Streptococci

Clin Exp Immunol, 2000 Oct, 122(1), 61 - 6
Induction of necrosis and apoptosis of neutrophil granulocytes by Streptococcus pneumoniae; Zysk G et al.; Apoptosis followed by macrophage phagocytosis is the principal mechanism by which neutrophil granulocytes (PMN) are removed from the site of inflammation . To investigate whether Streptococcus pneumoniae causes apoptosis of PMN, we exposed PMN to viable and heat-killed pneumococci and purified pneumococcal cell walls (PCW) . The occurrence of PMN cell death was quantified by flow cytometry using annexin V/propidium iodide labelling of the cells . Intracellular histone-associated DNA fragments were quantified by ELISA . The presence of apoptosis was confirmed by in situ tailing . Exposure of PMN to viable pneumococci caused necrosis of the cells . The pneumococcal cytotoxin pneumolysin, the bacterial production of hydrogen peroxide, and PCW contributed to necrosis . Heat-killed pneumococci accelerated the process of apoptosis observed in cultivated non-stimulated PMN in vitro . These results demonstrated that pneumococci induce PMN cell death . Depending on the intensity of the stimulus, PMN necrosis and apoptosis were observed.

Crit Care Med, 2000 Sep, 28(9), 3249 - 56
Nuclear factor-kappaB activation in mouse lung lavage cells in response to Streptococcus pneumoniae pulmonary infection; Amory-Rivier CF et al.; OBJECTIVES: To assess the state and activation kinetics of the nuclear transcription regulatory protein nuclear factor-kappB (NF-kappaB) in lung lavage cells in a murine pneumococcal pneumonia model and to determine how the virulence of the infecting organisms altered the activation state of NF-kappaB . DESIGN: Experimental, comparative study of three Streptococcus pneumoniae strains that induced three distinct pulmonary diseases . SETTING: Experimental laboratory in a university-based medical center . SUBJECTS: Female BALB/cby mice, 8-10 wks of age . INTERVENTIONS: We randomly divided the mice into the following five groups: a) the control group; b) animals infected by virulent encapsulated S . pneumoniae P4241 strain; c) animals infected by avirulent encapsulated S . pneumoniae P15986 strain; d) animals infected by avirulent unencapsulated S . pneumoniae R6 strain; e) animals infected by virulent lysed S . pneumoniae P4241 strain . Animals were anesthetized and infected by intratracheal delivery of 4 x 10(5) colony-forming units (CFU) of S . pneumoniae per mouse or bacterial components equivalent to 4 x 10(5) CFU for lysed S . pneumoniae challenge . After intratracheal challenge with virulent encapsulated strain P4241, mice developed acute pneumonia, became bacteremic, and died within 3 to 5 days . None of the mice infected with the avirulent encapsulated strain P15986 or the avirulent unencapsulated strain R6 died . After collection of lung lavage cells and nuclear extraction, NF-kappaB activation was determined 1 hr, 4 hrs, 6 hrs and 24 hrs after pneumococcal infection . At the same time, pulmonary and blood clearance, bronchoalveolar lavage cells population, and tumor necrosis factor-alpha production were assessed (six mice per time point) . MEASUREMENTS AND MAIN RESULTS: NF-kappaB was constitutively expressed within nuclear extracts of lung lavage cells from uninfected control mice . A significant increase in NF-kappaB activation was detected within 1 hr after injection of virulent lysed S . pneumoniae P4241 strain (bacterial components equivalent to 4 x 10(5) CFU), and was still present 24 hrs after the injection . After live pneumococcal challenge, significant NF-kappaB activation was detected within 4 hrs with a peak at 24 hrs . Responses to all three strains (P4241, P15986 and R6) were time-dependent (p < .0001), as NF-kappaB activation gradually increased during the first 24 hrs . Moreover, compared with the control uninfected mice, the intensity of the retarded KB oligonucleotide, as determined by densitometry, was increased approximately four- to five-fold and seven-fold in reactions containing nuclear extracts isolated 24 hrs after infection with the avirulent strains P15986 or R6 and the virulent strain P4241, respectively . With the virulent strain P4241, responses were significantly stronger than with the avirulent strains P15986 and R6 (p < .01) . Responses were of similar order with avirulent strains P15986 and R6 (p > .05) . CONCLUSION: Pulmonary infection by S . pneumoniae induced delayed and time-dependent activation of NF-kappaB in mouse lung lavage cells . The degree of NF-kappaB activation in lung lavage cells correlated with the virulence of the infecting organisms . Our results suggest that the more severe the infection, the higher the rise in NF-kappaB.

J Vet Med A Physiol Pathol Clin Med, 2000 Aug, 47(6), 351 - 65
Clinical experiences of treating septic arthritis in the equine by repeated joint lavage: a series of 39 cases; Meijer MC et al.; The condition of septic arthritis was treated in 12 foals with 21 affected joints (Group I) and in 27 adult horses . The adult horses were divided into three groups, based on aetiology of the condition: haematogenous (Group II, n = 6), iatrogenic (Group III, n = 6), and perforating trauma (Group IV, n = 15) . The treatment consisted of an initial systemic antibiotic that anticipated the microbial agents that were considered most likely per group, repeated through-and-through joint lavages every other day and non-steroidal anti-inflammatory drugs . The antibiotics were adjusted to the results of bacteriological culture and susceptibility tests . Joint lavages were continued until the white blood cell count dropped below 15 G/l and bacteriological culture was negative, after which a single dose of a short-acting corticosteroid was administered intra-articularly . Joint recovery rate in group I was 71% . Patient recovery rate of the foals, however, was lower (42%) . Three foals were killed for reasons other than arthritis; one foal because of an arthritis-related problem and three foals because of persistent arthritis . Overall joint recovery rate, equalling patient recovery rate, in the adult horses was 81% . The expected predominance of Streptococcus spp . in haematogenous arthritis in adult horses was not confirmed, indicating that in these cases also, an initial antibiotic treatment with a broad-spectrum combination is preferable . It is concluded that with intensive treatment, the prognosis of septic arthritis in the adult horse can be classified as fair to even good . Results in the foals are not as good, but this seems to be more due to the specific problems surrounding the equine neonate than to unresponsiveness to the treatment.

Comput Med Imaging Graph, 2000 Nov-Dec, 24(6), 407 - 11
A case of Streptococcus pneumoniae meningitis showing a marked contrast enhancement effect of whole arachnoid membrane on MRI; Wanibuchi M et al.; We have experienced the adult case of meningitis caused by the Streptococcus pneumoniae, which showed the most aggressive clinical course . The peculiar and unique magnetic resonance images are reported . The whole arachnoid membrane was prominently enhanced following the contrast material injection, however, no contrast enhancement was observed in subarachnoid space, ependyma, intraventricular cerebrospinal fluid, and dura mater . This implies the superacute phase of the bacterial meningitis, in which inflammation is localized in the whole arachnoid membrane . The contrast enhancement effect in the meningitis may vary depending on the phase and severity, because it is a time-progressive disease.

Biotechnol Bioeng, 2000 Nov 20, 70(4), 363 - 9
Transglycosylation by Streptococcus mutans GS-5 glucosyltransferase-D: acceptor specificity and engineering of reaction conditions; Meulenbeld GH et al.; The acceptor specificity of Streptococcus mutans GS-5 glucosyltransferase-D (GTF-D) was studied, particular the specificity toward non-saccharide compounds . Dihydroxy aromatic compounds like catechol, 4-methylcatechol, and 3-methoxycatechol were glycosylated by GTF-D with a high efficiency . Transglycosylation yields were 65%, 50%, and 75%, respectively, using 40 mM acceptor and 200 mM sucrose as glucosyl donor . 3-Methoxylcatchol was also glycosylated, though at a significantly lower rate . A number of other aromatic compounds such as phenol, 2-hydroxybenzaldehyde, 1,3-dihydroxybenzene, and 1, 2-phenylethanediol were not glycosylated by GTF-D . Consequently GTF-D aromatic acceptors appear to require two adjacent aromatic hydroxyl groups . In order to facilitate the transglycosylation of less water-soluble acceptors the use of various water miscible organic solvents (cosolvents) was studied . The flavonoid catechin was used as a model acceptor . Bis-2-methoxyethyl ether (MEE) was selected as a useful cosolvent . In the presence of 15% (v/v) MEE the specific catechin transglucosylation activity was increased 4-fold due to a 12-fold increase in catechin solubility . MEE (10-30% v/v) could also be used to allow the transglycosylation of catechol, 4-methylcatechol, and 3-methoxycatechol at concentrations (200 mM) otherwise inhibiting GTF-D transglycosylation activity.

Rinsho Biseibutshu Jinsoku Shindan Kenkyukai Shi, 2000 Aug, 11(1), 39 - 45
Basic studies on group B streptococcal (GBS) culture medium; Higashide K et al.; Yeast extract and Serum are said to be necessary for the pigmentation of Group B Streptococcus (hereafter, GBS) . We're examined the necessity of these for the GBS pigmentation . Firstly, we examined the following four types of culture media . (1) The medium in which serum was excluded from the New Granada medium (hereafter, called Basic medium) . (2) New Granada medium (hereafter, S medium) . (3) The medium in which Yeast extract was added to (1) (hereafter, Y medium) . (4) The medium in which added Serum and Yeast extract were added to (1) (hereafter, SY medium) . As for GBS tested (7 serotypes, 27 strains), Basic medium showed the strongest pigmentation potency, but, S and SY medium showed the weakest . About the quickness of pigmentation initiation, similar to the potency above, Basic medium was the quickest, followed by Y medium, and then S medium and SY medium . Among the media examined, there were no differences in the relationships between the quantity of GBS applied and the positive ratio of each media.>From these results, among four types of the media, Basic medium is thought to be the best one for the GBS detection.

Rinsho Biseibutshu Jinsoku Shindan Kenkyukai Shi, 2000 Aug, 11(1), 33 - 7
Preventive procedures against GBS infection by means of antibody measurement; Mikamo H et al.; OBJECTIVE: Screening group B Streptococcus (GBS) in the vagina of pregnant women and measuring serum level of its type-specific antibody would be useful for cost-benefit of the prevention against GBS infection . STUDY DESIGN: The subjects included a total of 1,150 pregnant women who consented to the study . Serotypes of GBS detected were classified with antiserum . Serum type-specific antibody titers were measured by a bacterial agglutination method . RESULTS: Of a total of 1,150 pregnant women, 250 cases (21.7%) had GBS in the vagina . The turn of GBS serotype occurrence was types VI (NT6) (27 . 2%), VIII (JM9) (25.2%), III (11.2%), Ia (8.8%), and Ib (8.0%) . None or low type-specific antibody titer was 41.0% of Ia, 20.0% of Ib, 22 . 0% of II, 15.0% of III, 65.0% of VI, and 69.0% of VIII incarriers . Noneonatal GBS infection occurred under the empirically treatment . CONCLUSION: The measurement of serum type-specific antibody against GBS would be informative for the cost-benefit treatment of the vaginal GBS in pregnant women.

Obstet Gynecol, 2000 Oct, 96(4), 533 - 8
Prelabor rupture of the membranes at term: expectant management at home or in hospital? The TermPROM Study Group; Hannah ME et al.; OBJECTIVE: To determine whether adverse effects of expectant management for premature rupture of membranes (PROM) at term and patient satisfaction were greater if women were managed at home rather than in a hospital . METHODS: We undertook a secondary analysis of data from the International TermPROM Study for women managed expectantly at home or in a hospital . Using multiple logistic regression analyses, we determined the effect of home and hospital management and controlled for differences in baseline characteristics, in measures of maternal and neonatal infections and rates of cesarean . RESULTS: Six hundred fifty-three women (39.1%) were managed at home, and 1017 (60.9%) in a hospital . Management at home, compared with in a hospital, increased risk of nulliparas needing antibiotics before delivery (odds ratio {OR} 1.52 95% confidence interval {CI} 1.04, 2.24, P =.03), those not colonized with group B streptococcus having cesareans (OR 1.48 95% CI 1.03, 2 . 14, P =.04), and neonatal infections (OR 1.97 95% CI 1.00, 3.90, P = . 05) . More multiparas managed at home said they would participate in the study again (OR 1.80 95% CI 1.27, 2.54, P <.001) . CONCLUSION: Expectant management at home, rather than in a hospital, might increase the likelihood of some adverse outcomes.

J Bacteriol, 2000 Oct, 182(20), 5919 - 21
The Streptococcus pneumoniae beta-galactosidase is a surface protein; Zahner D et al.; The beta-galactosidase gene of Streptococcus pneumoniae, bgaA, encodes a putative 2,235-amino-acid protein with the two amino acid motifs characteristic of the glycosyl hydrolase family of proteins . In addition, an N-terminal signal sequence and a C-terminal LPXTG motif typical of surface-associated proteins of gram-positive bacteria are present . Trypsin treatment of cells resulted in solubilization of the enzyme, documenting that it is associated with the cell envelope . In order to obtain defined mutants suitable for lacZ reporter experiments, the bgaA gene was disrupted, resulting in a complete absence of endogenous beta-galactosidase activity . The results are consistent with beta-galactosidase being a surface protein that seems not to be involved in lactose metabolism but that may play a role during pathogenesis.

Oral Dis, 2000 Sep, 6(5), 289 - 96
Effects of antibodies to glucosyltransferase on soluble and insolubilized enzymes; Wunder D et al.; OBJECTIVE: Previous studies have shown that glucosyltransferase enzymes (Gtfs) of Streptococcus mutans adsorbed to saliva coated hydroxyapatite (sHA) have distinct properties from the same enzymes in solution . The purpose of the present study was to determine the effects on enzyme activity of polyclonal antibodies raised to Gtfs in a soluble form and bound to sHA . MATERIALS AND METHODS: Antiserum was raised in six New Zealand White rabbits using the purified glucosyltransferase enzymes (Gtfs) of S . mutans, GtfB, GtfC, or GtfD as soluble antigens or adsorbed to hydroxyapatite (HA, insolubilized) . The antisera were examined for their ability to react to these Gtfs and Gtf from Streptococcus sanguis (GtfSs) in Western blot formats as well as inhibit enzyme activity in solution and insolubilized . RESULTS: Antibodies raised against GtfB or GtfC detected all Gtf enzymes examined in Western blots; antibodies raised to GtfD reacted strongly to GtfD and GtfSs, poorly to GtfC, and was non-reactive with GtfB . Antibodies to GtfB or GtfC inhibited activity of GtfB and GtfC in solution by 90% or more . Enzyme activity adsorbed to sHA was inhibited from 70% to 80% by the same antisera . These same antibodies possessed no specific effect on the activities of either GtfD or GtfSs . Antibodies raised to the GtfD enzyme inhibited activity of GtfD (80% to 90% inhibition) and GtfSs activity (50% to 80%) in solution . In contrast the GtfD antibodies had no effect on the activity of either GtfB or GtfC enzymes in solution . Modest inhibitory effects were noted on GtfC and GtfSs enzymes bound to sHA, but no inhibition was observed for sHA-bound GtfB or GtfD . CONCLUSION: These data show that some antibodies effective against enzymes in solution may have significantly lesser inhibitory effects against the same enzymes insolubilized . Further, presentation of Gtf antigen immobilized to HA has only a minor influence on the production of antibodies inhibitory to Gtf activity.

Pediatr Infect Dis J, 2000 Sep, 19(9), 924 - 8
Diagnosis and management of pneumonia in children; McCracken GH Jr; BACKGROUND: This paper describes challenges in etiologic diagnosis and treatment of childhood community-acquired pneumonia and the means of addressing some of them . MICROBIOLOGICAL DIAGNOSIS: From about one-third to two-thirds of cases of pneumonia can be attributed to a specific etiology depending on which culture, antigen detection and specialized serologic techniques, some of which are unavailable to clinicians, are used . Results of studies in which microbiologic causes have been sought confirm the importance of Streptococcus pneumoniae as the primary bacterial cause of pneumonia in infants and children . Viral etiologies become less prevalent and mycoplasmal and chlamydial infections become more prevalent with increasing age . EMPIRIC TREATMENT: Because definitive information about causative pathogens is seldom available, treatment of pneumonia is most often empiric . Antibiotic therapy can be withheld in mildly ill, ambulatory patients in whom viral infection is likely . Most guidelines suggest initial treatment with orally administered amoxicillin or amoxicillin/clavulanate or with intravenous cefuroxime when patients require hospitalization . In May, 2000, the Centers for Disease Control-convened Drug-Resistant S . pneumoniae Therapeutic Working Group identified oral beta-lactams including cefuroxime axetil, amoxicillin and amoxicillin/clavulanate as appropriate options for first line therapy of community-acquired pneumonia in ambulatory adults and children . CONCLUSIONS: New diagnostic techniques such as pneumococcal serologies and polymerase chain reaction testing have improved the ability to determine the microbiologic etiology of childhood pneumonia . Because these tests are not generally available, empiric treatment is necessary . Efforts to identify new intervention strategies, diagnostic tools, therapies and vaccines will be helpful in managing this disease.

Pediatr Infect Dis J, 2000 Sep, 19(9), 917 - 23
Penicillin failure in streptococcal tonsillopharyngitis: causes and remedies; Pichichero ME et al.; Penicillin administered for 10 days has been the treatment of choice for group A beta-hemolytic streptococcal tonsillopharyngitis since the 1950s . The bacteriologic failure rate of 10 days of penicillin therapy ranged from approximately 2 to 10% until the early 1970s . Beginning in the late 1970s bacteriologic and clinical failure rates with penicillin therapy began to increase steadily over time and are now reported to be approximately 30% . The primary cause of penicillin treatment failure in streptococcal tonsillopharyngitis may be lack of compliance with the 10-day therapeutic regimen . Other causes of penicillin treatment failure include reexposure to Streptococcus-infected family members or peers; copathogenicity, in which bacteria susceptible to a class of drugs are protected by other, colocalized bacterial strains that lack the same susceptibility; antibiotic-associated eradication of normal protective pharyngeal flora; and penicillin tolerance, whereby streptococcal bacteria repeatedly or continuously exposed to sublethal concentrations of antibiotic become increasingly resistant to eradication . Although 10 days of penicillin therapy is effective in the management of tonsillopharyngitis for many patients, multiple factors may, singly or together, cause treatment failure . A number of antibiotics, particularly the cephalosporins, have been demonstrated to be superior to penicillin at eradicating group A beta-hemolytic Streptococcus, and several are effective when administered for 4 to 5 days . CONCLUSIONS: Ten days of penicillin therapy may not be the best therapeutic choice for all pediatric patients . Other antibiotics, shortened courses of the cephalosporins in particular, may be preferable in some cases.

Arch Intern Med, 2000 Sep 25, 160(17), 2633 - 8
Evaluation of effectiveness of the 23-valent pneumococcal capsular polysaccharide vaccine for HIV-infected patients; Breiman RF et al.; BACKGROUND: We conducted a retrospective case-control study to evaluate effectiveness of pneumococcal vaccine against invasive disease among adults with human immunodeficiency virus (HIV) infection in San Francisco, Calif, and Atlanta, Ga . METHODS: Case patients were 18- to 55-year-old subjects with HIV infection who were admitted to selected hospitals in Atlanta or San Francisco from February 1992 to April 1995 from whom Streptococcus pneumoniae was isolated from a normally sterile site . Controls were HIV-infected patients of similar age matched to cases by hospital of admission and CD4 lymphocyte count (<0.20, 0.20-0.499, >/=0.50 x 10(9)/L {<200, 200-499, >/=500 cells/mm(3)}) or clinical stage of acquired immunodeficiency syndrome . Case and control subjects were restricted to persons known to have HIV infection before hospital admission . Analysis used matched univariate and conditional logistic regression . RESULTS: One hundred seventy-six case patients and 327 controls were enrolled . By univariate analysis, persons with pneumococcal disease were more likely to be black, be current smokers, and have close contact with children . Adjusted for these factors and CD4 cell count, pneumococcal vaccine effectiveness was 49% (95% confidence interval {CI}, 12%-70%) . Adjusting for all variables and key interaction terms, vaccine effectiveness among whites was 76% (95% CI, 35%-91%), whereas effectiveness among blacks was 24% (95% CI, -50% to 61%) . Among controls, vaccination was significantly less common among blacks (29% vs 45%; P<.005) . CONCLUSIONS: Pneumococcal vaccine demonstrated protection against invasive pneumococcal infections among white but not black HIV-infected adults . Failure to demonstrate effectiveness among blacks may be due to limited power because of low use of the vaccine in this population, immunization at more advanced stages of immunosuppression, or unmeasured factors . These data support current recommendations for use of pneumococcal vaccine in HIV-infected persons and highlight a clear need for strategies to improve vaccine-induced protection.

Arch Dis Child, 2000 Oct, 83(4), 320 - 4
Rationalised prescribing for community acquired pneumonia: a closed loop audit; Clements H et al.; AIMS: To audit the management of community acquired pneumonia before and after the introduction of a protocol . To determine the aetiology of pneumonia using routine investigations and polymerase chain reaction (PCR) . METHODS: Retrospective and prospective audit following the introduction of a management protocol . Prospective cases were investigated routinely and with PCR on blood and nasopharyngeal aspirate . RESULTS: There was a significant increase in rational prescribing following introduction of the protocol with 75% of children receiving intravenous penicillin or erythromycin compared with 26% beforehand . Of 89 children in the prospective group, 51 microbiological diagnoses were achieved in 48 children . Seven children had Streptococcus pneumoniae infection, 14 had Mycoplasma infection, six had pertussis, and one had Chlamydia pneumoniae infection . Twenty three children had a viral cause of which respiratory syncytial virus was commonest . CONCLUSIONS: Introduction of the protocol led to improved prescribing . PCR increased the diagnostic yield and the results support the management protocol.

Emerg Infect Dis, 2000 Sep-Oct, 6(5), 552 - 6
Antimicrobial-drug use and changes in resistance in Streptococcus pneumoniae; Diekema DJ et al.; Resistance of Streptococcus pneumoniae to antimicrobial drugs is increasing . To investigate the relationship between antimicrobial use and susceptibility of S . pneumoniae isolates at 24 U.S . medical centers, we obtained data on outpatient antimicrobial-drug use for the regions surrounding 23 of these centers . We found an association between decreased penicillin susceptibility and use of beta-lactam antimicrobial drugs.

Mol Microbiol, 2000 Sep, 37(6), 1444 - 55
Identification of Streptococcus agalactiae virulence genes in the neonatal rat sepsis model using signature-tagged mutagenesis; Jones AL et al.; Group B streptococcal (GBS) infections are the most common cause of bacterial sepsis in the immediate newborn period . Apart from the capsule, the factors required for survival of GBS in the host are not well defined . In this study, signature-tagged transposon mutagenesis (STM) was used to identify genes required for growth and survival of GBS in a neonatal rat sepsis infection model . Approximately 1600 transposon mutants were screened in pools of 80 mutants, and approximately 120 mutants defective for survival in the animal host were identified . We successfully cloned and sequenced DNA flanking the transposon insertions from 92 of the mutants . Fifty per cent of the mutants had transposon insertions in genes with homologues in the public databases, whereas the remaining 50% had transposon insertions in genes with unknown function . A significant proportion of the avirulent mutants had transposon insertions in genes encoding transport-associated or regulatory proteins or in genes involved in cell surface metabolism, emphasizing the significance of these functions for in vivo survival of GBS . Overall, STM analysis revealed GBS genomic loci that encode a wide variety of functional gene classes, underscoring the diversity of bacterial processes required for the infection process . Currently, the function of the genes identified during the screening can only be inferred by homology to previously described genes . However, a number of the genes identified in this study have been shown to correlate with virulence in other pathogens . A virulence of a subset of mutants identified during the screening was confirmed by performing competitive index assays and lethal dose assays . This represents the first report of a genome-wide scan for virulence factors in GBS . The identified genes will further our understanding of the pathogenesis of GBS infections and may represent targets for intervention or lead to the development of novel therapies.

J Trop Pediatr, 2000 Aug, 46(4), 237 - 9
Neonatal meningitis: mortality, cerebrospinal fluid, and microbiological findings; Nel E; This study describes the bacteriology, cerebrospinal fluid (CSF) findings, and mortality of neonatal meningitis over an 11-year period . The minimum incidence of neonatal meningitis at Tygerberg Hospital is 0.72/1000 live births/year . Eighty-eight patients were included in the study . Median birthweight and age at diagnosis were 2320 g and 12 days, respectively . CSF culture was positive in 77 (88 per cent), blood culture was positive in 51 (57 per cent), and Gram stain was positive in 58 (66 per cent) . The most frequently cultured organisms were Group B Streptococcus, Klebsiella pneumoniae, and E . coli . Thirty (34 per cent) patients died, the majority within 72 h after admission . The death rate was significantly increased in babies with a birthweight of less than 1500 g (59 per cent) . Increased total CSF protein was associated with an increased risk of death . Normal CSF cell count, total CSF protein and CSF glucose were found in six infants.

Int J Pediatr Otorhinolaryngol, 2000 Sep 15, 55(1), 1 - 9
Experimental study of the virulence of Streptococcus pneumoniae with reduced susceptibility to penicillin; Magnusdottir AB et al.; Streptococcus pneumoniae is a major cause of morbidity and mortality in all age groups . In a few years, penicillin non-susceptible pneumococci (PNSP) have emerged worldwide as a new threat . In order to better understand the mechanisms behind the rapid expansion of these strains, the virulence of 10 clinical and two transformed PNSP strains were compared with the virulence of three fully susceptible strains in a mouse model of bacteremia and a rat model of acute otitis media . Serotype, antibiotic susceptibility, and to some extent also genetic profile and growth rate of the strains were investigated before inoculation . The animals were monitored for up to 7 days after challenge by clinical examinations/otomicroscopy and cultures from middle ears and blood . The results of the study demonstrated that the PNSP strains had a significantly reduced ability to persist at the infectious site, and to some extent also to induce infections, compared with fully susceptible strains . The reduction was most evident for strains isolated from sources other than blood . It is therefore possible that other factors than virulence factors are of importance for the ability of PNSP strains to expand.

Fish Shellfish Immunol, 2000 Jul, 10(5), 419 - 34
In vivo activation of tilapia nonspecific cytotoxic cells by Streptococcus iniae and amplification with apoptosis regulatory factor(s); Evans DL et al.; An important component of immediate innate responses of tilapia to stress is the release within minutes of soluble cytokine-like substances into the peripheral circulation . These cytokine-like stress factors bind nonspecific cytotoxic cells (NCC) and produce 3-4-fold increased cytotoxicity . In the present study, the in vivo responses of tilapia NCC following injection with different isolates of intact killed Streptococcus iniae was investigated . Activated cytotoxicity of NCC in the peripheral blood (PB) was produced by increased specific activity of resident cells rather than increased numbers . Tilapia injected intravenously (i.v.) with killed S . iniae produced different cytotoxicity responses compared to fish injected intraperitoneally (i.p.) . In the spleen (S) and anterior kidney (AK), there was no correlation between S . iniae isolate and cytotoxicity response at 4, 8 or 24 h following i.p . injection . The NCC response following i.v . injection of killed bacteria was different . Within minutes following i.v . injection, NCC cytotoxicity from the PB increased 100% compared to naive controls . The existence of subsets of differentiated NCC in the PB was suggested because i.v . injection had no amplification effects on NCC from the AK or S . Likewise, NCC from the PB only appeared to exhibit a degree of antigen specificity . S . iniae strain #173 produced activation of cytotoxicity compared to isolates #164 and ATCC . Evidence for soluble factor (cytokine?) involvement in increased cytotoxicity was obtained by passive activation of NCC with serum from #173 (i.v.) injected fish . Incubation of this serum with control (naive) NCC produced large increases in the cytotoxicity of labelled HL-60 target cells . Similarly obtained serum from fish injected with ATCC and #164 isolates had no amplification activity . Studies were also performed to study the mechanism(s) of passive activation . Flow cytometric analysis revealed that NCC from the S, AK and PB constitutively expressed cytosolic (not membrane) FasL . Stress serum treated NCC obtained from the peripheral blood produced an increase in the expression of FasL, CAS and FADD by Western blot examination . These data indicated that cytokine like factors in the serum of stressed tilapia activate increased NCC cytotoxicity (possibly) by stimulating the expression of proteins involved in activation of programmed cell death.

Can Vet J, 2000 Sep, 41(9), 704 - 6
Septic orchitis in an alpaca; Aubry P et al.; An adult, intact male alpaca was presented with an acute onset of unilateral scrotal swelling . Following complete physical and ultrasonographic examination, the most likely differential diagnoses were orchitis, hematoma, and testicular torsion . The animal was castrated and histopathologic evaluation revealed unilateral orchitis . Streptococcus equi subsp . zooepidemicus was cultured.

J Pak Med Assoc, 2000 Aug, 50(8), 256 - 9
Bacteriology of surgical site infections and antibiotic susceptibility pattern of the isolates at a tertiary care hospital in Karachi; Mahmood A; OBJECTIVE: To study post surgical infections and sensitivity of the Isolates so that recommendations can be made for their prevention and empirical antibiotic treatment . SETTING: Swabs/pus specimens from the patients developing surgical site infections at PNS Shifa, Karachi were processed in the Department of Pathology during January, 1998 to September, 1999 . METHODS: One hundred and twenty-nine swabs/pus specimens from various types of surgical sites suspected to be infected on clinical grounds were processed, by standard methods and antibiotic susceptibility testing of all the isolates was done by using Modified Kirby Baur disc diffusion technique . RESULTS: Of the one hundred and fifty-three organisms isolated, the most common was Staphylococcus aureus (50.32%), followed by Pseudomonas aeruginosa (16.3%), Escherichia coli (14.37%), Klebsiella pneumoniae (11.76%), miscellaneous gram negative rods (5.88%) and Streptococcus pyogenes (1.30%) . About 50% of the Staphylococcus aureus isolates were found to be methicillin resistant . In case of Pseudomonas aeruginosa and Escherichia coli more than 60% of the isolates were found resistant to Gentamicin . The resistance to third generation cephalosporins and the quinolone ciprofloxacin was also quite high . Other isolates also showed a very high level of antibiotic resistance . CONCLUSION: In addition to the economic burden for antibiotic treatment, such infections for multi-resistant organisms are a serious threat to our surgical patients . To prevent these happenings, there is an urgent need to adopt basic principles of asepsis and sterilisation and to make judicious use of prophylactic and therapeutic antibiotics.

Infect Immun, 2000 Oct, 68(10), 6082 - 6
Peritoneal culture alters Streptococcus pneumoniae protein profiles and virulence properties; Orihuela CJ et al.; We have examined the properties of Streptococcus pneumoniae cultured in the murine peritoneal cavity and compared its virulence-associated characteristics to those of cultures grown in vitro . Analysis of mRNA levels for specific virulence factors demonstrated a 2.8-fold increase in ply expression and a 2.2-fold increase in capA3 expression during murine peritoneal culture (MPC) . Two-dimensional gels and immunoblots using convalescent-phase patient sera and murine sera revealed distinct differences in protein production in vivo (MPC) . MPC-grown pneumococci adhered to A549 epithelial cell lines at levels 10-fold greater than those cultured in vitro.

Infect Immun, 2000 Oct, 68(10), 6048 - 51
Identification of lipoprotein homologues of pneumococcal PsaA in the equine pathogens Streptococcus equi and Streptococcus zooepidemicus; Harrington DJ et al.; Streptococcus equi and Streptococcus zooepidemicus are major etiological agents of upper and lower airway disease in horses . Despite the considerable animal suffering and economic burden associated with these diseases, the factors that contribute to the virulence of these equine pathogens have not been extensively investigated . Here we demonstrate the presence of a homologue of the Streptococcus pneumoniae PsaA protein in both of these equine pathogens . Inhibition of signal peptide processing by the antibiotic globomycin confirmed the lipoprotein nature of the mature proteins, and surface exposure was confirmed by their release from intact cells by mild trypsinolysis.

Infect Immun, 2000 Oct, 68(10), 5889 - 900
Diversity of PspA: mosaic genes and evidence for past recombination in Streptococcus pneumoniae; Hollingshead SK et al.; Pneumococcal surface protein A (PspA) is a serologically variable protein of Streptococcus pneumoniae . Twenty-four diverse alleles of the pspA gene were sequenced to investigate the genetic basis for serologic diversity and to evaluate the potential of diversity to have an impact on PspA's use in human vaccination . The 24 pspA gene sequences from unrelated strains revealed two major allelic types, termed "families," subdivided into clades . A highly mosaic gene structure was observed in which individual mosaic sequence blocks in PspAs diverged from each other by over 20% in many cases . This level of divergence exceeds that observed for blocks in the penicillin-binding proteins of S . pneumoniae or in many cross-species comparisons of gene loci . Conversely, because the mosaic pattern is so complex, each pair of pspA genes also has numerous shared blocks, but the position of conserved blocks differs from gene pair to gene pair . A central region of pspA, important for eliciting protective antibodies, was found in six clades, which each diverge from the other clades by >20% . Sequence relationships among the 24 alleles analyzed over three windows were discordant, indicating that intragenic recombination has occurred within this locus . The extensive recombination which generated the mosaic pattern seen in the pspA locus suggests that natural selection has operated in the history of this gene locus and underscores the likelihood that PspA may be important in the interaction between the pneumococcus and its human host.

Infect Immun, 2000 Oct, 68(10), 5778 - 84
Peptide mimic of phosphorylcholine, a dominant epitope found on Streptococcus pneumoniae; Harris SL et al.; Even in the age of antibiotics, Streptococcus pneumoniae causes significant morbidity, especially in the young, the elderly, and the immunocompromised . While a carbohydrate-based vaccine exists, it is poorly immunogenic in the at-risk populations . In mice, antibodies directed against phosphorylcholine (PC), an epitope present on the cell wall C polysaccharide of all pneumococcal serotypes, protect against infection . However, PC itself is a poor vaccine candidate . We report here peptide mimics of PC based on the anti-idiotypic interaction of T15 anti-PC antibodies . T15 antibodies, the dominant and protective idiotype induced in mice by PC immunization, self-associate via a 24-amino-acid region in the PC binding site (ASRNKANDYTTEYSASVKGRFIVS; peptide 1) . Peptide 1 has been shown to bind in the PC binding site . We demonstrated that amino acid sequences derived from peptide 1 starting at amino acid 9, 11, or 13 inhibit PC binding . Therefore, we immunized mice with bovine serum albumin (BSA) conjugates of peptide 1 or either of two selected 12-mers . The 12-mer peptides were not immunogenic . Mice immunized with peptide 1-BSA developed an anti-PC response consisting mainly immunoglobulin G1 and expressed the T15 heavy chain . Nonetheless, neither BALB/c nor CBA/N mice were protected from lethal pneumococcal infections by immunization with peptide 1-BSA . Preliminary data suggest that peptide 1-BSA is not able to elicit the canonical T15 light chain, explaining the absence of protection . This idiotype-derived mimotope of PC is a useful tool for understanding immunologic cross-reactivity and learning to design T-cell-dependent vaccines for S . pneumoniae.

Infect Immun, 2000 Oct, 68(10), 5690 - 5
Role of novel choline binding proteins in virulence of Streptococcus pneumoniae; Gosink KK et al.; The choline binding proteins (CBPs) are a family of surface proteins noncovalently bound to the phosphorylcholine moiety of the cell wall of Streptococcus pneumoniae by a conserved choline binding domain . Six new members of this family were identified, and these six plus two recently described cell wall hydrolases, LytB and LytC, were characterized for their roles in virulence . CBP-deficient mutants were constructed and tested for adherence to eukaryotic cells, colonization of the rat nasopharynx, and ability to cause sepsis . Five CBP mutants, CbpD, CbpE, CbpG, LytB, and LytC, showed significantly reduced colonization of the nasopharynx . For CbpE and -G this was attributable to a decreased ability to adhere to human cells . CbpG, a putative serine protease, also played a role in sepsis, the first observation of a pneumococcal virulence determinant strongly operative both on the mucosal surface and in the bloodstream.

Infect Immun, 2000 Oct, 68(10), 5645 - 51
B-Cell deficiency predisposes mice to disseminating anaerobic infections: protection by passive antibody transfer; Hou L et al.; We have previously demonstrated that a high proportion of RAG-2 SCID knockout mice, which lack T and B cells, develop orofacial abscesses and disseminated infections following pulpal infection, whereas immunocompetent control mice do not . In the present study, we sought to identify the components of the adaptive immune response which contribute to protection against disseminating anaerobic infections and sepsis . For this purpose, various genetically engineered immunodeficient mice were employed, including RAG-2 SCID, Igh-6 (B-cell deficient), Tcrb Tcrd (T-cell deficient) and Hc(0) (C5 deficient) . For abscess induction, the mandibular first molars were subjected to pulp exposure on day 0 . Teeth were infected with a mixture of four anaerobic pathogens, including Prevotella intermedia, Streptococcus intermedius, Fusobacterium nucleatum, and Peptostreptococcus micros, and teeth were sealed to prevent communication with the oral cavity . The findings demonstrate that both RAG-2 SCID and B-cell-deficient mice, but not T-cell- or C5-deficient mice, have increased susceptibility to the development of disseminating anaerobic infections . Abscess-susceptible RAG-2 SCID and B-cell-deficient mice also showed a significant loss of body weight, splenomegaly, and absent antibacterial antibody production . Furthermore, dissemination was significantly reduced, from 74 to 25%, in susceptible RAG-2 mice by passively transferred antibody, predominantly immunoglobulin G2b (IgG2b) and IgM, against the infecting bacterial innoculum . Fractionated IgG-enriched preparations were more efficient in transferring protection than IgM preparations . We conclude that an antibody-mediated mechanism(s), most likely bacterial opsonization, is of importance in localizing anaerobic root canal infections and in preventing their systemic spread.

Infect Immun, 2000 Oct, 68(10), 5539 - 45
Generation of female genital tract antibody responses by local or central (common) mucosal immunization; Wu HY et al.; Genital antibody responses were compared in female mice immunized intravaginally (i.vag.) or intranasally (i.n.) with a bacterial protein antigen (AgI/II of Streptococcus mutans) coupled to the B subunit of cholera toxin . Serum and salivary antibodies were also evaluated as measures of disseminated mucosal and systemic responses . Although i.vag . immunization induced local vaginal immunoglobulin A (IgA) and IgG antibody responses, these were not disseminated to a remote secretion, the saliva, and only modest levels of serum antibodies were generated . In contrast, i.n . immunization was substantially more effective at inducing IgA and IgG antibody responses in the genital tract and in the circulation, as well as at inducing IgA antibodies in the saliva . Moreover, mucosal and systemic antibodies induced by i.n . immunization persisted for at least 12 months . Analysis of the molecular form of genital IgA indicated that the majority of both total IgA and specific IgA antibody was polymeric, and likely derived from the common mucosal immune system.

Antimicrob Agents Chemother, 2000 Oct, 44(10), 2802 - 10
Deregulation of the arginine deiminase (arc) operon in penicillin-tolerant mutants of Streptococcus gordonii; Caldelari I et al.; Penicillin tolerance is an incompletely understood phenomenon that allows bacteria to resist drug-induced killing . Tolerance was studied with independent Streptococcus gordonii mutants generated by cyclic exposure to 500 times the MIC of penicillin . Parent cultures lost 4 to 5 log(10) CFU/ml of viable counts/24 h . In contrast, each of four independent mutant cultures lost < or =2 log(10) CFU/ml/24 h . The mutants had unchanged penicillin-binding proteins but contained increased amounts of two proteins with respective masses of ca . 50 and 45 kDa . One mutant (Tol1) was further characterized . The two proteins showing increased levels were homologous to the arginine deiminase and ornithine carbamoyl transferase of other gram-positive bacteria and were encoded by an operon that was >80% similar to the arginine-deiminase (arc) operon of these organisms . Partial nucleotide sequencing and insertion inactivation of the S . gordonii arc locus indicated that tolerance was not a direct consequence of arc alteration . On the other hand, genetic transformation of tolerance by Tol1 DNA always conferred arc deregulation . In nontolerant recipients, arc was repressed during exponential growth and up-regulated during postexponential growth . In tolerant transformants, arc was constitutively expressed . Tol1 DNA transformed tolerance at the same rate as transformation of a point mutation (10(-2) to 10(-3)) . The tolerance mutation mapped on a specific chromosomal fragment but was physically distant from arc . Importantly, arc deregulation was observed in most (6 of 10) of additional independent penicillin-tolerant mutants . Thus, although not exclusive, the association between arc deregulation and tolerance was not fortuitous . Since penicillin selection mimicked the antibiotic pressure operating in the clinical environment, arc deregulation might be an important correlate of naturally occurring tolerance and help in understanding the mechanism(s) underlying this clinically problematic phenotype.

