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J Biol Chem, 2000 Mar 17, 275(11), 7497 - 504
Characterization of the linkage between the type III capsular polysaccharide and the bacterial cell wall of group B Streptococcus; Deng L et al.; The capsular polysaccharide of group B Streptococcus is a key virulence factor and an important target for protective immune responses . Until now, the nature of the attachment between the capsular polysaccharide and the bacterial cell has been poorly defined . We isolated insoluble cell wall fragments from lysates of type III group B Streptococcus and showed that the complexes contained both capsular polysaccharide and group B carbohydrate covalently bound to peptidoglycan . Treatment with the endo-N-acetylmuramidase mutanolysin released soluble complexes of capsular polysaccharide linked to group B carbohydrate by peptidoglycan fragments . Capsular polysaccharide could be enzymatically cleaved from group B carbohydrate by treatment of the soluble complexes with beta-N-acetylglucosaminidase, which catalyzes hydrolysis of the beta-D-GlcNAc(1-->4)beta-D-MurNAc subunit produced by mutanolysin digestion of peptidoglycan . Evidence from gas chromatography/mass spectrometry and (31)P NMR analysis of the separated polysaccharides supports a model of the group B Streptococcus cell surface in which the group B carbohydrate and the capsular polysaccharide are independently linked to the glycan backbone of cell wall peptidoglycan; group B carbohydrate is linked to N-acetylmuramic acid, and capsular polysaccharide is linked via a phosphodiester bond and an oligosaccharide linker to N-acetylglucosamine.

Vet Pathol, 2000 Mar, 37(2), 143 - 52
Pathogenesis of porcine reproductive and respiratory syndrome virus-induced increase in susceptibility to Streptococcus suis infection; Thanawongnuwech R et al.; Eighty 3-week-old crossbred pigs were randomly assigned to six groups (13-14 pigs/group) . Group 1 pigs served as uninoculated controls, group 2 pigs were inoculated intranasally (i.n.) with Streptococcus suis serotype 2, group 3 pigs were inoculated i.n . with a modified live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine, group 4 pigs were inoculated i.n . with the same vaccine and with S . suis, group 5 pigs were inoculated i.n . with VR-2385 (a high-virulence strain of PRRSV), and group 6 pigs were inoculated i.n . with VR-2385 and S . suis . Pigs exposed to both PRRSV and S . suis were inoculated with PRRSV 7 days prior to S . suis inoculation . The pigs were 26 days old when inoculated with S . suis . Respiratory disease was significantly more severe in groups 5 and 6 . Mortality rate was the highest in group 6 (87.5%) . This rate was significantly higher than that observed in all other groups except group 4 (37.5%) . The mortality rate in group 2, inoculated with S . suis alone, was 14.3% . No pigs from groups 1, 3, or 5 died prior to the scheduled necropsies at 10 and 28 days postinoculation with PRRSV (DPI) . To study the effect of PRRSV and/or S . suis on pulmonary clearance by pulmonary intravascular macrophages, six pigs from each group were intravenously infused with 3% copper phthalocyanine tetrasulfonic acid in saline prior to necropsy at 10 DPI . Mean copper levels in the lungs of pigs in groups 2, 5, and 6 were significantly lower than those in control pigs . The mean percentage of lung tissue grossly affected by pneumonia at 10 DPI was 0%, 1%, 0%, 3%, 64%, and 62% for groups 1-6, respectively . Both gross and microscopic interstitial pneumonia lesions were significantly more severe in the VR2385-inoculated groups (5 and 6) . PRRSV was isolated from bronchoalveolar lavage fluid collected at necropsy from 100% of the pigs in groups 5 and 6, 71.4% of pigs in group 4, 38.5% of pigs in group 3, and none of the pigs in groups 1 or 2 . Streptococcus suis serotype 2 was cultured from the internal tissues of 7.7%, 28.6%, and 78.6% of the pigs in groups 2, 4, and 6, respectively . Streptococcus suis serotype 2 was isolated from whole blood at necropsy from 7.7%, 35.7%, and 78.6% of pigs in groups 2, 4, and 6, respectively . Significantly more pigs in group 6 had S . suis isolated from whole blood and internal tissues . In summary, both high-virulence PRRSV and S . suis decreased copper clearance, and the incidence of isolation of S . suis and PRRSV was higher in dually inoculated pigs . PRRSV-induced suppression of pulmonary intravascular macrophage function may in part explain PRRSV-associated increased susceptibility to S . suis infection.

Mol Microbiol, 2000 Mar, 35(5), 1089 - 98
Regulation of competence for genetic transformation in Streptococcus pneumoniae: expression of dpnA, a late competence gene encoding a DNA methyltransferase of the DpnII restriction system; Lacks SA et al.; The chromosomal DpnII gene cassette of Streptococcus pneumoniae encodes two methyltransferases and an endonuclease . One methyltransferase acts on double-stranded and the other on single-stranded DNA . Two mRNAs are transcribed from the cassette . One, a SigA promoter transcript, includes all three genes; the other includes a truncated form of the second methyltransferase gene (dpnA) and the endonuclease gene . The truncated dpnA, which is translated from the second start codon in the full gene, was shown to produce active enzyme . A promoter reporter plasmid for S . pneumoniae was devised to characterize the promoter for the second mRNA . This transcript was found to depend on a promoter that responded to the induction of competence for genetic transformation . The promoter contains the combox sequence recognized by a SigH-containing RNA polymerase . As part of the competence regulon, the dpnA gene makes a product able to methylate incoming plasmid strands to protect them from the endonuclease and allow plasmid establishment . Its function differs from most genes in the regulon, which are involved in DNA uptake . Comparison of R6 and Rx strains of S . pneumoniae showed the temperature dependence of transformation in R6 to result from temperature sensitivity of the uptake apparatus and not the development of competence.

Am J Respir Crit Care Med, 2000 Mar, 161(3 Pt 1), 753 - 62
Treatment of gram-positive nosocomial pneumonia . Prospective randomized comparison of quinupristin/dalfopristin versus vancomycin . Nosocomial Pneumonia Group; Fagon J et al.; Nosocomial pneumonia is a frequent complication in hospitalized patients . Gram-positive pathogens, particularly Staphylococcus aureus, are responsible for the increasing frequency of nosocomial pneumonia . To evaluate the efficacy and safety of intravenous quinupristin/dalfopristin (Synercid) in the treatment of nosocomial pneumonia caused by gram-positive pathogens we conducted a prospective, randomized, open-label, international, multicenter, comparative clinical trial . Two hundred ninety-eight patients with nosocomial pneumonia were enrolled in 74 active centers in five countries: a subgroup of 171 (87 quinupristin/dalfopristin-treated and 84 vancomycin-treated patients) were evaluable for the major efficacy end points . One hundred fifty received 7.5 mg/kg of quinupristin/dalfopristin every 8 h; 148 patients received 1 g of vancomycin every 12 h . Aztreonam at a dose of 2 g every 8 h could be administered in both groups for coverage of gram-negative organisms, and tobramycin was added for coverage against Pseudomonas aeruginosa . The primary efficacy end point was the clinical response between the seventh and the thirteenth day after the end of treatment in clinically evaluable patients with documented causative pathogen(s) at baseline (bacteriologically evaluable population) . Therapy was clinically successful (cure or improvement) in 49 (56.3%) of patients receiving quinupristin/dalfopristin and 49 (58.3%) patients receiving vancomycin (difference, -2.0% {95% CI, -16.8% to 12.8%}) in the bacteriologically evaluable population . Equivalent clinical success rates were also observed in the all-treated population (n = 298), and in the bacteriologically evaluable patients intubated in baseline (39/72 {54%} compared with 36/67 {54%}) . The by-pathogen bacteriologic response was similar in both treatment groups, with equivalent clinical success rates for Streptococcus pneumoniae, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus . Adverse events (venous and nonvenous) were equally distributed between groups; 15.3% of quinupristin/dalfopristin patients and 9.5% of vancomycin patients discontinued therapy because of an adverse clinical event . In this study quinupristin/dalfopristin was shown to be equivalent to vancomycin in the treatment of nosocomial pneumonia caused by gram-positive pathogens . Quinupristin/dalfopristin merits further evaluation for the treatment of nosocomial pneumonia caused by methicillin-resistant S . aureus.

Anim Reprod Sci, 2000 Mar 15, 58(3-4), 241 - 51
Endocrine profiles of dairy cows following experimentally induced clinical mastitis during early lactation; Hockett ME et al.; Concentrations of LH, cortisol, estradiol-17beta (E(2)), prolactin and 13,14-dihydro-15-keto-prostaglandin F(2alpha) (PGFM) were determined in cows with experimentally induced clinical mastitis during early lactation . Cows free of intramammary infection (IMI) and in the luteal phase of the estrous cycle were balanced by lactation number and days in milk and assigned to either control (n=5) or treatment (n=5) groups . Treated cows were infected experimentally (day 0), in two mammary quarters, with Streptococcus uberis and developed clinical mastitis within 60 h after inoculation as evidenced by increased mastitis scores, elevated rectal temperatures, mammary swelling and isolation of S . uberis pathogen . Four days following bacterial challenge, blood samples were collected every 20 min for 8 h for determination of PGFM and LH following administration of oxytocin and GnRH, respectively . Blood samples were also collected on days 0, 4 and 7 of the experiment to determine concentrations of E(2), prolactin and cortisol . Four days after bacterial challenge, concentrations of cortisol were higher (P=0.04) in experimentally infected cows than controls . Experimentally challenged cows had increased (P=0.02) concentrations of cortisol on days 4 and 7 compared with day 0 . Control cows had no significant increase in blood cortisol during the experimental period . Baseline concentrations of PGFM did not differ between groups; however, peak concentrations of PGFM following oxytocin challenge were elevated (P=0.006) in cows with clinical mastitis compared with control animals . Prolactin, E(2) and LH did not differ between cows with clinical mastitis or controls . Experimentally induced mastitis during early lactation elevated concentrations of cortisol during the luteal phase of the estrous cycle . Furthermore, mastitic cows demonstrated an increased PGFM response following oxytocin administration . Altered reproductive efficiency in cows with clinical mastitis caused by Gram-positive pathogens may be the result of increased uterine sensitivity to prostaglandin F(2alpha) (PGF(2alpha)).

Crit Care Med, 2000 Feb, 28(2), 377 - 82
Nosocomial endocarditis in the intensive care unit: an analysis of 22 cases; Gouello JP et al.; OBJECTIVES: To review the intensive care unit experience of patients with admitted or acquired nosocomial endocarditis (NE) defined according to the Duke criteria . DESIGN: Prospective, cohort study . SETTING: University teaching hospital . PATIENTS: We reviewed the records of 22 patients documented with NE during a 6-yr period from 1992 to 1997 . INTERVENTIONS: None . MEASUREMENTS AND MAIN RESULTS: Twenty-two patients (9 women/13 men) aged 38-83 yrs (mean 65+/-9 yrs) had a NE (prevalence of 5 per 1,000 admissions) . For six patients, NE was the reason for the admission to the intensive care unit . For 17 patients, the time elapsed between admission and diagnosis of NE was 39+/-25 days . Sixteen patients were predisposed to infection and seven had underlying heart conditions that put them at risk for acute endocarditis: three prosthetic valves, two valvular diseases, and two cardiac pacemakers . In 21 cases (one unknown portal of entry), NE was the consequence of bacteremia related to a medical or surgical procedure: 11 intravascular devices, eight surgical wounds, one tracheal procedure, and one leg ulceration . The bacteriologic agents detected in blood cultures were: staphylococci (n = 17), Streptococcus (n = 2), Pseudomonas aeruginosa (n = 2), and Candida (n = 2) . Fourteen patients underwent echocardiography according to cardiac signs (cardiac failure, new cardiac murmur, or embolic event) . For the eight remainders, echocardiography was performed systematically because of fever and positive blood cultures . The lesions detected by 21 transthoracic and 17 transesophageal echocardiographs were the following: vegetations (n = 19), myocardial abscesses (n = 5), and valvular perforation (n = 1) . On 16 surgical indications, only five patients underwent surgery because the others were in too poor of a condition . The overall mortality was 68% (n = 15) and was directly associated with NE in 36% of cases (n = 8) . Seven patients (28%) were discharged 34 days after the diagnosis of endocarditis . CONCLUSIONS: NE is a frequent nosocomial infection that occurs late during hospitalization . Persistent fever with positive blood cultures is sufficient symptomology to promptly perform an echocardiogram . The poor prognosis is related to the poor condition of those patients who cannot be referred for surgical treatment.

J Med Microbiol, 2000 Mar, 49(3), 245 - 52
Epithelial cell response to challenge of bacterial lipoteichoic acids and lipopolysaccharides in vitro; Pollanen MT et al.; Accumulating dental plaque at the gingival margin contains lipoteichoic acids (LTAs) from the cell walls of gram-positive bacteria . In subgingival plaque associated with periodontal disease the amount of lipopolysaccharides (LPSs) from gram-negative bacteria increases . As the gingival junctional epithelium (JE) is an important structural and functional tissue, participating in the first line defence against apical advancement of dental plaque, this study examined the direct effects of LTAs (from Streptococcus mutans and S . sanguis) and LPSs (from Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola and Escherichia coli) on two epithelial cell lines (HaCaT and ERM) and a culture model for human JE . The cells were exposed to the LTAs or LPSs (10-50 microg/ml) for variable periods of time . None of the bacterial surface components had any effect on primary adhesion or on the epithelial attachment of the JE cultures . However, cell growth and mitotic activity were consistently reduced in all cultures treated with LTAs . In contrast, LPSs showed only slight or no effects on cell growth and mitotic activity depending on the epithelial cells used . This suggests that LPSs, despite their established role as modulators of inflammation, do not have direct harmful effects - at the concentrations found in dental plaque and gingival crevicular fluid - which would explain the mechanism of epithelial degeneration and detachment from the tooth surface . However, the LTAs appear to inhibit the renewal of epithelium and may thus contribute to degeneration of coronal JE and subgingival colonisation by periodontal pathogens.

N Engl J Med, 2000 Mar 9, 342(10), 681 - 9
Cigarette smoking and invasive pneumococcal disease . Active Bacterial Core Surveillance Team; Nuorti JP et al.; BACKGROUND: Approximately half of otherwise healthy adults with invasive pneumococcal disease are cigarette smokers . We conducted a population-based case-control study to assess the importance of cigarette smoking and other factors as risk factors for pneumococcal infections . METHODS: We identified immunocompetent patients who were 18 to 64 years old and who had invasive pneumococcal disease (as defined by the isolation of Streptococcus pneumoniae from a normally sterile site) by active surveillance of laboratories in metropolitan Atlanta, Baltimore, and Toronto . Telephone interviews were conducted with 228 patients and 301 control subjects who were reached by random-digit dialing . RESULTS: Fifty-eight percent of the patients and 24 percent of the control subjects were current smokers . Invasive pneumococcal disease was associated with cigarette smoking (odds ratio, 4.1; 95 percent confidence interval, 2.4 to 7.3) and with passive smoking among nonsmokers (odds ratio, 2.5; 95 percent confidence interval, 1.2 to 5.1) after adjustment by logistic-regression analysis for age, study site, and independent risk factors such as male sex, black race, chronic illness, low level of education, and living with young children who were in day care . There were dose-response relations for the current number of cigarettes smoked per day, pack-years of smoking, and time since quitting . The adjusted population attributable risk was 51 percent for cigarette smoking, 17 percent for passive smoking, and 14 percent for chronic illness . CONCLUSIONS: Cigarette smoking is the strongest independent risk factor for invasive pneumococcal disease among immunocompetent, nonelderly adults . Because of the high prevalence of smoking and the large population attributable risk, programs to reduce both smoking and exposure to environmental tobacco smoke have the potential to reduce the incidence of pneumococcal disease.

Vet Rec, 2000 Feb 5, 146(6), 159 - 61
Detection of DNA restriction fragment polymorphisms in Streptococcus equi; Takai S et al.; Large-restriction-fragment (LRF) polymorphisms in Streptococcus equi (S equi subspecies equi) were studied by pulsed-field gel electrophoresis . Five or six chromosomal fragments of between 194 and 915 kb were separated by digestion with the restriction endonuclease Notl . All 20 isolates of S equi, including 12 from independent Japanese outbreaks, four from independent American outbreaks, two from a single Irish outbreak, us vaccine strain F43, and type strain NCTC 9682 were successfully typed . Seven distinctive, reproducible and stable types were identified . The 12 Japanese isolates collected between 1992 and 1998 were of LRF type II suggesting that they were derived from the same source . The remaining eight isolates were of six types . The results indicate that LRF typing should be a useful technique for investigating the source and transmission of S equi.

J Community Health, 2000 Feb, 25(1), 23 - 33
Predicting cost-benefits before programs are started: looking at conjugate vaccine for invasive pneumococcal infections; Hueston WJ et al.; This analysis uses existing data to examine how an analysis to predict the net financial impact for an emerging medical program, namely a conjugate vaccine against Streptococcus pneumoniae, and to identify which key variables will have the greatest impact on the program's costs and benefits . Using data available on the prevalence and case fatality rates for invasive diseases caused by S pneumoniae, we examined the theoretical economic impact of vaccinating all newborns versus not vaccinating . Effectiveness estimates for conjugated pneumococcal vaccines and disease incidence and fatality rates were obtained from published sources . Because of scanty or inconclusive data for otitis media and pneumonia, the analysis was limited to cases of meningitis and bacteremia due to S pneumoniae . Based on these two diseases alone, immunization with conjugate pneumococcal vaccine could save an estimated 222 lives per million children vaccinated per year . Analysis of direct costs (projected immunization costs minus savings from reduced illness) show that a pneumococcal vaccine program will result in net direct costs between $0.08 and $2.42 per child . When indirect costs are included in the analysis, the vaccine is cost savings for all cases except when the two year incidence of disease and death rates are lowest and the cost of the vaccine series is $150 . Further research should focus on these key issues as the vaccine is introduced into use, as expected in the next few years.

Zentralbl Bakteriol, 2000 Jan, 289(8), 835 - 43
Complementary characterization of a hyaluronic acid splitting enzyme from Streptococcus agalactiae; Rodig H et al.; A hyaluronic acid splitting enzyme of Streptococcus agalactiae was characterized by splitting mechanism, Michaelis-constant and inhibition type for sulfated hyaluronic acid: The enzyme splits hyaluronic acid as a hyaluronate lyase {EC 4.2.2.1} . The Km = 8 x 10(-4) mg ml-1 was determined with the influence of substrate inhibition constant Kiu = 2 x 10(-6) mg ml-1 . Sulfated hyaluronic acid inhibits the enzyme in a partially non-competitive way . The inhibition constant is Ki = 5.47 x 10(-4) mg ml-1 . The GBS-hyaluronate lyase cleaves hyaluronic acid as an endoglycosidase . The work is related with the intention to establish a hyaluronate lyase of microbial origin as a therapeutical enzyme replacing bovine hyaluronidase.

Diagn Microbiol Infect Dis, 2000 Feb, 36(2), 81 - 4
Streptococcus pneumoniae from ophthalmic infections: serotype distribution and penicillin susceptibility; Mathews MS et al.; Streptococcus pneumoniae is one of the pathogens causing infection of the conjunctiva and the uveal tract . The present study began with the observation of two ophthalmic S . pneumoniae isolates showing intermediate resistance to penicillin . Among the 25 isolates of S . pneumoniae from 617 ophthalmic specimens, during the period of 14 months, four were found to exhibit an intermediate resistance to penicillin . Minimum Inhibitory Concentration values ranging from 0.125 microg/mL to 0.25 microg/mL was observed . No multidrug resistant strains were isolated . Serogrouping/typing of the S . pneumoniae revealed the following serogroups/types; 6A (n = 3), 6B (n = 2), 22 (n = 3), 14 (n = 3), 23A (n = 2), and 1 each of 23B, 19A, 7B, 32, 9, 42, 21, 39, 10, 3, and 34 . One strain showed cross reaction in pool 29, 35, and 47 . These findings represent the first such observation of ophthalmic isolates from India.

Mol Gen Mikrobiol Virusol, 2000, (1), 23 - 7
{New rare cutting restriction endonuclease SmII from Streptococcus milleri recognises 5'-ATTTAAAT-3'}; Dedkov VS et al.; New restriction endonuclease (restrictase) Smil of type II was detected in the bacterial strain Streptococcus milleri . Cellular lysate enzyme cut T7 and adenovirus-2 DNAs at site 5'-ATTT decreases AAAT-3' but not lambda DNA which does not contain this sequence . Intense aeration inhibited the growth of S . milleri . The content of restrictase in the cells was the greatest during the logarithmic growth phase . A total of 20,000 units of Smil were isolated from 4 g of cells by cellular extract fractionation with ammonium sulfate and subsequent chromatography on columns with Bio Gel A 0.5 m, heparin agarose, and phosphocellulose . Purified enzyme cut the synthetic oligonucleotide duplex in the center of the recognized site 5'-ATTT decreases AAAT-3' . Smil restrictase is a true isoschisomer of rare-cutting Swal enzyme . Smil belongs to a small group of enzymes which recognize octanucleotide sites and can be used for large-block fragmentation of DNA . Comparison of specificities of rare-cutting and other restrictases suggests that the enzymes recognizing octanucleotides can evolutionally originate from enzymes recognizing both hexanucleotides and tetranucleotides.

J Antimicrob Chemother, 2000 Mar, 45(3), 379 - 82
Therapeutic efficacy of J-111,225, a novel trans-3,5-disubstituted pyrrolidinylthio-1beta-methylcarbapenem, against experimental murine systemic infections; Shibata K et al.; In a murine model of systemic infection with methicillin-resistant Staphylococcus aureus (MRSA), J-111,225 showed an ED(50) value of 5 . 83 mg/kg, which was comparable to vancomycin (ED(50) 4.84 mg/kg), whereas imipenem failed to cure infected mice (ED(50) >100 mg/kg) . Against a mixed infection caused by MRSA and Pseudomonas aeruginosa, monotherapy with J-111,225 showed an ED(50) value of 7.23 mg/kg, whereas combined treatment with vancomycin plus imipenem (1:1) had an ED(50) of 20.86 mg/kg . J-111,225 showed good therapeutic efficacy against methicillin-susceptible S . aureus, penicillin-resistant Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae and P . aeruginosa . The unusually broad spectrum suggests that monotherapy with this novel carbapenem may be suitable for polymicrobial infections associated with MRSA.

J Antimicrob Chemother, 2000 Mar, 45(3), 315 - 20
Evaluation of combined ceftriaxone and dexamethasone therapy in experimental cephalosporin-resistant pneumococcal meningitis; Cabellos C et al.; The treatment of meningitis caused by strains of Streptococcus pneumoniae with decreased susceptibility to third-generation cephalosporins is an increasingly frequent and difficult problem . In this study a rabbit model of meningitis was used to determine the efficacy of ceftriaxone at different dosages, and to establish the effect of the addition of dexamethasone to the chemotherapeutic regimen . Groups of eight rabbits were inoculated with 10(6) cfu/mL of a cephalosporin- resistant strain of S . pneumoniae (MIC of cefotaxime/ceftriaxone 2 mg/L) . Eighteen hours after inoculation, ceftriaxone (50 or 100 mg/kg/day) with or without dexamethasone (0 . 25 mg/kg/ day) was administered for a period of 48 h . The ceftriaxone dose of 50 mg/kg/day was not fully effective in this model (therapeutic failure rate 28%) . With a dose of 100 mg/kg/day there were no therapeutic failures and all CSF cultures were below the level of detection at 48 h . CSF ceftriaxone concentrations, area under the time-concentration curve and time above the MIC were not significantly different with or without dexamethasone . However, concomitant use of dexamethasone resulted in higher CSF bacterial counts and a higher number of therapeutic failures (57% with the 50 mg/kg/day dose and 28% with the 100 mg/kg/day dose) . Increasing doses of ceftriaxone might be an effective mode of therapy for meningitis caused by S . pneumoniae with MIC </= 2 mg/L . However, in contrast to cephalosporin-sensitive cases, in cases caused by ceftriaxone-resistant strains, concomitant use of dexamethasone was associated with a higher failure rate even when a higher dosage of ceftriaxone was used.

J Antimicrob Chemother, 2000 Mar, 45(3), 311 - 4
Therapeutic effects of parenteral beta-lactam antibiotics on experimental otitis media caused by penicillin-resistant Streptococcus pneumoniae in guinea-pigs; Hori R et al.; The therapeutic effects of parenteral beta-lactam antibiotics were evaluated in experimental acute otitis media caused by penicillin-resistant Streptococcus pneumoniae (PRSP) in guinea-pigs . Cefotaxime, ceftriaxone and piperacillin significantly reduced viable cell counts of PRSP in the middle ear at a dose of 50 mg/kg bd for 3 days (P < 0.01 compared with control) . The therapeutic effects of cefotaxime, ceftriaxone and piperacillin were superior to those of cefotiam and ceftazidime . These therapeutic effects reflected both in vitro activity and pharmacokinetic properties of the drugs.

Clin Diagn Lab Immunol, 2000 Mar, 7(2), 314 - 7
Comparison of polymorphonuclear cells from healthy donors and differentiated HL-60 cells as phagocytes in an opsonophagocytic assay using antigen-coated fluorescent beads; Guy B et al.; Polymorphonuclear cells (PMNs) from healthy donors and differentiated HL-60 cells were compared in an opsonophagocytic assay using fluorescent latex beads coated with Streptococcus pneumoniae polysaccharide conjugates . Serum-specific phagocytosis was efficiently mediated by both sources of cells, as measured by flow cytometry, but the mean number of beads ingested per cell was three- to fivefold higher when PMNs were used than when HL-60 cells were used . Nevertheless, differentiated HL-60 cells could be a convenient and standardized source of cells to evaluate the functionality of specific antibodies to vaccine candidates as a coating on fluorescent beads.

Microb Pathog, 2000 Mar, 28(3), 135 - 44
Sequence and characterization of the glyceraldehyde-3-phosphate dehydrogenase of Mycobacterium avium: correlation with an epidermal growth factor binding protein; Parker AE et al.; Mycobacterium avium is a common pathogen in AIDS patients . The extracellular environment within the granuloma shown to support mycobacterial growth is in the caseous fluid . Previous work demonstrated that the presence of human epidermal growth factor (EGF), which is found in the tissue of chronic granulomous lesions, increases the growth rate of M . avium and Mycobacterium tuberculosis . Previously, a protein capable of binding recombinant human EGF (rEGF) in a western blot was identified with homology to glyceraldehyde-3-phosphate dehydrogenase (GAP) in both M . avium and M . tuberculosis but not Mycobacterium smegmatis . Surface GAPs have been identified in group A Streptococcus, enteropathogenic Escherichia coli, Candida albicans and Schistosoma mansoni . We have cloned the gap gene of M . avium . M . avium GAP has high homology with M . tuberculosis GAP . The protein was also expressed in M . smegmatis, conveying the ability to bind rEGF, but no growth increase was observed in 7H9 broth in the presence of rEGF up to 500 ng/ml . Only one copy of the GAP gene was identified in M . avium These results contribute to the understanding of M . avium pathogenesis by characterizing its interaction with a host protein present in the site of infection .

Anaesth Intensive Care, 2000 Feb, 28(1), 87 - 90
Streptoccocus pyogenes: a forgotten cause of severe community-acquired pneumonia; Birch C et al.; We report a case of severe community-acquired pneumonia caused by Streptococcus pyogenes (Lancefield Group A streptoccocus) that was complicated by a streptococcal toxic shock syndrome . Although this micro-organism is an uncommon cause of community-acquired pneumonia, previously well individuals may be infected and the clinical course may be fulminant . A household contact was the likely point of infection . Invasive group A streptococcal disease continues to remain an important cause of morbidity and mortality in the community and therefore will continue to be encountered by intensive care physicians . Treatment of Group A streptococcal infection remains penicillin; however, clindamycin should be added in severe infection.

Vaccine, 2000 Mar 17, 18(18), 1873 - 85
Preparation of pneumococcal capsular polysaccharide-protein conjugate vaccines utilizing new fragmentation and conjugation technologies; Pawlowski A et al.; There is a global urgent need for a new efficient and inexpensive vaccine to combat pneumococcal disease, which should also be affordable in developing countries . In view of this need a simple low-cost technique to prepare such a vaccine was developed . The preparation of serotype 14 and 23F pneumococcal capsular polysaccharide (PnPS)-protein conjugates to be included in a forthcoming multivalent PnPS conjugate vaccine is described . Commercial lots of PnPSs produced according to Good Manufacturing Practice from Streptococcus pneumoniae serotype 14 (PS14) and 23F (PS23F) were partially depolymerized by sonication or irradiation in an electron beam accelerator . The PnPS fragments were conjugated to tetanus toxoid (TT) using a recently developed conjugation chemistry . The application of these new simple, efficient and inexpensive fragmentation and conjugation technologies allowed the synthesis of several PnPS-protein conjugates containing PnPS fragments of preselected sizes and differing in the degree of substitution . The PS14TT and PS23FTT conjugate vaccine candidates were characterized chemically and their immunogenicity was evaluated in rabbits and mice . All PnPS conjugate vaccines, unlike the corresponding plain polysaccharides, produced high IgG titres in both animal species . The PS14TT conjugates tended to be more immunogenic than the PS23FTT conjugates . The immune response to the PS14TT conjugates, but not to the PS23FTT conjugates, was related to the size of the conjugated polysaccharide hapten . Both types of conjugates elicited strong booster effects upon secondary immunizations, resulting in high IgG1, IgG2a and IgG2b titres.

Vaccine, 2000 Mar 6, 18(17), 1811 - 21
Purification and characterization of Streptococcus pneumoniae palmitoylated pneumococcal surface adhesin A expressed in Escherichia coli; De BK et al.; All Streptococcus pneumoniae isolates tested to date express a species-common lipoprotein designated as pneumococcal surface adhesin A (PsaA) . This protein is cell-associated, hydrophobic, immunogenic, and genetically conserved . It is currently under investigation as a potential component in third-generation pneumococcal vaccine formulations . To overcome the problem of low-level expression of native hydrophobic PsaA in S . pneumoniae, and also of the recombinant PsaA (rPsaA) in Escherichia coli, we generated a stable E . coli construct expressing functional palmitoylated rPsaA ( approximately 10 mg/l of fermentation culture) using Borrelia burgdorferi outer surface protein A (OspA, a hydrophobic lipoprotein) signal peptide . By Western blot analysis, the chimeric rPsaA ( approximately 34 kDa) was detected in the cell lysate using anti-PsaA antibodies . It was partially purified by extracting the cell pellet with PBS/Triton X(R)-114 buffers, followed by anion exchange filter chromatography . A trypsin digestion profile of rPsaA closely resembled that of the native protein, as revealed by SDS-PAGE/silver staining . Lipidation of rPsaA was confirmed by labeling recombinant E . coli cells with {(3)H} palmitic acid and analyzing the labeled E . coli cells by Western blotting coupled with autoradiography . Further, analysis of purified rPsaA by mass spectrometry (MALDI-TOF) revealed a heterogenous spectrum with a major peak (M+H)(+1) of mass 33,384 Da (theoretical mass of palmitoylated rPsaA=33,361 Da) . Purified rPsaA was immunogenic in CBA/NCAHN-XID female mice following intranasal immunization with or without adjuvant, as determined by measurement of anti-PsaA serum IgG levels . These anti-PsaA antibodies reacted with both native and rPsaA polypeptides . Our data strongly suggest that E . coli-expressed rPsaA is palmitoylated and closely resembles the native protein in structure and immunogenicity . It was also observed to elicit measurable protection against nasopharyngeal carriage with S . pneumoniae.

Pediatrics, 2000 Mar, 105(3 Pt 1), 502 - 9
Reevaluation of outpatients with Streptococcus pneumoniae bacteremia; Bachur R et al.; BACKGROUND: The reevaluation process for outpatients recalled for Streptococcus pneumoniae bacteremia has not been standardized . Children who return ill or with new serious focal infections require admission and parenteral antibiotic therapy . Limited data exist to guide the follow-up management of those patients identified as having occult pneumococcal bacteremia . OBJECTIVES: Characterize the outcomes of outpatients with pneumococcal bacteremia based on their evaluation at follow-up . For patients who are well-appearing without serious focal infection, propose a management scheme for reevaluation . METHODS: Retrospective review of outpatients with pneumococcal bacteremia . Patients with immunocompromise, those identified with focal bacterial infection at the initial visit, or those admitted at the initial visit were excluded . Data were collected from the initial visit (when blood culture drawn) and follow-up visit with regard to clinical parameters, laboratory data, diagnoses, and any antibiotic treatment . Decision tree analysis was used to generate a model to predict children at high risk for persistent bacteremia (PB) . RESULTS: A total of 548 episodes of pneumococcal bacteremia were studied . Seventy-three children received no antibiotic, 239 oral antibiotic, and 236 parenteral antibiotic at the initial visit . Median age, temperature, and white blood cell (WBC) count were 13.5 months, 40.0 degrees C, and 20 400/mm(3) . Forty-one patients had PB or new focal infections (15 with PB alone, 4 had focal infection and PB) . Eight patients had meningitis at follow-up . Ninety-two percent returned because of notification of the positive blood culture result . A repeat blood culture was obtained in 92%, 23% had a lumbar puncture, 33% had a chest radiograph, and 12% were admitted . PB was associated with the antibiotic treatment group, elevation of temperature, and WBC count at follow-up . A simple management scheme using 2 sequential decision nodes of antibiotic treatment (none vs any) and then temperature at follow-up (>38.8 degrees C) would have predicted 16/19 patients with PB (sensitivity =.84 and specificity =.86) . CONCLUSIONS: All patients with pneumococcal bacteremia need prompt reevaluation . For well-appearing patients without new focal infection, the utility of diagnostic testing (specifically repeat blood cultures) and the need for admission may be determined by the use of antibiotics at the initial evaluation and the presence of fever at follow-up . The majority of patients can be managed as outpatients entirely . Patients who did not receive antibiotics at the initial evaluation and those treated with oral antibiotics but remain febrile are at the highest risk for persistent bacteremia.

Infection, 2000 Jan-Feb, 28(1), 58 - 9
Decreased susceptibility to extended-spectrum cephalosporins of a penicillin-susceptible Streptococcus pneumoniae in meningitis; De Champs C et al.; A 69-year-old woman was admitted to the hospital with meningitis due to Streptococcus pneumoniae . The strain was susceptible to penicillin but intermediate to cefotaxime . In Europe the decrease of susceptibility generally pertains more to penicillin than to cefotaxime . Such a strain is perhaps a forewarning of the existence of high-level cephalosporin-resistant strains . Despite the possible detection of the resistance by oxacillin disk, it underlines the need to determine the MICs of different beta-lactams without delay and to choose the most efficient treatment.

Infection, 2000 Jan-Feb, 28(1), 51 - 2
Double prosthetic valve endocarditis caused by Streptococcus pneumoniae; Claes K et al.; Infective endocarditis (IE) caused by Streptococcus pneumoniae is a rare disease . Only eight cases of pneumococcal prosthetic valve endocarditis have been described in the literature . In this report we describe the first case of pneumococcal endocarditis involving two prosthetic heart valves . The patient had pneumonia as the probable portal of entry but no predisposing conditions for invasive pneumococcal disease . Our case also illustrates the importance of transesophageal echocardiography (TEE) for the early diagnosis of IE and a timely decision for cardiac surgery.

Infection, 2000 Jan-Feb, 28(1), 13 - 20
Release of teichoic and lipoteichoic acids from 30 different strains of Streptococcus pneumoniae during exposure to ceftriaxone, meropenem, quinupristin/dalfopristin, rifampicin and trovafloxacin; Heer C et al.; The release of teichoic acids (TA) and lipoteichoic acids (LTA) from 30 different strains of Streptococcus pneumoniae during exposure to ceftriaxone, meropenem, quinupristin/dalfopristin, rifampicin and trovafloxacin at concentrations of 10 micrograms/ml and of the respective MIC was determined by an enzyme immunoassay . At 10 micrograms/ml the most rapid and intense release was detected during treatment with the beta-lactam antibiotics ceftriaxone and meropenem, the lowest release was seen with rifampicin and quinupristin/dalfopristin . Trovafloxacin delayed the release of TA/LTA . The maximum concentrations of TA/LTA, however, during trovafloxacin treatment were almost as high as those during exposure to ceftriaxone and meropenem . During exposure to the MIC, ceftriaxone, meropenem, rifampicin and trovafloxacin released significantly higher amounts of TA/LTA than during exposure to 10 micrograms/ml (p < 0.01) . Only quinupristin/dalfopristin released small amounts of TA/LTA at the low and high concentration . In conclusion, at high concentrations antibiotics that do not affect the bacterial cell wall released less pro-inflammatory compounds from S . pneumoniae than ceftriaxone and meropenem . This may be of value in the treatment of meningitis and sepsis.

Anticancer Res, 1999 Nov-Dec, 19(6C), 5511 - 4
Inhalation therapy using a streptococcal preparation (OK-432) against bronchioloalveolar carcinoma of the lung; Yano T et al.; OBJECTIVE: In order to inhibit the occurrence of airborne metastasis of bronchioloalveolar cell carcinoma (BAC), we tried to activate alveolar macrophages by the inhalation of aerosolized OK-432, which is a heat and penicillin-treated lyophilized preparation of the Su strain of Streptococcus pyogenes . METHODS AND RESULTS: Alveolar macrophages were obtained from resected specimens of lung cancer patients and cultured for 24 h in the presence of various concentrations of OK-432 (0.001-1 KE/ml) . The cytotoxic activity against a lung cancer cell line was augmented in a dose dependent manner and reached a plateau level at 0.1 KE/ml of OK-432 . Furthermore, the alveolar macrophages produced various cytokines, i.e., IL-1, TNF-alpha, and IL-6 after 72 h cultivation with 0.1 KE/ml of OK-432 . Based on the in vitro experiments, six patients with intrapulmonary metastatic BAC were therefore treated by the inhalation of aerosolized OK-432 . All 6 patients inhaled aerosolized OK-432 (0.1 KE/ml) twice a day for 5 days . The inhalation therapy regimen was repeated either weekly or monthly unless the tumor markedly progressed . No adverse events were observed in any patients . Either an augmentation of antitumor cytotoxicity or TNF-alpha production by the alveolar macrophages was observed in the two of three patients examined . CONCLUSION: OK-432 inhalation therapy was found to be safe and thus warrants further investigation to determine its clinical effectiveness for BAC.

Antonie Van Leeuwenhoek, 2000 Jan, 77(1), 21 - 30
A role for Lewis a antigens on salivary agglutinin in binding to Streptococcus mutans; Ligtenberg AJ et al.; Streptococcus mutans is a major etiological agent in dental caries . Salivary agglutinin is one of the main salivary components binding to S . mutans . To learn more about the interaction of salivary agglutinin with S . mutans, parotid, submandibular, sublingual and palatal saliva samples were incubated with S . mutans suspension . Both depleted saliva samples and bacterial extracts were analyzed by SDS-PAGE and immunoblotting . Salivary agglutinin was present in all types of glandular saliva and in all cases bound to S . mutans, also to PC337C, a P1 mutant of S . mutans . Agglutinin was separated by SDS-PAGE under reducing and non-reducing conditions and then transferred to nitrocellulose . Non-reduced agglutinin bound S . mutans, but reduced agglutinin did not . Adhesion of S . mutans to agglutinin-coated microplates was inhibited by amine-containing components, 1 M NaCl or KCl and EDTA . Adhesion decreased with decreasing pH with no adhesion below pH 5.0 . These data suggest that calcium-dependent electrostatic interactions play a role in binding . By immunoblotting was demonstrated that blood group antigens and Lewis antigens were present on agglutinin . Synthetic blood group antigens and Lewis antigens covalently coupled to polyacrylamide were tested for binding to S . mutans . Only Le(a)(Gal beta 1,3(Fuc alpha 1,4)GlcNAc) bound to S . mutans, whereas the blood group antigens Le(b), Le(x), Le(y), H1, H2, A, B and sialylated Le(a) did not . Lea without galactose (Fuc alpha 1,4GlcNAc) still bound to S . mutans, but Le(a) without fucose (Gal beta 1,3GlcNAc) did not . Binding of agglutinin to S . mutans was not inhibited by Le(a) . In conclusion, S . mutans can bind to Le(a) carbohydrate epitopes in which the fucose is an essential residue . Le(a) carbohydrate epitopes are present on salivary agglutinin but play no major role in binding.

