Streptococci

J Am Acad Dermatol, 2002 Oct, 47(4), 493 - 6
Acute infectious purpura fulminans associated with asplenism or hyposplenism; Ward KM et al.; Acute infectious purpura fulminans is a rapidly progressive syndrome of hemorrhagic skin necrosis associated with acute infection and disseminated intravascular coagulation . We report 5 cases of purpura fulminans and briefly review the literature . All cases were associated with encapsulated organisms (Streptococcus pneumoniae or Group A streptococcus), and 4 of the 5 patients had asplenism or functional hyposplenism.

J Am Acad Dermatol, 2002 Oct, 47(4), 489 - 92
Fulminant group A streptococcal necrotizing fasciitis: clinical and pathologic findings in 7 patients; Dahl PR et al.; BACKGROUND: Necrotizing fasciitis is a rapidly progressive soft tissue infection with high morbidity and mortality rates . Examination of deep incisional biopsy specimens can provide prompt diagnosis and improve survival . We describe 7 patients with necrotizing fasciitis caused by group A Streptococcus species . OBJECTIVE: Our purpose was to describe the unique dermatopathology and clinical features in 7 patients with necrotizing fasciitis caused by group A Streptococcus . METHODS: We conducted a retrospective review . RESULTS: The average age of the patients was 47 years . Fasciitis occurred on an extremity in all cases . All 5 patients with streptococcal toxic shock syndrome died of their disease . The histopathologic findings from early fascial disease revealed superficial epidermal necrosis, edema, and hemorrhage with few inflammatory cells, whereas clinically advanced, necrotic skin lesions revealed diffuse necrosis, thrombosis, neutrophilia, and numerous gram-positive diplococci . CONCLUSIONS: Patients with clinical features of necrotizing fasciitis should have a deep incisional biopsy specimen obtained from the central area of ecchymotic, necrotic plaques to confirm the diagnosis . Immediate surgical intervention is necessary to reduce the morbidity and mortality rates associated with necrotizing fasciitis.

Plant Cell, 1994 Apr, 6(4), 561 - 570
Fructan as a New Carbohydrate Sink in Transgenic Potato Plants; Van Der Meer IM et al.; Fructans are polyfructose molecules that function as nonstructural storage carbohydrates in several plant species that are important crops . We have been studying plants for their ability to synthesize and degrade fructans to determine if this ability is advantageous . We have also been analyzing the ability to synthesize fructan in relation to other nonstructural carbohydrate storage forms like starch . To study this, we induced fructan accumulation in normally non-fructan-storing plants and analyzed the metabolic and physiological properties of such plants . The normally non-fructan-storing potato plant was modified by introducing the microbial fructosyltransferase genes so that it could accumulate fructans . Constructs were created so that the fructosyltransferase genes of either Bacillus subtilis (sacB) or Streptococcus mutans (ftf) were fused to the vacuolar targeting sequence of the yeast carboxypeptidase Y (cpy) gene . These constructs were placed under the control of the constitutive cauliflower mosaic virus 35S promoter and introduced into potato tissue . The regenerated potato plants accumulated high molecular mass (>5 {times} 106 D) fructan molecules in which the degree of polymerization of fructose units exceeded 25,000 . Fructan accumulation was detected in every plant tissue tested . The fructan content in the transgenic potato plants tested varied between 1 and 30% of dry weight in leaves and 1 and 7% of dry weight in microtubers . Total nonstructural neutral carbohydrate content in leaves of soil-grown plants increased dramatically from 7% in the wild type to 35% in transgenic plants . Our results demonstrated that potato plants can be manipulated to store a foreign carbohydrate by introducing bacterial fructosyltransferase genes . This modification affected photosynthate partitioning in microtubers and leaves and increased nonstructural carbohydrate content in leaves.

J Med Liban, 2001 Sep-Oct, 49(5), 246 - 56
Antibiotic resistance and the need for the rational use of antibiotics; Hueston WJ et al.; Antibiotic resistance has increased dramatically over the past 10 years . In many countries, penicillin resistance to Streptococcus pneumoniae is nearly 50% with resistance to other drugs rising as well . One of the mechanisms responsible for the development of resistance is the widespread use of antibiotics in the primary care setting, chiefly for the treatment of respiratory disorders . Reduction in antibiotic prescribing for respiratory diseases in primary care has been associated with decreases in drug resistance in Streptococcus pneumoniae . This article will review common reasons for overuse of antibiotics in primary care settings and some strategies for reducing injudicious antibiotic prescribing.

Int J Pediatr Otorhinolaryngol, 2002 Sep 24, 65(3), 203 - 11
Analysis by cDNA microarrays of altered gene expression in middle ears of rats following pneumococcal infection; Lin J et al.; Objective: Streptococcus pneumoniae is the most common pathogen in otitis media . Infection of the middle ear with S . pneumoniae potentiates development of thick effusion in the middle ear which frequently causes hearing loss and communication disorders in children . What has changed immediately in the middle ear cleft following pneumococcal infection is extensively studied and characterized but what has changed ever after remains elusive . The purpose of this study is to explore the cellular and molecular basis that remains on a longer time after acute pneucmococcal middle ear infection and potentiates development of thick effusion in the middle ear . METHODS: 12 rats were intrabullarly inoculated with pneumococcus at 2.5x10(6) CFU/ear and profiles of gene expression in the middle ear were examined by cDNA microarrays in combination with reverse transcription-polymer chain reaction (RT-PCR) 6 weeks after infection while the morphologic changes in middle ear were simultaneously characterized by histopathologic techniques . Twelve rats receiving phosphate-buffered saline (PBS) served as controls . RESULTS: it demonstrated that pneumococcus infected ears had the expression of the following genes at a high level compared to the controls: mitogenic signaling proteins (mitogen-activated protein kinase {MEK1 and MEK2}, helix-loop-helix transcriptional regulators (Id3 and Id1), ion channels (sodium channel beta 1 and sodium channel 2), and mucin glycoproteins (Muc2 and Muc5) . The morphology demonstrated a thickened mucosa and submucosa with increased expression of macroglycoconjugates compared to the controls . CONCLUSION: the expression of several genes remains high even after the acute episode of pneumococcal otitis media has been resolved . The up-regulated expression of these genes may serve as the basis for the development of thick effusion and mucous cell metaplasia/hyperplasia once it is complicated with other factors such as dysfunction of the Eustachian tube.

J Antimicrob Chemother, 2002 Sep, 50 Suppl S1, 39 - 47
Molecular characterization of macrolide resistance mechanisms among Streptococcus pneumoniae and Streptococcus pyogenes isolated from the PROTEKT 1999-2000 study; Farrell DJ et al.; In this study, the distribution of macrolide resistance mechanisms was determined for isolates of Streptococcus pneumoniae and Streptococcus pyogenes obtained from the PROTEKT 1999-2000 study (a global, longitudinal study of the antibacterial susceptibility of bacterial pathogens associated with community-acquired lower respiratory tract infections) . The global macrolide resistance mechanism distribution results for 1043 macrolide-resistant S . pneumoniae isolates collected from 25 countries were as follows: 35.3% mef(A), 56.2% erm(B), 6.8% both mef(A) and erm(B), 0.2% erm(A) subclass erm(TR) and 1.5% negative for mechanisms tested . Mechanisms of macrolide resistance were found to vary widely between countries and different geographical regions with mef(A) predominating in North America and erm(B) in Europe . Approximation of genotype from macrolide MIC without molecular determination of the mechanism of resistance resulted in an error of 10.2% (106 isolates) . Overall, for 143 macrolide-resistant S . pyogenes isolates, 46.1% of the isolates tested were mef(A), 30.8% were erm(B), 23.1% were erm(A) subclass erm(TR) and no isolates were negative for all the genetic markers tested . Again, the distribution varied widely between countries and geographical regions . This study provides valuable baseline data for the continued monitoring of the evolution of macrolide resistance development in these important respiratory tract pathogens . The ketolide telithromycin retained excellent anti-pneumococcal activity irrespective of macrolide resistance mechanism, having a MIC(90) of 0.25, 0.5 and 0.5 mg/L against mef(A), erm(B) and mef(A)+erm(B) macrolide-resistant S . pneumoniae, respectively . It also exhibited potent activity against S . pyogenes that had become resistant to macrolides via either mef(A), (MIC(90 )0.5 mg/L) or erm(TR), (MIC(90) 0.03 mg/L).

