|
|
|
|
|
| Microb Pathog, 2002 Apr, 32(4), 191 - 204 Streptococcus anginosus adheres to vascular endothelium basement membrane and purified extracellular matrix proteins; Allen BL et al.; The mechanisms of bacterial adherence in the initial stages of native valve endocarditis are unclear, especially in patients without valve disease or the presence of a platelet-fibrin thrombus . Extracellular matrix may act as a ligand in areas of exposed basement membrane on the endothelial monolayer . In this study, adherence of 55 clinical blood and 21 oral viridans streptococcal isolates was examined using purified extracellular matrix compounds . The majority of blood and oral isolates exhibited adherence to purified laminin, fibronectin, and fibrinogen, with lesser adherence to type I and IV collagens . Adherence to laminin and fibronectin was concentration dependent, saturable, and competitively inhibited with soluble ligand . A Streptococcus anginosus isolate and other viridans strains exhibiting a strong laminin adherence phenotype bound extensively to the endothelial aspect of human and porcine valve tissue sections and were inhibited by soluble laminin and anti-laminin antibody fragments . Using a novel native porcine valve explant adherence model, we localized binding to areas of exposed basement membrane by confocal and scanning electron microscopy . These studies support the hypothesis that bacterial adherence to exposed basement membrane plays a role in the initial phase of native valve endocarditis . Chang Gung Med J, 2002 Apr, 25(4), 266 - 70 Oral wooden stick injury complicated by meningitis and brain abscess; Chang CJ et al.; Meningitis is rarely seen following oral injury . We describe a 3-year-old boy developing meningitis and brain abscess following a penetrating oral wooden stick injury . There was no cerebrospinal fluid rhinorrhea noted . A cerebrospinal fluid culture yielded viridans streptococcus . Brain magnetic resonance imaging and computed tomography revealed a multiloculated ring-enhancing mass . This patient underwent surgical drainage and completed 8-week antibiotic therapy . The patient demonstrated a late and dismal complication of a penetrating oral injury . At 2-year follow-up the patient was in good condition . A penetrating oral wooden stick inury should be regarded as potentially serious. Implant Dent, 2002, 11(2), 162 - 9 Crestal bone loss around submerged and exposed unloaded dental implants: a radiographic and microbiological descriptive study; Barboza EP et al.; The successful maintenance of crestal bone surrounding dental implants is imperative for long-term implant success . Crestal bone loss is reportedly related to stress . However, early perforation and partial exposure of the implant's covering device are a focus for plaque accumulation, which, if left untreated, may result in inflammation . The objective of this study was to evaluate the crestal bone levels adjacent to submerged and exposed unloaded dental implants during the initial healing phase . In addition, the microbiota around exposed implants were studied . Bilateral implants were placed in the mandible of 10 patients . In one quadrant, the implants were covered by the flap . In the other quadrant, the flap was sutured, leaving the cover screws completely exposed . Standardized periapical radiographs were obtained at implant placement and 4 months later . Radiographs were digitalized, aligned, and analyzed with a computer-assisted method . Cultures were obtained from exposed implant sites . All patients showed more crestal bone loss around exposed dental implants compared to submerged implants . Prevotella sp., Streptococcus beta-hemoliticus, and Fusobacterium sp . were the microorganisms identified in most of the sites . The exposure of the implant covering device created foci for bacterial plaque accumulation, which may have facilitated periimplant crestal bone loss . The initial healing phase follow-up may be critical for implant success. Hua Xi Kou Qiang Yi Xue Za Zhi, 1998 Feb, 16(1), 76 - 9 {Study on the adhesion of an endemic strain of Streptococcus mutans serotype C to acquired pellicle . II . Isolation and extraction of adhesins of an endemic strain of Streptococcus mutans serotype C}; Zhan L et al.; Surface proteins of S . mutans WD9463 A(c) were separated by DEAE-Sephadex A25 Chromatography and Sepharose C1-6B Chromatography . The adhesins were distinguished by bacterial adhesin inhibition experiment and were identified by PAGE, SDS-PAGE, IEP-PAGE, immunol diffusion test, GTF activity test and annalization of the sorts of amino acid . The results showed P1, two proteins with molecular weight of 117 kD and 127 kD and two proteins with GTF activity could inhibit the adhesion effectively . On the other hand, another kind of GTF could improve the adhesion of the strain . These indicated that S . mutans may be many kinds of adhesins. Hua Xi Kou Qiang Yi Xue Za Zhi, 1998 Feb, 16(1), 73 - 5 {Study on the adhesion of an endemic strain of Streptococcus mutans serotype C to acquired pellicle . I . A comparison of the methods to extract adhesins from Streptococcus mutans}; Zhan L et al.; The adhesins of S . mutans serotype c endemic strain WD9463A were extracted from culture superant by cold ethol precipitation, or were extracted from cell surface by 0.5 mol/L phosphate buffer, 6 mol/L urea or 2% SDS solution . The composition and adhesive activities of the extracts were compared by SDS-PAGE and bacterial adhesion inhibition experiments . The results showed that the protein composition of the four extracts were similar, and all extracts inhibited the adhesion of the endemic strain dramatically . It indicates that four methods can be used to extract adhesins of S . mutans, but extracting adhesins from culture superant is better than the others. FEMS Microbiol Lett, 2002 Jun 18, 212(1), 133 - 8 The membrane-associated F(0)F(1) ATPase is essential for the viability of Streptococcus pneumoniae; Ferrandiz MJ et al.; Genetic studies aimed at eliminating expression of the atp operon (F(0)F(1) H(+)-ATPase) of Streptococcus pneumoniae by genetic disruption of atpC, the first gene of the operon, with a chloramphenicol-resistance cassette were performed . Resistant transformants were obtained only when the recipient strain had a duplication of atpC, recombination occurring in such a way that transcription of the operon from its own promoter was allowed . These results imply that the atp operon is essential for the viability of the cells. Clin Ther, 2002 May, 24(5), 818 - 34 Length of hospital stay and cost of Staphylococcus and Streptococcus infections among hospitalized patients; Zhao SZ et al.; BACKGROUND: Staphylococcus (Staph) and Streptococcus (Strep) infections are important causes of morbidity and mortality worldwide . The economic burden of these infections is also significant, especially among hospitalized patients . OBJECTIVE: The aim of this study was to estimate length of hospital stay (LOS) and total payments for hospital admissions for patients with Staph or Strep infection as a first (primary) or second or higher (comorbid) diagnosis . METHODS: From the 1994-1997 MarketScan inpatient database, admissions with Staph (n = 2,042) or Strep (n = 1,401) infection (905 as primary and 2,538 as comorbid diagnosis) and 89,899 control admissions without a diagnosis of gram-positive infection were identified . Crude and category-specific mean LOS and anti-log mean total payments were compared between admissions with Staph or Strep infection and admissions without a diagnosis of any gram-positive infection within major diagnostic categories and principal surgical procedures (SPs) . RESULTS: For admissions with Staph or Strep infection as first (primary) diagnosis (n = 905), the mean LOS was 4.68 days (95% CI, 4.44-4.93) and 4.78 days (95% CI, 4.35-5.26), respectively . The mean total payments were $6,445 (95% CI, $6,045-$6,870) and $6,821 (95% CI, $6,149-$7,566), respectively . In contrast, the average LOS and total payment for the control group were 2.99 days (95% CI, 2.98-3.01) and $6,325 (95% CI, $6,284-$6,365) . For admissions with infection as the comorbid diagnosis (n = 2,538), mean LOS and total payment were 4 days longer and $6,000 higher for Staph infections and 1.2 days longer and $1,200 higher for Strep infections than the control group . Within each SP, LOS and total payments were substantially higher for patients with Staph and Strep infections . Conclusions: The results of this study indicate that infections with the pathogens Staph and Strep substantially increase LOS and total payments among hospitalized patients. Pediatr Infect Dis J, 2002 Apr, 21(4), 297 - 303 Comparison of two dosages of azithromycin for three days versus penicillin V for ten days in acute group A streptococcal tonsillopharyngitis; Cohen R et al.; BACKGROUND: Three-day, 10 mg/kg/day azithromycin (AZM) studies in pediatric acute group A streptococcal tonsillopharyngitis have shown contradictory bacteriologic results . This study investigates the efficacy and tolerability of two dosages of 3-day azithromycin (20 mg/kg/day and 10 mg/kg/day) compared with 10-day penicillin V . METHODS: This was a prospective, comparative, randomized, multicenter trial . Children were scheduled to return for visits at 14 days (main end point) and 1 month after the onset of treatment for clinical and bacteriologic assessment . Molecular tools were used to compare pre- and posttreatment group A beta-hemolytic Streptococcus (GABHS) isolates . RESULTS: Between November, 1997, and July, 1998, 501 patients (169 AZM 10 mg, 165 AZM 20 mg, 167 penicillin V) between 2 and 12 years old were enrolled; 500 were assessable for safety, 469 for intent to treat analysis and 420 for efficacy in the per protocol analysis . Before treatment 25 (7.9%) of 315 GABHS stains isolated from patients receiving AZM were resistant to this compound . On Day 14 pretreatment GABHS were eradicated from 78 (57.8%) of the 135 children receiving the AZM 10 mg regimen, 131 (94.2%) of the 139 receiving AZM 20 mg and 123 (84.2%) of the 146 taking penicillin . One month after the outset of treatment, bacteriologic relapses were observed in 40.5% (n = 30) of the children receiving AZM 10 mg, 14.8% (n = 18) of children taking AZM 20 mg and 13.2% (n = 15) of those treated with penicillin V . AZM 20 mg/kg/day was statistically superior to AZM 10 mg/kg/day microbiologically on Day 14 (P = 0.0001) and Day 30 (P = 0.0001) and clinically on Day 14 (P = 0.0035) . AZM 20 mg/kg/day was statistically equivalent both microbiologically and clinically to standard therapy with penicillin V at all endpoints . The incidence of treatment-related adverse events was similar in the two azithromycin groups {AZM 10 mg, 31 of 169 (18.3%); AZM 20 mg, 37 of 164 (23%)} but significantly higher than those observed in the penicillin V group {5 of 166 (3%); P < 0.0001} . Most treatment-related adverse events were gastrointestinal and of mild-to-moderate severity . Fourteen patients withdrew from the trial because of adverse events (1 in the penicillin V group, 7 in the AZM 10 mg group and 6 in the AZM 20 mg group) . CONCLUSION: This is the first study to demonstrate a daily dose-dependent difference in microbiologic efficacy of a regimen; 3-day AZM 20 mg/kg/day is a more effective regimen than 3-day AZM 10 mg/kg/day for pediatric GABHS tonsillopharyngitis. Pediatr Infect Dis J, 2002 Apr, 21(4), 278 - 82 Invasive pneumococcal infections in children with asplenia; Schutze GE et al.; BACKGROUND: Asplenia is associated with an increased risk of infections caused by Streptococcus pneumoniae . Overwhelming infection can be fulminate and lead to a fatal outcome . OBJECTIVE: To review the epidemiology and clinical course of invasive S . pneumoniae infections in children with asplenia before the release of the conjugate pneumococcal vaccine . METHODS: Children with S . pneumoniae infections from eight children's hospitals in the US were identified prospectively from September, 1993, to August, 1999 . Further demographic, medical and microbiologic information was gathered retrospectively from the charts of patients with asplenia . RESULTS: Twenty-two asplenic patients with 26 episodes of invasive S . pneumoniae were identified . This represents 1% of the 2,581 episodes of invasive S . pneumoniae infections identified in our study . Twelve had congenital asplenia (CA), and 10 had undergone surgical splenectomy . Nine of the patients with CA had associated complex congenital heart disease . The median age at first infection was 12.5 months for CA patients as compared with 69 months in children with surgical splenectomy (P < 0.001) . Seventy-five percent of those eligible had received the polysaccharide pneumococcal vaccine . The most common serotypes isolated were 6B (8), 23F (7), 18C (2) and 19A (2) . Antimicrobial prophylaxis had been prescribed for 82% of the study cohort . Clinical presentations of the 26 episodes included fever (22), shock (7), petechiae or purpura (7), disseminated intravascular coagulation (5) and respiratory distress (5) . Clinical illness included bacteremia alone (12), meningitis alone (8), bacteremia with otitis media-sinusitis (3), bacteremia with pneumonia (2) and meningitis with osteomyelitis (1) . Five of the 6 patients who died had meningitis . Three of the survivors (19%) had significant morbidity, and all of them had meningitis . Two patients had 2 episodes each, and 1 patient had 3 episodes . All but 1 of the multiple episodes was with a different serotype . Forty-six percent of isolates were nonsusceptible to penicillin, and 19% were nonsusceptible to ceftriaxone . There was no association between antimicrobial resistance and mortality . CONCLUSIONS: Invasive pneumococcal disease in patients with asplenia has a high mortality, especially in those with meningitis . Even though the new conjugate vaccine might increase protection, 19% of patients had disease caused by serotypes not included in the current heptavalent vaccine . Clinicians should continue to be aggressive in evaluating asplenic patients with unexplained fevers. Otolaryngol Head Neck Surg, 2002 May, 126(5), 490 - 8 A rat model of otitis media with effusion caused by eustachian tube obstruction with and without Streptococcus pneumoniae infection: methods and disease course; Piltcher OB et al.; OBJECTIVE: To describe the clinical and histopathologic progression of a rat model of otitis media with effusion caused by eustachian tube obstruction (ETO) with and without Streptococcus pneumoniae infection . METHODS: In 164 rats, the left, bony eustachian tube was approached via a ventral incision and obstructed with dental material . Then 108 rats were infected via an intrabullar injection with S pneumoniae . At 48 hours, the infected rats were treated for 5 days with ampicillin . All ears were evaluated by weekly otomicroscopy . On each of days 1, 2, 7, 21, 35, 56, and 112, four rats were killed for histologic study . All effusions were cultured for bacteria . RESULTS: Fourteen rats died of surgical complications; effusion resolved by 2 weeks in 9 rats . During the first few days, infected ears with ETO had bulging tympanic membranes, followed by tympanic membrane retraction, purulent effusion, and otorrhea (50%) over the next few weeks, whereas uninfected ears with ETO developed retraction and serous effusion during the same time frame . At later times, all ears with ETO presented with retraction and serous or serous-mucoid effusion . S pneumoniae was recovered only from the infected ears with ETO (days 1 and 2), with some colonization by nonpathogenic microorganisms observed equally in both groups of ears . Histology showed a typical acute inflammatory reaction in the challenged ears with ETO through day 14 and then a chronic inflammation for all ears with ETO . CONCLUSION: The experimental methods provoked reproducible pathologic signs similar to those for otitis media with effusion . Given the availability of rat-specific reagents, this model is well suited for studies of cytokine elaboration during disease pathogenesis. Eur J Clin Microbiol Infect Dis, 2002 May, 21(5), 389 - 92 Epub 2002 May 17. Streptococcus pneumoniae-infected aneurysm extending from a persistent lobar pneumonia: case report and review of the literature; Nijs A et al.; Presented here is the case of a 63-year-old patient with a Streptococcus pneumoniae-infected aneurysm extending from a persistent lobar pneumonia of the left lung into the thoracic aorta . The patient was successfully treated with surgery and high-dose penicillin, and he remained well at 6-month follow-up . A review of the English-language literature over the past 25 years revealed 22 cases of mycotic or infected aortic aneurysms due to Streptococcus pneumoniae; however, none of these cases resulted in a positive outcome for the patient . The characteristics of these cases are discussed. J Oral Rehabil, 2002 Jun, 29(6), 553 - 8 Antibacterial and physical properties of resin modified glass-ionomers combined with chlorhexidine; Sanders BJ et al.; The purpose of this study was to determine the effect on mechanical properties and antimicrobial activity of the addition of chlorhexidine (CHX) to a resin modified glass-ionomer (Photac-fil, ESPE, Norristown, PA, USA) . Chlorhexidine diacetate was combined with a resin modified glass-ionomer material at a concentration of 5% . The samples were tested for hardness, tensile strength and erosion at 24 h and 6-week intervals and for elution of CHX and antimicrobial activity weekly for 6 weeks . At 24 h there was no significant difference in hardness between the two groups, but at 6 weeks the resin modified glass-ionomer group was significantly harder than the CHX groups (P < 0.05) . The diametral tensile strength test indicated no difference between the control and CHX groups at 24 h or at 6 weeks . The jet erosion test demonstrated significantly less erosion with the CHX group at 24 h but at 6 weeks the CHX group showed significantly more erosion than the control group . The chemical assay data demonstrated a peak elution of CHX at week 1 with residual amounts at weeks 2 and 3 . The microbial data demonstrated that the CHX group had a significant reduction in Streptococcus mutans numbers for weeks 1-3, but after week 4 there was no difference between the glass-ionomer with and without CHX . The addition of CHX to resin modified glass-ionomer altered hardness and erosion of the resin-modified glass-ionomer, but because there are no material specifications, it is difficult to determine clinical implications . Chlorhexidine did significantly improve the antimicrobial effect of the glass-ionomer which was consistent with the chemical assay data . The results indicated that the addition of CHX to resin modified glass-ionomer material (Photac-fil) did not seriously degrade the physical properties during the time period tested and that the addition of CHX resulted in a greater reduction in S . mutans when compared with glass-ionomer alone. Antimicrob Agents Chemother, 2002 Jul, 46(7), 2269 - 72 Fluorescence assay for studying the ability of macrolides to induce production of ribosomal methylase; Clarebout G et al.; A screening assay to test the inducing capacity of macrolides by fusing the attenuator of the inducible erm(B) gene from Streptococcus pneumoniae HM28 with the gfpmut1 gene has been designed . Fluorescence was detected under UV light around disks impregnated with inducer macrolides (erythromycin or azithromycin) but not with noninducer ketolides . Induction could be quantified by fluorometry. J Microbiol Methods, 2002 Sep, 51(1), 111 - 8 Evaluation of gene-technological and conventional methods in the identification of Streptococcus pneumoniae; Kaijalainen T et al.; To find reliable methods able to identify the "difficult" Streptococcus pneumoniae isolates, an in-house polymerase chain reaction (PCR) for pneumolysin gene (Ply-PCR) and a commercial RNA hybridisation test (AccuProbe) were evaluated . Selected isolates of suspected pneumococci, sent for confirmation of identification and for serotyping, were classified into four groups based on their optochin sensitivity and capsule reaction . All isolates in Group 1, which consisted of 24 typical, optochin-sensitive, encapsulated pneumococcal strains, were positive in the Ply-PCR and AccuProbe tests . In Group 2, which consisted of 25 optochin-sensitive, but unencapsulated pneumococcal strains, all the isolates were positive in the Ply-PCR test, and 23 were positive in the AccuProbe test . In Group 3, which consisted of 15 atypical, optochin-resistant but encapsulated pneumococci, 12 of the isolates were positive in the Ply-PCR and 12 in the AccuProbe test, and 11 of these 12 strains were positive in both tests . In Group 4, which consisted of 36 equivocal optochin-resistant, unencapsulated isolates, 15 strains were positive in the Ply-PCR test and 8 strains in the AccuProbe test . As a conclusion, the Ply-PCR and AccuProbe tests identified similarly typical optochin-sensitive pneumococci, but gave partly controversial results about atypical pneumococci . Thus, they did not reliably help in the identification of suspected pneumococcal isolates lacking the conventional characteristics of pneumococcus. J Microbiol Methods, 2002 Sep, 51(1), 35 - 42 Flow cytometric evaluation of adhesion of Streptococcus pyogenes to epithelial cells; Sethman CR et al.; The precise roles of various surface molecules in the attachment of Streptococcus pyogenes to host epithelia are currently unclear . A flow cytometry assay that facilitates the analysis of the kinetics of S . pyogenes adhesion to epithelial cells was developed . Dose- and time-dependent adhesion isotherms with both buccal epithelial cells (BECs) and Hep-2 cells as substrata were obtained . Although binding equilibrium is reached within 2 h on both cell types, saturation of binding sites on BECs is not achieved within a wide range of experimental conditions . This indicates a high degree of non-specific attachment to that cell type . Since no rinsing step is necessary when using flow cytometry to analyze adhesion, low-affinity associations were observable . This was confirmed by determining bacterial desorption rates early and late in the adsorption process . Binding irregularities were also easily detected since the cytometer records and displays data for up to 10,000 epithelial cells per time point . It is proposed to use this methodology to assign roles to particular surface molecules/characteristics during distinct phases of adhesion. JAMA, 2002 Jun 19, 287(23), 3103 - 9 Changes in antibiotic prescribing for children after a community-wide campaign; Perz JF et al.; CONTEXT: Overuse of antibiotics has contributed to microbial resistance, compromising the treatment of bacterial infections . Very high levels (>50%) of antibiotic resistance among invasive Streptococcus pneumoniae have been documented in Knox County, Tennessee . OBJECTIVE: To determine the effectiveness of a community-wide intervention aimed at reducing inappropriate antibiotic use among children . DESIGN, SETTING, AND PARTICIPANTS: The Knox County Health Department led a multifaceted year-long campaign (May 1997 through April 1998) aimed at decreasing unnecessary antibiotic use among children . Tennessee's 3 other major urban counties (Shelby, Hamilton, and Davidson) did not conduct similar campaigns and served as controls . Evaluation included white and black children (aged <15 years) enrolled in Tennessee's Medicaid Managed Care Program in the 4 study counties, representing 36% of the study counties' children (464 200 person-years observed) . INTERVENTION: Educational efforts were directed toward health care practitioners (primarily via peer leader presentations) and to the parents of young children and the public (primarily via printed materials) . MAIN OUTCOME MEASURE: The intervention-attributable effect on antibiotic use, defined as the excess percentage change in oral antibiotic prescription rates in Knox County between the 12-month preintervention and postintervention periods, relative to that of control counties . RESULTS: Antibiotic prescription rates declined 19% and 8% among Knox County and control county children, respectively, yielding an 11% intervention-attributable decline (95% confidence interval, 8%-14%; P<.001) . The intervention-attributable decrease in prescription rates was greatest among children aged 1 to less than 5 years (among white children, 8% {P<.001}; among black children, 18% {P<.001}) . CONCLUSIONS: A community-wide educational intervention reduced antibiotic prescription levels among children in Knox County. Biomaterials, 2002 Jul, 23(14), 2835 - 40 Bacterial adhesion to titanium-oxy-nitride (TiNOX) coatings with different resistivities: a novel approach for the development of biomaterials; Koerner RJ et al.; In this study the quantitative adhesion of a strain of Staphylococcus epidermidis, Streptococcus mutans and Pseudomonas aeruginosa to and the ease of removal from different TiNOX coatings was investigated by means of a parallel plate flow chamber and in situ image analysis . Quality of adhesion was determined by counting bacteria which remained attached to the surface after exposure to an air-liquid interface . S . epidermidis and S . mutans showed a bipolar adhesion pattern with highest numbers of adhesion at low and high resistivity with lowest adhesions at a resistivity of 10(4) microohms cm . P . aeruginosa was the least adherent organism . These results indicate that the affinity of these three strains under the current experimental conditions is minimal for TiNOX coatings with a specific resistivity . TiNOX coatings with pre-adsorbed fibrinogen showed different numbers of S . epidermidis adhered to the different coatings . However, the affinity of this strain for fibrinogen-coated TiNOX remains low when the resistivity is around 10(4) microohms cm . This indicates that the specific influence of the resistivities of the TiNOX coatings is transferred through the adsorbed fibrinogen film to the interface with adhering bacteria. J Vet Med B Infect Dis Vet Public Health, 2002 May, 49(4), 185 - 7 Studies on Streptococcus agalactiae isolated from bovine mastitis in Indonesia; Estuningsih S et al.; All 83 bacterial strains isolated from seven farms in three areas of the island of Java in Indonesia investigated in the present study could be identified as Streptococcus agalactiae . Identification was performed by cultural, biochemical and serological properties and by polymerase chain reaction amplification of species-specific parts of the gene encoding the 16S rRNA, the 16S-23S rDNA intergenic spacer region and the CAMP factor (cfb) gene . All isolates were unpigmented . almost all of the isolates had the serotype pattern II/X . Despite these similarities a macrorestriction analysis of the chromosomal DNA of the bacteria revealed no significant homologies of the DNA-fingerprints of the S . agalactiae from the various areas . This last finding might possibly indicate that a single ancestral unpigmented serotype II/X S . agalactiae clone was responsible for the mastitis situation on Java and had evolved separately in the various farms and regions. Aust N Z J Obstet Gynaecol, 2002 May, 42(2), 182 - 6 Late antenatal carriage of group B Streptococcus by New Zealand women; Grimwood K et al.; OBJECTIVES: To determine in New Zealand women the prevalence of group B Streptococcus (GBS) carriage late in pregnancy and to identify GBS colonisation risk factors, antibiotic susceptibility and serotype distribution . DESIGN: Prospective, observational study . SETTING: Community and hospital antenatal clinics in Wellington and Auckland during 1998-1999 . SAMPLE: Convenience sample of 240 women between 35-37 weeks gestation . METHODS: Sociodemographic data, obstetric details and anogenital swabs were collected from each subject . Swabs were inoculated into selective media . GBS isolates underwent serotyping and antibiotic susceptibility testing . RESULTS: Two hundred and forty women (9% Maori, 11% Pacific) aged 15-41 years were recruited . Fifty-two (22%; 95% CI 17, 27) were colonised by GBS . Carriage was independently associated with younger age (59% < or = 30 years; adjusted OR 3.25; 95% CI 1.53, 6.95) and least social deprivation (57% NZ Dep 96 score +/- 3; adjusted OR 1.22; 95% CI 1.06,1.39) . All GBS isolates were penicillin-susceptible, but resistance to clindamycin (15%) and erythromycin (7.5%) was detected and associated with serotype V strains . Predominant serotypes were: III (29%), Ia (21%), Ib (20%) and V (20%) . CONCLUSIONS: Approximately 20% of New Zealand women carry GBS late in pregnancy, with young age a major risk factor . Increased risk in the socially advantaged, development of resistance to erythromycin and clindamycin, and emergence of new GBS serotypes are findings with important implications for prevention strategies requiring further confirmation. Scand J Infect Dis, 2002, 34(5), 323 - 6 Serum level of YKL-40 is elevated in patients with Streptococcus pneumoniae bacteremia and is associated with the outcome of the disease; Kronborg G et al.; YKL40 is secreted by activated macrophages and neutrophils . Elevated serum concentrations of YKL40 are found in patients with diseases characterized by inflammation or ongoing fibrosis . The aim of this study was to evaluate serum YKL-40 levels in patients with Streptococcus pneumoniae bacteremia and to correlate these levels with clinical findings and outcomes . YKL40 was determined by ELISA and 89 patients were included in the study . Serum YKL-40 levels were significantly higher in patients with S . pneumoniae bacteremia (median 342 microg/l; range 20-20,400 microg/l) than in age-matched healthy subjects (44 microg/l; 20-184; p < 0.001) . Serum YKL-40 levels were related to the severity of the infection, with significantly higher serum YKL-40 levels being observed in patients who needed hemodialysis (p < 0.001), pharmacological treatment of hypotension (p < 0.001) and mechanical ventilation (p = 0.003) compared to those in patients who did not need this supportive treatment . Nineteen patients died and these patients had significantly higher serum YKL-40 levels (980 microg/l; 88-20,400 microg/l) than those of survivors (256 microg/l; 20-9,100 microg/l; p < 0.001) . Serum YKL40 level was an independent prognostic factor of survival in logistic multivariate regression analysis (p = 0.002) . In conclusion, high serum levels of YKL40 indicated a poorer prognosis for patients with S . pneumoniae bacteremia. Res Microbiol, 2002 May, 153(4), 243 - 7 Construction of new unencapsulated (rough) strains of Streptococcus pneumoniae; Pearce BJ et al.; To construct rough strains of Streptococcus pneumoniae in which the capsule locus was completely deleted, a genetic cassette to be used as a donor DNA in transformation was developed . The cassette contained an aphIII gene, conferring kanamycin resistance, flanked by segments of dexB and aliA . Since, in all strains of S . pneumoniae the capsule locus is between dexB and aliA, the DNA segments of these two genes allow insertion of a 1354-bp DNA fragment containing aphIII into the pneumococcal chromosome, determining the deletion of the whole capsule locus . The capsule locus was deleted from the classic type 2 and type 3 Avery's strains, from R6 (whose complete genome sequence is released) and Rx1 (the two most commonly used transformation recipients), from a type 3 clinical strain and type 19F clinical isolate G54 (whose draft genome sequence is annotated) . The effect of capsule removal was tested in 4 isogenic pairs . In unencapsulated strains, growth rate increased up to 56% and transformation frequency increased up to 1075-fold . A correlation was observed between the increase in growth rate and an increase in transformation frequency. Chest, 2002 Jun, 121(6), 1776 - 81 Clinical presentation of community-acquired Chlamydia pneumoniae pneumonia in adults; Miyashita N et al.; STUDY OBJECTIVE: To investigate the clinical presentation of community-acquired Chlamydia pneumoniae pneumonia in adults . DESIGN: Prospective study . SETTING: Kawasaki Medical School Hospital, Kawasaki Medical School Kawasaki Hospital, and Kurashiki Daiichi Hospital in Japan . PARTICIPANTS: Forty patients with community-acquired pneumonia with C pneumoniae as the only pathogen identified admitted to three hospitals between April 1996 and March 2001 and their clinical presentations were compared to patients with Streptococcus pneumoniae and Mycoplasma pneumoniae pneumonia . MEASUREMENTS: The diagnosis of C pneumoniae infection was based on isolation and serologic testing of antibodies by the microimmunofluorescence test . RESULTS: The clinical presentations, except for shortness of breath, were similar for the three major etiologic agents . The mean temperature of C pneumoniae patients on hospital admission was 37.9 degrees C, which was lower than that of patients with S pneumoniae and M pneumoniae . The mean WBC count on hospital admission was lower in the patients with C pneumoniae (mean, 9,100/microL) than in those with S pneumoniae pneumonia but higher than in those with M pneumoniae pneumonia . No patients required respiratory support or admission to an ICU, and no deaths occurred among the C pneumoniae pneumonia patients . CONCLUSIONS: Our results indicate that C pneumoniae pneumonia as a single etiologic agent is mild and that the underlying conditions and clinical symptoms closely resemble those of S pneumoniae pneumonia . However, the physical examinations, laboratory findings, and prognostic factors of the C pneumoniae patients resembled those of patients with M pneumoniae pneumonia. Rev Med Interne, 2002 May, 23(5), 469 - 73 {Cerebral hemorrhage due to a ruptured mycotic aneurysm . Two cases}; le Bayon A et al.; INTRODUCTION: Cerebral hemorrhages due to rupture of mycotic aneurysms are rare but severe complications of infective endocarditis . We report two cases with a good outcome . EXEGESIS: The first patient presented with a parieto-occipital hematoma which occurred in the course of a relapsing infective endocarditis due to Streptococcus mitis . She fully recovered after neurosurgical treatment . In the second case, a right frontal hematoma revealed two mycotic aneurysms and an infective endocarditis due to Streptococcus gordonii . Motor weakness partially recovered after antibiotic therapy and angiography demonstrated complete resolution of aneurysms . CONCLUSION: Ruptured mycotic aneurysms are poor prognosis factors in infective endocarditis . Adapted antibiotic therapy is the first-intent treatment . Neurosurgery is indicated when hematomas are poorly tolerated and in cases requiring anticoagulant therapy. HNO, 2002 Apr, 50(4), 332 - 8 {Clinical aspects of abscess development in parotitis}; Thiede O et al.; OBJECTIVE: The purpose of this paper was to analyse parotideal abscesses on the basis of a larger number of patients . PATIENTS AND METHODS: The data of 36 patients (mean age 44 years) with a parotideal abscess was analysed . RESULTS: Ultrasound scan was always necessary to verify the diagnosis . The surgical drainage was done under myoelectric monitoring of the facial nerve . Only in 1 patient a temporary minor paralysis of the mandibular branch was noticed . The most common bacteria were Staph . aureus, Streptococcus, and Peptostreptococcus . In 2 cases a tuberculosis and in 2 children an atypical mycobacterial infection was discovered . In another patient a metastasis of a squamous cell carcinoma was found . CONCLUSIONS: In every patient with an acute swelling of the parotid region without consideration of age, number of leucocytes or a typical fluctuation, an ultrasound scan should be used . The surgical drainage of the abscess should be done under myoelectric monitoring (Cave: muscle relaxant) . In every case, a specimen for microbiological analysis (bacterial determination) and a biopsy (to exclude malignoma or atypical mycobacteria) are necessary . A peri- and post-operative therapy with a combination of aminopenicillin and clavulanic acid or with cephalosporine is recommended. Naturwissenschaften, 2002 Apr, 89(4), 137 - 46 A review on usnic acid, an interesting natural compound; Cocchietto M et al.; Lichens are a world-widespread consortium of fungal and photosynthetic partners . Usnic acid is one of the most common and abundant lichen metabolites, well known as an antibiotic, but also endowed with several other interesting properties . This review summarises the most relevant studies on usnic acid, focusing on a number of biological activities in different fields . On the basis of the existing literature, usnic acid seems to be an exclusive lichen product . No synthetic derivatives more effective than the natural form are known . Both the (+) and (-) enantiomers of usnic acid are effective against a large variety of Gram-positive (G+) bacterial strains, including strains from clinical isolates, irrespective of their resistant phenotype . Of particular relevance is the inhibition of growth of multi-resistant strains of Streptococcus aureus, enterococci and mycobacteria . The (+)-usnic acid enantiomer appears to be selective against Streptococcus mutans without inducing perturbing side effects on the oral saprophyte flora . On the other hand, the (-)-usnic acid enantiomer is a selective natural herbicide because of its blocking action against a specific key plant enzyme . Other recognised characteristics of usnic acid are ultraviolet absorption and preserving properties . The toxicology, the in vitro anti-inflammatory effects and the mechanism of action of usnic acid need to be investigated in greater detail in order to reach clinical trials and to allow further applications . Furthermore, more research is needed to make possible intensive lichen culture, in order to produce large quantities of lichen substances for pharmaceutical, cosmetic and agricultural purposes . Some biological aspects, i.e . the possible biological roles of usnic acid, are discussed. Acta Paediatr, 2002, 91(4), 391 - 8 Early prediction of neurological sequelae or death after bacterial meningitis; Oostenbrink R et al.; This study determined independent predictors of the occurrence of permanent neurological sequelae or death after childhood bacterial meningitis . Data were used from a large study on children (aged 1 mo to 15 y) initially presenting with meningeal irritation . A nested case-control study was performed on children with (n = 23) and without (n = 70) permanent neurological sequelae (hearing impairment, locomotor dysfunction, mental retardation or epilepsy) or death after bacterial meningitis . Predictors obtained from clinical evaluation and laboratory tests at presentation and during the clinical course were identified by multivariate logistic regression and receiver operating characteristic (ROC) curve analyses . The study population comprised 23 cases and 70 controls (52% boys, median age 2.8 y) . Independent predictors for an adverse outcome after bacterial meningitis were male gender, atypical convulsions in history, low body temperature at admission and the pathogen Streptococcus pneumoniae . The area under the ROC curve of this prediction rule was 0.87 (95% confidence interval: 0.78-0.96), which was not improved by adding other characteristics . A score including these independent predictors could classify patients into categories with increasing risk for an adverse outcome . Conclusion: Clinical characteristics available early in the clinical course, such as gender, atypical convulsions in history, low body temperature at admission and the pathogen, are predictive for the occurrence of permanent neurological sequelae or death after bacterial meningitis in childhood . The pathogen type, in particular, is the main prognostic determinant of childhood bacterial meningitis. Proc Natl Acad Sci U S A, 2002 Jun 25, 99(13), 8962 - 7 Epub 2002 Jun 11. Assembling the glycopeptide antibiotic scaffold: The biosynthesis of A47934 from Streptomyces toyocaensis NRRL15009; Pootoolal J et al.; The glycopeptide antibiotics vancomycin and teicoplanin are vital components of modern anti-infective chemotherapy exhibiting outstanding activity against Gram-positive pathogens including members of the genera Streptococcus, Staphylococcus, and Enterococcus . These antibiotics also provide fascinating examples of the chemical and associated biosynthetic complexity exploitable in the synthesis of natural products by actinomycetes group of bacteria . We report the sequencing and annotation of the biosynthetic gene cluster for the glycopeptide antibiotic from Streptomyces toyocaensis NRRL15009, the first complete sequence for a teicoplanin class glycopeptide . The cluster includes 34 ORFs encompassing 68 kb and includes all of the genes predicted to be required to synthesize and regulate its biosynthesis . The gene cluster also contains ORFs encoding enzymes responsible for glycopeptide resistance . This role was confirmed by insertional inactivation of the d-Ala-d-lactate ligase, vanAst, which resulted in the predicted -sensitive phenotype and impaired antibiotic biosynthesis . These results provide increased understanding of the biosynthesis of these complex natural products. Int Endod J, 2002 Apr, 35(4), 345 - 51 Direct amplification of rRNA gene sequences for identification of selected oral pathogens in root canal infections; Siqueira JF et al.; AIM: The purpose of this study was to assess the prevalence of selected oral pathogens in root canal infections and their relationship with symptoms using a highly sensitive technique, the polymerase chain reaction . METHODOLOGY: Samples were obtained from 91 infected teeth associated with periradicular lesions, including cases of acute periradicular abscesses . DNA was extracted from the samples and analysed for the presence of target microbial species using a PCR-based identification assay . RESULTS: All samples were positive for the presence of bacteria . Streptococcus anginosus group was detected in 16.7%, Fusobacterium nucleatum in 14.3%, and Bacteroides forsythus in 7.1% of the abscess samples . No pus sample yielded Actinomyces israelii, Actinobacillus actinomycetemcomitans or fungal species . In general, B . forsythus was found in 20% of the cases (16 of 80), S . anginosus in 12% (6 of 50), F . nucleatum in 10% (6 of 60) and A . israelii in 5% (two of 40) . A . actinomycetemcomitans was not detected in any case . Fungi were present in only one of 50 cases (2%) . There was no correlation between the species and symptoms . CONCLUSIONS: Direct molecular approaches appear to be a valuable tool for the rapid and reliable diagnosis of infectious diseases, as well as for research purposes . There was no correlation between target microbial species and symptoms. Acta Anaesthesiol Scand, 2002 Jul, 46(6), 639 - 46 Post spinal meningitis and asepsis; Videira RL et al.; BACKGROUND: Post spinal meningitis (PSM) is a complication still currently being reported . After two PSM cases in our hospital an epidemiological study was initiated, which included a survey of techniques for asepsis that are applied in our department . METHODS: Cases defined as PSM comprised meningitis within a week after spinal anesthesia . Anesthesia records, anesthesia complication files and the records of the Hospital Commission for Infection Control from 1997 to 2000 were reviewed . Asepsis techniques applied were surveyed by a questionnaire answered by all our department's anesthesiologists . The equipment and procedures for spinal anesthesia were listed . Current anesthesia textbooks were reviewed for recommendations regarding asepsis techniques in conjunction with spinal anesthesia . RESULTS: Three cases of PSM were identified following 38,128 spinal anesthesias whereas none was observed in 12,822 patients subjected to other types of regional or general anesthesia (P>0.05) . Culture of cerebrospinal fluid yielded Streptococcus in two patients and was negative in the other patient . The asepsis technique applied by the anesthesiologists varied considerably . The literature review showed that aspects on asepsis for spinal anesthesia are poorly covered . CONCLUSION: The incidence of meningitis was similar in patients subjected to spinal anesthesia and in those subjected to other anesthetic techniques . Asepsis techniques were found to differ considerably among our staff members, reflecting the lack of well-defined published standards for this procedure . We recommend that asepsis for spinal anesthesia should not be less rigorous than for surgical asepsis. J Bacteriol, 2002 Jul, 184(13), 3508 - 20 Global transcriptional analysis of clpP mutations of type 2 Streptococcus pneumoniae and their effects on physiology and virulence; Robertson GT et al.; Streptococcus pneumoniae is an important human pathogen that contains single copies of genes encoding the ClpP and FtsH ATP-dependent proteases but lacks the Lon and HslV proteases . We constructed and characterized the phenotypes of clpP, clpC, and clpX deletion replacement mutants, which lack the ClpP protease subunit or the putative ClpC or ClpX ATPase specificity factor . A DeltaclpP mutant, but not a DeltaclpC or DeltaclpX mutant, of the virulent D39 type 2 strain of S . pneumoniae grew poorly at 30 degrees C and failed to grow at 40 degrees C . Despite this temperature sensitivity, transcription of the heat shock regulon determined by microarray analysis was induced in a DeltaclpP mutant, which was also more sensitive to oxidative stress by H2O2 and to puromycin than its clpP+ parent strain . A DeltaclpP mutant, but not a DeltaclpC mutant, was strongly attenuated for virulence in the murine lung and sepsis infection models . All of these phenotypes were complemented in a DeltaclpP/clpP+ merodiploid strain . Consistent with these complementation patterns, clpP was found to be in a monocistronic operon, whose transcription was induced about fivefold by heat shock in S . pneumoniae as determined by Northern and real-time reverse transcription-PCR analyses . Besides clpP, transcription of clpC, clpE, and clpL, but not clpX or ftsH, was induced by heat shock or entry into late exponential growth phase . Microarray analysis of DeltaclpP mutants showed a limited change in transcription pattern (approximately 80 genes) consistent with these phenotypes, including repression of genes involved in oxidative stress, metal ion transport, and virulence . In addition, transcription of the early and late competence regulon was induced in the DeltaclpP mutant, and competence gene expression and DNA uptake seemed to be constitutively induced throughout growth . Together, these results indicate that ClpP-mediated proteolysis plays a complex and central role in numerous pneumococcal stress responses, development of competence, and virulence. J Bacteriol, 2002 Jul, 184(13), 3426 - 32 Competence without a competence pheromone