Streptococci

An Pediatr (Barc), 2003 Dec, 59(6), 565 - 70
{Cost benefit analysis of body surface cultures at a neonatal unit}; Marugan Isabel V et al.; INTRODUCTION: Infection continues to be a cause of concern in neonatal units . The high cost of the body surface cultures used to study infection and their limited utility is controversial . MATERIAL AND METHODS: The medical records of newborns admitted for suspected infection in 1999 were retrospectively reviewed . Request criteria, cost, and the clinical utility of body surface cultures were analyzed . RESULTS: In 1999, body surface cultures were requested in 204 newborns admitted to hospital (70 % of all admitted newborns) . Of these, six were diagnosed with bacteremia (6.23/1000; 95 % CI: 5.9-6.5) . The most frequently isolated microorganisms were Escherichia coli and Streptococcus agalactiae . The total cost of body surface cultures was 6,510.95 euros (1,083,331 pesetas) . In 25 % of cases the results of cultures influenced clinical decision making . The cost necessary to obtain clinical repercussion in a patient was 191.50 euros (31,863 pesetas) . Requesting two body surface cultures only (otic and umbilical) halved the cost without diminishing their clinical utility . CONCLUSIONS: A considerable percentage of newborns admitted to hospital present suspected infection requiring microbiological studies . Although the cost of body surface cultures is high, the results of these cultures influence diagnostic and therapeutic decisions in a quarter of patients . We do not believe that eliminating the use of these cultures would be beneficial . However, their cost can be reduced by carefully selecting request criteria and by limiting cultures to two samples (otic and umbilical).

Eur J Immunol, 2003 Dec, 33(12), 3322 - 30
Critical role of Valpha14+ natural killer T cells in the innate phase of host protection against Streptococcus pneumoniae infection; Kawakami K et al.; The present study was designed to elucidate the role of Valpha14(+) NKT cells in the host defense against pulmonary infection with Streptococcus pneumoniae using Jalpha281 gene-disrupted mice (Jalpha281KO mice) that lacked this lymphocyte subset . In these mice, pneumococcal infection was severely exacerbated, as shown by the shorter survival time and marked increase of live bacteria in the lung compared to wild-type (WT) mice . The proportion of Valpha14(+) NKT cells, detected by an alpha-galactosylceramide (alpha-GalCer)-loaded CD1d tetramer, increased in thelung after S . pneumoniae infection . This increase was significantly reduced in mice with a genetic disruption of monocyte chemotactic protein (MCP)-1, which was produced in the early phaseof infection in WT mice . In the lungs of Jalpha281KO mice, the number of neutrophils was significantly lower at 12 h than that in WT mice . In support of this finding, macrophage inflammatory protein (MIP)-2 and TNF-alpha synthesis in infected lungs was significantly reduced at 3 h and at both 3 and 6 h, respectively, in Jalpha281KO mice, compared to WT mice . In addition, treatment of mice with alpha-GalCer significantly improved the outcome of this infection . Our results demonstrated MCP-1-dependent recruitment of Valpha14(+) NKT cells and their critical role in early host protection against S . pneumoniae by promoting the trafficking of neutrophils to the site of infection.

Alcohol Clin Exp Res, 2003 Nov, 27(11), 1838 - 45
Alcohol-induced suppression of lung chemokine production and the host defense response to Streptococcus pneumoniae; Boe DM et al.; BACKGROUND: Acute alcohol intoxication impairs neutrophil migration in response to intrapulmonary infection with Streptococcus pneumoniae, the most common bacterial cause of pneumonia . Many of the same host defense functions that are impaired in the alcohol-intoxicated host are mechanistically associated with chemokines, a group of proinflammatory molecules that enhance neutrophil adhesion and direct neutrophil migration to sites of inflammation . The purpose of this study was to determine whether alcohol-induced chemokine suppression is responsible for impaired neutrophil recruitment into the lung during infection of the alcohol-intoxicated host . METHODS: S . pneumoniae was administered (107 colony-forming units) intratracheally 30 min after intraperitoneal injection of 20% alcohol (5.5 g/kg) or saline . Four hours after bacterial challenge, bronchoalveolar lavage fluid (BALF) was collected, and the ability of BALF to induce neutrophil chemotaxis and adhesion molecule expression was measured by using chemotactic and flow cytometric assays . In another experiment, intratracheal challenge was performed by using recombinant macrophage inflammatory protein-2 (MIP-2), and BALF neutrophils were measured . RESULTS: BALF MIP-2 and cytokine-induced neutrophil chemoattractant were decreased by alcohol, and BALF from alcohol-intoxicated animals had decreased chemotactic activity for neutrophils, as well as a decreased ability to up-regulate neutrophil adhesion molecule expression, compared with controls . This decreased chemotactic activity was significantly increased in the alcohol group by repletion of chemokines to control levels . Alcohol also suppressed neutrophil recruitment after intrapulmonary challenge with MIP-2, suggesting that mechanisms other than chemokine suppression contribute to the alcohol-induced effect . CONCLUSIONS: At least two mechanisms, suppressed chemokine production and impaired neutrophil adhesion molecule expression, likely work in concert in the alcohol-intoxicated host to impair neutrophil adhesion and migration into the lung during pneumococcal infection . These alterations in neutrophil function likely increase the susceptibility of alcohol-consuming hosts to pneumonia.

Microb Drug Resist, 2003, 9 Suppl 1, S61 - 8
Inferring the potential success of pneumococcal vaccination in Italy: serotypes and antibiotic resistance of Streptococcus pneumoniae isolates from invasive diseases; Pantosti A et al.; To evaluate the potential impact of antipneumococcal vaccination in Italy, Streptococcus pneumoniae isolates from invasive disease were collected from 65 laboratories in the years 1997-2000 . Of the 503 isolates examined, 15% were from children <5 years and 34% from adults > or = 65 years . The most frequent serogroups were, in ranking order, 14, 19, 6, and 23 . Overall, 93.8% of the isolates belonged to serogroups enclosed in the 23-valent polysaccharide vaccine . Among children isolates, serotypes 14, 6B, and 23F comprised 60% of the isolates; overall, 72% of the isolates belonged to serotypes included in the heptavalent conjugate vaccine . Penicillin nonsusceptible isolates (10%) belonged to a limited number of serogroups, being more common in serogroups 19 and 9 and in the nonvaccine serogroups 24 and 35 . Erythromycin-resistant isolates (29%) belonged to several serogroups, more frequently to serogroups 14, 6, and 19 . Both vaccines are potentially able to prevent the majority of resistant infections in the respective age groups in Italy.

Microb Drug Resist, 2003, 9 Suppl 1, S53 - 9
Experimental study of clinafloxacin alone and in combination in the treatment of ciprofloxacin-susceptible and -resistant pneumococcal meningitis; Domenech A et al.; The increasing incidence of ciprofloxacin resistance in Streptococcus pneumoniae may limit the efficacy of the new quinolones in difficult-to-treat infections such as meningitis . The aim of the present study was to determine the efficacy of clinafloxacin alone and in combination with teicoplanin and rifampin in the therapy of ciprofloxacin-susceptible and ciprofloxacin-resistant pneumococcal meningitis in rabbits . When used against a penicillin-resistant ciprofloxacin-susceptible strain (Clinafloxacin MIC 0.12 microg/ml), clinafloxacin at a dose of 20 mg/kg per day b.i.d . decreased bacterial concentration by -5.10 log cfu/ml at 24 hr . Combinations did not improve activity . The same clinafloxacin schedule against a penicillin- and ciprofloxacin-resistant strain (Clinafloxacin MIC 0.5 microg/ml) was totally ineffective . Our data suggest that a moderate decrease in quinolone susceptibility, as indicated by the detection of any degree of ciprofloxacin resistance, may render these antibiotics unsuitable for the management of pneumococcal meningitis.

Microb Drug Resist, 2003, 9 Suppl 1, S35 - 8
Phenotypic and genetic characterization of resistance against macrolides and lincosamides in Streptococcus gallolyticus strains isolated from pigeons and humans; Kimpe A et al.; The macrolide and lincosamide (ML) resistance phenotype of 65 pigeon and 30 human Streptococcus gallolyticus strains was determined by the disk diffusion method . Constitutive resistance against the tested antibiotics was seen in 13 human and 28 pigeon strains . Simultaneous screening for the presence of erm(B) and mef(A) genes using PCR revealed that the erm(B) gene was present in 40 out of these 41 phenotypically resistant S . gallolyticus strains while the mef(A) gene was detected in only one resistant and one susceptible human-derived strain . The erm(B) genes of 10 human and 10 pigeon S . gallolyticus strains were sequenced and compared . Four human and seven pigeon strains possessed exactly the same sequence for the erm(B) gene . The sequence of the erm(B) gene of the remaining strains differed in one to five nucleotides . These findings could indicate a possible exchange of resistance genes between human and pigeon strains.

Lett Appl Microbiol, 2003, 37(5), 370 - 3
Detection of Streptococcus anginosus from saliva by real-time polymerase chain reaction; Kumagai K et al.; AIMS: The purpose of the present investigation was to assess the salivary levels of Streptococcus anginosus in periodontitis patients . METHODS AND RESULTS: The salivary levels of Strep . anginosus were assessed using real-time polymerase chain reaction (PCR) . Streptococcus anginosus was detected in 28 of 37 (75.6%) of periodontitis patients and in three of the 20 (15%) healthy subjects . The mean values for bleeding on probing and probing depth in positive patients were statistically higher than those in negative patients . A significant decrease in Strep . anginosus levels was observed after periodontal treatment . CONCLUSIONS: Although the levels of Strep . anginosus are extremely low, they may reflect the status of periodontal health . SIGNIFICANCE AND IMPACT OF THE STUDY: Real-time PCR is a useful method for obtaining the relative quantities of Strep . anginosus from saliva samples and for monitoring the effect of therapy.

Paediatr Drugs, 2003, 5 Suppl 1, 35 - 46
Acute bacterial skin infections in pediatric medicine: current issues in presentation and treatment; Hedrick J; Bacterial skin and skin structure infections commonly encountered in children include impetigo, folliculitis, furunculosis, carbuncles, wound infections, abscesses, cellulitis, erysipelas, scarlet fever, acute paronychia, and staphylococcal scalded skin syndrome . If diagnosed early and treated appropriately, these infections are almost always curable, but some have the potential to cause serious complications such as septicemia, nephritis, carditis and arthritis if diagnosis is delayed and/or treatment is inadequate . During the initial evaluation, it is important to determine whether the infection is superficial or deep, and whether it is localized or spreading . Prompt treatment is essential if the infection appears to be spreading, as the sequelae can be life threatening . Once the proper diagnosis is made, the next important step is selecting the most appropriate therapy . In children presenting with mild or moderately severe bacterial skin and skin structure infections and not requiring inpatient management or urgent operative debridement, prompt provision of oral antimicrobial therapy avoids the risk of worsening infection or hospitalization . Empiric antimicrobial therapy should be directed at the most likely pathogens, (e.g . Staphylococcus aureus or Streptococcus pyogenes), although some infections (e.g . subcutaneous abscesses and cellulitis following animal or human bites) may have a polymicrobial origin . In choosing the appropriate antimicrobial therapy, one must take into account the resistance profile of the target pathogen, the agent's antibacterial profile and intrinsic activity against the target pathogen, and its pharmacokinetic properties (including absorption, elimination, and extent of tissue penetration) . Other factors to consider include tolerability of the drug, convenience of the dosing regimen, and acceptability and palatability of the oral formulation administered . Any treatment plan for bacterial skin and skin structure infections should aim to minimize the emergence of resistant organisms so that the risk of their dissemination to others in the community is reduced . Oral antimicrobial agents currently available that may be considered include: beta-lactamase-stable penicillins (e.g . cloxacillin, dicloxacillin, and amoxicillin-clavulanate potassium), the macrolides (e.g . erythromycin, clarithromycin, and azithromycin), and the cephalosporins . Cephalosporins are now the most commonly used class, particularly because of increasing resistance among strains of S . pyogenes to erythromycin (and by implication, the other macrolides) . The second- and third-generation cephalosporins have many advantages, with their extended spectra of antimicrobial activity, favorable pharmacokinetic and tolerability profiles, and convenient dosage schedules . The third-generation agent, cefdinir, has good activity against a broad range of likely pathogens, including staphylococci, a twice-daily administration schedule, a favorable efficacy and tolerability profile, is well accepted by young children when administered as an oral suspension, and may be an attractive alternative in the pediatric setting.

Paediatr Drugs, 2003, 5 Suppl 1, 13 - 23
Acute streptococcal pharyngitis in pediatric medicine: current issues in diagnosis and management; Shulman ST; Group A beta-hemolytic streptococcus (GABHS) is the most common bacterial cause of acute pharyngitis . Although children infected with GABHS will recover clinically without antibiotics, treatment is recommended in order to prevent acute rheumatic fever and probably suppurative complications, hasten resolution of clinical signs and symptoms, and prevent transmission to close contacts . Streptococcal pharyngitis usually cannot be reliably distinguished from other etiologies on the basis of epidemiologic or physical findings, and therefore a throat culture or a rapid antigen detection test is generally necessary to confirm the diagnosis . All isolates of GABHS are sensitive to penicillins and cephalosporins, whereas resistance to macrolides has been identified in some geographic regions . The recommended first-line therapy for streptococcal pharyngitis is a 10-day course of penicillin V, usually given 2 or 3 times per day . A number of alternatives to penicillin V are available, including other penicillins, macrolides, and cephalosporins . As a class, the cephalosporins are noteworthy because they may provide somewhat higher bacteriologic eradication rates than penicillin V . Many cephalosporins can be administered twice daily, but they also must be given for 10 days . Two third-generation cephalosporins, cefdinir and cefpodoxime proxetil, are approved for use in a more convenient 5-day dosing schedule, thus possibly increasing the likelihood of adherence to the full course of therapy . Palatability is also an important consideration when prescribing antibiotics to children . In a series of studies, children preferred the pleasant strawberry-cream taste of cefdinir to that of amoxicillin/clavulanate, cefprozil, and azithromycin . Cefdinir may offer an alternative to penicillin V for children with streptococcal pharyngitis, particularly when compliance is a clinical concern.

Presse Med, 2003 Sep 6, 32(28 Suppl), S24 - 6
{Following the serotypes of pneumococcal strains isolated in asplenic subjects}; Varon E; EPIDEMIOLOGY: There have been relatively few studies concerning the epidemiology of Streptococcus pneumoniae infections in asplenic subjects, and even fewer concerning pneumococcal carriage . A small number of studies provide data on serotype frequency, or simply on serogroups . The frequency of pneumococcal carriers among sickle-cell anemia children varies from 6% to 27% depending on the series and the type of sampling used (rhinopharyngeal or oropharyngeal) . IMPORTANCE OF SURVEILLANCE: It is particularly important to carefully follow the evolution of the serotypes and sensitivities of pneumococci isolated from carriers in order to assess the selective pressure of the antibiotic prophylaxis and to determine the impact of anti-pneumococcal vaccination in this population, as in the general population.

Infect Dis Obstet Gynecol, 2003, 11(2), 117 - 22
Second-trimester pregnancy loss at an urban hospital; Heller DS et al.; OBJECTIVES: Second-trimester spontaneous pregnancy losses are less common than first-trimester losses, and are often associated with ascending infection and/or acute chorioamnionitis . A Medline search revealed only two large studies published in the recent literature, reporting incidences of chorioamnionitis of 39.3% and 58.2%, respectively . These studies did not address the use of histopathology for the identification of organisms . Since ascending infection is likely to be a significant cause of second-trimester loss in the inner-city population at the University Hospital in Newark, New Jersey, we sought to evaluate the usefulness of stains for microorganisms, which are rarely utilized on these specimens . METHODS: Retrospective review of the medical records and pathologic material for cases of spontaneous abortions seen at the University Hospital in Newark between January 1999 and March 2001 was undertaken . Stains for microorganisms were performed on archival placental tissue for cases with histologic acute chorioamnionitis . RESULTS: A total of 67 cases were available for review, of which 38 cases (56.7%) showed histologic acute chorioamnionitis, similar to the rates in one previous study, but significantly higher than those in the other (p = 0.01) . Of 25 cases with histological chorioamnionitis for which appropriate fetal material was available, 13 cases (52%) showed polymorphonuclear leukocytes (PMNs) in the fetal lungs, one case (4%) showed PMNs in the fetal stomach, and seven cases (28%) showed PMNs in both the lung and the stomach . Of the 38 cases with chorioamnionitis, Gram stains showed Gram-positive cocci in six cases, two of which were culture positive for group B streptococcus . Warthin-Starry stains showed filamentous organisms consistent with Fusobacterium sp . in the placenta in three cases . CONCLUSIONS: Acute chorioamnionitis is associated with second-trimester pregnancy loss at this inner-city hospital, and may be related to the high incidence of risk factors in this population . A small proportion of cases can be further characterized by the inclusion of Gram and Warthin-Starry stains in the evaluation . Selection of cases with histologic acute chorioamnionitis for further study with special stains may provide additional information on the causative organism.

Int J Clin Pract, 2003 Oct, 57(8), 735 - 6
A case of septicaemia, meningitis and pneumonia caused by Streptococcus bovis type II; Namiduru M et al.; We present a case of septicaemia, pneumonia and meningitis due to Streptococcus bovis type-II in a patient who had undergone a total hip prosthesis under general anaesthesia three weeks earlier . This organism is an uncommon human pathogen that sometimes causes bacteraemia and endocarditis and is usually connected with colon pathology and dental procedures . In the reported case, there were no risk factors for S . bovis infection except for the hip operation . S . bovis type II sensitive to penicillin was isolated from all blood and pleural fluid cultures . The patient recovered and was discharged from hospital two weeks after presentation.

Nat Biotechnol, 2003 Dec, 21(12), 1480 - 5 Epub 2003 Nov 16.
An engineered multidomain bactericidal peptide as a model for targeted antibiotics against specific bacteria; Qiu XQ et al.; We constructed a peptide consisting of a staphylococcal AgrD1 pheromone fused to the channel-forming domain of colicin Ia and named it pheromonicin . This fusion peptide had bactericidal effects against methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA, respectively), but not against Staphylococcus epidermidis or Streptococcus pneumoniae . Growth rates, vital staining and colony forming unit (CFU) counts showed that pheromonicin did not merely suppress growth but killed S . aureus cells . The specificity of pheromonicin was shown by the absence of bactericidal effects against an accessory gene regulator (agr) locus knockout of S . aureus, and a dose-dependent inhibition of the bactericidal effects of pheromonicin by competition with corresponding free AgrD pheromone . In vivo, all pheromonicin-treated mice survived administration of MRSA that was lethal to controls . No toxicity was detectable in human liver or renal cells in culture, or in livers, kidneys or spleens of pheromonicin-treated mice . The results suggest that these types of chimeric peptides may be of value as antibiotics against specific bacterial infections.

J Infect Dis, 2003 Nov 15, 188(10), 1587 - 92 Epub 2003 Nov 10.
Array of M protein gene subtypes in 1064 recent invasive group A streptococcus isolates recovered from the active bacterial core surveillance; Li Z et al.; Using sequence analysis to detect variation within the hypervariable M protein N terminus, we found 41 emm types encompassing 81 subtypes, among 1064 consecutive invasive group A streptococcus isolates from a recent multistate, population-based surveillance . Seventeen of the 30 emm types represented by multiple isolates displayed multiple subtypes . Most subtypes differed from reference strain emm sequences as a result of single base substitutions or other alterations likely to be stably inherited . The Centers for Disease Control and Prevention database (available at: currently contains 225 distinct emm types encompassing 450 subtypes . Although this subtyping scheme increases specificity, limited variation within individual types favors introduction of M protein type-specific vaccines.

Mol Microbiol, 2003 Nov, 50(4), 1103 - 10
From nose to lung: the regulation behind Streptococcus pneumoniae virulence factors; Hava DL et al.; Streptococcus pneumoniae probably possesses a redundant set of factors required for colonization of the nasopharynx and invasive disease, because of its strict relationship with its human host and relatively small genome size (approximately 2.1 Mb) . Nevertheless, transcriptional regulation of genes encoding factors required for in vivo growth is predicted to be important on two fronts: in the transition from carriage to invasive disease and within different microniches of the nasopharynx . The importance of both serotype-specific and host tissue-specific virulence factors during infection and disease has been highlighted by the recent identification of novel virulence factors in this organism coupled with the release of complete genome sequences from two strains . These studies add to the foundation of knowledge of classical S . pneumoniae virulence factors such as polysaccharide capsule and pneumolysin, which have well-documented roles in pathogenesis.

Oral Microbiol Immunol, 2003 Dec, 18(6), 371 - 8
A rapid procedure to ascertain the antimicrobial efficacy of oral care formulations; Sreenivasan PK et al.; A rapid method examining the antimicrobial efficacy of oral care formulations with alamar blue, an oxidation-reduction dye with fluorescent end-points, is described . Significant correlations between increasing viable plate counts of the oral bacteria Actinomyces viscosus, Streptococcus sanguis, Streptococcus mutans and Actinobacillus actinomycetemcomitans and increased alamar fluorescence were noted . Metabolically active bacteria reduced alamar with the reduced dye found in the cell-free filtrate . Insignificant alamar reductions were noted in the absence of bacteria or by spent culture supernatants . The efficacy of mouthrinses with clinically proven antiplaque agents such as chlorhexidine or cetylpyridinium chloride were determined by alamar blue . In a model system with A . viscosus, triclosan dentifrices demonstrate a dose-dependent effect on bacteria . Human salivary bacteria demonstrate increasing alamar fluorescence with increasing plate counts . A clinical study examined the effects of rinsing with chlorhexidine or cetylpyridinium chloride mouthrinses in comparison with a placebo mouthrinse and water on salivary bacteria . Rinsing with chlorhexidine resulted in the least number of bacteria by alamar and plate count methods . In summary, the current study demonstrates the utility of alamar blue to examine the antimicrobial effects of oral care formulations in laboratory and clinical studies.

Scand J Infect Dis, 2003, 35(9), 683 - 9
Intravenous immunoglobulin adjunctive therapy in sepsis, with special emphasis on severe invasive group A streptococcal infections; Norrby-Teglund A et al.; Immunotherapy targeted against microbial toxins and host mediators has been studied in many preclinical investigations and clinical trials of sepsis during the past 20 y . Intravenous immunoglobulin, including both monoclonal and polyclonal antibodies, represents one such immunotherapeutic strategy . Mononclonal antibodies directed against endotoxin or tumour necrosis factor-alpha have been tested extensively in clinical trials, but have so far failed to reveal a significant effect on mortality rates . Several studies have assessed the efficacy of polyclonal intravenous immunoglobulin (IVIG) in sepsis, with varying results . Although there are no conclusive data available to date to support the use of IVIG therapy in all sepsis cases, there are strong indications that certain defined septic subgroups, such as streptococcal toxic shock syndrome caused by group A streptococcus, will benefit from its use . This review briefly summarizes the clinical trials on IVIG therapy in sepsis, and describes in more detail the mechanistic actions of IVIG and the clinical data that support the use of IVIG as adjunctive therapy in severe invasive group A streptococcal infections.

Scand J Infect Dis, 2003, 35(9), 647 - 52
Organ-specific models of Streptococcus pneumoniae disease; Orihuela CJ et al.; The variability of the course of infection by Streptococcus pneumoniae is well known but poorly understood . Most animal models of pneumonia, sepsis or meningitis have been forced to use site-specific bacterial inoculation to mimic localized human infection . This study examined the differences in the progression of disease-causing strains D39 (serotype 2), A66.1 (serotype 3) and TIGR4 (serotype 4) using isolates transformed with the Gram-positive lux transposon cassette, Tn4001 luxABCDE Km(r) . Expression of the lux operon results in bioluminescence, permitting the detection of the bacteria within a living animal while using a CCD camera . Mice infected intranasally with A66.1 developed only pneumonia, those challenged with D39 experienced high-grade sepsis, while TIGR4 infection resulted in low-grade pneumonia and bacteremia ultimately progressing to meningitis . Quantitative analysis of bacterial titers confirmed these patterns, which were consistent across different lineages of mice . Mice anesthetized with ketamine and xylazine developed more severe forms of the disease compared with isoflurane . These studies unambiguously characterize 3 distinct models of the natural course of pneumococcal infection . Mapping these models provides a framework for detailed molecular modeling of pneumococcal virulence determinants at specific stages of disease.

Scand J Infect Dis, 2003, 35(9), 632 - 41
Proinflammatory activity of cell-wall constituents from gram-positive bacteria; Moreillon P et al.; Innate immunity reacts to conserved bacterial molecules . The outermost lipopolysaccharide (LPS) of Gram-negative organisms is highly inflammatory . It activates responsive cells via specific CD14 and toll-like receptor-4 (TLR4) surface receptor and co-receptors . Gram-positive bacteria do not contain LPS, but carry surface teichoic acids, lipoteichoic acids and peptidoglycan instead . Among these, the thick peptidoglycan is the most conserved . It also triggers cytokine release via CD14, but uses the TLR2 co-receptor instead of TLR4 used by LPS . Moreover, whole peptidoglycan is 1000-fold less active than LPS in a weight-to-weight ratio . This suggests either that it is not important for inflammation, or that only part of it is reactive while the rest acts as ballast . Biochemical dissection of Staphylococcus aureus and Streptococcus pneumoniae cell walls indicates that the second assumption is correct . Long, soluble peptidoglycan chains (approximately 125 kDa) are poorly active . Hydrolysing these chains to their minimal unit (2 sugars and a stem peptide) completely abrogates inflammation . Enzymatic dissection of the pneumococcal wall generated a mixture of highly active fragments, constituted of trimeric stem peptides, and poorly active fragments, constituted of simple monomers and dimers or highly polymerized structures . Hence, the optimal constraint for activation might be 3 cross-linked stem peptides . The importance of structural constraint was demonstrated in additional studies . For example, replacing the first L-alanine in the stem peptide with a D-alanine totally abrogated inflammation in experimental meningitis . Likewise, modifying the D-alanine decorations of lipoteichoic acids with L-alanine, or deacylating them from their diacylglycerol lipid anchor also decreased the inflammatory response . Thus, although considered as a broad-spectrum pattern-recognizing system, innate immunity can detect very subtle differences in Gram-positive walls . This high specificity underlines the importance of using well-characterized microbial material in investigating the system.

J Bacteriol, 2003 Dec, 185(23), 6815 - 25
Factors contributing to hydrogen peroxide resistance in Streptococcus pneumoniae include pyruvate oxidase (SpxB) and avoidance of the toxic effects of the fenton reaction; Pericone CD et al.; Aerobic growth of Streptococcus pneumoniae results in production of amounts of hydrogen peroxide (H(2)O(2)) that may exceed 1 mM in the surrounding media . H(2)O(2) production by S . pneumoniae has been shown to kill or inhibit the growth of other respiratory tract flora, as well as to have cytotoxic effects on host cells and tissue . The mechanisms allowing S . pneumoniae, a catalase-deficient species, to survive endogenously generated concentrations of H(2)O(2) that are sufficient to kill other bacterial species is unknown . In the present study, pyruvate oxidase (SpxB), the enzyme responsible for endogenous H(2)O(2) production, was required for survival during exposure to high levels (20 mM) of exogenously added H(2)O(2) . Pretreatment with H(2)O(2) did not increase H(2)O(2) resistance in the mutant, suggesting that SpxB activity itself is required, rather than an H(2)O(2)-inducible pathway . SpxB mutants synthesized 85% less acetyl-phosphate, a potential source of ATP . During H(2)O(2) exposure, ATP levels decreased more rapidly in spxB mutants than in wild-type cells, suggesting that the increased killing of spxB mutants was due to more rapid ATP depletion . Together, these data support the hypothesis that S . pneumoniae SpxB contributes to an H(2)O(2)-resistant energy source that maintains viability during oxidative stress . Thus, SpxB is required for resistance to the toxic by-product of its own activity . Although H(2)O(2)-dependent hydroxyl radical production and the intracellular concentration of free iron were similar to that of Escherichia coli, killing by H(2)O(2) was unaffected by iron chelators, suggesting that S . pneumoniae has a novel mechanism to avoid the toxic effects of the Fenton reaction.

Clin Microbiol Infect, 2003 Oct, 9(10), 1038 - 44
Prospective evaluation of blood cultures in a Turkish university hospital: epidemiology, microbiology and patient outcome; Esel D et al.; The aims of this prospective study were to: (1) determine the rate of blood culture contamination; (2) describe and compare the epidemiologic, clinical and microbiological characteristics of hospital- and community-acquired bloodstream infections; and (3) determine the mortality resulting from bloodstream infections . The rate of true bacteremia was 12.1%, and 10.7% of cultures were contaminated . Of the 567 episodes of bloodstream infection, 73.4% were hospital-acquired, and 26.6% were community-acquired . The most commonly isolated microorganisms were staphylococci (44%, methicillin resistant 69.4%), enterococci (15%) and Escherichia coli (12.5%) in hospital-acquired episodes, and Brucella spp . (21.9%), E . coli (19.2%) and Staphylococcus aureus (14.6%, methicillin resistant 9.1%) in community-acquired episodes . While the overall mortality rate was 25.4%, death attributable to bloodstream infections was 16.6% in hospital-acquired episodes and 13.9% in community-acquired episodes . The highest mortality occurred in patients with bacteremia due to Pseudomonas aeruginosa (37.5%) in hospital-acquired episodes, and in patients with bacteremia due to Streptococcus pneumoniae (50%) in community-acquired episodes . Underlying diseases, severity of illness, presence of bladder catheter, previous use of antibiotics, tracheal intubation and adequacy of treatment were found to be significantly associated with death.

Clin Microbiol Infect, 2003 Oct, 9(10), 1031 - 4
Invasive properties of south Indian strains of Streptococcus pyogenes in a HEp-2 cell model; Gladstone P et al.; The objective of this study was to consider the invasive properties of Streptococcus pyogenes in human pharyngeal epithelial cells, and to correlate these with their clinical significance . Clinical isolates of S . pyogenes obtained from blood cultures over a period of 10 years, and throat and skin isolates from a community-based study, were used in this investigation . The S . pyogenes isolates were inoculated in HEp-2 cells and subsequently treated with antibiotics to kill the extracellular bacteria . The cells were then lyzed, and a colony count was carried out to check for invasion . The throat and skin isolates had 45.7%, 25.7% and 28.5% of low, intermediate and high invasion efficiencies, respectively, while 80%, 8.6% and 11.4% of the blood isolates had low, intermediate and high invasion efficiencies . We concluded that the throat and the skin isolates from superficial infections were more invasive than the blood isolates, which is an interesting and paradoxical feature.

Clin Microbiol Infect, 2003 Aug, 9(8), 869 - 72
Streptococcus equi subspecies equi (Lancefield group C) meningitis in a child; Elsayed S et al.; We present a case of Streptococcus equi subsp . equi meningitis in a young boy . This case represents the first report in the literature of meningitis caused by this organism, as far as we know.

Clin Microbiol Infect, 2003 Aug, 9(8), 832 - 8
Group B streptococcus colonization of Greek pregnant women and neonates: prevalence, risk factors and serotypes; Tsolia M et al.; OBJECTIVE: To evaluate the prevalence and risk factors of group B streptococcus (GBS) colonization among pregnant women and their neonates in Greece, and to examine the serotype distribution of the GBS strains isolated and their susceptibility to antibiotics . METHODS: A vaginal and a rectal swab were obtained from 1014 pregnant or parturient women followed at public and private hospitals in Athens and in a city of northern Greece . Cultures were also taken 24 h after birth from 428 neonates born to these women . RESULTS: The overall maternal and neonatal colonization rates were 6.6% and 2.4%, respectively . The vertical transmission rate was 22.5% . By logistic regression analysis, multiparity (>/=III) was associated with a lower colonization rate (odds ratio 4.4, 95% confidence interval 1.08-18.63) . In contrast with other studies, middle-class women followed privately were more frequently colonized (10%) than those followed at the public hospital (3.9%) (odds ratio 3.1, 95% confidence interval 1.83-5.42) . A higher number of prenatal visits was also associated with a higher colonization rate (change in true odds ratio when visits increased by one, 1.3; 95% confidence interval 1.14-1.60) . No association was found between colonization and maternal age, previous obstetric history, marital status, nationality, prematurity, Caesarean section, or infant birth weight . The most common serotypes were II (26.9%), III (22.4%), Ia (19%), Ib (12%), and V (9%) . A considerable proportion of the isolated strains was resistant to erythromycin (4.5%), clindamycin (6%), or both (6%) . CONCLUSION: The rate and risk factors of maternal and neonatal GBS colonization may vary in different communities . These rates, as well as the incidence of neonatal disease, need to be thoroughly evaluated in each country to allow the most appropriate preventive strategy to be selected.

Clin Microbiol Infect, 2003 Sep, 9(9), 966 - 9
Development of macrolide resistance by ribosomal protein L4 mutation in Streptococcus pyogenes during miocamycin treatment of an eight-year-old Greek child with tonsillopharyngitis; Bozdogan B et al.; Streptococcus pyogenes isolates with the same pulsed-field patterns were recovered from the throat cultures of a child with tonsillopharyngitis before and after treatment with miocamycin, a 16-membered macrolide . The initial isolate was macrolide-susceptible, but the isolates after the treatment were resistant to 14 and 15-membered macrolides and had two amino acid (65WR66) deletions in ribosomal protein L4.

Clin Microbiol Infect, 2003 Sep, 9(9), 944 - 8
Rhabdomyolysis as a result of Streptococcus pneumoniae: report of a case and review; Blanco JR et al.; We report the case of a patient who presented with RM associated with bacteremic pneumococcal pneumonia and review the literature on this condition.

Clin Microbiol Infect, 2003 Sep, 9(9), 924 - 9
A common clone of erythromycin-resistant Streptococcus pneumoniae in Greece and the UK; Fotopoulou N et al.; OBJECTIVE: To investigate the possible genetic relationship among erythromycin-resistant Streptococcus pneumoniae strains isolated in Greece and the UK . METHODS: During 1995-97, 140 S . pneumoniae strains were isolated from clinical specimens submitted to the microbiology departments of the two main children's hospital in Athens . All erythromycin-resistant strains were further studied with respect to the presence of genes encoding for the two major mechanisms of macrolide resistance, their serotypes, and pulsed-field gel electrophoresis (PFGE) types, in comparison to a previously characterized UK erythromycin-resistant clone . RESULTS: Eleven of the 140 isolates (7.9%) were resistant to erythromycin; nine of these were susceptible to penicillin . Serotyping allocated seven, three and one isolates to serotypes 14, 19F and serogroup 6, respectively . The mefA gene was detected in seven isolates (five serotype 14 and two serotype 19F), ermB in two (one serotype 19F and the serogroup 6 isolate), whilst in the remaining two isolates no resistance gene could be detected by polymerase chain reaction (PCR) . Pulsed-field gel electrophoresis of genomic DNA showed that five Greek serotype 14 isolates belonged to the same chromosomal type as the serotype 14 erythromycin-resistant UK clone . CONCLUSIONS: The present study showed that erythromycin resistance among the S . pneumoniae isolates was mostly owing to the efflux mechanism and suggested a possible clonal spread of serotype 14 erythromycin-resistant S . pneumoniae strains between Greece and the UK.

APMIS, 2003 Oct, 111(10), 945 - 50
Serologically indicated pneumococcal pneumonia in children: a population-based study in primary care settings; Heiskanen-Kosma T et al.; The aim of the study was to assess age-specific incidences of community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae and diagnosed serologically in a child population . The study was population-based, and prospective, and performed in primary health care settings . During a surveillance period of 12 months from 1981-1982, all pneumonia cases in a defined child population (57% urban residents) were registered prospectively . In total, 201 CAP cases were diagnosed (mean age 5.6 years; 57% boys; 58% urban residents) . S . pneumoniae etiology was studied by antibody and immune complex (IC) assays to C-polysacchride (C-PS), type-specific capsular polysaccharides (CPS), and to pneumolysin (Ply), in acute and convalescent sera . Serologic evidence of S . pneumoniae etiology was indicated in 57(28%) cases, 35(61%) being mixed infections with other microbes . The distribution of pneumococcal cases was 44%, 30% and 26% in the three 5-year age groups, respectively . There were 33 (58%) males and 34 (60%) urban residents . In total, 26 cases were identified by antibody assays and 35 cases by IC assays, 26/35 being positive in acute sera . Responses to C-PS, CPS and Ply, when antibody and IC results are combined, were found equally often in 23-25 cases . The total annual incidence of pediatric S . pneumoniae CAP was 6.4/1000/year . S . pneumoniae etiology was found in 28% of the children and was similar at all ages . The incidence of pneumococcal CAP was assessed for the first time, being high (19/1000/year) in 0- to 4-year-old urban boys and rather stable (5-9/1000/year) in all other groups by age, sex and residence.

Aliment Pharmacol Ther, 2003 Nov 15, 18(10), 949 - 62
Review article: oral ulceration--aetiopathogenesis, clinical diagnosis and management in the gastrointestinal clinic; Field EA et al.; Oral ulceration is a common complaint of patients attending out-patient clinics . The aim of this review is to provide the gastroenterologist with a differential diagnosis of oral ulceration, and a practical guide for the management of recurrent aphthous stomatitis, including topical and systemic therapy . The association of recurrent aphthous stomatitis with Behcet's disease and other systemic disorders, including coeliac disease, is discussed . Recent evidence concerning the immunopathogenesis of Behcet's disease is reviewed, including renewed interest in the role of Streptococcus sanguis and possible infectious triggering of an inappropriate immunoinflammatory response, resulting in tissue damage . The efficacy and limitations of conventional treatment for this mutisystem disorder are outlined together with the potential role of novel biological agents, such as anti-tumour necrosis factor-alpha therapy . Oral ulceration, as a manifestation of inflammatory bowel disease and a complication of drug therapy, is described . Guidance is given concerning indications for referral of patients with oral ulceration to an oral physician/surgeon for further investigations, including biopsy if appropriate.

Clin Infect Dis, 2003 Dec 1, 37(11), 1534 - 40 Epub 2003 Nov 06.
Decreased serum opsonic activity against Streptococcus pneumoniae in human immunodeficiency virus-infected Ugandan adults; Takahashi H et al.; Type-specific immunoglobulin G (IgG) to pneumococcal capsular polysaccharide (CPS) and opsonic activity against Streptococcus pneumoniae were evaluated in serum samples from 36 Ugandan adults with community-acquired pneumonia and 58 asymptomatic Ugandan adults with or without human immunodeficiency virus type 1 (HIV-1) infection . The levels of serum IgG to CPS were significantly higher in HIV-1-infected subjects than in HIV-uninfected subjects . Serum samples from HIV-1-infected subjects that had lower IgG titers demonstrated higher opsonic activity against type 3 (titers of 7) and type 9 (titers of 7-11) pneumococcal strains . Plasma HIV-1 load also correlated inversely with serum opsonic activity against these strains, and peripheral blood CD4+ lymphocyte numbers also tended to correlate with serum opsonic activity in asymptomatic HIV-1-infected adults . Our findings suggest that the opsonic activity of type-specific IgG is impaired in the serum of HIV-1-infected African adults, which may expose them to a serious risk of invasive pneumococcal infections.

Clin Infect Dis, 2003 Dec 1, 37(11), 1481 - 9 Epub 2003 Nov 07.
Clinical presentation and bacteriologic analysis of infected human bites in patients presenting to emergency departments; Talan DA et al.; Previous studies of infected human bites have been limited by small numbers of patients and suboptimal microbiologic methodology . We conducted a multicenter prospective study of 50 patients with infected human bites . Seventy percent of the patients and assailants were young adult men . Fifty-six percent of injuries were clenched-fist injuries and 44% were occlusional bites . Most injuries were to the hands . Fifty-four percent of patients were hospitalized . The median number of isolates per wound culture was 4 (3 aerobes and 1 anaerobe); aerobes and anaerobes were isolated from 54% of wounds, aerobes alone were isolated from 44%, and anaerobes alone were isolated from 2% . Isolates included Streptococcus anginosus (52%), Staphylococcus aureus (30%), Eikenella corrodens (30%), Fusobacterium nucleatum (32%), and Prevotella melaninogenica (22%) . Candida species were found in 8% . Fusobacterium, Peptostreptococcus, and Candida species were isolated more frequently from occlusional bites than from clenched-fist injuries . Many strains of Prevotella and S . aureus were beta-lactamase producers . Amoxicillin-clavulanic acid and moxifloxacin demonstrated excellent in vitro activity against common isolates.

J Med Microbiol, 2003 Dec, 52(Pt 12), 1047 - 58
Using cpsA-cpsB sequence polymorphisms and serotype-/group-specific PCR to predict 51 Streptococcus pneumoniae capsular serotypes; Kong F et al.; Streptococcus pneumoniae polysaccharide and protein-conjugate vaccines are available against the most commonly isolated pneumococcal serotypes . Ongoing surveillance of invasive pneumococcal disease is needed in order to monitor changes in distribution of serotypes . Based on previously published sequences of capsular polysaccharide synthesis (cps) gene clusters of 16 pneumococcal serotypes, a molecular capsular typing (MCT) system has been developed, based on a combination of partial cpsA-cpsB sequencing and serotype- or serogroup-specific PCR, targeting the genes wzy and wzx (except for serotype 3) . In this study, 151 S . pneumoniae isolates of known serotype (representing 51 serotypes) and 276 recent clinical isolates were used to develop MCT and compare it with conventional serotyping (CS) (total 427 isolates) . On the basis of 376 heterogeneity sites in the cpsA-cpsB region, 89 sequence types (ST) were identified, of which 76 corresponded to a single serotype and 11 contained two serotypes . The correct serotypes in two of the latter (10A-23F-g and 23F-23A) were identified using serotype 23F-specific PCR . Limited CS was required for 92 (22 %) isolates to distinguish between the two serotypes in the nine other mixed ST (6A-6B-g, 6A-6B-q, 15B-22F, 33F-33A, 17F-35B, 18B-18C, 13-20, 25F-38, 31-42) . MCT is a specific, objective and practical method that can predict the serotype of most S . pneumoniae isolates; it will facilitate epidemiological studies . Further study of the relationship between MCT and CS is needed in order to improve our understanding of serotype differentiation and to improve MCT methods further.

