Streptococci

Mol Microbiol, 2001 Mar, 39(6), 1651 - 60
The puzzle of zmpB and extensive chain formation, autolysis defect and non-translocation of choline-binding proteins in Streptococcus pneumoniae; Berge M et al.; Choline-binding proteins (CBPs) from Streptococcus pneumoniae are involved in several important processes . Inactivation of zmpB, a gene that encodes a surface-located putative zinc metalloprotease, in a S . pneumoniae serotype 4 strain was recently reported to reveal a composite phenotype, including extensive chain formation, lysis defect and transformation deficiency . This phenotype was associated with the lack of surface expression of several CBPs, including the major autolysin LytA . LytA, normally 36 kDa in size, was reported to form an SDS-resistant 80 kDa complex with CinA . ZmpB was therefore proposed to control translocation of CBPs to the surface, possibly through the proteolytic release of CBPs (and RecA) from CinA . Based on the use of 12 independent mariner insertions in the zmpB gene of the well-characterized R6 laboratory strain, we could not confirm several of these observations . Our zmpB mutants: (i) did not form chains; (ii) lysed normally in the presence of deoxycholate, which indicates the presence of a functional autolysin; (iii) transformed at normal frequency; and (iv) contained bona fide CinA and LytA species . Polymorphism of ZmpB between R6 and the serotype 4 isolate could not account for the discrepancy, as inactivation of zmpB (through replacement by transposon-inactivated zmpB R6 alleles) in the latter strain did not affect separation of daughter cells and autolysis . The conflicting observations could be explained by our finding that the reportedly serotype 4 zmpB 'mutant' differed from its S . pneumoniae parent in lacking capsule and in exhibiting characteristic traits of the Streptococcus viridans group, including resistance to optochin.

Mol Microbiol, 2001 Mar, 39(6), 1610 - 22
Identification of the teichoic acid phosphorylcholine esterase in Streptococcus pneumoniae; Vollmer W et al.; Streptococcus pneumoniae is a major human pathogen and many interactions of this bacterium with its host appear to be mediated, directly or indirectly, by components of the bacterial cell wall, specifically by the phosphorylcholine residues which serve as anchors for surface-located choline-binding proteins and are also recognized by components of the host response, such as the human C-reactive protein, a class of myeloma proteins and PAF receptors . In the present study, we describe the identification of the pneumococcal pce gene encoding for a teichoic acid phosphorylcholine esterase (Pce), an enzymatic activity capable of removing phosphorylcholine residues from the cell wall teichoic acid and lipoteichoic acid . Pce carries an N-terminal signal sequence, contains a C-terminal choline-binding domain with 10 homologous repeating units similar to those found in other pneumococcal surface proteins, and the catalytic (phosphorylcholine esterase) activity is localized on the N-terminal part of the protein . The mature protein was overexpressed in Escherichia coli and purified in a one-step procedure by choline-affinity chromatography and the enzymatic activity was followed using the chromophoric p-nitrophenyl-phosphorylcholine as a model substrate . The product of the enzymatic digestion of 3H-choline-labelled cell walls was shown to be phosphorylcholine . Inactivation of the pce gene in S . pneumoniae strains by insertion-duplication mutagenesis caused a unique change in colony morphology and a striking increase in virulence in the intraperitoneal mouse model . Pce may be a regulatory element involved with the interaction of S . pneumoniae with its human host.

Am J Rhinol, 2001 Jan-Feb, 15(1), 47 - 8
Leukotriene B4 levels in rabbit maxillary sinusitis: limitations of the current model; Hurley DB et al.; Since the late 1980s, the rabbit model for sinusitis has been widely used for experimental studies on sinusitis; however, the clinical relevance of these experimental data has been questioned . To elucidate the role of leukotrienes in the pathogenesis of sinusitis, leukotriene B4 (LTB4) levels were determined in acute Streptococcus pneumoniae sinusitis in this model . The rabbit model for acute maxillary sinusitis was utilized . Briefly, the right maxillary ostium of each New Zealand white rabbit was occluded with cyanoacrylate under general anesthesia . Twenty-four hours after occlusion, the occluded sinus received an inoculation of 10(8) Streptococcus pneumoniae (ATCC 10813) or a sham inoculation of saline alone . Rabbits were then sacrificed one week later, and the maxillary sinus mucosae were harvested . Leukotriene B4 levels were determined by ELISA assay . LTB4 levels in the sinuses inoculated with bacteria tended to be higher; however, statistical analysis did not reveal significant differences between the experimental and control groups . It is possible to reliably assess leukotriene B4 levels in this model of sinusitis . Although the data suggest a trend for elevated LTB4 levels, statistical analysis did not support this conclusion . The study also demonstrated significant limitations in the current rabbit model for sinusitis; that is, the standard human sinus bacterial pathogens are minimally pathogenic in rabbit sinuses and the small size of the sinus limits the material available for assay . Further modifications of the model are necessary . After such adjustments, the role of leukotrienes in sinusitis may be further explored.

Arch Med Res, 2000 Nov-Dec, 31(6), 592 - 8
Clinical outcome of invasive infections in children caused by highly penicillin-resistant Streptococcus pneumoniae compared with infections caused by penicillin-susceptible strains; Gomez-Barreto D et al.; BACKGROUND: In this report based on data from the Institutional Surveillance System during 1994-1998, we document the continuing emergence of drug-resistant Streptococcus pneumoniae strains at the Hospital Infantil de Mexico Federico Gomez in Mexico City . METHODS: We evaluate the clinical course of 49 invasive pneumococcal infection outside the central nervous system (CNS) by a number of factors including the site, severity, and place where the infection was acquired, the underlying health of the patient, and the adequacy of antimicrobial therapy . RESULTS: An underlying illness was present in 21 of 49 (43%) patients, 37 (75%) patients had taken previous antimicrobial therapy, and 25% of the infections were nosocomially acquired . Overall, 25 of 49 (51%) of the pneumococcal strains tested were pencillin-resistant; strains with the highest resistance to penicillin were also resistant to cephalosporins . Twenty-two percent of all strains were considered to be multidrug-resistant . Eleven of 25 penicillin-resistant strains were identified as multidrug-resistant, i.e., to erythromycin, TMP/SMX, and chloramphenicol . Ten serotypes accounted for 88% of the isolates, the most frequent serotypes being 23F, 14, 19V, 6A, and 6B . The overall case-fatality rate was 37% (18 of 49), with most deaths occurring within 3-5 days after antibiotic therapy was initiated . There was no difference in the case fatality rate between children with penicillin-nonsusceptible and penicillin-susceptible pneumococcal infections; instead; case-fatality rate correlated with severity of illness on admission and presence of underlying disease . CONCLUSIONS: Characterizing groups at risk for invasive pneumococcal disease could aid in the development of preventive programs and increase the benefits from wide use of future conjugated vaccines.

Antimicrob Agents Chemother, 2001 Apr, 45(4), 1104 - 8
Multiple mutations modulate the function of dihydrofolate reductase in trimethoprim-resistant Streptococcus pneumoniae; Maskell JP et al.; Trimethoprim resistance in Streptococcus pneumoniae can be conferred by a single amino acid substitution (I100-L) in dihydrofolate reductase (DHFR), but resistant clinical isolates usually carry multiple DHFR mutations . DHFR genes from five trimethoprim-resistant isolates from the United Kingdom were compared to susceptible isolates and used to transform a susceptible control strain (CP1015) . All trimethoprim-resistant isolates and transformants contained the I100-L mutation . The properties of DHFRs from transformants with different combinations of mutations were compared . In a transformant with only the I100-L mutation (R12/T2) and a D92-A mutation also found in the DHFRs of susceptible isolates, the enzyme was much more resistant to trimethoprim inhibition (50% inhibitory concentration {IC50}, 4.2 microM) than was the DHFR from strain CP1015 (IC50, 0.09 microM) . However, Km values indicated a lower affinity for the enzyme's natural substrates (Km for dihydrofolate {DHF}, 3.1 microM for CP1015 and 27.5 microM for R12/T2) and a twofold decrease in the specificity constant . In transformants with additional mutations in the C-terminal portion of the enzyme, Km values for DHF were reduced (9.2 to 15.2 microM), indicating compensation for the lower affinity generated by I100-L . Additional mutations in the N-terminal portion of the enzyme were associated with up to threefold-increased resistance to trimethoprim (IC50 of up to 13.7 microM) . It is postulated that carriage of the mutation M53-I-which, like I100-L, corresponds to a trimethoprim binding site in the Escherichia coli DHFR-is responsible for this increase . This study demonstrates that although the I100-L mutation alone may give rise to trimethoprim resistance, additional mutations serve to enhance resistance and modulate the effects of existing mutations on the affinity of DHFR for its natural substrates.

Antimicrob Agents Chemother, 2001 Apr, 45(4), 1099 - 103
rho is not essential for viability or virulence in Staphylococcus aureus; Washburn RS et al.; We have identified the gene for transcription termination factor Rho in Staphylococcus aureus . Deletion of rho in S . aureus reveals that it is not essential for viability or virulence . We also searched the available bacterial genomic sequences for homologs of Rho and found that it is broadly distributed and highly conserved . Exceptions include Streptococcus pneumoniae, Streptococcus pyogenes, Mycoplasma genitalium, Mycoplasma pneumoniae, Ureaplasma urealyticum, and Synechocystis sp . strain PCC6803, all of which appear not to possess a Rho homolog . Complementation studies indicate that S . aureus Rho possesses the same activity as Escherichia coli Rho and that the Rho inhibitor bicyclomycin is active against S . aureus Rho . Our results explain the lack of activity of bicyclomycin against many gram-positive bacteria and raise the possibility that the essentiality of rho may be the exception rather than the rule.

Antimicrob Agents Chemother, 2001 Apr, 45(4), 1078 - 85
Penicillin pharmacodynamics in four experimental pneumococcal infection models; Erlendsdottir H et al.; Clinical and animal studies indicate that with optimal dosing, penicillin may still be effective against penicillin-nonsusceptible pneumococci (PNSP) . The present study examined whether the same strains of penicillin-susceptible pneumococci (PSP) and PNSP differed in their pharmacodynamic responses to penicillin by using comparable penicillin dosing regimens in four animal models: peritonitis, pneumonia, and thigh infection in mice and tissue cage infection in rabbits . Two multidrug-resistant isolates of Streptococcus pneumoniae type 6B were used, one for which the penicillin MIC was 0.016 microg/ml and the other for which the penicillin MIC was 1.0 microg/ml . Two additional strains of PNSP were studied in the rabbit . The animals were treated with five different penicillin regimens resulting in different maximum concentrations of drugs in serum (C(max)s) and times that the concentrations were greater than the MIC (T(>MIC)s) . The endpoints were bacterial viability counts after 6 h of treatment in the mice and 24 h of treatment in the rabbits . Similar pharmacodynamic effects were observed in all models . In the mouse models bactericidal activity depended on the T(>MIC) and to a lesser extent on the Cmax/MIC and the generation time but not on the area under the concentration-time curve (AUC)/MIC . Maximal bactericidal activities were similar for both PSP and PNSP, being the highest in the peritoneum and blood (approximately 6 log10 CFU/ml), followed by the thigh (approximately 3 log10 CFU/thigh), and being the lowest in the lung (approximately 1 log10 CFU/lung) . In the rabbit model the maximal effect was approximately 6 log10 CFU/ml after 24 h . In the mouse models bactericidal activity became marked when T(>MIC) was > or =65% of the experimental time and C(max) was > or =15 times the MIC, and in the rabbit model bactericidal activity became marked when T(>MIC) was > or =35%, Cmax was > or =5 times the MIC, and the AUC at 24 h/MIC exceeded 25 . By optimization of the Cmax/MIC ratio and T(>MIC), the MIC of penicillin for pneumococci can be used to guide therapy and maximize therapeutic efficacy in nonmeningeal infections caused by PNSP.

Antimicrob Agents Chemother, 2001 Apr, 45(4), 1037 - 42
Need for annual surveillance of antimicrobial resistance in Streptococcus pneumoniae in the United States: 2-year longitudinal analysis; Sahm DF et al.; Although changing patterns in antimicrobial resistance in Streptococcus pneumoniae have prompted several surveillance initiatives in recent years, the frequency with which these studies are needed has not been addressed . To approach this issue, the extent to which resistance patterns change over a 1-year period was examined . In this study we analyzed S . pneumoniae antimicrobial susceptibility results produced in our laboratory with isolates obtained over 2 consecutive years (1997-1998 and 1998-1999) from the same 96 institutions distributed throughout the United States . Comparison of results revealed increases in resistant percentages for all antimicrobial agents studied except vancomycin . For four of the agents tested (penicillin, cefuroxime, trimethoprim-sulfamethoxazole, and levofloxacin), the increases were statistically significant (P < 0.05) . Resistance to the fluoroquinolone remained low in both years (0.1 and 0.6%, respectively); in contrast, resistance to macrolides was consistently greater than 20%, and resistance to trimethoprim-sulfamethoxazole increased from 13.3 to 27.3% . Multidrug resistance, concurrent resistance to three or more antimicrobials of different chemical classes, also increased significantly between years, from 5.9 to 11% . The most prevalent phenotype was resistance to penicillin, azithromycin (representative macrolide), and trimethoprim-sulfamethoxazole . Multidrug-resistant phenotypes that included fluoroquinolone resistance were uncommon; however, two phenotypes that included fluoroquinolone resistance not found in 1997-1998 were encountered in 1998-1999 . This longitudinal surveillance study of resistance in S . pneumoniae revealed that significant changes do occur in just a single year and supports the need for surveillance at least on an annual basis, if not continuously.

J Biomol NMR, 2001 Feb, 19(2), 125 - 39
Refined structure of a flexible heptasaccharide using 1H-13C and 1H-1H NMR residual dipolar couplings in concert with NOE and long range scalar coupling constants; Martin-Pastor M et al.; The heptasaccharide isolated from the cell wall polysaccharide of Streptococcus mitis J22 serves as an important model for the dynamics and conformation of complex polysaccharides, illustrating the nature of flexibility with rigid epitopes joined by flexible hinges . One-bond C-H residual dipolar couplings (1D(CH)) and long-range H-H residual dipolar couplings (nD(HH)) were measured for the heptasaccharide in a cetylpyridinium chloride/hexanol/brine lamellar liquid crystal medium . A method is proposed to determine the nD(HH) in natural abundance based on a 13C resolved 1H TOCSY pulse sequence previously published to determine the homonuclear scalar couplings . Different methods for interpretation of the 1D(CH) and the nD(HH) residual dipolar coupling data obtained were compared and combined with the NOE and long-range H,C and C,C scalar couplings available for this heptasaccharide . A flexible model of the heptasaccharide was determined in which two structurally well-defined regions involving four and two sugar residues, respectively are joined by a flexible hinge which involves two 1-->6 glycosidic linkages.

Arch Inst Pasteur Alger, 1998, 62, 52 - 61
{In vitro activity of trovafloxacin (CP-99,219) against 434 bacterial strains: comparative study with other fluoroquinolones}; Tali-Maamar H et al.; We have evaluated the activity of a new fluoroquinolone, trovafloxacin (CP-99,219), against 434 strains; 24 of them are resistant to ciprofloxacin . Against gram-negative bacteria, trovafloxacin has the same activity as the others fluoroquinolones . Against gram-positive bacteria, this antibiotic agent is very active . (MIC = 0.016 to 0.5 microgram/ml); Streptococcus is the most sensitive species . The ciprofloxacin resistant strains are also resistant to trovafloxacin.

Arch Inst Pasteur Alger, 1998, 62, 13 - 23
{Sensitivity to beta lactams and macrolides of Streptococcus pyogenes isolated at the services from 1994 to 1998}; Nait-Kaci S et al.; The identification and antibiotic sensibility of 188 strains of streptocoques pyogenes had been performed from 1994 to March 1998 . We were interested on active antibiotics against streptocoques pyogenes: beta lactamins (penicillin-ampicillin) and macrolids (erythromycin) . The aim of this study is to reveal resistances and calculate percentages of resistant strains to these antibiotics . The WHO recommend to treat streptococcal sore throat with penicillin, and with erythromycin when there is a proved inhibility to the penicillin . No penicillin resistant streptocoques pyogenes has been found in the world, that concords with our study: all strains (188 sp.) are penicillin sensitive . Macrolids resistant strains of streptocoques pyogenes has been described by a lot of countries with different distributions . In our study global percentage of resistant strains to erythromycin is 24% and 29% for throat specimen.

Ann Intern Med, 2001 Mar 20, 134(6), 509 - 17
Principles of appropriate antibiotic use for acute pharyngitis in adults: background; Cooper RJ et al.; The following principles of appropriate antibiotic use for adults with acute pharyngitis apply to immunocompetent adults without complicated comorbid conditions, such as chronic lung or heart disease, and history of rheumatic fever . They do not apply during known outbreaks of group A streptococcus.1 . Group A beta-hemolytic streptococcus (GABHS) is the causal agent in approximately 10% of adult cases of pharyngitis . The large majority of adults with acute pharyngitis have a self-limited illness, for which supportive care only is needed.2 . Antibiotic treatment of adult pharyngitis benefits only those patients with GABHS infection . All patients with pharyngitis should be offered appropriate doses of analgesics and antipyretics, as well as other supportive care.3 . Limit antibiotic prescriptions to patients who are most likely to have GABHS infection . Clinically screen all adult patients with pharyngitis for the presence of the four Centor criteria: history of fever, tonsillar exudates, no cough, and tender anterior cervical lymphadenopathy (lymphadenitis) . Do not test or treat patients with none or only one of these criteria, since these patients are unlikely to have GABHS infection . For patients with two or more criteria the following strategies are appropriate: a) Test patients with two, three, or four criteria by using a rapid antigen test, and limit antibiotic therapy to patients with positive test results; b) test patients with two or three criteria by using a rapid antigen test, and limit antibiotic therapy to patients with positive test results or patients with four criteria; or c) do not use any diagnostic tests, and limit antibiotic therapy to patients with three or four criteria . 4 . Throat cultures are not recommended for the routine primary evaluation of adults with pharyngitis or for confirmation of negative results on rapid antigen tests when the test sensitivity exceeds 80% . Throat cultures may be indicated as part of investigations of outbreaks of GABHS disease, for monitoring the development and spread of antibiotic resistance, or when such pathogens as gonococcus are being considered.5 . The preferred antibiotic for treatment of acute GABHS pharyngitis is penicillin, or erythromycin in a penicillin-allergic patient.

Ann Intern Med, 2001 Mar 20, 134(6), 479 - 86
Principles of appropriate antibiotic use for treatment of acute respiratory tract infections in adults: background, specific aims, and methods; Gonzales R et al.; The need to decrease excess antibiotic use in ambulatory practice has been fueled by the epidemic increase in antibiotic-resistant Streptococcus pneumoniae . The majority of antibiotics prescribed to adults in ambulatory practice in the United States are for acute sinusitis, acute pharyngitis, acute bronchitis, and nonspecific upper respiratory tract infections (including the common cold) . For each of these conditions-especially colds, nonspecific upper respiratory tract infections, and acute bronchitis (for which routine antibiotic treatment is not recommended)-a large proportion of the antibiotics prescribed are unlikely to provide clinical benefit to patients . Because decreasing community use of antibiotics is an important strategy for combating the increase in community-acquired antibiotic-resistant infections, the Centers for Disease Control and Prevention convened a panel of physicians representing the disciplines of internal medicine, family medicine, emergency medicine, and infectious diseases to develop a series of "Principles of Appropriate Antibiotic Use for Treatment of Acute Respiratory Tract Infections in Adults." These principles provide evidence-based recommendations for evaluation and treatment of adults with acute respiratory illnesses.This paper describes the background and specific aims of and methods used to develop these principles . The goal of the principles is to provide clinicians with practical strategies for limiting antibiotic use to the patients who are most likely to benefit from it . These principles should be used in conjunction with effective patient educational campaigns and enhancements to the health care delivery system that facilitate nonantibiotic treatment of the conditions in question.

Infect Immun, 2001 Apr, 69(4), 2732 - 5
Generation and characterization of a defined mutant of Streptococcus suis lacking suilysin; Allen AG et al.; A defined allelic-replacement mutant of the sly gene, encoding a thiol-activated cytolysin, from a European isolate of Streptococcus suis serotype 2 was generated and characterized . Unlike the parental strain, it is nonhemolytic, noncytotoxic for cultured macrophage-like cells, avirulent in a mouse infection model, yet only slightly attenuated in a porcine model of systemic infection.

Infect Immun, 2001 Apr, 69(4), 2477 - 86
Mosaic genes and mosaic chromosomes: intra- and interspecies genomic variation of Streptococcus pneumoniae; Hakenbeck R et al.; Streptococcus pneumoniae remains a major causative agent of serious human diseases . The worldwide increase of antibiotic resistant strains revealed the importance of horizontal gene transfer in this pathogen, a scenario that results in the modulation of the species-specific gene pool . We investigated genomic variation in 20 S . pneumoniae isolates representing major antibiotic-resistant clones and 10 different capsular serotypes . Variation was scored as decreased hybridization signals visualized on a high-density oligonucleotide array representing 1,968 genes of the type 4 reference strain KNR.7/87 . Up to 10% of the genes appeared altered between individual isolates and the reference strain; variability within clones was below 2.1% . Ten gene clusters covering 160 kb account for half of the variable genes . Most of them are associated with transposases and are assumed to be part of a flexible gene pool within the bacterial population; other variable loci include mosaic genes encoding antibiotic resistance determinants and gene clusters related to bacteriocin production . Genomic comparison between S . pneumoniae and commensal Streptococcus mitis and Streptococcus oralis strains indicates distinct antigenic profiles and suggests a smooth transition between these species, supporting the validity of the microarray system as an epidemiological and diagnostic tool.

Infect Immun, 2001 Apr, 69(4), 2416 - 27
Multilocus sequence typing of Streptococcus pyogenes and the relationships between emm type and clone; Enright MC et al.; Multilocus sequence typing (MLST) is a tool that can be used to study the molecular epidemiology and population genetic structure of microorganisms . A MLST scheme was developed for Streptococcus pyogenes and the nucleotide sequences of internal fragments of seven selected housekeeping loci were obtained for 212 isolates . A total of 100 unique combinations of housekeeping alleles (allelic profiles) were identified . The MLST scheme was highly concordant with several other typing methods . The emm type, corresponding to a locus that is subject to host immune selection, was determined for each isolate; of the >150 distinct emm types identified to date, 78 are represented in this report . For a given emm type, the majority of isolates shared five or more of the seven housekeeping alleles . Stable associations between emm type and MLST were documented by comparing isolates obtained decades apart and/or from different continents . For the 33 emm types for which more than one isolate was examined, only five emm types were present on widely divergent backgrounds, differing at four or more of the housekeeping loci . The findings indicate that the majority of emm types examined define clones or clonal complexes . In addition, an MLST database is made accessible to investigators who seek to characterize other isolates of this species via the internet .

Infect Immun, 2001 Apr, 69(4), 2309 - 17
Essential role for cellular phosphoglucomutase in virulence of type 3 Streptococcus pneumoniae; Hardy GG et al.; Synthesis of the Streptococcus pneumoniae type 3 capsule requires the pathway glucose-6-phosphate (Glc-6-P) --> Glc-1-P --> UDP-Glc --> UDP-glucuronic acid (UDP-GlcUA) --> (GlcUA-Glc)(n) . The UDP-Glc dehydrogenase and synthase necessary for the latter two steps, and essential for capsule production, are encoded by genes (cps3D and cps3S, respectively) located in the type 3 capsule locus . The phosphoglucomutase (PGM) and Glc-1-P uridylyltransferase activities necessary for the first two steps are derived largely through the actions of cellular enzymes . Homologues of these enzymes, encoded by cps3M and cps3U in the type 3 locus, are not required for capsule production . Here, we show that cps3M and cps3U also are not required for mouse virulence . In contrast, nonencapsulated isolates containing defined mutations in cps3D and cps3S were avirulent, as were reduced-capsule isolates containing mutations in pgm . Insertion mutants that lacked PGM activity were avirulent in both immunologically normal (BALB/cByJ) and immunodeficient (CBA/N) mice . In contrast, a mutant (JY1060) with reduced PGM activity was avirulent in the former but had only modestly reduced virulence in the latter . The high virulence in CBA/N mice was not due to the lack of antibodies to phosphocholine but reflected a growth environment distinct from that found in BALB/cByJ mice . The reduced PGM activity of JY1060 resulted in enhanced binding of complement and antibodies to surface antigens . However, decomplementation of BALB/cByJ mice did not enhance the virulence of this mutant . Suppressor mutations, only some of which resulted in increased capsule production, increased the virulence of JY1060 in BALB/cByJ mice . The results suggest that PGM plays a critical role in pneumococcal virulence by affecting multiple cellular pathways.

Infect Immun, 2001 Apr, 69(4), 1994 - 2000
Streptococcus iniae virulence is associated with a distinct genetic profile; Fuller JD et al.; Streptococcus iniae causes meningoencephalitis and death in commercial fish species and has recently been identified as an emerging human pathogen producing fulminant soft tissue infection . As identified by pulsed-field gel electrophoresis (PFGE), strains causing disease in either fish or humans belong to a single clone, whereas isolates from nondiseased fish are genetically diverse . In this study, we used in vivo and in vitro models to examine the pathogenicity of disease-associated isolates . Strains with the clonal (disease-associated) PFGE profile were found to cause significant weight loss and bacteremia in a mouse model of subcutaneous infection . As little as 10(2) CFU of a disease-associated strain was sufficient to establish bacteremia, with higher inocula (10(7)) resulting in increased mortality . In contrast, non-disease-associated (commensal) strains failed to cause bacteremia and weight loss, even at inocula of 10(8) CFU . In addition, disease-associated strains were more resistant to phagocytic clearance in a human whole blood killing assay compared to commensal strains, which were almost entirely eradicated . Disease-associated strains were also cytotoxic to human endothelial cells as measured by lactate dehydrogenase release from host cells . However, both disease-associated and commensal strains adhered to and invaded cultured human epithelial and endothelial cells equally well . While cellular invasion may still contribute to the pathogenesis of invasive S . iniae disease, resistance to phagocytic clearance and direct cytotoxicity appear to be discriminating virulence attributes of the disease-associated clone.

Chirurg, 2001 Feb, 72(2), 168 - 73
{Surgical concepts and results in necrotizing fasciitis}; Heitmann C et al.; INTRODUCTION: Necrotizing fasciitis (NF) is a rapidly progressive soft tissue infection involving primarily the superficial fascia and subcutaneous tissue . The disease is caused by Streptococcus pyogenes or synergistic infection of anaerobic and facultative anaerobic bacteria . Further characteristics are severe, intolerable pain and a mortality of 30-50% . PATIENTS AND METHODS: From January 1996 to January 2000 12 patients underwent treatment for NF . The patients' charts were investigated retrospectively . RESULTS: In 7 patients the bacterial cultures showed a mixed, polymicrobial infection and in 5 cases only Streptococcus pyogenes . The NF was localized at the upper extremity (2), abdomen (3), back (1), hip (2) and lower extremity (4) . The area involved was 8 (4-11)% of the total body surface . The surgical procedures in 12 patients were debridement (60x), local transposition flap (2), free muscle flaps (3), lower leg amputation (1) and split thickness skin graft (3x) . Four patients developed streptococcal toxic shock syndrome and two died . In total there were four deaths with a mortality of 33% . In the "survivor group" the time to diagnosis was 2.8 (1-7) days, the time to radical surgery 3.3 (1-9) days . In the "mortality group" it was 6.8 (3-10) days or 9.3 (6-12) days . CONCLUSION: The prognosis of NF seems to be influenced by the site of the infection, because 4 out of 6 patients with NF of the abdomen, back or hip died, but all patients with NF of the extremities survived . The age of the patient is not a key parameter, because also young and previously healthy people also die from the streptococcal toxic shock syndrome . The interval between diagnosis and radical debridement appears to be the crucial factor in terms of prognosis, since early diagnosis and prompt, radical surgery improves the survival rate.

Rev Panam Salud Publica, 2001 Jan, 9(1), 30 - 4
{Effect of sodium fluoride mouth rinses containing xylitol and sorbitol on the number of Streptococcus mutans from human saliva}; Goncalves NC et al.; The objective of this study was to assess the effect of 0.05% sodium fluoride solutions containing 2.5% or 12.5% xylitol on the number of Streptococcus mutans in the human mouth . Fifty boys between 8 and 16 years of age participated in this double-blind crossover study . Of the original 50 boys, 33 finished the study . Participants were randomly divided into four groups . The following solutions were employed: placebo solution; 0.05% sodium fluoride solution; 0.05% sodium fluoride + 2.5% xylitol + 2% sorbitol; 0.05% sodium fluoride + 12.5% xylitol + 2% sorbitol . Each solution was used for a 28-day period (20 mL/day, twice a day), with a 10-day washout period between solutions . There were no significant differences (P = 0.32) between the two xylitol-containing solutions (2.5% vs . 12.5%) concerning the number of Streptococcus mutans . However, there was a significant difference between these two xylitol-containing solutions and the sodium fluoride and placebo solutions (P < 0.001) . Our results suggest that the 0.05% sodium fluoride solutions containing either 2.5% or 12.5% xylitol caused a significant reduction in the number of Streptococcus mutans.

J Clin Pathol, 2001 Mar, 54(3), 214 - 8
Overwhelming infection in asplenic patients: current best practice preventive measures are not being followed; Waghorn DJ; AIMS: Patients without spleens are at increased risk of overwhelming infection . Recently, greater efforts, including the publication of national guidelines, have been made to improve the management of asplenic individuals . In theory, risks of serious sepsis can be reduced by good advice, immunisation, and antibiotic prophylaxis . In practice, such preventive measures might not be followed or may fail . A study of recent cases of overwhelming postsplenectomy infection (OPSI) was undertaken to examine specific associated factors and to determine whether currently recommended preventive measures are being followed . METHODS: Cases of OPSI were identified and reported mainly by microbiologists across the country using a specifically designed proforma . Data including the nature of the infection and vaccination/ antibiotic prophylaxis history since splenectomy were obtained . RESULTS: Seventy seven cases were reported . The age range varied from 3 months (congenital asplenia) to 87 years . In those who had undergone surgical splenectomy, the time interval between surgery and OPSI varied from 24 days to 65 years . Overall mortality reached 50%, with underlying haematological malignancy associated with the highest death rate . Streptococcus pneumoniae caused approximately 90% episodes . Only 31% individuals had received pneumococcal vaccination before OPSI . Seven of 17 pneumococcal infections in immunised cases could be considered vaccine failures . Few patients had been adequately advised on antibiotic prophylaxis or other measures . CONCLUSIONS: Currently accepted best practice for managing asplenic patients is not being followed . Some OPSI cases may still be preventable but many asplenic individuals remain unrecognised . The compilation of asplenic patient registers might help to implement agreed policies with audit necessary to evaluate compliance . More is needed to ensure optimal management for this cohort of the population.

Arch Gerontol Geriatr, 2001 Feb, 32(1), 45 - 55
Prevalence of potential respiratory pathogens in the mouths of elderly patients and effects of professional oral care; Abe S et al.; To evaluate the effectiveness of professional oral health care in reducing the risk of aspiration pneumonia, we examined the prevalence of potential respiratory pathogens in gargled samples from elderly persons . Samples were obtained from 54 elderly subjects over 65 years of age who required daily nursing care, from 21 healthy elderly subjects over 65 years old, and from 22 healthy young subjects under 30 as controls . The prevalence of possible pathogens was determined by culture and the polymerase chain reaction . The percentages detected in samples of Streptococcus pneumoniae, Staphylococcus species, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans from elderly patients requiring daily nursing care were 63.0, 37.0, 14.8, 5.6 and 66.7, respectively . The numbers of C . albicans cells recovered in samples from elderly subjects were significantly higher than those recovered from the healthy young group (P<0.001) . Elderly patients needing daily care and receiving professional oral health care had lower prevalences and cell numbers of C . albicans than did the elderly patients without such oral care . This study showed that professional oral health care in elderly requiring daily nursing care reduced the cell numbers of potential respiratory pathogens.

Clin Infect Dis, 2001 Mar 15, 32 Suppl 1, S39 - 46
What have we learned from pharmacokinetic and pharmacodynamic theories?
Schentag JJ, Gilliland KK, Paladino JA.
Pharmacokinetic characteristics and pharmacodynamic properties dictate antimicrobial response and, along with natural immune responses, clinical outcomes . As new agents are developed with long half-lives, we will lose the ability to differentiate between concentration-dependent and time-dependent properties . The area under the inhibitory concentration curve (AUIC) defines drug regimens as a ratio of drug exposure to minimum inhibitory concentration (MIC) and allows them to be compared with each other . With AUIC and agents with long half-lives, these comparisons are possible regardless of chemical classification or concentration or time-dependent activity . Historical examples of reduced drug exposure from decreased doses (i.e., cefaclor, clarithromycin, and ciprofloxacin), and thus low AUIC values, directly correlate with drug resistance . In the face of rising MICs (as is occurring worldwide with Streptococcus pneumoniae), close attention to appropriate dosing and concentration above the MIC may delay and potentially even prevent antibiotic resistance . Creating selective pressure on reliable antibiotics by inappropriately reducing their doses will undoubtedly challenge these agents and may destroy entire drug classes with similar mechanisms of action or resistance.

Clin Infect Dis, 2001 Mar 15, 32 Suppl 1, S30 - 2
Comparative in vitro activity of moxifloxacin by E-test against Streptococcus pyogenes; Amabile-Cuevas CF et al.; Macrolides are currently used to treat Streptococcus pyogenes infections where allergy or resistance prevents the use of penicillin . However, growing macrolide resistance is now seen worldwide, with rates of 5%-40% being reported . In this context it is therefore important to have other therapeutic options . The aim of this study was to ascertain the potential role of moxifloxacin, a third-generation fluoroquinolone, in the treatment of infections caused by group A S . pyogenes . The antimicrobial susceptibilities of S . pyogenes isolated from 197 adult patients with pharyngotonsillitis were analyzed by the E-test . Twelve percent of the isolates were resistant to macrolides, and 5% showed diminished susceptibility toward penicillin; none of the strains were resistant to cefotaxime or to moxifloxacin (90% minimum inhibitory concentration, 0.25 microg/mL) . Therefore, moxifloxacin may be a therapeutic option in the management of S . pyogenes infections when penicillin cannot be used or when macrolide resistance may be a local issue . Clinical studies of moxifloxacin in pharyngotonsillitis are warranted.

Clin Infect Dis, 2001 Mar 15, 32 Suppl 1, S22 - 9
Penicillin-resistant streptococcus pneumoniae: review of moxifloxacin activity; Dalhoff A et al.; Streptococcus pneumoniae is a significant pathogen of respiratory tract infections such as pneumonia, sinusitis, meningitis, and acute otitis media . Rising incidences of antimicrobial resistance among pneumococcal strains reported worldwide have led to research into and development of advanced antibacterials with improved gram-positive activity . Moxifloxacin, a new 8-methoxy quinolone, has been tested against a variety of S . pneumoniae strains, including penicillin-sensitive, intermediately resistant to penicillin, and penicillin-resistant strains . We review the preclinical data corroborated by the available clinical experience to demonstrate moxifloxacin's activity against S . pneumoniae strains, irrespective of penicillin susceptibility.

Curr Opin Investig Drugs, 2000 Oct, 1(2), 181 - 7
Linezolid Pharmacia Corp; Barrett JF; Linezolid is an oxazolidinone developed by Pharmacia (formerly Pharmacia & Upjohn) for the treatment of multi-resistant Gram-positive infections {187765,317456} . It binds to ribosomal 50S subunits, most likely within domain V within the 23S rRNA peptidyl transferase and a secondary interaction with the 30S subunit . This results in inhibition of the initiation of protein translation at an early point, which is probably N-formylmethionyl-tRNA {335843} . No direct action on DNA or RNA synthesis has been observed {220169} . Linezolid resistance due to a 23S rRNA mutation may emerge in Enterococci during therapy with this antimicrobial, and may be associated with clinical failure {368652} . Following FDA approval, linezolid was launched in May 2000 {368526,368652} . In April 2000, the FDA approved linezolid injection, tablets and oral suspension for the treatment of patients with infections caused by Gram-positive bacteria . It is indicated for adults in the treatment of nosocomial pneumonia, community-acquired pneumonia (CAP), complicated and uncomplicated skin and skin structure infections and vancomycin-resistant enterococcus (VRE) infections caused by methicillin-resistant Staphylococcus aureus (MRSA), VRE faecium and penicillin-susceptible Streptococcus pneumoniae {363503} . The FDA, however, did not grant Pharmacia indications for linezolid in the treatment of CAP due to either penicillin-resistant S aureus (PRSA) or MRSA . In May 2000, Merrill Lynch predicted sales for 2000 to be US $50 million, rising to US $760 million in 2004 {366910} . In February 2000, P&U predicted that peak sales of the drug had the potential to reach in excess of US $750 million {358429} . In February 1999, Morgan Stanley Dean Witter predicted sales of US $40 million in 2000 rising to US $275 million in 2005 {319855} . In December 1998, Deutsche Bank predicted sales of US $100 million in 2000 rising to US $300 million in 2002 {316769}.

Cornea, 2001 Mar, 20(2), 175 - 8
Bacteriologic and clinical efficacy of ofloxacin 0.3% versus ciprofloxacin 0.3% ophthalmic solutions in the treatment of patients with culture-positive bacterial keratitis; Prajna NV et al.; PURPOSE: To compare the efficacy and safety of ofloxacin 0.3% ophthalmic solution with ciprofloxacin 0.3% ophthalmic solution in patients with culture-positive bacterial keratitis . METHODS: Patients with a microbiologic diagnosis of bacterial keratitis were included in this double-masked, parallel-group study and were randomized to treatment with either ofloxacin 0.3% or ciprofloxacin 0.3% ophthalmic solution . One drop of the study medication was instilled during the daytime according to the following schedule: every half-hour on study day 1, every hour on days 2 through 4, and every 2 hours on days 5 through 21 . Healing, the primary outcome measure, was defined as complete reepithelialization, accompanied by nonprogression of stromal infiltrate for 2 days . Secondary outcome measures included signs and symptoms of infection . Patients were monitored throughout the study period for any adverse events . RESULTS: A total of 217 patients completed the study: 112 were treated with ofloxacin and 105 were treated with ciprofloxacin . Streptococcus pneumoniae was the most commonly encountered pathogen in all patients . Complete corneal reepithelialization occurred in 85% of those treated with ofloxacin and in 77% of those treated with ciprofloxacin (p = 0.32) . The average time to corneal ulcer healing was 13.7 days in those treated with ofloxacin and 14.4 days in those treated with ciprofloxacin . Both treatments were well tolerated with no patient discontinuing the study because of side effects . CONCLUSION: Ofloxacin 0.3% and ciprofloxacin 0.3% ophthalmic solutions are effective and safe in the treatment of patients with culture-positive bacterial keratitis.

FEMS Microbiol Ecol, 2001 Mar, 35(1), 49 - 56
The physiological and genetic diversity of bovine Streptococcus bovis strains(1); Jarvis GN et al.; Laboratory Streptococcus bovis strains and isolates obtained from a steer fed increasing amounts of grain had similar growth characteristics, but they differed in their sensitivity to 2-deoxyglucose (2DG), a non-metabolizable glucose analog . The addition of 2DG decreased both growth rate (0.92+/-0.34 h(-1)) and growth yield (ranging from 25 to 63%), but these differences could not be correlated with diet . However, isolates from a steer fed a 90% grain diet were more prone to 2DG-dependent lysis than those from a hay diet (P<0.001) . All S . bovis laboratory strains and isolates had an identical restriction fragment length polymorphism pattern, when their 16S rDNA was digested with HaeIII and HhaI . However, when genomic BOX elements were amplified, 5-12 bands were observed, and the S . bovis isolates and laboratory strains could be grouped into 13 different BOX types . Strains 26 and 581AXY2 had the same BOX type, but the remaining laboratory strains did not form closely related clusters . Strains JB1 and K27FF4 were most closely related to each other . Most of the fresh isolates (24 out of 30) could be grouped into a single cluster (>90% Dice similarity) . This cluster contained isolates from all three diets, but it did not have any of the laboratory strains . The majority (90%) of the isolates obtained from the hay-fed steer exhibited the same BOX type . Because more BOX types were observed if grain was added to the diet, it appears that ruminal S . bovis diversity may be a diet-dependent phenomenon.

