Streptococci

J Perinatol, 2003 Jun, 23(4), 265 - 71
Neonatal early-onset group B streptococcal disease in the era of intrapartum chemoprophylaxis: residual problems; Pinto NM et al.; OBJECTIVE: To identify limitations of current strategies for intrapartum prophylaxis of neonatal early-onset group B streptococcal infection . METHODS: Retrospective review of infants with culture-proven early-onset group B streptococcal infection admitted to two nurseries and their mothers from July 1992, when ACOG and AAP guidelines for intrapartum prophylaxis were first issued, through December 2001 . Information was recorded regarding clinical risk factors for early-onset group B streptococcal infection, collection and processing of specimens to assess maternal colonization, delivery of prophylaxis, duration of hospitalization before delivery, and outcome . RESULTS: Among 92 infants with early-onset group B streptococcal infection admitted from 23 institutions, 68 had received no intrapartum prophylaxis . Of these 68 who received no prophylaxis, 34 had identifiable risk factors before delivery (32 clinical, two positive maternal culture), while 34 had no risk factors . Prenatal culture for group B streptococcal colonization was performed in 22 of these women . Of the 18 cultures that were negative for group B streptococcus, 15 were obtained using suboptimal culture technique or were collected more than 6 weeks before delivery . Of the 68 with no prophylaxis, 14 required extracorporeal membrane oxygenation and three died . Of the 24 who received some intrapartum prophylaxis, nine had received >/=two doses for >/=4 hours immediately before delivery . Among the 24 receiving some intrapartum prophylaxis, two required extracorporeal membrane oxygenation and one died . No deaths occurred in those who received >4 hours of prophylaxis, although one such infant required extracorporeal membrane oxygenation . After the CDC guidelines were issued in May 1996, there was a decrease both in the number of cases of early-onset group B streptococcal infection (56 versus 36) as well as in the number with clinical risk factors but no intrapartum prophylaxis (24/56 (43%) versus 5/28 (18%)) . CONCLUSIONS: The use of clinical risk factors alone will inevitably result in missed opportunity for intrapartum antibiotic prophylaxis . With maternal screening, false-negative results will be reduced but not necessarily eliminated by assuring that specimens are obtained from proper sites using selective media within 6 weeks of delivery . Better strategies are needed to assure timely administration when prophylaxis is indicated . The nine neonates with early-onset group B streptococcal infection despite intrapartum antibiotics for the recommended duration illustrate that disease may occur even when guidelines are implemented appropriately.

Biochem Soc Trans, 2003 Jun, 31(Pt 3), 716 - 8
Immunoglobulin-binding domains: Protein L from Peptostreptococcus magnus; Housden NG et al.; Protein L is a multidomain cell-wall protein isolated from Peptostreptococcus magnus . It belongs to a group of proteins that contain repeated domains that are able to bind to Igs without stimulating an immune response, the most characterized of this group being Protein A ( Staphylococcus aureus ) and Protein G ( Streptococcus ) . Both of these proteins bind predominantly to the interface of C(H)2-C(H)3 heavy chains, while Protein L binds exclusively to the V(L) domain of the kappa -chain . The function of these proteins in vivo is not clear but it is thought that they enable the bacteria to evade the host's immune system . Two binding sites for kappa -chain on a single Ig-binding domain from Protein L have recently been reported and we give evidence that one site has a 25-55-fold higher affinity for kappa -chain than the second site.

J Med Chem, 2003 Jun 5, 46(12), 2304 - 12
Novel dihydrofolate reductase inhibitors . Structure-based versus diversity-based library design and high-throughput synthesis and screening; Wyss PC et al.; Novel 2,4-diaminopyrimidines bearing N,N-disubstituted aminomethyl residues at the 5-position were designed as dihydrofolate reductase (DHFR) inhibitors . These compounds were obtained by treatment of 1-{(2,4-diamino-5-pyrimidinyl)methyl}pyridinium bromide with secondary amines in a polar solvent and in the presence of triethylamine at room temperature . The procedure was found to be very efficient and suitable for application in high-throughput synthesis . In addition, we found that high-throughput screening for enzymatic and in vitro antibacterial activity could be performed on crude reaction mixtures, thus avoiding any purification step . Over 1200 proprietary secondary amines were selected for high-throughput synthesis, based on structural and diversity-related criteria, and the resulting products were submitted to high-throughput screening . A greater number of hits, and significantly more active compounds, were obtained through structure-based library design than through diversity-based library design . Different classes of inhibitors of DHFR were identified in this way, including compounds derived from di-, tri-, and tetracyclic amines . In general, these products showed high activity against the enzymes derived from both TMP-sensitive and TMP-resistant Streptococcus pneumoniae . Some compounds possessed appreciable selectivity for the bacterial over the human enzyme, whereas other compounds were not at all selective . In most cases, active enzyme inhibitors also displayed antibacterial activity.

FEMS Immunol Med Microbiol, 2003 Jun 10, 37(1), 53 - 7
Protective efficacy of PspA (pneumococcal surface protein A)-based DNA vaccines: contribution of both humoral and cellular immune responses; Miyaji EN et al.; Streptococcus pneumoniae is a major public health problem and new strategies for the development of cost-effective alternative vaccines are important . The use of protein antigens such as PspA (pneumococcal surface protein A) is a promising approach to increase coverage at reduced costs . We have previously described the induction of a strong antibody response by a DNA vaccine expressing a C-terminal fragment of PspA . Fusion of this fragment with the cytoplasmic variant of SV40 large T-antigen (CT-Ag) caused reduction in specific interferon-gamma produced by stimulated spleen cells . In this work we show that the DNA vaccine expressing the C-terminal region of PspA elicits significant protection in mice against intraperitoneal challenge with a virulent strain of S . pneumoniae . Furthermore, fusion with CT-Ag completely abrogated the protection elicited by DNA immunization with this fragment . In this case, protection did not correlate with total anti-PspA antibody production nor with total IgG2a levels . The anti-PspA sera obtained from both constructs showed equivalent opsonic activity of pneumococci, indicating that the antibodies produced were functional . We could, though, observe a correlation between a lower IgG1:IgG2a ratio, which is indicative of a stronger bias towards Th1 responses, and protection . We also show that a vector expressing the most variable N-terminal alpha-helical region induces higher antibody formation, with increased protection of mice against intraperitoneal challenge with a more virulent strain of S . pneumoniae . As a whole, these results indicate that antibodies elicited against PspA would not be solely responsible for the protection induced by DNA vaccination and that cell-mediated immune responses could also be involved in protection against pneumococcal sepsis.

FEMS Microbiol Lett, 2003 May 28, 222(2), 263 - 71
Novel protein vaccine candidates against Group B streptococcal infection identified using alkaline phosphatase fusions; Hughes MJ et al.; Using an alkaline phosphatase-based genetic screening method, we identified a number of proteins that are potentially located on the outer surface of Group B streptococcus (Streptococcus agalactiae) . In an enzyme-linked immunosorbent assay, antisera raised against two of the proteins, the streptococcal yutD homologue and a subunit of an ABC transporter, recognised clinically important serotypes of Group B streptococcus . In a neonatal rat model, purified IgG from the sera conferred significant levels of protection against a lethal challenge infection . The proteins identified show potential as protein subunit candidates for vaccines against Group B streptococcal disease in neonates.

FEMS Microbiol Lett, 2003 May 28, 222(2), 193 - 7
Molecular and biochemical analysis of the system regulating the lytic/lysogenic cycle in the pneumococcal temperate phage MM1; Obregon V et al.; The temperate phage MM1 forms stable lysogens in Streptococcus pneumoniae . We report here the first characterization of the lysogenic control region in Pneumococcus which contains two functional divergent promoters (P(R) and P(L)) . MM1 encodes a 14-kDa cI protein (CI) that appears to be responsible for maintaining the lysogenic state in Pneumococcus since it prevents elongation of the transcripts controlled by P(R) and P(L).

BMC Gastroenterol . 2003 May 24;3(1):9.
Spectrum and antibiotic sensitivity of bacteria contaminating the upper gut in patients with malabsorption syndrome from the tropics; Ghoshal U et al.; BACKGROUND: Various causes of malabsorption syndrome (MAS) are associated with intestinal stasis that may cause small intestinal bacterial overgrowth (SIBO) . Frequency, nature and antibiotic sensitivity of SIBO in patients with MAS are not well understood . METHODS: Jejunal aspirates of 50 consecutive patients with MAS were cultured for bacteria and colony counts and antibiotic sensitivity were performed . Twelve patients with irritable bowel syndrome were studied as controls . RESULTS: Culture revealed growth of bacteria in 34/50 (68%) patients with MAS and 3/12 controls (p < 0.05) . Colony counts ranged from 3 x 10(2) to 10(15) (median 10(5)) in MAS and 100 to 1000 (median 700) CFU/ml in controls (p 0.003) . 21/50 (42%) patients had counts GreaterEqual;105 CFU/ml in MAS and none of controls (p < 0.05) . Aerobes were isolated in 34/34 and anaerobe in 1/34 . Commonest Gram positive and negative bacteria were Streptococcus species and Escherichia coli respectively . The isolated bacteria were more often sensitive to quinolones than to tetracycline (ciprofloxacin: 39/47 and norfloxacin: 34/47 vs . tetracycline 19/47, <0.01), ampicillin, erythromycin and co-trimoxazole (21/44, 14/22 and 24/47 respectively vs . tetracycline, p = ns) . CONCLUSIONS: SIBO is common in patients with MAS due to various causes and quinolones may be the preferred treatment . This needs to be proved further by a randomized controlled trial.

An Med Interna, 2003 Apr, 20(4), 179 - 82
{Utility of anaerobic blood cultures in extra-hospitalary bacteremias}; Ruiz-Giardin JM et al.; OBJECTIVE: To compare the rentability of anaerobic hemocultures with aerobic cultures in patients suffering bacteremia, trying to analyze the rentability of anaerobic cultures . METHODS: There were analyzed all the hemocultures taken by medical decision for one month . There were taken three extractions by patient in different venopunctures points . In each extraction was taken 10 ml (5 ml in aerobic bottle, and 5 ml in anaerobic bottle) . There were compared microorganism isolated in aerobic bottles and anaerobic bottles . Three physician analyzed all the clinical dates of the patients with positive hemocultures and classified them as negatives, contaminants and significant . RESULTS: There were taken hemocultures of 180 patients . There were analyzed 152 hemocultures groups (3 extractions aerobic-anaerobic), without studying 28 owe to not following the study protocol 24 (13.3%) or because of not possibility of studying clinical story 4 (2.2%) . Aerobic extractions: Negatives 91 (59.86%), contaminants 36 (23.68%), significant with or without contaminant 25 (16.44%) . Anaerobic extractions: Negatives 127 (83.5%), contaminants 2 (1.31%); significant with or without contaminant 23 (15.13%) . There are 6 (8.6%) significant positive isolated in anaerobic bottles, that were negative in aerobic bottles, and are: 3 E . coli, 1 K . pneumoniae, 1 Peptostreptococcus sp, 1 Bacteroides sp, and over the total significant isolated (31) are the 19.35% . Both anaerobic bacteremias were clinically suspected . Contaminant microorganism more frequently isolated in aerobic bottles was Staphylococcus sp, 25 cases (69.44% of all contaminants) . Significant microorganism more frequently isolated was E . coli (in anaerobic bottles too) in 12 cases (38.70%) of all significant isolated, following by Streptococcus pneumoniae with 4 cases (12.9%) . CONCLUSIONS: We recommend collection of one aerobic and one anaerobic blood culture bottle per blood culture set because the global rentability of hemocultures is increased significantly.

Zhonghua Er Bi Yan Hou Ke Za Zhi, 2002 Feb, 37(1), 23 - 6
{A comparative experimental study between recombinant active gene 1-deficient mice and C57BL/6 mice model of acute bacterial rhinosinusitis}; Xie M; OBJECTIVE: To explore the infective course of acute bacterial rhinosinusitis in recombinent active gene 1 (Rag 1)-defecient mice (Rag1) and C57BL/6 mice (C57) and the difference between them after intranasal streptococcus pneumoniae inoculation . METHODS: Ten mice of each strain (Rag1 and C57) received Streptococcus pneumoniae strain T59, ATCC 49,619 suspended in trypticase soy broth, and controls (two mice for each strain) received trypticase soy broth alone . After 2, 5, 10 and 14 days, nasal lavage cultures were obtained and then the mice were killed . The heads were embedded with paraffin and serial sections were made for histological analysis . The percentage of sinus cavity occupied by neutrophil cluster (% cluster) and the number of polymorphonuclear leukocytes per square millimeter of sinus mucosa (PMN/mm2) were calculated by the use of a computer-aided microscope in conjunction with a reconstruction and image analysis system . RESULTS: % Cluster and PMN/mm2 in infected mice both of Rag1 and C57 appeared to peak on five and ten days separately, which were significantly heavier than those in controls(P < 0.05) . The infection in C57 decreased by two weeks . But in contrast to C57, the infection in Rag1 had not been controlled and Streptococcus pneumoniae were still seen in the nasal lavage culture by two weeks . This difference between infected Rag1 and infected C57 was significant at P < 0.05 . CONCLUSION: Acute bacterial rhinosinusitis in Rag1 and C57 mice were successfully induced by intranasal inoculation of streptococcus pneunoniae . This bacterial infection in C57 could be controlled completely and rapidly . In contrast, Rag1 failed to control rhinosinusitis and had a tendency to chronic inflammation, suggesting that T- and B-cell-dependent immunity was important for clearance of bacteria from rhinosinus and gene knockout mice was a convenient tool for investigation of the pathogenesis of experimental rhinosinusitis.

Zhonghua Er Bi Yan Hou Ke Za Zhi, 2000 Apr, 35(2), 113 - 6
{A novel method for screening anti-inner ear autoantibody in patients with autoimmune diseases}; Zou J et al.; OBJECTIVE: To appraise the clinical value of a newly established method, rapid electric field immobilizing liquid phase molecule dot blot analysis (REILMD), for screening anti-inner ear autoantibody in patients with autoimmune diseases . METHODS: Seventy-one patients with 11 kinds of autoimmune diseases were chosen for the study . Both the general immunity and autoantibodies were tested . In the processes of detection of anti-inner ear autoantibody, REILMD was used for screening, and then the Western blot was used to define the molecular weight of inner ear antigen recognized by the positive autoantibody . RESULTS: Acceleration of erythrocyte sedimentation rate (ES), positive rheumatoid factor (RF), increases in C reactive protein (CRP), IgG and circulating immune complex (CIC) were found in most cases with rheumatoid arthritis (RA) and systemic lupus erythematodes (SLE) . Some of these patients had increased IgA, IgM and C4 . Two of 16 RA had anti-double-stranded DNA (dsDNA) and anti-mitochondria and 4/16 had anti-nucleus antibodies . Eleven of 16 SLE had antinucleus, 7/13 had anti-ribonucleoprotein (RNP), anti-Sjogren syndrome A (SSA) and anti-dsDNA, 3/13 had anti-smooth muscle (Sm) and 1/13 had anti-DNA topoisomerase I (Scl)-70, striated muscle and stomach acid cell antibodies . No autoantibody was detected in AS . Anti-inner ear autoantibody existed in 9 out of 71 patients (13%) with autoimmune diseases, in 2 of 21 patients (10%) with sudden deafness and only in 1 of 48 control subjects (2%, coronary heart disease) . The anti-inner ear autoantibody was positive in 5 of 16 (31%) patients with SLE and 1 each in RA, AS, Behset's disease and streptococcus infection syndrome . In patients with positive anti-inner ear antibody, 67% had anti-nucleus antibody, 50% had anti-RNP and dsDNA antibody . The molecules recognized by the positive anti-inner ear antibody were defined as 52,000, 36,000, 31,000 and 15,000 molecules of inner ear antigen . CONCLUSION: REILMD is a feasible and easy method for screening anti-inner ear autoantibody . Several autoimmune diseases, particularly SLE, may be implicated in damage to the inner ear.

J Chromatogr B Analyt Technol Biomed Life Sci, 2003 Jun 25, 790(1-2), 365 - 72
Preparative purification of soybean agglutinin by affinity chromatography and its immobilization for polysaccharide isolation; Franco-Fraguas L et al.; Optimized procedures for the affinity purification of soybean agglutinin (SBA) from soybean flour, and its further immobilization, were developed . Lectin purification on galactosyl-Sepharose yielded 44.5+/-3.5 mg of pure SBA/50 g of flour . To prepare SBA adsorbents, the lectin was immobilized onto 1-cyano-4-(dimethylamino)pyridinium tetrafluoroborate (CDAP) activated Sepharose with high yields (77%) . Feasibility of the use of this improved SBA adsorbent for affinity purification of Streptococcus pneumoniae capsular polysaccharides from strain 14 (CPS-14) at laboratory scale was demonstrated . Using SBA-Sepharose adsorbent (7.0 mg lectin per ml), amounts of 6.3 mg of pure CPS-14 per cycle were produced, the adsorbent being reused up to four times without loss of capacity.

Paediatr Drugs, 2003, 5(6), 419 - 29; discussion 430-1
Linezolid: in infants and children with severe Gram-positive infections; Lyseng-Williamson KA et al.; Linezolid is an oxazolidinone antibacterial agent that has inhibitory activity against a broad range of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae . The systemic clearance and, therefore, the area under the plasma concentration-time curve and elimination half-life of linezolid change with increasing age in pediatric patients . With the exception of pre-term neonates aged <1 week, systemic clearance is more rapid in pediatric patients aged 0-11 years than in adolescents . The pharmacokinetic profile of linezolid is similar in adolescents and adults . Linezolid was as effective as vancomycin in the treatment of pediatric patients with Gram-positive infections (clinical cure rate 89.3% vs 84.5%), and as effective as cefadroxil in the treatment of children and adolescents with Gram-positive uncomplicated skin and skin structure infections (91.0% vs 90.0%) in the clinically evaluable population of two randomized, comparator-controlled trials . The clinical cure rate with linezolid was 92.4% in a noncomparative trial in hospitalized pediatric patients with community-acquired pneumonia . All patients with proven pneumococcal pneumonia were considered cured . Linezolid is generally well tolerated . The most common drug-related adverse events in the comparator-controlled trials were diarrhea, nausea, and headache; most events were mild to moderate in severity.

Eur Respir J, 2003 May, 21(5), 779 - 84
Chlamydia species as a cause of community-acquired pneumonia in Canada; Marrie TJ et al.; Chlamydia pneumoniae has been implicated as a cause of community-acquired pneumonia (CAP) in several studies . However, there has been no comprehensive study of the role of Chlamydia species (C . pneumoniae, C . psittaci (avian and feline strains) and C . pecorum) as a cause of CAP . The aim of the present study was to determine the role of C . pneumoniae, C . psittaci and C . pecorum as causes of CAP . A prospective cohort observational study of CAP was conducted at 15 teaching centres in eight Canadian provinces between January 1996-October 1997 . Acute (n=539) and convalescent (n=272) serum samples were obtained for determination of antibody titres to C . pneumoniae, C . psittaci, C . pecorum, C . trachomatis, Mycoplasma pneumoniae, Legionella pneumophila serogroups I-VI, Streptococcus pneumoniae and various respiratory viruses . Twelve of 539 (2.2%) patients had acute C . pneumoniae pneumonia and an additional 32 (5.9%) had possible acute infection . C . pneumoniae was the sole pathogen in 16 of 42 (38.1%) of these patients . The most common copathogens were S . pneumoniae, respiratory syncytial virus and influenza virus type A . C . pneumoniae pneumonia patients were older and more likely to show congestive heart failure compared to bacteraemic S . pneumoniae patients . The latter had a lower mean diastolic blood pressure, a higher white blood cell count and a lower arterial carbon dioxide tension . Two patients had antibody titres suggestive of recent infection with the feline strain of C . psittaci . Although numerically Chlamydia pneumoniae is an important cause of community-acquired pneumonia, no distinctive clinical features associated with this pathogen were detected in the present study . Feline Chlamydia psittaci may cause a few cases of community-acquired pneumonia . Avian Chlamydia psittaci should be considered only if there is a compatible epidemiological history.

Prog Urol, 2003 Apr, 13(2), 306 - 7
{Pre-pubic abscess of unknown cause}; Peyromaure M et al.; The authors report a case of prepubic abscess in a young man presenting with pain . Surgical exploration revealed a group A Streptococcus abscess . The cause of this abscess was not determined.

Brain Res, 2003 Jun 27, 976(2), 139 - 48
Impaired cortical energy metabolism but not major antioxidant defenses in experimental bacterial meningitis; Ghielmetti M et al.; The loss of soluble brain antioxidants and protective effects of radical scavengers implicate reactive oxygen species in cortical neuronal injury caused by bacterial meningitis . However, the lack of significant oxidative damage in cortex {J . Neuropathol . Exp . Neurol . 61 (2002) 605-613} suggests that cortical neuronal injury may not be due to excessive parenchymal oxidant production . To see whether this tissue region exhibits a prooxidant state in bacterial meningitis, we examined the state of the major cortical antioxidant defenses in infant rats infected with Streptococcus pneumoniae . Adenine nucleotides were co-determined to assess possible changes in energy metabolism . Arguing against heightened parenchymal oxidant production, the high NADPH/NADP(+) ratio ( approximately 3:1) and activities of the major antioxidant defense and pentose phosphate pathway enzymes remained unchanged at the time of fulminant meningitis . In contrast, cortical ATP, ADP and total adenine nucleotides were on average decreased by approximately 25% . However, energy depletion did not lead to a significant decrease in adenylate energy charge (AEC) . ATP depletion was likely a consequence of metabolic degradation, since it correlated with both the loss of total adenine nucleotides and accumulation of purine degradation products . Furthermore, the loss of ATP and decrease in AEC correlated significantly with the extent of neuronal injury . These results strongly suggest that energy depletion rather than parenchymal oxidative damage is involved in the observed cortical neuronal injury.

Med Arh, 2002, 56(3 Suppl 1), 51 - 3
{Incidence of early-onset neonatal sepsis caused by group B Streptococcus at the Pediatric Clinic of the University Clinical Center in Sarajevo}; Maksic H et al.; Group B Streptococcus (GBS) is the main ethiological agent of neonatal sepsis in the developed countries . Because of high mortality rate American College of Obstetrics and Gynaecologists and Centers for Disease Control published recommendation for prevention of neonatal GBS infection . Program recommends screening of all pregnant women for anogenital GBS infection including intrapartum treatment of pregnant women at high risk, with penicillin or ampicillin . Clindamicin or erythromicin may be used for women allergic to penicillin . Since there is no detailed informations of early-onset neonatal GBS infection in our country, we investigated its incidence in Pediatric Clinic in Sarajevo, from December 1999 (when first case of early-onset GBS infection in last decade was diagnosed) to August 2002 . During that period 7 neonates with early-onset GBS infection were identified (incidence 0.52 per 1000 livebirths) . Four of seven sick newborns died, 2/7 survived with severe neurological sequelae and only one female newborn survived without deficits . In the same period we registered 36 (2.4%) GBS colonised neonates out of 1530 admitted neonates . The number probably is higher because of discharge GBS colonized asymptomatic neonates from Maternity as a healthy to home . Results of this study intend the necessity of implementation guidelines for GBS prevention since early onset GBS infection is becoming as an increasing problems in our population.

Genes Immun, 2003 Jun, 4(4), 283 - 8
Polymorphisms in lymphotoxin alpha and CD14 genes influence TNFalpha production induced by Gram-positive and Gram-negative bacteria; Temple SE et al.; Improved understanding of how host genetic variation affects resistance to microbial pathogens could lead to better treatment and/or prevention of infectious diseases . The lymphotoxin alpha (LTA)+250 and CD14-159 polymorphisms are associated with differences in susceptibility or outcome to several infections . We stimulated peripheral blood mononuclear cells (PBMC) from 22 healthy individuals with purified lipopolysaccharide (LPS), heat-killed Escherichia coli or Streptococcus pneumoniae . TNF alpha intracellular protein levels were measured by flow cytometry and mRNA was quantitated by RT-PCR . TNF alpha mRNA levels were higher in LTA+250GG subjects after 4 h incubation with LPS compared with LTA+250AA (T test, P=0.001) . In contrast, after 8 h incubation with S . pneumoniae, there was slightly more TNF alpha mRNA in cells from LTA+250AA subjects . After 4 h incubation with LPS or E . coli, CD14-159TT subjects had higher TNF alpha mRNA levels than CD14-159CC (P=0.05, 0.033, respectively) . Neither polymorphism affected the proportion of cells expressing intracellular TNF alpha protein . This suggests that the polymorphisms affected transcription and that other regulatory mechanisms affect production of TNF alpha protein . The effect of these two polymorphisms on TNF alpha mRNA production is stimulus dependent, with opposite effects observed for Gram-positive and Gram-negative stimuli.

Infect Immun, 2003 Jun, 71(6), 3206 - 12
Mutation of luxS of Streptococcus pneumoniae affects virulence in a mouse model; Stroeher UH et al.; The LuxS protein is required for the biosynthesis of the type 2 autoinducer (AI-2), which is involved in quorum sensing in a wide range of bacterial species . We have determined the effects of a defined luxS mutation on the virulence of Streptococcus pneumoniae . Although the luxS mutant displayed reduced virulence relative to its wild-type parent, the type 2 strain D39, it was by no means avirulent in a mouse model . After intranasal administration, the luxS mutant was able to colonize the nasopharynx of the mouse as efficiently as the wild type . However, it was less able to spread from the nasopharynx to the lungs or the blood . Intraperitoneal coadministration studies indicated that the luxS mutant was less fit and was readily outcompeted by wild-type D39 . However, when administered on its own by this route, the mutant was able to proliferate and cause fatal systemic disease, albeit at a lower rate than the wild type . Western blot analysis of whole-cell lysates of the mutant and its parent did not reveal any differences in the levels of several well-characterized virulence proteins . However, analysis of Coomassie blue-stained protein profiles after separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that mutation of luxS had pleiotropic effects on protein expression in all cellular compartments . This is consistent with the product of luxS having a regulatory role in S . pneumoniae . This is the first report of a direct role for luxS (and by inference, AI-2) in the virulence of a gram-positive pathogen . However, the fact that mutagenesis of luxS does not completely attenuate S . pneumoniae has implications for the possible use of AI-2 antagonists for treatment of pneumococcal infections.

Infect Immun, 2003 Jun, 71(6), 3028 - 33
A fluoroquinolone induces a novel mitogen-encoding bacteriophage in Streptococcus canis; Ingrey KT et al.; This study investigated whether the recently recognized emergence of canine streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis (NF) might be partly attributed to the use of fluoroquinolones to treat Streptococcus canis infections in dogs . Both mitomycin and the fluoroquinolone enrofloxacin caused bacteriophage-induced lysis of S . canis strain 34, an isolate from a case of canine STSS and NF . Fluoroquinolone-evoked, bacteriophage-induced lysis occurred over a range of concentrations similar to those that would occur after treatment of dogs with these agents . To search for a possible bacteriophage-encoded streptococcal superantigen gene(s), a library of the 36.5 (+/-1.1)-kb bacteriophage, designated phisc1, was made by ligating 3- to 7-kb Tsp5091-digested phisc1 fragments into an EcoRI-digested lambdaZapII vector . Recombinants were screened for mitogenic activity by using canine peripheral blood lymphocytes . Of 800 recombinants screened, 11 recombinants with mitogenic effects were identified, and their inserts were sequenced . The highest homology of 11.6 kb of sequenced phisc1 DNA was to the completely sequenced Streptococcus pneumoniae bacteriophage MM1 . Seven of the 11 phisc1 sequenced inserts contained a 552-bp open reading frame, scm, with 27% amino acid similarity to pokeweed (Phytolacca americana) mitogen . PCR showed this gene to be present in 22 of 23 S . canis isolates tested . Quantitative reverse transcription-PCR showed that bacteriophage induction was associated with a 58-fold enhancement of expression of this gene relative to that in a noninduced culture of a similar age . The presence of this gene on a fluoroquinolone-induced bacteriophage may explain the association observed between fluoroquinolone use in dogs and the development of canine STTS and NF.

Antimicrob Agents Chemother, 2003 Jun, 47(6), 1984 - 7
Linezolid and vancomycin, alone and in combination with rifampin, compared with moxifloxacin against a multidrug-resistant and a vancomycin-tolerant Streptococcus pneumoniae strain in an in vitro pharmacodynamic model; Cha R et al.; Potential alternatives, including linezolid, adjunctive rifampin, and moxifloxacin, were evaluated against vancomycin-tolerant (P9802-020) and vancomycin-susceptible clinical isolates of Streptococcus pneumoniae in an in vitro pharmacodynamic model . Vancomycin exhibited maximal killing of 2-log(10) CFU/ml against P9802-020 . Linezolid, moxifloxacin, and linezolid plus rifampin exhibited 99.9% killing against both isolates . These alternatives should be considered for further evaluation against vancomycin-tolerant S . pneumoniae.

Antimicrob Agents Chemother, 2003 Jun, 47(6), 1976 - 8
Lack of vancomycin tolerance in Streptococcus pneumoniae strains isolated in Barcelona, Spain, from 1999 to 2001; Ortega M et al.; To evaluate the incidence of vancomycin tolerance among Streptococcus pneumoniae isolates, we performed killing curve studies with 633 isolates . The penicillin MIC was > or = 0.12 mg/liter for 481 (76%) of the isolates . All strains were susceptible to vancomycin . Killing curve studies were performed with a vancomycin concentration of 2.5 mg/liter . The Tupelo strain was used for quality control . No vancomycin-tolerant strain was detected.

Antimicrob Agents Chemother, 2003 Jun, 47(6), 1867 - 74
Antimicrobial resistance in respiratory tract Streptococcus pneumoniae isolates: results of the Canadian Respiratory Organism Susceptibility Study, 1997 to 2002; Zhanel GG et al.; A total of 6,991 unique patient isolates of Streptococcus pneumoniae were collected from October 1997 to June 2002 from 25 medical centers in 9 of the 10 Canadian provinces . Among these isolates, 20.2% were penicillin nonsusceptible, with 14.6% being penicillin intermediate (MIC, 0.12 to 1 microg/ml) and 5.6% being penicillin resistant (MIC, > or =2 microg/ml) . The proportion of high-level penicillin-resistant S . pneumoniae isolates increased from 2.4 to 13.8% over the last 3 years of the study, and the proportion of multidrug-resistant S . pneumoniae isolates increased from 2.7 to 8.8% over the 5-year period . Resistant rates (intermediate and resistant) among non-beta-lactam agents were as follows: macrolides, 9.6 to 9.9%; clindamycin, 3.8%; doxycycline, 5.5%; chloramphenicol, 3.9%; and trimethoprim-sulfamethoxazole, 19.0% . Rates of resistance to non-beta-lactam agents were higher among penicillin-resistant strains than among penicillin-susceptible strains . No resistance to vancomycin or linezolid was observed; however, 0.1% intermediate resistance to quinupristin-dalfopristin was observed . The rate of macrolide resistance (intermediate and resistant) increased from 7.9 to 11.1% over the 5 years . For the fluoroquinolones, the order of activity based on the MICs at which 50% of isolates are inhibited (MIC(50)s) and the MIC(90)s was gemifloxacin > clinafloxacin > trovafloxacin > moxifloxacin > grepafloxacin > gatifloxacin > levofloxacin > ciprofloxacin . The investigational compounds ABT-773 (MIC(90), 0.008 microg/ml), ABT-492 (MIC(90), 0.015 microg/ml), GAR-936 (tigecycline; MIC(90), 0.06 microg/ml), and BMS284756 (garenoxacin; MIC(90), 0.06 micro g/ml) displayed excellent activities . Despite decreases in the rates of antibiotic consumption in Canada over the 5-year period, the rates of both high-level penicillin-resistant and multidrug-resistant S . pneumoniae isolates are increasing in Canada.

Antimicrob Agents Chemother, 2003 Jun, 47(6), 1777 - 83
Macrolide resistance by ribosomal mutation in clinical isolates of Streptococcus pneumoniae from the PROTEKT 1999-2000 study; Farrell DJ et al.; Sixteen (1.5%) of the 1,043 clinical macrolide-resistant Streptococcus pneumoniae isolates collected and analyzed in the 1999-2000 PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) study have resistance mechanisms other than rRNA methylation or efflux . We have determined the macrolide resistance mechanisms in all 16 isolates by sequencing the L4 and L22 riboprotein genes, plus relevant segments of the four genes for 23S rRNA, and the expression of mutant rRNAs was analyzed by primer extension . Isolates from Canada (n = 4), Japan (n = 3), and Australia (n = 1) were found to have an A2059G mutation in all four 23S rRNA alleles . The Japanese isolates additionally had a G95D mutation in riboprotein L22; all of these originated from the same collection center and were clonal . Three of the Canadian isolates were also clonal; the rest were not genetically related . Four German isolates had A2059G in one, two, and three 23S rRNA alleles and A2058G in two 23S rRNA alleles, respectively . An isolate from the United States had C2611G in three 23S rRNA alleles, one isolate from Poland had A2058G in three 23S rRNA alleles, one isolate from Turkey had A2058G in four 23S rRNA alleles, and one isolate from Canada had A2059G in two 23S rRNA alleles . Erythromycin and clindamycin resistance gradually increased with the number of A2059G alleles, whereas going from one to two mutant alleles caused sharp rises in the azithromycin, roxithromycin, and rokitamycin MICs . Comparisons of mutation dosage with rRNA expression indicates that not all alleles are equally expressed . Despite their high levels of macrolide resistance, all 16 isolates remained susceptible to the ketolide telithromycin (MICs, 0.015 to 0.25 microg/ml).

Curr Infect Dis Rep, 2003 Jun, 5(3), 230 - 237
Drug-resistant Streptococcus pneumoniae in Community-acquired Pneumonia; Henry M et al.; The emergence of Streptococcus pneumoniae isolates resistant to not only penicillin, but to other antipneumococcal agents as well, has major public health implications . Drug-resistant S . pneumoniae are distributed worldwide, and resistance has become increasingly prevalent in the United States within the past decade . The relevance of resistance, particularly to the beta-lactams, to treatment outcome has been subject to debate . Pneumonia due to intermediate-level-resistant penicillin-resistant isolates of S . pneumoniae appears to be adequately treated by beta-lactam agents . Interpretation of resistance reports, which may be based on achievable cerebrospinal fluid levels of drug, may depend on the clinical setting, and efforts are underway to adjust breakpoints so that reports are more easily applicable to clinical practice . Infectious Diseases Society of America and American Thoracic Society guidelines, as well as others, for community-acquired pneumonia have addressed the impact of drug-resistant S . pneumoniae on antimicrobial selection.

J Antibiot (Tokyo), 2003 Mar, 56(3), 226 - 31
Nocathiacins, new thiazolyl peptide antibiotics from Nocardia sp . I . Taxonomy, fermentation and biological activities; Li W et al.; Thiazolyl peptide antibiotics, nocathiacin I, II and III, were identified in a culture of Nocardia sp . WW-12651 (ATCC 202099) . They exhibit potent in vitro activity (ng/ml) against a wide spectrum of gram-positive bacteria, including multiple-drug resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), multi-drug resistant Enterococcus faecium (MREF) and fully penicillin-resistant Streptococcus pneumoniae (PRSP), and demonstrate excellent in vivo efficacy in a systemic Staphylococcus aureus infection mice model.

J Int Acad Periodontol, 2003 Apr, 5(2), 35 - 40
Antibacterial activity of synthetic human B defensin-2 against periodontal bacteria; Mineshiba F et al.; The oral epithelium is continuously exposed to a variety of microbial challenges that can cause infectious diseases such as periodontal disease . Human B Defensin-2 (hBD-2) is a cationic antimicrobial peptide with low molecular weight, which is inducible from oral epithelial cells upon either bacterial infection or stimulation with inflammatory cytokines . This peptide has a broad antimicrobial spectrum that includes gram-positive bacteria, gram-negative bacteria, and fungi . Therefore, it is thought that hBD-2 plays an important role as one of natural immunities to bacterial infection . However, its activity is inhibited by body fluids such as serum . The aim of this study was to assess the antibacterial activity of synthetic hBD-2 against oral bacteria in the presence of saliva or serum . The antibacterial activity of synthetic hBD-2 was tested against Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Streptococcus mutans, and Escherichia coli . Antibacterial broth assay and diffusion assay were performed in vitro . The antibacterial activity of hBD-2 was approximately equal to that of minocycline at equimolar concentrations . Furthermore, the activity of hBD-2 remained at 60% in the presence of 80% saliva, whereas no activity remained in the presence of 20% serum . Our results suggest the possibility that synthetic hBD-2 could be useful to prevent infection by periodontal bacteria.

An Sist Sanit Navar, 2003 Jan-Apr, 26(1), 27 - 33
{Resistance to penicillin and other antimicrobials in 103 clinical isolations of Streptococcus pneumoniae (2000-2001)}; Garcia-Irure JJ et al.; BACKGROUND: To determine in our hospital the sensitivity of isolations of Streptococcus pneumoniae to penicillin, as well as to analyse the association of resistance to penicillin and other antimicrobials and the activity of cefotaxime and cefepime in pencillin resistant strains of Streptococcus pneumoniae . METHODS: The sensitivity was determined on 103 isolations of Streptococcus pneumoniae, from clinical samples from the years 2000-2001, to penicillin, eritromycine, cloramfenicol, tetracycline, cotrimoxazol, cefotaxime, cefepime and levofloxacine . RESULTS: Sixty-eight percent of the isolations were sensitive to penicillin, while some 32% of the isolated strains of Streptococcus pneumoniae were penicillin resistant, with 7.7% showing a high degree of resistance . Resistance to eritromycine, cloramfenicol, tetracycline, cotrimoxazol and levofloxacine was 38.8%; 9.7%; 20.4%; 25.2% and 2.9% respectively, increasing to values of 66.6%; 30.3%; 48.5%; 72.7% and 9.1% in the 33 penicillin resistant strains . Resistance to cefotaxime and cefepime was 9.7% and 10.6% respectively . CONCLUSIONS . A high percentage of strains of Streptococcus pneumoniae show some degree of resistance to penicillin, but with lower figures than in other studies carried out at a national level . Similarly, it was demonstrated that resistance to penicillin is significantly associated (p < 0.001) with resistance to all the antimicrobials studied, except for levofloxacine . The resistances to cefotaxime and cefepime were comparable, with less activity being observed in these when facing penicillin resistant strains of Streptococcus pneumoniae.

Infez Med, 1999, 7(2), 113 - 118
{Complicated purulent meningitis as first manifestation of a hidden HIV disease}; Manfredi R et al.; A case report of severe Streptococcus pneumoniae meningitis, prompting the diagnosis of a concurrent occult HIV infection, is presented . Despite a favorable in vitro susceptibility profile of the isolated microbial strain and timely antibiotic treatment, our patient suffered from permanent neurogical sequelae (severe bilateral central hypacusia) . The role of penumococcal complications in the context of HIV disease and AIDS is rewieved in light of recent finding reported in the literature.

Diabetes Res Clin Pract, 2003 Jun, 60(3), 213 - 6
Successful treatment of necrotizing fasciitis associated with diabetic nephropathy; Ogawa D et al.; A 50-year-old woman with a 15-year history of type 2 diabetes mellitus was admitted to our hospital due to high fever and a skin lesion with severe pain, swelling and a sensation of heat in the right thigh . Laboratory examination showed elevated C-reactive protein (CRP), thrombocytopenia, nephrotic syndrome and renal dysfunction . Her blood glucose level had been well controlled . Streptococcus agalactiae was detected in both the skin lesion and blood culture, and pathological examination revealed neutrophil infiltration in the fascia and muscle layer . The patient was diagnosed with necrotizing fasciitis, septic shock and disseminated intravascular coagulation . A combination therapy of antibiotics and surgical debridement resulted in the improvement of symptoms as supported by laboratory findings, and the skin lesion also showed improvement . Although group A streptococcus is well known to be implicated in the pathogenesis of necrotizing fasciitis, only S . agalactiae, belonging to group B streptococcus, was isolated from the tissue and blood cultures in this case . Although this organism is not virulent and rarely causes a necrotizing fasciitis, both the superficial fascial layer and underlying muscle were affected in this case . There have been only a few reports of necrotizing fasciitis due to S . agalactiae in patients with diabetes mellitus . Although the blood glucose level was well controlled in our patient, this disease might be caused by other factors, including diminished sense of touch and pain, abnormality of microcirculation and hypogammaglobulinemia due to nephrotic syndrome.

FEMS Microbiol Lett, 2003 May 16, 222(1), 69 - 74
CNE, a collagen-binding protein of Streptococcus equi; Lannergard J et al.; Streptococcus equi subspecies equi is an important horse pathogenic bacterium causing a serious disease called strangles . Using bioinformatics we identified a gene denoted cne (gene encoding collagen-binding protein from S . equi) coding for a novel potential virulence factor of this species called protein CNE . The protein is composed of 657 amino acids and has the typical features found in cell surface-anchored proteins in Gram-positive bacteria . CNE displays amino acid sequence similarities to the previously well-studied collagen-binding protein CNA from Staphylococcus aureus, a proven virulence factor in septic arthritis . Based on similarity to CNA the structure of the mature CNE protein can be divided into an N-terminal A domain and a C-terminal B domain . The highest similarity between CNA and CNE is found in the A domains . The A domain in CNA is known to be the collagen-binding domain . Two parts of cne were amplified using polymerase chain reaction (PCR) and ligated into an expression vector, and recombinant CNE proteins were produced in Escherichia coli . The purified CNE proteins were shown to display collagen-binding activity in a Western ligand blot and to inhibit collagen binding to cells of subsp . equi and to CNE-coated microtitre wells . Furthermore, the A domain of CNE was sufficient for binding collagen, and was shown to compete for the same site on collagen as CNA in inhibition studies . Using PCR, the cne gene was detected in all studied strains of subsp . equi and S . equi subsp . zooepidemicus.

