Streptococcal

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 sinusitis to about one half of that in the placebo group (OR = 0.46; 95% CI 0.10 to 2.05) . The incidence of quinsy was also reduced in relation to placebo group (OR = 0.16; 95% CI 0.07 to 0.35) . 3 . Symptoms Symptoms of headache, throat soreness and fever were reduced by antibiotics to about one half . The greatest time for this to be evident was at about three and a half days (when the symptoms of about 50% of untreated patients had settled) . About 90% of treated and untreated patients were free of symptoms by one week . The overall number needed to treat to prevent one sore throat at day three was about 5.0 (95% CI 4.5 to 5.8); and at one week was 14.2 (95% CI 11.5 to 20.6) . 4 . Subgroup analyses of symptom reduction Subgroup analysis by age; blind versus unblinded; or use of antipyretics yielded no significant differences . The results of swabs of the throat for Streptococcus influenced the effect of antibiotics . If the swab was positive, antibiotics were more effective (the OR reduced to 0.16, 95% CI 0.09 to 0.26) than if it was negative (OR 0.65; 95% CI 0.38 to 1.12) . REVIEWERS' CONCLUSIONS: Antibiotics confer relative benefits in the treatment of sore throat . However, the absolute benefits are modest . Protecting sore throat sufferers against suppurative and non-suppurative complications in modern Western society can be achieved only by treating with antibiotics many who will derive no benefit . In emerging economies where rates of for example acute rheumatic fever are high, the number needed to treat may be much lower . Antibiotics shorten the duration of symptoms by a mean of one day about half way through the illness (the time of maximal effect), and by about sixteen hours overall.

Antimicrob Agents Chemother, 2004 May, 48(5), 1882 - 4
Activities of telithromycin against 13,874 Streptococcus pneumoniae isolates collected between 1999 and 2003; Farrell DJ et al.; Telithromycin MICs for 13,874 Streptococcus pneumoniae isolates collected in the first 3 years of the global PROTEKT study (1999 to 2003) were studied . There was no change in the distribution of telithromycin MICs over this period, even in countries where telithromycin is in use . The telithromycin MICs for 10 isolates (0.07%) were >/=4 micro g/ml, and these 10 isolates contained erm(B); there was no evidence of reproducible clonal spread between centers.

Antimicrob Agents Chemother, 2004 May, 48(5), 1624 - 9
Feasibility of radioimmunotherapy of experimental pneumococcal infection; Dadachova E et al.; Streptococcus pneumoniae is an important cause of community-acquired pneumonia, meningitis, and bacteremia . The problem of pneumococcal disease is exacerbated by increasing drug resistance . Furthermore, patients with impaired immunity are at high risk for invasive pneumococcal infections . Thus, there is an urgent need for new approaches to antimicrobial therapy . Antibody therapies take advantage of the specificity and high affinity of the antigen-antibody interaction to deliver antibacterial compounds to a site of infection in the form of naked or conjugated antibodies . We have recently established that radioimmunotherapy (RIT) can be used to treat experimental fungal infections in mice . In the present study, we investigated the feasibility of applying a RIT approach to the treatment of S . pneumoniae infection by evaluating the susceptibility of S . pneumoniae to radiolabeled antibody in vitro and in an animal infection model . For the specific antibody carrier, we used human monoclonal antibody D11, which binds to pneumococcal capsular polysaccharide 8 . We have selected the alpha particle emitter (213)Bi as the radionuclide for conjugation to the antibody . Incubation of serotype 8 S . pneumoniae with (213)Bi-D11 resulted in dose-dependent killing of bacteria . RIT of S . pneumoniae infection in C57BL/6 mice showed that 60% more mice survived in the (213)Bi-D11-treated group (80 micro Ci) than in the untreated group (P < 0.01) . The treatment did not cause hematological toxicity, as demonstrated by platelet counts . This feasibility study establishes that RIT can be applied to the treatment of bacterial infections.

Antimicrob Agents Chemother, 2004 May, 48(5), 1526 - 33
Antibacterial activities of rhodamine B-conjugated gelsolin-derived peptides compared to those of the antimicrobial peptides cathelicidin LL37, magainin II, and melittin; Bucki R et al.; The growing number of antibiotic-resistant bacteria necessitates the search for new antimicrobial agents and the principles by which they work . We report that cell membrane-permeant rhodamine B (RhB)-conjugated peptides based on the phosphatidylinositol-4,5-bisphosphate binding site of gelsolin can kill the gram-negative organisms Escherichia coli and Pseudomonas aeruginosa and the gram-positive organism Streptococcus pneumoniae . RhB linkage to the QRLFQVKGRR sequence in gelsolin was essential for the antibacterial function, since the unconjugated peptide had no effect on the bacteria tested . Because RhB-QRLFQVKGRR (also termed PBP10), its scrambled sequence (RhB-FRVKLKQGQR), and PBP10 synthesized from D-isomer amino acids show similar antibacterial properties, the physical and chemical properties of these derivatives appear to be more important than specific peptide folding for their antibacterial functions . The similar activities of PBP10 and all-D-amino-acid PBP10 also indicate that a specific interaction between RhB derivatives and bacterial proteins is unlikely to be involved in the bacterial killing function of PBP10 . By using a phospholipid monolayer system, we found a positive correlation between the antibacterial function of PBP10, as well as some naturally occurring antibacterial peptides, and the intrinsic surface pressure activity at the hydrophobic-hydrophilic interface . Surprisingly, we observed little or no dependence of the insertion of these peptides into lipid monolayers on the phospholipid composition . These studies show that an effective antimicrobial agent can be produced from a peptide sequence with specificity to a phospholipid not found in bacteria, and comparisons with other antimicrobial agents suggest that the surface activities of these peptides are more important than specific binding to bacterial proteins or lipids for their antimicrobial functions.

Antimicrob Agents Chemother, 2004 May, 48(5), 1488 - 94
Antibiotic susceptibility in relation to penicillin-binding protein genes and serotype distribution of Streptococcus pneumoniae strains responsible for meningitis in Japan, 1999 to 2002; Ubukata K et al.; The antibiotic susceptibilities, genotypes of penicillin (PEN)-binding protein genes (pbp), and serotype distributions of Streptococcus pneumoniae isolates from meningitis patients were investigated by a nationwide surveillance group in Japan between 1999 and 2002 . We analyzed 146 isolates from children (</=17 years old) and 73 from adults (>/=18 years old) . Isolates with or without abnormal pbp1a, pbp2x, or pbp2b genes identified by PCR were classified into six genotype patterns and 90% MIC (MIC(90)) values for PEN: (i) strains with three normal genes (17.2% of isolates; MIC(90), 0.031 micro g/ml); (ii) strains with abnormal pbp2x (22.1%, 0.063 micro g/ml); (iii) strains with abnormal pbp2b (1.0%, 0.125 micro g/ml); (iv) strains with abnormal pbp2x and pbp2b (7.4%, 0.25 micro g/ml); (v) strains with abnormal pbp1a and pbp2x (12.7%, 0.25 micro g/ml); and (vi) strains with three abnormal PBP genes (39.7%, 4 micro g/ml), which are termed genotypic PEN-resistant S . pneumoniae (gPRSP) . Panipenem, a carbapenem, showed an excellent MIC(90) (0.125 micro g/ml) against gPRSP, followed by meropenem and vancomycin (0.5 micro g/ml), cefotaxime and ceftriaxone (1 micro g/ml), and ampicillin (4 micro g/ml) . Strains of gPRSP were significantly more prevalent in children (45.2%) than in adults (27.4%) . The most frequent serotypes were 6B, 19F, 23F, 6A, and 14 in children and 23F, 22, 3, 10, 6B, and 19F in adults . Serotypes 6B, 6A, 19F, 23F, and 14 predominated among gPRSP . In children, 7- and 11-valent pneumococcal conjugate vaccines would cover 76.2 and 81.3% of isolates, respectively, although coverage would be lower in adults (43.9 and 56.0%, respectively) . These findings suggest the need for early introduction of pneumococcal conjugate vaccines and continuous bacteriological surveillance for meningitis.

An Pediatr (Barc), 2004 May, 60(5), 459 - 67
{What is the importance of bacterial eradication in the treatment of respiratory tract infections?}; Gonzalo de Liria CR; During the last few years, increasing antibiotic resistance amongst the major respiratory pathogens in the community has compromised the choice of empirical therapy for some respiratory tract infections . Of special interest has been the progressive increase in the resistance rates of Streptococcus pneumoniae to macrolides and penicillin, and of S . pyogenes to macrolides.Several studies have confirmed the association between community use of certain antibiotics and the development of resistance in S . pneumoniae and S . pyogenes . Nevertheless, not all the antibiotics have the same ability to select resistance and not all microorganisms are affected in the same way.The aim of antimicrobial therapy in respiratory tract infections is bacterial eradication . Pharmacokinetic and pharmacodynamics can be used to predict bacteriological eradication with antimicrobial therapy.

Kansenshogaku Zasshi, 2004 Feb, 78(2), 108 - 13
{Comparison of clinical presentation of mixed pneumonia with Chlamydia pneumoniae and Streptococcus pneumoniae and S . pneumoniae pneumonia}; Fukano H et al.; Chlamydia pneumoniae is a significant cause of both lower and upper acute respiratory illnesses, including community-acquired pneumonia . Furthermore, C . pneumoniae has been reported to frequently cause pneumonia in association with other respiratory pathogens, mainly Streptococcus pneumoniae . In this study, we investigated the clinical presentation of mixed pneumonia with Chlamydia pneumoniae and S . pneumoniae and compared it with S . pneumoniae pneumonia . A total of 13 cases of mixed pneumonia and 58 cases of S . pneumoniae pneumonia identified at Kawasaki Medical School and related hospitals between April 1996 and March 2001 were analyzed . The diagnosis of C . pneumoniae infection was based on isolation and serologic testing of antibodies by the microimmunofluorescence test . The clinical presentation of mixed pneumonia and S . pneumoniae pneumonia was almost identical and no statistical differences were observed between the two groups . This is the same as what was observed before except eleven out of the 13 of the mixed pneumonia patients responded to treatment with only beta-lactam antibiotics . Our results indicated that C . pneumoniae may not be the primary cause of community-acquired pneumonia but it might descript the normal clearance mechanisms, enabling other pathogens to invade.

Kansenshogaku Zasshi, 2004 Jan, 78(1), 10 - 7
{Epidemiological study on Streptococcus pyogenes strains isolated from the patients with streptococcal toxic shock syndrome (STSS) in Japan in 1992-2001}; Okuno R et al.; To investigate clinical and microbiological features of streptococcal toxic shock syndrome (STSS), clinical, epidemiological, and bacteriological data obtained from 250 patients between 1992 and 2001 were analyzed . Among these 250 cases, 16 cases were excluded from the study because the causative microorganism were not Streptococcus pyogenes . 234 strains of S . pyogenes obtained from the aforementioned 234 cases were tested for T-type by a serological method, and for streptococcal pyrogenic exotoxin (SPE) by in vitro productivity of the toxin as well as molecular genetic methods . The number of patients was 141 (56.4%) for males, and 107 (42.8%) for females . The highest frequency of STSS was observed in those patients in their sixties in both sexes . The overall mortality rate was 43.2% . The mortality rate for male was 36.9%, and 52.3% for female . Bacteriological studies revealed that most common T types were T1 and T3 . These strains consisted 54.3% of the strains collected . Among strains of T1 type, 98.8% possessed genes of spe A, and 46.1% were shown to produce SPE A in vitro . Among strains of T3 type, 82.9% possessed spe A gene, and all of these strains were shown to produce the toxin in vitro . It is concluded that certain strains of S . pyogenes, such as those with T1, or T3 type, and those with spe A gene or in vitro production of SPE A, are the most frequent cause of STSS . Although infections caused by such bacteria are quite common, STSS rarely occurs in most such patients . Additional factors, such as host factors, may play a crucial role in the pathogenesis of STSS.

EMBO J, 2004 May 19, 23(10), 2166 - 74 Epub 2004 Apr 22.
Interactions with fibronectin attenuate the virulence of Streptococcus pyogenes; Nyberg P et al.; Fibronectin-binding surface proteins are found in many bacterial species . Most strains of Streptococcus pyogenes, a major human pathogen, express the fibronectin-binding protein F1, which promotes bacterial adherence to and entry into human cells . In this study, the role of fibronectin in S . pyogenes virulence was investigated by introducing the protein F1 gene in an S . pyogenes strain lacking this gene . Furthermore, transgenic mice lacking plasma fibronectin were used to examine the relative contribution of plasma and cellular fibronectin to S . pyogenes virulence . Unexpectedly, protein F1-expressing bacteria were less virulent to normal mice, and virulence was partly restored when these bacteria were used to infect mice lacking plasma fibronectin . Dissemination to the spleen of infected mice was less efficient for fibronectin-binding bacteria . These bacteria also disseminated more efficiently in mice lacking plasma fibronectin, demonstrating that plasma fibronectin bound to the bacterial surface downregulates S . pyogenes virulence by limiting bacterial spread . From an evolutionary point of view, these results suggest that reducing virulence by binding fibronectin adds selective advantages to the bacterium.

Acta Crystallogr D Biol Crystallogr, 2004 May, 60(Pt 5), 950 - 1 Epub 2004 Apr 21.
Crystallization and preliminary crystallographic studies of the D59A mutant of MicA, a YycF response-regulator homologue from Streptococcus pneumoniae; Riboldi-Tunnicliffe A et al.; RR02 (MicA) is an essential bacterial protein that belongs to the YycF family of response regulators and consists of two domains: an N-terminal receiver domain and a C-terminal effector domain . Streptococcus pneumoniae RR02 (MicA; residues 2-234) has been crystallized using the sitting-drop vapour-diffusion technique . The crystals belong to space group P2(1), with unit-cell parameters a = 46.46, b = 32.61, c = 63.35 A, beta = 90.01 degrees . X-ray diffraction data have been collected to 1.93 A resolution.

Acta Crystallogr D Biol Crystallogr, 2004 May, 60(Pt 5), 926 - 8 Epub 2004 Apr 21.
Expression, purification and X-ray characterization of residues 18-230 from the pneumococcal histidine triad protein A (PhtA) from Streptococcus pneumoniae; Riboldi-Tunnicliffe A et al.; A fragment of the Streptococcus pneumoniae PhtA gene product (residues 18-230) was cloned and overexpressed in Escherichia coli . The purified protein was crystallized using the sitting-drop vapour-diffusion technique . Crystals belong to the monoclinic space group C2, with unit-cell parameters a = 62.19, b = 35.9, c = 72.54 A, beta = 90.01 degrees . The crystals diffract X-rays to beyond 1.2 A resolution.

Pediatr Res, 2004 Jun, 55(6), 972 - 8 Epub 2004 Apr 21.
Enhanced adherence of Streptococcus pneumoniae to human epithelial cells infected with respiratory syncytial virus; Hament JM et al.; In the present study, we analyzed the effect of a preceding respiratory syncytial virus (RSV) infection of human respiratory epithelial cells on the adherence of Streptococcus pneumoniae tested by means of a cytometric fluorescence assay . Adherence of clinically relevant pneumococcal serotypes 3, 9, 14, 18, 19, and 23 was studied using uninfected and RSV-infected monolayers . To this end, monolayers of both human nasopharyngeal cells (HEp-2) and pneumocyte type II cells (A549) were infected with RSV serotype A . Adherence to uninfected epithelial cells varied between pneumococcal serotypes . After RSV infection of the monolayers, all serotypes showed a strongly (2- to 10- fold) and significantly increased adherence when compared with adherence to uninfected monolayers . Enhanced adherence was observed with both cell lines . By fluorescence and scanning electron microscopy, we observed redistribution of pneumococcal adherence over the epithelial surface due to RSV infection, with dense bacterial accumulations near to epithelial syncytia.

Infect Immun, 2004 May, 72(5), 3084 - 7
Porcine choroid plexus epithelial cells induce Streptococcus suis bacteriostasis in vitro; Adam RA et al.; The involvement of the choroid plexus in host defense during bacterial meningitis is unclear . Aiming to elucidate possible antibacterial mechanisms, we stimulated primary porcine choroid plexus epithelial cells (pCPEC) with proinflammatory cytokines and challenged them with various Streptococcus suis strains . In the supernatant of gamma interferon (IFN-gamma)-stimulated pCPEC, streptococcal growth was markedly suppressed . Costimulation with tumor necrosis factor alpha enhanced this bacteriostatic effect, while supplementation of L-tryptophan completely eliminated it . We also demonstrate that an activation of indoleamine 2,3-dioxygenase in the pCPEC seems to be responsible for the IFN-gamma-induced bacteriostasis . This supports the hypothesis of an active role of the choroid plexus in host defense against bacterial meningitis.

Infect Immun, 2004 May, 72(5), 3077 - 80
Pneumococcal surface protein C contributes to sepsis caused by Streptococcus pneumoniae in mice; Iannelli F et al.; The role of pneumococcal surface protein C (PspC; also called SpsA, CbpA, and Hic) in sepsis by Streptococcus pneumoniae was investigated in a murine infection model . The pspC gene was deleted in strains D39 (type 2) and A66 (type 3), and the mutants were tested by being injected intravenously into mice . The animals infected with the mutant strains showed a significant increase in survival, with the 50% lethal dose up to 250-fold higher than that for the wild type . Our findings indicate that PspC affords a decisive contribution to sepsis development.

Infect Immun, 2004 May, 72(5), 2964 - 75
LuxS is required for persistent pneumococcal carriage and expression of virulence and biosynthesis genes; Joyce EA et al.; Streptococcus pneumoniae causes several diseases, including otitis media, pneumonia, and meningitis . Although little is known about the regulation of or how individual pneumococcal factors contribute to these disease states, there is evidence suggesting that some factors are regulated by a cell-density-dependent mechanism (quorum sensing) . Quorum sensing allows bacteria to couple transcription with changes in cell density; bacteria achieve this by sensing and responding to small diffusible signaling molecules . We investigated how the LuxS signaling system impacts the biology of S . pneumoniae . An analysis of the transcriptional profiles of a serotype 2 strain and an isogenic luxS deletion strain utilizing an S . pneumoniae-specific microarray indicated that LuxS regulates gene expression involved in discrete cellular processes, including pneumolysin expression . Contrary to the paradigm for quorum sensing, we observed pronounced effects on transcription in early log phase, where gene expression was repressed in the mutant . Assessing the mutant for its ability to infect and cause disease in animals revealed a profound defect in ability to persist in the nasopharyngeal tissues . Our analysis of an S . pneumoniae transcriptome revealed a function for LuxS in gene regulation that is not dependent upon high cell density and is likely involved in the maintenance of pneumococcal load in susceptible hosts.

Infect Immun, 2004 May, 72(5), 2689 - 97
CD4-T-lymphocyte interactions with pneumolysin and pneumococci suggest a crucial protective role in the host response to pneumococcal infection; Kadioglu A et al.; Previously, we had shown that T cells accumulated in peribronchiolar and perivascular areas of lungs soon after intranasal infection with Streptococcus pneumoniae . We have now presented new evidence, using major histocompatibility class II-deficient mice, that CD4 cells are important for early protective immunity . In addition, we have also shown that a population of human CD4 cells migrates towards pneumococci and that in vivo-passaged pneumococci are substantially more potent at inducing migration than in vitro-grown bacteria . This migratory process is unique to a specific population of CD4 cells, is highly reproducible, and is independent of prior CD4 cell activation, and yet the migratory process results in a significant proportion of CD4 cells becoming activated . The production of pneumolysin is a key facet in the induction of migration of CD4 cells by in vivo bacteria, as pneumolysin-deficient bacteria do not induce migration, but the data also show that pneumolysin alone is not sufficient to explain the enhanced migration . Increased CD25 expression occurs during migration, and a higher percentage of cells in the migrated population express gamma interferon or interleukin 4 (IL-4) than in the population that did not migrate . There is evidence that the activation of IL-4 expression occurs during migration.

Infect Immun, 2004 May, 72(5), 2659 - 70
Prevention of pneumococcal disease in mice immunized with conserved surface-accessible proteins; Hamel J et al.; The development of a vaccine against Streptococcus pneumoniae has been complicated by the existence of at least 90 antigenically distinct capsular serotypes . Common protein-based vaccines could represent the best strategy to prevent pneumococcal infections, regardless of serotype . In the present study, the immunoscreening of an S . pneumoniae genomic library allowed the identification of a novel immune protein target, BVH-3 . We demonstrate that immunization of mice with BVH-3 elicits protective immunity against experimental sepsis and pneumonia . Sequence analysis revealed that the bvh-3 gene is highly conserved within the species . Since the BVH-3 protein shows homology at its amino-terminal end with other pneumococcal proteins, it was of interest to determine if protection was due to the homologous or to the protein-specific regions . Immunoprotection studies using recombinant BVH-3 and BVH-3-related protein fragments as antigens allowed the localization of surface-exposed and protective epitopes at the protein-specific carboxyl termini, thus establishing that BVH-3 is distinct from other previously reported protective protein antigens . Immunization with a chimeric protein comprising the carboxyl-terminal regions of BVH-3 and of a BVH-3-related protein improved the protection by targeting two surface pneumococcal components . Thus, BVH-3 and the chimeric protein hold strong promise as vaccine components to control pneumococcal disease.

Klin Mikrobiol Infekc Lek, 2004 Feb, 10(1), 16 - 21
{Telithromycin}; Benes J; For the time being telithromycin is the only representative of a new group of antibiotics - ketolides - available for clinical use . Its chemical structure is derived from erythromycin, but it is better resorbed from the digestive tract and is efficacious against most macrolide-resistant strains of Streptococcus pneumoniae and Streptococcus pyogenes . Telithromycin is registered for the treatment of respiratory infections: sinusitis, acute exacerbation of chronic bronchitis, community-acquired pneumonia and streptococcal tonsillopharyngitis . The drug is well tolerated . It is less likely to induce MLS(B) resistance than macrolides with a 14- or 15-member ring.

J Allergy Clin Immunol, 2004 Apr, 113(4), 620 - 6
Phagocyte immunodeficiencies and their infections; Rosenzweig SD et al.; Primary immunodeficiencies (PIDs) primarily affecting the phagocytes (neutrophils and macrophages) typically predispose patients to infections . However, one of the most clinically important features of these disorders is their relatively narrow spectrum of disease-specific infections . Invasive aspergillosis in the absence of immune suppression is essentially seen only in chronic granulomatous disease; disseminated nontuberculous mycobacterial infection in the absence of immune suppression is seen predominantly in patients with defects of the IFN-gamma/IL-12 axis . In contrast, infections that are relatively common in some of the PIDs affecting the lymphoid system (Pneumocystis jiroveci and Streptococcus pneumoniae) are extremely uncommon in PIDs affecting phagocytes . Therefore careful attention to the microbiology laboratory early in the course of evaluation of a patient with recurrent infections and suspected of having a PID will help steer the workup in the appropriate direction . Over the last few years, there have been major advances in the molecular and cellular understandings of PIDs affecting phagocytes . As the field of PIDs becomes broader and more clinical and molecular definition becomes available, it is increasingly important to be able to identify likely pathways for investigation early in the evaluation . Here we have updated some of the more rapidly evolving aspects of PIDs affecting phagocytes, with a special emphasis on the associated microbiology.

Restor Neurol Neurosci, 2004, 22(1), 33 - 41
Macrophage stimulation using a group B-streptococcus exotoxin (CM101) leads to axonal regrowth in the injured optic nerve; Ohlsson M et al.; PURPOSE: A group B-streptococcus exotoxin (CM101) was administered following optic nerve injury in adult rats in order to analyze putative effects on macrophages, glial scar formation and regrowth of axons in the lesioned optic nerve . METHODS: After a standardized intraorbital optic nerve crush, animals were randomized to treatment with CM101 (30 microm/kg body weight, iv, repeated every other day) or vehicle alone . Morphology (semithin sections) and immunohistochemistry directed towards macrophages (ED1), neurofilament (NF), astrocytes (GFAP) and regenerative sprouts (GAP43) were employed at different time-points up to 28 dpi . RESULTS: A significant increase of ED1-positive macrophages (p < 0.05) was observed at 7, 14 and 28 dpi in treated animals compared to untreated, indicative of macrophage stimulation . Less degenerative structures were found in sections distal to the injury in treated animals, seemingly due to a pro-phagocytic effect . Reactive gliosis was significantly (p < 0.05) less pronounced in CM101-treated animals . The presence of GAP43-positive sprouts and neurofilament-positive neurites distal to the lesion in treated animals indicate regrowth of axons crossing the glial scar . CONCLUSION: Treatment with group B-streptococcus exotoxin leads to macrophage stimulation, increased phagocytosis of inhibitory debris, and a less dense reactive gliosis, which in turn allows for regrowth of axons through the glial scar.

J Mol Diagn, 2004 May, 6(2), 145 - 8
A novel Streptococcus organism identified in a case of fulminant endocarditis using 16S rDNA sequencing; Jobbagy Z et al.; We report the identification of a virulent Streptococcus organism associated with fulminant endocarditis, using 16S rRNA gene amplification, sequencing and assembly from formalin-fixed, paraffin-embedded archival heart valve tissue, years after the autopsy of a patient.

Clin Infect Dis, 2004 Apr 15, 38(8), 1095 - 101 Epub 2004 Mar 30.
Two regimens of azithromycin prophylaxis against community-acquired respiratory and skin/soft-tissue infections among military trainees; Guchev IA et al.; Epidemics of community-acquired pneumonia (CAP) are a frequent cause of morbidity among Russian military trainees . We evaluated azithromycin prophylaxis against CAP . In 2001-2002, incoming military trainees were randomized to 1 of 3 trial arms by training group: azithromycin, 500 mg per week for 8 weeks (R1); azithromycin, 1500 mg once at enrollment (R2); or no therapy (R3) . During the 22 weeks of training, CAP was diagnosed in 20.2% of 678 subjects in the R3 group, 8.6% of 508 subjects in the R1 group, and 10.3% of 507 subjects in the R2 group . Throat carriage cultures revealed that the proportion of Streptococcus pneumoniae isolates with resistance to macrolides correspondingly increased during the study, from 0% (all) to 40% (R1) and 22.6% (R2) by week 20 . Azithromycin prophylaxis is effective against CAP in a healthy population of young men at transient high risk of disease; however, azithromycin use must be tempered with the possible concomitant risk of selection for resistant endemic pathogens.

Clin Pediatr (Phila), 2004 Apr, 43(3), 261 - 7
Acute mastoiditis in children: epidemiologic, clinical, microbiologic, and therapeutic aspects over past years; Nussinovitch M et al.; Recent studies have indicated possible changes in the incidence of acute mastoiditis . A retrospective review of children discharged with a diagnosis of acute mastoiditis was undertaken to describe the epidemiology, clinical presentation, microbiology, and treatment of acute mastoiditis over past years . Demographic historic, clinical, and laboratory data were collected . Eighty-six children (88 episodes of acute mastoiditis) were identified (1 month-16 years) (median 3.3 years) . Almost half had a history of middle ear disease; 8% recurrent episodes and 68.2% received antibiotics preadmission, 91.2% for acute otitis media . Bacterial etiology was established in 43 patients (68.2% isolation rate) . Pseudomonas aeruginosa and Streptococcus pneumoniae were the most frequently isolated agents . This review showed a significant increase (150%) in the number of patients with acute mastoiditis.

Drugs Today (Barc), 1998 Jan, 34(1), 31 - 5
Penicillin-resistant pneumococci; Cunha BA; Penicillin-resistant pneumococci are of concern in respiratory tract infections . Currently, nearly all of the "penicillin resistance" to Streptococcus pneumoniae is relative resistance which indicates decreased antibiotic activity in terms of the MIC, but these isolates are still susceptible to sensitive antibiotics given in the usual/high doses . The emergence of highly resistant Streptococcus pneumoniae may be minimized by preferentially using antibiotics known to have a high degree of antipneumococcal activity with a low resistance potential, e.g., doxycycline, cefprozil, levofloxacin, cefepime or meropenem . While vancomycin is useful to treat highly resistant strains, its use should be decreased to minimize the emergence of VRE and strains of Staphylococcus aureus with intermediate vancomycin sensitivity . (c) 1998 Prous Science . All rights reserved.

Int J Cardiol, 2004 Apr, 94(2-3), 321 - 2
Austrian syndrome in a child-aortic valve endocarditis following pneumococcal meningitis; Rammeloo L et al.; A 7-year-old girl with a previously healthy heart underwent a Ross procedure after pneumococcal sepsis, meningitis and aortic valve endocarditis with extensive para-valvular involvement . While pneumococcal infections including respiratory tract infections, bacteraemia and meningitis are common in childhood, endocarditis caused by Streptococcus pneumoniae occurs rarely . Pneumococcal meningitis and aortic valve endocarditis is a known combination, described as Austrian syndrome . We suggest that children with pneumococcal meningitis should be screened with echocardiography for an aortic valve endocarditis . In case of aortic valve endocarditis and persistent infection, surgery should be considered early.

J Emerg Med, 2004 May, 26(4), 421 - 3
Blistering distal dactylitis: a case series in children under nine months of age; Lyon M et al.; Blistering distal dactylitis (BDD) is a distinct clinical entity that is infrequently reported in the literature . Characteristically, blistering distal dactylitis is described as a localized infection involving the volar fat pad of the distal phalanx of the digits, and it usually presents as a fluid-filled blister . The usual causative organism is group A beta-hemolytic Streptococcus, but less commonly, Staphyloccous aureus and Staphyloccoccus epidermis are present . The normal age range is reported to be 2 to 16 years old, but there are case reports of this infection in adults . Only one case has been reported in the literature in a child younger than 24 months of age . In this report we describe three cases in children younger than 9 months old . These three cases indicate that BDD can and does occur in children younger than 2 years of age.