in a natural isolate of Streptococcus infantis; Ween O et al.; Many streptococcal species belonging to the mitis and anginosus phylogenetic groups are known to be naturally competent for genetic transformation . Induction of the competent state in these bacteria is regulated by a quorum-sensing mechanism consisting of a secreted peptide pheromone encoded by comC and a two-component regulatory system encoded by comDE . Here we report that a natural isolate of a mitis group streptococcus (Atu-4) is competent for genetic transformation even though it has lost the gene encoding the competence pheromone . In contrast to other strains, induction of competence in Atu-4 is not regulated by cell density, since highly diluted cultures of this strain are still competent . Interestingly, competence in the Atu-4 strain is lost if the gene encoding the response regulator ComE is disrupted, demonstrating that this component of the quorum-sensing apparatus is still needed for competence development . These results indicate that mutations in ComD or ComE have resulted in a gain-of-function phenotype that allows competence without a competence pheromone . A highly similar strain lacking comC was isolated independently from another individual, suggesting that strains with this phenotype are able to survive in nature in competition with wild-type strains. Curr Opin Microbiol, 2002 Jun, 5(3), 338 - 42 Streptococcus pneumoniae as a genomics platform for broad-spectrum antibiotic discovery; Glass JI et al.; Streptococcus pneumoniae is a useful tool for the discovery of broad-spectrum antibiotics because of its genetic malleability and importance as a pathogen . Recent publications of complete chromosomal DNA sequences for S . pneumoniae facilitate rapid and effective use of genomics-based technology to identify essential genes encoding new targets for antibacterial drugs . These methods include computational comparative genomics, gene disruption studies to determine essentiality or identify essential genes, and gene expression analysis using microarrays and gel-based proteomics . We review how genomics has transformed the use of the pneumococcus for the pursuit of new antibiotics, and made it the best species for the identification and validation of new antibiotic targets. Vaccine, 2002 Jun 7, 20(19-20), 2474 - 84 Development of a high-performance anion-exchange chromatography with pulsed-amperometric detection based quantification assay for pneumococcal polysaccharides and conjugates; Talaga P et al.; A method, using high-performance anion-exchange chromatography with pulsed-amperometric detection (HPAEC-PAD), has been developed to determine the concentrations of Streptococcus pneumoniae capsular polysaccharides and polysaccharide conjugates used in formulating a conjugate vaccine for the prevention of pneumococcal infections . In an effort to determine optimum hydrolysis conditions for the analysis, pneumococcal polysaccharides were subjected to three different hydrolysis methods: trifluoroacetic acid (TFA) hydrolysis, methanolysis followed by TFA hydrolysis, or hydrofluoric acid (HF) hydrolysis followed by TFA hydrolysis . For quantification purposes, best results were obtained by methanolysis followed by TFA hydrolysis for uronic acid-containing polysaccharides, and by TFA hydrolysis for all the others.For the quantification of all the polysaccharides (from native to conjugated forms), a monosaccharide reference mixture (Rha, Gal and GlcA) hydrolyzed along with the samples can be used as standards for routine analysis . This is much more convenient than to hydrolyze a well-characterized reference polysaccharide (necessary standard only for type 1 capsular polysaccharide).This method is rapid, very sensitive (less than 10 microg of polysaccharide is required), and may replace advantageously the currently used colorimetric assays used to determine polysaccharides content . Moreover, it can be readily adapted for use with other bacterial polysaccharide preparations as well. Stomatologiia (Mosk), 2002, 81(2), 40 - 4 {Clinical and laboratory studies of bacterial adhesion to validate the choice of material for making provisional dentures for patients with periodontal diseases}; Ibragimov TI et al.; Adhesion of bacteria favoring the development of oral inflammations, including cariesogenic and periodontopathogenic (Actinobacillus actinomycetemcommitans, Streptococcus sanguis, Fusobacterium nucleatum, Staphylococcus warneri) and yeast fungi (Candida albicans), to 13 materials used for making provisional dentures was studied . Adhesion of all the studied bacteria and fungi to Russian material Esterfil Foto was the minimum . Clinical use of this material in patients with chronic generalized periodontitis showed that it was well tolerated and the treatment led to improvement of oral microbiocenosis. Microbiology, 2002 Jun, 148(Pt 6), 1747 - 55 Organization and characterization of the capsule biosynthesis locus of Streptococcus pneumoniae serotype 9V; van Selm S et al.; The capsular polysaccharide (CPS) synthesis locus of Streptococcus pneumoniae serotype 9V was amplified by long-range PCR and sequenced . The locus was 17368 bp in size and contained 15 ORFs . The genetic organization of the cluster shared many features with other S . pneumoniae capsule loci, including the presence of four putative regulatory genes at the 5' end . Comparative sequence analyses allowed putative functions to be assigned to each of the gene products . The ORFs appeared to encode, besides the four regulatory genes, five glycosyltransferases, two O-acetyltransferases, an N-acetylglucosamine 2-epimerase, a glucose 6-dehydrogenase, an oligosaccharide transporter protein and a polysaccharide repeating unit polymerase . These functions covered the steps proposed in the CPS biosynthesis of serotype 9V . TLC of carbohydrate intermediates formed after incubation of bacterial membrane preparations with 14C-labelled precursors demonstrated that the fifth ORF (cps9vE) encoded a UDP-glucosyl-1-phosphate transferase . This function was confirmed with the help of a cps9vE mutant that carried a deletion of a guanine residue located adjacent to a stretch of adenines . The identification and characterization of the serotype 9V locus is a major step in unravelling the 9V capsule biosynthesis pathway and broadens the insight into the genetic diversity of the S . pneumoniae capsule loci. Microbiology, 2002 Jun, 148(Pt 6), 1615 - 25 Expression of fibronectin-binding protein FbpA modulates adhesion in Streptococcus gordonii; Christie J et al.; Fibronectin binding is considered to be an important virulence factor in streptococcal infections . Adhesion of the oral bacterium Streptococcus gordonii to immobilized forms of fibronectin is mediated, in part, by a high molecular mass wall-anchored protein designated CshA . In this study, a second fibronectin-binding protein of S . gordonii is described that has been designated as FbpA (62.7 kDa) . This protein, which is encoded by a gene located immediately downstream of the cshA gene, shows 85 and 81% identity to the fibronectin-binding proteins PavA, of Streptococcus pneumoniae, and FBP54, of Streptococcus pyogenes, respectively . Purified recombinant FbpA bound to immobilized human fibronectin in a dose-dependant manner, and isogenic mutants in which the fbpA gene was inactivated were impaired in their binding to fibronectin . This effect was apparent only for cells in the exponential phase of growth, and was associated with reduced surface hydrophobicity and the surface expression of CshA . Cells in the stationary phase of growth were unaffected in their ability to bind to fibronectin . By utilizing gene promoter fusions with cat (encoding chloramphenicol O-acetyltransferase), it was demonstrated that cshA expression was down-regulated during the exponential phase of growth in the fbpA mutant . Expression of fbpA, but not cshA, was sensitive to atmospheric O2 levels, and was found to be up-regulated in the presence of elevated O2 levels . The results suggest that FbpA plays a regulatory role in the modulation of CshA expression and, thus, affects the adhesion of S . gordonii to fibronectin. J Immunol, 2002 Jun 15, 168(12), 6375 - 81 Protection from Streptococcus pneumoniae infection by C-reactive protein and natural antibody requires complement but not Fc gamma receptors; Mold C et al.; Streptococcus pneumoniae is an important human pathogen and the most common cause of community-acquired pneumonia . Both adaptive and innate immune mechanisms provide protection from infection . Innate immunity to S . pneumoniae in mice is mediated by naturally occurring anti-phosphocholine (PC) Abs and complement . The human acute-phase reactant C-reactive protein (CRP) also protects mice from lethal S . pneumoniae infection . CRP and anti-PC Ab share the ability to bind to PC on the cell wall C-polysaccharide of S . pneumoniae and to activate complement . CRP and IgG anti-PC also bind to Fc gamma R . In this study, Fc gamma R- and complement-deficient mice were used to compare the mechanisms of protection conferred by CRP and anti-PC Ab . Injection of CRP protected wild-type, FcR gamma-chain-, Fc gamma RIIb-, and Fc gamma RIII-deficient mice from infection . Complement was required for the protective effect of CRP as cobra venom factor treatment eliminated the effect of CRP in both gamma-chain-deficient and wild-type mice, and CRP failed to protect C3- or C4-deficient mice from infection . Unexpectedly, gamma-chain-deficient mice were extremely sensitive to pneumococcal infection . This sensitivity was associated with low levels of natural anti-PC Ab . Gamma-chain-deficient mice immunized with nonencapsulated S . pneumoniae produced both IgM- and IgG PC-specific Abs, were protected from infection, and were able to clear the bacteria from the bloodstream . The protection provided by immunization was eliminated by complement depletion . The results show that in this model of systemic infection with highly virulent S . pneumoniae, protection from lethality by CRP and anti-PC Abs requires complement, but not Fc gamma R. Int J Syst Evol Microbiol, 2002 May, 52(Pt 3), 939 - 44 Isolation from a shea cake digester of a tannin-degrading Streptococcus gallolyticus strain that decarboxylates protocatechuic and hydroxycinnamic acids, and emendation of the species; Chamkha M et al.; A facultatively anaerobic, mesophilic, non-motile, non-sporulating bacterium, designated strain B7, was isolated from an anaerobic digester fed with shea cake rich in tannins and aromatic compounds, after enrichment on tannic acid . The coccoid cells (less than 2 microm in diameter) occurred in pairs or short chains and stained gram-positive . Strain B7 fermented a wide range of carbohydrates (cellobiose, fructose, galactose, glucose, lactose, maltose, mannitol, melibiose, raffinose and trehalose), grew optimally at pH 7.0 and had a G+C content of 40.4+/-0.3 mol% . Strain B7 was closely related to Streptococcus gallolyticus ACM 3611T, a member of the Streptococcus bovis rRNA cluster, with a sequence similarity of 98% and a DNA hybridization value of 86 mol% . Isolate B7 hydrolysed tannic acid and decarboxylated gallic acid to pyrogallol, traits also observed in S . gallolyticus ACM 3611T . In addition, both strains decarboxylated protocatechuic acid to catechol, p-coumaric acid to 4-vinylphenol, caffeic acid to 4-vinylcatechol and ferulic acid to 4-vinylguaiacol . An unsubstituted para-hydroxyl group on the benzene ring was required for decarboxylation . Glucose addition markedly increased the conversion rate . As these traits were not described previously, emendation of the description of the species Streptococcus gallolyticus is proposed. Vojnosanit Pregl, 2002 Mar-Apr, 59(2), 203 - 7 {Necrotizing fasciitis caused by group A streptococcus}; Mikic D et al.; The first case of the confirmed necrotizing fasciitis caused by Group A Streptococcus in Yugoslavia was presented . Male patient, aged 28, in good health, suddenly developed symptoms and signs of severe infective syndrome and intensive pain in the axillary region . Parenteral antibiotic, substitutional and supportive therapy was conducted along with the radical surgical excision of the necrotizing tissue . The patient did not develop streptococcal toxic shock syndrome thanks to the early established diagnosis and timely applied aggressive treatment . He was released from the hospital as completely cured two months after the admission. Obstet Gynecol, 2002 Jun, 99(6), 1036 - 9 Perianal versus anorectal specimens: is there a difference in Group B streptococcal detection? Orafu C, Gill P, Nelson K, Hecht B, Hopkins M. OBJECTIVE: To investigate whether specimens obtained from the perianal area have a Group B streptococcal culture detection rate similar to anorectal specimens . METHODS: This is a prospective cohort study at a tertiary care university-affiliated teaching hospital . A total of 136 pregnant women between 33 and 40 weeks' gestation were recruited . Three samples for Group B streptococcal culture detection were obtained from each subject in the following order: perianal sample, vaginoperianal sample, and an anorectal sample . The women were asked to rank their pain or discomfort with obtaining the anorectal sample . The vaginoperianal specimen is the standard sample obtained from antepartum patients in this clinic, and, therefore, it serves as the control . RESULTS: Of the 136 subjects, 26.5% of the control, vaginoperianal samples were positive for Group B streptococcal culture . In comparison, 27.2% of the anorectal specimens and 28.7% of the perianal specimens were positive for Group B streptococcal culture . There was no statistically significant difference in the detection of Group B streptococcal culture among the three sample sites . Evaluation of the pain experienced with an anorectal sampling showed that 68% of subjects ranked their pain between mild to moderate, and 5% noted severe pain . CONCLUSION: The Group B streptococcal detection rate was not different among the three sampling sites . Therefore, pregnant women do not need to be subjected to the additional pain of anorectal sampling to detect Group B Streptococcus. Vet Immunol Immunopathol, 2002 Aug, 87(1-2), 51 - 63 Changes in the leucocyte subpopulations of the palatine tonsillar crypt epithelium of pigs in response to Streptococcus suis type 2 infection; Salles MW et al.; The tonsils are portal of entry and a site of multiplication and persistence for a variety of pathogens, including Streptococcus suis (S . suis), which is a common cause of meningitis, septicemia and arthritis in pigs . Understanding the early changes that occur in the first barrier of the tonsil, i.e . the crypt epithelium, in response to S . suis infection is critical in clarifying the pathogenesis of this disease and for the future development of efficient methods of mucosal vaccination . In this study, we investigated the early changes, from 18 to 72 h, that occur in leucocyte subpopulations of the crypt epithelium of the palatine tonsils of 3-week-old pigs in response to S . suis type 2 infection . Monoclonal antibodies against leucocyte markers CD3, CD4, CD8, gammadelta T cell receptor, lambda-immunoglobulin light-chain, myeloid cells, and major histocompatibility complex class II molecule (MHC-II) were used in an avidin-biotin immunoperoxidase technique . An increase in the number of lambda-immunoglobulin light-chain positive cells (B cell subset) was noticed in crypts of S . suis-infected animals from 18 h after infection onwards . This increase was significant at 18 and 48 h after infection . The number of CD4 and CD8 cells was greater from 18 h onwards, with a significant increase at 24 and 72 h post-infection . No significant difference in numbers of CD3, gammadelta T cell receptor and MHC-II positive cells was detected in the crypts of infected animals compared to controls . Macrophages, neutrophils and crypt epithelial cells stained positively with the myeloid marker, and the area of crypt epithelium positive for this marker was increased in the crypts of infected animals, with a significant difference detected at 24 and 72 h after infection . These results suggest that there is participation of the innate immunity in the early phase of S . suis infection, represented by neutrophils, macrophages and likely epithelial cells, and that there is a potential for the initiation of both humoral and cellular responses against S . suis within the crypt epithelium of the palatine tonsil. J Biol Chem, 2002 Aug 30, 277(35), 32109 - 15 Epub 2002 Jun 05. Identification of the bacteria-binding peptide domain on salivary agglutinin (gp-340/DMBT1), a member of the scavenger receptor cysteine-rich superfamily; Bikker FJ et al.; Salivary agglutinin is encoded by DMBT1 and identical to gp-340, a member of the scavenger receptor cysteine-rich (SRCR) superfamily . Salivary agglutinin/DMBT1 is known for its Streptococcus mutans agglutinating properties . This 300-400 kDa glycoprotein is composed of conserved peptide motifs: 14 SRCR domains that are separated by SRCR-interspersed domains (SIDs), 2 CUB (C1r/C1s Uegf Bmp1) domains, and a zona pellucida domain . We have searched for the peptide domains of agglutinin/DMBT1 responsible for bacteria binding . Digestion with endoproteinase Lys-C resulted in a protein fragment containing exclusively SRCR and SID domains that binds to S . mutans . To define more closely the S . mutans-binding domain, consensus-based peptides of the SRCR domains and SIDs were designed and synthesized . Only one of the SRCR peptides, designated SRCRP2, and none of the SID peptides bound to S . mutans . Strikingly, this peptide was also able to induce agglutination of S . mutans and a number of other bacteria . The repeated presence of this peptide in the native molecule endows agglutinin/DMBT1 with a general bacterial binding feature with a multivalent character . Moreover, our studies demonstrate for the first time that the polymorphic SRCR domains of salivary agglutinin/DMBT1 mediate ligand interactions. Int J Pediatr Otorhinolaryngol, 2002 Jun 17, 64(2), 133 - 41 Deficient IgA and IgG2 anti-pneumococcal antibody levels and response to vaccination in otitis prone children; Dhooge IJ et al.; OBJECTIVE: To evaluate the isotype and IgG subclass distribution of anti-pneumococcal antibodies and response to polysaccharide vaccination in otitis prone children . METHODS: IgG1, IgG2 and IgA antibodies to pneumococcal serotypes 3, 4, 6B, 9V, 14, 19F and 23F were determined in otitis prone children and in an age-matched healthy control population . Patients were immunized with a 23-valent pneumococcal polysaccharide vaccine . The antibody response was measured 4 weeks later . RESULTS: Geometric mean IgA and IgG2 antibody levels for all seven pneumococcal serotypes tested were significantly lower in otitis prone children than in the control population . After immunization, there was no significant increase in geometric mean IgG2 anti-serotype 6B, 19F and 23F pneumococcal polysaccharide (weak immunogenic), but also no increase for IgG2 anti-serotype 4 and 14 . Post immunization IgG2 antibody titers for serotypes 6B, 9V and 19F even remained below titers of non-vaccinated controls . Nine out of 29 otitis prone children were colonized nasopharyngeally with Streptococcus pneumoniae during the time of vaccination; these children had an even more severely impaired systemic antibody response . CONCLUSIONS: Otitis prone children, while having normal IgG1 antibody levels, have low IgG2 and IgA anti-polysaccharide antibody levels and fail to respond in these subclasses upon vaccination with pneumococcal polysaccharide vaccine. Arch Otolaryngol Head Neck Surg, 2002 Jun, 128(6), 660 - 3 Suppurative complications of acute otitis media in the era of antibiotic resistance; Zapalac JS et al.; OBJECTIVE: To review our experience with suppurative complications of acute otitis media (AOM) in the era of antibiotic resistance, given a perceived increase in the number of such cases in recent years requiring surgical intervention . DESIGN: Retrospective review of pediatric patients presenting with suppurative complications of AOM from January 1993 to June 2000 . SETTING: Academic tertiary care children's medical center . PATIENTS: A total of 90 pediatric patients, ranging in age from 3 months to 16 years (mean age, 45 months) . RESULTS: A total of 104 suppurative complications of AOM occurred in 90 patients over the 7.5-year study period . The incidence of noncoalescent, coalescent, and total cases of mastoiditis and total number of suppurative complications all increased over the study period, with coalescent outpacing noncoalescent disease during the last 3 years of the study . A trend toward an increasing number of cases requiring surgical intervention was noted during the study period, corresponding to an increasing number of resistant Streptococcus pneumoniae isolates . Ten of 16 S pneumoniae isolates were resistant, primarily collected from younger children ranging in age from 4 to 24 months (mean age, 11.9 months) . CONCLUSION: The rising incidence of resistant S pneumoniae corresponded to the increasing number of suppurative complications of AOM during the study period and seemed to contribute to more aggressive infectious processes requiring surgical intervention. Lancet, 2002 May 4, 359(9317), 1569 - 73 MBL genotype and risk of invasive pneumococcal disease: a case-control study; Roy S et al.; BACKGROUND: Streptococcus pneumoniae is a major cause of morbidity and mortality in developed and developing countries . No common genetic determinants of susceptibility have been defined . Mannose-binding lectin (MBL) is a key mediator of innate host immunity that activates the complement pathway and directly opsonises some infectious pathogens . Mutations in three codons in the MBL gene have been identified, and individuals homozygous for a mutant genotype have very little or no serum MBL . We did a case-control study in the UK to assess whether these mutant genotypes were associated with invasive pneumococcal disease . METHODS: The frequencies of genotypes defined by the three mutations in codons 52, 54, and 57, and a functional promoter polymorphism at -221, were compared in a two-stage study of 337 patients with invasive pneumococcal disease and 1032 controls . All individuals were recruited from an ethnically homogeneous white population in Oxfordshire, UK . Patients had S pneumoniae isolated from a normally sterile site . FINDINGS: In our initial set of participants, 28 (12%) of 229 patients and 18 (5%) of 353 controls were homozygotes for MBL codon variants (odds ratio 2.59 {95% CI 1.39-4.83}, p=0.002) . Neither heterozygosity for these codon variants nor the promoter polymorphism was associated with susceptibility . In a confirmatory study, 11 (10%) of 108 patients were MBL homozygotes compared with 36 (5%) of 679 controls (p=0.046) . INTERPRETATION: Homozygotes for MBL codon variants, who represent about 5% of north Europeans and north Americans and larger proportions of populations in many developing countries, could be at substantially increased risk of invasive pneumococcal disease. J Paediatr Child Health, 2002 Jun, 38(3), 272 - 7 Early-onset neonatal group B streptococcal infections in New Zealand 1998-1999; Grimwood K et al.; OBJECTIVE: To determine in New Zealand infants the attack rates, risk factors, preventive policies, strain serotype and antibiotic susceptibilities of early-onset neonatal group B streptococcus (GBS) infection . METHOD: A 2-year prospective active surveillance study was conducted in New Zealand's 19 neonatal units . Cases had to present within 48 h of delivery, be unwell, possess abnormal haematological indices and have GBS isolated from sterile sites . RESULTS: Of the 112 402 infants born in New Zealand during 1998-1999, 56 had early-onset GBS infection, an attack rate of 0.5 per 1000 live births (95% confidence interval {CI} 0.38, 0.65) . Seven had meningitis and there was one death (case fatality rate of 1.8%; upper 95% CI 9.5%) . Univariate analysis identified young maternal age, parity, preterm labour, prolonged membrane rupture, maternal fever and assisted delivery as risk factors . Preventive policies for GBS were reported by 14 (74%) obstetric centres associated with neonatal units . Of the 56 cases, five (9%) were born to mothers receiving intrapartum antibiotics, 32 (57%) had mothers with risk factors but were not treated with antibiotics, and 19 (34%) were born to mothers without identifiable risk factors for GBS prevention . Serotypes Ia and III predominated, while two isolates were resistant to erythromycin and/or clindamycin . CONCLUSIONS: Rates of early-onset GBS infection are similar to other countries following the introduction of prevention policies . Further reductions are possible with full implementation of these guidelines . Meanwhile, emergence of antibiotic resistance complicates the management of women with penicillin allergy . Vaccine development therefore remains a priority. J Paediatr Child Health, 2002 Jun, 38(3), 246 - 51 Sepsis in neonatal intensive care in the late 1990s; Mehr SS et al.; AIM: To determine the incidence and clinical characteristics of sepsis in ventilated infants from an Australian neonatal intensive care unit (NICU) in the late 1990s . METHODS: Demographic data was collected from babies requiring assisted ventilation (AV) over the 6-month period from 1 July to 31 December 1998 . Sepsis was divided into early onset sepsis (EOS; " 72 h of age) and late onset sepsis (LOS; >72 h of age), including both definite (culture-proven + abnormal markers) and probable (culture negative + abnormal markers) episodes . RESULTS: Two hundred and eleven babies required AV over this period . Of these, 64 (30.3%) had at least one infection, with 85 episodes of sepsis (40.3 episodes per 100 admissions requiring AV) . There were 22 babies with 22 episodes of EOS, and 45 with 63 episodes of LOS . Three babies had both EOS and LOS . The rate of EOS was 10.4 infected infants (10.4 infections per 100 admissions requiring AV) . The rate of LOS was 21.3 infected infants (29.9 infections per 100 admissions requiring AV) . The rates of both EOS and LOS were higher than previously reported by Australian studies in the early 1990s . In both EOS and LOS, risk factors for infection were common . Group B streptococcus was the commonest cause of definite EOS . The mortality rate from sepsis in the EOS group was 14% (3/22) . Coagulase-negative staphylococci were the commonest cause of LOS . The mortality rate from sepsis in the LOS group was 11% (5/45) . CONCLUSIONS: EOS and LOS are significant problems in ventilated NICU infants in the late 1990s. Orbit, 2001 Sep, 20(3), 243 - 248 Orbital streptococcal gangrene and AIDS; Francis BA et al.; Streptococcal gangrene can present to the ophthalmologist as a fulminant orbital cellulitis involving the eyelids, globe and orbit . Compromised vision is likely, as well as serious systemic illness and death . It commonly affects young and healthy hosts and, prior to this presentation, has never been reported in a patient with HIV infection . We studied a case of streptococcal gangrene of the eyelids and orbit in a patient with AIDS . The infection was treated with debridement and intravenous antibiotics, and showed eventual improvement with the exception of visual function . A biopsy of the lesion exhibited extensive soft tissue necrosis with a predilection for blood vessels, resulting in thrombosis and infarction . Cultures grew out heavy group A beta-hemolytic Streptococcus . This case illustrates that streptococcal gangrene can occur with HIV, although to date this combination has been rare . Early diagnosis is crucial and includes recognition of incipient cutaneous, histopathological and anterior segment ischemia signs . FEBS Lett, 2002 Jun 5, 520(1-3), 68 - 72 Group B streptococcus (GBS) modifies macrophage phosphatidylserine metabolism during induction of apoptosis; Buratta S et al.; Group B streptococcus (GBS) induced macrophage apoptosis by which it could avoid host defence mechanisms . Macrophages, which constitutively express phosphatidylserine (PtdSer) on the outer leaflet of plasma membrane, increased PtdSer exposure during GBS-induced apoptosis . Induction of apoptosis decreased PtdSer radioactivity of macrophages incubated with {(3)H}serine . The effect appeared not due to increasing conversion of PtdSer to phosphatidylethanolamine or phosphatidylcholine nor to the release of radioactive membrane vesicles . The radioactivity in lysoPtdSer was also reduced . These results confirm that induction of apoptosis involves a modification of PtdSer metabolism and point out the typical features of the GBS-induced apoptosis with respect to other models of apoptosis. Int J Infect Dis, 2002 Mar, 6 Suppl 1, S38 - 46 Novel agents for resistant Gram-positive infections--a review; Strahilevitz J et al.; Gram-positive infections have increased in recent years, particularly those that are of nosocomial origin, leading to a broad use of agents with activity against these pathogens . Concomitantly, antimicrobial resistance of these pathogens also became widespread . Among the most common Gram-positive resistant pathogens are: Streptococcus pneumoniae, resistant to penicillin and macrolides, methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide-intermediately-resistant S . aureus (GISA), methicillin-resistant S . epidermidis, glycopeptide-resistant enterococci and vancomycin-resistant enterococci (VRE) . The response of the pharmaceutical industry to this challenge was the development of new antibiotics active against these pathogens . Among these antibiotics, this review will focus on: linezolid, an oxazolidinone; GAR-936, a tetracycline derivative; daptomycin, a lipopeptide; and ortivancin (LY-333328), a glycopeptide related to vancomycin . Except for linezolid, which has been recently launched in many countries, all other agents referred to in this review are still at various developmental stages . It is hoped that in the near future most of these agents will be approved and thus the grim outlook of patients infected with resistant Gram-positive bacteria may improve. Int J Infect Dis, 2002 Mar, 6 Suppl 1, S14 - 20 Penicillin-resistant pneumococci-implications for management of community-acquired pneumonia and meningitis; Ziglam HM et al.; Penicillin-nonsusceptible Streptococcus pneumoniae isolates have become increasingly prevalent worldwide . They are well-known agents of community-acquired infections such as otitis media, pneumonia and bacterial meningitis . Therapy of pneumococcal infections is made difficult by the emergence and spread of bacterial resistance to penicillin and other beta-lactams, as well as other antimicrobials such as macrolides . This article reviews current concepts of epidemiology and the implications of penicillin-nonsusceptible pneumococci for management of community-acquired pneumonia and meningitis. J Endod, 2002 Apr, 28(4), 279 - 82 An optimal host response to a bacterium may require the interaction of leukocytes and resident host cells; Jiang Y et al.; Bacterial infection results in inflammatory responses that may lead to soft-tissue damage and bone resorption . However, the mechanisms by which different bacteria contribute to lesions of endodontic origin are not fully understood . This study examined the response to Streptococcus mutans and Porphyromonas endodontalis in two cell types that are involved in periapical pathology, mononuclear and osteoblastic cells . This was accomplished by measuring the induction of chemokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-2) and proinflammatory cytokines (interleukin-1beta, tumor necrosis factor-alpha, interleukin-6, interferon-gamma) . The results demonstrated that S . mutans more efficiently stimulate inflammatory cytokine production by mononuclear cells, whereas P . endodontalis is relatively more potent in activating osteoblastic cells . Moreover, optimal activation of osteoblastic cells by S . mutans requires soluble mediators produced by mononuclear cells, whereas P . endodontalis does not . These results suggest that the association of different bacteria with specific pathologic processes may be partially explained by their capacities to activate specific host cells. Ugeskr Laeger . 2002 May 13;164(20):2629. {Bacteremia and meningitis caused by Streptococcus pneumoniae during treatment with azithromycin}; Lisby JG et al.; After absorption, azithromycin is concentrated intracellularly, with a correspondingly low serum concentration . A case of bacteriemia and meningitis caused by macrolide-sensitive Streptococcus pneumoniae during treatment with azithromycin is presented and discussed. Rev Med Chil, 2002 Mar, 130(3), 304 - 8 {In vitro susceptibility of streptococcus pneumoniae strains isolated from lower respiratory infections in Instituto Nacional del Tórax (INT)}; Soler T et al.; BACKGROUND: The rising antimicrobial resistance of streptococcus pneumoniae, requires permanent surveillance . Antimicrobial treatments of invasive infections must be modified accordingly . AIM: To assess the in vitro antimicrobial susceptibility of streptococcus pneumoniae strains isolated from lower respiratory infections . MATERIAL AND METHODS: Seventy five strains isolated during three periods in consecutive years were studied . In vitro susceptibility towards penicillin, erythromycin and ceftriaxone was studied using E-test technique minimal inhibitory concentrations . RESULTS: Five percent of strains were penicillin resistant and 11% had an intermediate sensitivity . Erythromycin resistance was observed in 1.3% of strains . Eight percent of strains had an intermediate sensitivity towards ceftriaxone and no resistance was observed . Comparing susceptibility in the three studied periods, it remained low and stable . CONCLUSIONS: High and intermediate resistance of Streptococcus pneumoniae towards penicillin is less prevalent than in other countries . A close surveillance must be maintained (Rev Med Chile 2002; 130: 304-8). Zh Mikrobiol Epidemiol Immunobiol, 2002 Mar-Apr, (2), 94 - 102 {Superantigens of Group A Streptococcus}; Danilova TA; In this review the superantigens (SAG) of group A Streptococcus, mainly pyrogenic toxins, and the coding genes are characterized . Specific sites on the molecules of the main histocompatibility complex, class II, and T-receptors, interacting with SAG, are described . This interaction results in hyperproduction of cytokines posing a systemic influence and leading to severe consequences . The data on the state of protective immunity in SAG-associated diseases and some approaches to their treatment are given. An Esp Pediatr, 2002 Jun, 56(6), 556 - 63 {Neonatal meningitis . Epidemiological study of the Grupo de Hospitales Castrillo}; Grupo de Hospitales Castrillo; OBJECTIVES: A prospective multicenter study was designed to assess the incidence, etiology, risk factors and outcomes of vertically transmitted and nosocomial meningitis in neonates over a two-year period . PATIENTS AND METHODS: Cases of neonatal meningitis diagnosed between January 1, 1997 and December 31, 1998 in the neonatology departments of 28 acute-care hospitals in Spain ("Grupo de Hospitales Castrillo") were prospectively studied . Bacteriological meningitis was considered confirmed when cerebrospinal fluid culture (CSF) was positive for bacteria, virus or fungi, probable when CSF culture was negative but blood culture was positive, and unconfirmed when both cultures were negative . RESULTS: During the study period, 151 cases of meningitis were diagnosed . Transmission was vertical in 84 cases and nosocomial in 67 . The incidence of vertically transmitted meningitis was 0.51 of live births, and was significantly higher in very low birth weight (VLBW) infants . Confirmed bacteriological meningitis was diagnosed in 66 patients (78.6 %) . No risk factors were identified in 46.4 % of the patients . Group B Streptococcus (agalactiae) was isolated in 48.5 % of cases of confirmed meningitis and Escherichia coli was isolated in 18.2 % . In 69.7 % of cases the results of blood culture were in agreement with those of CSF culture . The overall mortality rate was 8.3 %; mortality was significantly higher in VLBW infants (33.3 % vs 4.2 % in infants weighing 1,500 g) . Thirteen percent of survivors had sequelae.The incidence of meningitis of nosocomial transmission was 0.2 % of admissions and was more frequent in VLBW infants . Confirmed bacteriological meningitis was diagnosed in 49 patients (73.1 %) . Two or more risk factors were present in 62.7 % of patients . E . coli was isolated in 26.5 % of cases of nosocomial meningitis and Staphylococcus epidermidis was isolated in 24.5 % . In 55 % of patients the results of blood culture agreed with those of CSF culture . The overall mortality rate was 19.4 % . Mortality was significantly higher in VLBW infants and 18.5 % of survivors showed sequelae . CONCLUSIONS: The incidence, mortality and sequelae of neonatal meningitis in Spain were similar to those reported in recent studies . The most commonly isolated pathogens were group B Streptococcus in vertically transmitted meningitis and E . coli and S . epidermidis in nosocomial meningitis . We believe the distinction between vertical and nosocomial meningitis to be appropriate because the epidemiology of these diseases is different, which implies a different therapeutic approach . The high percentage of positive blood cultures indicates the need to include lumbar puncture whenever systemic infection is suspected in the neonatal period. J Chemother, 1991 Jan, 3 Suppl 1, 224 - 6 Efficacy and safety of teicoplanin in gram-positive pulmonary infections; Sanduzzi A et al.; Teicoplanin is a new antibiotic obtained from a culture filtrate of Actinoplanes teichomyceticus with potent activity against aerobic and anaerobic gram-positive bacteria and having a high affinity for healthy or inflamed bronchial mucosa and pulmonary parenchyma . To investigate the efficacy and safety of this drug, we selected 13 patients suffering from lower respiratory tract infections caused by gram-positive organisms . Pathogens isolated from sputum or bronchial aspirate were: 8 Staphylococcus aureus, 1 Staphylococcus epidermidis, 3 Streptococcus pneumoniae and 1 Streptococcus species . We began treatment as monotherapy at the dosage of 400 mg daily (200 mg x 2) I.M . only after microbiological evaluation . 11 patients (84.6%) were clinically and bacteriologically cured, 1 (7.7%) showed definite clinical improvement but persistence of causative agent and 1 (7.7%) failed to respond . The mean treatment period was 8.3 days . No major adverse effect was observed . We conclude that teicoplanin is a very efficacious and well-tolerated antibiotic for therapy of gram-positive pulmonary infections. J Chemother, 1991 Jan, 3 Suppl 1, 105 - 11 Antibiotics and expression of microbial virulence factors: implications for host defense; Gemmell CG; The discovery that antibiotics are capable of modifying both the structural appearance and physiology of pathogenic bacteria when they are incorporated in the culture medium at sub-growth inhibitory concentrations, has led to numerous examples in which the expression of one or more virulence factors (both structural and soluble) is inhibited or potentiated--some of these bacterial products are recognized in their own right as substances which can interfere with one or more stages of the normal process of phagocytosis viz, chemotaxis and Staphylococcus aureus alpha-toxin; opsonization and M protein of Streptococcus pyogenes; phagocytic ingestion and capsule of Bacteroides fragilis; phagocytic killing and streptolysin O of Streptococcus pyogenes . Exposure to these bacteria to low concentrations of various chemotherapeutic drugs can alter the efficacy of the phagocytic process . However, many examples exist in which no specific biochemical lesion induced by exposure to the antibiotic has been recognized . By way of contrast some recent experimental studies using genetically defined variants of S . aureus expressing protein A, alpha-toxin, beta-toxin or coagulase have allowed some discrimination as to the specifity of the drug action and the relative role of each virulence factor in bacterial pathogenicity . In particular it can be recognized that the presence or absence of protein A either through drug treatment (clindamycin or fusidic acid) or through gene delation is critical in determining bacterial susceptibility to opson-ophagocytosis . Extension of these studies to in vivo models will shed light on possible antibiotic-host defence interaction during chemotherapy. J Antimicrob Chemother, 2002 Jun, 49(6), 1015 - 8 Characterization of clinical Streptococcus pneumoniae strains from Germany with decreased susceptibility to fluoroquinolones; Reinert RR et al.; Fourteen pneumococcal strains isolated in three nationwide studies were characterized for amino acid changes in the enzymes GyrA, GyrB, ParC and ParE, and for the in vitro activity of eight fluoroquinolones and the new non-fluorinated quinolone BMS 284756 . Gemifloxacin and BMS 284756 exhibited the best in vitro activity against all 14 isolates tested . In nine of the 14 isolates mainly classical alterations in ParC (D83N/Y, S79Y/F), as well as rarer alterations such as S80P and D78N, contributed to the decreased susceptibility to fluoroquinolones . In two of the 14 isolates the classical alteration in GyrA (S81F) was found . In only one isolate did alterations in ParC and GyrA exist in parallel. J Antimicrob Chemother, 2002 Jun, 49(6), 935 - 9 Resistance to macrolides in clinical isolates of Streptococcus pyogenes due to ribosomal mutations; Malbruny B et al.; OBJECTIVE: Two clinical strains of Streptococcus pyogenes, 237 and 544, one isolated in Slovakia and the other in Croatia, that were resistant to azithromycin (MIC 8 and 2 mg/L, respectively) but susceptible to erythromycin (MIC 0.5 and 0.12 mg/L, respectively) did not contain any gene known to confer macrolide resistance by ribosomal modification (erm gene) or efflux {mef(A) and msr(A) genes} . The aim of the study was to determine the mechanisms of macrolide resistance in both strains . METHODS: Portions of genes encoding ribosomal proteins L22 and L4, and 23S rRNA (domains II and V) in the two macrolide-resistant strains and in control strains susceptible to macrolides, were analysed by PCR and single-strand conformational polymorphism, to screen for mutations . The DNA sequences of amplicons from resistant strains that differed from those of susceptible strains, in terms of their electrophoretic migration profiles, were determined . RESULTS: S . pyogenes 237 displayed a KG insertion after position 69 in ribosomal protein L4 . S . pyogenes 544 contained a C2611U mutation in domain V of 23S rRNA . CONCLUSION: Mutations at a similar position in ribosomal protein L4 and 23S rRNA have been reported previously in macrolide-resistant pneumococci . This report shows that similar mutations can be found in macrolide-resistant S . pyogenes. Med Pregl, 2002 Jan-Feb, 55(1-2), 41 - 3 {Bacteriologic study of the contents of radicular cysts}; Hrvacanin S; INTRODUCTION: Radicular cysts are, most often, oral tissue cysts . The basis for their development are the remains of Hertwig's epithelial sheath, which is stimulated to proliferate by infectious agents, mostly periapical granuloma or pulp necrosis . The cyst contents can be liquid, either clear or milky-white, or thick and yellowish-caseous pus . Bacteriological and histopathological researches have shown that development of radicular cysts from periapical lesions is a consequence of penetration of normal bacterial flora of the oral cavity . MATERIAL AND METHODS: The study has bacteriologically examined contents of 50 radicular cysts . They were operated between 1993 and 1995 at the Department of Oral Surgery of the Outpatient Health Care Centre Banja Luka . Pathological substrate of the cyst was punctured by a sterile needle and bacteriologically examined at the Microbiological Laboratory of the Clinical Centre in Banja Luka . DISCUSSION AND CONCLUSION: Radicular cysts contents most often consisted of: alpha-hemolytic streptococcus, Streptococcus pneumoniae, Staphyilococcus epidermidis, Streptococcus group B and alpha-hemolytic Streptococcus . It is concluded that normal oral cavity flora is present in the cysts contents, the infection penetrated through the root canal to periapex, where, due to the course of time, radicular cyst develops from periapical granuloma. Caries Res, 2002 Mar-Apr, 36(2), 116 - 21 Lactoperoxidase inhibits glucosyltransferases from Streptococcus mutans in vitro; Korpela A et al.; This study examines the possible effect of the antimicrobial peroxidase system on the activity of streptococcal glucosyltransferases B, C and D (GtfB, GtfC and GtfD), either in solution (GtfB and GtfC) or when adsorbed to hydroxyapatite (GtfC and GtfD) at pH 6.5 . The lactoperoxidase (LP) system (LP, H(2)O(2), SCN(-)) had no effect on the activity of dissolved GtfC, but the activity of dissolved GtfB was enhanced . The LP system, however, strongly inhibited the activities of both GtfC and GtfD in their adsorbed form . LP enzyme, without its substrates, inhibited all three Gtf enzymes: GtfB and GtfC in concentrations between 10 and 100 microg/ml in liquid phase and adsorbed GtfC and GtfD in concentrations between 25 and 50 microg/ml . This inhibition was in part abolished in liquid phase, but not in solid phase, if the substrates of LP were added . This study shows that the lactoperoxidase system can exert inhibitory activity against streptococcal Gtfs without generating oxidizing agents . Caries Res, 2002 Mar-Apr, 36(2), 101 - 7 Antibacterial activity of restorative dental biomaterials in vitro; Boeckh C et al.; This study investigated the antibacterial effects against Streptococcus mutans of a fine-hybrid resin composite (FH-RC; Tetric ceram), an ion-releasing resin composite (Ariston pHc), a self-curing glass ionomer cement (SC-GIC; Ketac-Molar), a resin-modified GIC (RM-GIC; Photac-Fil), and a zinc oxide eugenol cement (ZOE; IRM) . In a novel assay, bacterial suspensions were placed into narrow 20-microl conical cavities within the materials . After 0, 4, 8, 24, 48 h and 1 week of incubation, the suspensions were removed from the restoratives and the numbers of viable bacteria were determined . After incubation periods of 8 h or more, all restorative materials except the FH-RC showed significant growth inhibition when compared with controls . The strongest antibacterial activity was observed with ZOE . The inhibitory effect of Ariston pHc was similar to that of the SC-GIC and the RM-GIC . In the second assay, growth inhibition was evaluated in liquid cultures by incubating eluates of the materials with suspensions of S . mutans . Bacterial growth was