J Pediatr, 2003 May, 142(5), 492 - 7
Intrapartum antibiotics and neonatal invasive infections caused by organisms other than group B streptococcus; Sinha A et al.; OBJECTIVES/STUDY DESIGN: Administration of group B streptococcal (GBS) antibiotic prophylaxis to women in labor has dramatically reduced the incidence of GBS neonatal disease, but there is little information on its impact on neonatal infections caused by other organisms . We conducted a nested case-control study to define the association between maternal intrapartum antibiotics and risk of neonatal non-GBS infection . RESULTS: In our study population, 114 of 13,224 infants had 115 non-GBS infections . The incidence of non-GBS neonatal infections fell during the study period, ranging from an attack rate of 9.6 per 1000 infants in 1990 to 1992 to 8.0 per 1000 infants in 1996 to 1998, although this trend was not statistically significant (P >.05) . The unadjusted association between neonatal infection and GBS prophylaxis was 0.89 (95% CI, 0.29, 2.6) and between neonatal infection and maternal intrapartum antibiotic due to any cause was 1.3 (95% CI, 0.65, 2.8) . CONCLUSIONS: The current policy of GBS maternal prophylaxis does not appear to convey excess risk of non-GBS infection to neonates.

Presse Med, 2003 Apr 5, 32(13 Pt 2), S17 - 20
{Contribution of linezolid to the treatment of complicated infections of the skin and soft tissues}; Gauzit R; THREE GROUPS OF INCREASING SEVERITY: According to the 2000 consensus conference, bacterial infections of the skin and soft tissues can be classified in three categories of increasing severity: bacterial dermo-hypodermal infections, bacterial dermo-hypodermal necrotizing infections, necrotizing fasciitis . The last two categories are medicosurgical emergency conditions requiring repeated surgical debridement and probabilistic antibiotic therapy . LINEZOLID: The clinical efficacy of linezolid in bacterial infections of the skin and soft tissues is comparable to that of oxacillin/dicloxacillin . Several arguments (frequent implication of Streptococcus pyogenes and Staphylococcus aureus, well-adapted spectrum, changing resistance pattern of Gram-positive cocci, efficacy against associated bacteriemia, favorable kinetics and diffusion data in cutaneous tissues) argue in favor of the use of linezolid in infections of the skin and soft tissues

Presse Med, 2003 Apr 5, 32(13 Pt 2), S5 - 8
{Epidemiology of Gram-positive infections in France: changing resistance}; Lepape A; CONTRIBUTION OF CLINICAL EPIDEMIOLOGY: Clinical epidemiology goes beyond simply counting cases of resistance . The goal is to collect clinical data contributing to an explication of epidemiological observations enabling a classification into 4 types of resistance . GRAM POSITIVE BACTERIA: Depending on the specialty, Gram positive bacteria are the cause of a variable percentage of clinical infections . In oncology and hematology, Gram-positive infections appear to be on the rise due to the increase in the number of coagulase-negative staphylococcal infections . The percentage appears to be unchanged in intensive care . Community-acquired streptococcal infections include a growing number caused by Streptococcus viridans, with the development of resistance and an aggravation of Streptococcus pneumoniae resistance . Nosocomial Gram-positive infections show that the increase in the number of meticillin-resistant Staphylococcus aureus infections is slowing down with the emergence of exceptional Staphylococcus aureus strains exhibiting intermediary resistance to glycopeptides . STREPTOCOCCUS VIRIDANS: Isolation of Streptococcus viridans is becoming increasingly frequent, particularly in immunodepressed patients or in patients with surgical conditions such as peritonitis . Several risk factors have been identified . In vitro glycopeptides and linezolide would have 100% activity against S . viridans . METICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (MRSA): Infections caused by MRSA strains are rather exceptional compared with simple colonization . All patients with suspected Staphylococcus aureus infections should not be treated as if they had a MRSA infection . STREPTOCOCCUS PNEUMONIA: Beta-lactame resistant pneumococci have shown some progression.

Infez Med, 2002 Dec, 10(4), 213 - 9
{Pharyngotonsillitis caused by Streptococcus pyogenes: clinical and epidemiological aspects and resistance phenotypes towards macrolides}; Crotti D et al.; During 2001 we analyzed 1730 pharyngeal swabs for S . pyogenes (SGA): 1142 children (0-10 years old), 132 adolescent subjects (11-17 years old), and 456 adults (18 or more years old) . 994 subjects (664 children, 85 adolescent ones, 245 adults) had acute pharyngotonsillitis . In this last group we observed 321 positivities (32.3 %) for SGA: 40.4 % among children, 24.7 % among adolescent people, 13.1 % among adults . The pharyngotonsillitis prevailed during winter and spring . The resistances (R) towards erythromycin were 27.7 % (89 cases), and among children 30.6 % (82 cases), towards clyndamicin 15.3 % (49 cases, and 17.2 %, 46 cases, among children), towards rokytamicin 11.8 % (38 cases, and 13.1 %, 35 cases, among children) . These were the phenotypes of R to erythromycin: 25.8 % M-phenotype, 19.1 % inducible (iMLS), 55.1 % constitutive (cMLS); among children respectively 25.6 %, 18.3 % and 53.7 % . Increased resistances towards 16-C macrolides, increased resistances of cMLS to erythromycin, and the persistence of R to 14-C macrolides around 30 % are discussed.

Respirology, 2003 Jun, 8(2), 208 - 12
Prevalence and clinical significance of community-acquired penicillin-resistant pneumococcal pneumonia in Thailand; Sangthawan P et al.; OBJECTIVE: The study aimed to evaluate the prevalence, clinical significance and outcome of community-acquired penicillin-resistant Streptococcus pneumoniae (PRSP) pneumonia in Thailand . METHODOLOGY: We conducted a prospective study in culture-proven pneumococcal pneumonia . Pneumococci were defined as susceptible, intermediate resistance and high resistance according to the definitions of the United States National Committee for Clinical Laboratory Standards (NCCLS) . RESULTS: Forty-six consecutive patients were enrolled . Of the S . pneumoniae isolates collected, 41.3% were resistant to penicillin (37% intermediate resistance and 4.3% high resistance) . Resistance to other antibiotics was 13% to ceftriaxone (8.7% intermediate resistance and 4.3% high resistance), 34.8% to erythromycin, 39.1% to tetracycline, 26.1% to chloramphenicol, and 43.5% to trimethoprim -sulfamethoxazole . Prior antibiotic use within 3 months was significantly associated with resistance to penicillin . The overall mortality of pneumococcal pneumonia was 26.1% . Multilobar involvement and requirement for mechanical ventilation proved to be associated with mortality . However, resistance to penicillin or ceftriaxone was not associated with death . CONCLUSIONS: According to the US NCCLS guidelines, we found a high prevalence of drug-resistant S . pneumoniae in Thai patients with community-acquired pneumonia . Prior antibiotic use was significantly associated with penicillin resistance . However, the outcome was not related to in vitro penicillin susceptibility of S . pneumoniae isolated from the patients.

Oral Microbiol Immunol, 2003 Jun, 18(3), 156 - 9
PCR method is essential for detecting Mycobacterium tuberculosis in oral cavity samples; Eguchi J et al.; Tuberculosis is a re-emerging infectious disease, and infection by Mycobacterium tuberculosis has been increasing in immunocompromised hosts, including elderly persons . M . tuberculosis-infected persons may receive dental treatment . To evaluate the risk of M . tuberculosis infection in dental clinics, we examined the detection rates of M . tuberculosis in sample of mixed saliva, dental plaque, extracted teeth, caries lesions, and denture plaque by nested polymerase chain reaction (PCR) . The detection rates by PCR in samples from mixed saliva, dental plaque, caries lesions and denture plaque obtained from tuberculosis patients were 98.0%, 92.0%, 89.0%, and 100%, respectively . The detection rates by the culture method were 17.3%, 2.0%, 0%, and 0%, respectively . M . tuberculosis also was detected from the nontuberculous mycobacteria-infected group . Strains of Actinomyces naeslundii, Porphyromonas gingivalis, and Fusobacterium nucleatum inhibited the growth of clinical strains of M . tuberculosis, but strains of Streptococcus mutans, Streptococcus sanguinis, and Actinobacillus actinomycetemcomitans did not . The present study concludes that the PCR method is essential for detecting M . tuberculosis in oral samples.

Immunol Cell Biol, 2003 Jun, 81(3), 192 - 5
FcgammaRIIA polymorphisms in Streptococcus pneumoniae infection; Yuan FF et al.; Invasive pneumococcal disease continues to be a major cause of morbidity and mortality among children and adults worldwide . Effective host defence against Streptococcus pneumoniae depends on immunoglobulin G-mediated phagocytosis of the bacteria and it has been shown in vitro that the FcgammaRIIA polymorphism (FcgammaRIIA-R131 vs FcgammaRIIA-H131) determines the capacity of immunoglobulin G2-mediated phagocytosis via this receptor . In this study, we evaluated FcgammaRIIA polymorphisms in children with pneumococcal sepsis and a number of control groups in order to investigate a possible association of FcgammaRIIA genotypes with Streptococcus pneumoniae infection . The distribution of the genotypes differed in these populations . The frequency of homozygosity for FcgammaRIIA-R/R131 in the patients was significantly higher than that in the healthy random donor population (43%vs 21%, P < 0.05) . The frequencies of FcgammaRIIA-H/H131 were similar among all groups of individuals, while the incidence of the heterozygous FcgammaRIIA-R/H131 was lower (35%vs 52%, P < 0.05) . Thus, it appears that the FcgammaRIIA-H131 polymorphic form, even in the heterozygous form, may be protective for pneumococcal sepsis and children with FcgammaRIIA-R/R131 genotype could be more at risk of infection with invasive Streptococcus pneu-moniae.

Eur J Biochem, 2003 May, 270(10), 2157 - 62
A unique variant of streptococcal group O-antigen (C-polysaccharide) that lacks phosphocholine; Bergstrom N et al.; Streptococcus mitis strain SK598, which represents a subgroup of biovar 1, possesses a unique variant of the C-polysaccharide found in the cell wall of all strains of Streptococcus pneumoniae and in some strains of S . mitis . This new variant lacks the choline methyl groups in contrast to the previously characterized forms of C-polysaccharide, which all contain one or two choline residues per repeat . The following structure of the repeating unit of the SK598 polysaccharide was established: where AAT is 2-acetamido-4-amino-2,4,6-trideoxy-d-galactose . This structure is identical to the double choline-substituted form of C-polysaccharide, except that it is substituted with ethanolamine instead of choline . This extends the number of recognized C-polysaccharide variants to four.

Birth, 2003 Jun, 30(2), 116 - 23
Taking antenatal group B Streptococcus seriously: women's experiences of screening and perceptions of risk; Darbyshire P et al.; BACKGROUND: Early-onset group B streptococcal disease is a serious cause of neonatal morbidity and mortality . Although screening protocols for group B streptococcus are common, little is known of women's perceptions of this screening and the disease itself . The purpose of this study was to gain an understanding of women's experiences, knowledge, and perceptions about this bacteria and its screening . METHODS: Nine focus group interviews with 35 women explored their experiences and understanding of group B streptococcus screening . Transcribed interview data were interpreted to identify and articulate the women's experiences . RESULTS: Most women had little knowledge or understanding of group B streptococcus, obtaining their information largely from the stories or experiences of friends or family . Women struggled to understand the meaning and implications, both physical and "moral," of the disease for their baby and for themselves, clearly indicating both the subjective and statistical importance of the concept of risk for pregnant women . CONCLUSIONS: Group B streptococcus continues to be poorly understood by pregnant women who try to understand and weigh up its risks and implications so as to make the best decisions about screening . The women participated in screening ultimately, however, since it was seen to be patently "best for baby," relatively easy for them to undergo, and part of routine antenatal care.

J Infect Dis, 2003 Jun 1, 187(11), 1694 - 703 Epub 2003 May 15.
Contribution of protein G-related alpha2-macroglobulin-binding protein to bacterial virulence in a mouse skin model of group A streptococcal infection; Toppel AW et al.; Protein G-related alpha(2)-macroglobulin-binding (GRAB) protein is a cell wall-attached determinant of group A streptococcus (GAS) that interacts with the human protease inhibitor alpha(2)-macroglobulin (alpha(2)-M) . Of 86 clinical isolates tested, 23% could bind alpha(2)-M . However, all strains tested contained the grab gene . High levels of anti-GRAB antibodies were found in the serum of convalescent GAS-infected patients, a finding that indicates that this protein is expressed during the infection process . Among the alpha(2)-M-binding strains, 80% were skin isolates, and 20% were throat isolates, findings that suggest that the skin environment is a preferential site for expression of alpha(2)-M-binding activity . To test this possibility, we determined the role of GRAB in a mouse model of GAS skin infection . The wild-type strain KTL3, which interacts with alpha(2)-M, showed high virulence . The isogenic mutant of KTL3, MR4, devoid of surface-bound GRAB, was attenuated in virulence, compared with the wild-type strain . Thus, mice infected with MR4 survived longer, developed smaller skin lesions, and exhibited lower levels of bacterial dissemination than did those infected with KTL3 . These results emphasize the role of GRAB as a virulence factor of GAS.

J Infect Dis, 2003 Jun 1, 187(11), 1686 - 93 Epub 2003 May 12.
Role of leukocyte immunoglobuin G receptors in vaccine-induced immunity to Streptococcus pneumoniae; Saeland E et al.; Members of the leukocyte immunoglobulin (Ig) G receptor (FcgammaR) family play a key role in antibody-mediated phagocytosis and can either enhance antigen presentation or down-modulate immune responses . We studied immune responses to a pneumococcal conjugate (pneumococcal polysaccharide serotype 1 {PPS1}-tetanus toxoid) and antibody-mediated protection in mice deficient for individual FcgammaRs and complement receptor 3 (CR3) . FcR gamma chain-deficient (FcR gamma chain(-/-)) mice, which lack expression of both FcgammaRI and III, had significantly lower anti-PPS1 IgG2b and IgG3 responses than did wild-type mice, whereas FcgammaRII-deficient (FcgammaRII(-/-)) mice had significantly higher IgG2a and IgG3 titers . Wild-type and FcgammaRII(-/-) mice were protected against infection with pneumococcal serotype 1, whereas immunized FcR gamma chain(-/-) and FcgammaRIII-deficient mice were not . Immunized CR3-deficient mice were protected against disease, and complement depletion had little effect on protection . These data indicate that activatory leukocyte FcgammaR, but not FcgammaRII (a murine homologue of human FcgammaRIIb), contributes to IgG-mediated protection against pneumococcal disease.

J Mol Model (Online), 2003 Jun, 9(3), 153 - 8 Epub 2003 May 15.
Structural analysis of the functional influence of the surface peptide Gtf-P1 on Streptococcus mutans glucosyltransferase C activity; Chia JS et al.; Glucosyltransferases (GtfB/C/D) in Streptococcus mutans are responsible for synthesizing water-insoluble and water-soluble glucans from sucrose and play very crucial roles in the formation of dental plaque . A monoclonal antibody against a 19-mer peptide fragment named Gtf-P1 was found in GtfC to reduce the enzyme activity to 50% . However, a similar experiment suggested almost unchanged activity in GtfD, despite of the very high sequence homology between the two enzymes . No further details are yet available to elucidate the biochemical mechanism responsible for such discrimination . For a better understanding of the catalytic behavior of these glucosyltransferases, structural and functional analyses were performed . First, the exact epitope was identified to specify the residue(s) required for monoclonal antibody recognition . The results suggest that the discrimination is determined solely by single residue substitution . Second, based on a combined sequence and secondary structure alignment against known crystal structure of segments from closely related proteins, a three-dimensional homology model for GtfC was built . Structural analysis for the region communicating between Gtf-P1 and the catalytic triad revealed the possibility for an "en bloc" movement of hydrophobic residues, which may transduce the functional influence on enzyme activity from the surface of molecule into the proximity of the active site . Figure Side chain interactions between Gtf-P1 and catalytic Asp-477 in GtfC . Calpha-tracing of GtfC with the two crucial peptides (Gtf-P1, orange; Gtf-P2, blue) and the catalytic triad residues ( red) highlighted to show their relative spatial organization . Side chains for the residues are also depicted according to their atom types . The structure is viewed with the barrel opening facing down

Rev Esp Quimioter, 2003 Mar, 16(1), 61 - 4
{Susceptibility of Streptococcus pyogenes to macrolides and quinolones in Guadalajara, Spain}; Rodriguez-Zurita ME et al.; We carried out a retrospective study of the susceptibility of 104 Streptococcus pyogenes strains, which were isolated in 2000 and 2001 from clinical samples of different origins, to penicillin, erythromycin, clindamycin, ofloxacin and levofloxacin . The susceptibility testing was performed using the agar difusion method according to the guidelines of the NCCLS . All of the isolates showed susceptibility to penicillin and clindamycin . However, we detected 11 strains that were resistant to erythromycin (10.6%) and 4 strains resistant to ofloxacin (3.8%) . We studied the resistance phenotypes of macrolides and lincosamides using erythromycin and clindamycin discs . Nine of the eleven strains that were resistant to erythromycin showed an M phenotype, while the remaining two showed inducible resistance to clindamycin, thus suggesting an MLS(B) inducible phenotype . No strains with constitutive resistance to erythromycin or clindamycin (MLS(B) constitutive phenotype) were identified . While penicillin is still uniformly active against S . pyogenes, in Guadalajara, there are 10.6% strains that are resistant to 14- and 15-atoms macrolides.

Rev Esp Quimioter, 2003 Mar, 16(1), 58 - 60
{Susceptibility of Streptococcus pyogenes isolates from pharyngeal exudates in Cordoba (Spain)}; Gordillo RM et al.; Streptococcus pyogenes is an important human pathogen . Betalactams are still the drug of choice for the treatment of infections caused by this microorganism . In recent years an increase in the use of macrolides for initial treatment in respiratory infections has been observed; consequently, the number of macrolide-resistant isolates has also increased . We investigated the susceptibility of S . pyogenes to penicillin, erythromycin, clarithromycin and clindamycin in Cordoba during 2000, 2001 and the first 6 months of 2002 . We obtained 100 isolates of S . pyogenes from 1232 pharyngeal exudates, all of which were susceptible to penicillin and 39 of which were resistant to erythromycin and clarithromycin . Twenty-six of these 39 isolates were susceptible to clindamycin.

Arch Oral Biol, 2003 Jun, 48(6), 431 - 8
Acid diffusion through extracellular polysaccharides produced by various mutants of Streptococcus mutans; Hata S et al.; Mutants of Streptococcus mutans V403, constructed by allelic exchange and altered in their capacity to produce enzymes involved in the production of extracellular polysaccharides from sucrose, were used to study the role of glucans and fructans in the diffusion of ions through cell concentrates . A 4.0mm diameter, 0.75 mm deep diffusion chamber with an ion-sensitive field-effect transistor electrode positioned at the base was used to monitor the diffusion of hydronium ions from a sodium lactate buffer using cell concentrates prepared from bacteria grown in various concentrations of sucrose and glucose . The wild-type strain V403 produced at least seven times as much water-insoluble glucan (ISG) from sucrose as mutants deficient in various combinations of glucosyltransferase B (GTF B), GTF C, GTF D and fructosyltransferase . The fastest diffusion of hydronium ions occurred with sucrose-grown cell concentrates of strain V403, and the time of diffusion to the bottom of the chamber was approximately 2.3 times longer when this strain was grown in glucose . The speed of diffusion with glucose-grown V403 was similar to that obtained with each of the mutants . When cells of strain V403 grown in sucrose and glucose were mixed, increases in diffusion speed were found to be directly related to the proportion of sucrose-grown cells . The mixing of ISG with several strains of S . mutans revealed that increases in diffusion speed were directly related to the quantity of ISG added.

Crit Rev Biochem Mol Biol, 2003, 38(2), 143 - 68
Analysis of structure and function of putative surface-exposed proteins encoded in the Streptococcus pneumoniae genome: a bioinformatics-based approach to vaccine and drug design; Rigden DJ et al.; Streptococcus pneumoniae is the most common cause of fatal community-acquired pneumonia, middle ear infection, and meningitis . The prevention and treatment of this infection have become a top priority for the medical-scientific community . The present polysaccharide-based vaccine used to immunize susceptible hosts is only approximately 60% effective and is ineffective in children younger than 2 years of age . The new conjugate vaccine, based on the engineered diphtheria toxin coupled to polysaccharide antigens . is approved only for use in children under 2 years of age to treat invasive disease . While penicillin is the drug of choice to treat infections secondary to S . pneumoniae, increasing numbers of bacterial strains are resistant to penicillin as well as to broad spectrum antibiotics such as vancomycin . Thus, there is a need to identify new strategies to prevent and treat diseases caused by to S . pneumoniae . In this article, we summarize the utilization of the recently available S . pneumoniae genomic information in order to identify and characterize novel proteins likely located on the surface of this Gram-positive pathogenic bacterium . Because only a limited number of surface proteins of S . pneumoniae have been characterized to date, this information provides new insights into the pathogenesis of this organism as well as highlights possible avenues for its treatment and/or prevention in the future . The review is divided into two sections . First, we brietly summarize current information about known surface-exposed proteins of S . pneumoniae . This is followed by the illustration of procedures for the identification of new putative surface-exposed proteins . These have signal peptides required for their extra-cytoplasmic transport and/or additional signature sequences . Some of these will be S . pneumoniae virulence factors . The signature sequences we have chosen are those leading to protein binding to choline present on the bacterial surface, attachment to peptidoglycan of the cell wall, or anchoring to lipids of the cytoplasmic membrane . All these signatures are indicative of binding of proteins to the surface of this organism . Secondly, we illustrate the application of bioinformatics and modeling tools to these selected proteins in order to provide information about their likely functions and preliminary three-dimensional structure models . The focal point of the analysis of these proteins, their sequences, and structures is the evaluation of their antigenic properties and possible roles in pathogenicity . The information obtained from the genome analysis will be instrumental in the development of a more effective prophylactic and/or therapeutic agents to prevent and to treat infections due to S . pneumoniae.

Pediatr Crit Care Med, 2003 Apr, 4(2), 170 - 5
Elevated cerebrospinal fluid levels of glutamate in children with bacterial meningitis as a predictor of the development of seizures or other adverse outcomes; Ma W et al.; OBJECTIVE: Evaluation of elevated cerebrospinal fluid levels of glutamate in children with bacterial meningitis as a predictor of seizures or other adverse outcomes . DESIGN: Prospective cohort study with controls . SETTING: A 36-bed pediatric intensive care unit and primary pediatric referral center . PATIENTS: From 1999 to 2001, a total of 55 patients, between the ages of 0 and 18 yrs, with lumbar punctures performed for suspected meningitis . MEASUREMENTS AND MAIN RESULTS: A total of 23 patients had bacterial meningitis confirmed by cerebrospinal fluid/blood culture and elevated cerebrospinal fluid white blood cell counts, and 32 patients, who tested negative, were included as controls . The median age for the patients with meningitis was 1.0 yr (range, 0.0-15.2 yrs), and in the culture-negative group (control group), the median age was 0.3 yrs (range, 0.0-17.0 yrs) . The average cerebrospinal fluid white blood cell count was 2707 +/- 3897 in the group with bacterial infection, whereas in the control group, the average was 148 +/- 259 (p < .01) . Patients with bacterial meningitis had a mean cerebrospinal fluid glutamate level of 60.5 +/- 88.4 mol/L, whereas the mean cerebrospinal fluid glutamate level in the control group was 4.9 +/- 11.0 mol/L (p < .01) . However, only 10 of 23 children with bacterial meningitis had a second lumbar puncture performed during the study . There was no correlation between the cerebrospinal fluid white blood cell count and cerebrospinal fluid glutamate levels in either the study or control patients . None of the control patients developed seizures or neurologic deficits, despite some patients having elevated glutamate levels . However, four patients with bacterial meningitis developed seizures after admission to the hospital, and ten were discharged with at least some neurologic sequelae attributable to their infection . Two out of the three who developed seizures and had a repeat lumbar puncture demonstrated persistent elevation of cerebrospinal fluid glutamate levels . In addition, 70% of patients (7 of 10) with Streptococcus pneumoniae meningitis developed neurologic complications (p = .04) . CONCLUSIONS: Bacterial meningitis in children causes an increase in cerebrospinal fluid glutamate that in many cases persists over time . However, in this limited study, neither higher nor persistent elevation of cerebrospinal fluid glutamate levels is predictive of which patients might develop seizures or other apparent immediate adverse outcomes after invasive infection . The responsible organism seems to have far more significance in predicting the development of adverse sequelae.

Proteomics, 2003 May, 3(5), 627 - 46
Cellular and extracellular proteome analysis of Streptococcus mutans grown in a chemostat; Len AC et al.; The oral pathogen, Streptococcus mutans, was grown under glucose limitation in a chemostat at pH 7.0 and a dilution rate of 0.1 h(-1) to mimic the conditions prevailing in a healthy human oral cavity in between meal times . Solubilized cellular and extracellular proteins were separated by two-dimensional gel electrophoresis (2-DE) and, following tryptic digestion, 421 protein spots analyzed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry or electrospray ionization-tandem mass spectrometry . Analyses of the mass spectral data showed that the proteins matched the translation products of 200 different open reading frames (ORFs) deduced from contigs of the S . mutans UA159 genome and thus represented proteins derived from approximately 11% of the total ORFs of the bacterium . Of the identified proteins, 172 (including one surface protein) were characterized in the cellular fraction, and the remaining 28 (including two surface proteins) were uniquely identified from the culture fluid . The expression and therefore the existence of 30 proteins previously designated as 'hypothetical' or with no known function was confirmed . 2-DE of whole cell lysates revealed only a single intrinsic membrane protein . This is consistent with proteomic analyses of other Gram-positive bacteria where hydrophilic proteins represent the vast majority of those characterized.

J Antimicrob Chemother, 2003 Jun, 51(6), 1431 - 4 Epub 2003 May 13.
Intrapulmonary penetration of linezolid; Honeybourne D et al.; OBJECTIVE: This study was designed to measure the concentrations of linezolid in bronchial mucosa, pulmonary macrophages and epithelial lining fluid and to compare them with simultaneous blood levels . METHODS: Ten adult patients undergoing bronchoscopy for diagnostic purposes were given oral linezolid at a dosage of 600 mg twice a day for a total of six doses . Patients with active lung infection were excluded from the study . Flexible bronchoscopy was carried out between 2 and 8 h after the last dose of linezolid . Bronchial biopsies and bronchoalveolar lavage were carried out and a simultaneous blood sample obtained . Linezolid levels were measured using high-performance liquid chromatography (HPLC) . RESULTS: Mean concentrations of linezolid were 13.4 mg/L in serum, 10.7 mg/kg in mucosa, 8.1 mg/L in alveolar macrophages and 25.1 mg/L in epithelial lining fluid . The mean site/serum concentration ratios were 0.79 for bronchial mucosa, 0.71 for macrophages and 8.35 for epithelial lining fluid . CONCLUSIONS: The MIC90 (< or =4 mg/L) of linezolid for Staphylococcus aureus and Streptococcus pneumoniae was exceeded in serum and bronchial mucosa in all subjects, in epithelial lining fluid in nine subjects and in macrophages in six subjects.

Surg Infect (Larchmt), 2003 Spring, 4(1), 29 - 35
Pathogenesis of posttraumatic empyema: the impact of pneumonia on pleural space infections; Hoth JJ et al.; BACKGROUND: Thoracic empyema may result either from primary pneumonic sources or intraabdominal sources of infection that seed the pleural space secondarily . In patients with thoracostomy tubes, empyema may result when blood in the pleural space becomes contaminated during tube insertion . To elucidate the cause of posttraumatic empyema, preoperative bronchoalveolar lavage (BAL)/sputum cultures obtained from patients with posttraumatic empyema were compared with cultures obtained at the time of decortication . MATERIALS AND METHODS: A retrospective study was conducted of trauma patients who developed empyema and underwent either video-assisted thoracoscopy or thoracotomy with decortication following blunt or penetrating trauma . At our level I trauma center, we studied all empyema cases diagnosed from November, 1998 to July, 2001 . Data collection included patient demographics, injuries sustained, preoperative BAL/sputum cultures, and culture data obtained at the time of decortication . All BAL/sputum cultures were performed no more than 5 days prior to decortication . RESULTS: Thirty-seven patients (26 blunt/11 penetrating) were identified . No patients had concurrent intra-abdominal sources of infection . All patients had at least one chest tube placed prior to decortication . Preoperative respiratory cultures (BAL/sputum) were obtained in 34 patients . The most common organisms isolated were Staphylococcus aureus in six patients (18%) and Hemophilus influenzae in six patients (18%) . Intraoperative cultures were obtained in all 37 patients, with the most common organism being S . aureus isolated in 22 patients (60%) . Interestingly, a correlation between preoperative BAL/sputum and intraoperative cultures was found in only seven of the 34 patients (21%) who had concomitant respiratory and pleural cultures . Cultures positive for S . aureus were isolated from five patients, Streptococcus pneumoniae from one patient, and Pseudomonas aeruginosa from one patient . CONCLUSION: Little correlation existed between preoperative BAL/sputum cultures and intraoperative cultures in this series of patients with posttraumatic empyema . This suggests that the causation is most often not a parapneumonic process . Furthermore, since S . aureus was the most common organism recovered from empyema, the source was more likely from inoculation of the pleural space by the injury itself or by tube thoracostomy.

West Afr J Med, 2002 Jul-Sep, 21(3), 233 - 6
Nasopharyngeal carriage and susceptibility patterns of Streptococcus pneumoniae in Kumasi, Ghana; Denno DM et al.; Penicillin resistant Streptococcus pneunmoniae poses an increasing problem in paediatrics, particularly in less developed countries . Outside of South Africa, little is known about S . pneumoniae susceptibilities in Sub-Saharan Africa . The objective of this study was to determine the prevalence of pneumococcal colonization and antimicrobial susceptibility among children in urban Ghana . METHODS: Nasopharyngeal pneumococcal colonization was examined in 311 children attending a polyclinic for sick children and an immunization clinic in Kumasi, Ghana . Isolates were tested for antibiotic susceptibility to penicillin, tetracycline, erythromycin, chloramphenicol, cefuroxime, cefotaxime, ceftriaxone, and trimethoprim-sulfamethoxazole . RESULTS: Over half (51.4%) of subjects were colonized with S . pneumoniae and 17% of isolates were resistant to penicillin, all demonstrating intermediate resistance . S . pneumoniae strains were also frequently resistant to trimethoprim-sulfamethoxazole and tetracycline, less so to chloramphenicol and cefuroxime and were almost uniformly sensitive to cefotaxime, cefriaxone and erythromycin . CONCLUSIONS: Our study shows a high rate of pneumococcal nasopharyngeal colonization and a concerning level of penicillin resistance although at a less alarming rate than seen in some other countries . Multiple antimicrobial resistance was also noted especially among drugs readily available and commonly used . These data impact treatment choices in pneumococcal disease . Vaccine may play an important role in disease limitation . An effort to curtail the misuse of antibiotics, by prescription and otherwise, may prevent further increases in resistance rates.

Brain Pathol, 2003 Apr, 13(2), 123 - 32
Morphological correlates of acute and permanent hearing loss during experimental pneumococcal meningitis; Klein M et al.; In patients with acute bacterial meningitis, hearing loss can be transient but is often permanent . The mechanisms underlying meningitis-associated hearing loss are not fully understood . Therefore, we investigated the morphological correlates of hearing loss in a rat model of pneumococcal meningitis . Transcutaneous intracisternal injection of Streptococcus pneumoniae resulted in a dose-dependent hearing loss (determined by auditory brainstem response audiometry), which was partially reversible during the acute stage . Nevertheless, a severe permanent hearing loss persisted until 2 weeks after infection . Suppurative labyrinthitis was accompanied by blood-labyrinth barrier disruption (determined by cochlear Evans blue extravasation), which correlated closely with hearing loss during the acute stage but not after recovery . Two weeks after infection, spiral ganglion neuronal density was markedly decreased and correlated with the severity of permanent hearing loss . Neuronal loss can be explained by the new finding of meningitis-associated spiral ganglion neuronal necrosis rather than apoptosis (determined by morphology, TUNEL staining, and immunohistochemistry).

J Neuroimmunol, 2003 May, 138(1-2), 31 - 7
Interleukin-18 gene-deficient mice show enhanced defense and reduced inflammation during pneumococcal meningitis; Zwijnenburg PJ et al.; To determine the role of endogenous interleukin-18 (IL-18) in pneumococcal meningitis, meningitis was induced in IL-18 gene-deficient (IL-18(-/-)) and wild-type (WT) mice by intranasal inoculation of Streptococcus pneumoniae with hyaluronidase . Induction of meningitis resulted in an upregulation of both pro- and mature IL-18 in brain tissue in WT mice . IL-18(-/-) and WT mice were equally susceptible to develop meningitis after intranasal infection, yet IL-18(-/-) mice showed a prolonged survival and a suppressed inflammatory response, as reflected by a less profound inflammatory infiltrate around the meninges and lower concentrations of cytokines and chemokines in brain tissue . These findings suggest that endogenous IL-18 contributes to a detrimental inflammatory response during pneumococcal meningitis and that elimination of IL-18 may improve the outcome of this disease.

Diagn Microbiol Infect Dis, 2003 May, 46(1), 77 - 80
Influence of patient age on the susceptibility patterns of Streptococcus pneumoniae isolates in North America (2000-2001): report from the SENTRY Antimicrobial Surveillance Program; Jones RN et al.; Risks of developing resistance in Streptococcus pneumoniae can be greatly influenced by antimicrobial use that is often dictated by patterns of prescribing at various patient ages . The results from the SENTRY Antimicrobial Surveillance Program (2000-2001; North America) were examined for differing susceptibility profiles (25 antimicrobials) indexed by five patient age groups . All MIC results were from reference methods performed in central laboratories . Pneumococcal resistance rates in the youngest patient group (0-5 years) were significantly (p < 0.05) higher for penicillin, other beta-lactams, macrolides, tetracyclines and trimethoprim/sulfamethoxazole . In contrast, fluoroquinolone resistance in S . pneumoniae was greatest in the patients >/= 65 years (1.4% resistance to gatifloxacin, levofloxacin and moxifloxacin), where use of this class has been escalating . Continued local and global surveillance of resistances in common respiratory tract pathogens such as S . pneumoniae appears to be prudent practice to guide effective chemotherapy.

Med J Aust, 2003 May 19, 178(10), 505 - 7
Pneumococcal meningitis masquerading as subarachnoid haemorrhage; Chatterjee T et al.; A 43-year-old woman taking warfarin for past venous thrombosis presented with 4 days of flu-like symptoms and deterioration in level of consciousness . Computed tomography suggested subarachnoid haemorrhage, and magnetic resonance imaging showed widespread cerebral infarcts . However, these seemed out of proportion to the amount of haemorrhage, and lumbar puncture revealed meningitis caused by Streptococcus pneumoniae.

Arch Pathol Lab Med, 2003 Jun, 127(6), 718 - 20
Comparison of direct selective versus nonselective agar media plus LIM broth enrichment for determination of group B streptococcus colonization status in pregnant women; Elsayed S et al.; CONTEXT: Group B streptococcus (GBS) is the most common cause of early-onset neonatal sepsis in developed countries, and determination of the GBS colonization status in pregnant patients near term is essential for the provision of prophylactic measures to prevent early-onset disease . OBJECTIVES: To determine if GBS recovery rates and/or result turnaround times for vaginal or combined vaginal/rectal swab specimens from pregnant patients near term are enhanced if swabs are inoculated initially onto selective versus nonselective agar media, in addition to the standard Centers for Disease Control and Prevention method . DESIGN: Prospective laboratory analysis . SETTING: Urban health region/centralized diagnostic microbiology laboratory . PATIENTS: Pregnant women presenting for routine obstetrical care and collection of vaginal or combined vaginal/rectal swab specimens for GBS testing at 35 to 37 weeks' gestation . INTERVENTION: Culture of specimens directly onto selective (5% sheep blood with colistin and nalidixic acid) or nonselective (5% sheep blood) agar media, in addition to LIM broth enrichment and terminal subculture . MAIN OUTCOME MEASURES: Group B streptococcus recovery rate and culture result turnaround time . RESULTS: A total of 639 specimens were tested, with 128 (20%) positive for GBS . Sixty-three isolates were recovered on direct agar media at 24 hours, of which 16 (12.5%) were isolated on selective plates only . An additional 38 isolates were recovered at 48 hours from direct plates . Twenty-seven (21.1%) isolates that failed to grow on direct plates were recovered from the LIM broth subculture only . Three (2.3%) isolates not recovered from LIM broths were detected at 48 hours on the direct selective (2 isolates) and nonselective (1 isolate) agar plates . A 24-hour result turnaround time was achieved for 63 (49.2%) and 47 (36.7%) of the 128 culture-positive specimens for direct selective and nonselective plates, respectively (chi2 = 76.63, P <.001) . CONCLUSIONS: Use of direct selective agar media, in addition to LIM broth enrichment, for the determination of the GBS colonization status in pregnant patients near term results in decreased turnaround time for reporting positive results.

J Microbiol Immunol Infect, 2003 Mar, 36(1), 21 - 5
Predictive value of clinical features in differentiating group A beta-hemolytic streptococcal pharyngitis in children; Lin MH et al.; Identifying children with acute pharyngitis caused by group A beta-hemolytic Streptococcus (GABHS) is an important task for pediatricians . This study examined the value of certain clinical symptoms and signs in predicting a positive culture result . A total of 442 children who presented at the outpatient department with pharyngeal erythema were enrolled . The clinical features of patients with positive throat cultures for GABHS were compared to those with negative culture results . Throat cultures were positive for GABHS in 120 (27%) patients . Patients aged between 5 and 10 years had a higher prevalence of GABHS pharyngitis . Significant differences between the groups with and without GABHS pharyngitis were noted for the presence of sore throat (p < 0.001), tonsillar swelling (p < 0.001), anterior cervical adenopathy (p = 0.004), and scarlatiniform rash (p < 0.001), but not for the presence of fever, cough, rhinorrhea, abdominal pain, headache, tonsillar exudate, or palatal petechiae . Despite these strong associations, none of these symptoms or signs had both high sensitivity and specificity, and the positive predictive values of these individual findings were never greater than 50% . The results indicate that diagnosis based on clinical grounds alone is unreliable although there are certain individual symptoms and signs that are associated with GABHS pharyngitis . These symptoms and signs may be helpful in modifying estimates of probability of infection with GABHS . Throat cultures in suspected patients remain mandatory.

J Dairy Sci, 2003 Apr, 86(4), 1233 - 9
Evaluation of the surveillance program of Streptococcus agalactiae in Danish dairy herds; Andersen HJ et al.; The aim of this study was to evaluate the Danish surveillance program of Streptococcus agalactiae in dairy herds with respect to 1) fluctuation over time of the presence of S . agalactiae in bulk tank milk, 2) sensitivity and specificity of the bacteriological method used, and 3) contamination of bulk tank milk samples with milk from other herds . From June to September 1996, bulk tank milk was sampled from 100 Danish dairy herds seven times, with intervals of 2 wk . The samples were examined for the presence of S . agalactiae by four different methods: 1) by the method approved for the program, 2) after ultrasonic treatment of the milk before examination, 3) after freezing down the milk before examination, and 4) after selective preparation of the milk . Selected strains of S . agalactiae were examined by restriction fragment length polymorphism of the gene encoding rRNA to discriminate between the isolates . Streptococcus agalactiae was found in eight of 96 herds in which S . agalactiae had never previously been found during the surveillance program . Streptococcus agalactiae was not found in all seven sampling rounds in any of the eight herds . Comparing the approved method with supplemental findings by the other methods, the estimated sensitivity was (95% confidence limits): 0.786 (0.628; 0.892) and the estimated specificity (95% confidence limits): 0.995 (0.985; 0.999) . Using all four methods on the same sample could increase the sensitivity, but by comparing the methods individually, there was no significant difference between any of them (P > 0.10) . In milk samples from three herds, the ribotype of S . agalactiae was the same as in milk from herds sampled just before; therefore, it could not be ruled out that cross-contamination could occur . Taking into account that S . agalactiae in bulk tank milk reflects the presence of S . agalactiae in at least one udder quarter, this investigation gives further reason to assume that S . agalactiae can be seen sporadically in several herds . A surveillance program based on annual bulk tank milk sample examinations will only detect a limited number of S . agalactiae infected herds . If the overall aim is to identify herds where the infection is established, annual bulk tank milk sample examinations combined with the information of number of colonies of S . agalactiae in the sample will be sufficient.

Pharmacotherapy, 2003 May, 23(5), 638 - 42
Targeting bacterial virulence: the role of protein synthesis inhibitors in severe infections . Insights from the Society of Infectious Diseases Pharmacists; Coyle EA; Society of Infectious Diseases Pharmacists; Morbidity and mortality due to certain bacterial pathogens have not declined despite the availability of effective antimicrobial treatments . Staphylococcus aureus and Streptococcus pyogenes cause a number of serious infections, such as necrotizing fasciitis and toxic shock syndrome, which are associated with the release of bacterial toxins . Animal studies have demonstrated clindamycin, a protein synthesis inhibitor, to be more effective in treating these severe infections than other more susceptible antimicrobial treatments . Linezolid, another protein synthesis inhibitor, also has shown efficacy in in vitro studies . Human trials to validate the effects of antibiotic therapies on bacterial virulence have not been performed . Future animal and human studies are needed to help elucidate the immunomodulatory mechanisms of protein synthesis inhibitors in order to optimize antimicrobial treatment and decrease the morbidity and mortality associated with severe bacterial infections.