Clin Infect Dis, 2001 Mar 15, 32(6), 972 - 4 Epub 2001 Mar 09.
Penicillin-resistant Streptococcus pneumoniae endocarditis: a case report and review; Siegel M et al.; Streptococcus pneumoniae has been a rare cause of endocarditis in the postantibiotic era . The emergence of antibiotic-resistant Pneumococcus species has been accompanied by isolated reports of penicillin-resistant S . pneumoniae (PRSP) endocarditis . We report a case of bivalvular PRSP endocarditis that was treated with vancomycin and trovafloxacin, and we review the literature on this topic.

Eur J Clin Microbiol Infect Dis, 2001 Jan, 20(1), 61 - 4
Clonal relationships among penicillin-susceptible, multiresistant serotype 6B Streptococcus pneumoniae isolates recovered in Greece and France; Syrogiannopoulos GA et al.; In January 1996 the emergence of penicillin-susceptible, multiresistant serotype 6B Streptococcus pneumoniae isolates resistant to chloramphenicol, tetracycline, erythromycin, clindamycin and trimethoprim-sulfamethoxazole was observed in young carriers in the city of Patras, located in the southwestern region of Greece . Later, a significant spread of pneumococci with this unusual phenotype was noted in carriers living in various other areas of the country . Using restriction fragment length polymorphism of the ribosomal RNA genes, clonal relationships were found between these Greek strains and serotype 6B penicillin-susceptible, multiresistant pneumococci isolated in France between January 1992 and September 1996 . The French and Greek isolates appear to have a common ancestry.

Eur J Clin Microbiol Infect Dis, 2001 Jan, 20(1), 49 - 51
Tricuspid valve endocarditis in adult patients without known predisposing factors; Shimoni Z et al.; Four patients with no known predisposing conditions developed tricuspid valve endocarditis . All patients had community-acquired infection with a rapidly progressive course that was complicated by right heart failure and respiratory insufficiency . Pulmonary involvement was prominent in all cases . The infectious process was due to Staphylococcus aureus in three patients and to Streptococcus intermedius in one patient . Three patients underwent early surgical intervention; the outcome was favourable in all cases . It is clear that tricuspid valve endocarditis can occur in the absence of known predisposing factors, and when Staphylococcus aureus is involved, the course of the disease may be acute and rapidly progressive.

Chin Med J (Engl), 1998 Jul, 111(7), 615 - 8
Experimental study on distribution of serotypes and antimicrobial patterns of group B streptococcus strains; Shen A et al.; OBJECTIVE: To obtain information on the distribution of serotypes and antimicrobial agent susceptibilities to group B streptococcus (GBS) strains isolated in Beijing area from 1991 to 1996 . METHODS: Bacterial isolates of GBS were obtained from vaginal and cervical tract of pregnant and nonpregnant women in Beijing Tian Tan Hospital by culture . A total of 76 GBS strains were identified finally by coagglutination . Serotyping was determined by Standard Lancefield method . Susceptibility to test agents was assessed by determining the minimal inhibitory concentrations (MICs) with agar dilution method that was established by the National Committee for Clinical Laboratory Standards (NCCLS) . RESULTS: Seven serotypes were identified among 76 GBS strains isolates . Types II (33%), III (23%) and I a (16%) were the predominant serotypes in pregnant and nonpregnant women . MICs of penicillin G and ampicillin were < or = 0.06 microgram/ml . MICs of cephazolin, cefuroxime and cefoperozone were 0.003 microgram/ml-0.06 microgram/ml . MICs of erythromycin were 0.003 microgram/ml-0.03 microgram/ml . MICs of gentamycin were 1 microgram/ml-32 micrograms/ml . MICs of amikacin were 4 micrograms/ml- > or = 64 micrograms/ml, nearly 12.8% and 40.4% of the strains were resistant to gentamycin and amikacin, respectively . CONCLUSIONS: Our study provides useful epidemiologic data for preparation of GBS type-specific vaccines which can prevent GBS infections and antimicrobial agents susceptibility patterns in China . Routine reports on GBS susceptibilities by clinical laboratories and continuous surveillance for changes in the susceptibility are of considerable clinical importance.

Presse Med, 2000 Nov 18, 29(35), 1948 - 56
{Piercing and its infectious complications . A public health issue in France}; Guiard-Schmid JB et al.; CHARACTERISTIC FEATURES: Piercing, an act that modifies the body, has progressed considerably in France over the last few years . The population involved has grown and become more diversified . Performed with a solid needle or a catheter, a wide variety of anatomic localizations are concerned, particularly the nose, ears, and navel . The shape of the "rings", generally made of surgical steel, niobium or titanium, varies greatly . Wound healing by epithelialisation can take up to several months . INFECTIOUS RISK: Between 10% and 20% of all piercings lead to a local infection . The most commonly found causal agests are Staphylococcus aureus, group A Streptococcus and Pseudomonas sp . These germs can cause severe life-threatening complications even in common localizations (earlobe) . Viral transmission is another risk (hepatitis B, hepatitis C, hepatitis delta, HIV) . A few cases of fatal fulminant hepatitis have been described immediately after piercing . SAFETY MEASURES: Generally performed under less than desirable sanitary conditions, safety measures are needed for piercing . Among professional "piercers", a certain number have emphasized the need for providing their clients with safer services . The prevention of infection risk should be a priority for all . Work along this line has been done in the United States and Canada . In light of the impact on public health, it is important to rapidly develop guidelines and regulations for piercing in France . Both professional piercers and health care workers should participate in developing these safety measures in order to assure their implementation.

Ophthalmic Res, 2001 Mar-Apr, 33(2), 117 - 20
In vitro susceptibilities to topical antibiotics of bacteria isolated from the surface of clinically symptomatic eyes; Egger SF et al.; BACKGROUND: The permanent change of resistance patterns of bacteria causing ocular infections makes repeat susceptibility testings against the most recent clinical isolates mandatory . The aim of the present study was to assess the in vitro susceptibility of ocular bacterial isolates of clinically symptomatic eyes admitted to the outpatient clinic of the eye department of a large central hospital to commonly used topical antibiotics . METHODS: Ocular isolates (n = 454) were tested for their susceptibility to ofloxacin, ciprofloxacin, norfloxacin, gentamicin, tobramycin, meomycin, bacitracin, erythromycin, tetracycline and chloramphenicol . RESULTS: All three tested fluoroquinolones were found to be very effective against gram-negative organisms but demonstrated some weakness against certain strains of gram-positive germs, in particular coagulase-negative staphylococci and Streptococcus viridans . These germs, however, were very susceptible to bacitracin and chloramphenicol . The relative overall in vitro efficacy was (in decreasing order): chloramphenicol, ciprofloxacin, ofloxacin, norfloxacin, bacitracin, tetracycline, neomycin, erythromycin, tobramycin and gentamicin . CONCLUSION: Chloramphenicol had the highest overall in vitro efficacy, but has potential lethal side effects . The fluoroquinolones were highly effective, especially being superior to the aminoglycosides tested, but no single antibiotic provided 100% coverage against all of the bacterial isolates that were tested .

Chest, 2001 Mar, 119(3), 862 - 6
Systemic antibiotics fail to clear multidrug-resistant Klebsiella from a pediatric ICU; Petros AJ et al.; STUDY OBJECTIVEs: To determine the magnitude of infection rate and antimicrobial resistance in a pediatric ICU (PICU), and to evaluate the efficacy of using broad-spectrum antibiotics . DESIGN: A 3-month, prospective, observational cohort audit . SETTING: A 12-bed tertiary, referral PICU . PATIENTS OR PARTICIPANTS: All children admitted to the PICU for > 72 h . INTERVENTIONS: Surveillance cultures of throat and rectum on admission and once weekly thereafter . MEASUREMENTS AND RESULTS: Of the 150 admissions during the 3-month period, a total of 52 patients (24 girls and 28 boys) requiring mechanical ventilation for a minimum of 3 days were enrolled in the audit . The median age and interquartile range (IQR) was 17 months (IQR, 5.8 to 63); length of stay, 6.5 days (IQR, 4 to 13); ventilation days, 5 (IQR, 3 to 11); pediatric risk of mortality score, 14 (IQR, 9 to 19); and risk of mortality, 0.03 (IQR, 0.014 to 0.087) . Fifteen patients (29%) developed 21 infections, mainly lower-airway infections and septicemias . Of the 52 children, 7 children carried multidrug-resistant bacteria and 3 patients progressed to develop four infections with those resistant bacteria . Of the seven carriers, six patients carried gentamicin-resistant Klebsiella . Methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae and gentamicin-resistant Pseudomonas aeruginosa each were carried by one child . Six of those nine resistant isolates were present in the admission flora . Despite the potent combination of piperacillin/tazobactam and amikacin, three children acquired the multidrug-resistant Klebsiella while in the PICU and became nosocomial carriers . CONCLUSIONS: Only surveillance cultures allow the distinction between import of multidrug-resistance and resistant bacteria acquired while in PICU . In this study, two thirds of the resistant isolates were imported . The introduction of newer potent systemic antibiotic combinations failed to control the endemic reservoir of multidrug-resistant Klebsiella and suggests that such policies have little impact.

Presse Med, 2001 Jan, Spec No 1, 5 - 6, 4
{Pneumococcal antibiotic resistance in 1999 . Results from 19 registries for 1999}; Chomarat M; BETA-LACTAM RESISTANCE: Among the 9956 strains of Streptococcus pneumoniae isolated in adults, 39% had some degree of penicillin resistance (reduced susceptibility), but there were relatively few strains highly resistant to penicillin: 10% . Among the 4422 strains isolated in children, the overall rate of penicillin resistance was higher (51%) with 15% highly resistant strains . For amoxicillin, the rate of reduced susceptibility was 25% while 1.4% were amoxicillin-resistant . For ceftaxime the respective figures were 21% and 0.3% OTHER ANTIBIOTIC FAMILIES: Important reduction in the susceptibility of all strains, more pronounced for peni-R strains, for macrolides, cotrimoxazole, tetracyxine and chloramphenicol . Very rare resistance to rifampicin and intact susceptibility to vancomycin . CHILDREN VERSUS ADULTS: The rate of reduced susceptibility to beta-lactams was higher in children: 31% versus 23% for amoxicillin and 21% versus 14% for cefotaxime . However there were only a few rare strains that were amoxicillin and cefotaxime resistant . Unlike what was observed in adults, there were major differences by site of sampling; strains isolated from purulent middle ear fluid exhibited the strongest resistance.

Oral Microbiol Immunol, 2001 Apr, 16(2), 124 - 8
Altered antigenicity in periodontitis patients and decreased adhesion of Porphyromonas gingivalis by environmental temperature stress; Amano A et al.; Periodontopathogenic bacteria survive various environmental changes during the progression of periodontal disease . Alterations in metabolism and protein expression will have to take place to adapt their physiological functions to environmental stress . We examined the effects of an elevation of 2 degrees C in temperature on the adhesive ability and antigenicity of Porphyromonas gingivalis . Elevation of growth temperature of P . gingivalis from 37 degrees C to 39 degrees C remarkably suppressed the expression of surface filamentous structures, such as fimbriae, as well as the adhesive capacities to salivary components and Streptococcus oralis . Sera of severe periodontitis patients revealed a marked increase in serological activity with 39 degrees C cells than with 37 degrees C cells . The alteration of protein profiles of bacterial surface components by temperature elevation was demonstrated by SDS-PAGE, and their Western blot profiles were also different from those of cells grown at 37 degrees C . Although a uniform trend was not found in the altered patterns, sera from severe periodontitis patients detected more antigenic proteins in cells grown at 39 degrees C than 37 degrees C cells . These observations suggest that P . gingivalis downregulates the expression of fimbriae and alters its adhesive capacity and antigenicity by the temperature stress that could occur during the disease progression.

Oral Microbiol Immunol, 2001 Apr, 16(2), 94 - 9
Inhibitory effect of sorbitol on sugar metabolism of Streptococcus mutans in vitro and on acid production in dental plaque in vivo; Takahashi-Abbe S et al.; This study was conducted to find out whether sorbitol inhibits the sugar metabolism of Streptococcus mutans in vitro and the acid production in dental plaque in vivo . S . mutans NCIB 11723 was anaerobically grown in sorbitol-containing medium . The rate of acid production from sugars was estimated with a pH stat . The rate of acid production from glucose or sucrose was not changed at various concentrations of oxygen . By the addition of sorbitol to sugar, however, the acid production was decreased with increasing levels of oxygen . Intracellular NADH/NAD+ ratio and (dihydroxyacetone-phosphate+glyceraldehyde-phosphate)/3-phosphoglycerate ratio were high whenever the acid production was inhibited by sorbitol . Sorbitol also inhibited the acid production in dental plaque in vivo . These results suggest that the increased NADH/NAD+ ratio during sorbitol metabolism through the inactivation of pyruvate formate-lyase by oxygen inhibited glyceraldehyde-phosphate dehydrogenase and then the acid production of S . mutans and the one in dental plaque.

Rev Neurol (Paris), 2001 Jan, 157(1), 55 - 61
{Neurological manifestation of infectious endocarditis: 14 cases}; Pages M et al.; Fourteen cases of infective endocarditis revealed by neurological manifestations are reported: 8 strokes (one transient ischemic attack, one regressing and 6 completed strokes), 2 intracranial hematomas (one due to ruptured mycotic aneurysm), 2 toxic encephalopathies, one grand mal seizure, one suppurative meningitis . Most of them were native valve endocarditis, and streptococcus was the most frequently responsible bacteria . The outcome was characterized by a high mortality (6 cases) and morbidity (4 cases) . This emphasizes the usefulness of preventing antibiotherapy in patients with known predisposing factors and the necessity for these patients to be admitted in neurological intensive care units.

Vet Microbiol, 2001 Apr 2, 79(3), 209 - 23
In vitro evidence for a bacterial pathogenesis of equine laminitis; Mungall BA et al.; Utilizing an in vitro laminitis explant model, we have investigated how bacterial broth cultures and purified bacterial proteases activate matrix metalloproteinases (MMPs) and alter structural integrity of cultured equine lamellar hoof explants . Four Gram-positive Streptococcus spp . and three Gram-negative bacteria all induced a dose-dependent activation of MMP-2 and MMP-9 and caused lamellar explants to separate . MMP activation was deemed to have occurred if a specific MMP inhibitor, batimastat, blocked MMP activity and prevented lamellar separation . Thermolysin and streptococcal pyrogenic exotoxin B (SpeB) both separated explants dose-dependently but only thermolysin was inhibitable by batimastat or induced MMP activation equivalent to that seen with bacterial broths . Additionally, thermolysin and broth MMP activation appeared to be cell dependent as MMP activation did not occur in isolation.These results suggest the rapid increase in streptococcal species in the caecum and colon observed in parallel with carbohydrate induced equine laminitis may directly cause laminitis via production of exotoxin(s) capable of activating resident MMPs within the lamellar structure . Once activated, these MMPs can degrade key components of the basement membrane (BM) hemidesmosome complex, ultimately separating the BM from the epidermal basal cells resulting in the characteristic laminitis histopathology of hoof lamellae . While many different causative agents have been evaluated in the past, the results of this study provide a unifying aetiological mechanism for the development of carbohydrate induced equine laminitis.

J Dent, 2001 Feb, 29(2), 119 - 22
Inhibition of bacterial and glucan adherence to various light-cured fluoride-releasing restorative materials; Kawai K et al.; OBJECTIVES: This study investigated the potential plaque adhesion properties of various light-cured fluoride-releasing restorative materials by measuring the amount of adhering radiolabeled bacteria and glucan . METHODS: Three resin-modified glass ionomer cements (RMGI) and two polyacid-modified resin composites (compomer) were used in this study . As a control, one light-cured resin composite was added . Disk-shaped specimens were made following the manufacturers' recommendations and the respective surfaces were finished with a 600-grit abrasive paper . Streptococcus sobrinus B13 was selected as a cariogenic bacterial strain . The amount of bacteria and glucan adhered to these specimens were measured after 3, 8 and 24h incubations with radiolabeled cariogenic bacteria and sucrose . RESULTS: After 3 and 8h incubations, the amount of adhered bacteria and glucan was small and there were no significant differences among the restorative materials except in the resin composite . Although after 24h incubation the amounts of adhered bacteria and glucan, significantly increased on the RMGIs and compomers, these were still significantly less than the resin composite except one compomer . Although at 3h no good correlation was found between the contact angles and the amount of bacteria and glucans, the correlation coefficients were high at 8 or 24h . In addition, the coefficients for bacteria were always higher than those for glucan irrespective of the incubation times . CONCLUSIONS: After 24h resin-modified glass ionomer cements and compomers showed significantly smaller amounts of adhered bacteria and glucans compared to resin composite with an exception of glucan adherence on one compomer.

Microbiology, 2001 Mar, 147(Pt 3), 653 - 62
Characterization of a copper-transport operon, copYAZ, from Streptococcus mutans; Vats N et al.; A copper-transport (copYAZ) operon was cloned from the oral bacterium Streptococcus mutans JH1005 . DNA sequencing showed that the operon contained three genes (copY, copA and copZ), which were flanked by a single promoter and a factor-independent terminator . copY encoded a small protein of 147 aa with a heavy-metal-binding motif (CXCX(4)CXC) at the C-terminus . CopY shared extensive homology with other bacterial negative transcriptional regulators . copA encoded a 742 aa protein that shared extensive homology with P-type ATPases . copZ encoded a 67 aa protein that also contained a heavy-metal-binding motif (CXXC) at the N-terminus . Northern blotting showed that a 3.2 kb transcript was produced by Cu2+-induced Strep . mutans cells, suggesting that the genes were synthesized as a polycistronic message . The transcriptional start site of the cop operon was mapped and shown to lie within the inverted repeats of the promoter-operator region . Strep . mutans wild-type cells were resistant to 800 microM Cu2+, whereas cells of a cop knock-out mutant were killed by 200 microM Cu2+ . Complementation of the cop knock-out mutant with the cop operon restored Cu2+ resistance to wild-type level . The wild-type and the mutant did not show any differences in susceptibility to other heavy metals, suggesting that the operon was specific for copper . By using a chloramphenicol acetyltransferase reporter gene fusion, the cop operon was shown to be negatively regulated by CopY and could be derepressed by Cu2+.

J Immunol, 2001 Mar 15, 166(6), 4059 - 64
Mice lacking the multidrug resistance protein 1 are resistant to Streptococcus pneumoniae-induced pneumonia; Schultz MJ et al.; Leukotrienes (LTs) are considered important for antibacterial defense in the lung . Multidrug resistance protein 1 (mrp1) is a transmembrane protein responsible for the cellular extrusion of LTC(4) . To determine the role of mrp1 in host defense against pneumonia, mrp1(-/-) and wild-type mice were intranasally inoculated with Streptococcus pneumoniae . mrp1(-/-) mice displayed a diminished outgrowth of pneumococci in lungs and a strongly reduced mortality . These findings were related to an effect of mrp1 on LT metabolism, because survival was similar in mrp1(-/-) and wild-type mice treated with the 5-lipoxygenase-activating protein inhibitor MK-886 . Although LTC(4) levels remained low in the bronchoalveolar lavage fluid of mrp1(-/-) mice, LTB(4) concentrations were higher than in wild-type mice . These elevated LTB(4) concentrations were important for the relative protection of mrp1(-/-) mice, because the LTB(4) antagonist LTB(4)-dimethyl amide abolished their survival advantage . In vitro experiments suggested that the intracellullar accumulation of LTC(4) in mrp1(-/-) mice results in product inhibition of LTC(4)-synthase, diminishing substrate competition between LTA(4)-hydrolase (which yields LTB(4)) and LTC(4)-synthase for the available LTA(4) . We conclude that mrp1(-/-) mice are resistant against pneumococcal pneumonia by a mechanism that involves increased release of LTB(4) . These results identify mrp1 as a novel target for adjunctive therapy in pneumonia.

Clin Diagn Lab Immunol, 2001 Mar, 8(2), 441 - 5
Human T-cell responses to the glucosyltransferases of Streptococcus mutans; Chia JS et al.; We previously reported differential humoral responses to glucosyltransferases (GTFs), with significantly higher saliva and serum antibody levels to GtfD than to GtfB or GtfC . To test the hypothesis that cellular immune responses to these molecules also may differ, peripheral blood mononuclear cell (PBMC) and T-cell proliferative responses in young adults and children with distinct genetic backgrounds were determined using purified recombinant GtfC and GtfD . PBMCs from all of the volunteers responded to GtfC and -D, but responses were directed predominantly towards GtfD and were major histocompatibility class II antigen dependent . A predominant T-cell response to GtfD, over GtfC, was detectable at various antigen concentrations ranging from 1 to 20 microg/ml and correlated with the differential serum immunoglobulin G (IgG) and salivary IgA antibody responses to the GTFs . Therefore, in naturally sensitized humans, Streptococcus mutans GTFs stimulate differential humoral and cellular immune responses, with the secreted form of GtfD eliciting a stronger response than the cell wall-associated form of GtfC.

Clin Diagn Lab Immunol, 2001 Mar, 8(2), 363 - 9
Are the opsonophagocytic activities of antibodies in infant sera measured by different pneumococcal phagocytosis assays comparable?
Vakevainen M, Jansen W, Saeland E, Jonsdottir I, Snippe H, Verheul A, Kayhty H.
Host protection against Streptococcus pneumoniae is mainly mediated by opsonin-dependent phagocytosis . Several techniques for measuring opsonophagocytic activity (OPA) of antibodies to S . pneumoniae have been standardized and used . These include the viable cell-assay, flow-cytometric assays, and an assay utilizing radiolabeled bacteria . Using these different methods, we measured the OPA of antibodies to S . pneumoniae types 6B and 19F from the sera of infants immunized with a pneumococcal conjugate vaccine, PncCRM . Generally, the results obtained by the various techniques correlated well, although serotype-specific differences were found (6B, r = 0.78 to 0.95, P < 0.001; 19F, r = 0.50 to 0.84, P < 0.001) . The same serotype-specific differences were observed for the relationship between the concentrations of specific immunoglobulin G antibodies measured by enzyme immunoassay and the OPA . Since the sensitivities of the OPA assays differed, the most prominent discrepancies between the techniques were found at low antibody concentrations.

Clin Diagn Lab Immunol, 2001 Mar, 8(2), 251 - 7
Cloning and characterization of the gene encoding the glutamate dehydrogenase of Streptococcus suis serotype 2; Okwumabua O et al.; Given the lack of effective vaccines to control Streptococcus suis infection and the lack of a rapid and reliable molecular diagnostic assay to detect its infection, a polyclonal antibody was raised against the whole-cell protein of S . suis type 2 and used to screen an S . suis gene library in an effort to identify protective antigen(s) and antigens of diagnostic importance . A clone that produced a 45-kDa S . suis-specific protein was identified by Western blotting . Restriction analysis showed that the gene encoding the 45-kDa protein was present on a 1.6-kb pair DraI region on the cloned chromosomal fragment . The nucleotide sequence contained an open reading frame that encoded a polypeptide of 448 amino acid residues with a calculated molecular mass of 48.8 kDa, in close agreement with the size observed on Western blots . A GenBank database search revealed that the derived amino acid sequence is homologous to the sequence of glutamate dehydrogenase (GDH) protein isolated from various sources, including conserved motifs and functional domains typical of the family 1-type hexameric GDH proteins, thus placing it in that family . Because of these similarities, the protein was designated the GDH of S . suis . Hybridization studies showed that the gene is conserved among the S . suis type 2 strains tested . Antiserum raised against the purified recombinant protein was reactive with a protein of the same molecular size as the recombinant protein in S . suis strains, suggesting expression of the gene in all of the isolates and antigenic conservation of the protein . The recombinant protein was reactive with serum from pigs experimentally infected with a virulent strain of S . suis type 2, suggesting that the protein might serve as an antigen of diagnostic importance to detect S . suis infection . Activity staining showed that the S . suis GDH activity is NAD(P)H dependent but, unlike the NAD(P)H-dependent GDH from various other sources, that of S . suis utilizes L-glutamate rather than alpha-ketoglutarate as the substrate . Highly virulent strains of S . suis type 2 could be distinguished from moderately virulent and avirulent strains on the basis of their GDH protein profile following activity staining on a nondenaturing gel . We examined the cellular location of the protein using a whole-cell enzyme-linked immunosorbent assay and an immunogold-labeling technique . Results showed that the S . suis GDH protein is exposed at the surface of intact cells.

Clin Diagn Lab Immunol, 2001 Mar, 8(2), 245 - 50
Comparison of a classical phagocytosis assay and a flow cytometry assay for assessment of the phagocytic capacity of sera from adults vaccinated with a pneumococcal conjugate vaccine; Jansen WT et al.; Antibody- and complement-mediated phagocytosis is the main defense mechanism against Streptococcus pneumoniae . A standardized, easy to perform phagocytosis assay for pneumococci would be a great asset for the evaluation of the potential efficacy of (experimental) pneumococcal vaccines . Such an assay could replace the laborious phagocytosis assay of viable pneumococci (classical killing assay) . Therefore, a newly developed phagocytosis assay based on flow cytometry (flow assay) was compared with the conventional killing assay and enzyme-linked immunosorbent assay (ELISA), using sera obtained from adults pre- and postvaccination with either a bivalent conjugate, a tetravalent conjugate, or the 23-valent polysaccharide vaccine . Highly significant correlations were observed between flow assay phagocytosis titers, killing assay phagocytosis titers, and ELISA antibody titers for serotype 6B and 23F as well . For serotype 19F, strong correlations were only observed between killing assay and ELISA titers . A potential drawback of the flow assay might be the low sensitivity compared with that of the killing assay . The choice of what assay to use, however, will depend on the objectives of the assay . When speed, easy performance, sample throughput, improved worker safety, absence of influence of antibiotics, and absence of false positives are the major criteria, the flow assay is the method of choice . When higher sensitivity is the major requirement, the classical killing assay should be used.

J Infect Dis, 2001 Apr 1, 183(7), 1143 - 6 Epub 2001 Mar 01.
Experimental pneumococcal meningitis in mice: a model of intranasal infection; Zwijnenburg PJ et al.; Effective laboratory animal models of bacterial meningitis are needed to unravel the pathophysiology of this disease . Previous models have failed to simulate human meningitis by using a directly intracerebral route of infection . Hyaluronidase is a virulence factor of Streptococcus pneumoniae . In this study, a novel model of murine meningitis is described . Intranasal administration of S . pneumoniae with hyaluronidase induced meningitis in 50% of inoculated mice, as defined by a positive cerebrospinal fluid (CSF) culture and an inflammatory infiltrate in the meninges . None of the mice inoculated without hyaluronidase developed meningitis . Hyaluronidase was found to facilitate pneumococcal invasion of the bloodstream after colonization of the upper respiratory tract . Meningitis was characterized by pleocytosis of CSF and the induction of proinflammatory cytokines and CXC chemokines in brain tissue . These results indicate that this murine model mimics important features of human disease and allow for the use of this model for studying issues related to the pathophysiology and the treatment of pneumococcal meningitis.

J Infect Dis, 2001 Apr 1, 183(7), 1138 - 42 Epub 2001 Mar 01.
Invasive group B streptococcal disease in Maryland nursing home residents; Henning KJ et al.; Between 1991 and 1995, among 999 nonpregnant adult Maryland residents with group B Streptococcus (GBS) isolated from a normally sterile site, 84 resided in nursing homes (NHs) . The age-adjusted annual incidence of GBS infection (per 100,000 population) among those > or = 65 years old was 72.3 for NH residents and 17.5 for community residents (relative risk, 4.1; P < 0.001) . Thirty-four case patients resided in 11 NHs with > or = 2 cases; 1 NH had 8 case patients within 22 months . Six of 8 case patients from 3 NHs had serotype V GBS . Molecular subtyping of several isolates identified 2 case patients in 1 NH with identical subtype patterns . NH residents have a markedly higher incidence of invasive GBS than do community residents > or = 65 years old and may serve as a target group for immunization when GBS vaccines become available . Further evaluation of intra-NH transmission of GBS is warranted.

J Infect Dis, 2001 Apr 1, 183(7), 1043 - 54 Epub 2001 Mar 01.
Spontaneous mutations in the CsrRS two-component regulatory system of Streptococcus pyogenes result in enhanced virulence in a murine model of skin and soft tissue infection; Engleberg NC et al.; CsrS/CsrR is a 2-component system in Streptococcus pyogenes that negatively regulates hyaluronic capsule and several exotoxins . To detect spontaneous mutations in csrRS, mucoid and large colony variants of M1 strain MGAS166 were isolated from experimental murine skin infections . By use of complementation with a csrRS(+) plasmid, relevant mutations were also detected in 7 of 12 human clinical isolates . The presence of spontaneous mutants in mouse infection was associated with larger, more necrotic lesions . Most spontaneous changes in CsrR resulted from single amino acid substitutions, whereas most csrS mutations were frameshift or nonsense mutations . In 2 instances, IS1548 insertions were found in csrS . Experimental inoculation of mixtures of wild-type (wt) and csrRS(-) bacteria yielded larger, more necrotic lesions than did either strain at twice the inoculum, which suggests that these variants may exhibit pathogenic synergy . Spontaneous emergence of csrRS(-) mutants in vivo enhances the virulence of wt bacteria and increases severity of murine skin infection.

J Infect Dis, 2001 Mar 15, 183(6), 887 - 96 Epub 2001 Feb 21.
Pneumococcal carriage and otitis media induce salivary antibodies to pneumococcal surface adhesin a, pneumolysin, and pneumococcal surface protein a in children; Simell B et al.; Local antibodies probably contribute to defense against Streptococcus pneumoniae . This study examined whether pneumococcal carriage and acute otitis media (AOM) induce mucosal antibodies to potential vaccine candidates pneumococcal surface adhesin A (PsaA), pneumolysin (Ply), and pneumococcal surface protein A (PspA) . IgA to all 3 proteins was detected by EIA in saliva of 329 children at ages 6, 12, 18, and 24 months and of 17 adults . A higher proportion of IgA-positive samples and higher antibody concentrations were seen in children with pneumococci-positive cultures of nasopharyngeal samples or middle ear fluid than in children with all cultures negative for pneumococci . The strong correlation between IgA and the presence of the secretory component suggests that the IgA was secretory . The findings indicate that pneumococcal carriage and AOM induce local production of anti-PsaA, anti-Ply, and anti-PspA antibodies early in life.

Biochem Biophys Res Commun, 2001 Mar 9, 281(4), 957 - 61
Streptococcus mutans lipoteichoic acid-induced apoptosis in cultured dental pulp cells from human deciduous teeth; Wang PL et al.; Herein, we suggest that Streptococcus mutans lipoteichoic acid-induced death of dental pulp cells on human deciduous teeth is caused by apoptosis . We provide evidence for the causal role of apoptosis in this process by demonstrating an increase in the proportion of fragmented DNA in such dental pulp cells, which results in a ladder pattern of DNA fragmentation . Additionally, Streptococcus mutans lipoteichoic acid-induced apoptotic cell death is suppressed by caspase inhibitor . Collectively, these findings suggest that Streptococcus mutans lipoteichoic acids may cause apoptosis in human dental pulp cells, and serve as an important factor in pulpitis .

Paediatr Perinat Epidemiol, 2001 Jan, 15(1), 54 - 60
Fetal and neonatal death from maternally acquired infection; Embleton ND; Northern Region's Perinatal Mortality Survey; Infection is a potentially preventable cause of perinatal mortality but there is only limited epidemiological information on which to develop prophylactic guidelines . The aim of this study was to determine the population incidence of perinatal death from maternally acquired infection and to describe the responsible organisms and antibiotic sensitivities, and also the associated risk factors . Fetal and neonatal deaths from perinatal infection in the former Northern Health Region, United Kingdom, were identified for the years 1981-96 using data held by the Perinatal Mortality Survey, and the obstetric, paediatric and pathology case notes were reviewed . Maternally acquired bacterial infection of the baby was identified as responsible for 60 pre-delivery deaths and 142 post-delivery deaths among babies of 24 or more weeks gestation at birth between 1981 and 1996 . There were 630,206 livebirths and 3,591 registered stillbirths in the survey area during this time . Bacterial infection was also considered the primary cause of death in 64 fetuses where delivery occurred at 20-23 weeks gestation between 1989 and 1996 . Although group B streptococcus was the commonest single organism it was only responsible for 30% of all infectious deaths from 24 weeks gestation onwards . Ampicillin resistance was more common in the second half of the study . Infection remains an important cause of perinatal mortality but responsible organisms and antibiotic sensitivities have changed significantly over time . Although 80% of the post-delivery deaths would have received intrapartum antibiotics if current guidelines had been in place, the choice of antibiotics and identification of risk groups requires careful consideration.

S D J Med, 2001 Feb, 54(2), 65 - 9
Antimicrobial resistance: steps to reduce the problem with emphasis on antibiotic utilization the Rapid City experience; Keegan JM; In summary, as the SHEA/IDSA Joint Committee on Prevention of Antimicrobial Resistance suggested, it should be easier to prevent the acquisition of resistance than to respond after the problem is extensive . We have taken that approach in the measures undertaken and outlined above . Our lower rates of resistant microorganisms are, in part, due to this, but also due to the diligent use of antibiotics by the medical staff-largely in avoiding empiric broad-spectrum antibiotic therapy when not needed . Our formulary is not restrictive but new antibiotics are not added unless there is a proven niche . The most appropriate and effective antibiotic at our hospital for Streptococcus pneumoniae is penicillin, for Streptococcus pyogenes, penicillin, for Staphylococcus aureus, nafcillin, for a severe Escherichia Coli infection, gentamicin, and for Pseudomonas aeurginosa, gentamicin and ceftazidime . Our efforts are to maintain this favorable situation for our patients and clinicians . Additionally, we will continue to explore and implement new avenues of prevention, with an emphasis on optimal antibiotic utilization, toward the goal of protecting our patients and health care workers from resistant bacteria.

Scand J Infect Dis, 2001, 33(1), 41 - 6
Group A streptococcus clones causing repeated epidemics and endemic disease in intravenous drug users; Lechot P et al.; Clones of Group A streptococcus (GAS) may spread epidemically and may be associated with enhanced virulence . Sociodemographic and clinical characteristics, together with bacterial isolates, of 79 patients with GAS infection in the Berne region between January 1993 and February 1997 were analysed retrospectively . Using pulsed-field gel electrophoresis, most strains (71%) were found to belong to one of 12 clones . Clonal strains caused significantly more frequent skin abscesses and more severe invasive disease than non-clonal strains . The largest clone (M serotype 1) occurred endemically in non-IVDU patients and caused severe disease in most . Three clones occurred almost exclusively among IVDUs: an M serotype 11 was associated with severe, endemic disease; the other 2 clones, both of M serotype 25, caused epidemics of needle abscesses . Epidemic and endemic spread of GAS clones among IVDUs may be more frequent than previously assumed.

Ther Umsch, 2001 Feb, 58(2), 87 - 93
{Clinical presentation, diagnosis and management of inflammatory heart diseases in childhood}; Jaeggi ET et al.; Inflammatory disorders which may affect the heart muscle, the endocardium, the pericardium and/or the coronary arteries are rare, but potentially devastating diseases . As the incidence of rheumatic heart disease has decreased, children with congenital heart disease now constitute the primary patient population at risk of infective endocarditis . Streptococcus viridans and Staphylococcus aureus are still the most frequently observed organisms . The majority of children with infective endocarditis can be cured today, but good results depend on early diagnosis and accurate treatment . Myocarditis occurs when the heart muscle is involved in an inflammatory process . Causes are numerous, but most common in children are infections with cocksackie viruses . Approximately two-thirds of children with symptomatic acute myocarditis show complete recovery of impaired ventricular function, 10-20% progress of dilatative cardiomyopathy and about 10% die or require heart transplantation . Kawasaki disease is the most prevalent inflammatory coronary artery disease and the leading cause of acquired heart disease in children . The origin of this acute systemic vasculitis remains unknown . Visible coronary arterial abnormalities develop in approximately 20% of children with untreated Kawasaki syndrome . A single dose of gamma-globulin (2 g/kg over 12 h) given within the first 10 days of onset of illness as early as possible, in addition to aspirin has been shown to reduce the duration of fever, which may reflect the severity of ongoing vasculitis, and to reduce the prevalence of coronary artery anomalies.

Swiss Surg, 2001, 7(1), 25 - 7
Streptococcal toxic shock syndrome revealed by a peritonitis . Case report and review of the literature; Vuilleumier H et al.; Group A streptococcus (GAS) or Streptococcus pyogenes cause a variety of life-threatening infectious complications including necrotizing fasciitis, purpura fulminans and streptococcal toxic shock syndrome (STSS) . Exotoxins that act as superantigens are felt to be responsible for STSS . These exotoxins are highly destructive to skin, muscle and soft tissue . This syndrome has a rapid and fulminant course with frequently fatal outcome . GAS remains sensitive to penicillin but in serious infection a combination of clindamycin and ceftriaxone or meropenemum is recommended . Several studies have shown that mortality was dramatically reduced in STSS patients treated with immunoglobulin G given intravenously (IVIG) . Early recognition of this most rapidly progressive infection and prompt operative debridement are required for successful management . This report presents a female patient at two month post-partum with a peritonitis and multi-organ failure.

Jpn J Antibiot, 2000 Dec, 53(12), 652 - 9
{The frequency of Streptococcus pneumoniae strains and sensitivity surveillance for several antibiotics in Gifu Prefecture}; Ishigo S et al.; The frequency and the antibacterial sensitivity of Streptococcus pneumoniae strains isolated from 6 key hospitals (in 5 areas) and 1 otorhinolaryngology clinic in Gifu Prefecture from February to March, 1999, were investigated with several antibiotics . A total of 128 strains of Streptococcus pneumoniae were isolated throughout the study: 47 strains (36.7%) of penicillin-susceptible S . pneumoniae (PSSP), 51 strains (39.8%) of penicillin-intermediate S . pneumoniae (PISP), and 30 strains (23.4%) of penicillin-resistant S . pneumoniae (PRSP); the resistant bacteria being relatively prominent . In these hospitals, PSSP was isolated by 38.8% in all the key hospitals and by 30% in the otolaryngology clinic with almost no discernible difference . PISP was isolated by 63.3%, higher in the otolaryngology clinic and PRSP by 28.6%, higher in the key hospitals conversely . The MIC90s in PISP and PRSP were determined with the antibiotics . In result, only cefditoren (CDTR) showed favorable antibacterial activities with the MIC90 of 0.78 microgram/ml among penicillins or oral cephems . The MIC90s of carbapenems such as imipenem (IPM), meropenem (MEPM), and panipenem (PAPM) were less than 0.39 microgram/ml; particularly, PAPM showed the highest antibacterial activities . Among new quinolones such as tosufloxacin (TFLX), levofloxacin (LVFX), sparfloxacin (SPFX), and ciprofloxacin (CPFX), TFLX showed the highest antibacterial activities with the MIC90 of 0.39 microgram/ml . Other agents showed very low antibacterial activities as the MIC90s were 25 micrograms/ml in minocycline (MINO) and more than 100 micrograms/ml in clarithromycin (CAM) and clindamycin (CLDM).

Acta Microbiol Immunol Hung, 2001, 48(2), 147 - 50
Group-F streptococcal pleuro-pericarditis in a mesothelioma patient after dental surgery (case report); Berek Z et al.; A 71-year-old mesothelioma patient developed pleuro-pericarditis and pleural empyema . Bacteriological examinations and serological identification proved group F Streptococcus in the pleural fluid . Anamnestic data suggested that the source of infection might have been the oral cavity after dental surgery.

Cardiol Young, 2001 Jan, 11(1), 91 - 3
Replacement of the mitral valve in an infant with group B streptococcal endocarditis; Walker TA et al.; Endocarditis due to group B streptococcus is very rare in infants, and may be associated with significant morbidity and mortality . Review of the literature reveals only a single reported case of an infant with this type of streptococcal endocarditis involving the mitral valve . This infant had underlying congenital heart disease, and died shortly after catheterization . We now report group B streptococcal endocarditis occurring in an infant with a structurally normal heart who was treated successfully by replacement of the mitral valve.

