Streptococci

Eur J Clin Microbiol Infect Dis, 2004 Nov, 23(11), 818 - 24 Epub 2004 Nov.
Identification and immunoreactivity of proteins released from Streptococcus agalactiae; Fluegge K et al.; The aim of the present study was to identify released proteins of Streptococcus agalactiae and to investigate their immunoreactivity with human sera to determine whether such proteins might be viable as carrier proteins in conjugate vaccines . Infections with S . agalactiae are the leading cause of sepsis and meningitis in neonates . Vaccination of women of childbearing age would be a desirable alternative to intrapartum antibiotic prophylaxis, but factors that mediate S . agalactiae invasive disease and virulence are poorly defined . Capsule-based vaccines have shown only low immunogenicity to date, and interest has shifted towards S . agalactiae proteins, either as candidate vaccine antigens or as carrier proteins for serotype-specific S . agalactiae polysaccharides . In this study, some major released proteins of S . agalactiae could be identified, including molecules known to be present on the surface of bacterial cells but not previously described as released proteins, such as CAMP factor, a phosphocarrier protein, aldolase, enolase, PcsB, and heat-shock protein 70 . Serotype-specific differences in the protein patterns of extracellular products and immunoreactivity with human sera could be detected by SDS-PAGE and Western blot . The identification of unexpected released proteins may indicate secondary functions for these proteins . In addition, the widespread immunoreactivity of these proteins with human sera as shown by Western blot indicates that released proteins may be promising candidates as carrier proteins in conjugate vaccines.

J Bacteriol, 2004 Nov, 186(21), 7100 - 11
Four proteins encoded in the gspB-secY2A2 operon of Streptococcus gordonii mediate the intracellular glycosylation of the platelet-binding protein GspB; Takamatsu D et al.; Platelet binding by Streptococcus gordonii strain M99 is mediated predominantly by the cell surface glycoprotein GspB . This adhesin consists of a putative N-terminal signal peptide, two serine-rich regions (SRR1 and SRR2), a basic region between SRR1 and SRR2, and a C-terminal cell wall anchoring domain . The glycosylation of GspB is mediated at least in part by Gly and Nss, which are encoded in the secY2A2 locus immediately downstream of gspB . This region also encodes two proteins (Gtf and Orf4) that are required for the expression of GspB but whose functions have not been delineated . In this study, we further characterized the roles of Gly, Nss, Gtf, and Orf4 by investigating the expression and glycosylation of a series of glutathione S-transferase-GspB fusion proteins in M99 and in gly, nss, gtf, and orf4 mutants . Compared with fusion proteins expressed in the wild-type background, fusion proteins expressed in the mutant strain backgrounds showed altered electrophoretic mobility . In addition, the fusion proteins formed insoluble aggregates in protoplasts of the gtf and orf4 mutants . Glycan detection and lectin blot analysis revealed that SRR1 and SRR2 were glycosylated but that the basic region was unmodified . When the fusion protein was expressed in Escherichia coli, glycosylation of this protein was observed only in the presence of both gtf and orf4 . These results demonstrate that Gly, Nss, Gtf, and Orf4 are all involved in the intracellular glycosylation of SRRs . Moreover, Gtf and Orf4 are essential for glycosylation, which in turn is important for the solubility of GspB.

J Bacteriol, 2004 Nov, 186(21), 7091 - 9
Rgg regulates growth phase-dependent expression of proteins associated with secondary metabolism and stress in Streptococcus pyogenes; Chaussee MA et al.; The transcriptional regulatory protein Rgg coordinates amino acid catabolism and virulence factor expression in Streptococcus pyogenes . We used a proteomic approach to compare cytoplasmic proteins isolated from S . pyogenes wild-type strain NZ131 (serotype M49) to proteins isolated from an rgg mutant strain during the exponential and stationary phases of growth . Proteins were separated by two-dimensional gel electrophoresis, and 125 protein spots of interest were identified by tandem mass spectrometry . Comparative analysis of proteins isolated from the isogenic strains revealed that growth phase-associated regulation of enzymes involved in the metabolism of arginine (ArcABC), histidine (HutI), and serine (SdhA) was abrogated in the rgg mutant strain, which synthesized the proteins in the exponential phase of growth . In contrast, the enzymes were detected only among wild-type proteins isolated from organisms in the stationary phase of growth . The differences in protein composition were correlated with previously described metabolic changes . In addition, proteins associated with thermal and oxidative stress responses, including ClpE and ClpL, were present in samples isolated from the rgg mutant strain but not in samples isolated from the wild-type strain . The rgg mutant strain was more tolerant to elevated temperature and puromycin than the wild-type strain; however, the mutant was less tolerant to paraquat . We concluded that Rgg is a global regulatory factor that contributes to growth phase-dependent synthesis of proteins associated with secondary metabolism and oxidative and thermal stress responses.

J Antimicrob Chemother, 2004 Dec, 54(6), 1148 - 51 Epub 2004 Oct 15.
Bactericidal activity of amoxicillin against non-susceptible Streptococcus pneumoniae in an in vitro pharmacodynamic model simulating the concentrations obtained with the 2000/125 mg sustained-release co-amoxiclav formulation; Sevillano D et al.; OBJECTIVES: To investigate the bactericidal activity against Streptococcus pneumoniae of simulated amoxicillin serum concentrations obtained in humans after 2000/125 mg sustained-release (SR) and 875/125 mg co-amoxiclav administered twice and three times a day, respectively . METHODS: An in vitro computerized pharmacodynamic simulation was carried out and colony counts were determined over 24 h . Ten strains non-susceptible to amoxicillin (four of them exhibiting an MIC of 4 mg/L, five strains with an MIC of 8 mg/L and one strain with an MIC of 16 mg/L) were used . RESULTS: With amoxicillin 2000 mg, an initial inoculum reduction >99.99% was obtained for strains with an MIC of 4 mg/L, >/=99% for strains with an MIC of 8 mg/L and 70.6% for the strain with an MIC of 16 mg/L at 24 h sampling time . At this sampling time, no reduction of initial inocula was obtained with amoxicillin 875 mg/8 h for two of the four strains with an MIC of 4 mg/L, three of the five strains with an MIC of 8 mg/L or for the strain with an MIC of 16 mg/L . CONCLUSIONS: The new co-amoxiclav 2000/125 mg SR formulation appears to offer advantages versus previous formulations with respect to bactericidal activity against current amoxicillin non-susceptible strains.

Int J Pediatr Otorhinolaryngol, 2004 Nov, 68(11), 1435 - 9
Acute mastoiditis in infancy: the Soroka experience: 1990-2000; Niv A et al.; Acute mastoiditis (AM) is an uncommon but serious complication of acute otitis media (AOM) . In the pre-antibiotic era, AM was seen more frequently than it is today, but it was rare in infants . However, in the last two decades an increase in the incidence of AM in infancy has been reported in the literature . During the years 1990-2002, we treated 113 patients with 128 episodes of AM; of them, 24 were infants (median age 6 months; 18 males) who suffered from 26 episodes of AM . Twenty developed AM as a complication of their first episode of AOM . One of the four infants with a prior history of AOM suffered from common variable immunodeficiency . A significant increase in the incidence of AM in infants was recorded during the study period (P = 0.01) . The most common presenting clinical signs were post-auricular swelling and fever >38 degrees C (77% and 77%, respectively, of all patients) . Seventeen episodes of AM were not treated with prior antibiotics . Tympanocentesis was performed in all episodes of AM . Middle ear fluid culture was positive in 17 (65%) of the 26 AM episodes . The most common pathogens cultured were Streptococcus pneumoniae (10 infants, 58% of all pathogens, 3/10 intermediately susceptible to penicillin) followed by Streptococcus pyogenes (4, 23%), non-typable H . influenzae (2, 12%) and S . aureus (1, 6%) . Temporal bone CT showed bone destruction in 14 patients; 3 infants had subperiosteal abscesses and 3 lateral sinus thrombosis . Ten infants underwent mastoid surgery due to non-resolution of symptoms and signs with antibiotic therapy . Eight underwent cortical mastoidectomy with two patients undergoing ventilation tube introduction only . The remainder of the infants healed with conservative treatment . Conclusions: (1) A significant increase in the incidence of AM in infants was recorded over the last decade, though a specific reason for this trend remains uncertain; (2) Most of the cases of AM followed the infant's initial AOM episode, and most of the infants had not received prior antibiotic therapy; (3) The clinical signs and symptoms of AM were more severe in infants than in older patients; (4) While S . pneumonia was the most common pathogen isolated in middle ear fluid cultures, the involvement of S . pyogenes in AM was higher than that reported in AOM.

Microbes Infect, 2004 Nov, 6(13), 1156 - 62
The fibronectin-binding capacity and host cell adherence of Streptococcus pyogenes strains are discordant with each other; Edwards ML et al.; Surface exposed fibronectin-binding proteins (FBPs) play an important role in the adherence of Streptococcus pyogenes (group A streptococcus, GAS) to host cells . This pathogen expresses numerous FBPs, of which SfbI, SfbII and PrtF2 are major surface exposed FBPs . However, GAS strains differ in the genetic potential to express these proteins . To test whether this difference reflects in differences in fibronectin (Fn) binding, a set of circulating strains previously examined for adherence to host cells was used . The 68 distinct strains were isolated from throat, skin and blood . They were analyzed for (a) the presence of genes for SfbI, SfbII and PrtF2 and (b) the extent of Fn binding . The results suggest that strains possessing two or more of the genes for these FBPs bound Fn significantly more than strains possessing none or one of the genes . No correlation between the extent of Fn binding and the tissue site of isolation was found . Furthermore, together with our previous studies on adherence capacity of these GAS strains, we found no correlation between Fn binding ability and the avidity of the strains to adhere to epithelial cells . We suggest that while Fn binding is important for adhesion, for many GAS strains the extent of Fn binding is not the critical determinant of adherence.

Clin Infect Dis, 2004 Oct 15, 39(8), 1148 - 54 Epub 2004 Sep 27.
An outbreak of conjunctivitis due to a novel unencapsulated Streptococcus pneumoniae among military trainees; Crum NF et al.; BACKGROUND: Bacterial conjunctivitis usually occurs as sporadic cases; outbreaks are uncommon and usually are associated with school campuses . We report an outbreak of Streptococcus pneumoniae conjunctivitis at a military training facility . METHODS: An outbreak investigation was done . Each case of conjunctivitis was evaluated with an assessment tool including demographic and clinical data . Conjunctival swabs were obtained . Pneumococci underwent standard testing, including serotyping with the Quellung reaction, capsular staining, and multilocus sequence typing . Sequence types were compared with previous reported outbreak strains by construction of dendrograms . Carriage rates of S . pneumoniae were determined among previously undiagnosed case patients with conjunctivitis, and a case-control study was performed . Control measures included education to increase hand washing, distribution of alcohol-based hand gel, and prompt treatment of patients with conjunctivitis . RESULTS: During a 6-week period, 92 cases of conjunctivitis occurred among 3500 persons, with an attack rate of 1.75 cases per 100 person-months . Eighty cases (87%) were due to S . pneumoniae; 45 (49%) were confirmed, and 35 (38%) were probable . Ten percent of recruits surveyed carried the outbreak strain . Twenty-two percent self-reported symptoms consistent with conjunctivitis during the outbreak period; sharing washcloths was associated with conjunctivitis (odds ratio, 11.7; P=.03) . The causative organism was resistant to azithromycin but susceptible to telithromycin . The outbreak strain was an unencapsulated S . pneumoniae that has not been previously described; it was most closely related to the sequence type causing the Dartmouth College (Hanover, NH) outbreak of conjunctivitis in 2002 . CONCLUSIONS: We report a conjunctivitis outbreak among military trainees caused by a novel, unencapsulated strain of S . pneumoniae.

Clin Infect Dis, 2004 Oct 15, 39(8), 1129 - 35 Epub 2004 Sep 14.
Multicenter study of a rapid molecular-based assay for the diagnosis of group B Streptococcus colonization in pregnant women; Davies HD et al.; BACKGROUND: Current prevention of infection due to group B Streptococcus (GBS) involves giving intrapartum antibiotics to women on the basis of either antenatal culture colonization status or presence of risk factors . METHODS: We prospectively compared the performance characteristics of a rapid molecular diagnostic test (IDI-Strep B; Infectio Diagnostic) with culture for intrapartum GBS detection after 36 weeks' gestation in 5 North American centers during the period September 2001-May 2002 . Antenatal GBS screening was done according to the usual practice of participating hospitals . Two combined vaginal/anal specimens were obtained from participants during labor by use of standard techniques and processed by the same laboratories that processed the antenatal specimens . Each swab sample was processed simultaneously by culture and with IDI-Strep B . The collected specimens were randomized for order of testing of the swab samples by culture or the rapid test . RESULTS: Of enrolled women, 803 (91.1%) were eligible for analysis . The overall intrapartum GBS colonization rate by culture was 18.6% (range, 9.1%-28.7%) . Compared with intrapartum culture, the molecular test had a sensitivity of 94.0% (range, 90.1%-97.8%), specificity of 95.9% (range, 94.3%-97.4%), positive predictive value of 83.8% (range, 78.2%-89.4%), and negative predictive value of 98.6% (range, 97.7%-99.5%) . The molecular test was superior to antenatal cultures (sensitivity, 94% vs . 54%; P<.0001) and prediction of intrapartum status on the basis of risk factors (sensitivity, 94% vs . 42%; P<.0001) . CONCLUSION: Use of this test for determination of GBS colonization during labor is highly sensitive and specific and may lead to a further reduction in rates of neonatal GBS disease.

Curr Microbiol, 2004 Nov, 49(5), 366 - 71
Molecular characterization and transcription of the luxS gene that encodes LuxS autoinducer 2 synthase in Streptococcus bovis; Asanuma N et al.; Presence of the luxS gene that encodes LuxS autoinducer 2 (AI-2) synthase in Streptococcus bovis was demonstrated, and the molecular properties and transcription of the gene were examined . The S . bovis luxS was transcribed in a monocistronic fashion . Intracellular luxS-mRNA increased sharply during the initial exponential growth, and decreased abruptly after the middle exponential phase . The large drop in luxS transcription began before the glucose supply to cells decreased or the growth rate declined . Transcription of luxS was not directly related to cell density, and continued at a maximal rate when cells were kept growing at a maximal rate . It is conceivable that AI-2 activity in S . bovis acts as a signal for adjusting cell physiology and metabolism in response to environmental conditions . However, the role of LuxS in S . bovis, including the regulation of AI-2 synthesis,, remains to be clarified.

J Antimicrob Chemother, 2004 Dec, 54(6), 1067 - 71 Epub 2004 Oct 14.
Pulsatile delivery of amoxicillin against Streptococcus pneumoniae; Cha R et al.; OBJECTIVE: beta-Lactam antimicrobials are dosed intermittently or continuously based on their short half-lives and concentration-independent activity . Based on the relationship between antimicrobial killing and bacterial growth cycle, the pharmacodynamics of a unique pulsatile strategy was investigated . METHODS: In vitro pharmacodynamic models with initial inocula of 6 log(10) cfu/mL were utilized to simulate amoxicillin regimens against two Streptococcus pneumoniae isolates: 16891 (MIC = 4 mg/L) and ATCC 49150 (MIC = 0.016 mg/L) . Time-kill profiles of pulsatile dosing of amoxicillin (total daily dose fractionated equally and given at 0, 2, 4 and 6 h for each 24 h cycle) were compared with regimens of every 8 h and every 12 h with the same 24 h drug exposure . Each regimen targeted cumulative peak concentrations of 30, 15 and 5 mg/L for each 24 h cycle . A t(1/2) of 1 h was simulated for all experiments . Bacterial density was quantified over 96 h . RESULTS: Against 16891, every 8 h and every 12 h regimens exhibited minimal bacterial kill at all dosing levels . In contrast, pulsatile dosing at 30 mg/L/24 h resulted in an initial modest approximately 1 log(10) cfu/mL kill with regrowth to growth control levels at 24 h but was immediately followed by a rapid approximately 2 log(10) cfu/mL kill by 32 h . This pattern of kill and regrowth repeated at the same magnitude for each 24 h cycle for the 96 h study duration . Against the susceptible strain (ATCC 49150), both pulse and traditional dosing of amoxicillin resulted in rapid and significant kill to our detection limits for the entire study duration . A pattern of kill and regrowth was only observed at the lowest dose (0.05 mg/L) against ATCC 49150 . At therapeutic levels, all regimens rapidly achieved undetectable limits against this strain for the study duration . No significant alterations in post-exposure MICs were noted . Overall bacterial density reduction was similar between the regimens for the susceptible isolate and greater with pulsatile regimens against the less susceptible strain . CONCLUSION: Pulsatile dosing, which involves administration of the total daily dose over the first 6 h of the day, may represent a unique and alternative strategy for dosing beta-lactam antimicrobials.

J Biol Chem, 2004 Dec 17, 279(51), 53241 - 7 Epub 2004 Oct 13.
Streptococcus pneumoniae-induced p38 MAPK-dependent phosphorylation of RelA at the interleukin-8 promotor; Schmeck B et al.; Streptococcus pneumoniae is the major cause of community-acquired pneumonia and one of the most common causes of death by infectious disease in industrialized countries . Little is known concerning the mechanisms of target cell activation in this disease . The present study shows that NF-kappaB and p38 MAPK signaling pathways contribute to chemokine synthesis by lung epithelial cells in response to pneumococci . In infected lungs of mice pneumococci stimulate expression of the interleukin (IL)-8 homolog keratinocyte-derived chemokine and granulocyte-macrophage colony-stimulating factor, as well as activate p38 MAPK . Human bronchial epithelium was chosen as a cellular model, because it establishes the first barrier against pathogens, and little is known about its function in innate immunity . Pneumococci infection induces expression of IL-8 and granulocyte-macrophage colony-stimulating factor as well as activation of p38 MAPK in human bronchial epithelial cells (BEAS-2B) . Inhibition of p38 MAPK activity by SB202190 and SB203580 blocks pneumococci-induced cytokine release . In mouse lungs in vivo as well as in cultured cells, pneumococci activate NF-kappaBinanIkappaB kinase-dependent manner . Inhibition of p38 MAPK by chemical inhibitors or by RNA interference targeting p38alpha reduces pneumococci-induced NF-kappaB-dependent gene transcription . Blockade of p38 activity did not affect inducible nuclear translocation and recruitment of NF-kappaB/RelA to the IL-8 promotor but did reduce the level of phosphorylated RelA (serine 536) at IL-8 promotor and inhibited pneumococci-mediated recruitment of RNA polymerase II to IL-8 promotor . Thus, p38 MAPK contributes to pneumococci-induced chemokine transcription by modulating p65 NF-kappaB-mediated transactivation.

Infect Control Hosp Epidemiol, 2004 Sep, 25(9), 759 - 64
Pattern of culture-proven neonatal sepsis in a district general hospital in the United Kingdom; Haque KN et al.; OBJECTIVE: To determine the incidence, clinical characteristics, and risk factors associated with the first culture-proven episode of sepsis among neonates in a neonatal intensive care unit (NICU) . SETTING: Level-II NICU in the United Kingdom . PATIENTS: Neonates with their first culture-proven sepsis between January 1, 1996, and December 31, 2000 . METHODS: Demographic data were obtained from the NICU database and chart review . Sepsis was considered early (EOS; < 72 hours old) or late (LOS; > 72 hours old) . Data were also collected on potential risk factors . RESULTS: Among 14,767 live births, 1,612 (11%) neonates were admitted to the NICU during the study period . Nine hundred eight were screened for sepsis . One hundred twenty-four had at least one positive culture (overall sepsis rate of 8.4 per 1,000 live births {1%} or 77 per 1,000 NICU admissions) . Twenty-four neonates had EOS and 100 had LOS . Coagulase-negative staphylococci (CoNS) and group B Streptococcus were the most frequent organisms causing EOS, whereas CoNS and Escherichia coli most frequently caused LOS . Birth before 30 weeks' gestation and birth weight less than 1,500 g were risk factors for sepsis . Resuscitation at birth was the leading risk factor for EOS and respiratory support prior to sepsis, presence of a central or peripheral catheter, and total parenteral nutrition were leading risk factors for LOS . CONCLUSIONS: A strong inverse relationship existed between gestational age of 30 weeks or younger and birth weight of 1,500 g or less and LOS . Resuscitation and indwelling intravenous catheters were also risk factors.

J Korean Med Sci, 2004 Oct, 19(5), 735 - 8
Detection rates of bacteria in chronic otitis media with effusion in children; Park CW et al.; This study was performed to investigate polymerase chain reaction-based detection of bacterial DNA in middle ear fluid and assess the correlation between the PCR-positive rate with several factors associated with middle ear effusion . The purpose was to gain a further understanding of bacterial infection as a major cause of otitis media with effusion . Of the 278 specimens of middle ear fluid, 39 (14%) tested positive by ordinary culture . The overall detection rate of bacterial DNA using the PCR method was 36.7% for middle ear effusion, and bacterial DNA detection rates of Hemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis in the middle ear effusion were 29.1%, 4.7% and 10.8%, respectively . The bacterial DNA detection rate was higher in ears with a history of acute otitis media than those without the history . High detection rates were observed in patients younger than 48 months who have had a higher tendency to present with acute otitis media . We concluded that PCR is a more sensitive method for the detection of bacteria in middle ear effusion than ordinary culture, and acute otitis media is a major contributor to the pathogenesis of otitis media with effusion.

Zhonghua Er Ke Za Zhi, 2004 Sep, 42(9), 697 - 700
{In vitro antibacterial activity of cefdinir against isolates of respiratory tract pathogens in children}; Lu Q et al.; OBJECTIVE: To study the in vitro antibacterial activity of cefdinir against clinical isolates of respiratory tract pathogens in Children . METHODS: MIC values of cefdinir against 380 strains were determined with E-test method and compared with those of cefaclor . RESULTS: All penicillin-susceptible Streptococcus pneumoniae (PSSP) strains were also susceptible to cefdinir and cefaclor . Both cefdinir and cefaclor were not active against penicillin-resistant SP (PRSP) . Against penicillin-intermediate SP (PISP) the susceptibility rates of cefdinir and cefaclor were 70.1% and 57.4%, respectively . The activity of cefdinir and cefaclor against beta-lactamases negative Hemophilus influenzae (HI) was excellent, but the susceptibility rates of cefdinir and cefaclor against beta-lactamases positive HI were 85.0% and 70.0%, respectively with MIC(90) of 1.5 mg/L vs . 256.0 mg/L . Cefdinir presented higher activities and lower MIC values than cefaclor against Moraxella catarrhalis (MC), Group A streptococcus (GAS), methicillin susceptible staphylococcus aureus (MSSA), and extended spectrum beta-lactamases (ESBLs) negative Escherichia coli (E . coli) or Klebsiella pneumoniae (K . pn) . Both cefdinir and cefaclor were not susceptible to ESBLs positive E . coli and K . pn . CONCLUSIONS: Cefdinir exhibits excellent activity against PSSP, PISP, HI, as well as MC, GAS, MSSA and ESBLs negative E . coli or K . pn.

Expert Rev Anti Infect Ther, 2004 Jun, 2(3), 427 - 37
Significance, management and prevention of Streptococcus agalactiae infection during the perinatal period; Berner R; The highest annual death rate during the first five decades of life occurs in the first year, particularly during the perinatal period between the onset of labor and 72 h after birth . Invasive bacterial disease evoking the severe inflammatory response syndrome is a leading cause of perinatal morbidity and mortality . Group B streptococcus (Streptococcus agalactiae) is the most important pathogen in this period of life, although the concept of intrapartum antimicrobial prophylaxis has impressively reduced the rate of culture-proven invasive infection in neonates . This strategy, however, has considerable limitations since group B streptococcus-related stillbirths or prematurity and late-onset sepsis cannot be prevented . Moreover, the use of intrapartum antimicrobial prophylaxis has significantly increased the use of antibiotics during labor and therefore may select for intrapartum infections caused by other bacteria, including those resistant to antibiotics . Several advances in the development of vaccines and research on virulence factors and pathways involved in the immune response to group B streptococcus have been accomplished within the last years, including complete sequencing of the group B streptococcus genome . Development of effective vaccines and implementation of vaccination strategies will be one of the key challenges in the future for prevention of neonatal group B Streptococcus infections.

Expert Rev Anti Infect Ther, 2003 Oct, 1(3), 363 - 70
Moxifloxacin (Avelox): a novel fluoroquinolone with a broad spectrum of activity; Caeiro JP et al.; Moxifloxacin (Avelox) is a recently-developed fluoroquinolone that has a broad spectrum of antimicrobial activity, including typical respiratory pathogens, atypical and intracellular respiratory pathogens, Gram-negative pathogens and many anaerobes . This spectrum of activity makes moxifloxacin particularly suitable for the therapy of community-acquired respiratory tract infections . It also has enhanced activity against specific bacteria, such as Mycobacteria spp . and Legionella . Moxifloxacin has pharmacologic characteristics that support once-daily dosing regimens and dual routes of excretion that require little or no adjustment for renal or hepatic insufficiency . The drug has maintained an excellent safety profile based upon broad global usage, and no adverse events have occurred that were unanticipated . Streptococcus pneumoniae, which are resistant to earlier fluoroquinolones, are less likely to be resistant to moxifloxacin.

Ann Trop Paediatr, 2004 Sep, 24(3), 259 - 65
Experience with NTBC therapy in hereditary tyrosinaemia type I: an alternative to liver transplantation; Joshi SN et al.; We present the clinical data of five infants with type I (hepato-renal) tyrosinaemia on NTBC therapy . All presented initially at the local hospital in the 1st year of life with progressive abdominal distension owing to hepato-splenomegaly and with radiological evidence of liver cirrhosis, except for one child who was diagnosed during screening because of an affected sibling . Age at commencement of NTBC therapy ranged from 6 to 30 months . All infants showed remarkable improvement within 2-6 months of starting NTBC treatment, except one who died 2 months after commencement of therapy from uncontrolled liver failure, severe coagulopathy and Streptococcus pneumoniae septicaemia . NTBC treatment along with a phenylalanine- and tyrosine-restricted diet has effectively reversed most clinical manifestations of this disease . To date, none of our patients has developed hepatic carcinoma and NTBC was well tolerated without side-effects . NTBC is costly but life-saving and is an obvious alternative to more hazardous liver transplantation .

Clin Exp Allergy, 2004 Oct, 34(10), 1649 - 54
Desloratadine partially inhibits the augmented bacterial responses in the sinuses of allergic and infected mice; Kirtsreesakul V et al.; BACKGROUND: Allergic rhinitis (AR) is considered a major predisposing factor for the development of acute bacterial rhinosinusitis . How AR augments a bacterial infection is unknown . OBJECTIVE: Our purpose in this study was to test whether an H1 receptor antagonist, desloratadine, could reduce the augmented effect of an ongoing allergic reaction on acute bacterial rhinosinusitis . METHODS: Three groups of infected and ovalbumin (OVA)-sensitized mice were studied: (1) infected and allergic mice treated with desloratadine, (2) infected and allergic mice treated with placebo, and (3) infected mice . A fourth group of uninfected, non-sensitized mice served as a control for the cellular changes . BALB/c mice were sensitized by two intraperitoneal injections of OVA given 8 days apart . One day after the second injection, the mice were nasally exposed daily to 6% OVA (the groups treated with desloratadine or placebo) or phosphate-buffered saline (PBS) (the infection-only group) for 5 days . After the second OVA exposure, the mice were intranasally inoculated with Streptococcus pneumoniae . Desloratadine or placebo was given daily throughout the OVA exposure period . Nasal allergic symptoms were observed by counting of nasal rubbing and sneezing for 10 min after OVA or PBS nasal challenge . On day 5 post-infection, nasal lavage culture was done, and the inflammatory cells in the sinuses were evaluated by flow cytometry . RESULTS: Mice that were made allergic, infected, and treated with placebo showed more organisms and phagocytes than did only infect mice . They also manifested allergic nasal symptoms and eosinophil influx into the sinuses . Desloratadine treatment during allergen exposure reduced allergic symptoms and reduced sinonasal infection (P<0.05) . There tended to be less myeloid cell and neutrophil influx (P=0.09 both), but not eosinophil influx (P=0.85) compared with that in the placebo-treated group . CONCLUSION: Desloratadine treatment during nasal challenge inhibited allergic symptoms and reduced sinonasal infection, suggesting that histamine via an H1 receptor plays a role in the augmented infection in mice with an ongoing allergic reaction.

Eur J Biochem, 2004 Oct, 271(20), 4075 - 83
Cloning, expression and interaction of human T-cell receptors with the bacterial superantigen SSA; De Marzi MC et al.; Superantigens (SAgs) are a class of disease-causing and immunostimulatory proteins of bacterial or viral origin that activate a large number of T-cells through interaction with the Vbeta domain of T-cell receptors (TCRs) . In this study, recombinant TCR beta chains were constructed with human variable domains Vbeta5.2, Vbeta1 and Vbeta2.1, expressed as inclusion bodies, refolded and purified . The Streptococcus pyogenes SAg SSA-1 was cloned and expressed as a soluble periplasmic protein . SSA-1 was obtained both as a monomer and a dimer that has an intermolecular disulfide bond . We analyzed the biological activity of the recombinant SAgs by proliferation assays . The results suggest that SSA dimerization occludes the TCR interaction site . Naturally occurring SSA dimerization was also observed in supernatants of S . pyogenes isolates . An SSA mutant {SSA(C26S)} was produced to eliminate the Cys responsible for dimerization . Affinity assays using a resonant biosensor showed that both the mutant and monomeric wild type SSA have affinity for human Vbeta5.2 and Vbeta1 with Kd of 9-11 microm with a fast kass and a moderately fast kdiss . In spite of the reported stimulation of Vbeta2.1 bearing T-cells by SSA, we observed no measurable interaction.

Am J Dent, 2004 Aug, 17(4), 233 - 6
Relationship between S . mutans and the autofluorescence of carious dentin; Banerjee A et al.; PURPOSE: To investigate the relationship between the presence of S . mutans and the autofluorescent signal detected in carious dentin, using confocal laser-scanning microscopy . METHODS: Experiment 1:15 visually caries-free freshly extracted premolars were coated with varnish except for two 2 mm x 2 mm windows; five were subjected to a 15-day bacterial artificial caries system using Streptococcus mutans while 10 underwent a 7-day controlled, lactic acid (0.5 M, pH 2.7) demineralization protocol . At the end of both periods, all teeth were longitudinally sectioned and the 20 bacterial and 40 acid-induced artificial lesions were examined by confocal laser-scanning microscopy . The media containing the S . mutans was also examined for autofluorescence . Experiment 2: 20 750 microm-thick caries-free coronal dentin disks were prepared from 10 healthy premolars . Ten underwent a demineralization protocol using 0.1 M EDTA (pH 4.8) for 21 days . All 20 were finally subjected to the same artificial bacterial caries system as above for 15 days and then examined for autofluorescence using confocal laser-scanning microscopy . RESULTS: Experiment 1 results showed that acid-demineralized lesions did not generate any autofluorescence . Lesions created by the bacterial system did exhibit autofluorescence . The media with or without S . mutans did not exhibit autofluorescence . Experiment 2: bacteria-induced lesions on dentin that had previously been acid-demineralized generated a visibly stronger autofluorescence signal than those lesions grown on sound dentin . It is hypothesized that dentin demineralization during the carious process exposes more matrix to a bacteria-matrix interaction, thus generating or refining the matrix chromophore responsible for the autofluorescence signal detected in carious dentin.

J Infect Dis, 2004 Nov 1, 190(9), 1661 - 9 Epub 2004 Sep 21.
Tissue-specific contributions of pneumococcal virulence factors to pathogenesis; Orihuela CJ et al.; We assessed the ability of Streptococcus pneumoniae mutants deficient in either choline binding protein A (CbpA), pneumolysin (Pln), pyruvate oxidase (SpxB), autolysin (LytA), pneumococcal surface protein A, or neuraminidase A (NanA) to replicate in distinct anatomical sites and translocate from one site to the next . Intranasal, intratracheal, and intravenous models of disease were assessed in 4-week-old BALB/cJ mice by quantitation of bacterial titers in the relevant organs . Mice were also observed by use of real-time bioluminescent imaging (BLI) . BLI allowed visualization of the bacteria in sites not tested by sampling . All mutants were created in D39 Xen7, a fully virulent derivative of capsular type 2 strain D39 that contains an optimized luxABCDE cassette . NanA, SpxB, and, to a lesser extent, CbpA contributed to prolonged nasopharyngeal colonization, whereas CbpA and NanA contributed to the transition to the lower respiratory tract . Once lung infection was established, Pln, SpxB, and LytA contributed to bacterial replication in the lungs and translocation to the bloodstream . In the bloodstream, only Pln and LytA were required for high-titer replication, whereas CbpA was required for invasion of the cerebrospinal fluid . We conclude that transitions between body sites require virulence determinants distinct from those involved in organ-specific replication.

Mol Biotechnol, 2004 Oct, 28(2), 105 - 12
Expression of a functional single-chain Fv antibody on the surface of Streptococcus gordonii; Giomarelli B et al.; Gram-positive bacterium Streptococcus gordonii, a human oral commensal, was engineered to display a single-chain Fv (scFv) antibody fragment at the cell surface . The previously developed host-vector system allowed expression of the Guy's 13 scFv as a fusion with the streptococcal surface protein M6 . Surface expression of the 515-amino acid M6/scFv fusion protein was confirmed by Western blot analysis on cellular fractions and flow cytometric analysis . Guy's 13 scFv was derived from the Guy's 13 monoclonal antibody, which was raised against streptococcal antigen I/II (SA I/II), the major adhesin of the caries-producing bacterium Streptococcus mutans . Surface plasmon resonance was used to test binding of scFv-expressing S . gordonii to SA I/II . Whole cells of recombinant S . gordonii were found to specifically bind to immobilised SA I/II and binding was inhibited by fluid-phase SA I/II in a dose-dependent manner . Production of a functional scFv in S . gordonii is the first step towards the development of genetically engineered commensal bacteria that, by colonizing mucosal surfaces, may provide the host with sustained delivery of recombinant antibodies.

J Mol Biol, 2004 Oct 29, 343(4), 997 - 1005
Plasmin(ogen)-binding alpha-enolase from Streptococcus pneumoniae: crystal structure and evaluation of plasmin(ogen)-binding sites; Ehinger S et al.; Alpha-enolases are ubiquitous cytoplasmic, glycolytic enzymes . In pathogenic bacteria, alpha-enolase doubles as a surface-displayed plasmin(ogen)-binder supporting virulence . The plasmin(ogen)-binding site was initially traced to the two C-terminal lysine residues . More recently, an internal nine-amino acid motif comprising residues 248 to 256 was identified with this function . We report the crystal structure of alpha-enolase from Streptococcus pneumoniae at 2.0A resolution, the first structure both of a plasminogen-binding and of an octameric alpha-enolase . While the dimer is structurally similar to other alpha-enolases, the octamer places the C-terminal lysine residues in an inaccessible, inter-dimer groove restricting the C-terminal lysine residues to a role in folding and oligomerization . The nine residue plasminogen-binding motif, by contrast, is exposed on the octamer surface revealing this as the primary site of interaction between alpha-enolase and plasminogen.

Carbohydr Res, 2004 Oct 20, 339(15), 2541 - 7
Complementary exploration of the action pattern of hyaluronate lyase from Streptococcus agalactiae using capillary electrophoresis, gel-permeation chromatography and viscosimetric measurements; Kuhn AV et al.; Hyaluronic acid (HA) was treated with hyaluronate lyase (GBS HA lyase, E.C . 4.2.2.1, from Streptococcus agalactiae strain 4755), and the products have been analyzed by capillary electrophoresis (CE-UV and online CE-ESIMS), gel-permeation chromatography (GPC) and viscosimetric measurements . The resulting electropherograms showed that the enzyme produced a mixture of oligosaccharides with a 4,5-unsaturated uronic acid nonreducing terminus . More exhaustive degradation of HA led to increasing amounts of di-, tetra-, hexa-, octa- and decasaccharides . Using CE, linear relationships were found between peak area of the observed oligosaccharides and reaction time . Determination of viscosity at different stages of reaction yielded an initial rapid decrease following Michaelis-Menten theory . A reaction time-dependent change in the elution position of the HA peak due to partial digestion of HA with GBS hyaluronate lyase has been observed by GPC . These results indicated that the HA lyase under investigation is an eliminase that acts in a nonprocessive endolytic manner, as at all stages of digestion a mixture of oligosaccharides of different size were found . For GBS HA lyase from Streptococcus agalactiae strain 3502, previously published findings reported an action pattern that involves an initial random endolytic cleavage followed by rapid exolytic and processive release of unsaturated disaccharides . Our results suggest that differences between the two enzymes from distinct S . agalactiae strains (GBS strains 4755 and 3502) have to be considered.

Am J Perinatol, 2004 Oct, 21(7), 403 - 7
Low colony counts of asymptomatic group B streptococcus bacteriuria: a survey of practice patterns; Aungst M et al.; The purpose of this study was to survey expert opinion on the management of low colony counts (< 100,000 colony forming units/mL) of asymptomatic group B streptococcus (GBS) bacteriuria discovered in the first trimester . A survey was sent to the 241 senior obstetricians affiliated with each of the Obstetrics and Gynecology training programs in the United States on July 10, 2002 . Surveys received by the deadline (September 1, 2002) were included in the dataset . Eighty-five completed surveys were returned for a response rate of 35% . Seventy-seven percent reported treating low colony counts of asymptomatic GBS bacteriuria in the first trimester at the time of diagnosis, whereas 23% stated they did not treat prior to labor (margin of error 7.5% with 95% confidence) . Nine percent stated that their institution had a written protocol for the treatment of low colony counts of asymptomatic GBS bacteriuria . Two physicians indicated that they screened for asymptomatic GBS bacteriuria at 28 weeks . Currently, no generally accepted protocol for the management of low colony counts of asymptomatic GBS bacteriuria exists . This survey indicates that most of the responding senior obstetricians at United States training programs treat low colony counts of asymptomatic GBS bacteriuria in the first trimester.

N Z Med J . 2004 Aug 20;117(1200):U1023.
The prevention of early-onset neonatal group B streptococcus infection: technical report from the New Zealand GBS Consensus Working Party; Campbell N et al.; AIMS: Early-onset neonatal group B streptococcus (GBS) is the leading infectious cause of disease in newborn babies . Since intrapartum antibiotics interrupt vertical GBS transmission, this is now a largely preventable public health problem . An important first step is to develop (then implement) nationally, agreed prevention policies . METHODS: Representatives from the New Zealand College of Midwives, the Paediatric Society of New Zealand, the New Zealand Committee of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists, the Royal New Zealand College of General Practitioners, and the Homebirth Association met to review evidence that will assist in the formulation of GBS prevention policies that are most suitable for New Zealand . RESULTS: The Technical Working Group noted that (i) no strategy will prevent all cases of early-onset GBS infection, (ii) intrapartum antibiotics are associated with rare, but serious, adverse effects, (iii) concerns remain over developing antibiotic resistance, (iv) an economic analysis is required to help inform policy, (iv) reliable bedside diagnostic tests for GBS in early labour are not yet available and (iv) the most important determinant of effectiveness will be compliance with a single national prevention policy . CONCLUSIONS: As an interim measure a GBS risk-based prevention strategy is recommended . This exposes the least numbers of women and their babies to antibiotics, while virtually preventing all deaths from GBS sepsis . Continuing education of health professionals and pregnant women, auditing protocol compliance, tracking adverse events amongst pregnant women, and national surveillance of neonatal sepsis and mortality rates and antibiotic resistance are necessary for the strategy's success.

Arch Pediatr, 2004 Oct, 11(10), 1277 - 81
{Antibiotic therapy for lower tract infections in children}; Ovetchkine P; Lower respiratory tract infections in children encompass mainly bronchiolitis and community acquired pneumonia.Severity of bronchiolitis is linked to the intensity of the respiratory distress and young age . This syndrome is caused by viral infection, thus, initial antibiotherapy is not justified . In community acquired pneumonia, prognostic is dependent on the nature of the infective agent . Eventhough viruses are mainly responsible for the illness, bacterial (and particularly pneumococcal) agent cannot be ignored . Initial antibiotics must be efficient on Streptococcus pneumoniae.

Rev Argent Microbiol, 2004 Apr-Jun, 36(2), 63 - 7
{Distribution of capsular types and antimicrobial susceptibility of Streptococcus agalactiae causing infections in Argentina}; Perez J et al.; Streptococcus agalactiae is an endogenous bacterium that has emerged in the last 20 years as an etiological agent in both neonatal and perinatal infections, and in immunocompromised patients . The differentiation of the capsular polysaccharide, the presence of surface proteins c, X, R, and molecular methods allow classification in serotypes and genotypes . This identification is a useful tool for epidemiological purposes and virulence studies in this bacterium . The objective of this work was to study the serotypes and the antimicrobial susceptibility of isolates recovered from invasive diseases in different areas of Argentina . In the analyzed sample a fair predominance of Ia and III serotypes was recovered, followed by II and IV serotypes . All the isolates were found to be sensitive to penicillin . A 6% of resistance to erythromycin and a 4.5% to clindamycin were detected . In three of the isolates, constitutive MLS phenotype (resistance to macrolides, lincosamins and streptogramins) was founded, while in the remaining one, inducible MLS phenotype was detected . These results stress the importance of conducting a surveillance of the prevalent serotypes in our country with the goal of future prevention of this disease with an effective vaccine . The knowledge of the antimicrobial susceptibility profile will be also important to obtain therapeutic success in the treatment.

