FEMS Immunol Med Microbiol, 2004 Jun 1, 41(2), 101 - 7 Human salivary aggregation in Streptococcus intermedius type g strains: relationship with IgA; Yamaguchi T; Bacterial aggregation is an important step in elimination from the human body to protect against infection . Streptococcus intermedius K1K aggregates in human saliva . In this study, the salivary agglutinin was identified . The aggregation level was very strong in sonic-treated saliva and 1-microm filtrate . Preincubation of human saliva with anti-human alpha chain serum or anti-human whole saliva serum completely inhibited aggregation, but preincubation with anti-human micro chain serum or anti-Fc fragment of human IgG serum had no effect . Agglutinin of human saliva that could aggregate the strain K1K was purified using DEAE-Sepharose CL-6B, Phenyl-Sepharose CL-4B and Sephacryl S200HR gel filtration . Purified salivary agglutinin was characterized with electrophoresis and immunological techniques, indicating that purified material was IgA . Bacterial aggregation was dependent on the presence of calcium . Saliva filtrate specimens from eight healthy men and eight women showed different aggregation activities . Three men and one woman had little activity . These data show that the present bacterial aggregation was an immunoreaction between IgA in saliva and the bacteria dependent on the levels of calcium . In addition, the IgA in human saliva related with possible calcium-dependent antigen(s) on the surface of strain K1K. Yakushigaku Zasshi, 2003, 38(2), 161 - 79 {The history of the development and changes of quinolone antibacterial agents}; Takahashi H et al.; The quinolones, especially the new quinolones (the 6-fluoroquinolones), are the synthetic antibacterial agents to rival the Beta-lactam and the macrolide antibacterials for impact in clinical usage in the antibacterial therapeutic field . They have a broad antibacterial spectrum of activity against Gram-positive, Gram-negative and mycobacterial pathogens as well as anaerobes . Further, they show good-to-moderate oral absorption and tissue penetration with favorable pharmacokinetics in humans resulting in high clinical efficacy in the treatment of many kinds of infections . They also exhibit excellent safety profiles as well as those of oral Beta-lactam antibiotics . The bacterial effects of quinolones inhibit the function of bacterial DNA gyrase and topoisomerase IV . The history of the development of the quinolones originated from nalidixic acid (NA), developed in 1962 . In addition, the breakthrough in the drug design for the scaffold and the basic side chains have allowed improvements to be made to the first new quinolone, norfloxacin (NFLX), patented in 1978 . Although currently more than 10,000 compounds have been already synthesized in the world, only two percent of them were developed and tested in clinical studies . Furthermore, out of all these compounds, only twenty have been successfully launched into the market . In this paper, the history of the development and changes of the quinolones are described from the first quinolone, NA, via, the first new quinolone (6-fluorinated quinolone) NFLX, to the latest extended-spectrum quinolone antibacterial agents against multi-drug resistant bacterial infections . NA has only modest activity against Gram-negative bacteria and low oral absorption, therefore a suitable candidate for treatment of systemic infections (UTIs) is required . Since the original discovery of NA, a series of quinolones, which are referred to as the old quinolones, have been developed leading to the first new quinolone, NFLX, with moderate improvements in over all properties starting in 1962 through and continuing throughout the 1970's . Especially, the drug design for pipemidic acid (PPA) indicated one of the important breakthroughs that lead to NFLX . The introduction of a piperazinyl group, which ia a basic moiety at the C7-position of the quinolone nuclei, improved activity against Gram-negative organisms broadening the spectrum to include Pseudomonas aeruginosa . PPA also showed soem activity against Gram-positive bac teria . The basic piperazine ring, which can form the zwitterionic natrure with the carboxylic acid at the C3-position, has subsequently been shown to increase the ability of the drugs to penetrate the bacterial cells resulting in enhanced activity . Further, the zwitterionic forms resulted in significant tissue penetration in the pharmacokinetics . On the other hand, the first compound with a fluorine atom at the C6-position of the related quinolone scaffold was flumequine and the compound indicated that activity against Gram-positive bacteria could be improved in the old quinolones . The addition of a flourine atom at the C6-position is essential for the inhibition of target enzymes . The results show the poten antibacterial activity and the penetration of the quinolone molecule into the bacterial cells and human tissue . The real breakthrough came with the combination of these two features in NFLX, a 6-fluorinated quinolone having a piperazinyl group at the C7-position, NFLX features significant differences from the old quinolones in the activities and pharmacokinetics in humans, resulting in high clinical efficacy in the treatment of many kinds of infections including RTIs.Consequently, those great discoveries are rapidly superseded by even better compounds and NFLX proved to be just the beginning of a highly successful period of research into the modifications of the new quinolone antibacterials . Simce the chemical structure and important features of NFLX had become apparent in 1978, many compounds were patented in the next three years, several of which reached the market . Among the drugs, ofloxacin (OFLX) and ciprofloxacin (CPFX) are recognized as superior in several respects to the oral beta-lactam antibiotics as an antibacterial agent . With a focus on OFLX and CPFX, numerous research groups entered the antibacterial therapeutic field, triggering intense competition in the search to find newer, more effective quinolones . After NFLX was introduced in the market, while resulting by the end of today, eleven kinds of other new quinolones launched in Japan . They are enoxacin (ENX), OFLX, CPFX, lomefloxacin (LFLX), fleroxacin (FRLX), tosufloxacin (TFLX), levofloxacin (LVFX), sparfloxacin (SPFX), gatifloxacin (GFLX), prulifloxacin (PULX) and also pazufloxacin (PZFX) . The advantages of these compounds, e.g., LVFX, SPFX and GFLX, are that their spectrum includes Gram-positive bacteria species as well as Gram-negative bacteria and they improve bioavailability results when a daily dose is administered for systemic infections including RTIs . However, unexpected adverse reactions, such as the CNS reaction, the drug-drug interaction, phototoxicity, hepatotoxicity and cardiotoxicity such as the QTc interval prolongation of ECG, have been reported in the clinical evaluations or the post-marketing surveillance of several new quinolones . Moreover, the adverse reactions of arthropathy (the joint toxicity) predicated from studies in juvenile animals have never materialized in clinical use . Therefore, no drugs other than NFLX have yet been approved for pediatric use . Fortunately, the newer quinolones are being developed and tested to reduce these adverse reactions on the basis of recent studies . On the other hand, multi-drug resistant Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant coagulase-negative staphycolocci (MRCNS), penicillin-resistant Streptococcus pneumoniae (PRSP) and vancomycin-resistant enterococci (VRE) have been a serious problem in the medical community . Recently, the new quinolone antibacterials are highly successful class of antibacterial therapeutic field, however, the increased isolation of quinolone-resistant bacteria above them has become a normal outcome . These problems of multi-drug resistance have been the driving force for the development of newer quinolones . The next gereration of quinolone antibacterial agents will be potent against multi-drug resistant bacteria, such as MRSA, and provide a lower rate of emergence in resistance . Further, they should have favorable safety profiles to reduce the adverse reactions . The future of quinolones as the ultimate in pharmaceuticals must be handled cautiously if they are to realize their potential in the medical community. Curr Infect Dis Rep, 2004 Jun, 6(3), 191 - 199 The Use of Ketolides in Treatment of Upper Respiratory Tract Infections; Zhanel GG et al.; Recent surveillance studies suggest that the incidence of resistance to macrolide antibiotics in common community-acquired respiratory tract pathogens, particularly Streptococcus pneumoniae and Streptococcus pyogenes, is increasing and limiting the usefulness of these drugs . The ketolides, of which telithromycin is the first to be available for clinical use (but not yet in the United States), represent a new class of antibacterials developed specifically to combat respiratory tract pathogens that have acquired resistance to macrolides . The ketolides possess innovative structural modifications, a 3-keto group and a large N-substituted C11, C12-carbamate side chain . This novel structure allows ketolides, which are inhibitors of protein synthesis, to exert a more effective interaction with domain II of the 23S rRNA, enhancing binding to bacterial ribosomes and allowing binding to macrolide-lincosamide-streptogramin B-resistant ribosomes . This novel chemical structure also promotes greater stability of telithromycin in acid conditions, providing the potential for greater stability in gastric fluid and at cellular/tissue levels . Early clinical trials support the bacteriologic and clinical efficacy of telithromycin in the treatment of upper respiratory tract infections (RTIs) such as streptococcal pharyngitis and acute sinusitis, including infections caused by macrolide-resistant S . pneumoniae and S . pyogenes . Common adverse side effects associated with telithromycin are predominantly gastrointestinal, usually of mild to moderate severity, and rarely involve withdrawal of the drug . Telithromycin represents an attractive option for the empiric treatment of upper RTIs, especially as resistance to macrolides is likely to continue to increase. J Clin Periodontol, 2004 Jun, 31(6), 420 - 7 Antibiotic resistance profile of the subgingival microbiota following systemic or local tetracycline therapy; Rodrigues RM et al.; BACKGROUND: Tetracyclines have been extensively used as adjunctives to conventional periodontal therapy . Emergence of resistant strains, however, has been reported . This study evaluated longitudinally the tetracycline resistance patterns of the subgingival microbiota of periodontitis subjects treated with systemic or local tetracycline therapy+scaling and root planing (SRP) . METHODS: Thirty chronic periodontitis patients were randomly assigned to three groups: SRP+500 mg of systemic tetracycline twice/day for 14 days; SRP alone and SRP+tetracycline fibers (Actsite) at four selected sites for 10 days . Subgingival plaque samples were obtained from four sites with probing pocket depths (PPD)> or =6 mm in each patient at baseline, 1 week, 3, 6 and 12 months post-therapy . Samples were dispersed and diluted in pre-reduced anaerobically sterilized Ringer's solution, plated on Trypticase Soy Agar (TSA)+5% blood with or without 4 microg/ml of tetracycline and incubated anaerobically for 10 days . The percentage of resistant microorganisms were determined and the isolates identified by DNA probes and the checkerboard method . Significance of differences among and within groups over time was sought using the Kruskal-Wallis and Friedman tests, respectively . RESULTS: The percentage of resistant microorganisms increased significantly at 1 week in the tetracycline groups, but dropped to baseline levels over time . The SRP+Actsite group presented the lowest proportions of resistant species at 6 and 12 months . No significant changes were observed in the SRP group . The predominant tetracycline-resistant species included Streptococcus spp., Veillonela parvula, Peptostreptococcus micros, Prevotella intermedia, Gemella morbillorum and Actinobacillus actinomycetemcomitans (Aa) . A high percentage of sites with resistant Aa, Porphyromonas gingivalis and Tanerella forsythensis was observed in all groups at baseline . However, T . forsythensis was not detected in any group and P . gingivalis was not present in the SRP+Actsite group at 1 year post-therapy . Aa was still frequently detected in all groups after therapy . However, the greatest reduction was observed in the SRP+Actsite group . CONCLUSION: Local or systemically administered tetracycline results in transitory selection of subgingival species intrinsically resistant to this drug . Although the percentage of sites harboring periodontal pathogens resistant to tetracycline were quite elevated in this population, both therapies were effective in reducing their prevalence over time. Ceska Gynekol, 2004 Mar, 69(2), 91 - 4 {Screening for hemolytic streptococcus group B in pregnancy and prevention of infection in neonates}; Janek L et al.; OBJECTIVE: The aim of this study was to evaluate the influence of Group B streptococcus (GBS) screening and intrapartum antibiotic prophylaxis to the incidence of GBS disease in newborns . DESIGN: Prospective non-randomised study . SETTING: IInd Clinic of Obstetric and Gynaecology LFUK and FNsP Ruzinov, Bratislava, Slovakia . METHODS: We enrolled 3023 newborns (754 in the study group, 2269 in the control group), which were born between 1.9.2000 and 31.3.2003 . In both groups we compared following variables: total number of infectious diseases in newborns, number and forms of GBS neonatal disease, number of perinatal death due to GBS disease . RESULTS: There was no GBS disease in the study group of 754 newborns . Mothers of these newborns had one screening culture in 35-36th week of gestation . One swab was taken from vagina and anus . GBS carriers (161-21.4%) were administered