Can J Microbiol, 1999 Dec, 45(12), 1027 - 32
Effects of iron and manganese availability on growth and production of superoxide dismutase by Streptococcus suis; Niven DF et al.; A complex medium supported good growth of the type strain of Streptococcus suis irrespective of the presence or absence of a high concentration (1 microM) of the iron chelating agent, ethylenediamine di-o-hydroxyphenylacetic acid . Good growth was also obtained using a complex medium that had been treated with Chelex-100 to reduce the iron content, but only if this medium was supplemented with manganese; supplementation with iron had little effect . Collectively, these results indicate that S . suis requires manganese, but not iron, for growth . Polyacrylamide gel electrophoresis of cell extracts followed by activity staining revealed the presence of a single manganese-cofactored superoxide dismutase; activity staining and enzyme assays revealed that manganese availability during growth affected the activity of the superoxide dismutase in cell extracts . The results are discussed with respect to the capacity of S . suis to avoid damage by reactive oxygen species.

J Clin Microbiol, 2000 Mar, 38(3), 1156 - 60
Efficacy of antimicrobial treatments and vaccination regimens for control of porcine reproductive and respiratory syndrome virus and Streptococcus suis coinfection of nursery pigs; Halbur P et al.; Seventy-six, crossbred, porcine reproductive and respiratory syndrome virus (PRRSV)-free pigs were weaned at 12 days of age and randomly assigned to seven groups of 10 to 11 pigs each . Pigs in group 1 served as unchallenged controls . Pigs in groups 2 to 7 were challenged intranasally with 2 ml of high-virulence PRRSV isolate VR-2385 (10(4.47) 50% tissue culture infective doses per 2 ml) on day 0 of the study (30 days of age) . Seven days after PRRSV challenge, pigs in groups 2 to 7 were challenged intranasally with 2 ml of Streptococcus suis serotype 2 (10(8.30) CFU/2 ml) . Group 2 pigs served as untreated positive controls . Antimicrobial treatments included daily intramuscular injection with 66,000 IU of procaine penicillin G per kg of body weight on days 8 to 10 (group 3), drinking water medication with 23.1 mg of tiamulin per kg during days 8 to 10 (group 4), and daily intramuscular injection of 5.0 mg of ceftiofur hydrochloride per kg on days 8 to 10 (group 5) . Vaccination regimens included two intramuscular doses of an autogenous killed S . suis vaccine (group 6) prior to S . suis challenge or a single 2-ml intramuscular dose of an attenuated live PRRSV vaccine (group 7) 2 weeks prior to PRRSV challenge . Mortality was 0, 63, 45, 54, 9, 40, and 81% in groups 1 to 7, respectively . Ceftiofur treatment was the only regimen that significantly (P < 0 . 05) reduced mortality associated with PRRSV and S . suis coinfection . The other treatments and vaccinations were less effective . We conclude that ceftiofur administered by injection for three consecutive days following S . suis challenge was the most effective regimen for minimizing disease associated with PRRSV and S . suis coinfection.

J Clin Microbiol, 2000 Mar, 38(3), 977 - 86
Identification of the major Spanish clones of penicillin-resistant pneumococci via the Internet using multilocus sequence typing; Zhou J et al.; Multilocus sequence typing was used to characterize isolates of the major Spanish clones of penicillin-resistant and multiple-antibiotic-resistant Streptococcus pneumoniae . Isolates of the multidrug-resistant Spanish serotype 23F clone and serotype variants of this clone either had identical allelic profiles or their allelic profiles differed from this typical allelic profile at only one of the seven housekeeping loci . Similarly, isolates of the Spanish serotype 6B and 14 clones and the penicillin-resistant serotype 9V clone (and serotype variants of this clone) each had the same allelic profiles or profiles that differed at a single locus . Multilocus sequence typing therefore allows resistant pneumococci to be assigned to the Spanish clones if they have the typical allelic profile of the clone or if their profiles differ from that profile at a single locus . A few resistant isolates that had allelic profiles typical of that of a Spanish clone or whose profiles differed from that of the typical profile at only a single locus possessed penicillin-binding protein pbp1a, pbp2b, or pbp2x genes that differed from those that are characteristic of the clone . In most cases these isolates could be assigned as variant members of the clone . Since almost all serotype 9V isolates have very similar genotypes, independently emerging penicillin-resistant clones of this serotype will inevitably appear to be similar by molecular typing procedures . Analysis of the pbp genes, in addition to multilocus sequence typing (or any other molecular typing procedure), is therefore required to assign isolates unambiguously to the penicillin-resistant Spanish serotype 9V clone.

J Oral Pathol Med, 2000 Jan, 29(1), 26 - 32
Lack of association between Streptococcus oralis and recurrent aphthous stomatitis; Riggio MP et al.; In the present study, the potential involvement of Streptococcus oralis in the aetiology of recurrent aphthous stomatitis (RAS) was investigated using the polymerase chain reaction (PCR) . Biopsies from 28 RAS patients were analysed, in addition to 20 oral lichen planus (OLP) and 13 normal biopsies that were used as controls . PCR was carried out using a primer pair that targets the D-alanine:D-alanine ligase gene and detects DNA from both S . oralis and the closely related species Streptococcus mitis . Discrimination between these two species was achieved by digestion of PCR products with the restriction endonucleases HaeIII and HindIII, which both give distinct restriction profiles for each species . S . oralis DNA was detected in 8 of 28 (29%) RAS samples, 10 of 20 (50%) OLP samples and 6 of 13 (46%) normal samples . These results suggest that S . oralis is not of primary aetiological significance in RAS.

J Heart Valve Dis, 2000 Jan, 9(1), 131 - 4
Preliminary experience with Silzone-coated St . Jude medical valves in acute infective endocarditis; Bertrand S et al.; BACKGROUND AND AIM OF THE STUDY: The rate of recurrent postoperative endocarditis after valve replacement in early-stage acute infective endocarditis is extremely high . Metallic silver coating of the sewing ring may improve the short- and long-term outcome after valve implantation . This report details our experience with the St . Jude Medical Silzone prosthesis in early surgical treatment of acute infective endocarditis . METHODS: Ten patients (mean age 66.4 years) referred for native valve or prosthetic valve endocarditis were operated on between April 1998 and June 1999 . The microorganisms responsible for the acute infection were Staphylococcus (n = 1), Streptococcus (n = 1) and Pseudomonas aeruginosa (n = 1); blood cultures remained negative in two cases . The indication for surgical treatment was related to hemodynamic condition (n = 5), a major cerebral event (stroke; n = 1), annulus abscess (n = 1), and echocardiographic evidence of large cuspal vegetations (n = 3) . All patients had received preoperative intravenous antibiotics (mean 7.8 days) . Four mitral, five aortic valve replacements, and one double mitral-aortic valve replacement, were performed after extensive debridement of the infected and necrotic tissues . Mean duration of postoperative antibiotic treatment was 32.3 days . Postoperative follow up (mean 6 months; range: 2-14.2 months) was 100% complete, and included prospective repeated transthoracic echocardiography at one week, and one, six and 12 months postoperatively . RESULTS: One patient died early in the immediate postoperative period from pneumonia and major hypoxemia . All other patients are symptom-free, without evidence of recurrent infection and perivalvular leak . CONCLUSION: Although these early results with the St . Jude Medical Silzone prosthesis require confirmation by more extensive studies, they infer that silver coating of the sewing ring may dramatically improve management of patients with active endocarditis.

Kansenshogaku Zasshi, 2000 Jan, 74(1), 1 - 5
Characterization of Streptococcus pneumoniae strains isolated from systemic infections in children; Ohkusu K et al.; Twenty-three cases of systemic pneumococcal infection diagnosed from October 1988 to September 1998 were analyzed retrospectively in order to characterize the epidemiology of systemic pneumococcal infections . The clinical diagnosis of those cases were 8 pneumonia, 8 meningitis, 3 septicemia, 3 septic arthritis, and 1 peritonitis . The patients ranged in age from 6 months to 21 years old (mean +/- SD = 3 years, 6 months +/- 5 years, 2 months), and 61% of the patients were younger than 24 months . Resistance to penicillin G (PCG) was detected in 57% of all cases . Resistance to cefotaxime (CTX), imipenem (IPM), erythromycin (EM), and clindamycin (CLDM) was 33%, 9%, 70%, and 65%, respectively . Of the 13 isolates resistant to PCG, 2 were resistant to IPM, 11 to EM and 11 to CLDM . Serotyping was performed on 17 isolates . The identified serotypes were 19 (6 isolates), 6 (5 isolates), 23 (3 isolates), 14 (2 isolates), and 5 (1 isolate) . Eleven isolates resistant to PCG were limited to serotypes 6, 19, or 23 . One patient had a recurrent episode of bacteremic pneumonia 7 months after the first episode . Streptococcus pneumoniae isolates from both episodes were compared by serotyping and pulsed-field gel electrophoresis with restriction digestion, and were confirmed as the same strain.

Br Med Bull, 1999, 55(1), 259 - 76
Antibacterial resistance in the intensive care unit: mechanisms and management; Elliott TS et al.; The incidence of multiple antimicrobial resistance of bacteria which cause infections in the intensive care unit is increasing . These include methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, penicillin-resistant Streptococcus pneumoniae and cephalosporin and quinolone resistant coliforms . More recently, pan antibiotic resistant coliforms, including carbapenems, have emerged . The rapidity of emergence of these multiple antibiotic-resistant organisms is not being reflected by the same rate of development of new antimicrobial agents . It is, therefore, conceivable that patients with serious infections will soon no longer be treatable with currently available antimicrobials . Strict management of antibiotic policies and surveillance programmes for multiple resistant organisms, together with infection control procedures, need to be implemented and continuously audited . As intensive care units provide a nidus of infection for other areas within hospitals, this is critically important for prevention of further spread and selection of these resistant bacteria.

Epidemiol Infect, 1999 Dec, 123(3), 383 - 8
Nasopharyngeal colonization of infants in southern India with Streptococcus pneumoniae; Jebaraj R et al.; To investigate the dynamics of nasopharyngeal colonization with Streptococcus pneumoniae, and to determine the prevalent serogroups/types (SGT) and their antimicrobial susceptibility, we studied 100 infants attending our well-baby clinic . Nasopharyngeal swab specimens were obtained at 6, 10, 14, 18 and 22 weeks and at 9 and 18 months of age and submitted for culture, serotyping and antimicrobial susceptibility testing of S . pneumoniae . Colonization with pneumococcus was seen on at least one occasion in 81 infants . The median age of acquisition was 11 weeks and the median duration of carriage was 1 3 months . The common SGTs identified were 6, 19, 14 and 15 . SGT 1, which was a common invasive isolate in children in our hospital during this period, was not isolated from these children . Sequential colonization by 2, 3 or 4 SGTs was observed in 18, 5 and 2 children, respectively . Resistance to penicillin, chloramphenicol, cotrimoxazole and erythromycin was observed in 0, 13 (6%) 11 (5 %) and 5 (3 %) isolates, respectively . There was a significant difference in susceptibility to cotrimoxazole between colonizing and invasive isolates (5 % vs . 40 %, P<0.0001).

Pediatr Infect Dis J, 2000 Feb, 19(2), 134 - 8
Human antibodies to pneumococcal surface protein A in health and disease; Virolainen A et al.; BACKGROUND: Diseases caused by Streptococcus pneumoniae have a high impact in young children whose ability to mount antibodies to capsular polysaccharides is impaired . Pneumococcal surface protein A (PspA) is a potential vaccine candidate for this age group . METHODS: We used Western blot analysis and enzyme immunoassay to study human sera of healthy adults from Alabama (n = 20) and from Finland (n = 21), healthy children from Finland (n = 20) and ill children from Finland, those with pneumococcal invasive infection (n = 26) and those with nonpneumococcal invasive infection (n = 26) . RESULTS: Human antibodies to PspA exhibited strong cross-reactivity among different pneumococcal strains . The geometric mean titer of IgG antibody to PspA in sera from 21 healthy adults was 4,040, from ten 3-year-old healthy children 1,080 and from ten 2-month-old healthy children 1,650 . The geometric mean titer of PspA antibody of acute phase sera of children with invasive pneumococcal disease was 140, significantly (P < 0.001) lower than the respective value, 1,020, for children with infection caused by other bacteria . CONCLUSIONS: We demonstrate for the first time the existence of antibodies to PspA in human sera in health and disease . The findings in ill children suggest that antibodies to PspA might play a role in protection against pneumococcal disease.

Clin Transplant, 2000 Feb, 14(1), 61 - 5
Immunization of renal transplant recipients with pneumococcal polysaccharide vaccine; Kazancioglu R et al.; BACKGROUND: Streptococcus pneumoniae, a common pathogen leading to pneumonia, is a cause of morbidity and mortality in immunosuppressed patients . Vaccination against this agent can be recommended for immunosuppressed patients, including those with chronic renal failure, nephrotic syndrome and renal transplant recipients; however, a diminished immune response and loss of protective antibodies have been observed . PATIENTS AND METHODS: In our prospective study, the efficacy and side effects of polyvalent pneumococcal vaccination were investigated in renal transplant recipients . A total of 21 patients (6 female, 15 male) with well-functioning renal allografts, who had transplant surgery at least 2 months before, were included in the study . The patients were stratified according to the immunosuppressive protocol and 8 received double, while 13 received triple, immunosuppressive agents . After obtaining basal serum samples, all cases were vaccinated with the 0.5 mL intramuscular administration of polyvalent polysaccharide pneumococcal vaccine (Pneumo 23 Pasteur Merieux, lot No: K 1131) . RESULTS: Following a mean of 6 wk in all patients and also a mean of 12 wk in 12 patients, serum samples were again obtained to measure pneumococcal antibodies . Antibody titers following 6 and 12 wk of vaccination were significantly higher, as compared with basal values in all patients, except one . These titers did not show any statistically significant difference between double and triple therapies . There was no significant difference between the 12th and 6th wk postvaccination antibody titers . No systemic or local adverse effects were observed . CONCLUSION: Pneumococcal vaccination is safe and effective in patients with well-functioning renal allografts, at least in the short term . This vaccination policy may be useful for preventing invasive pneumococcal disease in immunosuppressed patients.

J Oral Sci, 1999 Dec, 41(4), 169 - 72
The phenomenon of salivary protein adsorption onto Streptococcus mitis ATCC 903 cells; Tamura M et al.; It is thought that salivary proteins on bacterial cells have some influence on the adhesion of oral bacteria onto the surface of oral tissues and on bacterial aggregation . Initially, this study sought to examine the phenomenon of salivary protein adsorption to the surface of Streptococcus mitis ATCC 903 using 3H-labeled salivary proteins . We investigated the effects of hydrophobic level and lectin-ligand binding on adsorption of salivary proteins, and also the influence of cell surface components on adsorption . The results showed that the adsorption of salivary proteins was clearly reduced by the presence of Tween 20, LiCl, NaSCN, Hexadecane and some sugars . The adsorption was also affected by the pH level, and protease treatment or heat treatment of cells also decreased the volume of adsorbed proteins . Although the adsorption of proteins onto heat-treated cells was dramatically reduced by the presence of LiCl and NaSCN, the presence of sugars had little influence on this adsorption . These findings suggest that the main adsorption of salivary proteins is due to hydrophobic factors, and the heat-sensitive surface components of the cells had some relation to lectin-ligand binding . Therefore, it appears important to study the adsorption of salivary proteins onto cells since the salivary proteins on bacterial cells play an important role in their adherence to the saliva-coated oral tissues and bacterial aggregation.

J Bacteriol, 2000 Mar, 182(6), 1529 - 40
The RofA binding site in Streptococcus pyogenes is utilized in multiple transcriptional pathways; Granok AB et al.; Understanding the regulation of adhesins defines a pathogenic bacterium's interaction with the local environment within the host . In certain strains of Streptococcus pyogenes, transcription of prtF, the gene which encodes the fibronectin-binding adhesin protein F, is activated by RofA under anaerobic conditions . RofA binds specifically to DNA in its target promoters and autoregulates its own expression . In this study, we have used DNase I protection assays to further investigate the interaction of RofA with its target promoters . In the region between rofA and the gene which encodes protein F (prtF), RofA binds to two distinct sites: a smaller site (17 bp) adjacent to the rofA promoter, and a larger site (40 bp) adjacent to the prtF promoter . Analysis of fusions to a novel reporter gene whose product consists of the fusion of the N-terminal secretion domain of protein F with the C-terminal enzymatic domain of the enterococcal alkaline phosphatase (PhoZ) revealed that the small RofA binding site had no direct role in control of prtF transcription but contributed to regulation of rofA . Comparison in several strains representing different patterns of prtF expression indicated that the larger site was required for activation of rofA and of prtF in all strains by both RofA-dependent and -independent pathways . Thus, it would appear that a common recognition sequence provides separate entries to a final common pathway in S . pyogenes virulence gene expression . The identification of multiple RofA-like proteins and promoters with RofA binding sites implies the existence of a widespread interacting regulatory network.

Drugs Aging, 1999, 15 Suppl 1, 11 - 9
Epidemiology of pneumococcal infections in the elderly; Butler JC et al.; The risk of invasive Streptococcus pneumoniae infection (primarily bacteraemia and meningitis) is greatest among the very young and the very old . Persons in certain racial groups, including African-Americans, American Indians, Native Alaskans and Australian Aborigines, are also at increased risk of disease . Other factors that appear to increase the risk of pneumococcal infection are lower socioeconomic status, recent infection with influenza and possibly other viral respiratory tract infections, chronic medical conditions, and immunosuppressive medications . Reported annual incidences of invasive pneumococcal disease among persons aged > or = 65 years in North America and Europe range from 25 to 90 cases/100,000 persons . In the US and Canada, these rates represent between 15,000 and 30,000 cases annually among the elderly . Mortality caused by pneumococcal infections is highest among the elderly, with nearly 1 in 5 cases resulting in death . Worldwide, S . pneumoniae is the leading cause of community-acquired pneumonia requiring hospitalisation . The high fatality rates, as well as recent outbreaks of pneumococcal infection among unvaccinated nursing home residents and the emergence of drug-resistant pneumococcal strains, highlight the importance of preventing invasive infection by vaccination.

J Vet Diagn Invest, 2000 Jan, 12(1), 21 - 7
Coinfection by porcine circoviruses and porcine parvovirus in pigs with naturally acquired postweaning multisystemic wasting syndrome; Ellis JA et al.; Postweaning multisystemic wasting syndrome (PMWS) is an emerging disease in swine . Recently, the disease has been reproduced with inocula containing a newly described porcine circovirus (PCV), designated PCV 2, and porcine parvovirus (PPV) . In order to determine if these viruses interact in naturally acquired PMWS, affected tissues from field cases were examined by immunohistochemistry (IHC) and polymerase chain reaction (PCR) for PCV 2 and PPV, as well as by PCR for the other recognized porcine circovirus, PCV 1 . Porcine circovirus 2 was detected by PCR or IHC in affected fixed or frozen tissues from 69 of 69 cases of PMWS collected over 3 years from 25 farms . Porcine parvovirus was detected in 12 of the same cases, and PCV 1 was detected in 9 of 69; however, an apparent decrease was found in the sensitivity of the PCRs used to detect the latter 2 viruses when fixed tissue from the same cases were compared with the use of frozen tissues . Porcine circovirus 2 was not detected by PCR in affected tissues from 16 age-matched pigs that had Streptococcus suis-associated disease . Electron microscopic examination of plasma pooled from 15 pigs with PMWS revealed the presence of PCV and PPV, whereas these viruses were not observed in pooled plasma from 5 age-matched clinically normal pigs . These results confirm and extend previous findings documenting a consistent association of PCV 2 with PMWS . As well, infection by PPV or PCV 1 or both may be an important cofactor in the pathogenesis of some, but apparently not all, cases of PMWS.

Mol Med Today, 2000 Mar, 6(3), 125 - 32
Superantigens - powerful modifiers of the immune system; Fraser J et al.; Superantigens are powerful microbial toxins that activate the immune system by binding to class II major histocompatibility complex and T-cell receptor molecules . They cause a number of diseases characterized by fever and shock and are important virulence factors for two human commensal organisms, Staphylococcus aureus and Streptococcus pyogenes, as well as for some viruses . Their mode of action and variation around the common theme of over-stimulating T cells, provides a rich insight into the constant battle between microbes and the immune system.

FEMS Microbiol Lett, 2000 Mar 1, 184(1), 17 - 21
Signal sequence and alanine-rich region of streptococcal protein antigen A of Streptococcus sobrinus can direct localization of alkaline phosphatase to the periplasm of Escherichia coli; Holt RG et al.; Streptococcal protein antigen A (SpaA) of Streptococcus sobrinus is expressed on the surface of cells and extracellularly . TnphoA which lacks signals for transcription and membrane transport of Escherichia coli alkaline phosphatase was used to analyze the sequences necessary for transport of a SpaA/PhoA fusion protein across the cytoplasmic membrane to the periplasm of E . coli cells . Of 15 alkaline phosphatase-producing isolates analyzed, all were found to localize more than 85% of the SpaA/PhoA hybrid protein to the periplasm of E . coli cells . From DNA sequence analysis, all were found to have TnphoA inserted into an identical site . The insertion site of TnphoA was downstream from the coding sequence that generates four tandemly repeated alanine-rich sequences of 82 amino acid residues . These results suggest that in addition to the signal sequence, mature protein sequences containing alanine-rich repeat sequences may play a role in the export of the SpaA protein across a bacterial membrane.

Infect Immun, 2000 Mar, 68(3), 1569 - 73
Immune responses to specific antigens of Streptococcus pneumoniae and Moraxella catarrhalis in the respiratory tract; Samukawa T et al.; Streptococcus pneumoniae and Moraxella catarrhalis are two common respiratory pathogens, colonizing as many as 54 and 72% of children, respectively, by 1 year of age . The immune responses to surface protein A of S . pneumoniae (PspA) and the high-molecular-weight outer membrane protein of M . catarrhalis (UspA) in the sera of various age groups in the general population and in the nasopharynges of 30 children monitored from birth through 1 year of age were evaluated . Immunoglobulin G (IgG) was the dominant serum antibody to PspA and UspA . Whereas the serum antibody response to PspA peaked in childhood, the antibody response to UspA peaked in adulthood . In the first 2 years of life, comparable amounts of IgM and IgG antibodies to both proteins were observed . In older persons, IgG antibodies to both antigens predominated over IgM antibodies . The levels of IgA antibody to these antigens in serum remained low during the first 2 years of life . The levels of IgM antibody to the two antigens in serum exceeded the levels of IgA antibody to the same two antigens throughout life . Although IgA was the dominant antibody to PspA and UspA in airway secretions, it was detected in a minority of the children (3 of 15 for PspA and 0 of 15 for UspA) . Even the majority of the children previously colonized with these pathogens lacked antibody to them in their secretions.

Infect Immun, 2000 Mar, 68(3), 1557 - 62
Relative roles of pneumolysin and hydrogen peroxide from Streptococcus pneumoniae in inhibition of ependymal ciliary beat frequency; Hirst RA et al.; Ciliated ependymal cells line the ventricular system of the brain and the cerebral aqueducts . This study characterizes the relative roles of pneumolysin and hydrogen peroxide (H(2)O(2)) in pneumococcal meningitis, using the in vitro ependymal ciliary beat frequency (CBF) as an indicator of toxicity . We have developed an ex vivo model to examine the ependymal surface of the brain slices cut from the fourth ventricle . The ependymal cells had cilia beating at a frequency of between 38 and 44Hz . D39 (wild-type) and PLN-A (pneumolysin-negative) pneumococci at 10(8) CFU/ml both caused ciliary slowing . Catalase protected against PLN-A-induced ciliary slowing but afforded little protection from D39 . Lysed PLN-A did not reduce CBF, whereas lysed D39 caused rapid ciliary stasis . There was no effect of catalase, penicillin, or catalase plus penicillin on the CBF . H(2)O(2) at a concentration as low as 100 microM caused ciliary stasis, and this effect was abolished by coincubation with catalase . An additive inhibition of CBF was demonstrated using a combination of both toxins . A significant inhibition of CBF at between 30 and 120 min was demonstrated with both toxins compared with either H(2)O(2) (10 microM) or pneumolysin (1 HU/ml) alone . D39 released equivalent levels of H(2)O(2) to those released by PLN-A, and these concentrations were sufficient to cause ciliary stasis . The brain slices did not produce H(2)O(2), and in the presence of 10(8) CFU of D39 or PLN-A per ml there was no detectable bacterially induced increase of H(2)O(2) release from the brain slice . Coincubation with catalase converted the H(2)O(2) produced by the pneumococci to H(2)O . Penicillin-induced lysis of bacteria dramatically reduced H(2)O(2) production . The hemolytic activity released from D39 was sufficient to cause rapid ciliary stasis, and there was no detectable release of hemolytic activity from the pneumolysin-negative PLN-A . These data demonstrate that D39 bacteria released pneumolysin, which caused rapid ciliary stasis . D39 also released H(2)O(2), which contributed to the toxicity, but this was masked by the more severe effects of pneumolysin . H(2)O(2) released from intact PLN-A was sufficient to cause rapid ciliary stasis, and catalase protected against H(2)O(2)-induced cell toxicity, indicating a role for H(2)O(2) in the response . There is also a slight additive effect of pneumolysin and H(2)O(2) on ependymal toxicity; however, the precise mechanism of action and the role of these toxins in pathogenesis remain unclear.

Infect Immun, 2000 Mar, 68(3), 1450 - 6
CpG oligodeoxynucleotides act as adjuvants for pneumococcal polysaccharide-protein conjugate vaccines and enhance antipolysaccharide immunoglobulin G2a (IgG2a) and IgG3 antibodies; Chu RS et al.; Pneumococcal polysaccharide-protein conjugate vaccines elicit antipolysaccharide antibodies, but multiple doses are required to achieve protective antibody levels in children . In addition, the immunogenicity of experimental multivalent pneumococcal conjugate vaccines varies with different polysaccharide serotypes . One strategy to improve these vaccines is to incorporate an adjuvant to enhance their immunogenicity . Synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN) are adjuvants that promote T-cell and T-dependent antibody responses to protein antigens, but it has been unclear whether CpG ODN can enhance polysaccharide-specific antibody responses . The present studies demonstrate significant adjuvant activity of CpG ODN for antibody responses against Streptococcus pneumoniae polysaccharide types 19F and 6B induced by conjugates of 19F and 6B with the protein carrier CRM(197) . BALB/c ByJ mice were injected with 19F-CRM(197) or 6B-CRM(197) with or without CpG ODN, and sera were tested for anti-19F or anti-6B antibodies by enzyme-linked immunosorbent assay . The polysaccharide-specific antibody response to 19F-CRM(197) alone was predominantly of the immunoglobulin G1 (IgG1) and IgM isotypes, but addition of CpG ODN markedly increased geometric mean titers of total anti-19F antibody (23-fold), anti-19F IgG2a (26-fold), and anti-19F IgG3 (>246-fold) . The polysaccharide-specific antibody response to 6B-CRM(197) alone consisted only of IgM, but addition of CpG ODN induced high titers of anti-6B IgG1 (>78-fold increase), anti-6B IgG2a (>54-fold increase), and anti-6B IgG3 (>3,162-fold increase) . CpG ODN also increased anti-CRM(197) IgG2a and IgG3 . Adjuvant effects were not observed with control non-CpG ODN . Thus, CpG ODN significantly enhance antipolysaccharide IgG responses (especially IgG2a and IgG3) induced by these glycoconjugate vaccines.

Infect Immun, 2000 Mar, 68(3), 1374 - 82
Genetic relationships between clinical isolates of Streptococcus pneumoniae, Streptococcus oralis, and Streptococcus mitis: characterization of "Atypical" pneumococci and organisms allied to S . mitis harboring S . pneumoniae virulence factor-encoding genes; Whatmore AM et al.; The oral streptococcal group (mitis phylogenetic group) currently consists of nine recognized species, although the group has been traditionally difficult to classify, with frequent changes in nomenclature over the years . The pneumococcus (Streptococcus pneumoniae), an important human pathogen, is traditionally distinguished from the most closely related oral streptococcal species Streptococcus mitis and Streptococcus oralis on the basis of three differentiating characteristics: optochin susceptibility, bile solubility, and agglutination with antipneumococcal polysaccharide capsule antibodies . However, there are many reports in the literature of pneumococci lacking one or more of these defining characteristics . Sometimes called "atypical" pneumococci, these isolates can be the source of considerable confusion in the clinical laboratory . Little is known to date about the genetic relationships of such organisms with classical S . pneumoniae isolates . Here we describe these relationships based on sequence analysis of housekeeping genes in comparison with previously characterized isolates of S . pneumoniae, S . mitis, and S . oralis . While most pneumococci were found to represent a closely related group these studies identified a subgroup of atypical pneumococcal isolates (bile insoluble and/or "acapsular") distinct from, though most closely related to, the "typical" pneumococcal isolates . However, a large proportion of isolates, found to be atypical on the basis of capsule reaction alone, did group with typical pneumococci, suggesting that they have either lost capsule production or represent as-yet-unrecognized capsular types . In contrast to typical S . pneumoniae, isolates phenotypically identified as S . mitis and S . oralis, which included isolates previously characterized in taxonomic studies, were genetically diverse . While most of the S . oralis isolates did fall into a well-separated group, S . mitis isolates did not cluster into a well-separated group . During the course of these studies we also identified a number of potentially important pathogenic isolates, which were frequently associated with respiratory disease, that phenotypically and genetically are most closely related to S . mitis but which harbor genes encoding the virulence determinants pneumolysin and autolysin classically associated with S . pneumoniae.

Infect Immun, 2000 Mar, 68(3), 1215 - 21
Role of group A streptococcal virulence factors in adherence to keratinocytes; Darmstadt GL et al.; To evaluate the role of putative group A streptococcal virulence factors in the initiation of skin infections, we compared the adherence of a wild-type M49-protein skin-associated strain to that of a series of 16 isogenic mutants created by insertional inactivation of virulence genes . None of the mutants, including the M-protein-deficient (emm mutant) strain, displayed reduced adherence to early-passage cultured human keratinocytes, but adherence of the mutant lacking hyaluronic acid capsule expression (has mutant) was increased 13-fold . In contrast, elimination of capsule expression in M2-, M3-, and M18-protein has mutants increased adherence only slightly (1.3- to 2.3-fold) compared to their respective wild-type strains . A mutant with inactivation of both emm and has displayed high-level adherence (34.9 +/- 4.1%) equal to that of the has mutant strain (40.7 + 8.0%), confirming the lack of involvement of M49 protein in attachment . Moreover, adherence of the M49-protein-deficient (emm mutant) and wild-type strains was increased to the same level (57 and 55%, respectively) following enzymatic digestion of their hyaluronic acid capsule . Adherence of mutants lacking oligopeptide permease (Opp) expression was increased 3.8- to 5.5-fold, in association with decreased cell-associated hyaluronic acid capsule . Finally, soluble CD46 failed to inhibit adherence of M49- and M52-serotype skin strains . We conclude that (i) bacterial M protein and keratinocyte CD46 do not mediate adherence of M49 skin-associated Streptococcus pyogenes to epidermal keratinocytes, (ii) hyaluronic acid capsule impedes the interaction of bacterial adhesins with keratinocyte receptors, (iii) modulation of capsule expression may be important in the pathogenesis of skin infections, and (iv) the molecular interactions in attachment of skin strains of S . pyogenes to keratinocytes are unique and remain unidentified.

Infect Immun, 2000 Mar, 68(3), 1019 - 25
Allele substitution of the streptokinase gene reduces the nephritogenic capacity of group A streptococcal strain NZ131; Nordstrand A et al.; To investigate the role of allelic variants of streptokinase in the pathogenesis of acute poststreptococcal glomerulonephritis (APSGN), site-specific integration plasmids were constructed, which contained either the non-nephritis-associated streptokinase gene (skc5) from the group C streptococcal strain Streptococcus equisimilis H46A or the nephritis-associated streptokinase gene (ska1) from the group A streptococcal nephritogenic strain NZ131 . The plasmids were introduced by electroporation and homologous recombination into the chromosome of an isogenic derivative of strain NZ131, in which the streptokinase gene had been deleted and which had thereby lost its nephritogenic capacity in a mouse model of APSGN . The introduction of a non-nephritis-associated allelic variant of streptokinase did not rescue the nephritogenic capacity of the strain . The mutant and the wild-type strains produced equivalent amounts of streptokinase . Complementation of the ska deletion derivative with the original ska allele reconstituted the nephritogenicity of wild-type NZ131 . The findings support the hypothesis that the role of streptokinase in the pathogenesis of APSGN is related to the allelic variant of the protein.

Clin Ther, 2000 Jan, 22(1), 29 - 39
Antimicrobial therapy of acute otitis media: review of treatment recommendations; Aronovitz GH; OBJECTIVE: This paper reviews 3 previously published articles that provided recommendations for antimicrobial therapy of acute otitis media (AOM) and combines them to provide revised recommendations . BACKGROUND: AOM is one of the most common pediatric infections requiring a prescription for an antimicrobial agent . The optimal approach to treatment of AOM requires early, efficacious, and practical therapy . Several experts and organizations have developed recommendations for the management of AOM, but the number of these may overwhelm the busy primary care practitioner . A MEDLINE search of the pediatric and infectious disease literature on AOM treatment recommendations was used to select 3 representative, previously published articles for this review . When selecting an agent, physicians should consider in vitro activity, particularly against drug-resistant Streptococcus pneumoniae; pharmacokinetics; adverse events; palatability of the suspension; and cost . In addition, physicians' clinical experience is an important determinant . CONCLUSIONS: Amoxicillin is recommended as the first-line agent to treat uncomplicated AOM . For clinical treatment failures after 3 days of amoxicillin, recommended antimicrobial agents include oral amoxicillin/clavulanate, cefuroxime axetil, cefprozil, cefpodoxime proxetil, and intramuscular (i.m.) ceftriaxone . I.m . ceftriaxone should be reserved for severe cases or patients in whom noncompliance is expected . Tympanocentesis for identification of pathogens and susceptibility to antimicrobial agents is recommended for selection of third-line agents.

Clin Ther, 2000 Jan, 22(1), 2 - 14
Comparison of bacteriologic eradication of Streptococcus pneumoniae by clarithromycin and reports of increased antimicrobial resistance; Gotfried MH; OBJECTIVE: To determine whether reported increases in Streptococcus pneumoniae resistance, as determined by in vitro antimicrobial susceptibility testing, correlate with the clinical efficacy of clarithromycin in treating patients with acute exacerbations of chronic bronchitis (AECB) or community-acquired pneumonia (CAP) . BACKGROUND: Surveillance data on antimicrobial resistance suggest that the overall rate of S . pneumoniae resistance in vitro in the United States has increased to approximately 45% during the past decade . S . pneumoniae is showing increased resistance to penicillin, other beta-lactams, and macrolides . Despite this increased resistance, the clinical efficacy of clarithromycin does not appear to be diminished to the degree suggested by reported resistance rates . The author examined several studies of clarithromycin in patients with AECB or CAP that demonstrate S . pneumoniae eradication rates in vivo of approximately 92% . The discordance between reported increases in resistance of S . pneumoniae isolates in vitro and the eradication rate with clarithromycin in vivo is discussed in light of 5 observations . RESULTS: First, surveillance data on S . pneumoniae resistance rates to clarithromycin may be overestimated . Second, efflux mutant strains may not be clinically resistant . Third, host immune defenses play a role in treatment outcomes . Fourth, in vitro resistance may not correlate with in vivo clinical success . Finally, clarithromycin and its active metabolite, 14-OH-clarithromycin, attain high concentrations in patients . CONCLUSION: Reported increases in the prevalence of S . pneumoniae resistance do not appear to have had proportional effects on the clinical efficacy of clarithromycin in the treatment of patients with AECB or CAP caused by S . pneumoniae.

Ostomy Wound Manage, 1999 Oct, 45(10), 50 - 4, 56-8
The effects of UVC irradiation on group A streptococcus in vitro; Sullivan PK et al.; Streptococcus pyogenes (group A streptococcus--GAS) is a common cause of necrotizing fasciitis (NF)--a severe infection of the subcutaneous soft tissue . The purpose of this study was to determine if the topical therapy ultraviolet light C (UVC) is effective in killing GAS in vitro and to evaluate the most effective treatment parameters for use with UVC therapy . Five replications of GAS at 10(8) organisms/mL were plated . The cultures were treated with a UVC light 1 inch from the surface . Irradiation times were as follows: 0, 2, 3, 4, 5, 15, 30, 45, 60, 90, 120, and 180 seconds . Bacterial cultures were incubated and colony counts performed . A second set of GAS cultures were exposed to UVC for 30, 90, and 120 seconds either once daily (qd) or twice daily (bid) . Kill rates were 99.9% for GAS at 4 seconds to 180 seconds . Kill rates of 99.9% were also obtained at 30 seconds and 90 seconds when UVC treatment was given either qd or bid . This data indicates that UVC is bactericidal for GAS at times as short as 4 seconds . In addition, UVC treatment was not effective when administered through thin film dressings.

J Endod, 1999 Oct, 25(10), 653 - 9
Bacterial microleakage of Cavit, IRM, TERM, and Fermit: a 21-day in vitro study; Deveaux E et al.; The aim of our study was to evaluate the leakage of four cements (Cavit, IRM, TERM, and Fermit) using a two-compartment model system and Streptococcus sanguis as bacterial marker . Access cavities in premolars were filled with cement and the teeth immersed in culture medium in the model system . Half of the teeth were thermocycled on day 2 . Bacterial percolation into the upper compartment was measured at regular intervals (days 2, 7, 14, and 21) . Cement thickness was measured at the end of the study . In the nonthermocycled group, Cavit was more leakproof than the other cements at day 2 (p = 0.011), than TERM and IRM at day 7 (p = 0.043) . Fermit was more leakproof than IRM at day 7 (p = 0.043) . In the thermocycled group, Cavit was more leakproof than the other cements at day 7 (p = 0.041) . Thermocycling did not significantly affect leakage . Cement thickness averaged 4.1 mm and did not significantly affect leakage . These results should be considered when using cements as temporary fillings.

Gen Dent, 1999 Mar-Apr, 47(2), 187 - 90
Antimicrobial activity of cavity disinfectants; Gultz J et al.; The purpose of this study was to determine the antimicrobial activity of four commercially available cavity disinfectants and one prescription mouthwash as they came into contact with bacteria commonly found in the oral cavity . Streptococcus mutans, salivarius, and Actinomyces viscosus were used in the study . Zones of microbial inhibition were measured in millimeters after 48 hours . The results of this study indicate that all of the antimicrobial agents demonstrated activity against the bacteria tested . Consepsis Solution produced the largest zones of inhibition against all three of the bacteria used.

Clin Chim Acta, 2000 Feb 25, 292(1-2), 1 - 12
Glutamine synthetase in experimental meningitis: increased ratio of the subunits 3 and 2 may indicate enhanced activity; Smirnov AV et al.; Glutamine synthetase (GS) activity is higher in the neocortex but not in the hippocampal formation of rabbit brain during Streptococcus pneumoniae meningitis compared to the respective brain region of uninfected control animals . One-dimensional polyacrylamide gel electrophoresis (1D-SDS-PAGE) revealed an apparent molecular mass (M(r)) of 44000 Dalton (Da) for GS from rabbit brain . After two-dimensional gel electrophoresis (2D-PAGE), followed by Coomassie-blue staining, GS separated into three distinct spots (S1, S2, S3) . One additional spot (S4) occurred on the immunoblot . All four GS spots exhibited the same M(r) (44000 Da), but differed in their isoelectric points . Densitometric evaluation of the two-dimensional maps revealed a strong increase of optical density (OD) of S3 in the frontal cortex of infected animals . The calculated OD ratio S3/S2 in the frontal cortex from rabbits with meningitis was 1.75+/-0.68 (mean+/-standard deviation) . Compared to controls (0 . 85+/-0.39), this value was significantly increased (p=0.0006) . In the hippocampal formation, the ratio S3/S2 was nearly unchanged during meningitis . It is suggested that the ratio S3/S2 may indicate a neuroprotective feature of rabbit brain during meningitis since neuronal apoptosis occurs only in the dentate gyrus and not in the frontal cortex.