Crit Care Med, 2004 Mar, 32(3), 625 - 31
Prospective observational study of bacteremic pneumococcal pneumonia: Effect of discordant therapy on mortality; Lujan M et al.; STUDY OBJECTIVE: To evaluate the effect of discordant empirical therapy on outcome in bacteremic pneumococcal community-acquired pneumonia . DESIGN: Prospective observational study . SETTING: A 600-bed teaching hospital with a reference area of 400,000 inhabitants . PATIENTS: All patients aged > or =18 yrs with a diagnosis of community-acquired pneumonia whose blood cultures, obtained within the first 48 hrs of hospitalization, demonstrated growth of Streptococcus pneumoniae were included in the study . METHODS: Discordant therapy was defined as failure to administer an antibiotic with in vitro activity against the isolated strain within 24 hrs of hospital admission . The 2002 breakpoints recommended for respiratory infections by the National Committee for Clinical Laboratory Standards were used to classify therapy . RESULTS: A total of 100 patients with bacteremic pneumococcal pneumonia were identified . Penicillin- and macrolide-resistant strains were identified in 29 and 18 cases, respectively . Only two strains had minimum inhibitory concentrations of >2 microg/mL for cephalosporins . Discordant therapy was documented in ten patients, five of whom died . Mortality in patients receiving concordant therapy was 14% (13 of 90) . Nursing home residence (odds ratio {OR} = 14.8) and immunocompromise (OR = 11.5) were independently (p <.05) associated with discordant therapy . Risk of discordant therapy was significantly higher (p <.05) when empirical therapy did not include cefotaxime or ceftriaxone (OR = 10.4) . Discordant therapy (OR = 27.3), multilobar involvement (OR = 14.2), underlying chronic obstructive pulmonary disease (OR = 9.1), and hospitalization during the previous 12 wks (OR = 7.9) were independently associated (p <.05) with death . The excess mortality for initial discordant therapy was estimated to be 35.6% (95% confidence interval, 3.73-67.4) . CONCLUSIONS: Survival in patients with bacteremic community-acquired pneumococcal pneumonia can be improved by avoiding suboptimal therapy . Using the 2002 breakpoints, it is very unlikely that discordant therapy would be given with ceftriaxone or cefotaxime . Clinical outcome is worse in those patients receiving antimicrobial therapy that in vitro testing suggests would be ineffective.

J Bacteriol, 2004 May, 186(9), 2872 - 9
Crystal structure of the response regulator 02 receiver domain, the essential YycF two-component system of Streptococcus pneumoniae in both complexed and native states; Bent CJ et al.; A variety of bacterial cellular responses to environmental signals are mediated by two-component signal transduction systems comprising a membrane-associated histidine protein kinase and a cytoplasmic response regulator (RR), which interpret specific stimuli and produce a measured physiological response . In RR activation, transient phosphorylation of a highly conserved aspartic acid residue drives the conformation changes needed for full activation of the protein . Sequence homology reveals that RR02 from Streptococcus pneumoniae belongs to the OmpR subfamily of RRs . The structures of the receiver domains from four members of this family, DrrB and DrrD from Thermotoga maritima, PhoB from Escherichia coli, and PhoP from Bacillus subtilis, have been elucidated . These domains are globally very similar in that they are composed of a doubly wound alpha(5)beta(5); however, they differ remarkably in the fine detail of the beta4-alpha4 and alpha4 regions . The structures presented here reveal a further difference of the geometry in this region . RR02 is has been shown to be the essential RR in the gram-positive bacterium S . pneumoniae R . Lange, C . Wagner, A . de Saizieu, N . Flint, J . Molnos, M . Stieger, P . Caspers, M . Kamber, W . Keck, and K . E . Amrein, Gene 237:223-234, 1999; J . P . Throup, K . K . Koretke, A . P . Bryant, K . A . Ingraham, A . F . Chalker, Y . Ge, A . Marra, N . G . Wallis, J . R . Brown, D . J . Holmes, M . Rosenberg, and M . K . Burnham, Mol . Microbiol . 35:566-576, 2000) . RR02 functions as part of a phosphotransfer system that ultimately controls the levels of competence within the bacteria . Here we report the native structure of the receiver domain of RR02 from serotype 4 S . pneumoniae (as well as acetate- and phosphate-bound forms) at different pH levels . Two native structures at 2.3 A, phased by single-wavelength anomalous diffraction (xenon SAD), and 1.85 A and a third structure at pH 5.9 revealed the presence of a phosphate ion outside the active site . The fourth structure revealed the presence of an acetate molecule in the active site.

Cornea, 2004 Apr, 23(3), 289 - 93
Comparative in vitro activity of levofloxacin, ofloxacin, and ciprofloxacin against ocular streptococcal isolates; Miller D et al.; OBJECTIVE: To determine the in vitro efficacy of levofloxacin, ofloxacin, and ciprofloxacin against Streptococcus pneumoniae and Streptococcus viridans isolates recovered from clinical cases of keratitis and endophthalmitis . METHODS: Streptococcal isolates recovered from keratitis and endophthalmitis cases between 1990 and 2001 were identified and extracted from the Microbiology Data Bank of the Bascom Palmer Eye Institute, Miami, FL . Comparative in vitro minimal inhibitory concentration (MIC90) susceptibility profiles for levofloxacin, ofloxacin, and ciprofloxacin against a select group (n = 65) of streptococcal isolates were documented using the E test methodology . Penicillin susceptibility profiles were also evaluated . chi 2 x 2 tables and McNemar's Paired-Sample Tests were used to established statistical significance . RESULTS: MIC90 values for levofloxacin, ofloxacin, and ciprofloxacin against pneumococcal isolates were 1.5, 6, and 3 microg/mL . The corresponding values for the S . viridans group were 2, 8, and 24 microg/mL . Levofloxacin was 4 times more active in vitro than ofloxacin and 2 times more active in vitro than ciprofloxacin against S . pneumoniae . Levofloxacin was 4 times more active in vitro than ofloxacin and 12 times more active than ciprofloxacin for S . viridans group . Sixty-three percent of the S . pneumoniae and 57.9% of the S . viridans group isolates were intermediate or resistant to penicillin . Levofloxacin provides 100% coverage for penicillin-intermediate and penicillin-resistant isolates versus 33.8% for ofloxacin and 29.2% for ciprofloxacin . CONCLUSION: Levofloxacin is highly active in vitro against streptococcal isolates recovered from keratitis and endophthalmitis patients, including penicillin-intermediate and penicillin-resistant strains.

Chemotherapy, 2004 Apr, 50(1), 11 - 6
Determination of the pharmacodynamic profile of daptomycin against Streptococcus pneumoniae isolates with varying susceptibility to penicillin in a murine thigh infection model; Dandekar PK et al.; BACKGROUND: Daptomycin has demonstrated in vitro activity against gram-positive organisms, including Streptococcus pneumoniae . However, the pharmacodynamic (PD) profile of daptomycin is needed to relate the activity of the drug to biologically achievable concentrations . METHODS: The PD profile of daptomycin against four S . pneumoniae isolates was determined using the immunocompromised murine thigh model . Due to the high protein binding of this agent, PD parameters were calculated based on free drug exposures . Efficacy was assessed by the change in log colony-forming units (CFU) in thighs after 24 h of drug treatment . RESULTS: Daptomycin produced a 7.1 (95% confidence interval 7.0-7.2) log(10) CFU kill . The ratio between overall drug exposure and the minimum inhibitory concentration (MIC) (AUC/MIC) was the most predictive of the PD parameters . The S . pneumoniae AUC/MIC required for static effects was 12 (95% confidence interval 10-14) . Eighty percent and 99% of maximal kill was achieved at ratios of 35 (95% confidence interval 32-39) and 184 (95% confidence interval 160-208), respectively . CONCLUSIONS: Clinically achievable serum drug exposures produced by the lowest dose of daptomycin currently studied in humans (4 mg/kg/day) should result in a potent in vivo bactericidal effect against infections due to S . pneumoniae such as bacteremia, where serum drug concentrations adequately reflect the concentration at the site of infection .

J Formos Med Assoc, 2004 Feb, 103(2), 118 - 23
Bacteremic Streptococcus bovis infections at a university hospital, 1992-2001; Jean SS et al.; BACKGROUND AND PURPOSE: The association of Streptococcus bovis biotypes with types of clinical infection and underlying malignancies has rarely been reported in Taiwan . The aim of this study was to characterize the clinical features and microbiological characteristics of patients with S . bovis bacteremia . METHODS: From January 1992 to December 2001, 62 patients with S . bovis bacteremia were treated at National Taiwan University Hospital . Their demographic characteristics, clinical features, results of imaging studies, pathological findings, and laboratory data were retrospectively analyzed . Antimicrobial susceptibilities were determined using the agar dilution method and biotypes were determined using the API 20 Strep system . RESULTS: The majority of cases (76%) occurred during the 1996-1997 and 1999-2000 periods . Thirty five patients were male, and the mean age of the 62 patients was 61 years . Underlying diseases included malignancies (40%), cardiac diseases (27%), diabetes mellitus (24%), and liver cirrhosis (21%) . Fifty two percent (n = 32) of patients presented with primary bacteremia and 24% (15) with definite or possible infective endocarditis . Thirteen percent (8) presented with hepatobiliary infections (acute cholecystitis and biliary tract infection) . Ten patients (16%) had polymicrobial bacteremia . All of the concomitant pathogen(s) were Gram-negative rods, among which Escherichia coli predominated . The mortality rate on day 30 of illness was 21% . High Acute Physiology and Chronic Health Evaluation (APACHE) II score on the day of positive blood culture was associated with high mortality . Among the 19 patients (31%) who underwent colonoscopy, 9 (47%) had colonic lesions (tubular adenomas or carcinomas) . Of the 26 patients (41%) who underwent echocardiography, 14 (54%) had vegetation in the valves . Of the 47 S . bovis isolates examined for biotypes, 37 (79%) were biotype II (29 of biotype II/2 and 8 of biotype II/1) and 10 (21%) were biotype I . The majority of isolates causing primary bacteremia (92%), hepatobiliary infections (100%) and primary bacterial peritonitis (100%) were biotype II, while 67% of isolates associated with infective endocarditis were biotype I . All isolates were susceptible to penicillin . CONCLUSIONS: Infective endocarditis should be highly suspected in patients with bacteremia due to S . bovis biotype I . Investigations for intra-abdominal foci other than the colon should be undertaken in patients with bacteremia caused by S . bovis biotype II . Due to the increasing number of S . bovis bacteremia patients at the hospital and unknown origins of about 50% of bacteremia cases, the need for colonoscopy and echocardiography in each case and biotyping of each blood isolate should be emphasized.

J Mol Biol, 2004 Apr 30, 338(3), 547 - 58
Crystal structure of Streptococcus suis Dps-like peroxide resistance protein Dpr: implications for iron incorporation; Kauko A et al.; The Dps-like peroxide resistance protein (Dpr) is an aerotolerance and hydrogen peroxide resistance agent found in the meningitis-associated pathogen Streptococcus suis . Dpr is believed to act by binding free intracellular iron to prevent Fenton chemistry-catalysed formation of toxic hydroxyl radicals . The crystal structure of Dpr has been determined to 1.95 A resolution . The final model has an Rcyst value of 18.5% (Rfree = 22.4%) and consists of 12 identical monomers (each of them comprising a four alpha-helix bundle) that form a hollow sphere obeying 23 symmetry . Structural features show that Dpr belongs to the Dps family of bacterial proteins . Twelve putative ferroxidase centers, each formed at the interface of neighboring monomer pairs, were identified in the Dpr structure with structural similarities to those found in other Dps family members . Dpr was crystallized in the absence of iron, hence no bound iron was found in the structure in contrast to other Dps family members . A novel metal-binding site approximately 6A from the ferroxidase centre was identified and assigned to a bound calcium ion . Two residues from the ferroxidase centre (Asp63 and Asp74) were found to be involved in calcium binding . Structural comparison with other family members revealed that Asp63 and Asp74 adopt different conformation in the Dpr structure . The structure of Dpr presented here shows potential local conformational changes that may occur during iron incorporation . A role for the metal-binding site in iron uptake is proposed.

J Neuroimmunol, 2004 May, 150(1-2), 157 - 62
Increased serum concentrations of monokine induced by interferon-gamma/CXCL9 and interferon-gamma-inducible protein 10/CXCL-10 in Sydenham's chorea patients; Teixeira AL Jr et al.; Sydenham's chorea (SC) is thought to result from the action of streptococcus-induced antibodies that cross react with basal ganglia antigens . Much less is known, however, about the involvement of cellular mechanisms in its pathogenesis . Since chemokines seem to play a role in several CNS inflammatory disorders, we sought to investigate the chemokine profile of patients with SC . Increased serum levels of CXCL9, formerly monokine induced by interferon-gamma (Mig), and CXCL10, formerly interferon-gamma-inducible protein of 10 kDa (IP-10) were demonstrated in acute SC patients, suggesting that a particular group of chemokines may be involved in SC pathogenesis.

Int J Pediatr Otorhinolaryngol, 2004 May, 68(5), 585 - 7
Orbital abscess caused by Fusobacterium necrophorum; Pitkaranta A et al.; We report the case of previously healthy boy with orbital abscess secondary to sinusitis . Fusobacterium necrophorum and Streptococcus anginosus was cultured both from the maxillary sinus and the orbital abscess . After surgical drainage and intravenous antibiotic treatment the boy recovered without complications.

Int J Antimicrob Agents, 2004 Apr, 23(4), 377 - 81
Isopanduratin A from Kaempferia pandurata as an active antibacterial agent against cariogenic Streptococcus mutans; Hwang JK et al.; An antibacterial compound active against Streptococcus mutans was isolated from Kaempferia pandurata and identified as isopanduratin A using 1H NMR, 13C NMR and EI-MS . The minimum inhibitory concentration (MIC) of isopanduratin A was 4 mg/l which was much lower than that of some other natural anticariogenic agents such as sanguinarine (12 mg/l), green tea extract and carvacrol (125 mg/l), thymol (250 mg/l) and isoeugenol and eucalyptol (500 mg/l) . The bactericidal test showed that isopanduratin A completely inactivated S . mutans at 20 mg/l in 1 min . Significant inhibitory activity of isopanduratin A was also observed against S . sobrinus, S . sanguinis and S . salivarius with an MIC of 4 mg/l . Damage to the cell membrane and cell wall of S . mutans by isopanduratin A was shown using transmission electron microscopy (TEM) . These results suggest that isopanduratin A could be employed as a potential antibacterial agent for preventing dental caries.

Int J Antimicrob Agents, 2004 Apr, 23(4), 337 - 42
Reassessment of the cefaclor breakpoint for Streptococcus pneumoniae; MacKenzie FM et al.; Discrepancies between proven clinical success of cefaclor and its relatively poor activity in vitro were investigated against eight pneumococcal isolates . The bacteriostatic minimum inhibitory concentration (MIC) (the concentration resulting in no growth/kill relative to the starting inoculum) was derived from time kill studies . Bioassay results demonstrated an in vitro half-life of >24 and 9 h for cefuroxime and cefaclor, respectively . The mean NCCLS MIC for cefaclor was 1.4 and 0.3 mg/l for cefuroxime . The corresponding mean bacteriostatic MICs were 0.24 and 0.16 mg/l . Whilst cefaclor NCCLS MICs were significantly higher compared with cefuroxime MICs (P = 0.00058) there was no statistical differences between the bacteriostatic MICs (P = 0.259) . Bacteriostatic MIC determination established that cefaclor and cefuroxime are equally active against pneumococci.

Pediatr Dent, 2004 Jan-Feb, 26(1), 5 - 10
Effect of povidone-iodine on Streptococcus mutans in children with extensive dental caries; Amin MS et al.; PURPOSE: The purpose of this pilot project was to determine the effect of a 10% povidone-iodine solution on plaque Streptococcus mutans and on incidence of new caries in young children following dental rehabilitation under general anesthesia . METHODS: Twenty-five children ages 2 to 7 years, scheduled for dental treatment under general anesthesia, were enrolled . Children in the experimental group (N = 13) had povidone-iodine applied 3 times at 2-month intervals . Control children (N = 12) had no treatment . Plaque samples were taken from all children at baseline, 6 months and cultured for total bacteria and S mutans . Dental examinations were conducted at baseline, 6 months, and 1 year . RESULTS: Experimental and control children had similar dietary habits, caries experience, and S mutans levels at baseline . All children's S mutans counts decreased significantly at 6 months (P = .003) . The difference between the 2 groups was not significant (P = .58) . At 1 year, 5 of 8 children in the control group had new caries compared to 2 of 11 children in the experimental group (P = .06) . Povidone-iodine was well accepted by participating families . CONCLUSIONS: Extensive one-time restorative dental treatment resulted in a significant suppression S mutans levels at 6 months . Further exploration of the role of povidone-iodine in caries management is indicated.

Chest, 2004 Apr, 125(4), 1343 - 51
Viral community-acquired pneumonia in nonimmunocompromised adults; de Roux A et al.; INTRODUCTION: Viral community-acquired pneumonia (CAP) has been poorly studied and clinically characterized . Using strict criteria for inclusion, we studied this type of infection in a large series of hospitalized adults with CAP . MATERIALS AND METHODS: All nonimmunocompromised adult patients with a diagnosis of CAP having paired serology for respiratory viruses (RVs) {338 patients} were prospectively included in the study from 1996 to 2001 at our 1,000-bed university teaching hospital, and subsequently were followed up . We compared patients with pure viral (PV), mixed viral (RV + bacteria), and pneumococcal CAP . RVs (ie, influenza, parainfluenza, respiratory syncytial virus, and adenovirus) were diagnosed by means of paired serology . RESULTS: Sixty-one of 338 patients (18%) with paired serology had an RV detected, and in 31 cases (9%) it was the only pathogen identified . Influenza was the most frequent virus detected (39 patients; 64%) . Patients with chronic heart failure (CHF) had an increased risk of acquiring PV CAP (8 of 26 patients; 31%) when compared to a mixed viral/bacterial etiology (2 of 26 patients; 8%; p = 0.035) or CAP caused by Streptococcus pneumoniae (1 of 44 patients; 2%; p = 0.001) . Multivariate analysis revealed that CHF (odds ratio {OR}, 15.3; 95% confidence interval {CI}, 1.4 to 163; p = 0.024) and the absence of expectoration (OR, 0.14; 95% CI, 0.04 to 0.6; p = 0.006) were associated with PV pneumonia compared to pneumococcal CAP . CONCLUSION: RVs are frequent etiologies of CAP (single or in combination with bacteria) . Patients with CHF have an increased risk of acquiring a viral CAP.

Chest, 2004 Apr, 125(4), 1335 - 42
Contribution of C-reactive protein to the diagnosis and assessment of severity of community-acquired pneumonia; Almirall J et al.; STUDY OBJECTIVE: To assess the usefulness of serum C-reactive protein (CRP) in the diagnosis and treatment approach of patients with community-acquired pneumonia (CAP) . DESIGN: Population-based case-control study . SETTING: A mixed residential-industrial urban area of 74,368 adult inhabitants in the Maresme region (Barcelona, Spain) . PATIENTS: From December 1993 to November 1995, all subjects who were > 14 years of age, were living in the area, and had received a diagnosis of CAP, which had been confirmed by chest radiographs and compatible clinical outcome, were registered . Patients from residential care facilities were excluded . Serum samples were assayed for CRP in the acute phase of the disease . Data from 201 patients with CAP were compared with 84 healthy control subjects matched by age, sex, and municipality, as well as with 25 patients with initially suspected pneumonia that was not confirmed at follow-up . Median CRP levels were 110.7, 1.9, and 31.9 mg/L, respectively . The thresholds of the test for discriminating among these three groups of subjects were 11.0 and 33.15 mg/L . RESULTS: Eighty-nine patients (44.8%) had an identifiable etiology . The most common pathogens were Streptococcus pneumoniae, viruses, and Chlamydia pneumoniae, followed by Mycoplasma pneumoniae, Legionella pneumophila, and Coxiella burnetii . There were statistically significant differences in the median CRP levels in pneumococcal (166.0 mg/L) and L pneumophila (178.0 mg/L) etiologies compared to other causative pathogens . Lower levels of CRP were found in pneumonia caused by viruses and C burnetii as well as in negative microbiological findings . The median CRP levels in hospitalized patients were significantly higher than in outpatients (132.0 vs 76.9 mg/L, respectively; p < 0.001) . Considering a cut point of 106 mg/L in men and 110 mg/L in women for deciding about the appropriateness of inpatient care, CRP levels showed a sensitivity of 80.51% and a specificity of 80.72% . CONCLUSIONS: Serum CRP level is a useful marker for establishing the diagnosis of CAP in adult patients with lower respiratory tract infections . High CRP values are especially high in patients with pneumonias caused by S pneumoniae or L pneumophila . Moreover, high CRP values are suggestive of severity, which may be of value in deciding about the appropriateness of inpatient care.

Emerg Infect Dis, 2004 Jan, 10(1), 54 - 9
Hospital-reported pneumococcal susceptibility to penicillin; Metlay JP et al.; Geographic variation in drug susceptibility among isolates of Streptococcus pneumoniae has influenced national treatment guidelines for community-acquired pneumonia . Whether individual hospital susceptibility data provide reliable and valid information for providers is unclear . We examined the geographic and temporal variability in hospital-reported rates of pneumococcal susceptibility . We surveyed all 52 hospitals that provided acute adult care in the five counties surrounding Philadelphia and collected data on levels of penicillin susceptibility among all pneumococcal blood isolates from 1998 to 2000 . In 1998, pneumococcal nonsusceptibility to penicillin varied from 0% to 67% of all blood isolates across the 33 hospitals with >10 isolates in that year . Hospital location did not correlate with the level of reported pneumococcal susceptibility (p = 0.8) . In addition, correlations were not significant in reported pneumococcal susceptibility to penicillin within individual hospitals during the 3 years.

J Chemother, 2004 Feb, 16(1), 56 - 61
Serum bactericidal activity of gemifloxacin versus clarithromycin against Streptococcus pneumoniae with different susceptibility to quinolones; Malerczyk C et al.; The objective of this study was to determine serum bactericidal titers (SBT, the highest dilution of serum showing no growth) and the serum bactericidal activity (SBA, i.e . duration of SBT greater than 1:2) as well as the serum bactericidal rate of gemifloxacin and clarithromycin after single doses in healthy male volunteers against Streptococcus pneumoniae . Strains tested had various degrees of susceptibility to penicillin as well as different susceptibility to quinolones due to a different QRDR mutation pattern (parC, gyrA) . Serum samples from volunteers (n = 12) who had received a single oral dose of either 320 mg gemifloxacin or 500 mg clarithromycin in an open-label crossover study were obtained over a 24-hour period . SBA was determined, using the microdilution method . SBA of wildtype strains for gemifloxacin ranged from 8.9 to 15.4 h (mean 12.6 h) . For gemifloxacin, 2 strains with solitary gyrA mutation had an SBA from 4.5 to 4.7 h (median 4.5 h) . One of the 2 strains with a single QRDR mutation in parC displayed an SBA of 4.5 h, comparable to the gyrA mutation strains, whereas the second strain had a nearly twice as long SBA of 8.9 h . Two strains with two mutations (parC and gyrA) did not display any SBA . For clarithromycin, the duration of SBA ranged from 11.3 to 15.5 h (mean 13.6 h) for 6 of the 12 strains with an MIC < or = 0.06 mg/L (no SBA was found for the remaining strains, with an MIC of 0.25 mg/L or higher) . In conclusion, a correlation between individual serum concentrations and SBA was found for both antibiotics.

J Chemother, 2004 Feb, 16(1), 13 - 22
Comparative activity of telithromycin against macrolide-resistant isolates of Streptococcus pneumoniae: results of two years of the PROTEKT surveillance study; Schito GC et al.; The increase in resistance to macrolides has been linked with increasing use of these agents as empirical therapy for community-acquired respiratory tract infections (CARTIs) . As part of the ongoing PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) surveillance program, over 7600 Streptococcus pneumoniae isolates were collected worldwide from 1999-2001 and evaluated for macrolide resistance . Globally, macrolide resistance was 31-33%, with considerable inter-country variation (<10-88%) and particularly high prevalence in the Far East (>71%) . In Europe, France had the most resistant isolates (>53%) . The highest rates of macrolide resistance were seen in 0-2 year olds . Co-resistance to clindamycin (64%) and all beta-lactams (14-79%) was seen among macrolide-resistant isolates, but >99% of these isolates were susceptible to telithromycin, vancomycin and linezolid . There was considerable variation in the prevalence of erm(B) (56-64%) and mef(A) (30-35%): erm(B) was prevalent in Europe and mef(A) in North America . Globally, 5-7% isolates carried both mechanisms (erm(B)+mef(A)); of these, 47-65% were from South Korea . These double resistance isolates were >90% resistant to the beta-lactams, except amoxicillin-clavulanate . Clindamycin was active against >98% mef(A) but poorly active against erm(B) and erm(B)+mef(A) isolates . Telithromycin, vancomycin and linezolid were highly active (>99.5%) across all three genotypes . CONCLUSIONS: In vitro, telithromycin, vancomycin and linezolid are highly active against antibiotic-resistant strains of S . pneumoniae . Telithromycin may be a useful therapeutic alternative to macrolides for the treatment of CARTIs.

J Pediatr Orthop B, 2004 Mar, 13(2), 114 - 7
Septic arthritis of the elbow after chickenpox; Konyves A et al.; Musculoskeletal complications following chickenpox are rare among immunologically normal children . Septic arthritis after varicella is caused by group A Streptococcus and affects the knee most frequently . We present a case of septic arthritis of the elbow caused by Staphylococcus aureus . We review the English language literature on septic arthritis complicating chickenpox . We conclude that diagnosis and treatment should be carried out according to guidelines on de novo septic arthritis including the early use of magnetic resonance imaging.

Acta Vet Scand, 2003, 44(3-4), 131 - 43
Assessment of early postpartum reproductive performance in two high producing Estonian dairy herds; Kask K et al.; Early postpartum (6 weeks) ovarian activity, hormonal profiles, uterine involution, uterine infections, serum electrolytes, glucose, milk acetoacetate and blood urea nitrogen (BUN) levels were studied in 2 Estonian high producing dairy herd with annual milk production of 7688 (Farm A) and 9425 (Farm B) . From each farm 10 cows, with normal calving performance were used . Blood samples for the hormonal (PGF2alpha-metabolite, progesterone) analyses were withdrawn . On day 25 PP blood serum samples were taken for the evaluation of metabolic/electrolyte status . On the same day estimation of milk acetoacetate values was done . The ultrasound (US) was started on day 7 PP and was performed every 3rd day until the end of experiment . Uterine content, follicular activity and sizes of the largest follicle and corpus luteum were monitored and measured . Vaginal discharge and uterine tone were recorded during the rectal palpation . Each animal in the study was sampled for bacteriological examination using endometrial biopsies once a week . Two types of PGF2alpha-metabolite patterns were detected: elevated levels during 14 days PP, then decline to the basal level and then a second small elevation at the time of final elimination of the bacteria from the uterus: or elevated levels during first 7 days PP, then decline to the basal level and a second small elevation before the final elimination of bacteria . Endometritis was diagnosed in 5 cows in farm A and in 3 cows in farm B respectively . In farm A, 5 cows out of 10 ovulated during experimental period and in 1 cow cystic ovaries were found . In farm B, 3 cows out of 10 ovulated . In 3 cows cystic ovaries were found . Altogether 40% of cows had their first ovulation during the experimental period . Three cows in farm A and 5 cows in farm B were totally bacteria negative during the experimental period . The most frequent bacteria found were A . pyogenes, Streptococcus spp., E . coli., F . necrophorum and Bacteroides spp . The highest incidence of bacteriological species was found during the first 3 weeks in both farms . All animals were free from bacteria after 5th week PP in farm A and after 4th week in farm B respectively . Serum electrolytes and glucose levels were found to be within the reference limits for the cows in both farms . No significant difference was found between farms (p > 0.05) . Low phosphorus levels were found in both farms . Significant difference (p < 0.05) was found in BUN levels between farms . In both farms milk acetoacetate values were staying within the reference range given for the used test (< 100 micromol/l) . The uterine involution and bacterial elimination in the investigated cows could consider as normal but more profound metabolic studies could be needed to find reasons for later resumption of ovarian activity . Some recommendations to changing feeding regimes and strategies should also be given.

Microbiology, 2004 Apr, 150(Pt 4), 1015 - 22
Relations between macroscopic and microscopic adhesion of Streptococcus mitis strains to surfaces; Vadillo-Rodriguez V et al.; Application of physico-chemical models to describe bacterial adhesion to surfaces has hitherto only been partly successful due to the structural and chemical heterogeneities of bacterial surfaces, which remain largely unaccounted for in macroscopic physico-chemical characterizations of the cell surfaces . In this study, the authors attempted to correlate microscopic adhesion of a collection of nine Streptococcus mitis strains to the negatively charged, hydrophilic silicon nitride tip of an atomic force microscope (AFM) with macroscopic adhesion of the strains to a negatively charged, hydrophilic glass in a parallel-plate flow chamber . The repulsive force probed by AFM upon approach of the tip to a bacterial cell surface ranged from 1.7 to 7.7 nN depending on the strain considered and was found to correspond to an activation barrier, governing initial, macroscopic adhesion of the organisms to the glass surface . Moreover, maximum distances at which attractive forces were probed by the AFM upon retraction of the tip (120 to 1186 nm) were related to the area blocked by an adhering bacterium, i.e . the distance kept between adhering bacteria . Bacterial desorption could not be related to adhesive forces as probed by the AFM, possibly due to the distinct nature of the desorption process occurring in the parallel-plate flow chamber and the forced detachment in AFM.

J Antimicrob Chemother, 2004 May, 53(5), 826 - 31 Epub 2004 Apr 08.
Prospective surveillance of incidence, serotypes and antimicrobial susceptibility of invasive Streptococcus pneumoniae among hospitalized children in Austria; Rendi-Wagner P et al.; OBJECTIVES: This study was undertaken to analyse incidence rates, serotype distribution and antimicrobial resistance patterns of invasive Streptococcus pneumoniae isolates from hospitalized children up to 5 years of age with invasive pneumococcal disease (IPD), including meningitis, in Austria . METHODS: From February 2001-January 2003, nationwide prospective surveillance was conducted that included all paediatric hospitals and clinical microbiological laboratories . All invasive pneumococci isolated were serotyped and tested for antimicrobial susceptibility . RESULTS: The mean annual incidence rates of IPD per 10 000 population for the age groups <24 months and <60 months were 14.5 (7.7 for meningitis) and 13.7 (6.0 for meningitis), respectively . The case fatality rate was 6% for IPD and 12% for meningitis . Of all IPD cases, 69.6% (73.1% for meningitis) were covered by serotypes and 83.9% (88.5% for meningitis) by cross-protection of vaccine-related serotypes . Intermediate penicillin G susceptibility (MIC 0.12-1 mg/L) was found in 12/56 strains . No penicillin G-resistant strains were found . A total of 19/56 isolates showed decreased susceptibility to macrolide agents (MIC >/= 1 mg/L) . CONCLUSIONS: The IPD incidence rate was similar, and serotype coverage of the 7-valent conjugated vaccine marginally superior, to Germany . The surprisingly high level of antimicrobial resistance among invasive isolates considerably amplifies the potential impact of a childhood pneumococcal vaccination programme in Austria.