determined up to 6 h by measuring absorption at 600 nm . The most marked inhibitory effect was again observed with ZOE . The SC-GIC caused a significant inhibition at all time intervals but the FH-RC, the RM-GIC and Ariston pHc exhibited no significant antibacterial effects . It is recommended to employ more than one method for assessing the antibacterial potential of restorative materials . Long-term clinical trials are necessary to determine whether the antimicrobial effects of dental materials are able to reduce the risk of secondary caries formation . J Clin Microbiol, 2002 Jun, 40(6), 2311 - 2 Fatal case of pneumonia caused by a nonhemolytic strain of Streptococcus pyogenes; Taylor MB et al.; We report a case of pneumonia with a fatal outcome caused by a nonhemolytic strain of Streptococcus pyogenes . This strain was isolated in pure growth from blood cultures and was fully identified biochemically . Such strains will be difficult to recognize and isolate from sites with heavy growth of normal flora . This phenomenon has been reported sporadically before, and it is unknown how common such strains may be in pharyngeal samples. Curr Treat Options Neurol, 2002 Jul, 4(4), 323 - 332 Central Nervous System Infections in the Immune-competent Adult; Smith TL et al.; The clinician must maintain a high level of suspicion for central nervous system infections even if not all of the classic signs are present, because prompt treatment may make a difference in patient outcome . If bacterial meningitis is suspected, a CT scan of the head should be obtained prior to lumbar puncture if there is papilledema, a focal neurologic exam, or if the patient is comatose . In bacterial meningitis, empiric antibiotics should be chosen based on a patient's risk factors and should be started immediately . Depending on the resistance patterns of the institution, Streptococcus pneumoniae may be resistant to penicillins and cephalosporins . Corticosteroids are of uncertain benefit in bacterial meningitis and may decrease the penetration of antibiotics into the central nervous system . The dosage for acyclovir treatment in herpes simplex encephalitis is 10 to 15mg/kg every 8 hours . Subdural empyema is a neurosurgical emergency . Brain abscesses should be surgically drained if they exceed 2.5 centimeters. Aust Dent J, 2002 Mar, 47(1), 21 - 6 Comparison of five selective media for the growth and enumeration of Streptococcus mutans; Wan AK et al.; BACKGROUND: Although a few growth media are available for selective isolation of the cariogenic bacteria, Streptococcus mutans (S . mutans), it is still unclear as to which is the most efficacious . This study compared the selectivity and sensitivity of five different media for growing a laboratory strain of S . mutans (NCTC 10449), and for enumerating S . mutans from teeth of a group of young children, aged 2-10 years . METHODS: The media tested in this study were mitis salivarius with bacitracin (MSB), mitis salivariuskanamycin-bacitracin (MSKB), glucose-sucrose-tellurite-bacitracin (GSTB), trypticase soy-sucrose-bacitracin (TYS20B) and tryptone-yeast-cysteine-sucrose-bacitracin (TYCSB) agars . These were prepared according to the respective manufacturer's instructions . RESULTS: The results showed that at concentrations of bacteria 1 x 10(3) to 1 x 10(10)/mL, the recovery of the laboratory S . mutans strain was highest in TYCSB agar, followed by in descending order by TYS20B, MSB, GSTB, and MSKB (p<0.01) . Similar results were obtained using dental plaque samples collected from swabs of the teeth of a group of children . In the clinical samples, TYCSB again showed the highest recovery rates of S . mutans compared to the other four media . Results were reproduced at dilutions of the samples at 1:20 x 10(6) to 1:2 x 10(6), and S . mutans concentrations of 1.6 to 7.7 Log 10 CFU/mL . In addition, there were highest ratios of mutans to non-mutans bacteria in TYCSB compared to the other media, suggesting high selectivity of this media for mutans species . CONCLUSION: The results of our study suggest that TYCSB is the most sensitive and selective media for culture of S . mutans for laboratory and clinical studies. Ann Fr Anesth Reanim, 2002 Apr, 21(4), 295 - 8 {Severe pneumococcal meningitis and ceftriaxone allergy}; Merat S et al.; We report the case of a 51-year-old man with an allergy to amoxicillin/acid clavulanique who presented with Streptococcus pneumoniae meningitis . Initial treatment consisted of an association of antibiotics including ceftriaxone . Six days after treatment was initiated the patient developed skin reaction and the diagnosis of allergy to ceftriaxone was established by the dosage of specific IgE . Typically Streptococcus pneumoniae meningitis is treated with vancomycin and a third-generation cephalosporin . This association had to be modified because cross allergy to cephalosporins could have developed in this patient who had previously reacted to penicillins. Clin Infect Dis, 2002 Jun 15, 34(12), 1613 - 20 Epub 2002 May 16. Resistance among Streptococcus pneumoniae: Implications for drug selection; Appelbaum PC; Streptococcus pneumoniae is an important pathogen in many community-acquired respiratory infections in the United States and a leading cause of morbidity and mortality worldwide . Unfortunately, S . pneumoniae is becoming increasingly resistant to a variety of antibiotics . Results of recent surveillance studies in the United States show that the prevalence of penicillin-nonsusceptible S . pneumoniae ranges from 25% to >50%, and rates of macrolide resistance among pneumococci are reported to be as high as 31% . A high prevalence of resistance to other antimicrobial classes is found among penicillin-resistant strains . Newer quinolones (e.g., gatifloxacin, gemifloxacin, and moxifloxacin) that have better antipneumococcal activity in vitro are the most active agents and therefore are attractive options for treatment of adults with community-acquired respiratory infections . Efforts should be made to prevent pneumococcal infections in high-risk patients through vaccination. Clin Infect Dis, 2002 Jun 15, 34(12), 1576 - 84 Epub 2002 May 24. Streptococcus agalactiae infective endocarditis: analysis of 30 cases and review of the literature, 1962-1998; Sambola A et al.; We describe 30 cases (1.7%) of community-acquired penicillin-susceptible Streptococcus agalactiae endocarditis among 1771 episodes of endocarditis diagnosed in 4 Spanish hospitals from 1975 through 1998 . Endocarditis affected a native valve (most often the mitral valve) in 25 cases (83%) . Surgical valve replacement was performed for 12 patients (40%) . Fourteen patients (47%) died . Mortality rates for patients with native and prosthetic valve endocarditis were 36% and 100%, respectively (P=.01) . The mortality rate for native valve endocarditis decreased during the last 6 years of the study (from 61% in 1975-1992 to 8% in 1993-1998; P<.05) . Additionally, 115 cases in the literature from 1962-1998 were reviewed . During 1980-1998, the percentage of patients who underwent cardiac surgery increased from 24% (in the previous period, 1962-1979) to 43% (P=.05) and the mortality rate decreased from 45% to 34% (P=NS) . S . agalactiae is an uncommon cause of endocarditis with a high mortality rate, although the prognosis of native valve endocarditis has improved in recent years, probably because of an increased use of cardiac surgery. Clin Infect Dis, 2002 Jun 15, 34(12), 1543 - 50 Epub 2002 May 21. Changes in antibiotic-prescribing practices and carriage of penicillin-resistant Streptococcus pneumoniae: A controlled intervention trial in rural Alaska; Hennessy TW et al.; From 1998 to 2000, 13 rural Alaskan villages (population, 3326) were surveyed annually by nasopharyngeal cultures for Streptococcus pneumoniae carriage . Data regarding antibiotic use for the entire population was abstracted from clinic records . In 1999, education of medical providers and the community about appropriate antibiotic use began in 4 villages; this program was expanded to include all villages in 2000 . Antibiotic courses per person decreased by 31% in the initial intervention villages and by 35% in the remaining villages after education (P<.01 for each) . Samples were obtained for culture from a mean of 31% of the population each year; 31% carried pneumococcus . No sustained decrease in carriage of penicillin-nonsusceptible strains was observed . When linear regression was used, serotype accounted for 81% of the variance in pneumococcal minimum inhibitory concentrations after the intervention, compared with 7% for antibiotic use . This suggests that reducing the carriage of serotypes associated with antibiotic resistance by use of pneumococcal conjugate vaccines may have a greater short-term impact than does decreasing antibiotic use. Panminerva Med, 2002 Jun, 44(2), 151 - 4 Pneumococcal septic arthritis of the shoulder . Case report and literature review; Bertone C et al.; Septic arthritis due to Streptococcus Pneumoniae appears to be relatively uncommon . Single- or clustered-case histories constitute the majority of reports on pneumococcal septic arthritis . A 70-year-old man presented with a 7-day history of pain, erythema and swelling of the left shoulder . Physical examination of the left shoulder revealed a warm, swollen, erythematous, and markedly tender to light palpation . The patient was unable to elevate his arm more than 30 degrees without pain . Arthrocentesis performed on admission produced 30 cc of grossly purulent fluid whose culture demonstrated S . Pneumoniae . The septic arthritis was treated with intravenous vancomycin and imipenem . The antibiotics were substituted when the sensitivities were known with oral ciprofloxacin and rifampycin to complete 8 weeks' total treatment . On follow-up examination 1 year later, the patient has remained afebrile and asymptomatic without evidence of increasing joint effusion or acute joint inflammation . Pneumococcal arthritis is classically described as a painful monoarticular arthritis complicating an active pneumococcal infection, generally a primary pulmonary infection . Pneumococcal arthritis appears to be predominantly a disease affecting the elderly . Clinical presentation ranges from septicemia to indolent infection with few systemic symptoms . With adequate antibiotic therapy and aspiration or drainage of the joint, the prognosis for return of normal joint function appears to be excellent . Although pneumococcal organisms are not likely causes, this bacteria should certainly be considered as a possible cause of arthritis or prosthetic infection. Proc Natl Acad Sci U S A, 2002 May 28, 99(11), 7646 - 51 Insight into the molecular basis of pathogen abundance: group A Streptococcus inhibitor of complement inhibits bacterial adherence and internalization into human cells; Hoe NP et al.; Streptococcal inhibitor of complement (Sic) is a secreted protein made predominantly by serotype M1 Group A Streptococcus (GAS), which contributes to persistence in the mammalian upper respiratory tract and epidemics of human disease . Unexpectedly, an isogenic sic-negative mutant adhered to human epithelial cells significantly better than the wild-type parental strain . Purified Sic inhibited the adherence of a sic negative serotype M1 mutant and of non-Sic-producing GAS strains to human epithelial cells . Sic was rapidly internalized by human epithelial cells, inducing cell flattening and loss of microvilli . Ezrin and moesin, human proteins that functionally link the cytoskeleton to the plasma membrane, were identified as Sic-binding proteins by affinity chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis . Sic colocalized with ezrin inside epithelial cells and bound to the F-actin-binding site region located in the carboxyl terminus of ezrin and moesin . Synthetic peptides corresponding to two regions of Sic had GAS adherence-inhibitory activity equivalent to mature Sic and inhibited binding of Sic to ezrin . In addition, the sic mutant was phagocytosed and killed by human polymorphonuclear leukocytes significantly better than the wild-type strain, and Sic colocalized with ezrin in discrete regions of polymorphonuclear leukocytes . The data suggest that binding of Sic to ezrin alters cellular processes critical for efficient GAS contact, internalization, and killing . Sic enhances bacterial survival by enabling the pathogen to avoid the intracellular environment . This process contributes to the abundance of M1 GAS in human infections and their ability to cause epidemics. Mol Pathol, 2002 Jun, 55(3), 182 - 5 Identification by 16S ribosomal RNA gene sequencing of Arcobacter butzleri bacteraemia in a patient with acute gangrenous appendicitis; Lau SK et al.; AIMS: To identify a strain of Gram negative facultative anaerobic curved bacillus, concomitantly isolated with Escherichia coli and Streptococcus milleri, from the blood culture of a 69 year old woman with acute gangrenous appendicitis . The literature on arcobacter bacteraemia and arcobacter infections associated with appendicitis was reviewed . METHODS: The isolate was phenotypically investigated by standard biochemical methods using conventional biochemical tests . Genotypically, the 16S ribosomal RNA (rRNA) gene of the bacterium was amplified by the polymerase chain reaction (PCR) and sequenced . The sequence of the PCR product was compared with known 16S rRNA gene sequences in the GenBank by multiple sequence alignment . Literature review was performed by MEDLINE search (1966-2000) . RESULTS: The bacterium grew on blood agar, chocolate agar, and MacConkey agar to sizes of 1 mm in diameter after 24 hours of incubation at 37 degrees C in 5% CO2 . It grew at 15 degrees C, 25 degrees C, and 37 degrees C; it also grew in a microaerophilic environment, and was cytochrome oxidase positive and motile, typically a member of the genus arcobacter . Furthermore, phenotypic testing showed that the biochemical profile of the isolate did not fit into the pattern of any of the known arcobacter species . 16S rRNA gene sequencing showed one to two base differences between the isolate and A butzleri, but 35 to 39 base differences between the isolate and A cryaerophilus, indicating that the isolate was a strain of A butzleri . Only three cases of arcobacter bacteraemia with detailed clinical characteristics were found in the English literature . The sources of the arcobacter species in the three cases were largely unknown, although the gastrointestinal tract is probably the portal of entry of the A butzleri isolated from the present case because the two concomitant isolates (E coli and S milleri) in the blood culture were common flora of the gastrointestinal tract . In addition, A butzleri has previously been isolated from the abdominal contents or peritoneal fluid of three patients with acute appendicitis . CONCLUSIONS: 16S rRNA gene sequencing was useful in the identification of the strain of A butzleri isolated from the blood culture of a patient with acute gangrenous appendicitis . Arcobacter bacteraemia is rare . Further studies using selective medium for the delineation of the association between A butzleri and acute appendicitis are warranted. J Microbiol Methods, 2002 Aug, 50(3), 313 - 8 Detection of Streptococcus pneumoniae DNA by using polymerase chain reaction and microwell hybridization with Europium-labelled probes; Rintamaki S et al.; The present paper describes a novel modification of polymerase chain reaction (PCR) for the detection of Streptococcus pneumoniae DNA in clinical specimens . PCR was based on the detection of a 209-base pair segment of the S . pneumoniae pneumolysin gene . For the demonstration of the amplification product, microwell hybridization with a Europium-labelled oligonucleotide probe complementary to a biotinylated strand of the PCR product was performed, and the presence of the PCR product was monitored by time-resolved fluorescence (TRF) of the Europium chelate . The sensitivity of the assay for purified S . pneumoniae DNA was 50 fg DNA corresponding to 20 genome equivalents of S . pneumoniae DNA . The efficiency of the hybridization step was monitored by using known amounts of synthetic target oligonucleotides as standards . Sensitivity of 3 x 10(8) molecules per individual reaction well was achieved with a 30-min attachment time and a 3-h hybridization time.Detection of PCR-amplified products by the microwell hybridization technique and TRF was compared to agarose gel electrophoresis in 50 middle ear fluid samples obtained from children with acute otitis media . The agarose gel and TRF detection methods identified all culture-positive samples, but both were also positive for 55% of the culture-negative samples . The results suggest that the detection of amplified PCR products by microwell hybridization using Europium-labelled oligonucleotides is a reliable method for the demonstration of the pneumolysin gene fragment . Furthermore, the method is suitable for automation and, thus, for testing high numbers of samples . The clinical significance of the PCR findings remains to be studied. Oral Microbiol Immunol, 2002 Jun, 17(3), 177 - 80 In vivo induction of proinflammatory cytokines in mouse tissue by Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans; Kesavalu L et al.; Periodontitis is a chronic inflammatory disease initiated by a multitude of bacteria . Persistent infection leads to generation of various inflammatory mediators, resulting in tissue destruction and osteoclastic resorption of the alveolar bone . This study describes a novel in vivo murine calvarial model to assess the effects of oral pathogens on the expression of three proinflammatory cytokines {interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha} which are involved in bone resorption . We chose Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans as prototype oral pathogens . We also tested the effects of Streptococcus gordonii, an oral commensal supragingival microorganism, considered a non-pathogen . Live bacteria were injected into subcutaneous tissue overlying the parietal bone of mice calvaria for 6 days . At the end of the experimental period, tissues overlying the calvaria were removed and analyzed for proinflammatory cytokine expression by Northern blotting . Cytokine mRNA was not detected in the tissue over the calvaria of control animals . In contrast, P . gingivalis and A . actinomycetemcomitans elicited mRNA expression of all three cytokines, TNFalpha being the highest (TNFalpha > > IL-1beta > IL-6) . P . gingivalis was more potent than A . actinomycetemcomitans in inducing cytokine expression . In contrast, S . gordonii induced only low levels of mRNA for IL-1beta and TNFalpha but no IL-6 mRNA induction . These results suggest that oral microorganisms with access to host tissues elicit a battery of proinflammatory cytokines . There were clear differences in profiles and, interestingly, a commensal bacterium also stimulated bone resorptive cytokine expression in host tissues. Oral Microbiol Immunol, 2002 Jun, 17(3), 163 - 71 Evaluation of interleukin 1 as a mucosal adjuvant in immunization with Streptococcus sobrinus cells by tonsillar application in rabbits; Kokuryo S et al.; To evaluate interleukin 1 (IL-1) as a mucosal adjuvant in the induction of salivary antibodies to Streptococcus sobrinus, S . sobrinus together with IL-1 was applied through the palatine tonsils of rabbits . IL-1 caused approximately 50 and 100% increases in the antibodies reacting against S . sobrinus fragments in the saliva and blood plasma, respectively, compared to the antibodies in those same fluids after tonsillar applications of S . sobrinus alone . In the case of the addition of IL-1, the antibodies reacting to the protein antigens of S . sobrinus increased in each fluid, without affecting the antibodies reacting to saccharide antigens . Delayed-type hypersensitivity to S . sobrinus, characterized by ear swelling and by an increase in IFN-gamma mRNA in RT-PCR analysis, was found to be induced only in rabbits immunized with IL-1 . S . sobrinus protein antigens caused ear swelling as intense as that caused by S . sobrinus fragments . Thus, IL-1 induced an antibody response and cell-mediated immunity mainly reacting to protein antigens of S . sobrinus. Acta Otolaryngol, 2002 Apr, 122(3), 255 - 61 Effect of 10 pharmacologic probes on mRNA levels of inducible nitric oxide synthetase and selected inflammatory cytokines in a rat model of acute otitis media; Hebda PA et al.; Ten drugs were screened for their ability to decrease inflammatory mediator (IL-6, inducible nitric oxide synthetase {iNOS}, IL-1beta and monocyte chemotactic protein {MCP-1}) expression in a rat model of acute otitis media caused by Streptococcus pneumoniae . Six adult rats were randomly assigned to each of 12 groups corresponding to uninfected controls and treatments with saline, aminoguanidine, anisomycin, dexamethasone, ketorolac, L-N(G)-nitroarginine methylester, methylprednisolone, mycophenolic acid, pentoxiphylline, tacrolimus or WEB2086 . Forty-eight h after the start of treatment, the ears of the animals in the 11 treatment groups were challenged with S . pneumoniae . Forty-eight h later, all animals were killed and middle ear mucosa was harvested and assayed for RNA message . Messages for IL-6, iNOS and MCP-1 were significantly increased as a result of infection . Most treatments decreased MCP-1 and four decreased IL-6 and iNOS . Tacrolimus and dexamethasone decreased IL-6, iNOS and MCP-1 . These results show that pharmacological agents can modify the expression of inflammatory mediators in this model and may have clinically relevant effects. Scand J Infect Dis, 2002, 34(3), 208 - 9 Mycotic aneurysm of the aorta caused by Group B Streptococcus; Andreasen DA et al.; We report a case of mycotic aneurysm of the abdominal aorta with Group B Streptococcus, a very rare cause of mycotic aneurysms . Following surgery the patient received 4 weeks of i.v . antibacterial chemotherapy . The patient remains asymptomatic after 9 months of follow-up. Kansenshogaku Zasshi, 2002 Apr, 76(4), 254 - 62 {Resistance to antimicrobiotics and mutation of PBPs in Streptococcus pneumoniae isolated from Kinki region of Japan}; Satoh K et al.; We studied the susceptibility to penicillin G (PCG) and other antimicrobiotics in 235 clinical isolates of Streptococcus pneumoniae . Samples were collected between April 1 and June 30, 2000 from nine medical institutions of the Kinki Region of Japan . We classified the minimum inhibitory concentration (MIC) of PCG according to the National Committee for Clinical Laboratory Standards (NCCLS) criteria . The overall rate of all types of S . pneumoniae resistance was 53.2% (penicillin-susceptible S . pneumoniae (PSSP): 46.8%, penicillin-intermediate S . pneumoniae (PISP): 42.6%, penicillin-resistant S . pneumoniae (PRSP): 10.6%) . In other antimicrobiotics, the resistance (R)/intermediate susceptibility (I) rates (R/I%) were as follows: ceftriaxone, 28.9%; cefotaxime, 7.7%; imipenem, 8.9%; meropenem, 9.8%; clarithromycin, 82.6%; clindamycin, 42.1%; levofloxacin, 0.4%; vancomycin, 0% . We used the polymerase chain reaction to study the mutations of the penicillin-binding proteins pbp1 a, pbp2b, and pbp2x in 140 strains of S . pneumoniae in the MIC for PCG was < 0.5 microgram/ml . Among the 109 strains of PSSP, 32 (29.4%) had no mutation and 77 (70.6%) showed mutation of more than one of the pbp mutations . Among the 31 strains of PISP, only 1 strain (3.2%) was not mutated . Since 70.6% of the strains classified as PSSP had pbp mutations, S . pneumoniae clearly can acquire resistance to anti-microbiotics . In the future, a comprehensive surveillance of S . pneumoniae is necessary. Kansenshogaku Zasshi, 2002 Apr, 76(4), 238 - 45 {M protein gene (emm) typing of Streptococcus pyogenes}; Katsukawa C et al.; T-agglutination typing and M protein gene (emm) typing were determined on the isolates of Streptococcus pyogenes taken from patients in Osaka and neighboring districts during 1996-2000 . A total of 701 isolates were classified to 15 kinds of T types and type untypable . In all isolates, T 12 was revealed as the most dominant serotype, followed by T1, T4 and T2 . The isolation rates of T 12 strains were high through these five years, and these of T1 or T4 strains formed epidemic waves showing the peak to be from 1997 to 1999 and 1998 to 2000, respectively . These of T2 strains were high in 1996 and 1997 and decreased rapidly . In 2000 T2 strain has not been detected . A total of 304 isolates were examined for emm typing . We are able to determine the emm type of all isolates including T-untypable (UT) isolates and to classify 21 kinds of emm types . T1, T2, T4, T6, T9, T11, T12, T22, T25 strains exhibited one T-type and emm type pattern association respectively such as T1/emm1, T2/emm2, T4/emm4, T6/emm6, T9/emm9, T11/emm11, T12/emm12, T22/emm22, T25/emm75 . Whereas T13 strains had varied T/emm pattern associations such as T13/emm73, T13/emm77, T13/emm101 . Similarly, T28, TB3264, UT had varied T/emm pattern associations . emm28 and emm87 were seen in T28, emm89 and emm94 in TB3264, emm2, emm12, emm22, emm58, emm75, emm77 and emm112 in UT . The emm typing method did not require many kinds of M typing antisera, and were successful by using the two highly conserved primers to amplify the emm gene and direct sequencing . Therefore, this method was a useful tool for typing Streptococcus pyogenes isolates. Curr Microbiol, 2002 Jul, 45(1), 13 - 7 Cloning and characterization of the deoxyribonuclease sd alpha gene from Streptococcus pyogenes; Hasegawa T et al.; The pathogenesis of Streptococcus pyogenes infection, especially toxic shock-like syndrome (TSLS), is still not fully understood; however, the exoproteins have been considered to play a role . We analyzed the culture supernatant proteins (exoproteins) from a TSLS-related isolate belonging to M3 serotype S . pyogenes by two-dimensional gel electrophoresis and characterized a single protein spot by using BLAST database . We cloned the gene of this protein and named it sd alpha, which was similar to the deoxyribonuclease (DNase) sdc of S . equisimilis . We showed that the recombinant protein from the sd alpha gene had DNase activity . By polymerase chain reaction, we found that the sd alpha gene was present in most clinically isolated S . pyogenes including TSLS-related isolates . We thus conclude that Sd alpha is a new DNase of S . pyogenes. Arch Microbiol, 2002 Jun, 177(6), 451 - 6 Epub 2002 Mar 23. Cloning and characterization of two novel DNases from Streptococcus pyogenes; Hasegawa T et al.; The proteins in the culture supernatant (exoproteins) from Streptococcus pyogenes serotype M1 were separated by two-dimensional gel electrophoresis, and their N-terminal amino acid sequences were determined . The amino acid sequences were compared to sequences in the S . pyogenes genome database . The coding sequence showed similarity to sequences of two genes, mf2-v ( mf2 variant) and mf3, which had sequence similarity to genes encoding mitogenic factor (MF); MF has DNase activity . The recombinant genes were expressed in Escherichia coli and the proteins were synthesized . Mf2-v and Mf3 had DNase activity . The activity of Mf2-v was localized to the C-terminal half of the protein . The mf3 gene was shown to be present in most clinically isolated strains of S . pyogenes tested, and the mf2gene was detected in 20% of the isolates . The products of the mf2 and mf3 genes in clinically isolated S . pyogenes strains were thus shown to be DNases. Emerg Infect Dis, 2002 Jun, 8(6), 594 - 7 Streptococcus pneumoniae, Brooklyn, New York: fluoroquinolone resistance at our doorstep; Quale J et al.; To examine the resistance rates and epidemiology of Streptococcus pneumoniae in Brooklyn, New York, isolates were collected during two boroughwide surveillance periods in 1997 and 1999 . Of 138 isolates, 67% were susceptible to penicillin and 34% to ciprofloxacin . Susceptibility rates to ciprofloxacin decreased dramatically from 1997 to 1999 (47% to 16%, p=0.0003) . Five isolates (3.6%) were resistant to levofloxacin . Western Brooklyn had lower rates of susceptibility to penicillin compared with eastern neighborhoods . More isolates in the eastern neighborhoods belonged to the Spanish/French 9/14 clone, and isolates in the western neighborhoods tended to belong to the Spanish/USA 23F clone . Residents of the western neighborhoods were more likely to be white and elderly and less likely to be receiving Medicaid or public assistance, characteristics associated with increased health-care and antibiotic use . Brooklyn residents appear to be at high risk for fluoroquinolone-resistant S . pneumoniae . Our results underscore the need for vigilant regional surveillance. J Immunol, 2002 Jun 1, 168(11), 5551 - 7 The mechanism underlying T cell help for induction of an antigen-specific in vivo humoral immune response to intact Streptococcus pneumoniae is dependent on the type of antigen; Wu ZQ et al.; Little is known concerning the role of T cells in regulating an anti-polysaccharide Ig response to an intact pathogen . We previously reported that the in vivo Ig responses to Streptococcus pneumoniae (strain R36A), specific for pneumococcal surface protein A (PspA) and for the phosphorylcholine (PC) determinant of C-polysaccharide, were both dependent on TCR-alphabeta(+) T cells and B7-dependent costimulation, although only PspA-specific memory was generated . In this report, we show that the T cell help underlying these two Ag-specific Ig responses is distinct . Using H-Y-specific T cell transgenic mice made "nonleaky" by crossing with mice genetically deficient for TCR-alpha, we demonstrate that the T cell help for the anti-PC, in contrast to the anti-PspA, response is TCR-nonspecific and occurs normally in the absence of germinal center formation, although it is still dependent on B7-dependent costimulation . Consistent with these data, we demonstrate, using cathepsin S(-/-) mice, that although the anti-PC response is largely dependent on CD4(+) T cells, there is a reduced (or lack of) dependence, relative to the anti-PspA response, on the generation of new peptide-MHC class II complexes . In this regard, the T cell help for an optimal anti-PC response is delivered more rapidly than that required for an optimal anti-PspA response . Collectively, these data demonstrate a novel accelerated TCR-nonspecific B7-dependent form of T cell help for augmenting a polysaccharide-specific Ig response to an intact bacterium without the generation of memory. Arch Dis Child, 2002 Jun, 86(6), 403 - 6 Invasive pneumococcal disease in England and Wales: what is the true burden and what is the potential for prevention using 7 valent pneumococcal conjugate vaccine? McIntosh ED, Booy R. BACKGROUND: The annual reported incidence rates for laboratory confirmed invasive pneumococcal disease (IPD) underestimate the true burden of invasive disease attributable to pneumococcal infection . AIMS: To estimate the proportion of "unspecified" mortality of infectious cause in infants and young children aged 1 month to 4 years reported by the Office for National Statistics (ONS) in England and Wales that could reasonably be attributed to IPD, thereby revising the total number of deaths per year potentially attributable to IPD, and producing a more accurate figure for the number of deaths that may be prevented by a programme of pneumococcal conjugate vaccination . METHODS: Polymerase chain reaction, latex agglutination, and other alternate methodologies to microbiological culture have been applied in various studies to the detection of Streptococcus pneumoniae . Some of these tests have been shown to be more sensitive indicators of pneumococcal infection . In our analysis the implications of these tests were applied theoretically to the "unspecified" clinical deaths caused by septicaemia, meningitis, and pneumonia reported by the ONS, with a 20% correction/reduction factor for nasopharyngeal carriage which these sensitive tests may coincidentally detect . RESULTS: The ONS reported an average of 13 deaths per year (1989-99) in infants and children aged 1 month to 4 years caused by pneumococcal septicaemia, meningitis, or pneumonia . By applying the rates for the more sensitive tests to the most recent ONS "unspecified" mortality data available (1999), the actual annual number of deaths caused by IPD in the age group 1 month to 4 years is shown to be at least as high as 43 . CONCLUSIONS: The mortality as a result of IPD in infants and young children may be at least three times the reported rate . The 7 valent pneumococcal conjugate vaccine may have the potential to prevent up to 26 (61%) of the IPD deaths per year in infants and young children in England and Wales alone. Antimicrob Agents Chemother, 2002 Jun, 46(6), 2046 - 8 Pharmacodynamics of moxifloxacin against Streptococcus pyogenes in an in vitro kinetic model; Odenholt I et al.; The aim of the present study was to investigate the pharmacodynamics of moxifloxacin against strains of Streptococcus pyogenes with different susceptibilities to erythromycin by using an in vitro kinetic model simulating human pharmacokinetics of moxifloxacin at oral doses of 400 and 200 mg, respectively . When the different strains of S . pyogenes were exposed to the higher dose, the number of bacteria was reduced below the detection limit after 12 h and no regrowth was noted during the following 12 h . At the lower dose there was regrowth of the strains with constitutive and inducible erythromycin resistance of the MLS(B) phenotype . Replication assays of the regrowing bacteria indicated that the failure of moxifloxacin to kill the MLS(B) strains at the lower dose was likely caused by the emergence of preexisting resistant subpopulations . Thus, the present study indicates that the presently used 400-mg dose seems to have an advantage over the lower dose in that the risk for selection of resistant subpopulations is minimized. Antimicrob Agents Chemother, 2002 Jun, 46(6), 1989 - 92 Determining Linezolid's baseline in vitro activity in Canada using gram-positive clinical isolates collected prior to its national release; Karlowsky JA et al.; All of the isolates of Staphylococcus aureus (n = 317), Enterococcus species (n = 315), Streptococcus pneumoniae (n = 282), and Staphylococcus epidermidis (n = 176) collected at 16 Canadian microbiology laboratories from October 2000 to April 2001 were susceptible to linezolid . Future studies will determine how linezolid clinical use in Canada affects its in vitro activity. Antimicrob Agents Chemother, 2002 Jun, 46(6), 1760 - 5 Evaluation of T-3811ME (BMS-284756), a new des-F(6)-quinolone, for treatment of meningitis caused by penicillin-resistant Streptococcus pneumoniae in rabbits; Takahata M et al.; T-3811ME (BMS-284756) is a new des-F(6)-quinolone with high levels of activity against gram-positive bacteria, including penicillin-resistant Streptococcus pneumoniae (PRSP) strains . T-3811, the free base of T-3811ME, exhibited potent activity against 28 clinical strains of PRSP isolated clinically (MIC at which 90% of the isolates tested are inhibited, 0.0625 microg/ml) . After the intravenous dosing of T-3811ME (20 mg/kg of body weight as T-3811) in rabbits with meningitis caused by PRSP, the area under the concentration-time curve (AUC) of T-3811 in cerebrospinal fluid (CSF) was 5.79 microg . h/ml and was 4.5-fold higher than that of T-3811in the CSF of rabbits without meningitis . In addition, the AUC/MIC for T-3811ME (20 mg/kg as T-3811) in CSF was 185, which was 4.3-fold higher than that for ceftriaxone (administered intravenously at 100 mg/kg) . After the administration of any dose of T-3811ME (5, 10, and 20 mg/kg as T-3811), the viable cell counts in CSF decreased in a dose-dependent manner . In particular, after dosing of 20 mg/kg (as T-3811), the viable cell counts in CSF were significantly less than those in the nontreated group (P < 0.01) . By histopathological evaluation, 6 h after the administration of T-3811ME (20 mg/kg as T-3811), the thickening of the cerebral meninx and the infiltration of neutrophils into the cerebral meninx were less severe in the treated group than in the nontreated group . T-3811ME (BMS-284756) may be expected to be evaluated for the management of meningitis caused by highly penicillin-resistant pneumococci. Antimicrob Agents Chemother, 2002 Jun, 46(6), 1680 - 7 Mefloquine and new related compounds target the F(0) complex of the F(0)F(1) H(+)-ATPase of Streptococcus pneumoniae; Martin-Galiano AJ et al.; The activities of mefloquine (MFL) and related compounds against previously characterized Streptococcus pneumoniae strains carrying defined amino acid substitutions in the c subunit of the F(0)F(1) H(+)-ATPase were studied . In addition, a series of MFL-resistant (Mfl(r)) strains were isolated and characterized . A good correlation was observed between inhibition of growth and inhibition of the membrane-associated F(0)F(1) H(+)-ATPase activity . MFL was about 10-fold more active than optochin and about 200-fold more active than quinine in inhibiting both the growth and the ATPase activities of laboratory pneumococcal strain R6 . Mutant strains were inhibited by the different compounds to different degrees, depending on their specific mutations in the c subunit . The resistant strains studied had point mutations that changed amino acid residues in either the c subunit or the a subunit of the F(0) complex . Changes in the c subunit were located in one of the two transmembrane alpha helices: residues M13, G14, G20, M23, and N24 of helix 1 and residues M44, G47, V48, A49, and V57 of helix 2 . Changes in the a subunit were also found in either of the transmembrane alpha helices, helix 5 or 6: residue L186 of helix 5 and residues W206, F209, and S214 of helix 6 . These results suggest that the transmembrane helices of the c and a subunits interact and that the mutated residues are important for the structure of the F(0) complex and proton translocation. Antimicrob Agents Chemother, 2002 Jun, 46(6), 1651 - 7 In vitro activities of novel nonfluorinated quinolones PGE 9262932 and PGE 9509924 against clinical isolates of Staphylococcus aureus and Streptococcus pneumoniae with defined mutations in DNA gyrase and topoisomerase IV; Jones ME et al.; Two 8-methoxy nonfluorinated quinolones (NFQs), PGE 9262932 and PGE 9509924, were tested against contemporary clinical isolates of Staphylococcus aureus (n = 122) and Streptococcus pneumoniae (n = 69) with genetically defined quinolone resistance-determining regions (QRDRs) . For S . aureus isolates with wild-type (WT) sequences at the QRDRs, the NFQs demonstrated activities 4- to 32-fold more potent (MICs at which 90% of isolates are inhibited {MIC(90)s}, 0.03 microg/ml) than those of moxifloxacin (MIC(90), 0.12 microg/ml), gatifloxacin (MIC(90), 0.25 microg/ml), levofloxacin (MIC(90), 0.25 microg/ml), and ciprofloxacin (MIC(90), 1 microg/ml) . Against S . pneumoniae isolates with WT sequences at gyrA and parC, the NFQs PGE 9262932 (MIC(90), 0.03 microg/ml) and PGE 9509924 (MIC(90), 0.12 microg/ml) were 8- to 64-fold and 2- to 16-fold more potent, respectively, than moxifloxacin (MIC(90), 0.25 microg/ml), gatifloxacin (MIC(90), 0.5 microg/ml), levofloxacin (MIC(90), 2 microg/ml), and ciprofloxacin (MIC(90), 2 microg/ml) . The MICs of all agents were elevated for S . aureus isolates with alterations in GyrA (Glu88Lys or Ser84Leu) and GrlA (Ser80Phe) and S . pneumoniae isolates with alterations in GyrA (Ser81Phe or Ser81Tyr) and ParC (Ser79Phe or Lys137Asn) . Fluoroquinolone MICs for S . aureus strains with double alterations in GyrA combined with double alterations in GrlA were > or =32 microg/ml, whereas the MICs of the NFQs for strains with these double alterations were 4 to 8 microg/ml . The PGE 9262932 and PGE 9509924 MICs for the S . pneumoniae isolates did not exceed 0.5 and 1 microg/ml, respectively, even for isolates with GyrA (Ser81Phe) and ParC (Ser79Phe) alterations, for which levofloxacin MICs were > 16 microg/ml . No difference in the frequency of selection of mutations (< 10(-8) at four times the MIC) in wild-type or first-step mutant isolates of S . aureus or S . pneumoniae was detected for the two NFQs . On the basis of their in vitro activities, these NFQ agents show potential for the treatment of infections caused by isolates resistant to currently available fluoroquinolones. MMWR Morb Mortal Wkly Rep, 2002 May 10, 51(18), 392 - 4 Assessment of susceptibility testing practices for Streptococcus pneumoniae--United States, February 2000; Invasive group A streptococcal infections in a large tertiary center: epidemiology et al.; Dept of Anesthesiology and Critical Care Medicine, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, IsraelBACKGROUND: Invasive group A streptococcal (GAS) infections are increasing alarmingly worldwide . PATIENTS AND METHODS: To determine the clinical and epidemiologic characteristics of invasive GAS in a large tertiary medical center, we retrospectively surveyed microbiology and medical records of patients with invasive GAS infections (isolation of Group A Streptococcus from a normally sterile site) treated in our hospital from January 1995 to December 1997 . RESULTS: 70 patients with a median age of 48 years (range 2 months-88 years) were identified . Of the 70 identified, 53 (76%) were adults (age > or = 19 years) . The most common co-morbid diseases for invasive GAS in adults were diabetes mellitus, congestive heart failure (CHF), malignancy and immunosuppression . A probable port of entry was identified in 31 (44%) of the cases . In children, varicella lesions were the major port of entry . Overall mortality rate was 17%: The difference in mortality between pediatric and adult cases was significant (0/17 vs 12/53, respectively; p = 0.03).Toxic shock syndrome (TSS) and necrotizing fasciitis were identified in 8.6% and 5.7% of the cases, respectively, with mortalities of 83.3% and 25% . Hyponatremia and hypocalcemia were more frequently observed among the severely ill . CONCLUSION: Invasive GAS infections tend to have an unexpected course and a broad clinical spectrum, ranging from local skin or pharyngeal involvement to deeply invasive fasciitis with TSS and high mortality . The elderly and those with underLying medical conditions are at utmost rsk for invasive GAS . Clear-cut guidelines for early therapeutic strategy, i.e . antibiotic administration and preemptive hospital admission are needed for community-based physicians. J Dairy Sci, 2002 Apr, 85(4), 1009 - 14 Effective treatment of Streptococcus uberis clinical mastitis to minimize the use of antibiotics; Hillerton JE et al.; Antibiotic regimens (intramammary antibiotic, penicillin-based parenteral treatment) and intramuscular oxytocin were tested for effectiveness against experimental infection by Streptococcus uberis with the following results from 54 animals: a) no treatment led to deterioration of infected quarters, requiring intervention within 48 h for cow health; b) aggressive intramammary antibiotic at every milking achieved 70% clinical cure in 3 d and 100% cure within 6 d; overall bacteriological cure was 80%; c) parenteral treatment alone used about 14 times as much antibiotic with 18% clinical cure in 3 d and 91% within 6 d; overall bacteriological cure was 80%; d) combination of aggressive intramammary and parenteral treatments achieved 61% clinical cure in 3 d and 100% within 6 d; overall bacteriological cure was 72%; e) intramammary antibiotic at labeled rates (1x for 3 d) achieved 27% clinical cure in 3 d but 91% within 6 d of treatment; overall bacteriological cure was 64%; f) use of oxytocin alone for 3 d failed to achieve clinical improvement with an increase in the severity of mastitis; g) combining oxytocin with labeled use of intramammary antibiotic (1x for 3 d) was unsuccessful: 0% clinical cures in 3 d, 10% in 6 d; significantly poorer than intramammary antibiotic alone . Extended treatment periods with parenteral or intramammary antibiotics resulted in positive inhibitory tests for milk from individual quarters up to 8 d after treatment . Aggressive intramammary antibiotic was the most effective treatment for fastest cure clinically and bacteriologically using least antibiotic. Ginecol Obstet Mex, 2002 Feb, 70, 90 - 4 {Frequency and etiology of seminal infections in the study of infertile couples}; Huerta M et al.; Male genital infections are a relevant cause in the etiology of infertility, due to abnormalities in sperm quality, affecting spermatozoal count and motility . OBJECTIVE: Identify the most common bacteria isolated from seminal cultures and their impact on seminal quality . MATERIAL AND METHODS: A retrospective, longitudinal and observational study was performed by reviewing 295 files of infertile males seen in our clinic of Reproductive Biology at the Hospital Juarez de Mexico, in whom seminogram and seminal cultures were practiced for detection of seminal infection and quality assessment . RESULTS: 47% of cases presented infection by one or two bacteria, Staphylococcus epidermidis, Streptococcus (alpha and beta hemolitic) and Escherichia coli prevailed . The main alterations in quality were motility, pH, morphology and viscosity in association with S . epidermidis and E . coli . CONCLUSIONS: Nearly half of our group of study disclosed seminal infections and it resembled the percentages reported in the literature; most of them were asymptomatic . In disparity with other reports the most common bacterial agent found in association with changes in seminal quality was a skin saprophyte. Compend Contin Educ Dent Suppl, 1997, 18(21), S17 - 21;quiz S46 Antibacterial activity of baking soda; Drake D; The antibacterial activity of baking soda (sodium bicarbonate) was assessed using three different experimental approaches . Standard minimum inhibitory concentration analyses revealed substantial inhibitory activity against Streptococcus mutans that was not due to ionic strength or high osmolarity . Short-term exposure assays showed significant killing of bacterial suspensions when baking soda was combined with the detergent sodium dodecylsulfate . Multiple, brief exposures of sucrose-colonized S mutans to baking soda and sodium dodecylsulfate caused statistically significant decreases in numbers of viable cells . Use of oral health care products with high concentrations of baking soda could conceivably result in decreased levels of cariogenic S mutans in saliva and plaque. J Endod, 2002 Mar, 28(3), 202 - 5 T lymphocyte subpopulations and interleukin-2, interferon-gamma, and interleukin-4 in rat pulpitis experimentally induced by specific bacteria; Kim SA et al.; The objective of this study was to investigate the expression of surface markers on T lymphocytes and the Th1/Th2 immune response in pulpal inflammation associated with specific bacteria . Pulpal inflammation was experimentally induced in rat mandibular incisors by drilling, without coolant, to open pulp chambers . Streptococcus mutans (S . mutans group), Porphyromonas endodontalis (P . endodontalis group), and a sterile cotton pellet only (control group) were inoculated in the canal . The expression of CD25 and CD54 on CD4+, and CD8+ lymphocytes in pulp tissues was determined by using a flow cytometer . The levels of interleukin (IL)-2, interferon (IFN)-gamma, and IL-4 were measured by ELISA . Flow-cytometric analysis showed that the mean ratio of CD4+:CD8+ was 0.96 in the control group, 0.99 in the S . mutans group, and 0.52 in the P . endodontalis group . An increase in CD25 and CD54 expression on CD4+ T lymphocytes was related to the bacterial infection (p < 0.05) and accompanied an increase in IL-2 concentration . The higher concentration of IFN-gamma than IL-4 in the P . endodontalis group suggested a Th1 reaction in the early stage of pulpal inflammation induced by P . endodontalis. J Biol Chem, 2002 Jul 26, 277(30), 26846 - 51 Epub 2002 May 16. Chimerism reveals a role for the streptokinase Beta -domain in nonproteolytic active site formation, substrate, and inhibitor interactions; Gladysheva IP et al.; Streptokinase (SK) and staphylokinase form cofactor-enzyme complexes that promote the degradation of fibrin thrombi by activating human plasminogen . The unique abilities of streptokinase to nonproteolytically activate plasminogen or to alter the interactions of plasmin with substrates and inhibitors may be the result of high affinity binding mediated by the streptokinase beta-domain . To examine this hypothesis, a chimeric streptokinase, SKbetaswap, was created by swapping the SK beta-domain with the homologous beta-domain of Streptococcus uberis Pg activator (SUPA or PauA, SK uberis), a streptokinase that cannot activate human plasminogen . SKbetaswap formed a tight complex with microplasminogen with an affinity comparable with streptokinase . The SKbetaswap-plasmin complex also activated human plasminogen with catalytic efficiencies (k(cat)/K(m) = 16.8 versus 15.2 microm(-1) min(-1)) comparable with streptokinase . However, SKbetaswap was incapable of nonproteolytic active site generation and activated plasminogen by a staphylokinase mechanism . When compared with streptokinase complexes, SKbetaswap-plasmin and SKbetaswap-microplasmin complexes had altered affinities for low molecular weight substrates . The SKbetaswap-plasmin complex also was less resistant than the streptokinase-plasmin complex to inhibition by alpha(2)-antiplasmin and was readily inhibited by soybean trypsin inhibitor . Thus, in addition to mediating high affinity binding to plasmin(ogen), the streptokinase beta-domain is required for nonproteolytic active site generation and specifically modulates the interactions of the complex with substrates and inhibitors. Am J Obstet Gynecol, 2002 May, 186(5), 869 - 71 The effect of temperature on bactericidal properties of 10% povidone-iodine solution; Leung MP et al.; OBJECTIVE: Ten percent povidone-iodine (PVI) is commonly used as a bactericidal solution before amniocentesis is performed . Warming PVI may increase patient comfort; however, the effect of warming on its bactericidal properties is not known . The objective of this study was to determine the effect of warming 10% PVI on its bactericidal properties . STUDY DESIGN: Room temperature of PVI was 25 degrees C, and temperature in an ultrasonic gel warmer was 32 degrees C . In vitro experiments were conducted in 25 degrees C and 32 degrees C water baths . Nine milliliters of PVI at each temperature was added to 1 mL of bacteria (10(7) organisms/mL Staphylococcus aureus, Enterococcus species, Escherichia coli, group B Streptococcus) . After 0.25, 0.5, 1, 2, 4, and 8 minutes, 1-mL samples were removed and added to 4 mL of 0.5% sodium thiosulfate (to neutralize the iodine and interrupt bactericidal action) . The number of viable organisms was determined by plating 0.1-mL samples on trypticase soy agar plates . Plates were incubated at 37 degrees C for 24 hours and colony-forming units (CFUs) were counted . For in vivo experiments in 40 volunteers, a 9-cm2 area of the dorsum of each hand was wiped with a sterile cotton swab to obtain a sample of bacteria for culture . The area was then wiped for 15 seconds with PVI at 25 degrees C or 32 degrees C and recultured . The bactericidal properties of PVI at each temperature were compared . The Mann-Whitney U test was used as appropriate, and P <.05 was considered significant . RESULTS: In vitro, PVI was bactericidal against E coli, S aureus, Enterococcus species, and group B Streptococcus within 0.25 minutes at both 25 degrees C and 32 degrees C, with median bacterial growth of 0 CFU/plate for each species of bacteria studied (3 replicates at each temperature) . Median bacterial growth from skin was 4 CFU/plate (range, 0 to >100) . After hands were wiped with PVI at 25 degrees C and 32 degrees C, median bacterial growth was 0 CFU/plate (range, 0-8) and 0 CFU/plate (range, 0-15), respectively (not significant) . CONCLUSION: PVI is as effective at 32 degrees C as it is at 25 degrees C . Use of PVI at 32 degrees C should be considered to increase patient comfort in procedures performed without the use of anesthetics. J Mal Vasc, 2002 Apr, 27(2), 82 - 7 {Vascular complications of infective endocarditis: a retrospective analysis of 18 cases}; Zarzur J et al.; OBJECTIVES: Among 82 patients hospitalized for infective endocarditis between June 1995 and June 2001 at the cardiology B unit of the Rabat University Hospital Morocco, 18 (22%) had one or more vascular complications . We present here a retrospective analysis . PATIENTS AND METHODS: The cohort included 12 men and 6 women, mean age 22 years . Infective endocarditis had grafted on a pre-existing cardiopathy among 17 patients: rheumatic heart disease (n=14), mechanical prosthetic valve (n=2), congenital heart disease (n=1) . RESULTS: For 12 patients, vascular disease was the only complication, 1 had two complications and 4 three complications . This gave 26 lesions: 11 neurological complications, 10 arterial diseases involving the limbs including 5 mycotic aneurysms, 2 acute myocardial infarcts, 2 splenic infarcts, and 1 recurrent septic pulmonary embolism . Vascular disease was the inaugural manifestation in 9 patients and 54% of the complications occurred before the end of the second week of antibiotic treatment . Blood cultures were positive in 7 patients (40%) . Oral streptococcus was isolated in 5 cases, Gram-negative bacillus in 1 case and Staphylococcus aureus in 1 . Echography revealed valvular vegetations in the 16 cases of infective endocarditis on native valves: mitral (n=9), aortic (n=5), mitroaortic (n=1), tricuspid (n=1) . Short term outcome was marked by 4 deaths including 3 directly related to the vascular complication . DISCUSSION: We emphasize the variable and diverse features of vascular complications of infective endocarditis . Prevention and early diagnosis are essential to institute optimal management of infective endocarditis. Curr Opin Infect Dis, 2002 Jun, 15(3), 253 - 7 Current concepts in the pathogenesis of meningitis caused by Streptococcus pneumoniae; Meli DN et al.; In spite of improved antimicrobial therapy, bacterial meningitis still results in brain damage leading to significant long-term neurological sequelae in a substantial number of survivors, as confirmed by several recent studies . Meningitis caused by Streptococcus pneumoniae is associated with a particularly severe outcome . Experimental studies over the past few years have increased our understanding of the molecular mechanisms underlying the events that ultimately lead to brain damage during meningitis . Necrotic damage to the cerebral cortex is at least partly mediated by ischemia and oxygen radicals and therefore offers a promising target for adjunctive therapeutic intervention . Neuronal apoptosis in the hippocampus may represent the major pathological process responsible for cognitive impairment and learning disabilities in survivors . However, the mechanisms involved in causing this damage remain largely unknown . Anti-inflammatory treatment with corticosteroids aggravates hippocampal damage, thus underlining the potential shortcomings of current adjuvant strategies . In contrast, the combined inhibition of matrix metalloproteinase and tumour necrosis factor-alpha converting enzyme protected both the cortex and hippocampus in experimental meningitis, and may represent a promising new approach to adjunctive therapy . It is the hope that a more refined molecular understanding of the pathogenesis of brain damage during bacterial meningitis will lead to new adjunctive therapies. Curr Opin Infect Dis, 2002 Jun, 15(3), 235 - 9 The role of pneumolysin in the pathogenesis of Streptococcus pneumoniae infection; Cockeran R et al.; In addition to being cytotoxic for eukaryotic cells, recent research has clearly indicated that pneumolysin at sub-cytolytic concentrations potentiates the proinflammatory activities of neutrophils and macrophages . Together these cytotoxic and proinflammatory activities of the toxin are likely to contribute to the virulence of the pneumococcus, particularly in facilitating adherence, invasion and dissemination of this important microbial pathogen . Pneumolysin-based vaccine strategies, although in the early stages of development and evaluation, show promise in reducing the severity of pneumococcal disease. Arch Oral Biol, 2002 May, 47(5), 347 - 59 Simultaneous measurement of the viability, aggregation, and live and dead adherence of Streptococcus crista, Streptococcus mutans and Actinobacillus actinomycetemcomitans in human saliva in relation to indices of caries, dental plaque and periodontal disease; Rudney JD et al.; Salivary proteins have multiple functions and many share similar functions, which may be why it has been difficult to relate variations in their concentrations to oral health and ecology . An alternative is to focus on variations in the major functions of saliva . An hydroxyapatite-coated microplate model has been developed that simultaneously measures saliva-promoted bacterial viability, bacterial aggregation, and live and dead bacterial adherence, while simulating oral temperature and shearing forces from swallowing . That model was applied to resting whole and stimulated parotid saliva from 149 individuals, using representative strains of Streptococcus crista, S . mutans, and Actinobacillus actinomycetemcomitans . Two major factors were defined by multivariate analysis (this was successful only for whole-saliva) . One factor was correlated with aggregation, live adherence and dead adherence for all three strains; the other was correlated with total viability of all three strains . Participants were grouped <25th percentile and >75th percentile for each factor . Those groups were compared for clinical indices of oral health . Caries scores were significantly lower in those with high scores for aggregation-adherence, regardless of whether total viability scores were low or high . Live bacteria always predominated on surfaces when live and dead adherence scores were expressed as ratios . However, participants with high scores for aggregation-adherence showed significantly more dead adherent bacteria than those with low scores (these ratios were uncorrelated with total viability) . This finding may indicate that extreme differences in the ability to kill bacteria on surfaces can influence caries risk. Arch Oral Biol, 2002 May, 47(5), 337 - 45 Partial characterization of a human submandibular/sublingual salivary adhesion-promoting protein; Akintoye SO et al.; Human submandibular/sublingual saliva contains a protein that promotes adhesion of Streptococcus mutans JBP serotype-c to spheroidal hydroxyapatite in vitro . A high molecular-weight (250,000-300,000 Da) adhesion-promoting protein (APP) was purified by Trisacryl 2000 M gel-filtration chromatography and gel electroelution before it was partially characterized . Lectin blotting identified that the terminal carbohydrates include N-acetyl glucosamine-beta 1-4-N-acetylglucosamine, galactose and galactose-beta 1-3-N-acetyl galactosamine . Antibodies to APP demonstrated no difference in the immunoreactive pattern of APP from saliva of caries-active or caries-resistant individuals belonging to four different ethnic groups: Asian, African-American, Hispanic or Caucasian . No immunological similarities to salivary mucins or parotid agglutinins were detected by Western blotting using immuno-cross-reactivity as a criterion . APP appears to be a unique protein found in submandibular/sublingual saliva . Understanding such a protein could help prevent S . mutans attachment to the enamel surface. Eur J Pediatr, 2002 Apr, 161(4), 188 - 95 Pneumococcal disease in western Europe: burden of disease, antibiotic resistance and management; Cartwright K; Streptococcus pneumoniae- the pneumococcus- affects children and adults worldwide . Invasive pneumococcal disease, including pneumonia, meningitis and bacteraemia, has been linked annually to the deaths of millions of children . The pneumococcus is also a significant contributor to mucosal infections such as acute otitis media and sinusitis . Though pneumococcal infections can occur at any age, persons at greatest risk include children younger than 2 years of age and adults aged 65 years or more . Rates of pneumococcal disease and the prevalence of pneumococcal serotypes vary by geographic location and patient age . Accurate ascertainment and sound epidemiological data are essential for the rational development of effective programmes for prevention and treatment . Pneumococcal resistance to penicillin and other antibiotics has emerged rapidly in recent years, highlighting the importance of vaccine development . Newer pneumococcal vaccines, such as those conjugated to protein carriers, can now overcome the limitations of older polysaccharide vaccines . Such conjugated vaccines induce excellent immune responses even in infants and young children and they may also reduce asymptomatic nasopharyngeal carriage of pneumococci . Pneumococcal 7-valent conjugated vaccine PNCRM7 contains common prevalent serotypes coupled to a nontoxic diphtheria variant (CRM197) . This vaccine has demonstrated high efficacy against invasive pneumococcal disease in clinical trials in infants and young children and is currently licensed for use in the United States and selected countries in Europe and Latin America . CONCLUSION: across Europe, pneumococcal infection is responsible for considerable morbidity and mortality, particularly in the very young and the elderly, groups whose members respond poorly to non-conjugated vaccines . The advent of new conjugated pneumococcal vaccines now offers an exciting opportunity in developed countries to reduce both the current burden of disease and the threat of rising antibiotic resistance . Rolling out the use of such vaccines across Europe must be accompanied by detailed ongoing surveillance in order to detect any changes that might occur in the pattern of pneumococcal serotypes. Pharmacotherapy, 2002 May, 22(5), 593 - 6 Serum bactericidal activity of extended-release clarithromycin against macrolide-resistant strains of Streptococcus pneumoniae; Stein GE et al.; STUDY OBJECTIVE: To investigate the serum bactericidal activity (SBA) over time of extended-release clarithromycin against moderately resistant strains of Streptococcus pneumoniae . DESIGN: Prospective, single-dose pharmacodynamic study . SETTING: University-affiliated research center . SUBJECTS: Eleven healthy male volunteers . INTERVENTION: All volunteers received a single dose of extended-release clarithromycin as two 500-mg tablets, and blood samples were obtained at 0, 2, 6, 12, and 24 hours after administration of the dose . MEASUREMENTS AND MAIN RESULTS: For each blood sample, a serum bactericidal titer (SBT) was determined against S . pneumoniae strains with minimum inhibitory concentrations (MICs) of 0.5, 1.0, 2.0, 4.0, and 8.0 microg/ml to clarithromycin . The median SBT was determined for each time period . The extended-release formulation of clarithromycin exhibited SBA for 24 hours against pneumococcal strains with MICs of 0.5, 1.0, and 2.0 microg/ml . No SBA was observed against isolates with MICs of 4.0 or 8.0 microg/ml . CONCLUSION: The extended-release formulation of clarithromycin, taken once/day, will provide SBA for 24 hours against strains of S . pneumoniae with MICs of 2.0 microg/ml or less. J Fr Ophtalmol, 2002 Apr, 25(4), 375 - 8 {Necrotizing fasciitis of the eyelids and orbit: a life-threatening ophthalmological emergency}; Costet-Fighiera C et al.; Introduction: Necrotizing fasciitis is an extremely serious exceptional infectious process affecting subcutaneous soft tissues with skin gangrene and vascular thromboses . Starting from a case repat of necrotizing fasciitis of the eyelids and orbit, which occurred in a child of 4, we analyse the early diagnostic elements and the urgency of treatment of a pathology which can rapidly be life-threatening . Observation: A child, aged 4 presented a necrotizing fasciitis of the eyelid and orbit with serious toxic shock, after minor skin abrasion . RESULT: Resuscitation and parenteral antibiotic therapy were not sufficient to stop the necrotizing process, which required surgical debridement of gangrenous tissues . DISCUSSION: Necrotizing fasciitis is a rare affection with fatal local and general prognosis . Location on the orbit and eyelids is extremely rare, with only a score of cases recorded in the literature, principally in adults . Our observation shows the possibility of occurrence in a young child and found the typical features of the pathology: minor initial trauma, beta hemolytic streptococcus, extremely fast progression requiring resuscitation, extensive antibiotic therapy and surgical excision of the gangrenous tissues . Eyesight remained intact, but cases of blindness have been described in the literature . Secondary reconstructive surgery on the eyelids may be necessary . CONCLUSION: Urgent diagnosis of this exceptional pathology that may affect the young child and prompt antibiotic therapy and surgical debridement are the only guarantees of survival of infected patients. Infect Immun, 2002 Jun, 70(6), 3227 - 33 Dissemination of the phage-associated novel superantigen gene speL in recent invasive and noninvasive Streptococcus pyogenes M3/T3 isolates in Japan; Ikebe T et al.; In Japan, more than 10% of streptococcal toxic shock-like syndrome (TSLS) cases have been caused by Streptococcus pyogenes M3/T3 isolates since the first reported TSLS case in 1992 . Most M3/T3 isolates from TSLS or severe invasive infection cases during 1992 to 2001 and those from noninvasive cases during this period are indistinguishable in pulsed-field gel electropherograms . The longest fragments of these recent isolates were 300 kb in size, whereas those of isolates recovered during or before 1973 were 260 kb in size . These 260- and 300-kb fragments hybridized to each other, suggesting the acquisition of an about 40-kb fragment by the recent isolates . The whole part of the acquired fragment was cloned from the first Japanese TSLS isolate, NIH1, and its nucleotide sequence was determined . The 41,796-bp fragment is temperate phage phiNIH1.1, containing a new superantigen gene speL near its right attachment site . The C-terminal part of the deduced amino acid sequence of speL has 48 and 46% similarity with well-characterized erythrogenic toxin SpeC and the most potent superantigen, SmeZ-2, respectively . None of 10 T3 isolates recovered during or before 1973 has speL, whereas all of 18 M3/T3 isolates recovered during or after 1992 and, surprisingly, Streptococcus equi subsp . equi ATCC 9527 do have this gene . Though plaques could not be obtained from phiNIH1.1, its DNA became detectable from the phage particle fraction upon mitomycin C induction, showing that this phage is not defective . A horizontal transfer of the phage carrying speL may explain the observed change in M3/T3 S . pyogenes isolates in Japan. Infect Immun, 2002 Jun, 70(6), 2886 - 90 Upper and lower respiratory tract infection by Streptococcus pneumoniae is affected by pneumolysin deficiency and differences in capsule type; Kadioglu A et al.; Pneumococci frequently colonize the upper respiratory tract, and these pneumococci are believed to act as a reservoir for infection of the lower respiratory tract and bacteremia . We investigated how the pneumococcal toxin pneumolysin affects the capacity of pneumococci to infect the upper and lower respiratory tract of the mouse . Wild-type Streptococcus pneumoniae serotype 2 and 3 strains, a serotype 2 pneumolysin-deficient mutant, and a serotype 2 mutant with the pneumolysin gene reinserted were used to study differences in colonization and disease . In addition, we also examined a pneumococcal chimeric mutant (capsule type switched from serotype 2 to serotype 3) to gain further insight into the role that capsule plays in nasopharyngeal infection . Absence of pneumolysin was found to be associated with significantly lower numbers of pneumococci in the nasopharynx, trachea, and lungs . Differences in pneumococcal capsule type were found to have significant effects on pneumococcal infection of the nasopharynx, trachea, and lungs . However, it was the combination of capsule type and genetic background that was important, and the influence of this combination varied with the site of infection . For example, in the nasopharynx the wild-type serotype 3 strain and the capsule-switched mutant behaved similarly, whereas in the lungs the mutant that was switched to serotype 3 survived less well than the wild-type serotype 3 strain . The combination of capsule type and genetic background also determined virulence . Thus, the wild-type serotype 3 strain was virulent, whereas the capsule-switched mutant was avirulent. Infect Immun, 2002 Jun, 70(6), 2862 - 8 Regulatory role of interleukin-10 in experimental group B streptococcal arthritis; Puliti M et al.; Intravenous inoculation of CD-1 mice with 10(7) CFU of type IV group B Streptococcus (GBS) results in a high incidence of diffuse septic arthritis, associated with high levels of systemic and local production of interleukin-1beta (IL-1beta) and IL-6 . In this study, the role of the anti-inflammatory cytokine IL-10 in the evolution of GBS systemic infection and arthritis was evaluated . IL-10 production was evident in sera and joints of GBS-infected mice . Neutralization of endogenous IL-10 by administration of anti-IL-10 antibodies (1 mg/mouse) at the time of infection resulted in worsening of articular lesions and 60% mortality associated with early sustained production of IL-6, IL-1beta, and tumor necrosis factor alpha (TNF-alpha) . The effect of IL-10 supplementation was assessed by administering IL-10 (100, 200, or 400 ng/mouse) once a day for 5 days, starting 1 h after infection . Treatment with IL-10 had a beneficial effect on GBS arthritis, and there was a clear-cut dose dependence . The decrease in pathology was associated with a significant reduction in IL-6, IL-1beta, and TNF-alpha production . Histological findings showed limited periarticular inflammation and a few-cell influx in the articular cavity of IL-10-treated mice, confirming clinical observations . In conclusion, this study provides further information concerning the role of IL-10 in regulating the immune response and inflammation and calls attention to the potential therapeutic use of IL-10 in GBS arthritis. Infect Immun, 2002 Jun, 70(6), 2805 - 11 The in vitro interaction of Streptococcus pyogenes with human pharyngeal cells induces a phage-encoded extracellular DNase; Broudy TB et al.; The role lysogenic bacteriophage play in the pathogenesis of the host bacterium is poorly understood . In a previous study, we found that streptococcal coculture with human pharyngeal cells resulted in the induction of lysogenic bacteriophage as well as the phage-associated streptococcal pyrogenic exotoxin C (SpeC) . In this study, we have determined that in addition to SpeC induction, a number of other streptococcal proteins are also released by the bacteria during coculture with pharyngeal cells . Among these, we identified and characterized a novel 27-kDa secreted protein . Sequence analysis of this novel protein demonstrated it to be encoded by the same lysogenic bacteriophage which harbors speC . Protein sequence analysis revealed varied homologies with several streptococcal DNases . Further biochemical characterization of the recombinantly expressed protein verified it to be a divalent cation-dependent streptococcal phage-encoded DNase (Spd1) . Although functionally distinct, SpeC and Spd1 are associated by a number of parameters, including genetic proximity and transcriptional regulation . Finally, we speculate on the induction of phage-encoded DNase (Spd1) enhancing the fitness of both bacteria and phage. Mol Microbiol, 2002 May, 44(4), 1081 - 94 An accessory sec locus of Streptococcus gordonii is required for export of the surface protein GspB and for normal levels of binding to human platelets; Bensing BA et al.; The translocation of proteins across the bacterial cell membrane is carried out by highly conserved components of the Sec system . Most bacterial species have a single copy of the genes encoding SecA and SecY, which are essential for viability . However, Streptococcus gordonii strain M99 encodes SecA and SecY homologues that are not required for viability or for the translocation of most exported proteins . The genes (secA2 and secY2) reside in a region of the chromosome required for the export of GspB, a 286 kDa cell wall-anchored protein . Loss of GspB surface expression is associated with a significant reduction in the binding of M99 to human platelets, suggesting that it may be an adhesin . Genetic analyses indicate that M99 has a second, canonical SecA homologue that is essential for viability . At least two other Gram-positive species, Streptococcus pneumoniae and Staphylococcus aureus, encode two sets of SecA and SecY homologues . One set is more similar to SecA and SecY of Escherichia coli, whereas the other set is more similar to SecA2 and SecY2 of strain M99 . The conserved organization of genes in the secY2-secA2 loci suggests that, in each of these Gram-positive species, SecA2 and SecY2 may constitute a specialized system for the transport of a very large serine-rich repeat protein. Mol Microbiol, 2002 May, 44(4), 917 - 34 Uptake and intracellular transportation of a bacterial surface protein in lymphoid cells; Frick IM et al.; Some strains of the human pathogen Streptococcus pyogenes express a surface protein called protein H, which is released from the streptococcal surface by a cysteine proteinase produced by the bacteria . Here, we find that soluble protein H binds to the surface of lymphocytes and granulocytes, and that the molecule is taken up by lymphocytes and transported to the perinuclear region . The translocation over the cell membrane is rapid, and the uptake and intracellular transportation is not dependent on actin polymerization . Protein H could be immunoprecipitated from cell extracts and nuclear preparations of lymphocytes, and analysis of molecular interactions between protein H and proteins of different cellular compartments demonstrated a binding to nucleophosmin/ B23, a protein known to shuttle between the cytoplasm and the nucleus, and to the nuclear proteins SET and hnRNP A2/B1 . Nucleophosmin/B23 was co-immunoprecipitated with protein H from cell and nuclear extracts, and binding experiments, including kinetic analyses, suggest that protein H dissociating from nucleophosmin/B23 complexes in the perinuclear region or in the nucleus binds to proteins SET and hnRNP A2/B1 . Finally, the uptake and intracellular transportation of protein H was found to result in a cytostatic effect on B and T lymphocytes. Biochemistry, 2002 May 21, 41(20), 6398 - 407 Mutagenesis and mechanism-based inhibition of Streptococcus pyogenes Glu-tRNAGln amidotransferase implicate a serine-based glutaminase site; Harpel MR et al.; The absence of Gln-tRNA synthetase in certain bacteria necessitates an alternate pathway for the production of Gln-tRNA(Gln): misacylated Glu-tRNA(Gln) is transamidated by a Gln-dependent amidotransferase (Glu-AdT) via catalysis of Gln hydrolysis, ATP hydrolysis, activation of Glu-tRNA(Gln), and aminolysis of activated tRNA by Gln-derived NH(3) . As observed for other Gln-coupled amidotransferases, substrate binding, Gln hydrolysis, and transamidation by Glu-AdT are tightly coordinated {Horiuchi, K . Y., Harpel, M . R., Shen, L., Luo, Y., Rogers, K . C., and Copeland, R . A . (2001) Biochemistry 40, 6450-6457} . However, Glu-AdT does not employ an active-site Cys nucleophile for Gln hydrolysis, as is common in all other glutaminases: some Glu-AdT lack Cys, but all contain a conserved Ser (Ser176 in the A subunit of Streptococcus pyogenes Glu-AdT) within a sequence signature motif of Ser-based amidases . Our current results with S . pyogenes Glu-AdT support this characterization of Glu-AdT as a Ser-based glutaminase . Slow-onset (approximately 50 M(-1) s(-1)), tight-binding (t(1/2) > 2.5 h for complex dissociation), Gln-competitive inhibition of the Glu-tRNA(Gln)/ATP-independent glutaminase activity of Glu-AdT by gamma-Glu boronic acid is consistent with engagement of a Ser nucleophile in the glutaminase active site . Conversion to rapidly reversible, yet still potent (K(i) = 73 nM) and Gln-competitive, inhibition under full transamidation conditions mirrors the coupling between Gln hydrolysis and aminolysis reactions during productive transamidation . Site-directed replacement of Ser176 by Ala abolishes glutaminase and Gln-dependent transamidase activities of Glu-AdT (>300-fold), but retains a wild-type level of NH(3)-dependent transamidation activity . These results demonstrate the essentiality of Ser176 for Gln hydrolysis, provide additional support for coordinated coupling of Gln hydrolysis and transamidase transition states during catalysis, and validate glutaminase-directed inhibition of Glu-AdT as a route for antimicrobial chemotherapy. Vaccine, 2002 May 22, 20(17-18), 2278 - 86 Immunisation of dairy cattle with recombinant Streptococcus uberis GapC or a chimeric CAMP antigen confers protection against heterologous bacterial challenge; Fontaine MC et al.; The gapC genes, encoding the cell surface-associated GapC proteins of S . uberis and S . agalactiae, have been cloned and sequenced . To identify potential vaccine candidates against S . uberis-induced bovine mastitis, lactating dairy cows were vaccinated with either (6 x His)GapC of S . uberis or S . dysgalactiae, or with a chimeric CAMP-factor antigen, CAMP-3 . For 7 days following heterologous challenge with S . uberis, milk somatic cell counts were determined to assess differences in the severity of mastitis between vaccinates and an unvaccinated control group . Vaccination with S . uberis (6 x His)GapC or CAMP-3 resulted in a significant reduction in inflammation on several days post-challenge, most significantly for the former antigen . Inflammation was not reduced in S . dysgalactiae (6 x His)GapC vaccinates, suggesting that it does not confer cross-species protection. Vaccine, 2002 May 22, 20(17-18), 2174 - 80 Streptococcus pneumoniae polysaccharides conjugated to the outer membrane protein A from Klebsiella pneumoniae elicit protective antibodies; Libon C et al.; Polysaccharides (PSs) derived from Streptococcus pneumoniae include more than 90 serotypes and differ greatly in their immunogenicity . In addition, immunization with PSs does not induce high affinity antibody production and no memory B-cells are generated . Coupling PSs to carrier proteins has been reported to induce B-cell maturation and to install a B-cell memory . As an alternative carrier protein, the outer membrane protein A (OmpA) derived from Klebsiella pneumoniae has been coupled to various PSs . We evaluated the immunogenicity of two PS conjugates, using PS derived from S . pneumoniae types 14 and 19 . In this report, we show that anti-PS IgG responses are generated after the conjugation of PSs to P40 . In addition, the humoral response generated is able to protect mice from a bacterial challenge . Our results indicate that P40 could be included in the development of new PS conjugate vaccines. FEMS Microbiol Lett, 2002 Mar 19, 209(1), 75 - 9 Pathways for lactose/galactose catabolism by Streptococcus salivarius; Chen YY et al.; Galactokinase and beta-galactosidase-deficient strains of Streptococcus salivarius were constructed to define the pathways for lactose and galactose catabolism . It was found that S . salivarius does not possess a lactose-specific phosphoenolpyruvate phosphotransferase system (PTS), that intracellular lactose was hydrolyzed by beta-galactosidase, and that galactose is catabolized exclusively through the Leloir pathway . The lack of a high-affinity PTS for lactose may reflect the higher availability of the substrates to soft tissue organisms, such as S . salivarius, compared to dental plaque bacteria. Pediatr Infect Dis J, 2002 Mar, 21(3), 186 - 92 Antibody response to pneumococcal capsular polysaccharides in children with acute otitis media; Soininen A et al.; BACKGROUND: To describe the antibody response to pneumococcal capsular polysaccharides in children <2 years of age with pneumococcal acute otitis media (AOM) caused by serotypes 6A, 6B, 11A, 14, 19F or 23F . These serotypes were commonly found in both nasopharyngeal carriage and AOM in children of the study population in Finland . METHODS: Serum antibody concentrations to pneumococcal capsular polysaccharides of types 6B, 11A, 14, 19F and 23F were measured by enzyme immunoassay in acute and convalescent sera from children with AOM . RESULTS: Responses (at least 2-fold increase of antibody concentration) were relatively infrequent and varied with both the age of the child and the serotype of the Streptococcus pneumoniae isolated from the middle ear fluid . Children older than 12 months were more likely to have antibody responses than were younger children . Responses were seen only infrequently to types 6A, 6B or 19F (1 of 14, 1 of 9 and 2 of 25, respectively), more often to types 11A and 14 (2 of 8 and 3 of 8) and relatively frequently to type 23F (8 of 18) . However, the convalescent antibody concentrations to type 23F were low and usually declined after the infection, whereas responders to 14 AOM had antibodies that persisted at a high concentration through the follow-up . CONCLUSIONS: The results emphasize the differences between Streptococcus pneumoniae serotypes in their immunogenicity and quantitative and qualitative differences of antibodies produced after infection. J Antimicrob Chemother, 2002 May, 49(5), 821 - 6 A prospective, multicentre study of moxifloxacin concentrations in the sinus mucosa tissue of patients undergoing elective surgery of the sinus; Gehanno P et al.; A pharmacokinetic study was carried out to determine moxifloxacin concentrations in sinus tissue, after oral moxifloxacin 400 mg once daily for 5 days to patients with chronic sinusitis, undergoing elective sinus surgery . Patients were randomly allocated to one of seven treatment groups, in which tissues were sampled 2, 3, 4, 6, 12, 24 or 36 h post-dose . A control group with non-infected nasal polyps was also included . Forty-eight patients (13 female, 35 male, mean age 47.1 years) were allocated to one of each active treatment group (n = 42) or to the control group (n = 6) . Tissue and plasma samples were taken simultaneously and stored frozen until assayed by HPLC . Thirty-nine patients were fully valid for pharmacokinetic analysis . The geometric mean moxifloxacin plasma concentration increased from 2.32 mg/L at 2 h to a maximum of 3.37 mg/L at 4 h post-dose, decreasing to 0.37 mg/L at 36 h post-dose . The moxifloxacin concentration in sinus mucosa was consistently greater than that in plasma being 4.56-5.73 mg/kg from 2 to 6 h and 2.81-1.25 mg/kg from 12 to 36 h post-dose . The elimination rates in plasma and sinus tissues were similar . The tissue/plasma ratio was c . 200% between 2 and 6 h, and up to 328.9% at 36 h . Results were similar whatever the site of tissue sampling (maxillary sinus, anterior ethmoid sinus or nasal polyps) . Tissue levels exceeded the MIC(90) of all pathogens commonly causing acute sinusitis (e.g . 5-30 x MIC for Streptococcus pneumoniae: 0.25 mg/L) . These results sup-port the use of moxifloxacin 400 mg once daily as a regimen for the treatment of sinus infections. J Antimicrob Chemother, 2002 May, 49(5), 807 - 12 Pharmacodynamic activity of fluoroquinolones against ciprofloxacin-resistant Streptococcus pneumoniae; Zhanel GG et al.; The susceptibility and pharmacodynamic activity of ciprofloxacin and new fluoroquinolones were studied against low-level (MIC 4 mg/L) and high-level (MIC 16 mg/L) ciprofloxacin-resistant Streptococcus pneumoniae . An in vitro pharmacodynamic model simulating free fluoroquinolone (protein unbound) serum concentrations, using Cp(max) and AUC(0-24) achieved (in healthy volunteers) after standard oral doses that are used for community-acquired respiratory infections, was used to compare bacterial killing by five fluoroquinolones against six ciprofloxacin-resistant S . pneumoniae isolates (four different resistance mutant phenotypes: ParC, efflux, ParC with efflux, and ParC and GyrA) obtained from an ongoing Canadian respiratory organism surveillance study . The potency (MIC only) of fluoroquinolones was gemifloxacin > moxifloxacin > gatifloxacin > levofloxacin > ciprofloxacin . Ciprofloxacin (free AUC(0-24)/MIC 0.9-3.5) produced no reduction of growth at 6, 24 or 48 h compared with the initial inoculum in all six strains . Levofloxacin (free AUC(0-24)/MIC 18-35) was bactericidal (> or = 3 log(10) killing) at 6, 24 and 48 h for the ParC as well as the efflux mutants, but only bactericidal at 24 h for the ParC with efflux strain . Levofloxacin (free AUC(0-24)/MIC 4.4) demonstrated no reduction of growth relative to the initial inoculum against the ParC and GyrA mutants . Gatifloxacin and moxifloxacin (free AUC(0-24)/MIC 48 and 60, respectively) were bactericidal at 6, 24 and 48 h against the ParC, efflux, and ParC with efflux mutants, but demonstrated little to no growth reduction (free AUC(0-24)/MIC 6 and 7.5, respectively) in ParC and GyrA mutants . Gemifloxacin (free AUC(0-24)/MIC 67-133) was bactericidal (> or = 3 log(10) killing) at 6, 24 and 48 h in all low-level ciprofloxacin-resistant S . pneumoniae mutants . Against two of the ParC and GyrA mutants, gemifloxacin (free AUC(0-24)/MIC 32) was bactericidal at 6, 24 and 48 h but against one ParC and GyrA mutant (free AUC(0-24)/MIC 16) gemifloxacin demonstrated reduced activity with initial killing at 24 h but with subsequent regrowth . These data indicate that ciprofloxacin produces no inhibition of growth of low- or high-level ciprofloxacin-resistant S . pneumoniae, whereas gatifloxacin, levofloxacin and moxifloxacin (moxifloxacin>gatifloxacin>levofloxacin) were bactericidal for low-level resistant strains but produced little or no inhibition of high-level resistant strains . Gemifloxacin at simulated free AUC(0-24)/MIC > or = 32, was bactericidal against low- and high-level resistant strains . When simulated free AUC(0-24)/ MIC was <16, gemifloxacin allowed regrowth of high-level ciprofloxacin-resistant strains. J Bacteriol, 2002 Jun, 184(11), 2931 - 9 An iron-binding protein, Dpr, from Streptococcus mutans prevents iron-dependent hydroxyl radical formation in vitro; Yamamoto Y et al.; The dpr gene is an antioxidant gene which was isolated from the Streptococcus mutans chromosome by its ability to complement an alkyl hydroperoxide reductase-deficient mutant of Escherichia coli, and it was proven to play an indispensable role in oxygen tolerance in S . mutans . Here, we purified the 20-kDa dpr gene product, Dpr, from a crude extract of S . mutans as an iron-binding protein and found that Dpr formed a spherical oligomer about 9 nm in diameter . Molecular weight determinations of Dpr in solution by analytical ultracentrifugation and light-scattering analyses gave values of 223,000 to 292,000, consistent with a subunit composition of 11.5 to 15 subunits per molecule . The purified Dpr contained iron and zinc atoms and had an ability to incorporate up to 480 iron and 11.2 zinc atoms per molecule . Unlike E . coli Dps and two other members of the Dps family, Dpr was unable to bind DNA . One hundred nanomolar Dpr prevented by more than 90% the formation of hydroxyl radical generated by 10 microM iron(II) salt in vitro . The data shown in this study indicate that Dpr may act as a ferritin-like iron-binding protein in S . mutans and may allow this catalase- and heme-peroxidase-deficient bacterium to grow under air by limiting the iron-catalyzed Fenton reaction. J Bacteriol, 2002 Jun, 184(11), 2878 - 88 Intramolecular regulation of the opposing (p)ppGpp catalytic activities of Rel(Seq), the Rel/Spo enzyme from Streptococcus equisimilis; Mechold U et al.; Catalytic and regulatory domains of the Rel/Spo homolog of Streptococcus equisimilis affecting (p)ppGpp synthesis and degradation activities have been defined, and opposing activities of the purified protein and its fragments have been compared . Two major domains of the 739-residue Rel(Seq) protein are defined by limited proteolytic digestion . In vitro assays of the purified N-terminal half-protein reveal synthesis of (p)ppGpp by an ATP-GTP 3'-pyrophosphotransferase as well as an ability to degrade (p)ppGpp by a Mn(2+)-dependent 3'-pyrophosphohydrolase . Removal of the C-terminal half-protein has reciprocal regulatory effects on the activities of the N-terminal half-protein . Compared to the full-length protein, deletion activates (p)ppGpp synthesis specific activity about 12-fold and simultaneously inhibits (p)ppGpp degradation specific activity about 150-fold to shift the balance of the two activities in favor of synthesis . Cellular (p)ppGpp accumulation behavior is consistent with these changes . The bifunctional N-terminal half-protein can be further dissected into overlapping monofunctional subdomains, since purified peptides display either degradation activity (residues 1 to 224) or synthetic activity (residues 79 to 385) in vitro . These assignments can also apply to RelA and SpoT . The ability of Rel(Seq) to mediate (p)ppGpp accumulation during amino acid starvation in S . equisimilis is absent when the protein is expressed ectopically in Escherichia coli . Fusing the N-terminal half of Rel(Seq) with the C-terminal domain of RelA creates a chimeric protein that restores the stringent response in E . coli by inhibiting unregulated degradation and restoring regulated synthetic activity . Reciprocal intramolecular regulation of the dual activities may be a general intrinsic feature of Rel/Spo homolog proteins. J Chemother, 2002 Feb, 14 Suppl 2, 13 - 21 Pharmacokinetic and pharmacodynamic predictors of antimicrobial efficacy: moxifloxacin and Streptococcus pneumoniae; Schentag JJ; Infections caused by Streptococcus pneumoniae place a considerable personal and economic burden on both patients and healthcare systems . As the resistance of S . pneumoniae to older antimicrobial agents such as penicillin, cephalosporins, and macrolides has increased, new antimicrobials with good activity against S . pneumoniae have been developed . The newer fluoroquinolones, including levofloxacin, gatifloxacin and moxifloxacin provide a safe and easy tool in the treatment of S . pneumoniae infections . However, there have been recent reports of levofloxacin-resistant strains of S . pneumoniae . Pharmacokinetics and pharmacodynamics can be used to determine which fluoroquinolone delivers the best coverage against S . pneumoniae, and also the 24-h AUC/MIC ratio (the AUIC) required to impede the emergence of bacterial resistance . Monte Carlo analysis suggests that moxifloxacin, with 4-8-fold greater activity and higher AUIC against S . pneumoniae than levofloxacin or gatifloxacin, provides the best coverage in terms of probability of cure and probability of minimizing emergence of resistance. Crit Rev Microbiol, 2002, 28(1), 27 - 41 Development and evaluation of pneumococcal conjugate vaccines: clinical trials and control tests; Lee LH et al.; Streptococcus pneumoniae is a major cause of pneumonia, meningitis, and otitis media and is responsible for disease in young children, the elderly, and immunocompromised individuals . Emerging high-level resistance to penicillin, multiple antibiotics, and tolerance to vancomycin emphasizes the importance of preventing pneumococcal infection by alternative methods such as immunization . The development of pneumococcal conjugate vaccines using the same carrier proteins as those used in Hemophilus influenzae type b vaccines has enhanced the immune response in infants and children compared with polysaccharide vaccines and has significantly improved the ability to prevent pneumococcal disease in this population worldwide . Here we review the clinical trials of multivalent pneumococcal conjugate vaccines under evaluation, identify potential carrier proteins considered for development of future pneumococcal conjugate vaccines, discuss issues regarding licensure of new candidate vaccines from a clinical trial and quality control perspective, and alternative vaccine strategies for the prevention of pneumococcal disease. Crit Rev Oral Biol Med, 2000, 11(2), 140 - 58 Passive immunization against dental caries and periodontal disease: development of recombinant and human monoclonal antibodies; Abiko Y; Indigenous micro-organisms in the oral cavity can cause two major diseases, dental caries and periodontal diseases . There is neither agreement nor consensus as to the actual mechanisms of pathogenesis of the specific virulence factors of these micro-organisms . The complexity of the bacterial community in dental plaque has made it difficult for the single bacterial agent of dental caries to be determined . However, there is considerable evidence that Streptococcus mutans is implicated as the primary causative organism of dental caries, and the cell-surface protein antigen (SA I/II) as well as glucosyltransferases (GTFs) produced by S . mutans appear to be major colonization factors . Various forms of periodontal diseases are closely associated with specific subgingival bacteria . Porphyromonas gingivalis has been implicated as an important etiological agent of adult periodontitis . Adherence of bacteria to host tissues is a prerequisite for colonization and one of the important steps in the disease process . Bacterial coaggregation factors and hemagglutinins likely play major roles in colonization in the subgingival area . Emerging evidence suggests that inhibition of these virulence factors may protect the host against caries and periodontal disease . Active and passive immunization approaches have been developed for immunotherapy of these diseases . Recent advances in mucosal immunology and the introduction of novel strategies for inducing mucosal immune responses now raise the possibility that effective and safe vaccines can be constructed . In this regard, some successful results have been reported in animal experimental models . Nevertheless, since the public at large might be skeptical about the seriousness of oral diseases, immunotherapy must be carried out with absolute safety . For this goal to be achieved, the development of safe antibodies for passive immunization is significant and important . In this review, salient advances in passive immunization against caries and periodontal diseases are summarized, and the biotechnological approaches for developing recombinant and human-type antibodies are introduced . Furthermore, our own attempts to construct single-chain variable fragments (ScFv) and human-type antibodies capable of neutralizing virulence factors are discussed. Microb Drug Resist, 2002 Spring, 8(1), 73 - 6 Streptococcus pneumoniae as an etiologic agent in infectious complications of pancreatic disease; Thege MK et al.; Systematic culturing of perioperative intra-abdominal samples allowed us to recognize the presence of Streptococcus pneumoniae in infectious complications of chronic pancreatitis in 9 male patients . In 8 of 10 of the intra- or peripancreatic samples, S . pneumoniae was the single isolate identified . All but one of the S . pneumoniae isolates were sensitive to penicillin . The patients had predisposing underlying conditions such as alcoholism and diabetes mellitus . All patients were cured due to adequate surgery and antibiotic treatment . Analysis of the case histories suggests that S . pneumoniae may have been a relevant organism causing the infectious complications of pancreatitis in these patients. Epidemiol Infect, 2002 Apr, 128(2), 139 - 47 Incidence of invasive pneumococcal disease in Scotland, 1988-99; Kyaw MH et al.; A review of the epidemiology of invasive pneumococcal disease in Scotland was carried out using data from laboratory-based systems during the period 1988-99 . This comprised 5456 (90.8%) isolates of Streptococcus pneumoniae from blood, 467 (7.8%) from cerebrospinal fluid (CSF) and 84 (1.4%) from other sterile sites . The mean annual incidence of invasive disease was 9.8/10(5) population (9.0/10(5) for bacteraemia and 0.8/10(5) for meningitis) . Invasive disease was highest in children < 2 years of age and in the elderly > or = 65 years (44.9/10(5) and 28.4/10(5) population in these age groups respectively) . The highest incidence of pneumococcal meningitis, 11.8/10(5) persons occurred in children < 2 years of age . Males had a higher incidence of pneumococcal bacteraemia and meningitis than females (male:female = 1.2:1 for bacteraemia (RR = 1.17, 95 % CI 1.11, 1.24) and 1.5:1 for meningitis (RR = 1.41, 95 % CI 1.18, 1.70)) . Pneumococcal disease was highest in winter periods and coincided with influenza activity . The proportion of penicillin and erythromycin non-susceptible isolates increased from 4.2% in 1992 to 12.6% in 1999 and from 5.6% in 1994 to 16.3% in 1999 respectively . Our data confirm the substantial and increasing disease burden from pneumococcal disease and rise in prevalence of antibiotic non-susceptibility among pneumococci in Scotland . Continued surveillance of groups at increased risk for pneumococcal disease and the antibiotic susceptibility and serotype distribution of isolates are important to develop appropriate policies for the prevention of pneumococcal disease in Scotland. Curr Microbiol, 2002 Jun, 44(6), 435 - 43 Effects of exogenous ammonia or free amino acids on proteolytic activity and protein breakdown products in Streptococcus bovis, Prevotella albensis, and Butyrivibrio fibrisolvens; Sales-Duval M et al.; We studied in details the ammonia or free amino acids (AA) effects on proteolytic activity of three ruminal bacteria: enzymatic activities and protein breakdown products were measured at the end of the exponential growth phase . In Streptococcus bovis the simultaneous uptake of ammonia and probably small peptides induced a decline in total proteolytic activity as a result of changes in endopeptidasic activities . With free AA, the tendency for the endopeptidasic activities to specialise was more evident and the total proteolytic activity decreased too . In Prevotella albensis, the inhibition of proteolysis with free AA was linked to the disappearance of free endopeptidases, to the specialization of cell-associated endopeptidases and to the decrease in exopeptidases . The decrease of proteolysis in P . albensis when ammonia was added was more difficult to interpret . With ammonia or AA Butyrivibro fibrisolvens developed a distinct behavior of those expressed by the other species: the increase of the total proteolytic activity could be explained by a better balance of the endopeptidases expressed . It then clearly appeared that the expression of the proteolytic activities are linked to the nature and/or to the quantity of the nitrogen source . This leads each species to adopt its own nutritional strategy in order to adapt to the environmental conditions of the ruminal ecosystem. N Z Med J, 2002 Mar 8, 115(1149), 106 - 8 Awareness, knowledge and attitudes of lead maternity carers towards early-onset neonatal group B streptococcal disease; Gosling I et al.; AIM: To determine awareness, knowledge and attitudes of lead maternity carers (LMCs) towards early-onset neonatal group B streptococcus (GBS) infection and its prevention . METHODS: An anonymous, self-administered questionnaire was sent to the 155 practising LMCs in Wellington and Hutt Valley . RESULTS: Completed questionnaires were returned by 84 (54%) LMCs (59 midwives) . 