Curr Opin Investig Drugs, 2001 Jun, 2(6), 766 - 72 ABT-773 (Abbott Laboratories); Lawrence LE; ABT-773 is a macrolide antibacterial agent under development by Abbott Laboratories and Taisho Pharmaceutical Co Ltd for the potential treatment of bacterial infection {266579} . As of February 2001, ABT-773 had entered phase III trials in the US {398274} . Japanese phase II trials were expected to commence in June 2000 and a phase II trial is being designed for respiratory infections, with Abbott expecting filing in March 2002 {360455} . The bioavailability of ABT-773 in humans is unaffected by food {383228} and in a phase I, randomized, double-blind trial in healthy males only mild adverse effects, usually affecting the gastrointestinal system, were observed {383208} . Under an agreement, Abbott and Taisho are conducting joint research to discover new compounds; Abbott will have worldwide marketing, manufacturing and supply rights (except in Japan), and Taisho will receive royalties on Abbott's sales in consideration of granted rights . In Japan, the companies will co-market any resulting compounds {266579} . ABT-773 demonstrated good activity in vitro and in vivo against Streptococcus pneumoniae and Staphylococcus aureus {383229}, {383231}, and was highly potent even against macrolide-resistant {382149}, {382150} and invasive {383782} S pneumoniae. Curr Opin Investig Drugs, 2001 Jun, 2(6), 745 - 51 Antibacterial agents (oxazolidinones, quinolones, macrolides and new agents): patent highlights June to December 2000; Phillips OA et al.; Several patent disclosures were made on oxazolidinone, quinolone, macrolide and new antimicrobial agents between June and December 2000; 26 of these patents are discussed in this review . The exciting report on new oxazolidinone derivatives with potent activity against fastidious Gram-negative organisms is highlighted . Most of the new quinolones are structurally dissimilar to the traditional fluoroquinolones and demonstrate activity against Helicobacter pylori (MIC=0.013 microg/ml) . New 14-membered macrolides with broad-spectrum activity including against Mycobacterium avium are also presented . A novel peptidic antibiotic with potent antimicrobial activity against Streptococcus pneumoniae (MIC<0.0005 microg/ml) is also highlighted. Appl Environ Microbiol, 2001 Oct, 67(10), 4828 - 33 Streptococcus suis serotypes characterized by analysis of chaperonin 60 gene sequences; Brousseau R et al.; Streptococcus suis is an important pathogen of swine which occasionally infects humans as well . There are 35 serotypes known for this organism, and it would be desirable to develop rapid methods methods to identify and differentiate the strains of this species . To that effect, partial chaperonin 60 gene sequences were determined for the 35 serotype reference strains of S . suis . Analysis of a pairwise distance matrix showed that the distances ranged from 0 to 0.275 when values were calculated by the maximum-likelihood method . For five of the strains the distances from serotype 1 were greater than 0.1, and for two of these strains the distances were were more than 0.25, suggesting that they belong to a different species . Most of the nucleotide differences were silent; alignment of protein sequences showed that there were only 11 distinct sequences for the 35 strains under study . The chaperonin 60 gene phylogenetic tree was similar to the previously published tree based on 16S rRNA sequences, and it was also observed that strains with identical chaperonin 60 gene sequences tended to have identical 16S rRNA sequences . The chaperonin 60 gene sequences provided a higher level of discrimination between serotypes than the 16S RNA sequences provided and could form the basis for a diagnostic protocol. Arch Pathol Lab Med, 2001 Oct, 125(10), 1285 - 9 Method preferences and test accuracy of antimicrobial susceptibility testing: updates from the College of Amercian Pathologists Microbiology Surveys Program; Jones RN; College of American Pathologists Microbiology Resource Committe; OBJECTIVE: To summarize the antimicrobial susceptibility testing results from the College of American Pathologists (CAP) Microbiology Surveys Program for 2000 . Specifically, the frequency of tests used and the quantitative and qualitative (susceptibility category) accuracy were assessed . DESIGN: The CAP Microbiology Surveys challenged subscribers in 2000 with 3 well-characterized organisms for antimicrobial susceptibility testing in pure culture . Each laboratory was to use the test method and reporting procedures routinely applied to patient samples . The strains were National Committee for Clinical Laboratory Standards (NCCLS) quality control organisms with precisely defined antimicrobial susceptibility patterns and reproducibility . Results reported by participants (2685-2979/sample) were graded for categorical accuracy and quantitative performance by comparing reported minimal inhibitory concentrations (microg/mL) or zone diameters (mm) against quality control ranges published by the NCCLS . The appropriateness of reported drugs was determined in the context of the type and anatomic location of the infection . RESULTS: The tests most often used varied by the species of the organism and growth characteristics of the isolated strains . Nonfastidious, rapid-growing Surveys unknowns (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853) were most often tested with commercial systems (MicroScan, 42.0%-42.4%; Vitek, 41.5%-43.0%) or with the standardized disk diffusion method (12.8%-13.9%) . In contrast, fastidious species, such as Streptococcus pneumoniae (ATCC 49619), were predominantly tested by Etest (40.3%), followed by disk diffusion (27.6%) and MicroScan (23.2%) . Categorical accuracy was essentially equal between dilution (98.9%) and diffusion (99.0%) methods . Among the minimal inhibitory concentration methods used to test penicillin against S pneumoniae, Etest method quantitative accuracy (96.3%) was greater than that of MicroScan (92.4%) . Quantitative accuracy was greatest for dilution minimal inhibitory concentration methods, with more than 90% of results within NCCLS quality control ranges for nearly all reported antimicrobials . Reevaluations of quality control ranges may be needed for 4 to 7 agents, depending on method . Reporting errors were also detected in 2 areas: (1) reporting results for drugs not active at the site of infection and (2) reporting results for drugs tested with suboptimal methods without published NCCLS interpretive criteria . CONCLUSIONS: Antimicrobial susceptibility testing methods used in US laboratories were dominated by commercial products with relatively high accuracy (qualitative and quantitative) . As available methods have become better suited to both fastidious and rapid-growing species, reporting errors have assumed a higher level of concern to the CAP Surveys in an effort to minimize prescription errors. Immunol Invest, 2001 Aug, 30(3), 191 - 207 A multi-laboratory evaluation of an enzyme-linked immunoassay quantitating human antibodies to Streptococcus pneumoniae polysaccharides; Quataert S et al.; An enzyme-linked immunoassay (EIA) is described and evaluated which quantitates human antibodies to serotype specific S . pneumoniae polysaccharide (PnPs) in human sera . Based on the observations previously described by Koskela (1), native PnPs are used as coating antigens and sera are absorbed with a soluble pneumococcal absorbant material containing C-polysaccharide (CPs) to ensure measurement of serotype specific anti-PnPs antibodies . The robustness of this method was evaluated by ten laboratories using the same reagents, protocol, and five human serum samples . Reproducible antibody values were obtained for IgM, IgG, and IgA antibodies to five different PnPs serotypes, 3, 6B, 14, 19F, and 23F . The overall mean percent coefficients of variation in this interlaboratory study for all five selotype specific anti-PnPs determinations with the five coded sera were 30% for IgG, 3/% for IgM, and 36% for IgA . This assay can be standardized for quantitation of serotype specific anti-PnPs antibodies, allowing comparison of antibody values in vaccine trials evaluating pneumococcal vaccines. Mil Med, 2001 Sep, 166(9), 759 - 63 Prospective study of respiratory infections at the U.S . Naval Academy; Gray GC et al.; Midshipmen at the U.S . Naval Academy have recently suffered epidemics of upper respiratory tract infections . Seeking to determine cause, in June 1998 we enrolled 1,243 (99.5%) of 1,249 new midshipmen (plebes) and followed them during their first 11 months of training . Eighty-five plebes sought medical attention for acute respiratory disease . Using culture, serologic studies, and polymerase chain reaction, considerable evidence for respiratory pathogen infection was found among the ill subjects: Chlamydia pneumoniae in 41 (52.6%), Mycoplasma pneumoniae in 19 (25.3%), influenza in 11 (14.2%), Streptococcus pneumoniae in 6 (7.3%), and adenovirus in 1 (1.2%) . Additionally, 873 (81%) the 1,077 plebes who completed an end-of-year questionnaire complained of having one or more respiratory symptoms (> 12 hours) during their first year of school . Of these, 132 (15%) reported that the symptoms significantly affected their performance . Study results suggest that respiratory infections were frequent, had a significant adverse impact on training, and were often attributable to bacterial pathogens. Am J Obstet Gynecol, 2001 Sep, 185(3), 586 - 92 An in vitro study of antibacterial properties of the cervical mucus plug in pregnancy; Hein M et al.; OBJECTIVE: To evaluate whether cervical mucus plugs are antibacterial in vitro . STUDY DESIGN: Cervical mucus plugs from 56 healthy women in labor were studied by 2 different antimicrobial assays: (1) analysis of the inhibition by the cervical mucus plug of several gram-positive and gram-negative bacteria by overlaying the cervical mucus plug onto an agar plate with imbedded bacteria, and (2) determination of the antibacterial property of the cervical mucus plug material by radial diffusion assay with group B Streptococcus and Escherichia coli . RESULTS: In the agar overlay assay, there was complete inhibition of clinical isolates of Staphylococcus saprophyticus, E coli, and Pseudomonas aeruginosa and patient-variable partial-to-complete inhibition of Enterococcus faecium, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus agalactiae . In the radial diffusion assay, cervical mucus plugs had activity toward group B Streptococcus equivalent to 0.075 microg/mL of gentamicin and toward E coli equivalent to 0.5 microg/mL of gentamicin . CONCLUSION: A low-molecular substance with antibacterial activity in the cervical mucus plug may protect the fetus against ascending infections. Dent Mater, 2001 Nov, 17(6), 485 - 91 Inhibitory effects of resin composite containing bactericide-immobilized filler on plaque accumulation; Ebi N et al.; OBJECTIVE: Previously, we have reported that incorporation of the antibacterial monomer 12-methacryloyloxydodecylpyridinium bromide (MDPB) was effective in immobilizing bactericide in the resin matrix, and an antibacterial composite without release of the agent could be achieved . In this study, an attempt was made to increase the density of bactericide immobilized in composite, and the inhibitory effects of this modified antibacterial composite on plaque accumulation were determined, focusing on the reliability of the effects and the mechanisms to affect the plaque formation . METHODS: An experimental composite containing immobilized bactericide at 2.83% was prepared by the incorporation of MDPB into a prepolymerized resin filler of control composite, and elution of antibacterial components and inhibition of in vitro plaque accumulation by Streptococcus mutans were determined . The inhibitory effects of the experimental composite on the attachment, glucan synthesis and growth of S . mutans on the surface were also examined in addition to the comparison of surface roughness and hydrophobicity with controls . The results were analyzed using the Student's t-test . RESULTS: The experimental composite had reproducible inhibitory effects against plaque accumulation compared with control (p<0.05), although it showed no elution of unpolymerized MDPB . The plaque-inhibitory effect of the experimental composite was found to depend upon the ability to inhibit the attachment, glucan synthesis, and growth of bacteria on its surface as no significant differences in the surface characteristics were obtained between control and experimental composites (p>0.05) . SIGNIFICANCE: It was indicated that the experimental composite containing bactericide-immobilized filler has the possibility to be used clinically with an effective anti-plaque property. J Bacteriol, 2001 Oct, 183(20), 5964 - 73 uvrA is an acid-inducible gene involved in the adaptive response to low pH in Streptococcus mutans; Hanna MN et al.; The pH-inducible acid tolerance response (ATR) is believed to play a major role in acid adaptation and virulence of Streptococcus mutans . To study this phenomenon in S . mutans JH1005, differential display PCR was used to identify and clone 13 cDNA products that had increased expression in response to pH 5.0 compared to that of pH 7.5-grown cells . One of these products, confirmed to be pH inducible by RNA dot blot and reverse transcription-PCR analyses, had 67% identity to a uvrA-UV repair excinuclease gene in Bacillus subtilis . Further sequence analysis of the uvrA homologue using the S . mutans genome database revealed that the complete gene was encoded in an open reading frame (ORF) of 2,829 bp (944 amino acids; 104.67 kDa) . Immediately 3' of uvrA was an ORF encoding a putative aminopeptidase gene (pepP) . uvrA knockouts were constructed in S . mutans strains JH1005, NG8, and UA159 using allelic-exchange mutagenesis, replacing the entire gene with an erythromycin resistance cassette . As with uvrA mutants in other bacteria, the S . mutans uvrA mutants were extremely sensitive to UV irradiation . The uvrA mutant of S . mutans JH1005 was also more sensitive than the wild type to growth at pH 5.0, showing a 15% reduction in growth rate and a 14% reduction in final resting culture density . Acid-adapted S . mutans JH1005 uvrA mutants were shown to be more resistant to UV irradiation than was the parent but were unable to survive exposure to a killing pH of 3.0 . Moreover, agarose gel electrophoretic analysis of chromosomal DNA isolated from uvrA-deficient cells exposed to low pH demonstrated more DNA damage than that for the wild-type strain . Here we suggest that uvrA and the nucleotide excision repair pathway are involved in the repair of acid-induced DNA damage and are associated with successful adaptation of S . mutans to low pH. Arch Cardiol Mex, 2001 Apr-Jun, 71(2), 127 - 35 {Rheumatic fever in the 5-year period of 1994-1999 at 2 hospitals in San Luis Potosi and Mexico D.F.