred with other beta-lactam agents; Stenotrophomonas maltophilia is typically resistant to both imipenem and meropenem . Like the penicillins, the carbapenems have inhibitory activity against enterococci . In general, the in vitro activity of imipenem against aerobic gram-positive cocci is somewhat greater than that of meropenem, whereas the in vitro activity of meropenem against aerobic gram-negative bacilli is somewhat greater than that of imipenem . Daily dosages may range from 0.5 to 1 g every 6 to 8 hours in patients with normal renal function; the daily dose of meropenem, however, can be safely increased to 6 g . Infusion-related nausea and vomiting, as well as seizures, which have been the main toxic effects of imipenem, occur no more frequently during treatment with meropenem than during treatment with other beta-lactam antibiotics . The carbapenems should be considered for treatment of mixed bacterial infections and aerobic gram-negative bacteria that are not susceptible to other beta-lactam agents . Indiscriminate use of these drugs will promote resistance to them . Aztreonam, the first marketed monobactam, has activity against most aerobic gram-negative bacilli including P . aeruginosa . The drug is not nephrotoxic, is weakly immunogenic, and has not been associated with disorders of coagulation . Aztreonam may be administered intramuscularly or intravenously; the primary route of elimination is urinary excretion . In patients with normal renal function, the recommended dosing interval is every 8 hours . Patients with renal impairment require dosage adjustment . Aztreonam is used primarily as an alternative to aminoglycosides and for the treatment of aerobic gram-negative infections . It is often used in combination therapy for mixed aerobic and anaerobic infections . Approved indications for its use include infections of the urinary tract or lower respiratory tract, intra-abdominal and gynecologic infections, septicemia, and cutaneous infections caused by susceptible organisms . Concurrent initial therapy with other antimicrobial agents is recommended before the causative organism has been determined in patients who are seriously ill or at risk for gram-positive or anaerobic infection. Int J Antimicrob Agents, 1999 Feb, 11(2), 139 - 43 The bactericidal activity of levofloxacin against ampicillin-resistant and ampicillin-susceptible Haemophilus influenzae in comparison with ofloxacin, ciprofloxacin and sparfloxacin; Dabernat H; The bactericidal activity of levofloxacin against four Haemophilus influenzae clinical isolates (two ampicillin-resistant and two susceptible) was compared with that of ofloxacin, ciprofloxacin and sparfloxacin at concentrations simulating the peak serum concentrations obtained with the recommended oral doses . Bactericidal activity was assessed using time-kill curves and minimum kill-time values . Both concentrations of levofloxacin rapidly killed all the study strains, with mean kill times of 4 h and no viable bacteria remaining after 18-h exposure . The bactericidal activities of levofloxacin, ofloxacin and sparfloxacin were similar . The minimum kill-times for both concentrations of ciprofloxacin were 28-35% longer than those of levofloxacin . These results support the use of levofloxacin for H . influenzae infections, including ampicillin-resistant strains. Jpn J Antibiot, 1999 Feb, 52(2), 162 - 71 {Causative organisms of acute otitis media and acute sinusitis in children and their susceptibility of oral beta-lactam antibiotics}; Takenaka M et al.; The clinical efficacy of cefditoren pivoxil (CDTR-PI) was evaluated for 43 pediatric patients with acute otitis media or acute sinusitis . The causative organisms were identified and their susceptibilities to 6 oral beta-lactam antibiotics were measured; ampicillin (ABPC), cefaclor (CCL), cefdinir (CFDN), cefditoren pivoxil (CDTR-PI), cefteram pivoxil (CFTM-PI) and cefpodoxime proxetil (CPDX-PR) . The ages of 43 patients were distributed from 4 months to 10 years and 7 months, and especially children under 4 years accounted for 72% (31 cases) . In 22 cases (51%), Haemophilus influenzae or Streptococcus pneumoniae were identified as the pathogens, but in 18 cases, no causative organisms were defined . Treatment by CDTR-PI was successful in 12 cases out of 15 evaluable cases in which H . influenzae or S . pneumoniae were identified as the main causative organisms . From the susceptibility testing of them, some strains of H . influenzae were found to be ABPC-resistant and some strains of S . pneumoniae were benzylpenicillin (PCG)-resistant . To support above clinical evaluation of CDTR-PI, susceptibility testings on clinically isolated H . influenzae (81 strains) and S . pneumoniae (79 strains) were performed using above mentioned 6 oral beta-lactam antibiotics . The MIC80s against H . influenzae were; CDTR-PI 0.06 microgram/ml, CCL 2 micrograms/ml, CPDX-PR 0.125 microgram/ml, CFTM-PI 0.03 microgram/ml, CFDN 1 microgram/ml and ABPC 1 microgram/ml . Those against S . pneumoniae were; CDTR-PI 0.5 microgram/ml, CCL > 4 micrograms/ml, CPDX-PR 2 micrograms/ml, CFTM-PI 1 microgram/ml, CFDN 2 micrograms/ml and ABPC 1 microgram/ml . From those results, it was concluded that CDTR-PI or CFTM-PI may be preferable for the treatment of acute otitis media and acute sinusitis in children. FEMS Microbiol Lett, 1999 Apr 1, 173(1), 95 - 102 Variable numbers of tandem repeat loci in genetically homogeneous Haemophilus influenzae strains alter during persistent colonisation of cystic fibrosis patients; Renders N et al.; Serial sputum isolates of Haemophilus influenzae (n = 69) were obtained from eight patients suffering from cystic fibrosis . For two of these patients all strains were analysed for polymorphism in the major outer membrane protein profile . For all patients the strains were genetically characterised by random amplification of polymorphic DNA analysis . All strains were included in a survey for polymorphism in regions containing moieties of repetitive DNA as well . A single locus containing trinucleotide repeat units, three loci harbouring tetranucleotides, one region comprising pentanucleotide units and two hexanucleotide repeat unit-containing loci were analysed for repeat number variability . Most of the regions were previously shown to be directly adjacent to or even within virulence genes . All regions behaved as genuine variable number of tandem repeat loci in the sense that genetic polymorphism based on the presence of varying numbers of repeat units could be demonstrated among different strains . Interestingly, several of the repeats showed variation in the absence of the variability as assessed by major outer membrane protein or random amplification of polymorphic DNA analysis . These observations indicate that the repeat loci may vary independently from major chromosomal polymorphism . Consequently, H . influenzae appears to modify its virulence gene regions of the chromosome during persistent colonisation of the lung in cystic fibrosis patients. Microbiology, 1999 Apr, 145 ( Pt 4), 905 - 14 Characterization of hgpA, a gene encoding a haemoglobin/haemoglobin-haptoglobin-binding protein of Haemophilus influenzae; Jin H et al.; Haemophilus haemoglobin-haptoglobin complex and utilizes either as a sole source of haem . Previously, a DNA fragment was cloned from H . influenzae that encodes an approximately 120 kDa protein (HgpA) expressing haemoglobin-binding activity in Escherichia coli . Partial sequence analysis revealed significant homology of HgpA with other bacterial haem- and iron-utilization proteins, and a length of CCAA repeating units immediately following the nucleotide sequence encoding the putative leader peptide . In the present study, the complete nucleotide sequence of the cloned DNA fragment was determined and the sequence was analysed . In addition to homology with other haem- and iron-utilization proteins, seven regions typical of TonB-dependent proteins were identified . The transcript of hgpA was determined to be monocistronic by RT-PCR . PCR performed with different colonies of a single H . influenzae strain at one CCAA-repeat-containing locus indicated varying lengths of CCAA repeats, suggesting that haemoglobin and haemoglobin-haptoglobin binding in H . influenzae is regulated by strand slippage across CCAA repeats, as well as by haem repression . E . coli containing cloned hgpA bound both haemoglobin and the haemoglobin-haptoglobin complex . A deletion/insertion mutation of hgpA was constructed in H . influenzae strain H1689 . Mutation of hgpA did not affect the ability of H . influenzae either to bind or to utilize haemoglobin or haemoglobin-haptoglobin following growth in haem-deplete media . Affinity purification of haemoglobin-binding proteins from the mutant strain revealed loss of the 120 kDa protein and an increased amount of a 115 kDa protein, suggesting that at least one additional haemoglobin-binding protein exists. Scand J Immunol, 1999 Apr, 49(4), 411 - 6 Induction of phagocyte-stimulating cytokines by in vitro stimulation of human peripheral blood mononuclear cells with Haemophilus influenzae; Arva E et al.; The aim of this study was to analyse the in vitro response of human peripheral blood mononuclear cells to stimulation with killed Haemophilus influenzae strains of different capsular types, isolation sites and from cases with different forms of infections . The mean stimulatory index using 10(6) bacteria/well was 10, and 80 when 10(8) bacteria/well were used for stimulation . The mean+/-SD level was 13+/-4 ng/ml for interleukin (IL)-1beta, 128+/-73 ng/ml for IL-6, 203+/-122 ng/ml for IL-8, 3160+/-1220 pg/ml for IL-10, 29+/-40 pg/ml for IL-12, 2800+/-1790 