Arch Mal Coeur Vaiss, 2003 Apr, 96(4), 300 - 4
{Infectious endocarditis . A study of 50 patients in a non-university hospital}; Cellarier G et al.; The authors report the results of a single centre study of 50 consecutive patients (average age 66 +/- 14 years; 36 men), admitted between 1992 and 2001 to a peripheral hospital for infectious endocarditis (IE) . The median interval to diagnosis was 57 days . There was an underlying cardiac disease in 52% of cases, usually valvular (42%) . The site of the IE was the mitral valve in 21 cases, the aortic valve in 19 cases, mitro-aortic valves in 5 cases, native tricuspid valves in 2 cases and pacing catheters in 4 cases (associated with valvular endocarditis in one patient) . The causal organism was usually a streptococcus (60%, including 28% of streptococcus bovis), or a staphylococcus (22%): no organism could be found in 7 patients . The average follow-up was 33 +/- 30 months: surgery was indicated in half the patients and 3 patients were turned down because of their poor general condition . In all, 34% of patients died (24% of their IE) in a median interval of 6 months, mainly from infectious or haemodynamic complications . Poor prognostic factors were: age > 70 years, "blind" antibiotic therapy, large-sized vegetations, embolism and renal failure . These data, comparable to the results observed in large series in the literature, underline the importance of multi-disciplinary management of IE and strict prophylaxis.

Nat Med, 2003 Jun, 9(6), 736 - 43 Epub 2003 May 12.
Pneumococcal vaccination decreases atherosclerotic lesion formation: molecular mimicry between Streptococcus pneumoniae and oxidized LDL; Binder CJ et al.; During the progression of atherosclerosis, autoantibodies are induced to epitopes of oxidized low-density lipoprotein (oxLDL) and active immunization of hypercholesterolemic mice with oxLDL ameliorates atherogenesis . We unexpectedly found that many autoantibodies to oxLDL derived from 'naive' atherosclerotic mice share complete genetic and structural identity with antibodies from the classic anti-phosphorylcholine B-cell clone, T15, which protect against common infectious pathogens, including pneumococci . To investigate whether in vivo exposure to pneumococci can affect atherogenesis, we immunized Ldlr(-/-) mice with Streptococcus pneumoniae . This induced high circulating levels of oxLDL-specific IgM and a persistent expansion of oxLDL-specific T15 IgM-secreting B cells primarily in the spleen, which were cross-reactive with pneumococcal determinants . Pneumococcal immunization decreased the extent of atherosclerosis, and plasma from these mice had an enhanced capacity to block the binding of oxLDL to macrophages . These studies show molecular mimicry between epitopes of oxLDL and S . pneumoniae and indicate that these immune responses can have beneficial effects.

Caries Res, 2003 May-Jun, 37(3), 212 - 7
A new selective medium for Streptococcus mutans and the distribution of S . mutans and S . sobrinus and their serotypes in dental plaque; Hirasawa M et al.; A new selective medium (MS-MUT) was developed for the isolation of Streptococcus mutans from clinical specimens . The average growth recovery of S . mutans on MS-MUT medium was 72.4% of that on MS medium . Growth of Streptococcus sobrinus was significantly inhibited on the medium with an average recovery of 0.034% . In 103 subjects, S . MUTANS was detected at 58.3, 75.0 and 95.7% in the dental plaque of caries-free (CF), caries-inactive (CI) and caries-active (CA) subjects, respectively . S . sobrinus was detected in 8.3, 13.6 and 38.3% of CF, CI and CA subjects, respectively . S . sobrinus alone was detected in only 4.3% of CA subjects . The subjects in whom neither S . mutans nor S . sobrinus were detected were 41.6% in CF and 25.0% in CI . The most predominant serotype was C with a 67% detection rate . S . sobrinus, serotypes D or G were usually found together with S . mutans .

Caries Res, 2003 May-Jun, 37(3), 190 - 3
The effect of variable energy input from a novel light source on the photoactivated bactericidal action of toluidine blue O on Streptococcus Mutans; Williams JA et al.; Although the combination of toluidine blue O (TBO) dye and laser light at a wavelength of 633 nm has a bactericidal effect, light from laboratory lasers can only be directed externally at a bacterial colony or suspension . In this study a novel delivery system guided the laser light to an 800-micrometer diameter spherical tip (an isotropic tip) from which light radiated producing a uniform sphere of light within the colony or suspension . The system was highly effective in killing TBO-treated Streptococcus mutans NCTC 10449 in stirred planktonic suspension, killing at least 10(9 )cfu/ml . Antibacterial action increased as the delivered energy dose increased . Energy doses of 1.8 J or more produced 100% kills and log reductions of 8-10 cfu/ml . Neither TBO dye nor light alone had a significant antibacterial effect under the experimental conditions used . The existence of a threshold energy, i.e . a minimum energy required before bactericidal action occurred, could not be demonstrated .

Caries Res, 2003 May-Jun, 37(3), 185 - 9
Effect of a varnish containing chlorhexidine and thymol (Cervitec) on approximal caries in 13- to 16-year-old schoolchildren in a low caries area; Haukali G et al.; BACKGROUND: Previous studies on the effect of the chlorhexidine and thymol-containing varnish (Cervitec((R))) have consistently shown a reduction in STREPTOCOCCUS MUTANS, while the data on the caries-inhibiting effect are conflicting . AIM: To measure the effect of a chlorhexidine- and thymol-containing varnish (Cervitec) on approximal caries in a low caries population . MATERIAL: Eighty-five schoolchildren, 13 years of age, entered the study after being selected on the basis of bitewing radiographs . Children with at least one approximal lesion were included after informed consent . METHODS: The study was carried out as a double-blind, randomized controlled trial according to a split-mouth design using Cervitec on one side and a placebo varnish on the other side . All approximal surfaces between molars and premolars were treated every 3rd month . After 2 years new bitewing radiographs were taken . A total of 73 children completed the 2-year study . RESULTS: Neither the difference in number of new lesions between the Cervitec-treated and the placebo-treated side (d: -0.21; 95% CI: -0.57; 0.16) nor the mean difference in number of already existing lesions that progressed (d: -0.01; 95% CI: -0.33; 0.30) were statistically significant (paired t test; p > 0.05) . CONCLUSION: The results of our study do not indicate an effect of Cervitec on initiation or progression of approximal caries in a population with a low DMFS .

Chest, 2003 May, 123(5), 1615 - 24
Community-acquired bloodstream infection in critically ill adult patients: impact of shock and inappropriate antibiotic therapy on survival; Valles J et al.; DESIGN: The objectives were to characterize the prognostic factors and evaluate the impact of inappropriate empiric antibiotic treatment and systemic response on the outcome of critically ill patients with community-acquired bloodstream infection (BSI) . PATIENTS: A prospective, multicenter, observational study was carried out in 339 patients admitted in 30 ICUs for BSI . RESULTS: Crude mortality was 41.5% . Septic shock was present in 184 patients (55%) . The pathogens most frequently associated with septic shock or death were Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae, which accounted for approximately half of the deaths . Antibiotic treatment was found to be inappropriate in 14.5% of episodes . Patients in septic shock with inappropriate treatment had a survival rate below 20% . Multivariate analysis identified a significant association between septic shock and four variables: age > or = 60 years (odds ratio {OR}, 1.96), previous corticosteroid therapy (OR, 2.58), leukopenia (OR, 2.32), and BSI secondary to intra-abdominal (OR, 2.38) and genitourinary tract (OR, 2.29) infections . The variables that independently predicted death at ICU admission were APACHE (acute physiology and chronic health evaluation) II score > or = 15 (OR, 2.42), development of septic shock (OR, 3.22), and inappropriate empiric antibiotic treatment (OR, 4.11) . This last variable was independently associated with an unknown source of sepsis (OR, 2.49) . Mortality attributable to inappropriate antibiotic treatment increased with the severity of illness at ICU admission (10.7% for APACHE II score < 15 and 41.8% for APACHE II score > or = 25, p < 0.01) . CONCLUSIONS: Inappropriate antimicrobial treatment is the most important influence on outcome in patients admitted to the ICU for community-acquired BSI, particularly in presence of septic shock or high degrees of severity . Initial broad-spectrum therapy should be prescribed to septic patients in whom the source is unknown or in those requiring vasopressors.

Clin Immunol, 2003 Apr, 107(1), 20 - 9
Effects of multidose combination chemotherapy on the humoral immune system; Zandvoort A et al.; Patients receiving multidose combination chemotherapy are at risk for severe, life-threatening infections, caused by among others encapsulated bacteria like Streptococcus pneumoniae . The splenic marginal zone is essential in the initiation of immune responses to S . pneumoniae . We analyzed effects of multidose combination chemotherapy on B-cell subpopulations . Immune response capacity was evaluated by using Pneumovax (PPS) or Tetavax (TT) as antigenic challenge . Three days after finishing therapy, all B-cell subpopulations in bone marrow and spleen were severely reduced, including the mature marginal zone B-cell population . When analyzing the anti-PPS immune response capacity at 3 days after finishing therapy, we found that the IgM antibody levels did not differ significantly from control immunized rats . The IgG antibody levels were significantly lower compared to control immunized rats but still significantly higher compared to unimmunized rats . The depletion of marginal zone B cells by multidose combination chemotherapy most likely contributes to the prolonged period that patients are at risk for developing severe infections after chemotherapy, despite the capacity to generate sufficient antibody levels . It is conceivable that the local (temporary) loss of immunological memory, together with the supposed inability to generate a humoral response in a short time frame, plays an important role in this vulnerability.

New Microbiol, 2003 Apr, 26(2), 187 - 92
Streptococcus pneumoniae nasopharyngeal colonization in young healthy children: rate of carriage, serotype distribution, and antibiotic resistance; Mosca A et al.; The nasopharyngeal colonization rate of Streptococcus pneumoniae and its antibiotic susceptibility was determined in a given population of 317 young children (ages 1-7 years) in the area of Bari, Italy . 18.29% of the cultures were positive for S . pneumoniae . 8.62% of the strains were intermediately resistant to penicillin . Erythromycin-(65.51%) and cotrimoxazole-(17.24%) resistance was also observed whereas all the strains resulted uniformely susceptible to cefotaxime and ceftriaxone . The high rate of nasopharyngeal carriage of Streptococcus pneumoniae along with the resistance to antibiotics widely used in the community suggests the importance of epidemiological surveillance as well as the application of new vaccine strategies.

Nature, 2003 May 8, 423(6936), 177 - 81
Pathogenic bacteria attach to human fibronectin through a tandem beta-zipper; Schwarz-Linek U et al.; Staphylococcus aureus and Streptococcus pyogenes, two important human pathogens, target host fibronectin (Fn) in their adhesion to and invasion of host cells . Fibronectin-binding proteins (FnBPs), anchored in the bacterial cell wall, have multiple Fn-binding repeats in an unfolded region of the protein . The bacterium-binding site in the amino-terminal domain (1-5F1) of Fn contains five sequential Fn type 1 (F1) modules . Here we show the structure of a streptococcal (S . dysgalactiae) FnBP peptide (B3) in complex with the module pair 1F12F1 . This identifies 1F1- and 2F1-binding motifs in B3 that form additional antiparallel beta-strands on sequential F1 modules-the first example of a tandem beta-zipper . Sequence analyses of larger regions of FnBPs from S . pyogenes and S . aureus reveal a repeating pattern of F1-binding motifs that match the pattern of F1 modules in 1-5F1 of Fn . In the process of Fn-mediated invasion of host cells, therefore, the bacterial proteins seem to exploit the modular structure of Fn by forming extended tandem beta-zippers . This work is a vital step forward in explaining the full mechanism of the integrin-dependent FnBP-mediated invasion of host cells.

Infez Med, 1999, 7(3), 187 - 191
{Streptococcus bovis as an opportunistic pathogen during advanced HIV disease}; Manfredi R et al.; Three rare case reports of HIV-related Streptococcus bovis bacteremia are described, and discussed on the basis of a literature review . The association with an advanced immunodeficiency, leukopenia-neutropenia, and liver cirrhosis is underlined as well as the possibility of multiple recurrences and the lack of apparent gastrointestinal lesions as risk factors.

Infez Med, 1999, 7(3), 177 - 186
{Necrotizing fasciitis: case reports and review of the literature}; Di Gregorio P et al.; Necrotizing fasciitis is a rare, rapidly progressing infection affecting the superficial fascia and the subcutaneous tissue, accompanied by severe systemic toxicity and multiorgan failure . It is caused by aerobic and anaerobic bacteria, occasionally in a synergistic polymicrobial combination (Type I Necrotizing Fasciitis); in other cases group A -haemolitic Streptoccoccus is the organism responsible for the infection (Type II Necrotizing Fasciitis) . The infection often originates from small traumatic injuries or operative wounds and rapidly spreads especially in individuals with identifiable risk factors or immunocompromised patients . Sometimes necrotizing fasciitis occurs when no known portal of entry for bacteria is present . The increasing incidence of necrotizing fasciitis observed may reflect a resurgence of highly virulent mutant strains of group A beta-haemolitic Streptococcus . The pathogenesis, clinical features and treatment of the disease have been reviewed in the light of recent literature . We also report clinical data for four patients with necrotizing fasciitis . They show the importance of early diagnosis and rapid, aggressive and radical surgical intervention . High-dose broad-spectrum antibiotic therapy and intensive medical support are also required to avoid a fatal outcome.

Chem Pharm Bull (Tokyo), 2003 May, 51(5), 494 - 8
Synthesis, characterization, and antibacterial activities of some rare Earth metal complexes of pipemidic acid; Yang L et al.; Eight new solid complexes of pipemidic acid (PPA) with trichlorizated rare earth metals LaCl(3), CeCl(3), PrCl(3), NdCl(3), SmCl(3), TbCl(3), DyCl(3), and YCl(3) have been synthesized . The complexes were characterized by elemental analyses, IR, NMR, and molar conductance measurements . The general formulas of the complexes are {M(PPA)(4)}Cl(3) (M=Ce(III), Pr(III), Nd(III), Sm(III), Tb(III), Dy(III), Y(III)), and {La(PPA)(4)Cl}Cl(2) . At the same time, the antibacterial activities of PPA and four of its complexes were tested . The results show that PPA and its complexes all have inhibitory action against bacteria of Escherichia coli, Bacillus subtilis, Streptococcus pneumoniae, and Pseudomonas aeruginosa but not Staphylococcus aureus . We compared their antibacterial activities and found that the antibacterial activity of {La(PPA)(4)Cl}Cl(2) against S . pneumoniae is much stronger than that of PPA and the other complexes.

Bioorg Med Chem, 2003 May 29, 11(11), 2389 - 94
Synthesis of 9-oxime-11,12-carbamate ketolides through a novel N-deamination reaction of 11,12-hydrazonocarbamate ketolide; Denis A et al.; A series of 9-oxime-11,12-carbamate ketolides was synthesized for the first time through a key 11,12-hydrazonocarbamate intermediate that was first oximated and further deaminated to give the corresponding carbamate . The N-N bond cleavage was achieved through an original new reaction using glycoaldehyde dimer as deaminating reagent . The new compounds synthesized were shown to display improved antibacterial activities against Streptococcus pneumoniae and S . pyogenes resistant to erythromycin.

J Vet Diagn Invest, 2003 May, 15(3), 295 - 7
Descriptive epidemiology of late-term abortions associated with the mare reproductive loss syndrome in central Kentucky; Cohen ND et al.; Epidemiological and pathological findings of 433 late-term abortions associated with the mare reproductive loss syndrome (MRLS) in central Kentucky were identified by reviewing the records of the University of Kentucky Livestock Diseases Diagnostic Center . The distribution of dates of abortion was clustered during a brief period of time, presumably from a simultaneous environmental exposure . The most common pathological findings were microscopic pulmonary lesions consisting of squamous epithelial cells present in alveoli with or without concurrent infiltration of inflammatory cells (neutrophils, macrophages, or monocytes) in the interstitium or within alveoli . Isolation of a non-beta-hemolytic Streptococcus (52% of fetuses) or an Actinobacillus sp . (19% of fetuses) was common . Placentitis or funisitis was identified in 44% of fetuses . No single pathological finding, however, was pathognomonic for MRLS-associated late-term abortion . This report describes the pathological findings characterizing the MRLS-associated abortion . A cause of MRLS could not be determined from necropsy findings.

J Biomed Mater Res A, 2003 May 1, 65(2), 203 - 8
Antibacterial characteristics of newly developed amphiphilic lipids and DNA-lipid complexes against bacteria; Inoue Y et al.; The purpose of this study was to investigate the antibacterial activity of newly developed amphiphilic lipids and DNA/lipid complexes against two types of oral bacteria and two types of hospital infection bacteria . Nine amphiphilic lipids were quantitatively prepared from the reaction of n-alkyl alcohol, alpha-amino acids, and p-toluenesulfonic acid . Nine DNA-lipid complexes were prepared by the simple mixing of DNA and amphiphilic lipids . The DNA-lipid complexes were insoluble in water . The antibacterial activity of lipids and DNA-lipid complexes against Porphyromonas gingivalis, Streptococcus mutans, Staphylococcus aureus, and Pseudomonas aeruginosa were evaluated by the disk-diffusion method . Seven artificial lipids showed antibacterial behavior; in particular, the lipids prepared from n-decyl alcohol and glycine and from n-decyl alcohol and L-alanine showed antibacterial activity against the four bacterial strains used in this study . On the other hand, the lipids of glutamic acid derivatives did not show any antibacterial activity against the four bacteria strains except for the lipid with an n-octyl group . Five DNA-lipid complexes also had an antibacterial effect . The complex prepared from DNA and glycine decyl ester p-toluenesulfonic acid salt exhibited antibacterial activity against the four types of bacteria strains . In this study it was found that lipids and DNA-lipid complexes with a mono-decyl group or a mono-dodecyl group have more favorable antibacterial activity .

Heart Lung, 2003 Mar-Apr, 32(2), 140 - 3
Streptococcal viridans subacute bacterial endocarditis associated with antineutrophil cytoplasmic autoantibodies (ANCA); de Corla-Souza A et al.; We report an illustrative case of a 60-year-old man with Streptococcus viridans subacute bacterial endocarditis (SBE) and positive antineutrophil cytoplasmic autoantibodies (c-ANCA) . C-ANCA positivity has been associated with a variety of rheumatic and infectious disease areas, but has been rarely associated with SBE . The patient had mitral valve prolapse with mitral regurgitation, and S viridans SBE developed after a dental procedure . Laboratory abnormalities included anemia, elevated erythrocyte sedimentation rate, positive rheumatoid factor, positive anticardiolipin antibody, positive lupus anticoagulant, and highly elevated c-ANCA level . We believe this is only the ninth reported case of S viridans SBE with a positive c-ANCA, and the third with mitral valve prolapse and vegetations.

Curr Opin Infect Dis, 2003 Apr, 16(2), 153 - 9
Severe community-acquired pneumonia: what's in a name?
Oosterheert JJ, Bonten MJ, Hak E, Schneider MM, Hoepelman AI.
PURPOSE OF REVIEW: Formerly, patients with community-acquired pneumonia admitted to an intensive care unit were considered as having the severe form of the disease . Recently, guidelines have distinguished severe and non-severe community-acquired pneumonia based on clinical definitions . In this review, we describe the different definitions of severe community-acquired pneumonia, and whether a differentiation based on these definitions reflects variation in etiology, risk factors, diagnostic approaches and treatment . RECENT FINDINGS: New definitions do not seem to accurately identify patients with high risks of mortality; patients not admitted to an intensive care unit could also be diagnosed as having severe community-acquired pneumonia . Host-factors, such as genetic factors and underlying diseases, can influence severity of presentation of community-acquired pneumonia . Distribution of pathogens in severe and non-severe disease forms is comparable . Initial antibiotic therapy in patients with severe disease should provide coverage of Streptococcus pneumoniae and Legionella pneumophila, as delay is associated with worse outcomes . However, recent studies also suggested an additional benefit of atypical coverage in non-severe disease . As a result, initial therapy with a beta-lactam plus a macrolide or an anti-pneumococcal fluoroquinolone is recommended for all patients with community-acquired pneumonia . Furthermore, the value of vaccination against pneumococci to prevent episodes of severe disease is yet unknown . SUMMARY: As current guidelines do not adequately identify patients with high risk of mortality and intensive care unit admittance, clinical judgment remains important . Based on distribution of pathogens, investigational procedures and therapy recommended in recent guidelines, differentiation between severe and non-severe community-acquired pneumonia does not seem useful . Whether atypical coverage indeed has additional value in non-severe or pneumococcal CAP, however, remains to be determined . In addition, the preventive benefit of influenza and pneumococcal vaccination for development of SCAP awaits further evidence.

J Clin Microbiol, 2003 May, 41(5), 2258 - 60
Peripartum transmission of penicillin-resistant Streptococcus pneumoniae; McDonald LC et al.; Streptococcus pneumoniae is a rarely recognized cause of neonatal sepsis . We present a recent case of S . pneumoniae bacteremia acquired on the first day of life in a neonate born at 30 weeks of gestation to a mother without prenatal care who had prolonged rupture of the membranes and received intravenous ampicillin prior to delivery . The isolate was resistant to penicillin, with a MIC of the drug of 4 microg/ml . The child responded to a 7-day course of intravenous vancomycin . S . pneumoniae was recovered from the vagina of the mother on a swab culture collected prior to delivery, and isolates from mother and child were confirmed to be identical on the basis of pulsed-field gel electrophoresis . Although neonatal sepsis due to the peripartum transmission of S . pneumoniae is rare, this case highlights the concern that increasing efforts to prevent group B streptococcus neonatal disease may lead to an increase in neonatal infections due to resistant organisms.

J Clin Microbiol, 2003 May, 41(5), 2166 - 9
A serotype V clone is predominant among erythromycin-resistant Streptococcus agalactiae isolates in a southwestern region of Germany; von Both U et al.; One hundred ninety-three Streptococcus agalactiae isolates of neonatal origin and 146 isolates from adult women were analyzed for macrolide resistance and investigated for clonality . Among erythromycin-resistant isolates, serotype V turned out to be the most frequent . Comparative pulsed-field gel electrophoresis analysis revealed genetic clustering of resistant strains and predominance of a single clone family within an otherwise heterogeneous serotype V population.

J Can Dent Assoc, 2003 May, 69(5), 304 - 7
Causes, treatment and prevention of early childhood caries: a microbiologic perspective; Berkowitz RJ; Early childhood caries (ECC) is a virulent form of dental caries that can destroy the primary dentition of toddlers and preschool children . It occurs worldwide, afflicting predominantly disadvantaged children . High-risk North American populations include Hispanic and Native American children, as well as children enrolled in Head Start, a federally funded program for preschool children living in poverty . The prevalence of EEC among these children ranges from 11% to 72% . ECC is an infectious disease, and Streptococcus mutans is the most likely causative agent; diet also plays a critical role in the acquisition and clinical expression of this infection . Early acquisition of S . mutans is a key event in the natural history of the disease . Acquisition may occur via vertical or horizontal transmission . Primary oral colonization by S . mutans coupled with caries-promoting feeding behaviours results in accumulation of these organisms to levels exceeding 30% of the total cultivable plaque flora which in turn leads to rapid demineralization of tooth structure . Treatment of ECC is costly because the cooperative capacity of babies and preschool children usually necessitates the use of general anesthesia . Treatment usually consists of restoration or surgical removal of carious teeth along with recommendations regarding feeding habits . However, this approach has resulted in unacceptable clinical outcomes, and relapse rates of approximately 40% have been reported within the first year after dental surgery . Primary prevention of ECC has largely been restricted to counselling parents about caries-promoting feeding behaviours . This approach has also had minimal success . Newer strategies addressing the infectious component through use of topical antimicrobial therapy appear promising.

Hua Xi Yi Ke Da Xue Xue Bao, 2001 Mar, 32(1), 15 - 7
{Expression of pyruvate oxidase gene sopox from Streptococcus sanguis in E . coli}; Hou B et al.; OBJECTIVE: To reconstruct the expression plasmid of Sopox gene for further understanding the regulation of its expression . METHODS: Sopox was recombined with expression vector pBV220 and the expression of Sopox in E . coli JM105 was observed after transformation . RESULTS: pBV220/Sopox/JM105 expressed a protein with molecular weight of 65 kd on SDS-PAGE after induction, and the expression reached the maximal amount with induction at 42 degrees C for 4 hours . CONCLUSION: Sopox was successfully cloned into pBV220 and expressed in E . coli JM105.

Appl Environ Microbiol, 2003 May, 69(5), 2737 - 47
Purification and characterization of streptin, a type A1 lantibiotic produced by Streptococcus pyogenes; Wescombe PA et al.; Approximately 10% of Streptococcus pyogenes strains inhibit the growth of all nine indicators in a standardized streptococcal bacteriocin typing scheme . The present study has shown that this inhibitory profile, referred to as bacteriocin producer (P)-type 777 activity, is due to the type A1 lantibiotic streptin . Two major forms of streptin were purified to homogeneity from 95% acidified (pH 2) methanol extracts of S . pyogenes M25 cells by using a series of reversed-phase chromatographic separations . The fully processed form of streptin (streptin 1) is a 23-amino-acid peptide with a mass of 2,424 Da . The 2,821-M(r) form of the peptide (streptin 2) has three additional amino acids (TPY) at the N terminus . Strain M25 extracts also contained small quantities of the streptin 1 and streptin 2 peptides in various stages of dehydration . Streptin 1 and streptin 2 were each capable of specifically inducing streptin production when added to strain M25 cultures . The streptin gene cluster resembled that of other type A1 lantibiotics but appeared to lack a streptin-specific proteinase gene . Although the streptin structural gene (srtA) was widespread within S . pyogenes, being detected in 40 of 58 strains, each representing a different M serotype, only 10 of these srtA-positive strains produced active streptin . The failure of some strains to express streptin was attributed to an approximately 4.5-kb deletion in their streptin loci, encompassing genes putatively encoding proteins involved in streptin processing (srtB and srtC) and transport (srtT) . In other strains, srtA transcription appeared to be defective . No direct association could be detected between the production of streptin and the production of the lantibiotic-like hemolysin streptolysin S in strain M25.

J Bacteriol, 2003 May, 185(10), 3009 - 19
Mutational analysis of the carboxy-terminal (YGX)4 repeat domain of CpsD, an autophosphorylating tyrosine kinase required for capsule biosynthesis in Streptococcus pneumoniae; Morona JK et al.; In Streptococcus pneumoniae, CpsB, CpsC, and CpsD are essential for encapsulation, and mutants containing deletions of cpsB, cpsC, or cpsD exhibit rough colony morphologies . CpsD is an autophosphorylating protein-tyrosine kinase, CpsC is required for CpsD tyrosine phosphorylation, and CpsB is a phosphotyrosine-protein phosphatase . We have previously shown that autophosphorylation of CpsD at tyrosine attenuates its activity and consequently reduces the level of encapsulation and negatively regulates CPS production . In this study, we further investigated the role of the carboxy-terminal (YGX)(4) repeat domain of CpsD in encapsulation . A CpsD truncation mutant in which the entire (YGX)(4) repeat domain was removed was indistinguishable from a strain in which the entire cpsD gene had been deleted, indicating that the carboxy-terminal (YGX)(4) tail is required for CpsD activity in capsular polysaccharide production . Double mutants having a single tyrosine residue at position 2, 3, or 4 in the (YGX)(4) repeat domain and lacking CpsB exhibited a rough colony morphology, indicating that in the absence of an active protein-tyrosine phosphatase, phosphorylation of just one of the tyrosine residues in the (YGX)(4) repeat was sufficient to inactivate CpsD . When various mutants in which CpsD had either one or combinations of two or three tyrosine residues in the (YGX)(4) repeat domain were examined, only those with three tyrosine residues in the (YGX)(4) repeat domain were indistinguishable from the wild-type strain . The mutants with either one or two tyrosine residues exhibited mucoid colony morphologies . Further analysis of the mucoid strains indicated that the mucoid phenotype was not due to overproduction of capsular polysaccharide, as these strains actually produced less capsular polysaccharide than the wild-type strain . Thus, the tyrosine residues in the (YGX)(4) repeat domain are essential for normal functioning of CpsD.

J Antimicrob Chemother, 2003 May, 51 Suppl 2, ii27 - 35
Efficacy of linezolid versus comparator therapies in Gram-positive infections; Wilcox MH; Treatment of Gram-positive bacterial infections is currently a therapeutic challenge because many of these pathogens are now resistant to standard antimicrobial agents . The emergence of multidrug-resistant, Gram-positive pathogens emphasizes the need for new antimicrobial therapy . Linezolid is an oxazolidinone antibiotic with a novel mechanism of action that works by inhibiting bacterial protein synthesis by blocking formation of the initiation complex . It is active against Gram-positive organisms resistant to other antibiotics, including methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae and vancomycin-resistant enterococci (VRE) . Results are encouraging from several large-scale, randomized, Phase III trials comparing the efficacy and safety of linezolid with standard comparator agents for the treatment of nosocomial pneumonia, community-acquired pneumonia, skin and skin structure infections, and infections due to MRSA and VRE . Intravenous/oral linezolid is a promising antimicrobial agent and provides the clinician with an additional treatment option, particularly among the limited therapies for resistant Gram-positive bacterial infections.

Diagn Microbiol Infect Dis, 2003 Apr, 45(4), 273 - 8
Comparative activity of garenoxacin (BMS 284756), a novel desfluoroquinolone, tested against 8,331 isolates from community-acquired respiratory tract infections: North American results from the SENTRY Antimicrobial Surveillance Program (1999-2001); Jones RN et al.; Emerging resistances to orally administered antimicrobials have escalated among bacteria causing community-acquired respiratory infections (CARTI) . The spectrum and potency of garenoxacin, (formerly BMS 284756) was assessed against a collection of CARTI isolates from North American medical centers during a longitudinal surveillance study, the SENTRY Antimicrobial Surveillance Program (1999-2001) . A total of 8,331 strains of Hemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae were tested by reference methods and compared to numerous other marketed antimicrobials . Nearly all (95.1%) M . catarrhalis were penicillin-resistant, 27.9% of H . influenzae were ampicillin-resistant and 35.0% of S . pneumoniae had MICs at > or = 0.12 microg/ml for penicillin . Garenoxacin was very active against the three monitored species with MIC(90) values of < or =0.06 microg/ml . Garenoxacin and other quinolones were equally active against the Gram-negative pathogens (except moxifloxacin which was at least twofold less potent versus M . catarrhalis) . However, against pneumococci the rank order of potency (MIC(50) in microg/ml) was: gemifloxacin (0.015) > garenoxacin (0.06) > trovafloxacin = moxifloxacin (0.12) > gatifloxacin (0.25) > levofloxacin = ciprofloxacin (1) . A trend toward greater resistance worldwide was observed for ciprofloxacin (MIC, > or = 4 microg/ml), increasing from 1.5% in 1999 to 6.8% in 2001 . The highest quinolone resistance rate was observed in North America . Garenoxacin, a new desfluoro(6)quinolone, was documented to be very active in vitro (MIC, < or =2 microg/ml) against > 99.9% of all CARTI isolates in the SENTRY Program . Evolving resistances to other antimicrobial classes or among currently used quinolones appear to position this investigational desfluoro(6)quinolone as a potential treatment option for future clinical use in ambulatory patients.

Diagn Microbiol Infect Dis, 2003 Apr, 45(4), 265 - 7
Mutation prevention concentration of ceftriaxone, meropenem, imipenem, and ertapenem against three strains of Streptococcus pneumoniae; Hovde LB et al.; This investigation tested the mutation prevention concentration (MPC) concept using imipenem, meropenem, ceftriaxone, and ertapenem against three strains of Streptococcus pneumoniae (PCN MIC = 0.012, 1, 8 mg/L, respectively) . MIC, MBC, and MPC values for each of the beta-lactams did not differ by more than one tube dilution . While an interesting concept, MPC may not apply to antimicrobials that do not utilize a dual targeting system, such as beta-lactams, or to bacteria that exhibit multiple mechanisms of resistance and/or mutate at a rate where the frequency would likely be captured by the standard inoculum size used in routine MIC testing.

Diagn Microbiol Infect Dis, 2003 Apr, 45(4), 251 - 9
Antimicrobial susceptibility of community-acquired respiratory tract pathogens in North America in 1999-2000: findings of the PROTEKT surveillance study; Hoban D et al.; The PROTEKT surveillance study commenced in 1999 to examine the antimicrobial susceptibility of community-acquired respiratory pathogens . We report here the results from 2371 isolates collected during 2000 by North American centers (Canada, n = 7; USA, n = 8) . Overall, 21.3% of pneumococci (n = 687) were penicillin G-resistant (Canada, 10.3%; USA, 32.6%) . Corresponding rates of erythromycin resistance were 16.3% and 31.5% . Telithromycin inhibited all penicillin- and erythromycin-resistant isolates at < or =1 microg/ml . Among 612 Hemophilus influenzae isolates, 22.4% were beta-lactamase-positive . Antimicrobial susceptibility of H . influenzae varied between 82.4% (clarithromycin) and 100% (cefpodoxime, levofloxacin) . Importantly, one isolate was found to be resistant to both moxifloxacin and ciprofloxacin . Most Moraxella catarrhalis isolates were highly susceptible to the antimicrobials tested, except ampicillin . All Streptococcus pyogenes isolates (n = 382) were penicillin-susceptible and 5.2% were non-susceptible to erythromycin . S . pyogenes showed cross-resistance to other macrolides yet remained inhibited by telithromycin at < or =0.5 microg/ml . Methicillin resistance among Staphylococcus aureus was common (19.9%), particularly in the USA . The PROTEKT study confirms the widespread prevalence of antimicrobial resistance among common respiratory pathogens in North America, and hence the need for continued surveillance to guide optimal empiric therapy for community-acquired respiratory tract infections.

Protein Expr Purif, 2003 May, 29(1), 77 - 84
A novel member of glycoside hydrolase family 88: overexpression, purification, and characterization of unsaturated beta-glucuronyl hydrolase of Bacillus sp . GL1; Mori S et al.; Unsaturated beta-glucuronyl hydrolase of Bacillus sp . GL1 catalyzes the hydrolytic release of unsaturated glucuronic acids from oligosaccharides produced through the reactions of polysaccharide lyases such as gellan, xanthan, hyaluronate, and chondroitin lyases . An overexpression system for the enzyme was constructed in Escherichia coli cells involving regulation of the enzyme gene under the T7 promoter and terminator . The expression level of the enzyme in E . coli cells was 250-fold higher than that in Bacillus sp . GL1 cells . The enzyme expressed in E . coli cells was purified and characterized . The optimal pH and temperature, and substrate specificity of the purified enzyme were similar to those of the native enzyme from Bacillus sp . GL1 cells, although the enzyme expressed in E . coli cells underwent self-assembly into polymeric forms through the formation of intermolecular disulfide bonds . Circular dichroism analysis indicated that the secondary structure of the enzyme was rich in alpha-helices . Genes showing high identity (over 40% identity) with that of the enzyme were found in the genomes of some pathogenic bacteria, such as Streptococcus pyogenes and Streptococcus pneumoniae, which cause serious diseases (e.g., meningitis and pneumonia) . Therefore, the enzyme of Bacillus sp . GL1 and the streptococcal proteins form a new glycoside hydrolase family, 88.

Epidemiol Infect, 2003 Apr, 130(2), 335 - 49
Clinical, epidemiological and molecular characteristics of Streptococcus uberis infections in dairy herds; Zadoks RN et al.; A longitudinal observational study (18 months) was carried out in two Dutch dairy herds to explore clinical, epidemiological and molecular characteristics of Streptococcus uberis mastitis . Infections (n = 84) were detected in 70 quarters of 46 cows . Bacterial isolates were characterized at strain level by random amplified polymorphic DNA (RAPD) fingerprinting . Persistent infections were usually attributable to one strain, while recurrent infections could be caused by different strains . When multiple quarters of a cow were infected, infections were mostly caused by one strain . In each herd, multiple strains were identified yet one strain predominated . The majority of all infections were subclinical, and infections attributed to predominant strains were more chronic than infections attributed to other strains . Epidemiological and molecular data suggest infection from environmental sources with a variety of S . uberis strains as well as within-cow and between-cow transmission of a limited number of S . uberis strains, with possible transfer of bacteria via the milking machine.

No To Shinkei, 2003 Mar, 55(3), 269 - 72
{A survival case of fluminant meningitis and multiple organ failure as overwhelming postsplenectomy infection (OPSI) syndrome}; Takazawa H et al.; A 39-year-old man, who had splenectomy following abdominal trauma 30 years previously, admitted to our hospital with high fever, headache and convulsion on January 8, 2002 . Examination of cerebrospinal fluid (CSF) showed pleocytosis up to 10,000 cells/mm3 with polymorphonuclear cells dominant and elevated protein to 330 mg/dl and reduction of glucose to 15 mg/dl . Streptococcus pneumoniae was detected at the culture of CSF and blood . We diagnosed him as having pneumococcal meningitis as overwhelming postsplenectomy infection(OPSI) syndrome . After administration of carbapenem antibiotics, methylprednisolone (1,000 mg) and immunoglobulin, he survived without any complications . Splenectomized patients are likely to suffer from severe infections, such as sepsis and meningitis, which is called OPSI syndrome . The course is rapid, the clinical symptoms are serious, and the prognosis is very poor . It is important for splenectomized patients to receive the vaccine, antibiotic prophylaxis and seek medical attention at the earliest sign of minor infection.

FEMS Immunol Med Microbiol, 2003 May 15, 36(1-2), 111 - 3
Genetic analysis of Streptococcus agalactiae strains isolated from neonates and their mothers; Melchers WJ et al.; Streptococcus agalactiae or group B streptococcus (GBS) is the most common cause of neonatal sepsis and meningitis in neonates . One of the major questions is whether the GBS strains able to cause neonatal invasive disease have peculiar genetic features . A collection of S . agalactiae strains, isolated from cervix, vagina and rectum of 10 mothers and from throat, ear and umbilicus of their newborns was genetically characterized by pulsed-field gel electrophoresis (PFGE) . This study demonstrated that the strains isolated from each mother and her child were all genetically identical but that the strains from the 10 mother/child pairs mutually were genetically heterogeneous and 10 different PFGE patterns were found . Although it has been suggested that PFGE would be able to identify virulence traits to direct decisions in antibiotic management, the heterogeneous feature of GBS strains does not support broad application.

Int J Cardiol, 2003 May, 89(1), 63 - 70
Duration of symptoms in patients with infective endocarditis; Sarli Issa V et al.; Despite progress in the management of infective endocarditis, delays in diagnosis or prior antimicrobial treatment may adversely influence the symptom duration and outcome . The duration of symptoms in patients with infective endocarditis was studied in 683 cases among 653 patients with 703 episodes of the disease; patients were hospitalized within 10 days of symptom onset in 169 (24.7%) cases . Antimicrobial therapy before hospital admission was administered to 257 (36.5%) patients . Overall mortality was 25.6% . Symptom duration was longer when antimicrobials were administered before diagnosis (58.8+/-78.1 vs . 44.8+/-54.9 days), when vegetations were detected on echocardiogram (53.5+/-68.2 vs . 38.8+/-47.3) and among patients admitted before 1990 (42.3+/-67.1 vs . 54.2+/-62.4 days) . Symptom duration was shorter in patients with prosthetic valve endocarditis (26.8+/-34.2 vs . 59.3+/-71.6 days) . In 54 (26.5%) episodes of prosthetic valve endocarditis, patients had symptoms for more than 30 days . Staphylococcus aureus was the most frequent agent among patients with symptoms up to 10 days (41.2%) and Streptococcus among those with symptoms over 20 days (53.9%) . Symptom duration did not significantly differ in regard to medical (51.3+/-69.2 days) or surgical (46.7+/-55.7 days) treatment . Mortality increased as symptom duration decreased and was highest for patients who experienced symptoms for less than 10 days (36.1%) . In some patients medical care may be delivered relatively late in the course of infective endocarditis . Administration of antibiotics previous to hospital admission increased duration of symptoms, and cardiac valve prosthesis, staphylococcal infection and death were associated with more acute disease.

Plasmid, 2003 Mar, 49(2), 143 - 51
Chloramphenicol resistance transposable element TnSs1 of Streptococcus suis, a transposon flanked by IS6-family elements; Takamatsu D et al.; A new transposon, designated TnSs1, which contains a chloramphenicol acetyltransferase gene flanked by direct repeats of an IS6-family element was found in a field isolate of Streptococcus suis . Polymerase chain reaction and hybridization analyses indicated that another field isolate carried the same transposon in a different location on the chromosome . A transposition assay done with a thermosensitive suicide vector showed that, among the seven TnSs1 mutants tested in this study, six formed a cointegrate between the S . suis genome and the vector with the generation of the third copy of the insertion sequence element, and one harbored one copy of TnSs1 on the chromosome as a result of a subsequent resolution step . On transposition, TnSs1 duplicated an 8-bp sequence at the target site.

FEMS Microbiol Lett, 2003 Apr 25, 221(2), 277 - 84
Homocysteine biosynthesis pathways of Streptococcus anginosus; Yoshida Y et al.; A gene (cgs) encoding cystathionine gamma-synthase was cloned from Streptococcus anginosus, and its protein was purified and characterized . The cgs gene and the immediately downstream lcd gene were shown to be cotranscribed as an operon . High-performance liquid chromatography analyses showed that the S . anginosus Cgs not only has cystathionine gamma-synthase activity, but also expresses O-acetylhomoserine sulfhydrylase activity . These results suggest that S . anginosus has the capacity to utilize both the transsulfuration and direct sulfhydrylation pathways for homocysteine biosynthesis.