Drugs Aging, 2001, 18(1), 1 - 11
Acute exacerbations of chronic bronchitis: what role for the new fluoroquinolones?
Obaji A, Sethi S.
Acute exacerbations of chronic bronchitis (AECB) are a major cause of morbidity and mortality . Bacterial pathogens are implicated in about half the episodes of AECB . Empirical antibacterials have a significant benefit in AECB; however, several recent developments have considerably complicated antibacterial choice for this condition . New fluoroquinolone antibacterials introduced in the last decade are theoretically well suited for the treatment of AECB, as the in vitro antimicrobial spectrum of these drugs includes all the major pathogens involved . The pharmacokinetic and pharmacodynamic properties of the new fluoroquinolones are superior to many other antibacterials used to treat AECB . In trials, clinical success with the new fluoroquinolones was equivalent and bacteriological success was occasionally superior to nonfluoroquinolone comparators . However, these clinical trials did not assess several potentially important end-points for which the theoretical superiority of the fluoroquinolones may translate into differences in outcome . Rare but serious adverse effects with some of the new fluoroquinolones have shaken the confidence of prescribing physicians in this class of drugs . Emergence of the resistance of Streptococcus pneumoniae to fluoroquinolones has raised concerns about indiscriminate and widespread use of the new agents for trivial infections . Patients with AECB are a heterogeneous population who should be stratified in order to appropriately choose empirical antibacterial therapy . Highly efficacious antibacterial therapy, such as the new fluoroquinolones, is appropriate as a first-line choice for patients who have risk factors for a poor outcome or are in intensive care units . Such selected use of the new fluoroquinolones balances individual benefit with societal concerns of the use of these agents for AECB.

Int J Infect Dis, 2000, 4(4), 214 - 8
Trends in antimicrobial resistance and serotype distribution of blood and cerebrospinal fluid isolates of Streptococcus pneumoniae in South Africa, 1991-1998; Huebner RE et al.; OBJECTIVE: Since 1979, the South African Institute for Medical Research (SAIMR) has served as the national reference center for pneumococcal serotyping and monitoring of antibiotic resistance trends . This study documents trends in antimicrobial resistance in pneumococci isolated from blood or cerebrospinal fluid (CSF) between 1991 and 1998 in South Africa . METHODS: Pneumococcal isolates (n = 7406) from either blood or CSF were sent to the SAIMR reference laboratory for serotyping . The isolates were evaluated for resistance to penicillin, chloramphenicol, tetracycline, erythromycin, clindamycin, and rifampicin . RESULTS: Resistance to one or more antibiotics increased significantly from 19% in 1991 to 1994 to 25% in 1995 to 1998 in all ages, and in children from 32% to 38% (P < 10{-6}) . Although penicillin resistance did not increase in children (28.1% vs . 28.9%), penicillin resistance in all ages increased from 9.6% to 18.0% . Significant increases in resistance to chloramphenicol, tetracycline, erythromycin, and rifampicin also were seen in both groups . Multiple resistance increased significantly, from 2.2% to 3.8% . The proportion of isolates with intermediate or high-level penicillin resistance remained constant during the surveillance period . Erythromycin resistance, predominantly expressed as simultaneous resistance to erythromycin and clindamycin, increased from 1.6% to 2.6% . The percentage of erythromycin-resistant isolates that were resistance to erythromycin alone increased from 10.6% to 28.7%, suggesting the emergence of mefE-mediated resistance . In children 2 years of age and younger, although serogroup 6 remained the most common, there were significant increases in serogroups 19, 18, and 13 . The percentage of the total invasive pneumococcal disease in this population that is caused by serogroups found in the nonavalent pneumococcal conjugate vaccine (serogroups 1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F) increased from 72% to 91% . CONCLUSIONS: Antibiotic resistance in the pneumococcus is increasing in South Africa, although the proportion of strains with high-level penicillin resistance has not increased . New conjugate vaccines may not only decrease the burden of all pneumococcal disease but, in addition, lower the incidence of antibiotic-resistant disease in South Africa.

J Clin Microbiol, 2001 Mar, 39(3), 1187 - 9
Antimicrobial resistance of Streptococcus pneumoniae recovered from outpatients with respiratory tract infections in Germany from 1998 to 1999: results of a national surveillance study; Reinert RR et al.; Clinically significant pneumococcal isolates were prospectively collected from outpatients with respiratory tract infections by 19 different clinical microbiology laboratories in Germany . Resistance rates in a total of 961 isolates were as follows: penicillin, 6.6%; clarithromycin, 10.6%; tetracycline, 13.9%; and levofloxacin, 0.1% . Among 324 isolates from children, pneumococcal serotypes 19F (17.0%), 23F (13.0%), and 6B (11.7%) were the predominant types.

J Clin Microbiol, 2001 Mar, 39(3), 1144 - 7
Novel penicillin-, cephalosporin-, and macrolide-resistant clones of Streptococcus pneumoniae serotypes 23F and 19F in Taiwan which differ from international epidemic clones; Chiou CC et al.; A cluster (14 of 18) of Streptococcus pneumoniae serotype 23F isolates that were resistant to penicillin (PEN), cephalosporin, and macrolide was found in one day care center in Kaohsiung, Taiwan . We analyzed the 18 isolates by pulsed field gel electrophoresis (PFGE) . All but one serotype 23F isolate demonstrated identical PFGE patterns, which were different from the established pattern of the internationally spread Spanish 23F clone . The three strains of serotype 19F also showed a uniform pattern . These data strongly suggest that two novel clones of PEN-, cephalosporin-, and macrolide-resistant S . pneumoniae serotypes 23F and 19F are present in Taiwan.

J Clin Microbiol, 2001 Mar, 39(3), 1021 - 4
Evaluation of a medium (STGG) for transport and optimal recovery of Streptococcus pneumoniae from nasopharyngeal secretions collected during field studies; O'Brien KL et al.; Field studies of Streptococcus pneumoniae (pneumococci) nasopharyngeal (NP) colonization are hampered by the need to directly plate specimens in order to ensure isolate viability . A medium containing skim milk, tryptone, glucose, and glycerin (STGG) has been used to transport and store NP material, but its ability to preserve pneumococci has not been evaluated . Our objective was to qualitatively and semiquantitatively evaluate the ability of STGG to preserve pneumococci in NP secretions . Entwined duplicate calcium alginate NP swab samples were obtained from children . One swab was plated directly onto a gentamicin blood agar plate; the other was placed in STGG . Growth from the directly plated specimen was compared with growth from an STGG aliquot immediately cultured or stored at -70 degrees C for 9 weeks, -20 degrees C for 9 weeks, or 4 degrees C for 5 days . Of 186 specimens, 96 (52%) were positive for pneumococci from the direct plating; 94 (98%) of these were positive from the fresh STGG specimen . Pneumococci were recovered from all 38 positive specimens frozen at -70 degrees C, all 18 positive specimens frozen at -20 degrees C, and 18 of 20 positive specimens stored at 4 degrees C . Recovery of pneumococci after storage of NP material in STGG medium at -70 degrees C is at least as good as that from direct plating . Storage at -20 degrees C is also acceptable . Storage at 4 degrees C for 5 days is not ideal.

Clin Infect Dis, 2001 Mar 1, 32(5), 701 - 7 Epub 2001 Feb 28.
Risk factors for acquisition of levofloxacin-resistant Streptococcus pneumoniae: a case-control study; Ho PL et al.; A case-control study was conducted to identify the risk factors associated with levofloxacin-resistant Streptococcus pneumoniae (LRSP) colonization or infection . Twenty-seven case patients (patients with LRSP) were compared with 54 controls (patients with levofloxacin-susceptible S . pneumoniae) . Risk factors that were significantly associated with LRSP colonization or infection, according to univariate analysis, included an older age (median age, 75 years for case patients versus 72.5 years for controls), residence in a nursing home (odds ratio {OR}, 7.2), history of recent (OR, 4.6) and multiple (OR, 4.4) hospitalizations, prior exposure to fluoroquinolones (OR, 10.6) and beta-lactams (OR, 8.6), presence of chronic obstructive pulmonary disease (COPD; OR, 5.9), and nosocomial origin of the bacteria (OR, 5.7) . Multivariate analysis showed that presence of COPD (OR, 10.3), nosocomial origin of the bacteria (OR, 16.2), residence in a nursing home (OR, 7.4), and exposure to fluoroquinolones (OR, 10.7) were independently associated with LRSP colonization or infection . Thus, a distinct group of patients with COPD is the reservoir of LRSP.

Vaccine, 2001 Feb 28, 19(15-16), 1931 - 9
Immunization with recombinant Streptococcus gordonii expressing tetanus toxin fragment C confers protection from lethal challenge in mice; Medaglini D et al.; Tetanus toxin fragment C (TTFC) was expressed on the surface of the vaccine vector Streptococcus gordonii, a Gram-positive commensal bacterium of the human oral cavity . The immunogenicity of recombinant S . gordonii expressing TTFC was assayed in mice immunized by the parenteral and mucosal routes . High serum TTFC-specific IgG responses were induced in both BALB/c and C57BL/6 mice immunized subcutaneously . A total of 82% of vaccinated BALB/c mice were protected from the lethal challenge with 50 LD(50) of tetanus toxin (TT) and a direct correlation between the serum TTFC-specific IgG concentration and survival time of unprotected animals was observed . Intranasal immunization of BALB/c mice was also effective in inducing TTFC-specific serum IgG and local IgA in lung washes . Furthermore, 38% of animals immunized intranasally were protected from the lethal challenge with 10 LD(50) of TT while all control animals died within 24 h . Analysis of the serum IgG subclasses showed that the IgG1 subclass was predominant after parenteral immunization in BALB/c mice (IgG1/IgG2a ratio congruent with6) while following mucosal immunization a mixed IgG1 and IgG2a pattern (IgG1/IgG2a ratio congruent with1) was observed . These data show that TTFC expressed on the surface of S . gordonii is immunogenic by the subcutaneous and mucosal routes and the immune response induced is capable of conferring protection from the lethal challenge with TT.

Dis Colon Rectum, 2001 Feb, 44(2), 291 - 4
Thoracic empyema associated with recurrent colon cancer: report of a case and review of the literature; Osada T et al.; Many types of infections associated with colorectal cancer have been reported . Here, we describe a rare case of thoracic empyema that was observed during immunotherapy for recurrent colon cancer . Culture of the pleural fluid yielded Streptococcus bovis, which is known to be associated with gastrointestinal lesions, especially colorectal malignancies . The possible correlation between these two clinical entities-empyema and colon cancer-is discussed.

J Burn Care Rehabil, 2001 Jan-Feb, 22(1), 35 - 40
The use of 5% mafenide acetate solution in the postgraft treatment of necrotizing fasciitis; Heinle EC et al.; Twenty-nine patients with necrotizing fasciitis who were treated with 5% mafenide acetate solution (MAS) as an adjunct after grafting were compared with 45 patients treated without MAS . Statistical analysis of differences was obtained through P values by chi2 testing . The MAS+ (M) and MAS- (C) groups were similar in percent skin deficit (M = 7.5%; C = 9.8%), with the extremity being the most common area of infection . Streptococcus was the most common single organism but polymicrobial infections were the most prevalent (M = 48%; C = 58%) . Patients with necrotizing fasciitis treated with MAS had fewer debridements per patient (M = 3.7; C = 5.4), fewer closure procedures (average per patient: M = 1.2; C = 1.73) and a higher percent of first-time closures (83 vs 59%; chi2 = 4.26; P = 0.039) . There is a trend toward a lower mortality rate (3.4 vs 13%; chi2 = 2.00; P = 0.158) . We conclude that MAS is a useful adjunct in necrotizing fasciitis wound care protocols.

Tijdschr Diergeneeskd, 2001 Feb 1, 126(3), 66 - 71
{Streptococcus gallolyticus infections in racing pigeons, a literature review}; van der Toorn F et al.; S . gallolyticus, formerly known as S . bovis is known since 1988 as a facultative pathogen of racing pigeons . Important clinical signs include acute mortality, inability to fly, lameness, weight loss and slimy green diarrhea . A pathognomonic sign at post mortem examination is the presence of well circumscribed areas of necrosis in the pectoral muscle . Furthermore tenosynovitis of the supracoracoid muscle and arthritis of the knee, shoulder and hock can be observed . In one study S . gallolyticus septicaemia was diagnosed in 10% of necropsied pigeons . Since S . gallolyticus was also isolated from nearly 40% of clinical healthy pigeons it is regarded as a facultative pathogen . Various biotypes, serotypes and culture supernatant phenotypes can be distinguished . Supernatant phenotypes are identified on the basis of the presence of either a T1, T2 or T3 protein triplet and the presence or absence of an extracellular A protein . S . gallolyticus strains with A protein are highly virulent, while strains with only T3 or T2 protein are of moderately or low virulence respectively . Fimbriae are only seen in highly virulent and some of the moderately virulent strains . Possible virulence factors include survival in macrophages, adhesion to cells and toxin production . Infection with serotype 1 and 2 induces some degree of protection against re-infection with serotype 1, which offers perspectives for the development of a vaccine . Experimentally ampicillin, doxycycline and erythromycin have shown therapeutic effects . For the treatment of clinical cases the use of ampicillin is advocated, together with hygienic measures, such as the use of grid floors and avoiding overcrowding.

Can J Vet Res, 2001 Jan, 65(1), 68 - 72
Specific detection by PCR of Streptococcus agalactiae in milk; Martinez G et al.; The aim of this study was to develop a simple and specific method for direct detection of Streptococcus agalactiae from cow's milk . The method was based on polymerase chain reaction (PCR) using species-specific and universal primers derived from the 16S rRNA gene . The amplification product was verified by restriction endonuclease digest and sequencing . Specific identification was proven on a collection of 147 S . agalactiae isolates of bovine and human origin . In addition, 17 strains belonging to different bacterial species that potentially can be found in milk samples also tested negative . The PCR developed was used for direct detection of S . agalactiae in milk, using for the first time with gram-positive bacteria the nucleic acid-binding properties of diatomaceous earth . The test, which has high specificity, high sensitivity (100 cfu/mL), and can be carried out in less than 24 h, represents an innovative diagnostic tool for the detection of S . agalactiae in milk.

Nippon Rinsho, 2000 Nov, 58(11), 2249 - 54
{Pneumonia and influenza}; Kawakami K et al.; Pneumonia is more frequent in the elderly and results in higher mortality . Primary viral pneumonia is not so common but important in severe cases . Chest X-ray shows grand-glass appearance or linear shadow in pure viral pneumonia cases . That is sometimes specific and clearly different from consolidation or infiltration with bacterial pneumonia . We can try to decrease pneumonia and influenza mortality, if we prevent influenza infections by vaccination and treat by anti-influenza drugs . Secondary bacterial pneumonias are more common, caused by such as Streptococcus pneumonia, Hemophilus influenzae, Branhamella catarrhalis . Gram staining and the culture of purulent sputum was useful for treatment by antibiotics.

Int J Clin Pract, 2000 Nov, 54(9), 585 - 8
Oral antimicrobial susceptibilities of Streptococcus pyogenes recently isolated in five countries; Bandak SI et al.; Between July 1998 and July 1999 1050 clinical isolates of Streptococcus pyogenes were collected from 11 study centres in five countries . Isolates were shipped to a co-ordinating laboratory for NCCLS specified broth microdilution susceptibility testing for penicillin, cefaclor, azithromycin, clarithromycin, erythromycin and roxithromycin . All 1050 isolates of S . pyogenes tested were susceptible to penicillin (MIC < or = 0.12 microgram/ml) and cefaclor (MIC < or = 0.25 microgram/ml) . Azithromycin, clarithromycin and erythromycin resistance rates were 15.9%, 15.4% and 15.8%, respectively . MIC90S for penicillin, cefaclor, azithromycin, clarithromycin, erythromycin, and roxithromycin were 0.015, 0.12, > 4, 8, > 1 and 16 micrograms/ml, respectively . Macrolide (erythromycin) resistance rates were highest in study centres in Italy (31.0%) and Spain (26.6%) . Lower macrolide resistance rates were identified in study centres in Turkey (4.8%), France (3.8%), and Sweden (3.7%) . In conclusion, the isolates of S . pyogenes tested were universally susceptible to beta-lactam antibiotics such as penicillin and cefaclor, while resistance to macrolides was significant and ranged from 3.2% to 31%.

Infect Dis Obstet Gynecol, 2000, 8(5-6), 220 - 7
Intrauterine infection and spontaneous midgestation abortion: is the spectrum of microorganisms similar to that in preterm labor?
McDonald HM, Chambers HM.
OBJECTIVE: To determine whether microorganisms associated with intrauterine infection and preterm labor play a contributing role in midgestation abortion . METHODS: A 4 year retrospective review of spontaneous midgestation abortions for which autopsy and microbiological cultures of placental and fetal tissue were performed was conducted for a tertiary obstetrics hospital, which included a regional referral service for perinatal and fetal pathology . One hundred twenty-nine spontaneously delivered, nonmacerated, midgestation fetuses or stillbirths (of between 16 and 26 weeks' gestation) and placentas were examined and cultured for aerobic and anaerobic bacteria, yeasts, and genital mycoplasmas . RESULTS: Microorganisms were recovered in 85 (66%) cases (57% placentas, 49% fetuses) . Among the culture positive cases, 81% had histological chorioamnionitis, 28% fetal pneumonitis, 38% clinical signs of infection, and 62% ruptured membranes at the time of miscarriage . These differed significantly from culture-negative cases (44%, 5%, 13%, and 34%, respectively) . Group B streptococcus (GBS) was the most significant pathogen, recovered in 21 cases, 13 as the sole isolate, 94% with chorioamnionitis, and 47% in women with intact membranes . Escherichia coli and Ureaplasma urealyticum (22 and 24 cases, respectively) occurred mostly as mixed infections, with ruptured membranes . GBS, MU urealyticum, and Streptococcus anginosus group were individually associated with chorioamnionitis, Bacteroides/Prevotella and S . anginosus with fetal pneumonitis . The spectrum of microorganisms was similar to that in preterm labor at later gestations; however, GBS appeared to be the most significant pathogen in midgestation miscarriage, especially with intact membranes . CONCLUSIONS: Unsuspected intrauterine infection underlies many spontaneous midgestation abortions . GBS is a key pathogen in this setting.

Pediatr Infect Dis J, 2001 Feb, 20(2), 218 - 9
Dichloroacetate treatment for severe refractory metabolic acidosis during neonatal sepsis; Arnon S et al.; We describe a preterm neonate with documented group B Streptococcus sepsis and associated metabolic acidosis whose lactic acidemia was refractory to conventional sodium bicarbonate therapy but responded well to dichloroacetate treatment.

Epidemiol Infect, 2000 Dec, 125(3), 573 - 81
The prevalence and clonal diversity of penicillin-resistant Streptococcus pneumoniae in Kuwait; Ahmed K et al.; Penicillin-resistant Streptococcus pneumoniae (PRSP) is widespread all over the world, including countries previously free of PRSP . This study was undertaken to determine the prevalence, the common serotypes and the clonality of PRSP isolated over a period of 1 year, from various clinical samples from three major hospitals in Kuwait . Strains were identified by standard methods and their antibiotic susceptibility was determined by the agar dilution method . The clonality of the isolates was determined by repetitive extragenic palindromic sequence polymerase chain reaction (REP-PCR) genomic profiling and pulsed field gel electrophoresis (PFGE) . Serotyping was done by Quellung reaction using specific antisera . We found that 55% of the S . pnuemoniae were resistant to penicillin (46% and 9% exhibited intermediate and full resistance, respectively) . Nearly 41% were resistant to sulfamethoxazole-trimethoprim, 9% to cefotaxime and ceftriaxone, 15% to amoxycillin-clavulanate, 17% to cefuroxime, 77 % to cefaclor, and 14% to clindamycin . The commonest serotypes among the PRSPs were 6A, 6B, 14, 19F, 23F and nontypable . PFGE and REP-PCR patterns showed a large diversity of genetic clones of the PRSP . Serotypes 6B, 14, 19F and 23F were more clonally related than the others . Our data showed that the prevalence of PRSP was high, the serotypes were diversified and different genetic clones make up the population of circulating PRSP in Kuwait.

Bull World Health Organ, 2001, 79(1), 43 - 7 Epub 2003 Nov 05.
Comparison of different culture media and storage temperatures for the long-term preservation of Streptococcus pneumoniae in the tropics; Siberry G et al.; OBJECTIVE: The preservation of Streptococcus pneumoniae by standard freezing methods for subsequent tests--such as serotyping and antibiotic susceptibility--is not possible or is difficult in many developing countries because of the high cost of equipment, inadequate equipment maintenance, and irregular power supply . We evaluated alternative low-cost methods, by comparing different culture media and storage temperatures . METHODS: Clinical isolates of five capsular types (1, 5, 7, 19, and 23) of S . pneumoniae were preserved in rabbit blood, sheep blood, skimmed milk, or glycerol-chocolate broth, and stored at -20 degrees C or -70 degrees C . The cultures were also preserved by lyophilization or sand desiccation, followed by storage at room temperature and 4 degrees C . The viability of the preserved cultures was determined by making serial colony counts on day 0 and after 1 week, 4 weeks, 4 months and 16 months . The viability of cultures preserved by sand desiccation and storage at 4 degrees C was also determined every 6 months for up to 68 months . FINDINGS: Irrespective of the media used, cultures maintained at -20 degrees C became nonviable by the fourth month, while those maintained at -70 degrees C were still viable at 16 months . Cultures preserved by lyophilization or sand desiccation lost their viability by the fourth month when maintained at local room temperature (30-42 degrees C), but remained viable when stored at 4 degrees C for up to 68 months . CONCLUSIONS: Our results confirm that freezing at -70 degrees C, or lyophilization and storage at 4 degrees C are the ideal methods for the preservation of S . pneumoniae . In laboratories where lyophilization is not feasible, sand desiccation and storage at 4 degrees C offers an alternative low-cost method for the long-term preservation of S . pneumoniae.

Indian J Exp Biol, 2000 Jul, 38(7), 681 - 6
Comparative chemotherapeutic efficacy of balhimycin, desgluco-balhimycin against experimental MSSA and MRSA infection in mice; Chatterjee DK et al.; Balhimycin and desglucobalhimycin are glycopeptide antibiotics isolated from an Amycolatopsis spp during the search for novel antibacterials against MRSA from the natural product screening at the Research Centre of formerly Hoechst India Ltd . in Bombay, India . Both compounds show excellent in vitro activity against methicillin sensitive and resistant Staphylococcus aureus (MSSA, MRSA) . Both compounds were also found to be active against a number of MRSA strain in the animal studies . The activities were comparable to that of the reference glycopeptides vancomycin and teicoplanin used in these studies . Teicoplanin displayed better in vivo efficacy against S . epidermidis 4929H and Streptococcus pyogenes A77 than either vancomycin or desgluco-balhimycin in the present study . Preliminary studies on pharmacokinetic and acute toxicity were done to get some idea at the early stage of the investigation about the promise of the compounds for development.

Dev Biol (Basel), 2000, 103, 27 - 34
Quantification of C-polysaccharide in Streptococcus pneumoniae polysaccharides by high-performance anion-exchange chromatography with pulsed amperometric detection; Talaga P et al.; A sensitive method, using high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) has been developed for measurement of the C-polysaccharide contamination in Streptococcus pneumoniae capsular polysaccharides, which are part of the polysaccharides based vaccines for the prevention of pneumococcal infections . This method, based on the quantification by HPAEC-PAD of the ribitol released by aqueous hydrofluoric acid (HF) followed by trifluoro acid hydrolysis (TFA) of the pneumococcal polysaccharides is simple and provides both a qualitative and quantitative method for control of the polysaccharides.

J Med Liban, 2000 Jul-Aug, 48(4), 208 - 14
Common bacteria whose susceptibility to antimicrobials is no longer predictable; Snyder JW et al.; The widespread use of antibiotics has been responsible for the development of numerous problems including the emergence of multidrug resistant bacteria, increased number of nosocomial- and community-acquired infections, less than optimal patient outcome, and increased health care costs . Of equal concern is the emergence of resistance in clinical isolates to antibiotics that were once considered "standard" with predictable in vitro susceptibility patterns . Such resistance has been especially notable in organisms that are commonly encountered in a variety of infections including, Streptococcus pneumoniae, Staphylococcus aureus . Enterococci, Klebsiella pneumoniae, and Escherichia coli . It is important for the clinical microbiology laboratory to provide the practicing clinician with accurate and timely antimicrobial susceptibility information which requires the application of standardized and approved in vitro testing methods . The laboratory also serves as a sentinel by maintaining an active monitoring and surveillance program in which current in vitro susceptibility patterns can be compared with local, regional, and national data bases.

Boll Chim Farm, 2000 Nov-Dec, 139(6), 276 - 80
Investigation of antimicrobial activity of essential oils of several Macedonian Thymus L . species (Lamiaceae); Kulevanova S et al.; Antimicrobial activity of twenty specimens of essential oils of eleven Thymus species, naturally occurring in the Macedonian flora, was investigated by agar diffusion and broth dilution methods . Inhibition of growth and microbicidal action was examined on three Gram positive bacteria (Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae) . In spite of wide variability in essential oil composition, ranging from traces of thymol to the amount of about 50% thymol in oils, all examined samples of Thymus essential oil possessed strong antibacterial activity . Zones of inhibition of growth (for 25% dilution of oils) was from 10-54 mm in diameters . MICs ranging from 0.012-0.1% while MMCs were from 0.025-0.4% for essential oils that contained large amounts of phenols and 0.2-1.6% for those which contained traces of phenols and large amounts of geraniol, linalool and (Z + E)-citral.

Bull Tokyo Dent Coll, 2000 Aug, 41(3), 123 - 6
Adsorption of oral bacteria to porous type calcium carbonate; Yamanaka A et al.; The purpose of this study was to investigate the adsorption of {3H}-thymidine labeled oral microorganisms to porous type calcium carbonate (PCC) beads in a buffer containing human parotid saliva and to PCC combined chewing gum sheets . Adsorption rates of Streptococcus sobrinus B13 and 6715, Streptococcus mutans MT8148R and Actinomyces naeslundii T14V with PCC were significantly higher than those with calcium carbonate (CC) beads (p < 0.01) . Adsorption rates of S . sobrinus, S . mutans and A . naeslundii with PCC combined chewing gum were significantly higher than those with CC combined chewing gum (p < 0.01) . The present results suggested that the chewing gum containing PCC may be able to exclude oral bacteria, including cariogenic and periodontopathic bacteria, for prevention of dental caries and periodontal disease.

Am J Vet Res, 2001 Feb, 62(2), 174 - 7
Prevalence of Streptococcus iniae in tilapia, hybrid striped bass, and channel catfish on commercial fish farms in the United States; Shoemaker CA et al.; OBJECTIVE: To determine the prevalence of Streptococcus iniae in tilapia (Oreochromis spp), hybrid striped bass (Morone chrysops X M saxatilis), and channel catfish (Ictalurus punctatus) on commercial fish farms in the United States . ANIMALS: 1,543 fish (970 tilapia, 415 hybrid striped bass, and 158 channel catfish) . PROCEDURES: The dry-swab technique was used for collection of specimens for streptococcal isolation . Specimens were shipped by overnight delivery and processed by use of standard bacteriologic techniques . RESULTS: Streptococcus iniae was not isolated from market-size channel catfish . Prevalence in tilapia and hybrid striped bass was 37 of 970 (3.81%) and 30 of 415 (7.23%), respectively . Prevalence by farm ranged from 0.0 to 27.4% for tilapia and 0.0 to 21.6% for hybrid striped bass . In tilapia, prevalence was lowest in market-size and nursery fish (4 of 239 {1.67%} and 3 of 339 {0.88%}, respectively), with an increase in prevalence for fish in the grow-out stage (30 of 337 {7.96%}) . For hybrid striped bass, prevalence was lowest in nursery and market-size fish (3 of 96 {3.12%} and 1 of 47 {2.12%}, respectively) and highest in fish in the grow-out stage (26 of 272 {9.56%}) . Prevalence in market-size tilapia and hybrid striped bass was 5 of 286 (1.75%) . CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study do not support the contention that S iniae is a serious public health threat associated with commercially raised fish; rather, it represents a limited risk for older or immunocompromised people who incur puncture wounds while handling and preparing fish.

Am J Vet Res, 2001 Feb, 62(2), 171 - 3
Comparison of number of Streptococcus uberis calculated on a volume or weight basis in sand and sawdust bedding; Gabler MT et al.; OBJECTIVE: To determine a method for comparing counts of Streptococcus uberis in sand and sawdust and account for the influence of weight or volume of the bedding material . SAMPLE POPULATION: 2 sources of kiln-dried sawdust and 2 sources of washed sand . PROCEDURES: Sterilized bedding material (100 ml) was weighed and uniformly distributed in an aluminum pan . Each sterilized bedding material was inoculated with a mean of 3.6 X 10(6) (experiment 1) or 2.4 X 10(7) (experiment 2) colony-forming units (CFU) of S uberis/ml of bedding material . Without allowing time for replication of S uberis, inoculated bedding materials were washed with sterile saline (0.9% NaCl) solution . A 200-ml aliquot of wash solution was serially diluted up to 2,500 times with additional saline solution and inoculated on plates containing tryptose agar with 5% sheep blood . After incubation for 48 hours, number of CFU of S uberis was counted . This procedure was replicated 19 and 16 times for each bedding material in experiments 1 and 2, respectively . RESULTS: Evaluation of Bonferroni 95% confidence intervals revealed significant differences for counts of S uberis calculated on a weight basis between sand and sawdust . CONCLUSIONS AND CLINICAL RELEVANCE: Comparison of counts of S uberis determined on a volume basis for sand and sawdust accentuates to a lesser degree the weight difference of the bedding materials and ensures a more appropriate comparison of number of S uberis.

APMIS, 2000 Nov, 108(11), 734 - 8
Comparison of nasal swab culture, quantitative culture of nasal mucosal tissue and PCR in detecting Streptococcus pneumoniae carriage in rats; Kontiokari T et al.; It is not known how well nasopharyngeal swab culture represents pneumococcal carriage status . We tested this by comparing swab culture to quantitative culture and quantitative PCR of mucosal tissue in a rat model of pneumococcal carriage . Quantitative culture and quantitative PCR identified significantly more carriers compared to swab culture (differences 15% and 33%, 95% CI 1-28% and 16-47%, p=0.04 and 0.001, respectively) . The sensitivity and specificity of swab culture was 75/92% and 63/100% compared to quantitative tissue culture and quantitative PCR, respectively . The quantitative estimates of culture and PCR were very similar (Pearson correlation coefficient 0.79, p<0.001) . In conclusion, even a well-controlled swab sampling markedly underestimates pneumococcal carriage rate, and simultaneous use of quantitative culture and PCR increases the number of positive samples by about one third.

APMIS, 2000 Nov, 108(11), 729 - 33
Buffy coat PCR for diagnosis of experimental pneumococcal pneumonia; Ng W et al.; An immunocompetent murine model of pneumococcal pneumonia and bacteremia was used to evaluate a PCR assay based on amplification of the pneumolysin gene . Mice were treated with trovafloxacin to determine the decline in sensitivity of PCR as lung bacterial concentrations decreased and blood cultures became sterile . Forty-three mice were studied for up to 120 h after start of antibiotic treatment . PCR of buffy coat specimens was more sensitive than PCR of plasma . Only 21% of animals had a positive blood culture, whereas 77% of PCR buffy coat assays were positive . After 48 h of therapy all blood culture specimens were sterile, whereas buffy coat PCR was positive in 57.8% of specimens . PCR of buffy coat specimens was negative in all mice colonized nasally with Streptococcus pneumoniae and in rabbits with Escherichia coli bacteremia . Our results demonstrate that our PCR technique using buffy coat specimens is highly specific for invasive pneumococcal disease and remains positive in the majority of animals for at least 48 h after start of antibiotic therapy.

West Indian Med J, 2000 Dec, 49(4), 312 - 5
Evaluation of neonatal sepsis screening in a tropical area . Part I: Major risk factors for bacterial carriage at birth in Guadeloupe; Robillard PY et al.; This prospective study reports on screening for neonatal sepsis among 3,372 live births out of 6,060 consecutive deliveries at the University Hospital of Pointe-a-Pitre, Guadeloupe, during a 30-month period . Group B Streptococcus (GBS) was the most common pathogen, representing 46% (89/194) of positive blood cultures and 52% (335/637) of positive gastric aspirates . Although only 3,372 (55%) of all live births were screened, 637 (10%) had gastric bacterial carriage at birth; of those, 335 (5.5%) involved GBS . Similarly, there were 194 (3.2%) positive blood cultures, of which 89 (1.5%) involved GBS . In this report, all newborns who presented with a positive GBS blood culture had at least one of the external tests positive for GBS (gastric, ear canal, rectum and placenta) . Thirty-seven per cent (14/38) of positive neonatal blood cultures occurred in newborns with foetid liquor while in deliveries with intrapartum fever 16.5% (32/195) of blood cultures were positive . In our clinical practice, characteristics that were evident in the delivery room (without knowledge of prenatal follow-up) such as foetid liquor, intrapartum fever, prolonged rupture of membranes, foetal tachycardia and meconium staining were associated with the great majority of neonatal sepsis.

J Med Microbiol, 2001 Feb, 50(2), 173 - 6
Emergence of a high-level cefotaxime-resistant Streptococcus pneumoniae strain in New Zealand; Brett MS; An increase in the number of cefotaxime-resistant pneumococci referred for surveillance to a central laboratory in New Zealand occurred in 1997-1998 . The MIC of cefotaxime for 113 of 216 cefotaxime-resistant isolates of Streptococcus pneumoniae referred was > or = 4 mg/L . Most of the 113 isolates exhibited the same antibiotic resistance pattern and belonged to serotype 19F . To investigate the genetic relatedness of the isolates, 48 serotype 19F pneumococci with varying susceptibility to cefotaxime were further typed by macro-restriction analysis by use of pulsed-field gel electrophoresis . These results suggested that a multiresistant 19F strain of S . pneumoniae with high-level cefotaxime resistance had emerged from a pre-existing serotype 19F strain.

Laryngoscope, 2001 Feb, 111(2), 283 - 9
Free radical production by antibiotic-killed bacteria in the guinea pig middle ear; Takoudes TG et al.; OBJECTIVES: Oxygen free radicals are implicated in the pathogenesis of otitis media Recent investigations with animal models have demonstrated that free radical-mediated damage of the middle ear mucosa, measured as lipid hydroperoxide, occurs when the middle ear cavity is inoculated with Streptococcus pneumoniae . The present study was conducted to examine the effect of antibiotics on free radical-mediated damage in pneumococcal acute otitis media . STUDY DESIGN: Animal model of acute otitis media . METHODS: Seventy-eight guinea pigs underwent bilateral middle ear inoculation with 100 microl of 1) sterile saline as a control, 2) 50 microg/mL amoxicillin, 3) 10(7) colony forming units (CFU)/mL Streptococcus pneumoniae killed with 50 microg/mL amoxicillin, or 4) 10(7) CFU/mL S . pneumoniae . Animals were killed on postoperative day 1 or 5, and the middle ear mucosa was examined for lipid peroxidation as evidence of free radical damage . RESULTS: Mucosal lipid hydroperoxide was significantly elevated compared with control subjects on day 1 in both the antibiotic-killed S . pneumoniae group and the S . pneumoniae-infected group . On day 5, the S . pneumoniae-infected mucosa had significantly higher lipid hydroperoxide levels compared with the antibiotic-killed group and the control subjects . Histological studies confirmed mucosal edema and the presence of inflammatory cells in the infected groups . CONCLUSIONS: Antibiotic-killed bacteria seem to produce free radical-mediated damage to the middle ear mucosa in the early phase of acute otitis media . The clinical implication of this study is that free radical damage to the middle ear mucosa may occur in otitis media despite appropriate antibiotic therapy.

Cent Afr J Med, 2000 May, 46(5), 115 - 20
Prevalence, capsular type distribution, anthropometric and obstetric factors of group B Streptococcus (Streptococcus agalactiae) colonization in pregnancy; Moyo SR et al.; OBJECTIVE: To establish the prevalence, serotype distribution, anthropometry and obstetric factors of Group B Streptococcus (GBS) colonization in pregnant women . DESIGN: Cross sectional survey . SETTING: Chinhoyi General Hospital . SUBJECTS: 206 pregnant women attending the antenatal clinic at Chinhoyi General Hospital were systematically randomly sampled . MAIN OUTCOME MEASURES: All the isolates were serotyped on the basis of capsular polysaccharide (CHO) antigen designated, Ia, Ib, II, III, IV and V . RESULTS: 65 (31.6%) were carriers of GBS . The serotypes found were, type III (41.8%), type V (37.4%), type Ia (11.0%), type IV (3.3%), type Ib (3.3%) type II (1.0%) and 2.0% of the isolates were non-typable . All isolates were sensitive to penicillin and resistant to gentamycin . Colonization was more common in women with parity 0 to 2 (4.6%) and age group 20 to 24 years (43.1%) . There was some evidence (p = 0.063) to suggest that GBS was more often isolated from the vagina (12.6%) than from the rectum (6.3%) . CONCLUSION: There was a high prevalence of GBS colonization among pregnant women in Chinhoyi . Types III and V were the most common serotypes found.

Eur J Clin Microbiol Infect Dis, 2000 Dec, 19(12), 943 - 5
Streptococcus suis meningitis, a poacher's risk; Halaby T et al.; Streptococcus suis infection is a zoonosis that has been mainly reported in pig-rearing and pork-consuming countries . The most common disease manifestation is meningitis, often associated with cochleovestibular signs . The causative agent is Streptococcus suis serotype 2, found as a commensal in the tonsils of its natural host, the pig . Persons at risk are mostly those with an occupational exposure to domestic pigs or their meat products . A case of meningitis caused by Streptococcus suis in a poacher who had killed and butchered a wild boar is reported . It appears that wild boar hunters are at additional risk of contracting the disease.

Pathol Biol (Paris), 2000 Dec, 48(10), 901 - 5
{Nosocomial infections in mother and child: specific risks in the labour ward}; Simon L et al.; Nosocomial infection is a frequent and potentially lethal complication in obstetrics . The incidence of this complication may be underscored and an accurate surveillance system must be used in each obstetrics unit for infection control . This surveillance system should also identify the patients at risk for infection in order to improve prevention efforts . beta-lactam-sensitive streptococcus is often involved in obstetrical infections and a short antibio-prophylaxis is indicated in most obstetrical procedures . Disinfection strategy, guidelines for clinical practice and control charts should be established in each obstetrics unit to prevent nosocomial infections.

Bull Soc Pathol Exot, 2000 Nov, 93(4), 281 - 6
{Bacteriological and epidemiological data on Streptococcus pneumoniae in the hospital of southern Reunion Island}; Michault A et al.; We studied the epidemiology of Streptococcus pneumoniae in southern Reunion Island from 1993 to 1998 . Data were collected from the Centre hospitalier Sud Reunion . Incidence of pneumonia was calculated by applying published ratios to two different types of data (bacteriological, clinical) . Survey of pneumococci showed that antimicrobial resistance of S . pneumoniae to penicillin G appeared in 1994 and reached high levels in 1998 . We confirmed the increase of multiresistant strains among penicillin resistant S . pneumoniae . Serotyping the penicillin resistant S . pneumoniae has shown that these strains belonged to serogroups 9, 14, 19, 23 . The MIC determined in PRP showed that imipenem was the most active agent among beta-lactamin antibiotics followed by ceftriaxone . Strains with high resistance to amoxicillin are rare . Annual incidence of meningitis was almost 0.4 per 100,000 inhabitants . Estimation of pneumonia incidence was between 44 and 78 per 100,000 inhabitants . Incidence in Reunion Island is twice to three times lower than the incidence in France . Death rate from pneumoniae (10%) is similar to that in France . In the course of the study, the number of isolated S . pneumoniae increased . Changing socio-economic conditions are probably associated with the emergence of PRP since 1994 and the increase in numbers of infections . Pneumococcal infections in Reunion Island are becoming a public health problem of the same importance as in France.

J Leukoc Biol, 2001 Jan, 69(1), 50 - 6
Neutrophil survival is markedly reduced by incubation with influenza virus and Streptococcus pneumoniae: role of respiratory burst; Engelich G et al.; Bacterial superinfections are an important cause of morbidity and mortality during influenza A virus (IAV) epidemics . We demonstrate that incubation with the combination of IAV and Streptococcus pneumoniae caused marked reductions in survival of neutrophils in vitro compared with treatment with control buffer or IAV or S . pneumoniae alone . This cooperative effect was in part mediated by acceleration of neutrophil apoptosis as evidenced by increases in annexin-V binding and caspase-3 activation . However, GM-CSF did not increase survival of neutrophils exposed to IAV and S . pneumoniae . IAV enhanced neutrophil uptake of S . pneumoniae significantly . Furthermore, the combination of IAV and S . pneumoniae caused significantly more hydrogen peroxide production than IAV or S . pneumoniae alone . This increased respiratory burst activity contributed to the diminished neutrophil survival caused by IAV and S . pneumoniae . The NADPH oxidase inhibitor, diphenyleneiodonium, significantly improved survival of neutrophils treated with IAV and S . pneumoniae . These findings may help to explain the increased susceptibility of IAV-infected patients to infections with S . pneumoniae.