J Antimicrob Chemother, 2003 Dec, 52(6), 967 - 73 Epub 2003 Nov 12.
Phage lytic enzymes as therapy for antibiotic-resistant Streptococcus pneumoniae infection in a murine sepsis model; Jado I et al.; OBJECTIVES: Phage-coded lysins, i.e . murein hydrolases, are enzymes that destroy the cell wall of bacteria . A rapid killing of Streptococcus pneumoniae in the nasopharynx of mice has been described recently using a phage-coded murein hydrolase (enzybiotic) . The in vivo effects of a dose-ranging treatment, using either of the phage-coded lytic enzymes Cpl-1 lysozyme or the Pal amidase, have been investigated here in a murine sepsis model . METHODS: Purified Pal amidase and/or Cpl-1 lysozyme were used alone or in combination . These enzymes were injected intraperitoneally at different times after challenge with 5 x 10(7) cfu of a type 6B, antibiotic-resistant S . pneumoniae clinical isolate . RESULTS: Animals challenged with 5 x 10(7) cfu of this strain alone died within 72 h, whereas a single intraperitoneal injection of Cpl-1 or Pal (200 microg; 1100 U) administered 1 h after the bacterial challenge was sufficient to effectively protect the mice, according to unpaired t-test (P<0.0001) . Bacteraemia in unprotected mice reached colony counts >10(7) cfu/mL, whereas the mean colony count in lysin-protected animals was <10(6) cfu/mL over time and ultimately became undetectable . Interestingly, a synergic effect in vivo was observed with the combined use of 2.5 microg each of Cpl-1 and Pal . CONCLUSIONS: Our findings suggest strongly that phage lysins protect animals from bacteraemia and death . Moreover, the simultaneous attack of the pneumococcal peptidoglycan by a lysozyme and an amidase leads to a remarkable effect through enhanced destruction of the bacterial cell wall . The benefits of therapy with enzybiotics against pneumococcus reported here might warrant the examination of alternative strategies for the treatment of diseases caused by clinically relevant pathogens.

Ann Clin Microbiol Antimicrob . 2003 Nov 7;2(1):9.
Recurrent pneumococcal meningitis in a splenectomised HIV-infected patient; Morand PC et al.; BACKGROUND: Streptococcus pneumoniae is a major cause of human disease, especially in pre-school children and elderly people, as well as in special risk groups such as asplenic, antibody deficient patients, or presenting disruption of natural barriers . The occurrence of pneumococcal disease has increased with the onset of the HIV epidemic and the emergence of drug-resistance . CASE PRESENTATION: We report the case of an HIV-1-infected patient who experienced three episodes of recurrent pneumococcal meningitis over a 4-year period, despite chemoprophylaxis and capsular vaccination . CONCLUSIONS: Efficacy of anti-pneumococcal chemoprophylaxis and vaccination in HIV-infected patients are discussed in the light of this particular case.

Curr Opin Allergy Clin Immunol, 2003 Dec, 3(6), 451 - 9
Primary immunodeficiencies associated with pneumococcal disease; Picard C et al.; PURPOSE OF REVIEW: Streptococcus pneumoniae may cause disease in patients with a variety of primary immunodeficiencies . However, no previous review has dealt with the issue of which primary immunodeficiencies predispose affected individuals to pneumococcal disease . We thus reviewed the medical literature on cases of S . pneumoniae infection in patients with primary immunodeficiency diseases, with a particular emphasis on invasive pneumococcal disease . RECENT FINDINGS: Primary immunodeficiency diseases comprise over 100 conditions, each associated with a variety of infections . Patients at high risk for pneumococcal disease include most if not all B-cell defects (whether due to an intrinsic B-cell anomaly or an impaired T-cell help), deficiencies of early components of the classical pathway of complement and C3 deficiency, congenital asplenia, anhidrotic ectodermal dysplasia with immunodeficiency (caused by impaired NF-kappaB activation), and interleukin-1 receptor associated kinase-4 deficiency . Patients with other complement deficiencies (alternative and third pathway) and hyperimmunoglobulin E syndrome show a lower risk, whereas patients with other known primary immunodeficiencies, such as phagocytic disorders, do not appear to be particularly vulnerable to S . pneumoniae . SUMMARY: Antibody- and complement-mediated opsonization, splenic macrophages and interleukin-1 receptor associated kinase-4- and nuclear factor kappaB-mediated immune responses are crucial for protective immunity to S . pneumoniae . This information is useful, not only in increasing our understanding of human immunity to S . pneumoniae, but also in the diagnostic investigation of patients with pneumococcal disease.

J Biol Chem, 2004 Jan 30, 279(5), 3375 - 81 Epub 2003 Nov 11.
Improving protein pharmacokinetics by genetic fusion to simple amino acid sequences; Alvarez P et al.; The role of primary amino acid sequences in protein pharmacokinetics, an issue of relevance in both basic knowledge and biotechnology, was addressed here using as a starting point two repetitive antigens from the hemoflagellate Trypanosoma cruzi that are known to stabilize their associated proteins in the bloodstream . A major drawback to their pharmacological application is that these repetitive sequences are highly immunogenic, being therefore the deletion of this characteristic desirable . Based on sequence homology and epitope mapping analyses, an artificial repetitive sequence (PSTAD) was engineered . This motif was tested by genetic fusion to the C terminus of both the trypanosomal trans-sialidase and the rat tyrosine aminotransferase and found to produce a 4.5-6-fold increase in the half-life of the associated proteins in blood while displaying significantly lower immunogenicity . Residues involved in the stabilizing properties of the novel peptide were mapped by a site-directed mutagenesis approach, allowing us to successfully identify another two motifs . Searching databases for sequences displaying some homology, embedded in proline frameworks and associated to shed virulence factors from unrelated microorganisms, resulted in the identification of four other protein extensions . Remarkably, three of them (from Streptococcus pneumoniae, Actinomyces viscosus, and Escherichia coli) revealed similar pharmacokinetic features, suggesting therefore an analogous evolutionarily acquired mechanism to ensure the biodistribution of their corresponding proteins . Our findings indicate that the insertion of defined motifs into a proline-rich framework constitutes a suitable alternative to construct a chimeric protein with extended half-life in blood.

Arch Dis Child, 2003 Nov, 88(11), 1009 - 14
Empyema thoracis: a 10-year comparative review of hospitalised children from south Asia; Baranwal AK et al.; AIMS: To study the clinical and microbial profile of childhood empyema in South Asia and to identify the changes over the past three decades . METHODS: A total of 265 children (aged 1 month to 12 years) with empyema admitted to the Advanced Pediatric Center, PGIMER, Chandigarh, India in 1989-98, were reviewed retrospectively . RESULTS AND CONCLUSIONS: One third of children were under 5 . Culture positivity had decreased significantly (48% v 75%) over the years . Staphylococcus aureus continues to be the commonest (77%) aetiological agent; clustering was seen during hot and humid months (46%) . Culture positive Streptococcus pneumoniae cases also decreased (9% v 27%); all were seen during the winter and spring season . Gram negative rods grew in more patients (11% v 7%) . Community acquired methicillin resistant S aureus (MRSA) was isolated in three patients . Most children (93%) were treated with parenteral cloxacillin and an aminoglycoside . Tube drainage (TD) was used in 92% of fibropurulent cases, and was successful in 79% . Of 48 patients with failed TD, 12 needed decortication; limited thoracotomy was sufficient in the remaining 36 . Surgery was mainly required by children with persistent pleural sepsis after 10 days of TD . Delaying surgery until 14 days had a significantly higher potential of requiring decortication . Early change to oral antibiotics (after 1-2 weeks of parenteral therapy) reduced the hospital stay significantly (17+7 v 23+7 days) without compromising long term outcome . Twenty two patients presenting late in the chronic stage underwent decortication at admission.

J Ethnopharmacol, 2003 Dec, 89(2-3), 301 - 3
Antibacterial activity of Leontopodium alpinum (Edelweiss); Dobner MJ et al.; Extracts and individual constituents of Leontopodium alpinum Cass . (Asteraceae) were tested for their antimicrobial activity in two different assays . Extracts were screened in agar diffusion assays, whereas the minimum inhibitory concentrations (MIC) of single compounds were determined by the microbroth dilution method according to NCCLS criteria . Significant antimicrobial activities were found against various strains of Enterococcus faecium, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes strains . These results support the ethnomedicinal use of Leontopodium alpinum for the treatment of respiratory and abdominal disorders.

Eur J Pediatr, 2004 Jan, 163(1), 19 - 21 Epub 2003 Nov 11.
Group A streptococcal meningitis as a complication of an infected capillary haemangioma; Rezvani M et al.; We report a case of group A streptococcal meningitis in an infant resulting from an infected capillary haemangioma . The child suffered significant morbidity including cerebral infarction, epilepsy, and developmental delay . Treatment of infected capillary haemangiomas remains controversial and inconsistent . CONCLUSION: Our experience of this infant, resulting in profound neurological morbidity suggests that group A Streptococcus can be a virulent organism in the young child and that capillary haemangiomas must be treated aggressively at the first sign of infection.

Proc Natl Acad Sci U S A, 2003 Nov 25, 100(24), 14363 - 7 Epub 2003 Nov 10.
Pneumococcal carriage results in ganglioside-mediated olfactory tissue infection; van Ginkel FW et al.; Streptococcus pneumoniae cause considerable morbidity and mortality, with persistent neurological sequelae, particularly in young children and the elderly . It is widely assumed that carriage occurs through direct mucosal colonization from the environment whereas meningitis results from invasion from the blood . However, the results of published studies can be interpreted that pneumococci may enter the brain directly from the nasal cavity by axonal transport through olfactory nerves . This hypothesis is based on findings that (i) teichoic acid of the pneumococcal cell wall interact with gangliosides (GLS), (ii) the interaction of GLS with cholera toxin leads to axonal transport through the olfactory nerves into the brain, and (iii) viruses enter the brain through axonal transport into olfactory nerves . After nasal inoculation, we observe high numbers of pneumococci in nasal washes and the olfactory nerves and epithelium . Significant numbers of pneumococci also infected the olfactory bulbs, brain, and the trigeminal ganglia . The absence of bacteremia in this model makes it unlikely that the bacteria entered the brain from the blood stream . Recovery of colony-forming units from the brain, lungs, olfactory nerves, and epithelium and nasal washes was inhibited by incubating pneumococci with GLS before nasal inoculation . These findings, confirmed by PCR and immunohistochemistry, support a GLS-mediated process of infection and are consistent with pneumococci reaching the brain through retrograde axonal transport.

Minerva Pediatr, 2003 Oct, 55(5), 439 - 45
{Nasopharyngeal colonization of Streptococcus pneumoniae in healthy children: percentage of carriers, serotypes distribution and antibiotic resistance}; Schettini F Jr et al.; AIM: The nasopharyngeal carriage of Streptococcus pneumoniae is an important risk factor for pneumococcal diseases . Data regarding prevalence and serotype distribution of this pathogen are lacking in our population . METHODS: Experimental design: longitudinal observational cohort study . Setting: healthy children aged 1-7 years attending day-care centers and schools of a district of a Southern Italy city . Measures: the nasopharyngeal colonization rate of Streptococcus pneumoniae as well as its antibiotic susceptibility was determined . RESULTS: Of 317 nasopharyngeal cultures obtained, 18.29% of the cultures were positive for Streptococcus pneumoniae; 60.34% of the isolates were serotypes 19A, 19F, 14, 6B, or 23F; 8.62% of the strains were intermediately resistant to penicillin . Erythromycin-resistance was observed in 65.51% of the micro-organisms isolated and particularly serotypes 19, 14, and 6 were more erythromycin-resistant than organisms of other serotypes . Co-trimoxazole resistance was detected in 17.24% of the strains . All the strains resulted uniformly susceptible to cefotaxime and ceftriaxone . CONCLUSION: The high rate of nasopharyngeal carriage of Streptococcus pneumoniae, along with the resistance to antibiotics widely used in the community, suggests the importance of an epidemiological surveillance as well as the application of new vaccine strategies.

Clin Diagn Lab Immunol, 2003 Nov, 10(6), 1019 - 24
Multilaboratory evaluation of a viability assay for measurement of opsonophagocytic antibodies specific to the capsular polysaccharides of Streptococcus pneumoniae; Romero-Steiner S et al.; Opsonophagocytosis is a correlate of protection that measures the functional activity of vaccine-induced antibodies . A standardized opsonophagocytosis assay (OPA) should be used as part of the evaluation of current and future pneumococcal (Pnc) polysaccharide (Ps)-based vaccines . We enrolled five laboratories to evaluate a previously standardized viability OPA . Each laboratory was provided with a detailed OPA protocol, seven target Pnc strains (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F), two quality control sera and 12 paired sera (blinded) from adult donors who received one dose of the 23-valent Pnc Ps vaccine . Laboratories sent their results to the Centers for Disease Control and Prevention for analysis . Sera were tested in duplicate (single run), and the results were averaged to yield a single OPA titer (> or = 50% killing) for each serum sample . The percentage of sera within one or two dilutions of the calculated median OPA titer was determined for each laboratory and for each serotype . In general, laboratories were capable of detecting OPA titers within one or two dilutions of the median for at least 75 and 88%, respectively, of the sera tested . The level of agreement with the median OPA titers varied depending on the participating laboratory (overall agreement = 0.8 {99% confidence interval = 0.75 to 0.85}) . All OPA median titers reported for quality control sera were within one dilution of the expected titer . We conclude that this OPA can be done in multiple laboratories with a high degree of interlaboratory reproducibility.

Scand J Infect Dis, 2003, 35(10), 757 - 9
Different polymerase chain reaction-based analyses for culture-negative endocarditis caused by Streptococcus pneumoniae; Voldstedlund M et al.; Two cases of culture-negative infective endocarditis caused by Streptococcus pneumoniae are presented . Conventional bacteriological methods were compared with 2 different polymerase chain reaction (PCR)-based analyses: PCR amplification with primers specific for S . pneumoniae, and broad-range PCR followed by sequencing . PCR-based analyses can be a valuable supplement to traditional bacteriological analyses.

Immunogenetics, 2003 Dec, 55(9), 629 - 32 Epub 2003 Nov 06.
Alleles carried at positions -819 and -592 of the IL10 promoter affect transcription following stimulation of peripheral blood cells with Streptococcus pneumoniae; Temple SE et al.; IL-10 inhibits the production of many pro-inflammatory cytokines . Polymorphisms in the IL10 gene promoter at positions -1082G-->A, -819C-->T and -592C-->A occur as three haplotypes, ATA, GCC and ACC . These influence several infectious and inflammatory diseases including community-acquired pneumonia, where a role for IL-10 is suggested by fluctuations in plasma levels of the cytokine . However, the effects of the haplotypes on IL-10 production are unclear . We stimulated peripheral blood mononuclear cells (PBMC) from at least five individuals homozygous for each of the three haplotypes with lipopolysaccharide (LPS, 10 microg/ml) or heat-killed Streptococcus pneumoniae (10(7)cfu/ml) and measured IL-10 mRNA by RT-PCR . Following S . pneumoniae stimulation, PBMC with the ATA haplotype had higher IL-10 mRNA levels than those with the GCC haplotype at 4 h (independent t-test; P=0.024), or the ACC haplotype at 4 h ( P<0.0001) and 8 h ( P=0.007) . Following LPS stimulation, IL-10 mRNA levels were not significantly influenced by the IL10 haplotype, but similar trends were observed, consistent with the variable outcome of published studies . The results suggest that the -819 and/or -592 alleles affect transcription.

J Clin Microbiol, 2003 Nov, 41(11), 5288 - 90
Infections in international pregnancy study: performance of the optical immunoassay test for detection of group B streptococcus; Thinkhamrop J et al.; We evaluated the Strep B optical immunoassay (OIA; ThermoBiostar, Inc.) for detecting light and heavy group B streptococcus colonization in 1,306 pregnant women . The women were examined at 20 to 32 weeks gestation and were from six countries . Compared to culture, the sensitivity and specificity of OIA were 13.3 and 98.4%, respectively, for light colonization and 41.5 and 97.7%, respectively, for heavy colonization.

J Clin Microbiol, 2003 Nov, 41(11), 5285 - 7
Prevalence of group A streptococcal carriers in asymptomatic children and clonal relatedness among isolates in Malatya, Turkey; Durmaz R et al.; In our study, the prevalence of nasopharyngeal Streptococcus pyogenes was 130 (14.3%) of 909 healthy children . Isolates were found to be susceptible to all antibiotics tested . Pulsed-field gel electrophoresis and arbitrarily primed PCR revealed that 34 (32.4%) of the 105 isolates and 41 (40.6%) of the 101 isolates typed, respectively, were clonally indistinguishable.

J Clin Microbiol, 2003 Nov, 41(11), 5282 - 4
Bacitracin-resistant clone of Streptococcus pyogenes isolated from pharyngitis patients in Belgium; Malhotra-Kumar S et al.; We report 16 bacitracin-resistant Streptococcus pyogenes isolates recovered from pharyngitis patients in Belgium, 14 of which belonged to a particular emm type (emm28) . All 16 isolates were constitutively resistant to macrolides and carried erm(B) . The emergence of a bacitracin-resistant S . pyogenes clone raises questions about the continued reliability of bacitracin susceptibility testing for S . pyogenes identification.

J Clin Microbiol, 2003 Nov, 41(11), 4966 - 70
Geographic distribution and clonal diversity of Streptococcus pneumoniae serotype 1 isolates; Brueggemann AB et al.; Serotype 1 pneumococci are a major cause of serious disease and have been associated with outbreaks but are rarely carried . The high attack rate and lack of coverage of this serotype by the heptavalent conjugate vaccine prompted the characterization of a geographically diverse collection of 166 serotype 1 isolates from recent cases of invasive disease . The isolates were resolved by multilocus sequence typing into 16 clones, which clustered into three major lineages with very different geographic distributions . Lineage A isolates were exclusively from Europe and North America, lineage B isolates were predominantly from Africa and Israel, and lineage C isolates were mainly from Chile . There was no clear association between the presence of individual clones within a country and the prevalence of serotype 1 disease.

Laryngoscope, 2003 Nov, 113(11), 2047 - 51
Acute otitis media develops in the rat after intranasal challenge of Streptococcus pneumoniae; Eriksson PO et al.; OBJECTIVES/HYPOTHESIS: The rat is a frequently used animal model for middle ear research . To date, acute otitis media (AOM) has been evoked after instillation of bacteria directly into the middle ear cavity or after traumatizing the tympanic membrane . The purpose of the study was to examine whether, with an intact tympanic membrane and middle ear cavity, intranasally deposited bacteria cause AOM and how tympanic membrane stimulation influences this procedure . STUDY DESIGN: In vivo, murine model . METHODS: In a rat model, Streptococcus pneumoniae, type 3, was intranasally inoculated for 5 consecutive days . The tympanic membrane was treated with saline or with compound 48/80 or was left untreated . The development of AOM was evaluated by otomicroscopy, light microscopy, and middle ear culture . RESULTS: Ninety percent of the ears developed AOM . However, when the tympanic membranes were treated with saline or compound 48/80, only 40% and 57%, respectively, developed AOM . In all, 23 of 40 ears developed AOM and 20 ears showed growth of bacteria . CONCLUSION: Repeated intranasal deposition of S . pneumoniae, type 3, causes AOM in the rat . The development of AOM can be influenced by tympanic membrane stimulation.

Int J Antimicrob Agents, 2003 Nov, 22(5), 541 - 4
Evolution of penicillin and erythromycin co-resistance in Streptococcus pneumoniae in Spain; Garcia-Rey C et al.; The temporal dynamics of penicillin and erythromycin co-resistance in Streptococcus pneumoniae based on two extensive multicentre Spanish surveillance SAUCE studies (1996-1997 and 1998-1999) is presented . Erythromycin resistance among penicillin non-susceptible isolates seems to have reached a limit as evidenced by a null increase between the two surveys, whereas it is growing among penicillin-susceptible pneumococci.

Z Geburtshilfe Neonatol, 2003 Sep-Oct, 207(5), 186 - 9
{Severe late-onset group B streptococcal infection . A case report}; Haase R et al.; BACKGROUND: Group B Streptococcus (GBS) is a well-known cause of neonatal pneumonia, sepsis and meningitis . Peripartal antibiotic prophylaxis for early-onset GBS infection is in routine use since the beginning of the last decade, but strategies for effective prevention of late-onset GBS infections are still lacking . CASE REPORT: Few hours after discharge from a non-local maternity ward a 3-week-old boy was admitted to our hospital because of GBS meningitis with necrotizing encephalomalacia . Maternal mastitis, not a disease of the baby, had led to the first admission . DISCUSSION: Case history and negative maternal swabs and cultures for GBS led to the hypothesis of nosocomial infection . Screening and risk based peripartal antibiotic prophylaxis, better monitoring and improved therapeutic modalities have reduced the incidence and mortality of early-onset GBS infections, but peripartal prophylaxis failed to influence late-onset GBS infections . Up to 40 % of infants with late-onset meningitis develop neurological sequelae . Maternal vaccination with multivalent conjugate vaccines against GBS is a new strategy which may lead to passive protection of the infant . Further studies to examine the efficacy of vaccines are in progress.

J Clin Pathol, 2003 Nov, 56(11), 879 - 81
Corticosteroids as adjunctive treatment in Austrian's syndrome (pneumococcal endocarditis, meningitis, and pneumonia): report of two cases and review of the literature; du Cheyron D et al.; This report describes two cases of Osler's triad of pneumonia, meningitis, and endocarditis, as a result of Streptococcus pneumoniae infection, also called Austrian's syndrome . In the first patient, a 51 year old non-alcoholic man, the aortic valve was affected and needed to be replaced in an emergency operation . The mitral valve was affected in a 70 year old woman without underlying disease, who only benefited from medical treatment . Both patients received corticosteroids, either dexamethasone followed by low doses of hydrocortisone and fludrocortisone, or only hydrocortisone and fludrocortisone, at the onset of the illness, and their outcome was favourable . These case reports focus on the presentation, prognosis, and therapeutic options for this severe syndrome.

Nippon Ganka Gakkai Zasshi, 2003 Oct, 107(10), 590 - 6
{Vitrectomy for endophthalmitis after cataract surgery}; Oshitari K et al.; PURPOSE: To identify risk factors of poor visual outcome with vitrectomy for early-onset endophthalmitis after cataract surgery . PATIENTS AND METHODS: Clinical records of 29 consecutive eyes with endophthalmitis developing within 6 weeks after cataract surgery and that underwent therapeutic vitrectomy between June 1996 and April 2001 were retrospectively reviewed . Twenty-two of the eyes received intravitreal injections of vancomycin and ceftazidime at the time of vitrectomy, and all patients received intravenous antibiotics . Eyes were divided into two groups; group A consisted of 22 eyes with a final visual acuity of 0.2 or greater, and group B consisted of 7 eyes with a final visual acuity of less than 0.2 . RESULTS: Fifteen eyes (52%) in group A achieved a visual acuity of 0.5 or better and 8(28%) achieved a visual acuity of 1.0, while 4 eyes in group B developed phthisis bulbi . For eyes with a preoperative visual acuity of hand motions or worse, there was no correlation between final visual acuity and preoperative visual acuity . The overall culture-positive rate was 57% . In group A, methicillin-resistant Staphylococcus epidermidis was identified in 6 eyes, methicillin-resistant Staphylococcus aureus (MRSA) in 3 eyes and enterococcus in 2 eyes . In group B, alpha-hemolytic streptococcus (AHS) was identified in 4 eyes, aspergillus in 1 eye, and MRSA in 1 eye . All isolates were sensitive to vancomycin with the exception of the aspergillus . AHS infection appeared to be associated with wound failure from the initial cataract surgery and a poor visual outcome . Among 3 of the eyes that developed phthisis bulbi, intravitreal injection of antibiotics was not performed . CONCLUSION: Early vitrectomy and intravitreal injection of vancomycin may improve visual outcomes, but infection with AHS may be associated with cataract surgery wound failure and poor visual outcomes.

Arch Oral Biol, 2003 Dec, 48(12), 815 - 24
A 100 kDa vanadate and lanzoprazole-sensitive ATPase from Streptococcus mutans membrane; Magalhaes PP et al.; The cariogenic potential of Streptococcus mutans is due to the production of organic acids derived from energy metabolism, which implies the need of mechanisms for the organism to tolerate this acidic environment . The F(1)F(o)-ATPase is generally considered as the main enzyme responsible for cytoplasmic proton extrusion, but mutations that resulted in a 50% reduction in F(1)F(o)-ATPase activity in S . mutans still allowed the micro-organism to grow and extrude acid, keeping the intracellular pH one pH unit above the extracellular ambient . This finding suggests the existence of other enzymatic (or cellular) mechanisms that keep the cytosolic pH neutral during micro-organism growth . This paper describes a membrane protein in S . mutans, with a molecular weight of 100 kDa, which exhibits ATPase activity inhibited by classic inhibitors of P-type ATPases (orthovanadate) and H(+),K(+)-ATPase (lanzoprazole), has an optimum pH comparable to other H(+)-ATPases and undergoes phosphorylation during the catalytic reaction, like that of H(+)-ATPases described in yeast and plant plasma membrane . Together, these results strongly suggest that the enzyme we describe here is a P-type H(+)-ATPase or H(+),ion-ATPase that can act in association with F(1)F(o)-ATPase during the growth of the S . mutans.

Pediatrics, 2003 Nov, 112(5), 1095 - 102
Streptococcus pneumoniae infections in the neonate; Hoffman JA et al.; OBJECTIVE: Streptococcus pneumoniae infections in the neonate (SPIN) are relatively unusual events (1%-11% of neonatal sepsis) but are associated with substantial morbidity and mortality . Previous reports suggest that invasive SPIN is associated with prolonged rupture of membranes, maternal colonization/illness, prematurity, early-onset pneumonia presentation (<72 hours), and high mortality (50%) . The aim of this study was to review the current epidemiology and clinical course of SPIN . METHODS: The US Pediatric Multicenter Pneumococcal Surveillance Group has been prospectively monitoring S pneumoniae infections since 1993 in 8 children's hospitals . For this report, data were gathered retrospectively from the charts of neonates who were 30 days of age and younger and had SPIN from September 1993 to February 2001 . All pneumococcal isolates were sent to a central laboratory for serogrouping/typing and susceptibility testing . RESULTS: Twenty-nine cases of SPIN were identified from a total of 4428 episodes of S pneumoniae infection in children . Sixty-six percent were male, and 55% were white; the mean age was 18.1 day (+/-8.2) . Ninety percent of infants were >or=38 weeks' gestation . Two mothers had bacterial infections at delivery; 1 had S pneumoniae isolated from both blood and cervix, and 1 had clinical amnionitis . The primary diagnoses in the neonates were bacteremia (8), meningitis (8), bacteremic pneumonia (4), septic arthritis/osteomyelitis (1), and otitis media (8) . Thirty percent of infants with invasive SPIN presented with leukopenia/neutropenia, but this did not predict poor outcome . The infecting pneumococcal serogroups were 19 (32%); 9 (18%); 3 and 18 (11% each); 1, 6, and 14 (7% each); and 5 and 12 (3.5% each) . Twenty-six percent of invasive neonatal infections were caused by serogroups 1, 3, 5, and 12, which are not contained in the heptavalent pneumococcal vaccine . In contrast, 6% of invasive nonneonatal disease was caused by these same nonvaccine serogroups . Susceptibility testing demonstrated that 21.4% of isolates were penicillin nonsusceptible and 3.6% were ceftriaxone nonsusceptible . Three (14.3%) neonates with invasive SPIN died; all deaths occurred within 36 hours of presentation . Deaths did not appear to be related to pneumococcal serogroup or susceptibilities . CONCLUSIONS: Compared with previous studies of neonates with pneumococcal infection, this series showed that infants with SPIN were usually 2 to 3 weeks of age at presentation; likely to be full term; and ill with pneumonia, meningitis, and otitis media . This late-onset presentation was associated with an overall mortality rate of 10.3% (14.3% for invasive disease).

J Bacteriol, 2003 Nov, 185(22), 6640 - 7
MgrA, an orthologue of Mga, Acts as a transcriptional repressor of the genes within the rlrA pathogenicity islet in Streptococcus pneumoniae; Hemsley C et al.; Streptococcus pneumoniae normally resides in the human nasopharynx in a nondisease state . In response to unknown triggers this organism can descend to the lower respiratory tract and/or invade the bloodstream . Regulation and activation of virulence genes play essential roles in this process of disease development . Characterization of S . pneumoniae regulatory networks has been a recent area of interest, but despite inroads little is known about regulation of virulence genes in this pathogen . A putative transcriptional regulator in S . pneumoniae, mgrA, which exhibits homology to the virulence gene activator mga of group A streptococcus, was previously identified as a regulator that is required for development of pneumonia in a murine model . In this study we confirmed that mgrA plays a role in both nasopharyngeal carriage and pneumonia . Transcriptional profiling by microarray technology was used to show that mgrA acts as a repressor of the previously characterized rlrA pathogenicity islet . This is manifested phenotypically by a decrease in adherence to epithelial cells in tissue culture since the rlrA pathogenicity islet contains genes mediating adherence.

J Bacteriol, 2003 Nov, 185(22), 6592 - 9
MtaR, a regulator of methionine transport, is critical for survival of group B streptococcus in vivo; Shelver D et al.; The group B streptococcus (GBS) is an important human pathogen that infects newborns as well as adults . GBS also provides a model system for studying adaptation to different host environments due to its ability to survive in a variety of sites within the host . In this study, we have characterized a transcription factor, MtaR, that is essential for the ability of GBS to survive in vivo . An isogenic strain bearing a kanamycin insertion in mtaR was attenuated for survival in a neonatal-rat model of sepsis . The mtaR mutant grew poorly in human plasma, suggesting that its utilization of plasma-derived nutrients was inefficient . When an excess of exogenous methionine (200 microg/ml) was provided to the mtaR mutant, its growth rate in plasma was restored to that of the wild-type strain . The mtaR mutant grew poorly in chemically defined medium (CDM) prepared with methionine at a concentration similar to that of plasma (4 microg/ml) but was able to grow normally in CDM prepared with a high concentration of methionine (400 microg/ml) . Both the wild-type strain and the mtaR mutant were incapable of growth in CDM lacking methionine, indicating that GBS cannot synthesize methionine de novo . When the abilities of the strains to incorporate radiolabeled methionine were compared, the mtaR mutant incorporated fivefold less methionine than the wild-type strain during a 10-min period . Collectively, the results from this study suggest that the ability to regulate expression of a methionine transport system is critical for GBS survival in vivo.

Blood, 2004 Mar 1, 103(5), 1702 - 9 Epub 2003 Oct 30.
Thrombomodulin mutant mice with a strongly reduced capacity to generate activated protein C have an unaltered pulmonary immune response to respiratory pathogens and lipopolysaccharide; Rijneveld AW et al.; The thrombomodulin-protein C-protein S (TM-PC-PS) pathway exerts anticoagulant and anti-inflammatory effects . We investigated the role of TM in the pulmonary immune response in vivo by the use of mice with a mutation in the TM gene (TM(pro/pro)) that was earlier found to result in a minimal capacity for activated PC (APC) generation in the circulation . We here demonstrate that TM(pro/pro) mice also display a strongly reduced capacity to produce APC in the alveolar compartment upon intrapulmonary delivery of PC and thrombin . We monitored procoagulant and inflammatory changes in the lung during Gram-positive (Streptococcus pneumoniae) and Gram-negative (Klebsiella pneumoniae) pneumonia and after local administration of lipopolysaccharide (LPS) . Bacterial pneumonia was associated with fibrin(ogen) depositions in the lung that colocalized with inflammatory infiltrates . LPS also induced a rise in thrombin-antithrombin complexes in bronchoalveolar lavage fluid . These pulmonary procoagulant responses were unaltered in TM(pro/pro) mice, except for enhanced fibrin(ogen) deposition during pneumococcal pneumonia . In addition, TM(pro/pro) mice displayed unchanged antibacterial defense, neutrophil recruitment, and cytokine/chemokine levels . These data suggest that the capacity of TM to generate APC does not play a role of importance in the pulmonary response to respiratory pathogens or LPS.

Vet Immunol Immunopathol, 2003 Dec 15, 96(3-4), 193 - 205
Dynamics of leukocytes and cytokines during experimentally induced Streptococcus uberis mastitis; Rambeaud M et al.; Streptococcus uberis causes a significant proportion of clinical and subclinical intramammary infections (IMI) in lactating and non-lactating dairy cows . In spite of this, its pathogenesis is incompletely understood . A study was conducted to determine leukocyte and cytokine dynamics during experimentally induced S . uberis mastitis . Five Jersey and five Holstein cows were challenged via intramammary inoculation of S . uberis into two uninfected mammary glands . Sixteen of 20 challenged mammary glands developed clinical mastitis with peak clinical signs observed at 144 h . The number of S . uberis in milk increased (P<0.05) 48 h after challenge, in spite of an increase in milk somatic cells that began at 18 h (P<0.001) and remained elevated throughout the study . Increased tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-8 (IL-8) in milk were detected 66 h after challenge (P<0.05) . Peak TNF-alpha and IL-8 concentrations occurred 120 h after challenge and preceded peak clinical signs . Experimental S . uberis IMI induced local production of TNF-alpha, IL-1beta and IL-8, which may play a role in the pathogenesis of S . uberis mastitis . Other mediators may be involved in initial leukocyte recruitment to the mammary gland, since increases in milk somatic cells occurred earlier than cytokine production.

Arch Biochem Biophys, 2003 Nov 15, 419(2), 147 - 57
Analysis of recombinant acylated pneumococcal surface adhesin A of Streptococcus pneumoniae by mass spectrometry; De BK et al.; Streptococcus pneumoniae pneumococcal surface adhesin A (PsaA) is a species-common, immunogenic surface lipoprotein . In this study, the psaA gene was expressed as a nonfusion acylated protein in an Escherichia coli expression system . Yields of pure recombinant PsaA (rPsaA) were 8-10 mg/liter of fermentation culture . Analysis of rPsaA tryptic digests by HPLC-electrospray mass spectrometry (MS) confirmed 98% of the expected protein sequence . GC/MS data demonstrated very similar acylation of native and rPsaA by C12:0-C22:0 fatty acids, with C16 and C18 predominating . Negative ion electrospray MS/MS analysis of the rPsaA lipid anchor released by Pronase-E confirmed that the structure was based on an N-terminal palmitoylcysteine (Pam(3)Cys) . Electrospray MS heterogeneity analysis of intact rPsaA indicated that all of the observed heterogeneity could be accounted for by the fatty acid distributions . The availability of well-characterized rPsaA will facilitate the continued research and development of protein-based vaccines for the prevention of pneumococcal disease.

Curr Biol, 2003 Oct 28, 13(21), 1858 - 66
The B cell SH2/PH domain-containing adaptor Bam32/DAPP1 is required for T cell-independent II antigen responses; Fournier E et al.; BACKGROUND: Bam32/DAPP1 is a B cell adaptor composed of both a PH and an SH2 domain . Previous studies in cell culture and chicken DT40 cells have indicated that Bam32 is critical for normal signaling downstream of the B cell receptor (BCR) . RESULTS: We now study the function of Bam32 in mice in which Bam32 has been disrupted by a viral gene trap approach . Although B and T cell development is normal in Bam32(-/-) mice, B cell proliferation is reduced by about 50% after BCR crosslinking when compared with Bam32(+/+) mice . Differences in the activation of Erk, Jnk and p38 Map kinases, PLCgamma, and Ca(2+) flux do not account for the defect in proliferation as activation was similar in Bam32(+/+) and Bam32(-/-) B cells . Interestingly, whereas antibody response to T-dependent (TD) and T-independent (TI)-I antigens was similar between Bam32(+/+) and Bam32(-/-) mice, TI-II responses were defective in Bam32(-/-) mice; Bam32(-/-) mice failed to undergo isotype class switch recombination (CSR) to produce IgG3 antibodies due to a cell-autonomous defect in generation of IgG3 germline transcripts . The defect in TI-II antigen response led to an impaired antibody response to immunization with type 3 Streptococcus pneumoniae capsular polyschaccharide (PS), resulting in a markedly increased susceptibility to infection by Streptococcus pneumoniae . CONCLUSIONS: These findings indicate that Bam32 specifically couples an upstream signal to the IgG3 isotype heavy chain CSR and suggest that defects in Bam32 may account for the increased susceptibility to encapusulated organisms in a subset of immunodeficient patients.

J Coll Physicians Surg Pak, 2003 Oct, 13(10), 573 - 6
Mortality variables in pyogenic meningitis in paediatric age group; Khichi GQ et al.; OBJECTIVE: To determine the association of the studied variables on mortality in pyogenic meningitis in paediatric age group . DESIGN: An observational analytical study . PLACE AND DURATION OF STUDY: Paediatrics Medicine, Unit-2 of B.V . Hospital, attached with Quaid-e-Azam Medical College, Bahawalpur, from December 2000 to December 2002 . PATIENTS AND METHODS: Sample size was 300 admitted cases of pyogenic meningitis, aged 2 months to 12 years, meeting the inclusion criteria . The association of the different variables with mortality in pyogenic meningitis was studied . Data was collected and tabulated . X2 test of significance was applied to determine the p-value . p<0.05 was taken as statistically significant . RESULTS: The mortality rate was 10% (30/300) . The association of different variables, with outcome at the time of admission was statistically significant in prolonged duration of illness (chronicity prior to admission and increased cerebrospinal fluid (CSF) neutrophils after 1st lumbar puncture . Among the etiological microorganisms isolated from culture of CSF, only Streptococcus pneumoniae had statistically significant association . CONCLUSION: Mortality in pyogenic meningitis was significantly related to pre-admission illness duration and CSF neutrophilia . Mortality can be reduced by early and appropriate recognition . Antibiotic and supportive therapy should be initiated promptly followed by specific medication when the reports of the CSF culture is available.

Surg Infect (Larchmt), 2003 Fall, 4(3), 255 - 62
In vitro antimicrobial activity of oxidized regenerated cellulose against antibiotic-resistant microorganisms; Spangler D et al.; BACKGROUND: The emergence of multi-drug resistant microorganisms presents a critical problem for patients undergoing surgery . Acidic pH, which is produced by oxidized regenerated cellulose (ORC), is a broad-spectrum physiological detriment to survival of microorganisms known to cause surgical infections . The purpose of this study was to examine the antimicrobial effect of ORC against antibiotic-resistant organisms . METHODS: ORC products were challenged with ATCC reference strains and clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), vancomycin-resistant Enterococcus (VRE), penicillin-resistant Streptococcus pneumoniae (PRSP), and non-resistant ATCC strains of S . aureus and Pseudomonas aeruginosa . Samples of three ORC products (SURGICEL absorbable hemostat, SURGICEL Fibrillar absorbable hemostat, and SURGICEL NU-KNIT absorbable hemostat and identified, respectively, as ORC-R, ORC-F, and ORC-N for this study) were inoculated with challenge organisms in nutrient broth to produce a weight to volume ratio of 15 mg ORC/mL . Plate counts were performed at 0, 1, 6, and 24 h . RESULTS: Antimicrobial activity was seen with all three ORC products against the challenge organisms . Data indicate that antibiotic-resistant microorganisms remain susceptible to the antimicrobial activity of ORC . In testing with nine of 10 bacteria, including four antibiotic-resistant clinical isolates (VRE, MRSA, and PRSP) three-log or greater reductions were seen at 24-h exposure . One ATCC strain of VRE demonstrated some level of resistance to the acidic pH effect . ORC-N showed a three-log reduction with this organism, whereas the reductions with ORC-R and ORC-F were less than one log . CONCLUSION: Since low pH affects a relatively broad-spectrum of bacteria and does not act in a mechanism-specific manner, as do antibiotics, antibiotic-resistant strains of bacteria are unlikely to resist the ORC pH effect . Results of this in vitro assessment support the hypothesis that the antimicrobial activity of ORC is effective against antibiotic-resistant microorganisms.

J Oral Maxillofac Surg, 2003 Oct, 61(10), 1156 - 61
The presence of bacteria in the synovial fluid of the temporomandibular joint and clinical significance: preliminary study; Kim SJ et al.; PURPOSE: The objective of this study was to find any relation between the presence of specific bacterial species in the synovial fluid of the temporomandibular joint (TMJ) and clinical parameters . PATIENTS AND METHODS: We studied 43 patients (male-to-female ratio, 1:1.69; average age, 34.37 +/- 14.55 years) . Thirty-three patients had a displaced disc in the TMJ (DD group), and 10 patients did not have a displaced disc of the TMJ or any symptom related to TMJ disorders (NDD group) . Clinical examinations were made to determine maximum mouth opening, joint sounds, previous trauma history, systemic disease, and TMJ pain . Six bacterial species that were reported in other studies were chosen to evaluate the presence of bacteria in the TMJ for this study . RESULTS: Mycoplasma genitalium was most frequently detected in synovial fluid (86.0%) . Staphylococcus aureus, Mycoplasma fermentans/orale, Actinobacillus actinomycetemcomitans, and Streptococcus mitis were detected in 51.2%, 37.2%, 25.6%, and 7.0% of samples, respectively . beta-Hemolytic Streptococcus was not detected . The prevalence of S aureus was significantly higher in the DD group than in the NDD group (P <.05) . The patients who had M . fermentans/orale were 5.40 times more likely to be younger than 30 years than were those without M . fermentans/orale (P <.05) . Those with M . genitalium were 5.81 times more likely to be female than were those without M . genitalium (P <.05) . CONCLUSION: The presence of S . aureus in TMJ synovial fluid was related to TMJ disorder symptoms and clinical parameters seemed to be influenced by bacterial presence in TMJ synovial fluid.