Am J Vet Res, 2000 Feb, 61(2), 162 - 6
Comparison of the phenotypes of Streptococcus zooepidemicus isolated from tonsils of healthy horses and specimens obtained from foals and donkeys with pneumonia; Anzai T et al.; OBJECTIVE: To determine whether streptococcal pneumonia is caused by strains of Streptococcus zooepidemicus similar to those obtained from the tonsils of healthy horses . SAMPLE POPULATION: 5 tonsils from healthy horses, 8 tracheal washes and 6 lung specimens from foals with pneumonia, and 5 nasopharyngeal swab specimens from donkeys with acute bronchopneumonia . PROCEDURE: Variable M-like protectively immunogenic SzP proteins of 5 isolates of S . zooepidemicus from each tonsil and clinical specimen were compared, using immunoblots . The SzP gene of 13 isolates representative of various SzP immunoblot phenotypes from 1 healthy horse and 9 horses and donkeys with pneumonia were sequenced and compared . Cell-associated hyaluronic acid concentration and resistance to phagocytosis of some isolates were measured . RESULTS: Tonsils of each healthy horse were colonized by several SzP phenotypes similar to those of foals or donkeys with pneumonia . In contrast, multiple isolates from animals with pneumonia had the same SzP phenotype, indicating infection by a single strain or clone . Analysis of the SzP sequence confirmed that differences in immunoblot phenotype were associated with sequence differences and that several SzP genotypes were in healthy horses and animals with pneumonia . Isolates with high concentrations of cell-associated hyaluronic acid were more resistant to phagocytosis . CONCLUSIONS AND CLINICAL RELEVANCE: An SzP-specific immunoblot is a useful, sensitive measure of diversity among strains of S . zooepidemicus . Single strains with SzP phenotypes similar to those found in tonsils of healthy horses cause pneumonia . Because of the diversity of SzP phenotype and genotype among isolates from animals with pneumonia, SzP phenotype is not an important determinant of invasiveness or epizootic capabilities.

J Perinatol, 1999 Jul-Aug, 19(5), 337 - 42
Group B streptococcus: to culture or not to culture?
Katz PF, Hibbard JU, Ranganathan D, Meadows W, Ismail M.
OBJECTIVE: To determine if universal Group B Streptococcus (GBS) culturing and antibiotic prophylaxis of obstetric patients decreased the incidence of neonatal early-onset GBS sepsis and mortality and maternal chorioamnionitis . STUDY DESIGN: A time series observational study was conducted to compare the cohort of all obstetric patients delivering at the University of Chicago neonatal center from January 1989 through December 1993, before a GBS surveillance policy existed, with the cohort delivering January 1994 through December 1996, after initiation of a GBS policy . Included in the policy were universal GBS cultures at 28 weeks' gestation, antibiotic prophylaxis at the time of labor for all those with positive cultures and for all with risk factors of preterm delivery, preterm premature rupture of membranes, prolonged rupture of membranes greater than 18 hours, and a previous child affected by GBS or maternal fever in labor . Predictor variables were GBS culturing and antibiotic usage; outcome variables were incidence of GBS sepsis and mortality in the neonates and maternal chorioamnionitis . chi-squared and Fisher exact analyses were used with p < 0.05 being significant . RESULTS: Before the GBS policy, there were 16,272 deliveries with a 2.24/1000 deliveries rate of early-onset GBS sepsis (n = 35); after initiating the GBS policy, 9130 deliveries occurred with an early-onset GBS sepsis rate of 2.29/1000 (n = 20) . Early-onset GBS sepsis case fatality rates before and after initiation of the policy were 14.3% and 0%, respectively (p = 0.09) . Antibiotic use almost doubled (relative risk = 1.84; confidence interval, 1.74 to 1.93, p < 0.001) over the two time periods, and the relative risk of chorioamnionitis decreased to 0.95 (confidence interval, 0.73 to 0.99, p = 0.04) . CONCLUSION: Despite universal GBS culturing and very liberal use of antibiotics in labor, we were unable to effect a statistically significant change in the rate of early-onset GBS sepsis or mortality, and there was only a slightly decreased chorioamnionitis rate.

Res Vet Sci, 2000 Feb, 68(1), 33 - 9
Determination of intraspecies variations of the V2 region of the 16S rRNA gene of Streptococcus equi subsp . zooepidemicus; Abdulmawjood A et al.; The 16S rRNA gene of 39 S . equi subsp . zooepidemicus strains and two S . equi subsp . equi strains was amplified by polymerase chain reaction and subsequently digested with the restriction enzyme Hinc II . A restriction profile with two fragments with sizes of 1250 bp and 200 bp could be observed for both S . equi subsp . equi strains and for 30 of the 39 S . equi subsp . zooepidemicus strains indicating a sequence variation within the V2 region of the 16S rRNA gene of the remaining nine S . equi subsp . zooepidemicus isolates . A segment of the 16S rRNA gene including the hypervariable V2 region of 11 S . equi subsp . zooepidemicus and two S . equi subsp . equi could be amplified by PCR and sequenced . The sequence of the V2 region of eight S . equi subsp . zooepidemicus strains appeared to be identical or almost identical to the sequence of the two S . equi subsp . equi strains . The sequence of the remaining three S equi subsp . zooepidemicus strains differed significantly from the sequence of S . equi subsp . equi . These differences allowed a division of S . equi subsp . zooepidemicus strains into two 16S rRNA types and might possibly have consequences for the taxonomic position of these phenotypically indistinguishable strains of one subspecies . A molecular typing could additionally be performed by amplification of the gene encoding the 16S-23S rRNA spacer region . A single amplicon of the spacer gene of 1100 bp could be observed for one S . equi subsp . zooepidemicus, an amplicon of 950 bp for two S . equi subsp . equi strains and 10 S . equi subsp . zooepidemicus strains, a amplicon of 780 bp for 27 S . equi subsp . zooepidemicus strains and a single amplicon of 600 bp for one S . equi subsp . zooepidemicus strain . The variations of the V2 region of the 16S rRNA gene and the size variations of the 16S-23S rRNA spacer gene were not related to each other . Both variations could be used for molecular typing of this species, possibly useful in epidemiological aspects .

Biopolymers, 2000 Apr 5, 53(4), 281 - 92
Synthesis, microbicidal activity, and solution structure of the dodecapeptide from bovine neutrophils; Raj PA et al.; The dodecapepetide sequence R-L-C-R-I-V-V-I-R-V-C-R with a disulfide bridge between the cysteine residues found in bovine neutrophils was synthesized by solid-phase procedures . Its antimicrobial activity against oral microorganisms such as Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Streptococcus mutans, and Streptococcus gordonii was examined, and its structural features were examined by CD and determined by two-dimensional (2D) nmr . The strains P . gingivalis (W50 and 381), A . actinomycetemcomitans (Y4 and 67), S . gordonii (DL1), and S . mutans (GS5) are found to be highly sensitive to this peptide at 2-2.5 microM concentrations, suggesting that the dodecapeptide is a potent antibiotic for oral pathogens . The weak negative n-sigma* band observed at approximately 265-270 nm in the CD spectra of this peptide provides evidence for the presence of a disulfide bridge . The negative n-pi* band at approximately 200 nm and the positive pi-pi* band at 185 nm suggest a folded structure for this peptide . The negative n-pi* shifts from 200 to 206 nm with an increase in intensity in dipalmitoylphosphotidylcholine vesicles, suggesting that the peptide might associate to form higher order aggregates in lipid medium . The assignment of backbone and side-chain proton resonances has been accomplished by the combined analysis of 2D total correlated and nuclear Overhauser effect spectroscopy . The temperature dependence of amide NH chemical shifts and (1)H-(2)H exchange effect on amide NH resonances indicate the involvement of amide NH groups of Cys3, Ile5, Ile8, Val10, and Arg12 in intramolecular hydrogen bonding . The coupling constant (J(NH-C(alpha)H)) values, the set of medium-, short-, and long-range nuclear Overhauser effects, and the results of restrained structure calculation using the distance geometry algorithm for nmr applications provide evidence for a folded, loop-like structure with a type I (III) beta-turn involving Ile5, Val6, Val7, and Ile8, and two antiparallel beta-strands involving the N-terminal Arg1, Leu2, Cys3, and Val4 and the C-terminal Arg9, Val10, Cys11, and Arg12 residues . The structure of the dodecapeptide mimics the amphiphilic structure of large 30-35 residue defensins and the peptide appears to exhibit similar antimicrobial potency .

Hua Xi Yi Ke Da Xue Xue Bao, 1998 Jun, 29(2), 147 - 50
{Effects of surface roughness of two restorative materials on early Streptococcus sanguis adhesion in vitro}; Gao N et al.; This was an in vitro study aimed at the surface roughness of two kinds of commonly used restorative materials resin and alloy necessary to affect the adhesive behavior of Streptococcus sanguis(S . s) on them after 24 h . The surface roughness(SR) of each tested sample was evaluated with a profilometer quantitatively and observed with scanning electron microscope (SEM) morphologically . Then the adhesive microbial amount was determined by the clone forming unit counting method, and adhesion morphology was analyzed with SEM . The result showed a positive linear relation between the adhesion amount of S . s and the SR . The relative coefficients were rresin = 0.46(P < 0.01) and ralloy = 0.25(P < 0.01) respectively . These suggest the SR of the restorative material is important for the early adhesion of oral microbes in vitro . Therefore, before the prothesis is inserted in the patient's oral cavity, its surface should be polished as smoothly as possible so that the bacterial adhesive amount on its surface can be decreased, and hence the patient may keep in good oral health and have a prolonged use of the prothesis.

Hua Xi Yi Ke Da Xue Xue Bao, 1997 Dec, 28(4), 353 - 6
{The immune response in rats immunized systemically by the surface protein antigen P1 from streptococcus mutans conjugated with procholeragenoid}; Luo Z et al.; This study was carried out to observe the antibody responses in rats after they were immunized with the surface protein P1 of streptococcus mutans when a special adjuvant was used . Antigen P1 was conjugated covalently with procholeragenoid (PCG), and then Sprague Dawley rats were immunized with P1 or the conjugated antigen P1-PCG subcutaneously or intragastrically . Anti-P1 antibody level was assayed at different time points by ELISA . The results showed that the levels of anti-P1 SIgA antibody in saliva rose when P1-PCG was given subcutaneously or intragastrically; the antibody level following the subcutaneous injection was higher and lasted longer, compared with that following the intragastric administretion . The level of anti-P1 IgG antibody in serum only rose when the rats were immunized subcutaneously . These results implied that mucosal immune response or humoral immune response could be induced subcutaneously when PCG was used as an adjuvant.

Schweiz Med Wochenschr, 2000 Jan 22, 130(3), 72 - 6
{Spontaneous bacterial peritonitis with Streptococcus constellatus in an HIV positive patient}; Bielecki JW et al.; Liver diseases are an important cause of high morbidity and mortality in HIV-infected patients, and liver cirrhosis is the commonest cause of ascites in this population . We describe the case of a 38-year-old HIV-positive male (CDC stage B3, CD4 cell count 199/mm3) with a history of hepatitis C-associated liver cirrhosis . Following pneumonia he developed spontaneous bacterial peritonitis due to Streptococcus constellatus . Clinically noticeable was the gradually worsening course with few symptoms, despite the initially high ascitic fluid leucocyte count of over 11,000/microliter, but a favourable response to betalactam antibiotics.

Proc Natl Acad Sci U S A, 2000 Feb 29, 97(5), 2235 - 40
Crystal structure of the zymogen form of the group A Streptococcus virulence factor SpeB: an integrin-binding cysteine protease; Kagawa TF et al.; Pathogenic bacteria secrete protein toxins that weaken or disable their host, and thereby act as virulence factors . We have determined the crystal structure of streptococcal pyrogenic exotoxin B (SpeB), a cysteine protease that is a major virulence factor of the human pathogen Streptococcus pyogenes and participates in invasive disease episodes, including necrotizing fasciitis . The structure, determined for the 40-kDa precursor form of SpeB at 1.6-A resolution, reveals that the protein is a distant homologue of the papain superfamily that includes the mammalian cathepsins B, K, L, and S . Despite negligible sequence identity, the protease portion has the canonical papain fold, albeit with major loop insertions and deletions . The catalytic site differs from most other cysteine proteases in that it lacks the Asn residue of the Cys-His-Asn triad . The prosegment has a unique fold and inactivation mechanism that involves displacement of the catalytically essential His residue by a loop inserted into the active site . The structure also reveals the surface location of an integrin-binding Arg-Gly-Asp (RGD) motif that is a feature unique to SpeB among cysteine proteases and is linked to the pathogenesis of the most invasive strains of S . pyogenes.

Scand J Infect Dis, 1999, 31(6), 598 - 600
Streptococcus equinus endocarditis in a patient with pulmonary histiocytosis X; Sechi LA et al.; Although Streptococcus equinus has been isolated from the human bowel in an appreciable percentage of the adult general population, it has only rarely been described as a human pathogen . Our report describes the occurrence of S . equinus endocarditis in a patient who had no history of pre-existing heart disease, but who showed evidence of a late-stage pulmonary histiocytosis X . Endocarditis resolved promptly after antibiotic treatment, but required aortic valve substitution . Abnormalities of the immune system that have been demonstrated in patients with histiocytosis X could explain the occurrence of endocarditis in this patient.

Scand J Infect Dis, 1999, 31(6), 597 - 8
Endocarditis caused by drug-resistant Streptococcus pneumoniae in a child; Pancharoen C et al.; We report a case of infective endocarditis caused by drug-resistant Streptococcus pneumoniae . Cefazolin or cefotaxime therapy induced a partial response . Treatment with vancomycin was successful . This microorganism may be more significant in endocarditis in areas with a high prevalence of drug-resistant Streptococcus pneumoniae.

Indian J Med Res, 1999 Nov, 110, 164 - 8
Changing trend in susceptibility pattern of Streptococcus pneumoniae to penicillin in India; Lalitha MK et al.; Prior to 1995 all strains of Streptococcus pneumoniae isolated at a tertiary care hospital in south India were uniformly susceptible to penicillin . However, since late 1995 strains of S . pneumoniae with intermediate resistance to penicillin have been observed . Altogether there were 25 such isolates, 9 from invasive (5 from CSF as well as blood, 1 from pleural fluid and 3 from CSF alone) and 16 from noninvasive sites (6 from throat, 6 from sputum, 3 from eye and 1 from ear) respectively, thus 4.6 per cent of S . pneumoniae showed intermediate resistance of a total of 535 strains studied so far . The minimum inhibitory concentration (MIC) values of penicillin, erythromycin, chloramphenicol and cefotaxime were determined by agar dilution method and for confirmation, E test was carried out for penicillin alone . The MIC range obtained for penicillin was between 0.125-1.0 microgram/ml . Kirby-Bauer disc diffusion method was adopted for testing of erythromycin, chloramphenicol, co-trimoxazole, cefotaxime, tetracycline and vancomycin . We observed that none of the strains with intermediate resistance to penicillin were multidrug resistant . These strains belonged predominantly to serotype 14 (n = 10), 7B (n = 9), 19A (n = 3), 7F (n = 2) and 23F (n = 1) . Clonality was not observed in the 5 representative strains subjected to Box A finger printing method.

Antimicrob Agents Chemother, 2000 Mar, 44(3), 798 - 801
A convenient assay for estimating the possible involvement of efflux of fluoroquinolones by Streptococcus pneumoniae and Staphylococcus aureus: evidence for diminished moxifloxacin, sparfloxacin, and trovafloxacin efflux; Beyer R et al.; We developed a simplified assay for estimating efflux by measuring the effect of reserpine on the growth of Streptococcus pneumoniae and Staphylococcus aureus over 7 h . Reserpine enhanced ciprofloxacin and levofloxacin 17 to 68% . The hydrophobic drug trovafloxacin and the drug moxifloxacin, with a bulky C-7 substituent but hydrophilicity similar to that of levofloxacin, showed little (0 to 11%) reserpine-enhancing effect . The ease of resistant mutant strain selection correlated with efflux susceptibility.

Antimicrob Agents Chemother, 2000 Mar, 44(3), 790 - 3
Characterization of the Tn916-like transposon Tn3872 in a strain of abiotrophia defectiva (Streptococcus defectivus) causing sequential episodes of endocarditis in a child; Poyart C et al.; Clinical blood isolates from three sequential episodes of endocarditis occurring over a 6-month period in a child with a malformative cardiopathy were investigated . All isolates identified as Abiotrophia defectiva were resistant to erythromycin-clindamycin and to tetracycline-minocycline, due to the presence of sequences homologous to the erythromycin resistance gene ermB and to the tetracycline resistance gene tet(M), respectively . These resistance genes were located on a chromosomally borne composite Tn916-related transposon . These results demonstrate the involvement of conjugative transposons in the dissemination of antibiotic resistance in the genus Abiotrophia.

Antimicrob Agents Chemother, 2000 Mar, 44(3), 787 - 9
Streptococcus gordonii strains resistant to fluorodeoxyuridine contain mutations in the thymidine kinase gene and are deficient in thymidine kinase activity; Franke CA et al.; Mutants of Streptococcus gordonii resistant to 5-fluorodeoxyuridine (FUdR(r)) were isolated . Each strain contained a point mutation resulting in the premature termination of the thymidine kinase (TK) open reading frame (tdk) . In vitro translation of the mutant tdk coding regions resulted in synthesis of truncated TK polypeptides deficient in TK activity.

Antimicrob Agents Chemother, 2000 Mar, 44(3), 773 - 4
Comparative activities of ciprofloxacin and levofloxacin against Streptococcus pneumoniae in an In vitro dynamic model; Zinner SH et al.; The activities of levofloxacin (500 mg every 24 h) and ciprofloxacin (750 mg every 12 h) against six pneumococcal isolates in an in vitro dynamic model were compared . For one strain, levofloxacin reduced the inoculum by over 4 log CFU/ml and ciprofloxacin reduced the inoculum by over 2 log CFU/ml . For four isolates, both drugs reduced inocula by 4 log CFU/ml within 6 h, suggesting that this dose of ciprofloxacin should be as effective as levofloxacin against these pneumococci.

Antimicrob Agents Chemother, 2000 Mar, 44(3), 767 - 70
Gemifloxacin is effective in experimental pneumococcal meningitis; Smirnov A et al.; In a rabbit model of Streptococcus pneumoniae meningitis, 5 mg of gemifloxacin mesylate (SB-265805) per kg/h reduced the bacterial titers in cerebrospinal fluid (CSF) almost as rapidly as 10 mg of ceftriaxone per kg/h (Deltalog CFU/ml/h +/- standard deviation {SD}, -0.25 +/- 0.09 versus -0.38 +/- 0.11; serum and CSF concentrations of gemifloxacin were 2.1 +/- 1.4 mg/liter and 0.59 +/- 0.38 mg/liter, respectively, at 24 h) . Coadministration of 1 mg of dexamethasone per kg did not affect gemifloxacin serum and CSF levels (2.7 +/- 1.4 mg/liter and 0.75 +/- 0.34 mg/liter, respectively, at 24 h) or activity (Deltalog CFU/ml/h +/- SD, -0.26 +/- 0.11).

Antimicrob Agents Chemother, 2000 Mar, 44(3), 732 - 8
Mutations in ribosomal protein L16 conferring reduced susceptibility to evernimicin (SCH27899): implications for mechanism of action; Adrian PV et al.; A clinical isolate of Streptococcus pneumoniae (SP#5) that showed decreased susceptibility to evernimicin (MIC, 1.5 microgram/ml) was investigated . A 4,255-bp EcoRI fragment cloned from SP#5 was identified by its ability to transform evernimicin-susceptible S . pneumoniae R6 (MIC, 0.03 microgram/ml) such that the evernimicin MIC was 1.5 microgram/ml . Nucleotide sequence analysis of this fragment revealed that it contained portions of the S10-spc ribosomal protein operons . The nucleotide sequences of resistant and susceptible isolates were compared, and a point mutation (thymine to guanine) that causes an Ile52-Ser substitution in ribosomal protein L16 was identified . The role of this mutation in decreasing susceptibility to evernimicin was confirmed by direct transformation of the altered L16 gene . The presence of the L16 mutation in the resistant strain suggests that evernimicin is an inhibitor of protein synthesis . This was confirmed by inhibition studies using radiolabeled substrates, which showed that the addition of evernimicin at sub-MIC levels resulted in a rapid decrease in the incorporation of radiolabeled isoleucine in a susceptible isolate (SP#3) but was much less effective against SP#5 . The incorporation of isoleucine showed a linear response to the dose level of evernimicin . The incorporation of other classes of labeled substrates was unaffected or much delayed, indicating that these were secondary effects.

Antimicrob Agents Chemother, 2000 Mar, 44(3), 598 - 601
Activities of trovafloxacin, gatifloxacin, clinafloxacin, sparfloxacin, levofloxacin, and ciprofloxacin against penicillin-resistant Streptococcus pneumoniae in an in vitro infection model; Hershberger E et al.; We adapted an in vitro pharmacodynamic model of infection to incorporate infected fibrin clots . The bactericidal activities of various fluoroquinolones against two strains of penicillin-resistant Streptococcus pneumoniae were studied over a 48-h period . Bacteria were prepared in Muller-Hinton broth by using colonies from a 24-h tryptic soy agar plus 5% sheep blood plate and were added to a mixture of cryoprecipitate (80%) and thrombin (10%) to achieve approximately 10(6) CFU of organism per fibrin clot . The fibrin clots were suspended into the models and removed, in triplicate, at various time points over 48 h . Control models were also conducted to characterize the growth of S . pneumoniae in the growth medium without antibiotic . Trovafloxacin, gatifloxacin, clinafloxacin, sparfloxacin, levofloxacin, and ciprofloxacin were administered to simulate their pharmacokinetic profiles in humans . Fibrin clot samples were also plated onto antibiotic-containing tryptic soy agar plus 5% lysed horse blood to detect resistance . The newer fluoroquinolones demonstrated better activity than ciprofloxacin against both isolates . In conclusion, the newer quinolones demonstrated significant activity against penicillin-resistant S . pneumoniae, with standard dosing resulting in area under the concentration-time curve/MIC ratios and peak concentration/MIC ratios that resulted in 99.9% killing against these isolates.

Antimicrob Agents Chemother, 2000 Mar, 44(3), 484 - 8
Nasal carriage in Vietnamese children of Streptococcus pneumoniae resistant to multiple antimicrobial agents; Parry CM et al.; Resistance to antimicrobial agents in Streptococcus pneumoniae is increasing rapidly in many Asian countries . There is little recent information concerning resistance levels in Vietnam . A prospective study of pneumococcal carriage in 911 urban and rural Vietnamese children, of whom 44% were nasal carriers, was performed . Carriage was more common in children <5 years old than in those >/=5 years old (192 of 389 {49.4%} versus 212 of 522 {40.6%}; P, 0.01) . A total of 136 of 399 isolates (34%) had intermediate susceptibility to penicillin (MIC, 0.1 to 1 mg/liter), and 76 of 399 isolates (19%) showed resistance (MIC, >1.0 mg/liter) . A total of 54 of 399 isolates (13%) had intermediate susceptibility to ceftriaxone, and 3 of 399 isolates (1%) were resistant . Penicillin resistance was 21.7 (95% confidence interval, 7.0 to 67.6) times more common in urban than in rural children (35 versus 2%; P, <0.001) . More than 40% of isolates from urban children were also resistant to erythromycin, trimethoprim-sulfamethoxazole, chloramphenicol, and tetracycline . Penicillin resistance was independently associated with an urban location when the age of the child was controlled for . Multidrug resistance (resistance to three or more antimicrobial agent groups) was present in 32% of isolates overall but in 39% of isolates with intermediate susceptibility to penicillin and 86% of isolates with penicillin resistance . The predominant serotypes of the S . pneumoniae isolates were 19, 23, 14, 6, and 18 . Almost half of the penicillin-resistant isolates serotyped were serotype 23, and these isolates were often multidrug resistant . This study suggests that resistance to penicillin and other antimicrobial agents is common in carriage isolates of S . pneumoniae from children in Vietnam.

J Okla State Med Assoc, 2000 Jan, 93(1), 25 - 8
Severe invasive group A beta-hemolytic streptococcus infection complicating pharyngitis: a case report and discussion; Kelly SB et al.; Group A beta-hemolytic streptococcus (GABHS) has long been recognized as a deadly pathogen with manifestations ranging from impetigo to necrotizing fasciitis . Bacteremia from streptococcal pharyngitis is a rare complication . We report a patient presenting with septic shock and diabetic ketoacidosis from streptococcal pharyngitis . The pathophysiology, classification, and treatment of invasive group A streptococcal infection is discussed.

Zentralbl Veterinarmed B, 1999 Dec, 46(10), 723 - 9
Isolation and further characterization of phase variants of Streptococcus equi subsp . zooepidemicus; Abdulmawjood A et al.; In the present study the soft agar technique was used to isolate phase variants of S . equi subsp . zooepidemicus-cultures isolated from infections of horses . The phase variants were characterized by a compact or diffuse colony morphology in this media . The variants could be cultivated separately and further characterized genotypically by RAPD analysis and by macrorestriction analysis of their chromosomal DNA by pulsed-field gel electrophoresis, indicating the identity of both strains of each pair . The diffuse colony variants grew uniformly turbid after cultivation in fluid media, did not haemagglutinate rabbit erythrocytes, and displayed a reduced surface hydrophobicity in hexadecane and phenyl-sepharose adherence tests . The compact colony variants generally grew as sediment with clear supernatant in fluid media, haemagglutinated rabbit erythrocytes and showed an enhanced surface hydrophobicity in both hydrophobicity tests . The presented soft agar technique allowed a demonstration of phase variation of S . equi subsp . zooepidemicus and a subsequent isolation of the variants . This might be an important prerequisite to understanding the pathogenic importance of phase variation among isolates of this bacterial species.

Biochim Biophys Acta, 2000 Feb 15, 1463(2), 307 - 22
Cardiolipin, alpha-D-glucopyranosyl, and L-lysylcardiolipin from gram-positive bacteria: FAB MS, monofilm and X-ray powder diffraction studies; Gutberlet T et al.; Cardiolipin preparations from Streptococcus B, Listeria welshimeri, Staphylococcus aureus, and a glucosyl and lysyl derivative of cardiolipin were analysed for fatty acid composition and fatty acid combinations . Three different fatty acid patterns are described and up to 17 molecular species were identified in Streptococcus B lipids by high resolution FAB MS . The physicochemical properties of these lipids were characterised in the sodium salt form by monofilm experiments and X-ray powder diffraction . All lipids formed stable monofilms . The minimal space requirement of unsubstituted cardiolipin was dictated by the fatty acid pattern . Substitution with L-lysine led to a decrease of the molecular area, substitution with D-glucopyranosyl to an increase . On self assembly at 100% relative humidity, all preparations adopted lamellar structures . They showed a high degree of order, in spite of the heterogeneous fatty acid compositions and numerous fatty acid combinations . The repeat distances in lamellar fluid phase varied between 4.99 and 5 . 52 nm, the bilayer thickness between 3.70 and 4.46 nm . Surprising were the low values of sorbed water per molecule of the glucosyl and lysyl derivatives which were 58 and 60%, compared with those of the respective cardiolipin . When Na(+) was replaced as counterion by Ba(2+), the bilayer structure was retained, but the lipids were in the lamellar gel phase and the fatty acids were tilted between 32 and 53 degrees away from the bilayer normal . Wide angle X-ray diffraction studies and electron density profiles are also reported . Particular properties of glucosyl cardiolipin are discussed.

J Clin Periodontol, 2000 Jan, 27(1), 30 - 6
The effect of scaling and root planing on the clinical and microbiological parameters of periodontal diseases: 12-month results; Cugini MA et al.; BACKGROUND/AIMS: Previously, we reported that SRP resulted in a decrease in mean pocket depth and attachment level and reduced prevalence and levels of Bacteroidesforsythus, Porphyromonas gingivalis, and Treponema denticola at 3 and 6 months post-SRP in 57 subjects with adult periodontitis . 32 of the 57 subjects were monitored at 9 and 12 months . Thus, the purpose of the present investigation was to evaluate the microbial and clinical effects of SRP in 32 (mean age 48+/-11) subjects over a 12-month period . METHOD: Clinical assessments of plaque, gingival redness, suppuration, bleeding on probing, pocket depth and attachment level were made prior to SRP and at 3, 6, 9, and 12 months post-therapy . Subgingival plaque samples were taken at each visit and analyzed using the checkerboard DNA-DNA hybridization technique for the presence and levels of 40 subgingival species . Each subject also received maintenance scaling at each of the subsequent monitoring visits . Differences in clinical parameters and prevalence and levels of bacterial species were analyzed pre- and post-therapy using the Wilcoxon signed ranks test . The Quade test for related samples was used for analysis of multiple visits . RESULTS: Mean pocket depth (mm+/-SEM) decreased from 3.2+/-0.3 at baseline to 2.9+/-0.3 at 12 months (p<0.01) . Mean attachment level showed significant reduction at 6 months, but did not diminish further . Bleeding on probing and plaque were significantly reduced at 12 months (p<0.001, p<0.05, respectively) . P . gingivalis, B . forsythus and T . denticola decreased in prevalence and levels up to the 6-month visit and remained at these lower levels at 9 and 12 months . Significant increases in levels and prevalence were noted at 12 months for Actinomyces naeslundii genospecies 2, Actinomyces odontolyticus, Fusobacterium nucleatum ss polymorphum, Streptococcus mitis, Capnocytophaga sp, and Veillonella parvula . CONCLUSIONS: The data suggest that the maintenance phase of therapy may be essential in consolidating clinical and microbiological improvements achieved as a result of initial therapy.

Oral Dis, 2000 Jan, 6(1), 12 - 4
Influence of (S)-ketoprofen and fluoride on caries in rats; Bowen WH et al.; OBJECTIVE: Non-steroidal anti-inflammatory agents (e.g., ketoprofen) used topically appear to be effective in reducing bone loss in the ligature model of periodontitis . Ketoprofen, in common with some food preservatives, e.g., benzoate and sorbate, is a weak acid . Fluoride, too, may behave as a weak acid and, similar to the other agents, may exert antibacterial effects . The purpose of the present study was to determine whether a combination of (S)-ketoprofen, an enantiomer of ketoprofen, alone or in combination with fluoride, would suppress Streptococcus sobrinus populations and reduce the incidence of dental caries in rats . MATERIALS AND METHODS: Toothpastes containing ketoprofen and/or monofluorophosphate were applied to the teeth of six groups of 20 rats twice daily for 5 weeks . RESULTS: Fewest S . sobrinus were found in the group treated with a paste containing 3% (S)-ketoprofen + 0.1% F . This group also displayed the lowest incidence of smooth surface caries of all groups . Severity of sulcal surface caries was also lowest in this group . CONCLUSIONS: Results from this study show that the (S) enantiomer of ketoprofen enhances the caries protective effect of fluoride . It is conceivable that this combination could be effective in combating the two most common maladies of the mouth; periodontal disease and dental caries.

Mol Microbiol, 2000 Feb, 35(3), 566 - 76
A genomic analysis of two-component signal transduction in Streptococcus pneumoniae; Throup JP et al.; A genomics-based approach was used to identify the entire gene complement of putative two-component signal transduction systems (TCSTSs) in Streptococcus pneumoniae . A total of 14 open reading frames (ORFs) were identified as putative response regulators, 13 of which were adjacent to genes encoding probable histidine kinases . Both the histidine kinase and response regulator proteins were categorized into subfamilies on the basis of phylogeny . Through a systematic programme of mutagenesis, the importance of each novel TCSTS was determined with respect to viability and pathogenicity . One TCSTS was identified that was essential for the growth of S . pneumoniaeThis locus was highly homologous to the yycFG gene pair encoding the essential response regulator/histidine kinase proteins identified in Bacillus subtilis and Staphylococcus aureus . Separate deletions of eight other loci led in each case to a dramatic attenuation of growth in a mouse respiratory tract infection model, suggesting that these signal transduction systems are important for the in vivo adaptation and pathogenesis of S . pneumoniae . The identification of conserved TCSTSs important for both pathogenicity and viability in a Gram-positive pathogen highlights the potential of two-component signal transduction as a multicomponent target for antibacterial drug discovery.

Clin Exp Dermatol, 2000 Jan, 25(1), 57 - 61
Bacterial superantigens and inflammatory skin diseases; Skov L et al.; Bacteria seem to play an important role in the induction and maintenance of inflammatory skin diseases such as psoriasis and atopic dermatitis . Toxins from bacteria including Streptococcus and Staphylococcus aureus, have been shown to function as a new type of allergen termed 'superantigen' . Superantigens bypass the normal control of T-cell activation and activate all T-cell clones bearing certain types of variable chain on the T-cell receptor: this leads to vigorous T-cell activation and cytokine release . These bacterial superantigens may be involved in induction and aggravation of inflammatory skin diseases . Guttate psoriasis is often preceded by a streptococcal throat infection and T cells specific for streptococcal superantigens have been identified in the skin of patients . The skin of patients with atopic dermatitis is often colonized with superantigen-releasing Staph . aureus, and application of a staphylococcal superantigen to human skin induces an eczematoid reaction.

Chemotherapy, 2000 Mar-Apr, 46(2), 95 - 9
In vitro and in vivo antibacterial activities of biapenem in the fields of obstetrics and gynecology; Mikamo H et al.; Biapenem is a new injectable carbapenem antibiotic which has favorable pharmacokinetic properties, and is stable to hydrolysis by dehydropeptidase I . Biapenem inhibited more than 90% of clinical isolates of Streptococcus agalactiae, Escherichia coli, Peptostreptococcus magnus, Bacteroides fragilis and Prevotella bivia at the concentration of 3.13 mg/l . The MIC(90) of biapenem against Pseudomonas aeruginosa was lower than that of panipenem, equivalent to that of imipenem, and greater than that of meropenem . The in vivo efficacy of biapenem was evaluated using the experimental infection model of uterine endometritis . The accumulation of neutrophils in the uterus in the biapenem- treated group was less marked than in the nontreated group, as well as bacteriological response . These results suggest that the new antimicrobial agent biapenem might be useful for the treatment of polymicrobial infections in the fields of obstetrics and gynecology .

Am J Psychiatry, 2000 Feb, 157(2), 281 - 3
MRI assessment of children with obsessive-compulsive disorder or tics associated with streptococcal infection; Giedd JN et al.; OBJECTIVE: The authors assessed selective basal ganglia involvement in a subgroup of children with obsessive-compulsive disorder (OCD) and/or tics believed to be associated with streptococcal infection . METHOD: Using computer-assisted morphometric techniques, they analyzed the cerebral magnetic resonance images of 34 children with presumed streptococcus-associated OCD and/or tics and 82 healthy comparison children who were matched for age and sex . RESULTS: The average sizes of the caudate, putamen, and globus pallidus, but not of the thalamus or total cerebrum, were significantly greater in the group of children with streptococcus-associated OCD and/or tics than in the healthy children . The differences were similar to those found previously for subjects with Sydenham's chorea compared with normal subjects . CONCLUSIONS: These results support the hypothesis that there is a distinct subgroup of subjects with OCD and/or tics who have enlarged basal ganglia . These findings are consistent with the hypothesis of an autoimmune response to streptococcal infection.

Clin Infect Dis, 2000 Feb, 30(2), 319 - 21
An outbreak of Streptococcus pneumoniae serotype 1 in a closed community in southern Israel; Dagan R et al.; An outbreak of Streptococcus pneumoniae serotype 1 occurred in a closed community that was characterized by poverty and crowding . Vaccine was administered to individuals aged >2 years; no new cases occurred among vaccine recipients . Six weeks after vaccination, carriage of serotype 1, but not of other serotypes, decreased 8.8-fold . This suggests that the reduction in serotype 1 carriage reflects the natural course of the outbreak rather than a vaccine effect . Polysaccharide vaccine may be helpful in terminating pneumococcal outbreaks but may not affect pneumococcal carriage.

Clin Infect Dis, 2000 Feb, 30(2), 282 - 7
A 5-year review of recurrent group B streptococcal disease: lessons from twin infants; Moylett EH et al.; Recurrent invasive disease due to group B Streptococcus (GBS) in twin infants has not been reported . We report 2 cases of recurrent GBS afflicting both siblings of a set of dichorionic twin infants . The maternal and infant colonizing and invasive strains were identical by serotyping and pulsed-field gel electrophoresis (PFGE) . Despite attempts at eradication with different antibiotic regimens, the infants remained colonized after treatment of the second episode . A 5-year review of recurrent invasive GBS disease in infants in our affiliated hospitals was undertaken, and 6 further cases were identified . Serotyping and PFGE of isolates from initial and second episodes were genotypically identical for each case . Three infants each had GBS serotype Ia or V disease and 2 had GBS serotype III disease . The exact pathogenesis of recurrent GBS disease remains unclear, but our data support the hypothesis that persistent mucosal colonization with the original GBS strain rather than new acquisition is a pivotal factor in disease recurrence.

Clin Infect Dis, 2000 Feb, 30(2), 276 - 81
Invasive disease due to group B Streptococcus in pregnant women and neonates from diverse population groups; Zaleznik DF et al.; From 1993 through 1996, surveillance for invasive disease due to group B Streptococcus (GBS) in neonates aged <7 days and in peripartum pregnant women was performed in a racially and ethnically diverse cohort in 4 cities in the United States . In a birth population of 157,184, 130 neonatal cases (0.8 per 1000) and 54 maternal cases (0.3 per 1000) were identified . Significant correlates with neonatal disease were black or Hispanic race and a birth weight <2500 g . The attack rate for peripartum maternal infection varied widely by city and may have been influenced by the frequency of administration of intrapartum antibiotics or of evaluating febrile women by performance of blood cultures . Pregnancy loss or GBS disease in the infant occurred in 28% of these maternal cases . Among neonatal and maternal GBS isolates, serotypes Ia (34%-37%) and III (25%-26%) predominated, and type V was frequent (14%-23%) . These results provide a description of invasive GBS perinatal infection during the period in which guidelines for prevention were actively disseminated.

Ann Otolaryngol Chir Cervicofac, 2000 Feb, 117(1), 19 - 25
{Orbital complications of sinusitis in adults}; Barry B et al.; Orbital complications of sinusitis are rare in adults but delayed diagnosis is vision and life threatening . We report our experience in 6 patients to present clinical history, bacteriology and discuss the modality of treatment . There were 4 young men and 2 women, aged from 16 to 79 years old . Only one patient had an immunocompromised underlying condition (HIV infection) . Four patients had preseptal abscesses and three post septal cellulitis or abscess (one patient had preseptal abscess and post septal abscess and hematoma) . Two patients had a complete unilateral loss of light perception . Pathogens encountered were Streptococcus species: 4, strict anaerobes: 1, Pseudomonas aeruginosa: 1 (patient with AIDS) . Patients recovered from infection with antibiotics in 6 and surgery in 5 but sequellar blindness occurred in 2 patients . Our experience emphasizes the necessity of antibiotic treatment in bacterial sinusitis and importance of early diagnosis and appropriate management of complications.

Chest, 2000 Feb, 117(2), 530 - 41
The drug-resistant pneumococcus: clinical relevance, therapy, and prevention; Harwell JI et al.; Streptococcus pneumoniae has been known for > 100 years as the most important bacterial pathogen of the respiratory tract in adults and children . In recent years, the pneumococcus has begun to exhibit increasing resistance to antimicrobial agents . Because of the huge number of infections caused by this organism, the development of resistance has changed the approach to many infectious disease problems, particularly with regard to empiric antibiotic therapy and prophylaxis . In our review of the antibiotic-resistant pneumococcus, we review the microbiologic basis for resistance, risk factors for and clinical relevance of infection by a resistant organism, and infection control measures.

J Infect Dis, 2000 Feb, 181(2), 653 - 8
Maternal antibody transfer in baboons and mice vaccinated with a group B streptococcal polysaccharide conjugate; Paoletti LC et al.; Two animal models were used to study maternal transfer of antibody to a group B Streptococcus (GBS) type III polysaccharide-tetanus toxoid (III-TT) conjugate . The III-TT vaccine protected all 27 mouse pups born to vaccinated dams against a GBS challenge . In a separate study of vaccinated mouse dams and pups, maternal sera contained all 4 subclasses of polysaccharide-specific IgG, with IgG1 accounting for 83% of total IgG . Specific IgG subclass distribution (IgG1>>IgG2a=IgG2b=IgG3) in newborn pups closely resembled that in their mothers . Seven of 9 female baboons given the III-TT vaccine had 5- to 36-fold increases in specific antibody from baseline levels; they transferred 26%-185% of specific antibody to their offspring . Matched maternal and neonatal sera obtained at delivery were functionally equivalent in an in vitro opsonophagocytosis assay . These preclinical studies provide further evidence for effective immunogenicity of GBS conjugate vaccine and efficient transport of functionally active maternal antibody.