66 (79%) believed perinatal GBS infections were important, 70 (85%) supported antenatal screening, while 68 (81%) were confident of determining risk factors for GBS infection and counselling women . However, less than one-third nominated major risk factors, none identified all five high-risk criteria and only 22 (26%) regularly discussed GBS with clients . When asked to name high-risk criteria, midwives were more likely than doctors to disclose they had incomplete knowledge or not to answer this item (53% vs 20%; p < 0.006) . Of the 48 (57%) LMCs routinely employing GBS prevention strategies, 34 (71%) used culture-based screening, relying mainly upon high-vaginal swabs from the first-trimester . CONCLUSIONS: Despite widespread awareness of perinatal GBS disease, only 57% of surveyed LMCs practised prevention strategies and none completely followed published recommendations . A New Zealand consensus or improved dissemination of local guidelines is required to achieve further reductions in neonatal GBS sepsis. Br Med Bull, 2002, 61, 231 - 45 Treatment of infections due to resistant organisms; Heath PT et al.; Antibiotic resistance remains rare in paediatric community-acquired pneumonia in the UK, but is more common in hospital-acquired pneumonia and in patients with chronic lung diseases . It should also be considered in children arriving from countries with a high prevalence of antibiotic resistance, children with previous heavy antibiotic exposure, those who are immunosuppressed, and those who are not responding to conventional therapy . The most frequent bacterial cause of paediatric pneumonia is Streptococcus pneumoniae and globally there are major concerns about the increasing resistance of this organism to penicillin . Intermediate resistance may be overcome with conventional doses of parenteral penicillin and there is as yet no convincing evidence that intermediate/high level resistance is associated with a worse clinical outcome . Continued vigilance and research is required . The recently introduced pneumococcal conjugate vaccines offer great promise as they are likely to prevent cases of disease due to penicillin-resistant serotypes. Int J Pediatr Otorhinolaryngol, 2002 May 15, 63(3), 235 - 41 Intranasal immunization with lipoteichoic acid and cholera toxin evokes specific pharyngeal IgA and systemic IgG responses and inhibits streptococcal adherence to pharyngeal epithelial cells in mice; Yokoyama Y et al.; OBJECTIVE: Streptococcus (S.) pyogenes is common cause of acute tonsillitis . Lipoteichoic acid (LTA), which is a common constitute of the cell surface of most gram positive bacteria, is known to act as a substance of bacterial site for adherence to epithelium and antiserum to LTA is reported to inhibit bacterial attachment to epithelial cells in vitro . Cholera toxin subunit B (CT-B) is known to be a mucosal adjuvant . The purpose of this study is to investigate whether intranasal immunization with LTA and CT-B may be a possible candidate for vaccine formulation . METHODS: Six-week-old male BALB/c mice were assigned to three experimental groups, mice immunized with LTA and CT-B, with LTA alone and with phosphate buffered saline (PBS) as a control . Immunizations were performed intranasally every 2 days for 2 weeks in every group . At the 21 days after immunization, sera, pharyngeal washings and pharyngeal epithelial cells were taken . The levels of serum IgG and pharyngeal IgA antibodies to LTA were measured by enzyme-linked immunosorbent assay (ELISA) . The adherence rates of S . pyogenes pretreated by pharyngeal washings to pharyngeal epithelial cells from the mice were determined by in vitro adherence assay . RESULTS: The serum anti-LTA IgG antibody levels of either mice immunized with LTA and CT-B or mice immunized with LTA alone were significantly higher than those of mice administered with PBS alone . The pharyngeal anti-LTA IgA antibody levels of the mice immunized with LTA and CT-B were significantly higher than those of either mice with LTA alone or mice with PBS alone . The streptococcal adherence rates to pharyngeal epithelial cells were significantly decreased by pretreatment with pharyngeal washings from the mice immunized with LTA and CT-B as compared with pretreatment with those from either mice with PBS or mice with LTA alone . CONCLUSIONS: These data shows that intranasal immunization with LTA and CT-B evokes a good pharyngeal IgA response as well as systemic IgG response to LTA and inhibits streptococcal adherence to pharyngeal epithelial cells, suggesting that intranasal immunization with LTA and CT-B may be an effective approach to prevent streptococcal tonsillitis. Carbohydr Res, 2002 Apr 30, 337(9), 819 - 25 Isolation of oligosaccharides from a partial-acid hydrolysate of pneumococcal type 3 polysaccharide for use in conjugate vaccines; Lefeber DJ et al.; A series of well-defined oligosaccharide fragments of the capsular polysaccharide of Streptococcus pneumoniae type 3 has been generated . Partial-acid hydrolysis of the capsular polysaccharide, followed by fractionation of the oligosaccharide mixture by Sepharose Q ion-exchange chromatography yielded fragments containing one to seven {-->3)-beta-D-GlcpA-(1-->4)-beta-D-Glcp-(1-->} repeating units . The isolated fragments were analysed for purity by high-pH anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) using an IonPac AS11 column, and their structures were verified by 1H NMR spectroscopy and nano-electrospray mass spectrometry . The oligosaccharides can be used to produce neoglycoprotein vaccines with a defined carbohydrate part. Int J Pharm, 2002 May 15, 238(1-2), 93 - 103 Buccoadhesive erodible disk for treatment of oro-dental infections: design and characterisation; Ali J et al.; Buccoadhesive erodible disks of cetylpyridinium chloride were prepared using different bioadhesive polymers along with excipients like mannitol . The purpose of designing the erodible disk was to obviate the need for removal of exhausted device . The optimized disk containing 5.0 mg of cetylpyridinium chloride, 2.0 mg of magnesium stearate and 6.0 mg of mannitol along with sodium carboxy methyl cellulose DVP and hydroxypropylmethylcellulose K4M in the ratio of 1:3 was found to release the drug for a period of over 6.0 h without getting dislodged . Maximum in vitro drug release was found to be 94.78% in 6.0-h study . In situ release characteristics were evaluated using a 'flow-through assembly', which simulated the conditions of the human buccal cavity . The drug concentrations in the in situ samples were found to be above minimum inhibitory concentration (MIC) of the drug . The bioadhesive performance and the surface pH of the disks were satisfactory . Cetylpyridinium chloride disks were tested against microorganisms commonly found in oro-dental infections namely Candida albicans, Staphylococcus aureus, Escherichia coli and Streptococcus mutans . The disk as well as the in situ samples showed inhibition of growth of microorganisms . Approval was taken from Jamia Hamdard Review Board (Ethical Board) to perform in vivo studies in healthy human volunteers . In vivo evaluation of buccoadhesive disks revealed adequate comfort, taste, and non-irritation and none of the volunteers reported severe dry mouth/severe salivation or heaviness at the place of attachment . Salivary concentrations were maintained above MIC for 8.0 h . Correlation was found between the drug concentration in situ and concentration of drug in saliva collected in healthy human volunteers . The correlation was found to be positive with a correlation coefficient of 0.9596 . It was found to be statistically significant at 5% confidence level (P<0.05). Emerg Infect Dis, 2002 May, 8(5), 479 - 84 Nasopharyngeal carriage of Streptococcus pneumoniae in healthy children: implications for the use of heptavalent pneumococcal conjugate vaccine; Marchisio P et al.; We assessed the prevalence of Streptococcus pneumoniae serotypes in the nasopharynx of healthy children, antimicrobial susceptibility patterns, risk factors for carriage, and the coverage of heptavalent pneumococcal conjugate vaccine . In 2,799 healthy infants and children, the S . pneumoniae carrier rate was 8.6% (serotypes 3, 19F, 23F, 19A, 6B, and 14 were most common) . Most pneumococci (69.4%) were resistant to one or more antimicrobial classes . The rate of penicillin resistance was low (9.1%); macrolide resistance was high (52.1%) . Overall, 63.2% of the isolates belonged to strains covered by the heptavalent pneumococcal vaccine . This percentage was higher in children <2 years old (73.1%) and in those ages 2-5 years (68.9%) . Sinusitis in the previous 3 months was the only risk factor for carrier status; acute otitis media was the only risk factor for the carriage of penicillin-resistant S . pneumoniae . Most isolated strains are covered by the heptavalent conjugate vaccine, especially in the first years of life, suggesting that its use could reduce the incidence of pneumococcal disease. Phytomedicine, 2002 Mar, 9(2), 109 - 16 Medicinal plants in the healing of dry socket in rats: microbiological and microscopic analysis; de Melo Junior EJ et al.; The effectiveness of medicinal herbs as antimicrobial agents was tested on isolated microorganisms from an induced alveolitis and on alveolitis in rats . Sixteen ethanolic extracts from plants were prepared and tested . The plant materials were selected from ethnobotanic data and the best result was obtained with Schinus terebinthifolius Raddi . The activity on Enterococcus, Bacillus corineforme, Streptococcus viridans and S . beta-hemolytic was better than the one presented by the antibiotic currently used for the treatment of alveolitis . The extract of Schinus terebinthifolius Raddi has shown good wound-healing activity by histological analysis. Dev Med Child Neurol, 2002 Apr, 44(4), 273 - 7 Immune mediated chorea encephalopathy syndrome in childhood; Hartley LM et al.; We report four previously healthy female children, aged between 3 and 8 years, who presented with encephalopathy and an extrapyramidal movement disorder (chorea n=4, rigidity n=2, oculogyric crisis n=2) . In addition, an acute behavioural disturbance occurred in two patients and mutism in two others . Seizures heralded the onset of the illness in three patients . Acute MRI was either normal or initially normal with later generalized cerebral atrophy . All infective (including streptococcus), biochemical, and metabolic investigations were normal, although all four patients had oligoclonal bands in the (CSF) but not the serum, indicating intrathecal immunoglobulin synthesis . All four children made an apparently full recovery within four months of the onset.We suggest that these patients represent an immune-mediated movement disorder and encephalopathy syndrome. Am J Epidemiol, 2002 May 15, 155(10), 949 - 57 Association of sexual activity with colonization and vaginal acquisition of group B Streptococcus in nonpregnant women; Meyn LA et al.; In a longitudinal cohort study of 1,248 nonpregnant young women recruited from three Pittsburgh, Pennsylvania, health clinics in 1998-2000, the authors investigated risk factors associated with vaginal acquisition of group B Streptococcus (GBS) . Rectal and vaginal swabs for GBS culture and demographic and behavioral interview data were obtained from the women at enrollment and at three 4-month intervals . Cox proportional hazards models were used to evaluate risk factors for GBS acquisition among the 1,089 women with follow-up data . At enrollment, 365 (29.2%) of the 1,248 study participants were vaginally colonized with GBS . Of 767 women who were GBS-negative at enrollment, 344 (44.9%) acquired vaginal GBS colonization during follow-up . The following factors were independently associated with vaginal acquisition of GBS at the 0.05 significance level: African-American race (hazard ratio (HR) = 1.5, 95% confidence interval (CI): 1.2, 1.9), having multiple sex partners during the past 4 months (HR = 1.7, 95% CI: 1.1, 2.5), having frequent sexual intercourse during the past 4 months (HR = 1.5, 95% CI: 1.1, 2.2), and having sexual intercourse within the 5 days prior to the follow-up visit (HR = 1.6, 95% CI: 1.3, 2.0) . These results show that sexual activity is an important risk factor for vaginal acquisition of GBS. Mol Microbiol, 2002 May, 44(3), 877 - 87 A hypermutator phenotype attenuates the virulence of Listeria monocytogenes in a mouse model; Merino D et al.; The integrity of the genetic material of bacteria is guaranteed by a set of distinct repair mechanisms . The participation of these repair systems in bacterial pathogenicity has been addressed only recently . Here, we study for the first time the participation in virulence of the MutSL mismatch repair system of Listeria monocytogenes . The mutS and mutL genes, which are contiguous in the L . monocytogenes chromosome, were identified after in silico analysis . The deduced MutS shares 62% identity with MutS of Bacillus subtilis and 50% identity with HexA, its homologue in Streptococcus pneumoniae; MutL shares 59% identity with MutL of B . subtilis and 47% identity with HexB of S . pneumoniae . Functional analysis of the mutSL locus was studied by constructing a double knock-out mutant . We showed that the deletion DeltamutSL induces: (i) a 100- to 1000-fold increase in the spontaneous mutation rate; and (ii) a 10- to 15-fold increase in the frequency of transduction, thus demonstrating the role of mutSL of L . monocytogenes in both mismatch repair and homologous recombination . We found that the deletion DeltamutSL moderately affected bacterial virulence, with a 1-log increase in the lethal dose 50% (LD50) in the mouse . Strikingly, repeated passages of the mutant strain in mice reduced virulence further . Competition assays between wild-type and mutant strains showed that the deletion DeltamutSL reduced the capacity of L . monocytogenes to survive and multiply in mice . These results thus demonstrate that, for the intracellular pathogen L . monocytogenes, a hypermutator phenotype is more deleterious than profitable to its virulence. J Infect Dis, 2002 May 15, 185(10), 1517 - 20 Epub 2002 Apr 23. Variant mannose-binding lectin alleles are not associated with susceptibility to or outcome of invasive pneumococcal infection in randomly included patients; Kronborg G et al.; Invasive pneumococcal disease is a serious infection that primarily affects very young children and elderly or immunocompromised individuals but also affects previously healthy people . Variant mannose-binding lectin (MBL) alleles are associated with recurrent infections and may be a risk factor for pneumococcal infections . To assess the influence of MBL genotypes on the course and outcome of invasive pneumococcal disease, clinical data for 141 adult patients were collected prospectively and their genotypes were determined . All patients included had positive blood cultures for Streptococcus pneumoniae . The distribution of variant MBL alleles related to low MBL serum concentrations was similar among the patients and healthy individuals, and MBL genotype was not associated with infection outcome . Thus, in a random adult population with invasive pneumococcal infection, MBL does not seem to play a role in the pathophysiology, in contrast to earlier observations in patients with other concomitant immune abnormalities. J Biol Chem, 2002 Aug 2, 277(31), 28287 - 97 Epub 2002 May 03. Mechanism of hyaluronan degradation by Streptococcus pneumoniae hyaluronate lyase . Structures of complexes with the substrate; Jedrzejas MJ et al.; Hyaluronate lyase enzymes degrade hyaluronan, the main polysaccharide component of the host connective tissues, predominantly into unsaturated disaccharide units, thereby destroying the normal connective tissue structure and exposing the tissue cells to various endo- and exogenous factors, including bacterial toxins . The crystal structures of Streptococcus pneumoniae hyaluronate lyase with tetra- and hexasaccharide hyaluronan substrates bound in the active site were determined at 1.52- and 2.0-A resolution, respectively . Hexasaccharide is the longest substrate segment that binds entirely within the active site of these enzymes . The enzyme residues responsible for substrate binding, positioning, catalysis, and product release were thereby identified and their specific roles characterized . The involvement of three residues in catalysis, Asn(349), His(399), and Tyr(408), is confirmed, and the details of proton acceptance and donation within the catalytic machinery are described . The mechanism of processivity of the enzyme is analyzed . The flexibility (allosteric) behavior of the enzyme may be understood in terms of the results of flexibility analysis of this protein, which identified two modes of motion that are also proposed to be involved in the hyaluronan degradation process . The first motion describes an opening and closing of the catalytic cleft located between the alpha- and beta-domains . The second motion demonstrates the mobility of a binding cleft, which may facilitate the binding of the negatively charged hyaluronan to the enzyme. Hybrid Hybridomics, 2002 Feb, 21(1), 19 - 24 Differential V gene expression detected in the immune response to Streptococcus pneumoniae capsular polysaccharide between elderly and young adults; Smithson SL et al.; Streptococcus pneumoniae is one of the major causative agents of respiratory infections in the elderly population . The 23-valent pneumococcal polysaccharide vaccine is recommended for use in this age group . However, research has indicated that the protective efficacy of the vaccine declines with age . Although similar levels of antibody induction are seen in both young and elderly adults, following immunization with this vaccine, recent studies have indicated that the elderly possess antibodies with lower opsonophagocytic activity and avidity than young adults . We investigated whether a shift in V(H) gene usage may be responsible for this observation . To this end we utilized anti-idiotypic determinants to detect V(H)1 and V(H)3 gene usage by antibodies to pneumococcal capsular polysaccharides in both young and elderly subjects by enzyme-linked immunosorbent assay (ELISA) . We found no significant difference in V(H)3 idiotypic expression in antibody responses to capsular polysaccharide from serotype 14 (PPS14) . In response to PPS14 a significant higher level of V(H)1 idiotypic expressing antibodies was detected in the elderly as compared with young adults . V(H)1 idiotypic expression in response to capsular polysaccharide from serotype 4 (PPS4) was identical in young and elderly individuals . V(H)3 idiotypic expression in the elderly response to PPS4 was significantly lower than that seen in young individuals . These patterns of idiotypic expression are discussed in relation to recent studies of functional activity of pneumococcal reactive antibodies from young and aged humans. J Am Dent Assoc, 2002 Apr, 133(4), 435 - 41; quiz 492-3 How xylitol-containing products affect cariogenic bacteria; Roberts MC et al.; BACKGROUND: The authors examined the effect of xylitol, a naturally occurring sweetener, on levels of Streptococcus mutans and S . sobrinus . They also investigated xylitol's mechanism of action . METHODS: The authors compared cariogenic bacteria levels before and after exposure to xylitol products in children and adults . In the first study, 187 children received xylitol-containing snacks in school for four weeks . In the second study, two adults received xylitol candy for four weeks . Unstimulated saliva samples were taken from all subjects . Gingival samples also were taken from the adults . The authors plated the samples on selective microbiological media . Individual isolates were plated on media with varying concentrations of xylitol, and were identified using specific DNA probes . Genetic relatedness was determined via pulse-field gel electrophoresis . RESULTS: The children's salivary S . mutans levels remained stable before and after xylitol exposure . Further analysis of the S . mutans isolates was conducted for seven children . Bacteria from five of these children grew with 10 percent or less xylitol at baseline, while the bacteria from all seven children grew with 15 percent xylitol after exposure to the xylitol-containing snacks, suggesting that the S . mutans increased in tolerance to xylitol during exposure . Six children had isolates with the same genotype at both time points . S . mutans and S . sobrinus levels were reduced in one of the adults as a result of xylitol exposure, and the bacterial isolates became more xylitol tolerant . In the second adult, S . mutans and S . sobrinus levels increased, while the subject maintained the same proportion of susceptible and tolerant strains as that at baseline . CONCLUSIONS: Overall, consumption of xylitol-containing snacks and candy did not reduce S . mutans levels . However, bacteria from five children and one adult became more xylitol tolerant . CLINICAL IMPLICATIONS: These results provide a basis on which xylitol-containing products can be recommended and xylitol's mechanism of action can be explained to patients. Pediatr Dent, 2002 Mar-Apr, 24(2), 103 - 8 Preventing the transfer of Streptococcus mutans from primary molars to permanent first molars using chlorhexidine; Alaki SM et al.; PURPOSE: The purpose of this study was to determine if the application of 1% chlorhexidine-containing wax on primary molars during the period of eruption of the first permanent molars could prevent the transfer of certain oral flora, namely Streptococcus mutans, to the permanent molars . METHODS: Fourteen children with a mean age of 6.5 years (7 males and 7 females) were assigned into two groups: a chlorhexidine group (n=9) in which 1% chlorhexidine-containing wax was painted on primary molars on one side of the mouth; and a placebo wax group (n=5) in which a similar wax, but without chlorhexidine, was painted on primary molars on the other side of the mouth . Baseline saliva samples and pooled plaque samples from the primary molars on both sides of the dentition were obtained from the two treatment groups . Following treatment, plaque samples from the occlusal fissures of the first permanent molars on both sides of the dentition were obtained . The levels of S.mutans and other members of the oral flora on the treated sides (chlorhexidine or placebo) were compared with those on the untreated sides . RESULTS: The results showed that the proportions of S.mutans to S.sanguinis were significantly lower in the chlorhexidine-treated sides compared to the untreated (P=0.04) and in the chlorhexidine-treated patients compared to placebo (P=0.029) . CONCLUSIONS: Since lower mutans to sanguinis ratios have been associated with lower caries experience, treating primary molars with 1% chlorhexidine wax during eruption of permanent first molars may be a simple means for shifting the fissure flora of the permanent molars towards a more favorable balance. J Med Microbiol, 2002 May, 51(5), 443 - 7 PCR detection of Streptococcus mutans and S . sobrinus in dental plaque samples from Japanese pre-school children; Okada M et al.; Streptococcus mutans and S . sobrinus are associated with the development of dental caries . These bacteria were detected by PCR and then their presence was compared with the incidence of dental caries in 77 Japanese pre-school children . Plaque samples were collected from all erupted tooth sites in the subjects, aged 3-5 years old and each with primary dentition, with a sterile toothbrush . A dental examination was performed for dmft (decayed, missing, filled, total) with the WHO caries diagnostic criteria . In all subjects, the prevalence of S . mutans and S . sobrinus was 72.8% and 61.1%, respectively; 19 (24.7%) were positive for S . mutans alone, 10 (13.0%) were positive for S . sobrinus alone, 37 (48.1%) were positive for both S . mutans and S . sobrinus, and 11 (14.3%) were negative for both S . mutans and S . sobrinus . The dmft scores of children positive for both S . mutans and S . sobrinus were significantly higher than those positive for S . mutans alone . These results indicate that children harbouring both S . mutans and S . sobrinus have a significantly higher incidence of dental caries than those with S . mutans alone. Microbiology, 2002 May, 148(Pt 5), 1493 - 9 tRNA gene clusters at the 3' end of rRNA operons are specific to virulent subgroups of Streptococcus agalactiae strains, as demonstrated by molecular differential analysis at the population level; Rolland K et al.; The aim of this work was to characterize a 2.4 kb randomly amplified polymorphic DNA (RAPD) fragment described as a marker for a phylogenetic group of Streptococcus agalactiae strains significantly associated with neonatal meningitis . This fragment was analysed by cloning and sequencing, and showed that two types of tRNA gene cluster flank the 3' end of the rRNA operons in S . agalactiae strains . Both types of tRNA gene cluster act as markers for phylogenetic subgroups of strains within the species . One type could be used to distinguish two of the three virulent intraspecies subgroups to which most of the S . agalactiae strains able to invade the central nervous system of neonates belong . This raises the possibility that there is a link between these tRNA genes and the virulence of the bacterium . Based on this analysis, PCR primers were designed to determine whether S . agalactiae strains are likely to belong to lineages of organisms in which most of the highly virulent strains isolated from cerebrospinal fluid cluster . In addition, this work demonstrated that RAPD can be used to detect novel particularities within intraspecies variants of pathogens. Microbiology, 2002 May, 148(Pt 5), 1483 - 91 In vivo characterization of the psa genes from Streptococcus pneumoniae in multiple models of infection; Marra A et al.; Differential fluorescence induction technology was used to identify promoters of Streptococcus pneumoniae genes that are expressed during lung infection of the mouse . Among the promoter clones that were identified multiple times was the psa promoter, which drives expression of the psaBCA operon . These genes have been identified previously and shown to encode a manganese permease system as well as play a role in the virulence of this organism . Mutations in psaB, psaC or psaA result in growth limitation in low manganese . The expression of the psa operon was examined in vivo and the virulence of deletion mutants of psaB, psaC, psaA and psaBCA was assessed in four different animal models of infection . The psa promoter was induced more than ten-fold in vivo using an intraperitoneal chamber implant model . The psaB, psaC and psaA mutants were completely attenuated in systemic, respiratory tract and otitis media infections . In addition, these mutants were unable to grow in an implanted peritoneal chamber, but growth was restored by the addition of manganese to the chambers. Ophthalmology, 2002 May, 109(5), 985 - 91 Delayed-onset bleb-associated endophthalmitis: clinical features and visual acuity outcomes; Song A et al.; OBJECTIVE: To investigate clinical factors, causative organisms, treatments, and visual acuity and intraocular pressure outcomes associated with delayed-onset, bleb-associated endophthalmitis . DESIGN: Retrospective, noncomparative, consecutive case series . PARTICIPANTS: All patients treated for bleb-associated endophthalmitis at Bascom Palmer Eye Institute between January 1, 1996, and July 1, 2001 . All patients had prior glaucoma filtering surgery . Patients with inadvertent functioning blebs after cataract extraction were excluded . MAIN OUTCOME MEASURES: Visual acuity outcomes and intraocular pressure control after endophthalmitis . RESULTS: An antifibrotic agent was used in 40 (82%) of the 49 eyes identified, including mitomycin-C in 33 (67%) and 5-fluorouracil (5-FU) in 7 (14%) . The mean interval between the initial filtering surgery and endophthalmitis diagnosis was 5.0 years (range, 0.7-12.2 years) . The mean follow-up time after treatment for endophthalmitis was 6.9 months (range, 1-60 months) . As recorded in the medical record, potential risk factors and clinical features among the study population included history of bleb leak in 13 (27%) eyes, bleb manipulations in 15 (31%) (needling in 3 {6%}, compression sutures in 2 {4%}, laser suture lysis in 6 {12%}, bleb revision in 5 {10%}, and autologous blood injection in 2 {4%}), bleb defects in 6 (12%), inferior bleb location 6 (12%), and nasolacrimal duct obstruction in 1 (2%) . The most common causative organisms were Streptococcus species in 15 eyes (31%) and Staphylococcus species in 11 eyes (22%) . Final visual acuities in the vitrectomy group (n = 22) versus the initial tap group (n = 26) were as follows: > or = 20/40 (5% versus 15%), 20/50 to 20/400 (32% versus 54%), and < 5/200 (64% versus 31%) . Eleven (22%) patients eventually underwent enucleation or evisceration secondary to pain and/or poor vision (light perception to no light perception) . In 4 (11%) of the 38 eyes not enucleated, intraocular pressures were poorly controlled at last follow-up (>21 mmHg) after treatment of endophthalmitis . CONCLUSIONS: Streptococcus species and Staphylococcus species were the most common causative organisms in the current series of patients with delayed-onset bleb-associated endophthalmitis . Despite successful treatment of the infection, visual outcomes are generally poor. Eur J Biochem, 2002 Apr, 269(8), 2232 - 7 Bass hepcidin is a novel antimicrobial peptide induced by bacterial challenge; Shike H et al.; We report the isolation of a novel antimicrobial peptide, bass hepcidin, from the gill of hybrid striped bass, white bass (Morone chrysops) x striped bass (M . saxatilis) . After the intraperitoneal injection of Micrococcus luteus and Escherichia coli, the peptide was purified from HPLC fractions with antimicrobial activity against Escherichia coli . Sequencing by Edman degradation revealed a 21-residue peptide (GCRFCCNCCPNMSGCGVCCRF) with eight putative cysteines . Molecular mass measurements of the native peptide and the reduced and alkylated peptide confirmed the sequence with four intramolecular disulfide bridges . Peptide sequence homology to human hepcidin and other predicted hepcidins, indicated that the peptide is a new member of the hepcidin family . Nucleotide sequences for cDNA and genomic DNA were determined for white bass . A predicted prepropeptide (85 amino acids) consists of three domains: a signal peptide (24 amino acids), prodomain (40 amino acids) and a mature peptide (21 amino acids) . The gene has two introns and three exons . A TATA box and several consensus-binding motifs for transcription factors including C/EBP, nuclear factor-kappaB, and hepatocyte nuclear factor were found in the region upstream of the transcriptional start site . In white bass liver, hepcidin gene expression was induced 4500-fold following challenge with the fish pathogen, Streptococcus iniae, while expression levels remained low in all other tissues tested . A novel antimicrobial peptide from the gill, bass hepcidin, is predominantly expressed in the liver and highly inducible by bacterial exposure. Clin Infect Dis, 2002 May 15, 34(10), E50 - 3 Epub 2002 Apr 24. Acute terminal ileitis associated with pneumococcal bacteremia: case report and review of pneumococcal gastrointestinal diseases; Petti CA et al.; In this report, we describe a patient with acute terminal ileitis due to Streptococcus pneumoniae, review 3 previously reported cases of isolated enteritis due to S . pneumoniae, and summarize the English-language literature on primary and secondary pneumococcal gastrointestinal diseases . Various theories have been advanced to explain the pathogenesis of this rare and potentially life-threatening form of pneumococcal infection, but the mechanism by which S . pneumoniae causes gastrointestinal disease is still unknown. Minerva Pediatr, 2002 Apr, 54(2), 161 - 3 Early onset of neonatal sepsis due to group A streptococcus; Casanova-Roman M et al.; Neonatal infections by group A beta-hemolytic streptococcus are very rare in the antibiotic era . There are only a few cases in the first 72 hours after birth . The authors describe a case in which it was confirmed that the bacteria responsible, group A beta-hemolytic streptococcus, had grown in the newborn's blood and in the mother's lochia . The transmission mechanisms are also reviewed. J Clin Microbiol, 2002 May, 40(5), 1851 - 3 Household transmission of Streptococcus pneumoniae among siblings with acute otitis media; Shimada J et al.; Nasopharyngeal transmission of Streptococcus pneumoniae was evaluated among 23 siblings with acute otitis media (AOM) . Restriction fragment length polymorphism revealed that the nasopharyngeal strains were identical between siblings in 12 of 13 clusters of AOM experienced in 11 families . This study demonstrated person-to-person transmission of S . pneumoniae, especially drug-resistant strains, among siblings with AOM. J Clin Microbiol, 2002 May, 40(5), 1805 - 10 Molecular analysis of group A Streptococcus type emm18 isolates temporally associated with acute rheumatic fever outbreaks in Salt Lake City, Utah; Smoot JC et al.; Acute rheumatic fever (ARF) and subsequent rheumatic heart disease are rare but serious sequelae of group A Streptococcus (GAS) infections in most western countries . Salt Lake City (SLC), Utah, and the surrounding intermountain region experienced a resurgence of ARF in 1985 which has persisted . The largest numbers of cases were encountered in 1985-1986 and in 1997-1998 . Organisms with a mucoid colony phenotype when grown on blood agar plates were temporally associated with the higher incidence of ARF . To develop an understanding of the molecular population genetic structure of GAS strains associated with ARF in the SLC region, 964 mucoid and nonmucoid pharyngeal isolates recovered in SLC from 1984 to 1999 were studied by sequencing the emm gene . Isolates with an emm18 allele were further characterized by sequencing the spa, covR, and covS genes . Peak periods of ARF were associated with GAS isolates possessing an emm18 allele encoding the protein found in serotype M18 isolates . Among the serotype M18 isolates, the difference in the number of C repeats produced three size variants . Variation was limited in spa, a gene that encodes a streptococcal protective antigen, and covR and covS, genes that encode a two-component regulatory system that, when inactivated, results in a mucoid phenotype and enhanced virulence in mouse infection models . Pulsed-field gel electrophoresis showed a single restriction profile for serotype M18 organisms isolated during both peak periods of ARF . In SLC, the incidence of ARF coresurged with the occurrence of GAS serotype M18 isolates that have very restricted genetic variation. Braz J Infect Dis, 2001 Dec, 5(6), 305 - 12 Susceptibility of S . pneumoniae to various antibiotics aong strains isolated from patients and healthy carriers in different regions of Brazil(1999-2000); Rossi F et al.; Resistance of microbes to commonly used antibiotics became a major concern at the end of the last century . Because Streptococcus pneumoniae is the most common pathogen in respiratory infections, we conducted microbiological assessment of drug susceptibility patterns among strains collected from two different population groups: 1) adult and pediatric patients (375 isolates) with different infections, and 2) healthy children in day care centers (<5 years old; 350 isolates) . High level resistance to penicillin was not identified in either group . Intermediate resistance levels were similar in both groups (adults: 9.9%; children: 9.2%) . The Central West region of Brazil tended to have lower susceptibility of S . Pneumoniae from infected adults and children to penicillin (81% vs . 93% in the South and 90% in the Southeast), tetracycline (64% vs . 80% and 76%), and trimethoprim/sulfamethoxazole (14% vs . 