J Antimicrob Chemother, 2002 Sep, 50 Suppl S1, 25 - 37
Increasing prevalence of antimicrobial resistance among isolates of Streptococcus pneumoniae from the PROTEKT surveillance study, and compatative in vitro activity of the ketolide, telithromycin; Felmingham D et al.; The prevalence of resistance to a range of antimicrobials was determined for isolates of Streptococcus pneumoniae examined in the PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) surveillance study (1999-2000) using NCCLS testing methods and interpretative criteria . Of 3362 pneumococcal isolates collected from 69 centres in 25 countries, 22.1% overall were resistant to penicillin G, with the highest rates of resistance found among isolates from Asia (53.4%), France (46.2%) and Spain (42.1%) . Erythromycin A resistance occurred in 31.1% of isolates overall with the highest rates found in Asia (79.6%), France (57.6%), Hungary (55.6%) and Italy (42.9%) . Marked geographical differences in the prevalence of both penicillin G (the Netherlands 0%; South Korea 71.5%) and erythromycin A (Sweden 4.7%; South Korea 87.6%) resistance were observed . Asia was characterized by the highest prevalence of resistance, overall, with only eight of 19 antimicrobials (co-amoxiclav, linezolid, vancomycin, teicoplanin, quinupristin/dalfopristin, levofloxacin, moxifloxacin and telithromycin) retaining high activity against isolates of S . pneumoniae from this region . Notable rates of resistance to clarithromycin, azithromycin, co-trimoxazole and tetracycline were observed in the majority of countries submitting isolates of S . pneumoniae to the PROTEKT surveillance study . Fluoroquinolone resistance was low (1%), overall, although 14.3% of 70 isolates from Hong Kong were resistant to levofloxacin and moxifloxacin, all but one of these isolates belonging to a single clone of the 23F serotype . Although, at present, apparently limited to pockets of clonal spread, continued vigilance with regard to the evolution of fluoroquinolone resistance is indicated . Telithromycin (MIC(90) 0.12 mg/L; 99.9% of isolates susceptible) and lin- ezolid (MIC(90) 2 mg/L; 100% of isolates susceptible) were the two most active oral agents tested, both compounds retaining activity against isolates of fluoroquinolone-resistant S . pneumoniae . The results of the PROTEKT surveillance study 1999-2000 emphasize the widespread evolution of resistance to a variety of antimicrobials amongst isolates of S . pneumoniae and demonstrate the potential of telithromycin as a therapeutic option for the treatment of community-acquired respiratory tract infections caused by this organism.

J Antimicrob Chemother, 2002 Sep, 50 Suppl S1, 9 - 24
Antimicrobial resistance amongst isolates of Streptococcus pyogenes and Staphylococcus aureus in the PROTEKT antimicrobial surveillance programme during 1999-2000; Canton R et al.; The pattern of susceptibility to a range of antimicrobials was tested for 1485 isolates of Streptococcus pyogenes and 1547 isolates of Staphylococcus aureus included in the international PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) surveillance study (1999-2000) . Overall, almost 10% of S . pyogenes isolates were erythromycin A resistant . There was a wide heterogeneity of resistance, with high levels of macrolide resistance in Poland (42%), Hong Kong (28%), Italy (25%), Portugal (24%) and Spain (21%), and no macrolide resistance in Indonesia, Austria, Belgium, the Netherlands or the UK . Using NCCLS tentative breakpoints, 97.6% of isolates were susceptible to telithromycin, with MIC(90) < or = 0.015 mg/L in most regions . Resistance among S . pyogenes to the beta-lactams (MIC(90) < or = 0.12 mg/L for all except cefaclor) and fluoroquinolones was not detected . Macrolide resistance was present among the S . aureus isolates, and as with S . pyogenes, there was a wide heterogeneity of resistance, with lower rates in Australia, Indonesia, Hungary, Austria, Germany, the Netherlands, Portugal, Sweden and Switzerland . Methicillin-resistant isolates were resistant to the beta-lactams and the macrolides . Resistance to telithromycin was detected in methicillin-resistant isolates in Latin and North America, Asia and Europe . Telithromycin resistance was non-existent or low (MIC(90 )range 0.06-0.25 mg/L) in Australia, Indonesia, Hungary, Austria, Germany, the Netherlands, Portugal, Sweden and Switzerland . Regardless of methicillin susceptibility, resistance to linezolid, teicoplanin or vancomycin was not apparent globally.

J Med Chem, 2002 Sep 26, 45(20), 4559 - 70
4-Substituted D-glutamic acid analogues: the first potent inhibitors of glutamate racemase (MurI) enzyme with antibacterial activity; de Dios A et al.; The first potent inhibitors of glutamate racemase (MurI) enzyme that show whole cell antibacterial activity are described . Optically pure 4-substituted D-glutamic acid analogues with (2R,4S) stereochemistry and bearing aryl-, heteroaryl-, cinnamyl-, or biaryl-methyl substituents represent a novel class of glutamate racemase inhibitors . Exploration of the D-Glu core led to the identification of lead compounds (-)-8 and 10 . 2-Naphthylmethyl derivative 10 was found to be a potent competitive inhibitor of glutamate racemase activity (K(i) = 16 nM, circular dichroism assay; IC(50) = 0.1 microg/mL high-performance liquid chromatography (HPLC) assay) . Thorough structure-activity relationship (SAR) studies led to benzothienyl derivatives such as 69 and 74 with increased potency (IC(50) = 0.036 and 0.01 microg/mL, respectively, HPLC assay) . These compounds showed potent whole cell antibacterial activity against S . pneumoniae PN-R6, and good correlation with the enzyme assay . Compounds 69, 74 and biaryl derivative 52 showed efficacy in an in vivo murine thigh infection model against Streptococcus pneumoniae . Data described herein suggest that glutamate racemase may be a viable target for developing new antibacterial agents.

J Laryngol Otol, 2002 Jul, 116(7), 541 - 2
Group-A streptococcal meningitis in an adult, secondary to purulent otitis media; Cohen-Kerem R et al.; Group A streptococcal meningitis is rarely encountered today, although group A streptococcal severe infections are on the increase . We present here a case of an adult male with bacterial meningitis as a complication of otitis media induced by Group A Streptococcus . The approach to diagnosis and treatment considerations are discussed.

J Wildl Dis, 2002 Jul, 38(3), 641 - 3
Streptococcus equisimilis infection in striped skunks (Mephitis mephitis) in Saskatchewan; Hwang YT et al.; Three radio-collared striped skunks (Mephitis mephitis) found dead during a field study of winter ecology of striped skunks near Willowbrook, Saskatchewan, Canada were examined . Streptococcus equisimilis was identified as the primary agent causing necrotizing purulent pneumonia in one skunk and suppurative meningoencephalitis in another . Both Streptococcus equisimilis and Streptococcus canis were isolated from lesions of purulent myocarditis and pyothorax in the third skunk . These are apparently the first reported cases of S . equisimilis infection in striped skunks and suggest that this opportunistic pathogen may be a significant cause of mortality under some conditions.

Pediatr Infect Dis J, 2002 Jul, 21(7), 642 - 7
Dynamics of pneumococcal nasopharyngeal carriage in children with nonresponsive acute otitis media treated with two regimens of intramuscular ceftriaxone; Haiman T et al.; BACKGROUND: A 3-day intramuscular ceftriaxone regimen was superior to a 1-day regimen in the treatment of nonresponsive acute otitis media caused by resistant Streptococcus pneumoniae . However, the effect of various regimens of intramuscular cefriaxone on the nasopharyngeal carriage of S . pneumoniae and especially that of resistant strains during and after therapy has not been thoughtfully studied . OBJECTIVES: To compare the effect of one dose and three dose intramuscular ceftriaxone regimens on the nasopharyngeal carriage of S . pneumoniae in patients with nonresponsive acute otitis media treated with these two regimens and to document the dynamics of nasopharyngeal colonization with S . pneumoniae during and after completion of these two therapeutic regimens . PATIENTS AND METHODS: In a prospective study performed during January, 1998, through September, 1999, 170 evaluable patients ages 3 to 36 months with nonresponsive acute otitis media were randomized to receive the 1 (n = 83)- or 3 (n = 87)-day intramuscular ceftriaxone regimen (50 mg/kg/day), respectively . Nasopharyngeal cultures for S . pneumoniae were obtained on Days 1, 4 to 5, 11 to 14 and 28 to 30 . Susceptibility of S . pneumoniae to penicillin and ceftriaxone was determined by E-test . RESULTS: On Day 1 nasopharyngeal S . pneumoniae carriage was found in 108 (64%) patients, 54 in each treatment group . Forty-seven of 54 (87%) and 9 of 54 (17%) S . pneumoniae isolates from the one dose group were nonsusceptible to penicillin and ceftriaxone, respectively; the respective values in the three dose group were 49 of 54 (91%) and 8 of 54 (15%) . On Days 4 and 5 negative nasopharyngeal cultures were achieved in 43 of 83 (52%) and 70 of 87 (80%) cases from the one dose and three dose group, respectively (P < 0.001) . Eradication of penicillin-nonsusceptible S . pneumoniae was achieved on Day 4 to 5 in 18 of 49 (37%) and 39 of 49 (80%) organisms isolated from the one dose and three dose groups, respectively (P < 0.001) . Nasopharyngeal S . pneumoniae carriage among evaluable patients on Days 11 to 14 and Days 28 to 30 was 43 of 69 (62%) and 31 of 45 (69%) for the one dose group and 42 of 73 (58%) and 31 of 50 (62%) for the three dose group, respectively (P not significant) . A decrease was observed during the study period in the proportion of highly penicillin-resistant S . pneumoniae isolated in the three dose group compared with the one dose group (30, 24, 17 and 13% vs . 30, 27, 19 and 26% at Days 1, 4 to 5, 11 to 14 and 28 to 30, respectively; P = 0.05) . CONCLUSIONS: A marked reduction in the carriage of penicillin-nonsusceptible S . pneumoniae (including highly penicillin-resistant organisms) was achieved on Days 4 to 5 of therapy with both ceftriaxone regimens . The 3-day intramuscular ceftriaxone regimen was significantly superior to the 1-day regimen in the reduction of carriage during the treatment period . The reduction of overall S . pneumoniae nasopharyngeal carriage by both ceftriaxone regimens was a short-lived phenomenon followed by rapid recolonization of the nasopharynx.