Am J Public Health, 2000 Feb, 90(2), 223 - 9
Mortality from invasive pneumococcal pneumonia in the era of antibiotic resistance, 1995-1997; Feikin DR et al.; OBJECTIVES: This study examined epidemiologic factors affecting mortality from pneumococcal pneumonia in 1995 through 1997 . METHODS: Persons residing in a surveillance area who had community-acquired pneumonia requiring hospitalization and Streptococcus pneumoniae isolated from a sterile site were included in the analysis . Factors affecting mortality were evaluated in univariate and multivariate analyses . The number of deaths from pneumococcal pneumonia requiring hospitalization in the United States in 1996 was estimated . RESULTS: Of 5837 cases, 12% were fatal . Increased mortality was associated with older age, underlying disease . Asian race, and residence in Toronto/Peel, Ontario . When these factors were controlled for, increased mortality was not associated with resistance to penicillin or cefotaxime . However, when deaths during the first 4 hospital days were excluded, mortality was significantly associated with penicillin minimum inhibitory concentrations of 4.0 or higher and cefotaxime minimum inhibitory concentrations of 2.0 or higher . In 1996, about 7000 to 12,500 deaths occurred in the United States from pneumococcal pneumonia requiring hospitalization . CONCLUSIONS: Older age and underlying disease remain the most important factors influencing death from pneumococcal pneumonia . Mortality was not elevated in most infections with beta-lactam-resistant pneumococci.

J Dent, 2000 Jan, 28(1), 45 - 50
Composition of the oral streptococcal flora in healthy children; Lucas VS et al.; OBJECTIVES: To identify the predominant streptococcal species in the mouths of healthy children and to investigate the composition of the oral streptococcal flora over a period of 4 months . PATIENTS AND METHODS: The subjects were 33 fit, healthy schoolchildren aged between 5 and 16 years . These children were part of a large study and were the matched controls for a group of subjects undergoing bone marrow transplantation . The oral flora was sampled using an oral rinse technique on two separate occasions 4 months apart . The outcome measures were the number of each streptococcal species per millilitre of oral rinse; the isolation frequency of each species; the proportion of each species as a percentage of both the total streptococcal count and the total anaerobic count . RESULTS: The predominant species were Streptococcus salivarius, S . oralis and S . mitis . There was no significant variation in the composition of the oral streptococcal flora over the 4 month period . CONCLUSIONS: The oral rinse technique provides a reliable method of sampling the streptococcal flora of children.

Acta Crystallogr D Biol Crystallogr, 1999 Dec, 55 ( Pt 12), 2041 - 2
Crystallization and preliminary X-ray diffraction studies of Streptococcus pyogenes plasmid pSM19035-encoded omega transcriptional repressor; Murayama K et al.; The transcriptional repressor, omega protein, from the Streptococcus pyogenes broad-host-range plasmid pSM19035 was crystallized at pH 7 . 5 and 8.5 by the vapour-diffusion method using PEG 4000 as precipitant . Two crystal forms were obtained; the first belongs to the tetragonal space group P4(1)2(1)2 or P4(3)2(1)2 and the second to the hexagonal space group P6(1) or P6(5) . The crystals are most likely to contain one omega protein in the asymmetric unit, with V(m) values of 3.2 and 3.5 A(3) Da(-1), respectively . The crystals diffract X-rays to 2.4 and 2.9 A resolution for the tetragonal and hexagonal systems, -respectively.

Lancet, 2000 Jan 29, 355(9201), 369 - 73
Clinical presentation and outcome of Pneumocystis carinii pneumonia in Malawian children; Graham SM et al.; BACKGROUND: Necropsy studies from Africa have shown that Pneumocystis carinii pneumonia (PCP) is common in infants with HIV infection . We aimed to describe the rate, clinical presentation, and outcome of PCP in young Malawian children with acute severe pneumonia . METHODS: Children aged between 2 months and 5 years who were in hospital with a diagnosis of severe pneumonia were admitted to a study ward for clinical monitoring . We carried out blood culture, immunofluorescence on nasopharyngeal aspirate samples to test for PCP, polymerase chain reaction to detect HIV, and chest radiography . FINDINGS: 16 cases of PCP were identified among 150 children with radiologically confirmed severe pneumonia . All were HIV-positive and younger than 6 months . 21 children had bacterial pneumonia (including one who was also PCP positive) and 114 were not confirmed . The most common bacterial pathogens among children without PCP were Streptococcus pneumoniae (eight) and non-typhoidal salmonellae (seven) . On admission, children with confirmed PCP had a lower mean age, body temperature, and oxygen saturation than children with bacterial pneumonia and were less likely to have a focal abnormality on auscultation . Oxygen requirements were much greater in children with PCP than those with bacterial pneumonias (96 of 105 hospital days vs 15 of 94, p<0.0001) . Ten of 16 children with PCP and six of 21 with bacterial pneumonia died (relative risk 2.19 {95% CI 1.0-4.7}) . The overall case-fatality rate of severe pneumonia was 22% . In addition to a strong association with PCP, a fatal outcome was significantly and independently associated with HIV infection (2.98 {1.1-7.9}) and with age under 6 months (2.76 {1.0-5.2}) . INTERPRETATION: PCP is common and contributes to the high mortality from pneumonia in Malawian infants . Clinical features are helpful in diagnosis . The study highlights the impact of HIV infection and difficult issues of management in countries with few resources.

Vet Microbiol, 2000 Jan, 71(1-2), 103 - 11
Genomic fingerprinting of pigeon Streptococcus gallolyticus strains of different virulence by randomly amplified polymorphic DNA (RAPD) analysis; Baele M et al.; Randomly amplified polymorphic DNA (RAPD) analysis was performed on 95 pigeon S . gallolyticus strains of different virulence and belonging to different biotypes and different culture supernatant phenotypes as determined by SDS-PAGE . Four distinct RAPD patterns, designated A, B, C and D, were distinguished using primer OPM6 (5'CTGGGCAACT) . All 76 strains generating RAPD pattern A or B were designated highly virulent on the basis of their SDS-PAGE pattern . Five of seven strains generating RAPD pattern C and 11 of 12 strains generating RAPD pattern D belonged to the moderately virulent and low virulent culture supernatant phenotype groups, respectively . Only one RAPD group C strain belonged to a highly virulent culture supernatant phenotype group . There was a correlation between biotype and RAPD patterns . These findings indicate that there is a high correlation between RAPD pattern and virulence for pigeons . Therefore, RAPD typing seems a rapid, reliable method to distinguish pigeon S . gallolyticus strains of high, moderate and low virulence.

Nurse Pract, 2000 Jan, 25(1), 69, 73 - 80, 85; quiz 86-7
Acute otitis media and pneumococcal resistance: making judicious management decisions; Tigges BB; The emergence of drug-resistant Streptococcus pneumoniae (DRSP) has implications for the primary care provider who treats acute otitis media (AOM) in children . AOM must be carefully distinguished from otitis media with effusion (OME) . Antibiotic treatment for AOM is recommended because of the low rate of spontaneous resolution of S . pneumoniae infection and the risk of suppurative complications, particularly in young children . Amoxicillin continues to be the first drug of choice . Children for whom the first course of antibiotics fails should be treated with amoxicillin-clavulanate, cefuroxime axetil, or ceftriaxone . Trimethoprim-sulfamethoxazole, the macrolides, and most of the cephalosporins have limited effectiveness against DRSP and should no longer have a major role in AOM treatment . OME need not be treated with antibiotics unless the effusion has been present for 3 to 4 months . Tympanostomy tubes are an effective treatment for both chronic OME and recurrent AOM . Given the significant increase of DRSP during the past decade, clinicians must minimize antibiotic use and, when antibiotics are required, make judicious clinical decisions.

J Biol Chem, 2000 Feb 11, 275(6), 3907 - 14
Mechanism of type 3 capsular polysaccharide synthesis in Streptococcus pneumoniae; Cartee RT et al.; The glycosidic linkages of the type 3 capsular polysaccharide of Streptococcus pneumoniae ({3)-beta-D-GlcUA-(1-->4)-beta-D-Glc-(1-->}(n)) are formed by the membrane-associated type 3 synthase (Cps3S), which is capable of synthesizing polymer from UDP sugar precursors . Using membrane preparations of S . pneumoniae in an in vitro assay, we observed type 3 synthase activity in the presence of either Mn(2+) or Mg(2+) with maximal levels seen with 10-20 mM Mn(2+) . High molecular weight polymer synthesized in the assay was composed of Glc and glucuronic acid and could be degraded to a low molecular weight product by a type 3-specific depolymerase from Bacillus circulans . Additionally, the polymer bound specifically to an affinity column made with a type 3 polysaccharide-specific monoclonal antibody . The polysaccharide was rapidly synthesized from smaller chains and remained associated with the enzyme-containing membrane fraction throughout its synthesis, indicating a processive mechanism of synthesis . Release of the polysaccharide was observed, however, when the level of one of the substrates became limiting . Finally, addition of sugars to the growing type 3 polysaccharide was shown to occur at the nonreducing end of the polysaccharide chain.

J Antimicrob Chemother, 2000 Feb, 45(2), 153 - 8
The effect of triclosan toothpaste on enamel demineralization in a bacterial demineralization model; van Loveren C et al.; Triclosan has been incorporated into toothpaste to enhance inhibitory effects on bacterial metabolism in dental plaque . Many studies have confirmed these effects by showing a reduction of accumulation of dental plaque, gingivitis and calculus . However, there is no evidence for triclosan having an inhibitory effect on the dental plaque-induced demineralization of the dental hard tissues . Therefore, the effect of 0.3% triclosan added to non-fluoride and fluoride toothpaste was tested in an in vitro model, in which bovine enamel specimens were to be demineralized by acids produced in overlaying Streptococcus mutans suspensions . In a first set of experiments the toothpastes were added to the S . mutans suspensions at 1:100, 1:1000 and 1:10,000 (w/v) dilutions . After 22 h incubation at 37 degrees C the suspensions were removed and assessed for calcium and lactate content, and pH . In this set of experiments, triclosan had no additive protective effect to the non-fluoride or fluoride toothpaste . In a second set of experiments, the enamel specimens were immersed daily for 3 min in 30% (w/v) slurries of the toothpastes before the 22 h incubation with the S . mutans suspensions . Under these conditions, triclosan showed an additional protective effect compared with non-fluoride toothpaste at a low concentration of S . mutans cells (0.07 mg cells dry weight per 600 microL suspension) . It is concluded that the enamel surface may act as a reservoir for triclosan, which may protect the enamel surface against a mild acid attack . In combination with fluoride, however, as in toothpaste, triclosan has no additional protective effect against demineralization.

J Dairy Sci, 2000 Jan, 83(1), 70 - 6
Outcome of clinical mastitis in dairy heifers assessed by reexamination of cases one month after treatment; Waage S et al.; Heifers that were treated for clinical mastitis prior to parturition or within 14 d postpartum were reexamined approximately 1 mo after treatment . Clinical examination of the heifers and microbiological examination of quarter milk samples were carried out on both occasions . Of the 1000 heifers included in the study, 10.9% were culled within 28 d after treatment . Udder damage caused by mastitis was the only or main reason for culling in 96% of those heifers . In comparison, 4.5% of nonmastitic heifers from the same herds were culled within 30 d postpartum . Twenty-five percent of those heifers that were not culled at d 28 after treatment had at least one nonfunctional quarter at that time . One thousand one hundred twenty-two quarters that were clinically affected at the time of treatment were reexamined; 22% were nonfunctional, 14% were still affected by clinical mastitis, 12% had subclinical mastitis, 5% had a latent infection with coagulase-positive staphylococci or Streptococcus dysgalactiae, and 46% were bacteriologically negative and had a normal cell count at the time of reexamination . High percentages of nonfunctional quarters were observed among those quarters that were infected with Arcanobacterium pyogenes or with coagulase-positive staphylococci at treatment . When all quarters that were clinically affected at treatment were considered, 40% of quarters were cured and were still in lactation at reexamination . Quarters infected with coagulase-negative staphylococci had a higher cure rate than quarters infected with other organisms . At reexamination, clinical signs of thelitis were observed in many of those quarters that were nonfunctional following the episode of clinical mastitis and also in 25% of lactating quarters in which clinical mastitis persisted.

Microbiology, 2000 Jan, 146 ( Pt 1), 107 - 17
Multiple stress responses in Streptococcus mutans and the induction of general and stress-specific proteins; Svensater G et al.; The authors have previously demonstrated that Streptococcus mutans shows an exponential-phase acid-tolerance response following an acid shock from pH 7.5 to 5.5 that enhances survival at pH 3.0 . In this study the response of S . mutans H7 to acid shock was compared with the responses generated by salt, heat, oxidation and starvation . Prior induction of the acid-tolerance response did not cross-protect the cells from a subsequent challenge by the other stresses; however, prior adaptation to the other stresses, except heat (42 degrees C), protected the cells during a subsequent acid challenge at pH 3.5 . Starvation by fivefold dilution of the basal medium (BM) plus fivefold reduction of its glucose content increased the numbers of survivors 12-fold, whereas elimination of glucose from fivefold-diluted BM led to a sevenfold enhancement compared to the control cells; this indicated a relationship between the acid and starvation responses . The stress responses were further characterized by comparing the 2D electrophoretic protein profiles of exponential-phase cells subjected to the various stress conditions . Cells were grown to exponential phase at pH 7.5 (37 degrees C) and then incubated for 30 min under the various stress conditions in the presence of 14C-labelled amino acids followed by cell extraction, protein separation by 2D gel electrophoresis and image analysis of the resulting autoradiograms . Using consistent twofold or greater changes in IOD % as a measure, oxidative stress resulted in the upregulation of 69 proteins, 15 of which were oxidation-specific, and in the downregulation of 24 proteins, when compared to the control cells . An acid shock from pH 7.5 to 5.5 enhanced synthesis of 64 proteins, 25 of them acid-specific, while 49 proteins exhibited diminished synthesis . The dilution of BM resulted in the increased formation of 58 proteins, with 11 starvation-specific proteins and 20 showing decreased synthesis . Some 52 and 40 proteins were enhanced by salt and heat stress, with 10 and 6 of these proteins, respectively, specific to the stress . The synthesis of a significant number of proteins was increased by more than one, but not all stress conditions; six proteins were enhanced by all five stress conditions and could be classified as general stress proteins . Clearly, the response of S . mutans to adverse environmental conditions results in complex and diverse alterations in protein synthesis to further cell survival.

Microbiology, 2000 Jan, 146 ( Pt 1), 31 - 9
Identification of a novel glycoprotein-binding activity in Streptococcus pyogenes regulated by the mga gene; Hytonen J et al.; The interaction between Streptococcus pyogenes and the host cell surface is not completely understood . Characterization of the adhesion mechanisms of the bacterium to the host cell surface is needed in order to develop new vaccines and anti-adhesion drugs . The presence of glycoprotein-binding activities among streptococcal strains was investigated . An activity binding to thyroglobulin, fetuin, asialofetuin and mucin but not non-glycosylated proteins was found to be present in the majority of the S . pyogenes strains studied . Cross-inhibition experiments suggested that the glycoproteins share a common structure recognized by the bacteria . The glycoprotein-binding activity was found to be proteinaceous, tightly attached to the bacterial surface and it also mediated the adherence of bacteria to solid surfaces coated with glycoproteins . The activity was found by transposon mutagenesis and complementation to be regulated by the multiple-gene regulator Mga, which has been implicated as a regulator of S . pyogenes virulence factors.

Nephron, 2000 Feb, 84(2), 167 - 76
Cell adhesion molecule expression in murine lupus-like nephritis induced by lipopolysaccharide; Baran D et al.; BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM) are thought to play important roles in leukocyte recruitment to the kidney . We therefore chose to study mesangial cell adhesion molecule expression in vitro, and the role of these molecules in experimental lupus-like nephritis . METHODS AND RESULTS: When cultured murine mesangial cells were stimulated with interferon-gamma (IFgamma) and tumor necrosis factor-alpha (TNFalpha), mRNA levels for ICAM-1 and VCAM markedly increased . These molecules were detected at the cell surface by flow cytometry . Since lipopolysaccharide (LPS) stimulates TNFalpha and IFgamma production in vivo, we treated mice with Streptococcus minnesota LPS in order to study renal adhesion molecule expression . LPS treatment induced mesangial proliferative glomerulonephritis characterized by leukocyte infiltration, and increases in total glomerular cellularity, volume and matrix area . mRNA levels for ICAM-1 and VCAM were increased in the kidneys of LPS-treated versus control mice . ICAM-1 and VCAM molecules were constitutively expressed in renal vascular endothelium . At 3 and 5 weeks, this vascular staining intensified, and some ICAM-1 and VCAM expression was induced in the glomerular mesangium . ICAM-1 and VCAM induction occurred early and correlated in time with leukocyte infiltration . CONCLUSION: Interactions between cell adhesion molecules expressed by intrinsic glomerular cells and infiltrating leukocytes play a role in the initiation of LPS-induced lupus-like nephritis . These observations are potentially relevant to the understanding and treatment of certain types of human glomerulonephritis .

CLAO J, 2000 Jan, 26(1), 40 - 3
Infectious crystalline keratopathy; Sharma N et al.; PURPOSE: To review the diagnosis, microbial and pathological features, pathogenesis, and treatment of infectious crystalline keratopathy (ICK) . METHODS: We reviewed the literature on infectious crystalline keratopathy . RESULTS AND CONCLUSIONS: ICK is an indolent corneal infection in which needle-like, branching crystalline opacities are seen within the corneal stroma, in the absence of appreciable corneal or anterior segment inflammation . In most cases it occurs as a complication of corneal surgery and keratitis, with an alpha-hemolytic Streptococcus being the cause of infection . Discontinuation of topical steroids with aggressive antibiotic therapy may suffice, but continued infection, vascularization, or scar formation may affect visual acuity and require penetrating keratoplasty.

Kansenshogaku Zasshi, 1999 Dec, 73(12), 1187 - 93
{Resistance against oral antibiotics to Streptococcus pneumoniae isolated from adult respiratory tract infections}; Matsumoto K et al.; The resistance against oral antibiotics to Streptococcus pneumoniae (S . pneumoniae) isolated from adult patients with respiratory tract infections in the Kurume area in 1998 was studied . The frequency of resistant strains, which were isolated penicillin-intermediate S . pneumoniae and resistant S . pneumoniae (PISP, PRSP) were both 41.2% . We examined the minimal inhibitory concentrations (MIC) of oral antibiotics and the susceptibility ratio of the strains for the drugs based on the breakpoint MIC . The breakpoint MIC of pneumonia against oral beta-lactam antibiotics to PISP, PRSP, which were determined by Japan Society of Chemotherapy, were high in the order of FRPM > CDTR, CFPN > CFTM > CFDN, CPDX . In the case of the new oral quinolones, DU6859a > SPFX > LVFX > CPFX showed good results, in this order, DU6859a showed the most significant inhibitory effect to PISP, PRSP (MIC90 0.06 microgram/ml) . By serotyping the percentage of 19, 6, 23 was 42.9%, 21.4% and 14.3%.

Biophys J, 2000 Feb, 78(2), 626 - 51
An electrostatic mechanism closely reproducing observed behavior in the bacterial flagellar motor; Walz D et al.; A mechanism coupling the transmembrane flow of protons to the rotation of the bacterial flagellum is studied . The coupling is accomplished by means of an array of tilted rows of positive and negative charges around the circumference of the rotor, which interacts with a linear array of proton binding sites in channels . We present a rigorous treatment of the electrostatic interactions using minimal assumptions . Interactions with the transition states are included, as well as proton-proton interactions in and between channels . In assigning values to the parameters of the model, experimentally determined structural characteristics of the motor have been used . According to the model, switching and pausing occur as a consequence of modest conformational changes in the rotor . In contrast to similar approaches developed earlier, this model closely reproduces a large number of experimental findings from different laboratories, including the nonlinear behavior of the torque-frequency relation in Escherichia coli, the stoichiometry of the system in Streptococcus, and the pH-dependence of swimming speed in Bacillus subtilis.

Appl Environ Microbiol, 2000 Feb, 66(2), 659 - 63
Inhibition of Streptococcus mutans NS adhesion to glass with and without a salivary conditioning film by biosurfactant- releasing Streptococcus mitis strains; van Hoogmoed CG et al.; The release of biosurfactants by adhering microorganisms as a defense mechanism against other colonizing strains on the same substratum surface has been described previously for probiotic bacteria in the urogenital tract, the intestines, and the oropharynx but not for microorganisms in the oral cavity . Two Streptococcus mitis strains (BA and BMS) released maximal amounts of biosurfactants when they were grown in the presence of sucrose and were harvested in the early stationary phase . The S . mitis biosurfactants reduced the surface tensions of aqueous solutions to about 30 to 40 mJ m(-2) . Biochemical and physicochemical analyses revealed that the biosurfactants released were glycolipids . An acid-precipitated fraction was extremely surfactive and was identified as a rhamnolipidlike compound . In a parallel-plate flow chamber, the number of Streptococcus mutans NS cells adhering to glass with and without a salivary conditioning film in the presence of biosurfactant-releasing S . mitis BA and BMS (surface coverage, 1 to 4%) was significantly reduced compared with the number of S . mutans NS cells adhering to glass in the absence of S . mitis . S . mutans NS adhesion in the presence of non-biosurfactant-releasing S . mitis BA and BMS was not reduced at all . In addition, preadsorption of isolated S . mitis biosurfactants to glass drastically reduced the adhesion of S . mutans NS cells and the strength of their bonds to glass, as shown by the increased percentage of S . mutans NS cells detached by the passage of air bubbles through the flow chamber . Preadsorption of the acid-precipitated fraction inhibited S . mutans adhesion up to 80% in a dose-responsive manner . These observations indicate that S . mitis plays a protective role in the oral cavity and protects against colonization of saliva-coated surfaces by cariogenic S . mutans.

Abdom Imaging, 2000 Jan-Feb, 25(1), 55 - 8
Arteriovenous fistula secondary to iliac mycotic aneurysm: helical CT findings; Alarcon M et al.; We describe the case of a 59-year-old man who presented a mycotic aneurysm of the common right iliac artery due to Streptococcus agalactiae and developed an arteriovenous fistula within the inferior vena cava secondary to spontaneous rupture of the aneurysm . The clinical syndrome, helical computed tomographic, and angiographic findings are described and discussed.

Mol Microbiol, 2000 Jan, 35(2), 251 - 9
Adaptation to the environment: Streptococcus pneumoniae, a paradigm for recombination-mediated genetic plasticity?
Claverys JP, Prudhomme M, Mortier-Barriere I, Martin B.
Genetic plasticity plays a central role in the biology of the human pathogen Streptococcus pneumoniae . This is illustrated by the existence of at least 90 different capsular types (the polysaccharide capsule has an essential antiphagocytic function) as well as by the rapid emergence of penicillin-resistant (PenR) pneumococcal isolates . Natural genetic transformation is believed to be essential for this genetic plasticity; capsular types can be switched by intraspecies transformation, whereas interspecies transformation is responsible for the appearance, in the PenR isolates, of mosaic pbp genes, which encode proteins with reduced affinity for penicillin . Data on the regulation of competence for transformation in S . pneumoniae, on the control of intra- and interspecies genetic exchange and on the shuffling and capture of exogenous sequences during transformation are reviewed . Possible links between transformation and changes in environmental conditions are discussed, and the adaptive 'strategy' deduced for S . pneumoniae is compared with that of Escherichia coli.

Ann Intern Med, 2000 Feb 1, 132(3), 182 - 90
Epidemiologic relation between HIV and invasive pneumococcal disease in San Francisco County, California; Nuorti JP et al.; BACKGROUND: Patients with AIDS have a high incidence of invasive pneumococcal disease, but no population-based data are available on secular trends or rates of this disease in specific demographic groups . OBJECTIVE: To compare clinical characteristics, rates, and trends of pneumococcal disease in HIV-infected and non-HIV-infected persons . DESIGN: Population-based laboratory surveillance and chart review . SETTING: All of the 13 microbiology laboratories in San Francisco County, California . PATIENTS: Persons who had a sterile site culture that was positive for Streptococcus pneumoniae between October 1994 and June 1997 . MEASUREMENTS: Stratified incidence rates and adjusted rate ratios, serotyping of isolates, and comparison of secular trends and rates according to census tract by Poisson regression . RESULTS: Persons infected with HIV accounted for 54.2% of 399 patients 18 to 64 years of age who had pneumococcal disease . The incidence of pneumococcal disease per 100 000 person-years was 35.0 cases overall and 802.9 cases in patients with AIDS . Compared with persons who were not known to be HIV-infected, the rate ratio for patients with AIDS was 46:0 (95% CI, 36.0 to 58.9); 55.2% of cases were attributable to HIV . In HIV-infected patients, 82.5% of isolates were serotypes that are included in the pneumococcal polysaccharide vaccine . The incidence of pneumococcal disease in black patients with AIDS (2384.6 cases per 100 000 person-years) was 5.4 times that in nonblack patients with AIDS . Rates by census tract were inversely associated with income (P < 0.001), During the study period, the incidence of pneumococcal disease decreased from 10.6 cases per 1000 person-years to 4.2 cases per 1000 person-years in patients with AIDS (P = 0.004, Poisson regression) . CONCLUSIONS: In a community with a high prevalence of HIV infection, much of the burden of pneumococcal disease was attributable to AIDS . High incidence rates were seen in young adults and especially in black persons . Efforts to increase pneumococcal vaccination rates should target HIV-infected adults, particularly those living in poor urban areas.

Am J Otol, 2000 Jan, 21(1), 36 - 41
Labeling of the glucocorticoid receptor and Na,K-ATPase in a rat otitis media model; Hultcrantz M et al.; HYPOTHESIS: Glucocorticoid hormones exert an influence on the inflammatory response of the middle ear during acute otitis media . Rats with experimentally induced purulent otitis media were given either glucocorticoid hormones in excess or a glucocorticoid hormone blocker that deprived the animals of the hormone . BACKGROUND: Acute otitis media is a common inflammatory disease among children . Streptococcus pneumoniae is the most usual causative agent . The standard treatment today is phenoxymethylpenicillin . The role of glucocorticoid hormones in inflammatory reactions in the middle ear has been widely debated . METHODS: In an otitis media model, a suspension of pneumococci was inoculated into the bulla of the rat, after the animals were pretreated with either a dose of corticosteroid hormones or the glucocorticoid receptor blocking agent RU 486 . Rats with induction of otitis media only, but no pretreatment, were used as control subjects, as were the left control-operated ears of all rats . The inflammatory response in the inner ear and in the middle ear was evaluated . The presence of glucocorticoid receptors and the enzyme Na,K-ATPase was investigated with immunohistochemistry . RESULTS: The inflammatory response in the animals with untreated otitis media and in the group with otitis media in rats pretreated with the receptor blocker was much more extensive than in the group of animals pretreated with corticosteroids . In the corticosteroid-treated group, the tympanic membrane and the mucous membrane of the middle ear were less edematous, but the middle ear cavity contained more pus . Only a few lymphocytes were found in the inner ears of these rats . When the inner ear was labeled with antibodies against glucocorticoid receptors, there seemed to be no difference between the labeling patterns in the three groups . This was also the case for antibody labeling against Na,K-ATPase . CONCLUSION: The present results indicate that the reaction in the middle ear mucous membrane is more pronounced in rats that had been pretreated with the hormone receptor blocking drug . An increase of corticosteroid hormone levels during the inflammatory process seem to diminish the reaction in the tympanic membrane and the middle ear mucosa . Neither the hormone receptor blocking drug nor the steroid hormones change the content of glucocorticoid receptors and Na,K-ATPase in the inner ear in the otitis media rat model.

Jpn Circ J, 2000 Jan, 64(1), 83 - 6
Purulent pericarditis due to group B streptococcus and mycotic aneurysm of the ascending aorta: case report; Akashi Y et al.; A 61-year-old female, with a history of uterine and cervical cancer treated with radical hysterectomy and 2 years of postoperative chemotherapy, presented to the emergency department with dyspnea on exertion . Computed tomography of the chest revealed a large pericardial effusion and a sacciform aneurysm of the ascending aorta . The patient subsequently underwent emergency pericardiocentesis with drainage of approximately 330 ml of a bloody and turbid effusion . Cultures from the effusion yielded group B streptococcus . Multiple organ failure and disseminated intravascular coagulation syndrome occurred in the acute phase, but gradually improved with continuous antibiotic therapy . On the 194th hospital day, in situ reconstruction of the ascending aorta was successfully performed using a synthetic graft . Although rarely reported, both purulent bacterial pericarditis and mycotic aneurysm can be life-threatening.

FEMS Microbiol Lett, 2000 Feb 1, 183(1), 165 - 9
Streptococcus mutans strain N produces a novel low molecular mass non-lantibiotic bacteriocin; Balakrishnan M et al.; Streptococcus mutans strain N was shown to have bacteriocin production and immunity characteristics consistent with those of Group I mutacin-producing strains of S . mutans . The bacteriocin mutacin N was purified from agar cultures of S . mutans strain N using XAD andp6 reversed phase chromatography . The molecular mass of mutacin N was 4806 Da and the entire 49 amino acid sequence was determined by N-terminal sequencing . Database searches indicate that mutacin N is a novel bacteriocin, but with some homology to the protein IIC domain of a hypothetical sugar-phosphotransferase enzyme from Acholeplasma florum.

Vaccine, 2000 Jan 18, 18(13), 1218 - 26
Salivary anti-capsular antibodies in infants and children immunised with Streptococcus pneumoniae capsular polysaccharides conjugated to diphtheria or tetanus toxoid; Korkeila M et al.; Saliva samples of infants and children immunised with pneumococcal vaccines were analysed for anti-polysaccharide (PS) antibodies against the Streptococcus pneumoniae (Pnc) vaccine serotypes 6B, 14, 19F, and 23F . The children received Pnc conjugate vaccine (1, 3, or 10 micrograms of PSs conjugated to diphtheria or tetanus toxoid) or placebo at 2, 4, and 6 months . At 7 months of age salivary PS antibodies were detected rarely . All children received Pnc conjugate or PS vaccine at 14 months of age . At 15 months, both IgA and IgG anti-Pnc PS were found, anti-19F and anti-14 antibodies occurring most frequently and in the highest concentrations . IgA was in the secretory form and predominantly IgA1 . A negative dose dependency was observed in IgA anti-19F response . In general, no clear differences in salivary antibody responses were found between the children primed with conjugate vaccine in infancy and those who received their first Pnc vaccine at 14 months of age, suggesting that priming with Pnc conjugate vaccines does not lead to remarkable mucosal memory responses.

J Bacteriol, 2000 Feb, 182(4), 1162 - 6
Single-molecule imaging of interaction between dextran and glucosyltransferase from Streptococcus sobrinus; Kaseda K et al.; Using total internal reflection fluorescence microscopy, we directly observed the interaction between dextran and glucosyltransferase I (GTF) of Streptococcus sobrinus . Tetramethylrhodamine (TMR)-labeled GTF molecules were individually imaged as they were associating with and then dissociating from the dextran fixed on the glass surface in the evanescent field . Similarly dynamic behavior of TMR-labeled dextran molecules was also observed on the GTF-fixed surface . The duration of the stay on the surface (dwell time) was measured for each of these molecules by counting the number of video frames that had recorded the image . A histogram of dwell time for a population of several hundred molecules indicated that the GTF-dextran interaction obeyed an apparent first-order kinetics . The rate constraints estimated for TMR-labeled GTF at pH 6.8 and 25 degrees C in the absence and presence of sucrose were 9.2 and 13.3 s(-1), respectively, indicating that sucrose accelerated the dissociation of GTF from dextran . However, the accelerated rate was still much lower than the catalytic center activity of GTF (> or = 25 s(-1)) under comparable conditions.

J Bacteriol, 2000 Feb, 182(4), 1016 - 23
Barriers to genetic exchange between bacterial species: Streptococcus pneumoniae transformation; Majewski J et al.; Interspecies genetic exchange is an important evolutionary mechanism in bacteria . It allows rapid acquisition of novel functions by transmission of adaptive genes between related species . However, the frequency of homologous recombination between bacterial species decreases sharply with the extent of DNA sequence divergence between the donor and the recipient . In Bacillus and Escherichia, this sexual isolation has been shown to be an exponential function of sequence divergence . Here we demonstrate that sexual isolation in transformation between Streptococcus pneumoniae recipient strains and donor DNA from related strains and species follows the described exponential relationship . We show that the Hex mismatch repair system poses a significant barrier to recombination over the entire range of sequence divergence (0.6 to 27%) investigated . Although mismatch repair becomes partially saturated, it is responsible for 34% of the observed sexual isolation . This is greater than the role of mismatch repair in Bacillus but less than that in Escherichia . The remaining non-Hex-mediated barrier to recombination can be provided by a variety of mechanisms . We discuss the possible additional mechanisms of sexual isolation, in view of earlier findings from Bacillus, Escherichia, and Streptococcus.

Cranio, 1999 Jul, 17(3), 221 - 7
Regeneration ad integrum of the condyle head in a patient with temporomandibular disorders; Learreta JA; A 14-year-old who had suffered from a beta-hemolytic streptococcus infection presented with serious temporomandibular disorders, including a reabsorption of the condyle head on the right side, and reabsorption in the cavern of the left side . Her masticatory muscles were electronically deprogramed, achieving a mandibular position supported by a relaxed musculature . The patient's signs and symptoms subsequently disappeared . Study of the magnetic resonance image a year later clearly showed a regeneration ad integrum of the condyle head and a spontaneous reinsertion of the articular disk . The results suggest the need for use of electronic elements in order to treat patients with temporomandibular disorders effectively.

Am J Dent, 1999 Jun, 12(3), 148 - 50
Residual antimicrobial activity associated with a chlorhexidine endodontic irrigant used with sodium hypochlorite; White RR et al.; PURPOSE: To evaluate the in vitro efficacy of 2.0% chlorhexidine gluconate (CH) as an endodontic irrigant combined with the traditional irrigant, sodium hypochlorite (SH) . MATERIALS AND METHODS: Extracted single-rooted human teeth were instrumented using one of three regimens: CH alone; SH alone until instrumentation with the last file, at which time CH was used as the filing irrigant; or SH alone followed by a single rinse with CH . After instrumentation, each root canal was dried with endodontic paper points, filled with sterile water, and maintained in a water-saturated environment . At 6, 12, 24, 48 and 72 hours after instrumentation, the root canal fluid was absorbed with an endodontic paper point, and the canal was irrigated and refilled with sterile water . The paper points containing root canal fluids were assayed for antimicrobial activity by placing them on agar plates inoculated with Streptococcus mutans, and measuring zones of inhibition after incubation . RESULTS: Comparisons of the results obtained from the three treatment regimens indicated there were no significant differences (P > 0.5) in the relative in vitro antimicrobial activity remaining in the three groups of teeth.

Microb Drug Resist, 1999 Winter, 5(4), 271 - 8
Prevalence and patterns of resistance of Streptococcus pneumoniae strains isolated from carriers attending day care centers in the area of Athens; Tsolia M et al.; The prevalence and patterns of Streptococcus pneumoniae resistance to antibiotics was examined in 146 nasopharyngeal carrier strains obtained during April and May, 1997, from 382 healthy children attending eight day care centers (DCCs) in the area of Athens . Reduced susceptibility to at least one antibiotic was found in 32.6% as follows: penicillin 11.4% (intermediate), cefotaxime 0.8% (intermediate), trimethoprim-sulfamethoxazole 22.7%, erythromycin 13.6%, tetracycline 11.4%, chloramphenicol 8.3% . Most of the nonsusceptible to penicillin isolates belonged to serogroups 23, 9, and 19 . Multidrug resistance was detected in 11.4% of S . pneumoniae isolates including five penicillin nonsusceptible serogroup 23 strains . More than half of the multidrug resistant strains were susceptible to penicillin and belonged to serogroups 6 (4), 23 (1), 19 (1), and 1(1) . Strains that belonged to the same serogroup/serotype and had identical resistance patterns appeared to cluster in some DCCs . Antibiotic use in the previous month was associated with reduced susceptibility to penicillin (p = 0.007) and multidrug resistance (p = 0.012) . In conclusion, a moderate prevalence of reduced susceptibility to penicillin in pneumococcal carrier strains was found in our community . Multidrug resistance was common and was often associated with susceptibility to penicillin . Several distinct patterns of resistance were observed, suggesting the spread of resistant clones to our country.

Microb Drug Resist, 1999 Winter, 5(4), 247 - 52
Calcium signaling in Streptococcus pneumoniae: implication of the kinetics of calcium transport; Trombe MC; The kinetics and pharmacological characterization of a Na+/Ca2+ exchange system, essential for the growth of the extracellular pathogen Streptococcus pneumoniae in high-calcium media, demonstrated that calcium transport, in addition to its role in calcium homeostasis, is involved in the induction of autolysis and of competence for genetic transformation . These responses are expressed respectively in cultures entering the stationary phase and growing with exponential rates . Experimental virulence also appears to be modulated by the kinetics of calcium transport . Calcium transport in S . pneumoniae is electrogenic and shows sigmoidicity, indicating a cooperative mechanism with an inflexion point at 1 mM Ca2+ . Mutant strains with Hill number values of 4 and 1, compared to 2 in the wild-type strain, were isolated . These changes were associated with altered regulation of competence and autolysis, and also with reduced experimental virulence . By contrast, they could not be related to a specific calcium requirement for growth . This indicates that the cooperativity of Ca2+ transport is not involved in vegetative growth, but rather regulates competence and autolysis . Competence and autolysis represent two growth-phase-dependent responses to an oligopeptide-activator exported to the medium, the competence-stimulating peptide . Addition of this activator to noncompetent cells, triggers net and transient 45Ca2+ influx . One effect of the activator might be to activate a calcium transporter by enhancing its cooperativity . In addition to an increase in intracellular calcium, a transient membrane depolarization induced by electrogenic calcium influx may be part of the signaling mechanism . The competence activator is a quorum-sensing molecule whose synthesis is autoregulated . This regulation might involve calcium-mediated signaling . As an extracellular pathogen, S . pneumoniae probably develops in niches with variable calcium concentration . Interestingly, virulence depends strongly upon the kinetics of Ca2+ transport . Regulation of calcium influx may represent a common mechanism of sensing the environment, if the Na+/Ca2+ exchanger is the target for external mediators including the competence activator.

Microb Drug Resist, 1999 Winter, 5(4), 241 - 6
Acquisition of new capsular genes among clinical isolates of antibiotic-resistant Streptococcus pneumoniae; Ramirez M et al.; Antibiotic-resistant clones of Streptococcus pneumoniae are recognizable through a combination of unique molecular, microbiological, and serological properties . In the course of surveillance of epidemic clones of S . pneumoniae, several isolates were identified that shared the clone-specific pulsed-field gel electrophoretic (PFGE) pattern and antibiotype but expressed serotypes atypical for the particular clone . A selected group of isolates belonging to the Spanish/USA clone but expressing serotypes 19, 14, or 3, instead of the expected serotype 23F, were tested using DNA probes for each of the 18 open reading frames (ORFs) of the 23F capsular locus . In no case were there any 23F-specific genes retained, with the possible exception of genes already known to be common to the capsular loci involved . Analysis of the sequence of the capsular locus of a penicillin-resistant serotype 23F isolate from Mexico showed that part of the cpsA gene of this strain, as well as genes cpsQ and cpsR, had high degrees of identity to the sequence of the homologous genes in isolates expressing serotype 19F . The capsular locus of this Mexican strain may have originated from an in vivo capsular switch event in which the original 19F locus was replaced by 23F-specific capsular genes.

Genomics, 1999 Dec 15, 62(3), 500 - 7
Optimized multiplex PCR: efficiently closing a whole-genome shotgun sequencing project; Tettelin H et al.; A new method has been developed for rapidly closing a large number of gaps in a whole-genome shotgun sequencing project . The method employs multiplex PCR and a novel pooling strategy to minimize the number of laboratory procedures required to sequence the unknown DNA that falls in between contiguous sequences . Multiplex sequencing, a novel procedure in which multiple PCR primers are used in a single sequencing reaction, is used to interpret the multiplex PCR results . Two protocols are presented, one that minimizes pipetting and another that minimizes the number of reactions . The pipette optimized multiplex PCR method has been employed in the final phases of closing the Streptococcus pneumoniae genome sequence, with excellent results .