34%) . Susceptibility was similar among strains from nasal cultures of healthy children tested in each of 4 regions of Brazil . All isolates were susceptible to cefaclor, cefotaxime and amoxacillin/clavulanate . This study, in two distinct populations, allowed characterization of local microbiological resistance patterns . This data is expected to be of use in guiding empiric therapy in the different regions of Brazil. Braz J Infect Dis, 2001 Dec, 5(6), 294 - 304 Epub 2003 Feb 21. Antimicrobial resistance in respiratory pathogens isolated in Brazil during 1999-2000; Critchley IA et al.; The in vitro antimicrobial susceptibility of the respiratory pathogens Streptococcus Pneumoniae, Hemophilus influenzae, and Moraxella catarrhalis to commonly tested and prescribed agents was investigated during 1999-2000 and compared with results obtained during a previous 1997-1998 study . Of 448 isolates of S . Pneumoniae collected and tested in 1999-2000, 77.2% were susceptible, 19.9% were intermediate, and 2.9% were resistant to penicillin, demonstrating that there were no major changes in susceptibility to penicillin from 1997-1998 (77.1% susceptible, 18.7% intermediate, 4.2% resistant) . All S . Pneumoniae isolates from 1999-2000 were susceptible to levofloxacin and vancomycin and >90% were susceptible to the B-lactams (amoxicillin-clavulanate, ceftriaxone, and cefuroxime) and macrolides (axithyromycin and clarithromycin), showing that susceptibility to these agents also remained unchanged since 1997-1998 . The most notable increase in resistance between the two studies was demonstrated by trimethoprim-sulfamethoxazole, which increased from 23.4% to 38.6% . Penicillin resistance correlated with resistance to B-lactams, macrolides, and trimethoprim-sulfamethoxazole in both studies . In H . influenzae, the prevalence of B-lactamase-producing isolates remained unchanged (10.6% in 1999-2000; 11.0% in 1997-1998) . All H . influenzae isolates were susceptible to levofloxacine, ceftriaxone, cefuroxime, and azithromycin, and showed no change between the two studies . Trimethoprim-sulfamethoxazole resistance was present in 40.1% of isolates in 1999-2000, and in 45.2% in 1997-1998 . In M . catarrhalis, the prevalence of B-lactamase-producing isolates was unchanged (97.9% in 1999-2000;98.0% in 1997-1998) . The most active agents against M . catarrhalis were azithromycin (MIC(90),< or = 0.03 microg/ml) and levofloxacin (MIC(90),< or = 0.03 microg/ml) . Overall, these results suggest that, in Brazil, between 1999-2000 and 1997-1998, there have been no significant changes in the susceptibility of respiratory pathogens to any of the commonly tested and prescribed agents with the exception of trimethoprim-sulfamethoxazole for S . Pneumoniae. Arch Pediatr Adolesc Med, 2002 May, 156(5), 469 - 72 Low risk of bacteremia in children with febrile seizures; Shah SS et al.; OBJECTIVE: To evaluate the risk of bacteremia in children with febrile seizures treated as outpatients . METHODS: A retrospective cohort study was performed involving 379 children aged 2 to 24 months presenting to an urban tertiary care children's hospital emergency department with a febrile seizure between February 1, 1993, and May 31, 1996 . RESULTS: The mean patient age was 15.9 months, and 217 (57%) were male . In 40 patients (10.6%), the use of oral antibiotics before initial emergency department evaluation was reported . Bacteremia occurred in 8 (2.1%) of 379 children studied . None of the children with bacteremia had received previous antibiotics . The causative organisms were Streptococcus pneumoniae in 7 cases and group A Streptococcus in 1 case . There were 5 contaminated cultures (1.3%) . Although 2 of the 8 children with bacteremia ultimately required admission, there were no serious adverse outcomes . Six of 7 episodes of S pneumoniae bacteremia were caused by serotypes included in the pneumococcal conjugate vaccine, which was not available at the time of this study . CONCLUSIONS: Children 2 to 24 months of age with febrile seizures are at similar risk for occult bacteremia as those with fever alone . Widespread use of the pneumococcal conjugate vaccine may further decrease the incidence of bacteremia in this population. J Tenn Dent Assoc, 2002 Spring, 82(1), 19 - 22 Streptococcus mutans levels and caries prevalence in low-income schoolchildren; Seibert W et al.; Previous studies have shown that persons having high Streptococcus mutans levels in the saliva are "at risk" for dental caries . Most investigators agree, that if high levels of S . mutans were identified early in the life of at-risk children, dental decay could be reduced or eliminated through intervention . The purpose of this study is to show an association between S . mutans levels and caries prevalence in a sample of elementary school children . The study group consisted of 242 school children, ages 5-13 years . The subjects were divided into two age groups, 5-8 years and 9-13 years . Approximately 59 percent were African Americans . The sample of 242 children were equally females and males, 50 percent in each group . The Dentocult SM Test was used to make S . mutans determinations . The df-t index was used to determine the number of decayed and filled teeth of children ages 5-8 years; the DMF-T Index estimated the number of decayed, missing or filled teeth of children ages 9-13 years . Dental caries were found in 58 percent of the children (mean = 2.67, and range of 1-11) . Approximately 47 percent of the children with caries had high S . mutans levels (100K-1M) . Females had higher S . mutans levels than males in the 9-13 age group, p < .05 . Analysis of Variance Test indicated that S . mutans levels for older females (ages 9-13) were significantly higher than those observed in males the same age (p < .01) . This trend was not observed in younger children, ages 5-8 years . In addition, no significant difference or interaction was noted by sex for S . mutans levels and decayed or filled teeth (df-t) for younger children . We conclude that high levels of Streptococcus mutans are related to increased number of decayed teeth and conversely, low Streptococcus mutans levels are related to fewer dental caries . This study was supported in part by Colgate-Palmolive Company and the National Dental Association Foundation, Inc. Curr Opin Infect Dis, 2001 Apr, 14(2), 173 - 9 Streptococcus pneumoniae respiratory tract infections; Klugman KP et al.; This review describes recent contributions to our understanding of pneumococcal pneumonia . Two genes have been described that encode enzymes involved with the biosynthesis of muropeptides . These enzymes may be novel antibiotic targets . The clinical impact of increasing antibiotic resistance on the treatment of pneumonia is the particular focus of the review . As resistant strains are more commonly associated with severe infections in patients with underlying disease, the interpretation of an association of resistance with poor clinical outcome is complicated. J Fam Pract, 2002 Apr, 51(4), 339 - 44 Effect on antibiotic prescribing of repeated clinical prompts to use a sore throat score: lessons from a failed community intervention study; McIsaac WJ et al.; OBJECTIVES: Infections with group A streptococcus (GAS) occur in 10% to 20% of patients with sore throats, whereas antibiotics are prescribed 50% of the time . Clinical scoring rules can more accurately predict the likelihood of GAS infection, but whether family physicians will adopt such approaches is unclear . This study sought to determine whether repeated clinical prompts to use a scoring approach could help family physicians lower antibiotic use in patients with a sore throat . STUDY DESIGN: Randomized trial in which physicians were assigned to use either (1) chart stickers that prompted them to calculate a score based on clinical findings and provided management recommendations linked to score totals or (2) a clinical checklist . POPULATION: Ninety-seven family physicians in Ontario, Canada, assessed 621 children and adults with sore throat and obtained a throat swab for culture . OUTCOMES MEASURED: (1) Unnecessary antibiotic prescriptions given to patients with a negative throat culture and (2) overall antibiotic use . RESULTS: There were no differences between the control and intervention group in unnecessary antibiotic prescriptions (16.1% vs 20.4%, respectively, P =.29) or overall antibiotic use (27.9% vs 28.1%, P =.97) . However, a number of physicians dropped out of the study; as a result, the characteristics of the physicians in the 2 groups were dissimilar in factors related to prescribing . After adjusting for these differences and patient clustering by physician, the odds ratio for the effect of the intervention on unnecessary antibiotic prescriptions was 0.76 (95% confidence interval {CI} = 0.42, 1.40) and 0.57 for overall antibiotic use (95% CI = 0.27, 1.17) . CONCLUSIONS: Chart prompts during clinical encounters to use a clinical score in the assessment of patients with a sore throat did not reduce unnecessary antibiotic prescribing by family physicians . The problems encountered in conducting this community-based intervention trial are discussed in relation to the negative result. Am J Health Syst Pharm, 2002 Apr 15, 59(8 Suppl 3), S7 - 11 Role of NCCLS in antimicrobial susceptibility testing and monitoring; Ginocchio CC; The role of NCCLS (formerly known as the National Committee for Clinical Laboratory Standards) in establishing guidelines for antimicrobial susceptibility testing, NCCLS's consensus-building process, and new interpretive criteria for antimicrobial susceptibility testing for 2002 are described . When revising and developing new guidelines, NCCLS uses an extensive process to reach consensus, while considering the clinical relevance, cost, and other practical implications of the proposed guidelines . NCCLS groups antimicrobials for susceptibility testing and reporting on the basis of their clinical efficacy, known patterns of microbial resistance, strategies to minimize the emergence of resistance, consensus recommendations, and cost to avoid unnecessary testing . NCCLS guidelines address quality control issues and current methodologies, such as conventional disk diffusion and microbroth dilution tests . In addition, new testing methods for the detection and confirmation of special resistance mechanisms (e.g., extended-spectrum beta-lactamase production) are recommended . In 2002, the minimum inhibitory concentration breakpoints for resistance and susceptibility of Streptococcus pneumoniae to cefotaxime and ceftriaxone in nonmeningitis infection were increased to more accurately predict clinical outcomes . Implementation of new NCCLS guidelines requires the education and collaboration of the laboratory, pharmacy, and medical staff . The NCCLS consensus-building process provides clinicians with clinically relevant and cost-effective strategies for antimicrobial susceptibility testing and reporting, guidelines and criteria for interpreting susceptibility test results, and guidelines for detecting emerging antimicrobial resistance . The use of specialized testing methods for detecting and confirming unusual or difficult-to-identify resistance mechanisms can improve the accuracy of reporting of resistance and avoid therapeutic failures . The implementation of new NCCLS guidelines requires collaboration and education of members of various institutional departments. Appl Environ Microbiol, 2002 May, 68(5), 2382 - 90 Analysis of Streptococcus mutans proteins modulated by culture under acidic conditions; Wilkins JC et al.; Streptococcus mutans, a major etiological agent of dental caries, causes demineralization of the tooth tissue due to the formation of acids from dietary carbohydrates . Dominant among the virulence determinants of this organism are aciduricity and acidogenicity, the abilities to grow at low pH and to produce acid, respectively . The mechanisms underlying the ability of S . mutans to survive and proliferate at low pH are currently under investigation . In this study we cultured S . mutans at pH 5.2 or 7.0 and extracted soluble cellular proteins . These were analyzed using high-resolution two-dimensional gel electrophoresis, and replicate maps of proteins expressed under each of the two conditions were generated . Proteins with modulated expression at low pH, as judged by a change in the relative integrated optical density, were excised and digested with trypsin by using an in-gel protocol . Tryptic digests were analyzed using matrix-assisted laser desorption ionization mass spectrometry to generate peptide mass fingerprints, and these were used to assign putative functions according to their homology with the translated sequences in the S . mutans genomic database . Thirty individual proteins exhibited altered expression as a result of culture of S . mutans at low pH . Up-regulated proteins (n = 18) included neutral endopeptidase, phosphoglucomutase, 60-kDa chaperonin, cell division proteins, enolase, lactate dehydrogenase, fructose bisphosphate aldolase, acetoin reductase, superoxide dismutase, and lactoylglutathione lyase . Proteins down-regulated at pH 5.2 (n = 12) included protein translation elongation factors G, Tu, and Ts, DnaK, small-subunit ribosomal protein S1P, large-subunit ribosomal protein L12P, and components of both phosphoenolpyruvate:protein phosphotransferase and multiple sugar binding transport systems . The identification of proteins differentially expressed following growth at low pH provides new information regarding the mechanisms of survival and has identified new target genes for mutagenesis studies to further assess their physiological significance. Obstet Gynecol, 2002 May, 99(5 Pt 2), 906 - 9 Primary psoas abscess complicating a normal vaginal delivery; Shahabi S et al.; BACKGROUND: Psoas abscess is a rare and potentially dangerous complication of normal delivery . CASE: We describe a case of primary psoas abscess after normal vaginal delivery . A young woman presented with fever, left back pain, left lower abdominal pain, and hip pain starting on postpartum day 2 . Computed tomography demonstrated a large retroperitoneal collection . Aspiration drainage of the abscess under computed tomography guidance isolated Streptococcus viridans, which responded to antibiotic therapy and percutaneous drainage with complete resolution . CONCLUSION:A high index of suspicion is necessary for diagnosis of psoas abscess, which should be considered in postpartum patients with pyrexia, back and hip pain, and a normal neurologic examination . Computed tomography is effective for diagnosis and allows percutaneous drainage of the abscess. Kansenshogaku Zasshi, 2002 Mar, 76(3), 174 - 9 {A three-year review of acute respiratory tract infections caused by Streptococcus milleri group}; Fujiki R et al.; The objective of our study is to understand the clinical features of patients with acute respiratory tract infection associated with Streptococcus milleri group (SMG) . Fifteen patients with SMG respiratory tract infection visited our hospital from July, 1997 through May, 2000 . There were seven cases of pneumonia, two pulmonary abscess, three thoracic empyema and three acute bronchitis . The mean age of the patients was 57.8 years (range 16-87), twelve were males, and seven were smokers . The moderately to severe underlying diseases existed in thirteen patients (86.7%) and included the following: respiratory diseases (20.0%), history of the esophageal or gastric surgery (26.7%), central nerve system diseases (13.3%), alcohol intake (60.0%), hepatitis and pancreatitis (33.3%), diabetes mellitus (13.3%) and malignancy (6.7%) . The species of SMG detected were as follows: S . constellatus, 8, S . anginosus, 6 and S . intermedius, 1 . Anaerobic organism and other microorganisms were detected in five patients . A patient with SMG nosocominal pneumonia who previously had thoracic surgery for esophageal cancer died . Antibiotics therapy with carbapenem or combination therapy, drainage and no surgery, were successful in 14 of the 15 cases (93.3%) . The number of intermediately or complete resistant strains against penicillin G, ampicillin and cefmetazole were 5 (33.3%), 8 (53.3%) and 12 (80.0%), respectively in this series . Recently, it is seemed that acute respiratory tract infections caused by SMG are increasing in the patients with moderately to severe underlying diseases, and several clinical strains of SMG are acquiring a tolerance to antibiotics. J Cataract Refract Surg, 2002 Mar, 28(3), 550 - 2 Pneumococcal keratitis at the flap interface after laser in situ keratomileusis; Ramirez M et al.; A 28-year-old woman had uneventful laser in situ keratomileusis in the right eye . Six days postoperatively, she reported ocular pain and a large corneal stromal infiltrate was observed at the flap interface . A second surgery including lifting and excising the flap and scraping the stromal bed was performed . Topical antibiotics were prescribed . A bacterial culture revealed Streptococcus pneumoniae . The keratitis responded well to topical vancomycin . Twelve days after the second surgery, the stromal infiltrate had regressed, the hypopyon had resolved, and visual acuity was hand movements at 0.5 m. Mol Microbiol, 2002 Apr, 44(2), 431 - 48 Characterization of the dihydrolipoamide dehydrogenase from Streptococcus pneumoniae and its role in pneumococcal infection; Smith AW et al.; In the present study, we have characterized the dihydrolipoamide dehydrogenase (DLDH) of Strepto-coccus pneumoniae and its role during pneumococcal infection . We have also demonstrated that a lack of DLDH results in a deficiency in alpha-galactoside metabolism and galactose transport . DLDH is an enzyme that is classically involved in the three-step conversion of 2-oxo acids to their respective acyl-CoA derivatives, but DLDH has also been shown to have other functions . The dldh gene was virtually identical in three pneumococcal strains examined . Besides the functional domains and motifs associated with this enzyme, analysis of the pneumococcal dldh gene sequence revealed the presence of an N-terminal lipoyl domain . DLDH-negative bacteria totally lacked DLDH activity, indicating that this gene encodes the only DLDH in S . pneumoniae . These DLDH-negative bacteria grew normally in vitro but were avirulent in sepsis and lung infection models in mice, indicating that DLDH activity is necessary for the survival of pneumococci within the host . The lack of virulence was not associated with a loss of 2-oxo acid dehydrogenase activity, as the wild-type pneumococcal strains did not contain activity of any of the known 2-oxo acid enzyme complexes . Instead, studies of carbohydrate utilization demonstrated that the DLDH-negative bacteria were impaired for alpha-galactoside and galactose metabolism . The DLDH mutants lost their ability to oxidize or grow with galactose or melibiose as sole carbon source and showed reduced oxidation and growth on raffinose or stachyose . The bacteria had an 85% reduction in alpha-galactosidase activity and showed virtually no transport of galactose into the cells, which can explain these phenotypic changes . The DLDH-negative bacteria produced only 50% of normal capsular polysaccharide, a phenotype that may be associated with impaired carbohydrate metabolism. J Cutan Pathol, 2002 Mar, 29(3), 168 - 72 Epidemiology and microbiology of cellulitis and bacterial soft tissue infection during HIV disease: a 10-year survey; Manfredi R et al.; BACKGROUND: Cellulitis and soft tissue infection are underestimated complications of HIV disease . PATIENTS AND METHODS: Sixty-seven bacteriologically proven consecutive episodes were identified among 2221 HIV-infected patients hospitalized in a 10-year period, and assessed according to several epidemiological, microbiological and clinical variables . RESULTS: Staphylococcus aureus was the most frequently cultured pathogen (50% of 92 isolates), followed by Pseudomonas spp., Escherichia coli and Streptococcus pyogenes; a polymicrobial infection was present in 38.1% of episodes . Drug addiction (p < 0.003) and male gender (p < 0.04) were significantly associated with the occurrence of these complications, which were community-acquired in 83.6% of cases . While a remarkable variation in the severity of underlying immunodeficiency was shown, hematogenous dissemination occurred in 25.4% of episodes, and proved significantly related to a low CD4+ lymphocyte count, and neutropenia . A 21.7% methicillin-resistance rate was shown among S . aureus isolates . All episodes were favorably treated in 5-16 days, in over 60% of cases with associated beta-lactam-aminglycoside antibiotics; a recurrence of staphylococcal cellulitis occurred in four patients only . CONCLUSION: Skin and soft tissue infections are continuing causes of morbidity in HIV-infected patients, even in the highly active antiretroviral therapy era. Br J Haematol, 2002 May, 117(2), 444 - 50 Early and late invasive pneumococcal infection following stem cell transplantation: a European Bone Marrow Transplantation survey; Engelhard D et al.; Streptococcus pneumoniae (S . pneumoniae) may cause severe and lethal infections months and years following stem cell transplantation (SCT) . In a prospective survey over a 3.5-year period, we assessed the incidence, risk factors and outcome for invasive pneumococcal infection (IPI) following SCT . Fifty-one episodes of IPI were reported: 43 episodes after bone marrow transplantation (BMT) and 8 after peripheral blood stem cell transplantation (PBSCT); 35 after allogeneic SCT and 16 after autologous SCT . Seven IPI episodes, all bacteraemias, were defined as early, occurring 1-35 d (median 3 d) post transplantation . Forty-four episodes were defined as late (> or = 100 d post SCT), occurring 4 months to 10 years (median 17 months) post transplantation . The incidences of early and late IPI were 2.03/1000 and 8.63/1000 transplantations respectively (P = 0.001) . A higher incidence of late IPI was observed after BMT than after PBSCT (10.99 versus 3.23/1000; P < 0.01) and after allogeneic versus autologous SCT (12.20 versus 4.60/1000; P < 0.01) . There was a higher estimated incidence of IPI in allogeneic patients with than in those without graft-versus-host disease (GVHD) (18.85 versus 8.25/1000; P = 0.015) . The mortality rate was 20%, including 2/7 of early and 8/44 of late IPI . S . pneumoniae is a rare but important complication during the aplastic phase after SCT . In conclusion, S . pneumoniae is a significant cause of morbidity late post-transplantation, especially in allogeneic patients, and particularly those with GVHD . The high IPI mortality rate, both early and late post-transplantation, requires preventive approaches, mainly effective immunization. Emerg Infect Dis, 2002 Apr, 8(4), 347 - 54 Antimicrobial use and antimicrobial resistance: a population perspective; Lipsitch M et al.; The need to stem the growing problem of antimicrobial resistance has prompted multiple, sometimes conflicting, calls for changes in the use of antimicrobial agents . One source of disagreement concerns the major mechanisms by which antibiotics select resistant strains . For infections like tuberculosis, in which resistance can emerge in treated hosts through mutation, prevention of antimicrobial resistance in individual hosts is a primary method of preventing the spread of resistant organisms in the community . By contrast, for many other important resistant pathogens, such as penicillin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus faecium resistance is mediated by the acquisition of genes or gene fragments by horizontal transfer; resistance in the treated host is a relatively rare event . For these organisms, indirect, population-level mechanisms of selection account for the increase in the prevalence of resistance . These mechanisms can operate even when treatment has a modest, or even negative, effect on an individual host's colonization with resistant organisms. J Immunol, 2002 May 1, 168(9), 4585 - 92 Identification of the streptococcal M protein binding site on membrane cofactor protein (CD46); Giannakis E et al.; Adherence of group A streptococcus (GAS) to keratinocytes is mediated by an interaction between human CD46 (membrane cofactor protein) with streptococcal cell surface M protein . CD46 belongs to a family of proteins that contain structurally related short consensus repeat (SCR) domains and regulate the activation of the complement components C3b and/or C4b . CD46 possesses four SCR domains and the aim of this study was to characterize their interaction with M protein . Following confirmation of the M6 protein-dependent interaction between GAS and human keratinocytes, we demonstrated that M6 protein binds soluble recombinant CD46 protein and to a CD46 construct containing only SCRs 3 and 4 . M6 protein did not bind to soluble recombinant CD46 chimeric proteins that had the third and/or fourth SCR domains replaced with the corresponding domains from another complement regulator, CD55 (decay-accelerating factor) . Homology-based molecular modeling of CD46 SCRs 3 and 4 revealed a cluster of positively charged residues between the interface of these SCR domains similar to the verified M protein binding sites on the plasma complement regulators factor H and C4b-binding protein . The presence of excess M6 protein did not inhibit the cofactor activity of CD46 and the presence of excess C3b did not inhibit the ability of CD46 to bind M6 protein by ELISA . In conclusion, 1) adherence of M6 GAS to keratinocytes is M protein dependent and 2) a major M protein binding site is located within SCRs 3 and 4, probably at the interface of these two domains, at a site distinct from the C3b-binding and cofactor site of CD46. Anal Biochem, 2002 May 1, 304(1), 110 - 6 PolC-type polymerase III of Streptococcus pyogenes and its use in screening for chemical inhibitors; Yang F et al.; The polC gene from Streptococcus pyogenes (S . pyogenes, strain SF370) has been cloned and expressed in Escherichia coli (E . coli) as a fusion protein containing an N-terminal histidine tag . The purified recombinant enzyme showed an apparent molecular mass of 160 kDa on SDS-PAGE and a specific activity of 3.5 nmol/min/mg when assayed in the presence of calf thymus DNA and the four deoxyribonucleoside triphosphates . This activity was inhibited by TMAU, a specific inhibitor of PolC . To facilitate kinetic studies, and high-throughput assays, a double-stranded oligo DNA primer/template was used as a substrate . The minimum requirement for the length of the substrate was a 20-base oligo primer annealed to a 35-base template . PolC activity was detected either by a filter-binding format or by a novel homogeneous scintillation proximity assay (SPA) . Sensitivity to inhibition by anilinouracil analogs was improved by incorporating three deoxycytidines in the template strand as the first 3 bases to be copied by the polymerase . Inhibition of PolC activity by trimethyleneanilinouracil by the filtration and SPA methods gave comparable results, but the SPA assay uses less radioactive label, is less time-consuming, and is amenable to high-throughput formatting . (c)2002 Elsevier Science (USA). Trop Anim Health Prod, 2002 Mar, 34(2), 95 - 104 Detection of subclinical mastitis in dromedary camels (Camelus dromedarius) using somatic cell counts and the N-acetyl-beta-D-glucosaminidase test; Guliye AY et al.; Somatic cell counts, N-acetyl-beta-D-glucosaminidase (NAGase) activity and the infection status of the udder were determined in quarter milk samples (n = 86) from 22 multiparous, clinically healthy camels, traditionally managed by Bedouin nomads in the Negev desert, Israel . Seventy (81.4%) of the 86 samples examined contained bacteria, of which 35 (40.7%) gave mixed isolations of two or more bacteria, suggesting the existence of subclinical mastitis in the camel herds studied . Sixteen samples (18.6%) yielded no growth of bacteria . Staphylococcus aureus, Micrococcus spp., Bacillus spp., Streptococcus dysgalactiae and Escherichia coli were the main organisms isolated . The somatic cell count (SCC) ranged from 1.01 x 105 to 11.78 x 106 cells/ml . NAGase values were between 41.4 and 372 NAGase units . Quarter milk samples that contained bacteria had significantly (p < 0.01) higher mean values for SCC but the mean NAGase levels were not significantly different for the bacteriologically negative and positive samples . There was a low correlation coefficient (r2 = 0.097) between the SCC and NAGase in the quarter milk samples from which bacteria were not isolated (n = 16) and a low negative correlation (r2 = -0.038) with the samples that contained bacteria (n = 70) . The type of bacteria had a significant effect (p < 0.01) on the SCC but not on the NAGase activity . Quarter samples from which Staphylococcus aureus (coagulase positive) was isolated showed the highest mean SCC and this organism is therefore suspected to be the underlying cause of the subclinical mastitis . The SCC gave a better indication of the presence of pathogenic microorganisms in milk samples than did NAGase. Am J Obstet Gynecol, 2002 Apr, 186(4), 618 - 26 Prevention of neonatal group B streptococcal disease: A combined intrapartum and neonatal protocol; Wendel GD Jr et al.; OBJECTIVE: We sought to assess the efficacy of a clinical protocol to reduce the incidence of early-onset neonatal group B Streptococcus (GBS) infection . STUDY DESIGN: We assessed neonatal sepsis from GBS and other organisms with use of a before-after study design to evaluate the effects of implementation of combined intrapartum antimicrobial prophylaxis given selectively to mothers with GBS risks and penicillin G given to all neonates . RESULTS: In 1994, early-onset GBS infection developed in 31 of 13,887 live births (2.2/1000), 13 preterm and 18 term cases . After implementation of the prophylaxis protocol (1995), 6 of 13,527 live births had early-onset GBS (0.4/1000) (P <.001) . There were no preterm (P =.0004) and 6 term GBS cases (P =.02) . The efficacy continued through 1999 (0.5/1000) without an increase in neonatal infections from other bacteria . CONCLUSION: Combined maternal and infant antimicrobial prophylaxis can significantly and safely reduce rates of early-onset GBS infection in both preterm and term infants. Curr Opin Infect Dis, 2002 Apr, 15(2), 163 - 7 Update on community-acquired pneumonia: impact of antibiotic resistance on clinical outcomes; Metlay JP; In contrast to the rapid expansion in the number of published studies reporting the increasing rate of antimicrobial drug resistance among common respiratory pathogens, there remain few controlled studies examining the impact of these trends on clinical outcomes . Those studies that are published are hampered by small sample sizes, biases inherent in observational designs, and the relative infrequency of isolates showing high-level resistance, particularly high-level beta-lactam resistance among clinical isolates of Streptococcus pneumoniae . This update summarizes recent published studies addressing the impact of drug resistance on outcomes for lower respiratory tract infections . The majority of these studies are retrospective cohort studies, focusing on the impact of beta-lactam-resistant pneumococcal infections in patients with community-acquired pneumonia . These studies support the conclusion that current levels of pneumococcal drug resistance do not result in clinical treatment failures for patients with community-acquired pneumonia . However, as patterns of drug resistance evolve, future studies will be needed to address the continued appropriateness of current empirical treatment guidelines for these patients. Curr Opin Infect Dis, 2001 Jun, 14(3), 337 - 42 Current approaches to otitis media; Cohen R et al.; Acute otitis media is the most commonly diagnosed illness in children, and is one of the most common reasons for antibiotic prescription . In many countries, antibiotic resistance is increasing among the bacteria that are implicated in acute otitis media, particularly Streptococcus pneumoniae . This evolution should stimulate changes in the management of acute otitis media, particularly the following: improvement in diagnostic accuracy; reduction in antibiotic use; selection of the most appropriate drugs at the appropriate dosage; reduction in duration of treatment, when possible; and implementation of new vaccines. Curr Opin Infect Dis, 2000 Apr, 13(2), 165 - 170 Update on acute otitis media; Balter SE et al.; The increase in drug-resistant Streptococcus pneumoniae has led to concerns about antibiotic resistance . Otitis media is the leading indication for antibiotic use in the United States . Evidence suggests that antibiotics do provide benefit to children with documented acute otitis media, and that carefully selected children may respond to shorter courses of antibiotics . Despite the increase in resistance, amoxicillin remains the drug of choice for acute otitis media even in areas with high levels of resistance . Pneumococcal conjugate vaccine and live attenuated influenza vaccine, which may be licensed in the future, will both have an impact on acute otitis media . During the next few years, these vaccines, along with more stringent diagnostic criteria, and more judicious use of antibiotics, may all contribute towards reducing the incidence of acute otitis media, the number of antibiotic prescriptions given and the adverse impact of antimicrobial resistance. Clin Orthop, 2002 May, (398), 182 - 8 Septic arthritis in postoperative anterior cruciate ligament reconstruction; Indelli PF et al.; A review of postoperative infected anterior cruciate ligament reconstructions was done on 3500 consecutive arthroscopic procedures . The purpose was to assess incidence, diagnosis, treatment, and outcome factors . Six postoperative intraarticular infections were detected . Average followup was 3 years (range, 2-8 years) . The rate of infection was 0.14% . Five men and one woman with a median age of 32.5 years (range, 20-51 years) comprised the study group . The average interval from the onset of symptoms to the initial arthroscopic intervention was 7.5 days (range, 2-20 days) . Staphylococcus aureus was present in three knees, Staphylococcus epidermidis in two, and Streptococcus nonhemolytic in one . All patients had initial arthroscopic debridement and lavage followed by 6 weeks of intravenous antibiotics . Two grafts were removed: one patient had delayed ligament reconstruction and the other had total knee arthroplasty . The remaining patients had full range of motion . In the group with the best result, two patients had Staphylococcus epidermidis and one had Staphylococcus aureus, which was treated 2 days after clinical symptoms began . The other two patients infected with Staphylococcus aureus had unsatisfactory results . Anterior cruciate ligament infection is rare, but diagnosable . When treated early with appropriate antibiotic therapy and arthroscopic debridement, four of six grafts were retained . If the infection does not respond rapidly to early therapy, then graft removal is an option. Biochem J, 2002 May 1, 363(Pt 3), 825 - 31 Characterization of Streptococcus pneumoniae thymidylate kinase: steady-state kinetics of the forward reaction and isothermal titration calorimetry; Petit CM et al.; Thymidylate kinase (TMK) catalyses the phosphorylation of dTMP to form dTDP in both the de novo and salvage pathways of dTTP synthesis . The tmk gene from the bacterial pathogen Streptococcus pneumoniae was identified . The gene, encoding a 212-amino-acid polypeptide (23352 Da), was cloned and overexpressed in Escherichia coli with an N-terminal hexahistidine tag . The enzyme was purified to homogeneity, and characterized in the forward reaction . The pH profile of TMK indicates that its activity is optimal at pH 8.5 . The substrate specificity of the enzyme was examined; it was found that not only ATP, but also dATP and to a lesser extent CTP, could act as phosphate donors, and dTMP and dUMP could serve as phosphate acceptors . Furthermore, AZT-MP (3'-azido-3'-deoxythymidine 5'-monophosphate) was shown not to be a substrate for S . pneumoniae TMK . Steady-state kinetics and inhibition studies with adenosine 5'-{beta-thio}diphosphate and dTDP in addition to isothermal titration calorimetry were performed . The data showed that binding follows an ordered pathway, in which ATP binds first with a K(m) of 235 +/- 46 microM and a K(d) of 116 +/- 3 microM, and dTMP binds secondly with a K(m) of 66 +/- 12 microM and a K(d) of 53 +/- 2 microM. Biotechniques, 2002 Apr, 32(4), 916, 918, 920, 922 - 3 Application of immuno-mass spectrometry to analysis of a bacterial virulence factor; Saouda M et al.; Here we describe a novel antibody-based assay that combines specificity of antibody with precision of mass spectral analysis . The assay is carried out in three steps using a single antigen capture and transfer reagent . The first step of the assay involves antibody immobilization . The second step is antigen capture and washing to remove unbound proteins . The third step involves the analysis of the captured antigens by surface enhanced laser desorption ionization time-of-flight mass spectrometry . The assay is facilitated by the ability of a single nonviable bacterial preparation expressing immunoglobulin-binding proteins that enable antibody immobilization, specific capture of fluid-phase antigen, and direct sample transfer to a protein chip for mass spectral analysis . Proof-of-concept studies using a model Streptococcus pyogenes virulence factor, the secreted cysteine protease SpeB, are presented. Rev Med Chil, 2002 Jan, 130(1), 26 - 34 {Resistance to Streptococcus pneumoniae to penicillin and its association with clinical and epidemiological factors}; Contreras L et al.; BACKGROUND: Penicillin and third generation cephalosporin resistant pneumococcal isolates have emerged in Chile, mainly in the pediatric population . These isolates complicate therapeutic alternatives, specially among patients with central nervous system infections . AIM: To assess the frequency of penicillin and third generation cephalosporin resistance among isolates obtained from pediatric patients with invasive pneumococcal infections, and to study serotypes and clinical risk factors associated with resistance . MATERIAL AND METHODS: Microbiological isolates obtained from children between April 1994 and May 1999 with pneumococcal invasive infections, were serotyped and analyzed according to their susceptibility to penicillin and cefotaxime by E-test and broth microdilution testing . Potential risk factors studied included patient's age, previous antibiotic use or admissions, comorbidity, and serotypes . RESULTS: Seventy eight patients were studied . Penicillin-resistant pneumococcal isolates were detected in 35.9% of cases (21.8% with intermediate and 14.1% with high level resistance) without significant variation among different clinical conditions . Most of the high level penicillin-resistant pneumoccocal isolates had MIC > or = 4 micrograms/mL (8 out of 11 strains) . One third of penicillin-resistant isolates also expressed cefotaxime resistance . Multivariate analysis indicated an age < or = 36 months (OR = 6.8; IC 95%: 1.4 to 33.5) and serotype 14 (OR = 6.3; IC 95%: 1.7 to 23.3) as factors associated with penicillin resistance . CONCLUSIONS: One third of the invasive pneumococcal isolates obtained from pediatric patients were resistant to penicillin . Risk factors involved a younger age and pneumococcal isolates belonging to serotype 14. J Biol Chem, 2002 Jul 12, 277(28), 24863 - 9 Epub 2002 Apr 17. Effect of the Streptococcus pneumoniae MmsA protein on the RecA protein-promoted three-strand exchange reaction . Implications for the mechanism of transformational recombination; Hedayati MA et al.; Streptococcus pneumoniae is a naturally transformable bacterium that is able to incorporate DNA from its environment into its own chromosome . This process, known as transformational recombination, is dependent in part on the mmsA gene, which encodes a protein having a sequence that is 40% identical to that of the Escherichia coli RecG protein, a junction-specific DNA helicase believed to be involved in the branch migration of recombinational intermediates . We have developed an expression system for the MmsA protein and have purified the MmsA protein to more than 99% homogeneity . The MmsA protein has DNA-dependent ATP hydrolysis and DNA junction-helicase activities that are similar to those of the E . coli RecG protein . The effect of the MmsA protein on the S . pneumoniae RecA protein-promoted three-strand exchange reaction was also investigated . In the standard direction (circular single-stranded (ss) DNA + linear double-stranded (ds) DNA --> linear ssDNA + nicked circular dsDNA), the MmsA protein appears to promote the branch migration of partially exchanged intermediates in a direction opposite of the RecA protein, resulting in a nearly complete inhibition of the overall strand exchange reaction . In the reverse direction (linear ssDNA + nicked circular dsDNA --> circular ssDNA + linear dsDNA), however, the MmsA protein appears to facilitate the conversion of partially exchanged intermediates into fully exchanged products, leading to a pronounced stimulation of the overall reaction . These results are discussed in terms of the molecular mechanism of transformational recombination. Biochim Biophys Acta, 2002 Feb 15, 1570(1), 75 - 9 Cloning and nucleotide sequence analysis of the Streptococcus sobrinus gtfU gene that produces a highly branched water-soluble glucan; Hanada N et al.; Streptococcus sobrinus has four gtf genes, gtfI, gtfS, gtfT, and gtfU, on the chromosome . These genes correspond respectively to the enzymes GTF-I, GTF-S1, GTF-S2, and GTF-S3 . An Escherichia coli MD66 clone that contained the S . sobrinus gtfU gene was characterized . Immunological properties showed that the protein produced by the E . coli MD66 clone was similar to S . sobrinus GTF-S1 . Biological properties and a linkage analysis of the glucans by 13C NMR spectrometry revealed that the protein produced by the E . coli MD66 clone was GTF-S1. Antimicrob Agents Chemother, 2002 May, 46(5), 1574 - 6 Macrolide and tetracycline resistance and molecular relationships of clinical strains of Streptococcus agalactiae; Culebras E et al.; Mechanisms for tetracycline and macrolide resistance in 54 isolates of erythromycin-resistant Streptococcus agalactiae were analyzed by PCR . The erm(B), erm(A), and mef(A) genes, either alone or in combination, were detected in all the erythromycin-resistant isolates . The tet(M) and tet(O) genes were responsible for tetracycline resistance . Random amplification of polymorphic DNA indicated different clonal origins of the isolates. Antimicrob Agents Chemother, 2002 May, 46(5), 1571 - 3 rpoB mutation conferring rifampin resistance in Streptococcus pyogenes; Aubry-Damon H et al.; Streptococcus pyogenes BM4478 and Staphylococcus aureus BM4479 were isolated from a patient undergoing rifampin therapy . High-level resistance to rifampin was due to the following mutations in the rpoB gene: Ser522Leu in strain BM4478 and His526Asn and Ser574Leu in strain BM4479. Antimicrob Agents Chemother, 2002 May, 46(5), 1425 - 34 Pharmacodynamic assessment of clarithromycin in a murine model of pneumococcal pneumonia; Tessier PR et al.; The pharmacodynamic profile of clarithromycin (CLR) was evaluated with a murine model of pneumonia . Eight Streptococcus pneumoniae isolates, including three macrolide-sensitive and five macrolide-resistant strains, were inoculated intratracheally into immunocompromised ICR mice as 10(8)-CFU bacterial suspensions . Orally administered CLR daily doses ranging from 5 to 600 mg/kg of body weight were given over 5 days, during which animal survival was monitored . The bacterial density in lung tissues was examined after 24 h of CLR treatment and in control groups . Pharmacokinetic analysis of CLR in mice demonstrated that the regimen of 150 mg/kg twice a day was representative of human pharmacokinetics and was used to compare the efficacy of CLR against sensitive and resistant S . pneumoniae strains . Immunocompetent CBA/J mice were also infected and treated as described above and evaluated for bacterial density and survival to assess the effect of the presence of leukocytes . All three pharmacodynamic parameters, the duration (percent) of the time that serum CLR concentrations remain above the MIC (%T>MIC), the ratio of the area under the concentration-time curve from 0 to 24 h (AUC(0-24)) to the MIC, and the ratio of the maximum concentration of drug in serum to the MIC, were found to be closely correlated to CLR bacterial efficacy (P < 0.001) . Furthermore, all parameters had close correlation to bacterial density (r(2) = 0.72 to 0.82), median survival (r(2) = 0.93 to 0.94), and total percent survival (r(2) = 0.91 to 0.92) . These in vivo data suggest that the bacterial activity of CLR is closely correlated with all three parameters over a wide range of exposures and, as a consequence of parameter interdependency, AUC(0-24)/MIC is the most reasonable predictor of antibiotic efficacy . In this neutropenic pneumonia model, CLR was less efficacious against S . pneumoniae strains for which MICs were >or=4 microg/ml . However, the presence of leukocytes in the immunocompetent mice resulted in improved bactericidal activity, relative to that in the neutropenic animals, despite an MIC of 4 microg/ml. Antimicrob Agents Chemother, 2002 May, 46(5), 1345 - 51 Pharmacodynamic activity and efficacy of linezolid in a rat model of pneumococcal pneumonia; Gentry-Nielsen MJ et al.; Linezolid is a new oxazolidinone antibiotic with potent activity against gram-positive bacteria, including Streptococcus pneumoniae . The pharmacodynamic activity and in vivo efficacy of linezolid were compared to those of ceftriaxone in an immunocompetent rat model of pneumococcal pneumonia . Rats infected intratracheally with 8 x 10(7) CFU of a penicillin-sensitive (MIC, 0.032 microg/ml) strain of S . pneumoniae were treated for 5 days beginning 18 h postinfection . Groups of rats were sham treated with oral phosphate-buffered saline or received oral liquid linezolid at 25 or 50 mg/kg of body weight twice a day (b.i.d.) or subcutaneous ceftriaxone at 100 mg/kg once daily . Mortality was monitored for 10 days postinfection; blood culturing was performed on day 1 (pretreatment) and on days 3, 5, and 10 postinfection for the determination of bacteremia . Serum also was collected for the determination of pharmacokinetic and pharmacodynamic parameters at 30 min and at 3, 5, and 12 h (linezolid) or 3, 5, and 24 h (ceftriaxone) postdose . The cumulative mortality rates were 100% for the sham-treated group, 58.3% for the low-dose linezolid group, 8.3% for the high-dose linezolid group, and 0% for the ceftriaxone group . Rats in each of the antibiotic treatment groups had significantly fewer bacteria (P < 0.00001) in their bronchoalveolar lavage fluid (BALF) on day 3 postinfection than sham-treated rats . There also were significantly fewer organisms in the BALF of rats treated with ceftriaxone than in the BALF of rats treated with either dose of linezolid . Oral linezolid at 50 mg/kg b.i.d . therefore was as effective as ceftriaxone in experimental pneumococcal pneumonia, whereas the 25-mg/kg b.i.d . dose was significantly less effective . All pharmacodynamic parameters reflected efficacy and were significantly different for the two dosage regimens of linezolid (P < 0.01) . However, the free-fraction pharmacodynamic parameters predictive of outcome were a value of >39% for the percentage of time in the experimental dosing interval during which the linezolid concentration exceeded the MIC and a value of >147 for the ratio of the area under the serum concentration-time curve to the MIC. Antimicrob Agents Chemother, 2002 May, 46(5), 1340 - 4 Effects of specific antibodies against Streptococcus pneumoniae on pharmacodynamic parameters of beta-lactams in a mouse sepsis model; Casal J et al.; A dose-ranging study to investigate the in vivo effects of the presence of specific antibodies on the efficacy of beta-lactam treatment of sepsis caused by Streptococcus pneumoniae (non-beta-lactam-susceptible serotype 6B isolate) was performed with a BALB/c mouse model . Hyperimmune serum was obtained from mice immunized with the heat-inactivated strain . The rate of mortality was 100% in nontreated animals in the absence of specific antibodies . A single injection of a one-half or one-quarter dilution of hyperimmune serum produced 60 to 40% survival rates . In the absence of specific antibodies, the minimal effective doses of amoxicillin and cefotaxime that produced survival rates of 100 and 80% were 25 and 50 mg/kg of body weight (three times a day for up to six doses), respectively . These doses produced times that the levels in serum remained above the MIC (deltaT > MICs) approximately 30% of the dosing interval . When specific antibodies were present (by administration of a one-half or one-quarter dilution of hyperimmune serum), the minimal effective doses of the antibiotics were 3.12 and 6.25 mg/kg ( approximately 8 times lower), with the deltaT > MICs being approximately 3 and 5% of the dosing interval for amoxicillin and cefotaxime, respectively . This in vivo combined pharmacodynamic effect offers possibilities that can be used to address penicillin resistance. Antimicrob Agents Chemother, 2002 May, 46(5), 1302 - 9 Effects of compounds found in propolis on Streptococcus mutans growth and on glucosyltransferase activity; Koo H et al.; Propolis, a resinous bee product, has been shown to inhibit the growth of oral microorganisms and the activity of bacterium-derived glucosyltransferases (GTFs) . Several compounds, mainly polyphenolics, have been identified in this natural product . The present study evaluated the effects of distinct chemical groups found in propolis on the activity of GTF enzymes in solution and on the surface of saliva-coated hydroxyapatite (sHA) beads . Thirty compounds, including flavonoids, cinnamic acid derivatives, and terpenoids, were tested for the ability to inhibit GTFs B, C, and D from Streptococcus mutans and GTF from S . sanguinis (GTF Ss) . Flavones and flavonols were potent inhibitors of GTF activity in solution; lesser effects were noted on insolubilized enzymes . Apigenin, a 4',5,7-trihydroxyflavone, was the most effective inhibitor of GTFs, both in solution (90.5 to 95% inhibition at a concentration of 135 microg/ml) and on the surface of sHA beads (30 to 60% at 135 microg/ml) . Antibacterial activity was determined by using MICs, minimum bactericidal concentrations (MBCs), and time-kill studies . Flavanones and some dihydroflavonols, as well as the sesquiterpene tt-farnesol, inhibited the growth of S . mutans and S . sobrinus; tt-farnesol was the most effective antibacterial compound (MICs of 14 to 28 microg/ml and MBCs of 56 to 112 microg/ml) . tt-Farnesol (56 to 112 microg/ml) produced a 3-log-fold reduction in the bacterial population after 4 h of incubation . Cinnamic acid derivatives had negligible biological activities . Several of the compounds identified in propolis inhibit GTF activities and bacterial growth . Apigenin is a novel and potent inhibitor of GTF activity, and tt-farnesol was found to be an effective antibacterial agent. Antimicrob Agents Chemother, 2002 May, 46(5), 1295 - 301 Antimicrobial resistance among clinical isolates of Streptococcus pneumoniae in Canada during 2000; Low DE et al.; A total of 2,245 clinical isolates of Streptococcus pneumoniae were collected from 63 microbiology laboratories from across Canada during 2000 and characterized at a central laboratory . Of these isolates, 12.4% were not