}; Soto Lopez ME et al.; OBJECTIVE: To assess the incidence of acute Rheumatic Fever (ARF) . PATIENTS AND METHODS: A retrospective, descriptive, observational study on the first attack and recurrence was performed in a general hospital and a reference center . RESULTS: By Jones criteria: 67 cases, 39 women and 28 men; 58% first attack, 42% recurrence . Higher incidence during spring-winter . The most common major criteria were: carditis, polyarthritis . The most common minor criteria were: fever, arthralgias and acute phase reaction markers . No differences between hospitals were noted . Evidence of contact with streptococcus was found . Mitral, aortic and tricuspid valves were commonly affected . Incidence in the age group > 5 < 20 was 7/1000 . DISCUSSION: Incidence of ARF has decreased, but has not been eradicated . It occurs in developing countries, where it remains an issue of public health . Failures in clinical suspicion, prophylaxis, and adherence to treatment influence this situation . Education for health, early diagnosis, and primary and secondary prophylaxis should be reinforced. Clin Infect Dis, 2001 Oct 15, 33(8), 1324 - 8 Epub 2001 Sep 17. Time to positivity of blood cultures for children with Streptococcus pneumoniae bacteremia; Neuman MI et al.; We report on a 3-year (1 January 1996 through 31 December 1999) retrospective chart review of children with Streptococcus pneumoniae bacteremia to identify the time to identification of growth of S . pneumoniae in blood culture and to attempt to identify clinical predictors of early versus late growth of S . pneumoniae in culture . The time to detection of S . pneumoniae in blood culture for immunocompetent patients ranged from 4.4 to 25.9 hours (h), with a mean of 11.5 h (standard deviation, 2.8) . There was no difference in the time to detection for immunocompromised versus immunocompetent patients . The 10th and 90th deciles for time to detection among immunocompetent patients were 9.2 and 14.0 h, respectively . There were no differences in white blood cell count, absolute neutrophil count, or height of fever between the lowest and highest decile groups . Ninety percent of blood cultures yielding S . pneumoniae are noted positive within 14 h, and no clinical or laboratory parameters accurately predicted early versus late growth of S . pneumoniae in blood culture. Semin Respir Infect, 2001 Sep, 16(3), 186 - 95 Drug-resistant Streptococcus pneumoniae infections: clinical importance, drug treatment, and prevention; Kellner JD; Drug-resistant Streptococcus pneumoniae (DRSP) have complicated the management of pneumococcal infections throughout the world in recent years . Important risk factors for the development of a DRSP infection include recent antibiotic use, young age, immunosuppression, daycare center attendance, and recent hospitalizations . Although intermediate resistance to beta-lactam antibodies does not appear to have an impact on the mortality of S . pneumoniae infections, evidence is accumulating to suggest that more highly resistant isolates may increase mortality . Clinical and bacteriologic failures are more common in DRSP meningitis and otitis media . To select appropriate therapy, one must consider whether a patient has risk factors for resistance, the site and severity of the infection, and antibiotic susceptibility data . Reducing the impact of DRSP may be achieved through reducing antibiotic use in communities and increased understanding of other factors that contribute to the development and transmission of resistance . The most important way to reduce all S . pneumoniae infections is to increase the use of existing polysaccharide vaccines and to begin to use new polysaccharide-protein conjugate vaccines in young children . Semin Respir Infect, 2001 Sep, 16(3), 177 - 85 Antimicrobial resistance with Streptococcus pneumoniae: much ado about nothing? Doern GV. During the past decade in the United States, Streptococcus pneumoniae has changed dramatically in the context of antimicrobial resistance . Resistance to multiple different antibiotic classes including beta-lactams (penicillins, cephalosporins, and beta-lactamase inhibitor combinations), macrolides, clindamycin, the tetracyclines, chloramphenicol, and trimethoprim-sulfamethoxazole (TMP/SMX) has emerged at high rates with this important respiratory tract pathogen . There is no question that the in vitro activity of these antimicrobial agents is substantially lower for many strains of S . pneumoniae than it was even a few years ago . The larger question is, however, what does this decrease in activity mean from a clinical perspective? Stated another way, does resistance defined according to current standards in the laboratory, translate into diminished effectiveness when these agents are used to treat patients with pneumococcal infections? It is this question that serves as the principal basis for this review . Med Clin (Barc), 2001 Sep 15, 117(7), 241 - 5 {Pneumococcal bacteremia in patients aged over 65 years . A study of 161 cases}; Vaqueiro Subirats M et al.; BACKGROUND: Here we present the results from a prospective analysis of pneumococcal bacteremia in patients older than 65 years, highlighting its differences with regard to patients aged from 15 to 64 years . PATIENTS AND METHOD: We performed a prospective follow-up study (1988-1999) of patients older than 14 years whohad blood cultures positive for Streptococcus pneumoniae(S . pneumoniae) . S . pneumoniae was identified using standard techniques . The antimicrobial sensitivity was analysed using the broth midrodilution technique and the serotype was studied in a reference laboratory . Statistical analyses were performed by means of the SPSS program, version 9.0 . RESULTS: 161 out of 321 bacteremias occurred in 154 patients older than 65 years (86 males) . Most frequent underlying diseases were chronic obstructive pulmonary disease (COPD), diabetes and neoplasia . Most patients had pneumonia, 29.7% with ilfiltrates involving at least two lung lobes . 9.4% of bacteremias were nosocomial . Among patients older than 65 years, 32.5% of strains were resistant to penicillin, compared to 21.7% in patients younger than 65 years(p = 0.034) . Mortality in patients over 65 years was higher than in younger patients (25.3% vs 11.5%; p = 0.002) and mortality predictive factors in a multivariate analysis were age, nosocomial bacteremia and multi-lobe involvement (in patients with pneumonia) . CONCLUSIONS: There is a high incidence of pneumococcal bacteremia in patients over 65 years of age . These patients have a higher rate of resistance to penicillin and a higher mortality rate than younger patients.Mortality predictive factors are age, nosocomial bacteremia and multi-lobe involvement. Int Immunopharmacol, 2001 Sep, 1(9-10), 1789 - 95 Severe impairment of anti-cancer effect of lipoteichoic acid-related molecule isolated from a penicillin-killed Streptococcus pyogenes in toll-like receptor 4-deficient mice; Okamoto M et al.; A lipoteichoic acid-related molecule (OK-PSA) isolated from OK-432, a penicillin-killed Streptococcus pyogenes, is a potent inducer of Th1 cytokines, and elicits anti-cancer effect in tumor-bearing mice . Toll-like receptor (TLR) 4 is a member of the recently identified toll-like receptor family of proteins that has been implicated in lipopolysaccharide-induced cell signaling . In the present study, we have examined the role of TLR4 for OK-PSA-induced Th1-cytokine production and anti-tumor effect by using C3H/HeJ mice in which TLR4 function is impaired . Although OK-PSA strikingly induced Th1 cytokines {interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-12 and IL-18} in the splenocytes derived from control animals (C3H/HeN), OK-PSA did not induce the cytokines in the splenocytes from C3H/HeJ . Furthermore, C3H/HeJ-derived splenocytes acquired the responsiveness to OK-PSA stimulation by overexpression of TLR4 gene . Finally, OK-PSA administration significantly inhibited the tumor growth and lung metastasis of syngeneic squamous cell carcinoma cells in C3H/HeN; however, no effect of OK-PSA was observed in C3H/HeJ . These findings strongly suggest that TLR4 signaling is involved in regulating OK-PSA-induced anti-cancer immunity. Epidemiol Infect, 2001 Aug, 127(1), 49 - 55 Prevalence of carriage of antimicrobial resistant strains of Streptococcus pneumoniae in primary school children in Hong Kong; Boost MV et al.; A cross-sectional survey was conducted to determine prevalence and assess risk factors for carriage of antibiotic resistant strains of Streptococcus pneumoniae in healthy school children in Hong Kong . Throat swabs were collected from 1455 subjects and written questionnaires providing demographic data and medical history were completed by parents . The overall carriage rate of Streptococcus pneumoniae was 3.5%, of which 49% were penicillin resistant . High levels of resistance to tetracycline (73%), erythromycin (52%), trimethoprim (66%) and ciprofloxacin (57%) were observed . Carriage was associated with presence of a younger sibling (OR = 1.79) and use of antibiotics (OR = 2.31) . High use of day care and small size of housing units did not result in a high rate of carriage . The low rate of carriage may be linked to high use of antibiotics, geographical factors or ethnicity . High rates of antibiotic resistance reflect heavy use of antibiotics by general practitioners. Eur J Clin Microbiol Infect Dis, 2001 Jul, 20(7), 494 - 7 Relative potency of telithromycin, azithromycin and erythromycin against recent clinical isolates of gram-positive cocci; Barry AL et al.; A ketolide (telithromycin), an azalide (azithromycin) and a macrolide (erythromycin) were tested against 2,733 isolates of gram-positive cocci gathered from 11 different medical centers . Telithromycin was active against erythromycin-resistant staphylococci that were susceptible to clindamycin but was not active against those that were resistant to clindamycin . More than 99% of all Streptococcus pneumoniae and Streptococcus pyogenes isolates were susceptible to 1 microg/ml of telithromycin including erythromycin- and azithromycin-resistant strains . Telithromycin was not only more potent than azithromycin against macrolide-susceptible strains, it was also active against most macrolide-resistant strains . Although the prevalence of macrolide-resistant pneumococci increased from 19% to 27% between 1997 and 1999, macrolide resistance among other gram-positive cocci did not change substantially in that 2-year period. Eur J Clin Microbiol Infect Dis, 2001 Jul, 20(7), 490 - 3 Reduced release of DNA from streptococcus pneumoniae after treatment with rifampin in comparison to spontaneous growth and ceftriaxone treatment; Gerber J et al.; In order to study the release of DNA from Streptococcus pneumoniae in vitro during spontaneous growth and treatment with ceftriaxone or rifampin, a semiquantitative polymerase chain reaction was used . During spontaneous growth, high concentrations of bacterial DNA were released . Exposure to 10 microg/ml of ceftriaxone decreased the DNA release, in median, by 19 times (P=0.03 vs . spontaneous growth) . Treatment with 10 microg/ml of rifampin led to a reduction of DNA release, in median, by a factor of 49 (P=0.03 vs . ceftriaxone; six experiments performed on different days). Chemotherapy, 2001 Sep-Oct, 47(5), 354 - 8 In vitro activity of novel fluoroquinolones against Streptococcus pneumoniae isolated from children with acute otitis media; Yagupsky P et al.; BACKGROUND: In recent years, novel fluoroquinolones with improved activity against gram-positive organisms have been introduced into clinical practice . These drugs may be of potential benefit for the treatment of pneumococcal otitis media, including infections caused by organisms resistant to conventional drugs . METHODS: In vitro activity of 6 fluoroquinolones against 77 pneumococcal isolates from middle-ear fluid was determined by the E test . RESULTS: Resistance to penicillin, co-trimoxazole, erythromycin, clindamycin, and tetracycline was present in 59 (76.6%), 47 (61.0%), 19 (24.7%), 11 (14.3%), and 17 (22.1%) isolates, respectively . Fluoroquinolone MIC(50) and MIC(90) (in microg/ml) were as follows: ciprofloxacin: 1.0 and 3.0, levofloxacin: 0.75 and 1.0, sparfloxacin: 0.25 and 0.38, grepafloxacin: 0.25 and 0.38, trovafloxacin: 0.094 and 0.125, and moxifloxacin: 0.19 and 0.25, respectively . CONCLUSIONS: Novel fluoroquinolones and especially trovafloxacin and moxifloxacin appear to be of potential value for the treatment of acute otitis media caused by pneumococci resistant to traditional antibiotics . Jpn J Antibiot, 2001 Jul, 54(7), 365 - 71 {In vitro and in vivo activities of panipenem against penicillin-resistant Streptococcus pneumoniae}; Fukuoka T et al.; Efficacy of panipenem/betamipron (PAPM/BP) against