Community Dent Health, 2004 Mar, 21(1 Suppl), 71 - 85
Risk factors for dental caries in young children: a systematic review of the literature; Harris R et al.; OBJECTIVE: To conduct a systematic review of the literature on risk factors for dental caries in deciduous teeth of children aged six years and under, to give a scientific framework for the international collaborative studies on inequalities in childhood caries . METHOD: Accepted guidelines were followed . Studies were identified by electronic searching and reviewed on the basis of key words, title and abstract by two reviewers to assess whether inclusion criteria were met . Copies of all articles were obtained and assessed for quality according to the study design . RESULTS: 1029 papers were identified from the electronic search, 260 met the prima facie inclusion criteria . 183 were excluded once full copies of these papers were obtained . Of the 77 studies included, 43 were cross sectional, 19 cohort studies, 8 case control studies and 7 interventional studies . Few obtained the highest quality scores . 106 risk factors were significantly related to the prevalence or incidence of caries . CONCLUSION: There is a shortage of high quality studies using the optimum study design, i.e . a longitudinal study . The evidence suggests that children are most likely to develop caries if Streptococcus Muttans is acquired at an early age, although this may be partly compensated by other factors such as good oral hygiene and a non-cariogenic diet . Diet and oral hygiene may interact so that if there is a balance of 'good' habits by way of maintaining good plaque control and 'bad' habits by way of having a cariogenic diet, the development of caries may be controlled.

Crit Care Med, 2004 Apr, 32(4), 992 - 7
Severe bloodstream infections: a population-based assessment; Laupland KB et al.; OBJECTIVE: Although bloodstream infection commonly results in critical illness, population-based studies of the epidemiology of severe bloodstream infection are lacking . We sought to define the incidence and microbiology of severe bloodstream infection (bloodstream infection associated with intensive care unit admission within 48 hrs) and assess risk factors for acquisition and death . DESIGN: Population-based surveillance cohort . SETTING: Multidisciplinary and cardiovascular surgical intensive care units . PATIENTS: All adults with severe bloodstream infection in the Calgary Health Region (population approximately 1 million) during 2000-2002 . INTERVENTIONS: None . MEASUREMENTS AND MAIN RESULTS: Three hundred forty patients had 342 episodes of severe bloodstream infection (15.7 per 100,000 population/year) . Several demographic and chronic conditions were significant risk factors for acquiring severe bloodstream infection (relative risk, 95% confidence interval) including age > or =65 yrs (7.0, 5.6-8.7), male gender (1.3, 1.1-1.6), urban residence (2.4, 1.2-5.6), hemodialysis (208.7, 142.9-296.3), diabetes mellitus (5.9, 4.4-7.8), alcoholism (5.6, 3.8-8.0), cancer (7.5, 5.3-10.3), and lung disease (3.8, 2.6-5.4) . The most common etiologies were Staphylococcus aureus, Escherichia coli, and Streptococcus pneumoniae (3.0, 3.0, and 1.9 per 100,000/year, respectively) . The case-fatality rate was 142 of 340 (42%) for an annual mortality rate of 6.5 per 100,000 . Increased Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.1 per point; 95% confidence interval, 1.1-1.2) and presence of a comorbidity (odds ratio, 2.5; 95% confidence interval, 1.4-4.3) were significant independent predictors of death . CONCLUSIONS: Bloodstream infections are commonly severe enough to require management in an intensive care unit and are associated with a high mortality rate . Identification of risk factors for severe bloodstream infection may allow targeting of preventive efforts to individuals at greatest potential benefit.

Pediatr Infect Dis J, 2004 Apr, 23(4), 371 - 3
Pneumococcal psoas pyomyositis associated with complement deficiency; Tuerlinckx D et al.; A 4.5-year-old boy with complement deficiency developed infection of the psoas caused by Streptococcus pneumoniae . Pyomyositis of the psoas muscle is uncommon but should be included in the differential diagnosis of fever and lameness . The most useful diagnostic test is computed tomography guided needle aspiration, and underlying conditions should be sought.

Pediatr Infect Dis J, 2004 Apr, 23(4), 295 - 9
Neonatal early onset Escherichia coli sepsis: trends in incidence and antimicrobial resistance in the era of intrapartum antimicrobial prophylaxis; Alarcon A et al.; BACKGROUND: Although intrapartum antimicrobial prophylaxis has lowered the incidence of early onset group B Streptococcus (GBS) sepsis, there are concerns that the increased use of antibiotics may raise the incidence of non-GBS antimicrobial-resistant infections . The objective of this study was to determine trends in the incidence and antimicrobial resistance of early onset sepsis caused by Escherichia coli in the era of antimicrobial prophylaxis . METHODS: All neonates with early onset E . coli infection who were born at La Paz Hospital, Madrid, from January 1, 1992, through December 31, 2002, were identified from a microbiologic register of all neonatal infections . To evaluate the effect of the guidelines for GBS prevention, data were pooled and compared for: 1992 through 1995 (Period 1); 1996 through 1998 (Period 2); and 1999 through 2002 (Period 3) . RESULTS: Early onset E . coli infection was diagnosed in 41 of 84 612 live births . The infection rate did not change significantly during the 3 time periods (0.56, 0.24 and 0.55 per 1000 during Periods 1, 2 and 3, respectively; P = 0.936, linear-by-linear association) . The proportion of E . coli infections that were resistant to ampicillin increased significantly among preterm infants, from 25% (1 of 4) in Period 1, to 100% (2 of 2) in Period 2 and to 91% (10 of 11) in Period 3 (P = 0.017, linear-by-linear association), but not among term infants, with 67% (8 of 12) in Period 1, 50% (1 of 2) in Period 2 and 44% (4 of 5) in Period 3 (P = 0.317, linear-by-linear association) . CONCLUSIONS: Although the incidence of early onset sepsis caused by E . coli remained stable during the study period, antibiotic-resistant E . coli infections increased among preterm infants . On the whole these trends are reassuring with respect to GBS prophylaxis . However, the increase in the proportion of ampicillin-resistant infections in preterm infants suggests that continuing evaluation of the risks and benefits of prophylaxis in this group is critical.

Pediatr Res . 2004 Apr 7; {Epub ahead of print}
Defective Neutrophil Oxidative Burst in Preterm Newborns on Exposure to Coagulase-Negative Staphylococci; Bjorkqvist M et al.; The neutrophil oxidative burst is a product of the regulated assembly of the multicomponent oxidase enzyme . Our aim was to compare the oxidative burst in term (n = 10) and preterm newborns <31 wk gestational age (n = 10) after stimulation with coagulase-negative staphylococci in vitro . Strains of Streptococcus epidermidis with different invasive and slime-producing properties, one strain of S . haemolyticus, and one strain of group B-streptococcus were investigated . A whole-blood flow cytometric assay using the oxidation of hydroethidine to ethidium bromide was used . The oxidative activity in unstimulated neutrophil granulocytes {polymorphonuclear leukocytes (PMNLs)} was similar in term and preterm newborns, but the preterm newborns showed a significantly lower capacity to up-regulate the oxidative burst intensity after bacterial stimulation (p = 0.004) . In the term but not in the preterm group, the oxidative burst intensity after bacterial stimulation correlated with the baseline oxidative burst intensity . After bacterial stimulation, there was a trend toward a greater percentage of activated neutrophils in the term group than in the preterm group, but the difference was less pronounced than that in oxidative burst intensity . Significant differences in oxidative burst response to different bacterial strains were observed (p < 0.001), but the differences could not be correlated exclusively to invasive capacity or slime-producing properties . It is concluded that the baseline oxidative activity is similar in term and preterm PMNLs but that preterm PMNLs have a decreased capacity to increase the oxidative burst in response to bacterial stimulation.

J Clin Microbiol, 2004 Apr, 42(4), 1826 - 8
Mycotic Aneurysm Caused by Streptococcus constellatus subsp . constellatus; Chiang WC et al.; An infected mycotic aneurysm due to Streptococcus constellatus subsp . constellatus has not previously been reported . We report on this condition in an 87-year-old woman who had aggravating abdominal pain and a large fusiform aneurysm over the thoracic-abdominal aorta with mural thrombus . Isolates from two sets of blood cultures and the debrided tissue were identified as S . constellatus subsp . constellatus by their biochemical reaction profiles, compatible 16S rRNA gene sequencing results, and sequencing results for the partial groESL gene and the 16S-23S intergenic spacer region.

J Clin Microbiol, 2004 Apr, 42(4), 1746 - 50
Unique variations of pbp2b sequences in penicillin-nonsusceptible Streptococcus pneumoniae isolates from Korea; Baek JY et al.; pbp2b gene alterations were analyzed in 102 clinical isolates of Streptococcus pneumoniae (30 penicillin susceptible, 23 intermediate, and 49 resistant) from Korea . On the basis of PBP2B amino acid sequences, penicillin-nonsusceptible isolates of S . pneumoniae belonged to six groups, and 76% of the isolates in groups I to IV showed the same divergent block of amino acid alterations . Thirteen isolates (group II) also possessed a divergent block that was identical to that of Streptococcus oralis . The pbp2b genes of most Korean isolates showed novel mosaic mutations due to horizontal gene transfer . The Thr252 --> Ala substitution, previously thought to be associated only with penicillin-nonsusceptible strains, was also found in three penicillin-susceptible strains . On the basis of their pbp2b nucleotide sequences, all penicillin-nonsusceptible isolates can be detected by multiplex PCR, which can be used as a novel method for detection of antibiotic-resistant pneumococcal strains in clinical specimens.

J Clin Microbiol, 2004 Apr, 42(4), 1596 - 600
Immunoblot method to detect Streptococcus pneumoniae and identify multiple serotypes from nasopharyngeal secretions; Bronsdon MA et al.; Conventional culture techniques are limited in the ability to detect multiple Streptococcus pneumoniae serotypes in nasopharyngeal (NP) secretions . We developed an immunoblot (IB) method with monoclonal antibodies (MAbs) to detect S . pneumoniae and to identify serotypes . NP specimens stored in skim milk-tryptone-glucose-glycerol medium were assessed by the IB method and the reference culture method (RM) . In the RM, four optochin-sensitive alpha-hemolytic colonies resembling pneumococci were typed by the Quellung reaction . In the IB method, a nitrocellulose membrane blot of surface growth was reacted with a pneumococcal surface adhesion (PsaA) MAb and visualized . Of 47 NP specimens, 32 (68%) were found to be positive and 13 (28%) were found to be negative for pneumococci by both methods; each method alone yielded one positive result . The sensitivity and specificity of the IB method for the detection of pneumococci were 97 and 93%, respectively . To identify serotypes, blots were tested with serotype-specific MAbs (4, 6A, 6B, 9V, 14, 18C, 19F, and 23F) . To detect the remaining serotypes, positive serotype-specific replicate blots were compared visually to an original anti-PsaA-positive blot; four unidentified colonies were subcultured and serotyped by the Quellung reaction . Fifty-eight S . pneumoniae-positive NP specimens containing 69 pneumococcal strains (23 serotypes) were tested; 68 (98.6%) of the strains were detected by the IB method, and 66 (95.6%) were detected by the RM . For 11 specimens found to contain two serotypes, both methods detected both serotypes in 7 (63.6%), the IB method alone detected the two serotypes in 3 (27.3%), and the RM alone detected both serotypes in 1 (9%) . The IB method identified multiple clones and minor populations of pneumococci in NP secretions . This method is useful for detecting specific serotypes and carriage of multiple serotypes in epidemiologic surveillance and carriage studies.

J Clin Microbiol, 2004 Apr, 42(4), 1559 - 63
Detection of multiple macrolide- and lincosamide-resistant strains of Streptococcus pyogenes from patients in the Boston area; Hasenbein ME et al.; Macrolide (including erythromycin and azithromycin) and lincosamide (including clindamycin) antibiotics are recommended for treatment of penicillin-allergic patients with Streptococcus pyogenes pharyngitis . Resistance to erythromycin in S . pyogenes can be as high as 48% in specific populations in the United States . Macrolide and lincosamide resistance in S . pyogenes is mediated by several different genes . Expression of the erm(A) or erm(B) genes causes resistance to erythromycin and inducible or constitutive resistance to clindamycin, respectively, whereas expression of the mef(A) gene leads to resistance to erythromycin but not clindamycin . We studied the resistance of S . pyogenes to erythromycin and clindamycin at an urban tertiary-care hospital . Of 196 sequential isolates from throat cultures, 15 (7.7%) were resistant to erythromycin . Three of these were also constitutively resistant to clindamycin and had the erm(B) gene . Five of the erythromycin-resistant isolates were resistant to clindamycin upon induction with erythromycin and had the erm(A) gene . The remaining seven erythromycin-resistant isolates were susceptible to clindamycin even upon induction with erythromycin and had the mef(A) gene . Pulsed-field gel electrophoresis analysis and emm typing demonstrated that the erythromycin-resistant S . pyogenes comprised multiple strains . These results demonstrate that multiple mechanisms of resistance to macrolide and lincosamide antibiotics are present in S . pyogenes strains in the United States.

J Pediatr, 2004 Apr, 144(4), 512 - 8
Primary immunodeficiency to pneumococcal infection due to a defect in Toll-like receptor signaling; Currie AJ et al.; OBJECTIVE: The role of human Toll-like receptors (TLRs) in initiating protective immune responses in vivo is not well understood . We investigated the role of TLR signaling in defense against infection in a 3-year-old boy with a severe defect resulting in recurrent Streptococcus pneumoniae bacteremia . METHODS: After classic immunodeficiencies were ruled out, the patient's mononuclear cells, macrophages, and dendritic cells (DCs) were studied . TLR signaling responses to a range of TLR- and interleukin-1 receptor (IL-1R)-specific agonists were investigated pre- and posttranscriptionally by measuring NF-kappaB translocation and cytokine mRNA and protein expression . RESULTS: The patient's monocytic cells were profoundly deficient in cytokine production in response to a range of microbial-derived TLR agonists and to recombinant IL-1beta or IL-18 . Lipopolysaccharide (LPS)-induced translocation of NF-kappaB p50 and p65 and the kinetics of LPS-induced cytokine mRNA transcription were normal except for IL-6 and IL-12p40, which were poorly transcribed . Despite deficient responses to TLR agonists by the patient's DCs and B cells, CD40L responses were normal . CONCLUSIONS: We describe a patient with deficient TLR-mediated cytokine production with intact interleukin receptor-associated kinase (IRAK)-4 expression, NF-kappaB translocation, and enhanced susceptibility to infection . This patient demonstrates that TLR signaling, in the presence of intact antibody responses, may be a nonredundant requirement for defense against pyogenic infections.

JAMA, 2004 Apr 7, 291(13), 1587 - 95
Empirical validation of guidelines for the management of pharyngitis in children and adults; McIsaac WJ et al.; CONTEXT: Recent guidelines for management of pharyngitis vary in their recommendations concerning empirical antibiotic treatment and the need for laboratory confirmation of group A streptococcus (GAS) . OBJECTIVE: To assess the impact of guideline recommendations and alternative approaches on identification and treatment of GAS pharyngitis in children and adults . DESIGN, SETTING, AND PARTICIPANTS: Throat cultures and rapid antigen tests were performed on 787 children and adults aged 3 to 69 years with acute sore throat attending a family medicine clinic in Calgary, Alberta, from September 1999 to August 2002 . Recommendations from 2 guidelines (those of the Infectious Diseases Society of America and of the American College of Physicians-American Society of Internal Medicine/American Academy of Family Physicians/US Centers for Disease Control and Prevention) were compared with rapid testing alone, a clinical prediction rule (ie, the modified Centor score), and a criterion standard of treatment for positive throat culture results only . MAIN OUTCOME MEASURES: Sensitivity and specificity of each strategy for identifying GAS pharyngitis, total antibiotics recommended, and unnecessary antibiotic prescriptions . RESULTS: In children, sensitivity for streptococcal infection ranged from 85.8% (133/155; 95% confidence interval {CI}, 79.3%-90.0%) for rapid testing to 100% for culturing all . In adults, sensitivity ranged from 76.7% (56/73; 95% CI, 65.4%-85.8%) for rapid testing without culture confirmation of negative results to 100% for culturing all . In children, specificity ranged from 90.3% (270/299; 95% CI, 86.4%-93.4%) for use of modified Centor score and throat culture to 100% for culturing all . In adults, specificity ranged from 43.8% (114/260; 95% CI, 37.7%-50.1%) for empirical treatment based on a modified Centor score of 3 or 4 to 100% for culturing all . Total antibiotic prescriptions were lowest with rapid testing (24.7% {194/787}; 95% CI, 21.7%-27.8%) and highest with empirical treatment of high-risk adults (45.7% {360/787}; 95% CI, 42.2%-49.3%), due to a high rate of unnecessary prescriptions in adults (43.8% {146/333}; 95% CI, 38.4%-49.4%) . CONCLUSIONS: Guideline recommendations for the selective use of throat cultures but antibiotic treatment based only on positive rapid test or throat culture results can reduce unnecessary use of antibiotics for treatment of pharyngitis . However, empirical treatment of adults having a Centor score of 3 or 4 is associated with a high rate of unnecessary antibiotic use . In children, strategies incorporating throat culture or throat culture confirmation of negative rapid antigen test results are highly sensitive and specific . Throat culture of all adults or those selected on the basis of a clinical prediction rule had the highest sensitivity and specificity.

Vaccine, 2004 Apr 16, 22(13-14), 1717 - 27
DNA vaccination in utero: a new approach to induce protective immunity in the newborn; Gerdts V et al.; Infectious diseases are the primary cause of neonatal morbidity and mortality in people, resulting in millions of deaths every year . Infection of the newborn with some of the pathogens involved, such as herpes simplex virus (HSV), human immunodeficiency virus (HIV), hepatitis B virus (HBV), human cytomegalovirus (HCMV) or group B Streptococcus sp . (GBS), usually occurs at the end of pregnancy, during birth or by breast feeding . Therefore, active immunization of the fetus might represent an effective approach to reduce the high risk of neonatal diseases . We recently showed that DNA immunization in utero within the third trimester of gestation induced strong humoral and cell-mediated immune responses in immunized fetal lambs . Here, we demonstrate that fetal immunization was safe and did not affect fetal gestation, neonatal viability, or significantly alter blood leukocyte populations . In utero immunization resulted in the induction of protective mucosal immunity and immune memory in the newborn lamb . Furthermore, there was no evidence that in utero DNA immunization induced immune tolerance . Our results also indicate that the uptake and expression of the plasmid DNA already occurred within the epithelium of the oral cavity . This correlates with our previous findings that local immune responses were found exclusively in the retropharyngeal lymph nodes draining the oral cavity.

J Biol Chem, 2004 Jun 18, 279(25), 26066 - 73 Epub 2004 Apr 02.
Identification and characterization of the first class of potent bacterial acetyl-CoA carboxylase inhibitors with antibacterial activity; Freiberg C et al.; The multisubunit acetyl-CoA carboxylase, which catalyzes the first committed step in fatty acid biosynthesis, is broadly conserved among bacteria . Its rate-limiting role in formation of fatty acids makes this enzyme an attractive target for the design of novel broad-spectrum antibacterials . However, no potent inhibitors have been discovered so far . This report describes the identification and characterization of highly potent bacterial acetyl-CoA carboxylase inhibitors with antibacterial activity for the first time . We demonstrate that pseudopeptide pyrrolidine dione antibiotics such as moiramide B inhibit the Escherichia coli enzyme at nanomolar concentrations . Moiramide B targets the carboxyltransferase reaction of this enzyme with a competitive inhibition pattern versus malonyl-CoA (K(i) value = 5 nm) . Inhibition at nanomolar concentrations of the pyrrolidine diones is also demonstrated using recombinantly expressed carboxyltransferases from other bacterial species (Staphylococcus aureus, Streptococcus pneumoniae, and Pseudomonas aeruginosa) . We isolated pyrrolidine dione-resistant strains of E . coli, S . aureus, and Bacillus subtilis, which contain mutations within the carboxyltransferase subunits AccA or AccD . We demonstrate that such mutations confer resistance to pyrrolidine diones . Inhibition values (IC(50)) of >100 microm regarding an eukaryotic acetyl-CoA carboxylase from rat liver indicate high selectivity of pyrrolidine diones for the bacterial multisubunit enzyme . The natural product moiramide B and synthetic analogues show broad-spectrum antibacterial activity . The knowledge of the target and the availability of facile assays using carboxyltransferases from different pathogens will enable evaluation of the antibacterial potential of the pyrrolidine diones as a promising antibacterial compound class acting via a novel mode of action.

Appl Environ Microbiol, 2004 Apr, 70(4), 2038 - 43
Stationary-phase quorum-sensing signals affect autoinducer-2 and gene expression in Escherichia coli; Ren D et al.; Quorum sensing via autoinducer-2 (AI-2) has been identified in different strains, including those from Escherichia, Vibrio, Streptococcus, and Bacillus species, and previous studies have suggested the existence of additional quorum-sensing signals working in the stationary phase of Escherichia coli cultures . To investigate the presence and global effect of these possible quorum-sensing signals other than AI-2, DNA microarrays were used to study the effect of stationary-phase signals on the gene expression of early exponential-phase cells of the AI-2-deficient strain E . coli DH5alpha . For statistically significant differential gene expression (P < 0.05), 14 genes were induced by supernatants from a stationary culture and 6 genes were repressed, suggesting the involvement of indole (induction of tnaA and tnaL) and phosphate (repression of phoA, phoB, and phoU) . To study the stability of the signals, the stationary-phase supernatant was autoclaved and was used to study its effect on E . coli gene expression . Three genes were induced by autoclaved stationary-phase supernatant, and 34 genes were repressed . In total, three genes (ompC, ptsA, and btuB) were induced and five genes (nupC, phoB, phoU, argT, and ompF) were repressed by both fresh and autoclaved stationary-phase supernatants . Furthermore, supernatant from E . coli DH5alpha stationary culture was found to repress E . coli K-12 AI-2 concentrations by 4.8-fold +/- 0.4-fold, suggesting that an additional quorum-sensing system in E . coli exists and that gene expression is controlled as a network with different signals working at different growth stages.

Cell, 2004 Apr 2, 117(1), 57 - 68
Conformational antagonism between opposing active sites in a bifunctional RelA/SpoT homolog modulates (p)ppGpp metabolism during the stringent response {corrected}; Hogg T et al.; Enzymes of the Rel/Spo family enable bacteria to survive prolonged periods of nutrient limitation by producing an intracellular signaling alarmone, (p)ppGpp, which triggers the so-called stringent response . Both the synthesis of (p)ppGpp from ATP and GDP(GTP), and its hydrolysis to GDP(GTP) and pyrophosphate, are catalyzed by Rel/Spo proteins . The 2.1 A crystal structure of the bifunctional catalytic fragment of the Rel/Spo homolog from Streptococcus dysgalactiae subsp . equisimilis, Rel(Seq), reveals two conformations of the enzyme corresponding to known reciprocal activity states: (p)ppGpp-hydrolase-OFF/(p)ppGpp-synthetase-ON and hydrolase-ON/synthetase-OFF . The hydrolase and synthetase domains bear remarkable similarities to the catalytic domains of the cyclic phosphodiesterase and nucleotidyltransferase superfamilies, respectively . The active sites, separated by more than 30 A, contain bound nucleotides including an unusual (p)ppGpp derivative, GDP-2':3'-cyclic monophosphate . Reciprocal regulation of the antagonistic catalytic activities, suggested by the structure, is supported by mutagenesis experiments and appears to involve ligand-induced signal transmission between the two active sites.

Laryngoscope, 2004 Apr, 114(4), 675 - 80
Location and timing of initial osteoid deposition in postmeningitic labyrinthitis ossificans determined by multiple fluorescent labels; Tinling SP et al.; OBJECTIVES/HYPOTHESIS: Variable amounts of fibrosis and neo-ossification fill the cochlea following bacterial meningitis . The purpose of the study was to delineate the timing and location of initial ossification following pneumococcal meningitis, as well as subsequent remodeling and resorption, over the 3-month period after infection . STUDY DESIGN: Randomized, double-blind study . METHODS: Fluorochromes are compounds that specifically incorporate into ossifying bone . Sequential addition of different colored fluorochromes during osteoneogenesis define the timing and location of osteoid deposition and mineralization . Mongolian gerbils were infected by intrathecal injection of Streptococcus pneumoniae type 3, and control gerbils received saline . Both groups were injected with calcein on postoperative day 3, followed by xylenol orange, oxytetracycline, and alizarin red on days 7, 14, and 28 respectively . Ten experimental gerbils were killed 24 hours after each label, and an additional group at 84 days after infection . Two groups of 10 control gerbils were killed at 29 and 84 days after treatment . The temporal bones and tibias were harvested, embedded in plastic, and sliced with a diamond saw . Wafers at a thickness of 200 microm were mounted in sequence and examined . RESULTS: Sixteen of 49 experimental animals (33%) were positive for at least one of the fluorescent labels . Fluorescent labeled osteoid was present at all sampling times . Label extended from the endosteal wall into the lumen of the scala tympani between the vestibule and the round window membrane . Discrete sites of fluorescence varied among specimens and were associated with the opening of the cochlear aqueduct, the scala tympani, organ of Corti, and the stria vascularis and spiral ligament in all turns from base to apex . CONCLUSION: The results indicate that osteoid is deposited and begins mineralization by day 3 after infection, at least, and continues, at least, through the first 28 days after infection . There was no apparent resorption of new bone and remodeling by 84 days after infection.

Peptides, 2004 Feb, 25(2), 177 - 83
Lactoferrampin: a novel antimicrobial peptide in the N1-domain of bovine lactoferrin; van der Kraan MI et al.; The antimicrobial activity of bovine lactoferrin is attributed to lactoferricin, situated in the N1-domain . Based on common features of antimicrobial peptides, a second putative antimicrobial domain was identified in the N1-domain of lactoferrin, designated lactoferrampin . This novel peptide exhibited candidacidal activity, which was substantially higher than the activity of lactoferrin . Furthermore, lactoferrampin was active against Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa, but not against the fermenting bacteria Actinomyces naeslundii, Porphyromonas gingivalis, Streptococcus mutans and Streptococcus sanguis . Notably, lactoferrampin is located in the N1-domain in close proximity to lactoferricin, which plays a crucial role in membrane-mediated activities of lactoferrin.

Diagn Microbiol Infect Dis, 2004 Apr, 48(4), 283 - 6
Concentrations of moxifloxacin in serum and synovial fluid, and ex vivo bactericidal activity against arthritis-causing pathogens; Dan M et al.; Three doses of moxifloxacin 400 mg qd were administered orally to 20 candidates for knee arthroscopy (mean age, 71.2 years) . The procedure was scheduled at four different points of time after the last dose: 2, 6, 12, and 24 h . Five patients were studied at each point of time . Drug levels were determined by the bioassay method . Bactericidal activity against four bacterial pathogens (two strains of each) was studied on serum and synovial fluid samples obtained during arthroscopy using the NCCLS guidelines . Mean (+/-S.D.) peak serum and synovial fluid concentrations were 3.46 +/- 0.78 mg/L and 3.42 +/- 0.51 mg/L, respectively . Levels above 1.0 mg/L were detected as long as 24 h . The peak bactericidal titers were (in serum and synovial fluid, respectively) 1:18.3 and 1:32 against Staphylococcus aureus, 1:18.3 and 1:22.6 against Streptococcus pyogenes, 1:45.2 and 1:64.0 against Klebsiella pneumoniae, and 1:2.3 and 1:1.7 against Pseudomonas aeruginosa . Bactericidal titers >1:2 were documented against the first three pathogens up to 24 h after dosing . On the basis of its pharmacokinetic and pharmacodynamic characteristics, moxifloxacin seems to be an excellent candidate for the treatment of joint infections, except those caused by P . aeruginosa.

Scand J Infect Dis, 2004, 36(2), 102 - 5
The effect of dietary fish oil on survival after infection with Klebsiella pneumoniae or Streptococcus pneumoniae; Thors VS et al.; Dietary fish oil is believed to have a beneficial effect in various infections and in autoimmune disorders . This effect may correspond to an altered immune response . In order to discover whether the effect of dietary fish oil is different in various infections, we studied the survival of mice fed fish oil or corn oil supplemented diets and infected in the lungs with either Klebsiella pneumoniae or Streptococcus pneumoniae . 120 NMRI mice were divided into 4 groups, of which 2 groups were fed a fish oil supplemented diet and 2 a corn oil supplemented diet . After 6 weeks the mice were infected in the lungs with Klebsiella pneumoniae (fish oil groups and corn oil groups) or with Streptococcus pneumoniae serotype 3 (both groups) . The survival rate was monitored . The experiment was performed twice . The survival of the mice fed fish oil enriched diet and infected with Klebsiella pneumoniae was significantly better compared with the mice fed corn oil enriched diet (p = 0.0001 and p = 0.0013) . No difference was found between the mice fed corn oil enriched diet or fish oil enriched diet and infected with Streptococcus pneumoniae serotype 3 (p = 0.74 and p = 0.15) . Our results indicate that dietary fish oil has a beneficial effect on survival of mice after experimental pneumoniae when infected with Klebsiella pneumoniae, but not after infection with Streptococcus pneumoniae serotype 3.