pg/ml for tumour necrosis factor (TNF)-alpha and 4+/-7 ng/ml for interferon (IFN)-gamma, when stimulating cells with the lower dose of 10(6) bacteria/well . Using the higher bacterial dose, the levels of IL-1beta, TNF-alpha and IL-12 remained similar, whereas the IL-6, IL-8 and IL-10 levels were significantly lower, and IFN-gamma levels were significantly higher . Strains isolated from the bronchial tree induced significantly higher levels of IFN-gamma and significantly lower levels of IL-6, IL-8 and IL-10 than strains from other isolation sites . In conclusion, H . influenzae generated phagocyte-activating cytokines and an IL-10/IL-12 ratio that was 1090 times that described previously for Streptococcus pneumoniae. Monaldi Arch Chest Dis, 1999 Feb, 54(1), 43 - 8 Infectious exacerbations of chronic bronchitis . ORIONE Board; Donner CF; Approximately 50% of chronic bronchitis exacerbations are caused by bacteria and 25-50% by viruses . Streptococcus pneumoniae and Haemophilus influenzae are traditionally considered leading pathogens . In Italy, S . pneumoniae and H . influenzae resistance to beta-lactams is low but resistance to macrolides is more widespread . Pathogenic bacteria are isolated in the airways of most chronic bronchitis patients, impairing host respiratory defences, further predisposing towards infection and, thus, establishing a vicious circle, fuelled by damage due to cigarette smoking . The diagnosis of an exacerbation is essentially clinical . Lung function testing may show no modification, or indicate worsening airway obstruction . Blood gas analysis is performed in severe cases . The utility of culture is lessened by evidence of airway bacterial contamination in clinically stable periods . Quantitative thresholds have been identified over and above which bacterial exacerbation is considered probable . General preventative measures include the adoption of hygiene-behavioural standards . Antibiotic prophylaxis is not advisable . Prophylaxis by means of vaccination is indicated against influenza . Vaccination against S . pneumoniae is available but is seldom employed . The principal form of treatment is antibiotic therapy, but there is an ongoing debate regarding the objective criteria for its use . A recent meta-analysis showed a small but statistically significant difference in favour of antibiotic treatment . The antibiotic cost-benefit ratio is favourable in patients with severe functional impairment . Oral administration is to be preferred as more practical and less costly for equal efficacy . In selecting an antibiotic, pharmacokinetic considerations (bioavailability, tissue diffusion, half-life) must be kept in mind . Prescription should be oriented towards drugs active against the most commonly occurring pathogens . In more severe cases coverage against Gram-negative bacteria is considered . Complementary medical treatment includes bronchodilators corticosteroids, diuretics, and oxygen therapy . Chest physiotherapy may be beneficial . Ventilatory support treatment may be necessary, noninvasive ventilatory assistance being preferable early in the course of the acute episode . In a high number of cases endotracheal intubation may be avoided . Most exacerbations may be treated on an outpatient basis, but in some cases admission to hospital is indicated. Avian Dis, 1999 Jan-Mar, 43(1), 75 - 82 A monoclonal antibody-blocking enzyme-linked immunosorbent assay for the detection of serovar-specific antibodies to Haemophilus paragallinarum; Zhang P et al.; Two monoclonal antibody-blocking enzyme-linked immunosorbent assays (B-ELISAs) were developed to detect serovar-specific antibodies to Haemophilus paragallinarum . One assay detected antibodies against serovar A and the other antibodies against serovar C . The assays were evaluated with sera derived from disease-free chickens as well as chickens experimentally immunized and/or challenged with H . paragallinarum strains 0083 (serovar A), Modesto (serovar C), or HP31 (serovar C) . When tested with 440 negative sera (170 from a specific-pathogen-free and 30 from each of nine commercial layer flocks), both tests gave only a single false-positive reaction . The use of the B-ELISAs with the experimentally produced sera showed the assays to be serovar specific . With the exception of one serum, the serovar A B-ELISA detected antibodies only in the chickens vaccinated with 0083 . Similarly, with the exception of one serum, the serovar C B-ELISA detected antibodies only in those chickens vaccinated with Modesto or those chickens challenged with HP31 . Overall, the serovar A B-ELISA had a specificity of 99.7% and a sensitivity of 78.7%, whereas the serovar C B-ELISA had a specificity of 99.8% and a sensitivity of 64.7%. Gene, 1999 Apr 16, 230(2), 287 - 93 Fragmentation heterogeneity of 23S ribosomal RNA in Haemophilus species; Song XM et al.; The fragmentation of 23S rRNA of 23 Haemophilus influenzae strains and eight strains belonging to other Haemophilus species was investigated . Instead of intact molecules, the 23S rRNA molecules were found to be cleaved into two to five smaller conserved fragments in most strains examined, especially in H . influenzae type b (5/6) and nontypeable strains (5/5) . One or two conserved potential cleavage sites were identified by PCR analysis of the strains showing a fragmented 23S rRNA pattern . The relevant nucleotide sequences were determined and compared to H . influenzae Rd, which contains intact 23S rRNA molecules . An identical 112bp long intervening sequence (IVS) at position 542 and a conserved 121-123bp IVS sequence at position 1171 were found in two H . influenzae type b strains and one nontypeable strain . Among the strains with fragmented 23S rRNA, nearly half showed a heterogeneous cleavage pattern due to the dispersion of IVSs among different 23S rRNA operons . The localization of the conserved H . influenzae IVSs coincided well with the extensively studied IVSs among other bacteria, but differed in nucleotide sequence from any other reported IVSs . Therefore, the IVSs of Haemophilus 23S rRNA may originate from a common source that is independent of other bacteria. Neurology, 1999 Apr 12, 52(6), 1282 - 4 Haemophilus influenzae has a GM1 ganglioside-like structure and elicits Guillain-Barré syndrome; Mori M et al.; The authors report a patient with an axonal Guillain-Barre syndrome (acute motor axonal neuropathy) associated with anti-GM1 antibody after Haemophilus influenzae infection . The result of ELISA inhibition studies and cytochemical staining with cholera toxin suggest the presence of a GM1-like structure on the surface of H . influenzae isolated from the patient . A particular strain of H . influenzae may have a GM1-like structure and may elicit an axonal Guillain-Barre syndrome. Afr J Reprod Health, 1997 Sep, 1(2), 26 - 35 Sexually transmitted diseases and risk of HIV infection in men attending a sexually transmitted diseases clinic in Dakar, Senegal; Thior I et al.; This cross-sectional study was carried out among male outpatients with symptoms of STDs at the STD reference centre at the Institute of Social Hygiene (IHS), Dakar, Senegal, from March 1989 through May 1991 . This study was used to determine the prevalence of STDs and HIV among male patients attending an STD clinic and to identify their socio-demographic characteristics and risk factors . A total of 975 patients were enrolled in the study . The most common syndromes were urethritis (76%) and genital ulcers (22%) . Considering single infections, the major STD agents were Neisseria gonorrheae (N.gonorrheae, 30%), Chlamydia trachomatis (C.trachomatis, 15%), Treponema pallidum (T.pallidum, 12%), and Haemophilus ducreyi (H.ducreyi, 7%) . HIV prevalence was 2.6 percent (25/975) . After multivariate analysis, the risk factors associated with HIV infection were a history of sex with prostitutes (odds ratio {OR} = 8.6, 95% confidence interval {CI} = 2.0-37.8), unprotected sexual contact (OR = 5.6, 95% CI = 1.2-25.0), a history of urethritis (OR = 3.4, 95% CI = 1.3-8.9), current STDs due to H.ducreyi or T.pallidum (OR = 6.1, 95% CI = 2-18.8), and mixed STD infection (OR = 5.3, 95% CI = 1.3-21.8) . HIV prevalence was quite low in this population compared to similar studies of STD patients from other sub-Saharan African countries . Neisseria gonorrheae and Chlamydia trachomatis were the leading causes of STDs . A history of risky sexual behaviour, previous STDs, current genital ulcers, and mixed STD infections were associated with HIV infection . Further studies are necessary to determine changes in the relationship of STDs and HIV infection in this population. Diagn Microbiol Infect Dis, 1999 Apr, 33(4), 275 - 82 Comparative in vitro evaluation of dirithromycin tested against recent clinical isolates of Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae, including effects of medium supplements and test conditions on MIC results; Biedenbach DJ et al.; The use of macrolides for treatment of respiratory complaints has been complicated by susceptibility test conditions that adversely effect the in vitro test results and perceived potencies of these compounds . Dirithromycin was studied as to its in vitro activity compared to other macrolides as well as the effects that environmental incubation variations and inoculum concentrations may have on susceptibility results . Dirithromycin was less active than other macrolides tested (azithromycin clarithromycin, erythromycin) against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis with MIC90 values of 16, 32, and 1 microgram/ml, respectively; an activity that was most similar to roxithromycin . This reduced activity may be compensated by the superior