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Orv Hetil, 2003 Jan 12, 144(2), 59 - 65
{Toxic shock syndrome caused by pyogenic bacteria}; Gabor Z et al.; Case reports and review of the literature . INTRODUCTION: Severe toxic shock syndrome caused by invasive infection with pyogenic bacteria Staphylococcus aureus or group A Streptococcus pyogenes, with high mortality rates in cases of the latter, remained one of the most problematic chapters of critical care medicine to date . AIMS: To give an overview on the epidemiology, clinical manifestations, the complex therapeutical approaches of the syndrome and, on the role and mechanisms of action of bacterial superantigens in the pathophysiological processes as well . METHODS AND RESULTS: Literary data, and some illustrative selected cases demonstrate that, the incidence of TSS shows increasing tendency worldwide and, that otherwise healthy, younger people are the most frequently affected . As for prognosis: early diagnosis and treatment with sufficient radicality are of decisive importance.

Euro Surveill, 1998 Feb, 3(2), 11 - 14
Surveillance of systemic invasive disease caused by group A Streptococcus in Italy 1994-1996; Suligoi B et al.; In late May 1994, following reports of an outbreak of group A beta-haemolytic streptococcus (GAS) in the United Kingdom, the Istituto Superiore di Sanita (ISS) set up a surveillance system for systemic invasive GAS disease . The surveillance system was als

Mayo Clin Proc, 2003 Mar, 78(3), 289 - 93
Validation and modification of streptococcal pharyngitis clinical prediction rules; McGinn TG et al.; OBJECTIVE: To validate a simplified version of the Walsh clinical prediction rules (CPRs) for the presence of streptococcal pharyngitis in an inner-city, ethnically diverse population . PATIENTS AND METHODS: This prospective study conducted in New York City, NY, from January 1,1997, to May 31,1997, consisted of 171 consecutive adult walk-in patients who presented with symptoms of upper respiratory tract infection and/or sore throat . The patients were assessed by using 5 clinical factors: cough, exposure to known streptococcal contact, temperature, tonsillar-pharyngeal exudates, and cervical lymphadenopathy . Throat cultures for group A beta-hemolytic streptococcus were obtained from all patients . Clinicians assessing the patients were unaware of throat culture results, and those processing the throat cultures were blinded to the clinical predictors . RESULTS: The prevalence of streptococcal pharyngitis was 24% (95% confidence interval, 18%-30%) . The simplified version of the Walsh CPR for streptococcal pharyngitis predicted accurately the probability of a positive culture in our diverse population (area under the receiver operating characteristic curve, 0.71) . The simplified CPR also showed clinically useful likelihood ratios and posterior probabilities . CONCLUSION: A simplified version of the Walsh CPR is accurate for diagnosing streptococcal pharyngitis in an inner-city population . This finding should provide clinicians more confidence in applying the CPR in similar clinical settings.

Zh Mikrobiol Epidemiol Immunobiol, 2003 Jan-Feb, (1), 14 - 7
{Biliary microflora of patients with chronic pancreatitis}; Savitskaia KI et al.; Data on the contamination of bile specimens (1997 and 2001, 205 specimens, 137 cultures), examined in the Laboratory of Clinical Microbiology of the Vladimirsky Regional Research Clinical Institute, as well as data on the microflora composition in 40 specimens of bile, obtained from patients with clinically diagnosed chronic pancreatitis at the stage of exacerbation, are presented . Out of 40 specimens of bile 54 cultures of microorganisms were isolated; of these, 33.3% were bacteria of the genus Staphylococcus, Gram negative bacilli took the second place in occurrence (27.8%) and the third place belonged to bacteria of the genus Streptococcus (18.5%) . The antibiotic sensitivity of the isolated microorganisms is characterized.

Curr Opin Drug Discov Devel, 2002 Sep, 5(5), 785 - 92
Novel approaches to antimicrobial therapy: peptide deformylase; Waller AS et al.; Peptide deformylase (PDF) represents one of the most exciting new targets for the development of novel antimicrobial chemotherapies . PDF is an essential bacterial metalloenzyme that deformylates the N-formylmethionine of newly synthesized bacterial polypeptides . Recent progress in understanding the structure and function of PDF has greatly facilitated the drug discovery process . In this article, the potential of PDF as an antimicrobial target is reviewed, and progress in the development of PDF inhibitors (PDFIs) is highlighted . Several structural classes of compounds have been reported as inhibitors of PDF . However, the real challenge has been in obtaining molecules with potent in vivo antibacterial activity against a range of drug-resistant pathogens . One of the more encouraging compounds reported, BB-83698 (British Biotech plc/Genesoft Inc), has shown in vivo efficacy against Streptococcus pneumoniae in both mouse thigh and lung infection models at doses equivalent to existing therapies . The published data suggest that PDFIs are a promising new class of antimicrobial agent best suited to treat respiratory tract infections (RTIs), but with the potential for activity against a variety of other pathogens . It is anticipated that the first PDFI targeting RTIs will enter the clinic soon.

MCN Am J Matern Child Nurs, 2003 Mar-Apr, 28(2), 106 - 10
The relationship between abuse, sexually transmitted diseases, & group B streptococcus in childbearing women; Winn N et al.; PURPOSE: To examine the relationship between abuse, sexually transmitted diseases (STDs) and group B (GBS) infection among childbearing women using Selye's (1978) stress response theory . DESIGN AND METHODS: Retrospective chart review (n = 205) from two different clinical sites in Washington State, using the Childbearing Health Questionnaire to guide data collection . The women in the sample had an average age of 26.4 years and represented Anglo (81.4%), Hispanic (12%), Native American (3.9%), and African American (2.5%) ethnic groups . Thirty-eight percent ( = 78) reported experiencing physical and/or sexual abuse during their lifetimes and 31% had been diagnosed with an STD . RESULTS: Abuse was significantly related to STDs, and ethnicity emerged as a significant variable for the Hispanic women participating in this study . Findings indicated that infection with group B was also related to abuse status ( r=.60, p < or =.002) and to presence of herpes simplex virus-2 (r =.468, p<or =.01) . Total prevalence of STDs was positively related to abuse ( r=.78, p <or =.000) . Abused Hispanic women were more likely to be positive for STDs than were their nonabused counterparts ( p <or =.03) . CLINICAL IMPLICATIONS: The findings support previously published results that abuse is widespread in the United States and that abused women are at increased risk for STDs . These results highlight the need for regular screenings for abuse during healthcare, for abuse is a critical variable to consider when screening for STDs and GBS . STD screening typically occurs during the first prenatal visit and may need to be repeated for high-risk groups.

Dent Mater, 2003 May, 19(3), 212 - 7
Zinc sulfate addition to glass-ionomer-based cements: influence on physical and antibacterial properties, zinc and fluoride release; Osinaga PW et al.; OBJECTIVES: The aim of this study is to evaluate the effect of ZnSO(4) addition to a conventional glass ionomer and a resin-modified glass ionomer on solubility, flexural strength, zinc and fluoride (F) release, and Streptococcus mutans growth inhibition . METHODS: 5 or 10% ZnSO(4) was added to Vitremer and Ketac-Fil powders . Solubility test was performed based on ISO 7489 . Flexural strength was determined by 3-point bending test based on ISO 4049 . Zn release/uptake was determined by atomic emission spectrometry; F release/uptake was measured using a F-specific electrode . Both release measurements were performed for 15 d before and 15 d after recharging . Antibacterial test was conducted according to agar plate methods against S . mutans, by measuring the inhibition halos in 1-h and 15-d specimens . Data were analyzed by ANOVA . RESULTS: Solubility increased with higher ZnSO(4) content, but remained below the ISO 7489 limit . Flexural strength was not affected by ZnSO(4) addition, and Vitremer performed better than Ketac-Fil . The control materials released no zinc . Vitremer with 10% ZnSO(4) released the highest amount of zinc . Fluoride release was similar for Ketac-Fil and Vitremer . In both cases, the highest amounts were released in the first 24 h . The growth inhibition halo of S . mutans was similar for both materials with highest content of ZnSO(4) and occurred only with 1-h specimens . SIGNIFICANCE: Zinc addition decreased microorganisms growth and improved fluoride release, without significantly affecting the materials' flexural strength and solubility.

Fitoterapia, 2003 Feb, 74(1-2), 139 - 43
Evaluation of the anti-microbial and anti-inflammatory activities of the medicinal plants Dodonaea viscosa, Rumex nervosus and Rumex abyssinicus; Getie M et al.; The crude extracts of the leaves of Dodonaea viscosa and Rumex nervosus as well as of the root of Rumex abyssinicus were tested for anti-microbial and anti-inflammatory activities . It was observed that the three plants possess antibacterial activity against Streptococcus pyogenes and Staphylococcus aureus and strong activity against Coxsackie virus B3 and influenza A virus . In contrast, none of them exhibited anti-fungal activity . The anti-inflammatory activity test results verified that only R . abyssinicus inhibited the synthesis of prostaglandin (PG) E(2).

Pharmacotherapy, 2003 Mar, 23(3), 349 - 59
Health care resource utilization associated with treatment of penicillin-susceptible and -nonsusceptible isolates of Streptococcus pneumoniae; Klepser ME et al.; Despite failure to correlate in vitro susceptibility with clinical outcomes for respiratory tract infections and bacteremia, resistance affects management of patients with pneumococcal infections . The economic impact of resistance among pneumococci has not been evaluated . We conducted a single-center, retrospective, observational, cohort study of hospitalized patients infected with Streptococcus pneumoniae isolated from blood or a respiratory source between January 1, 1995, and December 31, 1998 . Data were collected for 36 days surrounding the day that the first positive culture was collected . Patients were grouped according to isolate penicillin-susceptibility profile {susceptible minimum inhibitory concentration (MIC) < or = 0.06 microg/ml, nonsusceptible MIC > or = 0.125 microg/ml), and data were analyzed with respect to health care resource utilization patterns . Of 231 patients identified, 142 and 89 had susceptible and nonsusceptible isolates, respectively . Groups were similar with respect to demographics and comorbidities, except that patients infected with a nonsusceptible isolate were more likely to have the isolate obtained from a respiratory source and to have a history of recent antibiotic therapy . No difference was noted with respect to clinical outcome; however, patients infected with a nonsusceptible isolate had a longer median stay (14 vs 10 days, p<0.05) . They also had significantly higher total median costs (1600 dollars, 95% confidence interval 257-2943 dollars) due to room and nursing services . Infections caused by penicillin-nonsusceptible pneumococci were not associated with a worse outcome in hospitalized patients but were associated with increased cost of care.

Pediatr Dent, 2003 Jan-Feb, 25(1), 43 - 8
Surface antibacterial properties of fissure sealants; Matalon S et al.; PURPOSE: Sealants form a physical barrier between the oral environment and deep fissures that contribute to caries prevention . It is postulated that sealants possessing antibacterial properties are advantageous . The purpose of this study was to evaluate the antibacterial properties of four pit and fissure sealants using direct contact test (DCT) and agar diffusion test (ADT) . METHODS: For the DCT, 8 samples of Helioseal F (Vivadent), Ultraseal XT (Ultadent-Weldent), Conseal F (SDI), and Dyract Seal (Dentsply) were placed on the sidewalls of wells of a 96-microtiter plate . After polymerization, freshly grown Streptococcus mutans cells (circa 1 x 10(6)) were placed on the surface of each sample for 1 hour at 37 degrees C . Fresh media was then added to each well and bacterial growth was followed for 16 hours by temperature-controlled spectrophotometer . Similarly prepared samples were aged in phosphate buffered saline for 14 and 30 days and the DCT was repeated . The ADT was performed by placing samples in uniform wells punched in agar plates . RESULTS: Freshly polymerized samples in the DCT, Dyract Seal and Ultraseal XT possessed prominent antibacterial properties . Dyract Seal also demonstrated the most potent antibacterial properties, which lasted 14 days but faded within 30 days . In ADT, the halo in the bacterial lawn was measured after 48 hours, and only Dyract Seal demonstrated an inhibition zone . CONCLUSIONS: The compomer-based sealant Dyract Seal possessed the most potent and longest lasting antibacterial activity.

Lasers Med Sci, 2003, 18(1), 51 - 5
Bactericidal effects of different laser wavelengths on periodontopathic germs in photodynamic therapy; Chan Y et al.; This study was an attempt to clarify whether the bactericidal effects of photodynamic therapy (PDT) are wavelength or dose-dependent . We also attempted to create an optimised protocol for a light-based bactericidal modality to eliminate periodontal pathogens . Cultures of Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, Porphromonas gingivalis, Prevotella intermedia, and Streptococcus sanguis, were exposed to a He-Ne laser (632.8 nm) with a 30 mW power output, a 100 mW diode laser at 665 nm, or a 100 mW diode laser at 830 nm, in the presence or absence of methylene blue (MB) as a photosensitiser . A control group was also used with exposure to MB alone without laser exposure . The cultures were analysed by viable counts . The results indicated that exposure to the 100 mW laser light could eliminate up to 40% of bacteria on average . In particular, the most effective killing occurred with exposure to laser light in combination with the MB photosensitiser . The results of kinetic studies indicated that the best PDT response rate was achieved with a 60 s (energy density 21.2 J/cm(2)) exposure to the 665 nm wavelength diode laser in the presence photosensitiser . In this condition, approximately 95% of A . actinomycetemcomitans and F . nucleatum, and 99-100% of the black-pigmented bacteria ( P . gingivalis and P . intermedia) and S . sanguis were eliminated . These results showed that both wavelength and energy density are important factors, and that a low power laser of optimal wavelength and dosage, in combination with an appropriate photosensitiser, is a practical bactericidal modality . We concluded that using a diode laser of proper power and wavelength to deliver 60 s of irradiation could be a useful adjunct with mechanical debridement in the prevention of the re-colonisation of subgingival lesions by pathogenic microorganisms.

Nat Med, 2003 Apr, 9(4), 424 - 30 Epub 2003 Mar 10.
Geographic diversity and temporal trends of antimicrobial resistance in Streptococcus pneumoniae in the United States; McCormick AW et al.; Resistance of Streptococcus pneumoniae to antibiotics is increasing throughout the United States, with substantial variation among geographic regions . We show that patterns of geographic variation are best explained by the intensity of selection for resistance, which is reflected by differences between the proportions of resistance within individual serotypes, rather than by differences between the frequencies of particular serotypes . Using a mathematical transmission model, we analyzed temporal trends in the proportions of singly and dually resistant organisms and found that pneumococcal strains resistant to both penicillin and erythromycin are increasing faster than strains singly resistant to either . Using the model, we predict that by 1 July 2004, in the absence of a vaccine, 41% of pneumococci at the Centers for Disease Control and Prevention (CDC)'s Active Bacterial Core surveillance (ABCs) sites, taken together, will be dually resistant, with 5% resistant to penicillin only and 5% to erythromycin only.

Clin Diagn Lab Immunol, 2003 Mar, 10(2), 246 - 51
Inhibition of pneumococcal adherence to human nasopharyngeal epithelial cells by anti-PsaA antibodies; Romero-Steiner S et al.; The role of pneumococcal (Pnc) surface adhesin A (PsaA) in the adherence of Streptococcus pneumoniae (pneumococcus) to host cells is not well defined . We examined the effect of anti-PsaA antibodies in an inhibition of adherence assay using Detroit 562 nasopharyngeal human epithelial cells . Rabbit polyclonal (Pab) anti-recombinant PsaA (rPsaA) sera, a purified mouse monoclonal antibody (MAb) (MAb 6F62G8E12), and 22 healthy adult sera with known anti-PsaA IgG levels (obtained by enzyme-linked immunosorbent assay) were evaluated for their abilities to inhibit Pnc adherence to confluent monolayers (measured as percent reduction in CFU counts compared to those of uninhibited controls) . Pnc adherence was dependent on capsular phenotype (no or low adherence for opaque strains) . With an inoculum of 10(4) to 10(5) bacteria/well, the mean +/- standard deviation count in controls was 163 +/- 32 CFU/well for transparent strains . Low adherence was observed for a PsaA-minus mutant even at higher inoculum doses . Mean percent inhibitions of adherence with Pab and MAb were 54 and 50%, respectively . Adult sera showed inhibition in a dose-response fashion with a range of 98 to 8%, depending on the serum anti-PsaA antibody concentration . Absorption of Pab with rPsaA restored Pnc adherence to control levels . Absorption of sera with a PsaA-minus mutant did not result in a significant decrease (P >0.05) of inhibition of adherence activity . Additionally, nearly 100% of Pnc adherence was inhibited by lipidated rPsaA at 2.5 micro g/ml . Our data support the argument that PsaA is an adhesin that mediates Pnc adherence to human nasopharyngeal cells . This functional assay may be useful in evaluating antibodies elicited in response to PsaA vaccination.

Microbiology, 2003 Feb, 149(Pt 2), 497 - 504
Spontaneous sequence duplications within capsule genes cap8E and tts control phase variation in Streptococcus pneumoniae serotypes 8 and 37; Waite RD et al.; Capsule phase variants were isolated from serotype 8 and serotype 37 pneumococcal sorbarods . Sequence duplications within the essential capsule genes - cap8E (type 8) and tts (type 37) - were found to introduce frameshifts and generate acapsular phenotypes . Capsular revertants possessed wild-type cap8E and tts genes, indicating the precise excision of these duplications . Reversion frequencies (OFF-ON) fit a linear relationship between log(frequency of reversion) and log(length of duplication), previously found for serotype three pneumococci {Waite, R . D., Struthers, J . K . & Dowson, C . G . (2001) . Mol Microbiol 42, 1223-1232} . This study provides evidence that capsule phase variation can occur in pneumococcal serotypes with either simple (one to three genes) or complex capsule-encoding loci (12 genes) . Given the key role of CapE (the first monosaccharide transferase) in other clinically important pneumococci, such as serotypes 14 and 19F with complex capsular loci, the observed duplication within cap8E suggests that capsule phase variation could be controlled by tandem sequence duplication in capE homologues in other pneumococcal serotypes that construct their capsules through polymerization of lipid-linked intermediates.

Microbiology, 2003 Feb, 149(Pt 2), 407 - 17
Role of the Streptococcus agalactiae ClpP serine protease in heat-induced stress defence and growth arrest; Nair S et al.; The main causes of microbial death after heat exposure are not well understood . Here, it is shown that the heat-shock protein ClpP plays a major role in heat-induced growth arrest in Streptococcus agalactiae . A mutant lacking the ClpP protease was more sensitive to the inhibitory effects of heat, salt and oxidative stress than the isogenic wild-type strain . During growth arrest, this mutant displayed important modifications of its total protein content, including a decreased level of essential metabolic enzymes such as the alcohol dehydrogenase . Analysis of protein carbonylation demonstrated that the ClpP protease plays a role in preventing accelerated protein oxidation . Higher levels of oxidized DnaK, a key modulator of the heat-shock regulon, were observed in the ClpP mutant and these were increased following heat shock . Accumulation of oxidized/inactivated DnaK might explain why the ClpP mutant was unable to properly synthesize DNA and proteins, and why it exhibited an aberrant cell morphology . Even though ClpP plays a minor role in the virulence of S . agalactiae in a murine infection model, the data presented here point to the importance of ClpP in oxidative stress defence in preventing heat-induced cell alterations.

Microbiology, 2003 Feb, 149(Pt 2), 399 - 406
An amino acid change near the carboxyl terminus of the Streptococcus gordonii regulatory protein Rgg affects its abilities to bind DNA and influence expression of the glucosyltransferase gene gtfG; Vickerman MM et al.; The Streptococcus gordonii glucosyltransferase structural gene, gtfG, is located immediately downstream from its positive transcriptional regulatory determinant, rgg . Recent genetic studies have indicated that the 3' end of rgg is involved either directly as a binding site or indirectly, e.g . by playing a role in secondary structure, in the interaction of Rgg with the gtfG promoter . A previously identified spontaneous mutant with a point mutation near the 3' end of rgg had only approximately 25% of the parental level of glucosyltransferase activity . To determine if this decreased activity was due to a change in the DNA binding site of trans-acting Rgg, or due to a change in the Rgg protein itself, complementation analyses and DNA-binding studies were performed . In Rgg-deficient strains, the chromosomal rgg point mutation did not influence the ability of plasmid-borne rgg to increase glucosyltransferase expression . However, plasmids carrying parental rgg were able to increase glucosyltransferase activity and expression of a gtfG promoter fusion to a greater extent than plasmids carrying the mutant allele, indicating that the mutant Rgg protein had decreased activity . The ability of NH(2)-terminal (hexahistidine) tagged proteins to bind to a 107 bp dsDNA fragment corresponding to the region immediately upstream of gtfG was demonstrated by surface plasmon resonance . Despite their differences in activity, both mutant and parental recombinant Rgg proteins bound to this dsDNA, albeit with different strengths . These studies provide insights into functional domains of S . gordonii Rgg which influence glucosyltransferase expression, and may have implications for Rgg-like regulatory proteins in related bacteria.

J Clin Microbiol, 2003 Mar, 41(3), 1307 - 10
emm Gene distribution among erythromycin-resistant and -susceptible Italian isolates of Streptococcus pyogenes; Zampaloni C et al.; The phenotypes and genetic determinants for macrolide resistance were determined for 167 erythromycin-resistant Streptococcus pyogenes strains . A cMLS phenotype was shown in 18% of the erythromycin-resistant strains, while inducible resistance was apparent in 31% and the M phenotype was apparent in 50% . The emm gene type of this set of resistant isolates and that of 48 erythromycin-sensitive isolates were determined . emm2 and emm48 were recorded only in the resistant strains of the M phenotype, while approximately all of the strains harboring the emm22 gene had the cMLS phenotype . More than 80% of the emm89-positive strains had the iMLS phenotype, and the same portion of emm4 strains presented the M phenotype . emm3 is recorded only among sensitive strains . The distribution of frequencies of the genetic determinant for the virulence factor M protein was significantly different both among organisms of different types of resistance and between resistant and sensitive populations of S . pyogenes under study.

J Clin Microbiol, 2003 Mar, 41(3), 1004 - 9
Invasive Streptococcus iniae infections outside North America; Lau SK et al.; Streptococcus iniae, a fish pathogen causing infections in aquaculture farms worldwide, has only been reported to cause human infections in North America . In this article, we report the first two cases of invasive S . iniae infections in two Chinese patients outside North America . While the first patient presented with bacteremic cellulitis, which is the most common presentation in previous cases, the second patient represents the first recognized case of S . iniae osteomyelitis . Both S . iniae strains isolated from the two patients were either misidentified or unidentified by three commercial systems and were only identified by 16S rRNA gene sequencing . Since no currently available commercial system for bacterial identification includes S . iniae in its database, 16S rRNA gene sequencing is the most practical and reliable method to identify the bacterium at the moment . In contrast to the distinct genetic profile described previously in clinical isolates from Canada, the present two isolates and a clinical isolate from a Canadian patient were found to be genetically unrelated, as demonstrated by pulsed-field gel electrophoresis . Morphologically, colonies of both isolates were also larger, more beta-hemolytic and mucoid, which differ from the usual morphotype described for S . iniae . Owing to their habit of cooking and eating fresh fish, the Asian population is strongly associated with S . iniae infections . As a result of the difficulty in making microbiological diagnosis in patients with cellulitis and the problem of identification in most clinical microbiology laboratories, the prevalence of S . iniae infections, especially in the Asian population, may have been under-estimated.

Ophthalmology, 2003 Mar, 110(3), 569 - 74
Bilateral cavernous sinus thromboses and intraorbital abscesses secondary to Streptococcus milleri; Watkins LM et al.; PURPOSE: To report the first case of bilateral cavernous sinus thromboses and bilateral intraorbital abscesses secondary to Streptococcus milleri . STUDY DESIGN: Single interventional case report . INTERVENTION AND TESTING: The findings of the ophthalmic evaluation, radiographic imaging, medical and surgical intervention, specimen cultures, and clinical course were analyzed . RESULTS: A 17-year-old female had bilateral proptosis, decreased vision in the left eye, and altered mental status at presentation . An orbital compartment syndrome developed in the left eye and purulent material was present after lateral canthotomy, suggestive of an intraorbital abscess . Magnetic resonance imaging (MRI) scans revealed bilateral cavernous sinus thromboses, and subsequent computed tomographic (CT) scans revealed bilateral intraorbital abscesses in the setting of acute ethmoid and sphenoid sinusitis . Antibiotic treatment and surgical drainage of the orbital abscess and sinuses was performed, and specimen cultures revealed S . milleri . After surgery, the patient experienced hearing loss and a right internal capsule infarct, in addition to complete vision loss in the left eye . A second intraorbital abscess developed in the right eye and was drained surgically . The vision remained 20/20 . CONCLUSIONS: Streptococcus milleri is a virulent organism with a propensity to form abscesses in multiple areas of the body and should be considered as a possible etiologic agent in abscess formation of the orbit and cavernous sinus thrombosis.

Mol Microbiol, 2003 Mar, 47(6), 1589 - 99
Streptococcus dysgalactiae-derived mitogen (SDM), a novel bacterial superantigen: characterization of its biological activity and predicted tertiary structure; Miyoshi-Akiyama T et al.; A mitogenic substance, designated Streptococcus dysgalactiae-derived mitogen (SDM), was purified from S . dysgalactiae culture supernatant, and the gene encoding the mitogen was cloned . Both native and recombinant SDM expressed in Escherichia coli significantly activated human V beta 1+ and V beta 23+ T cells in association with major histocompatibility complex (MHC) class II molecules on accessory cells, indicating that SDM possesses superantigenic properties . The sdm gene consists of two segments encoding a signal peptide and a mature 25 kDa protein composed of 212 amino acids . Three of 34 S . dysgalactiae strains but none of 28 Streptococcus pyogenes strains examined carried sdm . Phylogenetic analysis indicated that SDM belongs to a family distinct from established bacterial superantigens . SDM showed around 30% homology with other superantigens at the amino acid sequence level . The tertiary structure of SDM was predicted by modelling onto streptococcal pyrogenic exotoxin C and streptococcal mitogenic exotoxin Z-2, both of which share highly homologous structure-determining regions . SDM showed overall structural similarity to both these superantigens . This is the first study to characterize fully a bacterial superantigen from S . dysgalactiae.

Ned Tijdschr Geneeskd, 2003 Feb 8, 147(6), 225 - 9
{Three toddlers with a swelling in the neck}; Gerrits JA et al.; Three children, a girl aged 2.5 years and two boys aged 2 and 3 years respectively, presented with unilateral cervical lymphadenitis . The first patient had acute bacterial lymphadenitis due to group A Streptococcus, characterised by a painful cervical swelling of acute onset . The second patient had painless cervical lymphadenitis caused by Mycobacterium avium-intracellulare, which drained spontaneously . The third patient developed a non-tender, cervical swelling within a day . He too was systemically ill with fever and a headache . The lymphadenitis was caused by Bartonella henselae . After drainage, dissection and/or antibiotic therapy, all three recovered . A cervical mass in a young child is most frequently caused by an infectious lymphadenopathy . It rarely represents a malignant or other systemic disease . In many cases the diagnosis of infectious lymphadenitis can be made on the basis of the case history and clinical characteristics . However, when malignancy cannot be excluded tissue examination is always indicated.

J Reprod Med, 2003 Feb, 48(2), 107 - 11
Limitations of the obstetric group B Streptococcus protocol; Nemunaitis-Keller J et al.; OBJECTIVE: To assess compliance with the Centers for Disease Control and Prevention (CDC) screening-based protocol for obstetric group B Streptococcus (GBS) and to determine an acceptable threshold for protocol failure . STUDY DESIGN: A retrospective chart review was carried out for all deliveries performed through the resident-run community clinic from January through June 1999 . Compliance with the CDC protocol was assessed by reviewing collected data from patient charts and comparing it to CDC requirements . Data were collected regarding patient demographics, antenatal GBS status, gestational age at screening, time of rupture of the membranes, time the antibiotic was given and time of delivery . RESULTS: A total of 248 charts were reviewed . Elective cesarean deliveries were excluded (25 charts) . Unknown culture status was found for 22 (9.9%) patients . Cultures were collected before 35 weeks' gestation in 39 (17.5%) patients and at > 37 weeks' gestation in 28 (12.6%) patients . Of those with known positive GBS status, 4 (7.0%) were not treated, and antibiotics were given less than four hours before delivery in 13 (24.5%) patients . Of those with unknown status, six (27.2%) were not treated . Overall, there was 70% compliance with the culture collection arm of the protocol and 87% compliance with the treatment arm . CONCLUSION: Fulfillment of CDC guidelines in this community setting is imperfect . There are several areas beyond physician control, including precipitous delivery and patient non-compliance . However, perhaps an acceptable threshold for limitations of adherence to the protocol can be reached.

Jpn J Antibiot, 2002 Dec, 55(6), 697 - 729
{Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents . Special references to bacteria isolated between April 1999 and March 2000}; Mashita K et al.; The annual multicenter studies on isolated bacteria from infections in general surgery and their antimicrobial susceptibility have been conducted in Japan since July 1982 . In this paper, the results obtained in the academic year 1999 (from April 1999 to March 2000) have been summarized . Two hundred seven cases were investigated, and 411 strains were isolated from 169 cases (81.6%) . Of those strains, 184 and 227 strains were from primary infections and postoperative infections, respectively . In primary infections, the isolation rates of anaerobes, Streptococcus spp., and Escherichia coli were higher than in postoperative infections, while in postoperative infections, those of Gram-positive aerobes were higher than in primary infections . Staphylococcus aureus were most frequently isolated among Gram-positive aerobes, Peptostreptococcus prevotii among Gram-positive anaerobes, E . coli among Gram-negative aerobes, and Bacteroides fragilis among Gram-negative anaerobes . In primary infections, the percentage of Gram-negative aerobes, which gradually increased by the year 1998, decreased in the year 1999 . The percentage of Gram-negative anaerobes increased, while that of Gram-negative bacteria was equivalent to that in the last year . In postoperative infections, the percentage of Gram-negative anaerobes, which continuously increased after the year 1990, decreased, while that of Gram-positive aerobes, which decreased in the last year, increased . Methicillin-resistant S . aureus accounted for 70.7% of S . aureus (41 strains) . Either the number of strain or the percentage of MRSA decreased . The susceptibilities of E . coli and Klebsiella pneumoniae decreased against third and forth generation cephems, oxacephems, and monobactams . The susceptibilities of P . aeruginosa to carbapenems tend to decrease after the year 1997 . S . aureus showed good susceptibilities to the tested drugs including arbekacin, vancomycin, and teicoplanin.

Rapid Commun Mass Spectrom, 2003, 17(6), 576 - 82
Identification of hyaluronic acid oligosaccharides by direct coupling of capillary electrophoresis with electrospray ion trap mass spectrometry; Kuhn AV et al.; A new method for the identification of oligosaccharides obtained by enzymatic digestion of hyaluronic acid (HA) with bacterial hyaluronidase (HA lyase, E.C . 4.2.2.1, from Streptococcus agalactiae) using online capillary electrophoresis/electrospray mass spectrometry (CE/ESI-MS) is presented . A fused-silica capillary coated with polyacrylamide was used with a 40 mM ammonium acetate buffer at pH 9.0 and a separation voltage of +30 kV applied to the inlet . Separation was achieved for oligosaccharides containing 4-16 monomers . The migration behavior follows the chain length of the oligomers, regardless of charge state . However, no linear relationship was found for the relation between mobility and chain length . Using an ion trap mass analyzer, complementary structural information was obtained by MS/MS and MS(n) experiments .

J Med Microbiol, 2003 Mar, 52(Pt 3), 251 - 8
Antimicrobial susceptibility patterns and genomic diversity in strains of Streptococcus pyogenes isolated in 1978-1997 in different Brazilian cities; de Melo MC et al.; Penicillin has been the antimicrobial of choice for the treatment of Streptococcus pyogenes infections for almost six decades . Although penicillin-resistant isolates have not been described to date, clinical failures have been reported after treatment with beta-lactams . In this study, we analysed the antimicrobial susceptibility and genetic diversity of S . pyogenes isolates obtained from healthy carriers or patients in different cities in the south and south east of Brazil . The MICs were determined for penicillin and seven other antimicrobials . Penicillin tolerance was also investigated . Genetic diversity was analysed by PFGE after SmaI fragmentation of the genomic DNA . All 211 isolates tested were susceptible to penicillin (MIC 0.0025-0.02 mg l(-1)) . Four isolates were moderately penicillin-tolerant (MBC/MIC = 16 mg l(-1)) . Most of the other drugs tested were very active against the strains examined, except for tetracycline, to which 50 % of strains were resistant . We also found extensive genetic diversity, in that 60 different patterns were recognized in the 96 strains studied . Indeed, we found no correlation between tetracycline resistance and clonality . Despite this diversity, some PFGE patterns persisted for up to 18 years and specific clone types were spread over different geographical locations

J Biol Chem, 2003 May 9, 278(19), 17336 - 43 Epub 2003 Mar 05.
Maturation processing and characterization of streptopain; Chen CY et al.; Streptopain is a cysteine protease expressed by Streptococcus pyogenes . To study the maturation mechanism of streptopain, wild-type and Q186N, C192S, H340R, N356D and W357A mutant proteins were expressed in Escherichia coli and purified to homogeneity . Proteolytic analyses showed that the maturation of prostreptococcal pyrogenic exotoxin B zymogen (pro-SPE B) involves eight intermediates with a combination of cis- and trans-processing . Based on the sequences of these intermediates, the substrate specificity of streptopain favors a hydrophobic residue at the P2 site . The relative autocatalytic rates of these mutants exhibited the order Q186N > W357A > N356D, C192S, H340R . Interestingly, the N356D mutant containing protease activity could not be converted into the 28-kDa form by autoprocessing . This observation suggested that Asn(356) might involve the cis-processing of the propeptide . In addition, the maturation rates of pro-SPE B with trypsin and plasmin were 10- and 60-fold slower than that with active mature streptopain . These findings indicate that active mature streptopain likely plays the most important role in the maturation of pro-SPE B under physiological conditions.

J Biol Chem, 2003 May 9, 278(19), 16561 - 6 Epub 2003 Mar 05.
SIC, a secreted protein of Streptococcus pyogenes that inactivates antibacterial peptides; Frick IM et al.; Some isolates of the significant human pathogen Streptococcus pyogenes, including virulent strains of the M1 serotype, secrete protein SIC . This molecule, secreted in large quantities, interferes with complement function . As a result of natural selection, SIC shows a high degree of variation . Here we provide a plausible explanation for this variation and the fact that strains of the M1 serotype are the most frequent cause of severe invasive S . pyogenes infections . Thus, protein SIC was found to inactivate human neutrophil alpha-defensin and LL-37, two major antibacterial peptides involved in bacterial clearance . This inactivation protected S . pyogenes against the antibacterial effect of the peptides . Moreover, SIC isolated from S . pyogenes of the M1 serotype was more powerful in this respect than SIC variants from strains of M serotypes 12 and 55, serotypes rarely connected with invasive infections.

FEMS Microbiol Lett, 2003 Feb 28, 219(2), 209 - 14
Development of PCR assays for detection of Streptococcus canis; Hassan AA et al.; Streptococcus canis isolates, also including S . canis of artificially contaminated milk, could be identified by polymerase chain reaction (PCR) amplification using oligonucleotide primers designed according to species-specific parts of the 16S rRNA gene and, after sequencing, according to S . canis-specific parts of the 16S-23S rDNA intergenic spacer region and with oligonucleotide primers detecting an internal fragment of the group G streptococcal CAMP factor gene cfg . The 16S rRNA gene- and CAMP factor gene cfg-specific oligonucleotide primers could be used together in a multiplex PCR . No cross-reactivities could be observed with other group G streptococcal isolates or with any of the other control strains of various streptococcal species and serogroups . The PCR methods presented in this study allowed a rapid and reliable identification of S . canis and might help to improve the diagnosis of this bacterial species in animal and human infections.

FEMS Microbiol Lett, 2003 Feb 28, 219(2), 195 - 201
Allelic variation in srtAs of Streptococcus suis strains; Osaki M et al.; Streptococcus suis NCTC10234 possesses five srtA homologs: srtA encodes sortase, which anchors surface proteins with an LPXTG motif to the cell wall, while the functions of the other four homologs (the srtBCD cluster and srtE) remain unknown . The genetic organization of the srtA region was found to be conserved in the 59 S . suis strains examined in this study . Although the srtAs in three of these strains showed strong sequence divergence, their functions were verified to be overlapping by genetic complementation, indicating the functional conservation of srtAs during the evolution of these strains . These results indicate the importance of an srtA-mediated cell wall sorting system for displaying proteins on the surface of S . suis.

Microb Pathog, 2003 Jan, 34(1), 27 - 37
Role of suilysin in pathogenesis of Streptococcus suis capsular serotype 2; Lun S et al.; Three suilysin (SLY) knockout mutant strains of Streptococcus suis serotype 2 were generated by allelic replacement from one North American and two European wild type strains . The mutants were characterized by Southern blot, Western blot and phenotyping . In vitro bactericidal testing showed that both wild type and SLY mutants were resistant to bactericidal factors in whole pig blood . To demonstrate the role of SLY during S . suis infection, four animal trials were carried out using young pigs . Either high dose (4 x 10(6)CFU/ml/pig) or low dose (0.5 x 10(6)CFU/ml/pig) live cell aerosol was applied to the pharynx . In one trial, a low challenge dose of North American strain SX332 and its isogenic sly(-) mutant strain (SX932) resulted in acute disease in 3/5 of pigs exposed to the wild type strain, while 5/5 of pigs exposed to the mutant strain survived the trial . In the repeat trial, 1/8 of pigs in wild type group and 6/8 of pigs in mutant group developed disease . The high dose trial with 332/932 pair showed that 4/8 pigs challenged with wild type and 5/8 of pigs challenged with mutant strain developed disease respectively . The third low dose trial, using European strain 31533 and its isogenic sly(-) mutant strain SX911, showed that 1/8 of pigs challenged with the wild type strain and 4/8 of pigs challenged with the corresponding mutant strain developed disease . All the diseased pigs showed fever, clinical signs and developed septicemia . S . suis was isolated from tissue samples such as brain, submandibular lymph node, lung, spleen, liver, heart or joint . Serum antibody titer against cell surface proteins changed little while the antibody titer against SLY increased only in the wild type group after challenge . sly gene was cloned and expressed in E . coli . The recombinant SLY (rSLY) protein showed 800 hemolysin units per microg protein . In vitro study showed that rSLY triggered TNFalpha production by human monocytes and IL-6 production by pig pulmonary alveolar macrophages and monocytes . Thus, the results of this study suggest that SLY does not seem to be a critical virulence factor for S . suis serotype 2 respiratory infection, but by stimulating cytokine release it may play a role in innate immunity.

J Med Chem, 2003 Mar 13, 46(6), 1005 - 15
Synthesis and structure-activity relationships of 5-amino-6-fluoro-1-{(1R,2S)-2-fluorocyclopropan-1-yl}-8-methylquinolonecarboxylic acid antibacterials having fluorinated 7-{(3R)-3-(1-aminocyclopropan-1-yl)pyrrolidin-1-yl} substituents; Inagaki H et al.; A series of novel 5-amino-6-fluoro-1-{(1R,2S)-2-fluorocyclopropan-1-yl}-8-methylquinolones bearing fluorinated (3R)-3-(1-aminocyclopropan-1-yl)pyrrolidin-1-yl substituents at the C-7 position (2-4) was synthesized to obtain potent drugs for infections caused by Gram-positive pathogens, which include resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), and vancomycin-resistant enterococci (VRE) . These fluorinated compounds 2-4 exhibited potent antibacterial activity comparable with that of a compound bearing a non-fluorinated (3R)-3-(1-aminocyclopropan-1-yl)pyrrolidine moiety at the C-7 position (1) and had at least 4 times more potent activity against representative Gram-positive bacteria than ciprofloxacin (CPFX), gatifloxacin (GFLX), or moxifloxacin (MFLX) . Among them, the 7-{(3S,4R)-4-(1-aminocyclopropan-1-yl)-3-fluoropyrrolidin-1-yl} derivative 3 (=DQ-113), which showed favorable profiles in preliminary toxicological and nonclinical pharmcokinetic studies, exhibited potent antibacterial activity against clinically isolated resistant Gram-positive pathogens.

J Bacteriol, 2003 Mar, 185(6), 2051 - 8
Characterization of a novel fucose-regulated promoter (PfcsK) suitable for gene essentiality and antibacterial mode-of-action studies in Streptococcus pneumoniae; Chan PF et al.; The promoter of the Streptococcus pneumoniae putative fuculose kinase gene (fcsK), the first gene of a novel fucose utilization operon, is induced by fucose and repressed by glucose or sucrose . When the streptococcal polypeptide deformylase (PDF) gene (def1, encoding PDF) was placed under the control of P(fcsK), fucose-dependent growth of the S . pneumoniae (P(fcsK)::def1) strain was observed, confirming the essential nature of PDF in this organism . The mode of antibacterial action of actinonin, a known PDF inhibitor, was also confirmed with this strain . The endogenous fuculose kinase promoter is a tightly regulated, titratable promoter which will be useful for target validation and for confirmation of the mode of action of novel antibacterial drugs in S . pneumoniae.