experimental pneumonia caused by penicillin-resistant Streptococcus pneumoniae (PRSP: MIC of benzylpenicillin, > or = 1.56 micrograms/ml) in mice was compared with those of imipenem/cilastatin (IPM/CS), meropenem (MEPM), cefozopran (CZOP), ceftriaxone (CTRX), ampicillin (ABPC), and vancomycin (VCM) . The infection was induced by inoculating a PRSP clinical isolate, 9601 (serotype 6) or 10,693 (serotype 19), into ddY male mice intranasally . Drugs were administered subcutaneously at doses of 0.4, 2, and 10 mg/kg, 18, 26, 42, and 50 hours post-infection . Viable cell counts in the lungs were determined 66 hours post-infection . PAPM/BP showed the greatest efficacy against the infections among tested drugs . MICs of PAPM against PRSP 9601 and 10,693 were both 0.125 microgram/ml, which were superior to those of IPM (0.25 and 0.5 microgram/ml, respectively), MEPM (0.5 and 1 microgram/ml, respectively), CZOP (2 and 1 microgram/ml, respectively), CTRX (both 1 microgram/ml), ABPC (both 4 micrograms/ml), and VCM (0.5 and 0.25 microgram/ml, respectively) . These results suggest that the potent in vivo activity of PAPM/BP reflects the potent in vitro activity of PAPM . MICs of PAPM, IPM, MEPM, and CZOP against clinical isolates, penicillin-susceptible S . pneumoniae (PSSP: MIC of benzylpenicillin, < or = 0.05 microgram/ml), penicillin-intermediate S . pneumoniae (PISP: MIC of benzylpenicillin, 0.1-0.78 microgram/ml), and PRSP, were tested by an agar dilution method . MIC90s of the drugs against the PSSP, PISP, and PRSP were as follows: PAPM, 0.012, 0.05, and 0.39 microgram/ml; IPM, < or = 0.006, 0.1, and 0.78 microgram/ml; MEPM, 0.05, 0.39, and 1.56 micrograms/ml; and CZOP, 0.2, 0.78, and 6.25 micrograms/ml, respectively . Thus, PAPM showed the most potent activity among tested drugs against clinical isolates of PISP and PRSP. Antimicrob Agents Chemother, 2001 Oct, 45(10), 2955 - 7 Streptococcus pneumoniae isolates with reduced susceptibility to ciprofloxacin in Spain: clonal diversity and appearance of ciprofloxacin-resistant epidemic clones; Alou L et al.; Analysis of the pulsed-field gel electrophoretic profiles of 82 pneumococcal isolates with reduced susceptibility to ciprofloxacin (RSC) and of 90 co-occurring susceptible isolates indicates a considerable genetic diversity among isolates with RCS and points to a close relation between the two groups . This finding suggests that pneumococci with RCS emerge through independent mutational events. Antimicrob Agents Chemother, 2001 Oct, 45(10), 2916 - 21 Pharmacodynamics of gemifloxacin against Streptococcus pneumoniae in an in vitro pharmacokinetic model of infection; MacGowan AP et al.; The pharmacodynamics of gemifloxacin against Streptococcus pneumoniae were investigated in a dilutional pharmacodynamic model of infection . Dose fractionation was used to simulate concentrations of gemifloxacin in human serum associated with 640 mg every 48 h (one dose), 320 mg every 24 h (two doses), and 160 mg every 12 h (four doses) . Five strains of S . pneumoniae for which MICs were 0.016, 0.06, 0.1, 0.16, and 0.24 mg/liter were used to assess the antibacterial effect of gemifloxacin . An inoculum of 10(7) to 10(8) CFU/ml was used, and each experiment was performed at least in triplicate . The pharmacodynamic parameters (area under the concentration-time curve {AUC}/MIC, maximum concentration of drug in serum {C(max)}/MIC, and the time that the serum drug concentration remains higher than the MIC {T > MIC}) were related to antibacterial effect as measured by the area under the bacterial-kill curve from 0 to 48 h (AUBKC(48)) using an inhibitory sigmoid E(max) model . Weighted least-squares regression was used to predict the effect of the pharmacodynamic parameters on AUBKC(48), and Cox proportional-hazards regression was used to predict the effect of the three pharmacodynamic parameters on the time needed to kill 99.9% of the starting inoculum (T99.9) . There was a clear relationship between strain susceptibility and clearance from the model . The simulations (160 mg every 12 h) were associated with slower initial clearance than were the other simulations; in contrast, bacterial regrowth occurred with the 640-mg simulation when MICs were > or =0.1 mg/liter . The percentage coefficient of variance was 19% for AUBKC(48), and the inhibitory sigmoid E(max) model best fit the relationship between AUBKC(48) and AUC/MIC . C(max)/MIC and T > MIC fit less well . The maximum response occurred at an AUC/MIC of >300 to 400 . In weighted least-squares regression analysis, there was no evidence that C(max)/MIC was predictive of AUBKC(48), but both AUC/MIC and T > MIC were . A repeat analysis using only data for which the T > MIC was >75% and for which hence regrowth was minimized indicated that AUC/MIC alone was predictive of AUBKC(48) . Initial univariate analysis indicated that all three pharmacodynamic parameters were predictive of T99.9, but in the multivariate model only C(max)/MIC reached significance . These data indicate that gemifloxacin is an effective antipneumococcal agent and that AUC/MIC is the best predictor of antibacterial effect as measured by AUBKC(48) . However, C(max)/MIC is the best predictor of speed of kill, as measured by T99.9 . T > MIC also has a role in determining AUBKC(48), especially when the dose spacing is considerable . Once-daily dosing seems most suitable for gemifloxacin. Antimicrob Agents Chemother, 2001 Oct, 45(10), 2865 - 70 Selection and genetic characterization of Streptococcus pneumoniae mutants resistant to the des-F(6) quinolone BMS-284756; Hartman-Neumann S et al.; Existing quinolones are known to target the type II topoisomerases in bacteria . In order to determine which of these targets are of key importance in Streptococcus pneumoniae treated with BMS-284756 (T-3811ME), a novel des-F(6) quinolone, resistant mutants were selected in several steps of increasing resistance by plating pneumococci on a series of blood agar plates containing serial twofold-increasing concentrations of drug . After incubation, colonies that arose were selected and passaged twice on antibiotic-containing media at the selection level . Mutants generally showed increases in resistance of four- to eightfold over the prior level of susceptibility . Mutants in the next-higher level of resistance were selected from the previous round of resistant mutants . Subsequently, chromosomal DNA was prepared from parental (R6) pneumococci and from at least three clones from each of four levels of increasing antibiotic resistance . Using PCR primers, 500- to 700-bp amplicons surrounding the quinolone resistance determining regions (QRDR) of gyrA, gyrB, parC, and parE genes were prepared from each strain . Internal primers were used to sequence both DNA strands in the regions of approximately 400 bp centered on the QRDR . Mutations identified with increasing levels of resistance included changes in GyrA at Ser-81 and Glu-85 and changes in ParC at Ser-79 and Asp-83 . Changes in GyrB and ParE were not observed at the levels of resistance obtained in this selection . The resistance to comparator quinolones (levofloxacin, ciprofloxacin, and moxifloxacin) also increased in four- to eightfold steps with these mutations . The intrinsically greater level of antibacterial activity and thus lower MICs of BMS-284756 observed at all resistance levels in this study may translate to coverage of these resistant pneumococcal strains in the clinic. Antimicrob Agents Chemother, 2001 Oct, 45(10), 2793 - 7 Pharmacodynamics of fluoroquinolones against Streptococcus pneumoniae in patients with community-acquired respiratory tract infections; Ambrose PG et al.; Fluoroquinolone antibiotic agents have demonstrated efficacy in the treatment of respiratory tract infections . This analysis was designed to examine the relationship between drug exposure, as measured by the free-drug area under the concentration-time curve at 24 h (AUC(24))/MIC ratio, and clinical and microbiological responses in patients with community-acquired respiratory tract infections involving Streptococcus pneumoniae . The study population included 58 adult patients (34 males, 24 females) who were enrolled in either of two phase III, randomized, multicenter, double-blind studies of levofloxacin versus gatifloxacin for the treatment of community-acquired pneumonia or acute exacerbation of chronic bronchitis . Clearance equations from previously published population pharmacokinetic models were used in conjunction with dose and adjusted for protein binding to estimate individual patient free-drug AUC(24)s . In vitro susceptibility was determined in a central laboratory by broth microdilution in accordance with NCCLS guidelines . Pharmacodynamic analyses were performed on data from all evaluable patients with documented S . pneumoniae infection using univariate and multivariable logistic regression; pharmacodynamic breakpoints were estimated using Classification and Regression Tree analysis . A statistically significant (P = 0.013) relationship between microbiological response and the free-drug AUC(24)/MIC ratio was detected . At a free-drug AUC(24)/MIC ratio of <33.7, the probability of a microbiological response was 64%, and at a free-drug AUC(24)/MIC ratio of >33.7, it was 100% (P < 0.01) . These findings may provide a minimum target free-drug AUC(24)/MIC ratio for the treatment of infections involving S . pneumoniae with fluoroquinolone antibiotics and provide a paradigm for the selection of fluoroquinolones to be brought forward from drug discovery into clinical development and dose selection for clinical trials . Further, when target free-drug AUC(24)/MIC ratios are used in conjunction with stochastic modeling techniques, these findings may be used to support susceptibility breakpoints for fluoroquinolone antibiotics and S . pneumoniae. Antimicrob Agents Chemother, 2001 Oct, 45(10), 2765 - 70 Nasopharyngeal carriage of antimicrobial-resistant Streptococcus pneumoniae among young children attending 79 kindergartens and day care centers in Hong Kong; Chiu SS et al.; Resistance to penicillin and multiple antimicrobial agents among Streptococcus pneumoniae strains is becoming an increasing problem worldwide and in Asia . To determine the prevalence of carriage of S . pneumoniae isolates not susceptible to penicillin in young children, we obtained nasopharyngeal swab specimens from 1,978 children (ages, 2 to 6 years) attending 79 day care centers or kindergartens . Three hundred eighty-three strains of S . pneumoniae were isolated from these children . Fifty-eight percent of these isolates had reduced susceptibility to penicillin, 123 (32.1%) were intermediate, and 100 (26.1%) were resistant . A very high penicillin MIC (4 microg/ml) was found in 3.3% of the isolates . The isolates also demonstrated high rates of resistance to other antimicrobial agents (51.2% to cefaclor, 50.2% to cefuroxime, 42.8% to cefotaxime, 80.7% to trimethoprim-sulfamethoxazole, 77% to erythromycin, 60% to clindamycin, and 33.7% to chloramphenicol) . No isolate was resistant to fluoroquinolone . Multidrug resistance (not susceptible to the beta-lactams and three or more other classes) was found in 39.4% of the isolates . Risk factors for the carriage of S . pneumoniae not susceptible to penicillin were multiple physician visits in the preceding 3 months and use of antimicrobial agents by the individual or by household members in the preceding 3 months . In the logistic regression analysis, only the use of antimicrobial agents in the preceding 3 months was an independent risk factor (P = 0.004; odds ratio, 2; 95% confidence interval, 1.2 to 3.2) . This study demonstrated the high prevalence of antibiotic-resistant S . pneumoniae in healthy young children in the community in Hong Kong. Free Radic Biol Med, 2001 Sep 15, 31(6), 754 - 62 Oxidative stress in brain during experimental bacterial meningitis: differential effects of alpha-phenyl-tert-butyl nitrone and N-acetylcysteine treatment; Christen S et al.; Antioxidant treatment has previously been shown to be neuroprotective in experimental bacterial meningitis . To obtain quantitative evidence for oxidative stress in this disease, we measured the major brain antioxidants ascorbate and reduced glutathione, and the lipid peroxidation endproduct malondialdehyde in the cortex of infant rats infected with Streptococcus pneumoniae . Cortical levels of the two antioxidants were markedly decreased 22 h after infection, when animals were severely ill . Total pyridine nucleotide levels in the cortex were unaltered, suggesting that the loss of the two antioxidants was not due to cell necrosis . Bacterial meningitis was accompanied by a moderate, significant increase in cortical malondialdehyde . While treatment with either of the antioxidants alpha-phenyl-tert-butyl nitrone or N-acetylcysteine significantly inhibited this increase, only the former attenuated the loss of endogenous antioxidants . Cerebrospinal fluid bacterial titer, nitrite and nitrate levels, and myeloperoxidase activity at 18 h after infection were unaffected by antioxidant treatment, suggesting that they acted by mechanisms other than modulation of inflammation . The results demonstrate that bacterial meningitis is accompanied by oxidative stress in the brain parenchyma . Furthermore, increased cortical lipid peroxidation does not appear to be the result of parenchymal oxidative stress, because it was prevented by NAC, which had no effect on the loss of brain antioxidants. Oral Microbiol Immunol, 2001 Oct, 16(5), 319 - 20 Actinomyces naeslundii fimbrial protein Orf977 shows similarity to a streptococcal adhesin; Hoflack L et al.; The nucleotide sequence of the chromosomal DNA, upstream of Actinomyces naeslundii T14V fimbrial gene fimA, was determined . One open reading frame (orf977) encoding 977 amino acids was found, preceded by a gene homologous to elongation factor