pharmacokinetic properties that dirithromycin possesses compared to other members in its class . Method variation studies show that incubation in CO2 environments increase the MIC values for all macrolide compounds and dirithromycin was most effected by pH changes in three in vitro methods tested (Etest {AB BIODISK, Solna, Sweden} broth microdilution, and disk diffusion) . Variations in inoculum concentration had minimal effect on dirithromycin potency . In addition the variability (lack of reproducibility) of the test results with dirithromycin were not significant . Dirithromycin is an alternative therapeutic choice among macrolide compounds for treatment of community-acquired respiratory infections caused by various streptococci, Legionella pneumophilia, Mycoplasma pneumoniae and M . catarrhalis, and also possesses a modest in vitro potency versus H . influenzae coupled with excellent pharmacokinetic properties . In vitro tests with dirithromycin will continue to be problematic for H . influenzae because of the adverse effects of recommended CO2 incubation for some standardized methods or commercial products (Etest). Pharmacotherapy, 1999 Apr, 19(4), 404 - 15 Review and comparison of advanced-generation macrolides clarithromycin and dirithromycin; McConnell SA et al.; We reviewed English-language clinical studies, abstracts, and review articles identified from MEDLINE searches from January 1966-August 1998, and bibliographies of identified articles to compare advanced-generation macrolides dirithromycin and clarithromycin and their use for respiratory tract infections . Both agents have superior adverse effect profiles compared with erythromycin, the original macrolide . Both have broad antibacterial coverage, but clarithromycin usually has a lower MIC90 to susceptible organisms than dirithromycin; for most isolates this difference is not clinically significant . Clarithromycin has better in vitro coverage of Haemophilus influenzae, but this activity varies with formation of its bioactive metabolite, 14-hydroxyclarithromycin . Neither agent is ideal for H . influenzae eradication . The agents differ markedly in terms of pharmacokinetics, pharmacodynamics, metabolism, and cost, and thus with respect to drug interaction profiles and dosages . Dirithromycin's drug interaction profile is markedly better than clarithromycin's . Clarithromycin is dosed twice/day; dirithromycin's pharmacokinetics allow once/day dosing . Dirithromycin is less expensive with regard to both cost/day and cost/treatment regimen . Clarithromycin has been studied and approved for administration to children . In adults with respiratory tract infections who are receiving drugs that would interact with clarithromycin, and in those with renal dysfunction with or without coexisting hepatic dysfunction, dirithromycin appears to be superior in terms of safety and equivalent to clarithromycin in terms of efficacy. Res Microbiol, 1999 Mar, 150(2), 83 - 93 Molecular nature of RAPD markers from Haemophilus influenzae Rd genome; Mori E et al.; Despite the widespread application of the random amplified polymorphic DNA (RAPD) technique, there is no experimental evidence of the molecular mechanism of random amplification starting from a complex template . To investigate this mechanism, we cloned and sequenced 23 selected RAPD bands amplified from Haemophilus influenzae Rd genomic DNA using eight decamer primers different in GC content and/or nucleotide sequence . As the whole genome sequence of H . influenzae Rd has been reported, the exact nucleotide sequence of each primer-template annealing site was identified . Results showed that, on an average, a homology of eight base pairs was involved in priming events and that the number of nonhomologous base pairings declined exponentially from the 5' end of the primer to its 3' end . The interaction between the primer and the template DNA was stabilized by the formation of secondary structures, and a perfect match of the 3' terminal region of the primer was not necessary for successful amplification . The complexity of the annealing process suggested that, in the studied reaction conditions, many primer-template annealing sites were extended in the first cycles and that differences in the efficiency of priming and replication processes led to amplification of RAPD fragments . Moreover, the distribution of the amplified regions on the H . influenzae chromosome was analyzed. J Chemother, 1999 Feb, 11 Suppl 1, 51 - 5 Basing empiric treatment choices for respiratory tract infection on the results of the Alexander Project; Garau J; For respiratory tract infection (RTI), antibiotics should have proven clinical efficacy against the major pathogens involved-Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis . As the pattern of resistance to antimicrobials changes, the clinical effectiveness of these agents should be reviewed . However, clinical trials are time consuming and costly, and alternative ways of predicting clinical efficacy using susceptibility data have been investigated . Pharmacodynamic breakpoints have been suggested as providing the link between susceptibility data and clinical effectiveness and this is supported by emerging clinical evidence . Thus, using the data collected in the Alexander Project, guidelines for the treatment of RTI can be developed which reflect the local resistance profile and maximize the chances of clinical success. J Chemother, 1999 Feb, 11 Suppl 1, 44 - 50 Resistance patterns of Haemophilus influenzae; Acar JF; Haemophilus influenzae is an important respiratory tract pathogen, and the prevalence of strains resistant to the antibiotics used to treat it has increased since the 1970s . Data on H . influenzae have been gathered in the Alexander Project, an ongoing, international surveillance study . They reveal that beta-lactamase production is the primary mechanism for H . influenzae resistance and that the resistance has a wide geographical variation, reaching critical levels in some countries . Unlike many techniques used in the past, Alexander Project methods provide accurate, reproducible susceptibility data, allowing the comparison of resistance prevalence over time and between areas . Traditional antimicrobial breakpoints are being superseded by more accurate and clinically relevant methods of predicting drug efficacy, such as time above the MIC, AUC:MIC ratios and pharmacodynamic breakpoints . Continued surveillance for resistance and susceptibility testing of H . influenzae is vital to maximize the benefits of antimicrobial therapy and to contain the spread of infection. J Chemother, 1999 Feb, 11 Suppl 1, 5 - 21 Trends in the antimicrobial susceptibility of bacterial respiratory tract pathogens--findings of the Alexander Project 1992-1996; Felmingham D et al.; The Alexander Project is an ongoing, multicenter surveillance study of the antimicrobial susceptibility of community-acquired lower respiratory tract bacterial pathogens with testing undertaken in a central laboratory . During the period 1992-1995, isolates were collected from geographically separate centers in countries of the EU and various states in the USA . In 1996, the project was extended to centers in Mexico, Brazil, Saudi Arabia, South Africa, Hong Kong and other European countries not previously included . Within Europe, France and Spain are established as centers with a high prevalence of both penicillin-intermediate (MIC 0.12-1 mg/l) and resistant (MIC > or = 2 mg/l) strains of Streptococcus pneumoniae, with combined resistance rates in excess of 40% in Toulouse and Barcelona in 1996 . Combined rates of intermediate and resistant strains in excess of 10% were found in 1996, the first year of sampling, in Belgium, Switzerland, the Slovak Republic and Hungary . Penicillin resistance has evolved in the USA during the period of study, with rates for combined pneumococcal isolates increasing from 5.6% in 1992 to 16.4% in 1996 . Of the new, non-European centers joining the project in 1996, Mexico (intermediate 31.4%, resistant 15.7%) and, in particular, Hong Kong (intermediate 9.1%, resistant 50%) are centers with a high prevalence of penicillin resistance . Macrolide resistance has increased generally among pneumococcal isolates examined during the study period, both in penicillin-susceptible and resistant isolates, and was evident in 16.5% of the 2160 isolates collected during 1996 . In four centers (London, UK; Genoa, Italy; Pokfulum, Hong Kong; Leuven, Belgium), macrolide resistance rates exceeded those of combined penicillin-intermediate and resistant strains; in 12/19 centers (63.2%) macrolide resistance was more prevalent than penicillin resistance . In 1996, macrolide resistance was found in excess of 10% of isolates in Poland, Hungary, London, UK, combined USA isolates, the Slovak Republic, Barcelona, Spain, Genoa, Italy, Mexico, Toulouse, France and Pokfulum, Hong Kong . beta-lactamase production was the principal mechanism of resistance found among isolates of Haemophilus influenzae, with rates in 1996 of around 20% or more in France, Belgium and Spain, and in excess of 10% in the UK and the Czech Republic . In the same year in non-European centers, Mexico (25%), Saudi Arabia (27.9%), Hong Kong (37.1%) and the USA (30.4% of combined isolates) had a high prevalence of beta-lactamase production . Isolates of beta-lactamase-negative, ampicillin-resistant H . influenzae were generally very uncommon, with only Barcelona, Spain consistently associated with rates in excess of 1% . beta-lactamase production in Moraxella catarrhalis was observed in over 90% of isolates tested in 1996. Int J Pediatr Otorhinolaryngol, 1999 Jan 25, 47(1), 49 - 56 In vitro inhibition of S . pneumoniae, nontypable H . influenzae and M . catharralis by alpha-hemolytic streptococci from healthy children; Tano K et al.; The present study aimed to investigate the inhibitory activity of the normal epipharyngeal flora against the three most common acute otitis media (AOM) pathogens in healthy children, and to study if the inhibitory activity differs between alpha-hemolytic streptococci (AHS) sampled from the tubal orifice and from those sampled from the adenoid . A total number of ten isolates of AHS were collected from the tubal orifice and the adenoid, respectively, in ten children undergoing adenoidectomy or tonsillectomy . None of the children had a history of otitis media, neither secretory otitis media (SOM) nor AOM . The method used to test the bacterial interference in vitro was a modified agar overlay method . The results showed that the AHS from nasopharynx were able to inhibit the majority of the S . pneumoniae, nontypable Haemophilus influenzae and Moraxella catharralis isolates tested . The AHS isolates from the tubal orifice inhibited growth of 93% of S . pneumoniae, 79% of H . influenzae and 84% of M . catharralis isolates . The corresponding figures among isolates from the adenoid were 76, 48 and 62% . This difference in the inhibitory capacity between the AHS isolates collected from the adenoid, compared with the AHS collected from the tubal orifice, is statistically significant (P<0.01) and implies that it is important to know the exact sampling locality before conclusions are made concerning the significance of bacterial interference in the upper airways. Eur J Pediatr, 1999 Apr, 158(4), 329 - 36 Adverse effects and sero-responses to an acellular pertussis/diphtheria/tetanus vaccine when combined with Haemophilus influenzae type b vaccine in an accelerated schedule; Bell F et al.; Acellular pertussis vaccines provide protection against pertussis with few adverse effects . Differences in the reactogenicity and immunogenicity of available pertussis vaccines may be influenced by the immunisation schedule employed . We assessed responses to an acellular pertussis, diphtheria, tetanus vaccine mixed with Haemophilus influenzae type b (Hib) vaccine, (PRP-T) given at age 2, 3 and 4 months . Parents kept a symptom diary for 3 days after each immunisation . Antibodies to diphtheria, tetanus, pertussis toxin and filamentous haemagglutinin were measured by enzyme immunoassay at 2 and 5 months . Results were compared with historical controls who received a combination whole-cell pertussis, diphtheria, tetanus/PRP-T vaccine in the same schedule . A total of 262 infants were recruited, of whom 251 were fully evaluated after three doses of vaccine . Systemic and most local reactions were less frequent following the acellular combination . Fever > or = 38 degrees C was reported after only 0.6% of doses . Redness or swelling > or = 2.5 cm were unusual after the first two doses (2-5%), but rates rose to 13% after the third dose . Antibody responses to diphtheria and tetanus toxoids were lower, while those to pertussis antigens were higher, more uniform and less attenuated by pre-immunisation antibody than in infants who received the whole-cell combination . All infants achieved protective antibody titres of at least 0.1 IU/ml for diphtheria and 0.01 IU/ml for tetanus . CONCLUSION: The acellular combination vaccine was immunogenic for diphtheria, tetanus and pertussis components and was associated with low rates of fever following immunisation. J Clin Microbiol, 1999 May, 37(5), 1524 - 31 Pulsed-field gel electrophoresis used to investigate genetic diversity of Haemophilus influenzae type b isolates in Australia shows differences between Aboriginal and non-Aboriginal isolates; Moor PE et al.; We used pulsed-field gel electrophoresis to study the epidemiology and population structure of Haemophilus influenzae type b . DNAs from 187 isolates recovered between 1985 and 1993 from Aboriginal children (n = 76), non-Aboriginal children (n = 106), and non-Aboriginal adults (n = 5) in urban and rural regions across Australia were digested with the SmaI restriction endonuclease . Patterns of 13 to 17 well-resolved fragments (size range, approximately 8 to 500 kb) defining 67 restriction fragment length polymorphism (RFLP) types were found . Two types predominated . One type (n = 37) accounted for 35 (46%) of the isolates from Aboriginals and 2 (2%) of the isolates from non-Aboriginals, and the other type (n = 41) accounted for 2 (3%) of the isolates from Aboriginals and 39 (35%) of the isolates from non-Aboriginals . Clustering revealed seven groups at a genetic distance of approximately 50% similarity in a tree-like dendrogram . They included two highly divergent groups representing 50 (66%) isolates from Aboriginals and 6 (5%) isolates from non-Aboriginals and another genetically distinct group representing 7 (9%) isolates from Aboriginals and 81 (73%) isolates from non-Aboriginals . The results showed a heterogeneous clonal population structure, with the isolates of two types accounting for 42% of the sample . There was no association between RFLP type and the diagnosis of meningitis or epiglottitis, age, sex, date of collection, or geographic location, but there was a strong association between the origin of isolates from Aboriginal children and RFLP type F2a and the origin of isolates from non-Aboriginal children and RFLP type A8b . The methodology discriminated well among the isolates (D = 0.91) and will be useful for the monitoring of postvaccine isolates of H . influenzae type b. Can Respir J, 1999 Jan-Feb, 6 Suppl A, 35A - 9A Levofloxacin in the treatment of community acquired pneumonia; File TM Jr; Levofloxacin is the first fluoroquinolone with enhanced activity against Streptococcus pneumoniae to be released in Canada . In vitro, it is active against more than 99% of isolates of S pneumoniae, even those resistant to penicillin . It is also active against respiratory pathogens such as Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella species . When given orally, bioavailability is greater than 99%, and the drug is highly concentrated in lung tissue and macrophages . Drug levels are compatible with once-daily dosing . In a large clinical trial, levofloxacin has shown clinical and microbiological superiority compared with ceftriaxone/cefuroxime . The characteristics of levofloxacin - high oral bioavailability, long duration of effect, activity against key respiratory pathogens and high tolerability - suggest that it will be a useful drug in the treatment of community acquired pneumonia. AIDS, 1999 Apr 1, 13(5), 607 - 14 Cofactors for the acquisition of HIV-1 among heterosexual men: prospective cohort study of trucking company workers in Kenya; Rakwar J et al.; OBJECTIVE: To determine the prevalence, incidence, and correlates of HIV-1 infection in a cohort of east African trucking company employees . METHODS: HIV-1-seronegative trucking company employees were enrolled in a prospective cohort study and evaluated at 3 monthly intervals for HIV-1 seroconversion, sexually transmitted diseases, and sexual behavior . RESULTS: The baseline seroprevalence of HIV-1 among 1500 trucking company employees was 17.8% . Among 752 HIV-1-seronegative men who were followed, the HIV-1 annual seroincidence was 3.1% . In univariate analysis, HIV-1 acquisition was associated with age under 25 years, 10 years or less of sexual activity, occupation as a driver/driver's assistant, occupational travel for more than 14 days per month, religion other than Christian or Muslim, uncircumcised status, sex with a prostitute, sex with a girlfriend/casual partner, extramarital sex, and enrollment seropositivity to Treponema pallidum, Haemophilus ducreyi, and Herpes simplex virus type 2 (all P values < or = 0.05) . Using multivariate analysis, HIV-1 acquisition was independently associated with 10 years or less of sexual activity (hazard rate ratio (HRR) 2.0, 95% confidence interval (CI) 1.0-4.3), occupation as a driver/driver's assistant (HRR 3.9, 95% CI 1.7-9.0), religion other than Christian or Muslim (HRR 6.1, 95% CI 1.4-25.7), uncircumcised status (HRR 2.3, 95% CI 1.0-5.0), and unprotected sex with a prostitute (HRR 2.8, 95% CI 1.1-7.0) . CONCLUSIONS: Trucking company employees had a high HIV-1 seroprevalence rate at enrollment and a high HIV-1 seroincidence during follow-up . Risk factors for HIV-1 seroconversion included years of sexual activity, occupation, religion, uncircumcised status, and unprotected sex with a prostitute . This population is an appropriate target for HIV-1 prevention trials and behavioral interventions. Am J Otolaryngol, 1999 Mar-Apr, 20(2), 85 - 90 Clinical, bacteriological, and histological study of adenoids in children; Suzuki M et al.; PURPOSE: The adenoid has long been recognized as an important factor in the pathogenesis of otitis media with effusion (OME) . However, there is still considerable debate concerning how the condition of the adenoid tissue is involved in the cause of OME . The purpose of this study is to investigate whether the adenoid is an active agent of OME . PATIENTS AND METHODS: One hundred forty-six patients aged from 3 to 6 years who underwent adenoidectomy at Oita Medical University (Japan) were retrospectively compared with patients with and without OME regarding macroscopic size of the adenoid, adenoidal-nasopharyngeal ratio (AN ratio), incidence of sinusitis and nasal allergy, bacteriological examination of adenoid tissues, reticular formation of the epithelium, and the percent of ciliated epithelium . RESULTS: There was no significant difference in the size of adenoids . Haemophilus influenzae (HI) was cultured more frequently in adenoid