Pediatr Infect Dis J, 2000 Jan, 19(1), 41 - 6
Impact of azithromycin on oropharyngeal carriage of group A Streptococcus and nasopharyngeal carriage of macrolide-resistant Streptococcus pneumoniae; Morita JY et al.; BACKGROUND: Invasive group A streptococcal (GAS) infections are a cause of serious morbidity and high mortality . There is a need for a simple, effective antimicrobial regimen that could be used to prevent invasive GAS disease in high risk situations . To assess azithromycin as a chemoprophylactic agent, we evaluated its efficacy for eradication of oropharyngeal (OP) GAS and its impact on the nasopharyngeal (NP) colonization rate of macrolide-resistant Streptococcus pneumoniae . METHODS: We obtained OP and NP swabs for GAS and pneumococcus culture, respectively, from 300 schoolmates of a child with an invasive GAS infection . GAS culture-positive students were treated with daily azithromycin (12 mg/kg/day) for 5 days . We obtained follow-up OP and NP swabs at 9 (Day 17) and 24 (Day 32) days post-treatment from those students identified as GAS carriers on Day 0 and determined macrolide susceptibility of GAS and pneumococcal isolates . RESULTS: Of the 300 students swabbed 152 (50%) carried GAS in their oropharynx . On Day 17, efficacy of azithromycin for GAS eradication was 95% (140 of 147) for all students . NP colonization rates for pneumococci decreased from 46% (67 of 146) to 12% (17 of 144; P < 0.001) by Day 17 and to 20% (27 of 137; P < 0.001) by Day 32 . The prevalence of erythromycin-resistant pneumococcal isolates increased from 2% (3 of 146) to 4% (6 of 144) by Day 17 and to 8% (11 of 137; P = 0.04) by Day 32 . CONCLUSIONS: Azithromycin is an effective short course regimen for eradication of oropharyngeal GAS . However, azithromycin selected for macrolide-resistant strains of pneumococci . These findings highlight the importance of determining the appropriate circumstances for antimicrobial prophylaxis to prevent invasive GAS infections.

FEMS Immunol Med Microbiol, 2000 Feb, 27(2), 111 - 6
Protective effect of beta-glucan against systemic Streptococcus pneumoniae infection in mice; Hetland G et al.; The antimicrobial effect of soluble beta-1,3-D-glucan from Sclerotinia sclerotiorum (SSG) was examined in mice experimentally infected intraperitoneally (i.p.) with Streptococcus pneumoniae serotypes 4 and 6B . SSG was administered i.p . either 3 days before challenge or 3-48 h after challenge . The number of bacteria in blood samples and the mouse survival rates were recorded . Pre-challenge SSG administration protected dose-dependently against both S . pneumoniae type 4 and 6B infections . SSG injected 24 h post-challenge had a curative effect against type 6B but not type 4 pneumococcal infection . The data demonstrate that SSG administered systemically protects against pneumococcal infection in mice.

Pharmacotherapy, 2000 Jan, 20(1), 110 - 7
Duration of penicillin prophylaxis in sickle cell anemia: issues and controversies; Pai VB et al.; Functional asplenia occurs in 94% of patients with homozygous sickle cell anemia by 5 years of age and may result in fatal septicemia due to encapsulated microorganisms such as Streptococcus pneumoniae . Penicillin prophylaxis in these patients significantly reduces the risk of septicemia; however, continuation of prophylaxis beyond 5 years of age is controversial, since the risk of developing septicemia is reduced after this age and prolonged prophylaxis may lead to emergence of penicillin resistance . Although reports of penicillin-resistant pneumococci in patients receiving penicillin prophylaxis are conflicting, the prevalence of these organisms in the general population in North America increased from 5% in 1989 to more than 35% in 1997 . Discontinuation of prophylaxis after age 5 years may be recommended because of lack of benefit, difficulty maintaining compliance, reduced risk of developing pneumococcal bacteremia after that age, and increase in prevalence of penicillin-resistant pneumococci worldwide.

Public Health Rev, 1998, 26(4), 317 - 30
Infective endocarditis in a tertiary-care hospital in southern Israel; Borer A et al.; During the years 1980-1994, 84 patients were treated in our institution due to suspected infective endocarditis (IE) . Seventy-one of these episodes occurring in 71 patients, classified definite or possible according to the Duke criteria, were retrospectively analyzed in this study . There were 52 cases of native valve endocarditis, 7 cases of early prosthetic valve endocarditis, and 12 cases of late prosthetic valve endocarditis . The incidence of IE did not change significantly during the study period . The overall mortality rate was 15% . Only one case of drug addiction appeared in our series despite its growing frequency in Israel . Rheumatic heart disease remained the main underlying cardiac condition and Streptococcus viridans remained the most common pathogen . Streptococcus bovis was found to be a significant pathogen causing IE in our patient population, while Staphylococcus aureus appeared to be less frequent . The Duke criteria significantly classified a greater proportion of cases as definitive, as opposed to the von Reyn criteria . Fewer cases were rejected by the Duke criteria, especially culture-negative cases, and those without histopathological confirmation . Application of the Duke criteria permits a more consistent approach to the diagnosis of IE, even in a non-drug-addict patient population.

Surg Today, 1999, 29(12), 1233 - 6
An additional dose of cefazolin for intraoperative prophylaxis; Ohge H et al.; We examined the pancreatic tissue concentrations of cefazolin in ten patients undergoing pancreatectomy, and determined the optimal intraoperative time to deliver a repeat dose of cefazolin . An intravenous bolus dose of 1 g cefazolin was administered at the time of skin incision . Peripheral blood, subcutaneous adipose tissue, and peritoneal samples were obtained intraoperatively every hour for 4 h after the antibiotic was first administered, and pancreatic tissue samples were obtained at the time of pancreatectomy . To determine adequate tissue levels of cefazolin, minimum inhibitory concentrations (MIC) were measured for four bacterial species, namely 360 isolates of methicillin-sensitive Staphylococcus aureus (MSSA), 204 isolates of Klebsiella pneumoniae, 314 isolates of Escherichia coli, and 30 isolates of Streptococcus spp . The antibiotic concentrations in adipose tissue and peritoneum 3 h after the administration of cefazolin were lower than the MIC80 for K . pneumoniae, E . coli, and Streptococcus spp . Most pancreatic tissue samples showed antibiotic concentrations greater than the MIC80 for these bacterial species; however, those from four patients complicated by severe chronic pancreatitis, massive intraoperative bleeding, or obesity showed concentrations lower than the MIC80 . Thus, we recommend that a second dose of cefazolin be given 3 h after the first administration to maintain adequate levels of antibiotic activity.

Thorax, 2000 Feb, 55(2), 133 - 7
Diagnosis of pneumococcal pneumonia by polymerase chain reaction (PCR) in whole blood: a prospective clinical study; Lorente ML et al.; BACKGROUND: Streptococcus pneumoniae is the leading cause of community acquired pneumonia; however, only a small proportion of cases can be detected by conventional methods . The ability of the polymerase chain reaction (PCR) test performed on whole blood samples to identify patients with pneumococcal pneumonia was investigated . METHODS: One hundred and fourteen consecutive adult patients with community acquired pneumonia were evaluated by a wide battery of diagnostic tests in order to determine the aetiology . Blood samples from these patients and 50 controls were also tested by the nested PCR test to detect selected pneumolysin gene fragments of S pneumoniae . RESULTS: The patients were divided into four groups: (1) 40 patients with pneumococcal pneumonia in 22 of whom (55%) the PCR was positive (eight of 11 with bacteraemia and 14 of 29 without); (2) 30 with pneumonia due to other pathogens in all of whom the PCR was negative; (3) 44 with pneumonia of unknown aetiology in 14 of whom (32%) PCR was positive, and (4) 50 controls in whom the PCR test was positive in two (4%) . Thus, the sensitivity of the test was 55% and the specificity 100% (81% if positive PCR tests among undiagnosed patients are considered as false positive results) . CONCLUSION: PCR applied to whole blood samples appears to be a sensitive and very specific diagnostic test for identifying patients with pneumococcal pneumonia with a potential application in clinical practice.

Antimicrob Agents Chemother, 2000 Feb, 44(2), 414 - 7
In vitro development of resistance to telithromycin (HMR 3647), four macrolides, clindamycin, and pristinamycin in Streptococcus pneumoniae; Davies TA et al.; The ability of 50 sequential subcultures in subinhibitory concentrations of telithromycin (HMR 3647), azithromycin, clarithromycin, erythromycin A, roxithromycin, clindamycin, and pristinamycin to select for resistance was studied in five macrolide-susceptible and six macrolide-resistant pneumococci containing mefE or ermB . Telithromycin selected for resistance less often than the other drugs.

Antimicrob Agents Chemother, 2000 Feb, 44(2), 393 - 5
Acquisition of chloramphenicol resistance by the linearization and integration of the entire staphylococcal plasmid pC194 into the chromosome of Streptococcus pneumoniae; Widdowson CA et al.; Chloramphenicol resistance in Streptococcus pneumoniae was associated with cat, which has 100% identity with cat(pC194) from Staphylococcus aureus . Inverse PCR with primers specific for pC194 confirmed that in some isolates the entire staphylococcal plasmid was present in the S . pneumoniae chromosome, with linearization having occurred between cat(pC194) and the origin of replication.

Antimicrob Agents Chemother, 2000 Feb, 44(2), 320 - 5
Engineering the specificity of antibacterial fluoroquinolones: benzenesulfonamide modifications at C-7 of ciprofloxacin change its primary target in Streptococcus pneumoniae from topoisomerase IV to gyrase; Alovero FL et al.; We have examined the antipneumococcal mechanisms of a series of novel fluoroquinolones that are identical to ciprofloxacin except for the addition of a benzenesulfonylamido group to the C-7 piperazinyl ring . A number of these derivatives displayed enhanced activity against Streptococcus pneumoniae strain 7785, including compound NSFQ-105, bearing a 4-(4-aminophenylsulfonyl)-1-piperazinyl group at C-7, which exhibited an MIC of 0.06 to 0.125 microg/ml compared with a ciprofloxacin MIC of 1 microg/ml . Several complementary approaches established that unlike the case for ciprofloxacin (which targets topoisomerase IV), the increased potency of NSFQ-105 was associated with a target preference for gyrase: (i) parC mutants of strain 7785 that were resistant to ciprofloxacin remained susceptible to NSFQ-105, whereas by contrast, mutants bearing a quinolone resistance mutation in gyrA were four- to eightfold more resistant to NSFQ-105 (MIC of 0.5 microg/ml) but susceptible to ciprofloxacin; (ii) NSFQ-105 selected first-step gyrA mutants (MICs of 0.5 microg/ml) encoding Ser-81-to-Phe or -Tyr mutations, whereas ciprofloxacin selects parC mutants; and (iii) NSFQ-105 was at least eightfold more effective than ciprofloxacin at inhibiting DNA supercoiling by S . pneumoniae gyrase in vitro but was fourfold less active against topoisomerase IV . These data show unequivocally that the C-7 substituent determines not only the potency but also the target preference of fluoroquinolones . The importance of the C-7 substituent in drug-enzyme contacts demonstrated here supports one key postulate of the Shen model of quinolone action.

Antimicrob Agents Chemother, 2000 Feb, 44(2), 255 - 60
Efficacy of a new cream formulation of mupirocin: comparison with oral and topical agents in experimental skin infections; Gisby J et al.; A new cream formulation of mupirocin developed to improve patient compliance was compared with systemic and topical antibiotics commonly used to treat primary and secondary skin infections . A mouse surgical wound model infected with Staphylococcus aureus or Streptococcus pyogenes was used . Topical treatment was applied at 4 and 10 h postinfection or oral treatment at a clinically relevant dose was administered 4, 8, and 12 h postinfection; treatments were continued three times daily for a further 3 days . Mupirocin cream was significantly more effective than (P < 0.01; two of eight studies) or not significantly different from (six of eight studies) mupirocin ointment in reducing bacterial numbers . Mupirocin cream was similar in efficacy to oral flucloxacillin but significantly more effective (P < 0.001) than oral erythromycin . It was also similar in efficacy to cephalexin against S . pyogenes but superior against S . aureus (P < 0.01) . Mupirocin cream had a similar efficacy to fusidic acid cream against S . aureus but was significantly superior against S . pyogenes (P < 0.01) . A hamster impetigo model infected with S . aureus was also used . Topical or oral treatment was administered at 24 and 30 h postinfection (also 36 h postinfection for oral therapy) and then three times daily for a further 2 days . On day 5, mupirocin cream was significantly more effective than mupirocin ointment in one study (P < 0.01) and of similar efficacy in the other two studies . Mupirocin cream was not significantly different from fusidic acid cream or neomycin-bacitracin cream, but it was significantly superior (P < 0.01) to oral erythromycin and cephalexin . Mupirocin cream was as effective as, or superior to, oral and other topical agents commonly used for skin infections.

Indian J Chest Dis Allied Sci, 1999 Jan-Mar, 41(1), 65 - 7
Bacteriology of bronchial secretions in non-tubercular lower respiratory tract infections; Arora U et al.; Fifty samples of bronchial secretions collected from patients of non-tubercular lower respiratory tract infections through fiberoptic bronchoscopy (FOB) were cultured both for aerobic and anaerobic organisms . Thirty-three (66%) samples yielded bacteria . Out of these, thirty were isolated in pure culture and from three, a mixed growth of aerobic and anaerobic micro-organisms was obtained . Aerobic bacteria were the predominant isolates . Stephylococcus aureus (10), pseudomonas (9) and streptococcus pneumoniae (8) were the major aerobic isolates . Ciprofloxacin was found to be the most effective drug against aerobes and metronidazole against anaerobes in vitro susceptibility tests.

Infect Immun, 2000 Feb, 68(2), 925 - 30
Identification of the operon for the sorbitol (Glucitol) Phosphoenolpyruvate:Sugar phosphotransferase system in Streptococcus mutans; Boyd DA et al.; Transposon mutagenesis and marker rescue were used to isolate and identify an 8.5-kb contiguous region containing six open reading frames constituting the operon for the sorbitol P-enolpyruvate phosphotransferase transport system (PTS) of Streptococcus mutans LT11 . The first gene, srlD, codes for sorbitol-6-phosphate dehydrogenase, followed downstream by srlR, coding for a transcriptional regulator; srlM, coding for a putative activator; and the srlA, srlE, and srlB genes, coding for the EIIC, EIIBC, and EIIA components of the sorbitol PTS, respectively . Among all sorbitol PTS operons characterized to date, the srlD gene is found after the genes coding for the EII components; thus, the location of the gene in S . mutans is unique . The SrlR protein is similar to several transcriptional regulators found in Bacillus spp . that contain PTS regulator domains (J . Stulke, M . Arnaud, G . Rapoport, and I . Martin-Verstraete, Mol . Microbiol . 28:865-874, 1998), and its gene overlaps the srlM gene by 1 bp . The arrangement of these two regulatory genes is unique, having not been reported for other bacteria.

Infect Immun, 2000 Feb, 68(2), 921 - 4
Evaluation of the virulence of a Streptococcus pneumoniae neuraminidase-deficient mutant in nasopharyngeal colonization and development of otitis media in the chinchilla model; Tong HH et al.; Considerable evidence has implicated Streptococcus pneumoniae neuraminidase in the pathogenesis of otitis media (OM); however, its exact role has not been conclusively established . Recently, an S . pneumoniae neuraminidase-deficient mutant, DeltaNA1, has been constructed by insertion-duplication mutagenesis of the nanA gene of S . pneumoniae strain D39 . The relative ability of DeltaNA1 and the D39 parent strain to colonize the nasopharynx and to induce OM subsequent to intranasal inoculation and to survive in the middle ear cleft after direct challenge of the middle ear were evaluated in the chinchilla model . Nasopharyngeal colonization data indicate a significant difference in the ability of the DeltaNA1 mutant to colonize as well as to persist in the nasopharynx . The neuraminidase-deficient mutant was eliminated from the nasopharynx 2 weeks earlier than the D39 parent strain . Both the parent and the mutant exhibited similar virulence levels and kinetics during the first week after direct inoculation of the middle ear . The DeltaNA1 neuraminidase-deficient mutant, however, was then completely eliminated from the middle ear by day 10 postchallenge, 11 days before the D39 parent strain . Data from this study indicate that products of the nanA gene have an impact on the ability of S . pneumoniae to colonize and persist in the nasopharynx as well as the middle ear.

Infect Immun, 2000 Feb, 68(2), 796 - 800
Intranasal immunization of mice with a mixture of the pneumococcal proteins PsaA and PspA is highly protective against nasopharyngeal carriage of Streptococcus pneumoniae; Briles DE et al.; Acquisition of pneumococci is generally from carriers rather than from infected individuals . Therefore, to induce herd immunity against Streptococcus pneumoniae it will be necessary to elicit protection against carriage . Capsular polysaccharide-protein conjugates, PspA, and PsaA are known to elicit some protection against nasopharyngeal carriage of pneumococci but do not always completely eliminate carriage . In this study, we observed that PsaA elicited better protection than did PspA against carriage . Pneumolysin elicited no protection against carriage . Immunization with a mixture of PsaA and PspA elicited the best protection against carriage . These results indicate that PspA and PsaA may be useful for the elicitation of herd immunity in humans . As PspA and pneumolysin are known to elicit immunity to bacteremia and pneumonia, their inclusion in a mucosal vaccine may enable such a vaccine to prevent invasive disease as well as carriage.

Infect Immun, 2000 Feb, 68(2), 760 - 6
Immunogenicity of the B monomer of Escherichia coli heat-labile toxin expressed on the surface of Streptococcus gordonii; Ricci S et al.; The B monomer of the Escherichia coli heat-labile toxin (LTB) was expressed on the surface of the human oral commensal bacterium Streptococcus gordonii . Recombinant bacteria expressing LTB were used to immunize BALB/c mice subcutaneously and intragastrically . The LTB monomer expressed on the streptococcal surface proved to be highly immunogenic, as LTB-specific immunoglobulin G (IgG) serum titers of 140,000 were induced after systemic immunization . Most significantly, these antibodies were capable of neutralizing the enterotoxin in a cell neutralization assay . Following mucosal delivery, antigen-specific IgA antibodies were found in feces and antigen-specific IgG antibodies were found in sera . Analysis of serum IgG subclasses showed a clear predominance of IgG1 when recombinant bacteria were inoculated subcutaneously, while a prevalence of IgG2a was observed upon intragastric delivery, suggesting, in this case, the recruitment of a Th1 type of immune response.

Infect Immun, 2000 Feb, 68(2), 644 - 50
Role of serotype-specific polysaccharide in the resistance of Streptococcus mutans to phagocytosis by human polymorphonuclear leukocytes; Tsuda H et al.; To clarify the role of cell surface components of Streptococcus mutans in resistance to phagocytosis by human polymorphonuclear leukocytes (PMNs), several isogenic mutants of S . mutans defective in cell surface components were studied with a luminol-enhanced chemiluminescence (CL) assay, a killing assay, and a transmission electron microscope . The CL responses of human PMNs to mutant Xc11 defective in a major cell surface antigen, PAc, and mutant Xc16 defective in two surface glucosyltransferases (GTF-I and GTF-SI) were the same as the response to the wild-type strain, Xc . In contrast, mutant Xc24R, which was defective in serotype c-specific polysaccharide, induced a markedly higher CL response than the other strains . The killing assay showed that human PMNs killed more Xc24R than the parent strain and the other mutants . The transmission electron microscopic observation indicated that Xc24R cells were more internalized by human PMNs than the parental strain Xc . These results may be reflected by the fact that strain Xc24R was more phagocytosed than strain Xc . The CL response of human PMNs to a mutant defective in polysaccharide serotype e or f was similar to the response to Xc24R . Furthermore, mutants defective in serotype-specific polysaccharide were markedly more hydrophobic than the wild-type strains and the other mutants, suggesting that the hydrophilic nature of polysaccharides may protect the bacterium from phagocytosis . We conclude that the serotype-specific polysaccharide, but not the cell surface proteins on the cell surface of S . mutans, may play an important role in the resistance to phagocytosis.

Infect Immun, 2000 Feb, 68(2), 543 - 9
Construction and characterization of an effector strain of Streptococcus mutans for replacement therapy of dental caries; Hillman JD et al.; An effector strain has been constructed for use in the replacement therapy of dental caries . Recombinant DNA methods were used to make the Streptococcus mutans supercolonizing strain, JH1140, lactate dehydrogenase deficient by deleting virtually all of the ldh open reading frame (ORF) . To compensate for the resulting metabolic imbalance, a supplemental alcohol dehydrogenase activity was introduced by substituting the adhB ORF from Zymomonas mobilis in place of the deleted ldh ORF . The resulting clone, BCS3-L1, was found to produce no detectable lactic acid during growth on a variety of carbon sources, and it produced significantly less total acid due to its increased production of ethanol and acetoin . BCS3-L1 was significantly less cariogenic than JH1140 in both gnotobiotic- and conventional-rodent models . It colonized the teeth of conventional rats as well as JH1140 in both aggressive-displacement and preemptive-colonization models . No gross or microscopic abnormalities of major organs were associated with oral colonization of rats with BCS3-L1 for 6 months . Acid-producing revertants of BCS3-L1 were not observed in samples taken from infected animals (reversion frequency, <10(-3)) or by screening cultures grown in vitro, where no revertants were observed among 10(5) colonies examined on pH indicator medium . The reduced pathogenic potential of BCS3-L1, its strong colonization potential, and its genetic stability suggest that this strain is well suited to serve as an effector strain in the replacement therapy of dental caries in humans.

Infect Immun, 2000 Feb, 68(2), 535 - 42
Nonpolar inactivation of the hypervariable streptococcal inhibitor of complement gene (sic) in serotype M1 Streptococcus pyogenes significantly decreases mouse mucosal colonization; Lukomski S et al.; Group A Streptococcus (GAS) is a human pathogen that commonly infects the upper respiratory tract . GAS serotype M1 strains are frequently isolated from human infections and contain the gene encoding the hypervariable streptococcal inhibitor of complement protein (Sic) . It was recently shown that Sic variants were rapidly selected on mucosal surfaces in epidemic waves caused by M1 strains, an observation suggesting that Sic participates in host-pathogen interactions on the mucosal surface (N . P . Hoe, K . Nakashima, S . Lukomski, D . Grigsby, M . Liu, P . Kordari, S.-J . Dou, X . Pan, J . Vuopio-Varkila, S . Salmelinna, A . McGeer, D . E . Low, B . Schwartz, A . Schuchat, S . Naidich, D . De Lorenzo, Y.-X . Fu, and J . M . Musser, Nat . Med . 5:924-929, 1999) . To test this idea, a new nonpolar mutagenesis method employing a spectinomycin resistance cassette was used to inactivate the sic gene in an M1 GAS strain . The isogenic Sic-negative mutant strain was significantly (P < 0.019) impaired in ability to colonize the mouse mucosal surface after intranasal infection . These results support the hypothesis that the predominance of M1 strains in human infections is related, in part, to a Sic-mediated enhanced colonization ability.

Infect Immun, 2000 Feb, 68(2), 511 - 7
Acquired, but not innate, immune responses to Streptococcus pneumoniae are compromised by neutralization of CD40L; Hwang Y et al.; Streptococcus pneumoniae is a significant pathogen of young children and the elderly . Systemic infection by pneumococci is a complex process involving several bacterial and host factors . We have investigated the role of CD40L in host defense against pneumococcal infection . Treatment of mice with MR-1 antibody (anti-CD154/CD40L) markedly reduced antibody responses to the pneumococcal protein PspA, elicited by immunization of purified protein or whole bacteria . In mice immunized with whole bacteria, MR-1 treatment reduced antibody responses to capsular polysaccharides but not cell wall polysaccharides . MR-1 did not suppress antibody responses to isolated capsular polysaccharides but did reduce the production of antibody to a capsular polysaccharide-protein conjugate, indicating that when presented in the context of whole bacteria, the humoral response to capsular polysaccharides is partially T-cell dependent . Despite the reduction of the protective humoral responses to pneumococcal infection, administration of MR-1 had no effect on sepsis, lung infection, or nasal carriage in nonimmune mice inoculated with virulent pneumococci . Thus, short-term neutralization of CD40L does not compromise innate host defenses against pneumococcal invasion.

Antimicrob Agents Chemother, 2000 Feb, 44(2), 462 - 6
Prevalence of gyrA, gyrB, parC, and parE mutations in clinical isolates of Streptococcus pneumoniae with decreased susceptibilities to different fluoroquinolones and originating from Worldwide Surveillance Studies during the 1997-1998 respiratory season; Jones ME et al.; From 8,419 worldwide clinical isolates of Streptococcus pneumoniae obtained during 1997-1998, 69 isolates with reduced susceptibility or resistance to fluoroquinolones (FQs) were molecularly characterized . For the isolates in this prevalence study, only parC (Ser-79-->Tyr) and gyrA (Ser-81-->Phe or Tyr) mutations, especially in combination, were found to contribute significantly to resistance . These mutations influenced the FQ MICs to varying degrees, although the rank order of activity remains independent of mutation type, with ciprofloxacin the least active, followed by levofloxacin, gatifloxacin/grepafloxacin/moxifloxacin/sparfloxaci n/trovafloxacin, and clinafloxacin/sitafloxacin . Efflux likely plays a crucial role in reduced susceptibility for new hydrophilic FQs.

Antimicrob Agents Chemother, 2000 Feb, 44(2), 456 - 7
Resistance to mercury and antimicrobial agents in Streptococcus mutans isolates from human subjects in relation to exposure to dental amalgam fillings; Leistevuo J et al.; Resistance to cefuroxime, penicillin, tetracycline, and mercury is reported for 839 Streptococcus mutans isolates from 209 human study subjects . The MICs of these drugs did not differ for isolates from one dental amalgam group and two nonamalgam subsets: a group with no known exposure to amalgam and a group whose members had their amalgam fillings removed.

Med Decis Making, 2000 Jan-Mar, 20(1), 33 - 8
Does clinical error contribute to unnecessary antibiotic use?
McIsaac WJ, Butler CC.
Patient expectations and physician attitudes are often cited as factors in the overuse of antibiotics . This study examined whether clinical error might also be important . In treating 517 patients with sore throat, family physicians estimated the probability that group A streptococcus infection was present . Two thirds of antibiotics prescribed were to culture-negative patients and therefore considered unnecessary . Physicians overestimated the probability that a group A streptococcal infection was present by an average 33.2% in these cases, compared with 6.9% otherwise (p < 0.001) . The rate of unnecessary prescribing was 5.1% when the physician estimate differed from the true probability of a group A streptococcal infection by <10%, 16.0% for an error of 10-29%, 35.6% for an error of 30-49%, and 78.3% when the chance of the infection was overestimated by 50% or more . Clinical error in estimating the likelihood of group A streptococcal infection probably contributes to unnecessary antibiotic use in patients with sore throat.

Eur Arch Otorhinolaryngol, 1999, 256(10), 506 - 9
A fatal case of craniofacial necrotizing fasciitis; Beerens AJ et al.; A case of fatal craniofacial necrotizing fasciitis is described in a 72-year-old diabetic woman and management is discussed . Progressive infection of the eyelids occurred with involvement of the right side of the face . Computed tomography revealed soft tissue swelling . Antibiotic treatment was started and debridement performed; histopathology showed acute inflammation and thrombosis of the epidermis and dermis . Despite treatment, scepticemia occurred, resulting in death less than 48 h after presentation . At this time extensive necrosis had developed in the superficial fascia with undermining and gangrene of surrounding tissues . Streptococcus and Staphylococcus were the pathogens involved . Poor prognosis in similar patients has been associated with extensive infection, involvement of the lower face and neck, delayed treatment, advanced age, diabetes and vascular disease.

Minerva Chir, 1999 Nov, 54(11), 819 - 23
{Necrotizing fasciitis . A diagnostic and therapeutic challenge}; Ciccone G et al.; A case of necrotizing fasciitis of the upper limb caused by group A streptococcal infection and a case with an abscess of the hand caused by staphylococcus aureus, are presented . The anatomo-pathological and clinical differences between the two different types of infection are underlined and stress is laid on the excruciating pain, the high temperature and the rapidly spreading inflammatory-necrotizing evolution of the first case . More than the anatomo-pathological findings of a necrotic area the authors consider more important, the rapidity and the severity of the infection, that can evolve into a toxic shock-like syndrome, and the microbiological isolation of the streptococcus type A . On the basis of personal experience and of an accurate review of the literature, a therapeutical protocol is proposed based on an aggressive surgical approach, prompt specific antibiotic treatment and daily control of the lesions.

J Microbiol Immunol Infect, 1999 Sep, 32(3), 179 - 86
Penicillin-nonsusceptible Streptococcus pneumoniae infections in children; Lu CY et al.; The emergence of penicillin-nonsusceptible Streptococcus pneumoniae (PNSSP) has brought a new clinical challenge . In Taiwan, reports of the prevalence and clinical features of PNSSP infections in children are limited . This study reviewed the resistance patterns of all clinical isolates of S . pneumoniae obtained from patients under 17 years of age from January 1993 through July 1998 in a medical center . Their clinical features and treatment responses were analyzed, with special attention paid to those patients with invasive PNSSP infections . Totally, 170 clinical isolates of S . pneumoniae were obtained from 168 patients aged under 17 years . Among those infections, there were 56 sinusitis (including 4 sinusitis with bacteremia), 44 pneumonia (including 23 pneumonia with bacteremia or empyema), 23 otitis media (including 5 otitis media with bacteremia), 9 simple bacteremia, 9 conjunctivitis, 8 meningitis, 4 peritonitis, 3 skin infections and the other 14 isolates were colonization . One hundred eleven isolates (65.3%) showed reduced penicillin susceptibility by the disk diffusion method . A trend of increasing percentiles of PRSP was noted: 27.3% (3/11) in 1993, 37.5% (9/24) in 1994, 55.5% (10/18) in 1995, 77.5% (31/40) in 1996, 66.0% (31/47) in 1997, and 87.1% (27/31) in 1998 . Minimum inhibitory concentration (MIC) determinations by the E-test showed some of the isolates were intermediately resistant . Prior antibiotic usage was associated with a higher incidence of PNSSP infections . However, most children responded well to antimicrobial treatment.

Antibiot Khimioter, 1999, 44(10), 28 - 32
{The clinical and economic efficacies of short courses of azithromycin in acute sinusitis}; Karpov OI; A randomized study of a 3-day course of azithromycin therapy (500 mg once daily) vs . a 10-day course of co-amoxiclav therapy (625 mg thrice daily) in patients with acute sinusitis was performed with an account of the GCP criteria . One hundred patients in 2 groups each of 50 persons were enrolled . The estimates of the patient body temperature, headache, pain on palpation in the area of the accessory nasal sinuses, nasal cavity stuffing, nasal discharge nature and the nose mucous membrane appearance were recorded prior to the treatment, in 72 hours and on the 10th-12th and 26th-30th days of the treatment . The microbiological analysis of the punctate from the accessory nasal sinuses was undertaken before the antibiotic therapy and 72 hours after its start . The economic analysis included the cost of the antibiotic therapy course, hospitalization term, medical manipulations and laboratory tests as well as the cost/efficacy index . The frequency of the relapses within 6 months after the cure was estimated in the two groups compared . In 72 hours and on the 10th-12th days after the treatment start the efficacy of azithromycin was significantly higher than that of co-amoxiclav . The cure was stated in 41 (82 per cent) and 26 (52 per cent) patients on the 10th-12th days, in 6 (12 per cent) and 21 (42 per cent) patients the improvement was stated and the fail was stated in 3 (6 per cent) and 2 (4 per cent) patients respectively . The efficacy of the drugs on the 26th-30th days after the treatment start did not differ . The isolates of Staphylococcus aureus and Streptococcus pyogenes were the main pathogens . The bacteriologic eradication was recorded in 29 (90.6 per cent) patients treated with azithromycin and only in 18 (69.2 per cent) patients treated with co-amoxiclav . Adverse reactions and relapses of the disease within 6 months after the cure were more frequent in the patients treated with co-amoxiclav . The cost of the azithromycin therapy was significantly lower . It was shown that the shortened course of the azithromycin therapy provided earlier cure of the patients with acute sinusitis, better tolerance of the drug, less frequent adverse reactions, lower cost as compared to the use of co-amoxiclav and no relapses.

J Paediatr Child Health, 1999 Dec, 35(6), 558 - 61
Antibiotic resistance in Streptococcus pneumoniae isolated from children; Nasrin D et al.; OBJECTIVE: To determine the level of antibiotic resistance in pneumoniae (S . pneumoniae) isolated from nasal swabs of healthy children . METHOD: Cross-sectional community survey . SETTING: Survey was undertaken in general practice settings in Canberra during March and April 1998 . SUBJECTS: Four hundred and sixty-one children under 3 years of age enrolled in general practice trial of clinical practice guidelines for antibiotic use . OUTCOME MEASURES: Resistance to penicillin, erythromycin, co-trimoxazole, tetracycline, chloramphenicol and cefotaxime among the isolates of S . pneumoniae . RESULTS: A total of 461 nasal swabs were collected and S . pneumoniae was isolated from 171 (37.1%) . Penicillin resistance was found in 12.3% of these isolates, with high level resistance in 0.6% . Resistance rates were higher for cotrimoxazole (44.4%) and erythromycin (18.1%) than for penicillin . Multidrug resistance was found in 19% of these isolates . There was a significant association between the attendance at a day care centre and carriage of pneumococcus (53% vs 32%, odds ratio (OR) 2.4, 95% confidence interval (CI) 1.5-3.7, P < 0.001) . Children who attended day care centers and had received antibiotics during the 4 months prior to swab collection were three times more likely to carry an antibiotic-resistant isolate than children who had neither attended a day care centre nor received antibiotics (68% vs 40%, OR 3.1, 95% CI 1.2-8.4, P = 0.02) . CONCLUSION: The level of antibiotic resistance in pneumococci from healthy children was of concern . Carriage of pneumococcus was significantly higher in children who attended a day care centre . Resistance was significantly correlated with antibiotic use in combination with day-care attendance . These findings warrant more judicious use of antibiotics in children.

J Bacteriol, 2000 Feb, 182(3), 728 - 33
Ligand-binding properties of the carboxyl-terminal repeat domain of Streptococcus mutans glucan-binding protein A; Haas W et al.; Streptococcus mutans glucan-binding protein A (GbpA) has sequence similarity in its carboxyl-terminal domain with glucosyltransferases (GTFs), the enzymes responsible for catalyzing the synthesis of the glucans to which GbpA and GTFs can bind and which promote S . mutans attachment to and accumulation on the tooth surface . It was predicted that this C-terminal region, comprised of what have been termed YG repeats, represents the GbpA glucan-binding domain (GBD) . In an effort to test this hypothesis and to quantitate the ligand-binding specificities of the GbpA GBD, several fusion proteins were generated and tested by affinity electrophoresis or by precipitation of protein-ligand complexes, allowing the determination of binding constants . It was determined that the 16 YG repeats in GbpA comprise its GBD and that GbpA has a greater affinity for dextran (a water-soluble form of glucan) than for mutan (a water-insoluble form of glucan) . Placement of the GBD at the carboxyl terminus was necessary for maximum glucan binding, and deletion of as few as two YG repeats from either end of the GBD reduced the affinity for dextran by over 10-fold . Interestingly, the binding constant of GbpA for dextran was 34-fold higher than that calculated for the GBDs of two S . mutans GTFs, one of which catalyzes the synthesis of water-soluble glucan and the other of which catalyzes the synthesis of water-insoluble glucan.

J Bacteriol, 2000 Feb, 182(3), 627 - 36
Functional analysis of the small component of the 4-hydroxyphenylacetate 3-monooxygenase of Escherichia coli W: a prototype of a new Flavin:NAD(P)H reductase subfamily; Galan B et al.; Escherichia coli W uses the aromatic compound 4-hydroxyphenylacetate (4-HPA) as a sole source of carbon and energy for growth . The monooxygenase which converts 4-HPA into 3,4-dihydroxyphenylacetate, the first intermediate of the pathway, consists of two components, HpaB (58.7 kDa) and HpaC (18.6 kDa), encoded by the hpaB and hpaC genes, respectively, that form a single transcription unit . Overproduction of the small HpaC component in E . coli K-12 cells has facilitated the purification of the protein, which was revealed to be a homodimer that catalyzes the reduction of free flavins by NADH in preference to NADPH . Subsequently, the reduced flavins diffuse to the large HpaB component or to other electron acceptors such as cytochrome c and ferric ion . Amino acid sequence comparisons revealed that the HpaC reductase could be considered the prototype of a new subfamily of flavin:NAD(P)H reductases . The construction of a fusion protein between the large HpaB oxygenase component and the choline-binding domain of the major autolysin of Streptococcus pneumoniae allowed us to develop a rapid method to efficiently purify this highly unstable enzyme as a chimeric CH-HpaB protein, which exhibited a 4-HPA hydroxylating activity only when it was supplemented with the HpaC reductase . These results suggest the 4-HPA 3-monooxygenase of E . coli W as a representative member of a novel two-component flavin-diffusible monooxygenase (TC-FDM) family . Relevant features on the evolution and structure-function relationships of these TC-FDM proteins are discussed.

J Chemother, 1999 Oct, 11(5), 345 - 8
Does the degree of penicillin susceptibility of Streptococcus pneumoniae affect the bactericidal activity of co-amoxiclav versus oral cephalosporins at physiological concentrations? An in vitro pharmacodynamic simulation; Prieto J et al.; An in vitro model simulating amoxicillin-clavulanic acid (co-amoxiclav) versus oral cephalosporin serum concentrations was used to explore activity over time against penicillin-susceptible and non-susceptible Streptococcus pneumoniae . Initial inoculum reduction > 4 log cfu/ml (>99.9%) was obtained with co-amoxiclav against both strains . Cefuroxime, cefpodoxime and cefaclor achieved a similar reduction against the susceptible strain, but no reduction against the non-susceptible strain.

Arch Intern Med, 2000 Jan 10, 160(1), 89 - 94
Invasive pneumococcal infection in Baltimore, Md: implications for immunization policy; Harrison LH et al.; BACKGROUND: Streptococcus pneumoniae is a leading cause of infectious morbidity and mortality . Although blacks are known to have a higher incidence of invasive pneumococcal infection than whites, detailed analyses of these differences and their implications for vaccine prevention have not been reported . OBJECTIVE: To describe the epidemiological characteristics of invasive pneumococcal infection in Baltimore, Md, and its implications for immunization policy . METHODS: Analysis of active, laboratory-based surveillance during 1995 and 1996 among residents of the Baltimore metropolitan area . RESULTS: Of 1412 cases, 615 patients (43.6%) were classified as white and 766 (54.2%) as black . The annual incidence of invasive pneumococcal infection among white and black residents of the Baltimore metropolitan area was 17.8 and 59.2 per 100000 population, respectively (P<.01) . Among patients aged 18 years and older, the median age of blacks with invasive pneumococcal infections was 27 years younger than that of whites (P<.01) . Among males 40 to 49 years old, blacks had a 12-fold higher average incidence than whites (average incidence, 114.5 and 9.3, respectively; P<.01) . By the age of 65 years, 83.8% of cases had occurred in black adults, as compared with 43.8% in white adults (P<.01) . In a regression model, age, black race, male sex, low median family income, and county prevalence of acquired immunodeficiency syndrome were each independently associated with a higher incidence of pneumococcal infection . CONCLUSIONS: Young urban black adults in the Baltimore metropolitan area have a dramatically higher incidence of invasive pneumococcal infection than whites . The vast majority of cases of invasive pneumococcal infection in blacks occur before age 65 years . Current immunization efforts have not addressed the high incidence of pneumococcal infection in this population.

J Neurol, 1999 Nov, 246(11), 1063 - 8
Streptococcal meningitis: effect of CSF filtration on inflammation and neuronal damage; Schmidt H et al.; The effect of CSF filtration on inflammation and neuronal damage was studied in experimental Streptococcus pneumoniae meningitis . New Zealand white rabbits received either antibiotic therapy alone (ceftriaxone i.v., 20 mg/kg bolus, 10 mg/kg maintenance dose; n = 10) or ceftriaxone plus CSF filtration (n = 11) 12 h after intracisternal infection . Immediately after the onset of antibiotic therapy 300 microliters cisternal CSF was removed, passed through a miniaturized CSF-1 filter at a constant flow of 20 microliters/min, and then reinjected . This procedure was repeated six times at intervals of 20 min . Antibiosis plus CSF filtration caused a transient reduction in CSF bacterial titers and leukocyte counts compared with antibiosis alone (P = 0.04 and 0.02 5 h after initiation of therapy) . CSF lipoteichoic acid concentrations were not reduced . The concentration of neuron-specific enolase in CSF and the density of apoptotic neurons in the dentate gyrus were almost equal 12 h after the onset of treatment . Adjuvant CSF filtration accelerated the elimination of viable bacteria from CSF in comparison to antibiotic treatment alone . Parameters of neuronal destruction, however, were not reduced.

Planta Med, 1999 Dec, 65(8), 747 - 9
Antibacterial hydroxycinnamic esters from Piper caninum from Paluma, north Queensland, Australia . The crystal and molecular structure of (+)-bornyl coumarate; Setzer WN et al.; The crude chloroform bark extract of Piper caninum (Piperaceae) exhibits antibacterial activity against the Gram-positive bacteria, Bacillus cereus, Staphylococcus aureus, and Streptococcus pneumoniae . The antibacterial agents in this extract have been isolated using bioactivity-directed chromatographic techniques and identified by NMR spectroscopy as (+)-bornyl p-coumarate and bornyl caffeate . A single-crystal X-ray structure has been carried out on (+)-bornyl p-coumarate . The compound crystallizes in the orthorhombic space group P2(1)2(1)2(1) (#19) with a = 12.659(4), b = 13.281(4), and c = 10.177(3) A . Fullmatrix least-squares refinement converged at R = 0.047, and Rw = 0.058.