i.v . intrapartum antibiotic prophylaxis with Penicillin G i.v., or, when allergy to penicillin was in history, with Clindamycin i.v . In the control group of 2269 newborns, whose mothers had no prevention, the incidence of GBS neonatal disease reached 7.5/1000 newborns (17 cases) . The incidence of invasive GBS neonatal disease was 2.6/1000 newborns . CONCLUSION: The authors have noticed a significant decrease in incidence of GBS neonatal disease after implication of GBS screening and intrapartum antibiotic prophylaxis. J Perinatol, 2004 Jul, 24(7), 441 - 5 The histologic fetoplacental inflammatory response in fatal perinatal group B-streptococcus infection; De Paepe ME et al.; OBJECTIVE: To determine the rate of histologic fetoplacental inflammation in fetuses and newborns with fatal perinatal Group B-Streptococcus (GBS) infection . STUDY DESIGN: Autopsy files (1990 to 2002) were searched for fetuses and newborns with GBS-positive post-mortem blood and/or lung cultures . The rate of histological fetoplacental inflammation in preterm (< 36 weeks gestational age) and term (> or =36 weeks) fetuses/infants was compared using chi(2) test . RESULTS: GBS infection was diagnosed in 4.9% (61/1236) of perinatal autopsies and was considered the exclusive cause of death in 58 cases (16 to 41 weeks gestation, median: 26 weeks) . A total of 43 fetuses/infants (74%) were preterm, 24 (41%) were male and 33 (57%) stillborn . The histologic fetoplacental inflammatory response was age-dependent for the following variables: acute chorioamnionitis (seen in 67% of preterm vs 33% of term fetuses/infants, p < 0.05), multiple-vessel umbilical vasculitis (37 vs 7%, p < 0.05), funisitis (37 vs 13%, p < 0.05), and the presence of neutrophils in the gastrointestinal tract (35% vs none, p < 0.05) . Neutrophils in the pulmonary airspaces (47 vs 33%) and pneumonia (16 vs 27%) were found with similar frequency in both groups . CONCLUSION: Histologic fetoplacental inflammation is a poor indicator of perinatal GBS infection; the sensitivity is 67% in preterm and 33% in term fetuses/newborns (overall sensitivity 59%) . The higher rate of histologic inflammation in preterm fetuses/newborns suggests age-specific interactions between microorganism, host and placenta. J Antimicrob Chemother, 2004 Jul, 54(1), 247 - 50 Epub 2004 May 12. Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae in Austria; Buxbaum A et al.; OBJECTIVES: To determine the prevalence of antibiotic resistance and the distribution of serotypes among Streptococcus pneumoniae isolated in Austria . MATERIALS AND METHODS: A total of 2367 strains of S . pneumoniae were collected in an Austrian-wide surveillance system between 1996 and 2002 . Isolates were tested for their susceptibility to penicillin and clarithromycin and were serotyped by the capsular swelling method . RESULTS: An overall rise in penicillin resistance was observed from 4.9% in 1996 to 10.0% in 2002 (including both intermediate-resistant and resistant strains) . A rise in clarithromycin resistance was also recorded in this period . The overall distribution of serogroups/types remained relatively stable, with 23, 19, 6 and 14 being the most frequent ones . Whereas in 1996 penicillin resistance was predominantly associated with serotype 23F, in 1998 and 2002, resistance was most frequently found in isolates of serogroup 9 and serotype 14, respectively . Coverage rates for currently available vaccines ranged from 57.4% (7-valent) to 72.4% (23-valent) of all serotyped strains . CONCLUSIONS: This rise in pneumococcal resistance to penicillin and clarithromycin, and the change in distribution of serotypes in these resistant strains, indicates that ongoing surveillance programmes are warranted, in order to be able to formulate both effective vaccination strategies and optimal antibiotic therapies. Microb Drug Resist, 2004 Spring, 10(1), 37 - 42 Fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae from Asian countries: ANSORP study; Oh WS et al.; Seventeen clinical isolates of Streptococcus pneumoniae showing reduced susceptibility to ciprofloxacin (MIC >/= 4 micro g/ml) collected from eight different Asian countries were analyzed by antimicrobial susceptibility, serotyping, pulsed-field gel electrophoresis (PFGE), and DNA sequencing of the quinolone resistance-determining regions (QRDRs) in gyrA, gyrB, parC, and parE . All isolates but one showed more than one amino acid alteration in QRDRs of four responsible genes . Ile460 --> Val in parE was the most common mutation . Data suggest that Lys137 --> Asn in parC may be a primary step in the development of high-level and multiple FQ resistance . An additional mutation of Ser81 --> Phe in gyrA resulted in high-level resistance to ciprofloxacin, levofloxacin, and gatifloxacin, whereas Ser79 --> Phe in parC may exert an important role in the development of moxifloxacin resistance . Two novel amino acid changes in gyrB, Ala390 --> Val and Asn423 --> Thr, were found . Data from PFGE suggest an introduction and local spread of multiple resistant Spain(23F)-1 clone in Hong Kong, but isolates from other Asian countries were not related to this clone. Ann R Coll Surg Engl, 2004 May, 86(3), 196 - 201 Intra-operative culture in appendicitis: traditional practice challenged; Gladman MA et al.; INTRODUCTION: Traditionally, microbiological swabs are taken for culture during appendicectomy . However, the pathogens encountered are largely predictable, and sensitive to broad-spectrum antibiotics . Thus, we aimed to examine the clinical value of this practice, by determining the influence of microbiological results on postoperative outcome in patients undergoing appendicectomy . PATIENTS AND METHODS: The study population comprised 721 consecutive patients undergoing appendicectomy for suspected acute appendicitis in a single district general hospital . Microbiological culture results and sensitivities of isolates were recorded in relation to histopathological findings and infective morbidity, to establish whether they influenced postoperative outcome . RESULTS: Swabs were taken during 463 (64%) appendicectomies . Only 113 (24%) yielded positive cultures ('coliforms', anaerobes and Streptococcus milleri were most frequently isolated) . Organisms resistant to broad-spectrum antibiotics were encountered in only 11 of 463 patients (2%) where swabs were taken . Overall, 39 patients (5%) developed significant infective complications postoperatively . Neither the presence of a positive intra-operative culture, nor the isolation of resistant organisms were significant in predicting infective complications (P = 0.11 and 0.17, respectively) . CONCLUSIONS: In the population studied, the results of intra-operative culture did not influence clinical outcome in patients undergoing appendicectomy . The practice of taking routine microbiological swabs for culture must be seriously questioned. JAMA, 2004 May 12, 291(18), 2197 - 203 Impact of childhood vaccination on racial disparities in invasive Streptococcus pneumoniae infections; Flannery B et al.; CONTEXT: Historically, incidence of pneumococcal disease in the United States has been higher among blacks than among whites . Following recommendation of a new 7-valent pneumococcal conjugate vaccine for children in October 2000, the incidence of invasive pneumococcal disease has declined dramatically, but the impact of vaccination on racial disparities in incidence of pneumococcal disease is unknown . OBJECTIVE: To assess the effect of conjugate vaccine introduction on rates of pneumococcal disease among whites and blacks in the United States . DESIGN, SETTING, AND PATIENTS: Analysis of data from the Active Bacterial Core Surveillance (ABCs)/Emerging Infections Program Network, an active, population-based surveillance system in 7 states . Patients were 15,923 persons with invasive pneumococcal disease occurring between January 1, 1998, and December 31, 2002 . MAIN OUTCOME MEASURES: Age- and race-specific pneumococcal disease incidence rates (cases per 100 000 persons), rate ratios, and rate differences . RESULTS: Between 1998 and 2002, annual incidence rates for invasive pneumococcal disease decreased from 19.0 to 12.1 cases per 100 000 among whites and from 54.9 to 26.5 among blacks . Due to these declines, 14,730 fewer cases occurred among whites and 8780 fewer cases occurred among blacks in the United States in 2002, compared with 2 prevaccine years, 1998 and 1999 . Before vaccine introduction, incidence among blacks was 2.9 times higher than among whites (95% confidence interval {CI}, 2.7-3.0); in 2002, the black-white rate ratio had been reduced to 2.2 (95% CI, 2.0-2.4) . Incidence among black children younger than 2 years went from being 3.3 times higher (95% CI, 3.0-3.7) than among white children in the prevaccine period to 1.6 times higher (95% CI, 1.1-2.2) in 2002 . By 2002, 74% of white children and 68% of black children aged 19 to 35 months in the 7 states had received at least 1 dose of pneumococcal conjugate vaccine; 43% of white and 39% of black children received 3 or more doses . CONCLUSION: Although blacks remain at higher risk of invasive pneumococcal disease, introduction of childhood pneumococcal vaccination has reduced the racial disparity in incidence of pneumococcal disease. J Ethnopharmacol, 2004 Jun, 92(2-3), 331 - 5 Effect of Powerdental on caries-inducing properties of Streptococcus mutans and TNF-alpha secretion from HMC-1 cells; You YO et al.; We studied the inhibitory effect of Powerdental on the growth and acid production of Streptococcus mutans as well as secretion of pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) . The growth of Streptococcus mutans was reduced by the presence of the Powerdental (1 mg/ml) and NaCl (1 mg/ml) significantly, and the positive control group (1% NaF) also exhibited a significant antibacterial activity . The decrease of pH was significantly inhibited in the presence of Powerdental (1 mg/ml) compared to the control group . The decrease in pH was also inhibited in the presence of positive control (1% NaF), but the bamboo salt alone did not show inhibitory activity . We also found that Powerdental (0.01 mg/ml) inhibited significantly the secretion of TNF-alpha with 46.5+/-0.2% from human mast cells . Our results suggest that Powerdental contributes to the prevention or treatment of periodontitis and other oral diseases or inflammatory diseases. J Ethnopharmacol, 2004 Jun, 92(2-3), 281 - 9 Inhibitory effect of some herbal extracts on adherence of Streptococcus mutans; Limsong J et al.; The objective of this study was to investigate the inhibitory effect of the crude extracts from some herbs on adherence of Streptococcus mutans (S . mutans) ATCC 25175 and TPF-1 in vitro . Six herbs, Andrographis paniculata; Cassia alata; Chinese black tea (Camellia sinensis); guava (Psidium guajava); Harrisonia perforata and Streblus asper, were extracted with 50 or 95% ethanol and dried . Herbal extracted solution at 0.5% concentration (w/v) was initially tested for bacterial adherence on glass surfaces . In order to identify type and effective concentration of the extracts, the extracts that showed the inhibition on glass surfaces were then tested on saliva-coated hydroxyapatite by the use of radiolabeled bacteria . To study the mechanism of action, the effect of the extracts at such concentration on glucosyltransferase and glucan-binding lectin activities were examined . It was found that all extracts, but Streblus asper, showed significant inhibitory effect on bacterial adherence to glass surfaces . For the saliva-coated hydroxyapatite adherence assay, Andrographis paniculata, Cassia alata, Chinese black tea and Harrisonia perforata could inhibit adherence of S . mutans ATCC 25175 . Chinese black tea was the strongest inhibitor followed by Andrographis paniculata, Cassia alata and Harrisonia perforata, respectively . For S . mutans TPF-1, adherence inhibition was observed from Andrographis paniculata and Cassia alata at similar levels . The lowest concentrations of the extracts that inhibited the adherence at least 50% were 0.5% of Andrographis paniculata, 0.5% of Cassia alata, 0.3% of Chinese black tea and 0.5% of Harrisonia perforata for S . mutans ATCC 25175 . For S . mutans TPF-1, the effective concentrations were 0.5% of Andrographis paniculata and 0.4% of Cassia alata . All extracts at such concentrations decreased the activity of glucosyltransferase from both strains . Only Andrographis paniculata and Cassia alata eliminated or decreased the activity of glucan-binding lectin from both strains . These findings suggested that Andrographis paniculata, Cassia alata, Chinese black tea and Harrisonia perforata could inhibit adherence of S . mutans ATCC 25175, while Andrographis paniculata and Cassia alata had an effect on S . mutans TPF-1 in vitro at the concentrations employed in this study. Vet Ther, 2003 Fall, 4(3), 299 - 308 Efficacy of extended pirlimycin therapy for treatment of experimentally induced Streptococcus uberis intramammary infections in lactating dairy cattle; Oliver SP et al.; Streptococcus uberis is an important cause of mastitis in dairy cows throughout the world, particularly during the dry period, around the time of calving, and during early lactation . Strategies for controlling S . uberis mastitis have not received adequate research attention and are therefore poorly defined and inadequate . Objectives of the present study were to evaluate the efficacy of extended therapy regimens with pirlimycin for treatment of experimentally induced S . uberis intramammary infections in lactating dairy cows during early lactation and to evaluate the usefulness of the S . uberis experimental infection model for evaluating antimicrobial efficacy in dairy cows . The efficacy of extended pirlimycin intramammary therapy regimens was investigated in 103 mammary glands of 68 dairy cows that became infected following experimental challenge with S . uberis during early lactation . Cows infected with S . uberis in one or both