J Antimicrob Chemother, 2003 Dec, 52(6), 944 - 52 Epub 2003 Oct 29.
Worldwide incidence, molecular epidemiology and mutations implicated in fluoroquinolone-resistant Streptococcus pneumoniae: data from the global PROTEKT surveillance programme; Canton R et al.; OBJECTIVES: To analyse the mutations and epidemiology associated with fluoroquinolone-resistant pneumococci collected as part of the PROTEKT global surveillance programme during 1999-2000 . METHODS: Sixty-nine centres in 25 countries submitted a total of 3362 Streptococcus pneumoniae isolates, for which the MICs of antimicrobial agents were determined using NCCLS methodology . RESULTS: Levofloxacin resistance was low overall (1% worldwide), with higher rates in: Hong Kong (14.3%), South Korea (2.9%), USA (1.8%), Mexico (1.5%), Canada (1.4%) and Japan (1.3%) . Levofloxacin resistance was very low or absent in European countries, and absent in Australia . Worldwide, there was a total of 35 levofloxacin-resistant isolates, of which 22 (63%) were resistant and 10 (29%) were intermediate to moxifloxacin . All levofloxacin-resistant isolates were susceptible to telithromycin (< or =0.5 mg/L), linezolid (< or =2 mg/L) and quinupristin/dalfopristin (< or =1 mg/L) . One or more mutations in the topoisomerase genes were identified in all levofloxacin-resistant isolates; most of these isolates (33/35) had a mutation in one of the DNA gyrase encoding genes (gyrA, gyrB) and one of the topoisomerase IV encoding genes (parC, parE) . Eighteen (51%) isolates carried the same combination of amino acid substitutions: Ser-81-->Phe in GyrA and Ser-79-->Phe in ParC . Isolates displaying a levofloxacin MIC of 2-4 mg/L generally had no mutation or one mutation in either a DNA gyrase or a topoisomerase IV gene, although most mutations were in parC . CONCLUSIONS: Most levofloxacin-resistant isolates possess two mutations (one in DNA gyrase and one in topoisomerase IV) . Although multilocus sequence typing demonstrated that most of these isolates were unrelated, 12 (34%) were the Spain23F-1 clone: 10 from Hong Kong and one each from Saskatchewan, Canada and Sao Paulo, Brazil.

J Antimicrob Chemother, 2003 Dec, 52(6), 953 - 60 Epub 2003 Oct 29.
Emergence of a fluoroquinolone-resistant strain of Streptococcus pneumoniae in England; Johnson AP et al.; OBJECTIVE: To determine the epidemiological relationship between pneumococci of serotype 9V, with reduced susceptibility to ciprofloxacin, penicillin and erythromycin, referred to the Reference Laboratory during 1997-2001 . METHODS: Isolates were characterized by multilocus sequence typing (MLST), PFGE, and sequencing of parC and gyrA . Relevant clinical data were sought . RESULTS: Forty-eight isolates were received from nine laboratories in England, but 35 (73%) were from one laboratory in Birmingham, and were mostly from elderly patients receiving ofloxacin or ciprofloxacin for respiratory infections . There were two quinolone resistance phenotypes, with ciprofloxacin, moxifloxacin and gemifloxacin MICs of 8-32, 0.5-1 and 0.125-0.25 mg/L, and 64-256, 4-16 and 1-4 mg/L, respectively . Each of three isolates from the former group had mutations in parC, whereas each of nine isolates from the more resistant group had mutations in both parC and gyrA . Several also had increased quinolone efflux . Typing of 27 quinolone-resistant isolates showed that eight were indistinguishable from the epidemic Spain9V-3 (ST156) clone, while the remainder belonged to a novel but related type (ST609), that differed from Spain9V-3 at 2/7 alleles (2 bp changes in aroE and 1 bp change in gdh) . Both MLST types were represented among isolates with high- and low-level quinolone resistance . Three of five serotype 9V isolates from Birmingham, with reduced susceptibility to penicillin and erythromycin, and ciprofloxacin MICs of 1-2 mg/L, belonged to MLST type ST609, while another was indistinguishable from the Spain9V-3 clone . Review of records of 32 patients from Birmingham indicated that some isolates were nosocomial, whereas others were acquired in the community . CONCLUSIONS: In the late 1990s, a quinolone-resistant strain, clonally related to Spain9V-3, emerged in England, principally in Birmingham.

Cochrane Database Syst Rev . 2003;(4):CD000422.
Vaccines for preventing pneumococcal infection in adults; Dear K et al.; BACKGROUND: Diseases caused by Streptococcus pneumoniae (S . pneumoniae) continue to cause substantial morbidity and mortality throughout the world . Polysaccharide pneumococcal vaccines have been developed for over 50 years and may have the potential to prevent disease and death . OBJECTIVES: To assess the effectiveness of polysaccharide pneumococcal vaccination in preventing disease or death in adults . SEARCH STRATEGY: Trials were identified by electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) issue 2, 2003 (which includes the Cochrane ARI Group's specialised register); MEDLINE (January 1966 to June 2003); and EMBASE (1974 to June 2003) . We searched existing literature . The bibliographies of all newly revealed studies were read in order to identify further studies . The vaccine manufacturers, the lead authors of newly identified studies not included in existing meta-analyses were contacted . SELECTION CRITERIA: A) Prospective, randomised or quasi-randomised studies comparing pneumococcal vaccines with placebo, control vaccines or no intervention.B) Case-control studies (including indirect cohort studies) assessing pneumococcal vaccine effectiveness against invasive pneumococcal disease . Cohort studies are excluded . DATA COLLECTION AND ANALYSIS: A) Randomised studies . Trial quality assessment was conducted by two reviewers (JH and DT) . Data extraction was done by three reviewers (JH, DT, KD) . There were many instances of unclear or incomplete data in the trial reports, and the final dataset was arrived at after much deliberation and discussion, including comparison with the data used in two previous reviews of this question . Due to the age of the trials (dating back to 1954 in one case) it was not generally possible to obtain clarification from the authors, though a partial clarification was achieved in one case.B) Non-randomised studies . Study quality was assessed by two reviewers (RA and KD) . MAIN RESULTS: The combined results from the randomised studies fail to show that the polysaccharide pneumococcal vaccine is effective in preventing either pneumonia (outcome 6: odds ratio = 0.77, confidence interval 0.58, 1.02, number = 14) or death (outcome 8: odds ratio 0.90, confidence interval 0.76, 1.07, number = 11) . Despite encouraging data from some very early trials, pooling trials published from 1977 on suggests there is no effect (outcome 6; odds ratio = 0.96, confidence interval 0.80, 1.15, number = 12; outcome 9: odds ratio = 0.98, confidence interval 0.88, 1.09, number = 10) . The available data cannot distinguish whether this heterogeneity in results is due to improvements in trial methodology and reporting, to differences in trial setting or to real loss of efficacy over time . This is because the early, poorly reported trials were conducted in high-risk healthy populations where the expected benefit is greatest.The case-control studies show significant efficacy in preventing invasive pneumococcal disease: OR 0.47 (CI 0.37, 0.59) corresponding to an efficacy of 53% . REVIEWER'S CONCLUSIONS: While polysaccharide pneumococcal vaccines do not appear to reduce the incidence of pneumonia or death in adults with or without chronic illness, or in the elderly (55 years and above), the evidence from non-randomised studies suggests that the vaccines are effective in the reducing the incidence of the more specific outcome, invasive pneumococcal disease, among adults and the immunocompetent elderly (55 years and above) . Surveillance data suggest that infection rates vary widely between and also within countries, but a typical figure in developed countries is 0.01%, or 10 per 100,000 per year . Efficacy of 50% then corresponds to a number-needed-to-treat (NNT) of 20,000 vaccinations per infection avoided, and perhaps 50,000 per death avoided.

Clin Infect Dis, 2003 Nov 15, 37(10), 1335 - 9 Epub 2003 Oct 13.
Pneumonia in older persons; Loeb M; Community-acquired pneumonia (CAP) is an important threat to the health of older adults . Streptococcus pneumonia remains the most important cause of CAP . Risk factors for CAP include alcoholism, asthma, immunosuppression, chronic respiratory or cardiac disease, institutionalization, and increasing age . Residents of long-term care facilities--a distinct subpopulation of elderly people--are at particularly high risk for developing pneumonia . In this setting, swallowing difficulties, witnessed aspiration, and receipt of sedatives are potentially modifiable risk factors . The clinical presentation in elderly patients is characterized by a reduced prevalence of nonrespiratory symptoms . Few randomized, controlled trials of therapy exist for elderly persons living in the community or in a long-term care setting . Good evidence exists to support the annual administration of influenza vaccine to older adults . Although evidence in clinical trials differs from evidence in observational studies that demonstrate clear benefits associated with the polysaccharide pneumococcal vaccine in this population, the vaccine is recommended for adults aged

J Zoo Wildl Med, 2003 Sep, 34(3), 296 - 301
A third report of "golf ball disease" in an Amazon River dolphin (Inia geoffrensis) associated with Streptococcus iniae; Bonar CJ et al.; An Amazon River dolphin (Inia geoffrensis) developed a dermatologic syndrome characterized by the occurrence of slow-growing, nodular, s.c . abscesses . Initial biopsies, cultures, and cytologic analysis of needle aspirates from the abscesses indicated steatitis with probable secondary, gram-negative bacterial infection . Treatment with dietary vitamin E supplement and broad-spectrum antibiotics yielded minimal improvement . Subsequent cultures revealed Streptococcus iniae in addition to several gram-negative bacteria . Vigorous surgical management of the abscesses, including lancing, debridement, and irrigation, combined with antimicrobial therapy specific for Streptococcus and gram-negative organisms, and improvement of the animal's diet and environmental water quality led to gradual recovery . When the animal was ill, it demonstrated an inflammatory leukogram and transient uremia . Streptococcus iniae is a serious pathogen of aquacultured fishes and humans and should be included in the differential diagnosis of chronic dermatopathy in river dolphins . Specific antimicrobial therapy, excellent water quality, surgical management of abscesses, and adherence to sanitary protocols should be observed in cases of suspected S . iniae infection in dolphins.

Scand J Plast Reconstr Surg Hand Surg, 2003, 37(4), 239 - 42
Necrotising fasciitis and myositis that originated from gastrointestinal bacterial infection: two fatal cases; Fujioka M et al.; We present two cases of aggressive myofasciitis after gastrointestinal infections . The first patient developed necrosis of the legs over 5 days and he died on the 20th day . Vibrio vulnificus was cultured . The second patient developed bullae on his thigh and he died the next day . Streptococcus pyogenes was cultured.

Acta Odontol Scand, 2003 Aug, 61(4), 241 - 6
Antimicrobial effects of glass ionomer cements containing bioactive glass (S53P4) on oral micro-organisms in vitro; Yli-Urpo H et al.; The antimicrobial effects of two glass-ionomer cements (GICs), GC Fuji II and Fuji II LC, mixed with different amounts (0 wt%, 10 wt% and 30 wt% of the total powder weight) of bioactive glass (BAG), S53P4, on Streptococcus mutans and Candida albicans were studied in vitro . The growth inhibition was tested using agar diffusion . The materials were also studied in a liquid media . The effect of the material extracts on acid production was studied using cell suspensions . The antimicrobial activity of the materials was examined by incubating the cell suspensions with the material powder . In the agar diffusion test, only the GICs containing 30 wt% BAG inhibited the growth of S . mutans . When the materials were tested in culture medium, no inhibitory effects on S . mutans were detected . The only materials to inhibit acid production of S . mutans were the GIC extracts without added BAG . Furthermore, they also had antibacterial activity against S . mutans when tested as powders . We found very few effects of the tested materials on C . albicans . The only material with an antimicrobial effect on C . albicans was BAG when incubated in a suspension with C . albicans . This is the first time that this effect has been demonstrated for C . albicans . By adding BAG to GICs the structure of the material becomes more brittle than the structure of GICs without BAG . Thus, in addition to the composition of the tested materials, their structure may also have influenced the results . In summary, commercially available GICs and GIC disks containing 30 wt% of BAG exerted antibacterial effects on S . mutans . BAG exerted antimicrobial effects on both S . mutans and C . albicans.

J Microbiol Immunol Infect, 2003 Sep, 36(3), 175 - 81
Rate of nasopharyngeal carriage, antimicrobial resistance and serotype of Streptococcus pneumoniae among children in northern Taiwan; Lo WT et al.; Multiple-antibiotic-resistant strains of Streptococcus pneumoniae are isolated from clinical specimens in Taiwan with increasing frequency . This study aimed to define the carriage rate of S . pneumoniae among children in northern Taiwan, and to determine the antibiotic susceptibility and the serotype incidence of these isolates . Nasopharyngeal swabs were taken from a total of 478 children (age, 1 month-14 years) who sought medical care only for non-infectious disease or routine vaccination at our hospital between July 1998 and November 1999 . S . pneumoniae was isolated from 95 patients, and the collected isolates were available for analysis . All pneumococcal isolates were serotyped and their antimicrobial susceptibility tested by standard methods . The total rate of pneumococcal carriage in the study population was 19.9% and the isolation rate was higher in children aged between 2 and 5 years . Only 10 (10.5%) of the isolates were susceptible to penicillin (minimum inhibitory concentration {MIC}, < or = 0.06 microg/mL); 47 (49.5%) isolates were intermediately resistant (MIC, 0.12-1 microg/mL) and 38 (40%) were highly resistant (MIC, > or = 2 microg/mL) . Among the 95 S . pneumoniae isolates, the common serotypes were 23F (22%), 6B (18.9%), 19F (18.9%), and 14 (8.4%) . Evaluation of the results showed that serotypes 23F (24.7%), 19F (21.2%), 6B (15.3%), and 14 (9.4%) composed 70.6% of all penicillin-non-susceptible S . pneumoniae isolates . The significant rate of isolation of penicillin-non-susceptible S . pneumoniae from children indicates that both the judicious use of antibiotics and the availability of conjugate pneumococcal vaccines are the most appropriate strategy to reduce the carriage of resistant pneumococci.

Indian Pediatr, 2003 Oct, 40(10), 1002 - 4
Varicella complicated by scarlet fever; Yavuz T et al.; We report a 3-year-old boy with varicella complicated by cellulitis and scarlet fever . He developed a typical rash of scarlet fever following the onset of varicella . Streptococcus pyogenes was isolated from the ulcers due to varicella . The present case suggests that scarlet fever may rarely develop following varicella and should be considered in children with complicated varicella.

Int J Food Microbiol, 2003 Dec 15, 89(1), 77 - 83
Inhibition of Listeria monocytogenes by bovicin HC5, a bacteriocin produced by Streptococcus bovis HC5; Mantovani HC et al.; Cattle can be infected with Listeria monocytogenes by consuming contaminated plant materials, soil or silage, and farmers have sought ways of preventing this contamination . Recent work indicated that Streptococcus bovis HC5 produced a bacteriocin (bovicin HC5) that could inhibit a variety of gram-positive bacteria, and we examined the ability of bovicin HC5 to inhibit 10 strains of L . monocytogenes that had been isolated from plant materials, soil, silage and infected cattle . Growth experiments indicated that all of the L . monocytogenes strains were inhibited by 100 activity units (AU) of bovicin HC5 ml(-1) . L . monocytogenes cultures that were transferred with sublethal doses (12.5 AU ml(-1)) could be adapted in stepwise fashion to higher doses of bovicin HC5 . However, even 'adapted' cultures did not grow if 400 AU ml(-1) was added . The effect of bovicin HC5 on L . monocytogenes was bactericidal, and viability decreased 5-7 logs after only 2 h of exposure . Bovicin HC5 caused a nearly complete efflux of intracellular potassium in 15 min but only if the pH was less than 6.0 . When the pH was greater than 6.0, the cells maintained their potassium pool . L . monocytogenes cells that were acid-adapted (final pH of 4.6) were as sensitive to bovicin HC5 as those that were not acid-adapted (final pH of 6.3) . These results support the idea that bovicin HC5 could be effective in controlling listeria in contaminated silages.

Clin Chem, 2003 Nov, 49(11), 1839 - 45
Apolipoprotein C-III isofocusing in the diagnosis of genetic defects in O-glycan biosynthesis; Wopereis S et al.; BACKGROUND: Defects in the biosynthesis of N-glycans may be found by isoelectric focusing (IEF) of plasma transferrin . No test is available to demonstrate O-glycan biosynthesis defects . METHODS: We used isoforms of apolipoprotein C-III (apoC-III) as a marker for the biosynthesis of core 1 mucin type O-glycans . Plasma samples from patients with primary defects and secondary alterations in N-glycan biosynthesis were studied by apoC-III isofocusing . RESULTS: Age-related reference values for apoC-III were determined . Plasma samples from patients with the primary congenital disorders of glycosylation (CDG) types Ia-Ic, Ie, If, IIa, and IId all showed a normal apoC-III isofocusing profile . Plasma from two patients with CDG type IIx were tested: one showed a normal apoC-III distribution, whereas the other showed a hypoglycosylation profile . In plasma from patients with hemolytic uremic syndrome (HUS), a hypoglycosylation profile was obtained . CONCLUSIONS: IEF of apoC-III is a rapid and simple technique that may be used as a screening assay for abnormalities in core 1 mucin type O-glycans . Evidence that a patient in this study has a primary genetic defect affecting both N- and O-glycosylation provides the first example of an inborn error of metabolism affecting the biosynthesis of core 1 mucin type O-glycans . Our data narrow the options for the position of the primary defect in this patient down to a step in the biosynthesis, activation, or transfer of galactose or N-acetylneuraminic acid to both N- and O-glycans . Circulating neuraminidase excreted by Streptococcus pneumoniae caused the high percentage of asialo apoC-III in two HUS patients.

Nippon Jibiinkoka Gakkai Kaiho, 2003 Sep, 106(9), 884 - 7
{A case of cervical necrotizing soft tissue infection}; Udaka T et al.; We treated a 62-year-old woman with a cervical necrotizing soft tissue infection of the Streptococcus milleri group . Numerous spot gas images were recognized from the right pharynx to the neck in CT at initial diagnosis, but we chose conservative treatment because abscess findings were not clear . The inflammation improved temporarily, but we operated through an outside incision because symptoms recurred and cervical skin became necrotic after one week . Inside, the fascia were necrotic and an abscess extended from the precordia to the left upper arm and the right axillary region . The cervical skin defect was restored in due course in about 2 months and cured without mediastinitis or sepsis developing . The S . milleri group was detected in pus . A cervical necrotizing soft tissue infection does not form an abscess mainly in one space as does a normal deep neck infection and invades fascia space rapidly and widely . We took this disease into consideration and had to intervene surgical rather soon . A review of this case and the literature indicates that the S . milleri group may have become an important pathogen in cervical necrotizing soft tissue infection.

Antimicrob Agents Chemother, 2003 Nov, 47(11), 3637 - 9
Genetic relatedness of recently collected Spanish respiratory tract Streptococcus pneumoniae isolates with reduced susceptibility to amoxicillin; Perez-Trallero E et al.; Of Streptococcus pneumoniae isolates from 17 hospitals, 9.8% were amoxicillin nonsusceptible (MIC > or = 4 microg/ml) . The genetic relatedness of 138 isolates was studied by pulsed-field gel electrophoresis . Although 44 different clones were detected, more than 62% of these isolates were related to four clones (Spain(23F)-1, Spain(6B)-2, Spain(9V)-3, and Spain(14)-5).

Antimicrob Agents Chemother, 2003 Nov, 47(11), 3605 - 9
First Streptococcus agalactiae isolates highly resistant to quinolones, with point mutations in gyrA and parC; Kawamura Y et al.; Three isolates of Streptococcus agalactiae highly resistant to multiple fluoroquinolones were isolated in Japan . Compared with susceptible strains of S . agalactiae, these quinolone-resistant strains had double point mutations within the quinolone resistance-determining regions of gyrA and parC; Ser-81 was changed to Leu (TCA --> TTA) in the amino acid sequence deduced from gyrA, and Ser-79 was changed to Phe (TCC --> TTC) in the amino acid sequence deduced from parC . Comparative sequence analysis revealed the possibility of gene transfer between S . agalactiae and another beta-hemolytic streptococcus, Streptococcus difficile.

Protein Sci, 2003 Nov, 12(11), 2613 - 21
Solution structure and function of an essential CMP kinase of Streptococcus pneumoniae; Yu L et al.; Streptococcus pneumoniae is a major human pathogen that causes high mortality and morbidity and has developed resistance to many antibiotics . We show that the gene product from SP1603, identified from S . pneumoniae TIGR4, is a CMP kinase that is essential for bacterial growth . It represents an attractive drug target for the development of a novel antibiotic to overcome the problems of drug resistance development for this organism . Here we describe the three-dimensional solution structure of the S . pneumoniae CMP kinase as determined by NMR spectroscopy . The structure consists of eight alpha-helices and two beta-sheets that fold into the classical core domain, the substrate-binding domain, and the LID domain . The three domains of the protein pack together to form a central cavity for substrate-binding and enzymatic catalysis . The S . pneumoniae CMP kinase resembles the fold of the Escherichia coli homolog . An insertion of one residue is observed at the beta-turn in the substrate-binding domain of the S . pneumoniae CMP kinase when compared with the E . coli homolog . Chemical shift perturbations caused by the binding of CMP, CDP, and ATP revealed that CMP or CDP binds to the junction between the core and substrate-binding domains, whereas ATP binds to the junction between the core and LID domains . From NMR relaxation studies, we determined that the loops in the LID domain are highly mobile . These mobile loops could aid in the closing/opening of the LID domain during enzyme catalysis.

Infect Immun, 2003 Nov, 71(11), 6676 - 9
The MicAB two-component signaling system is involved in virulence of Streptococcus pneumoniae; Kadioglu A et al.; In Streptococcus pneumoniae, the two-component signaling system MicAB was previously shown to contribute to repression of competence when oxygen is limited . In virulent strains expressing the serotype 2 and 6 capsule, mutation of the MicB kinase reduced the lag period of growth when cultures were switched from an aerobic to anaerobic atmosphere . After intranasal challenge of mice, the micB::km mutation decreased virulence, as shown by the absence of symptoms and by a lower level of recovery of CFU from lungs and blood . It is proposed that MicAB is involved in the adaptive response of the bacteria to changes in oxygen level during the course of infection.

Infect Immun, 2003 Nov, 71(11), 6344 - 53
Critical role of the complement system in group B streptococcus-induced tumor necrosis factor alpha release; Levy O et al.; Group B Streptococcus (GBS) is a major cause of newborn sepsis and meningitis and induces systemic release of tumor necrosis factor alpha (TNF-alpha), believed to play a role in morbidity and mortality . While previous studies have shown that GBS can induce TNF-alpha release from monocytes and macrophages, little is known about the potential modulating effect of plasma or serum on GBS-induced TNF-alpha release, and there are conflicting reports as to the host receptors involved . In a human whole-blood assay system, GBS type III COH-1 potently induced substantial monocyte TNF-alpha release in adult peripheral blood and, due to a higher concentration of monocytes, 10-fold-greater TNF-alpha release in newborn cord blood . Remarkably, GBS-induced TNF-alpha release from human monocytes was enhanced approximately 1000-fold by heat-labile serum components . Experiments employing C2-, C3-, or C7-depleted serum demonstrated that C3 activation via the alternative pathway is crucial for potent GBS-induced TNF-alpha release . Accordingly, whole blood from C3-deficient mice demonstrated significantly reduced GBS-induced TNF-alpha release . Preincubation with human serum enhanced the TNF-alpha-inducing activity of GBS in a C3- and factor B-dependent manner, implying deposition of complement components via the alternative pathway . GBS-induced TNF-alpha release was inhibited by monoclonal antibodies directed against each of the components of CR3 and CR4: the common integrin beta subunit CD18 and the alpha subunits CD11b (of CR3) and CD11c (of CR4) . Blood derived from CR3 (CD11b/CD18)-deficient mice demonstrated a markedly diminished TNF-alpha response to GBS . We conclude that the ability of plasma and serum to greatly amplify GBS-induced TNF-alpha release reflects the activity of the alternative complement pathway that deposits fragments on GBS and thereby enhances CR3- and CR4-mediated monocyte activation.

Infect Immun, 2003 Nov, 71(11), 6199 - 204
Phage lytic enzyme Cpl-1 as a novel antimicrobial for pneumococcal bacteremia; Loeffler JM et al.; Streptococcus pneumoniae is becoming increasingly antibiotic resistant worldwide, and thus new antimicrobials are badly needed . We report the use of Cpl-1, the lytic enzyme of a pneumococcal bacteriophage, as an intravenous therapy for pneumococcal bacteremia in a mouse model . A 2000- microg dose of Cpl-1 reduced pneumococcal titers from a median of log(10) 4.70 CFU/ml to undetectable levels (<log(10) 2.00 CFU/ml) within 15 min . This dose given 1 h after intravenous infection led to 100% survival at 48 h, compared to the 20% survival of buffer-treated controls . In advanced bacteremia, treatment with two doses at 5 and 10 h still resulted in significantly longer survival (P < 0.0001) and a hazard ratio of 0.29 (95% confidence interval, 0.04 to 0.35) . The enzyme is immunogenic, but the treatment efficacy was not significantly diminished after previous intravenous exposure of mice and hyperimmune rabbit serum did not neutralize the activity . Cpl-1 is also very effective as a topical nasal treatment against colonization by S . pneumoniae . In vitro, the enzyme is active against many serotypes of S . pneumoniae, independent of their penicillin resistance, and it is very specific for this species . Bacteriophage enzymes are unusual but extremely effective antimicrobials and represent a new weapon against infections with resistant bacteria.

Infect Immun, 2003 Nov, 71(11), 6192 - 8
Genetic basis for the structural difference between Streptococcus pneumoniae serotype 15B and 15C capsular polysaccharides; van Selm S et al.; In a search for the genetic basis for the structural difference between the related Streptococcus pneumoniae capsular serotypes 15B and 15C and for the reported reversible switching between these serotypes, the corresponding capsular polysaccharide synthesis (cps) loci were investigated by keeping in mind that at the structural level, the capsules differ only in O acetylation . The cps locus of a serotype 15B strain was identified, partially PCR amplified with primers based on the related serotype 14 sequence, and sequenced . Sequence analysis revealed, among other open reading frames, an intact open reading frame (designated cps15bM) whose product, at the protein level, exhibited characteristics of previously identified acetyltransferases . Genetic analysis of the corresponding region in a serotype15C strain indicated that the same gene was present but had a premature stop in translation . Closer analysis indicated that the serotype 15B gene contained a short tandem TA repeat consisting of eight TA units . In serotype 15C, this gene contained nine TA units that resulted in a frameshift and a truncated product . Genetic analysis of 17 serotype 15B and 15C clinical isolates revealed a perfect correlation between the serotype and the length of the short tandem repeat in the putative O-acetyltransferase gene . The number of TA repeating units varied between seven and nine in the various isolates . Together, the data strongly suggest that the structural difference between serotypes 15B and 15C is based on variation in the short tandem TA repeat in the O-acetyltransferase gene and that the transition between serotypes is due to slipped-strand mispairing with deletion or insertion of TA units in the cps15bM gene.

Infect Immun, 2003 Nov, 71(11), 6141 - 7
One of two human lactoferrin variants exhibits increased antibacterial and transcriptional activation activities and is associated with localized juvenile periodontitis; Velliyagounder K et al.; The iron-binding protein lactoferrin is a ubiquitous and abundant constituent of human exocrine secretions . Lactoferrin inhibits bacterial growth by sequestering essential iron and also exhibits non-iron-dependent antibacterial, antifungal, antiviral, antitumor, anti-inflammatory, and immunoregulatory activities . All of these non-iron-dependent activities are mediated by the highly charged N terminus of lactoferrin . In this study we characterized a Lys/Arg polymorphism at position 29 in the N-terminal region of human lactoferrin that results from a single nucleotide polymorphism in exon 1 of the human lactoferrin gene . We expressed cDNAs encoding both lactoferrin variants in insect cells and purified the two proteins by ion exchange chromatography . The two lactoferrin variants exhibited nearly identical iron-binding and iron-releasing activities and equivalent bactericidal activities against a strain of the gram-negative bacterium Actinobacillus actinomycetemcomitans . When tested against the gram-positive species Streptococcus mutans and Streptococcus mitis, however, lactoferrin containing Lys at position 29 exhibited significantly greater bactericidal activity than did lactoferrin containing Arg . In addition, the Lys-containing lactoferrin stimulated bovine tracheal epithelial cells to synthesize much higher levels of tracheal antimicrobial peptide mRNA than did the Arg-containing variant . A genotyping assay that distinguished between the two alleles based on a polymorphic EarI restriction site showed that the Lys and Arg alleles had frequencies of 24% and 76%, respectively, among 17 healthy human subjects, and 72% and 28%, respectively, among nine patients with localized juvenile periodontitis . Our findings suggest that these two lactoferrin variants are functionally different and that these differences may contribute to the pathogenesis of localized juvenile periodontitis.

Cytokine, 2003 Nov 21, 24(4), 143 - 9
Balance of tumor necrosis factor alpha and interleukin-10 in a buccal infection in a streptozotocin-induced diabetic rat model; Furudoi S et al.; This study evaluates the local levels of proinflammatory cytokine, tumor necrosis factor alpha (TNF-alpha), and anti-inflammatory cytokine, interleukin-10 (IL-10), in an experimental buccal abscess of a diabetic rat model . We prepared a buccal cavity induced by injection of carrageenin in a diabetic rat (blood glucose, 460.6 +/- 54.7 mg/dl, mean +/- SE) induced by streptozotocin (STZ) . The buccal abscess was formed by the direct inoculation of Streptococcus pyogenes S-8 (2 x 10(7) cfu) into the buccal cavity at day 5 after carrageenin injection . Cytokine levels in the exudate of the buccal abscess were measured by enzyme-linked immunosorbent assay for 48 h after infection . Bacterial counts, weighing of exudate, and histological analysis were also performed . The mean TNF-alpha levels in the buccal abscess exudate of the diabetic group, which were generally higher than those of the control group, tended to increase over time until 48 h after infection, while the TNF-alpha levels in the control group peaked at 24 h after infection and then decreased . The IL-10 levels in the diabetic group remained almost unchanged until 48 h after infection, while the IL-10 levels in the control group were significantly higher than in the diabetic group at 12-24 h after infection . The mean ratio of TNF-alpha to IL-10 levels was 1.17-1.67 in the diabetic group, which was higher than the 0.26-0.69 of the control group . The bacterial counts in the buccal abscess and the weight of exudate were significantly higher in the diabetic group compared to the control group at 36-48 h . Histological findings showed that inflammatory cell infiltration was remarkable in the diabetic group compared to that of the control group . These results suggest that the elevated proinflammatory TNF-alpha levels and decreased anti-inflammatory IL-10 levels, which are produced at local infection sites, may at least in part be related to the severity of inflammation in this rat model with diabetes induced by STZ.

Can Respir J, 2003 Oct, 10(7), 368 - 74
A comparison of bacteremic pneumococcal pneumonia with nonbacteremic community-acquired pneumonia of any etiology--results from a Canadian multicentre study; Marrie TJ et al.; BACKGROUND: Bacteremic pneumococcal pneumonia has not been the subject of a multicentre Canadian Study . OBJECTIVES: To compare bacteremic community-acquired Streptococcus pneumoniae pneumonia with nonbacteremic community-acquired pneumonia of any etiology . METHODS: A prospective cohort study was conducted at 15 centres in eight Canadian provinces from January 1996 to January 1998 . RESULTS: Fifty-six of the 450 patients (12.4%) had one or more blood cultures positive for S pneumoniae . Compared with the 394 blood culture-negative patients, the bacteremic patients were younger (55.6 years versus 63.4 years; P=0.002) . At presentation, bacteremic patients had a higher mean oral temperature (38.1+/-1.2 degrees C versus 37.7+/-1.2 degrees C; P=0.026), a higher pulse rate (108.4+/-22.1 beats/min versus 102.1+/-20.6 beats/min; P=0.033), a lower diastolic blood pressure reading (66.8+/-12.7 mmHg versus 73.8+/-15.8 mmHg; P=0.001) and a higher percentage of white blood cells that were band forms (22.1% versus 14.2%; P=0.0007) . The time from onset of symptoms until admission to hospital was shorter among the bacteremic patients (4.6+/-3.7 days versus 7.0+/-13.9 days; P=0.005) . Three capsular polysaccharide types accounted for 53.4% of the isolates: type 14, 29.2%; type 4, 12.1%; and type 22 F, 12.1% . Two of 44 isolates were resistant to penicillin . CONCLUSIONS: While some differences in patient characteristics and presentation occur when patients with bacteremic pneumococcal pneumonia are compared with nonbacteremic patients with community-acquired pneumonia, there is considerable overlap, and clinical presentation does not allow one to distinguish the bacteremic patients from the nonbacteremic patients.

Caries Res, 2003 Nov-Dec, 37(6), 416 - 24
Ion release from copper phosphate cement and influence on Streptococcus mutans growth in vitro: a comparative study; Foley J et al.; The aim of this study was to compare the effects of a black copper cement (BCC), an established restorative material (a conventional glass ionomer cement) and two temporary restorative materials (a zinc phosphate and a zinc polycarboxylate cement) on the growth of Streptococcus mutans in vitro, and to correlate bacterial growth with ion release from each material . Test specimens were eluted in either 0.1 M lactic acid, pH 4, or 0.1 M sodium chloride, pH 7 . At 2 days, 7 days, 28 days and 6 months, eluates were inoculated with S . mutans and bacterial growth was recorded . Metal ion (Cu(2+), Zn(2+ )and Mg(2+)) and fluoride release were measured . At most immersion times, the different materials had a statistically significant inhibitory effect on bacterial growth compared to the respective control, at both pH levels . The inhibitory effect decreased with time and in most cases was associated with high levels of ion release at the beginning of the experimental period, followed by significantly lower levels . For BCC, there were statistically significant relationships between the median rates of growth of S . mutans in the presence of BCC eluates and the median values for release of copper and zinc, although not magnesium . Of the different materials, BCC demonstrated greatest antibacterial activity .

South Med J, 2003 Oct, 96(10), 960 - 7
Laboratory survey of antibiotic nonsusceptibility among Streptococcus pneumoniae isolates in South Carolina, 1998 versus 2000; Dauner DG et al.; BACKGROUND: In 1998, the South Carolina Department of Health and Environmental Control surveyed clinical microbiology laboratories statewide to determine the prevalence of antibiotic nonsusceptibility among isolates of Streptococcus pneumoniae . A follow-up study was conducted in 2001 . METHODS: A cross-sectional study was conducted to estimate the prevalence of penicillin nonsusceptibility (PCN-N), extended-spectrum cephalosporin nonsusceptibility (ESC-N), and levofloxacin nonsusceptibility (LEV-N) in South Carolina . A standardized questionnaire was mailed to 89 laboratories . RESULTS: The prevalence of penicillin intermediate resistance increased from 1998 (17.6%) to 2000 (20.9%, chi2 P = 0.008) . Furthermore, the prevalence of PCN-N increased from 1998 (34.5%) to 2000 (38.4%, chi2 P = 0.01) . The prevalence of ECN-N decreased from 1998 (19.1%) to 2000 (17.7%), but the difference was not significant (chi2 P = 0.25) . CONCLUSION: The laboratory survey was a low-cost method of estimating the change in prevalence of antibiotic nonsusceptibility, and it emphasizes regional surveillance because the prevalence of antibiotic nonsusceptibility varied geographically.

Geriatrics, 2003 Oct, 58(10), 20 - 2, 25
Preventing pneumococcal disease . ACIP recommends pneumococcal polysaccharide vaccine for all adults age > or = 65; Whitney CG; Streptococcus pneumoniae remains the most common cause of community-acquired pneumonia and bacterial meningitis in older adults . Current recommendations from CDC's Advisory Committee on Immunization Practices suggest providing pneumococcal polysaccharide vaccine to all adults age 65 and older and to persons age 2 to 64 with chronic illnesses that place them at higher risk for pneumococcal disease . In addition, vaccination status should be assessed for residents of nursing homes and long-term care facilities on admission and vaccine administered as needed . Although the polysaccharide vaccine is safe, effective against invasive disease, and cost-effective, many older adults have not yet received the vaccine . Use of standing orders is encouraged as a way to improve vaccine delivery . Research into new vaccines to prevent pneumococcal disease in older adults is ongoing.

J Am Vet Med Assoc, 1999 Dec 1, 215(11), 1666 - 70
Empyema of the guttural pouch (auditory tube diverticulum) in horses: 91 cases (1977-1997); Judy CE et al.; OBJECTIVE: To identify features of guttural pouch (auditory tube diverticulum) empyema in horses and compare findings of uncomplicated guttural pouch empyema with guttural pouch empyema complicated by chondroids . DESIGN: Retrospective study . ANIMALS: 91 horses with guttural pouch empyema . PROCEDURE: Medical records of horses with guttural pouch empyema were reviewed . RESULTS: The most common owner complaint and abnormal finding was persistent nasal discharge . Chondroids were detected in 21% (19/91) of affected horses . Streptococcus equi was isolated from the guttural pouch in 14 of 44 horses; for Streptococcus spp, in vitro resistance to sulfadimethoxine and trimethoprim-sulfamethoxazole was detected . Retropharyngeal swelling and pharyngeal narrowing were significantly more prevalent in horses with chondroids, compared with horses with uncomplicated empyema . Ninety-three percent of affected horses were discharged from the hospital; at time of discharge, 66% had complete resolution of disease, 19% had improvement without resolution, and 15% did not have improvement . CONCLUSIONS AND CLINICAL RELEVANCE: Horses with persistent nasal discharge should be examined endoscopically for guttural pouch empyema . Treatment with lavage offers a good prognosis for resolution of uncomplicated guttural pouch empyema . Aggressive treatment with lavage and endoscopic snare removal of chondroids offers a good prognosis and may make surgical intervention unnecessary.

Schweiz Monatsschr Zahnmed, 2003, 113(9), 985 - 96
{Effect of mouthwashing with tea tree oil on plaque and inflammation}; Saxer UP et al.; The tea tree oil (melaleuca alternifolia) has antiseptic, fungicide and bactericide effects . The efficiency against oral bacteria was also evident . Xylitol is known for counterattacking the cariogenic effect caused by the streptococcus mutans . Less plaque was developed during the time of the study.

Pediatr Infect Dis J, 2003 Aug, 22(8 Suppl), S139 - 48
Amoxicillin/clavulanate for infections in infants and children: past, present and future; Klein JO; Chemical synthesis of the penicillin nucleus in the 1950s made introduction of a broad array of new and important antimicrobials, including ampicillin and amoxicillin, possible . Ampicillin was introduced in 1962 in oral and parenteral forms as the first of the semisynthetic penicillins to provide increased activity against Gram-negative bacteria . Amoxicillin replaced oral ampicillin beginning in 1974 because amoxicillin resulted in higher and more prolonged serum concentrations than did equivalent doses of ampicillin . Amoxicillin/clavulanate (Augmentin) was introduced in the United States in 1984 to enhance the activity of amoxicillin by addition of the beta-lactamase inhibitor, clavulanic acid . During the past 20 years, amoxicillin/clavulanate has proven effective for a variety of pediatric infectious diseases, particularly acute otitis media (AOM) . In 2001, a new pediatric formulation, high dose amoxicillin/clavulanate (Augmentin ES-600) was approved for use in the United States . The high dose preparation addressed the needs of pediatricians by providing greater amounts of amoxicillin while maintaining the same daily dose of clavulanic acid as the regular strength formulation . Doubling the dose of amoxicillin for management of recurrent and persistent AOM was recommended in 1999 by the Centers for Disease Control and Prevention because of concern about the increased incidence of nonsusceptible strains of Streptococcus pneumoniae . The original formulation combined amoxicillin/clavulanate in a 4:1 ratio and was followed by a 7:1 ratio formulation . The high dose formulation (600 mg of amoxicillin per 5 ml) provides a 14:1 ratio of amoxicillin to clavulanate . Although management of AOM will likely undergo changes in the coming years, amoxicillin is expected to remain first line therapy for AOM . For children who fail initial therapy with amoxicillin, high dose amoxicillin/clavulanate, an oral cephalosporin or parenteral ceftriaxone is recommended.

J Antimicrob Chemother, 2003 Nov, 52(5), 826 - 36 Epub 2003 Oct 16.
Oral pharmacokinetically enhanced co-amoxiclav 2000/125 mg, twice daily, compared with co-amoxiclav 875/125 mg, three times daily, in the treatment of community-acquired pneumonia in European adults; Garau J et al.; OBJECTIVES: Pharmacokinetically enhanced co-amoxiclav 2000/125 mg was designed to achieve high serum concentrations of amoxicillin over the 12 h dosing interval to eradicate Streptococcus pneumoniae with amoxicillin MICs of at least 4 mg/L . METHODS: This randomized, double-blind, double-dummy, multicentre study compared the efficacy and safety of oral co-amoxiclav 2000/125 mg twice daily versus co-amoxiclav 875/125 mg three times daily, for 7 or 10 days, in the treatment of community-acquired pneumonia (CAP) . RESULTS: The per-protocol (PP) population at follow-up (Days 18-39) comprised 114 patients receiving co-amoxiclav 2000/125 mg and 116 receiving co-amoxiclav 875/125 mg . Clinical success at follow-up (primary efficacy endpoint) in the clinical PP population was 94.7% (108/114) for co-amoxiclav 2000/125 mg versus 88.8% (103/116) for co-amoxiclav 875/125 mg {treatment difference (TD) = 5.9%, 95% CI: 1.1, 13.0} . Bacteriological success in the bacteriology PP population at follow-up was 85.0% (17/20) for co-amoxiclav 2000/125 mg versus 77.3% (17/22) for co-amoxiclav 875/125 mg (TD = 7.7%, 95% CI: 15.8, 31.2) . Penicillin-resistant S . pneumoniae (PRSP) were isolated in three patients (including two with bacteraemia) in the co-amoxiclav 2000/125 mg group (amoxicillin MICs 8 mg/L, penicillin MICs 4 mg/L) and one in the comparator group; all were clinical and bacteriological successes . Co-amoxiclav 2000/125 mg and co-amoxiclav 875/125 mg were associated with adverse events leading to withdrawal in 6.3% and 6.2% of patients, respectively . CONCLUSIONS: Co-amoxiclav 2000/125 mg twice daily was at least as effective clinically as co-amoxiclav 875/125 mg three times daily in the treatment of CAP . Although few patients in this study had PRSP infection, 3/3 were successfully treated with co-amoxiclav 2000/125 mg.