Epidemiol Infect, 2004 Apr, 132(2), 375 - 8
Genetic diversity of Streptococcus agalactiae strains colonizing the same pregnant woman; Perez-Ruiz M et al.; Pulsed-field gel electrophoresis (PFGE) of SmaI-DNA digests and serotyping was performed on 15 colonies of Streptococcus agalactiae (GBS) from each of 30 vaginal rectal colonized women . Five distinct GBS serotypes were observed among the 30 specimens (Ia, Ib, II, III and V) . In 29 of the 30 samples, the same serotype was observed among all 15 colonies; in the remaining specimen, the 15 colonies yielded two serotypes (II and V) . The PFGE profiles of all colonies in 27 of the 30 subjects were indistinguishable within each subject . In the remaining women, different DNA profiles were identified among the colonies in each specimen, one of whom carried two different serotypes . Furthermore, strains of the same serotype belonging to different women were genetically heterogeneous.

Epidemiol Infect, 2004 Apr, 132(2), 177 - 84
Invasive Streptococcus pneumoniae isolates from Argentinian children: serotypes, families of pneumococcal surface protein A (PspA) and genetic diversity; Mollerach M et al.; PspA is an antigenically variable virulence factor of Streptococcus pneumoniae that inhibits complement deposition and is a potential candidate for human vaccines . Of 64 published strains 96% are in PspA families 1 and 2; optimal protection is family-specific . Effective development of a PspA-containing vaccine requires more information about the PspA family of strains in parts of the world where the vaccine is most needed . In these studies we observed that of 149 isolates (of 19 capsular types) from Argentina, 54.4% were family 1, 41.6% were family 2 and 4.0% expressed both family 1 and family 2 PspAs . Box typing revealed the Argentinian strains to be from at least 10 clonally related groups.

Epidemiol Infect, 2004 Apr, 132(2), 159 - 66
Prevalence of Streptococcus pneumoniae and Staphylococcus aureus nasopharyngeal colonization in healthy children in the United States; Cheng Immergluck L et al.; This study documents the colonization of Staphylococcus aureus (SA), Streptococcus pneumoniae (SP) and specific resistant forms of these organisms among healthy children and identifies risk factors associated with these pathogens . Prospective point prevalence survey of nasopharyngeal specimens were obtained from 291 healthy children seeking routine well-child care at a university-based ambulatory paediatric clinic in a large urban city in the United States . A total of 291 children less than 5 years were enrolled during a 1-year period . Fifty-four (18.6%) were colonized with SA and 47 (16.2%) were colonized with SP . Among the 54 SA isolates, five (9.2%) were methicillin resistant (MRSA) and among the SP isolates, three (6.4%) were intermediate to penicillin (DRSP) . Eighty per cent of all children enrolled reported no underlying medical condition . Care outside their home was more common among colonized (40.8%, 40/98) than non-colonized children (25.4%, 49/193), P=0.007 . Healthy children from households of four or more people were also more likely to be colonized . The colonization rate of SA and SP among healthy children is consistent with what has been reported in the literature . The prevalence of MRSA and DRSP among healthy children colonized with SA or SP is low in this population of children attending a university-based ambulatory care centre in the United States.

J Microbiol Immunol Infect, 2004 Feb, 37(1), 63 - 6
Streptococcus constellatus causing myocardial abscess complicated by cerebritis; Tsai WC et al.; Streptococcus constellatus infection is a rare cause of myocardial abscess . The complication of cerebritis is also rare . We report a case of S . constellatus bacteremia in a 21-year-old woman who developed fever and watery diarrhea 7 days prior to admission . Computed tomography of the brain showed severe effacement of the cerebral sulci, narrowing of the ventricular system, and severe brain swelling . Echocardiography showed a cystic lesion of about 2 cm(2) over the left atrium . Mannitol and dexamethasone were administered . Hyperventilation was performed . Intravenous penicillin G and ceftazidime were administered but without response . The increased intracranial pressure persisted despite medical treatment . She died 3 days after admission . Culture of cerebrospinal fluid grew S . constellatus and 3 sets of blood cultures grew S . constellatus . This case emphasizes the potential pathogenic role of S . constellatus in myocardial abscess.

J Microbiol Immunol Infect, 2004 Feb, 37(1), 45 - 9
Pediatric lung abscess: a retrospective review of 23 cases; Yen CC et al.; Pulmonary abscess is a rare but critical problem in childhood . We did a retrospective review of 23 children with documented lung abscess who had been admitted and treated at the Taipei Veterans General Hospital over a 20-year period from April 1982 to April 2002 . Among the 23 children, 11 cases were primary lung abscess, and 12 were secondary lung abscess . The pathogens were isolated in 16 patients (69.6%), and blood cultures yielded in only 3 patients (13.0%) . The most common microorganism isolated in this series was Streptococcus pneumoniae . The 2 patients (8.7%) that died in our series had secondary lung abscess . We herein report the presenting symptoms, bacteriology, clinical management, and outcome of these 23 cases.

Pediatrics, 2004 Apr, 113(4), 883 - 6
The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) etiology for tics and obsessive-compulsive symptoms: hypothesis or entity? Practical considerations for the clinician; Kurlan R et al.; Clinicians have been faced with much publicity and contradictory scientific evidence regarding a recently described condition termed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) . It has been proposed that children with PANDAS experience tics, obsessive-compulsive behavior, and perhaps other neuropsychiatric symptoms as an autoimmune response to streptococcal infection . We review current scientific information and conclude that PANDAS remains a yet-unproven hypothesis . Until more definitive scientific proof is forthcoming, there seems to be insufficient evidence to support 1) routine microbiologic or serologic testing for group A streptococcus in children who present with neuropsychiatric symptoms or 2) the clinical use of antibiotic or immune-modifying therapies in such patients . The optimum diagnostic and therapeutic approach awaits the results of additional research studies.

Pediatrics, 2004 Apr, 113(4), 701 - 7
Epidemiology and clinical characteristics of community-acquired pneumonia in hospitalized children; Michelow IC et al.; OBJECTIVES: The precise epidemiology of childhood pneumonia remains poorly defined . Accurate and prompt etiologic diagnosis is limited by inadequate clinical, radiologic, and laboratory diagnostic methods . The objective of this study was to determine as precisely as possible the epidemiology and morbidity of community-acquired pneumonia in hospitalized children . METHODS: Consecutive immunocompetent children hospitalized with radiographically confirmed lower respiratory infections (LRIs) were evaluated prospectively from January 1999 through March 2000 . Positive blood or pleural fluid cultures or pneumolysin-based polymerase chain reaction assays, viral direct fluorescent antibody tests, or viral, mycoplasmal, or chlamydial serologic tests were considered indicative of infection by those organisms . Methods for diagnosis of pneumococcal pneumonia among study subjects were published by us previously . Selected clinical characteristics, indices of inflammation (white blood cell and differential counts and procalcitonin values), and clinical outcome measures (time to defervescence and duration of oxygen supplementation and hospitalization) were compared among groups of children . RESULTS: One hundred fifty-four hospitalized children with LRIs were enrolled . Median age was 33 months (range: 2 months to 17 years) . A pathogen was identified in 79% of children . Typical respiratory bacteria were identified in 60% (of which 73% were Streptococcus pneumoniae), viruses in 45%, Mycoplasma pneumoniae in 14%, Chlamydia pneumoniae in 9%, and mixed bacterial/viral infections in 23% . Preschool-aged children had as many episodes of atypical bacterial LRIs as older children . Children with typical bacterial or mixed bacterial/viral infections had the greatest inflammation and disease severity . Multivariate logistic-regression analyses revealed that high temperature (> or = 38.4 degrees C) within 72 hours after admission (odds ratio: 2.2; 95% confidence interval: 1.4-3.5) and the presence of pleural effusion (odds ratio: 6.6; 95% confidence interval: 2.1-21.2) were significantly associated with bacterial pneumonia . CONCLUSIONS: This study used an expanded diagnostic armamentarium to define the broad spectrum of pathogens that cause pneumonia in hospitalized children . The data confirm the importance of S pneumoniae and the frequent occurrence of bacterial and viral coinfections in children with pneumonia . These findings will facilitate age-appropriate antibiotic selection and future evaluation of the clinical effectiveness of the pneumococcal conjugate vaccine as well as other candidate vaccines.

J Biol Chem, 2004 May 21, 279(21), 22198 - 203 Epub 2004 Apr 01.
Peptide mapping of a novel discontinuous epitope of the major surface adhesin from Streptococcus mutans; van Dolleweerd CJ et al.; Guy's 13 is a mouse monoclonal antibody that specifically recognizes the major cell-surface adhesion protein SA I/II of Streptococcus mutans, one of the major causative agents of dental caries . Passive immunization with Guy's 13 prevents bacterial colonization in humans . To help elucidate the mechanism of prevention of colonization conferred by this antibody, the SA I/II epitope recognized by Guy's 13 was investigated . It was previously established that the epitope is conformational, being assembled from two non-contiguous regions of SA I/II . In the current study, using recombinant fragments of SA I/II and, ultimately, synthetic peptides, the discontinuous epitope was localized to residues 170-218 and 956-969 . This work describes the mapping of a novel discontinuous epitope that requires an interaction between each determinant in order for epitope assembly and recognition by antibody to take place . Guy's 13 binds to the assembled epitope but not to these individual epitope fragments . The assembled epitope results from the interaction between the individual antigenic determinants and can be formed by mixing together determinants present on separate polypeptide chains . The data are consistent with one of the epitope fragments adopting a polyproline II-like helical conformation.

J Bacteriol, 2004 Apr, 186(8), 2511 - 4
Control of expression of the arginine deiminase operon of Streptococcus gordonii by CcpA and Flp; Dong Y et al.; In Streptococcus gordonii DL1, inactivation of the ccpA gene and a gene encoding an Fnr-like protein (Flp) demonstrated that CcpA was essential for carbohydrate catabolite repression and that Flp was required for optimal expression and anaerobic induction of the arginine deiminase system.

J Bacteriol, 2004 Apr, 186(8), 2346 - 54
Characterization of Streptococcus pneumoniae TrmD, a tRNA methyltransferase essential for growth; O'Dwyer K et al.; Down-regulation of expression of trmD, encoding the enzyme tRNA (guanosine-1)-methyltransferase, has shown that this gene is essential for growth of Streptococcus pneumoniae . The S . pneumoniae trmD gene has been isolated and expressed in Escherichia coli by using a His-tagged T7 expression vector . Recombinant protein has been purified, and its catalytic and physical properties have been characterized . The native enzyme displays a molecular mass of approximately 65,000 Da, suggesting that streptococcal TrmD is a dimer of two identical subunits . In fact, this characteristic can be extended to several other TrmD orthologs, including E . coli TrmD . Kinetic studies show that the streptococcal enzyme utilizes a sequential mechanism . Binding of tRNA by gel mobility shift assays gives a dissociation constant of 22 nM for one of its substrates, tRNA(Leu)(CAG) . Other heterologous nonsubstrate tRNA species, like, tRNA (Thr)(GGT), tRNA(Phe), and tRNA (Ala)(TGC), bind the enzyme with similar affinities, suggesting that tRNA specificity is achieved via a postbinding event(s).

Infection, 2004 Apr, 32(2), 59 - 64
Bloodstream infection-associated sepsis and septic shock in critically ill adults: a population-based study; Laupland KB et al.; BACKGROUND: Few studies have investigated the epidemiology of sepsis and septic shock in a large population and none have been from Canada . The objective of this study was to define the epidemiology of bloodstream infection (BSI)-associated sepsis and septic shock among all critically ill patients in a large, fully integrated health region in Canada . PATIENTS AND METHODS: All critically ill adults admitted to multidisciplinary intensive care units (ICU) in the Calgary Health Region during May 1, 1999 to April 30, 2000 were included . Clinical, microbiologic and outcome information was obtained from regional databases . RESULTS: We surveyed 1981 patients having at least one ICU admission . Systemic inflammatory response syndrome (SIRS) was diagnosed in 92%, BSI-associated sepsis (BSI with SIRS) in 6% and BSI-associated septic shock (BSI with SIRS and hypotension) in 3%; respective hospital mortality rates were 36%, 40% and 49% . The most common BSI etiologies were Staphylococcus aureus, Escherichia coli and Streptococcus species; only one isolate (1%) was highly antibiotic resistant . Independent risk factors for death among patients with SIRS included age (>or= 65), hypothermia (< 35 degrees C), and higher APACHE II and TISS scores . A surgical diagnosis was associated with decreased mortality risk . Neither a positive blood culture nor hypotension at presentation independently predicted death . CONCLUSION: Knowledge of the epidemiology of these syndromes is important for assessing the burden of disease and providing background information for investigating new therapies.

Curr Microbiol, 2004 Mar, 48(3), 230 - 6
Identification, molecular cloning, and sequence analysis of a deoxyribose aldolase in Streptococcus mutans GS-5; Han TK et al.; Bacterial fitness in the environment, where nutrients are limited and competition is intense, plays a central role in survival and virulence of the organisms . Deoxyribose aldolase, found in several species of bacteria, is known to be involved in the catabolism of deoxynucleosides arising from dead cells, thereby giving a selective advantage to the microorganisms with a capability to consume DNA as an alternative carbon and energy source . A gene encoding a deoxyribose aldolase gene ( deoC) was identified in the cariogenic Streptococcus mutans strain GS-5 by comparative sequence analysis and gene cloning . The gene encodes a protein of 220 amino acids, having a predicted molecular weight of 23.3 kDa with a p I of 5.44 . The gene was cloned into the expression vector pFLAG-1, and the biological function of the gene product was analyzed by a complementation assay with a deoC(-) Escherichia coli mutant SPhi063 . Transformation of the E . coli SPhi063 with the plasmid construct allowed this organism to grow on glucose minimal medium supplemented with 2 mM deoxyadenosine or deoxythymidine . These results showed activity of deoxyribose aldolase, confirming the identity of the gene . Utilization of exogenous deoxynucleotides as a carbon and energy source may confer a survival and growth advantage to S . mutans over other bacteria in dental plaque, suggesting that deoxyribose aldolase may be a contributing factor to virulence.

Reproduction, 2004 Jan, 127(1), 57 - 66
Alteration in uterine contractility in mares with experimentally induced placentitis; McGlothlin JA et al.; An experimental model of ascending placentitis was developed in the mare to characterize the uterine myoelectrical pattern in late gestation and determine how ascending placentitis altered this pattern . In experiment 1, myometrial electrical activity was analyzed during the early morning, late morning and evening hours in four mares in the last 15 days of gestation to identify patterns of activity . In experiment 2, nine mares received intra-cervical inoculations of Streptococcus equi subspecies zooepidemicus . Myoelectrical activity in the early morning and evening hours in these mares was compared with four control mares . In experiment 1, the number of spike burst clusters >30 s was greater in the evening than in the late morning hours (P < 0.04) . Spike burst activity (number x duration) of mares in experiment 1 was similar during day and night recordings until the last 6 days of gestation when it gradually increased each evening until parturition (P < 0.05) . In experiment 2, control mares experienced a gradual increase in the number of small spike burst clusters in the last 6 days (P = 0.008) and an increase in large and small spike burst clusters in the evening hours in the last 4 days of gestation (P = 0.03) . Mares with experimentally induced placentitis never exhibited a rise in spike burst clusters but had an increase in the mean duration and activity index of large spike burst clusters in the 4 days before parturition (P < 0.04) . In conclusion, control mares had a progressive, reversible rise in myoelectrical activity at night in the week preceding parturition . This was not observed in mares with experimentally induced placentitis . They exhibited an increase in the intensity and duration of large spike burst clusters possibly in response to local inflammation.

Indian J Med Res, 2004 Feb, 119(2), 75 - 8
Detection of pneumolysin in cerebrospinal fluid for rapid diagnosis of Pneumococcal meningitis; Kanungo R et al.; BACKGROUND & OBJECTIVES: Pneumolysin, a toxin produced by Streptococcus pneumoniae is associated with virulence and is found in all invasive isolates . Its role as a diagnostic tool has recently been exploited . Most of the methods used are based on molecular techniques and are not cost-effective . The present study was undertaken to evaluate a simple, rapid and cost-effective method to detect pneumolysin in CSF as a diagnostic test for pneumococcal meningitis . METHODS: A total of 75 CSF samples from children with presumptive diagnosis of acute pyogenic meningitis or encephalitis were subjected to Gram stain, culture and pneumolysin detection by Cowan 1 staphylococcal protein A co-agglutination technique . RESULTS: Pneumolysin was detected in 26(78.8%) of 33 culture proven CSF samples and 4(9.5%) of 42 culture negative samples . Antigen detection by Co-A had a specificity of 90 per cent and a sensitivity of 79 per cent when compared with culture . Compared to Gram stain, pneumolysin Co-A had a specificity and sensitivity of 91.0 and 92.0 per cent respectively . INTERPRETATION & CONCLUSION: Detection of pneumolysin was found to be a simple, low cost antigen detection assay for rapid diagnosis of pneumococcal meningitis, for routine use in the developing countries.

J Endod, 2004 Mar, 30(3), 177 - 9
Effect of a separated instrument on bacterial penetration of obturated root canals; Saunders JL et al.; The aim of this study was to determine the effect a separated instrument has on the time required for bacterial penetration of obturated root canals . Twenty-six extracted human mandibular premolars with single canals were used in the study . Group 1 consisted of teeth that contained a separated size 40 Profile rotary file and were obturated with gutta-percha and zinc oxide eugenol sealer to the level of the separated file . Group 2 consisted of teeth that were similarly obturated, but without a separated file . The negative control canals were obturated and had the entire root surface sealed with nail polish . The positive controls were obturated without sealer . Streptococcus sanguis was placed in the access chamber daily, and penetration was determined when turbidity was noted in the culture broth . The results showed no significant difference between the two experimental groups.

J Endod, 2004 Mar, 30(3), 154 - 8
In vitro microbial leakage of endodontically treated teeth using new and standard obturation techniques; Shipper G et al.; Coronal microbial leakage is an important cause of apical periodontitis and thus should be prevented if possible . The purpose of this study was to compare microbial leakage of new and standard obturation techniques over a 30-day period . A split chamber microbial leakage model was used in which Streptococcus mutans placed in the upper chamber could reach the lower chamber only through the obturated canal . Leakage was assessed every day for 30 days . One hundred forty single-rooted human teeth were used in this study, equally split between lateral, vertical, and Obtura II condensation; SimpliFill with Obtura II condensation; FibreFill; and a combination of FibreFill and SimpliFill . Cochran-Mantel-Haenszel row mean score statistics showed a high statistical significance when all groups were compared (p < 0.0001) . Microbial leakage occurred more quickly in lateral and vertical condensation techniques compared with SimpliFill and FibreFill techniques . A combination of an apical plug of gutta-percha with SimpliFill and a FibreFill coronal seal was the best obturation technique used (SimpliFill-FibreFill group).

Ned Tijdschr Geneeskd . 2004 Mar 13;148(11):524.
{Diagnostic image (180) . A woman with painful erythema after breast -conserving surgery . Erysipelas caused by group B Streptococcus agalactiae}; van den Wildenberg FJ et al.; A 60-year-old woman presented a year after breast-conserving surgery with severe erysipelas caused by a group-B Streptococcus agalactiae . She recovered after treatment with intravenous penicillin.

J Nutr, 2004 Apr, 134(4), 989S - 95S
Bioactive properties of milk proteins with particular focus on anticariogenesis; Aimutis WR; Beyond nutrition, there is an increasing amount of data and information to demonstrate a bioactive role for dairy components in adults including a role in prevention of dental caries . Specifically, the casein fraction and hydrolysates thereof have been the focus of researchers investigating cariogenicity prevention . Tooth enamel is a polymeric substance consisting of crystalline calcium phosphate embedded in a protein matrix . Dental caries develop by acidic demineralization (calcium and phosphorus solubilization) of tooth enamel . Demineralization occurs directly (acidic food consumption) or indirectly (by fermentation products of dental plaque odontopathogenic bacteria growing on residual food particles between teeth or adhering to the plaque) . Research efforts with milk derived bioactive peptides have focused on inhibition of cariogenic, plaque-forming bacteria, inhibition of tooth enamel demineralization, and subsequent enamel remineralization . Caseinophosphopeptides (CPP) and glycomacropeptide (GMP) have been patented for use in common personal hygiene products to prevent dental caries . Research has shown CPP and GMP to be growth inhibitory to the cariogenic bacteria Streptococcus mutans and other species . Additionally, CPP forms nanoclusters with amorphous calcium phosphate (AMP) at the tooth surface to provide a reservoir of calcium and phosphate ions to maintain a state of super saturation with respect to tooth enamel . This would buffer plaque pH, and also provide ions for tooth enamel remineralization . Glycosidic structures attached to GMP are important to numerous bioactive properties of the peptide including anticariogenicity . Like CPP, GMP has shown inhibitory activity to enamel demineralization and promotes tooth enamel remineralization.

Rev Med Interne, 2004 Apr, 25(4), 303 - 5
{A case of association of atypical localisations of Streptococcus pneumoniae}; Quintard H et al.; Streptococcus pneumoniae can be responsible for spinal, joints, pulmonary or infrequently cutaneous septic localisations . The association between different septic localisation is extremely rare with this microorganism . We describe the first case of concomitant spinal, joints and cutaneous septic localisations in a critically ill patient with S . pneumoniae septicaemia . This observation illustrates that heterogeneity of clinical features depends on the pathogen characteristic and its interaction with the host.

Mol Microbiol, 2004 Apr, 52(1), 189 - 203
Genes in the accessory sec locus of Streptococcus gordonii have three functionally distinct effects on the expression of the platelet-binding protein GspB; Takamatsu D et al.; Platelet binding by Streptococcus gordonii strain M99 is strongly correlated with the expression of the large surface glycoprotein GspB . A 14 kb chromosomal region downstream of gspB was previously shown to be required for the expression of this protein . The region encodes SecA2 and SecY2, which are components of an accessory secretion system dedicated specifically to the export of GspB . The region also includes three genes (gly, nss and gtf) that encode proteins likely to function in carbohydrate metabolism, and four genes (orf1-4) that encode proteins of unknown function . In this report, we have investigated the role of these genes in GspB expression . We found that disruption of orf1, orf2 or orf3 resulted in a loss of GspB export and the intracellular accumulation of GspB . As they are apparently essential components of the accessory secretion system, these genes were renamed asp1-3 (for accessory secretory protein) . In gtf and orf4 mutants, gspB was transcribed, but no GspB was detected . These results suggest that Gtf and Orf4 are required for the translation or for the stability of GspB . In contrast, gly and nss mutants were able to express and export GspB . However, disruption of these genes appeared to affect the carbohydrate composition of this glycoprotein . As asp1-3, gtf and orf4, but not gly and nss, are conserved in the accessory sec loci of several staphylococcal and streptococcal species, these genes may also have crucial roles in the expression and export of GspB homologues in the other Gram-positive bacteria.

Scand J Immunol, 2004 Apr, 59(4), 345 - 55
Interplay between superantigens and immunoreceptors; Petersson K et al.; Superantigens (SAGs) cause a massive T-cell proliferation by simultaneously binding to major histocompatibility complex (MHC) class II on antigen-presenting cells and T-cell receptors (TCRs) on T cells . These T-cell mitogens can cause disease in host, such as food poisoning or toxic shock . The best characterized groups of SAGs are the bacterial SAGs secreted by Staphylococcus aureus and Streptococcus pyogenes . Despite a common overall three-dimensional fold of these SAGs, they have been shown to bind to MHC class II in different ways . Recently, it has also been shown that SAGs have individual preferences in their binding to the TCRs . They can interact with various regions of the variable beta-chain of TCRs and at least one SAG seems to bind to the alpha-chain of TCRs . In this review, different subclasses of SAGs are classified based upon their binding mode to MHC class II, and models of trimolecular complexes of MHC-SAG-TCR molecules are described in order to reveal and understand the complexity of SAG-mediated T-cell activation.

Antimicrob Agents Chemother, 2004 Apr, 48(4), 1419 - 21
Eradication of Streptococcus pneumoniae in the nasopharyngeal flora of children with acute otitis media after amoxicillin-clavulanate therapy; Brook I et al.; Nasopharyngeal cultures were obtained from 60 children with acute otitis media before and after treatment with either 45 or 90 mg of amoxicillin (given as amoxicillin-clavulanate) per kg of body weight per day for 10 days . The number of Streptococcus pneumoniae isolates in the 45-mg/kg group was reduced from 12 to 6 and was reduced from 14 to 1 (P = 0.0261) in the 90-mg/kg group.

Antimicrob Agents Chemother, 2004 Apr, 48(4), 1369 - 73
Clonal relatedness of erythromycin-resistant Streptococcus pyogenes isolates in Germany; Reinert RR et al.; In a nationwide study in Germany, a total of 381 Streptococcus pyogenes were collected . Erythromycin A-resistant strains were characterized for the underlying resistance genotype, showing 55.6% had the efflux type mef(A), 31.5% had erm(A), and 13.0% had erm(B) . A total of 23 different multilocus sequence types were observed.

Antimicrob Agents Chemother, 2004 Apr, 48(4), 1215 - 21
Pharmacodynamics of moxifloxacin and levofloxacin at simulated epithelial lining fluid drug concentrations against Streptococcus pneumoniae; Florea NR et al.; Recent clinical failures associated with levofloxacin treatment for Streptococcus pneumoniae infections and growing evidence of frequent mutations in the isolate population have led to increased concerns regarding fluoroquinolone resistance . Our objective was to characterize the efficacies of levofloxacin and moxifloxacin against various genotypes of S . pneumoniae after simulated bronchopulmonary exposures . An in vitro model was used to simulate a levofloxacin concentration of 500 mg and a moxifloxacin concentration of 400 mg, which were previously determined to be the concentrations in the epithelial lining fluid of older adults receiving once-daily dosing . The effects of the drugs were tested against six S . pneumoniae containing various mutations . Bacterial density and resistance were quantitatively assessed over 48 h . The S . pneumoniae isolate with no mutation displayed a 4-log reduction in CFU after treatment with both agents and did not develop resistance . Isolates containing the parC or parE mutation or both mutations regrew and developed resistance when they were exposed to levofloxacin, despite an unbound area under the concentration-time curve (AUC):MIC ratio of approximately 100 . When the isolate containing the parC and gyrA mutations was exposed to levofloxacin, there was a half-log reduction in the number of CFU compared to that for the control, but the isolate subsequently regrew . Likewise, levofloxacin did not kill the isolate containing the parC, gyrA, and parE mutations . Moxifloxacin sustained the killing of all bacterial isolates tested without the development of resistance . Levofloxacin did not sustain bacterial killing and did not prevent the emergence of further resistance in mutants with the parC or parE mutation or both mutations, even though an unbound AUC:MIC ratio for exposure well above the breakpoint of 30 to 40 established in the literature for S . pneumoniae was maintained . Moxifloxacin was effective against all isolates tested, despite the presence of isolates with two- and three-step mutations, for which the MICs were increased.

Biomaterials, 2004 Aug, 25(18), 4457 - 63
Evaluation of bacterial adhesion of Streptococcus mutans on dental restorative materials; Montanaro L et al.; Bacterial adhesion to the surface of composite resins and other dental restorative materials is an important parameter in the aetiology of secondary caries formation . The aim of the present study was to investigate the adhesion of a Streptococcus mutans strain (ATCC 25175) on the surface of different restorative materials . The test materials examined included three flowable composites (Filtek Flow, Tetric Flow, and Arabesk Flow), three microhybrid composites (Clearfil APX, Solitaire 2, and Z250), two glass-ionomers (Fuji IX, Fuji IX fast), a compomer (F2000), an ormocer (Admira), and a control reference material (tissue culture grade, surface treated polystyrene) . The adhesion tests were carried out in 24-well plates . Quantitative turbidimetric measurements were finally performed in order to indirectly evaluate the amount of bacteria retained on the material surface after in vitro exposure to the bacteria suspension . Under these conditions, with the exception of the Admira ormocer and the Fuji IX fast glass ionomer, which were found to be more adhesive, all the other material surfaces showed a similar susceptibility to bacterial adhesion, exhibiting values not significantly different than the reference polystyrene control . Furthermore, the release of fluoride from some of the test surfaces did not appear capable to reduce early bacterial adhesion.

Syst Appl Microbiol, 2004 Mar, 27(2), 146 - 50
Streptococcus devriesei sp . nov., from equine teeth; Collins MD et al.; Phenotypic and phylogenetic studies were performed on four unidentified Gram-positive staining, catalase-negative, alpha-hemolytic Streptococcus-like organisms recovered from the teeth of horses . SDS PAGE analysis of whole-cell proteins and comparative 16S rRNA gene sequencing demonstrated the four strains were highly related to each other but that they did not correspond to any recognised species of the genus Streptococcus . Phylogenetic analysis based on 16S rRNA gene sequences showed the unidentified organisms form a hitherto unknown sub-line within the Streptococcus genus, displaying a close affinity with Streptococcus mutans, Streptococcus ferus and related organisms . Sequence divergence values of > 5% with these and other reference streptococcal species however demonstrated the organisms from equine sources represent a novel species . Based on the phenotypic distinctiveness of the new bacterium and molecular chemical and molecular genetic evidence, it is proposed that the unknown species be classified as Streptococcus devriesei sp . nov . The type strain of Streptococcus devriesei is CCUG 47155T (= CIP 107809T).

J Dent Res, 2004 Apr, 83(4), 354 - 8
Therapeutic vaccine against Streptococcus sobrinus-induced caries; Dinis M et al.; Streptococcus sobrinus produces a virulence-associated immunomodulatory protein (VIP) which suppresses the host-specific immune response and induces the early production of IL-10 . In this study, we evaluated the effects of therapeutic immunization with this VIP on the incidence of caries in S . sobrinus-infected rats . Groups of Wistar rats were orally infected with S . sobrinus and fed with sucrose-sweetened drinking water ad libitum . Five days later, rats were immunized intranasally with active or heat-inactivated VIP plus alum as adjuvant or PBS plus adjuvant (sham-immunized) . After 3 wks, all rats were re-immunized as above . Evaluation of dental caries showed that VIP-immunized animals had significantly fewer enamel sulcal and proximal caries lesions than did the sham-immunized animals (p < 0.001) . The protective effects following therapeutic VIP immunization were attributed to the induced salivary immunoglobulin A specific to the VIP . These results offer a promising and safe strategy for the development of a vaccine against dental caries.