Antimicrob Agents Chemother, 2000 Oct, 44(10), 2740 - 6
In vitro selection of resistance to clinafloxacin, ciprofloxacin, and trovafloxacin in Streptococcus pneumoniae; Nagai K et al.; Ability of daily sequential subcultures in subinhibitory concentrations of clinafloxacin, ciprofloxacin, and trovafloxacin to select resistant mutants was studied in 10 pneumococci (ciprofloxacin MICs, 1 to 4 microg/ml, and clinafloxacin and trovafloxacin MICs, 0.06 to 0.125 microg/ml {n = 9}; ciprofloxacin, clinafloxacin, and trovafloxacin MICs, 32, 0.5, and 2 microg/ml, respectively {n = 1}) . Subculturing was done 50 times, or until MICs increased fourfold or more . Mutants for which MICs were fourfold (or more) higher than those for parent strains were selected in five strains by clinafloxacin, in six strains by trovafloxacin, and nine strains by ciprofloxacin . Sequence analysis of type II topoisomerase showed that most mutants had mutations in ParC at Ser79 or Asp83 and in GyrA at Ser81, while a few mutants had mutations in ParE or GyrB . In the presence of reserpine, the MICs of ciprofloxacin and clinafloxacin for most mutants were lower (four to eight times lower), but for none of the mutants were trovafloxacin MICs lower, suggesting an efflux mechanism affecting the first two agents but not trovafloxacin . Single-step mutation rates were also determined for eight strains for which the MICs were as follows: 0.06 microg/ml (clinafloxacin), 0.06 to 0.125 microg/ml (trovafloxacin), and 1 microg/ml (ciprofloxacin) . Single-step mutation rates with drugs at the MIC were 2.0x10(-9) to <1.1x10(-11), 5.0x10(-4) to 3.6x10(-9), and 4.8x10(-4) to 6.7x10(-9), respectively . For two strains with clinafloxacin MICs of 0.125 to 0.5 microg/ml trovafloxacin MICs of 0 . 125 to 2 microg/ml, ciprofloxacin MICs of 4 to 32 microg/ml mutation rates with drugs at the MIC were 1.1x10(-8)-9.6x10(-8), 3.3x10(-6)-6 . 7x10(-8), and 2.3x10(-5)-2.4x10(-7), respectively . Clinafloxacin was bactericidal at four times the MIC after 24 h against three parent and nine mutant strains by time-kill study . This study showed that single and multistep clinafloxacin exposure selected for resistant mutants less frequently than similar exposures to other drugs studied.

Antimicrob Agents Chemother, 2000 Oct, 44(10), 2615 - 8
Antibody-targeted lethal photosensitization of Porphyromonas gingivalis; Bhatti M et al.; We have previously demonstrated that Porphyromonas gingivalis is susceptible to killing by toluidine blue O (TBO) when irradiated with light from a helium-neon (HeNe) laser . The aim of this study was to determine whether a TBO-antibody conjugate (Ab-TBO) could be used to specifically target P . gingivalis to lethal photosensitization in the presence of Streptococcus sanguis or human gingival fibroblasts (HGFs) . When a mixture of P . gingivalis and S . sanguis was exposed to 4 microg of TBO/ml and irradiated with HeNe laser light, there were 1.5- and 4.0-log(10)-unit reductions in the viable counts, respectively . In contrast, when TBO was conjugated with a murine monoclonal antibody against P . gingivalis lipopolysaccharide, the reductions in viable counts of P . gingivalis and S . sanguis amounted to 5.0 and 0.1 log(10) units, respectively . Lethal photosensitization of P . gingivalis in the presence of HGFs using unconjugated TBO resulted in a 0.7-log(10)-unit reduction in P . gingivalis viable counts and a 99% reduction in the incorporation of tritiated thymidine ({(3)H}Tdr) by the HGFs . In contrast, when the Ab-TBO conjugate was used, there was a 100% reduction in P . gingivalis viable counts but no significant reduction in the incorporation of {(3)H}Tdr by HGFs . These results demonstrate that specific targeting of P . gingivalis can be achieved using TBO conjugated to a monoclonal antibody raised against a cell surface component of this organism.

Microb Drug Resist, 2000 Summer, 6(2), 163 - 70
Antibiotic susceptibility patterns and serotypes of antibiotic resistant and/or invasive Streptococcus pneumoniae strains circulating in Italy; Marchese A et al.; Antibiotic susceptibility patterns and serotypes of 397 Streptococcus pneumoniae recovered from 1994 to 1998 in Italy have been determined . This collection included 229 penicillin- and/or erythromycin-resistant strains and 168 isolates responsible for invasive infections . Among penicillin-resistant pneumococci, the most prevalent serotype was 23F, followed by 19F and 9V, while among erythromycin-resistant but penicillin-susceptible strains serotype 6B was predominant followed by 19A, 14, 19F, 15A, 15B, and 23F . The most common invasive serotypes were 6B, 19F, 23F, 3, 4, 14, 20, 15B, and 9N . The currently available 23-valent pneumococcal vaccine could cover 91% of noninvasive penicillin- and/or erythromycin-resistant strains, 84% of pneumococci isolated from sterile sites, and 83% of invasive antibiotic-resistant S . pneumoniae . Penicillin-resistant pneumococci also showed reduced susceptibility to other antimicrobial compounds . Against invasive pneumococci, amoxicillin, cefotaxime, ceftriaxone, imipenem, vancomycin, and rifampin were 100% effective . Penicillin, chloramphenicol, erythromycin, tetracycline, and co-trimoxazole resistance was 1.8%, 9.5%, 15.5%, 18.5%, and 21.4%, respectively.

Microb Drug Resist, 2000 Summer, 6(2), 127 - 31
Analysis of penicillin-binding protein lb and 2a genes from Streptococcus pneumoniae; Du Plessis M et al.; Fifty clinical isolates (penicillin MICs, 0.03-8 microg/mL) of Streptococcus pneumoniae were randomly selected from hospitals throughout South Africa, together with seven strains isolated in Hungary (penicillin MICs, 16-32 microg/mL) . Penicillin-binding protein (pbp) 1b and 2a genes were amplified by PCR, and the purified DNA was digested with HinfI, StyI, and MseI + DdeI restriction enzymes . The fragments were radioactively end-labeled and separated on polyacrylamide gels, and the DNA fingerprints were visualized following autoradiography . A collection of isolates was further selected for sequence analysis of pbp1b and 2a . DNA fingerprint analysis revealed a uniform profile amongst all isolates for both genes . All isolates revealed a maximum of only seven nucleotide substitutions in their pbp1b genes, resulting in a maximum of three amino acid substitutions in PBP 1B . In the case of the pbp2a gene, up to 13 nucleotide substitutions were observed randomly distributed amongst penicillin-susceptible and resistant isolates, revealing a maximum of five amino acid substitutions in PBP 2A . No amino acid substitutions were found to be common amongst all penicillin-resistant isolates . Transformation experiments with pbp1b and 2a genes isolated from two resistant strains (MICs, 4 and 16 microg/mL) failed to transform pneumococcal strains to increased levels of penicillin resistance . These results show that the pbp1b and 2a genes examined here do not display the typical mosaic gene patterns observed in the pbp2x, 2b, and 1a genes of penicillin-resistant pneumococci . In addition, the transformation studies suggest that PBPs 1B and 2A may not play a role in the development of penicillin resistance in some pneumococci.

Microb Drug Resist, 2000 Summer, 6(2), 105 - 10
Non-Penicillin-Binding protein mediated high-level penicillin and cephalosporin resistance in a Hungarian clone of Streptococcus pneumoniae; Smith AM et al.; A clone of Hungarian pneumococcal strains has recently been isolated with notably high levels of beta-lactam resistance (penicillin MIC, 16 microg/mL; cefotaxime MIC, 4 microg/mL) . The role that each penicillin-binding protein (PBP) plays in the development of resistance in these strains was investigated via transformation of susceptible strain R6 with pbp DNA from resistant strain 3191 . Transformation of strain R6 with pbp2X DNA resulted in transformants with penicillin and cefotaxime MICs of 0.06 and 0.25 microg/mL, respectively . Further introduction of pbp2B and 1A DNA increased penicillin MICs to 0.25 and 4 microg/mL, respectively . Transformation of strain R6 with a combination of pbp2X and pbp1A DNA produced R63191/2X/1A strains with an unexpected low cefotaxime MIC of 0.5 microg/mL . This low-level of cefotaxime resistance was surprisingly increased from 0.5 to 2 microg/mL in R63191/2X/2B/1A strains . This suggests the involvement of altered PBP 2B in cefotaxime resistance . Therefore, within this particular setting of resistance, the environmental presence of selectors for altered PBP 2B (penicillin or piperacillin) are required for the development of high-level cefotaxime resistance . The MICs of R63191/X/2B/1A strains never reached the MICs of the donor strain . Full MICs of the donor were eventually reached by transforming R63191/2X/2B with chromosomal3191 DNA . Resultant transformants revealed the introduction of altered PBP 1A, while unaltered PBPs 1B, 2A, and 3 proved that these PBPs were not involved in resistance . A non-PBP resistance determinant has therefore made up the difference in resistance between R63191/2X/2B/1A and donor strain 3191 . Beta-lactamase activity and efflux systems have so far been eliminated as causes of resistance . This resistance determinant represents a novel mechanism for beta-lactam resistance in clinical isolates of pneumococci, operates at the highest level of resistance, and remains to be identified.

Clin Infect Dis, 2000 Aug, 31(2), 613 - 5
Bacteremic pneumonia due to multidrug-resistant pneumococci in 3 patients treated unsuccessfully with azithromycin and successfully with levofloxacin; Fogarty C et al.; Three patients with bacteremic pneumonia caused by multidrug-resistant Streptococcus pneumoniae were treated unsuccessfully with azithromycin . One S . pneumoniae isolate carried a mef determinant for an efflux pump; a second isolate had an erm determinant . All 3 patients were successfully treated with levofloxacin, an antipneumococcal fluoroquinolone.

Clin Infect Dis, 2000 Aug, 31(2), 482 - 7 Epub 2000 Aug 30.
Proportion of invasive pneumococcal infections in German children preventable by pneumococcal conjugate vaccines; von Kries R et al.; The incidence and serotype distribution of Streptococcus pneumoniae as a cause of invasive diseases are unknown with regard to most European countries . From January 1997 through December 1998, population-based nationwide prospective surveillance was undertaken for invasive pneumococcal disease (IPD) in children in Germany, based on monthly independent reports from all pediatric hospitals and from clinical microbiology laboratories . On the basis of 896 reported IPD cases (including 404 with meningitis), the incidences per 10(5) children in different age groups were as follows: children aged <1 year, 18.9 (9.7 for meningitis); children aged <2 years, 16 . 0 (7.2 for meningitis); for children aged <5 years, 8.9 (3.9 for meningitis); and for children aged <16 years, 3.2 (1.4 for meningitis) . The proportions of cases involving strains (304 serotyped) included in conjugate vaccines were as follows: for the 7-valent vaccine, 52%; for the 9-valent, 62%; and for the 11-valent, 71% . None of the isolates were resistant to penicillin or cefotaxime . Although the rate for meningitis is similar, other manifestations of IPD are less commonly diagnosed in Germany than in other countries . The serotype distribution only partially matched that used in the recent development of pneumococcal conjugate vaccines.

Clin Infect Dis, 2000 Aug, 31(2), 464 - 71 Epub 2000 Sep 14.
Ampicillin/sulbactam and cefoxitin in the treatment of cutaneous and other soft-tissue abscesses in patients with or without histories of injection drug abuse; Talan DA et al.; A randomized, double-blind trial compared the clinical and bacteriologic efficacy of ampicillin/sulbactam (2 g/1 g) and cefoxitin (2 g) administered intravenously every 6 h to patients with (n=49) or without (n=47) histories of injection drug abuse who presented with cutaneous or other soft-tissue infections . Cure or improvement occurred in 89.8% of ampicillin/sulbactam-treated patients, compared with 93.6% of cefoxitin-treated patients . The median time to resolution of all symptoms was 10.5 days with ampicillin/sulbactam treatment and 15.5 days with cefoxitin treatment . Mixed aerobic-anaerobic infection was encountered frequently in both treatment groups . A significantly higher percentage of Streptococcus species was found in the major abscesses of the patients with histories of injection drug abuse, compared with those without such histories (37% vs . 19%, respectively; P=.0009) . Overall, ampicillin/sulbactam eradicated pathogens from the major abscesses in 100% of patients, whereas the eradication rate with cefoxitin was 97.9% . The 2 drugs were well tolerated . Ampicillin/sulbactam and cefoxitin were equally effective for the empirical treatment of cutaneous or other soft-tissue infections in injection drug abusers and patients who did not inject drugs.

JSLS, 2000 Jul-Sep, 4(3), 263 - 5
Unretrieved gallstones presenting as a Streptococcus bovis liver abscess; Steerman PH et al.; We describe a case of a delayed liver abscess presenting two years after a laparoscopic cholecystectomy . At exploration, the patient was found to have an unretrieved gallstone as the nidus for the Streptococcus bovis abscess.

Clin Chem Lab Med, 2000 Jun, 38(6), 545 - 51
A model for setting analytical quality specifications and design of control for measurements on the ordinal scale; Petersen PH et al.; A model for characterization of measurements on the ordinal scale is presented . It is based on transformation of the calculated fractions (fractiles) of positives from measurements on samples with known concentrations to a probit-natural log (probit-ln) scale . Such measurements could be made by other methods on ratio or difference scales but, for convenience (for example for speed or low cost), are measured on the ordinal scale by "simple" methods . The model is examined, and verified, using three examples from published data (haemoglobin, glucose, and leukocytes) and an external quality assessment survey on measurements of streptococcus . We show that it is possible to obtain reliable analytical quality specifications and to establish design of control systems for measurements on the ordinal scale . It is concluded that the presented probit-ln model for the ordinal scale is a tool which can improve and facilitate (i) characterizing methods with measurements on the ordinal scale, (ii) defining analytical quality specifications, (iii) designing external assessment as well as internal control schemes, (iv) validation of methods with measurements on the ordinal scale according to the analytical quality specifications, and further, (v) reduction of the number of samples required for method validation and the number of replicate measurements needed.

Aust N Z J Med, 2000 Aug, 30(4), 462 - 5
Group B streptococcal meningitis in adults: recent increase in Southeast Asia; Wilder-Smith E et al.; BACKGROUND: Meningitis caused by Streptococcus agalactiae (Group B Streptococcus) is rare in adults and usually affects patients with predisposing conditions . AIMS: To describe an increase in adult group B streptococcal meningitis occurring in parallel in Hong Kong and Singapore . METHODS: All cases of bacterial meningitis admitted to the Prince of Wales Hospital, Hong Kong and Singapore General Hospital in 1998, aged 15 years or above, were reviewed . Medical records for the previous ten years were searched for previous cases of adult group B streptococcal meningitis . RESULTS: In 1998, 29 adult patients with bacterial meningitis were admitted to the two hospitals . S . agalactiae was isolated in 11 cases, Streptococcus pneumoniae in three cases, Klebsiella pneumoniae in two cases, and Pseudomonas pseudomallei in one case . In 11 cases no bacteriological diagnosis could be made . Two patients with adult group B streptococcal meningitis had predisposing conditions for infection . One patient died before a definite diagnosis could be established . A ten year review of records revealed one previous case of adult group B streptococcal meningitis in a patient with multiple risk factors . CONCLUSIONS: An increase of group B streptococcal meningitis has occurred among adults admitted to two major hospitals in two Southeast Asian cities . In the majority of cases there were no identifiable predisposing conditions . The cause of this increase of group B streptococcal remains unclear.

Aust N Z J Med, 2000 Aug, 30(4), 441 - 9
The impact of penicillin resistance on the outcome of invasive Streptococcus pneumoniae infection in children; Rowland KE et al.; BACKGROUND: Invasive infections caused by Streptococcus pneumoniae with reduced susceptibility to penicillin are increasing in prevalence in Australia . AIMS: To determine the impact of reduced susceptibility of S . pneumoniae to penicillin on morbidity, mortality and treatment of invasive infection . METHODS: Retrospective case note review of children with invasive S . pneumoniae infection over a 26 month period . Penicillin minimum inhibitory concentrations (MIC) were determined by E test . Primary clinical outcome measures included days to defervescence, duration of hospital stay, complication rates and mortality . The secondary outcome of financial cost was examined . Comparisons between outcomes of patients with infections caused by susceptible and non-susceptible strains were performed with Student's t test, Pearson chi2, Mann-Whitney U tests and multiple logistic regression . RESULTS: Sixty-eight episodes of invasive pneumococcal disease were reviewed: 14 isolates (21.1%) had reduced susceptibility or resistance to penicillin (PNSSP, MIC 0.125 mg/L-1.5 mg/L) . Ten patients had meningitis, 21 had pneumonia, 22 had bacteraemia with another focus and 15 had bacteraemia without an obvious focus . PNSSP were more common in patients with meningitis and pneumonia . No patients died . Overall, patients with infections caused by PNSSP had significantly longer hospitalisation and longer time to defervescence . Complication rates were not significantly different between groups . Outcome differences were no longer significant when meningitis patients were excluded from the analysis . The PNSSP group received more expensive intravenous antibiotics and their infections were significantly more costly to treat . CONCLUSIONS: Infections with penicillin non-susceptible S . pneumoniae are associated with higher morbidity than infections with penicillin susceptible strains, and treatment of these infections is more expensive, due to higher drug costs and longer hospital stay.

Clin Infect Dis, 2000 Aug, 31 Suppl 2, S45 - 50
Pharmacodynamics of gatifloxacin in experimental models of pneumococcal meningitis; McCracken GH Jr; The alarming increase of bacterial resistance has had a serious impact on treatment practices for patients with meningitis and has prompted investigation of other possibly effective antibiotic regimens with agents, such as gatifloxacin and trovafloxacin, that have excellent activity against Streptococcus pneumoniae . The use of fluoroquinolones in children has been limited by studies that report chondrotoxicity in young animals . Gatifloxacin, a new fluoroquinolone, was recently tested in a rabbit model of cephalosporin-resistant pneumococcal meningitis . In these studies, animals were infected with a ceftriaxone-resistant (minimal inhibitory concentration {MIC}, 4 microg/mL; minimal bactericidal concentration {MBC}, 4 microg/mL) and gatifloxacin-susceptible (MIC, 0.125 microg/mL; MBC, 0.25 microg/mL) strain of S . pneumoniae and were treated with either a single- or divided-dose regimen of gatifloxacin . Results from these studies are reviewed and compared with data from other studies that used a similar rabbit model of pneumococcal meningitis . Overall, it was found that the bacteriologic efficacy of gatifloxacin against S . pneumoniae was as effective as that of conventional regimens . Bactericidal activity of gatifloxacin was correlated with the area under the time-concentration curve-to-MBC ratio; maximal activity was achieved when gatifloxacin concentrations exceeded the MBC for the entire dosing interval.

Clin Infect Dis, 2000 Aug, 31 Suppl 2, S29 - 34
Microbiological and pharmacodynamic considerations in the treatment of infection due to antimicrobial-resistant Streptococcus pneumoniae; Appelbaum PC; The incidence of antimicrobial-resistant strains of Streptococcus pneumoniae has increased alarmingly in recent years . The problem is exacerbated by the global spread of resistant organisms . Currently, the incidence of penicillin-resistant pneumococci isolated from clinical specimens in the United States is > or = 35% . For empirical oral treatment of community-acquired respiratory infections, 3 choices are available: beta-lactam agents, macrolides, and fluoroquinolones . In considering the therapeutic efficacy of these agents, it is essential to also take pharmacokinetic and pharmacodynamic (PK/PD) factors into account . Many drugs are effective against penicillin-susceptible strains . However, the higher the minimum inhibitory concentration of penicillin, the more likely that cross-resistance to beta-lactam agents and macrolides will occur . Currently, the incidence of fluoroquinolone-resistant pneumococci is low; it is proposed that adequate dosing based on the PK/PD properties of fluoroquinolones may help reduce the emergence of resistant organisms . Prudent use of all antimicrobials is essential to decrease the emergence of strains resistant to these agents.

Drugs Aging, 2000 Aug, 17(2), 93 - 105
Community-acquired pneumonia in the elderly: a practical guide to treatment; Lieberman D et al.; The incidence of community-acquired pneumonia (CAP), an infectious disease, sharply increases among the elderly and the main risk factor for CAP in this age group is chronic comorbidity . The use of the term CAP in the elderly population should be reserved for pneumonia acquired outside of the nursing home setting, since nursing home-acquired pneumonia differs from CAP in terms of its aetiology and clinical manifestations . The main aetiology for CAP is Streptococcus pneumoniae, but atypical pathogens also play an important role as causative agents . The clinical presentations of CAP in the elderly can be different from those in younger patients, and therefore it is important to be aware of and familiar with these differences to avoid unnecessary delays in reaching the correct diagnosis . Imaging is essential to diagnose CAP and to assess its severity . Clinical and laboratory indices can be used to identify elderly patients with CAP who are at low risk for mortality and who can be treated as outpatients . The decision not to hospitalise elderly patients with CAP is contingent on a good clinical condition and the existence of home support systems . The aetiology of CAP cannot be determined on the basis of clinical manifestations, imaging or routine laboratory test results, and the initial antibiotic therapy for elderly patients with CAP should be empirical, based on accepted guidelines . In the light of developments in recent years, elderly patients with CAP, except those who are severely ill, can be treated empirically with once-daily antibiotic monotherapy in the initial phase, using a third-generation fluoroquinolone preparation, such as sparfloxacin, levofloxacin or moxifloxacin, or a new macrolide such as clarithromycin, azithromycin or dirithromycin . In addition to antibiotic therapy, it is critically important to identify and treat the physiological disturbances that accompany CAP as well as decompensation of chronic comorbid conditions . As soon as the patient's condition permits, oral antibiotic therapy should replace intravenous therapy and early discharge from the hospital should be considered . Since influenza and pneumococcus immunisation can reduce morbidity and mortality from CAP, it is important to implement regular immunisation programmes in the primary care setting.

J Periodontal Res, 2000 Aug, 35(4), 186 - 93
Effects of areca nut extracts on the functions of human neutrophils in vitro; Hung SL et al.; Aqueous extracts of ripe areca nut without husk (ripe ANE) and fresh and tender areca nut with husk (tender ANE) were examined for their effects on the defensive functions of human neutrophils . Exposure of peripheral blood neutrophils to ripe ANE and tender ANE inhibited their bactericidal activity against oral pathogens, including Actinobacillus actinomycetemcomitans and Streptococcus mutans, in a dose-dependent manner . At the concentrations tested, ripe and tender ANEs did not significantly affect the viability of neutrophils as verified by their ability to exclude trypan blue dye . However, both ANEs inhibited the production of bactericidal superoxide anion by neutrophils as measured by cytochrome c reduction . Moreover, the ripe ANE inhibited neutrophils more effectively than did tender ANE . Arecoline, a major alkaloid of areca nut, only exhibited an inhibitory effect on the functions of neutrophils when high concentrations were used . Therefore, arecoline could not be used to explain the inhibitory effects observed for ANEs . In conclusion, our results demonstrated that ripe and tender ANEs reduced the antibacterial activity and the superoxide anion production of neutrophils . This effect may contribute to a less efficient elimination of bacteria from the periodontal environment . Inhibition of the antimicrobial functions of neutrophils may alter the microbial ecology of the oral cavity, and this may be one possible mechanism by which areca nut compromises the oral health of users of areca nut products.

J Hepatobiliary Pancreat Surg, 2000, 7(2), 231 - 5
Hepatic abscess as a complication of the sump syndrome; Hiura A et al.; We report a case of hepatic abscess associated with the sump syndrome . The patient was a 66-year-old woman who had undergone cholecystectomy and side-to-side choledochoduodenostomy for a common bile duct (CBD) stone in 1983, and who presented with fever and right lower chest pain . A hepatic abscess was diagnosed; after it was drained, percutaneous transhepatic biliary drainage was performed . Bacteriological studies revealed the presence of Bacteroides fragilis and Streptococcus intermedius in the pus in the hepatic abscess cavity, and Klebsiella pneumoniae and Pseudomonas aeruginosa in the bile . The hepatic abscess and cholangitis rapidly resolved in response to two drainage procedures . At surgery, simple closure of the anastomosis was performed, because free drainage was observed from the distal CBD into the duodenum, despite the existence of a periampullary diverticulum.

An Med Interna, 2000 Jul, 17(7), 356 - 60
{Infective endocarditis in intravenous drug users . Study of 34 cases}; Espinosa Parra FJ et al.; OBJECTIVE: Infective endocarditis (IE) in injection drug users (IDU) have a special etiologic, epidemiological and clinical characteristics different to IE in the general population . The clinical and evolutive features of a group of IE in IVD are reported . METHODS: A retrospective analysis was made of 34 episodes (24 patients) of IE in IDU in the Catagena Area (Murcia, Sapin) . RESULTS: A total 34 episodes, 18 was males (75%) and 6 (25%) females with a age media of 26.1 years (DE, 4.3) . Eighty-four percents were infected with human immunodeficiency virus . The location of IE was right-side in 26 (73%), left-side in 7 cases (18%) and right-left in one (2%) . Staphylocococcus aureus was isolated in 31 cases (91%), it was meticillin-resistant in 4 cases (13%); Pseudomonas aeruginosa, and Streptococcus equisimilis was isolated in one case each . Fever was present in 33 patients (97%) and more than half were cough, pleuritic chest pain and expectoration . Twenty-five patients with right IE has chest X-ray abnormal, specially nodules-infiltrates pulmonary . Vegetations were not observe in 7 (21%) occasions by transthoracic echocardiography . In six of 8 patients with left-side IE present a cerebri embolisms . Two patients with left IE death (21%) . The rate of successful therapy in the right-side IE treated during 2 or 4 weeks were 100% . CONCLUSIONS: The IE in IDU is a entity produced mainly by S . aureus, affect preferentially a right-side cavities and the prognosis is generally good.

Curr Gastroenterol Rep, 2000 Aug, 2(4), 277 - 82
New developments and concepts in antimicrobial therapy for intra-abdominal infections; Younes Z et al.; Antimicrobial therapy plays an integral role in the management of intra-abdominal infections . Recent developments include increased prevalence of antimicrobial resistance (eg, Streptococcus pneumoniae and Enterococcus species) coupled with general decline in the antimicrobial susceptibility of anaerobes and gram-negative organisms, new antibiotics and dosing regimens, and better understanding of the role of various microbial pathogens and of prophylactic antimicrobial agents . Therapeutic approaches to intra-abdominal infections, such as the various forms of peritonitis, cholecystitis, cholangitis, and diverticulitis, are reviewed here . Specific recommendations for antimicrobial therapy in various clinical settings are provided, with special emphasis on recent trends and developments that reflect changes in understanding or therapy.

Dentomaxillofac Radiol, 2000 Sep, 29(5), 286 - 90
Experimental induction of rheumatoid arthritis in temporomandibular joint of the guinea pig: a clinical and radiographic study; al-Mobireek AF et al.; OBJECTIVE: To correlate the clinical and radiographic changes at different stages of experimentally-induced rheumatoid arthritis (RA) of the TMJ . METHODS: Forty eight adult male guinea pigs, aged 4-6 months, were divided into two groups . Arthritis was induced in the experimental animals by intraperitoneal injection of heat-inactivated group A Streptococcus pyogenes . Four animals from each group were sacrificed and examined clinically and radiographically at intervals of 48 h and 1, 2, 4, 6 and 8 weeks . RESULTS: The main clinical findings were stiffness, crepitation and reduction in mouth opening . Radiographically, the main features were condylar erosion, flattening and sclerosis subcortical cyst formation . CONCLUSION: RA passes through stages that can be correlated clinically and radiographically . Both the clinical and radiographic manifestations in this experimental model are comparable with those previously reported in the small joints of humans.

J Antimicrob Chemother, 2000 Sep, 46(3), 471 - 4
In vitro and in vivo antibacterial activities of a new injectable carbapenem, S-4661, against gynaecological pathogens; Mikamo H et al.; Carbapenems are often used to treat infections in obstetrics and gynaecology because of their activity against anaerobes . S-4661, a new injectable carbapenem antibiotic, has favourable pharmacokinetic properties and is not hydrolysed by dehydropeptidase I . We investigated the in vitro and in vivo antibacterial activities of S-4661 against strains of Streptococcus agalactiae, Escherichia coli, Peptostreptococcus magnus, Bacteroides fragilis and Prevotella bivia, which are major pathogens in the fields of obstetrics and gynaecology . The MIC(50) and MIC(90) of S-4661 for these strains were 0.25 and 1 mg/L, respectively . The in vivo efficacy of S-4661 was evaluated in a rat model of intrauterine infection, namely pyometra caused by E . coli and B . fragilis . The accumulation of neutrophils in the uterus in the S-4661-treated group was less marked and the number of bacteria significantly lower than those in the untreated group . These results suggest that S-4661 may be useful for treating polymicrobial infections in the fields of obstetrics and gynaecology.

J Infect Dis, 2000 Oct, 182(4), 1153 - 60 Epub 2000 Sep 01.
Carriage of internationally spread clones of Streptococcus pneumoniae with unusual drug resistance patterns in children attending day care centers in Lisbon, Portugal; Sa-Leao R et al.; Over half (259/503) of drug-resistant (DR) pneumococci colonizing healthy children attending day care centers in Lisbon were identified by molecular typing methods as representatives of several internationally spread clones . These included the 2 penicillin-resistant pandemic Spanish/USA and French/Spanish clones (21% of all DR pneumococci) and 5 new lineages with unusual antibiotypes (accounting for an additional 30% of all DR pneumococci) . The most characteristic feature of the latter group was the high frequency of resistance to macrolides and tetracycline and very low or no resistance to penicillin . These observations provide support for the notion that the nasopharyngeal flora of children in day care centers may be a global reservoir of worldwide prevalent strains of DR pneumococci.

J Infect Dis, 2000 Oct, 182(4), 1146 - 52 Epub 2000 Sep 05.
Natural development of antibodies to pneumococcal surface protein A, pneumococcal surface adhesin A, and pneumolysin in relation to pneumococcal carriage and acute otitis media; Rapola S et al.; Pneumococcal surface protein A (PspA), pneumococcal surface adhesin A (PsaA), and pneumolysin (Ply) are common to virtually all Streptococcus pneumoniae isolates . They are immunogenic and protective against pneumococcal challenge in animals and are the major candidates for a protein-based pneumococcal vaccine for humans . However, little is known of the natural development of antibodies to these proteins in humans . The objective of this study was to evaluate the natural development of antibodies to PspA, PsaA, and Ply in relation to pneumococcal infection and carriage in young children . Serum antibodies to these proteins were measured by EIA in children at ages 6, 12, 18, and 24 months and in their mothers . All age groups were capable of producing antibodies to the 3 proteins . The antibody concentrations increased with age and were strongly associated with pneumococcal exposure, whether by carriage or infection (acute otitis media).

J Infect Dis, 2000 Oct, 182(4), 1139 - 45 Epub 2000 Aug 31.
Pneumococcal capsular polysaccharide-specific IgA triggers efficient neutrophil effector functions via FcalphaRI (CD89); van der Pol W et al.; Specific anti-capsular polysaccharide IgG is believed to be important for protection against infection by Streptococcus pneumoniae . Significant IgA responses have been observed after vaccination with pneumococcal vaccines, but the role of this isotype in anti-pneumococcal host defense is unclear . Here, it is shown that purified serum IgA specific for pneumococcal capsular polysaccharides can initiate efficient cellular effector functions, such as phagocytosis, via interaction with the myeloid IgA receptor, FcalphaRI (CD89) . The efficiency of FcalphaR-triggered granulocyte effector functions was comparable to that of FcgammaRIIa (CD32), as shown in experiments with bispecific antibodies . These results support a role for polysaccharide-specific IgA in antipneumococcal cellular effector function and suggest that FcalphaRI represents an important leukocyte receptor for immunity against S . pneumoniae.

J Infect Dis, 2000 Oct, 182(4), 1129 - 38 Epub 2000 Sep 08.
Use of capsular polysaccharide-tetanus toxoid conjugate vaccine for type II group B Streptococcus in healthy women; Baker CJ et al.; An estimated 15% of invasive group B streptococcal (GBS) disease is caused by type II capsular polysaccharide (II CPS) . In developing a pentavalent vaccine for the prevention of GBS infections, individual GBS CPSs have been coupled to tetanus toxoid (TT) to prepare vaccines with enhanced immunogenicity . Type II GBS (GBS II) vaccine was created by direct, covalent coupling of II CPS to TT by reductive amination . In 2 clinical trials, 75 healthy nonpregnant women 18-45 years old were randomized to receive II CPS-TT (II-TT) conjugate (dose range, 3.6-57 microg of CPS component) or uncoupled II CPS vaccine . Both vaccines were well tolerated . II CPS-specific IgG serum concentrations (as well as IgM and IgA) peaked 2 weeks after immunization, being significantly higher in recipients of conjugated vaccine than in recipients of uncoupled CPS . Immunological responses to conjugate were dose dependent and correlated with opsonophagocytosis in vitro . These results support inclusion of II-TT conjugate when preparing a multivalent GBS vaccine.

J Infect Dis, 2000 Oct, 182(4), 1117 - 28 Epub 2000 Sep 08.
Molecular epidemiology of nga and NAD glycohydrolase/ADP-ribosyltransferase activity among Streptococcus pyogenes causing streptococcal toxic shock syndrome; Stevens DL et al.; Severe invasive group A streptococcal (GAS) infections emerged in the late 1980s, yet no single virulence factor has been common to all isolates from infected patients . A strong association was recently found between isolates of such cases (regardless of M type) and the production of NAD glycohydrolase (NADase) . Of interest, all M-1 strains isolated after 1988 were positive for NADase, whereas virtually all M-1 GAS were previously negative for NADase . Genetic analysis demonstrated that GAS isolates were >96% identical in nga and >99% identical in their upstream regulatory sequences . Furthermore, because NADase-negative strains did not produce immunoreactive NADase, we concluded that additional regulatory element(s) control NADase production . NADase purified from GAS altered neutrophil-directed migration and chemiluminescence responses and had potent ADP-ribosyltransferase activity . In summary, the temporal relationship of NADase expression, alone or with other streptococcal virulence factors, may contribute to the pathogenesis of invasive GAS infections.

Am J Rhinol, 2000 Jul-Aug, 14(4), 233 - 40
Effects of fibrin sealant-containing antibiotics in a rabbit model of chronic sinusitis; Schlosser RJ et al.; Postoperative complications of sinus surgery include bleeding, infection, and synechiae . Improved subjective outcomes in humans treated with fibrin sealant (FS) after endoscopic sinus surgery (ESS) have been reported . Streptococcus pneumoniae was used to initiate chronic sinusitis in occluded rabbit sinuses in order to evaluate the role of FS in mucosal healing . Six weeks later, all animals had maxillary antrostomies . Homologous FS-containing ciprofloxicin (100 mg/mL) and clindamycin (15 mg/mL) was applied topically to treatment rabbits (n = 9) . Control rabbits (n = 10) received no antibiotics . Two weeks into the recovery phase after antrostomies, all animals were re-examined . Mucociliary transport velocity (mean +/- standard deviation in mm/minute) was measured in all sinuses (n = 38) during healthy (100% measurable, 13.82 +/- 4.16), infected (18% measurable, 4.74 +/- 0.42), and recovery phases (5% measurable, 6.30 +/- 4.67) . In both groups, mucopurulent discharge was present in the majority of sinuses (control group 18/20, FS group 16/18) . In addition, there was no significant difference in the recovery phase between the two groups when comparing changes in the size of antrostomies, light microscopy, or culture clearance . Scanning electron microscopy did suggest a possible improvement in ciliary regeneration in the FS group . Application of FS-containing antibiotics did not appear to improve healing after ESS in our rabbit model of chronic sinusitis.

Am J Vet Res, 2000 Sep, 61(9), 1092 - 8
Herd characteristics and management practices associated with bulk-tank somatic cell counts in herds in official Dairy Herd Improvement Association programs in Ohio; Khaitsa ML et al.; OBJECTIVE: To identify herd characteristics and management practices associated with bulk-tank somatic cell counts (BTSCC) in dairy herds in Ohio enrolled in official Dairy Herd Improvement Association (DHIA) programs . SAMPLE POPULATION: 186 dairies in Ohio . PROCEDURE: All herds in official DHIA programs in 9 counties were asked to participate . Extensive information regarding herd characteristics and management practices was obtained, using a standardized questionnaire . Bulk-tank milk samples were requested from all participating herds for bacterial culture . Official DHIA test-day records for January 1997 were obtained from all herds enrolled in official DHIA programs in the 9 counties . Potential associations were identified, using multivariable ANOVA . RESULTS: Participation was 186 of 479 (39%) herds . Streptococcus agalactiae and Mycoplasma spp were not isolated from bulk-tank milk samples . Staphylococcus aureus was isolated from 64 of 172 (37%) of the herds . The BTSCC were inversely associated with peak daily milk production, postmilking teat disinfection, percentage of eligible cows in the herd detected in estrus, and directly related to the extent to which BTSCC was perceived as a herd problem during the preceding 2 years . Type of housing for nonlactating cows and product used for treatment of nonlactating cows also were significantly associated with BTSCC . CONCLUSIONS AND CLINICAL RELEVANCE: Consideration of herd characteristics and implementation of management practices associated with BTSCC could result in increased milk yield and production of milk with lower BTSCC.

Pediatr Nephrol, 2000 Sep, 14(10-11), 985 - 9
Peripheral gangrene complicating idiopathic and recessive hemolytic uremic syndromes; Kaplan BS et al.; Three patients with hemolytic uremic syndrome (HUS) developed peripheral gangrene . Bilateral carotid artery thromboses occurred in one of these patients after recovery from HUS . One patient had a long history of juvenile rheumatoid arthritis . In the second patient, a flu-like illness preceded the onset of HUS . The third was one of two sisters, with the HUS appearing more than 1 year apart . None had evidence of disseminated intravascular coagulation or infection with Streptococcus pneumoniae . The patient with rheumatoid arthritis had renal cortical necrosis but recovered moderate renal function after treatment with dialysis and plasmapheresis for 6 months . The child with a genetic form of HUS died of renal failure and had massive cortical necrosis and vascular thrombosis at autopsy . This is the first report of peripheral gangrene in children with idiopathic HUS and autosomal recessive HUS.

Diagn Microbiol Infect Dis, 2000 Aug, 37(4), 285 - 7
Comparison of four methods for identifying Streptococcus pneumoniae; Chandler LJ et al.; Four methods (bile solubility, optochin, latex agglutination, and DNA probe) were compared for identification of clinical isolates of Streptococcus pneumoniae . Of 209 isolates tested, 151 (Group I) were selected based on typical colony morphology of S . pneumoniae, while 58 (Group II) were selected on the basis of alpha-hemolysis alone . Using the DNA probe as a reference method, 141 isolates from Group I and 10 from Group II were identified as S . pneumoniae . The optochin disk test and the latex agglutination test both exhibited a 100% sensitivity and specificity for Group I isolates; bile solubility identified all but 1 isolate in this group . For Group II isolates, the sensitivity and specificity of optochin testing was 100%, 80 and 94% for latex and 80 and 100% for bile . The results of this study indicate that all methods tested give reliable results for isolates with typical colony morphology of S . pneumoniae . Bile solubility and latex may not be as reliable when testing alpha-hemolytic colonies without colony morphology typical S . pneumoniae.