J Basic Microbiol, 1999, 39(5-6), 377 - 80
Antibacterial activity of Orobanche cernua extract; Saadoun I et al.; The effect of the parasitic plant Orobanche cernua extract was evaluated on 5 different Gram-positive and Gram-negative bacteria . Dilution experiments show that the minimum inhibitory concentration (MIC; microgram/ml) of the extract was as follows: Staphylococcus aureus-1526.5; Streptococcus sp.-3125; Streptococcus pyogenes-25,000 and both for Bacillus cereus and Escherichia coli-50,000 micrograms/ml . Data indicated that the MIC of 3125 micrograms/ml is equal to cefotaxime (30 micrograms) and tobromycin (10 micrograms) activity against Streptococcus sp . and S . aureus, respectively; 25,000 and 50,000 micrograms/ml is equal to cefotaxime (30 micrograms) activity against S . pyogenes and B . cereus, respectively, and 50,000 micrograms/ml is equal to nalidixic acid (30 micrograms) activity against E . coli . It can be concluded that the O . cernua extract displays remarkable activity against some Gram-positive bacteria such as Streptococcus and Staphylococcus.

Mayo Clin Proc, 2000 Jan, 75(1), 86 - 97
Antimicrobial therapy for infants and children: guidelines for the inpatient and outpatient practice of pediatriac infectious diseases; Henry NK et al.; In this article, we discuss antimicrobial regimens for both outpatient and inpatient use in infants and children . A substantial number of pediatric patient visits annually result in the prescribing of antimicrobial drugs . The emergence of bacteria resistant to commonly used antimicrobial agents is a growing concern . Information on newer drugs such as meropenem, which is active against penicillin-resistant Streptococcus pneumoniae and gram-negative bacilli, and cefepime, which has activity against gram-negative bacilli including Pseudomonas aeruginosa and against gram-positive cocci is also presented . Management of patients with congenital or acquired immunodeficiencies continues to be challenging in regard to the use of antimicrobial drugs to treat various fungal and viral infections . New formulations of older drugs such as aerosolized tobramycin and amphotericin B lipid complex are available . New antiviral agents have been approved, most of which are antiretroviral agents . Childhood tuberculosis is an ongoing concern, and regimens to treat Mycobacterium tuberculosis in children are discussed.

J Bacteriol, 2000 Jan, 182(2), 448 - 55
Contribution of NADH oxidase to aerobic metabolism of Streptococcus pyogenes; Gibson CM et al.; An understanding of how the heme-deficient gram-positive bacterium Streptococcus pyogenes establishes infections in O(2)-rich environments requires careful analysis of the gene products important in aerobic metabolism . NADH oxidase (NOXase) is a unique flavoprotein of S . pyogenes and other lactic acid bacteria which directly catalyzes the four-electron reduction of O(2) to H(2)O . To elucidate a putative role for this enzyme in aerobic metabolism, NOXase-deficient mutants were constructed by insertional inactivation of the gene that encodes NOXase . Characterization of the resulting mutants revealed that growth in rich medium under low-O(2) conditions was indistinguishable from that of the wild type . However, the mutants were unable to grow under high-O(2) conditions and demonstrated enhanced sensitivity to the superoxide-generating agent paraquat . Mutants cultured in liquid medium under conditions of carbohydrate limitation and high O(2) tension were characterized by an extended lag phase, a reduction in growth, and a greater accumulation of H(2)O(2) in the growth medium compared to the wild-type strain . All of these mutant phenotypes could be overcome by the addition of glucose . Either the addition of catalase to the culture medium of the mutants or the introduction of a heterologous NADH peroxidase into the mutants eliminated the accumulation of H(2)O(2) and rescued the growth defect of the mutants under high-O(2) conditions in carbohydrate-limited liquid medium . Taken together, these data show that NOXase is important for aerobic metabolism and essential in environments high in O(2) with carbohydrate limitation.

J Antimicrob Chemother, 2000 Jan, 45(1), 119 - 21
Macrolide resistance in Belgian Streptococcus pneumoniae; Lagrou K et al.; The genetic basis of macrolide resistance was characterized in 59 Streptococcus pneumoniae isolates . All isolates were collected in 1995 and 1997 and were from invasive infections . The majority of the isolates (54 of 59 isolates) were erythromycin and clindamycin resistant (MLS(B)-phenotype) and carried the ermAM gene . Five isolates were erythromycin resistant but clindamycin susceptible (M-phenotype) . Using PCR the mefE gene was detected in these five isolates . Contrary to the situation found in Canada and the USA, mefE-mediated erythromycin resistance in S . pneumoniae is uncommon in Belgium.

J Antimicrob Chemother, 2000 Jan, 45(1), 49 - 55
Antimicrobial resistance of Streptococcus pneumoniae isolated in Taiwan: an island-wide surveillance study between 1996 and 1997; Fung CP et al.; Between August 1996 and July 1997, 550 clinically significant Streptococcus pneumoniae isolates were collected from 14 geographically separate laboratories in Taiwan . These isolates were serotyped and MICs were determined by agar dilution . Among serotypes covered by the 23-valent vaccine, types 19F, 19A, 23F, 23A and 6B dominated, comprising 255 isolates; among non-vaccine serotypes, types 35, 39, 34, 13 and 31 dominated, comprising 118 isolates . Of the 550 isolates, 310 (56.4%) were resistant to penicillin G (MIC 0 . 12 mg/L), 238 (43.3%) with intermediate resistance (MIC 0.12-1 mg/L) and 72 (13.1%) with high-level resistance (MIC 2 mg/L) . Most non-susceptible pneumococci were of serotypes 19F and 23F; non-susceptible isolates of these serotypes were distributed across all of Taiwan . Fourteen other antibiotics were tested; 83% of the isolates were resistant to tetracycline, 78% to azithromycin, 74% to erythromycin, 54% to clindamycin and 23% to chloramphenicol . Thus, macrolides can no longer be used as first line agents to treat pneumococcal infections in Taiwan . Multi-resistance (isolates resistant to three or more chemically unrelated antibiotics) was found in each serotype or group, but mostly in types 19F and 23F . The emergence of such strains complicates antibiotic selection, but both types are covered by the 23-valent vaccine, as were 82% of the isolates from blood and eight of the nine from cerebrospinal fluid . Good antibiotic control and appropriate use of this vaccine may improve the current problem in Taiwan, especially for the elderly.

J Med Microbiol, 2000 Jan, 49(1), 55 - 62
Haemolytic activity of the Streptococcus milleri group' and relationship between haemolysis restricted to human red blood cells and pathogenicity in S . intermedius; Jacobs JA et al.; A collection of 297 clinically documented 'Streptococcus milleri' strains, identified to the genotype level by 16S rRNA gene hydridisation, was screened for haemolysis of human and animal red blood cells . Forty-nine strains (65%) of the S . intermedius genotype displayed haemolysis restricted to human blood; they were named 'exclusive human haemolytic' (EHH) S . intermedius strains . The 26 remaining S . intermedius strains were named S . intermedius non-EHH strains . Quantitative studies on the haemolysis indicated that intermedilysin was the factor involved . The S . intermedius EHH strains represented the S . intermedius phenotype, whereas the S . intermedius non-EHH strains were phenotypically characteristic of S . constellatus . The complete 16S rRNA sequences of the S . intermedius EHH strains exhibited identity with S . intermedius strains ATCC 27335 (= NCDO 2227, NCTC 11324); the 16S rRNA sequences of the S . intermedius non-EHH strains were identical to S . constellatus strain ATCC 27823 (= NCDO 2226, NCTC 11325) except for positions 228 and 229 that carried an S . intermedius sequence signature . The 16S sequence similarities between the non-EHH strains and the S . constellatus and the S . intermedius type strains were 99.5% and 98.6%, respectively . Hybridisations of the complete 16S rRNA genes with oligonucleotide probes indicated a 16S rRNA homogeneity within the S . intermedius EHH and the non-EHH strains respectively . The S . intermedius EHH strains were isolated most frequently from infection- and abscess-related specimens . The present data emphasise the genetic variability within the S . constellatus species and redefine the S . intermedius species as a homogeneous group at the 16S rRNA level.

Md Med J, 1999 Nov-Dec, 48(6), 292 - 4
A case of post-streptococcal reactive arthritis; Howell EE et al.; Reactive arthritis is a term used to describe a sterile inflammatory arthritis occurring after a documented infection elsewhere in the body . Group A streptococcus is known to cause such an arthropathy in the setting of acute rheumatic fever . Friedberg first postulated that a reactive arthritis might occur in response to a streptococcal pharyngeal infection as a separate entity from rheumatic fever in the 1950s . Then, in the 1980s, other investigators began describing cases of reactive arthritis that were not characteristic of acute rheumatic fever based on certain observations and application of criteria . We present a patient whose clinical features are more consistent with post-streptococcal reactive arthritis than acute rheumatic fever.

Microbiology, 1999 Dec, 145 ( Pt 12), 3477 - 86
Bacterial fibronectin-binding proteins and endothelial cell surface fibronectin mediate adherence of Staphylococcus aureus to resting human endothelial cells; Peacock SJ et al.; Adhesion of Staphylococcus aureus to human endothelial cells is implicated in the pathogenesis of invasive staphylococcal disease . The adhesion to endothelial cells of isogenic mutants defective in defined surface structures was studied . Three strains of S . aureus defective in fibronectin-binding proteins FnBPA and FnBPB showed reduced adhesion . This was fully restored by complementation of a FnBPA- FnBPB- mutant derived from strain 8325-4 with a multicopy plasmid encoding FnBPA or FnBPB . Adhesion of mutants defective in other surface structures was unaffected . Anti-fibronectin antibodies blocked adhesion of 8325-4 to endothelial cells, while adhesion of strains 8325-4, P1 and five clinical isolates was inhibited by the recombinant form of the binding domain of FnBPB (rFNBD) from Streptococcus dysgalactiae . Adherence of bacterial aggregates resulting from the presence of purified fibrinogen was also inhibited by rFNBD protein . Three strains of S . aureus defective in FnBPA and FnBPB were not internalized by endothelial cells . S . aureus FnBPs mediate adhesion to human endothelial cells and are required for subsequent internalization, interactions of potential relevance to pathogenesis and treatment.

J Ethnopharmacol, 1999 Dec 15, 68(1-3), 299 - 306
Potential of the aqueous extract of Terminalia chebula as an anticaries agent; Jagtap AG et al.; The aqueous extract from Terminalia chebula was tested for its ability to inhibit the growth and some physiological functions of Streptococcus mutans . The extract strongly inhibited the growth, sucrose induced adherence and glucan induced aggregation of S . mutans . Mouthrinsing with a 10% solution of the extract inhibited the salivary bacterial count and salivary glycolysis . Mouthrinsing with the extract significantly reduced total bacterial counts and the total streptococcal counts in the saliva samples obtained up to and including 3 h after rinsing, compared with the counts obtained prerinsing or after placebo rinsing . The extract successfully inhibited glycolysis of salivary bacteria for up to 90 min postrinsing.

J Ethnopharmacol, 1999 Dec 15, 68(1-3), 97 - 102
Screening of antibacterial activity of Amaicha del Valle (Tucumán, Argentina) propolis; Nieva Moreno MI et al.; Propolis is extensively used in Argentine folk medicine . Alcoholic extracts of propolis from four localities of Amaicha del Valle (El Paraiso, La Banda Este, La Banda Oeste and El Molino), Province of Tucuman and from Cerrillos, Province of Santiago del Estero, Argentina were prepared . All showed antibacterial activity against Gram positive bacteria, the propolis from La Banda Este being the most active (MIC = 7.8 microg/ml) against Streptococcus piogenes, an antibiotic resistant bacterium . Thin layer chromatographic (TLC) separation profiles of propolis from Amaicha del Valle region were similar but differ from the alcoholic extract of the propolis from Cerrillos, another phytogeographical region of Argentina (provincia chaquena) . Bioautographic assays of the TLC profiles showed that several separated compounds of the Amaicha del Valle propolis have antibacterial activity . The difference in composition between Amaicha del Valle and Cerrillos propolis coincides with a different phytogeographical formation.

Kansenshogaku Zasshi, 1999 Nov, 73(11), 1116 - 22
{Microbiological and clinical studies with Streptococcus pneumoniae isolated in 5 Kitakyushu municipal hospitals}; Ishida M et al.; Epidemiological and microbiological studies were carried out using 200 strains of pneumococci isolated from clinical specimens in 5 Kitakyushu municipal hospitals, between October 1994 and July 1995 . Eighty nine percent of pneumococci were detected in the specimens from the respiratory tract . Pneumococci were isolated mainly from infants under 3-years of age and adults over 50-years of age, and the rates of isolation were 40.5% and 39.5%, respectively . MICs of 8 antimicrobial agents, such as PCG, NFLX, CPFX, LFLX, FLRX, TFLX, SPFX, LVFX, were determined using broth microdilution methods . According to NCCLS standard (1997), recovery rates of PSSP, PISP and PRSP were 48.0%, 39.5% and 12.5%, respectively . Among 7 quinolones, TFLX, SPFX and LVFX were effective so far examined, except for a few resistant strains . Four cases in which quinolones resistant pneumococci were isolated were reviewed retrospectively . Among them 3 cases had been given quinolones before the strains were detected.

South Med J, 1999 Dec, 92(12), 1210 - 2
Pneumococcal abscess manifesting as an anterior mediastinal mass and fatal hemoptysis; Marinella MA; An elderly man had several weeks of night sweats, weight loss, and an anterior mediastinal mass on chest radiography . Computed tomographic-guided needle aspiration was nondiagnostic . Shortly after the patient's admission, three sets of blood cultures yielded Streptococcus pneumoniae . Despite systemic antimicrobials, the patient had an episode of acute hemoptysis and died . Autopsy showed an anterior mediastinal abscess with pneumonic involvement of the left lung . There was histologic evidence of necrotizing pneumonia and parenchymal hemorrhage, which likely resulted in fatal hemoptysis.

Microb Pathog, 2000 Jan, 28(1), 9 - 16
Influence of protein kinase inhibitors on Streptococcus uberis internalization into bovine mammary epithelial cells; Almeida RA et al.; Previous reports indicated that bovine mammary epithelial cells internalized Streptococcus uberis, a bovine mastitis pathogen, and that inhibitors of F-actin microfilament polymerization inhibited bacterial internalization into mammary epithelial cells . In the present report, we show that inhibitors of eukaryotic cell tyrosine protein kinase (TPK) and protein kinase C (PKC), staurosporine, genistein and tyrphostin, significantly reduced internalization of S . uberis into mammary epithelial cells . Short-term treatment (15 min) of mammary epithelial cells with 12- O -tetradecanoylphorbol-13-acetate (TPA), shown previously to up-regulate activity of PKC, significantly increased internalization of S . uberis . Conversely, long-term incubation (24 h) of epithelial cells with TPA, which down-regulates PKC activity, significantly reduced the number of internalized S . uberis . These results suggest that protein kinases (TPK and PKC) are involved in internalization of S . uberis into bovine mammary epithelial cells . Identification of host cell surface receptor(s) and ligands that trigger the uptake signal by S . uberis need to be delineated .

Cytokine, 2000 Jan, 12(1), 26 - 31
Production of cytokines by monocytes, epithelial and endothelial cells activated by Streptococcus bovis; Ellmerich S et al.; There are numerous reports documenting the correlation between Streptococcus bovis bacteraemia and endocarditis in conjunction with colonic diseases . The adherence of S . bovis to either buccal or intestinal epithelial cells seems to be the initial process in colonization and subsequent infection of the host, allowing further adhesion of S . bovis to either endothelial cells or extracellular matrix components which leads to infective endocarditis . Bacterial entry at tumour sites is further assisted by the local action of cytokines that promotes vasodilatation and increased capillary permeability . Thus the ability of S . bovis to adhere to and to stimulate human cells may contribute to the pathogenicity of this bacteria . In the present study, we have shown the ability of S . bovis and wall-extracted antigens (WEA) to adhere to human buccal (KB) or intestinal (Caco-2) epithelial cell lines, to human saphenous vein endothelial cells, to human monocytic cell line (THP-1) and to extracellular matrix components (ECM) (fibronectin, collagen and laminin) . The fixation of S . bovis on cells was followed by the synthesis of IL-8 from all the cells except Caco-2, whereas S . bovis WEA was able to induce cytokine synthesis from all of them, showing the immunomodulatory effect of S . bovis and S . bovis WEA on different cells .

FEMS Microbiol Lett, 2000 Jan 15, 182(2), 237 - 40
Development of molecular methods for identification of Streptococcus bovis from human and ruminal origins; Whitehead TR et al.; Streptococcus bovis has been identified as a causative agent in humans for a variety of diseases, including endocarditis, meningitis, and septicemia . Identification of S . bovis strains of human origin in clinical settings has been problematic due to variations in biochemical tests as compared to ruminal strains of S . bovis, and other streptococcal species . DNA-DNA hybridization with chromosomal DNA from various S . bovis strains indicates that strains of human origin are different from those of ruminal origin . Specific probes have been designed from S . bovis 16S rDNA gene sequences that differentiate strains of human and ruminal origin by direct hybridization and PCR analyses . These techniques now allow for rapid identification of S . bovis strains for clinical and other scientific investigations.

Int J Clin Pract, 1999 Sep, 53(6), 437 - 43
Bacteriological eradication of Streptococcus pneumoniae from patients with acute exacerbations of chronic bronchitis: cefuroxime axetil versus cefixime; Zuck P et al.; The bacteriological eradication rates of Streptococcus pneumoniae from sputum of patients experiencing acute exacerbations of chronic bronchitis (WHO definition) have been compared following therapy with either cefuroxime axetil 250 mg b.d . or cefixime 200 mg b.d . All patients were hospitalised for an acute exacerbation of chronic bronchitis . The study design was a multicentre, double-blind, randomised, parallel group with patients giving written informed consent initially . Patients were recruited to the study if they met the WHO definition of chronic bronchitis, were aged 30-75 years and had a high probability of S . pneumoniae infection based on initial sputum Gram stain . All S . pneumoniae isolates were serotyped and susceptibility tested at the National Reference Centre, Paris . S . pneumoniae was eradicated more rapidly following cefuroxime axetil administration than after cefixime and this difference was statistically significant (p = 0.002) at 2-4 days post-treatment . Clinical endpoints showed a similar trend--94% response to cefuroxime axetil compared with 71% response to cefixime (RR 6.39:1) . Cefuroxime eradicated S . pneumoniae significantly more rapidly than cefixime and patients in the cefuroxime axetil arm had favourable clinical criteria . The data suggest that focused antibacterial studies may be helpful in evaluating antibiotics in acute exacerbation of chronic bronchitis.

Arch Biochem Biophys, 2000 Jan 1, 373(1), 116 - 25
Production and characterization of the functional fragment of pneumococcal surface protein A; Jedrzejas MJ et al.; Pneumococcal surface protein A (PspA) is present on the cell wall of Streptococcus pneumoniae pathogen and has an antigenetically variable N-terminal domain . This aminoterminal domain is essential for full pneumococcal virulence, and monoclonal antibodies raised against it protect mice against pneumococcal infections . We have cloned and expressed a 34-kDa N-terminal fragment of PspA in Escherichia coli in a soluble form using the T7 RNA polymerase pET-20b vector system . Nickel chelate affinity purification followed by size exclusion and anion exchange chromatography yielded large amounts of pure and homogeneous protein . Analytical ultracentrifugation sedimentation velocity band and boundary studies showed that the molecule was present in aqueous solutions in a monomeric form with an axial shape ratio of approximately 1:12, typical of fibrous proteins . Sequence analyses indicated an alpha-helical coiled-coil structure for this monomeric molecule with only few loop-type breaks in helicity . The mostly alpha-helical structure of this PspA construct was consistent with circular dichroism spectroscopy data . Based on the ultracentrifugation studies, the circular dichroism spectra, and the PspA's sequence analyses, two structural models for the amino-terminal part of the PspA molecule are proposed . The evident highly charged and polar character of the surface of the modeled structures suggests functional properties of PspA that are related to the prevention of S . pneumoniae interactions with the host complement system .

Clin Infect Dis, 2000 Jan, 30(1), 191 - 4
Penicillin minimum inhibitory concentration drift in identical sequential Streptococcus pneumoniae isolates from colonized healthy infants; Sisson BA et al.; We monitored the timing of acquisition of nasopharyngeal colonization of Streptococcus pneumoniae in 125 healthy infants during their first 2 years of life . S . pneumoniae was isolated at least once from 59 (47%) of 125 infants aged between 2 and 18 months . Twenty-four infants (19%) were colonized with penicillin-resistant S . pneumoniae at some time during the study . During the course of this investigation, we identified sequential pneumococcal isolates of the same serotype from 5 infants, in which the penicillin minimum inhibitory concentration (MIC) increased over time . For 4 of the 5 infants, sequential isolates were identical, as determined by pulsed-field gel electrophoresis . Sequential S . pneumoniae nasopharyngeal isolates from some healthy infants demonstrated drift in penicillin MIC values over time, from penicillin-susceptible to penicillin-resistant.

Clin Infect Dis, 2000 Jan, 30(1), 157 - 64
Cost-effectiveness of the pneumococcal vaccine in the United States Navy and Marine Corps; Vold Pepper P et al.; Vaccination for Streptococcus pneumoniae has been recommended for its efficacy and cost-effectiveness in elderly and immunocompromised populations . However, its use in active-duty military personnel has not been analyzed . We developed a Markov model to evaluate health and economic outcomes of vaccinating or not vaccinating all members of the active-duty cohort, measuring quality-adjusted life years (QALYs) gained, costs, and marginal cost-effectiveness . Pneumococcal pneumonia vaccination increased each person's life expectancy by 0 . 03 days and decreased costs by $9.88 per person . The magnitude of the benefit of immunization is moderately sensitive to the rate of serious side effects caused by the vaccine, the incidence of pneumonia, the length of protection, and the efficacy of the vaccine . Vaccinating all 575,000 active-duty US Navy and Marine Corps members could save $5.7 million during the time the members are alive and on active duty and could provide a total gain of 54 QALYs . On the basis of these results, the military should consider expanding current guidelines to include pneumococcal vaccine immunization for all active-duty members of the military.

Clin Infect Dis, 2000 Jan, 30(1), 122 - 40
The contribution of specific pneumococcal serogroups to different disease manifestations: implications for conjugate vaccine formulation and use, part II; Hausdorff WP et al.; To assess whether certain serogroups of Streptococcus pneumoniae are preferentially associated with specific disease manifestations, we analyzed all recent pneumococcal disease studies and assessed the relative frequency of isolation of each serogroup by clinical site (as a proxy for different disease states) . In all age groups, serogroups 1 and 14 were more often isolated from blood, and serogroups 6, 10, and 23 were more often isolated from cerebrospinal fluid (CSF); in young children, serogroups 3, 19, and 23 were more often isolated from middle ear fluid (MEF) . Serogroups represented in conjugate vaccines were isolated slightly less frequently from CSF than from blood or MEF . Nonetheless, serogroups in the 9-valent conjugate vaccine formulation still comprised approximately 75% of pneumococcal isolates from the CSF of young children in Europe and in the United States and Canada . These analyses indicate that pneumococcal conjugate vaccines could potentially prevent a substantial proportion of episodes of bacteremic disease, pneumonia, meningitis, and otitis media, especially in young children.

Clin Infect Dis, 2000 Jan, 30(1), 78 - 86
Clonally related penicillin-nonsusceptible Streptococcus pneumoniae serotype 14 from cases of meningitis in Salvador, Brazil; Ko AI et al.; Active hospital-based surveillance in the city of Salvador, Brazil, from December 1995 through October 1998, identified 221 patients with confirmed pneumococcal meningitis . Of these 221 patients, 29 (13%) had isolates with intermediate-level resistance to penicillin . Infection with these penicillin-nonsusceptible isolates was significantly associated with age of <2 years (P<.0019), previous antibiotic use (P<.0006), and coresistance to trimethoprim-sulfamethoxazole (P<.0000) . Serotype 14 was the most prevalent serotype (55.2%) of penicillin-nonsusceptible isolates . Strain typing by repetitive element BOX polymerase chain reaction (PCR) analysis showed that penicillin-nonsusceptible serotype 14 isolates had closely related BOX PCR patterns, whereas penicillin-susceptible serotype 14 isolates each had distinct, unrelated patterns . Penicillin-nonsusceptible serotype 14 isolates from Salvador and other Brazilian cities had similar BOX PCR patterns . These observations indicate that in Brazil a large proportion of cases of penicillin-nonsusceptible pneumococcal meningitis appear to be caused by a closely related group of serotype 14 strains that may have disseminated to widely separate geographic areas.

Clin Infect Dis, 2000 Jan, 30(1), 71 - 7
Clinical outcomes of meningitis caused by Streptococcus pneumoniae in the era of antibiotic resistance; Fiore AE et al.; Limited data are available on clinical outcomes of meningitis due to cefotaxime-nonsusceptible Streptococcus pneumoniae . We analyzed data from 109 cases of pneumococcal meningitis in Atlanta, Baltimore, and San Antonio, which were identified through population-based active surveillance from November 1994 to April 1996 . Pneumococcal isolates from 9% of the cases were resistant to cefotaxime, and isolates from 11% had intermediate susceptibility . Children were more likely to have cephalosporin-nonsusceptible pneumococcal meningitis, but mortality was significantly higher among adults aged 18-64 years . Vancomycin was given upon admission to 29% of patients, and within 48 h of admission to 52% . Nonsusceptibility to cefotaxime was not associated with the following outcomes: increased mortality, prolonged length of hospital or intensive care unit (ICU) stay, requirement of intubation or oxygen, ICU care, discharge to another medical or long-term-care facility, or neurological deficit . Empirical use of vancomycin, current prevalence of drug-resistant S . pneumoniae, and degree of nonsusceptibility to cefotaxime may have influenced these findings.

J Ethnopharmacol, 1999 Nov 1, 67(2), 203 - 12
Anticough and antimicrobial activities of Psidium guajava Linn . leaf extract; Jaiarj P et al.; The anticough activity of Psidium guajava Linn . (guava) leaf extract was evaluated in rats and guinea pigs . The results showed that water extract of the plant at doses of 2 and 5 g/kg, p.o . decreased the frequency of cough induced by capsaicin aerosol by 35 and 54%, respectively, as compared to the control, within 10 min after injection of the extract, (P < 0.01) . However, the anticough activity is less potent than that of 3 mg/kg dextromethorphan which decreased frequency of cough by 78% (P < 0.01) . An experiment on isolated rat tracheal muscle showed that the extract directly stimulated muscle contraction and also synergized with the stimulatory effect of pilocarpine . This effect was antagonized by an atropine . Moreover, growth of Staphylococcus aureus and beta-streptococcus group A, as determined by the disc diffusion method, was inhibited by water, methanol and chloroform extract of dry guava leaves (P < 0.001) . The LD50 of guava leaf extract was more than 5 g/kg, p.o . These results suggest that guava leaf extract is recommended as a cough remedy.

Clin Diagn Lab Immunol, 2000 Jan, 7(1), 49 - 54
An In vitro microbial-caries model used to study the efficacy of antibodies to Streptococcus mutans surface proteins in preventing dental caries; Fontana M et al.; The first step for a pathogenic bacterium to initiate infection is via attachment (i.e., through surface determinants) to a suitable receptor . An in vitro microbial artificial-mouth model was used to test the efficacy of polyclonal antibodies to Streptococcus mutans cell surface proteins (CsAb) and a cell surface 59-kDa protein (59Ab) in preventing S . mutans colonization and carious lesion formation . In study 1, groups of 12 human teeth specimens were inoculated with S . mutans, which were incubated with different concentrations of CsAb (A1 {positive control}, sterile saline, no antibody; A2, 0.007 mg of antibody protein/ml; and A3, 0.7 mg of antibody protein/ml) for 1 h at 37 degrees C . The negative control group (B1) was not infected and was incubated with Trypticase soy broth (TSB) without dextrose supplemented with 5% sucrose (TSBS) . In study 2, the same study design was used except that 59Ab was used instead of CsAb, normal rabbit serum was used in the positive control group (A1), and TSB supplemented with 1% glucose was used as the nutrient to control for sucrose-dependent colonization . All groups were exposed for 4 days to circulating cycles of TSBS and TSB (study 1 and study 2, respectively; 30 min each, three times per day) and a mineral washing solution (21 h per day) . Prior to each nutrient cycle, 1 ml of the appropriate CsAb or 59Ab solution was administered to each group and allowed to mix for 30 min before cycling was resumed . Data obtained by confocal laser scanning microscopy demonstrated the presence of a significantly smaller (P < 0.05) lesion area and a smaller total lesion fluorescence in group A3 than in group A1 for both studies . In study 1, group A2 had significantly smaller values than A1 for lesion depth and area . There were no significant differences between groups A2 and A3 for lesion area or between groups A1 and A2 for total lesion fluorescence . In study 2, there were no significant differences among groups A1 and A2 for lesion depth or between groups A2 and A3 for all of the parameters studied . In both studies, there were no significant differences between S . mutans plaque CFU numbers among any of the groups . These studies demonstrated the efficacy of CsAb and 59Ab in reducing primary caries development in this model, although the underlying mechanism remains unclear.

J Clin Microbiol, 2000 Jan, 38(1), 462 - 3
Streptococcus bovis meningitis in an infant; Grant RJ et al.; Streptococcus bovis is a nonenterococcal, group D streptococcus which has been identified as a causative agent for serious human infections, including endocarditis, bacteremia, and septic arthritis . Several cases of adult S . bovis meningitis have been reported, usually in association with underlying disease . In the neonatal period, it is an uncommon agent of meningitis . We report, to our knowledge, the third documented case of neonatal S . bovis meningitis in the English language literature . As in the previous cases, this neonate showed no anatomical or congenital immunologic lesion which might be expected to predispose the patient to meningitis . Sequencing of the 16S ribosomal DNA gene was performed and a new PCR test was used to secure a more reliable identification of the strain.

J Clin Microbiol, 2000 Jan, 38(1), 458 - 9
Bacteremic pneumonia caused by a single clone of Streptococcus pneumoniae with different optochin susceptibilities; Tsai HY et al.; Two isolates of Streptococcus pneumoniae having different optochin susceptibilities were recovered from a blood sample of a 2-year-old boy with community-acquired pneumonia . The two isolates were documented to belong to a single clone on the basis of the isolates' identical serotype (23F), antibiograms by the E-test, random amplified polymorphic DNA patterns generated by arbitrarily primed PCR, pulsed-field gel electrophoresis, and restriction fragment length polymorphism of the penicillin-binding protein genes pbp2b and pbp2x.

J Clin Microbiol, 2000 Jan, 38(1), 351 - 3
Simplified protocol for pulsed-field gel electrophoresis analysis of Streptococcus pneumoniae; McEllistrem MC et al.; A variety of pulsed-field gel electrophoresis (PFGE) protocols for the molecular subtyping of Streptococcus pneumoniae have been reported; most are time-consuming and complex . We sought to modify reference PFGE protocols to reduce the time required while creating high-quality gels . Only protocol modifications that resulted in high-quality banding patterns were considered . The following protocol components were modified . Lysis enzymes (lysozyme, mutanolysin, and RNase A) were deleted in a stepwise fashion, and then the lysis buffer was deleted . Lysis and digestion were accomplished in a single step with EDTA and N-lauroyl sarcosine (ES; pH 8.5 to 9.3) incubation at 50 degrees C in the absence of proteinase K . All enzymes except the restriction enzyme were omitted . A minimum incubation time of 6 h was required to achieve high-quality gels . All of the reactions were performed within 9 h, and the total protocol time from lysis to gel completion was reduced from 3 days to only 36 h . Combining lysis and digestion into a single step resulted in a substantial reduction in the time required to perform PFGE for S . pneumoniae . The ES solution may have caused cell lysis by activating N-acetylmuramyl-L-alanine amidase, the pneumococcal autolysin.

J Clin Microbiol, 2000 Jan, 38(1), 279 - 81
Importance of inoculum size and sampling effect in rapid antigen detection for diagnosis of Streptococcus pyogenes pharyngitis; Kurtz B et al.; Current recommendations suggest that negative rapid Streptococcus pyogenes antigen tests be backed up with a culture, reflecting evidence that culture may have a higher sensitivity and also that testing of a second swab may yield a different (i.e., a positive) result because of variation in sample size or distribution . If the latter is common, the sensitivities of current antigen detection tests might be improved by simply increasing the amount of sample tested . The present study assessed the effect of antigen testing of two swabs extracted together compared to independent testing of each swab extracted separately for children with clinical pharyngitis . S . pyogenes grew from one or both swabs for 198 (37%) of 537 children . The combined culture was significantly (P < 0.05) more sensitive than culture of either swab alone . Compared to combined culture, antigen testing of two swabs extracted and tested together was significantly more sensitive than two single swab extractions (94.1 versus 80%; P = 0.03); however, the specificity was decreased (81.5 versus 89.8 to 92.7%; P < 0.05) . This study suggests that sample size and/or uneven sample distribution may have influenced the apparent sensitivities of prior studies that compared antigen tests to a single plate culture . A strategy, such as the one used in the present study, that increases the sample size available for antigen testing (i.e., extraction of samples from both swabs) may improve detection rates to a level that will better approximate true disease status and obviate the need for backup cultures if specificity can be improved.

J Clin Microbiol, 2000 Jan, 38(1), 71 - 8
Characterization of Streptococcus agalactiae isolates of bovine and human origin by randomly amplified polymorphic DNA analysis; Martinez G et al.; Streptococcus agalactiae is considered one of the major causes of bovine intramammary infections . It is also found in the vaginas of women without any apparent clinical symptoms, but reports of neonatal infections, causing significant morbidity, are relatively frequent . The aim of this study was to evaluate the genetic diversity of S . agalactiae strains isolated from bovine milk and from asymptomatic women in Quebec, Canada, by randomly amplified polymorphic DNA (RAPD) analysis . A total of 185 bovine isolates and 38 human isolates were first serotyped for capsular polysaccharide by double diffusion in agarose gel (bovine isolates) and coagglutination (human isolates) . Strains were then studied by RAPD using 3 primers, designated OPS11, OPB17, and OPB18, which were selected from 12 primers . Thirty-eight percent of bovine isolates and 82% of human isolates could be serotyped . Prevalent serotypes were type III (28%) for bovine isolates and types V (26%) and III (24%) for human isolates . RAPD results showed that, taken together, all isolates (of bovine and human origin) shared 58% similarity . Ninety-four percent of these isolates were clustered in four groups (I, II, III, and IV) with 70% similarity among them . Three clusters, A (48 isolates), B (14 isolates), and C (32 isolates), with 79 to 80% similarity were identified within group IV, whereas the three other groups did not present any clusters . Despite some clustering of human isolates, relatively high diversity was seen among them . Relatively high heterogeneity was observed with the RAPD profiles, not only for field strains belonging to different serotypes but also for those within a given serotype.

FEMS Immunol Med Microbiol, 2000 Jan, 27(1), 9 - 15
Production, characterization, and application of monoclonal antibodies which distinguish four glucosyltransferases from Streptococcus sobrinus; Nanbu A et al.; A 1,3-alpha-glucan synthase (GTF-I), a highly branched 1, 6-alpha-glucan synthase (GTF-U) and a 1,6-alpha-glucan synthase (GTF-T) were purified to near homogeneity from the culture fluid of Streptococcus sobrinus strain B13N (serotype d) and characterized . In addition, a crude preparation of a recombinant oligo-isomaltosaccharide synthase (rGTF-S) was prepared from a cell-free extract of Escherichia coli MD124 transformant . Using four homogeneous GTF preparations including previously purified rGTF-S as antigens for immunization, 11 murine hybridomas producing a monoclonal antibody (MAb) were established through the fusion of myeloma cells (P3X63-Ag8-U1) and spleen cells of immunized BALB/c mice . When the immunoreactivities of the resultant MAbs were tested, all five MAbs raised against GTF-I, all three MAbs raised against GTF-T, and two of three MAbs raised against GTF-U reacted specifically with the homologous enzyme alone, while one MAb (B86) raised against GTF-U cross-reacted strongly with all GTFs . Although no MAb monospecific for rGTF-S was obtained, precise recognition of GTF-S was possible using the nonspecific B86 antibody together with the MAbs monospecific for the three glucan synthases . Thus, a set of four typical MAbs (B17, B76, B19 and B86) were successfully used for the identification of gene products expressed in 24 previously constructed E . coli phage clones, and the findings suggested that six phage clones might express a gtfU gene encoding GTF-U which has not been hitherto isolated.

Vet Rec, 1999 Nov 27, 145(22), 635 - 9
Effects of dry cow intramammary therapy on quarter infections in the dry period; Hassan Z et al.; Quarter milk samples were taken from 150 cows from three dairy farms in south-east Queensland at drying off, two, four and six weeks after drying off, at calving, and one, two and three weeks after calving . In each of the herds, the cows were randomly allocated to three groups of approximately equal size . One group had all the quarters of all the cows treated at drying off with a dry cow antibiotic infusion containing cloxacillin; the second group was given no treatment, and the third group had selected quarters treated on the basis of their high activity of N-acetyl-beta-D-glucosaminidase at drying off . Dry cow treatment resulted in a marked reduction in the number of infected quarters at two and four weeks after drying off, so that the comprehensively treated group had significantly less infected quarters at these times (P<0.02) . Twelve dinical cases of mastitis were detected two weeks after drying off in the untreated groups, 10 in the untreated quarters of the selectively treated groups, and no cases in the comprehensively treated groups . These cases were due mainly to Streptococcus uberis and Streptococcus dysgalactiae . The number of infected untreated quarters increased markedly between drying off and two weeks later, but in all three groups there was a marked decrease in the number of infected quarters between six weeks after drying off and calving, suggesting that the mammary glands were more able to overcome infections at this time.

Nurse Pract, 1999 Nov, 24(11), 70, 73, 77 - 80 passim
The emerging threat of antimicrobial resistance: strategies for change; Reece SM; An urgent warning has been issued by public health authorities worldwide about the threat of antimicrobial resistance by common community-acquired microorganisms such as Streptococcus pneumoniae . Many provider practices have been implicated in this emerging health threat by engaging in inappropriate prescriptive behaviors: imprecise infection diagnoses, "giving in" to patient requests, limiting time spent with patients, fearing liability, and inadequately controlling infections . Patient-related factors implicated in the health threat include a lack of knowledge about bacterial versus viral illness, insistence on receiving antibiotics, nonadherence to drug regimens, and exposure to resistant organisms . Antimicrobials in the environment and the adaptability of microorganisms are also factors . This article evaluates the factors promoting resistance and provides strategies for reversing the trend.

Appl Environ Microbiol, 2000 Jan, 66(1), 23 - 8
Purification and partial characterization of a murein hydrolase, millericin B, produced by Streptococcus milleri NMSCC 061; Beukes M et al.; Streptococcus milleri NMSCC 061 was screened for antimicrobial substances and shown to produce a bacteriolytic cell wall hydrolase, termed millericin B . The enzyme was purified to homogeneity by a four-step purification procedure that consisted of ammonium sulfate precipitation followed by gel filtration, ultrafiltration, and ion-exchange chromatography . The yield following ion-exchange chromatography was 6.4%, with a greater-than-2,000-fold increase in specific activity . The molecular weight of the enzyme was 28,924 as determined by electrospray mass spectrometry . The amino acid sequences of both the N terminus of the enzyme (NH(2) SENDFSLAMVSN) and an internal fragment which was generated by cyanogen bromide cleavage (NH(2) SIQTNAPWGL) were determined by automated Edman degradation . Millericin B displayed a broad spectrum of activity against gram-positive bacteria but was not active against Bacillus subtilis W23 or Escherichia coli ATCC 486 or against the producer strain itself . N-Dinitrophenyl derivatization and hydrazine hydrolysis of free amino and free carboxyl groups liberated from peptidoglycan digested with millericin B followed by thin-layer chromatography showed millericin B to be an endopeptidase with multiple activities . It cleaves the stem peptide at the N terminus of glutamic acid as well as the N terminus of the last residue in the interpeptide cross-link of susceptible strains.

Pediatrics . 2000 Jan;105(1):e13.
Post-varicella epiglottitis and necrotizing fasciitis; Slack CL et al.; Varicella is a nearly ubiquitous acquired childhood disease . Infectious complications of varicella can be life- or limb-threatening . These complications appear 3 to 4 days after the appearance of varicella exanthem and are heralded by fever, pain, and erythema of the overlying skin . Airway complications of varicella are rare, rapidly evolving, and, unfortunately, difficult to visualize . We report a child who presented with a unique combination of varicella-induced airway complications-acute epiglottitis and subsequent necrotizing fasciitis of the head and neck . varicella, epiglottitis, necrotizing fasciitis, group A beta-hemolytic streptococcus, nasopharyngoscopy.