J Bacteriol, 2003 Mar, 185(6), 1857 - 69
Novel genomic rearrangement that affects expression of the Streptococcus pyogenes streptolysin O (slo) gene; Savic DJ et al.; A RecA-independent chromosomal rearrangement in the upstream region of the streptolysin O (slo) gene of Streptococcus pyogenes which affects slo expression was identified . PCR analysis was used to demonstrate that this kind of rearrangement was found in several strains of different lineages . Chromosomal loci involved in the recombination were found to be 746 kb apart on the 1.85-Mb-long chromosome . The primary structure of the splicing region, the reproducibility of the rearrangement, and the fact that reconstructed recombinant molecules fused to erm and lacZ reporter genes affected their expression indicate that this event is not accidental but may play a role in the expression of the slo gene . In addition, the product of the recombining DNAs, including the splicing site, does not follow any example of a known recombination mechanism . The implications of this rearrangement for slo expression are discussed.

J Antimicrob Chemother, 2003 Mar, 51(3), 715 - 9
Spain14-5 international multiresistant Streptococcus pneumoniae clone resistant to fluoroquinolones and other families of antibiotics; Perez-Trallero E et al.; The Spain(14)-5 international multiresistant clone was initially described as resistant to penicillin, tetracycline, chloramphenicol and trimethoprim/sulfamethoxazole . In Gipuzkoa, Spain, Streptococcus pneumoniae isolated from 16 patients, and determined by PFGE and multilocus sequence typing to belong to the Spain(14)-5 clone, showed further resistance to fluoroquinolones (all strains had point mutations in the parC and gyrA genes) . In addition, most strains showed resistance to amoxicillin (MIC > or = 8 mg/L), cefotaxime (MIC > or = 2 mg/L), macrolides and lincosamides . Two strains were resistant to rifampicin (MIC 8 mg/L) . The multiresistance observed in these isolates converts the Spain(14)-5 clone into one of the most, if not the most, multiresistant of the international clones described.

J Antimicrob Chemother, 2003 Mar, 51(3), 707 - 10
A multidrug efflux phenotype mutant of Streptococcus pyogenes; Jones HE et al.; We describe a mutant of Streptococcus pyogenes NCTC 8198 with a multidrug efflux phenotype . A mutant selected with ethidium bromide showed a four-fold rise in MIC of norfloxacin, a 16-fold rise in MIC of ethidium bromide and an eight-fold rise in MIC of acriflavine when compared with the parent strain . The MICs were unaffected by the efflux pump inhibitors reserpine, rescinnamine and verapamil . The mutant's ethidium bromide MIC was reduced two-fold by norfloxacin . Ethidium bromide accumulation after 10 min was 58% lower in the mutant compared with the parent . This difference was not affected by carbonyl cyanide m-chlorophenylhydrazone.

J Antimicrob Chemother, 2003 Mar, 51(3), 691 - 6
Breakthrough pneumococcal bacteraemia in patients treated with clarithromycin or oral beta-lactams; Van Kerkhoven D et al.; The incidence of penicillin- and erythromycin-resistant strains of Streptococcus pneumoniae has increased considerably in Belgium . The medical charts of all patients with pneumococcal bacteraemia who were admitted to hospital over a period of 3 years (n = 136) were reviewed to identify treatment failure of outpatient antibiotic therapy . Twelve patients had received antibiotics for at least 48 h prior to admission . Four treatment failures received clarithromycin as pre-hospitalization therapy, and S . pneumoniae from all four patients were highly resistant to macrolides . Five patients failed on co-amoxiclav, whereas their S . pneumoniae were susceptible to penicillin and amoxicillin.This observation suggests that macrolide resistance is clinically relevant and leads to treatment failure, whereas suboptimal dosing may explain breakthrough pneumococcal bacteraemia in beta-lactam-treated patients.

J Antimicrob Chemother, 2003 Mar, 51(3), 639 - 49
Activity of daptomycin against susceptible and multidrug-resistant Gram-positive pathogens collected in the SECURE study (Europe) during 2000-2001; Critchley IA et al.; Antibiotic resistance was prevalent in Gram-positive pathogens collected from 40 sites in 15 European countries during 2000-2001 . Among Staphylococcus aureus, 27.3% of all isolates submitted were resistant to oxacillin and ranged from 0% of isolates from the Netherlands to 36.9% of isolates from Portugal . The overall prevalence of vancomycin-resistant Enterococcus faecium was 25.1%, with Italy submitting the largest percentage of resistant isolates (60.6%) . For Streptococcus pneumoniae, 9.4% of all isolates collected were resistant to penicillin with variation by country from 0% in the Netherlands to 20.7% in Portugal . Multidrug resistance (MDR), defined as concurrent resistance to three or more antimicrobials of different chemical classes, was observed in 24.6% of S . aureus, 19.6% of E . faecium and 3.6% of S . pneumoniae . The directed spectrum agents daptomycin, linezolid and quinupristin-dalfopristin were active in vitro against all isolates regardless of their resistance to other agents . Daptomycin and quinupristin-dalfopristin (MIC(90)s 0.5 mg/L) were equally active against oxacillin-resistant S . aureus compared with linezolid (MIC(90) 2 mg/L) . The activities of daptomycin, quinupristin-dalfopristin and linezolid were not affected by resistance to vancomycin in E . faecium (MIC(90)s of 4, 2 and 2 mg/L, respectively) . Daptomycin was more active against penicillin-resistant S . pneumoniae (MIC(90) 0.25 mg/L) than was quinupristin-dalfopristin (MIC(90) 0.5 mg/L) or linezolid (MIC(90) 2 mg/L) . Daptomycin was highly active against clinically important Gram-positive pathogens, including those that were multiply resistant to currently available agents . The results of this study provide a benchmark of the activity of daptomycin against contemporary European isolates and will serve as a baseline to monitor future changes in the susceptibility of these organisms to daptomycin.

Curr Opin Microbiol, 2003 Feb, 6(1), 50 - 5
IdeS and SpeB: immunoglobulin-degrading cysteine proteinases of Streptococcus pyogenes; von Pawel-Rammingen U et al.; The Gram-positive bacterium Streptococcus pyogenes is a major human pathogen causing substantial morbidity and mortality in society . S . pyogenes has evolved numerous molecular mechanisms to avoid the various actions of the human immune system and has established means to modulate both adaptive and innate immune responses . S . pyogenes produces and secretes proteolytic enzymes, which have an important impact on the ability of the bacteria to survive in the human host . Prominent among these are two immunoglobulin-degrading enzymes: the newly discovered streptococcal cysteine proteinase, IdeS, and the classical cysteine proteinase of S . pyogenes, SpeB.

Obstet Gynecol Surv, 2003 Mar, 58(3), 191 - 6
Group B streptococcus: prevention of early-onset neonatal sepsis; Platt JS et al.; Group B streptococcus (GBS) was recognized as a major pathogen of neonatal disease in the 1970s . With a case-fatality rate of 5% to 20%, prevention of GBS neonatal disease has been an ongoing concern . The Centers for Disease Control and Prevention (CDC), and American College of Obstetricians and Gynecologists (ACOG) published guidelines for preventive strategies in 1996 . These strategies, either a risk-based or a culture-based program, have been responsible for reduced incidence of GBS-newborn disease from 1.7 to 0.4 per 1,000 live births in the years 1993 to 1999 . However, there has been considerable variability in practice patterns . Reanalysis now shows that a culture-based prevention strategy provides greater reduction in early-onset neonatal disease than a risk-based protocol . The CDC replacement guidelines of August 2002 recommend culture-based GBS prevention; the risk-based strategy is no longer supported . Continued efforts to eradicate GBS-newborn disease require an understanding of the pathogen, colonization, and transmission, GBS sampling and detection methods, and maternal therapy . Until a reliable vaccination against GBS is developed, prevention of neonatal GBS disease will rely upon intrapartum treatment of maternal carriers . TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader will be able to define the pathogen, describe the methods of transmission and detection, and outline the current recommendations for maternal group B streptococcus therapy.

Pediatr Res, 2003 Apr, 53(4), 566 - 72 Epub 2003 Feb 20.
Neonatal skin in mice and humans expresses increased levels of antimicrobial peptides: innate immunity during development of the adaptive response; Dorschner RA et al.; The expression of antimicrobial peptides and proteins is an important innate immune defense mechanism that has recently been shown to be essential for cutaneous defense against invasive bacterial disease . Newborns have an immature cellular immune defense system that leads to increased susceptibility to infections . Here we show that skin from embryonic and newborn mice, as well as human newborn foreskin, express antimicrobial peptides of the cathelicidin and beta-defensin gene families . Immunohistochemistry and in situ hybridization demonstrated abundant cathelicidin protein and mRNA is present in normal skin during the perinatal period . Quantitative real-time PCR showed mouse cathelicidin expression (CRAMP) is 10- to 100-fold greater in the perinatal period than adult . Murine beta-defensins-1 and -4 and human beta-defensin-2 were also present in newborn skin . Combined, human cathelicidin (LL-37/hCAP/18) and beta-defensin-2 demonstrated synergistic antimicrobial activity and efficiently killed group B Streptococcus, an important neonatal pathogen . Antimicrobial peptides may therefore provide a compensatory innate defense mechanism during development of cellular immune response mechanisms in the newborn period.

Arch Microbiol, 2003 Mar, 179(3), 205 - 13 Epub 2003 Feb 04.
Molecular characterization of HPr and related enzymes, and regulation of HPr phosphorylation in the ruminal bacterium Streptococcus bovis; Asanuma N et al.; Molecular properties of HPr, enzyme I, and HPr kinase in Streptococcus bovis, and the regulation of HPr phosphorylation were examined . The genes encoding HPr (ptsH) and enzyme I (ptsI) were found to be cotranscribed . Two transcriptional start sites were detected in a region upstream of the HPr kinase gene (hprK) . HPr kinase had both HPr-phosphorylating and HPr-dephosphorylating activities . The importance of phosphorylation of Ser-46 in HPr was shown by using a mutant HPr in which Ser-46 was replaced by Ala . When S . bovis was grown in glucose-limited medium, the amount of seryl-phosphorylated HPr (HPr-{Ser-P}) decreased drastically as the growth rate decreased . In contrast, the amount of histidyl-phosphorylated HPr (HPr-{His-P}) increased gradually as the growth rate decreased . The amount of HPr kinase did not greatly change with the growth phase, whereas the intracellular P(i) concentration increased as the growth rate decreased . HPr-{Ser-P} decreased as the intracellular P(i) increased as a consequence of inhibition of HPr kinase activity by P(i) and simultaneous enhancement of HPr-{Ser-P} phosphatase activity by P(i) . Thus, it is conceivable that the ratio of HPr-{Ser-P} to HPr-{His-P} is regulated by the bifunctional activity of HPr kinase in response to intracellular P(i) concentration.

ANZ J Surg, 2003 Mar, 73(3), 136 - 9
Acute septic arthritis of the hip in children in northern Australia; Gandini D; BACKGROUND: The epidemiology, microbiology and clinical management of all children under 15 years of age presenting with acute septic arthritis of the hip to Royal Darwin Hospital from July 1994 to December 1999 were reviewed and the diagnostic value of various biological markers assessed . METHODS: Systematic review was undertaken of case notes of patients identified by searching the computerized hospital patient database and the admission records for the children's ward . RESULTS: Eleven cases were identified: 10 aboriginal and one caucasian . The mean temperature, white cell count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) at presentation were 39.2 degrees C, 15,500/mL, 65 mm/h and 144 mg/L, respectively . All had ESR and/or CRP >20 . Plain radiographs and ultrasonography were abnormal in 1/8 and 5/6 cases, respectively . Pathogens were isolated in nine cases: Staphylococcus aureus (n = 6), Streptococcus pyogenes (n = 2) and Streptococcus pneumoniae (n = 1) . Patients received intravenous antibiotics for 8.6 days (range: 3-15 days) and subsequent oral antibiotics for 22 days (range: 0-42 days) . The mean (range) time from hospital admission to arthrotomy; from hospital admission to antibiotic administration; and the overall hospital stay was 23 h (range: 3-48 h); 6 h (range: 0-48 h); and 41 days (range: 6-110 days), respectively . CONCLUSIONS: Elevation of temperature, white cell count, ESR and CRP were useful indicators of septic arthritis but initial diagnosis must be made on a clinical basis . Many patients had to be transferred from regional aboriginal communities and there was significant delay from onset of symptoms to arthrotomy.

J Periodontal Res, 2003 Apr, 38(2), 130 - 4
Effects of safrole on the defensive functions of human neutrophils; Hung SL et al.; The effects of safrole on the defensive functions of human neutrophils were examined . At the concentrations employed in this study, safrole did not significantly affect the viability of peripheral blood neutrophils as verified by their ability to exclude trypan blue dye . However, exposure of neutrophils to safrole inhibited their bactericidal activity against oral pathogens, including Actinobacillus actinomycetemcomitans and Streptococcus mutans, in a dose dependent manner . In addition, safrole inhibited the production of bactericidal superoxide anion by neutrophils as measured by cytochrome c reduction . In conclusion, the results demonstrated that safrole reduced the antibacterial activity and the superoxide anion production of neutrophils . Inhibition of the defensive functions of neutrophils may be one possible mechanism by which safrole compromises the oral health.

Acta Paediatr Taiwan, 2002 Sep-Oct, 43(5), 291 - 4
Necrotizing pneumonia caused by Streptococcus pneumoniae in a child with systemic lupus erythematosus; Chiu WJ et al.; Necrotizing pneumonia caused by Streptococcus pneumoniae is not an uncommon disease in children . Here we report a case of necrotizing pneumonia caused by Streptococcus pneumoniae in a 13-year-old girl . She was a case of systemic lupus erythematosus (SLE), and has long been treated with corticosteroids and azathioprine . She acquired pneumococcal necrotizing pneumonia later on . After appropriate antimicrobial therapy and surgical intervention, her condition stabilized and she recovered gradually . The present case suggests the need for a comprehensive diagnostic approach in patients with SLE who are undergoing immunosuppressive therapy, in order to screen for the possibility of infections if a new pulmonary pathologic process is present, even if the patient has no symptoms/signs indicating severe pulmonary infections.

Hua Xi Kou Qiang Yi Xue Za Zhi, 2002 Oct, 20(5), 374 - 6
{A study on screening effective immunization route of anticaries DNA vaccine pcDNA3-gtfB}; Yang J et al.; OBJECTIVE: Glucosyltransferase-B (GTF-B) of Streptococcus mutans has been implicated as a principal virulent factor in the development of dental caries . The objective was to use recombined plasmid pcDNA-gtfB expressing multiple antigen of glucosyltransferase-B as gene vaccine to immunize rats through different route, and to investigate the immunization effects of immunization routes . METHODS: A total of 18 Wistar rats were divided into 3 groups, including the quadriceps injection group, the intransal irrigation group and the submandibular gland-targeted injection group . The serum IgG and salivary IgA were assayed by using ELISA after pcDNA3-gtfB immunization . The serum IgG and salivary IgA in different groups were compared using statistical one-way ANOVA . RESULTS: Compared these 3 groups, the serum IgG in the quadriceps injection group was much higher than those of other two groups (P < 0.01), while the salivary IgA of the submandibular gland-targeted injection was much higher than those of other two groups (P < 0.01) . CONCLUSION: It is indicated pcDNA3-gtfB is good candidate for anticarious gene vaccine, and submandibular gland-targeted injection is an effective immunization route for stimulating salivary IgA.

Kansenshogaku Zasshi, 2002 Dec, 76(12), 1003 - 9
{The utility of the Pneumonia PORT prediction rule for evaluating the severity of community-acquired pneumonia in Japan . The relationship between disease severity and drug-resistant Streptococcus pneumoniae}; Nishiyama O et al.; To examine the utility of the Pneumonia PORT prediction rule for evaluating the severity of community-acquired pneumonia (CAP) in Japan, 127 consecutive patients with CAP admitted during one-year period were recruited and stratified by the rule . The relationship between CAP severity determined by the rule and drug-resistant Streptococcus pneumoniae was also investigated . The number of the patients classified into each class was 20 (15.7%) in class I, 32 (25.2%) in class II, 32 (25.2%) in class III, 31 (24.4%) in class IV, and 12 (9.4%) in class V, respectively . Risk class-specific mortality rate was 0% in class I and II, 3.1% in class III, 3.2% in class IV, and 41.7% in class V, respectively . Twenty-seven patients (21.3%) were diagnosed as pneumococcal pneumonia . In terms of penicillin-susceptibility of Streptococcus pneumoniae, 19 strains (70.4%) were penicillin-susceptible Streptococcus pneumoniae (PSSP) . Five (18.5%) were penicillin-intermediate Streptococcus pneumoniae (PISP), and 3 (11.1%) were penicillin-resistant Streptococcus pneumoniae (PRSP) . Highly resistant pneumococci with penicillin MIC > or = 4.0 micrograms/mL was not observed . For severity of drug-resistant pneumococcal pneumonia, 3 patients infected with PISP were classified as class IV, 2 with PISP were as class V, 2 with PRSP were as class IV, and 1 with PRSP was as class V . The patients with drug-resistant pneumococcal pneumonia were classified as high risk classes (class IV to V), however, the mortality rate was low (0%) . In conclusion, the Pneumonia PORT prediction rule is effective for evaluating the severity of CAP in Japan, especially in classifying the class V patients who are related to high mortality . The mortality rate of the patients with drug-resistant pneumococcal pneumonia was low.

Med Hypotheses, 2003 Feb, 60(2), 171 - 4
The next step in infectious disease: taming bacteria; Jones AH; Except for immunization programs our warfare with bacteria has always been a frontal assault with antibiotics . In this warfare we win battles, but with every new battle the enemy gets stronger . We need other options . Recent experience suggests two alternatives . First, public health measures designed to control the spread of infectious disease are associated with the selection of less virulent strains of microorganisms . Second, the same selection pressures obtained by public health measures outside the body are brought into play when we inhibit the adherence of bacteria within the body . Two recent studies using food sugars known to inhibit bacterial adherence show long-term benefits best explained by the previously observed decreases in bacterial virulence, following chronic exposure to the respective substances . Cranberry juice selects for less uropathogenic strains of Escherichia coli and xylitol for less caries producing Streptococcus mutans . The ability of these substances to reduce bacterial adherence in the human host has been known for some time, but poorly utilized . Their in vitro ability to decrease virulence has been reported but not clinically studied.

Expert Opin Investig Drugs, 2003 Mar, 12(3), 379 - 99
Novel antibacterial agents for the treatment of serious Gram-positive infections; Abbanat D et al.; With the continuing development of clinical drug resistance among bacteria and the advent of resistance to the recently released agents quinupristin-dalfopristin and linezolid, the need for new, effective agents to treat multi-drug-resistant Gram-positive infections remains important . This review focuses on agents presently in clinical development for the treatment of serious multidrug-resistant staphylococcal, enterococcal and pneumococcal infections, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and penicillin-resistant Streptococcus pneumoniae . Agents to be discussed that affect the prokaryotic cell wall include the antimethicillin-resistant S . aureus cephalosporins BAL9141 and RWJ-54428, the glycopeptides oritavancin and dalbavancin and the lipopeptide daptomycin . Topoisomerase inhibitors include the fluoroquinolones gemifloxacin, sitafloxacin and garenoxacin . Protein synthesis inhibitors are represented by the ketolides telithromycin and cethromycin, the oxazolidinones and the glycylcycline tigecycline . Although each of these compounds has demonstrated antibacterial activity against antibiotic-resistant pathogens, their final regulatory approval will depend on an acceptable clinical safety profile.

Lasers Surg Med, 2003, 32(3), 189 - 96
Efficacy of NaOCl/H2O2 irrigation and GaAlAs laser in decontamination of root canals in vitro; Kreisler M et al.; BACKGROUND AND OBJECTIVES: To investigate the bactericidal effect of an 809 nm semiconductor laser alone, and in combination with NaOCl/H(2)O(2) irrigation in root canals in vitro . STUDY DESIGN/MATERIALS AND METHODS: A total of 72 human single-rooted teeth extracted for periodontal reasons were included . The crowns were removed, the roots shortened to a length of 12 mm, and the canals enlarged up to an apical size of #50 file . The specimens were autoclaved and incubated with a suspension of Streptococcus sanguinis (ATCC 10556) . Laser irradiation was performed on a PC-controlled XY translation stage . A 200 micron optic fiber was used . Twelve specimens were irradiated at a power output of 1.5, 3.0, and 4.5 W in the cw-mode . The total irradiation time was 60 seconds per canal . Twelve specimens were rinsed with NaOCl and H(2)O(2) only, 12 were rinsed and laser treated, and 12 served as untreated controls . After laser treatment, the specimens were sonicated and the bacterial growth was examined by counting colony forming units on blood agar plates . Temperature changes at the outer root surface during irradiation were registered by means of thermocouples . Treated and control specimens were investigated by means of scanning electron microscopy . RESULTS: Mean bacterial reductions of 0.35 log steps at a power output of 1.5 W, 1.44 at 3.0 W, and 2.84 at 4.5 W were calculated . Bacterial reduction by the NaOCl/H(2)O(2) solution alone was 1.48 and comparable to that achieved by irradiation at 3.0 W . With a log kill 2.85, the combination of rinsing and laser irradiation at 3.0 W resulted in a further significant bacterial reduction as compared to rinsing alone (P = 0.004) . Irradiation did not result in excessive heat generation at the root surface . Carbonization of the root canal wall was observed in single teeth at 3.0 and 4.5 W and no controlled sealing of the dentinal tubules could be achieved in the root canal . CONCLUSIONS: The application of the diode laser might be an adjunct to conventional endodontic treatment when used in combination with a NaOCl/H(2)O(2) solution .

Circ J, 2003 Mar, 67(3), 275 - 6
Complete heart block resulting from quadricuspid aortic valve penicillin-resistant pneumococcal endocarditis: a case report; Watanabe Y et al.; A 62-year-old woman was referred to hospital to be treated for complete heart block with syncope . A quadricuspid aortic valve without vegetation and aortic valve regurgitation (AR) were observed by transesophageal echocardiography . Blood culture showed penicillin-resistant Streptococcus pneumoniae . The patient received a permanent pacemaker implantation (VDD type) and was given antibiotics . Although infection improved, heart failure was not improved because AR hemodynamic changes became worse . An aortic valve replacement was performed using a prosthesis on the 26th day of hospitalization . The patient recovered and was discharged.

Antimicrob Agents Chemother, 2003 Mar, 47(3), 1151 - 3
Lack of synergy of erythromycin combined with penicillin or cefotaxime against Streptococcus pneumoniae in vitro; Lin E et al.; We investigated a possible synergistic effect of a macrolide and beta-lactams against Streptococcus pneumoniae strains with different resistance profiles . Checkerboard and time-kill assays of erythromycin combined with penicillin or cefotaxime essentially showed indifference, suggesting that these antibiotics in combinations in vitro act substantially as individuals in their activity against S . pneumoniae.

Antimicrob Agents Chemother, 2003 Mar, 47(3), 1112 - 4
Erythromycin and clindamycin resistance and telithromycin susceptibility in Streptococcus agalactiae; Betriu C et al.; The rates of resistance to erythromycin and clindamycin among Streptococcus agalactiae strains isolated in our hospital increased from 4.2 and 0.8% in 1993 to 17.4 and 12.1%, respectively, in 2001 . Erythromycin resistance was mainly due to the presence of an Erm(B) methylase, while the M phenotype was detected in 3.8% of the strains . Telithromycin was very active against erythromycin-resistant strains, irrespective of their mechanisms of macrolide resistance.

Antimicrob Agents Chemother, 2003 Mar, 47(3), 1096 - 100
Mechanism of fluoroquinolone resistance is an important factor in determining the antimicrobial effect of gemifloxacin against Streptococcus pneumoniae in an in vitro pharmacokinetic model; MacGowan AP et al.; Antibacterial effect and emergence of resistance to gemifloxacin and levofloxacin were studied in an in vitro pharmacokinetic model of infection . A panel of Streptococcus pneumoniae strains with known mechanisms of resistance were used; two strains had no known resistance mechanism, two had efflux pumps, three had gyrA plus parC mutations, and one had only a parC mutation . Gemifloxacin MICs were in the range of 0.016 to 0.25 mg/liter, and levofloxacin MICs ranged from 1 to 16 mg/liter . Antimicrobial effect was measured by area under the bacterial-kill curve up to 72 h, and emergence of resistance was determined by population analysis profile before and during drug exposure . The area under the curve (AUC)/MIC ratios for gemifloxacin and levofloxacin were 35 to 544 and 3 to 48, respectively . As expected on the basis of these AUC/MIC ratio differences, antibacterial effect was much greater for gemifloxacin than levofloxacin . In the gemifloxacin simulations, mechanism of resistance as well as MIC determined the antibacterial effect, as indicated by gemifloxacin's greater effect against efflux strains compared to those with gyrA or parC mutations despite similar MICs . This was not true of levofloxacin . Emergence of resistance was not easily demonstrated with either agent, and mechanism of resistance did not have any impact on it.

Antimicrob Agents Chemother, 2003 Mar, 47(3), 1088 - 95
Activities of moxifloxacin against, and emergence of resistance in, Streptococcus pneumoniae and Pseudomonas aeruginosa in an in vitro pharmacokinetic model; MacGowan AP et al.; The pharmacodynamics of moxifloxacin against Streptococcus pneumoniae and Pseudomonas aeruginosa were investigated in a pharmacokinetic infection model . Three strains of S . pneumoniae, moxifloxacin, and two strains of P . aeruginosa were used . Antibacterial effect and emergence of resistance were measured for both species over a 72-h period using an initial inoculum of about 10(8) CFU/ml . At equivalent area under the curve (AUC)/MIC ratios, S . pneumoniae was cleared from the model while P . aeruginosa was not . For S . pneumoniae, the area under the bacterial kill curve up to 72 h could be related to AUC/MIC ratio using an inhibitory maximum effect (E(max)) model (concentration required for 50% E(max) {EC(50)}, 45 +/- 22; r(2), 0.97) . For P . aeruginosa even at the highest AUC/MIC ratio (427), bacterial clearance was insufficient for the EC(50) to be calculated . Emergence of resistance occurred with P . aeruginosa but not to any significant extent with S . pneumoniae . Emergence of resistance in P . aeruginosa as measured by population analysis profile (PAP-AUC) was dependent on drug exposure and time of exposure . In weighted least-squares regression analysis AUC/MIC ratio was predictive of PAP-AUC . When emergence of resistance was measured by the time for the colony counts on media containing antibiotic to increase by 2 logs, again AUC/MIC was the best predictor of emergence of resistance . However, for both experiments using S . pneumoniae and P . aeruginosa the correlation between all the pharmacodynamic parameters was high . These data indicate that for a given fluoroquinolone the magnitude of the AUC/MIC ratio for antibacterial effect is dependent on the bacterial species . Emergence of resistance is dependent on (i) species, (ii) duration of drug exposure, and (iii) drug exposure . A single AUC/MIC ratio magnitude is not adequate to predict antibacterial effect or emergence of resistance for all bacterial species.

Antimicrob Agents Chemother, 2003 Mar, 47(3), 923 - 31
In vitro activity of S-3578, a new broad-spectrum cephalosporin active against methicillin-resistant staphylococci; Fujimura T et al.; The in vitro antibacterial activity of S-3578, a new parenteral cephalosporin, against clinical isolates was evaluated . The MICs of the drug at which 90% of the isolates were inhibited were 4 micro g/ml for methicillin-resistant Staphylococcus aureus (MRSA) and 2 micro g/ml for methicillin-resistant Staphylococcus epidermidis, which were fourfold higher than and equal to those of vancomycin, respectively . The anti-MRSA activity of S-3578 was considered to be due to its high affinity for penicillin-binding protein 2a (50% inhibitory concentration, 4.5 micro g/ml) . In time-kill studies with 10 strains each of MRSA and methicillin-susceptible S . aureus, S-3578 caused more than a 4-log(10) decrease of viable cells on the average at twice the MIC after 24 h of exposure, indicating that it had potent bactericidal activity . Furthermore, in population analysis of MRSA strains with heterogeneous or homogeneous resistance to imipenem, no colonies emerged from about 10(9) cells on agar plates containing twice the MIC of S-3578, suggesting the low frequency of emergence of S-3578-resistant strains from MRSA . S-3578 was also highly active against penicillin-resistant Streptococcus pneumoniae (PRSP), with a MIC(90) of 1 micro g/ml, which was comparable to that of ceftriaxone . S-3578 also had antibacterial activity against a variety of gram-negative bacteria including Pseudomonas aeruginosa, though its activity was not superior to that of cefepime . In conclusion, S-3578 exhibited a broad antibacterial spectrum and, particularly, had excellent activity against gram-positive bacteria including methicillin-resistant staphylococci and PRSP . Thus, S-3578 was considered to be worthy of further evaluation.

Antimicrob Agents Chemother, 2003 Mar, 47(3), 863 - 8
Low-level resistance to rifampin in Streptococcus pneumoniae; Meier PS et al.; Rifampin is recommended for combination therapy of meningitis due to beta-lactam-resistant Streptococcus pneumoniae . High-level rifampin resistance (MIC, > or =4 mg/liter) has been mapped to point mutations in clusters I and III of rpoB of the pneumococcus . The molecular basis of low-level resistance (MICs, > or =0.5 and <4 mg/liter) was analyzed . Spontaneous mutants of clinical pneumococcal isolates were selected on Columbia sheep blood agar plates containing rifampin at 0.5, 4, 10, or 50 mg/liter . Low-level resistance could be assigned to mutations in cluster II (I(545)N, I(545)L) . Sensitive (MIC, <0.048 mg/liter) wild-type strains acquired low-level resistance at a rate approximately 10 times higher than that at which they acquired high-level resistance (average mutation frequencies, 2.4 x 10(-7) for low-level resistance versus 2.9 x 10(-8) for high-level resistance {P < 0.0001}) . In second-step experiments, the frequencies of mutations from low- to high-level resistance were over 10 times higher than the frequencies of mutations from susceptibility to high-level resistance (average mutation frequencies, 7.2 x 10(-7) versus 5.0 x 10(-8) {P < 0.001}) . Mutants with low-level resistance were stable upon passage . Sequencing of a clinical isolate with low-level resistance (MIC, 0.5 mg/liter) revealed a Q(150)R mutation upstream of cluster I . The frequencies of mutations to high-level resistance for this strain were even higher than the rates observed for the in vitro mutants . Therefore, a resistance-mediating mutation located outside clusters I, II, and III has been described for the first time in the pneumococcus . In vitro low-level rifampin resistance in S . pneumoniae could be mapped to cluster II of rpoB . Mutants of pneumococcus with low-level resistance may be selected in vivo during therapy in tissue compartments with low antibiotic concentrations and play a role in the development of resistance.

Emerg Infect Dis, 2003 Feb, 9(2), 211 - 6
Using hospital antibiogram data to assess regional pneumococcal resistance to antibiotics; Stein CR et al.; Antimicrobial resistance to penicillin and macrolides in Streptococcus pneumoniae has increased in the United States over the past decade . Considerable geographic variation in susceptibility necessitates regional resistance tracking . Traditional active surveillance is labor intensive and costly . We collected antibiogram reports from North Carolina hospitals and assessed pneumococcal susceptibility to multiple agents from 1996 through 2000 . Susceptibility in North Carolina was consistently lower than the national average . Aggregating antibiogram data is a feasible and timely method of monitoring regional susceptibility patterns and may also prove beneficial in measuring the effects of interventions to decrease antimicrobial resistance.

Ethiop Med J, 2002 Jul, 40(3), 241 - 9
Investigation on the antibacterial properties of garlic (Allium sativum) on pneumonia causing bacteria; Dikasso D et al.; The antibacterial activity of the crude aqueous extract of garlic was investigated against some pneumonia causing bacteria by an agar dilution technique . The results revealed that Streptococcus pneumoniae standard test organism was completely inhibited by 7.8 mg/ml of media and the clinical isolate of Klebsiella pneumoniae was completely inhibited by 24.38 mg/ml of media, indicating that Streptococcus pneumoniae is the most sensitive and Klebsiella pneumoniae the least . Garlic could be used as an effective antibacterial agent for these pathogenic microorganisms.

Zhejiang Da Xue Xue Bao Yi Xue Ban, 2002 Aug, 31(6), 464 - 466
{Influence of different DNA extractions on the identification of streptococcus sanguis group by arbitrary primed polymerase chain reaction}; Zhang WD et al.; OBJECTIVE: To assess the influence of different DNA extractions on the identification of streptococcus sanguis group (SSG) species by arbitrary primed polymerase chain reaction (AP-PCR) . METHODS: AP-PCR was used to distinguish SSG species by designing 25bp arbitrary primer 5'AAG AGA GGA GCT AGC TCT TCT TGG A 3', and the genomic DNA was extracted by 3 methods . RESULTS: There were great differences in the main band of DNA polymorphism among SSG species . The similar band could be got from the different DNA extractions in the same species . CONCLUSION: Different DNA extractions have no influence on the identification of SSG.

Immunol Lett, 2003 Mar 3, 86(1), 85 - 91
Naturally occurring immune response against bacteria commonly involved in upper respiratory tract infections: analysis of the antigen-specific salivary IgA levels; Rossi GA et al.; Lyophilized bacterial lysates, which actively stimulate the immune response, are widely used as vaccines or 'biological response modifiers' in subjects with recurrent bacterial respiratory infections . Since vaccines are indicated in the absence or in the presence of a weak constitutive immune response activity, a better knowledge on the 'naturally' occurring antibacterial immune response at the oropharingeal level should be helpful . A study was, therefore, designed to quantify the presence of salivary IgA directed against surface antigens bacteria frequently involved in the pathogenesis of upper respiratory tract infections: Klebsiella pneumoniae (KP), Staphylococcus aureus (SA), Streptococcus pyogenes (SPy), Morraxella catarrhalis (MC), Haemophylus influenzae (HI), and Streptococcus pnumoniae (SPn) . In 34 volunteers (21 adults and 13 children), salivary fluid was collected and the presence of microorganism-specific IgA antibodies evaluated by a novel enzyme immuno-assay . In the whole population only 29 and 24% of subjects had IgA directed, respectively, to KP and SA, while the immune-response against other microbes was detectable in a small population ranging from 12 to 15% of all subjects studied . We found higher proportions of individuals with strain specific salivary IgA in the adult than in the pediatric population for all the microorganism evaluated . In addition, in children, the only strain inducing a significant production of specific IgA at oropharingeal level was KP . Interestingly, only ten out of 21 adults and two out 13 children have at least one significantly high antibody titer against one of the bacteria evaluated . Nevertheless, when a group of healthy donors was treated with a polyvalent mechanical bacterial lysate (Ismigen t.), the large majority developed a specific immune-response in the salivary fluid . These results are thus consistent with the good features of the novel enzyme-immunoassay and with a poor frequency of naturally induced specific anti-microbe antibodies in children and in adults despite the presence on recurrent respiratory infections in their clinical history.

Nippon Geka Gakkai Zasshi, 2002 Dec, 103(12), 851 - 5
{Prosthetic valve endocarditis: complication following cardiac surgery}; Motomura N et al.; Prosthetic valve endocarditis (PVE) is a rare but serious complication following valve replacement surgery . Early-phase PVE, which occurs within 60 days of valve replacement, may be associated with nosocomial or intraoperative infection . The primary organism of this type is the Staphylococcus group . Late-phase PVE, which usually occurs more than one year after valve replacement, may be caused by a mechanism similar to that of native valve endocarditis . The primary causative organism of this type would thus be similar to that of native valve endocarditis, which is the Streptococcus group . To treat PVE effectively, it is extremely important to identify the primary causative organism . If uncontrollable cardiac failure or infection occurs, a second valve replacement is absolutely indicated . A cryopreserved aortic valve allograft, if available, is the first choice for PVE . Features such as cell viability, less compliance mismatch, and postantibiotic process could be reasons for the anti-infective characteristics of cryopreserved allografts . Currently, allograft valves are not widely available in Japan; therefore, conventional prosthetic valves are usually used . The use of antibiotic-soaked prosthetic valves or stentless xenograft valves has also been attempted . A genetic or tissue engineering approach could open a new era to overcome this lethal complication.

Hua Xi Yi Ke Da Xue Xue Bao, 2002 Jan, 33(1), 62 - 4, 107
{The influence of two implant materials on the growth of three subgingival predominant bacteria}; Gao N et al.; OBJECTIVE: Commercially pure titanium and titanium alloy as dental implants have show impressive clinical results . Despite the high success rates, some implants do fail . Compared to those studies on osseointegration of implants, the information pertaining to their failure is little . Further studies on the relationship between implant material and micro-organism are needed . The purpose of this investigation is to study the effect of two commonly used implant materials Titanium (TA2) and Ti-6AI-4V alloy (TC4) on the growth behaviour of three subgingival predominant bacteria Streptococcus sanguis (S . s), Porphyromanus gingivalis (P . g), Fusobacterium nucleatum (F . n) and their mixture . METHODS: Under anaerobic condition, bacterial suspensions of S.s, P.g, F.n and their mixture were incubated together with the two implant materials respectively, setting the same bacterial suspensions as controls . After 2, 7 and 14 days, the bacterial growth amount was assayed by means of clone forming unit (CFU) method . The pH value of the bacterial suspension was determined by pH-Meter . RESULTS: The results showed that there was no difference in amount of bacterial growth or pH value between TA2 group and TC4 group (P > 0.05) . There was also no statistically significant change as to the proportion of individual bacteria in bacterial mixture or the pH value of culture suspension . CONCLUSION: Under the condition of this investigation, the two studies implant materials have no examined influences on the growth of the subgingival bacteria and the pH value of their culture environment.

Rev Neurol, 2003 Feb, 36 Suppl 1, S95 - 107
{Autoimmune neuropsychiatric disorders associated to infection by streptococcus in the paediatric age: PANDAS}; Betancourt YM et al.; INTRODUCTION: The acronym PANDAS (Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus) describes the neuropsychiatric disorders resulting from an autoimmune response to an infection by streptococcus in children . AIMS: The aim of this study was to clinically analyse 38 patients under the age of 16 with tics, Tourette syndrome (TS) or obsessive compulsive disorder (OCD) and their possible association to an infection caused by group A beta-haemolytic streptococcus (GABHS) . METHOD: We reviewed the medical records at the Instituto Neurologico in Valencia (Venezuela) over a 12 year period (1988-2000) . All the patients met the inclusion criteria set out by the National Institute of Mental Health in Bethesda (1997) and the DSM-IV . RESULTS: Onset of the symptoms was higher in the group of schoolchildren (n=24), followed by the group of preschool children (n=8) and adolescents (n=6) . Males were predominant (n=33) (86.8%) . 17 patients presented chronic tics (44.7%), 13 had transitory tics (34.2%) and there were eight cases of TS (21.1%) . The most frequently related comorbid disorders were: difficulties in learning (n=30) (78.9%), ADHD (n=27) (71.1%), OCD 14 (36.8%), sleep disorders (n=14) (36.8%), behavioural disorders (n=12) (31.6%), language disorders (n=11) (28.9%), psychomotor disorders (n=10) (26.3%) and nocturnal enuresis (n=7) (18.4%) . Electroencephalogram patterns were abnormal in 72.4% (n=12), and the disorganised pattern was the most frequently observed (n=12) (41.4%), followed by a slow diffuse pattern (n= 7) (24.1%) and the left centro-parieto-temporal focal paroxysmal specific pattern (n=7) (24.1%) . Less frequently we found unspecific generalised paroxysmal patterns, in four cases (13.8%), and asymmetrical patterns (n=1) (3.4%) . The association with an infection by streptococcus was shown in two cases, which amounted to 5.2% of the sample . CONCLUSIONS: The obtained are similar to those reported in the literature . Only 5.2% of the cases were linked to a prior streptococcus infection.

J Infect Dis, 2003 Feb 15, 187(4), 604 - 12 Epub 2003 Jan 28.
Intrahost sequence variation in the streptococcal inhibitor of complement gene in patients with human pharyngitis; Matsumoto M et al.; Selection of new variants of the streptococcal inhibitor of complement protein has been implicated in the perpetuation of epidemics caused by serotype M1 strains of group A Streptococcus (GAS) . The frequency at which new streptococcal inhibitor of complement (Sic) variants arise in an infected individual is not known . To study this issue, the sic gene was sequenced in 100 isolates cultured from throat swabs of each of 20 patients with acute pharyngitis caused by serotype M1 GAS . Five patients were infected with GAS populations expressing 2 Sic variants characterized by deletion of a region of the protein . In contrast, no intrahost variation was detected in the number of a pentanucleotide repeat (CAAAA) that controls production of a bacterial cell-surface collagen-like protein by slipped-strand mispairing . Sic variation occurs at a sufficient frequency in vivo to result in mixed infections on the mucosal surface of human hosts, potentially contributing to pathogen survival.