Diagn Microbiol Infect Dis, 2000 Aug, 37(4), 261 - 4
Activity of gatifloxacin compared to those of seven agents against bacteria recovered from outpatients with respiratory tract infection; Smayevsky J et al.; The in vitro activity of gatifloxacin and levofloxacin, ciprofloxacin, penicillin, ampicillin, ampicillin-sulbactam, ceftriaxone and clarithromycin was evaluated against 173 S . pneumoniae strains (128, penicillin-susceptible strains; 32, intermediate penicillin- resistant strains and 13, penicillin-resistant strains), 163 H . influenzae strains (128, beta-lactamase non-producer; 35, beta-lactamase producers), 111 M . catarrhalis (9, beta-lactamase non-producer; 102, beta-lactamase producers), 95 Streptococcus pyogenes and 116 S . aureus strains (96, methicillin-susceptible; 20, methicillin-resistant) recovered from outpatients with respiratory tract infection.Based upon the MICs at which 50% and 90% of the isolates were inhibited we concluded that gatifloxacin proved to be the most active antibiotic against respiratory pathogens, including all the penicillin-resistant pneumococci and H . influenzae or M . catarrhalis producing beta-lactamase . Furthermore, their MICs against S . pneumoniae and methicillin-resistant S . aureus were lower than those of levofloxacin and ciprofloxacin.Therefore, this new fluoroquinolone displayed in vitro features that make it suitable for treating community-acquired respiratory tract infections.

Vet Microbiol, 2000 Oct 1, 76(3), 259 - 72
The pathogenesis of the meningitis caused by Streptococcus suis: the unresolved questions; Gottschalk M et al.; Streptococcus suis is one of the most important swine pathogens world-wide . Among the serotypes described, type 2 is the serotype most frequently associated with disease . Despite increasing research in recent years, knowledge of virulence factors and the pathogenesis of the infection remain limited . This review discusses the currently available information on S . suis serotype 2 virulence factors and the pathogenesis of the meningitis caused by this important bacterial species . In addition, some hypotheses on the critical steps of the infection, such as bacterial invasion from mucosal surfaces to the bloodstream, survival of bacteria in blood, and invasion from blood into the central nervous system, are presented . Finally, the role that the stimulation of the immune system of animals (inflammatory reaction) could play during infection is also discussed . A complete understanding of the cell-interacting pathways that S . suis may follow inside the host could give important insights into the progression of disease . Further studies to delineate the mechanisms through which S . suis induces meningitis will contribute to the development of potential therapies for S . suis infections.

Mol Microbiol, 2000 Sep, 37(5), 1232 - 47
Virulent aggregates of Streptococcus pyogenes are generated by homophilic protein-protein interactions; Frick IM et al.; Many strains of the important human pathogen Streptococcus pyogenes form aggregates when grown in vitro in liquid medium . The present studies demonstrate that this property is crucial for the adherence, the resistance to phagocytosis and the virulence of S . pyogenes . A conserved sequence of 19 amino acid residues (designated AHP) was identified in surface proteins of common S . pyogenes serotypes . This sequence was found to promote bacterial aggregation through homophilic protein-protein interactions between AHP-containing surface proteins of neighbouring bacteria . A synthetic AHP peptide inhibited S . pyogenes aggregation, reduced the survival of S . pyogenes in human blood and attenuated its virulence in mice . In contrast, mutant bacteria devoid of surface proteins containing AHP-related sequences did not aggregate or adhere to epithelial cells . These bacteria are also rapidly killed in human blood and show reduced virulence in mice, underlining the pathogenic significance of the AHP sequence and S . pyogenes aggregation.

Mol Microbiol, 2000 Sep, 37(5), 1159 - 71
Divergent structure of the ComQXPA quorum-sensing components: molecular basis of strain-specific communication mechanism in Bacillus subtilis; Tran LS et al.; In Bacillus subtilis, the ComQXPA quorum-sensing system controls cell density-dependent phenotypes such as the production of degradative enzymes and antibiotics and the development of genetic competence . Bacillus subtilis (natto) NAF12, a mutant defective in poly-gamma-glutamate (gamma-PGA) production, was derived from B . subtilis (natto) NAF4 by Tn917-LTV1 insertional mutagenesis . Determination of the mutant DNA sequences flanking the Tn917-LTV1 insert revealed that the insertion had inactivated comP in this mutant, indicating that gamma-PGA synthesis in B . subtilis (natto) is under the control of the ComP-ComA signal transduction system . A comparison of the amino acid sequences revealed striking variation in the primary structures of ComQ (44% identity), ComX (26%) and the sensor domain of ComP (36%) between B . subtilis (natto) NAF4 and B . subtilis 168 . In contrast, the amino acid and nucleotide sequences of the kinase domains of ComP and of the ComA response regulator share 95% and 100% identity respectively . The comP genes of NAF4 and 168 restored the impaired competence of B . subtilis BD1658 (comP:cat) and gamma-PGA production of B . subtilis (natto) NAF12 (comP:Tn917-LTV1) to only 15% of the level achieved by the respective parent comP genes . However, when introduced together with the cognate comQ and comX genes, the comP genes restored the relevant defect of the heterologous comP mutants nearly to wild-type levels . Analogous to the comCDE system of Streptococcus strains and the agrBCDE system of Staphylococcus aureus, the concerted variation in the comQXP genes appears to establish specific intercellular communication between B . subtilis strains sharing the same pheromone system.

Mol Microbiol, 2000 Sep, 37(5), 1019 - 31
Differential functionalities of amphiphilic peptide segments of the cell-septation penicillin-binding protein 3 of Escherichia coli; Marrec-Fairley M et al.; The class B M1-V577 penicillin-binding protein (PBP) 3 of Escherichia coli consists of a M1-L39 membrane anchor (bearing a cytosolic tail) that is linked via a G40-S70 intervening peptide to an R71-I236 non-catalytic module (containing the conserved motifs 1-3) itself linked via motif 4 to a D237-V577 catalytic module (containing the conserved motifs 5-7 of the penicilloyl serine transferases superfamily) . It has been proposed that during cell septation the peptidoglycan crosslinking activity of the acyl transferase module of PBP3 is regulated by the associated M1-I236 polypeptide itself in interaction with other components of the divisome . The fold adopted by the R71-V577 polypeptide of PBP3 has been modelled by reference to the corresponding R76-S634 polypeptide of the class B Streptococcus pneumoniae PBP2x . Based on these data and the results of site-directed mutagenesis of motifs 1-3 and of peptide segments of high amphiphilicity (identified from hydrophobic moment plots), the M1-I236 polypeptide of PBP3 appears to be precisely designed to work in the way proposed . The membrane anchor and the G40-S70 sequence (containing the G57-Q66 peptide segment) upstream from the non-catalytic module have the information ensuring that PBP3 undergoes proper insertion within the divisome at the cell septation site . Motif 1 and the I74-L82 overlapping peptide segment, motif 2 and the H160-G172 overlapping peptide segment, and the G188-D197 motif 3 are located at or close to the intermodule junction . They contain the information ensuring that PBP3 folds correctly and the acyl transferase catalytic centre adopts the active configuration . The E206-V217 peptide segment is exposed at the surface of the non-catalytic module . It has the information ensuring that PBP3 fulfils its cell septation activity within the fully complemented divisome.

Lett Appl Microbiol, 2000 Aug, 31(2), 174 - 7
In vitro activity of propolis against Streptococcus pyogenes; Bosio K et al.; Propolis, a multifunctional substance used by bees to maintain the safety of their hives, is popular for its therapeutic potential against some micro-organisms . Ethanolic extracts of two propolis specimens, collected from different areas within a region in the north-west of Italy, were examined to evaluate their antimicrobial activity against 46 Streptococcus pyogenes strains . By both agar dilution and agar diffusion methods, the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were </= 234 microg ml-1, corresponding to a one in 512 dilution of the 12% (w/v) extracts . One of the two propolis samples was more active and this extract was shown to be richer in the flavonoids pinocembrin and galangin using HPLC . Therefore, with a simple microbiological assay technique, in particular the agar dilution method, it was possible to standardize the analysis of propolis samples to identify the quality parameters of this natural product before use for medical treatment.

Med J Malaysia, 1998 Dec, 53(4), 442 - 5
Fatal early-onset neonatal sepsis due to Streptococcus pneumoniae; Nallusamy R; Two cases of invasive early-onset neonatal pneumococcal sepsis are reported . One neonate was born at term with no risk factors and the other preterm at 35 weeks . Sepsis was not detected at birth for either of these babies and diagnosis was made at the stage of severe sepsis . A fatal outcome resulted despite treatment . Pneumococcal sepsis was confirmed after death in both these cases . Although maternal carriage was not documented in either case, the ages at presentation and progression suggested perinatal acquisition of infection . Early onset neonatal pneumococcal sepsis presents similarly as early onset neonatal Group B streptococcal (GBS) sepsis . Vaginal carriage of pneumococcus is rare but the micro-organism may have a higher invasion to colonisation ratio (attack rate) than GBS . Risk factors for invasive disease are similar to GBS.

Pediatrics . 2000 Sep;106(3):E40.
Endocarditis attributable to group A beta-hemolytic streptococcus after uncomplicated varicella in a vaccinated child; Laskey AL et al.; Varicella is generally a benign, self-limited childhood illness; however, severe, life-threatening complications do occur . A live, attenuated vaccine exists to prevent this illness, but controversy remains concerning the need to vaccinate children for what is generally a benign, self-limited disease, although more states are currently recommending this vaccine . We report a previously healthy 3-year-old who developed varicella 6 months after vaccination with no apparent skin superinfections, who subsequently developed group A beta-hemolytic streptococcus (GABHS) bacteremia resulting in endocarditis of a normal heart valve . We are unaware of previous reports of endocarditis related to GABHS after varicella . After developing a harsh, diastolic murmur that led to an echocardiogram, aortic valve endocarditis was diagnosed . A 6-week course of intravenous penicillin G was administered . Two weeks after the initiation of therapy, the diastolic murmur was harsher, and echocardiography revealed a large vegetation on the posterior leaflet of the aortic valve, with severe aortic insufficiency and a dilated left ventricle . The patient subsequently developed congestive heart failure requiring readmission and aggressive management . One month after the initial echocardiogram, a repeat examination revealed worsening aortic regurgitation and mitral regurgitation . The patient received an additional 4 weeks of intravenous penicillin and gentamicin followed by aortic valve replacement using the Ross procedure . Our patient, the first reported case of bacteremia and endocarditis from GABHS after varicella, illustrates the need for the health care practitioner to consider both common and life-threatening complications in patients with varicella . While cellulitis, encephalitis, and septic arthritis may be readily apparent on physical examination and commonly recognized complications of varicella, the possibility of bacteremia without an obvious skin superinfection should also be entertained . The case we report is unique in that the patient had normal immune function, had been previously vaccinated, and developed a rare complication of varicella-endocarditis-in a structurally normal heart with a previously unreported pathogen . Although a child may have been vaccinated against varicella, the chance of contracting the virus still exists and parents should be informed of this risk . group A beta-hemolytic streptococcus, endocarditis, varicella, Varivax, complications of varicella.

Infect Dis Obstet Gynecol, 2000, 8(3-4), 143 - 50
Liberal diagnosis and treatment of intrauterine infection reduces early-onset neonatal group B streptococcal infection but not sepsis by other pathogens; Wolf H et al.; OBJECTIVE: Comparison of the incidence and case fatality of early-onset group B streptococcus sepsis and sepsis caused by other pathogens in neonates after change of management of intrauterine infection . METHODS: All infants delivered from 1988 through 1997 at a gestational age > or = 24 weeks with a birth weight > or = 500 gram without lethal congenital abnormalities were eligible for inclusion . Infants delivered by cesarean section before the onset of labor or rupture of membranes were excluded . During the first period (1988-1991) intrauterine infection was diagnosed by a temperature > 38 degrees C, during the second period (1992-1997) this diagnosis was made at a lower temperature (> or = 37.8 degrees C) or by fetal tachycardia > or = 160/min . Treatment of intrauterine infection was similar during both periods with 3 x 2 gram amoxicillin and 1 x 240 mg gentamicin every 24 hours intravenously during labor . Prophylactic treatment during labor was only given to women with a history of an earlier infant with early-onset group B streptococcus sepsis . RESULTS: During the first period 6,103 infants were included, during the second period 8,504 . Intrauterine infection was diagnosed and treated more often in the second period (7.1% vs . 2.6%) . The incidence of early-onset group B streptococcus sepsis was significantly lower in the second period than in the first period {0.2% vs . 0.4%; OR 0.5 (0.3-0.9)} and survival without disability higher {80% vs . 52%; OR 4.5 (1.4-16.5)} . However, in both periods the overall incidence of neonatal sepsis (3.6% vs . 3.5%) and overall mortality because of sepsis (14.3% vs.13.1%) were similar . CONCLUSIONS: Although the early detection of clinical signs of intrauterine infection might have been effective for the prevention of serious sequelae of early-onset group B streptococcus sepsis the overall incidence and mortality from neonatal sepsis remained unchanged . Evaluation of preventive measures for early-onset group B streptococcus sepsis should always take the incidence of neonatal sepsis caused by other pathogens into account.

Med J Malaysia, 1996 Mar, 51(1), 134 - 6
Necrotizing fasciitis; Zubaidah AW et al.; A 31-year-old Pakistani man was admitted to hospital after sustaining a Grade I compound fracture of the mid-shaft of the left tibia and fibula following a motor vehicle accident . He developed septicaemic shock, acute renal failure and Group A streptococcal necrotizing fasciitis of the left leg . The patient underwent an above knee amputation followed by disarticulation of the left hip with extensive debridement . He was treated with benzylpenicillin, vancomycin, inotropes and continuous haemodialysis and survived without further sequelae . Subsequently, skin grafting was done over the wound site . This case highlights the role of Group A streptococcus as a cause of this rare and life-threatening infection.

J Biol Chem, 2000 Nov 24, 275(47), 37257 - 63
Hic, a novel surface protein of Streptococcus pneumoniae that interferes with complement function; Janulczyk R et al.; The important human pathogen Streptococcus pneumoniae was found to absorb factor H, an inhibitor of complement, from human plasma . We identified the gene encoding a novel surface protein, factor H-binding inhibitor of complement (Hic), in the pspC locus of type 3 pneumococci . Unlike PspC proteins in other serotypes, Hic is anchored to the cell wall by means of an LPXTG motif, and the overall sequence homology to various PspC proteins is low . However, the NH(2)-terminal region showed significant homology to the NH(2)-terminal region of several PspC proteins . A fragment of Hic, covering this homologous region, was expressed as a glutathione S-transferase (GST) fusion protein . GST:Hic(39-261) bound radiolabeled factor H and inhibited binding of factor H to pneumococci of different serotypes . Interaction kinetics between GST:Hic(39-261) and factor H were studied with surface plasmon resonance and showed a high affinity binding (K(A) = 5 x 10(7), K(D) = 2.3 x 10(-)(8)) . Mutant pneumococci lacking Hic showed no absorption of factor H in human plasma and no binding of radiolabeled factor H, suggesting that Hic is responsible for factor H-binding in type 3 pneumococci . Factor H-dependent inhibition of the alternative pathway was not diminished by the presence of GST:Hic(39-261) . In addition, an intrinsic inhibitory effect of Hic is suggested.

Appl Environ Microbiol, 2000 Sep, 66(9), 3773 - 7
Effects of pH and energy supply on activity and amount of pyruvate formate-lyase in Streptococcus bovis; Asanuma N et al.; The enzyme system of pyruvate formate-lyase (PFL) in Streptococcus bovis was investigated by isolating PFL and PFL-activating enzyme (PFL-AE) from S . bovis, flavodoxin from Escherichia coli, and chloroplasts from spinach . In this study, the PFL and PFL-AE in S . bovis were found to be similar to those in E . coli, suggesting that the activating mechanisms are similar . The optimal pH of S . bovis PFL was 7.5, which is in contrast to the optimal pH of S . bovis lactate dehydrogenase, which is 5.5 . The apparent K(m) of S . bovis PFL was 2 mM . The intermediates of glycolysis, dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde-3-phosphate (GAP), were shown to inhibit PFL activity . The concentrations of intracellular DHAP and GAP in S . bovis ranged from 1.9 mM to less than 0.1 mM and from 0.6 mM to less than 0.05 mM, respectively, depending on the energy supply . The wide variations in DHAP and GAP levels indicated that PFL activity is allosterically regulated by these triose phosphates in vivo . The amount of PFL protein, as determined by Western blot analysis with polyclonal antibody, changed in parallel with the level of pfl-mRNA, responding to the culture conditions . These observations confirm that PFL synthesis is regulated at the transcriptional level and support the hypothesis that S . bovis shifts the fermentation pathway from acetate, formate, and ethanol production to lactate production when the pH is low and when excess energy is supplied.

J Med Microbiol, 2000 Sep, 49(9), 841 - 4
The bactericidal activity of gemifloxacin (SB-265805); Morrissey I et al.; The bactericidal activity and mechanisms of action of the new fluoroquinolone gemifloxacin were investigated against the laboratory strains Escherichia coli KL16, Staphylococcus aureus E3T and Streptococcus pneumoniae C3LN4 . Gemifloxacin was found to be highly bactericidal against these bacteria, producing a biphasic dose-response curve typical of the fluoroquinolones . This novel fluoroquinolone was more bactericidal than all other fluoroquinolones so far tested (ciprofloxacin, ofloxacin, enoxacin, lomefloxacin, levofloxacin, clinafloxacin, trovafloxacin, DV-7751 and sitafloxacin) against S . aureus and was more bactericidal than most other fluoroquinolones against E . coli or Str . pneumoniae . These data show gemifloxacin to be an improved member of the fluoroquinolone class of antibacterial agents.

J Med Microbiol, 2000 Sep, 49(9), 817 - 22
Profiling of bacterial flora in gastric biopsies from patients with Helicobacter pylori-associated gastritis and histologically normal control individuals by temperature gradient gel electrophoresis and 16S rDNA sequence analysis; Monstein HJ et al.; The aim of this study was to establish bacterial profiles in gastric biopsy specimens from patients with Helicobacter pylori-associated gastritis by means of temporal temperature gradient gel electrophoresis (TTGE) of PCR-amplified 16S rDNA fragments . Specimens from eight patients with asymptomatic gastritis and five histologically normal controls revealed a Helicobacter-specific band in the TTGE profile with increased amounts of Helicobacter-specific DNA in the biopsies from most of the gastritis patients . DNA from other genera including Enterococcus, Pseudomonas, Streptococcus, Staphylococcus and Stomatococcus was also found in the stomach . In the absence of gastric inflammation, Helicobacter spp . appeared to be part of a complex, presumably indigenous microbial flora found in the biopsy specimens from the stomach.

Chemotherapy, 2000 Sep-Oct, 46(5), 303 - 8
Time-kill studies of antimicrobial combinations including cefotaxime, ceftriaxone, vancomycin and meropenem against cephalosporin-resistant Streptococcus pneumoniae; Kim BN et al.; BACKGROUND: Resistance of Streptococcus pneumoniae to penicillin is now widespread and rapidly increasing all over the world . This has led to the critical need for alternative antimicrobial therapy . METHODS: To assess the activities of antimicrobial combinations, including cefotaxime, ceftriaxone, vancomycin and meropenem, time-kill studies were conducted against five strains of penicillin- and cephalosporin-resistant S . pneumoniae at clinically achievable antimicrobial concentrations in cerebrospinal fluid . RESULTS: Combinations of an extended-spectrum cephalosporin with vancomycin were not synergistic . Meropenem had a comparable bactericidal activity to those combinations, and its killing activity was not affected by the addition of cefotaxime, ceftriaxone or vancomycin . CONCLUSIONS: It is suggested that meropenem could be an effective alternative for the treatment of penicillin- and cephalosporin-resistant pneumococcal meningitis . However, more clinical data are required before it can be recommended as an effective antimicrobial agent for such cases .

Anal Biochem, 2000 Sep 10, 284(2), 240 - 6
Deacylation kinetics analysis of Streptococcus pneumoniae penicillin-binding protein 2x mutants resistant to beta-lactam antibiotics using electrospray ionization- mass spectrometry; Di Guilmi AM et al.; Penicillin-binding proteins (PBPs) catalyze the transpeptidase reaction involved in peptidoglycan synthesis and are covalently inhibited by the beta-lactam antibiotics . In a previous work we have focused on acylation efficiency measurements of various Streptococcus pneumoniae PBP2x* mutants to study the molecular determinants of resistance to beta-lactams . In the present paper we have developed a method to improve an accurate determination of the deacylation rate constant using electrospray ionization-mass spectrometry . This method is adaptable to the analysis of deacylation of any beta-lactam . Compared to the fluorographic technique, the ESI-MS method is insensitive to variations in the concentration of functional proteins and is therefore more reliable . We have established that the resistance of PBPs to beta-lactams is mostly due to a decrease of the acylation efficiency with only marginal effects on the deacylation rates .

Ann Otol Rhinol Laryngol Suppl, 2000 Aug, 183, 1 - 12
Controversies in the medical management of persistent and recurrent acute otitis media . Recommendations of a clinical advisory committee; Pichichero ME et al.; Streptococcus pneumoniae is the predominant bacterial pathogen associated with acute otitis media (AOM), causing an estimated 7 million cases annually in the United States . Bacterial resistance should be considered when selecting an antimicrobial agent for otitis media . Significant increases in drug-resistant S pneumoniae are documented worldwide, and less than 50% of S pneumoniae strains are fully susceptible to penicillin in some regions of the United States . Although amoxicillin is recommended for uncomplicated AOM, treatment guidelines should be flexible and adaptable, taking into consideration local and regional susceptibility patterns, the age of the patient, the frequency of prior infections, and the response to prior therapy . Resistant organisms are more prevalent in children younger than 2 years of age and in those who have recurrent or persistent AOM . Overdiagnosing AOM, selecting inappropriate empiric therapy, or both, leads to overuse and misuse of antibiotics and causes increased drug resistance . This article reviews persistent and recurrent AOM and discusses the pitfalls of diagnosis and the practical limitations of current treatment recommendations.

Clin Ther, 2000 Mar, 22(3), 281 - 94; discussion 265
Clarithromycin in the management of community-acquired pneumonia; McCarty JM; OBJECTIVE: To review the epidemiology and diagnosis of community-acquired pneumonia (CAP) and examine factors that influence the choice of empiric antimicrobial therapy . BACKGROUND: CAP remains a common disease with substantial associated morbidity and mortality . Outpatient management of patients with CAP has become increasingly complex because of the availability of newer antimicrobial agents, evolving patterns of resistance, and the increasing recognition of atypical pathogens . Although Streptococcus pneumoniae remains a commonly encountered pathogen, the development and increasing prevalence of antibiotic resistance has become an area of concern, especially in outpatients . The newer macrolide antimicrobial drugs-clarithromycin and azithromycin-are effective against commonly encountered pathogens, are well tolerated, and have an established tolerability profile, although the low serum levels achieved by azithromycin hinder its use in patients with suspected bacteremia . METHODS: A MEDLINE search was performed of English-language articles published from 1990 to 2000 on the treatment of CAP . This article reviews the treatment of CAP, with emphasis on the use of clarithromycin . CONCLUSION: Although laboratory surveillance studies have reported macrolide-resistant S . pneumoniae, recent evidence defining the mechanism of this resistance, coupled with the pharmacokinetic properties of the macrolide agents, suggests that the actual rate of clinical macrolide resistance is low.

Joint Bone Spine, 2000, 67(4), 346 - 8
Juvenile relapsing periarteritis nodosa and streptococcal infection; Tonnelier JM et al.; Classic polyarteritis nodosa is a multisystem inflammatory disease associated with necrotizing vasculitis of small and medium arteries . In most cases, the causes of polyarteritis nodosa remain unknown, but viruses (HBV, HCV, HIV) and microbes (especially streptococcus) have been considered as etiologic or contributing factors . A 13-year-old boy was admitted with fever, skin lesions, polyarthritis and muscle involvement . A muscle biopsy demonstrated a necrotizing vasculitis and antistreptolysin titre was tremendously increased . His condition improved following the administration of oral steroids but he experienced relapses 5 and 12 years later when penicillin withdrawal was attempted . The flares were accompanied by a major increase of antistreptolysin titre and response to corticosteroid was obtained . He is currently 38 years old and he remains well on prophylactic penicillin . Polyarteritis nodosa in children may occur after a streptococcal infection . It may be prudent to consider penicillin prophylaxis in patients with periarteritis nodosa when a streptococcal etiology is documented or highly suspected.

Res Microbiol, 2000 Jul-Aug, 151(6), 457 - 63
Is the Ami-AliA/B oligopeptide permease of Streptococcus pneumoniae involved in sensing environmental conditions?
Claverys JP, Grossiord B, Alloing G.
Streptococcus pneumoniae is a fastidious obligate parasite requiring several amino acids for growth . Oligopeptide uptake mediated by the Ami ABC permease is therefore important for nutrition but this could not account for the highly pleiotropic phenotype exhibited by Ami mutants . The hypothesis that peptide transport plays a pivotal role in sensing environmental conditions and indirectly modulates the expression of several genes is discussed.

Res Microbiol, 2000 Jul-Aug, 151(6), 453 - 6
Transformation in Streptococcus pneumoniae: mosaic genes and the regulation of competence; Hakenbeck R; The presence of highly divergent mosaic blocks in penicillin binding protein genes responsible for penicillin resistance in Streptococcus pneumoniae implies that transformation is an important tool for the evolution of this pathogen . Genetic competence depends on production of the competence signaling peptide CSP, the processed product of comC, which is curiously part of a mosaic gene arrangement itself . Expression of comC is part of a complex regulatory network involving at least two receptor kinase/transcriptional regulator pairs: ComD/E, which is responsible for induction, and CiaH/R, which inhibits expression of the comCDE operon.

Res Microbiol, 2000 Jul-Aug, 151(6), 445 - 51
Regulation of competence for genetic transformation in Streptococcus pneumoniae: a link between quorum sensing and DNA processing genes; Morrison DA et al.; Competence for genetic transformation in pneumococcus depends on the coordinated functioning of a dispersed regulon responsible for production of proteins active in DNA binding, uptake, and recombination . This regulon is characterized by a shared noncanonical promoter consensus, TACGAATA, and is capable of 100-fold expression modulations . This review discusses recent evidence that its regulation depends on a novel sigma factor, itself controlled by an autostimulatory quorum sensing system that acts through an extracellular peptide signal.

Res Microbiol, 2000 Jul-Aug, 151(6), 437 - 43
Biological roles of two new murein hydrolases of Streptococcus pneumoniae representing examples of module shuffling; Lopez R et al.; We have found two murein hydrolases (LytB and LytC) tightly bound to the cell envelope that have completely changed the domain building plan previously reported for the murein hydrolases of Streptococcus pneumoniae . The active center of LytB and LytC is located at the C-terminal, whereas the binding domain is at the N-terminal . LytC has been characterized as the first lysozyme of S . pneumoniae and behaves as an autolysin at 30 degrees C . LytB appears as the main hydrolase responsible for cell separation since inactivation of lytB leads to the formation of long chains of more than 100 cells . These findings indicate that genetic adaptation of mobile domains is extremely efficient in pneumococcus.

Res Microbiol, 2000 Jul-Aug, 151(6), 429 - 35
Current trends in capsular polysaccharide biosynthesis of Streptococcus pneumoniae; Garcia E et al.; The capsular gene cluster (cap/cps) of 13 out of the 90 known pneumococcal types has been sequenced . The cap/cps operon, located between dexB and aliA in the Streptococcus pneumoniae chromosome, contains some of the genes responsible for the synthesis of the type-specific polysaccharide flanked by four conserved open reading frames . The biochemical function of only a few capsular genes has been established, whereas the role of the flanking regions is controversial . Remarkably, only one gene (tts) located outside the cap locus is required for the synthesis of type 37 capsule . Moreover, other genes not linked to the cap gene cluster are also needed for capsule synthesis in pneumococcus.

Res Microbiol, 2000 Jul-Aug, 151(6), 413 - 9
Virulence factors and the pathogenesis of disease caused by Streptococcus pneumoniae; Mitchell TJ; Streptococcus pneumoniae is a major pathogen of man causing diseases such as pneumonia, meningitis and otitis media . The mechanisms by which this organism causes these diseases are still largely unknown . The use of molecular approaches to identifying and studying putative virulence factors in combination with the application of animal models has allowed some of the mechanisms of the disease process to be defined.

Res Microbiol, 2000 Jul-Aug, 151(6), 407 - 11
Molecular biology of Streptococcus pneumoniae: an everlasting challenge; Sicard M et al.; Streptococcus pneumoniae is a model for elucidating: 1) recombination steps of DNA, from its discovery to polarity of integration; 2) long-patch mismatch repair, short-patch repair triggered by A/G and exclusion of deletions; 3) resistance to beta-lactam antibiotics; and 4) factors of virulence . Several of these topics remain a challenge for future investigations.

Sante, 2000 Mar-Apr, 10(2), 93 - 6
{Empyema caused by Staphylococcus aureus in children: the experience of the Albert Royer Children's Hospital at Fann University Hospital, Dakar}; Ndiaye O et al.; We report a retrospective study of 58 cases of empyema caused by Staphylococcus aureus at the Albert Royer Children's Hospital at the Fann University Hospital, between January 1st 1992 and December 31st 1995 . Staphylococcus aureus is the principal bacterium responsible for pleural effusions in children (54%), way ahead of Streptococcus pneumoniae (19%) . Most of the children affected (86%) are less than 30 months old . Theses infections are often serious due to the resistance of the bacterium to the usual antibiotics, the lack of solid research data and mechanical complications associated with the effusion . Treatment is based on the use of an appropriate bactericidal antibiotic treatment and pleural drainage.

Int J Antimicrob Agents, 2000 Sep, 16(1), 17 - 24
Susceptibility of 1100 Streptococcus pneumoniae strains isolated in 1997 from seven Latin American and Caribbean countries . Laser Study Group; Jacobs MR et al.; The antimicrobial susceptibility to beta-lactam and non-beta-lactam agents of 1100 isolates of Streptococcus pneumoniae recovered in 1997 from 16 centres in Argentina, Brazil, Chile, Mexico, Panama, Venezuela and West Indies was studied using E-test and disk diffusion methods . A total of 23.6% of isolates had raised penicillin MICs (16.7% intermediate and 6.9% resistant) . The susceptibility of the other agents tested, from most active to least active, were, amoxycillin/clavulanate (99.5% susceptible); chloramphenicol (93.2%); cefotaxime (91.7%); erythromycin (87.1%); tetracycline (74.6%); trimethoprim/sulphamethoxazole (TMP-SMZ) (55.4%); and cefaclor (52.8%) . The highest proportion of strains resistant to penicillin, chloramphenicol, erythromycin, tetracycline and TMP-SMZ was found in strains from Mexico while resistance to these agents was lowest in strains from the West Indies . Prevalence of penicillin resistance (including intermediate and resistant isolates) in each of the countries, from highest to lowest was, Mexico (40.8%); Chile (31.3%); Panama (23.0%); Venezuela (21.9%); Argentina (19.1%); Brazil (12.9%); and West Indies (7.1%) . Based on current levels of antimicrobial resistance of S . pneumoniae in Latin American and Caribbean countries, continued surveillance efforts are necessary in order to guide clinical empiric treatment and provide for judicious use of antimicrobial agents.

Curr Opin Chem Biol, 2000 Aug, 4(4), 433 - 9
New approaches in the treatment of bacterial infections; Bush K et al.; Recently, several new drugs for the treatment of bacterial infections have been developed . Quinupristin/dalfopristin, moxifloxacin and gatifloxacin have been approved throughout the world for clinical use . Levofloxacin has been approved for the treatment of community-acquired pneumonia caused by penicillin-resistant Streptococcus pnuemoniae . The Food and Drug Administration has approved linezolid for clinical use, and new drug applications for gemifloxacin and telithromycin were filed . Other new targets have surfaced in the quest for novel antibacterial agents.

Drug Chem Toxicol, 2000 Aug, 23(3), 433 - 57
Glycidol modulation of the immune responses in female B6C3F1 mice; Guo TL et al.; The immunotoxic potential of glycidol was evaluated in female B6C3F1 mice using a battery of functional assays and three host resistance models . Glycidol was administered to the animals by oral gavage as a solution in sterile distilled water daily for 14 days at doses of 25, 125 and 250 mg/kg . In tier I, we observed that glycidol exposure produced a dose-related decrease in splenocyte IgM antibody-forming cell response to sheep red blood cells (sRBC); the spleen natural killer (NK) cell activity was also decreased . A decrease in B cell proliferative responses to anti-IgM F(ab')2 and/or interleukin-4 (IL-4) was observed while the splenocyte proliferative responses to T cell mitogen ConA and B cell mitogen LPS were not affected . The splenocyte proliferative response to allogeneic cells as evaluated in the mixed leukocyte reaction (MLR) to DBA/2 spleen cells was not affected . In tier II, we found that exposure to glycidol decreased the number and percentage of B cells and the absolute number of CD4+ T cells in the spleen while the number of total T cells, CD8+ T cells and CD4+CD8+ T cells was not affected . The cytotoxic T lymphocyte (CTL) response to mitomycin C-treated P815 mastocytoma was not affected; the cytotoxic activity of peritoneal macrophages was not suppressed . Moreover, the host resistance to Listeria monocytogenes was not affected although a slight increase in host resistance to Streptococcus pneumoniae was observed . However, exposure to glycidol decreased host resistance to the B16F10 melanoma tumor model with the maximal tumor formation in lung observed in the high dose group . Overall, these dada support the finding that glycidol is an immunosuppressive agent in female B6C3F1 mice.

Adv Exp Med Biol, 2000, 480, 307 - 11
Vaccines against bovine mastitis due to Streptococcus uberis current status and future prospects; Leigh JA; The prevalence of bovine mastitis in the UK has been reduced over the past twenty five years due to the implementation of a five-point control plan aimed at reducing exposure, duration and transmission of intramammary infections by bacteria . This has markedly reduced the incidence of bovine mastitis caused by bacteria which show a contagious route of transmission but has had little effect on the incidence of mastitis due to bacteria which infect the gland from an environmental reservoir . Streptococcus uberis is one such bacterium which is responsible for a significant proportion of clinical mastitis worldwide . The inadequacies of the current methods of mastitis control have led to the search for additional measures to prevent intramammary infection by this bacterium . A live vaccine in combination with an intramammary administration of a soluble cell surface extract was shown to induce protection of the mammary gland from experimental challenge with S . uberis . Protection was strain specific, but was achieved in the absence of opsonic activity and without a large influx of neutrophils . One hypothesis is that protection was achieved by reducing the rate of bacterial growth in vivo . This view has led to the identification and exploitation of a novel plasminogen activator as a vaccine antigen . Vaccines containing this antigen conferred cross strain protection.

J Vasc Surg, 2000 Sep, 32(3), 602 - 6
Dacron carotid patch infection: a report of eight cases; Rizzo A et al.; From 1995 through 1998, we encountered eight patients with infected Dacron patches after previous carotid endarterectomy . Two of the original operations had been done elsewhere, but the six patients who were collected from our own series represented 0.5% of the 1258 carotid endarterectomies we performed and 1.8% of the 340 synthetic carotid patches we applied without any comparable infections among another 918 patients who received either vein patch angioplasty (n = 843) or primary arteriotomy closure (n = 74) during the same 4-year study period . With a single exception ("no growth"), bacterial cultures that were obtained at the time of the eight reoperations revealed Staphylococcus (n = 4) or Streptococcus (n = 3) species . All of the infected Dacron patches were removed and were replaced with saphenous vein patches (n = 5) or interposition grafts (n = 3), after which appropriate oral (n = 2) or intravenous (n = 6) antibiotics were administered for 2 to 6 weeks . No postoperative deaths occurred, but there were 2 temporary cranial nerve injuries, 1 myocardial infarction, and 1 stroke that was related to preoperative angiography . A recurrent carotid infection has not developed in any of the eight patients during a mean follow-up interval of 16 months (range, 3-36 months).

Biochemistry, 2000 Aug 22, 39(33), 10140 - 6
Synergistic inhibitor binding to Streptococcus pneumoniae 5-enolpyruvylshikimate-3-phosphate synthase with both monovalent cations and substrate; Du W et al.; The inhibitor binding synergy mechanism of the bi-substrate enzyme Streptococcus pneumoniae 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) has been investigated with a linkage thermodynamics strategy, involving direct binding experiments of one ligand conducted over a range of concentration of the other . The results demonstrate that binding of the inhibitor glyphosate (GLP) is highly synergistic with both a natural substrate shikimate-3-phosphate (S3P) and activating monovalent cations . The synergy between GLP and S3P binding was determined to be 1600-fold and is in qualitative agreement with previous work on Escherichia coli EPSPS . The binding molar ratios of S3P and GLP were measured as 1.0 and 0.7 per EPSPS, respectively . Monovalent cations that have been shown previously to stimulate S . pneumoniae EPSPS catalytic activity and its inhibition by GLP were found here to exhibit a similar rank-order with respect to their measured GLP binding synergies (ranging from 0 to > or =3000-fold increase in GLP affinity) . The cation specificity and the sub-millimolar concentrations where these effects occur strongly suggest the presence of a specific cation binding site . Analytical ultracentrifugation data ruled out GLP-binding synergy mechanisms that derive from, or are influenced by, changes in oligomerization of S . pneumoniae EPSPS . Rather, the data are most consistent with an allosteric mechanism involving changes in tertiary structure . The results provide a quantitative framework for understanding the inhibitor binding synergies in S . pneumoniae EPSPS and implicate the presence of a specific cation binding regulatory site . The findings will help to guide rational design of novel antibiotics targeting bacterial EPSPS enzymes.

Allergy, 2000 Aug, 55(8), 732 - 9
Prenatal immune priming with helminth infections: parasite-specific cellular reactivity and Th1 and Th2 cytokine responses in neonates; Pit DS et al.; The present investigation aimed to determine to what extent maternal helminth infection primes parasite-specific cellular responsiveness in neonates . Umbilical cord mononuclear blood cells (UCBC) and peripheral blood mononuclear cells (PBMC) from mothers proliferated in response to mitogenic stimulation with concanavalin A, as well as to bacterial Streptococcus pyogenes-derived (streptolysin O) and helminth-specific antigens of Necator americanus and Onchocerca volvulus . Cellular responses to Echinococcus multilocularis (Em) and Oesophagostomum bifurcum (Oes), helminth parasites not endemic in the study area, were absent (for Em) or very low (for Oes due to antigenic cross-reactivity) . Cellular responsiveness to mitogen and antigens was higher in mothers than in their neonates . Several Th1-type (IL-2, IL-12, and IFN-gamma) and Th2-type (IL-5 and IL-10) cytokines were produced by UCBC from neonates and PBMC from mothers . Low levels of IFN-gamma were elicited by UCBC in response to helminth and bacterial antigens, while secretion of IL-2 was pronounced and similarly high in neonates and their mothers . Amounts of IL-5 produced by UCBC in response to bacterial SL-O and mitogenic stimulation (PHA) were low, but equivalent levels of IL-5 were induced by intestinal helminth and filaria-derived antigens in neonates and mothers . A pronounced production of IL-10 and IL-12 by UCBC was observed--spontaneous IL-10 and IL-12 secretion by UCBC was higher in neonates than by PBMC from mothers . Net amounts of IL-10 elicited by helminth antigens were similar, while net IL-12 in response to mitogen, and bacterial and helminth antigens was significantly higher in mothers than their offspring . Our results indicate that human maternal helminth infection does sensitize in utero for parasite-specific cellular responsiveness in offspring, and also activates specific production of several cytokines, and such children do not present a dominant expression of immunity of either Th1 or Th2.