specimens from patients with OME . A tendency toward increased stratified squamous epithelium and decreased ciliated epithelium was apparent in patients with OME . Reticular epithelium extension was greater in patients with than without OME . CONCLUSION: Adenoid inflammation is implicated in the pathogenesis of OME and the adenoids have an important role in the cause of OME by being a reservoir for HI. Can Respir J, 1999 Jan-Feb, 6 Suppl A, 40A - 5A Management of acute exacerbation of chronic bronchitis; Grossman RF; In chronic bronchitis, a common respiratory illness marked by chronic productive cough and caused largely by cigarette smoking, bacterial exacerbations are thought to be a common cause of progressive airway damage . Common bacterial pathogens, found in 50% to 60% of episodes, include Haemophilus influenzae (the most common), as well as Haemophilus parainfluenzae, Streptococcus pneumoniae and Moraxella catarrhalis . Bacterial resistance to antibiotics, especially beta-lactam drugs such as amoxicillin, is increasingly common in these pathogens . In this illness, clinical risk stratification based on age, history and comorbidity is an important strategy . Patients in the lowest risk group likely have viral infections and require no specific treatment . Patients in the higher risk groups require aggressive treatment to avoid treatment failure, which can lead to prolonged hospitalization and complications . Preventive therapies (smoking cessation and influenza vaccination) are worthwhile measures for these patients. Can Respir J, 1999 Jan-Feb, 6 Suppl A, 27A - 30A Evolving patterns of resistance to respiratory pathogens in Canada; Hoban DJ et al.; Active surveillance of changing resistance patterns is difficult but important for rational therapeutic choices . In Canada, penicillin resistance in Streptococcus pneumoniae has evolved more slowly than in other countries (in Europe and Israel rates exceed 50%) . Currently, penicillin resistance is found in roughly 21% of Canadian isolates, and cross-resistance is becoming common . Beta-lactamase production is now found in approximately 28% of Haemophilus influenzae isolates, although more recently, rates over 30% have been found in some areas of Canada . In Moraxella catarrhalis, beta-lactamases are produced by 80% to 90% of bacteria, with resistance to trimethoprim/sulphamethoxazole also found . To date, there have been only a few reports of resistance to the fluoroquinolones . The apparent increase in the rate of development of resistance and cross-resistance will lead to new therapeutic challenges. Can Respir J, 1999 Jan-Feb, 6 Suppl A, 23A - 6A Clinical implications of resistance in the management of respiratory tract infections; Garau J; Antibiotic resistance among the three major respiratory pathogens (Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis) has increased dramatically over the past 15 years, around the world . With S pneumoniae, penicillin resistance is reported in almost a quarter of isolates, with multiple resistance an increasing problem . The major concern with H influenzae is ampicillin resistance, mediated through two different mechanisms . In the case of M catarrhalis, beta-lactamase production is almost universal, although resistance to other antibiotics is rare . The increasing prevalence of resistance underscores the need for new effective antibiotics . The new quinolones have a spectrum of activity that parallels the range of common respiratory pathogens. Mol Microbiol, 1999 Mar, 31(5), 1477 - 88 Pneumococcal licD2 gene is involved in phosphorylcholine metabolism; Zhang JR et al.; Phosphorylcholine is an important bioactive adduct to the teichoic acid (TA) and lipoteichoic acid (LTA) of the surface of Streptococcus pneumoniae . We have identified and characterized a genetic locus lic that is required for phosphorylcholine metabolism in S . pneumoniae . The pneumococcal lic locus consists of eight genes, licA, licB, licC and licD1, licD2 and three additional open reading frames . Pneumococcal licA, licB, licC, licD1 and licD2 have significant sequence similarity to licA, licB, licC and licD of Haemophilus influenzae . Mutation of licD2 led to decreased {3H}-choline uptake, aberrant migration of LTA chains in SDS-PAGE gels, loss of several surface proteins, and a phase-locked hypertransparent colony phenotype . Moreover, the licD2- mutant falled to undergo lysis after treatment with penicillin at high cell density and showed decreased transformation competence . Finally, the licD2- mutant demonstrated decreased adherence to the human type II alveolar cells, reduced nasopharyngeal colonization in infant rats, as well as significantly impaired virulence upon intraperitoneal challenge of CF1 mice . Identification of the lic genes in the pneumococcus will facilitate further characterization of the role of surface choline in microbial physiology and pathogenesis. Infect Dis Clin North Am, 1999 Mar, 13(1), 113 - 33, vii Conjugated polysaccharide vaccines; Ahmad H et al.; The joining of polysaccharide antigens to various proteins can result in increased immunogenicity of vaccines composed of such antigens . This article discusses conjugated polysaccharide vaccines for Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitis . Increased availability and use of such vaccines may result in the ability to give more effective vaccines earlier in life, further reducing the incidence of diseases caused by these organisms. Curr Pharm Des, 1998 Apr, 4(2), 155 - 80 Recent developments in streptogramin research; Barriere JC et al.; The streptogramins are a class of antibiotics remarkable for their antibacterial activity and their unique mechanism of action . These antibiotics are produced naturally, but the therapeutic use of the natural compounds is limited because they do not dissolve in water . New semisynthetic derivatives, in particular the injectable streptogramin quinupristin/dalfopristin, offer promise for treating the rising number of infections that are caused by multiply resistant bacteria . The streptogramins consist of two structurally unrelated compounds, group A and group B . The group A compounds are polyunsaturated macrolactones: the group B compounds are cyclic hexadepsipeptides . Modifications of the group B components have been mainly performed on the 3-hydroxypicolinoyl, the 4-dimethylaminophenylalanine and the 4-oxo pipecolinic residues . Semi-synthesis on this third residue led to the water-soluble derivative quinupristin . Water-soluble group A derivatives were obtained by Michael addition of aminothiols to the dehydroproline ring of pristinamycin IIA . Followed by oxidation of the intermediate sulfide into the sulfone derivatives (i.e., dalfopristin) . Water-soluble derivatives (both group A and group B) can now be obtained at the industrial scale . Modified group B compounds are now also being produced by mutasynthesis, via disruption of the papA gene . Mutasynthesis has proved particularly useful for producing PIB, the group B component of the oral streptogramin RPR 106972 . The streptogramins inhibit bacterial growth by disrupting the translation of mRNA into protein . Both the group A and group B compounds bind to the peptidyltransferase domain of the bacterial ribosome . The group A compounds interfere with the elongation of the polypeptide chain by preventing the binding of aa-tRNA to the ribosome and the formation of peptide bonds, while the B compounds stimulate the dissociation of the peptidyl-tRNA and may also interfere with the release of the completed polypeptide by blocking its access to the channel through which it normally leaves the ribosome . The synergy between the group A and group B compounds appears to result from an enhanced affinity of the group B compounds for the ribosome . Apparently, the group A compound induces a conformational change such that B compound binds with greater affinity . The natural streptogramins are produced as mixtures of the group A and B compounds, the combination of which is a more potent antibacterial agent than either type of compound alone . Whereas the type A or type B compound alone has, in vitro and in animal models of infection, a moderate bacteriostatic activity, the combination of the two has strong bacteriostatic activity and often bactericidal activity . Minimal inhibitory concentrations of quinupristin/dalfopristin range from 0.20 to 1 mg/l for Streptococcus pneumonae, from 0.25 to 2 mg/l for Staphylococcus aureus and from 0.50 to 4 for Enterococcus faecium, the principal target organisms of this drug . Quinupristin/dalfopristin also has activity against mycoplasmas, Neisseria gonorrhoeae, Haemophilus influenz, Legionella spp . and Moraxella catarrhalis . Bacteria develop resistance to the streptogramms by ribosomal modification, by producing inactivating enzymes, or by causing an efflux of the antibiotic . Dimethylation of an adenine residue in rRNA, a reaction that is catalyzed by a methylase encoded by the erm gene class, affects the binding of group B compounds (as well as the macrolides and lincosamides; hence, MLSB resistance), but group A and B compounds usually maintain their synergy and their bactericidal effect against MLSB-resistant strains . erm genes are widespread both geographically and throughout numerous bacterial genera . Several types of enzymes (acetyltransferases, hydrolases) have been identified that inactivate the group A or the group B compounds . Genes involved in streptogramin efflux have so far been found only in staphylococci, particularly in coagulase-negative species Vaccine, 1999 Mar 17, 17(11-12), 1384 - 93 Safety and immunogenicity of combined diphtheria-tetanus-pertussis (whole cell and