TU . Database searches revealed that Orf977 was homologous to CshA, a Streptococcus gordonii protein involved in cell adhesion . Previous studies had already determined two genes in the type 2 fimbrial gene cluster of A . naeslundii T14V: the structural subunit fimA, and orf365 with unknown function, followed by ribosomal genes . This study completes the type 2 fimbrial gene cluster sequence. J Biol Chem, 2001 Nov 30, 276(48), 45106 - 12 Epub 2001 Sep 11. Crystal structure of PBP2x from a highly penicillin-resistant Streptococcus pneumoniae clinical isolate: a mosaic framework containing 83 mutations; Dessen A et al.; Penicillin-binding proteins (PBPs) are the main targets for beta-lactam antibiotics, such as penicillins and cephalosporins, in a wide range of bacterial species . In some Gram-positive strains, the surge of resistance to treatment with beta-lactams is primarily the result of the proliferation of mosaic PBP-encoding genes, which encode novel proteins by recombination . PBP2x is a primary resistance determinant in Streptococcus pneumoniae, and its modification is an essential step in the development of high level beta-lactam resistance . To understand such a resistance mechanism at an atomic level, we have solved the x-ray crystal structure of PBP2x from a highly penicillin-resistant clinical isolate of S . pneumoniae, Sp328, which harbors 83 mutations in the soluble region . In the proximity of the Sp328 PBP2x* active site, the Thr(338) --> Ala mutation weakens the local hydrogen bonding network, thus abrogating the stabilization of a crucial buried water molecule . In addition, the Ser(389) --> Leu and Asn(514) --> His mutations produce a destabilizing effect that generates an "open" active site . It has been suggested that peptidoglycan substrates for beta-lactam-resistant PBPs contain a large amount of abnormal, branched peptides, whereas sensitive strains tend to catalyze cross-linking of linear forms . Thus, in vivo, an "open" active site could facilitate the recognition of distinct, branched physiological substrates. J Biol Chem, 2001 Nov 30, 276(48), 44551 - 6 Epub 2001 Sep 11. Substrate specificity of the streptococcal cysteine protease; Nomizu M et al.; The streptococcal pyrogenic exotoxin B (SpeB) is an important factor in mediating Streptococcus pyogenes infections . SpeB is the zymogen of the streptococcal cysteine protease (SCP), of which relatively little is known regarding substrate specificity . To investigate this aspect of SCP function, a series of internally quenched fluorescent substrates was designed based on the cleavage sites identified in the autocatalytic processing of SpeB to mature SCP . The best substrates for SCP contain three amino acids in the nonprimed position (i.e . AIK in P(3)-P(2)-P(1)) . Varying the length of the substrate on the primed side of the scissile bond has a relatively lower effect on activity . The highest activity (k(cat)/K(M) = 2.8 +/- 0.6 (10(5) x m(-1)s(-1)) is observed for the pentamer 3-aminobenzoic acid-AIKAG-3-nitrotyrosine, which spans subsites S(3) to S(2)' on the enzyme . High pressure liquid chromatography and mass spectrometry analyses show that the substrates are cleaved at the site predicted from the autoprocessing experiments . These results show that SCP can display an important level of endopeptidase activity . Substitutions at position P(2) of the substrate clearly indicate that the S(2) subsite of SCP can readily accommodate substrates containing a hydrophobic residue at that position and that some topological preference exists for that subsite . Substitutions in positions P(3), P(1), and P(1)' had little or no effect on SCP activity . The substrate specificity outlined in this work further supports the similarity between SCP and the cysteine proteases of the papain family . From the data regarding the identified or proposed natural substrates for SCP, it appears that this substrate specificity profile may also apply to the processing of mammalian and streptococcal protein targets by SCP. Infect Immun, 2001 Oct, 69(10), 6520 - 2 Regulation of Streptococcus gordonii sspB by the sspA gene product; El-Sabaeny A et al.; Streptococcus gordonii expresses two related adhesins, SspA and SspB, the genes for which are adjacent on the chromosome and are regulated independently . Although the adhesins are functionally similar, the sspA promoter is more active than that of sspB . In this study we show an additional role for SspA in the control of sspB activity . Gel shift and DNA footprinting assays demonstrate that the SspA protein binds to the sspB promoter and protects a region 233 to 264 bp upstream of the predicted -35 promoter element . The responsiveness of the sspB promoter to SspA was investigated with a promoter-cat reporter . Expression of the sspB promoter was reduced by over 60% in an SspA-deficient mutant of S . gordonii . These results indicate that expression of S . gordonii sspB is positively regulated by the sspA gene product. Infect Immun, 2001 Oct, 69(10), 6186 - 92 Proteins PblA and PblB of Streptococcus mitis, which promote binding to human platelets, are encoded within a lysogenic bacteriophage; Bensing BA et al.; The binding of platelets by bacteria is a proposed central mechanism in the pathogenesis of infective endocarditis . Platelet binding by Streptococcus mitis strain SF100 (an endocarditis isolate) was recently shown to be mediated in part by the surface proteins PblA and PblB . The genes encoding PblA and PblB are clustered with genes nearly identical to those of streptococcal phages r1t, 01205, and Dp-1, suggesting that pblA and pblB might reside within a prophage . To address this possibility, cultures of SF100 were exposed to either mitomycin C or UV light, both of which are known to induce the lytic cycle of many temperate phages . Both treatments caused a significant increase in the transcription of pblA . Treatment with mitomycin C or UV light also caused a substantial increase in the expression of PblA and PblB, as detected by Western blot analysis of proteins in the SF100 cell wall . By electron microscopy, phage particles were readily visible in the supernatants from induced cultures of SF100 . The phage, designated SM1, had a double-stranded DNA genome of approximately 35 kb . Southern blot analysis of phage DNA indicated that pblA and pblB were contained within the SM1 genome . Furthermore, Western blot analysis of phage proteins revealed that both PblA and PblB were present in the phage particles . These findings indicate that PblA and PblB are encoded by a lysogenic bacteriophage, which could facilitate the dissemination of these potential virulence determinants to other bacterial pathogens. Infect Immun, 2001 Oct, 69(10), 6102 - 9 Effect on polymorphonuclear cell function of a human-specific cytotoxin, intermedilysin, expressed by Streptococcus intermedius; Macey MG et al.; Streptococcus intermedius is a member of the normal flora of the mouth but is also an opportunistic pathogen associated with purulent infections at oral and nonoral sites . Intermedilysin (ILY) has been shown to be a cytolysin capable of generating pores in the cell membrane of erythrocytes demonstrable by electron microscopy . This effect has been shown to be specific for human cells . Since polymorphonuclear cells (PMNs) are the main cell involved in innate immunity we investigated the effect of purified intermedilysin from Streptococcus intermedius on PMN function . Active ILY at a concentration of 40 ng/microl caused a significant decrease in the number of intact PMNs after 60 min . The active cytolysin, when compared with heat-inactivated ILY, did not appear to be chemotactic for the PMNs but did cause an increase in intracellular calcium, with increased cell surface CD11b expression, metabolic burst, and phagocytosis of Staphylococcus aureus . These findings may have implications for the role of ILY in deep-seated abscesses. Infect Immun, 2001 Oct, 69(10), 6055 - 63 Population dynamics of Streptococcus mitis in its natural habitat; Hohwy J et al.; The purpose of this study was to examine the genetic structure of the typical commensal Streptococcus mitis biovar 1 in its natural habitat in the human oral cavity and pharynx and to investigate the role that selected microbial properties and host, spatial, and temporal factors play in determining the structure of the bacterial population . Consecutive samples were collected from buccal and pharyngeal mucosal surfaces of two infants, their four parents, and two elderly individuals over a period of approximately 1 year . A total of 751 isolates identified as S . mitis biovar 1 were typed by restriction endonuclease analysis (REA) and representative clones were typed by multilocus enzyme electrophoresis (MLEE) . The genetic diversity of the S . mitis biovar 1 isolates collected from single infant hosts over a period of 9 to 10 months was found to be between 0.69 and 0.76, which is considerably higher than that previously observed for intestinal populations of Escherichia coli . The study provides evidence of the existence of both transient and persistent clones in adult individuals . In the two infants, however, none of 42 demonstrated clones were detected on more than a single occasion . Statistical calculations showed that the ability to persist was not distributed at random in the S . mitis biovar 1 population . However, neither immunoglobulin A1 protease activity nor the ability to bind alpha-amylase from saliva was a preferential characteristic of persistent genotypes . In contrast to current concepts of climax ecosystems, the species niche in the habitat appears to be maintained predominantly by a succession of clones rather than by stable strains . Several lines of evidence suggest that the major origin of "new" clones is the many other habitats in the respiratory tract that are occupied by this species. Infect Immun, 2001 Oct, 69(10), 6030 - 7 Surface-expressed mig protein protects Streptococcus dysgalactiae against phagocytosis by bovine neutrophils; Song XM et al.; The mig gene of Streptococcus dysgalactiae, a major bovine mastitis pathogen, encodes two plasma protein-binding receptors, alpha2-macroglobulin (alpha2-M) and immunoglobulin G (IgG) . In this study, the mig gene from one S . dysgalactiae isolate was cloned and expressed in Escherichia coli . The IgG receptor region encoded by mig was conserved in 16 S . dysgalactiae strains . An isogenic mig mutant was constructed by allele replacement mutagenesis of the wild-type gene in S . dysgalactiae . The IgG-binding activity was lost in the mig mutant strain, whereas the alpha2-M receptor activity was still expressed but was detected only in the culture supernatant . In flow cytometry phagocytosis and bacterial-colony-counting bactericidal assays, the wild-type strain was found to be significantly more resistant to phagocytosis and killing by bovine neutrophils (PMNs) than the mig mutant strain when bacteria were preincubated with bovine serum . We therefore speculate that the Mig protein of S . dysgalactiae plays a role in virulence of the bacteria by binding to the plasma protein alpha2-M or IgG and thus preventing phagocytosis by bovine PMNs. Infect Immun, 2001 Oct, 69(10), 5997 - 6003 Protection against Streptococcus pneumoniae elicited by immunization with pneumolysin and CbpA; Ogunniyi AD et al.; The need for the development of cheap and effective vaccines against pneumococcal disease has necessitated the evaluation of common virulence-associated proteins of Streptococcus pneumoniae as potential vaccine antigens . In this study, we examined the capacity of active immunization with a genetic toxoid derivative of pneumolysin (PdB) and/or a fragment of choline binding protein A (CbpA; also known as PspC, Hic, and SpsA) to protect mice from intraperitoneal challenge with medium to very high doses of a highly virulent capsular type 2 pneumococcal strain, D39 . The median survival times for mice immunized with the individual protein antigens in different adjuvant combinations were significantly longer than those for mice that received the respective adjuvants alone . Mice immunized with CbpA alone were significantly better protected than mice immunized with PdB alone . Correspondingly, the median survival times for mice that were immunized with a combination of PdB and CbpA were significantly longer than those for mice that received PdB alone but not significantly different from those that received CbpA alone . Mice immunized with the protein antigens in a mixture of monophospholipid A (MPL) and aluminium phosphate (AlPO4) adjuvants had higher antibody titers than mice that received the antigens in AlPO4 alone . Mice immunized with PdB in MPL plus AlPO4 were also significantly better protected than mice that received PdB in AlPO4 alone. Acta Med Port, 2001 May-Jun, 14(3), 367 - 70 {Necrotizing fasciitis after varicella}; Goncalves E et al.; Necrotizing fasciitis is a rare and severe infection characterised by extremely rapid progressive involvement of the superficial fascias and deep dermal layers of the skin, with resultant vasculitis and necrosis . The authors present three clinical cases of necrotizing fasciitis; all three patients previously had varicella rash, rapid progressive spreading erythema with severe pain and toxic shock syndrome . Two patients had positive cultures of b-haemolytic streptococcus . Early stage differential diagnosis with celulitis, aggressive antibiotic treatment and pediatric intensive care support are essential . However, the main therapy is early extensive surgical approach involving all indurate areas, down to and including the muscle fascia. Oper Dent, 2001 Sep-Oct, 26(5), 445 - 50 Effect of adhesives on the inhibition of secondary caries around compomer restorations; Itota T et al.; This study evaluated the effect of adhesives on the inhibition of secondary caries around compomer