J Biol Chem, 2002 Nov 22, 277(47), 44809 - 16 Epub 2002 Sep 16.
A new mechanism for anaerobic unsaturated fatty acid formation in Streptococcus pneumoniae; Marrakchi H et al.; The anaerobic pathway for unsaturated fatty acid synthesis was established in the 1960s in Escherichia coli . The double bond is introduced into the growing acyl chain by FabA, an enzyme capable of both the dehydration of beta-hydroxydecanoyl-acyl carrier protein (ACP) to trans-2-decenoyl-ACP, and the isomerization of trans-2 to cis-3-decenoyl-ACP . However, there are a number of anaerobic bacteria whose genomes do not contain a fabA homolog, although these organisms nonetheless produce unsaturated fatty acids . We cloned and biochemically characterized a new enzyme in type II fatty acid synthesis from Streptococcus pneumoniae that carries out the isomerization of trans-2-decenoyl-ACP to cis-3-decenoyl-ACP, but is not capable of catalyzing the dehydration of beta-hydroxy intermediates . This tetrameric enzyme, designated FabM, has no similarity to FabA, but rather is a member of the hydratase/isomerase superfamily . Thus, the branch point in the biosynthesis of unsaturated fatty acids in S . pneumoniae occurs following the formation of trans-2-decenoyl-ACP, in contrast to E . coli where the branch point takes place after the formation of beta-hydroxydecanoyl-ACP.

Rev Neurol, 2002 Aug 16-31, 35(4), 331 - 6
{Subdural empyema secondary to sinusitis: four pediatric cases}; Oliveira-Monteiro JP et al.; INTRODUCTION: Perinasal sinus infections is a common and benign condition in most pediatric cases . Because of the widespread use of antibiotics, intracranial extension of sinusitis is rarely seen today . Nevertheless, the clinician must be aware of the gravity of this condition, because late recognition and delay in treatment can increase mortality and morbidity . The authors made a retrospective study of pediatric patients admitted to Garcia de Orta Hospital between 1996 and 2001 with the diagnosis of subdural empyema and sinusitis . CASE REPORTS: Four patients were identified, with ages between 9 and 13 years . Prodromal manifestations of sinusitis were present in all, followed several days later by headaches, fever, vomiting and neurological abnormalities . Two patients presented in the emergency department with an acute confusional state and a non convulsive status epilepticus . The other two patients had a longer duration of disease, severe deterioration of consciousness and focal neurologic signs . Medical treatment was started in all cases at admission, but none improved significantly before being submitted to surgical intervention, which was repeated several times in two patients . Streptococcus milleri and anaerobic organisms were isolated . There was no mortality and global evolution was favorable, with a median follow up of 32 months . CONCLUSIONS: Clinical presentation of subdural empyema can be relatively inespecific, requiring a high degree of suspicion . Facing a young adolescent with fever of unknown origin associated with any neurological abnormality and previous history of sinusitis, neuroradiological investigation shoul be asked . Early diagnosis and treatment are the mainstays of successful outcome.

J Biol Chem, 2002 Dec 27, 277(52), 50654 - 9 Epub 2002 Sep 13.
Crystal structure of Tritrichomonas foetus inosine monophosphate dehydrogenase in complex with the inhibitor ribavirin monophosphate reveals a catalysis-dependent ion-binding site; Prosise GL et al.; Inosine monophosphate dehydrogenase (IMPDH) catalyzes the rate-limiting step in GMP biosynthesis . The resulting intracellular pool of guanine nucleotides is of great importance to all cells for use in DNA and RNA synthesis, metabolism, and signal transduction . The enzyme binds IMP and the cofactor NAD(+) in random order, IMP is converted to XMP, NAD(+) is reduced to NADH, and finally, NADH and then XMP are released sequentially . XMP is subsequently converted into GMP by GMP synthetase . Drugs that decrease GMP synthesis by inhibiting IMPDH have been shown to have antiproliferative as well as antiviral activity . Several drugs are in use that target the substrate- or cofactor-binding site; however, due to differences between the mammalian and microbial isoforms, most drugs are far less effective against the microbial form of the enzyme than the mammalian form . The high resolution crystal structures of the protozoan parasite Tritrichomonas foetus IMPDH complexed with the inhibitor ribavirin monophosphate as well as monophosphate together with a second inhibitor, mycophenolic acid, are presented here . These structures reveal an active site cation identified previously only in the Chinese hamster IMPDH structure with covalently bound IMP . This cation was not found previously in apo IMPDH, IMPDH in complex with XMP, or covalently bound inhibitor, indicating that the cation-binding site may be catalysis-dependent . A comparison of T . foetus IMPDH with the Chinese hamster and Streptococcus pyogenes structures reveals differences in the active site loop architecture, which contributes to differences in cation binding during the catalytic sequence and the kinetic rates between bacterial, protozoan, and mammalian enzymes . Exploitation of these differences may lead to novel inhibitors, which favor the microbial form of the enzyme.

Antimicrob Agents Chemother, 2002 Oct, 46(10), 3311 - 5
Fluoroquinolone-resistant Streptococcus pneumoniae strains occur frequently in elderly patients in Japan; Yokota S et al.; We identified and genetically characterized seven fluoroquinolone-resistant Streptococcus pneumoniae strains among 293 clinical strains isolated from 1999 to 2001 in Japan . The resistant strains were isolated only from adults, and 7 of 31 isolates (22.6%) were from patients more than 20 years old . Resistant strains were not found in 262 isolates from children under age 10.

Antimicrob Agents Chemother, 2002 Oct, 46(10), 3261 - 4
Penicillin-binding protein 1A, 2B, and 2X alterations in Canadian isolates of penicillin-resistant Streptococcus pneumoniae; Nichol KA et al.; Alterations within the penicillin-binding domain of penicillin-binding protein (PBP) genes pbp1a, pbp2b, and pbp2x were determined for 15 Canadian isolates of Streptococcus pneumoniae . All penicillin-nonsusceptible S . pneumoniae isolates showed a variety of PBP 2X substitutions and contained a Thr445-Ala change after the PBP 2B SSN motif . Only isolates for which penicillin MICs were > or =0.5 micro g/ml had PBP 1A alterations near the STMK and SRN motifs . Sequence analysis revealed identical PBP 1A, PBP 2B, and PBP 2X substitution patterns among all isolates for which penicillin MICs were > or =1 micro g/ml.

Antimicrob Agents Chemother, 2002 Oct, 46(10), 3185 - 92
Bactericidal effect and pharmacodynamics of cethromycin (ABT-773) in a murine pneumococcal pneumonia model; Kim MK et al.; Cethromycin (ABT-773), a new ketolide, possesses potent in vitro activity against Streptococcus pneumoniae . The objective of this study was to investigate the in vivo bactericidal activity of cethromycin against macrolide-susceptible and -resistant S . pneumoniae in a murine pneumonia model and to describe the pharmacodynamic (PD) profile of cethromycin . Eight (two macrolide susceptible, six macrolide resistant) clinical isolates of S . pneumoniae were investigated . Cyclophosphamide administration rendered ICR mice transiently neutropenic prior to intratracheal inoculation with 0.05 ml of an S . pneumoniae suspension containing 10(7) to 10(8) CFU/ml . Oral cethromycin was initiated 12 to 14 h postinoculation over a dosage range of 0.1 to 800 mg/kg of body weight/day . Lungs from seven to eight mice per treatment and control groups were collected at 0 and 24 h posttherapy to assess bacterial density . The cumulative mortality (n = 12 to 13) was assessed at 120 h (end of therapy) and at 192 h (3 days posttherapy) . Recovery of pneumococci from the lungs of infected animals prior to the initiation of therapy ranged from 4.6 to 7.2 log(10) CFU . Growth in untreated control animals over a 24-h study period increased 0.3 to 2.7 log(10) CFU . Cethromycin demonstrated a substantial bactericidal effect, regardless of macrolide susceptibility . Correlation between changes in bacterial density (24 h) and survival over both 120 and 192 h were statistically significant . All three PD parameters demonstrated a significant correlation with changes in log(10) CFU/lung (Spearman's correlation coefficient, P < 0.001); however, the goodness of fit as assessed with the maximum effect (E(max)) model revealed that the maximum concentration of free drug in serum (C(max free))/MIC and the area under the free drug concentration-time curve (AUC(free))/MIC best explained the relationship between drug exposure and reductions in viable bacterial counts . These data reveal that an approximate cethromycin AUC(free)/MIC of 50 or C(max free)/MIC of 1 results in bacteriostatic effects, while higher values (twofold) maximize survival.