J Clin Laser Med Surg, 1999, 17(4), 171 - 7
In vitro study of the Nd:YAG laser effect on human dental enamel: optical and scanning electron microscope analysis; Pelino JE et al.; OBJECTIVE: The Nd:YAG laser irradiation of dental enamel was evaluated in enamel demineralization experiments in a Streptococcus mutans culture media . SUMMARY BACKGROUND DATA: Previous studies had shown that a continuous wave Nd:YAG laser at an energy of approximately 67 mJ may induce an increased acid resistance in human dental enamel when exposed to severe demineralization conditions . METHODS: Enamel windows of 3 x 4 cm in the buccal surface were irradiated with a continuous wave Nd:YAG laser at a wavelength of 1,064 microns using energy densities of from 83.75 to 187.50 J/cm2 . Enamel windows of 3 x 4 cm on the lingual surface served as control (without the laser irradiation) . The enamel windows were then exposed to a Streptococcus mutans culture media at a temperature of 37 degrees C for 15 and 21 days . The laser effects and demineralization were examined both by optical microscopy and scanning electron microscopy (SEM) . RESULTS: A comparison between the lased and the unlased windows of enamel showed fusion and recrystalization of the enamel and increased acid-resistance in all groups irradiated with the Nd:YAG laser . On the other hand, the 3 x 4 delimited enamel surfaces from the control group (not irradiated with the Nd:YAG laser) showed 100% demineralization . CONCLUSIONS: These findings are consistent with the finding that laser irradiation of dental results in significant reduction of the effective solubility of enamel mineral.

J Endod, 2000 May, 26(5), 268 - 70
Comparative evaluation of antibacterial effects of Nd:YAG laser irradiation in root canals and dentinal tubules; Berkiten M et al.; The antibacterial effects of the Nd:YAG laser on contaminated root canals and dentinal tubules were observed as the aim of this study . The samples were inoculated with Streptococcus sanguis (NCTC 7853) and Prevotella intermedia (NCTC 93336), and the effects of Nd:YAG laser were tested on these teeth . The specimens were lased with 1.8 W and 2.4 W Nd:YAG laser for 30 s, and the presence of bacteria in tubules was observed under light microscopy . The 1.8 W laser sterilized the tubules in 86.3% of sections inoculated with S . sanguis, whereas 2.4 W laser sterilized in 98.5% of the sections . Both laser powers sterilized all samples inoculated with P . intermedia . The scanning electron microscopic observations supported the light microscopic findings.

J Endod, 2000 Apr, 26(4), 236 - 9
In vitro study of the penetration of Streptococcus sanguis and Prevotella intermedia strains into human dentinal tubules; Berkiten M et al.; The persistent presence of bacteria in the root canal system often leads to the failure of treatment . The purpose of this study was to determine in vitro penetration of Streptococcus sanguis and Prevotella intermedia into dentinal tubules . Samples obtained from human teeth were inoculated with a strain of S . sanguis (NCTC 7853) and P . intermedia (NCTC 93336) for 20 days . Bacterial penetration into tubules was investigated at scanning electron microscopy and light microscopic level . The results showed that S . sanguis could penetrate into dentinal tubules 382.3 microns, whereas P . intermedia could penetrate 25.9 microns . It was observed that P . intermedia had not penetrated into all dentinal tubules . If penetration occurred the depth was quite limited.

J Endod, 2000 Apr, 26(4), 221 - 4
Antibiotic susceptibility of bacteria detected from the root canal exudate of persistent apical periodontitis; Noda M et al.; Intracanal exudates in persistent endodontic cases were sampled for detecting bacteria using a preculture method, and the antibiotic susceptibility of the bacteria identified was examined . Twelve species were recovered from 15 cases . The species most commonly detected were alpha-Streptococcus and Enterococcus . The results of the antibiotic susceptibility tests revealed that Enterococcus was highly resistant to antibiotics tested, especially to cephalosporin products . Enterococcus is known as one of the bacteria that show multidrug resistance . In cases of prolonged endodontic treatment, a specific antibiotic prescription would play an important role for efficient treatment . Collecting data about antibiotic susceptibility could be helpful . Identification, however, take approximately 2 wk and a further study to develop the method that rapidly informs us about the antibiotic susceptibility that might be needed.

Laryngorhinootologie, 2000 Dec, 79(12), 774 - 9
{Diagnosis and treatment of necrotizing fasciitis of the head and neck region}; Bloching M et al.; BACKGROUND: Necrotizing fasciitis of the head and neck is a rare occurrence . It spreads rapidly along fascial planes causing extensive necrosis; it often results in gangrene of the overlying skin . Mostly involved are immunodeficient patients with banal infections of the upper aerodigestive tract, small traumas, but also after surgical procedures . The "Federal Health Agency" of the Federal Republic of Germany estimates a number of 40 cases a year in Germany for all regions of the body . The mortality is about 20%-50% dependent on the localisation of this soft tissue infection . PATIENTS: Four cases of necrotizing fasciitis of the head and neck region, which were treated at the ENT-Department of the Martin Luther University Halle-Wittenberg since 1995, were described . RESULTS: Despite aggressive surgical debridement and intensive care medicine two patients died because of streptococcus-associated-toxic-shock-syndrome . In all patients we found a diabetes mellitus as a known risk factor for this necrotizing soft tissue disease . In two of four patients with cervical involvement mediastinitis was diagnosed as a complication . The CT-scan showed this mediastinal spread only in one case . CONCLUSIONS: Only rapid diagnosis and surgical treatment with radical debridement can influence the disease positively . Thoracal CT-scan is necessary in all cases of cervical necrotizing fasciitis because of the high risk of mediastinal involvement . A strong complication is a streptococcus-associated-toxic-shock-syndrome, which should be prevented because it is often associated with a lethal outcome . Penicillin G and clindamycin are advocated for antibiotic treatment.

Ned Tijdschr Geneeskd, 2001 Jan 6, 145(1), 33 - 6
{Loss of an eye due to hyper-IgE syndrome after corneal transplantation}; Strijdhorst B et al.; A 37-year-old patient with bilateral keratoconus underwent a perforating cornea transplantation after acute onset of pain and hydrops of the right cornea . One day after operation endophthalmitis developed, caused by a viridans streptococcus . Hyper-IgE syndrome was suspected because of the patient's crude facial features . His medical history brought up additional symptoms of this disease . IgE levels were extremely elevated (7320 kU/l), the eosinophil count was slightly raised (0.25 x 10(9)/l) . The patient was treated with several local antibiotics but his vision was only light perception at the time of discharge from the hospital . This case illustrates how an usually successful operation may have a disastrous outcome in case of late diagnosis of the hyper-IgE syndrome . The hyper-IgE syndrome can be recognized by the characteristic facial features in combination with the often extensive (juvenile) medical history with infections, and by elevated serum IgE levels . As patients with the hyper-IgE syndrome are extremely susceptible to develop infections, prophylactic antibiotic therapy is indicated in surgical procedures.

Int J Clin Pract, 2000 Oct, 54(8), 497 - 503
Moxifloxacin versus cephalexin in the treatment of uncomplicated skin infections; Parish LC et al.; The efficacy and safety of oral moxifloxacin (400 mg once daily, 7 days) versus cephalexin (500 mg three times daily, 7 days) were compared in a prospective, multicentre, randomised, double-blind trial in 401 adults with uncomplicated skin infections . Clinical outcome was evaluated in 351 patients . Moxifloxacin proved to be as effective as cephalexin both clinically (90% versus 91%, respectively) and bacteriologically in eradicating the most frequently isolated pathogen Staphylococcus aureus (92% and 93%, respectively) . Moxifloxacin was more effective than cephalexin in eliminating Streptococcus spp . (90% and 82%, respectively) . Drug-related adverse events were comparable in both treatment groups with the most frequently reported being nausea in the moxifloxacin-treated patients and headache in the cephalexin-treated patients . Medication was discontinued due to unwanted reactions in 3% of the moxifloxacin- and 4% of the cephalexin-treated patients . Moxifloxacin, 400 mg once daily for 7 days, is as safe and effective as cephalexin 500 mg three times daily for 7 days in the treatment of uncomplicated skin infections.

Med Klin (Munich), 2000 Dec 15, 95(12), 678 - 82
{Prevention of infection with Streptococcus pneumoniae}; Randerath O et al.; Streptococcus pneumoniae is the most common etiologic agent in outpatients pneumonia . Pneumococcal infections are often associated with high mortality risk in immunocompromised patients . An increasing resistance of Streptococcus pneumoniae to antibiotics is observed worldwide . This led to the official recommendation by the STIKO to use the vaccination in special risk groups . The commercially available 23-valent polysaccharide vaccine produces a reliable immune response against pneumococcal infection in children aged over 2 years and adults . The recommendation should be more realized in practice.

Shock, 2001 Jan, 15(1), 29 - 34
TNF mediates a murine model of Addison's crisis; Koniaris LG et al.; Addison's crisis is the most serious complication of adrenal insufficiency . To elucidate the mechanism of this disorder following infection, the role of TNF in adrenalectomized murine models of Addison's crisis and Addison's disease (chronic hypoglucocorticoidism) were examined . Adrenalectomy conferred a 40-fold increased sensitivity to the lethal effects of lipopolysacharride (LPS) (P < .001) . Enhanced sensitivity to LPS was found to increase with duration of adrenal insufficiency (P < .02) . Enhanced lethality to heat-killed Streptococcus pneumonia was also demonstrated (P < 0.02) . Necropsy of endotoxin-killed adrenalectomized mice demonstrated similar pathologic findings to those found by others when the control mice were administered a lethal dose of either LPS or TNF . Adrenalectomized TNF receptor Ia and Ib double null mice were demonstrated to be resistant to the lethal effects of LPS (P < 0.02) . Pretreatment with anti-TNF, but not control antisera, was found to prevent death in LPS-treated wild-type adrenalectomized mice as well (P < 0.02) . Studies into the mechanism by which TNF was precipitating Addison's crisis demonstrated enhanced sensitivity to TNF (3-fold; P < 0.02), and a marked increase in serum TNF concentration (approximately 5-fold; P < 0.001) following LPS challenge . The effect of TNF upon long-term survival in adrenalectomized mice was examined in TNF-receptor Ia- and Ib-deficient mice . Deficiencies in either the TNF-receptor Ia or Ib was noted to confer a survival advantage relative to colony controls following adrenalectomy (P < 0.02) . In summary, both LPS-induced Addison's crisis and chronic adrenal insufficiency are disorders of TNF disregulation . Based upon these data, therapeutic strategies targeted at controlling TNF in adrenal insufficiency are suggested.

Enferm Infecc Microbiol Clin, 2000 Dec, 18(10), 506 - 11
{Presence of conjugative transposon Tn1545 in strains of Streptococcus pneumoniae with mef(A), erm(B), tet(M), catpC194 and aph3'-III genes}; Seral C et al.; We studied the association of MLS resistance genes (erm(B) and mef(A) with others non-MLS resistance genes: tet(M) (tetracycline and minocycline), catpC194 (chloramphenicol) and aph3'-III (kanamycin) in order to know how is selected the multiresistant in Streptococcus pneumoniae . The tet(M) and catpC194 genes were present very often in the pneumococci with the erm(B) gene but the aph3'-III was found only in four strains . Tn1545 was nearly always the responsible for the dissemination of these genes . In contrast, mef(A) was not associated with tet(M) and and catpC194 and is disseminated in a different conjugative transposon . The linkage of multiple antibiotic resistance genes on the same mobile element is of importance for public health, because the use of one antibiotic selects for the transposon which carries multidrug resistance genes.

Acta Odontol Scand, 2000 Dec, 58(6), 285 - 92
Efficacy of a slow-release device containing fluoride, xylitol and sorbitol in preventing infant caries; Aaltonen AS et al.; A novel slow-release administration device, the "Fall-Asleep Pacifier" (FAP), was studied as a prophylactic measure against mutans streptococcal oral infection and dental caries in a risk group of 1-year-old children by comparing the test (T, n = 34) and control (C, n = 88) groups in a prospective cohort study . In the T group the children received their fluoride tablets (Fludent, containing NaF corresp . 0.25 mg F0- , xylitol 159 mg and sorbitol 153 mg) in the evenings in FAP . In the C group the children received the same dose of Fludent crushed in food in the evenings . The proportion of children, whose plaque samples from the upper incisors were mutans streptococcus positive at the age of 24 months, was significantly (P < 0.05) greater in group C (25%) than in group T (9%) . The children in the T group developed significantly (P < 0.001) less (none) new dentinal carious lesions in their primary dentitions than the children in the C group between 2 and 3 1/2 years of age . Fifty-four percent of the children to whom the FAP was offered complied with regular use of it . The beneficial effect observed in the T group compared with the C group was apparently mostly due to the administration mode via FAP, which could prolong the intra-oral bioavailability of the prophylactic preparation.

S Afr Med J, 2000 Nov, 90(11), 1116 - 21
Prevalence of nasopharyngeal antibiotic-resistant pneumococcal carriage in children attending private paediatric practices in Johannesburg; Huebner RE et al.; OBJECTIVES: To determine the nasopharyngeal carriage rate, serogroups/types, and antibiotic resistance of Streptococcus pneumoniae in children attending paediatric practices in the private sector in Johannesburg and to relate patterns of resistance to antimicrobial exposure and other demographic characteristics in individual children . DESIGN: A total of 303 children aged from 1 month to 5 years were recruited from eight private paediatric practices in northern Johannesburg . Nasopharyngeal samples were taken and parent interviews were conducted . RESULTS: Pneumococci were isolated from 121 children (40%) . The most common serotypes were 6B, 19F, 6A, 23F, 14, and 19A . Carriage was significantly associated with prior hospital admission (odds ratio 1.89) and day care attendance (odds ratio 2.31) and was negatively associated with antibiotic use within the previous 30 days . Antibiotic resistance was found in 84 isolates (69.4%); 45 (37.2%) were multiply resistant . One-third of the pneumococci showed intermediate level resistance to penicillin and 12.4% were highly resistant . There was a high level erythromycin resistance in 38% of the isolates . A total of 94/214 children (42%) had recently used antibiotics and were four times more likely to carry antibiotic-resistant pneumococci (P < 0.05) . CONCLUSION: Pneumococcal resistance was significant in this group of children with easy access to paediatric services and antibiotic use . The implication of such high resistance for the treatment of pneumococcal diseases is that high-dose amoxicillin is the preferred empirical oral therapy for treatment of otitis media . Ceftriaxone or cefotaxime should be used in combination with vancomycin for the treatment of meningitis until a cephalosporin-resistant pneumococcal cause is excluded . Intravenous penicillin or ampicillin will successfully treat pneumococcal pneumonia in this population . Antimicrobial resistance among pneumococci colonising children in the private sector has increased dramatically in recent years.

Acta Paediatr Suppl, 2000 Dec, 89(435), 44 - 50
Streptococcus pneumoniae in children in Spain: 1990-1999; Fenoll A et al.; This study analyses the serogroups/types (SGTs) and resistance to penicillin and erythromycin of 3921 strains isolated from 1990 to 1999 in children aged 0-14 y in Spanish hospitals of all the autonomous communities . Based on the age of the children, strains have been divided into five groups: 0-6 mo, > 6-1 y, > 1-2 y, > 2-5 y and > 5 y . While only eight SGTs were responsible for 80% of the infections in children from 6 mo to 2 y of age, this number increased to 11 and 16 for the groups > 2-5 y and > 5-14 y, respectively . SGTs 6, 14 and 19 were prevalent in blood and otic exudates . SGTs 1, 4, 5, 12 and 18 were more frequent in invasive disease but serotype 3 was clearly associated with otitis . Serotypes I and 5 were quite significant in children of over 2 y of age, and this should be taken into account in future vaccine formulations . CONCLUSION: Although high, the rate of penicillin resistance in the paediatric population has remained stable in recent years . Conversely, erythromycin resistance is still increasing in our country . Coverage by the 7-valent vaccine was 78 and 81% for blood and otic isolates, respectively . These coverage levels would be increased by 9% and 3% if 9-valent (plus 1 + 5 serotypes) were used and by an additional 2.6% and 7.6% using the 11-valent (plus 3 + 7) formulation.

Acta Paediatr Suppl, 2000 Dec, 89(435), 40 - 3
Epidemiology of Streptococcus pneumoniae in Italian children; Principi N et al.; In Italy, data regarding the aetiological role, antibiotic resistance, and serotype distribution of isolates of Streptococcus pneumoniae are scarce and based on very small population samples . We found that S . pneumoniae caused about 30% of lower respiratory tract infections and 15% of acute otitis media infections in Italian children . The incidence of S . pneumoniae meningitis in subjects aged 0-4y was 1.1 x 100,000 . In children <5 y of age with meningitis, the most common S . pneumoniae serotypes were, in rank order, 14, 6, 23, 1 and 4; among 53 nasopharyngeal carriers the most frequent serotypes were 6 and 19 . The actual percentage of resistance of S . pneumoniae to penicillin is 10.2%, while for macrolides it reaches 25.5% . More data on the distribution of serotypes in Italian children are urgently needed in order to obtain a better understanding of the impact of the new pneumococcal vaccines.

Acta Paediatr Suppl, 2000 Dec, 89(435), 3 - 10
Epidemiology of invasive pneumococcal infections in children aged 0-6 years in Denmark: a 19-year nationwide surveillance study; Kaltoft et al.; The impact of the new pneumococcal conjugate vaccines on invasive disease burden in Danish children was evaluated by analysing the results from the last 19 years of a nationwide surveillance of invasive pneumococcal infections . During 1981-1999, the Streptococcus Unit at Statens Serum Institut, Copenhagen, received 1123 invasive pneumococcal isolates from children aged 0-6 years . Nearly 72% (71.8%) of the pneumococcal isolates were from children aged <2 y . The median ages of children with pneumococcal meningitis and bacteraemia were 10.2 mo and 15.9 mo, respectively . The incidence of pneumococcal meningitis remained stable during the study period . The mean annual incidence rates of pneumococcal meningitis among children aged <1, <2, and <7 years were 17.4, 12.4, and 4.3 per 100,000, respectively, during 1981-1999 (overlapping age groups are used throughout this article to facilitate the comparison of incidence data from different countries or among different studies) . The annual incidence of pneumococcal bacteraemia increased from 1981 to 1996, after which a slight fall was noted . During the last six years of the study period, the mean annual incidence rates of bacteraemia were 30.1, 32.5, and 14.0 per 100,000 children aged < 1, < 2, and < 7 years . In the 1990s, pneumococcal isolates with reduced sensitivity to penicillin (0-5% each year) and erythromycin (7.4% in 1999) emerged as a cause of invasive infections in children aged 0-6 years in Denmark . During 1981-1999, 10 serotypes (1, 4, 6A, 6B, 7F, 9V, 14, 18C, 19F, 23F) caused 82% of invasive infections in Danish children . Importantly, no significant temporal changes in overall serotype distribution or differences in serotype distributions between girls and boys could be documented during the study period . CONCLUSION: According to the Kaiser Permanente trial, the 7-, 9-, and 11-valent pneumococcal conjugate vaccines will probably cover around 60%, 70%, and 80%, respectively, of all invasive pneumococcal infections in Danish children aged 0-6y, corresponding to 12-14 episodes of meningitis and 40-60 episodes of bacteraemia per year.

Acta Paediatr Suppl, 2000 Dec, 89(435), 27 - 9
Epidemiology of pneumococcal infections in French children; Gaudelus J et al.; Since 1977, resistance to beta-lactams and other families of antibiotics among isolates of Streptococcus pneumoniae has increased alarmingly worldwide . France is particularly affected by this phenomenon; in 1997 the French National Reference Centre for Pneumococci reported that 44% of S . pneumoniae strains were penicillin non-susceptible (PNSS) . Furthermore, resistance to macrolides (53%) and sulphonamides (37%) was comparable; in addition, >50% of PNSS had a high level of resistance to penicillin and were multiresistant . The highest frequency of resistance is observed in children, particularly those with acute otitis media (AOM) . CONCLUSION: The clinical consequences of increasing antibiotic resistance are evident for meningitis and AOM, prompting clinicians to consider alternative agents such as high-dose cefotaxime (300 mg/ kg/d) or ceftriaxone (100mg/kg/d) plus vancomycin (60 mg/kg/d) for meningitis, and high-dose amoxicillin (> 80 mg/kg/d) or ceftriaxone (50 mg/kg/d) for AOM.

Acta Paediatr Suppl, 2000 Dec, 89(435), 22 - 6
Epidemiology of meningitis and bacteraemia due to Streptococcus pneumoniae in The Netherlands; Spanjaard L et al.; In The Netherlands, accurate data on the epidemiology of pneumococcal meningitis are available through a clinical microbiology laboratory-based national surveillance of cerebrospinal fluid isolates . The Netherlands Reference Laboratory for Bacterial Meningitis receives isolates of about 80% of all meningitis cases and about 40% of bacteraemic cases . The incidence of pneumococcal meningitis has increased slowly from 1.0/100,000 in 1990 to 1.5/100,000 since 1996 . The highest age-specific incidence of meningitis was observed in children < 5 y of age (8.2/100,000 in 1999) . Of all isolates, 35% were from children < 5 y of age . The number of isolates from non-meningitis patients with bacteraemia increased considerably since the early 1990s, especially among the elderly . The highest incidence was found in 1996, probably owing to a relatively severe winter . During 1995-1999, pneumococcal meningitis in The Netherlands was caused mainly by serotypes 3, 6B, 7F, 9V, 14, 18C, 19F, and 23F . Of the cases in children < 15 y, almost half were caused by serotypes 6B, 14, 18C, and 19F . The serotypes present in the 23-valent polysaccharide and 7-valent conjugate vaccines accounted for 87% and 47% of all meningitis cases, respectively . Pneumococcal resistance to penicillin in The Netherlands is still low, at about 1% . Genotypically, resistant strains belong to many clones . Horizontal transfer of capsular genes occurs among these isolates . In The Netherlands, 45% of cases of pneumococcal meningitis have severe predisposing factors . The case-fatality rate was significantly higher among patients with impaired immunity than among those with a break in the integrity of the dura.

Aust Vet J, 2000 Nov, 78(11), 763 - 8
A clinical trial to evaluate the effectiveness of antibiotic treatment of lactating cows with high somatic cell counts in their milk; Shephard RW et al.; OBJECTIVE: To determine the effectiveness of treatment of lactating cows with high somatic cell counts in milk . DESIGN: Randomised clinical trial . METHODS: Single pooled quarter samples of milk were obtained from cows with somatic cell counts above 500,000 cells/mL on fifty farms . Milk samples were cultured for known mastitis bacterial pathogens . Cows were randomly allocated to treated and untreated groups . Treated cows received both intramammary cloxacillin and parenteral erythromycin . Single pooled quarter milk samples were obtained at 6 weeks after treatment and were cultured for the presence of pathogenic bacteria . The percentage of samples with no growth at the post-treatment culture was used as an estimate of the bacteriological cures for each pathogen type and for each treatment group . Somatic cell counts of cows were compared between treatment groups and within pathogen group . The number of cows that completed a full lactation were compared between each treatment group and within each pathogen group . RESULTS: Treatment had no effect upon bacteriological cures, irrespective of pathogen present or the presence of bacteria during the previous lactation . There was no effect of treatment upon somatic cell count except for cows infected with Streptococcus dysgalactiae in which treatment caused a significant lowering of cell counts . This effect was not present in the subsequent lactation . Treatment of chronically infected cows did not alter the probability of a cow completing a full lactation but did improve the probability of newly infected cows being retained for the next lactation . Twenty-eight of 214 treated cows developed clinical mastitis in more than one quarter after treatment, thus indicating a poor technique by farmers for the insertion of intramammary antibiotics . CONCLUSIONS: Treatment during lactation of cows with high somatic cell counts in milk is ineffective in reducing bacterial infections and in reducing somatic cell counts to acceptable numbers.

Nihon Kokyuki Gakkai Zasshi, 2000 Nov, 38(11), 836 - 8
{Safety of and untoward reactions to 23-valent pneumococcal vaccine: a prospective study}; Suda T; The study objective was to demonstrate the safety of Streptococcus pneumoniae vaccine in 430 geriatric patients at high risk of infection . The reactions after inoculation were classified as follows: (1) Grade 1: slight pain at the site of injection; mild systemic fatigue to improve within 3 days . (2) Grade 2: symptoms of swelling, erythema, or pain lasting for more than 3 days; inability to move upper limb due to pain; systemic symptoms such as a temperature above 38 degrees centigrade . (3) Grade 3: reactions requiring immediate medical therapy . Seventy patients (16.3%) showed inoculation reactions, and 360 (83.7%) were asymptomatic . Of the symptomatic reactions, 50 (11.6%) were grade 1.17 (4.0%) grade 2, and 3 (0.7%) grade 3 . About 5% of the patients with grade 1 and 2 reactions needed special management . One chronic heart failure patient complained of severe heart failure symptoms after inoculation.

J Trop Pediatr, 2000 Dec, 46(6), 371 - 4
Acute respiratory tract infections in Indian children with special reference to Mycoplasma pneumoniae; Pandey A et al.; A total of 70 Indian children of either sex and under 5 years of age who were admitted to the All India Institute of Medical Sciences, New Delhi during a 1-year period (January 1994-December 1994) with complaints suggestive of acute respiratory tract infections (ARTI), were investigated for bacterial aetiology of infection with special reference to Mycoplasma pneumoniae . Microbial aetiology could be established in 44/70 (62.8 per cent) of cases of ARTI . Mycoplasma pneumoniae infection was seen in 21/70 (30 per cent), aerobic bacteria in 14/70 (20 per cent), Chlamydia pneumoniae in 2/70 (2.8 per cent), and mixed infection with mycoplasma either with bacteria and/or chlamydia in 7/70 (10 per cent) . However, in 26/70 (37.1 per cent) cases no cause could be detected . Diagnosis of infection with M.pneumoniae was based on culture in 2/20 (10 per cent) cases, antigen detection in throat swab by indirect immunofluorescence assay using specific antibody in 16/70 (22.8 per cent) cases, and demonstration of IgM antibody in serum by serodia Myco II particle agglutination test in 17/70 (24.2 per cent) . Streptococcus pneumoniae (9/70, 12.8 per cent) and Staphylococcus aureus (5/70, 7.1 per cent) were the aerobic isolates from blood in these patients . Results of this study indicate that M.pneumoniae plays a significant role in respiratory tract infection in an Indian paediatric population . Rapid diagnostic procedures, such as antigen detection and IgM antibody demonstration, should be used more widely to determine the infective aetiology early in the course of illness . The study also highlights the mixed aetiology in ARTI in children, which has important therapeutic implications.

J Trop Pediatr, 2000 Dec, 46(6), 365 - 7
Persistent rhinorrhoea in rural Indian children: prevalence and consequences; Cherian T et al.; To determine whether persistent rhinorrhoea constitutes a significant problem requiring intervention, 17 rural day care centres (Balwadis) in Tamilnadu, India, were visited . Among 414 children in the Balwadis 92 (22 per cent) children with persistent rhinorrhoea (15 days duration or longer) were identified . Demographic and clinical data and nasopharyngeal swabs for bacterial culture were obtained from 56 such children and 91 age-matched controls from the same Balwadi . Type of housing or nutritional status did not appear to be significant risk factors . There was a significantly higher number of children aged 5-15 years in the household of cases as compared to controls (1.23 +/- 1.08 vs . 0.83 +/- 0.95, p = 0.02) . Other illnesses were noted in 25 (44.6 per cent) cases and seven (7.7 per cent) controls (OR 11.5; CI, 4.13-33.4; p < 0.00001) . Notably, chronic ear discharge was noted in 6 (11.7 per cent) cases but in none of the controls (p = 0.007) . Streptococcus pneumoniae was isolated from nasopharyngeal swabs in 42/49 (85.7 per cent) cases and 44/80 (55 per cent) controls (p < 0.001) and H . influenzae from seven cases and five controls; S . pneumoniae was isolated in all children with chronic ear discharge and H . influenzae from one child . Serotypes of pneumococci commonly associated with otitis media, i.e., types 6, 14, 19, and 23 were isolated from 25 (51 per cent) cases and 16 (20 per cent) controls (OR 4.17; 95% CI, 1.78-9.85; p < 0.001) . Persistent rhinorrhoea, presumably due to pneumococcus, is a common condition among rural Indian children and appears to be associated with chronic otitis media.

Commun Dis Intell, 2000 Nov, 24(11), 340 - 3
Antimicrobial resistance in Streptococcus pneumoniae: a decade of results from south-western Sydney; Gosbell IB et al.; We report the emerging drug-resistance in Streptococcus pneumoniae seen by the South Western Area Pathology Service (SWAPS) from 1 January 1990 to 31 July 2000 . SWAPS performs all the pathology testing for the public hospitals in the South Western Sydney Area Health Service, which serves a population of 700,000; 120,000 separations occur at these hospitals annually . In all, 2,265 patients submitted specimens yielding S . pneumoniae . These included respiratory tract specimens, blood cultures, eye swabs and cerebrospinal fluid (CSF) . Resistance to penicillin, cefotaxime, and non-beta-lactam antibiotics, especially cotrimoxazole, has emerged over the 1990s . From 1997 onwards, around 10 per cent of CSF and blood culture isolates demonstrated penicillin-resistance and 5 per cent showed cefotaxime-resistance . In 2000, 35 per cent of pneumococci from sites other than CSF and blood exhibited resistance to penicillin and 15 per cent showed resistance to cefotaxime . Resistance to other agents also increased over the decade . In 2000, 76 per cent of all isolates were resistant to cotrimoxazole, 26 per cent to erythromycin and 24 per cent to tetracyclines . Rifampicin-resistance was negligible over the decade, and vancomycin-resistance was absent . Antibiotics currently used for empirical treatment of certain S . pneumoniae infections may now need to be reviewed.

Am J Public Health, 2001 Jan, 91(1), 142 - 5
Sentinel surveillance as an alternative approach for monitoring antibiotic-resistant invasive pneumococcal disease in Washington State; Jernigan DB et al.; OBJECTIVES: As an alternative to statewide, mandated surveillance for antibiotic-resistant Streptococcus pneumoniae, a sentinel surveillance network of 27 hospitals was developed in Washington State . METHODS: The utility of targeted surveillance in population centers was assessed, current laboratory susceptibility testing practices were evaluated, and a baseline of pneumococcal resistance in Washington State was obtained for use in a statewide campaign promoting the judicious use of antibiotics . RESULTS: Between July 1997 and June 1998, 300 cases were reported; 67 (22%) had diminished susceptibility to penicillin . Only 191 (64%) were fully tested with penicillin and an extended-spectrum cephalosporin (ESC) as nationally recommended; 10.5% were resistant to penicillin and 6.8% were resistant to an ESC . The number of isolates inadequately tested declined through the year . The findings were similar to those from more comprehensive active surveillance in Oregon for the same time period . CONCLUSIONS: Targeted surveillance may be an adequate alternative for limited monitoring of antibiotic resistance for states that choose not to mandate reporting.

Zhonghua Kou Qiang Yi Xue Za Zhi, 1997 Nov, 32(6), 356 - 9
{Antibacterial activity of histidine-rich polypeptides in human parotid saliva}; Wu Q et al.; Two ultrasensitive antibacterial assays were applied to determine the antibacterial activity of histidine-rich polypeptides (HRPs) in human parotid saliva . The results not only confirmed the potent antibacterial activity of HRPs against Streptococcus mutans MT6R, but also showed for the first time that HRPs were effectively antibacterial to Staphylococcus aureus ATCC 25923, Escherichia coli ML-35p and Pseudomonas aeruginosa ATCC 27853 . Among HRPs, HRP3, HRP5 and HRP6 were the major antibacterial components which were active against S . mutans, S . aureus, E . coli and P . aeruginosa, whereas HRP1 was only effective against E . coli . S . sanguis was resistant to the action of HRPs . These results suggest that HRPs are actually a family of endogenous antibiotic peptides with broad antimicrobial spectrum including fungi, Gram-positive and Gram-negative bacteria and may play an important role in the prevention of various infection diseases in the oral cavity as well as in the resistance to caries.

Zhonghua Kou Qiang Yi Xue Za Zhi, 1997 Sep, 32(5), 269 - 71
{The effect of chlorhexidine varnish system on Streptococcus mutans in fissure plaques}; Fan M et al.; A chlorhexidine varnish system and a controlled releasing varnish were prepared by the authors . The release rate of chlorhexidine in vitro and the effects on S . mutans and S . sanguis in vivo were determined . The results showed that the system could selectively inhibit the growth of S . mutans in fissure plaque and had no effect on S . sanguis . The period of interaction between the layer of varnish and plaque was prolonged by the control-releasing reagent . The study suggests that the chlorhexidine varnish system is effective of anticaries and can maintain microflora balance in oral bacteria.

Lin Chuang Er Bi Yan Hou Ke Za Zhi, 1998 Jul, 12(7), 334 - 6
{Microbiology of acute pharyngitis and acute tonsillitis and treatment with Taileqi troches}; Xiao H et al.; A qualitative analysis of microflora from pharynx of 100 cases of acute pharyngitis and acute tonsillitis was performed . These patients were randomly divided into two groups so as to assess treatment effect of Taileqi troches vs Amoxycillin . Results showed that beta-hemolytic streptococcus, Klebsiella pneumoniae, staphylococcus aureus were the most common organisms causing diseases . The predominant anaerobic organisms were bacteroides melaninogenicus, eptostrep . These findings suggest that anaerobic bacteria may play a pathogenic role in infection of the pharynx . The effective rate of treatment with troche alone were 86 percent, roughly consistent with Amoxycillin group . No adverse effect was observed.

Nippon Rinsho, 2000 Dec, 58(12), 2551 - 60
{Penicillin-resistant Streptococcus pneumoniae infections: current trends in epidemiology and antibiotic chemotherapy}; Tateda K et al.; The world-wide emergence of penicillin-resistant Streptococcus pneumoniae has led to dilemmas in the management of pneumococcal infections . Furthermore, most penicillin-resistant pneumococci are simultaneously resistant to a wide variety of other antibiotics, including cephalosporins, macrolides and tetracyclines . Epidemiological surveys in Japan demonstrated that 30-50% of clinical isolates were penicillin-insusceptible(MIC: > or = 0.125 microgram/ml) . At present time most penicillin-resistant pneumococcal pneumonia cases are well treated with penicillin or cephalosporin, but significant numbers of treatment failures were reported in meningitis patients . Data from healthy mice model of pneumonia clearly showed that carbapenems and vancomycin are more active than cefotaxime or penicillin in high dose . Careful and continuous surveys for trends in antibiotic resistance and clinical impacts of antibiotic-resistant pneumococci are warranted.

Am J Manag Care, 2000 Dec, 6(23 Suppl), S1197 - 201
Is drug resistance affecting treatment outcomes?
Bishai W.
Antimicrobial drug resistance is a growing concern for the medical community . Although cases of drug resistance to Streptococcus pneumoniae are on the increase, there has been no change in mortality rates . The fact that the medical literature shows no proven correlation between drug-resistant S pneumoniae and clinical failure suggests that concerns about drug resistance in S pneumoniae may be overstated . Therefore, in treating community-acquired pneumonia, physicians should also weigh other important considerations such as pharmacology, safety, tolerability, and dosing convenience.

Am J Manag Care, 2000 Dec, 6(23 Suppl), S1189 - 96
Resistance among Streptococcus pneumoniae: patterns, mechanisms, interpreting the breakpoints; Brueggemann AB et al.; Streptococcus pneumoniae is a frequent cause of respiratory tract infections . In the United States and worldwide, antimicrobial resistance of S pneumoniae has complicated the management of infections caused by this organism . In the United States, antimicrobial resistance with S pneumoniae has evolved almost entirely during the 1990s . Resistance currently exists at high rates with beta-lactams, macrolides, tetracyclines, chloramphenicol, and trimethoprim/sulfamethoxazole . Multiresistant strains--strains that are resistant to penicillin plus at least 2 other antimicrobial classes--are also increasing in prevalence . Fluoro-quinolone resistance remains at low levels in the United States . Control of the problem of antimicrobial resistance will require more judicious and appropriate use of antimicrobials, the development of new agents with novel targets of action, and strategies for preventing disease from occurring in the first place . In addition, the pursuit of an understanding of resistance mechanisms and pharmacodynamics as they relate to clinical outcome must be an ongoing effort, and that knowledge must be applied to the development of more effective approaches for the treatment of infections caused by S pneumoniae.

J Med Dent Sci, 1998 Jun, 45(2), 135 - 9
In vitro testing of a denture cleaning method using ozone; Oizumi M et al.; The purpose of this study was to compare the microbicidal effect of gaseous ozone with that of ozonated water in order to determine its usefulness as a method for disinfecting dentures . Although a large number of research studies have been done on the bactericidal effect of ozone, little is known about its microbicidal effects on oral microorganisms . Therefore, we tested the effect of ozone on three standard strains of oral microorganisms: Streptococcus mutans (strain IID 973), Staphylococcus aureus (strain 209-P), and Candida albicans (strain LAM 14322) . When the gaseous ozone injection method was used, the numbers of cells of all three strains decreased to 1/10(5) at 1 min, and by 3 min they were below the detection limit . Thus, the microbicidal effect of gaseous ozone was ascertained in a short time . In contrast, when ozonated water at 1 ppm and 3 ppm was used, C . albicans decreased to 1/10 . A 700 mg/h ozone production level was needed to prepare 1 ppm ozonated water, whereas 20 mg/h of ozone was required by the gaseous ozone generator . These findings indicate that direct exposure to gaseous ozone seems to be a more effective microbicide compared with ozonated water, and that gaseous ozone can be clinically useful for disinfection of dentures.

Environ Microbiol, 1999 Feb, 1(1), 53 - 64
Evidence for recent intergeneric transfer of a new tetracycline resistance gene, tet(W), isolated from Butyrivibrio fibrisolvens, and the occurence of tet (O) in ruminal bacterial; Barbosa TM et al.; We have previously reported high-frequency transfer of tetracycline resistance between strains of the rumen anaerobic bacterium Butyrivibrio fibrisolvens . Donor strains were postulated to carry two TcR genes, one of which is transferred on a novel chromosomal element . It is shown here that coding sequences within the non-transmissible gene in B . fibrisolvens 1.230 are identical to those of the Streptococcus pneumoniae tet(O) gene . This provides the first evidence for genetic exchange between facultatively anaerobic bacteria and rumen obligate anaerobes . In contrast, the product of the transmissible TcR gene shares only 68% amino acid sequence identity with the TetO and TetM proteins and represents a new class of ribosome protection tetracycline resistance determinant, designated Tet W . The tet(W) coding region shows a higher DNA G + C content (53%) than other B . fibrisolvens genes or other ribosome protection-type tet genes, suggesting recent acquisition from a high G + C content genome . Tet(W) genes with almost identical sequences are also shown to be present in TcR strains of B . fibrisolvens from Australian sheep and in TcR strains of two other genera of rumen obligate anaerobes, Selenomonas ruminantium and Mitsuokella multiacidus . This provides compelling evidence for recent intergeneric transfer of resistance genes between ruminal bacteria . Tet(W) is not restricted to ruminal bacteria, as it was also present in a porcine strain of M . multiacidus.

Cell Microbiol, 2000 Apr, 2(2), 145 - 54
Two distinct pathways for the invasion of Streptococcus pyogenes in non-phagocytic cells; Molinari G et al.; Adherence to and invasion of epithelial cells represent important pathogenic mechanisms of Streptococcus pyogenes . A fibronectin-binding surface protein of S . pyogenes, Sfbl protein, has been implicated in both adherence and invasion processes . Invasion of Sfbl-containing strains has been suspected to be responsible for the failure of antibiotics treatment to eradicate S . pyogenes . In this study, we tested the adherence and invasion properties of two well-characterized clinical isolates: A40, which expresses Sfbl; and A8, which is Sfbl negative and is unable to bind fibronectin . In strain A40, Sfbl was the main factor required for attachment and invasion by using fibronectin as a bridging molecule and the alpha5beta1 integrin as cellular receptor . The uptake process was characterized by the generation of large membrane invaginations at the bacteria-cell interface without evidence of actin recruitment or cellular injury . A40 cells were located in phagosomes and, only 24 h after infection, a consistent part of the bacterial population reached the cytoplasm . In contrast, uptake of strain A8 required major rearrangements of cytoskeletal proteins underneath attached bacteria . In A8, a proteinaceous moiety was involved, which does not interact with alpha5beta1 or need any known bridging molecule . Bacterial attachment stimulated elongation and massive recruitment of neighbouring microvilli, which fused to surround streptococcal chains . They led to the generation of large pseudopod-like structures, which engulfed bacteria that were rapidly released and replicated in the cytoplasm . The identification of two completely different uptake pathways reported here provided further evidence regarding the diversity of S . pyogenes isolates and might contribute towards understanding the pathogenesis and persistence of S . pyogenes.