restorations in vitro . Two adhesive systems with a Bis-GMA resin, Scotch bond Multi-purpose (MP) and Single Bond (SB), and one adhesive system with no Bis-GMA resin, F2000 compomer primer/adhesive (PA), were used prior to placement of the compomer (F2000), and non-fluoride releasing resin composite (Z100) was used as a control . Class V cavities prepared on extracted human premolars were restored with various combinations of materials: F2000/MP, F2000/SB, F2000/PA, Z100/MP, Z100/SB and Z100/PA . The restored teeth were incubated in bacterial medium containing sucrose with Streptococcus mutans for two weeks after storage for 14 days . On microradiographs, the radio-opaque layers adjacent to the F2000 restorations were thick and clear, while the layers in the Z100 restorations were unclear . In the F2000 restorations, the mean thickness of the radio-opaque layers in the PA group was significantly greater than that of the MP and SB groups . In fluoride-releasing measurement, F2000 coated with PA showed a significantly higher amount of fluoride release than MP and SB, and no significant difference in the amount of fluoride release from uncoated F2000 . These results indicated that applying an adhesive without Bis-GMA resin to compomer restoration has no suppressive effect on the fluoride release from compomer and might be beneficial for inhibiting secondary caries in vitro. Microbiology, 1995 Oct, 141(Pt 10), 2729 - 38 Polypeptides associated with tufts of cell-surface fibrils in an oral Streptococcus; Jameson MW et al.; Cells of the oral bacterium Streptococcus oralis CN3410 produce lateral tufts of cell-surface fibrils of two lengths . Treatment of cells with trypsin resulted in loss of the tufts and release of longer fibrils intact . SDS-PAGE analysis of trypsin extracts containing fibrils revealed two groups of high molecular mass polypeptides which were denoted group A (molecular mass 227-246 kDa) and group B (molecular mass 175-208 kDa) . Antibodies were raised to these two groups of trypsin-extracted polypeptides (TEPs) and to purified fibrils, and the reactivities of the three different antisera were found to be similar both on nitrocellulose blots of cell-surface polypeptides and in ELISA with whole cells . Similar patterns of TEPs were obtained from cells of a spontaneously derived mutant strain, KP34V, which lacked the short fibril components of tufts . Cells of strain KP34V had similar cell-surface hydrophobicity to strain CN3410 cells, and adhered to the same extent to parotid salivary pellicle or human buccal epithelial cells (BECs) as the wild-type cells . Trypsin treatment of strain CN3410 cells abolished their surface hydrophobicity and ability to adhere to BECs, but did not affect streptococcal cell binding to experimental salivary pellicle . Antibodies to TEPs or fibrils had no effect on cell adhesion to BECs or salivary pellicle . The results imply that the short fibril components of tufts are not involved in the cell adhesion properties tested . It is suggested that the TEPs are components of long fibrils, but they are not determinants of streptococcal cell adhesion to pellicle or to epithelial cells. Clin Infect Dis, 2001 Oct 15, 33(8), e93 - 6 Epub 2001 Sep 05. Emergence of rifampin-resistant Streptococcus pneumoniae as a result of antimicrobial therapy for penicillin-resistant strains; van Tilburg PM et al.; A multidrug-resistant strain of Streptococcus pneumoniae was isolated in The Netherlands during a nosocomial outbreak among 36 patients who mainly had chronic obstructive pulmonary disease . After the commencement of barrier nursing and short-term ceftriaxone-rifampin eradication therapy, the epidemic ceased . However, eradication therapy failed in 3 patients, and follow-up investigation of these patients showed the emergence of rifampin-resistant isolates. Pediatr Neurosurg, 2001 Aug, 35(2), 82 - 9 Intracranial complications of frontal sinusitis in children: Pott's puffy tumor revisited; Bambakidis NC et al.; The objective of the present study is to describe the diagnosis and treatment of intracranial complications of frontal sinusitis (Pott's puffy tumor) in a series of pediatric patients at our institution . A rare entity, Pott's puffy tumor has been reported in only 21 pediatric cases in the literature of the antibiotic era . The hospital records and radiographic files at Rainbow Babies and Childrens Hospital, Cleveland, Ohio, USA, over the previous 16 years were retrospectively reviewed in a search for patients with the diagnosis of Pott's puffy tumor, defined as scalp swelling and associated intracranial infection . There were 6 male patients and 1 female patient . Ages ranged from 11 to 18 years (median 14.5 years) . Intracranial infections consisted of epidural abscess in 5 patients, subdural empyema in 4 and brain abscess in 1 . Intraoperative cultures grew anaerobic organisms in 1 patient, microaerophilic streptococcus in 5 patients, Klebsiella species in 1 patient and Streptococcus pneumoniae in another . All patients presented with frontal scalp swelling, and other common symptoms included headache, fever, nasal drainage and frontal sinus tenderness . Five patients were treated with antibiotics prior to their presentation . Four patients presented with neurologic decompensation characterized by varying degrees of hemiparesis, obtundation, pupillary dilatation or aphasia . All patients underwent craniotomy and evacuation of the intracranial infection . Even severely impaired patients demonstrated full neurologic recovery . Despite the widespread use of antibiotics, neurosurgical complications of sinusitis continue to occur . A high degree of suspicion, along with prompt neurosurgical intervention and the use of appropriate antibiotics, can result in favorable outcomes in even the sickest patients . J Med Microbiol, 2001 Sep, 50(9), 828 - 32 Alterations to penicillin-binding proteins 1A, 2B and 2X amongst penicillin-resistant clinical isolates of Streptococcus pneumoniae serotype 23F from the nasopharyngeal flora of children; Ferroni A et al.; Various amino acid substitutions were identified in the three major penicillin-binding proteins (PBP1A, PBP2B and PBP2X) of eight clinical isolates of Streptococcus pneumoniae serotype 23F collected from children . The particular changes related to the level of penicillin resistance . Alterations were detected in an isolate with a penicillin MIC as low as 0.06 mg/L . These results confirm that the level of penicillin resistance in pneumococci reflects with sequential alterations of PBPs in clinical isolates. J Med Microbiol, 2001 Sep, 50(9), 812 - 21 Tumour necrosis factor-alpha causes an increase in blood-brain barrier permeability during sepsis; Tsao N et al.; Blood-brain barrier (BBB) permeability during sepsis with Escherichia coli or Streptococcus pneumoniae was examined in a mouse model and measured by a circulating beta-galactosidase tracer . The leakage of brain microvascular vessels during sepsis was confirmed by transmission electron microscopic examination of brain tissues stained with horseradish peroxidase . The increase of BBB permeability induced by E . coli and S . pneumoniae, which was maximal at 3 h and 12 h after injection, respectively, was transient because of rapid clearance of the bacteria from the blood . Tumour necrosis factor-alpha (TNF-alpha) was stained on microvascular vessels of the brain during sepsis and intravenous injection of recombinant TNF-alpha also increased the BBB permeability . The increase in BBB permeability induced by either E . coli or S . pneumoniae could be inhibited by anti-TNF-alpha antibody . It was concluded that circulating TNF-alpha generated during sepsis induced the increase in BBB permeability. Appl Microbiol Biotechnol, 2001 Aug, 56(3-4), 531 - 8 The impact of fermentative organisms on carbon flow in methanogenic systems under constant low-substrate conditions; Dollhopf SL et al.; We compared carbon flow under constant low-substrate conditions (below 20 microM glucose in situ) in laboratory-scale glucose-fed methanogenic bioreactors containing two very different microbial communities that removed chemical oxygen demand at similar rates . One community contained approximately equal proportions of spiral and cocci morphologies, while the other community was dominated by cocci . In the former bioreactor, over 50% of the cloned SSU rRNA genes and the most common SSU rDNA terminal restriction fragment corresponded to Spirochaetaceae-related sequences, while in the latter bioreactor over 50% of the cloned SSU rRNA genes and the most common SSU rDNA terminal restriction fragment corresponded to Streptococcus-related sequences . Carbon flow was assessed by measuring 14C-labeled metabolites derived from a feeding of {U-14C}glucose that did not alter the concentration of glucose in the bioreactors . Acetate and ethanol were detected in the Spirochaetaceae-dominated reactor, whereas acetate and propionate were detected in the Streptococcus-dominated reactor . A spirochete isolated from a Spirochaetaceae-dominated reactor fermented glucose to acetate, ethanol, and small amounts of lactate . Maximum substrate utilization assays carried out on fluid from the same reactor indicated that acetate and ethanol were rapidly utilized by this community . These data indicate that an acetate- and ethanol-based food chain was present in the Spirochaetaceae-dominated bioreactor, while the typical acetate- and propionate-based food chain was prevalent in the Streptococcus-dominated bioreactor. Salud Publica Mex, 2001 Jul-Aug, 43(4), 352 - 67 Meeting the challenge: prevention of pneumococcal disease with conjugate vaccines; Echaniz-Aviles IG et al.; Streptococcus pneumoniae is one of the leading causes of both invasive and noninvasive diseases in the pediatric population and continues to represent a significant public health burden worldwide . The increasing incidence of antibioticresistant strains of the pathogen has complicated treatment and management of the various pneumococcal disease manifestations . Thus, the best management strategy may be the prevention of pneumococcal diseases through vaccination . Although several pneumococcal conjugate vaccines have been clinically studied in infants and children, only a 7-valent conjugate vaccine (PNCRM7; Prevnar/Prevenar) is currently approved for the prevention of invasive disease . Vaccination with PNCRM7 is safe and effective in infants and young children . Routine vaccination with the conjugate vaccine could improve outcomes by safeguarding against the development of antibiotic-resistant strains of S . pneumoniae, thus simplifying the management of pneumococcal disease . Additionally, the overall costs associated with the treatment of pneumococcal diseases could be substantially reduced, particularly in developing countries . The time has come for fully applying this new advancement against S . pneumoniae, to benefit the children of the world . The English version of this paper is available at: http://www.insp.mx/salud/index.html Harefuah, 2001 Aug, 140(8), 704 - 5, 807 {Primary peritonitis due to Streptococcus pyogenes}; Shukha A et al.; Most infections causing by Streptococcus pyogenes are known to be putrid both in adults and children, for example laryngitis, impetigo, cellulitis, scarlet fever, septic shock, toxic shock syndrome etc . Their clinical importance relates to a number of causes: 1) about 20% of the population are S . pyogenes carriers; 2) the clinical course of infections is often severe or even fatal; 3) there is real danger of nosocomial outbursts; 4) a world-wide increase in both the rate and invasiveness of the microbe . Acute primary peritonitis due to S . pyogenes seems to be a rare clinical event . In order to stimulate physicians' attention to the issue, we decided to describe the case of a child with the primary peritonitis due to S . pyogenes . Early diagnosis and surgical intervention combined with the proper antibiotic treatment appeared to be life-saving. J Biol Chem, 2001 Nov 9, 276(45), 41790 - 6 Epub 2001 Sep 06. Similarities between complement-mediated and streptolysin S-mediated hemolysis; Carr A et al.; The oxygen-stable hemolysin streptolysin S (SLS) of Streptococcus pyogenes is encoded in part by the pel/sagA gene product . Antibodies to a synthetic peptide from the C terminus of the Pel/SagA open reading frame inhibited hemolysis mediated by both culture supernatants from multiple M serotypes of S . pyogenes isolates or a commercially available SLS preparation . Analysis of the SLS-mediated hemolytic reaction demonstrated that it was temperature- and concentration-dependent . Like complement-mediated hemolysis it conforms to the prediction of a one-hit mechanism of hemolysis . A number of intermediates in the SLS-mediated hemolysis of sheep erythrocytes could be distinguished . SLS could bind to erythrocytes below 17 degrees C; however, lysis could only occur at temperatures >23 degrees C . Following binding of SLS and washing, a papain-sensitive intermediate could be distinguished prior to insertion of the SLS complex into the erythrocyte membrane, which resulted in formation of a transmembrane pore and led to irreversible osmotic lysis of the cell . These intermediates were similar to those described previously during complement-mediated hemolysis. J Infect, 2001 May, 42(4), 272 - 7 Necrotizing fasciitis due to penicillin-resistant Streptococcus pneumoniae: case report and review of the literature; Ballon-Landa GR et al.; Necrotizing fasciitis (NF) is a life-threatening infection involving rapid necrosis of subcutaneous and fascial tissues . Streptococcus pneumoniae (SPN) soft tissue infection is exceedingly uncommon, reported primarily in patients with immunosuppression or other underlying conditions . We report a case of NF and septic shock in a healthy 32-year-old man, whose only predisposing factor was antecedent blunt