J Appl Microbiol, 2002, 93(4), 631 - 9
Isolation and characterization of a mutant strain of Streptococcus uberis, which fails to utilize a plasmin derived beta-casein peptide for the acquisition of methionine; Smith AJ et al.; AIMS: To isolate and characterize a mutant of Streptococcus uberis strain 0140J which fails to utilize a plasmin derived beta-casein peptide for the acquisition of methionine . METHODS AND RESULTS: Random insertional mutagenesis was used to isolate a mutant strain of Strep . uberis 0140J which was unable to utilize methionine from within a casein-derived peptide . The altered gene in the mutant strain showed homology to an oligopeptide permease gene of Streptococcus pyogenes (oppF) . The mutant was unable to obtain specific amino acids from defined peptides of various lengths and its growth yield in skimmed milk was between 1 and 10% that of the wild-type strain, but was restored following the inclusion of these amino acids . CONCLUSIONS: The oligopeptide permease homologue of Strep . uberis 0140J is necessary for the utilization of amino acids from within specific peptides . Efficient acquisition of essential amino acids by Strep . uberis 0140J is required for the bacterium to achieve an optimum yield in milk . SIGNIFICANCE AND IMPACT OF THE STUDY: Streptococcus uberis is a major agent of bovine mastitis with a corresponding high economic loss . By targeting metabolic pathways essential to the growth of Strep . uberis it may be possible to prevent the establishment of growth of the bacterium in milk . This study has identified the acquisition of essential amino acids as playing a role in the growth of Strep . uberis in milk.

J Infect Dis, 2002 Oct 1, 186(7), 966 - 75 Epub 2002 Sep 09.
Diversity of penicillin-nonsusceptible Streptococcus pneumoniae circulating in Iceland after the introduction of penicillin-resistant clone Spain(6B)-2; Sa-Leao R et al.; After the introduction and extensive dissemination of the multidrug-resistant Streptococcus pneumoniae clone Spain(6B)-2 between 1989 and the early to mid-1990s, the prevalence of pneumococcal isolates expressing intermediate resistance to penicillin, mainly of capsular types 6, 19, and 23, also began to increase in Iceland . The purpose of this study was to investigate whether these isolates originated in Iceland or represented strains imported to the country . Isolates were characterized by pulsed-field gel electrophoresis; multilocus sequence typing; determination of pbp1a, pbp2b, and pbp2x gene restriction patterns; and partial sequencing of these pbp genes . The results indicate that, although singular events suggesting horizontal transfer of pbp genes (and capsular genes) were detected, the majority of clones circulating in the country had genetic backgrounds also detected abroad . The major mechanism of dissemination of penicillin resistance in Iceland appears to be the repeated introduction of multiple lineages, followed by clonal spread.

Curr Microbiol, 2002 Nov, 45(5), 328 - 33
Telithromycin inhibition of protein synthesis and 50S ribosomal subunit formation in Streptococcus pneumoniae cells; Champney WS et al.; The new ketolide antibiotic telithromycin (HMR3647) has been examined for inhibitory effects in cells of Streptococcus pneumoniae . The antibiotic caused a proportional decline in cell growth rate and viability with an IC(50) of 15 ng/ml . At a concentration of 7.5 ng/ml, protein synthesis in these cells was reduced by 50% . As seen in other organisms, this compound was also a very effective inhibitor of the formation of the 50S ribosomal subunit in growing cells . Pulse and chase labeling assays defined the reduced rate of 50S synthesis in antibiotic treated cells . At 7.5 ng/ml the rate was reduced to 50% of the control synthesis rate . An IC(50) of 15 ng/ml was found for the effect on this process . 30S ribosomal subunit formation was unaffected by the antibiotic . Inhibition of translation and 50S particle formation are equivalent targets for this antibiotic . The effects of telithromycin in S . pneumoniae are compared with those found in Staphylococcus aureus cells.

Ugeskr Laeger, 2002 Aug 26, 164(35), 4052 - 5
{Diagnosis and treatment in general practice of lower respiratory tract infections in adults}; Hansen JG et al.; Lower respiratory tract infections are common in the community . It might be difficult to differentiate between acute bronchitis, exacerbation of chronic obstructive pulmonary disease, and pneumonia . There is no satisfactory way of defining pneumonia by clinical criteria alone . Measurement of C-reactive protein is useful, but the specificity of the test is low, and must be carefully evaluated in comparison with the duration of illness and the clinical picture . The antibiotic management of lower respiratory tract infections must suppress Streptococcus pneumoniae . We therefore recommend that the first drug of choice should be penicillin V.

Infect Immun, 2002 Oct, 70(10), 5730 - 9
Identification of a streptolysin S-associated gene cluster and its role in the pathogenesis of Streptococcus iniae disease; Fuller JD et al.; Streptococcus iniae causes meningoencephalitis and death in cultured fish species and soft-tissue infection in humans . We recently reported that S . iniae is responsible for local tissue necrosis and bacteremia in a murine subcutaneous infection model . The ability to cause bacteremia in this model is associated with a genetic profile unique to strains responsible for disease in fish and humans (J . D . Fuller, D . J . Bast, V . Nizet, D . E . Low, and J . C . S . de Azavedo, Infect . Immun . 69:1994-2000, 2001) . S . iniae produces a cytolysin that confers a hemolytic phenotype on blood agar media . In this study, we characterized the genomic region responsible for S . iniae cytolysin production and assessed its contribution to virulence . Transposon (Tn917) mutant libraries of commensal and disease-associated S . iniae strains were generated and screened for loss of hemolytic activity . Analysis of two nonhemolytic mutants identified a chromosomal locus comprising 9 genes with 73% homology to the group A streptococcus (GAS) sag operon for streptolysin S (SLS) biosynthesis . Confirmation that the S . iniae cytolysin is a functional homologue of SLS was achieved by PCR ligation mutagenesis, complementation of an SLS-negative GAS mutant, and use of the SLS inhibitor trypan blue . SLS-negative sagB mutants were compared to their wild-type S . iniae parent strains in the murine model and in human whole-blood killing assays . These studies demonstrated that S . iniae SLS expression is required for local tissue necrosis but does not contribute to the establishment of bacteremia or to resistance to phagocytic clearance.

Infect Immun, 2002 Oct, 70(10), 5706 - 14
The divergently transcribed Streptococcus parasanguis virulence-associated fimA operon encoding an Mn(2+)-responsive metal transporter and pepO encoding a zinc metallopeptidase are not coordinately regulated; Oetjen J et al.; The study of how bacteria respond to and obtain divalent metal ions provides insight into the regulation of virulence factors in the host environment . Regulation of metal permease operons in gram-positive bacteria may involve the binding of metal-responsive repressors to palindromic domains in their control regions . The Streptococcus parasanguis fimA operon, which encodes an ATP-binding cassette (ABC) transporter system with sequence homology to the LraI family of metal transporters, possesses a palindromic regulatory region with high homology to that of the Streptococcus gordonii ScaR binding domain . Mapping of the promoter and regulatory regions of fimA and the divergently transcribed pepO gene, which encodes a zinc metalloendopeptidase, indicated that their promoter and regulatory elements overlap . fimA had one transcriptional start site, whereas pepO had three . Analysis of truncated versions of the pepO promoter suggested that all three transcriptional start sites are functional . Analysis of promoter activity under various environmental conditions indicated that the fimA operon promoter and the pepO promoter are not coordinately regulated . The fimA operon is responsive to changes in Mn(2+) concentration, but the pepO promoter is not . A S . parasanguis fimA mutant showed a growth deficiency under conditions of limiting Mn(2+) . This deficiency was not alleviated by compensation with either Mg(2+) or Fe(3+) . Wild-type S . parasanguis could take up Mn(2+) and Fe(3+), while the fimA mutant showed a marked reduction in this ability . These data suggested that FimA is a component of a metal transporter system capable of transporting both Mn(2+) and Fe(3+) . FimA expression itself was shown to be responsive to Mn(2+) concentration, but not to availability of Fe(3+) or Mg(2+).

Infect Immun, 2002 Oct, 70(10), 5604 - 11
The human complement regulator factor H binds pneumococcal surface protein PspC via short consensus repeats 13 to 15; Duthy TG et al.; The innate ability of Streptococcus pneumoniae to resist complement activation and complement-mediated phagocytosis may be a direct consequence of the ability of the bacteria to bind components of the complement regulatory system . One such component, factor H (fH), is a crucial fluid-phase negative regulator of the alternative pathway of complement and is utilized by a number of pathogenic organisms to resist complement attack . The pneumococcal surface protein C (PspC {also known as CbpA} and SpsA) has been shown to bind fH, although the exact binding site within one or more of the 20 short consensus repeats (SCRs) of the molecule is not known . The purpose of the current study was to map specific SCRs on fH responsible for this binding . Initial experiments utilizing type 2 pneumococcal strain D39 and its isogenic PspC-negative derivative (D39/pspC mutant) showed that fH binding was PspC dependent . A purified recombinant protein derivative of PspC that lacked the proline-rich region (PspCDeltaPro) had a reduced binding efficiency for fH, thereby directly showing the importance of this region for the fH interaction . We have specifically shown by inhibition experiments that SCRs responsible for heparin and C3b binding of fH are not involved in binding PspC and the interaction between fH and PspC is largely hydrophobic, since no inhibition was observed in the presence of high concentrations of NaCl . Construction of SCR proteins encompassing the whole fH molecule showed that SCRs 8 to 15 (SCR 8-15) mediated binding to PspC . Further localization experiments revealed that SCR 13 and SCR 15 were required for full binding, although partial binding was retained when either SCR was removed.