J Biol Chem, 2004 May 28, 279(22), 23590 - 6 Epub 2004 Mar 24.
Characterization of human UDP-glucose dehydrogenase . CYS-276 is required for the second of two successive oxidations; Sommer BJ et al.; UDP-glucose dehydrogenase (UGDH) catalyzes two oxidations of UDP-glucose to yield UDP-glucuronic acid . Pathological overproduction of extracellular matrix components may be linked to the availability of UDP-glucuronic acid; therefore UGDH is an intriguing therapeutic target . Specific inhibition of human UGDH requires detailed knowledge of its catalytic mechanism, which has not been characterized . In this report, we have cloned, expressed, and affinity-purified the human enzyme and determined its steady state kinetic parameters . The human enzyme is active as a hexamer with values for Km and Vmax that agree well with those reported for a bovine homolog . We used crystal coordinates for Streptococcus pyogenes UGDH in complex with NAD+ cofactor and UDP-glucose substrate to generate a model of the enzyme active site . Based on this model, we selected Cys-276 and Lys-279 as likely catalytic residues and converted them to serine and alanine, respectively . Enzymatic activity of C276S and K279A point mutants was not measurable under normal assay conditions . Rate constants measured over several hours demonstrated that K279A continued to turn over, although 250-fold more slowly than wild type enzyme . C276S, however, performed only a single round of oxidation, indicating that it is essential for the second oxidation . This result is consistent with the postulated role of Cys-276 as a catalytic residue and supports its position in the reaction mechanism for the human enzyme . Lys-279 is likely to have a role in positioning active site residues and in maintaining the hexameric quaternary structure.

FEMS Microbiol Lett, 2004 Apr 1, 233(1), 147 - 52
Virulence of Streptococcus pneumoniae may be determined independently of capsular polysaccharide; Mizrachi Nebenzahl Y et al.; Mice were inoculated intranasally with Streptococcus pneumoniae isolates of serotype 14 with different genetic backgrounds (14R, 14DW) and a capsular switch of 14R, strain 9VR (serotype 9V) . Inoculation of the mice with 14R and 9VR resulted in 60% mortality . All the mice survived 14DW inoculation . No differences in lungs' bacterial loads were found 3 h following inoculation . Bacterial clearance of 5 logs was observed 48 h after inoculation with 14DW versus within 1 log 48 h after inoculation with 14R and 9VR . No significant differences in bacterial size or the capsular amount could be found between 14R and 14DW . We conclude that factor(s) in addition to the capsule, contribute to disease outcome.

Microb Pathog, 2004 May, 36(5), 273 - 85
Histopathologic changes in kidney and liver correlate with streptococcal pyrogenic exotoxin B production in the mouse model of group A streptococcal infection; Kuo CF et al.; Previous studies show that isogenic mutants deficient in streptococcal pyrogenic exotoxin B (SPE B) cause less mortality and skin tissue damage than wild-type strains of Streptococcus pyogenes when inoculated into mice via an air pouch . In this study, the growth and dissemination of bacteria, pathologic changes in various organs, and their correlation with SPE B production were examined . Bacterial numbers in the air pouch from wild-type strain NZ131-infected mice increased at 48 h, while those from speB mutant SW510-infected mice continuously reduced . Mice infected with NZ131 developed bacteremia and greater dissemination in the kidney, liver, and spleen; those infected with SW510 showed either no or slight bacteremia and dissemination . Co-inoculation of SW510 with recombinant SPE B showed a higher bacterial count in the air pouch, bacteremia, and organ dissemination compared to co-inoculation with a C192S mutant lacking protease activity . The histopathologic changes examined showed lesions in kidney and liver in the NZ131-infected but not in SW510-infected mice . The elevation in sera of BUN, AST, and ALT correlated positively with renal and liver impairment . Taken together, SPE B produced during S . pyogenes infection plays a pathogenic role . A direct effect of SPE B on vessel permeability change was also demonstrated.

Infect Immun, 2004 Apr, 72(4), 2434 - 7
Protein serine/threonine kinase StkP positively controls virulence and competence in Streptococcus pneumoniae; Echenique J et al.; In the Streptococcus pneumoniae genome, stkP, encoding a membrane-associated serine/threonine kinase, is not redundant (L . Novakova, S . Romao, J . Echenique, P . Branny, and M.-C . Trombe, unpublished results) . The data presented here demonstrate that StkP belongs to the signaling network involved in competence triggering in vitro and lung infection and bloodstream invasion in vivo . In competence, functional StkP is required for activation of comCDE upstream of the autoregulated ring orchestrated by the competence-stimulating peptide . This is the first description of positive regulation of comCDE transcription in balance with its repression by CiaRH.

Infect Immun, 2004 Apr, 72(4), 2416 - 9
Glyceraldehyde-3-phosphate dehydrogenase of Streptococcus pneumoniae is a surface-displayed plasminogen-binding protein; Bergmann S et al.; The recruitment of plasminogen endows the bacterial cell surface of Streptococcus pneumoniae with proteolytic activity . In this study we demonstrate specific plasmin- and plasminogen-binding activity for the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which is located in the cytoplasm as well as on the surface of pneumococci . GAPDH exhibits a high affinity for plasmin and a significantly lower affinity for plasminogen.

FEMS Immunol Med Microbiol, 2004 Apr 9, 40(3), 249 - 56
Immune response to superoxide dismutase in group A streptococcal infection; McMillan DJ et al.; Extracellular localisation of manganese-dependent superoxide dismutase (SodA) by group A streptococcus (GAS) may have a role in protection of this pathogenic bacterium from exogenously produced reactive oxygen species . In this study we show that SodA is found both in surface protein extracts and in culture supernatants of GAS . To investigate whether SodA is a possible vaccine candidate outbred Quackenbush mice were subcutaneously vaccinated with recombinant SodA . Strong antibody responses which were moderately opsonic were elicited . These antibodies were unable to protect mice from intraperitoneal challenge with M1 GAS . We also show that SodA and p145 (a conserved peptide from the M-protein) antibodies are present at significantly higher levels amongst patients with rheumatic heart disease than in control subjects from the same endemic region . The higher SodA antibody levels in patients may be indicative of a role for this protein in pathogenesis of rheumatic heart disease but are more likely to be a marker of recent or recurrent streptococcal infection.

Clin Ther, 2004 Feb, 26(2), 224 - 31
Efficacy and tolerability of moxifloxacin in the treatment of acute bacterial sinusitis caused by penicillin-resistant Streptococcus pneumoniae: a pooled analysis; Johnson P et al.; BACKGROUND: Penicillin-resistant Streptococcus pneumoniae (PRSP) has become a relatively common pathogen in upper and lower respiratory tract infections, including acute bacterial sinusitis (ABS) . OBJECTIVE: The goal of this analysis was to assess the efficacy and tolerability of moxifloxacin in the treatment of ABS caused by penicillin-sensitive S pneumoniae (PSSP) and PRSP METHODS: Two prospective, multicenter, open-label, noncomparative US trials of moxifloxacin were included in this pooled analysis . All patients received oral moxifloxacin 400 mg once daily for 7 to 10 days . Minimum inhibitory concentrations (MICs) of moxifloxacin and penicillin were determined using the E-test and standard broth-microdilution methods . The primary end point was clinical success at the test-of-cure visit (21-37 days after completion of therapy) in patients with a positive pretherapy sinus culture . Data are presented for patients with ABS caused by both PSSP and PRSP RESULTS: Of 806 patients enrolled in the 2 studies, 146 had microbiologically confirmed bacterial infection . Sixty-nine patients had ABS caused by S pneumoniae, including 15 confirmed cases of PRSP infection . The majority of the 69 clinically evaluable patients were white (n = 63) and female (n = 46), and the mean age of this population was 43 years . Investigators categorized the episode of ABS as severe in 26 (37.7%) of clinically evaluable patients and of moderate severity in the remainder (62.3% {43}); however, most patients (78.3% {54/69}) reported >/=1 severe symptom . The episode of ABS was classified as severe in 8 (53.3%) of the 15 patients with PRSP infection . Clinical and bacteriologic success at the test-of-cure visit was achieved in 93.3% (14/15) of patients with PRSP infection, compared with 88.4% (61/69) of all patients infected with S pneumoniae regardless of penicillin susceptibility . Moxifloxacin MICs against the 15 PRSP strains ranged from 0.06 to 0.25 microg/mL . Data from 805 patients were available for tolerability analysis . The most commonly occurring adverse events were nausea, headache, and diarrhea . Generally, adverse events were mild to moderate . None of the 6 serious adverse events reported were considered related to moxifloxacin therapy . CONCLUSION: In this small cohort of patients, moxifloxacin provided clinical and bacteriologic cures in the majority of patients with ABS caused by PRSP, including those with severe sinusitis.

J Health Popul Nutr, 2003 Dec, 21(4), 316 - 24
Factors associated with carriage of penicillin-resistant Streptococcus pneumoniae among Vietnamese children: a rural-urban divide; Quagliarello AB et al.; This study examined the relationship between antimicrobial resistance in Streptococcus pneumoniae and patterns of antimicrobial usage and over-the-counter dispensing by pharmacies in urban and rural districts of Vietnam . The antimicrobial susceptibility of S . pneumoniae carried by healthy urban and rural school children was determined . Questionnaires were distributed to parents to describe their healthcare-seeking behaviour . Mock parents presented standardized cases of mild respiratory infection and acute watery diarrhoea to pharmacies in the district surrounding each school . Penicillin resistance was significantly more common in S . pneumoniae carried by urban children compared to rural children as was recent antibiotic usage . Both urban and rural pharmacies showed high rates of dispensing inadequate antimicrobial regimens . The high level of antimicrobial resistance in S . pneumoniae may be related to greater antimicrobial usage . This may result from the much easier access to healthcare providers in urban areas and may suggest that relying solely on education without limiting access to outlets may have only limited impact . The results suggest a greater understanding of the subtleties of healthcare-seeking behaviour, and access to healthcare is needed to help refine and guide rationale suggestions to reduce the continued spread of drug resistance.

Clin Infect Dis, 2004 Apr 1, 38(7), 994 - 1000 Epub 2004 Mar 11.
Daptomycin: another novel agent for treating infections due to drug-resistant gram-positive pathogens; Carpenter CF et al.; Daptomycin is a novel cyclic lipopeptide antibiotic that provides rapid bactericidal activity against gram-positive pathogens in vitro, including methicillin-susceptible Staphylococcus aureus, methicillin-resistant S . aureus, vancomycin-resistant S . aureus, penicillin-resistant Streptococcus pneumoniae, and ampicillin- and vancomycin-resistant enterococci . The United States Food and Drug Administration recently approved daptomycin for treatment of complicated skin and skin-structure infections . Its efficacy in the treatment of more-serious infections (e.g., staphylococcal bacteremia) is under investigation . As an intravenous agent that is administered once per day, it offers a convenient regimen for therapy that is continued after discharge, with a side effect profile that appears minimal and manageable . Spontaneous acquisition of resistance in vitro is rare, and hopefully this characteristic will extrapolate into the clinical setting . The rapid bactericidal activity, low potential for resistance, and promising safety profile associated with this agent will make it a useful addition to our growing armamentarium of antibiotics active against gram-positive pathogens.

Microbiol Immunol, 2004, 48(3), 155 - 62
Molecular characterization of dextranase from Streptococcus rattus; Igarashi T et al.; The complete nucleotide sequence of the dextranase gene of Streptococcus rattus ATCC19645 was determined . An open reading frame of the dextranase gene was 2,760 bp long and encoded a dextranase protein consisting of 920 amino acids with a molecular weight of 100,163 Da and an isoelectric point of 4.67 . The S . rattus dextranase purified from recombinant Escherichia coli cells showed dextran-hydrolyzing activity with optimal pH (5.0) and temperature (40 C) similar to those of dextranases from Streptococcus mutans and Streptococcus sobrinus . The deduced amino acid sequence of the S . rattus dextranase revealed that the dextranase molecule consists of two variable regions and a conserved region . The variable regions contained an N-terminal signal peptide and a C-terminal cell wall sorting signal; the conserved region contained two functional domains, catalytic and dextran-binding sites . This structural feature of the S . rattus dextranase is quite similar to that of other cariogenic species such as S . mutans, S . sobrinus, and Streptococcus downei.

Antonie Van Leeuwenhoek, 2004 May, 85(4), 305 - 15
Putative lipoproteins of Streptococcus agalactiae identified by bioinformatic genome analysis; Sutcliffe IC et al.; Streptococcus agalactiae is a significant pathogen causing invasive disease in neonates and thus an understanding of the molecular basis of the pathogenicity of this organism is of importance . N-terminal lipidation is a major mechanism by which bacteria can tether proteins to membranes . Lipidation is directed by the presence of a cysteine-containing 'lipobox' within specific signal peptides and this feature has greatly facilitated the bioinformatic identification of putative lipoproteins . We have designed previously a taxon-specific pattern (G+LPP) for the identification of Gram-positive bacterial lipoproteins, based on the signal peptides of experimentally verified lipoproteins (Sutcliffe I.C . and Harrington D.J . Microbiology 148: 2065-2077) . Patterns searches with this pattern and other bioinformatic methods have been used to identify putative lipoproteins in the recently published genomes of S . agalactiae strains 2603/V and NEM316 . A core of 39 common putative lipoproteins was identified, along with 5 putative lipoproteins unique to strain 2603/V and 2 putative lipoproteins unique to strain NEM316 . Thus putative lipoproteins represent ca . 2% of the S . agalactiae proteome . As in other Gram-positive bacteria, the largest functional category of S . agalactiae lipoproteins is that predicted to comprise of substrate binding proteins of ABC transport systems . Other roles include lipoproteins that appear to participate in adhesion (including the previously characterised Lmb protein), protein export and folding, enzymes and several species-specific proteins of unknown function . These data suggest lipoproteins may have significant roles that influence the virulence of this important pathogen.

J Bacteriol, 2004 Apr, 186(7), 2046 - 51
Hydrogen peroxide production in Streptococcus pyogenes: involvement of lactate oxidase and coupling with aerobic utilization of lactate; Seki M et al.; Streptococcus pyogenes strains can be divided into two classes, one capable and the other incapable of producing H2O2 (M . Saito, S . Ohga, M . Endoh, H . Nakayama, Y . Mizunoe, T . Hara, and S . Yoshida, Microbiology 147:2469-2477, 2001) . In the present study, this dichotomy was shown to parallel the presence or absence of H2O2-producing lactate oxidase activity in permeabilized cells . Both lactate oxidase activity and H2O2 production under aerobic conditions were detectable only after glucose in the medium was exhausted . Thus, the glucose-repressible lactate oxidase is likely responsible for H2O2 production in S . pyogenes . Of the other two potential H2O2-producing enzymes of this bacterium, NADH and alpha-glycerophosphate oxidase, only the former exhibited low but significant activity in either class of strains . This activity was independent of the growth phase, suggesting that the protein may serve in vivo as a subunit of the H2O2-scavenging enzyme NAD(P)H-linked alkylhydroperoxide reductase . The activity of lactate oxidase was associated with the membrane while that of NADH oxidase was in the soluble fraction, findings consistent with their respective physiological roles, i.e., the production and scavenging of H2O2 . Analyses of fermentation end products revealed that the concentration of lactate initially increased with time and decreased on glucose exhaustion, while that of acetate increased during the culture . These results suggest that the lactate oxidase activity of H2O2-producing cells oxidizes lactate to pyruvate, which is in turn converted to acetate . This latter process proceeds presumably via acetyl coenzyme A and acetyl phosphate with formation of extra ATP.

Br J Clin Pharmacol, 2004 Apr, 57(4), 500 - 5
Acute otitis media in children: a retrospective analysis of physician prescribing patterns; Quach C et al.; BACKGROUND: Acute otitis media (AOM) is one of the most common infectious diseases of childhood and the most frequent indication for antibiotic use in children . Aim To better understand the prescribing patterns and appropriateness of AOM therapy . METHODS: We investigated a historical cohort of children aged < or = 6 years who had a first AOM episode between June 1999 and June 2002, using the Regie de l'assurance maladie du Quebec (RAMQ) administrative databases . Conformity of prescription was based on the consensus guidelines on AOM treatment from the Drug-resistant Streptococcus pneumoniae Therapeutic Working Group . These recommendations suggested amoxicillin as the first-line drug, and amoxicillin-clavulanic acid or cefuroxime for children who had received antibiotics in the previous month . Data were analysed using descriptive statistics, chi(2) test and logistic regression . RESULTS: During the study period, 60 513 children < or = 6 years of age experienced their first AOM episode with a mean age of 2.6 years . They were seen by 4708 physicians {87% general practitioners (GPs), 9% paediatricians, and 3% ENT specialists} . Amoxicillin was the antibiotic that was prescribed the most (43%), followed by cefprozil and azithromycin . Overall, 42% of physicians adhered to antibiotic guideline recommendations . Compared with GPs, paediatricians were almost as likely to prescribe in conformity with the consensus guidelines, whereas ENT specialists were 50% less likely to prescribe an antibiotic recommended by the guidelines . CONCLUSION: Continuing medical education is necessary to ensure appropriate adherence to antibiotic guidelines.

J Oral Rehabil, 2004 Mar, 31(3), 278 - 85
Adherence of Streptococcus mutans to various restorative materials in a continuous flow system; Eick S et al.; A continuous flow system was developed to evaluate the adhesion of Streptococcus mutans ATCC 25175 to filling materials (Ariston, Tetric, Dyract, Compoglass, Vitremer, Aqua Ionofil, Ketac Fil, amalgam, Galloy and ceramics as controls) . Streptococcus mutans was added to saliva-coated test specimens, and a nutrient broth permanently supplied over a time period of 48 h and then the weight of plaque, the number and viability of the bacteria adhering to the materials were determined . The weights of artificial plaque on all filling materials tested were higher than those on ceramics, the highest values were measured on the glass-ionomers . The amount of plaque correlates with the surface roughness, whereas there was no correlation of the surface roughness with the number of colony-forming units (CFU) of S . mutans . The CFU of adhering S . mutans also depends on the viability of the bacteria . The plaque on Ketac Fil contained a high number of viable bacteria . The fluorides of glass-ionomers do not efficiently prevent the attachment and the viability of S . mutans.

Curr Opin Infect Dis, 2004 Apr, 17(2), 127 - 30
Pneumonia in the elderly; Loeb M; PURPOSE OF REVIEW: This review provides an update on new data about the etiology, clinical characteristics, outcomes, and prevention of community-acquired pneumonia . The impact of severe acute respiratory syndrome in older persons is also addressed . RECENT FINDINGS: Streptococcus pneumoniae remains the most important cause of community-acquired pneumonia in the very elderly (80 years and over) . Pneumococcus is also an important etiologic agent of pneumonia in residents of long-term care facilities . Clinical signs and symptoms of community-acquired pneumonia are less distinct in this group compared with younger patients . New data about influenza immunization reveal better mucosal immunity with the intranasal vaccine compared with the intramuscular vaccine . A review of clinical trial evidence differs from observational studies that demonstrate a clear benefit of the polysaccharide pneumococcal vaccine in the elderly . The prospect of severe acute respiratory syndrome in older adults is the most important new issue to emerge, as older adults are at increased risk from complications and death . SUMMARY: There are many challenges in preventing and managing community-acquired pneumonia in the elderly . S . pneumoniae remains the most important cause . The clinical presentation of pneumonia in the very elderly can be nonspecific . Given the safety profile of the vaccine and supportive observational evidence, public health policymakers should continue to support use of the polysaccharide pneumococcal vaccine . However, research into new vaccine strategies, including use of conjugate or common antigen vaccines, is a priority.

Hua Xi Kou Qiang Yi Xue Za Zhi, 2004 Feb, 22(1), 10 - 2
{Expression of GBD gene of Streptococcus mutans glucan binding protein A in mammalian cells}; Su LY et al.; OBJECTIVE: To evaluate the expression of recombinant plasmid pcDNA3.1/GBD of glucan binding protein of Streptococcus mutans in mammalian cells COS-7 . METHODS: Eukaryotic plasmid carrying encoding gene of GBD of Streptococcus mutans gbpA was constructed and the plasmid was introduced into COS-7 cells by Lipofectamine reagent . The transient expressed protein in COS-7 cells was detected by immunochemistry technique . RESULTS: The positive expression was detected in plasma of the cells which were transfected with recombinant plasmid pcDNA3.1/GBD . The cells which were transfected with pcDNA3.1 were negative . CONCLUSION: GBD can translate and express in COS-7 cells after transfected with recombinant plasmid pcDNA3.1/GBD . The expressed protein locates in the plasma and the protein is able to combine with anti-GbpA antibody . The expressed protein has the antigenicity and is a candidate gene vaccine.

Proc Natl Acad Sci U S A, 2004 Mar 23, 101(12), 4250 - 5 Epub 2004 Mar 11.
Bacterial biota in the human distal esophagus; Pei Z et al.; The esophagus, like other luminal organs of the digestive system, provides a potential environment for bacterial colonization, but little is known about the presence of a bacterial biota or its nature . By using broad-range 16S rDNA PCR, biopsies were examined from the normal esophagus of four human adults . The 900 PCR products cloned represented 833 unique sequences belonging to 41 genera, or 95 species-level operational taxonomic units (SLOTU); 59 SLOTU were homologous with culture-defined bacterial species, 34 with 16S rDNA clones, and two were not homologous with any known bacterial 16S rDNA . Members of six phyla, Firmicutes, Bacteroides, Actinobacteria, Proteobacteria, Fusobacteria, and TM7, were represented . A large majority of clones belong to 13 of the 41 genera (783/900, 87%), or 14 SLOTU (574/900, 64%) that were shared by all four persons . Streptococcus (39%), Prevotella (17%), and Veilonella (14%) were most prevalent . The present study identified approximately 56-79% of SLOTU in this bacterial ecosystem . Most SLOTU of esophageal biota are similar or identical to residents of the upstream oral biota, but the major distinction is that a large majority (82%) of the esophageal bacteria are known and cultivable . These findings provide evidence for a complex but conserved bacterial population in the normal distal esophagus.

Cell, 2004 Feb 6, 116(3), 367 - 79
M protein, a classical bacterial virulence determinant, forms complexes with fibrinogen that induce vascular leakage; Herwald H et al.; Increased vascular permeability is a key feature of inflammatory conditions . In severe infections, leakage of plasma from the vasculature induces a life-threatening hypotension . Streptococcus pyogenes, a major human bacterial pathogen, causes a toxic shock syndrome (STSS) characterized by excessive plasma leakage and multi-organ failure . Here we find that M protein, released from the streptococcal surface, forms complexes with fibrinogen, which by binding to beta2 integrins of neutrophils, activate these cells . As a result, neutrophils release heparin binding protein, an inflammatory mediator inducing vascular leakage . In mice, injection of M protein or subcutaneous infection with S . pyogenes causes severe pulmonary damage characterized by leakage of plasma and blood cells . These lesions were prevented by treatment with a beta2 integrin antagonist . In addition, M protein/fibrinogen complexes were identified in tissue biopsies from a patient with necrotizing fasciitis and STSS, further underlining the pathogenic significance of such complexes in severe streptococcal infections.

Eur J Clin Pharmacol, 2004 Apr, 60(2), 115 - 9 Epub 2004 Mar 10.
The geographic relationship between the use of antimicrobial drugs and the pattern of resistance for Streptococcus pneumoniae in Italy; Boccia D et al.; OBJECTIVES: A temporal relationship between the increasing use of antibiotics and the increasing levels of antibiotic resistance has been established for Streptococcus pneumoniae . There are also data that support the presence of a geographic correlation between the level of resistance and the pattern of use among different countries and even within the same country . The aim of this study was to evaluate the potential geographic correlation between the use of beta-lactams and erythromycin in different Italian regions and the resistance of these antibiotics to invasive strains of S . pneumoniae during the period 1999-2000 . METHODS: Ecological study . RESULTS: In Italy the mean level of resistance for penicillin and erythromycin was 11.4% and 28.9%, respectively . The highest level of resistance for both antibiotics was observed in central and southern regions (i.e . Campania, Lazio and the combined regions of Calabria, Puglia and Sicilia) . These regions were also those with the highest consumption of antibiotics . A strong correlation was found between the prevalence of resistance to erythromycin and the regional use of macrolides (r=0.93, P=0.001) and beta-lactams (r=0.84, P=0.002) . With regard to penicillin resistance, the greatest correlation was observed for oral penicillin (r=0.85, P=0.002) . CONCLUSION: Our study provides further evidence of the association between regional level of antibiotic use and prevalence of antibiotic resistance.

Int J Antimicrob Agents, 2004 Feb, 23(2), 181 - 96
In vitro activity of gemifloxacin and contemporary oral antimicrobial agents against 27247 Gram-positive and Gram-negative aerobic isolates: a global surveillance study; Bouchillon SK et al.; This study was a multi-centre, multi-country surveillance of 27247 Gram-positive and Gram-negative isolates collected from 131 study centres in 44 countries from 1997 to 2000 . MICs of gemifloxacin were compared with penicillin, amoxicillin-clavulanic acid, cefuroxime, azithromycin, clarithromycin, trimethoprim-sulphamethoxazole, ciprofloxacin, grepafloxacin and levofloxacin by broth microdilution . Penicillin resistance in Streptococcus pneumoniae was extremely high in the Middle East (65.6%), Africa (64.0%) and Asia (60.4%) and lower in North America (40.3%), Europe (36.9%) and the South Pacific (31.8%) . Macrolide resistance in S . pneumoniae was highest in Asia (51.7%) but varied widely between laboratories in Europe (26.0%), North America (21.6%), the Middle East (13.7%), the South Pacific (10.6%) and Africa (10.0%) . All the study quinolones were highly active against penicillin-resistant and macrolide-resistant S . pneumoniae . Overall, gemifloxacin had the lowest MIC(90) at 0.06 mg/l with MICs 4-64-fold lower than ciprofloxacin, levofloxacin and grepafloxacin against S . pneumoniae . Gemifloxacin MICs were more potent than grepafloxacin > levoflaxacin > ciproflaxin against the Gram-positive aerobes and shared comparable Gram-negative activity with ciprofloxacin and levofloxacin.

Mol Microbiol, 2004 Mar, 51(6), 1661 - 75
A two-component system that controls the expression of pneumococcal surface antigen A (PsaA) and regulates virulence and resistance to oxidative stress in Streptococcus pneumoniae; McCluskey J et al.; Recent genomic-based studies have identified 13 two-component signal transduction systems (TCS) in Streptococcus pneumoniae . Bacterial TCSs are important for regulating expression of bacterial genes, including those which are important to the virulence of pathogenic bacteria . We have used virulence assays together with microarray analysis to investigate the importance of pneumococcal TCS04 in the virulence and gene regulation of this pathogen . Deletion mutants of the response regulator of TCS04, rr04, were examined in three independent pneumococcal strains representing three different pneumococcal serotypes . Analysis of the virulence of the three strains enabled us to identify a serotype-specific attenuation of virulence due to deletion of rr04 . Microarray comparison of the transcriptional profiles of the wild-type strains with the rr04 mutants allowed us to determine which transcriptional changes were occurring in the rr04 mutants . Virulence-associated changes were demonstrated in the attenuated strain with significant downregulation of a previously determined virulence locus, psaB, psaC and psaA.

Mol Microbiol, 2004 Mar, 51(6), 1641 - 8
The D,D-carboxypeptidase PBP3 organizes the division process of Streptococcus pneumoniae; Morlot C et al.; Bacterial division requires the co-ordination of membrane invagination, driven by the constriction of the FtsZ-ring, and concomitant cell wall synthesis, performed by the high-molecular-weight penicillin-binding proteins (HMW PBPs) . Using immunofluorescence techniques, we show in Streptococcus pneumoniae that this co-ordination requires PBP3, a D,D-carboxypeptidase that degrades the substrate of the HMW PBPs . In a mutant deprived of PBP3, the apparent rings of HMW PBPs and that of FtsZ are no longer co-localized . In wild-type cells, PBP3 is absent at the future division site and present over the rest of the cell surface, implying that the localization of the HMW PBPs at mid-cell depends on the availability of their substrate . FtsW, a putative translocase of the substrate of the PBPs, forms an apparent ring that is co-localized with the septal HMW PBPs throughout the cell cycle of wild-type cells . In particular, the constriction of the FtsW-ring occurs after that of the FtsZ-ring, with the same delay as the constriction of the septal PBP-rings . However, in the absence of PBP3, FtsW remains co-localized with FtsZ in contrast to the HMW PBPs . Our work reveals an unexpected complexity in the relationships between the division proteins . The consequences of the absence of PBP3 indicate that the peptidoglycan composition is central to the co-ordination of the division process.

J Paediatr Child Health, 2004 Apr, 40(4), 184 - 8
Invasive pneumococcal disease in the Australian Capital Territory and Queanbeyan region: do high infant rates reflect more disease or better detection?
Andresen DN, Collignon PJ.
OBJECTIVE: To describe the epidemiology of invasive pneumococcal disease in the Australian Capital Territory (ACT) and Queanbeyan region prior to the introduction of conjugate pneumococcal vaccines . METHODOLOGY: Residents with sterile site isolates of Streptococcus pneumoniae from 1998 to 2000 were identified from a prospective bacteraemia surveillance project involving all ACT public hospitals, supplemented by retrospective laboratory-based detection of other sterile site isolates . RESULTS: Incidence of invasive pneumococcal disease was 15.2 cases per 105 per year, and 193.4 per 105 per year in infants under 2 years . Primary bacteraemia was significantly more common in infants and young children than in older subjects . Reduced penicillin susceptibility was observed in 9.6% of isolates, and no high-level penicillin resistance was observed . CONCLUSIONS: Infants in the ACT and Queanbeyan have a higher invasive pneumococcal disease incidence than similar populations worldwide . Better detection is the most likely explanation . This population would be ideal for studies of the 'real life' effectiveness of infant conjugate vaccination.