Int J Infect Dis, 2003 Sep, 7(3), 190 - 7
Penicillin susceptibility and molecular characteristics of clinical isolates of Streptococcus pneumoniae at the University of Malaya Medical Center, Kuala Lumpur, Malaysia; Desa MN et al.; OBJECTIVE: To determine the prevalence of penicillin resistance and molecular characteristics of pneumococcal isolates at the University of Malaya Medical Center . METHODS: From March 1999 to July 2000, 100 clinical isolates of Streptococcus pneumoniae were obtained from 93 patients of various ages and from various body sites . The minimum inhibitory concentrations (MICs) for penicillin and ceftriaxone were determined by E test, and results were interpreted according to guidelines recommended by the National Committee for Clinical Laboratory Standards (NCCLS) . Fifty isolates were further serotyped, and analyzed by pulsed-field gel electrophoresis (PFGE) and polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) of the penicillin-binding protein (pbp) 2b and 2x genes . RESULTS: The majority of the isolates were from respiratory sites . Thirty-one isolates showed decreased susceptibility to penicillin (PRSP), and many of these also showed decreased susceptibility to ceftriaxone . Twelve serogroup/types (SGTs) were present, with 19F being the most common . PFGE analysis identified two dominant profiles, consisting mainly of PRSPs that had common serotypes (19F) and pbp gene patterns within their respective groups, although PCR-RFLP analysis showed different patterns of pbp genes among the PRSPs as compared to penicillin-susceptible strains, which had a uniform pattern . CONCLUSION: PRSPs were genetically related as shown by PFGE and serotype . The consistency of pbp gene patterns, observed among many of the PRSPs within their respective PFGE profiles, supported their relatedness as established by PFGE.

Int J Infect Dis, 2003 Sep, 7(3), 183 - 9
Pediatric invasive pneumococcal disease in a teaching hospital in Bangkok; Sirinavin S et al.; BACKGROUND: Increased problems with drug-resistant Streptococcus pneumoniae (SP) and the dearth of epidemiologic and clinical information on invasive pneumococcal disease in children in Asia formed the basis for this study . METHODS: A periodic retrospective review of the records of 0-15-year-old patients was conducted at a teaching hospital in Bangkok, during 1971-2000 . RESULTS: Infections with penicillin-non-susceptible SP (PNSSP) strains rapidly increased after they first appeared in 1988, and they accounted for 71% (29/41) of the total cases during 1996-2000 . Of 137 patients, 74% were <60 months old, and 66% had an underlying condition . Infections included: bacteremia without focus 51; pneumonia 38; meningitis 35; peritonitis 13; and bone/joint infection 2 . Two patients had two foci of infection . Eight of 10 episodes in patients with AIDS were bacteremic pneumonia . Median ages (range) in months for patients with and without an underlying condition were 24 (1-174) and 10 (0-160); and for the patients without an underlying condition they were: pneumonia 23 (4-156); bacteremia without focus 12 (0-160); and meningitis 7 (2-156) . Case-fatality rates were 18% and 2% for patients with and without an underlying condition . The study also examined factors associated with PNSSP infection and death . During 1991-2000, 74% (43/58) of the total cases occurred from November to April, which are dry months . CONCLUSIONS: This study population contained a high proportion with both an underlying condition and infection with PNSSP, and a moderately low proportion with bacteremia without focus . The disease was two to three times more common in dry months than in rainy months.

Infection, 2003 Aug, 31(4), 251 - 3
Streptococcus pneumoniae as an uncommon cause of superinfected pancreatic pseudocysts; Gubler C et al.; We report a patient with pancreatic pseudocysts that were superinfected with Streptococcus pneumoniae . The literature on the prevalence of superinfection of pancreatic tissue by S . pneumoniae, as well as on its prophylaxis and treatment, is reviewed . In addition, a possible pathophysiologic pathway is discussed.

Infection, 2003 Aug, 31(4), 244 - 6
Maternal carriage and antimicrobial resistance profile of group B Streptococcus; Arisoy AS et al.; BACKGROUND: The aim of this study was to determine the prevalence of group B Streptococcus (GBS) colonization and to evaluate the antimicrobial resistance profile in women in the third trimester of pregnancy . MATERIALS AND METHODS: A total of 310 pregnant women, referred in weeks 35 to 37 of gestation, were screened for GBS colonization during a 10-month period . Samples were collected from the vagina and the rectum . RESULTS: The colonization rate was 10.6% and 22 women (66.7%) had both positive vaginal and rectal cultures . Rates of GBS colonization were significantly lower in patients aged 24 years or older and in those with a third or later pregnancy . None of the isolates were resistant to penicillin and ampicillin, whereas 21.2% and 9.1% showed resistance to erythromycin and clindamycin, respectively . CONCLUSION: Screening and antimicrobial susceptibility testing of GBS during pregnancy are important to guide appropriate therapy.

Avian Dis, 2003 Jul-Sep, 47(3), 559 - 65
Association of Streptococcus gallolyticus strains of high and low virulence with the intestinal tract of pigeons; Kimpe A et al.; We investigated the ability of a high virulence (STR 357) and a low virulence (STR 598) strain of Streptococcus gallolyticus to attach to the intestinal tract of pigeons . For that purpose, first of all, two groups of six pigeons were anesthetized and ligatures were placed at the beginning of duodenum, jejunum, ileum, and colon . The obtained intestinal loops of the birds of the first and second group were injected with S . gallolyticus strains STR 357 and STR 598, respectively . At 15, 30, and 60 min postinoculation, two pigeons of each group were euthanatized and the various intestinal loops were sampled for histologic, immunohistochemical, and electron microscopic examination . Both the high and low virulence strains were able to adhere to the intestinal mucosa . Indeed, all samples dearly showed numerous coccal-shaped bacteria that stained positively with S . gallolyticus antiserum and were lining up against the intestinal epithelium . Likewise, on electron microscopic examination, cocci were seen in the mucus covering the intestinal epithelium . Second, the association of S . gallyticus strains of differing virulence with the intestinal tissue was determined quantitatively . Experiments were performed as described above . The number of S . gallolyticus bacteria that adhered to the intestinal epithelium was determined by plating out 10-fold serial dilutions of the segments . No significant differences in the number of adhered bacteria were found between the strains of high and low virulence.

J Reprod Med, 2003 Sep, 48(9), 697 - 702
Cell wall proteins of group B Streptococcus and low incidence of neonatal disease in southern Israel; Marchaim D et al.; OBJECTIVE: To determine the maternal group B Streptococcus (GBS) prevalence of carriage and serotype distribution and the neonatal disease incidence to formulate a policy for treatment and prevention regarding GBS diseases in southern Israel . STUDY DESIGN: A prospective study was conducted between January and October 2000 . Cultures were obtained from 681 healthy, pregnant women and processed as recommended . Samples were cultured on blood-agar plates with and without added gentamicin . GBS was identified by beta-hemolysis and a positive CAMP test and confirmed by agglutination with specific antiserum . Serotyping was done by the Lancefield precipitin method using monospecific antisera to polysaccharides Ia, Ib and II-VIII and surface proteins C, R and X . RESULTS: Carriage prevalence of 12.3% and neonatal disease incidence of 0.095/1,000 live births were documented . Surface proteins C and R were found in 85.7% of positive cases . Serotypes Ia (17.8%), Ib (10.7%), II (27.4%), III (20.2%) and V (14.3%) were distributed as previously reported from developed countries . CONCLUSION: Developing a pentavalent vaccine based on serotypes Ia, Ib, II, III and V in conjugation to a GBS cell wall protein transporter, such as C or R, has theoretical advantages in the southern Israeli population over vaccines that use foreign proteins.

Dtsch Tierarztl Wochenschr, 2003 Sep, 110(9), 378 - 81
{Occurrence and diagnostic relevance of virulence-associated factors in Streptococcus suis}; Baums CG et al.; Streptococcus suis (Sc . suis) can cause very different clinical entities . In contrast to Sc . suis-associated pneumonia, the induction of meningitis, septicemia, and polyarthritis by certain Sc . suis strains requires the expression of virulence factors that contribute to the invasiveness of the pathogen . In the presented study, we examined the occurrence of known virulence-associated factors in Sc . suis isolates from samples sent to the Institute of Microbiology, School of Veterinary Medicine Hannover, in order to evaluate their significance as potential virulence factors in different disease complexes in Northern Germany . The results show that (i) MRP + EF + serotype 2 and MRP* EF-serotype 9 strains are statistically significant associated with the disease complex meningitis/septicemia/arthritis and, thus, have to be considered invasive strains, (ii) serotyping alone is not sufficient for identification of virulent strains, (iii) there is a remarkable heterogeneity among pneumonia-associated Sc . suis strains and (iv) activity of haemolysin or suilysin appears to be not appropriate as virulence marker . Finally, it has to be noted that at present only half of the Sc . suis isolates from pigs with meningitis/septicemia/poyarthritis can be characterised by the detection of virulence-associated factors . Thus, the identification and characterisation of additional, serotype independent virulence factors of Sc . suis is a very important issue in future studies.

Rev Prat, 2003 Sep 15, 53(13), 1451 - 7
{Treatment and prevention of pneumococcal pneumonia}; Leophonte P et al.; Streptococcus pneumoniae is the most commonly identified pathogen in patients with community-acquired pneumonia . 40% of isolated strains in France are of decreased sensibility to penicillin, two third being multiresistant to antibiotics . However, high doses of some beta-lactams are effective in vivo against the majority of circulating strains (MIC > 2 mg/L) . For this reason according to French guidelines amoxicillin (3 g/day) is the first line recommended treatment . Telithromycin is an alternative, or ceftriaxone (1 g/day) in more severe cases . If the level of resistance increases (MIC > 4 mg/L) guidelines would be revisited . Effectiveness of pneumococcal vaccination has been confirmed in cases of bacteriemic pneumococcal pneumonia (elderly patients included) . Vaccine is recommended among persons with comorbiditie(s) and 65 years old population.

Rev Prat, 2003 Sep 15, 53(13), 1434 - 41
{Community acquired pneumonia in the elderly}; Gaillat J; Pneumonia, more frequent in the elderly, results in higher morbidity and mortality, and is a frequent cause of hospitalisation . Although the incidence of pneumonia increases with age, mainly after 70-75 years, life in institution, comorbid medical illness (heart disease, chronic obstructive pulmonary disease, dementia), malnutrition and defence impairments are independent risk factors . Older patients with pneumonia complain of significantly fewer symptoms than younger patients . Streptococcus pneumonia is the most common cause of pneumonia, atypical pathogen are rare . There is a shift toward gram-negative bacteria and opportunistic flora with increasing age and severity of concomitant medical illness . Anaerobic bacteria are frequent in aspiration pneumonia . To hospitalize or not is the first decision to take, based on clinical criteria and risks factors . Use of the guidelines for empirical treatment of pneumonia is recommended . Old patients often recover slowly . Pneumococcal and influenza vaccinations are effective and warranted.

Rev Prat, 2003 Sep 15, 53(13), 1417 - 25
{Diagnosis of community acquired pneumonia in adults}; Benhamou D et al.; In contrast with acute bronchitis, which is benign and very frequent, community acute pneumonia has to be considered as a serious illness with a mortality rate that can reach 10-15% in inpatients . In adult, pneumonia is usually due to bacteria and antibiotherapy is always required . Clinical diagnosis is based on presumption signs: fever, tachycardia, tachypnea, thoracic pain, localised rales and a global severity impression . A chest X-ray is required . The pathogens involved are usually Streptococcus pneumoniae or atypical organisms . In inpatients (severe pneumonia or presence of risk factors), other pathogens such as gram negative bacilli or anaerobes are possible . The accurate diagnosis is based on invasive methods, which are not justified in outpatients but indicated in severe pneumonia.

Clin Infect Dis, 2003 Nov 1, 37(9), e132 - 5 Epub 2003 Oct 03.
Case report and literature review of late-onset group B streptococcal disease manifesting as necrotizing fasciitis in preterm infants: is this a new syndrome?
Lang ME, Vaudry W, Robinson JL.
We describe a 5-month-old preterm female infant who presented with necrotizing fasciitis involving the face and neck caused by group B streptococcus (GBS) . Because of the extent and anatomic location of the necrosis, surgical debridement was delayed for 16 days, but the infant survived . Review of the literature demonstrated that 3 of the 10 previously reported cases of necrotizing fasciitis caused by GBS involved preterm infants and that 2 of these cases also involved the head and neck.

Clin Infect Dis, 2003 Nov 1, 37(9), 1261 - 4 Epub 2003 Sep 30.
Serum concentrations of pneumococcal anticapsular antibodies in children with pneumonia associated with Streptococcus pneumonia infection; Esposito S et al.; The levels of specific IgG antibody to pneumococcal capsular polysaccharides were investigated in 182 children, aged 2-5 years, who were hospitalized for community-acquired pneumonia, including 55 (30.2%) with evidence of acute pneumococcal infection . Results show that children with concentrations of specific IgG antibody that would protect against invasive disease do not seem to be protected against pneumonia associated with pneumococcal infection.

Clin Infect Dis, 2003 Nov 1, 37(9), 1210 - 5 Epub 2003 Oct 02.
Gatifloxacin, gemifloxacin, and moxifloxacin: the role of 3 newer fluoroquinolones; Saravolatz LD et al.; Gatifloxacin, gemifloxacin, and moxifloxacin are the newest fluoroquinolones and show excellent in vitro activity against a wide variety of respiratory tract pathogens, many gram-negative aerobic organisms, and Bacteroides fragilis . These agents may be administered as oral and/or intravenous formulations with excellent bioavailability . The pharmacodynamics of these 3 new fluoroquinolones is more favorable than that of levofloxacin or ciprofloxacin for Streptococcus pneumoniae . All 3 agents are approved for the treatment of acute exacerbation of chronic bronchitis and community-acquired pneumonia . In addition, gatifloxacin and moxifloxacin are approved for the treatment of sinusitis . The toxicity of these 3 agents appears to be similar to that of the other fluoroquinolones in terms of gastrointestinal and central nervous system disturbances . All 3 agents have a low risk of phototoxicity, but gemifloxacin is associated with an increased risk of skin rash that is not a photoreaction . These agents can be useful for treatment of bacterial respiratory tract infections in patients who are allergic to beta-lactams, but caution must be exercised to avoid the potential for selection of widespread resistance, which may occur with indiscriminate use.

Clin Infect Dis, 2003 Nov 1, 37(9), 1189 - 93 Epub 2003 Oct 01.
Group A streptococcal infections in Sweden: a comparative study of invasive and noninvasive infections and analysis of dominant T28 emm28 isolates; Eriksson BK et al.; Surveillance of group A streptococcus (GAS) infections in Sweden during 1996-1997 indicated that T28 isolates were dominant, whereas T1M1 infections were uncommon . Circulating T28 isolates were nearly all emm28, MLST52, and these clones had also been prevalent 10 years earlier . Isolates from invasive and noninvasive infections were of similar types and prevalences . The average national incidence of invasive episodes was 2.9/100,000 population but varied between 0 and 8.3/100,000 population in different counties . It increased markedly with age, reaching 22.9 episodes/100,000 among people aged > or =90 years . The incidence of puerperal sepsis was higher than expected (22.4/100,000 of those at risk), with 1 death . Overall mortality was 16% and was associated with preexisting chronic disease (P=.002) . Streptococcal toxic shock syndrome (STSS) developed in approximately 15% of patients with invasive episodes, with a mortality rate of 45% . The use of nonsteroidal anti-inflammatory drugs was not found to be associated with the development of STSS.

Vet Res, 2003 Sep-Oct, 34(5), 521 - 64
Severity of E . coli mastitis is mainly determined by cow factors; Burvenich C et al.; Intramammary infections of dairy cows with Gram-positive bacteria such as Staphylococcus aureus (major cause of mastitis) have received a lot of attention because of their major economic impact on the dairy farm through production losses induced by an increase in somatic cell count . Management strategies, including greater awareness for efficient milking and hygienic measures, have limited the spread of Gram-positive bacteria and resulted in a significant decrease of proportion of S . aureus isolates and subclinical mastitis worldwide . Other organisms such as coliform subspecies and Streptococcus uberis, both environmental bacteria that cause clinical mastitis, have received less attention . Escherichia coli causes inflammation of the mammary gland in dairy cows around parturition and during early lactation with striking local and sometimes severe systemic clinical symptoms . This disease affects many high producing cows in dairy herds and may cause several cases of death per year in the most severe cases . It is well known that bacterial, cow and environmental factors are interdependent and influence mastitis susceptibility . Many studies, executed during the last decade, indicate that the severity of E . coli mastitis is mainly determined by cow factors rather than by E . coli pathogenicity . During E . coli mastitis, the host defense status is a cardinal factor determining the outcome of the disease . Today, we know that the neutrophil is a key factor in the cows' defense against intramammary infection with E . coli . Effective elimination of the pathogen by neutrophils is important for the resolution of infection and the outcome of E . coli mastitis . This review is a compilation of some major findings over the last 15 years concerning mainly host factors that modulate and influence neutrophil function and the mammary inflammatory reaction . The individual chapters address: virulence factors of E . coli strains, how neutrophils kill E . coli, connection between endotoxins, tumor necrosis factor-alpha and nitric oxide, severity classification of E . coli mastitis, lifespan of neutrophils, host factors that influence severity, tissue damage and production loss.

Infection, 2003 Oct, 31(5), 308 - 17
A pooled analysis of telithromycin in the treatment of community-acquired respiratory tract infections in adults; Carbon C; BACKGROUND: Thirteen multinational, Phase III studies were conducted to establish the efficacy of telithromycin 800 mg once daily in the treatment of community-acquired respiratory tract infections (RTIs) . PATIENTS AND METHODS: Data were analyzed from 4,743 adult patients participating across four indications: community-acquired pneumonia (CAP) of mild to moderate severity, acute exacerbations of chronic bronchitis (AECB), acute maxillary sinusitis (AMS) and tonsillitis/pharyngitis . RESULTS: Treatment with telithromycin for either 5 days (AECB, AMS and tonsillitis/pharyngitis) or 7-10 days (CAP and AMS) provided high rates of clinical and bacteriologic cure (5-day, 87.0% and 86.0%, respectively; 7 to 10-days, 90.3% and 90.5%, respectively) that were equivalent to those of a 10-day course of comparator antibacterials (86.5% and 86.5%, respectively) . The clinical efficacy of telithromycin extended to high-risk CAP and AECB patients and to all key respiratory pathogens, including Streptococcus pneumoniae strains resistant to penicillin or erythromycin and atypical/intracellular pathogens . Telithromycin was generally well-tolerated across patient groups . CONCLUSION: These findings support the use of telithromycin as an effective therapy for the treatment of community-acquired RTIs.

J Dent, 2003 Nov, 31(8), 543 - 8
Changes in enamel surface roughness and adhesion of Streptococcus mutans to enamel after vital bleaching; Hosoya N et al.; OBJECTIVES: The purpose of this in vitro study was to observe the influence of vital bleaching on changes to the enamel surface and adhesion of Streptococcus mutans to tooth enamel . METHODS: The coronal part of each of 70 extracted third molars was cut in half, with either the buccal or lingual half used for experiments or controls . Experimental halves were assigned to the following conditions: (A) enamel was bleached 1, 3 or 5 times using a bleaching material with or without etching; or (B) etched condition without bleaching . All control samples were kept intact in physiological saline solution . Surface roughness (Ra; roughness center-line average: microm) of enamel was measured for 35 pairs of specimens . TS broth culture medium containing 3% glucose was inoculated with S . mutans and cultured for 72 h before adding the other 35 pairs of specimens . Under scanning electron microscopy, the number of S . mutans colonies was counted and statistically analysed . RESULTS: Compared to controls, bleached enamel displayed increased colonies of S . mutans . Repeated bleaching further increased bacterial adhesion and maximal colonies counts were found under conditions of five bleaching treatments plus etching (p</=0.01) . Compared to controls, roughness increased after etching . However, no linear correlation was found between number of S . mutans colonies and roughness . CONCLUSION: We conclude that both surface roughness and adhesion of S . mutans to the enamel surface increase after bleaching.

Braz J Infect Dis, 2003 Oct, 7(5), 297 - 300
Detection of Group A beta-hemolytic Streptococcus employing three different detection methods: culture, rapid antigen detecting test, and molecular assay; Santos O et al.; In order to study the prevalence of Group A beta-hemolytic Streptococcus (GABHS) pharyngotonsillitis in our pediatric population and to compare different sampling methods of GABHS detection, oropharyngeal swabs from 50 children with acute pharyngotonsillitis, between 1 and 12 years old, were used simultaneously for culture, molecular assay and rapid GABHS antigen detection tests . All children were clinically examined at the Division of Pediatric Otorhinolaryngology of the Federal University of Sao Paulo . Diagnostic criteria were based on signs and symptoms, including sore throat, fever and oropharyngeal purulent secretion . Children that had been treated with antibiotics were excluded . Overall, combining the three methods, the prevalence of GABHS was 34% . GABHS was diagnosed in 30% of the bacterial cultures, in 25% of the samples tested with the molecular nucleic acid hybridization method and in 26% of the cases tested with the rapid antigen detection test . There was no significant difference between these three methods.

J Infect Dis, 2003 Oct 15, 188(8), 1132 - 7 Epub 2003 Oct 07.
Molecular characterization of serotype III group B-streptococcus isolates causing neonatal meningitis; Bidet P et al.; We studied a collection of 110 serotype III group B streptococcus (GBS) isolates causing neonatal meningitis, by means of both pulsed-field gel electrophoresis (PFGE) with SmaI and Southern hybridization with probes for genes potentially associated with virulence (neuA, cpsA, scpB, and hylB and, for mobile genetic elements {MGEs}, GBSi1 and IS1548), in comparison with 44 serotype III GBS isolates colonizing healthy neonates . Using polymerase chain reaction, we assessed both the insertion of MGEs downstream of the scpB gene and the insertion of IS1548 within the hylB gene . PFGE clustered the isolates into 3 main groups . One PFGE group accounted for 80% of typeable cerebrospinal fluid (CSF) isolates, versus 24% of colonization isolates (P=1.8 x 10-9) . GBSi1 was found in 67% of CSF isolates and in only 23% of colonization isolates (P=5.3 x 10-7) . A 15-kbp SmaI restriction-DNA fragment bearing the neuA gene was significantly associated with CSF isolates (P=1.1 x 10-11).

J Infect Dis, 2003 Oct 15, 188(8), 1119 - 31 Epub 2003 Oct 10.
Streptococcus pneumoniae-associated human macrophage apoptosis after bacterial internalization via complement and Fcgamma receptors correlates with intracellular bacterial load; Ali F et al.; Opsonization enhances Streptococcus pneumoniae-induced human monocyte-derived macrophage (MDM) apoptosis . Both depletion of complement and immunoglobulin from opsonizing serum and blockade of the macrophages CR1, CR3, FcgammaRII, and FcgammaRIII partially decreased MDM apoptosis after S . pneumoniae phagocytosis, and these effects correlated with reduced numbers of internalized bacteria . Chloramphenicol inhibition of protein synthesis by opsonized S . pneumoniae down-regulated subsequent MDM apoptosis . Phagocytosis of an unencapsulated mutant of S . pneumoniae resulted in increased MDM apoptosis, in association with enhanced internalization . Caspase inhibition was associated with decreased killing of bacteria . Enhanced induction of apoptosis by opsonized S . pneumoniae is the result of increased intracellular burden of bacteria, rather than of a specific pattern of engagement of complement receptor or FcgammaR . A dynamic interaction between live intracellular bacteria and the host cell is necessary for induction of apoptosis in MDMs, and induction of apoptosis contributes to the host defense against S . pneumoniae.

Gynecol Obstet Invest, 2003, 56(3), 173 - 8 Epub 2003 Oct 09.
Antimicrobial activity of human follicular fluids; Stepanovic S et al.; The aim of this study was to explore the antimicrobial activity of human follicular fluid (HFF), to test the hypothesis that different strains of the same bacterial species could display different patterns of susceptibility to antimicrobial action of HFF, and to preliminarily investigate the possible mechanism of antimicrobial action of this fluid . Antimicrobial activity of 60 samples of HFF toward 30 Streptococcus agalactiae strains was determined by the agar diffusion method and broth dilution method . To explore the mechanism of antimicrobial activity, biochemical analyses were performed with selected fluid samples . The obtained results indicate that 38.3% fluid samples did not inhibit bacterial growth, 53.3% showed moderate and 8.3% high antimicrobial activity . The tested effect of HFF on S . agalactiae strains was bactericidal and was not strain dependent . Lysozyme activity was detected in HFF exhibiting antimicrobial activity . There were no statistically significant differences in concentrations of estradiol, progesterone, transferrin, iron, total protein and albumin levels among tested samples regardless of the different rate of antimicrobial activity . The obtained results indicate that lysozyme is most probably a crucial antibacterial agent in this fluid; however, some other still unidentified factors may contribute to it .

Obstet Gynecol, 2003 Oct, 102(4), 753 - 60
Prenatal screening for infectious diseases and opportunities for prevention; Schrag SJ et al.; OBJECTIVE: To characterize adherence with recommendations for prenatal infectious disease screening and missed opportunities for prevention of congenital and perinatal infections . METHODS: Demographic, prenatal, and peripartum information was abstracted from labor and delivery records of a random, stratified sample of live births in 1998 and 1999 to residents of eight active surveillance areas . Adherence with prenatal screening recommendations was evaluated for hepatitis B, syphilis, rubella, human immunodeficiency virus (HIV), and group B streptococcus (GBS) . Characteristics of missed opportunities for disease prevention were assessed by univariate and multivariable analysis to account for survey design . RESULTS: Prenatal screening rates for hepatitis B surface antigen (HBsAg) (96.5%), syphilis (98.2%), and rubella (97.3%) were high . Areas of excess syphilis morbidity did not adhere to recommendations for third-trimester retesting . Testing rates for HIV (57.2%) and GBS (52.0%) were lower and had wide geographic variation . Postpartum rubella vaccination was documented for only 65.7% of rubella-susceptible women . Inadequate prenatal care was the single strongest predictor of missed opportunities for prenatal testing (relative risk 14.6; 95% confidence interval 6.3, 33.7) . Blacks were less likely than whites to receive adequate prenatal care and prenatal tests, more likely to test positive for HBsAg and syphilis, and less likely to receive recommended prevention interventions such as postpartum rubella vaccination for susceptible women . CONCLUSIONS: Adherence to both long-standing and more recent recommendations for congenital and perinatal disease prevention can be improved, thus perhaps reducing racial disparities in the use of prenatal screening and appropriate prevention interventions.

Int J Pediatr Otorhinolaryngol, 2003 Oct, 67(10), 1075 - 82
Noticeable differences in bacterial defence on tonsillar surfaces between bacteria-induced and virus-induced acute tonsillitis; Stenfors LE et al.; OBJECTIVE: Oral and pharyngeal cavities harbor a commensal bacterial flora which is kept in check by several innate and acquired agents . In this study, we focused on the proportions in which some antibacterial moderators (lysozyme, lactoferrin, IgG and S-IgA) coat the tonsillar surface bacteria in healthy individuals, in patients with acute tonsillitis (AT) culture-positive for Streptococcus pyogenes, and in patients with infectious mononucleosis (IM) caused by Epstein-Barr virus (EBV) . METHODS: Bacterial samples were collected for aerobic culturing and immunocytochemical evaluation from the tonsillar surfaces of eight healthy individuals (four males, four females; age range 16-22 years), eight patients with current AT (two males, six females; age range 16-29 years) and seven patients with IM (four males, three females; age range 15-21 years) . The immunocytochemical assay was based on gold-labeled antiserum to human lysozyme, lactoferrin, IgG and S-IgA followed by gold particle tracing in the transmission electron microscope . RESULTS: During AT, a significant increase in lysozyme coating (P<0.05) and lactoferrin coating (P<0.0005) of the bacteria was noted, whereas the S-IgA coating was significantly reduced (P<0.0005) . During IM infection, a significant increase in lactoferrin coating was noted (P<0.0005) whereas immunoglobulin coating was significantly reduced (IgG P<0.025; S-IgA P<0.0005) compared with healthy controls . During IM, all antibacterial moderators evaluated were significantly reduced compared with the situation during AT . CONCLUSIONS: Noticeable changes in the local innate and acquired bacterial defence system were observed during tonsillar infections, particularly during IM.

Int J Gynaecol Obstet, 2003 Nov, 83(2), 165 - 9
Intrapartum chlorhexidine vaginal irrigation and chorioamnion and placental microbial colonization; Rouse DJ et al.; OBJECTIVES: To determine whether intrapartum chlorhexidine vaginal irrigation reduces microbial colonization of the chorioamnion or placenta . METHODS: Secondary analysis was made of a randomized trial . Cultures for aerobic and anaerobic bacteria, Mycoplasma species and Ureaplasma urealyticum were performed using standard isolation techniques . RESULTS: The placentas of 83 trial participants allocated to chlorhexidine and 93 allocated to placebo underwent evaluation . These two groups were statistically balanced for risk factors for infection . Aerobic bacteria were isolated from 47% of the chlorhexidine placentas vs . 51% of the placebo placentas (relative risk 0.9, 95% confidence interval 0.7-1.3), anaerobic bacteria from 30% and 35%, respectively (0.8, 0.5-1.3), group B streptococcus from 12% and 15% (0.8, 0.4-1.7), U . urealyticum from 18% and 29% (0.6, 0.4-1.1), Mycoplasma species from 6% and 11% (0.6, 0.2-1.6), and any organism from 57% and 67%, respectively (0.8, 0.7-1.1) . CONCLUSIONS: Intrapartum chlorhexidine vaginal irrigation was associated with non-significant reductions in the rates of placental microbial isolation.

J Vet Med B Infect Dis Vet Public Health, 2003 Sep, 50(7), 343 - 6
Bacteriological status of canine milk and septicaemia in neonatal puppies--a retrospective study; Schafer-Somi S et al.; Results of the bacteriological examination of milk samples from 46 bitches were evaluated retrospectively, and correlated with findings of the bacteriological examination of organs from dead, septicaemic puppies in their litters (n = 33) . The aim of this study was to investigate, in how many cases of clinical and subclinical mastitis of the bitches, the same bacteria can be detected in their septicaemic neonates . One group of lactating bitches was clinically healthy (group I, n = 38), whereas in eight bitches different puerperal disorders were found (group II) . Twenty-five septicaemic puppies were from group I, eight from group II . Out of a broad spectrum of bacteria isolated from the milk of clinically healthy and diseased bitches, only Escherichia coli, Klebsiella pneumoniae and/or ss-haemolytic (haem.) Streptococcus sp . could be isolated from organs of their septicaemic puppies . This was the case in three bitches with mastitis and in one clinically healthy bitch only . Staphylococcus intermedius, although frequently isolated from canine milk, does not seem to be a cause of septicaemia in neonates . It is assumed that in most cases of neonate septicaemia, bacteria from the bitches' milk are not the primary cause.

Cutis, 2003 Sep, 72(3), 240 - 4
Comparison of azithromycin and cefadroxil for the treatment of uncomplicated skin and skin structure infections; Jennings MB et al.; In this multicenter, investigator-blind trial, we compared the efficacy and safety of azithromycin and cefadroxil for the treatment of uncomplicated skin and skin structure infections (SSSIs) . A total of 296 patients were randomized to receive either azithromycin (500 mg on day 1, followed by 250 mg once a day on days 2 to 5) or cefadroxil (500 mg twice a day for 10 days) . Outpatients, ranging in age from 18 to 75 years, with acute uncomplicated SSSIs were enrolled in the study . Clinical and bacteriologic response was assessed between days 10 and 13 (primary end point) and between days 28 and 32 . In a modified intent-to-treat analysis, clinical success rates assessed between days 10 and 13 were 97% (111/114) for azithromycin and 96% (101/105) for cefadroxil (P = .717) . For azithromycin and cefadroxil, corresponding rates of bacteriologic eradication for Staphylococcus aureus were 94% (64/68) and 86% (60/70), respectively, and for Streptococcus pyogenes, 80% (4/5) and 100% (6/6), respectively . Clinical success rates assessed between days 28 and 32 were 100% (82/82) for azithromycin compared with 90% (75/83) for cefadroxil (P = .007) . Corresponding rates of eradication for S aureus were 100% (59/59) versus 89% (56/63), respectively; and for S pyogenes, 100% (4/4) versus 83% (5/6), respectively . The incidence of treatment-related adverse events was similar in the 2 treatment groups . However, 5 of the 139 patients (4%) in the cefadroxil group discontinued therapy because of treatment-related adverse events compared with none of the 152 patients in the azithromycin group (P = .02) . Five-day therapy with azithromycin was as effective as 10-day therapy with cefadroxil for treating uncomplicated SSSIs.

Adv Exp Med Biol, 2001, 491, 473 - 84
The conformational epitope of type III group B Streptococcus capsular polysaccharide; Zou W et al.; In order to further characterize the conformational epitope of GBSPIII, we synthesized various oligosaccharides with the GBSPIII-related structures by a tailor-assembly synthetic scheme and a more traditional block-wise chemo-enzymatic approach . The oligosaccharides were used to probe the conformational epitope of GBSPIII using number of complementary techniques . The protective epitope of GPSPIII was further defined as length-dependent and conformational . The results of the studies confirmed that two repeating units (2RU) is the minimum binding unit and the epitope optimization mainly takes place between chain length 2RU to 7RU . Epitope optimization and multivalency were observed between 7RU and 20RU . The data support our hypothesis that the conformational epitope is an extended helical segment of the GBSPIII . GBSPIII exists mainly in the random coil form, which structurally mimics short oligosaccharide self-antigens, but it can infrequently and spontaneously form extended helices . Although not prevalent in GBSPIII the immune system preferentially selects these helical epitopes because they are unique to the polysaccharide.

Lijec Vjesn, 2003 May-Jun, 125(5-6), 134 - 7
{Streptococcus suis infection, a zoonosis we should have in mind--2 case reports}; Kopic J et al.; Streptococcus suis is primarily pig's pathogen, but can cause disease in a man exposed to contact with pigs (butchers, abatoir workers, farmers) . Infection in man is most frequently manifested as purulent meningitis, with deafness and ataxia, but there are rare reports on septic shock with multiple organ failure and death . We report two patients with Streptococcus suis type 1 infection, treated in "Dr Josip Bencevic" General Hospital, Slavonski Brod . The first patient suffered a very abrupt and severe illness, with septic shock, multiple organ failure and lethal outcome . The second patient had purulent meningitis with deafness . Both of them had a defect in immunologic function before infection . They were probably infected during manipulation with pork meat at home . Our patients had infection with Streptococcus suis type 1, contrary to reports on prevalent human infection with type 2 . It is necessary to make epidemiologic survey on human infection with that pathogen, especially in those professionally exposed to pigs and pork meat.

Can J Cardiol, 2003 Sep, 19(10), 1139 - 45
Infective endocarditis due to Streptococcus bovis in a series of nonaddict patients: clinical and morphological characteristics of 20 cases and review of the literature; Gonzalez-Juanatey C et al.; BACKGROUND AND OBJECTIVES: Controversy frequently exists about the actual frequency of Streptococcus bovis infective endocarditis (IE), its incidence of malignancy and its outcome . Consequently, the characteristics of S bovis IE were examined in an unselected population of nondrug-addicted patients . The literature was also reviewed . METHODS: Nondrug-addicted patients with S bovis IE were retrospectively reviewed . Clinically definite IE was diagnosed according to the Duke classification criteria at the single reference hospital for a defined population in northwestern Spain over a 13-year period . The clinical features, need for surgery and mortality rate of these patients were compared with those of other nondrug-addicted patients with IE examined during the same time period . RESULTS: Between 1987 and 1999, S bovis IE was diagnosed in 20 consecutive patients . This pathogen was responsible for 16.8% of the cases of definite IE in nondrug-addicted patients . Underlying conditions and embolic septic events were common . The aortic valve was the most common site of IE . Simultaneous involvement of two cardiac valves and moderate to severe regurgitation were more common in patients with S bovis IE . Colonic neoplasms were observed in 77% of patients . However, in-hospital mortality rate, need for in-hospital surgery and surgery during follow-up did not differ between patients with S bovis IE and the other nondrug-addicted patients with IE . CONCLUSIONS: In unselected patients, the rate of mortality due to S bovis IE is similar to that observed in IE due to other microorganisms . However, colonoscopic evaluation during admission and follow-up is required.

Am J Obstet Gynecol, 2003 Sep, 189(3 Suppl), S24 - 30
New concepts in vulvodynia; Edwards L; Vulvodynia is chronic vulvar burning/pain without clear medical findings . The etiology of vulvodynia is unknown and health care professionals should thoroughly rule out specific, treatable causes or factors such as dermatoses or group B Streptococcus infections . Vulvodynia is divided into 2 classes: vulvar vestibulitis syndrome is vestibule-restricted burning/pain and is elicited by touch; dysesthetic vulvodynia is burning/pain not limited to the vestibule and may occur without touch/pressure . After diagnosis, critical factors in successful patient management include education and psychological support/counseling . Unfortunately, clinical trials on potential vulvodynia therapies have been few . Standard therapy includes treating neuropathic pain (eg, tricyclic medications, gabapentin) thought to play a role . Additional therapies may be considered: pelvic floor rehabilitation combined with surface electromyography, interferon alfa, estrogen creams, and surgery . Importantly, any therapy should be accompanied by patient education and psychological support . Because definitive data on effective therapies are lacking, further clinical investigations of treatment options are warranted.

J Med Microbiol, 2003 Nov, 52(Pt 11), 975 - 80
Evaluation of a new serotyping kit for Streptococcus pneumoniae; Mudany MA et al.; A new serotyping test kit (Streptococcus pneumoniae antisera "Seiken" set; Denka kit) was evaluated for 285 strains of Streptococcus pneumoniae in comparison with the standard capsular reaction (Quellung test) . This new kit is based on the slide-agglutination method and is composed of eight pool sera, 40 group or type sera and 41 specific type sera . All serotyping results by using the Denka kit were completely identical to those obtained by using the conventional Quellung test . For types and groups, sensitivity and specificity were 100 and 100 %, respectively . For specific types, sensitivity and specificity were 100 and 100 %, respectively . The Denka kit is relatively rapid (mean test time, 5 min, versus 15 min by Quellung test), cheap (0.5 US$ per test, versus 1.4 US$ per Quellung test), easy to perform and does not require special equipment . The Denka kit may be useful for fieldworkers in developing countries involved in epidemiological surveys and vaccine development.

J Clin Microbiol, 2003 Oct, 41(10), 4888 - 91
Molecular characterization of a strain of group a streptococcus isolated from a patient with a psoas abscess; Lau SK et al.; We report the first case of a primary group A streptococcus (GAS) psoas abscess in a 31-year-old woman . The psoas abscess was preceded by an episode of acute pharyngitis . The M-protein gene (emm) and streptolysin S structural gene (sagA) were present in the isolate, with no significant amino acid differences from previously described sequences of M1 GAS isolates . Multilocus sequence typing (MLST) showed that the isolate belonged to MLST sequence type (MLST-ST) 28, the predominant MLST-ST associated with invasive disease caused by M1 isolates.

J Clin Microbiol, 2003 Oct, 41(10), 4858 - 61
Molecular analysis of group A streptococcal isolates associated with scarlet fever in southern Taiwan between 1993 and 2002; Yan JJ et al.; Collected between 1993 and 2002 at a Taiwanese university hospital, 77 group A streptococcus isolates associated with scarlet fever were grouped by emm typing and pulsed-field gel electrophoresis . The predominance of an emm1 clone before 1996 and the presence of genetically diverse emm1 and emm4 strains thereafter were found.

J Clin Microbiol, 2003 Oct, 41(10), 4655 - 9
emm typing of M nontypeable invasive group A streptococcal isolates in Israel; Moses AE et al.; We performed emm typing of M nontypeable invasive group A streptococcal (GAS) isolates collected in a prospective population-based study in Israel . One hundred twenty of 131 isolates (92%) had emm sequences compatible with GAS, consisting of 51 different emm types . Eleven isolates were found to be group G streptococcus . Of the 120 isolates, 55 (46%) belonged to 32 types for which there were no typing sera available in the Streptococcal Reference Laboratory in Israel . The other 65 (64%) isolates, consisting of 19 types, had sera available and therefore could have been serotyped . Forty-three isolates had T and emm types which were not correlated according to standard M-typing protocols and were therefore missed . The principal effect of emm typing was the addition of 32 types not previously identified in Israel and the discovery of new associations between emm and T types . emm typing did not significantly change the proportion of M types; the five most common types were 3, 28, 2, 62, and 41 . Twenty different types comprised 80% of all isolates . No new emm sequences were discovered . emm typing emphasized the unusually low incidence of M1 strains causing severe disease in Israel . As serological typing of GAS becomes more problematic due to lack of sera and the appearance of new emm types, reference laboratories should replace M typing with emm sequence typing . Development of a GAS vaccine relies on the emm type distributions in different geographical locations . In our study, 7% of isolates (types 41 and 62) are not included in a 26-valent vaccine that is being studied.