experimentally challenged mammary glands were randomly allocated to three groups, representing three different treatment regimens with pirlimycin, including 2-day (n = 21 cows, 31 mammary quarters), 5-day (n = 21 cows, 32 quarters), and 8-day (n = 26 cows, 40 quarters) . For all groups, pirlimycin was administered at a rate of 50 mg of pirlimycin hydrochloride via intramammary infusion . A cure was defined as an experimentally infected mammary gland that was treated with pirlimycin and was bacteriologically negative for the presence of S . uberis at 7, 14, 21, and 28 days after treatment . Experimental S . uberis intramammary infections were eliminated in 58.1% of the infected quarters treated with the pirlimycin 2-day regimen, 68.8% for the 5-day regimen, and 80.0% for the 8-day regimen . Significant differences (P <.05) in efficacy were observed between the 2-day and 8-day treatment regimens . The number of somatic cells in milk decreased significantly following therapy in quarters for which treatment was successful in eliminating S . uberis . However, there was no evidence to suggest that extended therapy with pirlimycin resulted in a greater reduction in somatic cell counts in milk than the 2-day treatment . The S . uberis experimental infection model was a rapid and effective means of evaluating antimicrobial efficacy during early lactation at a time when mammary glands are highly susceptible to S . uberis intramammary infection. Chest, 2004 May, 125(5), 1888 - 901 Guidelines for empiric antimicrobial prescribing in community-acquired pneumonia; File TM Jr et al.; Empiric antimicrobial prescribing for community-acquired pneumonia remains a challenge, despite the availability of treatment guidelines . A number of key differences exist between North American and European guidelines, mainly in the outpatient setting . The North American approach is to use initial antimicrobial therapy, which provides coverage for Streptococcus pneumoniae plus atypical pathogens . Europeans tend to focus on providing pneumococcal coverage with less emphasis on covering for an atypical pathogen . Ambulatory patients without comorbidity are more likely to receive macrolide therapy in North America, whereas in Europe these patients would probably receive a beta-lactam agent . Major issues that are fundamental to this difference include the importance of providing therapy for atypical pathogens and the clinical significance of macrolide-resistant S pneumoniae . Prospective data are required to evaluate which of these two approaches offers clinical superiority. FEMS Microbiol Lett, 2004 May 15, 234(2), 315 - 24 An ffh mutant of Streptococcus mutans is viable and able to physiologically adapt to low pH in continuous culture; Crowley PJ et al.; Previously, we described in Streptococcus mutans strain NG8 a 5-gene operon (sat) that includes ffh, the bacterial homologue of the eukaryotic signal recognition particle (SRP) protein, SR54 . A mutation in ffh resulted in acid sensitivity but not loss of viability . In the present study, chemostat-grown cells of the ffh mutant were shown to possess only 26% and 39% of the parental membrane F-ATPase activity and 55% and 75% of parental glucose-phosphotransferase (PTS) activity when pH-7 and pH-5-grown cells, respectively, were assayed . Two-dimensional-gel electrophoretic analyses revealed significant differences in protein profiles between parent and ffh-mutant strains at both pH 5 and pH 7 . It appears that the loss of active SRP (Ffh) function, while not lethal, results in substantial alterations in cellular physiology that includes acid tolerance . Diagn Microbiol Infect Dis, 2004 May, 49(1), 53 - 8 Antimicrobial susceptibility patterns of Streptococcus pneumoniae in Mexico; Quinones-Falconi F et al.; The susceptibility to 14 beta-lactam and non-beta-lactam antimicrobial agents was evaluated for Streptococcus pneumoniae from patients with community-acquired respiratory infections in a Mexican medical center . Three hundred fifteen pneumococcal isolates obtained from patients between 1995 and 2001 were tested by the broth microdilution test . Fifty-two percent of the isolates were nonsusceptible to penicillin (minimal inhibitory concentration, >0.06 microg/mL) . Penicillin-nonsusceptible isolates were more likely to exhibit resistance to cephalosporins, macrolides, ciprofloxacin, trimethoprim/sulfamethoxazole, chloramphenicol, and tetracycline when compared to penicillin-susceptible isolates . Ninety-three percent of the penicillin-nonsusceptible isolates were resistant to at least one other class of antimicrobials, in contrast to only 47% of the penicillin-susceptible strains (p < 0.0001) . More than 90% of the tested isolates were susceptible to amoxicillin/clavulanate, ceftriaxone, levofloxacin, and gatifloxacin . Reduced susceptibility to penicillin was considered to be a reliable marker for the higher probability of multidrug resistance, thus requiring in vitro tests to guide chemotherapy or the choices of parenteral extended spectrum cephalosporins or newer respiratory quinolones. Diagn Microbiol Infect Dis, 2004 May, 49(1), 47 - 52 Epidemiology of macrolide and/or lincosamide resistant Streptococcus pneumoniae clinical isolates with ribosomal mutations; Doktor SZ et al.; Twenty macrolide and/or lincosamide resistant Streptococcus pneumoniae clinical isolates from various sources with 50S ribosomal mutations were identified . Mutations were identified in the 23S rDNA with substitutions at A2058, A2059, or C2611 and in L4 or L22 ribosomal protein genes . Fourteen were A2059G substitutions, one was A2058G, two were C2611T, two had an altered L4 and one isolate contained an altered L22 gene . Susceptibility testing with erythromycin, josamycin, clindamycin, and two ketolides including cethromycin was performed . The L4 mutants had the amino acid changes of (69)GTG(71) to (69)TPS(71) . The isolate with the L22 mutation contained an 18 base pair tandem duplication/insertion at the 3' end of the gene . 50s ribosomal mutations are the least frequent mechanism of S . pneumoniae resistance, occurring at an extremely low frequency and are identified only by genome sequence data. Mol Cell Probes, 2004 Jun, 18(3), 147 - 53 Streptococcus pneumoniae in nasopharyngeal secretions of healthy children: comparison of real-time PCR and culture from STGG-transport medium; Saukkoriipi A et al.; Precise methods for the detection of Streptococcus pneumoniae are needed for predicting the consequences of pneumococcal conjugate vaccines on nasopharyngeal carriage . In this study, 400 nasopharyngeal swab samples from children were analyzed using a real-time pneumolysin (ply)-PCR method . The specimens were originally collected into STGG-transport medium and cultured in 1999, after which they were stored at -80 degrees C until analyzed by real-time PCR in 2001 . The sensitivities of real-time PCR and culture methods were also studied by analyzing 10-fold dilutions of a pneumococcal broth culture using both methods . Of the 400 nasopharyngeal swab samples, 158 (40%) were positive in culture and 276 (69%) by real-time PCR . A minor part (4%) of the culture-positive samples remained negative by PCR . There was a trend between the quantity of genome equivalents detected by PCR and the number of colonies found in culture . When analyzing 10-fold dilutions of a pneumococcal broth culture, a higher number of genome equivalents were detected using real-time PCR than the number of colonies detected by culture . Quantitative real-time PCR provides feasible means for quantifying pneumococcal carriage . Further studies are needed to confirm that positive PCR findings really indicate the presence of viable pneumococcus in nasopharyngeal specimens. Drugs Exp Clin Res, 2004, 30(1), 17 - 26 Evaluation of the degree of susceptibility of Streptococcus pyogenes erythromycin-resistant strains to rokitamycin (a 16-membered macrolide) using the Epsilometer test; Crotti D et al.; Routine hospital screening of the resistance of Streptococcus pyogenes to macrolides is usually done using the erythromycin, clarithromycin or azithromycin disk diffusion technique . When a strain is found to be resistant to one of these macrolides, it is generally assumed to be resistant to the whole class . However this approach gives only partial qualitative information because S . pyogenes strains with inducible and M phenotype resistance are still susceptible to 16-membered ring macrolides such as rokitamycin . Seventy-four erythromycin-resistant (22 inducible and 52 M phenotype) strains of S . pyogenes were tested for their susceptibility to rokitamycin and clindamycin (control) by means of the agar disk diffusion test and the results were compared with those obtained using the Epsilometer test, a quantitative technique for measuring bacterial susceptibility and minimal inhibitory concentrations (MIC) . Epsilometer testing of erythromycin in comparison with rokitamycin is useful for measuring the real degree of susceptibility of macrolide-resistant strains quickly and simply . This is important because strains with the same disk diffusion diameter do not necessarily have the same MIC, but a scattered distribution of susceptibility. Microbiology, 2004 May, 150(Pt 5), 1559 - 69 SpeB modulates fibronectin-dependent internalization of Streptococcus pyogenes by efficient proteolysis of cell-wall-anchored protein F1; Nyberg P et al.; SpeB is a cysteine proteinase and virulence determinant secreted by the important human pathogen Streptococcus pyogenes . Recent investigations have suggested a role for SpeB in streptococcal entry into human cells . However, conflicting data concerning the contribution of SpeB to internalization have been presented . Protein F1 is a cell-wall-attached fibronectin (Fn)-binding protein that is present in a majority of streptococcal isolates and is important for internalization . This study shows that protein F1 is efficiently degraded by SpeB, and that removal of protein F1 from the bacterial surface leads to reduced internalization . Whereas M1 protein and protein H, two additional surface proteins of S . pyogenes that bind human plasma proteins, are protected from proteolytic degradation by their ligands, protein F1 is readily cleaved by SpeB also when in complex with Fn . This finding, and the connection between the presence of Fn at the bacterial surface and entry into human cells, suggest that SpeB plays a role in the regulation of the internalization process. Microbiology, 2004 May, 150(Pt 5), 1353 - 66 Proteome analysis of Streptococcus mutans metabolic phenotype during acid tolerance; Len AC et al.; Two-dimensional gel electrophoretic analysis of the proteome of Streptococcus mutans grown at a steady state in a glucose-limited anaerobic continuous culture revealed a number of proteins that were differentially expressed when the growth pH was lowered from pH 7.0 to pH 5.0 . Changes in the expression of metabolic proteins were generally limited to three biochemical pathways: glycolysis, alternative acid production and branched-chain amino acid biosynthesis . The relative level of expression of protein spots representing all of the enzymes associated with the Embden-Meyerhof-Parnas pathway, and all but one of the enzymes involved in the major alternative acid fermentation pathways of S . mutans, was identified and measured . Proteome data, in conjunction with end-product and cell-yield analyses, were consistent with a phenotypic change that allowed S . mutans to proliferate at low pH by expending energy to extrude excess H(+) from the cell, while minimizing the detrimental effects that result from the uncoupling of carbon flux from catabolism and the consequent imbalance in NADH and pyruvate production . The changes in enzyme levels were consistent with a reduction in the formation of the strongest acid, formic acid, which was a consequence of the diversion of pyruvate to both lactate and branched-chain amino acid production when S . mutans was cultivated in an acidic environment. Mayo Clin Proc, 2004 May, 79(5), 604 - 12 Changes in the epidemiology of pneumococcal bacteremia in a Swiss university hospital during a 15-year period, 1986-2000; Trampuz A et al.; OBJECTIVE: To evaluate changes in epidemiological characteristics and outcome of patients with pneumococcal bacteremia during a 15-year period in a Swiss university hospital . PATIENTS AND METHODS: We reviewed the medical records of all hospitalized adults at the University Hospital Basel, Basel, Switzerland, whose blood culture yielded Streptococcus pneumoniae from January 1, 1986, through December 31, 2000 . RESULTS: We analyzed 405 episodes of pneumococcal bacteremia in 394 patients . The mean annual incidence of 1.78 episodes per 1000 hospital admissions was inversely related to the mean atmospheric temperature of the area . During the study period, penicillin nonsusceptibility increased from 0% to 17% . The overall case-fatality rate was 25%, which decreased from 33% to 17% between the first and the second half of the study period (P<.001) . The proportion of women with pneumococcal bacteremia increased from 37% to 52% . Independent risk factors for fatal outcome were coronary artery disease (P<.001; relative risk {RR}, 4.3; 95% confidence interval {CI}, 3.4-5.1), neutropenia (P=.001; RR, 3.2; 95% CI, 1.9-4.8), and age 65 years or older (P=.001; RR, 2.9; 95% CI, 1.8-4.2), whereas prior respiratory tract infection (P=.03; RR, 0.3; 95% CI, 0.1-0.5) and the occurrence of pneumococcal bacteremia in the second half of the study period (P=.01; RR, 0.4; 95% CI, 0.2-0.6) were independent predictors of survival . The case-fatality rate in human immunodeficiency virus (HIV)-infected patients was significantly lower than in patients not infected with HIV or in those with unknown HIV status (9% vs 27%; P=.006), which correlated with the younger mean +/- SD age of HIV-infected patients (33.2+/-6.6 years) compared with patients not infected with HIV (63.1+/-18.1 years) (P<.001) . CONCLUSIONS: The case-fatality rate of