Clin Exp Immunol, 2004 Mar, 135(3), 483 - 9
Serum and salivary IgA antibody responses to Saccharomyces cerevisiae, Candida albicans and Streptococcus mutans in orofacial granulomatosis and Crohn's disease; Savage NW et al.; Orofacial granulomatosis (OFG) is a condition of unknown aetiology with histological and, in some cases, clinical association with Crohn's disease (CD) . However, the exact relationship between OFG and CD remains uncertain . The aim of this study was to determine whether OFG could be distinguished immunologically from CD by comparing non-specific and specific aspects of humoral immunity in serum, whole saliva and parotid saliva in three groups of patients: (a) OFG only (n = 14), (b) those with both oral and gut CD (OFG + CD) (n = 12) and (c) CD without oral involvement (n = 22) and in healthy controls (n = 29) . Non-specific immunoglobulin (IgA, SigA, IgA subclasses and IgG) levels and antibodies to whole cells of Saccharomyces cerevisiae, Candida albicans and Streptococcus mutans were assayed by enzyme-linked immunosorbent assay (ELISA) in serum, whole saliva and parotid saliva . Serum IgA and IgA1 and IgA2 subclasses were raised in all patient groups (P < 0.01) . Salivary IgA (and IgG) levels were raised in OFG and OFG + CD (P < 0.01) but not in the CD group . Parotid IgA was also raised in OFG and OFG + CD but not in CD . The findings suggest that serum IgA changes reflect mucosal inflammation anywhere in the GI tract but that salivary IgA changes reflect involvement of the oral cavity . Furthermore, the elevated levels of IgA in parotid saliva suggest involvement of the salivary glands in OFG . Serum IgA antibodies to S . cerevisiae were raised markedly in the two groups with gut disease while serum IgA (or IgG) antibodies to C . albicans were elevated significantly in all three patient groups (P < 0.02) . No differences were found with antibodies to S . mutans . Whole saliva IgA antibodies to S . cerevisiae (and C . albicans) were raised in the groups with oral involvement . These findings suggest that raised serum IgA antibodies to S . cerevisiae may reflect gut inflammation while raised SIgA antibodies to S . cerevisiae or raised IgA or IgA2 levels in saliva reflect oral but not gut disease . Analysis of salivary IgA and IgA antibodies to S . cerevisiae as well as serum antibodies in patients presenting with OFG may allow prediction of gut involvement.

Jpn J Antibiot, 2003 Dec, 56(6), 712 - 8
{Clinical efficacy of oral clarithromycin monotherapy in patients with mild or moderate community-acquired pneumonia}; Fujiki R et al.; Clarithromycin (CAM) is a new macrolide antibiotic which is active against a wide range of organisms responsible for community-acquired pneumonia (CAP) and has superior pharmacokinetics and tolerance compared to erythromycin . In this study, we evaluated the clinical efficacy and antimicrobial activity of CAM in the empirical treatment of patients with CAP . CAM (200 mg given twice daily for 2 weeks) was orally administered to 26 patients with mild or moderate suspected atypical pneumonia, including 15 patients in whom treatment with beta-lactam antibiotics was largely ineffective . Causative pathogens were identified on the basis of quantitative sputum cultures, blood cultures, and routine serological testings; M . pneumoniae was most commonly observed in patients with CAP (38.5%; 10/26), followed by H . influenzae (11.5%; 3/26), C . pneumoniae (3.8%; 1/26), and S . constellatus (3.8%; 1/26) . Penicillin-resistant, or penicillin-susceptible Streptococcus pneumoniae were isolated from 1 patient (3.8%) and 2 patients (7.7%), respectively out of 26 patients with CAP . There were no detectable pathogens in 8 of 26 patients . The treatment of CAM resulted in complete resolution of all signs and symptoms of pneumonia in all the patients and was not accompanied with any adverse events . The overall incidence of laboratory abnormalities was not detectable in the patients evaluated . Although it is important to make differential diagnosis of atypical from bacterial pneumonia in designing therapeutic strategy, it is often difficult to make an appropriate diagnosis in patients with CAP . Because of diagnostic difficulties, CAM with a broad antimicrobial spectrum is recommended as the first-line drug for the treatment of lower respiratory infections, particularly in patients with suspected atypical pneumonia.

Chest, 2004 Mar, 125(3), 965 - 73
Steady-state intrapulmonary concentrations of moxifloxacin, levofloxacin, and azithromycin in older adults; Capitano B et al.; STUDY OBJECTIVE: To determine the steady-state, extracellular, and intracellular pulmonary disposition of moxifloxacin (MXF), levofloxacin (LEVO), and azithromycin (AZI) relative to that of the plasma over a 24-h dosing interval . DESIGN: Randomized, multicenter, open-label investigation . PATIENTS: Forty-seven older adults (mean {+/- SD} age, 62 +/- 13 years) undergoing diagnostic bronchoscopy . INTERVENTIONS: Oral administration of MXF, 400 mg, LEVO, 500 mg daily for five doses, or AZI, 500 mg for one dose, then 250 mg daily for four doses . BAL and venipuncture were completed at 4, 8, 12, or 24 h following the administration of the last dose . MEASUREMENTS AND RESULTS: Steady-state MXF, LEVO, and AZI concentrations were determined in the plasma, epithelial lining fluid (ELF), and alveolar macrophages (AMs) . The concentrations of all three agents were greatest in the AMs followed by the ELF compared to the plasma . Plasma concentrations were similar to those previously reported with these agents . The mean ELF concentrations at 4, 8, 12, and 24 h were as follows: MXF, 11.7 +/- 11.9, 7.8 +/- 5.1, 10.5 +/- 3.7, and 5.7 +/- 6.3 micro g/mL, respectively; LEVO, 15.2 +/- 4.5, 10.2 +/- 6.7, 6.9 +/- 4.4, and 2.9 +/- 1.7 micro g/mL, respectively; and AZI, 0.6 +/- 0.4, 0.7 +/- 0.4, 0.9 +/- 0.5, and 0.9 +/- 0.7 micro g/mL, respectively . The AM concentrations at 4, 8, 12, and 24 h were as follows: MXF, 47.7 +/- 47.6, 123.3 +/- 126.4, 26.2 +/- 19.4, and 32.8 +/- 16.5 micro g/mL, respectively; LEVO, 28.5 +/- 30.2, 26.1 +/- 15.7, 28.3 +/- 12.6, and 8.2 +/- 6.1 micro g/mL, respectively; and AZI, 71.8 +/- 50.1, 73.8 +/- 75.3, 155.9 +/- 81.3, and 205.2 +/- 256.3 micro g/mL, respectively . CONCLUSIONS: The intrapulmonary concentrations of MXF, LEV, and AZI were superior to those obtained in the plasma . The AM concentrations of all agents studied were more than adequate relative to the minimum concentration required to inhibit 90% of the organism population (MIC(90)) of the common intracellular pathogens (< 1 micro g/mL) . These data indicate that attainable extracellular concentrations of AZI are insufficient to reliably eradicate Streptococcus pneumoniae, based on the agent's current minimum inhibitory concentration profile, whereas the mean concentrations of MXF and LEVO in the ELF exceed the MIC(90) of the S pneumoniae population . Moreover, MXF concentrations exceeded the S pneumoniae susceptibility breakpoint (1.0 micro g/mL) at all time points, while 2 of 15 concentrations (13%) failed to maintain LEVO concentrations above the breakpoint (2.0 micro g/mL) throughout the dosing interval.

J Biomol Screen, 2004 Feb, 9(1), 3 - 11
A strategy for discovery of novel broad-spectrum antibacterials using a high-throughput Streptococcus pneumoniae transcription/translation screen; Pratt SD et al.; The authors report the development of a high-throughput screen for inhibitors of Streptococcus pneumoniae transcription and translation (TT) using a luciferase reporter, and the secondary assays used to determine the biochemical spectrum of activity and bacterial specificity . More than 220,000 compounds were screened in mixtures of 10 compounds per well, with 10,000 picks selected for further study . False-positive hits from inhibition of luciferase activity were an extremely common artifact . After filtering luciferase inhibitors and several known classes of antibiotics, approximately 50 hits remained . These compounds were examined for their ability to inhibit Escherichia coli TT, uncoupled S . pneumoniae translation or transcription, rabbit reticulocyte translation, and in vitro toxicity in human and bacterial cells . One of these compounds had the desired profile of broad-spectrum biochemical activity in bacteria and selectivity versus mammalian biochemical and whole-cell assays.

BMC Pregnancy Childbirth . 2004 Jan 27;4(1):1.
Cerebral palsy and placental infection: a case-cohort study; Vigneswaran R et al.; BACKGROUND: The association between cerebral palsy in very preterm infants and clinical, histopathologic and microbiological indicators of chorioamnionitis, including the identification of specific micro-organisms in the placenta, was evaluated in a case-cohort study . METHODS: Children with a diagnosis of cerebral palsy at five years of age were identified from amongst participants in a long-term follow-up program of preterm infants . The comparison group was a subcohort of infants randomly selected from all infants enrolled in the program . The placentas were examined histopathologically for chorioamnionitis and funisitis, and the chorioamnionic interface was aseptically swabbed and comprehensively cultured for aerobic and anaerobic bacteria, yeast and genital mycoplasmas . Associations between obstetric and demographic variables, indicators of chorioamnionitis and cerebral palsy status were examined by univariate analysis . RESULTS: Eighty-two infants with cerebral palsy were compared with the subcohort of 207 infants . Threatened preterm labor was nearly twice as common among the cases as in the subcohort (p < 0.01) . Recorded clinical choroamnionitis was similar in the two groups and there was no difference in histopathologic evidence of infection between the two groups . E . coli was cultured from the placenta in 6/30 (20%) of cases as compared with 4/85 (5%) of subcohort (p = 0.01) . Group B Streptococcus was more frequent among the cases, but the difference was not statistically significant . CONCLUSIONS: The association between E . coli in the chorioamnion and cerebral palsy in preterm infants identified in this study requires confirmation in larger multicenter studies which include microbiological study of placentas.

Eur J Ophthalmol, 2004 Jan-Feb, 14(1), 59 - 60
Endogenous group G Streptococcus endophthalmitis following a dental procedure; Ziakas NG et al.; PURPOSE: To report a case of bilateral endogenous endophthalmitis due to group G Streptococcus after a dental procedure . METHODS: Case report of a 69-year-old woman who presented with pain, decreased vision, bilateral uveitis, and a unilateral hypopyon 1 week after treatment for an abscessed tooth . RESULTS: Bilateral endophthalmitis was diagnosed, and group G Streptococcus was cultured from the vitreous samples . CONCLUSIONS: To our knowledge, this is the second reported case of endogenous endophthalmitis following a dental procedure . Furthermore, it was due to group G Streptococcus, which is a rare cause of this condition.

J Clin Microbiol, 2004 Mar, 42(3), 1360 - 2
Development of a diagnostic PCR assay targeting the Mn-dependent superoxide dismutase gene (sodA) for identification of Streptococcus gallolyticus; Sasaki E et al.; A PCR-based assay to identify Streptococcus gallolyticus has been developed . The assay uses an oligonucleotide primer pair targeting a partial sequence of the manganese-dependent superoxide dismutase gene (sodA) . The assay distinguished members of the S . gallolyticus group from other, closely related taxa successfully by yielding a 408-bp specific amplicon.

J Clin Microbiol, 2004 Mar, 42(3), 1326 - 9
Multiplex PCR assay for direct identification of group B streptococcal alpha-protein-like protein genes; Creti R et al.; We developed a group B streptococcus multiplex PCR assay which allows, by direct analysis of the amplicon size, determination of the surface protein antigen genes of alpha-C protein, epsilon protein, Rib, Alp2, Alp3, and Alp4 . The multiplex PCR assay offers a rapid and simple method of subtyping Streptococcus agalactiae based on surface protein genes.

J Clin Microbiol, 2004 Mar, 42(3), 1274 - 6
Comparison of the Denka Seiken slide agglutination method to the quellung test for serogrouping of Streptococcus pneumoniae isolates; Shutt CK et al.; This study compared a slide agglutination test (Denka Seiken, Tokyo, Japan) to the "gold standard" quellung reaction (Pneumotest; Statens Serum Institut, Copenhagen, Denmark) for the serogrouping of pneumococci . Two hundred clinical isolates of Streptococcus pneumoniae were used for the comparison . Each assay was performed according to the manufacturer's instructions . There was an overall agreement of 95.7% between the two methods . Only 4 of 10 isolates of serogroup 22 were detected with the slide agglutination assay . Two isolates that were untypeable by the Pneumotest method were typed as serogroups 6 and 31 by the slide agglutination method . The Pneumotest method was unable to type 22 isolates, and the slide agglutination method was unable to type 16 isolates . The slide agglutination method compares favorably with the Pneumotest method and is easier to perform and to interpret.

J Clin Microbiol, 2004 Mar, 42(3), 1263 - 4
Resistance of group B streptococcus to selected antibiotics, including erythromycin and clindamycin; Heelan JS et al.; Resistance of group B streptococcus (GBS) to antibiotics, particularly erythromycin and clindamycin, was studied . Erythromycin resistance was present in 22% of GBS isolates, and these isolates were constitutively resistant, inducibly resistant, or sensitive to clindamycin . Erythromycin and clindamycin MICs were related to the presence of ermA, ermB, or mefA genes.

J Clin Microbiol, 2004 Mar, 42(3), 1192 - 8
Characterization of three new enterococcal species, Enterococcus sp . nov . CDC PNS-E1, Enterococcus sp . nov . CDC PNS-E2, and Enterococcus sp . nov . CDC PNS-E3, isolated from human clinical specimens; Carvalho Mda G et al.; As a reference laboratory, the Streptococcus Laboratory at the Centers for Disease Control and Prevention (CDC) is frequently asked to confirm the identity of unusual or difficult-to-identify catalase-negative, gram-positive cocci . In order to accomplish the precise identification of these microorganisms, we have systematically applied analysis of whole-cell protein profiles (WCPP) and DNA-DNA reassociation experiments, in conjunction with conventional physiological tests . Using this approach, we recently focused on the characterization of three strains resembling the physiological groups I (strain SS-1730), II (strain SS-1729), and IV (strain SS-1728) of enterococcal species . Two strains were isolated from human blood, and one was isolated from human brain tissue . The results of physiological testing were not consistent enough to allow confident inclusion of the strains in any of the known enterococcal species . Resistance to vancomycin was detected in one of the strains (SS-1729) . Analysis of WCPP showed unique profiles for each strain, which were not similar to the profiles of any previously described Enterococcus species . 16S ribosomal DNA (rDNA) sequencing results revealed three new taxa within the genus ENTEROCOCCUS: The results of DNA-DNA relatedness experiments were consistent with the results of WCPP analysis and 16S rDNA sequencing, since the percentages of homology with all 25 known species of Enterococcus were lower than 70% . Overall, the results indicate that these three strains constitute three new species of Enterococcus identified from human clinical sources, including one that harbors the vanA gene . The isolates were provisionally designated Enterococcus sp . nov . CDC Proposed New Species of Enterococcus 1 (CDC PNS-E1), type strain SS-1728(T) (= ATCC BAA-780(T) = CCUG 47860(T)); Enterococcus sp . nov . CDC PNS-E2, type strain SS-1729(T) (= ATCC BAA-781(T) = CCUG 47861(T)); and Enterococcus sp . nov . CDC PNS-E3, type strain SS-1730(T) (= ATCC BAA-782(T) = CCUG 47862(T)).

Vaccine, 2004 Mar 12, 22(9-10), 1157 - 61
Antibody response to pneumolysin and to pneumococcal capsular polysaccharide in healthy individuals and Streptococcus pneumoniae infected patients; Huo Z et al.; Background: Animal experiments have shown that antibodies against capsular polysaccharide enhance phagocytosis of pneumococcal bacteria and that antibodies against pneumolysin are anti-inflammatory and prevent pneumococcal invasion . It is not known if an antibody response to pneumolysin can be acquired from natural exposure to pneumococcal bacteria or how the concentration of pneumolysin antibody at the mucosal surface compares with that of antibodies against pneumococcal capsular polysaccharide . This study used an equal potency method to measure specific antibody concentrations against pneumolysin and pneumococcal capsular polysaccharides in order to facilitate comparative estimates of concentrations in saliva and serum . The results may provide experimental information as a basis for an improved pneumococcal vaccine strategy . Results: Healthy individuals had higher IgM and IgG antibody concentrations against capsular polysaccharide than against pneumolysin in both saliva and serum, but for IgA the converse was true . Patients with acute pneumococcal infection had significantly lower concentrations of specific IgG antibodies against both antigens than the healthy group . These patients also had significantly higher concentrations of IgM antibody against both antigens than the healthy control group . Discussion: Healthy individuals acquire a comparatively lower concentration of antibody to pneumolysin than to pneumococcal capsular polysaccharides from natural exposure to pneumococcal bacteria . Patients infected by pneumococcal bacteria have lower specific IgG antibody concentrations to both antigens than healthy individuals . These findings support the view that pneumolysin could potentially be used as a vaccine . For enhanced effectiveness, it could be used as a supplement to Pneumovax((R))II rather than as a replacement . The two acquired antibodies, i.e . to pneumolysin and to capsular polysaccharide, could then play their protective roles at different stages in the course of pneumococcal infection, and together contribute to an effective immune defence against Streptococcus pneumoniae.

J Clin Periodontol, 2003 Dec, 30(12), 1017 - 23
Relationship between tongue coating and secretory-immunoglobulin A level in saliva obtained from patients complaining of oral malodor; Hinode D et al.; AIM: The aim of this study was to confirm the relationships between oral malodor and periodontal condition, oral malodor and tongue coating, and to investigate the secretory-immunoglobulin A (S-IgA) level in saliva in relation to the accumulation of tongue coating . METHODS: Fifty-four patients complaining of oral malodor were included in the study . Their periodontal conditions, tongue coating status and salivary characteristics (flow rate, protein and S-IgA concentrations) were assessed in addition to the level of volatile sulfur compounds (VSC) in oral cavity . The patients were divided into three groups according to their tongue coating level . RESULTS: There are significant relationships between oral malodor and specific periodontal parameters used . The degree of tongue coating was also significantly correlated with the amount of H2S, CH3SH and the total amount of VSC determined . The concentration of S-IgA in the group identified as slight tongue coating was significantly higher than in the moderate or the severe group . By Western immunoblotting analysis, a high level of S-IgA specific to Streptococcus species was recognized in all groups, whereas the reactivity of Porphyromonas gingivalis and Fusobacterium nucleatum with S-IgA was very weak in both the slight and the moderate groups . CONCLUSION: Data herein indicate that tongue coating is closely related to oral malodor . Furthermore, S-IgA in saliva may influence the accumulation of tongue coating, and S-IgA antibodies directed to Streptococcus species may play a role in protective immunity against the initial colonization of tongue plaque.

Lancet, 2004 Feb 28, 363(9410), 696 - 703
Effect of a bacterial pheromone peptide on host chemokine degradation in group A streptococcal necrotising soft-tissue infections; Hidalgo-Grass C et al.; BACKGROUND: Necrotising soft-tissue infections due to group A streptococcus (GAS) are rare (about 0.2 cases per 100000 people) . The disease progresses rapidly, causing severe necrosis and hydrolysis of soft tissues . Histopathological analysis of necrotic tissue debrided from two patients (one with necrotising fasciitis and one with myonecrosis) showed large quantities of bacteria but no infiltrating neutrophils . We aimed to investigate whether the poor neutrophil chemotaxis was linked with the ability of group A streptococcus (GAS) to degrade host chemokines . METHODS: We did RT-PCR, ELISA, and dot-blot assays to establish whether GAS induces synthesis of interleukin 8 mRNA, but subsequently degrades the released chemokine protein . Class-specific protease inhibitors were used to characterise the protease that degraded the chemokine . We used a mouse model of human soft-tissue infections to investigate the pathogenic relevance of GAS chemokine degradation, and to test the therapeutic effect of a GAS pheromone peptide (SilCR) that downregulates activity of chemokine protease . FINDINGS: The only isolates from the necrotic tissue were two beta-haemolytic GAS strains of an M14 serotype . A trypsin-like protease released by these strains degraded human interleukin 8 and its mouse homologue MIP2 . When innoculated subcutaneously in mice, these strains produced a fatal necrotic soft-tissue infection that had reduced neutrophil recruitment to the site of injection . The M14 GAS strains have a missense mutation in the start codon of silCR, which encodes a predicted 17 aminoacid pheromone peptide, SilCR . Growth of the M14 strain in the presence of SilCR abrogated chemokine proteolysis . When SilCR was injected together with the bacteria, abundant neutrophils were recruited to the site of infection, bacteria were cleared without systemic spread, and the mice survived . The therapeutic effect of SilCR was also obtained in mice challenged with M1 and M3 GAS strains, a leading cause of invasive infections . INTERPRETATION: The unusual reduction in neutrophils in necrotic tissue of people with GAS soft-tissue infections is partly caused by a GAS protease that degrades interleukin 8 . In mice, degradation can be controlled by administration of SilCR, which downregulates GAS chemokine protease activity . This downregulation increases neutrophil migration to the site of infection, preventing bacterial spread and development of a fulminant lethal systemic infection.

Comp Immunol Microbiol Infect Dis, 2004 May, 27(3), 217 - 23
Development of a sandwich-dot enzyme linked immunosorbent assay for Streptococcus pneumoniae antigen detection in cerebrospinal fluid; Rai GP et al.; A new sandwich dot-enzyme linked immunosorbent assay (sdot-ELISA) was developed using omniserum prepared against different strains of Streptococcus pneumoniae as capture antibody and also as second or revealing antibody after its conjugation with horseradish peroxidase (HRP) for detection of pneumococcal antigen in cerebrospinal fluid (CSF) . A total of 103 CSF samples of different categories were screened with newly developed dot-ELISA and results were compared with commercially available latex agglutination (LA) kit . The newly developed sdot-ELISA was more sensitive than LA test and can be used as an alternative diagnostic tool in laboratory and in field conditions . An added advantage of this ELISA system was that it did not require antibodies produced in two different animal species.

J Infect, 2004 Apr, 48(3), 229 - 35
Streptococcus pneumoniae and Streptococcus pyogenes isolated from a paediatric population in Great Britain and Ireland: the in vitro activity of telithromcycin versus comparators; Shackcloth J et al.; OBJECTIVES: To investigate the antimicrobial susceptibility profiles of clinical isolates of Streptococcus pneumoniae and Streptococcus pyogenes, isolated from children within Great Britain and Ireland (Northern Ireland and Eire), with particular reference to the new oral ketolide telithromycin . To determine the distribution of macrolide resistance genes within the erythromycin resistant population . METHODS: MICs were determined using NCCLS microbroth dilution methodology and macrolide resistance mechanisms were investigated using PCR . RESULTS: Penicillin susceptibility was found to be 92.6% in S . pneumoniae isolates ( n=831; 3.7% intermediate, MIC 0.12-1 mg/l, 3.7% resistant, MIC >2.0 mg/l) and 100% in S . pyogenes isolates (n=1333) 8.8% of S . pneumoniae and 2.5% of S . pyogenes isolates demonstrated erythromycin-A resistance (EryA(R)) . One hundred percent of S . pneumoniae and 99.8% of S . pyogenes isolates were susceptible to telithromycin (MIC<or=1.0 mg/l) . Of the 73 EryA(R) S . pneumoniae isolates tested, 55 (75.3%) were mef (A) positive, 17 (23.3%) erm (B) positive and one isolate (1.4%) was positive for both mechanisms . Of the 34 isolates of EryA(R) S . pyogenes tested, 23 (67.6%) were erm (A) subclass erm (TR) positive, 4 (11.8%) erm (B) and 7 (20.6%) mef (A) positive . CONCLUSIONS: This paper presents baseline data on penicillin and macrolide resistance in S . pneumoniae and S . pyogenes isolates in the paediatric population of Great Britain and Ireland . Telithromycin, recently approved for the treatment of community acquired respiratory tract infections (CARTI) in patients over 12 years of age throughout the European community, demonstrated high in vitro activity against these pathogens, including EryA(R) strains.

Microb Drug Resist, 2003 Winter, 9(4), 345 - 51
Typing and molecular characterization of Streptococcus pneumoniae with reduced susceptibility to cefotaxime isolated in Latin America; Castanheira M et al.; The treatment of systemic infections, especially meningitis, caused by Streptococcus pneumoniae nonsusceptible to third-generation cephalosporins, is extremely difficult due to the paucity of therapeutic options . The main objective of this study was to characterize isolates of S . pneumoniae with reduced susceptibility to cefotaxime (MICs, > or = 1 microg/ml) by different typing methods and to evaluate whether clonal dissemination of this pathogen had occurred among Latin American medical centers . A total of 46 isolates collected from respiratory tract specimens, blood cultures, cerebrospinal fluid, eye, and other sources were analyzed . The isolates were collected from Latin American medical centers located in Argentina, Brazil, Chile, Colombia, Mexico, and Uruguay through two multicenter surveillance programs, in 1997 and 1998 . Isolates were serotyped and molecular typed by pulsed-field gel electrophoresis (PFGE) and automated ribotyping . Antimicrobial susceptibilities were determined to 19 drugs by reference broth microdilution methods . Ten isolates (21.7%) had cefotaxime MICs > or = 2 microg/ml, whereas 36 (78.3%) had cefotaxime MIC results at 1 microg/ml . All isolates were susceptible to gatifloxacin, levofloxacin, and vancomycin . The isolates were distributed among five major serotypes (%): 23F (39.1%), 14 (32.6%), 19F (23.9%), 9V (2.2%), and 6B (2.2%) . However, distinct molecular patterns were detected among isolates with a unique serotype . Six and four PFGE patterns were identified among isolates with serotype 23F and 19F, respectively . When PFGE and automated ribotyping analyses were combined, four clusters were identified . The largest cluster (10 isolates) was represented by isolates with ribotype 18-2, major PFGE pattern I, and serotype 14 . ATCC 700671 (international clone Spain 9V-3) also showed ribotype 18-2 . This clone was detected in four countries: Argentina, Brazil, Chile, and Uruguay . A second cluster (8 isolates) were characterized by isolates with ribotype 17-4, PFGE type D, and serotype 23F, similar to ATCC 700669 (international clone Spain23F-1) . Isolates from this cluster were identified in three countries: Brazil, Chile, and Mexico . Our results indicated that clonal dissemination of S . pneumoniae with reduced susceptibility to cefotaxime has occurred in Latin America mainly among serogroups 14, 19F, and 23F.

Scand J Infect Dis, 2004, 36(1), 63 - 5
Group A streptococcus bacteraemia complicated by osteomyelitis in an immunocompetent adult; Akesson P et al.; Osteomyelitis due to group A streptococcus is an unusual complication of varicellae in children . We report the first case of group A streptococcus bacteraemia complicated by multifocal osteomyelitis in an adult.

Clin Infect Dis, 2004 Mar 15, 38(6), 836 - 42 Epub 2004 Mar 01.
Differences in potency of intravenous polyspecific immunoglobulin G against streptococcal and staphylococcal superantigens: implications for therapy of toxic shock syndrome; Darenberg J et al.; Administration of intravenous polyspecific immunoglobulin G (IVIG) has been proposed as adjunctive therapy for toxic shock syndrome caused by Streptococcus pyogenes or Staphylococcus aureus . We investigated whether superantigen-containing culture supernatants prepared from streptococcal isolates (n=21) and staphylococcal isolates (n=20) from cases of severe sepsis were inhibited to an equal extent by IVIG in proliferation experiments that used human peripheral blood mononuclear cells . All 3 IVIG preparations tested were highly efficient in neutralizing the superantigens, and most supernatants were completely inhibited at concentrations ranging from 0.05 to 2.5 mg IVIG/mL . An important finding was that culture supernatants from S . pyogenes isolates were consistently inhibited to a greater extent than those of S . aureus isolates (P<.01) . The findings demonstrate that staphylococcal superantigens are not inhibited as efficiently as streptococcal superantigens by IVIG, and, hence, a higher dose of IVIG may be required for therapy of staphylococcal toxic shock syndrome in order to achieve protective titers and clinical efficacy.

Clin Infect Dis, 2004 Mar 15, 38(6), 830 - 5 Epub 2004 Feb 27.
Clinical manifestations and molecular epidemiology of necrotizing pneumonia and empyema caused by Streptococcus pneumoniae in children in Taiwan; Hsieh YC et al.; Recently, there have been increasing numbers of pneumococcal pneumonia cases, with their associated complications . We conducted a retrospective review to increase the understanding of childhood pneumococcal pneumonia . Seventy-one patients with pneumococcal pneumonia were identified . Forty (56.3%) of them developed complicated pneumonia . Multivariate analysis showed that presence of immature polymorphonuclear leukocytes in peripheral blood (odds ratio {OR}, 3.67; 95% confidence interval {CI}, 1.08-12.63), high C-reactive protein levels (>12 mg/dL) (OR, 5.24; 95% CI, 1.10-24.93), and no underlying disease at presentation (OR, 5.48; 95% CI, 1.06-28.25) were independent predictors of the occurrence of necrosis or/and abscess . Fourteen isolates (35%), which were genotypically identical and had the same pulsed-field gel electrophoresis pattern (serogroup 14, with MICs of penicillin of 0.1-0.5 mu g/mL), were significantly associated with complicated pneumonia (P=.047) . Whether the virulence of antibiotic-resistant pneumococci is evolving deserves further investigation.

Clin Infect Dis, 2004 Mar 15, 38(6), 787 - 98 Epub 2004 Mar 01.
Drug-resistant pneumococcal pneumonia: clinical relevance and related factors; Aspa J et al.; A multicenter study of 638 cases of community-acquired pneumonia due to Streptococcus pneumoniae (SP-CAP) was performed to assess current levels of resistance . Of the pneumococcal strains, 35.7% had an minimum inhibitory concentration (MIC) of penicillin of > or =0.12 microg/mL (3 isolates had an MIC of 4 microg/mL), 23.8% had an MIC of erythromycin of 128 microg/mL, and 22.2% were multidrug resistant . Logistic regression determined that chronic pulmonary disease (odds ratio {OR}, 1.44}, human immunodeficiency virus infection (OR, 1.98), clinically suspected aspiration (OR, 2.12), and previous hospital admission (OR, 1.69) were related to decreased susceptibility to penicillin, and previous admission (OR, 1.89) and an MIC of penicillin of MIC > or =0.12 microg/mL (OR, 15.85) were related to erythromycin resistance (MIC, > or =1 microg/mL) . The overall mortality rate was 14.4% . Disseminated intravascular coagulation, empyema, and bacteremia were significantly more frequent among patients with penicillin-susceptible SP-CAP . Among isolates with MICs of penicillin of > or =0.12 microg/mL, serotype 19 was predominant and was associated with a higher mortality rate . In summary, the rate of resistance to beta -lactams and macrolides among S . pneumoniae that cause CAP remains high, but such resistance does not result in increased morbidity.