Mol Diagn, 2003 Mar, 7(1), 9 - 15
Isolation of pneumococcal DNA from nasopharyngeal samples for real-time, quantitative PCR : comparison of three methods; Saukkoriipi A et al.; Background: Real-time PCR is a useful method for detecting and quantifying bacterial DNA in clinical samples . DNA extraction is a crucial step when performing quantitative PCR.Methods: We compared three methods, QIAamp((R))The use of tradenames is for product identification purposes only and does not imply endorsement . DNA Mini kit, MagNAPure trade mark LC DNA Isolation Kit II together with PickPen trade mark magnetic particle transfer device, and KingFisher((R)) genomic DNA purification Kit with KingFisher((R)) mL instrument, for purification of Streptococcus pneumoniae DNA from 50 nasopharyngeal swab samples, collected into skim milk-tryptone-glucose-glycerin medium . Pneumococcal DNA was detected and quantified by real-time PCR and results were compared to culture findings.Results: The 22 (44%) pneumococcal culture-positive specimens were all positive by PCR regardless of DNA extraction method used, except that one KingFisher-extracted sample was positive only when repeatedly tested . Additionally, 71%, 57%, and 82% of the culture-negative samples were positive by real-time PCR when DNA was extracted by QIAamp, MagNAPure-PickPen, and KingFisher methods, respectively . The number of genome equivalents detected by real-time PCR varied, but was mainly low in culture-negative samples . The sensitivities of culture and real-time PCR were hence compared by analyzing different dilutions of a pneumococcal suspension . Real-time PCR detected significantly higher numbers of genome equivalents than the numbers of bacteria detected by culture.Conclusions: The results indicate that the DNA extraction method used for quantitative PCR should be evaluated and that real-time PCR is more sensitive than bacterial culture for detecting pneumococcus in nasopharyngeal swab samples.

Chin Med J (Engl), 2003 Sep, 116(9), 1304 - 7
Prevalence of antimicrobial resistance of Streptococcus pneumoniae in Chinese children: four hospitals surveillance; Shen X et al.; OBJECTIVE: To investigate the nasal carriage of antibiotic-resistant pneumococci in children of < 5 years old in the following four cities, Beijing, Shanghai, Guangzhou and Xi'an . METHODS: A total of 647 pneumococci strains were isolated and detected . Minimal inhibition concentrations (MICs) of antibiotics were determined by E-test . Disk diffusion test was used for the measurement of antimicrobial susceptibility . RESULTS: Prevalence of penicillin non-susceptible Streptococcus pneumoniae in the four cities was 41%, with Guangzhou (60.8%) ranking first, followed by Xi'an (45%), Shanghai (37%) and Beijing (25.9%) . The majority of penicillin non-susceptibility isolates (23.9% - 53.8%) had a low level of resistance (MIC 0.64 - 1.5 microg/ml) . The most sensitive antimicrobials in terms of percentage of susceptible organisms were amoxicillin-clavulanic acid (99.4%), followed by ceftriaxone (92.1%); cefurxime and cefaclor were slightly more sensitive than penicillin with susceptibility of 74.8% and 77.9% . Erythromycin, tetracycline and TMP-SMZ were highly resistant (83.6%, 82.1% and 76.2% respectively) . Among erythromycin resistant isolates, 100% were resistant to azithromycin, 98.6% to clarithromycin, 97.2% to roxithromycin and spiramycin, and 96.6% to clindamycin . 97.2% (141/145) were typical of the macrolides-lincosamides-streptogramons B (MLSB) resistance phenotype, and 2.8% (4/145) were M phenotype . The group of PRSP was with significantly higher rates of non-susceptibility for ceftriaxone (18.4%), cefurxime (58.6%), cefaclor (53.4%), compared with the group of PEN-S (0.5%, 1.8% and 0.2%, respectively) and the rate of multi-drug resistance in the isolates of PRSP group (92.9%) was significantly higher than that of PEN-S group (59.2%) . CONCLUSION: The rates of penicillin and multi-drug resistance among isolates of pneumococci carried nasally in are high children and the high prevalence of multi-drug resistance in the Chinese population may be becoming one of the most serious problems in this century.

Altern Ther Health Med, 2003 Sep-Oct, 9(5), 68 - 79
Efficacy of extract of Pelargonium sidoides in children with acute non-group A beta-hemolytic streptococcus tonsillopharyngitis: a randomized, double-blind, placebo-controlled trial; Bereznoy VV et al.; BACKGROUND: Clinical trial data suggest that antibiotics are not indicated for the treatment of acute non-group A beta hemolytic strep (non-GABHS) tonsillopharyngitis . Nevertheless patients are symptomatic and effective alternatives for its treatment are needed that have been evaluated in clinical trials . OBJECTIVE: To confirm that treatment with an extract of Pelargonium sidoides (EPs 7630) is superior to placebo for the treatment of non-GABHS tonsillopharyngitis in children . DESIGN: Randomized, double-blind, placebo-controlled trial . SETTING: Six study sites in 4 pediatric and ENT primary care outpatient clinics . PATIENTS: One hundred forty-three children aged 6-10 years with non-GABHS tonsillopharyngitis present < or = 48 h, a negative rapid strep screen, a Tonsillopharyngitis Severity Score (TSS) > or = 8 points, and informed consent . INTERVENTION: EPs 7630 or placebo (20 drops tid) for 6 days . MEASUREMENT: The primary outcome criterion was the decrease of the TSS from baseline (day 0) to day 4 . RESULTS: The decrease of the TSS from baseline (day 0) to day 4 was 7.1 +/- 2.1 points under EPs 7630 (n = 73), and 2.5 +/- 3.6 points under placebo (n = 70) . The covariate adjusted decrease was 7.0 +/- 2.4 points under EPs 7630, and 2.9 +/- 2.4 points under placebo . The 95% RCI for the difference between the groups was {2.7; 4.9} demonstrating a significant difference in efficacy of EPs 7630 compared to placebo (P < 0.0001) . Adverse events (AEs) occurred in 15/143 patients (EPs 7630: 4/73 patient, placebo: 44/70) and were not related to the investigational medication . CONCLUSIONS: EPs 7630 was superior compared to placebo for the treatment of acute non-GABHS tonsillopharyngitis in children . Treatment with EPs 7630 reduced the severity of symptoms and shortened the duration of illness by at least 2 days.

J Cardiol, 2003 Sep, 42(3), 129 - 33
{Prosthetic valve endocarditis caused by Streptococcus constellatus infection complicated with perivalvular abscess: serial observation by transesophageal echocardiography: a case report}; Ejima K et al.; A 61-year-old man was admitted to an associated hospital because of fever . He had undergone aortic valve and mitral valve replacement 6 years ago, because of rheumatic aortic valve stenosis, and mitral valve stenosis and regurgitation . He had prosthetic valve endocarditis caused by a rare Streptococcus constellatus infection complicated by multiple organ failure and systemic embolism . We considered that surgical treatment was difficult, and continued antibiotic treatment . The inflammatory reaction and fever improved . Prosthetic valve endocarditis is often difficult to identify and treat . Streptococcus constellatus infection is characterized by destruction and formation of abscess . We followed up the patient by transesophageal echocardiography, and observed the course of change of the paravalvular abscess around the aortic valve from echogenic to echolucent.

J Midwifery Womens Health, 2003 Sep-Oct, 48(5), 357 - 9
Group A streptococcus and streptococcal toxic shock syndrome: a postpartum case report; Golden S; Streptococcal toxic shock syndrome from group A streptococcal disease is rare in the postpartum period, yet it is associated with high morbidity and mortality . Early diagnosis and treatment can lessen complications . Midwives can improve provision of postpartum care by being adequately educated about signs and symptoms of this disease, thereby enhancing their ability to recognize it and obtain the appropriate referral or collaborative medical care . A clinical presentation of postpartum streptococcal toxic shock syndrome, including provider follow-up, is presented.

J Bacteriol, 2003 Oct, 185(20), 6209 - 14
Characterization of divIVA and other genes located in the chromosomal region downstream of the dcw cluster in Streptococcus pneumoniae; Fadda D et al.; We analyzed the chromosome region of Streptococcus pneumoniae located downstream of the division and cell wall (dcw) cluster that contains the homolog of the Bacillus subtilis cell division gene divIVA and some genes of unknown function . Inactivation of divIVA in S . pneumoniae resulted in severe growth inhibition and defects in cell shape, nucleoid segregation, and cell division . Inactivation of the ylm genes resulted in some morphological and/or division abnormalities, depending on the inactivated gene . Transcriptional analysis revealed a relationship between these genes and the ftsA and ftsZ cell division genes, also indicating that the connection between the dcw cluster and the divIVA region is more extensive than just chromosomal position and gene organization.

J Bacteriol, 2003 Oct, 185(20), 6137 - 46
ATP-bound conformation of topoisomerase IV: a possible target for quinolones in Streptococcus pneumoniae; Sifaoui F et al.; Topoisomerase IV, a C(2)E(2) tetramer, is involved in the topological changes of DNA during replication . This enzyme is the target of antibacterial compounds, such as the coumarins, which target the ATP binding site in the ParE subunit, and the quinolones, which bind, outside the active site, to the quinolone resistance-determining region (QRDR) . After site-directed and random mutagenesis, we found some mutations in the ATP binding site of ParE near the dimeric interface and outside the QRDR that conferred quinolone resistance to Streptococcus pneumoniae, a bacterial pathogen . Modeling of the N-terminal, 43-kDa ParE domain of S . pneumoniae revealed that the most frequent mutations affected conserved residues, among them His43 and His103, which are involved in the hydrogen bond network supporting ATP hydrolysis, and Met31, at the dimeric interface . All mutants showed a particular phenotype of resistance to fluoroquinolones and an increase in susceptibility to novobiocin . All mutations in ParE resulted in resistance only when associated with a mutation in the QRDR of the GyrA subunit . Our models of the closed and open conformations of the active site indicate that quinolones preferentially target topoisomerase IV of S . pneumoniae in its ATP-bound closed conformation.

J Bacteriol, 2003 Oct, 185(20), 6057 - 66
Positive correlation between tyrosine phosphorylation of CpsD and capsular polysaccharide production in Streptococcus pneumoniae; Bender MH et al.; CpsA, CpsB, CpsC, and CpsD are part of a tyrosine phosphorylation regulatory system involved in modulation of capsule synthesis in Streptococcus pneumoniae and many other gram-positive and gram-negative bacteria . Using an immunoblotting technique, we observed distinct laddering patterns of S . pneumoniae capsular polysaccharides of various serotypes and found that transfer of the polymer from the membrane to the cell wall was independent of size . Deletion of cps2A, cps2B, cps2C, or cps2D in the serotype 2 strain D39 did not affect the ability to transfer capsule to the cell wall . Deletion of cps2C or cps2D, which encode two domains of an autophosphorylating tyrosine kinase, resulted in the production of only short-chain polymers . The function of Cps2A is unknown, and the polymer laddering pattern of the cps2A deletion mutants appeared similar to that of the parent, although the total amount of capsule was decreased . Loss of Cps2B, a tyrosine phosphatase and a kinase inhibitor, resulted in an increase in capsule amount and a normal ladder pattern . However, Cps2B mutants exhibited reduced virulence following intravenous inoculation of mice and were unable to colonize the nasopharynx, suggesting a diminished capacity to sense or respond to these environments . In D39 and its isogenic mutants, the amounts of capsule and tyrosine-phosphorylated Cps2D (Cps2D approximately P) correlated directly . In contrast, restoration of type 2 capsule production followed by deletion of cps2B in Rx1, a laboratory passaged D39 derivative containing multiple uncharacterized mutations, resulted in decreased capsule amounts but no alteration in Cps2D approximately P levels . Thus, a factor outside the capsule locus, which is either missing or defective in the Rx1 background, is important in the control of capsule synthesis.

J Bacteriol, 2003 Oct, 185(20), 6016 - 24
Rgg coordinates virulence factor synthesis and metabolism in Streptococcus pyogenes; Chaussee MS et al.; Streptococcus pyogenes is a human-specific pathogen that relies on its host for metabolic substrates . Rgg-like proteins constitute a family of transcriptional regulators present in several gram-positive bacteria . In S . pyogenes, Rgg influences the expression of several virulence-associated proteins localized to the cell wall and extracellular environment . Secreted enzymes may degrade host macromolecules, thereby liberating metabolic substrates . To determine if Rgg regulation of exoprotein expression is associated with altered metabolism, the catabolic activities of S . pyogenes strain NZ131 (serotype M49) and an isogenic rgg mutant strain were analyzed during growth with complex and defined media . As expected, the wild-type strain preferentially used glucose and produced lactic acid during the exponential phase of growth . In contrast, the rgg mutant fermented arginine in the exponential phase of growth, even in the presence of glucose . Arginine degradation was associated with a neutral culture pH and excretion of NH(3) and ornithine . Arginine, serine, and asparagine were depleted from mutant cultures during growth . The addition of arginine and serine to culture media increased the growth yield and NH(3) production of mutant but not wild-type cultures . Addition of asparagine had no effect on the growth yield of either strain . Altered metabolism of arginine and serine in the mutant was associated with increased transcript levels of genes encoding arginine deiminase and a putative serine dehydratase . Thus, Rgg coordinates virulence factor synthesis and catabolic activity and may be important in the pathogen's adaptation to changes in the availability of metabolic substrates.

Enferm Infecc Microbiol Clin, 2003 Aug-Sep, 21(7), 329 - 33
{Experimental meningitis due to a high-level cephalosporin-resistant strain of Streptococcus pneumoniae serotype 23F}; Ribes S et al.; INTRODUCTION: The increasing prevalence of high-level cephalosporin-resistant strains of Streptococcus pneumoniae could complicate the treatment of severe infections such as meningitis . There are still questions as to the characteristics of these strains, their ability to produce severe infection, and the inflammatory response they induce in CSF . METHODS: Using a rabbit model of meningitis, we sought to determine the pathogenicity and differences in inflammatory parameters in two serotype 23F S . pneumoniae strains with different susceptibility to betalactams . Minimal inhibitory concentrations of the two strains were as follows: strain A--PEN 4 micro g/mL, CRO/CTX 2 micro g/mL--and strain B--PEN 0.12 micro g/mL, CRO/CTX 32 micro g/mL . RESULTS: Strain A resulted in a greater incidence of secondary bacteremia and higher inflammatory parameters during the early phases of infection . Strain B caused brain edema, a more severe inflammatory response and significantly higher mortality at the end of the experiment . CONCLUSIONS: Both strains induced meningitis in the animal model . The differences in inflammatory response produced by the two strains could be related to the variations that determine the betalactam resistance level.

Clin Infect Dis, 2003 Oct 15, 37(8), 1029 - 36 Epub 2003 Sep 24.
Recurrent invasive pneumococcal disease: a population-based assessment; King MD et al.; We sought to define the risk of recurrence of invasive pneumococcal disease (IPD) and to define the characteristics of persons experiencing recurrent IPD through population-based surveillance . Cases of IPD were identified through the US Centers for Disease Control and Prevention's Active Bacterial Core Surveillance . Recurrent episodes were defined as isolation of Streptococcus pneumoniae from any normally sterile site > or =30 days after initial positive culture . Among 13,924 persons who survived their initial episode of IPD, 318 (2.3%) experienced > or =1 subsequent episode, for 376 total recurrences . The recurrence rate was 1294 episodes per 100,000 person-years, or 50 times the annual incidence of IPD . In multivariable analysis, a higher risk of recurrence was seen in persons infected with human immunodeficiency virus and in children <5 years old with chronic illness . Most (92%) persons with recurrence had a vaccine indication . The risk of recurrence among certain persons with IPD is extremely high.

HNO, 2003 Oct, 51(10), 806 - 12 Epub 2003 Apr 11.
{Reliability and general practice value of 2 rapid Streptococcus A tests}; Schmuziger N et al.; Rapid streptococcal-A-antigen detection assays have good specificity (over 90 percent) but moderate sensitivity (between 80 and 90 percent), when the tests are compared with a standard throat culture . Contradictory results have been found for one of the more recent tests, the optical immune assay Strep A OIA MAX, while for 6 years, we have been using the immune assay Strep A Plus.Results of the optical immunoassay and the conventional immune assay Strep A Plus were compared in 65 patients with acute pharyngitis . A standard culture was used as reference and confirmed by enhanced broth culturing and nucleic acid hybridization assay (Gen-Probe) when the two detection assays produced contradictory results.While both assays were equally sensitive (78.3%), Strep A OIA MAX and Strep A Plus had a similar specificity of 95.2% and 100%, respectively.Four and nine steps were required for Strep A Plus and for Strep A OIA MAX test procedures, respectively with results being available in 4-5 min and in 9-10 min, respectively.We conclude that both rapid immunoassays have a similar reliability while the handling of the Strep A Plus is much simpler than the handling of the Strep A OIA MAX . Neither rapid immunoassays are sensitive enough to eliminate the need for backup cultures.

Pediatrics, 2003 Oct, 112(4), 982 - 6
Bullous myringitis: a case-control study; McCormick DP et al.; Prior studies have shown that bullous myringitis (BM) accounts for <10% of acute otitis media (AOM) cases, and that the distribution of viral and bacterial pathogens in BM is similar to that in AOM without BM, except for a relative increase in the proportion of Streptococcus pneumoniae in BM . We studied 518 cases of AOM in children aged 6 months to 12 years . Using tele-otoscopy to assist the diagnosis, we identified 41 cases (7.9%) with BM . Children who had AOM with BM were older than AOM patients without BM (median age: 4.3 years vs 18 months) . We compared 41 cases of AOM with BM to 41 control cases of age-, race-, and gender-matched AOM patients without BM . When compared with this matched control group, children with BM had more severe symptoms at the time of diagnosis and were more likely to have bulging of the tympanic membrane in the quadrants that were not obscured by the bulla . Children with AOM and BM may require aggressive pain management . Although parents and clinicians may agree that a watchful waiting approach is appropriate for older children with mild AOM, children experiencing painful AOM with BM may not be successful candidates for a watchful-waiting approach, because parents may resist postponement of antibiotic therapy in children who are more symptomatic.

Pediatrics, 2003 Oct, 112(4), 862 - 9
Antibiotic-resistant Streptococcus pneumoniae in the heptavalent pneumococcal conjugate vaccine era: predictors of carriage in a multicommunity sample; Finkelstein JA et al.; OBJECTIVE: Despite immunization with heptavalent pneumococcal conjugate vaccine (PCV7), the rising prevalence of antibiotic resistance makes Streptococcus pneumoniae a continuing threat to child health . Data on carriage of resistant organisms by healthy children in communities in which immunization with PCV7 has been implemented will help to define and decrease these risks further . METHODS: Children who were <7 years old, resided in a study community, and presented for routine well care or a "sick" visit between March 13 and May 11, 2001, at 31 primary care practices in 16 geographically distinct Massachusetts communities were studied . Consenting parents provided demographic information and data on potential risk factors for carriage of S pneumoniae and of penicillin-nonsusceptible S pneumoniae (PNSP) . S pneumoniae isolates from nasopharyngeal specimens were tested for resistance to commonly used antibiotics including penicillin, ceftriaxone, erythromycin, and trimethoprim/sulfamethoxazole . Isolates were serotyped and grouped into PCV7-included serotypes, potentially cross-reactive serotypes (ie, an organism of a serogroup included in the vaccine), or non-PCV7 serotypes . Diagnosis on the day of collection, history of recent antibiotic use, and history of PCV7 immunization were obtained by chart review . Separate bivariate and multivariate analyses were performed to identify correlates of colonization with S pneumoniae and colonization with PNSP, accounting for clustering within communities . RESULTS: S pneumoniae was isolated from the nasopharynx of 190 (26%) of the 742 children studied . Of the 166 tested, 33% were nonsusceptible to penicillin, with 14% showing intermediate susceptibility (minimum inhibitory concentration {MIC} 0.12-1.0) and 19% fully resistant (MIC > or =2) . Nonsusceptibility to other antibiotics was common, including ceftriaxone (14%), erythromycin (22%), and trimethoprim/sulfa (31%); 20% of S pneumoniae isolates were not susceptible to > or =3 antibiotics . Thirty-six percent of isolates were of serotypes covered by PCV7; 30% were of PCV7 serogroups and potentially cross-reactive, but not 1 of the 7 included serotypes; and 34% were unrelated to PCV7 serogroups . Nonsusceptibility to penicillin was more common in PCV7-included strains (45%) and potentially cross-reactive strains (51%) than in non-PCV7 serotypes (8%) . Risk factors for PNSP colonization included child care attendance (odds ratio {OR}: 3.9; 95% confidence interval {CI}: 2.3-6.5), current respiratory tract infection (OR: 4.7; 95% CI: 2.5-8.6), and recent antibiotic use (OR: 1.7; 95% CI: 1.0-2.8) . PCV7 immunization was associated with decreased carriage of PCV7-included serotypes but not with an overall decrease in S pneumoniae colonization or with a decline in PNSP colonization . CONCLUSIONS: In this multicommunity sample, pneumococcal antibiotic resistance was common and was most frequently found in PCV7-included and PCV7 serogroup strains . The long-term impact of PCV7 immunization will be partially determined by the protection that it affords against invasive infection with potentially cross-reactive serotypes, as well as the virulence and future resistance patterns of unrelated serotypes.

J Biol Chem, 2003 Dec 12, 278(50), 50596 - 606 Epub 2003 Sep 30.
Structures of Streptococcus pneumoniae hyaluronate lyase in complex with chondroitin and chondroitin sulfate disaccharides . Insights into specificity and mechanism of action; Rigden DJ et al.; Streptococcus pneumoniae hyaluronate lyase is a surface enzyme of this Gram-positive bacterium . The enzyme degrades hyaluronan and chondroitin/chondroitin sulfates by cleaving the beta1,4-glycosidic linkage between the glycan units of these polymeric substrates . This degradation helps spreading of this bacterial organism throughout the host tissues and facilitates the disease process caused by pneumococci . The mechanism of this degradative process is based on beta-elimination, is termed proton acceptance and donation, and involves selected residues of a well defined catalytic site of the enzyme . The degradation of hyaluronan alone is thought to proceed through a processive mode of action . The structures of complexes between the enzyme and chondroitin as well as chondroitin sulfate disaccharides allowed for the first detailed insights into these interactions and the mechanism of action on chondroitins . This degradation of chondroitin/chondroitin sulfates is nonprocessive and is selective for the chondroitin sulfates only with certain sulfation patterns . Chondroitin sulfation at the 4-position on the nonreducing site of the linkage to be cleaved or 2-sulfation prevent degradation due to steric clashes with the enzyme . Evolutionary studies suggest that hyaluronate lyases evolved from chondroitin lyases and still retained chondroitin/chondroitin sulfate degradation abilities while being specialized in the degradation of hyaluronan . The more efficient processive degradation mechanism has come to be preferred for the unsulfated substrate hyaluronan.

Diagn Microbiol Infect Dis, 2003 Oct, 47(2), 407 - 14
A quantitative LightCycler PCR to detect Streptococcus pneumoniae in blood and CSF; van Haeften R et al.; A quantitative real-time PCR targeting the Pneumolysin (ply) gene of Streptococcus pneumoniae was developed for the LightCycler instrument using Fluorescence Resonance Energy Transfer (FRET) probes . All common S . pneumoniae serotypes were detected while other bacteria and viruses were not . The sensitivity was determined to be between one and ten target copies per reaction . The PCR was applied to six CSF and 16 whole blood specimens from 17 patients with laboratory proven invasive pneumococcal disease . One hundred percent of CSF specimens and 69% of whole blood specimens were PCR positive . The bacterial loads were determined to be 7.6 to 6.01 x 10(5) copies/microL for the six CSF specimens, and 0.08 to 5.4 x 10(2) copies/microL for the 16 whole blood specimens . Ninety-seven percent of 30 culture and Gram's stain negative CSF specimens and 100% of 50 normal whole blood specimens were PCR negative . This highly sensitive and specific PCR assay has the potential to provide sufficiently rapid results to improve antibiotic treatment of S.pneumoniae infections, while bacterial load quantitation has opened up exciting possibilities for patient management.

FEMS Immunol Med Microbiol, 2003 Oct 15, 38(3), 205 - 13
Role of M3 protein in the adherence and internalization of an invasive Streptococcus pyogenes strain by epithelial cells; Eyal O et al.; Streptococcus pyogenes utilizes multiple mechanisms for adherence to and internalization by epithelial cells . One of the molecules suggested of being involved in adherence and internalization is the M protein . Although strains of the M3 serotype form the second largest group isolated from patients with severe invasive diseases and fatal infections, not much information is known regarding the interactions of M3 protein with mammalian cells . In this study we have constructed an emm3 mutant of an invasive M3 serotype (SP268), and demonstrated that the M3 protein is involved in both adherence to and internalization by HEp-2 cells . Fibronectin promoted both adherence and internalization of SP268 in an M3-independent pathway . Utilizing speB and speB/emm3 double mutants, it was found that M3 protein is not essential for the maturation of SpeB, as was reported for the M1 protein . Increased internalization efficiency observed in both the speB and emm3/speB mutants suggested that inhibition of S . pyogenes internalization by SpeB is not related to the presence of an intact M3 protein . Thus, other proteins in SP268, which serve as targets for SpeB activity, have a prominent role in the internalization process.

Microb Pathog, 2003 Nov, 35(5), 203 - 15
Characterization of a bovine lactoferrin binding protein of Streptococcus uberis; Moshynskyy I et al.; The interaction between Streptococcus uberis and bovine lactoferrin (bLf) has been characterized . The binding of 125I-bLf to S . uberis was time-dependent and displaceable by unlabeled bLf . The Scatchard plot was linear and approximately 7,800 binding sites were expressed by each bacterial cell, with an affinity of 1.0 x 10(-7) M . Both heat and protease treatment of bacterial cells reduced bLf-binding significantly, indicating the presence of a cell surface localized protein receptor for the glycoprotein . One protein was identified from the cell wall of S . uberis as the functionally active bLf-binding protein and it existed in both monomeric and dimeric forms . The recombinant protein expressed in E . coli cells was able to bind bLf and had molecular weights similar to that of native S . uberis . Deletion analysis located the bLf-binding domain to a 200 amino acid region at the amino terminus of Lbp . Analysis of the primary and secondary structure suggested that Lbp is an M-like protein . An isogenic mutant of S . uberis lacking the internal sequence of the lbp gene was constructed by allele replacement . Adherence experiments with wild type S . uberis and the lbp mutant revealed that Lbp is not responsible for attachment of S . uberis to host epithelial cells.

Pediatr Dermatol, 2003 Sep-Oct, 20(5), 389 - 92
Frequency and clinical role of Staphylococcus aureus overinfection in atopic dermatitis in children; Ricci G et al.; The goal of this study was to evaluate the frequency and role of Staphylococcus aureus infection in patients with atopic dermatitis (AD) . In 81 children, ages 2 months to 9 years, affected with moderate to severe AD, 308 samples from the cutaneous lesions were obtained and analyzed . S . aureus was isolated in 52 children (64.2%) . Five of these were also colonized by Streptococcus pyogenes and one by Candida albicans . In 61 patients, total IgE serum level and specific IgE were tested to evaluate their allergic status: in 43 children a diagnosis of extrinsic AD was made, while 18 were affected by intrinsic AD . A higher presence of the bacterium was observed in allergic (71%) versus nonallergic children (49%) . Our data demonstrate the importance of S . aureus in the clinical manifestation of AD and, in particular, its role in worsening the eczematous lesions of the face, neck, and perineum in children less than 1 year of age.

Expert Opin Pharmacother, 2003 Oct, 4(10), 1847 - 55
Gatifloxacin in community-acquired respiratory tract infection; Sethi S; Gatifloxacin (Tequin, Kyorin Pharmaceutical Co . Ltd) is a new fluoroquinolone with a broad spectrum of activity for pathogens implicated in community-acquired respiratory tract infections, including Gram-positive, -negative and atypical bacteria . Excellent oral bioavailability, a half-life allowing once-daily administration and excellent penetration into respiratory tissues are desirable pharmacokinetic characteristics of gatifloxacin . Monte Carlo simulation of gatifloxacin in Streptococcus pneumoniae infection demonstrates that adequate levels of pharmacokinetic/pharmacodynamic parameters are obtained with gatifloxacin in almost all instances . In randomised, controlled trials and a large open-label, community-based study, gatifloxacin has shown excellent clinical and bacteriological efficacy in acute bacterial sinusitis, acute exacerbations of chronic bronchitis and community-acquired pneumonia . Current guidelines recommend the initial empiric use of gatifloxacin (along with the other new fluoroquinolones) for community-acquired respiratory tract infection in patients who have increased likelihood of infection with resistant pathogens . Another group of patients where this agent is recommended for initial antimicrobial therapy are those who, because of underlying disease and/or comorbid conditions, need an antibiotic with high antimicrobial efficacy to achieve optimal outcomes.

Pediatr Pulmonol, 2003 Nov, 36(5), 384 - 90
Pneumonia due to Chlamydia pneumoniae in children: epidemiology, diagnosis, and treatment; Hammerschlag MR; The term "atypical" pneumonia has been used to differentiate infections caused by Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionella, and other related organisms from pneumonia caused by classic bacteria, the prototype being Streptococcus pneumoniae . However, recent studies demonstrated that the clinical presentation of pneumonia due to atypical pathogens cannot readily be differentiated from those caused by "typical" bacteria . This is further complicated by the observation that coinfections with atypical pathogens and other bacteria are frequent . Nonetheless, the term "atypical" can be useful, as these organisms share a number of characteristics that separate them from "typical" bacteria . They are either obligate or facultative intracellular parasites that cannot be isolated using routine microbiologic methods . The most commonly used method of diagnosis of these infections is serology, which has significant limitations . Although C . pneumoniae is now recognized worldwide as a common cause of respiratory infections in adults and children, major gaps remain in our knowledge of the biology of this organism and how it causes disease, in major part due to the lack of readily available, standardized diagnostic methods .

Ann Neurol, 2003 Oct, 54(4), 451 - 8
Meningitis-associated hearing loss: protection by adjunctive antioxidant therapy; Klein M et al.; Hearing loss is the most frequent long-term complication of pneumococcal meningitis, affecting up to 40% of survivors . Unfortunately, adjuvant therapy with dexamethasone has failed to satisfactorily reduce its incidence . Therefore, we evaluated the use of antioxidants for the adjunctive therapy of meningitis-associated deafness . Eighteen hours after intracisternal injection of 7.5 x 10(5) colony-forming units of Streptococcus pneumoniae, rats were treated systemically either with ceftriaxone and the antioxidants and peroxynitrite scavengers Mn(III)tetrakis(4-benzoic acid)-porphyrin (MnTBAP) or N-acetyl-L-cysteine (NAC) or placebo (1 ml phosphate-buffered saline) for 4 days . Hearing was assessed by auditory brainstem response audiometry . Adjunctive antioxidant therapy significantly reduced the long-term hearing loss (14 days after infection) for square wave impulses (mean hearing loss +/- SD: ceftriaxone and placebo, 45+/-26 dB; ceftriaxone and MnTBAP, 9+/-23 dB; ceftriaxone and NAC, 19+/-30 dB) as well as 1 kHz (ceftriaxone and placebo, 28+/-19 dB; ceftriaxone and MnTBAP, 10+/-16 dB; ceftriaxone and NAC, 10+/-17 dB), and 10 kHz tone bursts (ceftriaxone and placebo, 62+/-27 dB; ceftriaxone and MnTBAP, 16+/-13 dB; ceftriaxone and NAC, 25+/-26 dB) . Furthermore, both antioxidants attenuated the morphological correlates of meningogenic hearing loss, namely, long-term blood-labyrinth barrier disruption, spiral ganglion neuronal loss, and fibrous obliteration of the perilymphatic spaces . Adjuvant antioxidant therapy is highly otoprotective in meningitis and therefore is a promising future treatment option.

Laryngoscope, 2003 Oct, 113(10), 1780 - 5
Nasopharyngeal flora and drug susceptibility in children with macrolide therapy; Iino Y et al.; OBJECTIVES/HYPOTHESIS: Low-dose, long-term administration of macrolides (macrolide therapy) has been used as an effective treatment for chronic respiratory tract diseases . The authors reported on the nasopharyngeal flora in children treated with macrolide therapy . STUDY DESIGN: Prospective study . METHODS: Nasopharyngeal cultures were obtained from 73 children with chronic rhinosinusitis and/or otitis media with effusion at the end of the low-dose administration of clarithromycin (macrolide group) . As control subjects, 98 children with chronic rhinosinusitis and/or otitis media with effusion who were not given macrolides were also included in the study . The culture results were evaluated with respect to antimicrobial susceptibility patterns, risk factors for carriage of erythromycin-resistant Streptococcus pneumoniae, and the clinical efficacy of the therapy . RESULTS: The macrolide therapy did not have a significant effect on the incidence or the susceptibility patterns of potential pathogens except for Moraxella catarrhalis . Most of children in the macrolide group possessed a normal flora compared with the control children . The risk factors for carriage of erythromycin-resistant S pneumoniae were male gender in the macrolide group and age under 6 years and use of antimicrobial drugs other than macrolides in the control group . The clinical efficacy of the therapy was independent of carriage of erythromycin-resistant S pneumoniae . CONCLUSION: Macrolide therapy has little effect on carriage of drug-resistant pathogens, and the efficacy of the therapy depends on the anti-inflammatory effect of the drugs, which is independent of their antimicrobial effect.

J Antimicrob Chemother, 2003 Nov, 52(5), 809 - 12 Epub 2003 Sep 30.
Telithromycin post-antibiotic and post-antibiotic sub-MIC effects for 10 Gram-positive cocci; Jacobs MR et al.; Post-antibiotic effects (PAE) and post-antibiotic sub-MIC effects (PA-SME) of the ketolide telithromycin (HMR 3647) were determined for 10 Gram-positive cocci with various macrolide resistance mechanisms, including inducible and constitutive ribosomal methylase and macrolide efflux resistance genes . Strains tested included four Streptococcus pneumoniae, three Streptococcus pyogenes and three Staphylococcus aureus . Telithromycin MICs were 0.008-0.015 mg/L for pneumococci, 0.015-4.0 mg/L for S . pyogenes and 0.03 mg/L for staphylococci . PAE were determined after exposure of strains at 10 x MIC for 1 h . PA-SME were determined in the presence of 0.12x, 0.25x and 0.5x MIC of the agent after the initial 1 h exposure period . The PAE of telithromycin varied from 0.3 to 3.8 h; the PA-SME varied from 0.8 to 4.6 h, with maximal PA-SME varying from 1.5 to 4.6 h . PAE tended to be shortest for S . pyogenes (0.4-2.7 h) and S . aureus (0.3-2.4 h), compared to 1.5-3.8 h for S . pneumoniae . The duration of the PA-SME was similar for the three species tested . The low MICs for many strains as well as the PAE and PA-SME demonstrated in this study for telithromycin show promise for increasing the dosing interval of this ketolide, but will need verification by pharmacokinetic/pharmacodynamic and clinical studies.

Emerg Infect Dis, 2003 Sep, 9(9), 1159 - 62
Fluoroquinolone and macrolide treatment failure in pneumococcal pneumonia and selection of multidrug-resistant isolates; Perez-Trallero E et al.; Streptococcus pneumoniae serotype 3, isolated from a penicillin-allergic patient and initially susceptible to fluoroquinolones, macrolides, lincosamides, quinupristin-dalfopristin, and telithromycin, became resistant to all these drugs during treatment . Mutations in the parC and gyrA and in the 23S rRNA and the ribosomal protein L22 genes were detected in the resistant isolates.

Emerg Infect Dis, 2003 Sep, 9(9), 1089 - 95
Aggregated antibiograms and monitoring of drug-resistant Streptococcus pneumoniae; Van Beneden CA et al.; Community-specific antimicrobial susceptibility data may help monitor trends among drug-resistant Streptococcus pneumoniae and guide empiric therapy . Because active, population-based surveillance for invasive pneumococcal disease is accurate but resource intensive, we compared the proportion of penicillin-nonsusceptible isolates obtained from existing antibiograms, a less expensive system, to that obtained from 1 year of active surveillance for Georgia, Tennessee, California, Minnesota, Oregon, Maryland, Connecticut, and New York . For all sites, proportions of penicillin-nonsusceptible isolates from antibiograms were within 10 percentage points (median 3.65) of those from invasive-only isolates obtained through active surveillance . Only 23% of antibiograms distinguished between isolates intermediate and resistant to penicillin; 63% and 57% included susceptibility results for erythromycin and extended-spectrum cephalosporins, respectively . Aggregating existing hospital antibiograms is a simple and relatively accurate way to estimate local prevalence of penicillin-nonsusceptible pneumococcus; however, antibiograms offer limited data on isolates with intermediate and high-level penicillin resistance and isolates resistant to other agents.

Eur J Biochem, 2003 Oct, 270(20), 4164 - 72
Characterization of the 16S rRNA- and membrane-binding domains of Streptococcus pneumoniae Era GTPase: structural and functional implications; Hang JQ et al.; Era is a highly conserved GTPase essential for bacterial growth . The N-terminal part of Era contains a conserved GTPase domain, whereas the C-terminal part of the protein contains an RNA- and membrane-binding domain, the KH domain . To investigate whether the binding of Era to 16S rRNA and membrane requires its GTPase activity and whether the GTPase domain is essential for these activities, the N- and C-terminal parts of the Streptococcus pneumoniae Era - Era-N (amino acids 1-185) and Era-C (amino acids 141-299), respectively - were expressed and purified . Era-C, which had completely lost GTPase activity, bound to the cytoplasmic membrane and 16S rRNA . In contrast, Era-N, which retained GTPase activity, failed to bind to RNA or membrane . These results therefore indicate that the binding of Era to RNA and membrane does not require the GTPase activity of the protein and that the RNA-binding domain is an independent, functional domain . The physiological effects of the overexpression of Era-C were assessed . The Escherichia coli cells overexpressing Era and Era-N exhibited the same growth rate as wild-type E . coli cells . In contrast, the E . coli cells overexpressing Era-C exhibited a reduced growth rate, indicating that the overexpression of Era-C inhibits cell growth . Furthermore, overexpression of era-N and era-C resulted in morphological changes . Finally, purified Era and Era-C were able to bind to poly(U) RNA, and the binding of Era to poly(U) RNA was significantly inhibited by liposome, as the amount of Era bound to the RNA decreased proportionally with the increase of liposome in the assay . Therefore, this study provides the first biochemical evidence that both binding sites are overlapping . Together, these results indicate that the RNA- and membrane-binding domain of Era is a separate, functional entity and does not require the GTPase activity or the GTPase domain of the protein for activity.

J Biomed Mater Res A, 2003 Oct 1, 67(1), 18 - 25
Quantitative evaluation of bacteria adherent to polyelectrolyte HEMA-based hydrogels; Berlutti F et al.; The use of adhesive poly(HEMA)-based hydrogels is standard practice in dental restorative procedures . Microorganisms, which potentially can cause oral pathologies, may colonize these polymers . In the present work, bacterial adhesion to polymers prepared with 2-hydroxyethyl methacrylate (HEMA) and to different molar ratios of 2-acrylamido-2-methylpropane-sulfonic acid (AMPS) and/or to 2-methacryloyloxyethyl-tri-methyl-ammonium chloride (METAC) co-monomers were tested . A colorimetric assay system that utilizes the Microbo revelation medium (Microbo srl, Rome, Italy) for microbial counts is shown to be capable of counting the number of adherent bacterial cells without removing them from polymer surfaces . In conditions that mimic those present in the oral cavity, similar bacterial adhesion percentages on the same polymer were observed with the different bacteria belonging to both gram-positive and gram-negative genera, such as Streptococcus sobrinus and Streptococcus oralis (resident microorganisms in the oral cavity) and Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa (transient microorganisms in the oral cavity) . It is determined that the physico-chemical characteristics of poly(HEMA)-based hydrogels are the major factors promoting bacterial adhesion, which increased with increasing water content in the swollen polymers, reaching maximal values on the cationic polymers .

Angiogenesis, 1998, 2(3), 219 - 33
Functional studies on the anti-pathoangiogenic properties of CM101; Yan HP et al.; Group B streptococcus (GBS) isolated from human neonates diagnosed with sepsis and respiratory distress produces a polysaccharide exotoxin (CM101) which has been previously described as GBS toxin . CM101 infused i.v . into tumor-bearing mice causes rapid tumor neovascularitis, infiltration of inflammatory cells, inhibition of tumor growth and tumor apoptosis . CM101 has successfully completed phase I studies in refractory cancer patients with very encouraging results . We have now demonstrated a mechanism of action for CM101 . Using a normal mouse tumor model, we have examined tumor and normal tissues which were harvested at 0, 5, 15, 30 and 60min post-infusion of either CM101 or dextran . We present evidence that CM101 is rapidly (within the first 5min) bound to the tumor neovasculature . Complement is activated by the alternative pathway (C3) and leukocytes start to infiltrate the tumor within the first 5min . Through RT-PCR and immunohistochemical techniques, we demonstrate that proinflammatory cytokines, interleukin-6 and tumor necrosis factor (TNF)-alpha, are up-regulated in infiltrating leukocytes and TNF receptor 2 is up- regulated in the targeted tumor neovasculature . Combined, these events constitute possible explanations for the observed pathophysiology of tumor ablation.