Microbiol Immunol, 2003, 47(3), 213 - 5
The role of glucan-binding proteins in the cariogenicity of Streptococcus mutans; Matsumura M et al.; Streptococcus mutans produces glucan-binding proteins (Gbps), which appear to contribute to the virulence of S . mutans . GbpA and GbpC genes were inactivated by the insertion of antibiotic-resistant genes into each gbp gene of S . mutans MT8148 to generate Gbp-defective mutants . Sucrose dependent adherences of the GbpA- and GbpC-defective mutants were found to be significantly lower than those of their parent strains MT8148 . Caries inducing activity of the mutants in rats was significantly lower than that of strain MT8148R (streptomycin-resistant strain of MT8148) . These results suggest that GbpA and GbpC participate in cellular adherence to tooth surfaces and contribute to the cariogenicity of S . mutans.

J Am Soc Echocardiogr, 2003 May, 16(5), 497 - 8
Transesophageal echocardiographic identification of an aortic root to right atrial fistula in a patient with acute streptococcal aortic valve bacterial endocarditis; Novak PG et al.; We describe the case of a patient with acute aortic valve endocarditis complicated by aortic insufficiency, perivalvular abscess, and aortic root to right atrial fistula caused by Streptococcus pneumoniae bacterial infective endocarditis . Although typically of low sensitivity for the diagnosis of myocardial abscess and similar complications of infective endocarditis, transthoracic echocardiogram successfully identified this relatively uncommon complication that was later confirmed by transesophageal echocardiography and at time of operation.

N Engl J Med, 2003 May 1, 348(18), 1747 - 55
Effectiveness of pneumococcal polysaccharide vaccine in older adults; Jackson LA et al.; BACKGROUND: Streptococcus pneumoniae is the chief cause of pneumonia in older adults, but it remains unclear whether use of the pneumococcal polysaccharide vaccine alters the overall risk of community-acquired pneumonia . In a large population of older adults, we assessed the effectiveness of the pneumococcal vaccine . METHODS: In this retrospective cohort study, 47,365 Group Health Cooperative members 65 years of age or older were assessed over a three-year period . The primary outcomes were hospitalization because of community-acquired pneumonia (validated by chart review), pneumonia in patients who were not hospitalized ("outpatient pneumonia," determined from administrative data sources), and pneumococcal bacteremia . The association between pneumococcal vaccination and the risk of each outcome was evaluated by means of multivariate Cox proportional-hazards models, with adjustment for age, sex, nursing-home residence or nonresidence, smoking status, medical conditions, and receipt or nonreceipt of influenza vaccine . RESULTS: During the study period, 1428 cohort members were hospitalized with community-acquired pneumonia, 3061 were assigned a diagnosis of outpatient pneumonia, and 61 had pneumococcal bacteremia . Receipt of the pneumococcal vaccine was associated with a significant reduction in the risk of pneumococcal bacteremia (hazard ratio, 0.56; 95 percent confidence interval, 0.33 to 0.93) but a slightly increased risk of hospitalization for pneumonia (hazard ratio, 1.14; 95 percent confidence interval, 1.02 to 1.28) . Pneumococcal vaccination did not alter the risk of outpatient pneumonia (hazard ratio, 1.04; 95 percent confidence interval, 0.96 to 1.13) or of any case of community-acquired pneumonia, whether or not it required hospitalization (hazard ratio, 1.07; 95 percent confidence interval, 0.99 to 1.14) . CONCLUSIONS: These findings support the effectiveness of the pneumococcal polysaccharide vaccine for the prevention of bacteremia, but they suggest that alternative strategies are needed to prevent nonbacteremic pneumonia, which is a more common manifestation of pneumococcal infection in elderly persons .

N Engl J Med, 2003 May 1, 348(18), 1737 - 46
Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine; Whitney CG et al.; BACKGROUND: In early 2000, a protein-polysaccharide conjugate vaccine targeting seven pneumococcal serotypes was licensed in the United States for use in young children . METHODS: We examined population-based data from the Active Bacterial Core Surveillance of the Centers for Disease Control and Prevention to evaluate changes in the burden of invasive disease, defined by isolation of Streptococcus pneumoniae from a normally sterile site . Serotyping and susceptibility testing of isolates were performed . We assessed trends using data from seven geographic areas with continuous participation from 1998 through 2001 (population, 16 million) . RESULTS: The rate of invasive disease dropped from an average of 24.3 cases per 100,000 persons in 1998 and 1999 to 17.3 per 100,000 in 2001 . The largest decline was in children under two years of age . In this group, the rate of disease was 69 percent lower in 2001 than the base-line rate (59.0 cases per 100,000 vs . 188.0 per 100,000, P<0.001); the rate of disease caused by vaccine and vaccine-related serotypes declined by 78 percent (P<0.001) and 50 percent (P<0.001), respectively . Disease rates also fell for adults; as compared with base line, the rate of disease in 2001 was 32 percent lower for adults 20 to 39 years of age (7.6 cases per 100,000 vs . 11.2 per 100,000, P<0.001), 8 percent lower for those 40 to 64 years of age (19.7 per 100,000 vs . 21.5 per 100,000, P=0.03), and 18 percent lower for those 65 years of age or more (49.5 per 100,000 vs . 60.1 per 100,000, P<0.001) . The rate of disease caused by strains that were not susceptible to penicillin was 35 percent lower in 2001 than in 1999 (4.1 cases per 100,000 vs . 6.3 per 100,000, P<0.001) . CONCLUSIONS: The use of the pneumococcal conjugate vaccine is preventing disease in young children, for whom the vaccine is indicated, and may be reducing the rate of disease in adults . The vaccine provides an effective new tool for reducing disease caused by drug-resistant strains .

Microbiology, 2003 May, 149(Pt 5), 1333 - 40
The LicT protein acts as both a positive and a negative regulator of loci within the bgl regulon of Streptococcus mutans; Cote CK et al.; An open reading frame (ORF) that would encode a putative antiterminator protein (LicT) of the BglG family was identified in the genomic DNA sequence of Streptococcus mutans . A DNA sequence that would encode a potential ribonucleic antiterminator (RAT) site in the mRNA at which the putative antitermination protein LicT would bind was located immediately downstream from this ORF . These putative antitermination components are upstream of a glucose-independent beta-glucoside-utilization system that is responsible for aesculin utilization by S . mutans NG8 in the presence of glucose . It was hypothesized that these putative regulatory components were an important mechanism that was involved with the controlled expression of the S . mutans bglP locus . A strain of S . mutans containing a licT : : Omega-Kan2 insertional mutation was created . This strain could not hydrolyse aesculin in the presence of glucose . The transcriptional activity associated with other genes from the bgl regulon was determined in the licT : : Omega-Kan2 genetic background using lacZ transcriptional fusions and beta-galactosidase assays to determine the effect of LicT on these loci . The LicT protein had no significant effect on the expression of the bglC promoter, a regulator of the bglA locus . However, it is essential for the optimal expression of bglP . These data correlate with the phenotype observed on aesculin plates for the S . mutans wild-type strain NG8 and the licT : : Omega-Kan2 strain . Thus, the glucose-independent beta-glucoside-specific phosphotransferase system (PTS) regulon in S . mutans relies on LicT for BglP expression and, in turn, aesculin transport in the presence of glucose . Interestingly, LicT also seems to negatively regulate the expression of the bglA promoter region . In addition, the presence of the S . mutans licT gene has been shown to be able to activate a cryptic beta-glucoside-specific operon found in Escherichia coli.

Microbiology, 2003 May, 149(Pt 5), 1083 - 93
Genetic relatedness and phenotypic characteristics of Treponema associated with human periodontal tissues and ruminant foot disease; Edwards AM et al.; Treponema have been implicated recently in the pathogenesis of digital dermatitis (DD) and contagious ovine digital dermatitis (CODD) that are infectious diseases of bovine and ovine foot tissues, respectively . Previous analyses of treponemal 16S rDNA sequences, PCR-amplified directly from DD or CODD lesions, have suggested relatedness of animal Treponema to some human oral Treponema species isolated from periodontal tissues . In this study a range of adhesion and virulence-related properties of three animal Treponema isolates have been compared with representative human oral strains of Treponema denticola and Treponema vincentii . In adhesion assays using biotinylated treponemal cells, T . denticola cells bound in consistently higher numbers to fibronectin, laminin, collagen type I, gelatin, keratin and lactoferrin than did T . vincentii or animal Treponema isolates . However, animal DD strains adhered to fibrinogen at equivalent or greater levels than T . denticola . All Treponema strains bound to the amino-terminal heparin I/fibrin I domain of fibronectin . 16S rDNA sequence analyses placed ovine strain UB1090 and bovine strain UB1467 within a cluster that was phylogenetically related to T . vincentii, while ovine strain UB1466 appeared more closely related to T . denticola . These observations correlated with phenotypic properties . Thus, T . denticola ATCC 35405, GM-1, and Treponema UB1466 had similar outer-membrane protein profiles, produced chymotrypsin-like protease (CTLP), trypsin-like protease and high levels of proline iminopeptidase, and co-aggregated with human oral bacteria Porphyromonas gingivalis and Streptococcus crista . Conversely, T . vincentii ATCC 35580, D2A-2, and animal strains UB1090 and UB1467 did not express CTLP or trypsin-like protease and did not co-aggregate with P . gingivalis or S . crista . Taken collectively, these results suggest that human oral-related Treponema have broad host specificity and that similar control or preventive strategies might be developed for human and animal Treponema-associated infections.

J Med Chem, 2003 May 8, 46(10), 1905 - 17
A novel antibacterial 8-chloroquinolone with a distorted orientation of the N1-(5-amino-2,4-difluorophenyl) group; Kuramoto Y et al.; Fluoroquinolones represent a major class of antibacterial agents with great therapeutic potential . In this study, we designed m-aminophenyl groups as novel N-1 substituents of naphthyridones and quinolones . Among newly synthesized compounds, 7-(3-aminoazetidin-1-yl)-1-(5-amino-2,4-difluorophenyl)-8-chloro-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (4) has extremely potent antibacterial activities against Gram (+) as well as Gram (-) bacteria . This compound is significantly more potent than trovafloxacin against clinical isolates: 30 times against Streptococcus pneumoniae and 128 times against methicillin resistant Staphylococcus aureus . The structure-activity relationship (SAR) study revealed that a limited combination of 1-(5-amino-2,4-difluorophenyl) group, 7-(azetidin-1-yl) group, and 8-Cl atom (or Br atom or Me group) gave potent antibacterial activity . An X-ray crystallographic study of a 7-(3-ethylaminoazetidin-1-yl)-8-chloro derivative demonstrated that the N-1 aromatic group was remarkably distorted out of the core quinolone plane by steric repulsion between the C-8 Cl atom and the N-1 substituent . Furthermore, a molecular modeling study of 4 and its analogues demonstrated that a highly distorted orientation was induced by a steric hindrance of the C-8 substituent, such as Cl, Br, or a methyl group . Thus, their highly strained conformation should be a key factor for the potent antibacterial activity.

Jpn J Antibiot, 2003 Feb, 56(1), 27 - 35
{Alteration of antibacterial activity of tosufloxacin and various antibacterial agents against Streptococcus pneumoniae}; Maekawa M et al.; The minimum inhibitory concentrations (MICs) of tosufloxacin (TFLX), levofloxacin (LVFX), ciprofloxacin (CPFX), gatifloxacin (GFLX), sparfloxacin (SPFX), azithromycin (AZM), cefteram (CFTM), cefdinir (CFDN) and cefpodoxime (CPDX) against 337 clinical isolates of Streptococcus pneumoniae isolated from Japanese hospital from 1997 to 2002 were investigated by agar plate method . The incidence of penicillin-susceptible S . pneumoniae (PSSP), penicillin-intermediate resistant S . pneumoniae (PISP), and penicillin-resistant S . pneumoniae (PRSP) in each year was studied, and the MICs of antibacterial agents against these strains were determined . As the results, the total incidence of PSSP, PISP, and PRSP was 51.0%, 40.4% and 8.6%, respectively . The incidences of PSSP from 1997 to 2002 were 46.0-55.9%, and were almost definite in each year . In quinolone antibiotics, the differences of antibacterial activity among TFLX, SPFX, and GFLX against PSSP, PISP, and PRSP, were not observed, and these 3 quinolones had potent antibacterial activity . Although CPFX and LVFX showed antibacterial activity as well as other quinolones by 2001, the CPFX-resistant or LVFX-intermediate resistant strains of PSSP were seen with 56.5% and 91.3% in 2002, respectively . Thirty percents of each PSSP, PISP, and PRSP strains were AZM-resistant strains . Such tendency of increase was recognized in PSSP . Against cephem antibiotics, the incidence of intermediate resistant and resistant strains was higher for PISP and PRSP than for PSSP . No difference in the incidence of resistant strains was noted among CFTM, CFDN, and CPDX.

Acta Clin Belg, 2003 Jan-Feb, 58(1), 19 - 26
Antibiotic susceptibility and serotype distribution of 240 Streptococcus pneumoniae causing meningitis in Belgium 1997-2000; Verhaegen J et al.; Cerebrospinal fluid isolates of Streptococcus pneumoniae, collected during the years 1997-2000 at more than 100 Belgian laboratories were studied . The 10 most common serotypes-serogroups representing 76% of the isolates were 14, 6, 9, 19, 23, 18, 4, 10, 8 and 12 (in order of frequency) . Thirty-six percent of strains were isolated in children < 5 years old . In this age group the number of serogroups was more limited and 81.4% are included in the 7-valent conjugate vaccine . Decreased susceptibility to penicillin was observed in 13.9% of 237 strains (MIC > 0.06 mg/L), with only 2.1% resistant strains (MIC > 1 mg/L) . Twelve strains showed reduced susceptibility to cefotaxime (MIC > 0.5 mg/L) . Only three of the 237 strains were intermediately susceptible to meropenem . All strains were susceptible to vancomycin and moxifloxacin . In Belgium, high doses of third generation cephalosporins remain effective for the treatment of pneumococcal meningitis . The new fluoroquinolones seem the most promising agents for the treatment of pneumococcal meningitis in the future.

J Infect Dis, 2003 May 15, 187(10), 1629 - 38 Epub 2003 Apr 30.
Significant variation in serotype-specific immunogenicity of the seven-valent Streptococcus pneumoniae capsular polysaccharide-CRM197 conjugate vaccine occurs despite vigorous T cell help induced by the carrier protein; Kamboj KK et al.; Streptococcus pneumoniae capsular polysaccharides (PnPSs) induce protective antibodies but are T cell-independent type 2 antigens and are poorly immunogenic in infants . Conjugate vaccines of PnPSs linked to proteins like cross-reactive material (CRM(197)) increase PS antibody titer and elicit immunologic memory in infants . Despite being linked to an identical carrier protein, each PS component of the 7-valent PnPS-CRM(197) vaccine has different immunogenicity . To determine whether variations in conjugate-induced memory T cell responses or PnPS-specific antibody-secreting cells (ASCs) were responsible for serotype-specific differences in immunogenicity, adults were immunized with 7-valent PnPS-CRM(197), and antibody titer, vaccine component-specific CD4(+) T cell recall response, numbers of PnPS-specific ASCs, and cytokine production were measured . PnPS-CRM(197) induced significantly different serotype-specific antibody titers, despite vigorous T cell recall responses to all 7 vaccine components, and production of interleukin (IL)-2, IL-5, IL-6, IL-10, and interferon-gamma . We conclude that PnPS-CRM(197) induces variable serotype-specific antibody titers, despite induction of comparable CRM(197)-specific memory T cell responses.

J Infect Dis, 2003 May 15, 187(10), 1598 - 608 Epub 2003 Apr 30.
Protection against group A streptococcus by immunization with J8-diphtheria toxoid: contribution of J8- and diphtheria toxoid-specific antibodies to protection; Batzloff MR et al.; A conformationally constrained, minimally conserved peptide from the M protein of group A streptococcus (GAS) has been defined . It consists of 12 amino acids from the C-repeat region within a non-M protein helix-forming sequence and is referred to as "J8." Here, we investigate the immunogenicity of a J8-diphtheria toxoid (DT) conjugate adjuvanted with the human-compatible adjuvants, SBAS2 and alum, and demonstrate that it is capable of inducing opsonic antibodies and can protect outbred mice from virulent challenge . In a range of experiments, protection correlated with the titer of J8-specific antibodies and not with the induction of J8-specific T cells . However, DT-specific antibodies (as well as J8-specific antibodies) were shown to stain the surface of fixed GAS and to be capable of opsonizing live organisms . DT may be an ideal carrier protein for J8 and other GAS peptides for GAS vaccines.

Pediatr Surg Int, 2003 Apr, 19(1-2), 96 - 9 Epub 2003 Mar 29.
Evaluation of the protective effect of methotrexate on OK432-induced liver injury in a rat model; Alladi A et al.; Cholangitis-induced liver damage was created in rats by intraductal injection of OK432, a lyophilized incubation mixture of group A Streptococcus pyogenes of human origin . Oral, low-dose methotrexate (MTX) was given to one group to study its protective effect on liver injury . The liver histology was studied and semiquantitatively graded . The OK432-induced changes were compared with and without MTX therapy . The results revealed statistically significant higher grades of portal inflammation and sinusoidal infiltration in rats treated with OK432 compared to saline-treated controls . There was significant improvement in liver changes in the group treated with MTX compared to the untreated group . It could be concluded that oral, low-dose, pulsed MTX therapy caused significant improvement in cholangitis-induced liver damage in rats.

J Biol Chem, 2003 Jul 11, 278(28), 25509 - 16 Epub 2003 Apr 27.
Streptococcus pneumoniae hyaluronate lyase contains two non-cooperative independent folding/unfolding structural domains: characterization of functional domain and inhibitors of enzyme; Akhtar MS et al.; Hyaluronate lyase contributes directly to bacterial invasion by degrading hyaluronan, the major component of host extracellular matrix of connective tissues . Streptococcus pneumoniae hyaluronate lyase (SpnHL) is built from two structural domains that interact through interface residues, in addition to being connected by a peptide linker . For the first time we demonstrate that the N- and C-terminal domains of SpnHL fold/unfold independent of each other suggesting the absence of any significant cooperative interactions between them . The C-terminal domain of SpnHL is less stable than the N-terminal domain against thermal and guanidine hydrochloride denaturation . The intact N-terminal domain was purified after limited proteolysis of SpnHL under conditions where only the C-terminal domain was unfolded . Isolated N-terminal domain of SpnHL had similar thermal stability as when present in the native enzyme and was found to be enzymatically active demonstrating that it is capable of carrying out enzymatic reaction on its own . Functional studies demonstrated that guanidine hydrochloride, guanidine isothiocyanate, l-arginine methyl ester, and l-arginine inhibit the enzymatic activity of SpnHL at very low concentrations . This provides a lead for new chemical entities that can be exploited for designing effective inhibitors of SpnHL.

Int J Biol Macromol, 2003 Mar, 32(1-2), 23 - 7
Synthesis of chitooligosaccharide derivative with quaternary ammonium group and its antimicrobial activity against Streptococcus mutans; Kim JY et al.; A derivative of chitooligosaccharide (COS) with quaternary ammonium functionality was synthesized and characterized by means of FT-IR and NMR spectroscopy . Its amtimicrobial activity was evaluated against Streptococcus mutans, which is a principal etiological agent of dental caries in humans . Introduction of quaternary ammonium group to COS has been easily accomplished by coupling of glycidyl trimethylammonium chloride (GTMAC) to COS in aqueous solution without an additional catalyst . The degree of substitution (%), as determined by (1)H NMR, of GTMAC to the COS increased up to 116% at 70 degrees C for 24h . The resulting COS-GTMAC exhibited the growth inhibition of above 80% against S . mutans after 5h, whereas the COS showed the growth inhibition of about 10% . It was found that antimicrobial activity of the COS could be considerably enhanced by the introduction of quaternary ammonium functionality.

Eur J Intern Med, 2003 Mar, 14(2), 120 - 122
Recurrent valvular replacement due to exacerbation of Behcet's disease by Streptococcus agalactiae infection; Lellouche N et al.; Valvular heart complications in Behcet's disease are rarely reported . Moreover, the risk of dehiscence in postoperative valvular replacement is high in Behcet's disease . We report a case of recurrent aortic prosthetic dehiscence revealing Behcet's disease in a young woman . Each disease exacerbation was concomitant to a Streptococcus agalactiae infection . This infection appears to act as a trigger for Behcet's disease exacerbation . The patient was successfully treated with immunosuppression plus antibiotic therapy.

Int J Infect Dis, 2003 Mar, 7(1), 46 - 52
Bacteremic pneumococcal infections in immunocompromised patients without AIDS: the impact of beta-lactam resistance on mortality; Fernandez Guerrero ML et al.; BACKGROUND: Streptococcus pneumoniae is the leading cause of community-acquired pneumonia in the elderly, and in recent years it has arisen as an important pathogen in HIV-infected patients . However, there is a scarcity of information on clinical and therapeutic problems associated with pneumococcal infections in other immuno-compromised patients . The objective of this study was to assess the most relevant epidemiologic aspects, clinical features and prognostic factors of pneumococcal bacteremia in immunocompromised hosts without AIDS . METHODS: This was a retrospective analysis of patients with pneumococcemia, carried out in a 600-bed, university-affiliated hospital in Madrid, Spain . Two-hundred and sixty patients were evaluated retrospectively; 69 (26.5%) immunocompromised patients based on strict case definitions were compared with a group composed of 191 non-immunocompromised hosts with a variety of chronic conditions . Conventional management of pneumococcal bacteremia according to clinical standards was assessed . The MICs of penicillin and other beta-lactam antibiotics, and related mortality and hospital mortality at 30 days, were measured . RESULTS: A comparison of clinical manifestations of pneumococcemia between immunocompromised patients and non-immunocompromised patients did not show differences in the presence of fever, obtundation, type of lung involvement, frequency of primary bacteremia, or meningitis . Hospital-acquired pneumococcemia was significantly more frequent in immunocompromised patients (34.7% versus 6.8%, P<0.0001), and resistance to penicillin was also more common in pneumococcal strains isolated from these patients (37.5% versus 20%, P=0.0009) . Septic shock occurred more frequently in immunocompromised patients, although the overall and related mortality were not significantly different from those found in non-immunocompromised patients (33.3% versus 22.5%, P=0.07, and 28.9% versus 20.9%, P=0.7 respectively) . In the multivariate analysis, multilobar pneumonia (odds ratio (OR) 15.7; 95% CI 6.00-41.30; P<0.001), inadequate treatment (OR 12.20; 95% CI 4.10-37.20; P<0.001), obtundation (OR 5.80; 95% CI 2.20-15.00; P<0.001) and hospital-acquired bacteremia (OR 4.80; 95% CI 1.00-14.60; P<0.006) were associated with an increased risk of mortality in patients with pneumococcemia . Only multilobar pneumonia (OR 7.90; 95% CI 4.10-15.35; P<0.001) was significantly associated with an increased risk of mortality in immunocompromised patients . Patients with acute leukemia and lymphoma had a greater mortality rate than non-immunocompromised patients (53.8% related mortality, P=0.05) . Analysis of these patients showed frequent inadequate empirical therapy with ceftazidime plus amikacin in the presence of beta-lactam resistance . CONCLUSIONS: Much of the burden of pneumococcal bacteremia was attributable to immunosuppressive diseases . In immunocompromised patients, pneumococcemia was frequently acquired within the hospital during the treatment of the underlying condition, and resistance to penicillin was common . Patients with acute leukemia and lymphoma who develop fever and pneumonia should be treated with drugs active against beta-lactam-resistant pneumococci, irrespective of the setting in which the infection develops.

Int J Infect Dis, 2003 Mar, 7(1), 29 - 35
Serotypes of respiratory tract isolates of Streptococcus pneumoniae from Jamaican children; Allen UD et al.; BACKGROUND: Data are lacking on the pneumococcal serotypes present in many developing regions, including the Caribbean . We examined the serotypes of nasopharyngeal (NP) isolates of pneumococci obtained from Jamaican children . METHODS: We obtained NP samples from children seen in the Emergency Department at the Bustamante Children's Hospital . The samples were transported to Canada for isolation and serotyping of pneumococci . RESULTS: We obtained 94 isolates from 276 children; median age 3.4 years . The majority (57%) had symptoms of acute respiratory infection at the time of sampling . The main serotypes carried were 6B (20.5%), 19F (14.5%), and 14 (8.4%) . Non-typable isolates accounted for 10.8% of the isolates . Fifty-nine per cent of the serotypes were present among the 11 being considered for candidate pneumococcal conjugate vaccines (95% CI 48-70%); the corresponding proportion present in the recently licensed 7-valent vaccine was 57% (95% CI 45-67%) . A significant proportion of the serotypes found is absent from those to be included in future conjugate vaccines (P<0.0001; reference=85% expected serotype representation) . Less than 5% of isolates were non-susceptible to penicillin (3.2%), cefotaxime-ceftriaxone (3.2%) and cefuroxime (3.2%), while 8.4% and 1.l% of isolates were resistant to trimethoprim-sulfamethoxazole and erythromycin respectively . There were three isolates with resistance to two or more classes of drug . These isolates were all resistant to penicillin (MIC 2 micro g/mL); the serotypes were 14, 23F, and 19F . CONCLUSION: A significant proportion of the serotypes found is absent from those to be included in future conjugate vaccines.

J Infect Dis, 2003 May 1, 187(9), 1424 - 32 Epub 2003 Apr 04.
Clonal relationships between invasive and carriage Streptococcus pneumoniae and serotype- and clone-specific differences in invasive disease potential; Brueggemann AB et al.; By use of multilocus sequence typing, Streptococcus pneumoniae isolates causing invasive disease (n=150) were compared with those from nasopharyngeal carriage (n=351) among children in Oxford . The prevalence of individual clones (sequence types) and serotypes among isolates from invasive disease was related to their prevalence in carriage, and an odds ratio (OR) for invasive disease was calculated for the major clones and serotypes . All major carried clones and serotypes caused invasive disease, although their ability to do so varied greatly . Thus, 2 serotype 14 clones were approximately 10-fold overrepresented among disease isolates, compared with carriage isolates, whereas a serotype 3 clone was approximately 10-fold underrepresented . The lack of heterogeneity between the ORs of different clones of the same serotype, and analysis of isolates of the same genotype, but different serotype, suggested that capsular serotype may be more important than genotype in the ability of pneumococci to cause invasive disease.

J Infect Dis, 2003 May 1, 187(9), 1411 - 5 Epub 2003 Apr 15.
Matrix metalloproteinase-9 in pneumococcal meningitis: activation via an oxidative pathway; Meli DN et al.; In experimental bacterial meningitis, matrix metalloproteinases (MMPs) and reactive oxygen species (ROS) contribute to brain damage . MMP-9 increases in cerebrospinal fluid (CSF) during bacterial meningitis and is associated with the brain damage that is a consequence of the disease . This study assesses the origin of MMP-9 in bacterial meningitis and how ROS modulate its activity . Rat brain-slice cultures and rat polymorphonuclear cells (PMNs) that had been challenged with capsule-deficient heat-inactivated Streptococcus pneumoniae R6 (hiR6) released MMP-9 . Coincubation with either catalase, with the myeloperoxidase inhibitor azide, or with the hypochlorous acid scavenger methionine almost completely prevented activation, but not the release, of MMP-9, in supernatants of human PMNs stimulated with hiR6 . Thus, in bacterial meningitis, both brain-resident cells and invading PMNs may act as sources of MMP-9, and stimulated PMNs may activate MMP-9 via an ROS-dependent pathway . MMP-9 activation by ROS may represent a target for therapeutic intervention in bacterial meningitis.

J Gynecol Obstet Biol Reprod (Paris), 2003 Apr, 32(2), 132 - 8
{Risk factors and screening strategy for group B streptococcal colonization in pregnant women: results of a prospective study}; Jaureguy F et al.; OBJECTIVES: Group B Streptococcus (GBS) continues to be the most important bacterial cause of sepsis, meningitidis in newborns . American consensus guidelines have been published . They recommended the use of either risk-based strategy or screening-based approach for GBS colonization in pregnant women to identify candidates for intrapartum prophylaxis . Screening consists of obtaining vaginal and anorectal specimens for culture at 35 to 37 weeks' gestation . The aim of this prospective study was to assess the usefulness of systematic and concomitant GBS screening by rectal and vaginal swab in pregnant women . A questionnaire designed to determine the risk factors for colonization by GBS was completed . MATERIALS AND METHODS: We have screened 370 pregnant women with rectal and vaginal swab . RESULTS: Fifty seven (15.4%) women had positive GBS cultures . Of those women, the rectum and the vagina were the only site of colonization in 16 (4.3%) and 8 (2.2%) women respectively . None of the factors studied was significantly associated with GBS colonization . CONCLUSION: Detection of GBS is enhanced by 40% by using vaginal and anorectal swabs compared to a vaginal swab alone . No studied factor appeared to predict GBS colonization, which incited us to screen all pregnant women.

Arch Dis Child, 2003 May, 88(5), 438 - 43
Causes and outcome of young infant admissions to a Kenyan district hospital; English M et al.; AIMS: To provide a comprehensive description of young infant admissions to a first referral level health facility in Kenya . These data, currently lacking, are important given present efforts to standardise their care through the integrated management of childhood illness (IMCI) and for prioritising both health care provision and disease prevention strategies . METHODS: Prospective, 18 month observational study in a Kenyan district hospital of all admissions less than 3 months of age to the paediatric ward . RESULTS: A total of 1080 infants were studied . Mortality was 18% overall, though in those aged 0-7 days it was 34% . Within two months of discharge a further 5% of infants aged <60 days on admission had died . Severe infection and prematurity together accounted for 57% of inpatient deaths in those aged <60 days, while jaundice and tetanus accounted for another 27% . S pneumoniae, group B streptococcus, E coli, and Klebsiella spp . were the most common causes of invasive bacterial disease . Hypoxaemia, hypoglycaemia, and an inability to feed were each present in more than 20% of infants aged 0-7 days . Both hypoxaemia and the inability to feed were associated with inpatient death (OR 3.8 (95% CI 2.5 to 5.8) and 7.4 (95% CI 4.8 to 11.2) respectively) . CONCLUSIONS: Young infants contribute substantially to paediatric inpatient mortality at the first referral level, highlighting the need both for basic supportive care facilities and improved disease prevention strategies.

Clin Infect Dis, 2003 May 1, 36(9), 1132 - 8 Epub 2003 Apr 22.
Streptococcus pneumoniae bacteremia: duration of previous antibiotic use and association with penicillin resistance; Ruhe JJ et al.; Previous antibiotic exposure is one of the most important predictors for acquisition of penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) infection . To determine the impact of duration of exposure to different antibiotic classes, a study of 303 patients with S . pneumoniae bacteremia was undertaken . Ninety-eight cases of bacteremia (32%) were caused by a penicillin-nonsusceptible isolate . Bivariate analysis revealed that use of beta-lactams, sulfonamides, and macrolides within the last 1 and 6 months before presentation was associated with PNSP bacteremia (P<.05) . Fluoroquinolone consumption was not related to bacteremia due to PNSP (P>.1) . Both short- and long-term beta-lactam use significantly increased the risk for PNSP infection . Logistic regression analysis revealed that use of beta-lactams and macrolides in the 6 months before the first positive blood culture result were independent risk factors (P<.05) . Risk for acquiring PNSP infection depends on both the class of antibiotic to which the patient was exposed and the duration of therapy.

Presse Med, 2003 Apr 5, 32(13 Pt 1), 599 - 601
{Streptococcus suis bacteremia}; Pedroli S et al.; INTRODUCTION: Streptococcus suis infection is recognised despite it rareness as a zoonotic occupational disease in humans, and is often associated with meningitis, more rarely with bacteremia . OBSERVATION: A Streptococcus suis bacteremia occurred in a hunter and was complicated by septic shock with disseminated intravascular coagulation, rhabdomyolysis and purpura fulminans . Contamination had occurred through inoculation of a cut on the thumb when the hunter was slaughtering a wild boar . The blood cultures isolated Streptococcus suis . The patient died 36 hours after admission, despite intensive care and adapted antibiotic treatment with penicillin A and macrolide . CONCLUSION: Streptococcus suis bacteremia are uncommon but serious in humans . Despite adapted treatment, evolution may be fatal, so their conditions of occurrence must be well known by hunters and practitioners.

Chemotherapy, 2003 May, 49(1-2), 56 - 61
Detection of macrolide resistance in Streptococcus pneumoniae; Kimura T et al.; We determined the susceptibilities of recent clinical isolates of Streptococcus pneumoniae to 19 antibiotics . The frequency of erythromycin nonsusceptibility was high, i.e . 8/13 (61.5%), 10/14 (71.4%) and 11/11 isolates (100%) from 13 penicillin-susceptible, 14 penicillin-intermediate and 11 penicillin-resistant S . pneumoniae, respectively . Macrolide resistance was detected by polymerase chain reaction (PCR) and disk diffusion methods . Of these erythromycin-nonsusceptible pneumococcal isolates, 13/29 (44.8%) isolates contained genomic copies of MEFA and showed non-'D'-shaped zones of inhibition observed around rokitamycin and/or clindamycin disks . Sixteen out of 29 isolates (55.2%) contained copies of ERMB and showed typical 'D'-shaped zones of inhibition, except one isolate . Although the macrolide resistance determinants, MEFA and ERMB, could be identified by PCR and disk diffusion methods, PCR methods were more reliable in elucidating these determinants . The susceptibility pattern to 14-, 15- and 16-membered macrolides and clindamycin differed between the MEFA+ and ERMB+ isolates . All isolates were susceptible to levofloxacin, sparfloxacin and vancomycin . The MICs of sitafloxacin were lowest among the fluoroquinolones examined for 38 isolates .

J Periodontol, 2003 Mar, 74(3), 312 - 22
Can toothpaste or a toothbrush with antibacterial tufts prevent toothbrush contamination?
Quirynen M, De Soete M, Pauwels M, Gizani S, Van Meerbeek B, van Steenberghe D.
BACKGROUND: Periopathogens and cariogenic species survive more than 48 hours on toothbrushes even under dry storage . This study examined a decontamination of toothbrushes by means of the bactericidal effect of different toothpastes or a special coating of the tufts . METHODS: Eight untreated periodontitis patients were professionally brushed, using a new toothbrush per quadrant and 3 different toothpastes containing either amine/stannous fluoride (AmF/SnF2), amine fluoride (AmF), or a mild surfactant as major antibacterial component (excipient), or no paste (C) . The brushes were rinsed and stored dry at room temperature . At different time intervals, 4 tufts per toothbrush were processed for selective and non-selective culturing procedures . The protocol was repeated comparing AmF/SnF2 and C with 2 toothbrushes with coated tufts (coat1 and coat2) . RESULTS: At baseline, C brushes (n = 16) harbored 10(7), 10(8), and 10(6) colony forming units (CFU) of aerobic, anaerobic, and black pigmented species, respectively . After 24 hours 10(6) CFU of aerobic and anaerobic species could still be cultured from 14 of the 16 brushes . Black-pigmented species remained detectable up to 4 hours; detection frequencies for Fusobacterium nucleatum and Streptococcus mutans at 24 hours were 5/16 . With AmF/SnF2 and AmF toothpaste the number of adhering bacteria was already 2 log lower at baseline (P<0.05), but not for the excipient (0.5 log, P = 0.7) . With AmF/SnF2 no vital species could be detected after 8 hours . AmF reduced the bacterial survival rate significantly more than the excipient, but less than AmF/SnF2 (P<0.05) . The bactericidal effect of coat1 and coat2 was negligible when compared to C (P>0.20), and clearly inferior to the AmF/SnF2 paste (P<0.0001) . After 24 hours these brushes still harbored >10(5) CFU . CONCLUSIONS: Toothpastes can significantly reduce contamination of toothbrushes, but their bactericidal activity is dependent on their composition . Coated tufts failed to limit the bacterial contamination.

Indian J Med Res, 2002 Nov, 116, 177 - 85
Epidemiological typing of Streptococcus pneumoniae from various sources in India & Korea using Box A PCR fingerprinting; Lalitha MK et al.; BACKGROUND & OBJECTIVES: Epidemiological typing of Streptococcus pneumoniae is necessary to study genetic relatedness among strains . The Box A PCR assay, a good epidemiological tool for high resolution typing of pneumococcal isolates, was used for comparison of strains of S . pneumoniae from Korea, an area of high penicillin resistance and India with low resistance to penicillin . METHODS: The pneumococcal strains from Indian and Korean sources included in the study belonged to serotypes 19F, 23F, 6A & 6B . The penicillin susceptibility of the strains was confirmed by determination of minimum inhibitory concentration values . The strains were then fingerprinted using the Box A PCR protocol and the results were further analysed by Molecular Analyst Software . RESULTS: The Box fingerprinting technique produced sharp, clear and reproducible banding patterns for strains of S . pneumoniae included in the study . There was no similarity between Indian and Korean strains at the genetic level . Among the Korean strains with similar serotypes, the level of similarity varied . Except for one pair (serotype 23F), that showed a level of homology of about 90 per cent, almost all the others showed less than 80 per cent homology . It was also seen that there was a high percentage of homology (> 90% in nasopharyngeal isolates from India belonging to serotype 19F) between isolates from similar source . Comparison of the Indian and Korean isolates of similar serotype showed low homology, except for one cluster of two strains with serotype 6B which showed 84 per cent homology (blood isolates from India and Korea) . INTERPRETATION & CONCLUSION: Box A PCR is a highly discriminatory and useful method for typing S . pneumoniae . The results of the study have shown low levels of homology between strains from within India and also between two geographically distinct areas.

Gastrointest Endosc, 2003 May, 57(6), 672 - 8
Prospective risk assessment of bacteremia and other infectious complications in patients undergoing EUS-guided FNA; Levy MJ et al.; BACKGROUND: There are few data regarding the risk of bacteremia with EUS-guided FNA . This study prospectively evaluated the frequency of bacteremia and other infectious complications after EUS-guided FNA . METHODS: Patients referred for EUS-guided FNA of the upper GI tract lesions were considered for enrollment . Patients were excluded if there was an indication for preprocedure administration of antibiotics based on ASGE guidelines, had taken antibiotics within the prior 7 days, or if they had a pancreatic cystic lesion . Blood cultures were obtained immediately before the procedure, after routine endoscopy/radial EUS, and 15 minutes after EUS-guided FNA . RESULTS: Fifty-two patients underwent EUS-guided FNA at 74 sites (mean 1.4 sites/patient) totaling 266 passes of the fine needle (mean 5.1 FNA/patient) . Coagulase negative Staphylococcus was grown in cultures from 3 patients (5.8%; 95% CI {1%, 15%}) and was considered a contaminant . Three patients (5.8%; 95% CI {1%, 15%}) developed bacteremia: Streptococcus viridans (n = 2), unidentified gram-negative bacillus (n = 1) . No signs or symptoms of infection developed in any patient . CONCLUSION: EUS-guided FNA of solid lesions in the upper GI tract should be considered a low-risk procedure for infectious complications that does not warrant prophylactic administration of antibiotics for prevention of bacterial endocarditis.

Antimicrob Agents Chemother, 2003 May, 47(5), 1689 - 93
Baseline study to determine in vitro activities of daptomycin against gram-positive pathogens isolated in the United States in 2000-2001; Critchley IA et al.; The activity of daptomycin was assessed by using 6,973 gram-positive bacteria isolated at 50 United States hospitals in 2000 and 2001 . Among the isolates of Streptococcus pneumoniae (n = 1,163) collected, the rate of penicillin resistance was 16.1%; rates of oxacillin resistance among Staphylococcus aureus isolates (n = 1,018) and vancomycin resistance among Enterococcus faecium isolates (n = 368) were 30.0 and 59.5%, respectively . Multidrug-resistant (MDR) phenotypes (isolates resistant to three or more different chemical classes of antimicrobial agents) accounted for 14.2% of S . pneumoniae isolates, 27.1% of S . aureus isolates, and 58.4% of E . faecium isolates . For all gram-positive species tested, MICs at which 90% of the isolates tested were inhibited (MIC(90)s) and MIC ranges for directed-spectrum agents (daptomycin, quinupristin-dalfopristin, and linezolid) were identical or highly similar for isolates susceptible or resistant to other agents or MDR . Daptomycin had a MIC(90) of 0.12 micro g/ml for both penicillin-susceptible and -resistant isolates of S . pneumoniae . Against oxacillin-resistant S . aureus daptomycin had a MIC(90) of 0.5 micro g/ml, and it had a MIC(90) of 4 micro g/ml against both vancomycin-susceptible and -resistant E . faecium . The MIC(90)s for daptomycin and other directed-spectrum agents were unaffected by the regional or anatomical origin of isolates or patient demographic parameters (patient age, gender, and inpatient or outpatient care) . Our results confirm the gram-positive spectrum of activity of daptomycin and that its activity is independent of susceptibility or resistance to commonly prescribed and tested antimicrobial agents . This study may serve as a baseline to monitor future changes in the susceptibility of gram-positive species to daptomycin following its introduction into clinical use.