Clin Infect Dis, 2004 Oct 1, 39(7), 930 - 8 Epub 2004 Sep 13.
Effect of the 7-valent pneumococcal conjugate vaccine on nasopharyngeal colonization by Streptococcus pneumoniae in the first 2 years of life; Ghaffar F et al.; BACKGROUND: Studies suggest that the 7-valent pneumococcal conjugate vaccine (PCV7) reduces carriage of vaccine-type (VT) Streptococcus pneumoniae (SP) . We studied the effect of PCV7 on carriage of VT- and non-VT (NVT) SP, by studying the effect of PCV7 on nasopharyngeal (NP) colonization by VT and NVT SP during early childhood . METHODS: At 2 months of age, 278 infants were enrolled in this study . To determine carriage of SP, NP samples were obtained before each PCV7 dose, at 9 months of age, and 2-3 months after the booster dose of vaccine . RESULTS: The carriage of SP increased slightly, from 12% (95% confidence interval {CI}, 8%-16%) of subjects at 2 months of age to 18% (95% CI, 13%-23%) at 4 months of age (P<.05) . Carriage of SP remained in 24%-30% of subjects during subsequent months . Between the 12- and 18-month visits, the carriage rate of VT SP decreased significantly, from 18% (95% CI, 13%-23%) to 9% (95% CI, 5%-13%) of subjects (P=.001) . The trend of a decrease in carriage of penicillin-nonsusceptible SP, from 16% of subjects (95% CI, 11%-21%) at the 12-15-month visit to 9% (95% CI, 5%-13%) at the 15-18-month visit, was found after the booster dose of vaccine . CONCLUSION: The reduction of VT-SP colonization and replacement by NVT SP after the booster dose of vaccine suggests the possibility that widespread vaccination will result in replacement of pneumococci mainly by antibiotic-susceptible NVT SP.

J Clin Microbiol, 2004 Oct, 42(10), 4889 - 90
Culture-negative neonatal meningitis and endocarditis caused by Streptococcus agalactiae; Negre VL et al.; We describe a case of culture-negative meningitis and endocarditis caused by Streptococcus agalactiae in a 27-day-old boy . S . agalactiae was detected in cerebrospinal fluid and serum by broad-spectrum PCR amplification.

J Clin Microbiol, 2004 Oct, 42(10), 4620 - 6
Longitudinal study of transmission, diversity, and stability of Streptococcus mutans and Streptococcus sobrinus genotypes in Brazilian nursery children; Klein MI et al.; The aim of this study was to perform a follow-up evaluation of the Streptococcus mutans and Streptococcus sobrinus colonization profile of children's oral cavities, which included the pattern of vertical transmission from mother to child, genotypic diversity, and stability of the strains . The subjects were 16 mother-child pairs, who were monitored for 20 months . Samples of saliva, tongue dorsum, alveolar ridge mucosa, and dental plaque from the children were collected bimonthly . Saliva samples from the mothers were also collected . After isolation and identification, the arbitrarily primed PCR method was performed for the genotypic characterization of S . mutans (968 isolates) and S . sobrinus (111 isolates) . At the time the strains were acquired, the children harbored one to four distinct genotypes of S . mutans and only one genotype of S . sobrinus . Although S . mutans prevalence and genotypic diversity were greater than those of S . sobrinus, the presence of matching genotypes of S . mutans and S . sobrinus was similar (in 81.25 and 83.33% of mother-child pairs, respectively), suggesting vertical transmission for both species . This longitudinal study showed an increase in genotypic diversity of S . mutans in the oral cavity during the follow-up period: most of the initially acquired genotypes persisted, normally those genotypes transmitted by the mother, and some were lost during follow-up; new strains were also acquired . In conclusion, S . mutans and S . sobrinus genotypes acquired from maternal or alternative sources may show effective persistence in the oral cavity and/or transitory detection in the children's mouths, reflecting the continuous development of oral microbiota in children.

Eur J Paediatr Dent, 2004 Sep, 5(3), 131 - 5
Zinc oxide-eugenol and calcium hydroxide pulpectomies in baboon primary molars: histological responses; Cleaton-Jones P et al.; AIM: To compare histological responses to zinc oxide-eugenol (ZOE) and calcium hydroxide (CH) pulpectomies in primary molar teeth with inflamed pulps . STUDY DESIGN: This was an experimental study in 17 juvenile baboons (Papio ursinus) . METHODS: Pulpitis was induced with fresh human carious dentine or Streptococcus mutans placed into occlusal cavities in 78 primary molars; after 14 days a pulpectomy was performed on the same primary molars with the two root fillings randomly allocated . The root canal openings were then covered with IRM and the cavity filled with amalgam . After 90 days specimens were harvested and examined under the light microscope with the examiner blind to the treatment . RESULTS: Reaction frequencies in the ZOE-treated versus CH-treated teeth were: no recognisable pulp 89% and 82%, internal root resorption 0% and 1%, external root resorption 11% and 24%, presence of bacteria 5% and 18%, periapical abscesses 24% and 52% . STATISTICS: Fisher's exact probability test showed a statistically significant higher prevalence of periapical abscesses in the CH-treated group (P=0.03, relative risk 2.2) . CONCLUSIONS: ZOE pulpectomy is preferred to CH for the treatment of infected pulps in primary molars.

Rev Argent Microbiol, 2004 Apr-Jun, 36(2), 85 - 7
{Evaluation of 61 episodes of infective endocarditis in intravenous drug abusers and human immunodeficiency type-1 virus infection}; Corti ME et al.; We conducted a retrospective evaluation to determine the clinical and microbiological characteristics of 61 episodes of infective endocarditis (IE) in intravenous drug abusers (IDA), HIV seropositive patients . Forty-nine males and 6 females between 15 and 42 years of age were included in the study . All the included patients presented 61 episodes of IE . Fever and cardiac murmur were present in all episodes; 43 (70.4%) had hepatomegaly; 29 (47.5%) had splenomegaly . Thirty-eight (62.3%) presented cough (9 with hemoptysis); 25 (41%) had dyspnea, and 5 (8.2%) had jugular ingurgitation . Fundoscopy showed alterations in 3 patients (4.9%) . Bacteriological confirmation was obtained in 41 episodes (67.2%); blood cultures revealed Staphylococcus aureus in 30 cases (73.1%), Streptococcus viridans in 8 (19.5%) patients, Staphylococcus epidermidis in 1 (2.4%), Staphylococcus hominis in 1 (2.4%) and Streptococcus pneumoniae in one case (2.4%) . The tricuspid valve was involved in 51 episodes (83.6%), the aorta in 6 (9.8%), the mitral valve in 3 (4.9%) and the pulmonary valve in one (1.6%) . There was evidence of right bivalvular involvement in 2 patients (3.2%) and tricuspid and mitral involvement in another (1.6%) . Pericardial effusion was detected in 19 episodes (31.1%) . Six patients (10.9%) died during the acute episode of IE.

Rev Esp Quimioter, 2004 Jun, 17(2), 155 - 60
{Coverage of the 23-valent pneumococcal vaccine in those older than 64 years of age in the region of Castellon and Valencia, Spain}; Montaner M et al.; The different serotypes of Streptococcus pneumoniae isolated from adults aged over 64 years in the Valencia and Castellon health region of Spain from June 1999 to December 2003 were analyzed . A total of 163 strains were evaluated; 58.3% were invasive, 47.24% were from respiratory source, and 4.9% were from exudates . The greatest percentage of samples was obtained from the group of patients aged 65 to 75 years (60.7%), while the lowest percentage was obtained from the group of patients aged over 85 years (10.4%) . In the latter group, 53% of the strains were invasive and 29.4% were isolated from sputum . A total of 21 serotypes were identified, with the most common (> 3%) being: serotype 3 (22.1%); serotype 19 (12.9%); serotype 6 (12.3%); serotype 9 (8.6%); serotype 14 (10.4%); serotype 23 (8%); serotype 29 (3.7%); and serotype 18 (3.1%) . Serotype 3 was the most common serotype found in all samples, with the exception of exudate, while serotype 23 was not isolated in blood . In this population group, the coverage of the 23-valent vaccine was 88.4% . Serotypes not included in this vaccine but isolated from invasive samples were serotypes 16, 24, 29 and 35 . No changes were observed in serotype distribution over the 4-year period of the study . However, it is necessary to continue epidemiological monitoring to determine whether serotype substitution occurs.

Cell Microbiol, 2004 Nov, 6(11), 1085 - 96
Candida albicans and Streptococcus salivarius modulate IL-6, IL-8, and TNF-alpha expression and secretion by engineered human oral mucosa cells; Mostefaoui Y et al.; We investigated the involvement of oral epithelial cells via two cytokines (IL-6 and TNF-alpha) and one chemokine (IL-8) in local defences against live yeast (Candida albicans) and bacteria (Streptococcus salivarius) using an engineered human oral mucosa model . We report that the yeast changed from the blastospore to the hyphal form and induced significant tissue disorganization at later contact periods (24 and 48 h) compared to the bacteria . However, this effect did not reduce the viability or total number of epithelial cells . Gene activation analyses revealed that IL-6, IL-8 and TNF-alpha mRNA levels rose in tissues in contact with live C . albicans or S . salivarius . Gene activation was followed by an upregulation of protein secretion . IL-6 levels were higher after contact with C . albicans than with S . salivarius . IL-8 levels after contact with S . salivarius were higher than with C . albicans . Our study suggests that S . salivarius is more efficient at inducing proinflammatory mediator release than C . albicans . These results provide additional evidence for the contribution of oral epithelial cells to the inflammatory response against fungi and bacteria.

Med J Malaysia, 2004 May, 59 Suppl B, 59 - 60
Amplifying the manganese scavenging potential of Streptococcus zooepidemicus to reactive oxygen species during production of hyaluronic acid; Mashitah MD et al.; Streptococcus zooepidemicus (SZ) is an aerotolerant bacteria and its ability to survive under reactive oxidant challenge raises the question of the existence of a defense system . Thus growth, hyaluronic acid (HA) and hydrogen peroxide (H2O2) production by SZ in the presence of increasing concentration of Mn2+ were studied . The results suggested that the tested strain supported growth and HA production in cultures treated with 1 and 10 mM of Mn2+ regardless of H2O2 presence in the medium . This showed that SZ have acquired elaborate defense mechanisms to scavenge oxygen toxicity and thus protect cells from direct and indirect effect of this radical . In contrast, cells treated with 25 mM Mn2+ were sensitive, in which, the HA production was reduced considerably . Thus showing that the oxygen scavenger systems of the cells may be fully saturated at this concentration.

Nippon Yakurigaku Zasshi, 2004 Oct, 124(4), 271 - 83
{Anti-allergic action effect of Pseudolarix amabilis Rehd . extract and its efficacy on atopic dermatitis}; Hirasawa Y et al.; Pseudolarix amabilis Rehd . extract was examined in vitro for antibacterial effects, anti-inflammatory effects, and inhibitory effects on histamine release . Pseudolarix amabilis Rehd . extract was also examined for efficacy on dermatitis in atopic dermatitis model mice (NC mice) and effects on keratinous moisture level and transepidermal water loss in miniature pigs . Pseudolarix amabilis Rehd . extract had antibacterial effects on Staphylococcus aureus, Candida albicans, and Streptococcus pyogenes; however this antibacterial effect varied with the temperature at which and conditions under which Pseudolarix amabilis Rehd . was extracted . Pseudolarix amabilis Rehd . extract at the final concentration of 2 mg/mL significantly inhibited the hyaluronidase activity; and at 0.005, 0.05, and 0.5 mg/mL, it also significantly inhibited the histamine release . In the mice in which atopic dermatitis had been induced, 28-day administration of Pseudolarix amabilis Rehd . extract at 4 and 400 mg/mL significantly inhibited aggravation of dermatitis without having effects on body weight . In the dorsal skin of miniature pigs, Pseudolarix amabilis Rehd . extract at 4 and 400 mg/mL significantly increased keratinous moisture level with the increase in the number of dosing days, and caused no changes in transepidermal water loss . From the above results, it is clear that Pseudolarix amabilis Rehd . extract inhibits both proliferation of bacteria and inflammation caused by antigens . Furthermore, it is suggested that Pseudolarix amabilis Rehd . extract will serve as a medicinal drug which effectively moistens the skin and prevents and heals dermatitis.

Appl Environ Microbiol, 2004 Oct, 70(10), 6047 - 52
Galactose metabolism by Streptococcus mutans; Abranches J et al.; The galK gene, encoding galactokinase of the Leloir pathway, was insertionally inactivated in Streptococcus mutans UA159 . The galK knockout strain displayed only marginal growth on galactose, but growth on glucose or lactose was not affected . In strain UA159, the sugar phosphotransferase system (PTS) for lactose and the PTS for galactose were induced by growth in lactose and galactose, although galactose PTS activity was very low, suggesting that S . mutans does not have a galactose-specific PTS and that the lactose PTS may transport galactose, albeit poorly . To determine if the galactose growth defect of the galK mutant could be overcome by enhancing lactose PTS activity, the gene encoding a putative repressor of the operon for lactose PTS and phospho-beta-galactosidase, lacR, was insertionally inactivated . A galK and lacR mutant still could not grow on galactose, although the strain had constitutively elevated lactose PTS activity . The glucose PTS activity of lacR mutants grown in glucose was lower than in the wild-type strain, revealing an influence of LacR or the lactose PTS on the regulation of the glucose PTS . Mutation of the lacA gene of the tagatose pathway caused impaired growth in lactose and galactose, suggesting that galactose can only be efficiently utilized when both the Leloir and tagatose pathways are functional . A mutation of the permease in the multiple sugar metabolism operon did not affect growth on galactose . Thus, the galactose permease of S . mutans is not present in the gal, lac, or msm operons.

J Biol Chem, 2004 Dec 10, 279(50), 52789 - 96 Epub 2004 Dec 10.
Insight of host immune evasion mediated by two variants of group a Streptococcus Mac protein; Agniswamy J et al.; Group A Streptococcus has evolved numerous mechanisms to evade the host immune system to survive, disseminate, and cause disease . Recently a secreted protein named Mac-1 was identified and shown to enhance survival of the pathogen . A new variant of Mac-1 (designated Mac-2) also was recently described and shown to differ from Mac-1 by approximately 50% amino acid sequence divergence in the middle one-third of the molecule . To gain new information about the role of Mac-1 and Mac-2 in host-pathogen interactions, solution binding experiments were performed using surface plasmon resonance and purified Mac proteins . Mac-1 bound the same lower hinge region of human IgG as Fc receptors with 2.5 microM affinity, which lead to proteolytic cleavage of the antibody . Similar Km (6.8-18.9 microM) and kcat (0.02-0.13 s(-1)) values of the Mac-1 endopeptidase activity were obtained for IgG1, IgG2, IgG3, and IgG4 . Mac-2 variant, in contrast, bound human IgG poorly (KD = 16 mM) and had weak endopeptidase activity against IgG . Instead, Mac-2 bound FcgammaRII and FcgammaRIII with 5 and 75 microM affinity, respectively . This binding competitively blocked IgG from recognition by Fc receptors . Taken together, Mac proteins block immunoglobulin recognition by Fc receptors and degrade immunoglobulins, thereby enhancing survival of the pathogen through the inhibition of phagocytosis, endocytosis of IgG-opsonized particles, and antibody-dependent cell-mediated cytotoxicity . Consequently, these proteins may be potential therapeutic targets.

Pathol Biol (Paris), 2004 Oct, 52(8), 489 - 92
{Emergence of macrolide resistant Streptococcus pyogenes strains in pediatric patients in France}; Mariani-Kurkdjian P et al.; A total of 206 recent throat isolates of Streptococcus pyogenes collected between 2002 and 2004 from children were tested for their susceptibility to penicillin, amoxycillin, erythromycin, clarythromycin and clindamycin . The erythromycin resistant isolates were further studied for their genetic mechanism of resistance by means of PCR . In all, 14.5% of the strains were erythromycin resistant and 13.5 and 1% expressed the constitutive MLS(B) and M resistance phenotypes and harbored the ermB and mef A genes respectively.

Pathol Biol (Paris), 2004 Oct, 52(8), 438 - 43
{Rapid antigen detection tests for diagnosis of group A streptococcal pharyngitis: comparative evaluation of sensitivity and practicability of 16 in vitro diagnostics medical devices performed in July 2002 by the French health products safety agency (Afssaps) as part of its market control mission}; Charlier-Bret N et al.; Within the scope of its health products control mission, the French Health Products Safety Agency (Afssaps) collaborating with two expert's sites, has assessed the 16 tests available on the French market in 2002 for rapid diagnosis of the Streptococcus A tonsillitis . The purpose of this study was to verify the reliability and rapidity of these tests and to give some information to the users about their analytical criteria and practicability characteristics . The analytical study has been performed on a same panel of four reference strains of Streptococcus pyogenes dilutions to determine the limit of detection of all the reagents in the same condition of methodology . The limit of detection has been calculated with the results expressed in colony forming unit by ml (CFU/ml) . The practicability study has permitted to analyze the quality of the presentation, the easiness of the final reading and of performing tests . A score has been established for each rapid test . A classification of the analytical sensitivity (limit of detection) and practicability (score) of these 16 devices has been established . The limit of detection of the reagents giving the best results allows the detection of the lowest bacterial concentration of the panel which is 10(5) CFU/ml . Regarding practicability, the results suggest that, the immunochromatographic strip methods have the best score in a view with the use by a non medical laboratory.

Nutr J . 2004 Oct 05;3(1):18.
Effect of smoking on vitamin A, vitamin E, and other trace elements in patients with cardiovascular disease in Bangladesh: a cross-sectional study; Bashar SK et al.; BACKGROUND: Data regarding the impact of cigarette smoking on trace elements are scarce and inconsistent . In this study, we evaluated the effect of smoking on serum concentrations of trace elements among adult males with heart disease . METHODS: This cross-sectional study included 100 adults hospitalized with heart disease in Bangladesh . The major variables of interest included mean serum concentrations of trace elements and proportion of subjects with bacterial growth on throat swab culture . RESULTS: Smokers had significantly lower serum concentrations of retinol, alpha-tocopherol, selenium, and zinc and increased concentrations of copper . Throat swab cultures were more often positive for Streptococcus beta-hemolyticus in smokers than controls . CONCLUSIONS: Smoking decreases serum concentrations of trace elements . Smoking control programs are needed in Bangladesh to improve health and nutrition of the people who are already nutritionally deficient.

Gastroenterol Hepatol, 2004 Aug-Sep, 27(7), 393 - 6
{Evaluation of Helicobacter pylori susceptibility to rifaximin}; Quesada M et al.; INTRODUCTION: Helicobacter pylori infection affects more than half the world's population . It is a major cause of chronic gastritis and there is a strong association with peptic ulceration and gastric adenocarcinoma . Rifaximin is a new nonabsorbable broad-spectrum antimicrobial agent that reaches high concentrations in the gastrointestinal tract . AIM: To evaluate the in vitro activity of rifaximin against H . pylori isolates . METHODS: Thirty-one H . pylori strains were analyzed by the agar dilution method . Clarithromycin was used as the control antibiotic . Staphylococcus aureus and Streptococcus pneumoniae were used as quality control strains . Plates were read at days 4 and 7 of incubation . The MIC50 and MIC90 of each antibiotic were calculated . Strains with a clarithromycin MIC of > 1 microg/ml were considered resistant . RESULTS: The MIC50 of clarithromycin at days 4 and 7 was 0.125 microg/ml and the MIC90 at days 4 and 7 ranged from 8 to 16 microg/ml, respectively . The MIC50 of rifaximin at days 4 and 7 ranged from 1 to 2 microg/ml, respectively, and the MIC90 was 4 microg/ml at both days 4 and 7 . Twenty percent of H . pylori strains were resistant to clarithromycin . All clarithromycin-resistant strains were inhibited at a maximal rifaximin concentration of 4 microg/ml . CONCLUSION: These results indicate that this new antibiotic may be useful for eradication of H . pylori infection . Because rifaximin is active against H . pylori strains resistant to clarithromycin, it could be useful in combination with this drug or in the treatment of therapeutic failure.

Sichuan Da Xue Xue Bao Yi Xue Ban, 2004 Sep, 35(5), 687 - 9
{The effects of natural medicine on adherence of Streptococcus mutans to salivary acquired pellicle}; Xiao Y et al.; OBJECTIVE: To investigate the effects of 5 kinds of natural medicine such as Radix et Rhizoma Rhei on the adherence of Streptococcus mutans to salivary acquired pellicle, and to screen effective natural medicines for the prevention of caries . METHODS: The in vitro model of experimental pellicle was saliva-coated hydroxyapatites (S-HA) . Streptococcus mutans and S-HA were treated with natural medicines respectively, and then the adherence of bacteria to S-HA was tested . RESULTS: Radix et Rhizoma Rhei, Semen Arecae and Rhizoma Liguistici Chuanxiong could decrease the attachment of Streptococcus mutans to S-HA, and Semen Arecae was the most effective one . Radix Angelicae Dahuricae had no remarkable effect, and Catechu inhibited the adherence only after the bacteria being under treatment . CONCLUSION: Radix et Rhizoma Rhei, Semen Arecae, Rhizoma Liquistici Chuanxiong and Catechu could effectively inhibit the adherence of Streptococcus mutans to salivary acquired pellicle, but the effect of Radix Angelicae Dahuricae on the adherence is un-noticeable.

Infect Dis Obstet Gynecol, 2004, 12(1), 27 - 30
Perimenopausal pneumococcal tubo-ovarian abscess--a case report and review; Seshadri S et al.; BACKGROUND: Genital tract infections in females secondary to Streptococcus pneumoniae (pneumococcus) are unusual . Tubo-ovarian abscess resulting from such an infection is a rare occurrence and diagnosis is not always easy . This report demonstrates the problems of recognizing this condition and summarizes the pathomechanism, investigations leading to a diagnosis and the subsequent management . CASE: A rare case of a tubo-ovarian abscess caused by pneumococcus, occurring in a previously healthy 48-year-old woman, is presented . The tubo-ovarian abscess may have developed insidiously and probably had an acute exacerbation prior to presentation . CONCLUSION: This case is unusual in that there were no identifiable initiating events for the source of the pneumococcal infection . Early recognition of a tubo-ovarian abscess is important in order to prevent the associated morbidity and mortality . This condition has the propensity to mimic a neoplasm.

Infect Dis Obstet Gynecol, 2004, 12(1), 1 - 8
Antibiotic resistance patterns of group B streptococcal clinical isolates; Simoes JA et al.; OBJECTIVES: To determine the in vitro resistance of group B streptococcus (GBS) to 12 antibiotics . To determine if there has been any decrease in sensitivity to the penicillins or other antibiotics currently used for GBS chemoprophylaxis in pregnant women . Find suitable alternative antibiotics to penicillin . Find an antibiotic that will have minimal selective pressure for resistance among the endogenous resident vaginal microflora . METHODS: The antibiotic susceptibility profiles of 52 clinical isolates of GBS were evaluated to 12 antibiotics: ampicillin, azithromycin, cefamandole, cefazolin, ceftriaxone, ciprofloxacin, clindamycin, erythromycin, nitrofurantoin, ofloxacin, penicillin and vancomycin . Antibiotic sensitivities were determined using disk diffusion and microdilution methods according to the guidelines of the National Committee for Clinical Laboratory Standards (NCCLS) . RESULTS: All isolates were sensitive to vancomycin, ofloxacin, ampicillin, ciprofloxacin, nitrofurantoin and penicillin . However, the following number of clinical isolates exhibited intermediate or decreased sensitivity, nine (17%) to ampicillin, eight (15%) to penicillin, 14 (32%) to ciprofloxacin and one (2%) to nitrofurantoin . Thirty-one percent of the isolates were resistant to azithromycin and ceftriaxone, 19% to clindamycin, 15% to cefazolin and 13% to cefamandole . Eighteen (35%) of the clinical isolates tested were resistant to 6 of the 12 antibiotics tested . CONCLUSIONS: The relatively high rates of resistance for 6 of the 12 antibiotics tested suggest that for women allergic to penicillin and colonized with GBS, antibiotic sensitivities to their isolates should be determined . The antibiotic selected for intrapartum chemoprophylaxis should be guided by the organism's antibiotic sensitivity pattern . Patients with GBS bacteriuria should be treated with nitrofurantoin.

Reprod Nutr Dev, 2004 May-Jun, 44(3), 195 - 206
Protozoa involved in butyric rather than lactic fermentative pattern during latent acidosis in sheep; Brossard L et al.; We used six ruminally cannulated Texel wethers to study the relative role of protozoa and lactate-metabolizing bacteria in ruminal fermentative patterns during an induced latent acidosis . The sheep were fed an alfalfa hay diet (H) and latent acidosis was induced, following a short transition period of one week, with a grain-rich acidotic diet (W, 60% wheat + 40% alfalfa hay) . Ruminal pH, ruminal volatile fatty acids (VFA), lactate and NH3 concentrations, protozoa and lactate-utilizing bacterial counts, the relative proportions of three main bacteria implicated in lactate metabolism (a lactate-producing species, Streptococcus bovis, and two lactate-utilizing species, Selenomonas ruminantium, and Megasphaera elsdenii) using specific 16S-rRNA-targeting oligonucleotide probes, and lactate dehydrogenase (LDH) activity were determined for both diets . The pH parameters (mean, minimum, maximum, time and area under pH 6.0 and 5.5) measured with the W diet were indicative of a latent (i.e., subacute and maintained) acidosis . However, a butyric rather than lactic latent acidosis was observed in this study . Total ruminal lactate concentration remained at low levels with the acidotic diet (< 4 mmol x L(-1)), but changes were observed in VFA composition, which was oriented towards butyrate at the expense of acetate (P < 0.05), while propionate remained constant . In agreement with the low ruminal lactate concentration, no changes in the proportion of S . bovis 16S-rRNA were observed . The lactate-metabolizing bacterial population also remained fairly constant in number, proportion and activity . The increase in butyrate concentration was accompanied by a proliferation of entodiniomorphs (P < 0.01) . These results suggest that the protozoa limited lactate accumulation and possibly also the decrease in pH during latent acidosis . Experiments with defaunated and faunated sheep could provide further evidence of the role of protozoa in the development of rumen latent acidosis.

Ann Emerg Med, 2004 Oct, 44(4), 386 - 92
Pneumococcal vaccination in the emergency department: an assessment of need; Rudis MI et al.; STUDY OBJECTIVES: Immunization against Streptococcus pneumoniae with the 23-valent pneumococcal polysaccharide vaccine has been shown to be cost-effective for prevention of invasive pneumococcal disease . Yet 23-valent pneumococcal polysaccharide vaccine is widely underused, particularly among ethnic minorities . The objectives of this survey are to determine the rate of 23-valent pneumococcal polysaccharide vaccine vaccination among all adult patients presenting to the emergency department (ED) of a county-based, urban, tertiary care medical center; the willingness of patients to receive 23-valent pneumococcal polysaccharide vaccine; and reasons for nonvaccination . METHODS: A quality assurance survey was performed in the ED during 3 days in September 2002 . A survey was developed to determine 23-valent pneumococcal polysaccharide vaccine vaccination rates and eligibility according to indications and contraindications established by the Centers for Disease Control and Prevention (CDC) . Descriptive statistics were performed to quantify the proportion of patients who were immunized, eligible, and willing to receive 23-valent pneumococcal polysaccharide vaccine and reasons for nonvaccination . RESULTS: A total of 250 patients of 1,535 registered in the ED were surveyed during the 3-day period . Only 48 (19%) had a primary care provider . The majority of patients were Hispanic (73%) . Only 22 (9%) patients had received the vaccine . A total of 66 (26%) patients fit the CDC eligibility criteria for 23-valent pneumococcal polysaccharide vaccine, and 59 (89%) of these patients were willing to receive the vaccine during their ED visit . Most patients (79%) were eligible to receive 23-valent pneumococcal polysaccharide vaccine due to their comorbid illnesses . CONCLUSION: In the ED of our county-based urban medical center, 26% of patients were eligible for 23-valent pneumococcal polysaccharide vaccine; the majority of patients were Hispanic, unaware of the vaccine's existence, and willing to receive it during their ED visit . These data underscore a large unmet public health need among ethnic minorities in the ED.

Microb Pathog, 2004 Oct, 37(4), 193 - 204
Alteration of gene expression in human middle ear epithelial cells induced by influenza A virus and its implication for the pathogenesis of otitis media; Tong HH et al.; Influenza A virus infection plays a significant role in the pathogenesis of Streptococcus pneumoniae-induced acute otitis media in children . An understanding of how influenza A virus modulates host cellular responses is critically important in efforts to explore the molecular mechanisms of this synergism . We used microarray technology to characterize the mRNA expression profile in human middle ear epithelial cells induced by influenza A virus . Alterations of mRNA expression in 142 out of approximately 12,600 genes were observed at 24h after virus infection . Of these 142 genes with altered expression, interferon inducible genes, chemokine and cytokine genes, pro- and antiapoptotic genes, signal transduction and transcription factors, cellular immune response, cell cycle and metabolism genes were the most prominent . Our results reveal several previously unknown alterations of host gene expression induced by influenza A virus which may provide new targets for further analysis of its role in this particular host-pathogen interaction.

J Vet Med B Infect Dis Vet Public Health, 2004 Aug, 51(6), 272 - 7
Immunogenicity of murein-associated proteins from temperature-stressed Streptococcus suis cultures; Benga L et al.; We compared immunogenicity in pigs of whole cell lysate proteins (WCP) with murein-associated proteins (MAP) obtained from a virulent serotype 2 strain of Streptococcus (S.) suis grown at 32 or 42 degrees C . Protein fractions were tested for their ability to induce antibodies in 3-week-old piglets by enzyme-linked immunosorbent assay and Western blot analysis . We found a significant increase in the antibody levels in all sera irrespective of the preparation used for immunization . However, alpha-WCP sera showed higher reactivities than alpha-MAP sera, and piglets immunized with 32 degrees C preparations (alpha-32 sera) showed higher responses than those immunized with 42 degrees C preparations (alpha-42 sera) . Western blot analysis revealed that alpha-WCP sera in part reacted with different proteins when compared with alpha-MAP sera . Furthermore, some proteins were only detected by alpha-32 but not by alpha-42 sera . In conclusion, the results demonstrate the immunogenicity of cell wall MAP of S . suis, and highlight the importance of considering growth conditions in the preparation of subunit vaccines.

Mol Microbiol, 2004 Oct, 54(1), 172 - 83
Identification of ComW as a new component in the regulation of genetic transformation in Streptococcus pneumoniae; Luo P et al.; Regulation of competence for genetic transformation in Streptococcus pneumoniae depends on a quorum-sensing system, genes involved in DNA uptake and recombination and a link between these two gene sets . The alternative sigma factor ComX provides this link . ComE, the response regulator of the quorum-sensing system, is required for expression of ComX and other early genes . However, an unknown ComE-dependent regulator is also required for competence when comX is expressed under control of the raffinose-responsive promoter of the aga operon . The gene comW (SP0018) is required for a high level of competence and is regulated by the quorum-sensing system, but its function is unknown . To explore its role further, comW was cloned into the multicopy plasmid pMSP3535, under the control of a nisin-inducible promoter (P(N)), and transformed into pneumococcal strains containing a raffinose-inducible comX gene (P(R)::comX) . Further introduction of a comE deletion blocked the endogenous CSP signal transduction pathway . In the resulting strain, competence was independent of CSP but depended on treatment with both nisin and raffinose, showing that coexpression of comW and comX complemented the comE deficiency . ComX protein accumulation and expression of a late competence gene in the above strain support the conclusion that ComW is a new positive factor involved in competence regulation.

Mol Microbiol, 2004 Oct, 54(1), 159 - 71
Phase variable desialylation of host proteins that bind to Streptococcus pneumoniae in vivo and protect the airway; King SJ et al.; Most clinical isolates of Streptococcus pneumoniae consist of heterogeneous populations of at least two colony phenotypes, opaque and transparent, selected for in the bloodstream and nasopharynx, respectively . Microarray analysis revealed 24 orfs that demonstrated differences in expression greater than twofold between variants of independent strains . Twenty-one of these showed increased expression in the transparent variants, including 11 predicted to be involved in sugar metabolism . A single genomic region contains seven of these loci including the gene that encodes the neuraminidase, NanA . In contrast to previous studies, there was no contribution of NanA to adherence of S . pneumoniae to epithelial cells or colonization in an animal model . However, we observed NanA-dependent desialylation of human airway components that bind to the organism and may mediate bacterial clearance . Targets of desialylation included human lactoferrin, secretory component, and IgA2 that were shown to be present on the surface of the pneumococcus in vivo during pneumococcal pneumonia . The efficiency of desialylation was increased in the transparent variants and enhanced for host proteins binding to the surface of S . pneumoniae . Because deglycosylation affects the function of many host proteins, NanA may contribute to a protease-independent mechanism to modify bound targets and facilitate enhanced survival of the bacterium.

Mol Microbiol, 2004 Oct, 54(1), 23 - 31
Molecular pathogenesis of neonatal group B streptococcal infection: no longer in its infancy; Doran KS et al.; The process of human infection by group B Streptococcus (GBS) is complex and multifactorial . While this bacterium has adapted well to asymptomatic colonization of adult humans, it remains a potentially devastating pathogen to susceptible infants . Advances in molecular techniques and refinement of in vitro and in vivo model systems have elucidated key elements of the pathogenic process, from initial attachment to the maternal vaginal epithelium to penetration of the newborn blood-brain barrier . Sequencing of two complete GBS genomes has provided additional context for interpretation of experimental data and comparison to other well-studied pathogens . Here we review recent discoveries regarding GBS virulence mechanisms, many of which are revealed or magnified by the unique circumstances of the birthing process and the deficiencies of neonatal immune defence . Appreciation of the formidable array of GBS virulence factors underscores why this bacterium remains at the forefront of neonatal pathogens.

Lakartidningen, 2004 Aug 26, 101(35), 2642 - 4
{High-dose immunoglobulin--life-saving in invasive group A streptococcal infection . Report of eleven cases with only one fatality}; Arnholm B et al.; Invasive group A streptococcal infection is an uncommon but severe disease . Bloodcultures usually yield growth of Streptococcus pyogenes and the bacteria may also be isolated from sterile sites e.g . muscle or pleura . The most serious manifestation is Streptococcal Toxic Shock Syndrome (STSS) with or without necrotizing fasciitis (NF) . This condition may occur in about a fifth of the cases with a very high case-fatality rate . Preclinical data and case reports suggest that the fatality rate can be reduced by treatment of high-dose intravenous immunoglobulin . A European placebo-controlled clinical trial with immunoglobulin has been conducted but was prematurely terminated due to difficulties in patient recruitment . In our clinic we have during the last 3.5 years seen 41 patients with invasive group A streptococcal infection and 11 of these have received high-dose immunoglobulin . The indication for that treatment has been hypotension and multiorgan failure . All 11 patients but one fullfilled the criteria for STSS and 5 had NF . Most of the patients were treated with a single dose intravenous infusion of 50 g immunoglobulin . All patients were treated with both benzylpenicillin and clindamycin . Ten patients were fully recovered--case-fatality rate 9 percent . We suggest that patients with invasive group A streptococcal infections who develop STSS with or without NF should be treated with high-dose intravenous immunoglobulin.

Drugs, 2004, 64(20), 2347 - 77
Moxifloxacin: a review of its use in the management of bacterial infections; Keating GM et al.; Moxifloxacin (Avelox) is a fluoroquinolone antibacterial with a methoxy group in the C-8 position and a bulky C-7 side chain . Moxifloxacin is approved for use in the treatment of acute exacerbations of chronic bronchitis (AECB), community-acquired pneumonia (CAP), acute bacterial sinusitis and uncomplicated skin and skin structure infections (approved indications may differ between countries) . Moxifloxacin has a broad spectrum of antibacterial activity, including activity against penicillin-resistant Streptococcus pneumoniae . It achieves good tissue penetration and has a convenient once-daily administration schedule, as well as being available in both intravenous and oral formulations in some markets . Moxifloxacin has good efficacy in the treatment of patients with AECB, CAP, acute bacterial sinusitis and uncomplicated skin and skin structure infections, and is generally well tolerated . Thus, moxifloxacin is an important option in the treatment of bacterial infections .

J Dairy Sci, 2004 Jun, 87(6), 1727 - 31
Influence of prepartum pirlimycin hydrochloride or penicillin-novobiocin therapy on mastitis in heifers during early lactation; Oliver SP et al.; A study was conducted in 2 dairy research herds to determine whether prepartum therapy of heifer mammary glands with penicillin-novobiocin or pirlimycin hydrochloride was effective for reducing the percentage of heifers and mammary quarters infected with mastitis pathogens during early lactation . Almost 96% of Jersey heifers (67 of 70) and 71.3% of quarters (199 of 279) were infected 14 d before expected calving . Of the quarters infected at 14 d before expected parturition, 75% (54 of 72) were uninfected following treatment with penicillin-novobiocin; 87% (61 of 70) were uninfected following treatment with pirlimycin, and 56% (32 of 57) were uninfected in the untreated negative control group . The majority of intramammary infections in Jersey heifers were due to coagulase-negative staphylococci (61%), Streptococcus species, primarily Streptococcus uberis (19%), and Staphylococcus aureus (8%) . Almost 73% of Holstein heifers (40 of 55) and 34.3% of mammary quarters (73 of 213) were infected 14 d before expected calving . Of the quarters infected at 14 d before expected parturition, 76% (19 of 25) were uninfected following treatment with penicillin-novobiocin; 59% (17 of 29) were uninfected following treatment with pirlimycin, and 26% (5 of 19) were uninfected in the untreated negative control group . The majority of intramammary infections in Holstein heifers were due to coagulase-negative staphylococci (44%) and Staph . aureus (30%) . In both herds, the bacteriological cure rate was significantly higher in heifer mammary glands treated with penicillin-novobiocin or pirlimycin hydrochloride than in untreated controls . Prepartum therapy of heifer mammary glands with penicillin-novobiocin or pirlimycin hydrochloride significantly reduced the percentage of heifers and quarters infected with mastitis pathogens during early lactation.

Chemotherapy, 2004 Oct, 50(4), 196 - 201 Epub 2004 Sep 23.
Activity of nadifloxacin (OPC-7251) and seven other antimicrobial agents against aerobic and anaerobic Gram-positive bacteria isolated from bacterial skin infections; Nenoff P et al.; BACKGROUND AND METHODS: The in vitro activity of nadifloxacin (OPC-7251), a novel topical fluoroquinolone, was assessed and compared with those of ofloxacin, oxacillin, flucloxacillin, cefotiam, erythromycin, clindamycin, and gentamicin against 144 Gram-positive bacteria: 28 Staphylococcus aureus, 10 Streptococcus spp., 68 coagulase-negative staphylococci (CNS), 36 Propionibacterium acnes, and 2 Propionibacterium granulosum strains . All strains originated from bacterial-infected skin disease and were isolated from patients with impetigo, secondary infected wounds, folliculitis and sycosis vulgaris, and impetiginized dermatitis . In vitro susceptibility of all clinical isolates was tested by agar dilution procedure and minimum inhibitory concentrations (MICs) were determined . RESULTS: Nadifloxacin was active against all aerobic and anaerobic isolates . MIC(90) (MIC at which 90% of the isolates are inhibited) was 0.1 microg/ml for S . aureus, 0.78 microg/ml for both Streptococcus spp . and CNS, and 0.39 microg/ml for Propionibacterium spp . On the other hand, resistant strains with MICs exceeding 12.5 mug/ml were found in tests with the other antibiotics . For both CNS and Propionibacterium acnes, MIC(90) values > or =100 microg/ml were demonstrated for erythromycin . Ofloxacin, cefotiam, erythromycin, clindamycin and gentamicin exhibited MIC(90) values < or =1 microg/ml for some bacterial species tested . Both oxacillin and flucloxacillin were active against all investigated bacterial species with MIC(90) values < or =1 microg/ml . CONCLUSION: In summary, nadifloxacin, a topical fluoroquinolone, was found to be highly active against aerobic and anaerobic bacteria isolated from patients with infected skin disease, and seems to be a new alternative for topical antibiotic treatment in bacterial skin infections.

Int Immunol, 2004 Nov, 16(11), 1605 - 11 Epub 2004 Sep 27.
LPS-binding protein-deficient mice have an impaired defense against Gram-negative but not Gram-positive pneumonia; Branger J et al.; LPS-binding protein (LBP) can facilitate the transfer of cell wall components of both Gram-negative bacteria (LPS) and Gram-positive bacteria (lipoteichoic acid) to inflammatory cells . Although LBP is predominantly produced in the liver, recent studies have indicated that this protein is also synthesized locally in the lung by epithelial cells . To determine the role of LBP in the immune response to pneumonia, LBP gene-deficient (-/-) and normal wild-type (WT) mice were intra-nasally infected with either Streptococcus pneumoniae or Klebsiella pneumoniae, common Gram-positive and Gram-negative pathogens, respectively . Pneumococcal pneumonia was associated with a 7-fold rise in LBP concentrations in bronchoalveolar lavage fluid of WT mice; LBP-/- mice infected with S . pneumoniae showed a similar survival and a similar bacterial burden in their lungs 48 h post-infection . In Klebsiella pneumonia, however, LBP-/- mice demonstrated a diminished survival together with an enhanced bacterial outgrowth in their lungs . These data suggest that LBP is important for a protective immune response in Klebsiella pneumonia, but does not contribute to an effective host response in pneumococcal pneumonia.