trauma . Pathological examination and culture of the extensive tissue debridement were positive only for SPN . The serotype 9V isolate was penicillin (PCN)-resistant (MIC=2.0), and closely-related by pulse field gel electrophoresis and multilocus fingerprinting to clone France 9V-3, an important genetic reservoir for increasing PCN-resistance worldwide . This unique case has implications for our pathogenic under-standing and empiric management of NF . J Infect, 2001 May, 42(4), 235 - 42 Contribution of alveolar phagocytes to antibiotic efficacy in an experimental lung infection with Streptococcus pneumoniae; Calame W et al.; OBJECTIVES: The effect of cyclophosphamide-induced leukocytopenia on the cellular defence and on the efficacy of penicillin treatment in a Streptococcus pneumoniae pneumonia model in mice was studied . METHODS: The number of alveolar phagocytes was determined in broncho-alveolar lavage (BAL) fluid as well as the number of bacteria in both BAL fluid and homogenized lung tissue . RESULTS: Eighteen and 21 h after infection, leukocytopenic animals had significantly lower numbers of alveolar phagocytes than controls, while the numbers of bacteria in both BAL fluid and lungs were significantly higher . The number of bacteria was inversely related to the dose of penicillin and the number of alveolar macrophages . The number of alveolar granulocytes was inversely related to the dose of penicillin . CONCLUSIONS: Leukocytopenia due to cyclophosphamide impairs the cellular defence in the lung against Streptococcus pneumoniae and the dose of penicillin must be increased to compensate for the higher outgrowth of bacteria in these leukocytopenic mice, compared to normal animals . J Infect, 2001 Apr, 42(3), 210 - 2 Streptococcus pneumoniae: a rare skin pathogen? Kalima P, Riordan T. Streptococcus pneumoniae is a rare cause of skin infections in adults . We present three cases and a review of the literature on this infection . Nine of the 42 (21%) cases occurred in previously healthy individuals without predisposing conditions . The majority of cases (88%) had bacteraemia . More than half the cases (22/42, 52%) required surgical intervention in addition to antimicrobial therapy . Infection, 2001 Aug, 29(4), 234 - 6 Spinal epidural abscess due to Streptococcus pneumoniae in an HIV-infected adult; Younus F et al.; Spinal epidural abscess (SEA) due to Streptococcus pneumoniae is rare and has never been reported in an HIV-infected patient, despite the higher risk of invasive disease in this group . We describe here the first case of pneumococcal epidural abscess, presenting with fever and back pain in a 60-year-old man infected with HIV . Blood cultures were positive for S . pneumoniae and magnetic resonance imaging (MRI) confirmed the suspicion of diskitis and SEA at the L4-S1 level . The patient was successfully treated with iv ceftriaxone without surgical intervention . The clinical characteristics of this case are compared with existing literature on pneumococcal SEA. Infection, 2001 Aug, 29(4), 201 - 4 Efficacy of clarithromycin in preventing viridans streptococcal bacteremia following autologous stem cell transplantation; Naqvi B et al.; BACKGROUND: In a study involving 200 patients, we previously found that 17.5% of patients developed viridans streptococcal (VS) bacteremia following autologous peripheral blood stem cell transplantation (aPBSCT) when ciprofloxacin or ciprofloxacin plus ampicillin was used for prophylaxis . PATIENTS AND METHODS: A retrospective evaluation of 100 consecutive recipients of aPBSCT was conducted to ascertain the incidence and outcome of VS bacteremia when a combination of ciprofLoxacin and clarithromycin was utilized for antimicrobiaL prophylaxis following transplantation . The 200 patients from our previous study, in which ciprofloxacin alone or ciprofloxacin with ampicillin was used for prophylaxis, were combined with the current group for the purpose of statistical analysis . RESULTS: Streptococcus mitis was isolated from the blood of five individuals at a median of 5 days following stem cell infusion . Each of these patients was neutropenic and presented with fever . Three isolates demonstrated intermediate resistance to macrolides in vitro . However, all episodes of bacteremia were treated successfully with systemic antibiotic therapy . CONCLUSION: Age, duration of neutropenia, type of underlying malignancy and type of conditioning chemotherapy regimen failed to have a significant impact on subsequent VS bacteremia . Only female sex and use of ciprofloxacin without clarithromycin as antimicrobiaL prophyLaxis predicted a significantly increased risk of VS bacteremia in both univariate and Logistic regression analyses. Clin Experiment Ophthalmol, 2001 Aug, 29(4), 260 - 1 Fulminant orbital cellulitis with complete loss of vision; Connell B et al.; Bacterial orbital cellulitis is a condition that rarely presents with complete loss of vision . A case is reported of a 69-year-old man who presented with fulminant onset of proptosis, significant ophthalmoplegia and no perception of light . Computed tomography showed no evidence of paranasal sinus disease . Despite treatment with intravenous flucloxacillin, ceftriaxone and metronidazole, and later, penicillin after Streptococcus pyogenes was grown from tissue culture, there was no improvement in vision; however ocular motility returned to normal. Odontostomatol Trop, 2001 Jun, 24(94), 19 - 22 {Septicemia of dental origin and post-extraction coma . Apropos of 3 cases}; Ngapeth-Etoundi M et al.; The authors report 3 cases of septicaemia and coma post dental extraction . These 3 patients had dental extraction in the same confessional dental clinic . After these acts the situation were so severe and they came to central hospital in Yaounde . Infections from dental origin proven by blood culture necessitate an early antibiotherapy and treatment, which propriate and sustain, but adapted to the antibiogram . The streptococcus of group F and Klebsiella pneumonia were challenged . One of the cases was negative . The presence of common signs (fever, tachycardia, chill) need the search for a secondary localisation which can be determine by X-ray. J Allergy Clin Immunol, 2001 Sep, 108(3), 424 - 9 Allergic inflammation enhances bacterial sinusitis in mice; Blair C et al.; BACKGROUND: Although it is not proven, one factor considered important in the development of sinusitis is allergic rhinitis . OBJECTIVE: The purpose of this study was to determine whether ongoing allergic rhinitis enhances the infection and inflammation associated with Streptococcus pneumoniae acute sinus infection . METHODS: BALB/c mice were sensitized to ovalbumin by intraperitoneal injection . After infection of the sinuses by S pneumoniae, either with or without concomitant administration of ovalbumin to induce allergic inflammation, mice were killed at various times and their heads were prepared for histologic evaluation of the sinuses . RESULTS: Mice became allergic to ovalbumin and developed eosinophilia in the sinus and lung cavities in response to ovalbumin administration to each of the respective cavities . In comparison with controls, the mice with ongoing nasal allergic inflammation that were inoculated with S pneumoniae had significantly more bacteria recovered at sacrifice and had significantly more inflammation, as indicated by neutrophil, eosinophil, and mononuclear influx into the sinus mucosa . The percentage of the sinus area occupied by neutrophil clusters was also increased after infection in the allergic mice in comparison with the control mice . CONCLUSION: Our data demonstrate that mice can be sensitized to ovalbumin and develop a localized allergic reaction in the skin, nose, or lung . An ongoing local allergic response augments bacterial infection in these animals . We also demonstrate that allergic sensitization alone, allergen exposure alone, or an allergic response at a distal site, the lung, does not augment the sinus infection. J Bacteriol, 2001 Oct, 183(19), 5709 - 17 Genome of the bacterium Streptococcus pneumoniae strain R6; Hoskins J et al.; Streptococcus pneumoniae is among the most significant causes of bacterial disease in humans . Here we report the 2,038,615-bp genomic sequence of the gram-positive bacterium S . pneumoniae R6 . Because the R6 strain is avirulent and, more importantly, because it is readily transformed with DNA from homologous species and many heterologous species, it is the principal platform for investigation of the biology of this important pathogen . It is also used as a primary vehicle for genomics-based development of antibiotics for gram-positive bacteria . In our analysis of the genome, we identified a large number of new uncharacterized genes predicted to encode proteins that either reside on the surface of the cell or are secreted . Among those proteins there may be new targets for vaccine and antibiotic development. FEMS Microbiol Ecol, 1996 Jul, 20(3), 155 - 62 Survival of potentially pathogenic human-associated bacteria in the rhizosphere of hydroponically grown wheat; Morales A et al.; Plants may serve as reservoirs for human-associated bacteria (H-AB) in long-term space missions containing bioregenerative life support systems . The current study examined the abilities of five human-associated potential pathogens, Pseudomonas aeruginosa, Pseudomonas cepacia, Staphylococcus aureus, Streptococcus pyogenes and Escherichia coli, to colonize and grow in the rhizosphere of hydroponically grown wheat, a candidate crop for life support . All of these bacteria have been recovered from past NASA missions and present potential problems for future missions . The abilities of these organisms to adhere to the roots of axenic five-day-old wheat (Triticum aestivum L . cv . Yecora rojo) were evaluated by enumeration of the attached organisms after a one hour incubation of roots in a suspension (approximately 10(8) cfu ml-1) of the H-AB . Results showed that a greater percentage of P . aeruginosa cells adhered to the wheat roots than the other four H-AB . Similarly incubated seedlings were also grown under attempted axenic conditions for seven days to examine the potential of each organism to proliferate in the rhizosphere (root colonization capacity) . P . cepacia and P . aerogiunosa showed considerable growth, E . coli and S . aureus showed no significant growth, and S . pyogenes died off in the wheat rhizosphere . Studies examining the effects of competition on the survival of these microorganisms indicated that P . aeruginosa was the only organism that survived in the rhizosphere of hydroponically grown wheat in the presence of different levels of microbial competition. Microbiology, 2001 Sep, 147(Pt 9), 2469 - 77 H(2)O(2)-nonproducing Streptococcus pyogenes strains: survival in stationary phase and virulence in chronic granulomatous disease; Saito M et al.; The production of hydrogen peroxide (H(2)O(2)) and related phenotypes were studied with Streptococcus pyogenes strains isolated from cases of pharyngitis or severe group A streptococcal infections . Of the 46 strains examined (34 from severe infections and 12 from pharyngitis cases), 25 strains accumulated H(2)O(2) in the culture medium when grown under glucose-limited, aerobic conditions, whereas the rest of the strains did not . There was no correlation between these traits and the type of disease from which each strain had been isolated . The H(2)O(2)-nonproducing strains tested in this study belonged to T type 3 or T type 12 . The accumulation of H(2)O(2) started when the culture reached the late exponential phase . A rapid loss of cell viability accompanied H(2)O(2) accumulation but was completely prevented by the addition of a catalase, indicating that the lethality was actually caused by H(2)O(2) . Cells of H(2)O(2)-nonproducing strains were resistant to killing by phagocytes from patients with chronic granulomatous disease (CGD), whereas those of H(2)O(2)-producing strains were subject to killing . Subcutaneous inoculation of 10(5) c.f.u . H(2)O(2)-nonproducing S . pyogenes strains into the hind footpads of CGD mice provoked more prominent swelling of the footpad than did H(2)O(2)-producing strains . The mortality rate in the CGD mice infected with the H(2)O(2)-nonproducing strains was higher than that produced by the H(2)O(2)-producing strains . It is suggested that H(2)O(2)-nonproducing S . pyogenes strains are prevalent in humans and that they may be a potential threat to the health of CGD patients. Vaccine, 2001 Sep 14, 19(32), 4780 - 90 Efficacy of pneumococcal polysaccharide vaccine in immunocompetent adults: a meta-analysis of randomized trials; Cornu C et al.; The use of pneumococcal polysaccharide vaccine (PPV) is low in some countries, maybe because of doubts regarding its efficacy . This meta-analysis aims at combining evidence from randomized trials of PPV assessing its efficacy in preventing Streptococcus pneumoniae related diseases in immunocompetent adults . In the fourteen trials totalling 48,837 patients retrieved, PPV prevents definite pneumococcal pneumonia by 71%, presumptive pneumococcal pneumonia by 40%, and mortality due to pneumonia by 32%, but not all-cause pneumonia or death . No preventive effect was seen in the subgroup of patients aged 55 years or more, possibly due to a lack of statistical power. Prev Vet Med, 2001 Oct 11, 51(3-4), 307 - 16 Application of the California mastitis test in intramammary Streptococcus agalactiae and Staphylococcus aureus infections of camels (Camelus dromedarius) in Kenya; Younan M et al.; A study was conducted on 207 lactating camels in six herds in Kenya to evaluate the California mastitis test (CMT) for the detection of intramammary infections (IMIs) caused by Streptococcus agalactiae and Staphylococcus aureus and to investigate the prevalence of both the pathogens in the camel udder . IMI with S . agalactiae was found in 12% of all camels sampled . IMI with S . aureus was present in 11% of all camels sampled . The herd-level prevalence of IMI varied between 0 and 50% for S . agalactiae and between 0 and 13% for S . aureus . Longitudinal observations over 10-12 months confirmed persistent infections for both pathogens . Observations in one herd suggested that camel pox was a contributing factor in spreading and exacerbating S . agalactiae udder infections.The CMT had quarter-level sensitivities of 77 and 68% for S . agalactiae and S . aureus in camels, respectively . The CMT specificities were 91% for both the pathogens. Respir Physiol, 2001 Oct, 128(1), 23 - 31 The role of immunity in susceptibility to respiratory infection in the aging lung; Meyer KC; Respiratory tract infections, particularly pneumonia, are a leading cause of death in persons 65 years or older in both developed and developing countries . Because many attributes of immunity wane with advancing age, the elderly may be more susceptible to respiratory infections, even if they appear to be in good health . A decline in the ability of lymphoid tissues to mount an antigen-specific response (adaptive immunity) to specific microorganisms such as influenza virus or Streptococcus pneumoniae is thought to be an important factor in increasing susceptibility to respiratory tract infection with advancing age . However, abnormalities in innate immunity may also contribute to increased susceptibility to respiratory infections and have been poorly characterized in the elderly . Although changes in immune parameters such as T cell subsets and immunoglobulin concentrations have been observed in respiratory secretions from older healthy individuals compared to younger subjects, the significance of these changes for protective immunity in the lung is unknown . The incidence of pneumonia may be lessened by measures such as optimizing treatment of comorbid conditions, optimizing nutrition, and addressing swallowing disorders . The use of vaccines directed against the influenza virus and S . pneumoniae appears to have made an impact on the degree of morbidity and mortality, and perhaps, the incidence, of community-acquired pneumonia . However, better stimulation of specific immune responses with improved vaccines and more widespread use of these vaccines for protection of elderly individuals are needed. Biochem J, 2001 Sep 15, 358(Pt 3), 529 - 38 Carbohydrate specificity of a galectin from chicken liver (CG-16); Wu AM et al.; Owing to the expression of more than one type of galectin in animal tissues, the delineation of the functions of individual members of this lectin family requires the precise definition of their carbohydrate specificities . Thus, the binding properties of chicken liver galectin (CG-16) to glycoproteins (gps) and Streptococcus pneumoniae type 14 polysaccharide were studied by the biotin/avidin-mediated microtitre-plate lectin-binding assay and by the inhibition of lectin-glycan interactions with sugar ligands . Among 33 glycans tested for lectin binding, CG-16 reacted best with human blood group ABO (H) precursor gps and their equivalent gps, which contain a high density of D-galactopyranose(beta1-4)2-acetamido-2-deoxy-D-glucopyranose {Gal(beta1-4)GlcNAc} and Gal(beta1-3)GlcNAc residues at the non-reducing end, but this lectin reacted weakly or not at all with A-,H-type and sialylated gps . Among the oligosaccharides tested by the inhibition assay, the tri-antennary Gal(beta1-4)GlcNAc (Tri-II) was the best . It was 2.1x10(3) nM and 3.0 times more potent than Gal and Gal(beta1-4)GlcNAc (II)/Gal(beta1-3)GlcNAc(beta1-3)Gal(beta1-4)Glc (lacto-N-tetraose) respectively . CG-16 has a preference for the beta-anomer of Gal at the non-reducing end of oligosaccharides with a Gal(beta1-4) linkage >Gal(beta1-3)> or =Gal(beta1-6) . From the results, it can be concluded that the combining site of this agglutinin should be a cavity type, and that a hydrophobic interaction in the vicinity of the binding site for sugar accommodation increases the affinity . The binding site of CG-16 is as large as a tetrasaccharide of the beta-anomer of Gal, and is most complementary to lacto-N-tetraose and Gal(beta1-4)GlcNAc related sequences. An Med Interna, 2001 Jul, 18(7), 379 - 80 {Endophthalmitis and multiple brain abscess in a patient with endocarditis due to Streptococcus agalactiae}; Pena Jimenez D et al.; Endogenous endophthalmitis is a rare disease caused by hematogenic germ spread from an internal focus . Infections due to Streptococcus agalactiae are infrequent in adults although new cases had been described recently associated to inmunodepression . We present a patient with endocarditis due to Streptococcus agalactiae, endophthalmitis and multiple brain abscess . We also review the literature. Pediatrics, 2001 Sep, 108(3), 575 - 83 A community intervention trial to promote judicious antibiotic use and reduce penicillin-resistant Streptococcus pneumoniae carriage in children; Belongia EA et al.; OBJECTIVE: Inappropriate use of antibiotics is common in primary care, and effective interventions are needed to promote judicious antibiotic use and reduce antibiotic resistance . The objective of this study was to assess the impact of parent and clinician education on pediatric antibiotic prescribing and carriage of penicillin-nonsusceptible Streptococcus pneumoniae in child care facilities . METHODS: A nonrandomized, controlled, community intervention trial was conducted in northern Wisconsin Clinicians . Clinic staff received educational materials and small-group presentations; materials were distributed to parents through clinics, child care facilities, and community organizations . Prescribing data were analyzed for 151 clinicians who provided primary pediatric care; nasopharyngeal carriage of penicillin-nonsusceptible S pneumoniae was assessed for 664 children in the baseline period (January-June 1997) and for 472 children in the postintervention period (January-June 1998) . RESULTS: The median number of solid antibiotic prescriptions per clinician declined 19% in the intervention region and 8% in the control region . The median number of liquid antibiotic prescriptions per clinician declined 11% in the intervention region, compared with an increase of 12% in the control region . Retail antibiotic sales declined in the intervention region but not in the control region . Among participating children in child care facilities, there were no significant differences in antibiotic use or penicillin-nonsusceptible S pneumoniae colonization between the intervention and control regions . CONCLUSIONS: A multifaceted educational program for clinicians and parents led to community-wide reductions in antibiotic prescribing, but in child care facilities, there was no apparent impact on judicious antibiotic use or colonization with drug-resistant S pneumoniae . Longer follow-up time or greater reductions in antibiotic use may be required to identify changes in the pneumococcal susceptibility. J Antimicrob Chemother, 2001 Sep, 48(3), 441 - 4 Antibiotic use and resistance of Streptococcus pneumoniae in The Netherlands during the period 1994-1999; de Neeling AJ et al.; Antibiotic use in The Netherlands during the period 1994-1999 is described in relation to the resistance of routine isolates of Streptococcus pneumoniae . The average antibiotic use in the study period was 3.4 defined daily doses per 1000 persons per day (DDD/1000/day) penicillins, 0.066 DDD/1000/day beta-lactams other than penicillins, 2.3 DDD/1000/day tetracyclines and 0.71 DDD/1000/day trimethoprim and sulphonamides, without apparent rise or decline . In contrast, the use of macrolides doubled from 0.51 DDD/1000/day in 1994 to 1.0 DDD/1000/day in 1997 and stayed at 1.07 DDD/1000/day in 1998 and 1999 . In 1994 the first pneumococci isolated from patients showed 0.7% resistance to penicillin (intermediate plus full resistance), 2.5% to erythromycin, 4.2% to co-trimoxazole and 4.7% to tetracycline . In 1999 first isolates showed 1.5% resistance to penicillin, 3.8% to erythromycin, 4.4% to co-trimoxazole and 6.6% to tetracycline . The modest but significant rise in the resistance to erythromycin may have been caused by the increased use of macrolides in the years 1994-1997 . The rise in resistance to penicillin seemed not to be related to increased beta-lactam use. J Antimicrob Chemother, 2001 Sep, 48(3), 411 - 6 In vitro selection of resistance to clindamycin related to alterations in the attenuator of the erm(TR) gene of Streptococcus pyogenes UCN1 inducibly resistant to erythromycin; Fines M et al.; A clinical isolate of Streptococcus pyogenes UCN1 intermediate to erythromycin (MIC 1 mg/L) and susceptible to clindamycin (MIC 0.03 mg/L) harboured an inducible erm(TR) gene encoding a ribosomal methylase . We have selected in vitro, in the presence of concentrations of clindamycin ranging from 0.12 to 1 mg/L, one-step mutants that are highly resistant to this antibiotic (MIC 64 mg/L) at a frequency of 10(-7) . By contrast, in an erythromycin-susceptible strain of S . pyogenes UCN5, mutants could be selected only by a low concentration of clindamycin (0.12 mg/L) at a frequency of 10(-9) . Clindamycin resistance in four of six S . pyogenes UCN1 mutants was associated with deletions of 163 and 6 bp, as well as a tandem duplication of 101 bp in the regulatory sequence of the erm(TR) gene . The role of these structural alterations in clindamycin resistance was demonstrated by cloning the erm(TR) gene from the wild-type and mutant strains in Escherichia coli DB10, a mutant susceptible to macrolides . Clindamycin resistance was expressed only when the erm(TR) gene was preceded by an altered attenuator . Mutations could lead to the formation of mRNA secondary structures accounting for the accessibility of the ribosome-binding site and the initiation codon of the ErmTR methylase to the ribosomes, and subsequently for the translation of the erm(TR) transcripts . The easy selection in one step of mutants resistant to high levels of clindamycin by concentrations of this antibiotic ranging from four to 40 times the MIC leads us to recommend caution in the use of clindamycin therapy in group A Streptococcus infections. J Antimicrob Chemother, 2001 Sep, 48(3), 407 - 9 In vitro activity of a novel ketolide ABT-773 against invasive strains of Streptococcus pneumoniae; Weiss K et al.; New ketolides such as ABT-773 are a promising group of antibiotics in an era of increasing antibiotic resistance . We tested 704 invasive strains of Streptococcus pneumoniae collected from 1990 to 1998 . Overall resistance was 8.3, 4.6, 4.5 and 3.6% for penicillin, cefuroxime, erythromycin and clarithromycin, respectively . By using a recommended breakpoint for susceptibility of <0.5 mg/L, no strains showed reduced susceptibility to ABT-773 . ABT-773 was very active against all penicillin-resistant strains (MIC > 2 mg/L, with a mean geometric mean <0.06 mg/L), and against all 33 erythromycin-resistant strains, irrespective of the mode of resistance {mef- or erm(B)-mediated} . ABT-773 is a very active and promising agent against invasive strains of S . pneumoniae, including multiresistant strains. J Antimicrob Chemother, 2001 Sep, 48(3), 365 - 74 Single- and multi-step resistance selection study of gemifloxacin compared with trovafloxacin, ciprofloxacin, gatifloxacin and moxifloxacin in Streptococcus pneumoniae; Nagai K et al.; The ability of sequential subcultures in subinhibitory concentrations of gemifloxacin, trovafloxacin, ciprofloxacin, gatifloxacin and moxifloxacin to select resistant mutants was studied in 16 pneumococci {eight with ciprofloxacin MICs (mg/L) 0.25-1; four with 8-16; four with 16-32} . Subculturing was done 50 times, or until mutants with elevated MICs (> or = 4 x) to the selecting drug emerged . Subculturing in gemifloxacin selected six resistant mutants (gemifloxacin MICs 2 mg/L); trovafloxacin selected nine (trovafloxacin MICs 2-4 mg/L); ciprofloxacin selected 11 (ciprofloxacin MICs 8-128 mg/L); gatifloxacin selected 13; and moxifloxacin selected 12 (gatifloxacin or moxifloxacin MICs 2-16 mg/L) . DNA sequencing showed that most mutants had mutations in ParC at Ser-79 or Asp-83 and in GyrA at Ser-81 or Glu-85; some mutants also had mutations in ParE or GyrB . Some new mutations were found in ParE or GyrB that have not yet been reported; GyrB mutation might be associated with moxifloxacin resistance . Both DNA gyrase and topoisomerase IV were thought to be the target of gemifloxacin; gemifloxacin also selected mutants with single modifications in gyrA, parC or parE alone among derived mutants by repeated exposure to subinhibitory concentrations of fluoroquinolones . In the presence of reserpine, most mutants had lower MICs of ciprofloxacin and gemifloxacin (4-32 x), and gatifloxacin (4-8 x), suggesting an efflux mechanism; none had lower trovafloxacin and moxifloxacin MICs . All quinolones tested selected for resistance; judicious use and proper dosing will be necessary to avoid resistance selection of newer broad-spectrum fluoroquinolones. Clin Microbiol Infect, 2001 Jul, 7(7), 362 - 6 In vitro activity of midecamycin diacetate, a 16-membered macrolide, against Streptococcus pyogenes isolated in France, 1995-1999; Schlegel L et al.; OBJECTIVE: To compare the in vitro activity of midecamycin diacetate to that of five other macrolides (erythromycin, clarithromycin, roxithromycin, azithromycin, and josamycin) and of clindamycin against 146 clinical isolates of Streptococcus pyogenes, with regard to three different phenotypes of erythromycin resistance . METHODS: Susceptibility pattern and resistance phenotype were determined by disk diffusion method and double disk test . Minimal inhibitory concentrations of antibiotics were obtained by the agar dilution method and evaluated according to the recommendations of the 'Comite de l'Antibiogramme