susceptible to penicillin (penicillin MIC, >or=0.12 microg/ml) and 5.8% were resistant (MIC, >or=2 microg/ml) . Resistance rates among non-beta-lactam agents were the following: macrolides, 11.1%; clindamycin, 5.7%; chloramphenicol, 2.2%; levofloxacin, 0.9%; gatifloxacin, 0.8%; moxifloxacin, 0.4%; and trimethoprim-sulfamethoxazole, 11.3% . The MICs at which 90% of the isolates were inhibited (MIC90s) of the fluoroquinolones were the following: gemifloxacin, 0.03 microg/ml; BMS-284756, 0.06 microg/ml; moxifloxacin, 0.12 microg/ml; gatifloxacin, 0.25 microg/ml; levofloxacin, 1 microg/ml; and ciprofloxacin, 1 microg/ml . Of 578 isolates from the lower respiratory tract, 21 (3.6%) were inhibited at ciprofloxacin MICs of >or=4 microg/ml . None of the 768 isolates from children were inhibited at ciprofloxacin MICs of >or=4 microg/ml, compared to 3 of 731 (0.6%) from those ages 15 to 64 (all of these >60 years old), and 27 of 707 (3.8%) from those over 65 . The MIC90s for ABT-773 and telithromycin were 0.015 microg/ml for macrolide-susceptible isolates and 0.12 and 0.5 microg/ml, respectively, for macrolide-resistant isolates . The MIC of linezolid was <or=2 microg/ml for all isolates . Many of the new antimicrobial agents tested in this study appear to have potential for the treatment of multidrug-resistant strains of pneumococci. Antimicrob Agents Chemother, 2002 May, 46(5), 1199 - 203 Emergence of group A streptococcus strains with different mechanisms of macrolide resistance; Bingen E et al.; The mechanisms of resistance to macrolides in seven group A streptococcal (Streptococcus pyogenes) isolates that were the cause of pharyngitis in children who were unsuccessfully treated with azithromycin (10 mg/kg of body weight/day for 3 days) were evaluated . All posttreatment strains were found to be genetically related to the pretreatment isolates by random amplified polymorphism DNA analysis and pulsed-field gel electrophoresis . Two isolates had acquired either a mef(A) or an erm(B) gene, responsible for macrolide efflux and ribosomal modification, respectively . Three isolates displayed mutations in the gene encoding the L4 ribosomal protein that is part of the exit tunnel within the 50S subunit of the bacterial ribosome . In the two remaining posttreatment strains, the mechanisms of macrolide resistance could not be elucidated. FEMS Microbiol Lett, 2002 Mar 5, 208(2), 175 - 8 Oral colonization and immune responses to Streptococcus gordonii expressing a pertussis toxin S1 fragment in mice; Lee SF et al.; The ability of a recombinant Streptococcus gordonii RJM4 expressing the N-terminal 179-amino acid fragment of S1 subunit of pertussis toxin (PT) as a SpaP/S1 fusion protein was tested for oral colonization and immunogenicity in BALB/c mice . Following two consecutive oral inoculations, 100% of the mice were colonized by the recombinant strains for up to 9 weeks and >60% of the animals still retained the strains after 19 weeks . RJM4 recovered from the animals continued to express the SpaP/S1 fusion protein indicating the stability of the fusion gene in vivo . Secretory (S) IgA antibody against PT could be detected in saliva from RJM4-colonized mice but not from the control groups of mice . SIgA against SpaP was also detected in saliva from the RJM4-inoculated and the S . gordonii SL3 (control)-inoculated mice . Serum antibodies against PT and SpaP were not detected in these animals . In conclusion, long-term oral colonization of BALB/c mice with our recombinant S . gordonii was established and the colonization elicited mucosal antibodies against PT and SpaP. Neurol Res, 2002 Apr, 24(3), 307 - 10 Experimental bacterial meningitis in rats: demonstration of hydrocephalus and meningeal enhancement by magnetic resonance imaging; Wiesmann M et al.; We investigated whether magnetic resonance imaging (MRI) is able to detect intracranial manifestations of advanced bacterial meningitis in rats . Meningitis was induced in nine animals by injecting 150 microl 10(7) colony forming units per ml of Streptococcus pneumoniae into the cisterna magna . MRI was performed 24 h (n = 5) and 48 h (n = 4) after infection . Controls included (I) animals that were injected intracisternally with 150 microl phosphate-buffered saline or (II) animals without puncture of the cisterna magna . T2-weighted and T1-weighted MR images before and after administration of 0.3 mmol kg(-1) of gadolinium-DTPA were obtained . Hydrocephalus was found in 7 of 9 infected animals, but not in the control group . Abnormal leptomeningeal enhancement was found in all infected animals, but in none of the controls . The animals imaged after 48 h showed a more pronounced hydrocephalus and a more intense leptomeningeal enhancement than animals imaged after 24 h . Even in small animals such as rats, MRI can be used to detect the presence of bacterial meningitis and its associated complications . MRI may be a useful noninvasive method for monitoring the possible effect of adjunctive therapeutic strategies in experimental studies of meningitis. J Infect Chemother, 2002 Mar, 8(1), 28 - 32 High frequency of erythromycin A resistance and distribution of mefE and ermB genes in clinical isolates of Streptococcus pneumoniae in Japan; Okamoto H et al.; The ermB and mefE genes are important in terms of their responsibility for macrolide resistance in Streptococcus pneumoniae . We investigated the distribution of the ermB and mefE genes in erythromycin A-resistant S . pneumoniae isolated in our hospital during the period 1995-1998 . All amoxicillin-low-susceptible isolates were considered to be resistant to erythromycin A . All isolates with resistance to erythromycin A (minimum inhibitory concentrations {MICs}, > or =0.5 microg/ml) possessed ermB or mefE genes . The MICs of erythromycin A for most mefE-positive isolates ranged from 0.5 to 2 microg/ml . On the other hand, approximately 85% of ermB-positive isolates demonstrated high-level resistance to erythromycin A (MICs, > or =4 microg/ml) while the others showed low-level resistance (MICs, 0.5 to 2 microg/ml) . In ermB-positive isolates with low-level resistance, high-level resistant mutants were selected with a frequency of 3.1 x 10(-6)-1.8 x 10(-3) on agar containing 4-32 MIC of erythromycin A, whereas in mefE-positive isolates, no high-level resistant mutants were detected . Mutants from ermB-positive isolates with low-level resistance showed reversibility and heterogeneity . Our data indicated a wide distribution of erythromycin A-resistant isolates with mefE or ermB genes among amoxicillin-low-susceptible S . pneumoniae in Japan . In addition, it is likely that ermB-positive isolates with low-level resistance show heterogeneous high-level resistance. Eur J Clin Microbiol Infect Dis, 2002 Mar, 21(3), 181 - 8 Epub 2002 Mar 16. Prevalence, determinants, and molecular epidemiology of Streptococcus pneumoniae isolates colonizing the nasopharynx of healthy children in Rome; Petrosillo N et al.; The aim of this study was to determine the factors favouring Streptococcus pneumoniae nasopharyngeal colonization of healthy children attending daycare centres and to describe the circulation of penicillin-nonsusceptible strains using molecular techniques . A single nasopharyngeal swab was obtained from 610 children attending daycare centres in the southeast area of Rome . Streptococcus pneumoniae isolates were serotyped, and antibiotic susceptibility was assayed by the E test . The genetic determinants of erythromycin resistance were detected by a duplex polymerase chain reaction, and the penicillin-nonsusceptible isolates were typed by pulsed-field gel electrophoresis . The overall carriage rate of Streptococcus pneumoniae was 14.9% . Living with more than three persons in the same household was the only risk factor statistically associated with carriage . Sixteen of 85 (18.8%) strains were nonsusceptible to penicillin, and 44 (52%) were resistant to erythromycin . Of the erythromycin-resistant strains, the vast majority showed a high level of resistance and carried the erm(B) gene . The penicillin-nonsusceptible strains belonged to six different serotypes; molecular typing showed that in only one case (2 strains) was there a circulation of the same clone in the same daycare centre . In view of the high rate of resistant Streptococcus pneumoniae strains, risk factors for carriage of resistant strains were evaluated . Children who received macrolides in the previous month had a higher risk of being colonized by macrolide-resistant strains as well as by strains resistant to both penicillin and erythromycin . Limiting the use of antibiotics in children seems the most appropriate measure to control the spread of antibiotic-resistant strains. Int J Pediatr Otorhinolaryngol, 2002 Apr 25, 63(2), 149 - 54 Possible inflammatory mediators in tympanosclerosis development; Forseni Flodin M et al.; OBJECTIVE: Tympano/myringosclerosis is a sequelae following otitis media, causing hearing disability . There is no curative treatment for this condition . In order to illuminate the correlation of inflammatory mediators in otitis media and tympanosclerosis development, the present study was performed . METHODS: In an animal model, Streptococcus pneumonia bacteria were inoculated to the middle ear . Furthermore, biopsies were harvested during surgery, from children suffering from secretory otitis media and from patients with already established tympanosclerosis . The early inflammatory parameters were investigated in the rat model as well as in the patient material . The lymphocytic population, macrophages, interleukin-6, inducible nitric oxide synthase and MHC class II were studied by immunohistochemistry and by mRNA in situ hybridization . RESULTS: Myringosclerosis was produced in 30% of the rats studied . Macrophages were the first cells to invade the middle ear after induction of otitis media, followed by B-cells and T-cells . IL-6 m-RNA was found as early as 1 h after inoculation . Cells, expressing inducible nitric oxide synthase, seemed to be activated macrophages . Osteoclast like cells, positive in immunohistechemical macrophage staining, were found close to the insertion of the tympanic membrane . The human specimens showed a more immunological active stage in the secretory otitis media group as compared to the specimens with tympanosclerosis . CONCLUSIONS: The immunocompetent cells and some mediators are presented time dependently in otitis media and a possible reaction sequence, leading to differentiation of macrophages into osteoclasts is presented . This may lead to tympanosclerosis development. Zhonghua Kou Qiang Yi Xue Za Zhi, 2002 Jan, 37(1), 4 - 7 {DNA vaccine encoding Streptococcus mutans surface protein protected gnotobiotic rats from caries}; Fan M et al.; OBJECTIVE: Protein of Streptococcus mutans is considered as one of the virulence factors due to its ability to mediate the initial attachment of Streptococcus mutans to tooth surface . In this study, an anticaries DNA vaccine pCIA-P was used to immunize rats . The expression of PAc in different tissues in vivo, specific immune response and protection effects against dental caries were observed . METHODS: Plasmid pCIA-P was injected into rats by two different routs: intramuscular injection (i.m.) and targeted salivary gland immunization (TSG) . Immunohistochemistry technique was used to detect the expression of PAc . Gnotobiotic rats were vaccinated with pCIA-P by three different approaches: TSG, intramuscular injection and buccal mucosal injection (i.o.) . The specific immune responses were evaluated by ELISA and their anticaries effects were evaluated by Keyes caries scores . RESULTS: PAc was expressed in the sarcoplasm and sarcolemma of muscle fibers and submandibular glands, especially strongly positive in duct regions . The levels of serum specific anti-PAc IgG and salivary specific anti-PAc IgA in TSG immunization and buccal mucosal immunization group were significantly higher than those of other groups . The Keyes caries scores of those two groups were significantly lower than those of other groups . CONCLUSION: The plasmid pCIA-P could provoke specific immune responses as a novel immunogen . Mucosal immunization with pCIA-P appears to be an effective genetic immunization method against dental caries. Saudi Med J, 2002 Apr, 23(4), 400 - 4 Streptococcus pneumoniae resistance to penicillin and ceftriaxone in a tertiary care center in Saudi Arabia; Al-Aqeeli AA et al.; OBJECTIVE: The proportion of penicillin and ceftriaxone resistant Streptococcus pneumoniae isolates and associated risk factors varies by geographic areas in the world . We conducted a retrospective study to determine the extent of penicillin and ceftriaxone non-susceptible Streptococcus pneumoniae bacteremia in a tertiary care medical center in the city of Riyadh, Kingdom of Saudi Arabia . METHODS: We reviewed 172 episodes of Streptrococcus pneumoniae bacteremic diseases involving 160 hospitalized patients at King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia, over a 5 year period between January 1995 through to December 1999 . Patients' characteristics and underlying illnesses of those patients with bacteremias and meningitis caused by Streptococccus pneumoniae as well as antimicrobial susceptibility were examined . RESULTS: The majority of patients affected with Streptococcus pneumoniae bacteremia were children <5 years of age (number=91, 53%) . Malignant diseases were the main underlying diagnosis in our patient population affected with pneumoncoccal bacteremia (number=46, 27%) . Overall (51%) of the isolates were penicillin non-susceptible; of these (7%) were highly resistant . The overall resistance rate to ceftriaxone was 7% . CONCLUSION: With the high prevalence in Streptococcus pneumoniae antimicrobial resistance to penicillin and ceftriaxone, it is important to continue surveillance of infections caused by Streptococcus pneumoniae, and also we recommend that guidelines for treatment and prevention of pneumococcal infection must be addressed by health care and public health agencies. Infect Immun, 2002 May, 70(5), 2721 - 4 Passive immunization with bovine milk containing antibodies to a cell surface protein antigen-glucosyltransferase fusion protein protects rats against dental caries; Mitoma M et al.; Cell surface protein antigen (PAc) and glucosyltransferases (GTF) of Streptococcus mutans are major colonization factors of the organism . We prepared bovine milk containing antibodies against a fusion of the saliva-binding alanine-rich region of PAc with the glucan-binding domain of GTF-I . This study examined the effect of the immune milk on the cariogenicity of S . mutans in a rat model . Concentrated immune milk was fed to rats once a day for 55 days . The group that received immune milk had significantly less caries development than controls. Infect Immun, 2002 May, 70(5), 2526 - 34 Role of pneumococcal surface protein C in nasopharyngeal carriage and pneumonia and its ability to elicit protection against carriage of Streptococcus pneumoniae; Balachandran P et al.; Previous studies suggested that PspC is important in adherence and colonization within the nasopharynx . In this study, we conducted mutational studies to further identify the role PspC plays in the pathogenesis of pneumococci . pspC and/or pspA was insertionally inactivated in a serotype 2 Streptococcus pneumoniae strain and in a serotype 19 S . pneumoniae strain . In the mouse colonization model, pneumococcal strains with mutations in pspC were significantly attenuated in their abilities to colonize . In a mouse pneumonia model, strains with mutations in pspC were unable to infect or multiply within the lung . Using reverse transcriptase PCR we were able to demonstrate that pspC is actively transcribed in vivo, when the bacteria are growing in the nasal cavity and in the lungs . In the bacteremia model, a strain mutated for pspC alone behaved like the wild type, but the absence of both pspC and pspA caused accelerated clearance of the bacteria . Intranasal immunization with PspC with cholera toxin subunit B as an adjuvant protected against intranasal challenge . Evidence was also obtained that revertants that spontaneously acquired PspC expression could multiply and colonize the nasal tissue . This latter finding strongly indicates that pneumococci are actively metabolizing and growing while in the nasopharynx. Infect Immun, 2002 May, 70(5), 2487 - 91 Analysis of factors affecting surface expression and immunogenicity of recombinant proteins expressed by gram-positive commensal vectors; Bolken TC et al.; Several key protein structural attributes were altered in an effort to optimize expression and immunogenicity of a foreign protein (M protein from Streptococcus pyogenes) exposed on the surface of Streptococcus gordonii commensal bacterial vectors: (i) a shorter N-terminal region, (ii) the addition of a 94-amino-acid spacer, and (iii) the addition of extra C-repeat regions (CRR) from the M6 protein . A decrease in the amount of cell surface M6 was observed upon deletion of 10 or more amino acid residues at the N terminus . On the other hand, reactivity of monoclonal antibody to surface M6 increased with the addition of the spacer adjacent to the proline- and glycine-rich region, and an increase in epitope dosage was obtained by adding another CRR immediately downstream of the original CRR . The results obtained should facilitate the design of improved vaccine candidates using this antigen delivery technology. Infect Immun, 2002 May, 70(5), 2434 - 40 rgf encodes a novel two-component signal transduction system of Streptococcus agalactiae; Spellerberg B et al.; The adhesion of gram-positive bacteria to extracellular matrix (ECM) proteins is regarded as an important determinant of pathogenicity . A comparison of the adhesion of Streptococcus agalactiae strain O90R to different ECM proteins showed that the most pronounced binding could be observed for immobilized fibrinogen . To investigate the genetic determinants of S . agalactiae fibrinogen binding, a pGhost9:ISS1 mutant library was screened for mutants displaying reduced agglutination of fibrinogen-coated latex beads . A putative two-component signal transduction system was identified and designated rgfBDAC . It comprises genes encoding a putative response regulator of 218 amino acids and a putative histidine kinase of 426 amino acids . Comparison of the deduced proteins with the GenBank database revealed a significant similarity to quorum-sensing systems of gram-positive pathogens . Transcription analysis of the rgf locus showed that the encoding genes are located on one transcript . To further characterize the influence of the putative histidine kinase encoded in the rgf locus on the adhesion of S . agalactiae to immobilized fibrinogen, a targeted mutant of rgfC was generated . In comparison to the wild-type strain this mutant demonstrated altered fibrinogen binding capacities depending on bacterial cell density . Transcription analysis of secreted and surface-localized S . agalactiae proteins in the wild type and the rgfC mutant strain revealed that mRNA levels of the C5a peptidase gene scpB were increased in the mutant strain while the transcription of the secreted CAMP factor gene cfb was unaffected by this mutation . Based on these results, we hypothesize that rgf regulates the expression of bacterial cell surface components. Int J Infect Dis, 2001, 5(4), 199 - 201 Obstacles to penicillin use in treating pneumococcal infection; Nord JA et al.; OBJECTIVES: To determine the pattern of penicillin use in the treatment of pneumococcal pneumonia, and factors contributing to the use of alternative antibiotics . METHODS: This study included all adult inpatients of St . Vincent's Hospital and Medical Center who had documented pneumococcal pneumonia between December 1998 and October 1999 . St . Vincent's is a 600 bed tertiary teaching hospital in New York City . Patients who had Streptococcus pneumoniae isolated from a respiratory tract specimen were identified through microbiology laboratory records . A retrospective chart review of these patients was conducted, and those identified with clinical pneumonia were included in this study . Antibiotic use, patient demographics, resistance data, and clinician awareness of the antibiotic susceptibility results were noted . RESULTS: Sixty adult patients hospitalized with documented pneumococcal pneumonia were identified . Thirteen (21.6%) of the 60 patients received penicillin or ampicillin . Susceptibility results were not noted in the medical record in 21 (35.0%) of the 60 patients, and none received penicillin . High rates of reported penicillin allergy in 8 (13.3%) of the 60 patients, and reluctance to use penicillin when isolates demonstrated intermediate susceptibility in 8 (13.3%) of the 60 patients were observed . CONCLUSIONS: Several remediable obstacles to penicillin use were identified in this study . An increased awareness of susceptibility results by physicians and education of practitioners could have increased the use of penicillin as therapy to two-thirds of these patients. Mol Microbiol, 2002 Mar, 43(6), 1591 - 601 Two DNA-binding domains of Mga are required for virulence gene activation in the group A streptococcus; McIver KS et al.; Mga is a DNA-binding protein that activates expression of several important virulence genes in the group A streptococcus (GAS), including those encoding M protein (emm), C5a peptidase (scpA) and Mga (mga) . To determine the functionality of four potential helix-turn-helix DNA-binding motifs (HTH1-HTH4) identified within the amino-terminus of Mga, alanine substitutions were introduced within each domain in a MBP-Mga fusion allele and purified proteins were assayed for binding to Mga-specific promoter fragments (Pmga, PscpA and Pemm) in vitro . Although HTH-1 and HTH-2 mutations showed wild type DNA-binding activity, an altered HTH-3 domain resulted in reduced binding to the three promoters and an HTH-4 mutant was devoid of detectable binding activity . Plasmid-encoded expression of the HTH-3 and HTH-4 alleles from a constitutive promoter (Pspac) in the mga-deleted GAS strain JRS519 demonstrated that Mga-regulated emm expression correlated directly to the DNA-binding activity observed for each mutant protein in vitro . Single-copy expression of HTH-3 and HTH-4 from their native Pmga resulted in a dramatic reduction in autoregulated mga expression in both mutant strains . Thus, Mga appears to contain two DNA-binding domains (HTH-3 and HTH-4) that are required for direct activation of the Mga virulence regulon in vivo. J Microbiol Immunol Infect, 2002 Mar, 35(1), 23 - 8 Clinical outcome of invasive pneumococcal infection in children: a 10-year retrospective analysis; Ma JS et al.; A retrospective study was conducted on 72 children admitted to a medical center in Taiwan due to invasive pneumococcal infections diagnosed between January 1990 and April 2000 . Of these patients, 28 had meningitis and 44 had other invasive diseases . Forty-one (56.9%) strains of Streptococcus pneumoniae showed reduced susceptibility to penicillin by the oxacillin disc diffusion method . The total mortality was 20.8%, 32.1% for meningitis, and 13.6% for other invasive diseases . Ten (52.6%) of the patients survived from meningitis had long-term sequelae . Statistical analysis showed that initial presentation of coma, shock, respiratory distress requiring mechanical ventilation, and leukopenia (leukocyte <4,000 /mm3) were associated with mortality of invasive pneumococcal infections . Low cerebrospinal fluid leukocyte count (<50 /mm3) and high cerebrospinal fluid protein level (> or = 660 mg/dL) were also associated with mortality of meningitis . The presence of underlying diseases and high alanine aminotransferase level (> or = 100 U/L) were associated with fatal non-meningitic invasive diseases . Patients with shock and high alanine aminotransferase level but without high C-reactive protein level (> or = 20 mg/dL) were associated with rapidly fatal outcome . The outcome of invasive pneumococcal diseases was not associated with penicillin susceptibility. J Microbiol Immunol Infect, 2002 Mar, 35(1), 17 - 22 Streptococcus pneumoniae bacteremia in southern Taiwan; Lee CK et al.; Streptococcus pneumoniae bacteremia was diagnosed in 33 patients between June 1999 and November 2000 at the Chang Gung Memorial Hospital-Kaohsiung in southern Taiwan . Antimicrobial susceptibility and serotyping of the clinical isolates were performed . Pneumonia was diagnosed in 19 patients, primary bacteremia in 13, and meningitis in one . The most common serotypes were types 14, 3, and 23F . Fourteen (42.4%) isolates of S . pneumoniae were non-susceptible to penicillin . High antimicrobial resistance rates were found to erythromycin (81.9%), tetracycline (69.7%), clindamycin (69.7%), trimethoprim-sulfamethoxazole (33.1%), and chloramphenicol (12.1%) . The mortality was 42.4% and liver cirrhosis was an independent risk factor for mortality (odds ratio = 9.998; 95% confidence interval, 1.011-98.85; p=0.049) . All isolated strains were covered by 23-valent the pneumococcal vaccine . Given the increasing prevalence of penicillin non-susceptible S . pneumoniae infection in the community, ongoing periodic monitoring of the evolutionary clinical situation is needed . Results of this study suggest that patients with liver cirrhosis should be inoculated with pneumococcal vaccine. Lancet Infect Dis, 2002 Mar, 2(3), 156 - 62 Superantigens: microbial agents that corrupt immunity; Llewelyn M et al.; Microbial superantigens are a family of protein exotoxins that share the ability to trigger excessive and aberrant activation of T cells . The best characterised are the staphylococcal enterotoxins and the streptococcal pyrogenic exotoxins that trigger the staphylococcal and streptococcal toxic shock syndromes . It is now apparent that superantigens have a wider role in the pathology of infectious diseases than has previously been appreciated . Staphylococcus aureus and Streptococcus pyogenes together produce 19 different superantigens . The range of microorganisms known to produce superantigens has expanded to include Gram negative bacteria, mycoplasma, and viruses . Research is beginning to shed light on the more subtle parts these molecules play in causing disease and to produce some real possibilities for specific treatment of superantigen-induced toxicity . We aim to highlight these new developments and review the science behind these fascinating molecules. Int J Parasitol, 2002 May, 32(5), 575 - 80 Adapting immunity with subunit vaccines: case studies with group A Streptococcus and malaria; Good MF et al.; Although vaccines have widely been regarded as the most cost-effective way to improve public health, for some organisms new technological advances in vaccine design and delivery, incurring additional developmental costs, will be essential . These organisms are typically those for which natural immunity is either slow to develop or does not develop at all . Clearly, such organisms have evolved strategies to evade immune responses and innovative approaches will be required to induce a type of immune response which is both different to that which develops naturally and is effective . This article describes some approaches to develop vaccines for two such organisms (malaria parasites and Streptococcus pyogenes (group A Streptococcus)) that are associated with widespread mortality and morbidity, mostly in the poorest countries of the world . At this stage, the challenges are primarily scientific, but if these hurdles are surmounted then the challenges will become financial ones--developing much needed vaccines for people least able to afford them. J Clin Periodontol, 2002 Mar, 29(3), 260 - 8 Subgingival microbial profiles in refractory periodontal disease; Socransky SS et al.; BACKGROUND/AIM: The purpose of the present investigation was to examine subgingival microbial profiles associated with refractory periodontitis and to seek such profiles in periodontally healthy, periodontally well-maintained elder and untreated periodontitis subjects . METHODS: 36 subjects were defined as refractory on the basis of further attachment loss after scaling and root planing, surgery and systemically administered antibiotics . A total of 890 subgingival plaque samples (mean/subject=24.7) were taken from the mesial aspect of each tooth in each subject at baseline and individually processed for their content of 40 subgingival taxa using checkerboard DNA-DNA hybridization . Cluster analysis was performed on mean within subject species counts using the chord coefficient and an average unweighted linkage sort . Significant differences among clusters for individual and complexes of species were sought using the Kruskal Wallis test . The microbial profiles of the refractory subjects were compared with those of 27 periodontally healthy subjects (n plaque samples=708), 35 periodontally well-maintained elder subjects (n plaque samples=801) and 115 untreated adult periodontitis subjects (n plaque samples=2871) . RESULTS: 28 of 36 refractory subjects fell into 4 clusters with >29% similarity . 10 of 40 species and 4 of 7 complexes differed significantly among clusters . Profile (Cluster) I (n=4) was characterized by high proportions of "yellow" and "green" complex species, profile II (n=3) by low total counts and high proportions of "orange" and "purple" complex species, profile III (n=9) by high total counts and counts of Actinomyces and "purple" complex species, profile IV (n=12) by high proportions of "red" and "orange" complex species . The mean profiles of each cluster were subjected to cluster analysis with microbial data from 4380 (mean 24.7) baseline subgingival plaque samples from 27 periodontally healthy, 35 treated, well-maintained elders and 115 untreated adult periodontitis subjects . 12 clusters were formed with >41% similarity . 3 of the refractory profiles were detected in 3 cluster groups . Profile II in a cluster of 1 healthy, 1 elder and 4 untreated periodontitis subjects; profile III in a cluster of 1 healthy, 2 elder and 12 periodontitis subjects; Profile IV, with 1 healthy and 5 untreated periodontitis subjects . The profile not detected in non refractory subjects was dominated by Streptococcus species . 9 clusters did not harbor refractory profiles . 11.1% of healthy, 8.6% of elder and 18.3% of periodontitis subjects were in clusters exhibiting refractory microbial profiles . CONCLUSIONS: 4 subgingival microbial profiles were detected among refractory subjects . "Refractory microbial profiles" could be detected in subjects who had not yet exhibited refractory disease. Pharmacotherapy, 2002 Apr, 22(4), 463 - 70 Evaluation of survival and pharmacodynamic relationships for five fluoroquinolones in a neutropenic murine model of pneumococcal lung infection; Ernst EJ et al.; STUDY OBJECTIVE: To compare the antistreptococcal activity of five fluoroquinolone antibiotics, using a neutropenic murine model of pneumococcal pulmonary infection . DESIGN: Animal experiment . SETTING: University-affiliated research center . ANIMALS: Neutropenic and control mice weighing 24-29 g . INTERVENTION: After induction of neutropenia, renal failure, and infection with Streptococcus pneumoniae, the mice received one of five fluoroquinolones twice/day for 72 hours beginning 12 hours after infection . Dosages were selected to approximate 0.1 x AUC0-24 (area under the concentration-time curve from 0-24 hours) and AUC0-24 achieved in humans . Control mice received normal saline . Survival was assessed at regular intervals for up to 10 days . At least 10 mice were included in each cohort (range 10-34) . MEASUREMENTS AND MAIN RESULTS: Ciprofloxacin, clinafloxacin, grepafloxacin, levofloxacin, and moxifloxacin were studied at subtherapeutic and therapeutic dosages against three quinolone-susceptible isolates of S . pneumoniae that lacked mutations in parC, parE, and gyrA . Pharmacokinetic profile of each agent and dosing regimen was determined . A composite survival curve for all fluoroquinolones and isolates was constructed . Relationships between survival rate at 72 hours and AUC:MIC (minimum inhibitory concentration), peak:MIC, time above the MIC (percentage of dosing interval) for total and free drug concentrations were fit by using a sigmoid maximal effect (Emax) model . Survival was significantly better in the higher dosage group than in the lower dosage group . Time above MIC did not display a correlation with outcome . The AUC:MIC showed a greater correlation with outcome (R2 = 0.56 total, 0.54 free) than did peak:MIC (R2 = 0.52 total, 0.51 free) . With use of composite data, total AUC:MIC ratios associated with 50%, 90%, and 99% of Emax were 34:1, 56:1, and 95:1, respectively CONCLUSIONS: In this model, efficacy was achieved with the fluoroquinolone antibiotics at dosages yielding AUC0-24 comparable to those obtained in humans . One pharmacodynamic parameter (i.e., AUC:MIC) may be applied to various fluoroquinolones and isolates of S . pneumoniae . The AUC:MIC was more predictive of outcome than was time above the MIC or peak:MIC. Arch Pediatr, 2002 Mar, 9(3), 278 - 88 {Community-acquired pneumonia in children: etiology and treatment}; Gendrel D; Due to their very different etiological agents, community-acquired pneumoniae in children frequently require empiric antibiotic therapy in emergency . Streptococcus pneumoniae represents between 15 to 30% of the etiologies and has unspecific diagnostic procedures; as a matter of fact radiological lobar consolidation is seen in less than half of cases, and laboratory data, except for high procalcitonin level, are poorly reliable . Pneumonia due to Mycoplasma pneumoniae is frequent after 2 years of age, reaching 40 to 60% of causes in ambulatory teenagers; it must be treated with macrolides as sequellae are possible . The exact number of viral pneumonia is difficult to establish because of the lack of reliable diagnostic methods . If bacterial superinfections are probably overestimated during acute phase, viral infections may lead to bacterial pneumonia 2 to 4 weeks after the initial episode . Empiric antibiotic treatment must take into account pneumococci and their penicillin-resistant strains . Amoxicillin is the antibiotic of choice, having a higher efficacy on resistant pneumococci than oral cephalosporins . In case of clinical failure of amoxicillin, mycoplasma infection must be considered and patient must receive macrolides . Future epidemiology will be affected by anti-pneumococcal immunisation but difficulties in diagnosis and empiric antibiotic treatment will probably remain . Studies in immunised children are needed to evaluate the importance of pneumococcal infections due to serotypes not included in the vaccine. Arch Pediatr, 2002 Mar, 9(3), 262 - 5 {Varicella complicated with necrotizing fasciitis caused by group A hemolytic Streptococcus}; Billiemaz K et al.; Chickenpox has a high risk of invasive group A streptococcal disease and necroziting fasciitis . CASE REPORT: A five-year-old girl, during chickenpox treated with ibuprofen, developed sepsis and edematous and necrotic lesions of the pelvis and the abdominal wall . The child improved with surgical treatment and adjunction of clindamycin to the antibiotic therapy . CONCLUSION: We review the optimal medical and surgical treatment of necrotizing fasciitis and discuss the role of chickenpox and non steroidal antiinflammatory agents in this disease. Saudi Med J, 2002 Jan, 23(1), 99 - 103 Combined brucella melitensis and streptococcal viridans endocarditis; Al-Khuwaitir TS et al.; Infectious endocarditis is a potentially lethal inflammation of the hearts' inner lining invaded by microorganisms . The mortality from this illness increases as the number of infective organisms rises to 2, due to involvement of the left side of the heart . These microorganisms usually arise from the patient's own flora but can be acquired from the environment . Fever and heart murmurs are the principal clinical manifestations followed by a plethora of peripheral signs due to dissemination of microorganisms via the bloodstream . Echocardiographic imaging and sensitive culture techniques form the cornerstone of diagnosis . We report a patient with rheumatic heart disease who had combined brucella melitensis and streptococcus viridans endocarditis complicated by heart failure and an aortic root abscess . He was diagnosed on the basis of a history of prolonged fever and occupational risk as a shepherd, the presence of heart murmurs, positive blood cultures and echocardiographic evidence of aortic vegetations . He had an excellent response to intravenous antibiotic therapy combined with aortic valve replacement, which nowadays is regarded as the safest therapeutic approach for aortic valve endocarditis. Acta Otolaryngol, 2002 Mar, 122(2), 210 - 4 Bacteria and pathogenesis of human salivary calculus; Teymoortash A et al.; The exact cause of salivary calculus formation is unknown and the aim of this study was to ascertain whether bacteria play a role . Sialoliths from nine patients with chronic obstructive sialadenitis of the submandibular gland were analysed . Bacterial gene fragments were amplified from DNA extracted from salivary calculi by means of polymerase chain reaction using a universal bacterial primer pair . Comparative 16S ribosomal RNA sequence analysis was used for identification . We detected and identified oral bacteria (predominantly Streptococcus species) in all samples . The present results suggest a potential role for bacteria in the etiopathogenesis of sialolithiasis. FEMS Microbiol Lett, 2002 Feb 19, 208(1), 93 - 8 Chromosomal analysis of group B streptococcal clinical strains; bac gene-positive strains are genetically homogenous; Dmitriev A et al.; A collection of 45 epidemiologically unrelated Streptococcus agalactiae strains (group B Streptococcus, GBS), belonging to different serotypes, isolated from pregnant women in China and Russia was studied . Strains were characterized by pulsed-field gel electrophoresis (PFGE) employing hybridization with nine genes potentially involved in virulence . Molecular sizes of GBS genomes varied from 2030 to 2290 kb . Location of the genes under study bac, bca, glnA, scpB, cyl, hylB, lmb, scaA and cfb on the GBS genomes was found to be conserved irrelevant to the serotype . Potential virulence genes scpB, hylB, lmb were located on a 91-kb SmaI fragment that is equal to 4.5% of total genome . Ribotyping of the strains under study revealed three different HindIII, nine EcoRI and 12 PvuII ribotypes among 45 strains . A strong correlation between the PvuII ribotype and the presence of the bac gene was observed, with 21 of 22 bac-positive strains belonging to the same PvuII ribotype P1 . PFGE patterns of bac-positive strains were also similar . The possibility of close genetic relatedness of all bac-positive strains is discussed. FEMS Microbiol Lett, 2002 Feb 19, 208(1), 35 - 9 Binding of bovine lactoferrin to Streptococcus dysgalactiae subsp . dysgalactiae isolated from cows with mastitis; Park HM et al.; Three strains of Streptococcus dysgalactiae subsp . dysgalactiae (UT516, UT519, ATCC 27957) were used to determine if bovine lactoferrin (Lf) binds to bacterial cells by biotin avidin binding assay (BABA), enzyme-linked immunosorbent assay (ELISA), and binding inhibition assay . Binding assays revealed that all strains of S . dysgalactiae subsp . dysgalactiae (S . dysgalactiae) evaluated in this study bound to Lf . However, differences in Lf binding capability among strains and between methods used were detected . Binding of Lf was not inhibited by transferrin (Tf) and Lf moiety molecules (mannose, galactose, and lactose) but by Lf . This study demonstrates that S . dysgalactiae bound to bovine Lf in a specific manner. Microbes Infect, 2002 Apr, 4(4), 501 - 10 The molecular basis of Streptococcus equi infection and disease; Harrington DJ et al.; Streptococcus equi is the aetiological agent of strangles, one of the most prevalent diseases of the horse . The animal suffering and economic burden associated with this disease necessitate effective treatment . Current antibiotic therapy is often ineffective and thus recent attention has focused on vaccine development . A systematic understanding of S . equi virulence, leading to the identification of targets to which protective immunity can be directed, is a prerequisite of the development of such a vaccine . Here, the virulence factors of S . equi are reviewed. Int J Antimicrob Agents, 2002 Mar, 19(3), 219 - 26 Antimicrobial susceptibility of Streptococcus species isolated from clinical mastitis in dairy cows; Guerin-Faublee V et al.; The antimicrobial susceptibility was determined for 50 Streptococcus uberis, 42 S . dysgalactiae subsp . dysgalactiae and eight S . agalactiae strains isolated from cow mastitis . Only 27% of the strains were susceptible to all antimicrobial compounds tested . Resistance to tetracycline was most frequent (particularly for S . dysgalactiae strains), then macrolide and/or lincomycin resistance . High level resistance to streptomycin and kanamycin was detected . All S . dysgalactiae and S . agalactiae strains were susceptible to beta-lactams but 44% of the S . uberis strains showed an elevated penicillin G MIC . All strains were susceptible to chloramphenicol and rifampicin. Int J Antimicrob Agents, 2002 Mar, 19(3), 173 - 81 Comparative in-vitro activity of penicillin alone and combined with gentamicin against clinical isolates of Streptococcus pneumoniae with decreased susceptibility to penicillin; Anadiotis L et al.; The worldwide emergence of Streptococcus pneumoniae with decreased susceptibility to penicillin has led to the suggestion that drug combinations might be used . The aim of this study was to determine possible synergy using a combination of penicillin with sub-inhibitory doses of gentamicin against 26 clinical isolates of S . pneumoniae with decreased susceptibility to penicillin, using half-chequerboards and killing curves . Synergy was demonstrated for ten of the 26 isolates with the combination of penicillin with gentamicin at 1 mg/l and for 22 isolates with penicillin and gentamicin at 2 mg/l . Killing curves on three isolates showed synergy and confirmed the chequerboard results . Further synergy studies using penicillin or cefotaxime/ceftriaxone, plus low dose gentamicin against penicillin-resistant pneumococci are indicated. Am J Ophthalmol, 2002 Apr, 133(4), 463 - 6 Fourth generation fluoroquinolones: new weapons in the arsenal of ophthalmic antibiotics; Mather R et al.; PURPOSE: Fourth generation fluoroquinolones (FQs) will soon be introduced to ophthalmology . In this in vitro study, differences in the susceptibility patterns and the potencies of fourth generation FQs (gatifloxacin-GAT and moxifloxacin-MOX) were compared with third generation (levofloxacin-LEV) and second generation FQs (ciprofloxacin-CIP and ofloxacin-OFX) . DESIGN: Experimental laboratory investigation . METHODS: In retrospect, the minimum inhibitory concentrations (MICs) of 93 bacterial endophthalmitis isolates were determined to CIP, OFX, LEV, GAT, and MOX using E-tests . The National Committee of Clinical Laboratory Standards (NCCLS) susceptibility patterns and the potencies of the MICs were statistically compared . RESULTS: With in vitro tests, Staphylococcus aureus isolates that were resistant to CIP and OFX were statistically most susceptible (P =.01) to MOX . Coagulase negative Staphylococci that were resistant to CIP and OFX were statistically most susceptible (P =.02) to MOX and GAT . Streptococcus viridans were more susceptible (P =.02) to MOX, GAT, and LEV than CIP and OFX . Streptococcus pneumoniae was least susceptible (P =.01) to OFX compared with the other FQs . Susceptibilities were equivalent (P =.11) for all other bacterial groups . In general, MOX was the most potent FQ for gram-positive bacteria (P =.05) while CIP, MOX, GAT, and LEV demonstrated equivalent potencies to gram-negative bacteria . CONCLUSIONS: This in vitro study indicated that fourth generation FQs appear to cover bacterial resistance to the second and third generation FQs, were more potent than the second and third generation FQs for gram-positive bacteria, and are equally potent for gram-negative bacteria . Clinical studies will need to confirm these results. J Mol Microbiol Biotechnol, 2002 May, 4(3), 211 - 6 The ciaR/ciaH regulatory network of Streptococcus pneumoniae; Zahner D et al.; New mechanisms for beta-lactam resistance independent on the target penicillin-binding proteins were detected in beta-lactam-resistant laboratory mutants of Streptococcus pneumoniae . The link between mutations in the histidine protein kinase CiaH and phenotypic expression of cefotaxime resistance suggests that the cell is able to monitor the integrity of the cell wall and in emergency cases such as during the action of beta-lactams can counteract such danger . At least one ciaH mutation Thr230 > Pro is likely to affect its phosphatase activity resulting in elevated phosphorylation of CiaR, the cognate response regulator, but other CiaH-independent signaling pathways may also result in CiaR phosphorylation . Mutants in CiaH, either alone or in combination with a mutated penicillin-binding protein 2x(PBP2x) fail to develop genetic competence . In all cases complementation of this phenotype was observed upon addition of the competence inducing pheromone peptide CSP, the processed product of the comC gene . This indicates that the cia system is part of a regulatory network that includes another two component system comDE . The DNA binding property of CiaR and ComE were exploited to isolate specifically interacting DNA fragments as a first step to identify genes targeted by individual response regulators. Mol Microbiol, 2002 Feb, 43(3), 537 - 44 Proteolysis and its regulation at the surface of Streptococcus pyogenes; Rasmussen M et al.; Pathogenic bacteria often produce proteinases that are believed to be involved in virulence . Moreover, several host defence systems depend on proteolysis, demonstrating that proteolysis and its regulation play an important role during bacterial infections . Here, we discuss how proteolytical events are regulated at the surface of Streptococcus pyogenes during infection with this important human pathogen . Streptococcus pyogenes produces proteinases, and host proteinases are produced and released as a result of the infection . Streptococcus pyogenes also recruits host proteinase inhibitors to its surface, suggesting that proteolysis is tightly regulated at the bacterial surface . We propose that the initial phase of a S . pyogenes infection is characterized by inhibition of proteolysis and complement activity at the bacterial surface . This is achieved mainly through binding of host proteinase inhibitors and complement regulatory proteins