Infect Immun, 2002 Oct, 70(10), 5589 - 95
Enhanced immunogenicity of pneumococcal surface adhesin A by genetic fusion to cytokines and evaluation of protective immunity in mice; Gor DO et al.; Immunization of mice with pneumococcal surface adhesin A (PsaA) emulsified in complete Freund's adjuvant (CFA) provides protection against systemic infection with Streptococcus pneumoniae . Because the use of CFA is not acceptable in humans, we sought to develop alternative means of enhancing the immunogenicity of protein antigens of potential use in pneumococcal vaccines . We designed a series of genetic constructs in which coding sequences for PsaA were linked to sequences encoding either murine interleukin-2 (mIL-2), mIL-4, or two copies of an immunostimulatory nonapeptide derived from mIL-1beta . The PsaA-cytokine constructs were cloned and expressed in Escherichia coli . Mice immunized twice with PsaA-IL-2, or PsaA-IL-4 responded with PsaA-specific antibody production comparable in magnitude to that of mice primed with PsaA in CFA and boosted with PsaA in incomplete Freund's adjuvant (PsaA-Adj) . Antibodies elicited by PsaA-Adj were predominantly of the immunoglobulin G1 (IgG1) subclass, while PsaA-IL-2 and PsaA-IL-4 elicited substantial amounts of IgG2a in addition to IgG1 . Mice immunized with PsaA-Adj or PsaA-IL-4 were partially protected against intraperitoneal challenge with virulent S . pneumoniae (30% overall survival beyond 15 days postchallenge) . Mice immunized with PsaA and no adjuvant or PsaA-IL-2 exhibited 0 or 5% survival rates, respectively, following challenge . In contrast, mice immunized twice with capsular polysaccharide were 100% protected . The modest levels of protection seen in mice immunized with PsaA and its more immunogenic derivatives may be explained in part by the relative inaccessibility of antibody to PsaA on the surface of encapsulated S . pneumoniae.

Infect Immun, 2002 Oct, 70(10), 5454 - 61
Role of RegM, a homologue of the catabolite repressor protein CcpA, in the virulence of Streptococcus pneumoniae; Giammarinaro P et al.; As part of a study of virulence gene regulation in Streptococcus pneumoniae, we have identified a gene encoding a homologue of the staphylococcal catabolite control protein CcpA in the pneumococcal genome sequence . The pneumococcal protein, designated RegM, has significant similarity to members of the LacI/GalR family of bacterial regulatory proteins . S . pneumoniae D39 derivatives with insertion-duplication or deletion mutations in regM were significantly attenuated in virulence with respect to the wild-type strain . In defined media containing either sucrose or lactose as sole carbon sources, the in vitro growth rates of D39 and the regM mutants were essentially the same . However, in the presence of galactose the regM mutants grew significantly faster than the wild-type strain, whereas growth rates were significantly lower in the presence of glucose or maltose . These data are consistent with the involvement of regM in the catabolism of carbohydrates in S . pneumoniae . RegM was a repressor of both alpha-glucosidase and beta-galactosidase activities in S . pneumoniae, but unlike the situation in certain other bacteria, it does not mediate the repression of these enzymes by glucose . The observed attenuation in virulence was not attributable to poorer growth of the regM mutants in mouse blood ex vivo, but nevertheless, the mutants were rapidly cleared from the blood of infected mice in vivo . The regM mutation had no apparent impact on expression of several confirmed pneumococcal virulence proteins, but studies employing a lacZ transcriptional fusion construct indicated that mutation of regM resulted in a significant reduction in transcription of the capsular polysaccharide biosynthesis locus (cps) . Thus, regM is the first gene outside of the cps locus to be implicated in regulation of capsular gene expression.

Semin Respir Infect, 2002 Sep, 17(3), 204 - 14
Clinical relevance of penicillin-resistant Streptococcus pneumoniae; Cunha BA; Streptococcus pneumoniae is the most important respiratory tract pathogen in otitis, sinusitis, bronchitis, and community-acquired pneumonia . Over the past decades, there has been an increase in minimum inhibitory concentrations (MICs) to penicillin . Decreased susceptibility to penicillin is not the same as penicillin resistance . Decreased susceptibility to penicillin has occurred worldwide from dissemination of several resistant pneumococcal clones, and, to a lesser extent, from excessive use of ciprofloxacin, macrolides, and trimethoprim-sulfamethoxazole (TMP-SMX) . Currently, penicillin resistance is defined by using a breakpoint of 2 microg/mL or more . Intermediately resistant strains (MIC 1-2 microg/mL) are also relatively sensitive depending on antibiotic concentration . Intermediate antibiotic susceptibility is concentration dependent . Antibiotic concentration at various body sites is determined by pharmacokinetic considerations . Except for very highly resistant strains, the treatment of penicillin-resistant S . pneumoniae causing bacteremia, sinusitis, otitis, bronchitis, or community-acquired pneumonia remains penicillin or any beta-lactam . Only in pneumococcal meningitis caused by penicillin-resistant pneumococci does the clinician have to use care in selecting an antipneumococcal antibiotic with adequate cerebrospinal fluid penetration and favorable kill ratios . Clinicians should be selective in antibiotic selection to minimize further decreases in penicillin susceptibility to S . pneumoniae . This is best achieved by using low-resistance potential antibiotics oral/intravenous mono-therapy at the full recommended dose . Therapeutic failure may occur in using lower doses at certain body sites . Macro-lides as monotherapy or as part of combination therapy should be minimized . Optimal therapy for non-central nervous system pneumococcal infection is with a respiratory quinolone (eg, levofloxacin, gatifloxacin, moxifloxacin), clindamycin, doxycycline, third-generation cephalosporins . For highly resistant pneumococci, levofloxacin, gatifloxacin, moxifloxacin, cefepime, meropenem, vancomycin, or linezolid may be used .

Appl Microbiol Biotechnol, 2002 Sep, 59(6), 713 - 7 Epub 2002 Aug 13.
Optimization of medium and cultivation conditions for capsular polysaccharide production by Streptococcus pneumoniae serotype 23F; Goncalves VM et al.; The influence of medium composition and culture conditions on Streptococcus pneumoniae serotype 23F cultivation was investigated in order to develop an industrial method for polysaccharide (PS) production . Acid-hydrolyzed casein (AHC) and dialyzed enzymatically hydrolyzed soybean meal (EHS) were investigated as nitrogen sources, and the vitamin solution of Hoeprich's medium and dialyzed yeast extract as vitamin sources . The influence of initial glucose concentration was also evaluated . In flask experiments, the best nitrogen source for PS production was AHC; EHS yielded small amounts of PS without interfering with bacterial growth . Dialyzed yeast extract provided an approximately 2-fold increase in PS production when compared to Hoeprich's vitamin solution . In a 5-l bioreactor, it was observed that the pneumococcus did not grow under aerobic conditions, CO(2) did not increase PS yield, glucose was inhibitory above 30 g l(-1), and the main glucose catabolism product was lactate, which had an inhibitory effect on cell growth . When anaerobic cultivation was performed under N(2) flow using the optimized medium, 240 mg l(-1) of soluble PS was obtained, which represents a 3-fold increase in yield as compared to that described in the published patent {Yavordios and Cousin (1983) European Patent 0 071515 A1} . Application of these results would considerably simplify upstream and downstream processes for PS production.

Eur J Clin Microbiol Infect Dis, 2002 Aug, 21(8), 611 - 2 Epub 2002 Aug 21.
Rare presentation of Streptococcus pneumoniae pneumonia with bacteremia and multiple subcutaneous abscesses; Shahin GS et al.; Reported here is the case of an apparently immunocompetent patient with Streptococcus pneumoniae pneumonia and bacteremia who presented with abscesses in multiple soft tissue sites . This unusual presentation provided a purulent aspirate for presumptive etiologic diagnosis by a Gram-stained smear.

Eur J Clin Microbiol Infect Dis, 2002 Aug, 21(8), 589 - 95 Epub 2002 Aug 15.
Clonal relationships among isolates of erythromycin-resistant Streptococcus pyogenes of different geographical origin; Kataja J et al.; The clonal relationships among 261 erythromycin-resistant Streptococcus pyogenes isolates collected in 1986-1997 from nine countries in Europe and North and South America were studied by using two molecular typing methods: Vir typing and random amplified polymorphic DNA (RAPD) analysis . A total of 49 different Vir genotypes (VTs) and 33 different RAPD patterns were noted among the 261 isolates . Isolates that shared the same VT and RAPD pattern were considered to belong to the same clone . Although as many as 60 different clones were found among the isolates studied, only seven clones, comprising 157 of the 261 (60%) isolates, were found in more than one country . Five of these seven clones expressed the M phenotype known to be associated with the drug efflux mechanism, and only two clones expressed the macrolide-lincosamide-streptogramin B-resistance phenotype . The results indicate a polyclonal spread of erythromycin-resistant Streptococcus pyogenes . Furthermore, predominance of the seven clones indicates that erythromycin-resistant Streptococcus pyogenes of the same clonal origin may be widely distributed and found in several different countries.