Australas J Dermatol, 2000 Aug, 41(3), 139 - 43; quiz 144-5
Skin infections and infestations in Aboriginal communities in northern Australia; Currie BJ et al.; The most important skin infections in Aboriginal communities in central and northern Australia are scabies and streptococcal pyoderma . Scabies is endemic in many remote Aboriginal communities, with prevalences in children up to 50% . The cycles of scabies transmission underlie much of the pyoderma . Up to 70% of children have skin sores, with group A streptococcus (GAS) the major pathogen . Group A streptococcus is responsible for the continuing outbreaks of post-streptococcal glomerulonephritis and acute rheumatic fever (ARF) . The cycles of scabies transmission in dogs and humans do not appear to significantly overlap . Guidelines have been developed for community control of scabies and skin sores and successful community initiated coordinated programmes have occurred . The anthropophilic dermatophyte Trichophyton rubrum is ubiquitous in many communities, again reflecting living conditions . Other skin infections related to the tropical environment include melioidosis, nocardiosis, Chromobacterium violaceum and chromoblastomycosis . Sustainable and long-term improvements in scabies, skin sores and GAS-related disease and tinea require fundamental changes that address social and economic inequities and, in particular, living conditions and overcrowding.

Int J Clin Pract, 2000 Jun, 54(5), 329 - 32
Moxifloxacin (Avelox): an 8-methoxyquinolone antibacterial with enhanced potency; Ball P; Moxifloxacin is a novel 8-methoxyquinolone with enhanced potency against important Gram-positive pathogens, notably Streptococcus pneumoniae . It retains class activity against Gram-negative bacteria . Currently available for oral use, it has a prolonged half-life, enabling once-daily administration and reflecting balanced renal and hepatic elimination . Clinical trials have demonstrated an excellent safety record with minor class effects in the skin and gastrointestinal systems . Potential for phototoxicity is minimal and moxifloxacin is free of clinically significant neurological, hepatic or cardiac effects . Investigated primarily in respiratory infections, moxifloxacin has shown excellent performance in community-acquired pneumonia (both pneumococcal and atypical), acute exacerbations of chronic bronchitis and acute maxillary sinusitis . It is available in many European countries and in the US where it is rapidly establishing clinical acceptance and formulary inclusion.

Rhinology, 2000 Jun, 38(2), 68 - 71
Bactrim reduces the inflammatory response in a murine model of acute rhinosinusitis; Won YS et al.; OBJECTIVE: To determine whether treatment with an antibiotic (trimethoprim-sulfamethoxazole) reduced the inflammatory response in a murine form of Streptococcus pneumoniae-induced rhinosinusitis . DESIGN: We randomized 18 C57BL/6 mice to either treatment with intraperitoneal trimethoprim-sulfamethoxazole (Bactrim, 30 mg/kg) or no treatment (control) . After 2 days, we inoculated all C57BL/6 mice intranasally with a Bactrim-susceptible strain of Streptococcus pneumoniae, ATCC 49619, suspended in Trypticase soy broth . At day 5 after bacterial inoculation, we sacrificed the mice and prepared histopathologic sections of their sinuses after culturing their nasal cavities by lavage . SETTING: Animal care facility at a tertiary, academic institution . METHODS: The histopathologic sections of the sinuses were examined in a blind manner for the percent of sinus cavity area occupied by neutrophil clusters, and for the number of neutrophils per square millimeter of sinus mucosa . RESULTS: The Bactrim group had a significantly smaller sinus area occupied by neutrophil clusters (1.58% +/- 1.13 vs 4.38% +/- 3.41; P < 0.05), significantly fewer neutrophils infiltrating the mucosa (58.81 +/- 29.63/mm2 vs 105.85 +/- 48.49/mm2; P < 0.05), and significantly less growth of Streptococcus pneumoniae colonies in the intranasal cultures (8 few and 1 moderate vs 3 few, 3 moderate, and 1 many; P = 0.05) compared to the control group . CONCLUSION: In our murine model of acute rhinosinusitis, Bactrim decreased the number of neutrophil clusters in the sinus cavities, the number of neutrophils infiltrating the sinus mucosa, and the growth of Streptococcus pneumoniae . We propose that our murine model can be used for the study of the pathophysiology and treatment of acute rhinosinusitis.

Arch Dis Child, 2000 Sep, 83(3), 231 - 3
Outcome of invasive pneumococcal disease: a UK based study . Oxford Pneumococcal Surveillance Group; Shackley F et al.; METHODS: The records of 106 children aged less than 5 years with invasive disease caused by Streptococcus pneumoniae were reviewed . RESULTS: The clinical manifestations were meningitis (37%), upper respiratory tract infection (24%), pneumonia (19%), and occult bacteraemia (18%) . One child died and seven had persisting neurological impairment . Five serotypes caused 83% of disease and 92% of the serotypes are included in the seven valent conjugate vaccines which are undergoing trials . CONCLUSIONS: These data suggest that S pneumoniae infection is associated with a low case fatality rate but substantial morbidity in the UK.

Antimicrob Agents Chemother, 2000 Sep, 44(9), 2585 - 7
Characterization of a genetic element carrying the macrolide efflux gene mef(A) in Streptococcus pneumoniae; Santagati M et al.; The mef(A) gene from a clinical isolate of Streptococcus pneumoniae exhibiting the M-type resistance to macrolides was found to be part of the 7,244-bp chromosomal element Tn1207.1, which contained 8 open reading frames . orf2 encodes a resolvase/invertase, and orf5 is a homolog of the macrolide-streptogramin B resistance gene msr(SA).

Antimicrob Agents Chemother, 2000 Sep, 44(9), 2578 - 80
Inhibitory effects of plant polyphenoloxidase on colonization factors of Streptococcus sobrinus 6715; Cowan MM et al.; Exogenously added polyphenoloxidase (EC 1.14.18.1), an enzyme which oxidizes tyrosine residues and is commonly found in many dietary components, abolished the aggregation of Streptococcus sobrinus 6715 by high-molecular-weight dextran . The enzyme decreased glucan-binding lectin and/or glucosyltransferase I activities.

Antimicrob Agents Chemother, 2000 Sep, 44(9), 2564 - 6
Successful trovafloxacin prophylaxis against experimental streptococcal aortic valve endocarditis; Katsarolis I et al.; Single-dose trovafloxacin (15 mg/kg given intravenously {i.v.}) and ampicillin (40 mg/kg given i.v.) protected 38 and 33% of animals challenged with an ampicillin-tolerant strain of Streptococcus oralis, respectively . As a double-dose regimen, trovafloxacin afforded total protection (100%; P < 0.001 versus controls) . Trovafloxacin is the first fluoroquinolone effective in preventing experimental streptococcal endocarditis.

Antimicrob Agents Chemother, 2000 Sep, 44(9), 2521 - 4
Analysis of ciprofloxacin activity against Streptococcus pneumoniae after 10 years of use in the United States; Sahm DF et al.; As the most commonly used fluoroquinolone in the United States since 1987, ciprofloxacin has exerted the greatest selective pressure on S . pneumoniae and provides a valuable marker to evaluate the actual and potential emergence of fluoroquinolone resistance in this species . Analysis of susceptibility results obtained with 5,640 strains collected from throughout the United States showed that only 16 (0.3%) of the isolates demonstrated MICs of > or =4 microg/ml . The prevalence of this phenotype was significantly higher (P < 0.05) among penicillin-resistant populations, among isolates from patients >64 years old, and among respiratory isolates . However, >99% of strains had MICs of <4 microg/ml regardless of the risk group examined, and the MIC population distributions were the same for each risk group . These findings demonstrate that the phenotype of a MIC of > or =4 microg/ml remains uncommon after 10 years of ciprofloxacin use; however, these findings are no reason to become complacent with regard to appropriate use of fluoroquinolones and the need to carefully track resistance trends . Equally important is careful analysis of data that result from surveillance in terms of risk factors and other associated trends so that resistance and susceptibility, and their consequences, are neither over- nor underestimated.

Arq Bras Cardiol, 2000 Mar, 74(3), 217 - 31
A study of infectious endocarditis in Ribeirão Preto, SP-Brazil . Analysis of cases occurring between 1992 and 1997; Ruiz Junior E et al.; OBJECTIVE: To analyze the epidemiology, diagnosis, clinical aspects causes and evolution of infectious endocarditis . METHODS: The patients analyzed were treated at the University Hospital of the Faculdade de Medicina of Ribeirao Preto-USP and had a diagnosis of infectious endocarditis defined by Duke's criteria, which classifies infectious endocarditis as native, prosthetic valve or that occurring in intravenous drug users . RESULTS: One hundred and eighty episodes of infectious endocarditis in 168 patients were observed . Echocardiograms in 132 (73.3%) provided a diagnosis of infectious endocarditis in 111 (84%) patients; mitral valves were affected in 55 (30.5%), tricuspid valves in 30 (16.6%) and the aortic valve in 28 (15.5%) patients . Hemocultures were performed in 148 (93.8%) episodes of IE . The most commonly isolated infectious organisms were Staphylococcus aureus in 46 (27.2%) patients and Streptococcus viridans in 27 (15.9%) . Complications occurred in 116 (64.4%) patients and 73 (40.5%) of the patients died . CONCLUSION: The general profile of the observed infectious endocarditis was similar to that reported in studies performed in other countries and included users of intravenous drugs . The high degree of mortality observed is not compatible with progress in diagnosis and treatment of infectious endocarditis and is probably due to the absence of diagnostic suspicion . The high frequency of fatal cases of septicemia (45.1% of deaths) in the patients studied indicates that unnoticed cases of infectious endocarditis had only been diagnosed at necropsy.

Eur J Biochem, 2000 Sep, 267(17), 5520 - 30
Unique poly(glycerophosphate) lipoteichoic acid and the glycolipids of a Streptococcus sp . closely related to Streptococcus pneumoniae; Roethlisberger P et al.; The Streptococcus sp . studied here is closely related to Streptococcus pneumoniae with 98.6% 16S rRNA similarity and 65% DNA/DNA homology . We isolated the lipoteichoic acid and the membrane glycolipids whose structures were established using conventional procedures and NMR spectroscopy . The lipoteichoic acid contains a linear 1,3-linked poly(glycerophosphate) chain which is partly substituted with D-alanine ester and is phosphodiester-linked to O6 of beta-D-Galf(1-->3)acyl2Gro . This lipoteichoic acid is the first example in which a monohexosylglycerol serves as the glycolipid anchor; and with an average chain length of 10 glycerophosphate residues it is the shortest known to date . MS analysis, applied for the first time to a native acylated lipoteichoic acid, revealed a continuous increase in chain length from seven to 17 glycerophosphate residues with a maximum at 10, and allowed identification of the fatty acid combinations . Membrane glycolipids consisted of beta-D-Galf(1-->3)acyl2Gro (9%), alpha-D-Glcp(1-->3)acyl2Gro (22%), alpha-D-Galp(1-->2)-alpha-D-Glcp(1-->3)acyl2Gro (64%) and alpha-D-Galp(1-->2)-(6-O-acyl)-alpha-D-Glcp(1-->3)acyl2Gro (5%) . It is noteworthy that in lipoteichoic acid biosynthesis, Galfacyl2Gro, a less abundant membrane glycolipid, is selected as the lipid anchor . Despite the genetic relatedness to Streptococcus pneumoniae, the lipoteichoic acid structure is quite different to the complex structure of pneumococcal lipoteichoic acid {T . Behr et al . (1992) Eur . J . Biochem . 207, 1063-1075}, thus providing an example that minor differences in DNA sequence exert major changes in macromolecular structure.

J Infect Dis, 2000 Sep, 182(3), 833 - 9 Epub 2000 Aug 17.
Molecular epidemiology of Streptococcus pneumoniae causing invasive disease in 5 countries; Henriques B et al.; A multicenter study was done during 1993-1995 to investigate prospectively the influence of several prognostic factors for predicting the risk of death among patients with pneumococcal bacteremia . Five centers located in Canada, the United Kingdom, Spain, Sweden, and the United States participated . Clinical parameters were correlated to antibiotic susceptibility and serotyping of the 354 invasive pneumococcal isolates collected and to molecular typing of 173 isolates belonging to the 5 most common serotypes (14, 9V, 23F, 3, and 7F) . Serotype 14 was the most common among all isolates, but serotype 3 dominated in fatal cases and in isolates from Spain and the United States, the countries with the highest case-fatality rates . Fewer different patterns were found among the type 3 isolates, which suggests a closer clonal relationship than that among isolates belonging to other serotypes . Of type 3 isolates from fatal cases, 1 clone predominated . Other penicillin-susceptible invasive clones were also shown to spread in and between countries.

J Chemother, 2000 Aug, 12(4), 299 - 305
Assessment of the susceptibility of Streptococcus pneumoniae to cefaclor and loracarbef in 13 countries; Bandak SI et al.; Between July 1998 and July 1999, 2,644 clinical isolates of Streptococcus pneumoniae were collected from 27 study centers in 13 countries and their susceptibilities to penicillin, cefaclor and loracarbef were determined by E-test" (AB BIODISK, Solna, Sweden) . Overall, 96.3% of isolates were penicillin-susceptible (79.8%) or -intermediate (16.6%) (MIC, < or = 1 microg/ml) . Rates of penicillin-resistant S . pneumoniae isolation varied widely and were highest in the study centers tested in New Zealand (10.9%), Canada (10.0%), Mexico (9.1%) and the United States (5.1%) . Low rates of penicillin-resistance were found in the study centers tested in Russia (0%), Turkey (0%), Brazil (0.5%), Germany (0.6%), Philippines (1.6%), Italy (2.1%), United Kingdom (2.3%), Australia (3.0%) and Poland (3.1%) . Using recently published NCCLS interpretative breakpoints (M100-S10, 2000), 87.2% (median) of all isolates tested were cefaclor-susceptible and 87.8% (median) of all isolates tested were loracarbef-susceptible . Of the penicillin-susceptible S . pneumoniae isolates, 99.5% were susceptible to both cefaclor and loracarbef . Susceptibility to cefaclor and loracarbef was also retained by 30.8% and 32.9% of penicillin-intermediate isolates, respectively . These findings are in contrast to recent publications reporting lower cefaclor and loracarbef activities using non-validated interpretative criteria . In conclusion, rates of penicillin resistance among recent clinical isolates of pneumococci remain low in many centers worldwide . Cefaclor and loracarbef demonstrated excellent in vitro activity against recent clinical isolates of penicillin-susceptible and many isolates of penicillin-intermediate S . pneumoniae.

Pathol Biol (Paris), 2000 Jun, 48(5), 463 - 6
Comparison of the in vitro activity of pristinamycin and quinupristin/dalfopristin against Streptococcus pneumoniae; Lozniewski A et al.; The in vitro activity of quinupristin/dalfopristin, a new injectable streptogramin, and pristinamycin was evaluated against 200 recently isolated clinical Streptococcus pneumoniae strains expressing various degrees of susceptibility to penicillin G and erythromycin . MICs were determined by the agar dilution method . All strains were susceptible to pristinamycin irrespective of their susceptibility to penicillin G or erythromycin (MIC90: 0.25 mg/L for each phenotype) . The activity of quinupristin/dalfopristin was slightly lower than that of pristinamycin against 42 penicillin G-susceptible/erythromycin-susceptible strains (MIC90: 0.5 mg/L), 13 penicillin G-susceptible/erythromycin-resistant strains (MIC90: 1 mg/L), 25 penicillin G-intermediate or -resistant/erythromycin-susceptible strains (MIC90: 0.5 mg/L) and 120 penicillin G-intermediate or -resistant/erythromycin-resistant strains (MIC90: 0.5 mg/L) . The activity of both streptogramins was not significantly altered in case of erythromycin resistance . Thus, both streptogramins might be useful for the treatment of penumococcal infections, especially in cases of multiresistant strains.

Akush Ginekol (Sofiia), 2000, 39(2), 34 - 5
{The treatment of bacterial vaginosis with Dalacin V cream}; POrozhanova V et al.; To asses the efficiency of the 2% clindamycin phosphate creme given in 3 and 7 daily courses officially designer for the treatment of bacterial vaginosis (BV) . METHODS: The study includes 65 patients who have microbiological data for BV 11 of the women are pregnant (18.46%) . The microbiological study includes there agent: Streptococcus agalactiae, E . colli, Gardnerella vaginalis, Peptostreptococcus species, Prevotella species, Mobiluncus species, Staphylococcus epidermidis et Enterococcus fecalis . The controls visit was assessed on the 7'} and 28'} day after the therapy . RESULTS: There were successful results on the 84.3% of the patients after 7 day course but in the 3-day course the good results were showed in 73.91% of the women . After the 28"} day there were only few successful results 43% . CONCLUSIONS: The clindamycin phosphate is more preferable method for the treatment of BV.

Infect Immun, 2000 Sep, 68(9), 5425 - 9
Possible release of an ArgGlyArgProGln pentapeptide with innate immunity properties from acidic proline-rich proteins by proteolytic activity in commensal streptococcus and actinomyces species; Li T et al.; This study suggests degradation of salivary acidic proline-rich proteins (PRPs) into potential innate-immunity-like peptides by oral Streptococcus and Actinomyces species . PRP degradation paralleled cleavage of Pro-containing substrates . PRP degradation by S . gordonii strain SK12 instantly released a Pyr(1)-Pro(104)Pro(105) and a Gly(111)-Pro(149)Gln(150) peptide together with a presumed Arg(106)Gly(107)Arg(108)Pro(109)Gln(110) pentapeptide . The synthetic Arg(106)Gly(107)Arg(108)Pro(109)Gln(110) peptide desorbed bound bacteria and counteracted sucrose-induced decrease of dental plaque pH in vitro.

Braz J Infect Dis, 2000 Feb, 4(1), 1 - 8
Perspectives on the development of new antimicrobial agents for resistant gram-positive pathogens; Jones RN; There is great public and professional concern related to antimicrobial resistance, especially among Gram-positive pathogens associated with high morbidity and mortality . Penicillin-nonsusceptible Streptococcus pneumoniae, glycopeptide resistant enterococci, and oxacillin-resistant (MRSA) or vancomycin-intermediate (VISA) Staphylococcus aureus isolates continue to escalate in occurrence leading to the widespread use of empiric combination regimens . Newer, often novel, agents seem necessary to combat these pathogens . Among these, quinupristin/dalfopristin (Synercid), evernimicin or SCH 27899 (Ziracin), and linezolid (Zyvax) have the highest potency, widest spectrum, and most clinical experience . Among the quinolones (gatifloxacin, gemifloxacin, moxifloxacin), gatifloxacin is closest to clinical use and appears safe based on initial trial reports . Several broad-spectrum beta-lactams ("fourth-generation" cephalosporins, carbapenems) are expected to be used with increasing frequency as a result of the emerging high rates of specific beta-lactamases that compromise the use of ceftriaxone, ceftazidime, and many beta-lactamase inhibition/ penicillin combinations . Among these agents, cefepime and meropenem are the most potent and broadest in clinical application in their respective classes . Physicians must stay informed about drug development and antimicrobial resistance by using results from local surveillance programs . When these data are unavailable, physicians should consider the use of national or global monitoring systems (SENTRY) to direct empiric antimicrobial selection.

New Microbiol, 2000 Jan, 23(1), 37 - 45
Synergic activities of streptococcal pyrogenic exotoxin A and lipoteichoic acid in cytokine induction; Cusumano V et al.; The present study was carried out to gain insight into the mechanisms involved in the pathogenesis of streptococcal toxic shock syndrome (TSS) and other acute invasive diseases caused by Streptococcus pyogenes (GAS) . Specifically, since both whole bacteria and their soluble products are often present in the blood in these conditions, we sought to detect possible synergic activities of somatic and extracellular products in inducing mediators release . For this purpose, whole blood cultures from healthy donors were incubated with different concentrations of streptococcal pyrogenic exotoxin A (SpeA), which is considered a major molecular effector of TSS, heat-killed GAS and cell-wall components such as lipoteichoic acid (LTA) and soluble peptidoglican (sPGN) . Significant levels of TNF-alpha, IL-1 alpha and IFN-gamma were found in supernatants from cultures incubated with each of the four inducers alone . Whole GAS and both cell-wall components were more effective (p < 0.05) than SpeA in inducing cytokine release . Whole GAS, at weight basis, was a more potent inducer than LTA and sPGN and LTA, at weight basis, was a more potent inducer than sPGN . In order to verify possible additive or synergic effects of exotoxic and parietal compounds in inducing cytokine release, whole blood cells were incubated with mixtures of SpeA and LTA at different molecular ratio . TNF-alpha, IL-1 alpha and IFN-gamma levels in supernatants were significantly (p < 0.05) higher in supernatants of cultures stimulated simultaneously with the two components than those of cultures stimulated with a single agent . Moreover, these levels were significantly higher than the sum of cytokine levels induced by single components . This study shows that parietal compounds can act in synergy with exotoxins in inducing the release of cytokines, which appear to be the major mediators of TSS.

DNA Cell Biol, 2000 Jul, 19(7), 401 - 8
High-level expression of a truncated wall-associated protein A from the dental cariogenic Streptococcus mutans; Yoder S et al.; Streptococcus mutans plays a primary role in the formation of dental caries . Previously, in our laboratory, an S . mutans genomic library was prepared, and the wapA gene was cloned into the shuttle vector, pSA4/4B2 . To generate overexpression of wapA and to facilitate efficient purification of the WapA protein for use as an immunogen, an expression vector with the strong tac promoter was used . In order to answer questions regarding the optimization of solubility and expression based on gene size or the hydrophobicity of the protein product, 12 truncated constructs of the wapA gene were prepared using PCR . The truncated products were subcloned into the pGEX-6P-1 glutathione S-transferase (GST) fusion vector and expressed in E . coli BL21 . The fusion proteins were analyzed by SDS-PAGE and confirmed by analysis with anti-GST and anti-WapA antibodies . Our study suggests that abrogation of the wapA promoter is necessary for expression of this gene in this expression system . Deletion of the signal peptide and the hydrophobic C terminus of WapA increased expression compared with the full-length construct, and truncation at the protease cleavage site of the C-terminal region greatly increased the stability of the protein without a loss in reactivity with the anti-WapA antibody . Western immunoblot analysis with anti-WapA antiserum clearly showed that the majority of the epitopes of the GST-WapA fusions are located in the N-terminal region of WapA . The immunogenicity of the various WapA fusion products is being examined in mice and rats to further map the immunologically dominant regions of the protein . This method effectively increased the expression of WapA and should contribute to the further understanding of gene expression of E . coli, as well as aid in the characterization of this protein for future immunologic evaluation.

Int Dent J, 2000 Apr, 50(2), 79 - 85
In vitro colonisation of acrylic resin denture base materials by Streptococcus oralis and Actinomyces viscosus; Kagermeier-Callaway AS et al.; AIM: The aim of the study was to compare the attachment of two typical strains of oral bacteria to four denture base materials . DESIGN: In vitro study . METHOD: Discs of acrylic resin denture base materials (Paladon 65, polished and unpolished; Palapress; Microbase, polished and unpolished, and Triad VLC) were placed into Petri dishes with Schaedler's medium, inoculated with Streptococcus oralis 34 or Actinomyces viscosus T14V . MAIN OUTCOME MEASURES: After 24 h or 48 h the numbers of adhering bacteria were measured . RESULTS: The bacteria adhered to all discs in similar numbers: 3-9 x 10(6)/ml (viable cell count) and 9-22 x 10(8)/ml (total cell count) for T14V, and 2-6 x 10(6)/ml (viable cell count) and 1.5-3 x 10(8)/ml (total cell count) for 34 . CONCLUSIONS: Polishing had little effect on adherence . Denture base materials are not resistant against adherence and possible surface damage by oral bacteria . Therefore, thorough oral hygiene is important for denture wearers.

East Afr Med J, 2000 Jan, 77(1), 34 - 6
Hippurate hydrolysis and Christie, Atkins, Munch-Peterson tests as epidemiological diagnostic tools for Streptococcus agalactiae carriage in pregnancy; Nsagha DS et al.; OBJECTIVE: To evaluate the Christie, Atkins, Munch-Peterson (CAMP) and hippurate hydrolysis reactions as diagnostic tools for Streptococcus agalactiae carriage in pregnancy . DESIGN: Observational, analytical case-control study . SETTING: Hospital-based study in a primary and a tertiary health care institution . PATIENTS: One hundred and six pregnant and 56 non-pregnant (controls) women were included in the study . The participants were of different socio-economic status . A volunteer sample was used . About 800 subjects were contacted and 162 participated in the study . RESULTS: The sensitivity of the screening test varied from 25% for the CAMP test to 77.78% for the hippurate hydrolysis reaction . The specificity was the same for both tests at (50%) . A significant difference in positivity between the CAMP and hippurate hydrolysis reactions (95% confidence limit, P < 0.05) was observed . The predictive values of the positive test were 66.6% (CAMP) and 87.55% (hippurate hydrolysis) while the negative test were 14.29% (CAMP) and 33.30% (hippurate hydrolysis) . Pregnant women had 0.33 chances of being GBS carriers with the CAMP compared to 3.5 with the hippurate hydrolysis . CONCLUSION: The hippurate hydrolysis test is highly recommended since the reagents are easily available and the organism was easily isolated using this method . The presence of GBS in the anorectum and endocervix is likely to induce systemic and local immunity in the female genital tract . This can contribute to the development of a mucosal vaccine for GBS diseases.

Wien Klin Wochenschr, 2000 Jul 7, 112(13), 566 - 75
Pneumonia in the elderly--what makes the difference?
Schafer H, Ewig S.
Pneumonia has a particularly high incidence in the elderly, the cardinal risk factors being comorbidity and malnutrition . The independent bearing of age on the aetiology of pneumonia is a matter of controversy and is probably limited . Streptococcus pneumoniae is uniformly the most frequent pathogen . Elderly patients with pneumonia are frequently oligosymptomatic . Quite often, mental confusion may be the only clinical symptom . Physical and chest radiograph examination have specific and important pitfalls . Mental confusion as a surrogate marker of severe sepsis should be added to the criteria for assessing the severity of disease . Pneumonia in the elderly is associated with a considerably increased mortality, but age does not appear to be an independent predictor of death . The disease continues to be the old man's friend: survivors of a pneumonia episode are more likely to die during follow-up as compared to controls . Antimicrobial treatment in the elderly should follow a risk-adopted approach . When selecting antimicrobial agents for the treatment of the elderly, peculiarities in pharmacokinetics, drug interactions and side effects should be considered . The rate of radiographic clearance is inversely correlated with age . All elderly individuals are candidates for vaccination against pneumococci and influenza, particularly in the presence of cardiopulmonary comorbidity and any degree of immunosuppression.

Ann Vasc Surg, 2000 Jul, 14(4), 401 - 4
Infrarenal aortic rupture in association with a contiguous polymicrobial intraabdominal abscess including Eikenella corrodens; Murrell Z et al.; Aortic rupture in association with a contiguous intraabdominal abscess is rare . We report an unusual case of aortic rupture in association with a polymicrobial abscess and review the related literature . Cultures grew Eikenella corrodens, a rare intraabdominal pathogen, as well as betahemolytic streptococcus and S . viridans . The patient was successfully managed by aortic ligation followed by an extraanatomic bypass.

Scand J Clin Lab Invest, 2000 Jul, 60(4), 311 - 21
Peptidoglycan and lipoteichoic acid, components of the streptococcal cell wall, have marked and differential effects on adhesion molecule expression and the production of reactive oxygen species in human whole blood leukocytes; Saetre T et al.; To elucidate the pathophysiology of infections with Streptococcus pyogenes we applied flow cytometric techniques to study dose-response and time-related effects of the streptococcal cell-wall-derived components lipoteichoic acid (LTA 0.005 to 50 microg/ml) and peptidoglycan (10 and 100 microg/ml) on the expression of leukocyte adhesion molecules, the CD14 receptor, and the production of leukocyte reactive oxygen species (ROS) . LTA (50 microg/ml, 1-2 h) markedly increased the expression of CD11b (approximately 5-fold), CD11c (approximately 2-fold) and CD11a . Concomitantly, CD62L was downregulated (60%) . Peptidoglycan alone or in combination with LTA had little effect on adhesion molecules, except for an amplification of the downregulation of CD62L to 90% . Monocyte CD14 expression was doubled by LTA . Leukocyte ROS production was 10-fold and 5-fold increased by peptidoglycan in granulocytes and monocytes, respectively . LTA alone had no effect, while the combination of peptidoglycan with LTA doubled the increase in ROS caused by peptidoglycan . Conclusion: LTA and peptidoglycan had marked and differential effects: LTA caused mainly adhesion molecule modulation, whereas peptidoglycan mainly increased ROS production . These changes are important in inflammatory cell activation and recruitment, intracellular microbial killing and adverse tissue injury.

J Infect, 2000 Jul, 41(1), 84 - 90
Vertebral osteomyelitis caused by Streptococcus agalactiae; Solis-Garcia del Pozo J et al.; Streptococcus agalactiae is a rare cause of vertebral osteomyelitis . We present four cases of spondylitis caused by this micro-organism and a review of 20 cases previously described in the literature . Only seven patients (29%) were under 50 years of age . Diabetes mellitus and neoplasms were the most frequent underlying conditions, although 37.5% of the patients did not have any predisposition . Neck or back pain was the most common symptom . Diagnosis depended mainly on magnetic resonance imaging . Blood cultures were positive in 50% of the patients . The duration of antibiotic therapy was 6 weeks for most patients . The outcome was favourable, with none of the patients suffering serious sequelae .

Arch Pediatr, 2000 Jun, 7 Suppl 3, 565s - 571s
{Bacterial meningitis in infants 1 to 8 weeks old}; Zanelli S et al.; Bacterial meningitis in the newborn and infant remains a serious problem, with a mortality rate of 24% and a morbidity rate ranging from 30 to 50% . This retrospective study conducted between January 1982 and December 1997, aims to characterize the epidemiology of bacterial meningitis in infants less than 60 days of age . Thirty-five infants between 6 and 60 days of age, hospitalized for bacterial meningitis in the pediatric units of Edouard-Herriot Hospital in Lyon, France, were included . The clinical presentation was not specific for most cases, hyperthermia being the most common symptom (97%) . Neurological symptoms such as bulging fontanelle or nuchal rigidity were present in 30% and 8% of the cases, respectively . The four predominant meningeal pathogens were: group B streptococcus (36%), Escherichia coli (28%), meningogoccus (8.6%) and Staphylococcus aureus (8.6%) . This study emphasizes the importance of prompt diagnosis, including CSF evaluation, and antimicrobial therapy in infants less than 2 months of age presenting an isolated fever.

J Bacteriol, 2000 Sep, 182(17), 4696 - 703
Microarray-based identification of a novel Streptococcus pneumoniae regulon controlled by an autoinduced peptide; de Saizieu A et al.; We have identified in the Streptococcus pneumoniae genome sequence a two-component system (TCS13, Blp {bacteriocin-like peptide}) which is closely related to quorum-sensing systems regulating cell density-dependent phenotypes such as the development of genetic competence or the production of antimicrobial peptides in lactic acid bacteria . In this study we present evidence that TCS13 is a peptide-sensing system that controls a regulon including genes encoding Blps . Downstream of the Blp TCS (BlpH R) we identified open reading frames (blpAB) that have the potential to encode an ABC transporter that is homologous to the ComA/B export system for the competence-stimulating peptide ComC . The putative translation product of blpC, a small gene located downstream of blpAB, has a leader peptide with a Gly-Gly motif . This leader peptide is typical of precursors processed by this family of transporters . Microarray-based expression profiling showed that a synthetic oligopeptide corresponding to the processed form of BlpC (BlpC*) induces a distinct set of 16 genes . The changes in the expression profile elicited by synthetic BlpC* depend on BlpH since insertional inactivation of its corresponding gene abolishes differential gene induction . Comparison of the promoter regions of the blp genes disclosed a conserved sequence element formed by two imperfect direct repeats upstream of extended -10 promoter elements . We propose that BlpH is the sensor for BlpC* and the conserved sequence element is a recognition sequence for the BlpR response regulator.

Int J Syst Evol Microbiol, 2000 Jul, 50 Pt 4, 1425 - 34
Streptococcus infantarius sp . nov., Streptococcus infantarius subsp . infantarius subsp . nov . and Streptococcus infantarius subsp . coli subsp . nov., isolated from humans and food; Schlegel L et al.; Eighteen strains isolated from human specimens or from food products were characterized as atypical variants of mannitol-negative Streptococcus bovis . They were tested for extended biochemical criteria, ribotyping and DNA-DNA hybridization in order to define their taxonomic status . These strains were demonstrated to constitute a DNA relatedness group that includes strains of DNA group 4 of Farrow et al . (1984) . Comparative analysis of 16S rRNA sequences demonstrated that these strains represent a new species which belongs to the Streptococcus bovis/Streptococcus equinus complex and which has been provisionally named S . infantarius by Bouvet et al . (1997) . Biotyping and ribotyping allowed differentiation of these strains from the aesculin-positive strains of S . bovis belonging to the previously described biotypes I, II.1 and II.2 . The results of the ribotyping and hybridization assays demonstrated the presence of two different DNA subgroups within the 18 strains . On the basis of these data, the names S . infantarius subsp . infantarius (aesculin-negative for five strains out of seven, including the type strain HDP 90056T = NCDO 599T) and S . infantarius subsp . coli (aesculin-positive, reference strain HDP 90248 = NCDO 2620) are proposed as the names for these two subspecies within the S . infantarius species.

J Mol Microbiol Biotechnol, 2000 Apr, 2(2), 225 - 33
Genetic characterization of gram-positive homologs of the XerCD site-specific recombinases; Chalker AF et al.; Homologs of the XerCD enzymes, which in Escherichia coli have been shown to be responsible for resolving chromosomal multimers prior to chromosome segregation, were identified in the genomes of Staphylococcus aureus and Streptococcus pneumoniae . Phylogenetic and conservation pattern analysis suggests that the S . aureus gene products are orthologs of XerC and D . A S . aureus xerC null mutant displayed in vitro characteristics consistent with the segregation defect reported for E . coli xer mutants, and was found to be attenuated in a murine infection model . Strikingly, the S . aureus xerD gene appears to be absolutely required for viability, and may therefore be the first example of an essential gene of the lambda integrase family . In contrast, phylogenetic and conservation pattern analysis show that the S . pneumoniae gene products are more closely related to phage integrases than to XerCD . S . pneumoniae xer1, 2 and 3 null mutants were each found to be attenuated in a murine infection model, suggesting that they may control processes which affect virulence.

J Virol, 2000 Sep, 74(17), 7803 - 13
MM1, a temperate bacteriophage of the type 23F Spanish/USA multiresistant epidemic clone of Streptococcus pneumoniae: structural analysis of the site-specific integration system; Gindreau E et al.; We have characterized a temperate phage (MM1) from a clinical isolate of the multiply antibiotic-resistant Spanish/American 23F Streptococcus pneumoniae clone (Spain(23F)-1 strain) . The 40-kb double-stranded genome of MM1 has been isolated as a DNA-protein complex . The use of MM1 DNA as a probe revealed that the phage genome is integrated in the host chromosome . The host and phage attachment sites, attB and attP, respectively, have been determined . Nucleotide sequencing of the attachment sites identified a 15-bp core site (5'-TTATAATTCATCCGC-3') that has not been found in any bacterial genome described so far . Sequence information revealed the presence of an integrase gene (int), which represents the first identification of an integrase in the pneumococcal system . A 1.5-kb DNA fragment embracing attP and the int gene contained all of the genetic information needed for stable integration of a nonreplicative plasmid into the attB site of a pneumococcal strain . This vector will facilitate the introduction of foreign genes into the pneumococcal chromosome . Interestingly, DNAs highly similar to that of MM1 have been detected in several clinical pneumococcal isolates of different capsular types, suggesting a widespread distribution of these phages in relevant pathogenic strains.

J Antimicrob Chemother, 2000 Aug, 46(2), 235 - 40
Intravenous infusion of erythromycin inhibits CXC chemokine production, but augments neutrophil degranulation in whole blood stimulated with Streptococcus pneumoniae; Schultz MJ et al.; Macrolides may influence the inflammatory response to an infection by mechanisms that are unrelated to their antimicrobial effect . Indeed, erythromycin and other macrolides inhibit cytokine production and induce degranulation of neutrophils in vitro . CXC chemokines are small chemotactic cytokines that specifically influence neutrophil functions . To determine the effect of a clinically relevant dose of erythromycin on the production of CXC chemokines and neutrophil degranulation, six healthy humans received a 30 min iv infusion of erythromycin (1000 mg) . Whole blood obtained before and at various times after the infusion was stimulated ex vivo with heat-killed Streptococcus pneumoniae . Ex vivo production of the CXC chemokines interleukin 8 (IL-8) and epithelial cell-derived neutrophil attractant 78 (ENA-78), in whole blood obtained after erythromycin infusion, was lower than that in blood drawn before erythromycin infusion (maximum inhibition post-infusion: 32.9 +/- 6.5% and 35.2 +/- 12.6% decrease in production, respectively, expressed as percentage change relative to production before infusion of erythromycin, both P < 0.05) . In contrast, infusion of erythromycin was associated with an enhanced capacity of whole blood to release the neutrophil degranulation products bactericidal/permeability increasing protein (BPI), human neutrophil elastase (HNE) and human lactoferrin (HLF) upon stimulation with S . pneumoniae . Effects of erythromycin were greatest 4 h after infusion was stopped, when BPI, HNE and HLF concentrations were increased by +107.6 +/- 33.5%, +134.7 +/- 34.8% and +205.9 +/- 55.9 %, respectively (expressed as percentage change relative to production before infusion of erythromycin) (all P < 0 . 05) . These results indicate the ability of erythromycin to reduce CXC chemokine production and to enhance neutrophil degranulation in human blood.

J Child Adolesc Psychopharmacol, 2000 Summer, 10(2), 133 - 45
Infection-triggered anorexia nervosa in children: clinical description of four cases; Sokol MS; BACKGROUND: Anorexia nervosa (AN) is a serious illness with no definitive treatment . Clinical and research evidence led to the hypothesis that some children with AN may have a pediatric autoimmune neuropsychiatric disorder associated with streptococcus (PANDAS), similar in pathogenesis to other hypothesized PANDAS disorders . METHODS: Four youngsters (ages, 11-15 years) with PANDAS AN were treated with an open trial of antibiotics, in addition to conventional treatment . They were evaluated for eating disorder and obsessive-compulsive symptoms, and for weight gain . Evidence of streptococcal infection came from clinical evaluation, throat cultures, and two serological tests: anti-deoxyribonuclease B (anti-DNase B) and anti-streptolysin O (ASO) titers . The "rheumatic" marker D8/17 was also measured . This B-cell alloantigen is associated, in several publications, with poststreptococcal autoimmunity: Rheumatic fever (RF), Sydenham's chorea (SC), and possibly PANDAS obsessive compulsive disorder (OCD) and tic disorders . RESULTS: There was clinical evidence of possible antecedent streptococcal infection in all four patients, two of whom had comorbid OCD, with possible infection-triggered AN . All four had the rheumatic marker: A percentage of D8/17-positive B cells of 28-38%, with a mean of 33% (12% or more is considered positive for the marker) . The patients responded to conventional treatment plus antibiotics with weight restoration and decreased eating disorder and obsessive-compulsive symptoms . Three needed to gain weight and did so . CONCLUSIONS: There may be a link between infectious disease and some cases of AN, which raises the possibility of new treatment.