de la Societe Francaise de Microbiologie' (CA-SFM) . The major determinants of erythromycin resistance in S . pyogenes (ermB, ermTR and mefA genes) were investigated by specific amplification protocols . RESULTS: Most of the isolates of S . pyogenes collected during 1995-99 were susceptible to midecamycin (93.8%), erythromycin (90.4%), clarithromycin (93.2%), roxithromycin (91.8%), azithromycin (88.4%), josamycin (94.5%), and clindamycin (94.5%) . According to the CA-SFM criteria, 132 of the 146 isolates studied were susceptible to erythromycin (MICs < or = 1 mg/L), four were intermediate (MICs 2-4 mg/L), and 10 were resistant (MICs > 4 mg/L) . Only nine isolates were midecamycin resistant (MICs > 4 mg/L), and the others were susceptible . The increased activity of midecamycin (MIC90 < or = 0.06 mg/L), as compared to erythromycin (MIC90 = 0.5 mg/L) and to other 14- or 15-membered macrolides, was related to the absence of the ermB determinant in seven isolates which displayed an efflux phenotype (five isolates) or an inducible resistance phenotype due to an ermTR determinant (two isolates) . CONCLUSION: Midecamycin diacetate is active against most S . pyogenes strains isolated in France and may represent an attractive alternative to the treatment of streptococcal infections due to resistant isolates with efflux of erythromycin. J Infect, 2001 Feb, 42(2), 116 - 9 Prevalence of liver disease in patients with Streptococcus bovis bacteraemia; Gonzlez-Quintela A et al.; BACKGROUND: The relationship between Streptococcus bovis bacteraemia and gastrointestinal disease (mainly colon cancer) is well known . Patients with advanced liver disease are prone to bacteraemia . Less attention has been paid to the association between liver disease and Streptococcus bovis bacteraemia in the literature . AIMS: To evaluate the prevalence of liver disease in patients with S . bovis bacteraemia . PATIENTS AND METHODS: Twenty-two episodes of S . bovis bacteraemia in 20 adults (13 males and seven females, with a median age of 61 years, range 32-94 years) were detected in a single hospital over a 7-year period . Ten of them had endocarditis . Patients' clinical records were reviewed, with special focus on underlying liver and gastrointestinal disease . RESULTS: Eleven patients (55%) had a chronic liver disease . Nine of them were cirrhotics . Ten patients had a history of chronic alcohol abuse, and four patients had hepatitis C virus antibodies (associated with alcohol abuse in three cases) . Large bowel disease was present in six out of 13 evaluable patients (adenocarcinoma in three cases) . Patients with liver disease were younger than patients without it . Mortality related to S . bovis bacteraemia was particularly high among patients with advanced liver disease (Child-Pugh state C) . Bacteraemia recurred two times in one alcoholic cirrhotic, who was diagnosed as having a Dukes-B colon cancer 4.5 years after the first episode of S . bovis bacteraemia . CONCLUSIONS: In our area, S . bovis bacteraemia is frequently associated with chronic liver disease . Liver disease may be a predisposing factor for S . bovis bacteraemia. Arch Otolaryngol Head Neck Surg, 2001 Aug, 127(8), 985 - 90 C57Bl/6 and BALB/c mice have similar neutrophil response to acute Streptococcus pneumoniae sinus infections; Gabr U et al.; BACKGROUND: Previous investigations have shown that mice with a tendency toward a T(H)1 or T(H)2 lymphocyte response manifest different reactions to inoculation with the parasite Leishmania major . BALB/c mice (with a tendency for a T(H)2 response) showed evidence of systemic infection, whereas C57Bl/6 mice (with a tendency for a T(H)1 response) showed only a local reaction . OBJECTIVE: To investigate whether BALB/c and C57Bl/6 mice respond differently to acute bacterial infection of the sinuses . METHODS: We inoculated the nasal cavities of C57Bl/6 and BALB/c mice with Streptococcus pneumoniae (type ATCC59), or with broth as a control . The mice were humanely killed 2, 5, 10, and 14 days after inoculation . Their heads were fixed, decalcified, and embedded in paraffin blocks . Sections were stained with hematoxylin and eosin, and the degree of inflammation was quantified by the number of neutrophils per square millimeter of the sinus mucosa and the percentage of the sinus cavity occupied by neutrophil clusters . RESULTS: Both groups of mice showed evidence of inflammation that was significantly greater than controls (P =.01), with no difference between groups . There was a correlation between the number of neutrophils per square millimeter in the sinus mucosa and the percentage of neutrophil clusters (C57Bl/6 mice, r = 0.37, P<.001; BALB/c mice, r = 0.20, P<.001) . In the infected mice, the number of infiltrating neutrophils was significantly greater (P<.001) in anatomically lower (dependent) areas of the sinuses compared with the upper areas . CONCLUSION: Unlike leishmaniasis, acute bacterial sinusitis is not affected by the tendency of the host to favor either a T(H)1 or T(H)2 response. AIDS Patient Care STDS, 2001 May, 15(5), 263 - 9 Successful prophylaxis against Pneumocystis carinii pneumonia in HIV-infected children using smaller than recommended dosages of trimethoprim-sulfamethoxazole; Fisher RG et al.; Prophylaxis against Pneumocystis carinii pneumonia (PCP) is an essential part of the management of children with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) . No dose-ranging studies were ever performed; therefore, the amount of trimethoprim-sulfamethoxazole (TMP-SMX) needed to suppress PCP in children with HIV/AIDS is not known . The dose recommended by the Centers for Disease Control (CDC) has been thought to be just above the threshold needed for prevention, based on anecdotal breakthrough PCP in cancer patients who were improperly dosed . We have been giving prophylaxis based on body weight rather than surface area, and this, combined with growth of our children, has led to a large experience with dosages lower than the currently recommended 150 mg/m2 . The medical records of children with HIV who met CDC guidelines for institution of PCP prophylaxis were reviewed . To ascertain the per square meter (m2) dosage each child was receiving, body surface area was calculated from height and weight measurements . Dosages were recalculated every 6 months and at each dosage change . Data regarding PCP infection, bacterial infections, and side effects of TMP-SMX were extracted . Data were compiled from 1,719.5 child-months of TMP-SMX prophylaxis, including 1,532.5 child-months below the currently recommended dose . Sixty-seven percent of our child-months were at or below two-thirds the CDC recommended dose . There were no cases of proven or suspected PCP . Incidence of other serious bacterial infections was low . Bacteremia and sepsis with Streptococcus pneumoniae was the most common proven bacterial infection, at a rate of 5.5 episodes per 100 child-years . The incidence of bacterial infection did not vary by the dose of TMP-SMX . TMP-SMX prophylaxis was well tolerated; most reactions were mild and self-limited and did not recur with re-institution of the drug . Only 6.1% of this cohort had TMP-SMX prophylaxis discontinued due to perceived toxicity . These data show that the currently recommended dose of TMP-SMX (150 mg/m2) may not be required to prevent PCP in children with HIV/AIDS . The drug is well tolerated at all dosage levels . The incidence of serious bacterial infection in this cohort of patients did not depend upon the amount of TMP-SMX prescribed . A prospective, controlled clinical trial of low-dose TMP-SMX for children with HIV infection is warranted. Eur Respir J, 2001 Aug, 18(2), 362 - 8 A prospective comparison of nursing home acquired pneumonia with community acquired pneumonia; Lim WS et al.; Nursing home acquired pneumonia (NHAP) is thought to be clinically distinct from community acquired pneumonia (CAP) . This observation, based on studies conducted mainly in North America, may not be relevant in countries with a different healthcare system . The authors describe an 18-month prospective cohort study of 437 patients admitted to hospital with CAP, 40 (9%) of whom came from nursing homes . Detailed microbiological tests were performed in a subset of patients over 12 months . Patients with NHAP were less likely to have a productive cough (odds ratio (OR) 0.4, p=0.02) or pleuritic pain (OR 0.1, p=0.03), but they were more likely to be confused (OR 2.6, p<0.001) . They had poorer functional status (p<0.001) and more severe disease (p=0.03) . Mortality was higher compared to CAP (53% versus 13%), but this was mainly explained by prior functional status (OR 0.5, after adjustment for functional status) . Pathogens were identified in 68% of 22 NHAP and 80% of 44 matched CAP patients . Streptococcus pneumoniae was the most common (55% NHAP, 43% CAP) . Atypical pathogens, enteric Gram negative bacilli and Staphylococcus aureus were uncommon . In conclusion, differences in functional status accounted for the increased mortality in nursing home acquired pneumonia compared to community acquired pneumonia . The pathogens implicated were similar . No grounds for a difference in choice of empirical antibiotics were apparent. J Biol Chem, 2001 Nov 2, 276(44), 41407 - 16 Epub 2001 Aug 29. Hyaluronan binding and degradation by Streptococcus agalactiae hyaluronate lyase; Li S et al.; Streptococcus agalactiae hyaluronate lyase is a virulence factor that helps this pathogen to break through the biophysical barrier of the host tissues by the enzymatic degradation of hyaluronan and certain chondroitin sulfates at beta-1,4 glycosidic linkages . Crystal structures of the native enzyme and the enzyme-product complex were determined at 2.1- and 2.2-A resolutions, respectively . An elongated cleft transversing the middle of the molecule has been identified as the substrate-binding place . Two product molecules of hyaluronan degradation were observed bound to the cleft . The enzyme catalytic site was identified to comprise three residues: His(479), Tyr(488), and Asn(429) . The highly positively charged cleft facilitates the binding of the negatively charged polymeric substrate chain . The matching between the aromatic patch of the enzyme and the hydrophobic patch of the substrate chain anchors the substrate chain into degradation position . A pair of proton exchanges between the enzyme and the substrate results in the cleavage of the beta-1,4 glycosidic linkage of the substrate chain and the unsaturation of the product . Phe(423) likely determines the size of the product at the product release side of the catalytic region . Hyaluronan chain is processively degraded from the reducing end toward the nonreducing end . The unsulfated or 6-sulfated regions of chondroitin sulfate can also be degraded in the same manner as hyaluronan. J Clin Microbiol, 2001 Sep, 39(9), 3316 - 20 Pneumococcal carriage in children in The Netherlands: a molecular epidemiological study; Bogaert D et al.; In 1999, Engelen and coworkers investigated colonization in Amsterdam among 259 children attending 16 day-care centers (DCCs) and among 276 children who did not attend day-care centers (NDCCs) . A 1.6- to 3.4-fold increased risk for nasopharyngeal colonization was observed in children attending DCCs compared with NDCC children, while no difference in antibiotic resistance was found between groups . The serotype and genotype distributions of 305 nasopharyngeal Streptococcus pneumoniae isolates of the latter study were investigated . The predominant serotypes in both the DCC and the NDCC groups included 19F (19 and 18%, respectively), 6B (14 and 16%, respectively), 6A (13 and 7%, respectively), 23F (9 and 7%, respectively), and 9V (7 and 7%, respectively) . The theoretical vaccine coverage of the 7-valent conjugate vaccine was 59% for the DCC children and 56% for the NDCC group . Genetic analysis of the pneumococcal isolates revealed 75% clustering among pneumococci isolated from DCC attendees versus 50% among the NDCC children . The average pneumococcal cluster size in the DCC group was 3.8 and 4.6 isolates for two respective sample dates (range, 2 to 13 isolates per cluster), while the average cluster size for the NDCC group was 3.0 (range, 2 to 6 isolates per cluster) . Similar to observations made in other countries, these results indicate a higher risk for horizontal spread of pneumococci in Dutch DCCs than in the general population . This study emphasizes the importance of molecular epidemiological monitoring before, during, and after implementation of pneumococcal conjugate vaccination in national vaccination programs for children. J Clin Microbiol, 2001 Sep, 39(9), 3290 - 5 Genetic and phenotypic features of Streptococcus pyogenes strains isolated in Brazil that harbor new emm sequences; Teixeira LM et al.; In the present study, 37 group A Streptococcus (GAS) strains belonging to 13 new emm sequence types identified among GAS strains randomly isolated in Brazil were characterized by using phenotypic and genotypic methods . The new types were designated st204, st211, st213, st809, st833, st854, st2904, st2911, st2917, st2926, st3757, st3765, and st6735 . All isolates were susceptible to the antimicrobial agents tested, except to tetracycline . They all carried the speB gene, and 94.6% produced detectable SpeB . Most strains belonging to a given emm type had similar or highly related pulsed-field gel electrophoresis profiles that were distinct from profiles of strains of another type . The other characteristics were variable from isolate to isolate, although some associations were consistently found within some emm types . Unlike the other isolates, all type st213 isolates were speA positive and produced SpeA . Strains belonging to st3765 were T6 and opacity factor (OF) negative . Individual isolates within OF-positive emm types were associated with unique s