Antimicrob Agents Chemother, 2003 May, 47(5), 1630 - 5
Pharmacodynamics of a novel des-F(6)-quinolone, BMS-284756, against Streptococcus pneumoniae in the thigh infection model; Nicolau DP et al.; BMS-284756 is a novel quinolone that lacks the six-position fluorine typical of existing compounds . Despite this structural change, BMS-284756 maintains potent antibacterial activity against gram-negative and gram-positive aerobic and anaerobic pathogens . The objective of this study was to define the pharmacodynamic profile of BMS-284756 against Streptococcus pneumoniae . Protein binding in mice was assessed by the ultrafiltration method . For pharmacodynamic studies, neutropenic ICR mice were used, as well as an immunocompetent mouse species, CBA/J, in order to evaluate the impact of white blood cells on infection outcome . Mice were infected with 10(5) to 10(6) CFU per thigh, and therapy was initiated after 2 h . Animals received BMS-284756 orally over a range of 1.25 to 100 mg/kg/day divided into one to four doses . At 0 and 24 h postinfection, thighs were harvested for bacterial density measurement . Survival was assessed during 96 h of therapy and again at 3 days after therapy . Pharmacokinetic studies were also conducted with infected mice . Protein binding was determined to be 80% . The MICs for clinical isolates (n = 8) ranged from 0.03 to 2 micro g/ml . The change in bacterial density and survival was correlated with the pharmacodynamic parameters percentage of time that the drug concentration in serum remains above the MIC, AUC (area under the concentration-time curve)/MIC ratio, and peak/MIC ratio, and the best predictor of response was the AUC/MIC ratio for both outcome measures . Total AUC/MIC ratios of 100 to 200 appear to result in maximal bactericidal effects . While a total AUC/MIC ratio exposure value of 100 (free AUC/MIC ratio, approximately 20) resulted in nearly 100% survival at the conclusion of therapy, a total AUC/MIC ratio of 200 (free AUC/MIC ratio, approximately 40) was required to ensure survival at 3 days posttherapy . These data demonstrate (i) the in vivo bactericidal activity of BMS-284756 against S . pneumoniae, (ii) that protein binding has a profound impact on the in vivo pharmacodynamic assessment of BMS-284756, and (iii) that an AUC/MIC ratio of 200 (free AUC/MIC ratio, approximately 40) appears to best characterize the required dynamic exposure for optimization of bactericidal activity and maximal survival.

Int J Dermatol, 2003 Feb, 42(2), 110 - 5
IgG class antibodies to heat shock-induced streptococcal antigens in psoriatic patients; Perez-Lorenzo R et al.; BACKGROUND: Psoriasis is a chronic inflammatory skin disease . Probably autoimmune in nature, and associated with streptococcal throat infections as a triggering factor . Although many groups have associated the disease with other pathogens, Streptococcus pyogenes seems to be the most important microorganism related to this disease . Therefore, it is necessary to identify the streptococcal antigens involved in the process . METHODS: In this work IgG class antibodies to soluble antigens obtained from Staphyloccus aureus, Candica albicans or S . pyogenes before and after heat shock induction, were analyzed by ELISA in 28 psoriatic patients and 30 healthy donors . RESULTS: In all cases, the patients and the controls had IgG class antibodies to the four antigens . Nevertheless, the IgG levels to the heat shock-induced S . pyognes were statistically different between the patients and the controls (P < 0.001) . There was no difference between the groups when the IgG antibodies to the other antigens, including the noninduced streptococcal extract, were analyzed . Additionally, anti-streptolysin O titers and throat cultures were carried out in all patients and controls . No differences between ASO titers were found but the patients were more frequently colonized by pyogenes . CONCLUSION: Results obtained in this study suggest that heat shock-induced proteins from S . pyogenes are associated with psoriasis.

Rev Med Chil, 2003 Feb, 131(2), 145 - 54
{Molecular epidemiology of a streptococcus pyogenes related nosocomial outbreak in a burn unit}; Fica A et al.; BACKGROUND: Group A Streptococcal (GAS) infections have increased in frequency and severity worldwide . During April 1996, a nosocomial outbreak associated to GAS infections affected seven patients admitted to a pediatric burn unit . The causative organism was likely disseminated from the source patient to another child in the emergency room before he was transferred to the burn unit . Patients developed burn infections or invasive disease . One of them died due to a toxic shock syndrome and 3 other lost their skin grafts . Perineal and nasal microbiological surveillance of 42 related health care workers identified only one of them as carrier of S pyogenes . AIM: To report a molecular analysis of an apparently clonal outbreak . MATERIAL AND METHODS: The available isolates were analyzed by molecular methods including random amplified polymorphic DNA analysis (RAPD) with 4 different primers, Sma-I pulsed field gel electrophoresis (PFGE) analysis, and speA, speB and speC detection by polymerase chain reaction (PCR) . RESULTS: Two phylogenetically distant and sequentially isolated bacterial groups were identified either by RAPD analysis with selected primers or by Smal-PFGE analysis . The first group involved isolates identified in two patients that included the lethal case . The second bacterial group comprised 5 clinical isolates and the perineal and nasal isolates obtained from a health care worker . Only strains belonging to the first group harbored the speA gene and were associated with invasive disease . The second group could be split further in two subgroups according to their speB profile . CONCLUSIONS: RAPD analysis with selected primers can reproduce the PFGE-discriminating ability on the epidemiological analysis of GAS infections.

Kansenshogaku Zasshi, 2003 Mar, 77(3), 133 - 7
{Mutations of gyrA gene and parC gene in Streptococcus pneumoniae}; Miyamoto H et al.; Fifty-six levofloxacin-susceptible strains of Streptococcus pneumoniae were isolated from various clinical material in July, 2002 from June, 2001, examined antimicrobial susceptibility testing of levofloxacin and sparfloxacin, and performed analysis of gyrA gene and parC gene . 56 strains were not sparfloxacin-resistance . There was not found to mutation of gyrA gene . However, the individual mutations of parC gene were accepted by 13 strains among 56 strains which showed sensitivity by levofloxacin . One strain was Asp-78-->Asn, other one strain was Ser-79-->Phe, and 11 strains were Lys-137-->Asn . These results suggest that fluoroquinolone-resistance could be due to the multiple mutations in gyrA gene and parC gene, although the individual mutation of parC gene existed also in levofloxacin-susceptible strains.

Infez Med, 2000, 1(8), 34 - 38
{In vitro susceptibility of different erythromycin-resistant phenotypes of Streptococcus pyogenes to moxifloxacin and other fluoroquinolones}; Novielllo S et al.; The aim of the present study was to evaluate the in vitro activity of moxifloxacin (BAY 12-8039) compared with ciprofloxacin, ofloxacin and sparfloxacin against 156 Group A beta-haemolytic Streptococcus (GABHS) strains . Sixty strains were macrolide- lincosamide- and streptogramin B susceptible; 16 strains exhibited a constitutive resistance phenotype; 32 strains exhibited an inducible phenotype; and 48 strains were characterized by the M-type efflux-dependent phenotype . The MICs were determined by an agar dilution method according to NCCLS-approved guidelines . Moxifloxacin showed an enhanced activity compared with the other fluoroquinolones against all the different macrolide-resistant phenotypes.

J Immunol, 2003 May 1, 170(9), 4724 - 30
IL-1 receptor type 1 gene-deficient mice demonstrate an impaired host defense against pneumococcal meningitis; Zwijnenburg PJ et al.; The fatality rate associated with Streptococcus pneumoniae meningitis remains high despite adequate antibiotic treatment . IL-1 is an important proinflammatory cytokine, which is up-regulated in brain tissue after the induction of meningitis . To determine the role of IL-1 in pneumococcal meningitis we induced meningitis by intranasal inoculation with 8 x 10(4) CFU of S . pneumoniae and 180 U of hyaluronidase in IL-1R type I gene-deficient (IL-1R(-/-)) mice and wild-type mice . Meningitis resulted in elevated IL-1alpha and IL-1beta mRNA and protein levels in the brain . The absence of an intact IL-1 signal was associated with a higher susceptibility to develop meningitis . Furthermore, the lack of IL-1 impaired bacterial clearance, as reflected by an increased number of CFU in cerebrospinal fluid of IL-1R(-/-) mice . The characteristic pleocytosis of meningitis was not significantly altered in IL-1R(-/-) mice, but meningitis was associated with lower brain levels of cytokines . The mortality was significantly higher and earlier in the course of the disease in IL-1R(-/-) mice . These results demonstrate that endogenous IL-1 is required for an adequate host defense in pneumococcal meningitis.

Arch Dermatol, 2003 Apr, 139(4), 467 - 71
Effect of antibiotics on the oropharyngeal flora in patients with acne; Levy RM et al.; OBJECTIVE: To estimate the prevalence and resistance patterns of Streptococcus pyogenes and Staphylococcus aureus in the oropharynx of individuals with acne who were using or not using antibiotic therapy . DESIGN: A cross-sectional study . SETTING: The Dermatology Department of the Hospital of the University of Pennsylvania, Philadelphia . PATIENTS: Patients with acne . MAIN OUTCOME MEASURES: Presence or absence of S pyogenes and S aureus in the oropharynx as determined by culture and their resistance patterns to tetracycline antibiotics as determined by agar disk diffusion . RESULTS: Of 105 patients who participated, 42 were using oral or topical antibiotics and 63 patients were not using antibiotics . Six (10%) of those 63 not using any antibiotics had positive S pyogenes cultures compared with 13 (33%) of those successfully evaluated using antibiotics (n = 39) (prevalence risk ratio, 3.5; 95% confidence interval, 1.4-8.6; P=.003) . A total of 85% of S pyogenes cultures (11/13) from those using antibiotics were resistant to at least 1 tetracycline antibiotic compared with 20% (1/5) from those not using antibiotics (P=.01) . Of those not using antibiotics, 29% (18/62) had positive S aureus cultures compared with 22% (9/41) of those using antibiotics (prevalence risk ratio, 0.76; 95% confidence interval, 0.38-1.5; P=.42) . No significant differences in resistance patterns of S aureus were found . CONCLUSIONS: Streptococcus pyogenes colonization and resistance in the oropharynx are associated with antibiotic therapy in patients with acne . The clinical and long-term effects of this finding need to be studied further.

Vaccine, 2003 May 16, 21(17-18), 2093 - 6
Invasive pneumococcal diseases in Uruguayan children: comparison between serotype distribution and conjugate vaccine formulations; Camou T et al.; An on-going Streptococcus pneumoniae surveillance in Uruguay furnished national information on serotype distribution of isolates from invasive infections in children </=5 years . The adequacy of 7-, 9- and 11-valent conjugate vaccine formulations was evaluated, in comparison with the prevalence of the serotypes causing disease in this target population . From 1994 to 2001, 506 isolates were submitted to the National Reference Laboratory . The heptavalent vaccine would cover 49% of the invasive isolates, while the nonavalent vaccine would potentially prevent 76% of cases . The 11-valent vaccine would increase coverage to 86% . All the serotype/groups of penicillin-resistant isolates are included in the three conjugate vaccine formulations . The available data indicate that the 9- or the 11-valent vaccines, if affordable, are the most suitable formulations for Uruguayan children.

Vaccine, 2003 May 16, 21(17-18), 1958 - 64
Stimulation of long-lasting protection against Streptococcus pyogenes after intranasal vaccination with non adjuvanted fibronectin-binding domain of the SfbI protein; Schulze K et al.; Protective immunity against Streptococcus pyogenes can be induced by intranasal vaccination with the fibronectin-binding domain (H12 fragment) of the fibronectin-binding protein I (SfbI) co-administered with the B subunit of the cholera toxin (CTB) as mucosal adjuvant . However, intranasal administration of A-B moiety bacterial toxins or their derivatives has been associated with potentially severe side effects . Since the SfbI protein exhibits adjuvant properties, we investigated whether vaccination with the H12 fragment alone is sufficient to promote long-lasting protection . The obtained results demonstrated that the humoral and cellular immune responses stimulated at both systemic and mucosal levels were almost identical when mice were vaccinated with the H12 fragment in the presence or absence of CTB . Immunized mice were protected against challenge with a lethal dose of S . pyogenes given 36 or 110 days after primary vaccination to the same extent (80% survival), regardless of CTB incorporation . These results demonstrate that vaccination with the H12 fragment stimulates long-lasting protective immunity . The adjuvant properties exhibited by the fibronectin-binding domain of the SfbI protein strength the potential of this antigen for inclusion in multi-component vaccines against S . pyogenes.

Vaccine, 2003 May 16, 21(17-18), 1815 - 25
The potential indirect effect of conjugate pneumococcal vaccines; O'Brien KL et al.; Pneumococcal conjugate vaccines are highly effective in preventing invasive disease in infants and young children, with favorable safety and immunogenicity profiles . These pediatric vaccines have also shown efficacy in reducing cases of non-invasive disease (i.e . otitis media, pneumonia) . Recently, pneumococcal conjugate vaccines have demonstrated additional protective qualities that may enhance their use worldwide . For example, they can reduce nasopharyngeal acquisition of vaccine-specific serotypes of Streptococcus pneumoniae, which may in turn reduce the incidence of pneumococcal disease among non-vaccinated individuals; this is termed indirect or herd immunity . Although the emergence of antibiotic-resistant strains has complicated disease management, pneumococcal conjugate vaccines have been shown to protect against pneumococcal disease caused by such strains because most antibiotic-resistant strains are of the serotypes included in these vaccines . Thus, widespread use of these conjugate vaccines may prevent disease by providing both direct and indirect immunity, and may reduce the use of antibiotics and the development of antibiotic resistance worldwide.

Microb Drug Resist, 2003 Spring, 9(1), 81 - 6
Identification of multidrug-resistant Streptococcus pneumoniae strains isolated in Poland by multilocus sequence typing; Sadowy E et al.; Multilocus sequence typing (MLST) of 35 isolates of multidrug-resistant Streptococcus pneumoniae recovered in Poland during 1995-1996 distinguished 10 different sequence types (ST) . The majority of the isolates were assigned to two Polish clones of serotypes 6B and 23F, although the international clones, Spain23F-1 and Spain9V-3, were also identified . Similar results were obtained using pulsed-field gel electrophoresis (PFGE), providing a direct comparison of these two typing methods.

Microb Drug Resist, 2003 Spring, 9(1), 73 - 80
Macrolide resistance in Streptococcus pneumoniae isolated from patients with community-acquired lower respiratory tract infections in Portugal: results of a 3-year (1999-2001) multicenter surveillance study; Melo-Cristino J et al.; A nationwide multicenter study (including 31 laboratories) of the antimicrobial susceptibility of 1210 Streptococcus pneumoniae isolates from patients with community-acquired lower respiratory tract infections (LRTI) was carried out over 3 years (1999-2001) in Portugal . Testing of all isolates was undertaken in a central laboratory . Overall macrolide resistance was 13.1% . Decreased susceptibility to penicillin was 24.5% (15.5% low-level and 9.0% high-level resistance) . Taken into consideration, the resistance rates reported in a previous surveillance study of 1989-1993, a six-fold increase of erythromycin resistance in the last decade was documented . Resistance to erythromycin, clarithromycin, and azithromycin was higher in pediatric patients than in adults . The overwhelming majority (82.3%) of macrolide-resistant isolates were multidrug resistant, although 44.9% were fully susceptible to penicillin . Most macrolide-resistant isolates (80.4%) showed the MLSB phenotype (76.6% MLSB-constitutive resistance, and 3.8% MLSB-inducible resistance) and were also resistant to clindamycin, tetracycline, and co-trimoxazole . The M phenotype was seen in 19.6% isolates and these had MIC90 values of 8 mg/L for erythromycin and clarithromycin, and of 12 mg/L for azithromycin . The clinical significance of macrolide resistance in the management of LRTI is discussed . Because of the specific situation concerning macrolide resistance described in S . pneumoniae, careful use of macrolide antibiotics in therapy and cautious monitoring of macrolide resistance should be continued in Portugal.

Microb Drug Resist, 2003 Spring, 9(1), 17 - 24
Fluoroquinolone resistance in Streptococcus pneumoniae: evidence that gyrA mutations arise at a lower rate and that mutation in gyrA or parC predisposes to further mutation; Gillespie SH et al.; Fluoroquinolones are being increasingly used for acute lower respiratory tract infection where Streptococcus pneumoniae is the most important bacterial pathogen . S . pneumoniae becomes resistant to quinolone antibiotics by mutations in a small section of the parC and gyrA genes . In this study, we investigated the mutation rates and spectrum of resistance when ciprofloxacin and gemifloxacin were the selective agents . When ciprofloxacin was the selective agent, parC mutants arose at a rate of 1.1 x 10(-9) mutations per cell division . There were two double mutants: parC + gyrA and parC + gyrB, and these mutations arose in as few as five generations . When gemifloxacin was the selective agent, all but one of the colonies growing on the x2 MIC plate had no mutations in gyrA or parC . The only mutation identified was in gyrA, and it appeared at a rate of 1.6 x 10(-11) . When the gemifloxacin MIC of strains with mutations in parC was determined, there was no change from the susceptible parent . These data indicate that S . pneumoniae becomes resistant to gemifloxacin through mutation in gyrA rather than parC . Because gyrA mutations arise at a lower rate than parC mutations, it is likely that resistance to gemifloxacin will emerge more slowly than is seen with those quinolones that become resistant through an initial mutation in parC . The rate at which second-step mutants emerged was 1.3 x 10(-8) for parC Serine 79 Tyrosine and 7.2 x 10(-9) for gyrA Serine 81 Phenylalanine, 12 and 450 times higher, respectively, than for first-step rates, suggesting that mutation in either gene readies the genome for further mutation.

Microb Drug Resist, 2003 Spring, 9(1), 7 - 15
VO1, a temperate bacteriophage of the type 19A multiresistant epidemic 8249 strain of Streptococcus pneumoniae: analysis of variability of lytic and putative C5 methyltransferase genes; Obregon V et al.; A temperate bacteriophage (VO1) has been isolated from the Streptococcus pneumoniae type 19F multiresistant epidemic 8249 strain (South African strain) . Structural analysis of the specific integration site, protein composition, restriction patterns, and molecular dissection of the lytic system of this phage revealed high sequence similarity with MM1, a temperate phage from the Spain23F-1 strain of pneumococcus, another multiresistant epidemic clone . The different pneumococcal strains sequenced so far exhibit an identical and single attB located in the same site of the genome . Remarkably, the LytA amidase coded by VO1 showed clear differences with that of the host bacterium in contrast with the situation previously documented for bacterial- and phage-coded amidases of pneumococcus . In addition, a new gene (orfmet) putatively coding for a C5 methyltransferase has been identified . A noticeable variability affecting the presence (or absence) of this supernumerary gene(s) in the same region of the genomes of three otherwise highly similar phages (i.e., VO1, MM1, and HB-3) suggests frequent recombinational events leading to introduce variability in this genome region . The peculiarities of genes like lytA and orfmet in VO1 provide interesting insights on mechanisms of horizontal transfer and lysogenic state co-evolution.

Infect Immun, 2003 May, 71(5), 2881 - 4
Histidine and aspartic acid residues important for immunoglobulin G endopeptidase activity of the group A Streptococcus opsonophagocytosis-inhibiting Mac protein; Lei B et al.; The secreted Mac protein made by serotype M1 group A Streptococcus (GAS) (designated Mac(5005)) inhibits opsonophagocytosis and killing of GAS by human polymorphonuclear neutrophils . This protein also has cysteine endopeptidase activity against human immunoglobulin G (IgG) . Site-directed mutagenesis was used to identify histidine and aspartic acid residues important for Mac IgG endopeptidase activity . Replacement of His262 with Ala abolished Mac5005 IgG endopeptidase activity . Asp284Ala and Asp286Ala mutant proteins had compromised enzymatic activity, whereas 21 other Asp-to-Ala mutant proteins cleaved human IgG at the apparent wild-type level . The results suggest that His262 is an active-site residue and that Asp284 and Asp286 are important for the enzymatic activity or structure of Mac protein . These Mac mutants provide new information about structure-activity relationships in this protein and will assist study of the mechanism of inhibition of opsonophagocytosis and killing of GAS by Mac.

Infect Immun, 2003 May, 71(5), 2758 - 65
Inactivation of the srtA gene affects localization of surface proteins and decreases adhesion of Streptococcus pneumoniae to human pharyngeal cells in vitro; Kharat AS et al.; Inactivation of sortase gene srtA in Streptococcus pneumoniae strain R6 caused the release of beta-galactosidase and neuraminidase A (NanA) from the cell wall into the surrounding medium . Both of these surface proteins contain the LPXTG motif in the C-terminal domain . Complementation with plasmid-borne srtA reversed protein release . Deletion of murM, a gene involved in the branching of pneumococcal peptidoglycan, also caused partial release of beta-galactosidase, suggesting preferential attachment of the protein to branched muropeptides in the cell wall . Inactivation of srtA caused decreased adherence to human pharyngeal cells in vitro but had no effect on the virulence of a capsular type III strain of S . pneumoniae in the mouse intraperitoneal model . The observations suggest that--as in other gram-positive bacteria--sortase-dependent display of proteins occurs in S . pneumoniae and that some of these proteins may be involved in colonization of the human host.

Infect Immun, 2003 May, 71(5), 2656 - 64
MtsABC is important for manganese and iron transport, oxidative stress resistance, and virulence of Streptococcus pyogenes; Janulczyk R et al.; MtsABC is a Streptococcus pyogenes ABC transporter which was previously shown to be involved in iron and zinc accumulation . In this study, we showed that an mtsABC mutant has impaired growth, particularly in a metal-depleted medium and an aerobic environment . In metal-depleted medium, growth was restored by the addition of 10 microM MnCl(2), whereas other metals had modest or no effect . A characterization of metal radioisotope accumulation showed that manganese competes with iron accumulation in a dose-dependent manner . Conversely, iron competes with manganese accumulation but to a lesser extent . The mutant showed a pronounced reduction (>90%) of (54)Mn accumulation, showing that MtsABC is also involved in Mn transport . Using paraquat and hydrogen peroxide to induce oxidative stress, we show that the mutant has an increased susceptibility to reactive oxygen species . Moreover, activity of the manganese-cofactored superoxide dismutase in the mutant is reduced, probably as a consequence of reduced intracellular availability of manganese . The enzyme functionality was restored by manganese supplementation during growth . The mutant was also attenuated in virulence, as shown in animal experiments . These results emphasize the role of MtsABC and trace metals, especially manganese, for S . pyogenes growth, susceptibility to oxidative stress, and virulence.

Infect Immun, 2003 May, 71(5), 2615 - 25
RegR, a global LacI/GalR family regulator, modulates virulence and competence in Streptococcus pneumoniae; Chapuy-Regaud S et al.; The homolactic and catalase-deficient pathogen Streptococcus pneumoniae is not only tolerant to oxygen but requires the activity of its NADH oxidase, Nox, to develop optimal virulence and competence for genetic transformation . In this work, we show that the global regulator RegR is also involved in these traits . Genetic dissection revealed that RegR regulates competence and the expression of virulence factors, including hyaluronidase . In bacteria grown in vitro, RegR represses hyaluronidase . At neutral pH, it increases adherence to A549 epithelial cells, and at alkaline pH, it acts upstream of the CiaRH two-component signaling system to activate competence . These phenotypes are not associated with changes in antibiotic resistance, central metabolism, and carbohydrate utilization . Although the RegR(0) (where 0 indicates the loss of the protein) mutation is sufficient to attenuate experimental virulence of strain 23477 in mice, the introduction of an additional hyl(0) (where 0 indicates the loss of function) mutation in the RegR(0) strain 23302 dramatically reduces its virulence . This indicates that residual virulence of the RegR(0) Hyl(+) derivative is due to hyaluronidase and supports the dual role of RegR in virulence . This LacI/GalR regulator, not essential for in vitro growth in rich media, is indeed involved in the adaptive response of the pneumococcus via its control of competence, adherence, and virulence.

Infect Immun, 2003 May, 71(5), 2318 - 25
Trojan horse effect: phagocyte-mediated Streptococcus iniae infection of fish; Zlotkin A et al.; The salmonid macrophage-like cell line RTS-11 and purified trout pronephros phagocytes were used to analyze in vitro entry and survival of two Streptococcus iniae serotypes . Efficient invasion by S . iniae occurred in both cells, but only the type II strain persisted in pronephros phagocytes for at least 48 h . Ex vivo models of opsonin-dependent phagocytosis by pronephros phagocytes demonstrated increased phagocytosis efficacy . Analysis of phagocytes collected from diseased fish demonstrated that approximately 70% of the bacteria contained in the blood during the septic phase of the disease were located within phagocytes, suggesting an in vivo intracellular lifestyle . In addition to the augmented levels of bacteremia and enhanced survival within phagocytes, S . iniae type II induces considerable apoptosis of phagocytes . These variabilities in intramacrophage lifestyle might explain differences in the outcomes of infections caused by different serotypes . The generalized septic disease associated with serotype II strains is linked not only to the ability to enter and multiply within macrophages but also to the ability to cause considerable death of macrophages via apoptotic processes, leading to a highly virulent infection . We assume that the phenomenon of survival within phagocytes coupled to their apoptosis plays a crucial role in S . iniae infection . In addition, it may provide the pathogen an efficient mechanism of translocation into the central nervous system.

Tohoku J Exp Med, 2003 Mar, 199(3), 135 - 9
Nitric oxide metabolities in acute rheumatic fever; Narin F et al.; Acute rheumatic fever (ARF), is a systemic inflammatory disease etiologically related to infection with group A beta hemolytic streptococcus, characterized by a broad spectrum of disorders in cellular immunity . To estimate the activity of the immunopathological process in patients with ARF, plasma nitric oxide metabolities (NOx) concentrations, IL-1alpha and IL-2 levels were investigated in 22 patients with ARF at the time on admission, and after 3 months, in children with chronic rheumatic heart disease (CRHD) . Plasma NOx concentrations, IL-1alpha and IL/2 levels in patients with ARF on admission were significantly higher than in the same patients 3 months later, and higher than in CRHD, or controls . Increased plasma NO may be a useful index for the quantitative assessment of the activity during immunological challenge . This information may be useful for the prognosis and monitoring of ARF.

Proc Natl Acad Sci U S A, 2003 Apr 29, 100(9), 5087 - 90 Epub 2003 Apr 17.
Group B streptococcal phospholipid causes pulmonary hypertension; Curtis J et al.; Group B Streptococcus is the most common cause of bacterial infection in the newborn . Infection in many cases causes persistent pulmonary hypertension, which impairs gas exchange in the lung . We purified the bacterial components causing pulmonary hypertension and identified them as cardiolipin and phosphatidylglycerol . Synthetic cardiolipin or phosphatidylglycerol also induced pulmonary hypertension in lambs . The recognition that bacterial phospholipids may cause pulmonary hypertension in newborns with Group B streptococcal infection opens new avenues for therapeutic intervention.

Blood, 2003 Aug 1, 102(3), 934 - 9 Epub 2003 Apr 17.
Plasminogen activator inhibitor type-1 deficiency does not influence the outcome of murine pneumococcal pneumonia; Rijneveld AW et al.; Urokinase-type plasminogen activator (uPA) and its receptor uPAR are components of the fibrinolytic system and are important for an adequate immune response to respiratory tract infection, in part through their role in the migration of inflammatory cells . PA inhibitor-1 (PAI-1) is the predominant inhibitor of soluble and receptor-bound uPA . To determine the role of PAI-1 in host defense against pneumococcal pneumonia, the following studies were performed: (1) Patients with unilateral community-acquired pneumonia demonstrated elevated PAI-1 concentrations together with decreased PA activity in bronchoalveolar lavage fluid (BALF) obtained from the infected, but not from the contralateral, site . (2) Mice with Streptococcus pneumoniae pneumonia displayed elevated PAI-1 protein and mRNA levels in their lungs . (3) PAI-1 gene-deficient mice, however, had an unaltered immune response to pneumococcal pneumonia, as measured by cell recruitment into lungs, bacterial outgrowth, and survival . Furthermore, plasminogen-gene-deficient mice also had an unremarkable defense against pneumococcal pneumonia . These data indicate that pneumonia is associated with inhibition of the fibrinolytic system at the site of the infection secondary to increased production of PAI-1; an intact fibrinolytic response is not required for an adequate host response to respiratory tract infection, however, suggesting that the previously described role of uPA and uPAR are restricted to their function in cell migration.

Emerg Infect Dis, 2003 Apr, 9(4), 469 - 73
Invasive group B streptococcal infections in Finland: a population-based study; Lyytikainen O et al.; We analyzed surveillance data on group B streptococcus (GBS) infection in Finland from 1995 to 2000 and reviewed neonatal cases of early-onset GBS infection in selected hospitals in 1999 to 2000 . From 1995 to 2000, 853 cases were reported (annual incidence 2.2-3.0/100,000 population) . We found 32-38 neonatal cases of early-onset GBS disease per year (annual incidence 0.6-0.7/1,000 live births) . In five hospitals, 35% of 26 neonatal cases of early-onset GBS infection had at least one risk factor: prolonged rupture of membranes, preterm delivery, or intrapartum fever . Five of eight mothers screened for GBS were colonized . In one case, disease developed despite intrapartum chemoprophylaxis . Although the incidence of early-onset GBS disease in Finland is relatively low, some geographic variation exists, and current prevention practices are suboptimal . Establishing national guidelines to prevent perinatal GBS is likely to reduce the incidence of the disease.

J Bacteriol, 2003 May, 185(9), 2961 - 6
Essentiality of clpX, but not clpP, clpL, clpC, or clpE, in Streptococcus pneumoniae R6; Robertson GT et al.; We show by using a regulated promoter that clpX of Streptococcus pneumoniae R6 is essential, whereas clpP, clpL, clpC, and clpE can be disrupted . The essentiality of clpX was initially missed because of duplication and rearrangement in the region of the chromosome containing clpX . Depletion of ClpX resulted in a rapid loss of viability without overt changes in cell morphology . Essentiality of clpX, but not clpP, has not been reported previously.

J Biol Chem, 2003 Jul 4, 278(27), 24740 - 52 Epub 2003 Apr 16.
NMR studies of carbohydrates and carbohydrate-mimetic peptides recognized by an anti-group B Streptococcus antibody; Johnson MA et al.; As part of a program to investigate the origins of peptide-carbohydrate mimicry, the conformational preferences of peptides that mimic the group B streptococcal type III capsular polysaccharide have been investigated by NMR spectroscopy . Detailed studies of a dodecapeptide, FDTGAFDPDWPA, a molecular mimic of the polysaccharide antigen, and two new analogs, indicated a propensity for beta-turn formation . Different beta-turn types were found to be present in the trans and cis (Trp-10-Pro-11) isomers of the peptide: the trans isomer favored a type I beta-turn from residues Asp-7-Trp-10, whereas the cis isomer exhibited a type VI beta-turn from residues Asp-9-Ala-12 . The interaction of the dodecapeptide FDTGAFDPDWPA with a protective anti-group B Streptococcus monoclonal antibody has also been investigated, by transferred nuclear Overhauser effect NMR spectroscopy and saturation-transfer difference NMR spectroscopy (STD-NMR) . The peptide was found to adopt a type I beta-turn conformation on binding to the antibody; the peptide residues (Asp-7-Trp-10) forming this turn are recognized by the antibody, as demonstrated by STD-NMR experiments . STD-NMR studies of the interactions of oligosaccharide fragments of the capsular polysaccharide have also been performed and provide evidence for the existence of a conformational epitope.

Front Biosci, 2003 May 01, 8, s533 - 43
Autoimmunity and molecular mimicry in the pathogenesis of post-streptococcal heart disease; Cunningham MW; Molecular mimicry between pathogen and host has been proposed as a mechanism for the development of autoimmune diseases . Evidence suggests that microorganisms contain proteins which are similar enough to host proteins that they can stimulate existing B and T cells to respond to self proteins . The loss of immune regulation during responses against microbial antigens may explain development of pathogenic B and T cell responses in autoimmune diseases associated with infections . The study of B and T cell responses against the group A streptococcal antigens, N-acetyl-glucosamine, M protein and the autoantigen cardiac myosin has led to a better understanding of how molecular mimicry may play a role in disease . Studies of human monoclonal antibodies, T cell responses and animal models in comparison with the immunopathology in the human disease has provided information about the steps leading to inflammatory heart disease in autoimmune post-streptococcal rheumatic carditis . The new data indicate that the steps in pathogenesis of rheumatic heart disease following group A streptococcal infection include the following events . First, the development of crossreactive autoantibodies against the group A streptococcal carbohydrate antigen N-acetyl-glucosamine and cardiac myosin . Second, these antibodies react with valvular endothelium which becomes inflamed with expression of vascular cell adhesion molecule-1 (VCAM-1) . After this event, T cells, CD4+ and CD8+, infiltrate through the endothelium/endocardium into the valve which is an avascular structure . Aschoff bodies or granulomatous lesions may form containing macrophages and T cells underneath the endocardium . The T cells are responsive to streptococcal M protein antigen sequences . The valve becomes scarred with eventual neovascularization and progressive, chronic disease in the valve . In the host, the mimicking antigens cardiac myosin and laminin have been involved in the myocardium and valve, respectively . As in other autoimmune diseases, both environmental and genetic factors are involved in the development of rheumatic carditis and inflammatory heart disease, a result of mimicry between the group A streptococcus and heart.

Infez Med, 2001 Jun, 9(2), 108 - 10
{Preliminary experience with O.P.A.T . (Outpatient parenteral antimicrobial-drug therapy) in infective endocarditis}; Nigro FS et al.; The authors evaluated the efficacy and safety of an OPAT program in a small group of patients affected by infective endocarditis . Three patients were considered eligible for the treatment; i.e . they had a stable hemodynamic balance and no embolic events . Streptococcus spp . grew in blood cultures of two patients, while blood cultures were negative in the third patient . Long-acting antibiotics were used and all patients recovered from the infection without adverse events . The treatment was efficacious and safe . This preliminary experience suggests that OPAT programs can be promoted in infective endocarditis with advantage . Strictness and caution are necessary in screening and monitoring patients.

Infez Med, 2001 Jun, 9(2), 101 - 7
{Cellulitis and soft tissue infection in patients with HIV disease: epidemiological and microbiological features}; Manfredi R et al.; In order to assess the epidemiological, microbiological, and clinical features of cellulitis and soft tissue infection occurring during the course of HIV disease, clinical and laboratory data of 2221 hospitalizations carried out since 1991 were retrospectively examined, and 67 bacteriologically-proven episodes of cellulitis-soft tissue infection were identified (3.02% of overall admissions) . Among the 92 cultured pathogens, Staphylococcus aureus was the most frequent (46 cases), followed by Pseudomonas spp., Escherichia coli, and Streptococcus pyogenes; 38.1% of patients had a polymicrobial infection . i.v . drug use (p<.02) and the male gender (p<.05), were significantly associated with the occurrence of these complications, while a great variation in the severity of underlying immunodeficiency was shown . An elevated rate (83.6%) of episodes of cellulitis or soft tissue infection were community-acquired in origin; the comprehensive frequency of these episodes significantly dropped during the highly active antiretroviral therapy (HAART) era (p<.01) . Limbs were involved in over 80% of episodes, and an hematogenous dissemination of bacterial infection (which occurred in 25.4% of cases), proved significantly related to a CD4+ lymphocyte count <100 cells/microL (p<.03), and an absolute neutrophil count <1000 cells/microL (p<.05) . S . aureus strains showed an elevated in vitro resistance rate to penicillin, ampicillin, and rifampin, and a 21.7% rate of methicillin-resistance, while among the 29 gram-negative microorganisms, resistance to ampicillin and first-generation cephalosporins, and that to amoxycillin-clavulanate and second-generation cephalosporin, occurred in over 90% and 60% of tested strains, respectively . All episodes of HIV-associated cellulitis and soft tissue infection were favorably treated in 5-16 days, in over 60% of cases with associated beta-lactam and aminoglycoside antibiotics; a recurrence of staphylococcal cellulitis occurred in 4 patients only, 6-17 months after the initial episode . Cellulitis and soft tissue infection are underestimated complications of HIV disease, but they have a broad etiological and clinical spectrum, are predominantly community-acquired, and are responsible for an appreciable morbidity, due to the supporting role of i.v . drug addiction, and the frequent hematogenous dissemination (which proved to be significantly related to the progression of immunodeficiency and underlying disease) . The frequent polymicrobial etiology requires a combination antimicrobial therapy (to be guided by in vitro susceptibility studies), which may avoid a complicated and recurrent disease course in the great majority of cases.

Biomedica, 2003 Mar, 23(1), 77 - 86
{Molecular characterization of invasive isolations of penicillin-resistant Streptococcus pneumoniae recovered from adult patients}; Moreno J et al.; Streptococcus pneumoniae penicillin resistance is associated with the international dispersion of specifically identified strains . In Colombia, the presence and circulation of resistant strains Spain23F-1, Spain6B-2, Spain9V and Colombian23F-25 has been demonstrated in children less than 5 years old . Strain identities were established for 80 penicillin resistant S . pneumoniae isolates recovered from Colombian adult patients . Three approaches to genotypic characterization of the strains wrere used: a) chromosomal DNA was digested with Sma 1, and the products subjected to pulse-field gel electrophoresis (PFGE); b) restriction enzyme fragment comparison of the penicillin binding protein genes (pbp 1a, 2b and 2x), and c) pneumococcal surface protein A (PspA) family . The results showed that 2.5% of the isolates were genetically related to Spain23F-1 clone, 10% to Spain6B-2 clone, 37.5% to Spain9V-3, in addition, 14% of the capsular type 23F isolates were related to the Colombia23F-25 clone and demonstrated an intermediate level resistance to penicillin . Wide spread circulation of international strains as well as a Colombian strain highlighted the importance of these clones in maintaining the prevalence of resistance to penicillin in Colombia.

FEMS Microbiol Lett, 2003 Apr 11, 221(1), 73 - 9
Functional analysis of a PcsB-deficient mutant of group B streptococcus; Reinscheid DJ et al.; Group B streptococcus (GBS) is the major cause of bacterial sepsis and meningitis in neonates and poses a significant threat to parturient women . Recently, we identified in GBS the polypeptide PcsB, which is a protein required for cell separation of GBS, and which is also involved in the antibiotic sensitivity of these bacteria . In the present study, the introduction of the pcsB-carrying plasmid pATpcsB into the PcsB-deficient GBS mutant Sep1 restored the phenotype and the antibiotic susceptibility of this strain to that of the GBS wild-type . Although Northern blots revealed a four- to five-fold increased transcription of pcsB in pATpcsB-carrying GBS strains, overexpression of pcsB did not result in higher amounts of PcsB in the cell wall and in the culture supernatant of GBS, indicating regulatory mechanisms that control the translation or secretion of PcsB in these bacteria . In the culture supernatant of mutant Sep1 significant amounts of enolase were identified . As this protein was also present in extracts of cell wall-bound proteins from the GBS wild-type, it can be speculated that GBS can translocate enolase across the cytoplasmic membrane . Northern blot analysis exhibited similar expression of the enolase gene in the GBS strains 6313 and Sep1, indicating that mutant Sep1 is impaired in the anchoring of this protein to its cell wall.

J Calif Dent Assoc, 2003 Mar, 31(3), 211 - 4
A review of the efficacy of chlorhexidine on dental caries and the caries infection; Anderson MH; Chlorhexidine has been used for the past 35 years in the treatment of the two primary diseases of dentistry with varying degrees of success . The purpose of this paper is to review the literature for both the caries reduction potential and the microbiologic reduction of the pathogens associated with dental caries . The literature remains mixed on the success of chlorhexidine for the reduction of dental caries . Its performance as an antimicrobial against Streptococcus mutans is more consistent and favorable.

J Calif Dent Assoc, 2003 Mar, 31(3), 205 - 9
Xylitol and dental caries: an overview for clinicians; Lynch H et al.; An overview of studies about xylitol and dental caries suggests potential clinical dental applications for xylitol . Xylitol is a naturally occurring, low-calorie sugar substitute with anticariogenic properties . Data from recent studies indicate that xylitol can reduce the occurrence of dental caries in young children, schoolchildren, and mothers, and in children via their mothers . Xylitol, a sugar alcohol, is derived mainly from birch and other hardwood trees . Short-term consumption of xylitol is associated with decreased Streptococcus mutans levels in saliva and plaque . Aside from decreasing dental caries, xylitol may also decrease the transmission of S . mutans from mothers to children . Commercial xylitol-containing products may be used to help control rampant decay in primary dentition . Studies of schoolchildren in Belize and Estonia, along with data from the University of Washington, indicate that xylitol gum, candy, ice pops, cookies, puddings, etc., in combination with other dental therapies, are associated with the arrest of carious lesions . A prospective trial in Finland has demonstrated that children of mothers treated with xylitol had lower levels of S . mutans than children of mothers treated with chlorhexidine or fluoride varnish . Food products containing xylitol are available commercially and through specialized manufacturers, and have the potential to be widely accessible to consumers.

Am J Rhinol, 2003 Jan-Feb, 17(1), 9 - 15
Microbiology of middle meatus in chronic rhinosinusitis; Araujo E et al.; BACKGROUND: Nasal endoscopy allows the collection of middle meatus secretion samples and is an alternative method for determining microorganisms in rhinosinusitis . This study assessed endoscopically collected middle meatus secretions in patients with chronic rhinosinusitis (CRS) and compared those findings with ipsilateral maxillary sinus aspirates and microbiological data of healthy individuals . METHODS: Middle meatus samples were collected from 114 CRS patients for aerobic, anaerobic, and fungal cultures; maxillary sinus secretions were collected from 13 of these patients . Twenty-three healthy volunteers served as controls . RESULTS: Aerobes were isolated in 86% of CRS patients, anaerobes were isolated in 8% of CRS patients, and fungi were isolated in 11% of CRS patients; the most frequent microorganisms were Staphylococcus aureus (36%), coagulase-negative Staphylococcus (20%), and Streptococcus pneumoniae (17%) . Middle meatus and maxillary sinus cultures presented the same pathogens in 80% of cases . In healthy individuals, coagulase-negative Staphylococcus (56%), S . aureus (39%), and S . pneumoniae (9%) were the most frequent isolates . CONCLUSION: The culture of endoscopically collected middle meatus secretions is effective in identifying microorganisms in CRS patients.

Scand J Infect Dis, 2003, 35(2), 141 - 3
Postoperative pneumococcal cellulitis in systemic lupus erythematosus; Page KR et al.; This paper reports a case of nosocomial pneumococcal cellulitis that developed following a lymph-node biopsy in a woman being treated with high-dose intravenous corticosteroids for systemic lupus erythematosis (SLE) . Her rapid and severe clinical deterioration was similar to that caused by group A streptococcus . The risk factors for the development of nosocomial pneumococcal cellulitis as a complication of SLE are reviewed and preventive measures discussed.