J Exp Med, 2003 Oct 6, 198(7), 1057 - 68 Epub 2003 Sep 29.
Evasion of phagocytosis through cooperation between two ligand-binding regions in Streptococcus pyogenes M protein; Carlsson F et al.; The M protein of Streptococcus pyogenes is a major bacterial virulence factor that confers resistance to phagocytosis . To analyze how M protein allows evasion of phagocytosis, we used the M22 protein, which has features typical of many M proteins and has two well-characterized regions binding human plasma proteins: the hypervariable NH2-terminal region binds C4b-binding protein (C4BP), which inhibits the classical pathway of complement activation; and an adjacent semivariable region binds IgA-Fc . Characterization of chromosomal S . pyogenes mutants demonstrated that each of the ligand-binding regions contributed to phagocytosis resistance, which could be fully explained as cooperation between the two regions . Deposition of complement on S . pyogenes occurred almost exclusively via the classical pathway, even under nonimmune conditions, but was down-regulated by bacteria-bound C4BP, providing an explanation for the ability of bound C4BP to inhibit phagocytosis . Different opsonizing antisera shared the ability to block binding of both C4BP and IgA, suggesting that the two regions in M22 play important roles also under immune conditions, as targets for protective antibodies . These data indicate that M22 and similar M proteins confer resistance to phagocytosis through ability to bind two components of the human immune system.

Vet Microbiol, 2003 Oct 8, 96(1), 103 - 13
A novel family of fibrinogen-binding proteins in Streptococcus agalactiae; Jacobsson K; Streptococcus agalactiae is a contagious pathogen in bovine mastitis . It is also one of the leading causes to neonatal pneumonia, sepsis and meningitis in Europe and North America . Although extracellular bacterial proteins that interact with host structures are putative vaccine components, so far only a few receptins have been identified and characterised from this organism . The aim of the present study was to identify fibrinogen-binding receptins from a shotgun phage display library constructed from the bovine type strain CCUG 4208 . A novel extracellular receptin was identified after selecting the library against bovine fibrinogen . This protein is a member of a family of at least three proteins that share the fibrinogen-binding region as well as the N-terminal signal sequence, whereas the intervening region varies in size and has almost no sequence similarity . Proteins of this family are present also in human isolates of S . agalactiae, although binding to human fibrinogen has not been detected.

Scand J Infect Dis, 2003, 35(8), 452 - 8
Capsular types and antibiotic susceptibility of invasive Streptococcus pneumoniae among children in Sweden; Hedlund J et al.; To investigate the serotype distribution and antibiotic susceptibility patterns 204 isolates of Streptococcus pneumoniae obtained from blood or cerebrospinal fluid (CSF) of children < or = 18 y of age were collected from 19 clinical microbiological laboratories in Sweden during the years 1998-2001 . 166 isolates were from blood only, and 38 isolates were from CSF . The most common serotypes found were 6B, 1, 7F, 14, 18C, 19F, 6A, 4, 23F, 9V and 19A, in descending order of frequency . During the study period serotype 6B increased in frequency from 14.3% in 1998 to 28.3% in 2001 and serotype 1 decreased simultaneously from 20.4% to 9.4% . Serotype 1 was the most common serotype among children > or = 2 y of age or older, but was not found among children < 2 y of age . The potential coverage rate for the heptavalent pneumococcal conjugate vaccine varied between 53 and 68% during the studied years, and was higher for children < 2 y of age (74%) than for older children (51%) . The majority of isolates were susceptible to penicillin and other antibiotics tested.

Hua Xi Kou Qiang Yi Xue Za Zhi, 2003 Aug, 21(4), 277 - 80
{Scanning electron microscope observation of morphological influence P-aminobenzoic acid (PABA) on Porphyromonas gingivalis}; Wang Z et al.; OBJECTIVE: In order to investigate the effect of PABA produced by Streptococcus sanguis on microecological balance of subgingival plaque, different concentrations of PABA were applied to see if it can influence the form and adherence of P . gingivalis . METHODS: After adding different concentrations of PABA into 1/2 concentration of BHI media, an anaerobic technique was used to culture P . gingivalis . P . gingivalis grew in the medium was observed by a scanning electron microscope . RESULTS: Excessively high or low PABA concentration could influence the form and adherence of P . gingivalis . CONCLUSION: PABA produced by Streptococcus sanguis can affect the form and adherence of P . gingivalis . It indicates that Streptococcus sanguis plays regulative effect on the microecological balance of subgingival plaques.

J Arthroplasty, 2003 Sep, 18(6), 813 - 5
Late infection of a total knee arthroplasty with Streptococcus bovis in association with carcinoma of the large intestine; Vince KG et al.; Infection of a total knee arthroplasty with Streptococcus bovis in a 76-year-old man that led to the diagnosis of a bowel carcinoma is reported . Investigation revealed a malignancy in the ascending colon with extension into the adrenal gland . S bovis in conjunction with colonic neoplasia has been reported in several orthopedic conditions: vertebral osteomyelitis, discitis, lateral neck abscess, and osteomyelitis of the ileum . The relationship of S bovis to endocarditis, meningitis, brain abscesses, and peritonitis has also been well described . However, S bovis is a rare pathogen infecting joint prostheses and should raise the possibility of a gastrointestinal lesion.

J Infect Dis, 2003 Oct 1, 188(7), 1049 - 53 Epub 2003 Sep 15.
Beta-hemolysin-independent induction of apoptosis of macrophages infected with serotype III group B streptococcus; Ulett GC et al.; Group B streptococcus (GBS) induces apoptosis in macrophages . Growth conditions minimizing beta-hemolysin expression, such as high glucose, reduce apoptosis . We constructed an isogenic mutant strain of GBS 874391 lacking the beta-hemolysin structural gene cylE and investigated the role that beta-hemolysin plays in apoptosis of J774 macrophages . Viability of macrophages infected with wild-type or cylE GBS was similar and significantly less than that of macrophages infected with GBS grown in high-glucose media . Thus, apoptosis in GBS-infected macrophages is dependent not on beta-hemolysin but on a factor coregulated with beta-hemolysin by glucose.

J Infect Dis, 2003 Oct 1, 188(7), 1040 - 8 Epub 2003 Sep 17.
Penicillin enhances the toll-like receptor 2-mediated proinflammatory activity of Streptococcus pneumoniae; Moore LJ et al.; The Streptococcus pneumoniae cell-wall components peptidoglycan and lipoteichoic acid activate Toll-like receptor 2 (TLR2), which transduces an inflammatory response . After exposure to penicillin, type 2 S . pneumoniae strain D39, but not the isogenic autolysin-deficient mutant AL2, induced significantly enhanced interleukin-8 promoter activity in TLR2-transfected HeLa cells . Lag-phase D39 exhibited enhanced TLR2 activation after exposure to penicillin at levels below the minimum inhibitory concentration (MIC); in contrast, early log-phase S . pneumoniae were most active when exposed to the MIC . This enhancement was not ablated by heat treatment but was attenuated by autolysin inhibitors . The antimicrobial activity of moxifloxacin and erythromycin was not associated with TLR2 activation by S . pneumoniae . These data show that penicillin treatment of S . pneumoniae releases proinflammatory cell-wall components that activate TLR2 and that this activity is dependent on autolysin, the growth phase of the organism, and the antibiotic concentration.

J Infect Chemother, 2003 Sep, 9(3), 221 - 6
In vitro activities of new ketolide, telithromycin, and eight other macrolide antibiotics against Streptococcus pneumoniae having mefA and ermB genes that mediate macrolide resistance; Ubukata K et al.; The comparative in vitro activity of a new ketolide, telithromycin (TEL), and eight other macrolide-lincosamide antibiotics (MLS) against 215 strains, of Streptococcus pneumoniae including penicillin-resistant isolates (PRSP), was determined by the agar dilution method . These strains were isolated from patients with pneumonia, otitis media, and purulent meningitis between 1995 and 1997 . Two genes, mefA and ermB, that encode MLS resistance in the strains were identified by polymerase chain reaction (PCR) . Of the strains, 30.2% (n = 65) had the mefA gene, 37.7% (n = 81) had the ermB gene, and 1.4% (n = 3) had both resistant genes . The minimum inhibitory concentration (MIC90s) of TEL and 16-membered ring MLS for strains having the mefA gene were 0.063-0.25 microg/ml, which were the same level as those for MLS-susceptible strains . On the other hand, the strains with the mefA gene showed low-level resistance to 14- and 15-membered ring MLS, with MIC90s ranging from 1 to 4 microg/ml . Only the MIC90 of TEL at 0.5 microg/ml, for strains having the ermB gene was superior to that of the 14-, 15-, and 16-membered ring MLS (MIC90, > or =64 microg/ml) . TEL also showed excellent activity against PRSP having abnormal pbp1a, pbp2x, and pbp2b genes . Most strains having the mefA and ermB genes were serotyped to 3, 6, 14, 19, and 23 . These results suggest that TEL may be a useful chemotherapeutic agent for respiratory tract infections caused by S . pneumoniae.

J Infect Chemother, 2003 Sep, 9(3), 210 - 4
The effect of pharmacokinetic/pharmacodynamic (PK/PD) parameters of gatifloxacin on its bactericidal activity and resistance selectivity against clinical isolates of Streptococcus pneumoniae; Ebisu H et al.; The impact of the pharmacokinetic/pharmacodynamic (PK/PD) parameters (the 24h area under the concentration-time curve {AUC24h}/minimum inhibitory concentration {MIC} and maximum concentration in serum {Cmax}/MIC ratio) after single oral dosing of gatifloxacin on its bactericidal activity and resistance selectivity against quinolone-susceptible clinical isolates of Streptococcus pneumoniae J-69 was investigated using an in vitro PK model . The MICs of gatifloxacin, levofloxacin, and ciprofloxacin were 0.25, 1, and 1 micro g/ml, respectively . When the range of AUC24h/MIC ratios was varied from 9.0 to 36 with a constant Cmax/MIC ratio of 3.4, the bactericidal activity was correlated with the AUC24h/MIC ratios . Eradication was observed at an AUC24h/MIC ratio of 36 . On the other hand, the resistance selectivity was associated with the Cmax/MIC ratio . Mutant strains were selected at a Cmax/MIC ratio of 0.84, but not 1.7 with a constant AUC24h/MIC ratio of 9.0 . These results suggested that an AUC24h/MIC ratio of > or =36 and a Cmax/MIC ratio of > or =1.7 might be possible benchmarks to show enough bacterial eradication and prevention of emergence of resistant strains to gatifloxacin, respectively . When the serum concentrations after clinical oral dosing of gatifloxacin (200 mg b.i.d.), levofloxacin (100 mg t.i.d.), and ciprofloxacin (200 mg t.i.d.) were simulated, the bactericidal activity of gatifloxacin was higher than those of levofloxacin and ciprofloxacin . Moreover, no resistant strain was obtained by the exposure to gatifloxacin and levofloxacin, whereas ciprofloxacin selected resistant strains . The clinically relevant oral dosage of gatifloxacin was anticipated to result in a high AUC24h/MIC90 ratio of 81 and a Cmax/MIC90 ratio of 4.4, suggesting that this agent is clinically effective in the treatment of pneumococcal infections.

Int J Antimicrob Agents, 2003 Oct, 22 Suppl 1, S15 - 24; discussion S25-6
The epidemiology of antibiotic resistance in Streptococcus pneumoniae and the clinical relevance of resistance to cephalosporins, macrolides and quinolones; Pallares R et al.; Invasive non-meningeal pneumococcal infections remain a major cause of morbidity and mortality worldwide . The factors affecting the epidemiology and mortality of pneumococcal infections are discussed . The increase and spread of resistance to antimicrobial agents among pneumococci is a cause of concern to the clinician . There are links between the usage of antibacterial agents and the development of resistance . Resistance to penicillin and other beta-lactams has become widespread but this does not appear to have decreased the efficacy of some of these agents against non-meningeal infections . There is evidence that the good pharmacokinetic and pharmacodynamic features of the third generation cephalosporins (cefotaxime and ceftriaxone) contribute to their efficacy in vivo . New breakpoints for cefotaxime and ceftriaxone against non-meningeal pneumococcal isolates were proposed by the National Committee for Clinical Laboratory Standard (NCCLS, US), based on the clinical evidence of the efficacy of these drugs . In contrast there is increasing evidence that resistance to macrolides can lead to a poor clinical response . Fluoroquinolones have been widely used to treat respiratory tract infections among others, and pneumococcal resistance to these agents in vitro, although currently low, is increasing . There are reports that resistance to fluoroquinolones can develop during treatment and may be reflected in a lack of clinical response . Several clinical and epidemiological variables (e.g . prior antibiotic use) can be useful to identify patients at risk from infections with antibiotic-resistant pneumococci . These patients would be those who would benefit the most from a pneumococcal vaccination programme.

Int J Antimicrob Agents, 2003 Oct, 22 Suppl 1, S3 - 13; discussion S25-6
NCCLS perspectives in changing susceptibility breakpoints for antimicrobial drugs; Gums JG; The spread of resistance to many antimicrobial agents in various microbial species has been highlighted by the World Health Organisation and many government agencies around the world . The reasons for this increase and spread are complex and are discussed . A number of surveillance studies has monitored the increase in resistance among isolates of Streptococcus pneumoniae to various important classes of antimicrobials . These results are discussed with particular reference to penicillins, macrolides and fluoroquinolones . Although there is evidence that in vitro resistance to macrolides and more recently to fluoroquinolones may be associated with a reduced clinical efficacy, there is no such clear association with resistance to beta-lactams and lack of clinical efficacy in non-meningeal infections . Resistance or susceptibility to an antimicrobial agent is based on breakpoints and these are set in the US by the National Committee of Clinical and Laboratory Standards . In response to these recent clinical studies showing that non-meningeal pneumococcal infections with strains classified as resistant in vitro still responded well to treatment with various beta-lactams, new breakpoints have been set . Results are presented showing that using these breakpoints, the levels of resistance to the third generation cephalosporins, ceftriaxone and cefotaxime against a range of non-meningeal pneumococcal isolates were lower than those obtained using the previous breakpoints . The excellent pharmacokinetic and pharmacodynamic properties of these agents are believed to contribute to their good activity in the clinic.

Dermatol Ther, 2003, 16(3), 195 - 205
Cutaneous infections in the elderly: diagnosis and management; Weinberg JM et al.; Over the past several years there have been many advances in the diagnosis and treatment of cutaneous infectious diseases . This review focuses on the three major topics of interest in the geriatric population: herpes zoster and postherpetic neuralgia (PHN), onychomycosis, and recent advances in antibacterial therapy . Herpes zoster in adults is caused by reactivation of the varicella-zoster virus (VZV) that causes chickenpox in children . For many years acyclovir was the gold standard of antiviral therapy for the treatment of patients with herpes zoster . Famciclovir and valacyclovir, newer antivirals for herpes zoster, offer less frequent dosing . PHN refers to pain lasting > or = 2 months after an acute attack of herpes zoster . The pain may be constant or intermittent and may occur spontaneously or be caused by seemingly innocuous stimuli such as a light touch . Treatment of established PHN through pharmacologic and nonpharmacologic therapy will be discussed . In addition, therapeutic strategies to prevent PHN will be reviewed . These include the use of oral corticosteroids, nerve blocks, and treatment with standard antiviral therapy . Onychomycosis, or tinea unguium, is caused by dermatophytes in the majority of cases, but can also be caused by Candida and nondermatophyte molds . Onychomycosis is found more frequently in the elderly and in more males than females . There are four types of onychomycosis: distal subungual onychomycosis, proximal subungual onychomycosis, white superficial onychomycosis, and candidal onychomycosis . Over the past several years, new treatments for this disorder have emerged which offer shorter courses of therapy and greater efficacy than previous therapies . The treatment of bacterial skin and skin structure infections in the elderly is an important issue . There has been an alarming increase in the incidence of gram-positive infections, including resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and drug-resistant pneumococci . While vancomycin has been considered the drug of last defense against gram-positive multidrug-resistant bacteria, the late 1980s saw an increase in vancomycin-resistant bacteria, including vancomycin-resistant enterococci (VRE) . More recently, strains of vancomycin-intermediate resistant S . aureus (VISA) have been isolated . Gram-positive bacteria, such as S . aureus and Streptococcus pyogenes are often the cause of skin and skin structure infections, ranging from mild pyodermas to complicated infections including postsurgical wound infections, severe carbunculosis, and erysipelas . With limited treatment options, it has become critical to identify antibiotics with novel mechanisms of activity . Several new drugs have emerged as possible therapeutic alternatives, including linezolid and quinupristin/dalfopristin.

Isr Med Assoc J, 2003 Sep, 5(9), 646 - 8
Risk factors for carriage of group B streptococcus in southern Israel; Marchaim D et al.; BACKGROUND: In southern Israel, a discrepancy between a relatively high prevalence of Group B streptococcus maternal carriage (12.3%) and a very low incidence of neonatal disease (0.1/1,000 live births) has been found despite the fact that no preventive strategy has been implemented . OBJECTIVES: To determine the risk factors for maternal carriage in order to clarify this discrepancy and further examine the different aspects of GBS in southern Israel . METHODS: Cultures for GBS were obtained from 681 healthy pregnant women, and relevant demographic and obstetric data were collected . The medical records of 86 neonates born to carrier women were retrospectively examined . Statistical analysis was performed using the Pearson chi-square test . RESULTS: Women who were not born in Israel, particularly immigrants from the former USSR, were significantly prone to carry the pathogen compared to native Israeli women (Bedouins and Jews) (P = 0.03) . CONCLUSIONS: A high GBS transmission rate is expected among immigrants who came from areas with a high prevalence of maternal carriage to one with a low incidence of neonatal disease environment and were not subject to any preventive strategy . Clinical attention should be directed to this issue throughout Israel.

Isr Med Assoc J, 2003 Apr, 5(4), 268 - 71
Plantar puncture wounds in children: analysis of 80 hospitalized patients and late sequelae; Eidelman M et al.; BACKGROUND: Puncture wounds in the feet of children present a clinical dilemma . OBJECTIVES: To evaluate our approach, we reviewed the charts and all available images of 80 children admitted to our institution because of plantar punctures from 1988 to 1999 . METHODS: The charts of 80 children were reviewed retrospectively . RESULTS: Three groups of patients were found: 59 with superficial cellulitis, 11 with retained foreign bodies, and 10 with osteoinyelitis and/or septic arthritis . There was a significant presentation delay in patients from the second and third groups . Most common organisms were Staphylococcus aureus or Group A Streptococcus . Of the 80 children, 34 were treated surgically and 46 were treated with antibiotic therapy alone . All patients with osteomyelitis and septic arthritis were re-examined; at follow-up, all but one were asymptomatic apart from residual radiologic sequelae in four . CONCLUSIONS: Patients with an established infection 24-36 hours after a plantar puncture should be admitted to hospital for parenteral antibiotic therapy . Delayed presentation is a significant marker for deep-seated infection . Further infection or relapse after initial improvement suggests the presence of osteomyelitis or a retained foreign body . A bone scan is advisable in all patients with suspected osteomyelitis: a positive bone scan necessitates aggressive early debridement combined with appropriate antibiotics; while negative bone scan, X-ray and exploration suggest that the infection is due to a foreign body, which can be detected by computed tomography.

J Pediatr (Rio J), 2003 May-Jun, 79(3), 215 - 20
{Oropharyngeal carriage of Streptococcus pneumoniae by children attending day care centers in Taubate, SP: correlation between serotypes and the conjugated heptavalent pneumococcal vaccine}; Lucarevschi BR et al.; OBJECTIVE: Streptococcus pneumoniae usually colonizes the oropharynx of healthy people . Oropharyngeal carriage is related to the invasion of adjacent structures and to the development of invasive disease . A descriptive cross-sectional study was performed aiming at verifying the prevalence of oropharyngeal colonization by S . pneumoniae in children attending day care centers in the city of Taubate - SP; verifying the frequency of S . pneumoniae serotypes in isolated strains; and relating the most frequent serotypes to the composition of the conjugated heptavalent pneumococcal vaccine currently in use . METHODS: From June 29 to December 15 1998, samples of oropharyngeal material were collected from 987 children, ranging from 8 to 71 months old, enrolled in day care centers in Taubate - SP . The identification of S . pneumoniae was based on the observation of the colonies that presented partial hemolysis in agar-blood and agar-blood with gentamycin plates and on the observation of inhibited growth around the optochin disc . Serotyping was performed by the Quellung reaction, using specific antiserum, provided by the Centers for Disease Control and Prevention (Atlanta, GA/USA), and the Danish nomenclature system . RESULTS: S . pneumoniae was isolated from the oropharynx in 209 out of 987 children (colonization rate of 21.2%) . Twenty eight serotypes were identified . The seven most frequent serotypes were: 6A/6B (21.5%), 19F (14.8%), 18C (7.4%), 23F (7.4%), 9V (6.7%), 14 (5.2%), 10A (4.4%) . Except for serotype 10A, all the other six are included in the vaccine . The only vaccine serotype which was not found was serotype 4 . CONCLUSION: Agreement of 63% between the oropharynx colonizer serotypes and the serotypes present in the vaccine was found.

Presse Med, 2003 Aug 23, 32(27), 1273 - 5
{Acute Gemella haemolysans spondylodiscitis in an immunocompetent patient}; Martha B et al.; INTRODUCTION: Gemella is a commensal bacterium of the upper respiratory tract responsible for rare infections such as acute endocarditis and meningitis . We report the case of an acute Gemella haemolysans spondylodiscitis . OBSERVATION: A 72 year-old woman was hospitalised for an etiological control and treatment of acute L4-L5 spondylodiscitis with epiduritis, confirmed on MRI . The clinical picture was composed of backache with shivering and alteration in general status of health . The peripheral bacteriological samples, intra-dermal reaction and brucella serology were all negative . The surgical L5 biopsy, following bacteriological enrichment, isolated Gram-positive cocci, later identified as Gemella haemolysans . The antibiogram showed good sensitivity to amoxicillin, dalacin and erythromycin, and strong resistance to aminosides . The search for a contamination point was negative . The patient rapidly improved with antibiotics combining 6 g/d of amoxicillin and 1200 mg/d of clindamycin, and the biological and clinical signs regressed . The antibiotic bi-therapy was continued for two and a half months and then relayed to amoxicillin alone for two further weeks . COMMENTS: The first descriptions of Gemella haemolysans infection were made in the seventies . Cases of infectious endocarditis were succeeded by septicaemia on cirrhosis and later a few cases of acute post-neurosurgical meningitis . In the majority of cases, a dental contamination point was found . The difficulties in its etiological diagnosis, related to the problems in identifying this germ that has similar characteristics to Streptococcus viridans, suggests that the prevalence of Gemella haemolysans infections is greatly underrated . The sensitivity profile generally observed is sensitivity to penicillins and aminosides--the association of which is synergic--, to cyclines and glycopeptides, and resistance to trimethoprime-sulfamethoxazole.

Antimicrob Agents Chemother, 2003 Oct, 47(10), 3352 - 6
Postantibiotic, postantibiotic sub-MIC, and subinhibitory effects of PGE-9509924, ciprofloxacin, and levofloxacin; Odenholt I et al.; Postantibiotic effects (PAEs), postantibiotic sub-MIC effects, and sub-MIC effects of the new nonfluoroquinolone PGE-9509924, ciprofloxacin, and levofloxacin against gram-positive and gram-negative strains were investigated . In comparison to ciprofloxacin and levofloxacin, PGE-9509924 exerted very similar PAEs against all strains except for both strains of Streptococcus pneumoniae, where longer PAEs were found for PGE-9509924 . All three investigated quinolones showed no minimal PAEs against Pseudomonas aeruginosa.

Antimicrob Agents Chemother, 2003 Oct, 47(10), 3155 - 60
Clinical isolates of Streptococcus pneumoniae with different susceptibilities to ceftriaxone and cefotaxime; Karlowsky JA et al.; Ceftriaxone and cefotaxime are extended-spectrum cephalosporins previously demonstrated to possess very similar in vitro activities against Streptococcus pneumoniae . Anecdotal reports of isolates with divergent in vitro susceptibilities to ceftriaxone and cefotaxime have been published . To determine the prevalence of pneumococcal isolates with divergent ceftriaxone and cefotaxime susceptibilities, we tested 1,000 clinical isolates collected by U.S . laboratories in 2001-2002 by broth microdilution and E-test . The percentages of isolates susceptible to ceftriaxone and cefotaxime were significantly different by both broth microdilution (98.6 and 96.6%, respectively; P < 0.05) and E-test (98.3 and 95.8%; P < 0.001) . The differences observed were due solely to the activities of the two agents against penicillin-resistant isolates . Twenty-six of 188 penicillin-resistant isolates (13.8%) demonstrated different ceftriaxone and cefotaxime MIC interpretative phenotypes when tested by broth microdilution; 18 isolates were concurrently ceftriaxone susceptible and cefotaxime intermediate, 6 were ceftriaxone intermediate and cefotaxime resistant, and 2 were ceftriaxone susceptible and cefotaxime resistant (1.1% of penicillin-resistant isolates; 0.2% of all isolates tested) . Sixteen of the 26 isolates (65%) were from southern U.S . states . The 26 isolates had serogroups and serotypes (6, 9, 14, 19, and 23) commonly associated with penicillin-resistant isolates; SmaI pulsed-field gel electrophoresis identified 18 isolates (69%) dispersed among five subtype groups and 8 isolates that were unrelated to any of the other isolates . We conclude that certain isolates of penicillin-resistant pneumococci are less susceptible to cefotaxime than to ceftriaxone and that these isolates are not the result of the spread of a single clone . Whether such isolates have increased in prevalence over time remains unknown.

Antimicrob Agents Chemother, 2003 Oct, 47(10), 3104 - 8
Levofloxacin disposition in cerebrospinal fluid in patients with external ventriculostomy; Pea F et al.; In vitro levofloxacin exhibits both potent or intermediate activity against most of the pathogens frequently responsible for acute bacterial meningitis and synergistic activity with some beta-lactams . Since levofloxacin was shown to penetrate the cerebrospinal fluid (CSF) during meningeal inflammation both in animals and in humans, the disposition of levofloxacin in CSF was studied in 10 inpatients with external ventriculostomy because of communicating hydrocephalus related to subarachnoid occlusion due to cerebral accidents who were treated with 500 mg of levofloxacin intravenously twice a day because of extracerebral infections . Plasma and CSF concentration-time profiles and pharmacokinetics were assessed at steady state . Plasma and CSF levofloxacin concentrations were analyzed by high-pressure liquid chromatography . The peak concentration of levofloxacin at steady state (C(max ss))was 10.45 mg/liter in plasma and 4.06 mg/liter in CSF, respectively, with the ratio of the C(max ss) in CSF to the C(max ss) in plasma being 0.47 . The areas under the concentration-time curves during the 12-h dosing interval (AUC(0-tau)s) were 47.69 mg . h/liter for plasma and 33.42 mg . h/liter for CSF, with the ratio of the AUC(0-tau) for CSF to the AUC(0-tau) for plasma being 0.71 . The terminal-phase half-life of levofloxacin in CSF was longer than that in plasma (7.02 +/- 1.57 and 5.51 +/- 1.36 h, respectively; P = 0.034) . The ratio of the levofloxacin concentration in CSF to the concentration in plasma progressively increased with time, from 0.30 immediately after dosing to 0.99 at the end of the dosing interval . In the ventricular CSF of patients with uninflamed meninges, levofloxacin was shown to provide optimal exposure, which approximately corresponded to the level of exposure of the unbound drug in plasma . The findings provide support for trials of levofloxacin with twice-daily dosing in combination with a reference beta-lactam for the treatment of bacterial meningitis in adults . This cotreatment could be useful both for overcoming Streptococcus pneumoniae resistance and for enabling optimal exposure of the CSF to at least one antibacterial agent for the overall treatment period.

Antimicrob Agents Chemother, 2003 Oct, 47(10), 3099 - 103
Penetration of moxifloxacin into healthy and inflamed subcutaneous adipose tissues in humans; Joukhadar C et al.; The present study addressed the ability of moxifloxacin to penetrate into healthy and inflamed subcutaneous adipose tissues in 12 patients with soft tissue infections (STIs) . Penetration of moxifloxacin into the interstitial space fluid of healthy and inflamed subcutaneous adipose tissues was measured by use of in vivo microdialysis following administration of a single intravenous dosage of 400 mg in six diabetic and six nondiabetic patients with STIs . For the entire study population, the mean time-concentration profile of free moxifloxacin in plasma was identical to the time-concentration profile of free moxifloxacin in tissue (P was not significant) . For healthy and inflamed adipose tissues for the diabetic subgroup, the mean moxifloxacin areas under the concentration-time curves (AUCs) from 0 to 8 h (AUC(0-8)s) were 8.1 +/- 7.1 and 3.7 +/- 1.9 mg.h/liter, respectively (P was not significant) . The ratios of the mean AUC(0-8) for inflamed tissue/AUC(0-8) for free moxifloxacin in plasma were 0.5 +/- 0.4 for diabetic patients and 1.2 +/- 0.8 for nondiabetic patients (P was not significant) . The ratios of the AUCs from 0 to 24 h for free moxifloxacin in plasma/MIC at which 90% of isolates are inhibited were >58 and 121 h for Streptococcus species and methicillin-sensitive Staphylococcus aureus, respectively . Concentrations of moxifloxacin effective against clinically relevant bacterial strains are reached in plasma and in inflamed and healthy adipose tissues . Thus, the pharmacokinetics of moxifloxacin in tissue and plasma support its use for the treatment of STIs in diabetic and nondiabetic patients.

J Am Chem Soc, 2003 Oct 1, 125(39), 11872 - 8
The structure of NADH in the enzyme dTDP-d-glucose dehydratase (RmlB); Beis K et al.; The structure of Streptococcus suis serotype type 2 dTDP-d-glucose 4,6-dehydratase (RmlB) has been determined to 1.5 A resolution with its nicotinamide coenzyme and substrate analogue dTDP-xylose bound in an abortive complex . During enzyme turnover, NAD(+) abstracts a hydride from the C4' atom of dTDP-glucose-forming NADH . After elimination of water, hydride is then transferred back to the C6' atom of dTDP-4-keto-5,6-glucosene-regenerating NAD(+) . Single-crystal spectroscopic studies unambiguously show that the coenzyme has been trapped as NADH in the crystal . Electron density clearly demonstrates that in contrast to native structures of RmlB where a flat nicotinamide ring is observed, the dihydropyridine ring of the reduced cofactor in this complex is found as a boat . The si face, from which the pro-S hydride is transferred, has a concave surface . Ab initio electronic structure calculations demonstrate that the presence of an internal hydrogen bond, between the amide NH on the nicotinamide ring and one of the oxygen atoms on a phosphate group, stabilizes this distorted conformation . Additionally, calculations show that the hydride donor ability of NADH is influenced by the degree of bending in the ring and may be influenced by an active-site tyrosine residue (Tyr 161) . These results demonstrate the ability of dehydratase enzymes to fine-tune the redox potential of NADH through conformational changes in the nicotinamide ring.

J Endod, 2003 Sep, 29(9), 562 - 4
The effect of passive ultrasonic activation of 2% chlorhexidine or 5.25% sodium hypochlorite irrigant on residual antimicrobial activity in root canals; Weber CD et al.; Ninety-four single-canal roots were prepared using the step-down technique . Forty-two canals were irrigated with 2% chlorhexidine, 42 canals with 5.25% sodium hypochlorite (NaOCl), and 10 control canals with phosphate-buffered saline (PBS) . The chlorhexidine and NaOCl groups were each then equally divided into a final irrigation group and a 1-min passive ultrasonic irrigation group . Canals were enlarged with a Parapost drill . The apical 3-5 mm was covered with nail polish . Canals were rinsed with PBS, dried, refilled with PBS, and stored . At 6 h, 20 microl of fluid was pipetted from each canal and placed into wells on agar plates, which were inoculated with Streptococcus sanguinis . The plates were incubated, and zones of inhibition were measured . Sampling was repeated at 24, 48, 72, 96, 120, 144, and 168 h . Residual antimicrobial activity with 2% chlorhexidine was statistically significantly superior to 5.25% NaOCl with irrigation alone and with final passive ultrasonic activation (p < 0.001) . Chlorhexidine experimental groups demonstrated residual antimicrobial activity for as long as 168 h.

J Immunol, 2003 Oct 1, 171(7), 3508 - 19
Opposing signals from pathogen-associated molecular patterns and IL-10 are critical for optimal dendritic cell induction of in vivo humoral immunity to Streptococcus pneumoniae; Colino J et al.; Interleukin10 is widely regarded as an inhibitor of immunity in part through its ability to inhibit dendritic cell (DC) function . The present study suggests a modification of this view by demonstrating instead that a critical balance exists between signals mediated by pathogen-associated molecular patterns and IL-10 for optimization of DC induction of an in vivo humoral immune response . Bone marrow-derived, CD8alpha(-) DC pulsed with Streptococcus pneumoniae in vitro induce in vivo protein- and polysaccharide-specific Ig isotype responses upon adoptive transfer into naive mice . Following bacterial activation, DC have a limited time during which they can function as effective APCs in vivo due to the onset of maturation-associated apoptosis . Autocrine IL-10, by limiting the time during which DC are responsive to widely varying levels of bacterial stimulation, delays the onset of DC apoptosis and thus prolongs the time during which DC are able to elicit in vivo humoral immunity . These data demonstrate a requirement for properly balanced positive and negative signaling in DC to optimize an in vivo immune response to a pathogen.

Infect Immun, 2003 Oct, 71(10), 6104 - 8
Identification of an inducible bacteriophage in a virulent strain of Streptococcus suis serotype 2; Harel J et al.; Streptococcus suis infection is considered to be a major problem in the swine industry worldwide . Most virulent Canadian isolates of S . suis serotype 2 do not produce the known virulence markers for this pathogen . PCR-based subtraction hybridization was adapted to isolate unique DNA sequences which were specific to virulent strains of S . suis isolated in Canada . Analysis of some subtracted DNA clones revealed significant homology with bacteriophages of gram-positive bacteria . An inducible phage (named Ss1) was observed in S . suis following the incubation of the virulent strain 89-999 with mitomycin C . Phage Ss1 has a long noncontractile tail and a small isometric nucleocapsid and is a member of the Siphoviridae family . Ss1 phage DNA appears to be present in most Canadian S . suis strains tested in this study, which were isolated from diseased pigs or had proven virulence in mouse or pig models . To our knowledge, this is the first report of the isolation of a phage in S . suis.

Infect Immun, 2003 Oct, 71(10), 6095 - 100
Streptococcus pneumoniae damages the ciliated ependyma of the brain during meningitis; Hirst RA et al.; Streptococcus pneumoniae meningitis remains a disease with a poor outcome for the patient . A region of the brain that has been neglected in the study of meningitis is the ependyma, which has been identified as a location of adult pluripotent cells . In this study we have used a rat model of meningitis to examine whether the ependymal layer is affected by S . pneumoniae . The effects included localized loss of cilia, a decrease of the overall ependymal ciliary beat frequency, and damage to the ependymal ultrastructure during meningitis . In conclusion, loss of ependymal cells and ciliary function exposes the underlying neuronal milieu to host and bacterial cytotoxins and this is likely to contribute to the neuropathology commonly observed in pneumococcal meningitis.

Infect Immun, 2003 Oct, 71(10), 6079 - 82
Streptococcus pyogenes infection in mouse skin leads to a time-dependent up-regulation of protein H expression; Smith TC et al.; Streptococcus pyogenes protein H (sph) is an immunoglobulin-binding protein present in the Mga regulon of certain M1 serotype isolates . Although sph is present in many strains, it is frequently not expressed . In this paper we show that protein H was highly expressed after bacteria were injected into the skin of mice and were recovered from the blood, kidney, or spleen at various times postinfection . The percentage of protein H-positive colonies increased with time, reaching 100% in the spleen and kidney within 24 to 72 h postinfection . The up-regulation of sph expression was also observed in a mga mutant.

Infect Immun, 2003 Oct, 71(10), 5986 - 93
Host resistance of CD18 knockout mice against systemic infection with Listeria monocytogenes; Wu H et al.; Mice with targeted mutations of CD18, the common beta2 subunit of CD11/CD18 integrins, have leukocytosis, impaired transendothelial neutrophil emigration, and reduced host defense to Streptococcus pneumoniae, a gram-positive extracellular bacterium . Previous studies using blocking monoclonal antibodies suggested roles for CD18 and CD11b in hepatic neutrophil recruitment and host innate response to Listeria monocytogenes, a gram-positive intracellular bacterium . We induced systemic listeriosis in CD18 knockout (CD18-ko) and wild-type (WT) mice by tail vein injection with Listeria . By 14 days postinjection (dpi), 8 of 10 WT mice died, compared with 2 of 10 CD18-ko mice (P < 0.01) . Quantitative organ culture showed that numbers of Listeria organisms in livers and spleens were similar in both groups at 20 min postinfection . By 3, 5, and 7 dpi, however, numbers of Listeria organisms were significantly lower in livers and spleens of CD18-ko mice than in WT mice . Histopathology showed that following Listeria infection, CD18-ko mice had milder inflammatory and necrotizing lesions in both spleens and livers than did WT mice . Cytokine assays indicated that baseline interleukin-1beta and granulocyte colony-stimulating factor (G-CSF) levels were higher in CD18-ko mice than in WT mice and that CD18-ko splenocytes produced higher levels of interleukin-1beta and G-CSF than WT splenocytes under the same amount of Listeria stimulation . These findings show that CD18 is not an absolute requirement for antilisterial innate immunity or hepatic neutrophil recruitment . We propose that the absence of CD18 in the mice results in the priming of innate immunity, as evidenced by elevated cytokine expression, and neutrophilic leukocytosis, which augments antilisterial defense.

Infect Immun, 2003 Oct, 71(10), 5633 - 9
The luxS gene of Streptococcus pyogenes regulates expression of genes that affect internalization by epithelial cells; Marouni MJ et al.; The gram-positive pathogen Streptococcus pyogenes was recently reported to possess a homologue of the luxS gene that is responsible for the production of autoinducer 2, which participates in quorum sensing of both gram-positive and gram-negative bacteria . To test the effect of LuxS on streptococcal internalization, a LuxS mutant was constructed in strain SP268, an invasive M3 serotype . Functional analysis of the mutant revealed that it was internalized by HEp-2 cells with higher efficiency than the wild type (wt) . Several genes, including hasA (hyaluronic acid synthesis), speB (streptococcal pyrogenic exotoxin B), and csrR (capsule synthesis regulator), a part of a two-component regulatory system, are known to affect the internalization of strain SP268 (J . Jadoun, O . Eyal, and S . Sela, Infect . Immun . 70:462-469, 2002) . Therefore, the expression of these genes in the mutant and in the wt was examined . LuxS mutation significantly reduced the mRNA level of speB and increased the mRNA level of emm3 . No substantial effect was observed on transcription of hasA and csrR . Yet less hyaluronic acid capsule was expressed in the mutant . Further analysis revealed that luxS is under the regulation of the two-component global regulator CsrR . Our results indicate that LuxS activity in strain SP268 plays an important role in the expression of virulence factors associated with epithelial cell internalization.

Infect Immun, 2003 Oct, 71(10), 5541 - 8
Pneumococcal lipoteichoic acid (LTA) is not as potent as staphylococcal LTA in stimulating Toll-like receptor 2; Han SH et al.; Streptococcus pneumoniae is a leading cause of gram-positive sepsis, and lipoteichoic acid (LTA) may be important in causing gram-positive bacterial septic shock . Even though pneumococcal LTA is structurally distinct from the LTA of other gram-positive bacteria, the immunological properties of pneumococcal LTA have not been well characterized . We have investigated the ability of LTAs to stimulate human monocytes by using highly pure and structurally intact preparations of pneumococcal LTA and its two structural variants . The variants were pneumococcal LTA with only one acyl chain (LTA-1) and completely deacylated LTA (LTA-0) . The target cells used in the study were peripheral blood mononuclear cells (PBMCs) and two model cell lines (CHO/CD14/TLR2 and CHO/CD14/TLR4) that express human CD25 protein in response to Toll-like receptor 2 (TLR2) and TLR4 stimulation, respectively . Intact pneumococcal LTA and LTA-1 stimulated PBMC and CHO/CD14/TLR2 cells in a dose-dependent manner but did not stimulate CHO/CD14/TLR4 cells . Pneumococcal LTA was about 100-fold less potent than Staphylococcus aureus LTA in stimulating the CHO/CD14/TLR2 cells and PBMCs . LTA-0 (or pneumococcal teichoic acid) stimulated neither CHO/CD14/TLR2 nor CHO/CD14/TLR4 cells even at high concentrations . Excess teichoic acid, LTA-0, antibodies to phosphocholine, or antibodies to TLR4 did not inhibit the LTA-induced TLR2 stimulation . However, antibodies to CD14, TLR1, or TLR2 suppressed tumor necrosis factor alpha (TNF-alpha) production by PBMCs in response to LTA or LTA-1 . These results suggest that pneumococcal LTA with one or both acyl chains stimulates PBMCs primarily via TLR2 with the help of CD14 and TLR1.

Infect Immun, 2003 Oct, 71(10), 5531 - 40
Differential expression of cytokine genes and inducible nitric oxide synthase induced by opacity phenotype variants of Streptococcus pneumoniae during acute otitis media in the rat; Long JP et al.; Phase variation in the colonial opacity phenotype of Streptococcus pneumoniae has been implicated as a factor in bacterial adherence, colonization, and invasion in the pathogenesis of pneumococcal otitis media (OM) . The purpose of this study was to determine whether S . pneumoniae opacity variants influence the induction of gene expression for proinflammatory mediators in vivo using the rat model of OM . Both the opaque and transparent phenotype variants induced a significant up-regulation in gene expression for interleukin-1alpha (IL-1alpha), IL-1beta, IL-6, IL-10, tumor necrosis factor alpha, and inducible nitric oxide synthase (iNOS) compared to saline sham-inoculated controls at both 4 and 24 h postinoculation (P < 0.05 in all cases) . Furthermore, whereas a significant difference in gene expression was evident for only IL-6 (greater following challenge with the opaque variant) and IL-1beta (greater following challenge with the transparent variant) at 4 h, by 24 h the opaque variant cohort demonstrated a significant increase in gene expression for IL-1alpha, IL-1beta, IL-6, IL-10, and iNOS relative to animals inoculated with the transparent phenotype variant (P < 0.05 in all cases) . Enzyme-linked immunosorbent assay results confirmed the gene expression data as determined by real-time PCR . Moreover, the concentrations of the opaque variant in the middle ear lavage fluid were a full log higher than those of the transparent variant . The aforementioned results indicate that the opaque phenotype variant is more efficient at survival and multiplication within the middle ear space, resulting in the accumulation of more inflammatory cells and the enhanced expression and production of inflammatory mediators . However, when the data were normalized to account for differences in middle ear bacterial titers, it became apparent that the transparent variant of S . pneumoniae is a more potent inducer of inflammation, triggering the accumulation of more inflammatory cells and substantially greater fold increases in the expression and production of inflammatory mediators . Data from this study indicate that S . pneumoniae opacity variants influence the temporal mRNA expression of inflammatory mediators within the middle ear.