Srp Arh Celok Lek, 2000 Mar-Apr, 128(3-4), 94 - 6
{Massive pneumonia with severe acute respiratory insufficiency after chicken pox in a female patient}; Nagorni-Obradovic Lj et al.; A female patient who developed massive bilateral pneumonia with severe respiratory insufficiency during recovery from varicella, is presented . Blood serologic analyses detected the cause of infection--Mycoplasma pneumoniae, while Streptococcus pneumoniae was isolated by bacteriological examination of the sputum . M . pneumoniae is a causative agent of acute upper and lower respiratory airway infections with a frequently mild clinical picture . This agent rarely provokes massive pneumonia with severe clinical appearance as described in the patient, who had immunodeficiency due to previous infection with Varicella zoster virus.

Nat Med, 2000 Aug, 6(8), 929 - 32
Fetal immunization by a DNA vaccine delivered into the oral cavity; Gerdts V et al.; Infectious diseases are the main cause of neonatal morbidity and mortality in humans . The World Health Organization estimated that in 1995 approximately 8 million infants died within the first year of life from infectious diseases, including 5 million during the first week of life . Some of the salient pathogens involved include herpes simplex virus, human immunodeficiency virus, hepatitis B virus, human cytomegalovirus, group B streptococcus, hemophilus and chlamydia . Infection with these pathogens usually occurs at the end of pregnancy, during birth or by breastfeeding . To reduce the risk of disease transmission, caesarian sections, prophylactic treatment with antibiotics or maternal antiviral therapy during the last trimester are used where available, together with improved neonatal care . None of these approaches, however, completely eliminates the risk of neonatal infection . Therefore, active or passive immunization of the fetus might represent an effective approach to reduce the high risk of neonatal diseases . Here, we demonstrate that a single immunization with a DNA vaccine delivered into the amniotic fluid in the oral cavity induces high serum antibody titers and a cell-mediated immune response, combined with induction of local immunity in the oral cavities of fetal lambs.

Microbiology, 2000 Aug, 146 ( Pt 8), 1923 - 31
Environmental regulation of glycosidase and peptidase production by Streptococcus gordonii FSS2; Harty DW et al.; The synthesis of cell-associated and secreted proteins by Streptococcus gordonii FSS2, an infective endocarditis (IE) isolate, was influenced by both environmental pH and carbon source . Controlling the pH at 7.5 in stirred batch cultures showed that cell-associated and secreted protein concentrations were increased during late exponential and stationary phase by 68% and 125%, respectively, compared with similar cultures without pH control . The expression of five glycosidase and eight peptidase activities were examined using fluorogen-labelled synthetic substrates . Enzyme activities were significantly down-regulated during exponential growth, increasing during stationary phase (P<0.01) whether the culture pH was controlled at pH 7.5 or allowed to fall naturally to pH 4.4 . Culture-supernatant activities were significantly increased (P<0.05) when the pH was maintained at 6.0 or 7.5, indicating modulation of enzyme activity by pH . Growth under nitrogen-limitation/glucose-excess conditions resulted in a significant repression of cell-associated glycosidase activities (P<0.01), whilst in the supernatant, activities were generally reduced . The expression of peptidase activities in the culture supernatant did not significantly change . The results suggest a possible role for catabolite repression by glucose in regulating enzyme expression . When S . gordonii FSS2 was cultured with 50% (v/v) added heat-inactivated foetal bovine serum, several cell-associated enzyme activities increased initially but were then reduced as the culture time was extended to 116 h . Culture-supernatant enzyme activities (N-acetyl-beta-D-glucosaminidase, N-acetyl-beta-D-galactosaminidase, thrombin, Hageman factor, collagenase and chymotrypsin), however, were significantly increased (P<0.01) over the same time period . The findings indicated that most of the important glycosidases synthesized by S . gordonii FSS2 were down-regulated by acid growth conditions and may also be subject to catabolite repression by glucose but conversely may be up-regulated by growth in serum . These results may have implications for streptococcal growth in an IE vegetation and in the mouth between meals or during sleep.

Microbiology, 2000 Aug, 146 ( Pt 8), 1913 - 21
Interactions between Streptococcus suis serotype 2 and different epithelial cell lines; Lalonde M et al.; Streptococcus suis is an important swine pathogen responsible for cases of sudden death, septicaemia, meningitis, endocarditis and pneumonia . It is also recognized as a zoonotic agent in people occupationally exposed to pigs or pig products . Knowledge on virulence factors of S . suis serotype 2 is limited and the pathogenesis of the infection is poorly understood . It has been suggested that the disease due to S . suis serotype 2 begins with colonization of the nasopharyngeal epithelium, followed by either spread within the respiratory tract or invasion of the bloodstream . The mechanisms involved in the access of bacteria from the bloodstream to the central nervous system are unknown . It is possible that epithelial cells of the choroid plexus also play an important role in the pathogenesis of the meningitis . Different interactions (adhesion, invasion and toxic effects) of S . suis serotype 2 with epithelial cell lines {LLC-PK1, PK(15), A549, HeLa and MDCK} were studied and compared to those of a human pathogen which also causes meningitis, group B Streptococcus (GBS) . The results showed that S . suis serotype 2, in contrast to GBS, is able to adhere to but not to invade epithelial cells . The adhesin(s) involved seem(s) to be partially masked by the capsule and are a part of the cell wall . The haemolysin produced by S . suis serotype 2 is responsible for a toxic effect observed on epithelial cells . The results described give additional evidence that pathogenesis of the infection differs between S . suis and GBS . In particular, it is possible that suilysin-positive S . suis strains use adherence and cell injury, as opposed to direct cellular invasion, as part of a complicated multistep process which leads to bacteraemia and meningitis in pigs.

Mol Microbiol, 2000 Jun, 36(6), 1306 - 18
Generation of a mature streptococcal cysteine proteinase is dependent on cell wall-anchored M1 protein; Collin M et al.; In the present study, we have generated a mutant strain of Streptococcus pyogenes, MC25, which lacks M protein on its surface, and we demonstrate that this strain is unable to generate a mature 28 kDa cysteine proteinase . Furthermore, we show that S . pyogenes bacteria of M1 serotype are dependent on cell wall-anchored M protein to cleave the secreted zymogen into a mature cysteine proteinase . We also show that MC25 secretes a 40 kDa zymogen, having a conformation different from that secreted by wild-type bacteria . We provide data showing that the cleavage site is not blocked but, presumably, the active site is . This suggests that M protein, when anchored to the cell wall, is involved in the unfolding of the zymogen and generation of a mature cysteine proteinase that can be activated under reducing conditions . Our data add new aspects to the interaction between two important virulence factors of S . pyogenes, the streptococcal cysteine proteinase and M protein.

Mol Microbiol, 2000 Jun, 36(6), 1279 - 92
Global analysis of transcription kinetics during competence development in Streptococcus pneumoniae using high density DNA arrays; Rimini R et al.; The kinetics of global changes in transcription patterns during competence development in Streptococcus pneumoniae was analysed with high-density arrays . Four thousand three hundred and one clones of a S . pneumoniae library, covering almost the entire genome, were amplified by PCR and gridded at high density onto nylon membranes . Competence was induced by the addition of CSP (competence stimulating peptide) to S . pneumoniae cultures grown to the early exponential phase . RNA was extracted from samples at 5 min intervals (for a period of 30 min) after the addition of CSP . Radiolabelled cDNA was generated from isolated total RNA by random priming and the probes were hybridized to identical high density arrays . Genes whose transcription was induced or repressed during competence were identified . Most of the genes previously known to be competence induced were detected together with several novel genes that all displayed the characteristic transient kinetics of competence-induced genes . Among the newly identified genes many have suggested functions compatible with roles in genetic transformation . Some of them may represent new members of the early or late competence regulons showing competence specific consensus sequences in their promoter regions . Northern experiments and mutational analysis were used to confirm some of the results.

FEMS Microbiol Lett, 2000 Aug 15, 189(2), 281 - 4
NeuD plays a role in the synthesis of sialic acid in Escherichia coli K1; Daines DA et al.; The polysialic acid capsule of Escherichia coli K1 is an essential virulence determinant . The kps gene cluster, which encodes the proteins necessary for polymer synthesis and transport, is divided into three functional regions . In this report, we present evidence that the neuD gene from region 2 is involved in sialic acid synthesis . A non-polar chromosomal deletion in neuD was constructed . The defect was complemented by neuD in trans or by the addition of exogenous sialic acid . A NeuD homologue, Neu(III)D, from serotype III Streptococcus agalactiae (GBS) also restored capsule expression to the neuD deletion strain . These data confirm the role of neuD in E . coli sialic acid capsule synthesis and demonstrate that the neu(III)D homologue from GBS shares a similar enzymatic function.

J Periodontal Res, 2000 Jun, 35(3), 172 - 7
Effect of the interleukin-1 genotype on monocyte IL-1beta expression in subjects with adult periodontitis; Mark LL et al.; An association has been reported between polymorphisms in the genes encoding IL-1alpha (-889) and IL-1beta (+3953) (periodontitis susceptibility trait, PST), and an increased severity of periodontitis (18) . The IL-1beta polymorphism was reported to correlate with increased IL-1beta expression by monocytes in response to bacterial stimulants . In the present study, we determined if PST positive subjects with periodontitis exhibit elevated production of IL-1beta, compared to PST negative periodontitis patients . Peripheral blood monocytes were obtained from 10 PST+ and 10 PST- age- and disease-balanced subjects with adult forms of periodontitis . Monocytes were cultured with a panel of bacterial stimulants, including Escherichia coli and Porphyromonas gingivalis LPS, and whole formalinized periodontal pathogens P . gingivalis, Bacteroides forsythus and Prevotella intermedia, and health-associated organisms Veillonella parvula and Streptococcus sanguis . Our results demonstrate that monocytes from PST+ and PST- patients showed no significant differences in IL-1beta production in response to any stimulant tested . In addition, the periodontal pathogens P . gingivalis, B . forsythus and P . intermedia failed to stimulate higher IL-1beta responses compared to health-associated species V . parvula and S . sanguis . A marked interindividual variation in production of IL-1beta was seen, with high, low and intermediate responders present in both PST+ and PST- groups . We conclude that genetic loci other than the PST polymorphisms are also important regulators of monocyte IL-1 responses.

Cornea, 2000 Jul, 19(4), 455 - 8
Infectious keratitis in climatic droplet keratopathy; Sridhar MS et al.; PURPOSE: To report the ulcer characteristics, microbiologic data, and outcome of infectious keratitis associated with climatic droplet keratopathy (CDK), suggesting that CDK is a predisposing factor for infectious keratitis . METHODS: Medical records of 32 patients (34 eyes) in whom infectious keratitis was seen in association with CDK were retrospectively reviewed . Data were collected regarding the nature of CDK lesions, infiltrate characteristics, organisms isolated, and outcome . RESULTS: CDK was peripheral in 16 (47.1%) eyes, central in 8 (23.5%), and diffuse in 10 (29.4%) . The CDK lesions were nodular and elevated in all eyes . The infiltrate was adjacent to the CDK lesions in 28 eyes (82.4%) . The infiltrate size (widest dimension) ranged 2-6 mm in 18 eyes (52.9%) and was >6 mm in 7 (20.5%) . The infiltrate was full thickness in 15 eyes (44.1%) and was involving up to the middle third of the corneal stroma in another 18 (52.8%) . Hypopyon was seen in all . Bacteria were commonly isolated . Staphylococcus epidermidis (six eyes) and Streptococcus pneumoniae (five eyes) were the common bacteria isolated . Resolution with medical treatment was seen in 20 (58.8%) eyes . CONCLUSIONS: CDK is a predisposing factor for infectious keratitis . Treatment should be considered for advanced and nodular lesions, even if they are peripheral, to prevent infectious keratitis.

Pathophysiology, 2000 Jul, 7(2), 143 - 148
Effect of static magnetic fields on bacteria: Streptococcus mutans, Staphylococcus aureus, and Escherichia coli; Kohno M et al.; Biological effect of static magnetic field was investigated by using ferrite magnets to conduct a magnetic field exposure experiment on three species of bacteria: Streptococcus mutans, Staphylococcus aureus, and Escherichia coli . The effects were evaluated by culturing the bacteria and determining their growth rate, the maximum numbers of bacteria, and {3H}-thymidine incorporation . The results showed that the ferrite magnet caused strength-dependent decreases in the growth rate and growth maximum number of bacteria for S . mutans and S . aureus when cultured under anaerobic conditions, but that their growth was not inhibited under aerobic conditions . In addition, {3H}-thymidine was added after culturing each of the species of bacteria for 18 h . After that, culture was continued until 24 h, and changes in {3H}-thymidine incorporation were investigated . But no effect of the magnetic fields was detected . These findings suggested that oxygen related to growth the cases of S . mutans, S . aureus . However, no growth effects were detected on E . coli cultures.

Can Fam Physician, 2000 Jul, 46, 1460 - 6
Necrotizing fasciitis secondary to group A streptococcus . Morbidity and mortality still high; Leitch HA et al.; OBJECTIVE: To update physicians on Group A streptococcal necrotizing fasciitis, including current methods of diagnosis and treatment . QUALITY OF EVIDENCE: Current literature (1990-1998) was searched via MEDLINE using the MeSH headings necrotizing fasciitis, toxic shock syndrome, and Streptococcus . Articles were selected based on clinical relevance and design . Most were case reports, case series, or population-based surveys . There were no randomized controlled trials . MAIN MESSAGE: The hallmark of clinical diagnosis of necrotizing fasciitis is pain out of proportion to physical findings . Suspicion of underlying soft tissue infection should prompt urgent surgical examination . Therapy consists of definitive excisional surgical debridement in conjunction with high-dose intravenous penicillin G and clindamicin . Risk factors for mortality include advanced age, underlying illness, hypotension, and bacteremia . CONCLUSION: Necrotizing soft tissue infections due to Group A streptococcus might be increasing in frequency and aggression . Overall mortality remains high (20% to 34% in larger series) . Clinical diagnosis requires a high level of suspicion and should prompt urgent surgical referral.

J Immunol, 2000 Aug 15, 165(4), 2306 - 12
Development of streptococcal pyrogenic exotoxin C vaccine toxoids that are protective in the rabbit model of toxic shock syndrome; McCormick JK et al.; Streptococcal pyrogenic exotoxin C (SPE C) is a superantigen produced by many strains of Streptococcus pyogenes that (along with streptococcal pyrogenic exotoxin A) is highly associated with streptococcal toxic shock syndrome (STSS) and other invasive streptococcal diseases . Based on the three-dimensional structure of SPE C, solvent-exposed residues predicted to be important for binding to the TCR or the MHC class II molecule, or important for dimerization, were generated . Based on decreased mitogenic activity of various single-site mutants, the double-site mutant Y15A/N38D and the triple-site mutant Y15A/H35A/N38D were constructed and analyzed for superantigenicity, toxicity (lethality), immunogenicity, and the ability to protect against wild-type SPE C-induced STSS . The Y15A/N38D and Y15A/H35A/N38D mutants were nonmitogenic for rabbit splenocytes and human PBMCs and nonlethal in two rabbit models of STSS, yet both mutants were highly immunogenic . Animals vaccinated with the Y15A/N38D or Y15A/H35A/N38D toxoids were protected from challenge with wild-type SPE C . Collectively, these data indicate that the Y15A/N38D and Y15A/H35A/N38D mutants may be useful as toxoid vaccine candidates.

Mol Biochem Parasitol, 2000 Jun, 109(1), 17 - 23
Effects of interruption of apicoplast function on malaria infection, development, and transmission; Sullivan M et al.; A chloroplast-like organelle is present in many species of the Apicomplexa phylum . We have previously demonstrated that the plastid organelle of Plasmodium faciparum is essential to the survival of the blood-stage malaria parasite in culture . One known function of the plastid organelle in another Apicomplexan, Toxoplasma gondii, involves the formation of the parasitophorous vacuole . The effects of interruption of plastid function on sporozoites and sexual-stage parasites have not been investigated . In our previous studies of the effects of thiostrepton, a polypeptide antibiotic from streptococcus spp., on erythrocytic schizongony of the human malaria P . falciparium, we found that this antibiotic appears to interact with the guanosine triphosphatase (GTPase) binding domain of the organellar large subunit ribosomal RNA, as it does in bacteria . We investigate here the effects of this drug on life-cycle stages of the malaria parasite in vivo . Preincubation of mature infective sporozoites with thiostrepton has no observable effect on their infectivity . Sporozoite infection both by mosquito bite and sporozoite injection was prevented by pretreatment of mice with thiostrepton . Thiostrepton eliminates infection with erythrocytic forms of Plasmodium berghei in mice . Clearance of infected red blood cells follows the delayed kinetics associated with drugs that interact with the apicoplast . Thiostrepton treatment of infected mice reduces transmission of parasites by more than ten-fold, indicating that the plastid has a role in sexual development of the parasite . These results indicate that the plastid function is accessible to drug action in vivo and important to the development of both sexual and asexual forms of the parasite.

Appl Environ Microbiol, 2000 Aug, 66(8), 3221 - 9
Purification and biochemical characterization of mutacin I from the group I strain of Streptococcus mutans, CH43, and genetic analysis of mutacin I biosynthesis genes; Qi F et al.; Previously, we reported isolation and characterization of mutacin III and genetic analysis of mutacin III biosynthesis genes from the group III strain of Streptococcus mutans, UA787 (F . Qi, P . Chen, and P . W . Caufield, Appl . Environ . Microbiol . 65:3880-3887, 1999) . During the same process of isolating the mutacin III structural gene, we also cloned the structural gene for mutacin I . In this report, we present purification and biochemical characterization of mutacin I from the group I strain CH43 and compare mutacin I and mutacin III biosynthesis genes . The mutacin I biosynthesis gene locus consists of 14 genes in the order mutR, -A, -A', -B, -C, -D, -P, -T, -F, -E, -G, orfX, orfY, orfZ . mutA is the structural gene for mutacin I, while mutA' is not required for mutacin I activity . DNA and protein sequence analysis revealed that mutacins I and III are homologous to each other, possibly arising from a common ancestor . The mature mutacin I is 24 amino acids in size and has a molecular mass of 2, 364 Da . Ethanethiol modification and peptide sequencing of mutacin I revealed that it contains six dehydrated serines, four of which are probably involved with thioether bridge formation . Comparison of the primary sequence of mutacin I with that of mutacin III and epidermin suggests that mutacin I likely has the same bridging pattern as epidermin.

Pediatr Infect Dis J, 2000 Jul, 19(7), 608 - 12
Colonization by Streptococcus penumoniae in human immunodeficiency virus-infected children; Polack FP et al.; OBJECTIVE: Children with HIV infection are particularly susceptible to invasive pneumococcal disease, yet the effect of HIV infection and its medical management on colonization and resistance to antibiotics are poorly described . To provide a basis for medical practice, we determined the prevalence of nasopharyngeal colonization and antibiotic resistance of Streptococcus pneumoniae in children with HIV infection . METHODS: Cross-sectional prevalence sample of children attending the pediatric HIV and pulmonary clinics to examine nasopharyngeal colonization with S . pneumoniae and antibiotic resistance to beta-lactams and trimethoprim-sulfamethoxazole (T/S) . Subjects were matched by age and date of clinic visit . RESULTS: The colonization rate with S . pneumoniae of HIV-infected and -indeterminate children was equal to that of controls (20% vs . 19%) . HIV infection, CDC staging or receipt of oral antibiotic therapy did not affect colonization . Isolates from HIV-infected and -indeterminate children were less likely to be penicillin-resistant than those from controls (18% vs . 50%) . There was no difference in pneumococcal resistance to T/S among isolates from subjects and controls, despite 72% T/S use in the HIV clinic . CONCLUSION: Colonization with S . pneumoniae in HIV disease is no different from that of comparable children . The high incidence of pneumococcal disease and prophylaxis with T/S are not related to nasopharyngeal colonization . Antibiotic prophylaxis of HIV-infected children does not necessarily lead to increased resistance of S . pneumoniae.

Intensive Care Med, 2000 May, 26(5), 526 - 31
Late steroid therapy in primary acute lung injury; Varpula T et al.; OBJECTIVE: To investigate the effect of steroid treatment in the late phase of primary acute lung injury (ALI) with special emphasis on pneumococcal pneumonia . DESIGN: Retrospective study . SETTING: Multidisciplinary intensive care unit (ICU) in a university hospital . PATIENTS: Of 31 patients with primary ALI requiring mechanical ventilation for more than 10 days, 16 were treated with methylprednisolone and 15 served as controls . MEASUREMENTS AND RESULTS: Steroid and control groups were comparable regarding demographic data, APACHE II score, Multiple Organ Dysfunction Score (MODS), and PaO2/FiO2-ratio on admission to ICU . The mean start of steroid therapy was 9.7 days after establishment of respiratory failure, and values for control patients were registered on day 10 . The PaO2/FiO2 ratio improved significantly within 3 days after the start of steroid therapy, and MODS and C-reactive protein decreased concurrently . No differences in mortality, in length of ICU stay, or in length of mechanical ventilation were detectable . In a subgroup analysis, for patients with Streptococcus pneumoniae pneumonia, beneficial change in physiological variables was evident . CONCLUSIONS: In patients with primary ALI, steroid therapy, started 10 days after the start of mechanical ventilation, improves gas exchange and is associated with a decrease in multiorgan dysfunction.

Eur J Pediatr, 2000 Jul, 159(7), 527 - 9
Streptococcus pyogenes meningitis: report of a case and review of the literature; Berner R et al.; Streptococcus pyogenes is a very uncommon cause of bacterial meningitis beyond the neonatal period . A case report and a review of the recent literature is presented . We report on a previously healthy 7-year-old boy who developed S . pyogenes meningitis following a 2-day history of otitis media . A CT scan revealed right-sided mastoiditis as a possible focus of infection . The patient was treated with penicillin G for 14 days . The clinical course was uneventful, and the recovered without sequelae . By means of the polymerase chain reaction, the presence of streptococcal pyrogenic exotoxin (SPE) B and SPE C, but not SPE A genes was discovered from the bacterial DNA . CONCLUSION: Streptococcus pyogenes is a rare cause of bacterial meningitis but has to be considered as the causative pathogen beyond the neonatal period.

J Clin Microbiol, 2000 Aug, 38(8), 2814 - 8
Rapid automated antimicrobial susceptibility testing of Streptococcus pneumoniae by use of the bioMerieux VITEK 2; Jorgensen JH et al.; The VITEK 2 is a new automated instrument for rapid organism identification and susceptibility testing . It has the capability of performing rapid susceptibility testing of Streptococcus pneumoniae with specially configured cards that contain enriched growth medium and antimicrobial agents relevant for this organism . The present study compared the results of testing of a group of 53 challenge strains of pneumococci with known resistance properties and a collection of clinical isolates examined in two study phases with a total of 402 and 416 isolates, respectively, with a prototype of the VITEK 2 . Testing was conducted in three geographically separate laboratories; the challenge collection was tested by all three laboratories, and the unique clinical isolates were tested separately by the individual laboratories . The VITEK 2 results of tests with 10 antimicrobial agents were compared to the results generated by the National Committee for Clinical Laboratory Standards reference broth microdilution MIC test method . Excellent interlaboratory agreement was observed with the challenge strains . The overall agreement within a single twofold dilution of MICs defined by the VITEK 2 and reference method with the clinical isolates was 96.3%, although there were a number of off-scale MICs that could not be compared . The best agreement with the clinical isolates was achieved with ofloxacin and chloramphenicol (100%), and the lowest level of agreement among those drugs with sufficient on-scale MICs occurred with trimethoprim-sulfamethoxazole (89.7%) . Overall there were 1.3% very major, 6.6% minor, and no major interpretive category errors encountered with the clinical isolates, although >80% of the minor interpretive errors involved only a single log(2) dilution difference . The mean time for generation of susceptibility results with the clinical isolates was 8.1 h . The VITEK 2 provided rapid, reliable susceptibility category determinations with both the challenge and clinical isolates examined in this study.

Crit Care Med, 2000 Jul, 28(7), 2277 - 82
Interleukin-1 receptor antagonist production during infectious and noninfectious systemic inflammatory response syndrome; Marie C et al.; OBJECTIVE: To analyze the levels of circulating and cell-associated forms of interleukin-1 receptor antagonist (IL-1ra) and the spontaneous and the lipopolysaccharide- or streptococcus-induced ex vivo production of IL-1ra by isolated neutrophils . DESIGN: Cohort study . SETTING: A collaborative study between an intensive care unit and a research laboratory . PATIENTS: Septic patients (those with infectious systemic inflammatory response syndrome {SIRS}) and patients undergoing cardiac surgery with cardiopulmonary bypass (noninfectious SIRS) . MEASUREMENTS AND MAIN RESULTS: Both noninfectious and infectious SIRS patients had enhanced levels of plasma IL-1ra . In septic patients, the increased level of IL-1ra associated with circulating leukocytes reflected the higher number of circulating neutrophils, because these cells, as well as peripheral blood mononuclear cells, contained similar levels of cell-associated forms of IL-1ra than those found at homeostasis in healthy controls . The analysis of the in vitro production of IL-1ra by neutrophils showed a decreased capacity of these cells to release the secreted form of IL-1ra on activation in all patients when compared with that capacity in healthy controls . In contrast, the production of the intracellular forms of IL-1ra was not altered in septic patients, but it was diminished in post-cardiopulmonary bypass patients . CONCLUSIONS: The capacity of releasing IL-1ra by activated neutrophils from infectious or noninfectious SIRS patients was diminished . In contrast, the accumulation of intracellular IL-1ra in septic patients was not modified when compared with that in healthy controls . These ex vivo data illustrate that a different gene regulation of the secreted and intracellular forms of IL-1 ra occurs during a pathologic situation like sepsis.

Pediatrics, 2000 Aug, 106(2 Pt 1), 256 - 63
Neonatal sepsis workups in infants >/=2000 grams at birth: A population-based study; Escobar GJ et al.; BACKGROUND: Few data are available on the outcome of neonatal sepsis evaluations in an era when intrapartum antibiotic therapy is common . METHODS: We identified all newborns weighing >/=2000 g at birth who were ever evaluated for suspected bacterial infection at 6 Kaiser Permanente hospitals between October 1995 and November 1996, reviewed their records and laboratory data, and tracked them to 1 week after discharge . We analyzed the relationship between key predictors and the presence of neonatal bacterial infection . RESULTS: Among 18 299 newborns >/=2000 g without major congenital anomalies, 2785 (15.2%) were evaluated for sepsis with a complete blood count and/or blood culture . A total of 62 (2.2%) met criteria for proven, probable, or possible bacterial infection: 22 (.8%) had positive cultures and 40 (1.4%) had clinical evidence of bacterial infection . We tracked all but 10 infants (.4%) to 7 days postdischarge . There were 67 rehospitalizations (2.4%; 2 for group B streptococcus bacteremia) . Among 1568 infants who did not receive intrapartum antibiotics, initial asymptomatic status was associated with decreased risk of infection (adjusted odds ratio {AOR}:.26; 95% confidence interval {CI}:.11-.63), while chorioamnionitis (AOR: 2 . 40; 95% CI: 1.15-5.00), low absolute neutrophil count (AOR: 2.84; 95% CI: 1.50-5.38), and meconium-stained amniotic fluid (AOR: 2.23; 95% CI: 1.18-4.21) were associated with increased risk . Results were similar among 1217 infants who were treated, except that maternal chorioamnionitis was not significantly associated with neonatal infection . CONCLUSIONS: The risk of bacterial infection in asymptomatic newborns is low . Evidence-based observation and treatment protocols could be defined based on a limited set of predictors: maternal fever, chorioamnionitis, initial neonatal examination, and absolute neutrophil count . Many missed opportunities for treating mothers and infants exist.

Adolesc Med, 2000 Jun, 11(2), 427 - 38
Current challenges in antibiotic resistance; Hand WL; The striking, widespread increase in bacterial resistance to antibiotics is an issue of great concern . Worldwide emergence of antibiotic resistances in our common gram-positive coccal pathogens is probably the most serious problem we have in the realm of bacterial infections . The most important of these organisms are penicillin-resistant Streptococcus pneumoniae, vancomycin-resistant Enterococcus, and methicillin- (and now vancomycin-) resistant Staphylococcus aureus . Although known by the above names, all of these organisms are multidrug-resistant . Beta-lactam and vancomycin resistances in gram-positive cocci are caused by altered cell wallnbinding sites with decreased affinity for the drug . Another serious problem is that of resistance in certain gram-negative bacilli due to extended-spectrum beta-lactamase production . These antibiotic resistances in common pathogens have made antimicrobial therapy of many infections extremely difficult or virtually impossible in some instances . The extensive, and often inappropriate, use of antibiotics in the U.S . and worldwide is the major factor in the emergence and spread of antimicrobial resistance . Microbial mechanisms, epidemiology, clinical importance, treatment, and prevention of these antibiotic resistance problems are discussed.

Adv Ther, 2000 Jan-Feb, 17(1), 14 - 26
Clarithromycin suspension vs penicillin V suspension in children with streptococcal pharyngitis; McCarty J et al.; Clarithromycin, an advanced-generation macrolide antibiotic, has demonstrated excellent in vitro activity against group A beta-hemolytic streptococcus (GABHS) . Potent activity against Streptococcus pyogenes and a favorable pharmacokinetic profile have made it a reasonable alternative for treatment of patients with streptococcal pharyngitis . The safety and efficacy of clarithromycin and penicillin V were compared in a randomized, investigator-blind study . Children 6 months to 12 years of age received 5 days of clarithromycin suspension 7.5 mg/kg twice daily (n = 268) or 10 days of penicillin V suspension 13.3 mg/kg three times daily (n = 260) . Patients were evaluated for signs and symptoms of pharyngitis, and throat swabs for culture were obtained prior to therapy, at the end of therapy, and at follow-up . Clarithromycin and penicillin V produced comparable rates of clinical success (cure + improvement) at the posttreatment (97% and 94%) and follow-up (81% and 82%) evaluations . The GABHS eradication rate, however, was significantly higher with clarithromycin (94% vs 78%, P < .001) . Both drugs were well tolerated; gastrointestinal complaints were similar and mild . Resistance did not occur with the short course of clarithromycin or the standard regimen of penicillin V . Five days' treatment with clarithromycin was superior to 10 days of penicillin in eradicating S . pyogenes.

Curr Microbiol, 2000 Sep, 41(3), 210 - 3
Antibacterial carbohydrate monoesters suppressing cell growth of Streptococcus mutans in the presence of sucrose; Watanabe T et al.; The growth-inhibitory effect of 23 carbohydrate monoesters synthesized by lipases and proteases were assayed to obtain antibacterial agents that suppress the cell growth of Streptococcus mutans . Among the carbohydrate esters synthesized, galactose and fructose laurates showed the highest growth-inhibitory effect, while the other analogs of hexose laurates showed no antibacterial activity, indicating that configuration of the hydroxyl group in carbohydrate moiety markedly affects the antibacterial activity . The cell growth of S . mutans was suppressed by fructose laurates even in the presence of sucrose . Thus, enzymatic synthesis of carbohydrate esters with different core structures has great potential for developing antibacterial agents applicable to food additives.

Curr Microbiol, 2000 Sep, 41(3), 182 - 6
Deoxyribonuclease activity in Selenomonas ruminantium, Streptococcus bovis, and Bacteroides ovatus; Al-Khaldi SF et al.; Six Selenomonas ruminantium strains (132c, JW13, SRK1, 179f, 5521c1, and 5934e), Streptococcus bovis JB1, and Bacteroides ovatus V975 were examined for nuclease activity as well as the ability to utilize nucleic acids, ribose, and 2-deoxyribose . Nuclease activity was detected in sonicated cells and culture supernatants for all bacteria except S . ruminantium JW13 and 179f sonicated cells . S . ruminantium strains were able to utilize several deoxyribonucleosides, while S . bovis JB1 and B . ovatus V975 showed little or no growth on all deoxyribonucleosides . When S . ruminantium strains 5934e, 132c, JW13, and SRK1 were incubated in medium that contained 15 mm ribose, the major end products were acetate, propionate, and lactate . S . ruminantium 5521c1 and S . bovis JB1 did not grow on ribose, and none of the S . ruminantium strains or S . bovis JB1 grew on 15 mm 2-deoxyribose . In contrast, B . ovatus V975 was able to grow on ribose and 2-deoxyribose . In conclusion, all S . ruminantium strains, S . bovis JB1, and B . ovatus V975 had nuclease activity . However, not all bacteria were able to utilize deoxyribonucleosides, ribose, or 2-deoxyribose.

J Infect Dis, 2000 Aug, 182(2), 509 - 16 Epub 2000 Jul 28.
Short-course antibiotic treatment of 4782 culture-proven cases of group A streptococcal tonsillopharyngitis and incidence of poststreptococcal sequelae; Adam D et al.; A large-scale study with a 1-year follow-up was performed to compare 10 days of penicillin V with a short-course treatment (5 days) of other oral antibiotics in the treatment of group A beta-hemolytic streptococcus (GABHS) tonsillopharyngitis, to evaluate the efficacy and the incidence of poststreptococcal sequelae . The clinical response rates after completion of therapy were 94.5% in the 5-day group and 93.4% in the penicillin group (P<.001, equivalence test) . The GABHS eradication rates were 83.3% in the 5-day group and 84.4% in the penicillin group (P=.022, equivalence test) . Poststreptococcal sequelae were rare (5 patients) and did not occur in the context of this study . The efficacy of 5-day antibiotic regimens was equivalent to 10 days of penicillin V, but resolution of clinical symptoms was faster in the 5-day group (P<.001, Fisher's exact test) . Recurrent tonsillopharyngitis occurs more frequently after treatment with penicillin (P=.03, Fisher's exact test).

J Infect Dis, 2000 Aug, 182(2), 497 - 508 Epub 2000 Jul 19.
C3 as substrate for adhesion of Streptococcus pneumoniae; Smith BL et al.; The ability of choline-binding protein A (CbpA) of Streptococcus pneumoniae to bind the third component of complement (C3) suggests possible interactions with opsonic C3 in the bloodstream or with C3 secreted by epithelial cells . The latter possibility was investigated by measuring C3 in supernatants of resting and cytokine-activated monolayers of type II pulmonary epithelial cells (A549 cells) . Expression of C3 on the epithelial cell surface was confirmed by immunofluorescence . Epithelially produced C3 bound to CbpA, as determined by Western blot test . cbpa(-) mutants and lysates therefrom failed to bind C3, were completely deficient in adhesion to a matrix in which C3 was the sole substrate, and demonstrated a moderate yet significant decrease in adhesion to type II pulmonary epithelial cells . These results confirm the interaction of the pneumococcal protein CbpA and its substrate, C3, in 2 in vitro models of adhesion.

J Infect Dis, 2000 Aug, 182(2), 490 - 6 Epub 2000 Jul 12.
Serotype distribution and antimicrobial resistance patterns of invasive isolates of Streptococcus pneumoniae: Alaska, 1991-1998; Rudolph KM et al.; From January 1991 through December 1998, a total of 1046 pneumococcal isolates were received from 23 laboratories participating in the statewide surveillance system . Of these, 1037 were recovered from normally sterile sites (blood and cerebrospinal and pleural fluid) and were available for serotyping and susceptibility testing . Ninety-two percent of these isolates were serotypes represented in the 23-valent pneumococcal polysaccharide vaccine . Serotypes in the 7-valent pneumococcal conjugate vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F) were recovered from 72% of Alaska Natives and 84% of non-Native children <5 years old with invasive disease . Statewide, 7.3% and 3.2% of isolates had intermediate and high levels of resistance to penicillin, respectively; 9.2% were resistant to erythromycin (minimal inhibitory concentration, >/=1 microg/mL) and 19% to trimethoprim/sulfamethoxazole (minimal inhibitory concentration, >/=4/76 microg/mL) . Twelve percent of invasive isolates were resistant to >/=2 classes of antibiotics; of these, serotype 6B accounted for 33%, and 63% were recovered from children <5 years old.

Harefuah, 1999 Jan 15, 136(2), 105 - 8, 176, 175
{Meningitis due to Streptococcus bovis type II}; Ben-Ami A et al.; Meningitis due to Streptococcus bovis is rare . Only 14 cases having been reported in the English literature . All patients (including the patient described) had an underlying disease or were treated by pharmacological agents that predisposed the patient to the infection . Most were treated by monotherapy with penicillin G (or amoxicillin) and recovered . We describe a 74-year-old woman who had splenectomy as treatment for hairy cell leukemia 6 months before hospitalization for meningitis and sepsis by S . bovis type II . She was successfully treated with intravenous amoxicillin . There was neither evidence of endocarditis nor carcinoma of the colon . Although the association between S . bovis meningitis and endocarditis or carcinoma of the gastrointestinal tract is not well established, we recommend a full work-up for GI malignancy and endocarditis in every patient with S . bovis meningitis.

Can J Microbiol, 2000 Jun, 46(6), 584 - 92
Mutational analysis of the C-terminal anchoring domains of Streptococcus mutans P1 antigen: role of the LPXTGX motif in P1 association with the cell wall; Lee SF et al.; The salivary agglutinin-interacting adhesin P1 of Streptococcus mutans is anchored to the cell wall via the carboxy (C) terminus, which contains a wall-associated domain, a conserved LPXTGX motif, a hydrophobic domain, and a charged tail . To further investigate the role of the C-terminal anchoring regions in cell wall sorting and anchoring, mutational analysis was performed on P1 in this study . Three truncated P1 mutants and seven site-directed mutants were generated by a polymerase chain reaction-based technique . The mutated P1 genes were returned to the P1-negative S . mutans SM3352 for expression and localization studies by ELISA and Western immunoblotting . The results showed that P1 mutants with deletion of the hydrophobic domain and charged tail, or deletion of the charged tail alone resulted in the secretion of P1 to the culture medium . Results from cellular fractionation experiments with the truncated mutants showed that P1 was not trapped in the membrane or cytoplasm . The site-directed mutants showed normal distribution of P1 to the cell surface as compared to the wild-type . However, when cell walls prepared from the site-directed mutants were boiled with SDS, P1 could be removed readily from the mutants with Thr residue in the LPNTGV motif, altered to either Ser (T1531S) or Phe (T1531F); the mutant with Thr and Gly residues altered to two Phe residues (TG1531-1532FF), and the LPNTGV-deleted mutant (LPNTGV-) . In contrast, the wild-type P1 and the other three site-directed P1 mutants (P1529V, N1530I, and G1532F) could not be removed by boiling SDS . When the cell wall P1s from the wild-type, mutants P1529V, N1530I, and G1532F were reacted with an antibody directed against the hydrophobic domain and charged tail, no reaction was detected . However, P1s from mutants T1531S, T1531F, TG1531-1532FF, and LPNTGV- were recognized by the antibody, indicating that the inability of these mutated P1s to firmly link to the cell wall was the result of failure in proteolytic cleavage of the hydrophobic domain and charged tail . In summary, the results suggest that the charged tail plays a decisive role in sorting P1 to the cell surface, while the LPXTGX motif determines the nature of P1-cell wall association . The Thr residue of the LPXTGX motif is required for enzymatic processing to link P1 to the cell wall, presumably via a covalent bond.

FEMS Microbiol Lett, 2000 Aug 1, 189(1), 89 - 92
Shifts in membrane fatty acid profiles associated with acid adaptation of Streptococcus mutans; Quivey RG Jr et al.; Cells of Streptococcus mutans UA159 physiologically adapted to acidification during growth at pH 5 in glucose-limited chemostat cultures were enriched in mono-unsaturated and longer chain fatty acids compared with unadapted cells grown under the same conditions but at pH 7 . Ratios of unsaturated to saturated fatty acids in the cells were, respectively, 1.2 and 0.3 . Cyclopropane fatty acids were not detected . Streptococcus sobrinus 6715, which is known to have minimal acid-adaptive capacity, showed only minimal change in membrane fatty acids.