acellular)-Haemophilus influenzae-b conjugate vaccines administered to Indonesian children; Richie E et al.; A randomized double-blind trial was conducted to evaluate the safety and immunogenicity of vaccines comprised of diphtheria (D) and tetanus (T) toxoids combined with either a whole cell (P) or an acellular (aP) pertussis component and Haemophilus influenzae type b polyribosylphosphate (PRP) tetanus toxoid conjugate (PRP-T) in Indonesian infants . Three doses of either DTaP, DTaP-PRP-T, or DTP-PRP-T were administered to 930 infants approximately 2-3 months of age and at 2 month intervals thereafter . A booster dose of either DTP-PRP-T or DTaP-PRP-T was administered at 15-18 months of age . Both local and systemic reactions occurred at a significantly (p < 0.001-0.026) higher rate in the group that received whole cell pertussis vaccine versus groups which were immunized with aP containing vaccines . There was no significant difference (p > 0.05) in the rate of adverse events between groups immunized with DTaP or DTaP PRP T . One month after the third dose of vaccine, 99% of subjects had achieved > or =0.1 IU of anti-D and anti-T antibody per ml of serum . The geometric mean titer (GMT) to D was significantly (p < 0.001) higher in the group immunized with DTaP versus the other two groups whereas the anti-T GMT was significantly (p < 0.006) higher for the group immunized with DTP-PRP-T . Both the anti-pertussis toxin (PT) and anti-filamentous hemagglutinin (FHA) antibody levels were significantly (p < 0.001) higher in recipients of acellular versus whole cell pertussis vaccine . In contrast, the anti-B . pertussis agglutinating antibody response was significantly (p < 0.0001) higher in the group immunized with whole cell pertussis vaccine . The anti-PRP GMTs (microg antibody/ml) at 7 months were 0.096, 3.35 and 6.11 for groups immunized with DTaP, DTaP-PRP-T and DTP-PRP-T, respectively . The GMT for those immunized with DTP-PRP-T was significantly (p < 0.001) higher compared to recipients of DTaP-PRP-T . The percent of children who attained > or =0.15 or > or =1 microg/ml after immunization was 18 and 2% for the DTaP group, 93 and 76% for the DTaP-PRP-T group and 97 and 88% for the DTP-PRP-T group . At the > or =1 microg/ml level the difference between the DTaP-PRP0-T and DTP-PRP-T groups was significant (p < 0.01) . Children immunized with either DTaP, DTaP-PRP-T, or DTP-PRP-T were reimmunized with DTaP-PRP-T whereas a portion of children immunized with DTP PRP T where also boosted with this vaccine at 15-18 months of age . There was a vigorous anamnestic response to the D and T components with all children possessing > or =0.1 IU/ml . There was also a substantial increase in anti-PT, anti-FHA and B . pertussis agglutinating antibodies . The poorest anti-PT response was seen among children receiving DTP-PRP-T for both primary and reimmunization while the highest agglutinating antibody response followed receipt of 4 doses of DTP-PRP-T . Greater than 80% of children immunized with either DTP PRP T or DTaP-PRP-T possessed > or =0.15 microg/ml before boosting versus 38% for those vaccinated with DTaP (p < 0.001) . Primary immunization with DTP-PRP-T resulted in a significantly (p < 0.05) higher percentage (72%) maintaining > or =1 microg/ml compared to those immunized with DTaP-PRP-T (46%) . Prior to reimmunization, the anti-PRP GMT was significantly (p < 0.005) higher for children immunized with 3 doses of DTP-PRP-T versus DTaP-PRP-T . Subsequent to reimmunization, > or =95% of subjects attained > or =1 microg/ml. Vaccine, 1999 Mar 5, 17(9-10), 1169 - 78 Haemophilus influenzae type b conjugate vaccine stability: catalytic depolymerization of PRP in the presence of aluminum hydroxide; Sturgess AW et al.; The structural stability of the Haemophilus influenzae type b (Hib) capsular polysaccharide, polyribosylribitolphosphate (PRP) in an aluminum hydroxide adsorbed, polysaccharide-protein conjugate vaccine was monitored using modifications of an HPLC assay developed by Tsai et al . {Tsai C-M, Gu X-X, Byrd RA . Quantification of polysaccharide in Haemophilus influenzae type b conjugate and polysaccharide vaccines by high-performance anion-exchange chromatography with pulsed amperometric detection . Vaccine 1993;12:700-706.} . As applied to products containing PRP conjugated to the outer membrane protein complex (OMPC) from Neisseria meningitidis, this assay allows direct measurement of the total PRP content in very complex samples including commercial vaccine products . In addition, with the use of a high-speed centrifugation step, the assay can be used to directly quantify any PRP that is not conjugated to the OMPC carrier protein . These results provide evidence of what appears to be a catalytic reaction taking place between the phosphodiester bond of PRP and the aluminum hydroxide adjuvant that results in hydrolysis of the PRP polymer into smaller chain lengths and liberation of PRP oligomers from the conjugate particle . The reaction approaches an asymptotic limit after approximately two years at 2-8 degrees C . Clinical studies which span this time period confirm that the modest decrease in conjugated PRP content over time does not impact the overall clinical effectiveness of PRP-OMPC-containing vaccines. Int J Epidemiol, 1999 Feb, 28(1), 152 - 6 Protective effect of breastfeeding: an ecologic study of Haemophilus influenzae meningitis and breastfeeding in a Swedish population; Silfverdal SA et al.; BACKGROUND: In Orebro County, Sweden, a 2.5-fold increase in the incidence of Haemophilus influenzae (HI) meningitis was found between 1970 and 1980 . In a case-control study of possible risk factors for invasive HI infection conducted in the same area, 1987-1992, breastfeeding was found to be a strong protective factor . MATERIAL AND METHODS: In order to study the relation between incidence rates of HI meningitis between 1956-1992 and breastfeeding rates in the population an ecologic study was performed . RESULTS: A strong (negative) correlation between breastfeeding and incidence of HI infection 5 to 10 years later (rho(xy) (s) approximately -0.6) was seen, whereas no relation seems to exist for the time lag 15 years and beyond . The correlation for contemporary data was intermediate . There were similar results for the breastfeeding proportions at 2, 4 as well as 6 months of age . DISCUSSION: Our ecologic data are consistent with results from our case-control study . The time-lag for the delayed effect on the population level could be estimated although sparse data make the estimates vulnerable to sampling fluctuations . Limitations with ecologic studies are discussed . CONCLUSION: There seems to be an association between high breastfeeding rate in the population and a reduced incidence of HI meningitis 5 to 10 years later . These results do have implications on strategies for breastfeeding promotion, especially in countries where Hib vaccination is too costly and not yet implemented. Vaccine, 1999 Mar 5, 17(9-10), 1251 - 63 Size fractionation of bacterial capsular polysaccharides for their use in conjugate vaccines; Costantino P et al.; We have developed a chromatographic method suitable for the fractionation of polysaccharides having a negatively charged group . The method permits the removal of all those polysaccharide fragments having a short sequence and which are likely unsuitable for conjugate vaccine construction . The selected polysaccharide fragments can be used to produce glycoconjugate vaccines containing a restricted saccharide polydispersion . We have applied this chromatographic method to three different antigens, Haemophilus influenzae type b and Neisseria meningitidis group A and group C polysaccharides . The method is easily adapted for manufacturing purposes. Vaccine, 1999 Mar 26, 17(13-14), 1775 - 81 Killed whole bacterial cells, a mucosal delivery system for the induction of immunity in the respiratory tract and middle ear: an overview; Kyd JM et al.; Infectious diseases remain a leading cause of morbidity and mortality worldwide with mucosal membranes being the most frequent portals of entry of pathogenic micro-organisms . This has prompted studies aimed at the development of vaccination protocols that would lead to an increased protection of mucosae through an understanding of the common mucosal immune system as an immune communication network between mucosal sites . Recent studies have suggested that preferential sub-networks exist within the system and these studies have exploited the gut-associated lymphoid tissue (GALT)-lung sub-network in the development of oral vaccine strategies for infections of the respiratory tract and middle ear . Mucosal immunization with whole formalin killed Pseudomonas aeruginosa (Pa), Branhamella catarrhalis, nontypable Haemophilus influenzae (NTHi) or Streptococcus pneumoniae (Spn) results in enhanced homologous bacterial clearance from the lung of immune animals challenged with live bacteria . These studies have been extended to the middle ear where similar results have been observed for NTHi and Spn . Mechanisms responsible for inducing enhanced bacterial clearance from the airways include opsonising antibody, antigen specific CD4+ T helper cells, cytokine responses and recruitment of activated polymophonuclear neutrophils . The mechanisms induced by immunization which stimulates the immune system to rapidly mobilise both innate and specific immune responses during infection are the subject of ongoing research. Vaccine, 1999 Mar 26, 17(13-14), 1650 - 6 New acellular pertussis-containing paediatric combined vaccines; Pines E et al.; Combined pediatric vaccines have the advantages of conferring protection against multiple