patients with pneumococcal bacteremia decreased significantly between the first and second half of the study period, despite the increased prevalence of penicillin-nonsusceptible isolates . Independent risk factors for fatal outcome were coronary artery disease, neutropenia, and age 65 years or older, whereas prior respiratory tract infection and the occurrence of pneumococcal bacteremia in the second half of the study period were independent predictors of survival . HIV infection was a predisposing factor for pneumococcal bacteremia but was not a risk factor for fatal outcome. J Clin Microbiol, 2004 May, 42(5), 2345 - 6 Invasive pneumococcal infection in a healthy infant caused by two different serotypes; de Andrade AL et al.; We present a case of invasive pneumococcal infection in a healthy 10-month-old infant from whom Streptococcus pneumoniae serotype 23F was isolated from the blood and serotype 23B was isolated from the cerebrospinal fluid . Both serotypes were penicillin nonsusceptible . Pulsed-field gel electrophoresis analysis demonstrated that the two serotypes had distinct DNA patterns, indicating that infection did not occur as a result of capsular transformation but as a result of a mixed infection with two distinct pneumococcal serotypes. J Clin Microbiol, 2004 May, 42(5), 2161 - 7 Hyperinvasive neonatal group B streptococcus has arisen from a bovine ancestor; Bisharat N et al.; The genetic relatedness and evolutionary relationships between group B streptococcus (GBS) isolates from humans and those from bovines were investigated by phylogenetic analysis of multilocus sequence typing data . The collection of isolates consisted of 111 GBS isolates from cows with mastitis and a diverse global collection of GBS isolates from patients with invasive disease (n = 83) and carriers (n = 69) . Cluster analysis showed that the majority of the bovine isolates (93%) grouped into one phylogenetic cluster . The human isolates showed greater diversity and clustered separately from the bovine population . However, the homogeneous human sequence type 17 (ST-17) complex, known to be significantly associated with invasive neonatal disease, was the only human lineage found to be clustered within the bovine population and was distinct from all the other human lineages . Split decomposition analysis revealed that the human isolate ST-17 complex, the major hyperinvasive neonatal clone, has recently arisen from a bovine lineage. Int J Pediatr Otorhinolaryngol, 2004 Mar, 68(3), 317 - 24 Complications of acute otitis media in children in southern Finland; Leskinen K et al.; BACKGROUND: The incidence of intratemporal and intracranial complications of acute otitis media (AOM) has decreased and the need for operative treatment is declined in developed countries during the antibiotic era . OBJECTIVES: To establish the clinical picture, diagnostic procedures, outcome and current treatment of pediatric patients with intratemporal and intracranial complications of AOM . METHODS: A retrospective chart review with a sent questionnaire . All pediatric patients treated for intratemporal and intracranial complications of AOM over the past 10 years (1990-2000) at the Department of Otolaryngology in the Helsinki University Central Hospital . RESULTS: During the study period 33 children (incidence 1.1/100,000 per year), aged from 3 months to 14.2 years were treated for intratemporal {97% (32/33)} and intracranial {3% (1/33)} complications of AOM . Facial paresis was found in 9% (3/33) of the patients . The only intracranial complication was an extradural abscess with meningitis . Eighteen patients (55%) were on antibiotic treatment because of AOM prior to the diagnosis of complication . Neither the duration or severity of the signs and symptoms of infection at the time of admittance nor a lack of antibiotic treatment before admittance were statistically significantly associated with the need for mastoidectomy or duration of hospitalization . Streptococcus pneumoniae 25% (8/33) and Pseudomonas aeruginosa 22% (7/33) were the most frequently found bacteria in the culture of middle ear and mastoid effusions . Mastoidectomy was performed on 55% (18/33) of the patients . After half a year of follow-up, all the patients had normal hearing and facial function . CONCLUSIONS: Severe complications of AOM are rare today in southern Finland and the need for mastoidectomy has declined significantly . With early recognition and effective treatment of complications, the prognosis is good. J Immunol, 2004 May 15, 172(10), 6324 - 9 Dual role of TLR2 and myeloid differentiation factor 88 in a mouse model of invasive group B streptococcal disease; Mancuso G et al.; Toll-like receptors (TLRs) are involved in pathogen recognition by the innate immune system . Different TLRs and the adaptor molecule myeloid differentiation factor 88 (MyD88) were previously shown to mediate in vitro cell activation induced by group B streptococcus (GBS) . The present study examined the potential in vivo roles of TLR2 and MyD88 during infection with GBS . When pups were infected locally with a low bacterial dose, none of the TLR2- or MyD88-deficient mice, but all of the wild-type ones, were able to prevent systemic spread of GBS from the initial focus . Bacterial burden was higher in MyD88- than in TLR2-deficient mice, indicating a more profound defect of host defense in the former animals . In contrast, a high bacterial dose induced high level bacteremia in both mutant and wild-type mice . Under these conditions, however, TLR2 or MyD88 deficiency significantly protected mice from lethality, concomitantly with decreased circulating levels of TNF-alpha and IL-6 . Administration of anti-TNF-alpha Abs to wild-type mice could mimic the effects of TLR2 or MyD88 deficiency and was detrimental in the low dose model, but protective in the high dose model . In conclusion, these data highlight a dual role of TLR2 and MyD88 in the host defense against GBS sepsis and strongly suggest TNF-alpha as the molecular mediator of bacterial clearance and septic shock. J Immunol, 2004 May 15, 172(10), 6101 - 6 IL-9-induced expansion of B-1b cells restores numbers but not function of B-1 lymphocytes in xid mice; Knoops L et al.; Mice expressing the X-linked immunodeficiency (xid) mutation lack functional Bruton's tyrosine kinase and were shown to be specifically deficient in peritoneal B-1 lymphocytes . We have previously shown that IL-9, a cytokine produced by TH2 lymphocytes, promotes B-1 cell expansion in vivo . To determine whether IL-9 overexpression might compensate the xid mutation for B-1 lymphocyte development, we crossed xid mice with IL-9-transgenic mice . In this model, IL-9 restored normal numbers of mature peritoneal B-1 cells that all belonged to the CD5(-) B-1b subset . Despite this normal B-1 lymphocyte number, IL-9 failed to restore classical functions of B-1 cells, namely, the production of natural IgM Abs, the T15 Id Ab response to phosphorylcholine immunization, and the antipolysaccharide humoral response against Streptococcus pneumoniae . By using bromelain-treated RBC, we showed that the antigenic repertoire of these IL-9-induced B-1b lymphocytes was different from the repertoire of classical CD5(+) B-1a cells, indicating that the lack of B-1 function by B-1b cells is associated with distinct Ag specificities . Taken together, our data show that B-1b cell development can restore the peritoneal B-1 population in xid mice but that these B-1b cells are functionally distinct from CD5(+) B-1a lymphocytes. Fam Pract, 2004 Jun, 21(3), 317 - 23 Acute respiratory symptoms in adults in general practice; Hong CY et al.; BACKGROUND: Community studies have shown that approximately 30% of patients with acute respiratory tract symptoms have no identifiable infective aetiology . This may not be applicable in general practice . OBJECTIVE: The purpose of this study was to determine the infective aetiology in patients who presented to primary care doctors with acute respiratory symptoms . METHODS: A prospective study was carried out in all nine primary care clinics belonging to the National Healthcare Group Polyclinics (NHGPs) in Singapore . The subjects comprised 594 consecutive patients (318 males, 276 females) aged > or = 21 years who presented with complaints of any one of cough, nasal or throat symptoms of <7 days duration . Data collection was through interview using structured questionnaire, physical examination, throat swabs for bacterial culture and nasal swabs for virus identification by immunofluorescence (IF) and polymerase chain reaction (PCR) . Additional PCR was performed on a subsample of 100 patients . Patients were followed-up until resolution of symptoms . RESULTS: The aetiological diagnosis by infective agent is as follows: 150 patients (25.2%) had virus infections, of which 90.7% (136/150) were by rhinovirus . Fourteen patients (2.4%) had bacterial infections, of which 10 were due to group G streptococcus . Group A streptococcus was not detected . Nineteen patients with new pathogens were identified by further PCR . These included parainfluenza 4, human coronavirus OC43, adenovirus, enterovirus and Chlamydia pneumoniae . No pathogen could be identified in 49% of patients . There were no differences in clinical presentation and socio-demographic variables between patients who had viral infections and those in whom no pathogen could be identified . CONCLUSION: In about half of patients who presented at NHGPs, no pathogens could be identified even after PCR . A non-infective aetiology could be considered in these patients. Clin Infect Dis, 2004 May 15, 38 Suppl 4, S363 - 71 Antibiotic resistance in Streptococcus pneumoniae: what does the future hold? Nuermberger EL, Bishai WR. The recent emergence of strains of drug-resistant Streptococcus pneumoniae (DRSP) is a serious clinical and public health problem . Several interventions have been proposed to limit the further emergence and spread of DRSP, including campaigns for appropriate antibiotic use and the introduction of pneumococcal conjugate vaccines . Whether the current epidemic of drug resistance in S . pneumoniae is sustainable or will succumb to current efforts to limit its spread will be decided by an interaction of factors related to the pathogen (i.e., the relative fitness of the resistant strains), to the prescription of antibiotic treatment (i.e., changes in selection pressure), and to the host (i.e., the ability to slow the transmission of DRSP) . Much investigation is still needed to better ascertain how maintenance of DRSP strains in the community at large is influenced by each factor and affected by current interventions that are based on these factors. Clin Infect Dis, 2004 May 15, 38 Suppl 4, S357 - 62 Quinolone resistance among pneumococci: therapeutic and diagnostic implications; Low DE; Fluoroquinolones are widely recommended as empirical monotherapy for community-acquired pneumonia . Since 1999, case reports of failure of levofloxacin therapy due to levofloxacin-resistant strains of Streptococcus pneumoniae have started to appear . Most worrying is that, in some cases, levofloxacin resistance has been acquired by pneumococci within days of the initiation of therapy . Because use of current clinical antimicrobial resistance breakpoints fail to identify the majority of S . pneumoniae isolates with only first-step mutations, current treatment guidelines not only may have implications with regard to the ability of surveillance programs to detect emerging resistance but may have therapeutic implications as well. Clin Infect Dis, 2004 May 15, 38 Suppl 4, S350 - 6 Quinolone resistance mechanisms in pneumococci; Eliopoulos GM; Quinolones are widely used in the treatment of respiratory infections, in large part because of their activity against Streptococcus pneumoniae and other commonly encountered respiratory tract pathogens . Pneumococcal isolates that are resistant to these "respiratory quinolones" have now begun to emerge . Resistance is attributable to mutations affecting the intracellular targets of these drugs, topoisomerase IV and DNA gyrase; drug efflux contributes to quinolone resistance in some isolates . Most commonly, strains fully resistant to the newer quinolones have one or more mutations affecting DNA gyrase and topoisomerase IV . Although various agents of this class exhibit selectivity in primarily targeting one or the other of these enzymes, the passage of isolates in the presence of any agent can result in selection of mutations affecting both enzymes . Quinolone resistance in S . pneumoniae has arisen in heterogeneous genetic backgrounds but, ominously, has now appeared in strains that are well adapted for regional and global transmission. Clin Infect Dis, 2004 May 15, 38 Suppl 4, S346 - 9 Penicillin and macrolide resistance in pneumococcal pneumonia: does in vitro resistance affect clinical outcomes? Rothermel CD. In vitro resistance to antimicrobial agents is escalating among pathogens responsible for the most serious respiratory tract infections . Some reports have suggested that this has direct clinical implications . Because of penicillin and macrolide resistance in Streptococcus pneumoniae, current guidelines for the initial treatment of respiratory tract infections advocate less reliance on the use of either of these classes of drugs in single-agent therapy . Recent studies that have assessed the impact of beta -lactam and macrolide resistance on clinical outcomes in community-acquired pneumonia fail to provide incontrovertible evidence for a direct link between in vitro resistance and treatment failure . However, there are anecdotal reports of breakthrough bacteremia due to macrolide-resistant pneumococci among patients receiving macrolide therapy, unlike the situation for beta -lactams and penicillin-resistant pneumococci . Continued efforts, including in vitro surveillance, appropriate antibiotic use campaigns, and immunization programs, will be important in limiting the spread of drug-resistant S . pneumoniae. Clin