FEMS Microbiol Lett, 2000 Jul 15, 188(2), 153 - 63
Purification and biochemical characterization of a basic superantigen (SPEX/SMEZ3) from Streptococcus pyogenes; Gerlach D et al.; A potent basic superantigen (designated streptococcal pyrogenic exotoxin X, SPEX/SMEZ3) was purified to homogeneity from culture supernatants of a Streptococcus pyogenes scarlatina strain of type 12 (genotype speA(-), speC(-)) and characterized . Sequence alignments revealed SPEX to be an allele of the streptococcal mitogens type Z (SMEZ) . The N-terminal amino acid sequence of SPEX was found with LEVDNNSLLR to be identical to the recently described acidic superantigen SMEZ . Although SPEX/SMEZ genes were present in all of the streptococcal strains tested, a toxin production could only be detected in a small number of strains . The produced toxin concentration in the culture supernatants of positive strains differed between 0 and 20 ng ml(-1) . The purified SPEX stimulated human T-lymphocytes with Vbeta8 specificity at extremely low concentrations (lower than 100 pg ml(-1)).

FEMS Microbiol Lett, 2000 Jul 15, 188(2), 125 - 8
The cyl genes of Streptococcus agalactiae are involved in the production of pigment; Spellerberg B et al.; The cyl genes of Streptococcus agalactiae are required for the production of hemolysin . Based on the observation that nonhemolytic S . agalactiae mutants do not produce pigment, a close genetic linkage between hemolysin and pigment has been postulated . To investigate this genetic linkage and to identify genes involved in the production of the S . agalactiae pigment, we screened mutant libraries for nonpigmented clones . Four distinct mutants were isolated with a nonpigmented and nonhemolytic phenotype . The mutations had occurred either in known cyl genes or in two open reading frames located immediately downstream . These novel genes are cotranscribed with the cyl gene cluster and were designated cylF and cylI . Our data indicate that identical genes participate in the production of S . agalactiae hemolysin and pigment.

J Bacteriol, 2000 Aug, 182(16), 4667 - 9
Dual functions of Streptococcus salivarius urease; Chen YY et al.; A urease-deficient derivative of Streptococcus salivarius 57.I was constructed by allelic exchange at the ureC locus . The wild-type strain was protected against acid killing through hydrolysis of physiologically relevant concentrations of urea, whereas the mutant was not . Also, S . salivarius could use urea as a source of nitrogen for growth exclusively through a urease-dependent pathway.

Harefuah, 1998 Nov 1, 135(9), 350 - 4, 407
{Nasopharyngeal colonization with Streptococcus pneumoniae in pediatric respiratory infections}; Srugo I et al.; During the winter of 1995, nasopharyngeal colonization of Streptococcus pneumoniae was evaluated in 204 children with respiratory infection and 107 normal control children . There was no difference in gender or mean age between the groups, and no difference in carrier rate between sick (24.5%) and normal (22%) children (p = 0.6) . Carrier rates were 19%, 32%, 31% and 17% at 6, 12, 24 and 48 months, respectively . Penicillin-resistant pneumococci (PRP) were found in 42% of sick and 16.6% of normal children, (p < 0.05) . Resistance to more than 2 antibiotics was found in 28% of sick and in 12.5% of normal children . PRP were found in 67% and 34% of sick children with and without prior antibiotic treatment (p < 0.05) . We conclude that there is no difference in the carrier rate of Streptococcus pneumoniae between sick and normal children . However, the high prevalence of PRP in children with respiratory infections is probably due to prior antibiotic treatment.

Acta Paediatr Taiwan, 1999 Jan-Feb, 40(1), 50 - 2
Isolation of Eikenella corrodens from polymicrobial hepatic abscess: report of one case; Chang PS et al.; Eikenella corrodens is a rare cause of hepatic abscess . We report a case of a hepatic abscess caused by (1) Bacteroides fragilis, (2) Streptococcus constellatus and (3) E . corrodens, which illustrates potential problems of antibiotic coverage due to the presence of Eikenella species . The infection followed an episode of acute gastroenteritis and the clinical course appeared indolent evolving over one week . Besides empirical antibiotics, initial percutaneous aspiration was performed and yielded pus which grew E . corrodens concomitantly with Streptococcus species . E . corrodens was sensitive to penicillin but resistant to clindamycin and metronidazole . But B . fragilis was resistant to penicillin . So the antibiotics were switched to amoxicillin/clavulanate . Unfortunately fever persisted and the abscess increased in size . Therefore echo-guided percutaneous drainage with pigtail catheter was installed . Fever subsided 5 days later . After 21 days treatment of antibiotics, the patient was discharged in good condition despite having some sterile fluid in the residual abscess cavity . Two months after discharge the follow-up echogram confirmed complete resolution of the residual abscess . This patient shows us the existence of E . corrodens in pediatric patients, especially when the hepatic abscess is very likely from the spread of an oral or abdominal infection.

J Am Vet Med Assoc, 2000 Jul 1, 217(1), 74 - 8
Treatment of supraspinous bursitis by use of debridement in standing horses: 10 cases (1968-1999); Hawkins JF et al.; OBJECTIVE: To evaluate efficacy of debridement for treatment of supraspinous bursitis in horses and to evaluate the outcome . DESIGN: Retrospective study . ANIMALS: 10 horses with clinical signs of supraspinous bursitis . PROCEDURE: Medical records were reviewed for signalment, anamnesis, results of physical and radiographic examination, microbial culture results of supraspinous bursa tissue or exudate, Brucella abortus titers, type of antimicrobial and anti-inflammatory therapies, surgical technique, complications of the surgical procedure, and findings on histologic examination of excised nuchal ligament and bursal tissue . Telephone follow-up with owners, trainers, or referring veterinarians was performed . RESULTS: The described surgical technique was effective in resolving drainage from the supraspinous bursal region in 5 of 6 horses available for long-term follow-up . The most common complication following surgery was the development of purulent wound drainage . Two horses required multiple surgeries to resolve clinical signs of supraspinous bursitis . The most common organism isolated from the supraspinous bursa was beta-hemolytic Streptococcus spp . All horses were discharged from the hospital and long-term follow-up was available for 6 horses . All 6 horses could be used for their intended use . CONCLUSIONS AND CLINICAL RELEVANCE: Debridement in standing horses is an effective method of resolving clinical signs of supraspinous bursitis.

J Am Vet Med Assoc, 2000 Jul 1, 217(1), 64 - 7, 30
Streptococcal toxic shock in a horse; Dolente BA et al.; A 14-year-old horse was admitted to the veterinary hospital for treatment of tachycardia and lethargy . Initial diagnoses were ventricular tachycardia and renal dysfunction . During hospitalization other findings included fever, renal failure, hepatic failure, hypotension, and intermittent ventricular arrhythmias . Bacteriologic culture of 2 blood samples collected during febrile crises 7 days apart yielded Streptococcus mitis . These culture results along with other clinical and physical examination findings fulfill the criteria for a diagnosis of streptococcal toxic shock syndrome, previously described for humans and dogs . To our knowledge this is the first reported instance of this disease in a horse.

Lab Invest, 2000 Jul, 80(7), 1095 - 100
Inhibition of monocyte chemotactic protein-1 synthesis by statins; Romano M et al.; The beneficial effects of statins on the reduction of cardiovascular events has been partly attributed to their anti-inflammatory properties . In the complex of the different pathogenetic events leading to atherosclerosis, recent data suggest a central role of monocyte chemotactic protein-1 (MCP-1), because mice knock-out for MCP-1 or its receptor CC-chemokine receptor 2 were considerably resistant to plaque formation . In this study we investigated the effect of different statins on in vitro and in vivo production of MCP-1 . Lovastatin and simvastatin caused a dose-dependent inhibition of MCP-1 production in peripheral blood mononuclear cells exposed to lipopolysaccharide or inactivated Streptococcus hemoliticus and in human endothelial cells exposed to interleukin-1beta . The addition of mevalonate overrode the inhibitory effect of statins indicating that mevalonate-derived products are important for chemokine production . The in vivo anti-inflammatory effect of statins was investigated using the mouse air-pouch model of local inflammation . Lovastatin and pravastatin were orally administered to mice according to a treatment schedule that significantly inhibited the hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity without affecting total blood cholesterol . At the dose of 10 mg/kg, lovastatin and pravastatin reduced by approximately 50% the lipopolysaccharide-induced leukocytes recruitment and the exudate MCP-1 production . In conclusion, statins, by inhibiting mevalonate-derived products, reduced both in vitro and in vivo the production of chemokines involved in leukocyte migration, and this effect is unrelated to their cholesterol-lowering action.

J Infect, 2000 May, 40(3), 285 - 6
Necrotizing proctitis caused by Streptococcus pyogenes; Barnham M et al.; We report the case of a 65-year-old patient with peritonitis, septicaemia and toxic shock syndrome in whom the primary focus of infection was acute purulent proctitis with necrosis . Streptococcus pyogenes serotype T28R28 was isolated from blood culture and peritoneal pus . The patient recovered after a prolonged period of intensive therapy and four abdominal operations including anterior resection of the rectum . We believe this to be the first clinical description of streptococcal necrotizing proctitis.

Clin Chest Med, 2000 Jun, 21(2), 301 - 13
The role of bacterial infections in asthma; Kraft M; In summary, bacterial organisms are clinically relevant contributors to asthma exacerbations, and have received much less attention than viruses in this process . Streptococcus pneumoniae, Hemophilus influenzae, and Moraxella catarrhalis have been linked to asthma exacerbations, particularly when sinusitis is present . Treatment therefore should be directed toward these organisms if a bacterial cause is suspected . The atypical bacteria--specifically, C . pneumoniae and M . pneumoniae--deserve special attention . Data suggest a link between these organisms and the exacerbation of asthma, as well as suggest that these organisms may be causative in asthma development . The existing data are not conclusive, but are suggestive enough to drive studies evaluating them as a possible mechanism in asthma pathogenesis . An animal model evaluating M . pneumoniae and C . pneumoniae would be ideal, but at present no model exists in which chronic infection with these organisms results in bronchial hyperresponsiveness . There is active work in this area, however . Alternative investigations include continued evaluation of these organisms by several modalities, including culture, serology, and PCR, along with evaluation of the host response . Many questions remain, but the ground is fertile for continued investigation.

Mayo Clin Proc, 2000 Jul, 75(7), 749 - 53
Pneumococcal vaccine in patients with absent or dysfunctional spleen; Kobel DE et al.; Four patients (3 long-term Hodgkin disease survivors and 1 recipient of an allogeneic bone marrow transplant) developed severe infections with Streptococcus pneumoniae after staging splenectomy or due to functional hyposplenism after total body irradiation and bone marrow transplantation . Current guidelines for prevention of infection recommend pneumococcal immunization for patients with Hodgkin disease treated with splenectomy and others with functional hyposplenism . Booster vaccination after 5 years is also advised . Hospital- and community-based vaccination initiatives may help identify at-risk patients.

Microb Pathog, 2000 Aug, 29(2), 127 - 34
The cps locus of Streptococcus suis serotype 2: genetic determinant for the synthesis of sialic acid; Smith HE et al.; The capsule of S . suis serotype 2 is composed of glucose, galatose, N-acetylglucosamine, rhamnose and sialic acid . Recently, we described a major part of the cps2 locus of S . suis serotype 2 . Based on sequence homology genes encoding potential glucosyl-, galactosyl-, N-acetylglucosaminyl- and rhamnosyltransferase activities could be identified . However, we did not find genes involved in the synthesis of sialic acid . Here, we describe the cloning and characterization of a remaining part of the cps2 locus . Based on the establish sequence 11 potential genes, designated orf2L, orf2M, orf2N, cps2O to cps2T, orf2U and orf2V were identified . A gene homologous to genes involved in the polymerization of the repeating oligosaccharide unit (cps2O) as well as genes involved in the synthesis of sialic acid (cps2P to cps2T) were identified . Moreover, hybridizing experiments showed that the genes involved in the sialic acid synthesis are present in S . suis serotype 1, 2, 14, 27 and 1/2 . The orf2M and orf2N regions showed similarity to proteins involved in the polysaccharide biosynthesis of other Gram-positive bacteria . However, these regions seemed to be truncated or were non-functional as the result of frame-shift or point mutations . At its 3;-end the cps2 locus contained two insertional elements (orf2U and orf2V), both of which seemed to be non-functional .

Microb Pathog, 2000 Aug, 29(2), 115 - 20
Characterization of bacterial orofacial infections using a new murine model; Kuriyama T et al.; We devised a new murine orofacial infection model using bacteria from odontogenic infection origins and characterized the experimental infections . In this model, bacteria were injected into the submandible of mice . Streptococcus constellatus and Peptostreptococcus micros produced a single abscess at the injection site and their abscess-forming and lethal abilities were low: the median abscess-forming dose (AF(50)) of S . constellatus and P . micros were 10(8.5-10.7)and 10(10.2-10.6)cfu/mouse, and their median lethal dose (LD(50)) were >11 and 10(10.6-11)cfu/mouse, respectively . Prevotella oralis and Fusobacterium nucleatum produced multiple abscesses and their abscess-forming and lethal abilities were strong: AF(50)of P . oralis and F . nucleatum were 10(6.0-6.4)and 10(7 . 0-8.7)cfu/mouse, and their LD(50)were 10(7.0-7.7)and 10(8.3-9 . 9)cfu/mouse, respectively . LD(50)of P . intermedia and P . gingivalis were 10(9.4->11)and 10(8.9-9.1)cfu/mouse, respectively . Prevotella intermedia and Porphyromonas gingivalis generated a necrotizing lesion, which progressed rapidly . We conclude that this murine model could reflect human orofacial odontogenic infections and is useful to investigate the pathogenicity of causative bacteria of such infections .

Microb Pathog, 2000 Aug, 29(2), 101 - 13
Environmental conditions modulate the expression of the sspA and sspB genes in Streptococcus gordonii; El-Sabaeny A et al.; The SspA and SspB surface proteins of Streptococcus gordonii are multifunctional adhesins encoded by tandemly arranged genes . The transcriptional regulation of the sspA and sspB genes was investigated by generating chromosomal promoter- cat gene fusions and measuring CAT enzyme activity . The sspA promoter was found to be three-fold more active than the sspB promoter . In addition, sspA transcriptional activity increased throughout growth, whereas sspB activity decreased in stationary phase . Promoter activity of both sspA and sspB was regulated in response to temperature, pH and osmolarity; however the two promoters showed a different pattern of regulation . Changes in promoter activity were reflected in levels of surface protein and in adherence of S . gordonii to Porphyromonas gingivalis, a phenotypic property dependent on Ssp proteins . The results show that S . gordonii strain DL1 differentially regulates sspA and sspB transcription in response to oral environmental cues, suggesting that the SspA and SspB polypeptides may have distinct functional roles in cell adherence to oral substrates .

Diagn Microbiol Infect Dis, 2000 Jul, 37(3), 187 - 93
In vitro study of the post-antibiotic effect and the bactericidal activity of Cefditoren and ten other oral antimicrobial agents against upper and lower respiratory tract pathogens; Dubois J et al.; The in vitro post-antibiotic effect (PAE) and batericidal activity of cefditoren was compared to that of cefixime, cefuroxime, loracarbef, cefaclor, amoxicillin, amoxicillin/clavulanate, clarithromycin, azithromycin, erythromycin, and ciprofloxacin against ATCC culture strains and clinical respiratory isolates . A PAE > 1 h was observed for cefditoren and generally for the macrolides against Streptococcus pneumoniae, beta-lactamase-negative Moraxella catarrhalis, and Streptococcus pyogenes, whereas the other beta-lactams showed mixed results . Cefditoren was the only beta-lactam showing significant bactericidal activity (>3 log reduction of viable cells) within 4 h against penicillin-resistant S . pneumoniae . Only cefditoren and ciprofloxacin showed significant bactericidal activity against beta-lactamase-negative (after 24 h) and beta-lactamase-positive strains of H . influenzae (after 12 h) . Against beta-lactamase-positive strains of M . catarrhalis, cefditoren was the only agent to show significant bactericidal activity at 6 h (versus cefuroxime and ciprofloxacin at 12 h).

J Biol Chem, 2000 Oct 6, 275(40), 30864 - 72
Biochemical and molecular analyses of the Streptococcus pneumoniae acyl carrier protein synthase, an enzyme essential for fatty acid biosynthesis; McAllister KA et al.; Acyl carrier protein synthase (AcpS) is an essential enzyme in the biosynthesis of fatty acids in all bacteria . AcpS catalyzes the transfer of 4'-phosphopantetheine from coenzyme A (CoA) to apo-ACP, thus converting apo-ACP to holo-ACP that serves as an acyl carrier for the biosynthesis of fatty acids and lipids . To further understand the physiological role of AcpS, we identified, cloned, and expressed the acpS and acpP genes of Streptococcus pneumoniae and purified both products to homogeneity . Both acpS and acpP form operons with the genes whose functions are required for other cellular metabolism . The acpS gene complements an Escherichia coli mutant defective in the production of AcpS and appears to be essential for the growth of S . pneumoniae . Gel filtration and cross-linking analyses establish that purified AcpS exists as a homotrimer . AcpS activity was significantly stimulated by apo-ACP at concentrations over 10 microm and slightly inhibited at concentrations of 5-10 microm . Double reciprocal analysis of initial velocities of AcpS at various concentrations of CoA or apo-ACP indicated a random or compulsory ordered bi bi type of reaction mechanism . Further analysis of the inhibition kinetics of the product (3',5'-ADP) suggested that it is competitive with respect to CoA but mixed (competitive and noncompetitive) with respect to apo-ACP . Finally, apo-ACP bound tightly to AcpS in the absence of CoA, but CoA failed to do so in the absence of apo-ACP . Together, these results suggest that AcpS may be allosterically regulated by apo-ACP and probably proceeds by an ordered reaction mechanism with the first formation of the AcpS-apo-ACP complex and the subsequent transfer of 4'-phosphopantetheine to the apo-ACP of the complex.

J Matern Fetal Med, 2000 Mar-Apr, 9(2), 126 - 30
Cost consequences of elimination of the routine group B streptococcus culture at a teaching hospital; Russell CS et al.; OBJECTIVE: To evaluate the cost consequence of the elimination of routine Group B streptococcus (GBS) cultures in pregnancy utilizing risk factor assessment management recommendations of the Center for Disease Control . METHODS: This retrospective study cohort population included all delivering patients from June 1, 1996, to May 31, 1997, managed by the Morbidity Mortality Weekly Report (MMWR) guidelines May 31, 1996, for GBS in pregnancy compared to the previous 29 months cohort from January 1, 1994, to May 31, 1996, managed with routine GBS cultures done at 35-37 weeks . RESULTS: Of the 7,681 culture management control cohort patients, there were four neonates with culture-positive GBS sepsis (1/1,900) . The cost for detection of a single positive culture in an affected neonate was $8,627 ($34,509/4) and there were 2,875 personnel hours expended . In contrast, of the 2,011 patients in the risk factor management cohort, there were two cases of neonatal GBS sepsis ($111,005) . The cost for detection of a positive culture in an affected neonate was $1,579 ($3,159/2) and there were 263 personnel hours expended in the risk factor management group . In spite of these significant laboratory savings, we noted a concurrent increase in the total cost in the newborn nursery for septic work-ups and treatment from $2.4 million to $3.1 million . CONCLUSION: Risk assessment management of GBS provided a savings of both money ($7,048/positive neonatal culture) and laboratory time (586 personnel hours/positive neonatal culture) . However, these savings were more than offset by cost increases occurring in the newborn nursery ($400,000), demonstrating the necessity of practice patterns to undergo concurrent evaluation to verify cost savings and prevent shifting of expenses.

Lancet, 2000 Jun 17, 355(9221), 2106 - 11
23-valent pneumococcal polysaccharide vaccine in HIV-1-infected Ugandan adults: double-blind, randomised and placebo controlled trial; French N et al.; BACKGROUND: Infection with Streptococcus pneumoniae is a frequent and serious problem for HIV-immunosuppressed adults . Vaccination is recommended in the USA and Europe, but there are no prospective data that show vaccine efficacy . METHODS: 1392 (937 female) HIV-1-infected adults in Entebbe, Uganda, were enrolled . 697 received 23-valent pneumococcal polysaccharide vaccine and 695 received placebo . The primary endpoint was first event invasive pneumococcal disease . Secondary endpoints included vaccine serogroup-specific invasive disease, all (probable and definite) pneumococcal events, all-cause pneumonia, and death . FINDINGS: First invasive events occurred in 25 individuals (24 bacteraemias, one pyomyositis), 15 in the vaccine arm and ten in the placebo arm (hazard ratio {HR} 1.47; 95% CI 0.7-3.3) . 22 isolates (88%) were of vaccine-specific serogroups with 15 events in the vaccine arm compared with seven in the placebo arm (HR 2.10; 0.9-5.2) . All pneumococcal events had a similar distribution (20 vs 14; HR 1.41; 0.7-2.8) though all-cause pneumonia was significantly more frequent in the vaccine arm (40 vs 21; HR 1.89; 1.1-3.2) . Mortality was unaffected by vaccination . INTERPRETATION: 23-valent pneumococcal polysaccharide vaccination is ineffective in HIV-1-infected Ugandan adults and probably has little, or no, public health value elsewhere in sub-Saharan Africa . Increased rates of pneumococcal disease in vaccine recipients may necessitate a reappraisal of this intervention in other settings.

Pac Symp Biocomput . 2000;:155-67.
Pinpointing the putative heparin/sialic acid-binding residues in the 'sushi' domain 7 of factor H: a molecular modeling study; Ranganathan S et al.; Factor H, a secretory glycoprotein comprising 20 short consensus repeat (SCR) or 'sushi' domains of about 60 amino acids each, is a regulator of the complement system . The complement-regulatory functions of factor H are targeted by its binding to polyanions such as heparin/sialic acid, involving SCRs 7 and 20 . Recently, the SCR 7 heparin-binding site was shown to be co-localized with the Streptococcus Group A M protein binding site on factor H (T.K . Blackmore et al., Infect . Immun . 66, 1427 (1998)) . Using sequence analysis of all heparin-binding domains of factor H and its closest homologues, molecular modeling of SCRs 6 and 7, and surface electrostatic potential studies, the residues implicated in heparin/sialic acid binding to SCR 7 have been localized to four regions of sequence space containing stretches of basic as well as histidine residues . The heparin-binding site is spatially compact and lies near the interface between SCRs 6 and 7, with residues in the interdomain linker playing a significant role.

Z Kardiol, 2000 May, 89(5), 464 - 8
{A case report: suppurative pericardial effusion}; Zacharowski K et al.; We present the case of a 67 year old woman who was resuscitated due to cardiac tamponade . Examination of the pus fluid showed a bacterial infection with streptococcus milleri . Four days before resuscitation the patient experienced weakness, dyspnoea, increased temperature (39 degrees C), swelling of the neck, and pain on swallowing . Using computed tomography, examination revealed an infection extending from the right tonsil to the mediastinum and into the pericardium . After surgery to remove the retropharyngeal abscess, the patient healed well . Therefore, on presentation of a cardiac tamponade, possible hematogenous or lymphogenous causes or per continuitatem infections should always be considered . In this case the germs in the fluid and the typical patient history indicated an oropharyngeal reason.

Infect Immun, 2000 Aug, 68(8), 4818 - 21
Role of monocytes in experimental Staphylococcus aureus endocarditis; Veltrop MH et al.; In the pathogenesis of bacterial endocarditis (BE), the clotting system plays a cardinal role in the formation and maintenance of the endocardial vegetations . The extrinsic pathway is involved in the activation of the coagulation pathway with tissue factor (TF) as the key protein . Staphylococcus aureus is a frequently isolated bacterium from patients with BE . We therefore investigated whether S . aureus can induce TF activity (TFA) on fibrin-adherent monocytes, used as an in vitro model of BE . We also assessed in vivo in rabbits with catheter induced vegetations, the effect of S . aureus infection on vegetational TFA . In vitro experiments showed that adherent S . aureus induced TFA on fibrin-adherent monocytes which was optimal at a bacterium/monocyte ratio of 1 to 1 . Monocyte damage occurred when this ratio exceeded 4 to 1 (visually) or 6 to 1 (propidium iodide influx) Consequently, TFA decreased . In vivo S . aureus led to very high bacterial numbers in the vegetations and a significant increase of their weight . However, TFA of infected vegetations was the same as of sterile ones . This may be due to the high bacteria to monocyte ratio as well as bacterium-induced monocyte damage . Teicoplanin treatment of infected rabbits reduced bacterial numbers in the blood and in the vegetations . Two-day treatment resulted in an increase of vegetational TFA, but after four-day treatment vegetational TFA dropped, most probably due to a suboptimal bacterium/monocyte ratio . S . aureus endocarditis in etoposide (Vepesid)-treated rabbits, leading to a selective monocytopenia, caused a rapid death of the animals . In these rabbits no vegetations were found at all . We conclude that, like Streptococcus sanguis and Staphylococcus epidermidis, S . aureus is able to induce TFA in fibrin-adherent blood monocytes . In addition, monocytes have a protective effect during the course of S . aureus endocarditis.

Infect Immun, 2000 Aug, 68(8), 4792 - 4
Streptococcus pneumoniae induces secretion of vascular endothelial growth factor by human neutrophils; van Der Flier M et al.; Infection by pneumococci causes an acute inflammatory response associated with neutrophil influx, increased vascular permeability, and edema . Vascular endothelial growth factor (VEGF) is one of the most potent regulators of endothelial permeability . In vitro stimulation of neutrophils showed that pneumococci and purified pneumococcal cell wall induce VEGF secretion, independent of the presence of pneumolysin or polysaccharide capsule . The results of this study indicate VEGF is secreted in pneumococcal disease, suggesting a role as a mediator of increased vascular permeability.

Infect Immun, 2000 Aug, 68(8), 4786 - 8
Nonimmune interaction of the SfbI protein of Streptococcus pyogenes with the immunoglobulin G F(ab')(2) fragment; Medina E et al.; Fibronectin-binding protein I (SfbI) of Streptococcus pyogenes binds to mouse immunoglobulin G (IgG) but not to IgA or IgM in a nonimmune fashion . The fibronectin-binding domains of SfbI were responsible for this activity, which was targeted to the IgG F(ab')(2) fragment . SfbI also binds to B cells but not to CD4(+) or CD8(+) lymphocytes.

Infect Immun, 2000 Aug, 68(8), 4773 - 7
Characterization of the Streptococcus mutans pyruvate formate-lyase (PFL)-activating enzyme gene by complementary reconstitution of the In vitro PFL-reactivating system; Yamamoto Y et al.; The act gene was identified and an act mutant as well as the pfl mutant was constructed in Streptococcus mutans . Pyruvate formate-lyase (PFL) activity was regenerated with the mixture of the respective cell extracts from these mutants by complementary reconstitution of the in vitro reactivating system . The S . mutans act gene encoded the sole enzyme able to activate the PFL protein in this organism.

Infect Immun, 2000 Aug, 68(8), 4681 - 7
Toll-like receptor 4-deficient mice have reduced bone destruction following mixed anaerobic infection; Hou L et al.; C3H/HeJ mice have an impaired ability to respond to lipopolysaccharide (LPS) due to a mutation in the gene that encodes Toll-like receptor 4 (TLR4) . The effect of TLR4 deficiency on host responses to endodontic infections is unknown . In the present study, we compared periapical bone destruction, sepsis, and inflammatory cytokine production in LPS-hyporesponsive C3H/HeJ and wild-type control C3H/HeOuJ mice . The mandibular first molars of both strains were subjected to pulpal exposure and infection with a mixture of four anaerobic pathogens, Prevotella intermedia, Fusobacterium nucleatum, Streptococcus intermedius, and Peptostreptococcus micros . At sacrifice on day 21, TLR4-deficient C3H/HeJ mice had significantly reduced periapical bone destruction compared to wild-type C3H/HeOuJ mice (P < 0.001) . The decreased bone destruction in C3H/HeJ correlated with reduced expression of the bone resorptive cytokines interleukin 1alpha (IL-1alpha) (P < 0.01) and IL-1beta (P < 0.05) as well as the proinflammatory cytokine IL-12 (P < 0.05) . No significant differences were seen in the levels of gamma interferon, tumor necrosis factor alpha (TNF-alpha), or IL-10 between the two strains . The expression of IL-1alpha, IL-1beta, TNF-alpha, IL-10, and IL-12 were all significantly reduced in vitro in macrophages from both TLR4-deficient C3H/HeJ and C57BL/10ScNCr strains, compared to wild-type controls . Notably, the responses of TLR4-deficient macrophages to both gram-positive and gram-negative bacteria were similarly reduced . Neither C3H/HeJ nor C3H/HeOuJ mice exhibited orofacial abscess development or infection dissemination as determined by splenomegaly or cachexia . We conclude that intact TLR function mediates increased proinflammatory responses and bone destruction in response to mixed anaerobic infections.

Infect Immun, 2000 Aug, 68(8), 4604 - 10
Differential protein expression in phenotypic variants of Streptococcus pneumoniae; Overweg K et al.; Streptococcus pneumoniae undergoes spontaneous phase variation resulting in opaque and transparent colony forms . Differences in colony opacity correlate with differences in virulence: the transparent variants are more capable of colonizing the nasopharynx, whereas the opaque variants show increased virulence during systemic infections . To gain insight into the pathogenesis of pneumococcal disease at the molecular level, protein expression patterns of the phenotypic variants of two pneumococcal strains were compared by high-resolution two-dimensional protein electrophoresis . In comparison with transparent variants, the opaque variants reduced the expression of two proteins and overexpressed one protein . The proteins were identified by mass spectrometric analysis . The protein overexpressed in the opaque phenotype revealed significant homology to elongation factor Ts of Helicobacter pylori . One of the two proteins that were underexpressed in the opaque variants revealed significant homology to the proteinase maturation protein PrtM of Lactocobacillus paracasei, a member of the family of peptidyl-prolyl cis/trans isomerases . A consensus lipoprotein signal sequence suggests that the putative proteinase maturation protein A, designated PpmA, is located at the surface of the pneumococcus and may play a role in the maturation of surface or secreted proteins . The second underexpressed protein was identified as pyruvate oxidase, SpxB . The lower SpxB expression in opaque variants most probably explains the reduced production of hydrogen peroxide, a reaction product of SpxB, in this variant . Since a spxB-defective pneumococcal mutant has decreased ability to colonize the nasopharynx (B . Spellerberg, D . R . Cundell, J . Sandros, B . J . Pearce, I . Idanpaan-Heikkila, C . Rosenow, and H . R . Masure, 1996 . Mol . Microbiol . 19:803-813, 1996), our data suggest that SpxB plays an important role in enhancing the ability of transparent variants to efficiently colonize the nasopharynx.

Antimicrob Agents Chemother, 2000 Aug, 44(8), 2193 - 6
Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae isolates from pediatric patients in Singapore; Soh SW et al.; One hundred eighty Streptococcus pneumoniae strains isolated from children at a pediatric hospital in Singapore from 1997 to 1999 were serotyped and their antimicrobial susceptibility patterns were determined . Sixty-three percent of the isolates were resistant to penicillin . Significantly large numbers of the strains investigated were resistant to trimethoprim-sulfamethoxazole (87.8%), tetracycline (71.7%), erythromycin (67.8%), and chloramphenicol (40%) . Penicillin and multidrug resistance was mostly associated with the frequently isolated S . pneumoniae isolates of serotypes (serotypes 19F, 23F, 6B, and 14) . Isolates of serotype 19F, the serotype most commonly encountered in Singapore (41.1%), had the highest prevalence of penicillin (78.4%) and multidrug resistance (94.6%) . Most of the invasive S . pneumoniae isolates (8 of 17; 47 . 1%) were of serotype 14.

Antimicrob Agents Chemother, 2000 Aug, 44(8), 2118 - 25
Mutations in 23S rRNA and ribosomal protein L4 account for resistance in pneumococcal strains selected in vitro by macrolide passage; Tait-Kamradt A et al.; The mechanisms responsible for macrolide resistance in Streptococcus pneumoniae mutants, selected from susceptible strains by serial passage in azithromycin, were investigated . These mutants were resistant to 14- and 15-membered macrolides, but resistance could not be explained by any clinically relevant resistance determinant {mef(A), erm(A), erm(B), erm(C), erm(TR), msr(A), mph(A), mph(B), mph(C), ere(A), ere(B)} . An investigation into the sequences of 23S rRNAs in the mutant and parental strains revealed individual changes of C2611A, C2611G, A2058G, and A2059G (Escherichia coli numbering) in four mutants . Mutations at these residues in domain V of 23S rRNA have been noted to confer erythromycin resistance in other species . Not all four 23S rRNA alleles have to contain the mutation to confer resistance . Some of the mutations also confer coresistance to streptogramin B (C2611A, C2611G, and A2058G), 16-membered macrolides (all changes), and clindamycin (A2058G and A2059G) . Interestingly, none of these mutations confer high-level resistance to telithromycin (HMR-3647) . Further, two of the mutants which had no changes in their 23S rRNA sequences had changes in a highly conserved stretch of amino acids ((63)KPWRQKGTGRAR(74)) in ribosomal protein L4 . One mutant contained a single amino acid change (G69C), while the other mutant had a 6-base insert, resulting in two amino acids (S and Q) being inserted between amino acids Q67 and K68 . To our knowledge, this is the first description of mutations in 23S rRNA genes or ribosomal proteins in macrolide-resistant S . pneumoniae strains.

Perit Dial Int, 2000 May-Jun, 20(3), 354 - 8
Peritonitis prevention in CAPD: to mask or not?
Figueiredo AE, Poli de Figueiredo CE, d'Avila DO.
OBJECTIVE: To assess the efficacy of wearing a face mask to prevent peritonitis during continuous ambulatory peritoneal dialysis (CAPD) bag exchange . SETTING: Renal unit at a university hospital . PATIENTS: Two groups of patients on CAPD were compared: those performing bag exchange with (n = 24) and those without a face mask (n = 40) . OUTCOMES: Occurrence of first episode of peritonitis and total number of episodes . RESULTS: No difference was found between groups with respect to probability of developing the first episode of peritonitis (p = 0.757) . Patients holding university degrees had evidence of protection, with borderline significance {relative risk (RR) 0.52; confidence interval (CI) 95%, 0.23 -1.18; p= 0.109} . Cox's proportional hazard regression analysis also demonstrated a significant protective factor for patients with university level education (RR 0.42; Cl 95%, 0.18 - 0.98; p = 0.04) . Incidence of peritonitis was not significantly different between groups: with-mask group had 1.0 episode/year, and without-mask group had 0.94 episodes/year . Staphylococcus epidermidis was the most commonly identified agent . Staphylococcus aureus was found more frequently in the with-mask group (p = 0.003) . Peritonitis due to Streptococcus viridans and Enterococci were detected only in the without-mask group . CONCLUSION: The current study suggests that routine use of face masks during CAPD bag exchanges may be unnecessary and could be discontinued.

Adv Exp Med Biol, 2000, 479, 61 - 71
Initial steps in Streptococcus pneumoniae interaction with and pathogenicity to the host; Shani-Sekler M et al.; Streptococcus pneumoniae (Pnc) is one of the leading pathogens in the world . Attachment to respiratory mucosal and lung surfaces is presumed to be involved in carriage, in disease and in the interaction with macrophages initiating innate immune responses . We hypothesized that bacterial adhesins mediate Pnc adhesion and host cell invasiveness . Initial studies have focused on the purification of cell wall and membrane proteins using fetuin affinity chromatography, SDS PAGE and western blot analysis probed with pooled healthy human sera . Using a Pnc clinical isolate, and a gpt mutant we have detected 10-lectin proteins isolated from the cell wall and adherent to the affinity column and 15 lectins isolated from membrane extracts . The fetuin-captured lectins agglutinated rabbit erythrocytes . 15 proteins in the cell wall and 18 proteins in the membrane that failed to bind to the fetuin column did not agglutinate rabbit erythrocytes . Further purification of the cell wall and membrane fetuin-separated fractions was achieved via anion exchange FPLC, was verified by SDS PAGE . These proteins maintained their agglutinating activity, and were subsequently tested for their ability to interfere with Pnc adhesion and invasion of epithelial cells in culture . Additional biochemical, immunological and molecular techniques are being used in attempt to identify relevant proteins.

Am J Vet Res, 2000 Jul, 61(7), 779 - 83
Bacterial contamination of suction tips used during surgical procedures performed on dogs and cats; Sturgeon C et al.; OBJECTIVE: To determine prevalence of bacterial contamination of surgical suction tips . SAMPLE POPULATION: Surgical tips used during 44 surgical procedures performed on 42 dogs and 2 cats . PROCEDURE: Surgical procedures were classified into 1 of 3 categories according to degree of bacterial contamination of the surgical site (clean, clean-contaminated, contaminated) . Two sets of suction apparatuses were used for test and control suction tips . Test tips were used normally to suction blood and fluid, whereas control tips were placed on the surgical drapes but not in the surgical wound . Suction tips were collected aseptically and placed into thioglycolate broth tubes for qualitative aerobic and anaerobic bacterial culture at the end of each procedure . RESULTS: Test and control suction tips were contaminated with bacteria during 30 of 44 (68%) procedures . Staphylococcus spp were the predominant bacteria in tips used during clean and clean-contaminated surgeries . When surgery was performed on clean-contaminated or contaminated wounds, prevalence of isolation of other bacteria such as Pseudomonas spp, Streptococcus spp, and Escherichia coli from both test and control suction tips was higher than for clean wounds . Mean time of procedures during which both test and control suction tips became contaminated was not significantly different from time of procedures during which neither tip became contaminated . CONCLUSION AND CLINICAL RELEVANCE: Surgical suction tips often become contaminated during standard veterinary surgical procedures . The risk of wound infection after surgery may be influenced by bacterial contamination of surgical suction tips.

Oral Microbiol Immunol, 1999 Dec, 14(6), 348 - 51
Proteolysis and utilization of albumin by enrichment cultures of subgingival microbiota; Wei GX et al.; Subgingival dental plaque consists mainly of microorganisms that derive their energy from amino acid fermentation . Their nutrient requirements are met by the subgingival proteolytic system, which includes proteases from microorganism and inflammatory cells, and substrate proteins from sulcus exudate, including albumin . To determine the selective effect of individual proteins on microbiota, we used albumin as the main substrate for growth . Eight subgingval plaque samples from untreated periodontal pockets of patients with adult periodontitis were inoculated in peptone yeast medium with bovine albumin (9 g/l) . After three subculture steps, cell yields of the enrichment cultures at the medium with 0, 1.25, 2.5, 5, 10, and 20 g/l albumin were determined . Proteolytic activity (U/absorbance at 550 nm) of the enrichment cultures and different isolates derived from the cultures was estimated by the degradation of resorufin-labeled casein . It was observed that the yield of the mixed culture was albumin limited, and the proteolytic activities of the cultures in albumin broth were higher than in control (peptone broth) . Among the isolates from the enrichment cultures, Peptostreptococcus micros, Prevotella melaninogenica, Prevotella buccae and Prevotella bivia demonstrated proteolysis . The frequent occurrence of Streptococcus gordonii and Streptococcus anginosus in the albumin cultures is explained by their ability to utilize arginine as an energy source for growth . Albumin in the medium was partly degraded by pure cultures but completely consumed in enrichment cultures, indicating synergy of bacterial proteinases . It is concluded that the subgingival microbiota possesses proteolytic activity and may use albumin as a substrate for their growth . Enrichment cultures on albumin may serve as a relatively simple in vitro model to evaluate the effects of proteinase inhibitors.