Cell Microbiol, 1999 Sep, 1(2), 157 - 68
Involvement of alpha5beta1 integrins in interleukin 8 production induced by oral viridans streptococcal protein I/IIf in cultured endothelial cells; Al-Okla S et al.; Using human endothelial cells, we define a mechanism that accounts for the induction of interleukin 8 (IL-8) by protein I/IIf, an adhesin from Streptococcus mutans serotype f . We report that protein I/IIf interactions with endothelial cells increased the tyrosine phosphorylation of three cellular components with relative mass of 145,000, 125,000 and 70,000 in endothelial cells . These proteins were identified as phospholipase Cgamma (PLCy), focal adhesion kinase (FAK) and paxillin after immunoprecipitation with monoclonal antibodies (mAbs) and immunoblotting with antiphosphotyrosine mAbs . These results suggested that beta1 integrins could be one of the components implicated in the modulin activity of protein I/IIf . By incubating protein I/IIf with either purified alpha5beta1 integrins or with alpha5beta1 integrins overexpressing CHO cells, we demonstrated that alpha5beta1 integrins act as cell receptors for protein I/IIf . We also showed that protein I/IIf interactions with alpha5beta1 integrins lead to IL-8 secretion . Using specific inhibitors, we demonstrated that protein I/IIf-induced IL-8 release involves mitogen-activated protein kinases (MAPKs), and that PLCgamma and PKC also seem to contribute to protein I/IIf stimulation . However, PI-3K activation is not involved in IL-8 release . Altogether, these results indicate that, after binding to alpha5beta1 integrins, protein I/IIf induces IL-8 release by activating the MAPKs signalling pathways.

Genome Biol . 2000;1(6):RESEARCH0011 . Epub 2000 Dec 04.
Evidence for symmetric chromosomal inversions around the replication origin in bacteria; Eisen JA et al.; BACKGROUND: Whole-genome comparisons can provide great insight into many aspects of biology . Until recently, however, comparisons were mainly possible only between distantly related species . Complete genome sequences are now becoming available from multiple sets of closely related strains or species . RESULTS: By comparing the recently completed genome sequences of Vibrio cholerae, Streptococcus pneumoniae and Mycobacterium tuberculosis to those of closely related species - Escherichia coli, Streptococcus pyogenes and Mycobacterium leprae, respectively - we have identified an unusual and previously unobserved feature of bacterial genome structure . Scatterplots of the conserved sequences (both DNA and protein) between each pair of species produce a distinct X-shaped pattern, which we call an X-alignment . The key feature of these alignments is that they have symmetry around the replication origin and terminus; that is, the distance of a particular conserved feature (DNA or protein) from the replication origin (or terminus) is conserved between closely related pairs of species . Statistically significant X-alignments are also found within some genomes, indicating that there is symmetry about the replication origin for paralogous features as well . CONCLUSIONS: The most likely mechanism of generation of X-alignments involves large chromosomal inversions that reverse the genomic sequence symmetrically around the origin of replication . The finding of these X-alignments between many pairs of species suggests that chromosomal inversions around the origin are a common feature of bacterial genome evolution.

Oncol Rep, 2001 Mar-Apr, 8(2), 245 - 8
Presence of Streptococcus infection in extra-oropharyngeal head and neck squamous cell carcinoma and its implication in carcinogenesis; Shiga K et al.; To investigate the involvement of S . anginosus infection in head and neck cancer in the extra-oropharyngeal cavity, we analyzed 3 DNA samples prepared from squamous cell carcinoma of the external auditory canal and one from squamous cell carcinoma of the skin using polymerase chain reaction (PCR) analysis and Southern blot analysis to detect the DNA sequence of S . anginosus . We also examined these four specimens by Gram's stain to detect the streptococcal bacterial bodies . By PCR analysis, the DNA sequence of S . anginosus was found in 4 out of 4 (100%) DNA samples obtained from these tumors . By Southern blot analysis, positive bands were detected in one out of the 3 (33%) samples from the tumor taken from the external auditory canal . We detected streptococcal bacterial bodies in one of the three specimens from the tumor obtained from cancer of the external auditory canal and in the one specimen from the skin cancer by the method of Gram's stain . Contrary to our expectations, these bacterial bodies were located in the middle of the tumor . Since S . anginosus is thought to exist in the mouth as a normal flora and to be located mainly in the gingiva and dental plaque, these data strongly indicate that S . anginosus infection is implicated in the carcinogenesis of head and neck squamous cell carcinoma.

Antimicrob Agents Chemother, 2001 Mar, 45(3), 952 - 5
New mutation in parE in a pneumococcal in vitro mutant resistant to fluoroquinolones; Janoir C et al.; For an in vitro mutant of Streptococcus pneumoniae selected on moxifloxacin four- to eightfold-increased MICs of new fluoroquinolones, only a twofold-increased MIC of ciprofloxacin, and a twofold-decreased MIC of novobiocin were observed . This phenotype was conferred by two mutations: Ser81Phe in GyrA and a novel undescribed His103Tyr mutation in ParE, outside the quinolone resistance-determining region, in the putative ATP-binding site of topoisomerase IV.

Antimicrob Agents Chemother, 2001 Mar, 45(3), 938 - 42
In vitro development of resistance to six quinolones in Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus; Boos M et al.; Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus isolates were exposed to subinhibitory MICs of ciprofloxacin, sparfloxacin, gatifloxacin, moxifloxacin, clinafloxacin, and gemifloxacin during a 10-day period . Subculturing led to resistance development, regardless of the initial potencies of the quinolones . None of the quinolones was associated with a significantly slower rate of resistance development.

Antimicrob Agents Chemother, 2001 Mar, 45(3), 805 - 9
Amino acid repetitions in the dihydropteroate synthase of Streptococcus pneumoniae lead to sulfonamide resistance with limited effects on substrate K(m); Haasum Y et al.; Sulfonamide resistance in Streptococcus pneumoniae is due to changes in the chromosomal folP (sulA) gene coding for dihydropteroate synthase (DHPS) . The first reported laboratory-selected sulfonamide-resistant S . pneumoniae isolate had a 6-bp repetition, the sul-d mutation, leading to a repetition of the amino acids Ile(66) and Glu(67) in the gene product DHPS . More recently, clinical isolates showing this and other repetitions have been reported . WA-5, a clinical isolate from Washington State, contains a 6-bp repetition in the folP gene, identical to the sul-d mutation . The repetition was deleted by site-directed mutagenesis . Enzyme kinetic measurements showed that the deletion was associated with a 35-fold difference in K(i) for sulfathiazole but changed the K(m) for p-aminobenzoic acid only 2.5-fold and did not significantly change the K(m) for 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine pyrophosphate . The enzyme characteristics of the deletion variant were identical to those of DHPS from a sulfonamide-susceptible strain . DHPS from clinical isolates with repetitions of Ser(61) had very similar enzyme characteristics to the DHPS from WA-5 . The results confirm that the repetitions are sufficient for development of a resistant enzyme and suggest that the fitness cost to the organism of developing resistance may be very low.

Antimicrob Agents Chemother, 2001 Mar, 45(3), 794 - 9
Streptococcus pneumoniae response to repeated moxifloxacin or levofloxacin exposure in a rabbit tissue cage model; Xuan D et al.; The role of moxifloxacin and levofloxacin pharmacokinetics (PK) in antimicrobial efficacy and in the selection of fluoroquinolone-resistant Streptococcus pneumoniae strains was investigated using the rabbit tissue cage abscess model . A rabbit tissue cage was created by insertion of sterile Wiffle balls in the dorsal cervical area . Animals orally received a range of moxifloxacin or levofloxacin doses that simulate human PK for 7 days 48 h after the Wiffle balls were inoculated with fluoroquinolone-sensitive S . pneumoniae (10(7) CFU) . Abscess fluid was collected on a daily basis over 14 days to measure bacterial density and MICs . Moxifloxacin regimens produced a range of area under the concentration-time curve (AUC)/MIC ratios ranging from 9.2 to 444 and peak/MIC ratios ranging from 1.3 to 102 . Levofloxacin doses produced AUC/MIC ratios of 5.1 to 85.5 and peak/MIC ratio of 0.9 to 14.8 . Moxifloxacin at 6.5, 26, and 42 mg/kg reduced the bacterial log CFU per milliliter in abscess fluid (percentage of that in a sterile animal) by 4.2 +/- 2.2 (20%), 5.8 +/- 0.4 (100%), and 5.4 +/- 0.4 (100%), respectively, over the dosing period . Levofloxacin at 5.5, 22, and 32 mg/kg reduced the log CFU per milliliter in abscess fluid (percentage of that in a sterile animal) by 2.8 +/- 0.7 (20%), 5.1 +/- 1.3 (80%), and 4.6 +/- 1.3 (60%), respectively . Moxifloxacin has a greater bactericidal rate as determined by regression of log CFU versus time data . The AUC/MIC and peak/MIC ratios correlated with the efficacy of both drugs (P < 0.05) . Resistance to either drug did not develop with any of the doses as assessed by a change in the MIC . In conclusion, data derived from this study show that moxifloxacin and levofloxacin exhibit rapid bactericidal activity against S . pneumoniae in vivo, and moxifloxacin exhibits enhanced bactericidal activity compared to levofloxacin, with AUC/MIC and peak/MIC ratios correlated with antimicrobial efficacy for both drugs . The development of fluoroquinolone-resistant S . pneumoniae was not observed with either drug in this model.

Antimicrob Agents Chemother, 2001 Mar, 45(3), 706 - 9
Activity of oritavancin (LY333328), an investigational glycopeptide, compared to that of vancomycin against multidrug-resistant Streptococcus pneumoniae in an in vitro pharmacodynamic model; Coyle EA et al.; In the past 2 decades, multidrug-resistant Streptococcus pneumoniae has been encountered with increasing frequency around the world . This has led to the need for newer agents in the treatment of S . pneumoniae infections . Oritavancin (LY333328) is a new glycopeptide antibiotic with activity against gram-positive organisms; however, there is limited information on the pharmacodynamics of oritavancin with respect to the treatment of S . pneumoniae . We utilized an in vitro pharmacodynamic model to compare the activity of oritavancin to that of vancomycin against two penicillin-, macrolide-, and ciprofloxacin-resistant S . pneumoniae isolates (R919 and R921) over a 48-h period . Both oritavancin and vancomycin achieved 99.9% (3-log) kill, with oritavancin achieving the limit of detection (10(2) CFU/ml) within 1 h and vancomycin achieving this limit at 24 h for both isolates . Detection of resistance was not observed for oritavancin or vancomycin during the 48-h experiments . The key pharmacodynamic parameter for oritavancin has not been well defined . In our experiment, the ratios of the area under the curve from 0 to 24 h to the MIC of oritavancin, oritavancin plus albumin, and vancomycin for both isolates were greater than 944.5, and the ratios of the maximum concentration of drug in serum to the MIC ranged from 73.7 to 7188.5 . T>MIC was 100% for oritavancin and vancomycin for both isolates . Oritavancin is a unique and potent antimicrobial that warrants further investigation against multidrug-resistant S . pneumoniae.

Antimicrob Agents Chemother, 2001 Mar, 45(3), 673 - 8
Comparative bactericidal activities of ciprofloxacin, clinafloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin against Streptococcus pneumoniae in a dynamic in vitro model; Klepser ME et al.; Several new quinolones that exhibit enhanced in vitro activity against Streptococcus pneumoniae have been developed . Using a dynamic in vitro model, we generated time-kill data for ciprofloxacin, clinafloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin against three isolates of quinolone-susceptible S . pneumoniae . Three pharmacokinetic profiles were simulated for each of the study agents (0.1, 1, and 10 times the area under the concentration-time curve {AUC}) . Target 24-h AUCs were based upon human pharmacokinetic data resulting from the maximal daily doses of each agent . Ciprofloxacin was the least active agent against all three isolates . With regimens that simulated the human 24-h AUC, ciprofloxacin resulted in an initial, modest decline in the numbers of CFU per milliliter; however, by 48 h the numbers of CFU per milliliter returned to or exceeded the starting inoculum . At the AUC, levofloxacin resulted in variable bacteriostatic and bactericidal activities against the isolates . The remaining agents yielded bactericidal (99.9% reduction) activity by 48 h with regimens that simulated the AUC . At 0.1 time the AUC ciprofloxacin and levofloxacin produced no inhibitory effect, grepafloxacin exhibited bacteriostatic activity, trovafloxacin had mixed static and cidal activities, and clinafloxacin and moxifloxacin caused significant reductions in the numbers of CFU per milliliter by 48 h . All six agents produced cidal activity at 10 times the AUC . In this dynamic in vitro model of infection, the quinolones demonstrated various degrees of activity against S . pneumoniae . The rank order of activity, with respect to bactericidal effect, was ciprofloxacin (least active) << levofloxacin < grepafloxacin, trovafloxacin < clinafloxacin and moxifloxacin (most active) . The rank order of the agents with respect to the selection of resistance was ciprofloxacin (most likely) > grepafloxacin, moxifloxacin, and trovafloxacin > levofloxacin > clinafloxacin.

An Esp Pediatr, 2001 Feb, 54(2), 160 - 4
{Vertically transmitted bacteremias: to treat or not to treat?}; Lopez Almaraz R et al.; OBJECTIVE . To analyze the incidence, etiology and management of infants born in 1977 with vertically transmitted bacteremia or suspected early neonatal sepsis . PATIENTS AND METHODS . The total number of newborn infants in this period was 2,365 . We revised the clinical histories of the infants diagnosed with bacteremia and classified them into two groups: a) those with vertically transmitted bacteremias, according to the recommendations of the Castrillo Group, and b) those with suspected early onset neonatal sepsis in whom blood culture was positive and analytical data suggested bacterial infection but who showed no clinical symptoms of vertically transmitted sepsis . Birthweight, sex, gestational age, risk factors for neonatal infection, clinical signs and laboratory tests suggestive of bacterial infection and microbiological agents were analyzed . The clinical and analytical evolution of the treated and untreated newborn infants was studied . RESULTS . The newborn infants were diagnosed with vertically transmitted bacteremia (an incidence of 4.2x1,000 live newborn infants) and 17 were diagnosed with suspected early onset neonatal sepsis (7.8x1,000 live newborns) . All the infants had risk factors for neonatal sepsis . The most common of them was prolonged membrane rupture (>- 18 hours) due to which sepsis screening was carried out (hemogram, C-reactive protein at 12 and 36-48 hours of life, and blood culture) . In both groups the most commonly isolated microorganism was group B streptococcus, which was found in 30% of vertically transmitted bacteremias and in 41.2% of suspected early onset neonatal sepsis . All the newborn infants with suspected sepsis and two with vertically transmitted bacteremia were treated without incident . The remaining eight infants with untreated vertically transmitted bacteremia were followed-up clinically ana analytically for one year, and remained asymptomatic . CONCLUSIONS . The most common microorganism in vertically transmitted bacteremia and suspected early onset neonatal sepsis was group B streptococcus . None of the untreated infants developed late sepsis or meningitis . Our findings suggest that non-treatment of asymptomatic infants with vertically transmitted bacteremias is appropriate as long and close clinical surveillance is maintained.

J Infect Dis, 2001 Mar 1, 183(5), 827 - 30 Epub 2001 Jan 25.
Protection against bacteremic pneumococcal infection by antibody to pneumolysin; Musher DM et al.; Pneumolysin is an important virulence factor of Streptococcus pneumoniae . This study examined the hypothesis that human antibody to pneumolysin provides protection against pneumococcal infection . At the time of hospital admission, patients with nonbacteremic pneumococcal pneumonia had higher levels of serum anti-pneumolysin IgG than did patients with bacteremic pneumococcal pneumonia or uninfected control subjects . IgG levels rose significantly during convalescence in patients with bacteremic pneumonia, reaching levels observed in nonbacteremic patients . Purified human anti-pneumolysin IgG protected mice against intraperitoneal challenge with S . pneumoniae types 1 or 4 in a dose-related fashion; mice that received anti-pneumolysin IgG had a greater likelihood of surviving challenge and had negative blood cultures . Pneumolysin damages epithelial cells and inhibits phagocytic function of polymorphonuclear leukocytes . One hypothesis that might explain the study results is that, early in infection, IgG to pneumolysin blocks these effects in the alveoli, thereby protecting the host against bacteremic pneumococcal disease.

J Infect Dis, 2001 Mar 1, 183(5), 823 - 6 Epub 2001 Jan 29.
Protective immunity to Streptococcus mutans induced by nasal vaccination with surface protein antigen and mutant cholera toxin adjuvant; Saito M et al.; In this study, mice were immunized nasally with surface protein antigen of Streptococcus mutans serotype c (PAc) and a nontoxic A subunit mutant of cholera toxin (mCT) E112K, as a mucosal adjuvant . Immunization with PAc and mCT elicited significant PAc-specific secretory IgA in saliva and in nasal secretions . Antibody-forming cell (AFC) analysis confirmed the antibody (Ab) titers by revealing significant numbers of PAc-specific IgA AFCs in the submandibular gland and nasal passages . Furthermore, CD4(+) T cells from cervical lymph nodes exhibited significant proliferative responses when restimulated with PAc in vitro . Importantly, mice that were nasally immunized with PAc plus mCT E112K exhibited significantly reduced oral colonization by S . mutans . These results show that nasal administration of PAc and mCT E112K is potentially an effective mucosal vaccine against dental caries and reduces the colonization of S . mutans in the oral cavity.

Clin Infect Dis, 2001 Feb 15, 32(4), 552 - 8 Epub 2001 Feb 09.
Clinical isolates of Streptococcus pneumoniae that exhibit tolerance of vancomycin; Henriques Normark B et al.; The ability of Streptococcus pneumoniae to escape lysis and killing by vancomycin, a property termed "tolerance," has recently been noted in a laboratory strain of the species . Vancomycin tolerance in clinical isolates represents a potential new health risk . We determined the prevalence of vancomycin and penicillin tolerance among 116 clinical isolates of pneumococci by monitoring lysis and viability after exposure to the respective antibiotic for 4 hours . Eight percent of the strains were tolerant to penicillin and 3% were tolerant to vancomycin . The 3 vancomycin-tolerant isolates also had a high ratio of minimum bactericidal concentration to minimum inhibitory concentration, in contrast to nontolerant strains . They were of serotype 9V and had reduced susceptibility to penicillin . Only 1 was also tolerant to penicillin . Growth rate and ability to divide were not affected in the 3 vancomycin-tolerant strains, and they all lysed with deoxycholate, which indicates autolysin production . Vancomycin tolerance among clinical isolates of pneumococci will necessitate tracking to determine the magnitude of the evolving health risk, since tolerance may contribute to treatment failure (in particular, cases of meningitis, in which bactericidal activity is critical for eradication) and since it may also be a favored background for acquisition of resistance of vancomycin.

Clin Infect Dis, 2001 Feb 15, 32(4), 534 - 8 Epub 2001 Feb 09.
Nonspecificity of assaying for IgG antibody to pneumolysin in circulating immune complexes as a means to diagnose pneumococcal pneumonia; Musher DM et al.; Detection of immunoglobulin G (IgG) antibody to pneumolysin (PLY) in precipitated circulating immune complexes (CICs) has been used to diagnose pneumococcal pneumonia . With care to include appropriate controls, we precipitated and dissociated CICs and then assayed for IgG antibody to PLY . We detected IgG antibody to PLY in CICs that were precipitated from serum samples that were obtained at the time of admission to the hospital from 5 (23%) of 22 healthy adults, 7 (44%) of 16 subjects with stable chronic obstructive pulmonary disease, 10 (63%) of 16 subjects colonized with Streptococcus pneumoniae, and 9 (60%) of 15 patients with nonbacteremic pneumococcal pneumonia . Of the 16 patients with bacteremic pneumococcal pneumonia, 4 (25%) had IgG antibody to PLY at the time of admission, and 8 (50%) had IgG antibody to PLY in convalescence . Levels of IgG antibody in CICs closely correlated with serum levels of IgG antibody to PLY, implicating precipitation of free serum antibody in tests with false-positive results . Detection of IgG antibody to PLY in precipitated CICs is not a reliable method for diagnosing pneumococcal pneumonia.

FEMS Microbiol Lett, 2001 Feb 20, 195(2), 139 - 44
Effect of amino acid substitutions in conserved residues in the leader peptide on biosynthesis of the lantibiotic mutacin II; Chen P et al.; The lantibiotic mutacin II, produced by Streptococcus mutans T8, is a ribosomally synthesized peptide antibiotic that contains thioether amino acids such as lanthionine and methyllanthionine as a result of post-translational modifications . The mutacin II leader peptide sequence shares a number of identical amino acid residues with class AII lantibiotic leader peptides . To study the role of these conservative residues in the production of active antimicrobial mutacin, 15 mutations were generated by site-directed mutagenesis . The effects of these substitutions vary from no effect to complete block-out . Mutations G-1A, G-2A, I-4D, and L-7K completely blocked the production of mature mutacin . Other mutations (I-4V, L-7M, E-8D, S-11T/A, V-12I/A, and E-13D) had no detectable effect on mutacin production . The changes of Glu-8 to Lys, Val-12 to Leu, Glu-13 to Lys reduced the mutacin production level to about 75%, 50%, and 10% of the wild-type, respectively . Thus, our data indicated that some of these conserved residues are essential for the mutacin biosynthesis, whereas others are important for optimal biosynthesis rates.

Infect Immun, 2001 Mar, 69(3), 1961 - 6
Selection of virulence-associated determinants of Streptococcus suis serotype 2 by in vivo complementation; Smith HE et al.; Within Streptococcus suis serotype 2, pathogenic, weakly pathogenic, and nonpathogenic strains can be found . We introduced a genomic library of a pathogenic strain into a weakly pathogenic strain . After infection of the library into young piglets pathogenic transformants were selected . One specific transformant containing a 3-kb fragment of the pathogenic strain appeared to be dominantly enriched in diseased pigs . The observed enrichment was not tissue specific . The selected fragment, when introduced into two different weakly pathogenic strains, increased the virulence of these strains considerably . In contrast, introduction of the corresponding fragment of a weakly pathogenic strain had only minor effects on virulence . Nucleotide sequence analysis of the selected fragment of the pathogenic strain revealed the presence of two potential open reading frames, both of which were found to be mutated in the corresponding fragment of the weakly pathogenic strain . These data strongly suggest that the selected fragment contains determinants important for virulence.

Infect Immun, 2001 Mar, 69(3), 1914 - 6
Regulation of matrix metalloproteinase expression in endothelial cells by heat-inactivated Streptococcus pneumoniae; Michel U et al.; Matrix metalloproteinases (MMPs) may contribute to an impaired endothelial layer in several diseases . We examined the effect of heat-inactivated Streptococcus pneumoniae R6 on MMP-2 and MMP-9 release by cultured aortic and brain capillary endothelial cells . Treatment with heat-inactivated S . pneumoniae caused an increased release of MMP-2 by both cell types.

Infect Immun, 2001 Mar, 69(3), 1729 - 38
Identification and characterization of a second extracellular collagen-like protein made by group A Streptococcus: control of production at the level of translation; Lukomski S et al.; A recent study found that group A Streptococcus (GAS) expresses a cell surface protein with similarity to human collagen (S . Lukomski, K . Nakashima, I . Abdi, V . J . Cipriano, R . M . Ireland, S . R . Reid, G . G . Adams, and J . M . Musser, Infect . Immun . 68:6542-6553, 2000) . This streptococcal collagen-like protein (Scl) contains a long region of Gly-X-X motifs and was produced by serotype M1 GAS strains . In the present study, a second member of the scl gene family was identified and designated scl2 . The Scl2 protein also has a collagen-like region, which in M1 strains is composed of 38 contiguous Gly-X-X triplet motifs . The scl2 gene was present in all 50 genetically diverse GAS strains studied . The Scl2 protein is highly polymorphic, and the number of Gly-X-X motifs in the 50 strains studied ranged from 31 in one serotype M1 strain to 79 in serotype M28 and M77 isolates . The scl1 and scl2 genes were simultaneously transcribed in the exponential phase, and the Scl proteins were also produced . Scl1 and Scl2 were identified in a cell-associated form and free in culture supernatants . Production of Scl1 is regulated by Mga, a positive transcriptional regulator that controls expression of several GAS virulence factors . In contrast, production of Scl2 is controlled at the level of translation by variation in the number of short-sequence pentanucleotide repeats (CAAAA) located immediately downstream of the GTG (Val) start codon . Control of protein production by this molecular mechanism has not been identified previously in GAS . Together, the data indicate that GAS simultaneously produces two extracellular human collagen-like proteins in a regulated fashion.

Infect Immun, 2001 Mar, 69(3), 1593 - 8
Use of a whole genome approach to identify vaccine molecules affording protection against Streptococcus pneumoniae infection; Wizemann TM et al.; Microbial targets for protective humoral immunity are typically surface-localized proteins and contain common sequence motifs related to their secretion or surface binding . Exploiting the whole genome sequence of the human bacterial pathogen Streptococcus pneumoniae, we identified 130 open reading frames encoding proteins with secretion motifs or similarity to predicted virulence factors . Mice were immunized with 108 of these proteins, and 6 conferred protection against disseminated S . pneumoniae infection . Flow cytometry confirmed the surface localization of several of these targets . Each of the six protective antigens showed broad strain distribution and immunogenicity during human infection . Our results validate the use of a genomic approach for the identification of novel microbial targets that elicit a protective immune response . These new antigens may play a role in the development of improved vaccines against S . pneumoniae.

Biochem Biophys Res Commun, 2001 Feb 16, 281(1), 37 - 44
Essential role of domain 4 of pneumolysin from Streptococcus pneumoniae in cytolytic activity as determined by truncated proteins; Baba H et al.; Pneumolysin (PLY), an important virulence factor of Streptococcus pneumoniae, is one of the members of thiol-activated cytolysins (TACYs) consisting of four domains . TACYs commonly bind to membrane cholesterol and oligomerize to form transmembrane pore . We have constructed full-length and various truncated PLYs to study the role of domains of PLY in the cytolytic activity . Full-length PLY had binding ability to both cell membrane and immobilized cholesterol . A truncated PLY which comprised only domain 4 molecule, the C-terminal domain of PLY, sustained the binding ability to cell membrane and cholesterol, whereas domain 1-3 molecule had no binding ability to them . Furthermore, the domain 4 molecule inhibited both the membrane binding and the hemolytic activity of full-length PLY . Accordingly, the present results provided the direct evidence that domain 4 was essential for the initial binding to membrane cholesterol and the interaction led to the subsequent membrane damage process.

Curr Infect Dis Rep, 2001 Feb, 3(1), 20 - 28
Quinolone Resistance: Older Concepts and Newer Developments; Bast DJ et al.; New quinolone compounds have been recommended for use in the treatment of respiratory tract infections, particularly pneumonia caused by multi drug-resistant Streptococcus pneumoniae . Of concern, however, is the recent emergence of pneumococcal isolates with reduced susceptibilities to both old and new quinolone compounds . This necessitates the employment of quinolone-use strategies aimed at restricting the emergence of resistance, to extend the effectiveness of this very important class of antibacterial agents . This article provides a comprehensive review of the recent discoveries in type II topoisomerase/quinolone structure-function relationships . It also addresses new insights into the mechanisms of quinolone resistance, the predicted trends in quinolone resistance, and possible strategies for quinolone use against S . pneumoniae.

Curr Infect Dis Rep, 2001 Feb, 3(1), 9 - 12
Relationship of Penicillin Resistance to Mortality in Pneumococcal Pneumonia; Mandell LA; Clinical management of community-acquired pneumonia (CAP)--and Streptococcus pneumoniae infection in general--are controversial . Multiple sets of guidlines exist . This article reviews CAP, S . pneumoniae infection and drug resistance, the four sets of guidlines currently in use in North America, and the data upon which the agencies establishing those guidlines have based their consclusions, particularly about drug resistance and treatment failures . The article also considers the role of penicillin in the treatment of pneumococcal pneumonia.

Pediatr Infect Dis J, 2001 Jan, 20(1), 85 - 7
Pneumococcal pyomyositis; Breton JR et al.; Pyomyositis is most commonly caused by Staphylococcus aureus . A 25-month-old child developed infection of the biceps brachialis muscle caused by Streptococcus pneumoniae . The child had no underlying immune or anatomic defect.

Pediatr Infect Dis J, 2001 Jan, 20(1), 34 - 9
Acute otitis media caused by Streptococcus pneumoniae in children's hospitals between 1994 and 1997; Wald ER et al.; OBJECTIVE: To determine patterns of resistance for isolates of Streptococcus pneumoniae recovered from middle ear fluids of children from eight children's hospitals between September, 1994, and August, 1997 . METHODS: Data were extracted retrospectively from the medical records of eight children's hospitals . A standardized data form was completed for each episode of pneumococcal infection . Systemic isolates (blood and pleural, synovial and spinal fluids) of S . pneumoniae were collected during the same period . All isolates of S . pneumoniae from each center were sent to a central laboratory . Susceptibility to penicillin and ceftriaxone was determined by microbroth dilution . Organisms were considered nonsusceptible to penicillin if the minimum inhibitory concentration was > or = 0.1 microg/ml and nonsusceptible to ceftriaxone if the minimum inhibitory concentration was > or = 1.0 microg/ml . RESULTS: S . pneumoniae was recovered from the middle ear fluids of 707 children from all centers during the study period . Thirty-nine (5.5%) were infections recorded at 4 centers which evaluated middle ear fluid only sporadically and were not included in this analysis . The remaining 668 infections reported by the 4 remaining participating hospitals reflect the experience of 608 children . There were 54% boys; 440 (73%) were Caucasian, 111 (18%) were African-American, 38 (6%) were Hispanic and for 19 (3%) the race was not recorded . The children ranged in age from 16 days to 13.8 years with a mean (+/-sD) of 26.0 (+/- 26.1) months . Children who received antibiotics in the 30 days before the middle ear isolate was recovered were more likely to harbor a resistant strain of S . pneumoniae than children who had not recently received an antibiotic (P < 0.001) . Isolates recovered from children with spontaneous otorrhea were more likely to be susceptible to penicillin than isolates recovered during myringotomy, with or without the insertion of tympanostomy tubes (P < 0.01) . There was wide variation in the susceptibility of middle ear isolates to penicillin and ceftriaxone according to geographic location; however, in every locale the middle ear isolates were less likely to be susceptible to penicillin and ceftriaxone than systemic isolates of S . pneumoniae . CONCLUSION: The prevalence of penicillin-resistant and cephalosporin-resistant S . pneumoniae in middle ear isolates derived from children cared for at four different children's hospitals was quite variable . In some locations the prevalence of resistance is still increasing, whereas in other areas the rate of resistance was at a plateau during the period of surveillance . The prevalence of isolates of S . pneumoniae susceptible to penicillin and ceftriaxone was always less common among middle ear isolates than among systemic isolates . Previous antibiotic use remains the most predictive factor for the recovery of isolates resistant to penicillin and ceftriaxone.

Chemotherapy, 2001 Mar-Apr, 47(2), 110 - 6
Patterns of antibiotic resistance, serotype distribution, and patient demographics of Streptococcus pneumoniae in Hong Kong; Ip M et al.; Streptococcus pneumoniae isolates from clinical specimens during the period 1993-1997 at the Prince of Wales Hospital, Hong Kong, were analysed by the antibiotic resistance profiles, the distribution of serotypes, specimen types, and patient demographics . 1,229 non-duplicate S . pneumoniae isolates were evaluated; 84% from the respiratory tract, 11% from blood and cerebrospinal fluid and the remainder from body fluids and pus swabs . The percentage of S . pneumoniae of reduced penicillin susceptibility was 38.6%, and the percentage resistance to erythromycin, chloramphenicol, co-trimoxazole and tetracycline were 40.4, 43.2, 54.9 and 77.8%, respectively . The organism was isolated from patients of all age groups, 14.6% from children aged below 10 years, half of whom were from children aged 2 years or below . 57.0% were from elderly patients aged above 60 . The male to female ratio was 2.5:1 . Isolates with reduced penicillin susceptibility were seen significantly more so in children under 10 than in those aged 11 or above (52 versus 36%, p < 0.0001) . A diverse range of serotypes was obtained in the penicillin-susceptible isolates whilst those of reduced susceptibility were confined to serotypes 23F, 19F, 6B, 14 and 9V .

Chemotherapy, 2001 Mar-Apr, 47(2), 104 - 9
In vitro activity of gemifloxacin against Streptococcus pneumoniae isolates in Germany; Lemmen S et al.; The MICs (minimal inhibitory concentrations) of gemifloxacin, moxifloxacin, ofloxacin, ciprofloxacin, levofloxacin, sparfloxacin, penicillin G, tetracycline and erythromycin were determined for 200 clinical pneumococcal isolates using the microbroth dilution method . MIC(50) and MIC(90) values were as follows (mg/l): 0.016 and 0.016 (gemifloxacin, penicillin-intermediate strains), 0.03 and 0.06 (gemifloxacin, penicillin-susceptible strains); 0.125-0.5 and 0.25 (moxifloxcacin); 1-2 and 4 (ciprofloxacin and ofloxacin); 1 and 2 (levofloxacin), and 0.25-0.5 and 0.5 (sparfloxacin) . MIC(50) and MIC(90) values for the fluoroquinolones were nearly identical for individual antimicrobial agents in the penicillin-susceptible and penicillin-intermediate groups of strains . Erythromycin and tetracycline were less active against penicillin-intermediate pneumococci isolates (erythromycin: MIC(90) 8 mg/l; MIC range 0.06-> or =64 mg/l; tetracycline: MIC(90) > or =64 mg/l, MIC range 0.25- > or =64 mg/l) as compared to penicillin-susceptible isolates (erythromycin: MIC(90) 0.5 mg/l, MIC range 0.06-> or =64 mg/l; tetracycline: MIC(90) 8 mg/l, MIC range 0.06-> or =64 mg/l) .

Curr Opin Microbiol, 2001 Feb, 4(1), 71 - 7
Streptococcus pneumoniae: new tools for an old pathogen; Hollingshead SK et al.; The pneumococcus is one of the longest-known pathogens . It has been instrumental to our understanding of biology in many ways, such as in the discovery of the Gram strain and the identification of nucleic acid as the hereditary material . Despite major advances in our understanding of pneumococcal pathogenesis, the need for vaccines and antibiotics to combat this pathogen is still vital . Genomics is beginning to uncover new virulence factors to advance this process, and it is enabling the development of DNA chip technology, which will permit the analysis of gene expression in specific tissues and in virulence regulatory circuits.

Curr Opin Microbiol, 2001 Feb, 4(1), 65 - 70
Toward a genome-scale understanding of group A Streptococcus pathogenesis; Graham MR et al.; Recent significant contributions have been made to the understanding of Group A Streptococcus (GAS) pathogenesis . New regulatory pathways have been discovered, insight into the molecular basis of epidemics of serotype M1 disease has been obtained, the crystal structures of four toxins have been reported and a genome sequence of one GAS strain has been determined . Genome-scale approaches to the study of GAS pathogenesis are now rapidly emerging and will advance our fundamental understanding of the molecular basis of host-pathogen interactions.

J Infect Dis, 2001 Feb 15, 183(4), 670 - 4 Epub 2001 Jan 24.
Characterization of consecutive Streptococcus pyogenes isolates from patients with pharyngitis and bacteriological treatment failure: special reference to prtF1 and sic / drs; Brandt CM et al.; To analyze bacteriological treatment failure in streptococcal pharyngitis, 40 consecutive Streptococcus pyogenes isolates from 18 patients were characterized . For 17 patients, isolates were indistinguishable with respect to emm type, random amplified polymorphic DNA pattern, and presence of prtF1 encoding the fibronectin-binding protein F1 . prtF1 was detected only in the 11 isolates (4 patients) with emm12 and in the single isolate with emm6 . Further analysis by vir(mga) regulon typing, sequencing of sic encoding the streptococcal inhibitor of complement from 19 isolates with emm1 (9 patients), and sequencing of drs (distantly related sic) from 11 isolates with emm12 revealed distinct sic alleles with insertions and/or deletions in sic that corresponded to differences in restriction patterns of the vir(mga) regulon only for paired isolates of 2 patients . Among isolates with emm12, 2 novel drs alleles were found . Analysis of these data suggests that neither the presence of prtF1 nor the diversification of sic / drs is required for the persistence of S . pyogenes in pharyngitis.

J Infect Dis, 2001 Feb 15, 183(4), 633 - 9 Epub 2001 Jan 17.
Distribution of streptococcal inhibitor of complement variants in pharyngitis and invasive isolates in an epidemic of serotype M1 group A Streptococcus infection; Hoe NP et al.; Streptococcal inhibitor of complement (Sic) is a highly polymorphic extracellular protein made predominantly by serotype M1 group A Streptococcus (GAS) . New variants of the Sic protein frequently appear in M1 epidemics as a result of positive natural selection . To gain further understanding of the molecular basis of M1 epidemics, the sic gene was sequenced from 471 pharyngitis and 127 pyogenic and blood isolates recovered from 598 patients living in metropolitan Helsinki, Finland, during a 37-month population-based surveillance study . Most M1 GAS subclones recovered from pyogenic infections and blood were abundantly represented in the pool of subclones causing pharyngitis . Alleles shared among the pharyngitis, pyogenic, and blood samples were identified in throat isolates a mean of 9.8 months before their recovery from pyogenic infections and blood, which indicates that selection of most sic variants occurs on mucosal surfaces . In contrast, no variation was identified in the emm and covR/covS genes.

Clin Infect Dis, 2001 Jan 15, 32(2), E24 - 30 Epub 2001 Jan 15.
Opsonization of T1M1 group A Streptococcus: dynamics of antibody production and strain specificity; Eriksson BK et al.; A chemiluminescence method was used to study opsonization of group A Streptococcus (GAS) of serotype T1M1 in serum samples ("sera") obtained from Swedish patients with invasive and noninvasive GAS infection and from healthy blood donors . Acute-phase serum samples ("acute sera") generally demonstrated low ability to opsonize the patient's own GAS isolate, regardless of clinical manifestation . Only approximately 15% of serum samples obtained from healthy blood donors demonstrated high opsonic activity against a standard T1M1 strain . Opsonization of 62 T1M1 isolates (obtained during 1980-1998) by a single immune serum sample showed considerable variation; this indicates that high opsonic immunity may develop only against the infecting isolate or identical clones . T1M1 GAS isolated from 1987 through 1990 were better opsonized by the immune serum sample than were isolates obtained before 1987 or after 1990, a finding that suggests a temporal change of the surface properties that affect opsonization.

Oral Microbiol Immunol, 2001 Feb, 16(1), 40 - 4
The effect of amino acid spacers on the antigenicity of dimeric peptide--inducing cross-reacting antibodies to a cell surface protein antigen of Streptococcus mutans; Oishi Y et al.; In the course of developing a synthetic peptide vaccine for dental caries, we identified a unique 13-mer peptide named PAc(365-377), TYEAALKQYEADL, as a minimum peptide inducing cross-inhibiting antibodies to a cell surface protein antigen (PAc) of Streptococcus mutans . However, the peptide could hardly induce the production of antibody in the absence of adjuvant . Thus using this peptide as a unit peptide, tandem constructs of dimeric unit peptide with or without spacer amino acid residues were synthesized, and their antigenicities were examined in B10.D2 mice . Significant augmentation of antigenicity was obtained in all of the dimeric unit peptides with spacers, especially for lysine spacers . In addition, analysis for cross-reactivity of anti-construct antibodies against a set of double valine-substituted analogues of the unit peptide revealed that the di-lysine spacer might be more effective in inducing the cross-reacting antibodies to rPAc.