Anal Biochem, 2004 Oct 15, 333(2), 296 - 302
Detection of cariogenic bacteria genes by a combination of allele-specific polymerase chain reactions and a novel bioluminescent pyrophosphate assay; Arakawa H et al.; We developed a novel bioluminescent assay for detection of pyrophosphate in polymerase chain reaction (PCR) product . The principle of this method is as follows: pyrophosphate released by PCR is converted to adenosine 5'-triphosphate (ATP) by pyruvate phosphate dikinase in the presence of the substrate pyruvate phosphate and the coenzyme adenosine 5'-monophosphate; subsequently, ATP concentration is determined by firefly luciferase reaction . The detection limit of pyrophosphate is 1.56 x 10(-15)mol/assay . Additionally, luminescent intensity reached a maximum at approximately 100 s and remained elevated beyond 10 min . This approach is applicable to the detection of cariogenic bacteria in dental plaque . Thus, the allele-specific PCR products of Streptococcus mutans and Streptococcus sobrinus developed in this study were measured via the proposed bioluminescent assay . This protocol, which does not require expensive equipment, can be utilized to rapidly monitor cariogenic bacteria in dental plaque.

Colloids Surf B Biointerfaces, 2004 Aug 15, 37(1-2), 53 - 60
Path-dependency of the interaction between coaggregating and between non-coaggregating oral bacterial pairs--a thermodynamic approach; Postollec F et al.; Coaggregation, i.e . specific recognition between bacteria from different species, is a well-described phenomenon in the human oral cavity but remains physically poorly understood . With our study we aimed at elucidating some aspects of the mechanism of the coaggregation between the oral bacteria Streptococcus oralis J22 and Actinomyces naeslundii 147, in particular with respect to the driving force for coaggregation and its pathway-dependency . To that end, the macroscopic turbidity of the bacterial suspension, the morphology of the coaggregates, binding isotherms and heats of interaction were compared between the above-mentioned coaggregating bacterial pair and a non-coaggregating pair, Streptococcus sanguis PK1889 and A . naeslundii 147 . The coaggregating pair forms large aggregates, which rapidly sediment from the suspension while the non-coaggregating pair forms only very small coaggregates that remain homogeneously suspended . Coaggregation is further characterized by a high affinity between the partner cells that bind to each other in a strong cooperative mode . The interactions between both pairs occur under the release of heat and are thus enthalpically favorable . More heat is released for the coaggregating than for the non-coaggregating pair . Adding the coaggregating bacteria in steps to each other leads to saturation of enthalpically favorable binding sites . This is observed when the streptococcus is added to the actinomyces as well as when the addition is done the other way around . It is concluded that the cooperativity of the coaggregation process is based on an increase of entropy . It is furthermore shown that the density of the coaggregates as well as the heat effect of formation of these coaggregates depend on the number of steps in which the partner cells are added to each other . Adding S . oralis J22 in three steps to A . naeslundii 147 results in the formation of denser coaggregates under the release of less heat, as compared to that of addition in one step . These differences point to a larger entropy increase when in a step-wise mixing the coaggregating bacteria are allowed to form more densely-packed coaggregates.

Rev Med Chil, 2004 Feb, 132(2), 219 - 22
{Acute suppurative thyroiditis . Report of a pediatric case}; Giadrosich V et al.; Acute suppurative thyroiditis (AST) is an uncommon condition because thyroid gland is remarkably resistant to infections . In children, anatomic defects such as a left pyriform sinus fistula or a thyroglossal duct remnant predispose to this infection . Once the diagnosis is confirmed by ultrasound or computed tomography, antimicrobial therapy based on the culture and Gram staining must be started . After two or three weeks of treatment, predisposing anatomic defects must be sought cautiously . We report a 13 year old girl presenting with cervical pain and fever . A cervical ultrasound showed an enlarged thyroid lobule with hypoecogenic zones that suggested a supurative collection . Cefotaxime and cloxacillin were started . A needle aspiration of the collection obtained a purulent material . The culture of this material yielded a Streptococcus Pneumoniae . The clinical condition of the patient improved and she was discharged in good conditions . Two months later a contrast esophagus X ray did not show predisposing anatomic defects.

Head Neck, 2004 Oct, 26(10), 854 - 60
Deep neck infection: analysis of 185 cases; Huang TT et al.; PURPOSE: This study reviews our experience with deep neck infections and tries to identify the predisposing factors of life-threatening complications . METHODS: A retrospective review was conducted of patients who were diagnosed as having deep neck infections in the Department of Otolaryngology at National Taiwan University Hospital from 1997 to 2002 . Their demographics etiology, associated systemic diseases, bacteriology, radiology, treatment, duration of hospitalization, complications, and outcomes were reviewed . The attributing factors to deep neck infections, such as the age and systemic diseases of patients, were also analyzed . RESULTS: One hundred eighty-five charts were recorded; 109 (58.9%) were men, and 76 (41.1%) were women, with a mean age of 49.5 +/- 20.5 years . Ninety-seven (52.4%) of the patients were older than 50 years old . There were 63 patients (34.1%) who had associated systemic diseases, with 88.9% (56/63) of those having diabetes mellitus (DM) . The parapharyngeal space (38.4%) was the most commonly involved space . Odontogenic infections and upper airway infections were the two most common causes of deep neck infections (53.2% and 30.5% of the known causes) . Streptococcus viridans and Klebsiella pneumoniae were the most common organisms (33.9%, 33.9%) identified through pus cultures . K . pneumoniae was also the most common infective organism (56.1%) in patients with DM . Of the abscess group (142 patients), 103 patients (72.5%) underwent surgical drainages . Thirty patients (16.2%) had major complications during admission, and among them, 18 patients received tracheostomies . Those patients with underlying systemic diseases or complications or who received tracheostomy tended to have a longer hospital stay and were older . There were three deaths (mortality rate, 1.6%) . All had an underlying systemic disease and were older than 72 years of age . CONCLUSIONS: When dealing with deep neck infections in a high-risk group (older patients with DM or other underlying systemic diseases) in the clinic, more attention should be paid to the prevention of complications and even the possibility of death . Early surgical drainage remains the main method of treating deep neck abscesses . Therapeutic needle aspiration and conservative medical treatment are effective in selective cases such as those with minimal abscess formation . (c) 2004 Wiley Periodicals, Inc.

Eye . 2004 Sep 24; {Epub ahead of print}
A model for the management of an atypical endophthalmitis outbreak; Anderson OA et al.; PURPOSE OF STUDY: To present a model for the assessment, investigation, and management of an atypical outbreak of infectious endophthalmitis of indeterminate aetiology . METHODS: A published statistical model was used to determine when the case-load constituted an outbreak . Intraocular surgery was discontinued and a multidisciplinary infection control team was formed aimed at identifying potential causative factors among the following categories: environment around theatre, preoperative preparation, intraoperative theatre practices, intraoperative surgical practices, postoperative practices, equipment maintenance guidelines, cleaning/sterilization practices, and microbiological screening . RESULTS: Five cases of postoperative endophthalmitis developed following uncomplicated phacoemulsification cataract surgery by different surgeons over a 7-month period . Despite full investigation no single focus of infection could be determined . Four out of five cases were culture positive . Three grew Streptococcus viridans of different strains . The fourth culture grew Staphylococcus aureus . In the absence of a single causative factor, it was postulated the combined effect of multiple potential factors may have led to an increased bacterial load and subsequent infection rate . Improved practices were initiated including new cleaning protocols to combat the build-up of debris on phacoemulsification instruments . Cataract surgery was resumed with 3-monthly microbiological monitoring . There have been no further cases in the 12 months following the changes . CONCLUSION: Outbreaks of endophthalmitis typically present over a short time period and could often be attributed to a single infective cause . We present our experience of detecting and managing this cluster and recommend a 'ground-up' multidisciplinary model to manage future outbreaks of this devastating condition.Eye advance online publication, 24 September 2004; doi:10.1038/sj.eye.6701695

Acta Crystallogr D Biol Crystallogr, 2004 Oct, 60(Pt 10), 1910 - 1 Epub 2004 Sep 23.
Crystallization of GcnA, an N-acetyl-beta-D-glucosaminidase, from Streptococcus gordonii; Langley DB et al.; Streptococcus gordonii is a primary colonizer of the surface of human teeth . The gcnA gene is one of a number of genes involved in glycoside metabolism . GcnA has N-acetyl-beta-D-glucosaminidase (EC 3.2.1.52) activity; it has been overexpressed, purified and crystallized . Diffraction has been observed to beyond 1.5 A resolution and synchrotron data have been recorded to 1.55 A resolution . The crystals belong to the orthorhombic space group P2(1)2(1)2, with unit-cell parameters a = 112.5, b = 104.0, c = 110.0 A . The crystals contain either a monomer or a dimer in the asymmetric unit.

Int J Syst Evol Microbiol, 2004 Sep, 54(Pt 5), 1753 - 6
Streptococcus halichoeri sp . nov., isolated from grey seals (Halichoerus grypus); Lawson PA et al.; Phenotypic and phylogenetic studies were performed on six unidentified, Gram-positive, catalase-negative, chain-forming Streptococcus-like organisms recovered from grey seals . Biochemically the six strains were highly related to each other, but they did not appear to correspond to any recognized species of the genus Streptococcus . Comparative 16S rRNA gene sequencing studies confirmed that phylogenetically the strains were members of the genus Streptococcus, but sequence divergence values of greater than 3 % compared with reference streptococcal species demonstrated that the organisms from seals represent a novel species . SDS-PAGE analysis of whole-cell proteins confirmed the phenotypic distinctiveness of the seal organisms . Based on biochemical criteria and molecular chemical and genetic evidence, it is proposed that the unknown organism from seals be classified as a novel species, Streptococcus halichoeri sp . nov., the type strain of which is CCUG 48324T (= CIP 108195T).

Int J Syst Evol Microbiol, 2004 Sep, 54(Pt 5), 1505 - 10
Vagococcus carniphilus sp . nov., isolated from ground beef; Shewmaker PL et al.; Nine enterococcus-like strains were referred to the Streptococcus Laboratory at the Centers for Disease Control and Prevention (CDC) for further identification from the National Antimicrobial Resistance Monitoring System Laboratory at the CDC . The cultures were isolated from ground beef purchased from retail in Oregon in 2000 . Conventional biochemical testing and analysis of whole-cell protein electrophoretic profiles distinguished these strains from known species of enterococci and vagococci . Comparative 16S rRNA gene sequencing studies revealed that these strains were most closely related to the species Vagococcus fluvialis . DNA-DNA reassociation studies confirmed that these nine strains represented a new taxon . The relative binding ratio was 87 % or greater at the optimal temperature, and the divergence was less than 1 % for strains hybridized against the isolate designated the type strain . DNA-DNA relatedness was 25 % to V . fluvialis and 9 % or less to the other three species of Vagococcus . DNA-DNA relatedness was 33 % or less to the 25 currently described species of Enterococcus . On the basis of this evidence, it is proposed that these strains be classified as Vagococcus carniphilus sp . nov . The type strain of V . carniphilus is 1843-02T (= ATCC BAA-640T = CCUG 46823T) . The clinical significance (if any) of these strains is yet to be determined.

Antimicrob Agents Chemother, 2004 Oct, 48(10), 4040 - 1
Resistance phenotypes and genotypes of erythromycin-resistant Streptococcus pneumoniae isolates in Beijing and Shenyang, China; Tiemei Z et al.; Of a total of 192 Streptococcus pneumoniae isolates, 149 (77.6%) were not susceptible to erythromycin . Of these 149 isolates, 117 (79.1%) contained the erm(B) gene, 16 (10.8%) contained the mef(A) gene, and 15 (10.1%) harbored both the erm(B) and mef(A) genes.

Antimicrob Agents Chemother, 2004 Oct, 48(10), 4020 - 2
Alterations of penicillin-binding proteins 1A, 2X, and 2B in Streptococcus pneumoniae isolates for which amoxicillin MICs are higher than penicillin MICs; Kosowska K et al.; Penicillin-binding proteins (PBPs) of 15 selected penicillin- and amoxicillin-resistant Streptococcus pneumoniae isolates (MICs of 2 to 8 and 8 to 16 microg/ml, respectively) were studied . In addition to typical changes in PBPs 1A and 2X, these strains had 10 unique changes in PBP 2B, including a (618)A-G substitution, which may be the key alteration associated with amoxicillin resistance.

Antimicrob Agents Chemother, 2004 Oct, 48(10), 3954 - 8
Mutant prevention concentrations for single-step fluoroquinolone-resistant mutants of wild-type, efflux-positive, or ParC or GyrA mutation-containing Streptococcus pneumoniae isolates; Smith HJ et al.; Three fluoroquinolone-susceptible and five fluoroquinolone-resistant (two with ParC Ser79Phe mutations, one with a GyrA Ser81Phe mutation, and two that were efflux positive) Streptococcus pneumoniae isolates were exposed to one, two, four, eight, and sixteen times the MICs of ciprofloxacin, gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin . Mutational frequencies were calculated at each multiple of the MIC for which growth was observed . Mutant prevention concentrations (MPCs) and the multiple of the MIC at the MPC (MP(MIC)) were evaluated . All resulting mutants were sequenced for quinolone resistance-determining region changes in GyrA and ParC and were evaluated for reserpine-sensitive efflux . The MPC order was generally ciprofloxacin > levofloxacin > gatifloxacin > moxifloxacin > gemifloxacin . The MP(MIC) order varied depending on the genetic constitution of the original isolates from which the mutants were generated . For those mutants created from fluoroquinolone-susceptible isolates (those that had wild-type ParC and GyrA and were efflux negative), the MP(MIC) order was ciprofloxacin = moxifloxacin > gemifloxacin > levofloxacin > gatifloxacin . The MP(MIC)s of each fluoroquinolone for mutants created from isolates with a ParC mutation (with wild-type GyrA and efflux negative) were similar . A similar occurrence was observed with the mutants created from the efflux-positive isolates (with wild-type ParC and GyrA) . The MP(MIC) order for the mutants created from the isolate with a GyrA mutation (with wild-type ParC and efflux negative) was ciprofloxacin = gemifloxacin > levofloxacin = moxifloxacin > gatifloxacin . Gatifloxacin, levofloxacin, and moxifloxacin may be intrinsically more able to prevent the development of resistance by fluoroquinolone-susceptible isolates, isolates that are efflux positive, or isolates that carry a GyrA mutation . However, once a ParC mutation is present, the MPC increases dramatically for all fluoroquinolones.

Antimicrob Agents Chemother, 2004 Oct, 48(10), 3928 - 33
Daptomycin is highly efficacious against penicillin-resistant and penicillin- and quinolone-resistant pneumococci in experimental meningitis; Cottagnoud P et al.; The penetration of daptomycin, a new lipopeptide antibiotic, into inflamed meninges ranged between 4.37 and 7.53% (mean, 5.97%) . Daptomycin was very efficacious in the treatment of experimental pneumococcal meningitis, producing a decrease of -1.20 +/- 0.32 Deltalog(10) CFU/ml . h in the bacterial titer of Streptococcus pneumoniae against a penicillin-resistant strain and of -0.97 +/- 0.32 Deltalog(10) CFU/ml . h against a penicillin- and quinolone-resistant strain found in cerebrospinal fluid (CSF) . For both strains, daptomycin was significantly superior to the standard regimen of a combination of ceftriaxone with vancomycin, sterilizing 9 of 10 CSF samples after 4 h . In vitro, daptomycin produced highly bactericidal activity in concentrations above the MIC.

Antimicrob Agents Chemother, 2004 Oct, 48(10), 3697 - 701
Antimicrobial evaluation of nocathiacins, a thiazole peptide class of antibiotics; Pucci MJ et al.; Nocathiacins are cyclic thiazolyl peptides with inhibitory activity against gram-positive bacteria . BMS-249524 (nocathiacin I), identified from screening a library of compounds against a multiply antibiotic-resistant Enterococcus faecium strain, was used as a lead chemotype to obtain additional structurally related compounds . The MIC assay results of BMS-249524 and two more water-soluble derivatives, BMS-411886 and BMS-461996, revealed potent in vitro activities against a variety of gram-positive pathogens including methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae, vancomycin intermediate-resistant S . aureus, vancomycin-resistant enterococci, Mycobacterium tuberculosis and Mycobacterium avium . Analysis of killing kinetics revealed that these compounds are bactericidal for S . aureus with at least a 3-log(10) reduction of bacterial growth within 6 h of exposure to four times the MICs . Nocathiacin-resistant mutants were characterized by DNA sequence analyses . The mutations mapped to the rplK gene encoding the L11 ribosomal protein in the 50S subunit in a region previously shown to be involved in the binding of related thiazolyl peptide antibiotics . These compounds demonstrated potential for further development as a new class of antibacterial agents with activity against key antibiotic-resistant gram-positive bacterial pathogens.

J Mater Sci Mater Med, 2004 Jul, 15(7), 831 - 7
Antibacterial and bioactive silver-containing Na2O x CaO x 2SiO2 glass prepared by sol-gel method; Catauro M et al.; The antibacterial effect of addition of silver oxide to Na2O x CaO x 2SiO2 glass have been studied . Silver containing and silver free Na2O x CaO x 2SiO2 glasses have been prepared by sol-gel synthesis using tetramethil orthosilicate, sodium ethoxide, calcium nitrate tetrahydrate and silver nitrate as starting materials and methyl ethyl ketone as solvent . The gel was examined by differential thermal analysis, thermo gravimetric analysis, FTIR spectroscopy and X-ray diffraction analysis . Antibacterial and bioactive tests on gel glass powders, obtained after a heat treatment of 2 h at 600 degrees C of the dried gel, were carried out . High antimicrobial effects of samples against Escherichia coli and Streptococcus mutans were found . FTIR measurements and SEM micrographs have ascertained the formation of a hydroxyapatite layer on the surface of samples soaked in a simulated body fluid for different times.

J Am Dent Assoc, 2004 Aug, 135(8), 1133 - 41
The antimicrobial potential of 14 natural herbal dentifrices: results of an in vitro diffusion method study; Lee SS et al.; BACKGROUND: Increasing numbers of Americans are using natural herbal products for general and oral health care . Few of these products, however, have undergone rigorous testing, as evidenced by the limited amount of information on their safety and efficacy in the literature . The authors conducted an in vitro study to evaluate the antimicrobial potential of 14 natural herbal dentifrices . METHODS: The authors used a diffusion method to evaluate the antimicrobial effectiveness of 14 natural herbal dentifrices against four microorganisms: Streptococcus mutans, Streptococcus sanguis, Actinomyces viscosus and Candida albicans . Colgate Total (Colgate-Palmolive, New York City) and sterile pyrogen-free water served as the positive and negative controls, respectively . The authors tested the natural herbal dentifrices at full strength and at 1:1 dilution . They measured the zones of inhibition at 24 and 48 hours to evaluate the antimicrobial potential of the dentifrices . RESULTS: Six herbal dentifrices were effective in inhibiting the growth of all four microorganisms . The positive control produced significantly sized inhibition zones with all four microorganisms, while the negative control produced no observable zones . Six herbal dentifrices produced larger inhibition zones with A . viscosus than did the positive control . Six herbal dentifrices were inhibitory against C . albicans at full strength, but at 1:1 dilution, only three had such inhibitory effect . One herbal dentifrice produced microbial growth around and over the samples, indicating possible microbial contamination of the toothpaste . Only one herbal dentifrice showed consistent antimicrobial activity against all four microorganisms . CONCLUSIONS: The variation in antimicrobial inhibition among the herbal dentifrices indicates that more research is needed to validate their effectiveness claims . CLINICAL IMPLICATIONS: This study provides practitioners with insight into the claims of natural herbal dentifrices' antimicrobial effects.

Curr Microbiol, 2004 Oct, 49(4), 239 - 47
An examination of the differential sensitivity to ketolide antibiotics in ermB strains of Streptococcus pyogenes and Streptococcus pneumoniae; Champney WS et al.; Several reports in the literature have described a differential sensitivity to ketolide antibiotics in ermB strains of Streptococcus pyogenes and Streptococcus pneumoniae resistant to erythromycin . Strains of S . pyogenes and S . pneumoniae carrying different erm gene alleles were examined for their susceptibility to the ketolide antibiotics cethromycin (ABT-773) and telithromycin . The effect of the antibiotics on cell growth and viability was assessed as were effects on protein synthesis and 50S ribosomal subunit formation . The susceptibility of wild-type strains of both organisms was compared with effects in strains containing the ermA and ermB methyltransferase genes . A wild-type antibiotic-susceptible strain of S . pyogenes was comparable to an ermA strain of the organism in its ketolide sensitivity, with IC(50) values for 50% inhibition of protein synthesis and 50S ribosomal subunit formation of 10 ng/mL for cethromycin and 16 ng/mL for telithromycin . An S . pneumoniae strain with the ermB gene and an S . pyogenes strain with the ermA gene were also similar in their sensitivity to ketolide inhibition . IC(50) values for inhibition of translation and subunit formation in S . pneumoniae ( ermB) were 30 ng/mL and 55 ng/mL and for the ermA strain of S . pyogenes they were 15 ng/mL and 35 ng/mL respectively . By contrast, an S . pyogenes ermB strain was significantly more resistant to both ketolides, with IC(50) values for inhibition of 50S synthesis of 215 and 380 ng/mL for the two ketolides . Experiments were conducted to examine ribosome synthesis and translational activity in the two ermB strains at intervals during growth in the presence of each antibiotic . Cell viability and 50S subunit formation were dramatically reduced in the S . pneumoniae strain during continued growth with either drug . By contrast, the ketolides had little effect on the S . pyogenes strain growing with the antibiotics . The results indicate that ketolides have a reduced inhibitory effect on translation and 50S subunit synthesis in S . pyogenes with the ermB gene compared with the other strains examined.

Infect Immun, 2004 Oct, 72(10), 6181 - 4
A peptide domain of bovine milk lactoferrin inhibits the interaction between streptococcal surface protein antigen and a salivary agglutinin peptide domain; Oho T et al.; The peptide domain of salivary agglutinin responsible for its interaction with cell surface protein antigen (PAc) of Streptococcus mutans or bovine lactoferrin was found in the same peptide, scavenger receptor cysteine-rich domain peptide 2 (SRCRP2) . Inhibition studies suggest that PAc and lactoferrin, of which residues 480 to 492 seem important, competitively bind to the SRCRP2 domain of salivary agglutinin.

Infect Immun, 2004 Oct, 72(10), 6068 - 75
The Streptococcus pyogenes capsule is required for adhesion of bacteria to virus-infected alveolar epithelial cells and lethal bacterial-viral superinfection; Okamoto S et al.; An apparent worldwide resurgence of invasive group A Streptococcus (GAS) infections remains unexplained . However, we recently demonstrated in mice that when an otherwise nonlethal intranasal GAS infection is preceded by a nonlethal influenza A virus (IAV) infection, induction of lethal invasive GAS infections is often the result . In the present study, we established several isogenic mutants from a GAS isolate and evaluated several virulence factors as candidates responsible for the induction of invasive GAS infections . Disruption of the synthesis of the capsule, Mga, streptolysin O, streptolysin S, or streptococcal pyrogenic exotoxin B of GAS significantly reduced mortality among mice superinfected with IAV and a mutant . In addition, the number of GAS organisms adhering to IAV-infected alveolar epithelial cells was markedly reduced with the capsule-depleted mutant, although this was not the case with the other mutants . Wild-type GAS was found to bind directly to IAV particles, whereas the nonencapsulated mutant showed much less ability to bind . These results suggest that the capsule plays a key role in the invasion of host tissues by GAS following superinfection with IAV and GAS.

Infect Immun, 2004 Oct, 72(10), 5858 - 67
Lipoprotein PsaA in virulence of Streptococcus pneumoniae: surface accessibility and role in protection from superoxide; Johnston JW et al.; PsaA of Streptococcus pneumoniae, originally believed to be an adhesin, is the lipoprotein component of an Mn2+ transporter . Mutations in psaA cause deficiencies in growth, virulence, adherence, and the oxidative stress response . Immunofluorescence microscopy shows that PsaA is hidden beneath the cell wall and the polysaccharide capsule and only exposed to antibodies upon cell wall removal . A psaBC deletion mutant, expressing PsaA normally, was as deficient in adherence to Detroit 562 cells as were strains lacking PsaA . Thus, PsaA does not appear to act directly as an adhesin, but rather, psaA mutations indirectly affect this process through the disruption of Mn2+ transport . The deficiency in Mn2+ transport also causes hypersensitivity to oxidative stress from H2O2 and superoxide . In a chemically defined medium, growth of the wild-type strain was possible in the absence of Fe2+ and Mn2+ cations after a lag of about 15 h . Addition of Mn2+ alone or together with Fe2+ allowed prompt and rapid growth . In the absence of Mn2+, the addition of Fe2+ alone extended the 15-h lag phase to 25 h . Thus, while Fe2+ adversely affects the transition from lag phase to log phase, perhaps through increasing oxidative stress, this effect is relieved by the presence of Mn2+ . A scavenger specific for superoxides but not those specific for hydroxyl radicals or H2O2 was able to eliminate the inhibition of growth caused by iron supplementation in the absence of Mn2+ . This implies that superoxides are a key player in oxidative stress generated in the presence of iron.

Infect Immun, 2004 Oct, 72(10), 5807 - 13
Limited role of antibody in clearance of Streptococcus pneumoniae in a murine model of colonization; McCool TL et al.; Colonization is the first step in the interaction between Streptococcus pneumoniae and its human host . To better understand the mechanisms contributing to natural carriage, a mouse model of pneumococcal colonization was developed with a clinical isolate of S . pneumoniae previously characterized in experimental colonization of humans . Similar to carriage events in humans, colonization of mice was self-limited and there was no evidence of lower respiratory tract or invasive disease . Carriage induced a serum antibody response to whole pneumococci that was associated temporally with clearance of colonization in three inbred strains of mice . Individual mice, however, did not demonstrate a correlation between the density of colonization and amounts of serum or of mucosal antibodies, including antibodies of different isotypes and antigenic specificities . The role of antibody in the clearance of carriage was then examined in mice with genetic defects in humoral immunity . xid mice, which have deficient responses to polysaccharide antigens, cleared colonization at the same rate as the parent strain . Finally, we showed that microMT mice, which lack mature B cells and fail to produce antibody, were unaffected in the density or duration of colonization . These results demonstrate that antibody is not required for clearance of pneumococcal colonization in mice.

Infect Immun, 2004 Oct, 72(10), 5646 - 53
The ClpP protease of Streptococcus pneumoniae modulates virulence gene expression and protects against fatal pneumococcal challenge; Kwon HY et al.; Streptococcus pneumoniae usually colonizes the nasopharynx of humans asymptomatically but occasionally translocates from this niche to the lungs, the brain, and the blood, causing potentially fatal infections . Spread to other host tissues requires a significant morphological change and the expression of virulence factors, such as capsular polysaccharide, and virulence proteins, such as pneumolysin (Ply), PspA, and CbpA . Modulation of the expression of pneumococcal virulence genes by heat shock and by heat shock proteins ClpL and ClpP, as well as the attenuation of virulence of a clpP mutant in a murine intraperitoneal infection model, was demonstrated previously . In this study, we further investigated the underlying mechanism of virulence attenuation by the clpP mutation . The half-lives of the mRNAs of ply and of the first gene of the serotype 2 capsule synthesis locus {cps2A} in the clpP mutant were more than twofold longer than those of the parent after heat shock, suggesting that the mRNA species were regulated posttranscriptionally by ClpP . In addition, the clpP mutant was defective in colonization of the nasopharynx and survival in the lungs of mice after intranasal challenge . The mutant was also killed faster than the parent in the murine macrophage RAW264.7 cell line, indicating that ClpP is required for colonization and intracellular survival in the host . Furthermore, fractionation studies demonstrated that ClpP was translocated into the cell wall after heat shock, and immunization of mice with ClpP elicited a protective immune response against fatal systemic challenge with S . pneumoniae D39, making ClpP a potential vaccine candidate for pneumococcal disease.

Infect Immun, 2004 Oct, 72(10), 5582 - 96
Microarray analysis of pneumococcal gene expression during invasive disease; Orihuela CJ et al.; Streptococcus pneumoniae is a leading cause of invasive bacterial disease . This is the first study to examine the expression of S . pneumoniae genes in vivo by using whole-genome microarrays available from The Institute for Genomic Research . Total RNA was collected from pneumococci isolated from infected blood, infected cerebrospinal fluid, and bacteria attached to a pharyngeal epithelial cell line in vitro . Microarray analysis of pneumococcal genes expressed in these models identified body site-specific patterns of expression for virulence factors, transporters, transcription factors, translation-associated proteins, metabolism, and genes with unknown function . Contributions to virulence predicted for several unknown genes with enhanced expression in vivo were confirmed by insertion duplication mutagenesis and challenge of mice with the mutants . Finally, we cross-referenced our results with previous studies that used signature-tagged mutagenesis and differential fluorescence induction to identify genes that are potentially required by a broad range of pneumococcal strains for invasive disease.

BMC Microbiol . 2004 Sep 22;4(1):36.
Method for inducing experimental pneumococcal meningitis in outbred mice; Chiavolini D et al.; BACKGROUND: Streptococcus pneumoniae is the leading cause of bacterial meningitis . Pneumococcal meningitis is associated with the highest mortality among bacterial meningitis and it may also lead to neurological sequelae despite the use of antibiotic therapy . Experimental animal models of pneumococcal meningitis are important to study the pathogenesis of meningitis, the host immune response induced after infection, and the efficacy of novel drugs and vaccines . RESULTS: In the present work, we describe in detail a simple, reproducible and efficient method to induce pneumococcal meningitis in outbred mice by using the intracranial subarachnoidal route of infection . Bacteria were injected into the subarachnoid space through a soft point located 3.5 mm rostral from the bregma . The model was tested with several doses of pneumococci of three capsular serotypes (2, 3 and 4), and mice survival was recorded . Lethal doses killing 50 % of animals infected with type 2, 3 and 4 S . pneumoniae were 3.2 x 10, 2.9 x 10 and 1.9 x 10(2) colony forming units, respectively . Characterisation of the disease caused by the type 4 strain showed that in moribund mice systemic dissemination of pneumococci to blood and spleen occurred . Histological analysis of the brain of animals infected with type 4 S . pneumoniae proved the induction of meningitis closely resembling the disease in humans . CONCLUSIONS: The proposed method for inducing pneumococcal meningitis in outbred mice is easy-to-perform, fast, cost-effective, and reproducible, irrespective of the serotype of pneumococci used.

J Immunol, 2004 Oct 1, 173(7), 4576 - 81
An important role for polymeric Ig receptor-mediated transport of IgA in protection against Streptococcus pneumoniae nasopharyngeal carriage; Sun K et al.; The importance of IgA for protection at mucosal surfaces remains unclear, and in fact, it has been reported that IgA-deficient mice have fully functional vaccine-induced immunity against several bacterial and viral pathogens . The role of respiratory Ab in preventing colonization by Streptococcus pneumoniae has now been examined using polymeric IgR knockout (pIgR(-/-)) mice, which lack the ability to actively secrete IgA into the mucosal lumen . Intranasal vaccination with a protein conjugate vaccine elicited serotype-specific anti-capsular polysaccharide Ab locally and systemically, and pIgR(-/-) mice produced levels of total serum Ab after vaccination that were similar to wild-type mice . However, pIgR(-/-) mice had approximately 5-fold more systemic IgA and 6-fold less nasal IgA Ab than wild-type mice due to defective transport into mucosal tissues . Wild-type, but not pIgR(-/-) mice were protected against infection with serotype 14 S . pneumoniae, which causes mucosal colonization but does not induce systemic inflammatory responses in mice . The relative importance of secretory IgA in host defense was further shown by the finding that intranasally vaccinated IgA gene-deficient mice were not protected from colonization . Although secretory IgA was found to be important for protection against nasal carriage, it does not appear to have a crucial role in immunity to systemic pneumococcus infection, because both vaccinated wild-type and pIgR(-/-) mice were fully protected from lethal systemic infection by serotype 3 pneumococci . The results demonstrate the critical role of secretory IgA in protection against pneumococcal nasal colonization and suggest that directed targeting to mucosal tissues will be needed for effective vaccination in humans.

J Med Food, 2004 Fall, 7(3), 381 - 4
Natural products for dental caries prevention; Badria FA et al.; Selected natural compounds were evaluated for their effects on dental caries due to different strains of Streptococcus mutans bacteria . Out of 39 tested compounds, four (catechol, emetine, quinine, and flavone) showed potent inhibitory activity on different strains of S . mutans at 6.25 microg/mL or less with inhibition of adherence <50%, two compounds (5,7-dihydroxy-4'-methoxy isoflavone and ellagic acid) exhibited a moderate inhibitory effect at 12.5 microg/mL with inhibition to adherence <50%, and 12 compounds exhibited weak antibacterial activity at 125 microg/mL or more with inhibition of adherence <25% . These compounds represent three major classes of natural products: tannins, alkaloids, and flavonoids . Further study for possible application of these compounds as inhibitors for dental caries is underway.

Microb Drug Resist, 2004 Fall, 10(3), 264 - 8
Prevalence of the internalization-associated gene prtF1 in a bacterial population of Streptococcus pyogenes isolated from children with acute pharyngotonsillitis before and after antibiotic therapy; Cocuzza CE et al.; The prevalence of the internalization-associated prtF1 gene was studied in 837 isolates of Streptococcus pyogenes obtained from 713 pediatric patients presenting with acute pharyngotonsillitis before and after antibiotic therapy . Its association with macrolide resistance and with bacteriological treatment failure was determined . The bacterial population isolated from baseline pharyngeal swabs showed an overall prtF1 positivity rate of 33% . A higher prtF1 positivity was found among erythromycin-resistant strains (45%) showing, however, marked differences between the inducible (iMLS), constitutive (cMLS), and efflux pump (M) resistance phenotypes . The prevalence was statistically higher (p < 0.001) in strains belonging to iMLS (84%) and cMLS (67%) phenotypes as compared to the M phenotype (15%) . Interestingly, the prevalence of the prtF1 gene was significantly lower (p = 0.04) in strains belonging to M resistance phenotype as compared to erythromycin-susceptible strains (28%) . Failed bacterial eradication was demonstrated in 124 patients . The prtF1 positivity rate remained unchanged in strains isolated before and after therapy in patients treated with macrolides (9/54) . On the other hand, the positivity rate for the prtF1 gene was significantly higher (p = 0.015) in strains isolated after therapy with beta-lactams (21/70) as compared to baseline isolates (6/70), indicating a differential selection imposed on the organism by these agents . Finally, a high overall eradication rate (88%) of prtF1-positive isolates, belonging to both the erythromycin-susceptible and -resistant phenotypes, was demonstrated following macrolide treatment . Copyright Mary Ann Liebert, Inc.

Microb Drug Resist, 2004 Fall, 10(3), 231 - 8
Tetracycline and macrolide co-resistance in Streptococcus pyogenes: co-selection as a reason for increase in macrolide-resistant S . pyogenes?
Nielsen HU, Hammerum AM, Ekelund K, Bang D, Pallesen LV, Frimodt-Moller N.
In Denmark, tetracycline resistance in Streptococcus pyogenes is frequent (>30%) whereas macrolide resistance is low (<5%) . The aim of this study was to investigate the genetic background of tetracycline- and macrolide resistance in macrolide-resistant S . pyogenes (MRSP) and to investigate the correlation between the use of macrolide and tetracycline and macrolide resistance using international data . A total of 133 MRSP isolates were received at Statens Serum Institut from nine Danish clinical microbiology laboratories between . November 2000, and November 2002 . The macrolide-resistance genes, erm(B), erm(A), and mef(A) were detected in 46%, 18%, and 32% of the tested MRSP isolates, respectively . In 4% of MRSP isolates, none of the MR genes were detected . Tetracycline resistance was found in 52% of MRSP . Tetracycline resistance was encoded by either tet(M) or tet(O) . erm(B) and mef(A) were associated with tet(M) . Sixteen different T types were detected among the 133 MRSP . Analysis of the importance of antibiotic use for development of macrolide resistance in S . pyogenes showed no correlation with macrolide use alone (p = 0.15) but a significant correlation (p = 0.03) for the combination of macrolide and tetracycline use . The frequency of macrolide resistance in Danish S . pyogenes was low and mainly due to erm genes . A high frequency of macrolide-tetracycline coresistance in S . pyogenes is found in many countries including Denmark, hence tetracycline use must be considered as a co-factor in selection of MRSP . Copyright Mary Ann Liebert, Inc.

Microb Drug Resist, 2004 Fall, 10(3), 209 - 17
Molecular characterization of clinical Streptococcus pneumoniae isolates with reduced susceptibility to fluoroquinolones emerging in Italy; Montanari MP et al.; Fifteen Streptococcus pneumoniae clinical isolates with reduced fluoroquinolone susceptibility (defined as a ciprofloxacin MIC of > or = 4 microg/ml), all collected in Italy in 2000-2003, were typed and subjected to extensive molecular characterization to define the contribution of drug target alterations and efflux mechanisms to their resistance . Serotyping and pulsed-field gel electrophoresis analysis indicated substantial genetic unrelatedness among the 15 isolates, suggesting that the new resistance traits arise in multiple indigenous strains rather than through clonal dissemination . Sequencing of the quinolone resistance-determining regions of gyrA, gyrB, parC, and parE demonstrated that point mutations producing single amino acid changes were more frequent in topoisomerase IV (parC mutations in 14 isolates and parE mutations in 13) than in DNA gyrase subunits (gyrA mutations in 7 isolates and no gyrB mutations observed) . No isolate displayed a quinolone efflux system susceptible to carbonyl cyanide m-chlorophenylhydrazone; conversely, four-fold or greater MIC reductions in the presence of reserpine were observed in all 15 isolates with ethidium bromide, in 13 with ulifloxacin, in 9 with ciprofloxacin, in 5 with norfloxacin, and in none with five other fluoroquinolones . The effect of efflux pump activity on the level and profile of fluoroquinolone resistance in our strains was minor compared with that of target site modifications . DNA mutations and/or efflux systems other than those established so far might contribute to the fluoroquinolone resistance expressed by our strains . Susceptibility profiles to nonquinolone class antibiotics and resistance-associated phenotypic and genotypic characteristics were also determined and correlated with fluoroquinolone resistance . A unique penicillin-binding protein profile was observed in all five penicillin-resistant isolates, whereas the same PBP profile as S . pneumoniae R6 was exhibited by all six penicillin-susceptible isolates . This is the first attempt to molecularly characterize clinical isolates of S . pneumoniae with reduced susceptibility to fluoroquinolones emerging in Italy . Copyright Mary Ann Liebert, Inc.

Proc Natl Acad Sci U S A, 2004 Oct 5, 101(40), 14491 - 6 Epub 2004 Sep 20.
Sword and shield: linked group B streptococcal beta-hemolysin/cytolysin and carotenoid pigment function to subvert host phagocyte defense; Liu GY et al.; Group B Streptococcus (GBS) is a major cause of pneumonia, bacteremia, and meningitis in neonates and has been found to persist inside host phagocytic cells . The pore-forming GBS beta-hemolysin/cytolysin (betaH/C) encoded by cylE is an important virulence factor as demonstrated in several in vivo models . Interestingly, cylE deletion results not only in the loss of betaH/C activity, but also in the loss of a carotenoid pigment of unknown function . In this study, we sought to define the mechanism(s) by which cylE may contribute to GBS phagocyte resistance and increased virulence potential . We found that cylE-deficient GBS was more readily cleared from a mouse's bloodstream, human whole blood, and isolated macrophage and neutrophil cultures . Survival was linked to the ability of betaH/C to induce cytolysis and apoptosis of the phagocytes . At a lower bacterial inoculum, cylE also contributed to enhanced survival within phagocytes that was attributed to the ability of carotenoid to shield GBS from oxidative damage . In oxidant killing assays, cylE mutants were shown to be more susceptible to hydrogen peroxide, hypochlorite, superoxide, and singlet oxygen . Together, these data suggest a mechanism by which the linked cylE-encoded phenotypes, betaH/C (sword) and carotenoid (shield), act in partnership to thwart the immune phagocytic defenses.

Vet Microbiol, 2004 Oct 5, 103(1-2), 55 - 62
Characterization of Streptococcus suis serotype 7 isolates from diseased pigs in Denmark; Tian Y et al.; Isolates of Streptococcus suis serotype 7 from diseased pigs in Denmark were characterized by ribotyping, pulsed field gel electrophoresis (PFGE), MIC-determinations and detection of resistance genes . Forty-one different ribotype profiles were found among the 103 isolates and could be divided into two main clusters . No obvious relationship between ribotypes and the clinical origin of the isolates could be observed . Fifty-four isolates, including all 24 isolates belonging to the main ribotype profile were examined by PFGE and 50 different profiles were found . A high frequency of resistance to erythromycin (41%), tetracycline (24%) and streptomycin (28%) was observed . Furthermore, almost all isolates (101) were resistant to sulphamethoxazol . Most isolates were susceptible to ceftiofur, chloramphenicol, florfenicol, penicillin, ciprofloxacin, trimethoprim and trimethoprim + sulphonamides . The tet(M) gene was found among 11 (44%) and the tet(O) gene in six (24%) of 25 tetracycline resistant isolates . The tet(L) and tet(S) genes were not detected in any isolates . The erm(B) gene was detected in 39 (93%) of 42 erythromycin resistant isolates.

Vet Microbiol, 2004 Oct 5, 103(1-2), 29 - 33
Intestinal translocation of Streptococcus suis type 2 EF+ in pigs; Swildens B et al.; Sepsis with subsequent multisystem organ failure after translocation of bacteria from the gut is a serious risk associated with stress situations . We showed that intestinal bacterial translocation could be one of the pathways for pathogenic Streptococcus suis infections in the pig . In 24 piglets weighing 10-14 kg, free of the extracellular factor (EF+) producing phenotype of S . suis serotype 2, a silicon canula was placed in the proximal jejunum to enable intestinal inoculation and bypassing the upper alimentary tract . The pigs were individually housed . After stress induction in 18 pigs by means of a truck drive in individual cages for 1h, pigs were inoculated through the intestinal canula either with S . suis type 2 EF+ or with growth medium only, and put back in their original housing . The six not transported pigs were also inoculated with the same strain . To prevent oral self-infection, faeces were collected in a bag that was glued around the anus . Clinical and behavioral symptoms were recorded for 72 h post inoculation, and then the animals were sacrificed for pathological and bacteriological examination . In three animals, the inoculation strain was re-isolated from mesenterial lymph nodes and typically affected organs . No S . suis type 2 EF+ was detected by specific polymerase chain reaction (PCR) in any of the tonsil-swabs and -homogenates . We concluded that infection of the organs had taken place after bacterial translocation out of the gut and that the intestinal tract can be a porte d'entree for S . suis type 2 EF+.