J Infect Dis, 2004 Mar 15, 189(6), 1097 - 102 Epub 2004 Feb 27.
Multilocus sequence typing of serotype III group B streptococcus and correlation with pathogenic potential; Davies HD et al.; Serotype III group B streptococcus (GBS) causes more invasive disease in infants than do other serotypes in North America . We used multilocus sequence typing to identify clones within 28 invasive serotype III GBS isolates identified from a population-based study and 55 serotype III GBS colonizing isolates from a cohort of women from the same population . Ten allelic sequence types (STs) were identified and primarily involved 2 profiles: ST-19 (57.1% of invasive isolates and 58.2% of colonizing isolates) and ST-17 (32.1% of invasive isolates and 29.1% of colonizing isolates) . On concatenation, the 10 allelic profiles converged into 3 groups . Group 1 consisted of ST-19 complex, ST-36, and ST-1, and was closely related to reference genome 2603V/R (serotype V) . Group 2 consisted of ST-17 complex . Group 3 consisted of ST-23 complex and was closely related to the serotype III genome strain NEM 316 . Neither of the major sequence types or groups was more commonly associated with invasion (P=.61) or with lower levels of maternal capsular polysaccharide-specific IgG (0.89 microg/mL and 0.39 microg/mL, respectively) for ST-19 and ST-17 (P=.86) . The close association of genomic strain 2603V/R (serotype V) with ST-19 suggests that the phenomenon of capsule switching may have occurred.

Lancet Infect Dis, 2004 Mar, 4(3), 144 - 54
Streptococcus pneumoniae colonisation: the key to pneumococcal disease; Bogaert D et al.; Streptococcus pneumoniae is an important pathogen causing invasive diseases such as sepsis, meningitis, and pneumonia . The burden of disease is highest in the youngest and oldest sections of the population in both more and less developed countries . The treatment of pneumococcal infections is complicated by the worldwide emergence in pneumococci of resistance to penicillin and other antibiotics . Pneumococcal disease is preceded by asymptomatic colonisation, which is especially high in children . The current seven-valent conjugate vaccine is highly effective against invasive disease caused by the vaccine-type strains . However, vaccine coverage is limited, and replacement by non-vaccine serotypes resulting in disease is a serious threat for the near future . Therefore, the search for new vaccine candidates that elicit protection against a broader range of pneumococcal strains is important . Several surface-associated protein vaccines are currently under investigation . Another important issue is whether the aim should be to prevent pneumococcal disease by eradication of nasopharyngeal colonisation, or to prevent bacterial invasion leaving colonisation relatively unaffected and hence preventing the occurrence of replacement colonisation and disease . To illustrate the importance of pneumococcal colonisation in relation to pneumococcal disease and prevention of disease, we discuss the mechanism and epidemiology of colonisation, the complexity of relations within and between species, and the consequences of the different preventive strategies for pneumococcal colonisation.

J Bacteriol, 2004 Mar, 186(6), 1902 - 4
Analysis of an agmatine deiminase gene cluster in Streptococcus mutans UA159; Griswold AR et al.; An operon encoding enzymes of the agmatine deiminase system (AgDS) has been identified in the cariogenic bacterium Streptococcus mutans UA159 . The AgDS is regulated by agmatine induction and carbohydrate catabolite repression . Ammonia is produced from agmatine at low pH, suggesting that the AgDS could augment acid tolerance.

Lupus, 2004, 13(2), 77 - 84
Vascular and connective tissue diseases in the paediatric world; Falcini F; Despite the fact that in recent decades many advances have been made in classification, outcomes measurements and therapeutic regimens, connective tissue diseases remain a challenge for paediatric rheumatologists . Corticosteroids are still the first choice therapy in juvenile systemic lupus erythematosus (SLE); however, it is time for a new therapeutic approach with immunosuppressant drugs in order to obtain a more prolonged survival and reduced organ system damage . A prevention of relapse of thromboembolic phenomena using low-dose aspirin is strongly suggested in children with anticardiolipin antibodies, particularly in those with SLE . The long-term prognosis in juvenile dermatomyositis is significantly improved due to a more aggressive treatment with corticosteroids and methotrexate . The treatment of Henoch-Schoenlein purpura is still under debate, and no agreement has been reached regarding the role of corticosteroids in the prevention of renal involvement . The management of the acute phase of Kawasaki disease is now well established, although there is controversy regarding the role of corticosteroids . It is still under debate how and whether to treat patients who do not fulfil the diagnostic criteria . Polyarteritis nodosa is a disease at risk of death and requires an aggressive approach with corticosteroids and immunosuppressants, while cutaneous polyarteritis needs a close control of an underlying streptococcus infection and prophylaxis with benzatin-penicillin to prevent relapses.

Shanghai Kou Qiang Yi Xue, 2001 Mar, 10(1), 49 - 51
{Base composition of DNA from fluoride resistant strains of streptococcus mutans and streptococcus sobrinus}; Sheng JY et al.; OBJECTIVES: To evaluate the genotype change of fluoride-resistant strains of S.mutans and S.sobrinus . METHODS: High potential liquid chromatography was used to measure the base composition of DNA from F-resistant strains of S.mutans and S.sobrinus and their parent strains . RESULTS: The data showed that the DNA G+C mol% of F-resistant and F-sensitive S.mutans were quite different, the difference was over 5% . The four F-resistant strains were 54.45, 44.86, 54.41, 55, 390, whereas the corresponding four parent strains were 35.38, 37.4, 43.35, 46.62, respectively . CONCLUSION: The genotypes of F-resistant strains of S.mutans and S.sobrinus have been changed and may comprise several gene mutations.

Acta Crystallogr D Biol Crystallogr, 2004 Mar, 60(Pt 3), 528 - 30 Epub 2004 Feb 25.
Purification, crystallization and preliminary X-ray analysis of native and selenomethionine class I tagatose-1,6-bisphosphate aldolase from Streptococcus pyogenes; Liotard B et al.; Tagatose-1,6-bisphosphate aldolase (EC 4.1.2.40) is situated at the branching of the tagatose-6-phosphate and Embden-Meyerhof-Parnas (glycolysis) metabolic pathways, where it catalyzes the reversible cleavage of tagatose-1,6-bisphosphate to dihydroxyacetone phosphate and glyceraldehyde 3-phosphate . The recombinant protein from Streptococcus pyogenes was overexpressed in Escherichia coli in its native and selenomethionine-derivative forms and purified using ion-exchange and hydrophobic interaction chromatography . Orthorhombic crystals suitable for structural analysis were obtained by the hanging-drop vapour-diffusion method for both isoforms . The crystals belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 63.7, b = 108.1, c = 238.7 A for the native form and a = 64.1, b = 108.3, c = 239.8 A for the selenomethionine derivative . The asymmetric unit contains four protomers, corresponding to a crystal volume per protein weight (V(M)) of 2.8 A(3) Da(-1) and a solvent content of 56% by volume.

Pediatrics, 2004 Mar, 113(3 Pt 1), e168 - 72
Temporal association of the appearance of mucoid strains of Streptococcus pyogenes with a continuing high incidence of rheumatic fever in Utah; Veasy LG et al.; OBJECTIVE: Our objective was to confirm an observed temporal association of increased numbers of rheumatic fever cases concomitant with the appearance of an increased prevalence of mucoid strains of Streptococcus pyogenes . During the resurgence of rheumatic fever (RF) that has occurred in the Intermountain area surrounding Salt Lake City, Utah, since 1985, the largest number of cases occurred in 1985 and 1986 and 12 years later in 1997 and 1998 . During the initial outbreak and the later exacerbation of the resurgence, an increased number of mucoid strains of S pyogenes were present in the community . METHODS: The referred cases of RF that fulfilled Jones criteria have been systematically reviewed by the medical staff at Primary Children's Medical Center yearly since 1985 . Before the resurgence of RF, a program was initiated by the microbiology laboratory at Primary Children's Medical Center to store frozen isolates of S pyogenes . All frozen specimens were randomly selected and entered into a log; the coded entry allowed for comments regarding the origin of the isolate and whether the isolate had a mucoid appearance on the blood agar culture plate . This log was reviewed in October 2002 to determine whether the percentage of frozen mucoid isolates stored during the resurgence of RF would support the clinical and epidemiologic suspicion that mucoid isolates seemed to be present with a higher frequency during the 2 periods of high incidence of RF . The percentage of mucoid isolates was compared with the yearly number of cases of RF . A Pearson r correlation analysis was completed to determine whether there was a significant association between the percentage of mucoid isolates and the number of cases of RF . RESULTS: The highest number of cases of RF was temporally associated with the highest percentage of mucoid isolates . There was statistically significant correlation between percentage of mucoid strains and the number of RF cases . CONCLUSIONS: The Utah experience with the resurgence of RF in a civilian population during the last decade and a half of the 20th century confirmed the temporal association of mucoid strains of S pyogenes, primarily M-type 18, with a high incidence of RF.

Pediatrics, 2004 Mar, 113(3 Pt 1), 443 - 9
Decrease of invasive pneumococcal infections in children among 8 children's hospitals in the United States after the introduction of the 7-valent pneumococcal conjugate vaccine; Kaplan SL et al.; OBJECTIVE: To monitor clinical and microbiologic features including antimicrobial susceptibility and serogroup distribution of invasive infections caused by Streptococcus pneumoniae among children before and after the introduction of routine administration of the 7-valent pneumococcal conjugate vaccine (PCV7) . DESIGN: A 9-year (January 1, 1994 through December 31, 2002) prospective surveillance study of all invasive pneumococcal infections in children . PATIENTS: Infants and children cared for at 8 children's hospitals in the United States with culture-proven invasive infections caused by S pneumoniae . RESULTS: When compared with the mean of the years 1994 to 2000, the annual number of invasive pneumococcal infections for children < or =24 months of age declined 58% in 2001 and 66% in 2002 . If only the serogroups in the PCV7 are considered, the number of cases in children < or =24 months old declined 63% and 77% in 2001 and 2002, respectively . The greatest decrease was observed for serogroup-14 isolates . The number of isolates in nonvaccine serogroups increased 28% in 2001 and 66% in 2002 for children < or =24 months old . Nonvaccine serogroup-15 and -33 isolates had the greatest increase in number . The proportion of all isolates nonsusceptible to penicillin increased yearly from 1994 to 2000, reached a plateau in 2001 at 45%, and declined to 33% in 2002 . Decrease in nonsusceptibility to penicillin occurred entirely in the isolates with penicillin minimum inhibitory concentration > or =2 microg/mL . Nonsusceptibility to penicillin increased slightly among nonvaccine-serotype isolates . Most infections after at least 2 doses of PCV7 were caused by nonvaccine-serotype isolates . CONCLUSIONS: Since the introduction of the PCV7, the number of invasive pneumococcal infections caused by vaccine-serogroup isolates among 8 US children's hospitals has decreased >75% among children < or =24 months old . In addition, penicillin resistance decreased in 2002 for the first time since our surveillance began in 1993-1994 . However, we have noted that replacement may be developing with serogroups 15 and 33 . Furthermore, penicillin resistance seems to be increasing among nonvaccine serogroups . Surveillance must be continued to detect the emergence of changes in the distribution of serotypes as well as antibiotic susceptibility.

J Biol Chem, 2004 May 14, 279(20), 21421 - 30 Epub 2004 Mar 01.
Pulmonary surfactant protein A augments the phagocytosis of Streptococcus pneumoniae by alveolar macrophages through a casein kinase 2-dependent increase of cell surface localization of scavenger receptor A; Kuronuma K et al.; Pulmonary surfactant proteins A (SP-A) and D (SP-D), members of the collectin family, play important roles in the innate immune system of the lung . Here, we show that SP-A but not SP-D augmented phagocytosis of Streptococcus pneumoniae by alveolar macrophages, independent of its binding to the bacteria . Analysis of the SP-A/SP-D chimeras, in which progressively longer carboxyl-terminal regions of SP-A were replaced with the corresponding SP-D regions, has revealed that the SP-D region Gly(346)-Phe(355) can be substituted for the SP-A region Leu(219)-Phe(228) without altering the SP-A activity of enhancing the phagocytosis and that the SP-A region Cys(204)-Cys(218) is required for the SP-A-mediated phagocytosis . Acetylated low density lipoprotein significantly reduced the SP-A-stimulated uptake of the bacteria . SP-A failed to enhance the phagocytosis of S . pneumoniae by alveolar macrophages derived from scavenger receptor A (SR-A)-deficient mice, demonstrating that SP-A augments SRA-mediated phagocytosis . Preincubation of macrophages with SP-A at 37 degrees C but not at 4 degrees C stimulated the phagocytosis . The SP-A-mediated enhanced phagocytosis was not inhibited by the presence of cycloheximide . SP-A increased cell surface localization of SR-A that was inhibitable by apigenin, a casein kinase 2 (CK2) inhibitor . SP-A-treated macrophages exhibited significantly greater binding of acetylated low density lipoprotein than nontreated cells . The SP-A-stimulated phagocytosis was also abolished by apigenin . In addition, SP-A stimulated CK2 activity . These results demonstrate that SP-A enhances the phagocytosis of S . pneumoniae by alveolar macrophages through a CK2-dependent increase of cell surface SR-A localization . This study reveals a novel mechanism of bacterial clearance by alveolar macrophages.

Clin Cornerstone, 2003, Suppl 3, S4 - 11
Resistance issues and community-acquired respiratory infections; Sahm DF; Antimicrobial resistance, associated with both excessive and inappropriate use of antimicrobial agents, is a global problem . It is a particular problem in the management of community-acquired respiratory infections, which most often result in the use of antimicrobial therapy . Infections caused by resistant and multiresistant pathogens may also result in high hospitalization rates, long lengths of stay, severe illness, and high mortality, all of which have a great impact on health care costs . The Tracking Resistance in the United States Today (TRUST) Program, the largest longitudinal continuous-surveillance program of its kind, has been conducted every year since 1996 and tracks consecutive respiratory seasons on a year-to-year basis to monitor resistance patterns of respiratory pathogens . This article discusses some of the findings of the TRUST Program, particularly trends in Streptococcus pneumoniae resistance.

Eur J Immunol, 2004 Mar, 34(3), 850 - 8
The human antibody response to pneumococcal capsular polysaccharides is dependent on the CD40-CD40 ligand interaction; Jeurissen A et al.; Protection against infections with Streptococcus pneumoniae is mediated by antibodies against the capsular polysaccharides (caps-PS) . Here we show that in in vitro experiments CD4+ T lymphocytes stimulate and CD8+ T lymphocytes inhibit the human anti-caps-PS antibody response . Using antagonistic anti-CD40 and antagonistic anti-CD40 ligand (CD40L) monoclonal antibodies, we showed that the CD4+ T lymphocyte-mediated stimulation is dependent on the CD40-CD40L interaction . The role of CD40L was further illustrated by the observation that CD4+ T lymphocytes obtained from a patient with hyper-IgM syndrome were unable to enhance the immune response to caps-PS . Furthermore, CD4+ T lymphocytes from cord blood, which did not express CD40L in response to stimulation with caps-PS, failed to stimulate the antibody response of adult B lymphocytes to caps-PS . These in vitro findings were confirmed by in vivo experiments in which SCID/SCID mice were reconstituted with human mononuclear cells . Furthermore, we showed that caps-PS induce production of IL-4, IL-6, IL-10, and IFN-gamma, and that this enhanced production was inhibited by blocking the CD40-CD40L interaction . This is the first demonstration that the human immune response to caps-PS, which is markedly regulated by T lymphocytes, is dependent on the CD40-CD40L interaction.

J Infect Chemother, 2004 Feb, 10(1), 11 - 8
Human THP-1 monocyte uptake and cellular disposition of 14C-grepafloxacin; Hall IH et al.; Uptake of (14)C-grepafloxacin into human mononuclear (THP-1) cells was determined at pH 7.4, 6.8, or 5.0 over a 4-log antibiotic concentration . Grepafloxacin was taken up by THP-1 monocytes rapidly by both a passive and an active transport mechanism at pH 7.4 . Its uptake was initially linear, with equilibrium being reached after approximately 1 h . Efflux followed first-order clearance and was complete within 1 h, suggesting no longterm sequestering of the antibiotic occurred . Neither cell number nor serum protein binding appeared to have any effect on antibiotic uptake . High intracellular concentrations were achieved and the ratios of cellular to extracellular antibiotic concentration (IC/EC) were between 529 and 644 at 0.04 micro g/ml at pH 7.4 and 6.8, suggesting that monocytes may contain sufficient levels of grepafloxacin for affecting bacteriostatic killing . Grepafloxacin disposition within the THP-1 monocytes showed large amounts present in the nucleus and cell sap in stimulated and unstimulated cells, and its presence was evenly distributed throughout the cytosol, nuclei, lysosomes, mitochondria, and ribosomes . After stimulation by zymogen A, Staphylococcus aureus, or Streptococcus pneumoniae, increased amounts of grepafloxacin were found within THP-1 monocytes and isolated phagosome vacuoles . No antibiotic sequestration occurred inside stimulated monocytes, although a sufficient intracellular grepafloxacin concentration was available to kill phagocytized bacteria . Metabolic inhibitors, suppressors of K(+)/Cl(-) and Cl(-) transporters, inhibitors of the phagocytic process, low temperature, and low pH inhibited grepafloxacin uptake by THP-1 monocytes.

Zhonghua Er Ke Za Zhi, 2004 Jan, 42(1), 16 - 9
{Antibiotics-resistance pattern and genetic type of Streptococcus pneumoniae isolated from children in Hangzhou}; Hua CZ et al.; OBJECTIVE: To investigate the antibiotics-resistance type and molecular epidemiology of Streptococcus pneumoniae isolated from children in Hangzhou . METHODS: The sensitivities of 323 strains of Streptococcus pneumoniae to 9 antibiotics were determined in vitro by Kirby-Bauer diffuse methods, and MICs of penicillin and cefotaxime were determined by E-test methods . RESULTS: Among all 323 strains isolated from children during the period from August 2001 to July 2002, 136 strains (42.1%) were sensitive to penicillin, while 57 strains (17.7%) were penicillin-resistant . Penicillin MICs ranged from 0.012 microg/ml to 4.0 microg/ml . All the strains were sensitive to cefotaxime and its MICs ranged from 0.012 microg/ml to 4.0 microg/ml . The most resistant antibiotic was erythromycin and it's resistant-rate was as high as 90.7%, followed by tetracycline (87.6%), trimethoprim-sulfamethoxazole (48.6%) and chloromycetin (14.9%) . Totally 197 strains (61.0%) were multi-drug-resistant pneumococci and most of them were resistant to trimethoprim-sulfamethoxazole, erythromycin and tetracycline at the same time . Two strains (0.6%) were resistant to rifampin and none was resistant to vancomycin and ofloxacin . BOX PCR typing was carried out and no overwhelming fingerprinting pattern was found among penicillin resistant Streptococcus pneumoniae strains which were isolated from patients, while the banding patterns were always similar or identical among the strains isolated from the same specimen or from the same patient at different time, respectively . CONCLUSION: The antibiotics-resistant rate of pneumococci was high in Hangzhou, but the third-generation cephalosporins were still the best antibiotics against Streptococcus pneumoniae . One child could be infected or colonized by more than one pneumococci clone at the same or different time.

Zhonghua Nei Ke Za Zhi, 2004 Jan, 43(1), 33 - 6
{A clinical analysis of 70 cases of infective endocarditis}; Wang HL et al.; OBJECTIVE: To investigate the clinical characteristics, therapeutical approaches and outcome of infective endocarditis (IE) . METHODS: The clinical features, diagnosis, treatment and outcome of 70 IE patients who were treated in Peking Union Medical College Hospital from January 1988 to May 2000 were analyzed . RESULTS: Of the 70 consecutive cases who were diagnosed as IE according to the Duke's new criteria . 38 patients were male and 32 patients female . The average age was (36.1 +/- 16.6) years old . 8 cases were prosthetic valve endocarditis (PVE) and 62 cases native valve endocarditis (NVE) . 57 of the 62 (91.9%) NVE patients had pre-existing cardiac abnormalities predisposing to IE, such as congenital cardiovascular disease (22 cases), idiopathic mitral valve prolapse (18 cases), rheumatic heart disease (12 cases), senile degenerative heart disease (3 cases), and permanent pacemaker (PM) implantation 2 cases . Fever (100%), anemia (57.1%) and embolism (47.1%) were the three most common clinical manifestations . Of the 42 cases who had a positive blood culture result, Streptococcus vividans (54.8%) was the most common isolated microorganism . 39 out of the 51 cases receiving antimicrobial therapy and 17 of the 19 cases being treated with combination of antibiotics and surgery were cured . 14 cases including 5 PVE and 2 IE after PM implantation died with a mortality rate of 20% . Intractable congestive heart failure was the leading cause of death . CONCLUSIONS: Congenital cardiovascular diseases and idiopathic mitral valve prolapse were the two most commonly found underlying heart diseases . Blood culture and echocardiogram should always be done to evaluate the possibility of IE while a patient presents with fever of unknown origin, especially when he or she has anemia or embolism . PVE, IE after PM implantation and intractable congestive heart failure were associated with a poor prognosis.

Drugs Today (Barc), 1998 Aug, 34(8), 691 - 8
Antibiotic resistance; Cunha BA; Antibiotic resistance is an increasing problem in many parts of the world . Antibiotic resistance has been associated with the use of some antibiotics but not with others . Due to the overuse of antibiotics with a high resistance potential, there has been an increase of resistance with certain bacteria, e.g., Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pneumoniae . This article discusses the antibiotics associated with a high resistance potential and those that are safe to use with a low resistance potential . Strategies for minimizing antibiotic resistance are discussed.

Infez Med, 2003 Dec, 11(4), 213 - 5
Drawbacks of antibiotic susceptibility of Streptococcus pneumoniae; Pasticci MB et al.; During 10 years penicillin resistance among clinical isolates of S . pneumoniae was more or less stable . The cumulative proportion of penicillin non susceptible S . pneumoniae (PNSP) was 13.0%; 7.2% when isolates with MIC = 2 mg/l were considered . Among PNSP only 2 strains were isolated from sterile body fluids, one having MIC >3.84 mg/l . Lack of susceptibility to cotrimoxazole was 38.4% . All isolates were susceptible to ceftriaxone, levofloxacin, moxifloxacin, and quinupristin-dalfopristin.

Infez Med, 2003 Dec, 11(4), 189 - 95
{Streptococcus bovis infectious endocarditis: clinical and epidemiological characteristics}; Massaroni K et al.; This paper shows our experience concerning the study of Streptococcus bovis infectious endocarditis (EI): 47 patients, with no prior history of IV drug abuse (NTD), who suffered EI caused by Streptococcus bovis were excerpted from a case record of 1053 cases with diagnosis of EI defined in accordance with Duke's Hospital criteria . For each patient we considered age, sex, complications, echocardiographic findings, antibiotic therapy, eventual heart-surgery and final outcome of the disease . We then compared the parameters of our patients, with the ones of 216 NTD patients suffering non Streptococcus bovis EI, selected according to age correspondence and concomitant onset of the disease . The characteristics of Streptococcus bovis EI are analogous to the ones of EIs caused by other micro-organisms in NTD patients, except for a non statistically significant trend of higher frequency in old age and in males . Concerning possible predisposing conditions, we considered the association extensively described in the literature between Streptococcus bovis EI and gastroenteric pathology (above all colon neoplasms): this association was not frequently observed in our study because appropriate instrumental investigations of the digestive tract were carried out only in a minority of patients.

Clin Infect Dis, 2004 Mar 1, 38(5), 632 - 9 Epub 2004 Feb 17.
Nasopharyngeal carriage of Streptococcus pneumoniae by adults and children in community and family settings; Regev-Yochay G et al.; The rate of Streptococcus pneumoniae carriage among adults was compared with that among children (age, < or =6 years) in the same population . Nasopharyngeal culture results for 1300 adults and 404 children were analyzed . S . pneumoniae was carried by only 4% of the adults, compared with 53% of children in the same community . Young age, day care center attendance, having young siblings, and no antibiotic use during the month before screening were associated with the high carriage rate among children, whereas the only risk factor associated with carriage among adults was the presence of a respiratory infection on the screening day . S . pneumoniae serotype distribution and antibiotic resistance patterns differed between adults and children . Isolates of the same serotype--even of the same clone--differed in their antibiotic susceptibility patterns between children and adults . In a subanalysis of 151 pairs of children and their parents and of 32 pairs of siblings, intrafamilial transmission of S . pneumoniae could not be demonstrated.

MMWR Morb Mortal Wkly Rep, 2004 Feb 27, 53(7), 152 - 4
Effect of new susceptibility breakpoints on reporting of resistance in Streptococcus pneumoniae--United States, 2003; Centers for Disease Control and Prevention (CDC); In January 2003, the National Committee for Clinical Laboratory Standards (NCCLS) finalized new breakpoints for defining the susceptibility of Streptococcus pneumoniae isolates to cefotaxime and ceftriaxone . The former breakpoints were based on attainable concentrations of these antibiotics in cerebrospinal fluid (CSF) and the level at which it was thought that meningitis treatment failed because of elevated minimum inhibitory concentrations (MICs) . The new breakpoints differ for S . pneumoniae isolates causing meningitis and those causing nonmeningeal clinical syndromes . To assess the effect of these new criteria on reporting of nonsusceptible S . pneumoniae isolates, CDC analyzed cefotaxime MIC data from the Active Bacterial Core Surveillance (ABCs) of the Emerging Infections Program (EIP) Network during 1998-2001 . This report summarizes the results of that analysis, which indicated that after the new criteria were applied, the number of isolates defined as nonsusceptible to cefotaxime decreased 52.1%-61.2% for each year . Laboratory reports for clinicians should include interpretations using the new breakpoints for meningitis and nonmeningeal syndromes for all non-CSF isolates.

Pediatr Neurol, 2004 Feb, 30(2), 107 - 10
Anti-brain antibodies in PANDAS versus uncomplicated streptococcal infection; Pavone P et al.; The objective of this study was to assess brain involvement through the presence of antineuronal antibodies in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) and in uncomplicated active Group A streptococcal infection . We compared serum antibrain antibody to human basal ganglia sections assessed by indirect tissue immunofluorescence in two groups: a PANDAS group, comprised of 22 patients (mean age 10.1 years; 20 male, 2 female) who met strict National Institutes of Mental Health diagnostic criteria for PANDAS and had clinically active tics or obsessive-compulsive disorder, or both; and a GABHS control group consisting of 22 patients (mean age 9.1 years; 15 mol/L, 7 female) with clinical evidence of active Group A beta-hemolytic streptococcal (GABHS) infection confirmed by throat culture and elevated antistreptolysin O titers but without history or clinical evidence of tics or obsessive-compulsive disorder . We observed positive anti-basal ganglia staining (defined as detectable staining at 1:10 serum dilution) in 14/22 patients in the PANDAS group (64%) but only 2/22 (9%) in the GABHS control group (P < 0.001, Fisher's exact test) . These results suggest that antibrain antibodies are present in children with PANDAS that cannot be explained merely by a history of GABHS infection.

Acta Paediatr Taiwan, 2003 Nov-Dec, 44(6), 343 - 8
Clinical analysis of necrotizing pneumonia in children: three-year experience in a single medical center; Chen KC et al.; Necrotizing pneumonia (NP) is a rare but complex complication of lobar pneumonia in children . It is characterized by massive necrosis and liquification of lung tissues by the presence of multiple cavities rather than a solitary one . To evaluate the clinical features of NP, we enrolled 17 patients at Chang-Gung Memorial Hospital (Kaohsiung) from November 1999 to December 2002 . The diagnosis of NP was based upon findings of chest computed tomography . There were six boys and 11 girls, ages ranging from 47 days to seven years . Streptococcus pneumoniae was the most common pathogen responsible for 9 cases in our study . Our patients remained febrile, even with the appropriate antibiotics administered, for a mean of 12.1 +/- 5.2 days and hospitalized for a mean of 22.7 +/- 7.0 days . The right lung was affected more than the left (12:7) . On admission, laboratory data showed either leukocytosis, or normal leukocyte count, or leukopenia, but C-reactive protein was abnormally high (mean = 304.8 +/- 96.3 mg/L) . Anemia and significant platelet count elevation developed at a mean period of 8.5 +/- 3.5 and 10.9 +/- 4.7 days after their hospitalization, respectively . Surgical intervention was performed in one case only in our series . Chest roentgenography took a mean of 60.3 +/- 15.6 days to resolve completely . Although the clinical course was prolonged, all patients with NP eventually recovered completely with no sequela.

Shanghai Kou Qiang Yi Xue, 2002 Mar, 11(1), 50 - 2
{The in vitro study on Polistes mandarinus' effects on cariogenic bacteria}; Huang ZW et al.; OBJECTIVE:To study the role of Polistes mandarinus on the growth,acid generation and water insoluble glucan(WIG) production of Streptococcus mutans, Streptococcus sanguis and Actinomyces viscosus as a preparation for screening an effective agent ot medicate the balance of oral microflora . METHODS: Streptococcus mutans 3a3, Streptococcus sanguis SB 179 and Actinomyces viscosus ATCC 19246 were chosen as the experimental bacteria.The effects of Polistes mandarinus on the growth, acid generation and glucan production were observed . RESULTS: Polistes mandarinus can inhibit the growth and acid generation of S.mutans,S.sanguis and A.viscosus, and the water-insoluble glucan production of S.mutants and S.sanguis effectively . CONCLUSION: Polistes mandarinus can inhibit the growth, acid generation and glucan production of oral bacteria effectively.