Oral Microbiol Immunol, 2001 Feb, 16(1), 34 - 9
The time-course of acid excretion, levels of fluorescence dependent on cellular nicotinamide adenine nucleotide and glycolytic intermediates of Streptococcus mutans cells exposed and not exposed to air in the presence of glucose and sorbitol; Iwami Y et al.; The aim of this study was to examine glucose and sorbitol metabolism in Streptococcus mutans cells exposed and not exposed to air at the coexistence of these compounds by measuring acid excretion, levels of fluorescence dependent on cellular NADH and glycolytic intermediates . An aliquot of bacterial cells grown under strictly anaerobic conditions (anaerobic cells) was exposed temporarily to air (aerobic cells) . When glucose was added to the anaerobic cells metabolizing sorbitol, the acid excretion was increased . The level of NADH decreased initially and then increased to the higher plateau level than that during glucose metabolism . The aerobic cells neither metabolized sorbitol nor contained glycolytic intermediates . However, 2 min after glucose was added in the presence of sorbitol, the acid excretion was started slowly and the intermediates appeared . The level of NADH was decreased at first and then increased . These results suggested that the anaerobic S . mutans cells metabolized glucose and sorbitol simultaneously, and that in the presence of sorbitol the aerobic cells could start to metabolize glucose 2 min after glucose was added, as the intermediates (phosphoenopyruvate potential) for the glucose transport were accumulated.

Immunology, 2001 Jan, 102(1), 67 - 76
Adjuvant effects of CpG oligodeoxynucleotides on responses against T-independent type 2 antigens; Kovarik J et al.; Oligodeoxynucleotides containing CpG motifs (CpG-ODN) are potent in vitro B-cell activators and they have been successfully used to increase in vivo antibody responses to T-dependent peptide and protein antigens . In contrast, the use of CpG-ODN to enhance in vivo antibody responses to various T-independent type 2 (TI-2) antigens has recently generated contradictory results . In this study, we compared the CpG-ODN stimulatory effect on antibody responses of adult and young BALB/c mice to trinitrophenylaminoethyl-carboxymethyl (TNP) -Ficoll and to polysaccharides (PS) from several distinct serotypes of Streptococcus pneumoniae (SPn) . CpG-ODN co-administration significantly enhanced antigen-specific immunoglobulin M (IgM), IgG, IgG1 and IgG2a titres to TNP-Ficoll . The depletion of CD4+ cells by monoclonal antibodies (GK1.5) identified their essential role in CpG-ODN-mediated enhancement of antibody responses . In contrast to TNP-Ficoll, CpG-ODN failed to enhance IgM and IgG responses to any of the 18 SPnPS serotypes tested . Providing T-cell epitopes by the conjugation of SPnPS to the carrier protein tetanus toxoid again allowed CpG-ODN to mediate enhancement of IgG, IgG2a and IgG3 responses to most SPnPS serotypes . Thus, antigen-presenting cell/T-cell interaction appears to largely mediate the in vivo influence of CpG-ODN on antibody responses to TI-2 antigens . In early life, additional factors limit CpG-ODN modulation of antibody responses to TI-2 antigens.

Clin Microbiol Infect, 2000 Jun, 6(6), 308 - 15
Evolution of Streptococcus pneumoniae serotypes and antibiotic resistance in Belgium-update (1994-98); Verhaegen J et al.; OBJECTIVE: To follow the evolution of capsular types and resistance of Streptococcus pneumoniae, isolated from deep sites . METHODS: More than 100 Belgian laboratories permanently collect S . pneumoniae strains isolated from puncture specimens (blood, cerebrospinal fluid, middle ear fluid, etc.) and forward them to the reference center in Leuven, in order to determine the capsular serogroups and types (SGTs) and their resistance . RESULTS: From 1994 to 1998, the 5486 S . pneumoniae strains examined belonged to 39 of the 46 currently identified SGTs . The 10 most frequent SGTs accounted for 78.9% of the isolates, and 97% of all isolates belonged to SGTs included in the 23-valent vaccine . Overall mortality of patients with pneumococcal bacteremia or meningitis was 9.7%, and 23.8% in patients over 80 years . From 1994 to 1998, resistance to penicillin (P) increased from 7.6% to 14.2%, to tetracycline (T) from 14.9% to 28.0%, and to erythromycin (E) from 22.9% to 31% . Triple resistance (PTE) increased from 0.9% in 1994 to 6.6% in 1998 . Five SGTs (6, 9, 14, 19 and 23) accounted for 50% of the isolates, but for > 90% of the penicillin-resistant or erythromycin-resistant isolates . CONCLUSIONS: Resistance of S . pneumoniae to penicillin, erythromycin and tetracycline is steadily increasing and is concentrated in five serotypes included in the 23-valent pneumococcal vaccine . Increasing resistance and high mortality of invasive infections are an incentive to vaccinate vulnerable groups.

Clin Microbiol Infect, 2000 Feb, 6(2), 69 - 73
Pneumococcal acute otitis media in children; Kouppari G et al.; OBJECTIVES: To evaluate the clinical and laboratory findings of Streptococcus pneumoniae acute otitis media in children during a 1 year period . METHODS: From October 1995 to September 1996, 113 children aged 2 months to 14 years (median 18 months), with S . pneumoniae acute otitis media were studied . Susceptibility testing was performed by the Kirby-Bauer method and the E-test, and serotyping by the Quellung reaction . RESULTS: E-test assays detected five isolates (4.4%) to be highly resistant to penicillin and 13 (11.5%) that had intermediate resistance . All isolates were found to be susceptible to vancomycin, rifampicin and cefotaxime . In total, 25 isolates (22.1%) were resistant to one or more drugs . Fifty per cent of the penicillin-resistant or intermediately resistant S . pneumoniae isolates were resistant to multiple drugs, whereas only 2.1% of the penicillin-susceptible isolates were resistant to multiple drugs . The predominating serogroups of the isolates with reduced susceptibility to penicillin were the 19 (61.1%), 9 (16.7%), 23 (11.1%), 6 (5.5%) and 14 (5.5%) whereas those of the susceptible isolates were the 19 (26.3%), 14 (13.7%), 3 (11.6%), 6 (11.6%), 9 (8.4%), 1 (5.3%) and 12 (5.3%) . CONCLUSIONS: Streptococcus pneumoniae isolates from children with acute otitis media were penicillin-insensitive in 15.9% . The multiresistant S . pneumoniae isolates belonged to serogroups: 19 (45.4%), 9 (27.3%), 6 (18.2%) and 23 (9.1%).

Clin Microbiol Infect, 2000 Jan, 6(1), 2 - 8
Pharyngeal colonization prevalence rates for Streptococcus pyogenes and Streptococcus pneumoniae in a respiratory chemoprophylaxis intervention study using azithromycin; Putnam SD et al.; OBJECTIVES: A prospective assessment of the pharyngeal colonization prevalence rates for Streptococcus pyogenes and Streptococcus pneumoniae before and after an azithromycin chemoprophylaxis intervention clinical trial in a cohort of US Marine Corps trainees . In addition, the minimum inhibitory concentrations (MICs) for all streptococcal isolates, for azithromycin, penicillin, erythromycin and cefotaxime are reported . METHODS: Between November 1994 and March 1995, 1108 asymptomatic male US Marine Corps trainees, located in Southern California, were randomly assigned to one of three intervention groups: (1) weekly oral azithromycin, 500 mg (n = 362); (2) 1.2 MU benzathine penicillin G, intramuscularly once (n = 374); or (3) no chemoprophylaxis (n = 372) . Subjects provided both a pre- and post-training pharyngeal culture and microbial analysis was conducted to determine the colonization status of each study subject . RESULTS: The pretraining colonization prevalence was 1.2% for S . pneumoniae and 2.4% for S . pyogenes . There was no statistical difference in pretraining prevalence between the three treatment groups for either organism . Post-training pharyngeal cultures revealed an overall prevalence of 1.1% with no difference between treatment arms . However, the overall post-training prevalence of S . pyogenes colonization increased to 4.8%, with the azithromycin group having significant evidence of protection (0.7%) in comparison with the no-treatment group (8.2%) . The Etest method demonstrated no significant difference in the MIC50, MIC90, and MIC ranges between pre- and post-training isolates for any of the tested drugs . CONCLUSION: The use of azithromycin as a chemoprophylactic agent to reduce the colonization and subsequent infection of streptococcal respiratory disease among healthy adult male military recruits may be beneficial.

APMIS, 2000 Jul-Aug, 108(7-8), 473 - 81
Synthesis and antibacterial properties of peptidyl derivatives and cyclopeptides structurally based upon the inhibitory centre of human cystatin C . Dissociation of antiproteolytic and antibacterial effects; Kasprzykowski F et al.; Cysteine protease-inhibiting proteins of the cystatin superfamily can inhibit the replication of certain viruses and bacteria . The inhibitory centre of human cystatin C, the most widely distributed human cystatin, comprises three peptide segments . The present work describes the synthesis and antibacterial activity of 27 new peptidyl derivatives or cyclopeptides based upon the aminoterminal segment Arg8-Leu9-Val10-Gly11 . Fourteen of the new compounds displayed antibacterial activity against from 1 up to 9 of 17 clinically important bacterial species tested . Antiproteolytic activity of a compound was usually not required for its antibacterial capacity . Peptidyl diazomethanes generally had a very narrow antibacterial spectrum, inhibiting only Streptococcus pyogenes, whereas cyclopeptides and peptidyl derivatives of the general structure X-Arg-Leu-NH-CH(iPr)-CH2-NH-Y had a much wider spectrum . The most potent of these substances displayed approximately equal minimal inhibitory and bactericidal concentrations of about 20 microg/ml for both Staphylococcus aureus and S . pyogenes and were devoid of antiproteolytic activity . Several of the new substances could protect mice against lethal intraperitoneal challenge with S . pyogenes . Though their target remains to be disclosed, the group of substances here reported might be promising for the development of antibacterial drugs and the discovery of novel principles of action.

Vaccine, 2001 Feb 8, 19(13-14), 1717 - 26
A DNA vaccine encoding a peptide mimic of Streptococcus pneumoniae serotype 4 capsular polysaccharide induces specific anti-carbohydrate antibodies in Balb/c mice; Lesinski GB et al.; Streptococcus pneumoniae is a leading cause of morbidity and mortality in both the developing and developed world . The T-independent nature of the current polysaccharide vaccine renders it ineffective in elderly adults and children <2 years of age . Although the recently licensed conjugate vaccines are capable of producing T-cell-dependent immunity, they also have their limitations, namely a lack of response in certain populations . Our laboratory has focused on a different approach, DNA vaccination . We have defined a peptide sequence (pep4) that mimics the S . pneumoniae serotype 4 capsular polysaccharide (PPS4) using a monoclonal antibody to PPS4 (mAb4) and phage display library . Pep4 was synthesized, complexed to proteosomes and used to immunize mice . We have shown by ELISA that this peptide mimic is capable of eliciting an anti-PPS4 immune response significantly higher than in negative control mice (P<0.05) . A PPS4-DNA vaccine was made by cloning an oligodeoxynucleotide encoding pep4 into the HBcAg vector . Following epidermal immunization with the PPS4-DNA vaccine, mice produced an anti-PPS4 antibody response significantly higher than in mice immunized with an impertinent DNA vector (P<0.05) . Our results demonstrate the feasibility of peptide mimicry in DNA vaccine development.

Curr Biol, 2001 Jan 9, 11(1), R35 - 8
Polymeric Ig receptor: defender of the fort or Trojan horse?
Kaetzel CS.
The polymeric immunoglobulin receptor (pIgR) is important in host defense, transporting antibodies across mucosal epithelial cells . Recent work has shown that, using a protein that binds directly to the pIgR, Streptococcus pneumoniae can co-opt the transcytosis machinery and gain entry into airway epithelial cells.

Microbes Infect, 2000 Dec, 2(15), 1855 - 64
Mechanisms of antibiotic resistance and tolerance in Streptococcus pneumoniae; Charpentier E et al.; Streptococcus pneumoniae is a major pathogen causing potentially life-threatening community-acquired diseases in both the developed and developing world . Since 1967, there has been a dramatic increase in the incidence of penicillin-resistant and multiply antibiotic-resistant pneumococci worldwide . Prevention of access of the antibiotic to the target, inactivation of the antibiotic and alteration of the target are mechanisms that S . pneumoniae has developed to resist antibiotics . Recent studies on antibiotic-tolerant pneumococcal mutants permitted development of a novel model for the control of bacterial cell death.

Arch Oral Biol, 2001 Jan, 46(1), 49 - 55
Caries risk assessment from dental plaque and salivary Streptococcus mutans counts on two culture media; Sanchez-Perez L et al.; This study attempted to determine which combination of plaque or saliva, and tryptic soy agar, bacitracin (TSY20B) or mitis salivarius, bacitracin media, yielded the highest caries-predictive values for mutans counts in children with different caries prevalence . Sixty children were divided into three equally sized groups: caries free, low caries and high caries . Eighteen months later, their caries incidence and initial mutans count were compared . Fissure plaque on TSY20B yielded a high correlation between mutans counts and caries prevalence (P<0.009, r=3346) and incidence (P<0.003, r=4521) . The caries-predictive values obtained demonstrate that the coefficient of variation of mutans counts from lower first-molar fissure plaque on TSY20B accounts for 20.4% of the variation in final caries index . This strong correlation provides a valuable tool for the identification of caries-prone individuals.

Vaccine, 2000 Dec 8, 19 Suppl 1, S87 - 95
The potential for using protein vaccines to protect against otitis media caused by Streptococcus pneumoniae; Briles DE et al.; Potential vaccine strategies against otitis media are to prevent (1) symptomatic infections in the middle ear and/or (2) carriage of pneumococci and thereby subsequent middle ear infections . The possibility of using immunity to virulence proteins of pneumococci to elicit immunity against pneumococci has been examined . PspA has been found to have efficacy against otitis media in animals . Vaccination with a mixture of PsaA and PspA has been observed to offer better protection against nasal carriage in mice, than vaccination with either protein alone . PspA and pneumolysin have been shown to elicit protection against invasive infections . The inclusion of a few of these proteins into the polysaccharide-protein conjugate vaccines may be able to enhance their efficacy against otitis media and might be able to constitute a successful all-protein pneumococcal vaccine.

Arch Oral Biol, 2001 Feb, 46(2), 129 - 38
Selection of oral microbial adhesion antagonists using biotinylated Streptococcus sanguis and a human mixed oral microflora; Guan YH et al.; A microtitre assay has been developed using hydroxyapatite-coated wells and Streptococcus sanguis NCTC 10904 at 10(7) cells per ml . A number of models representing toothpaste and mouthwash usage were adopted to detect the anti-adherent efficacy of a polyvinylmethylether maleic acid copolymer (PVM/MA), polyoxypropylene/polyoxyethylene block copolymer (PO/EO), two casein-derived peptides and selected silicones . The results not only confirmed the anti-adherence property of the selected components but also indicated possible molecular interactions leading to the observed performance . To account for the diversity of oral microbial cells in vivo, a further testing system was developed . This involved submerging a hydroxyapatite disc in a mixed culture of human salivary microbial cells, and exposing it to different treatments using the active component either in an aqueous dispersion or in a toothpaste . The effect of toothpastes containing PO/EO, dimethicone copoyol or PVM/MA was investigated over a 4-h incubation with microflora . These tests showed that in a toothpaste formulation the anti-adherent efficacy may be reduced when compared with an aqueous dispersion containing the same or nearly the same concentration of the active component.

Cell, 2001 Jan 12, 104(1), 143 - 52
Cytolysin-mediated translocation (CMT): a functional equivalent of type III secretion in gram-positive bacteria; Madden JC et al.; Type III secretion for injection of effector proteins into host cells has not been described for Gram-positive bacteria despite their importance in disease . Here, we describe an injection pathway for the Gram-positive pathogen Streptococcus pyogenes that utilizes streptolysin O (SLO), a cholesterol-dependent cytolysin . The data support a model in which an effector is translocated through the SLO pore by a polarized process . The effector, SPN (S . pyogenes NAD-glycohydrolase), is capable of producing the potent second messenger cyclic ADP-ribose, and SLO and SPN act synergistically to trigger cytotoxicity . These data provide a novel paradigm for the function of the cholesterol-dependent cytolysin family and its wide distribution suggests that cytolysin-mediated translocation (CMT) may be the equivalent of type III secretion for Gram-positive pathogens.

Microb Pathog, 2001 Feb, 30(2), 71 - 9
Polymorphism of the virulence regulon and allelic variations of the sic gene among the emm1 isolates of group A Streptococcus from western Norway; Mylvaganam H et al.; With the objective of finding genetic markers of invasiveness, 43 isolates of group A streptococcus, isolated in western Norway and from both severe invasive disease and superficial infections, were studied initially by restriction fragment length polymorphism of the virulence regulon (virR -RFLP) . Polymorphism that seemed to be related to the severity of infection was observed within the emm1 sequence type, which included 11 invasive and seven non-invasive isolates . These emm1 isolates were further investigated by restriction mapping of the virR and sequence analysis of a polymorphic region, which revealed the presence of a hypervariable sic gene . Of the nine distinct sic alleles, seven were found in single isolates, of which only two were from patients with invasive disease . The other two alleles were shared among nine invasive and two non-invasive isolates . The presence of only two sic allotypes in nine of the 11 invasive isolates, as compared to a different allele in each of the five non-invasive, contemporary isolates supports the hypothesis that selection of the sic variants occurs at mucosal surfaces and implicates mainly two clones among the invasive emm1 isolates .

J Hand Surg {Br}, 2001 Feb, 26(1), 56 - 7
Streptococcus milleri infection; Lunn JV et al.; We report three cases of flexor sheath infection due to Streptococcus milleri in two patients . Soft tissue damage was extensive despite surgical debridement and appropriate antibiotic therapy . One patient had two digits amputated and the other had the affected digit amputated at the level of the proximal interphalangeal joint.These cases illustrate the potential pathogenicity of a bacterium which is often regarded as a commensal .

Microbiology, 2001 Jan, 147(Pt 1), 21 - 30
Competition among three predominant ruminal cellulolytic bacteria in the absence or presence of non-cellulolytic bacteria; Chen J et al.; Competition among three species of ruminal cellulolytic bacteria - Fibrobacter succinogenes S85, Ruminococcus flavefaciens FD-1 and Ruminococcus albus 7 - was studied in the presence or absence of the non-cellulolytic ruminal bacteria Selenomonas ruminantium or Streptococcus bovis . Co-cultures were grown under either batch or continuous conditions and populations were estimated using species-specific oligonucleotide probes to 16S rRNA . The three cellulolytic species co-existed in cellobiose batch co-culture, but inclusion of either Sel . ruminantium or Str . bovis yielded nearly a monoculture of the non-cellulolytic competitor . In cellobiose chemostats, R . albus completely dominated the triculture, but R . flavefaciens became predominant over F . succinogenes and R . albus when Sel . ruminantium was co-inoculated into the chemostats . Similar effects on competition were observed in the presence of Str . bovis at a lower (0.021 h(-1)), but not at a higher (0.045 h(-1)) dilution rate . In cellulose batch co-cultures, R . albus was more abundant than both F . succinogenes and R . flavefaciens, regardless of the presence of the non-cellulolytic species . Co-existence among the three cellulolytic species was observed in almost all cellulose chemostats, but Sel . ruminantium altered the relative proportions of the cellulolytic species . R . albus and R . flavefaciens were found to produce inhibitors that suppressed growth of R . flavefaciens and F . succinogenes, respectively . These data indicate that interactions among cellulolytic bacteria, while complex, can be modified further by non-cellulolytic species.

Infect Immun, 2001 Feb, 69(2), 1215 - 20
Restoration of Mga function to a Streptococcus pyogenes strain (M Type 50) that is virulent in mice; Limbago B et al.; The Mga protein in B514Sm, a Streptococcus pyogenes strain isolated as a mouse pathogen, contains amino acid substitutions at conserved sites that render the protein defective . Replacement of mga50 with the functional homolog mga4.1 restored full expression of Mga-regulated proteins . Restoration of Mga function did not affect fibrinogen binding, nor did it affect virulence in several mouse models of group A streptococcus infection.

Infect Immun, 2001 Feb, 69(2), 949 - 58
Identification and characterization of a novel family of pneumococcal proteins that are protective against sepsis; Adamou JE et al.; Four pneumococcal genes (phtA, phtB, phtD, and phtE) encoding a novel family of homologous proteins (32 to 87% identity) were identified from the Streptococcus pneumoniae genomic sequence . These open reading frames were selected as potential vaccine candidates based upon their possession of hydrophobic leader sequences which presumably target these proteins to the bacterial cell surface . Analysis of the deduced amino acid sequences of these gene products revealed the presence of a histidine triad motif (HxxHxH), termed Pht (pneumococcal histidine triad) that is conserved and repeated several times in each of the four proteins . The four pht genes (phtA, phtB, phtD, and a truncated version of phtE) were expressed in Escherichia coli . A flow cytometry-based assay confirmed that PhtA, PhtB, PhtD and, to a lesser extent, PhtE were detectable on the surface of intact bacteria . Recombinant PhtA, PhtB, and PhtD elicited protection against certain pneumococcal capsular types in a mouse model of systemic disease . These novel pneumococcal antigens may serve as effective vaccines against the most prevalent pneumococcal serotypes.

Infect Immun, 2001 Feb, 69(2), 924 - 30
Systemic and mucosal immunizations with fibronectin-binding protein FBP54 induce protective immune responses against Streptococcus pyogenes challenge in mice; Kawabata S et al.; The purpose of this study was to examine the suitability of fibronectin-binding protein FBP54 as a putative vaccine for Streptococcus pyogenes infections . When the distribution of the fbp54 gene among the clinical isolates representing various M serotypes was tested by PCR and Southern blot assays, it was found that all of the strains possess this gene . Furthermore, a significant increase in immunoglobulin G (IgG) antibody titers against FBP54 was observed in sera from patients with S . pyogenes infections compared with those from healthy volunteers (P < 0.005) . Mice were immunized with FBP54 subcutaneously, orally, or nasally . An enzyme-linked immunosorbent assay revealed that antigen-specific IgG antibodies were induced in the sera of immunized mice, while high salivary levels of IgA antibodies were detected after oral and nasal immunizations . Mice subcutaneously or orally immunized with FBP54 survived significantly longer following the challenge with S . pyogenes than did nonimmunized mice (P < 0.001) . These results indicate that FBP54 is a promising vaccine for the prevention of S . pyogenes infections.

Infect Immun, 2001 Feb, 69(2), 853 - 64
Combinatorial library cloning of human antibodies to Streptococcus pneumoniae capsular polysaccharides: variable region primary structures and evidence for somatic mutation of Fab fragments specific for capsular serotypes 6B, 14, and 23F; Lucas AH et al.; Antibodies specific for capsular polysaccharides play a central role in immunity to encapsulated Streptococcus pneumoniae, but little is known about their genetics or the variable (V) region polymorphisms that affect their protective function . To begin to address these issues, we used combinatorial library cloning to isolate pneumococcal polysaccharide (PPS)-specific Fab fragments from two vaccinated adults . We determined complete V region primary structures and performed antigen binding analyses of seven Fab fragments specific for PPS serotype 6B, 14, or 23F . Fabs were of the immunoglobulin G2 or A isotype . Several V(H)III gene segments (HV 3-7, 3-15, 3-23, and 3-11) were identified . V(L) regions were encoded by several kappa genes (KV 4-1, 3-15, 2-24, and 2D-29) and a lambda gene (LV 1-51) . Deviation of the V(H) and V(L) regions from their assigned germ line counterparts indicated that they were somatically mutated . Fabs of the same serotype specificity isolated from a single individual differed in affinity, and these differences could be accounted for either by the extent of mutation among clonal relatives or by usage of different V-region genes . Thus, functionally disparate anti-PPS antibodies can arise within individuals both by activation of independent clones and by intraclonal somatic mutation . For one pair of clonally related Fabs, the more extensively mutated V(H) was associated with lower affinity for PPS 14, a result suggesting that somatic mutation could lead to diminished protective efficacy . These findings indicate that the PPS repertoire in the adult derives from memory B-cell populations that have class switched and undergone extensive hypermutation.

Infect Immun, 2001 Feb, 69(2), 845 - 52
Pneumolysin is the main inducer of cytotoxicity to brain microvascular endothelial cells caused by Streptococcus pneumoniae; Zysk G et al.; In pneumococcal meningitis it is assumed that bacteria cross the blood-brain barrier (BBB), which consists mainly of cerebral endothelial cells . The effect of Streptococcus pneumoniae on the BBB was investigated with an in vitro BBB model using a human brain microvascular endothelial cell line (HBMEC) and primary cultures of bovine brain microvascular endothelial cells (BBMEC) . Within a few hours of incubation with pneumococci, rounding and detachment of the HBMEC were observed, and the transendothelial electrical resistance of the BBMEC monolayer decreased markedly . An S . pneumoniae mutant deficient in pneumolysin did not affect the integrity of the endothelial cell monolayer . Neither cell wall fragments nor isolated pneumococcal cell walls induced changes of endothelial cell morphology . However, purified pneumolysin caused endothelial cell damage comparable to that caused by the viable pneumococci . The cell detachment was dependent on de novo protein synthesis and required the activities of caspase and tyrosine kinases . The results show that pneumolysin is an important component for damaging the BBB and may contribute to the entry of pneumococci into the cerebral compartment and to the development of brain edema in pneumococcal meningitis.

Infect Immun, 2001 Feb, 69(2), 822 - 31
Identification of Rgg-regulated exoproteins of Streptococcus pyogenes; Chaussee MS et al.; Streptococcus pyogenes secretes many proteins that influence host-pathogen interactions . Despite their importance, relatively little is known about the regulation of these proteins . The rgg gene (also known as ropB) is required for the expression of streptococcal erythrogenic toxin B (SPE B), an extracellular cysteine protease that contributes to virulence . Proteomics was used to determine if rgg regulates the expression of additional exoproteins . Exponential- and stationary-phase culture supernatant proteins made by S . pyogenes NZ131 rgg and NZ131 speB were separated by two-dimensional electrophoresis . Differences were identified in supernatant proteins from both exponential- and stationary-phase cultures, although considerably more differences were detected among stationary-phase supernatant proteins . Forty-two proteins were identified by peptide fingerprinting with matrix-assisted laser desorption mass spectrometry . Mitogenic factor, DNA entry nuclease (open reading frame {ORF 226}), and ORF 953, which has no known function, were more abundant in the culture supernatants of the rgg mutant compared to the speB mutant . ClpB, lysozyme, and autolysin were detected in the culture supernatant of the speB mutant but not the rgg mutant . To determine if Rgg affected protein expression at the transcriptional level, real-time (TaqMan) reverse transcription (RT)-PCR was used to quantitate Rgg-regulated transcripts from NZ131 wild-type and speB and rgg mutant strains . The results obtained with RT-PCR correlated with the proteomic data . We conclude that Rgg regulates the transcription of several genes expressed primarily during the stationary phase of growth.

Infect Immun, 2001 Feb, 69(2), 787 - 93
Synthetic 6B di-, tri-, and tetrasaccharide-protein conjugates contain pneumococcal type 6A and 6B common and 6B-specific epitopes that elicit protective antibodies in mice; Jansen WT et al.; The immunogenicity and protective capacity of Streptococcus pneumoniae 6B capsular polysaccharide (PS)-derived synthetic phosphate-containing disaccharide (Rha-ribitol-P-), trisaccharide (ribitol-P-Gal-Glc-), and tetrasaccharide (Rha-ribitol-P-Gal-Glc-)-protein conjugates in rabbits and mice were studied . In rabbits, all saccharides conjugated to keyhole limpet hemocyanin (KLH) evoked high levels of pneumococcal (Pn) type 6B antibodies that facilitated type-specific phagocytosis . Unlike the disaccharide rabbit antisera, tri- and tetrasaccharide rabbit antisera also reacted with 6A PS in an enzyme-linked immunosorbent assay (ELISA) and promoted phagocytosis of 6A pneumococci . All these rabbit antisera passively protected mice against a Pn 6B challenge . The disaccharide conjugate-induced antiserum, however, failed to protect mice against a 6A challenge . In mice, phagocytic and protective anti-Pn 6B antibodies were only induced by the tetrasaccharide conjugate and not by PS 6B or PS 6B-protein conjugates . These antibodies did not cross-react with 6A PS in ELISA and were unable to phagocytize 6A pneumococci . In conclusion, the disaccharide and tetrasaccharide conjugates already contain epitopes capable of inducing 6B-specific, fully protective antibodies in rabbits and mice, respectively.

Infect Immun, 2001 Feb, 69(2), 751 - 7
Commercial preparations of lipoteichoic acid contain endotoxin that contributes to activation of mouse macrophages in vitro; Gao JJ et al.; Lipoteichoic acids (LTA), cell wall components of gram-positive bacteria, have been reported to induce various inflammatory mediators and to play a key role in gram-positive-microbe-mediated septic shock . In a large number of these studies, investigators used commercially available LTA purified from a variety of gram-positive bacteria, including Staphylococcus aureus, Bacillus subtilis, and Streptococcus sanguis . We report here that, although these commercially available LTA could be readily shown to stimulate production of nitric oxide (NO) in RAW 264.7 mouse macrophages, the activity was dramatically inhibited by polymyxin B, a relatively specific inhibitor of endotoxin biological activity . One-step purification of the commercially available S . aureus LTA using hydrophobic interaction chromatography resulted in two well-separated peak fractions, one highly enriched for LTA and a second highly enriched for endotoxin . The LTA-enriched fractions did not induce production of NO in RAW 264.7 macrophages, although they caused a dose-dependent induction of NO in the presence of low concentrations of gamma interferon (IFN-gamma) (which by itself induced little NO), regardless of the presence of polymyxin B . In contrast, the endotoxin-enriched fractions by themselves inhibited in high levels of NO in RAW 264.7 macrophages but activity was almost completely inhibited in the presence of polymyxin B . Consistent with these findings, our data also indicate that commercial LTA preparations from S . aureus, B . subtilis, and S . sanguis were not able to induce NO from lipopolysaccharide-hyporesponsive C3H/HeJ mouse peritoneal macrophages, but in the presence of IFN-gamma, these LTA preparations were able to induce relatively high levels of NO from C3H/HeJ macrophages . These results indicate that commercially available LTA can contain contaminating and potentially significant levels of endotoxin that can be expected to contribute to the putative macrophage-stimulating effects of LTA as assessed by NO production . The fact that the purified LTA, by itself, was not able to induce significant levels of NO secretion in RAW 264.7 macrophages supports the conclusion that caution in attributing high-level biological activity to this microbial cell wall constituent should be exercised.

Infect Immun, 2001 Feb, 69(2), 744 - 50
Interleukin-6 deficiency increases inflammatory bone destruction; Balto K et al.; Periapical bone destruction occurs as a consequence of pulpal infection . In previous studies, we showed that interleukin-1 (IL-1) is the primary stimulator of bone destruction in this model . IL-6 is a pleiotropic cytokine that is induced in these infections and has both pro- and anti-inflammatory activities . In the present study, we determined the role of IL-6 in regulating IL-1 expression and bone resorption . The first molars of IL-6 knockouts (IL-6(-/-)) and wild-type mice were subjected to surgical pulp exposure and infection with a mixture of four common pulpal pathogens, including Prevotella intermedia, Fusobacterium nucleatum, Peptostreptococcus micros, and Streptococcus intermedius . Mice were killed after 21 days, and bone destruction and cytokine expression were determined . Surprisingly, bone destruction was significantly increased in IL-6(-/-) mice versus that in wild-type mice (by 30%; P < 0.001) . In a second experiment, the effects of chronic (IL-6(-/-)) IL-6 deficiency and short-term IL-6 deficiency induced by in vivo antibody neutralization were determined . Both IL-6(-/-) (30%; P < 0.001) and anti-IL-6 antibody-treated mice (40%; P < 0.05) exhibited increased periapical bone resorption, compared to wild-type controls . The increased bone resorption in IL-6-deficient animals correlated with increases in osteoclast numbers, as well as with elevated expression of bone-resorptive cytokines IL-1alpha and IL-1beta, in periapical lesions and with decreased expression of the anti-inflammatory cytokine IL-10 . These data demonstrate that endogenous IL-6 expression has significant anti-inflammatory effects in modulating infection-stimulated bone destruction in vivo.

Antimicrob Agents Chemother, 2001 Feb, 45(2), 636 - 8
Mechanisms of macrolide resistance in clinical pneumococcal isolates in France; Fitoussi F et al.; The genetic basis of macrolide resistance was investigated in a collection of 48 genotypically unrelated clinical isolates of Streptococcus pneumoniae obtained between 1987 and 1997 in France . All strains were resistant to erythromycin, clindamycin, and streptogramin B, exhibiting a macrolide-lincosamide-streptogramin B resistance phenotype, and harbored the erm(B) gene . None of the strains carried the mef(A) or erm(A) subclass erm(TR) gene.

Antimicrob Agents Chemother, 2001 Feb, 45(2), 630 - 2
Macrolide resistance in Peptostreptococcus spp . mediated by ermTR: possible source of macrolide-lincosamide-streptogramin B resistance in Streptococcus pyogenes; Reig M et al.; Eighty percent (21 of 26) of macrolide-resistant Peptostreptococcus strains studied harbored the ermTR gene . This methyltransferase gene is also the most frequently found gene among macrolide-lincosamide-streptogramin B-resistant Streptococcus pyogenes strains . Transfer of the ermTR gene from Peptostreptococcus magnus to macrolide-susceptible S . pyogenes strains indicates that this resistance determinant may circulate among gram-positive aerobic and anaerobic species of the oropharyngeal bacterial flora.

Antimicrob Agents Chemother, 2001 Feb, 45(2), 627 - 9
Two-year surveillance of antibiotic resistance in Streptococcus pneumoniae in four African cities; Benbachir M et al.; Worldwide spread of antibiotic resistance in Streptococcus pneumoniae is a major problem . However, data from West and North African countries are scarce . To study the level of resistance and compare the situations in different cities, a prospective study was conducted in Abidjan (Ivory Coast), Casablanca (Morocco), Dakar (Senegal), and Tunis (Tunisia), from 1996 to 1997 . The resistances to eight antibiotics of 375 isolates were studied by E test, and the results were interpreted using the breakpoints recommended by the National Committee for Clinical Laboratory Standards . Overall, 30.4% of the isolates were nonsusceptible to penicillin G (25.6% were intermediate and 4.8% were resistant) . Amoxicillin (96.3% were susceptible) and parenteral third-generation cephalosporins (92.7%) were highly active . Resistance to chloramphenicol was detected in 8.6% of the isolates . High levels of resistance were noted for erythromycin (28%), tetracycline (38.3%), and cotrimoxazole (36.4%) . Resistance to rifampin was rare (2.1%) . There were significant differences in resistance rates between individual countries . Multiple resistance was more frequent in penicillin-nonsusceptible isolates than in penicillin-susceptible isolates . Recommendations for treatment could be generated from these results in each participating country.

Antimicrob Agents Chemother, 2001 Feb, 45(2), 433 - 8
Mutant prevention concentrations of fluoroquinolones for clinical isolates of Streptococcus pneumoniae; Blondeau JM et al.; The mutant prevention concentration (MPC) represents a threshold above which the selective proliferation of resistant mutants is expected to occur only rarely . A provisional MPC (MPC(pr)) was defined and measured for five fluoroquinolones with clinical isolates of Streptococcus pneumoniae . Based on their potential for restricting the selection of resistant mutants, the five fluoroquinolones, in descending order, were found to be moxifloxacin > trovafloxacin > gatifloxacin > grepafloxacin > levofloxacin . For several compounds, 90% of about 90 clinical isolates that lacked a known resistance mutation had a value of MPC(pr) that was close to or below the serum levels that could be attained with a dosing regimen recommended by the manufacturers . Since MPC(pr) overestimates MPC, these data identify moxifloxacin and gatifloxacin as good candidates for determining whether MPC(pr) can be used as a guide for choosing and eventually administering fluoroquinolones to significantly reduce the development of resistance.

Pediatr Res, 2001 Feb, 49(2), 181 - 8
Superoxide dismutase and catalase do not affect the pulmonary hypertensive response to group B streptococcus in the lamb; Carpenter D et al.; The purpose of this study was to determine whether treatment with conjugated antioxidant enzymes could attenuate or abolish pulmonary hypertension induced by group B streptococcus (GBS) . Lambs, 3-7 d old, were anesthetized and ventilated . Intravascular catheters were placed in the left ventricle, descending aorta, right atrium, and pulmonary artery for continuous monitoring of intravascular pressures . Cardiac output was measured with radiolabeled microspheres . Measurements were obtained at baseline and 15 and 60 min into a 60-min GBS infusion, and 60 min after GBS was stopped . Blood gas values were held constant and PaO(2) was maintained >100 mm Hg . The control group received saline vehicle only (n = 6), the GBS group received GBS infusion only (n = 9), the enzymes (ENZ) group received polyethylene glycol-superoxide dismutase (PEG-SOD) and polyethylene glycol-catalase (PEG-CAT) treatment only (n = 6), and the ENZ+GBS group received PEG-SOD and PEG-CAT then GBS (n = 9) . Plasma samples were obtained to confirm increased superoxide dismutase and catalase activities in the groups receiving enzymes . Compared with baseline, pulmonary vascular resistance increased by 119% and 101% at 15 min and 87% and 81% at 60 min in the GBS and ENZ+GBS groups, respectively . Sixty minutes after the termination of the GBS infusion, PVR returned to baseline in the GBS group but did not in the ENZ+GBS group . Enzyme infusions resulted in at least a ninefold increase in plasma enzyme activities . As opposed to previously published data from endotoxin models, PEG-CAT and PEG-SOD were ineffective in altering the GBS-induced pulmonary hypertensive response in this model . This suggests that acute administration of antioxidant enzymes may not be effective in ameliorating GBS-induced pulmonary hypertension.

Microbiology, 2001 Feb, 147(Pt 2), 431 - 8
Characterization of the Streptococcus pneumoniae NADH oxidase that is required for infection; Yu J et al.; Streptococcus pneumoniae is an important human pathogen capable of causing serious infections . NADH oxidase, a factor necessary for infection, was previously identified as part of a signature-tagged mutagenesis screen of a S . pneumoniae clinical isolate, 0100993 . The mutant, with a plasmid insertion disrupting the nox gene, was attenuated for virulence in a murine respiratory tract infection model . A complete refined nox deletion mutant was generated by allelic-replacement mutagenesis and found to be attenuated for virulence 10(5)-fold in the murine respiratory tract infection model and at least 10(4)-fold in a Mongolian gerbil otitis media infection model, confirming the importance of the NADH oxidase for both types of S . pneumoniae infection . NADH oxidase converts O(2) to H(2)O . If O(2) is not fully reduced, it can form superoxide anion (O2(-)) and hydrogen peroxide (H(2)O(2)), both of which can be toxic to cells . Bacterial cell extracts from the allelic-replacement mutant were found to lack NADH oxidase activity and the mutant was unable to grow exponentially under conditions of vigorous aeration . In contrast, the mutant displayed normal growth characteristics under conditions of limited aeration . The S . pneumoniae nox gene was cloned and expressed in E . coli . The purified His-tagged NADH oxidase was shown to oxidize NADH with a K:(m) of 32 microM, but was unable to oxidize NADPH . Oxidation of NADH was independent of exogenous FAD or FMN.

Microbiology, 2001 Feb, 147(Pt 2), 419 - 29
Streptococcus pyogenes sclB encodes a putative hypervariable surface protein with a collagen-like repetitive structure; Whatmore AM; Streptococcus pyogenes is the causative agent in a wide range of diseases of humans of varying severity . During a study scanning the genome sequence of a serotype M1 invasive isolate SF370 for novel surface proteins, an ORF, designated sclB, was identified . The putative protein encoded by sclB contains both a signal peptide and classic Gram-positive wall-associated sequences . Comparison of the sequences of this ORF with those from a number of unrelated isolates demonstrated that sclB encodes a putative surface protein with a variable N-terminal sequence followed by a variable length tract of collagen-like GXY(n) repeats . A further feature of sclB is the presence of CAAAA repeat tracts immediately downstream of the putative start codon . The number of these pentameric repeats varies from 4 to 15 between strains and variation in repeat number results in the predicted SclB protein being either in or out of frame relative to the start codon . These observations suggest that expression of this protein may be regulated at the translational level as a result of gain or loss of CAAAA repeats . While the function of SclB remains to be elucidated, an sclB-specific transcript was detected by RT-PCR during in vitro culture . Finally, it is shown that a second gene, sclA, potentially encoding a protein with a similar extensive collagen-like structure and variable N-terminal sequence, is present in all isolates of S . pyogenes tested to date . Thus S . pyogenes harbours a novel family of structurally related and surface-exposed proteins of potential importance in the pathogenic process.