J Infect Dis, 2003 Feb 15, 187(4), 597 - 603 Epub 2003 Feb 07.
Survival of Streptococcus pyogenes within host phagocytic cells: a pathogenic mechanism for persistence and systemic invasion; Medina E et al.; Streptococcus pyogenes is generally an extracellular pathogen that can survive and persist within the host by circumventing the host defense mechanisms . To achieve this, S . pyogenes has developed a number of strategies to circumvent the host immune system (e.g., virulence factors directed to prevent phagocytosis) . By use of a murine model of skin infection, it was shown that survival within host phagocytic cells constitutes an additional strategy used by S . pyogenes to evade the host defenses and disseminate . Viable microorganisms were isolated from mouse phagocytic cells after in vitro or during in vivo infection . The capacity of intracellularly located bacteria to establish infection was demonstrated by the efficiency of gentamicin-treated neutrophils isolated from infected mice to transfer infection when injected intravenously into naive mice . The ability of S . pyogenes to exploit the inflammatory response of the host by surviving inside phagocytic cells may constitute an additional virulence mechanism of this pathogen.

J Infect Dis, 2003 Feb 15, 187(4), 589 - 96 Epub 2003 Jan 29.
Nationwide surveillance of nasopharyngeal Streptococcus pneumoniae isolates from children with respiratory infection, Switzerland, 1998-1999; Muhlemann K et al.; The surveillance of pneumococcal antibiotic resistance and serotype distribution is hampered by the relatively low numbers of invasive pneumococcal infections . In Switzerland, a nationwide sentinel surveillance network was used to assess antibiotic resistance and serotype distribution among 1179 pneumococcal isolates cultured from 2769 nasopharyngeal swabs obtained from outpatients with acute otitis media or pneumonia during 1998 and 1999 . The proportion of penicillin-susceptible pneumococcal isolates overall (87%) and among infants <2 years old (81%) was comparable to that of invasive isolates (90% and 81%, respectively) . The high number of nasopharyngeal isolates allowed for the detection of a rapid increase in the number of penicillin-nonsusceptible pneumococcal (PNSP) strains in the West region of Switzerland, partly because of an epidemic caused by the 19F clone of Streptococcus pneumoniae . Clustering of risk factors for the carriage of PNSP isolates further explained the geographic variation in resistance rates . The nationwide sentinel surveillance of nasopharyngeal pneumococcus proved to be valuable for the monitoring of antibiotic resistance, risk factors for carriage of PNSP isolates, and serotype distribution and for the detection of the emergence of a new epidemic clone.

J Dermatol, 2003 Jan, 30(1), 69 - 71
A case of baboon syndrome associated with group a streptococcal infection; Ichimiya M et al.; We described a 21-year-old Japanese patient with sore throat, fever, and diffuse erythema on the neck, trunk, and limbs . Erythema markedly appeared on the neck, axillary, antecubital, and popliteal fossae . However, other skin signs of scarlet fever such as red strawberry tongue and linear petechial eruption did not appear . Before his visit to our clinic, he had been diagnosed as pharyngitis and treated with cefaclor 750 mg daily for six days . However, the symptoms did not improve . Oral prednisolone of 20 mg daily rapidly improved all the symptoms . Pharyngeal culture grew Streptococcus pyogenes that was sensitive to cefaclor . Laboratory findings showed elevated serum levels of antibody against streptolysin O . Together with the distribution of erythema, culture of Streptococcal pyogenes, and elevated anti-streptolysin O titer, the diagnosis of baboon syndrome associated with streptococcal infection was made . This seems to be the first report of baboon syndrome due to streptococcal infection.

Arch Dis Child, 2003 Mar, 88(3), 211 - 4
Pneumococcal nasopharyngeal carriage in children following heptavalent pneumococcal conjugate vaccination in infancy; Lakshman R et al.; AIMS: To ascertain whether the reduction in nasopharyngeal carriage of vaccine serotypes induced by pneumococcal conjugate vaccine (PnCV) administered to infants persists beyond the age of 2 years . METHODS: Non-randomised, unblinded controlled study of 2-5 year old children who had received three doses of heptavalent PnCV (7VPnCV) in infancy and 23-valent pneumococcal polysaccharide vaccine at 13 months, and unimmunised controls . Nasopharyngeal swabs were taken in summer (150 vaccinated subjects, 126 controls) and winter (143 vaccinated subjects, 188 controls) . The swabs were cultured and serotyped for Streptococcus pneumoniae . RESULTS: Carriage rates (vaccinated subjects: 24.7% and 43.4%; controls: 27.0% and 41.0%, in summer and winter respectively) and carriage of vaccine serotypes (subjects: 10.0% and 30.0%; controls: 13.5% and 31.5%, in summer and winter respectively) were similar in the two groups . CONCLUSIONS: Effects of vaccination in infancy on rates of nasal carriage of pneumococcus and serotype replacement in children living in a largely unvaccinated population are no longer evident by 2-5 years of age.

Am J Respir Crit Care Med, 2003 Mar 1, 167(5), 764 - 70
Impaired pulmonary inflammatory responses are a prominent feature of streptococcal pneumonia in mice with experimental emphysema; Inoue S et al.; Little is known about why patients with chronic obstructive pulmonary disease are susceptible to bacterial infections . Using an animal model of pulmonary emphysema, we investigated the inflammatory responses to bacterial infection . After intratracheal infection with Streptococcus pneumoniae (10(3)-10(7) cfu/mouse), the control mice did not die . However, the mice with emphysema died in a dose-dependent manner . Bronchoalveolar lavage fluid, examined 24 hours after infection showed that the numbers of total cells and neutrophils, in addition to murine tumor necrosis factor-alpha and macrophage inflammatory protein-2 concentrations, were significantly less in the mice with emphysema compared with the control mice . Histopathologic findings revealed that the alveoli were filled with inflammatory cells and exudate in the control mice but not in the mice with emphysema . Seventy-two hours after infection, serum cytokine levels were significantly higher in the mice with emphysema, and significant numbers of S . pneumoniae were detected in both the whole lung tissues and the blood of mice with emphysema . These findings suggest that the inflammatory response in mice with emphysema was impaired at the site of bacterial infection despite the bacteremia, which accelerated severe systemic inflammatory responses . Accordingly, intra-alveolar but not systemic immune responses to bacterial infection were impaired in the presence of experimental emphysema.

Protein Expr Purif, 2003 Feb, 27(2), 346 - 56
Cloning, over-expression, purification, and characterisation of N-acetylneuraminate synthase from Streptococcus agalactiae; Suryanti V et al.; N-acetylneuraminate synthase (NeuAc-synthase; E.C . 4.1.3.19) is one of the two enzymes responsible for sialic acid (N-acetylneuraminic acid) synthesis in bacteria . Potential genes encoding NeuAc synthase in Streptococcus agalactiae and Bacillus subtilis were identified from a BLAST search of the EMBL/GenBank/DDBJ database using the E . coli neuB gene sequence as a probe and the genes cloned and expressed at high level in Escherichia coli . The neuB gene of S . agalactiae was shown to encode an active NeuAc synthase, whereas the spsE gene product from B . subtilis did not have this activity . Expression of the native S . agalactiae neuB gene product enzyme in E . coli resulted in a product that was prone to proteolysis during purification so the protein was tagged with a hexa-histidine tag at its N-terminus and the enzyme was rapidly purified to homogeneity by ammonium sulphate fractionation and Ni-chelating affinity chromatography in two steps . Measurement of the subunit molecular mass by electrospray ionisation mass spectrometry (M(r) = 38, 987 +/- 3) and of the native molecular mass by gel filtration chromatography (M(r) = 78,000) clearly demonstrated that the enzyme is dimeric . The effects of EDTA, temperature, and pH on the activity of the S . agalactiae NeuAc synthase were examined . Enzyme activity was maximal at pH 7 and was dependent on the presence of metal ions such as Mg(2+), Mn(2+) or Co(2+) . The purified enzyme was inhibited by the reagent phenylglyoxal and the substrates N-acetyl mannosamine or phosphoenol pyruvate afforded protection against this inhibition, suggesting that one or more arginine residues are involved in substrate recognition and binding . The ease of expression and the properties of the enzyme should now permit a thorough study of the specificity of the enzyme and provide the prerequisites for attempts to alter this specificity by directed evolution for the production of novel sialic acid analogues .

Ann Otol Rhinol Laryngol, 2003 Feb, 112(2), 191 - 4
Natural history of sigmoid sinus thrombosis; Agarwal A et al.; To demonstrate the evolution of sigmoid sinus thrombosis, we performed a prospective observational study on a 6-year-old girl who presented with mastoiditis, epidural abscess, and occipital osteomyelitis from multiple drug-resistant Streptococcus pneumoniae . She underwent mastoidectomy and partial occipital craniectomy . This procedure produced a window in the occipital bone that allowed serial ultrasonography of the sigmoid sinus during medical treatment . Computed tomography was performed, followed by weekly Doppler ultrasonography used to monitor resolution of sigmoid sinus thrombosis . The natural history of a treated episode of sigmoid sinus thrombosis was illustrated . Venous occlusion resolved over a 4- to 6-week period without surgical drainage or venous anticoagulants . Collateral flow, reversal of normal venous flow, and ultimate return to normal venous transport characterized the period of resolution . We conclude that an occluded sigmoid sinus from mastoiditis can naturally recanalize . Aberrant venous flow can be demonstrated during the period of resolution . This case supports a conservative approach to management of the occluded sinus and suggests that 4 to 6 weeks of antibiotic therapy after removal of perisinus infection is sufficient for cure.

Infect Immun, 2003 Mar, 71(3), 1462 - 9
Amino acid sequence requirements in the hinge of human immunoglobulin A1 (IgA1) for cleavage by streptococcal IgA1 proteases; Batten MR et al.; The amino acid sequence requirements in the hinge of human immunoglobulin A1 (IgA1) for cleavage by IgA1 proteases of different species of Streptococcus were investigated . Recombinant IgA1 antibodies were generated with point mutations at proline 227 and threonine 228, the residues lying on either side of the peptide bond at which all streptococcal IgA1 proteases cleave wild-type human IgA1 . The amino acid substitutions produced no major effect upon the structure of the mutant IgA1 antibodies or their functional ability to bind to Fcalpha receptors . However, the substitutions had a substantial effect upon sensitivity to cleavage with some streptococcal IgA1 proteases, with, in some cases, a single point mutation rendering the antibody resistant to a particular IgA1 protease . This effect was least marked with the IgA1 protease from Streptococcus pneumoniae, which showed no absolute requirement for either proline or threonine at residues 227 to 228 . By contrast, the IgA1 proteases of Streptococcus oralis, Streptococcus sanguis, and Streptococcus mitis had an absolute requirement for proline at 227 but not for threonine at 228, which could be replaced by valine . There was evidence in S . mitis that proteases from different strains may have different amino acid requirements for cleavage . Remarkably, some streptococcal proteases appeared able to cleave the hinge at a distant alternative site if substitution prevented efficient cleavage of the original site . Hence, this study has identified key residues required for the recognition of the IgA1 hinge as a substrate by streptococcal IgA1 proteases, and it marks a preliminary step towards development of specific enzyme inhibitors.

Infect Immun, 2003 Mar, 71(3), 1179 - 84
Immunogenicity and protective immunity induced by synthetic peptides associated with putative immunodominant regions of Streptococcus mutans glucan-binding protein B; Smith DJ et al.; Glucan-binding protein B (GbpB) from Streptococcus mutans has been shown to induce protective immunity to dental caries in experimental models . Having recently sequenced the gbpB gene, our objective in this study was to identify immunogenic regions within the GbpB sequence for use in subunit vaccines . Potential regions of immunogenicity were sought by use of a matrix-based algorithm (EpiMatrix) to estimate the binding characteristics of peptides derived from the GbpB sequence by using a database of known major histocompatibility complex class II binding alleles . Screening the entire sequence revealed several peptides with estimated high binding probabilities . Two N-terminal 20-mer peptides (SYI and QGQ) subtending two of these regions were synthesized . A preliminary experiment, in which these peptides were synthesized in the multiple antigenic peptide format and were used to subcutaneously immunize Sprague-Dawley rats twice at a 21-day interval, revealed that the SYI peptide induced a higher percentage of responses to the inciting peptide as well as to intact GbpB, as measured by enzyme-linked immunosorbent assay . The effect of immunization with the SYI peptide construct on the cariogenicity of S . mutans was then investigated by immunizing weanling Sprague-Dawley rats twice at a 9-day interval with SYI or with phosphate-buffered saline . All rats were then orally infected with S . mutans strain SJ . After a 78-day infection period, the SYI-immunized groups had significant reductions in dental caries on both smooth and occlusal surfaces compared with the sham-immunized group . Thus, these experiments indicated that at least one linear sequence, derived from the N-terminal third of GbpB, was sufficiently immunogenic to induce a protective immune response in this experimental rat model for dental caries.

Infect Immun, 2003 Mar, 71(3), 1042 - 55
Identification and characterization of a Streptococcus pyogenes operon involved in binding of hemoproteins and acquisition of iron; Bates CS et al.; The hemolytic Streptococcus pyogenes can use a variety of heme compounds as an iron source . In this study, we investigate hemoprotein utilization by S . pyogenes . We demonstrate that surface proteins contribute to the binding of hemoproteins to S . pyogenes . We identify an ABC transporter from the iron complex family named sia for streptococcal iron acquisition, which consists of a lipoprotein (siaA), membrane permease (siaB), and ATPase (siaC) . The sia transporter is part of a highly conserved, iron regulated, 10-gene operon . SiaA, which was localized to the cell membrane, could specifically bind hemoglobin . The operon's first gene encodes a novel bacterial protein that bound hemoglobin, myoglobin, heme-albumin, and hemoglobin-haptoglobin (but not apo-haptoglobin) and therefore was named Shr, for streptococcal hemoprotein receptor . PhoZ fusion and Western blot analysis showed that Shr has a leader peptide and is found in both membrane-bound and soluble forms . An M1 SF370 strain with a polar mutation in shr was more resistant to streptonigrin and hydrogen peroxide, suggesting decreased iron uptake . The addition of hemoglobin to the culture medium increased cell resistance to hydrogen peroxide in SF370 but not in the mutant, implying the sia operon may be involved in hemoglobin-dependent resistance to oxidative stress . The shr mutant demonstrated reduced hemoglobin binding, though cell growth in iron-depleted medium supplemented with hemoglobin, whole blood, or ferric citrate was not affected, suggesting additional systems are involved in hemoglobin utilization . SiaA and Shr are the first hemoprotein receptors identified in S . pyogenes; their possible role in iron capture is discussed.

Infect Immun, 2003 Mar, 71(3), 1033 - 41
Regions of PspA/EF3296 best able to elicit protection against Streptococcus pneumoniae in a murine infection model; Roche H et al.; Pneumococcal surface protein A (PspA) can elicit protection against Streptococcus pneumoniae in mouse infection models . PspA is classified by serology and amino acid sequence into two major families that are divided by sequence into five clades . The most variable portion of the molecule is the alpha-helical domain, which comprises the N-terminal half of PspA . Prior studies of a family 1 PspA protein observed that protective antibodies are reactive with epitopes in the alpha-helical domain and that most cross-protective epitopes mapped to the 108 most C-terminal amino acids of the alpha-helical region . In these studies, we have used six overlapping recombinant fragments of family 2, clade 3 PspA/EF3296 to map the protection-eliciting regions of its alpha-helical domain . The three fragments, which included the 104 most C-terminal amino acids of the alpha-helical domain (314 to 418), could each elicit protection against EF3296 . A fragment comprising amino acids 75 to 305 failed to elicit significant protection . A fragment containing amino acids 1 to 115 elicited protection against EF3296 in BALB/c mice but not in CBA/N mice . All three fragments containing amino acids 314 to 418 were able to elicit cross-protection against pneumococci expressing PspA proteins of clades 2, 3, 4, and 5 . Cross-protection elicited by these three fragments was easier to demonstrate in CBA/N mice than in BALB/c mice . The 1-to-115 fragment, however, elicited some cross-protection against clades 2 and 4 in BALB/c mice but not in CBA/N mice . These studies provide support for the importance of the C-terminal 104 and N-terminal 115 amino acids of the alpha-helical region of PspA in the elicitation of cross-protection.

J Immunol, 2003 Mar 1, 170(5), 2274 - 8
Cutting edge: mast cell antimicrobial activity is mediated by expression of cathelicidin antimicrobial peptide; Di Nardo A et al.; Cathelicidins (caths) are peptides that are expressed at high levels in neutrophils and some epithelia and can act as natural antibiotics by directly killing a wide range of microorganisms . We hypothesized that caths are expressed in mast cells (MCs), because these cells have been previously associated with inherent antimicrobial activity . Cultured murine MCs contained abundant amounts of cathelin-related antimicrobial peptide (AMP), the murine cath, and this expression was inducible by LPS or lipoteichoic acid . Human skin MCs also expressed cath as detected by immunohistochemical analysis for the human cath LL-37 . The functional significance of this expression was shown by comparing MCs cultured from normal mice to MCs from littermates deficient in the cathelin-related AMP gene (Cnlp(-)) . MCs derived from Cnlp(-/-) animals had a 50% reduction in their ability to kill group A STREPTOCOCCUS: These MCs expressed equivalent amounts of mRNA for murine beta-defensin-4, a beta-defensin AMP . Thus, different antimicrobials can be identified in MCs, and the presence of cath is necessary for efficient bacterial killing . These observations suggest that the presence of cath is vital to the ability of mammalian MCs to participate in antimicrobial defense.

J Biol Chem, 2003 May 2, 278(18), 15587 - 94 Epub 2003 Feb 19.
Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Staphylococcus aureus activates immune cells via Toll-like receptor (TLR)-2, lipopolysaccharide-binding protein (LBP), and CD14, whereas TLR-4 and MD-2 are not involved; Schroder NW et al.; Lipoteichoic acid (LTA) derived from Streptococcus pneumoniae, purified employing a chloroform/methanol protocol, and from Staphylococcus aureus, prepared by the recently described butanol extraction procedure, was investigated regarding its interaction with lipopolysaccharide (LPS)-binding protein (LBP), CD14, Toll-like receptors (TLRs)-2 and -4, and MD-2 . LTA from both organisms induced cytokine synthesis in human mononuclear phagocytes . Activation was LBP- and CD14-dependent, and formation of complexes of LTA with LBP and soluble CD14 as well as catalytic transfer of LTA to CD14 by LBP was verified by PhastGel(TM) native gel electrophoresis . Human embryonic kidney (HEK) 293/CD14 cells and Chinese hamster ovary (CHO) cells were responsive to LTA only after transfection with TLR-2 . Additional transfection with MD-2 did not affect stimulation of these cells by LTA . Our data suggest that innate immune recognition of LTA via LBP, CD14, and TLR-2 represents an important mechanism in the pathogenesis of systemic complications in the course of infectious diseases brought about by the clinically most important Gram-positive pathogens . However, the involvement of TLR-4 and MD-2 in this process was ruled out.

FEMS Microbiol Lett, 2003 Feb 14, 219(1), 143 - 50
Cloning and expression of hyaluronate lyase genes of Streptococcus intermedius and Streptococcus constellatus subsp . constellatus(1); Takao A; Hyaluronate lyase (HAase) genes of Streptococcus intermedius and Streptococcus constellatus subsp . constellatus were isolated . In S . constellatus subsp . constellatus, the deduced amino acid sequence of HAase was most similar to that of S . intermedius (68%), whereas the enzyme of S . intermedius was most similar to that of S . pneumoniae (72%) . Upstream of the HAase gene on the opposite strands, an open reading frame of a putative glutathione peroxidase started in S . intermedius, and this arrangement was similar to that in S . pneumoniae but unlike that in S . constellatus subsp . constellatus . Cell lysates of Escherichia coli carrying each streptococcal gene showed HAase activity, demonstrating that each cloned gene actually coded for HAase.

FEMS Microbiol Lett, 2003 Feb 14, 219(1), 9 - 15
Regulation of protein H expression in M1 serotype isolates of Streptococcus pyogenes; Smith TC et al.; Protein H is an immunoglobulin-binding protein expressed by certain M1 serotypes of Streptococcus pyogenes . In a recent study of invasive group A isolates, it was found that none of the 16 M1 serotype isolates analyzed expressed protein H on their surface despite the presence of the protein H gene (sph) in approximately one-third of the isolates . Selection of stable protein H-expressing variants could be achieved by infection of prtH(+) non-expressing strains into a mouse skin and recovering bacteria from the spleen . This effect was independent of the transcription regulator Mga, since a similar effect was noted in an mga(-) mutant . Thus, host passage of S . pyogenes can lead to stable high level expression of Protein H.

Hua Xi Kou Qiang Yi Xue Za Zhi, 2002 Feb, 20(1), 62 - 5
{Construction of the pyruvate oxidase gene deficiency variant strain of Streptococcus oralis}; Pang R et al.; OBJECTIVE: The purpose of this study is to construct a pyruvate oxidase gene deficiency variant strain of Streptococcus oralis (S . oralis) . METHODS: The sopox gene, which was got using polymerase chain reaction (PCR), and the 130-basepair segment of which was cut down with endonuclease BamHI, and transferred into S . oralis (ATCC10557) by using electrotransformation . The authors obtained a variant strain of S . oralis, and then the catalase activity of the first culture and 3-4 subcultures was examined . RESULTS: The authors obtained a pyruvate oxidase gene deficiency variant strain of S . orlis . The catalase activity examination showed that the ability of producing H2 O2 of the variant strain of S . orlis declined, whose catalase activity was between those of the positive control (ATCC10557) and the negative control (Escherichia coli, JM109) . But the produced H2 O2 quantity of their subcultures was less than that of the negative control . CONCLUSION: The construction of the pyruvate oxidase gene deficiency variant strain of Streptococcus oralis is successful.

Hua Xi Kou Qiang Yi Xue Za Zhi, 2002 Feb, 20(1), 14 - 7
{A study of tarnish induced by Streptococcus sobrinus serotype g on Co-Cr, Ni-Cr and casting titanium alloys}; Song Y et al.; OBJECTIVE: The objective of this study was to investigate the tarnish induced by Streptococcus sobrinus serotype g on Co-Cr, Ni-Cr and casting titanium alloys . METHODS: Co-Cr, Ni-Co and casting titanium alloys were respectively machined into a size of 10 mm x 10 mm x 1 mm in tablets, and totally 90 specimens with 30 of each were prepared for the test . The 30 specimens of each alloy were randomly and equally divided into three subgroups, including the blank control group, the media control group and the inoculated media group . Under the aerobic condition, the surfaces of the sucrose agar media were inoculated with Streptococcus sobrinus serotype g . The labeled sterile specimens were placed on the surface of the media for 10 weeks . The specimens were changed to a new sucrose media with bacteria each week . The specimens were removed after 10 weeks of incubation, immersed in 0.05% glutaraldehyde solution to eliminate AaY4, rinsed with distilled water . After 2 weeks, the specimens were removed and observed visually or examined by MINOLTA CR-100 color apparatus . RESULTS: Compared with the blank control, the control media without bacteria did not influence the alloy specimens (P > 0.05) . Streptococcus sobrinus serotype g caused tarnish on specimens . There was significant difference between the control media group and the blank control group with inoculated media group on all the specimens (P < 0.05) . CONCLUSION: Streptococcus sobrinus serotype g affects the color of Co-Cr, Ni-Cr and casting titanium alloys, but the color does not change from yellow-green range to red-yellow range.

Protein Sci, 2003 Mar, 12(3), 567 - 76
Mutations in the B1 domain of protein G that delay the onset of amyloid fibril formation in vitro; Ramirez-Alvarado M et al.; We previously reported that under certain experimental conditions, many variants of the B1 domain of IgG-binding protein G from Streptococcus form fibrils reproducibly . The variant I6T53 was the focus of the present study because the lag phase in the kinetics of fibril formation by this variant is significantly longer than that of other variants . This lag phase is distinguished by changes in both intrinsic fluorescence intensity and in light scattering of the protein . NMR diffusion measurements suggest that the soluble protein during the lag phase is monomeric . The kinetic profiles of fibril formation are found to depend on experimental conditions . The first kinetic phase diminishes almost completely when the reaction is seeded with preformed amyloid fibrils.

J Bacteriol, 2003 Mar, 185(5), 1650 - 8
Functional characterization of penicillin-binding protein 1b from Streptococcus pneumoniae; Di Guilmi AM et al.; The widespread use of antibiotics has encouraged the development of drug resistance in pathogenic bacteria . In order to overcome this problem, the modification of existing antibiotics and/or the identification of targets for the design of new antibiotics is currently being undertaken . Bifunctional penicillin-binding proteins (PBPs) are membrane-associated molecules whose transpeptidase (TP) activity is irreversibly inhibited by beta-lactam antibiotics and whose glycosyltransferase (GT) activity represents a potential target in the antibacterial fight . In this work, we describe the expression and the biochemical characterization of the soluble extracellular region of Streptococcus pneumoniae PBP1b (PBP1b*) . The acylation efficiency for benzylpenicillin and cefotaxime was characterized by stopped-flow fluorometry and a 40-kDa stable TP domain was generated after limited proteolysis . In order to analyze the GT activity of PBP1b*, we developed an electrophoretic assay which monitors the fluorescence signal from PBP1b*-bound dansylated lipid II . This binding was inhibited by the antibiotic moenomycin and was specific for the GT domain, since no signal was observed in the presence of the purified functional TP domain . Binding studies performed with truncated forms of PBP1b* demonstrated that the first conserved motif of the GT domain is not required for the recognition of lipid II, whereas the second motif is necessary for such interaction.

FEMS Immunol Med Microbiol, 2003 Jan 21, 35(1), 49 - 58
Pro-inflammatory cytokine and chemokine release by human brain microvascular endothelial cells stimulated by Streptococcus suis serotype 2; Vadeboncoeur N et al.; Streptococcus suis serotype 2 is a world-wide agent of diseases among pigs including meningitis, septicemia and arthritis . This microorganism is also recognized as an important zoonotic agent . The pathogenesis of the meningitis caused by S . suis is poorly understood . We have previously shown that S . suis is able to adhere to human brain microvascular endothelial cells (BMEC), but not to human umbilical vein endothelial cells (HUVEC) . The objective of this work was to study the ability of S . suis serotype 2 to induce the release of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1); IL-6 and the chemokines IL-8 and monocyte chemotactic protein-1 (MCP-1) by human BMEC and HUVEC, using a sandwich enzyme-linked immunosorbent assay . S . suis was able to stimulate the production of IL-6, IL-8 and MCP-1 by BMEC but not HUVEC, in a time- and concentration-dependent manner . Bacterial cell wall components were largely responsible for such stimulation . The human and pig origin of strains does not seem to affect the intensity of the response; indeed, a very heterogeneous pattern of cytokine and chemokine production was observed for the different strains tested in this study . In situ production of cytokines and chemokines by BMEC may be the result of specific adhesion of S . suis to this cell type, with several consequences such as increased recruitment of leukocytes and an increase in the blood-brain barrier permeability.

Oral Microbiol Immunol, 2003 Feb, 18(1), 50 - 3
Comparison of different techniques of quantitative PCR for determination of Streptococcus mutans counts in saliva samples; Rupf S et al.; Saliva samples from 16 children with current caries activity were investigated for Streptococcus mutans using three different PCR techniques, and the results were compared with those of selective cultivation on mitis salivarius agar with bacitracin (MSB) (I, II: LightCycler - competitive PCR end-point analysis; III: LightCycler - kinetic real-time analysis; IV, V: block cycler - competitive PCR end-point analysis; VI: cultivation on MSB agar) . In groups I, III, IV and VI the saliva samples were analyzed directly . A DNA preparation before PCR with added competitors was carried out in groups II and V to exclude the influence of PCR inhibitors . The coefficients of correlation ranged from 0.97 to 0.98 among the competitive PCR methods, 0.8 to 0.85 for competitive vs . real-time PCR and 0.5 to 0.65 for PCR vs . cultivation methods . Competitive PCR on the real-time instrument was found to be more rapid than, comparably sensitive to, but less reproducible than competitive PCR on a block cycler.

Clin Microbiol Infect, 2003 Feb, 9(2), 140 - 3
Evidence for efflux pumps, other than PmrA, associated with fluoroquinolone resistance in Streptococcus pneumoniae; Brenwald NP et al.; Fluoroquinolone resistance in pneumococci is known to be associated with the efflux pump, PmrA . However, there may be other efflux systems that also cause drug resistance . Two types of mutants were studied . The efflux phenotype from mutants selected by sub-MIC levofloxacin or gemifloxacin was transformed into R6 . These transformants did not show increased pmrA transcripts in Northern blots; insertional inactivation of pmrA in the transformants did not abolish the efflux phenotype . A second set of efflux phenotype mutants was selected in R6:cat by ethidium bromide but not by norfloxacin; accumulation of ethidium bromide in the one among these mutants studied was reduced in comparison to its parent . This evidence suggests that systems other than PmrA can contribute to efflux-mediated resistance in pneumococci.

Arch Intern Med, 2003 Feb 24, 163(4), 467 - 72
Clinical and epidemiologic features of group a streptococcal pneumonia in Ontario, Canada; Muller MP et al.; BACKGROUND: Since the 1960s, group A streptococcus (GAS) has accounted for less than 1% of cases of community-acquired pneumonia . During the past 2 decades there has been a resurgence of invasive GAS infection, but no large study of GAS pneumonia has been performed . METHODS: To determine the clinical and epidemiologic features of GAS pneumonia, we conducted prospective, population-based surveillance of all invasive GAS infection in residents of Ontario from January 1, 1992, through December 31, 1999 . RESULTS: Of 2079 cases of invasive GAS infection, 222 (11%) represented GAS pneumonia . The incidence of GAS pneumonia ranged from 0.16 per 100 000 in 1992 to 0.35 per 100 000 in 1999 . Most cases were community acquired (81%) . Forty-four percent of nursing home-acquired cases occurred during outbreaks . The case fatality rate was 38% for GAS pneumonia, compared with 12% for the entire cohort with invasive GAS infection and 26% for patients with necrotizing fasciitis . The presence of streptococcal toxic shock syndrome (odds ratio, 19; 95% confidence interval, 8.4-42; P =.001) and increasing age (odds ratio per decade, 1.45; 95% confidence interval, 1.2-1.7; P<.001) were associated with fatal outcome . Time to death was rapid, with a median of 2 days despite antimicrobial therapy and supportive measures . CONCLUSIONS: Group A streptococcal pneumonia is a common form of invasive GAS disease but remains an uncommon cause of community-acquired pneumonia . Progression is rapid despite appropriate therapy . The incidence is similar to, and the case fatality rate higher than, that of necrotizing fasciitis.

Scand J Infect Dis, 2002, 34(12), 921 - 2
Ophthalmia neonatorum caused by group B Streptococcus; Poschl JM et al.; A full-term infant was born with a swollen left conjunctival sac . Ophthalmia neonatorum developed within 5 d after birth . Examination of the purulent discharge showed Group B Streptococcus . The CRP level was found to be elevated and parenteral and topical therapy was started . Ophthalmia neonatorum resolved after 7 d of treatment.

Scand J Infect Dis, 2002, 34(12), 887 - 92
Management of patients with community-acquired pneumonia treated in hospital in Sweden; Hedlund J et al.; To investigate the management of patients with community-acquired pneumonia (CAP) treated in hospital in Sweden, a multicentre retrospective cohort study was performed with medical record review of 982 patients (mean age 63 y) at 17 departments of infectious diseases at hospitals in Sweden . Information on antimicrobial therapy, demographic characteristics, comorbid conditions, physical examination findings, and laboratory and microbiological test results were recorded . Outcome measures were in-hospital mortality and length of hospital stay (LOS) . Cultures were obtained from blood in 80% and from sputum in 22% of the patients . A microbiological aetiology was determined for 23% of the patients, with Streptococcus pneumoniae as the dominating agent (9%) . The initial antibiotic treatment was mostly given intravenously (78%) . Penicillin (50%) or a cephalosporin (30%) was the most common choice . Both of these drugs were usually given as a single agent . The overall mortality was 3.5% and the mean LOS was 6.4 d . Thus, the outcome was favourable despite the empirical antibiotic treatment having a narrow spectrum compared with the broader approach recommended in most recent guidelines on the management of CAP . These findings suggest that a majority of patients who are hospitalized with moderately severe pneumonia can be treated initially with penicillin alone.

Rev Esp Enferm Dig, 2002 Sep, 94(9), 533 - 6
Bacteriology of anal fistulae; de San Ildefonso Pereira A et al.; OBJECTIVE: To evaluate by bacteriological analysis the possible relationship between the chronicity of perianal fistulae and the presence of probable permanent infection of the fistulae . MATERIAL AND METHODS: The study included 27 patients, 21 men and 6 women who had undergone surgery for chronic perianal fistulae type II (according to the Parks classification) . A total of 27 samples of their fistulous tracts were sent to the microbiology department for the identification of germs . All samples were taken from the theatre and delivered to the laboratory in the same manner . They were then processed under de same conditions in terms of dilutions, inoculation and culture mediums used for the identification of germs in the tracks of the fistulae . RESULTS: A total of 45 were isolated from 21 different species of microorganisms . Most samples (78.26%) had polymicrobic growth . The predominant species were: Escherichia coli (45.45%), Bacteroides fragilis (16.66%), Staphylococcus aureus (12.12%) and Streptococcus viridans (12.12%) . No Mycobacteria were found in any specimen . CONCLUSIONS: Anal fistulae can be colonized by poli- or mononormal intestinal or skin microbacterial flora or a combination of both . This report suggests that neither the type or the number of germs its related to the chronicity of cryptoglandular anal fistulae.

Rev Esp Quimioter, 2002 Dec, 15(4), 313 - 24
{Quinolones and Streptococcus pneumoniae . Mechanisms of action and resistance}; Talens-Visconti R et al.; Streptococcus pneumoniae is considered the most frequent bacterial cause of community-acquired pneumonia, and is involved in a significant number of cases of acute exacerbations of chronic bronchitis, acute otitis, sinusitis, meningitis and other infectious diseases . Fluoroquinolones have been extensively investigated in recent years in the search for new agents that has been prompted by the emergence of resistance in this microorganism . Furthermore, the study of resistance from a molecular biology standpoint has helped in elucidating almost all the biochemical mechanisms of resistance and the routes of dissemination of genetic information between bacteria . This short review is focused on the mechanism of action of quinolones and on the mechanisms responsible for resistance of S . pneumoniae to them, given their clinical and epidemiological relevance . S . pneumoniae is a case apart because bactericidal activity against this microorganism can be produced through gyrase, topoisomerase IV or both, depending on the quinolone structure, which shows that structure has an influence on the success of treatment . Knowledge of the resistance prototype is therefore important so that the appropriate antibiotic therapy can be recommended when indicated.

Pediatr Infect Dis J, 2003 Feb, 22(2), e1 - 11
Report from a WHO Working Group: standard method for detecting upper respiratory carriage of Streptococcus pneumoniae; O'Brien KL et al.; BACKGROUND: Numerous studies evaluating the efficacy of conjugate pneumococcal vaccines are being conducted or planned throughout the world . Some of these studies are evaluating the effect of vaccine on nasopharyngeal (NP) carriage . METHODS: The World Health Organization established a Working Group comprised of representatives from these trials and other NP colonization experts to establish core, standardized methods for the study of pneumococcal NP colonization that could be used in these trials . The intent was to reduce or eliminate variability in key methods which themselves could contribute to variability of observed pneumococcal NP colonization . In this way variability of vaccine effects between trials on NP colonization could more easily be analyzed for population or vaccine differences without the confounding effect caused by differences in study methodology . RESULTS: This paper presents the evidence base supporting the need for standardized NP colonization study methods, the methods themselves (Core Consensus Methods), including collection techniques, culture media, equipment, serotyping, storage of specimens and transport of isolates agreed on by the Working Group as well as a discussion of research priorities . CONCLUSIONS: The Core Consensus Methods provide a common methodology to conduct pneumococcal NP colonization studies with minimum interstudy method variability . The intention is to allow more meaningful comparisons of study results from conjugate pneumococcal vaccine trials.

Pediatr Infect Dis J, 2003 Feb, 22(2), 133 - 40
Report from a WHO working group: standard method for detecting upper respiratory carriage of Streptococcus pneumoniae; O'Brien KL et al.; BACKGROUND: Numerous studies evaluating the efficacy of conjugate pneumococcal vaccines are being conducted or planned throughout the world . Some of these studies are evaluating the effect of vaccine on nasopharyngeal (NP) carriage . METHODS: The World Health Organization established a Working Group composed of representatives from these trials and other NP colonization experts to establish core, standardized methods for the study of pneumococcal NP colonization that could be used in these trials . The intent was to reduce or eliminate variability in key methods which themselves could contribute to variability of observed pneumococcal NP colonization . In this way variability of vaccine effects between trials on NP colonization could more easily be analyzed for population or vaccine differences without the confounding effect caused by differences in study methodology . RESULTS: This paper presents the evidence base supporting the need for standardized NP colonization study methods, the methods themselves (Core Consensus Methods found in the electronic version of this article at and on the WHO website at including collection techniques, culture media, equipment, serotyping, storage of specimens and transport of isolates agreed on by the Working Group as well as a discussion of research priorities . CONCLUSIONS: The Core Consensus Methods provide a common methodology to conduct pneumococcal NP colonization studies with minimum interstudy method variability . The intention is to allow more meaningful comparisons of study results from conjugate pneumococcal vaccine trials.

Can J Surg, 2003 Feb, 46(1), 9 - 14
Necrotizing fasciitis secondary to chickenpox infection in children; Clark P et al.; BACKGROUND: Necrotizing fasciitis is an uncommon but serious complication of chickenpox infection in young children . Because many of these infections affect the musculoskeletal tissues, orthopedic surgeons are often the first caregivers to be involved in diagnosis and treatment . Our objective was to review the diagnostic features of necrotizing fasciitis and analyze treatment methods to control and eradicate the musculoskeletal infection . DESIGN: A review . SETTING: The Children's Hospital of Eastern Ontario, Ottawa, a major Canadian pediatric trauma and referral centre . PATIENTS: Five children who presented with necrotizing fasciitis secondary to chickenpox infection . INTERVENTION: Surgical debridement of the involved area of necrotizing fasciitis and intravenous antibiotic treatment with clindamycin and penicillin . MAIN OUTCOME MEASURES: Complications outcome . RESULTS: The average age of the 5 children at presentation was 3.8 years (range from 2.9-5.8 yr) . The necrotizing fasciitis involved the lower extremity in 5 children, the upper extremity in 3, and the abdomen, chest, neck and back in 1 child each . One child presented with involvement of all 4 extremities . In 4 children, culture specimens grew group A beta-hemolytic Streptococcus . They all survived and all limbs were salvaged, although secondary closure and skin grafting were required . At an average follow-up of 1 year, each child had fully recovered with no loss of muscle function . CONCLUSIONS: Necrotizing fasciitis should be suspected in any child with a history of varicella infection and an increasing complaint of pain and swelling in an extremity or other body area associated with increasing fever, erythema, lethargy and irritability . Emergent surgical debridement and intensive antibiotic therapy are essential to prevent muscle necrosis, major limb dysfunction and death.

FEMS Microbiol Lett, 2003 Jan 21, 218(1), 79 - 84
A polymerase chain reaction (PCR) assay specific for Streptococcus suis based on the gene encoding the glutamate dehydrogenase; Okwumabua O et al.; Polymerase chain reaction (PCR) primers that flank a 688-bp segment within the glutamate dehydrogenase gene (gdh) of Streptococcus suis type 2 could amplify efficiently the DNA of all 306 (100%) clinical S . suis isolates tested (pigs, n=305; human, n=1) encompassing all serotypes obtained from diverse organs, and geographic origins . When DNA from other bacteria were used as templates for amplification, no product was detected indicating specificity of the primers . Multiplex PCR was developed using the gdh gene primer pair and primers that targeted the gene encoding S . suis capsular biosynthesis (cps) . This strategy enabled the detection of strains belonging to serotypes 1/2, 1, 2, 7, and 9, respectively . Using the multiplex-PCR technique, 12 out of 14 (86%) isolates that were previously identified as non-typable S . suis (based on biochemical reactions and serology) gave positive PCR results of which four were positive for serotype 7, three for serotype 2, and five for S . suis strains that belong to other serotypes . Retest results of all 14 isolates by several veterinary laboratories were identical with PCR and confirmed that the two non-PCR reactive isolates belonged to strains of other streptococcal species . These results indicated that PCR improved species determination and can thus be used as a reliable species-specific molecular diagnostic reagent for the accurate identification of S . suis isolates and a serotype-specific method for the detection of strains of serotypes 1/2, 1, 2, 7, and 9, respectively . The PCR method therefore has potential clinical and epidemiological applications.