common infectious diseases with a reduced number of injections . Their use should lead to better compliance to recommended vaccination schedules . Diphtheria (D), tetanus (T) and whole-cell pertussis vaccine (P) have been successfully combined, with or without inactivated poliovirus vaccine (IPV) in the same syringe for many years . Recently developed acellular pertussis (aP) Haemophilus influenzae type B (Hib), inactivated poliomyelitis virus and hepatitis B vaccines are ideal candidates for inclusion in current combined vaccines . Nevertheless, the development of new combinations has to face preclinical and clinical issues: the appropriate formulation of the new antigen(s) and other vaccine components needs to be determined to ensure compatibility and guard against potential additive or unexpected adverse reactions; potential immunological interference between antigens and the negative impact of other vaccine components on immunogenicity may occur, and these have to be examined also . Whole-cell pertussis vaccines are highly protective against whooping cough, but the severe adverse reactions that these vaccines sometimes produce have led to hesitation over their use, including the decision of some countries to stop pertussis immunization . To increase the acceptability of pertussis vaccination, Pasteur Merieux Connaught has developed a combined D, T and a two-component acellular pertussis vaccine (DTaP), composed of purified pertussis toxoid (PT) and filamentous haemagglutinin (FHA), which has been shown to be effective in an efficacy trial conducted in Senegal . Acellular DTaP vaccines are immunogenic and have a better safety profile than DTP vaccines, when given either for the primary series, for the booster vaccination or for both . In order to meet worldwide demands, the combined DTaP-IPV or DTP-IPV has been developed for countries where IPV is recommended . Following the encouragement of the WHO, an H . influenzae type B tetanus-conjugated (Act-HIB) vaccine, has been combined in a full liquid formulation with the whole-cell DTP . This vaccine showed a good safety and immunogenicity profile in infants and in toddlers . A combined DTaP-IPV-PRP-T vaccine (where the Act-HIB vaccine is reconstituted by the full-liquid DTaP-IPV) also has been successfully developed both for the primary series and for booster vaccination; although, a reduced immunogenicity against PRP observed after the primary series, this did not affect vaccine priming . Hepatitis B immunization campaigns targeting high-risk groups have failed to control the disease in areas of low endemicity . In 1992, the WHO recommended that hepatitis B vaccination should be integrated into the EPI in all countries by 1997-1999 . For that purpose, hepatitis B vaccine is currently evaluated in pediatric combined vaccines . Developing new combination vaccines is a difficult but essential process for maintaining high immunization rates worldwide against infectious diseases, provided that the costs are acceptable . New combined vaccines including pneumococcal and meningococcal component are under wide-scale development. Vaccine, 1999 Mar 26, 17(13-14), 1620 - 7 Development and clinical application of new polyvalent combined paediatric vaccines; Andre FE; The availability of combined vaccines containing protective antigens against the majority of (ideally all) diseases for which universal immunization is recommended in infancy would simplify the implementation, increase the acceptance, reduce the global cost of immunization programmes and improve disease control, while offering the possibility of disease elimination or even pathogen eradication . The desirability of combined vaccines is further enhanced, and made more urgent, because of the increasing number of diseases that can be prevented by vaccination . The complicated logistics of administering different vaccines that each require several inoculations is a significant barrier to successful immunization of a population . Furthermore, interest in immunization is continuously gaining momentum since it is now generally recognised that vaccines are among the safest and most cost-effective medical interventions for infectious diseases that continue, in spite of the widespread use of efficacious antimicrobial drugs, to be an important cause of morbidity and mortality . This burden is likely to increase due to the development of antimicrobial resistance . Basic research on new vaccines or improvement of existing ones such as the use of new technologies may be carried out in academic or other non-industrial laboratories but development work, including the necessary extensive clinical testing, that lead to products that can be approved for routine use is usually co-ordinated and financed by commercial companies . The decision to develop any particular combined vaccine will therefore be influenced not only by its medical desirability and technical feasibility but also the potential financial returns that the required investments in time and resources may bring to the company . All major vaccine manufacturers are currently working, either alone or through strategic alliances, towards developing more polyvalent vaccines by adding antigens such as inactivated polio virus, conjugated Haemophilus influenzae type b polysaccharide and hepatitis B surface antigen to the diphtheria-tetanus-pertussis vaccine either in its 'classical' (whole-cell) or more purified (acellular) formulations . Experience is showing that the development of combined vaccines involves much more than the simple mixing of existing antigens . Possible incompatibilities or mutual interferences between the antigens themselves, or between excipients, preservatives, adjuvants, residual contaminants, stabilisers and suspending fluids make it mandatory that each formulation be thoroughly tested for quality, stability, efficacy and safety . Furthermore the ability to produce and control it consistently must be established before it can be licensed for commercial use . The progress being made in this field is reviewed. Biochemistry, 1999 Apr 6, 38(14), 4416 - 22 Chemical mechanism of Haemophilus influenzae diaminopimelate epimerase; Koo CW et al.; Seven unique enzymatic steps lead to the biosynthesis of L-lysine from L-aspartate semialdehyde and pyruvate in bacteria . The immediate precursor to L-lysine is D,L-diaminopimelate, a diamino acid which is incorporated into the pentapeptide of the Gram-negative peptidoglycan moiety . D,L-Diaminopimelate is generated from the corresponding L,L-isomer by the dapF-encoded epimerase . Diaminopimelate epimerase is a representative of the pyridoxal phosphate-independent amino acid racemases, for which substantial evidence exists supporting the role of two cysteine residues as the catalytic acid and base . The pH dependencies of the maximum velocities in the L,L --> D,L and D,L --> L,L direction depend on a single catalytic group exhibiting pK values of 7.0 and 6.1, respectively, which must be unprotonated for activity . The pH dependencies of the V/K values in both directions depend on the ionization of two groups, one exhibiting a pK value of 6.7 which must be unprotonated and one exhibiting a pK value of 8.5 which must be protonated . Primary kinetic isotope effects on V and V/K are unequal, with D(V/K) being larger than DV in both the forward and reverse directions . Solvent kinetic isotope effects in both directions are inverse on V/K, but normal on V . Both of these isotopic observations support a model in which proton isomerization after catalysis and substrate dissociation is kinetically significant . A single solvent "overshoot" is observed when L, L-diaminopimelate is incubated with enzyme in D2O; however, an unprecedented double overshoot is observed when D,L-diaminopimelate is incubated with enzyme in D2O . A model has been developed which allows these two overshoots to be simulated . A chemical mechanism is proposed invoking the function of two cysteine residues, Cys73 and Cys217, observed in the recently determined three-dimensional structure of this enzyme {Cirilli, M., et al . (1998) Biochemistry 37, 16452-16458}, as the acid and base in the mechanism. Am J Respir Crit Care Med, 1999 Apr, 159(4 Pt 1), 1199 - 204 Viruses and bacteria in bronchial samples from patients with primary hypogammaglobulinemia; Kainulainen L et al.; Viruses and bacteria in bronchoalveolar lavage fluids, protected specimen brush samples, and bronchial biopsies from 14 patients with primary hypogammaglobulinemia (11 patients with common variable immunodeficiency {CVID} and three patients with X-linked agammaglobulinemia {XLA}) were analyzed . At the time of the study, the patients had no signs of acute respiratory infections, and no antibiotics were administered . In addition to routine bacterial and viral cultures, polymerase chain reaction tests were used for the detection of adenovirus, cytomegalovirus (CMV), herpes simplex virus 1, enterovirus, rhinovirus, Borrelia burgdorferi, Chlamydia pneumoniae, Legionella spp., Mycoplasma pneumoniae, Pneumocystis carinii, and Ureaplasma urealyticum . Viruses (four adenoviruses, one CMV, and one rhinovirus) were detected in four of the 11 (36%) CVID patients . No viruses were found in the three patients with XLA or in 13 control patients . Bacteria from the lower respiratory tract were detected in nine of the 14 (64%) patients with hypogammaglobulinemia and three of the 13 (23%) control patients . Haemophilus influenzae was the most prevalent bacterium (43%) in the hypogammaglobulinemia patients . The study shows that patients with CVID harbor viral and bacterial infections in the lower respiratory tract, which may predispose to the development of changes in