S D J Med, 2003 Mar, 56(3), 103 - 7
Middle ear pathogens in otitis-prone children; Weiner R et al.; A cohort of 191 children with recurrent otitis media and persistent middle ear effusion underwent myringotomy and tubes, at which time middle ear cultures were taken . The indications, fluid type, culture and sensitivity results, and pre- and post-procedure frequency of otitis media were evaluated . Sixty-seven percent of the effusions were mucoid in nature, and 24% of cultures grew pathogens, including Hemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus in that order of frequency . A relatively high rate of antibiotic resistance was noted, with 75% of Streptococcus pneumoniae being penicillin resistant . Prognosis with respect to recurrent otitis media was favorable after myringotomy and tubes, even in children with antibiotic-resistant organisms.

Clin Microbiol Rev, 2003 Apr, 16(2), 308 - 18
Pneumococcal vaccination and revaccination of older adults; Artz AS et al.; As individuals advance in age, the risk of infection, bacteremia, and mortality caused by Streptococcus pneumoniae rises . Retrospective data demonstrate that the licensed penumococcal polysaccharide vaccine (PPV) is effective in older persons in reducing serotype-specific invasive disease . PPV demonstrates good immunogenicity in older adults, generally comparable to that in younger subjects, although certain cohorts respond less well . The response to PPV is T cell independent, however, and does not elicit immunologic memory . The duration of the anti-capsular polysaccharide antibody response appears to wane as early as 3 years after vaccination . In older persons, revaccination induces an antibody response, although it may not be as strong as that from the initial vaccine . While revaccination of older adults has been recommended, clinical efficacy has not yet been proven . Measures of antibody function may be at least as important in determining protection as are quantitative antibody levels . Additional studies of immunogenicity, particularly regarding revaccination, will facilitate the design of an optimal pneumococcal vaccination policy . Research into conjugate- and protein-based pneumococcal vaccines, which elicit T-cell-dependent responses and induce immunologic memory, is needed in older persons . In the meantime, administering to PPV to recommended groups should be a public health priority.

Dis Aquat Organ, 2003 Feb 27, 53(3), 241 - 7
Streptococcus iniae: serological differences, presence of capsule and resistance to immune serum killing; Barnes AC et al.; The biochemical profiles, presence of capsule, outer membrane protein profiles and serological interactions of isolates of Streptococcus iniae obtained from different geographical and fish host origins were examined . The isolates had very similar biochemical profiles using API 20 Strep but varied as to whether they were arginine dihydrolase-negative, -positive or -intermediate (AD-ve, AD+ve, AD+/-ve, respectively) . Representatives of each AD type were compared in subsequent experiments . All types possessed a polysaccharide capsule . Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of outer membrane proteins or whole cells revealed no difference in banding patterns between isolates . All isolates were resistant to trout normal and specific immune serum and grew well in the presence of added fresh normal serum . Serological analyses of the isolates revealed antigenic differences . Trout antiserum against the AD+ve isolate did not agglutinate the AD-ve or AD+/-ve isolates, while antisera against the latter 2 types showed low agglutinating activity with all 3 isolates . When whole live cells of AD-ve and AD+ve isolates were dot-blotted, antiserum to the AD+ve isolate did not stain the AD-ve isolate, but antiserum to the AD-ve isolate stained both AD types . However, if the cells were pre-treated with Proteinase K (to remove surface-exposed protein antigens), the AD+ve isolate was stained only by its homologous antiserum . These results suggest that while certain protein antigens of the different AD type strains are immunologically cross-reactive, the capsular antigens appear to be AD type-specific . Furthermore, the results suggest that the cross-reactive antigens on the AD-ve isolate are effectively hidden by the strain-specific capsule, while they are partially exposed on the AD+ve isolate.

Pediatr Infect Dis J, 2003 Apr, 22(4), 315 - 23
Linezolid versus cefadroxil in the treatment of skin and skin structure infections in children; Wible K et al.; BACKGROUND: Skin and skin structure infections are common reasons for visits to pediatricians, accounting for up to 18% . Staphylococcus aureus and Streptococcus pyogenes are the most frequently isolated Gram-positive pathogens in uncomplicated skin infections . Increasingly outpatient infections involve antibiotic-resistant Gram-positive pathogens including methicillin-resistant S . aureus . METHODS: This randomized, blinded, comparator-controlled, multinational trial compared the efficacy and safety of linezolid and cefadroxil for treatment of uncomplicated skin/skin structure infections in pediatric patients . Children ages 5 to 11 years were to receive linezolid suspension {10 mg/kg (up to 600 mg)} or cefadroxil suspension {15 mg/kg (up to 500 mg)} every 12 h . Patients ages 12 to 17 years were to receive linezolid tablets (600 mg) or cefadroxil capsules (500 mg) every 12 h . Therapy lasted 10 to 21 consecutive days with a follow-up visit 10 to 21 days posttherapy . RESULTS: Linezolid and cefadroxil were consistently effective treatments across all primary and secondary efficacy assessments . At follow-up cure rates were 88.7% (205 of 231) for linezolid-treated and 86.2% (193 of 224) for cefadroxil-treated intent-to-treat patients; cure rates were 91.0% (201 of 221) for linezolid-treated and 90.0% (189 of 210) for cefadroxil-treated clinically evaluable patients . S . aureus was eradicated in 89.6% (120 of 134) linezolid-treated and 88.8% (111 of 125) cefadroxil-treated microbiologically evaluable patients . Gastrointestinal complaints were the most common adverse events reported, without significant differences between treatment groups, and myelosuppression was not observed in this study . CONCLUSIONS: Linezolid is well-tolerated and as effective as cefadroxil in treating uncomplicated skin infections in pediatric patients . Linezolid effectively treated infections caused by S . aureus, methicillin-resistant S . aureus and S . pyogenes.

Ophthalmology, 2003 Apr, 110(4), 743 - 7
Infectious keratitis after photorefractive keratectomy; Donnenfeld ED et al.; PURPOSE: To elucidate risk factors, microbial culture results, and visual outcomes for infectious keratitis after photorefractive keratectomy (PRK) . DESIGN: Multicenter, retrospective chart review, case report, and literature review . METHODS: The records of 12 patients with infectious keratitis after PRK were reviewed . MAIN OUTCOME MEASURES: Causative organism, response to medical treatment, and visual outcome . RESULTS: Infectious keratitis developed in 13 eyes of 12 patients after PRK . Organisms cultured were Staphylococcus aureus (n = 5), including a bilateral case of methicillin-resistant Staphylococcus aureus; Staphylococcus epidermidis (n = 4); Streptococcus pneumoniae (n = 3); and Streptococcus viridans (n = 1) . Four patients manipulated their contact lenses, and 2 patients were exposed to nosocomial organisms while working in a hospital environment . Prophylactic antibiotics used were tobramycin (nine cases), polymyxin B-trimethoprim (three cases), and ciprofloxacin (one case) . Final best spectacle-corrected visual acuity ranged from 20/20 to 20/100 . CONCLUSIONS: Infectious corneal ulceration is a serious potential complication of PRK . Gram-positive organisms are the most common pathogens . Antibiotic prophylaxis should be broad spectrum and should include gram-positive coverage.

J Coll Physicians Surg Pak, 2003 Mar, 13(3), 146 - 9
Increased risk of cervical canal infections with intracervical Foley catheter; Siddiqui S et al.; OBJECTIVE: To evaluate the effect of intracervical Foley catheter insertion, for the induction of labor, on cervical canal infection . DESIGN: A prospective interventional study with paired analysis . PLACE AND DURATION OF STUDY: The study was conducted in the department of Obstetrics and Gynecology at the Aga Khan University, Karachi, between June 1 and August 31, 2002 . SUBJECTS AND METHODS In 45 women undergoing cervical ripening with intracervical Foley catheter for the induction of labour at term, cervical swabs were taken for culture and sensitivity before its insertion and again after its spontaneous expulsion or removal . RESULTS: Intracervical Foley catheter was retained for mean duration of 8.1 +/- 1.7 hours . There was a significant change in the pathogenic organisms (0 % v 16.3 %; p 0.016) from pre-Foley to post-Foley catheter cervical swab cultures . Growth of beta-hemolytic Streptococcus group-B, Candida albicans, Candida glabrata and Gardnerella vaginalis on cervical swab were considered pathogenic . One woman (2.2 %) developed fever following insertion of intracervical Foley catheter . No statistically significant effect of potential confounding factors was observed on change in growth of pathogenic organisms . CONCLUSION: Induction of labour at term with Foley catheter is associated with a significant increase in intracervical pathogenic organisms despite undertaking routine aseptic measures . We recommend evaluation of this technique for its potential infectious harm in larger studies . Meanwhile, extreme aseptic measures should be undertaken during its insertion to avoid maternal and possible neonatal infections.

J Clin Microbiol, 2003 Apr, 41(4), 1794 - 7
drs (Distantly related sic) gene polymorphisms among emm12-type Streptococcus pyogenes isolates; Brandt CM et al.; Twenty-eight emm12-type Streptococcus pyogenes isolates from patients with invasive and noninvasive infections or from asymptomatic carriers were genetically typed . Sequencing of drs (distantly related sic {streptococcal inhibitor of complement}) genes identified two novel alleles and revealed a polymorphism for drs similar to that of sic . No association was observed between the five different drs alleles and the five restriction patterns of the vir regulon for the isolates studied . These data suggest that drs sequencing may be useful for further differentiation of S . pyogenes isolates with emm12 and identical vir regulon restriction patterns.

J Exp Med, 2003 Apr 7, 197(7), 939 - 45
Human immunoglobulin M memory B cells controlling Streptococcus pneumoniae infections are generated in the spleen; Kruetzmann S et al.; Splenectomized and asplenic patients have a high incidence of infections by encapsulated bacteria and do not respond to polysaccharide vaccines . To understand whether the absence of the spleen is associated with a defined B cell defect, we analyzed B cell subsets in the peripheral blood . We found that a population of B cells known as immunoglobulin (Ig)M memory is lacking in patients without spleen . The absence of IgM memory B cells correlates with an impaired immune response to encapsulated bacteria not only in splenectomized patients, but also in individuals with an intact spleen . We show that the physiological and transient predisposition to pneumococcal infections of young children (0-2 yr) is associated with the lack of circulating IgM memory B cells and of serum antipolysaccharide IgM . We also demonstrate that IgM memory B cells are undetectable in a fraction of patients with common variable immunodeficiency, who have recurrent and invasive infections by encapsulated bacteria . IgM memory B cells, therefore, require the spleen for their generation and/or survival and are responsible for the protection against encapsulated bacteria.

Enferm Infecc Microbiol Clin, 2003 Apr, 21(4), 174 - 9
{Decreasing incidence of perinatal group B streptococcal disease (Barcelona 1994-2002) . Relation with hospital prevention policies}; Andreu A et al.; INTRODUCTION: To analyze the incidence of perinatal sepsis due to group B streptococcus (GBS) as related to compliance with recommendations for its prevention issued by the Catalan Societies for Obstetrics, for Pediatrics, and for Infectious Diseases and Clinical Microbiology in 1997 . METHODS: The study was conducted from 1994 to 2001 in 10 Barcelona-area hospitals, where 157,848 live infants were born . RESULTS: GBS disease was diagnosed in 129 neonates . Incidence decreased by 86.1% over the study period, from 1.92 cases per 1000 live births in 1994 to 0.26 per 1000 in 2001 (p < 0.001) . Changes in the characteristics of perinatal GBS disease were observed in the 18 cases diagnosed in the last 3 years, the time when prevention policies were operative . The incidence was lower (0.28 per 1000 vs . 1.19 for the previous 5 years, p <.00006), the proportion of mothers without risk factors was greater (77.8% vs . 55.9%, p 5 0.009), and premature neonates were not affected (0% vs . 12.6%, p 5 0.003); nevertheless, mortality was similar (5.5% vs . 4.5%, p 5 0.8) . Among these 18 cases of sepsis, 9 can be considered failures inherent to the prevention policy and 9 failures of compliance . Only 3 hospitals had prevention policies in 1994, whereas all 10 used intrapartum prophylaxis based on screening results in 2001 . CONCLUSIONS: A substantial decrease in the incidence of perinatal GBS disease coinciding with the application of prevention measures for this pathology has been registered in 10 participating hospitals over the 1994-2001 period.

Russ J Immunol, 1998 Apr, 3(1), 29 - 36
Some Peculiarities of Humoral Antibacterial Immunity in HIV-infected and AIDS Patients; Kulakov AV et al.; The investigation was outlined to study antibodies against some antigens of extracellular microbes associated with inflammation in broncho-pulmonary system and accessory nasal sinus - Staphylococcus aureus, Streptococcus pneumoniae, Branhamella catarrhalis - in individuals (18 patients) with different stages of HIV-infection . The level of antibodies was measured by ELISA and their Ab affinity was assessed by sodium thiocyanate-induced alteration of antibody-antigen interaction . To determine interrelations between antibody production and CD4(+) T lymphocyte number flow cytometry was employed . At the early stages of HIV-infection the levels of antibodies against Streptococcus pneumoniae and GMGM decreased, in comparison with HIV-negative donors . During HIV-infection course levels of antibodies against Staphylococcus aureus peptidoglycan, its antigen determinants and Streptococcus pneumoniae somatic antigen increased . Time affinity of antibodies against these antigens decreased . At all stages of HIV-infection and at all forms of its complications, we observed an increase of titer of antibodies to GMDP, antigenic determinant of peptidoglycan, which carried immunostimulating and adjuvant activities . HIV patients with CD4(+) T lymphocyte number <200 cells/&mgr;l displayed higher level of antibodies to bacterial antigens than that in patients with CD4(+) T lymphocyte number 200-400 per ml . The development of humoral immune response against some of extracellular bacteria is characterized, on the one hand, by their increased levels, and on the other hand, decreased affinity.

Dent Mater, 2003 Jun, 19(4), 313 - 9
Antibacterial activity and bonding characteristics of an adhesive resin containing antibacterial monomer MDPB; Imazato S et al.; OBJECTIVES: The aims of this study were to investigate the antibacterial activity of an adhesive resin incorporating the antibacterial monomer 12-methacryloyloxydodecylpyridinium bromide (MDPB) as well as its bonding characteristics in terms of bond strength into dentin and curing ability . METHODS: An experimental adhesive resin was prepared by incorporation of 2.5% MDPB into proprietary adhesive (LB Bond), and the inhibitory effect of cured specimen against the growth of Streptococcus mutans on its surface was determined . Bond strength to human dentin and degree of conversion of the experimental adhesive in combination with 1, 2, or 5% MDPB-containing primers, which were previously reported to possess bactericidal effect, were evaluated by conventional tensile bond strength test and Fourier transformation infrared spectroscopy . RESULTS: The cured experimental adhesive exhibited an inhibitory effect on S . mutans growth, reducing the number of bacteria to approximately 3% of control adhesive without MDPB . Tensile bond strength of experimental adhesive was not significantly different from that of the control (p>0.05), and use in combination with MDPB-containing primer did not show any adverse influence on bond strength . The degree of conversion of the bonding system was not different (p>0.05) between control and experimental adhesive irrespective of addition of MDPB into primer . SIGNIFICANCE: These results indicate that an adhesive resin with antibacterial activity after curing could be produced by incorporation of MDPB without influencing bond strength or curing performance, suggesting that the comprehensive bonding system including MDPB-containing primer and adhesive should be highly effective in its antibacterial effect before and after curing.

Clin Infect Dis, 2003 Apr 15, 36(8), 963 - 70 Epub 2003 Apr 02.
Factors associated with relative rates of antimicrobial resistance among Streptococcus pneumoniae in the United States: results from the TRUST Surveillance Program (1998-2002); Karlowsky JA et al.; To identify factors associated with antimicrobial resistance, data were analyzed from 27,828 isolates of Streptococcus pneumoniae submitted to the Tracking Resistance in the United States Today (TRUST) surveillance program during 4 consecutive respiratory seasons . From the 1998-1999 season to the 2001-2002 season, the prevalence of azithromycin resistance increased by 4.8% to 27.5%, the prevalence of penicillin resistance increased by 3.7% to 18.4%, the prevalence of ceftriaxone resistance increased by 0.5% to 1.7%, and the prevalence of levofloxacin resistance increased by 0.3% to 0.9% . Isolates recovered from patients <18 years of age and lower respiratory tract specimens had elevated rates of penicillin, azithromycin, and trimethoprim-sulfamethoxazole resistance (P<.00001); penicillin resistance correlated with coresistance to trimethoprim-sulfamethoxazole (87.3%), azithromycin (76.3%), ceftriaxone (9.1%), and levofloxacin (1.3%) (P<.00001) . Only 62 (0.2%) of 27,828 isolates were concurrently resistant to penicillin and levofloxacin . Minimum inhibitory concentrations (MICs) of penicillin correlated strongly with MICs of ceftriaxone (R2=0.90), trimethoprim-sulfamethoxazole (R2=0.53), and azithromycin (R2=0.41) . Patient age, specimen source, and penicillin resistance were factors associated with antimicrobial resistance, particularly for nonfluoroquinolone antimicrobial agents.

Med Microbiol Immunol (Berl), 2003 Aug, 192(3), 149 - 55 Epub 2003 Mar 05.
Pathogenesis of Adamantiades-Behçet's disease; Zouboulis CC et al.; The aetiology of Adamantiades-Behcet's disease remains unknown and its pathogenesis is not fully understood . Linked intrinsic and extrinsic factors are thought to contribute to the development of the disease, which probably occurs by environmental triggering of a genetically determined disorder . Transmission is solely vertical, indicating that the disease is not contagious . Genetic factors have been investigated and a significant link of HLA-B51, especially of HLA-B5101, has been identified . However, none of the functional correlates of the disease appear to be restricted by HLA-B51 . Recently, the role of the genes encoding TNF, Tap proteins and MICA has been emphasised . Extrinsic pathogenetic candidates have been identified, including bacterial ( Streptococcus sanguis, Mycoplasma fermentas) and viral (human herpes virus) antigens and environmental pollution, which may cross-react with oral mucosal antigens and induce immunological mechanisms . A common factor linking some of the possible pathogenetic agents is extrinsically induced tissue stress or heat shock proteins, which react with host tissues and elicit significant Th1 cell responses . Neutrophils may also play a role in the pathogenesis of the disease, as they are attracted by macrophages and activated endothelial cells, which release cytokines and chemokines (especially IL-8) at the site of the lesions, and thus contribute to tissue damage and self maintenance of inflammation . Endothelial activation leading to a chronic local inflammation process together with platelet and serum factors enhance coagulation and thrombosis.

Lancet Infect Dis, 2003 Apr, 3(4), 191 - 200
Molecular basis of group A streptococcal virulence; Bisno AL et al.; The group A streptococcus (GAS) (Streptococcus pyogenes) is among the most common and versatile of human pathogens . It is responsible for a wide spectrum of human diseases, ranging from trivial to lethal . The advent of modern techniques of molecular biology has taught much about the organism's virulence, and the genomes of several GAS types have now been deciphered . Surface structures of GAS including a family of M proteins, the hyaluronic acid capsule, and fibronectin-binding proteins, allow the organism to adhere to, colonise, and invade human skin and mucus membranes under varying environmental conditions . M protein binds to complement control factors and other host proteins to prevent activation of the alternate complement pathway and thus evade phagocytosis and killing by polymorphonuclear leucocytes . Extracellular toxins, including superantigenic streptococcal pyrogenic exotoxins, contribute to tissue invasion and initiate the cytokine storm felt responsible for illnesses such as necrotising fasciitis and the highly lethal streptococcal toxic shock syndrome . Progress has been made in understanding the molecular epidemiology of acute rheumatic fever but less is understood about its basic pathogenesis . The improved understanding of GAS genetic regulation, structure, and function has opened exciting possibilities for developing safe and effective GAS vaccines . Studies directed towards achieving this long-sought goal are being aggressively pursued.

J Bone Joint Surg Br, 2003 Mar, 85(2), 277 - 8
Malignant necrotising streptococcal myositis: a rare and fatal condition; Subramanian KN et al.; We present a case of fatal 'malignant' necrotising streptococcal myositis in a previously healthy 39-year-old man . The infection was caused by Lancefield group-A haemolytic streptococcus highlights the clinical features and the necessity of prompt aggressive treatment.

Can Vet J, 2003 Mar, 44(3), 217 - 20
Serotypes of Streptococcus agalactiae cultured from dairy milk samples in Québec; Daignault D et al.; Streptococcus agalactiae remains an important pathogen of dairy herds in Quebec, but data about antigenic characteristics of this microorganism are sparse . This study was conducted to determine the variety of S . agalactiae serotypes in dairy herds in Quebec . Two hundred and ninety-five isolates cultured from the milk of individual cows from 7 regions of Quebec were serotyped . Sixty-two percent of the isolates were untypable . Among the 38% of typeable isolates, serotype III was found most frequently . In conclusion, the heterogeneity found among antigenic determinants of isolates from bovine milk suggests that an immunological method for the detection of S . agalactiae performed directly on bovine milk would not be a practical approach.

Skin Pharmacol Appl Skin Physiol, 2003 May-Jun, 16(3), 176 - 87
Palmitoleic acid isomer (C16:1delta6) in human skin sebum is effective against gram-positive bacteria; Wille JJ et al.; The percent lipid composition of pooled human sebum analyzed by thin-layer chromatography was: ceramides (13%), fatty acid (47%), cholesterol (7%), cholesterol esters (2%), squalene (11%), triglycerides (3%), and wax esters (17%) . Total sebum lipids (2- 4 mg/ml), sonicated into bacterial culture medium, caused 4- to 5-fold log reduction in growth of gram-positive bacteria, Staphylococcus aureus, Streptococcus salivarius and the anaerobe Fusobacterium nucleatum, but was ineffective against most gram-negative bacteria . Fractionation of the sebum lipids showed that both saturated and unsaturated fatty acids contained the bulk of the antimicrobial activity . Lauric acid (C12:0) was the most active saturated fatty acid . The unsaturated fatty acid, palmitoleic acid (C16:1delta6, cPA) was both the most predominant monoene and the most active antimicrobial fatty acid . Purified cPA (>99%) yielded typical minimal inhibitory concentration (MIC) values of 10-20 microg/ml against gram-positive bacteria . Organically synthesized cPA isomer gave MIC values comparable to the natural material . Both natural and synthetic cPA were found to be the most active sebum lipid fraction in blocking the adherence of a pathogenic strain of Candida albicans to porcine stratum corneum . Ethanol in combination with cPA exerts a synergistic bactericidal activity against gram-negative pathogenic bacteria, including Pseudomonas aeruginosa, Propionibacterium acnes, Escherichia coli, and several methacillin-resistant strains of S . aureus . Palmitoleic acid may be useful in topical formulations for treatment of secondary gram-positive bacterial infections, as a gram-positive bacteria antimicrobial in wound dressings, and as a natural gram-positive antimicrobial preservative in skin and hair care products .

J Med Microbiol, 2003 Apr, 52(Pt 4), 337 - 44
Towards a genotyping system for Streptococcus agalactiae (group B streptococcus): use of mobile genetic elements in Australasian invasive isolates; Kong F et al.; This study forms part of the development of an integrated genotyping system for Streptococcus agalactiae (group B streptococcus, GBS) that can be used to study the population genetics of the organism and the pathogenesis and epidemiology of GBS disease . In recent previous studies, two sets of markers, the capsular polysaccharide synthesis (cps) gene cluster and surface protein antigen genes, have been used to assign molecular serotypes (MS) and protein-gene profiles (PGP) to more than 200 isolates . In the present study, five mobile genetic elements (MGE) have been used as a third set of markers, to characterize further 194 invasive isolates, recovered from blood or cerebrospinal fluid (CSF) . Of these, 97 % contained one or more of the five MGE, the distribution of which was related to MS and PGP, as illustrated by MS III, which is divisible into four serosubtypes with different combinations of the MGE (or none) . Fifty-six different genotypes and eight genetic clusters were identified, each with different combinations of the three sets of molecular markers . Five predominant genotypes (Ia-1, Ib-1, III-1, III-2 and V-1) contained 62 % of the isolates and five of the eight genetic clusters contained 92 % of the isolates . The 17 CSF isolates were relatively widely distributed between 10 genotypes and across seven of the eight clusters . Further study is needed to determine whether these genotypes or clusters share common markers of increased virulence . In future, comparison of invasive with colonizing strains of GBS may elucidate the significance of these findings.

Cell Microbiol, 2003 Apr, 5(4), 253 - 65
Streptococcus pyogenes expressing M and M-like surface proteins are phagocytosed but survive inside human neutrophils; Staali L et al.; Strains of the Gram-positive human pathogen Streptococcus pyogenes (group A streptococcus) that express surface-associated M or M-like proteins survive and grow in non-immune fresh human blood . This is generally accepted to be caused by an antiphagocytic property of these proteins . However, in most previous studies, an inhibition of the internalization of the bacteria into host cells has not been studied or not directly demonstrated . Therefore, in the present paper, we used flow cytometry, fluorescence microscopy and electron microscopy to study phagocytosis by human neutrophils of wild-type S . pyogenes and strains deficient in expression of M protein and/or the M-like protein H . The results demonstrate that all strains of S . pyogenes tested, including the wild-type AP1 strain, induce actin polymerization and are efficiently phagocytosed by human neutrophils . In addition, using classical bactericidal assays, we show that the wild-type AP1 strain can survive inside neutrophils, whereas mutant strains are rapidly killed . We conclude that the ability of virulent S . pyogenes to survive and multiply in whole blood is most likely not possible to explain only by an antiphagocytic effect of bacterial surface components . Instead, our data suggest that bacterial evasion of host defences occurs intracellularly and that survival inside human neutrophils may contribute to the pathogenesis of S . pyogenes and the recurrence of S . pyogenes infections.

Medicina (B Aires), 2003, 63(1), 9 - 14
Adult bacteremic pneumococcal pneumonia acquired in the community . A prospective study on 101 patients; Gentile JH et al.; Our objective was to describe incidence, clinical, radiographic and microbiological features of bacteremic pneumococcal pneumonia (BPP) in our environment . A total of 101 patients (7 were treated as outpatients), older than 18 years of age suffering BPP were prospectively evaluated . The incidence was 2.8 cases per 1000 admissions, 50 were males, mean age was 59.9 years (19-97), mortality was 11.8% . Eighty three percent of fatalities occurred within 3 days of admission . Mortality rate increased with advancing age . Fever, cough and chest pain were the commonest presenting symptoms and 44% of patients had extrapulmonary manifestations . Cigarette smoking, chronic obstructive lung disease, alcoholism and congestive heart failure (CHF) were the commonest underlying conditions . CHF was more frequent in non-survivors (p = 0.002) . A lobar pattern at chest radiograph predominated in survivors and a diffuse pattern in non-survivors (p = 0.007) . Pleural effusion (20.7%), empyema (7.9%) and respiratory failure (7.9%) were the main complications . Underlying diseases were present in 100% of non-survivors (p = 0.03) . Ninety four percent of patients were treated with beta-lactam antibiotics . Streptococcus pneumoniae was isolated from sputum in 6 cases . Three out of 101 S . pneumoniae isolates recovered from blood samples (one from each patient) presented organisms resistant to penicillin . We observed an incidence of BPP that is similar to the observed in other countries . There are clinical and radiographic differences between survivors and non-survivors . Penicillin-resistant S . pneumoniae is still an unusual problem in our area.

Medicina (B Aires), 2003, 63(1), 1 - 8
{Community-acquired pneumonia in patients in 2 hospital populations}; Caberlotto OJ et al.; Patients hospitalized with community acquired pneumonia were studied prospectively in two hospitals located in the surroundings of Buenos Aires city . Fifty two patients from General Hospital Manuel Belgrano (HMB) were included from March 1998 to February 1999 and 23 patients from Hospital Dr A . Cetrangolo (HCET) for respiratory disease, were included from June 2000 to May 2001 . Patients with lung tuberculosis, lung neoplasia and HIV infection were excluded . Clinical background, signs and symptoms were recorded . Microbiological examinations performed included bacteria, respiratory viruses and mycobacteria . Studies for "atypical" bacteria (Chlamydia spp., Coxiella burnetii, Mycoplasma pneumoniae and Legionella spp.) were carried out by serological methods . No differences in age and gender were observed between both groups . Most frequently observed comorbidities in the HMB group included COPD, diabetes and cardiac failure while in the HCET group these were COPD, asthma and lung fibrosis . Etiology was established in 48% and 65.2% of the patients in the first and second group, respectively . Most frequent agents were Mycoplasma pneumoniae, Streptococcus pneumoniae, influenza A and Legionella spp.; the last one was detected in 12% of the patients . Most of these patients were from HMB and presented a good outcome . Mortality was similar in both groups (13.3%) . In the HBM group it was related to the presence of comorbidities in 7 out of 8 cases, and in the HCET group it was a consequence of the worsening of their chronic respiratory failure.

Am J Physiol Cell Physiol, 2003 Aug, 285(2), C253 - 9 Epub 2003 Apr 02.
A novel method to quantify the turnover and release of monocytes from the bone marrow using the thymidine analog 5'-bromo-2'-deoxyuridine; Goto Y et al.; The present study was designed to develop methods to study the production and release of monocytes from the bone marrow using the thymidine analog 5'-bromo-2'-deoxyuridine (BrdU) . Dividing monocytes in bone marrow were labeled with BrdU (MOBrdU), and their release into the blood and disappearance from the circulation were monitored using a double immunostaining method . The first MOBrdU appeared in the circulation 4 h after labeling with BrdU and peaked at 18 h when 34.3 +/- 5.8% of monocytes were labeled . The calculated transit time of monocytes through bone marrow was 38.1 +/- 3.1 h in control rabbits with a half-life (T1/2) of 12.7 h . Instillation of Streptococcus pneumoniae into the lung accelerated the release of monocytes from bone marrow (peak at 10 h) and shortened their bone marrow transit time (27.1 +/- 1.8 vs . 22.6 +/- 0.6, vehicle vs . pneumonia; P < 0.05) . We conclude that this nonradioisotope method provides a novel way to monitor monocyte kinetics and confirmed previous reports that a focal pneumonia shortens monocyte marrow transit and increases their release into the circulation.

FEMS Microbiol Lett, 2003 Mar 28, 220(2), 303 - 8
A solute binding protein of Streptococcus pneumoniae iron transport; Tai SS et al.; Streptococcus pneumoniae causes considerable morbidity and mortality throughout the world . Iron acquisition is an important virulence factor for bacterial pathogens . Two loci, piu and pia, were identified as responsible for the hemoglobin utilization of S . pneumoniae . The binding activity and surface accessibility of the solute binding protein of PiuA were studied . PiuA is a lipoprotein, binds hemin and hemoglobin, resides on the cytoplasmic membrane, and is not exposed on the surface of S . pneumoniae . The localization of PiuA has implications in its role in hemoglobin utilization and possible use as a pneumococcal vaccine.

FEMS Microbiol Lett, 2003 Mar 28, 220(2), 171 - 6
Assessment of the utilization of the antisense RNA strategy to identify essential genes in heterologous bacteria; Wang B et al.; We employed an antisense RNA approach to identify essential genes common in both Gram-positive and Gram-negative bacteria by cloning a random library of Streptococcus mutans chromosomal DNA into an expression vector and transforming Escherichia coli . Twelve out of 27 E . coli transformants with growth defective phenotypes contained individual structural genes of S . mutans in the antisense orientation relative to the E . coli promoter . Thirty-three percent of these transformants (4/12) corresponded to the genes (gyrA, ileS, rplE and yihA orthologs) which are essential for bacterial viability.

J Antimicrob Chemother, 2003 May, 51(5), 1247 - 52 Epub 2003 Mar 28.
Target site penetration of fosfomycin in critically ill patients; Joukhadar C et al.; OBJECTIVE: The present study was undertaken to investigate the target site penetration properties of fosfomycin, an antibiotic particularly suitable for treatment of soft tissue infections (STIs) in critically ill patients . METHODS AND RESULTS: The study population included nine patients with sepsis . Penetration of fosfomycin into the interstitial space fluid of skeletal muscle was measured using the microdialysis technique, following a single intravenous administration of 8.0 g of fosfomycin to patients . The median (range) fosfomycin area under the concentration versus time profile for plasma and skeletal muscle were 673 (459-1108) and 477 (226-860) mg x h/L (P < 0.011), respectively . Interstitial maximum concentrations were lower than plasma values (P < 0.029) . Median fosfomycin concentrations in the interstitium and plasma exceeded 70 mg/L throughout the observation period of 4 h and covered MICs for Streptococcus pyogenes, Staphylococcus aureus and Pseudomonas aeruginosa . Simulation of bacterial growth inhibition of S . pyogenes, based on tissue concentration data, confirmed the bactericidal properties of fosfomycin described in previous studies . CONCLUSION: Fosfomycin concentrations in muscle interstitium and plasma exceeded the MICs for a range of clinically relevant pathogens in critically ill patients . Thus, fosfomycin exhibits a tissue pharmacokinetic profile, which appears to offer an alternative to other broad-spectrum antibiotics in intensive care patients suffering from STI.

Microb Pathog, 2003 Apr, 34(4), 195 - 204
Differential expression of the enolase gene under in vivo versus in vitro growth conditions of Aeromonas hydrophila; Sha J et al.; Aeromonas hydrophila is an emerging human pathogen that leads to gastroenteritis and other invasive diseases . By using a murine peritoneal culture (MPC) model, we identified via restriction fragment differential display PCR (RFDDPCR) five genes of A . hydrophila that were differentially expressed under in vivo versus in vitro growth conditions . The gene encoding enolase was among those five genes that were differentially up regulated . Enolase is a glycolytic enzyme and its surface expression was recently shown to be important in the pathogenesis of a gram-positive bacterium Streptococcus pyogenes . By Western blot analysis and Immunogold staining, we demonstrated secretion and surface expression of enolase in A . hydrophila . We also showed that the whole cells of A . hydrophila had strong enolase activity . Using an enzyme-linked immunosorbant assay and sandwich Western blot analysis, we demonstrated binding of enolase to human plasminogen, which is involved in the fibrinolytic system of the host . We cloned the A . hydrophila enolase gene, which exhibited 62% homology at the DNA level and 57% homology at the amino acid level when compared to S . pyogenes enolase . This is a first report describing the increased expression of enolase gene in vivo that could potentially contribute to the pathogenesis of A . hydrophila infections .

Clin Microbiol Infect, 2003 Apr, 9(4), 280 - 8
Clinical and microbiological epidemiology of Streptococcus pneumoniae bacteremia in eight French counties; Maugein J et al.; OBJECTIVE: To describe the incidence of pneumococcal bacteremia not associated with infection of the central nervous system, investigate the susceptibility of bacterial isolates to beta-lactams, evaluate risk factors for antibiotic resistance, and determine factors predicting patient outcome . METHODS: Over a period of 1 year, 919 Streptococcus pneumoniae isolates were collected from 919 patients with bacteremia in eight French counties . Their clinical and microbiological features were recorded . Univariate and multivariate analyses were used to determine risk factors for penicillin-non-susceptible pneumococcal bacteremia and predictors of fatal outcome . RESULTS: Of the 919 patients in the study, 27% were infected with penicillin-non-susceptible pneumococci (PNSP): 17.8% of the isolates were intermediate to penicillin, 7.2% were resistant to penicillin, 16% were intermediate to amoxicillin, and 11% were intermediate to cefotaxime; no PNSP were resistant to either of the last two antibiotics . The most common PNSP serotypes isolated were 14 (41%) and 23 (24%) . A statistically significant relationship between PNSP infection and age below 5 years or above 60 years in the different counties was observed by univariate and multivariate analysis . Gender, origin of bacteremia, co-morbidity, immunodeficiency, previous hospitalization and nosocomial infection were not predisposing factors associated with PNSP . The mortality rate was 20.6%: there was no increase in mortality among patients with PNSP bacteremia . Age was the strongest risk factor for mortality, but immunodeficiency also seemed to have had an impact on mortality . Clinical outcome was more closely related to clinical conditions than to the susceptibility status of S . pneumoniae . CONCLUSION: Among cases of bacteremia, 27% were caused by PNSP, but this level varies according to the counties and the age of the patients . Infection-related mortality was high, but there was no increase related to penicillin G non-susceptibility of the infecting strain.

Orv Hetil, 2003 Feb 9, 144(6), 263 - 7
{Elevated level of Helicobacter pylori antibodies in Henoch-Schonlein purpura}; Novak J et al.; INTRODUCTION: Henoch-Schonlein purpura is a non-thrombocytopenic haemorrhagic syndrome characterized by deposition of immunocomplexes in the wall of the arterioles, capillaries and venules, involving the skin, joints, gastrointestinal mucosa, and glomeruli . Several causal factors could be responsible for its evaluation, however the exact exciting agent have not been identified yet . The Helicobacter pylori infection is suggested as a possible cause of Henoch-Schonlein purpura by some authors too (Gasparini and al: Eur J Gastroenterol, 1997, 9, 231-233) . AIM: Between 1995-2000 11 adult patients (64 +/- 10 year) suffering from Henoch-Schonlein purpura were admitted in our department taking particular care over detecting Helicobacter pylori infection . METHOD: Patients were classified as having either Henoch-Schonlein purpura in acute phase (5) or in remission phase (6) . Each patient underwent panendoscopy with 2-2 biopsies being taken from the corpus, antral and duodenal mucosa . It was investigated the type of inflammation and the existence of Helicobacter pylori . The authors studied laboratory and immunological profiles of all the patients . Previously non of the patients got eradication therapy . RESULT: The serological investigations revealed Helicobacter pylori infection in ten investigated patients . Patients in the acute phase had significantly higher level of anti H . pylori IgG (86 +/- 32 versus 32.5 +/- 23 U/ml) (p < 0.05) compared to remission . Anti H . pylori IgA were elevated with significant difference in remission phase (3.09 +/- 1.78 versus 1.96 +/- 0.58 ratio) (p < 00.5) . TNF-alpha level were significantly increased in acute phase (58.8 +/- 18 versus 27.3 +/- 5 pg/ml) (p < 0.001) . Serum IgA level were also significantly higher in acute phase (5.44 +/- 1.04 versus 3.49 +/- 1.14) (p < 0.05) . Anti Streptococcus DN-ase B were higher only in two patients . ANCA were negative in the all patients . CONCLUSION: According to authors findings the results suggest that seropositivity for Helicobacter pylori may be a risk factor for Henoch-Schonlein purpura . The causal role of Helicobacter pylori in the developing of Helicobacter pylori induced extraintestinal manifestations is equivocal however, it can not be ruled out with absolute certainty . To better understanding of this entity further clinical and experimental examinations have to be performed.

Ned Tijdschr Geneeskd, 2003 Mar 8, 147(10), 450 - 4
{Fulminant pneumococcal sepsis in two splenectomized patients}; de Vries PA et al.; Two 41-year-old women, who had previously been splenectomized, were admitted to the intensive-care unit due to fulminant sepsis . On admission, petechiae and ecchymoses characterised the clinical presentation of both patients . Laboratory tests revealed the presence of renal insufficiency and thrombocytopenia with disseminated intravascular coagulation . Streptococcus pneumoniae with serotypes (24 and 38) not included in the current polyvalent pneumococcal vaccine were found in blood cultures from both patients . One patient died as a result of a refractory septic shock . The other patient, who had never been vaccinated with the polyvalent pneumococcal vaccine, survived the sepsis . The clinical course of a fulminant Streptococcus pneumoniae sepsis in both asplenic patients underlines the importance of vaccination . It is also important to educate the patient about seeking immediate medical help if an infection is suspected on the basis of these symptoms . Vaccination does not provide complete protection.

Ned Tijdschr Geneeskd, 2003 Mar 8, 147(10), 425 - 8
{Missing spleen: indication for pneumococcal vaccination}; van Dijk GW et al.; Two female patients, aged 39 and 52 years, developed severe pneumococcal meningitis . Both patients had undergone splenectomy in the past (one after trauma and one for idiopathic thrombocytopenic purpura) and pneumococcal vaccination was only given immediately after the splenectomy . After antibiotic treatment and intensive care one patient remained disabled and the other patient died . There is a higher risk of developing severe sepsis after splenectomy, with Streptococcus pneumoniae being the causative micro-organism in more than 50% of cases . Vaccination after splenectomy in order to prevent a severe sepsis syndrome is very important . Indications for the 7 valent pneumococcal conjugate vaccine and the 23 valent polysaccharide vaccine are given.