J Bacteriol, 2000 Aug, 182(15), 4146 - 52
Two active forms of UDP-N-acetylglucosamine enolpyruvyl transferase in gram-positive bacteria; Du W et al.; Gene sequences encoding the enzymes UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) from many bacterial sources were analyzed . It was shown that whereas gram-negative bacteria have only one murA gene, gram-positive bacteria have two distinct genes encoding these enzymes which have possibly arisen from gene duplication . The two murA genes of the gram-positive organism Streptococcus pneumoniae were studied further . Each of the murA genes was individually inactivated by allelic replacement . In each case, the organism was viable despite losing one of its murA genes . However, when attempts were made to construct a double-deletion strain, no mutants were obtained . This indicates that both genes encode active enzymes that can substitute for each other, but that the presence of a MurA function is essential to the organism . The two genes were further cloned and overexpressed, and the enzymes they encode were purified . Both enzymes catalyzed the transfer of enolpyruvate from phosphoenolpyruvate to UDP-N-acetylglucosamine, confirming they are both active UDP-N-acetylglucosamine enolpyruvyl transferases . The catalytic parameters of the two enzymes were similar, and they were both inhibited by the antibiotic fosfomycin.

Comp Med, 2000 Jun, 50(3), 292 - 5
Effect of anesthetics on pathogenesis of experimentally induced murine pneumococcal pneumonia; Rubins JB et al.; BACKGROUND AND PURPOSE: To define the effects of three commonly used anesthetic agents--sodium pentobarbital given intraperitoneally, and inhaled halothane and methoxyflurane--on the pathogenesis of pneumococcal pneumonia and bacteremia in an experimental murine model . METHODS: Swiss outbred mice were anesthetized with either sodium pentobarbital, halothane, or methoxyflurane before intranasal infection with Streptococcus pneumonia . At defined times after infection, bacterial numbers in lungs and blood, markers of acute lung injury, and lung cytokine levels were compared . RESULTS: Mice anesthetized with inhaled halothane or methoxyflurane prior to intranasal inoculation with type-2 Streptococcus pneumoniae developed pneumonia and bacteremia distinctly different from that in mice anesthetized by intraperitoneal (IP) administration of sodium pentobarbital . Mice having brief exposure to inhaled halothane or methoxyflurane had significantly greater numbers of bacteria in lungs and blood 48 hours after inoculation, compared with mice anesthetized by IP administration of pentobarbital . Also, mice inhaling halothane had significantly decreased activities of pro-inflammatory cytokines interleukin 6 and tumor necrosis factor-alpha in lung homogenates at 24 hours after inoculation, compared with those given pentobarbital IP . CONCLUSION: Effects of anesthesia on murine models of pneumonia should be considered in the design and interpretation of studies of pneumococcal pathogenesis.

N Z Med J, 2000 May 12, 113(1109), 161 - 4
Severe community acquired pneumonia: a one-year analysis in a tertiary referral intensive care unit; Gowardman J et al.; AIMS: To define outcomes, characteristics, microbiology and salient prognostic factors of patients admitted to our intensive care unit (ICU) with severe community acquired pneumonia, over a one year period . METHODS: All adult patients with severe community acquired pneumonia admitted between July 1997 and July 1998 were studied . Data were extracted by retrospective chart review . Variables assessed included underlying conditions and baseline physical parameters . Evolutionary variables eg, septic shock and laboratory data including microbiology and arterial blood gas determinants were also assessed . Prognostic factors were determined by comparison of the above variables between survivors and non-survivors . The prognostic value of the British Thoracic Society discriminant 'rule one' was assessed . Results . 32 patients were assessed . ICU mortality was 31% . 84% of patients had co-morbidity . The average age was 58.5 (SD 17.4) years and the average APACHE 11 score was 20.37 (SD 9.12) . A microbiological diagnosis was made in 40% . Mortality was not increased in those in whom a bacterial diagnosis was not made . Commonest pathogens isolated were Streptococcus pneumoniae (46%), gram negative organisms (29%) and Staphylococcus aureus (23%) . Prognostic factors on and during ICU admission were the need for mechanical ventilation (p=0.0003), septic shock (p=0.02), inotrope requirement (p=0.003), low serum albumin (p=0.041), base deficit (p=0.04), INR (p=0.02) and inspired oxygen concentration (p=0.003) . On initial admission to hospital the presence of bilateral pneumonia was the only variable correlated with outcome (p=0.01) . The British Thoracic Society 'rule one' did not correlate with death either on admission to hospital or ICU . CONCLUSIONS: Severe community acquired pneumonia carries a high mortality despite ICU management . Bacterial diagnostic rate was low but made no difference to mortality . Streptococcus pneumoniae was the commonest causative pathogen . The development of septic shock, requirement for mechanical ventilation and bilateral disease are important adverse prognostic indicators.

Int J Sports Med, 2000 May, 21 Suppl 1, S4 - 9
Cytokines in aging and exercise; Pedersen BK et al.; Aging is associated with increased inflammatory activity . Increased plasma levels of tumour necrosis factor (TNF)-alpha were found in centenarians aged 100 years and in individuals aged 80-81 years when compared to a young control group . Plasma levels of TNF-alpha were linearly correlated to plasma levels of interleukin (IL)-6, TNF-receptors and C-reactive protein . High levels of TNF-alpha were directly related to dementia and to a low blood pressure ankle-arm index, indicating generalized atherosclerosis . In hospitalized patients with Streptococcus pneumonia infection, aging was associated with prolonged inflammatory activity . Similar results were found using an in vivo endotoxin challenge model in old versus young humans . Strenuous exercise induces increased levels in a number of proinflammatory and anti-inflammatory cytokines, naturally occurring cytokine inhibitors and chemokines . Thus, increased plasma levels of TNF-alpha, IL-1, IL-6, IL-1 receptor antagonist (IL-Ira), TNF-receptors (TNF-R), IL-10, IL-8 and macrophage inflammatory protein (MIP)-1 are found after strenuous exercise . The cytokine response to strenuous exercise has similarities to the cytokine response to trauma and sepsis . Therefore, in future studies, exercise is suggested as an ethically applicable model to use in studies on mechanisms underlying the age-associated altered cytokine response.

Protein Sci, 2000 Jun, 9(6), 1210 - 6
Overall rotational diffusion and internal mobility in domain II of protein G from Streptococcus determined from 15N relaxation data; Tillett ML et al.; The backbone dynamics and overall tumbling of protein G have been investigated using 15N relaxation . Comparison of measured R2/R1 relaxation rate ratios with known three-dimensional coordinates of the protein show that the rotational diffusion tensor is significantly asymmetric, exhibiting a prolate axial symmetry . Extensive Monte Carlo simulations have been used to estimate the uncertainty due to experimental error in the relaxation rates to be D(parallel)/D(perpendicular) = 1.68 +/- 0.08, while the dispersion in the NMR ensemble leads to a variation of D(parallel)/D(perpendicular) = 1.65 +/- 0.03 . Incorporation of this tensorial description into a Lipari-Szabo type analysis of internal motion has allowed us to accurately describe the local dynamics of the molecule . This analysis differs from an earlier study where the overall rotational diffusion was described by a spherical top . In this previous analysis, exchange parameters were fitted to many of the residues in the alpha helix . This was interpreted as reflecting a small motion of the alpha helix with respect to the beta sheet . We propose that the differential relaxation properties of this helix compared to the beta sheet are due to the near-orthogonality of the NH vectors in the two structural motifs with respect to the unique axis of the diffusion tensor . Our analysis shows that when anisotropic rotational diffusion is taken into account NH vectors in these structural motifs appear to be equally rigid . This study underlines the importance of a correct description of the rotational diffusion tensor if internal motion is to be accurately investigated.

Acta Med Port, 1999 Dec, 12(12), 381 - 6
{Infective endocarditis}; Proenca R et al.; Two different series of patients with Infectious Endocarditis (IE), hospitalized in the same ward of Curry Cabral Hospital in Lisbon, are presented and compared . The two series were separated by a ten-year period--the first included patients observed from 1970 to 1976 and the second from 1988 to 1998 . In the first series (20 patients), IE occurred mainly in patients with previous cardiac valvular lesion, the course was subacute and Streptococcus viridans was the predominant agent . In the last series (65 patients), most of the patients were young and had no previous valvular lesions . Right side endocarditis predominated and the course was acute . Most of patients were drug addicts and had HIV infection . Staphylococcus aureus was the predominant agent . The ages of the two series were significantly different (p < 0.005) . The diagnostic value of transthoracic and transesophageal echocardiography is stressed . The details of the evolution of patients with HIV infection are presented according to the values of CD4+ lymphocyte counts . The relatively good prognosis of IE in drug addicts with antibiotic treatment, even with HIV infection, is emphasized.

Microbiol Immunol, 2000, 44(5), 385 - 8
Helicobacter pylori may have only a transient presence in the oral cavity and on the surface of oral cancer; Okuda K et al.; We used the reverse transcription polymerase chain reaction (RT-PCR) and culture methods to study the presence of Helicobacter pylori in the gastric and oral samples from a total of 116 gastritis and peptic ulcer patients, including 58 with oral cancer . Detection rates of H . pylori were 46.6% in stomach samples and 12.1% in oral swab samples . All of the oral cancer surface swab samples were positive for H . pylori, as were their gastric samples suggesting that oral H . pylori derived from the stomach . The culture supernatants of Streptococcus mutans and Prevotella intermedia inhibited the growth of the H . pylori strain and caused the formation of the coccal form . In cases where H . pylori was detected in the oral cavity samples, including the oral cancer surface samples, it was believed that this species had colonized the stomach and were present in the oral cavity only as a transient organism.

Rev Cubana Med Trop, 1999 Sep-Dec, 51(3), 160 - 5
{Production and partial purification of the main hemolysin (pneumolysin) of Streptococcus pneumoniae}; Torano Peraza GT et al.; The capacity of 36 Cuban strains of Streptococcus pneumoniae to produce pneumolysin was studied, and 94.4% of them were determined to be producers of that enzyme . One of the best producers was cultured at a great scale and the pneumolysin found in the supernatan was partially purified through an ion-exchange chromatography in mono-Q column . This method made it possible to recover the enzyme whose purity level increased by 4.39 with 100% output.

Rev Cubana Med Trop, 1999 Sep-Dec, 51(3), 149 - 51
{Mouth colonization by Streptococcus pyogenes in patients with impetigo}; Ronconi MC et al.; The faucial carrying of Streptococcus pyogenes in patients presenting impetigo was determined as a risk factor for non-suppurative complications (acute glomerulonephritis) . The fauces cultures of these patients revealed a S . pyogenes colonization of 65% and all the isolates were penicillin-sensitive . It was concluded that the high percent of faucial colonization made a systemic antimicrobial treatment necessary.

Rev Cubana Med Trop, 1999 May-Aug, 51(2), 125 - 7
{Report of a case of purulent rhinitis caused by Streptococcus pneumoniae in a patient with HIV/AIDS}; Cabrera Cantelar N et al.; This paper reports a case of acute purulent rhinitis caused by Streptococcus pneumoniae in a HIV/AIDS patient seen at the Hospitalization Center of "Pedro Kouri" Tropical Medicine Institute . The clinical findings were fever, severe purulent rhinorrea and affected general condition . Streptococcus pneumoniae was isolated with standard and advanced diagnosis techniques . Antimicrobial sensitivity test revealed that it was sensitive to cefaloridien, ampicillin, penicillin G and oxacillin . The patient was treated with a dose of 2 g of ampicillin daily for 10 days . The clinical picture of the patient improved and there was a total remission of the symptoms.

Scand J Immunol, 2000 Jul, 52(1), 39 - 45
Activation of murine peritoneal macrophages by Streptococcus pneumoniae type II capsular polysaccharide: involvement of CD14-dependent pathway; Um SH et al.; In this study we examined the ability of capsular polysaccharide type 2 (PS) from Streptococcus pnemoniae to induce secretory and cellular responses in peritoneal macrophages . Tumour cytotoxicity induced by preincubation with PS was demonstrated to be concentration-dependent . PS-induced tumouricidal activity was partially abrogated by anti-tumour necrosis factor (TNF)-alpha and inhibitor of nitric oxide, whereas anti-interferon (IFN)-alpha/beta antibody and the scavengers of reactive oxygen intermediates had no effect . In addition, supernatants from macrophages treated with PS contained TNF-alpha, and their iNOS-enzymatic activity was significantly increased . Thus, the tumouricidal activity induced by PS appeared to be mediated by the production of TNF-alpha and nitrite . Treatment of macrophages with PS increased the expression of CD14, the receptor for lipolysaccharide (LPS)/LPS-binding protein . Moreover, blocking antibody to CD14 abrogated partially TNF-alpha and nitrite induction by PS, suggesting that the PS-induced CD14 upregulation was correlated with secretion of TNF-alpha and nitrite . Taken together, these results demonstrate that PS may induce macrophage-secretory and cellular activities, in part, possibly via CD14-dependent pathway.

Eur Respir J, 2000 Jun, 15(6), 1079 - 86
Neutrophils released from the bone marrow by granulocyte colony-stimulating factor sequester in lung microvessels but are slow to migrate; van Eeden SF et al.; Inflammatory mediators such as granulocyte colony-stimulating factor (G-CSF) release polymorphonuclear leukocytes (PMNL) from the bone marrow . This growth factor is used to promote the host response to infection but its effect on the behaviour of leukocytes at the inflammatory site is unclear . This study examined the sequestration and migration of PMNL released from the bone marrow by G-CSF in a model of streptococcal pneumonia . Eight hours following the administration of either human G-CSF (n=6) or saline (n=3) in rabbits, a focal Streptococcus pneumoniae pneumonia was induced and the animals were followed for 2 h . The thymidine analogue 5'-bromo-2'-deoxyuridine (BrdU) was used to label PMNL (PMNL(BrdU)) in the marrow and as a marker of PMNL newly released by the bone marrow . The PMNL(BrdU) in the lung and blood were identified using immunohistochemistry . G-CSF pretreatment elevated the circulating PMNL (3.6+/-0.4 (mean+/-SEM) to 8.3+/-1X10(9) x L(-1), p<0.05) and PMNL(BrdU) (5.4+/-2.1 to 12.5+/-3.1%, p<0.05) counts at 8 h with little further increase caused by the subsequent 2 h pneumonia . These counts did not change in the control group . Morphometric studies of the lung showed that the total number of PMNL sequestered in lung capillaries were increased in the G-CSF group and the percentage of the these PMNL that were BrdU-labelled, was higher than in circulating blood (p<0.05) . In the G-CSF group, only 11.2+/-2.6% of the PMNL that migrated into the airspaces were PMNL(BrdU) compared to 50.8+/-8% PMNL(BrdU) in the pulmonary capillaries . In vitro studies showed PMNL(BrdU) released from the bone marrow by G-CSF are less deformable than unlabelled circulating PMNL (p<0.01) . It is concluded that granulocyte colony-stimulating factor treatment causes the marrow to release polymorphonuclear leukocytes that preferentially sequester in lung microvessels but are slow to migrate out of the vascular space into the airspace at the pneumonic site.

Indian J Pediatr, 2000 May, 67(5), 337 - 8
Value of superficial cultures in diagnosing neonatal sepsis; Shenoy S et al.; This study was conducted to determine the value of superficial cultures in the diagnosis of neonatal sepsis in our hospital . Sixty three babies, younger than 2 weeks who were admitted with suspected sepsis were investigated . A total of 369 cultures were obtained from these babies--252 (68.29%) superficial and 171 (31.70%) deep cultures . External ear canal swab, umbilical cord swab and throat swab culture accounted for the superficial cultures . Blood culture, cerebrospinal fluid culture and i.v . catheter culture accounted for deep cultures . Of the 369 cultures, 225 (60.97%) were positive for pathogens, which included Staphylococcus aureus, Klebsiella sp, Escherichia coli, Group B streptococcus and Enterococcus fecalis . The yield of pathogenic organisms was higher for superficial cultures (53.84%) . All superficial cultures obtained during the study on each patient were simultaneously compared with the deep cultures by antimicrobial sensitivity method . The overall comparison showed that the practice of superficial cultures could be useful to predict the pathogenic organisms causing invasive disease.

Infection, 1999, 27(4-5), 259 - 60
Streptococcal toxic shock syndrome in two patients infected by a colonized surgeon; Rutishauser J et al.; The incidence of severe invasive infections caused by Streptococcus pyogenes, a group A streptococcus (GAS), has increased in the past 10 years . Most cases occur outside of the hospital setting . We report on two patients with nosocomial streptococcal toxic shock syndrome (StrepTSS) . In patient 1 the syndrome was associated with the development of necrotizing fasciitis following inguinal hernia repair . Patient 2 suffered from StrepTSS shortly after receiving a tetanus vaccine in her left deltoid . Epidemiologic investigations of these cases, which were noted within 48 hours of each other, showed that the same surgeon performed the vaccination on patient 2 after assisting a colleague during the hernia repair procedure on patient 1 . He was found to be a nasal carrier of GAS . All GAS isolates from the patients and the surgeon were indistinguishable by pulsed field gel electrophoresis . PCR analysis demonstrated the presence of streptococcal pyogenic exotoxins A and F . All strains were of the T-1 serotype and possessed the gene for M-protein 1 . This report demonstrates that a virulent strain of GAS may be spread by asymptomatically colonized medical personnel via the air route.

Infection, 1999, 27 Suppl 2, S32 - 4
Antimicrobial resistance--pharmacological solutions; Rubinstein E; The interaction between microbial resistance and antibacterial agents occurs in a direct and an indirect fashion . Directly--through the development of resistance to the agent used, or to agents of the same class--as exemplified by the induction of beta-lactamase by both gram-positive and gram-negative bacteria . It also takes place through the development of resistance to compounds of different classes to the compound used, as exemplified by the loss of Streptococcus pneumoniae susceptibility to penicillin that is accompanied by a parallel loss of sensitivity to erythromycin and to tetracycline . As for the indirect way--microbial resistance may develop through selection of resistant organisms when the patient is treated with antibiotics, when the environment is contaminated with antibiotics (hospital) or when antibacterial agents are used in agriculture and animal husbandry.

J Antimicrob Chemother, 2000 Jul, 46(1), 95 - 9
A novel antibacterial agent derived from the C-terminal domain of streptococcus mutans GTP-binding protein; Ohk SH et al.; A decapeptide, P1, homologous to part of the Streptococcus mutans G-protein (SGP) and the Escherichia coli Era protein, was synthesized and examined for growth-inhibitory effects . When P1 10 mg/L was added to E . coli DH5, the viability of the cells was reduced by 13% . Addition of lauric acid enhanced the bactericidal effects of P1 (68% killing in the presence of P1 plus lauric acid) . Similar enhancements were observed for mono lauroyl-rac-glycerol (MLG) and sodium dodecyl sulphate (SDS) . In cultures treated with both P1 and MLG, there were more elongated cells than in cultures treated with detergent or peptide alone . As with E . coli, the bactericidal effects of P1 on S . mutans were significantly enhanced in the presence of the detergent lauric acid . The combination of the two effectors produced >90% killing of S . mutans . Likewise, the combined action of P1 plus lauric acid reduced the viability of Listeria monocytogenes . P1 did not appear to be toxic to human gingival epithelial cells when added at concentrations < or = 1000 mg/L . Therefore, P1 has properties which could allow it to be used as an antibacterial agent.

J Antimicrob Chemother, 2000 Jul, 46(1), 19 - 26
Apoptosis, oxidative metabolism and interleukin-8 production in human neutrophils exposed to azithromycin: effects of Streptococcus pneumoniae; Koch CC et al.; Pathogen virulence factors and the host inflammatory response cause tissue injury associated with respiratory tract infections . The azalide azithromycin has demonstrated efficacy in the treatment of these infections . It has been demonstrated previously that induction of polymorphonuclear leucocyte (PMN) apoptosis is associated with minimization of tissue damage and inflammation in the lung . We hypothesized that, in addition to its antibacterial effects, azithromycin may promote apoptosis . The aim of the study was to determine the effects of azithromycin on PMN apoptosis, oxidative function and interleukin-8 (IL-8) production in the presence or absence of Streptococcus pneumoniae, in comparison with penicillin, erythromycin, dexamethasone or phosphate-buffered saline . Human circulating PMNs were assessed for apoptosis (by annexin V labelling and ELISA), oxidative function (by nitroblue tetrazolium reduction) and IL-8 production (by ELISA) . Azithromycin significantly induced PMN apoptosis in the absence of S . pneumoniae after 1 h (10.27% +/- 1.48%, compared with 2.19% +/- 0.42% in controls) to levels similar to those after 3 h induction with tumour necrosis factor-alpha (8 . 73% +/- 1.86%) . This effect was abolished in the presence of S . pneumoniae . Apoptosis in PMNs exposed to the other drugs was not significantly different from that in controls . Azithromycin did not affect PMN oxidative metabolism or IL-8 production . In summary, azithromycin-induced PMN apoptosis may be detected in the absence of any effect on PMN function, and the pro-apoptotic properties of azithromycin are inhibited in the presence of S . pneumoniae.

J Infect Dis, 2000 Jul, 182(1), 347 - 50 Epub 2000 Jul 06.
Effects of clinically used antioxidants in experimental pneumococcal meningitis; Auer M et al.; Reactive oxygen intermediates mediate brain injury in bacterial meningitis . Several antioxidant drugs are clinically available, including N-acetylcysteine (NAC), deferoxamine (DFO), and trylizad-mesylate (TLM) . The present study evaluated whether these antioxidants are beneficial in a model of pneumococcal meningitis . Eleven-day-old rats were infected intracisternally with Streptococcus pneumoniae and randomized to intraperitoneal treatment every 8 h with NAC (200 mg/kg), DFO (100 mg/kg), TLM (10 mg/kg), or saline (250 microL) . TLM-treated animals showed a significantly reduced mortality compared with controls (P<.03) . Meningitis led to extensive cortical injury at 22+/-2.2 h after infection (median, 14 . 6% of cortex; range, 0-61.1%) . Injury was significantly (P<.01) reduced to 1.1% (range, 0-34.6%) by NAC, to 2.3% (range, 0-19.6%) by DFO, and to 0.2% (range, 0-36.9%) by TLM (the difference was not significant among the 3 groups) . None of the drugs reduced hippocampal injury . Thus, several clinically used antioxidants reduced cortical injury in experimental pneumococcal meningitis.

J Infect Dis, 2000 Jul, 182(1), 150 - 7 Epub 2000 Jun 30.
Group B streptococcal beta-hemolysin induces nitric oxide production in murine macrophages; Ring A et al.; Group B streptococcus (GBS) is the leading cause of sepsis in neonates . Nitric oxide (NO) release plays a role in the hypotension that characterizes septic shock . To examine the role of the GBS beta-hemolysin in NO production, the murine macrophage line RAW 264 . 7 was exposed to a wild-type (WT) GBS isolate and to hyperhemolytic (HH) and nonhemolytic (NH) transposon mutants derived from that isolate . After activation of macrophages by the WT strain, the HH mutant, or cell-free extracts of beta-hemolysin, nitrite release into the supernatant increased >10-fold and inducible NO synthase (iNOS) levels in cell lysates increased up to 10-fold compared with treatment with the NH mutant or extracts from that mutant . Hemolysin-induced NO production was dependent on protein tyrosine kinases and NF-kappaB, but not on extracellular signal-related kinase-1/2-mitogen-activated kinases or protein kinase A . These results indicate that GBS beta-hemolysin induces murine macrophage iNOS via intracellular pathways similar to those that mediate lipopolysaccharide-induced iNOS activation.

J Antimicrob Chemother, 2000 Jul, 46(1), 35 - 43
Pharmacodynamic studies of trovafloxacin and grepafloxacin in vitro against Gram-positive and Gram-negative bacteria; Odenholt I et al.; Grepafloxacin and trovafloxacin are two novel fluoroquinolones with extended Gram-positive bacterial spectra compared with older quinolones . The aim of the present study was to investigate the different pharmacodynamic parameters of grepafloxacin in comparison with those of trovafloxacin . The following studies were performed against various Gram-positive and Gram-negative bacteria: (i) determination of the rate and extent of killing at a concentration corresponding to the 1 h non-protein-bound human serum level following an oral dose of 800 mg grepafloxacin and 300 mg trovafloxacin; (ii) determination of the rate and extent of killing of the two quinolones at different concentrations; (iii) determination of the post-antibiotic effects (PAEs); (iv) determination of the post-antibiotic sub-MIC effects (PA SMEs); (iv) determination of the rate and extent of killing in an in vitro kinetic model . It was shown that both grepafloxacin and trovafloxacin exhibited concentration-dependent killing against both Gram-positive and Gram-negative bacteria . Grepafloxacin exhibited a slower bactericidal effect against all the Gram-positive strains investigated in comparison with trovafloxacin in spite of a similar C(max)/MIC in the static experiments and a similar AUC/MIC ratio in the kinetic experiments . No major differences in the extent and rate of killing were noted against the Gram-negative strains, which were killed almost completely after 3 h except for Pseudomonas aeruginosa . A PAE of both quinolones was noted for all strains investigated . Trovafloxacin induced longer PAEs against the Gram-positive strains but shorter PAEs in comparison with those of grepafloxacin against the Gram-negative strains . A prolonging of the PAEs was noted for all bacteria when exposed to sub-MICs in the post-antibiotic phase . With a similar AUC/MIC of 310 for the penicillin-sensitive strain of Streptococcus pneumoniae and 143 for the penicillin-resistant strain, the time for 99.9% eradication for both strains was 2 h for trovafloxacin and 6 h for grepafloxacin.

J Infect Dis, 2000 Jul, 182(1), 158 - 67 Epub 2000 Jun 30.
Antibody to capsular polysaccharide of Streptococcus pneumoniae at the time of hospital admission for Pneumococcal pneumonia; Musher DM et al.; IgG to capsular polysaccharide (CPS) of Streptococcus pneumoniae is thought to provide the greatest degree of protection against pneumococcal disease . Serum obtained at hospital admission from 14 (27%) of 51 patients with bacteremic pneumococcal pneumonia and 11 (37%) of 30 with nonbacteremic pneumococcal pneumonia contained IgG to CPS of the infecting serotype; these percentages are similar to the prevalence of IgG to CPS in a control population . However, when compared with antibody from healthy adults, this IgG had far less capacity to opsonize the infecting pneumococcal serotype for phagocytosis in vitro by normal human polymorphonuclear leukocytes or to protect mice against experimental challenge . Failure to opsonize correlated closely with failure to protect mice, and each of these parameters correlated well with poor avidity for CPS . Future vaccine studies may need to examine the functional capacity of antibodies as a surrogate for infection, in addition to measuring their concentration in serum.

Clin Pediatr (Phila), 2000 Jun, 39(6), 317 - 26
Group B streptococcal infection early onset disease controversies in prevention guidelines, and management strategies for the neonate; Turow J et al.; Group B streptococcus (GBS) has been a major pathogen that is particularly devastating to the newborn for more than two decades . Initial guidelines were promoted by the AAP in 1992 to help deal with this organism, but these recommendations were poorly accepted and not widely used . In 1996-1997 the AAP, CDC, and ACOG created new guidelines for the management of the mother and infant at risk for GBS . Though usually in agreement, these three sets of recommendations still have some differences that may be confusing to the pediatrician . This paper looks at the acquisition, intrapartum treatment, and postnatal management of GBS, along with some of the controversies associated with the management of this disease.

Infection, 2000 May-Jun, 28(3), 175 - 7
Pneumococcal cellulitis in an HIV-infected adult; Mofredj A et al.; Streptococcus pneumoniae is an uncommon cause of cellulitis . In almost all of the reported cases, the infection occurred in immunosuppressed patients, especially in those with connective tissue diseases . We report a case of cervical cellulitis associated with septicemia which occurred in an HIV-infected adult.

Scand J Infect Dis, 2000, 32(3), 339 - 40
Serotypes and antimicrobial susceptibility of group B streptococcus isolated from neonates in Casablanca; Aitmhand R et al.; The serotypes and the levels of antibiotic resistance of 59 Streptococcus agalactiae isolates from neonates in Casablanca, from February 1992 to July 1997, were studied . Most of the isolates (86.4%) were recovered from early-onset disease . The serotype distribution was as follows: serotype III 39%; serotype Ia 32.2%; and serotype V 10.2% . All strains were susceptible to penicillin G, cefotaxime and ampicillin, whereas 1 strain was resistant to erythromycin . No high level of resistance to gentamicin was detected . A vaccine should comprise the most prevalent serotypes and also provide protection against serotype V disease . The antibiotic susceptibility patterns reported here support the recommended treatment and prophylaxis of invasive group B Streptococcal disease.

Scand J Infect Dis, 2000, 32(3), 322 - 3
Streptococcus salivarius acute meningitis with latent petromastoiditis; Megarbane B et al.; A 48-y-old woman, with a previous history of neurosurgical intervention for a trigeminal neurinoma, presented with acute meningitis due to Streptococcus salivarius . There were significant changes in the petrous region, as revealed by MRI, leading to the diagnosis of associated latent subacute mastoiditis.

Biosci Biotechnol Biochem, 2000 May, 64(5), 1106 - 9
Identification of a new gene responsible for the oxygen tolerance in aerobic life of Streptococcus mutans; Yamamoto Y et al.; Alkyl hydroperoxide reductase in Streptococcus mutans consists of two components, Nox-1 and AhpC . Deletion of nox-1 and ahpC in a double mutant as well as the wild-type of Streptococcus mutans can form colonies in the presence of air to the same extent . The evidence suggested the presence of some other antioxidant system(s) independent of the Nox-1/AhpC system in the bacterium . Here we identified a new antioxidant gene (dpr) and the gene product (Dpr) which complements the defect of peroxidase activity caused by the deletion of nox-1 and ahpC in S . mutans . The dpr-disruption mutant of S . mutans could form colonies anaerobically but not aerobically.

J Perinatol, 2000 Jun, 20(4), 225 - 30
Cytokines enhance opsonophagocytosis of type III group B Streptococcus; Campbell JR et al.; Neutrophil (polymorphonuclear leukocyte (PMN)-mediated killing is important to host defense against type III group B Streptococcus (GBS) . In neonates, a qualitative and quantitative deficiency in PMN-mediated host defense may contribute to an impaired neonatal response to this pathogen . OBJECTIVE: The purpose of this study was to determine whether tumor necrosis factor-alpha (TNF-alpha), granulocyte colony-stimulating factor (G-CSF), or granulocyte-macrophage colony-stimulating factor (GM-CSF) would enhance neonatal PMN-mediated killing of III GBS . STUDY DESIGN: PMNs from adults or neonates were incubated with TNF-alpha, G-CSF, or GM-CSF; next, PMN-mediated killing of III GBS was assessed in an in vitro opsonophagocytic assay . RESULTS: Treatment of PMNs with these cytokines for an interval of 5 minutes before addition of GBS to the reaction mixture enhanced opsonophagocytosis of bacteria both by adult PMNs and neonatal PMNs . The effect was statistically significant for TNF-alpha- and GM-CSF-treated adult PMNs and for GM-CSF-treated neonatal PMNs . The enhanced killing of III GBS by GM-CSF-treated PMNs was reduced by monoclonal antibody blockade of FcRIII . CONCLUSION: G-CSF enhances the neonatal PMN-mediated killing of III GBS in vitro . These studies suggest that use of FcRIII receptors may be one mechanism by which GM-CSF augments the PMN-mediated killing of III GBS . The addition of purified immunoglobulin G containing III GBS-specific antibody facilitated opsonophagocytosis by GM-CSF-treated PMNs . We speculate that the administration of GM-CSF alone or in combination with intravenous immunoglobulin may improve the neonatal host response to III GBS.

Lik Sprava, 2000 Jan-Feb, (1), 79 - 82
{The development of a treatment method for streptococcal tonsillitis in children}; Marushko IuV; Kept under continuous medical surveillance were 77 children with streptococcal tonsillitis . In all patients, a pathogenic streptococcus (GABHS) was invariably found in culture . Among other common features of the above disease were decline in the tonsil colony resistance state and lowering of those parameters characterizing immunity . A highly efficient means of treating tonsillitis of streptococcal etiology has been elaborated, relying on the use of macrolides and L . acidophilus according to our methods, which can, we believe, come to be widely used in health care practice.

Rev Esp Quimioter, 1999 Sep, 12(3), 255 - 63
{Effect of subinhibitory concentrations of various antimicrobials on insoluble glucan production, polystyrene adherence and bacterial surface hydrophobicity of Streptococcus sobrinus}; Heredia S et al.; The effect of subinhibitory concentrations (1/2, 1/4, 1/8 of the MIC) of amoxicillin, teicoplanin, clindamycin and erythromycin on the factors influencing the adherence and pathogenicity of Streptococcus sobrinus was evaluated . These factors included insoluble glucan, polystyrene adherence and bacterial surface hydrophobicity . Insoluble glucan was detected using a spectrophotometric method; polystyrene adherence was assessed using microtiter plates; and surface hydrophobicity was determined using a biphasic system (water/p-xiline) . Amoxicillin and teicoplanin induced a statistically significant decrease in adherence at subinhibitory concentrations, and they also decreased the hydrophobicity . However, clindamycin and erythromycin were unable to decrease these parameters . The adherence and hydrophobicity of S . sobrinus was also dependent on the concentration of sucrose in the culture medium.

Microbiology, 2000 Jul, 146 ( Pt 7), 1661 - 70
Investigation of the translation-initiation factor IF2 gene, infB, as a tool to study the population structure of Streptococcus agalactiae; Hedegaard J et al.; The sequence of infB, encoding the prokaryotic translation-initiation factor 2 (IF2), was determined in eight strains of Streptococcus agalactiae (group B streptococcus) and an alignment revealed limited intraspecies diversity within S . agalactiae . The amino acid sequence of IF2 from S . agalactiae and from related species were aligned and revealed an interspecies conserved central and C-terminal part, and an N-terminal part that is highly variable in length and amino acid sequence . The diversity and relationships in a collection of 58 genetically distinct strains of S . agalactiae were evaluated by comparing a partial sequence of infB . A total of six alleles were detected for the region of infB analysed . The alleles correlated with the separation of the same strains of S . agalactiae into major evolutionary lineages, as shown in previous work . The partial sequences of infB were furthermore used in phylogenetic analyses of species closely related to S . agalactiae, yielding an evolutionary tree which had a topology similar to a tree constructed using 16S rRNA sequences from the same species.

Microbiology, 2000 Jul, 146 ( Pt 7), 1565 - 72
The mannitol-specific enzyme II (mtlA) gene and the mtlR gene of the PTS of Streptococcus mutans; Honeyman AL et al.; The phosphoenolpyruvate-dependent phosphotransferase system (PTS) is widely found among Gram-positive bacteria . It is the major source of carbohydrate transport in the dental pathogen Streptococcus mutans . The transported carbohydrates are fermented to produce large amounts of lactic acid which initiates dental caries . The authors have isolated the S . mutans gene for the mannitol-specific Enzyme II (EII) component of the PTS, mtlA, and the adjacent mtlR gene, which is located in the same operon . The mtlR gene is located between mtlA and the genes mtlF and mtlD . The nucleotide sequence of the mtlA and mtlR loci has been determined . The deduced mtlA gene product of S . mutans consists of 589 amino acids with a molecular mass of 62.0 kDa . It exhibits similarity with the mtlA gene products from other organisms . However, the similarity between these proteins is generally restricted to the 470 amino-terminal residues of the S . mutans protein . This region would correspond to the EIICB domains of the PTS . The authors have previously shown that the S . mutans mtlF gene product exhibits 76.6% similarity to the carboxyl-terminal 143 amino acids of the Escherichia coli mtlA product and that the mtlF gene encodes the EIIA domain of the PTS . Thus, the genes that encode the EIICB and the EIIA domains are separated by approximately 2250 bp . In many organisms, all of the EII domains may be fused together to form one molecule . The fact that these domains are separated by this distance in S . mutans supports the hypothesis that various functional domains of the PTS have been rearranged during evolution . The sequence of the 119 carboxyl-terminal amino acids of the S . mutans mtlA gene product also displays homology to the carboxyl-terminal end of the EIIB domain of various mannitol PTSs . Thus, this domain may have been duplicated in S . mutans during evolution of the operon . The mtlR gene is located in the same operon structure as mtlA but these loci are separated by an intragenic space . The precise 5' end of the mtlR locus cannot be determined either by in vitro transcription-translation assays or based upon nucleotide sequence analysis because of the apparent lack of a ribosome-binding site preceding the gene . The deduced mtlR gene product, which consists of approximately 650 amino acids with a molecular mass of 75.3 kDa, exhibits limited similarity to several potential transcriptional regulators . However, the exact function of this locus is currently unknown.

Microbiology, 2000 Jul, 146 ( Pt 7), 1547 - 53
The bacA gene, which determines bacitracin susceptibility in Streptococcus pneumoniae and Staphylococcus aureus, is also required for virulence; Chalker AF et al.; Homologues of Escherichia coli bacA, encoding extremely hydrophobic proteins, were identified in the genomes of Staphylococcus aureus and Streptococcus pneumoniae . Allelic replacement mutagenesis demonstrated that the gene is not essential for in vitro growth in either organism, and the mutants showed no significant changes in growth rate or morphology . The Staph . aureus bacA mutant showed slightly reduced virulence in a mouse model of infection and an eightfold increase in bacitracin susceptibility . However, a Strep . pneumoniae bacA mutant was highly attenuated in a mouse model of infection, and demonstrated an increase in susceptibility to bacitracin of up to 160000-fold . These observations are consistent with the previously proposed role of BacA protein as undecaprenol kinase.

J Clin Microbiol, 2000 Jul, 38(7), 2760 - 2
Immunoglobulin A1 protease activity in Gemella haemolysans; Lomholt JA et al.; The purpose of this study was to determine the occurrence and nature of immunoglobulin A1 (IgA1) protease activity in members of the genus Gemella and related taxa . Among a total of 22 Gemella strains belonging to the four species Gemella haemolysans, Gemella morbillorum, Gemella sanguinis, and Gemella bergeriae and four reference strains of the species Helcococcus kunzii, Facklamia hominis, and Globicatella sanguinis, IgA1 protease activity was an exclusive character of all nine isolates of G . haemolysans . The IgA1 protease of G . haemolysans appears to be a metallo-type IgA1 protease that cleaves the Pro(227)-Thr(228) peptide bond in the hinge region of the alpha1 chain like that of several Streptococcus species . Phenotypic characterization of the isolates demonstrates that screening for IgA1 protease activity provides a valuable means for species differentiation in this group of bacteria.

J Biol Chem, 2000 Sep 15, 275(37), 28971 - 83
The DNA replication machine of a gram-positive organism; Bruck I et al.; This report outlines the protein requirements and subunit organization of the DNA replication apparatus of Streptococcus pyogenes, a Gram-positive organism . Five proteins coordinate their actions to achieve rapid and processive DNA synthesis . These proteins are: the PolC DNA polymerase, tau, delta, delta', and beta . S . pyogenes dnaX encodes only the full-length tau, unlike the Escherichia coli system in which dnaX encodes two proteins, tau and gamma . The S . pyogenes tau binds PolC, but the interaction is not as firm as the corresponding interaction in E . coli, underlying the inability to purify a PolC holoenzyme from Gram-positive cells . The tau also binds the delta and delta' subunits to form a taudeltadelta' "clamp loader." PolC can assemble with taudeltadelta' to form a PolC.taudeltadelta' complex . After PolC.taudeltadelta' clamps beta to a primed site, it extends DNA 700 nucleotides/second in a highly processive fashion . Gram-positive cells contain a second DNA polymerase, encoded by dnaE, that has homology to the E . coli alpha subunit of E . coli DNA polymerase III . We show here that the S . pyogenes DnaE polymerase also functions with the beta clamp.