Eur J Clin Microbiol Infect Dis, 1999 Nov, 18(11), 777 - 82
Microbial aetiology of community-acquired pneumonia in hospitalised patients; Socan M et al.; Adult patients hospitalised with community-acquired pneumonia were studied prospectively to determine the microbial aetiology of pneumonia . Between April 1996 and March 1997, blood and sputum samples were collected for culture . Throat swabs were obtained for isolation of viruses and for detection of antigens of Chlamydia pneumoniae, influenza viruses A and B, respiratory syncytial virus and parainfluenza virus . Antibodies against Legionella spp., Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia psittaci, Coxiella burnetii, influenza viruses A and B, respiratory syncytial virus, adenovirus and parainfluenza virus were tested in serum samples . Two hundred eleven patients were included in the study; paired sera were available from 152 patients . Blood culture was positive in 23 (10.9%) patients, Streptococcus pneumoniae being the bacterium isolated most frequently . A fourfold or greater rise or fall in the Chlamydia pneumoniae IgG and/or IgM antibody titre was found in 20 (9.5%) patients and a high antibody titre (> or = 1:512) in the first and/or the second serum sample in 18 (18.5%) patients . Antibodies confirming acute Mycoplasma pneumoniae infection were found in 12 (5.7%) patients, Legionella spp . in six (2.8%), Chlamydia psittaci in two and Coxiella burnetii in one . Three patients had pulmonary tuberculosis . Only two patients had a virus present in the throat swab (adenovirus in one patient and echovirus in the other), and in nine patients, viral antigen was detected . Acute viral infection was confirmed in 51 (24.1%) patients . Bacterial pneumonia was diagnosed in 84 (39.8%) patients, 23 of whom had concurrent viral infection . Acute viral pneumonia without any other identified pathogen was diagnosed in 28 patients . Streptococcus pneumoniae and Chlamydia pneumoniae were the most frequently identified microorganisms.

Eur J Clin Microbiol Infect Dis, 1999 Nov, 18(11), 771 - 6
Epidemiological study of Streptococcus pneumoniae carriers in healthy primary-school children; Lopez B et al.; To obtain information on the Streptococcus pneumoniae carrier state in Spanish children, 332 healthy 6-year-old children from nine primary schools in northern Spain were screened . Thirty-six percent of the children had positive cultures yielding 128 strains . Seventy-one strains belonged to 14 serogroup/serotypes, the most frequent being 19, 23, 3, 24 and 11 . Fifty-seven strains were nontypeable . The identification of strains with equivocal results was confirmed at species level by means of hybridisation with a specific probe, pneumolysin-mediated agglutination and a pathogenicity test in mice . Sixty-four percent of strains showed resistance to penicillin, 22% of these also being resistant to cefotaxime . More than 40% of the strains were resistant to trimethoprim-sulfamethoxazole, tetracycline and erythromycin . Twenty percent of the erythromycin-resistant strains were susceptible to clindamycin . Two strains were resistant to rifampicin and one strain was resistant to ofloxacin . All strains were susceptible to vancomycin . Previous antibiotic administration and having siblings under the age of 2 years correlated with the carriage of pneumococcus . There was no correlation with the carriage of antibiotic-resistant strains, or a record of previous infections, previous hospital admissions or having relatives with chronic respiratory disease.

Genome Res, 1999 Dec, 9(12), 1189 - 97
Regulation of the alpha-galactosidase activity in Streptococcus pneumoniae: characterization of the raffinose utilization system; Rosenow C et al.; A 10.2-kb gene region was identified in the Streptococcus pneumoniae genome sequence that contains eight genes involved in regulation and metabolism of raffinose . The genes rafR and rafS are transcribed as one operon, and their gene products regulate the raffinose-dependent stimulation of a divergently transcribed second promoter (P(A)) directing the expression of aga, the structural gene for alpha-galactosidase . Raffinose-mediated transcription from P(A) results in a 500-fold increase in alpha-galactosidase activity in the cell . A third promoter within the cluster is responsible for the transcription of the remaining five genes (rafE, rafF, rafG, gtfA, and rafX), whose gene products might be involved in transport and metabolism of raffinose . The presence of additional internal promoters cannot be excluded . The aga promoter P(A) is negatively regulated by the presence of sucrose in the growth medium . Consistent with catabolite repression (CR), a DNA sequence with high homology to the CRE (cis-active element) was identified upstream of the aga promoter . Sucrose-mediated CR depends on the phosphoenolpyruvate: sucrose phosphotransferase system (PTS) but is unaffected by a mutation in a gene encoding a homolog of the CRE regulatory protein CcpA.

Presse Med, 1999 Dec 4, 28(38), 2100 - 2
{Pneumococcus: an unusual agent of maternal-fetal infection}; Strobel M et al.; BACKGROUND: Since the advent of antibiotics, Streptococcus pneumoniae has become a very unusual agent of materno-fetal infection . We report two cases . CASE REPORTS: In case n(o) 1, early neonatal meningitis was caused by a penicillin-resistant strain . In case n(o) 2, the mother developed meningitis 16 days after delivery . In both cases, premature rupture of the membranes in otherwise asymptomatic mothers was the initial event and outcome was favorable under amoxicillin alone . The pneumococci were easily recovered fom placental, amniotic and neonatal samples, less easily from the maternal samples . DISCUSSION: The increasing prevalence of penicillin-resistant pneumococci is an emerging problem of real concern . It might increase the very low present incidence of pneumococcal neonatal materno-fetal infection which is a particularly serious infection with up to 60% neonatal mortality . Any type of S . pneumoniae infection, or even colonization, occurring in the peripartum should prompt adequate treatment and suggests considering first line vancomycin for the newborn.

Br J Ophthalmol, 2000 Jan, 84(1), 54 - 9
Corneal ulceration in the elderly in Hyderabad, south India; Kunimoto DY et al.; AIMS: To report demographic, microbiological, therapeutic, anatomical, and visual results of corneal ulceration in the elderly patients seen at a tertiary eye care centre in south India . METHODS: 102 consecutive cases of microbial keratitis in patients 65 years and older were studied . Inclusion criteria were: (i) presence of corneal stromal infiltrate upon slit lamp examination; and (ii) microbiological evaluation of corneal scrapings for suspected microbial keratitis . RESULTS: The principal predisposing factors identified in this study were ocular disease (38.2%), previous ocular surgery in the same eye (29.4%), trauma (17.6%), and severe systemic disease (16.7%) . Contact lens wear was associated with only two cases (2.0%) . 99 organisms were isolated in cultures of corneal scrapings from 74 (72.5%) of the 102 cases . Staphylococcus epidermidis (31.1%), filamentous fungi (25.7%), and Streptococcus pneumoniae (13.5%) were the most common isolates . 12 eyes (11.8%) required surgery, 15 (14.7%) eventually required evisceration, and nine (9.6%) of the 94 followed patients achieved an unaided vision of 20/60 or better at last follow up . CONCLUSIONS: This work represents the largest recent single centre study on (non-viral) microbial keratitis in the elderly, its management, and outcomes of therapy . While the predisposing factors differ from those of general population, the spectrum of microbes responsible for keratitis in the elderly appears to reflect the local microbial flora rather than a predilection for elderly patients . Delay in diagnosis and systemic conditions associated with advancing age probably contribute to poorer outcome from therapeutic measures.

Plasmid, 2000 Jan, 43(1), 85 - 98
Characterization of the gtfB and gtfC promoters from Streptococcus mutans GS-5; Goodman SD et al.; We have characterized the promoter regions of the gtfB and gtfC genes from Streptococcus mutans GS-5 . Using a plasmid-based reporter system, we discovered that the gtfC promoter is an order of magnitude stronger than the gtfB promoter . In addition, we found that a variety of growth conditions failed to affect or discriminate between the expression of the two promoters . Only during the various phases of growth could we demonstrate significant changes in expression . We conclude that gtfB and gtfC promoters are coordinately expressed .

Plasmid, 2000 Jan, 43(1), 49 - 58
A functional lagging strand origin does not stabilize plasmid pMV158 inheritance in Escherichia coli; Hernandez-Arriaga AM et al.; Plasmid rolling circle replication generates single-stranded DNA intermediates . The intracellular amount of these molecules depends upon the efficiency of the conversion of single-stranded into double-stranded plasmid forms, that is, the functionality of the lagging strand origin (sso) . The broad-host-range streptococcal plasmid pMV158 harbors two different ssos, both of which function efficiently in Streptococcus pneumoniae but poorly in Escherichia coli . Plasmid pMV158 is stably inherited in the pneumococcal host, but it is unstable in E . coli . A pMV158 derivative lacking its two ssos is unstable in both strains . We have cloned into this derivative the coliphage f1 lagging strand origin . Whereas the f1 sso was fully functional in E . coli, it did not show any activity in S . pneumoniae, a bacteria closely related to the pMV158 natural host . The presence of the f1 sso did not stabilize pMV158 inheritance in either the gram-positive or the gram-negative host .

Pharmacotherapy, 1999 Sep, 19(9), 1094 - 8
Intravenous immunoglobulin as adjunctive treatment for streptococcal toxic shock syndrome associated with necrotizing fasciitis: case report and review; Cawley MJ et al.; Streptococcal toxic shock syndrome (STSS) is caused by infection with a toxicogenic strain of Streptococcus pyogenes . Clinical manifestations may be those of a mild illness, characterized by malaise, fever, and muscle pain, to severe sepsis and multisystem organ failure . The syndrome may be associated with several invasive infections including necrotizing fasciitis . Treatment is primarily surgical debridement of infected tissue with supportive care, antibiotics, and hemodynamic monitoring . Intravenous immunoglobulin (IVIG) is reported to have beneficial effects in the management of STSS associated with necrotizing fasciitis . The agent was successful in conjunction with surgical excision and antibiotics in a patient with necrotizing fasciitis, toxic shock, and multisystem organ failure . On the basis of this experience and a thorough literature review, we concur that IVIG may be a useful adjunct in the treatment of STSS associated with necrotizing fasciitis.

Dtsch Tierarztl Wochenschr, 1999 Nov, 106(11), 470 - 4
{Effect of puerperal mastitis in primiparous cows on milk production, cell count and culling}; Edinger D et al.; A retrospective cohort study was performed to investigate the effect of clinical mastitis in heifers during the first week post partum (p.p.) on subsequent health and productivity . Primiparous cows that had calved between August 15th, 1996 and August 14th, 1997 (n = 1389) were included in the study . Milk samples were collected from each quarter post partum prior to first milking . The predominant group of bacteria found were Staphylococcus spp . (69%) followed by Streptococcus spp.(12%) and E . coli (5%) . Intramammary infections at calving increased the risk of clinical mastitis within the first week p.p . The cow incidence of mastitis until day 7 p . p . was 38% . Cows were classified into three groups . Group 1: Animals with clinical mastitis prior to calving (n = 35); Group 2: Animals with clinical mastitis between calving and 7 days p . p . (n = 503); Group 3: Animals without mastitis until 7 days p . p . (n = 851) . Mastitis prior to parturition and mastitis within the first week p.p . increased the risk of further cases of mastitis and culling during the first 45 days of lactation . Milk yield of Group 2 was lower and somatic cell counts were higher than in Group 3.

J Infect Dis, 2000 Jan, 181(1), 369 - 73
Isolation and characterization of vancomycin-tolerant Streptococcus pneumoniae from the cerebrospinal fluid of a patient who developed recrudescent meningitis; McCullers JA et al.; The emergence of tolerance to vancomycin has recently been reported in Streptococcus pneumoniae, the most common cause of bacterial meningitis . A vancomycin- and cephalosporin-tolerant strain of S . pneumoniae, the Tupelo strain, was isolated from the cerebrospinal fluid of a patient who then developed recrudescence of meningitis despite treatment with vancomycin and a third-generation cephalosporin . The Tupelo strain evidenced no lysis in the exponential or stationary phase of growth when exposed to vancomycin and only minimal loss of viability . Further characterization revealed normal autolysin expression, localization, and triggering by detergents, indicating that the defect leading to tolerance in the Tupelo strain is in the control pathway for triggering of autolysis . Because tolerance is a precursor phenotype to resistance and may lead to clinical failure of antibiotic therapy, these observations may have important implications for vancomycin use in infections caused by S . pneumoniae.

Pediatr Infect Dis J, 1999 Dec, 18(12), 1096 - 100
Improved outcome of clindamycin compared with beta-lactam antibiotic treatment for invasive Streptococcus pyogenes infection; Zimbelman J et al.; CONTEXT: Animal model studies have demonstrated the failure of penicillin to cure Streptococcus pyogenes myositis and have suggested that clindamycin is a more effective treatment . OBJECTIVE: To determine the most effective antibiotic treatment for invasive S . pyogenes infection in humans . DESIGN AND SETTING: We conducted a retrospective review of the outcomes of all inpatients from 1983 to 1997 treated for invasive S . pyogenes infection at Children's Hospital . PATIENTS: Fifty-six children were included, 37 with initially superficial disease and 19 with deep or multiple tissue infections . MAIN OUTCOME MEASURE: Lack of progression of disease (or improvement) after at least 24 h of treatment . RESULTS: The median number of antibiotic exposures was 3 per patient (range 1 to 6) with clindamycin predominating in 39 of 45 courses of protein synthesis-inhibiting antibiotics and beta-lactams predominating amongst the cell wall-inhibiting antibiotics in 123 of 126 of the remainder . Clindamycin was often used in combination with a beta-lactam antibiotic . Overall there was a 68% failure rate of cell wall-inhibiting antibiotics when used alone . Patients with deep infection were more likely to have a favorable outcome if initial treatment included a protein synthesis-inhibiting antibiotic as compared with exclusive treatment with cell wall-inhibiting antibiotics (83% vs . 14%, P = 0.006) with a similar trend in those with superficial disease (83% vs . 48%, P = 0.07) . For those children initially treated with cell wall-inhibiting antibiotics alone, surgical drainage or debridement increased the probability of favorable outcome in patients with superficial disease (100% vs . 41%, P = 0.04) with a similar trend in a smaller number of deep infections (100% vs . 0%, P = 0.14) . CONCLUSIONS: This retrospective study suggests that clindamycin in combination with a beta-lactam antibiotic (with surgery if indicated) might be the most effective treatment for invasive S . pyogenes infection.

Curr Opin Microbiol, 1999 Dec, 2(6), 588 - 92
Competence for transformation: a matter of taste; Tortosa P et al.; Genetic competence in both Bacillus subtilis and Streptococcus pneumoniae, as well as virulence in Staphylococcus aureus, are regulated by quorum-sensing mechanisms that use two-component signal transduction systems to respond to extracellular peptide pheromones . Recent data indicate that in all three systems closely related strains express markedly different pheromones and polytopic membrane receptor proteins . This polymorphism may function as a sexual isolation mechanism . In B . subtilis the downstream segment of the competence regulatory pathway acts by controlling the stability of a key transcription factor . In S . pneumoniae the downstream segment involves the transcriptional activation of a minor sigma factor that is in turn responsible for the expression of late competence genes.

J Colloid Interface Sci, 1999 Dec 15, 220(2), 410 - 418
Deposition of Oral Bacteria and Polystyrene Particles to Quartz and Dental Enamel in a Parallel Plate and Stagnation Point Flow Chamber; Yang J et al.; The aim of this paper is to determine to what extent (i) deposition of oral bacteria and polystyrene particles, (ii) onto quartz and dental enamel with and without a salivary conditioning film, (iii) in a parallel plate (PP) and stagnation point (SP) flow chamber and at common Peclet numbers are comparable . All three bacterial strains showed different adhesion behaviors, and even Streptococcus mitis BMS, possessing a similar cell surface hydrophobicity as polystyrene particles, did not mimic polystyrene particles in its adhesion behavior, possibly as a result of the more negative zeta potentials of the polystyrene particles . The stationary endpoint adhesion of all strains, including polystyrene particles, was lower in the presence of a salivary conditioning film, while also desorption probabilities under flow were higher in the presence of a conditioning film than in its absence . Deposition onto quartz and enamel surfaces was different, but without a consistent trend valid for all strains and polystyrene particles . It is concluded that differences in experimental results exist, and the process of bacterial deposition to enamel surfaces cannot be modeled by using polystyrene particles and quartz collector surfaces .

Eur J Biochem, 2000 Jan, 267(1), 222 - 7
Characterization of Streptococcus pneumoniae 5-enolpyruvylshikimate 3-phosphate synthase and its activation by univalent cations; Du W et al.; The aroA gene (Escherichia coli nomenclature) encoding 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase from the gram-positive pathogen Streptococcus pneumoniae has been identified, cloned and overexpressed in E . coli, and the enzyme purified to homogeneity . It was shown to catalyze a reversible conversion of shikimate 3-phosphate (S3P) and phosphoenolpyruvate (PEP) to EPSP and inorganic phosphate . Activation by univalent cations was observed in the forward reaction, with NH+4, Rb+ and K+ exerting the greatest effects . Km(PEP) was lowered by increasing {NH+4} and {K+}, whereas Km(S3P) rose with increasing {K+}, but fell with increasing {NH+4} . Increasing {NH+4} and {K+} resulted in an overall increase in kcat . Glyphosate (GLP) was found to be a competitive inhibitor with PEP, but the potency of inhibition was profoundly affected by {NH+4} and {K+} . For example, increasing {NH+4} and {K+} reduced Ki(GLP versus PEP) up to 600-fold . In the reverse reaction, the enzyme catalysis was less sensitive to univalent cations . Our analysis included univalent cation concentrations comparable with those found in bacterial cells . Therefore, the observed effects of these metal ions are more likely to reflect the physiological behavior of EPSP synthase and also add to our understanding of how to inhibit this enzyme in the host organism . As there is a much evidence to suggest that EPSP synthase is essential for bacterial survival, its discovery in the serious gram-positive pathogen S . pneumoniae and its inhibition by GLP indicate its potential as a broad-spectrum antibacterial target.

Chemotherapy, 2000 Jan-Feb, 46(1), 23 - 7
In vitro activity of moxifloxacin compared to other fluoroquinolones against different erythromycin-resistant phenotypes of group A beta-hemolytic streptococcus; Esposito S et al.; The aim of the present study was to evaluate the in vitro activity of moxifloxacin (BAY 12-8039) compared to ciprofloxacin, ofloxacin and sparfloxacin against 156 group A beta-hemolytic Streptococcus strains . Sixty strains were macrolide-, lincosamide- and streptogramin-B-susceptible; 16 strains exhibited a constitutive resistance phenotype; 32 strains exhibited an inducible phenotype, and 48 strains were characterized by the M-type efflux-dependent phenotype . The minimum inhibition concentrations were determined by an agar dilution method according to NCCLS-approved guidelines . Moxifloxacin showed an enhanced activity compared with the other fluoroquinolones against the different macrolide-resistant phenotypes .

Am Surg, 1999 Dec, 65(12), 1156 - 9
The continuing challenge of Fournier's gangrene in the 1990s; Olsofka JN et al.; Fournier's disease is a potentially fatal acute, gangrenous infection of the scrotum, penis, or perineum associated with a synergistic bacterial infection of the subcutaneous fat and superficial fascia . Thrombosis of small subcutaneous arterioles with resultant ischemia contributes to the rapid extension of the infection . During a 12-year period, the clinical and operative records of 14 patients with Fournier's gangrene were analyzed . All patients were treated with broad spectrum antibiotics and serial surgical debridements . Nine patients had polymicrobial isolates from the initial wound culture; two patients had Group A Streptococcus species as the sole isolate . The etiology of the infection was identified in 12 patients . Five patients died for an overall mortality of 38 per cent . The mean age of survivors was 51 years compared with 75 years for nonsurvivors (P<0.05) . The last six patients in this series survived . The mean hospital stay was 29 days . Four patients (31%) had a prior history of diabetes; however, 11 patients (85%) had elevated serum glucose levels (>120 mg/dL) on admission . All patients were hypoalbuminemic on admission . Survivors had an average serum creatinine on admission of 1.28 mg/dL compared with 3.1 mg/dL for nonsurvivors . Although supportive care is required in these patients, the mainstay for treatment of Fournier's gangrene entails an aggressive approach with frequent and extensive soft tissue debridements to control the invasive nature of the infection with delayed wound coverage once the infection has been controlled . Elderly patients with evidence of renal dysfunction on admission have a poor prognosis despite aggressive therapy.

Mutat Res, 1999 Dec 7, 435(3), 233 - 43
Molecular analysis of the Deinococcus radiodurans recA locus and identification of a mutation site in a DNA repair-deficient mutant, rec30; Narumi I et al.; Deinococcus radiodurans strain rec30, which is a DNA damage repair-deficient mutant, has been estimated to be defective in the deinococcal recA gene . To identify the mutation site of strain rec30 and obtain information about the region flanking the gene, a 4.4-kb fragment carrying the wild-type recA gene was sequenced . It was revealed that the recA locus forms a polycistronic operon with the preceding cistrons (orf105a and orf105b) . Predicted amino acid sequences of orf105a and orf105b showed substantial similarity to the competence-damage inducible protein (cinA gene product) from Streptococcus pneumoniae and the 2'-5' RNA ligase from Escherichia coli, respectively . By analyzing polymerase chain reaction (PCR) fragments derived from the genomic DNA of strain rec30, the mutation site in the strain was identified as a single G:C to A:T transition which causes an amino acid substitution at position 224 (Gly to Ser) of the deinococcal RecA protein . Furthermore, we succeeded in expressing both the wild-type and mutant recA genes of D . radiodurans in E . coli without any obvious toxicity or death . The gamma-ray resistance of an E . coli recA1 strain was fully restored by the expression of the wild-type recA gene of D . radiodurans that was cloned in an E . coli vector plasmid . This result is consistent with evidence that RecA proteins from many bacterial species can functionally complement E . coli recA mutants . In contrast with the wild-type gene, the mutant recA gene derived from strain rec30 did not complement E . coli recA1, suggesting that the mutant RecA protein lacks functional activity for recombinational repair.

Jt Comm J Qual Improv, 1999 Dec, 25(12), 630 - 40
Issues in the development, dissemination, and effect of an evidence-based guideline for managing sore throat in adults; Sonnad SS et al.; BACKGROUND: In October 1995 the University of Michigan Healthcare System initiated a program to develop and implement guidelines for primary care in an effort to improve the quality and cost-effectiveness of care for common conditions associated with wide variations in clinical practice . One of these conditions was Group A beta-hemolytic streptococcus (GABHS), present in 5% to 20% of adults complaining of sore throat . METHODS: A draft guideline was developed on the basis of a theoretical model of sore throat management, local data, and research evidence . The guideline was revised to reflect physicians' beliefs and practices regarding sore throat management . Guideline recommendations depended only on the number of clinical signs experienced by the patient and included testing only if it was likely to provide additional information about the probability of GABHS . Data on pre- and postdissemination data on patients presenting with sore throat were collected . RESULTS: When physicians believed testing or antibiotics were unnecessary, only 7% of patients demanded screening and only 6% of patients wanted antibiotics . Physician beliefs about a patient's need for testing agreed with guideline recommendations in 63% of patients both before and after guideline dissemination . DISCUSSION: Disseminating locally modified, evidence-based guidelines may not be sufficient to produce practice changes . If the guideline had been followed, the amount of testing would have been reduced by 17% and the appropriateness of testing improved for 32% of sore throat patients . The results indicate the need for implementation efforts that go beyond presenting evidence, even when that evidence is from both the literature and the local practice setting.

Mol Biol Evol, 1999 Dec, 16(12), 1687 - 95
Extensive variation in the ddl gene of penicillin-resistant Streptococcus pneumoniae results from a hitchhiking effect driven by the penicillin-binding protein 2b gene; Enright MC et al.; An internal fragment of the ddl gene, encoding the cytoplasmic enzyme D-alanyl-D-alanine ligase, was sequenced from 566 isolates of Streptococcus pneumoniae and single isolates of Streptococcus mitis and Streptococcus oralis . The 52 alleles found among the S . pneumoniae isolates fell into two groups . Group A alleles were very uniform in sequence and were present in both penicillin-susceptible and penicillin-resistant pneumococci . Group B alleles were much more diverse and were found only in penicillin-resistant isolates . The Streptococcus oralis and Streptococcus mitis alleles were less diverged from group A alleles than some of the group B pneumococcal alleles, suggesting that the latter alleles contain interspecies recombinational replacements . The ddl gene was located 783 bp downstream of the penicillin-binding protein 2b gene (pbp2b) . Sequencing of the pbp2b-recR-ddl-murF region of three penicillin-resistant pneumococci that had diverged ddl alleles showed that the whole region from pbp2b to ddl (or beyond) was highly diverged (about 8%) compared with the sequences from three penicillin-susceptible isolates . The high levels of diversity in the group B ddl alleles from penicillin-resistant isolates were ascribed to a hitchhiking effect whereby interspecies recombinational exchanges at pbp2b, selected by penicillin usage, often extend into, or through, the ddl gene . The data allow the average size of the interspecies recombinational replacements to be estimated at about 6 kb.

J Otolaryngol, 1999 Dec, 28(6), 325 - 31
Cytotoxic changes in hair cells secondary to pneumococcal middle-ear infection; Cook RD et al.; To determine whether the bacterial toxins associated with otitis media could induce morphologic changes in the organ of Corti, we inoculated the middle-ear cavities of healthy guinea pigs with either Streptococcus pneumoniae or sterile saline and then examined the organ of Corti histologically at 1, 2, and 3 weeks postinoculation . We found that the outer hair cells (OHCs) in the infected ears underwent several changes that were dependent on both the length of time following inoculation and also the position of the OHCs in the cochlea . At 2 weeks postinoculation, 7.0 to 20% of the OHC nuclei from the infected animals became very swollen, with the most significant swelling occurring in the basal turn . At 3 weeks postinoculation, 2.5 to 3.5% of the OHCs were missing in the infected animals, with the most significant loss occurring in the basal and middle turns . These results suggest that bacterial otitis media can produce cytotoxic changes in the cochlea . These changes may be a clinically significant factor in the temporary and permanent sensorineural hearing loss that has been associated with bacterial otitis media.

Infect Immun, 2000 Jan, 68(1), 294 - 302
M-like proteins of Streptococcus dysgalactiae; Vasi J et al.; Streptococcus dysgalactiae is one of the most important bacterial species isolated from bovine mastitis . To identify potential virulence factors of this species we prepared chromosomal DNA from strain 8215 and constructed a phage display library . By affinity selection of the library against fibrinogen (Fg), we isolated and characterized a gene, called demA, encoding a protein with the molecular mass of approximately 58 kDa, called DemA, displaying both plasma protein binding properties and sequence similarities with the M and M-like proteins of other streptococcal species . Purified recombinant DemA protein was found to completely inhibit Fg-binding to cells of S . dysgalactiae . A continued sequence analysis revealed that the demA gene was preceded by an open reading frame (dmgA) coding for a putative protein, called DmgA, with high similarities to the Mga proteins of Streptococcus pyogenes . By additional cloning, the corresponding dmgA and demA genes from another strain, called Epi9, were isolated and analyzed . These genes, called dmgB and demB, respectively, revealed a high degree of similarity to the corresponding genes in strain 8215 . Increased binding of Fg by cells of strain Epi9, grown in an atmosphere with 10% CO(2), was correlated to an enhanced transcription of the demB gene as shown in a Northern blot . Strain 8215 did not respond to CO(2), which could be explained by a nonfunctional dmgA gene due to insertion of an insertion sequence element . Based on sequence similarities of the described proteins to Mga, M, and M-like proteins and the response to elevated level of CO(2), we suggest that the dmg and dem genes are members of a regulon similar to the described mga regulon in S . pyogenes, which encodes several virulence factors in this species.

Infect Immun, 2000 Jan, 68(1), 281 - 7
Comparative analysis of the mucosal adjuvanticity of the type II heat-labile enterotoxins LT-IIa and LT-IIb; Martin M et al.; Cholera toxin (CT) and the heat-labile enterotoxin of Escherichia coli (LT-I) are members of the serogroup I heat-labile enterotoxins (HLT) and can serve as systemic and mucosal adjuvants . However, information is lacking with respect to the structurally related but antigenically distinct serogroup II HLT, LT-IIa and LT-IIb, which have different binding specificities for ganglioside receptors . The purpose of this study was to assess the effectiveness of LT-IIa and LT-IIb as mucosal adjuvants in comparison to the prototypical type I HLT, CT . BALB/c mice were immunized by the intranasal (i.n.) route with the surface protein adhesin AgI/II of Streptococcus mutans alone or supplemented with an adjuvant amount of CT, LT-IIa, or LT-IIb . Antigen-specific antibody responses in saliva, vaginal wash, and plasma were assayed by enzyme-linked immunosorbent assay . Mice given AgI/II with LT-IIa or LT-IIb by the i.n . route had significantly higher mucosal and systemic antibody responses than mice immunized with AgI/II alone . Anti-AgI/II immunoglobulin A (IgA) antibody activity in saliva and vaginal secretions of mice given AgI/II with LT-IIa or LT-IIb was statistically similar in magnitude to that seen in mice given AgI/II and CT . LT-IIb significantly enhanced the number of AgI/II-specific antibody-secreting cells in the draining superficial cervical lymph nodes compared to LT-IIa and CT . LT-IIb and CT induced significantly higher plasma anti-AgI/II IgG titers compared to LT-IIa . When LT-IIb was used as adjuvant, the proportion of plasma IgG2a relative to IgG1 anti-AgI/II antibody was elevated in contrast to the predominance of IgG1 antibodies promoted by AgI/II alone or when CT or LT-IIa was used . In vitro stimulation of AgI/II-specific cells from the superficial lymph nodes and spleen revealed that LT-IIa and LT-IIb induced secretion of interleukin-4 and significantly higher levels of gamma interferon compared to CT . These results demonstrate that the type II HLT LT-IIa and LT-IIb exhibit potent and distinct adjuvant properties for stimulating immune responses to a noncoupled protein immunogen after mucosal immunization.

Infect Immun, 2000 Jan, 68(1), 133 - 40
Additive attenuation of virulence of Streptococcus pneumoniae by mutation of the genes encoding pneumolysin and other putative pneumococcal virulence proteins; Berry AM et al.; Although the polysaccharide capsule of Streptococcus pneumoniae has been recognized as a sine qua non of virulence, much recent attention has focused on the role of pneumococcal proteins in pathogenesis, particularly in view of their potential as vaccine antigens . The individual contributions of pneumolysin (Ply), the major neuraminidase (NanA), autolysin (LytA), hyaluronidase (Hyl), pneumococcal surface protein A (PspA), and choline-binding protein A (CbpA) have been examined by specifically mutagenizing the respective genes in the pneumococcal chromosome and comparing the impact on virulence in a mouse intraperitoneal challenge model . Mutagenesis of either the ply, lytA, or pspA gene in S . pneumoniae D39 significantly reduced virulence, relative to that of the wild-type strain, indicating that the respective gene products contribute to pathogenesis . On the other hand, mutations in nanA, hyl, or cbpA had no significant impact . The virulence of D39 derivatives carrying a ply deletion mutation as well as an insertion-duplication mutation in one of the other genes was also examined . Mutagenesis of either nanA or lytA did not result in an additional attenuation of virulence in the ply deletion background . However, significant additive attenuation in virulence was observed for the strains with ply-hyl, ply-pspA, and ply-cbpA double mutations.

Infect Immun, 2000 Jan, 68(1), 13 - 8
Glycosylation of homologous immunodominant proteins of Ehrlichia chaffeensis and Ehrlichia canis; McBride JW et al.; The glycoprotein genes of Ehrlichia chaffeensis (1,644 bp) and Ehrlichia canis (2,064 bp) encode proteins of 548 to 688 amino acids with predicted molecular masses of only 61 and 73 kDa but with electrophoretic mobilities of 120 kDa (P120) and 140 kDa (P140), respectively . The 120-kDa protein gene of E . chaffeensis contains four identical 240-bp tandem repeat units, and the 140-kDa protein gene of E . canis has 14 nearly identical, tandemly arranged 108-bp repeat units . Conserved serine-rich motifs identified in the repeat units of P120 and P140 were also found in the repeat units of the human granulocytotropic ehrlichiosis agent 130-kDa protein and of the fimbria-associated adhesin protein Fap1 of Streptococcus parasanguis . Nearly the entire (99%) E . chaffeensis P120 gene (1,616 bp), the 14-repeat region (78%) of the E . canis P140 gene (1,620 bp), and a 2-repeat region from the E . chaffeensis P120 gene (520 bp) were expressed in Escherichia coli . The recombinant proteins exhibited molecular masses ranging from 1.6 to 2 times larger than those predicted by the amino acid sequences . Antibodies against the recombinant proteins reacted with E . chaffeensis P120 and E . canis P140, respectively . Carbohydrate was detected on the E . chaffeensis and E . canis recombinant proteins, including the two-repeat polypeptide region of E . chaffeensis P120 . A carbohydrate compositional analysis identified glucose, galactose, and xylose on the recombinant proteins . The presence of only one site for N-linked (Asn-Xaa-Ser/Thr) glycosylation, a lack of effect of N-glycosidase F, the presence of 70 and 126 Ser/Thr glycosylation sites in the repeat regions of P120 and P140, respectively, and a high molar ratio of carbohydrate to protein suggest that the glycans may be O linked.

Emerg Infect Dis, 1999 Nov-Dec, 5(6), 757 - 65
Antimicrobial resistance with Streptococcus pneumoniae in the United States, 1997 98; Doern GV et al.; From November 1997 to April 1998, 1,601 clinical isolates of Streptococcus pneumoniae were obtained from 34 U.S . medical centers . The overall rate of strains showing resistance to penicillin was 29 . 5%, with 17.4% having intermediate resistance . Multidrug resistance, defined as lack of susceptibility to penicillin and at least two other non-ss-lactam classes of antimicrobial drugs, was observed in 16.0% of isolates . Resistance to all 10 ss-lactam drugs examined in this study was directly related to the level of penicillin resistance . Penicillin resistance rates were highest in isolates from middle ear fluid and sinus aspirates of children ambulatory-care settings . Twenty-four of the 34 medical centers in this study had participated in a similar study 3 years before . In 19 of these 24 centers, penicillin resistance rates increased 2.9% to 39.2% . Similar increases were observed with rates of resistance to other antimicrobial drugs.

Spinal Cord, 1999 Dec, 37(12), 866 - 70
Holocord intramedullary abscess: an unusual case with review of literature; Desai KI et al.; STUDY DESIGN: A rare case of a holocord intramedullary abscess with review of literature . OBJECTIVES: Summary of clinical presentation, radiology, microbiology, etiology and management of intramedullary spinal cord abscess . Abscess involving the entire spinal cord is extremely rare and awareness of such an event could avoid delay in evacuation of the absess . METHODS: The incidence, clinical presentation, radiological investigations, treatment and etiology of intramedullary spinal cord abscess in 100 consecutive cases are discussed . RESULTS: Intramedullary spinal cord abscesses are rare . Presently, only five cases of holocord intramedullary abscess are described . In our analysis of 100 cases of intramedullary abscess, a male preponderance was found . The first and the third decades were the most common age groups . Prognosis is poor if treatment is delayed . Contrast-enhanced MRI is the ideal investigation for diagnosis . Prompt surgical drainage of the abscess with appropriate antibiotic therapy is mandatory since the natural course of the disease has a very unfavourable outcome . Staphylococcus and Streptococcus were the most common causative organisms . CONCLUSION: Intramedullary spinal cord abscess along the entire length of spinal cord is rare . A thorough history with precise clinical localisation, a high index of suspicion, contrast-enhanced MRI at appropriate level and prompt surgical drainage with appropriate antibiotic therapy are key to the eventual outcome and prognosis.

Caries Res, 2000 Jan-Feb, 34(1), 94 - 8
Anticaries effect of a component from shiitake (an edible mushroom); Shouji N et al.; The caries-inhibiting effect of the extract from shiitake (Lentinus edodes), the most popular edible mushroom in Japan, was studied both in vitro and in vivo . Shiitake extract showed an inhibitory effect on water-insoluble glucan formation from sucrose by crude glucosyltransferases of Streptococcus mutans JC-2 and Streptococcus sobrinus OMZ-176 . The firmly adherent plaque in the artificial plaque formation test was strongly inhibited by shiitake extract . The reduction of firmly adherent plaque caused an increase in the incidence of non- and loosely adherent plaque and a decrease in total plaque formation . A significantly lower caries score was observed in specific pathogen-free rats infected with S . mutans JC-2 and fed with a cariogenic diet containing 0.25% shiitake extract as compared with controls fed the cariogenic diet without shiitake extract.

J Clin Periodontol, 1999 Dec, 26(12), 784 - 92
Systemic doxycycline administration in the treatment of periodontal infections (II) . Effect on antibiotic resistance of subgingival species; Feres M et al.; The purpose of this investigation was to determine the proportion and prevalence of doxycycline resistant species in subgingival plaque samples taken during and after doxycycline administration . 20 subjects with adult periodontitis were randomly assigned to test (n = 10) or control groups (n = 10) . Saliva samples as well as subgingival plaque samples taken from the distal surface of 6 posterior teeth were collected at baseline . All subjects received full mouth SRP and the test group systemic doxycycline at the dosage of 100 mg/day for 14 days . Saliva samples and plaque samples from the distal surface of 2 randomly selected teeth were taken at 3, 7 and 14 days during and after antibiotic administration . Control subjects were sampled at the same time points . Samples were anaerobically dispersed and serially diluted in PRAS Ringer's solution and plated on enriched Trypticase soy blood agar plates with or without 4 microg/ml doxycycline . After 7 days of anaerobic incubation, colonies were counted on both sets of plates . Microbial growth was washed from the doxycycline-containing media and the species identified using 40 DNA probes and checkerboard DNA-DNA hybridization . Differences in proportions of resistant species between test and control groups were tested for significance at each time point using the Mann Whitney test and over time within each group using the Quade test . The mean % (+/-SEM) of isolates resistant to 4 microg/ml doxycycline in the plaque samples of the test subjects increased from 6+/-2 to 48+/-9% during doxycycline administration, decreasing to 25+/-6% 2 weeks later and 9+/-2% at 90 days . In saliva, the % of resistant isolates rose from 13+/-1% to 81+/-10% during doxycycline administration falling to 46+/-8% 2 weeks later and 22+/-5% at 90 days . The % of resistant isolates did not change significantly in plaque or saliva samples of the control subjects at the same time points . For all subject visits combined, the most prevalent resistant species were: Streptococcus anginosus, Streptococcus oralis, Streptococcus intermedius, Streptococcus sanguis, Streptococcus mitis, Veillonella parvula, Actinomyces gerencseriae, Streptococcus constellatus, Actinomyces naeslundii genospecies 2, Streptococcus gordonii, Eikenella corrodens and Actinomyces naeslundii genospecies 1 . Doxycycline resistant strains of these species were detected in both plaque and saliva samples prior to therapy and in the control group . Despite the finding of increased resistance, approximately 50% of the organisms present at periodontal sites at the end of 14 days of doxycycline administration tested sensitive to the agent.

J Clin Periodontol, 1999 Dec, 26(12), 775 - 83
Systemic doxycycline administration in the treatment of periodontal infections (I) . Effect on the subgingival microbiota; Feres M et al.; Systemic doxycycline is one of the more common antimicrobial agents used in the treatment of periodontal infections and yet little is known of its effect on subgingival plaque composition during and after its administration . The purpose of the present investigation was to evaluate changes in subgingival plaque composition during and after 14 days of doxycycline administration . 20 subjects with adult periodontitis were randomly assigned to test (n = 10) and control (n = 10) groups . The subjects received full mouth clinical assessment of pocket depth, attachment level, BOP, gingival redness, suppuration and plaque accumulation at baseline and 90 days . All subjects received full mouth SRP at baseline and, additionally, the test group received 100 mg doxycycline daily for 14 days . Subgingival plaque samples were taken from the mesial surface of up to 28 teeth in each subject at baseline and 90 days . In addition, plaque samples were taken from 2 randomly selected teeth at 3, 7 and 14 days during and after antibiotic administration . Control subjects were sampled at the same time points . Counts of 40 subgingival species were determined using checkerboard DNA-DNA hybridization and fluorescent detection . Significance of differences between test and control groups was determined at each time point using the Mann Whitney test . Significance of changes over time within test and control groups was determined using the Quade test . A modest but significant reduction in mean pocket depth from baseline to 90 days occurred in both test and control groups . A significant decrease in the % of sites with gingival redness occurred in the test group . There were no significant differences in proportions between test and control groups for 33 of the test species at any time point . Test subjects exhibited lower proportions of 4 Actinomyces species and an increase in 3 Streptococcus species during antibiotic administration . After cessation of doxycycline, Actinomyces sp . increased while Streptococcus sp . returned to baseline proportions . The relationship between these 2 genera appeared to be reciprocal; an increase in one was accompanied by a decrease in the other . Periodontal pathogens including B . forsythus, P . gingivalis, T . denticola and A . actinomycetemcomitans were not significantly altered by oral administration of doxycycline using conventional therapeutic dosage.