J Chemother, 2002 Dec, 14(6), 584 - 90
In vivo pharmacodynamic evaluation of clarithromycin in comparison to erythromycin; Novelli A et al.; The efficacy of various dosing regimens of clarithromycin and erythromycin against recently isolated Streptococcus pneumoniae strains was determined in vivo using two animal infection models (mouse peritonitis and thigh infection) . For the thigh infection model, mice received a total dose of 4 mg/Kg of either clarithromycin or erythromycin, as a single total dose or divided into 2, 4 or 8 doses/24h . After 24h of therapy S . pneumoniae organisms were killed at 2.06 to 4.03 log10 CFU/thigh by clarithromycin and the one- or two-dose regimens were significantly more effective than the four- or eight-dose regimens . Organism killing following 24h of therapy with erythromycin ranged from 1.13 to 2.31 log10 CFU/thigh, with the one- or two-dose regimens significantly less effective than the four- or eight-dose regimens . In the mouse survival study, the same dose of either clarithromycin or erythromycin was given as a single total dose or divided into two or four doses with dosing intervals of 4 and 2-times the t1/2 respectively . The results obtained in this model show that there is a significant difference in survival when clarithromycin is administered less frequently (4% deaths for the one-dose regimen in comparison to 40% deaths with the four-dose regimen, P < 0.01, Chi-square test) . With erythromycin there was a trend for increased survival with the multiple-dose regimen, with significantly higher survival when concentrations exceeding the MIC were maintained for a longer time period . These results indicate that the time during which serum concentrations exceeding the MIC value of the pathogen is an important parameter for efficacy for erythromycin . On the contrary, results with both animal models demonstrate that bacterial killing and survival are significantly higher among clarithromycin-treated mice when the antibiotic is administered less frequently and the highest Cmax/MIC ratio is achieved.

Neurosci Lett, 2003 Mar 6, 338(3), 201 - 4
Matrix metalloproteinase-9 deficiency impairs host defense mechanisms against Streptococcus pneumoniae in a mouse model of bacterial meningitis; Bottcher T et al.; Matrix metalloproteinase-9 (MMP-9) appears to contribute to blood-brain barrier damage and neuronal injury in bacterial meningitis . To further explore the function of MMP-9 in meningeal inflammation, we injected 10(4) colony forming units (CFU) of a Streptoccocus pneumoniae type 3 strain into the right forebrain of MMP-9 deficient mice (MMP-9(-/-), n=16) and wild-type controls (129 x B6, n=15) . The clinical course of the disease, leukocyte recruitment into the subarachnoid space and bacterial titers in the brain did not differ . Yet, clearance of the bacteria from blood (log CFU/ml 4.7 {3.8/5.4} vs . 3.6 {3.0/4.0}; P=0.005) and spleen homogenates (log CFU/ml 5.3 {4.8/5.5} vs . 4.0 {2.8/4.7}; P=0.01) was reduced in MMP-9 deficient mice . A reduced systemic bacterial clearance of MMP-9(-/-) mice was confirmed in experimental S . pneumoniae peritonitis/sepsis . This implies a compromised systemic, but not intracerebral host response against S . pneumoniae in MMP-9 deficiency.

Pediatr Rehabil, 2002 Jul-Sep, 5(3), 171 - 6
Microbiology and management of post-surgical wounds infection in children; Brook I; The recent increased recovery of anaerobic bacteria from children has led to greater appreciation of their role in paediatric infections at all body sites, including post-surgical wounds (PSW) . In studies that employed adequate method for recovery of aerobic and anaerobic bacteria polymicrobial, aerobic and anaerobes were isolated from over half of the patients with PSW . The wounds studied were those that developed following these surgical procedures: head and neck surgery for malignancies, post-thoracotomy, spinal fusion and gastrostomy tube insertion . Staphylococcus aureus and aerobic gram-negative bacilli were found at all sites . However, a correlation was generally found between the site of the wounds and microbial flora recovered from the wound . Organisms that resided in the mucous membranes close to the surgical site predominated in the wound next to these areas . Enteric Gram-negative rods, Group D enterococcus and Bacteroides fragilis group predominated in wounds relating to the gut flora, while Streptococcus spp., pigmented Prevotella and Porphyromonas spp . and Fusobacterium spp . were most frequently recovered in wounds proximal to the oral area . Management of PSW should include administration of antimicrobials effective against the polymicrobial bacterial flora adjacent to the anatomic site of the wound.

Yao Xue Xue Bao, 2001 Aug, 36(8), 581 - 4
{Synthesis and antibacterial activity of 3-hydroxy-6-O-methylerythromycin-9-O-substituted oxime derivatives}; Chen SX et al.; AIM: To study the antibacterial activity against erythromycin-resistant organisms of 3-hydroxy-6-O-methylerythromycin-9-O-substituted oxime derivatives, a new route of synthesis with 6 steps was designed . METHODS: The starting material, erythromycin A (1), was reacted with NH2OH.HCI to give 2, which reacted with BzBr to give 3 . Selective methylation of C-6 hydroxy group using iodomethane afforded 4, which was hydrolyzed with loss of the 3-cladinosyl to give 5 . Compound 5 was reduced by H2 to provide 6, which was treated with substituted benzyl chlorides to provide 7 and 8 . RESULTS: Four unreported compounds (5-8) were synthesized . The antibacterial activity of the new compounds were tested in vitro against both erythromycin-susceptible and erythromycin-resistant organisms . The compounds 5 (MIC = 1 microgram.mL-1) and 6 (MIC = 1 microgram.mL-1) showed significant activity against Staphylococcus epidermidis 26,069 compared with erythromycin (MIC = 4 micrograms.mL-1) . Compounds 5 (MIC = 16, 4 micrograms.mL-1), 7 (MIC = 32, 64 micrograms.mL-1) and 8 (MIC = 64, 32 micrograms.mL-1) showed better activity against Streptococcus pneumoniae 64 and Staphylococcus aureus 9525 than erythromycin (MIC > 128, 128 micrograms.mL-1) . CONCLUSION: 3-hydroxy-6-O-methylerythromycin-9-O-substituted oxime derivatives have stronger antibacterial activity against some erythromycin-resistant organisms than erythromycin A.

Reproduction, 2003 Feb, 125(2), 295 - 9
Effects of Gram-positive bacterial pathogens in ewes: peptidoglycan as a potential mediator of interruption of early pregnancy; Stewart AB et al.; Bacterial cell walls contain peptidoglycan (PTG), which, among other actions, induces fever . The present experiment evaluated the effects of PTG treatment on early pregnancy and blood plasma concentrations of reproductive hormones . Ewes were injected i.v . with saline or 15, 30 or 60 microg kg(-1) sonicated PTG (Streptococcus pyogenes) on day 5 after mating . Each dose of PTG induced fever . Pregnancy rate at day 25 was not related to incidence of fever but tended to differ among treatments (control, 100%; low, 100%; medium, 67%; high, 60%; P < 0.08) . Combined pregnancy rate in ewes from control and low dose groups (100%) was greater than that in ewes from medium and high dose groups (64%, P < 0.01) . Ewes with high 13,14-dihydro-15-keto-prostaglandin F(2alpha) (PGFM) concentrations had lower pregnancy rates (6 of 10) than those with low concentrations of PGFM (11 of 11; P < 0.05) . Mean cortisol concentrations were higher in treated (2.8 +/- 0.28 microg dl(-1)) than in control (1.1 +/- 0.03 microg dl(-1)) ewes (P < 0.01); the pattern of secretion was biphasic and increased in all treated ewes (P < 0.01) . Neither means nor profiles of oestradiol differed with treatment . Mean concentrations and the pattern of concentrations of progesterone were reduced in all treated ewes, as indicated by the time by treatment and linear interaction with treatment (1.2 +/- 0.1 versus 1.6 +/- 0.1 ng ml(-1), P < 0.01) . Patterns of LH pulses did not differ from 0 to 4 h or 24 to 28 h after treatment; mean plasma LH concentration was lower in ewes treated with 0, 15 or 30 microg PTG kg(-1) than with 60 microg PTG kg(-1) (P < 0.01) . Pregnancy status was not related to plasma concentrations or patterns of LH, oestradiol, progesterone or cortisol . Inflammatory mediators, such as PGF(2alpha), may act directly on the embryo or uterus in ewes treated with PTG.

MMWR Morb Mortal Wkly Rep, 2003 Jan 31, 52(4), 64 - 6
Pneumococcal conjunctivitis at an elementary school--Maine, September 20-December 6, 2002; Psoas abscess diagnosed at a Northern university hospital; Department of Infectious Diseases, Ullevaal University Hospital, Oslo, Norway . anne.maagaard@ullevaal.no

Abscess of the psoas muscle is an infrequent diagnosis at hospitals in Northern countries . We report on 16 patients who had this diagnosis during the period 1991-2001 . Eight patients were immigrants who had previously been healthy and most of them had experienced symptoms for approximately 1 y . MRI or CT scans revealed spondylodiscitis in 6 of these patients and Mycobacterium tuberculosis was identified as the causative agent . With the exception of 1 patient who was exclusively treated with antituberculous agents, all 8 immigrant patients were successfully treated with antituberculous agents in addition to percutaneous drainage . The other 8 patients were Norwegians, 4 of whom had underlying conditions such as diabetes mellitus or drug abuse . The causative microorganisms were Staphylococcus aureus or Streptococcus spp., with the exception of M . tuberculosis in 1 case . The Norwegian patients had a more acute history of symptoms than the immigrant patients and 2 of them were in a septic condition on admittance . Two of the Norwegians died of serious infection; 5 were successfully treated with percutaneous drainage in addition to antibiotics and 1 was treated exclusively with antibiotic agents . The clinical history and microorganism associated with psoas abscess seemed to depend on whether or not the patient was an immigrant . Owing to increasing immigration, diagnosis of psoas abscess should be taken into account in Northern countries.

Scand J Infect Dis, 2002, 34(11), 847 - 8
Primary group A streptococcal peritonitis in a previously healthy child; Gillespie RS et al.; Primary peritonitis in a child without underlying medical conditions is rare outside the neonatal period . A girl with no past medical history presented with acute abdominal pain . Laparotomy revealed primary peritonitis due to group A Streptococcus (serotype emm89) . She was treated with antibiotics and immune globulin, and recovered fully.

Proc Natl Acad Sci U S A, 2003 Feb 18, 100(4), 1996 - 2001 Epub 2003 Feb 06.
Genome-wide protective response used by group A Streptococcus to evade destruction by human polymorphonuclear leukocytes; Voyich JM et al.; Group A Streptococcus (GAS) evades polymorphonuclear leukocyte (PMN) phagocytosis and killing to cause human disease, including pharyngitis and necrotizing fasciitis (flesh-eating syndrome) . We show that GAS genes differentially regulated during phagocytic interaction with human PMNs comprise a global pathogen-protective response to innate immunity . GAS prophage genes and genes involved in virulence, oxidative stress, cell wall biosynthesis, and gene regulation were up-regulated during PMN phagocytosis . Genes encoding novel secreted proteins were up-regulated, and the proteins were produced during human GAS infections . We discovered an essential role for the Ihk-Irr two-component regulatory system in evading PMN-mediated killing and promoting host-cell lysis, processes that would facilitate GAS pathogenesis . Importantly, the irr gene was highly expressed during human GAS pharyngitis . We conclude that a complex pathogen genetic program circumvents human innate immunity to promote disease . The gene regulatory program revealed by our studies identifies previously undescribed potential vaccine antigens and targets for therapeutic interventions designed to control GAS infections.

J Clin Microbiol, 2003 Feb, 41(2), 613 - 8
Analysis of a viridans group strain reveals a case of bacteremia due to lancefield group G alpha-hemolytic Streptococcus dysgalactiae subsp equisimilis in a patient with pyomyositis and reactive arthritis; Woo PC et al.; Streptococcus dysgalactiae is classified by a combination of phenotypic and genotypic characteristics into Lancefield group C alpha-hemolytic Streptococcus dysgalactiae subsp . dysgalactiae and Lancefield group C, group G, and group L beta-hemolytic Streptococcus dysgalactiae subsp . equisimilis . In this study, we report the isolation of a catalase-negative, alpha-hemolytic, optochin- and bacitracin-resistant viridans group strain, which does not grow in 10 or 40% bile, on MacConkey agar or bile esculin agar, or in 6% NaCl, from the blood culture of a 73-year-old woman with pyomyositis and poststreptococcal reactive arthritis . Lancefield grouping revealed that the strain was a group G streptococcus . The Vitek system (GPI) showed that it was unidentified, and the API system (20 STREP) showed that it was 95.7% S . dysgalactiae subsp . dysgalactiae . 16S rRNA gene sequencing showed that it was a strain of S . dysgalactiae . Based on phylogenetic affiliation with 16S rRNA gene or GroEL amino acid (another bacterial gene, in addition to 16S rRNA gene, that is highly conserved) sequences, the strain is most closely related to Lancefield group C beta-hemolytic S . dysgalactiae subsp . equisimilis . PCR amplification and sequencing of the streptolysin S structural gene (sagA) and M protein gene (emm) hypervariable region showed the presence of these suspected primary virulence factors . Further studies would delineate whether the isolate is just a hemolysin-deficient variant of group G beta-hemolytic S . dysgalactiae subsp . equisimilis or a novel type of S . dysgalactiae . The present case showed that group G alpha-hemolytic S . dysgalactiae subsp . equisimilis can be associated with serious invasive infection and poststreptococcal sequelae.

J Clin Microbiol, 2003 Feb, 41(2), 601 - 7
Evaluation of semiautomated multiplex PCR assay for determination of Streptococcus pneumoniae serotypes and serogroups; Lawrence ER et al.; A semiautomated method for the determination of five serotypes and three serogroups in Streptococcus pneumoniae was developed . Primers specific for serotypes 1, 3, 14, 19F, and 23F and serogroups 6, 19, and 23 were combined in three multiplex PCRs . Products were separated by capillary electrophoresis with a 7-min run time, and a serotype or serogroup was assigned on the basis of fragment size . The method was used to test 93 clinical isolates, and all isolates of the serotypes concerned were correctly detected . The strategy would allow the detection of multiple serotypes in a single sample . Detection of additional serotypes could be included as capsule locus sequences become available.

Diagn Microbiol Infect Dis, 2003 Jan, 45(1), 63 - 7
Molecular characterization of fluoroquinolone resistant Streptococcus pneumoniae clinical isolates obtained from across Canada; Zhanel GG et al.; There is little published data detailing fluoroquinolone resistance in clinical isolates of S . pneumoniae . The purpose of this study was to characterize the resistance mechanisms of 34 fluoroquinolone-resistant S . pneumoniae clinical isolates obtained from medical centers in 8 of 10 Canadian provinces between 1997 and 2000 . The quinolone resistance determining regions of gyrA, parC, and parE from the isolates were sequenced . The isolates were evaluated for reserpine-sensitive efflux of ciprofloxacin and the new fluoroquinolones: gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin . The isolates were typed using pulsed field gel electrophoresis . The majority of the isolates were genetically unrelated . Lower level fluoroquinolone resistance (ciprofloxacin MIC 4-8 microg/ml) was associated with amino acid substitutions in ParC, while higher level resistance (ciprofloxacin MIC > or = 16 microg/ml) was associated with amino acid substitutions in both ParC and GyrA . ParE substitutions were not associated with clinical resistance . Twelve of 34 (35%) isolates demonstrated reserpine-sensitive efflux of ciprofloxacin . Efflux alone conferred low level ciprofloxacin resistance in 3 isolates . Significant reserpine-sensitive efflux of the new fluoroquinolones was not observed.

Diagn Microbiol Infect Dis, 2003 Jan, 45(1), 23 - 7
Detection of group B streptococcal bacteremia in simulated intrapartum antimicrobial prophylaxis; Hsu KK et al.; The diagnostic value of negative blood cultures from neonates whose mothers receive intrapartum antimicrobial prophylaxis for prevention of perinatal group B streptococcal disease is uncertain . We investigated whether blood culture medium containing resin designed to adsorb antibiotic improved group B streptococcal detection following simulated intrapartum antimicrobial prophylaxis . Group B streptococcus (Streptococcus agalactiae) was preincubated with varying antibiotic concentrations before inoculation into BACTEC Peds Plus resin-containing medium, BACTEC Standard, or Trek ESP 80A . In the presence of 10 mcg/mL ampicillin, detection of both low (<500 CFU/mL) and high (>500 CFU/mL) S . agalactiae inocula ranged between 75-100% of resin-containing medium bottles; detection rates in both non-resin-containing media were lower . When S . agalactiae was detected, it was detected sooner with resin-containing medium . The addition of gentamicin to ampicillin did not affect sensitivity of resin-containing medium for S . agalactiae . In our model, resin-containing medium more consistently and more rapidly detected S . agalactiae than did either of two non-resin-containing media, in the presence of antibiotic levels likely present in fetal sera following intrapartum antimicrobial prophylaxis.

J Biosci, 2002 Dec, 27(7), 703 - 14
Applications of inulin and oligofructose in health and nutrition; Kaur N et al.; Inulin and oligofructose belong to a class of carbohydrates known as fructans . The main sources of inulin and oligofructose that are used in the food industry are chicory and Jerusalem artichoke . Inulin and oligofructose are considered as functional food ingredients since they affect the physiological and biochemical processes in rats and human beings, resulting in better health and reduction in the risk of many diseases . Experimental studies have shown their use as bifidogenic agents, stimulating the immune system of the body, decreasing the pathogenic bacteria in the intestine, relieving constipation, decreasing the risk of osteoporosis by increasing mineral absorption, especially of calcium, reducing the risk of atherosclerosis by lowering the synthesis of triglycerides and fatty acids in the liver and decreasing their level in serum . These fructans modulate the hormonal level of insulin and glucagon, thereby regulating carbohydrate and lipid metabolism by lowering the blood glucose levels; they are also effective in lowering the blood urea and uric acid levels, thereby maintaining the nitrogen balance . Inulin and oligofructose also reduce the incidence of colon cancer . The biochemical basis of these beneficial effects of inulin and oligofructose have been discussed . Oligofructose are non cariogenic as they are not used by Streptococcus mutans to form acids and insoluble glucans that are the main culprits in dental caries . Because of the large number of health promoting functions of inulin and oligofructose, these have wide applications in various types of foods like confectionery, fruit preparations, milk desserts, yogurt and fresh cheese, baked goods, chocolate, ice cream and sauces . Inulin can also be used for the preparation of fructose syrups.

Proc Natl Acad Sci U S A, 2003 Feb 18, 100(4), 1661 - 6 Epub 2003 Feb 05.
Crystal structure of the plasmid maintenance system epsilon/zeta: functional mechanism of toxin zeta and inactivation by epsilon 2 zeta 2 complex formation; Meinhart A et al.; Programmed cell death in prokaryotes is frequently found as postsegregational killing . It relies on antitoxin/toxin systems that secure stable inheritance of low and medium copy number plasmids during cell division and kill cells that have lost the plasmid . The broad-host-range, low-copy-number plasmid pSM19035 from Streptococcus pyogenes carries the genes encoding the antitoxin/toxin system epsilon/zeta and antibiotic resistance proteins, among others . The crystal structure of the biologically nontoxic epsilon(2)zeta(2) protein complex at a 1.95-A resolution and site-directed mutagenesis showed that free zeta acts as phosphotransferase by using ATPGTP . In epsilon(2)zeta(2), the toxin zeta is inactivated because the N-terminal helix of the antitoxin epsilon blocks the ATPGTP-binding site . To our knowledge, this is the first prokaryotic postsegregational killing system that has been entirely structurally characterized.

Proc Natl Acad Sci U S A, 2003 Feb 18, 100(4), 1966 - 71 Epub 2003 Feb 04.
Recognition of pneumolysin by Toll-like receptor 4 confers resistance to pneumococcal infection; Malley R et al.; Streptococcus pneumoniae is one of the leading causes of invasive bacterial disease worldwide . Fragments of the cell wall and the cytolytic toxin pneumolysin have been shown to contribute substantially to inflammatory damage, although the interactions between pneumococcal components and host-cell structures have not been elucidated completely . Results of a previous study indicated that cell-wall components of pneumococci are recognized by Toll-like receptor (TLR)2 but suggested that pneumolysin induces inflammatory events independently of this receptor . In this study we tested the hypothesis that pneumolysin interacts with surface proteins of the TLR family other than TLR2 . We found that pneumolysin stimulates tumor necrosis factor-alpha and IL-6 release in wild-type macrophages but not in macrophages from mice with a targeted deletion of the cytoplasmic TLR-adapter molecule myeloid differentiation factor 88, suggesting the involvement of the TLRs in pneumolysin recognition . Purified pneumolysin synergistically activated macrophage responses together with preparations of pneumococcal cell walls or staphylococcal peptidoglycan, which are known to activate TLR2 . Furthermore, when compared with wild-type macrophages, macrophages from mice that carry a spontaneous mutation in TLR4 (P712H) were hyporesponsive to both pneumolysin alone and the combination of pneumolysin with pneumococcal cell walls . Finally, these TLR4-mutant mice were significantly more susceptible to lethal infection after intranasal colonization with pneumolysin-positive pneumococci than were control mice . We conclude that the interaction of pneumolysin with TLR4 is critically involved in the innate immune response to pneumococcus.

J Am Acad Nurse Pract, 2002 Dec, 14(12), 531 - 6; quiz 537-9
Screening strategies for group B streptococcus in the third trimester of pregnancy; Woltjen MG; PURPOSE: To identify the best screening protocol to prevent neonatal group B streptococcal (GBS) sepsis through literature review . DATA SOURCES: Selected research articles, texts, and Internet sources . CONCLUSIONS: Centers for Disease Control and Prevention (CDC), American Academy of Pediatrics (AAP), American College of Obstetricians and Gynecologists (ACOG), and American College of Nurse Midwives (ACNM) have issued guidelines describing methods to identify pregnant women at risk of intrapartum transmission of GBS to their babies . Studies have been conducted to discover the superiority of one prevention method over the other but no consensus has been reached . IMPLICATIONS FOR PRACTICE: Before widely used prevention methods, approximately 8,000 babies each year became infected with GBS; of those, 400 died and many survivors suffered life-long sequelae . Adoption of an appropriate protocol can prevent transmission of GBS from a colonized mother to her infant . Clinicians should implement either universal culture-based or risk factor-based screening guidelines for prenatal diagnosis and intrapartum prophylaxis of GBS disease.

J Biomol NMR, 2003 Jan, 25(1), 55 - 61
Myristoylation as a general method for immobilization and alignment of soluble proteins for solid-state NMR structural studies; Mesleh MF et al.; N-terminal myristoylation of the immunoglobulin-binding domain of protein G (GB1) from group G Streptococcus provides the means to bind the protein to aligned phospholipid bilayers for solid-state NMR structural studies . The myristoylated protein is immobilized by its interactions with bilayers, and the sample alignment enables orientationally dependent 15N chemical shifts and 1H-15N-dipolar couplings to be measured . Spectra calculated for the average solution NMR structure of the protein at various orientations with respect to the magnetic field direction were compared to the experimental spectrum . The best fit identified the orientation of the myristoylated protein on the lipid bilayers, and demonstrated that the protein adopts a similar structure in both its myristoylated and non-myristoylated forms, and that the structure is not grossly distorted by its interaction with the phosholipid bilayer surface or by its location in the restricted aqueous space between bilayer leaflets . The protein is oriented such that its charged sides face the phosphatidylcholine headgroups of the lipids with the single amphiphilic helix running parallel to the bilayer surface.

Caries Res, 2003 Jan-Feb, 37(1), 71 - 8
Synergy of binary poly(oxypropylene-oxyethylene) copolymers in reducing retention of Streptococcus sanguis to hydroxyapatite; Guan YH et al.; Binary poly(oxypropylene-oxyethylene) block copolymer systems have been investigated as a non-bactericidal approach to reduce the retention of an oral bacterium, Streptococcus sanguis . Using a previously validated hydroxyapatite-coated microtitre model to simulate the tooth, the performance of copolymer pairs was measured experimentally . A synergy index and an efficacy index were defined to describe the reduction of bacterial retention by the binary systems that comprise the copolymer pairs . Relationships between the synergy and efficacy indices and their associated compositions are given . The results obtained have been rationalised using a previously developed theoretical approach in conjunction with the binding energetics of species to surfaces .

Bioorg Med Chem Lett, 2003 Feb 10, 13(3), 423 - 6
A series of 2(Z)-2-benzylidene-6,7-dihydroxybenzofuran-3{2H}-ones as inhibitors of chorismate synthase; Thomas MG et al.; A series of 2(Z)-2-benzylidene-6,7-dihydroxybenzofuran-3{2H}-ones was identified as potent inhibitors of bacterial chorismate synthase . The 2'-hydroxy-4'-pentoxy analogue 33 is a potent inhibitor of Streptococcus pneumoniae chorismate synthase.

Trends Microbiol, 2002 Dec, 10(12), 575 - 80
Streptococcal beta-hemolysins: genetics and role in disease pathogenesis; Nizet V; A zone of beta-hemolysis surrounding colonies on blood-agar media is a hallmark phenotypic feature of the pathogens group A Streptococcus (GAS) and group B Streptococcus (GBS) . In each case, lysis of red blood cells reflects the action of a potent protein exotoxin . Although these toxins have been the subjects of numerous investigations over the years, their purification and molecular identification have proven elusive . These difficulties reflect the instability of hemolytic activity, as both toxins function only in the context of the bacterial surface or certain high molecular weight 'stabilizer' molecules . This review highlights the recent discoveries of two markedly distinct genetic loci, necessary and sufficient for the beta-hemolytic phenotypes of GAS and GBS, respectively . The generation of isogenic GAS and GBS beta-hemolysin-deficient mutants and their analysis using in vitro and in vivo model systems has shown that both toxins function as virulence factors in the pathogenesis of invasive infections.

J Bacteriol, 2003 Feb, 185(4), 1208 - 17
Molecular genetic analysis of a group A Streptococcus operon encoding serum opacity factor and a novel fibronectin-binding protein, SfbX; Jeng A et al.; The group A Streptococcus (GAS) sof gene encodes the serum opacity factor protein, which is capable of opacifying mammalian sera and binding at least two host proteins, fibronectin and fibrinogen . The sof gene exists in approximately 50% of clinical isolates, and there is a classical association of so-called nephritogenic strains with the opacity factor-positive phenotype . In both a type emm49 strain and a type emm12 strain, the sequences upstream of the 5' end of sof and downstream of the putative terminator were determined to be nearly identical to a region in the M type 1 genome approximately 10 kb upstream of the emm1 gene . This close genetic linkage is likely reflected in the strict correlation of opacity factor phenotype with specific emm genotypes . A new fibronectin-binding protein gene, sfbX, was discovered immediately downstream of sof in emm12 and emm49 strains and in several other sof-positive strains . The sof and sfbX genes were found to be expressed on the same transcription unit, which was correlated with the putative promoter and rho-independant terminator sequences that flank these two genes . The sfbX genes from different emm types are predicted to encode approximately 650-residue surface-bound proteins sharing 89 to 92% sequence identity . SfbX residues approximately 1 to 480 are not highly similar to those of other known proteins, with the closest match being the Staphylococcus aureus coagulase protein . The remaining portions of these proteins (residues 481 to 650) contain four putative fibronectin-binding repeats highly similar to those of other streptococcal fibronectin-binding proteins and a potential LP(X)SG cell wall anchor motif . Targeted in-frame allelic-exchange mutagenesis, complementation, and heterologous-expression studies found that serum opacification is encoded by sof alone and that sfbX encodes a fibronectin-binding function . A recombinant SfbX protein was found to bind immobilized fibronectin and to partially inhibit GAS adherence to fibronectin . The sfbX gene was found to be present only in sof-positive strains, and together these genes could influence the spectrum of tissues colonized by sof-positive GAS.

J Antimicrob Chemother, 2003 Feb, 51(2), 443 - 6
Bactericidal activity of daptomycin against Streptococcus pneumoniae compared with eight other antimicrobials; Pankuch GA et al.; A spectrum of pneumococci with varying susceptibilities to beta-lactams, macrolides and quinolones was tested for susceptibility to nine antibiotics, including the novel lipopeptide daptomycin . Daptomycin was active against all strains (MIC range </=0.5 mg/L; MIC(50) 0.125 mg/L; MIC(90) 0.25 mg/L) . All pneumococci were susceptible to vancomycin, teicoplanin, linezolid and quinupristin/dalfopristin, with MICs < 4.0 mg/L . Time-kill assays with eight strains demonstrated that daptomycin (2 x MIC) was bactericidal in seven of eight strains tested at 24 h, with >90% killing at 1 h.

J Antimicrob Chemother, 2003 Feb, 51(2), 409 - 14
Two major Spanish clones of penicillin-resistant Streptococcus pneumoniae in Portuguese isolates of clinical origin; Canica M et al.; We studied the genetic relatedness of 47 Portuguese penicillin-resistant 9V and 23F Streptococcus pneumoniae of clinical origin, using pulsed-field gel electrophoresis (PFGE) and restriction fragment length polymorphism analysis . PFGE fingerprinting showed that 24 isolates of serotype 9V and 23 isolates of serotype 23F were variants of the Spain(9V)-3 and Spain(23F)-1 clones, respectively . Fingerprinting of pbp1a, pbp2b and pbp2x genes showed that all the penicillin-resistant clones gave similar HinfI restriction patterns . In this study, serotypes 9V and 23F have different clonal origins and identical PBP genotypes, suggesting a horizontal transfer of resistance . Visual and computer-assisted analysis of PFGE patterns correlated well (r = 0.983).

J Antimicrob Chemother, 2003 Feb, 51(2), 333 - 7
Significant increase in the prevalence of erythromycin-resistant, clindamycin- and miocamycin-susceptible (M phenotype) Streptococcus pyogenes in Spain; Alos JI et al.; In 1998 we conducted a multicentre study in Spain on the susceptibility of Streptococcus pyogenes isolates to different 14-, 15- and 16-membered macrolides and clindamycin, in which the number of strains examined was proportional to the number of inhabitants in each geographical area . The aim of the present work was to re-examine the antimicrobial susceptibility of S . pyogenes in 2001, using the same methodology and centres as in 1998, to determine the different susceptibility phenotypes to macrolides-lincosamides, and to compare the results from the 2 years by statistical tests . A total of 529 unique isolates of S . pyogenes, collected in 21 laboratories, were studied . Throat swabs provided 417 isolates (78.8%), and the remaining 112 were from other sources . Four hundred and thirty-five (82.2%) were isolated from children and 94 (17.8%) from adults . One hundred and fifty-seven (29.7%) of the isolates were resistant to erythromycin and azithromycin, whereas resistance to miocamycin, a 16-membered macrolide, was 1.5% . The prevalence of resistance to clindamycin was 1.3% . The majority (98.7%) of the 157 erythromycin-resistant strains presented the M phenotype . When we compared the results obtained in 1998 and 2001, we observed a statistically significant increase in resistance to erythromycin and azithromycin (P = 0.02, chi(2) test), but not to clindamycin or miocamycin (P = 0.47, chi(2) test with Yates' correction) . The significant increase in the prevalence of resistance to some macrolides of S . pyogenes in Spain underscores the need for continuous surveillance of antimicrobial resistance in this species.

Indian J Pathol Microbiol, 2001 Jan, 44(1), 37 - 9
Vaginal carriage of group B Streptococcus in infertile women; Verghese S et al.; From May, 1999 to April, 2000, 256 high vaginal swabs were culture from asymptomatic infertile women attending the out-patient department of the Institute of Reproductive Medicine . 41 strains of Streptococcus agalactiae were isolated from 33 patients (12.89%) . Five patients had repeated isolations even after adequate therapy.

Lancet Infect Dis, 2003 Feb, 3(2), 71 - 8
Efficacy of polysaccharide pneumococcal vaccine in adults in more developed countries: the state of the evidence; Mangtani P et al.; We review studies on the efficacy against disease caused by Streptococcus pneumoniae of the 23-valent polysaccharide pneumococcal vaccine in adult populations in the more developed countries . Meta-analyses of primary vaccine trials have attempted to reduce uncertainty from lack of power . Vaccine efficacy calculated from studies in South African gold-miners and in Papua New Guinea, with high attack rates and differing serotype patterns, cannot automatically be applied to more developed countries . Meta-analyses will overestimate a protective effect if this clinical heterogeneity is ignored . Meta-analyses limited to trials in the more developed setting show no protective effect against pneumococcal pneumonia and a non-significant protective effect against bacteraemia . Lack of a specific diagnosis limits the ability to detect a protective effect against pneumococcal pneumonia . Most, but not all, observational studies confirm a protective effect against bacteraemia . An effect on mortality in more developed countries has yet to be documented.

Vaccine, 2003 Mar 7, 21(11-12), 1112 - 7
Construction of designer glycoconjugate vaccines with size-specific oligosaccharide antigens and site-controlled coupling; Wang JY et al.; Coupling of carbohydrate antigens to protein carriers is a typical approach to enhancing the immunogenicity of carbohydrate-based vaccines . Glycoconjugates with well-defined structures are needed for studies defining the structural variables that govern antibody responses . We report a chemical strategy for preparation of an array of glycoconjugates containing saccharides of desired molecular sizes by selective depolymerization of bacterial polysaccharides and chemically controlled site-specific coupling . As an example, we synthesized and evaluated an oligosaccharide-based vaccine against type III group B Streptococcus .

Epidemiol Infect, 2002 Dec, 129(3), 491 - 7
Nasopharyngeal carriage of resistant pneumococci in young South Indian infants; Coles CL et al.; Streptococcus pneumoniae is the leading bacterial cause of life-threatening infections in infants . Although antibiotic resistance affects management of pneumococcal infections, few data on patterns of resistance are available for India . We examined nasopharyngeal carriage of antibiotic-resistant pneumococci in 464 South Indian infants between 2 and 6 months . Newly acquired serotypes were screened for susceptibility to cotrimoxazole, erythromycin and penicillin using disk diffusion . Cumulative prevalence of pneumococcal carriage rose from 53.9% at 2 months to 70.2% at 6 months . The prevalence of strains that were not susceptible to penicillin, cotrimoxazole and erythromycin was 34, 81.1 and 37.2%, respectively . Carriage of erythromycin non-susceptible strains declined significantly between ages 4 months and 6 months (44.1 vs . 10.7%) . More than 87% of the isolates screened were non-susceptible to > or = 1 antibiotic . Serogroups/types that were most frequently non-susceptible to 1 or more antibiotics were 6, 9, 14, 19 and 23 . Less than 1% of the isolates were multi-drug resistant . Widespread use of antibiotics in South India has resulted in S . pneumoniae becoming non-susceptible to some commonly used antibiotics . Monitoring trends in antibiotic susceptibility and making antibiotics available only through prescription from a health care worker may slow the spread of resistant pneumococci and improve management of pneumococcal infections in South India.

Ginecol Obstet Mex, 2002 Oct, 70, 521 - 6
{Clinical and demographic profile of patients with gyneco-obstetric disease colonized by Streptococcus agalactiae}; Carrasco-Morales I et al.; OBJECTIVE: To describe demographics and clinical features in women with vaginal colonization with Streptococcus agalactiae attended in a gyneco-obstetric hospital . METHODS: Descriptive study of 118 women with isolation of Streptococcus agalactiae in cervical swab during January 1992 to December 1998 . Major patient features were obtained in retrospective revising their chart and were classified in demographic, gyneco-obstetrical and clinical characteristics . Statistical analyses were performed with descriptive statistics using central tendency measurements and dispersion, frequencies, rates and proportions with all different variables . RESULTS: Mean age was 31 +/- 11 years; 44 (37.3%) received attention because of sterility, 37 (31.4%) were pregnant, 26 (22%) had any other gynecological disease and, 11 (9.3%) were in a group of high pregestational risk . One hundred eleven (94.1%) were sexually active, starting at a mean age of 20.9 +/- 4.3 . GBS was the only microorganism isolated in 70 patients (59.3%) . A concomitant cervicovaginal infection was identified in 22 (18.6%) patients . A sexual transmitted disease was present in 25 (21.2%) patients, with isolation of human papilomavirus (HPV), M . hominis, C . trachomatis y T . vaginalis . Fifty-five patients had a concomitant illness: 24 with endocrine disease, 12 cardiovascular pathology and 10 with oncologic disease . CONCLUSIONS: Vaginal colonization of mexican women by GBS is low . However, clinical and demographics characteristics are required to identify these women easily, because of the importance of maternal and infant infection by this organism.

Wei Sheng Wu Xue Bao, 2002 Feb, 42(1), 105 - 9
{Analysis of virulence-related proteins of Streptococcus suis type 2 from swine Streptococcus isolated in China}; Ou Y et al.; Virulence-related proteins, muraminidase-released protein (MRP) and extracellular factor (EF) of Streptococcus suis type 2, were extracted from Jiangsu Isolate HA9801 and were used as antigens for preparation of antibodies . Bacterium cell envelope proteins and extracellular proteins of swine Streptococcus strains including 17 Chinese isolates, 1 German strain and 1 human isolate of Streptococcus suis type 2, were analyzed by SDS-PAGE and immunoblotting using the above antibodies, 11 strains produced MRP and 10 strains possessed EF or EF . They exist four phenotypes: MRP+ EF+ (8/19), MRP+ EF (1/19), MRP+ EF- (1/19), MRP- EF- (10/19).

J Antimicrob Chemother, 2002 Dec, 50 Suppl S2, 93 - 100
New strategies to overcome antimicrobial resistance in Streptococcus pneumoniae with beta-lactam antibiotics; Aguilar L et al.; The worldwide epidemic of antibiotic resistance in Streptococcus pneumoniae appears to advance inexorably and the measures taken to date to contain its progression have not been successful . Consideration should be given to the complex relationship between antibiotic consumption and resistance to the drug administered and also to other agents in the same and other antibiotic groups . We propose an integrated triple strategy that maximizes the use of the current antibiotic arsenal and is designed to curb the spread of resistance in S . pneumoniae . There are three main parts to this strategy: (i) reduction of prescribing, with particular emphasis on those drugs whose consumption has been shown to correlate strongly with resistance; (ii) development of new formulations or dosing schedules of those drugs whose pharmacodynamic parameters are better suited to cope with highly resistant strains; and (iii) encouragement of the use of antibiotics with the maximal capability of bacterial eradication . We believe such a strategy would reduce the spread of resistance both in the current ecological situation and in the post-pneumococcal vaccination era to come . Of all current antibiotics amoxicillin meets the above requirements, and seems to be the least ecologically disturbing oral antibiotic with regard to resistance in S . pneumoniae.

J Antimicrob Chemother, 2002 Dec, 50 Suppl S2, 83 - 6
Beta-lactam activity against resistant pneumococcal strains is enhanced by the immune system; Casal J et al.; Pandemic resistance in Streptococcus pneumoniae is compromising antibiotic activity . Antibiotics that act on the cell wall, such as beta-lactams, may have a combined effect with the immune system against S . pneumoniae, since both act on the bacterial envelope . This combined effect can be studied in vitro or in vivo with respect to bacterial killing, since lysis is the end-point of both beta-lactams and the immune system . We review here the in vitro increase in the bactericidal activity of aminopenicillins by non-specific immunity (complement and polymorphonuclear leucocytes) . Few data are available on the collaboration of specific immunity and beta-lactams . We also review the effect of the presence of specific antibodies on the in vivo T > MIC needed for the therapeutic efficacy of amoxicillin, and on blood bacterial clearance in animal models . The effect that immunity has on pharmacodynamic parameters, such as T > MIC, in non-human studies may be used as a tool to predict the effect of these pharmacodynamic variations in overcoming resistance and its selection, in the context of increasing the use of pneumococcal conjugated vaccines.

J Antimicrob Chemother, 2002 Dec, 50 Suppl S2, 75 - 81
From ecological reservoir to disease: the nasopharynx, day-care centres and drug-resistant clones of Streptococcus pneumoniae; De Lencastre H et al.; Several lines of epidemiological and microbiological studies point to the multiple and critical roles of the nasopharynx of children-particularly those of pre-school age and attending day-care centres (DCCs)-in the emergence and spread of drug-resistant Streptococcus pneumoniae (DRP) . A systematic yearly surveillance of the nasopharyngeal flora of children attending DCCs has been carried out in Lisbon since 1996 . Molecular typing of several hundred DRP isolates showed that the great majority of DRP were represented by a relatively few clonal types that were frequently carried by many children in geographically distant DCCs and over several years of surveillance . The same epidemic DRP clones were also frequent among pneumococci causing both paediatric and adult disease worldwide . Penicillin-resistant pneumococci carry sequences of heterologous origin in their pbp genes and also in the recently identified murM: a gene essential for expression of penicillin resistance and for the unique cell wall structure of penicillin-resistant pneumococci . Virtually all DRP express only a limited number (five or six) of the very large genetic repertoire (up to 90) of serotypes available for this bacterial species and the serotypes of drug-resistant strains happens to be the same as the serotypes of drug-susceptible pneumococci that most frequently colonize pre-school age children . These observations strongly suggest that the nasopharynx of children is an important global ecological reservoir of DRP and may also play a critical role as the favoured anatomical site for the evolution of DRP.