Am J Orthod Dentofacial Orthop, 2002 Sep, 122(3), 288 - 94
Evaluation of antimicrobial properties of orthodontic composite resins combined with benzalkonium chloride; Othman HF et al.; An antimicrobial agent, benzalkonium chloride (BAC), was added to a chemically cured composite resin, and the antimicrobial benefits and physical properties of the modified composite were evaluated . BAC was added to Reliance Phase II composite to create modified composites with BAC concentrations ranging from 0.25 to 2.50 wt% . Specimen disks of the modified composite were incubated with Streptococcus mutans for 48 hours, and an agar disk diffusion assay was used to measure zones of bacterial inhibition . Larger disks were suspended in brain-heart infusion medium containing 2 x 10(4) colony-forming units/mL Streptococcus sobrinus (10 mL, 2 wt% sucrose, 24 hours) to measure bacterial adherence to the adhesive; adherent cells were removed from the surface with 1 N NaOH, and the optical density of the cells was measured at 550 nanometers . Traction hooks were bonded to bovine teeth with the modified composite, and tensile bond strength was evaluated with a universal testing machine . Diametral tensile stress was also measured . The modified composite samples showed that antimicrobial activity increased with higher BAC content; no antimicrobial activity was measured for the original compound in either the disk diffusion or the bacterial adherence test . There were no significant differences (P <.05) in either tensile bond strength or diametral tensile stress among the modified composite groups and the original product . The incorporation of BAC in composite material added antimicrobial properties to the original compound without altering its mechanical properties.

Am J Vet Res, 2002 Sep, 63(9), 1298 - 301
Polymerase chain reaction-restriction fragment length polymorphism analysis of the SzP gene of Streptococcus zooepidemicus isolated from the respiratory tract of horses; Anzai T et al.; OBJECTIVE: To develop polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis for molecular typing of strains of Streptococcus zooepidemicus and to use the new typing method to analyze a collection of isolates from the respiratory tract of Thoroughbreds . SAMPLE POPULATION: 10 strains of S zooepidemicus, 65 isolates from the respiratory tract of 9 yearlings following long distance transportation, and 89 isolates from tracheal aspirates of 20 foals with pneumonia . PROCEDURE: Phenotypic variations in the SzP protein were detected by western immunoblot analysis . Using PCR-RFLP analysis, genotypes were obtained with primer sets from the SzP gene, followed by restriction endonuclease digestion of the amplicons . RESULTS: Unique genotypic patterns were obtained with a primer set designed from both ends of the structural gene and the restriction endonuclease DdeI . Forty-five isolates from the lymphoid tissue within the pharyngeal recess (ie, pharyngeal tonsil) of yearlings included 10 SzP genotypes and SzP phenotypes . Isolates from the trachea of each yearling were of a single genotype that was also present among isolates from the pharyngeal tonsil of the same horses . Isolates from tracheal aspirates of foals belonged to 14 genotypes . CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of the SzP gene by use of PCR-RFLP was effective for molecular typing of strains of S zooepidemicus in the study of respiratory tract disease in horses . Results of PCR-RFLP analysis indicate that a single strain of S zooepidemicus can migrate from the pharyngeal tonsil to the trachea at a high rate in horses undergoing long distance transportation.

Clin Rheumatol, 2002 Sep, 21(5), 378 - 81
Antistreptococcal response is exaggerated in children with familial Mediterranean fever; Yalcinkaya F et al.; Familial Mediterranean fever (FMF) is an autosomal recessive disorder . Although the pathogenesis of the disease is not yet completely understood, enhanced acute-phase responsiveness is considered to be one of the most important mechanisms . The presence of high levels of antistreptolysin O (ASO) antibodies and streptococcus-associated diseases, such as acute poststreptococcal glomerulonephritis (AGN) and acute rheumatic fever (ARF), has been reported in patients with FMF . In order to better understand the effect of FMF on antistreptococcal antibody response, we measured ASO and antideoxyribonuclease B (anti-DNAse B) levels in patients with FMF and compared them with those in healthy controls . The study consisted of two parts . In the first step, antistreptococcal antibody levels were analysed in 44 patients with FMF and 165 healthy children who had no history or clinical evidence of upper respiratory tract infection (URTI) for the last 4 months . In the second step, antistreptococcal antibody levels were measured in 15 patients with FMF and 22 healthy controls in response to documented group A beta-haemolytic streptococcal pharyngitis . In the first part of the study, ASO and anti-DNAse B levels in patients with FMF were found to be significantly higher than those in healthy controls (P<0.001) . In the second part, ASO and anti-DNAse B titres were found to be significantly higher in patients with FMF than in controls (P<0.001 and <0.05, respectively) 4 weeks after a positive throat culture . We concluded that patients with FMF have an exaggerated response to streptococcal antigens and might be prone to poststreptococcal non-suppurative complications, such as ARF.

Arch Neurol, 2002 Sep, 59(9), 1486 - 90
Vaccines to treat encephalitis lethargica: human experiments at the Neurological Institute of New York, 1929-1940; Louis ED; BACKGROUND: Encephalitis lethargica, first observed in 1915, became a pandemic . Because of its presumed infectious basis, there were early attempts to treat it with vaccines . The history of the use of these vaccines has not been analyzed . OBJECTIVE: To document the use of vaccines to treat patients with encephalitis lethargica, and, more specifically, the 1000 patients whose treatments took place with the support of the William J . Matheson Commission at the Neurological Institute of New York, NY (1929-1940) . MATERIALS AND METHODS: Archival materials were analyzed, including the files of the Matheson Commission and the medical records of patients evaluated at the Neurological Institute of New York . RESULTS: Two primary vaccines were used to combat encephalitis lethargica . The Rosenow vaccine was based on clinical and experimental evidence suggesting that the causative agent was Streptococcus viridans . The Levaditi C (later Gay F) vaccine was based on evidence that herpes simplex virus was the cause . During a therapeutic study conducted from 1929 through 1940, 1000 patients received treatment . Assessing therapeutic efficacy was problematic, but the Gay vaccine was considered more effective . CONCLUSIONS: Because of its presumed infectious basis, several vaccines were used to treat encephalitis lethargica, with the study at the Neurological Institute constituting the largest organized therapeutic attempt . Many of today's standard clinical trial methods were not practiced, which made it difficult to determine efficacy.

Arch Oral Biol, 2002 Aug, 47(8), 613 - 8
Enhanced neutrophil emigration and Porphyromonas gingivalis reduction following PGG-glucan treatment of mice; Niederman R et al.; Periodontal disease is the consequence of a mixed Gram-negative infection in the gingival sulcus and has been associated with deficits in the neutrophil response . A novel, and heretofore untested, alternative approach to therapy is the use of biological-response modulators that enhance the neutrophil response . Poly-beta1-6-glucotriosyl-beta1-3-glucopyranose glucan (PGG-glucan) is an immunomodulator, derived from yeast, which specifically enhances neutrophil priming, phagocytosis and bacterial killing while failing to induce inflammatory cytokine expression . The hypothesis tested was that PGG-glucan could enhance host resistance to a Gram-negative periodontal pathogen, Porphyromonas gingivalis . Chambers were implanted subcutaneously in the dorsolumbar region of C57BL/6J mice and allowed to heal for 14 days . PGG-glucan was administered subcutaneously to one-half of the animals and saline to the other half . In the first set of experiments the chambers were inoculated with P . gingivalis (A7436) at 4 x 10 (6), 4 x 10 (7), and 4 x 10 (8) colony-forming units (CFU) . In the second set of experiments the chambers were inoculated with 5 x 10 (8) CFU of either P . gingivalis or Streptococcus sanguis, a Gram-positive oral microbe that is not periodontopathic . Chambers were sampled over the following 2 weeks . The results demonstrated that: (1) . bacterial CFU and neutrophils increased with increasing bacterial inoculum (P<0.02); (2) . bacterial CFU were lower in the PGG-glucan-treated animals than in the saline controls (P<0.02); and (3) . neutrophil counts were higher in the PGG-glucan-treated animals than in the saline controls (P<0.01) . These results indicate that PGG-glucan significantly enhances neutrophil emigration and bacterial killing, thus decreasing the bacterial infection in this model system.

Obstet Gynecol, 2002 Sep, 100(3), 525 - 33
Perinatal antibiotic usage and changes in colonization and resistance rates of group B streptococcus and other pathogens; Spaetgens R et al.; OBJECTIVE: To quantify current antibiotic usage during the perinatal period and impact on vaginal-rectal colonizing organism resistance rates . METHODS: Swabs were obtained for culture of group B streptococcus and other bacteria from a cohort of 1207 pregnant women in Calgary, Alberta, at 36 weeks' gestation . Those women who received antibiotics during labor or after pregnancy and a 10% subset who received no antibiotics had repeat cultures at 6 weeks postpartum . Cultured organisms were tested for sensitivity to several antibiotics . RESULTS: Group B streptococcus was identified in 235 women (19.5%) in the antepartum period . Fifty-one percent of all participants received antibiotics (31.4% intrapartum) . Group B streptococcus prophylaxis was given to 215 (17.8%), whereas 83 (6.9%) group B streptococcus-negative women without fever during labor received antibiotics . Ampicillin (49%), cefazolin (28%), and penicillin (18%) were the most frequently used antibiotics . Resistance rates among group B streptococcus to erythromycin and clindamycin were 5.6% and 3.0%, respectively, whereas 20.6% of Escherichia coli were ampicillin resistant . Among antibiotic recipients, 6.3% of all bacteria that were initially sensitive on prenatal cultures to a specific antibiotic became resistant in the postnatal period, whereas 6.5% that were initially resistant became sensitive . CONCLUSION: Current prevention practices in our region were associated with perinatal antibiotic administration in over half of pregnant women . Ampicillin was the most common antibiotic administered . Some physicians are treating women who are group B streptococcus culture negative at term, a practice that is of no proven value . However, this was not associated with increased resistance for group B streptococcus or other organisms identified from maternal vaginal-rectal tracts.