J Dermatol Sci, 2004 Sep, 35(3), 187 - 97
Therapeutic effects of streptococcal preparation OK-432 on atopic dermatitis-like lesions in NC/Nga mice: possible shift from a Th2- to Th1-predominance; Horiuchi Y et al.; BACKGROUND: The inducement of Th1 cell-mediated immune response, possibly brought about through bacterial stimulation, may serve to control atopic disorders such as atopic dermatitis (AD) . The streptococcal preparation, OK-432, has been shown a potent Th1 inducer through the action of IL-12 . NC/Nga mice under ordinary conditions have been found to contract dermatitis similar to human AD . OBJECTIVE: Examination was made of the therapeutic effects of OK-432 local intra- and/or subcutaneous injections on AD-like lesions in NC/Nga mice . METHODS: Immunohistochemical staining with IL-4/IL-12p40 and CD80/86 and phosphorylated STAT4/p-STAT6 and RT-PCR for IL-4/IL-12p40 and STAT6/STAT4 mRNA was conducted for the evaluation of OK-432 treatment of spontaneous AD-like lesions in NC/Nga mice . RESULTS: At 5 weeks following injection of OK-432, for treating head and back lesions in NC/Nga mice, 10 of 12 OK-432 treated NC mice were found to have clinically improved quite considerably . On the head and back skin of OK-432-treated mice, IL-12p40/CD80 positive cellular infiltration was conspicuous, in contrast to non-treated mice . IL-4/CD86 positive cellular infiltrates in OK-432-treated mice had decreased significantly more than in non-treated mice and IL-4 mRNA expression was virtually absent in OK-432-treated mice . P-STAT4 positive cells could be seen abundantly present in OK-432-treated mice, and p-STAT6 positive cells were much fewer than in non-treated mice . CONCLUSIONS: OK-432-treatment appears to induce Th1 cellular response and to down-regulate that of the Th2 pathway in AD-like lesions of NC/Nga mice . The present results demonstrate bacterial components from such Streptococcus to likely constitute an effective new therapeutic approach in the treatment of AD .

Drug Discov Today, 2004 Oct 1, 9(19), 831 - 7
Respiratory infections and asthma: current treatment strategies; Weinberger M; Infections such as lower respiratory illness potentially contribute to the initiation of asthma and are major factors in recurring acute exacerbations of the condition . Although typical bacterial respiratory pathogens such as Streptococcus pyogenes, Streptococcus pneumoniae and Hemophilus influenzae do not initiate asthmatic exacerbations, data from a subgroup of adults suggest a potential role for Mycoplasma pneumoniae and Chlamydia pneumoniae in the onset of asthma . Common cold viruses, predominantly respiratory syncytial virus (RSV) in young children and rhinoviruses in older children and adults, are the major causes of acute exacerbations of asthma . These exacerbations are not prevented with maintenance therapies that are used for chronic asthma, but do respond to short courses of systemic corticosteroids . There are continued attempts to produce a successful vaccine and antiviral agents for the treatment of RSV that are more effective and more practical to use than ribavirin, which is currently the only available antiviral for RSV . The prevention and treatment of rhinovirus infections have focused on the major receptor for the virus, intercellular adhesion molecule-1 (ICAM-1), which is located on respiratory epithelial cells . A multivalent, recombinant, antibody fusion protein identified as CFY196 has high avidity for ICAM-1 and has the potential to protect against rhinovirus infection . Another approach for preventing and treating rhinovirus infection uses a recombinant, soluble, truncated form of ICAM-1 in which the transmembrane and intracellular domains of the protein have been deleted . An initial clinical study on this agent demonstrated clinical efficacy in ameliorating the symptoms of experimental rhinovirus infection in volunteers, but did not significantly prevent infection.

Microbes Infect, 2004 Oct, 6(12), 1117 - 23
Streptococcus pyogenes and human neutrophils: a paradigm for evasion of innate host defense by bacterial pathogens; Voyich JM et al.; Human polymorphonuclear leukocytes (PMNs) are the first line of defense against invading microorganisms . Although most invading bacteria are eliminated by PMNs, some have evolved complex strategies to prevent normal PMN function . This review focuses on the interaction of human PMNs with Streptococcus pyogenes as a paradigm for successful pathogen evasion mechanisms.

Int J Antimicrob Agents, 2004 Oct, 24(4), 381 - 5
Influence of thiamphenicol on the primary functions of human polymorphonuclear leucocytes against Streptococcus pyogenes; Tullio V et al.; Current antibiotic therapy encourages the use of antibiotics that may potentiate the host's immune defences . We therefore investigated the effect of thiamphenicol (TAP), the active principle of thiamphenicol glycinate acetylcysteinate (TGA), on human granulocyte functions, mainly phagocytosis and intracellular killing of Streptococcus pyogenes . Our findings support the use of thiamphenicol in the treatment of respiratory tract infections caused by S . pyogenes as it acts directly against the pathogen as well as in cooperation with PMNs by eliciting their intracellular killing.

Int J Antimicrob Agents, 2004 Oct, 24(4), 334 - 8
Bactericidal activity of moxifloxacin against multidrug-resistant Streptoccocus pneumoniae at clinically achievable serum and epithelial lining fluid concentrations compared with three other antimicrobials; Cafini F et al.; Time-kill studies compared the activities of moxifloxacin with those of levofloxacin, azithromycin and amoxicillin-clavulanate against 10 pneumococcal strains with various drug susceptibilities . Three Streptococcus pneumoniae strains were resistant to moxifloxacin: 6, 7 and 2 strains were resistant to levofloxacin, azithromycin and amoxicillin-clavulanate, respectively . Of these, 1 strain was resistant to all antimicrobial agents studied . Moxifloxacin and amoxicillin-clavulanate were bactericidal after 24h at serum Cmax levels against 9 and 8 strains, respectively, while levofloxacin and azithromycin were bactericidal against 3 and 2 strains, respectively . A higher activity was only observed for amoxicillin-clavulanate for logarithmic phase cultures at 1, 4 and 8h compared with stationary phase organisms . Amoxicillin-clavulanate and moxifloxacin were bactericidal at free serum levels (protein unbound) after 24h against 8 and 3 strains, respectively . Moxifloxacin was bactericidal at epithelial lining fluid levels against all strains at 24h, including one moxifloxacin, amoxicillin-clavulanate and azithromycin-resistant strain; lower levels of bactericidal activity was observed for levofloxacin, azithromycin and amoxicillin-clavulanate against 7, 2 and 4 strains, respectively . This demonstrated the importance of moxifloxacin tissue levels.

Curr Drug Targets Infect Disord, 2004 Sep, 4(3), 169 - 76
Macrolide resistance in Streptococcus pneumoniae: clonality and mechanisms of resistance in 24 countries; Bozdogan B et al.; The clonality and mechanisms of macrolide resistance were studied among 345 macrolide resistant Streptococcus pneumoniae strains isolated from 24 countries . The mechanisms of macrolide resistance, serotypes and PFGE types of the strains were determined and representative strains of clones from each country were typed by MLST . Among strains tested 215 had the erm(B) gene, 92 the mef(A) gene, 14 had both erm(B) and mef(A), and 24 had alterations in ribosomal proteins {2 with A2059G substitutions in 23S rRNA, 21 with 69GTG71 to TPS change in L4, and one with erm(B) and deletion of leucine at position 68 in L22} . Serogroups 19, 6, and 23, and serotype 14 were the most common serotypes/serogroups . Dissemination of variants of sequence type (ST) 315 and ST156 were observed in Eastern and Central European countries . In Asiatic countries the most common sequence types were variants of ST236 among strains with mef(A) and ST180 among strains with erm(B) . Strains with both erm(B) and mef(A) from Mexico and Singapore were variants of ST236 . The widespread clone from Slovakia with ribosomal protein L4 mutation was a variant of ST226 . Common clones were observed between Europe, Asia, and America . Overall, while serotypes/serogroups of macrolide resistant isolates were limited, multiple PFGE and MLST types were found, with clustering of common clones within countries.

J Infect Dis, 2004 Oct 15, 190(8), 1481 - 7 Epub 2004 Sep 09.
Tolerance to vancomycin in pneumococci: detection with a molecular marker and assessment of clinical impact; Rodriguez CA et al.; BACKGROUND: Vancomycin is often added to therapy for meningitis caused by Streptococcus pneumoniae . Tolerant bacteria without classic resistance that escape killing by multiple antibiotics have been reported sporadically . We determined the prevalence of tolerance to vancomycin in pneumococci and its effect on the outcome of meningitis . METHODS: Archival samples of 215 nasopharyngeal (NP) and 113 meningitis isolates were tested for the killing efficacy of vancomycin . Specific DNA sequence changes in a transporter locus were identified for tolerant isolates . Similar tests were conducted prospectively on 517 NP isolates from healthy children . RESULTS: In archival isolates, tolerance to vancomycin was detected in 3.7% of NP and 10.6% of invasive isolates . Patients with meningitis caused by tolerant isolates had a worse estimated 30-day survival than did patients with meningitis caused by nontolerant isolates (49% vs . 86%; P = .048); 62.5% of tolerant archival NP isolates harbored a specific sequence change for pep27 and vex2 (P = .021) . Prospective analysis of 517 carriage isolates indicated that 8.1% were tolerant to vancomycin and that 82.1% of tolerant isolates harbored the specified marker gene sequences (P = .001) . CONCLUSIONS: Tolerance to vancomycin exists in the population of pneumococci . Tolerant isolates are associated with meningitis of increased mortality, and these isolates can be tracked by specific marker sequences in 2 genes .

J Infect Dis, 2004 Oct 15, 190(8), 1472 - 5 Epub 2004 Sep 08.
Effect of low-level resistance on subsequent enrichment of fluoroquinolone-resistant Streptococcus pneumoniae in rabbits; Etienne M et al.; BACKGROUND: We measured the effect of low-level fluoroquinolone resistance in Streptococcus pneumoniae on the development of high-level resistance within the context of the mutant selection window . METHODS: Rabbits infected with S . pneumoniae were treated with ciprofloxacin or moxifloxacin concentrations that simulated pharmacokinetics in treated humans; bacteria obtained from lungs were examined for fluoroquinolone susceptibility . RESULTS: Ciprofloxacin enriched resistant mutants from a wild-type strain; moxifloxacin did not . However, moxifloxacin enriched resistant mutants from a parC mutant; the drug concentration at the top of the selection window was determined . CONCLUSIONS: A parC resistance mutation facilitates the enrichment of high-level resistance, as was predicted by in vitro measurements .

J Neuropsychiatry Clin Neurosci, 2004 Summer, 16(3), 252 - 60
A possible association of recurrent streptococcal infections and acute onset of obsessive-compulsive disorder; Kim SW et al.; Rheumatic fever is an immunologically mediated disease that follows infection by group A beta-hemolytic Streptococcus (GABHS) . In rheumatic fever, antibodies generated against GABHS cross-react with the heart, joints, skin, and other sites, inducing an inflammatory, multisystem disease . Brain tissue-specific antibodies have been demonstrated in a subset of children with Sydenham chorea (a component of the Jones criteria for the diagnosis of rheumatic fever), and most Sydenham chorea patients manifest obsessive-compulsive symptoms very similar to those in traditional obsessive-compulsive disorder . The parallels drawn from the paradigm of Sydenham's chorea to Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is an area of active controversy . Newly emerging information on the role of GABHS superantigens in the pathogenesis of rheumatic fever is of particular interest . In this article, we review the microbial characteristics of GABHS and the subsequent immune responses to GABHS as a possible etiology of PANDAS.

J Dairy Sci, 2004 Oct, 87(10), 3561 - 73
Guidelines for monitoring bulk tank milk somatic cell and bacterial counts; Jayarao BM et al.; This study was conducted to establish guidelines for monitoring bulk tank milk somatic cell count and bacterial counts, and to understand the relationship between different bacterial groups that occur in bulk tank milk . One hundred twenty-six dairy farms in 14 counties of Pennsylvania participated, each providing one bulk tank milk sample every 15 d for 2 mo . The 4 bulk tank milk samples from each farm were examined for bulk tank somatic cell count and bacterial counts including standard plate count, preliminary incubation count, laboratory pasteurization count, coagulase-negative staphylococcal count, environmental streptococcal count, coliform count, and gram-negative noncoliform count . The milk samples were also examined for presence of Staphylococcus aureus, Streptococcus agalactiae, and Mycoplasma . The bacterial counts of 4 bulk tank milk samples examined over an 8-wk period were averaged and expressed as mean bacterial count per milliliter . The study revealed that an increase in the frequency of isolation of Staphylococcus aureus and Streptococcus agalactiae was significantly associated with an increased bulk tank somatic cell count . Paired correlation analysis showed that there was low correlation between different bacterial counts . Bulk tank milk with low (<5000 cfu/mL) standard plate count also had a significantly low level of mean bulk tank somatic cell count (<200,000 cells/mL), preliminary incubation count (<10,000 cfu/mL), laboratory pasteurization count (<100 cfu/mL), coagulase-negative staphylococci and environmental streptococcal counts (<500 cfu/mL), and noncoliform count (<200 cfu/mL) . Coliform count was less likely to be associated with somatic cell or other bacterial counts . Herd size and farm management practices had considerable influence on somatic cell and bacterial counts in bulk tank milk . Dairy herds that used automatic milking detachers, sand as bedding material, dip cups for teat dipping instead of spraying, and practiced pre-and postdipping had significantly lower bulk tank somatic cell and/or bacterial counts . In conclusion, categorized bulk tank somatic cell and bacterial counts could serve as indicators and facilitate monitoring of herd udder health and milk quality.

J Dairy Sci, 2004 Oct, 87(10), 3358 - 74
Effect of pathogen-specific clinical mastitis on milk yield in dairy cows; Grohn YT et al.; Our objective was to estimate the effects of the first occurrence of pathogen-specific clinical mastitis (CM) on milk yield in 3071 dairy cows in 2 New York State farms . The pathogens studied were Streptococcus spp.,Staphylococcus aureus, Staphylococcus spp., Escherichia coli, Klebsiella spp., Arcanobacterium pyogenes, other pathogens grouped together, and "no pathogen isolated." Data were collected from October 1999 to July 2001 . Milk samples were collected from cows showing signs of CM and were sent to the Quality Milk Production Services laboratory at Cornell University for microbiological culture . The SAS statistical procedure PROC MIXED, with an autoregressive covariance structure, was used to quantify the effect of CM and several other control variables (herd, calving season, parity, month of lactation, J-5 vaccination status, and other diseases) on weekly milk yield . Separate models were fitted for primipara and multipara, because of the different shapes of their lactation curves . To observe effects of mastitis, milk weights were divided into several periods both pre- and postdiagnosis, according to when they were measured in relation to disease occurrence . Another category contained cows without the type of CM being modeled . Because all pathogens were modeled simultaneously, a control cow was one without CM . Among primipara, Staph . aureus, E . coli, Klebsiella spp., and "no pathogen isolated" caused the greatest losses . Milk yield generally began to drop 1 or 2 wk before diagnosis; the greatest loss occurred immediately following diagnosis . Mastitic cows often never recovered their potential yield . Among older cows, Streptococcus spp., Staph . aureus, A . pyogenes, E . coli, and Klebsiella spp . caused the most significant losses . Many multipara that developed CM were actually higher producers before diagnosis than their nonmastitic herd-mates . As in primipara, milk yield in multipara often began to decline shortly before diagnosis; the greatest loss occurred immediately following diagnosis . Milk loss persisted until at least 70 d after diagnosis for Streptococcus spp., Klebsiella spp., and A . pyogenes . The tendency for higher producing cows to contract CM may mask its impact on cow health and production . These findings provide dairy producers with more information on which pathogen-specific CM cases should receive treatment and how to manage these cows, thereby reducing CM impact on cow well being and profitability.

J Dairy Sci, 2004 Oct, 87(10), 3322 - 9
Extended ceftiofur therapy for treatment of experimentally-induced Streptococcus uberis mastitis in lactating dairy cattle; Oliver SP et al.; Streptococcus uberis is an important cause of mastitis in dairy cows throughout the world, particularly during the dry period, the period around calving, and during early lactation . Strategies for controlling Strep . uberis mastitis are poorly defined and are currently inadequate . Objectives of the present study were to evaluate efficacy of ceftiofur, a new broad-spectrum cephalosporin antibiotic, for treatment of experimentally induced Strep . uberis intramammary infections (IMI) in lactating dairy cows during early lactation and to determine whether extended therapy regimens enhanced efficacy of ceftiofur . Efficacy of extended ceftiofur intramammary therapy regimens was investigated in 37 mammary quarters of 23 dairy cows that developed clinical mastitis following experimental infection with Strep . uberis during early lactation . Cows that developed clinical mastitis during the challenge period were allocated randomly to 3 groups representing 3 different ceftiofur treatment regimens: 2-d (n = 7 mammary quarters), 5-d (n = 16 mammary quarters), and 8-d (n = 14 mammary quarters) treatment regimens . For all groups, 125 mg of ceftiofur hydrochloride was administered via intramammary infusion . A bacteriological cure was defined as an experimentally infected quarter that was treated and was bacteriologically negative for the presence of Strep . uberis at 7, 14, 21, and 28 d posttreatment . Percentage of Strep . uberis IMI eliminated was 43, 88, and 100% for the 2-, 5-, and 8-d ceftiofur treatment regimens, respectively . Both the 5- and 8-d ceftiofur extended therapy treatment regimens had significantly higher bacterial cure rates than the standard 2-d ceftiofur treatment regimen . The bacterial cure rate of the 8-d ceftiofur extended therapy group was marginally better (P = 0.052) than the 5-d ceftiofur extended therapy group . Results of this study indicate that ceftiofur therapy was effective for eliminating Strep . uberis experimental IMI, and 5- and 8-d extended ceftiofur therapy regimens were more effective than the standard 2-d treatment.

J Bacteriol, 2004 Oct, 186(19), 6383 - 90
Adaptive acid tolerance response of Streptococcus sobrinus; Nascimento MM et al.; Streptococcus mutans and Streptococcus sobrinus are the bacteria most commonly associated with human dental caries . A major virulence attribute of these and other cariogenic bacteria is acid tolerance . The acid tolerance mechanisms of S . mutans have begun to be investigated in detail, including the adaptive acid tolerance response (ATR), but this is not the case for S . sobrinus . An analysis of the ATR of two S . sobrinus strains was conducted with cells grown to steady state in continuous chemostat cultures . Compared with cells grown at neutral pH, S . sobrinus cells grown at pH 5.0 showed an increased resistance to acid killing and were able to drive down the pH through glycolysis to lower values . Unlike what is found for S . mutans, the enhanced acid tolerance and glycolytic capacities of acid-adapted S . sobrinus were not due to increased F-ATPase activities . Interestingly though, S . sobrinus cells grown at pH 5.0 had twofold more glucose phosphoenolpyruvate:sugar phosphotransferase system (PTS) activity than cells grown at pH 7.0 . In contrast, glucose PTS activity was actually higher in S . mutans grown at pH 7.0 than in cells grown at pH 5.0 . Silver staining of two-dimensional gels of whole-cell lysates of S . sobrinus 6715 revealed that at least 9 proteins were up-regulated and 22 proteins were down-regulated in pH 5.0-grown cells compared with cells grown at pH 7.0 . Our results demonstrate that S . sobrinus is capable of mounting an ATR but that there are critical differences between the mechanisms of acid adaptation used by S . sobrinus and S . mutans.

J Dairy Sci, 2004 Sep, 87(9), 3089 - 91
Efficacy of a 0.1% iodine teat dip against Staphylococcus aureus and Streptococcus agalactiae during experimental challenge; Boddie RL et al.; An experimental challenge trial was performed according to the guidelines recommended by the National Mastitis Council (NMC) . A 0.1% iodine teat dip (Quartermate with I-Tech) was examined . This product gave an 87.9% reduction of new intramammary infections with Staphylococcus aureus and a 66.5% reduction for Streptococcus agalactiae compared with a negative control . Teat end and teat skin characteristics remained excellent throughout the trial.

Clin Exp Immunol, 2004 Oct, 138(1), 83 - 93
Peripheral blood T cell responses to keratin peptides that share sequences with streptococcal M proteins are largely restricted to skin-homing CD8(+) T cells; Johnston A et al.; The association of psoriasis with Streptococcus pyogenes throat infections suggests a potential antigenic target for the T cells that are known to infiltrate psoriatic skin . Streptococcal M protein share an extensive sequence homology with the human epidermal keratins . Keratin 17 (K17), while being mostly absent from uninvolved skin, is up-regulated in psoriatic lesions . Consequentially, M-protein-primed T cells may recognize up-regulated keratin epitopes via molecular mimicry . Using in vitro lymphocyte culture and cytokine flow cytometry we demonstrate that HLA-Cw*0602(+) psoriasis patients had significant CD8(+) T cell interferon (IFN)-gamma responses to peptides from the K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding . These responses were about 10 times more frequent in the skin-homing cutaneous lymphocyte-associated antigen-expressing (CLA(+)) subset of CD8(+) T cells . CD4(+) T cells showed only borderline responses . CLA(+) CD8(+) T cells from Cw6(+) non-psoriatic individuals responded to some M6 peptides but rarely to K17 peptides . Cw6(-) psoriasis patients showed a response that was intermediate between Cw6(+) patients and controls . These findings indicate that psoriatic individuals have CD8(+) T cells that recognize keratin self-antigens and that epitopes shared by streptococcal M proteins and human keratins may be targets for the CD8(+) T cells that infiltrate psoriatic skin lesions.

Am J Reprod Immunol, 2004 Sep, 52(3), 197 - 203
Effect of peptidoglycan-polysaccharide complex on reproductive efficiency in sheep; Holaskova I et al.; PROBLEM: Spontaneous mastitis or induced infections mimicking mastitis reduce pregnancy rates in ruminants . The effect of immunization with either a mastitis-related pathogen component, peptidoglycan-polysaccharide (PG-PS), or killed Streptococcus pyogenes on pregnancy outcome was investigated . METHOD OF STUDY: Ewe lambs were immunized with PG-PS (n = 50) or killed bacteria (n = 50) or were not immunized (control, n = 100) . Titers of PG-PS immunoglobulin G (IgG) were detected by enzyme-linked immunosorbent assay (ELISA) . Ewes were bred by rams at synchronized estrus . All immunized ewes and half of the ewes not immunized were challenged with PG-PS on day 5 after breeding . Pregnancy maintenance was evaluated . RESULTS: Although the proportion of ewes pregnant at day 42 after breeding did not differ among treatments, the probability of pregnancy decreased with total dose of PG-PS (P < 0.05) . CONCLUSIONS: Immunization of ewe lambs with PG-PS or killed S . pyogenes did not improve pregnancy maintenance . Furthermore, the toxic streptococcal component decreased pregnancy rate in immunized sheep in a dose-dependent manner.

MMW Fortschr Med, 2004 May 20, 146(21), 43 - 5
{Community-acquired pneumonia--treatment perspectives in the physician's office}; Ewig S; In patients with a focal finding on auscultation, a chest radiograph should be performed to confirm pneumonia . The need for hospitalization can be supported objectively with the aid of the Pulmonary Severity Index (PSI) or the CURB score . The most common pathogen of pneumonia is Streptococcus pneumoniae . The choice of appropriate antimicrobial therapy is based on the expected spectrum of pathogens, severity, the risk profile and the patient's history of antimicrobial substance use . In this connection, the progressive development of resistance forbids first-choice recommendations, and "cycling" should be attempted instead . Depending on the regional resistance situation and prior conditions, amoxicillin in combination with a beta-lactamase inhibitor, doxycycline, a macrolide or a ketolide may be considered for treatment purposes . For higher levels of severity, fluorquinolones also have proven value.

Int J Clin Pract, 2004 Aug, 58(8), 769 - 76
Therapeutic implications of macrolide resistance in pneumococcal community-acquired lower respiratory tract infections; Marrie TJ; Macrolide anti-bacterials are widely used for the empirical treatment of lower respiratory tract infections (RTIs) due to their activity against Streptococcus pneumoniae and other common respiratory pathogens and good safety/tolerability profile . However, the prevalence of macrolide resistance, particularly pneumococcal macrolide resistance, is increasing all around the world . The mechanisms underlying macrolide resistance include efflux pump, methylase activity and, less commonly, ribosomal mutation, which produce differing levels of resistance . Growth in macrolide resistance has been linked to the increased use of these agents, and several risk factors for the development of resistance have been identified . There are emerging data to suggest that in vitro macrolide resistance may increase the likelihood of treatment failure in patients with lower RTIs . However, at present, treatment failure is rare and randomised; intervention-based trials investigating the impact of anti-bacterial resistance on clinical outcomes are lacking . Strategies to promote appropriate use of macrolides and other anti-bacterials are needed, both to maximise therapeutic impact and to minimise the development of resistance . Furthermore, there is a need for alternative anti-bacterial agents which have high efficacy against respiratory pathogens (including resistant strains) and a low potential to induce resistance.

Int J Clin Pract, 2004 Aug, 58(8), 735 - 9
Maternal colonisation with group B streptococcus and effectiveness of a culture-based protocol to prevent early-onset neonatal sepsis; Yucesoy G et al.; This study was conducted to find out the group B streptococcus colonisation of pregnant women in Kocaeli, Turkey . A culture plus individualised high-risk-based antibiotic prophylaxis was compared with high-risk-based approach alone . The screening of women was performed via vaginal and anal cultures for group B streptococcus (GBS) . The maternal GBS colonisation rate was found to be 6.5% . All colonised women or preterm labours with unavailable culture results until delivery received prophylactic antibiotics . Neonatal colonisation rate and early-onset neonatal sepsis due to GBS was 1/200 . The unscreened 900 women received prophylactic antibiotics due to a risk factor-based approach . The neonatal colonisation rate was 17/900 (p = 0.1), and the rate of early-onset neonatal sepsis was 3/900 (p = 0.6) . A culture plus individualised high-risk-based antibiotic prophylaxis provided an insignificant change in neonatal colonisation and early-onset neonatal sepsis with GBS when compared with high-risk-based approach alone.

Scand J Infect Dis, 2004, 36(9), 629 - 35
The impact of active intervention on the spread of penicillin-resistant Streptococcus pneumoniae in Swedish day-care centres; Hogberg L et al.; Policies for handling cases of penicillin-non-susceptible Streptococcus pneumoniae (PNSP) in day-care groups vary between different counties in Sweden . The aim of this study was to evaluate the epidemiological effect of excluding PNSP-carriers from children's day-care centres (DCC) . We followed the incidence in 14 DCC groups with ongoing PNSP-spread, by repeated group screens until no further cases could be identified . All identified carriers were excluded from DCC attendance in study area A (Skane region) while they remained in the group in study area B (Goteborg and orebro), according to local policies . The intervention effect was evaluated by comparing the number of additional cases after the baseline screen (start of the intervention period) between the 2 study areas . All PNSP-isolates were characterized by resistance pattern, serotype and pulse-field gel electrophoresis . The relative risk for children in DCCs without active intervention was 6.4 (95% CI: 2.0-20.7) . Each prevented case in area A can be estimated to have demanded the exclusion of 2 other children from day care for approximately 4 weeks each . The total cost-benefit outcome of this action has to be seen in the light of the local situation with regard to the population prevalence and the distribution of other risk factors.

Acta Otolaryngol, 2004 Sep, 124(7), 863 - 6
Transoral approach to drain streptococcus pneumoniae spinal epidural abscess in an HIV-infected adult; Benitez P et al.; Spinal epidural abscess due to Streptococcus pneumoniae is extremely rare in adults . It typically occurs in the thoracic, lumbar or lumbosacral epidural spaces, and less frequently in the cervical epidural space . The principal causative microbial agent is Staphylococcus aureus, representing 70% of cases, while 1.6% of cases are caused by S . pneumoniae . We report the first case of an HIV-infected patient with a cervical spinal epidural abscess . The patient was a 43-year-old male with pneumococcal bacteremia and a metatarsal abscess . He reported cervical pain with muscle spasm during cephalic flexion and extension, fever and a painful tumefaction on the second metatarsal of the left foot . MRI confirmed that the retropharyngeal abscess extended to the cervical spinal epidural space . Antibiotic therapy with cefotaxime plus vancomycin was initiated and a transoral surgical approach was used to achieve retropharyngeal and local debridement of the metatarsal abscess . Blood and pus cultures were positive for S . pneumoniae . After 4 months of follow-up the patient remained asymptomatic, without clinical or MRI evidence of recurrence.

Acta Otolaryngol, 2004 Sep, 124(7), 794 - 7
Depletion of mucosal substance P in acute otitis media; Caye-Thomasen P et al.; OBJECTIVE: The neuropeptide substance P (SP) is an inducer of neurogenic inflammation and bone resorption in the middle ear . Resorption of the bone tissue structures surrounding the middle ear cavity is a distinct feature of the initial stage of acute otitis media (AOM), which may be due to nerve fiber release of SP . MATERIAL AND METHODS: To investigate possible release of SP in the middle ear mucosa during AOM, we used a well-established rat model of AOM caused by Streptococcus pneumoniae . Following tissue extraction on Days 1, 3 and 6 post-inoculation, the mucosal concentration of SP was measured using a radioimmunoassay . RESULTS: Compared to sham-inoculated control ears, the concentration of SP was significantly reduced on Day 1 and even further reduced on Day 3, whereas partial replenishment was found on Day 6 . CONCLUSION: SP seems to be depleted in the rat middle ear mucosa in the hyperacute phase of AOM . This depletion is followed by replenishment and the concentration of SP approaches its normal level 6 days post-inoculation . The release of SP may be the trigger of the concurrent bone resorption and may further augment the inflammatory response to the bacterial colonization.

J Matern Fetal Neonatal Med, 2004 Jul, 16(1), 67 - 8
Hydrocephalus secondary to group B streptococcal meningitis; Srinivasan L et al.; Group B hemolytic streptococcus (GBS) is the most common cause of neonatal sepsis and meningitis . However, hydrocephalus as a presentation of neonatal GBS meningitis has not been reported . We report herein the case of a 23-day-old male infant who presented with significant hydrocephalus and subtle seizures, without a febrile episode, due to GBS meningitis . The infant needed a 3-week course of antibiotics, a ventriculoperitoneal shunt and anticonvulsant therapy.

Clin Chim Acta, 2004 Oct, 348(1-2), 1 - 8
Antibodies to oxidized LDL in atherosclerosis development--clinical and animal studies; Hulthe J; Atherosclerotic lesions represent the principal cause of death in western industrialized countries . Immune mechanisms have been suggested to play a key role in the development of atherosclerosis . Several lines of evidence support that oxidized LDL (oxLDL) may be a key antigen in atherosclerosis . Antibodies to oxLDL have been found in human and rabbit plasma and in atherosclerotic lesions . So far, it has not been well established if the immune response is predominantly pro- or antiatherogenic . During the last decade, numerous studies have been performed investigating the relationship between circulating antibodies in plasma in relation to endothelial dysfunction, subclinical atherosclerosis and cardiovascular events in different patient categories . Taken together, these studies have shown diverging results . However, most studies have shown that elevated IgG titers to oxLDL are related to atherosclerotic disease . Even if fewer studies have investigated IgM titers, most studies seem to show an inverse relationship between IgM titers and atherosclerotic disease . In animal studies, it has been shown that immunization with oxLDL induces antibody formation (both IgG and IgM) and protects against atherosclerosis development . Furthermore, it has also been shown that immunization with Streptococcus pneumoniae induce an IgM response, which is associated with decreased atherosclerosis development, and plasma from these mice also has the ability to block uptake of oxLDL to macrophages . To conclude, antibodies to oxLDL in clinical cardiovascular disease show diverging results, while animal studies suggest that immunization may have a beneficial role in atherosclerosis development . Prospective and intervention studies, as well as mechanistic studies are clearly needed to elucidate the possible causal role of antibodies to oxLDL in man.

Vet Rec, 2004 Aug 14, 155(7), 201 - 4
Rupture of the flexor tendons of a horse secondary to a non-responsive digital sheath sepsis; Kidd JA et al.; A 12-year-old hunter gelding became severely lame as a result of a laceration to the sheath of the digital flexor tendons of its left hindlimb, but there was no apparent damage to the tendons . The injury became chronically infected with Pseudomonas and Streptococcus species and Escherichia coli which did not respond to antibiotic treatment, and the horse remained lame . A postmortem examination revealed that the tendons had ruptured.

Eur J Immunol, 2004 Oct, 34(10), 2843 - 53
Primary induction of CD4 T cell responses in nasal associated lymphoid tissue during group A streptococcal infection; Park HS et al.; CD4 T cells are important for development of long-term immunity to bacterial infections . Here we describe construction of a group A streptococcus (GAS) strain that expresses the model ovalbumin epitope (OVA) on its surface, and the use of this strain in adoptive transfer experiments to study CD4 T cell response to bacterial infection in nasal-associated lymphoid tissue (NALT), which was previously shown to be a specific target for GAS colonization . The OVA(+) GAS, but not the wild-type strain was shown to activate CD4 T cells in an antigen-specific manner both in vitro and in vivo . After intranasal infection of mice with this strain, OVA-specific CD4 T cells were first activated in NALT, which is functionally equivalent to human tonsils, rather than in the cervical lymph nodes . During localized infection, OVA(+) GAS induced rapid and prolonged activation of CD4 T cells at higher magnitudes in the NALT than in draining lymph nodes and spleen, where CD4 T cells underwent little or no activation . In contrast, systemic infection induced significantly higher activation of CD4 T cells in both lymph nodes and spleens, compared to when the infection was localized in NALT . Further investigation of cellular immune responses in NALT during GAS infection using adoptive T cell transfer, combined with the model antigen on the pathogen may ultimately shed light on mechanisms for failure of children to develop protective immune responses following streptococcal tonsillitis.

J Paediatr Child Health, 2004 Sep-Oct, 40(9-10), 530 - 3
Dental caries and salivary immunoglobulin A in Down syndrome children; Lee SR et al.; OBJECTIVES: This study investigated the relationship between dental caries and the salivary Streptococcus mutans specific antibodies in Down syndrome children . METHODS: Nineteen children with Down syndrome and 41 normal children aged 8-17 years were selected . The oral health status (dental caries experience, pit and fissure depth, dental arch space, and Simplified Oral Hygiene Index) was examined and unstimulated saliva was collected . The total salivary immunoglobulin A (IgA) and S . mutans specific salivary IgA concentrations were measured using ELISA . RESULTS: The decayed and filled surface index of the deciduous teeth, and the decayed, missing, and filled surfaces index of the permanent teeth in Down syndrome children were significantly lower compared to those in normal children . The salivary S . mutans (serotype g and c) specific IgA concentrations were significantly higher in Down syndrome children than in the normal children . There was no significant difference in the tooth characteristics and oral hygiene between the two groups . CONCLUSIONS: The low caries prevalence in Down syndrome children appears to be due to immune protection caused by the elevated salivary S . mutans specific IgA concentrations.

J Vet Sci, 2004 Sep, 5(3), 263 - 5
Persistent occurrence of a single Streptococcus equi subsp . zooepidemicus clone in the pig and monkey population in Indonesia; Salasia SI et al.; In the present study 41 mucoid growing Streptococcus equi subsp . zooepidemicus strains (37 strains isolated from healthy two from diseased pigs, two strains isolated from healthy monkeys) appeared to be phenotypically and genotypically identical to mucoid growing S . equi subsp . zooepidemicus strains isolated from a previously described outbreak among the pig and monkey population on the island of Bali, Indonesia . These findings indicate that the mucoid growing S . equi subsp . zooepidemicus clone was still present in the pig and monkey population in Indonesia.

J Clin Microbiol, 2004 Sep, 42(9), 4396 - 8
Streptococcus porcinus as a cause of spontaneous preterm human stillbirth; Martin C et al.; We report, to our knowledge, on the first case of a woman suffering stillbirth due to Streptococcus porcinus on the basis of microbiologic and histologic data.

J Clin Microbiol, 2004 Sep, 42(9), 4383 - 5
Pyelonephritis and urosepsis caused by Streptococcus pneumoniae; Dufke S et al.; This report presents the case of a patient with a massive pyelonephritis and a urosepsis caused by Streptococcus pneumoniae . This case is unusual as the focus was distant from the respiratory tract, the usual primary site of infection caused by this organism . No other primary site of infection was documented.

J Clin Microbiol, 2004 Sep, 42(9), 4323 - 6
Antimicrobial susceptibilities of invasive pediatric Abiotrophia and Granulicatella isolates; Zheng X et al.; Abiotrophia and Granulicatella species have been associated with various infections . Antimicrobial susceptibility data for these nutritionally variant streptococcus-like organisms, especially for pediatric isolates, are very limited . Little is known about the genetic bases of their resistance mechanisms . We report the results of identification to bacterial species level, antimicrobial susceptibility testing, macrolide resistance testing, and detection of genes encoding that resistance for a collection of 15 pediatric clinical isolates from normally sterile sites . Our results indicate that the prevalence of beta-lactam and macrolide resistance is high and that both erm and mef are found in these isolates.

J Clin Microbiol, 2004 Sep, 42(9), 4214 - 22
Phenotypic and molecular characteristics of Streptococcus agalactiae isolates recovered from milk of dairy cows in Brazil; Duarte RS et al.; Information on the characteristics of Streptococcus agalactiae obtained from bovine sources in Brazil is still very limited . The aim of this study was to assess the phenotypic and genotypic diversity among S . agalactiae isolates from milk of dairy cows presenting clinical or subclinical mastitis in the southeast region of Brazil . Phenotypic characterization was based on physiological and serological tests . Antimicrobial susceptibility tests were carried out by the disk method . Genetic diversity was evaluated by using random amplified polymorphic DNA-PCR (RAPD-PCR) (by using the primer 1254) and pulsed-field gel electrophoresis (PFGE) (by using SmaI as the restriction enzyme) and by PCRs for detection of genes associated with resistance to erythromycin and tetracycline as well as PCRs for detection of genes coding for cell surface-associated proteins . According to the results of physiologic tests, 45 (52.9%) isolates showed beta-hemolysis and 44 (51.7%) were susceptible to bacitracin . Fourteen different biotypes were detected . The two most frequent biotypes comprised strains that were non-beta-hemolytic; fermented galactose, lactose, and salicin; produced protease; and were negative for DNase production . Serotype III was predominant (66 isolates {77.6%}), followed by serotypes II, Ia, Ib, and VI . Resistance to tetracycline and erythromycin was found in 38 (44.7%) and 9 (10.5%) isolates, respectively, with tet(O) (31.7%) and erm(B) (100%) being the most frequently occurring resistance genes . Three genes coding for surface proteins, bca, lmb, and scpB, were detected in 55 (64.7%), 7 (8.2%), and 43 (50.5%) isolates, respectively . In most cases, isolates from animals in the same herd presented closely related genetic profiles (determined by either RAPD-PCR or PFGE), which were distinct from those of isolates from different herds.

J Clin Microbiol, 2004 Sep, 42(9), 3998 - 4006
Epidemiology and molecular characterization of Streptococcus pyogenes recovered from scarlet fever patients in central Taiwan from 1996 to 1999; Chiou CS et al.; One hundred seventy-nine Streptococcus pyogenes isolates recovered from scarlet fever patients from 1996 to 1999 in central Taiwan were characterized by emm, Vir, and pulsed-field gel electrophoresis (PFGE) typing methods . The protocols for Vir and PFGE typing were standardized . A database of the DNA fingerprints for the isolates was established . Nine emm or emm-like genes, 19 Vir patterns, and 26 SmaI PFGE patterns were detected among the isolates . Among the three typing methods, PFGE was the most discriminatory . However, it could not completely replace Vir typing because some isolates with identical PFGE patterns could be further differentiated into several Vir patterns . The prevalent emm types were emm4 (n = 81 isolates {45%}), emm12 (n = 64 {36%}), emm1 (n = 14 {8%}), and emm22 (n = 13 {7%}) . Some emm type isolates could be further differentiated into several emm-Vir-PFGE genotypes; however, only one genotype in each emm group was usually predominant . DNA from nine isolates was resistant to SmaI digestion . Further PFGE analysis with SgrAI showed that the SmaI digestion-resistant strains could be derived from indigenous strains by horizontal transfer of exogenous genetic material . The emergence of the new strains could have resulted in an increase in scarlet fever cases in central Taiwan since 2000 . The emm sequences, Vir, and PFGE pattern database will serve as a basis for information for the long-term evolutionary study of local S . pyogenes strains.