Infect Dis, 2004 May 15, 38 Suppl 4, S322 - 7 Pneumococcal resistance to macrolides, lincosamides, ketolides, and streptogramin B agents: molecular mechanisms and resistance phenotypes; Edelstein PH; The macrolides, lincosamides, ketolides, and streptogramin B agents (the MLKS(B) antimicrobial agents) have related chemical structures and share similar molecular targets on the 50S ribosomal subunit of Streptococcus pneumoniae . Mutations in rRNA or ribosomal proteins generate a variety of resistance phenotypes . The M phenotype of S . pneumoniae, which predominates in North America, affords low-level resistance to macrolides only (excluding macrolides with 16-member rings) by means of an efflux pump encoded by the mefA gene . The MLS(B) phenotype, which predominates in Europe, affords high-level resistance to macrolides, lincosamides, and streptogramin B agents and arises, in most cases, from dimethylation of adenine 2058 in the 23S rRNA of the 50S ribosomal subunit . Other, less common, phenotypes arise from other 23S rRNA modifications (ML and K phenotypes) or from amino acid substitution (MS(B) phenotype) or insertion (MKS(B) phenotype) into the 50S subunit ribosomal protein L4 . In all cases, the decrease in susceptibility to ketolides (for example, telithromycin) is less than the decrease in susceptibility for other MLKS(B) agents. Clin Infect Dis, 2004 May 1, 38(9), 1273 - 8 Epub 2004 Apr 14. Pneumococcal endocarditis in children; Givner LB et al.; Endocarditis due to Streptococcus pneumoniae is unusual in children, accounting for 3%-7% of all cases of childhood endocarditis . The US Pediatric Multicenter Pneumococcal Surveillance Group has prospectively identified patients with invasive disease at 8 children's hospitals . During the period of 1 September 1993 through 28 February 2003, a total of 11 children with pneumococcal endocarditis were seen . Seven (64%) were 3-36 months old; 8 (73%) were boys . Ten (91%) had preexisting structural heart disease; 5 had undergone previous heart surgery . Concomitant sites of infection were noted in 6 patients (55%), including 3 patients with meningitis . One patient (9%) died during hospitalization, and 5 others (45%) experienced serious complications . Only 2 patients remained hospitalized for their entire course of parenteral antibiotic therapy . Eight of 10 pneumococcal isolates tested were vaccine or vaccine-related serotypes included in the currently licensed 7-valent conjugated pneumococcal vaccine . Pneumococcal endocarditis in children is unusual but often has serious complications. Clin Infect Dis, 2004 May 1, 38(9), 1251 - 6 Epub 2004 Apr 14. Effect of macrolide consumption on erythromycin resistance in Streptococcus pyogenes in Finland in 1997-2001; Bergman M et al.; The aim of this study was to investigate the association between regional macrolide resistance in Streptococcus pyogenes and macrolide use in Finland . During 1997-2001, a total of 50,875 S . pyogenes isolates were tested for erythromycin susceptibility in clinical microbiology laboratories throughout Finland . The local erythromycin resistance levels were compared with the regional consumption data of all macrolides pooled and, separately, with the use of azithromycin . The regional resistance rates of 1 year were compared with the regional consumption of the previous year and with the average rates of use for the 2 previous years . A linear mixed model for repeated measures was used in modeling the association . A statistically significant association existed between regional erythromycin resistance in S . pyogenes and consumption of macrolides; association with azithromycin use alone was not found. J Bacteriol, 2004 May, 186(10), 3078 - 85 Two separate quorum-sensing systems upregulate transcription of the same ABC transporter in Streptococcus pneumoniae; Knutsen E et al.; Streptococcus pneumoniae secretes two different peptide pheromones used for intercellular communication . These peptides, which have completely unrelated primary structures, activate two separate signal transduction pathways, ComABCDE and BlpABCSRH, which regulate natural genetic transformation and bacteriocin production, respectively . Each signal transduction pathway contains a response regulator (ComE and BlpR, respectively) that activates transcription of target genes by binding to similar, but not identical, imperfect direct repeat motifs . In general the direct repeat binding sites are specific for one or the other of the two response regulators, ensuring that competence development and bacteriocin production are regulated separately . However, in the present study we show that the rate of transcription of an operon, encoding an ABC transporter of unknown function, can be stimulated by both peptide pheromones . We also show that this cross-induction is due to a hybrid direct repeat motif that can respond to both ComE and BlpR . To our knowledge this kind of convergent gene regulation by two separate two-component regulatory systems has not been described before in bacteria. Int J Pediatr Otorhinolaryngol, 2004 Jun, 68(6), 759 - 65 Bacteriology of medically refractory acute otitis media in children: a 9-year retrospective study; Shiao AS et al.; OBJECTIVE: To identify the causative organisms for medically refractory acute otitis media (AOM) in children, and to recommend the appropriate antibiotics for these patients . STUDY DESIGN: Retrospective chart review . METHODS: The medical records for 671 children (1258 ears) undergoing myringotomies between January 1993 and December 2001 were retrospectively reviewed . "Medically refractory" AOM is defined as AOM requiring emergency myringotomy because of toxicity persisting despite second-phase antibiotics . Of these, 18 children were enrolled in our study, with 25 of the ears affected by medically refractory AOM . Myringotomy was performed for pus drainage, bacterial culture and susceptibility studies in all cases . Clinical factors were analyzed to demonstrate possible relationships with microbiological findings . RESULTS: Bacteria were recovered in specimens taken from 12 ears . The positive culture rate was 48% . Bacteriological studies showed mostly growing gram-positive bacteria, such as coagulase negative staphylococcus, Staphylococcus aureus and Streptococcus pneumoniae (in decreasing order of incidence) . The sensitivity rate to pre-myringotomy antibiotics was 85.7% . With the exception of Pseudomonas aeruginosa and two ears with intracranial complications or pneumonia, all other isolated microorganisms were susceptible to first-generation cephalosporins . No statistically significant differences were noted between culture rates and clinical factors . CONCLUSION: The distribution of organisms in our medically refractory AOM cases differed from that for simple AOM, with gram-positive bacteria having significantly higher rates of incidence . Combining intravenous aminoglycoside with first-generation cephalosporin is considered an inexpensive and effective treatment covering all potential microorganisms . Vancomycin or third-generation cephalosporins are only needed for major complications or other coincident infections extant during the initial presentation. J Clin Epidemiol, 2004 Feb, 57(2), 142 - 6 Pharyngitis clinical prediction rules: effect of interobserver agreement: a MetroNet study; Schwartz K et al.; OBJECTIVE: Pharyngitis clinical prediction rules improve Group A beta-hemolytic streptococcus (GABHS) diagnosis and decrease unnecessary antibiotic use, yet few studies have addressed clinician variability in assessment of sore throat signs and symptoms . STUDY DESIGN AND SETTING: We conducted a cross-sectional study in which two clinicians examined each of 200 adult sore throat patients . Each patient had a rapid GABHS antigen test . Clinicians were blinded to each other's assessment and to the rapid antigen result . Interobserver agreement was estimated using a kappa coefficient . Effect of agreement on sensitivity, specificity, and hypothetic rapid antigen testing and antibiotic prescribing was determined for two clinical prediction rules . RESULTS: We found moderate inter-rater reliability on sore throat history and physical assessments . Clinician agreement was associated with significantly fewer hypothetic rapid antigen tests performed . CONCLUSION: Interobserver agreement enhances the utility of pharyngitis clinical prediction rules . Medical school and residency training should focus on correct assessment of history and physical examination components used in GABHS clinical prediction rules . Correct assessment will result in less GABHS testing and antibiotic prescriptions for sore throat patients. Gynecol Obstet Fertil, 2004 Feb, 32(2), 135 - 9 {Abnormal bacterial colonisation of the vagina and implantation during assisted reproduction}; Wittemer C et al.; OBJECTIVE: To evaluate the efficiency of our treatment of vaginal infection for couples included in an IVF program . PATIENTS AND METHODS: Microbiologic screening of vaginal flora and semen has been performed one month prior to in vitro fertilization for 951 couples in 2000 . Antibiotic treatment was prescribed in case of positive culture . RESULTS: Positive microbial growths were observed from endocervical and vaginal cultures in 218 women (22.9%) . The clinical pregnancy rate was 30.29% in the group of patients without growth and 30.27% in the group with positive microbial growth . The implantation rate was significantly diminished in case of bacterial growth: 14.6 compared to 19.3% (P <0.02) for sterile endocervical culture . Five main bacterial species were found at the cervical level: Candida albicans (69 cases), Ureaplasma urealyticum (49 cases), Gardnerella vaginalis (43 cases), Streptococcus B or D (24 cases) and Escherichia coli (22 cases) . Positive cultures from both vagina and semen were observed for 77 couples whose clinical pregnancy rate was 19.5 vs 36.2% in case of vaginal infection alone (P <0.01) with a spontaneous miscarriage rate of 46.7 compared to 17.6% (P <0.01) . DISCUSSION AND CONCLUSION: Endocervical microorganisms, even treated with adapted antibiotics, may affect embryonic implantation . Positive culture from both female and male partner may enhance this negative effect . In this case, the best strategy would be to cancel the IVF treatment. J Infect Dis, 2004 May 15, 189(10), 1905 - 13 Epub 2004 Apr 27. The effect that mutations in the conserved capsular polysaccharide biosynthesis genes cpsA, cpsB, and cpsD have on virulence of Streptococcus pneumoniae; Morona JK et al.; Four genes, cpsA-cpsD, at the 5' end of the capsular polysaccharide (CPS) biosynthesis locus are conserved in nearly all of the 90 known serotypes of Streptococcus pneumoniae . In the present study, the impact that mutations in cpsA, cpsB, and cpsD have on CPS production and on virulence in mice infected via systemic and intranasal routes was investigated . Strains exhibiting rough colony morphologies (in which either the cpsB or cpsD gene had been deleted) were avirulent, but a smooth, partially encapsulated strain (in which the cpsA gene had been deleted) was as virulent as the wild-type strain . Interestingly, mucoid strains containing mutations affecting the {YGX}(3)-repeat domain of CpsD were unable to cause bacteremia after intranasal challenge of CD1 mice, even though such strains were capable of killing BALB/c mice after intraperitoneal challenge . In our model, the ability of S . pneumoniae to regulate, via CpsD phosphorylation, CPS production was required for its transition from the lung to the bloodstream. J Am Soc Echocardiogr, 2004 May, 17(5), 474 - 7 Echocardiographic features of an unruptured mycotic aneurysm of the right aortic sinus of Valsalva; Batiste C et al.; This report describes a 25-year-old man with a pierced tongue in whom Streptococcus constellatus endocarditis of the aortic valve developed . Bacterial endocarditis in this patient was complicated by the development of a mycotic aneurysm of the right aortic sinus of Valsalva . Transthoracic and transesophageal echocardiographic studies were useful for the diagnosis of this rare lesion . Findings were confirmed at operation. J Lab Clin Med, 2004 May, 143(5), 269 - 83 Clinical relevance of antimicrobial resistance in the management of pneumococcal community-acquired pneumonia; Feldman C; Streptococcus pneumoniae remains the most common bacterial cause of community-acquired pneumonia, and these infections are associated with significant morbidity and mortality worldwide . A major concern is the increasing incidence of antibiotic resistance among pneumococcal isolates, which, in the case of certain of the antibiotic classes, has been associated with treatment failure . Yet despite multiple reports of infections with penicillin-resistant pneumococcal isolates, no cases of bacteriologic failure have been documented with the use of penicillin or ampicillin in the treatment of pneumonia caused by penicillin-resistant pneumococci . Current prevalence and levels of penicillin resistance among pneumococal isolates in most areas of the world do not indicate a need for substantial treatment changes with regard to the use of the penicillins . For infections with penicillin-sensitive strains, penicillin or an aminopenicillin in a standard dosage will still be effective for treatment . In the cases of strains with intermediate resistance, beta-lactam agents are still considered appropriate treatment, although higher dosages are recommended . Infections with isolates of high-level penicillin resistance should be treated with alternative agents such as the third-generation cephalosporins or the new antipneumococcal fluoroquinolones . In the case of the cephalosporins, pharmacodynamic/pharmacokinetic parameters help predict which of those agents are likely to be successful, and the less active agents should not be used . Debate continues in the literature with regard to the impact of macrolide resistance on the outcome of pneumococcal pneumonia, with some investigators providing