Intensive Care Med, 2003 May, 29(5), 808 - 16 Epub 2003 Mar 29.
Streptococcus pneumoniae strain-dependent lung inflammatory responses in a murine model of pneumococcal pneumonia; Mohler J et al.; OBJECTIVE: The inherent properties of an invading bacterium may influence the cytokine profile that is ultimately produced . We determined the alterations in proinflammatory (TNF-alpha, IL-1, and IL-6) and anti-inflammatory cytokine (IL-10) expressions in lung tissues within the first 48 h after infection in mice with pneumonia induced by direct intratracheal inoculation of five different pneumococcal strains . DESIGN: Experimental murine model of Streptococcus pneumoniae pneumonia . SUBJECTS: Female BALB/cby mice aged 8-10 weeks . INTERVENTIONS: Five S . pneumoniae clinical isolates were used in this study . The strains included two serotype 3 strains (P4241 and P30606), two serotype 6 strains (P26772 and P23477), and one serotype 19 strain (P15986) . The trachea of anesthetized animals was cannulated via the mouth with a blunt needle, and 50 micro l bacterial suspension of two different inocula (their respective 100% lethal inoculum and the same 10(5) CFU/mouse inoculum of S . pneumoniae strains) were instillated . At predetermined times after pneumococcal infection, i.e., time 0 (preinfection) and 2, 4, 6, 12, 24, and 48 h postinfection in experimental groups, lung tissues were sampled from groups of three mice to quantify lung pro- and anti-inflammatory mediators . The experiments were repeated at least three times . RESULTS: Pneumonia induced by five different pneumococcal isolates resulted in pronounced differences in the local pro- and anti-inflammatory profiles . For example, with a 100% lethal inoculum of S . pneumoniae, the extent and timing of TNF-alpha expression varied greatly among strains, ranging from 2,643 to 10,022 pg/g and from 4 to 48 h, respectively . Moreover, TNF-alpha productions within 48 h postinfection measured by the 48 h area under the curve were differed significantly, ranging from 59,700 to 275,825 . These different profiles were not serotype dependent . Comparable results were obtained when IL-1, IL-6, and IL-10 expressions in lung tissues were studied . CONCLUSIONS: These findings confirm that the production of the pro- and anti-inflammatory mediators are critically dependent not only upon the different species of bacteria used to establish the experimental infection but also upon the different strains of a specific bacterial species used, i.e., S . pneumoniae in this study . These substantially different host responses were not serotype dependent . Moreover, the profile of lung pro-and anti-inflammatory cytokines within 48 h postinfection, at least in this pneumonia model, was not related to outcome of animals.

Ophthalmic Surg Lasers Imaging, 2003 Mar-Apr, 34(2), 128 - 30
Late-onset bacteria endophthalmitis following glaucoma drainage implantation; Francis BA et al.; A clinicopathologic report of late-onset bacterial endophthalmitis 4 years after implantation of a Baerveldt drainage implant is described . An 80-year-old woman with glaucoma presented 8 years after tube shunt implantation with clinical endophthalmitis . During surgical removal of the implant, a small conjunctival buttonhole caused by the suture securing the plate to the sclera was noted to be the only entry site . Vitreous and anterior chamber taps were performed with intravitreal antibiotics . Cultures revealed Streptococcus pneumoniae infection . The pathologic analysis showed epithelialization of the conjunctival button-hole and diffuse ocular inflammation, mucopurulent material, and fibrovascular membranes . Due to severe pain, the eye was enudeated after 1 week.

Health Bull (Edinb), 2001 Jul, 59(4), 263 - 7
A complete audit cycle of intrapartum group B streptococcus prophylaxis; McCord N et al.; INTRODUCTION: Group B Streptococcus (GBS) colonises the intestines of approximately one third of women and can result in intermittent colonisation of the vagina . The principal route of neonatal infection is from the vagina during delivery which can cause morbidity and mortality in the neonate . We recently introduced a protocol of intrapartum prophylaxis based on recognised risk factors . OBJECTIVE: To complete an audit cycle to determine the adequacy of intrapartum antibiotic prophylaxis for women with recognised risk factors for neonatal GBS infection, to make changes to the indications for prophylaxis and to highlight and rectify any deficiencies in practice . METHODS: Women identified with risk factors for neonatal GBS were treated with a regimen of intravenous benzylpenicillin or clindamycin . Adequate prophylaxis was achieved if the women received antibiotics more than four hours prior to delivery . The case notes of all deliveries over a four-week period were reviewed in both the initial audit and the re-audit . RESULTS: Three hundred and fifty nine deliveries occurred during the initial study period . Thirty seven (10.3%) women were identified with risk factors but adequate prophylaxis was provided to only 32% . Difficulty in providing adequate prophylaxis to women with intrapartum maternal pyrexia due to time constraints and an unanticipated increase in the number of neonates of 35 to 37 weeks gestation receiving postnatal intravenous antibiotics necessitated changes to the indications for prophylaxis . During the re-audit there were 378 deliveries with 49 (13%) women identified with risk factors and adequate prophylaxis was achieved in 42% of women . CONCLUSION: Despite changes to the protocol and circulation of the results to medical and midwifery staff, the percentage of women receiving adequate prophylaxis is low . Areas for further improvement include greater awareness of the indications for prophylaxis through education and better documentation of risk factors present before labour . Despite the benefits of adopting a protocol of intrapartum prophylaxis it is important to recognise its practical limitations and to continue to be vigilant in identifying and treating neonates whose mothers have not received adequate treatment.

Diagn Microbiol Infect Dis, 2003 Mar, 45(3), 153 - 64
The growth and survivability of Streptococcus pneumoniae clinical isolates subjected to various environmental conditions; Mazzola GJ et al.; Historically, it has been hypothesized that environmental stress would favor the survival of antibiotic susceptible bacteria over resistant ones; however, there is little direct evidence to support this theory . Clinical isolates of S . pneumoniae were chosen and categorized as: penicillin susceptible, quinolone susceptible (PSQS, n = 3); penicillin resistant, quinolone susceptible (PRQS, n = 3); and penicillin resistant, quinolone resistant (PRQR, n = 5) . Baseline growth of each isolate was measured by optical density for 24 h . The resulting optical density curves were compared to those obtained for the same isolates subjected to changes in environmental conditions, such as various temperature, pH, and diluted media . In addition, each isolate was inoculated onto cotton fiber disks, held at room temperature, and the recoverable CFU measured over 144 h . In comparison to controls grown under ideal conditions, the density of PSQS isolates was significantly lower than PRQR isolates after 24 h for the following conditions (p < 0.01): incubation at 40 degrees C (1.3 log10 lower); at pH 6.5 (1.6 log10 lower); and in limited nutrient conditions (1.36 log10 lower) . When inoculated onto cotton fiber disks, the PRQR isolates decreased an average of 5.0 log10 after 72 h as compared to controls . In contrast, PSQS isolates decreased an average of 8.1 log10 (p < 0.01) . Results of this study support the concept that antibiotic resistant isolates may not be at a competitive disadvantage in comparison to susceptible isolates when subjected to some adverse environmental conditions.

J Nat Prod, 2003 Mar, 66(3), 384 - 91
Bioactive sterols from the starfish Certonardoa semiregularis; Wang W et al.; Thirteen new polyhydroxysterols (1-5, 7-12, 14, 15) and two known polyhydroxysterols (6, 13) were isolated from the brine shrimp active fraction of the starfish Certonardoa semiregularis . The structures were determined on the basis of spectral analysis and chemical derivatization . These compounds displayed considerable cytotoxicity against a small panel of human solid tumor cell lines . These compounds were also evaluated for antibacterial activity against 20 clinically isolated strains . Most of the compounds showed weak antibacterial activity against Streptococcus pyogenes 308A, Pseudomonas aeruginosa 1771, and Pseudomonas aeruginosa 1771M.

Ann Clin Lab Sci, 2003 Winter, 33(1), 62 - 7
Nitric oxide-dependent regulation of pro-inflammatory cytokines in group B streptococcal inflammation of rat lung; Raykova VD et al.; Group B Streptococcus (GBS) infection leading to sepsis and lung injury is a major cause of neonatal morbidity and mortality . Lung injury may result from overproduction of pro-inflammatory mediators (cytokines), caused by nitric oxide (NO) . Our objective was to characterize the molecular signaling events involving the pro-inflammatory mediators interleukin-6 (IL-6) and macrophage inflammatory protein (MIP-2) in the presence of aminoguanidine (AG), an inducible nitric oxide synthase (iNOS) specific inhibitor, in lung tissue from GBS-treated young rats . Changes in iNOS mRNA, lactic acid, and rectal temperature were determined as markers of the inflammatory response . Expression and regulation of IL-6 and MIP-2 mRNA in lung tissue were studied by RT-PCR with densitometry analysis . GBS treatment of young rats induced the expression of pro-inflammatory mediators IL-6 (6-fold) and MIP-2 (3-fold) in lung tissue compared to controls . AG decreased IL-6 and MIP-2 expression . Addition of L-arginine (L-arg) reversed the AG effect on IL-6 and MIP-2 expression . These data suggest a role for the nitric oxide pathway in the overproduction of pro-inflammatory mediators IL-6 and MIP-2 during GBS-induced lung inflammation . This pathway may be responsible for the initiation of lung injury.

Ned Tijdschr Geneeskd, 2003 Mar 1, 147(9), 381 - 6
{Community acquired pneumonia; no reason to revise current Dutch antibiotic guidelines}; Oosterheert JJ et al.; Community-acquired pneumonia is an important cause of hospital admission and mortality in the adult population . The recommended antibiotic for pneumonia caused by Streptococcus pneumoniae is a beta-lactam antibiotic and, for so-called atypical pathogens, a macrolide . In the US and elsewhere, the current recommendation is to start with a beta-lactam antibiotic and a macrolide or with one of the new quinolones . The available literature consists largely of retrospective studies . Because of possible selection bias in these analyses and inconsistencies in reported outcomes, it is not possible to draw any well-founded conclusions from these studies . Reasons for a possible additional benefit of adding a macrolide to the therapy could include: a higher prevalence of undiagnosed atypical pathogens, the anti-inflammatory effects of macrolides, and resistance of the main pathogens against beta-lactam antibiotics . None of these appear to play a significant role . There is no need to revise Dutch guidelines.

Postepy Hig Med Dosw, 2002, 56 Suppl, 85 - 90
{The role of IVIG in treatment of generalized infections}; Lewandowicz-Uszynska A; In the research basing on data of literature we showed opinions on the subject of using IVIG in treatment of sepsis and of septic shock, especially in streptococcal toxic shock syndrome caused by Streptococcus pyogenes and Streptococcus pneumoniae.

J Infect Dis, 2003 Mar 15, 187(6), 1000 - 9 Epub 2003 Mar 06.
Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumoniae; McCullers JA et al.; A lethal synergism exists between influenza virus and Streptococcus pneumoniae, accounting for excess mortality during influenza epidemics . Using a model of viral-bacterial synergism, we assessed the role that the influenza virus neuraminidase (NA) has in priming mice for pneumococcal infection . Administration of the selective NA inhibitor oseltamivir improved survival, independent of viral replication and morbidity from influenza . Both pathologic examination of the lungs and live imaging of pneumonic lesions, using a bioluminescent pneumococcus, suggested that the effect of NA inhibition was to limit the extent of pneumococcal pneumonia during early infection . Adherence assays and immunohistochemical staining for sialic acids in lungs from infected mice demonstrated that the influenza virus NA potentiates development of pneumonia by stripping sialic acid from the lung, thus exposing receptors for pneumococcal adherence . Selective NA inhibitors may be useful clinically to interrupt this novel mechanism of synergism and to prevent excess mortality from secondary bacterial pneumonia.

Eur J Pharm Sci, 2003 Mar, 18(3-4), 267 - 77
Comparative characterization of bovine testicular hyaluronidase and a hyaluronate lyase from Streptococcus agalactiae in pharmaceutical preparations; Oettl M et al.; Although bovine testicular hyaluronidase (BTH) has been used in several medical fields for many years, these drugs are poorly characterized . We compared pharmaceutical BTH preparations (Neopermease, Hylase "Dessau") and a hyaluronate lyase from Streptococcus agalactiae . The BTH preparations were complex mixtures of proteins (SDS-PAGE, gel filtration) with enzymatic activity in different fractions . In the case of Neopermease the highest specific activity was found in the 58 kDa fraction (optimum at pH 3.6), whereas the 77 and 33 kDa fractions showed markedly lower specific activities at an optimal pH of 6.2 . Maximum specific activity of the bacterial enzyme (approx . 1000 micromol min(-1) mg(-1)) was found at pH 5.0, being 410- and 5100-times higher compared to Neopermease and Hylase "Dessau", respectively . The hyaluronate lyase preparation was separated into two main proteins {100 kDa (pI=8.9) and 85 kDa (pI=9.2)} which were enzymatically active in SDS substrate-PAGE . Zymography after limited proteolysis of the bacterial enzyme with trypsin revealed active fragments (75-50 kDa) . Our results suggest that hyaluronate lyase is an alternative for BTH, of which there has been a shortage, since companies have stopped the production of BTH preparations due to the risk of BSE.

Photochem Photobiol Sci, 2002 Feb, 1(2), 120 - 5
The photobleaching of disulfonated aluminium phthalocyanine in microbial systems; Lacey JA et al.; Front-face illumination spectroscopic techniques were used to study photobleaching of disulfonated aluminium phthalocyanine (AlPcS2) in the bacteria and yeast cells Escherichia coil, Porphyromonas gingivalis (Gram-negative bacteria), Streptococcus mutans (a Gram-positive bacterium), and the yeast Candida albicans . The photobleaching of AlPcS2 with the microbes studied is complex, involving reactive species generated by type I and type II processes with the rate dependent on the relative contributions of the different photobleaching mechanisms . The average rate of photobleaching of the AlPcS2 monomer in the presence of both E . coli and C . albicans increases as the fluence of the illumination source decreases . The effects of oxygen and sensitiser concentration on the rate of AlPcS2 photobleaching in these systems are also investigated.

Cornea, 2003 Apr, 22(3), 249 - 53
Efficacy of transport media use versus direct inoculation of blood agar plates in the microbiologic evaluation of experimental Streptococcus pneumoniae keratitis; Kuo IC et al.; PURPOSE: To compare the microbiologic yield of cultures obtained by direct inoculation of blood agar plates (BAP) from corneal ulcer swabbings versus indirect inoculation via transport media in a rabbit model of Streptococcus pneumoniae bacterial keratitis . METHODS: The corneas of 12 rabbits were inoculated with S . pneumoniae . Keratitis was confirmed 18 hours later . Sampling was performed at four 2.5-hour intervals . At each interval, corneal swabs were directly applied to BAP and placed into transport medium: thioglycollate and Amies medium without charcoal . Swabbings were then subcultured onto BAP at two time points: 2 and 24 hours after collection in transport medium . Plates were evaluated 48 hours later . Organism recovery rates were measured in terms of the number of positive culture plates observed and the bacterial colony counts on each plate . RESULTS: The rate of positive cultures overall was 69% . The recovery rates were similar for direct inoculation, inoculation via Amies held for 2 hours, and inoculation via Amies held for 24 hours . Direct inoculation yielded fewer colonies than indirect inoculation via Amies held for 24 hours (p = 0.008) . Direct inoculation yielded a higher rate of positive cultures than did thioglycollate held for 2 hours (p = 0.004) or 24 hours (p < 0.001) . The rate of nonpneumococcal contaminants ranged from 6% of BAP subcultured from thioglycollate held for 24 hours to 28% of directly inoculated BAP . CONCLUSIONS: Amies medium without charcoal may be used as a transport medium for up to 24 hours in the recovery of S . pneumoniae from corneal ulcers in this rabbit model . Thioglycollate appears to be less effective as a transport medium . Results of this study may justify studies of other transport media and/or other corneal pathogens . Altogether, such studies may provide justification for human clinical trials.

Acta Crystallogr D Biol Crystallogr, 2003 Apr, 59(Pt 4), 758 - 60 Epub 2003 Mar 25.
Cloning, overexpression, purification, crystallization and preliminary diffraction analysis of the receiver domain of MicA; Bent CJ et al.; MicA is a response regulator from Streptococcus pneumoniae thought to be involved in redox-energy sensing under oxygen-limiting environments . The purified protein was crystallized using the sitting-drop vapour-diffusion technique . X-ray diffraction data were collected using synchrotron radiation to a resolution of 1.91 A . The crystals belong to the monoclinic space group C222(1), with unit-cell parameters a = 78.69, b = 92.57, c = 37.16 A, alpha = beta = gamma = 90.0 degrees . The Matthews coefficient indicates that MicA crystallizes with one molecule in the asymmetric unit.

J Autoimmun, 2003 Mar, 20(2), 183 - 90
Selective depletion of Vbeta2+CD8+ T cells in peripheral blood from rheumatic heart disease patients; Carrion F et al.; Acute rheumatic fever (ARF) and its chronic valvular sequelae are the delayed consequence of a pharyngeal infection with group A Streptococcus (GAS) . Several GAS proteins have been shown to be superantigens, raising the possibility that the expansion or deletion of T cells expressing specific Vbeta regions might play a role in the pathogenesis of ARF or chronic rheumatic heart disease (RHD) . We therefore analyzed by four-color flow cytometry, the Vbeta repertoire on CD3, CD4 and CD8 T cells from four ARF patients, 10 RHD patients and also nine healthy controls . A selective depletion of Vbeta2+ T cells was found only in the CD8 subset of chronic RHD patients . This is of interest since a number of GAS superantigens exert their effects on Vbeta2+ cells and because only CD8+ T cells from ARF and RHD patients undergo anergy in response to GAS superantigens . Our results suggests that an ongoing immune process is present in RHD patients and that CD8+ T cells may have an important immunoregulatory role in the pathogenesis of the disease.

Int J Syst Evol Microbiol, 2003 Jan, 53(Pt 1), 143 - 6
Emended description of Streptococcus ferus isolated from pigs and rats; Baele M et al.; Streptococcus ferus is a mutans-like streptococcus originally isolated from wild rats fed with sugar cane . Taxonomically, this species has not been studied extensively . Ten Gram-positive coccal strains, isolated from the tonsils and nasal conchae of piglets, were identified as S . ferus by 16S rDNA sequencing, tRNA-intergenic spacer length polymorphism analysis (tDNA-PCR), whole-cell protein profiling using SDS-PAGE, G+C content determination and extensive biochemical testing . In all these tests, the type strain of S . ferus (LMG 16520T), from a rat, was included . The results of the tests are described and an emended species description is presented.

Infect Immun, 2003 Apr, 71(4), 2199 - 207
Group A Streptococcus gene expression in humans and cynomolgus macaques with acute pharyngitis; Virtaneva K et al.; The molecular mechanisms used by group A Streptococcus (GAS) to survive on the host mucosal surface and cause acute pharyngitis are poorly understood . To provide new information about GAS host-pathogen interactions, we used real-time reverse transcription-PCR (RT-PCR) to analyze transcripts of 17 GAS genes in throat swab specimens taken from 18 pediatric patients with pharyngitis . The expression of known and putative virulence genes and regulatory genes (including genes in seven two-component regulatory systems) was studied . Several known and previously uncharacterized GAS virulence gene regulators were highly expressed compared to the constitutively expressed control gene proS . To examine in vivo gene transcription in a controlled setting, three cynomolgus macaques were infected with strain MGAS5005, an organism that is genetically representative of most serotype M1 strains recovered from pharyngitis and invasive disease episodes in North America and Western Europe . These three animals developed clinical signs and symptoms of GAS pharyngitis and seroconverted to several GAS extracellular proteins . Real-time RT-PCR analysis of throat swab material collected at intervals throughout a 12-day infection protocol indicated that expression profiles of a subset of GAS genes accurately reflected the profiles observed in the human pediatric patients . The results of our study demonstrate that analysis of in vivo GAS gene expression is feasible in throat swab specimens obtained from infected human and nonhuman primates . In addition, we conclude that the cynomolgus macaque is a useful nonhuman primate model for the study of molecular events contributing to acute pharyngitis caused by GAS.

Infect Immun, 2003 Apr, 71(4), 2087 - 94
Pneumolysin-dependent and -independent gene expression identified by cDNA microarray analysis of THP-1 human mononuclear cells stimulated by Streptococcus pneumoniae; Rogers PD et al.; Pneumolysin is an important virulence factor of Streptococcus pneumoniae, interacting with the membranes of host cells to elicit a multitude of inflammatory responses . We used cDNA microarrays to identify genes which are responsive to S . pneumoniae in a pneumolysin-dependent and -independent fashion . The THP-1 human monocytic cell line was coincubated for 3 h with medium alone, with the virulent type 2 S . pneumoniae strain D39, or with the isogenic strain PLN, which does not express pneumolysin . RNA was isolated from the monocytes and hybridized on cDNA microarrays . Of 4,133 genes evaluated, 142 were found to be responsive in a pneumolysin-dependent fashion, whereas 40 were found to be responsive independent of pneumolysin . Genes that were up-regulated in cells exposed to D39 relative to those exposed to PLN included genes encoding proteins such as mannose binding lectin 1, lysozyme, alpha-1 catenin, cadherin 17, caspases 4 and 6, macrophage inflammatory protein 1beta (MIP-1beta), interleukin 8 (IL-8), monocyte chemotactic protein 3 (MCP-3), IL-2 receptor beta (IL-2Rbeta), IL-15 receptor alpha (IL-15Ralpha), interferon receptor 2, and prostaglandin E synthase . Down-regulated genes included those encoding complement component receptor 2/CD21, platelet-activating factor acetylhydrolase, and oxidized low-density lipoprotein receptor 1 (OLR1) . Pneumolysin-independent responses included down-regulation of the genes encoding CD68, CD53, CD24, transforming growth factor beta2, and signal transducers and activators of transcription 1 . These results demonstrate the striking effects of pneumolysin on the host cell upon exposure to S . pneumoniae.

Infect Immun, 2003 Apr, 71(4), 2009 - 13
Effects of zinc deficiency and pneumococcal surface protein a immunization on zinc status and the risk of severe infection in mice; Strand TA et al.; Streptococcus pneumoniae is a major cause of illness and death in children in developing countries . In these children, zinc deficiency is associated with an increased risk of acute respiratory tract infections, which can be reduced by daily zinc administration . Severe infections decrease zinc levels in plasma and may thereby move individuals with preexisting low zinc stores into a vicious cycle of infection and unavailable zinc . Pneumococcal surface protein A (PspA) has emerged as a promising vaccine candidate, and immunization with this antigen protects animals from pneumococcal infection . In an animal experiment, we measured the effect of zinc depletion on the immune response to parenterally administrated PspA and assessed the effect of this PspA vaccination and zinc depletion on the severity of pneumococcal infection and on zinc status . Mice were kept on different diets for 5 weeks, immunized twice 14 days apart, and challenged intranasally with S . pneumoniae . Mice on the zinc-deficient diet showed substantially reduced immune responses to PspA, more extensive pneumococcal colonization in the nasal mucosa, more severe infections, and an increased risk of death . PspA immunization reduced the risk of severe disease, and the reduction in severity was reflected in substantially reduced zinc depletion from bones.

Infect Immun, 2003 Apr, 71(4), 1938 - 43
The stress-responsive dgk gene from Streptococcus mutans encodes a putative undecaprenol kinase activity; Lis M et al.; We analyzed a previously constructed stress-sensitive Streptococcus mutans mutant Tn-1 strain resulting from disruption by transposon Tn916 of a gene encoding a protein exhibiting amino acid sequence similarity to the Escherichia coli diacylglycerol kinase . It was confirmed that the mutation led to significantly reduced lipid kinase activity, while expression of the intact gene on a plasmid restored both kinase activity and the wild-type phenotype . Further analysis revealed that the product of the dgk gene in S . mutans predominantly recognizes a lipid substrate other than diacylglycerol, most likely undecaprenol, as demonstrated by its efficient phosphorylation and the resistance of the product of the reaction to saponification . The physiological role of the product of the dgk gene as a putative undecaprenol kinase was further supported by a significantly higher sensitivity of the mutant to bacitracin compared with that of the parental strain.

Infect Immun, 2003 Apr, 71(4), 1813 - 9
Pneumococcal behavior and host responses during bronchopneumonia are affected differently by the cytolytic and complement-activating activities of pneumolysin; Jounblat R et al.; Pneumolysin, a multifunctional toxin produced by all clinical isolates of Streptococcus pneumoniae, is strongly implicated in the pathogenesis of pneumococcal bronchopneumonia and septicemia . Using isogenic mutant strains, we examined the effect of deletion of the cytotoxic activity or complement-activating activity of pneumolysin on bacterial growth in lungs and blood, histological changes in infected lung tissue, and the pattern of inflammatory cell recruitment . Both of the activities of pneumolysin contributed to the pathology in the lungs, as well as the timing of the onset of bacteremia . Histological changes in the lungs were delayed after infection with either mutant compared to the changes seen after infection with the wild-type pneumococcus . The complement-activating activity of pneumolysin affected the accumulation of T cells, whereas the toxin's cytolytic activity influenced neutrophil recruitment into lung tissue.

J Antimicrob Chemother, 2003 Apr, 51(4), 947 - 55 Epub 2003 Mar 13.
Community-acquired respiratory tract infections caused by resistant pneumococci: clinical and bacteriological efficacy of the ketolide telithromycin; Fogarty CM et al.; The incidence of community-acquired respiratory tract infections caused by Streptococcus pneumoniae exhibiting antibacterial resistance has increased dramatically in recent years . Telithromycin is the first of a new class of antibacterials, the ketolides, which have been developed specifically to provide effective treatment for these infections . Data were analysed from 3935 patients who had participated in one Japanese Phase II study and 11 US/global Phase III studies in three indications: community-acquired pneumonia, acute exacerbations of chronic bronchitis or acute sinusitis . Patients received either telithromycin 800 mg once daily or a comparator antibacterial . S . pneumoniae isolates considered to be causative for infection were tested for susceptibility to penicillin G and erythromycin A . In per-protocol analyses, telithromycin showed a high level of clinical efficacy against S . pneumoniae, with clinical cure rates of 92.8% for all isolates, 91.7% for those with reduced susceptibility to penicillin G and 86.0% for those with reduced susceptibility to erythromycin A . Bacterial eradication rates were consistent with the clinical outcomes . High rates of clinical cure and bacterial eradication were also observed for infections caused by isolates demonstrating high-level resistance to erythro-mycin A {MICs >/= 512 mg/L: 100% (13/13) clinical cure, 100% (13/13) bacterial eradication} . These results support the use of telithromycin as a first-line oral therapy for the treatment of community-acquired respiratory tract infections caused by S . pneumoniae with reduced susceptibility to penicillin G and erythromycin A.

J Antimicrob Chemother, 2003 Apr, 51(4), 905 - 11 Epub 2003 Mar 13.
AUC(0-t)/MIC is a continuous index of fluoroquinolone exposure and predictive of antibacterial response for Streptococcus pneumoniae in an in vitro infection model; Zelenitsky SA et al.; OBJECTIVE: To conduct a comprehensive pharmacodynamic analysis of moxifloxacin and levofloxacin against Streptococcus pneumoniae in an in vitro infection model . METHODS: In dose escalation studies, single doses with peak concentrations equivalent to 1 x, 2 x, 4 x, 8 x, 16 x and 32 x MIC against two isolates of S . pneumoniae were studied over 24 h . Traditional pharmacodynamic indices, including peak concentration divided by MIC (peak/MIC), time of concentration above MIC (T > MIC) and AUC24/MIC, were estimated for all regimens . As a continuous index of fluoroquinolone exposure, AUC0-t/MIC was also calculated, as AUC from time 0 to 1, 2 and 6 h divided by MIC . Correlations between pharmacodynamic indices and antibacterial effects were examined using linear and non-linear methods . In validation experiments, the pharmacodynamic model was used to predict bacterial kill curves, produced by simulated clinical doses of moxifloxacin and levofloxacin against two other S . pneumoniae isolates . RESULTS: Peak/MIC was most predictive of early bacterial kill, whereas T > MIC was significantly associated with final bacterial counts at 24 h . Antibacterial effects were bacteriostatic when T > MIC was 48% and bactericidal when values exceeded 55% . AUC0-t/MIC was strongly associated with bacterial kill throughout the dosing interval . Bactericidal activity and bacterial eradication were associated with AUC0-t/MICs of 28 and 135, respectively . AUC0-t/MIC was also highly predictive of bacterial kill curves produced by simulated clinical doses of moxifloxacin and levofloxacin (precision 0.36 log10 cfu/mL, bias 0.02 log10 cfu/mL) . CONCLUSION: This study demonstrated the novel application of AUC0-t/MIC as a continuous index of antibiotic activity, and provided extensive characterization of fluoroquinolone pharmacodynamics against S . pneumoniae.

J Antimicrob Chemother, 2003 Apr, 51(4), 939 - 45 Epub 2003 Feb 25.
Comparative distribution of azithromycin in lung tissue of patients given oral daily doses of 500 and 1000 mg; Danesi R et al.; OBJECTIVES: The administration of antibacterial agents should be optimized on the basis of their distribution to enhance drug exposure and obtain bacterial eradication . This study examines the pharmacokinetics of azithromycin in plasma, lung tissue and bronchial washing in patients after oral administration of 500 mg versus 1000 mg once daily for 3 days . PATIENTS AND METHODS: Samples of plasma, lung tissue and bronchial washing were obtained from a cohort of 48 patients during open-chest surgery for lung resection up to 204 h after the last drug dose, and assayed for antibiotic concentrations . RESULTS: Azithromycin was widely distributed within the lower respiratory tract and sustained levels of the drug were detectable at the last sampling time in lung tissue . Doubling the dose of the antibiotic resulted in a proportional increase in lung area under the curve (AUC, 1245.4 versus 2514.2 h x mg/kg) and peak tissue concentration (Cmax, 8.93 +/- 2.05 versus 18.6 +/- 2.20 mg/kg) . The pharmacodynamic parameter AUC/MIC for susceptible and intermediate strains of Streptococcus pneumoniae (MICs 0.5 and 2 mg/L, respectively) increased after administration of the 1000 mg schedule compared with 500 mg (AUC/MIC0.5 2414 versus 1144 and AUC/MIC2 2112 versus 814.1 h x mg/kg, respectively) in pulmonary tissue . CONCLUSIONS: Lung exposure to azithromycin is increased proportionally by doubling the dose, which results in a predictable pharmacokinetic behaviour of the drug in the lower respiratory tract.

J Antimicrob Chemother, 2003 Apr, 51(4), 887 - 93 Epub 2003 Mar 13.
Antibiotic susceptibility and serotypes of Streptococcus pneumoniae isolates from Hungary; Dobay O et al.; OBJECTIVE: Hungary has reported one of the highest incidences of penicillin resistance in Streptococcus pneumoniae in Europe since the 1970s and is still cited accordingly . However, since the end of the 1990s the resistance of pneumococci in Hungary has not been investigated . In this study we assessed the current situation, particularly to establish whether the incidence of resistance is increasing and if this could be related to the spread of specific strain types . METHODS: Isolates of S . pneumoniae (n = 304) were collected by five diagnostic laboratories in Hungary in 2000-2002 . Their identity was confirmed and their susceptibilities to 16 antibiotics were determined by the agar dilution method according to NCCLS guidelines . Representative strains were serotyped (n = 112) . RESULTS AND CONCLUSIONS: We found significantly lower resistance rates for penicillin compared with the data previously reported from Hungary, but the intermediate resistance was high, at 37% . Macrolide resistance was a bigger problem ( approximately 40% for erythromycin), although there was full susceptibility to telithromycin . The strains with the highest MICs were isolated from carriers and young children . The fluoroquinolones were very effective, especially moxifloxacin and gatifloxacin . There was full susceptibility to vancomycin and linezolid . We found inconsistencies with previous reports in the survey of the resistance and identification of S . pneumoniae in the country . The serotype distribution of the isolates showed a much greater diversity than had previously been reported; however, there was correlation between serotype and resistance.

Antimicrob Agents Chemother, 2003 Apr, 47(4), 1464 - 7
Frequency of mutation to rifampin resistance in Streptococcus pneumoniae clinical strains: hexA and hexB polymorphisms do not account for hypermutation; Morosini MI et al.; The frequency of mutation to rifampin resistance of 200 clinical Streptococcus pneumoniae isolates was examined . Two peaks were observed in the distribution, with mode frequencies of 2.5 x 10(-7) (20% of isolates) and 2.5 x 10(-8) . The hexA and hexB gene entire sequences were analyzed in 13 isolates . Sequences from both hypermutable and "normomutable" strains were conserved relative to that of the R6 S . pneumoniae control strain . The phenotypic Hex system proficiency, in terms of transforming efficiency, was also maintained irrespective of the variations in mutation frequency values.

Antimicrob Agents Chemother, 2003 Apr, 47(4), 1456 - 9
PCR-oligonucleotide ligation assay for detection of point mutations associated with quinolone resistance in Streptococcus pneumoniae; Bui MH et al.; We have developed a PCR-oligonucleotide ligation assay to rapidly identify base substitutions in topoisomerase genes that are associated with quinolone resistance in clinical isolates of Streptococcus pneumoniae . Thirty-seven strains for which the ciprofloxacin MICs were >/=4 micro g/ml and 16 strains for which the MICs were </=2 micro g/ml were assayed . Compared with sequence data, the assay correctly identified the DNA bases that encoded amino acids at the four positions most commonly associated with quinolone resistance (Ser79 and Asp83 of ParC and Ser81 and Glu85 of GyrA) . Therefore, this procedure can rapidly distinguish single base substitutions associated with quinolone-resistant topoisomerases in S . pneumoniae.

Antimicrob Agents Chemother, 2003 Apr, 47(4), 1433 - 5
Molecular characterization and antimicrobial susceptibility of fluoroquinolone-resistant or -susceptible Streptococcus pneumoniae from Hong Kong; Morrissey I et al.; Fluoroquinolone resistance in Streptococcus pneumoniae isolated from Hong Kong as part of Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin 1999/2000 was found to be due to the spread of the Spain(23F)-1 clone (mainly a Spain(23F)-1-14 variant) . All the isolates were multidrug resistant but were susceptible to quinupristin-dalfopristin, linezolid, and telithromycin . The Spain(23F)-1 clone also occurred among antimicrobial-susceptible isolates, which suggests that the primary source of this clone may have been Asia rather than Iberia.

Antimicrob Agents Chemother, 2003 Apr, 47(4), 1419 - 22
Genetic characterization of fluoroquinolone-resistant Streptococcus pneumoniae strains isolated during ciprofloxacin therapy from a patient with bronchiectasis; de la Campa AG et al.; Five Spain(9V-3) Streptococcus pneumoniae strains were isolated from a patient with bronchiectasis who had received long-term ciprofloxacin therapy . One ciprofloxacin-susceptible strain was isolated before treatment, and four ciprofloxacin-resistant strains were isolated during treatment . The resistant strains were derived from the susceptible strain either by a parC mutation (low-level resistance) or by parC and gyrA mutations (high-level resistance) . This study shows that ciprofloxacin therapy in a patient colonized by susceptible S . pneumoniae may select fluoroquinolone-resistant mutants.

Antimicrob Agents Chemother, 2003 Apr, 47(4), 1355 - 63
Pharmacokinetics and efficacy of linezolid in a gerbil model of Streptococcus pneumoniae-induced acute otitis media; Humphrey WR et al.; The oxazolidinone linezolid represents a new antibacterial class of potential benefit in managing multidrug-resistant gram-positive infections, including those caused by Streptococcus pneumoniae . In a gerbil model of acute otitis media (AOM) induced by either penicillin-resistant S . pneumoniae (PRSP; amoxicillin MIC = 8 micro g/ml, linezolid MIC = 1 micro g/ml) or penicillin-susceptible S . pneumoniae (PSSP; amoxicillin MIC = 0.015 micro g/ml, linezolid MIC = 1 micro g/ml), we explored the plasma and ear fluid levels of linezolid required to demonstrate efficacy . Threshold pathogen doses required to induce bilateral AOM (1,500 CFU/ear with PRSP; 30 CFU/ear with PSSP) were administered to gerbils by intrabullar injection on day 0 . At peak infection ( approximately 10(6) to 10(7) CFU/ear flush; day 2 for PRSP-AOM and day 3 for PSSP-AOM), twice-a-day oral doses of linezolid, amoxicillin, or vehicle were administered over 4.5 days prior to collection and assay of middle ear effluents for S . pneumoniae content . Linezolid doses of >/=10 mg/kg of body weight induced significant cure rates of >/=72% versus both PRSP and PSSP infections, whereas amoxicillin at </=100 mg/kg was consistently effective only versus PSSP-AOM . Plasma and ear fluid levels of linezolid necessary to elicit pneumococcal eradication from the middle ear were measured by high-performance liquid chromatography-tandem mass spectrometry and found to be similar both within and between each infection protocol . The plasma-ear fluid pharmacodynamic profile associated with linezolid efficacy was a T>MIC of >/=42%, a C(max)/MIC ratio of >/=3.1, and a (24-h area under the curve)/MIC ratio of >/=30 h . Application of this model will be useful in defining preclinical pharmacodynamic relationships of novel antibiotics necessary to cure S . pneumoniae-induced AOM.

Antimicrob Agents Chemother, 2003 Apr, 47(4), 1313 - 7
Rifampin followed by ceftriaxone for experimental meningitis decreases lipoteichoic acid concentrations in cerebrospinal fluid and reduces neuronal damage in comparison to ceftriaxone alone; Gerber J et al.; Rifampin (RIF) releases smaller quantities of lipoteichoic acids (LTAs) from Streptococcus pneumoniae than ceftriaxone (CRO) . Due to the rapid development of resistance, RIF cannot be used as a single agent for therapy of bacterial meningitis . For this reason, we compared the effect of treatment with RIF followed by treatment with CRO (RIF-CRO) or the effect of treatment with clindamycin (CLI) followed by treatment with CRO (CLI-CRO) to that of CRO alone on the concentrations of LTAs and teichoic acids in vitro . The effects of RIF-CRO on LTA concentrations in cerebrospinal fluid (CSF) and on neuronal injury were investigated in a rabbit model of S . pneumoniae meningitis . In vitro, bacterial titers were effectively reduced by CRO, RIF-CRO, and CLI-CRO when each drug was used at 10 micro g/ml . The levels of release of LTAs after the initiation of therapy were lower in RIF-CRO- and CLI-CRO-treated cultures than in cultures treated with CRO alone (P < 0.05 from 3 to 12 h after initiation of treatment) . Similarly, in rabbits, the increase in the amount of LTAs in CSF was lower in RIF-CRO-treated animals than in CRO-treated animals (P = 0.02) . The density of dentate apoptotic granular cells was lower after RIF-CRO therapy than after CRO therapy (medians, 58.4 and 145.6/mm(2), respectively; 25th quartiles, 36.3 and 81.7/mm(2), respectively; 75th quartiles, 100.7 and 152.3/mm(2), respectively; P = 0.03) . Therefore, initiation of therapy with a protein synthesis-inhibiting antibacterial and continuation of therapy with a combination that includes a beta-lactam may be a strategy to decrease neuronal injury in bacterial meningitis.

Antimicrob Agents Chemother, 2003 Apr, 47(4), 1257 - 61
High-efficiency generation of antibiotic-resistant strains of Streptococcus pneumoniae by PCR and transformation; Martin-Galiano AJ et al.; We designed a method by which to generate antibiotic-resistant strains of Streptococcus pneumoniae at frequencies 4 orders of magnitude greater than the spontaneous mutation rate . The method is based on the natural ability of this organism to be genetically transformed with PCR products carrying sequences homologous to its chromosome . The genes encoding the targets of ciprofloxacin (parC, encoding the ParC subunit of DNA topoisomerase IV), rifampin (rpoB, encoding the beta subunit of RNA polymerase), and streptomycin (rpsL, encoding the S12 ribosomal protein) from susceptible laboratory strain R6 were amplified by PCR and used to transform the same strain . Resistant mutants were obtained with a frequency of 10(-4) to 10(-5), depending on the fidelity of the DNA polymerase used for PCR amplifications . Ciprofloxacin-resistant mutants, for which the MICs were four-to eightfold higher than that for R6, carried a single mutation of a residue in the quinolone resistance-determining region: S79 (change to A, F, or Y) or D83 (change to N or V) . Rifampin-resistant strains, for which the MICs were at least 133-fold higher than that for R6, contained a single mutation within cluster I of rpoB: S482 (change to P), Q486 (change to L), D489 (change to V), or H499 (change to L or Y) . Streptomycin-resistant mutants, for which the MICs were at least 64-fold higher than that for R6, carried a mutation at either K56 (change to I, R, or T) or K101 (change to E) . PCR products obtained from the mutants were able to transform R6 to resistance with high efficiency (>10(4)) . This method could be used to efficiently obtain resistant mutants for any drug whose target is known.

J Dent, 2003 Feb, 31(2), 111 - 6
Comparison of antibacterial activity of two dentin bonding systems using agar well technique and tooth cavity model; Ozer F et al.; Objective . This study compared the antibacterial activities of two dentin bonding systems (ABF, Kuraray and Reactmer Bond, Shofu) by a conventional agar well technique and a newly designed in vitro test using tooth model.Methods . In the agar well technique, the test materials were filled in the wells of Muller Hinton agar plates inoculated with Streptococcus mutans NCTC10449, and the diameters of inhibition zones produced around the materials were measured after 24h of incubation . For the tooth model test, three cavities (diameter 1mm, depth 2mm) were prepared in the flat occlusal dentin of human extracted molar . After sterilization, the teeth were left in broth culture of 1.56x10(8)CFU/ml of S . mutans at 37 degrees C for 72h for allowing bacteria to invade the cavity . The dentin bonding systems were applied separately to each of the two infected cavities, and the third cavity was left unapplied for control . After sealing the occlusal surfaces, the teeth were kept in physiologic saline solution at 37 degrees C for 72h . The standardized amounts of dentin chips (120+/-5mg) were obtained from the cavity walls and the number of bacteria recovered was determined . The results were analyzed by One Way ANOVA, Kruskal Wallis and Mann-Whitney's U tests.Results . The primer of ABF and Reactmer Bond produced inhibition zones with similar sizes (p>0.05), but the bonding resin of ABF did not produce any inhibition . When tested by the model cavity method, the application of ABF resulted in significantly less bacterial recovery than Reactmer Bond (p<0.05), demonstrating substantial antibacterial effects.Conclusions . The tooth model method used in this study was effective for evaluating the substantial antibacterial effects of dentin bonding agents, and the experimental dentin bonding system ABF was demonstrated to be able to inactivate the bacteria in the cavity effectively in comparison with little antibacterial activity shown by Reactmer Bond.