Arch Intern Med, 2004 Sep 13, 164(16), 1807 - 11
Assessment of the usefulness of sputum culture for diagnosis of community-acquired pneumonia using the PORT predictive scoring system; Garcia-Vazquez E et al.; BACKGROUND: The usefulness of sputum culture in guiding microbiological diagnosis of community-acquired pneumonia is controversial . We evaluate and assess it using the Patients Outcome Research Team (PORT) predictive scoring system . METHODS: A cohort of 1669 patients with community-acquired pneumonia was studied . Before administering antibiotic therapy, sputum was collected and its quality evaluated . Samples were gram stained and those of good quality were assessed for a predominant morphotype (PM) . Sputum cultures were processed according to standard protocols . RESULTS: A sputum sample was obtained from 983 (59%) of the 1669 patients and 532 (54%) of the samples were of good quality . There was a PM in 240 (45%) of the latter samples (ie, for 14.4% of the 1669 patients) and there was no PM in 292 (55%) . Culture yielded a microorganism in 207 (86%) of the 240 samples with PM and 57 (19.5%) of the 292 samples without PM (P<.05) . Rates of sputum obtained, good-quality sputum specimens, PM identification, and positive culture were not significantly different among the PORT-score groups of patients (P>.05) . The sensitivity and specificity of the gram-positive diplococci identification in the sputum culture of Streptococcus pneumoniae were 60% and 97.6%, and the positive and negative predictive values were 91% and 85.3%, respectively . CONCLUSIONS: Good-quality sputum with PM could be obtained in only 14.4% of all patients . A PORT-score group in which sputum could be of greater usefulness in identifying the causative organism could not be identified . The presence of gram-positive diplococci in gram-stained sputum culture was highly specific for S pneumoniae.

Vaccine, 2004 Sep 28, 22(29-30), 3890 - 6
Typing of pneumococcal surface protein A (PspA) in Streptococcus pneumoniae isolated during epidemiological surveillance in Brazil: towards novel pneumococcal protein vaccines; Brandileone MC et al.; Pneumococcal protein vaccine based on pneumococcal surface protein A (PspA) is in development with the potential to offer broad range of protection against different strains . We have investigated the frequency of PspA family 1 (Fam1) and family 2 (Fam2) proteins among Streptococcus pneumoniae recovered from ongoing surveillance in Brazil . Fam1 and Fam2 were expressed in comparable rates among 366 isolates, with the potential coverage of 94.3% . PspA families were not associated to age group or source of isolates . However, considering the significant tendency of increasing prevalence of Fam2 associated to widespread dissemination of the genetically-related resistant strains, the monitoring of the PspA families derived from population-based data may be necessary in the context of vaccine development.

Am J Med, 2004 Aug 2, 117 Suppl 3A, 16S - 22S
Overview of newer antimicrobial formulations for overcoming pneumococcal resistance; Craig WA; The pharmacokinetic (PK) and pharmacodynamic (PD) profile of an antimicrobial agent provides important information that can be used to maximize bacteriologic and clinical efficacy, minimize selective pressure for the development of antimicrobial resistance, and determine an optimal dosing regimen . Judicious selection of an antimicrobial based on local susceptibility data and PK and PD parameters is imperative in this era of increasing resistance among Streptococcus pneumoniae, a leading cause of community-acquired respiratory tract infections . The beta-lactam antimicrobials display time-dependent bacterial killing with minimal to no persistent effects . Ketolides and fluoroquinolones display concentration-dependent bacterial killing, and tetracyclines and macrolides display time-dependent killing . All have prolonged persistent effects (e.g., postantibiotic effect) that retard or prevent bacterial regrowth when free drug levels fall below the minimum inhibitory concentration (MIC) . New high-dose and/or extended-release formulations of traditional antimicrobials have been added to the current armamentarium for treatment of community-acquired respiratory tract infections . These formulations include amoxicillin-clavulanate potassium powder for oral suspension 90/6.4 mg/kg per day divided every 12 hours (Augmentin ES-600; GlaxoSmithKline, Research Triangle Park, NC), amoxicillin-clavulanate potassium extended-release tablets 2 x 1,000 mg/62.5 mg every 12 hours (Augmentin XR; GlaxoSmithKline), clarithromycin extended-release tablets 2 x 500 mg once daily (Biaxin XL; Abbott Laboratories, North Chicago, IL), and cefaclor extended-release tablets 375 mg or 500 mg every 12 hours (Ceclor CD; Eli Lilly Pharmaceuticals, Indianapolis, IN) . Of these agents, only amoxicillin-clavulanate potassium powder for oral suspension and amoxicillin-clavulanate potassium extended-release tablets were designed to treat infections caused by penicillin-resistant pneumococci (penicillin MIC < or =2 microg/mL) . Extended-release clarithromycin does not provide higher daily doses than its immediate-release counterpart; rather, it allows for once-daily dosing of this agent because of its slower absorption following oral administration . Extended-release cefaclor is considered clinically equivalent to 250 mg of immediate-release cefaclor pulvules administered 3 times daily; it cannot be used interchangeably with 500 mg 3-times-daily dosages of other cefaclor formulations . Thus, despite providing a similar or higher total daily dose than its immediate-release counterpart, extended-release cefaclor is indicated only for the treatment of patients with mild to moderate infections caused by susceptible strains of certain organisms.

Am J Med, 2004 Aug 2, 117 Suppl 3A, 3S - 15S
Streptococcus pneumoniae: epidemiology and patterns of resistance; Jacobs MR; Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis, otitis media, and sinusitis; it results in significant morbidity and mortality in patients with pneumonia and meningitis . The pneumococcus is a common colonizing bacterium in the respiratory tract; it is especially common in the respiratory tracts of children, where it is frequently exposed to antimicrobial agents . This exposure can lead to resistance . Penicillin nonsusceptibility is found in nearly 40% of strains causing disease in adults, although often these cases are treatable with appropriate dosing regimens of many oral and parenteral beta-lactam agents . In the United States resistance to macrolides is widespread--averaging approximately 28%--but geographically variable, ranging from 23% in the northwest to 30% in the northeast . Resistance to tetracyclines and trimethoprim-sulfamethoxazole are reported in approximately 20% and 35% of isolates, respectively, and resistance to multiple classes of agents is increasingly common . Amoxicillin, amoxicillin-clavulanate, respiratory fluoroquinolones, and clindamycin are currently the most effective agents for treatment of respiratory tract infections caused by S pneumoniae, with >90% of isolates in the United States being susceptible . Vancomycin is the only agent against which resistance has not emerged . Patient groups that are at increased risk for developing resistant pneumococcal infections have been identified and include patients with malignancies, human immunodeficiency virus infection, and sickle-cell disease . Judicious use of antimicrobials is the key to preventing the emergence of further resistance, particularly as few new classes of agents are likely to become available for clinical use in the short term.

EMBO Rep, 2004 Oct, 5(10), 1000 - 6 Epub 2004 Sep 10.
Toll-like receptor 2-dependent bacterial sensing does not occur via peptidoglycan recognition; Travassos LH et al.; Toll-like receptor 2 (TLR2) has been shown to recognize several classes of pathogen-associated molecular patterns including peptidoglycan (PG) . However, studies linking PG with TLR2 recognition have relied mainly on the use of commercial Staphylococcus aureus PG and have not addressed TLR2 recognition of other PG types . Using highly purified PGs from eight bacteria (Escherichia coli, Pseudomonas aeruginosa, Yersinia pseudotuberculosis, Helicobacter pylori, Bacillus subtilis, Listeria monocytogenes, Streptococcus pneumoniae and S . aureus), we show that these PGs are not sensed through TLR2, TLR2/1 or TLR2/6 . PG sensing is lost after removal of lipoproteins or lipoteichoic acids (LTAs) from Gram-negative and Gram-positive cell walls, respectively . Accordingly, purified LTAs are sensed synergistically through TLR2/1 . Finally, we show that elicited peritoneal murine macrophages do not produce tumour necrosis factor-alpha or interleukin-6 in response to purified PGs, suggesting that PG detection is more likely to occur intracellularly (through Nod1/Nod2) rather than from the extracellular compartment.

J Chromatogr B Analyt Technol Biomed Life Sci, 2004 Oct 15, 810(1), 41 - 7
Detection of cariogenic bacterial genes by microchip electrophoresis; Karasawa K et al.; Allele-specific PCR primers were designed, based on the dextranase (dex) gene, to identify Streptococcus mutans and Streptococcus sobrinus in dental plaque; subsequently, PCR products were detected via microchip electrophoresis (ME) . In order to amplify the dex gene fragment of S . mutans and S . sobrinus, the following two PCR methods were established . Duplex allele-specific PCR primers were designed on a region of low DNA homology; furthermore, 211 and 126-bp fragments were amplified for S . mutans and S . sobrinus, respectively . Common PCR primer for single allele-specific PCR was designed so as to sandwich a region exhibiting high homology and amplify PCR product of different DNA size due to deletion of small DNA fragment in two dex genes . S . mutans and S . sobrinus were amplified, leading to the generation of 202 and 226-bp products, respectively . Analysis of DNA base size by ME in order to achieve efficient separation employed a polymer mixture consisting of hydroxypropyl methylcellulose (HPMC) and polyethylene oxide (PEO) . In the presence of a polymer mixture of 0.125% PEO/0.6% HPMC, two PCR products were obtained, displaying degree of separation of 226 bp/202 bp of 2.67 (Rs) . Reproducibility (CV%, n = 7) was 0.3%; additionally, separation time was approximately 85 s . This method was applied to the detection of S . mutans and S . sobrinus in dental plaque . Detection of the dex genes of S . mutans and S . sobrinus characterized by quickness, precision and high sensitivity was possible.

Biochem Biophys Res Commun, 2004 Aug 13, 321(1), 192 - 6
Expression and characterization of cholera toxin B-pneumococcal surface adhesin A fusion protein in Escherichia coli: ability of CTB-PsaA to induce humoral immune response in mice; Areas AP et al.; Cholera toxin B subunit (CTB) is responsible for CT holotoxin binding to the cell and has been described as a mucosal adjuvant for vaccines . In this work, the ctxB gene was genetically fused to the psaA gene from Streptococcus pneumoniae, a surface protein involved in its colonization in the host that is also considered a vaccine antigen candidate against this pathogen . The CTB-PsaA fusion protein was expressed in Escherichia coli, and the purified protein was used for intranasal immunization experiments in Balb/C mice . CTB-PsaA was able to induce both systemic and mucosal antibodies evaluated in serum, saliva, and in nasal and bronchial wash samples, showing that CTB-PsaA is a promising molecule to be investigated as S . pneumoniae vaccine antigen candidate.

Biochem Biophys Res Commun, 2004 Aug 20, 321(2), 472 - 8
Bacteriostatic properties of biomatrices against common orthopaedic pathogens; Carlson GA et al.; Tissue-engineered grafts for tissue regeneration include either mature or progenitor cells seeded onto biomatrices that provide shape and support for developing tissue . Popular biomaterials used in orthopaedic surgery include collagen type I, hyaluronic acid, hydroxyapatite, and polylactic polyglycolic acid (PLGA) . Biomatrices with bacteriostatic properties may be beneficial in promoting tissue-engineered graft survival in patients susceptible to infection . We evaluated the bacteriostatic effects of these biomaterials on the growth of the four most common orthopaedic bacterial pathogens: Staphylococcus aureus, Staphylococcus epidermidis, beta-hemolytic Streptococcus, and Pseudomonas aeruginosa . Hyaluronic acid demonstrated the largest bacteriostatic effect on these pathogens by inhibiting bacterial growth by an average of 76.8% (p = 0.0005) . Hydroxyapatite and collagen inhibited growth on average by 49.7% (p = 0.011) and 37.5% (p = 0.102), respectively . PLGA exhibited the least bacteriostasis with an average inhibition of 9.8% (NS) and actually accelerated the growth of beta-hemolytic Streptococcus and P . aeruginosa.

Ann Biol Clin (Paris), 2004 Sep-Oct, 62(5), 573 - 7
{Rapid diagnosis tests in group A beta-heamolytic streptococcal pharyngitis}; Chiadmi F et al.; OBJECTIVE: Routine clinical diagnosis of Streptococcus pyogenes in pharyngitis is not always easy . The use in common practice of rapid diagnosis test (RDT), might offer a best control of the antibiotic treatments . The aim of this study is to present seven rapid diagnosis tests, to assess their feasibility and finally to determine the bacteriological correlation . METHOD: We propose to compare the results obtained with seven RDT, and to assess their interest in medical diagnosis for group A streptococcus pharyngitis . A prospective study was conducted for three months, a RDT was performed for children (n=75) between eight and fourteen years old presenting acute pharyngitis . Several throat sampling were performed to order cultures . RESULTS: The group A streptococcus was isolated in 33% (n=25) of throat sampling . Comparing cultures results, and for all studied tests, we obtained comparable performances with manufacturer data, specificity upper than 94% and sensitivity upper than 88% . CONCLUSION: All assessed RDT may offer to physicians a decision-making tool for rapid diagnosis . However, because of its complexity, the agglutination test can be used only in pathology laboratories.

Lett Appl Microbiol, 2004, 39(4), 341 - 6
Characterization of Streptococcus bovis from the rumen of the dromedary camel and Rusa deer; Ghali MB et al.; AIMS: Isolation and characterization of Streptococcus bovis from the dromedary camel and Rusa deer . METHODS AND RESULTS: Bacteria were isolated from the rumen contents of four camels and two deer fed lucerne hay by culturing on the semi-selective medium MRS agar . Based on Gram morphology and RFLP analysis seven isolates, MPR1, MPR2, MPR3, MPR4, MPR5, RD09 and RD11 were selected and putatively identified as Streptococcus . The identity of these isolates was later confirmed by comparative DNA sequence analysis of the 16S rRNA gene with the homologous sequence from S . bovis strains, JB1, C14b1, NCFB2476, SbR1, SbR7 and Sb5, from cattle and sheep, and the Streptococcus equinus strain NCD01037T . The percentage similarity amongst all strains was >99%, confirming the identification of the camel isolates as S . bovis . The strains were further characterized by their ability to utilize a range of carbohydrates, the production of volatile fatty acids (VFA) and lactate and the determination of the doubling time in basal medium 10 supplemented with glucose . All the isolates produced l-lactate as a major fermentation end product, while four of five camel isolates produced VFA . The range of carbohydrates utilized by all the strains tested, including those from cattle and sheep were identical, except that all camel isolates and the deer isolate RD11 were additionally able to utilize arabinose . CONCLUSIONS: Streptococcus bovis was successfully isolated from the rumen of camels and deer, and shown by molecular and biochemical characterization to be almost identical to S . bovis isolates from cattle and sheep . SIGNIFICANCE AND IMPACT OF THE STUDY: Streptococcus bovis is considered a key lactic acid producing bacterium from the gastrointestinal tract of ruminants, and has been implicated as a causative agent of lactic acidosis . This study is the first report of the isolation and characterization of S . bovis from the dromedary camel and Rusa deer, and suggests a major contributive role of this bacterium to fermentative acidosis.

Clin Microbiol Infect, 2004 Sep, 10(9), 851 - 4
Increase of resistance to macrolides in invasive Streptococcus pneumoniae in Spain (2000-2001); Oteo J et al.; This study examined the antimicrobial resistance of 1,278 invasive Streptococcus pneumoniae isolates from 41 Spanish laboratories participating in the European Antimicrobial Resistance Surveillance System (EARSS) during 2000 and 2001 . Twenty-nine laboratories participated during both years and provided 950 of the isolates . Each laboratory used its own susceptibility testing methods . External quality assessment was performed annually by each participating laboratory . Significant increases in penicillin and erythromycin resistance were observed between 2000 and 2001 . This increase was particularly noticeable in isolates from the laboratories participating during both years and in isolates from children and elderly patients.

Clin Microbiol Infect, 2004 Sep, 10(9), 797 - 803
A cross-sectional survey of the prevalence of Streptococcus pneumoniae nasopharyngeal carriage in Belgian infants attending day care centres; Malfroot A et al.; Nasopharyngeal carriage is a major factor in the transmission of pneumococcal disease . The aim of this study was to determine the prevalence of asymptomatic nasopharyngeal carriage of Streptococcus pneumoniae and the distribution of serogroups and serotypes in children aged 3-36 months attending day care centres in Belgium . A single nasopharyngeal swab was cultured from 467 children attending 30 different day care centres between December 2000 and March 2001 . S . pneumoniae isolates were serotyped and their antibiotic susceptibilities assessed by disk diffusion . The overall nasopharyngeal carriage rate for S . pneumoniae was 21% in the 467 children . None of the commonly accepted risk factors studied was associated significantly with carriage . Capsular serotypes isolated were 19F (27.3%), 6B (20.2%), 23F (19.2%), 19A (10.1%), 6A (7.1%), 14 (5.1%) and others (11.0%) . Theoretical coverage by the seven-valent (serotypes 4, 6B, 9V, 14, 18C, 19F and 23F) pneumococcal conjugate vaccine was 73.7% . Fourteen (14.1%) of 99 strains were non-susceptible to penicillin, 48 (48.5%) to tetracycline and 61 (61.6%) to erythromycin . Theoretical coverage by the seven-valent pneumococcal conjugate vaccine was 93% for the penicillin-resistant serotypes, 69% for the tetracycline-resistant serotypes and 75% for the erythromycin-resistant serotypes . Use of the seven-valent pneumococcal conjugate vaccine could potentially reduce nasopharyngeal carriage of the antibiotic-resistant strains.

Clin Microbiol Infect, 2004 Sep, 10(9), 791 - 6
Serotypes and clinical manifestations of invasive group B streptococcal infections in western Sweden 1998-2001; Persson E et al.; This study monitored the serotypes of Streptococcus agalactiae (group B streptococcus; GBS) isolated from invasive infections in western Sweden and investigated possible relationships between serotype, age and clinical manifestations . Invasive GBS isolates were collected prospectively during 1998-2001 at six laboratories, covering two counties with a population of 1.8 million, and were serotyped by coagglutination . Clinical data were obtained from hospital notes . In total, 161 invasive strains (50 from neonates and infants aged < 3 months, and 111 from adults) were serotyped . The commonest serotypes from neonates and infants were serotypes III (60%), V (22%) and Ia (10%), and from adults were serotypes V (42%) and III (25%) . Serotype V had doubled in frequency among both children and adults compared to a previous study from the same area in 1988-1997 . Most (80%) of the adults had an underlying medical condition . No relationship was found between serotype and clinical manifestations . However, the study demonstrated the importance of active surveillance of GBS serotypes and the difficulties of formulating a multivalent polysaccharide conjugate vaccine against GBS.

Folia Med (Plovdiv), 2001, 43(1-2), 38 - 41
Comparative in vitro study of pulp capping materials; Tsanova ST et al.; AIM: In a comparative in vitro study we examined the bactericidal effect, adhesion and shrinkage of 5% potassium nitrate in Carboxy-Adhaesor, 5% potassium chloride in Carboxy-Adhaesor, Carboxy-Adhaesor, Adhaesor and Dycal . MATERIAL AND METHODS: The bactericidal effect of the investigated pulp capping materials on the isolated microorganisms Staphylococcus aureus, Staph . epidermidis, Streptococcus viridans alpha-haemolyticus, Streptococcus pneumoniae and Streptococcus beta-haemolyticus was assessed by the diffusion method around each disk in mm . The adhesion and shrinkage were assessed after hardening of the material . RESULTS: The results obtained showed higher bactericidal activity of polycarboxylate cements in comparison to Adhaesor and Dycal . The largest zone of inhibition was found around the disks with polyacrilic acid, followed by 5% KNO3 in polyacrilic acid, 5% KCl in polyacrilic acid; significantly smaller is the zone around Dycal . The difference was statistically significant (p<0.01) . The adhesion and shrinkage of polycarboxylate cements were estimated as very good, better than those of Adhaesor and Dycal . CONCLUSION: The bactericidal effect of 5% KNO3 in polycarboxylate cement is very good for the microorganisms isolated from deep caries . The adhesion to hard tissues is very good, which suggests good marginal adaptation to the cavity.

Surg Infect (Larchmt), 2004 Summer, 5(2), 200 - 4
Intramedullary abscess from group F Streptococcus; Vora YA et al.; BACKGROUND: Intramedullary abscesses are rare and may be misdiagnosed . We report the case of a 54-year-old man with carcinoma of the gastroesophageal junction who presented after thoracotomy with hemiparesis and a ring-enhancing intramedullary lesion at C2-3 on magnetic resonance imaging . METHODS: Individual case report and literature review . RESULTS: Although the lesion was initially mistaken for metastasis, at surgery an intramedullary abscess was discovered, from which group F Streptococcus was isolated . Conclusions : Although other streptococcal species have been found in abscesses of the spinal cord, this particular strain has not been identified previously as a cause of such abscesses . Prompt surgical evacuation is recommended, and should be followed by appropriately tailored antibiotic therapy.

West Indian Med J, 2004 Jun, 53(3), 164 - 9
Survival and surface adherence ability of bacterial pathogens in oral liquid pharmaceuticals and their containers; Egwari LO et al.; The survival and surface adherence ability of Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa in nutrient broth and in five oral liquid pharmaceuticals (nivaquine syrup, cough mixture, paracetamol elixir, cotrimoxazole and vitamin C) were investigated The bacteria grew more in nutrient broth than in the pharmaceuticals (p < 0 . 001) and the recovery of stressed cells was enhanced when 3% Tween 80 was used as the recovery medium as against the use of normal saline (p < 0.01) . The Gram-negative bacteria were more adapted to the pharmaceuticals than their Gram-positive counterparts . Klebsiella pneumoniae and Ps . aeruginosa were recovered in large numbers from nivaquine and cotrimoxazole suspensions that did not support the growth of the other bacteria . The effect of bacterial growth on the physico-chemical properties of the pharmaceuticals was also evaluated The properties were not altered significantly except for pH shifts of 0.3 to 1.1 caused by E . coli and S . aureus in paracetamol and vitamin C . Adherence capability was found to correlate with the survival ability of the bacteria . Populations on coupons were significantly higher when nutrient broth was used as the suspending medium compared with any of the pharmaceuticals (p < 0.01) . Rubber and plastic coupons were significantly more accessible to the bacteria than glass coupon as revealed by the high population of bacteria recovered from their surfaces.

Can J Vet Res, 2004 Jul, 68(3), 236 - 40
Evaluation of a ceftiofur-washed whole cell Streptococcus suis bacterin in pigs; Pallares FJ et al.; The efficacy of currently available washed whole cell Streptococcus suis bacterins is generally poor . We developed and tested the efficacy of a novel ceftiofur-washed whole cell bacterin . Sixty-six, 2-week-old specific pathogen free (SPF) pigs were randomly divided into 5 groups . Three groups were vaccinated 28 and 14 d prior to challenge . The 3 ceftiofur-washed whole cell bacterins each contained 1 of 3 different adjuvants (Montanide ISA 25, Montanide ISA 50, and Saponin) . Pigs exhibiting severe central nervous system disease or severe joint swelling and lameness were euthanized immediately and necropsied . All remaining pigs were necropsied at 14 d post inoculation . The ceftiofur-washed whole cell S . suis bacterin with Montanide ISA 50 adjuvant significantly (P < 0.05) reduced bacteremia, meningitis, pneumonia, and mortality associated with S . suis challenge . Further work on this novel approach to bacterin production is warranted.

Proteomics, 2004 Sep, 4(9), 2624 - 8
Use of surface-enhanced laser desorption/ionization -time of flight to explore bacterial proteomes; Barzaghi D et al.; Surface-enhanced laser desorption/ionization (SELDI)-time of flight is a recent technology that allows proteomic analysis with limited material requirements . This characteristic makes it a valuable technique for microbiologists handling problematic samples, such as low cell number cultures . We compared three simple procedures for protein extraction from bacteria for compatibility with the ProteinChip Array; we also determined the amount of protein required for each analysis . The protocol for the SELDI analysis was evaluated by generating protein expression profiles of a Streptococcus pneumoniae strain grown in different conditions and those of different strains of the same species . The protocol also was successfully applied to a wide range of Gram positive and negative bacteria . The results of this study suggest the appropriateness of this technology for microorganism protein profiling as complementary or alternative to two-dimensional gel electrophoresis.

Fitoterapia, 2004 Sep, 75(6), 596 - 8
Anticariogenic activity of some tropical medicinal plants against Streptococcus mutans; Hwang JK et al.; The methanol extracts of five tropical plants, Baeckea frutescens, Glycyrrhiza glabra, Kaempferia pandurata, Physalis angulata and Quercus infectoria, exhibited potent antibacterial activity against the cariogenic bacterium Streptococcus mutans . In particular, G . glabra, K . pandurata and P . angulata conferred fast killing bactericidal effect against S . mutans in 2 min at 50 microg/ml of extract concentration.

Microb Pathog, 2004 Sep, 37(3), 125 - 9
Role of bovine herpesvirus 4 in bacterial bovine mastitis; Kalman D et al.; In order to study the role played by bovine herpesvirus 4 (BoHV-4) in bovine mastitis, PCR experiments were performed on a Hungarian dairy herd of 2000 cows . Milk cells were tested with a nested PCR adjusted to detect the virus in the milk . Thirty to forty-one percentage of the udders of 101 cows with bacterial mastitis (Escherichia coli, Streptococcus uberis or Staphylococcus aureus) gave positive results, whereas less than 6% of the milk samples were positive for BoHV-4 from 118 animals with healthy udders . The mastitis status of these 118 healthy cows was followed throughout the milking period; 4.2% had clinical, and 25.42% had subclinical mastitis . By the end of the milking period, more than 90% of the cows shed the virus in their milk, regardless of the bacterial status of the udder . No correlation was found between the virus shed, the somatic cell count, and the bacterial status of the udder . Viral DNA was detected in the wall of the milk duct . These results demonstrate that BoHV-4 neither causes mastitis directly nor plays a role in the initiation of the process, but later, when bacterial infection of the udder occurs, the reactivated virus replicates in the immune cells of the udder and/or in the epithelial cells of the milk ducts and may be responsible for more severe, prolonged mastitis . As mastitis is a crucial problem of milk production, this virus may be considered a possible predisposing factor and also an agent of secondary udder infections in prolonged mastitis cases.

Arch Pediatr, 2004 Sep, 11(9), 1145 - 51
{Evaluation of varicella complications through a retrospective hospital survey in a paediatric center over 16 years in France}; Mallet E et al.; OBJECTIVE: Evaluation of the varicella severity through a prevalence study of hospital admissions justified by a complication directly related to the onset of an acute episode of varicella . METHODS: Retrospective study in one paediatric center in France with a follow-up of a paediatric cohort from April 1987 to December 2002 . This general paediatric hospital recruits children from a 400,000 inhabitants area . Inclusion criterion: diagnosis main or associated of varicella . Exclusion criteria: congenital or acquired immunodepression, including long-term oral high dosage steroid therapy . RESULTS: Three hundred and forty-three (343) complications of varicella were reported in 309 children hospitalised for a symptom in relationship with varicella . Most of children (75%) were <2 years of age . The annual number of hospitalisations varied with a maximum of 44 . An increase of the number of hospitalisations was reported since 1997 but particularly since 2000 . Main complications were gastro-intestinal (75), neurological (68), bronchopulmonary (52), and skin and soft tissue infections (52) . Superinfections of soft tissues such as Streptococcus pyogenes cellulitis and life-threatening complications, which occurred in children treated by a short-course of corticosteroids for an acute episode such as an asthma crisis, were mostly noticed since 1995 . Two deaths occurred . CONCLUSION: These data collected over 16 years as part of a retrospective survey of a paediatric cohort show that varicella, often considered as a mild disease, can be responsible for severe complications in young immunocompetent children . The digestive complications (30%) are the main complication in our study with existence of gingivitis-stomatitis but also lower digestive manifestations (erosive gastritis aspect through endoscopy) . These data have all the more to be taken into account because a vaccine, developed for healthy children, is now available in France . A national survey of hospitalised varicella has been set up since March 2003.

Arch Pediatr, 2004 Sep, 11(9), 1046 - 53
{Hepatic abscesses in childhood: retrospective study about 33 cases observed in New-Caledonia between 1985 and 2003}; Guittet V et al.; Hepatic abscesses in childhood are rarely observed in Europe . The aim of this word was to study how to diagnose and how to treat an hepatic abscess . METHODS: Between 1985 and 2003, we recensed retrospectively 33 cases of hepatic abscesses hospitalised in the paediatric unit of Noumea . RESULTS: Children were mainly melanesians (79%), 7 years old on average, having abdominal pains, a clinical and biological infectious syndrome, and abscesses images on ultrasonography or computed tomography . The identified micro-organisms included Entamoeba histolytica in 30% (10 cases); Staphylococcus aureus in 15% (five cases), Staphylococcus coagulase negative in 6% (two cases), Streptococcus D in 3% (one case); Bartonella henselae in 9% (three cases); ascaris in 6% (two cases); Mycobacterium tuberculosis in 6% (two cases) . In eight cases no bacteria was identified (24%) but the good evolution after antibiotics and the negative amoebic serology looked like pyogenic abscesses . Two abscesses were aspirated, two were drained, one child had a surgical intervention . There was no death . Following a mean duration of 1 month for antibiotics treatment, outcome was always favourable . CONCLUSION: Diagnosis of hepatic abscess can be difficult . Ultrasonography shows the abscess but not the causal agent . The amoebic serology is sensible, consequently, its negativity leads to evoke a pyogenic agent . Early antibiotic treatment against pyogenic, anaerobic bacteria, and Entamoeba histolytica is required . Hepatic abscesses in ascaridiosis, tuberculosis and cat-scratch disease are less frequently encountered . If diagnosis remains doubtful or clinical evolution worsens, or if abscess volume increases, a percutaneous aspiration or drainage is needed.

Shanghai Kou Qiang Yi Xue, 2004 Aug, 13(4), 256 - 8
{The inhibitive effect of IgY toothpaste against oral Streptococcus mutans}; Chi ZB et al.; PURPOSE: To study the effect of the toothpaste containing IgY against oral Streptococcus mutans . METHODS: 140 subjects were divided into 2 groups randomly (test group and control group) . Before the beginning of the test, every subject underwent a elution period in order to lessen the other interference factors, then used different toothpastes were used respectively and the test began . Streptococcus mutans values were determined with Dentocult SM Strip just before test, at 1, 3, 7, 30 days after toothpaste used and 14 days after stopping toothpaste used . RESULTS: (1) In test group,Streptococcus mutans values decreased at 1 day after toothpaste used . In control group Streptococcus mutans values decreased at 3 days after toothpaste used . (2) Streptococcus mutans values decreased gradually in each groups after toothpaste used . (3) In test group, 2 weeks after stopping toothpaste used, Streptococcus mutans values were still suppressed . CONCLUSION: The application of the toothpaste containing IgY may reduce oral Streptococcus mutans levels significantly.

J Mater Sci Mater Med, 1998, 9(2), 117 - 20
Adherent bacteria cells in five dental materials: sonication effect; Yoshida Y et al.; Adherent bacterial cells on the surfaces of two dental porcelain ceramics, three composite resins and human enamel were examined using four types of bacteria strains . Their adherent cells were counted on saliva-coated and uncoated material surfaces after sonication, and contact angle and zeta potential were measured for each adherent cell tested . A correlation between contact angle and bacterial cells on an uncoated surface was found to be higher in two Streptococcus sanguis cells than in S . mutans Ingbritt and S . sobrinus OMZ 176, whereas there appeared to be a higher correlation between S . mutans Ingbritt or S . sobrinus OMZ 176 and zeta potential on the uncoated surface . On the saliva-coated surface, a significantly high correlation was found between the adherent cells, with the exception of S . sanguis ATCC 10 557, and the zeta potential . Contact angle and zeta potential values were small when the surfaces of the materials were coated with saliva, as compared with those on the uncoated surface . The sonication condition (120 s) of adherent cells on the surface of the material significantly depended on the types of bacteria cells, showing that S . mutans Ingbritt (>50-60%) had a greater removal percentage than the others (<50%) .

J Mater Sci Mater Med, 2000 Oct, 11(10), 637 - 42
Effect of hydrophobicity on in vitro streptococcal adhesion to dental alloys; Grivet M et al.; Non-specific interactions such as electrostatic interactions, and surface free energy are of importance in bacterial adhesion to dental surfaces as they determine whether or not bacteria are attracted to the surface . The relationship between adherence of Streptococcus mitis, S . mutans, S . oralis and S . sanguinis on precious and non-precious dental alloys, and the bacterial and alloy surface hydrophobicities (a measure of the surface free energy) was studied . The number of adhering bacteria was determined by fluorescence microscopy counts . The hydrophobicity of the bacteria and alloy surfaces were evaluated by adhesion to hexadecane and water contact angles, respectively . Our results showed that (i) the surfaces of the tested alloys were hydrophobic, (ii) S . sanguinis, S . mutans and S . oralis were hydrophobic, and (iii) S . mitis was hydrophilic . S . oralis, the more hydrophobic strain, demonstrated the highest adherence on the tested materials, whereas S . mitis adhered least on the hydrophobic surfaces . For the tested alloys, bacterial adherence was highest for the high gold content alloy, and lowest for the non-precious alloy . Our results showed that for the tested bacterial strains, there was a significant correlation between bacterial adhesion and substratum hydrophobicity: hydrophobic metal surfaces favor adhesion of hydrophobic bacteria .

Chemotherapy, 2004 Oct, 50(4), 184 - 9 Epub 2004 Sep 03.
Antimicrobial resistance of Streptococcus pneumoniae isolates of outpatients in Germany, 1999-2000; Reinert RR et al.; BACKGROUND: The aim of the study was to determine the prevalence of antimicrobial resistance among clinical isolates of Streptococcus pneumoniae during the winter of 1999-2000 in Germany . METHODS: Pneumococcal isolates were prospectively collected by 14 different clinical microbiology laboratories . Minimal inhibitory concentrations of penicillin G, erythromycin A, clarithromycin, roxithromycin, azithromycin, clindamycin, levofloxacin and telithromycin were determined by the broth microdilution method . RESULTS: Among 328 strains 4.6% were nonsusceptible to penicillin G (intermediate and resistant strains) and 9.5% were resistant to erythromycin A . Analysis of erythromycin-resistant strains for the underlying resistance determinants revealed that 12 (38.7%) belonged to the erm(B) and 19 (61.3%) to the mef(E) type of resistance . Among the macrolide-resistant strains, serotypes 19F (n = 9) and 14 (n = 8) were the predominant types . CONCLUSIONS: Macrolide resistance in Germany is of growing concern and mainly due to the high prevalence of pneumococci expressing the mef(E) type of resistance . Copyright (c) 2004 S . Karger AG, Basel.

J Am Anim Hosp Assoc, 2004 Sep-Oct, 40(5), 418 - 22
Group g streptococcal toxic shock-like syndrome in three cats; Taillefer M et al.; Three 8-week-old kittens were presented with a history of acute, generalized weakness and severe fever . One cat was dead upon presentation, and necropsy findings were supportive of a group G Streptococcus spp . septicemia . During their clinical courses, two of the three kittens developed a progressive, marked swelling of one or more limbs . One moribund and severely hypothermic cat was euthanized a few hours after presentation, and necropsy was also supportive of a group G Streptococcus spp . septicemia . One kitten recovered . Group G streptococcal toxic shock-like syndrome was suspected because of the fulminant progression of the septicemia.

Dermatol Online J . 2004 Jul 15;10(1):7.
Streptococcal toxic shock syndrome and sepsis manifesting in a patient with chronic rheumatoid arthritis; Chikkamuniyappa S; Streptococcal-toxic-shock syndrome is caused by virulent strains of exotoxin-producing streptococcus, almost always group-A organisms such as Streptococcus pyogenes . It has often been described in the setting of surgical wounds, burns, childbirth, diabetics, elderly, neonates, and immunocompromised hosts, where the portal of entry is the skin . Our patient was on steroids and nonsteroidal anti-inflammatory drugs for chronic rheumatoid arthritis and developed this deadly infection after a fall.

An Med Interna, 2004 Jul, 21(7), 337 - 9
{Psoas muscle abscess by Streptococcus agalactiae as a of presentation of fever of unknown origin}; Khosravi Shahi P et al.; We present the case of a patient with precedents of endometrial carcinoma treated by surgery and radiotherapy, which presented a psoas abscess by Streptococcus agalactiae as cause of fever of unknown origin, which answered favorably to the antibiotherapy and surgical drainage.

Zh Mikrobiol Epidemiol Immunobiol, 2004 May-Jun, (3), 69 - 73
{Immunoserodiagnosis of acute Streptococcus pneumoniae and Chlamydia pneumoniae infections in the period of epidemic rise of non-hospital pneumonia in children in St . Petersburg, 1998-2001}; Vishniakova LA et al.; The dynamics of the antibody formation to S . pneumoniae and C . pneumoniae in children during the epidemic outbreak of non-hospital pneumonia in St . Petersburg in 1998-2001 was studied . For the first time the inhibiting influence of acute C . pneumoniae infection on the synthesis of antibodies to S . pneumoniae in acute mixed infection was established . The prolonged (up to days 29-39 of the disease) circulation of IgM and IgG antibodies in acute chlamydial infection, as well as the prevalence of the primary infectious process, were detected.

J Infect Dis, 2004 Oct 1, 190(7), 1212 - 20 Epub 2004 Aug 18.
Differences in survival, brain damage, and cerebrospinal fluid cytokine kinetics due to meningitis caused by 3 different Streptococcus pneumoniae serotypes: evaluation in humans and in 2 experimental models; Ostergaard C et al.; BACKGROUND: Experimental meningitis with Streptococcus pneumoniae serotypes 1, 3, and 9 has resulted in pronounced differences in disease severity, but clinical meningitis studies addressing serotype-related differences in case-fatality rates are lacking . METHODS: Study subjects were Danish patients with pneumococcal meningitis due to serotype 1 (n=38), 3 (n=69), or 9V (n=59) during 1990-2002 for whom clinical information was available . The 3 serotypes were tested for brain damage and cerebrospinal fluid (CSF) inflammatory kinetics in 2 experimental models of meningitis . RESULTS: Patients with serotype 1 had a significantly lower case-fatality rate (3%), compared with patients with serotypes 3 (23%) and 9V (32%) (P=.0047, log-rank test) . Age and serotype were independent prognostic factors for fatal outcome . In experimental meningitis, the median number of areas per brain slide with brain damage was significantly lower in rats infected with serotype 1 than in rats infected with serotypes 3 and 9V . Three distinct patterns of brain damage were observed: serotype 1, cortical hemorrhage; serotype 3, cortical necrosis and abscess formation; and serotype 9V, subcortical (callosal) abscess formation . Serotype 1 caused the poorest bacterial growth and lowest CSF levels of white blood cells, tumor necrosis factor- alpha, and interleukin-8 (P<.05) . CONCLUSION: Case-fatality rates of patients with pneumococcal meningitis, the degree and pattern of brain damage, and CSF cytochemical alterations in experimental pneumococcal meningitis differ according to serotype.

J Infect Dis, 2004 Oct 1, 190(7), 1203 - 11 Epub 2004 Aug 25.
Temporal and geographic stability of the serogroup-specific invasive disease potential of Streptococcus pneumoniae in children; Brueggemann AB et al.; A meta-analysis study design was used to analyze 7 data sets of invasive and carriage pneumococcal isolates recovered from children, to determine whether invasive disease potential differs for each serotype and, if so, whether it has changed over time or differs geographically . Serotype- and serogroup-specific odds ratios (ORs) were calculated for each study and as a pooled estimate, with use of serotype 14 as the reference group . ORs varied widely: the serotypes with the highest ORs (1, 5, and 7) were 60-fold more invasive than those with the lowest ORs (3, 6A, and 15) . There was a significant inverse correlation between invasive disease and carriage prevalence for the serotypes that we considered, which implies that the most invasive serotypes and serogroups were the least commonly carried and that the most frequently carried were the least likely to cause invasive disease . There was no evidence of any temporal change or major geographical differences in serotype- or serogroup-specific invasive disease potential.

Indian J Med Sci, 2004 Aug, 58(8), 327 - 33
Characteristics of acute bacterial meningitis in Southeast Turkey; Celal A et al.; BACKGROUND: Acute bacterial meningitis (ABM) remains a significant worldwide cause of death in adults . Even in the antibiotic era, the mortality rate in ABM remains significant and has been reported in the range of 8-40% . AIM: The aim of this study was to assess the characteristics of epidemiology, clinical manifestations, treatment modalities and outcome of patients with ABM in Southeast Turkey . SETTINGS AND DESIGN: This retrospective study included all cases of community-acquired ABM diagnosed and treated in Dicle University Hospital between June 1996 and December 2002 . METHODS AND PATIENTS: The study group consisted of 186 adult patients (110 male, 76 female) with ABM, those patients who are older than 14 years, followed up at Dicle University Hospital from June 1996 to December 2002 . Patients' charts were retrospectively reviewed, clinical characteristics were recorded and final data were analyzed . STATISTICAL ANALYSIS: In statistical analyses, the Chi-square test was used for binary variables and Student's t-test for continuous variables . RESULTS: The patients' mean age was 30.2 +/- 15.3 years (range 14 to 90 years) . On admission, typical symptoms of meningitis were found in most of the patients: headache in 92.5%, fever in 88.2%, and nuchal rigidity in 80.1% . The main predisposing factor for ABM was otitis media (40 patients, 21.5%) and closed head trauma (12 patients, 6.5%) . Streptococcus pneumonia was the most common identified pathogen . Twenty-nine patients (15.6%) died during hospitalization period . In multivariate analyses, the significant mortality factor was found as initial level of consciousness, low cerebrospinal fluid/blood glucose ratio, high erythrocyte sedimentation rate and initial treatment by penicillin G . CONCLUSIONS: Although still remains as a serious infection, early diagnosis and effective treatment may reduce fatal outcome and improve the course of the disease in patients with ABM . Ceftriaxone should be considered as the drug of choice for initial empirical therapy, while waiting culture results and vancomycin must be withheld for patients having increased risk of penicillin resistant pneumococci strains.