evidence of an "in vivo-in vitro paradox," referring to discordance between reported in vitro resistance and clinical success of macrolides/azalide in vivo . However, several cases of macrolide/azalide treatment failure have been documented, and many clinicians recommend that these agents not be used on their own in areas with a high prevalence and levels of macrolide/azalide resistance . However, evidence is emerging to show beneficial effects on outcome with combination therapy, especially that of a beta-lactam agent and a macrolide given together to sicker, hospitalized patients with pneumococcal pneumonia . In an attempt to prevent the emergence of resistance, it has been recommended by some that the new fluoroquinolones not be used routinely as first-line agents in the treatment of community-acquired pneumonia; instead, they say, these agents should be reserved for patients who are allergic to the commonly used beta-lactam agents, for infections known to be or suspected of being caused by highly resistant strains, and for patients in whom initial therapy has failed. Int J Antimicrob Agents, 2004 May, 23(5), 517 - 9 Susceptibility of Streptococcus pyogenes to two macrolides in northern Israel; Sakran W et al.; In the present study, the minimal inhibitory concentration (MIC) of azithromycin and roxithromycin for 200 Streptococcus pyogenes isolates from outpatients with tonsillopharyngitis were determined using Etest . All but one (99.5%) of the isolates were sensitive to both antibiotics; the MIC of the resistant isolate being 12 mg/l to azithromycin and 32 mg/l to roxithromycin . In this region, macrolides remain the drug of choice for the treatment of patients with S . pyogenes tonsillitis who present allergy to penicillin . The routine testing of susceptibility of S . pyogenes to macrolides in northern Israel is not justified. Int J Antimicrob Agents, 2004 May, 23(5), 498 - 501 Efficacy of clarithromycin against Streptococcus pneumoniae expressing mef(A)-mediated resistance; Maglio D et al.; As a result of macrolide resistance rates of 25% for pneumococci in the US, the clinical use of this class as empirical therapy has been questioned . However, macrolides continue to be used with clinical success . Using an immunocompromised murine pneumonia model, this study evaluated in vivo efficacy of human simulated exposures of clarithromycin for 62 isolates of Streptococcus pneumoniae considered resistant by current methods of breakpoint determinations . Changes in bacterial density were compared between treated animals and untreated controls . Inhibition of bacterial growth was consistently observed for the majority of isolates tested with mean (S.D.) reductions in logCFU per lung of -0.88 (0.69), -1.02 (0.87), -0.47 (0.79), -0.84 (0.66), -0.25 (0.26), -0.80 (0.72) and -0.58 (0.47) for MICs of 1, 2, 4, 8, 16, 32 and 64 mg/l, respectively . A beneficial treatment effect was clearly noted for isolates with clarithromycin MICs <==8 mg/l . However, the sample size of isolates tested beyond the MIC of 8 mg/l was diminished due to mortality in both treated and untreated animals . Consistent suppression of bacterial growth observed in this neutropenic model provides support for the in vivo efficacy of clarithromycin with low-level macrolide-resistant S . pneumoniae. Microb Pathog, 2004 Jun, 36(6), 327 - 35 Identification and characterisation of hyaluronate lyase from Streptococcus suis; Allen AG et al.; Hyaluronate lyase, which catalyses the degradation of hyaluronic acid (HA), has been described from several pathogenic streptococcal species . We describe, for the first time, identification and purification of hyaluronate lyase from the zoonotic pig pathogen Streptococcus suis . We have cloned the hyaluronate lyase gene from S . suis and used it to generate an allelic replacement knock-out mutant of S . suis serotype 7 that can no longer biosynthesise the enzyme . Interestingly, a limited strain survey indicates that hyaluronate lyase activity is not present in all disease isolates of S . suis . Polyclonal anti-hyaluronate lyase anti-serum raised against our recombinant hyaluronate lyase has been used in Western blots, showing that hyaluronate lyase activity is always associated with the presence of protein of the expected size, whereas lack of hyaluronate lyase activity is due to truncation or absence of the enzyme . We show that hyaluronate lyase activity is required for S . suis to use HA polymer as a carbon source and that supplying exogenous recombinant hyaluronate lyase to all S . suis strains tested allowed fermentation of the resultant HA breakdown products. Microb Pathog, 2004 Jun, 36(6), 303 - 10 Nitric oxide exerts distinct effects in local and systemic infections with Streptococcus pneumoniae; Kerr AR et al.; Nitric oxide (NO) is known to be involved in the immune response against a range of organisms . Little is known about the effects of nitric oxide in pneumococcal infections . We have now investigated the role of nitric oxide in local and systemic infections caused by Streptococcus pneumoniae in NOS2 deficient mice . Although a deficiency in NO does not affect survival of mice during pneumococcal pneumonia, NO does control pneumococcal viability within the lung airways and tissue . Bronchoalveolar lavage fluid (BALF) from NOS2-deficient mice contained significantly elevated TNF activity, IFNgamma and total protein during mid/late infection . Incubation of S . pneumoniae with the NO donor SNAP revealed a direct anti-pneumococcal effect for NO in vitro . Deficiency in NOS2 did not affect bacteraemia following intranasal infection . In contrast NOS2-deficient mice were significantly less susceptible to intravenous infection with S . pneumoniae than were wild type mice and were able to control pneumococcal viability within the bloodstream . Our results indicate that NO is required within the lungs for anti-bacterial activity during the pneumococcal pneumonia but during Gram-positive bacteraemia NO is associated with increased bacterial loads and reduced survival. Quintessence Int, 2004 Apr, 35(4), 275 - 9 Antibacterial surface properties of polymerized single-bottle bonding agents: part II; Slutzky H et al.; OBJECTIVE: Microorganisms are directly associated with the etiology of enamel, dentin, and pulpal pathology . Due to the growing usage of one-bottle bonding materials with resin composite restorations, as well as sealing agents with amalgam restorations, it is important that they possess antibacterial properties . In the present study, the antibacterial properties of polymerized one-bottle bonding agents were tested, using the direct contact test (DCT) and the agar diffusion test (ADT) . METHOD AND MATERIALS: Quadruple samples of the following materials were tested in both assays: Bond-1, OptiBond Solo, One-Step, Gluma, Prime & Bond NT, and Synergy . In the DCT, samples were placed on the sidewalls of wells of a 96-microtiter plate and polymerized . A 10-microL suspension of Streptococcus mutans was placed on the surface of each sample for 1 hour at 37 degrees C . Fresh media was then added, and bacterial growth was followed with a temperature-controlled spectrophotometer . In the ADT, samples were placed in punched wells of inoculated agar plates, and halos in the bacterial lawn were measured after 72 hours . RESULTS: In the DCT, all the tested bonding agents exhibited potent antibacterial properties; virtually no viable bacteria were present in any of the samples . When the samples were aged in phosphate-buffered saline for 24 hours, all the tested agents, similar to the freshly polymerized samples, exhibited potent antibacterial properties . This property was lost in samples aged for 7 days . Fresh samples assayed by ADT demonstrated no inhibition halo around any of the samples . CONCLUSION: Collectively, the present data suggest that one-bottle bonding agents possess in vitro antibacterial properties for at least 24 hours . This phenomenon was demonstrated only by DCT. Quintessence Int, 2004 Mar, 35(3), 200 - 5 Histologic evaluation of adhesive restorations on dentin caries in rat molar teeth; Shimada Y et al.; OBJECTIVE: The aim of this study was to evaluate the progress of dentin caries under resin composite and glass-ionomer cement restorations in vivo . METHOD AND MATERIALS: Sixteen rats were subjected to oral inoculation of the bacterial strain, Streptococcus mutans, and experimental dental caries was induced in the rats' molars . The dental caries induced in rat molars was sealed with resin composite or glass-ionomer cement without removal of the caries; the depth and width of bacterial penetration in the lesion were measured from histopathologically stained sections . Inflammatory cell infiltrations within the pulp were also examined . RESULTS: Both bacterial penetration into dentin and caries spread were significantly reduced by sealing with glass-ionomer cement or resin composite . No significant differences in bacterial penetration and caries spread were seen between the sealing materials . Regarding the pulpal reactions, moderate to severe inflammatory cell infiltration was observed even in the sealed teeth . CONCLUSION: The caries lesions could not be completely arrested by sealing alone, although their progress was slowed from an active to a chronic status. Eur J Pediatr, 2004 Jul, 163(7), 364 - 8 Epub 2004 Apr 30. Serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae causing invasive infections and acute otitis media in children; Zissis NP et al.; A prospective study was conducted to determine the serotypes and antibiotic resistance patterns of pneumococcal isolates from children with invasive pneumococcal disease (IPD) and acute otitis media (AOM) . From October 2001 to May 2002, 65 children with IPD (28 bacteraemic pneumonia, 24 bacteraemia without focus, 7 meningitis, 6 other infections) and 78 with AOM were identified . The most common serotypes causing IPD were 14 (32.3%), 6B (20.0%), 1 (18.5%) and 19F (7.7%) whereas the predominant serotypes causing AOM were 19F (35.9%), 14 (16.7%) and 23F (9.1%) . Sixty-nine percent of IPD and 70.5% of AOM were caused by vaccine serotypes . The vaccine serotypes were more commonly encountered in meningitis cases and in children younger than 2 years of age . Intermediate resistance to penicillin was observed in 6 of 65 (9.2%) IPD isolates, one of which was intermediately resistant to cefotaxime (1.6%), whereas none exhibited high-level resistance to penicillin or other beta-lactam antibiotics . A higher proportion of antimicrobial resistance was noted in AOM isolates; 29 of 78 (37.4%) exhibited intermediate resistance and 8 (10.2%) high level resistance to penicillin, four of which had intermediate resistance to cefotaxime . Significant resistance was also noted to erythromycin; 38.5% of IPD and 48.7% of AOM isolates were resistant . Multidrug resistance was observed in one IPD and in eight AOM isolates . CONCLUSION: these findings have implications in the potential use of 7-valent conjugate vaccine in our region . J Antimicrob Chemother, 2004 Jun, 53(6), 918 - 27 Epub 2004 Apr 29. Clinical efficacy of ketolides in the treatment of respiratory tract infections; Reinert RR; Ketolides are a new class of semi-synthetic agents derived from erythromycin A designed to overcome erythromycin A resistance in Streptococcus pneumoniae . Telithromycin (HMR 3647) is the first member of this new class to be approved for clinical use . Cethromycin (ABT-773) has been developed up to Phase III, but its further development seems questionable at the moment . Other ketolides are only in the first stages of preclinical development and may not be available within the foreseeable future . Ketolide compounds inhibit bacterial protein synthesis by interacting with the peptidyl transferase site of the 50S ribosomal subunit, and interact closely with domains II at A752 and V at A2058 and A2059 of the 23S rRNA . These compounds also inhibit the formation of the 50S subunit of the ribosome . Ketolides show good activity against the Gram-positive bacteria responsible for respiratory tract infections including penicillin G- and erythromycin A-resistant S . pneumoniae . The 15 clinical trials with telithromycin published to date include four randomized, double-blind comparative trials and three open-label studies in community-acquired pneumonia, three randomized double-blind trials in acute exacerbation of chronic bronchitis, two randomized double-blind trials in pharyngitis, and two double-blind comparative trials and one open-label trial in acute maxillary sinusitis . Clinical response rates were favourable in all clinical trials, with eradication rates in patients with pneumococcal bacteraemia and penicillin G- and erythromycin A-resistant pneumococcal infections at least as high as those of comparators . As resistance to macrolides continues to emerge, the availability of other ketolides besides telithromycin and a development programme for the application of ketolides in children would appear to be warranted to obtain a new class of antibiotics that may one day replace macrolides. J Ocul Pharmacol Ther, 2004 Apr, 20(2), 123 - 8 Sterility of glaucoma medications among chronic users in the community; Porges Y et al.; PURPOSE: To evaluate the sterility of topical glaucoma medications among chronic glaucoma medication users in the community . SETTING: Glaucoma service, Sanz Medical Center, Laniado Hospital, Netanya . Research mode: Cross-sectional laboratory and clinical study . PATIENTS AND METHODS: Chronic glaucoma patients were asked to submit their topical glaucoma preparations to the microbiology laboratory at Laniado hospital . Samples taken from the interior of the bottle and the tip were cultured using MacConkey agar, blood agar, and chocolate agar plates . RESULTS: Sixty-two bottles of topical glaucoma medications used by 27 patients were tested . Bacterial growth was detected in eight (12.9%) preparations, three of which revealed Pseudomonas aeruginosa, three Staphylococcus epidermidis, one