Mikrobiyol Bul, 2002 Apr, 36(2), 125 - 31
{Streptococcus pneumoniae strains resistance to macrolide, lincosamide, streptogramin, oxazolidinone and ketolide}; Sener B et al.; Over the last two decades, antimicrobial resistance in Streptococcus pneumoniae has been detected at an increasing rate . There have been several reports of increasing rate of macrolide resistance among the penicillin-resistant S . pneumoniae strains . The rapid evolution of such resistance necessitated new antimicrobials, such as streptogramins, oxazolidinones and ketolides, against beta-lactam and macrolide resistant pneumococci . This study was undertaken to determine the prevalence of macrolide resistance in pneumococci isolated in a Turkish University hospital and also to determine the activity of these newly developed agents against pneumococci . For that purpose a total of 264 pneumococci, isolated from clinical specimens, were tested for susceptibility against penicillin, erythromycin, clarithromycin, clindamycin, quinupristin/dalfopristin, linezolid and telithromycin by agar dilution method . Penicillin resistance and intermediate penicillin resistance was found in 7.6% and 40% of isolates respectively, while resistance rates of the tested isolates against erythromycin, clarithromycin and clindamycin were as 15.9%, 13.6% and 13.6%, respectively . Resistance to macrolides and clindamycin was higher among the penicillin-resistant isolates . No resistance was detected against quinupristin/dalfopristin, linezolid and telithromycin, except for four strains which had minimal inhibitory concentration (MIC) values of intermediately susceptible category to quinupristin/dalfopristin . These data indicate the presence of an important percentage of macrolide resistant pneumococci in our hospital . It can also be concluded that streptogramins, oxazolidinones and ketolides may be used as good alternatives especially in case of infections due to macrolide resistant pneumococci.

Caries Res, 2003 Mar-Apr, 37(2), 148 - 56
Chromosomal insertions and deletions in Streptococcus mutans; Robinson WG et al.; Many isolates of Streptococcus mutans lack the ability to ferment melibiose and other sugars . We previously reported that this was commonly due to a chromosomal deletion and, in the present study, sequence information from the S . mutans genome project was used to design PCR primers to explore the nature and extent of the deletion . In all melibiose-negative strains examined, there was an incomplete insertion element, ISSmu3, in place of the 18-kb stretch of chromosome encoding the msm and GAL operons . Strains that were also unable to utilise beta-glucosides were found to have a separate 4 kb deletion in the BGL regulon that is proposed to be due to homologous recombination between two short stretches of identical sequence . The evidence is consistent with all the melibiose-negative strains examined being derived from a common ancestor .

Caries Res, 2003 Mar-Apr, 37(2), 79 - 84
Dental caries related to plasma IgG and alpha1-acid glycoprotein; de Soet JJ et al.; This study was aimed at determining whether dental caries is associated with induction of the systemic immune system or cytokine response . For this purpose, 85 children from Den Pasar, Bali, Indonesia, aged 6-7 years, were examined clinically and blood plasma was obtained via finger puncture . The concentrations of the acute-phase protein alpha(1)-acid glycoprotein (AGP), total IgG and the specific IgG and IgM immunoglobulins against Streptococcus mutans were determined . Immunoelectrophoresis was used for the determination of the AGP concentration and ELISA for IgG and IgM detection . The mean dmft of the whole group was 8.8 +/- 2.9, the mean number of infected pulps was 3.9 +/- 2.2 and the mean number of abscesses was 0.5 +/- 0.8 . The plasma concentration of AGP ranged between 0.13 and 1.6 mg/ml serum (mean 0.86 +/- 0.26 mg/ml) . Stepwise regression analysis revealed that the concentration of IgG against S . mutans (log-transformed) was significantly correlated with dmft (adjusted r(2) = 0.083, standardized beta coefficient = 0.31, p = 0.008) . When the concentration AGP was included in the model the correlation improved significantly (for IgG: adjusted r(2) = 0.157, standardised beta coefficient = 0.36, p = 0.002; for AGP: beta coefficient = -0.30, p = 0.009) . The results suggest a relationship between caries and systemic parameters of inflammation . On the basis of this, severe caries might have consequences on the general health of the subject .

Arch Dis Child, 2003 Apr, 88(4), 324 - 6
Vulvovaginitis in prepubertal girls; Stricker T et al.; This retrospective study evaluated the clinical features and findings in bacterial cultures and in microscopic examination of vaginal secretions in 80 prepubertal girls, aged 2-12 years, with vulvovaginitis . Vaginal secretions were obtained directly from the vagina with a sterile catheter carefully inserted into the vagina . Pathogenic bacteria were isolated in 36% of cases . In 59% of these cases the isolated pathogen was group A beta-haemolytic streptococcus . Candida was not found in any of the patients . The finding of leucocytes in vaginal secretions as an indicator for growth of pathogenic bacteria had a sensitivity of 83% and a specificity of 59% . Antimicrobial treatment should therefore be based on bacteriological findings of vaginal secretions and not on the presence of leucocytes alone.

Eur J Clin Microbiol Infect Dis, 2003 Mar, 22(3), 151 - 7 Epub 2003 Mar 05.
Factors associated with complications and mortality in adult patients hospitalized for infectious cellulitis; Carratala J et al.; The aim of this study was to analyze medical outcomes, including risks for complications and mortality, in 332 adult patients hospitalized for cellulitis . The infection was documented microbiologically in 128 cases (39%) . Staphylococcus aureus (46 cases) and Streptococcus pyogenes (22 cases) were the most frequent causative pathogens . Overall, 63 patients (19%) were discharged early (< or =4 days) and 166 patients (50%) were hospitalized for more than 4 days without developing any complications . One hundred three patients (31%) had one or more complications or died . Of these, 78 required surgical debridement, 10 required plastic surgery, 7 underwent amputation, and 15 had shock on presentation . When comparing the three study groups (patients discharged early, patients hospitalized for < or =4 days without complications, and patients who developed 1 or more complication or who died), patients who were discharged early (low risk) were more frequently female and were less likely to have multiple comorbid conditions, hypoalbuminemia, renal insufficiency, and/or cutaneous necrosis at presentation . Overall mortality (<30 days) was 5% (16/332 patients) . Factors associated with death were male sex, presence of multiple comorbid conditions, congestive heart failure, morbid obesity, hypoalbuminemia, renal insufficiency, shock, and Pseudomonas aeruginosa cellulitis . These findings can be used to stratify patients with acute cellulitis according to risks for complications and mortality and may be helpful when deciding the most appropriate means of care, i.e . outpatient treatment or hospitalization.

J Ethnopharmacol, 2003 Feb, 84(2-3), 181 - 5
Kuwanon G: an antibacterial agent from the root bark of Morus alba against oral pathogens; Park KM et al.; Kuwanon G was isolated from the ethyl acetate fraction of methanol extract of Morus alba and its structure was elucidated by 13C-NMR, 1H-NMR and FAB-MS . Antibacterial activity of kuwanon G was investigated by the minimum inhibitory concentration (MIC) test and the viable cell count method . MIC of kuwanon G against Streptococcus mutans causing dental caries was determined to be 8.0 microg/ml . The bactericidal test showed that kuwanon G completely inactivated S . mutans at the concentration 20 microg/ml in 1 min . Kuwanon G also significantly inhibited the growth of other cariogenic bacteria such as Streptococcus sobrinus and Streptococcus sanguis, and Porpyromonas gingivalis causing periodontitis . Transmission electron microscopy (TEM) of kuwanon G treated cells demonstrated remarkable morphological damage of the cell wall and condensation of the cytoplasm .

Ann Trop Paediatr, 2003 Mar, 23(1), 15 - 23
High burden of invasive Streptococcus agalactiae disease in South African infants; Madhi SA et al.; The epidemiology of invasive Streptococcus agalactiae (GBS) disease was evaluated in South African children . Records of 208/220 children in whom GBS was isolated between January 1997 and December 1999 were reviewed . These included 63%, 31.7% and 5.3% children with early- (EOD, <7 days of age), late- (LOD, age 7-90 days) and childhood-onset disease (COD, age >90 days), respectively . The overall burden of EOD and LOD were 2.06 and 1/1000 live births, respectively . The overall mortality was 19.8% and 13.6% for infants with EOD and LOD, respectively . Risk factors for mortality in infants with EOD and LOD included septic shock (82.1% vs 1.9%), prematurity (35.2% vs 9.6%), low birthweight (29.2% vs 11.0%) and a leucocyte count <5000/mm(3) (43.5% vs 18.6%) . Eight (72.7%) of 11 children with COD had an immunosuppressive, predisposing cause for invasive bacterial disease . In infants with EOD and LOD, serotype III isolates caused 49.2% and 75.7% of disease, respectively, and, together with serotype Ia isolates, caused 78.9% and 100% of invasive disease, respectively . Invasive GBS disease is common in South African infants and current strategies aimed at reducing the burden of the disease should be reconsidered.

Clin Experiment Ophthalmol, 2003 Apr, 31(2), 125 - 8
Topical anaesthesia: a risk factor for post-cataract-extraction endophthalmitis?
Ellis MF.
PURPOSE: To investigate if the incidence of postoperative endophthalmitis in temporal clear corneal cataract surgery is influenced by the use of topical anaesthesia compared to retrobulbar anaesthesia . METHODS: A retrospective study was conducted of one surgeon's cataract surgery between October 1997 and October 2001 . RESULTS: Between October 1997 and May 2000, there were 633 cataract extractions performed with 219 patients operated under topical anaesthesia and 414 under retro-bulbar injection . The selection criteria were that surgically easier cases underwent topical anaesthesia . There were five patients who suffered postoperative endophthalmitis in their first week, of which four cases were under topical anaesthesia . This was shown to be borderline significance of P = 0.05 using the Fischer exact 2-tailed test . There was a complicated case, operated under retrobulbar anaesthesia, who had a low-grade endophthalmitis in the second postoperative week . The four topical cases and the case from the second week all grew Staphylococcus epidermidis . The retrobulbar case developing endophthalmitis in the first week grew alpha haemolytic Streptococcus . After May 2000, there was a change to performing all cataract surgery under retrobulbar anaesthesia and the next 453 cases had no incidence of endophthalmitis . CONCLUSION: Topical anaesthesia techniques in temporal clear corneal cataract extraction may be a factor in endophthalmitis.

Am J Orthop, 2003 Mar, 32(3), 148 - 50
Primary bacterial pyomyositis associated with septic arthritis caused by Streptococcus pyogenes: a case report; Lawrentschuk N et al.; Pyomyositis is relatively rare in temperate climates . This is the first report of a case of calf pyomyositis associated with septic arthritis of the knee . This case illustrates that pyomyositis should be included in the differential diagnosis of a swollen, tender calf in an emergency setting . The other notable feature of this case is that the infective organism was not the usual Staphylococcus aureus but rather the relatively rarely involved Streptococcus pyogenes.

N Engl J Med, 2003 Mar 20, 348(12), 1112 - 21
An outbreak of conjunctivitis due to atypical Streptococcus pneumoniae; Martin M et al.; BACKGROUND: In February 2002, clinicians at the Dartmouth College Health Service recognized an outbreak of conjunctivitis; cultures of conjunctival swabs implicated Streptococcus pneumoniae . An investigation was begun to determine the extent of the outbreak, confirm the cause, identify modes of transmission, and implement control measures . METHODS: Investigators reviewed the health service's data base for diagnoses of conjunctivitis . Viral and bacterial cultures were obtained from ill students . Bile-soluble isolates that were susceptible to ethylhydrocupreine (optochin) and therefore were presumed to be pneumococci underwent serotyping, capsular staining, pulsed-field gel electrophoresis, a DNA probe, and multilocus sequence typing . A cohort study of risk factors was conducted with the use of the Internet . Control measures included distribution of alcohol-based hand gel and messages about prevention . RESULTS: Among 5060 students, 698 (13.8 percent) received a diagnosis of conjunctivitis from January 1, 2002, through April 12, 2002, including 22 percent of first-year students . Presumed pneumococci were isolated from 43.3 percent of conjunctival swabs (110 of 254); viral cultures performed on 85 specimens were negative . DNA probes and multilocus sequence typing confirmed that the organisms were pneumococci, although the bacteria did not have the characteristic capsule . On pulsed-field gel electrophoresis, strains were found to be identical to pneumococci that caused outbreaks of conjunctivitis in other parts of the country in 1980 . Analysis of survey data from 1832 students indicated that close contact with a student with conjunctivitis, wearing contact lenses, membership on a sports team, and attending parties at or living in a fraternity or sorority house were associated with conjunctivitis . The rate of diagnosis of conjunctivitis declined after the implementation of control measures and after spring break . CONCLUSIONS: This large outbreak of conjunctivitis on a college campus was caused by an atypical, unencapsulated strain of S . pneumoniae that was identical to strains that had caused outbreaks two decades earlier .

Biochem Biophys Res Commun, 2003 Mar 21, 302(4), 722 - 7
HrcA is a negative regulator of the dnaK and groESL operons of Streptococcus pyogenes; Woodbury R et al.; The genome of Streptococcus pyogenes, an important human pathogen, encodes homologs of the principal bacterial heat shock proteins DnaK and GroES, -EL, as well as HrcA, a negative regulator of dnaK and groESL expression in other Gram-positive bacteria . Using nuclease protection assays to measure dnaK/groESL mRNA abundance and a "non-polar" insertion to disrupt hrcA, we demonstrate that heat shock triggers a 4- to 8-fold increase in dnaK and groESL-specific mRNAs within 5 min of the temperature shift and that HrcA is a negative regulator of S . pyogenes dnaK/groESL mRNA abundance in unstressed S . pyogenes . Although the loss of HrcA elevated dnaK and groESL mRNA levels under non-heat shock conditions, the relative abundance of these RNAs increased further in heat shocked S . pyogenes, suggesting an additional element contributing to their synthesis or stability.

J Bacteriol, 2003 Apr, 185(7), 2362 - 8
Genome organization and molecular analysis of the temperate bacteriophage MM1 of Streptococcus pneumoniae; Obregon V et al.; The genome of MM1 (40,248 bp), a temperate bacteriophage from the Spain(23F)-1 multiresistant epidemic clone of Streptococcus pneumoniae, is organized in 53 open reading frames (ORFs) and in at least five functional clusters . Bioinformatic and N-terminal amino acid sequence analyses enabled the assignment of possible functions to 26 ORFs . Analyses comparing the MM1 genome with those of other bacteriophages revealed similarities, mainly with genomes of phages infecting gram-positive bacteria, which suggest recent exchange of genes between species colonizing the same habitat.

Pharmacol Res, 2003 Apr, 47(4), 355 - 62
Involvement of mitogen-activated protein kinases in Group B Streptococcus-induced macrophage apoptosis; Fettucciari K et al.; We previously demonstrated that Group B Streptococcus (GBS), a pathogen that causes serious neonatal infections, induces macrophage apoptosis by beta-hemolysin to avoid the host immune response . GBS-induced macrophage apoptosis is characterized by a calcium increase and is caspase-independent . This study reports the involvement of c-Jun NH(2)-terminal kinase (JNK), p38 and extracellular signal-regulated kinase (ERK), three members of mitogen-activated protein kinases (MAPKs) family, in GBS-induced macrophage apoptosis . Our data indicate that during induction of apoptosis live GBS stimulates a strong persistent activation of JNK and p38 with concomitant inhibition of ERK . The time courses of MAPKs activation strongly correlate with GBS-induced macrophage apoptosis and are macrophage:GBS ratio-dependent . In fact, when GBS does not cause macrophage apoptosis, e.g . low macrophage:GBS ratio or non hemolytic GBS (gGBS), it induces a transient activation of JNK, p38, and ERK MAPKs . These latter results indicate that sustained and persistent activation of JNK and p38 and inhibition of ERK are involved in the GBS-induced macrophage apoptotic process and suggest that the time course and balance of MAPKs activation are critical for different macrophage responses to GBS (apoptosis versus antimicrobicidal activity) . This study indicates a correlation between MAPKs activation and GBS-induced macrophage apoptosis . However, since neither ERK nor p38 inhibitors had an effect on GBS-induced apoptosis, their role in the complex signal network leading to GBS-induced macrophage apoptosis remains to be defined.

FEMS Microbiol Lett, 2003 Mar 14, 220(1), 113 - 9
Identification and characterization of four proteases produced by Streptococcus suis; Jobin MC et al.; Streptococcus suis is an important worldwide swine pathogen . In this study, we investigated the production of proteases by S . suis serotype 2 . Proteases were identified and characterized using chromogenic and fluorogenic assays and zymography . An Arg-aminopeptidase with a molecular mass of 55 kDa was found to be both cell-associated and extracellular . Cell-associated chymotrypsin-like and caseinase activities, belonging to the serine- and metalloprotease classes respectively, were also detected . Lastly, a dipeptidyl peptidase IV (DPP IV) with a molecular mass of 70 kDa was detected in both whole cells and culture supernatants of S . suis serotype 2 . Arg-aminopeptidase, caseinase and DPP IV activities were detected in all strains of S . suis serotype 2 tested whereas the chymotrypsin-like activity was only detected in European virulent strains of serotype 2 . The optimum pH for all four proteases was between 6 and 8, and the optimum temperature ranged from 25 to 42 degrees C . This is the first report on the production of proteases by S . suis . Further investigations will determine the possible contribution of these proteases in the pathogenicity of S . suis serotype 2.

Proc Natl Acad Sci U S A, 2003 Apr 1, 100(7), 4215 - 20 Epub 2003 Mar 17.
Antibody-enhanced pneumococcal adherence requires IgA1 protease; Weiser JN et al.; IgA, the major class of Ig in secretions, classically functions by interfering with microbial attachment to host tissues . Many mucosal pathogens, including Streptococcus pneumoniae, express an IgA1 protease that may circumvent the protective effects of this Ig subclass . Because these proteases are specific for human IgA1, we generated human mAbs to the major surface antigen of the pneumococcus, its capsular polysaccharide, and tested their effect in a colonization model of bacterial adherence to respiratory epithelial cells in culture . Rather than inhibiting adherence, type-specific IgA1 markedly enhanced bacterial attachment to host cells, but only when cleaved by IgA1 protease . Neither antibodies of protease-insensitive subclasses (IgA2 and IgG) nor those directed against heterologous capsules had such activity . The adherence-promoting properties of cleaved antibodies correlated with the cationic characteristics of their variable segments, suggesting that bound Fab fragments may neutralize the inhibitory effect of negatively charged capsules on adhesive interaction with host cells . Coating of pneumococci with anticapsular polysaccharide antibody unmasked the bacterial phosphorylcholine ligand, allowing for increased adherence mediated by binding to the platelet activating factor receptor on epithelial cells . In addition, our findings provide evidence for a novel function of bacterial IgA1 proteases . These enzymes may enable pathogens to subvert the antigen specificity of the humoral immune response to facilitate adhesive interactions and persistence on the mucosal surface.

Zhonghua Kou Qiang Yi Xue Za Zhi, 2002 Nov, 37(6), 456 - 8
{Construction and cellular expression of GTF-PAc fusion anti-caries DNA vaccine}; Jia R et al.; OBJECTIVE: To construct a fusion anti-caries DNA vaccine pGLUA-P carrying GLU fragment from gtfB gene of Streptococcus mutans GS-5 and A-P fragment including the A region and P region of PAc protein from a DNA anti-caries vaccine pCIA-P, and to investigate its expression in prokaryotic and eukaryotic cells . METHODS: The sequence of GLU fragment in pGLU plasmid was testified by DNA sequencing . The fusion anti-caries DNA vaccine was constructed by ligating A-P fragment from pCIA-P to pGLU . The expression of GLUA-P fusion protein in E . coli BL21 (DE3) was induced by IPTG and checked by SDS-PAGE electrophoresis . pGLUA-P was transfected in vitro to cultured rat primary muscle cells by cation liposome Dosper, and immunohistochemical method was used to test the expression of GLUA-P fusion protein in cells . RESULTS: GLU sequence was identical with relative sequence of GTF-I (GS-5 strain) in Gene Bank . Recombinant eukaryotic expression plasmid pGLUA-P was confirmed to have both GLU and A-P fragment . After pGLUA-P was transferred into E . coli (DE3), it could express a new 115 000 protein by the induce of IPTG . Specific brown products could be found in the cytoplasm of cultured rat primary muscle cells transfected by pGLUA-P . CONCLUSIONS: Fusion anti-caries DNA vaccine pGLUA-P is successfully constructed and confirmed by sequencing and enzymes digestion . Fusion GLUA-P protein can be correctly expressed in prokaryotic and eukaryotic cells.

Zhonghua Kou Qiang Yi Xue Za Zhi, 2002 Nov, 37(6), 452 - 5
{Intranasal immunization against dental caries with plasmid DNA encoding pac gene of Streptococcus mutans in gnotobiotic rats}; Guo J et al.; OBJECTIVES: To assess the efficacy of plasmid DNA encoding pac gene of Streptococcus mutans (S . mutans) intranasally immunized in gnotobiotic rats and to compare the effect of two different delivery systems . METHODS: Sprague Dawley rats, infected with S . mutans at 20 days of age, were intranasally immunized with plasmid pCIA-P (group A), Dosper-DNA complex (group B), Bupivacaine-DNA complex (group C) . Control rats were either immunized with plasmid pCI (group D), distilled water (group E) or immunized intramuscularly (group F) . All the rats were boosted 2 weeks later . ELISA determined the antibodies against the vaccines . Keyes caries score was used to evaluate the anti- caries effectiveness of the vaccines at the terminal study . RESULTS: As for the antibody reactions, there were significantly (P < 0.01) differences between rats immunized with DNA vaccine and non-immunized rats . And rats in group B and C had the significantly (P < 0.01) higher level of specific salivary anti-PAc IgA antibodies and rats (group B, C, F) had the significantly (P < 0.01) higher specific serum anti-PAc IgG responses to DNA vaccine . Keyes scores of rats (group B and C) were significantly (P < 0.01) lower than others . CONCLUSIONS: Intranasal immunization with plasmid pCIA-P encoding pac gene successfully reduces the caries and appears to be a promising approach against dental caries . Cationic liposome Dosper and local anesthetic bupivacaine could enhance the efficacy of DNA vaccine.

Orthop Nurs, 2003 Jan-Feb, 22(1), 4 - 8
Streptococcal fasciitis with toxic shock syndrome in the pediatric patient; Jackson MA et al.; Necrotizing fasciitis (NF) is a distinctive soft tissue infection usually caused by Group A beta-hemolytic streptococcus, often seen in association with varicella in the previously healthy child . Its fulminant course is associated with great morbidity and high case-fatality rates, especially when it occurs in conjunction with streptococcal toxic shock syndrome . It differs from simple cellulitis in clinical presentation, appearance on examination, and need for urgent surgical intervention . The patient is irritable and complains of severe pain in the involved site, which is usually the extremity . On examination, exquisite pain on palpation of the involved site is confirmed, which is out of proportion to the cutaneous findings . Shock, multiorgran failure, and death will ensue if the diagnosis is not promptly recognized . The five keys to management include fluid management, aggressive debridement of necrotic tissues, anticipation and management of multisystem organ failure, appropriate parenteral antimicrobial therapy using penicillin and clindamycin, and use of intravenous immunoglobulin (IVIG).

Gen Dent, 2002 Jul-Aug, 50(4), 340 - 3
In vitro testing of xylitol as an anticariogenic agent; Sahni PS et al.; A number of studies involving xylitol chewing gum have demonstrated that xylitol is both noncariogenic and anticariogenic . The ability of xylitol to act as an anticariogenic agent most likely is due to its ability to be transported into caries-causing oral bacteria and inhibiting fermentation either by depleting the cell of high-energy phosphate or by poisoning the glycolytic system . In vitro tests were conducted to determine the concentration of xylitol required to inhibit the growth of three strains of oral streptococcus (S . mutans, S . salivarius, and S . sanguis) . All three strains were inhibited significantly at xylitol concentrations of 12.5% and higher; however, only S . mutans was inhibited significantly at a xylitol concentration of 1.56%.

Vaccine, 2003 Apr 2, 21(15), 1562 - 71
Pneumococcal conjugate vaccines: proceedings from an interactive symposium at the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; Pelton SI et al.; Globally, Streptococcus pneumoniae is a leading cause of invasive and noninvasive disease in infants and young children . The emergence of antibiotic-resistant strains has increased interest in prevention through immunization . Currently, the only available conjugate pneumococcal vaccine is a seven-valent formulation, PNCRM7 . This paper presents excerpts from a symposium that provided an update of ongoing surveillance data and clinical trials evaluating pneumococcal conjugate vaccines . The topics addressed included: (1) PNCRM7 postmarketing safety data; (2) the impact of PNCRM7 in premature infants; (3) the direct and indirect effect of pneumococcal conjugate vaccines on colonization; (4) the effect of pneumococcal conjugate vaccines on replacement disease and the rate of resistance among replacement serotypes; (5) the current recommendations for the use of PNCRM7; and (6) the potential impact of conjugate vaccines in Europe and the Asia-Pacific region.

Equine Vet J, 2003 Mar, 35(2), 146 - 51
Brain abscesses as a metastatic manifestation of strangles: symptomatology and the use of magnetic resonance imaging as a diagnostic aid; Spoormakers TJ et al.; REASONS FOR PERFORMING STUDY: The occurrence of unexpectedly high numbers of horses with neurological signs during two outbreaks of strangles required prompt in-depth researching of these cases, including the exploration of magnetic resonance imaging (MRI) as a possible diagnostic technique . OBJECTIVES: To describe the case series and assess the usefulness of MRI as an imaging modality for cases suspected of space-occupying lesions in the cerebral cavity . METHODS: Four cases suspected of suffering from cerebral damage due to Streptococcus equi subsp . equi infection were examined clinically, pathologically, bacteriologically, by clinical chemistry (3 cases) and MRI (2 cases) . In one case, MRI findings were compared to images acquired using computer tomography (CT) . RESULTS: In all cases, cerebral abscesses positive for Streptococcus equi subsp . equi were found, which explained the clinical signs . Although the lesions could be visualised with CT, MRI images were superior in representing the exact anatomic reality of the soft tissue lesions . CONCLUSIONS: The diagnosis of bastard strangles characterised by metastatic brain abscesses was confirmed . MRI appeared to be an excellent tool for the imaging of cerebral lesions in the horse . POTENTIAL CLINICAL RELEVANCE: The high incidence of neurological complications could not be explained but possibly indicated a change in virulence of certain strains of Streptococcus equi subsp . equi . MRI images were very detailed, permitting visualisation of much smaller lesions than demonstrated in this study and this could allow prompt clinical intervention in less advanced cases with a better prognosis . Further, MRI could assist in the surgical treatment of brain abscesses, as has been described earlier for CT.

Ann Ig, 2002 Nov-Dec, 14(6 Suppl 7), 7 - 16
{Epidemiology of meningitis, pneumonia and acute otitis due to Streptococcus pneumoniae in pediatric in Italy}; Esposito S et al.; Streptococcus pneumoniae is one of the most important bacterial pathogens in pediatrics, both from a quantitative and from a qualitative point of view . It can cause severe diseases such as occult bacteremia, sepsis, meningitis and it is also involved in the determination of a relevant part of very common illnesses such as pneumonia, acute otitis media and rhinosinusitis . However, most of the data regarding the epidemiology of pneumococcal infections in pediatrics have been collected in the U.S.A . and in other industrialized Countries different from Italy . In Italy only studies concerning meningitis and the carrier state of pneumococcus are at the moment available . They indicate that also in Italy S . pneumoniae seems to play a significant role in the determination of several pediatric diseases and that quite similar are the group of serotypes mainly involved in the determination of both invasive and not invasive diseases.

Am J Orthod Dentofacial Orthop, 2003 Mar, 123(3), 345 - 8
Effect of sustained-release chlorhexidine varnish on Streptococcus mutans and Actinomyces viscosus in orthodontic patients; Beyth N et al.; This study evaluated the effect of sustained-release chlorhexidine varnish on orthodontic patients . Ten children, ages 10 to 16 years, participated . Bacterial levels of Streptococcus mutans and Actinomyces viscosus and total counts were evaluated in sputum samples . These counts were evaluated at 4 stages: before orthodontic treatment, at least 2 weeks after bonding of the brackets, 1 week after application of chlorhexidine varnish, and 3 weeks after application of chlorhexidine varnish . Increases in bacterial levels of S mutans and in the total bacterial count were detected after the brackets were bonded . One week after the sustained-release chlorhexidine varnish was applied, a significant decrease of total bacterial levels and S mutans was observed . This decrease persisted for 3 weeks after the first application . No significant change in A viscosus levels occurred during that period . The results provide additional evidence that sustained-release chlorhexidine varnish decreases S mutans levels in orthodontic patients with fixed appliances and therefore might be useful in preventing caries lesions.

Am J Physiol Heart Circ Physiol, 2003 Jul, 285(1), H47 - 58 Epub 2003 Mar 13.
Cardiac effects of burn injury complicated by aspiration pneumonia-induced sepsis; White J et al.; Early fluid resuscitation, antimicrobials, early excision, and grafting have improved survival in the early postburn period; however, a significant incidence of pneumonia-related sepsis occurs after burn injury, often progressing to multiple organ failure . Recent studies have suggested that this initial injury (burn injury) primes the subject, producing an exaggerated response to a second insult, such as pneumonia-related sepsis . We developed an experimental animal model that included a third-degree burn over 40% of the total body surface area, followed by sepsis (intratracheal administration of Streptococcus pneumoniae, 4 x 106 colony-forming unit), which was produced either 48 or 72 h after burn injury in adult male rats . Hearts harvested after either burn alone, sepsis alone, or burn plus sepsis were used to assess either contractile function (Langendorff) or cardiomyocyte secretion of tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, and IL-10 (ELISA) . Experimental groups included the following: 1) . sham (sham burn and no sepsis); 2) . burn injury alone studied either 24, 48, or 72 h postburn; 3) . pneumonia-related sepsis in the absence of burn injury; and 4) . pneumonia-induced sepsis studied either 48 or 72 h after an initial burn injury . Burn injury alone (24 h) or sepsis alone produced myocardial contractile defects and increases in pro- and anti-inflammatory cytokine secretion by cardiomyocytes . Sepsis that occurred 48 h postburn exacerbated the cardiac contractile defects seen with either burn alone or sepsis alone . Sepsis that occurred 72 h postburn produced contractile defects resembling those seen in either burn alone or sepsis alone . In conclusion, our data suggest that burn injury primes the subject such that a second insult early in the postburn period produces significantly greater cardiac abnormalities than those seen with either burn alone or sepsis alone.

Biochim Biophys Acta, 2003 Mar 21, 1646(1-2), 173 - 83
Identification and characterization of a new ligand-binding site in FnbB, a fibronectin-binding adhesin from Streptococcus dysgalactiae; Visai L et al.; Streptococcus dysgalactiae S2, a bovine mastitis isolate, expresses the fibronectin (Fn)-binding adhesin FnbB . Here, we describe a new fibronectin-binding domain called UFnBD, located 100 amino acid N-terminal to the primary repetitive Fn-binding domain (FnBRD-B) of FnbB . UFnBD interacted with N-terminal region of Fn (N29) and this binding was mostly mediated by type I module pair 2-3 of N29 fragment, whereas FnBRD-B mainly bound to type I module pair 4-5 . Furthermore, UFnBD inhibited adherence of S . dysgalactiae to Fn but at lower level as compared to FnBRD-B . UFnBD exclusively shared antigenic properties with the Fn-binding unit Du of FnbpA from Staphylococcus aureus but not with ligand-binding domains or motifs of other adhesins, while Fn-induced determinants of FnBRD-B and other adhesins appeared to be conformationally related . Consistent with this, a monoclonal antibody 7E11 generated from a mouse immunized with FnbB, and that recognized UFnBD did not cross-react with FnBRD-B . The epitope for 7E11 was mapped to 40 amino acid long segment within UFnBD and interaction between the antibody and the epitope was specifically induced by Fn or N29 . A similar antibody epitope was observed in Streptococcus pyogenes strains suggesting the presence of an adhesin bearing epitope related to FnbB.

Med Clin (Barc), 2003 Mar 8, 120(8), 292 - 4
{Pneumococcal pneumonia in hospitalized patients . Therapeutic implications of resistances to penicillin and erythromycin}; Sanz Herrero F et al.; BACKGROUND AND OBJECTIVE: Streptococcus pneumoniae is the main etiological agent of community-acquired pneumonia . The aim of this work was to ascertain the resistance profiles of pneumococcus to penicillin and erythromycin and to analyse whether such profiles lead to different disease developments . PATIENTS AND METHOD: A retrospective analysis was carried out in 75 cases of pneumococcal pneumonia corresponding to hospitalized patients . Comorbidity factors were evaluated including their influence on the appearance of resistance . RESULTS: 67 patients (89.3%) presented comorbidity factors . 49.3% isolates displayed some type of resistance: 38.6% to penicillin, 36% to erythromycin and 13.3% to cefotaxime . No relationship was observed between the severity of the pneumonia and antibiotic resistance . Complications and mortality were not influenced by the susceptibility of pneumococcus to antibiotics . CONCLUSION: The increase in the resistance to antibiotics, especially erythromycin, makes betalactams the best choice for the treatment of pneumococcal pneumonia.

Microbiol Immunol, 2003, 47(1), 17 - 25
Transposon-induced norfloxacin-sensitive mutants of Bacteroides thetaiotaomicron; Ueda O et al.; To elucidate the mechanism of norfloxacin (a fluoroquinolone) resistance of Bacteroides thetaiotaomicron, a member of the B . fragilis group, we isolated transposon-induced mutants sensitive to this agent using Tn4351 . Four norfloxacin-sensitive mutants showed reduced levels of resistance, at least, to ethidium bromide . Cloning and sequencing of three chromosomal fragments adjacent to Tn4351 from the mutants revealed that two partial open reading frames (orfs) were disrupted by a transposon . Amino acid sequences of partial orf products had strong homologies to those of Escherichia coli RecB and B . ovatus transketolase . Two mutants carried a recB homolog inserted by Tn4351 together with R751 (cointegration) and by itself (simple transposition) at the amino- and carboxyl-terminal portions, respectively . Since mutations in recB produce E . coli cells sensitive to DNA-damaging treatments by quinolones, it is concluded that decreases of the minimum inhibitory concentrations (MICs) of the agents for B . thetaiotaomicron resulted from disruption of the recB homolog . Another mutant carried a transketolase gene inserted by Tn4351 . There is no reasonable explanation why disruption of the transketolase gene caused a decrease of the MIC of norfloxacin for this organism, although Streptococcus pneumoniae RecP related to DNA recombination was reported to be transketolase.

Intern Med, 2003 Feb, 42(2), 208 - 10
Multibacterial sepsis in an alcohol abuser with hepatic cirrhosis; Matsukawa Y et al.; An alcohol abuser with hepatitis C developed multibacterial sepsis . His mean 100% alcohol intake reached 400 ml/day . In January 2001, he suddenly experienced fever (39 degrees C) with no other symptoms . One week later, he was admitted to our hospital and was subsequently diagnosed with sepsis associated with four species of bacteria (Streptococcus constellatus, Fusobacterium mortiferum, Bacteroides thetaiotaomicron, and non-spore-forming anaerobic gram-positive bacillus) . A drip infusion of imipenem/cilastatin was administrated, resulting in a successful therapeutic outcome . No underlying disorder was found except for gastric ulcers and hepatic cirrhosis . Damaged gastric mucosa was assumed to be the possible cause and route for the bacterial invasion.

J Am Dent Assoc, 2003 Feb, 134(2), 200 - 7
The diagnosis and management of recurrent aphthous stomatitis: a consensus approach; Scully C et al.; BACKGROUND: Recurrent aphthous stomatitis, or RAS, is a common oral disorder of uncertain etiopathogenesis for which symptomatic therapy only is available . This article reviews the current data on the etiopathogenesis, diagnosis and management of RAS in a primary care setting . METHODS: The authors reviewed publications on Medline from 1995 through 2000, the period since the last major reviews were published . RESULTS: RAS may have an immunogenetic background owing to cross-reactivity with Streptococcus sanguis or heat shock protein . Predisposing factors seen in a minority include haematinic (iron, folate or vitamin B12) deficiency, stress, food allergies and HIV infection . While topical corticosteroids remain the mainstay for therapy, a number of other immunomodulatory modalities now are available . CONCLUSIONS: There is still no conclusive evidence relevant to the etiopathogenesis of RAS, and therefore therapy can attempt only to suppress symptoms rather than to address the basic issues of susceptibility and prevention . CLINICAL IMPLICATIONS: In the majority of patients, symptomatic relief of RAS can be achieved with topical corticosteroids alone, with other immunomodulatory topical agents or by combination therapy.

J Virol, 2003 Apr, 77(7), 4104 - 12
Influenza A virus-infected hosts boost an invasive type of Streptococcus pyogenes infection in mice; Okamoto S et al.; The apparent worldwide resurgence of invasive Streptococcus pyogenes infection in the last two decades remains unexplained . At present, animal models in which toxic shock-like syndrome or necrotizing fasciitis is induced after S . pyogenes infection are not well developed . We demonstrate here that infection with a nonlethal dose of influenza A virus 2 days before intranasal infection with a nonlethal dose of S . pyogenes strains led to a death rate of more than 90% in mice, 10% of which showed necrotizing fasciitis . Infection of lung alveolar epithelial cells by the influenza A virus resulted in viral hemagglutinin expression on the cell surface and promoted internalization of S . pyogenes . However, treatment with monoclonal antibodies to hemagglutinin markedly decreased this internalization . Our results indicate that prior infection with influenza A virus induces a lethal synergism, resulting in the induction of invasive S . pyogenes infection in mice.

J Comp Pathol, 2003 Feb-Apr, 128(2-3), 156 - 64
Early pathogenesis and inflammatory response in experimental bovine mastitis due to Streptococcus uberis; Pedersen LH et al.; A generally similar clinical response was observed in six lactating Holstein-Friesian cows after intramammary inoculation with approximately 10(7) colony-forming units of Streptococcus uberis . Increased concentrations of serum amyloid A (SAA) were measured in both milk and serum taken 6 and 11h after inoculation, respectively . In contrast, increased concentrations of haptoglobin were detected after 10h of infection, in milk only . In the blood, tumour necrosis factor-alpha (TFN-alpha) was detected (0.503 ng/ml) in only one animal, at the time of euthanasia (10h after infection) . Interferon-gamma (IFN-gamma), like haptoglobin, was not detected in blood . Parallel to the development of inflammation and influx of inflammatory cells into the udder tissue, a marked decrease in the number of monocytes and neutrophils in blood was observed . Bacteria were found both intracellularly (macrophages and neutrophils) and within the lumen of ducts and alveoli . Lesions developed progressively in an ascending manner and became widespread throughout the mammary gland in less than 8h . The parallel development of inflammation and increased concentrations of SAA and haptoglobin in milk points to these acute phase proteins as potential diagnostic markers for the early detection of S . uberis -associated mastitis.

Int J Pediatr Otorhinolaryngol, 2003 Mar, 67(3), 277 - 81
Acute mastoiditis in children: Pseudomonas aeruginosa as a leading pathogen; Butbul-Aviel Y et al.; OBJECTIVE: Acute mastoiditis is a serious bacterial infection of the temporal bone and is the most common complication of otitis media . The goal of this study is to assess the clinical features, pathogens, management, and outcome of acute mastoiditis in children in northern Israel . METHODS: A systematic review of medical records of all children who were admitted with acute mastoiditis from January 1990 through December 2000 . RESULTS: Fifty-seven children were included . Median was age: 36 months . In 26 patients (45.6%) mastoiditis complicated the first episode of acute otitis media (AOM) . Twenty-five children (44%) received antibiotic treatment prior to admission . Frequent symptoms included mastoid area erythema in 54 children (94.7%), proptosis of the auricle in 52 children (91.2%) and fever in 43 children (75.4%) . Middle ear, and subperiostal culture yielded growth of pathogen in 30 children (75%), two cultures yielded more then one pathogen . The most frequent pathogens were: Pseudomonas aeruginosa in 10 children (25%), Streptococcus pneumoniae in eight children (20%), Group A streptococcus in six children (15%) . The highest incidence of Streptococcus pneumoniae was found in children who did not suffer from AOM before admission (35 vs . 5%) . Fifty-two (91.2%) children were cured with antibiotic treatment alone . Seventeen children underwent computed tomography (CT) of the mastoid . Mastoid bone destruction was demonstrated in six children and subperiostal abscess in eight . Mastoidectomy was performed in five children . CONCLUSIONS: The diagnosis of acute mastoiditis can be made on clinical basis alone requiring CT only when complications are suspected . Half of the children admitted with acute mastoiditis had no previous history of recurrent AOM . In those children S . pneumoniae was the leading pathogen while P . aeruginosa was more prevalent in children with recurrent AOM . Most of the children recovered with medical therapy alone, without surgical intervention.

Acta Paediatr Taiwan, 2002 Nov-Dec, 43(6), 326 - 9
Group B streptococcus infection in infancy: 21-year experience; Liao CH et al.; In this hospital-based review, clinical presentations associated with Group B streptococcus (GBS) infections in children occurring between January 1980 and March 2000 were analyzed . Among the 25 infants with invasive group B streptococcal infections, 9 (36%) were early onset diseases (EOD), 12 (48%) were late onset diseases (LOD), and 4 (16%) occurred beyond the third month of life . Eight of the nine (89%) EOD cases manifested during the first day of life and three (33%) were premature births . Common presentations in GBS infection were fever (75%), poor activity (25%), respiratory distress (25%), lethargy (20%), and irritability (20%) . Seizure occurred in 31% of infants with meningitis . Pneumonia (66%) and case-fatality rate (33.3%) were significantly higher in EOD than in LOD . Meningitis was the major manifestation (77%) of LOD and had severe sequelae in 40% of cases . Eight strains were assayed for antibiotic sensitivity and they were all susceptible to penicillin, ampicillin, cefotaxime, and vancomycin . The susceptibilities to erythromycin and clindamycin were 62% and 75%, respectively . Most of the strains from blood or cerebrospinal fluid were type III.

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