Appl Environ Microbiol, 2004 Sep, 70(9), 5244 - 51
Molecular characterization of CcpA and involvement of this protein in transcriptional regulation of lactate dehydrogenase and pyruvate formate-lyase in the ruminal bacterium Streptococcus bovis; Asanuma N et al.; A ccpA gene that encodes global catabolite control protein A (CcpA) in Streptococcus bovis was identified and characterized, and the involvement of CcpA in transcriptional control of a gene (ldh) encoding lactate dehydrogenase (LDH) and a gene (pfl) encoding pyruvate formate-lyase (PFL) was examined . The ccpA gene was shown to be transcribed as a monocistronic operon . A catabolite-responsive element (cre) was found in the promoter region of ccpA, suggesting that ccpA transcription in S . bovis is autogenously regulated . CcpA required HPr that was phosphorylated at the serine residue at position 46 (HPr-{Ser-P}) for binding to the cre site, but glucose 6-phosphate, fructose 1,6-bisphosphate, and NADP had no effect on binding . Diauxic growth was observed when S . bovis was grown in a medium containing glucose and lactose, but it disappeared when ccpA was disrupted, which indicates that CcpA is involved in catabolite repression in S . bovis . The level of ccpA mRNA was higher when cells were grown on glucose than when they were grown on lactose, which was in line with the level of ldh mRNA . When cells were grown on glucose, the ldh mRNA level was lower but the pfl mRNA level was higher in a ccpA-disrupted mutant than in the parent strain, which suggests that ldh transcription is enhanced and pfl transcription is suppressed by CcpA . The ccpA-disrupted mutant produced less lactate and more formate than the parent, probably because the mutant had reduced LDH activity and elevated PFL activity . In the upper region of both ldh and pfl, a cre-like sequence was found, suggesting that the complex consisting of CcpA and HPr-{Ser-P} binds to the possible cre sites . Thus, CcpA appears to be involved in the global regulation of sugar utilization in S . bovis.

Biochem Pharmacol, 2004 Oct 1, 68(7), 1401 - 10
Inhibition of hyaluronan export from human fibroblasts by inhibitors of multidrug resistance transporters; Prehm P et al.; In a previous report we described the export of hyaluronan from Streptococcus pyogenes by an ABC transporter . Extending these findings a sequence homology search against human proteins revealed a strong homology to the multidrug resistance transporter ABC-B (MDR-1) and ABC-C (MRP 5) . Using several inhibitors directed against these and other transporters, a decreased hyaluronan production in cell culture as well as in hyaluronan synthase activity in purified membrane fractions was observed . The inhibitory capacity (IC(50) concentrations) was compared the with reported IC(50)- or the K(i)-concentrations for individual transporters . These analyses revealed that hyaluronan is synthesized within the cytoplasm of mammalian cells and actively secreted into the pericellular space by energy dependent transport proteins . While inhibition of several transport proteins resulted in a decrease of hyaluronan export, inhibition of the MRP5 transporter was the most effective one to decrease hyaluronan in the cell culture supernatant indicating that hyaluronan export is one physiological role of this transport protein.

J Immunol Methods, 2004 Aug, 291(1-2), 109 - 22
High efficiency creation of human monoclonal antibody-producing hybridomas; Dessain SK et al.; The native human antibody repertoire holds unexplored potential for the development of novel monoclonal antibody therapeutics . Current techniques that fuse immortal cells and primary B-lymphocytes are sub-optimal for the routine production of hybridomas that secrete human monoclonal antibodies . We have found that a murine cell line that ectopically expresses murine interleukin-6 (mIL-6) and human telomerase (hTERT) efficiently forms stable human antibody-secreting heterohybridomas through cell fusion with primary human B-lymphocytes . The hybrid cells maintain secretion of human antibodies derived from the primary B-lymphocytes through multiple rounds of cloning . Using splenic B-lymphocytes from a patient immunized with a Streptococcus pneumoniae capsular polysaccharide vaccine, we have succeeded in creating hybridomas that secrete human monoclonal antibodies specific for S . pneumoniae antigens . Using peripheral blood lymphocytes, we have similarly cloned a human antibody that binds a viral antigen . These experiments establish that SP2/0-derived cell lines ectopically expressing mIL-6 and hTERT will enable the rapid cloning of native human monoclonal antibodies.

J Bacteriol, 2004 Sep, 186(18), 5997 - 6002
Regulation of the intracellular free iron pool by Dpr provides oxygen tolerance to Streptococcus mutans; Yamamoto Y et al.; Dpr is an iron-binding protein required for oxygen tolerance in Streptococcus mutans . We previously proposed that Dpr could confer oxygen tolerance to the bacterium by sequestering intracellular free iron ions that catalyze generation of highly toxic radicals (Y . Yamamoto, M . Higuchi, L . B . Poole, and Y . Kamio, J . Bacteriol . 182:3740-3747, 2000; Y . Yamamoto, L . B . Poole, R . R . Hantgan, and Y . Kamio, J . Bacteriol . 184:2931-2939, 2002) . Here, we examined the intracellular free iron status of wild-type (WT) and dpr mutant strains of S . mutans, before and after exposure to air, by using electron spin resonance spectrometry . Under anaerobic conditions, free iron ion concentrations of WT and dpr strains were 225.9 +/- 2.6 and 333.0 +/- 61.3 microM, respectively . Exposure of WT cells to air for 1 h induced Dpr expression and reduced intracellular free iron ion concentrations to 22.5 +/- 5.3 microM; under these conditions, dpr mutant cells maintained intracellular iron concentration at 230.3 +/- 28.8 microM . A decrease in cell viability and genomic DNA degradation was observed in the dpr mutant exposed to air . These data indicate that regulation of the intracellular free iron pool by Dpr is required for oxygen tolerance in S . mutans.

Mol Microbiol, 2004 Sep, 53(6), 1583 - 99
Subcellular sites for bacterial protein export; Campo N et al.; Most bacterial proteins destined to leave the cytoplasm are exported to extracellular compartments or imported into the cytoplasmic membrane via the highly conserved SecA-YEG pathway . In the present studies, the subcellular distributions of core components of this pathway, SecA and SecY, and of the secretory protein pre-AmyQ, were analysed using green fluorescent protein fusions, immunostaining and/or immunogold labelling techniques . It is shown that SecA, SecY and (pre-)AmyQ are located at specific sites near and/or in the cytoplasmic membrane of Bacillus subtilis . The localization patterns of these proteins suggest that the Sec machinery is organized in spiral-like structures along the cell, with most of the translocases organized in specific clusters along these structures . However, this localization appears to be independent of the helicoidal structures formed by the actin-like cytoskeletal proteins, MreB or Mbl . Interestingly, the specific localization of SecA is dynamic, and depends on active translation . Moreover, reducing the phosphatidylglycerol phospholipids content in the bacterial membrane results in delocalization of SecA, suggesting the involvement of membrane phospholipids in the localization process . These data show for the first time that, in contrast to the recently reported uni-ExPortal site in the coccoid Streptococcus pyogenes, multiple sites dedicated to protein export are present in the cytoplasmic membrane of rod-shaped B . subtilis.

Oftalmologia, 2004, 48(2), 102 - 10
{Experimental animal studies in uveitis}; Dogan D et al.; The aim of this study is to observe that if inject the Streptococcus beta-hemolytic group A in anterior chamber at rabbit bring about an acute uveitis.

J Leukoc Biol, 2004 Dec, 76(6), 1142 - 50 Epub 2004 Dec.
Membrane retrieval in neutrophils during phagocytosis: inhibition by M protein-expressing S . pyogenes bacteria; Bauer S et al.; During phagocytosis and phagosome maturation, complex membrane traffic events must be coordinated . We have observed, using fluorescent fluid-phase and membrane markers, that in the human neutrophil, internalization of nonopsonized, Gram-positive bacteria, but not of latex beads, is accompanied by a rapid and localized formation of pinosomal structures . This pinocytic response is calcium-dependent but insensitive to actin cytoskeleton disruption and wortmannin treatment . Contrary to what we observe, endosomal structures usually are considered to participate in phagosome formation by providing necessary membrane to forming phagosomes . Instead, our results show a coupling between neutrophil secretory and membrane-retrieval processes during phagosome maturation, and we suggest that the observed, localized pinocytic response is linked to the secretion of azurophilic granules toward nascent phagosomes . Accordingly, M and M-like protein-expressing Streptococcus pyogenes bacteria, which are able to survive inside neutrophil phagosomes, inhibit both the secretion of azurophilic granules to phagosomes and pinosome formation.

Cell Microbiol, 2004 Oct, 6(10), 939 - 52
Transcriptome analysis and gene expression profiles of early apoptosis-related genes in Streptococcus pyogenes-infected epithelial cells; Nakagawa I et al.; Epithelial cells are the initial sites of host invasion by group A Streptococcus pyogenes (GAS), and GAS infection of epithelial cells has been suggested to induce apoptosis . We previously reported that the induction of apoptosis is strongly associated with the protein F1-mediated invasion . We present here the gene expression profiles of the human epithelial HEp-2 cells during GAS-induced apoptosis, using serial gene analysis of expression (SAGE) analysis and macroarray analysis of apoptosis-related genes . Serial gene analysis of expression revealed the downregulation of voltage-dependent anion channels 1 and 2 genes and the upregulation of the cytochrome c oxidase and calcium binding protein genes (calpactin, calgizzarin and programmed cell death 6) . Macroarray analysis and quantitative RT-PCR analysis also revealed that the genes for IL-1beta, IL-12 p35, IL12 p40, and GM-CSF are also markedly induced by GAS invasion . Furthermore, caspase-1, -9, and -14 genes are significantly upregulated during GAS invasion . These observations indicated that apoptosis associated with GAS invasion is mainly induced by mitochondrial dysfunction and calcium regulation as well as by stress, and that these transcriptional controls may regulate the cellular response to GAS invasion.

Respir Med, 2004 Sep, 98(9), 865 - 71
Pneumolysin potentiates oxidative inactivation of alpha-1-proteinase inhibitor by activated human neutrophils; Cockeran R et al.; This study was designed to investigate the effects of the Streptococcus pneumoniae-derived, pro-inflammatory toxin, pneumolysin (8.37 and 41.75 ng/ml), on the oxidative inactivation of alpha-1-protease inhibitor (API) by chemoattractant-activated human neutrophils in vitro . The elastase inhibitory capacity (EIC) of API in supernatants from unstimulated neutrophils, neutrophils treated with pneumolysin only, or with the chemoattractant FMLP (1 microM) only, or the combination of the toxin with FMLP was measured by a colorimetric procedure based on the activity of added porcine elastase . The EIC of API was unaffected by exposure to pneumolysin only, unstimulated neutrophils, or neutrophils treated with pneumolysin only . However, exposure to FMLP-activated neutrophils resulted in a reduction of the EIC of API, which was significantly (P<0.05) augmented by pneumolysin (mean reductions of 16%, 43% and 83% for FMLP only and in combination with 8.37 and 41.75 ng/ml pneumolysin, respectively), and was attenuated by wortmannin (1 microM), an inhibitor of NADPH oxidase, the oxidant-scavenger methionine (100 microM), and depletion of Ca2+ from the cell-suspending medium . These pro-proteolytic interactions of pneumolysin with chemoattractant-activated neutrophils may contribute to the invasiveness of the pneumococcus.

Farmaco, 2004 Sep, 59(9), 691 - 6
Synthesis and antimicrobial activity of new 7beta-(benzo{a}dihydrocarbazolyloxyacetyl)-substituted cephalosporins; Rossello A et al.; Selected 7beta-(benzo{a}dihydrocarbazolyloxyacetyl)-substituted cephalosporins (1a-e) were synthesised and tested for their antimicrobial activity against Gram-positive and Gram-negative clinical pathogens . All compounds synthesised (1a-e) showed an in vitro antimicrobial activity similar to that of ceftriaxone and cefpirome against the Gram-positive bacteria, and superior to that of penicillin and cefaclor against pen-R Staphylococcus aureus species . Like all beta-lactam agents, compounds 1a-e were in an inactive Minimum Inhibitory Concentration (MIC > 32 microg/ml) against methicillin-resistant S . aureus species . Furthermore, as expected, no cross-resistance was observed against the erythromycin-resistant Staphylococcus pyogenes strain . Finally, it is worth underlining that compounds 1a and 1e showed a similar activity to that of ceftriaxone and superior to cefaclor against penicillin-resistant Streptococcus pneumoniae isolates, a key respiratory tract infection (RTI) causing pathogen difficult to treat with currently marketed antibiotics.

J Chemother, 2004 Jun, 16 Suppl 3, 1 - 19
The role of PK/PD parameters to avoid selection and increase of resistance: mutant prevention concentration; Blondeau JM et al.; The continuing escalation of antimicrobial resistant human pathogens and the limited number of new antimicrobial agents under development has dictated that our knowledge on the emergence of resistance and any potential strategies to slow the rate at which resistance occurs is of paramount importance . Investigations with fluoroquinolones resulted in the mutant prevention concentration (MPC) concept which represents a novel in vitro measurement of fluoroquinolone potency . In essence, the MPC defines the antimicrobial drug concentration threshold that would require an organism to simultaneously possess two resistance mutations for growth in the presence of the drug . An alternative definition is the drug concentration that prevents the growth of first-step resistant mutants or the minimal inhibitory concentration of the most resistant organism present in the heterogeneous bacterial population when tested against > or =10(9) organisms . From in vitro investigations, the new fluoroquinolones (gatifloxacin, gemifloxacin, moxifloxacin) were all found to have lower MPC values than did levofloxacin against clinical isolates of Streptococcus pneumoniae . Ciprofloxacin was found to have lower MPC values than levofloxacin against clinical isolates of Pseudomonas aeruginosa . When MPC data is applied to achievable and sustainable serum drug concentrations in the body, estimation of the time the serum drug concentration exceed both MIC and MPC values can be determined . This data along with kill data allows for an estimate of the amount of time drug concentration needs to exceed MIC/MPC values to not only result in significant kill but also to minimize resistance development . To date, MPC measurements have been determined in in vitro microbiological and pharmacological models and animal and human data are being investigated . The data summarized in this overview detail resistance issues for P . aeruginosa, S . pneumoniae and other pathogens . Also presented is a summary of the MPC concept and investigations completed to date . A brief summary of fluoroquinolone mechanisms of action and resistance is presented . Finally, some preliminary investigations with other classes of compounds are discussed . To date, very limited data is available to conclude if the MPC concept does or does not apply to other classes of antimicrobial agents.

Eur Respir J, 2004 Aug, 24(2), 263 - 6
Efficacious pleurodesis with OK-432 and doxorubicin against malignant pleural effusions; Kishi K et al.; Malignant pleural effusion develops frequently in patients with advanced lung cancer . Chemical pleurodesis is the most effective palliative treatment for these patients . The efficacy of pleurodesis using both OK-432, a preparation of Streptococcus pyogenes, and doxorubicin for 20 patients with cytology-proven malignant pleural effusion associated with lung cancer was evaluated . After complete removal of pleural effusion, OK-432 and 30 mg of doxorubicin were injected via an inserted chest tube . Treatment was terminated when the volume of daily drainage reached <200 mL . If the daily volume remained >200 mL, an additional OK-432 was administered every 3 days . In total, 16 patients (80%) revealed a complete response, two patients (10%) revealed a partial response, and no response was seen in two patients . Eighteen patients with complete or partial responses did not show subsequent reaccumulation of pleural effusion after pleurodesis . The chest tube remained in place for an average of 6.4 days, draining a mean of 2,854 mL . The main side-effects were fever and pain that were easily treated with nonsteroidal anti-inflammatory drugs . Pleurodesis using both OK-432 and doxorubicin showed high efficacy for controlling malignant pleural effusions caused by lung cancer.

J Biol Chem, 2004 Nov 12, 279(46), 47513 - 9 Epub 2004 Aug 25.
L-ficolin is a pattern recognition molecule specific for acetyl groups; Krarup A et al.; L-ficolin and H-ficolin are molecules of the innate immune system . Upon recognition of a suitable target they activate the complement system . The ligand recognition structure of ficolins is contained within a fibrinogen-like domain . We examined the selectivity of the ficolins through inhibiting the binding to bacteria or to beads coupled with N-acetylglucosamine . The binding of L-ficolin to Streptococcus pneumoniae 11F and the beads was inhibited by N-acetylated sugars and not by non-acetylated sugars . However, it was also inhibited by other acetylated compounds . Based on this selectivity L-ficolin is not easily defined as a lectin . The binding of H-ficolin to Aerococcus viridans was not inhibited by any of the sugars or other compounds examined . Based on the selectivity of L-ficolin we developed a new purification procedure involving affinity chromatography on N-acetylcysteine-derivatized Sepharose . The column was loaded in the presence of EDTA and high salt, and L-ficolin was eluted by decreasing the salt concentration . Further purification was achieved by ion exchange chromatography.

J Chemother, 2004 Jun, 16(3), 259 - 63
Pattern of antibiotic resistance of Streptococcus pneumoniae in a hospital in the Eastern Province of Saudi Arabia; Al-Tawfiq JA; The objective of the study was to evaluate the pattern of antibiotic resistance of Streptococcus pneumoniae at Saudi Aramco Medical Services Organization (SAMSO) in the Eastern Province of Saudi Arabia . We identified, retrospectively, S . pneumoniae isolates from January 1999 to December 2002 . Antimicrobial susceptibility and clinical data were collected and analyzed . A total of 162 isolates of S . pneumoniae were identified in the study period . Of these isolates, 94 (58%) isolates were obtained from out-patients and 68 (42%) were obtained from in-patients . Thirty-five percent of isolates were from blood, 46% from the respiratory tract, and the remainder were obtained from other sites . Of these isolates, 83 (51%) were penicillin-susceptible and the remaining 79 (48.8%) were not penicillin susceptible . High-level resistance to penicillin existed in 19.8% of the total isolates . Prevalence of resistance to erythromycin, tetracycline and trimethoprim-sulfamethoxazole was 25%, 29%, and 42% respectively . None of the isolates was resistant to vancomycin or ceftriaxone . However, 12% of the isolates showed multi-drug resistance . Streptococcus pneumoniae shows 19.8% high-level penicillin resistance and 12% multi-drug resistance . These findings call for wiser use of antibiotics.

J Chemother, 2004 Jun, 16(3), 248 - 54
An ex-vivo pharmacodynamic study comparing bactericidal activity of amoxicillin/sulbactam, azithromycin, doxycycline and levofloxacin against Streptococcus pneumoniae; Bantar C et al.; We designed a 4-way crossover, ex-vivo pharmacodynamic study to compare the bactericidal rate of amoxicillin/sulbactam (AMX-SUL), azithromycin (AZM), doxycycline (DOX) and levofloxacin (LVX) against Streptococcus pneumoniae ATCC 49619 . Six volunteers were randomized to receive alternatively a single tablet of the above drugs . Venous blood samples were obtained immediately before and at 2, 4 and 6 h after dose to perform time-kill studies and to determine antibiotic levels in serum . AMX-SUL was the only drug showing bactericidal activity with the sera obtained at every time after dose, as defined by a > or = 3-log10 cfu/ml decrease in the viable cell counts compared to the original inoculum after a 24-h incubation . AZM was only inhibitory at 2h after dose (i.e . a 1.3-log10 cfu/ml decrease in the viable cell counts) and proved bactericidal at 4 and 6 h post-dose . LVX proved bactericidal with the 2-h serum, was only inhibitory with the 4-h serum (e.g . a 1.5-log10 cfu/ml decrease) and was unable to avoid bacterial growth at 6 h post-dose . Bacterial growth was observed with DOX at every time after dose . This study may shed light on the understanding of breakthrough pneumococcal bacteremia during the course of oral therapy with AZM in patients with community-acquired nia (CAP), as well as the increasing treatment failures observed with LVX, and the selection of bacterial resistance during therapy reported with both drugs . It also provides the basis for a "warning signal" on the use of oral DOX and confirms the efficacy of AMX-SUL.

J Antimicrob Chemother, 2004 Oct, 54(4), 828 - 31 Epub 2004 Aug 25.
A rapid increase in macrolide resistance in Streptococcus pyogenes isolated in Poland during 1996-2002; Szczypa K et al.; OBJECTIVES: The aim of this study was to investigate Polish clinical isolates of Streptococcus pyogenes collected during a 7 year period using phenotypic and genotypic techniques . METHODS: A total of 816 isolates of S . pyogenes recovered from 33 medical centres in Poland were tested for their susceptibility to various antimicrobial agents . Erythromycin-resistant isolates were analysed by PFGE, multilocus sequence typing and emm typing methods . RESULTS: The tetracycline resistance rate was high (43%) among all S . pyogenes strains . Ninety-eight (12%) isolates were resistant to erythromycin . A low prevalence of the M phenotype (5.1%) associated with the presence of the mef(A) gene was found . All the isolates of the iMLSB phenotype harboured the erm(TR) gene . Out of the cMLSB isolates, 71.4% and 28.6% carried erm(TR) and erm(B), respectively . All isolates with erm(B) were resistant to telithromycin . PFGE analysis discerned 13 different patterns, A-N, with two predominant PFGE profiles--A (41 isolates) and B (25 isolates)--that in multilocus sequence typing corresponded, respectively, to a novel sequence type (ST) 367 and ST63 . Overall, the representatives of these clones accounted for >90% of isolates of the iMLSB phenotype . CONCLUSIONS: A significant increase in erythromycin resistance was observed among clinical S . pyogenes collected in Poland over a 7 year period driven by the spread of two epidemic clones.

J Dairy Sci, 2004 Jul, 87(7), 2062 - 72
Duration of infection and strain variation in Streptococcus uberis isolated from cows' milk; McDougall S et al.; The duration of infection and pulsed-field gel electrophoresis (PFGE) types of bovine intramammary Streptococcus uberis isolates were examined . Milk samples were collected in duplicate from all 4 glands of 503 cows from 5 herds within 1 to 3 d of parturition and from 113 cows with clinical mastitis in the same herds throughout lactation . Glands from which S . uberis was isolated were resampled at 28-d intervals.The prevalence of S . uberis was 12% for cows around parturition, and the median duration of infection was 16 d . Cows >2 yr old had a longer duration of infection than 2 yr old cows, and duration varied among herds . A total of 173 different PFGE types were identified from a total of 234 S . uberis isolates . Each farm had a unique set of PFGE types . Only 3 PFGE types were common to each of 3 pairs of cows, and these occurred on the same farm . Where S . uberis was isolated on more than one occasion from a gland, only 55% of the PFGE types were the same across time . For cows with multiple glands infected, only one-half (9 of 18) had the same PFGE type in more than one gland . No predominant PFGE type was identified in any herd.It is concluded that there was wide heterogeneity of PFGE types, that the environment rather than other cows was the likely source of S . uberis infections, and that glands may be infected with multiple S . uberis PFGE types over a lactation.

Antimicrob Agents Chemother, 2004 Sep, 48(9), 3636 - 9
Invasive Streptococcus pneumoniae in France: antimicrobial resistance, serotype, and molecular epidemiology findings from a monthly national study in 2000 to 2002; Decousser JW et al.; A study of 257 French invasive pneumococci isolated between 2000 and 2002 showed high rates of nonsusceptibility to penicillin and macrolides (50%), contrasting with a low frequency of resistance to amoxicillin or levofloxacin (<1%) and tolerance to vancomycin (0%) . The genetic homogeneity of some serogroups, including serogroup 1, enhanced the risk of epidemiological changes.

Antimicrob Agents Chemother, 2004 Sep, 48(9), 3630 - 5
Designing fluoroquinolone breakpoints for Streptococcus pneumoniae by using genetics instead of pharmacokinetics-pharmacodynamics; Smith HJ et al.; We determined fluoroquinolone microbiological resistance breakpoints for Streptococcus pneumoniae by using genetic instead of pharmacokinetic-pharmacodynamic parameters . The proposed microbiological breakpoints define resistance as the MIC at which >50% of the isolates carry quinolone resistance-determining region mutations and/or, if data are available, when Monte Carlo simulations demonstrate a <90% chance of bacteriological eradication . The proposed microbiological resistant breakpoints are as follows (in micrograms per milliliter): gatifloxacin, >0.25; gemifloxacin, >0.03; levofloxacin, >1; and moxifloxacin, >0.12 . Monte Carlo simulations of the once daily 400-mg doses of gatifloxacin and 750-mg doses levofloxacin demonstrated a high level of target attainment (free-drug area under the concentration-time curve from 0 to 24 h/MIC ratio of 30) by using these new genetically derived breakpoints.

Antimicrob Agents Chemother, 2004 Sep, 48(9), 3563 - 6
An internationally spread clone of Streptococcus pneumoniae evolves from low-level to higher-level penicillin resistance by uptake of penicillin-binding protein gene fragments from nonencapsulated pneumococci; Hauser C et al.; Low-level penicillin resistance in an international Streptococcus pneumoniae serotype 19F clone emerging in Switzerland was characterized by mutations in the penicillin-binding protein PBP2x . Some isolates of this clone had evolved to higher resistance levels (penicillin MICs of 0.094 and 1 microg/ml), probably by acquisition of pbp2x fragments from local nonencapsulated pneumococci.

Antimicrob Agents Chemother, 2004 Sep, 48(9), 3559 - 62
Emergence of macrolide-resistant Streptococcus pyogenes strains in French children; Bingen E et al.; We studied the antimicrobial susceptibility of 322 Streptococcus pyogenes throat isolates from French children and their serotype and genomic diversity . A total of 22.4% were erythromycin resistant, and 69.4, 4.2, and 26.4% of these isolates harbored ermB, ermA, and mefA, respectively . Increasing resistance in France is mainly associated with a few emm type 28 clones.

Antimicrob Agents Chemother, 2004 Sep, 48(9), 3491 - 7
Levofloxacin-resistant invasive Streptococcus pneumoniae in the United States: evidence for clonal spread and the impact of conjugate pneumococcal vaccine; Pletz MW et al.; The emergence of fluoroquinolone resistance in sterile-site isolates of Streptococcus pneumoniae is documented in this study characterizing all invasive levofloxacin-resistant (MIC, > or = 8 mg/liter) S . pneumoniae isolates (n = 50) obtained from the Centers for Disease Control and Prevention Active Bacterial Core Surveillance from 1998 to 2002 . Resistance among all isolates increased from 0.1% in 1998 to 0.6% in 2001 (P = 0.008) but decreased to 0.4% in 2002, while resistance among vaccine serotypes continued to increase from 0.3% in 1998 to 1.0% in 2002, suggesting that fluoroquinolones continue to exert selective pressure on these vaccine serotypes . Only 22% of resistant isolates were not covered by the conjugate vaccine serogroups . Multilocus sequence typing revealed that 58% of resistant strains were related to five international clones identified by the Pneumococcal Molecular Epidemiology Network, with the Spain(23F)-1 clone being most frequent (16% of all isolates) . Thirty-six percent of the isolates were coresistant to penicillin, 44% were coresistant to macrolides, and 28% were multiresistant to penicillin, macrolides, and fluoroquinolones . Fifty percent of the isolates were resistant to any three drug classes . Ninety-four percent of the isolates had multiple mutations in the quinolone resistance-determining regions of the gyrA, gyrB, parC, and parE genes . In 16% of the isolates, there was evidence of an active efflux mechanism . An unusual isolate was found that showed only a single parE mutation and for which the ciprofloxacin MIC was lower (2 mg/liter) than that of levofloxacin (8 mg/liter) . Our results suggest that invasive pneumococcal isolates resistant to levofloxacin in the United States show considerable evidence of multiple resistance and of clonal spread.

Antimicrob Agents Chemother, 2004 Sep, 48(9), 3305 - 11
In vitro antimicrobial susceptibilities of Streptococcus pneumoniae clinical isolates obtained in Canada in 2002; Powis J et al.; Empirical treatment is best guided by current surveillance of local resistance patterns . The goal of this study is to characterize the prevalence of antimicrobial nonsusceptibility within pneumococcal isolates from Canada . The Canadian Bacterial Surveillance Network is comprised of laboratories from across Canada . Laboratories collected a defined number of consecutive clinical and all sterile site isolates of S . pneumoniae in 2002 . In vitro susceptibility testing was performed by broth microdilution with NCCLS guidelines . Rates of nonsusceptibility were compared to previously published reports from the same network . A total of 2,539 isolates were tested . Penicillin nonsusceptibility increased to 15% (8.5% intermediate, 6.5% resistant) compared to 12.4% in 2000 (P < or = 0.025, chi(2)) . Only 32 (1.3%) isolates had an amoxicillin MIC of > or = 4 microg/ml and only 2 of 32 cerebrospinal fluid isolates had an intermediate susceptibility to ceftriaxone by meningeal interpretive criteria (MIC = 1 microg/ml) . A total of 354 (13.9%) isolates were macrolide nonsusceptible (46.3% MLS(B), 56.7% M phenotype), increasing from 11.4% in 2000 (P < or = 0.0075, chi(2)) . Only 13 (<1%) isolates had a telithromycin MIC of >1 microg/ml . Ciprofloxacin nonsusceptibility (defined as an MIC of > or = 4 microg/ml) increased to 2.7% compared to 1.4% in 2000 (P < or = 0.0025, chi(2)) and was primarily found in persons > or =18 years old (98.5%) . Nonsusceptibility to penicillin, macrolides, and fluoroquinolones is increasing in Canada . Nonsusceptibility to amoxicillin and ceftriaxone remains uncommon . Newer antimicrobials such as telithromycin and respiratory fluoroquinolones have excellent in vitro activity.

Prev Vet Med, 2004 Jul 16, 64(2-4), 101 - 12
Udder health in dairy cattle infected with Neospora caninum; Peregrine AS et al.; Blood samples were collected from 3449 cows on 57 representative Ontario dairy herds during the summer of 1998 and analysed for antibody to Neospora caninum using an ELISA . Forty-eight herds (2742 cattle) contained at least one N . caninum-seropositive animal . Two composite milk samples were collected from all cattle: the first on the day of blood collection and the second 68 to 365 days later . All milk samples were submitted for bacteriological culture . Ontario Dairy Herd Improvement Corporation (DHI) data were available for 3162 cattle in the 57 herds at the time of bleeding . Furthermore, complete DHI data were available for 1658 cattle that were culled between 12 and 24 months following blood collection . Using a standardised ELISA sample-to-positive (S/P) cut-off of > or = 0.45, the corrected seroprevalence was 8.2% overall and 10.1% within seropositive herds . At blood collection the odds of N . caninum-seropositive cows having a high linear score (> or = 4.0; equivalent to a somatic cell count > or = 200,000 cells/ml) was 27% less than for seronegative animals . Similarly, at the time of culling, the odds of having a high linear score was 22% less in N . caninum-seropositive cattle . Overall, linear score was lower in N . caninum-seropositive cattle at culling . After controlling for herd, parity, days in milk, and the interval between collection of milk samples, the odds of N . caninum-seropositive cattle testing positive for an environmental pathogen (i.e . environmental Streptococcus species and coliforms) on the second milk sample was 56% less than for seronegative animals . The odds were 83% less at a higher ELISA S/P cut-off of > or = 0.70 . Finally, the odds of N . caninum-seropositive cattle developing a new infection with a major pathogen (environmental or contagious) were 60% less than seronegative cows using the higher ELISA S/P cut-off.

Int J Antimicrob Agents, 2004 Sep, 24(3), 290 - 3
Antimicrobial susceptibility and macrolide resistance genes in Streptococcus pyogenes collected in Austria and Hungary; Gattringer R et al.; A total of 341 clinical isolates of Streptococcus pyogenes from Vienna, Austria and three Hungarian cities were tested for susceptibility to four macrolides and 12 other antibiotics . All isolates were fully susceptible to penicillin and the other beta-lactams tested . A high level of tetracycline resistance was found in Austria (26.7%) and in Hungary (30.5%) . The rate of resistance to erythromycin, clarithromycin and azithromycin was 4.7% in Vienna and 3.7% in the Hungarian communities . In both countries, the MIC(90) values of erythromycin and clarithromycin were 0.12 mg/L and the MIC(90) of josamycin was 0.5mg/L . The M phenotype of resistance conferred by the mefA genes was predominant (n = 9) among the macrolide-resistant isolates (n = 14).

Int J Antimicrob Agents, 2004 Sep, 24(3), 254 - 60
The post-antibiotic effects of rokitamycin (a 16-membered ring macrolide) on susceptible and erythromycin-resistant strains of Streptococcus pyogenes; Braga PC et al.; The post-antibiotic effects (PAEs) on susceptible and erythromycin-resistant strains of Streptococcus pyogenes (M phenotype and inducibly resistant) of rokitamycin and erythromycin were investigated in vitro using microbiological impedance measurement . Exposure of susceptible S . pyogenes strains to 1/4, 1/2, 1 and 2 MIC erythromycin and rokitamycin resulted in PAEs of rokitamycin in the same order of magnitude as those of erythromycin and that were dose dependent . The duration of rokitamycin PAEs in erythromycin-resistant S . pyogenes strains (M phenotype and those with inducible resistance) were comparable with those observed in susceptible strains . This was not the case for erythromycin . The investigation showed that a 16-membered ring macrolide such as rokitamycin has different PAEs from those of a 14-membered ring macrolide such as erythromycin . They also indicated that, as the PAEs of rokitamycin on the M phenotype and inducible resistant strains were comparable with those on susceptible strains, no re-evaluation of therapeutic dosing regimens was required.

Int J Antimicrob Agents, 2004 Sep, 24(3), 199 - 204
Antibiotic policies in Central Eastern Europe; Cizman M et al.; To assess the antibiotic policies in Central Eastern European (CEE) countries, a questionnaire on the prevalence of resistance, antibiotic consumption data for ambulatory and hospital care and antibiotic policies, was mailed to national representatives . Data on antibiotic resistance and consumption of antibiotics at national levels are limited and vary considerably among countries . The importance of surveillance data in altering perceptions of the prevalence of resistance is shown by the comparison of surveillance data and interview data . Interview data without surveillance data produced the widest range of estimates of the prevalence of resistance in streptococcus pneumonia -5% in Lithuania and 82% in Belarus . The average consumption of antibiotics in ambulatory care in eight CEE countries in 2001 was 19.35 defined daily doses (DDD)/1000 inhabitants per day, (range 13.1 - 24.8 DDD) and in hospitals in six CEE countries was 2.2 DDD/1000 inhabitants per day (range 1.3-4.5) . Over the counter sales of antibiotics are available in some countries . Antibiotic policy interventions do not exist or only apply to specific problems or interventions . Better implementation of antibiotic interventions and education on antibiotic use should be a high priority in this region . An effective strategy requires close co-operation, consultations and partnership at national and international level in particular, via existing international organisations.

Ann Fr Anesth Reanim, 2004 Jul, 23(7), 737 - 9
{Secondary Streptococcus pyogenes peritonitis following necrotizing fasciitis}; Gindre S et al.; We report the case of a 66-year-old woman with diabetes mellitus and disseminated lupus treated with immunosupressive drug . She was admitted for an inflammatory oedema of the right lower limb associated to diffuse abdominal pain and vomiting . The occurrence of septic shock with multiple organ failure and surgical abdominal picture led us to perform urgent laparotomy without taking in account the evolutive signs of cutaneous lesions i.e . purpuric elements and haemorrhagic phlycthena . The abdominal cavity exploration showed peritonitis without digestive tracts perforation . The patient died few hours after surgical procedure . All bacteriological samples i.e . peritoneal effusion, blood cultures and phlycthena liquid were positive for Streptocoque pyogenes (group A) and peritonitis was considered to be related to haematogen diffusion from rapid course necrotizing fasciitis.

Biochem J, 2004 Dec 15, 384(Pt 3), 619 - 27
UMP kinase from Streptococcus pneumoniae: evidence for co-operative ATP binding and allosteric regulation; Fassy F et al.; UMP kinase catalyses the phosphorylation of UMP by ATP to yield UDP and ADP . In prokaryotes, the reaction is carried out by a hexameric enzyme, activated by GTP and inhibited by UTP . In the present study, Streptococcus pneumoniae UMP kinase was studied as a target for antibacterial research and its interest was confirmed by the demonstration of the essentiality of the gene for cell growth . In the presence of MnCl2 or MgCl2, the saturation kinetics of recombinant purified UMP kinase was hyperbolic for UMP (K(m)=0.1 mM) and sigmoidal for ATP (the substrate concentration at half-saturation S0.5=9.4+/-0.7 mM and n=1.9+/-0.1 in the presence of MgCl2) . GTP increased the affinity for ATP and decreased the Hill coefficient (n) . UTP decreased the affinity for ATP and only slightly increased the Hill coefficient . The kcat (175+/-13 s(-1) in the presence of MgCl2) was not affected by the addition of GTP or UTP, whose binding site was shown to be different from the active site . The hydrodynamic radius of the protein similarly decreased in the presence of ATP or GTP . There was a shift in the pH dependence of the activity when the ATP concentration was switched from low to high . These results support the hypothesis of an allosteric transition from a conformation with low affinity for ATP to a form with high affinity, which would be induced by the presence of ATP or GTP.

Med Klin (Munich), 2004 Jul 15, 99(7), 391 - 5
{Bronchobiliary fistula associated with combined abscess of lung and liver}; Frobe M et al.; HISTORY AND PHYSICAL EXAMINATION: A 43-year-old, cachectic, alcohol-addicted patient was admitted to the hospital due to hemoptysis and fever of up to 40 degrees C for the last 4 days . Physical examination revealed pleural rubs in the right lower lung and a diffuse pain in the right upper quadrant of the abdomen . The right upper quadrant of the abdomen also showed scars from several surgical interventions on the small intestine, the liver and the biliary tract and deformed caudal ribs due to an accident 23 years earlier . DIAGNOSTICS, THERAPY, AND CLINICAL COURSE: Chest X-ray, ultrasound and computed tomography (CT) showed abscess cavities in lung and liver communicating through the diaphragm . Under antibiotic therapy the abscess was drained . Cultures showed Klebsiella pneumoniae and Streptococcus viridans . Continuous lavage of the abscess cavities and antibiotic therapy led to an improvement in parameters of inflammation and clinical status . Imaging after 10 days of treatment showed a contrast enrichment in the abscess cavities and a bronchobiliary fistula accounting for temporary biliptysis . The drainage was removed after 29 days, when similar imaging revealed no further sign of an abscess cavity and a previous CT follow-up had proven a distinct decrease of the abscesses . CONCLUSION: Bronchobiliary fistulas are very rare . In most cases they are caused by hepatic or subphrenic abscesses, resulting from different conditions . The development of an bronchobiliary fistula originating from a Klebsiella pneumoniae pneumonia, as indicated by this report, has not been described so far . In the patient presented here, treatment was achieved due to continuous drainage despite the large extent of the abscess.

J Biol Chem, 2004 Oct 29, 279(44), 45990 - 7 Epub 2004 Aug 18.
L-Ascorbic acid 6-hexadecanoate, a potent hyaluronidase inhibitor . X-ray structure and molecular modeling of enzyme-inhibitor complexes; Botzki A et al.; Hyaluronidases are enzymes that degrade hyaluronan, an important component of the extracellular matrix . The mammalian hyaluronidases are considered to be involved in many (patho)physiological processes like fertilization, tumor growth, and metastasis . Bacterial hyaluronidases, also termed hyaluronate lyases, contribute to the spreading of microorganisms in tissues . Such roles for hyaluronidases suggest that inhibitors could be useful pharmacological tools . Potent and selective inhibitors are not known to date, although L-ascorbic acid has been reported to be a weak inhibitor of Streptococcus pneumoniae hyaluronate lyase (SpnHL) . The x-ray structure of SpnHL complexed with L-ascorbic acid has been elucidated suggesting that additional hydrophobic interactions might increase inhibitory activity . Here we show that L-ascorbic acid 6-hexadecanoate (Vcpal) is a potent inhibitor of both streptococcal and bovine testicular hyaluronidase (BTH) . Vcpal showed strong inhibition of Streptococcus agalactiae hyaluronate lyase with an IC(50) of 4 microM and weaker inhibition of SpnHL and BTH with IC(50) values of 100 and 56 microM, respectively . To date, Vcpal has proved to be one of the most potent inhibitors of hyaluronidase . We also determined the x-ray structure of the SpnHL-Vcpal complex and confirmed the hypothesis that additional hydrophobic interactions with Phe-343, His-399, and Thr-400 in the active site led to increased inhibition . A homology structural model of BTH was also generated to suggest binding modes of Vcpal to this hyaluronidase . The long alkyl chain seemed to interact with an extended, hydrophobic channel formed by mostly conserved amino acids Ala-84, Leu-91, Tyr-93, Tyr-220, and Leu-344 in BTH.

Infect Immun, 2004 Sep, 72(9), 5475 - 7
Characterization of binding of Streptococcus oralis glyceraldehyde-3-phosphate dehydrogenase to Porphyromonas gingivalis major fimbriae; Maeda K et al.; Binding of Streptococcus oralis glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to Porphyromonas gingivalis fimbriae was characterized via a biomolecular interaction analysis system . The interaction was specific, and the association constant value was 4.34 x 10(7) M(-1), suggesting that S . oralis GAPDH functions as a dominant receptor for P . gingivalis and contributes to P . gingivalis colonization.

Infect Immun, 2004 Sep, 72(9), 5322 - 30
Encapsulated Streptococcus suis inhibits activation of signaling pathways involved in phagocytosis; Segura M et al.; Streptococcus suis capsular type 2 is an important zoonotic agent of meningitis . Previous studies reported that, in contrast to nonencapsulated mutants, encapsulated S . suis is able to resist phagocytosis . However, the mechanisms by which S . suis avoids phagocytosis are unknown . To elucidate the signaling pathway(s) involved in S . suis antiphagocytosis, we compared the ability of an encapsulated strain and its nonencapsulated mutant to induce the activation of Akt and protein kinase C (PKC), which are downstream kinases of the phosphatidylinositol 3-kinase (PI-3K) pathway, known to be involved in the phagocytosis processes . The results demonstrated high levels of Akt and PKCalpha phosphorylation after infection of J774 macrophages with the nonencapsulated mutant, whereas the encapsulated strain showed reduced activation of PI-3K/Akt/PKCalpha signaling pathway, as well as several protein tyrosine events . These results correlated with the number of intracellular bacteria . Macrophages pretreated with specific PI-3K or PKC inhibitors showed reduced levels of Akt and PKCalpha phosphorylation, resulting in 50% reduction of phagocytosis . The role of phosphatases in the antiphagocytic mechanisms was evaluated by using phosphatase inhibitors, as well as SHP-1-deficient macrophages . Only in the absence of SHP-1 did the phagocytosis of encapsulated S . suis significantly increase, leading to Akt phosphorylation levels similar to those observed with the nonencapsulated strain, indicating activation of this important SH2 domain-containing tyrosine phosphatase by encapsulated S . suis . Finally, when purified S . suis capsular polysaccharide (CPS) was added to macrophages, no phosphorylation events were observed . In addition, CPS and encapsulated S . suis were able to inhibit the uptake of the nonencapsulated mutant . These results suggest the importance of CPS in the mechanisms, whereby S . suis downmodulates phagocytosis.