Carbohydr Res, 2000 Jun 2, 326(2), 98 - 103
Nigerooligosaccharide acceptor reaction of Streptococcus sobrinus glucosyltransferase GTF-I; Mukasa H et al.; Nigerose and nigerooligosaccharides served as acceptors for a glucosyltransferase GTF-I from cariogenic Streptococcus sobrinus to give a series of homologous acceptor products . The soluble oligosaccharides (dp 5-9) strongly activated the acceptor reaction, resulting in the accumulation of water-insoluble (1-->3)-alpha-D-glucan . The enzyme transferred the labeled glucosyl residue from D-{U-13C}sucrose to the 3-hydroxyl group at the non-reducing end of the (1-->3)-alpha-D-oligosaccharides, as unequivocally shown by NMR 13C-13C coupling patterns . The values of the 13C-13C one-bond coupling constant (1J) are also presented for the C-1-C-6 of the 13C-labeled alpha-(1-->3)-linked glucosyl residue and of the non-reducing-end residue.

Aten Primaria, 2000 May 15, 25(8), 542 - 5
{Streptococcus pyogenes: in vitro susceptibility and role of beta-lactamase producing bacteria in the persistence of streptococcal pharyngotonsillitis}; Gonzalez Pedraza Aviles A et al.; OBJECTIVE: To assess the frequency of association between Streptococcus pyogenes and beta-lactamase-producing-bacteria in the pharyngotonsillitis and the evaluate the in vitro susceptibility . DESIGN: Prospective, descriptive, transverse study . SETTING: The present study was carried out in the Health Center Dr . Jose Castro Villagrana, in Tlalpan, Mexico, D.F., from Juanary, 1996 to February 1999 . PARTICIPANTS: In three hundred and ninety four patients with pharyngotonsillitis diagnosis we isolated the same number of Streptococcus pyogenes, and possible beta-lactamase-producing-bacteria . RESULTS: In 180 patients (45.7%) we isolated at least one possible beta-lactamase-producing-bacteria . Of these, in 138 patients (35%) were confirmed the enzyme presence . In total, we isolated 218 possible beta-lactamase-producing bacteria, and 152 (69.7%) were beta-lactamase positive . We found no significant change in the in vitro susceptibility of group A Streptococcus to penicillin, but erythromycin resistance is relatively common, approximately 10% in this study . CONCLUSIONS: Streptococcus pyogenes was uniformly susceptible to all penicillins and cephalosporins in vitro . Erythromycin treatment should not be promoted as first-line therapy because the consequent increase of bacterial resistance could create difficulty in treating penicillin-allergic patients . Because of the poor activity of trimetoprimsulfametoxazol, this drug no longer can be considered the drug of choice for the management of group A Streptococcal infections.

Pediatrics . 2000 Jul;106(1):E4.
Use of C-reactive protein in minimizing antibiotic exposure: experience with infants initially admitted to a well-baby nursery; Philip AG et al.; OBJECTIVE: To evaluate the use of a clinical pathway for neonatal sepsis in decisions about initiating and continuing antibiotic treatment . SETTING: A district hospital primarily served by private pediatricians practicing in a managed care environment . PATIENTS AND LABORATORY TESTS: All infants admitted to the well-baby nursery in 1997-1998 were eligible for this study . Infants born with a variety of risk factors (eg, borderline prematurity, membranes ruptured for over 18 hours, mother positive for group B streptococcus {GBS}, and maternal fever) or clinical manifestations suggesting possible infection (either clinical signs or persistent hypoglycemia) were evaluated with white blood cell count, differential, and C-reactive protein (CRP) soon after birth and 12 hours later . Decisions to transfer to the neonatal intensive care unit and to treat with antibiotics were based on abnormal laboratory test results, particularly an increased level of CRP (>1 mg/dL), persistent hypoglycemia, or clinical signs . Discontinuation of antibiotic treatment was primarily based on return to normal of the CRP . RESULTS: Of 8299 live births, 7562 initially went to the well-baby nursery . Evaluation occurred in 1894 (25%) and 425 were transferred to the neonatal intensive care unit . In 162, antibiotics were discontinued within 48 hours . The majority were treated for 3 to 5 days, with only 19 (3 with GBS sepsis) treated for 6 days or more . There were 216 infants transferred because of risk factors and 209 because of clinical findings . Peak CRP primarily determined the duration of antibiotic treatment, with the mean peak CRP rising from 2.8 mg/dL in those treated for 3 days, to 3.8, 4.3, 8.4, 8.9, and 13 . 7 mg/dL in those treated for 4, 5, 6, 7, or >7 days, respectively . The mean duration of treatment was 3.1 days . No infant initially treated with antibiotics and discharged when the CRP returned to normal was readmitted within the next month . No infant with normal values on the sepsis screen was readmitted within 1 month with evidence of bacterial infection, but 1 infant with no risk factors was readmitted at 22 days of age with GBS sepsis and meningitis . CONCLUSIONS: Using a clinical pathway for neonatal sepsis, which is based primarily on CRP determinations, can minimize antibiotic exposure and shorten hospital stays.

Res Microbiol, 2000 May, 151(4), 285 - 9
Lack of GATC sites in the genome of Streptococcus bovis bacteriophage F4; Styriak I et al.; A strong bias against GATC sites was observed in the genome of phage F4, a lytic Streptococcus bovis bacteriophage . Only three GATC sites were found within the 60.4-kbp genome of this phage . The comparative lack of GATC sequences within the F4 genome was probably not due to dam methylation, as no modification within this site was detected using methylation-sensitive isoschizomer pair restriction endonuclease analysis . The short oligonucleotide composition of available S . bovis DNA sequences suggested the existence of an unknown mechanism for counterselection of GATC sites in S . bovis bacteriophages.

J Perinat Med, 2000, 28(2), 129 - 32
The significance of interleukin-6 concentrations in cervicovaginal fluid: its relation to umbilical cord plasma and the influence of antibiotic treatment; Matsuda Y et al.; This study was performed to correlate cervicovaginal fluid and umbilical cord plasma level of IL-6 and IL-8 in patients with premature rupture of the membranes (PROM) and to see the effect of antibiotics on those concentrations . As a part of a randomized controlled trial of treatment in PROM with antibiotics, cervicovaginal fluid was sampled before delivery for measurement of IL-6 and IL-8 and for bacteria from 36 patients less than 36 weeks of gestation . Umbilical cord plasma was also collected . Concentrations of IL-6 and IL-8 were measured by an ELISA . Neonatal infections were noted in a total of 9 cases, including bacteria detection (Escherichia coli 2 cases, GBS and Streptococcus constellata) in 4 cases . Correlation between IL-6 in cervicovaginal fluid and in cord plasma (r = 0.881, p < 0.0001) was stronger than that of IL-8 (r = 0.469, p < 0.01) . The difference of concentrations in IL-6 and IL-8 was not significant between cases with (n = 20) and without (n = 16) ampicillin . Our observation indicates that the measurement of IL-6 concentrations in cervicovaginal fluid is a useful marker for PROM patients who are more likely to develop neonatal infection and the antibiotic treatment does not necessarily produce their beneficial effects on fetuses at the risk of infection.

Philos Trans R Soc Lond B Biol Sci, 2000 May 29, 355(1397), 657 - 65
Virulence gene regulation inside and outside; DiRita VJ et al.; Much knowledge about microbial gene regulation and virulence is derived from genetic and biochemical studies done outside of hosts . The aim of this review is to correlate observations made in vitro and in vivo with two different bacterial pathogens in which the nature of regulated gene expression leading to virulence is quite different . The first is Vibrio cholerae, in which the concerted action of a complicated regulatory cascade involving several transcription activators leads ultimately to expression of cholera toxin and the toxin-coregulated pilus . The regulatory cascade is active in vivo and is also required for maintenance of V . cholerae in the intestinal tract during experimental infection . Nevertheless, specific signals predicted to be generated in vivo, such as bile and a temperature of 37 degrees C, have a severe down-modulating effect on activation of toxin and pilus expression . Another unusual aspect of gene regulation in this system is the role played by inner membrane proteins that activate transcription . Although the topology of these proteins suggests an appealing model for signal transduction leading to virulence gene expression, experimental evidence suggests that such a model may be simplistic . In Streptococcus pyogenes, capsule production is critical for virulence in an animal model of necrotizing skin infection . Yet capsule is apparently produced to high levels only from mutation in a two-component regulatory system, CsrR and CsrS . Thus it seems that in V . cholerae a complex regulatory pathway has evolved to control virulence by induction of gene expression in vivo, whereas in S . pyogenes at least one mode of pathogenicity is potentiated by the absence of regulation.

Ann Fr Anesth Reanim, 2000 May, 19(5), 360 - 2
{Meningitis after spinal anesthesia}; Varlet C et al.; The occurrence of meningitis after spinal anaesthesia is a very rare event . We report a case of Streptococcus sanguis meningitis following spinal anaesthesia for orthopaedic material removal . The presence of Gram positive cocci (Streptococcus sanguis) in the cerebrospinal fluid was in favour of an exogenous contamination, originating either from the patient's skin or the anaesthesiologist's oropharynx . The outcome was uneventful . The responsibility of the latter can result in legal consequences . The scrupulous compliance with guidelines prevents this risk.

J Am Acad Orthop Surg, 2000 May-Jun, 8(3), 151 - 8
Necrotizing soft-tissue infections; Fontes RA Jr et al.; Necrotizing fasciitis is a rare and often fatal soft-tissue infection involving the superficial fascial layers of the extremities, abdomen, or perineum . Necrotizing fasciitis typically begins with trauma; however, the inciting event may be as seemingly innocuous as a simple contusion, minor burn, or insect bite . Differentiating necrotizing infections from common soft-tissue infections, such as cellulitis and impetigo, is both challenging and critically important . A high degree of suspicion may be the most important aid in early diagnosis . Prompt diagnosis is imperative because necrotizing infections typically spread rapidly and can result in multiple-organ failure, adult respiratory distress syndrome, and death . Although group A Streptococcus is the most common bacterial isolate, a polymicrobial infection with a variety of Gram-positive, Gram-negative, aerobic, and anaerobic bacteria is more common . Orthopaedic surgeons are often the first physicians to evaluate patients with such infections and therefore need to be familiar with this potentially devastating disease and its management . Prompt diagnosis, immediate administration of broad-spectrum antibiotic coverage, and emergent aggressive surgical debridement of all compromised tissues are critical to reduce the morbidity and mortality of these rapidly progressing infections.

New Microbiol, 2000 Apr, 23(2), 119 - 28
Expression of measles virus antigens in Streptococcus gordonii; Maggi T et al.; The measles virus proteins haemagglutinin (HA) and fusion protein (F), which together mediate attachment and penetration of the virus in the host cell and can elicit production of neutralising antibodies in the course of natural infection were expressed in the vaccine vector Streptococcus gordonii, a Gram-positive bacterium normally present in the human oral cavity . HA and F were expressed as fusion proteins attached to the bacterial surface, and were both found to be immunogenic when the recombinant S . gordonii were inoculated subcutaneously in mice.

J Dent Res, 1987 Nov, 66(11), 1658 - 62
Comparison of the effects of fluoride and the ionophore nigericin on acid production by Streptococcus mutans and the resultant in vitro enamel demineralization; Van Loveren C et al.; In an in vitro demineralization experiment with a plaque of S . mutans C180-2 over enamel, the effect of 0.5 mmol fluoride/L was compared with that of 10 nmol nigericin/L . Since the effects of both substances on the acid production in a dense cell suspension were of the same magnitude, and since nigericin did not affect the enamel solubility, the present demineralization experiment may differentiate between the effect of fluoride on bacterial metabolism alone and the combined effect of fluoride on both the bacterial metabolism and enamel solubility . In our experiments, the effect on bacterial metabolism accounted for 75% of the caries-inhibiting effect of fluoride . Microradiographic data showed subsurface lesions in the control and nigericin group and a slight surface-softening in the fluoride group . In addition, the effects of fluoride and nigericin on the cellular internal pH during glycolysis were studied . Analysis of these data suggested that glycolysis was inhibited when the intracellular pH reached about pH 5.2, which supports the view that acidification of the cell cytoplasm is a mechanism by which fluoride inhibits glycolysis.

Med Oncol, 2000 May, 17(2), 111 - 6
Infections in acute leukemia: an analysis of 240 febrile episodes; Jagarlamudi R et al.; Infections are the major cause of morbidity and mortality in acute leukemia patients . Case records of 91 consecutive patients (AML-48, ALL-40, RAEB-t/AML-3) treated between January 1997 and July 1999 were studied to determine the type, frequency and severity of infections . Patients' median age was 36 y (range 6-66) and male to female ratio was 2.5:1 . A total of 240 febrile episodes were recorded; of them, 162 were associated with neutropenia (absolute neutrophil count, ANC<500/mm3) and 78 were without neutropenia . Among the neutropenic episodes, an infectious etiology could be documented in 52%; the remainder (48%) were defined as isolated febrile episodes . Chest was the most common site of infection (35 . 7%) followed by skin, soft tissue (13%), GIT (7%) and genitourinary tract (6%) infections in order of decreasing frequency . Microbiologically, gram positive organisms (staphylococcus aureus, coagulase negative staphylococcus, streptococcus, enterococcus) were the most common isolates (52.8%) followed by gram negative organisms (E . coli, klebsiella, pseudomonas) in 42.8% of isolates . Two patients had pulmonary tuberculosis and three patients had fungal infections (candida-2, aspergillus-1) . Among non-neutropenic patients, infection could be documented in 36%; the remaining 64% were isolated febrile episodes . Gram negative infections were documented in 50%, gram positive in 30% and fungal infections (candida-4, aspergillus-1, mucormycosis-1) in 20% of them . A combination of third generation cephalosporin and an aminoglycoside were used in 79% of episodes initially; a combination of a newer penicillin and aminoglycoside (4.6%), double betalactums (4.1%), oral antibiotics (9.8%) and others were used in the remaining episodes . Fever resolved in 38% of episodes using the above combinations; in the remainder second line antibiotics (mainly vancomycin) and antifungals (amphotericin-B) were added empirically or depending on culture and sensitivity . In 52.5% of episodes fever resolved after addition of second line antibiotics and antifungals . 11 of 91 patients died of infectious complications in this study . There is a need for improvised diagnostic tests to detect infections early as well as for new therapies to overcome antimicrobial resistance.

Arch Dis Child Fetal Neonatal Ed, 2000 Jul, 83(1), F48 - 9
Neonatal group B streptococcal disease associated with infected breast milk; Olver WJ et al.; Premature triplets each developed late onset group B streptococcal disease over a period of nine weeks . The source of the organism appeared to be expressed maternal breast milk, in the absence of clinical mastitis . Asymptomatic excretion of group B streptococcus in breast milk may be an under-recognised cause of neonatal infection.

Am J Forensic Med Pathol, 2000 Jun, 21(2), 151 - 4
Necrotizing fasciitis: reports of three fatal cases simulating and resulting from assaults; Rutty GN et al.; Necrotizing fasciitis is a progressive, potentially fatal, rapid, necrotizing infection of the subcutaneous tissues and fascia often caused by a mixture of organisms or by infection with group A Streptococcus pyogenes with or without Staphylococcus aureus . Three cases are presented that have been encountered in forensic pathologic practice . Two cases presented after assaults, and the third simulated an assault and burglary . The history, scene, and pathologic findings are presented with a brief review of the literature.

J Biol Chem, 2000 Sep 8, 275(36), 27768 - 74
Characterization of the murMN operon involved in the synthesis of branched peptidoglycan peptides in Streptococcus pneumoniae; Filipe SR et al.; The murMN operon, recently identified in the genome of Streptococcus pneumoniae, encodes for enzymes involved in the synthesis of branched structured muropeptides in the pneumococcal peptidoglycan; inactivation of murMN causes production of a peptidoglycan composed exclusively of linear muropeptides and a virtually complete loss of resistance in penicillin-resistant strains (Filipe, S . R., and Tomasz, A . (2000) Proc . Natl . Acad . Sci . U . S . A . 97, 4891-4896) . The experiments described in this paper follow up these observations . Primer extension analysis was used to identify the putative promoter region of the murMN operon in penicillin-susceptible and -resistant strains . Selective inactivation of the murN gene in the penicillin-resistant strain Pen6 caused production of an unusual peptidoglycan that contained only single amino acid residues in the muropeptide branches, indicating that the product of murN was involved with the addition of the second amino acid and the product of murM was involved with the addition of the first amino acid (alanine or serine) to the peptidoglycan cross-bridge . Allelic replacement of the mosaic murM gene of strain Pen6 with murM of the penicillin-susceptible laboratory strain caused enrichment of the peptidoglycan in linear muropeptides . The findings suggest that the genetic determinant primarily controlling the synthesis of branched muropeptides in the pneumococcal peptidoglycan is murM.

Hong Kong Med J, 1999 Dec, 5(4), 406 - 409
Emergence of Streptococcus pneumoniae with high-level resistance to cefotaxime in Hong Kong; Wong SS et al.; We report on two cases of pneumococcal infection caused by strains demonstrating high-level cefotaxime resistance (minimal inhibitory concentration, 4 microg/mL) . One patient had acute community-acquired meningitis with bacteraemia and the other had bacteraemia probably as a result of nosocomial pneumonia . Both patients died despite treatment with third generation cephalosporins . This is the first report from Hong Kong of infection with Streptococcus pneumoniae with high-level cefotaxime resistance that resulted in death . The emergence of high-level resistance to third-generation cephalosporins will result in treatment failure when these agents or penicillin are used alone, especially in cases of severe infection, such as meningitis, in which drug penetration of the blood-brain barrier is critical . The treatment of severe infections due to these isolates is problematic . Indiscriminate use of life-saving third-generation cephalosporins as out-patient treatment of minor infections or as first-line therapy for uncomplicated community-acquired infections in the hospital and in the community should be discouraged.

Respir Med, 2000 May, 94(5), 505 - 10
Community-acquired pneumonia: development of a bedside predictive model and scoring system to identify the aetiology; Ruiz-Gonzalez A et al.; Although initial presentation has been commonly used to select empirical therapy in patients with community-acquired pneumonia (CAP), few studies have provided a quantitative estimation of its value . The objective of this study was to analyse whether a combination of basic clinical and laboratory information performed at bedside can accurately predict the aetiology of pneumonia . A prospective study was developed among patients admitted to the Emergency Department University Hospital Arnau de Vilanova, Lleida, Spain, with CAP . Informed consent was obtained from patients in the study . At entry, basic clinical (age, comorbidity, symptoms and physical findings) and laboratory (white blood cell count) information commonly used by clinicians in the management of respiratory infections, was recorded . According to microbiological results, patients were assigned to the following categories: bacterial (Streptococcus pneumoniae and other pyogenic bacteria), virus-like (Mycoplasma pneumoniae, Chlamydia spp and virus) and unknown pneumonia . A scoring system to identify the aetiology was derived from the odds ratio (OR) assigned to independent variables, adjusted by a logistic regression model . The accuracy of the prediction rule was tested by using receiver operating characteristic curves . One hundred and three consecutive patients were classified as having virus-like (48), bacterial (37) and unknown (18) pneumonia, respectively . Independent predictors related to bacterial pneumonia were an acute onset of symptoms (OR 31; 95% CI, 6-150), age greater than 65 or comorbidity (OR 6.9; 95% CI, 2-23), and leukocytosis or leukopenia (OR 2; 95% CI, 0.6-7) . The sensitivity and specificity of the scoring system to identify patients with bacterial pneumonia were 89% and 94%, respectively . The prediction rule developed from these three variables classified the aetiology of pneumonia with a ROC curve area of 0.84 . Proper use of basic clinical and laboratory information is useful to identify the aetiology of CAP . The prediction rule may help clinicians to choose initial antibiotic therapy.

Caries Res, 2000 Jul-Aug, 34(4), 295 - 302
Studies concerning the glucosyltransferase of Streptococcus sanguis; Vacca Smith AM et al.; We have shown in previous studies that the glucosyltransferase (Gtf) enzymes of Streptococcus mutans have distinct properties when adsorbed to a surface . In the present study, we compared the activity of Gtf from Streptococcus sanguis, designated GtfSs, in solution and on the surface of saliva-coated hydroxyapatite (sHA) beads, and determined the ability of its product glucan to support the adherence of oral microorganisms . Gtf from S . sanguis 804 NCTC 10904 was purified from culture supernatant fluids by means of hydroxyapatite chromatography . Enzyme and the substrate were prepared in buffers at pH values from 3.5 to 7.5 . Maximum activity of GtfSs occurred between pH 5.5 and pH 6.5, whether in solution or adsorbed onto a surface . The solubilized and insolubilized enzymes showed highest activity at 40 degrees C; activity was reduced by 50(+/-2)% at 20 and 30 degrees C . The enzyme did not form glucans in either phase at 10 or 60 degrees C . The K(m), determined from Lineweaver-Burk plots, for the enzyme in solution was 4.3(+/-0.4) mmol/l sucrose, and the K(m) for the enzyme on sHA beads was 5.0(+/-1.0) mmol/l sucrose . The ability of the GtfSs glucan synthesized on the surface of sHA beads to support the adherence of oral bacteria was investigated . (3)H-thymidine-labeled bacteria (S . mutans GS-5, S . sobrinus 6715, S . sobrinus 6716, S . sanguis 10904, Actinomyces viscosus OMZ105E, A . viscosus 2085, and A . viscosus 2086) were incubated with sHA beads coated with GtfSs glucan . S . mutans GS-5 displayed the highest level of binding numerically . These results show that the GtfSs of S . sanguis is active on sHA beads, that the pH optimum for activity on a surface differs slightly from that in solution, and that its product glucan can support the adherence of oral microorganisms.

Rev Esp Enferm Dig, 2000 Apr, 92(4), 232 - 9
Pyogenic liver abscesses of bacterial origin . A study of 45 cases; Barrio J et al.; OBJECTIVE: to determine the clinical, microbiological, diagnostic and therapeutic characteristics of pyogenic liver abscesses of bacterial origin . METHODS: retrospective analysis of pyogenic liver abscesses diagnosed at the Aranzazu Hospital in San Sebastian (northern Spain) between 1989 and 1998 . RESULTS: we studied 45 patients with pyogenic liver abscesses of bacterial origin (30 men, 15 women, mean age 61 years 11 months) . The site of the liver abscess was biliary in 28.9% of the patients, portal in 11.1%, and unknown in 33.3% . Elevated erythrocyte sedimentation rate (95.5%), leukocytosis (86.7%) and fever (82.2%) were the most frequent clinical and laboratory findings . The abscesses were solitary in 55 . 5% of the patients . Echography was diagnostic in 68.4% of patients, and computed tomography was diagnostic in 100% . Cultures of pus from the abscess and blood were positive in 77.1% and 50% respectively . Of the abscesses diagnosed as being of bacterial origin, 44.4% involved multiple organisms . Escherichia coli and Streptococcus milleri were the germs isolated most frequently . Percutaneous drainage was done in 22 patients (48.9%), with satisfactory results in 18 . Overall mortality related with abscesses was 15.5% . CONCLUSIONS: the clinical presentation of pyogenic liver abscess did not vary during the study period . Computed tomography is fundamental for diagnosis and treatment . Percutaneous drainage associated with early antibiotic therapy is the treatment of choice.

FEMS Microbiol Lett, 2000 Jul 1, 188(1), 81 - 5
The fib locus in Streptococcus pneumoniae is required for peptidoglycan crosslinking and PBP-mediated beta-lactam resistance; Weber B et al.; Penicillin resistance in pneumococci is mediated by modified penicillin-binding proteins (PBPs) that have decreased affinity to beta-lactams . In high-level penicillin-resistant transformants of the laboratory strain Streptococcus pneumoniae R6 containing various combinations of low-affinity PBPs, disruption of the fib locus results in a collapse of PBP-mediated resistance . In addition, crosslinked muropeptides are highly reduced . The fib operon consists of two genes, fibA and fibB, homologous to Staphylococcus aureus femA/B which are also required for expression of methicillin resistance in this organism . FibA and FibB belong to a family of proteins of Gram-positive bacteria involved in the formation of interpeptide bridges, thus representing interesting new targets for antimicrobial compounds for this group of pathogens.

FEMS Microbiol Lett, 2000 Jul 1, 188(1), 75 - 9
Three-dimensional modelling of the catalytic domain of Streptococcus mutans glucosyltransferase GtfB; Tsai YW et al.; Glucosyltransferases (GtfB/C/D) of Streptococcus mutans, a pathogen for human dental caries, synthesize water-insoluble glucan through the hydrolysis of sucrose . Genetic and biochemical approaches have identified several active sites of these enzymes, but no three-dimensional (3D) structural evidence is yet available to elucidate the subdomain arrangement and molecular mechanism of catalysis . Based on a combined sequence and secondary structure alignment against known crystal structures of segments from closely related proteins, we propose here the 3D model of an N-terminal domain essential for the sucrose binding and splitting in GtfB . A Tim-barrel of (alpha/beta)(8) structural characteristics is revealed and the structural correlation for two peptides is described.

J Antibiot (Tokyo), 2000 Apr, 53(4), 345 - 50
SB-219383, a novel tyrosyl tRNA synthetase inhibitor from a Micromonospora sp . I . Fermentation, isolation and properties; Stefanska AL et al.; A novel, potent and selective inhibitor of bacterial tyrosyl tRNA synthetase, designated SB-219383 has been isolated from Micromonospora sp . NCIMB 40684 . The fermentation, isolation and some properties are described, whilst the structure determination is described in the succeeding paper) . SB-219383 showed competitive, inhibitory activity against a Staphylococcus tyrosyl tRNA synthetase, with an IC50 of <1 nM, and exhibited weak in vitro activity against some Streptococcus sp.

Vet Microbiol, 2000 Jul 3, 75(1), 27 - 41
Genomic typing of Streptococcus uberis isolates from cases of mastitis, in New Zealand dairy cows, using pulsed-field gel electrophoresis; Douglas VL et al.; Three hundred and forty-two Streptococcus uberis isolates were cultured from milk samples from subclinical and clinical cases of dairy cattle mastitis . The samples were collected from 15 different New Zealand farming regions, including eight specific farms, during field research trials and veterinary diagnostic investigations . Pulsed-field gel electrophoresis was used to determine and compare the degree of genetic dissimilarity between the restriction endonuclease fragment pattern of the 342 New Zealand and a single United States S . uberis isolate . The 343 isolates exhibited 330 different restriction endonuclease fragment patterns . The United States isolate had a pattern unlike any of the New Zealand isolates . Most of the isolates were genetically different strains (pattern deferred by at least 33%), but identical patterns were noted within the same or different quarters of an individual cow, different cows within the same farm, and from different cows from the same or different districts, farming regions or islands . Seven of the eight selected farms had at most only one pair of isolates with banding patterns, which differed by less than 33% . A high degree of dissimilarity was noted in individual herds in which all the samples were collected on the same day or over a 2-year period . The high degree of dissimilar isolates is an indication that S . uberis infections in New Zealand dairy cattle are largely due to the opportunistic nature of the organism in the cows' environment . Prevention and treatment of S . uberis mastitis will therefore need to be directed at a multitude of different strains present throughout the country as well as in individual herds.

J Mol Biol, 2000 Jun 30, 300(1), 141 - 52
Structural and biochemical investigations of the catalytic mechanism of an NADP-dependent aldehyde dehydrogenase from Streptococcus mutans; Cobessi D et al.; The NADP-dependent non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase from Streptococcus mutans (abbreviated Sm-ALDH) belongs to the aldehyde dehydrogenase (ALDH) family . Its catalytic mechanism proceeds via two steps, acylation and deacylation . Its high catalytic efficiency at neutral pH implies prerequisites relative to the chemical mechanism . First, the catalytic Cys284 should be accessible and in a thiolate form at physiological pH to attack efficiently the aldehydic group of the glyceraldehyde-3-phosphate (G3P) . Second, the hydride transfer from the hemithioacetal intermediate toward the nicotinamide ring of NADP should be efficient . Third, the nucleophilic character of the water molecule involved in the deacylation should be strongly increased . Moreover, the different complexes formed during the catalytic process should be stabilised.The crystal structures presented here (an apoenzyme named Apo2 with two sulphate ions bound to the catalytic site, the C284S mutant holoenzyme and the ternary complex composed of the C284S holoenzyme and G3P) together with biochemical results and previously published apo and holo crystal structures (named Apo1 and Holo1, respectively) contribute to the understanding of the ALDH catalytic mechanism.Comparison of Apo1 and Holo1 crystal structures shows a Cys284 side-chain rotation of 110 degrees, upon cofactor binding, which is probably responsible for its pK(a) decrease . In the Apo2 structure, an oxygen atom of a sulphate anion interacts by hydrogen bonds with the NH2 group of a conserved asparagine residue (Asn154 in Sm-ALDH) and the Cys284 NH group . In the ternary complex, the oxygen atom of the aldehydic carbonyl group of the substrate interacts with the Ser284 NH group and the Asn154 NH2 group . A substrate isotope effect on acylation is observed for both the wild-type and the N154A and N154T mutants . The rate of the acylation step strongly decreases for the mutants and becomes limiting . All these results suggest the involvement of Asn154 in an oxyanion hole in order to stabilise the tetrahedral intermediate and likely the other intermediates of the reaction . In the ternary complex, the cofactor conformation is shifted in comparison with its conformation in the C284S holoenzyme structure, likely resulting from its peculiar binding mode to the Rossmann fold (i.e . non-perpendicular to the plane of the beta-sheet) . This change is likely favoured by a characteristic loop of the Rossmann fold, longer in ALDHs than in other dehydrogenases, whose orientation could be constrained by a conserved proline residue . In the ternary and C284S holenzyme structures, as well as in the Apo2 structure, the Glu250 side-chain is situated less than 4 A from Cys284 or Ser284 instead of 7 A in the crystal structure of the wild-type holoenzyme . It is now positioned in a hydrophobic environment . This supports the pK(a) assignment of 7.6 to Glu250 as recently proposed from enzymatic studies .

J Med Assoc Thai, 2000 May, 83(5), 467 - 73
Perivalvular abscesses due to Staphylococcus aureus endocarditis comparison with Streptococcus viridans endocarditis and incremental value of transesophageal echocardiography; Pachirat O et al.; BACKGROUND: Perivalvular abscesses are major complications of infective endocarditis (IE) . The prevalence and best approach to detection of this complication in Staphylococcus aureus (SA) in comparison to Streptococcus viridans (SV) IE is unclear . METHOD: Among 243 consecutive episodes of IE diagnosed using the Duke criteria, who underwent either transthoracic (TTE) or transesophageal echocardiography (TEE) at the Mayo Clinic between 1988 and 1993, there were 64 cases of SV and 61 of SA IE . Comparison of TTE and TEE detection of abscesses were restricted to patients with either surgical or autopsy examination and both TTE and TEE were performed . RESULTS: Prosthetic valve and valve repair were significantly higher in SA compared to SV IE (46 vs 23%, P = 0.008) . The prevalence of abscesses was higher in SA compared to SV IE (42 vs 14%, P = 0.08) . 1 (10%) of abscess detected by TTE in SA compared to 1 (50%) in SV IE and 6 (60%) by TEE in SA and 1 (50%) in SV IE . Incremental value of TEE vs TTE was higher in SA 5/24 (21%) than in SV IE 0/14 (0%) P = 0.067 . Hospital mortality was significantly higher in SA than SV IE (13 vs 2%, P = 0.013) . CONCLUSION: Patients diagnosed with IE and those with SA 1) presented more often with prosthetic valve IE, 2) developed more perivalvular abscesses, and 3) had a higher in hospital mortality than those with SV . Incremental value of TEE was higher in SA than in SV IE, 4) therefore, had a stringent requirement for initial and repeated TEE to detect this ominous complication of IE.

Chin J Dent Res, 1999 May, 2(2), 23 - 6
Immunolabeling of the major cell surface protein antigen of Streptococcus sobrinus with monoclonal antibody; Fan M et al.; OBJECTIVE: The purpose of this study was to determine the accessibility of monoclonal antibody (McAb), specific for the major cell surface protein antigen (PAg) of Streptococcus sobrinus, to the surface of its native epitopes . MATERIALS AND METHODS: An indirect immunogold labeling technique was used to detect the reaction of McAb with S . sobrinus 6715 . The reactions of polyclonal antibodies (PcAbs) against S . sobrinus 6715 or PAg with S . sobrinus 6715, S . mutans Ingbritt C and S . rattus BHT were studied as controls . RESULTS: The results indicated that PAg was localized on the outer cell surface of S . sobrinus, and McAb was reactive with only a few epitopes of the cell surface, whereas PcAbs were found to be reactive with more epitopes . CONCLUSIONS: McAb was specific for the PAg, but there was cross-reaction with S . mutans . Also there seemed to be an association between the fuzzy coat on the surface of S . sobrinus and PAg.

Diagn Microbiol Infect Dis, 2000 Jun, 37(2), 107 - 13
Antimicrobial susceptibilities and serotypes of Streptococcus pneumoniae in southwestern Japan and correlation of penicillin-binding protein 2b and 2x mutations in susceptibilities of penicillin G and cefotaxime; Nagai K et al.; MICs of penicillin G and other drugs and serotypes were determined for 218 strains of Streptococcus pneumoniae isolated from children in southwestern Japan . Twenty-one (9.6%) and 81 (37.2%) isolates were penicillin-resistant (MIC >/=2.0 microg/ml) and intermediate (MIC 0.13-1.0 microg/ml), respectively . Panipenem was most active parenteral agent against penicillin-intermediate (MIC(90) 0.125 microg/ml) and -resistant strains (MIC(90) 0.25 microg/ml) . Among oral beta-lactam agents, cefditoren had good activity against penicillin-intermediate and resistant strains (MIC(90) 0.5/1.0 microg/ml) . Serogroup 6 was the most prevalent (65/218) among all strains and 19F (44 strains) was the most prevalent among penicillin-intermediate and -resistant strains . Both pbp2b resistant and susceptible genes were found in penicillin-intermediate strains . Pbp2x resistant genes were found in 33 of 80 (41.3%) cefotaxime-susceptible strains . These results suggest that possible resistance mechanisms may occur even in drug susceptible strains and that drug susceptibility survey should be updated carefully in Japan.

J Immunol, 2000 Jul 1, 165(1), 419 - 25
Group B Streptococcus induces TNF-alpha gene expression and activation of the transcription factors NF-kappa B and activator protein-1 in human cord blood monocytes; Vallejo JG et al.; It has been postulated that production of TNF-alpha is central to the pathogenesis of septic shock induced by group B Streptococcus (GBS) . In vitro studies using human cord blood monocytes have demonstrated that GBS induces TNF-alpha secretion, but little is known about the intracellular signaling pathways of TNF-alpha induction . In this report we show that heat-killed serotype III GBS induces host cell signal transduction pathways that lead to activation of the transcription factors NF-kappaB and AP-1 . Using adenoviral transfer of IkappaBalpha (IkappaBalpha overexpression), the production of TNF-alpha induced by whole GBS was inhibited by only 20% . We also show that the p38 mitogen-activated protein kinase (MAPK) pathway is involved in GBS-induced TNF-alpha secretion, because TNF-alpha protein and mRNA levels in the presence of a specific inhibitor of p38 MAPK, SB 202190, were dramatically diminished . EMSAs showed that SB 202190 inhibited GBS-induced AP-1 activation, but had no effect on NF-kappaB-DNA binding activity . These results indicate that both NF-kappaB and AP-1 (via p38 MAPK) are involved in the regulation of TNF-alpha production in GBS-stimulated neonatal monocytes . Therefore, disrupting the signal transduction pathways induced by GBS has the potential to attenuate the production of immune response mediators, thereby halting or possibly reversing the course of this potentially fatal disease.

J Mol Biol, 2000 Jun 2, 299(2), 477 - 85
The crystal structure of the penicillin-binding protein 2x from Streptococcus pneumoniae and its acyl-enzyme form: implication in drug resistance; Gordon E et al.; Penicillin-binding proteins (PBPs), the primary targets for beta-lactam antibiotics, are periplasmic membrane-attached proteins responsible for the construction and maintenance of the bacterial cell wall . Bacteria have developed several mechanisms of resistance, one of which is the mutation of the target enzymes to reduce their affinity for beta-lactam antibiotics . Here, we describe the structure of PBP2x from Streptococcus pneumoniae determined to 2.4 A . In addition, we also describe the PBP2x structure in complex with cefuroxime, a therapeutically relevant antibiotic, at 2.8 A . Surprisingly, two antibiotic molecules are observed: one as a covalent complex with the active-site serine residue, and a second one between the C-terminal and the transpeptidase domains . The structure of PBP2x reveals an active site similar to those of the class A beta-lactamases, albeit with an absence of unambiguous deacylation machinery . The structure highlights a few amino acid residues, namely Thr338, Thr550 and Gln552, which are directly related to the resistance phenomenon .

J Mol Biol, 2000 May 26, 299(1), 157 - 68
Conservation and variation in superantigen structure and activity highlighted by the three-dimensional structures of two new superantigens from Streptococcus pyogenes; Arcus VL et al.; Bacterial superantigens (SAgs) are a structurally related group of protein toxins secreted by Staphylococcus aureus and Streptococcus pyogenes . They are implicated in a range of human pathologies associated with bacterial infection whose symptoms result from SAg-mediated stimulation of a large number (2-20%) of T-cells . At the molecular level, bacterial SAgs bind to major histocompatability class II (MHC-II) molecules and disrupt the normal interaction between MHC-II and T-cell receptors (TCRs) . We have determined high-resolution crystal structures of two newly identified streptococcal superantigens, SPE-H and SMEZ-2 . Both structures conform to the generic bacterial superantigen folding pattern, comprising an OB-fold N-terminal domain and a beta-grasp C-terminal domain . SPE-H and SMEZ-2 also display very similar zinc-binding sites on the outer concave surfaces of their C-terminal domains . Structural comparisons with other SAgs identify two structural sub-families . Sub-families are related by conserved core residues and demarcated by variable binding surfaces for MHC-II and TCR . SMEZ-2 is most closely related to the streptococcal SAg SPE-C, and together they constitute one structural sub-family . In contrast, SPE-H appears to be a hybrid whose N-terminal domain is most closely related to the SEB sub-family and whose C-terminal domain is most closely related to the SPE-C/SMEZ-2 sub-family . MHC-II binding for both SPE-H and SMEZ-2 is mediated by the zinc ion at their C-terminal face, whereas the generic N-terminal domain MHC-II binding site found on many SAgs appears not to be present . Structural comparisons provide evidence for variations in TCR binding between SPE-H, SMEZ-2 and other members of the SAg family; the extreme potency of SMEZ-2 (active at 10(-15) g ml-1 levels) is likely to be related to its TCR binding properties . The smez gene shows allelic variation that maps onto a considerable proportion of the protein surface . This allelic variation, coupled with the varied binding modes of SAgs to MHC-II and TCR, highlights the pressure on SAgs to avoid host immune defences.

Kansenshogaku Zasshi, 2000 May, 74(5), 458 - 64
{Retrospective studies of penicillin-resistant pneumococcal acute otitis media in infants and children--epidemiological study}; Uno Y; Retrospective studies of the prognostic factors of infantile acute otitis media caused by Penicillin-resistant Streptococcus pneumoniae were performed . In this study, the following items were discussed the following items; age, sex, presence of nurturance, presence of acute otitis media, presence of sibling, presence of past antibiotic therapy, presence of past therapy for this type of otitis media, MIC of PCG, MIC of CDTR . 1 . Statistically significant results were obtained in the following items; age, presence of acute otitis media, presence of past antibiotic therapy, presence of past therapy of this type of otitis media (especially that treated by an otolaryngologist) . 2 . In previous reports, persistent and recurrent otitis media was influenced by participation in kindergarten groups . However in this study, a statistically significant difference was not recognized . 3 . Statistically significant results were not recognized in the MIC of PCG and the MIC of CDTR for PRSP . 4 . In this study, immunities of each infants were not discussed, but it was necessary for us to examine the factors of immunity in infants, such as specific pneumococcal antigen and type-specific IgG2 antibody and comparison of such titers to the various results of treatment.

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