Microbiology, 2001 Feb, 147(Pt 2), 271 - 80
Environmentally regulated genes of Streptococcus suis: identification by the use of iron-restricted conditions in vitro and by experimental infection of piglets; Smith HE et al.; The identification of environmentally regulated genes of Streptococcus suis by the use of iron-restricted conditions in vitro and by experimental infection of piglets is described . Eighteen unique iron-restriction-induced (iri) genes and 22 unique in-vivo-selected (ivs) genes of Strep . suis were found . None of the ivs genes was exclusively expressed in vivo . Four iri genes were identical to four clones selected in piglets . Two ivs genes were similar to genes for putative virulence factors . One of these ivs genes was identical to the epf gene of virulent Strep . suis serotype 2 strains and the other showed homology to a gene encoding a fibronectin-binding protein of Streptococcus gordonii . Two additional ivs genes showed homology to environmentally regulated genes previously identified by using an in vivo expression technology (IVET) selection system in other bacterial species . One of these showed similarity to the agrA gene of Staphylococcus aureus, a key locus involved in the regulation of numerous virulence proteins . The promoter selection system described in this paper has been successfully used for the identification of many environmentally regulated genes potentially involved in the pathogenesis of Strep . suis infections in piglets.

J Clin Microbiol, 2001 Feb, 39(2), 733 - 7
Surveillance of invasive Streptococcus pneumoniae infection in the province of Quebec, Canada, from 1996 to 1998: serotype distribution, Antimicrobial susceptibility, and clinical characteristics; Jette LP et al.; In the province of Quebec, Canada, from 1996 to 1998, 3,650 invasive Streptococcus pneumoniae infections were reported . A total of 1,354 isolates were serotyped and tested for antimicrobial susceptibility . The distribution of serotypes remained stable over the 3 years, with serotypes 14, 6B, 4, 9V, 23F, and 19F accounting for 61% of the isolates . Overall, 90% of isolates were included in the current 23-valent vaccine and 67% were included in the 7-valent conjugate vaccine . We were able to determine that resistance to penicillin and to other antibiotics is increasing.

J Clin Microbiol, 2001 Feb, 39(2), 445 - 53
Relatedness of Streptococcus suis isolates of various serotypes and clinical backgrounds as evaluated by macrorestriction analysis and expression of potential virulence traits; Allgaier A et al.; We evaluated the genetic diversity of Streptococcus suis isolates of different serotypes by macrorestriction analysis and elucidated possible relationships between the genetic background, expression of potential virulence traits, and source of isolation . Virulence traits included expression of serotype-specific polysaccharides, muramidase-released protein (MRP), extracellular protein factor (EF), hemolysin activity, and adherence to epithelial cells . Macrorestriction analysis of streptococcal DNA digested with restriction enzymes SmaI and ApaI allowed differentiation of single isolates that could be assigned to four major clusters, named A1, A2, B1, and B2 . Comparison of the genotypic and phenotypic features of the isolates with their source of isolation showed that (i) the S . suis population examined, which originated mainly from German pigs, exhibited a genetic diversity and phenotypic patterns comparable to those found for isolates from other European countries; (ii) certain phenotypic features, such as the presence of capsular antigens of serotypes 2, 1, and 9, expression of MRP and EF, and hemolysin activity (and in particular, combinations of these features), were strongly associated with the clinical background of meningitis and septicemia; and (iii) isolates from pigs with meningitis and septicemia showed a significantly higher degree of genetic homogeneity compared to that for isolates from pigs with pneumonia and healthy pigs . Since the former isolates are considered highly virulent, this supports the theory of a clonal relationship among highly virulent strains.

J Bacteriol, 2001 Feb, 183(4), 1175 - 83
Identification and molecular analysis of PcsB, a protein required for cell wall separation of group B streptococcus; Reinscheid DJ et al.; Group B streptococcus (GBS) is the leading cause of bacterial sepsis and meningitis in neonates . N-terminal sequencing of major proteins in the culture supernatant of a clinical isolate of GBS identified a protein of about 50 kDa which could be detected in all of 27 clinical isolates tested . The corresponding gene, designated pcsB, was isolated from a GBS cosmid library and subsequently sequenced . The deduced PcsB polypeptide consists of 447 amino acid residues (M(r), 46,754), carries a potential N-terminal signal peptide sequence of 25 amino acids, and shows significant similarity to open reading frames of unknown function from different organisms and to the murein hydrolase P45 from Listeria monocytogenes . Northern blot analysis revealed a monocistronic transcriptional organization for pcsB in GBS . Insertional inactivation of pcsB in the genome of GBS resulted in mutant strain Sep1 exhibiting a drastically reduced growth rate compared to the parental GBS strain and showing an increased susceptibility to osmotic pressure and to various antibiotics . Electron microscopic analysis of GBS mutant Sep1 revealed growth in clumps, cell separation in several planes, and multiple division septa within single cells . These data suggest a pivotal role of PcsB for cell division and antibiotic tolerance of GBS.

J Antimicrob Chemother, 2001 Feb, 47(2), 215 - 8
Antimicrobial resistance of Streptococcus pneumoniae isolates in 1999 and 2000 in Madrid, Spain: a multicentre surveillance study; Oteo J et al.; Resistance to first-line antimicrobial agents in Streptococcus pneumoniae is increasing worldwide and the new fluoroquinolones may provide a good alternative . The antimicrobial susceptibility to levofloxacin and 13 other antibiotics of 300 isolates of S . pneumoniae, isolated in the Madrid community in 1999 and 2000, was determined . A total of 65.6% of isolates were penicillin intermediate or resistant strains . A high percentage of resistance to macrolides, clindamycin, tetracycline and chloramphenicol was also observed, mainly in penicillin-resistant strains . All but one strain was susceptible to levofloxacin.

Chest, 2001 Jan, 119(1), 185 - 95
Oral moxifloxacin vs high-dosage amoxicillin in the treatment of mild-to-moderate, community-acquired, suspected pneumococcal pneumonia in adults; Petitpretz P et al.; STUDY OBJECTIVES: Comparison of the efficacy and safety of moxifloxacin vs amoxicillin for treatment of mild-to-moderate, suspected pneumococcal community-acquired pneumonia (CAP) in adult patients . DESIGN: Multinational, multicenter, double-blind, randomized study . SETTING: Eighty-two centers in 20 countries (Argentina, Brazil, Chile, Croatia, Czech Republic, Estonia, France, Hong Kong, Hungary, Lithuania, Mexico, Portugal, Russia, Slovenia, South Africa, Spain, Turkey, Ukraine, United Kingdom, and Uruguay) . PATIENTS: Four hundred eleven adults (inpatients or outpatients) with suspected pneumococcal CAP . INTERVENTIONS: Randomization 1:1 to moxifloxacin, 400 mg/d, or amoxicillin, 1,000 g tid, for 10 days . RESULTS: Primary efficacy parameter was clinical response, 3 to 5 days after therapy (end of therapy {EOT}) in the per protocol (PP) population (362 patients) . The clinical success rate in the PP population was 91.5% (moxifloxacin) and 89.7% (amoxicillin; two-sided 95% confidence interval, -4.2 to 7.8%) . The clinical cure rate in patients with proven pneumococcal pneumonia was similar in both treatment groups (87.8%) . The bacteriologic success rate in 136 bacteriologically evaluable patients at the EOT was 89.7% (moxifloxacin) and 82.4% (amoxicillin) . The bacteriologic success rate against Streptococcus pneumoniae was 89.6% (moxifloxacin) and 84.8% (amoxicillin) . The frequency of adverse events was comparable in both treatment groups . Digestive symptoms were the most common drug-related adverse events in both treatment groups . CONCLUSIONS: Moxifloxacin was statistically at least as effective as high-dose amoxicillin for treatment of mild-to-moderate, suspected pneumococcal CAP . Moxifloxacin may be an alternative for empiric CAP treatment, especially in areas where multidrug resistance in S pneumoniae is sufficiently prevalent to preclude routine penicillin.

Am J Kidney Dis . 2001 Feb;37(2):E15.
Renal transplantation after Streptococcus pneumoniae-associated hemolytic uremic syndrome; Krysan DJ et al.; Of the several causes of nondiarrheal hemolytic uremic syndrome (HUS), infection with Streptococcus pneumoniae is infrequent, but important, because of its unique pathogenesis . A comprehensive literature review found 37 well-documented cases of S pneumoniae-associated HUS (SP-HUS), only 2 of which progressed to end-stage renal disease (ESRD) . We report the third such child, and the first to receive a renal transplant following SP-HUS . Her course illustrates several unique characteristics of SP-HUS common to previous patients reported in the literature, including a greater duration of oligoanuria compared with cases not progressing to ESRD, the significant adverse effect of unwashed blood products, and a possible influence of female gender on outcome . Clinicians caring for children with SP-HUS should be aware of these differences and modify therapy appropriately to avoid known risk factors for poor outcome, specifically the use of unwashed blood products.

Appl Environ Microbiol, 2001 Feb, 67(2), 969 - 71
Production of capsular polysaccharide of Streptococcus pneumoniae type 14 and its purification by affinity chromatography; Suarez N et al.; We describe a rapid and efficient method for producing the capsular polysaccharide of Streptococcus pneumoniae by fermentation on tryptic soy broth and purification of this compound by using immobilized soybean lectin as an affinity adsorbent . In principle, the same strategy can be used to produce purified capsular polysaccharides from other streptococcal serotypes by selecting the appropriate lectin adsorbents.

Appl Environ Microbiol, 2001 Feb, 67(2), 808 - 13
Nisin resistance of Streptococcus bovis; Mantovani HC et al.; The growth of Streptococcus bovis JB1 was initially inhibited by nisin (1 microM), and nisin caused a more than 3-log decrease in viability . However, some of the cells survived, and these nisin-resistant cells grew as rapidly as untreated ones . To see if the nisin resistance was merely a selection, nisin-sensitive cells were obtained from agar plates lacking nisin . Results indicated that virtually any nisin-sensitive cell could become nisin-resistant if the ratio of nisin to cells was not too high and the incubation period was long enough . Isolates obtained from the rumen were initially nisin sensitive, but they also developed nisin resistance . Nisin-resistant cultures remained nisin resistant even if nisin was not present, but competition studies indicated that nisin-sensitive cells could eventually displace the resistant ones if nisin was not present . Nisin-sensitive, glucose-energized cells lost virtually all of their intracellular potassium if 1 microM nisin was added, but resistant cells retained potassium even after addition of 10 microM nisin . Nisin-resistant cells were less hydrophobic and more lysozyme-resistant than nisin-sensitive cells . Because the nisin-resistant cells bound less cytochrome c, it appeared that nisin was being excluded by a net positive (i.e., less negative) charge . Nisin-resistant cells had more lipoteichoic acid than nisin-sensitive cells, and deesterified lipoteichoic acids from nisin-resistant cells migrated more slowly through a polyacrylamide gel than those from nisin-sensitive cells . These results indicated that lipoteichoic acids could be modified to increase the resistance of S . bovis to nisin . S . bovis JB1 cultures were still sensitive to monensin, tetracycline, vancomycin, and bacitracin, but ampicillin resistance was 1,000-fold greater.

Aust N Z J Obstet Gynaecol, 1999 May, 39(2), 257 - 9
Streptococcus viridans intra-amniotic infection associated with antecedent cunnilingus; Gherman RB et al.; Introduction of bacteria into the amniotic cavity has been associated with oral sex through an ascending infectious route . Previous reports have implicated both Capnocytophaga and Fusobacterium nucleatum via this process . We report a case of Streptococcus viridans intra-amniotic infection occurring at 25 weeks' gestation . Patient questioning revealed a close temporal relationship between the onset of symptoms and previous episodes of cunnilingus . The diagnosis of subclinical bacterial colonization of the amniotic fluid should be considered in patients presenting with preterm labour and no apparent aetiology . A history of recent cunnilingus may be associated with the presence of Streptococcus viridans in the amniotic fluid.

J Med Microbiol, 2000 Apr, 49(4), 371 - 4
An outbreak of skin sepsis in abattoir workers caused by an 'unusual' strain of Streptococcus pyogenes; Phillips G et al.; An outbreak of indolent skin infections due to an 'unusual' serological type of Streptococcus pyogenes that lasted for 3 months and affected eight workers in an abattoir is described . The group A streptococcal (GAS) isolates were serotyped as M-type 59; however, they possessed a T-protein pattern (T5/27/44) that is not commonly associated with M-type 59 . Further genotypic characterisation studies revealed that all eight isolates were indistinguishable by pulsed-field gel electrophoresis (PFGE) and possessed the emm gene encoding for the M-type 59 . Once identified, and after a combination of penicillin treatment, exclusion of workers with lesions and reinforcement of standard hygiene precautions, no further cases developed . Although common in the 1970s and 1980s, streptococcal infections in this situation are now reported infrequently . This report serves to highlight the issues surrounding working practices in abattoirs.

J Med Microbiol, 2000 Apr, 49(4), 361 - 6
Clinical and microbiological epidemiology of Streptococcus pneumoniae bacteraemia; McKenzie H et al.; A survey of Streptococcus pneumoniae bacteraemia in the Grampian region of Scotland was carried out over a 2-year period . One hundred and four bacteraemic episodes were identified in 103 patients, an incidence of 9.8/100,000 population/year, and the mortality was 24% . Clinical information was abstracted from 92 sets of patient notes and 98 isolates of S . pneumoniae were available for further study . The incidence of S . pneumoniae bacteraemia was highest at the extremes of age and peaked at 78 cases/100,000 population/year in those over 80 years old . Many patients had predisposing conditions, of which chronic lung disease (23%), chronic alcohol abuse (10%) and malignant disease (10%) were the commonest . Age was the highest risk factor for mortality, with 20 of the 22 deaths in those over 65 years old . The commonest serotype of S . pneumoniae isolated was serotype 14 (23.5%) . Only one isolate (serotype 6A) showed intermediate resistance to penicillin, but 12 isolates (12.2%) were resistant to erythromycin . Nine of these 12 isolates were of serotype 14 and had MICs clustered in the range 12-24 mg/L . Examination of all serotype 14 isolates by pulsed-field gel electrophoresis (PFGE) showed the presence of two distinct genetic clusters, with all the erythromycin-resistant isolates in the same cluster . These isolates had similar PFGE profiles to erythromycin-resistant serotype 14 strains isolated elsewhere in the UK and they were positive for the mefE gene by PCR, confirming that resistance was of the M phenotype . The recent increase in erythromycin resistance in S . pneumoniae may be due, at least in part, to the spread of a serotype 14 clone of the M phenotype which appears to be an important cause of invasive disease.

J Immunol, 2000 Apr 15, 164(8), 4111 - 9
Autoreactive B cells escape clonal deletion by expressing multiple antigen receptors; Kenny JJ et al.; IgH and L chain transgenes encoding a phosphocholine (PC)-specific Ig receptor were introduced into recombinase-activating gene (Rag-2-/-) knockout mice . The PC-specific B cells that developed behaved like known autoreactive lymphocytes . They were 1) developmentally arrested in the bone marrow, 2) unable to secrete Ab, 3) able to escape clonal deletion and develop into B1 B cells in the peritoneal cavity, and 4) rescued by overexpression of bcl-2 . A second IgL chain was genetically introduced into Rag-2-/- knockout mice expressing the autoreactive PC-specific Ig receptor . These dual L chain-expressing mice had B cells in peripheral lymphoid organs that coexpressed both anti-PC Ab as well as Ab employing the second available L chain that does not generate an autoreactive PC-specific receptor . Coexpression of the additional Ig molecules rescued the autoreactive anti-PC B cells and relieved the functional anergy of the anti-PC-specific B cells, as demonstrated by detection of circulating autoreactive anti-PC-Abs . We call this novel mechanism by which autoreactive B cells can persist by compromising allelic exclusion receptor dilution . Rescue of autoreactive PC-specific B cells would be beneficial to the host because these Abs are vital for protection against pathogens such as Streptococcus pneumoniae.

Crit Care Med, 2000 Mar, 28(3), 692 - 7
Evaluation of antimicrobial treatment in mechanically ventilated patients with severe chronic obstructive pulmonary disease exacerbations; Ewig S et al.; OBJECTIVE: To study microbial and susceptibility patterns and antimicrobial treatment responses in patients with severe, acute exacerbations of chronic obstructive pulmonary disease requiring mechanical ventilation . DESIGN: Microbial investigation using tracheobronchial aspirates, bronchoscopy with a protected specimen brush, and bronchoalveolar lavage, as well as paired serologies . Evaluation of antimicrobial treatment by results of the initial investigation, susceptibility testing, and a repeated microbial investigation (tracheobronchial aspirates, bronchoscopy with a protected specimen brush, and bronchoalveolar lavage) after 72 hrs . SETTING: A respiratory intensive care unit of a 1,000-bed teaching hospital . PATIENTS: Fifty severely exacerbated and mechanically ventilated patients with chronic obstructive pulmonary disease . INTERVENTIONS: Initial empirical antimicrobial treatment according to clinical judgment . MEASUREMENTS AND MAIN RESULTS: Overall, 36 of 50 patients (72%) had evidence of a microbial origin . Community-acquired endogenous pathogens were present in 70% of patients, and Gram-negative enteric bacilli and Pseudomonas/Stenotrophomonas species were present in 30% . All five isolates of Streptococcus pneumoniae were resistant to penicillin (three intermediately and two highly), and three were resistant to multiple antibiotics . Pseudomonas species revealed multiresistance in four of nine isolates (44%), and Stenotrophomonas maltophilia revealed multiresistance in one of two isolates . Antimicrobial treatment was modified according to diagnostic results in 11 of 31 patients (36%) with potentially pathogenic microorganisms . In patients who underwent a repeat investigation after 72 hrs, 24% of the initially present and potentially pathogenic microorganisms persisted . Inappropriate initial antimicrobial therapy was associated significantly with bacterial persistence (p < .002) . CONCLUSIONS: Considering the diversity of microbial pathogens and the resistance rates especially to S . pneumoniae in this patient population, antimicrobial treatment should be based on the constant study of local microbial and susceptibility patterns along with routine microbial investigation of the individual patient.

Presse Med, 2000 Dec 2, 29(37), 2057 - 60
{Streptpcoccus pneumoniae: current status of its resistance to antibiotics}; Muller-Serieys C; A WORLDWIDE ISSUE: Streptococcus pneumoniae is an important pathogen implicated in many illnesses . The susceptibility of this bacteria has greatly changed since 1967 when it was the leading strain resistant to penicillin G . Since that time, the resistance of S . pneumoniae has become a worldwide problem leading to the development of schemes to monitor resistance in different countries . The analysis of these "observation" studies points out the wide variability of resistance to antibiotics depending on the concerned country and region . Amoxicillin, cefotaxim, the new fluoroquinolones and vancomycin have exhibited the best preservation of efficacy worldwide . RESISTANCE IN FRANCE: Pneumococcal resistance is high in France against penicillin, third-generation cephalosporins, and erythromycin . Resistance has however appeared to stabilize since 1997, with the exception of invasive strains which have shown a rising level of penicillin G resistance . A NEW THREAT: Several authors have reported that vancomycin-tolerant strains have a significant clinical importance and must be carefully monitored . Reasonable prescription of antibiotics appears to be more than ever necessary to reduce the selection pressure of antibiotics.

Dan Med Bull, 2000 Nov, 47(5), 313 - 27
The importance of pharmacodynamic properties in treatment of penicillin resistant Streptococcus pneumoniae; Knudsen JD; As a short resume, the major result according to each objective listed in chapter 1 will be repeated . 1 . Adjusting and characterisation of the mouse peritonitis model for studying the treatment of pneumococci . The mouse peritonitis model was adjusted to study pneumococci with serotypes of low virulence to mice, by supplementing the inoculum with 5 (vt/vol)% mucin . This made the infection lethal with inoculi of 10(6) cfu/ml that also made the study of a bacterial growth phase possible (Knudsen et al., I) . The immune modelling effect of mucin lasted less than four hours (chapter 2) . The experimental infection in the mice was studied during time; The highly reproducible bacterial growth-phase was characterised as exponential growth in approximately 16 h, followed by an stationary phase until approximately 24 h post-challenge . A decline phase, not very reproducible, was found after 24 h, and in this phase the mice were beyond therapeutic range (Knudsen et al., III) . The efficacy of treatment as effect on bacterial counts, was as good in the stationary phase as in the exponential phase (Knudsen et al., III) . The pharmacokinetic properties of penicillin were studied during the infection, the serum elimination was slower in severely ill, than in newly challenged and in healthy mice (Knudsen et al., III) . The survival of mice in this experimental model did not correlate with the decline in bacterial counts in blood or peritoneal cavity (Knudsen et al., III, den Hollander et al., V) . 2 . To compare the efficacy of antibiotics against pneumococci in vitro and in vivo A highly statistically significant correlation was found between determinations of effect in vitro (MIC's) and in vivo (ED50's) for penicillin and ten pneumococcal strains, and for four cephalosporins and three pneumococcal strains (Knudsen et al., I, II) . One cephalosporin, cefepime, was shown better in vivo than expected from the cumulated in vitro data from four other cephalosporins, but no explanation for that observation was found (Knudsen et al., II) . Working with an immunocompetent model, the killing of bacteria in vivo can not always be predicted from in vitro time kill curves, as the immune system will contribute to the bacterial killing,--a higher kill rate of penicillin on pneumococci was found in vivo as compared to in vitro (Knudsen et al., I, III) . The killing of pneumococci in different dosing regimens of azithromycin in mice, was not directly correlated to kill rate using the same concentration profiles in an advanced in vitro pharmacokinetic model; but the CMAX as the most important pharmacodynamic parameter for survival of mice was also the most important parameter for killing of bacteria in vitro (Hollander et al., V) . Doses of various antibiotics providing only a bacteriostatic in the mice, can be appropriate in the treatment of the lethal infection and providing survival of mice (Knudsen et al., III, den Hollander et al., V) . A regrowth of bacteria in-between active doses of drug could not be found in counts in vivo which can be attributed to the immune system of the mice . (Knudsen et al., III, den Hollander et al., V) . The favourable MIC's of teicoplanin, with MIC50 and MIC90 four times lower than of vancomycin for pneumococci, were not observed in vivo, as the ED50's 50% and 90% percentiles for teicoplanin were more than half of the values for vancomycin . This could be explained by the high degree of protein binding of teicoplanin in mouse serum . The use of mouse serum in the MIC determination instead of the traditionally used media, could give a better prediction of the efficacy in mice (Knudsen et al., VI) . 3 . The efficacy of beta-lactams against pneumococci The efficacy in vitro of penicillin and five cephalosporins against pneumococci with various susceptibilities was concentration independent above four times the MIC, and the killing was independent of the level for the MIC's and independent on which beta-lactams used, but depending on the strains tested (Knudsen et al., I, II) . The MIC's of five cephalosporins correlated positively and significantly to each other, and to MIC's of penicillin when strains with various susceptibilities were tested (Knudsen et al., II) . In vivo a significant correlation between the effective doses and the MIC's for beta-lactams was found within the range, where effective concentration are achievable (Knudsen et al., I, II) . In the study of pneumococci with various susceptibility to penicillin, it was found, that independent of the penicillin susceptibilities, the most important parameter for treatment with penicillin of pneumococci was the T > MIC (Knudsen et al., I) . Penicillin treatment of bacteria in different phases of growth in vivo, showed that the most important parameter for growth was the T > MIC, also in the stationary phase (Knudsen et al., III) . 4 . (ABSTRACT TRUNCATED)

Oral Microbiol Immunol, 2000 Apr, 15(2), 131 - 8
Salivary and serum antibody response to Streptococcus mutans antigens in humans; Chia JS et al.; Humoral immunity against Streptococcus mutans infection was analyzed in caries-active and caries-free young adults by immunoblotting . All volunteers from both groups had detectable salivary immunoglobulin A (IgA) and serum IgG antibodies, with similar profiles . They could be classified on the basis of relative intensity of the immunoblot bands into categories of high or low responders . Common protein antigens with molecular weight ranging from approximately 45 to 190 kDa could be found either extracellularly or associated with the cell wall of S . mutans cultured in vitro . The predominant reactive antigens recognized by both IgA and IgG were of proteins around 63 and 60 kDa . Detection of IgA antibodies to the various antigens of S . mutans in individual saliva samples did not always correlate with serum IgG antibody profiles . In addition, distinct bands, which reacted preferentially with either IgA or IgG, could be detected by antibodies from specific subjects . Differential reactivities of salivary IgA and serum IgG antibodies to two, cell-wall associated protein antigens around 33 and 36 kDa were found in caries-active and caries-free young adults; 30.8% of caries-free subjects and 12% of caries-active subjects (P < 0.01) exhibited detectable antibody response to these antigens . This difference was not attributable to variations in antibody levels, since antibody response to these proteins were still detectable in some caries-free but not caries-active individuals whose levels of antibodies to other antigens were low . Thus, a new antibody profile which correlates with dental caries disease activity has been identified in a selected population . Differences in mucosal and systemic immune responses to S . mutans seem to be both antigen and host dependent.

Oral Microbiol Immunol, 2000 Apr, 15(2), 124 - 30
Induction of secretory immunity with bioadhesive poly (D,L-lactide-co-glycolide) microparticles containing Streptococcus sobrinus glucosyltransferase; Smith DJ et al.; The effect of mucosal delivery of Streptococcus sobrinus glucosyltransferase (GTF) in bioadhesive poly (D,L-lactide-co-glycolide) (PLGA) microparticles on induction of salivary IgA and serum IgG antibody responses was measured in Sprague-Dawley rats . Preparations of GTF/PLGA/gelatin microparticles, or PLGA/gelatin microparticles or GTF in alum, were administered four times at weekly intervals by intranasal or intragastric routes . Two subcutaneous injections of GTF in PLGA/gelatin microparticles or in alum were given to separate groups of rats . Significant elevations in salivary IgA antibody levels to S . sobrinus GTF were observed only in the groups immunized intranasally 28 days after immunizations were begun . Five of six rats given the GTF microparticles intranasally had positive salivary IgA antibody responses to GTF, and the mean salivary IgA antibody level of this group was 30-fold higher than any other mucosally or systemically immunized group . Salivary IgA responses in the GTF-microparticle group remained significantly higher than all other mucosally immunized groups for at least 10 weeks after the primary immunization . All rats in this group demonstrated aspects of anamnesis following a more limited secondary course of intranasal administration . Intranasal administration of GTF in microparticles also induced a serum IgG response to GTF in some rats . After secondary intranasal GTF microparticle administration, several rats had sustained serum IgG antibody levels that were within the range of sera from rats subcutaneously injected with GTF in microparticles or in alum . Thus intranasal delivery of GTF-containing bioadhesive microparticles induced the highest and longest lasting salivary immune response of any mucosal or systemic route or vehicle tested and could be expected to be a useful method for induction of mucosal immunity.

Oral Microbiol Immunol, 2000 Feb, 15(1), 58 - 62
Molecular cloning, sequence and characterization of a novel streptococcal phosphoglycerate dehydrogenase gene; Kawabata S et al.; The nucleotide sequence of a Streptococcus mutans serA gene that encodes D-3-phosphoglycerate dehydrogenase has been determined . The gene consisted of 1308-bp nucleotides coding for a 436-amino-acid polypeptide (48,546 Da) . The deduced amino acid sequence showed a 66% identity with SerA from Bacillus subtilis and possessed specific residues (G-R-P-N-V-G) in the coenzyme-binding domain, alpha B helix . Recombinant streptococcal SerA was expressed using pMAL-c2 expression vector and purified by amylose resin affinity chromatography and DEAE-Sephacel column chromatography . This SerA enzyme catalyzed detectable reduction of alpha-ketoglutarate to 2-hydroxyglutaric acid . These findings indicate that the novel streptococcal phosphoglycerate dehydrogenase, SerA, is a member of a D-isomer-specific family of 2-hydroxyacid dehydrogenases.

Oral Microbiol Immunol, 2000 Feb, 15(1), 10 - 4
Salivary mucin as related to oral Streptococcus mutans in elderly people; Baughan LW et al.; MG1 (MUC5b and MUC4) and MG2 (MUC7), predominant mucins in human whole saliva, provide lubrication and antimicrobial protection for oral tissues . This study examines potential relationships between Streptococcus mutans titers in the oral cavity and the following: mucin concentrations; unstimulated and stimulated whole saliva flow rates; decayed, missing, and filled tooth surfaces; and age of 24 elderly patients . S . mutans titers were determined using Denticult SM . Mucin concentrations were determined using Stains-all, sodium dodecyl sulfate-polyacrylamide gel electrophoresis . Logistic regression was used to identify potential relationships between the above variables . S . mutans classification served as the dependent variable . The remaining variables were possible predictor variables . The best model for predicting S . mutans category contained log MG2 as a predictor variable for all of its parameter estimates . No other set of parameter estimates were statistically significant . These results suggest that elevated S . mutans titers are significantly associated with diminished concentrations of MG2 in unstimulated whole saliva, as quantified in mucin-dye binding units.

J Appl Microbiol, 2001 Jan, 90(1), 53 - 8
A microcalorimetric comparison of the anti-Streptococcus mutans efficacy of plant extracts and antimicrobial agents in oral hygiene formulations; Morgan TD et al.; AIMS: This study aimed to evaluate the efficacy of 'natural' putative antimicrobial agents against Streptococcus mutans and to compare these with synthetic agents using the flow microcalorimeter . Streptococcus mutans is one of the oral pathogens responsible for dental caries . METHODS AND RESULTS: Traditional microbiological techniques are invasive and destructive unlike flow microcalorimetry . This rapid technique was used to continuously monitor the power output (bioactivity) of Strep . mutans with reproducibility, precision and accuracy . The antibacterial agents found in oral hygiene products and all the natural agents tested showed anti-Strep . mutans ability . CONCLUSION: In this study microcalorimetry identified agents that had a biological effect and quantified the rate of kill achieved enabling four broad categories of antimicrobial agent to be defined . SIGNIFICANCE AND IMPACT OF THE STUDY: Microcalorimetric data are a better indication of antimicrobial efficacy than merely determining concentrations at which an antimicrobial agent is bacteriostatic or bactericidal.

J Dermatol Sci, 2001 Jan, 25(1), 87 - 92
Normal proliferative responses of peripheral blood mononuclear cells to streptococcal preparation OK-432 in patients with pustulosis palmaris et plantaris constitute a distinct feature from the reduced responses observed in those with psoriasis vulgaris, pustular psoriasis, and acrodermatitis continua of Hallopeau; Takahashi K et al.; It was previously reported that peripheral blood mononuclear cells (PBMC) from the patients with psoriasis vulgaris (PV) showed a reduced proliferative response in vitro to the stimulation of a lyophilized preparation of penicillin-treated low virulence Su-strain of Streptococcus pyogenes group 3, OK-432 . In this study, at first it was examined whether OK-432 acts as a superantigen . By analyzing the usage of Vbeta T-cell receptor (TCR) of proliferating T cells stimulated with OK-432, it was found that OK-432 stimulated preferentially Vbeta2 TCR-bearing T cells . Next, to find differences in in vitro responses of PBMC among various types of sterile pustular dermatoses such as pustulosis palmaris et plantaris (PPP), acrodermatitis continua of Hallopeau (AC), and generalized pustular psoriasis (GPP), the proliferative responses of PBMC obtained from these patients under the stimulation of OK-432 were compared . When the PBMC was stimulated with interleukin (IL)-2, no significant difference was found in their proliferative responses among those obtained from the patients with these sterile pustular dermatoses, PV or healthy controls . However, like those from PV patients, PBMC from AC and GPP patients showed significantly smaller responses to OK-432 than those from the healthy controls . In contrast, the proliferative responses of PBMC from the patients with PPP to OK-432 was comparable to those from healthy controls . These results, in addition to its unique clinical and histopathological characteristics, suggest that PPP has a different pathogenetic background from that underlying PV, AC, or GPP.

Oral Microbiol Immunol, 2000 Oct, 15(5), 329 - 34
Genetic transformation in Streptococcus mutans requires a peptide secretion-like apparatus; Petersen FC et al.; Competence for genetic transformation in Streptococcus pneumoniae and Streptococcus gordonii involves the ComAB secretion apparatus, which is thought to export the competence-stimulating peptide . Homologous secretory systems are also used for the export of certain bacteriocins and bacteriocin-like peptides . In this study, a similar secretory apparatus was found in the Streptococcus mutans genome, and its role in transformation was investigated . Gene inactivation resulted in a mutant deficient in transformability . We suggest that secretion of a peptide, possibly the competence-stimulating peptide itself, is involved in competence induction also in S . mutans.

Oral Microbiol Immunol, 2000 Oct, 15(5), 325 - 8
Rate-limiting steps of glucose and sorbitol metabolism in Streptococcus mutans cells exposed to air; Iwami Y et al.; It has been supposed that rate of sorbitol metabolism in the air-exposed streptococcal cells could be limited by the low capacity to regenerate nicotinamide adenine dinucleotide (NAD) from reduced NAD (NADH) following inactivation of pyruvate formate-lyase by oxygen . The rate-limiting steps, however, have not been identified . The aim of this study was to examine the effect of temporary exposure of the streptococcal cells to air on the intracellular flux of glucose and sorbitol metabolism by measuring acid excretion, fluorescence dependent on cellular level of NADH, glycolytic intermediates and enzyme activities . The exposure of cells to air decreased the acid excretions during glucose and sorbitol metabolism . The analysis of the glycolytic intermediates and the fluorescence suggested that the reduced level of acid excretion in the air-exposed glucose metabolizing cells resulted from the decrease in pyruvate catabolism . In the presence of sorbitol, the decreased acid production resulted from the reduced rates of the reactions catalyzed by sorbitol-phosphoenolpyruvate phosphotransferase and sorbitol 6-phosphate dehydrogenase because of shortage of substrates for these enzymes in addition to the decrease in pyruvate catabolism.

Oral Microbiol Immunol, 2000 Oct, 15(5), 317 - 24
Suppression of urease levels in Streptococcus salivarius by cysteine, related compounds and by sulfide; Sissons CH et al.; Urease synthesis in Streptococcus salivarius is induced by an acid environment, carbohydrate and a high growth rate . We now report that both cysteine and sulfide above 1 mM strongly suppress S . salivarius urease levels . Close structural relatives of cysteine (cysteamine, ethanedithiol and penicillamine) at 5 mM buffered to pH 7.0 also caused urease suppression, but thiols in general (2-mercaptoethanol, dithiothreitol and glutathione) did not . In cultures buffered below pH 5.9, the cysteine-induced urease suppression was lifted substantially, but the sulfide suppression increased, suggesting involvement of different processes . Urease activity was inhibited 50% by 5 mM mercaptoethanol but unaffected by 5 mM cysteine or sulfide, hence modification of enzyme activity by thiols is not directly related to suppression of their levels in culture . Cysteine, arising primarily through protein hydrolysis which also raises the pH, could be a surrogate pH feedback signal for nearby alkaline conditions, and sulfide may reflect activity of periodontopathic plaques.

Oral Microbiol Immunol, 2000 Oct, 15(5), 313 - 6
In vitro evaluation of the retention of three species of pathogenic microorganisms by three different types of toothbrush; Bunetel L et al.; The retention and survival of microorganisms on toothbrushes pose a threat of recontamination for certain patients at risk . In order to measure the influence of brush design and optimize the choice of toothbrush model for complementary studies, the in vitro retention of three microbial species (Porphyromonas gingivalis ATCC 33277, Streptococcus mutans ATCC 25175 and Candida albicans ATCC 26555) was evaluated for three types of toothbrush . Two series of standardized experiments were carried out for each brush and microorganism . The first series tested the retention of the microorganisms on the head portion of the brush, while the second measured retention on the head of the brush and the part of the handle inserted in the mouth during brushing . For each series, the microorganisms were counted at T0 and T24 (after storage of the brushes at room temperature for 24 h) . Depending on the microorganism studied, from 0.2% to 2% of the initial inoculum was retained on the brush . The number detected increased with the size of the exposed area . After 24 h, P . gingivalis and S . mutans were found on only one type of brush . C . albicans survived on all three . These results confirm that microorganisms can quickly colonize toothbrushes.

Oral Microbiol Immunol, 2000 Aug, 15(4), 258 - 62
Simple and rapid detection of Streptococcus mutans and Streptococcus sobrinus in human saliva by polymerase chain reaction; Oho T et al.; Streptococcus mutans and Streptococcus sobrinus are major pathogens causing dental caries in humans . A simple and rapid method to detect these species in human saliva simultaneously was developed using the polymerase chain reaction (PCR) . Chromosomal DNA was extracted by boiling bacterial cells in lysis solution containing 1% Triton X-100 . Oligonucleotide primers specific for portions of the glucosyltransferase genes (gtfB of S . mutans and gtfI of S . sobrinus) were designed . After PCR using two sets of these primers, S . mutans and S . sobrinus were specifically identified . The method was capable of amplifying DNA fragments specific for these species from chromosomal DNA extracted from 1 x 10(3) cells, or from 10 microliters of clinical saliva samples containing 1 x 10(3) colony-forming units of either streptococcal species . A second PCR, using the first PCR product as a template with newly designed internal primers, made it possible to detect 1 x 10(2) colony-forming units of either streptococcal species in 10 microliters of saliva samples . These results indicate that the PCR method developed in this study is useful for detecting S . mutans and S . sobrinus in saliva and that it can be used in epidemiological studies to evaluate the prevalence level of these organisms.

Oral Microbiol Immunol, 2000 Aug, 15(4), 249 - 57
Xylitol disturbs protein synthesis, including the expression of HSP-70 and HSP-60, in Streptococcus mutans; Hrimech M et al.; Xylitol, a natural sugar alcohol and a caries-preventive carbohydrate sweetener, inhibits xylitol-sensitive wild-type Streptococcus mutans but also selects for its natural xylitol-resistant mutants . The aim of the work was to verify the influence of xylitol on heat shock proteins HSP-60 (GroEL-like) and HSP-70 (DnaK-like) in xylitol-sensitive and xylitol-resistant strains . Cells from fresh isolate S . mutans 123.1 were grown at 37 degrees C and constant pH 7.0 . The cell culture was stressed by raising the temperature to 43 degrees C or adding xylitol (4% final) . Cell proteins labeled with a cocktail of 14C-amino acids were analyzed by SDS-PAGE and autoradiography whereas HSP-60 and HSP-70 were visualized using Western immunoblotting . In both xylitol-sensitive and xylitol-resistant strains, heat stress was associated with an increase of both HSP-60 (63 kDa) and HSP-70 (71 kDa) and a decrease in the intensity of a number of other protein bands compared with cells maintained at 37 degrees C . Exposure to xylitol but not to other polyols induced a decrease of both these heat shock proteins in the xylitol-sensitive strain but did not modify them in the xylitol-resistant mutant . It also decreased all protein bands above 60 kDa together with a 53 kDa protein and increased the amount of 57-, 50- and 40-kDa proteins in the xylitol-sensitive strain whereas the proteins of the xylitol-resistant strain remained unchanged . The results suggest that xylitol is a strong metabolic inhibitor that disturbs protein synthesis and reduces the expression of HSP-70 and HSP-60 proteins in the wild-type xylitol-sensitive S . mutans but not in the xylitol-resistant natural mutant strain.

J Chemother, 2000 Dec, 12(6), 495 - 8
In vitro activity of clarithromycin against penicillin-susceptible and penicillin-resistant strains of Streptococcus pneumoniae in a pharmacodynamic simulation model; Fuentes F et al.; Clarithromycin has shown enhanced activity against Streptococcus pneumoniae, but increased resistance to macrolides has been observed in recent years . Our aim was to investigate its activity against strains of S . pneumoniae with variable susceptibility to this antibiotic and to penicillin . We determined killing curves using the Centriprep-10 pharmacodynamic simulation model, which permits using varying antibiotic concentrations to mimic a pharmacokinetic human profile in serum (corresponding to an oral dose of 500 mg) . Four strains of S . pneumoniae were tested . In susceptible strains, clarithromycin showed bactericidal activity (reductions of up to 2.97 log10 cfu/ml of the initial inoculum) . In resistant strains, clarithromycin showed a bacteriostatic effect (<1 log10 cfu/ml reduction) . Penicillin-susceptible strains showed higher reductions than penicillin-resistant strains . This effect is important owing to the high minimum inhibitory concentration (MIC) of one of the resistant strains (32 microg/ml) . More studies are needed to explain this bacteriostatic activity.