J Antimicrob Chemother, 2002 Dec, 50 Suppl S2, 51 - 8
Pharmacodynamic and kinetic basis for the selection of pneumococcal resistance in the upper respiratory tract; Soriano F et al.; The oropharynx is both the reservoir where antibiotic-resistant Streptococcus pneumoniae strains are selected and the focus for further spread of these organisms . In order to select antibiotic-resistant organisms, the antibiotic must be able to eradicate the susceptible population . How an antibiotic acts on oropharyngeal flora is not fully understood, although data on salivary antibiotic concentrations could be useful for establishing some correlation . Many beta-lactam antibiotics are very active against S . pneumoniae, and although their saliva concentrations are very low, there may be enough to eradicate the majority of beta-lactam-sensitive strains . Other antibiotics achieve salivary concentrations in the range 10-30% of serum concentrations (erythromycin, clindamycin, doxycycline and rifampicin), and are also able to eradicate the antibiotic-susceptible population . Antibiotics achieving higher salivary concentrations (>/=40% of the serum levels) are not very active against S . pneumoniae (ciprofloxacin) or are able to eradicate antibiotic-sensitive and -intermediate strains (clarithromycin, azithromycin and telithromycin) . Only antibiotics for which there are no highly resistant pneumococcal strains, for instance some beta-lactams administered at very high dose and for a short course, are associated with a lower risk of antibiotic resistance selection . To diminish the risk, the antibiotics should be dosed in order to obtain inhibitory quotients (maximal serum concentration/MIC ratios) >/= 4, which depends not only on the antibiotic concentration achieved but also on the lack of highly resistant organisms.

J Antimicrob Chemother, 2002 Dec, 50 Suppl S2, 45 - 9
Nasopharyngeal carriage of Streptococcus pneumoniae: a review of the potential role of pharmacokinetics and pharmacodynamics; Wise R; Much antibiotic prescribing is based upon irrational practice rather than scientific principles . The advent and the better understanding of the pharmacokinetics and pharmacodynamics of antimicrobials are slowly leading to a change whereby antibiotics are prescribed with a better rationale . The fundamental understanding of the pharmacokinetics of the antimicrobial, for example how well it is absorbed, metabolized, distributed and eliminated from the body, should lead to an appreciation of the correct dosing interval . Pharmacodynamic factors, in particular, appreciation of the MIC of an antimicrobial for an infecting pathogen and whether time-independent or -dependent killing occurs, will also have a profound influence upon how an antimicrobial is used . This review attempts to consider these features as they apply to nasopharyngeal carriage of Streptococcus pneumoniae . The reason for the dosing and dosing frequency of a number of agents is discussed and an attempt is made to point the way to more judicious antibiotic prescribing so as to maximize clinical efficacy yet minimize the possibility of resistance emerging during therapy.

J Antimicrob Chemother, 2002 Dec, 50 Suppl S2, 39 - 43
Importance of dose and duration of beta-lactam therapy in nasopharyngeal colonization with resistant pneumococci; Canet JJ et al.; Antibiotic use greatly influences the nasopharyngeal carriage of drug-resistant Streptococcus pneumoniae and is considered to be one of the most important risk factors for carriage of such organisms . Several studies have shown a reduction in the prevalence of resistant strains following reduced antibiotic consumption . This indicates that it may be possible to reduce resistance rates by changing prescribing patterns . Studies suggest that antibiotics present at low levels tend to select strains with low-level penicillin resistance, that intermediate antibiotic levels may pose the danger of selection of pneumococci with high-level penicillin resistance and that attainment of high levels of antibiotics may reduce the selective pressure for penicillin resistance . High-dose beta-lactam (amoxicillin) therapy has been shown to reduce the selection of resistant pneumococci in the nasopharynx . Likewise, short-course antibiotic therapy has reduced colonization by resistant strains . Finally, the effect of the antibiotic appears to differ according to the beta-lactam prescribed . Studies suggest that selection by cephalosporins occurs at higher frequencies than that by amoxicillin; this may be explained by the reduced activity of cephalosporins against penicillin-resistant S . pneumoniae.

J Antimicrob Chemother, 2002 Dec, 50 Suppl S2, 27 - 37
Antibiotic consumption and resistance selection in Streptococcus pneumoniae; Baquero F et al.; Selection of antibiotic-resistant Streptococcus pneumoniae is an inescapable consequence of antibiotic use . The correlation between antibiotic consumption and selection of resistant organisms can be shown at every ecological level: patient, community, region or country . In the case of multiple resistance, the intensity of antibiotic selection is increased . However, different antibiotics may exert different selective powers . Because of this, co-selection of macrolide and beta-lactam resistance is an asymmetrical phenomenon: macrolides select more efficiently strains resistant to both macrolides and beta-lactams than aminopenicillins . The difference in rates of antibiotic resistance is also influenced by the local spread of susceptible or resistant clones; it is suggested that under mild antibiotic selection, the susceptible organisms that are more fit for host-to-host transmission could be favoured . Subsequent acquisition of resistance in these clones may rapidly increase the prevalence of resistance, and that may lead to an increase in the use of antibiotics . The reasons for antibiotic resistance are mainly the reasons explaining antibiotic consumption . A number of possible sociobiological determinants of antibiotic consumption can be identified: genetic factors in the human populations (for instance, involving different symptomatic types of infection), cultural factors and attitudes of patients towards antibiotics, sociological factors or public health factors, including incidence of other infectious diseases in the human population . Only 'excess' in the use of antibiotics should be controlled; for such a purpose, the concept, 'appropriate demand for antibiotics' (ADA) is proposed.

J Antimicrob Chemother, 2002 Dec, 50 Suppl S2, 7 - 12
Antimicrobial resistance: a class effect?
Prieto J, Calvo A, Gomez-Lus ML.
Antibiotic use has led to increased resistance to certain group markers: penicillin, erythromycin and ciprofloxacin for beta-lactams, macrolides and quinolones, respectively . The influence of resistance to markers in decreasing susceptibility to the drugs included (on the basis of chemical structure) in the corresponding antibiotic group can be defined as 'resistance class effect' . In the case of macrolides, this effect is dependent on the prevalent resistant phenotype among the isolates of the target bacteria: the class effect exists completely if the mechanism of resistance is constitutive MLS(B) (all macrolides are affected by resistance to erythromycin), and only partially if the mechanism is the efflux M phenotype (all but 16-membered macrolides are affected) . In Spain, the first case is exemplified by Streptococcus pneumoniae and the second by Streptococcus pyogenes . For beta-lactams and quinolones, resistance to the group markers results in large decreases in the antimicrobial activity of the less potent members of the group, penicillin being a better driver of resistance for oral cephalosporins than for aminopenicillins, and ciprofloxacin being a better driver for older rather than for the newer quinolones, which have enhanced anti-pneumococcal activity . Empirical prescription guidelines based on the pharmacoepidemiology of resistance, recommending the use of potent drugs that are less influenced by resistance to the marker, may help to counter the spread of resistance in the community.

J Antimicrob Chemother, 2002 Dec, 50 Suppl S2, 1 - 5
The successful clone: the vector of dissemination of resistance in Streptococcus pneumoniae; Klugman KP; A small number of pneumococcal clones dominate the population of antibiotic-resistant pneumococci . The emergence of fluoroquinolone resistance in these clones predicts the dissemination of fluoroquinolone resistance in countries where the clones are present and community use of fluoroquinolones for respiratory infections is common . The molecular basis of resistance to a number of classes of antimicrobials can be used to predict the likelihood of dissemination of the resistance genes.

Ann Cardiol Angeiol (Paris), 2000 Oct, 49(7), 403 - 6
{Isolated primary streptococcal tricuspid endocarditis . A case report}; Monnier G et al.; The authors report a new case of primitive isolated endocarditis of the tricuspid valve . The microorganism responsible, Streptococcus sanguis, is unusual in its localization and in this environment . The uncomplicated evolution poses the problem of deciding what action should be taken vis-a-vis the persistence of an important isolated vegetation after effective antibiotic treatment . Therapeutic abstention was chosen rather than surgical intervention in light of the literature . A spontaneous pulmonary embolic migration of the vegetation was effectuated 3 weeks after termination of the antibiotic treatment without pulmonary or hemodynamic complications.

J Dent, 2002 Sep-Nov, 30(7-8), 325 - 31
Effects of nitrite and nitrate on the growth and acidogenicity of Streptococcus mutans; Radcliffe CE et al.; It is hypothesised that exogenous nitrite acidified by metabolic products of acidogenic bacteria in the mouth will be converted to products which inhibit growth of the bacteria in question which contribute to dental caries . OBJECTIVES: The aims of this study were (1) to test the activity of both sodium nitrate and sodium nitrite at differing concentrations on the ability of Streptococcus mutans to lower the pH of its surroundings and hence (2) to determine whether either nitrate or nitrite might be bactericidal or bacteriostatic against S . mutans . METHODS: S . mutans NCTC 10449(T) was cultured in a liquid medium to which either sodium nitrate or sodium nitrite was added to a final concentration of 0.0, 0.2, 2.0, 20 or 200 mM, of which the first acted as a test substance negative control . After 24 h, the cultures were streaked onto agar to test for growth and the remaining culture used for pH measurement . The Mann-Whitney U-Test was used for statistical comparison of pH values . RESULTS: Nitrite at concentrations of 20 and 200 mM had a highly significant inhibitory effect (p < 0.001) on the ability of S . mutans NCTC 10449(T) to lower pH . Moreover, bacteria that had been subjected to these levels of nitrite were unable to recover on solid medium . Nitrate had no such effect on either the growth of the bacteria or on their ability to lower pH . CONCLUSIONS: It is concluded that nitrite, at final concentrations of either 20 or 200 mM, is both bactericidal and anti-acidogenic with respect to S . mutans, while lower concentrations of nitrite and all concentrations of nitrate are ineffective . Nitrite might be worthy of consideration as a mouth-rinse constituent .

Equine Vet J, 2003 Jan, 35(1), 72 - 7
Occurrence of infectious upper respiratory tract disease and response to vaccination in horses on six sentinel premises in northern Colorado; Mumford EL et al.; REASONS FOR PERFORMING STUDY: Horses vaccinated against common agents of infectious upper respiratory disease (IURD) may not have detectable serum antibody and may not be protected from clinical disease . OBJECTIVES: The objectives of this study were to 1) investigate the serological response of horses to vaccination against influenza virus (H3N8 and H7N7) and equine herpesviruses (EHV) in a field setting and 2) evaluate associations among vaccination status, serum antibody concentrations, and occurrences of IURD in monitored horses . METHODS: In this study, horses on 6 Colorado premises were vaccinated parenterally against influenza virus and EHV, and serological response evaluated . Horses were monitored, and biological samples collected from individuals with clinical IURD and control horses . RESULTS: Of 173 horses, 61 (35.3%), 21 (12.1%) and 4 (2.3%) seroconverted in response to vaccination against EHV, influenza virus H7N7 and influenza virus H3N8, respectively . CONCLUSIONS: Outbreaks of IURD in study horses were associated with influenza virus H3N8 and Streptococcus equi infection, and serological response to vaccination with conventional products was poor . POTENTIAL RELEVANCE: These results confirm that horses may not respond with detectable serological responses to conventional vaccination against common respiratory viruses and, therefore, suggest that alternate methods of protecting horses against common respiratory viruses should be sought.

Dis Aquat Organ, 2002 Dec 10, 52(3), 199 - 205
Infection of barramundi Lates calcarifer with Streptococcus iniae: effects of different routes of exposure; Bromage ES et al.; The use of various challenge techniques has allowed the formation of a hypothesis for the mode of infection of Streptococcus iniae in barramundi . A bacterial dose of 1 x 10(3) colony forming units (cfu), corresponding to the LD50, delivered orally to barramundi could initiate the sub-acute form of the disease observed at the farms . The acute form of the disease could be initiated through bath exposure to the pathogen . S . iniae was equally as infective in freshwater, saltwater or when fish were subject to skin trauma prior to exposure, with LD50 values of 3.2 x 10(4), 2.0 x 10(4), 3.2 x 10(4) cfu, respectively, when observed over a 10 d period . It is suggested that sub-acute infection occurs orally, with mass mortalities occurring through the increased presence of the bacterium in the environment.

J Infect Dis, 2003 Jan 15, 187(2), 330 - 3 Epub 2002 Dec 19.
Immune response to capsular polysaccharide and surface proteins of Streptococcus pneumoniae in patients with invasive pneumococcal disease; Zysk G et al.; The immune response to pneumococcal capsular polysaccharides (CPSs) and to the pneumococcal surface proteins cell wall-associated serine proteinase A (PrtA), pneumococcal surface protein A (PspA), and Streptococcus pneumoniae pullulanase A was evaluated in 45 patients with invasive pneumococcal disease compared with healthy adults . In serum from patients with meningitis and pneumonia, CPS antibody levels were low, compared with healthy adults; antibody levels did not differ between groups and did not change between phases . Levels of immunoglobulin G directed against the investigated pneumococcal surface proteins in patients with invasive pneumococcal disease were in the same range as in healthy adults . However, median PrtA and PspA antibody levels tended to increase during early convalescent phase . Low levels of CPS antibody, rather than of antibodies directed against the pneumococcal surface proteins, may predispose to invasive pneumococcal infection.

Br J Plast Surg, 2002 Dec, 55(8), 682 - 4
Streptococcal myositis: a lesson; Dalal M et al.; Streptococcal myositis is a rare, often fatal, acute infection of the muscle, caused by an invasive group A beta-haemolytic streptococcus . It is characterised by muscle necrosis without abscess formation, and, in contrast to necrotising fasciitis, does not primarily affect the subcutaneous tissue or skin . A young adult male presented with streptococcal myositis initially affecting the rectus femoris muscle of his left thigh . The symptoms, signs and management are discussed . Particular emphasis is given to the benefits of emergency CT scans to diagnose and delineate the extent of the disease . These scans may need to be repeated if the disease progresses . The four cornerstones of management are: early diagnosis using emergency CT scans; high-dose intravenous antibiotics; early aggressive surgical debridement; and intensive fluid and nutritional support.

Enferm Infecc Microbiol Clin, 2003 Jan, 21(1), 30 - 41
{Role of linezolid in antimicrobial therapy}; Carmona PM et al.; The progressive emergence of multi-resistant gram-positive strains has prompted the search for new molecules (quinolones, streptogramins, oxazolidinones, ketolides, glycopeptides, daptomycin) to add to the current therapeutic arsenal . Linezolid, the first commercially available member of the oxazolidinone family, has evidenced activity against multi-resistant gram-positive strains (methicillin-resistant Staphylococcus aureus, S . aureus with decreased glycopeptide sensitivity, vancomycin-resistant Enterococcus spp., Streptococcus pneumoniae with decreased sensitivity to penicillin and cephalosporins), thereby providing a new option for treating infections by these microorganisms . This work reviews the microbiologic and pharmacologic aspects of this agent in order to establish its position among the available options for antimicrobial chemotherapy.

Enferm Infecc Microbiol Clin, 2003 Jan, 21(1), 12 - 9
{Antibiotic resistance in 622 Streptococcus pneumoniae isolated from blood and cerebrospinal fluid in 33 Spanish hospitals participating in the European Antimicrobial Resistance Surveillance System (2000)}; Oteo J et al.; INTRODUCTION: In 1998 the European Union founded the European Antimicrobial Resistance Surveillance System (EARSS) for the control of antimicrobial resistance in invasive pathogens . This report present the results obtained for S . pneumoniae in the year 2000 in Spain . METHODS: Participants included 33 hospitals covering approximately 25% of the Spanish population . The laboratories carried out isolation, identification and sensitivity studies with their usual methods . Quality control was performed by the UK National External Quality Assurance Scheme (NEQAS) . A form was filled out with clinical information on the patient and data on the hospital, department and specimen isolated . This information was entered in a central database for analysis and validation by the Whonet.5 program . RESULTS: Invasive S . pneumoniae was isolated in 622 patients . Overall incidence was 6.4 cases/100,000 inhabitants . Among the strains isolated, 33.1% (CI 95%: 29.6-37) showed resistance to penicillin (22.2% intermediate; 10.9% resistant); 11% showed resistance to cefotaxime (10.1% intermediate; 0.9% resistant); and 21.1% were resistant to erythromycin . Erythromycin resistance was 7% in penicillin-sensitive strains and 46.4% in penicillin-resistant strains (p < 0.001) . A total of 51.7% of strains were resistant to penicillin in children < or = 4 years old, as compared to 29% in patients > 4 years old (p < 0.001) . A ciprofloxacin MIC > 2 mg/L was found for 2.4% of isolates . CONCLUSIONS: Penicillin resistance in invasive S . pneumoniae in Spain is among the highest in the European Union . The decrease in sensitivity to penicillin was significantly associated with cefotaxime and erythromycin resistance . Children < or = 4 years old have a significantly higher risk than adults of acquiring infection with strains resistant to penicillin, cefotaxime and erythromycin.

Enferm Infecc Microbiol Clin, 2003 Jan, 21(1), 7 - 11
{Epidemiologic study of infection by resistant gram-positive bacteria (G + R Study)}; Betriu C et al.; INTRODUCTION: This epidemiologic study was performed to obtain the following information: incidence of the main multiresistant gram-positive microorganisms (coagulase-negative staphylococci, Staphylococcus aureus, Streptococcus pneumoniae and enterococci) in Spanish hospitals, the type of infections they cause and the most highly affected hospital areas, as well as some antimicrobial resistance patterns, specifically S . aureus to methicillin and S . pneumoniae to penicillin . METHODS . Among the various Spanish autonomous regions, 104 hospitals and 446 doctors belonging to several medical fields participated in the study . Patients admitted to the following departments were included: Intensive Care, Infectious Diseases, Internal Medicine, Hematology, Surgery, Pneumology, Oncology and Pediatrics . The study was performed between December 2000 and March 2001, using two one-week time periods . RESULTS: Staphylococci were the most frequently isolated microorganisms, comprising more than 70% of the etiologic agents found . Enterococci were responsible for 17 to 20% of the infections evaluated . Among the total, 35.3% of S . aureus were methicillin-resistant and 28.6% of pneumococci were penicillin-resistant . The most frequent infections were bacteremias, followed by skin and soft tissue infections, and lower respiratory tract infections . CONCLUSIONS: This study confirms the high percentage of methicillin-resistant S . aureus and penicillin-resistant S . pneumoniae present in our country . It also shows that among gram-positive microorganisms, there is a clear predominance of staphylococci as pathogenic agents.

Clin Sci (Lond), 2003 Jun, 104(6), 615 - 25
Modulation of neutrophil complement receptor 3 expression by pneumococci; Williams JH Jr et al.; Complement receptor 3 (CR3; CD18/CD11b) plays an important role in the recognition and clearance of Streptococcus pneumoniae (pneumococci) by neutrophils . The purpose of the present study was to characterize the modulation of CR3 surface expression on neutrophils exposed to pneumococci and to assess its functional significance . CR3 was detected with fluorescent phytoerythrin-labelled anti-CR3 (CD11b) antibodies, quantified with a fluorescence cell counter (FACS) and localized by confocal fluorescence microscopy . Uptake of fluorescent FITC-labelled pneumococci was quantified by FACS . Whole blood from healthy volunteers was exposed at 37 degrees C to killed whole type III Streptococcus pneumoniae (KSP; 10(8)/ml) or to a positive control ( Escherichia coli lipopolysaccharide) that enhanced CR3 surface expression on neutrophils to a comparable extent . Varying the concentration of KSP between 10(5) and 10(8) organisms/ml progressively augmented CR3 surface expression measured at 1 h, whereas the response declined at 10(9)/ml . The diminished response to 10(9) KSP/ml proved to be time-dependent, with surface CR3 up-regulated maximally within 5 min, and down-regulated thereafter . Labelling of CR3 during exposure demonstrated accelerated receptor sequestration, and confocal fluorescence microscopy demonstrated internalized CR3 . Cooling to 16 degrees C, to inhibit the up-regulation of CR3 surface expression, also inhibited the uptake of FITC-labelled KSP and morphological changes . Accelerated down-regulation of surface CR3 expression by exposure to 10(9)/ml unlabelled KSP diminished the uptake of labelled KSP added subsequently . In contrast, lipopolysaccharide-induced up-regulation of CR3 expression increased the uptake of labelled KSP . Together, these experiments reveal dynamic modulation of CR3 expression on the surface of neutrophils exposed to pneumococci and a functional correlate of this modulation . Thus neutrophil expression of CR3 changes dynamically in response to exposure of neutrophils to progressively higher concentrations of pneumococci, conditions that mimic early neutrophil recruitment to densely infected lung tissue in acute pneumococcal pneumonia.

Wei Sheng Wu Xue Bao, 1998 Oct, 38(5), 376 - 80
{Part of biological activity of peptidoglycan from Streptococcus lactis SB900}; Meng F et al.; Peptidoglycan of Streptococcus lactis SB900(LABPG) was isolated . It's chemical composition was analyzed and part of biological activity was examined . The PG contained 9.84% protein, 0.871 mumol/m NAG, 1.14 mumol/mg NAM . The amino acids of relatively high concentrations were Ala, Glu, Asp and their concentrations were 1.046, 0.775, 0.304 mumol/mg respectively . Using mice as subject, the animal experiment confirmed that LABPG was non-toxic and safe . Effect of i.p . LABPG 0.5 mg/mouse on the phagocytic function were studied . It was suggested that the phagocytic activity of PM phi had markedly enhanced, the activity of serum lysozyme was increased significantly . YC-Rosette experiment suggested that the activity of C3b receptors of PM phi were increased and the YC-Rosette forming ratio were higher than controls . The difference was significant by statistical analysis . Therefore, it is considered that LABPG was able to activate M phi and improve immune function in mice.

Proteomics, 2003 Jan, 3(1), 29 - 35
Application of immunoproteomics to analysis of post-translational processing of the antiphagocytic M protein of Streptococcus; Romer TG et al.; Post-translational modification of the antiphagocytic M1 protein of Streptococcus pyogenes can influence its binding properties for human immunoglobulin G subclasses and its invasive potential . Current methods of monitoring this modification event involve N-terminal sequencing and are cumbersome, slow and not amenable to routine analysis . In this study we demonstrate that surface enhanced laser desorption/ionization-time of flight mass spectrometry can be used to monitor modification of the M1 protein by the secreted bacterial cysteine protease, SpeB . This method, when combined with a specific antibody capture step provides a specific, rapid and sensitive assay for key virulence factors of the important human pathogen Streptococcus pyogenes.

Mil Med, 2003 Jan, 168(1), 1 - 6
An outbreak of pneumococcal pneumonia among military personnel at high risk: control by low-dose azithromycin postexposure chemoprophylaxis; Sanchez JL et al.; In the winter of 1998-1999 an outbreak of pneumococcal pneumonia occurred among Ranger students undergoing high-intensity training . Thirty pneumonia cases (attack rate = 12.6%) were identified among a group of 239 students . Eighteen students were hospitalized; Streptococcus pneumoniae-positive cultures were detected in 11 (61.1%) of these 18 hospitalized cases . Pneumococci were also identified in throat swabs of 30 (13.6%) of 221 nonhospitalized students surveyed . Serum antipneumolysin seroconversions were detected in 30 (18.3%) of 164 students tested . An association between development of serum antipneumolysin antibody and pneumococcal pharyngeal carriage/colonization was found . Of 30 seroconverters, eight (26.7%) had S . pneumoniae-positive cultures compared with only 17 (12.7%) of 134 nonseroconverters (relative risks = 2.02, 95% confidence interval = 1.02-4.02, p = 0.05) . The outbreak was controlled by administrating lowdose, oral azithromycin prophylaxis (250 mg weekly for 2 weeks) and was associated with a 69% reduction in pneumococcal carriage and a 94% reduction in pneumonia rates.

Hua Xi Yi Ke Da Xue Xue Bao, 2000 Sep, 31(3), 362 - 4
{A comparative study on the capacities of different strains of Streptococcus sanguis for P-aminobenzoic acid production}; Li L et al.; This study was intended to compare the capacities of different strains of Strep, sanguis for P-Aminobenzoic acid (PABA) production . The synthesis of PABA during the growth of four strains of Strep . sanguis was measured by the reversed-phase high-performance liquid chromatographic method . The results showed that the concentrations of PABA synthesized by S . sanguis 10556, S . sanguis 10557, S . sanguis S34 and S . sanguis H7-4 . Were 1.979 +/- 0.081 micrograms/ml, 1.383 +/- 0.193 micrograms/ml, 1.983 +/- 0.052 micrograms/ml and 1.032 +/- 0.229 micrograms/ml, respectively, and in term of PABA concentration, S . sanguis 10556 was significantly different from S . sanguis 10557 and S . sanguis H7-4; S . sanguis S34 was significantly different from S . sanguis 10557 and S . sanguis H7-4 . No significant difference was found between S . sanguis 10556 and S . sanguis S34, nor between S . sanguis 10557 and S . sanguis H7-4, either . In conclusion, the method is simple, rapid and accurate . S . sanguis did synthesize PABA, and the difference in ability for PABA formation existed among the four strains of S . sanguis . This study is helpful to researches on the symbiosis between S . sanguis and S . muntans and to determination of their role in the microbial homeostasis of dental plaque.

Postgrad Med, 2003 Jan, 113(1), 42 - 4, 47-8, 52-4
Penicillin resistance in pneumococcal pneumonia . Antibiotics with low resistance potential are effective and pose less risk; Cunha BA; Antibiotic resistance is a potential problem around the world . Among the bacteria that cause community-acquired pneumonia (CAP), resistance in Streptococcus pneumoniae is a primary concern . Resistance can occur through genetic mutations in the bacterial strain itself or can be acquired through use of some antibiotics that have a high resistance potential . In this article, Dr Cunha explores the misperceptions about antibiotic resistance and its occurrence, as well as the most appropriate therapy for CAP in the clinical setting.

J Pediatr Hematol Oncol, 2003 Jan, 25(1), 46 - 55
Chlamydia pneumoniae and acute chest syndrome in patients with sickle cell disease; Dean D et al.; PURPOSE Few studies address the association of Chlamydia pneumoniae infection with pulmonary disease and outcome in patients with underlying pathology such as sickle cell disease (SCD) . SCD patients are susceptible to the pulmonary disorder known as acute chest syndrome (ACS), where the etiology remains ill defined . The purpose of this study was to analyze the clinical course and outcome of C . pneumoniae-associated ACS among SCD patients as part of the National Acute Chest Syndrome Study . PATIENTS AND METHODS: This was a longitudinal study of SCD patients presenting with ACS to multiple U.S . medical centers . Two hundred ninety-six SCD patients who developed ACS were tested by PCR for C . pneumoniae and by standard techniques for other respiratory pathogens . These infections were evaluated for association with ACS, clinical course, and complications . RESULTS: Forty-one (14%) patients with first episodes of ACS were PCR positive for C . pneumoniae . Compared with other infections, C . pneumoniae-infected patients were older, were more likely to present with chest pain, and had higher hemoglobin levels at diagnosis . Both groups had similar rates of respiratory failure and prolonged hospitalization . Of the 89 patients with single-pathogen infections, 27 (30%) were due to C . pneumoniae, 21% to Mycoplasma pneumoniae, 10% to RSV, 4% to Staphylococcus aureus, and 3% to Streptococcus pneumoniae . CONCLUSIONS: C . pneumoniae was the most prevalent pathogen in this study of ACS and was responsible for significant morbidity . Additional research is required to develop effective treatment guidelines for ACS.

Otol Neurotol, 2003 Jan, 24(1), 113 - 7
Acute otitis media and facial nerve paralysis in adults; Redaelli de Zinis LO et al.; OBJECTIVE: The pathophysiology and treatment of facial nerve paralysis associated with acute otitis media are still under debate . The objective of this study was to review treatment strategies and extent of recovery in adult patients with the aim of defining a standard treatment protocol for this rare pathologic condition . STUDY DESIGN: Retrospective chart review . SETTING: University hospital, tertiary referral center . PATIENTS: Between 1993 and 2000, 11 patients were admitted for facial nerve paralysis secondary to acute otitis media . There were six women and five men without a history of chronic middle ear disease, who ranged in age from 21 to 71 years . Facial palsy was graded with the House-Brackmann scale: four patients had Grade III palsy, six had Grade IV palsy, and one patient had Grade V palsy . Bacteriologic examination of middle ear fluid was performed in four patients Streptococcus pneumoniae was observed in one patient, and the remaining three cultures were negative . INTERVENTIONS: All patients were treated with parenteral ampicillin-sulbactam or a third-generation cephalosporin in conjunction with oral or intravenous corticosteroids, except in a single patient with diabetes mellitus who received antibiotics alone . Myringotomy alone or with ventilation tube application was performed in eight patients . A simple mastoidectomy without facial nerve decompression was used in a patient with sudden impairment to Grade VI paralysis and worsening otitis after an initial improvement . RESULTS: Normal facial function returned in all patients, independently of the grade of the paralysis, the treatment strategy, or the outcome of the middle ear disease . The time of recovery varied from 2 weeks to 3 months, except for one patient who underwent mastoidectomy and in whom normal function returned in 10 months . CONCLUSIONS: The treatment of facial nerve paralysis secondary to otitis media should be as conservative as possible, using antibiotics and corticosteroids . Myringotomy and a ventilation tube should be added when spontaneous perforation of the tympanic membrane is not present . Mastoidectomy should be performed only when it is necessary to treat otitis media . Facial nerve decompression should not be necessary.

Br J Ophthalmol, 2003 Feb, 87(2), 147 - 8
Community treatment with azithromycin for trachoma is not associated with antibiotic resistance in Streptococcus pneumoniae at 1 year; Gaynor BD et al.; AIMS: To determine if macrolide resistant Streptococcus pneumoniae will be a major concern in areas that receive annual mass azithromycin distributions for trachoma . METHODS: A cross sectional survey was conducted of nasopharyngeal S pneumoniae isolates for susceptibility to azithromycin 1 year after administering a single dose of azithromycin to treat trachoma in a village in Nepal . RESULTS: S pneumoniae was isolated from 50 (86%) of 57 nasopharyngeal cultures and no resistance to azithromycin was detected . CONCLUSION: The authors were unable to demonstrate that mass azithromycin therapy for trachoma produced macrolide resistant S pneumoniae that persists until the next scheduled annual treatment.

Antimicrob Agents Chemother, 2003 Feb, 47(2), 824 - 6
Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae isolated in Algiers, Algeria; Ramdani-Bouguessa N et al.; There are few data on antibiotic resistance of Streptococcus pneumoniae in Algeria . Among 309 strains, 34.6% were penicillin G-nonsusceptible S . pneumoniae strains (25.2% were intermediate and 9.4% were resistant) . Serotypes 1, 5, 14, and 6 were the most frequent in invasive child infections . A multicenter study to standardize the national guidelines is needed.

Antimicrob Agents Chemother, 2003 Feb, 47(2), 804 - 8
Molecular epidemiology of penicillin-resistant and ciprofloxacin-resistant Streptococcus pneumoniae in Canada; Nichol KA et al.; Eighty-nine penicillin- and ciprofloxacin-resistant Streptococcus pneumoniae isolates were evaluated by serotyping and pulsed-field gel electrophoresis . Although penicillin-resistant isolates demonstrated considerable homogeneity, resistance to ciprofloxacin did not correlate with a reduction in genotypic variability . These results suggest that, unlike that of penicillin resistance, the spread of S . pneumoniae ciprofloxacin resistance in Canada is currently not attributable to clonal dissemination.

Antimicrob Agents Chemother, 2003 Feb, 47(2), 739 - 46
Influence of macrolide susceptibility on efficacies of clarithromycin and azithromycin against Streptococcus pneumoniae in a murine lung infection model; Hoffman HL et al.; We evaluated the activities of clarithromycin and azithromycin against 19 isolates of Streptococcus pneumoniae using a neutropenic lung infection model . The isolates included five susceptible isolates (clarithromycin and azithromycin MICs, </=0.12 micro g/ml), nine isolates exhibiting low-level, mefA-mediated resistance (clarithromycin and azithromycin MICs, 0.5 to 32 micro g/ml), and five isolates expressing high-level, ermB-mediated macrolide resistance (clarithromycin and azithromycin MICs, >/=64 micro g/ml) . Infected mice were administered either saline (control), clarithromycin (4, 40, or 200 mg/kg of body weight twice daily or 200 mg/kg once daily), or azithromycin (4, 40, or 200 mg/kg once daily or 40 mg/kg twice daily) by oral gavage for 72 h . Mortality was assessed at regular intervals for 10 days, and survival in each group was compared to that of untreated controls . Animals infected with susceptible isolates demonstrated significant improvement in survival compared to the controls following treatment with either agent at doses of >/=40 mg/kg . In contrast, none of the regimens improved the survival of animals infected with isolates exhibiting high-level macrolide resistance . Among mice infected with strains expressing low-level resistance, significant improvement in survival compared to the controls was noted among isolates treated with clarithromycin at 40 (seven of nine isolates) and 200 (nine of nine isolates) mg/kg twice a day and with azithromycin at 40 (one of nine isolates) and 200 (three of nine isolates) mg/kg once a day . Animals infected with isolates of S . pneumoniae exhibiting low-level, mefA-mediated macrolide resistance responded to treatment with clarithromycin at rates similar to those observed among mice infected with fully susceptible isolates.

Antimicrob Agents Chemother, 2003 Feb, 47(2), 704 - 8
Efflux pump Lde is associated with fluoroquinolone resistance in Listeria monocytogenes; Godreuil S et al.; Five Listeria monocytogenes isolates (CLIP 21369, CLIP 73298, CLIP 74811, CLIP 75679, and CLIP 79372) were found to be resistant to fluoroquinolones during the screening for antibiotic resistance of 488 L . monocytogenes isolates from human cases of listeriosis in France . On the basis of a fourfold or greater decrease in the ciprofloxacin MIC in the presence of reserpine, fluoroquinolone resistance was attributed to active efflux of the drugs . The lde gene (Listeria drug efflux; formerly lmo2741) encodes a 12-transmembrane-segment putative efflux pump belonging to the major facilitator superfamily of secondary transporters that displayed 44% identity with PmrA from Streptococcus pneumoniae . Insertional inactivation of the lde gene in CLIP 21369 indicated that the corresponding protein was responsible for fluoroquinolone resistance and was involved in the level of susceptibility to dyes such as ethidium bromide and acridine orange.

Antimicrob Agents Chemother, 2003 Feb, 47(2), 658 - 64
RWJ-54428 (MC-02,479), a new cephalosporin with high affinity for penicillin-binding proteins, including PBP 2a, and stability to staphylococcal beta-lactamases; Malouin F et al.; RWJ-54428 (MC-02,479) is a new cephalosporin active against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) . The potency of this new cephalosporin against MRSA is related to a high affinity for penicillin-binding protein 2a (PBP 2a), as assessed in a competition assay using biotinylated ampicillin as the reporter molecule . RWJ-54428 had high activity against MRSA strains COL and 67-0 (MIC of 1 micro g/ml) and also showed affinity for PBP 2a, with a 50% inhibitory concentration (IC(50)) of 0.7 micro g/ml . RWJ-54428 also displayed excellent affinity for PBP 5 from Enterococcus hirae R40, with an IC(50) of 0.8 micro g/ml and a MIC of 0.5 micro g/ml . The affinity of RWJ-54428 for PBPs of beta-lactam-susceptible S . aureus (MSSA), enterococci (E . hirae), and Streptococcus pneumoniae showed that the good affinity of RWJ-54428 for MRSA PBP 2a and E . hirae PBP 5 does not compromise its binding to susceptible PBPs . RWJ-54428 showed stability to hydrolysis by purified type A beta-lactamase isolated from S . aureus PC1 . In addition, RWJ-54428 displayed low MICs against strains of S . aureus bearing the four classes of staphylococcal beta-lactamases, including beta-lactamase hyperproducers . The frequency of isolation of resistant mutants to RWJ-54428 from MRSA strains was very low . In summary, RWJ-54428 has high affinity to multiple PBPs and is stable to beta-lactamase, properties that may explain our inability to find resistance by standard methods . These data are consistent with its excellent activity against beta-lactam-resistant gram-positive bacteria.

Antimicrob Agents Chemother, 2003 Feb, 47(2), 518 - 23
Suboptimal antibiotic dosage as a risk factor for selection of penicillin-resistant Streptococcus pneumoniae: in vitro kinetic model; Odenholt I et al.; Optimizing pharmacokinetic/pharmacodynamic indices of antibiotics to obtain clinical and microbiological efficacy is essential, but dosing regimens must also be tailored to minimize the risk for emergence of resistance . The aim of the present study was to investigate whether certain concentrations of benzylpenicillin are critical for the selection of resistant subpopulations . A mixed culture of Streptococcus pneumoniae containing ca . 90% susceptible (MIC = 0.031 mg/liter), 9% intermediate (MIC = 0.25 mg/liter), and 1% resistant (MIC = 8 mg/liter) was studied in an in vitro kinetic model . The time that concentrations exceeded the MIC (T>MIC) for the three strains in the culture was varied by different initial concentrations of benzylpenicillin . Samples for viable counts were withdrawn at different times during 24 h and seeded on blood agar plates and on selective antibiotic-containing plates . The T>MIC varied from 46 to 100% for the susceptible strain, from 6 to 100% for the intermediate strain, and from 0 to 48% for the resistant strain . Our study, which may mimic the clinical situation with carriage of a mixed population of S . pneumoniae with different antibiotic susceptibilities, has shown that selection of resistant bacteria may easily occur if dosing regimens are only targeted toward fully susceptible strains.

Antimicrob Agents Chemother, 2003 Feb, 47(2), 489 - 93
Macrolide-resistant Streptococcus pneumoniae and Streptococcus pyogenes in the pediatric population in Germany during 2000-2001; Reinert RR et al.; In a nationwide study in Germany covering 13 clinical microbiology laboratories, a total of 307 Streptococcus pyogenes (mainly pharyngitis) and 333 Streptococcus pneumoniae (respiratory tract infections) strains were collected from outpatients less than 16 years of age . The MICs of penicillin G, amoxicillin, cefotaxime, erythromycin A, clindamycin, levofloxacin, and telithromycin were determined by the microdilution method . In S . pyogenes isolates, resistance rates were as follows: penicillin, 0%; erythromycin A, 13.7%; and levofloxacin, 0% . Telithromycin showed good activity against S . pyogenes isolates (MIC(90) = 0.25 micro g/ml; MIC range, 0.016 to 16 micro g/ml) . Three strains were found to be telithromycin-resistant (MIC >/= 4 micro g/ml) . Erythromycin-resistant strains were characterized for the underlying resistance genotype, with 40.5% having the efflux type mef(A), 38.1% having the erm(A), and 9.5% having the erm(B) genotypes . emm typing of macrolide-resistant S . pyogenes isolates showed emm types 4 (45.2%), 77 (26.2%), and 12 (11.9%) to be predominant . In S . pneumoniae, resistance rates were as follows: penicillin intermediate, 7.5%; penicillin resistant, 0%; erythromycin A, 17.4%; and levofloxacin, 0% . Telithromycin was highly active against pneumococcal isolates (MIC(90) </= 0.016 micro g/ml; range, 0.016 to 0.5 micro g/ml) . The overall resistance profile of streptococcal respiratory tract isolates is still favorable, but macrolide resistance is of growing concern in Germany.

Scand J Immunol, 2003 Jan, 57(1), 45 - 55
Intranasal Cry1Ac protoxin is an effective mucosal and systemic carrier and adjuvant of Streptococcus pneumoniae polysaccharides in mice; Moreno-Fierros L et al.; Streptococcus pneumoniae is a major respiratory pathogen in infants, children and the elderly . Available parenteral anti-pneumococcal vaccines based on type-specific capsular polysaccharides (CPSs) are useful in adults but do not elicit protective immunity in infants and young children . To enhance their immunogenicity, pneumococcal CPSs conjugated to proteins are being developed . Mucosal vaccines may induce mucosal and systemic immune responses, but their development has been hampered by the lack of effective, inexpensive innocuous mucosal adjuvants or immunogenic vaccine carriers . We have demonstrated that the recombinant Cry1Ac protoxin from Bacillus thuringiensis is highly immunogenic and has mucosal and systemic adjuvant effects on proteins coadministered in mice . In this work, we evaluated Cry1Ac as a carrier and adjuvant of S . pneumoniae CPS for the induction of mucosal and systemic antibody responses after intranasal and intraperitoneal immunization in mice . Our results demonstrate that intranasal application of pneumococcal polysaccharides either coadministered or conjugated with Cry1Ac induces higher systemic and mucosal specific antibody responses than those elicited by pneumococcal polysaccharides alone . Adjuvant effects of Cry1Ac on polysaccharides may be appropriate for vaccine design.