Arch Dis Child, 2003 Oct, 88(10), 859 - 61
How many episodes of hospital care might be prevented by widespread uptake of pneumococcal conjugate vaccine?
McIntosh ED.
BACKGROUND: It is likely that disease specific infectious morbidity is under-reported . Microbiologically identifiable diseases may be "hidden" in ICD-10 code as "unspecified" disease . AIMS: To estimate the proportion of "unspecified" morbidity of infectious cause in infants and young children reported by Hospital Episode Statistics (HES) in England in 1999 that could reasonably be attributed to Streptococcus pneumoniae, and to calculate what number and proportion of diseases could potentially be prevented by a programme of pneumococcal conjugate vaccination . METHODS: Proportions of HES "unspecified" septicaemia, meningitis, and pneumonia attributable to pneumococcal infection were estimated by applying theoretical rates obtained from studies using highly sensitive diagnostic tests . The numbers obtained were added to those coded as pneumococcal in origin . The vaccine preventable proportion was then calculated using serogroup coverage, disease specific efficacy, and vaccine uptake . RESULTS: For infants and children 3 months to 5 years of age in 1999, HES reported 134, 245, and 216 episodes of pneumococcal septicaemia, meningitis, and pneumonia respectively . In addition, 68, 36, and 2548 episodes of "unspecified" disease respectively are probably pneumococcal in origin . For hospitalisations in England in this age group, 157/202 (78%) cases of pneumococcal septicaemia, 218/281 (76%) cases of pneumococcal meningitis, and 452/2764 (16%) cases of pneumococcal pneumonia may be preventable annually by means of pneumococcal conjugate vaccination . CONCLUSIONS: Paediatric hospital morbidity in England due to pneumococcal septicaemia, meningitis, and pneumonia is under-reported by 34%, 13% and 92% respectively . A larger proportion of morbidity is preventable than implied by ICD-10 code alone.

J Microbiol Methods, 2003 Oct, 55(1), 29 - 34
Inhibition of fibronectin binding of some bacterial cells by subtle pH increase within the physiological range; Ito HO et al.; The fibronectin (Fn)-binding ability of microorganisms is considered to be involved in their pathogenicities . Granulicatella adiacens, a member of the oral flora and a causative agent of culture-negative infective endocarditis, showed nearly maximum binding to immobilized Fn at pH 7.2 but greatly reduced binding at a slightly higher pH 7.4 and almost no binding at pH 7.6 in the presence of physiological concentration of NaCl (0.15 M) . A similar pH-sensitive Fn-binding property was noted with Escherichia coli and Abiotrophia defectiva, but not with Streptococcus pyogenes nor Staphylococcus aureus . In contrast, bindings to laminin and fibrinogen observed for some of these strains were unaffected by the same pH changes . This fastidious pH-dependency of Fn-binding abilities of some bacteria warns that the pH condition must be seriously considered in the in vitro assay of bacterial adherence to fibronectin.

J Biol Chem, 2003 Nov 28, 278(48), 48178 - 87 Epub 2003 Sep 17.
The human polymeric immunoglobulin receptor binds to Streptococcus pneumoniae via domains 3 and 4; Lu L et al.; Streptococcus pneumoniae (the pneumococcus) is a major cause of bacterial pneumonia, middle ear infection (otitis media), sepsis, and meningitis . Our previous study demonstrated that the choline-binding protein A (CbpA) of S . pneumoniae binds to the human polymeric immunoglobulin receptor (pIgR) and enhances pneumococcal adhesion to and invasion of cultured epithelial cells . In this study, we sought to determine the CbpA-binding motif on pIgR by deletional analysis . The extra-cellular portion of pIgR consists of five Ig-like domains (D1-D5), each of which contains 104-114 amino acids and two disulfide bonds . Deletional analysis of human pIgR revealed that the lack of either D3 or D4 resulted in the loss of CbpA binding, whereas complete deletions of domains D1, D2, and D5 had undetectable impacts . Subsequent analysis showed that domains D3 and D4 together were necessary and sufficient for the ligand-binding activity . Furthermore, CbpA binding of pIgR did not appear to require Ca2+ or Mg2+ . Finally, treating pIgR with a reducing agent abolished CbpA binding, suggesting that disulfide bonding is required for the formation of CbpA-binding motif(s) . These results strongly suggest a conformational CbpA-binding motif(s) in the D3/D4 region of human pIgR, which is functionally separated from the IgA-binding site(s).

Curr Infect Dis Rep, 2003 Oct, 5(5), 407 - 415
Necrotizing Soft Tissue Infections; File TM; Necrotizing soft tissue infections are characterized by necrosis of skin and associated structures . Despite advances in the diagnosis and treatment of these infections, the mortality remains high . There have been increasing reports of necrotizing fasciitis caused by group A Streptococcus over the past decade . Recent information supports the role of superantigens in the pathogenesis of this infection . The approach to management requires expeditious evaluation with early surgery and appropriate antimicrobial agents . Limited data suggest that surgical debridement may be delayed in selected patients until the patient is stable by the use of intravenous immunoglobulin, which can neutralize superantigens.

J Womens Health (Larchmt), 2003 Jul-Aug, 12(6), 527 - 32
Report from the CDC . Awareness of perinatal group B streptococcal infection among women of childbearing age in the United States, 1999 and 2002; Cowgill K et al.; BACKGROUND: The issuance in 2002 of new guidelines recommending universal screening for group B Streptococcus (GBS), a leading cause of neonatal sepsis in the United States, has created a new opportunity to educate women of childbearing age to be active partners in prevention . METHODS: To assess baseline levels of awareness about perinatal GBS, we analyzed responses to a question included in a health communications/social marketing survey in 1999 and 2002 . RESULTS: Among the 2917 women under 50 who responded, 47% reported ever having heard of perinatal GBS . Among women pregnant at the time of the survey, awareness was 66% . Women with a high school education or less (OR = 0.60, 95% CI 0.50-0.73), household income <25,000 US dollars (OR 0.65, 95% CI 0.54-0.79), or reporting black, Asian/Pacific Islander, or other race (ORs {95% CI} 0.70 {0.57-0.87}, 0.61 {0.41-0.90}, 0.41 {0.20-0.85}, respectively) had lower awareness of perinatal GBS than other women . Women currently pregnant (OR 2.2, 95% CI 1.5-3.3) had higher awareness . CONCLUSIONS: Awareness of perinatal GBS is high among currently pregnant women, for whom this issue is most important . Efforts to raise awareness should be targeted to women from traditionally underserved populations, such as those who are of nonwhite race or who have lower educational attainment or household income.

Curr Med Res Opin, 2003, 19(5), 421 - 9
Comparison of 5 days of extended-release clarithromycin versus 10 days of penicillin V for the treatment of streptococcal pharyngitis/tonsillitis: results of a multicenter, double-blind, randomized study in adolescent and adult patients; Takker U et al.; OBJECTIVE: This study compared a short-course of clarithromycin with a standard course of penicillin V in patients with tonsillopharyngitis caused by Streptococcus pyogenes . Research design and methods: A total of 539 patients, aged 12-75 years, were randomized to receive either clarithromycin extended-release (ER) 500 mg once daily for 5 days or penicillin V 500 mg three times daily for 10 days in this multicenter, double-blind, parallel-group trial . Eligibility required a positive antigen test for group A beta-hemolytic streptococcus (GABHS) followed by confirmatory culture . MAIN OUTCOME MEASURES: Bacteriological and clinical assessments were conducted at each study visit (visit 1: study day 1; visit 2: study day 3; visit 3: study days 8-12; visit 4: study days 13-20; and visit 5: study days 40-50) . RESULTS: At the test-of-cure visit (visit 3 for clarithromycin ER patients and visit 4 for penicillin V patients) in per-protocol patients, 5 days of clarithromycin ER was comparable to 10 days of penicillin V in eradicating S . pyogenes (89% (157/177) vs 90% (139/154) respectively; 95% CI for difference (-8.2, 5.1)) . Bacterial eradication was sustained in both treatment groups at the follow-up visit (88% (135/153) vs 91% (112/123) respectively; 95% CI for difference (-10.0, 4.4)) . Clinical cure was achieved in > or = 94% of patients in each treatment group . The most commonly reported study drug-related adverse events (< or = 3% in either treatment group) were abdominal pain, diarrhea, dyspepsia and nausea . CONCLUSION: Clarithromycin ER 500 mg once daily for 5 days is equally effective as penicillin V 500 mg three times daily for 10 days in the treatment of adolescent and adult patients with streptococcal tonsillopharyngitis.

J Bacteriol, 2003 Oct, 185(19), 5791 - 9
Control of enzyme IIscr and sucrose-6-phosphate hydrolase activities in Streptococcus mutans by transcriptional repressor ScrR binding to the cis-active determinants of the scr regulon; Wang B et al.; In Streptococcus mutans, enzyme II(scr) and sucrose-6-phosphate hydrolase are two important enzymes in the transport and metabolism of dietary sucrose . The scr regulon of S . mutans is composed of three genes, scrA and scrB, which code for enzyme II(scr) and sucrose-6-phosphate hydrolase, respectively, and scrR, which codes for a GalR-LacI-type transcription regulator . It was previously shown that expression of both scrA and scrB is similarly induced by sucrose . Mutation in the scrR gene resulted in increased expression of scrB relative to that in the wild-type strain . In this study, we employed DNA mobility shift and DNase I protection assays with a purified ScrR-histidine tag fusion protein to examine the DNA binding properties of ScrR to the promoter regions of the scrA and scrB genes . The results showed that ScrR bound specifically to the promoter regions of both scrA and scrB . Two regions with high affinity for ScrR in the promoter sequences of the scrA and scrB genes were identified by DNase I protection assays . One, O(C), which includes a 20-bp imperfect inverted-repeat sequence, is located between the two promoters, and the other, O(B), is located within the scrB promoter region containing a 37-bp imperfect direct-repeat sequence . Mutations of O(B) and O(C) resulted in constitutive transcription and expression of both the scrA and scrB genes . Our results indicated that S . mutans coordinates the activities of enzyme II(scr) and sucrose-6-phosphate hydrolase by transcriptional repressor ScrR binding to the promoter regions of the scr regulon.

J Biol Chem, 2003 Nov 21, 278(47), 46649 - 53 Epub 2003 Sep 16.
Presence of D-alanine in an endopeptidase from Streptococcus pyogenes; Lee SG et al.; D-amino acids are commonly found in peptide antibiotics and the cell wall peptidoglycan of bacterial cell walls but have not been identified in proteins or enzymes . Here we report the presence of 6-7 A-alanine residues in an endopeptidase of Streptococcus pyogenes, a unique enzyme involved in surface protein attachment that we term LPXTGase . Using D-amino acid oxidase coupled with catalase for the deamination of D-alanine to pyruvic acid (a conversion unique to D-alanine), we were able to identify {14C}pyruvic acid in a {14C}alanine-labeled preparation of purified LPXTGase, which represents 27% of the amino acid composition . Because D-amino acids are not accommodated in ribosomal peptide synthesis, these results suggest that the same process used in assembling peptide antibiotics or a yet unidentified mechanism may synthesize the core protein of this endopeptidase.

BMC Neurosci . 2003 Sep 16;4(1):21.
Blockade of NMDA receptor subtype NR2B prevents seizures but not apoptosis of dentate gyrus neurons in bacterial meningitis in infant rats; Kolarova A et al.; BACKGROUND: Excitotoxic neuronal injury by action of the glutamate receptors of the N-methyl-d-aspartate (NMDA) subtype have been implicated in the pathogenesis of brain damage as a consequence of bacterial meningitis . The most potent and selective blocker of NMDA receptors containing the NR2B subunit is (R,S)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperid inepropanol (RO 25-6981) . Here we evaluated the effect of RO 25-6981 on hippocampal neuronal apoptosis in an infant rat model of meningitis due to Streptococcus pneumoniae . Animals were randomized for treatment with RO 25-6981 at a dosage of either 0.375 mg (15 mg/kg; n = 28) or 3.75 mg (150 mg/kg; n = 15) every 3 h or an equal volume of sterile saline (250 microl; n = 40) starting at 12 h after infection . Eighteen hours after infection, animals were assessed clinically and seizures were observed for a period of 2 h . At 24 h after infection animals were sacrificed and brains were examined for apoptotic injury to the dentate granule cell layer of the hippocampus . RESULTS: Treatment with RO 25-6981 had no effect on clinical scores, but the incidence of seizures was reduced (P < 0.05 for all RO 25-6981 treated animals combined) . The extent of apoptosis was not affected by low or high doses of RO 25-6981 . Number of apoptotic cells (median {range}) was 12.76 {3.16-25.3} in animals treated with low dose RO 25-6981 (control animals 13.8 {2.60-31.8}; (P = NS) and 9.8 {1.7-27.3} (controls: 10.5 {2.4-21.75}) in animals treated with high dose RO 25-6981 (P = NS) . CONCLUSIONS: Treatment with a highly selective blocker of NMDA receptors containing the NR2B subunit failed to protect hippocampal neurons from injury in this model of pneumococcal meningitis, while it had some beneficial effect on the incidence of seizures.

BMC Biotechnol . 2003 Sep 17;3(1):15.
In vivo mucosal delivery of bioactive human interleukin 1 receptor antagonist produced by Streptococcus gordonii; Ricci S et al.; BACKGROUND: Interleukin-1 (IL-1) is a cytokine involved in the initiation and amplification of the defence response in infectious and inflammatory diseases . IL-1 receptor antagonist (IL-1ra) is an inactive member of the IL-1 family and represents one of the most potent mechanisms for controlling IL-1-dependent inflammation . IL-1ra has proven effective in the therapy of acute and chronic inflammatory diseases in experimental animal models and also in preliminary clinical trials . However, optimisation of therapeutic schedules is still needed . For instance, the use of drug delivery systems targeting specific mucosal sites may be useful to improve topical bioavailability and avoid side effects associated with systemic administration . RESULTS: In order to develop systems for the delivery of IL-1ra to mucosal target sites, a Streptococcus gordonii strain secreting human IL-1ra was constructed . The recombinant IL-1ra produced by S . gordonii was composed of the four amino acid residues RVFP of the fusion partner at the N-terminus, followed by the mature human IL-1ra protein . RFVP/IL-1ra displayed full biological activity in vitro in assays of inhibition of IL-1beta-induced lymphocyte proliferation and was released by recombinant S . gordonii in vivo both at the vaginal and the gastrointestinal mucosa of mice . RFVP/IL-1ra appeared beneficial in the model of ulcerative colitis represented by IL-2-/- mice (knock-out for the interleukin-2 gene), as shown by the body weight increase of IL-2-/- mice locally treated with S . gordonii producing RFVP/IL-1ra . CONCLUSIONS: These results indicate that recombinant S . gordonii can be successfully used as a delivery system for the selective targeting of mucosal surfaces with therapeutic proteins.

Clin Exp Immunol, 2003 Oct, 134(1), 23 - 31
Differential activation of the immune system by virulent Streptococcus pneumoniae strains determines recovery or death of the host; Mizrachi-Nebenzahl Y et al.; Streptococcus pneumoniae infection may result in asymptomatic carriage, mucosal or invasive disease . We hypothesize that self-limiting or fatal disease outcome follows infection with S . pneumoniae differential activation of the host immune response . BALB/c and C57BL/6 mice were inoculated intranasally with S . pneumoniae serotype 3 strain WU2 and serotype 14 strain DW14 and mortality, bacterial load, pathological changes in the lungs and cytokines mRNA levels in the spleen were analysed . No differences between the C57BL/6 and the BALB/c inbred mice were observed except for the severity of their lung pathology and IL-4 expression . Infection of the two mouse strains with S . pneumoniae WU2 resulted in sepsis and death that occurred within 4 days post-inoculation . This death was preceded, in both mouse strains, in an increase over time of the lung bacterial load and bacteraemia . The lung pathology was characterized by diffuse pneumonia with marked congestion of the lungs . Analysis of mRNA expression of cytokines in the spleen revealed no alterations in tumour necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, interleukin (IL)-12 and interferon (IFN)-gamma and induction of IL-10 and IL-4 . The two strains of mice survived infection with S . pneumoniae DW14 . This was accompanied by a reduction over time of lung bacterial load and bacteraemia . The lung pathology was characterized by focal lymphocyte infiltration and preserved architecture of the organ . Analysis of mRNA expression of cytokines in the spleen revealed a significant decrease in the levels of TNF-alpha, TGF-beta, IL-12 and IFN-gamma mRNA expression, which usually precedes cytokine protein expression . Interestingly, a significant increase in the levels of IL-4 mRNA expression was found in BALB/c mice only . This study suggests that differential activation or evasion of cytokine expression by S . pneumoniae virulent strains determines disease outcome regardless of the host's immunogenetic background.

Vet Rec, 2003 Aug 30, 153(9), 264 - 8
Verrucous endocarditis associated with Streptococcus bovis in mink (Mustela vison); Pedersen K et al.; Between 1998 and 2001, mortalities due to verrucous endocarditis were experienced at several mink farms . Gram-positive cocci were isolated from the endocardium of all the animals examined but not always from other internal organs . Almost all the isolates were identified as Streptococcus bovis and only a few isolates belonged to other Streptococcus species . Typing by pulsed-field gel electrophoresis of a selection of isolates revealed several patterns and several different clones . Attempts to reproduce disease by the injection of cultures of a field isolate into healthy mink failed.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2003 Sep, 96(3), 332 - 9
Bacteriological study of root canals associated with periapical abscesses; de Sousa EL et al.; OBJECTIVE: The aim of this study was to identify microorganisms from root canals with periapical abscesses and to ascertain the susceptibility of Peptostreptococcus prevotii and Fusobacterium necrophorum to antimicrobials.Study design Thirty root canals were microbiologically sampled by using sterile paper points . The concomitant microorganisms were identified through the use of established methods . The susceptibility of P prevotii and F necrophorum to antimicrobials was evaluated by using the E test method . RESULTS: A total of 117 different bacterial strains were recovered, including 75 strict anaerobes or microphilic species . The most frequently isolated strict anaerobes were P prevotii, Peptostreptococcus micros, and F necrophorum . Facultative bacteria such as Gemella morbillorum and Streptococcus mitis were also found, albeit less frequently . The data revealed that P prevotii and F necrophorum were susceptible to the tested antibiotics . CONCLUSIONS: Gram-positive anaerobic bacteria predominate in the mixed microbiota of root canals with periapical abscesses . Moreover, P prevotii and F necrophorum are susceptible to the tested antibiotics.

Pediatr Emerg Care, 2003 Aug, 19(4), 226 - 30
Notifying emergency department patients of negative test results: pitfalls of passive communication; Keren R et al.; OBJECTIVE: Many emergency departments that perform a high volume of group A Streptococcus throat cultures inform patients or parents that unless they are notified of a positive result they can assume that their throat culture result is negative . Thus, positive throat culture results are communicated actively and negative results are communicated passively . We sought to determine the effectiveness and safety of such a system . METHODS: Prospective cohort study of 301 consecutive patients who had group A Streptococcus throat cultures obtained between March 28, 2000, and May 10, 2000, in the emergency department of an urban, academic, tertiary-care children's hospital . Outcomes were determined by telephone surveys of patients or their parents or guardians . The primary outcome was whether respondents had accurate knowledge of the throat culture result . Secondary outcomes included receipt of appropriate treatment instructions, need for another telephone call to the emergency department or primary-care provider to clarify the result or treatment instructions, satisfaction with the communication process, and preference to receive both positive and negative results or just positive results . RESULTS: Fifty-three percent of respondents did not have accurate knowledge of the throat culture result, 5% received inappropriate treatment instructions, 13% sought further clarification, 29% were dissatisfied with the communication process, and 85% preferred to receive both positive and negative results . Parents of patients with positive results were more likely to have accurate knowledge of the result (odds ratio 6.9, 95% confidence interval 1.4-65.7) and to be satisfied with the communication process . CONCLUSIONS: Passive communication of negative throat culture results to patients seen in the emergency department can be unreliable . Active communication of both positive and negative results may improve patient knowledge and satisfaction and ensure appropriate therapy, but in the absence of automated notification systems, would be resource intensive.

J Med Microbiol, 2003 Oct, 52(Pt 10), 903 - 8
Geographical difference of disease association in Streptococcus bovis bacteraemia; Lee RA et al.; From 1996 to 2001, 48 Streptococcus bovis strains were isolated from blood cultures of 37 patients in one hospital . Median patient age was 68 years (range: 1 day-88 years) . The male : female ratio was 23 : 14 . Most patients (97 %) had underlying diseases, including biliary tract disease in 14 (38 %), diabetes mellitus in 12 (32 %), liver parenchymal disease in seven (19 %), carcinoma of the colon in four (11 %) and other malignancies in four (11 %) . No infective foci (indicative of primary bacteraemia) were identified in 15 patients (40 %) and 14 (38 %) had acute cholangitis/cholecystitis, but only four (11 %) had infective endocarditis . Two (5 %), three (8 %) and 32 (87 %) patients had S . bovis of biotypes I, II/1 and II/2, respectively, and three (8 %), two (5 %) and 32 (87 %) patients had S . bovis of genotypes 1, 2a and 2b, respectively . All isolates were sensitive to penicillin, cephalothin and vancomycin, 24 (65 %) were resistant to erythromycin and 15 (41 %) were resistant to clindamycin (these strains were also resistant to erythromycin) . Thirteen isolates that were erythromycin- and clindamycin-resistant possessed the ermB gene, 10 possessed the ermT gene and one possessed both the ermB and ermT genes . Overall, seven patients (19 %) died . In contrast to most other reports from western countries, where carcinoma of the colon and infective endocarditis were the major underlying disease and infective focus associated with S . bovis bacteraemia, biliary tract disease and acute cholangitis and/or cholecystitis were the major underlying diseases associated with S . bovis bacteraemia in our locality.

Southeast Asian J Trop Med Public Health, 2003 Mar, 34(1), 154 - 8
Streptococcus suis infection: clinical features and diagnostic pitfalls; Donsakul K et al.; Eight cases of Streptococcus suis (S . suis) infection between 1993-1999 were retrospectively studied . There were 6 cases of meningitis and 2 cases of endocarditis . Acute meningitis with early sensorineural hearing loss was the characteristic feature and the most common presentation of S . suis infection . S . suis endocarditis is a rare presentation in Thailand . This organism was often mistaken for Streptococcus pneumoniae or Streptococcus viridans . In this study, this was true in five cases in whom S . suis was identified later . However, the rapid diagnosis of S . suis meningitis may rely on Gram stain of the CSF in the setting of acute meningitis with hearing loss . These cases were treated with intravenous penicillin or ampicillin with a mean duration of 4 weeks . This treatment was very effective and there was no relapse among these patients.

EMBO J, 2003 Sep 15, 22(18), 4856 - 65
A novel sensor of NADH/NAD+ redox poise in Streptomyces coelicolor A3(2); Brekasis D et al.; We describe the identification of Rex, a novel redox-sensing repressor that appears to be widespread among Gram-positive bacteria . In Streptomyces coelicolor Rex binds to operator (ROP) sites located upstream of several respiratory genes, including the cydABCD and rex-hemACD operons . The DNA-binding activity of Rex appears to be controlled by the redox poise of the NADH/NAD+ pool . Using electromobility shift and surface plasmon resonance assays we show that NADH, but not NAD+, inhibits the DNA-binding activity of Rex . However, NAD+ competes with NADH for Rex binding, allowing Rex to sense redox poise over a range of NAD(H) concentrations . Rex is predicted to include a pyridine nucleotide-binding domain (Rossmann fold), and residues that might play key structural and nucleotide binding roles are highly conserved . In support of this, the central glycine in the signature motif (GlyXGlyXXGly) is shown to be essential for redox sensing . Rex homologues exist in most Gram-positive bacteria, including human pathogens such as Staphylococcus aureus, Listeria monocytogenes and Streptococcus pneumoniae.

J Immunol Methods, 2003 Aug, 279(1-2), 101 - 10
A highly sensitive immuno-PCR assay for detecting Group A Streptococcus; Liang H et al.; A highly sensitive hybrid assay, based on immuno polymerase chain reaction (immuno-PCR) and enzyme-linked immunosorbent assay (ELISA) techniques, was developed for the detection of pathogenic Group A Streptococcus (Strep A) . Cells were disrupted by sonication and then coated onto the walls of Maxisorp microtiter plates . Next, biotinylated anti-Group A monoclonal antibody (mAb) was bound to the antigen and then linked, via a streptavidin (STV) bridge, to biotinylated reporter DNA . After extensive washing, the denatured reporter DNA was transferred to PCR tubes, amplified, electrophoresed, and used as the signal for detection of bacteria . The minimum detection limit of this assay is the equivalent of approximately one one-thousandth of a Streptococcus pyogenes cell, even in the presence of 100,000 Escherichia coli cells . The combination of multiple antigens per cell and PCR amplification provides the extreme sensitivity in this immuno-PCR assay . No cross-reaction was found with other Streptococcus species . We also directly linked the anti-Group A monoclonal antibody to DNA using succinimidyl 4-{N-maleimidomethyl}-cyclohexane-1-carboxylate (SMCC) . The sensitivity using directly linked antibody-reporter DNA was approximately 10 cells . Because this assay could be adapted for detection of many different bacteria in a variety of sample types, we tested the potential for interference from substances that could be present in clinical, food, and environmental samples . Sonicated meat or human plasma did not inhibit detection; however, extracts of concentrated soil samples were somewhat inhibitory . This highly specific, sensitive, and robust assay could be applied to clinical detection of Group A Streptococcus and serves as a model for other immuno-PCR assays.

J Appl Microbiol, 2003, 95(4), 787 - 98
Microarray analysis of erythromycin resistance determinants; Volokhov D et al.; AIMS: To develop a DNA microarray for analysis of genes encoding resistance determinants to erythromycin and the related macrolide, lincosamide and streptogramin B (MLS) compounds . METHODS AND RESULTS: We developed an oligonucleotide microarray containing seven oligonucleotide probes (oligoprobes) for each of the six genes (ermA, ermB, ermC, ereA, ereB and msrA/B) that account for more than 98% of MLS resistance in Staphylococcus aureus clinical isolates . The microarray was used to test reference and clinical S . aureus and Streptococcus pyrogenes strains . Target genes from clinical strains were amplified and fluorescently labelled using multiplex PCR target amplification . The microarray assay correctly identified the MLS resistance genes in the reference strains and clinical isolates of S . aureus, and the results were confirmed by direct DNA sequence analysis . Of 18 S . aureus clinical strains tested, 11 isolates carry MLS determinants . One gene (ermC) was found in all 11 clinical isolates tested, and two others, ermA and msrA/B, were found in five or more isolates . Indeed, eight (72%) of 11 clinical isolate strains contained two or three MLS resistance genes, in one of the three combinations (ermA with ermC, ermC with msrA/B, ermA with ermC and msrA/B) . CONCLUSIONS: Oligonucleotide microarray can detect and identify the six MLS resistance determinants analysed in this study . SIGNIFICANCE AND IMPACT OF THE STUDY: Our results suggest that microarray-based detection of microbial antibiotic resistance genes might be a useful tool for identifying antibiotic resistance determinants in a wide range of bacterial strains, given the high homology among microbial MLS resistance genes.

Jpn J Ophthalmol, 2003 Sep-Oct, 47(5), 512 - 8
Six cases of bacterial infection in porous orbital implants; You JR et al.; BACKGROUND: We present 6 cases of bacterial infection that developed after porous orbital implant surgery . CASES: Five patients with hydroxyapatite implants showed lid swelling, discharge, and suppurative granuloma 14 days to 3 years after surgery . The hydroxyapatite implants were removed 14 days to 41 months postoperatively, and synthetic porous polyethylene orbital implants were inserted . Thick discharge and conjunctival melting was noted 14 months after primary Medpor implant surgery in the sixth patient, and the infection was controlled by medical therapy . OBSERVATIONS: The culture of specimens removed with swabs from the conjunctiva of patients and from the hydroxyapatite implants showed growth of Staphylococcus aureus, Staphylococcus epidermidis, alpha-hemolytic streptococcus and peptostreptococcus in 4 patients, whereas Streptococcus pyogenes were cultured from the conjunctiva in the Medpor implant patient . Culture for the remaining patient was negative .CONCLUSIONS: If there is continuous pain, injection, and discharge after porous implant insertion, bacterial infection in the implant should be considered immediately . Systemic antibiotics and topical eye drops should be administered without delay . If no improvement is observed, the implant should be removed and a different approach must be considered.

Emerg Infect Dis, 2003 Aug, 9(8), 970 - 7
Invasive group A streptococcal disease: risk factors for adults; Factor SH; We conducted a case-control study to identify risk factors for invasive group A streptococcal (GAS) infections, which can be fatal . Case-patients were identified when Streptococcus pyogenes was isolated from a normally sterile site and control subjects (two or more) were identified and matched to case-patients by using sequential-digit telephone dialing . All participants were noninstitutionalized surveillance area residents, >18 years of age . Conditional logistic regression identified the risk factors for invasive GAS infection: in adults 18 to 44 years of age, exposure to one or more children with sore throats (relative risk {RR}=4.93, p=0.02), HIV infection (RR=15.01, p=0.04), and history of injecting drug use (RR=14.71, p=0.003); in adults >45 years of age, number of persons in the home (RR=2.68, p=0.004), diabetes (RR=2.27, p=0.03), cardiac disease (RR=3.24, p=0.006), cancer (RR=3.54, p=0.006), and corticosteroid use (RR=5.18, p=0.03) . Thus, host and environmental factors increased the risk for invasive GAS disease.

Arch Pharm Res, 2003 Aug, 26(8), 638 - 43
Antimicrobial resistance patterns of vancomycin-resistant Streptococcus equinus isolated from animal foods and epidemiological typing of resistant S . equinus by microbial uniprimer kit; Choi SS et al.; Raw milk samples, and cow and chicken intestines were tested to isolate vancomycin-resistant, gram-positive bacteria . From these samples, we isolated seven vancomycin-resistant Streptococcus equinus, two vancomycin-resistant viridans Streptococcus and two vancomycin-resistant Enterococcus faecium . The MICs of several antibiotics, including vancomycin, against these strains were tested . Seven isolates of S . equinus showed high level resistance to vancomycin and teicoplanin (>100 microg/mL) . The cell wall thickness of these strains was compared with that of the sensitive strain by TEM and no differences were obserbed between these strains . We compared the strains of vancomycin-resistant Streptococcus equinus using PCR with Microbial Uniprimer Kit . We concluded that it is necessary to combine other methods in order to cluster and identify all isolates of S . equinus.

Clin Diagn Lab Immunol, 2003 Sep, 10(5), 886 - 90
Group A streptococcal antibodies in subjects with or without rheumatic fever in areas with high or low incidences of rheumatic fever; Ayoub EM et al.; The levels of streptococcal antibody titers in populations with or without rheumatic fever from an area with a relatively high incidence of rheumatic fever and an area with a low incidence of this disease were compared . Streptococcal antibody titers were determined for two populations, each of which included children without rheumatic fever (nonrheumatic children) and rheumatic fever patients . The two populations were derived from two separate geographic areas, one with a high incidence of rheumatic fever (Grenada) and another with a low incidence of this disease (central Florida) . The results revealed an absence of consistent differences in the geometric mean antibody titers between the nonrheumatic subjects and the rheumatic fever patients from Grenada . In the population from Grenada, the mean anti-streptolysin O and anti-DNase B titers were higher in the nonrheumatic controls (P of 0.085 and 0.029, respectively) . However, the mean titer of the antibody to the group A streptococcal cell wall carbohydrate was higher in the rheumatic fever patients than in the nonrheumatic controls (P = 0.047) . This finding contrasted with the finding that the means of all three streptococcal antibody titers in the patients with rheumatic fever were significantly higher than those in the nonrheumatic subjects from Florida (P = 0.01-<0.001) . The reason for this paradoxical finding became evident when the streptococcal antibody titers of the nonrheumatic subjects from Grenada and Florida were compared, revealing significantly higher levels of all three antibodies in the nonrheumatic subjects from Grenada than in the nonrheumatic subjects from Florida (P < 0.001) . These results suggest that nonrheumatic individuals in an area with a high incidence of rheumatic fever have inordinately elevated levels of streptococcal antibodies in serum . The presence of elevated streptococcal antibody titers in such a population, which probably reflects a high background prevalence of streptococcal infections, should be taken into consideration when evaluating the role of the group A streptococcus in nonpurulent complications of infections.

J Infect Dis, 2003 Sep 15, 188(6), 818 - 27 Epub 2003 Sep 04.
Molecular genetic analysis of 675 group A streptococcus isolates collected in a carrier study at Lackland Air Force Base, San Antonio, Texas; Hoe NP et al.; Contemporary molecular genetic analysis methods have not been used to study large samples of carriage isolates of group A Streptococcus . To determine the emm types causing asymptomatic carriage and pharyngitis in a closed population, we analyzed 675 isolates recovered from a population-based surveillance study of 10,634 recruits at Lackland Air Force Base, Texas, during 4 months in 1993-1994 . Strains with emm1 and emm6 alleles accounted for only 22% of the isolates recovered from asymptomatic recruits at entrance to training . However, these 2 emm types caused 69% of the pharyngitis cases identified during training and represented 51% of the isolates recovered from the throat on exit from training . Sequence analysis of the hypervariable sic gene documented that distinct emm1 subclones disseminated in specific training groups called flights . The preferential increase in the prevalence of emm1 and emm6 isolates during the 6-week training period indicates an enhanced ability of these strains to disseminate and cause disease in this population.

Am J Rhinol, 2003 Jul-Aug, 17(4), 209 - 14
Nasopharyngeal reservoir of bacterial otitis media and sinusitis pathogens in adults during wellness and viral respiratory illness; Chi DH et al.; BACKGROUND: The carriage rate of pathogenic bacteria in the nasopharynx (NP) was determined using three separate techniques for obtaining samples . METHODS: The NP of 99 healthy adults was sampled with (1) nasal swab, (2) oral swab, and (3) nasal aspiration; 49 adults with common cold were sampled with an oral swab and nasal aspiration . Three selective agars were used to detect Streptococcus pneumoniae, Hemophilus influenzae, and Moraxella catarrhalis . RESULTS: Seventy-three percent of healthy adults and 74% of cold sufferers had at least one pathogen detected in the NP . Detection rates were 65% (oral NP swab), 38% (catheter aspiration), and 28% (nasal swab; p < 0.001) . Carriage rates for S . pneumoniae, M . catarrhalis, and H . influenzae were 45, 33, and 30%, respectively . Both a nasal and an oral sample were required for optimal detection . CONCLUSION: Bacterial pathogens were present in the NP of three-quarters of adults during wellness and during colds.

Microb Drug Resist, 2003 Fall, 9(3), 243 - 7
The novel conjugative transposon tn1207.3 carries the macrolide efflux gene mef(A) in Streptococcus pyogenes; Santagati M et al.; The macrolide efflux gene mef(A) of the Streptococcus pyogenes clinical strain 2812A was found to be carried by a 52-kb chromosomal genetic element that could be transferred by conjugation to the chromosome of other streptococcal species . The characteristics of this genetic element are typical of conjugative transposons and was named Tn1207.3 . The size of Tn1207.3 was established by pulsed-field gel electrophoresis (PFGE), and DNA sequencing analysis showed that the 7,244 bp at the left end of Tn1207.3 were identical to those of the pneumococcal Tn1207.1 element . Tn1207.3-like genetic elements were found to be inserted at a single specific chromosomal site in 12 different clinical isolates S . pyogenes exhibiting the M phenotype of resistance to macrolides and carrying the mef(A) gene . Tn1207.3 was transferred from S . pyogenes 2812A to Streptococcus pneumoniae, and sequence analysis carried out on six independent transconjugants showed that insertion of Tn1207.3 in the pneumococcal genome always occurred at a single specific site as in Tn1207.1 . Using MF2, a representative S . pneumoniae transconjugant, as a donor, Tn1207.3 was transferred again by conjugation to S . pyogenes and Streptococcus gordonii . The previously described nonconjugative element Tn1207.1 of S . pneumoniae appears to be a defective element, part of a longer conjugative transposon that carries mef(A) and is found in clinical isolates of S . pyogenes.

Minn Med, 2003 Aug, 86(8), 40 - 5
Prevention of perinatal group B streptococcal disease in Minnesota: results from a retrospective cohort study and new prevention guidelines; Ogunmodede F et al.; Group B Streptococcus (GBS) is an important cause of perinatal morbidity and mortality in the United States . In 1996, guidelines from the Centers for Disease Control and Prevention (CDC) recommended that prenatal care providers either screen all pregnant women for GBS carriage and offer intrapartum antibiotic prophylaxis (IAP) to women who test positive, or offer IAP to women who have risk factors for early-onset GBS (EOGBS) disease during pregnancy . A recent multi-state retrospective cohort compared the efficacy of the 2 methods and found the screening-based method to be significantly more effective at reducing the incidence of EOGBS . One of the study sites was the 7-county Minneapolis-St . Paul metropolitan area . Analysis of Minnesota data also found screening to be more effective in reducing EOGBS than the risk-based approach . In August 2002, the CDC published new guidelines that recommend adoption of a universal screening approach to management of perinatal GBS infections.

J Clin Microbiol, 2003 Sep, 41(9), 4445 - 7
Latex assay for serotyping of group B Streptococcus isolates; Slotved HC et al.; We developed a group B streptococcus (GBS) latex serotyping kit that reduces the numbers of GBS nontypeable isolates by nearly 50% . A total of 232 isolates were tested, and 203 isolates were serotyped by the GBS latex test, while the capillary precipitation test serotyped 184 isolates.

J Clin Microbiol, 2003 Sep, 41(9), 4442 - 4
Emergence of invasive serotype VIII group B streptococcal infections in Denmark; Ekelund K et al.; Serotype VIII group B streptococcus has only rarely been described outside Japan . The Streptococcus Unit, Statens Serum Institut, performed national surveillance of invasive group B streptococcal (GBS) diseases in Denmark in 1999 to 2002 and identified seven clinical GBS isolates of serotype VIII in blood from seven patients admitted to different hospitals.

J Clin Microbiol, 2003 Sep, 41(9), 4435 - 7
Streptococcus pneumoniae endocarditis: persistence of DNA on heart valve material 7 years after infectious episode; Branger S et al.; We amplified by PCR and sequenced Streptococcus pneumoniae rpoB from DNA of the cardiac valve of a man who had presented with pneumococcal endocarditis 7 years earlier . Histopathologically, the valve did not show evidence of endocarditis . This case raises the question of persistence of DNA without any evidence of infection.

J Clin Microbiol, 2003 Sep, 41(9), 4415 - 7
Confirmation of nontypeable Streptococcus pneumoniae-like organisms isolated from outbreaks of epidemic conjunctivitis as Streptococcus pneumoniae; Carvalho MG et al.; Eleven isolates representing five distinct outbreaks of pneumococcal conjunctivitis were examined for phenotypic and genetic characteristics . None of the strains possessed capsules, and all strains were susceptible to optochin, bile soluble, and Gen-Probe AccuProbe test positive . All 11 isolates were confirmed as Streptococcus pneumoniae by DNA-DNA reassociation experiments.

J Clin Microbiol, 2003 Sep, 41(9), 4178 - 83
Antimicrobial susceptibility and serotype distribution of Streptococcus pneumoniae and molecular characterization of multidrug-resistant serotype 19F, 6B, and 23F Pneumococci in northern Thailand; Watanabe H et al.; Penicillin-resistant Streptococcus pneumoniae is widely spread worldwide . Our study was undertaken to examine the susceptibility and serotypes of S . pneumoniae in northern Thailand . Ninety-three S . pneumoniae strains were isolated from 93 patients at Chiang Mai University Hospital, Chiang Mai, Thailand, from September 1999 to June 2000 . The strains were isolated from sputum (n = 51), blood (n = 15), nasopharynges (n = 14), and other sources (e.g., pus, ears, ascites, and cerebrospinal fluid) (n = 13) . Of the 93 isolates, 29 (31.2%) were susceptible, 24 (25.8%) showed intermediate resistance (MIC, 0.12 to 1.0 micro g/ml), and 40 (43.0%) were fully resistant (MIC, >/=2.0 micro g/ml) to penicillin G . Seven (46.7%) from blood, 5 (35.7%) from nasopharynges, 15 (29.4%) from sputum, and 2 (15.4%) from other sources were susceptible isolates . Serotyping with the use of antiserum revealed differences in the predominant types that were susceptible (6A, 11A, and 19A), intermediately resistant (6B and 23F), and fully resistant (6B, 19F, and 23F) . Molecular typing by pulsed-field gel electrophoresis of multidrug-resistant pneumococci showed four patterns (A, B, C, and D) for 16 isolates of serotype 19F, with pattern B being predominant (12 isolates) . This finding was different from that with the Taiwan multidrug-resistant serotype 19F clone . Eleven isolates of serotype 6B all showed pattern E, and nine isolates of serotype 23F showed two patterns (F and G), with pattern F being predominant (seven isolates) . This finding was similar to that with the Spanish multidrug-resistant serotype 23F clone . Our results indicated that the resistance of pneumococci to antibiotics in northern Thailand is progressing rapidly and that effort should be intensified to prevent any spread of pandemic multidrug-resistant serotypes 19F, 6B, and 23F.