to bacterial surface proteins . In a later phase of the infection, massive proteolytic activity will release bacterial surface proteins and degrade human tissues, thus facilitating bacterial spread . These proteolytic events are regulated both temporally and spatially, and should influence virulence and the outcome of S . pyogenes infections. Drugs, 2002, 62(5), 757 - 73 Fetal pharmacotherapy; Koren G et al.; Rapid progress has recently been encountered in pharmacologically treating the unborn baby . This unique area of drug therapy raises new methodological and ethical questions . This article is a systematic review of known modalities of fetal pharmacotherapy, and aims to highlight essential principles, difficulties and controversies in fetal pharmacotherapy . Unique pharmacokinetic features of pregnancy, the placenta and the fetus govern maternal-to-fetal drug transfer . Ethically, it is important that the mother and family are appropriately informed about the evidence in favour of specific fetal therapy, its risks and alternatives . Antenatal use of corticosteroids for lung maturation is an example of adequate methodology, leading to clear results . In contrast, the initial hopes in antenatal use of phenobarbital were based on less than optimal methodology . Folic acid for the prevention of neural tube defects is the first instance of fetal therapy that has led to the prevention of a major malformation . Serious infections, such as HIV, Group B streptococcus and toxoplasmosis highlight the need for controlled, randomised studies to prevent fetal infection . With scores of new modalities of fetal therapy likely to be introduced in the next few years, it will be important to adhere to the best possible methodology and execution, in order to address optimally the needs of the fetus. J Dairy Res, 2001 Nov, 68(4), 551 - 8 Effect of localised antibiotic infusions applied to the teat-canal and teat sinus at drying-off on mastitis in the dry-period and at calving; Woolford MW et al.; An experiment using three New Zealand herds and a total of 632 cows, examined the effect of localised prophylactic treatments with antibiotic at drying-off on the incidence of new intramammary infection during the dry period and at calving . Antibiotic was infused either into the teat canal (0.22 g of dry-cow formulation) or the teat sinus (3.1 g of lactating-cow formulation) of uninfected quarters to eliminate any bacteria present in these locations at the last milking of lactation . These treatments were compared with a negative control (nil treatment) and a positive antibiotic control (infusion of 3.6 g of dry-cow formulation) . All antibiotic formulations used the same active ingredient, sodium cloxacillin . No significant reduction in new dry period clinical mastitis was observed for the two localised treatments whereas the positive control treatment achieved 100% reduction in new clinical mastitis compared with untreated control quarters . A 41% reduction (P < 0.05) in new Streptococcus uberis infections at calving was associated with the teat canal antibiotic treatment, compared with an 82% reduction (P < 0.001) for the positive antibiotic control . Both localised treatments showed a reduced incidence of new intramammary infection (P < 0.001) when pooled across periods and pathogens . Teats receiving either the teat canal antibiotic treatment or a full infusion of long acting dry-cow antibiotic had a lower incidence of open teat canals (P < 0.05) at 3 weeks after drying-off. Ned Tijdschr Tandheelkd, 1998 Nov, 105(11), 404 - 7 {Transmission of infectious oral diseases from mother to child}; van Steenbergen TJ et al.; The relation between oral microbes of mother and child encompasses several aspects . It has been shown that a bad periodontal condition is a risk factor for low birth weight . The bacterium that is most specifically associated with dental caries, Streptococcus mutans, can be transmitted between mother and child; it has been suggested that the age of colonization with this bacterium is a risk factor for caries in the child . Also periodontal bacteria can be transmitted between mother and child . It remains to be elucidated whether this is an additional risk factor for the development of periodontal disease. EMBO J, 2002 Apr 2, 21(7), 1607 - 15 IdeS, a novel streptococcal cysteine proteinase with unique specificity for immunoglobulin G; von Pawel-Rammingen U et al.; Recent work from several laboratories has demonstrated that proteolytic mechanisms significantly contribute to the molecular interplay between Streptococcus pyogenes, an important human pathogen, and its host . Here we describe the identification, purification and characterization of a novel extracellular cysteine proteinase produced by S.pyogenes . This enzyme, designated IdeS for Immunoglobulin G-degrading enzyme of S.pyogenes, is distinct from the well-characterized streptococcal cysteine proteinase, SpeB, and cleaves human IgG in the hinge region with a high degree of specificity . Thus, other human proteins, including immunoglobulins M, A, D and E, are not degraded by IdeS . The enzyme efficiently cleaves IgG antibodies bound to streptococcal surface structures, thereby inhibiting the killing of S.pyogenes by phagocytic cells . This and additional observations on the distribution and expression of the ideS gene indicate that IdeS represents a novel and significant bacterial virulence determinant, and a potential therapeutic target. Emerg Infect Dis, 2002 Mar, 8(3), 278 - 82 A European study on the relationship between antimicrobial use and antimicrobial resistance; Bronzwaer SL et al.; In Europe, antimicrobial resistance has been monitored since 1998 by the European Antimicrobial Resistance Surveillance System (EARSS) . We examined the relationship between penicillin nonsusceptibility of invasive isolates of Streptococcus pneumoniae and antibiotic sales . Information was collected on 1998-99 resistance data for invasive isolates of S . pneumoniae to penicillin, based on surveillance data from EARSS and on outpatient sales during 1997 for beta-lactam antibiotics and macrolides . Our results show that in Europe antimicrobial resistance of S . pneumoniae to penicillin is correlated with use of beta-lactam antibiotics and macrolides. Biochem Biophys Res Commun, 2002 Apr 5, 292(3), 601 - 8 Identification and characterization of Streptococcus pneumoniae Ffh, a homologue of SRP54 subunit of mammalian signal recognition particle; Zheng F et al.; Recent studies have demonstrated that bacteria possess an essential protein translocation system similar to mammalian signal recognition particle (SRP) . Here we have identified the Ffh, a homologue of the mammalian SRP54 subunit from S . pneumoniae . Ffh is a 58-kDa protein with three distinct domains: an N-terminal hydrophilic domain (N-domain), a G-domain containing GTP/GDP binding motifs, and a C-terminal methionine-rich domain (M-domain) . The full-length Ffh and a truncated protein containing N and G domains (Ffh-NG) were overexpressed in E . coli and purified to homogeneity . The full-length Ffh has an intrinsic GTPase activity with k(cat) of 0.144 min(-1), and the K(m) for GTP is 10.9 microM . It is able to bind to 4.5S RNA specifically as demonstrated by gel retardation assay . The truncated Ffh-NG has approximately the same intrinsic GTPase activity to the full-length Ffh, but is unable to bind to 4.5S RNA, indicating that the NG domain is sufficient for supporting intrinsic GTP hydrolysis, and that the M domain is required for RNA binding . The interaction of S . pneumoniae Ffh with its receptor, FtsY, resulted in a 20-fold stimulation in GTP hydrolysis . The stimulation was further demonstrated to be independent of the 4.5S RNA . In addition, a similar GTPase stimulation is also observed between Ffh-NG and FtsY, suggesting that the NG domain is sufficient and the M domain is not required for GTPase stimulation between Ffh and FtsY. Circ J, 2002 Mar, 66(3), 305 - 7 Infected papillary fibroelastoma attached to the atrial septum; Koji T et al.; A 61-year-old woman had intermittent fever of 2 months' duration following a dental extraction . On admission, her body temperature was 39.2 degrees C . A mid-systolic murmur was heard at the apex on ausculation . A 2-dimensional echocardiogram revealed a mobile, heavy stick-like mass with vegetation (5.0 x 1.5 cm) attached to the left atrial septum . Multiple blood cultures grew Streptococcus constellatus . On diagnosis of an infected left atrial myxoma, antibiotics were administered daily and 4 weeks later, the left atrial tumor was resected . The tumor was 5.3cm long, 1.5cm in diameter at the inter-atrial wall and had vegetation on the free edge . On microscopic examination, colonies of Gram-positive cocci were found in the thrombus, on the papillary fibroelastoma . After treatment with antibiotics for a further 4 weeks, the patient was discharged . This is the first report of infected papillary fibroelastoma. MMWR Morb Mortal Wkly Rep, 2002 Mar 15, 51(10), 205 - 7 Outbreak of bacterial conjunctivitis at a college--New Hampshire, January-March, 2002; Introduction of new clones of penicillin-nonsusceptible Streptococcus pneumoniae in Hong Kong; Department of Microbiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong . margaretip@cuhk.edu.hk Analysis of penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) isolates in Hong Kong by use of a combination of antibiogram typing, serotyping, multilocus sequence typing, and pulsed-field gel electrophoresis indicated that the dissemination of PNSP was the result of the spread of international clones: variants of the Spain(23F)-1 or Spain(6B)-2 clones were the predominant PNSP isolates from 1994 to 1997 and remained so, but Taiwan(19F)-14 and Taiwan serotype 6B clones were disseminated in Hong Kong in 1999 and 2000 . Concomitant changes in antibiotic susceptibility profiles, with the rate of susceptibility to chloramphenicol rising from 10% in the period from 1994 to 1997 to 31% (P < 0.001) in 1999 and 2000, were noted to accompany the shift of clones. Indian J Med Res, 2001 Oct, 114, 127 - 32 Serotype distribution & antimicrobial resistance in Streptococcus pneumoniae causing invasive & other infections in south India; Kanungo R et al.; BACKGROUND & OBJECTIVES: Streptococcus pneumoniae continues to be a major cause of morbidity and mortality in developing countries . The emerging resistance to some common antibiotics compounds the problem . There arises a need to monitor the resistance pattern and map serotype distribution in different geographic locations . The present study was undertaken to determine the serotype prevalence and antibiotic susceptibility of clinically significant S . pneumoniae isolated from a tertiary care hospital in south India . METHODS: A total of 150 clinical isolates from invasive and other clinically significant pneumococcal infections were serotyped and screened for susceptibility to commonly used antibiotics by standard and modified laboratory procedures . RESULTS: Majority (59.3%) of the isolates belonged to one or other of the serotypes 1, 6, 19, 5, 23 and 7 . Serotype 1 was the commonest isolate from patients of meningitis and empyema followed by pneumonia . Nineteen isolates (12.6%) were nonvaccine type . Eleven (7.3%) isolates were relatively resistant to penicillin (minimum inhibitory concentration was between 0.1 and 1 microgram/ml) and 64 were resistant to one or more antibiotics . Resistance was distributed equally among the predominant serotypes . INTERPRETATION & CONCLUSION: The common serotypes responsible for significant infections were similar to those reported in some other studies from India, with minor variations . Resistance to cotrimoxazole and tetracycline was predominant followed by chloramphenicol . Low level resistance to penicillin was observed but no isolate had absolute resistance . This calls for monitoring of resistance and mapping of serotype distribution from various parts of India. Ment Retard Dev Disabil Res Rev, 2002, 8(1), 39 - 45 Public health issues related to infection in pregnancy and cerebral palsy; Schendel DE et al.; Cerebral palsy is the most common neuromotor developmental disability of childhood, affecting as many as 8,000 to 12,000 children born in the U.S . each year (corresponding to a prevalence rate of between 2 and 3 per 1000 children) . Recent improvements in neonatal care have not resulted in a decline in the overall prevalence of cerebral palsy and, in fact, greater numbers of very preterm/very low birth weight infants are surviving with cerebral palsy and other developmental problems . Infection in pregnancy may be an important cause of the disorder . In preterm infants, there appears to be about a 2-fold increased risk for cerebral palsy from chorioamnionitis, and in term infants the estimated increased risk is about 4-fold . Provisionally, chorioamnionitis might account for 12% of spastic cerebral palsy in term infants and 28% of cerebral palsy in preterm infants . Studies of biochemical markers of fetal inflammation typically associated with infection also suggest that an inflammatory response may be an important independent etiologic factor . If a substantial proportion of cerebral palsy is attributable to acute amnionitis infection and/or neonatal sepsis, cerebral palsy should have decreased in the United States after administration of intrapartum antibiotics became widespread in response to publication of public health consensus guidelines for Group B streptococcus in 1996 . However, failure to detect declines could have a number of explanations and these explanations illustrate the many public health challenges related to intrauterine infection and cerebral palsy . Given the gaps in our current knowledge about intrauterine infection and cerebral palsy, public health recommendations for timely and specific prevention activities are limited at this time . Ment Retard Dev Disabil Res Rev, 2002, 8(1), 3 - 13 Intrauterine infection and prematurity; Goncalves LF et al.; Intrauterine infection is a major cause of premature labor with and without intact membranes . Intrauterine infection is present in approximately 25% of all preterm births and the earlier the gestational age at delivery, the higher the frequency of intra-amniotic infection . Microorganisms may also gain access to the fetus before delivery . A fetal inflammatory response syndrome elicited in response to microbial products is associated with the impending onset of preterm labor and also with multi-systemic organ involvement in the human fetus and a higher rate of perinatal morbidity . The most common microorganisms involved in intrauterine infections are Ureaplasma urealyticum, Fusobacterium species and Mycoplasma hominis . The role of Chlamydia trachomatis and viruses in preterm labor remain to be determined . Use of molecular microbiology techniques to diagnose intrauterine infection may uncover the role of fastidious microorganisms that have not yet been discovered . Antibiotic administration to patients with asymptomatic bacteriuria is associated with a significant reduction in the rate of preterm birth . However, such benefit has not been demonstrated for patients with bacterial vaginosis, or women who carry Streptococcus agalactia, Ureaplasma urealyticum or Trichomonas vaginalis . Antibiotic administration to patients with preterm premature rupture of membranes is associated with prolongation of pregnancy and a reduction in the rate of clinical chorioamnionitis and neonatal sepsis . The benefit has not been demonstrated in patients with preterm labor and intact membranes . Major efforts are required to determine why some women develop an ascending intrauterine infection and others do not and also what interventions may reduce the deleterious effect of systemic fetal inflammation . J Infect Dis, 2002 Apr 1, 185(7), 927 - 36 Epub 2002 Mar 04. Reduction of nasopharyngeal carriage of Streptococcus pneumoniae after administration of a 9-valent pneumococcal conjugate vaccine to toddlers attending day care centers; Dagan R et al.; A double-blind, randomized study involving 264 toddlers attending day care centers was conducted to document the effect of a 9-valent pneumococcal conjugate vaccine on the carriage rate of pneumococci . Of 3750 cultures done on nasopharyngeal samples obtained from subjects during a 2-year follow-up period after vaccination, 65% were positive for Streptococcus pneumoniae . In all age windows, the rate of carriage of vaccine-type pneumococci was lower among subjects who received the pneumococcal vaccine than among control subjects, because the acquisition rate was lower in the former group . The effect was most pronounced among subjects aged < or =36 months . The sample size enabled us to study protection against carriage of S . pneumoniae serotypes 6B, 9V, 14, 19F, and 23F; significant protection against all serotypes except 19F was seen in the pneumococcal-vaccine group . The rate of carriage of serotype 6A (not included in the vaccine) was also reduced significantly, but the rate of carriage of serotype 19A (not included in the vaccine) was not . The rate of carriage of non-vaccine-type pneumococci (excluding serotype 6A) was higher in the pneumococcal-vaccine group than in the control group. J Infect Dis, 2002 Apr 1, 185(7), 921 - 6 Epub 2002 Mar 11. Differential effects of p38- and extracellular signal-regulated kinase mitogen-activated protein kinase inhibitors on inducible nitric oxide synthase and tumor necrosis factor production in murine macrophages stimulated with Streptococcus pneumoniae; Monier RM et al.; The role of p38- and extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase pathways in the up-regulation of inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF) production in macrophages stimulated with Streptococcus pneumoniae was examined . Inhibitors of p38 kinases effected significant decreases in the accumulation of iNOS protein in macrophages challenged with pneumococcal cell wall preparations or antibiotic-killed pneumococci, even when added up to 6 h after bacterial challenge . In contrast, ERK pathway inhibitors failed to inhibit pneumococcus-induced iNOS protein accumulation . ERK pathway inhibitors significantly reduced TNF secretion when added at the same time as pneumococcal challenge, and inhibitors of both ERK and p38 pathways reduced TNF secretion when added to the macrophages 1 h before stimulation . These data confirm the importance of the p38 and ERK MAP kinase pathways in macrophage activation by bacterial products but indicate that these 2 kinase pathways regulate different macrophage responses in a temporally distinct manner. J Feline Med Surg, 1999 Sep, 1(3), 171 - 80 Vegetative endocarditis in six cats; Malik R et al.; Between 1990 and 1997 vegetative endocarditis was diagnosed in six neutered cats (three males, three females) aged between 3 and 9 years . Two cats were purebred (one Persian and one Tonkinese), the remaining four being domestic short haired cats . The diagnosis was made using echocardiography (five cases) or at necropsy (one case) . Concurrent involvement of the aortic and mitral valve was noted in four cats, the aortic valve alone was affected in one case, and the tricuspid valve in another . A likely microbiological diagnosis was obtained in three cats: a Bartonella species in two cats based on positive blood culture and a Streptococcus species in one cat based on Gram stain of valve lesions at necropsy . In another cat, Gram-positive cocci were demonstrated histologically in tricuspid vegetations . Invariably, cats had signs of congestive heart failure (left-sided in five cats, right-sided in one), and this was the major factor contributing to mortality in four cases . Signs referable to sepsis were prominent in only two patients . Appropriate medical therapy, consisting of antimicrobials and drugs to treat congestive heart failure, resulted in survival for 5 and 11 months, respectively, in two cases . The other cats died within 2 weeks of diagnosis, including two which received aggressive treatment in hospital . Mol Microbiol, 2002 Mar, 43(5), 1161 - 72 Identification of binding sites for the group A streptococcal global regulator CovR; Federle MJ et al.; The CovRS two-component system (also called CsrRS) of the group A streptococcus (GAS) acts as a global regulator, influencing the transcription of at least six virulence factors . The synthesis of the hyaluronic acid capsule, a virulence factor encoded by the hasABC operon, is negatively regulated by CovRS . We confirmed that phosphorylation of CovR increases its binding to a DNA fragment containing the hasA promoter . Using DNase I footprinting, we identified five binding sites surrounding the hasA promoter from bases -79 to +73 (where +1 is the start of transcription) . One pair of thymines within each binding site appears to be necessary for CovR binding in vitro, as shown by uracil interference analysis . When each of these thymine pairs was altered by site-directed mutagenesis, CovR binding was reduced in vitro, confirming the role of each thymine pair in binding . Using a transcriptional reporter system with a single chromosomal copy of PhasA-gusA, we demonstrated the importance of each of four of these binding sites for CovR repression of the hasA promoter . Based on this information, we propose a consensus sequence for CovR binding to DNA. Immunology, 2002 Mar, 105(3), 344 - 9 Lipopolysaccharide triggers invasive streptococcal disease in mice through a tumour necrosis factor-alpha-dependent mechanism; Diao H et al.; Streptococcus pyogenes sometimes induces invasive streptococcal infection, including streptococcal toxic shock syndrome (STSS) . Muscular necrosis is one of the peculiar symptoms of invasive streptococcal infection and STSS . We inoculated S . pyogenes into the muscles of mice . To do so, 5 x 10(8) bacteria in 0.2 ml phosphate-buffered saline were injected into the right hind thigh . None of the mice injected with the bacteria showed muscular necrosis and none died . Tumour necrosis factor-alpha (TNF-alpha) and infiltration of leucocytes were detected in the muscles of infected sites, although the condition of the infected mice did not deteriorate after anti-TNF-alpha monoclonal antibody treatment . The infected mice treated intraperitoneally with Escherichia coli lipopolysaccharide (LPS) showed augmentation of bacterial growth, muscular necrosis and death . TNF-alpha was detected in the sera of the infected mice treated with LPS, but not in the muscles of the infected sites . Infiltration of leucocytes into the infected muscle was not observed in the infected mice treated with LPS . Anti-TNF-alpha monoclonal antibody treatment decreased mortality in the infected mice treated with LPS . Moreover, the infected mice treated with recombinant TNF-alpha showed augmentation of muscular necrosis and death . These results suggest that systemic production of TNF-alpha induced by stimulation with LPS inhibits infiltration of leucocytes into the infected site and exacerbates muscular infection, and that TNF-alpha produced in streptococcal infection is not a defence factor for the host . Invasive streptococcal infection and STSS appear to be induced by both S . pyogenes and the host's immune system. J Natl Med Assoc, 2002 Mar, 94(3), 178 - 81 It's time to step up the management of community-acquired pneumonia; Idemyor V; Optimal therapy for serious Streptococcal pneumoniae infections with intermediate or high-grade resistance to penicillin is controversial . It should be noted that data regarding the efficacy of penicillins or cephalosporins for penicillin-resistant strains are limited . Despite the paucity of clinical trials, most clinicians still agree that penicillins remain the mainstay of therapy for community-acquired pneumonia caused by Streptococcal pneumoniae-susceptible strains . Macrolide antibiotics are effective for treatment of community-acquired pneumonia caused by susceptible strains of Streptococcus pneumoniae . But resistance to all macrolides, based on current National Committee for Clinical Laboratory Standards breakpoints, should be assumed among isolates with erythromycin resistance . The late-generation fluoroquinolones have a role for treatment of community-acquired pneumonia, however, there is also the potential for evolution of antimicrobial resistance . Performance indicators for community-acquired pneumonia are being established with implementation of protocols for inpatients with pneumonia . These indicators are being monitored by the Center for Medicare and Medicaid Services (CMS) for medicare patients as part of a national project . The indicators also address documentation of influenza and pneumococcal vaccine status in patients . Several other indicators, such as obtaining blood cultures before antibiotic administration, using antibiotics according to current guidelines, and timely administration of antibiotics, will play critical roles in the management of community-acquired pneumonia . Because of increased incremental costs associated with community-acquired pneumonia, early diagnosis and timely intravenous to oral switch therapy will continue to be emphasized and monitored in those admitted into hospitals, together with the appropriate decision tree-based pneumonia specific severity of illness scoring system. Proc Natl Acad Sci U S A, 2002 Apr 2, 99(7), 4668 - 73 Epub 2002 Mar 26. Genome sequence and comparative microarray analysis of serotype M18 group A Streptococcus strains associated with acute rheumatic fever outbreaks; Smoot JC et al.; Acute rheumatic fever (ARF), a sequelae of group A Streptococcus (GAS) infection, is the most common cause of preventable childhood heart disease worldwide . The molecular basis of ARF and the subsequent rheumatic heart disease are poorly understood . Serotype M18 GAS strains have been associated for decades with ARF outbreaks in the U.S . As a first step toward gaining new insight into ARF pathogenesis, we sequenced the genome of strain MGAS8232, a serotype M18 organism isolated from a patient with ARF . The genome is a circular chromosome of 1,895,017 bp, and it shares 1.7 Mb of closely related genetic material with strain SF370 (a sequenced serotype M1 strain) . Strain MGAS8232 has 178 ORFs absent in SF370 . Phages, phage-like elements, and insertion sequences are the major sources of variation between the genomes . The genomes of strain MGAS8232 and SF370 encode many of the same proven or putative virulence factors . Importantly, strain MGAS8232 has genes encoding many additional secreted proteins involved in human-GAS interactions, including streptococcal pyrogenic exotoxin A (scarlet fever toxin) and two uncharacterized pyrogenic exotoxin homologues, all phage-associated . DNA microarray analysis of 36 serotype M18 strains from diverse localities showed that most regions of variation were phages or phage-like elements . Two epidemics of ARF occurring 12 years apart in Salt Lake City, UT, were caused by serotype M18 strains that were genetically identical, or nearly so . Our analysis provides a critical foundation for accelerated research into ARF pathogenesis and a molecular framework to study the plasticity of GAS genomes. Clin Infect Dis, 2002 Apr 15, 34(8), 1076 - 83 Epub 2002 Mar 18. A study evaluating the efficacy, safety, and tolerability of ertapenem versus ceftriaxone for the treatment of community-acquired pneumonia in adults; Ortiz-Ruiz G et al.; In a double-blind, multicenter trial, 502 patients hospitalized with community-acquired pneumonia were randomized to receive therapy with either ertapenem or ceftriaxone (for each, 1 g given intravenously once daily) . After a minimum of 3 days, therapy could be switched to oral amoxicillin-clavulanate . The median duration of intravenously administered therapy for the 383 clinically evaluable patients was 4 days for both treatment groups; 345 patients (90.1%) had their treatment switched to orally administered therapy . Of the clinically evaluable patients, 168 (92.3%) in the ertapenem group and 183 (91.0%) in the ceftriaxone group had a favorable clinical response . Streptococcus pneumoniae was the most commonly isolated pathogen, and high cure rates were observed both for penicillin-susceptible and -nonsusceptible infections in the ertapenem group (28 {87.5%} of 32 patients versus 17 {100%} of 17 patients, respectively) . Both treatment regimens were generally well tolerated; the most common drug-related adverse events reported were diarrhea (2.9% versus 2.7%) and nausea (0.8% versus 2.0%) in the ertapenem and ceftriaxone groups, respectively . These results suggest that ertapenem and ceftriaxone therapy have similar efficacy and safety in hospitalized patients with community-acquired pneumonia. Acta Crystallogr D Biol Crystallogr, 2002 Apr, 58(Pt 4), 723 - 6 Epub 2002 Mar 22. Crystallization and preliminary crystallographic studies of Streptococcus pyogenes cysteine protease precursor; Janowski R et al.; Streptococcal protease precursor, secreted by the human pathogen Streptococcus pyogenes, becomes activated to a cysteine protease . The precursor and the mature enzyme appear to contribute to S . pyogenes virulence . The precursor protein was crystallized in the form of very thin flexible flakes . X-ray diffraction data were collected to 3.15 A resolution at 100 K using synchrotron radiation . The crystals are monoclinic, space group P2(1), with unit-cell parameters a = 41.6, b = 136.0, c = 156.7 A, beta = 95.7 degrees, and contain four copies of the protein in the asymmetric unit. J Bacteriol, 2002 Apr, 184(8), 2181 - 91 Differential recognition of surface proteins in Streptococcus pyogenes by two sortase gene homologs; Barnett TC et al.; The interaction of Streptococcus pyogenes (group A streptococcus {GAS}) with its human host requires several surface proteins . In this study, we isolated mutations in a gene required for the surface localization of protein F by transposon mutagenesis of the M6 strain JRS4 . This gene (srtA) encodes a protein homologous to Staphylococcus aureus sortase, which covalently links proteins containing an LPXTG motif to the cell wall . The GAS srtA mutant was defective in anchoring the LPXTG-containing proteins M6, protein F, ScpA, and GRAB to the cell surface . This phenotype was complemented when a wild-type srtA gene was provided in trans . The surface localization of T6, however, was unaffected by the srtA mutation . The M1 genome sequence contains a second open reading frame with a motif characteristic of sortase proteins . Inactivation of this gene (designated srtB) in strain JRS4 affected the surface localization of T6 but not M6, protein F, ScpA, or GRAB . This phenotype was complemented by srtB in trans . An srtA probe hybridized with DNA from all GAS strains tested (M types 1, 3, 4, 5, 6, 18, 22, and 50 and nontypeable strain 64/14) and from streptococcal groups C and G, while srtB hybridized with DNA from only a few GAS strains . We conclude that srtA and srtB encode sortase enzymes required for anchoring different subsets of proteins to the cell wall . It seems likely that the multiple sortase homologs in the genomes of other gram-positive bacteria have a similar substrate-specific role. Eur J Clin Microbiol Infect Dis, 2002 Jan, 21(1), 43 - 5 Three cases of bacterial meningitis after spinal and epidural anesthesia; Trautmann M et al.; During a 3-year period, three cases of bacterial meningitis developing after spinal or epidural anesthesia were observed at one hospital in Germany . The causative organisms were Streptococcus salivarius (2 cases) and Staphylococcus aureus (1 case) . In the first two cases, contamination of the needle by oropharyngeal flora of the anesthesiological team was likely but remained unproven . In the third case, a nasal swab obtained from the operating anesthesiologist yielded a Staphylococcus aureus strain whose genotypic profile was identical to that of the patient's strain . Infection control procedures for spinal anesthesia are discussed. Eur J Clin Microbiol Infect Dis, 2002 Jan, 21(1), 35 - 42 Risk factors for penicillin resistance and mortality in Korean adults with Streptococcus pneumoniae bacteremia; Kim BN et al.; A retrospective analysis was performed to measure the incidence of pneumococcal bacteremia and to identify risk factors for penicillin resistance and prognostic factors for outcome in adults . A total of 151 cases of pneumococcal bacteremia were identified from 149 adults during the period 1996-2000 . The overall rate of penicillin resistance was 49%, ranging from 54.2% in 1996 to 48.5% in 2000 (P=0.93) . Rates of resistance to ceftriaxone, clindamycin, erythromycin, and trimethoprim-sulfamethoxazole were 21.6%, 51%, 62%, and 44.7%, respectively . Multidrug resistance was documented in 47.7% of the cases . Penicillin resistance was significantly associated with solid tumor, biliary drainage catheter, and previous beta-lactam therapy in the univariate analysis . However, the associations were not as significant as independent risk factors in the multivariate analysis . Mortality was 23.8% and did not change significantly during the study period (P=0.06) . Mortality rates in cases caused by penicillin-susceptible Streptococcus pneumoniae and penicillin-resistant Streptococcus pneumoniae were 23% and 24.7%, respectively (P=0.81) . Mortality was not significantly influenced by penicillin resistance, even high-level resistance (24.4% vs . 20%; P=0.64) . Multivariate analysis revealed that antineoplastic chemotherapy, respiratory failure, and acute renal failure were independent prognostic factors for mortality . In conclusion, the rate of penicillin resistance among pneumococcal blood isolates was high in the late 1990s, but penicillin resistance, and even high-level penicillin resistance, was not significantly associated with increased mortality in adults with pneumococcal bacteremia. J Cardiol, 2002 Mar, 39(3), 171 - 6 {Infective endocarditis complicating bilateral bacterial ophthalmitis: a case report}; Seno T et al.; A 53-year-old female suddenly went blind in her left eye on 3 June, 2000 . She was admitted to the Department of Ophthalmology of our hospital under the diagnosis of endophthalmitis . Her left eye was enucleated, and Streptococcus agalactiae was found in the vitreous fluid . After left ophthalmectomy, inflammation recurred after cessation of antibiotic administration . Echocardiography demonstrated a vegetation of the posterior mitral valve . The diagnosis was infective endocarditis . She was transferred to the Department of Internal Medicine . Mitral regurgitation deteriorated during the course of medical therapy, but she was discharged on 13 September, 2000 because inflammation had improved remarkably and the vegetation had disappeared after administration of penicillin G, panipenem, cefotaxime and clindamycin . We suspected that embolism of the ophthalmic artery was the cause of the sudden blindness in her left eye . Infective endocarditis with bacterial endophthalmitis is very rare in Japan. Microbiol Immunol, 2002, 46(1), 37 - 45 Chemokine production by rat macrophages stimulated with streptolysin O from Streptococcus pyogenes; Mitsui K et al.; The contribution of streptolysin O (SLO) from Streptococcus pyogenes to neutrophil infiltration in inflammatory lesions was determined by production of cytokine-induced neutrophil chemoattractant (CINC)-1, -2 and -3, and macrophage inflammatory protein (MIP)-1alpha by rat macrophages stimulated with SLO in culture . Active SLO induced the production of CINCs and MIP-1alpha in dose- and time-dependent manners . These inductions were ascertained by chemokine mRNA expression in macrophages . Streptolysin S was without effect . The SLO-cholesterol complex induced the chemokine production in proportion to the residual hemolytic activity of the complex . In addition, the effects of SLO on the chemokine production were confirmed by the injection of active SLO into the preformed air pouch on the back of rats . The infiltration of neutrophils into the pouch fluid (exudate) increased steadily with a lag phase of about 2 hr . The major chemokine found in exudates was MIP-1alpha but not CINCs . In this study, it became clear that active SLO, but not the inactive one, contributed to the production of MIP-1alpha and CINCs in the conditioned medium and in exudates. J Formos Med Assoc, 2002 Jan, 101(1), 34 - 42 Antibiotic usage in community-acquired infections in hospitals in Taiwan; Ho M et al.; BACKGROUND AND PURPOSE: Using an epidemiologically meaningful in-hospital population with community-acquired infections, we evaluated antibiotic therapy in terms of indication and choice of antibiotic and microbiologic work-up . METHODS: Infectious disease specialists evaluated charts of 436 patients from 9 hospitals and selected those who received antibiotics within 3 days of admission . Each antibiotic prescribed was marked for appropriateness of indication and choice . Microbiologic isolates were evaluated for their clinical significance . RESULTS: The most common infections were in the lower respiratory tract (46.1%) . Each patient received a mean of 2.25 antibiotics for 8.1 +/- 6.4 days . Of the 975 courses of antibiotics given in the study period, indication and choice were correct in 37.4% and unsatisfactory in 14.5% . The vast majority of antibiotics used (79.2%) were first-line antibiotics--usually first-generation cephalosporins, aminoglycosides, and aminopenicillins . Most patients (66%) had a microbiology laboratory work-up, but only 37.4% were judged by evaluators to have a meaningful microbiologic diagnosis . Among the 201 patients with lower respiratory tract infections, 105 (52.2%) had a diagnosis of pneumonia . A positive isolate was recovered in 30 (28.6%) patients, and most of these isolates (20, 68.7%) were aerobic gram-negative rods . There were three positive blood cultures but none grew Streptococcus pneumoniae . CONCLUSIONS: Antibiotics were used excessively in number and duration . The microbiologic work-up had little effect on the indication and choice of antibiotics . Community-acquired pneumonia differed markedly from that in Western countries in that only 3.3% were caused by S . pneumoniae. J Antimicrob Chemother, 2002 Apr, 49(4), 671 - 4 In vitro bactericidal activity of ABT-773 and amoxicillin against erythromycin-susceptible and -resistant strains of Streptococcus pyogenes; Pendland SL et al.; The bactericidal activity of ABT-773 was compared with amoxicillin against 10 clinical isolates of S . pyogenes (six erythromycin susceptible and four erythromycin resistant) . The MIC ranges (mg/L) were 0.004-0.25 of ABT-773 and 0.015-0.12 of amoxicillin . At 24 h, ABT-773 concentrations of 2 x MIC and 8 x MIC were bactericidal against three and six organisms, respectively . In comparison, amoxicillin was bactericidal against all 10 organisms at both test concentrations. Abdom Imaging, 2001 Nov-Dec, 26(6), 651 - 3 Successful treatment of a ruptured mycotic aneurysm of the ileocolic artery with transcatheter embolization and antibiotic therapy; Poletti PA et al.; We report a case of mycotic aneurysm of the ileocolic artery due to Streptococcus bovis endocarditis and acute septicemia complicated by active hemorrhage, that was treated successfully with transcatheter embolization and subsequent intravenous antibiotic treatment . This case suggests that a mycotic aneurysm can be treated successfully by percutaneous embolization in an emergent situation (active bleeding, septicemia) even without previous antibiotic therapy. J Immunol, 2002 Apr 1, 168(7), 3507 - 11 Urokinase receptor is necessary for adequate host defense against pneumococcal pneumonia; Rijneveld AW et al.; Cell recruitment is a multistep process regulated by cytokines, chemokines, and growth factors . Previous work has indicated that the urokinase plasminogen activator receptor (uPAR) may also play a role in this mechanism, presumably by an interaction with the beta(2) integrin CD11b/CD18 . Indeed, an essential role of uPAR in neutrophil recruitment during pulmonary infection has been demonstrated for beta(2) integrin-dependent respiratory pathogens . We investigated the role of uPAR and urokinase plasminogen activator (uPA) during pneumonia caused by a beta(2) integrin-independent respiratory pathogen, Streptococcus pneumoniae . uPAR-deficient (uPAR(-/-)), uPA-deficient (uPA(-/-)), and wild-type (Wt) mice were intranasally inoculated with 10(5) CFU S . pneumoniae . uPAR(-/-) mice showed reduced granulocyte accumulation in alveoli and lungs when compared with Wt mice, which was associated with more S . pneumoniae CFU in lungs, enhanced dissemination of the infection, and a reduced survival . In contrast, uPA(-/-) mice showed enhanced host defense, with more neutrophil influx and less pneumococci in the lungs compared with Wt mice . These data suggest that uPAR is necessary for adequate recruitment of neutrophils into the alveoli and lungs during pneumonia caused by S . pneumoniae, a pathogen eliciting a beta(2) integrin-independent inflammatory response . This function is even more pronounced when uPAR is unoccupied by uPA. J Immunol, 2002 Apr 1, 168(7), 3437 - 43 Gamma 3 gene-disrupted mice selectively deficient in the dominant IgG subclass made to bacterial polysaccharides . II . Increased susceptibility to fatal pneumococcal sepsis due to absence of anti-polysaccharide IgG3 is corrected by induction of anti-polysaccharide IgG1; McLay J et al.; Bacterial polysaccharides (PS) are type 2 T-independent Ags that elicit Abs restricted in isotype to IgM and predominantly IgG2 in humans and IgM, and IgG3 in mice . Humans with IgG2 subclass deficiency are susceptible to sinus and pulmonary infections with PS-encapsulated bacteria . We previously developed an IgG3-deficient mouse by disrupting the gamma3 H chain constant region gene via targeted mutagenesis . Mutant mice lacking IgG3 were backcrossed for 10 generations to wild-type (WT) BALB/c mice to generate BALB/c mice that have complete absence of IgG3 . WT mice immunized with type 3 Streptococcus pneumoniae capsular PS made anti-PS IgM, IgG3, and small quantities of IgG1, which opsonized S . pneumoniae for killing by polymorphonuclear leukocytes . These mice were protected against death from lethal doses of type 3 S . pneumoniae . In contrast, IgG3(-/-) mice made similar titers of anti-PS IgM and IgG1 as WT mice but no IgG3, and had poorly opsonic sera with significantly increased mortality after S . pneumoniae challenge . Immunization of IgG3(-/-) mice with type 3 S . pneumoniae PS conjugated to carrier protein CRM(197)-elicited IgM and high-titer IgG1 Abs, restored serum opsonization, and gave protection from mortality after S . pneumoniae, challenge comparable to WT mice . We conclude that mice lacking the dominant IgG3 subclass made to bacterial PS are more susceptible to fatal S . pneumoniae sepsis than WT mice, but that IgG1 induced by a S . pneumoniae glycoconjugate can adequately protect against S . pneumoniae sepsis . This model suggests that IgG subclass of anti-PS Ab is an important component of immunity to encapsulated bacteria. Mol Microbiol, 1997 Jul, 25(1), 79 - 92 Molecular organization of the genes required for the synthesis of type 1 capsular polysaccharide of Streptococcus pneumoniae: formation of binary encapsulated pneumococci and identification of cryptic dTDP-rhamnose biosynthesis genes; Munoz R et al.; We report here the molecular organization of the capsular locus (cap1) of the type 1 pneumococcus . This locus is located between dexB and aliA and flanked by IS1167 insertion elements . Sequence analysis showed that the cluster contains 11 genes (cap1A to cap1K), which are apparently arranged as a single transcriptional unit . The presence of a functional promoter (cap1p) located upstream of cap1A has been demonstrated and the transcription start point was mapped by primer-extension analysis . A 14.3 kb fragment containing the genes cap1ABCDEFGHIJK and including cap1p was sufficient to allow the synthesis of a type 1 capsule in Streptococcus pneumoniae . An internal deletion of cap1E leads to an unencapsulated phenotype demonstrating that this gene is essential for capsular production . The cap1K gene has been expressed in Escherichia coli resulting in UDP-glucose dehydrogenase (UDP-GlcDH) activity . Moreover, this gene was able to restore the synthesis of type 3 capsule when cloned into a plasmid and introduced by transformation into S . pneumoniae cap3A mutants deficient in UDP-GlcDH . In marked contrast with what was previously thought, recombination between cap1K and cap3A does occur . We provide data on the molecular mechanism that leads to the formation of binary encapsulated pneumococcal cells, i.e . strains that simultaneously produce type 1 and type 3 capsules . Downstream of cap1K, one truncated and three complete open reading frames homologous to those involved in the biosynthesis of dTDP-rhamnose, a monosaccharide that does not participate in the formation of type 1 polysaccharide, have been identified in all the clinical strains of type 1 pneumococcus tested . Our results provide new insights into the generation of capsule diversity in pneumococci. Chemotherapy, 2002 Mar, 48(1), 26 - 30 Evaluation of the new VITEK 2 system for determination of the susceptibility of clinical isolates of Streptococcus pneumoniae; Chavez M et al.; BACKGROUND: The VITEK 2 is a new version of the automated system for organism identification and susceptibility testing . One of the differences between this system and its predecessor, VITEK, is the ability to perform rapid susceptibility testing of Streptococcus pneumoniae . This study compares the results of susceptibility testing of S . pneumoniae using the VITEK 2 system and a commercial microbroth dilution method, Sensititre . METHODS: A group of 214 clinical isolates of S . pneumoniae were selected to include isolates with previously documented penicillin resistance . The antimicrobial agents tested were benzylpenicillin, cefotaxime, erythromycin, trimethoprim/sulfamethoxazole, tetracycline, chloramphenicol, imipenem and vancomycin . RESULTS: The best agreement was achieved with vancomycin (100%), erythromycin (95.8%) and tetracycline (95.8%) . The lowest level of agreement was found with benzylpenicillin (88.6%) and cefotaxime (90.1%) . We observed rates of 12.3 and 15.7% for minor errors with penicillin and cefotaxime, respectively, and 1 very major error for cefotaxime . CONCLUSION: The VITEK 2 allows rapid determination of the antimicrobial susceptibility of S . pneumoniae and demonstrated a good degree of agreement with the Sensititre method for most of the antimicrobials tested . Copyright 2002 S . Karger AG, Basel Publication Types:
|
© 2005
Transgalactic Ltd (manufacturer of Bioscreen C software) |
Privacy Statement | P.O. Box
1393, 00101 Helsinki, Finland,
Last modified: May 25, 2005
| ||||||