Dis Aquat Organ, 2002 Nov 22, 52(2), 129 - 36
Dormancy as a survival strategy of the fish pathogen Streptococcus parauberis in the marine environment; Curras M et al.; The fate of Streptococcus parauberis in seawater and sediment microcosms at different temperatures (6 and 22 degrees C) was investigated by comparing the survival dynamics of 2 strains of this bacterial species, isolated respectively from diseased turbot and cattle . The turbot and the bovine isolate showed similar survival kinetics, remaining culturable for approximately 1 mo in water and 6 mo in sediment . A slight influence of temperature on the stability of the cells was observed, in that the number of culturable cells was about 1 log10 unit higher at 6 than at 22 degrees C . During the starvation period, the metabolic activity of the cells, after suffering a strong reduction during the first 12 d, stabilized at levels ranging from 20 to 40% of the initial values . However, in all the microcosms, the acridine orange (AO) and 4',6-diamidino-2-phenilindole (DAPI) counts remained at about 10(5) cells ml(-1) throughout the experimental period, even when cells became undetectable by standard plate count methods . The addition of fresh medium to microcosms containing nonculturable cells induced the return to culturability of S . parauberis strains . On the basis of these results, it seems that S . parauberis has the ability to enter into a viable but nonculturable (VBNC) state . Dormant cells of the turbot isolate maintained their infectivity and pathogenic potential for fish.

Lin Chuang Er Bi Yan Hou Ke Za Zhi, 2001 Mar, 15(3), 125 - 6
{A report of twice outbreak epidemic of acute tonsillitis and acute pharyngitis}; Jiang X et al.; OBJECTIVE: To discuss the pathogenic factors, prevention and treatment of fulminant epidemic of acute tonsillitis and acute pharyngitis . METHOD: We investigated and analysed the cases of twice fulminant epidemic of acute tonsillitis and acute pharyngitis . RESULT: In the first time, 91 patients among 518 persons were attacted, the sick rate was 17.6% . In the second time, 39 among 295 persons were attacted, the sick rate was 13.2% . The main symptoms were pharyngodynia and fever . Bacterial culture of throat swab of 20 cases of the first time and 17 cases of the second time were carried out . The positive rate of beta-hemolytic streptococcus was 82.5% and 85.3% respectively . CONCLUSION: Environment and individual health condition are important factors in the fulminant epidemic of acute tonsillitis and acute pharyngitis.

Infect Immun, 2003 Feb, 71(2), 948 - 55
Infection by Streptococcus pyogenes induces the receptor activator of NF-kappaB ligand expression in mouse osteoblastic cells; Okahashi N et al.; Group A Streptococcus pyogenes is known to induce nongonococcal septic arthritis in addition to pharyngitis, scarlet fever, and poststreptococcal sequelae . However, little is known about the interaction between S . pyogenes and bone cells . We report here that S . pyogenes strain JRS4 (M6) attached to and invaded mouse primary osteoblasts . Reverse transcription-PCR demonstrated that S . pyogenes infection of osteoblasts stimulated expression of mRNA for the receptor activator of NF-kappaB ligand (RANKL) . Western blot analysis followed by ligand precipitation with the receptor activator of NF-kappaB receptor showed that there was an increase in RANKL protein in infected osteoblasts . Production of interleukin-6 was also stimulated, but no production of interleukin-1beta or tumor necrosis factor alpha was observed . Stimulation of RANKL production was not observed in osteoblasts stimulated with heat-inactivated S . pyogenes, suggesting that an active interaction of S . pyogenes with osteoblasts is essential for this phenomenon . A Western blot analysis performed with antibodies specific for phosphorylated signal transduction proteins demonstrated that S . pyogenes infection induces phosphorylation of p38 mitogen-activated protein kinase . A specific inhibitor of this kinase, SB203580, inhibited RANKL production by infected osteoblasts . These results suggest that infection of osteoblasts by S . pyogenes stimulates RANKL production and may trigger bone destruction in infected bone tissue.

Infect Immun, 2003 Feb, 71(2), 784 - 93
Streptococcus pyogenes glycoprotein-binding strepadhesin activity is mediated by a surface-associated carbohydrate-degrading enzyme, pullulanase; Hytonen J et al.; The interactions between pathogenic bacteria and the host need to be resolved at the molecular level in order to develop novel antiadhesive drugs and vaccines . We have previously identified strepadhesin, a novel glycoprotein-binding activity in Streptococcus pyogenes binding to thyroglobulin, submaxillar mucin, fetuin, and asialofetuin . The activity is known to be regulated by Mga, a regulator of streptococcal virulence factors, and is carried by the surface-associated streptococcal cysteine protease, SpeB . In the present study, we focused on the high strepadhesin activity in an S . pyogenes strain (NZ131rgg) lacking SpeB expression . By extracting surface proteins from the bacteria, a new strepadhesin protein was identified, and mass spectrometric analysis and database search identified it as a putative pullulanase . The gene was cloned, and the recombinant pullulanase (PulA) exhibited pullulanase and starch hydrolyzing activity, as well as strepadhesin activity . Sequencing of the pulA gene revealed an open reading frame with 3,498 bp encoding a protein of 1,165 amino acids with a predicted molecular mass of 129 kDa . PulA exhibited properties typical for a gram-positive surface protein with a putative signal sequence and LPKTGE cell wall anchoring motif and contained the four highly conserved regions common to pullulanases . Mutant bacteria deficient in PulA expression showed diminished strepadhesin activity on bacterial dot blot assay and reduced adherence to thyroglobulin immobilized on microtiter plates . Thus, S . pyogenes strepadhesin activity is carried by a surface-bound pullulanase, which combines glycoprotein-binding and carbohydrate-degrading activities in the same molecule.

Infect Immun, 2003 Feb, 71(2), 754 - 65
Characterization of the conformational epitope of Guy's 13, a monoclonal antibody that prevents Streptococcus mutans colonization in humans; van Dolleweerd CJ et al.; Guy's 13 is a mouse monoclonal antibody which recognizes streptococcal antigen I/II (SA I/II), a major cell surface glycoprotein of Streptococcus mutans . In a number of clinical trials, this antibody has been shown to prevent colonization in the human oral cavity . The aim of this study was to identify the SA I/II epitope recognized by Guy's 13 . The data suggest that the epitope is conformational, delimited by two noncontiguous regions of the antigen: residues 45 to 457, within the N-terminal half of SA I/II, and residues 816 to 983, within the C-terminal half . In fluid-phase immunoassays a strict requirement for the simultaneous presence of both regions was demonstrated for antibody binding . Furthermore, these two regions of SA I/II were shown to have the ability to interact with each other in the absence of Guy's 13 antibody, suggesting that the normal conformation of SA I/II might be determined by the interaction of these two regions.

Infect Immun, 2003 Feb, 71(2), 676 - 81
Roles of sortase in surface expression of the major protein adhesin P1, saliva-induced aggregation and adherence, and cariogenicity of Streptococcus mutans; Lee SF et al.; Sortase is a newly discovered transpeptidase that covalently links LPXTGX-containing surface proteins to the gram-positive bacterial cell wall . In this study, the sortase gene (srtA) was isolated from Streptococcus mutans NG8 by PCR . The gene encoded a 246-amino-acid protein, including a 40-amino-acid signal peptide . The srtA gene was insertionally inactivated by a tetracycline resistance cassette . P1, a major surface protein adhesin previously shown to anchor to the peptidoglycan by the LPXTGX motif, was secreted into the culture medium by the srtA mutant . In contrast, the wild-type P1 remained cell wall associated . Complementation of the mutant with srtA restored the P1 surface expression phenotype . P1 produced by the mutant, but not that produced by the wild type and the srtA-complemented mutant, was recognized by an antibody raised against the hydrophobic domain and charged tail C terminal to the LPXTGX motif . These results suggest that the failure to anchor P1 to the cell wall is due to the lack of cleavage of P1 at the LPXTGX motif . The srtA mutant was markedly less hydrophobic than the wild type and the complemented mutant . The srtA mutant failed to aggregate in the presence of saliva or salivary agglutinin and adhered poorly to saliva- or salivary agglutinin-coated hydroxylapatite . In rats, the srtA mutant colonized the teeth poorly when sucrose was absent . When sucrose was present, the srtA mutant colonized the teeth but less effectively and induced significantly less caries (P < 0.05) than the wild-type strain . In conclusion, the sortase enzyme in S . mutans is responsible for anchoring P1 to the cell surface and plays a role in modulating the surface properties and cariogenicity of S . mutans.

Age Ageing, 2003 Jan, 32(1), 95 - 101
Infectious aetiologies in elderly patients hospitalised with non-pneumonic lower respiratory tract infection; Lieberman D et al.; OBJECTIVE: to identify the infectious aetiologies of non-pneumonic lower respiratory tract infections in hospitalised elderly patients, and to characterise the patients in terms of demographic, clinical and therapeutic variables . DESIGN:a prospective, non-interventional, purely serologically based diagnostic study . SETTING: a tertiary university hospital in southern Israel . SUBJECTS:133 elderly patients hospitalised for non-pneumonic lower respiratory tract infections . METHODS: paired sera were obtained for each of the hospitalisations and were tested using immunofluorescence or enzyme immunoassay methods to identify 13 different pathogens . Only significant changes in antibody titers or levels between the paired sera were considered diagnostic . RESULTS: at least one infectious aetiology was identified in 77 patients (58%) . At least one of seven viral aetiologies was identified in 52 patients (39%) . A bacterial aetiology was identified in 27 patients (20%) including Streptococcus pneumoniae in 24 (18%) . An atypical bacterium was found in 27 patients (20%) including Mycoplasma pneumoniae in 15 (11%) and Legionella spp . in nine (7%) . More than one aetiology was found in 23 patients (17%) . One hundred and twenty nine patients (96%) suffered from serious chronic co-morbidity . One hundred and twenty one patients received antibiotics during their hospitalisation, 106 (80%) with a beta-lactam and 42 (31%) with another antibiotic . CONCLUSIONS: non-pneumonic lower respiratory tract infection is caused in hospitalised elderly patients by a broad spectrum of aetiological agents, primarily respiratory viruses with a significant, though lesser, prevalence of classical and atypical bacteria . Despite this distribution of aetiologies, most patients are treated with beta-lactam antibiotics . The indication for antibiotic therapy in these patients and the choice of antibiotic preparation should be addressed in further studies.

South Med J, 2002 Nov, 95(11), 1293 - 6
Pneumococcal susceptibility to meropenem in a mid-south children's hospital; Buckingham SC et al.; BACKGROUND: We investigated pneumococcal susceptibility to meropenem in isolates from a tertiary children's hospital where pneumococci are commonly resistant to penicillin and cefotaxime . METHODS: From July 1998 to August 1999, meropenem susceptibilities were determined by E-test for all Streptococcus pneumoniae isolates from blood or cerebrospinal fluid and for penicillin-nonsusceptible pneumococcal isolates from other sites . RESULTS: Isolates that were penicillin-susceptible or penicillin-intermediate were all susceptible to meropenem . Of 29 penicillin-resistant isolates, 27 were nonsusceptible to meropenem (13 intermediate, 14 resistant) . Cefotaxime-susceptible isolates were all susceptible to meropenem . Of 11 cefotaxime-intermediate isolates, 10 were nonsusceptible to meropenem (9 intermediate, 1 resistant) . Of 20 cefotaxime-resistant isolates, 17 were nonsusceptible to meropenem (4 intermediate, 13 resistant) . CONCLUSIONS: Meropenem resistance is common among pneumococci with decreased susceptibility to penicillin or cefotaxime . The role of this agent in the treatment of invasive infections caused by pneumococci that are resistant to penicillin and cefotaxime may be limited.

Hua Xi Kou Qiang Yi Xue Za Zhi, 2001 Aug, 19(4), 249 - 52
{Construction of eukaryotic expression plasmid pcDNA3-gtfB expressing glucosyltransferase B of Streptococcus mutans}; Yang J et al.; OBJECTIVE: Glucosyltransferase (GTF) of Streptococcus mutans is considered as a cariogenic virulence factor due to its ability to synthesize glucan, which facilitate sucrose-depended adherence and cell-to-cell accumulation of bacteria . In this study, gtfB, the target gene fragment which encodes multiple catalytic sites and antigen epitopes of GTF, was recombined into eukaryotic expression vector pcDNA3 . The feasibility of the recombination plasmid pcDNA3-gtfB used as gene vaccine will be investigated in further study . METHODS: The target gene fragment gtfB (904-4578 bp) was obtained by standard PCR amplification while genome DNA of streptococcus mutans GS-5 was used as template . Then the PCR products were extracted and purified from low-melting temperature agarose . The gtfB and plasmid pcDNA3 were cut by Kpn I, Xho I, and the digested products were extracted and purified again for recombination . The purified gtfB and plasmid pcDNA3 were recombined by T4 DNA ligase, ligation products were transformed into competent cell, Escherichia coli JM109 . Transformed colonies were screened by Ampr LB plate, then recombined plasmids were isolated and identified by restricted endonuclease cutting and Sanger dideoxy DNA sequencing . RESULTS: Identified by agarose gel electrophoresis, the target gene-gtfB obtained PCR amplification had the same molecular size (36 kb) as predicted . It was indicated that recombined plasmids contained inserted gtfB gene fragment by restricted endonuclease cut analysis, the sequencing data also indicated that inserted gtfB gene had correct DNA sequence and orientation according to DNA sequence of Streptococcus mutans GS-5 (gene bank M17361) . CONCLUSION: Inserted gene-gtfB of recombined plasmid pcDNA3-gtfB encoded multiple catalytic sites and epitopes . It was proved that these epitopes had high immune antigenicity and that antiserum could significantly inhibit the synthesis of water-insoluble glucans and water-soluble glucan . In vitro adherence experiment also indicated that it could inhibit streptococcus mutans adherence to saliva-coated hydroxyapatite . Vector pcDNA3 was high expressing eukaryotic vector, and could stimulate antigen-representing cell . It was suggested that recombined plasmid pcDNA3-gtfB had high immune antigenicity and immune responsiveness, and this supported its use as gene vaccine candidates in the development of anti-caries vaccines.

Hua Xi Kou Qiang Yi Xue Za Zhi, 2001 Aug, 19(4), 219 - 21
{The isolation and identification of pathogenic bacteria from rampant caries in children}; Liu Y et al.; OBJECTIVE: In order to prevent rampant caries in children, the predominant pathogenic bacteria of rampant caries in children were defined . METHODS: The pathogenic bacteria of rampant caries were isolated and identified in 30 children with rampant caries, aged from 2 to 5 years old . Samples were collected from the caries of labial surfaces of maxillary anterior deciduous teeth, including caries lesions and caries-free smooth enamel surfaces . Plaque were obtained from the cervical third areas of the maxillary labial anterior deciduous tooth surfaces in children without rampant caries and caries-free children and served as controls respectively . The isolates were identified by colony morphology, biochemical tests and DNA base contents (mol percent G + C) . RESULTS: The prevalence of Streptococcus mutans (S . mutans) and Streptococcus sobrinus (S . sobrinus) in the plaque of caries lesions and the proportions of S . mutans and S . sobrinus in the plaque of 2 sampling sites of children with rampant caries were all significantly higher than those of children without rampant caries and caries-free children (P < 0.05) . CONCLUSION: S . mutans and S . sobrinus are predominant pathogenic bacteria in rampant caries in children.

Hua Xi Kou Qiang Yi Xue Za Zhi, 2000 Jun, 18(3), 163 - 4, 180
{Effect of calcium on adherence of Streptococcus mutans MT6R(serotype c) surface protein P1}; Huang D et al.; OBJECTIVE: To study effects of calcium on the adherence of Streptococcus mutans MT6R(serotype c) surface protein P1 to saliva-coated hydroxyapatite(S-HA) . METHODS: The surface protein P1 of Streptococcus mutans MT6R was purified by PAGE and labeled with 131I(131I-P1) . The adherence amount of 131I-P1 to S-HA in different calcium concentration liquid was measured . RESULTS: The amount of 131I-P1 adherence to S-HA in 0, 0.1, 0.25, 0.5, 1.0, 1.5, 2.0 mmol/L, and calcium was 7175 + 183, 7516 + 192, 8850 + 215, 9335 + 204, 10087 + 228, 10179 + 224 and 10200 + 317 cpm, respectively(P < 0.01) . The calcium concentration from 0 to 1.0 mmol/L, the amount of 131I-P1 adherence was increased statistically(P < 0.05), calcium concentration from 1.0 mmol/L to 2.0 mmol/L, the amount of 131I-P1 adherence was increased unstatistically(P > 0.05) . CONCLUSION: Calcium promoted the adherence of surface protein P1 to the S-HA . This result suggested that calcium was involved in the adherence of Streptococcus mutans MT6R (serotype c) surface protein P1.

Hua Xi Kou Qiang Yi Xue Za Zhi, 2000 Oct, 18(5), 336 - 9
{The effects of tea polyphenols on the adherence of cariogenic bacterium to the salivary acquired pellicle in vitro}; Xiao Y et al.; OBJECTIVE: It has been proved that tea polyphenols (TP) can inhibit the sucrose-dependent adherence of oral cariogenic bacterium to the tooth surface . This study is carried on to investigate the effects of tea polyphenols on the preliminary adherence of main cariogenic bacterium to salivary acquired pellicle and reveal the anticarious mechanisms of tea polyphenols further . METHODS: The hydroxyapatites were coated by saliva to form S-HA, an in-vitro model of experimental pellicle . Streptococcus mutans 3a3 and Actinomyces viscosus ATCC 19246 were chosen as the main cariogenic bacterium, and the microorganisms were radiolabelled by growing them in TPY culture medium supplemented with 3H-thymidine . Tea polyphenols solution was prepared, the concentrations of which were 0.5, 1.0, 2.0 and 4.0 mg/ml respectively . Two parts of inhibited adherence tests were done with TP-treated S-HA or TP-treated bacterium . In the first one, S-HA was immerged into the TP solution of different concentrations for 1 h before the attachment of bacterium . In the other, the bacterium were mixed with the TP solution for 1 h and then centrifuged and washed before bound to S-HA . The whole process was carried on in KCl buffer solution . The number of 3H-thymidine-labelled bacterium which attached to S-HA were determined by scintillation counting . RESULTS: In both the two parts of this study, tea polyphenols solution, the concentrations of which were changed from 1.0 to 4.0 mg/ml, could decrease the number of S . mutans 3a3 and A . viscosus ATCC 19246, and the inhibition rates rose with the increase of the concentrations of TP solution . But the inhibitory effects of 0.5 mg/ml TP solution were inconsistent in different tests . The results showed that 1.0-4.0 mg/ml TP solution could inhibit the attachments of S . mutans and A . viscosus to S-HA effectively . The inhibitory functions of tea polyphenols were so obvious that in some experiments, while the concentrations of TP solution were changed from 2.0 to 4.0 mg/ml, the number of 3H-thymidine-labelled bacterium which attached to S-HA was even less than that of the same bacterium which attached to naked HA . CONCLUSION: Tea polyphenols can inhibit the preliminary adherence of Streptococcus mutans and Actinomyces viscosus to S-HA effectively . TP may prevent enamel from caries by decreasing the adherence of main cariogenic bacterium to salivary acquired pellicle.

Hua Xi Kou Qiang Yi Xue Za Zhi, 2000 Oct, 18(5), 332 - 5
{The disinfection efficiency comparison of different treatments on dental impression and gypsum casts}; Zhao H et al.; OBJECTIVE: In this study, the disinfecting efficiency of five disinfecting methods to three bacterial: Staphylococcus epidermidis, Streptococcus sanguis and Bacillus subtilis were evaluated . METHODS: Germ free impressions and gypsum casts were divided into three teams contained 16 impressions and 5 gypsum casts for each one . Each team was smeared with each one of the three bacterial solutions . Then four disinfecting methods were administrated on these impressions separately, 2% glutaraldehyde immersion, 2% glutaraldehyde spray, 5% Eric immersion, 5% Eric spray . And ozone treatment was administrated on gypsum casts . Control teams were set up . After the treatment the impressions and gypsum casts were sampled at standard sites . The colonies were counted after culture and were used to deduce the germicidal ratio as the standard of disinfecting efficiency . RESULTS: There was no difference between the efficiencies of five disinfecting methods for Streptococcus sanguis and Staphylococcus epidermidis . But for B . subtilis, the immersion methods have the highest efficiency among the methods and the ozone treatment has the least efficiency . CONCLUSION: 2% glutaraldehyde immersion, spray, 5% Eric immersion, spray are all effective disinfecting methods for impressions and ozone treatment is an effective method in disinfecting the gypsum casts.

J Tongji Med Univ, 2001, 21(4), 269 - 72
Construction and in vitro expression of Streptococcus mutans surface protein encoding DNA vaccine; Peng Z et al.; DNA vaccine plasmids were constructed that encoded two highly-conservative regions of a surface protein, PAc, from the human major cariogenic bacterium, Streptococcus mutans . Antigen expression was evaluated in vitro by immunohistochemical analysis of human endothelial cells following cationic liposome-mediated transient transfection with recombinant plasmid . The results of this study provided a basis for further testing of these recombinant plasmids in primates and for efficacy testing of dental caries DNA vaccines in human volunteers in future.

Hua Xi Kou Qiang Yi Xue Za Zhi, 2001 Oct, 19(5), 312 - 4
{Effects of para-aminobenzoic acid (PABA) on growth of Streptococcus mutans}; Guo B et al.; OBJECTIVE: The aim of this study is to examine effects of para-aminobenzoic acid (PABA) on the growth of Streptococcus mutans (S . mutans) . METHODS: Different concentrations of PABA (10(-10)-10(-3) g/L) were separately transferred to modified Carlsson medium . S . mutans (ATCC 25175) grew in modified Carlsson medium with different concentrations of PABA . All cultures were incubated at 37 degrees C anaerobically in an atmosphere of 80% of nitrogen (v/v), 10% of hydrogen (v/v) and 10% of carbon dioxide (v/v) for 48 hours . The absorbance values of S . mutans were measured by using a spectrometer (UV-1601) . The colony forming units (CFU) were obtained by growing S . mutans in media with different concentrations of PABA (10(-10)-10(-3) g/L) . RESULTS: Different concentrations of PABA had different stimulating effects on the growth of S . mutans (P < 0.05) . But this kind of stimulating effects declined when the concentration of PABA was 10(-3) g/L . CONCLUSION: This experiment indicates PABA has stimulating effects on the growth of S . mutans, and PABA can promote growth of S . mutans.

Hua Xi Kou Qiang Yi Xue Za Zhi, 2000 Dec, 18(6), 419 - 21
{Evaluation of cariogenic potential of Streptococcus mutans isolated from caries-free and -active persons: abilities to synthesize water-soluble and -insoluble glucans}; Huang X et al.; OBJECTIVE: In this study, authors investigated abilities of Streptococcus mutans (serotype c) strains to synthesize water-soluble and water-insoluble glucans . METHODS: Streptococcus mutans strains were isolated from people with different carious experiences, which were divided into two groups: caries-free (DMFS = 0) group including 19 persons and caries-active group(DMFS > or = 6) including 40 persons . Totally 105 genotypes of Streptococcus mutans strains were obtained, including 22 strains from the caries-free group and 83 strains from the caries-active group . The differences of abilities to synthesize water-soluble and water-insoluble glucans between these two groups were compared in order to find the correlationship between the synthesis of glucans and caries experience . Then, Streptococcus mutans were cultured in TPY liquid medium containing 1% sucrose in an anaerobic incubator at 37 degrees C for 24 hours . Glucans synthesized by Streptococcus mutans was qualified by using infrared spectrophotometry . The amounts of water-soluble and water-insoluble glucans were measured by using the anthron method . RESULTS: According to the same absorption tops position analysed by infrared spectrophotometry, glucans samples were certified . The amounts of glucans synthesized by Streptococcus mutans strains were different between strains of different genotypes even isolated from the same person . Mostly, the amount of water-insoluble glucans was higher than that of water-soluble glucans between different genotype Streptococcus mutans strains . The oral environments of patients in the caries-active group harbored more Streptococcus mutans strains with higher water-soluble glucans producing ability than those of the caries-free group did (P < 0.05), and patients of the caries-active group also harbored more Streptococcus mutans strains with higher water-insoluble glucans producing ability than those of the caries-free group did(P < 0.01) . CONCLUSION: 1 . Glucosyltranferases of different genotype strains are different in glucans production, and different genotype strains relate to different cariogenic abilities . 2 . Glucans was one of cariogenic factors, and water-insoluble glucans was more important than water-soluble glucans in cariogenic ability of Streptococcus mutans . 3 . The differences in glucans production of isolated strains might relate to differences in carious experiences.

Hua Xi Kou Qiang Yi Xue Za Zhi, 2000 Dec, 18(6), 408 - 11
{Construction of two eukaryotic expression plasmids pcDNA3/pacA and pcDNA3/pacP expressing surface protein antigen of Streptococcus mutans}; Guo L et al.; OBJECTIVE: Two gene vaccines which encoded amino terminal and intermediate region in the PAc protein were constructed and the feasibility and safety was investigated, in order to obtain a highly effective and secure anticarious way by immunization . METHODS: The target gene fragments pac-A and pac-P encoded amino terminal and intermediate region of surface protein antigen from Streptococcus mutans were obtained by PCR amplification respectively . Amplification products were isolated by using low melting-temperature agarose and recoveried from the gel . Then the two fragments were digested by Kpn I and Xho I, and ligated to the Kpn I-Xho I-digested eukaryotic shuttle expression vector pcDNA3 to create reconstructed plasmids pcDNA3/pacA and pcDNA3/pacP respectively . The ligated DNAs were transformed into Escherichia coli XL1-Blue . Transformed colonies carrying eukaryotic expression plasmid either pcDNA3/pacA or pcDNA3/pacP were screened by colony hybridization in situ . Then the reconstructed plasmids were isolated and identified by restricted endonuclease digestions, Southern hybridization and DNA sequencing . RESULTS: 1 . Two DNA fragments pac-A and pac-P of the predicted size 1.3 kb and 1.2 kb were obtained by PCR amplified . 2 . Eukaryotic expression plasmids pcDNA3/pacA and pcDNA3/pacP had been reconstructed correctly . 3 . The sequencing data also indicated that the pcDNA3 construct contained the correct sequence and orientation of the two target genes . CONCLUSION: These two plasmids may act as gene vaccines for further study.

Hua Xi Kou Qiang Yi Xue Za Zhi, 2001 Apr, 19(2), 89 - 92
{A study on transmission of pathogenic bacteria of rampant caries from mothers to children}; Liu Y et al.; OBJECTIVE: In order to prevent rampant caries in children, the transmission from mothers to children of pathogenic bacteria of rampant caries will be investigated in this study . METHODS: By using fingerprint technique, the genetic diversities of Streptococcus mutans(S . mutans) were examined respectively in 10 children with rampant caries, 10 children without rampant caries S . mutans, 10 2-year-old caries-free children, and their mothers . The levels of S . mutans in saliva of mothers were also examined . For fingerprinting, chromosomal DNA of isolates obtained from plaques of these children and from saliva of their mothers were digested with restriction endonuclease HindIII and examined by electrophoresis on 0.7% agarose gel . DNA fingerprints were obtained and analyzed for genotypic similarities . RESULTS: The DNA fingerprint patterns showed that the proportion of children whose genotypes of S . mutans matched their mothers in the children with rampant caries was 70%, which is similar to that in the children without rampant caries and the caries-free children (60% respectively) . The number of distinct genotypes of S . mutans harbored in children with rampant caries was, on average, greater than the number of genotypes present in children without rampant caries and caries-free children (1.7, 1.2 and 1.1 respectively, P < 0.05) . Mothers of children with rampant caries had similar levels of S . mutans in saliva as those mothers of children without rampant caries and caries-free children . However, mothers of children with rampant caries had significantly higher DMFT scores and higher levels of Streptococcus sobrinus (S . sobrinus) in saliva than the mothers of caries-free children did . CONCLUSION: In all child groups, mothers were probably the main source of infection with S . mutans . Rampant caries in children is associated with DMFT scores and levels of S . sobrinus in saliva of mothers . In the initiation of rampant caries experienced by a child, the transmission of pathogenic bacteria from mothers to children may be the main source.

Hua Xi Kou Qiang Yi Xue Za Zhi, 2001 Apr, 19(2), 71 - 3
{Effects of immune bovine whey on sucrose-dependent adherence of Streptococcus mutans}; Fan M et al.; OBJECTIVE: The aim of this experiment is to explore the possible anti-carious mechanisms of immune bovine whey . METHODS: The immune milk was collected from cows immunized with cell associated glucosyltransferase(GFT) over-expression strain B-29-33 of Streptococcus mutans(S . mutans) MT8148 . The control milk was obtained from non-immunized cows . The immune and control bovine whey were prepared by removing fat and casein . The effects of two kinds of bovine whey on sucrose-dependent adherence of S . mutans MT8148 were examined by using TTY media with five different volumes of the immune and the control milk, 100, 300, 500, 700 and 900 microliters respectively . The adherent rates were determined by reading the optical density . The adherent morphology was observed by using a scanning electron microscope(SEM) . RESULTS: There was no significant difference in adherence of S . mutans MT8148 cells to the smooth glass surface among five doses with those of the control whey . The immune bovine whey inhibited the adherence of S . mutans . The adherent percentage was 84.37% at 100 microliters and decreased by 58.59% at 900 microliters . The inhibition was does-dependent . The difference of adherent morphology between the immune and control whey was noticeable at 900 microliters . The SEM revealed that cells of S . mutans MT8148 with the control whey were covered by large quantities of gelatinous material, but cells with the immune whey were clearly distinguished . CONCLUSION: The immune whey has inhibitory potential against the sucrose-dependent adherence of S . mutans.

Hua Xi Kou Qiang Yi Xue Za Zhi, 1999 Nov, 17(4), 364 - 6
{Construction of Streptococcus mutans surface protein antigen eukaryotic expression vector pcDNA3-PAc . II . Testified efficiency of repeated using glass fiber chromatographic column}; Liu J et al.; OBJECTIVE: To explore one method getting highly purified plasmid DNA and costing low . METHODS: According to principle of extraction and purification plasmid DNA of glass fiber chromatographic column, its operation sequence was improved so that disposable glass fiber chromatographic column could be used repeatedly . The concentration and purity of plasmid DNA obtained by 12 times repeated using glass fiber chromatographic column were determined by spectrophotometry . Moreover, Those plasmid DNA obtained were tested by restriction enzyme and agarose gel electrophoresis, Ligation in vitro and transformation test . RESULTS: 12 times repeated use of glass fiber chromatographic column made no significant difference to the concentration and purity of obtained plasmid DNA (P < 0.05), and plasmid DNA was completely digested by restriction enzyme . The digested fragments were well ligated together by the action of T4 DNA Ligase in ATP ligating buffer in vitro and ligated DNA was well transformed into E . coli . CONCLUSION: Repeated use glass fiber chromatographic column can obtain a lot of highly purified plasmid DNA and cost is low . Digestion, ligation and transformation of those plasmid DNA are not affected . The results may be significant in molecular cloning and study of gene vaccination.

Hua Xi Kou Qiang Yi Xue Za Zhi, 1999 Nov, 17(4), 361 - 3
{Construction of Streptococcus mutans surface protein antigen eukaryotic expression vector pcDNA3-PAc . I . Extraction and purification of plasmid DNA pPC41 and pcDNA3}; Liu J et al.; OBJECTIVE: To Extract and purify plasmid DNA pPC41 and pcDNA3 . METHODS: Bacteria were collected and lyzed by the alkaline lysis method . The plasmid pPC41 carrying structural gene pac and clone expression vector pcDNA3 were extracted and purified from E . coli clone by the polyethylene glycol precipitating method, the electroelution into dialysis bags method, the low melting-temperature agarose gel and glass fiber column chromatography . The concentration, purity and molecular weight were determined by spectrophotometry, restriction enzyme and agarose gel electrophoresis . RESULTS: The concentration of plasmid DNA of this experiment in general was 0.12-0.24 g/L, and A260/A280 of the polyethylene glycol precipitating method, the electroelution into dialysis bags method, the low metling-temperature agrose gel and glass fiber column chromatography were respectively 1.9, 2.2, 2.2 and 2.6 . Molecular weight of pPC41 and pcDNA3 was respectively 10.6 kb and 5.4 kb . CONCLUSION: The four methods can obtain pure plasmid DNA . Purity of plasmid DNA obtained by glass fiber column chromatography method is the highest in the four methods . Glass fiber column chromatography is one of the effective methods getting highly purified plasmid DNA.

Hua Xi Kou Qiang Yi Xue Za Zhi, 1999 Nov, 17(4), 314 - 7
{Separation and selection of salivary adhesion receptors of Streptococcus mutans to tooth surface}; Zhan L et al.; OBJECTIVE: To select and purify salivary receptors of Streptococcus mutans from experimental salivary acquired pellicle . METHODS: Experimental salivary acquired pellicle (SAP) was performed by coating hydroxyapatite (HA) with whole saliva . Then SAP was washed from HA by 1 mol/L NaCl and 0.5 mol/L phosphate buffer sequentially . The proteins were further separated by chromatography of Sephadex G75 and DEAE-Sephadex A25 . Receptors of Streptococcus mutans were selected by bacterial adhesion test and competitive inhibition adhesion test . Identification was performed by PAGE, SDS-PAGE, IP-PAGE and detection of amylase activity and inmunodifusion test . RESULTS: IgA degraded fragments, a protein of 13 kD and amylases were the receptors of S . mutans . The first two only promote the adhesion but the amylases can both promote and inhibit S . mutans adhesion . CONCLUSION: The adhesion of S . mutans to tooth surface is a result of interaction between adhesins of S . mutans and multiple salivary receptors.

Hua Xi Kou Qiang Yi Xue Za Zhi, 1999 Nov, 17(4), 310 - 3
{Investigation on interaction between Streptococcus sanguis and Porphyromonas gingivalis in specific pathogen-free rats}; Zhou C et al.; OBJECTIVE: To examine whether endogenous S . sanguis could prevent, or reduce the colonization of the virulent P . gingivalis strain . METHODS: First, 10 specific pathogen-free Wistar rats were divided into 2 groups . Doxycycline was administered in the drinking water for 7 days . Successful implantation of the endogenous strain of S . sanguis, isolated from one of the rats before doxycycline administration, and P . gingivalis 381 within 14 days of observation were demonstrated in the rats of each group respectively . Then, 30 SPF rats were divided into 6 groups . Doxycycline was administered in the drinking water for 7 days to all the rats . Afterwards, the rats in group A and B were inoculated orally once a day for 5 days with P . gingivalis, the rats in group C and E were inoculated orally once a day for 5 days with S . sanguis . Then, the rats in group A were inoculated for 5 days with S . sanguis, and rats in group C and D were inoculated for 5 days with P . gingivalis . The rats in group F served as negative control . After inoculation, the levels of S . sanguis and P . gingivalis in the mouths of the rats were determined after 12, 24, 36 hours, 7 days and 14 days . RESULTS: Both pre-colonization of S . sanguis and superinfection with S . sanguis did reduce the level of P . gingivalis in experimental rats . However, the reduction only maintained quite short time, about 36 hours . It was not caused by the decreased level of S . sanguis after 36 hours because the level of S . sanguis kept stable during the observation period of 14 days . CONCLUSION: That S . sanguis function as the effector strain requires the successful implantation of S . sanguis as well as S . sanguis producing antagonistic action efficiently in vivo.

Hua Xi Kou Qiang Yi Xue Za Zhi, 1999 Feb, 17(1), 14 - 6
{Cloning and sequencing of variable region gene of heavy chain of monoclonal antibody against SA I/II of Streptococcus mutans}; Wen L et al.; OBJECTIVE: To clone and sequence a immunoglobulin variable region of heavy chain (VH) from a mouse hybridoma 2B12F6, which produce monoclonal antibody against SA I/II of Streptococcus mutans . METHODS: The immunoglobulin variable region gene of heavy chain of 2B12F6 was amplified and cloned into pUC18 by using PCR technique and gene engineering technique, and then the gene sequence was analyzed by Sanger's method . RESULTS: The VH gene segment was 360 base pairs in length and coded 118 amino acids, and the homology of framework of VH gene and mouse VH gene published was 70%, which accorded with the feature of mouse VH gene . CONCLUSION: The VH gene gained from 2B12F6 could provide the possibility of construction of gene engineering antibody against SA I/II of Streptococcus mutans.

Hua Xi Kou Qiang Yi Xue Za Zhi, 1999 Feb, 17(1), 11 - 3
{Partial gene clone and nif gene homologous sequence analysis of Streptococcus sanguis}; Pan Y et al.; OBJECTIVE: To analyze the sequence of Streptococcus sanguis chromosome which contains one DNA fragment of 800 base pairs (bp) and discuss Streptococcus sanguis biological features of heredity . METHODS: Streptococcus DNA of 800-bp genetic fragment was cloned and analyzed by using eukaryotic expression vector . RESULTS: By Genbank database, it showed that the 800-bp genetic sequence was highly homologous with other bacterial nifS and nifU gene, and the highest homologous score was 114 . CONCLUSION: This nif gene of ATCC 10556 strain may correlate with nutrient metabolism and peroxide hydrogen release of Streptococcus sanguis.

Hua Xi Kou Qiang Yi Xue Za Zhi, 1999 Aug, 17(3), 227 - 9, 232
{Isolation, purification and antibacterial activities of salivary histidine-rich polypeptides}; Luo H et al.; OBJECTIVE: To isolate and purify salivary histidine-rich-polypeptides (HRPs) and observe their antibacterial activities . METHODS: By using of preparative acid urea polyacrylamide gel electrophoresis (AU-PAGE), three major HRPs(HRP-1, HRP-3 and HRP-5) were purified from parotid saliva collected from healthy adults . Their antibacterial activities were tested in the ultrasensitive antibacterial assay, named radial diffusion assay . RESULTS: Each fraction of the three purified HRPs appeared as a single protein zone both in AU-PAGE and Tricine-SDS-PAGE . Their molecular weights are 3-5 kD as determined by Tricine-SDS-PAGE . All the three major HRPs showed potent bactericidal effects on Streptococcus mutans MT6R and Staphylococcus aureas ATCC25923 . As to Escherichia coli ML-35P and Pseudomonas aeruginosa ATCC27853, HRP-3 and HRP-5 also demonstrated significant antibacterial activities, whereas HRP-1 did not show any inhibitory effects on the viability of them . CONCLUSION: The above results suggested that the method of preparative AU-PAGE we used in this study has the benefits of high resolution, simple manipulation and perfect results of purification . HRPs are important components to prevent oral tissue from bacterial infections, therefore play a potent role in the maintenance of the oral health.

Hua Xi Kou Qiang Yi Xue Za Zhi, 1999 Aug, 17(3), 221 - 3
{Effects of monoclonal antibody against the major cell surface protein on salivary agglutinin mediated aggregation of Streptococcus sobrinus}; Zhang P et al.; OBJECTIVE: To investigate the effects of monoclonal antibody on salivary agglutinin-mediated aggregation of Streptococcus sobrinus in vitro . METHODS: Bacterial aggregation inhibition was measured under OD650 at 10 minutes intervals for 1 hour . RESULTS: It showed that the McAb ZS2/286 raised against the PAg of S . sobrinus 6715 could inhibit the aggregation by some degree, but the effect was not significant . CONCLUSION: The McAb ZS2/286 might not bind directly to the functionally important region of PAg related to aggregation.

Clin Infect Dis, 2003 Feb 1, 36(3), 319 - 27 Epub 2003 Jan 13.
Pneumococcal septic arthritis: review of 190 cases; Ross JJ et al.; This article reports 13 cases of pneumococcal septic arthritis and reviews another 177 cases reported since 1965 . Of 2407 cases of septic arthritis from large series, 156 (6%) were caused by Streptococcus pneumoniae . Mortality was 19% among adults and 0% among children . Pneumococcal bacteremia was the strongest predictor of mortality . At least 1 knee was involved in 56% of adults . Polyarticular disease (36%) and bacteremia (72%) were more common among adults with septic arthritis caused by S . pneumoniae than among adults with other causative organisms . Only 50% of adults with pneumococcal septic arthritis had another focus of pneumococcal infection, such as pneumonia . Functional outcomes were good in 95% of patients . Uncomplicated pneumococcal septic arthritis can be managed with arthrocentesis and 4 weeks of antibiotic therapy; most cases of pneumococcal prosthetic joint infection can be managed without prosthesis removal . A fatal case of septic arthritis caused by a beta-lactam-resistant strain of S . pneumoniae is also presented.