J Chemother, 2000 Dec, 12(6), 475 - 81
Bactericidal activity of moxifloxacin compared to grepafloxacin and clarithromycin against Streptococcus pneumoniae and Streptococcus pyogenes investigated using an in vitro pharmacodynamic model; Esposito S et al.; The aim of the present investigation was to study and compare the killing activity of two new fluoroquinolone compounds, moxifloxacin and grepafloxacin, and a new generation macrolide, clarithromycin, against three clinical isolates of Streptococcus pneumoniae (penicillin-susceptible, -intermediate and -resistant) and two Streptococcus pyogenes (erythromycin-susceptible and -resistant) strains by simulating their human pharmacokinetics in a pharmacodynamic model . Results were achieved by measuring the reduction in viable bacterial count during the 24-h experimental period . All three antimicrobials led to a continuous reduction in the bacterial counts of penicillin-susceptible S . pneumoniae and erythromycin-susceptible S . pyogenes strains, the maximal reduction observed after 8-10 hours being 5-6 logs for moxifloxacin and 3 logs for grepafloxacin; clarithromycin exhibited a similar reduction of 5 logs only after 24 h . No regrowth was observed for any strain after 24 h with any of the antibiotics . The bactericidal activity of both the fluoroquinolones was not affected by penicillin resistance of S . pneumoniae and erythromycin resistance of S . pyogenes . In contrast, clarithromycin was not able to reduce the bacterial count of penicillin-resistant S . pneumoniae and erythromycin-resistant S . pyogenes strains . Moxifloxacin exhibited, within 24 h, higher and faster bactericidal activity than grepafloxacin and clarithromycin against S . pneumoniae, and was not affected by penicillin resistance . These results suggest that moxifloxacin is a promising new agent for treatment of streptococcal infections.

Eur J Oral Sci, 2000 Dec, 108(6), 538 - 45
Xylitol-induced elevated expression of the gbpC gene in a population of Streptococcus mutans cells; Sato Y et al.; Xylitol possesses a unique property distinct from the other caries-preventive sweeteners . This sugar alcohol cannot be metabolized to acids but is taken up by Streptococcus mutans and accumulated as a toxic sugar-phosphate in the cells, resulting in growth inhibition . Due to the accumulation, xylitol induces biological responses including the emergence of xylitol-insensitive populations . Therefore, we expected another response induced by xylitol and found a new phenomenon, that cells repeatedly cultured in the presence of xylitol evolved into those exhibiting an elevated dextran-dependent aggregation phenotype . This phenotype was found to result from expression of the gbpC gene, which was previously reported to be expressed only under certain stress conditions . Construction of a Strep . mutans isogenic mutant carrying the gbpC::lacZ fusion gene indicated that gbpC expression of cells repeatedly cultured in the presence of xylitol was elevated 20-fold . DNA transfer experiments indicated that this phenotypic change did not appear to be due to a mutation . These cells also exhibited decreased adhesion to glass surfaces when grown in the presence of sucrose . This may be one of the ways by which some populations of Strep . mutans are removed from dental plaques.

Schweiz Med Wochenschr, 2000 Dec 9, 130(49), 1873 - 9
Pneumonia due to resistant Streptococcus pneumoniae; Tauber MG; In the past 10 to 20 years the pneumococcus, the most common pathogen of community-acquired pneumonia, has developed resistance to most antibiotics used for its treatment . Classes with important resistance problems include the beta-lactams, the macrolides and lincosamides, trimethoprim-sulfamethoxazole, and the tetracyclines . Unfortunately, resistance to more than one class of antibiotics is common in pneumococci, and their treatment is thus becoming more difficult . Patients likely to harbour resistant organisms include young children, particularly those attending day care, older patients, and subjects who have received recent antibiotic therapy, suffer from underlying diseases including HIV, or have nosocomial or polymicrobial pneumonia . The consequences of resistance development are different for different classes of antibiotics . With beta-lactams, the increase in minimal inhibitory concentrations is usually moderate in resistant strains, and because of the high concentrations that can be achieved with this class of drugs resistance does not usually lead to treatment failure . Thus, beta-lactams continue to be important drugs for the treatment of pneumococcal pneumonia, even if the organism is resistant . In contrast, resistance to other classes of antibiotics must be assumed to render these drugs ineffective . Newer quinolones represent valuable alternatives for the treatment of pneumococcal pneumonia, since their efficacy is not affected by resistance to other classes of antibiotics and they cover almost all pathogens of community-acquired pneumonia, including the atypical pathogens . However, they should be used with restraint in order to preserve this valuable class of drugs.

J Reprod Med, 2000 Dec, 45(12), 979 - 82
Antibiotic resistance patterns of group B streptococcus in antenatal genital cultures; Silverman NS et al.; OBJECTIVE: To identify the antibiotic susceptibility patterns of group B streptococcus (GBS) isolated from antenatal genital screening cultures . STUDY DESIGN: One hundred thirty-five sequential GBS isolates underwent susceptibility testing by Kirby-Bauer disk diffusion to a variety of commonly used antibiotics . RESULTS: All isolates were susceptible to cefazolin, chloramphenicol and vancomycin . Resistance to clindamycin and erythromycin, the currently recommended alternative antibiotics for intrapartum GBS prophylaxis in penicillin-allergic women, was found in 8.2% and 9.6% of GBS isolates tested, respectively . CONCLUSION: These findings raise concerns regarding the need for both confirmation of a history of penicillin allergy in pregnant women and performance of antibiotic susceptibility testing on GBS isolated in genital screening cultures from penicillin-allergic patients.

Radiology, 2001 Jan, 218(1), 211 - 4
Diagnostic yield of CT-guided percutaneous aspiration procedures in suspected spontaneous infectious diskitis; Chew FS et al.; PURPOSE: To evaluate the diagnostic yield of computed tomography (CT)-guided percutaneous needle aspiration procedures in the setting of suspected spontaneous infectious diskitis and to assess the usefulness of concurrent cytologic examination as a supplement to microbiologic evaluation . MATERIALS AND METHODS: A retrospective study was performed to evaluate 105 consecutive CT-guided percutaneous disk space aspiration procedures in 92 patients suspected of having spontaneous (non-postoperative) infectious diskitis . Our criterion standard for the presence of active infection was the identification of a pathogen either from the CT-guided aspiration specimen or from a surgical specimen . All cases had microbiologic analysis, 78 cases had cytopathologic analysis, and 31 cases had open surgery . RESULTS: Microbiologic analysis of the CT-guided percutaneous aspiration specimens was positive in 39 of 43 cases proved to have active infections, with four false-negative and no false-positive cases (sensitivity, 91%; specificity, 100%) . The false-negative cases were all active fungal infections identified from surgical specimens . Adding cytopathologic analysis to microbiologic analysis improved sensitivity but reduced specificity . The most common pathogens were species of Staphylococcus, Streptococcus, Candida, and Mycobacterium . All 30 active bacterial infections were identified with the CT-guided procedures, but only five of nine fungal infections were identified . CONCLUSION: CT-guided percutaneous needle aspiration is an accurate method for identifying active bacterial disk space infections but is less reliable for identifying fungal infections.

J Antimicrob Chemother, 2001 Jan, 47(1), 33 - 42
HMR 3647 human-like treatment of experimental pneumonia due to penicillin-resistant and erythromycin-resistant Streptococcus pneumoniae; Piroth L et al.; An experimental Streptococcus pneumoniae pneumonia model in rabbits was used to assess the efficacy of amoxycillin, erythromycin and a new ketolide, telithromycin (HMR 3647) . The MICs of amoxycillin, erythromycin and HMR 3647 for the three clinical S . pneumoniae strains used were, respectively, (mg/L): 0.01, 16 and 0.02 (strain 195); 2, 0.25 and 0.02 (strain 16089); 8, >64 and 0.02 (strain 11724) . Antibiotic therapy reproduced human serum pharmacokinetics (amoxycillin 1 g iv tds or erythromycin 500 mg qds or HMR 3647 800 mg bd) . Forty-eight hours of therapy with HMR 3647 and amoxycillin resulted in significant bacterial clearance in the lungs and spleen of rabbits infected by S . pneumoniae strain 195 and strain 16089 (at least 3 log(10) cfu/g decrease, P < 0.001) . Erythromycin was active against only the erythromycinsusceptible strain (3 log(10) cfu/g decrease at 48 h, P < 0.001) . None of the antibiotics showed significant efficacy with strain 11724 . All agents produced significant bacterial clearance when time above MBC was >33%, and microbiological failure when it was <25%, whereas MIC was not correlated with microbiological outcome with HMR 3647 . Our findings suggest that pharmacodynamic data integrating MBC may be predictive of microbiological success or failure with greater accuracy than with MIC . HMR 3647 produced significant bacterial clearance in both penicillin- and erythromycin-resistant pneumonia, but was less effective against the highly erythromycin-resistant S . pneumoniae strain.

Arch Soc Esp Oftalmol, 2000 Oct, 75(10), 659 - 63
{Study of infectious keratitis in corneal graft}; Sanchez Perez A et al.; PURPOSE: This retrospective study was conducted to identify the associated risk factors and microbiologic spectrum in infectious keratitis (IK) after penetrating keratoplasty (PK) . METHODS: Medical records of 246 PK (corneal grafts for a 17-year period, 1980-1997) were reviewed to identify IK . Criterion for inclusion was IK in PK and positive corneal culture or smear Gram stain . PK indications, interval PK-IK, risk associations microbiologic study, complications, and final corneal graft clarity were reviewed . RESULTS: The incidence reported was 4.8%, 12 cases of IK identified in 246 PK performed . The most common PK diagnosis was herpes simplex keratopathy . Potential risk factors have been categorized in :1- Local ocular (graft discompensation, therapeutic contact lens, suture-related), 2- Topical medication (corticosteroids and antibiotics) and 3- Systemic causes (diabetes mellitus) . Time interval between PK-IK was 27.1+/-25.7 months (25% occurred within 12 months PK and suture complications were the main cause; 75% later than 12 months and corneal oedema and therapeutic contact lens the main late causes) . Microbial spectrum: 66.6% cases were bacterial, Gram (+) organisms were predominantly involved (Streptococcus and Staphylococci) and the remaining cases were fungal (Candida) . There was one case of infectious crystalline keratopathy due to Streptococcus Mitis . The prevalence of complications like evisceration and failure clear graft were 75% . CONCLUSIONS: IK after PK is an uncommon (4.8%) but serious complication . It proves a major later form incidence, associated to graft discompensation and contact lens use . Gram (+) bacterial organism and fungi (Candida) were predominantly involved.

Hepatogastroenterology, 2000 Nov-Dec, 47(36), 1633 - 5
A new etiology of acute abdominal emergencies in cirrhotic patient: secondary pneumococcal peritonitis with jejunitis; Regimbeau JM et al.; We report the first case of secondary pneumococcal peritonitis associated with acute jejunitis in a 52-year-old homeless Child-Pugh C cirrhotic man without ascitis . The patient was admitted with clinical signs of peritonitis, and jaundice . Morphologic examination was unremarkable . A laparotomy revealed a diffuse peritonitis, and an acute jejunitis with prenecrotic lesion . The lesion was located within the first centimeters of the jejunum, immediately after the duodeno-jejunal angle, extented on 15 cm . A resection of the first 15 cm of the jejunum was performed with duodeno-jejunal side-to-side manual anastomosis . Gram-stain and cultures of blood, peritoneal pus, and jejunal mucosa revealed a penicillin-sensitive Streptococcus pneumoniae . Appropriate parenteral antibiotic treatment was initiated (aminopenicillin) . The postoperative course was marked by a transient hepatic failure associated with an ascitis controlled by diuretics . The patient was discharged on the 26th day after surgery . This case reports a new etiology of acute abdominal emergencies in cirrhotic patients.

J Am Acad Dermatol, 2001 Jan, 44(1), 17 - 21
Erythema nodosum in children: a prospective study; Kakourou T et al.; BACKGROUND: The studies of series of children with erythema nodosum (EN) are limited and mostly retrospective . OBJECTIVE: We evaluated the epidemiology, etiology, clinical manifestations, course, and prognosis of EN in children . METHODS: Thirty-five children with EN (17 boys, 18 girls; mean age, 8.79 years) have been studied . Four excluded children proved, on biopsy, to have leukocytoclastic vasculitis (n = 3) or eosinophilic cellulitis (n = 1) . RESULTS: In 27 of the 35 children (77%), the etiology of EN was established by laboratory investigations . In 25 children the causative factor of EN was an infectious agent (including beta-hemolytic streptococcus {n = 17}, and Mycobacterium tuberculosis {n = 2}), whereas in 2 patients, EN was associated with Crohn's disease in one and Hodgkin's disease in the other . In 8 of the 35 children (23%) the etiology of EN remained undetermined . The mean duration of the rash was 11.5 days . Recurrences were noted in only 2 children (1 episode in 1 child and 3 episodes in the other) . CONCLUSION: Currently the most common provoking agent of EN in children in Greece is beta-hemolytic streptococcus . However, Mycobacterium tuberculosis should still be considered as a cause of the disorder . Also, the course of EN is benign and recurrences are exceptional.

An Esp Pediatr, 2000 Dec, 53(6), 567 - 72
{Orbital and periorbital cellulitis . Review of 107 cases}; Rodriguez Ferran L et al.; AIM: To report the epidemiology, clinical features, management and complications of orbital and periorbital cellulitis; to evaluate the use of imaging tests in the detection of complications . METHODS: Retrospective study of 107 pediatric patients admitted to the San Joan de Deu Pediatric Hospital with orbital or periorbital cellulitis from January 1991 to January 1999 . RESULTS: The incidence of cellulitis was highest in the second year of life and during winter . No significant differences were found between the sexes . In 68 patients (63.6%) the cause of cellulitis was identified as sinusitis . The most frequently identified organisms were Staphylococcus aureus, Streptococcus pneumoniae and S . pyogenes . Computed tomography identified retroseptal damage in 36 patients with 23 super osteal abscesses, 3 orbital abscesses and 3 intracranial complications . Sixty nine percent of the patients were treated with a single antibiotic (cefotaxime, cefuroxime or amoxicillin clavulanic acid) while 31% underwent multiple antibiotic therapy . Only 8.4% required surgery . CONCLUSIONS: Orbital cellulitis is a relatively common and potentially serious disease in children . The early use of CT to assess the extent of damage is important in establishing prognosis and in assessing the need for surgical therapy.

J Laryngol Otol, 2000 Nov, 114(11), 832 - 6
Protective role of superoxide dismutase in rat eustachian tubal mucosa against acute otitis media induced by upper respiratory tract infection; Lee ES et al.; Superoxide dismutase has been known to play a role as an anti-oxidative system against oxidative injury during acute inflammation . To investigate the role of superoxide dismutase in eustachian tubal mucosa during acute otitis media (AOM), an animal model was made . Sprague-Dawley rats were inoculated with Streptococcus pneumoniae through the nasal cavity following development of virus-induced upper respiratory infection . The animals were divided into three groups according to their tympanic cavity conditions following bacterial inoculation; inoculated animals with no resultant AOM (no-AOM), animals with resultant AOM (AOM) and animals with resolving otitis media (recovery) . The changes of superoxide dismutase in each tubal mucosa were compared with that of the normal control using immunohistochemistry and immunoblotting methods . On Western blot, there were little changes of optical density and surface area in no-AOM (213.5 +/- 22.4, 13.2 +/- 0.8 mm2) and recovery group (219.3 +/- 18.7, 14.8 +/- 0.7 mm2) compared to the normal control (223.5 +/- 26.2, 16.7 +/- 0.4 mm2) . However, a marked decrease was found in the AOM model (167.6 +/- 19.3, 6.5 +/- 0.9 mm2) . These findings suggest that superoxide dismutase may play a role in protecting tubal mucosa from free radical injury during AOM.

Ann Pharmacother, 2000 Dec, 34(12), 1452 - 68
treatment and prevention of otitis media; Erramouspe J et al.; OBJECTIVE: To review and summarize recent advances in the treatment and prevention of otitis media (OM) . DATA SOURCES: A MEDLINE search (1996-March 2000) was performed to identify relevant primary and review articles . References from these articles were also reviewed if deemed important . STUDY SELECTION AND DATA EXTRACTION: English-language primary and review articles focusing on the treatment and prevention of acute otitis media (AOM) were included . Studies focusing exclusively on OM with effusion or serous OM and chronic suppurative OM were excluded . Information regarding prevention and drug therapy was reviewed, with an emphasis placed on advances made in the last two years . DATA SYNTHESIS: Recently, an expert panel of the Centers for Disease Control and Prevention recommended use of only three of 16 systemic antibiotics approved by the Food and Drug Administration for treatment of AOM: amoxicillin, cefuroxime axetil, and ceftriaxone . Controversy exists over the importance of key selection factors used by the expert panel in determining which antibiotics to recommend in a two-step treatment algorithm, that is, in vitro data, pharmacodynamic profiles, and necessity for coverage of drug-resistant Streptococcus pneumoniae at all steps of empiric treatment . Additional antibiotic and patient selection factors useful for individualizing therapy include clinical efficacy, adverse effects, frequency and duration of administration, taste, cost, comorbid infections, and ramifications should bacterial resistance develop to the chosen antibiotic . Presumed or past patient/caregiver adherence (especially when antibiotic failure has occurred) is also paramount in selecting antibiotic therapy . A three-step treatment algorithm for refractory AOM that employs amoxicillin, trimethoprim/sulfamethoxazole (TMP/SMX), or high-dose amoxicillin/clavulanate (depending on the prior dose of and adherence to amoxicillin therapy), and ceftriaxone or tympanocentesis at steps 1, 2, and 3, respectively, appears rational and cost-effective . The recent upsurge in antimicrobial resistance is highlighted, and recommendations are presented for the treatment of AOM and prevention of recurrent otitis media (rAOM) . CONCLUSIONS: Amoxicillin remains the antibiotic of choice for initial empiric treatment of AOM, although the traditional dosage should be increased in patients at risk for drug-resistant S . pneumoniae . In cases refractory to high-dose amoxicillin, TMP/SMX should be prescribed if adherence to prior therapy seemed good or complete, or high-dose amoxicillin/clavulanate if adherence was incomplete or questionable . Ceftriaxone should be reserved as third-line treatment . The increasing prevalence of drug-resistant S . pneumoniae emphasizes the importance of alternative medical approaches for the prevention of OM, as well as judicious antibiotic use in established cases . Removal of modifiable risk factors should be first-line therapy for prevention of rAOM . We support the use of conjugate pneumococcal vaccine per guidelines for prevention of rAOM from the Advisory Committee on Immunization Practice of the Centers for Disease Control and Prevention, with consideration given to influenza vaccine for cases of rAOM that historically worsen during the flu season . Sulfisoxazole prophylaxis should be reserved for children who are immunocompromised, have concurrent disease states exacerbated by AOM, or meet the criteria of rAOM despite conjugate pneumococcal and influenza vaccination . Therapy should be intermittent, beginning at the first sign of an upper respiratory infection, and should continue for 10 days . The invasive nature and risks of anesthesia relegate myringotomy, tympanostomy tubes, and adenoidectomy to last-line therapies for rAOM.

Pediatr Infect Dis J, 2000 Dec, 19(12 Suppl), S159 - 65
Comparative safety and efficacy of cefdinir vs amoxicillin/clavulanate for treatment of suppurative acute otitis media in children; Block SL et al.; OBJECTIVE: Two dosage regimens of cefdinir were compared with amoxicillin/clavulanate for the treatment of suppurative acute otitis media (AOM) in children . METHODS: This was an investigator-blinded, randomized, comparative, multicenter trial, in which tympanocentesis was performed in 384 patients, ages 6 months to 12 years, who had nonrefractory AOM . Patients were randomized to receive one of three 10-day treatment regimens: cefdinir 14 mg/kg daily (QD; n = 128); cefdinir 7 mg/kg twice a day (BID; n = 128); or amoxicillin/clavulanate 40/10 mg/kg/day divided for use three times a day (TID; n = 128) . RESULTS: Of the 384 enrolled patients 303 were evaluable for clinical efficacy . Clinical success rates were statistically equivalent for the 3 treatment groups at the end of therapy: 85 of 102 (83.3%) for cefdinir QD; 81 of 101 (80.2%) for cefdinir BID; 86 of 100 (86%) for amoxicillin/clavulanate . Of the 197 evaluable patients from whom a susceptible pathogen was recovered, presumptive eradication rates at end of therapy were equivalent: 55 of 65 (84.6%), 54 of 66 (81.8%) and 55 of 66 (83.3%) for cefdinir QD-, cefdinir BID- and amoxicillin/clavulanate-treated patients, respectively . However, presumptive eradication rates for Streptococcus pneumoniae were significantly lower for cefdinir BID (55.2%) than for amoxicillin/clavulanate (89.5%; P = 0.0019) and marginally lower than for cefdinir QD (80%; P = 0.054) . Diarrhea was the most common treatment-associated adverse reaction in all groups but was significantly more common in amoxicillin/clavulanate-treated patients (35%) than in patients who had been treated with cefdinir QD (10%, P<0.001) or cefdinir BID (13%, P<0.001) . CONCLUSIONS: A 10-day regimen of cefdinir 14 mg/kg QD or 7 mg/kg BID was as clinically effective overall as a 10-day regimen of amoxicillin/ clavulanate 40/10 mg/kg/day divided TID in the treatment of tympanocentesis-confirmed, nonrefractory AOM in children . These data suggest that cefdinir QD may be a better alternative than cefdinir BID for refractory AOM . Both dosing regimens of cefdinir were associated with significantly fewer gastrointestinal adverse reactions than was amoxicillin/clavulanate.

Pediatr Infect Dis J, 2000 Dec, 19(12), 1141 - 7
Impact of human immunodeficiency virus type 1 on the disease spectrum of Streptococcus pneumoniae in South African children; Madhi SA et al.; BACKGROUND: HIV-infected children are at increased risk of developing invasive Streptococcus pneumoniae disease . OBJECTIVE: To determine the impact of the HIV epidemic on the epidemiology of invasive pneumococcal disease in hospitalized African children . METHODS: Children <12 years of age with invasive pneumococcal disease were enrolled between March, 1997, and February, 1999 . RESULTS: The seroprevalence of HIV was 64.9% (146 of 225) . In children with pneumococcal isolates from serogroups 6, 9, 14, 19 or 23 (pediatric serogroups), pneumonia and pneumonia with concurrent meningitis was more common in HIV-infected children (P = 0.03 and P = 0.003, respectively), whereas septic shock occurred more often in HIV-uninfected children (P = 0.0003) . The overall burden of severe invasive pneumococcal disease was 41.7 (95% confidence interval, 26.5 to 65.6) fold increased in HIV-infected compared with HIV-uninfected children . Reduced susceptibility to penicillin (45.91% vs . 27.9%, P = 0.009), trimethoprim-sulfamethoxazole (44.5% vs . 19.0%, P = 0.0002) and multiple drug resistance was more common in HIV-infected than in HIV-uninfected children (24.0% vs . 6.4%, P = 0.01), respectively . The increased burden of disease and reduced antibiotic susceptibility of pneumococcal isolates in HIV-infected children was because of a heightened susceptibility to disease caused by pediatric serogroups in these children than in HIV-uninfected children (P = 0.01) . Although the case fatality rates did not differ between HIV-infected and -uninfected children, mortality in HIV-infected children with advanced AIDS (Stage C, 22 of 61; 36.1%) was greater than that in children with moderate AIDS (Stage B, 12 of 85; 14.1%, P = 0.002) . CONCLUSIONS: In children with invasive pneumococcal disease caused by the pediatric serogroups, HIV-infected children have more antibiotic-resistant isolates and have a different clinical presentation than do HIV-uninfected children.

Pol Merkuriusz Lek, 2000 Oct, 9(52), 684 - 6
{Occurrence and susceptibility to antibiotics of Streptococcus pyogenes strains from purulent infections in soft tissues}; Kania I et al.; Occurrence and susceptibility to antimicrobial agents of Streptococcus pyogenes strains isolated from purulent infections of soft tissue were examined . The specimen was from hospital and ambulatory patients in 1996-1998 . In general, 3665 samples were examined: 1841 wound swabs, 870 pus samples, 753 ulcer swabs and 101 from the decubitus ulcers . The ulcer of shank was the main diagnosis from which the Streptococcus pyogenes was isolated (38.8%) . The susceptibility to antimicrobial agents according to the disc-diffusion method was analyzed among the 59 S . pyogenes strains . 10.2% strains with the MLSB resistance were detected . All S . pyogenes strains were susceptible to penicillin, new quinolons and glicopeptides.

Medicine (Baltimore), 2000 Nov, 79(6), 360 - 8
Acute bacterial meningitis in adults . A 12-year review; Hussein AS et al.; One hundred three episodes of acute bacterial meningitis in adults hospitalized in Edmonton's 2 largest hospitals from 1985 to 1996 were reviewed . Cases complicating neurosurgery were excluded . Most cases were community-acquired (87%) . Twenty-three cases remained culture-negative, and there was no statistical relation between culture negativity and antibiotic pretreatment . Streptococcus pneumoniae was the predominant pathogen (52.5%), but Listeria monocytogenes was the second most common isolate, accounting for 12.5% of culture-positive cases . Compared to non-listerial meningitis, those with listeriosis were more likely to have negative cerebrospinal fluid (CSF) Gram stains (p = 0.07), CSF leukocyte counts < 1,000 cells/mm3 (p < 0.003), and normal CSF glucose (p = 0.006) . Bacterial antigen detection was found to be of low sensitivity: 33% in all patients, but only 9% in cases with negative CSF Gram stains . The overall mortality was 18%, with 15 deaths directly attributable to acute meningitis; the case-fatality rates for S . pneumoniae and L . monocytogenes were 24% and 40%, respectively . Mortality was significantly higher among those with seizures (34% versus 7%, respectively; p < 0.001; OR = 17.6) . Despite the urgency of acute bacterial meningitis, there were considerable delays in the institution of empiric antibiotics; mortality rates were slightly higher in those who experienced such a delay (16% versus 7% respectively; p = 0.18).

J Med Assoc Thai, 2000 Oct, 83(10), 1274 - 7
Streptococcus suis peritonitis: case report; Vilaichone RK et al.; A 45-year-old Thai man who presented with peritonitis was seen in a tertiary care centre in Thailand . An exploratory laparotomy was done because of peritonitis from abdominal trauma . Postoperatively the patient received intravenous ceftriaxone and metronidazole, but he developed rhabdomyolysis and acute renal failure . Hemodialysis was performed . After 8 days, the peritonitis had relapsed with hypotension . The patient was given vasopressives but clinicaly deteriorated and expired on day 11 . The peritoniteal fluid culture grew Streptococcus suis serotype 2 and the organism was resistant to multiple antimicrobial agents including penicillin (MIC > 32 mcg/ml) but was susceptible to vancomycin.

Salud Publica Mex, 1999 Sep-Oct, 41(5), 397 - 404
{Clinico-microbiological characteristics of meningitis caused by penicillin-resistant Streptococcus pneumoniae}}; Gomez-Barreto D et al.; OBJECTIVE: To evaluate the susceptibility to antibiotics of Streptococcus pneumoniae isolated from cerebrospinal fluid of children with meningitis . To describe and compare the clinical and microbiological characteristics, treatment and outcome among children infected with strains either susceptible or resistant to penicillin and cephalosporin . MATERIAL AND METHODS: A total of 38 children with pneumococcal meningitis were prospectively enrolled in the Institutional Surveillance Program for Pneumococcal Infections during 1994-1998 . Clinical and laboratory data were collected by chart review . RESULTS: Of the 38 children, 24 (63%) were less than 2 years of age, 11 (28.9%) had drug-resistant S . pneumoniae, 18.4% had intermediate resistance, 10.5% high level resistance and 2.6% also showed high level resistance to cefotaxime . The only associated factors (by Fisher's exact test) associated to resistance were: previous use of antibiotics (p = 0.2), underlying disease (p < 0.001) . Course of illness and clinical course were similar for children infected with penicillin or cefotaxime susceptible, vs . non-susceptible strains . CONCLUSIONS: Current levels of S . pneumoniae resistance to penicillin and cephalosporin are not associated to an increase in mortality in children with meningitis.

South Med J, 2000 Dec, 93(12), 1217 - 20
Group C streptococcal infection in a prosthetic joint; Kleshinski J et al.; We present possibly the first reported case of prosthetic joint infection due to group C Streptococcus in a 53-year-old man . The patient was treated with surgical debridement along with extended intravenous antibiotics and long-term oral penicillin therapy . He was able to retain the prosthesis and at 4-year follow-up had no symptoms or evidence of recurrent clinical infection.

Schweiz Med Wochenschr, 2000, Suppl 125, 38S - 40S
{Cervical necrotizing fasciitis:clinicopathological aspects}; Nuber R et al.; INTRODUCTION: Necrotising fasciitis is a potentially fatal fulminant infection of the subcutaneous tissues . METHODS: Our series comprised 15 patients with severe necrotising fasciitis during a 6-year period (1994-1999) at the surgical and ENT department of the Cantonal Hospital in Lucerne . RESULTS: In 4 cases, the necrotising infection occurred in the head and neck, beginning with a mastoiditis, pharyngitis, tongue swelling and infection of the upper eyelid . The bacteria cultures showed in 3 cases streptococcus of group A, in one case there was a mixed flora . All patients underwent a surgical intervention combined with antibiotics, intensive care was also necessary . All 4 patients with necrotising fasciitis in head and neck survived, 3 of the 11 surgical cases died because of multiorgan failure . DISCUSSION: The high mortality in necrotising fasciitis can only be influenced if diagnosed and treated very early . There often is a difference between the local infection sings and the patient's condition . The treatment includes a sudden surgical intervention combined with antibiotic therapy and intensive care.

Schweiz Med Wochenschr, 2000, Suppl 125, 23S - 26S
{Bezold's abscess with wide extension to the lateral skull base}; Blaser B et al.; The case of a 72-year-old woman suffering from chronic otitis media is presented . This insulin dependent diabetic patient was under steroid therapy for collagenosis and suffered from chronic polysinusitis . After two preceding drainages of the mastoid (antrotomy and mastoidectomy), the patient developed putrid mastoiditis followed by Bezold's abscess, an epidural abscess and thrombosis of the sigmoid sinus . Lateral petrosectomy and drainage of the neck were performed, but the patient again developed an abscess with extension to the lateral skull base, the foramen magnum and the upper cervical spine . After a further operation with extensive drainage and a three-month course of antibiotic treatment with ceftriaxon, the infection finally healed . A germ of the Streptococcus milleri group was identified.

Schweiz Med Wochenschr, 2000, Suppl 125, 20S - 22S
{Effect of antibiotics on the occurrence and course of acute mastoiditis}; Romer M et al.; Acute mastoiditis is the most common complication of acute otitis media . In the last years routine antibiotic treatment of acute otitis media was questioned and even abandoned in some countries . The goal of our study was to investigate the influence of antibiotic treatment on the occurrence and clinical outcome of acute mastoiditis and to analyse the bacteriological findings . In a retrospective chart review we identified all patients with the diagnosis of acute mastoiditis who had been referred to our tertiary-care centre between 1992 and 1999 . We identified 48 patients with 50 episodes . 23 patients (48%) had received antibiotic treatment before admission whereas 25 (52%) had not . The patients with antibiotic pretreatment were older (18 years) than patients without antibiotics (6 years) and their referral was delayed . The most common isolated single pathogen was Streptococcus pneumoniae . All pneumococci were sensitive to penicillin . Acute mastoiditis may be the first clinical sign of a middle ear infection, especially in very young children . Adequate antibiotic pretreatment can not always prevent the development of acute mastoiditis even in the absence of penicillin resistant pathogens.

J Enzyme Inhib, 2000, 15(6), 571 - 81
The kinetic mechanism of 5-enolpyruvylshikimate-3-phosphate synthase from a gram-positive pathogen Streptococcus pneumoniae; Du W et al.; The Streptococcus pneumoniae 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase is a potential novel antibacterial target . The enzyme catalyzes a reversible transfer of an enolpyruvyl group from phospho(enol)pyruvate (PEP) to shikimate 3-phosphate (S3P) to give EPSP with the release of inorganic phosphate (Pi) . Understanding the kinetic mechanism of this enzyme is crucial to the design of novel inhibitors of this enzyme that may have potential as antibacterial agents . Steady-state kinetic studies of product inhibition and inhibition by glyphosate (GLP) have demonstrated diverse inhibition patterns of the enzyme . In the forward reaction, GLP is a competitive inhibitor with respect to PEP, but an uncompetitive inhibitor relative to S3P . Product inhibition shows that EPSP is a competitive inhibitor versus both PEP and S3P, suggesting that the forward reaction follows a random sequential mechanism . In the reverse reaction, GLP is an uncompetitive inhibitor versus EPSP, but a noncompetitive inhibitor versus Pi . This indicates that a non-productive quaternary complex might be formed between the enzyme, EPSP, GLP and Pi . Product inhibition in the reverse reaction has also been investigated . The inhibition patterns of the S . pneumoniae EPSP synthase are not entirely consistent with those of EPSP synthases from other species, indicating that EPSP synthases from different organisms may adopt unique mechanisms to catalyze the same reactions.

J Clin Periodontol, 2000 Dec, 27(12), 875 - 82
Humoral immunity host factors in subjects with failing or successful titanium dental implants; Kronstrom M et al.; BACKGROUND: Treatment with titanium dental implants is in general successful . However, an unknown number of implants do not integrate and are removed either by exfoliation or at the time of second stage surgery . It would be of importance to identify subjects at risk and predict early implant failure . METHODS: In a retrospective study serum IgG antibody titers and avidity in sera from 40 subjects who had experienced titanium dental implant treatments with non-osseo-integration as the outcome (NOTI) and in sera from 40 age and gender matched control subjects who had received successful titanium dental implants (SOTI) were studied . Serum IgG titers to whole cell Actinomyces viscosus, Bacteroides forsythus, Porphyromonas gingivalis, Staphylococcus aureus, and Streptococcus intermedius sonicated antigen preparations were studied by ELISA . RESULTS: Serum IgG antibody titers to S . aureus were significantly higher in subjects with SOTI than in NOTI (p<0.001) suggesting that higher titers indicate protection against implant failure as a result of S . aureus infection . Statistically significant higher serum IgG antibody avidity to P . gingivalis and B . forsythus were found in subjects with SOTI than in subjects with NOTI (p<0.01 and p<0.001, respectively) . Statistical analysis failed to demonstrate antibody titer or avidity differences to the other pathogens studied . The likelihood that SOTI was associated with a high OD reading for S . aureus was 13.1:1 (p<0.001) . Whether subjects were edentulous or not, or if they had lost teeth because of periodontitis or caries did not seem to matter . CONCLUSION: Serum IgG antibodies relative to B . forsythus, P . gingivalis and S . aureus may be associated with the outcome of implant procedures and explain why early implant failures occur.

J Dermatol, 2000 Nov, 27(11), 750 - 2
A case of varicella complicated by cellulitis and scarlet fever due to Streptococcus pyogenes; Oyake S et al.; We report a 4-year-old boy with cellulitis and scarlet fever due to streptococcal infection following the onset of varicella . He developed a painful ulcer and subcutaneous induration on the left shoulder and a small, light-red-colored rash on the trunk at approximately the same time as the development of vesicles over the entire body . Streptococcus pyrogenes was isolated from samples from the posterior intranasal space and the ulcer on the shoulder . The clinical symptoms improved with the administration of antibiotics and intravenous drip infusion, but it took approximately one month from the first visit for the subcutaneous induration to disappear and the ulcer to heal with epithelialization . The complication of secondary streptococcal infection in varicella is relatively rare in Japan, but in Western countries there have been many reported cases of life-threatening necrotizing fasciitis and necrotizing pyomyositis due to secondary streptococcal infection following varicella . Close attention should be paid to streptococcal infection as a complication of varicella.

J Dermatol, 2000 Nov, 27(11), 706 - 10
The antibacterial activity of tea in vitro and in vivo (in patients with impetigo contagiosa); Sharquie KE et al.; A total number of 104 patients with impetigo contagiosa was included in this study . They were 47 females (45.2%) and 57 males (54.8%) . Their ages ranged from one month to 40 years with a median of 4 years . This study was divided into two parts: PART I (in vitro): Thirty-five patients were swabbed to determine the microbiology of impetigo contagiosa which included 33 isolates of pure S . aureus (94.3%) and 2 of a combination of S . aureus and Streptococcus pyogenes (5.7%) . The antibacterial effect of tea liquor (lotion) against S . aureus proved very effective . Antibiotic sensitivity was done for all bacterial isolates of S . aureus . PART II (in vivo): The antibacterial effects of tea liquor and ointment were tested by treating 64 patients with impetigo contagiosa . Tea ointment was very effective with a cure rate of 81.3% . Forty patients were taken as controls and divided into two groups . The first one was given an ointment containing Framycetin and gramicidin (soframycin) with a cure rate of 72.2%; the other group was given oral cephalexin with a cure rate of 78.6% . To the best of our knowledge, this study was the first one which demonstrated the anti-bacterial action of crude tea in vivo, against impetigo contagiosa . Clinical data about impetigo are also included in this study.

Int J Antimicrob Agents, 2001 Jan, 17(1), 71 - 4
Antibacterial effect of the culture fluid of Lentinus edodes mycelium grown in submerged liquid culture; Hatvani N; The antimicrobial activity of the culture fluid of Lentinus edodes mycelium grown in submerged liquid culture was tested against some common bacterial species and Candida albicans . The mycelium-free culture fluid was bacteriostatic against Streptococcus pyogenes, Staphylococcus aureus and Bacillus megaterium . The substance responsible for the activity was heat-stable, could be extracted with chloroform and had a molecular weight under 10000 . These characteristics suggested that the component might be lenthionine, an antibacterial and antifungal sulphur-containing compound . The culture fluid was less toxic to human tissue culture cells than to microbes . The antibacterial activity and toxicity could not be attributed to the same component.

Int J Antimicrob Agents, 2001 Jan, 17(1), 33 - 7
Measurement of the bactericidal activity of fluoroquinolones against Streptococcus pneumoniae using the bactericidal index method; Morrissey I et al.; Kill curve analysis alone showed trovafloxacin to be more bactericidal than levofloxacin, grepafloxacin and moxifloxacin against four isolates of Streptococcus pneumoniae . However, using the bactericidal index (BI) method, levofloxacin was the most bactericidal fluoroquinolone using serum or lung biopsy concentration levels against the ofloxacin-susceptible strains and trovafloxacin was the most bactericidal against the ofloxacin-intermediate strain . None of the fluoroquinolones was bactericidal against the ofloxacin-resistant strain . With BIs using epithelial lining fluid or alveolar macrophage concentration levels, trovafloxacin or grepafloxacin was most bactericidal, respectively . These data illustrate that simple analysis of traditional kill curves may not be adequate in the evaluation of fluoroquinolone bactericidal activity . The results of this study suggest a need for further investigation to assess the role of tissue concentration and bactericidal activity in antimicrobial efficacy.

J Neuroimmunol, 2001 Feb 1, 113(1), 30 - 9
Organotypic hippocampal cultures . A model of brain tissue damage in Streptococcus pneumoniae meningitis; Schmidt H et al.; Hippocampal slices of newborn rats were exposed to either heat-inactivated Streptococcus pneumoniae R6 (hiR6) equivalent to 10(6) and 10(8) CFU/ml, lipoteichoic acid (LTA) (0.3 microg/ml and 30 microg/ml), peptidoglycans (PG) (0.3, 30, 50 and 100 microg/ml), pneumococcal DNA (pDNA) (0.3 and 30 microg/ml) or medium only (control) . Cell injury was examined by Nissl staining, Annexin V and NeuN immunohistochemistry, and quantified by propidium iodide (PI) uptake and by determining neuron-specific enolase (NSE) concentration in the culture medium . Necrotic and apoptotic cell damage occurred in all treatment groups . Overall damage (Nissl and PI staining) was most prominent after hiR6 (10(8) CFU/ml), followed by LTA (30 microg/ml), pDNA (30 microg/ml), and not detectable after PG (30 microg/ml) exposure . PG (100 microg/ml) induced severe damage . Apoptotic cells were most frequent after exposure to LTA and hiR6 . Damage in the neuronal cell layers (NeuN, NSE) was most severe after treatment with hiR6 (10(8) CFU/ml), followed by PG (100 microg/ml), pDNA (30 microg/ml), and LTA (30 microg/ml).

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