East Afr Med J, 2001 Nov, 78(11), 581 - 5
Lower genital tract infections among pregnant women: a review; Marai W; OBJECTIVES: To determine the prevalence of lower genital tract infections, discuss briefly common maternal foetal complications associated with them and assess the usefulness of diagnostic algorithms in their management among pregnant women in the developing countries . DATA SOURCE: Articles published in English language since 1987 were looked through MEDLINE and OVID using key words supplemented by manual search in libraries except when full text of a subject was accessible via internet . STUDY SELECTION: Original and review articles addressing genital tract infections, associated complications and diagnostic evaluation in pregnant women were included . Emphasis was given to articles reported from developing countries . DATA EXTRACTION: A total of thirty five articles were retrieved and reviewed for information on the performance of diagnostic algorithms, prevalence rates and adverse maternal-foetal effects of lower genital tract infections in pregnancy . DATA SYNTHESIS: Lower genital tract infections are very common among apparently healthy looking pregnant women with an overall prevalence of 40-54% . Specific pathogens that were isolated from the vagina and/or cervix of asymptomatic pregnant women include: C . albicans (14-42%), T . vaginalis (11-20%), C . trachomatis (7-31%), N . gonorrhoea (0.5-14%) and group B streptococcus (4-25%) . Untreated, genital tract infections in pregnant women may result in: foetal loss, preterm labour, preterm birth, premature rupture of the membranes, low birthweight, eye and lung damage in the newborn . Although the feasibility is good, the performance of clinical algorithms in the evaluation and management of lower genital tract infections is worse in pregnant women and better results are achieved for vaginal infections than cervical infections . CONCLUSION: Routine screening for clinically important pathogens should be considered during antenatal service . There is a need to develop simple, cheap and reliable laboratory tests and better clinical algorithms for the diagnosis of reproductive tract infections among pregnant women.

Lancet Infect Dis, 2002 Sep, 2(9), 530 - 8
Fluoroquinolone resistance among Gram-positive cocci; Hooper DC; Resistance to fluoroquinolones among Gram-positive cocci has emerged as these antimicrobial agents have become extensively used in clinical medicine . Resistance is effected by changes in the bacterial target enzymes DNA gyrase and topoisomerase IV, which reduce drug binding, and by action of native bacterial membrane pumps that remove drug from the cell . In both cases, quinolone exposure selects for spontaneous mutants that are present in large bacterial populations, and which contain chromosomal mutations that alter the target protein or increase the level of pump expression . Resistance among clinical isolates has been greatest in Staphylococcus aureus and particularly among meticillin-resistant strains, in which both selection by quinolone exposure and transmission of clonal strains in health-care settings have contributed to high prevalence . Resistance in Streptococcus pneumoniae has also emerged in the community . Fluoroquinolone resistance has arisen in multidrug-resistant clones and its prevalence has been especially high in Hong Kong and Spain . Further spread and selection of such resistance could compromise the utility of a valuable class of antimicrobial agents, a point that emphasises the importance of the careful use of these agents in appropriate patients and doses, as well as careful infection-control practices.

Acta Otolaryngol, 2002 Jul, 122(5), 488 - 94
Suppression of epithelial ion transport transcripts during pneumococcal acute otitis media in the rat; Li HS et al.; Until recently, it was not feasible to conduct genome-wide screening for gene transcript variations that play key roles in the pathogenesis of otitis media . In this study microarray technology was used to profile differential gene expression patterns from rat middle ear mucosa at 12 and 48 h after Streptococcus pneumoniae challenge . Real-time polymerase chain reaction was performed for independent verification of the microarray results . Three ion transport mRNAs were simultaneously suppressed more than 4-fold at 12 h in bacteria-challenged ears, including Na,K-ATPase alpha I subunit (SPATPa1), sodium channel beta 2 subunit (SCNB2) and sodium-hydrogen exchange protein isoform 2 subunit (NHE2) . At 48 h after infection, the mRNA levels of SCNB2 and NHE2 had decreased 7- and 10-fold, respectively, whereas the relatively abundant SPATPa1 transcript showed recovery . The downregulation of Na(+)-transporting transcripts suggests a reduced number of epithelial cells and transporting proteins and/or the dysfunction of sodium transporters secondary to the bacterial infection . These changes can disrupt the coupling of the apical Na + entry and basolateral Na + extrusion, deplete the electrochemical Na+ transmembrane gradient, disrupt the intracellular osmotic equilibrium and lead to intracellular acidification and the accumulation of excess sodium, water and other organic and inorganic molecules in the middle ear cavity . Any or all of these changes may contribute to the initiation and persistence of middle ear mucosa inflammation and effusion during an episode of bacterial acute otitis media.

Acta Otolaryngol, 2002 Jul, 122(5), 479 - 87
Early structural tympanic membrane reactions to myringotomy: a study in an acute otitis media model; Spratley J et al.; Myringotomy (Myr) is one of the most frequently performed surgical procedures in children . However, events occurring in the early phases, i.e . a matter of hours, following Myr in the acute otitis media (AOM) model have not been described . The aim of the present study was to evaluate the early otomicroscopic and histopathologic reactions of the tympanic membrane (TM) after Myr during the course of AOM (AOM-Myr) . The left tympanic bulla from 36 healthy Sprague-Dawley rats was inoculated with Streptococcus pneumoniae type 3 . Forty-eight h later, at Day 0, 4 randomized animals were immediately sacrificed and the remaining animals were treated with bilateral Myr . Otomicroscopy and sacrifices were performed in series of 4 animals at 3, 6, 9, 12, 24 and 48 h, and 4 and 7 days . The AOM-Myr TMs were compared to non-infected Myr TMs (non-AOM-Myr) . The TMs were then dissected free and routinely processed for light and electron microscopy . AOM developed in all inoculated ears at Day 0 . In the pars tensa of the AOM-Myr TMs the reaction of the keratinocyte layer of the perforation border was already evident at 6 h . The lamina propria exhibited a strong inflammatory reaction, which became more organized from 12 h onwards . At Day 4 the perforations were closed in three-quarters of cases . At Day 7 all perforations were healed with a distorted scar . In the non-AOM Myr TMs a strong degranulation of mast cells and edema were found in the pars flaccida at 6 h . A keratin spur at the perforation border was not seen until 24 h . All perforations were patent on Day 7 and myringosclerotic deposits were abundant in these TMs . The infected TMs regenerated faster and closed their perforations at an earlier stage . These findings favor the hypothesis that there is a low risk of chronic perforations when myringotomizing AOM TMs.

J Pediatr Hematol Oncol, 2002 Aug-Sep, 24(6), 470 - 2
Streptococcus pneumoniae sepsis and meningitis during the penicillin prophylaxis era in children with sickle cell disease; Hord J et al.; The purpose of this study was to determine the age-related risks, disease-specific risks, and characteristics of serious pneumococcal infections in children with sickle cell disease (SCD) while penicillin prophylaxis was standard . The clinical experiences of three pediatric sickle cell programs spanning January 1, 1992, to May 31, 1998, were combined . Data were collected regarding the patients followed up and the characteristics of bacteremia and meningitis cases . Forty-seven pneumococcal infections (44 bacteremia, 3 meningitis) among 40 patients with SCD were observed . Forty infections occurred in children with homozygous hemoglobin S (SS) during 4108 patient-years at a median age of 22 months; 7 occurred in double heterozygous hemoglobin SC (SC) children during 1777 patient-years at a median age of 23 months . Ten infections occurred among 9 SS children 5 years or older . Most children in whom infections developed were reportedly taking prophylactic penicillin and when older than 24 months old had received Pneumovax (Merck & Co., Inc., West Point, PA, U.S.A . The following pneumococcal serotypes were identified in 15 cases studied: 6A, 6B, 9V, 14, 15B, 18B, 18F, 19F, and 23F . Infections resulted in five deaths and two strokes . The observed severe pneumococcal infection rate in SS children younger than 5 years was less than that reported before penicillin prophylaxis, supporting routine penicillin prophylaxis in this specific population . The optimal duration of penicillin prophylaxis in older children with SCD remains unknown . The administration of 7-valent Prevnar (Wyeth Lederle Vaccines, Philadelphia, PA, U.S.A.) to children younger than 24 months old with SCD should be beneficial, based on the serotype data.

Caries Res, 2002 Jul-Aug, 36(4), 288 - 93
Lack of effect of chlorhexidine varnish on Streptococcus mutans transmission and caries in mothers and children; Dasanayake AP et al.; In a randomized clinical trial, we evaluated the effect of a 10% chlorhexidine varnish (Chlorzoin) on the mother-child transmission of Streptococcus mutans and on subsequent caries experience . Chlorhexidine (n = 38) or a placebo varnish (n = 37) was applied to the dentitions of 75 mothers at a time when their first babies were about 6 months old (approximate time of first tooth emergence) . Three more applications at weekly intervals and subsequent applications at 6-month intervals followed the initial application . The mother-child pairs were followed up until the child's fourth birthday . Maternal salivary S . mutans levels in the treatment group remained significantly lower (p < 0.05) compared to the control group up to 12 months after the initial application . However, this intervention did not significantly alter the S . mutans colonization in children or the caries increment in either the mother or the child .