J Clin Microbiol, 2003 Sep, 41(9), 4107 - 12
Analysis of loci required for determination of serotype antigenicity in Streptococcus mutans and its clinical utilization; Shibata Y et al.; We recently identified the genes responsible for the serotype c-specific glucose side chain formation of rhamnose-glucose polysaccharide (RGP) in Streptococcus mutans . These genes were located downstream from the rgpA through rgpF locus that is involved in the synthesis of RGP . In the present study, the corresponding chromosomal regions were isolated from serotype e and f strains and characterized . The rgpA through rgpF homologs were well conserved among the three serotypes . By contrast, the regions downstream from the rgpF homolog differed considerably among the three serotypes . Replacement of these regions in the different serotype strains converted their serotypic phenotypes, suggesting that these regions participated in serotype-specific glucose side chain formation in each serotype strain . Based on the differences among the DNA sequences of these regions, a PCR method was developed to determine serotypes . S . mutans was isolated from 198 of 432 preschool children (3 to 4 years old) . The serotypes of all but one S . mutans isolate were identified by serotyping PCR . Serotype c predominated (84.8%), serotype e was the next most common (13.3%), and serotype f occured rarely (1.9%) in Japanese preschool children . Caries experience in the group with a mixed infection by multiple serotypes of S . mutans was significantly higher than that in the group with a monoinfection by a single serotype.

Eur J Pharm Biopharm, 2003 Sep, 56(2), 197 - 206
A topological-substructural molecular design (TOPS-MODE) approach to determining pharmacokinetics and pharmacological properties of 6-fluoroquinolone derivatives; Cabrera Perez MA et al.; The topological-substructural molecular design approach was used to estimate the human bioavailability (F) and the minimum inhibitory concentration (MIC90) against Streptococcus pneumoniae from a data set of 17 and 19 fluoroquinolone derivatives, respectively . Both pharmacokinetics and pharmacological properties were well described by the present approach . The total spectral moments and local spectral moments that include the different fluoroquinolone rings, polar and non-polar areas and their interactions were calculated and weighted with the standard dipole moments and the electronegative difference between the atoms that form a bond . In order to obtain a qualitative model that permits the classification of drugs with high and moderate bioavailability, a linear discriminant analysis was carried out . The percentage of correct classification was 100% for compounds of the training set . The leave-one-out cross validation procedure showed an 88.23% of correct classification . Also, a quantitative model, by the piecewise linear regression was developed . The theoretically predicted values for human bioavailability was assessed by a correlation with in vivo rat bioavailability and the regression equation was used to predict this biopharmaceutical property for two new pre-clinical 6-fluoroquinolone derivatives . On the other hand, a linear regression model that explained the 84% of variance was developed to predict the MIC90 values . Finally, the role of a pharmacokinetic and pharmacological relationship in the design of new fluoroquinolones was evaluated in the Sitafloxacin framework, where 13 substituents were analyzed; halogens and methoxy groups had the best contributions to both properties . The present approach proved to be a good method for studying the pharmacokinetics and the pharmacological properties of new 6-fluoroquinolone candidates in drug development studies.

Arch Microbiol, 2003 Oct, 180(4), 298 - 302 Epub 2003 Sep 02.
Cloning and partial characterization of the gene encoding the putative elongation factor Ts of Streptococcus suis serotype 2; Martinez G et al.; Streptococcus suis infection has a substantial impact on the swine industry . In addition, S . suis serotype 2 is recognized as a zoonotic agent . In this paper, we report the cloning and complete sequence of the gene coding for the putative elongation factor Ts ( tsf-like) of S . suis . The putative tsf gene seems to be transcribed from a promoter located within the cloned DNA fragment, as its expression is not dependent on insertional orientation within the plasmid . One copy of the tsf gene was detected in the chromosome of S . suis by Southern blot analysis . Interestingly, the elongation factor Ts expressed by all reference strains of all S . suis serotypes were antigenically similar, as determined by Western blot.

Hybrid Hybridomics, 2003 Jun, 22(3), 147 - 51
Production of monoclonal antibody inhibiting dipeptidylaminopeptidase IV activity of Porphyromonas gingivalis; Teshirogi K et al.; Porphyromonas gingivalis is a Gram-negative anaerobic bacterial species implicated as an important pathogen in the development of adult periodontitis . We previously cloned a gene encoding dipeptydilaminopeptidase IV (DAPIV) from P . gingivalis . In the present study, for immunological diagnosis and development of passive immunization, we produced a mouse monoclonal antibody (MAb) capable of inhibiting the DAPIV activity of P . gingivalis using highly purified recombinant DAPIV as an immunogen . The constructed MAb, designated as MAb-Pg-DAP-1, significantly inhibited DAPIV activity in P . gingivalis, as well as slightly inhibited that in other gram-negative bacteria such as Porphyromonas endodontalis and Prevotella loesheii, whereas no inhibition was seen in the gram-positive bacteria Streptococcus mutans and Actinomyces viscosus . Furthermore, the MAb did not inhibit DAPIV enzyme activity in human serum . This novel MAb may be useful for the development of immunological diagnosis capability and in passive immunization.

Scand J Infect Dis, 2003, 35(6-7), 414 - 5
Household transmission of invasive group A streptococcus with necrotizing fasciitis; Laustrup HK et al.; A case of household transmission of invasive group A streptococcus with necrotizing fasciitis is presented . Antibiotic prophylaxis for close contacts in high-risk groups could be considered.

J Clin Invest, 2003 Sep, 112(5), 736 - 44
Group B streptococcal beta-hemolysin/cytolysin activates neutrophil signaling pathways in brain endothelium and contributes to development of meningitis; Doran KS et al.; Meningitis occurs when blood-borne pathogens cross the blood-brain barrier (BBB) in a complex interplay between endothelial cells and microbial gene products . We sought to understand the initial response of the BBB to the human meningeal pathogen group B Streptococcus (GBS) and the organism's major virulence factors, the exopolysaccharide capsule and the beta-hemolysin/cytolysin toxin (beta-h/c) . Using oligonucleotide microarrays, we found that GBS infection of human brain microvascular endothelial cells (HBMEC) induced a highly specific and coordinate set of genes including IL-8, Groalpha, Grobeta, IL-6, GM-CSF, myeloid cell leukemia sequence-1 (Mcl-1), and ICAM-1, which act to orchestrate neutrophil recruitment, activation, and enhanced survival . Most strikingly, infection with a GBS strain lacking beta-h/c resulted in a marked reduction in expression of genes involved in the immune response, while the unencapsulated strain generally induced similar or greater expression levels for the same subset of genes . Cell-free bacterial supernatants containing beta-h/c activity induced IL-8 release, identifying this toxin as a principal provocative factor for BBB activation . These findings were further substantiated in vitro and in vivo . Neutrophil migration across polar HBMEC monolayers was stimulated by GBS and its beta-h/c through a process involving IL-8 and ICAM-1 . In a murine model of hematogenous meningitis, mice infected with beta-h/c mutants exhibited lower mortality and decreased brain bacterial counts compared with mice infected with the corresponding WT GBS strains.

Rev Esp Enferm Dig, 2003 Jul, 95(7), 506 - 8, 503-5
Septic arthritis due to Streptococcus bovis in a patient with cirrhosis of enolic etiology; Marin E et al.; We present a case of bacteremia and septic arthritis due to Streptococcus bovis biotype I after shock, in a patient with liver cirrhosis of enolic etiology . Diagnosis was made based on a clinical setting of fever and a painful shoulder . The presence of colonic neoplasia was ruled out in this patient and the bacteremia developed without endocarditis.

J Antimicrob Chemother, 2003 Oct, 52(4), 616 - 22 Epub 2003 Sep 01.
Emergence of resistant Streptococcus pneumoniae in an in vitro dynamic model that simulates moxifloxacin concentrations inside and outside the mutant selection window: related changes in susceptibility, resistance frequency and bacterial killing; Zinner SH et al.; OBJECTIVES: According to the mutant selection window (MSW) hypothesis, resistant mutants are selected or enriched at antibiotic concentrations above the MIC but below the mutant prevention concentration (MPC) . To test this hypothesis, Streptococcus pneumoniae ATCC 49619 (MIC 0.1 mg/L; MPC 0.5 mg/L) was exposed to moxifloxacin concentrations below the MIC, above the MPC and between the MIC and MPC, i.e . within the MSW . METHODS: Daily administration of moxifloxacin for 3 consecutive days was mimicked using a two-compartment dynamic model with peripheral units containing a starting inoculum of 10(8) cfu/mL S . pneumoniae . Changes in susceptibility were examined by repeated MIC determinations and by plating the specimens on agar containing zero, 2 x MIC, 4 x MIC and 8 x MIC of moxifloxacin . RESULTS: Both in terms of the MIC and resistance frequency, S . pneumoniae resistance developed at concentrations that fell inside the MSW {ratios of 24 h area under the curve (AUC24) to MIC between 24 and 47 h} . A Gaussian-like function fitted the AUC24/MIC-dependent increases in MIC and resistance frequency with central points at AUC24/MICs of 38 and 42 h, respectively, where resistant mutants are enriched selectively . Selective enrichment of resistant mutants was not seen at AUC24/MICs <10 h or >100 h . CONCLUSIONS: These data suggest that AUC24/MICs >100 h may protect against the selection of resistant S . pneumoniae mutants . Since the usual 400 mg dose of moxifloxacin provides much higher AUC24/MIC (270 h), it is expected to prevent mutant selection at clinically achievable concentrations . Also, these data provide further support for the MSW hypothesis.

Mol Microbiol, 2003 Sep, 49(6), 1639 - 55
Genes controlled by the essential YycG/YycF two-component system of Bacillus subtilis revealed through a novel hybrid regulator approach; Howell A et al.; The YycG/YycF two-component system, originally identified in Bacillus subtilis, is very highly conserved and appears to be specific to low G + C Gram-positive bacteria . This system is required for cell viability, although the basis for this and the nature of the YycF regulon remained elusive . Using a combined hybrid regulator/transcriptome approach involving the inducible expression of a PhoP'-'YycF chimerical protein in B . subtilis, we have shown that expression of yocH, which encodes a potential autolysin, is specifically activated by YycF . Gel mobility shift and DNase I footprinting assays were used to show direct binding in vitro of purified YycF to the regulatory regions of yocH as well as ftsAZ, previously reported to be controlled by YycF . Nucleotide sequence analysis and site-directed mutagenesis allowed us to define a potential consensus recognition sequence for the YycF response regulator, composed of two direct repeats: 5'-TGT A/T A A/T/C-N5-TGT A/T A A/T/C-3' . A DNA-motif analysis indicates that there are potentially up to 10 genes within the B . subtilis YycG/YycF regulon, mainly involved in cell wall metabolism and membrane protein synthesis . Among these, YycF was shown to bind directly to the region upstream from the ykvT gene, encoding a potential cell wall hydrolase, and the intergenic region of the tagAB/tagDEF divergon, encoding essential components of teichoic acid biosynthesis . Definition of a potential YycF recognition sequence allowed us to identify likely members of the YycF regulon in other low G + C Gram-positive bacteria, including several pathogens such as Listeria monocytogenes, Staphylococcus aureus and Streptococcus pneumoniae.

Mol Microbiol, 2003 Sep, 49(6), 1615 - 25
Attenuated virulence of Streptococcus agalactiae deficient in D-alanyl-lipoteichoic acid is due to an increased susceptibility to defensins and phagocytic cells; Poyart C et al.; D-alanylation of lipoteichoic acid (LTA), allows Gram-positive bacteria to modulate their surface charge, regulate ligand binding and control the electromechanical properties of the cell wall . In this study, the role of D-alanyl LTA in the virulence of the extracellular pathogen Streptococcus agalactiae was investigated . We demonstrate that a DltA- isogenic mutant displays an increased susceptibility to host defence peptides such as human defensins and animal-derived cationic peptides . Accordingly, the mutant strain is more susceptible to killing by mice bone marrow-derived macrophages and human neutrophils than the wild-type strain . In addition, the virulence of the DltA- mutant is severely impaired in mouse and neonatal rat models . This mutant was eliminated more rapidly than the wild-type strain from the lung of three-week-old mice inoculated intranasally and, consequently, is unable to induce a pneumonia . Finally, after intravenous injection of three-week-old mice, the survival of the DltA- mutant is markedly reduced in the blood in comparison to that of the wild-type strain . We hypothesize that the decreased virulence of the DltA- mutant is a consequence of its increased susceptibility to cationic antimicrobial peptides and to killing by phagocytes . These results demonstrate that the D-alanylation of LTA contributes to the virulence of S . agalactiae.

Biochemistry, 2003 Sep 9, 42(35), 10372 - 84
Structure and dynamics of the lantibiotic mutacin 1140; Smith L et al.; Mutacin 1140 is a member of a family of ribosomally synthesized peptide bacteriocins called lantibiotics (lanthionine-containing antibiotics) and is produced by the Gram-positive bacterium Streptococcus mutans . Mutacin 1140 has been shown to be effective against a broad array of Gram-positive bacteria . Chromatography and mass spectroscopy data suggested that mutacin 1140 forms a small compact structure . Nuclear magnetic resonance (NMR) data and restrained molecular dynamics simulations showed that mutacin 1140 interconverts between multiple structures . Calculations of scalar (J) coupling constants showed the best agreement with experimental values when the entire population-weighted ensemble of structures was used, providing independent support for the ensemble . Representative structures from each major group in the ensemble had a common feature in which they are all kinked around the hinge region forming a horseshoe-like shape, and the regions of flexibility of the molecule were limited and well-defined . The structures determined in this study provide a starting point for modeling the mutacin 1140-membrane interactions and pore formation.

J Leukoc Biol, 2003 Sep, 74(3), 448 - 55
Many chemokines including CCL20/MIP-3alpha display antimicrobial activity; Yang D et al.; Previous studies have demonstrated that beta-defensins exhibit chemotactic activity by sharing the chemokine receptor CCR6 with the CC chemokine ligand CCL20/macrophage-inflammatory protein-3alpha (MIP-3alpha) . Structural analysis of CCL20/MIP-3alpha revealed that most of the positively charged residues are concentrated at one area of its topological surface, a characteristic considered to be important for the antimicrobial activity of defensins . Here, we report that similar to defensins, CCL20/MIP-3alpha has antimicrobial effects on Escherichia coli, Pseudomonas aeruginosa, Moraxella catarrhalis, Streptococcus pyogenes, Enterococcus faecium, Staphylococcus aureus, and Candida albicans . Additionally, by screening a total of 30 human chemokines, we have identified an additional 17 human chemokines, which exhibit antimicrobial activity in vitro . Collectively, about two-thirds of the chemokines investigated so far has the capacity to kill microorganisms in vitro, suggesting that antimicrobial activity may be another host-defense function for certain chemokines . Comparison of the structural characteristics between antimicrobial and nonantimicrobial chemokines suggests that topological formation of a large, positively charged electrostatic patch on the surface of the molecule is likely to be a common structural feature of antimicrobial chemokines.

J Biol Chem, 2003 Nov 7, 278(45), 44361 - 8 Epub 2003 Aug 29.
The essential C family DnaE polymerase is error-prone and efficient at lesion bypass; Bruck I et al.; DnaE-type DNA polymerases belong to the C family of DNA polymerases and are responsible for chromosomal replication in prokaryotes . Like most closely related Gram-positive cells, Streptococcus pyogenes has two DnaE homologs Pol C and DnaE; both are essential to cell viability . Pol C is an established replicative polymerase, and DnaE has been proposed to serve a replicative role . In this report, we characterize S . pyogenes DnaE polymerase and find that it is highly error-prone . DnaE can bypass coding and noncoding lesions with high efficiency . Error-prone extension is accomplished by either of two pathways, template-primer misalignment or direct primer extension . The bypass of abasic sites is accomplished mainly through "dNTP-stabilized" misalignment of template, thereby generating (-1) deletions in the newly synthesized strand . This mechanism may be similar to the dNTP-stabilized misalignment mechanism used by the Y family of DNA polymerases and is the first example of lesion bypass and error-prone synthesis catalyzed by a C family polymerase . Thus, DnaE may function in an error-prone capacity that may be essential in Gram-positive cells but not Gram-negative cells, suggesting a fundamental difference in DNA metabolism between these two classes of bacteria.

Int Immunopharmacol, 2003 Oct, 3(10-11), 1447 - 56
Thalidomide modulation of the immune response in female B6C3F1 mice: a host resistance study; Karrow NA et al.; Previously, we have reported that thalidomide (Thd) treatment can modulate the immune responses in female B6C3F1 mice . The present study was designed to evaluate whether or not these immunomodulatory responses were of sufficient magnitude to alter host resistances in a number of pathogen and tumor models . B6C3F1 mice were treated intraperitoneally with Thd (30-150 mg/kg) for 14 or 28 days, then inoculated with either Plasmodium yeolii, PYB6 fibrosarcoma tumor cells, B16F10 melanoma tumor cells, Listeria monocytogenes, or Streptococcus pneumoniae . Significant dose-dependent protection against B16F10 and L . monocytogenes was observed in mice that were treated with Thd . Furthermore, time course study using bacterial colony-forming units per spleen and liver as the endpoints indicated that the protective effect of Thd on host resistance to L . monocytogenes was time-dependent . In contrast, Thd treatment did not affect host resistance to P . yeolii, S . pneumoniae and PYB6 tumor . Additionally, the effect of Thd on the phagocytic function of the mononuclear phagocyte system (MPS) was evaluated following intravenous injection of 51Cr-labeled sRBCs . The overall phagocytic activity of MPS was not significantly altered by Thd treatment . In conclusion, these results demonstrate that Thd immunomodulation altered host resistance to B16F10 and L . monocytogenes; and selective modulation of Thd on the immune system may be responsible for the pathogen or tumor-specific effect of this compound.

Proteins, 2003 Oct 1, 53(1), 88 - 100
Understanding the acylation mechanisms of active-site serine penicillin-recognizing proteins: a molecular dynamics simulation study; Oliva M et al.; Beta-lactam antibiotics inhibit enzymes involved in the last step of peptidoglycan synthesis . These enzymes, also identified as penicillin-binding proteins (PBPs), form a long-lived acyl-enzyme complex with beta-lactams . Antibiotic resistance is mainly due to the production of beta-lactamases, which are enzymes that hydrolyze the antibiotics and so prevent them reaching and inactivating their targets, and to mutations of the PBPs that decrease their affinity for the antibiotics . In this study, we present a theoretical study of several penicillin-recognizing proteins complexed with various beta-lactam antibiotics . Hybrid quantum mechanical/molecular mechanical potentials in conjunction with molecular dynamics simulations have been performed to understand the role of several residues, and pK(a) calculations have also been done to determine their protonation state . We analyze the differences between the beta-lactamase TEM-1, the membrane-bound PBP2x of Streptococcus pneumoniae, and the soluble DD-transpeptidase of Streptomyces K15 .

Diagn Microbiol Infect Dis, 2003 Aug, 46(4), 291 - 4
Antimicrobial susceptibility profile among beta-haemolytic Streptococcus spp . collected in the SENTRY Antimicrobial Surveillance Program--North America, 2001; Biedenbach DJ et al.; The surveillance of antimicrobial resistance among beta-hemolytic Streptococcus spp . is an important health care concern due to the serious nature of the diseases that are caused by these pathogens and the emerging antimicrobial resistances . National and international studies have documented diverse rates of resistance to macrolide and lincosamide agents . The SENTRY Antimicrobial Surveillance Program evaluated the resistance rates of beta-hemolytic Streptococcus spp . to several drug classes including erythromycin and clindamycin during the 2001 study year . Twenty-five medical centers in North America contributed 787 isolates from serogroups A (SGA; 397 strains), B (SGB; 318 strains), G (SGG; 45 strains), C (SGC; 19 strains), and F (SGF; eight strains) . Isolates were tested at a reference center by broth microdilution using NCCLS methods . A subset of isolates were characterized by molecular methods to determine the presence of erm and mef resistance mechanisms . All isolates were susceptible to beta-lactams, linezolid, vancomycin, chloramphenicol, quinupristin/dalfopristin, and fluoroquinolones . Garenoxacin (MIC(90,) 0.06 microg/ml) was the most potent fluoroquinolone tested . Tetracycline was inactive against SGB (14.8% susceptible) compared to SGC, SGG, SGF and SGA (48.9-85.6% susceptible) . Resistance to erythromycin and clindamycin was highest among SGB isolates with M-phenotypes (mef) representing the majority (59.1%) of strains . Among isolates randomly selected for genotypic characterization, eight strains had mef (A), 16 had erm (A) {subclass erm (TR)}, seven had erm (B) and one strain had erm (A) {subclass erm (TR)} and mef (A) present . These data when compared to previous SENTRY Program analysis showed macrolide resistance has remained stable over the last five years and M-phenotypes are the most prevalent expression of MLS(B) resistance in North America.

Expert Opin Biol Ther, 2003 Sep, 3(6), 975 - 84
Glycoconjugate vaccines to prevent group B streptococcal infections; Paoletti LC et al.; Group B Streptococcus (GBS) is an opportunistic pathogen of humans . At-risk populations include neonates born to colonised mothers, peripartum women, diabetics, and the elderly with underlying illnesses . Vaccines to prevent GBS disease have been developed by coupling purified capsular polysaccharide (CPS) antigen of GBS with an immunogenic protein carrier . Glycoconjugate vaccines against all nine currently identified GBS serotypes have been synthesised and shown to be immunogenic in mice, rabbits and baboons in preclinical trials . Healthy adults have safely received conjugate vaccines prepared with GBS types Ia, Ib, II, III, and V CPSs in Phase I and II clinical trials . These vaccines elicited CPS-specific antibody that opsonised GBS for in vitro killing by human peripheral blood leukocytes in the presence of complement . Results from these preclinical and clinical studies strongly suggest that GBS conjugate vaccines will be effective in preventing diseases caused by GBS.

Recenti Prog Med, 2003 Sep, 94(9), 395 - 8
{Acute post-infective glomerulonephritis}; Moroni G et al.; In children post-infectious acute glomerulonephritis is usually caused by beta-hemolytic streptococcus and has a fair prognosis with spontaneous remission in most cases . Rarely, however, the disease may be complicated by oliguria and/or severe hypertension which can cause cardiac congestion or cerebral edema . In adults the acute glomerulonephritis may be caused by a number of different micro-organisms and it often develops in patients with other diseases . The prognosis may be severe and is worsening over the years . The risk of chronic renal failure is increased in patients with crescents and with large interstitial infiltrates . A renal biopsy is recommended in adults with acute glomerulonephritis to make possible a differential diagnosis with other diseases presenting with a nephritic syndrome, to assess the prognosis and to evaluate the pro's and the con's of a treatment with steroid and/or immunosuppressive agents.

Eur J Clin Microbiol Infect Dis, 2003 Sep, 22(9), 561 - 5 Epub 2003 Aug 27.
Comparative in vitro activity of faropenem and 11 other antimicrobial agents against 250 invasive Streptococcus pneumoniae isolates from France; Decousser JW et al.; The aim of the study presented here was to evaluate the in vitro activity of faropenem, a new member of the penem class intended for oral administration, compared with 11 other antimicrobial agents against a large number of Streptococcus pneumoniae strains isolated from adults and children with bloodstream infections in France . The minimum inhibitory concentration of faropenem against 90% of the pediatric strains tested was generally one to two dilutions lower than the most potent beta-lactam agents (i.e., 0.5 micro g/ml for faropenem vs . 1 for amoxicillin, 1 for cefotaxime and 0.5 micro g/ml for ceftriaxone) . Against the adult strains, only moxifloxacin had a MIC(90) value similar to faropenem (i.e., 0.25 micro g/ml for both agents) . Faropenem seems to be a promising antimicrobial agent for the treatment of adult and pediatric Streptococcus pneumoniae infections.

Immunol Lett, 2003 Sep 8, 88(3), 227 - 39
Characterisation of mouse monoclonal antibodies for pneumolysin: fine epitope mapping and V gene usage; Suarez-Alvarez B et al.; Pneumolysin (PLY) is a cholesterol-dependent cytolysin (CDC) produced by Streptococcus pneumoniae, the main cause of community-acquired pneumonia . We have applied a set of diverse molecular methodologies (PCR-derived PLY peptides, biopanning of a library of phage-displayed random nonapeptides, indirect ELISA and competition tests with soluble peptides) to achieve concordant complementary observations in order to obtain a fine epitope mapping of three mouse monoclonal antibodies (PLY-4, PLY-7 and PLY-8) for PLY . PLY-4 seems to recognise a conformation-dependent epitope with a core reactivity involving R232 . The epitopes recognised by PLY-7 and PLY-8 are within the sequences (401)GQDLTAH(407) and (450)KRTISIWGT(458), respectively . PLY-7 also recognises suilysin (SLY), in which the homologous reactive amino acid stretch is (429)GVNLTSH(435) . In a homology model of PLY with the crystal structure of perfringolysin O (PFO), R232 is part of a well-exposed contorted loop on the edge of the concave and convex faces of domain 1 . The sequences reactive with PLY-7 and PLY-8 would conform one of the loops at the bottom of domain 4 and a beta strand of one of the two beta sheets of this domain, respectively . Western blot analyses carried out with anti-PLY rabbit IgG and polyclonal mouse serum identified stretches comprising residues 40-98, 199-248, 352-414 and 415-471 of PLY as immunogenic and antigenic; altogether with their recognition by the monoclonal antibodies herein considered, these results stress the immunological significance of domains 1 and 4 of the PLY molecule . PLY-4, PLY-7 and PLY-8 share the same Vkappa chain; this chain and that of the PLY-5 monoclonal antibody are essentially in germline configuration, whereas the VH regions of these monoclonals come from diverse gene segments and are mutated.

J Periodontal Res, 2003 Oct, 38(5), 477 - 81
The subgingival microflora in phenytoin-induced gingival hyperplasia; Takada K et al.; OBJECTIVES: Microbial flora and gingival conditions were compared between a group of patients with phenytoin-induced gingival hyperplasia as a test group, a control group of patients who were administered phenytoin without gingival hyperplasia and a blank group who took no phenytoin and no gingival hyperplasia in mentally retarded patients . MATERIALS AND METHODS: Subgingival plaque samples were collected from a PHT-induced overgrown gingival pocket and microbiological experiments were performed by culture and PCR methods . RESULTS: The predominant genera in total cultivable bacteria from subgingival plaque samples were streptococcus and actinomyces with recovery ranges of 37.6-42.1% and 23.4-25.5% of total bacteria, respectively, in all groups . The test group showed a significantly higher level of obligate Gram-negative rods than the control and blank groups . Black-pigmented obligate anaerobic Gram-negative rods were detected in 10.3% of total cultivable bacteria in the test group . The black-pigmented rods were predominantly Prevotella intermedia in the test group and Prevotella nigrescens in the control and blank groups . Porphyromonas gingivalis and Porphyromonas endodontalis were also detected in the test group with small values . CONCLUSIONS: These results suggested that black-pigmented rods, particularly P . intermedia, could be habitable in the environment of gingival hyperplasia.

J Vet Med Sci, 2003 Jul, 65(7), 787 - 92
Pneumonia in horses induced by intrapulmonary inoculation of Streptococcus equi subsp . zooepidemicus; Yoshikawa H et al.; To evaluate the possibility that Streptococcus equi subsp . zooepidemicus (S.z) the causative bacterial agent of equine shipping fever pneumonia (ESFP), as well as to investigate its pathogenesis, 10 horses (seven Thoroughbreds and three Anglo-Arab species, ranging from 2-4 years in age) were experimentally inoculated, via an endoscope, into bronchus of the lung lobe with a dose of 30 ml of 1-7 x 10(8) CFU/ml of S.z . After inoculation, autopsy and pathological examinations were sequentially conducted 30 min, 1, 2, 3, 4, 17, 20 hr and 2 weeks later . Pneumonia induced by the intrapulmonary inoculation of S.z was characterized by small purulent pneumonic foci in the inoculated areas . With the lapse of time, these foci developed into serous hemorrhagic pneumonia, hemorrhagic purulent pneumonia, and then purulent, coagulation necrotic pneumonia . These pathomorphological characteristics of experimental pneumonia closely resemble those naturally occurring ESFP . There is strong evidence that S.z . is implicated as a causal factor in ESFP . S.z . grew in the mucus, exudate, and pulmonary effusions . Further, the bacteria showed resistance against phagocytosis by pulmonary alveolar macrophages (PAM) and neutrophils . Inhibition of PAM and neutrophil function is considered to be important in the development of pneumonia . With the progression of the disease, the neutrophils often adhered to the endothelial surface of the alveolar capillary lumen and played a role in generating coagulation necrosis of lung tissues.

J Dent Res, 2003 Sep, 82(9), 753 - 7
Degradation of antimicrobial histatin-variant peptides in Staphylococcus aureus and Streptococcus mutans; Groenink J et al.; Histidine-free variants of salivary histatin 5 have a broad antimicrobial activity against various bacteria . In relation to a possible therapeutic application, we were interested in the susceptibility of these small peptides (14 amino acids long) to microbial proteinases and whether this affects their antimicrobial activity . Analyses by SDS-PAGE of supernatants of peptide-bacteria incubation showed a reduction in protein bands within 15 minutes' incubation, as a result of cellular internalization . Degradation products of dhvar1 and dhvar2 appeared within one hour in the supernatants of Streptococcus mutans and Staphylococcus aureus . In contrast, the variants dhvar3 and dhvar4 were more resistant to degradation under the same conditions . MALDI-TOF analyses identified cleavage of dhvar1 and dhvar2 at Glu(6) . The N-terminal peptide part (1-6) of dhvar1 and 2 showed no bactericidal activity, while peptide fragment (7-14) showed a highly reduced bactericidal activity.

Eur J Immunol, 2003 Sep, 33(9), 2353 - 60
Localization of peptide/MHC class II complexes in macrophages following antigen processing of viable Streptococcus pyogenes; von Delwig A et al.; The subcellular localization of peptide/MHC complexes was investigated during processing of the surface M5 protein from Streptococcus pyogenes . Bone marrow-derived macrophages were pulsed with viable S . pyogenes for 20 min followed by various periods of chase . T hybridoma cells detected complexes of one epitope, M5(17-31) with E(d) on the surface of macrophages within 30 min of chase . In contrast, complexes with another epitope, M5(308-319) with A(d) peaked later . Intracellular localization of peptide/MHC-II complexes was studied by subcellular fractionation and detection of complexes in fractions by T hybridoma cells . M5(17-31)/E(d) complexes were detected in light membrane fractions containing plasma membrane and early endosomes by 10-30 min . M5(308-319)/A(d) complexes were detected in these light membranes after 3 h of chase . Thus, the time course of M5(308-319)/A(d) presentation was delayed relative to M5(17-31)/E(d) . However, neither type of complex was detected at any time in fractions containing phagosomes . Both species of peptide/MHC complexes localized to endocytic compartments, indicating a role for endosomes in presentation of antigens from phagocytosed bacteria.

Rev Neurol, 2003 Aug 1-15, 37(3), 201 - 6
{Cerebral abscesses of oral origin}; Limeres-Posse J et al.; INTRODUCTION: It has been suggested that between 3% and 13% of the cerebral abscesses (CA) are presumably associated to oral infections or dental procedures . AIM: Determine the prevalence of CA of oral origin, discussing their clinical and microbiological characteristics . PATIENTS AND METHODS: Retrospectively, 54 cases of CA diagnosed in 3 hospitals of Galicia between 2001 and 2002 were reviewed . RESULTS: A presumed oral portal of entry was recorded in 6 patients (11.1%); 4 cases were associated to oral infections and the remaining 2 had received dental treatment in the months prior to the onset of symptoms . Half of the patients showed irrelevant medical record, 2 had had previous extracranial abscesses and 1 presented a type A immunoglobulin deficiency . In 4 cases, the microbiological analysis was positive and typical oral bacteria (Streptococcus viridans and Peptostreptococcus spp.) were identified . CONCLUSIONS: The results of this study suggest that a significant number of CA are probably of oral origin . In consequence, to maintain a good oral health status is important and specific prophylactic measures before any dental procedure should be applied, especially in patients with risk recognized factors.

Clin Oral Investig, 2003 Dec, 7(4), 212 - 6 Epub 2003 Aug 22.
Effects of low-concentrated chlorhexidine on growth of Streptococcus sobrinus and primary human gingival fibroblasts; Dogan S et al.; The aim of this study was to investigate the in vitro effects of low concentrations of chlorhexidine (CHX) on the proliferation of Streptococcus sobrinus (ATCC 33478) and primary human gingival fibroblasts (HGF) . Liquid cultures of bacteria or human gingival fibroblasts were exposed to CHX concentrations ranging from 0.07 to 40 microM in microtiter plates at 37 degrees C for 24 h . Bacteria or cells grown without CHX served as controls . The effects of CHX were determined either by measurements of the optical density (OD) of bacterial cultures or by evaluation of cell growth with the DNA-intercalating fluorescent stain H33342 in comparison to untreated controls . Results were evaluated calculating means and standard deviations . Data were statistically analyzed by an ANOVA using Post Hoc tests ( p<0.005) . No growth inhibition of S . sobrinus was found at concentrations between 0.07 and 0.15 microM CHX, whereas 0.3 microM CHX led to an elongated (2 h more) lag phase and 0.6 microM CHX induced a lag phase of 4 h more and a minor inclination of the curve in the log phase . Concentrations of CHX>/=1.25 microM completely inhibited growth of S . sobrinus . On the contrary, CHX showed no significant effect on growth of HGF at concentrations </=5 microM . A slight growth inhibition was only observed at a concentration of 5 microM . CHX-concentrations of 10 and 20 microM reduced cell growth to 88 or 75% of control assays . Data analysis showed that overall treatment effects were highly significant ( p<0.005) . Our data reveal that chlorhexidine inhibits proliferation of S . sobrinus even at very low concentrations while concentrations of CHX</=5 microM are not cytotoxic to human gingival fibroblasts.

Eur Arch Otorhinolaryngol, 2003 Aug, 260(7), 401 - 3 Epub 2003 Feb 13.
Ludwig's angina: a clinical review; Srirompotong S et al.; Ludwig's angina is caused by a rapidly expanding cellulitis of the floor of the mouth and is characterized by a brawny induration of the floor and suprahyoid region (bilaterally), with an elevation of the tongue potentially obstructing the airway . In the pre-antibiotic era, Ludwig's angina was frequently fatal; however, antibiotics and aggressive surgical intervention have significantly reduced mortality . We reviewed nine patients with Ludwig's angina between July 1996 and June 2002, all of whom presented with fever, neck swelling, bilateral submandibular swelling and elevation of the tongue . In eight patients (89%) a dental infection appeared to be the underlying cause . High-dosage intravenous antibiotics directed towards the suspected causative microorganisms were given to all of the patients: two were treated successfully with conservative medical management, while seven underwent surgical drainage (a tracheotomy was necessary in one patient) . Routine aerobic cultures were done on samples of drained material and the predominant microorganisms were Streptococcus species in two patients; there were none in the other five . Two patients had post-operative complications, but all recovered.

Antimicrob Agents Chemother, 2003 Sep, 47(9), 2974 - 7
Activity of daptomycin against recent North American isolates of Streptococcus pneumoniae; Restrepo MI et al.; Daptomycin MICs at which 50% of isolates were inhibited (MIC(50)s) and MIC(90)s determined by the NCCLS broth microdilution method were both 0.25 microg/ml (range, 0.06 to 2 microg/ml) for 350 pneumococcal isolates . MICs determined by E test strips on commercially prepared Mueller-Hinton sheep blood agars with different calcium contents were 2 to 3 dilutions higher than those determined by strips that contained daptomycin plus calcium . Daptomycin zone diameters varied little on the same media.

Antimicrob Agents Chemother, 2003 Sep, 47(9), 2844 - 9
Presence of the tet(O) gene in erythromycin- and tetracycline-resistant strains of Streptococcus pyogenes and linkage with either the mef(A) or the erm(A) gene; Giovanetti E et al.; Sixty-three recent Italian clinical isolates of Streptococcus pyogenes resistant to both erythromycin (MICs >or=1 microg/ml) and tetracycline (MICs >or= 8 microg/ml) were genotyped for macrolide and tetracycline resistance genes . We found 19 isolates carrying the mef(A) and the tet(O) genes; 25 isolates carrying the erm(A) and tet(O) genes; and 2 isolates carrying the erm(A), tet(M), and tet(O) genes . The resistance of all erm(A)-containing isolates was inducible, but the isolates could be divided into two groups on the basis of erythromycin MICs of either >128 or 1 to 4 microg/ml . The remaining 17 isolates included 15 isolates carrying the erm(B) gene and 2 isolates carrying both the erm(B) and the mef(A) genes, with all 17 carrying the tet(M) gene . Of these, 12 carried Tn916-Tn1545-like conjugative transposons . Conjugal transfer experiments demonstrated that the tet(O) gene moved with and without the erm(A) gene and with the mef(A) gene . These studies, together with the results of pulsed-field gel electrophoresis experiments and hybridization assays with DNA probes specific for the tet(O), erm(A), and mef(A) genes, suggested a linkage of tet(O) with either erm(A) or mef(A) in erythromycin- and tetracycline-resistant S . pyogenes isolates . By amplification and sequencing experiments, we detected the tet(O) gene ca . 5.5 kb upstream from the mef(A) gene . This is the first report demonstrating the presence of the tet(O) gene in S . pyogenes and showing that it may be linked with another gene and can be moved by conjugation from one chromosome to another.

Antimicrob Agents Chemother, 2003 Sep, 47(9), 2765 - 9
Impact of azithromycin administration for trachoma control on the carriage of antibiotic-resistant Streptococcus pneumoniae; Batt SL et al.; Community distribution of azithromycin has an important role to play in trachoma control . Previous studies have suggested that this may increase the prevalence of macrolide-resistant Streptococcus pneumoniae . S . pneumoniae was isolated from children under 7 years of age in Rombo District, northern Tanzania, before and 2 and 6 months after community-wide administration of azithromycin . Overall carriage rates were 11, 12, and 7%, respectively . Only one macrolide-resistant isolate carrying the mef gene was obtained 6 months after azithromycin administration . This contrasted with cotrimoxazole and penicillin resistance, both of which were common (cotrimoxazole resistance, 42, 43, and 47%, and penicillin resistance, 21, 17, and 16% at baseline, 2 months, and 6 months, respectively) . There was a significant association between cotrimoxazole and penicillin resistance (P < 0.0001, Fisher's exact) . These data suggest that in communities where macrolide resistance is rare, azithromycin distribution for trachoma control is unlikely to increase the prevalence of resistant organisms.

Leg Med (Tokyo), 2001 Sep, 3(3), 127 - 33
Application of in situ PCR to diagnose pneumonia in medico-legal autopsy cases; Nakamura M et al.; In situ polymerase chain reaction (in situ PCR) can detect specific sequences of DNA, such as those of micro-organisms in human tissue samples . In forensic medicine, there are many cases implicated with infection, and pneumonia is an especially common finding in autopsy cases . In the present study, we tried to detect the presence of bacterial infections in lung tissue samples . The experiment was performed with ten paraffin-embedded lung tissue samples, including three non-pneumonia cases using specific primers for Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus equisimilis, and a DIG Oligonucleotide 3'-End Labeling Kit (Boehringer Mannheim) . The findings showed that at least one or all three species of bacterial flora in the alveoli could be detected in all seven pneumonia cases, and that some leukocyte cytoplasms, after antigen-antibody and color emission chemical reactions, were also observed to have changed color due to phagocytosis . Detection of bacterial DNA in the leukocyte cytoplasm is a sign of vital reaction and differentiates between antemortem and postmortem infection . The present findings revealed that in situ PCR had the advantage that it helped identifying specific bacteria in the lung tissues with pneumonia.

J Med Food, 2003 Summer, 6(2), 99 - 105
Antioxidant and antimicrobial activity of Cissus quadrangularis L; Chidambara Murthy KN et al.; Extracts of Cissus quadrangularis L . were tested for antioxidant activity by beta-carotene linoleic acid model and also by 1,1-diphenyl-2-picrylhydrazyl model . The ethyl acetate fraction of both fresh and dry stem extracts at a concentration of 100 ppm showed 64.8% antioxidant activity in the beta-carotene linoleic acid system and 61.6% in the 1,1-diphenyl-2-picrylhydrazyl system . This fraction showed the presence of sterols, vitamin C, and tannins as phytoconstituents . The antioxidant activity of methanol extract and aqueous extract were comparatively less significant than that of ethyl acetate extract, and n-hexane extract showed the least activity . The ethyl acetate extract and methanol extract of both fresh and dry stems further exhibited antimicrobial activity against Gram-positive bacteria, including Bacillus subtilis, Bacillus cereus, Staphylococcus aureus, and Streptococcus species . The results of the study have implications in the use of C . quadrangularis as an antibacterial agent and more so as an antioxidant in several applications requiring these properties.

J Infect Dis, 2003 Sep 1, 188(5), 666 - 70 Epub 2003 Aug 20.
Pulmonary immunoglobulin responses to Streptococcus pneumoniae are altered but not reduced in human immunodeficiency virus-infected Malawian adults; Gordon SB et al.; We tested the hypothesis that human immunodeficiency virus (HIV)-infected adults have a specific defect in anti-pneumococcal capsular polysaccharide (Pn-specific) immunoglobulin (Ig) in fluid obtained from the lower respiratory tract . Higher levels of total IgG and IgM were present in bronchoalveolar lavage samples from HIV-infected subjects than in those from HIV-uninfected subjects . Pn-specific IgG and IgM in bronchoalveolar lavage samples were not significantly different between HIV-infected and -uninfected subjects . After pneumococcal infection, HIV-infected patients had higher bronchoalveolar lavage levels of Pn-specific IgG than HIV-infected patients without recent infection (geometric means, 387 vs . 30 ng/mL, P=.001).

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