the respiratory tract. J Trop Pediatr, 1999 Feb, 45(1), 51 - 3 Acute bacterial meningitis in The Gambia: a four-year review of paediatric hospital admissions; Palmer A et al.; Over a 4 year period, 1991 to 1994, 420 patients with acute bacterial meningitis were admitted to a tertiary urban hospital in The Gambia . Organisms were isolated from the cerebrospinal fluid in 64 per cent of cases . In the neonatal period Streptococcus pneumoniae was the single most common organism isolated . Amongst infants and children the two major pathogens were Haemophilus influenzae and S . pneumoniae . In the first year of life, children with S . pneumoniae meningitis were younger than those with H . influenzae infection (median age 3 months versus 6 months, p < 0.00003) and they had a higher case fatality rate (37 per cent versus 17 per cent, p = 0.002) . In view of the high case fatality rate, there is a need to review overall case management . This will include a review of more effective antibiotics, the possible role of dexamethasone, and the inclusion of efficacious vaccines against H . influenzae and S . pneumoniae disease. J Infect Dis, 1999 May, 179(5), 1283 - 7 Experimental infection of human volunteers with Haemophilus ducreyi does not confer protection against subsequent challenge; Al-Tawfiq JA et al.; Two groups of human volunteers were inoculated with 2 doses of live Haemophilus ducreyi 35000HP . The reinfection group consisted of 7 subjects who previously had participated in experimental infection with 35000HP to the pustular stage of disease . The control group consisted of 7 naive subjects . Papules developed at 92.8% (95% confidence interval {CI}, 66.1%-99.8%) of sites inoculated with live bacteria, in the reinfection group, and at 85.7% (95% CI, 57.2%-98 . 2%) of sites in the control group . Sixty-nine percent (95% CI, 36 . 8%-90.9%) of papules evolved into pustules in the reinfection group, compared with 41% (95% CI, 15.2%-72.3%) in the control group . The recovery rates of H . ducreyi from surface cultures and the histopathology of biopsies obtained from both groups were similar . Thus, experimental infection to the pustular stage of disease does not provide protective immunity against subsequent challenge. Int J Pediatr Otorhinolaryngol, 1998 Nov 15, 46(1-2), 91 - 101 Topical ofloxacin versus systemic amoxicillin/clavulanate in purulent otorrhea in children with tympanostomy tubes; Goldblatt EL et al.; Acute otitis media (AOM) in children with tympanostomy tubes in place typically presents with otorrhea (draining ear) . Because therapy is not standardized, various topical and systemic antibiotics of unproven efficacy and safety have been used in this indication . This study compared the safety and efficacy of ofloxacin otic solution, 0.3% (OFLX) with that of Augmentin oral suspension (AUG) in pediatric subjects 1-12 years of age with tympanostomy tubes and acute purulent otorrhea . Subjects were randomized to receive 10d of OFLX, 0.25 ml topically bid, or of AUG, 40 mg/kg per day . Audiometry was performed in subjects > or =4 years of age . Overall cure rate for clinically evaluable subjects was 76% with OFLX (n = 140) and 69% with AUG (n = 146; P = 0.169) . Overall eradication rates for OFLX and AUG were similar for Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis and were superior with OFLX for Staphylococcus aureus and Pseudomonas aeruginosa (P<0.05 for both) . OFLX had a greater overall pathogen eradication rate (96% vs . 67%; P<0.001) . Treatment-related adverse event rates were 31% for AUG and 6% for OFLX (P<0.001) . Neither treatment significantly altered hearing acuity . Topical ofloxacin 0.3% otic solution 0.25 ml bid was as effective and better tolerated than systemic therapy with Augmentin oral suspension 40 mg/kg per day in treating AOM in children with tympanostomy tubes. Can J Med Technol, 1991, 53(4), 214 - 7 Comparison of two rapid methods used in the identification of Haemophilus and Moraxella species; Lankin D et al.; Both Haemophilus influenzae and Moraxella catarrhalis cause pneumonia in children and adults . The timely isolation and identification of these two organisms is important for the initiation of antibiotic therapy . This paper compares two commercial systems with traditional biochemical methods with respect to accuracy, cost and turn-around-time. Eur J Biochem, 1999 Apr, 261(1), 171 - 80 Structural analysis of the lipopolysaccharide oligosaccharide epitopes expressed by a capsule-deficient strain of Haemophilus influenzae Rd; Risberg A et al.; Structural elucidation of the lipopolysaccharide (LPS) of Haemophilus influenzae, strain Rd, a capsule-deficient type d strain, has been achieved by using high-field NMR techniques and electrospray ionization-mass spectrometry (ESI-MS) on delipidated LPS and core oligosaccharide samples . It was found that this organism expresses heterogeneous populations of LPS of which the oligosaccharide (OS) epitopes are subject to phase variation . ESI-MS of O-deacylated LPS revealed a series of related structures differing in the number of hexose residues linked to a conserved inner-core element, L-alpha-D-Hepp-(1-->2)-L-alpha-D-Hepp-(1-->3)-{beta-D-Glcp- (1-->4)-}- L-alpha-D-Hepp-(1-->5)-alpha-Kdo, and the degree of phosphorylation . The structures of the major LPS glycoforms containing three (two Glc and one Gal), four (two Glc and two Gal) and five (two Glc, two Gal and one GalNAc) hexoses were substituted by both phosphocholine (PCho) and phosphoethanolamine (PEtn) and were determined in detail . In the major glycoform, Hex3, a lactose unit, beta-D-Galp-(1-->4)-beta-D-Glcp, is attached at the O-2 position of the terminal heptose of the inner-core element . The Hex4 glycoform contains the PK epitope, alpha-D-Galp-(1-->4)-beta-D-Galp-(1-->4)-beta-D-Glcp while in the Hex5 glycoform, this OS is elongated by the addition of a terminal beta-D-GalpNAc residue, giving the P antigen, beta-D-GalpNAc-(1-->3)-alpha-D-Galp-(1-->4)-beta-D-Galp-(1-->4)-D-Glc p . The fully extended LPS glycoform (Hex5) has the following structure . {see text} The structural data provide the first definitive evidence demonstrating the expression of a globotetraose OS epitope, the P antigen, in LPS of H . influenzae . It is noteworthy that the molecular environment in which PCho units are found differs from that observed in an Rd- derived mutant strain (RM.118-28) {Risberg, A., Schweda, E . K . H . & Jansson, P-E . (1997) Eur . J . Biochem . 243, 701-707}. J Vet Diagn Invest, 1999 Mar, 11(2), 140 - 5 Development of an oligonucleotide-specific capture plate hybridization assay for detection of Haemophilus parasuis; Calsamiglia M et al.; An oligonucleotide-specific capture plate hybridization assay has been developed to rapidly, specifically, and sensitively detect Haemophilus parasuis from nasal swabs . Several in vitro studies have been performed to determine the sensitivity and specificity of the test, and in vivo studies have validated this technique in pigs . Results suggest that the assay detects <100 colony-forming units/ml in a pure culture and gives a positive result when H . parasuis is present in a ratio of 1:10(3)-10(4) in a mixed culture, and the probe does not hybridize with other related species found in the upper respiratory tract . This assay is more sensitive than culture for detection of the microorganism from nasal swabs and lesions. Yonsei Med J, 1998 Dec, 39(6), 611 - 8 Use of vaccine in the era of antimicrobial resistance: need of effective pneumococcal vaccines; Sohn YM; Streptococcus pneumoniae is an important pathogen causing invasive infections particularly in children . Penicillin-nonsusceptible pneumococci are very prevalent in Korea and a difficult problem in antimicrobial treatment . Immunization with effective vaccines including viral and bacterial vaccines has proven to be the most effective and reliable method to prevent the target disease . Universal immunization to infants with Haemophilus influenzae type b conjugate vaccine has dramatically proven to be very effective in reducing invasive Hib diseases and also the carriage rate . The 23-valent pneumococcal polysaccharide vaccine is effective in preventing invasive diseases in young adults and covers most of the penicillin-nonsusceptible types . It has not proven very effective in the prevention of otitis media, and is unable to elicit adequate antibody response in children younger than 2 years of age . Recently a new polysaccharide-protein conjugate vaccine was developed which can elicit antibody response in children younger than 2 years of age . However, the vaccine is only 8-valent at the moment . Studies are required to determine the possible idiotypic modulation and nonproductive immune response when polysaccharide vaccine is administered to infants . Part of the problem of antimicrobial-resistant pneumococcal infection may be solved in the future with the use of improved vaccine . Preventing pneumococcal infections with safe and effective vaccines will not only reduce the development of antibiotic resistance, but could also be the most cost-effective method to control pneumococcal disease. Antibiot Khimioter, 1999, 44(1), 14 - 9 {Etiology and treatment of pneumonia in children}; Tatochenko VK et al.; The most widespread pathogens of pneumonia in children i.e . Streptococcus pneumoniae and Haemophilus influenzae and their antibiotic susceptibility are described . The ways of selecting starting antibacterial drugs for the treatment of community-acquired and hospital pneumonia are recommended proceeding from the original findings and some literature data . Oral drugs for the treatment of uncomplicated pneumonia are shown to be preferential . In the tre