Streptococcus viridans, and one Klebsiella . During the study, acute conjunctivitis was found in one patient, possibly due to the use of infected drops . In another case, two identical medications, which had been used simultaneously for more than 6 weeks by the same patient, were found to be infected . CONCLUSIONS: Glaucoma topical preparations are generally found safe in terms of sterility, though bacterial growth may be found in a small percentage . In most cases, the cause of the loss of sterility could not be determined . However, in two preparations, contamination was related to the noncompliance of the patient who continued using the same preparation longer than instructed . It is imperative to increase the awareness of glaucoma patients to the fact that improper use can lead to eye-drop contamination. Int J Dermatol, 2004 May, 43(5), 341 - 7 IgG class antibodies from psoriasis patients recognize the 60-KDa heat-shock protein of Streptococcus pyogenes; Cancino-Diaz ME et al.; BACKGROUND: We have previously found that psoriatic patients have IgG autoantibodies that recognize lesions but not autologous normal skin . The reactivity of the autoantibodies can be adsorbed with streptococcal antigens . METHODS: IgG antibodies were determined by immunoblot and ELISA to streptococcal antigens and by ELISA to the recombinants HSP60Sp, HSP70Sp, HSP60Ec and HSP60Hu, in plaque (PP) and guttate (GP) psoriasis patients, in healthy subjects (HC) and in individuals with streptococcal throat infections and high ASO titers, but without history of dermatological disease (ISp) . RESULTS: We found by immunoblot that the IgG response to 71-, 60-, and 14-kDa protein fractions of Streptococcus pyogenes is important in psoriasis . We also found by ELISA that the response to the rHSP60Sp in PP was higher than in all the other three groups studied (P < 0.05) with an odds ratio of 11.11 (CI95% of 4.33-28.49) . The PP infected with S . pyogenes had higher titers of the antirHSP60Sp, high ASO, and high PASI . The PP patients did not significantly recognize the HSP60Ec or the HSP60Hu . The GP patients had a higher response to the rHSP60Sp than the healthy controls or ISp patients (P < 0.05) but showed no association with the disease . The response of the ISp patients to the HSP60Sp was similar to the healthy controls . The response to the rHSP70Sp was similar in the PP patients and the healthy controls . CONCLUSION: Results suggest that a high response to the HSP60Sp could be associated with the chronic form of psoriasis. Brain, 2004 Jun, 127(Pt 6), 1437 - 45 Epub 2004 Apr 28. MyD88 is required for mounting a robust host immune response to Streptococcus pneumoniae in the CNS; Koedel U et al.; Myeloid differentiation factor 88 (MyD88) is an essential intracellular signal transducer in Toll-like receptor (TLR) and interleukin (IL)-1 receptor family member-mediated cell activation . In order to characterize the role of MyD88 in pneumococcal meningitis we used gene-targeted mice lacking functional MyD88 expression . At 24 h after intracisternal infection, MyD88- deficient mice displayed a markedly diminished inflammatory host response in the CNS, as evidenced by reduced CSF pleocytosis and expression of cytokines, chemokines and complement factors . The reduced CNS inflammation was paralleled by a marked reduction in the prognostic relevant CNS complications, such as brain oedema formation . Nevertheless, MyD88 deficiency was associated with a worsening of disease which seemed to be attributable to severe bacteraemia . This notion was supported by the unexpected observation that infected MyD88-deficient mice displayed enhanced mRNA expression of inflammatory mediators {such as the proinflammatory cytokine tumour necrosis factor alpha (TNF-alpha) and the CXC chemokine macrophage inflammatory protein (MIP-2)} in the lung and consequently increased cell influx in the bronchoalveolar lavage fluid, compared with infected wild-type mice . Thus, the present study demonstrated for the first time an important role of MyD88 in immune activation to bacterial pathogens within the CNS . The role played by MyD88 in mounting an immune response to Streptococcus pneumoniae, however, seems to be dependent on the anatomical compartment involved. J Med Chem, 2004 May 6, 47(10), 2409 - 10 Synthesis and evaluation of oxazaborolidines for antibacterial activity against Streptococcus mutans; Jabbour A et al.; Several representative oxazaborolidines have been synthesized and evaluated against S . mutans for antibacterial activity . This is the first reported antibacterial activity of this class of compounds . The minimal inhibitory concentration values ranged from 0.53 to 6.75 mM. Dig Liver Dis, 2004 Apr, 36(4), 296 - 300 Sepsis and elevated liver enzymes in a patient with inflammatory bowel disease: think of portal vein thrombosis; Mijnhout GS et al.; A 42-year old man, 1 year previously diagnosed with ulcerative colitis after an emergency subtotal colectomy with formation of an ileostomy because of severe colitis with perforation, was admitted with sepsis and jaundice . The liver enzymes were elevated and blood cultures were positive for Streptococcus milleri . Magnetic resonance imaging showed a complete thrombosis of the main stem of the portal vein with occlusion of the left branch . Intravenous antibiotic therapy combined with heparinisation led to complete recanalisation of the thrombus . Portal vein thrombosis is a rare complication of inflammatory bowel disease and has been described in only 10 patients thus far . Multiple aetiologic factors may be responsible in relation to inflammatory bowel disease, such as hypercoagulability, thrombocytosis and abdominal sepsis . In patients with inflammatory bowel disease, unexplained sepsis and abnormal liver function tests, the possibility of an acute portal vein thrombosis should be considered and investigated, because unrecognised it may have serious long-term complications. Histochem Cell Biol, 2004 May, 121(5), 383 - 90 Epub 2004 Apr 28. Expression of integrin subunits alphav and beta3 in acute lung inflammation; Janardhan KS et al.; Integrin subunits alphav and beta3 form a dimer, alphavbeta3, which is expressed on normal neutrophils and endothelium . We investigated the expression of integrin subunits alphav and beta3 in acute lung inflammation in Sprague-Dawley rats ( n=5 each) following intratracheal challenge with Escherichia coli or Streptococcus pneumoniae, which induce neutrophil recruitment through different mechanisms . Control rats ( n=5) were given endotoxin-free saline . Both bacterial challenges induced similar levels of recruitment of neutrophils in lungs . Western blots showed lower expression of integrin subunits alphav and beta3 in lungs challenged with E . coli compared to those given S . pneumoniae . Immunohistochemistry and immunogold electron microscopy localized both integrin subunits in neutrophils and endothelium in the control and treated rat lungs . Quantitative immunohistochemistry showed that E . coli-challenged rat lungs contained a lower percentage of neutrophils expressing integrin subunits alphav and beta3 compared to those challenged with S . pneumoniae ( P<0.05) . We conclude that E . coli infection decreased the percentage of neutrophils expressing integrin subunits alphav and beta3 compared to S . pneumoniae infection . These data lay the foundation for further characterization of these integrin subunits in neutrophil migration specifically in S . pneumoniae infection that utilizes molecules other than beta2 integrins for neutrophil recruitment. J Chromatogr B Analyt Technol Biomed Life Sci, 2004 Jun 5, 805(1), 155 - 60 Purification of glucosyltransferase from cell-lysate of Streptococcus mutans by counter-current chromatography using aqueous polymer two-phase system; Yanagida A et al.; Counter-current chromatography (CCC) using a cross-axis coil planet centrifuge (X-axis CPC) was applied to the purification of glucosyltransferase (GTF) from a cell-lysate of cariogenic bacteria . The purification was performed using an aqueous polymer two-phase system composed of 4.4% (w/w) polyethylene glycol (PEG) 8000-6% (w/w) dextran T500 containing 10mM phosphate buffer at pH 9.2 by eluting the upper phase (UP) at 1.0ml/min . The bacterial GTF in the cell-lysate of Streptococcus mutans was selectively retained in the dextran-rich lower stationary phase . The column contents were diluted and subjected to hydroxyapatite (HA) chromatography to remove the polymers from the GTF . Fractions eluted with 500mM potassium phosphate buffer were analyzed by GTF enzymatic activity as well as sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) . The GTF purity in the final product was increased about 87 times as that in the cell-lysate with a good recovery rate of about 79% through this purification process. Clin Microbiol Infect, 2004 May, 10(5), 409 - 15 The plasma level of soluble urokinase receptor is elevated in patients with Streptococcus pneumoniae bacteraemia and predicts mortality; Wittenhagen P et al.; This multicentre prospective study was conducted to investigate whether the level of the soluble form of urokinase-type plasminogen activator receptor (suPAR) is elevated during pneumococcal bacteraemia and is of predictive value in the early stage of the disease . Plasma levels of suPAR were increased significantly (median 5.5; range 2.4-21.0 ng/mL) in 141 patients with pneumococcal bacteraemia, compared to 31 healthy controls (median 2.6, range 1.5-4.0 ng/mL, p 0.001) . Furthermore, suPAR levels were elevated significantly in patients who died from the infection (n = 24) compared to survivors (n = 117; p < 0.001) . No correlation was found between suPAR levels and C-reactive protein . In univariate logistic regression analysis, hypotension, renal failure, cerebral symptoms and high serum concentrations of protein YKL-40 and suPAR were associated significantly with mortality (p < 0.05) . In multivariate analysis, only suPAR remained a significant predictor of death (mortality rate of 13 for suPAR levels of > 10 ng/mL; 95% CI: 1.1-158) . The increase in suPAR levels may reflect increased expression by vascular or inflammatory cells in the setting of pneumococcal sepsis . This plasma protein may be used to identify patients who are severely ill with pneumococcal bacteraemia. Ceska Gynekol, 2004 Jan, 69(1), 7 - 14 {Microbiological findings in patients with recurrent vulvovaginal candidiasis in the Hradec Králové Faculty Hospital 1995-2002}; Buchta V et al.; OBJECTIVE: To evaluate the microbiological findings in the patients with the recurrent vulvovaginal candidiasis (RVVC) with a focus on the establishment of fungal etiology and its in vitro antifungal susceptibility . DESIGN: Retrospective clinical and laboratory study . SETTING: Department of Obstetrics and Gynecology, Medical Faculty Hradec Kralove, Charles University, Prague, Department of Clinical Microbiology, Medical Faculty Hradec Kralove, Charles University, Prague, Department of Biological and Medical Sciences, Faculty of Pharmacy Hradec Kralove, Charles University, Prague . METHODS: An analysis of clinical and anamnestic data in outpatients of the Dept . of Obstetrics and Gynecology and the laboratory data from the microbiological examinations performed in the Dept . of Clinical Microbiology from 1995 to 2002 . RESULTS: Candida albicans accounted for 88.5% of the episodes of RVVC in the setting of 56 patients . Non-albicans Candida species were represented especially by C . glabrata (4.9%) and C . krusei (3.1%) . There were no considerable differences between the spectrum of RVVC and acute vulvovaginal candidiasis with the exception of Saccharomyces cerevisiae (0.7% in RVVC vs . 3.7% in acute VVC) . Mycological findings in 61 (20.5%) samples were accompanied by bacterial microbiota with the predominance of Streptococcus agalactiae (n = 15) and Gardnerella vaginalis (n = 9) . Decreased antifungal susceptibility determined by the disk test was observed in the strains of C . glabrata, C . krusei and S . cerevisiae, the other yeast isolates being susceptible to all ten antifungal drugs tested . CONCLUSION: The microbiological examination was decisive for the establishment of the diagnosis of RVVC in most cases . The most frequent etiological agents responsible for the attacks of RVVC as well as for acute vulvovaginal candidiasis was C . albicans, which was generally susceptible to antifungal drugs. Biophys J, 2004 May, 86(5), 3141 - 51 The role of cholesterol in the activity of pneumolysin, a bacterial protein toxin; Nollmann M et al.; The mechanism via which pneumolysin (PLY), a toxin and major virulence factor of the bacterium Streptococcus pneumoniae, binds to its putative receptor, cholesterol, is still poorly understood . We present results from a series of biophysical studies that shed light on the interaction of PLY with cholesterol in solution and in lipid bilayers . PLY lyses cells whose walls contain cholesterol . Using standard hemolytic assays we have demonstrated that the hemolytic activity of PLY is inhibited by cholesterol, partially by ergosterol but not by lanosterol and that the functional stoichiometry of the cholesterol-PLY complex is 1:1 . Tryptophan (Trp) fluorescence data recorded during PLY-cholesterol titration studies confirm this ratio, reveal a significant blue shift in the Trp fluorescence peak with increasing cholesterol concentrations indicative of increasing nonpolarity in the Trp environment, consistent with cholesterol binding by the tryptophans, and provide a measure of the affinity of cholesterol binding: K(d) = 400 +/- 100 nM . Finally, we have performed specular neutron reflectivity studies to observe the effect of PLY upon lipid bilayer structure. Virology, 2004 May 1, 322(2), 239 - 52 Genomic organization and molecular analysis of the inducible prophage EJ-1, a mosaic myovirus from an atypical pneumococcus; Romero P et al.; We report the complete genomic sequence of EJ-1, an inducible prophage isolated from an atypical Streptococcus