Shanghai Kou Qiang Yi Xue, 2002 Jun, 11(2), 141 - 2
{The inhibitory effect of anti-streptococcus mutans immunoglobulin of yolk on glucan synthesis of Streptococcus mutans}; Wen B et al.; OBJECTIVES: To observe the inhibitory effect of anti-Streptococcus mutans Hen-egg-yolk (IgY) on glucan synthesis of Streptococcus mutans . METHODS: Determine the glucan with anthrone method after using the different titer of IgY on S.mutans and S.sobrinus . RESULTS: The inhibitory effect of antibody on S.mutans and S.sobrinus synthesis glucan had a similar tendency . The effect of inhibit glucan synthesis was influenced by the titer of antibody . High titer with high inhibition . Begin with the group of 1:16 titer, the group of 1:2 titer showed the highest inhibition (P<0.05) . CONCLUSION: The antibody can reduce synthesis of glucan from S.mutans and S.sobrinus.

Antimicrob Agents Chemother, 2004 Mar, 48(3), 961 - 9
Interactions between penicillin-binding proteins (PBPs) and two novel classes of PBP inhibitors, arylalkylidene rhodanines and arylalkylidene iminothiazolidin-4-ones; Zervosen A et al.; Several non-beta-lactam compounds were active against various gram-positive and gram-negative bacterial strains . The MICs of arylalkylidene rhodanines and arylalkylidene iminothiazolidin-4-ones were lower than those of ampicillin and cefotaxime for methicillin-resistant Staphylococcus aureus MI339 and vancomycin-resistant Enterococcus faecium EF12 . Several compounds were found to inhibit the cell wall synthesis of S . aureus and the last two steps of peptidoglycan biosynthesis catalyzed by ether-treated cells of Escherichia coli or cell wall membrane preparations of Bacillus megaterium . The effects of the arylalkylidene rhodanines and arylalkylidene iminothiazolidin-4-one derivatives on E . coli PBP 3 and PBP 5, Streptococcus pneumoniae PBP 2xS (PBP 2x from a penicillin-sensitive strain) and PBP 2xR (PBP 2x from a penicillin-resistant strain), low-affinity PBP 2a of S . aureus, and the Actinomadura sp . strain R39 and Streptomyces sp . strain R61 DD-peptidases were studied . Some of the compounds exhibited inhibitory activities in the 10 to 100 microM concentration range . The inhibition of PBP 2xS by several of them appeared to be noncompetitive . The dissociation constant for the best inhibitor (Ki = 10 microM) was not influenced by the presence of the substrate.

Antimicrob Agents Chemother, 2004 Mar, 48(3), 860 - 6
Effect of antibiotic treatment delay on therapeutic outcome of experimental acute otitis media caused by Streptococcus pneumoniae strains with different susceptibilities to amoxicillin; Parra A et al.; The effect of delayed administration of amoxicillin on the course of acute otitis media (AOM) caused by two Streptococcus pneumoniae strains with different susceptibilities to amoxicillin (MICs of 0.016 and 1 microg/ml for strains A and B, respectively) was evaluated in the gerbil model . The organisms were inoculated by transbullar challenge into the middle ear, and antibiotic treatment was administered at various times thereafter . The bacteriological and clinical efficacies of treatment diminished significantly with the delay of antibiotic administration . The bacterial eradication rates when antibiotic treatment was started at 2, 5, 8, 18, and 21 h post-bacterial inoculation were different for both strains (95, 95, 90, 55, and 55% for strain A and 95, 95, 65, 10, and 0% for strain B) . Results of further experiments using strain B with higher antibiotic doses and numbers of administrations and different follow-up times indicate that the failures observed with the delayed administration were not related to the bacterial burden, selection of antibiotic-resistant mutants, or inadequate pharmacodynamic parameters . Such failures may be related to the metabolic bacterial status . The delayed amoxicillin treatment of AOM caused by S . pneumoniae may lead to therapeutic failures, mainly when organisms with diminished antibiotic susceptibility are involved.

Antimicrob Agents Chemother, 2004 Mar, 48(3), 765 - 73
Activities of garenoxacin against quinolone-resistant Streptococcus pneumoniae strains in vitro and in a mouse pneumonia model; Azoulay-Dupuis E et al.; Garenoxacin is a novel des-F(6) quinolone with enhanced in vitro activities against both gram-positive and gram-negative bacteria . We compared the activity of garenoxacin with that of trovafloxacin (TVA) against Streptococcus pneumoniae, together with their efficacies and their capacities to select for resistant mutants, in a mouse model of acute pneumonia . In vitro, garenoxacin was more potent than TVA against wild-type S . pneumoniae and against a mutant with a single mutation (parC), a mutant with double mutations (gyrA and parC), and a mutant with triple mutations (gyrA, parC, and parE) . Swiss mice were infected with 10(5) CFU of virulent, encapsulated S . pneumoniae strain P-4241 or its derived isogenic parC, gyrA, gyrA parC, and efflux mutants and 10(7) CFU of poorly virulent clinical strains carrying a parE mutation or gyrA, parC, and parE mutations . The drugs were administered six times, every 12 h, beginning at either 3 or 18 h postinfection . The pulmonary pharmacokinetic parameters in mice infected with strain P-4241 and treated with garenoxacin or TVA (25 mg/kg of body weight) were as follows: maximum concentration of drug in serum (C(max); 17.3 and 21.2 micro g/ml, respectively), C(max)/MIC ratio (288 and 170, respectively), area under the concentration-time curve (AUC; 48.5 and 250 microg . h/ml, respectively), and AUC/MIC ratio (808 and 2000, respectively) . Garenoxacin at 25 and 50 mg/kg was highly effective (survival rates, 85 to 100%) against the wild-type strain and mutants harboring a single mutation . TVA was as effective as garenoxacin against these strains . TVA at 200 mg/kg and garenoxacin at 50 mg/kg were ineffective against the mutant with the parC and gyrA double mutations and the mutant with the gyrA, parC, and parE triple mutations . The efficacy of garenoxacin was reduced only when strains bore several mutations for quinolone resistance.

Respirology, 2004 Mar, 9(1), 109 - 14
Incidence of community-acquired pneumonia in children caused by Mycoplasma pneumoniae: serological results of a prospective, population-based study in primary health care; Korppi M et al.; OBJECTIVE: The objective of the present study was to assess the incidence of community-acquired pneumonia (CAP) in children caused by Mycoplasma pneumoniae . METHODOLOGY: During 12 months in 1981-1982, all CAP cases in a defined child population were registered . M . pneumoniae aetiology, initially measured by complement fixation (CF) test, was in 1999 supplemented by measurement of IgG and IgM antibodies using enzyme immunoassays (EIA) . RESULTS: M . pneumoniae was detected in 61 (30%) of 201 paediatric CAP cases, being the most common aetiological agent in those 5 years of age or over . At that age, M . pneumoniae was responsible for over 50% of cases, and over 90% of mycoplasmal cases were treated as outpatients . The EIA detected 17 new cases over and above the 44 detected by CF, while CF alone revealed 10 cases . The incidence of M . pneumoniae CAP increased with age, being over 10/1000 children at the age of 10 years or more . Co-infections with Streptococcus pneumoniae and Chlamydia pneumoniae were present in over 30% and 15%, respectively, of mycoplasmal CAP cases . CONCLUSION: M . pneumoniae is a common cause of paediatric CAP in primary health care, and co-infections with S . pneumoniae are common . Both S . pneumoniae and M . pneumoniae should be taken into account when starting antibiotics for children with CAP.

J Med Virol, 2004 Apr, 72(4), 517 - 24
Pneumonia in HIV-infected patients in the HAART era: incidence, risk, and impact of the pneumococcal vaccination; Lopez-Palomo C et al.; The objective of this study was to assess the factors implicated in an increased or decreased risk of pneumonia, with particular attention to the response to highly active antiretroviral therapy (HAART) and the effect of the polysaccharide 23-valent pneumococcal vaccination in 300 human immunodeficiency virus (HIV)-infected adults followed-up for a median of 35.6 months . Pneumococcal pneumonia occurred in 12 patients and all bacterial pneumonia (pneumonia caused by Streptococcus pneumoniae or other bacteria, as well as those with negative cultures but presumably bacterial in origin) in 40 patients . In the univariate analysis, immunodepressed patients (defined as those with less than 200 CD4+ T cell/microl), those without immunological response to HAART (defined as an increase of 25% of CD4+ T lymphocyte count), patients with previous admissions to hospital and those with cotrimoxazole or Mycobacterium avium intracellulare prophylaxis showed a higher incidence of both pneumococcal and all bacterial pneumonia . Multivariate analysis demonstrated that the presence of pneumococcal pneumonia was associated with a CD4+ lymphocyte count at the time of HIV diagnosis <200 cells/microl . The multivariate model that was more valid for prediction of all bacterial pneumonia included a CD4+ T cell count <200 cells/microl and absence of immunological response to HAART . Only in patients with a baseline CD4+ T cell count lower than 200/microl and immunological response to HAART, a near significant lower incidence of all bacterial pneumonia was observed after vaccination . Thus, these results do not support an important additional protective effect of 23-valent pneumococcal vaccine in HIV-patients with immunological response to HAART .

J Dent Res, 2004 Mar, 83(3), 266 - 70
Construction and immunogenic characterization of a fusion anti-caries DNA vaccine against PAc and glucosyltransferase I of Streptococcus mutans; Guo JH et al.; Glucosyltransferases (GTFs) and A cell-surface protein (PAc) are two important virulence factors of the cariogenic organism Streptococcus mutans . They may mediate sucrose-independent or sucrose-dependent attachment of Streptococcus mutans to tooth surfaces, respectively . Thus, inhibiting both virulence factors is predicted to provide better protection against caries than inhibiting a single factor . To develop a highly efficient vaccine against caries, we constructed a fusion DNA vaccine, pGLUA-P, by cloning the GLU region of GTF into a DNA vaccine, pCIA-P, which encodes two highly conservative regions of PAc . In this report, we provide evidence that fewer caries lesions were observed in rats following subcutaneous injection of pGLUA-P, compared with pCIA-P, near the submandibular gland . Our findings suggest that a multigenic DNA vaccine may be more caries-preventive than a single-gene DNA vaccine.

J Exp Med, 2004 Mar 1, 199(5), 717 - 23 Epub 2004 Feb 23.
FcgammaRIIb balances efficient pathogen clearance and the cytokine-mediated consequences of sepsis; Clatworthy MR et al.; The immune response to infection must be controlled to ensure it is optimal for defense while avoiding the consequences of excessive inflammation, which include fatal septic shock . Mice deficient in FcgammaRIIb, an inhibitory immunoglobulin G Fc receptor, have enhanced immune responses . Therefore, we examined whether FcgammaRIIb controls the response to Streptococcus pneumoniae . Macrophages from FcgammaRIIb-deficient mice showed increased antibody-dependent phagocytosis of pneumococci in vitro, and consistent with this infected FcgammaRIIb-deficient mice demonstrated increased bacterial clearance and survival . In contrast, previously immunized FcgammaRIIb-deficient mice challenged with large inocula showed reduced survival . This correlated with increased production of the sepsis-associated cytokines tumor necrosis factor alpha and interleukin 6 . We propose that FcgammaRIIb controls the balance between efficient pathogen clearance and the cytokine-mediated consequences of sepsis, with potential therapeutic implications.

Bioorg Med Chem, 2004 Mar 1, 12(5), 921 - 5
Hydroquinone, a control agent of agglutination and adherence of Streptococcus mutans induced by sucrose; Himejima M et al.; Hydroquinone was found to alter agglutination of Streptococcus mutans induced by sucrose . The newly formed agglutination product produced by hydroquinone does not kill this cariogenic bacterium and the formation is reversible . The agglutination altering activity of hydroquinone seems to be specific for strains of S . mutans . As a result, hydroquinone inhibits sucrose-induced adherence of S . mutans.

Epidemiol Infect, 2004 Jan, 132(1), 145 - 9
Surveillance of severe invasive group-G streptococcal infections and molecular typing of the isolates in Japan; Ikebe T et al.; The number of patients with severe invasive group-G streptococcal (Streptococcus dysgalactiae subsp . equisimilis) infections has been increasing in Japan . The emm genotypes and SmaI-digested pulsed-field gel electrophoresis DNA profiles were variable among the strains isolated, suggesting there has not been clonal expansion of a specific subpopulation of strains . However, all strains carried scpA, ska, slo and sag genes, some of which may be involved in the pathogenesis of the disease.

Bull Acad Natl Med, 2003, 187(6), 1107 - 16
{New strategies for angina case management in France}; Portier H et al.; Old French recommendations were to treat all pharyngitis cases to prevent acute rheumatic fever . 85 to 90% of cases were treated (8 to 9 millions/year), of which 3/4 unnecessary . Furthermore, penicillin V the drug of first choice was prescribed only to 5 to 10% of patients . Considering the preocupating increase of bacterial resistances and the disponibility of performane Group A Beta-Hemolytic Streptococcus Rapid Diagnostic Test (Negative Predictive Value above 95%), the new management strategy is proposed in two ways . Firstly, the free delivery of RDT to practitioners which was associated in Burgundy with a dramatic prescription decrease to 41% without benefice lost for patients . Considering these good results the French authorities decided the generalization of RDT use in 2002 and more than 15,000 practitioners have been concerned by the formations delivered in 3 months . Secondly, the short course treatment assays initiated by our group have been validated and since 2002 the AFSSAPS recommend the preferential use of compounds which obtained the authorization of use in short course with a new indication incitating to document GABHS pharyngitis by the RDT use.

Infez Med, 1996, 4(2), 74 - 8
{Epidemiologic surveillance of streptococcus pyogenes resistances to macrolides and lincosamides}; Camporese A et al.; With the changing face of modern medicine and increased use of new antimicrobial compounds against Streptococcus pyogenes, as macrolides, in recent years more strains developed new resistance to macrolides and lincosamides . This is of interest because some scientists believe that the new antibiotics policies possibly influence the rate of resistance in Streptococcus pyogenes: the pattern of resistance to macrolides is complex and involving cross or co-resistance with chemically unrelated or related agents, as lincosamides.To obtain current epidemiological data on antimicrobial resistance of Streptococcus pyogenes, we performed an year surveillance study: the rate of resistance to erythromycin was from 4% in October 1994 to 55% in December 1995, and in the same time clarithromycin was from 0% to 46% and clindamycin from 0% to 32%.

J Immunol, 2004 Mar 1, 172(5), 3132 - 8
Toll-like receptor 2 plays a role in the early inflammatory response to murine pneumococcal pneumonia but does not contribute to antibacterial defense; Knapp S et al.; Toll-like receptors (TLR) are crucial pattern recognition receptors in innate immunity . The importance of TLR2 in host defense against Gram-positive bacteria has been suggested by the fact that this receptor recognizes major Gram-positive cell wall components, such as peptidoglycan and lipoteichoic acid . To determine the role of TLR2 in pulmonary Gram-positive infection, we first established that TLR2 is indispensable for alveolar macrophage responsiveness toward Streptococcus pneumoniae . Nonetheless, TLR2 gene-deficient mice intranasally inoculated with S . pneumoniae at doses varying from nonlethal (with complete clearance of the infection) to lethal displayed only a modestly reduced inflammatory response in their lungs and an unaltered antibacterial defense when compared with normal wild-type mice . These data suggest that TLR2 plays a limited role in the innate immune response to pneumococcal pneumonia, and that additional pattern recognition receptors likely are involved in host defense against this common respiratory pathogen.

Infect Immun, 2004 Mar, 72(3), 1799 - 803
Identification of srv, a PrfA-like regulator of group A streptococcus that influences virulence; Reid SD et al.; We have identified a Crp/Fnr-like transcriptional regulator of Streptococcus pyogenes that when inactivated attenuates virulence . The gene, named srv for streptococcal regulator of virulence, encodes a 240-amino-acid protein with 53% amino acid similarity to PrfA, a transcriptional activator of virulence in Listeria monocytogenes.

Infect Immun, 2004 Mar, 72(3), 1618 - 25
Role for serine protease HtrA (DegP) of Streptococcus pyogenes in the biogenesis of virulence factors SpeB and the hemolysin streptolysin S; Lyon WR et al.; The serine protease HtrA is involved in the folding and maturation of secreted proteins, as well as in the degradation of proteins that misfold during secretion . Depletion of HtrA has been shown to affect the sensitivity of many organisms to thermal and environmental stresses, as well as being essential for virulence in many pathogens . In the present study, we compared the behaviors of several different HtrA mutants of the gram-positive pathogen Streptococcus pyogenes (group A streptococcus) . Consistent with prior reports, insertional inactivation of htrA, the gene that encodes HtrA, resulted in a mutant that grew poorly at 37 degrees C . However, an identical phenotype was observed when a similar polar insertion was placed immediately downstream of htrA in the streptococcal chromosome, suggesting that the growth defect of the insertion mutant was not a direct result of insertional inactivation of htrA . This conclusion was supported by the observation that a nonpolar deletion mutation of htrA did not produce the growth defect . However, this mutation did affect the production of several secreted virulence factors whose biogenesis requires extensive processing . For the SpeB cysteine protease, the loss of HtrA was associated with a failure to proteolytically process the zymogen to an active protease . For the streptolysin S hemolysin, a dramatic increase in hemolytic activity resulted from the depletion of HtrA . Interestingly, HtrA-deficient mutants were not attenuated in a murine model of subcutaneous infection . These data add to the growing body of information that implies an important role for HtrA in the biogenesis of secreted proteins in gram-positive bacteria.

Infect Immun, 2004 Mar, 72(3), 1587 - 93
A locus contained within a variable region of pneumococcal pathogenicity island 1 contributes to virulence in mice; Brown JS et al.; We have previously described a 27-kb pathogenicity island of Streptococcus pneumoniae, termed pneumococcal pathogenicity island 1 (PPI1), which contains iron uptake locus piaABCD, required for full virulence in mice, and a further 28 previously uncharacterized genes . We have investigated one of these, Sp1051, which encodes a protein of unknown function . Disruption of Sp1051 does not affect growth in laboratory broth, serum, or blood but impairs virulence in mouse models of infection . When S . pneumoniae capsular serotypes were analyzed by PCR and Southern hybridization, it was found that 33% did not contain Sp1051 . Analysis of other genes within PPI1 demonstrated that, compared to the serotype 4 genome published by The Institute for Genome Research (TIGR), the genomes of many strains contain deletions of a variable number of genes between Sp1046 and Sp1064, conforming to one of six different patterns . Amplification by PCR of this PPI1 variable region from a capsular serotype 17 strain and comparison of the sequence to TIGR serotype 4 strain sequence showed that Sp1051 is contained within an 11.3-kb segment of DNA flanked by 7-bp direct repeats within the serotype 4 strain which is not present in the serotype 17 strain . Further comparison of the sequences of this region between the three published S . pneumoniae genomes demonstrated that serotype 19F and strain R6 contain novel complements of genes not present in the serotype 4 strain . These data indicate that there is striking variation in gene content and structure of the 3' region of PPI1 among strains and that this region includes at least one virulence determinant . Gene variation within horizontally acquired DNA such as that of PPI1 may be one factor modulating differences in virulence among strains.

Infect Immun, 2004 Mar, 72(3), 1548 - 56
Epitope mapping of a protective monoclonal antibody against Pneumocystis carinii with shared reactivity to Streptococcus pneumoniae surface antigen PspA; Wells J et al.; Pneumocystis carinii is an opportunistic fungal pathogen that causes pneumonia in the immunocompromised host . A protective monoclonal antibody (MAb) termed 4F11 generated against mouse-derived P . carinii was shown by indirect immunofluorescence assay (IFA) to bind surface antigens of P . carinii derived from multiple host species, including humans . We have identified multiple epitopes recognized by MAb 4F11 in two recombinant mouse P . carinii antigens . The epitopes mapped have similar proline content and positive charge distribution . The consensus 8-mer epitope recognized by MAb 4F11 is K/RPA/RPK/QPA/TP . Immune sera raised against intact mouse P . carinii recognized native antigens affinity purified with MAb 4F11 and a recombinant antigen reactive with MAb 4F11 . Database searches for short, nearly exact matches to the mapped MAb 4F11 epitopes identified a bacterial surface antigen, Streptococcus pneumoniae PspA, with a similar proline-rich region . In an IFA, MAb 4F11 detected antigens on the S . pneumoniae surface, and Western blotting identified a protein in S . pneumoniae lysates consistent with the M(r) of PspA . A fragment of the S . pneumoniae PspA gene was cloned and sequenced, and the deduced amino acid sequence contained a region with strong similarity to the MAb 4F11 epitopes identified in P . carinii . The PspA recombinant polypeptide was recognized by MAb 4F11 in a Western blot . The ability of MAb 4F11 to recognize similar proline-rich epitopes may explain its ability to recognize P . carinii derived from multiple hosts and will permit testing of the epitopes recognized by this antibody in immunization against P . carinii.

Infect Immun, 2004 Mar, 72(3), 1441 - 9
Invasion of porcine brain microvascular endothelial cells by Streptococcus suis serotype 2; Vanier G et al.; Streptococcus suis is an important swine pathogen that mainly causes meningitis and occasionally causes other infections, such as endocarditis, arthritis, and pneumonia . The pathogenesis of S . suis infection has not been completely defined . However, in order to cause meningitis, S . suis has to cross the blood-brain barrier (BBB) made up of brain microvascular endothelial cells . The objective of this work was to study the interactions of S . suis serotype 2 with porcine brain microvascular endothelial cells (PBMEC) . The ability of North American and European S . suis serotype 2 strains to adhere to PBMEC and, most importantly, to invade PBMEC was demonstrated by using an antibiotic protection assay and was confirmed by electron microscopy . The polysaccharide capsule of S . suis seemed to partially interfere with the adhesion and invasion abilities of the bacterium . Our results showed that intracellular viable S . suis could be found in PBMEC up to 7 h after antibiotic treatment . Inhibition studies demonstrated that invasion of PBMEC by S . suis required actin microfilaments but not microtubular cytoskeletal elements or active bacterial RNA or protein synthesis . At high bacterial doses, suilysin-positive strains were toxic for PBMEC . The role of suilysin in cytotoxicity was confirmed by using purified suilysin, electron microscopy, and the lack of toxicity of a suilysin-negative mutant . In swine, the invasion of endothelial cells of the BBB could play an important role in the pathogenesis of the meningitis caused by S . suis.

Infect Immun, 2004 Mar, 72(3), 1341 - 8
Glyceraldehyde-3-phosphate dehydrogenase of Streptococcus oralis functions as a coadhesin for Porphyromonas gingivalis major fimbriae; Maeda K et al.; Cohesive interactions between Porphyromonas gingivalis and plaque-forming bacteria, such as Streptococcus oralis, are considered to play an important role in the colonization of P . gingivalis in periodontal sites . Although P . gingivalis fimbriae have been reported to mediate coaggregation with S . oralis, the S . oralis molecule involved has not been identified . We identified the coadhesin of S . oralis ATCC 9811 and purified it by affinity column chromatography . We found that the molecular mass of the purified protein was approximately 40 kDa . Dot blot and Western blot assays showed binding of the 40-kDa protein to P . gingivalis fimbriae . Further, turbidimetric assays showed that the coadhesin inhibited coaggregation between P . gingivalis and S . oralis in a dose-dependent manner . Analyses of the amino-terminal sequences of the protein and its lysyl endopeptidase-cleaved fragments revealed that the coadhesin was identical to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) . Next, we cloned the gene that encodes S . oralis GAPDH and found that the sequence had a high degree of homology with the sequences of GAPDHs of various bacteria, including Streptococcus gordonii and Fusobacterium nucleatum . To confirm the contribution of S . oralis GAPDH to the interaction with P . gingivalis, a recombinant GAPDH protein was generated in Escherichia coli; this protein bound to P . gingivalis fimbriae and had an inhibitory effect on coaggregation . These results suggest that S . oralis GAPDH functions as a coadhesin for P . gingivalis fimbriae . In addition, considering the high degree of homology of the GAPDHs of various bacteria, those of other plaque-forming bacteria also may contribute to the colonization of P . gingivalis.

Front Biosci, 2004 May 01, 9, 1382 - 97
Manganese-dependent protein O-phosphatases in prokaryotes and their biological functions; Shi L; During the past decade, numerous Mn2+-dependent protein serine, threonine and/or tyrosine phosphatases (O-phosphatases) from prokaryotes have been characterized . Based on their amino acid sequences, they belong to PPP, PPM or PHP superfamilies . Both the PPP and PPM families of protein phosphatases are metalloenzymes which active centers contain two metal ions that function as cofactors . Results from sequence analysis also suggest that PHP family protein phosphatase is a metalloenzyme . The identified functions for PPP family protein phosphatases from different prokaryotic organisms include regulation of stress-response, nitrogen fixation and vegetative growth . At least one phosphatase, PrpB from Escherichia coli, is also implicated in bacterial pathogenesis . Prokaryotic PPM family protein phosphatases are involved in controlling spore formation, stress-response, cell density during stationary phase, carbon and nitrogen assimilation, vegetative growth, development of fruiting bodies and cell segregation . The function of CpsB, a PHP family protein tyrosine phosphatase from Streptococcus pneumonia, is to regulate biosynthesis of capsular polysaccharide, an important virulence determinant . Thus, this group of functionally diverse protein phosphatases plays an important role in prokaryotes . Discovery of Mn2+-dependent prokaryotic protein O-phosphatases and their functions also contributes to new insight into Mn2+ homeostasis and many roles played by Mn2+ and protein O-phosphorylation in prokaryotic cells.

J Endod, 2004 Feb, 30(2), 92 - 4
Effectiveness of sodium hypochlorite in preventing inoculation of periapical tissues with contaminated patency files; Izu KH et al.; The aim of this study was to analyze the effectiveness of 5.25% sodium hypochlorite (NaOCI) in preventing inoculation of periapical tissues with contaminated patency files . Twenty-eight extracted human permanent teeth with single canals were used in the study . Group I teeth were filled with NaOCl, and #15 stainless steel files contaminated with Streptococcus sanguis (ATCC #10556) were allowed to pass through the NaOCI into the culture medium . The teeth in group II were also filled with NaOCl, but the contaminated files used in group II canals were immersed in NaOCl for 10 s prior to being placed into the canals and cultured . The negative control group used sterile files (0% growth), the first positive control group used contaminated patency files in teeth with empty canals (100% growth), and the second positive control group placed contaminated files into broth next to teeth filled with NaOCl (to evaluate potential chlorine leakage; 100% growth) . The experimental results showed no positive growth of S . sanguis for groups I and II, indicating that the NaOCl present in the canal after irrigation was sufficient to kill the test organism.

Acta Otolaryngol, 2004 Jan, 124(1), 23 - 5
Bacteriology of mastoid subperiosteal abscess in children; Migirov L et al.; OBJECTIVE: Subperiosteal abscess (SA) is the most frequent complication of acute mastoiditis (AM) . Of pathogens cultured from the external auditory canal or middle ear during myringotomy, 15% may be different from microorganisms isolated from the SA . We suggest, therefore, that only cultures obtained from the abscess cavity can truly reflect the bacteriology of this complication of AM . The purpose of our study was to analyze the infectious agents which cause SA and mastoid cortex erosion in children . MATERIAL AND METHODS: The medical records of 35 children who underwent mastoidectomy for SA between May 1984 and April 2002 were evaluated . RESULTS: Mastoid cortex erosion was found at surgery in 72.7% of abscesses Purulent discharge was obtained from the SA cavity in 28 cases . The commonest pathogens isolated in these cases, as well as in 18 cases of mastoid cortex erosion, were Staphylococcus aureus and Streptococcus pyogenes, followed by Streptococcus pneumoniae . Hemophilus influenzae, Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae . Sterile culture was found in 25% of cases . CONCLUSIONS: Mastoid SA is a unilateral disease that can recur . Early administration of anti-Staphylococcus medications should be considered for patients with SA as a complication of AM.

J Infect Dis, 2004 Mar 1, 189(5), 797 - 804 Epub 2004 Feb 18.
Low antibody levels against cell wall-attached proteins of Streptococcus pyogenes predispose for severe invasive disease; Akesson P et al.; Acute-phase serum samples from 70 patients with group A streptococcal (GAS) invasive disease were analyzed for IgG antibodies against 6 recently characterized GAS virulence factors (SclA, SclB, GRAB, MtsA, EndoS, and IdeS) and SpeB . Antibody levels against the cell wall-attached GAS antigens SclA, SclB, and GRAB were significantly lower in patients with severe invasive disease (streptococcal toxic shock syndrome {STSS} and/or necrotizing fasciitis {NF}; n=35), compared with levels in patients with nonsevere GAS bacteremia (n=35) . Among patients with severe invasive disease, significantly lower antibody levels against GRAB were found in patients with STSS (n=10) than in patients with NF (n=17) . Antibody levels against SpeB in patients with severe bacteremia were similar to those in patients with nonsevere bacteremia, and levels in patients with STSS were similar to those in patients with NF . The data indicate that immunity to cell wall-attached proteins may play a role in the protection against severe invasive disease and that antibodies against GRAB may be of importance in the pathogenesis of STSS.

J Infect Dis, 2004 Mar 1, 189(5), 785 - 96 Epub 2004 Feb 16.
Effect of clonal and serotype-specific properties on the invasive capacity of Streptococcus pneumoniae; Sandgren A et al.; The present study compares the molecular epidemiology of Streptococcus pneumoniae causing invasive disease and carriage, respectively, in one geographic area (Stockholm, Sweden) during a specific point in time (the year 1997) . A total of 273 invasive isolates (257 from adults and 16 from children) obtained from the 2 major hospitals in Stockholm, as well as 246 nasopharyngeal isolates recovered from children attending 16 day-care centers in the Stockholm area, were analyzed by serotyping, molecular typing (by pulsed-field gel electrophoresis and multilocus sequence typing), and antibiotic susceptibility testing . Of the 34 different serotypes plus nontypeable strains identified in the present study, 12 were never found among the 246 colonizing isolates, whereas only 3 were never found among the 273 invasive isolates . The isolates formed 2 major classes: 1 class that was found mainly among invasive isolates (type 1, 4, 7F, and 9V isolates) and was clonally highly related and 1 class that caused invasive disease but was also common in carriage (including type 6A, 6B, 14, and 19F isolates) and was genetically more diverse . Clones were found that belonged to the same serotype but had different abilities to cause invasive disease . Also, isolates belonging to the same clone were found, although they had different capsules because of serotype switch, and were found to have the same disease potential . Hence, properties associated with a particular clonal type, in addition to capsular serotype, are likely to be important for the potential of pneumococci to cause invasive disease.

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