Heart Surg Forum, 2002, 5(3), 298 - 9
Mitral valve aneurysm associated with aortic valve endocarditis and regurgitation; Raval AN et al.; Mitral valve aneurysms are rare complications occurring most commonly in association with aortic valve infective endocarditis . {Decroly 1989, Chua 1990, Northridge 1991, Karalis 1992, Roguin 1996, Mollod 1997, Vilacosta 1997, Cai 1999, Vilacosta 1999, Teskey 1999, Chan 2000, Goh 2000, Marcos- Alberca 2000} While the mechanism of the development of this lesion is unclear, complications such as perforation can occur and lead to significant mitral regurgitation . {Decroly 1989, Karalis 1992, Teskey 1999, Vilacosta 1999}; The case of a 69-year-old male with Streptococcus Sanguis aortic valve endocarditis and associated anterior mitral leaflet aneurysm is presented . Following surgery, tissue pathology of the excised lesion revealed myxomatous degeneration and no active endocarditis or inflammatory cells . This may add support to the hypothesis that physical stress due to severe aortic insufficiency and structural weakening, without infection of the anterior mitral leaflet, can lead to the development of this lesion.

Hua Xi Yi Ke Da Xue Xue Bao, 2001 Sep, 32(3), 348 - 9, 368
{Effect of para-aminobenzoic acid on the adhesion of Streptococcus mutans}; Guo B et al.; OBJECTIVE: To investigate the effects of Para-aminobenzoic acid (PABA) on the adhesion of Streptococcus mutans to saliva-coated hydroxyapatite (S-HA) . METHODS: The adhesion model in vitro established by Gibbons was adopted in this study to quantify adsorptive cells through {3H} thymidine labelling . RESULTS: PABA solution over a range of concentration from 10(-9) to 10(-3) g/L could inhibit the attachment of S . mutans to S-HA effectively, and the inhibition declined when the concentration of PABA solution was 10(-3) g/L . CONCLUSION: PABA can inhibit the adherence of Streptococcus mutans to S-HA effectively.

Tunis Med, 2002 Jun, 80(6), 329 - 33
{Epidemiology of osteomyelitis and arthritis in infants}; Kaabachi O et al.; A retrospective study realised over 10 years in the orthopaedic unit of the children's hospital of Tunis allowed to collect 206 cases of osteomyelitis and arthritis in infant (3 months--3 years old) . In 74.6% of the cases, infection involved the joint . There is a single focus of the infection in 92.6% of the cases, more often at the lower limbs . The pathogen has been isolated in 33% of the cases . Staphylococcus aureus (52 %) is the more frequent pathogen, especially in osteomyelitis . Enterobateria (16%), Streptococcus (17.7%) (Streptococcus pneumonia: 10.7%), and Hemophylus influenzea (5.3%) were often isolated in arthritis.

No Shinkei Geka, 2003 Jan, 31(1), 69 - 73
{A case of multiple mycotic intracranial aneurysms}; Yagi T et al.; A patient with multiple mycotic aneurysms associated with infective endocarditis is reported . A 45-year-old man was admitted on February 16, 2001 under the diagnosis of infective endocarditis . After alpha-streptococcus was identified by a blood culture, he was treated with high doses of antibiotics . However, 2 weeks after admission, he suddenly suffered from headache and mild left hemiparesis . A CT showed a parenchymal hematoma in the right parietal lobe . Cerebral angiography demonstrated aneurysms of the bilateral middle cerebral artery and the left posterior cerebral artery . At first, we trapped and resected the ruptured right middle cerebral aneurysm . After the surgery, we tried to treat two unruptured aneurysms by endovascular treatment . During the provocation test for the posterior cerebral artery, the arterial wall was perforated by a guide wire . The parent artery was occluded by coils at this site . Although the aneurysm was still filled by retrograde blood flow, it finally disappeared six months after treatment . The left middle cerebral artery aneurysm could not be treated because the provocation test showed cognitive deficits . The patient recovered from infective endocarditis after four-months of antibiotic therapy; and the unruptured aneurysm had not changed in size for 11 months . Recently, the outcome of patients with intracranial mycotic aneurysm is improved by development of multimodality management . Especially, endovascular therapy may become an effective treatment for unruptured aneurysms, but it is necessary to take risks, such as arterial perforation into consideration.

Emerg Infect Dis, 2003 Jan, 9(1), 1 - 9
Maintaining fluoroquinolone class efficacy: review of influencing factors; Scheld WM; Previous experience with antimicrobial resistance has emphasized the importance of appropriate stewardship of these pharmacotherapeutic agents . The introduction of fluoroquinolones provided potent new drugs directed primarily against gram-negative pathogens, while the newer members of this class demonstrate more activity against gram-positive species, including Streptococcus pneumoniae . Although these agents are clinically effective against a broad range of infectious agents, emergence of resistance and associated clinical failures have prompted reexamination of their use . Appropriate use revolves around two key objectives: 1) only prescribing antimicrobial therapy when it is beneficial and 2) using the agents with optimal activity against the expected pathogens . Pharmacodynamic principles and properties can be applied to achieve the latter objective when prescribing agents belonging to the fluoroquinolone class . A focused approach emphasizing "correct-spectrum" coverage may reduce development of antimicrobial resistance and maintain class efficacy.

Biol Chem, 2002 Nov, 383(11), 1701 - 13
In vitro and in vivo stability of the epsilon2zeta2 protein complex of the broad host-range Streptococcus pyogenes pSM19035 addiction system; Camacho AG et al.; Streptococcus pyogenes pSM19035-encoded epsilon (10.7 kDa) and zeta (32.4 kDa) proteins are necessary to secure stable plasmid inheritance in bacteria, with zeta acting as toxin that kills plasmid-deprived cells and epsilon as an antitoxin that neutralises the activity of zeta . The epsilon and zeta proteins co-purify as a stable complex that, according to analytical ultracentrifugation and gel filtration, exists as epsilon2zeta2 heterotetramer in solution . Co-crystals of the epsilon2zeta2 complex contain epsilon and zeta in 1:1 molar ratio . Unfolding studies monitoring circular dichroic and fluorescence changes show that the zeta protein has a significantly lower thermodynamic stability than the epsilon protein both in free state and in the complex . Proteolytic studies indicate that zeta protein is more stable in the epsilon2zeta2 complex than in the free state . In vivo studies reveal a short half-life of the epsilon antitoxin (-18 min) and a long lifetime of the zeta toxin (>60 min) . When transcription-translation of a plasmid containing the epsilon and zeta genes was inhibited, cell death was observed after a short lag phase that correlates with the disappearance of the epsilon protein from the background.

Can J Vet Res, 2003 Jan, 67(1), 52 - 5
Clonal distribution of an atypical MRP+, EF*, and suilysin+ phenotype of virulent Streptococcus suis serotype 2 strains in Brazil; Martinez G et al.; Streptococcus suis is considered one of the most important bacterial swine pathogens worldwide . The distribution of the 35 described serotypes in diseased animals may vary in different regions . Data regarding S . suis isolation from pigs in South America is not available . In the present study, 51 isolates of S . suis recovered in pure culture or as the predominant species from diseased animals in Brazil, were analyzed . These isolates were classified as serotypes 2 (58.8%), 3 (21.5%), 7 (13.7%), 1 (3.9%), and 14 (2%) . Serotype 2 isolates were further studied for their production of virulence-related proteins muramidase-released protein (MRP), extracellular factor (EF), and suilysin . In addition, the genetic diversity was studied by randomly amplified polymorphic DNA . All but 1 of the serotype 2 isolates showed a clonal distribution of an atypical phenotype (MRP+, EF*, suilysin+), different from the known European (MRP+, EF+, suilysin+), and North American (MRPv, EF-, suilysin-), phenotypes.

Inhal Toxicol, 2003 Feb, 15(2), 131 - 50
Effects of inhaled ambient particulate matter on pulmonary antimicrobial immune defense; Zelikoff JT et al.; Respiratory-tract infection, specifically pneumonia, contributes substantially to the increased morbidity and mortality among elderly individuals exposed to airborne particulate matter of <10 microm diameter (PM(10)) . These epidemiological findings suggest that PM(10) may act as an immunosuppressive factor that can undermine normal pulmonary antimicrobial defense mechanisms . To investigate whether, and how, compromised pulmonary immunocompetence might contribute to increased mortality, two sets of laboratory studies were performed . The first examined the effects of a single inhalation exposure to concentrated ambient PM(2.5) (CAPS) from New York City air on pulmonary/systemic immunity and on the susceptibility of exposed aged rats to subsequent infection with Streptococcus pneumoniae . The second set of studies determined whether CAPS exposure, at a concentration approximating or somewhat greater than the promulgated 24-h NAAQS of 65 microg/m(3), could exacerbate an ongoing infection . Taken together, results demonstrated that a single exposure of healthy animals to CAPS had little effect on pulmonary immune function or bacterial clearance during subsequent challenge with S . pneumoniae . Alternatively, CAPS exposure of previously infected rats significantly increased bacterial burdens and decreased percentages of lavageable neutrophils and proinflammatory cytokine levels compared to those in infected filtered-air-exposed controls . These studies demonstrate that a single exposure to ambient PM(2.5) compromises a host's ability to handle ongoing pneumococcal infections and support the epidemiological findings of increased pneumonia-related deaths in ambient PM-exposed elderly individuals.

Zh Mikrobiol Epidemiol Immunobiol, 2002 Sep-Oct, (5), 3 - 6
{Frequency of genes speA, speB, and speC in Streptococcus pyogenes strains and the identification of the infective agent by polymerase chain reaction}; Dmitrieva NF et al.; In cultures of S . pyogenes isolated from patients and carriers in different territories of the Russian Federation the genes of erythorogenic toxins A, B and C (speA, speB and specC) were detected . The possibility of the identification of S . pyogenes by means of PCR on the basis of primers to erythrogenic toxin B was determined . Gene speB was detected in all S . pyogenes cultures under study and proved to be species specific . Genes speA and speC were detected, respectively, in 29.4% and 9.35% of the S . pyogenes cultures under study . A test system for the identification of S . pyogenes on the basis of primers to gene speB was developed . The prospects for the detection of genes speA and speC for intraspecific typing of this infective agent were evaluated.

Am J Respir Crit Care Med, 2003 Jan 15, 167(2), 164 - 70
Platelet endothelial cell adhesion molecule-1 in neutrophil emigration during acute bacterial pneumonia in mice and rats; Tasaka S et al.; Platelet endothelial cell adhesion molecule-1 (PECAM-1) (CD31) is an adhesion molecule believed to mediate transendothelial migration of neutrophils and other leukocytes after CD11/CD18-mediated adhesion . Our study evaluated the role of PECAM-1 in neutrophil emigration across the pulmonary capillaries and the bronchial microvasculature using blocking anti-PECAM-1 antibodies in mice and rats . Neutrophil emigration was induced by Escherichia coli, a stimulus eliciting CD11/CD18-dependent emigration, or Streptococcus pneumoniae, a stimulus inducing CD11/CD18-independent emigration . Although anti-PECAM-1 antibodies partially inhibited glycogen-induced neutrophil emigration into the peritoneum, neutrophil emigration across either the pulmonary capillaries or the bronchial microvasculature in response to either E . coli or S . pneumoniae was not prevented when the function of PECAM-1 was inhibited in either mice or rats . There was also no increase in the number of intravascular neutrophils within the bronchial vessels after treatment with anti-PECAM-1 antibody . These studies indicate that either CD11/CD18-dependent or -independent adhesion pathways may lead to PECAM-1-independent transendothelial migration through the pulmonary or the bronchial endothelium.

Clin Infect Dis, 2003 Jan 15, 36(2), e19 - 25 Epub 2003 Jan 07.
Macrolide-resistant pneumococcal endocarditis and epidural abscess that develop during erythromycin therapy; Butler JC et al.; Suppurative complications of Streptococcus pneumoniae infections have become uncommon in the antibiotic era . We report a case of pneumococcal bacteremia and pneumonia complicated with epidural abscess and endocarditis in which macrolide resistance (the MLS(B) phenotype) emerged during erythromycin therapy . Genetic determinants known to mediate the most common mechanisms of macrolide resistance (methylation of the 23S rRNA and antibiotic efflux) were not detected by polymerase chain reaction or DNA hybridization . Sequence analysis of the DNA encoding the 23S rRNA of the macrolide-resistant isolate from the patient demonstrated the replacement of adenine by thymine at position 2058 (A2058T) in 2 of 4 alleles . Clinicians should be alert to the possibility of the emergence of resistance during macrolide therapy for community-acquired pneumonia, particularly if suppurative complications of pneumococcal infection are suspected.

Clin Infect Dis, 2003 Jan 15, 36(2), 175 - 82 Epub 2003 Jan 07.
Tonsillopharyngitis caused by foodborne group A streptococcus: a prison-based outbreak; Levy M et al.; An outbreak of tonsillopharyngitis due to Streptococcus pyogenes occurred among inmates of a rural correctional center in New South Wales, Australia . A total of 72 (28%) of 256 inmates became ill in December 1999 . S . pyogenes type M-75, T-25, which was opacity factor positive, was isolated from throat swab specimens obtained from 5 of 57 inmates with primary cases and from 4 of 15 inmates with secondary cases, as well as from specimens obtained from the hand wounds and throat of one of the food handlers . The consumption of curried egg rolls (i.e., curried egg salad sandwiches) was the most likely association with this outbreak . The presumed source of the food contamination was the food handler who had infected hand wounds . There has been only one other outbreak of streptococcal pharyngitis reported from a prison . Other outbreaks have been reported from military bases, nursing homes, and community picnics.

Clin Diagn Lab Immunol, 2003 Jan, 10(1), 161 - 6
Keratinocyte expression of human beta defensin 2 following bacterial infection: role in cutaneous host defense; Dinulos JG et al.; Human beta defensin 2 (hbetaD-2) is thought to play an important role in cutaneous immune defense . We hypothesized that (i) keratinocyte expression of hbetaD-2, measured by reverse transcription-PCR, would be upregulated in response to challenge with pathogenic bacteria, particularly highly adherent strains of Streptococcus pyogenes and Staphylococcus aureus, and (ii) hbetaD-2 would have potent antimicrobial activity against pathogenic but not commensal organisms . Expression of hbetaD-2 was induced consistently by S . aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa, whereas strains of S . pyogenes were poor and variable inducers of hbetaD-2 . No correlation was found between levels of bacterial adherence and keratinocyte expression of hbetaD-2 . S . pyogenes was significantly more sensitive to killing by hbetaD-2 than S . epidermidis . We conclude that the ability to induce hbetaD-2 expression in combination with sensitivity to its antimicrobial effects may contribute to the rarity of skin infections with the gram-negative bacterial organisms, whereas lack of stimulation of hbetaD-2 expression by S . pyogenes may be important in its ability to evade innate defenses and cause skin disease . Induction of expression of hbetaD-2 but relative tolerance to it may enable S . epidermidis to survive on the skin surface and modulate hbetaD-2 expression when the stratum corneum barrier is disrupted.

Clin Diagn Lab Immunol, 2003 Jan, 10(1), 125 - 32
Identification of B- and T-cell epitopes of BB, a carrier protein derived from the G protein of Streptococcus strain G148; Goetsch L et al.; Most conventional vaccines consist of killed organisms or purified antigenic proteins . Such molecules are generally poorly immunogenic and need to be coupled to carrier proteins . We have identified a new carrier molecule, BB, derived from the G protein of Streptococcus strain G148 . We show that BB is able to induce strong antibody responses when conjugated to peptides or polysaccharides . In order to localize T and B cell epitopes in BB and match them with the albumin-binding region of the molecule, we immunized mice with BB, performed B and T pepscan analyses, and compared the results with pepscan done with sera and cells from humans . Our results indicate that BB has two distinct T helper epitopes, seven linear B-cell epitopes, and one conformational B-cell epitope in BALB/c mice . Four linear B-cell epitopes were identified from human sera, three of which overlapped mouse B-cell epitopes . Finally, three human T-cell epitopes were detected on the BB protein . One of these T-cell epitopes is common to BALB/c mice and humans and was localized in the region that contains the albumin-binding site . These data are of interest for the optimization of new carrier molecules derived from BB.

J Obstet Gynaecol, 2001, 21(1), 21 - 23
Variations in the investigation and management of group B streptococcus in Scotland; J Moss A M Mathers S Bjornsson A D Cameron Jacky Williams Jill Pell H; This article describes the practice of Scottish obstetricians in terms of their investigation and treatment of group B streptococcus (GBS) . This was a postal questionnaire survey of all 125 consultant obstetricians in Scotland . We recorded indications for testing for GBS, categories of women to whom treatment is given empirically and following confirmed infection, type of antibiotic used, and timing and route of administration . No respondents screened all pregnant women but 97% screened some or all of those at highest risk . Three-quarters administered antibiotics empirically to women with intrapartum pyrexia . However, other high-risk groups were unlikely to receive treatment without confirmation of colonisation . Only one-third of respondents gave antibiotics to all women with confirmed GBS, and up to one-half withheld them from some colonised women in high-risk groups . Contrary to US guidelines, only 29% tested for GBS using low vaginal swabs and only 13% administered intrapartum antibiotics intravenously . There are wide variations in investigating and treating GBS throughout Scotland . It is likely that similar variations exist throughout the United Kingdom . UK guidelines are required to reduce variations and ensure appropriate and effective management.

Clin Exp Immunol, 2003 Jan, 131(1), 8 - 16
After chemotherapy, functional humoral response capacity is restored before complete restoration of lymphoid compartments; Zandvoort A et al.; Chemotherapy has, besides the beneficial effects, several adverse effects . Suppression of the immune system is one of the most important problems . Infections caused by encapsulated bacteria like Streptococcus pneumoniae are responsible for a major part of infectious problems during and after treatment . The splenic marginal zone is essential in the initiation of an immune response to encapsulated bacteria . In this study, we analysed the effects of three different cytostatic agents on humoral immune responses . We found a reduced, but detectable immune response capacity at two days after treatment although the marginal zone B cell population is severely reduced at this time point . Twenty-four days after cessation of treatment, the immune response capacity was largely restored although lymphoid compartments were still not completely restored at that time point . Apparently, the presence of only few marginal zone B cells is sufficient to evoke a rise in antibody titres and although antibody titre increases are low, even small rises are most likely clinically relevant.

Clin Microbiol Infect, 2002, 8 Suppl 3, 9 - 20; discussion 33-5
The era of antimicrobial resistance-implications for the clinical laboratory; Low DE; The emergence of resistance to antimicrobial drugs in a range of bacterial pathogens of the respiratory tract creates a challenge for the clinical diagnostic laboratory . Resistance to macrolides among strains of Streptococcus pneumoniae has reached high levels in many countries . There are two main types of resistance mechanisms, one (MLSB phenotype) leading to high-level resistance and the other (M phenotype) resulting in a lower level of resistance . As there are indications that high-level resistance may have clinical relevance, it is important to be able to detect such strains . This is now possible with the erythromycin/clindamycin double disc diffusion test . Although resistance to beta-lactams has also increased, there is now evidence that some beta-lactams are still effective against isolates that have low-level resistance . In response to these observations, new breakpoints have now been introduced by the National Committee for Clinical Laboratory Standards (NCCLS) for amoxicillin, cefotaxime and ceftriaxone, which increase the percentage of pneumococcal isolates that can still be treated effectively with these agents . As a consequence of the increasing use of fluoroquinolones, resistance has now emerged to this group of compounds and this has been associated with clinical failures . Although standard minimum inhibitory concentration tests can detect strains with high levels of resistance (double step mutants) they are not reliable in detecting strains with a single mutation . This is important as there is increasing evidence that strains with a single mutation in the target topoisomerase are even more likely to develop a second mutation, leading to higher levels of resistance and thus probably, therapeutic failure . Because resistance to fluoroquinolones is currently low in the US, the NCCLS does not recommend that susceptibility testing with the newer respiratory fluoroquinolones be carried out routinely . However, since the respiratory fluoroquinolones have in fact become the first line of therapy for the treatment of community-acquired pneumonia, it may now be time to institute routine testing of clinical isolates of pneumococci to these agents . Simple techniques for the clinical diagnostic laboratory to enable these first-step mutants to be detected are urgently required.

Afr J Med Med Sci, 2002 Jun, 31(2), 141 - 3
A possible outbreak of Streptococcus pneumoniae invasive infection in children in Ibadan, Nigeria; Fashae KF et al.; Streptococcus pneumoniae is an important aetiological agent of infections in children worldwide . The isolation rate of the bacteria has been strikingly low in the recent past in Nigeria . In a study of 1000 blood samples from patients, out of which 642 were from children in Ibadan between May 1999 and December 2000, 14 isolates of Streptococcus pneumoniae were obtained (a prevalence rate of 1.4%) . All the isolates were from children and clustered between 13th September and 22nd October 1999, period of 40 days and thereafter no more organisms were isolated . Antibiotic sensitivity testing of all isolates by disc diffusion method showed resistance to cotrimoxazole, tetracycline and penicillin to be 14%, 21% and 36% respectively . All the isolates were sensitive to chloramphenicol and erythromycin . No fatalities were recorded among the children . This may have indicated an outbreak and underscores the urgency for an epidemiological database in Nigeria to ascertain the exact clinical burden of S . pnemoniae infections so as to determine the appropriate vaccine strategies required for Nigerian children.

J Clin Microbiol, 2003 Jan, 41(1), 512 - 3
Meningitis due to mixed infection with penicillin-resistant and penicillin-susceptible strains of Streptococcus pneumoniae; Chaves F et al.; Streptococcus pneumoniae is the major cause of bacterial meningitis . We report a case of meningitis due to a mixed infection with two distinct strains of S . pneumoniae: one penicillin-resistant strain of serotype 9V and one penicillin-susceptible strain of serotype 7 . The two strains exhibited different pulsed-field gel electrophoresis profiles.

J Clin Microbiol, 2003 Jan, 41(1), 386 - 92
Stability of serotypes during nasopharyngeal carriage of Streptococcus pneumoniae; Meats E et al.; Serotype changes among natural isolates of Streptococcus pneumoniae are well documented and occur by recombinational exchanges at the capsular biosynthetic locus . However, the frequency with which this phenomenon occurs within the nasopharynx of children is not clear and is likely to be highest in the nasopharynx of children, who have high rates of pneumococcal carriage . A birth cohort of 100 infants was studied, and pneumococci were recovered from nasopharyngeal samples taken at monthly intervals during the first 6 months of life and then at 2-monthly intervals until the age of 2 years . Among the 1,353 nasopharyngeal samples were 523 that contained presumptive pneumococci, and three colonies from each were serotyped . A total of 333 isolates, including all isolates of differing serotypes from the same child, were characterized by multilocus sequence typing . Sixty-eight children carried multiple serotypes during the first 2 years of life . Two children carried a typeable and a nonserotypeable pneumococcus of identical genotype, and five children carried genetically indistinguishable isolates of serotypes 15B and 15C . These isolates were considered, respectively, to be due to loss of capsule expression and the known ability of serotype 15B and 15C pneumococci to interconvert by loss or gain of an acetyl group on the capsular polysaccharide . In all other cases, isolates from the same children that differed in serotype also differed in genotype, indicating the acquisition of a different pneumococcal strain rather than a change in capsular type . There was therefore no evidence in this study for any change of serotype due to recombinational replacements at the capsular locus among the pneumococci carried within the nasopharynges of the children.

Obstet Gynecol, 2003 Jan, 101(1), 74 - 9
Correlates of antibiotic-resistant group B streptococcus isolated from pregnant women; Manning SD et al.; Despite antibiotic prophylaxis for at-risk mothers during labor and delivery, group B streptococcus still causes substantial morbidity and mortality among newborns . Resistance to antibiotics recommended for penicillin-allergic pregnant women, such as erythromycin and clindamycin, has increased . A better understanding of factors associated with group B streptococcus resistance is essential to effectively prevent group B streptococcus disease.A total of 117 sequential group B streptococcus isolates were obtained between August 1999 and March 2000 from pregnant women at the University of Michigan Medical Center . Serotype and susceptibility to ten antimicrobials using disk diffusion with E-test for confirmation were determined, and the association between several host factors and colonization with a resistant strain was evaluated.Group B streptococcus was frequently resistant to erythromycin (29%) and clindamycin (21%) but was susceptible to all other antimicrobials tested . A stepwise logistic regression model revealed that black ethnicity (P =.02) and carriage of a serotype V strain (P =.01) were associated with group B streptococcus resistance.Among this population of pregnant women, black ethnicity and serotype V were the strongest predictors of colonization with an erythromycin- or clindamycin-resistant group B streptococcus strain . A better understanding of factors associated with antibiotic resistance is needed to minimize group B streptococcus disease risks and to maximize effective chemoprophylaxis.

Ann Thorac Cardiovasc Surg, 2002 Dec, 8(6), 350 - 3
Avoiding the pump in tricuspid valve endocarditis--vegetectomy under inflow occlusion; Raman J et al.; BACKGROUND: Surgical treatment of tricuspid valve endocarditis (TVE) ranges from vegetectomy to valve replacement with the use of cardiopulmonary bypass (CPB), accompanied by risks of systemic and lung complications . We present our experience with tricuspid valve vegetectomy under inflow occlusion without CPB . METHODS: Between July 1998 and July 2001, seven patients with a mean age of 26 years underwent tricuspid valve vegetectomy under vena caval inflow occlusion (VCIO) . Five patients were intravenous drug users . None of them had left-sided heart valve involvement . The clinical indications for operating were recurrent septic pulmonary emboli with significant bilateral lung infiltrates and intractable infection with signs of severe systemic sepsis, despite treatment with appropriate intravenous antibiotics for a mean duration of 126 hours . The echocardiographic indication was very large localized >1 cm vegetations in all patients . Six patients had methicillin sensitive staphylococcus aureus and one had streptococcus viridans positive blood cultures . Five patients had postoperative high volume veno-venous hemofiltration (HVVF) . RESULTS: There were no deaths . VCIO time did not exceed 2 minutes (range time was 45 seconds to 2 minutes) . All patients had resolution of sepsis and improvement in respiratory status within 48 hours . Five patients had trivial and two moderate tricuspid regurgitation . Six patients were discharged home within 14 days with no long-term sequelae . One patient required long-term dialysis for renal failure . One patient required a late thoracotomy for drainage of a loculated empyema . CONCLUSIONS: Tricuspid valve vegetectomy can be performed safely under VCIO . HVVF promotes removal of inflammatory mediators, thus improving recovery.

Clin Infect Dis, 2003 Jan 15, 36(Suppl 1), S11 - 23
Bacterial resistance: origins, epidemiology, and impact; Livermore DM; The basic mechanisms of antibacterial resistance are well known, but critical new aspects continue to be discovered . Recently discovered factors with major implications for the emergence, dissemination, and maintenance of resistance include multidrug efflux, hypermutability, integrons, and plasmid addiction . Some resistances are widespread and others local, with prevalence rates often worst in newly prosperous countries and in those specialist units where antibacterial use is heaviest . Multidrug-resistant epidemic strains are critical to the total accumulation of resistance (e.g., among Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae), but it remains unclear why some bacterial lineages achieve epidemic spread whereas others that are equally resistant do not . The correlation between in vitro resistance and treatment failure is imperfect, but resistance undoubtedly increases mortality, morbidity, and costs in many settings . Recent concern has led to a plethora of governmental and agency reports advocating less antibacterial use, better antibacterial use, better infection control, and the development of new antibacterials . The evidence that better prescribing can reduce resistance rates is mixed, and although changes to hospital regimens may reduce one resistance problem, other opportunistic bacteria may fill the vacant niche . Overall, the best that can reasonably be anticipated is an improved balance between the accumulation of resistance and new antibacterial development.

Biotechnol Appl Biochem, 2003 Jun, 37(Pt 3), 283 - 7
Purification of capsular polysaccharide from Streptococcus pneumoniae serotype 23F by a procedure suitable for scale-up; Goncalves VM et al.; Streptococcus pneumoniae is a pathogenic encapsulated bacterium, which causes pneumonia, bacteraemia and meningitis . Capsular polysaccharide conjugated to a carrier protein has been widely used as a vaccine antigen . Serotype 23F is one of the prevalent worldwide pneumococci . A simple and efficient method for capsular polysaccharide serotype 23F purification that can easily be scaled-up was developed . This method consisted of using culture broth obtained by tangential microfiltration through a 0.22 microm membrane, broth microfiltrate concentration by tangential ultrafiltration in a 30 kDa spiral membrane, fractional ethanol precipitation (28-60%), nuclease and proteinase treatment, and concentration/diafiltration in a 30 kDa cassette membrane . The final polysaccharide recovery was 89% . The final protein and nucleotide contamination was 1.5% (w/w) and 0.3% (w/w) respectively . The final pure polysaccharide meets the requirements of the World Health Organization and residual proteinase was not found in the final product.

Drugs, 2003, 63(2), 181 - 205
International guidelines for the treatment of community-acquired pneumonia in adults: the role of macrolides; File TM Jr et al.; The significance of community-acquired pneumonia (CAP) has led to the publication of guidelines from numerous international organisations . Because the macrolide class of antimicrobials is active against most of the key pathogens associated with CAP, agents from this class are commonly included in recommendations from these guidelines . However, there are differences among the various guidelines concerning the positioning of the macrolides for empirical therapy . An important factor concerning the use of macrolides for CAP is the emergence of resistance of Streptococcus pneumoniae over the past decade . The rate of S . pneumoniae resistance to macrolides ranges from 4 to 70% of strains in worldwide surveillance studies . The most common mechanisms of resistance include methylation of a ribosomal target encoded by the erm gene and efflux of the macrolides by a cell membrane protein transporter, encoded by the mef gene . S . pneumoniae strains with the mef gene are resistant at a lower level (with minimum inhibitory concentration {MIC} values generally 1-16 microg/ml) than erm resistant strains; and it is possible that such strains may be inhibited if sufficiently high levels of macrolide can be obtained at the infected site . Currently mef-associated resistance predominates in North America, whereas erm predominates in Europe . Until recently, reports of failure of treatment of CAP with macrolides has been rare, particularly for patients with low-risk for drug-resistant strains . However, since 2000, several patients treated with an oral macrolide who have subsequently required admission to the hospital for macrolide-resistant S . pneumoniae (MRSP) bacteraemia have been reported in the literature . Major issues, which are fundamental to the use of the macrolides as recommended in the various guidelines, include the importance of providing therapy for 'atypical' pathogens and the clinical significance of MRSP . Presently, the macrolides are more prominently recommended in the North American guidelines than in other parts of the world . The difference in the emphasis placed on the importance of the atypical pathogens as well as the expression of MRSP in North America compared with Europe partly explains this variance.

Zhongguo Zhong Yao Za Zhi, 2000 Jul, 25(7), 391 - 4
{An preliminary comparative study on physiological activity of Fritillaria pallidiflora Schrek . and F . delavayi Franch}; Xu HB et al.; OBJECTIVE: To compare the physiological activity of Fritillaria pallidiflora alkaloids(FPA) with that of F . delavayi alkaloids(FDA) . METHOD: Xylene-induced ear swelling in mice, SO2-induced cough in mice, expectorant experiment on phenolsulfon phthalein excretion and bacteria incubation in vitro, etc . RESULT: The total alkaloids of both FPA and FDA(i.g., 400 mg.kg-1 and 200 mg.kg-1) have anti-inflammatory, antibechic and expectorant effects, but the former is more effective than the latter . Given the same dosage, FPA is still more effective than FDA . FPA can inhibit Hemophilus influenzae, Staphylococcus aureus and Streptococcus pneumoniae, etc, more effectively than FDA . CONCLUSION: In anti-inflammatory, antibechic, expectorant and bacteriostatic effects FPA is superior to FDA.

ASDC J Dent Child, 2002 May-Aug, 69(2), 133 - 7, 123
Periodontal diseases, caries, and microbial composition of the subgingival plaque in children: a longitudinal study; Bimstein E et al.; The present study compares periodontal parameters, caries, and levels of colony forming units (CFU) of bacteria from subgingival plaque of permanent teeth, to those of primary teeth examined 4 years previously . Six children who had periodontitis and 5 who had no periodontitis in primary teeth (groups A and B respectively) were examined . The microbial examination included the number of CFU of the total anaerobic count, Actinobacillus actinomycetemcomitans, Streptococcus mutans and Porphyromonas gingivalis . The differences in CFU values for the permanent teeth between groups A and B were not significant . Group A had significantly higher gingival inflammation values in the permanent teeth than group B . Permanent teeth had significantly higher CFU values of P . gingivalis than the primary teeth . Based on the present limited sample, the number of CFU from bacteria of the subgingival plaque of primary teeth are not an adequate predictor of periodontal disease or caries in the permanent teeth.

EMBO J, 2003 Jan 15, 22(2), 183 - 92
Structure of 23S rRNA hairpin 35 and its interaction with the tylosin-resistance methyltransferase RlmAII; Lebars I et al.; The bacterial rRNA methyltransferase RlmAII (formerly TlrB) contributes to resistance against tylosin-like 16-membered ring macrolide antibiotics . RlmAII was originally discovered in the tylosin-producer Streptomyces fradiae, and members of this subclass of methyltransferases have subsequently been found in other Gram-positive bacteria, including Streptococcus pneumoniae . In all cases, RlmAII methylates 23S rRNA at nucleotide G748, which is situated in a stem-loop (hairpin 35) at the macrolide binding site of the ribosome . The conformation of hairpin 35 recognized by RlmAII is shown here by NMR spectroscopy to resemble the anticodon loop of tRNA . The loop folds independently of the rest of the 23S rRNA, and is stabilized by a non-canonical G-A pair and a U-turn motif, rendering G748 accessible . Binding of S.pneumoniae RlmAII induces changes in NMR signals at specific nucleotides that are involved in the methyltransferase-RNA interaction . The conformation of hairpin 35 that interacts with RlmAII is radically different from the structure this hairpin adopts within the 50S subunit . This indicates that the hairpin undergoes major structural rearrangement upon interaction with ribosomal proteins during 50S assembly.

Drugs Exp Clin Res, 2002, 28(4), 165 - 8
Various Streptococcus species isolated from infectious skin diseases; Higaki S et al.; An evaluation was carried out of the types of Streptococcus spp . (excluding Streptococcus pyogenes) isolated from infectious skin diseases, and their susceptibilities to eight antimicrobial drugs of the Streptococcus spp . isolated . The types of diseases were also evaluated . A total of 29 Streptococcus spp . were identified and Streptococcus agalactiae was the most common . Streptococcus spp . were found to be susceptible to the eight antimicrobials used except gentamicin; susceptibility to gentamicin varied according to species . Susceptibility to beta-lactams was 100% and this drug should be considered the antimicrobial of choice in Streptococcus spp . treatment.

J Clin Invest, 2003 Jan, 111(1), 61 - 70
A novel streptococcal surface protease promotes virulence, resistance to opsonophagocytosis, and cleavage of human fibrinogen; Harris TO et al.; Group B streptococcus (GBS) is an important human pathogen . In this study, we sought to identify mechanisms that may protect GBS from host defenses in addition to its capsular polysaccharide . A gene encoding a cell-surface-associated protein (cspA) was characterized from a highly virulent type III GBS isolate, COH1 . Its sequence indicated that it is a subtilisin-like extracellular serine protease homologous to streptococcal C5a peptidases and caseinases of lactic acid bacteria . The wild-type strain cleaved the alpha chain of human fibrinogen, whereas a cspA mutant, TOH121, was unable to cleave fibrinogen . We observed aggregated material when COH1 was incubated with fibrinogen but not when the mutant strain was treated similarly . This suggested that the product(s) of fibrinogen cleavage have strong adhesive properties and may be similar to fibrin . The cspA gene was present among representative clinical isolates from all nine capsular serotypes, as revealed by Southern blotting . A cspA(-) mutant was ten times less virulent in a neonatal rat sepsis model of GBS infections, as measured by LD(50) analysis . In addition, the cspA(-) mutant was significantly more sensitive than the wild-type strain to opsonophagocytic killing by human neutrophils in vitro . Taken together, the results suggest that cleavage of fibrinogen by CspA may increase the lethality of GBS infection, potentially by protecting the bacterium from opsonophagocytic killing.

J Bacteriol, 2003 Jan, 185(2), 683 - 7
ClpP of Streptococcus salivarius is a novel member of the dually regulated class of stress response genes in gram-positive bacteria; Chastanet A et al.; Nucleotide sequence analysis of the Streptococcus salivarius clpP locus revealed potential binding sites for both the CtsR and HrcA repressors . Dual regulation by HrcA and CtsR was demonstrated by using Bacillus subtilis as a heterologous host, and CtsR was shown to bind directly to the clpP promoter sequence . This is the first example of a clpP gene under the control of HrcA.

J Bacteriol, 2003 Jan, 185(2), 413 - 21
Transcriptional regulation in the Streptococcus pneumoniae rlrA pathogenicity islet by RlrA; Hava DL et al.; The proper temporal expression of virulence genes during infection is crucial to the infectious life cycle of microbial pathogens, particularly in pathogens that encounter a multitude of environments in eukaryotic hosts . Streptococcus pneumoniae normally colonizes the nasopharynges of healthy adults but can cause a range of diseases at a variety of host sites . Transcriptional regulators that are essential for full virulence of S . pneumoniae in different animal models have been identified . One such regulator, rlrA, is required for colonization of the nasopharynx and lung infection but is dispensable for systemic infection . Previous work has shown that rlrA lies in a 12-kb pathogenicity islet, divergently opposed to three putative sortase-anchored surface proteins and three sortase enzymes . In addition to rlrA, one of the putative surface proteins and one of the sortases have also been shown to be essential for lung infection . In this work, we demonstrate that RlrA is a positive regulator of all seven genes in the rlrA pathogenicity islet, with transcriptional activation occurring at four different promoters in the islet with AT-rich sequences . These promoters direct the expression of rlrA itself, the three sortases, rrgA, and rrgBC . These data are consistent with the model whereby the rlrA pathogenicity islet acts in an autonomous manner to alter the bacterial surface components that interact with the pulmonary and nasopharyngeal environments.

Kansenshogaku Zasshi, 2002 Nov, 76(11), 958 - 62
{A case of bacteremic group A streptococcus infection with organ dysfunction following a minor skin abrasion}; Fukuoka M et al.; A 20-year-old male was admitted to our hospital with the chief complaints of high fever and pain around his right hip joint . He had his right knee injured with a slight abrasion three weeks before . The diagnosis of suppurative lymphadenitis of inguen was made, and intravenous cefotiam was started . Despite these treatments his fever continued, general edema and dry cough appeared . Arterial blood gas showed severe hypoxia and chest X ray revealed marked cardiomegaly associated with ground-glass opacity over bilateral lower pulmonary fields . Slight renal insufficiency was also observed . On the fifth hospital day, the culture specimens of both blood and pus from the abrasion on admission yielded Streptococcus pyogenes . His condition was diagnosed as severe group A Streptococcus infection, then antibiotics were switched to intravenous administration of high dose aminobenzyl penicillin and clindamycin in combination with protease inhibitor, urinastatin . After these treatments, his condition improved and he was discharged from the hospital after one month . Group A Streptococcus may cause uncommon but life-threatening infection such as septicemia . Early recognition of the disease and prompt initiation of appropriate treatment may lead to successful outcome.

Ann Ig, 2002 Sep-Oct, 14(5), 373 - 88
{Cost-of-illness study of pneumococcal disease in Italian children}; Colombo GL; Streptococcus pneumoniae (S pneumoniae, or pneumococcus) is a leading cause of illness in children, and causes illness and death among the elderly and persons with certain underlying conditions . A Cost-of-Illness (COI) estimate for each pneumococcal disease (meningitis, bacteremia, pneumonia, and otitis media) was determined using decision tree analysis that considered both direct and indirect costs . Information on the burden of pneumococcal disease in Italy, in terms of data on the incidence and seroprevalence of disease was collected from published and unpublished records, supplemented, and verified by Italian pediatric and infectious disease experts . The annual cost to society of caring for children with pneumococcal disease is estimated to be around 59,604,477 euro including both direct costs and indirect costs (productivity changes) . Direct costs accounted for 39.9% of the total costs . The value of resources used to treat otitis media was 60.6% of the total direct costs; 31.9% was the value of resources for treating pneumonia; 6.5% for treating bacteremia; 1.0% for treating meningitis . A sensitivity analysis confirmed the robustness of the results.

Ann Ig, 2002 Sep-Oct, 14(5), 361 - 71
{Antibiotic microbial resistance surveillance in invasive infections caused by Streptococcus pneumoniae and Staphylococcus aureus: the EARSS (European Antimicrobial Resistance Surveillance System) project in Italy (April 1999-April 2000)}; Moro ML et al.; This paper presents the results of an Italian multicentric study conducted in the period April 1999-April 2000 in 64 clinical microbiology laboratories, aimed at collecting antimicrobial resistance data using a standard European protocol (EARSS Project, European Antimicrobial Surveillance System) . A total of 1701 strains of Staphylococcus aureus were isolated from blood and 367 strains of Streptococcus pneumoniae were isolated from blood (72.7%) or from CSF (27.3%) . Methicillin resistance in S . aureus was found to be 42.1%; it was significantly higher in adults (RR = 6.6, CI 95% 2.5-17.0), in hospitals of Centre and North of Italy (respectively RR = 1.45, CI 95% 1.1-2.0; RR = 1.6, CI 95% 1.1-2.2), and in intensive care and surgery units (respectively RR = 1.8, IC 95% 1.6-2.0 and RR = 1.7, CI 95% 1.4-1.9) . Penicillin resistance in S . pneumoniae was found to be 12.1%; it was higher in South Italy (RR = 3.5, CI 95% 1.9-6.6, in meningitis compared to sepsis (RR = 2.5, CI 95% 1.4-2.5) and in intensive care units compared to other departments (RR = 2.2, CI 95% 1.0-4.8) . The level of erythromycin resistance in S . pneumoniae was of 28.2%, reaching 56.4% in penicillin resistant strains . These results suggest that a continued surveillance and effective control measures are required.