pneumoniae strain that belongs to the Myoviridae morphology family . The phage and bacterial recombinational sites (attachment sites) have been also determined . The genome of the EJ-1 prophage (42935 bp) is organized in 73 open reading frames (ORFs) and in at least five major clusters . Bioinformatic and N-terminal amino acid sequence analyses enabled the assignment of possible functions to 52 ORFs . The predicted proteins coded for the EJ-1 genome revealed similarities in the lysogeny, DNA replication, regulation, packaging, and head morphogenesis protein clusters with those from several siphoviruses infecting lactic acid bacteria . However, the proteins encoded by genes orf53 to orf64, corresponding to putative tail proteins of the virion, were very similar to those of the defective Bacillus subtilis myovirus PBSX with the notable exception of the gene product of orf56 (the tape measure tail protein) that was similar to proteins from phages infecting Gram-negative bacteria . The first description of the genome of a myovirus infecting a low G + C content Gram-positive bacterium, a member of a group embracing important human pathogens and industrial relevant species, will contribute to expand our current knowledge on phage biology and evolution. Fish Shellfish Immunol, 2004 May, 16(5), 561 - 9 Dietary oligonucleotides from yeast RNA influence immune responses and resistance of hybrid striped bass (Morone chrysops x Morone saxatilis) to Streptococcus iniae infection; Li P et al.; Three feeding trials were conducted to evaluate potential immunomodulatory effects of nucleotides in the diet of hybrid striped bass . A basal diet was formulated from menhaden fish meal to contain 40% crude protein and 10% lipid . An oligonucleotide product (Ascogen P) from brewer's yeast was added to the basal formulation at the manufacturer's recommended rate of 0.5% to produce the experimental diet . Each diet was fed to four replicate groups of juvenile hybrid striped bass for seven or eight weeks in two separate trials . After Trials 1 and 2, a Streptococcus iniae bath challenge was executed to test the effects of diet on disease resistance . No significant difference in growth performance was observed between fish fed the basal and experimental diets . Body composition of whole fish, hematocrit and serum lysozyme levels were observed to be within normal ranges and not influenced by dietary nucleotides . Neutrophil oxidative radical production of fish fed the nucleotide-supplemented diet was significantly (P=0.011) higher than in fish fed the basal diet . Significantly (P<0.05) enhanced survival after exposure to S . iniae also was generally observed in fish fed the nucleotide-supplemented diet . In addition, fish fed the nucleotide-supplemented diet tended to have a higher antibody response based on microtitration agglutination; however, the difference was not statistically significant because of high variation between individual fish . Long-term (16 weeks) administration of oligonucleotides in Trial 3 failed to show enhancement of immune responses between treatments . It is concluded that dietary oligonucleotides positively influenced immune responses and resistance of juvenile hybrid striped bass to S . iniae infection. J Travel Med, 2004 Mar-Apr, 11(2), 87 - 91 Pneumonia among travelers returning from abroad; Ansart S et al.; BACKGROUND: Although respiratory tract infections represent a frequent cause of morbidity in travelers, and pneumonia a frequent cause of medical consultation among febrile travelers returning home, the etiologic spectrum of pneumonia in travelers has not been specifically studied . METHODS: We reviewed the medical charts of all travelers hospitalized during a 12-month period in our department with pneumonia after returning home . RESULTS: Seventeen patients (nine men, eight women, mean age 44 years, range 26 to 67 years) were included in this study . The etiology of pneumonia was established in 13 patients . Bacterial pneumonia was documented in 10 cases and was due to Streptococcus pneumoniae (n=2), Mycoplasma pneumoniae (n=2), Legionella pneumophila (n=1), Coxiella burnetti (n=1), Leptospira sp . (n=1) or Mycobacterium tuberculosis (n=3) . Other etiologies included histoplasmosis, invasive schistosomiasis and dengue fever (one case each) . CONCLUSION: These results show the wide range of causes of pneumonia among travelers returning from abroad. Emerg Infect Dis, 2004 Mar, 10(3), 514 - 7 Antibiotic selection pressure and resistance in Streptococcus pneumoniae and Streptococcus pyogenes; Albrich WC et al.; We correlated outpatient antibiotic use with prevalence of penicillin-nonsusceptible Streptococcus pneumoniae (PNSP), macrolide-resistant S . pneumoniae (MRSP), and macrolide-resistant S . pyogenes (MRGAS) in 20 countries . Total antibiotic use was correlated with PNSP (r = 0.75; p < 0.001), as was macrolide use with MRSP (r = 0.88; p < 0.001) and MRGAS (r = 0.71; p = 0.004) . Streptococcal resistance is directly associated with antibiotic selection pressure on a national level. Infect Dis Obstet Gynecol, 2003, 11(4), 199 - 202 Screening protocols for group B streptococcus: are transport media appropriate? Teese N, Henessey D, Pearce C, Kelly N, Garland S. OBJECTIVE: To evaluate group B streptococcus (GBS) detection in an in vitro setting, using a low and controlled inoculum from swabs directly inoculated into a selective medium, as compared to delayed inoculation following a period in a commercial Amies transport medium with charcoal (Venturi Transystem Copan, Italy) . STUDY DESIGN: Clinical isolates of GBS (n = 103), were inoculated into the Amies transport medium with charcoal in a concentration of 100 colony-forming units (cfu)/ml (10 cfu/swab) . Swabs were then transferred to an enrichment broth (NPC) at time intervals of 0, 2, 4, 6 and 24 hours . Broths were then incubated for 18-24 hours at 35 degrees C in air, before being transferred to New Granada Medium Modified (NGM) for GBS detection and incubated for a further 18-24 hours at 35 degrees C in air . If the characteristic orange pigmented colonies were observed after this period, the specimen was recorded as + (1-10 colonies) or + + (more than 10 colonies) . RESULTS: Overall 92.2% (95/103) of isolates were detected in all tubes and at all times . An additional two isolates were non-hemolytic, non-pigment forming GBS . Of note, 3.9% (4/103) were negative until 2 hours delayed inoculation and 1.9% (2/103) gave inconsistent results, likely due to the low inoculum used . CONCLUSION: Delayed inoculation into selective enrichment broth following a period in transport medium, even with a low inoculum, gave a similar and acceptable GBS detection rate to direct inoculation . Hence, Amies transport medium with charcoal is an appropriate transport medium to use, where it is not practical for clinical specimens to be directly inoculated into selective enrichment broth and as endorsed in the Centers for Diseases Control (CDC) Guidelines, 2002. N Z Med J . 2004 Apr 23;117(1192):U847. Skin infections of the limbs of Polynesian children; Finger F et al.; AIM: The aim of this study was to obtain information regarding the incidence of cellulitis or cutaneous abscess in children of Polynesian ethnicity (including New Zealand Maori), and to calculate the relative risk increase versus other ethnicities . METHODS: We reviewed all patients aged between 1 to 14 years who were admitted at our tertiary care institution during the year 2000 . Ninety-one children (of 10 different ethnicities) with skin infections were identified . RESULTS: The most common diagnosis was cutaneous abscess (46 of 91 cases, 50.5%), followed by cellulitis (45 of 91 cases, 49.5%) . The most common location of infection was the lower limb (79.1%) . The major pathogenic organisms were Staphylococcus aureus and Streptococcus pyogenes . All but one of the children had an uneventful recovery . The incidence of infection in the Polynesian children was 137.7 per 100,000, and the incidence in European children (and children of other ethnic groups) was 35.4 per 100,000 . In addition, we calculated a relative risk increase of 3.89 (95% confidence interval of 2.33 to 6.52, p <0.05), which underlines the increased risk that Polynesian children suffer from skin infection . CONCLUSION: This is the first study showing (in detail) how Polynesian children are affected by a high incidence and increased relative risk of skin infections in their limbs (arms and legs) . However, further research (to identify whether genetic disposition or social and environmental circumstances are involved) is required. Indian J Pediatr, 2004 Apr, 71(4), 319 - 24 Efficacy and tolerability assessment of cefprozil in children with acute otitis media; Gupta N et al.; Young children contract as many as six to eight upper respiratory tract viral infections per year, and these infections frequently lead to secondary bacterial infections such as acute otitis media and sinusitis . Cefprozil is an orally active third generation cephalosporin which has demonstrated activity against the gram-positive organisms Streptococcus pyogenes, pneumoniae and agalactiae and against methicilin-susceptible Staphylococcus aureus . Cefprozil is also active against various gram-ves and certain anaerobic organisms, and is stable to hydrolysis by a number of b-lactamases . Present study is an effort to study the efficacy and safety of cefprozil in children with acute otitis media . Three hundred and thirty four children aged 6 months through 12 years with clinical symptoms and tympanic membrane signs of AOM received cefprozil 30 mg/kg/day in two divided doses per day for 10 days . Clinically, 96.6% patients were cured, 2.4% improved and there was failure of therapy in 1% of the patients . There was no need for any rescue medication and any change in antibiotic in any patient . A satisfactory bacteriological outcome was (i.e . cure, presumed cure, and cure plus reinfection with a different pathogen) was achieved in 95% of patients . In conclusion, cefprozil is a well tolerated and effective drug for acute otitis media in children . Moreover, its expanded spectrum of activity, ability to achieve adequate concentrations in tissues, suitability for twice-daily dosing, and proven tolerability suggest that it is a better alternative to agents conventionally used in acute otitis media. Oral Microbiol Immunol, 2004 Jun, 19(3), 210 - 3 Deletion in sortase gene of Streptococcus mutans Ingbritt; Igarashi T; Our previous studies on Streptococcus mutans have demonstrated that surface proteins containing a C-terminal sorting signal, such as surface protein antigen (PAc), glucan-binding protein C (GbpC) and dextranase (Dex), are anchored to the cell wall by a sortase (SrtA) . In this study we found that, unlike other strains of S . mutans, strain Ingbritt did not exhibit cell wall-anchoring of PAc, GbpC and Dex . It is speculated that the SrtA of strain Ingbritt did not function in the cell wall-anchoring process of these surface proteins . Sequence analysis revealed a deletion of an 11-bp nucleotide sequence in the srtA gene of strain Ingbritt, resulting in the generation of a new termination codon, resulting in production of an incomplete SrtA enzyme protein . As a result, strain Ingbritt showed a localization change of PAc, GbpC and Dex in the cell, implying that strain Ingbritt loses the biological functions mediated by the cell surface-associated proteins of S . mutans . These results suggest that strain Ingbritt could be less cariogenic than other strains of S . mutans . Copyright Blackwell Munksgaard, 2004. Cochrane Database Syst Rev . 2004;(2):CD000023. Antibiotics for sore throat; Del Mar CB et al.; BACKGROUND: Sore throat is a very common reason for people to seek medical care . It is a disease that remits spontaneously, that is, 'cure' is not dependent on treatment . Nonetheless primary care doctors commonly prescribe antibiotics for sore throat and other upper respiratory tract infections . OBJECTIVES: To assess the benefits of antibiotics in the management of sore throat . SEARCH STRATEGY: Systematic search of the literature from 1945 to 2003, using electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, issue 2, 2003); MEDLINE (January 1966 to May 2003); EMBASE (January 1990 to March 2003), and the reference sections of the articles identified . We applied no language restrictions . We used abstracts of identified articles to identify trials . SELECTION CRITERIA: Trials of antibiotic against control with either measures of the typical symptoms (throat soreness, headache or fever), or suppurative complications (meaning: forming pus) and non-suppurative complications of sore throat . DATA COLLECTION AND ANALYSIS: Two reviewers independently screened potential studies for inclusion and resolved differences in opinion by discussion . The reviewers then independently extracted the data from the selected studies . We contacted the authors of three studies to acquire additional information not available in published articles.Potential studies were screened independently by two reviewers for inclusion, with differences in opinion resolved by discussion . Data was then independently extracted from studies selected by inclusion by two reviewers . Authors of three studies were contacted to acquire additional information not available in published articles . MAIN RESULTS: We included twenty-six studies, covering 12,669 cases of sore throat in the review.1 . Non-suppurative complications There was a trend for protection against acute glomerulonephritis by antibiotics, but insufficient cases were recorded to be sure of this effect . Several studies found that antibiotics reduced acute rheumatic fever, to less than one third (odds ratio (OR) = 0.30; 95% confidence interval (CI) = 0.20 to 0.45) . 2 . Suppurative complications Antibiotics reduced the incidence of acute otitis media to about one quarter of that in the placebo group (OR = 0.22; 95% CI 0.11 to 0.43) and reduced the incidence of acute si