Infect Immun, 2004 Sep, 72(9), 5031 - 40
PspA protects Streptococcus pneumoniae from killing by apolactoferrin, and antibody to PspA enhances killing of pneumococci by apolactoferrin {corrected}; Shaper M et al.; Lactoferrin is an important component of innate immunity through its sequestration of iron, bactericidal activity, and immune modulatory activity . Apolactoferrin (ALF) is the iron-depleted form of lactoferrin and is bactericidal against pneumococci and several other species of bacteria . We observed that lactoferricin (LFN), an 11-amino-acid peptide from the N terminus of lactoferrin, is bactericidal for Streptococcus pneumoniae . Strains of S . pneumoniae varied in their susceptibility to ALF . Lactoferrin is bound to the pneumococcal surface by pneumococcal surface protein A (PspA) . Using mutant PspA(-) pneumococci of four different strains, we observed that PspA offers significant protection against killing by ALF . Knockout mutations in genes for two other choline-binding proteins (PspC and PcpA) did not affect killing by ALF . PspA did not have to be attached to the bacterial surface to inhibit killing, because the soluble recombinant N-terminal half of PspA could prevent killing by both ALF and LFN . An 11-amino-acid fragment of PspA was also able to reduce the killing by LFN . Antibody to PspA enhanced killing by lactoferrin . These findings suggested that the binding of ALF to PspA probably blocks the active site(s) of ALF that is responsible for killing.

Infect Immun, 2004 Sep, 72(9), 4940 - 7
Streptococcus pneumoniae-induced caspase 6-dependent apoptosis in lung epithelium; Schmeck B et al.; Streptococcus pneumoniae is the major pathogen of community-acquired pneumonia and one of the most common causes of death due to infectious diseases in industrialized countries . Lung epithelium lines the airways and constitutes the first line of innate defense against respiratory pathogens . Little is known about the molecular interaction of pneumococci with lung epithelial cells . Apoptosis of lung epithelium is involved in some bacterial lung infections . In this study different pneumococcal strains specifically induced either apoptotic or necrotic death of human alveolar and bronchial epithelial cells . Pneumococcus-induced apoptosis did not depend on the virulence factors pneumolysin and H(2)O(2) . Apoptotic cells showed increased activity of caspases 6, 8, and 9 but not increased activity of caspase 3 . Moreover, programmed cell death could be strongly reduced by a caspase 6 inhibitor and a pan-caspase inhibitor . Inhibitors of calpain and chymotrypsin- and trypsin-like proteases also reduced pneumococcus-induced apoptosis . Furthermore, pneumococcus-infected human alveolar epithelial cells showed Bid cleavage and reduced levels of Bcl2 and Bax . Overexpression of Bcl2 in these cells reduced apoptosis significantly . Thus, pneumococci induced apoptosis of human alveolar and bronchial epithelial cells . Programmed cell death was executed by caspase 6 and noncaspase proteases, but not by caspase 3, and could be blocked by overexpression of Bcl2.

Int J Obstet Anesth, 1997 Apr, 6(2), 118 - 21
Epidural abscess in association with obstetric epidural analgesia; Dhillon AR et al.; A 31-year-old woman gravida 4 para 2 who had received epidural analgesia during labour (duration of catheterization 6.5 h) was readmitted 8 days later with a complaint of flu-like symptoms, severe backache and numbness of her thighs . She had a sensory deficit from T4 to L1 and was unable to stand without support . The severe backache prevented adequate assessment of motor function . An MRI scan suggested an epidural mass . Surgical decompression by hemilaminectomy was carried out within 24 h of admission and revealed an epidural abscess . Culture of the drained pus grew Streptococcus pneumoniae . She made a complete recovery and was discharged home on the tenth day . This case illustrates the problem of diagnosing serious postnatal problems that arise following the now fashionable early discharge from hospital.

Int J Obstet Anesth, 1999 Apr, 8(2), 125 - 30
Necrotising fasciitis and group A streptococcus toxic shock-like syndrome in pregnancy: treatment with plasmapheresis and immunoglobulin; Simmonds M; A 30-year-old woman at 25 weeks gestation presented to the labour ward complaining of abdominal pain and a painful bruise in her right groin . Over the course of several hours, she developed rapidly spreading necrotising fasciitis of the right thigh . She required emergency radical debridement of the thigh and caesarean delivery of a dead fetus . She was admitted to the intensive care unit (ICU) with septic shock, where she received ventilatory and inotropic support . Streptococcus pyogenes was isolated from the infected tissue and a diagnosis of group A streptococcal toxic shock-like syndrome (GAS TS-LS) was confirmed . Following acute and rapid haemodynamic deterioration, plasmapheresis was given for 6 days, after which the patient's general condition improved and vasoconstrictor requirement was significantly reduced . Subsequently, immunoglobulin was given intravenously for thrombocytopenia, following which the platelet count steadily improved . Despite the development of acute renal failure, acute respiratory distress syndrome and a left hemiplegia, the patient made a remarkable recovery . She was later transferred to a plastic surgical unit for split skin-grafting . The importance of early diagnosis and aggressive treatment of GAS TS-LS is emphasized and the place of plasmapheresis and intravenous immunoglobulin therapy in this condition is discussed.

J Bacteriol, 2004 Sep, 186(17), 5865 - 75
A novel sortase, SrtC2, from Streptococcus pyogenes anchors a surface protein containing a QVPTGV motif to the cell wall; Barnett TC et al.; The important human pathogen Streptococcus pyogenes (group A streptococcus GAS), requires several surface proteins to interact with its human host . Many of these are covalently linked by a sortase enzyme to the cell wall via a C-terminal LPXTG motif . This motif is followed by a hydrophobic region and charged C terminus, which are thought to retard the protein in the cell membrane to facilitate recognition by the membrane-localized sortase . Previously, we identified two sortase enzymes in GAS . SrtA is found in all GAS strains and anchors most proteins containing LPXTG, while SrtB is present only in some strains and anchors a subset of LPXTG-containing proteins . We now report the presence of a third sortase in most strains of GAS, SrtC . We show that SrtC mediates attachment of a protein with a QVPTGV motif preceding a hydrophobic region and charged tail . We also demonstrate that the QVPTGV sequence is a substrate for anchoring of this protein by SrtC . Furthermore, replacing this motif with LPSTGE, found in the SrtA-anchored M protein of GAS, leads to SrtA-dependent secretion of the protein but does not lead to its anchoring by SrtA . We conclude that srtC encodes a novel sortase that anchors a protein containing a QVPTGV motif to the surface of GAS.

J Antimicrob Chemother, 2004 Sep, 54(3), 640 - 7 Epub 2004 Aug 18.
In vivo pharmacodynamic efficacy of gatifloxacin against Streptococcus pneumoniae in an experimental model of pneumonia: impact of the low levels of fluoroquinolone resistance on the enrichment of resistant mutants; Croisier D et al.; OBJECTIVES: To investigate the impact of low levels of fluoroquinolone resistance on the emergence of resistant mutants, we examined the mutant selection window (MSW) hypothesis in experimental pneumonia in rabbits infected with pneumococci with various susceptibility levels to fluoroquinolones and treated with gatifloxacin using a human-like regimen (equivalent to 400 mg once daily) . The MSW corresponds to the range of concentrations between the minimal inhibitory concentration (MIC) and the mutant prevention concentration (MPC), which is the antibiotic concentration that prevents selection of resistant mutants . MATERIALS AND METHODS: Five pneumococcal strains were tested and were defined as follows {MIC of ciprofloxacin (mg/L)/MIC of gatifloxacin (mg/L)/MPC of gatifloxacin (mg/L)/involved quinolone resistance mechanisms}: strain 16089=0.5/0.25/0.25/wild-type; strain MS1A=2/0.5/1/efflux; strain MS2A=8/1/8/parC S79F; strain MR3B4=10/1/8/parC S79T; strain Gyr-1207=6/4/4/gyrA S81F . RESULTS: A 48 h human-like treatment with gatifloxacin was significantly bactericidal on pneumonia induced by strain 16089 ( > 6 log(10) killing) as well as the efflux derivative strain MS1A ( > 5 log(10) killing) . However, a small number of parC-gyrA mutants were recovered in 26% of the animals infected with this efflux strain . As expected, no decrease in viable bacteria counts was observed when pneumonia was induced by the gyrA resistant strain . In contrast, because of the enrichment of highly resistant mutants in 100% of the animals, no significant bacterial reduction was observed after treatment of pneumonia induced by the two susceptible parC mutated strains . A classification and regression tree (CART) analysis identified T(MSW) (percentage of the time during which gatifloxacin serum concentrations are inside the MSW) and AUC(MSW) (area under curve between MIC and MPC values) as the best parameters associated with the enrichment of resistant pneumococci . CONCLUSIONS: This study shows that the acquisition of a low level of fluoroquinolone resistance (especially a parC mutation and to a lesser extent an efflux mechanism) is associated with a clearly lower potential for preventing resistance development . These data support the concept that resistant mutants are selectively enriched when antibiotic concentrations fall inside the mutant selection window and suggest that in vivo dynamic models have to be used to predict the relative abilities of quinolones to prevent mutant selection.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2004 Aug, 98(2), 184 - 8
Relationship between oral motor dysfunction and oral bacteria in bedridden elderly; Tada A et al.; OBJECTIVE: The purpose of this study was to analyze the relationship between oral bacterial colonization and oral motor dysfunction . STUDY DESIGN: Oral motor dysfunction (swallowing and speech disorders) and detection of oral bacterial species from dental plaque in 55 elderly persons who had remained hospitalized for more than 3 months were investigated and statistically analyzed . RESULTS: The detection rates of methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Streptococcus agalactiae, and Stenotrophomonas maltophilia were significantly higher in subjects with than in those without a swallowing disorder . A similar result was found with regard to the presence of a speech disorder . About half of subjects who had oral motor dysfunction and hypoalbuminemia had colonization by MRSA and/or Pseudomonas aeruginosa . CONCLUSION: These results suggest that the combination of oral motor dysfunction and hypoalbminemia elevated the risk of opportunistic microorganisms colonization in the oral cavity of elderly patients hospitalized over the long term.

J Allergy Clin Immunol, 2004 Aug, 114(2), 328 - 34
Antigen stimulation of TH2 cells augments acute bacterial sinusitis in mice; Yu X et al.; BACKGROUND: Previously, we showed that an ongoing nasal allergic response augmented bacterial sinusitis in mice . In those experiments mice were sensitized to ovalbumin (OVA) by means of intraperitoneal injections of OVA-alum and then exposed to OVA intranasally before being infected with Streptococcus pneumoniae . OBJECTIVE: We sought to study the importance of TH2 cells and to eliminate potential alum effects . METHODS: In this study we sensitized mice by adoptively transferring OVA-specific TH2- or TH1-skewed cells . RESULTS: TH2 passive sensitization followed by intranasal OVA showed a robust local eosinophilic response (5-fold increase) compared with that seen in mice with only TH2 passive sensitization alone (P <.001) . Mice with TH2 passive sensitization and intranasal OVA exposure followed by infection showed an increase in the number of recovered S pneumoniae (P <.05) and an increase in sinus inflammation compared with that seen in those with infection alone (P <.01) . In contrast, mice passively sensitized with TH1 followed by intranasal OVA exposure and infection showed no significant increase in the recovery of S pneumoniae and sinus inflammation compared with those with infection alone . CONCLUSIONS: These data support the importance of antigen-stimulated TH2 cells in the augmented response to infection in allergic mice . Whether the increased infection is related to the direct effect of TH2 cells and their cytokines or subsequent recruitment of other cells, such as eosinophils, will be determined in further studies.

Vaccine, 2004 Sep 9, 22(27-28), 3769 - 73
Efficacy of Streptococcus agalactiae (group B) vaccine in tilapia (Oreochromis niloticus) by intraperitoneal and bath immersion administration; Evans JJ et al.; We evaluated the effectiveness of a Streptococcus agalactiae vaccine in tilapia (Oreochromis niloticus) for prevention of streptococcal disease . The vaccine was prepared from formalin-killed cells and concentrated extracellular products (greater than 3 kDa) of a single isolate of S . agalactiae (ARS-KU-MU-11B) . Intraperitoneal (IP) and bath immersion (BI) vaccine trials were conducted at two temperatures, 32 and 26 degrees C, and mean fish weights, 5 and 30 g . Control tilapia were injected with tryptic soy broth . Thirty gram tilapia vaccinated and challenged by IP injection with 1.5 x 10(4) colony-forming units (CFU)/fish of Streptococcus agalactiae at 30 days post-immunization had a relative percent survival (RPS) of 80 . Smaller tilapia vaccinated and challenged under similar conditions had an RPS of 25 . An RPS of zero was noted in 30 g fish IP vaccinated with Streptococcus iniae and IP challenged with S . agalactiae . The 5 and 30 g tilapia bath immunized with S . agalactiae and IP challenged with 3.6 x 10(5) and 1.7 x 10(6) CFU/fish of S . agalactiae had RPS values of 34 . Intraperitoneal administration of the vaccine provided efficacious protection only in the 30 g tilapia regardless of whether the fish were immunized and challenged at 26 or 32 degrees C . Bath immunization of both 5 and 30 g tilapia resulted in RPS values that were two times lower than those achieved with IP vaccination . The results of this study suggest that there is a lack of cross-protection of S . iniae bacterins against S . agalactiae challenge . Protection against S . agalactiae infection is, however, provided through vaccination with a S . agalactiae modified bacterin vaccine.

Am J Chin Med, 2004, 32(2), 221 - 34
Immunomodulating effects of "tien-hsien liquid" on peripheral blood mononuclear cells and T-lymphocytes from patients with recurrent aphthous ulcerations; Sun A et al.; Recurrent aphthous ulcerations (RAU) represent a common oral mucosal disease with altered humoral and cellular immunities . In our institution, an immunomodulating agent, levamisole, is used to treat RAU with satisfactory therapeutic effect . Tien-Hsien liquid (THL) is an extract of Chinese medicinal herbs with immunomodulating effects . To test whether THL has immunomodulating effects on antigen-stimulated proliferation response (PR) of peripheral blood mononuclear cells (PBMC) and T-cells isolated from RAU patients and to test whether THL is a potential drug for treating RAU, PBMC or T-cells isolated from RAU patients were incubated with lipopolysaccharides (LPS) from Escherica coli, phytohemagglutinin (PHA), staphylococcal enterotoxin B (SEB), glutaraldehyde-inactivated tetanus toxoid (TT), glucosyltransferase D (GtfD), or antigens of Streptococcus mutans in the presence or absence of THL . We found that THL significantly increased the LPS-stimulated PR of PBMC from active RAU patients, the GtfD-stimulated PR of PBMC and of T-cells from inactive RAU patients, and the S . mutans-stimulated PR of PBMC from inactive RAU patients . However, THL could also significantly reduce the SEB-stimulated PR of PBMC and of T-cells from active RAU patients and S . mutans-stimulated PR of T-cells from active RAU patients . These results suggest that THL can modulate the antigen-stimulated PR of PBMC and T-cells from RAU patients . Therefore, it may be a potential immunoceutical agent for treatment of RAU.

Microbes Infect, 2004 Aug, 6(10), 926 - 8
Inhibition of Streptococcus pyogenes adherence to HaCaT cells by a peptide corresponding to the streptococcal fibronectin-binding protein, SfbI, is strain dependent; Edwards ML et al.; Streptococcus pyogenes (group A streptococcus, GAS) is a human-specific pathogen, which employs a large number of adhesins for colonization . Fibronectin-binding proteins (FBPs) play a major role in GAS adhesion to host cells . SfbI, a major streptococcal FBP, has been well studied . A peptide (peptide-MSG) based on this adhesin inhibits fibronectin (Fn)-binding by the pathogen . To test whether this peptide also inhibits adherence of GAS to host cells, adhesion assays were performed with strains possessing different combinations of genes for three distinct FBPs . Peptide-MSG inhibited GAS adherence to human keratinocytes (HaCaT) in a strain dependent manner . There is no consistent pattern between the effect and the ability to express one or more of the FBPs . A single peptide may be insufficient to prevent GAS adherence to host cells.

Arch Oral Biol, 2004 Oct, 49(10), 783 - 8
Contribution of glucan-binding protein C of Streptococcus mutans to bacteremia occurrence; Nomura R et al.; Our previous analysis of major cell surface proteins of Streptococcus mutans isolated from the blood of a patient with bacteremia showed variations of glucan-binding protein C (GbpC) expression . In the present study, we analyzed the contribution of GbpC of S . mutans to bacteremia occurrence . A GbpC-defective mutant strain (C1) was significantly less susceptible to phagocytosis by human polymorphonuclear leukocytes than its parent strain (MT8148) (P < 0.001) . When 21 rats were injected with C1 or streptomycin-resistant MT8148R into the jugular vein, strain C1 was recovered from blood in larger numbers and for a longer duration than MT8148R . Further, infection with C1 resulted in significant increases in serum sialic acid (SSA) concentrations, and splenomegaly, as well as body weight reduction . We also evaluated GbpC expression in 20 clinical oral isolates by immunoblotting with anti-GbpC serum, and found that expression intensity was positively correlated to phagocytosis rate (P < 0.05) . These results suggest that S . mutans GbpC may be associated with systemic virulence, since a weak expression of GbpC causes the organisms to be refractory to phagocytosis, resulting in a longer survival of the bacterium in the bloodstream.

Vaccine, 2004 Sep 3, 22(25-26), 3334 - 9
Serotype distribution and antimicrobial resistance patterns of nasopharyngeal and invasive Streptococcus pneumoniae isolates in Hong Kong children; Ho PL et al.; A study was conducted to determine the vaccine coverage of prevalent carriage and invasive pneumococci from children aged less than 6 years in Hong Kong . A total of 383 nasopharyngeal carriage isolates and 88 invasive isolates from diverse sources were serotyped and their antimicrobial susceptibilities determined . The most common carriage serotypes were the same as the invasive isolates (6B, 14, 19F and 23F), although the rank order of specific serotypes was different . Serotypes in the 7-valent conjugate pneumococcal vaccine (4, 6B, 9V, 14, 18C, 19F and 23F) accounted for 89.7 and 66.1% of the invasive and carriage isolates, respectively . The same seven serotypes comprised 87.5% invasive isolates and 82.8% carriage isolates with resistance to penicillin, erythromycin and/or cefotaxime.

Scand J Infect Dis, 2004, 36(6-7), 485 - 8
Kinetics of immune parameters in a patient with sepsis caused by Streptococcus pyogenes treated with activated protein C; Holub M et al.; We report a case of streptococcal sepsis treated with recombinant human activated protein C (rhAPC) . High plasma IL-6 and cortisol levels at baseline significantly decreased 24 h following the infusion of rhAPC . This decrease was accompanied by a rise of circulating lymphocyte subsets . Our observation may be due to immunomodulatory properties of rhAPC.

Clin Infect Dis, 2004 Aug 1, 39(3), 380 - 8 Epub 2004 Jul 16.
Prevalence of group B streptococcus colonization and potential for transmission by casual contact in healthy young men and women; Manning SD et al.; Group B Streptococcus (GBS) causes disease in newborns, pregnant women, and adults with underlying medical conditions, but it is also a commensal organism that commonly colonizes the bowel . In this study, the prevalence of colonization was high among 241 women (34%) and 211 men (20%) living in a college dormitory; sexually experienced subjects had twice the colonization rates of sexually inexperienced participants . Other predictors of colonization varied by colonization site . Only 10 of the 142 roommate pairs had roommates who were both colonized with GBS, and 20% of these pairs shared identical strains, which is the same rate predicted by the population distribution . By contrast, a previous report found that 86% of co-colonized sex partners shared identical strains . GBS is likely transmitted by intimate contact, but transmission modes may vary by colonization site . Large prospective studies are needed to better understand colonization site-specific factors for GBS and to clarify potential transmission modes.

Mol Microbiol, 2004 Aug, 53(4), 1161 - 75
Defective cell wall synthesis in Streptococcus pneumoniae R6 depleted for the essential PcsB putative murein hydrolase or the VicR (YycF) response regulator; Ng WL et al.; PcsB is a protein of unknown function(s) that influences the cell morphology of several pathogenic species of streptococcus . PcsB contains a CHAP (cysteine, histidine-dependent amidohydrolase/peptidase) domain found in bacterial murein hydrolases; however, direct links between steps in cell wall biosynthesis and PcsB function(s) have not been demonstrated . We show here that pcsB is essential in the human respiratory pathogen, Streptococcus pneumoniae, that depletion of PcsB is bacteriostatic and that alanine substitutions in the conserved cysteine and histidine residues of the CHAP domain appear to be lethal . We stained wild-type parent and mutant bacteria deficient in expression of PcsB with fluorescent vancomycin and DAPI to determine patterns of cell wall synthesis and nucleoid segregation respectively . The wild-type parent strain exhibited ordered, simultaneous septal and equatorial cell wall synthesis . In contrast, reduced expression of PcsB resulted in formation of long chains of cells in which peptidoglycan synthesis occurred at nearly every division septum and cell equator . Severe depletion of PcsB led to abnormal, uncontrolled cell wall synthesis at misplaced septa and around large cells . Together, these physiological properties are consistent with a role for PcsB as a murein hydrolase that balances the extent of cell wall synthesis in S . pneumoniae . Finally, we show that the defects in morphology and cell wall synthesis that result from depletion of PcsB strongly resemble those caused by depletion of the essential VicRK two component regulatory system (TCS) . This result and the essentiality of pcsB support the hypothesis that the essentiality of the VicRK TCS results from its positive regulation of PcsB expression.

J Biol Chem, 2004 Oct 29, 279(44), 45909 - 18 Epub 2004 Aug 10.
Analysis of a novel prophage-encoded group A Streptococcus extracellular phospholipase A(2); Nagiec MJ et al.; Group A Streptococcus (GAS) is an important human pathogen that causes many types of infections, including pharyngitis and severe invasive diseases . We recently sequenced the genome of a serotype M3 strain and identified a prophage-encoded secreted phospholipase A(2) designated SlaA . To study SlaA structure-activity relationships, 20 site-specific mutants were constructed by alanine-replacement mutagenesis and purified to apparent homogeneity . Enzymatic activity was greatly reduced by alanine replacement of amino acid residues previously described as crucial in the catalytic mechanism of secreted phospholipase A(2) . Similarly, substitution of five residues in an inferred Ca(2+)-binding loop and three residues in the inferred active site region resulted in loss of activity of 76.5% or greater relative to the wild-type enzyme . Analysis of enzyme substrate specificity confirmed SlaA as a phospholipase A(2), with activity against multiple phospholipid head groups and acyl chains located at the sn-2 position . PCR analysis of 1,189 GAS strains representing 48 M protein serotypes commonly causing human infections identified the slaA gene in 129 strains of nine serotypes (M1, M2, M3, M4, M6, M22, M28, M75, and st3757) . Expression of SlaA by strains of these serotypes was confirmed by Western immunoblot . SlaA production increased rapidly and substantially on co-culture with Detroit 562 human pharyngeal epithelial cells . Together, these data provide new information about a novel extracellular enzyme that participates in GAS-human interactions.

JAMA, 2004 Aug 11, 292(6), 716 - 20
Association between carriage of Streptococcus pneumoniae and Staphylococcus aureus in Children; Regev-Yochay G et al.; CONTEXT: Widespread pneumococcal conjugate vaccination may bring about epidemiologic changes in upper respiratory tract flora of children . Of particular significance may be an interaction between Streptococcus pneumoniae and Staphylococcus aureus, in view of the recent emergence of community-acquired methicillin-resistant S aureus . OBJECTIVE: To examine the prevalence and risk factors of carriage of S pneumoniae and S aureus in the prevaccination era in young children . DESIGN, SETTING, AND PATIENTS: Cross-sectional surveillance study of nasopharyngeal carriage of S pneumoniae and nasal carriage of S aureus by 790 children aged 40 months or younger seen at primary care clinics in central Israel during February 2002 . MAIN OUTCOME MEASURES: Carriage rates of S pneumoniae (by serotype) and S aureus; risk factors associated with carriage of each pathogen . RESULTS: Among 790 children screened, 43% carried S pneumoniae and 10% carried S aureus . Staphylococcus aureus carriage among S pneumoniae carriers was 6.5% vs 12.9% in S pneumoniae noncarriers . Streptococcus pneumoniae carriage among S aureus carriers was 27.5% vs 44.8% in S aureus noncarriers . Only 2.8% carried both pathogens concomitantly vs 4.3% expected dual carriage (P =.03) . Risk factors for S pneumoniae carriage (attending day care, having young siblings, and age older than 3 months) were negatively associated with S aureus carriage . CONCLUSIONS: Streptococcus pneumoniae carriage, specifically of vaccine-type strains, is negatively associated with S aureus carriage in children . The implications of these findings in the pneumococcal vaccine era require further investigation.

JAMA, 2004 Aug 11, 292(6), 709 - 15
Safety and immunogenicity of a recombinant multivalent group a streptococcal vaccine in healthy adults: phase 1 trial; Kotloff KL et al.; CONTEXT: Group A streptococcal infections and their sequelae represent a global health problem . Recent advances have allowed previous obstacles associated with group A streptococcal vaccine development to be overcome . OBJECTIVE: To preliminarily evaluate the safety and immunogenicity of ascending doses of a recombinant fusion peptide group A streptococcal vaccine containing N-terminal M protein fragments from serotypes 1, 3, 5, 6, 19, and 24 in healthy volunteers . DESIGN, SETTING, AND PARTICIPANTS: An open-label, uncontrolled, dose-ascending phase 1 vaccine trial of 28 healthy adult volunteers aged 18 to 50 years recruited from the metropolitan area of Baltimore, Md, between October 5, 1999, and February 26, 2003, using newspaper advertisements and posted fliers, and evaluated in the outpatient facility of the Center for Vaccine Development . INTERVENTIONS: Each volunteer received 3 spaced intramuscular injections of 50 microg (n = 8), 100 micro g (n = 10), or 200 microg (n = 10) of hexavalent group A streptococcal vaccine formulated with aluminum hydroxide into the deltoid muscle of alternating arms . MAIN OUTCOME MEASURES: Assessments of clinical safety, including elicitation of antibodies that cross-react with host tissues, and immunogenicity as measured by enzyme-linked immunosorbent assay (ELISA) and assays of opsonophagocytic- and bactericidal-antibody responses . RESULTS: One year of intensive follow-up revealed the vaccine to be well tolerated . There was no evidence of tissue cross-reactive antibodies or immunological complications . At the highest (200 microg) dose, vaccination elicited significant increases in geometric mean antibody levels to all 6 component M antigens by ELISA (all P<.01) and to 5 of 6 M types in the opsonophagocytosis assay (all P<.05) . In addition, postvaccination increases in serum bactericidal activity of at least 30% were observed in 31 (55%) of 56 assays . CONCLUSION: These results provide the first evidence in humans that a hybrid fusion protein is a feasible strategy for evoking type-specific opsonic antibodies against multiple serotypes of group A streptococcus without eliciting antibodies that cross-react with host tissues, which represents a critical step in the development of a vaccine.

Trop Med Int Health, 2004 Aug, 9(8), 928 - 34
A prospective study of bloodstream infections as cause of fever in Malawi: clinical predictors and implications for management; Peters RP et al.; OBJECTIVE: To determine the contribution of a blood culture service to the diagnosis of fever in a resource-poor setting and to identify clinical predictors of specific bloodstream infections (BSI) . METHODS: In a descriptive, prospective study at the Medical Wards at Queen Elizabeth Central Hospital, Blantyre, Malawi, we tried to identify a specific cause of fever in febrile patients, comparing the use of routinely available diagnostic methods with the same methods plus blood culture . Clinical predictors of specific BSIs were sought . RESULTS: A total of 352 patients admitted with fever (axillary temperature > or =37.4 degrees C) or a history of fever within the last 4 days were enrolled . Tuberculosis (TB) was the diagnosis most commonly suspected initially on clinical grounds (28%), followed by lower respiratory tract infection (16%), malaria (12%) and gastroenteritis (5%) . Blood cultures were positive in 128 patients (36%); Mycobacterium tuberculosis was the most commonly isolated organism (57 patients) . In most cases the diagnosis of TB had already been made using routinely available diagnostic methods, including chest radiography . In all 16 cases of Streptococcus pneumoniae bacteraemia, infection with this agent was clinically suspected, usually on the basis of pulmonary symptoms and signs . In contrast, in 30 of 65 patients (65%) with non-typhi salmonellae (NTS) bacteraemia, there were no symptoms or signs specifically suggestive of this diagnosis . Fever > or =39 degrees C and splenomegaly predicted NTS bacteraemia with an odds ratio of 8.4 (95% confidence interval 3.4-20.6, P < 0.001) . CONCLUSION: BSIs are common among patients admitted with fever . While BSI with mycobacteraemia and S . pneumoniae can usually be predicted on clinical grounds and with routinely available diagnostic methods, NTS bacteraemia often presents as a primary BSI without localizing symptoms and signs . Splenomegaly in this population indicates NTS bacteraemia rather than malaria.

J Drugs Dermatol, 2004 Jul-Aug, 3(4), 409 - 13
Telithromycin: a brief review of a new ketolide antibiotic; Scheinfeld N; Telithromycin (Ketek, Aventis) is a semisynthetic antibacterial agent belonging to a class of drugs called ketolides, which are a variation on the existing class of antibiotics known as macrolides (e.g., erythromycin), whose structure includes a 14-molecule ring . The FDA approved telithromycin for use as a treatment for upper respiratory tract infections in April of 2004 . Its primary use is to treat community-acquired pneumonia and sinusitis . Telithromycin fulfills a role that has arisen due to the rise of microbial resistance to existing macrolides and appears to be effective against macrolide-resistant Streptococcus pneumoniae . The defining differentiating characteristic of the ketolides as opposed to other macrolides is the removal of the neutral sugar, L-cladinose from the 3 position of the macrolide ring and the subsequent oxidation of the 3-hydroxyl to a 3-keto functional group . Telithromycin seems to be an effective antibiotic in the treatment of a variety of skin infections, although double-blind trials have not proven this and currently no indication for treatment of skin infection is being sought from the FDA . Telithromycin also has excellent penetration into the female genial tract and could be useful for treating infections in this area.

Respir Med, 2004 Aug, 98(8), 708 - 20
Gemifloxacin once daily for 7 days compared to amoxicillin/clavulanic acid thrice daily for 10 days for the treatment of community-acquired pneumonia of suspected pneumococcal origin; Leophonte P et al.; CONTEXT: Community-acquired pneumonia (CAP) is common among adults and contributes considerably to morbidity and mortality . OBJECTIVE: To compare the safety and efficacy of gemifloxacin to high-dose amoxicillin/clavulanate for the treatment of CAP of suspected pneumococcal origin . DESIGN: Randomized, multicentre, double-blind, double-dummy, parallel group Phase III study . SETTING AND PARTICIPANTS: From September 1998 to July 1999, 324 patients with CAP were randomized at 102 centers in France, Poland and the Republic of South Africa . INTERVENTION: Patients were double-blind randomized to receive either oral gemifloxacin 320 mg once daily for 7 days or oral amoxicillin/clavulanate 1 g/125 mg three times daily for 10 days . MAIN OUTCOME MEASURES: The main outcome measures were clinical, bacteriological, and radiological responses at the end of therapy (day 12-14) and follow-up (day 24-30) visits . RESULTS: In 228 PP patients, clinical resolution at follow-up was 88.7% for 7-day gemifloxacin and 87.6% for 10-day amoxicillin/clavulanate {95% CI, -7.3, 9.5} . In 249 PP patients, clinical resolution at end of therapy was 95.3% for 7-day gemifloxacin vs . 90.1% for 10-day amoxicillin/clavulanate {95% CI, -1.2, 11.7} . Bacteriologic response rates for the PP patients at end of therapy were 96.3% for 7-day gemifloxacin and 91.8% for the amoxicillin/clavulanate group {95% CI, -4.7, 13.6} . Bacteriologic response rates at follow-up were 87.2% for 7-day gemifloxacin and 89.1% for the amoxicillin/clavulanate group {95% CI, -15.0, 11.2} . Specifically gemifloxacin eradicated 95.7% of Streptococcus pneumoniae including penicillin and macrolide resistant strains . Radiological response rates for the PP patients at end of therapy were 89.1% for 7-day gemifloxacin and 87.6% for the amoxicillin/clavulanate group . The most frequently reported drug-related events were in the gemifloxacin group, diarrhea (6.0%) and rash (3.0%) and in the amoxicillin/clavulanate group, diarrhea (11.1%) and fungal infection, vaginitis and vomiting (each 2.0%) . Overall there were statistically fewer withdrawals due to lack of therapeutic effect in the gemifloxacin group compared with the amoxicillin/clavulanate cohort, (95% CI, -8.8;0.6; P = 0.03) . CONCLUSION: Gemifloxacin 320 mg once daily for 7 days was found to be clinically, bacteriologically, and radiologically as effective as 10 days of amoxicillin/clavulanate 1 g/125 mg three times daily for the treatment of suspected pneumococcal CAP.

Int J Pediatr Otorhinolaryngol, 2004 Sep, 68(9), 1209 - 13
Streptococcal necrotizing fasciitis with toxic shock syndrome following cervical adenitis; Sakran W et al.; In the recent years an increase of serious invasive infections due to Group A Streptococcus have been reported . Necrotizing fasciitis is a rapidly progressive soft tissue infection characterized by necrosis of the subcutaneous tissues and superficial fascia . We report a case of necrotizing fasciitis and toxic shock syndrome following cervical adenitis in a previously healthy 11-month-old boy . Cultures from blood and the necrotic lymph node grew Group A Streptococcus . Group A Streptococcus belonging to M1 serotype and producing streptococcal pyrogenic exotoxin, SPE A was identified . Full recovery was achieved by aggressive treatment, which included intensive care support, extensive surgical debridement of necrotic lesions and antibiotic treatment with the combination of penicillin and clindamycin.

Zhongguo Wei Zhong Bing Ji Jiu Yi Xue, 2004 Aug, 16(8), 454 - 7
{Analysis of etiological factors of pseudo-epitheliomatous granuloma after cutaneous wound healing: a report of 11 cases of patients with this lesion}; Jiang DY et al.; OBJECTIVE: To explore the pathogenetic mechanism, clinical and pathological characteristics, and prevention and treatment of pseudo-epitheliomatous granuloma after skin wound healing . METHODS: The clinical information and the treatment results of pseudo-epitheliomatous granuloma occurring in 11 patients (age 1-67 years) were reviewed and analyzed, their tissue specimens were used for microbial examination and histological observation . RESULTS: Some bacteria such as Staphylococcus aureus, Pseudomonas pyocynea, Streptococcus hemolyticus B, and Streptococcus feacalis could be found in the culture of pseudo-epitheliomatous granuloma . The maJority of these bacteria was tolerant to celbenin but sensitive to vancomycin . The lesions were excised, and the wounds were covered with skin grafting or skin flap, supplemented by local of vancomycin to prevent recurrence of the lesion . Histological examination revealed in pseudo-epitheliomatous granuloma with long epithelial peduncle encapsulating granulation tissue like honeycomb, in which there were many capillaries, macrophages, lymphocytes and mast cells, with only a small amount of extracellular matrix . CONCLUSION: The main pathogenesis of pseudo-epitheliomatous granuloma formation might be improper treatment of wound in earlier period and infection of drug resistant bacteria . Surgical debridement followed by skin coverage and local inJection of vancomycin could be effective and curative.

Berl Munch Tierarztl Wochenschr, 2004 Jul-Aug, 117(7-8), 266 - 70
Response of Streptococcus suis to iron-restricted growth conditions at high and low oxygen availability; Winterhoff N et al.; Streptococcus suis (S . suis) is an important pathogen in pigs and has to overcome strict iron limitations in its host environment . Here, we studied iron-restricted growth of a highly virulent S . suis strain in vitro at aerobic and CO2-enriched growth conditions . At both conditions, depleting of iron in the culture medium with nitrilotriacetic acid (NTA) resulted in decreased growth rates and down regulation of several proteins . Sensitivity to NTA was significantly higher at aerobic versus CO2-enriched conditions . Growth could not be restored by addition of host iron sources such as ferritin, hemin, hemoglobin, lactoferrin or transferrin . Accordingly, S . suis was not able to produce detectable amounts of siderophores . On the other hand, growth at iron-restricted conditions was fully restored by addition of Mn2+ (at aerobic and CO2-enriched conditions) or Mg2+ (only at CO2-enriched conditions) . In conclusion our results suggest that, unlike many other bacteria, S . suis adapts to iron restricted conditions by a change in its metabolism in order to replace Fe2+ by Mn2+ or Mg2+ rather than by expressing specific iron uptake systems.

Curr Microbiol, 2004 Jul, 49(1), 59 - 65
Isolation and some properties of fimbriae of oral Streptococcus intermedius; Yamaguchi T et al.; Streptococcus intermedius 1208-1 carried linear fiber-like fimbriae that extended radially from the cell surface . The fimbriae were isolated by pipetting and sonication and were purified by ammonium sulfate precipitation followed by a column chromatography series . Heat treatment in the presence of sodium dodecyl sulfate resulted in the dissociation into smaller molecules . Rabbit antiserum raised against the purified protein reacted with fimbriae on the surface of bacteria under immunogold staining . Serotype g or g-related strains produced the fimbriae and aggregated in human saliva . The aggregation was inhibited by the anti-fimbriae immunoglobulin Fab fragment or the purified fimbriae.

Curr Microbiol, 2004 Jul, 49(1), 4 - 9
Molecular characteristics of phosphoenolpyruvate: mannose phosphotransferase system in Streptococcus bovis; Asanuma N et al.; To elucidate the regulatory mechanism of catabolite control in Streptococcus bovis, we investigated the molecular properties and gene expression of the mannose-specific phosphoenolpyruvate (PEP)-dependent sugar: phosphotransferase system (PTS) . The mannose PTS gene cluster (man) was found to comprise a gene encoding enzyme (E) II AB (manL) and genes encoding EIIC (manM), EIID (manN), and a putative regulator (manO) . The gene cluster (man operon) was transcribed from one transcriptional start site, which was located 40 bp upstream of the manL start codon . However, two transcriptional start sites were found between manN and manO in primer extension analysis, and the manO may be transcribed independently from the man operon . The man operon and manO were constitutively transcribed without being affected by culture conditions, such as the sugar supplied (glucose, galactose, fructose, maltose, lactose, sucrose, or mannose), growth rate, or pH.

Curr Microbiol, 2004 Aug, 49(2), 115 - 22
Influence of dipeptidyl peptidase inhibitors on growth, peptidase activity, and ammonia production by ruminal microorganisms; Wang H et al.; The aim was to investigate known and potential new inhibitiors of dipeptidyl peptidases (DPP) for their effects on ruminal microorganisms . Gly-Phe diazomethylketone (GPD), Ala-Ala chloromethylketone (AAC), benserazide (DL-serine 2-(2,3,4- trihydroxybenzyl) hydrazide), and diprotin A (Ile-Pro-Ile) inhibited DPP activities of Prevotella albensis, P . ruminicola, P . bryantii, P . brevis, and mixed ruminal microorganisms, though incompletely and, except for diprotin A, without absolute specificity for any of the peptidases . Leucine aminopeptidase activity of Streptococcus bovis was also inhibited by GPD and benserazide . The inhibitors had no effect on the growth of the bacteria, except for GPD, which inhibited growth of P . albensis when only peptides were available for growth . Benserazide had some inhibitory effects on the growth of Megasphaera elsdenii and Prevotella spp., even in the absence of peptides . The predatory activity of ciliate protozoa on bacteria was unaffected by DPP inhibitors . Ammonia production from casein by mixed ruminal microorganisms was inhibited significantly (P < 0.05) by AAC (29% inhibition) and benserazide (33%) . It was concluded that DPP inhibitors can influence the rate of NH3 production in the rumen and may form the basis for developing protein-sparing feed additives for ruminants.

J Clin Microbiol, 2004 Aug, 42(8), 3844 - 6
Clonal spread of emm type 28 isolates of Streptococcus pyogenes that are multiresistant to antibiotics; Mihaila-Amrouche L et al.; Fifty-three pharyngitis-related and invasive isolates of Streptococcus pyogenes that are resistant to bacitracin were collected . They were also resistant to streptomycin, kanamycin, macrolides, lincosamides, and streptogramin B . These multiresistant isolates were of emm type 28 and clonally related as shown by pulsed-field gel electrophoresis.