J Microbiol Immunol Infect, 1998 Jun, 31(2), 95 - 100
Differential expression of cytokine genes and apoptosis in glioma cell lines upon exposure to bacteria and lipopolysaccharides; Yang BC et al.; The influences of Escherichia coli, Streptococcus pyogenes and lipopolysaccharides (LPSs) on the expression of cytokines and apoptosis were investigated in two glioma cell lines . IL-1beta and TNF-alpha genes were modulated by bacteria in a time dependent fashion and their expression levels varied from sources of bacteria and cell lines used . E . coli and LPSs induced apoptosis in a very limited cell population as judged by cell counts, membrane alternation and DNA break in situ . The expression of fas and IL-6 genes was not affected by bacterial components . In conclusion, aberrant expression of cytokines but not apoptosis may be the major responses of the cells of glial origin upon exposure to bacteria and their components.

Int J Pediatr Otorhinolaryngol, 1999 Oct 15, 50(1), 37 - 43
Where are the receptors for Streptococcus pyogenes located on the tonsillar surface epithelium?
Lilja M, Silvola J, Raisanen S, Stenfors LE.
Streptococcus pyogenes is the most frequent causative agent of acute pharyngotonsillitis (AT) . The first events in the etiopathogenesis of an AT infection caused by these bacterial pathogens are their penetration through the mucus film covering the oropharyngeal mucosa, and their attachment to the surface epithelium . Adherence of S . pyogenes to tonsillar epithelial cells is a precondition for bacterial colonisation, for triggering off cell activation, internalising of bacteria into the epithelial cells and cytokine release from the epithelial cells with subsequent induction of an inflammatory reaction in underlying tissues . Scanning and transmission electron microscopic studies revealed that the surface epithelium of the human palatine tonsils consisted of a weakly keratinized, stratified squamous epithelium built up of pentangular cells where the apical cell surface formed an irregular pattern of microridges . The distance between two adjacent microridges was roughly one-third of the diameter of a S . pyogenes bacterium . By using gold-labelled antiserum to S . pyogenes, we showed that the target region for these pathogens on the epithelial cells during an on-going AT infection was located on the crests of the microridges where bacterial pili made adhesin-receptor contact with the tonsillar surface epithelium.

Immunopharmacology, 1999 Sep, 43(2-3), 103 - 8
Plasma and tissue kallikrein in arthritis and inflammatory bowel disease; Colman RW; To ascertain the participation of the plasma kallikrein-kinin system (KKS) in arthritis and inflammatory bowel disease, we used two rat models resembling rheumatoid arthritis and Crohn's disease . Proteoglycan-polysaccharide from group A streptococcus (PG-APS) produced chronic destructive inflammation and systemic response in the genetically susceptible Lewis rat, in the joints when injected intraperitoneally and in the bowel when injected into the gut wall . In both models, the KKS is activated, as evidenced by decreased prekallikrein, factor XI and high molecular weight kininogen . A specific plasma kallikrein inhibitor, Bz-Pro-Phe-boroarginine, reverses the plasma changes as well as the clinical gross and microscopic pathology of both the experimental arthritis and the inflammatory bowel disease in the genetically susceptible rats . We have also shown that the tissue kallikrein system is involved in the intestinal inflammatory changes . Intestinal tissue kalikrein (ITK) is localized in goblet cells in both normal and inflamed tissue . In chronic granulomatous inflammation, ITK is localized in macrophages . ITK decreases in chronic inflammation, probably due to secretion, since the mRNA is unchanged . Kallikrein binding protein, the ITK inhibitor, decreases due to enzyme-inhibitor complexes . Both plasma and tissue kallikrein are appealing targets for drug therapy of rheumatoid arthritis and Crohn's disease.

Vet Microbiol, 1999 Dec, 70(3-4), 201 - 11
Presence of the Streptococcus suis suilysin gene and expression of MRP and EF correlates with high virulence in Streptococcus suis type 2 isolates; Staats JJ et al.; Nineteen Streptococccus suis type 2 isolates that had been analyzed previously for hemolysin production, ribotype, and virulence in pigs were examined for presence of the gene coding for suilysin by PCR amplification, and southern blot and hybridization techniques . Based on southern blot and hybridization analysis, all isolates tested contained at least a portion of the suilysin gene . PCR amplification of the entire gene resulted in gene fragments from five of the seven highly virulent isolates and none of the moderately virulent or avirulent isolates . Additional PCR analysis showed that mutation or deletions at the 5' end of the suilysin gene in the less virulent isolates prevented amplification of the sly gene fragment from those isolates . The MRP+ (muramidase-released protein) EF+ (extracellular protein) phenotype was also expressed by the same five highly virulent/sly+ isolates.

Drugs, 1999, 58 Suppl 2, 11 - 8
Mechanisms of fluoroquinolone resistance: an update 1994-1998; Piddock LJ; Fluoroquinolone resistance is mediated by target changes (DNA gyrase and/or topoisomerase IV) and/or decreased intracellular accumulation . The genes (gyrA/gyrB/parC/parE) and proteins of DNA topoisomerase IV show great similarity, both at the nucleotide and amino acid sequence level to those of DNA gyrase . It has been shown that there are hotspots, called the quinolone resistance determining region (QRDR), for mutations within gyrA and parC . Based on the Escherichia coli co-ordinates, the hotspots most favoured for giving rise to decreased susceptibility and/or full resistance to quinolones are at serine 83 and aspartate 87 of gyrA, and at serine 79 and aspartate 83 for parC . Few mutations in gyrB or parE/grlB of any bacteria have been described . Efflux of fluoroquinolones is the major cause of decreased accumulation of these agents; for Staphylococcus aureus, the efflux pump involved in norfloxacin resistance is NorA, and for Streptococcus pneumoniae, PmrA . By analysis of minimum inhibitory concentration (MIC) data derived in the presence and absence of the efflux inhibitor reserpine, it has been shown that up to 50% of ciprofloxacin-resistant clinical isolates of S . pneumoniae may possess enhanced efflux . This suggests that efflux may be an important mechanism of clinical resistance in this species . In Pseudomonas aeruginosa, several efflux operons have been demonstrated genetically and biochemically . These operons are encoded by mex (Multiple EffluX) genes: mexAmexB-oprM, mexCD-OprJ system and mexEF-oprN system . The E . coli efflux pump is the acrAB-tolC system . Both the mar operon and the sox operon can give rise to multiple antibiotic resistance . It has been shown that mutations giving rise to increased expression of the transcriptional activators marA and soxS affect the expression of a variety of different genes, including ompF and acrAB . The net result is that expression of OmpF is reduced and much less drug is able to enter the cell; expression of acrAB is increased, enhancing efflux from the cell.

Microbiol Immunol, 1999, 43(9), 905 - 7
Facilitated expansion of pneumococcal colonization from the nose to the lower respiratory tract in mice preinfected with influenza virus; Takase H et al.; A strain of Streptococcus pneumoniae, when inoculated intranasally in 2 microl of suspension into BALB/c mice preinfected with influenza virus, colonized first in the nose, and several days thereafter also colonized significantly in the trachea and lungs with purulent inflammation . Pneumoccocal colonization was also observed in the noses of normal mice after the same bacterial inoculation, but not apparently in the lower respiratory tract . These results suggest that pneumococcal infection may develop from the upper to the lower respiratory tract as a possible sequence preferentially in influenza virus-infected subjects.

J Antimicrob Chemother, 1999 Nov, 44(5), 661 - 7
Comparison of in-vitro pharmacodynamics of once and twice daily ciprofloxacin; Bowker KE et al.; The pharmacodynamics of ciprofloxacin were explored in an in-vitro continuous bacterial culture model of infection, by simulating two oral dosing regimens; 0.5 g 12-hourly (bd) and 1 g 24-hourly (od) . Three strains of Escherichia coli (ciprofloxacin MICs 0.03, 0.5 and 2 mg/L); two strains of Pseudomonas aeruginosa (MICs 0.09 and 1.5 mg/L), two strains of Staphylococcus aureus (MICs 0.12 and 1 mg/L) and two strains of Streptococcus pneumoniae (MICs 0.5 and 2 mg/L) were used . Three pharmacodynamic parameters, T > MIC, C(max)/MIC and AUC/MIC (T = time, C(max) = peak serum concentration, AUC = area under the curve), were compared with area under the bacterial-kill curve (AUBKC) (after transformation of the AUBKC) using a simple E(max) or sigmoidal E(max) model . AUBKC was taken to be the main antibacterial effect measure . The models were compared by inspection of residuals and Akaike information criterion . E(max) models adequately described the relationship between AUC/MIC and AUBKC and between C(max)/MIC and AUBKC, but not between T> MIC and AUBKC . All three pharmacodynamic parameters are related to each other but multiple regression analysis indicated that AUC/MIC was the best individual predictor of AUBKC . Despite this, comparison of od and bd regimens indicates some advantage to od in terms of early antibacterial effect . Serum concentration-time curve shape has some importance in determining antibacterial effect . These data indicate that for ciprofloxacin AUC/MIC ratio is not the sole determinant of antibacterial effect.

J Antimicrob Chemother, 1999 Nov, 44(5), 621 - 7
Activity of moxifloxacin against pathogens with decreased susceptibility to ciprofloxacin; Pong A et al.; A panel of 279 clinical isolates of Gram-positive cocci and Gram-negative bacilli with varying levels of resistance to ciprofloxacin were analysed for susceptibility to moxifloxacin, ciprofloxacin, ofloxacin and nalidixic acid . Moxifloxacin was eight- to 32-fold more potent than ciprofloxacin and ofloxacin against staphylococci and Streptococcus pneumoniae, and equivalent to eight-fold more potent against enterococci . Although ciprofloxacin was intrinsically more potent than the other quinolones against highly susceptible Gram-negative isolates, the percentages of Gram-negative isolates susceptible to 1 mg/L of moxifloxacin or ciprofloxacin, or 2 mg/L of ofloxacin were 78%, 80% and 76%, indicating in-vitro equivalence of the agents against a collection that included isolates with diminished quinolone susceptibility . Staphylococci were analysed according to their ciprofloxacin susceptibility status . As ciprofloxacin resistance increased to high levels, all quinolone MICs increased, but moxifloxacin and ofloxacin MICs increased less than ciprofloxacin MICs . In mutational studies moxifloxacin inhibited more mutants (69%) at a concentration of 1 mg/L than did ciprofloxacin (63%) at 1 mg/L or ofloxacin at 2 mg/L (31%) . The study indicated that moxifloxacin is more potent than ciprofloxacin and ofloxacin against Gram-positive pathogens, may be comparable in activity against less quinolone-susceptible Gram-negative isolates (other than Pseudomonas aeruginosa), and is less affected than ciprofloxacin by mechanisms responsible for increasing quinolone resistance in staphylococci.

Mol Microbiol, 1999 Dec, 34(5), 1070 - 81
Identification of dipeptide repeats and a cell wall sorting signal in the fimbriae-associated adhesin, Fap1, of Streptococcus parasanguis; Wu H et al.; Fap1, a fimbriae-associated protein, is involved in fimbriae assembly and adhesion of Streptococcus parasanguis FW213 (Wu et al., 1998) . In this study, the sequence of the fap1 gene was resolved using a primer island transposition system . Sequence analysis indicated that fap1 was composed of 7659 nucleotides . The predicted Fap1 protein contains an unusually long signal sequence (50 amino acid residues), a cell wall sorting signal and two repeat regions . Repeat regions I and II have a similar dipeptide composition (E/V/I)S, composed of 28 and 1000 repeats respectively . The two regions combined accounted for 80% of the Fap1 coding region . The experimental amino acid composition and isoelectric point (pI) of Fap1 were similar to that predicted from the deduced Fap1 protein . Results of Northern analyses revealed that the fap1 open reading frame (ORF) was transcribed as a 7.8 kb monocistronic message . Insertional inactivation at the 3' end, downstream of the fap1 ORF, did not affect Fap1, fimbrial expression or bacterial adhesion . Insertional inactivation of fap1 immediately upstream of the repeat region II abolished expression of Fap1 and fimbriae, and was concurrent with a diminution in adhesion of FW213 . Inactivation of the cell wall sorting signal of fap1 also eliminated long fimbrial formation and reduced the ability of FW213 to bind to SHA . Fap1 was no longer anchored on the cell surface . Large quantities of truncated Fap1 were found in the growth medium instead . These results suggest that the fap1 ORF alone is sufficient to support Fap1 expression and adhesion, and demonstrate that anchorage of Fap1 on the cell surface is required for long fimbriae formation . These data further document the role of long fimbriae in adhesion of S . parasanguis FW213 to SHA.

Mol Microbiol, 1999 Dec, 34(5), 1018 - 28
The NADH oxidase of Streptococcus pneumoniae: its involvement in competence and virulence; Auzat I et al.; A soluble flavoprotein that reoxidizes NADH and reduces molecular oxygen to water was purified from the facultative anaerobic human pathogen Streptococcus pneumoniae . The nucleotide sequence of nox, the gene which encodes it, has been determined and was characterized at the functional and physiological level . Several nox mutants were obtained by insertion, nonsense or missense mutation . In extracts from these strains, no NADH oxidase activity could be measured, suggesting that a single enzyme encoded by nox, having a C44 in its active site, was utilizing O2 to oxidize NADH in S . pneumoniae . The growth rate and yield of the NADH oxidase-deficient strains were not changed under aerobic or anaerobic conditions, but the efficiency of development of competence for genetic transformation during growth was markedly altered . Conditions that triggered competence induction did not affect the amount of Nox, as measured using Western blotting, indicating that nox does not belong to the competence-regulated genetic network . The decrease in competence efficiency due to the nox mutations was similar to that due to the absence of oxygen in the nox+ strain, suggesting that input of oxygen into the metabolism via NADH oxidase was important for controlling competence development throughout growth . This was not related to regulation of nox expression by O2 . Interestingly, the virulence and persistence in mice of a blood isolate was attenuated by a nox insertion mutation . Global cellular responses of S . pneumoniae, such as competence for genetic exchange or virulence in a mammalian host, could thus be modulated by oxygen via the NADH oxidase activity of the bacteria, although the bacterial energetic metabolism is essentially anaerobic . The enzymatic activity of the NADH oxidase coded by nox was probably involved in transducing the external signal, corresponding to O2 availability, to the cell metabolism and physiology; thus, this enzyme may function as an oxygen sensor . This work establishes, for the first time, the role of O2 in the regulation of pneumococcal transformability and virulence.

Int J Antimicrob Agents, 1999 Oct, 13(2), 137 - 40
Macrolide resistance phenotypes and mechanisms of resistance in Streptococcus pyogenes in La Rioja, Spain; Portillo A et al.; One hundred and thirty seven consecutive clinical Streptococcus pyogenes isolates were evaluated for macrolide-lincosamide-streptogramin resistance (MLS) . Forty of these isolates were resistant to erythromycin (29.2%), 36 of them showed the new M resistance phenotype (erythromycin resistant and clindamycin susceptible) and four isolates had the MLS(B) resistance phenotype (erythromycin and clindamycin resistant) . In all 36 isolates with the M resistance phenotype, the mef gene was identified by polymerase chain reaction (PCR) . In two of the four S . pyogenes isolates with the MLS(B) phenotype, both ermB and ermTR genes were found; negative results were obtained with the other two isolates which might possess a new mechanism of high level resistance against erythromycin not previously described . In summary, a high rate of erythromycin resistance was found in S . pyogenes isolates and the active efflux pump mediated by the mef gene was the mechanism most frequently involved.

Clin Exp Immunol, 1999 Dec, 118(3), 402 - 7
Contribution of serotype-specific IgG concentration, IgG subclasses and relative antibody avidity to opsonophagocytic activity against Streptococcus pneumoniae; Anttila M et al.; The contribution of serotype-specific IgG concentration, subclasses, and avidity to opsonophagocytic activity (OPA) against Streptococcus pneumoniae (Pnc) was evaluated in sera of adults and infants immunized with different pneumococcal vaccines . Antibody concentrations and avidities were measured by enzyme immunoassay (EIA) and OPAs by killing assay of Pnc . The most important factor contributing positively to OPA was the specific IgG level . In infants, a tendency to negative correlation was found between the concentration needed for killing of bacteria and avidity, suggesting that less antibodies of high rather than low avidity were required for killing . No such correlation was seen in adults . However, in adults the avidity was high already before vaccination and the variation was narrow . Thus, avidity was probably not a limiting factor influencing OPA . The effect of IgG2/IgG1 ratio on OPA was mostly negative but insignificant.

Vet Microbiol, 1999 Oct, 70(1-2), 95 - 110
Virulence of Streptococcus canis from canine streptococcal toxic shock syndrome and necrotizing fasciitis; DeWinter LM et al.; The recent recognition of streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis (NF) in dogs caused by Streptococcus canis highlights our lack of knowledge regarding the mechanisms of virulence of this organism . Fifteen isolates of S . canis from cases of canine STSS and/or NF were examined for the presence of 10 Streptococcus pyogenes-associated virulence genes by Southern hybridizations using gene probes generated by PCR . The isolates lacked DNA with homology to eight of the 10 gene probes (speA, speB, speC, mf, ssa, scp, hasA, ska) under low stringency conditions . Thirteen and 15 of 15 isolates hybridized with streptolysin O and M protein gene probes, respectively . Twelve of 15 S . canis isolates were resistant to phagocytosis in canine blood . Electron microscopy revealed the presence of proteinaceous cell surface fibrillae . These results suggest that S . canis possesses M proteins and encodes streptolysin O, but lacks some of the other recognized virulence genes with significant homology to those in S . pyogenes.

J Med Microbiol, 1999 Dec, 48(12), 1107 - 10
High incidence of penicillin resistance amongst clinical isolates of Streptococcus pneumoniae in northern Palestine; Adwan K et al.; One hundred and thirteen consecutive isolates of Streptococcus pneumoniae were collected in Nablus, Palestine between March and Aug . 1997 from children with acute lower respiratory tract infections . Resistance rates were: penicillin 88%, cefuroxime 85%, erythromycin 63%, tetracycline 45%, chloramphenicol 27% and ofloxacin 2% . Resistances to erythromycin and cefuroxime were significantly associated with penicillin resistance . Ofloxacin may be useful against pneumococci resistant to traditional antimicrobial agents . Factors associated with penicillin resistance included hospitalisation and previous use of beta-lactam antibiotics.

J Med Microbiol, 1999 Dec, 48(12), 1103 - 6
Relationship between mutations in parC and gyrA of clinical isolates of Streptococcus pneumoniae and resistance to ciprofloxacin and grepafloxacin; Stewart BA et al.; The mechanisms of resistance to ciprofloxacin and grepafloxacin were studied in 54 clinical isolates of Streptococcus pneumoniae . Restriction fragment length polymorphism analysis following HinfI digestion was used with DNA sequencing to identify mutations in the quinolone resistance-determining regions (QRDRs) of the parC and gyrA genes . Ciprofloxacin MICs up to 16 mg/L were not associated with mutations to these genes in approximately half of the isolates . In other isolates, moderate levels of ciprofloxacin resistance (MIC 8-16mg/L) were associated with an alteration of ParC, most commonly entailing replacement of serine-79 by phenylalanine . High-level ciprofloxacin resistance (MIC 32-128 mg/L) entailed the additional mutation of GyrA with substitution of serine-83 by phenylalanine . Grepafloxacin MICs >4 mg/L were associated with this GyrA mutation alone; no relationship was detected between grepafloxacin MICs and mutation of the QRDR of parC.

Microb Pathog, 1999 Dec, 27(6), 337 - 48
Insertional mutation of orfD of the DCW cluster of Streptococcus pneumoniae attenuates virulence; Palmen R et al.; Mutational analysis of a 5.5 kb fragment of the genome Streptococcus pneumoniae led to the identification of a putative new virulence gene, designated orfD . Insertion mutagenesis of flanking genes on the fragment suggested that the corresponding gene products were required for in vitro growth . In contrast, insertion mutation of orfD did not alter in vitro growth or the transformability pattern of the mutated strain . However, it did reduce bacterial growth in mice and attenuated virulence in an intraperitoneal model of infection . orfD is flanked by orfC (63 codons) and ftsL (105 codons) and all three genes are upstream of pbpx . orfC showed no similarity with other known proteins . ftsL of S . pneumoniae exhibits minimal sequence similarity with ftsL of E . coli, but shares 16% identical residues with the ftsL homologue encoded by ylld of B . subtilis . Also, ftsL of S . pneumoniae has a predicted topology similar to that described for ftsL of E . coli . Putative promoters with an extended -10 box could be identified upstream of both orfC or orfD . The four open reading frames (including pbpx) are orientated in the same direction, and polycistronic transcription could theoretically start at either promoter . Interestingly, this region shows organizational and sequence homologies with genes controlling division and cell wall biosynthesis (DCW) in other bacteria . The attenuation of virulence in the orfD insertion mutant might be due to the loss of function of the orfD gene product or to an altered level of expression of downstream genes .

Clin Infect Dis, 1999 Dec, 29(6), 1450 - 4
Septic arthritis due to Streptococcus pneumoniae in Nottingham, United Kingdom, 1985-1998; Ispahani P et al.; Pneumonia and meningitis are the 2 most frequent manifestations of Streptococcus neumoniae infection . Pneumococcal septic arthritis is considered to be relatively uncommon . Between 1985 and 1998, 32 (8 . 2%) of 389 cases of septic arthritis seen in the 2 hospitals in Nottingham, United Kingdom, were due to S . pneumoniae . Six of 7 children with pneumococcal septic arthritis were aged <2 years . Of the 25 adults, 20 (80%) were aged >60 years, 11 (44%) had concomitant pneumococcal infection elsewhere, and 23 (92%) had articular or nonarticular diseases and/or other risk factors . In the elderly, a lack of febrile response was striking . S . pneumoniae was isolated from blood and joint cultures in >70% of cases, and gram-positive diplococci were seen in the joint fluids of 90% of patients . The mean duration of antimicrobial therapy for adults was twice as long as that for children . Eight (32%) of the adults died.

Clin Infect Dis, 1999 Oct, 29(4), 929 - 31
Group A beta-hemolytic streptococcus meningitis: clinical and microbiological features of nine cases; Sommer R et al.; Group A beta-hemolytic streptococcus (GAS) meningitis is a rare disease in adults . We conducted a retrospective study to describe clinical and microbiological features of nine cases of GAS meningitis in Switzerland . Of nine patients, six had neurosurgical conditions, and five had upper respiratory tract infections . Eight cases were community-acquired . The outcome of GAS meningitis was favorable; only one patient died of neurosurgical complications . No patient presented with toxic shock syndrome . Serotyping failed to reveal a dominant strain, and genotyping revealed that two strains carried the gene encoding the streptococcal pyrogenic exotoxin C and that one strain carried the gene encoding the streptococcal pyrogenic exotoxin A . Our observations suggest that GAS meningitis in adults is associated with neurosurgical conditions and/or an upper respiratory tract infection.

Clin Infect Dis, 1999 Oct, 29(4), 869 - 73
Nationwide survey in Italy of treatment of Streptococcus pyogenes pharyngitis in children: influence of macrolide resistance on clinical and microbiological outcomes . Artemis-Italy Study Group; Varaldo PE et al.; Throat swab specimens were obtained from 3,227 children with symptoms of acute pharyngotonsillitis . After 14 to 21 days, a second throat swab specimen was obtained at a follow-up visit . Over 42% of the 934 strains of Streptococcus pyogenes isolated in the primary study were resistant to erythromycin, azithromycin, and clarithromycin . Eradication rates among the 668 patients who entered the follow-up study were as follows: 84.1%, penicillin recipients; 82.7%, cephalosporin recipients; and 71.7%, macrolide recipients . Among patients treated with macrolides, the eradication rate was approximately 80% when the infecting organisms were erythromycin-susceptible and approximately 60% when they were erythromycin-resistant . These results indicate substantial in vitro macrolide resistance among Italian isolates of S . pyogenes . However, at least for a minor self-limiting condition such as acute S . pyogenes pharyngitis, our findings point to a limited overall correlation between in vitro susceptibility (to penicillins, cephalosporins, or macrolides) and eradication in patients treated with these drugs and an even weaker correlation between in vitro resistance (to macrolides) and noneradication in patients receiving macrolide therapy.

Microbiology, 1999 Nov, 145 ( Pt 11), 3283 - 93
Population biology of Streptococcus pneumoniae isolated from oropharyngeal carriage and invasive disease; Muller-Graf CD et al.; The population structure of Streptococcus pneumoniae in a sample of 134 carried antibiotic-susceptible isolates, and 53 resistant and susceptible invasive isolates, was examined using a DNA-based version of multilocus enzyme electrophoresis: multilocus restriction typing (MLRT) . This involved RFLP analysis of PCR products generated from nine loci of housekeeping genes located around the pneumococcal chromosome . The combination of alleles at each of the nine loci gave an allelic profile or restriction type (RT) . All carried (throat or nasopharyngeal) isolates from children or adults in Oxford and Manchester, UK, and from an HIV-seropositive cohort in Nairobi, Kenya, showed an epidemic population structure . Twelve carried clonal groups, each with different serotypes, were identified at both locations within the UK . Almost all of the carried clones examined (16/17) were found to possess identical RTs or sequence types (STs) to invasive isolates, indicating that frequently carried clones are also associated with cases of invasive disease . As expected from previous studies, the population of 53 invasive, mainly penicillin-resistant, isolates was also found to be at linkage equilibrium . Serotype switching was identified among 14% of RTs that possessed two or more members, or 5.7% of individual isolates within these RTs . In support of a population structure in which there is frequent recombination, there is also clear evidence that the trpA/B locus within pneumococci has evolved by horizontal gene transfer . A non-serotypable isolate from an HIV-seropositive patient in Kenya was clearly genetically distinct from other strains studied, with unique alleles at eight out of nine loci examined . However, it was initially identified as a pneumococcus by a 16S RNA gene probe (Gen-Probe), optochin susceptibility and the presence of pneumolysin and autolysin.

J Antimicrob Chemother, 1999 Oct, 44(4), 533 - 6
Dual inhibitory activity of sitafloxacin (DU-6859a) against DNA gyrase and topoisomerase IV of Streptococcus pneumoniae; Onodera Y et al.; The in-vitro inhibitory activities of sitafloxacin (DU-6859a) and other quinolones against Streptococcus pneumoniae DNA gyrase and topoisomerase IV were measured . IC50s of levofloxacin, ciprofloxacin, sparfloxacin and tosufloxacin against DNA gyrase were almost three to 12 times higher than those against topoisomerase IV . On the other hand, sitafloxacin showed dual inhibitory activity against both enzymes and its IC50s were the lowest among those of the quinolones tested . These results suggest that sitafloxacin is an effective agent against pneumococcal infections and that the incidence of drug-resistant mutants is low.

J Antimicrob Chemother, 1999 Oct, 44(4), 477 - 81
Protective effect of trovafloxacin, ciprofloxacin and ampicillin against Streptococcus pneumoniae in a murine sepsis model; Lacy MK et al.; Trovafloxacin is a new fluoroquinolone that has potent microbiological activity against the pneumococcus, including penicillin-resistant strains . To evaluate the protective effect of trovafloxacin, ciprofloxacin and ampicillin against penicillin-susceptible, -intermediate and -resistant strains of Streptococcus pneumoniae, an intraperitoneal, immunocompetent mouse model of sepsis was used . The minimum lethal dose (MLD) for each isolate was determined in duplicate . A single sc dose of each antibiotic was administered over a wide range of doses 1 h after the ip inoculation of the test isolate at the MLD . The assessment of the protective dose for 50% of the population (PD50) for each antimicrobial/bacteria combination was performed in triplicate and the PD50 value was calculated at the end of 5 days . Results showed that trovafloxacin provided PD50 values that were significantly lower than those of ciprofloxacin for all isolates . For the penicillin-susceptible and -intermediate isolates, the PD50 values of ampicillin were significantly lower than those for either of the fluoroquinolones studied; however, trovafloxacin was statistically superior to both ciprofloxacin and ampicillin against the penicillin-resistant strain . Therefore, regardless of penicillin susceptibility, trovafloxacin has potent activity against Streptococcus pneumoniae and may be a viable alternative for the treatment of penicillin-resistant isolates.

J Antimicrob Chemother, 1999 Oct, 44(4), 461 - 4
Macrolide resistance mechanisms and expression of phenotypes among Streptococcus pneumoniae circulating in Italy; Marchese A et al.; In Italy, macrolide-resistant pneumococci have been isolated at a rate increasing from 6% in 1993 to 31.7% in 1998 . A collection of 161 erythromycin-resistant Streptococcus pneumoniae recovered between 1993 and 1997 has now been phenotypically and genotypically characterized . Approximately 90% of these microorganisms possessed a constitutive MLS(B) mechanism of resistance . PCR detected ermB and mefE genes in strains showing MLS(B) and M phenotypes, respectively . Using pulsed-field gel electrophoresis of chromosomal DNA, one dominant restriction profile and its variations were detected in 51 S . pneumoniae isolates collected from different locations, indicating the circulation of a clone characterized by the possession of a great ability to spread.

Jpn J Antibiot, 1999 Aug, 52(8), 533 - 40
{In vitro and in vivo activities of cefpodoxime proxetil against penicillin-resistant Streptococcus pneumoniae}; Kawada H et al.; We evaluated in vitro and in vivo activities of cefpodoxime proxetil (CPDX-PR) in comparison with other oral beta-lactams, cefdinir (CFDN), cefditoren pivoxil (CDTR-PI), and faropenem (FRPM), against penicillin-susceptible and -resistant Streptococcus pneumoniae . In vitro activities (MICs) of CPDX, CFDN, CDTR, and FRPM against clinical isolates, penicillin-susceptible S . pneumoniae (PSSP: MIC of penicillin G, < or = 0.063 microgram/ml), penicillin-intermediate S . pneumoniae (PISP: MIC of penicillin G, 0.125-1 microgram/ml), and penicillin-resistant S . pneumoniae (PRSP: MIC of penicillin G, > or = 2 micrograms/ml), were tested by an agar dilution method . The MIC80s of CPDX against 27 PSSP strains, 23 PISP strains, and 23 PRSP strains were 0.032, 1, and 8 micrograms/ml, respectively, which were superior to or equal to those of CFDN (0.063, 4, and 8 micrograms/ml) and were inferior to those of CDTR (0.016, 0.5, and 1 microgram/ml) and FRPM (< or = 0.008, 0.25, and 1 microgram/ml) . Infection was induced in mice by inoculating with a PRSP clinical isolate, 9605 or 9601 (serotype 6), or 10692 (serotype 19), through the nares of male ddY mice into the lungs . The mice were treated with drugs with doses of 2-50 mg/kg at 18, 26, 42, and 50 hours after the infection . Viable cell numbers in the lungs and blood were assayed at 66 hours after the infection . The efficacy of each drug was dose-dependent . CPDX-PR showed the most potent in vivo efficacy among the drugs tested against the infections caused by the PRSP strains . MICs of the drugs against PRSP 9605, 9601, and 10692 were as follows: CPDX, 4, 4 and 2 micrograms/ml; CFDN, 16, 16, and 4 micrograms/ml; CDTR, 1, 1, and 0.5 microgram/ml; and FRPM, 1, 0.5, and 0.5 microgram/ml, respectively . Thus, CPDX-PR showed a stronger in vivo activity than that expected from the MICs of CPDX . This was probably caused by the pharmacokinetic advantage of CPDX over the other drugs used in this study.

Acta Otolaryngol, 1999, 119(6), 718 - 23
SIgA- and IgG-coated Streptococcus pyogenes on the tonsillar surfaces during acute tonsillitis; Lilja M et al.; Bacterial swabs were collected from the tonsillar surfaces of eight patients with current acute tonsillitis, culture-positive for Streptococcus pyogenes . Using gold-labelled antiserum to S . pyogenes, these micro-organisms could be localized in the samples by transmission electron microscopy . S . pyogenes pathogens were further characterized with gold-labelled antiserum to human IgG and SIgA antibodies . Roughly 90% of the pathogens were found coated with IgG antibodies, irrespective of the duration of the disease, whereas the proportion of SIgA-coated pathogens increased with disease duration . Insufficient IgA coating of pathogens might well be a contributory cause of the induction of tonsillar infection, probably due to inadequate prevention of the attachment of the S . pyogenes bacteria to the tonsillar surface epithelium.

Pediatrics, 1999 Dec, 104(6), 1394 - 6
Resolution of HIV-associated nephrotic syndrome with highly active antiretroviral therapy delivered by gastrostomy tube; Viani RM et al.; There is no consensus regarding the specific management of HIV-associated nephrotic syndrome . We report a child whose first manifestation of human immunodeficiency virus type 1 (HIV-1) infection was nephropathy and wasting syndrome associated with profound immunodeficiency . The patient had a dramatic clinical and immunologic response to triple antiretroviral therapy delivered through a gastrostomy tube, with complete resolution of nephrotic syndrome . A 51/2-year-old African-American girl presented with a 2-week history of cough, chest pain, vomiting, loose stools, abdominal distention, anorexia, and fever . In addition, she had recurrent oral thrush . Her weight and height were below the 5th percentile . She was chronically ill, appearing with oropharyngeal thrush and pitting edema in lower extremities . She had scattered rhonchi and decreased breath sounds on both lung bases . Her abdomen was distended and diffusely tender . A chest radiograph showed consolidation of the right upper and left lower lobes with bilateral pleural effusion . Admission laboratories were consistent with nephrotic syndrome . Streptococcus pneumoniae grew from the blood culture and the child responded well to treatment with intravenous ceftriaxone . She was found to be HIV-infected, her CD4(+) cell count was 3 cells/mcL and her plasma HIV-1 RNA was >750 000 copies/mL . A percutaneous gastrostomy tube was placed for supplemental nutrition . She was treated with stavudine, lamivudine, and nelfinavir via gastrostomy tube with good clinical response . Twenty-one months after instituting antiretroviral therapy, her weight and height had increased to the 50th and 10th percentile respectively, and she had complete resolution of her nephrotic syndrome . Her CD4(+) cell count increased to 1116 cells/mcL and her viral load has remained undetectable . HIV-1 associated nephrotic syndrome has been described in children with profound immunodeficiency . The course of untreated HIV-associated nephrotic syndrome is rapid progression to renal failure in up to 40% of the children . Regardless of the presence of renal insufficiency, if untreated, it is uniformly fatal . A modest improvement of HIV-1 associated nephrotic syndrome has been observed in patients treated with zidovudine . Steroid and cyclosporine treatment have resulted in improved renal function but long-term use of immunosuppressive therapy has raised concerns about safety . We have described, to our knowledge, the first child with HIV-associated nephrotic syndrome who had a remarkable clinical, immunologic, and virologic response to triple-drug combination therapy given by gastrostomy tube, with complete resolution of proteinuria and normalization of the serum albumin . She also had a striking improvement in weight, height, and quality-of-life . Whether the presence of a gastrostomy tube contributed to the excellent response because of improved compliance is unknown, but warrants systematic evaluation.

Rev Neurol, 1999 Sep 1-15, 29(5), 416 - 24
{Intracranial collections of pus . A review of 100 cases}; Gonzalez-Garcia J et al.; INTRODUCTION: In recent decades, important scientific advances have been made, leading to modification of the diagnosis and the treatment of intracranial collections of pus (ICP) . OBJECTIVES: To analyze the changes in various clinicopathological aspects of ICP during the twenty years studied . PATIENTS AND METHODS: We present a retrospective analysis of 100 cases of ICP diagnosed between 1979 and 1998 in the Hospital General de Galicia . We divided the patients into two groups: A (1979-1988) and B (1989-1998), and analyzed the similarities and differences between them . RESULTS: In these two decades, there was a predominance of men over women (4/1) ENT infections (30/100) and surgical-trauma (25/100) were the commonest causes . The diagnosis was established during the week the symptoms started in 40% of group A and 58.1% of group B . The most frequent site for abscesses was in the frontal lobes (28.5%) and temporal lobes (26.1%) and was closely related to the origin of the infection . Culture was positive in 45% of group A and in 60.3% of group B . The commonest micro-organisms found were Streptococcus (38%) and Staphylococcus (26%) . More anaerobes were observed in the second decade . The most usual surgical treatment was excision (86%) . Mortality was 33.3% in the first decade and 5.4% in the second . CONCLUSION: Technological improvements permit earlier, more reliable radiological and micro-biological diagnosis as well as lower morbi-mortality figures for ICP.

QJM, 1999 Dec, 92(12), 719 - 25
Acute bacterial meningitis in adults: a hospital-based epidemiological study; Tang LM et al.; Bacterial meningitis, a world-wide disease, has to be reviewed periodically because the specific micro-organisms responsible for the infection vary with time, geography and patient age . To determine its incidence and clinical features in Taiwan, we reviewed the microbiological records for cerebrospinal fluid (CSF) and blood cultures, and the medical records of patients with bacterial meningitis admitted between 1981 and mid-1998 . Bacterial micro-organisms were demonstrated in the CSF and/or blood in 395 patients with 418 episodes of bacterial meningitis . Streptococcus species were the most common causative micro-organism group, at 23 . 21% of all episodes . Its prevalence rate significantly decreased from the first 7 years of study (41.9%) to the last 10.5 years (19 . 2%) . However, Klebsiella meningitis and Staphylococcal meningitis were more frequently noted after 1987 . More than 70% of patients had at least one underlying disease or condition . Poor prognostic factors indicated by univariable analysis were: age >60 years; diabetes mellitus; severe neurological deficits on the first day of treatment; infection with Gram-negative bacilli; CSF WBC count >5000x10(6)/l; malignancy; seizure; and bacteraemia . The overall mortality rate was 29.4%, 29.7% in the first 7 years of study and 29 . 4% in the last 10.5 years . The use of new antibiotics has not reduced the mortality rate in our patients with bacterial meningitis.

Antimicrob Agents Chemother, 1999 Dec, 43(12), 3008 - 10
High-level aminoglycoside resistance in the beta-hemolytic group G Streptococcus isolate BM2721; Galimand M et al.; The beta-hemolytic group G Streptococcus clinical isolate BM2721 was resistant to high levels of aminoglycosides by synthesis of AAC(6')-APH(2"), APH(3')-III, and ANT(6) modifying enzymes . The corresponding genes were found to be adjacent as the result of a recombination event between Tn4001 and Tn5405, two transposons originating in staphylococci.

Antimicrob Agents Chemother, 1999 Dec, 43(12), 2998 - 3000
Activity of gemifloxacin against penicillin- and ciprofloxacin-resistant Streptococcus pneumoniae displaying topoisomerase- and efflux-mediated resistance mechanisms; Heaton VJ et al.; Nine penicillin-resistant Streptococcus pneumoniae clinical isolates from Northern Ireland, resistant to ciprofloxacin (MICs, 2 to 64 microg/ml) through topoisomerase- and/or reserpine-sensitive efflux mechanisms, were highly susceptible to gemifloxacin (MICs, 0.03 to 0 . 12 microg/ml) . Two strains (requiring a ciprofloxacin MIC of 64 microg/ml) carried known quinolone resistance mutations in parC, parE, and gyrB, resulting in S79F, D435V, and E474K changes, respectively . Thus, gemifloxacin is active against clinical strains exhibiting altered topoisomerase and efflux phenotypes.

Microbios, 1999, 99(394), 181 - 7
The transfer of bacteria to, and survival on, dental records; Crompton N et al.; The purpose of this study was to ascertain whether viable bacteria could be transferred from gloves to laboratory cards in dental records and, if so, to determine whether bacteria could survive on the paper . The thumbs and forefingers of two types of glove (Biogel D and Microtouch) were inoculated with Streptococcus sanguis and left for various periods of time . A sterile dental laboratory card was then held with the gloves and the number of bacteria surviving on the card determined after various periods of incubation of the card at room temperature . Bacteria were transferred to the laboratory cards and remained viable for up to 72 h . More viable bacteria were transferred from the Microtouch gloves than from the Biogel D gloves, and this was attributable, in part, to the latter gloves exerting a bactericidal effect . The results demonstrated that bacteria can be transferred from gloves to laboratory cards and that these organisms can remain viable for long periods of time . Dental records may, therefore, represent a possible route of cross-infection.






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