Int J Antimicrob Agents, 2003 Jan, 21(1), 67 - 70
Clinical isolates of macrolide-resistant Streptococcus pyogenes in Central Greece; Petinaki E et al.; A total of 300 Streptococcus pyogenes isolates, collected during 2001 from five hospitals in the Thessalia district (Central Greece), were examined for their resistance to macrolides . Resistance to erythromycin was detected in 58 isolates (19.3%) . Of these, 68.9% were susceptible to clindamycin (M-phenotype) and carried the mefA gene . Of the remaining isolates, 18 expressed the MLS(B) phenotype: 12 and six exhibited inducible and constitutive resistance to clindamycin, respectively . All of these strains were found to be ermA(TR) positive, except for four that had the ermB gene . Of the erythromycin-resistant strains, none was found to be resistant to penicillin, tetracycline or quinupristin-dalfopristin . Molecular typing by PFGE showed the presence of a limited number of clones.

Int J Oral Maxillofac Implants, 2002 Nov-Dec, 17(6), 793 - 8
Bacterial colonization of zirconia ceramic surfaces: an in vitro and in vivo study; Rimondini L et al.; PURPOSE: The microbial colonization of new ceramic materials developed for abutment manufacturing was assessed . MATERIALS AND METHODS: The materials used in these experiments were disks of 'as-fired' and 'rectified' ceramic material made of tetragonal zirconia polycrystals stabilized with yttrium (Y-TZP) and commercially pure grade 2 titanium (Ti) with corresponding eluates . They were tested in vitro with the following bacteria: Streptococcus mutans, S . sanguis, Actinomyces viscosus, A . naeslundii, and Porphyromonas gingivalis . Proliferation was evaluated on plates by inhibitory halos around pits, previously inoculated with eluates obtained from the materials . Bacterial adhesion on materials was quantified by spectrophotometric evaluation of the slime production by the same bacteria . Moreover, early bacterial adhesion was evaluated in human volunteers and observed with SEM . RESULTS: No inhibition of bacterial proliferation using eluates was observed . In vitro as-fired and rectified Y-TZP showed significantly more adherent S . mutans than did Ti disks, while S . sanguis seemed to adhere easily to Ti specimens . No differences were noted for Actinomyces spp and P . gingivalis . In vivo Y-TZP accumulated fewer bacteria than Ti in terms of the total number of bacteria and presence of potential putative pathogens such as rods . No differences were observed between rectified and as-fired Y-TZP . DISCUSSION: Overall, Y-TZP accumulates fewer bacteria than Ti . CONCLUSION: Y-TZP may be considered as a promising material for abutment manufacturing.

Eur J Oral Sci, 2002 Dec, 110(6), 434 - 8
Influence of dentifrices and dietary components in saliva on wettability of pellicle-coated enamel in vitro and in vivo; van der Mei HC et al.; In vitro salivary pellicles were found to be less hydrophobic by water contact angles than clinically formed pellicles . In this study, water contact angles were measured on enamel coated with pellicles adsorbed from reconstituted human whole saliva (RHWS) and after exposure to dentifrices or dietary components . In addition, adhesion of Streptococcus oralis J22 to pellicles formed from RHWS with minor amounts of milk added and after exposure to dentifrices was studied . Exposure of RHWS-pellicles to milk or salad oil yielded an increase in the hydrophobicity of in vitro pellicles to values observed in vivo, but a decrease was seen after exposure to a sugar solution . Pellicles formed from saliva with 0.4% milk added attracted less S . oralis cells than pellicles formed in the absence of milk components . Exposure of pellicles formed from saliva with milk added to various dentifrices had a variable effect on bacterial adhesion: markedly lower numbers of adhering S . oralis were found for a dentifrice with NaF, but exposure to dentifrices containing SnF2 or hexametaphosphate showed slightly increased adhesion . In summary, dietary components have influence on the hydrophobicity of enamel pellicles, while combinations of dietary components and dentifrices certainly influence the adhesiveness of the pellicles . The effects of dietary components on pellicle conditioning film should be taken into consideration in research on the development of ingredients to control intraoral surface chemistry and microbiology, as well as in the development of oral products.

Pathol Biol (Paris), 2002 Dec, 50(10), 595 - 8
{Rhône-Alpes observatory of Streptococcus pneumoniae in 1999: 35 cases of meningitis}; Chomarat M et al.; In 1999, in Rhone-Alpes region, in a survey of resistance to antibiotics of Streptococcus pneumoniae, 35 cases of meningitis were observed . A retrospectic questionnary was sent to each participant . MICs to Penicillin, Amoxicillin and Cefotaxime were determined with ATB-PNEUMO gallery or E-test and by disk diffusion for the other antibiotics . The results were interpreted according to the recommendations of the CA-SFM . Mean age was 38.1 years (range : 1 month -78 years) and sex-ratio 2/5 . Eight patients had previously received antibiotics, 22 patients had risk factors and 23 were transferred in intensive care unit . The patients received C3G + glycopeptide in 15 of 16 children and in 13/19 adults according to the consensus recommendations . Diagnostic was made on the direct examination of CSF in 83%, and blood cultures was positive in 74.3% of cases . The percentage of PRP was 48.6% with 17.1% of intermediate-amoxicilline and 14.3% intermediate-cefotaxime strains . Resistance to trimethoprim-sulfamethoxazole was 45.7%, to chloramphenicol 30% and to fosfomycin 6.9% . All the strains were susceptible to rifampicin and vancomycin . Among the 17 PRP strains, 7 were belonging to serotype 6 (6 in children) . The clinical outcome was fatal in 7 male cases (20%), without risk factors in 3 children and 6 of 7 strains were susceptible to penicillin . Six patients (17%) had auditive and/or neurologic sequellaes . This study shows that nearly 50% of strains isolated in meningitis, in Rhone-Alpes region, were not susceptible to penicillin, and confirms the frequency of sequellaes while the mortality is not related with the resistance of strains to the antibiotics.

Environ Int, 2002 Dec, 28(6), 487 - 91
Presence of erm genes among macrolide-resistant Gram-positive bacteria isolated from Danish farm soil; Jensen LB et al.; The presence of erm genes was investigated among macrolide-resistant Gram-positive bacteria isolated from soil samples collected from four Danish farms that had been treated with animal waste . Soil samples were collected before, a few days after spread and 1 1/2 months and 5 months later . In 33% (9/27) of these isolates, an erm gene was detected using PCR . Eight isolates were positive for erm(B) and one isolate was positive for erm(C) . No isolates contained erm(A), erm(D) or erm(F) . The positive isolates were identified to genus level . Two erm(B) positive isolates were identified as Enterococcus spp., and the erm(C)-positive isolate as a Streptococcus spp., probably indicating survival from animal waste . The remaining six erm(B) positive isolates all belonged to the Bacillus cereus group . The erm(B) gene has not previously been identified in B . cereus but is frequently found among enterococci . This result could indicate horizontal transfer from bacteria of animal origin to indigenous soil bacteria.

Arch Pediatr, 2002 Nov, 9(11), 1166 - 72
{Pneumococcal meningitis and resistant bacteria}; Floret D; The emergence of resistance has imposed a modification of the protocols for the treatment of Streptococcus pneumoniae (S pneumoniae) bacterial meningitis . Amoxicillin is no longer adapted . As resistance to C3G appeared, a synergistic effect of an association C3G + vancomycine was demonstrated . Thus currently this association should be recommended in any case of meningitis supposedly due to S pneumoniae . The treatment is then modified according to the evolution and the minimal inhibition concentration (MIC) of the bacteria . The strains carrying a high level of resistance to cephalosporin (MIC > or = 4 micrograms ml-1) or tolerant to vancomycine may cause a therapeutic failure despite an increase of the dosage of cephalosporin . Rifampicin, fosfomycine, or imipenem (despite its risk of convulsions), may represent alternative options, as long as we do not have safe quinolones active on resistant strains of S . pneumoniae . Dexamethasone has been formerly implicated in the relapse of pneumococcal meningitis . Furthermore, its use is questionable since no evidence of a therapeutic benefit has been clearly demonstrated . As a consequence of the resistance phenomenon the management of S . pneumoniae meningitis must include particular measures: at least resistance to penicillin must be checked by the oxacilline disk and the MIC to C3G must be measured by E test; aCSF sample should be obtained between 36 and 48 hours following the beginning of the treatment to check its sterilization . All recent studies have shown a similar prognosis of meningitis due to resistant S . pneumoniae as compared to those due to sensitive strains . However, these data should be interpreted with caution since in these studies, pneumococcus resistant to cephalosporin (the real problem) are not separated from those only resistant to penicillin . Furthermore, presently, the incidence of strains highly resistant to cephalosporin is still low . The new conjugated vaccine against pneumococcus should change the situation if its ability to prevent the circulation of resistant strains is confirmed.

Clin Ther, 2002 Nov, 24(11), 1770 - 85
A prospective, randomized, double-blind multicenter comparison of parenteral ertapenem and ceftriaxone for the treatment of hospitalized adults with community-acquired pneumonia; Vetter N et al.; BACKGROUND: Ertapenem is a once-daily parenteral beta-lactam licensed in the United States in November 2001 and in Europe in May 2002 . OBJECTIVE: This study compared the efficacy and safety profiles of ertapenem with those of ceftriaxone for the treatment of hospitalized adult patients with serious community-acquired pneumonia (CAP) requiring parenteral therapy . METHODS: In this prospective, double-blind (with sponsor blinding), multicenter study, adult patients with CAP were stratified by Pneumonia Severity Index (< or = 3 or > 3) and age (< or = 65 or > 65 years) and randomized (2:1) to receive IV or intramuscular (IM) ertapenem 1 g once daily or IV or IM ceftriaxone 1 g once daily . Investigators could switch patients to an oral antimicrobial agent if clinical improvement was shown after at least 3 days of parenteral therapy . RESULTS: A total of 364 patients were randomized to treatment: 239 to the ertapenem group and 125 to the ceftriaxone group . Three patients in the ertapenem group and 2 in the ceftriaxone group did not receive study therapy . Of the treated patients, 77.1% (182/236) of patients in the ertapenem group and 75.6% (93/123) in the ceftriaxone group were clinically evaluable . Among clinically evaluable patients, the mean (SD) durations of parenteral and total (parenteral plus optional oral) therapy were 5.5 (2.6) and 11.5 (2.7) days for ertapenem and 5.6 (2.8) and 11.7 (3.0) days for ceftriaxone, respectively . Streptococcus pneumoniae was the most frequently isolated pathogen in both treatment groups . Cure rates were 92.2% for clinically evaluable patients in the ertapenem group and 93.6% for those in the ceftriaxone group (95% CI for the difference, adjusted for stratum, -8.6 to 5.7), fulfilling the criteria for statistical equivalence . At completion of parenteral therapy, 94.7% of patients in the ertapenem group and 95.8% in the ceftriaxone group showed clinical improvement . Infused vein complications (ertapenem, 3.4% {8/236}; ceftriaxone, 7.3% {9/123}) and elevated transaminase levels (ertapenem, 6.3% {13/207}; ceftriaxone, 7.1% {8/113}) were the most common adverse events in both groups . CONCLUSIONS: In this study of hospitalized adult patients, ertapenem therapy, with an oral switch option, was as effective as ceftriaxone with the same oral switch option for treatment of CAP requiring initial parenteral therapy . The overall safety profiles of the 2 drugs were comparable.

J Gen Appl Microbiol, 1997 Dec, 43(6), 325 - 331
Regulation of lactate dehydrogenase synthesis in a ruminal bacterium, Streptococcus bovis; Asanuma N et al.; Lactate dehydrogenase (LDH) was purified from three strains of Streptococcus bovis, and the gene ldh was cloned and sequenced . The ldh of S . bovis from a goat (TH1) was different from the ldhs of two other strains from cattle (TH2, JB1) in that Asp(220) was substituted for Glu . Northern blot analysis revealed that the LDH-mRNA of S . bovis was approximately 1.0 kbp, which was transcribed in a monocistronic fashion . When cells were grown at pH 6.9 in a batch culture, the level of ldh transcript decreased as the growth phase changed; from exponential growth to the cessation of growth . The level of ldh transcript was higher in cells grown at pH 4.5 than at pH 6.9 . This observation was consistent with the amounts of LDH in cells and the percentages of lactate produced . These results support the hypothesis that S . bovis regulates LDH synthesis at the transcriptional level probably in response to intracellular pH.

J Biol Chem, 2003 Mar 7, 278(10), 7996 - 8005 Epub 2002 Dec 24.
Molecular basis of H2O2 resistance mediated by Streptococcal Dpr . Demonstration of the functional involvement of the putative ferroxidase center by site-directed mutagenesis in Streptococcus suis; Pulliainen AT et al.; H(2)O(2) is an unavoidable cytotoxic by-product of aerobic life . Dpr, a recently discovered member of the Dps protein family, provides a means for catalase-negative bacteria to tolerate H(2)O(2) . Potentially, Dpr could bind free intracellular iron and thus inhibit the Fenton chemistry-catalyzed formation of toxic hydroxyl radicals (H(2)O(2) + Fe(2+) --> (.)OH + (-)OH + Fe(3+)) . We explored the in vivo function of Dpr in the catalase- and NADH peroxidase-negative pig and human pathogen Streptococcus suis . We show that: (i) a Dpr allelic exchange knockout mutant was hypersensitive ( approximately 10(6)-fold) to H(2)O(2), (ii) Dpr incorporated iron in vivo, (iii) a putative ferroxidase center was present in Dpr, (iv) single amino acid substitutions D74A or E78A to the putative ferroxidase center abolished the in vivo iron incorporation, and (v) the H(2)O(2) hypersensitive phenotype was complemented by wild-type Dpr or by a membrane-permeating iron chelator, but not by the site-mutated forms of Dpr . These results demonstrate that the putative ferroxidase center of Dpr is functionally active in iron incorporation and that the H(2)O(2) resistance is mediated by Dpr in vivo by its iron binding activity.

Antimicrob Agents Chemother, 2003 Jan, 47(1), 408 - 12
Flow cytometric assessment of susceptibilities of Streptococcus pyogenes to erythromycin and rokitamycin; Braga PC et al.; The effects of erythromycin (a 14-membered ring macrolide) and rokitamycin (a 16-membered ring macrolide) on the viability of the Streptococcus pyogenes M phenotype were studied by means of flow cytometry and fluorescence microscopy by using a combination of two fluorochromes (syto 9 and propidium iodide) that stains live bacteria green and dead bacteria red . In order to apply the flow cytometry, a bacterial sonication procedure was expressly set up to separate single cells from the long, intralaced S . pyogenes chains of up to 30 to 40 cells that have previously prevented the application of flow cytometry to this type of bacteria . The association of flow cytometry using an appropriate sonication procedure, together with a combination of fluorescent probes, offered the possibility of very quickly investigating the different microbiological effects of rokitamycin at 2 microg/ml, which was active on the S . pyogenes M phenotype, and of erythromycin at doses of up to 32 microg/ml, which was not.

Antimicrob Agents Chemother, 2003 Jan, 47(1), 375 - 7
Synergistic lethal effect of a combination of phage lytic enzymes with different activities on penicillin-sensitive and -resistant Streptococcus pneumoniae strains; Loeffler JM et al.; Pal and Cpl-1, two purified bacteriophage lytic enzymes, were tested for their in vitro activity, alone and in combination, against several serotypes of Streptococcus pneumoniae, including penicillin-resistant strains . The enzymes demonstrated synergism in their ability to cleave the bacterial peptidoglycan and thus may be more efficient for the prevention and elimination of pneumococcal colonization.

Antimicrob Agents Chemother, 2003 Jan, 47(1), 292 - 6
Worldwide antimicrobial susceptibility patterns and pharmacodynamic comparisons of gatifloxacin and levofloxacin against Streptococcus pneumoniae: report from the Antimicrobial Resistance Rate Epidemiology Study Team; Jones RN et al.; The use of fluoroquinolones for the treatment of community-acquired respiratory tract infection is increasing . Since for Streptococcus pneumoniae a ratio of the 24-h area under the concentration-time curve (AUC(24)) for the agent to the MIC (AUC(24)/MIC) greater than 30 for the fraction of unbound drug (f(u)) is the major pharmacokinetic-pharmacodynamic (PK-PD) parameter correlating with bacterial eradication by fluoroquinolones in nonclinical models of infection and in infected patients, the Antimicrobial Resistance Rate Epidemiology Study Team systematically compared the in vitro susceptibility patterns and estimated the probability of attainment of the PK-PD target ratios for gatifloxacin and levofloxacin against pneumococci worldwide . Monte Carlo simulation was used to estimate the probability that gatifloxacin or levofloxacin would achieve an f(u) AUC(24)/MIC ratio of 30 or greater . A total of 10,978 S . pneumoniae isolates collected from 1997 to 2000, each indexed by site of infection and geographic region (North America, Latin America, Europe, and Asia-Pacific), were used to estimate the probability mass functions of the microbiological activities for each region considered in the analysis . f(u) AUC(24) probability distribution functions were estimated by using data that were part of each product's submission accepted by the Food and Drug Administration . A 10,000-patient simulation was performed for each drug-organism-region combination . The percentages of strains susceptible to each drug by region were as follows: for gatifloxacin, North America, 99.6%; Latin America, 99.8%; Europe, 99.9%; and Asia-Pacific, 99.2%; for levofloxacin, North America, 99.6%; Latin America, 99.8%; Europe, 99.8%; and Asia-Pacific, 99.1% . The MIC at which 50% of isolates are inhibited (MIC(50)) and the MIC(90) of each drug by region were as follows: for gatifloxacin, North America, 0.25 and 0.5 mg/liter, respectively; Latin America, 0.25 and 0.5 mg/liter, respectively; Europe, 0.25 and 0.5 mg/liter, respectively; and Asia-Pacific, 0.25 and 0.5 mg/liter, respectively; for levofloxacin, North America, 1 and 2 mg/liter, respectively; Latin America, 1 and 2 mg/liter, respectively; Europe, 1 and 1 mg/liter, respectively; and Asia-Pacific, 1 and 1 mg/liter, respectively . The probabilities of attaining an f(u) AUC(24)/MIC ratio greater than 30 for each drug by region were as follows: for gatifloxacin, North America, 97.6%; Latin America, 98.3%; Europe, 99.1%; and Asia-Pacific, 98.8%; for levofloxacin, North America, 78.9%; Latin America, 84.1%; Europe, 87.1%; and Asia-Pacific, 86.5% . These results for a very large collection of recent clinical strains demonstrate that, globally, gatifloxacin is two- to fourfold more active than levofloxacin against S . pneumoniae and that gatifloxacin has an overall 14.3% higher probability of achieving clinically important PK-PD target ratios than levofloxacin.

Antimicrob Agents Chemother, 2003 Jan, 47(1), 211 - 5
Garenoxacin (BMS-284756) and moxifloxacin in experimental meningitis caused by vancomycin-tolerant pneumococci; Rodriguez-Cerrato V et al.; The emergence of multidrug-resistant strains of Streptococcus pneumoniae drives the development and evaluation of new antipneumococcal agents, especially for the treatment of bacterial meningitis . The aims of the present study were to assess the antibacterial effectiveness of two new quinolones, garenoxacin (BMS; BMS-284756) and moxifloxacin (MOX) in experimental meningitis caused by a vancomycin (VAN)-tolerant S . pneumoniae strain and to compare the results with those obtained by therapy with VAN and ceftriaxone (CRO) in combination . Meningitis was induced in young male New Zealand White rabbits by intracisternal inoculation of a VAN-tolerant pneumococcal strain (strain Tupelo) from a child with meningitis . Sixteen hours after inoculation, therapy was given by intravenous administration of BMS at 20 mg/kg of body weight, followed 5 h later by administration at a dosage of 10 mg/kg (n = 9 animals) or MOX as two doses of 20 mg/kg every 5 h (n = 8 animals) . For comparison, we studied the following groups: (i) animals treated with VAN (20 mg/kg every 5 h, three doses) and CRO (125 mg/kg, one dose) (n = 9), (ii) animals infected with a VAN-tolerant strain but not treated (n = 8), (iii) animals infected with a VAN-tolerant pneumococcus isolated from the nasopharynx of a carrier and treated with BMS (n = 8), and (iv) animals infected with a cephalosporin-resistant type 6B S . pneumoniae strain and treated with BMS (n = 6) . The MICs of penicillin, CRO, VAN, BMS, and MOX for the Tupelo strain were 2, 1, 0.5, 0.06, and 0.03 micro g/ml, respectively . The rates of killing of strain Tupelo (the change in the log(10) number of CFU per milliliter per hour) in cerebrospinal fluid at 5 h were -0.70 +/- 0.35, -0.61 +/- 0.44, and -0.49 +/- 0.36 for BMS, MOX, and VAN-CRO, respectively . Therapy with BMS and MOX was as effective as therapy with VAN-CRO against VAN-tolerant pneumococcal meningitis in rabbits.

Antimicrob Agents Chemother, 2003 Jan, 47(1), 166 - 9
In vitro activities of cethromycin (ABT-773), a new ketolide, against Streptococcus pneumoniae strains that are not susceptible to penicillin or macrolides; Mason EO Jr et al.; Pneumococcal resistance to antimicrobials presents problems to physicians for empirical treatment of acute otitis media (AOM) . Three hundred thirty-three isolates of Streptococcus pneumoniae selected for nonsusceptibility to penicillin (MIC >0.1 microg/ml) from the middle ear (n = 325) or mastoid (n = 8) of children seen between 1994 and 2000 at four children's hospitals in the United States were tested by broth microdilution for susceptibility to nine antibiotics . Using NCCLS 2002 breakpoints, resistance to the following drugs was as indicated: amoxicillin, 1%; azithromycin, 71%; cefprozil, 71%; ceftriaxone, 2%; cefdinir, 98%; erythromycin, 70%; levofloxacin, 0%; and trimethoprim-sulfamethoxazole, 93% . Of the penicillin- and erythromycin-nonsusceptible isolates, 97% were inhibited by cethromycin (ABT-773) and 83% were inhibited by telithromycin at a concentration of <or=0.125 microg/ml . Macrolide resistance among penicillin-nonsusceptible pneumococci increased from 44 to 80% in the 6 years of the study from which the isolates were selected; however, the proportion of isolates with M or MLS(B) phenotypes remained constant over the time period (53 and 18%, respectively) . Prior treatment with a macrolide or clindamycin alone or in combination with a beta-lactam resulted in 94 or 85% of isolates causing infections being macrolide and or clindamycin resistant . No prior individual macrolide (azithromycin, erythromycin, or clarithromycin) resulted in more macrolide resistance or in a more prevalent resistance phenotype . The ketolides appear to be active antimicrobials against penicillin- and macrolide-resistant pneumococci.

Antimicrob Agents Chemother, 2003 Jan, 47(1), 77 - 81
Contribution of the 8-methoxy group to the activity of gatifloxacin against type II topoisomerases of Streptococcus pneumoniae; Kishii R et al.; The inhibitory activities (50% inhibitory concentrations {IC(50)s}) of gatifloxacin and other quinolones against both DNA gyrase and topoisomerase IV of the wild-type Streptococcus pneumoniae IID553 were determined . The IC(50)s of 10 compounds ranged from 4.28 to 582 microg/ml against DNA gyrase and from 1.90 to 35.2 microg/ml against topoisomerase IV . The inhibitory activity against DNA gyrase was more varied than that against topoisomerase IV among fluoroquinolones . The IC(50)s for DNA gyrase of the 8-methoxy quinolones gatifloxacin and AM-1147 were approximately seven times lower than those of their 8-H counterparts AM-1121 and ciprofloxacin, whereas the IC(50)s for topoisomerase IV were 1.5 times lower . Moreover, the IC(50) ratios (IC(50) for DNA gyrase/IC(50) for topoisomerase IV) of gatifloxacin, AM-1147, and moxifloxacin, which possess 8-methoxy groups, were almost the same . The 8-methoxy quinolones showed higher antibacterial activity and less mutant selectivity against IID553 than their 8-H counterparts . These results suggest that the 8-methoxy group enhances both target inhibition, especially for DNA gyrase, leading to potent antipneumococcal activity and dual inhibition against both DNA gyrase and topoisomerase IV in the bacterial cell.

Emerg Infect Dis, 2002 Dec, 8(12), 1487 - 91
Antimicrobial resistance in Streptococcus pneumoniae, Taiwan; Hsueh PR et al.; Taiwan has one of the highest levels of antibiotic-resistant pneumococcus in the world . Pneumococcal isolates not susceptible to penicillin first appeared in Taiwan in 1986; in 1995 an increase in the prevalence of nonsusceptibility to penicillins, extended-spectrum cephalosporins, trimethoprim-sulfamethoxazole, and macrolides as well as multidrug resistance began to be recognized . With the persistence of antibiotic selective pressure, resistance in some antibiotics reached a high plateau (beta-lactam antibiotics) or continued to increase (macrolides), while novel resistance (fluoroquinolones) emerged in the last 3 years . Widespread distribution of some novel resistant 23F and 19F clones (and the international epidemic of 23F clones) contributes further to the rapid increase of resistance . Because Streptococcus pneumoniae is a major pathogen that causes community-acquired lower respiratory tract infections and meningitis in adults and children, antibiotic-resistance in this organism is a serious problem.

J Immunol, 2003 Jan 1, 170(1), 438 - 44
Toll-like receptor 2 participates in mediation of immune response in experimental pneumococcal meningitis; Koedel U et al.; Heterologous expression of Toll-like receptor (TLR)2 and CD14 in Chinese hamster ovary fibroblasts was reported to confer responsiveness to pneumococcal peptidoglycan . The present study characterized the role of TLR2 in the host immune response and clinical course of pneumococcal meningitis . Pneumococcal infection of mice caused a significant increase in brain TLR2 mRNA expression at both 4 and 24 h postchallenge . Mice with a targeted disruption of the TLR2 gene (TLR2-/-) showed a moderate increase in disease severity, as evidenced by an aggravation of meningitis-induced intracranial complications, a more pronounced reduction in body weight and temperature, and a deterioration of motor impairment . These symptoms were associated with significantly higher cerebellar and blood bacterial titers . Brain expression of the complement inhibitor complement receptor-related protein y was significantly higher in infected TLR2-/- than in wild-type mice, while the expression of the meningitis-relevant inflammatory mediators IL-1beta, TNF-alpha, IL-6, macrophage-inflammatory protein (MIP)-2, inducible NO synthase, and C3 was similar in both genotypes . We first ectopically expressed single candidate receptors in HEK293 cells and then applied peritoneal macrophages from mice lacking TLR2 and/or functional TLR4 for further analysis . Overexpression of TLR2 and TLR4/MD-2 conferred activation of NF-kappaB in response to pneumococcal exposure . However, pneumococci-induced TNF-alpha release from peritoneal macrophages of wild-type and TLR2/functional TLR4/double-deficient mice did not differ . Thus, while TLR2 plays a significant role in vivo, yet undefined pattern recognition receptors contribute to the recognition of and initiation of the host immune defense toward Streptococcus pneumoniae infection.

J Immunol, 2003 Jan 1, 170(1), 84 - 90
Impaired antibody response to group B streptococcal type III capsular polysaccharide in C3- and complement receptor 2-deficient mice; Pozdnyakova O et al.; Group B Streptococcus (GBS) is the foremost bacterial cause of serious neonatal infections . Protective immunity to GBS is mediated by specific Abs to the organism's capsular polysaccharide Ags . To examine the role of complement in the humoral immune response to type III GBS capsular polysaccharide (III-PS), mice deficient in C3 or in CD21/CD35 (i.e., complement receptors 1 and 2; CR1/CR2) were immunized with III-PS . Mice deficient in C3 or Cr2 had an impaired primary immune response to III-PS . The defective response was characterized by low IgM levels and the lack of an isotype switch from IgM to IgG Ab production . Compared with wild-type mice, C3- and Cr2-deficient mice exhibited decreased uptake of III-PS by follicular dendritic cells within the germinal centers and impaired localization of III-PS to the marginal zone B cells . Complement-dependent uptake of capsular polysaccharide by marginal zone B cells appears necessary for an effective immune response to III-PS . The normal immune response in wild-type mice may require localization of polysaccharide to marginal zone B cells with subsequent transfer of the Ag to follicular dendritic cells.

Infect Immun, 2003 Jan, 71(1), 474 - 82
Identification of LpeA, a PsaA-like membrane protein that promotes cell entry by Listeria monocytogenes; Reglier-Poupet H et al.; The intracellular life of Listeria monocytogenes starts by a complex process of entry involving several bacterial ligands and eukaryotic receptors . In this work, we identified in silico from the sequence of the genome of L . monocytogenes a previously unknown gene designated lpeA (for lipoprotein promoting entry) encoding a 35-kDa protein homologous to PsaA, a lipoprotein belonging to the LraI family and implicated in the cell adherence of Streptococcus pneumoniae and related species . By constructing a mutant of L . monocytogenes in which lpeA is deleted (lpeA mutant), we show that the PsaA-like protein LpeA is not involved in bacterial adherence but is required for entry of L . monocytogenes in eukaryotic cells . In contrast to wild-type bacteria, mutant bacteria failed to invade the epithelial Caco-2 and hepatocyte TIB73 cell lines, as confirmed by confocal microscopy . The mutant bacteria rapidly penetrated in mouse bone marrow-derived macrophages . Surprisingly, lpeA mutant bacteria survive better in macrophages than do wild-type bacteria . This was correlated with a weak exacerbation of virulence of the lpeA mutant in the mouse . LpeA is therefore a novel invasin favoring the entry of L . monocytogenes into nonprofessional phagocytes but not its invasion of macrophages . This is the first report of a lipoprotein promoting cell invasion of an intracellular pathogen.

Infect Immun, 2003 Jan, 71(1), 218 - 25
Genetic alteration of capsule type but not PspA type affects accessibility of surface-bound complement and surface antigens of Streptococcus pneumoniae; Abeyta M et al.; The Streptococcus pneumoniae capsular polysaccharides and pneumococcal surface protein A (PspA) are major determinants of virulence that are antigenically variable and capable of eliciting protective immune responses . By genetically switching the pspA genes of the capsule type 2 strain D39 and the capsule type 3 strain WU2, we showed that the different abilities of antibody to PspA to protect against these strains was not related to the PspA type expressed . Similarly, the level of specific antibody binding to PspA, other surface antigens, and surface-localized C3b did not depend on the PspA type but instead was correlated with the capsule type . The type 3 strain WU2 and an isogenic derivative of D39 that expresses the type 3 capsule bound nearly identical amounts of antibody to PspA and other surface antigens, and these amounts were less than one-half the amount observed with the type 2 parent strain D39 . Expression of the type 3 capsule in D39 also reduced the amount of C3b deposited and its accessibility to antibody, resulting in a level intermediate between the levels observed with WU2 and D39 . Despite these effects, the capsule type was not the determining factor in anti-PspA-mediated protection, as both D39 and its derivative expressing the type 3 capsule were more resistant to protection than WU2 . The specific combination of PspA and capsule type also did not determine the level of protection . The capsule structure is thus a major determinant in accessibility of surface antigens to antibody, but certain strains appear to express other factors that can influence antibody-mediated protection.

Infect Immun, 2003 Jan, 71(1), 196 - 204
4-1BB (CD137) differentially regulates murine in vivo protein- and polysaccharide-specific immunoglobulin isotype responses to Streptococcus pneumoniae; Wu ZQ et al.; 4-1BB (CD137) is induced on activated CD4(+) and CD8(+) T cells and delivers a costimulatory signal upon binding the 4-1BB ligand (4-1BBL) expressed on antigen-presenting cells . Induction of 4-1BB is dependent on activation via the T-cell receptor (TCR) and possibly CD28 . It was previously demonstrated that both an in vivo protein (pneumococcal surface protein A {PspA})- and polysaccharide (phosphorylcholine {PC} determinant of teichoic acid)-specific immunoglobulin (Ig) isotype response to Streptococcus pneumoniae was dependent on CD4(+) TCRalphabeta(+) T cells and B7-dependent costimulation through CD28 . We thus postulated that 4-1BB costimulation would also play a role in regulating the in vivo anti-PspA and anti-PC response to S . pneumoniae . We demonstrate that mice genetically deficient in 4-1BBL elicit a markedly reduced IgM and IgG anti-PC but normal primary and secondary IgG anti-PspA responses to S . pneumoniae relative to those for wild-type mice . However, injection of an agonistic anti-4-1BB monoclonal antibody (MAb), while having no significant effect on the anti-PC response, strongly inhibits the primary anti-PspA response, the generation of PspA-specific memory, and germinal center formation but does not induce a lasting state of tolerance . In contrast, anti-4-1BB MAb has no effect on the anti-PspA response when injected only at the time of secondary immunization . Delay of the addition of anti-4-1BB leads to progressively less inhibition of the primary response up to day 8 . This inhibition is independent of CD8(+) T cells and is associated with the expansion of CD4(+) T cells with an activated phenotype, which is partly dependent on B7-dependent costimulation . These data are the first to suggest a stimulatory role for endogenous 4-1BB-4-1BBL interactions during a humoral immune response to a pathogen and further underscore significant differences in costimulation requirements for an in vivo protein- versus polysaccharide-specific Ig isotype response to an extracellular bacterium.

Infect Immun, 2003 Jan, 71(1), 132 - 9
The hyaluronic acid capsule of Streptococcus uberis is not required for the development of infection and clinical mastitis; Field TR et al.; The frequency at which the genes responsible for capsule biosynthesis occurred in field isolates of Streptococcus uberis was determined . Of the two genotypes detected (hasABC and hasC), the capsular genotype (hasABC) was more common . This genotype was present at a higher frequency in a population isolated from mastitis cases than in a population isolated from cattle bedding . The virulence of a mutant strain of S . uberis (TRF0-6) that lacked the ability to produce a hyaluronic acid capsule due to an insertion within its single copy of hasA (P . N . Ward, T . R . Field, W . G . F . Ditcham, E . Maguin, and J . A . Leigh, Infect . Immun . 69:392-399, 2001) was compared to that of the capsular parental strain (0140J) . Strains TRF0-6 and 0140J infected all mammary gland quarters following experimental challenge . The wild type and the mutant induced overt signs of disease in four out of four and in six out of eight mammary gland quarters, respectively . Both the wild type and the hasA mutant were resistant to killing by bovine neutrophils following cultivation in bovine milk . The ability to withstand the bactericidal action of neutrophils following growth in milk was therefore independent of the capsule and coincided with the ability of supernatants from such cultures to prevent the bactericidal action of neutrophils . This investigation revealed that, in the absence of the capsule, S . uberis is able to withstand the bactericidal effect of bovine neutrophils and induce mastitis in dairy cows.

Infect Immun, 2003 Jan, 71(1), 75 - 85
Both family 1 and family 2 PspA proteins can inhibit complement deposition and confer virulence to a capsular serotype 3 strain of Streptococcus pneumoniae; Ren B et al.; Pneumococcal surface protein A (PspA), a virulence factor of Streptococcus pneumoniae, is exceptionally diverse, being classified into two major families which are over 50% divergent by sequence analysis . A family 1 PspA from strain WU2 was previously shown to impede the clearance of pneumococci from mouse blood and to interfere with complement deposition on the bacterial surface . To determine whether a family 2 PspA can perform the same role as family 1 PspA, the family 1 PspA (from strain WU2) was replaced with a family 2 PspA (from strain TIGR4) by molecular genetic methods to make an isogenic pair of strains expressing different PspA proteins . Surface binding of lactoferrin and interference with C3 deposition by the two types of PspA proteins were determined by flow cytometry, and virulence was assessed in a mouse bacteremia model . Although the family 2 PspA appeared to bind less human lactoferrin than did the family 1 PspA, both PspA proteins could interfere with complement deposition on the pneumococcal surface and could provide full virulence in the mouse infection model . A mutant form of the family 2 PspA with a deletion within the choline-binding region was also produced . Pneumococci with this mutant PspA failed to bind human lactoferrin even though the PspA was present on the pneumococcal surface . The mutant PspA only partially interfered with complement deposition and moderately attenuated virulence . These results suggest that family 1 and family 2 PspA proteins play similar roles in virulence and that surface accessibility of PspA is important for their function.

Aust N Z J Obstet Gynaecol, 2002 Nov, 42(5), 543 - 4
Is penicillin and/or erythromycin resistance present in clinical isolates of group B streptococcus in our community?
Stylianopoulos A, Kelly N, Garland S.
Traditionally group B streptococcus (GBS) has not exhibited resistance to the antibiotics penicillin and erythromycin . Recently there are reports from North America whereby some GBS isolates have exhibited resistance to erythromycin . There have been no studies reported to date to determine whether this resistance trend is also occurring in the Australian population . Over a period of six months from January to June 1999, 250 GBS isolates were collected at the Royal Women's Hospital, Melbourne . Sensitivity to penicillin, erythromycin and vancomycin was determined by disk diffusion . Any isolates that had reduced zones to penicillin, vancomycin or erythromycin had minimum inhibitory concentrations (MIC) determined . No isolates had reduced susceptibility to penicillin or vancomycin . Of the 250 isolates, seven (2.8%, 95% CI = 1.1-5.6%) had resistant MICs to erythromycin of > 1.0 microg/mL . These preliminary data suggest that penicillin therapy is still an effective first-line antibiotic for intrapartum chemoprophylaxis and that erythromycin resistance is low in our population.

J Antimicrob Chemother, 2003 Jan, 51(1), 83 - 91
Efficacy of liposome-encapsulated ciprofloxacin compared with ciprofloxacin and ceftriaxone in a rat model of pneumococcal pneumonia; Ellbogen MH et al.; Encapsulation of ciprofloxacin in sterically stabilized liposomes results in a prolonged circulation time and improved pharmacokinetics . Liposome-encapsulated ciprofloxacin was compared with conventional ciprofloxacin and ceftriaxone in a rat model of pneumococcal pneumonia . Male Sprague-Dawley rats were infected transtracheally with type 3 Streptococcus pneumoniae and then treated with intravenous ceftriaxone (100 mg/kg), ciprofloxacin (40 or 80 mg/kg) or liposomal ciprofloxacin (40 or 80 mg/kg) administered once or twice daily for 3 days . White blood counts, development of bacteraemia and mortality were measured for 10 days . Antibiotic concentrations in serum, lung lavage fluid and white blood cells recovered from lung lavage fluid were determined . Liposomal ciprofloxacin concentrations were significantly higher in serum and lavage fluid compared with conventional ciprofloxacin, resulting in greater area under the serum concentration-time curve and maximum serum concentration . Despite these higher concentrations, survival rates were similar between groups treated with equivalent doses of liposomal ciprofloxacin versus ciprofloxacin . When antibiotics were given once daily, ceftriaxone was more effective than either form of ciprofloxacin.

Diagn Microbiol Infect Dis, 2002 Nov, 44(3), 265 - 71
Microbiologic effectiveness of time- or concentration-based dosing strategies in Streptococcus pneumoniae; Ibrahim KH et al.; This in vitro study evaluated the pharmacodynamic performance of levofloxacin using different dosing strategies against both a levofloxacin-sensitive (MIC = 1 mg/liter) and -resistant (MIC = 16 mg/liter) strain of Streptococcus pneumoniae . The strain was genotypically characterized by a mutation in gyrA and two mutations in parE; resistance was shown not to be efflux-mediated . The purpose of this study was to determine if simulated levofloxacin dosing strategies focused either on time or concentration would affect microbiologic outcome.Differing peak concentration/MIC ratios (1,2, and 10), T>MIC (3.6,9.6,15.6, and 24 h corresponding to 15, 40, 65, and 100% of the 24-h dosing interval), and AUC/MIC ratios (13-180) were generated by varying dosing strategies.Initial bacterial inocula were decreased by 99.9% in each experiment conducted . Despite the wide variation in exposure levels, in terms of AUC/MIC, Cp-max/MIC, and T>MIC, the kill portions of the bacterial density curves were super-imposable between all permutations of antibiotic exposure . However, there appeared to be an AUC/MIC breakpoint (35-40) defining bacterial regrowth.Over a 10-fold concentration range, levofloxacin appeared to kill S . pneumoniae in a concentration-independent fashion . When given in concentrations suitable to achieve specified pharmacodynamic endpoints (AUC/MIC >/=35), levofloxacin demonstrated the ability to eradicate both a levofloxacin-resistant and levofloxacin-sensitive strain of S . pneumoniae in the in vitro model.






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