J Clin Microbiol, 2004 Aug, 42(8), 3570 - 4
Characterization and prevalence of MefA, MefE, and the associated msr(D) gene in Streptococcus pneumoniae clinical isolates; Daly MM et al.; Recent work has shown that the efflux genes in Streptococcus pneumoniae that are responsible for acquired macrolide resistance can be distinguished as either mef(E) or mef(A) . The genetic elements on which mef(A) and mef(E) are found also carry an open reading frame (ORF) that is 56% homologous to msr(A) in Staphylococcus . The prevalence of mef(A/E) and of the msr-like ORF {msr(D)} was evaluated in 153 mef(+) S . pneumoniae clinical isolates collected in North America, Europe, Africa, and Asia from 1997 to 2002 . Clinical isolates were screened with PCR primers specific for either mef(A) or mef(E) and for msr(D) . mef(A), mef(E), and msr(D) were cloned from mef(+) strains and transformed into a susceptible, competent strain of S . pneumoniae . The transformants were tested for antimicrobial susceptibilities and efflux pump induction . The results of this work demonstrated that mef(A) is more often isolated in parts of Europe, with some incidence in Canada, and that the msr-like gene alone can confer the efflux phenotype.

J Infect Dis, 2004 Sep 1, 190(5), 928 - 34 Epub 2004 Jul 28.
Level of maternal IgG anti-group B streptococcus type III antibody correlated with protection of neonates against early-onset disease caused by this pathogen; Lin FY et al.; The present study estimates the level of maternal immunoglobulin (Ig) G anti-group B streptococcus (GBS) type III required to protect neonates against early-onset disease (EOD) caused by this pathogen . Levels of maternal serum IgG anti-GBS type III, measured by enzyme-linked immunosorbent assay, in 26 case patients (neonates with EOD caused by GBS type III) and 143 matched control subjects (neonates colonized by GBS type III who did not develop EOD) of > or = 34 weeks gestation were compared . The probability of EOD decreased with increasing levels of maternal IgG anti-GBS type III (P = .01) . Neonates whose mothers had > or = 10 microg/mL IgG anti-GBS type III had a 91% lower risk for EOD, compared with those whose mothers had levels of < 2 microg/mL . A vaccine that induces IgG anti-GBS type III levels of > or = 10 microg/mL in mothers can be predicted to offer a significant degree of protection against EOD caused by this pathogen.

Pediatr Infect Dis J, 2004 Aug, 23(8), 779 - 81
Epidemiology of invasive Streptococcus pneumoniae infections and vaccine implications among children in a West Virginia community, 1978-2003; Mufson MA et al.; From 1978 to 2003, in Huntington, WV, we investigated Streptococcus pneumoniae invasive disease and the effect of conjugated pneumococcal vaccine among 161 children 14 years of age and younger admitted to the hospital . During 2002 and 2003, the number and proportion of invasive disease caused by vaccine strains declined; and in 2003, no invasive disease occurred in young children, suggesting a vaccine effect.

Appl Environ Microbiol, 2004 Aug, 70(8), 5037 - 40
Direct production of ethanol from raw corn starch via fermentation by use of a novel surface-engineered yeast strain codisplaying glucoamylase and alpha-amylase; Shigechi H et al.; Direct and efficient production of ethanol by fermentation from raw corn starch was achieved by using the yeast Saccharomyces cerevisiae codisplaying Rhizopus oryzae glucoamylase and Streptococcus bovis alpha-amylase by using the C-terminal-half region of alpha-agglutinin and the flocculation functional domain of Flo1p as the respective anchor proteins . In 72-h fermentation, this strain produced 61.8 g of ethanol/liter, with 86.5% of theoretical yield from raw corn starch.

Appl Environ Microbiol, 2004 Aug, 70(8), 4569 - 74
Expression and immunogenicity of a recombinant diphtheria toxin fragment A in Streptococcus gordonii; Lee CW et al.; A nontoxic mutant diphtheria toxin fragment A (DTA) was genetically fused in single, double, or triple copy to the major surface protein antigen P1 (SpaP) and surface expressed in Streptococcus gordonii DL-1 . The expression was verified by Western immunoblotting . Mouse antisera raised against the recombinant S . gordonii recognized the native diphtheria toxinm suggesting the recombinant DTA was immunogenic . When given intranasally to mice with cholera toxin subunit B as the adjuvant, the recombinant S . gordonii expressing double copies of DTA (SpaP-DTA(2)) induced a mucosal immunoglobulin A response and a weak systemic immunoglobulin G response . S . gordonii SpaP-DTA(2) was able to orally colonize BALB/c mice for a 15-week period and elicited a mucosal response, but a serum immunoglobulin G response was not apparent . The antisera failed to neutralize diphtheria toxin cytotoxicity in a Vero cell assay.

Mikrobiyol Bul, 2004 Jan-Apr, 38(1-2), 1 - 7
{The epidemiology of nasopharyngeal colonisation of Streptococcus pneumoniae in children with respiratory tract infection}; Ilki A et al.; Nasopharyngeal swab specimens from 324 children with respiratory tract infections were evaluated to detect the rate of Streptococcus pneumoniae colonisation . S . pneumoniae was detected in 92 (28%) of the subjects . Forty three (46.7%) of the isolates were serotyped by the capsular swelling tests . The most common serotypes were 19F, 6B, 3 and 23F . The 7, 9 and 11 valent conjugate pneumococcal vaccines covered 35.8%, 40% and 46.7% of all the S . pneumoniae isolates, respectively . Thirty two (34.8%) isolates exhibited penicillin MIC values between 0.1 and 1 microg/ml, only 1 isolate had MIC > or = 2 microg/ml . Penicillin resistant pneumococcal colonisation was most frequently detected in children with viral upper respiratory tract infections (12.5%) . Resistance rates of trimetoprim-sulfamethoxazole, erythromycin, chloramphenicol, clindamycin, ceftriaxone, rifampin were 31.5%, 9.8%, 6.5%, 4.3%, 1%, 0%, respectively . Being a children of a family with low income was the only risk factor for colonisation with S . pneumoniae, whereas having a sibling attending to a day care center, antibiotic use in the last three months and use of more than one antibiotic were significant risk factors for colonisation with penicillin resistant S . pneumoniae (p < 0.05).

Eur Respir J, 2004 Jul, 24(1), 143 - 9
Immunokinetics in severe pneumonia due to influenza virus and bacteria coinfection in mice; Seki M et al.; Coinfections of bacteria and influenza are a major cause of excessive mortality during influenza epidemics . However, the mechanism of the synergy between influenza virus and bacteria are poorly understood . In this study, mice were inoculated with influenza virus, followed 2 days later by inoculation with Streptococcus pneumoniae . The kinetics of viral titres, bacterial numbers and the immune response (cytokine and chemokine production) were also analysed . Short-term survival correlated with pathological changes in the lungs of infected mice . Influenza virus or S . pneumoniae infection alone induced moderate pneumonia; however, severe bronchopneumonia with massive haemorrhage in coinfected mice, which caused death of these mice approximately 2 days after inoculation with S . pneumoniae, was noted . Intrapulmonary levels of inflammatory cytokines/chemokines, type-1 T-helper cell cytokines and Toll-like receptors, and the related mitogen-activated protein kinase signalling molecules (phosphorylated extracellular signal-regulated kinase -1 and - 2, p38 and c-Jun N-terminal kinase), were increased in coinfected mice . These results suggest that immune mediators, including cytokines and chemokines, through Toll-like receptors/mitogen-activated protein kinase pathways, play important roles in the pathology of coinfection caused by influenza virus and Streptococcus pneumoniae.

J Nephrol, 2004 Mar-Apr, 17(2), 236 - 41
Bacterial meningitis in hemodialyzed patients; Cheng BC et al.; BACKGROUND: To analyze the clinical features, causative pathogens and therapeutic outcomes of bacterial meningitis in hemodialyzed patients . PATIENTS AND METHODS: Two hundred and sixty-seven patients, > or = 16 yrs, were identified with culture-proven bacterial meningitis . In addition, the causative pathogens and therapeutic outcomes between uremic and non-uremic patients with adult bacterial meningitis were analyzed . RESULTS: Nine uremic patients with bacterial meningitis, accounting for 3% (9/267) of our adult patients with culture-proven bacterial meningitis had fever, disturbed consciousness and seizures . These were the three most common manifestations in our patients . The interval between the onset of symptoms and therapy start was 5-11 days (mean: 9 days) . No patients were initially diagnosed with bacterial meningitis, two patients were initially suspected of having infection of unknown origin . In the non-uremic patient group, klebsiella pneumoniae, Staphylococcus aureus, and Streptococcus pneumoniae were the most frequently detected pathogens, while pseudomonas aeruginosa and coagulase-negative Staphylococcus were the most prevalent in the uremic patients group . The overall mortality rates for the non-uremic and uremic patient groups were 33 and 78% respectively . CONCLUSION: The mortality rate for bacterial meningitis in the uremic patients group remained high . Due to non-specific manifestations and slow evolution, bacterial meningitis was commonly misdiagnosed as uremic encephalopathy . Therefore, effective treatment was usually delayed . To avoid treatment failure, early diagnosis, careful monitoring of clinical condition and appropriate antibiotic choices are necessary.

Am J Infect Control, 2004 Aug, 32(5), 287 - 90
Toys in a pediatric hospital: are they a bacterial source?
Avila-Aguero ML, German G, Paris MM, Herrera JF; Safe Toys Study Group.
BACKGROUND: In children's hospitals, children are commonly provided with toys . Measures to guarantee the safety of these toys are usually not taken . This study was conducted to determine whether toys were contaminated with potentially pathogenic bacteria when they arrived in the hospital, and whether they were contaminated in the hospital . METHODS: The study was conducted during a 3-month period . Children who were hospitalized for at least 3 days were chosen as study subjects . Once these children were identified, cultures from their toys were obtained within the first 48 hours of admission . After this first culture, toys were cleaned with 4% chlorhexidine and water and were immediately re-cultured . Following cultures were collected on days 5 to 7, 10 to 15, and every week thereafter until the owner-patient was discharged . Specimens were collected in a standardized manner with moistened swabs and placed in transport media . They were later inoculated onto trypticase soy agar with 5% sheep blood and brain heart infusion agar, incubated at 37 degrees C for 48 hours and examined for colony growth at 24 to 48 hours . RESULTS: Seventy children's toys were included in this study . Patients' median age was 26 months (range: 1 day to 9 years) . Respiratory infections (43%) and diarrhea (26%) were the most common causes of hospitalization . Fifty-three (76%) toys were made of plastic, 8 (11%) metallic, and 9 (13%) other materials . Twenty-nine (41%) were brought from home, 38 (55%) were purchased from roving vendors, and 3 (4%) were purchased from toy stores . All first cultures were positive for at least 1 pathogenic microorganism: 55 (78%) coagulase-negative Staphylococcus (CNS); 26 (37%) Bacillus spp; 13 (18%) Staphylococcus aureus; 8 (11%) alpha-hemolytic Streptococcus; 5 (9%), Pseudomonas spp; 2 (3%) Stenotrophomonas maltophilia, and 6 (11%) other gram-negative organisms . After toys were cleaned, subsequent cultures showed significant decreases in bacterial growth rates (P <.05) . Because some patients were discharged, additional cultures were obtained for only 31 toys . CONCLUSIONS: Toys entering a hospital can be contaminated with potentially dangerous bacteria and may provide unnecessary risks for nosocomial infection . Effective measures must be implemented to prevent the spread of infections via toys.

Pediatr Neurosurg, 2004 Mar-Apr, 40(2), 64 - 9
In vitro bacterial adherence to ventriculoperitoneal shunts; Livni G et al.; Bacterial adherence to medical devices has been recognized as an important initial step in the infectious process, but it has not been fully elucidated regarding ventriculoperitoneal (VP) shunts . The aim of the present study was to quantitatively determine the adherence in vitro of bacteria known to cause VP shunt infections and to identify factors affecting the process . Clinical isolates studied included Staphylococcus epidermidis, Staphylococcus aureus, Streptococcus pneumoniae, and Escherichia coli . Adherence was examined quantitatively per square centimeter, visualized by electron microscopy and related to slime production and hydrophobicity . Although all four strains adhered to VP shunts, there were marked differences, with S . epidermidis and S . aureus showing the highest adherence (67.0 x 10(3) and 15.2 x 10(3) bacteria/cm(2), respectively) . Factors affecting adherence included incubation time and temperature, bacterial concentration, device material (lower for silicone than Teflon), slime production and hydrophobicity . These data might be helpful for devising novel strategies to reduce VP shunt infections.

J Bacteriol, 2004 Aug, 186(16), 5258 - 66
Control of virulence by the two-component system CiaR/H is mediated via HtrA, a major virulence factor of Streptococcus pneumoniae; Ibrahim YM et al.; The CiaR/H two-component system is involved in regulating virulence and competence in Streptococcus pneumoniae . The system is known to regulate many genes, including that for high-temperature requirement A (HtrA) . This gene has been implicated in the ability of the pneumococcus to colonize the nasopharynx of infant rats . We reported previously that deletion of the gene for HtrA made the pneumococcal strains much less virulent in mouse models, less able to grow at higher temperatures, and more sensitive to oxidative stress . In this report, we show that the growth phenotype as well as sensitivity to oxidative stress of Delta ciaR mutant was very similar to that of a Delta htrA mutant and that the expression of the HtrA protein was reduced in a ciaR-null mutant . Both the in vitro phenotype and the reduced virulence of Delta ciaR mutant could be restored by increasing the expression of HtrA.

Lakartidningen, 2004 Jul 8, 101(28-29), 2336 - 41
{13 cases of cervical necrotizing fasciitis--all patients survived . Surgery, antibiotics and hyperbaric oxygenation give the best results}; Stenberg AE et al.; Cervical necrotizing fasciitis is a serious, rapidly progressive infection along fascia planes that sometimes involves skin, subcutaneous tissue and muscle (myositis) . The condition, often of dental or pharyngeal origin, is associated with high morbidity and mortality . Thirteen consecutive cases of cervical necrotizing fasciitis treated with hyperbaric oxygen at the Karolinska Hospital during the period 1997-2003 were reviewed . Eight male and five female patients, 33 to 78 years old, were treated according to the Karolinska Hospital guidelines for severe soft tissue infections . All patients recovered . Eleven of thirteen patients required intensive care and eight inotropic drugs . Streptococcus milleri was the predominant pathogen found in initial cultures . Three case reports are presented . Our findings lend further support to the literature on the importance of a prompt multidisciplinary approach with aggressive surgical intervention, broad-spectrum antibiotic therapy and hyperbaric oxygen therapy.

Sichuan Da Xue Xue Bao Yi Xue Ban, 2004 Jul, 35(4), 555 - 8
{Purification and characterization of sanguicin--a bacteriocin produced by Streptococcus sanguis}; Deng H et al.; OBJECTIVE: Streptococcus sanguis plays an important Role in maintaining the periodontal microecological balance . Previous studies have demonstrated that sanguicin--a kind of bacteriocin produced by S . sanguis has a prominent function of inhibiting the growth of putative periodontopathic bacteria (PPB) . The aim of this study was to purify sanguicin and investigate its characters . METHODS: The raw extract of sanguicin was obtained from cells of S . sanguis by ultrasonication, salting out and dialysis . Then the diethyl-aminoethyl-sepharose gradual washing was done in conjunction with glucosan gel filtration for in the purfication of sanguicin . The characters of purified sanguicin were determined and its inhibitiory effect on PPB was measured by agar diffusion test . RESULTS: The purifed sanguicin was obtained; it was heat labile and proteinaceous; and by SDS-PAGE, it showed a main band with the relative molecular mass of 65 x 10(3) . The purifed sanguicin had a strong inhibitory effect on P . gingivalis, P . intermedia and F . nucleatum in vitro . CONCLUSION: Our methods are useful for the purification of sanguicin . Sanguicin has inhibitory effect on PPB obviously and will have a good prospect in periodontal ecological therapy.

Sichuan Da Xue Xue Bao Yi Xue Ban, 2004 Jul, 35(4), 520 - 1
{Evaluation of the in vitro cariogenic potential of Streptococcus mutans (serotype C) strains isolated from caries-free and -active people: the ability of acidogenicity}; Huang XJ et al.; OBJECTIVE: To investigate the ability of acidogenicity of S . mutans (serotype C) strains isolated from the people with different caries experience . METHODS: Same density solutions of all isolated S . mutans were made and cultured in different pH TPPE liquid for the same period of time . Terminal pH of the solutions was measured . The values of delta pH were compared . RESULTS: Significant difference of acidogenicity was observed between the strains of different genotypes isolated from the same person . The ratio of high acidogenicity isolates harbored in caries-active people was greater than that of caries-free people; a significant difference was noted (P<0.05) . CONCLUSION: The high cariogenicity of isolated S . mutans strains of caries-active people shows a close relationship with the high acidogenicity of the isolated S . mutans (serotype C) strains.

J Dairy Sci, 2004 May, 87(5), 1256 - 64
Somatic cell count distributions during lactation predict clinical mastitis; Green MJ et al.; This research investigated somatic cell count (SCC) records during lactation, with the purpose of identifying distribution characteristics (mean and measures of variation) that were most closely associated with clinical mastitis . Three separate data sets were used, one containing quarter SCC (n = 1444) and two containing cow SCC (n = 933 and 11,825) . Clinical mastitis was defined as a binary outcome, present or absent, for each lactation, and SCC were log (base 10) transformed . A generalized linear mixed model within a Bayesian framework was used for analysis . Parameters were estimated using Markov Chain Monte Carlo with Gibbs sampling . Results from the 3 data sets were similar . Increased maximum and standard deviation log SCC during lactation, rather than increased geometric mean, were the best overall indicators of clinical mastitis . Distributions of SCC were also investigated separately for different mastitis pathogens . Increased maximum log SCC was associated with clinical mastitis caused by all pathogen types . Increased standard deviation log SCC was associated with Staphylococcus aureus, and Streptococcus uberis clinical mastitis and increased coefficient of variation log SCC (standard deviation divided by mean) was associated with Escherichia coli clinical mastitis . Increased geometric mean lactation SCC was associated with an increased risk of Staph . aureus clinical mastitis but a reduced risk of E . coli clinical mastitis . Our results suggest that using measures of variation and maximum cow SCC would enhance the accuracy of predicting clinical mastitis, compared with geometric mean SCC, and therefore improve genetic programs that aim to select for clinical mastitis resistance . The results are also consistent with low SCC increasing susceptibility to some mastitis pathogens.

Cancer Res, 2004 Aug 1, 64(15), 5461 - 70
Expression of toll-like receptor 4 on dendritic cells is significant for anticancer effect of dendritic cell-based immunotherapy in combination with an active component of OK-432, a streptococcal preparation; Okamoto M et al.; A lipoteichoic acid-related molecule OK-PSA is an active component of OK-432, a Streptococcus-derived anticancer immunotherapeutic agent . In the present study, we first examined the effect of OK-PSA on the maturation of dendritic cells (DCs) in vitro by using the DCs derived from 5 healthy donors and 10 patients with head and neck cancer with or without expression of toll-like receptor 4 (TLR4) or MD-2 mRNA . OK-PSA treatment effectively increased the surface expression of MHC class II, CD80, CD83, and CD86 . OK-PSA-stimulated DCs secreted the cytokines that can induce helper T-cell 1 (Th1)-type T-cell response, and stimulated allogeneic T cells to produce IFN-gamma and to elicit an allogeneic antigen-specific cytotoxicity . These activities almost depended on expression of TLR4 and MD-2 genes . We next investigated the in vivo anticancer effect of intratumoral administration of syngeneic DCs followed by OK-PSA against established tumors in mice . C57BL/6 mice, which express wild-type TLR4, and C57BL/6-derived TLR4-knockout (TLR4(-/-)) mice were used . Although OK-PSA accelerated the antitumor effect of intratumoral DC administration in wild-type mice bearing syngeneic tumors, the antitumor effect of OK-PSA as well as of the combination therapy with DCs and OK-PSA was not significant in TLR4(-/-) mice . Interestingly, an administration of wild-type-mouse-derived DCs followed by OK-PSA exhibited a marked antitumor effect even in the TLR4(-/-) mice . These findings suggest that OK-PSA may be a potent adjuvant for local DC therapy, and that DC therapy followed by OK-PSA is able to elicit anticancer activity even in a TLR4-deficient host when TLR4 is expressed only in DCs injected intratumorally.

Am J Ophthalmol, 2004 Aug, 138(2), 231 - 6
Endophthalmitis caused by Streptococcus pneumoniae; Miller JJ et al.; PURPOSE: To investigate clinical settings, management strategies, antibiotic sensitivities, and visual acuity outcomes of endophthalmitis caused by Streptococcus pneumoniae . DESIGN: Retrospective, observational case series . METHODS: Records were reviewed of all patients with culture-positive endophthalmitis caused by Streptococcus pneumoniae treated at the Bascom Palmer Eye Institute between January 1, 1989 and December 31, 2003 . MAIN OUTCOME MEASURES: Visual acuity and antibiotic sensitivities . RESULTS: Twenty-seven eyes of 27 patients met study inclusion criteria . The median follow-up was 7 months (range, 3 months to 10 years) . Clinical settings included acute postoperative (10 eyes), corneal stitch abscess (5), corneal ulcer (3), bleb-associated (4), post-trauma (3), and endogenous (2) . Eighteen cases (67%) were acute-onset (less than 3 weeks from event), with a median interval between event and presentation of endophthalmitis of 5 days (range, 1 day to 16 days) . Nine cases (33%) were delayed-onset (median, 27 months; range, 3 to 121 months) . Initial visual acuity was hand motions or better in 11 cases (41%) . Initial therapeutic procedures included vitreous tap and injection of intravitreal antibiotics in 15 eyes (56%), pars plana vitrectomy and injection of intravitreal antibiotics in 10 eyes (37%), and evisceration in 2 eyes (7%) . Seventeen (68%) of 25 eyes received intravitreal dexamethasone . Twelve patients (48%) received additional doses of intraocular antibiotics, and 11 patients (44%) underwent secondary surgical intervention within one week of diagnosis . The Streptococcus pneumoniae isolates showed sensitivity patterns as follows: 27/27 vancomycin, 13/13 clindamycin, 6/6 cefazolin, 11/11 ciprofloxacin, 14/14 moxifloxacin, 24/26 (92%) ofloxacin, 12/14 (86%) levofloxacin, 13/14 (93%) gatifloxacin, and 1/13 (8%) gentamicin . The organism was sensitive to at least one antibiotic administered initially in all cases . Final visual acuity was 20/400 or better in 8/27 (30%) cases, but 10 eyes (37%) had a final vision of no light perception . CONCLUSION: Despite prompt treatment with appropriate antibiotics, endophthalmitis caused by Streptococcus pneumoniae is associated with a poor visual prognosis.

Int J Antimicrob Agents, 2004 Aug, 24(2), 185 - 7
In vitro activity of older and newer fluoroquinolones against efflux-mediated high-level ciprofloxacin-resistant Streptococcus pneumoniae; Daporta MT et al.; The effect of high-level efflux activity on the MICs of fluoroquinolones against Streptococcus pneumoniae in the absence of topoisomerase mutations leading to fluoroquinolones resistance was investigated . A S . pneumoniae ATCC 46619-derived strain with high-level efflux activity was obtained (SP-25A) . Both the parent and obtained strains were tested against efflux substrates acriflavine (Acr) and ethidium bromide (EtBr), and against norfloxacin (NFX), ciprofloxacin (CFX), levofloxacin (LFX), moxifloxacin (MFX), trovafloxacin (TVX) and sitafloxacin (SFX), in presence and absence of the efflux pump inhibitor reserpine . gyrA, gyrB, parC and parE QRDR genes were amplified by PCR and sequenced . MICs of NFX and CFX against SP-25A were 64-fold higher than parent strain MICs (256 mg/L versus 4 mg/L and 64 mg/L versus 1mg/L, respectively) . MIC of LFX increased from 1 to 4 mg/L and MICs of MFX, TVX and SFX remained virtually unchanged (0.1-0.2 mg/L) . MICs of Acr and EtBr against SP-25A were 8- and 16-fold higher than against parent strains . In both cases, reserpine reverted MICs to the parent strain values (1 and 0.2 mg/L) . Only parE showed two mutations leading to a Pro(454) --> Ser and Glu(443) changes, which have previously been shown not to lead to significant fluoroquinolones MIC increases . SP-25A showed a significant increase of MICs of the hydrophilic fluoroquinolones, apparently derived only from efflux activity . Efflux activity, at these high levels, can lead to high-level resistance to older hydrophilic fluoroquinolones, but does affect newer fluoroquinolones such as moxifloxacin, trovafloxacin and sitafloxacin.

Int J Antimicrob Agents, 2004 Aug, 24(2), 178 - 80
In vitro antagonism between beta-lactam and macrolide in Streptococcus pneumoniae: how important is the antibiotic order?
Ortega M, Marco F, Soriano A, Gomez J, Almela M, Mensa J.
We found that the in vitro interaction between penicillin or cefotaxime and erythromycin against Streptococcus pneumoniae varies depending on the order of antibiotic exposure . Time-kill experiments were performed with penicillin, cefotaxime, erythromycin and different order combinations of both beta-lactams with erythromycin . The mean difference between the colony count at 0 and 6h for penicillin, cefotaxime and erythromycin tested separately was 3.5 log cfu/mL, 2.4 and 1.5 respectively for susceptible strains . The mean difference for the combination of beta-lactam and erythromycin studied simultaneously was 1.8 log cfu/mL for these strains . The association of penicillin or cefotaxime with erythromycin added two hours later showed an activity similar to those of beta-lactam alone (mean difference was 3.0 for this association with penicillin and 2.5 with cefotaxime) . Therefore, the antagonistic effect of macrolide activity could be less important if erythromycin was administrated after beta-lactam.

Int J Antimicrob Agents, 2004 Aug, 24(2), 144 - 9
Streptococcus pneumoniae in vitro development of resistance to amoxicillin/clavulanic acid, cefaclor, levofloxacin and azithromycin; Koeth LM et al.; The purpose of this study was to determine effect of repeated exposure to sub-inhibitory concentrations of amoxicillin/clavulanic acid on the development of resistance in Streptococcus pneumoniae . Other agents, azithromycin, cefaclor and levofloxacin, were also tested . Twenty S . pneumoniae were passaged for 9 days in the presence of sub-inhibitory concentrations of each antimicrobial agent and MICs determined by NCCLS macro-dilution method . There was a four-fold increase in amoxicillin/clavulanic acid MICs for 2 of 20 isolates . Three of 9 tested against cefaclor, 11 of 13 tested against azithromycin and 9 of 20 tested against levofloxacin showed > or =4-fold increase . Amoxicillin/clavulanic acid was the most stable of the agents tested . Cefaclor MICs were also fairly stable . Azithromycin and levofloxacin MICs were most affected.

Int J Antimicrob Agents, 2004 Aug, 24(2), 125 - 9
Antimicrobial susceptibilities and analysis of genes related to penicillin or macrolide resistance in Streptococcus pneumoniae; Hiramatsu K et al.; One hundred and seventy-seven strains of Streptococcus pneumoniae derived from respiratory specimens between 1987 and 2001 were evaluated for their antimicrobial susceptibilities and distribution of genes related to penicillin and macrolide resistance . Resistance rates tended to be higher for the 1996-2001 isolates than for the 1987-1995 isolates for all beta-lactams tested . For benzylpenicillin the MIC(90) value of the isolates derived between 1996 and 2001 was 1.56 mg/L, while that of strains isolated between 1987 and 1990 was 0.05 mg/L . Furthermore, the number of strains susceptible to macrolides also decreased, but only two strains isolated in 1993 were resistant to levofloxacin of the 177 S . pneumoniae strains tested . When of genes relating to penicillin resistance were analysed using PCR with primers specific to susceptible alleles, although more than 50% of strains from 1987 to 1990 and 1991 to 1995 revealed no mutations in the pbp 1a, 2x and 2b genes, only 30.0% of strains derived between 1996 and 2001 showed no mutations in the pbp gene . Strains having mutations in all three pbp genes (1a, 2x and 2b) by the PCR method increased from only 2.2% in the 1987-1990 derived strains to 27.5% in the 1996-2001 strains . Furthermore, 64.1 and 60.0% of the isolates from 1987 to 1990 and 1991 to 1995, respectively, did not possess either the mefA or ermB by PCR analysis . Conversely, 75.0% of isolates from 1996 to 2001 possessed mefA and/or ermB . These genetic changes may explain the increase in the number of penicillin and macrolide resistant strains . We believe that it is important to evaluate changes in MIC as well as genetic mutations in order to select the most appropriate therapy for S . pneumoniae infections.

Int J Antimicrob Agents, 2004 Aug, 24(2), 95 - 104
A review of clinical failures associated with macrolide-resistant Streptococcus pneumoniae; Rzeszutek M et al.; The emerging reports of clinical failures using macrolides and their associations with macrolide-resistant Streptococcus pneumoniae prompted us to review the literature describing these cases . Thirty-three cases reporting macrolide treatment failure during treatment of pneumococcal infections were available for review . The most prevalent diagnosis (24/27 or 88.8% of available diagnoses) was community-acquired pneumonia (CAP) . Previous medical history included cardiopulmonary disease in eight (24.2%) and immunocompromised states in five (15.1%) patients . The majority, 31/33 (93.9%) of patients received oral macrolide treatment in an outpatient setting . S . pneumoniae was isolated from the blood in 26 (78.8%) of 33 patients, three (9.1%) patients had bacteria present in both blood and cerebrospinal fluid, two (6%) patients grew S . pneumoniae from blood and bronchial washings and two (6%) patients had positive sputum cultures . The MLS(B) phenotype was the most predominant phenotype present in 12 (63.2%) of 19 patients . After failing initial macrolide treatment, 26 (78.8%) of 33 patients received parenteral antibiotic treatment . Of 33 patients admitted to hospital, 29 (87.8%) had their outcome described as 'survived'.

No Shinkei Geka, 2004 May, 32(5), 493 - 9
{A surgically treated case with a ruptured bacterial aneurysm of the middle cerebral arterial bifurcation following occlusion}; Yamaguchi S et al.; A 56-year-old woman with aortic regurgitation (AR) developd a high fever on April 25th, 2003, followed by the sudden onset of left hemiparesis and dysarthria on May 10th, 2003 . MRI and MRA showed cerebral infarction due to occlusion of the right proximal portion of the middle cerebral artery . Streptococcus was isolated from arterial blood culture at the time of admission and cardiac examination such as echocardiography revealed active infective endocarditis . Cerebral angiography on the 31st day after the onset of symptoms demonstrated a fusiform-shaped aneurysm at the occluded M2 portion of the middle cerebral artery . Despite administration of antibiotics, a small subcortical hematoma was observed in the right temporal lobe surrounding the aneurysm on the 35th day . The direct surgery of aneurysmal trapping and resection was subsequently performed to prevent rebleeding . The sylvian fissure and perianeurysmal area were strongly adherent to granulation tissue and blood clot . After exposing the aneurysm, the dilated portion of the vessel was successfully trapped and resected . Other than residual left hemiparesis, the postoperative course was uneventful . Histological examination confirmed bacterial aneurysm due to bacterial embolization originating from infective endocarditis (IE) . We report a rare case having a ruptured bacterial aneurysm of the middle cerebral arterial bifurcation requiring surgery following occlusion due to bacterial embolization after sepsis and meningitis due to infective endocarditis.

Kansenshogaku Zasshi, 2004 Jun, 78(6), 508 - 13
{Analysis of the resistance gene in Streptococcus pneumoniae}; Miyamoto H et al.; Resistance genes were determinded for 81 strains of Streptococcus pneumoniae isolated from Ehime University hospital, during 2002 and 2003 by various clinical material . In penicillin-binding proteins of mutation, there were 74 strains; pbp2x mutation 23 strains (28.4%), pbp2b mutation one strain (1.2%), pbp1a + pbp2x mutations 5 strains (6.2%), pbp2x + pbp2b mutations 18 strains (22.2%) and all mutations 27 strains (33.3%) . As for the result of macrolide resistance genes, there were 67 strains; mefA gene 20 strains (24.7%), ermB gene 46 strains (56.8%) and both gene one strain (1.2%) . In the analysis of gyrA gene and parC gene, 3 strains (3.7%) had both gene mutations, and 26 strains (32.1%) had only parC gene mutation . There was more of an increase than before in isolates, two or more mutation strains with PBPs gene, ermB gene holding strains and the levofloxacin resistance strain . These results suggest that the gyrA gene or parC gene mutation strains hold PBPs gene mutation and macrolide resistance genes in a high rate, and there will be more drug resistance in the future.

Kansenshogaku Zasshi, 2004 Jun, 78(6), 490 - 5
{Efficacy of azithromycin as the empiric therapy in children with community-acquired pneumonia who were isolated macrolide resistant Streptococcus pneumoniae from nasopharynx}; Nariai A et al.; Identification of pathogens in childhood community-acquired pneumonia (CAP) is not easy . However, it is believed that nasopharyngeal colonization of pathogenic bacteria leads to childhood CAP, so the etiology is inferred by the isolates obtained from nasopharynx of children with CAP . Among the pathogens of childhood CAP, Streptococcus pneumoniae (SP) is the most important agent and macrolides resistant SP (MRSP) is increasingly reported . We investigated the characterization of the mechanism of macrolide resistance in isolates of MRSP by the presence of the ermB gene or the mefA gene and clindamycin (CLDM) resistance . In addition, we also assessed the efficacy of azithromycin (AZM) in children with CAP who were isolated MRSP from nasopharynx . During a 6 month period between January and June in 2002, children with CAP who were treated with a 3 day regimen of AZM and isolated SP from nasopharynx were enrolled . Clinical outcome was based on assessment of fever on the fourth day of treatment . MIC measurements were obtained by broth microdilution and interpreted according to NCCLS criteria . 53 patients were enrolled and MRSP were isolated in 41 children . Of 41 MRSP isolates, 25 isolates were identified CLDM resistance . The AZM MIC90 of CLDM resistant MRSP isolates was 128 microg/ml . On the other hand, that of CLDM sensitive MRSP isolates was 8 microg/ml . However, AZM was effective in 20 children isolated CLDM resistant MRSP and 15 out of 16 children isolated CLDM sensitive MRSP . On this background, despite high rates of MRSP in Japan, AZM continues to be clinically effective for the treatment of childhood CAP.

Scand J Infect Dis, 2004, 36(5), 380 - 1
Post-operative meningitis caused by drug-resistant Streptococcus pneumoniae: two case reports; Pancharoen C et al.; We report 2 patients with post-operative meningitis caused by drug-resistant Streptococcus pneumoniae (DRSP), following correction of frontoethmoidal encephalomeningocele in 1 patient and adenotonsillectomy in the other . Both patients responded well to vancomycin plus cefotaxime . DRSP may be colonized in the upper respiratory tract and causes serious infections after surgical operation.

Scand J Infect Dis, 2004, 36(5), 330 - 4
Comparative study of community-acquired pneumonia caused by Streptococcus pneumoniae, Legionella pneumophila or Chlamydia pneumoniae; Sopena N et al.; The objective of this study was to compare epidemiological data and clinical presentation of community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae, Legionella pneumophila or Chlamydia pneumoniae . From May 1994 to February 1996, 157 patients with S . pneumoniae (n = 68), L . pneumophila (n = 48) and C . pneumoniae (n = 41) pneumonia with definitive diagnosis, were prospectively studied . The following comparisons showed differences at a level of at least p < 0.05 . Patients with S . pneumoniae pneumonia had more frequently underlying diseases (HIV infection and neoplasm) and those with C . pneumoniae pneumonia were older and had a higher frequency of chronic obstructive pulmonary disease (COPD), while L . pneumophila pneumonia prevailed in patients without comorbidity, but with alcohol intake . Presentation with cough and expectoration were significantly more frequent in patients with S . pneumoniae or C . pneumoniae pneumonia, while headache, diarrhoea and no response to betalactam antibiotics prevailed in L . pneumophila pneumonia . However, duration of symptoms > or = 7 d was more frequent in C . pneumoniae pneumonia . Patients with CAP caused by L . pneumophila presented hyponatraemia and an increase in CK more frequently, while AST elevation prevailed in L . pneumophila and C . pneumoniae pneumonia . In conclusion, some risk factors and clinical characteristics of patients with CAP may help to broaden empirical therapy against atypical pathogens until rapid diagnostic tests are available.

Scand J Infect Dis, 2004, 36(5), 325 - 9
Invasive pneumococcal disease in Greenland; Christiansen J et al.; INTRODUCTION: The Inuit of Alaska and Canada have a higher incidence of invasive pneumococcal disease than non-inuit . The purpose of the present study was to evaluate incidence and outcome of these infections in Greenland with special reference to pneumococcal serotypes . Study Design: Retrospective study of invasive pneumococcal infections in Greenland in the period 1996-2002 . METHODS: Cases were defined as patients with positive cultures of Streptococcus pneumoniae from blood and/or CSF samples received at the microbiological laboratory of Dronning Ingrids Hospital Nuuk . Isolates were sent to Statens Serum Institut in Copenhagen for serotyping . Medical charts were reviewed . RESULTS: Fifty one cases were identified . The incidence among Inuit was 54 and among non-inuit 17 per 100,000 per year . Twenty one patients were in the age group 35-49 years and 20 in the age group 50-64 years . Twenty patients had meningitis (incidence 6 per 100,000/year) . Seventeen patients died (33%) . The most common serotypes were 1 (6 cases) and 12F (8 cases) . The mortality rate was significantly higher among patients with 12F than among others (p < 0.01) . No patients with serotype 1 died . CONCLUSION: As in Canada and Alaska the incidence of invasive pneumococcal disease, especially meningitis, is high among the Inuit in Greenland . Young and middle aged adults were most frequently affected . Pneumococcal serotype seems to be an important determinant for the outcome of invasive pneumococcal disease.

Pediatrics, 2004 Aug, 114(2), 342 - 7
Developing community-specific recommendations for first-line treatment of acute otitis media: is high-dose amoxicillin necessary?
Garbutt J, St Geme JW 3rd, May A, Storch GA, Shackelford PG.
OBJECTIVES: National recommendations are to use high-dose amoxicillin (80-90 mg/kg per day) to treat uncomplicated acute otitis media (AOM) in children who are at high risk for infection with nonsusceptible Streptococcus pneumoniae (NSSP) . However, high-dose treatment may not be necessary if the local prevalence of NSSP is low . The objective of this study was to estimate the local prevalence of NSSP in children with acute upper respiratory illnesses and to develop community-specific recommendations for first-line empiric treatment of AOM . METHODS: We conducted a cross-sectional prevalence study in the offices of 7 community pediatricians in St Louis, Missouri . S pneumoniae was isolated from nasopharyngeal swabs collected from children who were younger than 7 years and had AOM, nonspecific upper respiratory infection, cough, acute sinusitis, or pharyngitis . Children were excluded from the study when they had received an antibiotic in the previous 4-week period . Parents and providers completed a brief questionnaire to assess risk factors for carriage of NSSP . On the basis of National Clinical Chemistry Laboratory Standards, isolates with a penicillin minimum inhibitory concentration > or =0.12 microg/mL were considered to be nonsusceptible to penicillin (NSSP), and isolates with a penicillin minimum inhibitory concentration >2 microg/mL were categorized as nonsusceptible to standard-dose amoxicillin (35-45 mg/kg per day; NSSP-A) . RESULTS: S pneumoniae was isolated from the nasopharynx of 85 (40%) of 212 study patients (95% confidence interval {CI}: 33%-47%); 41 (48%) of 85 isolates were NSSP (95% CI: 37%-59%), and 6 (7%) were NSSP-A (95% CI: 1.5%-13%) . Among the 212 study patients, the prevalence of NSSP was 19% (95% CI: 14%-25%), and the prevalence of NSSP-A was 3% (95% CI: 0.6%-5%) . Carriage of NSSP was increased in child care attendees compared with nonattendees (29% vs 14%; odds ratio: 2.6; 95% CI: 1.3-5.2) . CONCLUSIONS: In our community, although the prevalence of NSSP among isolates of S pneumoniae identified from the nasopharynx of symptomatic children is high (48%), the probability of NSSP-A infection among symptomatic children is <5% . Our data support a recommendation to treat most children who have uncomplicated AOM with standard-dose amoxicillin . Children who attend child care or have recently received an antibiotic may require treatment with high-dose amoxicillin . Other communities may benefit from a similar assessment of the prevalence of NSSP and NSSP-A.

Am J Obstet Gynecol, 2004 Jun, 190(6), 1493 - 502
Use of microbial cultures and antibiotics in the prevention of infection-associated preterm birth; Klein LL et al.; OBJECTIVE: The purpose of this study was to summarize recent evidence regarding infection-associated preterm birth and to make appropriate recommendations . Antepartum treatment of lower genital tract infection or bacterial colonization has been found to reduce the incidence of preterm birth in the case of asymptomatic bacteriuria and bacterial vaginosis in selected patients but has been proved to be ineffective for vaginal colonization with organisms such as Ureaplasma urealyticum and group B streptococcus . STUDY DESIGN: This is a clinical opinion based on a review of recent data related to 1) the association between lower genital tract infection and preterm birth and 2) antibiotic trials to prevent preterm birth . RESULTS: Antepartum treatment of lower genital tract infection or bacterial colonization has been found to reduce the incidence of preterm birth in the case of asymptomatic bacteriuria and bacterial vaginosis in selected patients, but has been proven to be ineffective for vaginal colonization with organisms such as Ureaplasma urealyticum and group B streptococcus . Large well-designed trials have shown that the routine administration of antibiotics to women with preterm labor and intact membranes is not beneficial; however, antibiotic regimens including macrolides are recommended for preterm premature rupture of the membranes . CONCLUSION: Large well-designed trials have shown that the routine administration of antibiotics to women with preterm labor and intact membranes is not beneficial; however, antibiotic regimens that include macrolides are recommended for preterm premature rupture of the membranes.

Ned Tijdschr Geneeskd . 2004 Jul 3;148(27):1342.
{Diagnostic image (196) . A newborn with fever and a swollen finger}; Vos JM et al.; A 5-day-old girl was presented with monoarthritis of the proximal interphalangeal joint of the right fourth digit, without signs of septic illness or meningitis, due to group B Streptococcus agalactiaePublication Types:

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