J Immunol, 2002 Sep 15, 169(6), 3217 - 22
A C-reactive protein mutant that does not bind to phosphocholine and pneumococcal C-polysaccharide; Agrawal A et al.; C-reactive protein (CRP), the major human acute-phase plasma protein, binds to phosphocholine (PCh) residues present in pneumococcal C-polysaccharide (PnC) of Streptococcus pneumoniae and to PCh exposed on damaged and apoptotic cells . CRP also binds, in a PCh-inhibitable manner, to ligands that do not contain PCh, such as fibronectin (Fn) . Crystallographic data on CRP-PCh complexes indicate that Phe(66) and Glu(81) contribute to the formation of the PCh binding site of CRP . We used site-directed mutagenesis to analyze the contribution of Phe(66) and Glu(81) to the binding of CRP to PCh, and to generate a CRP mutant that does not bind to PCh-containing ligands . Five CRP mutants, F66A, F66Y, E81A, E81K, and F66A/E81A, were constructed, expressed in COS cells, purified, and characterized for their binding to PnC, PCh-BSA, and Fn . Wild-type and F66Y CRP bound to PnC with similar avidities, while binding of E81A and E81K mutants to PnC was substantially reduced . The F66A and F66A/E81A mutants did not bind to PnC . Identical results were obtained with PCh-BSA . In contrast, all five CRP mutants bound to Fn as well as did wild-type CRP . We conclude that Phe(66) is the major determinant of CRP-PCh interaction and is critical for binding of CRP to PnC . The data also suggest that the binding sites for PCh and Fn on CRP are distinct . A CRP mutant incapable of binding to PCh provides a tool to assess PCh-inhibitable interactions of CRP with its other biologically significant ligands, and to further investigate the functions of CRP in host defense and inflammation.

J Infect, 2002 Jul, 45(1), 42 - 6
Group B streptococcal serotype distribution of isolates from colonized pregnant women at the time of delivery in United Arab Emirates; Amin A et al.; OBJECTIVE: To determine the maternal colonization rate with group B streptococcus (GBS) and to identify the most frequent GBS serotypes occurring in UAE women during labour . STUDY DESIGN: From February 1998 to January 1999, five hundred and sixty three pregnant women from a similar socio-economic and ethnic population were enrolled for the study . High vaginal swab cultures for GBS were obtained at the time of admission for delivery . Isolates were classified according to their capsular polysaccharide types (Ia, Ib, Ic, II-V) and c protein antigen compound . RESULTS: Fifty-seven (10.1%) of 563 mothers were found to be carriers of GBS . Among the isolates, serotype IV (26.3%) predominated followed by type Ia (21.0%), type III (17.6%), type V (12.3%) and nontypeable, which accounted for 15.8% . CONCLUSIONS: In view of the unknown status for GBS carrier rates in our community, this study suggests that about 10% of UAE women are colonized with group B streptococcus at delivery . The serotype distribution of the isolates in this population is different than those reported elsewhere with type IV predominating followed by type Ia and III .

Acupunct Med, 2002 Aug, 20(2-3), 105 - 6
Infected compartment syndrome after acupuncture; Shah N et al.; We present a case of septicaemia and compartment syndrome of the leg in a diabetic patient, following acupuncture to his calf . An emergency decompression fasciotomy was performed on the patient and gram-positive cocci were grown from the posterior compartment wound swab cultures and group A streptococcus from his blood cultures . He remained in the Intensive Therapy Unit postoperatively, requiring inotropic support and intravenous antibiotics for his septicaemia . We would like to remind acupuncturists, to consider the possibility of heightened risks in immunocompromised patients.

Hua Xi Kou Qiang Yi Xue Za Zhi, 1998 May, 16(2), 108 - 10, 140
{A study on anti-caries activity of genetic recombinant vaccine of Streptococcus lactis . II . Immunization in vein with recombinant S . lactis in pregnant rabbits}; Liu J et al.; The effects of immunization in vein with recombinant S . lactis HL107 carring the S . mutans surface protein PAc gene in pregnant rabbits were studied . The results indicated that specific anti-PAc IgG in serum and milk were obviously induced 1 week after immunization and retained at high level for several weeks . It suggests that the recombinant S . lactis HL107 possessing immunogenicity of S . mutans surface protein PAc is able to stimulate specific systemic immune response against PAc.

Am J Manag Care, 2002 Aug, 8(8), 713 - 27
Rational use of antibiotics to treat respiratory tract infections; File TM Jr et al.; OBJECTIVES: To foster the appropriate use of antimicrobial agents for respiratory tract infections and to review factors that should help achieve this objective . STUDY DESIGN: Review of evidence-based guidelines and recommendations for proper antibiotic drug use for respiratory tract infections . RESULTS AND CONCLUSIONS: Antibiotic drug overuse and inappropriate antibiotic drug selection are associated with increased drug resistance among respiratory pathogens (most notably, Streptococcus pneumoniae), possible progression to chronic disease, and increased treatment costs . Awareness of clinical manifestations that help differentiate viral from bacterial infection and the use of guidelines can promote the appropriate management of respiratory tract infections . Community-acquired pneumonia, acute bacterial rhinosinusitis, and selected cases of acute exacerbations of chronic bronchitis (50%) warrant antimicrobial therapy, whereas otitis media with effusion, acute bronchitis, and most rhinosinusitis are viral and do not require antibiotic therapy.

J Periodontol, 2002 Aug, 73(8), 843 - 51
Permeability of Streptococcus mutans and Actinobacillus actinomycetemcomitans Through guided tissue regeneration membranes and their effects on attachment of periodontal ligament cells; Hung SL et al.; BACKGROUND: Microbial colonization on barrier materials used in guided tissue regeneration (GTR) may adversely affect treatment outcomes . The purposes of this study were: 1) to compare the invasion of Streptococcus mutans and Actinobacillus actinomycetemcomitans through 3 GTR membranes, composed of expanded polytetrafluoroethylene (ePTFE; non-resorbable), a glycolide fiber composite, and type I collagen (both bioabsorbable), and 2) to explore the effects of bacteria on the attachment of periodontal ligament (PDL) fibroblasts onto these membranes . METHODS: Bacterial permeability was analyzed using a tube capped with a GTR membrane as a septum and filled with media . The tube was then placed in a bigger tube inoculated with S . mutans or A . actinomycetemcomitans . The passage of bacteria through the membranes into the inner tube was monitored . For cellular attachment experiments, primary human PDL cells were placed onto the GTR membranes with or without bacteria . Attached cells were analyzed by scanning electron microscopy (SEM) analysis . RESULTS: The ePTFE membrane had the best barrier effects followed by the collagen membrane and then the glycolide fiber composite membrane . Moreover, S . mutans passed through these membranes faster than A . actinomycetemcomitans . The attachment of PDL cells on the 3 membranes was also varied . The ePTFE membrane was the worst substrate for PDL fibroblast attachment . Moreover, both bacteria influenced the cellular attachment on the GTR membranes . CONCLUSIONS: Differences in the behavior of 3 GTR membranes penetrated by S . mutans and A . actinomycetemcomitans were demonstrated . The results suggest that attachment of PDL cells was affected on bacterial-contaminated GTR membranes, which may alter healing following membrane exposure.

MMWR Recomm Rep, 2002 Aug 16, 51(RR-11), 1 - 22
Prevention of perinatal group B streptococcal disease . Revised guidelines from CDC; Schrag S et al.; Group B streptococcus (GBS) remains a leading cause of serious neonatal infection despite great progress in perinatal GBS disease prevention in the 1990s . In 1996, CDC, in collaboration with other agencies, published guidelines for the prevention of perinatal group B streptococcal disease (CDC . Prevention of perinatal group B streptococcal disease: a public health perspective . MMWR 1996;45{RR-7}:1-24) . Data collected after the issuance of the 1996 guidelines prompted reevaluation of prevention strategies at a meeting of clinical and public health representatives in November 2001 . This report replaces CDC's 1996 guidelines . The recommendations are based on available evidence and expert opinion where sufficient evidence was lacking . Although many of the recommendations in the 2002 guidelines are the same as those in 1996, they include some key changes: * Recommendation of universal prenatal screening for vaginal and rectal GBS colonization of all pregnant women at 35-37 weeks' gestation, based on recent documentation in a large retrospective cohort study of a strong protective effect of this culture-based screening strategy relative to the risk-based strategy * Updated prophylaxis regimens for women with penicillin allergy * Detailed instruction on prenatal specimen collection and expanded methods of GBS culture processing, including instructions on antimicrobial susceptibility testing * Recommendation against routine intrapartum antibiotic prophylaxis for GBS-colonized women undergoing planned cesarean deliveries who have not begun labor or had rupture of membranes * A suggested algorithm for management of patients with threatened preterm delivery * An updated algorithm for management of newborns exposed to intrapartum antibiotic prophylaxis Although universal screening for GBS colonization is anticipated to result in further reductions in the burden of GBS disease, the need to monitor for potential adverse consequences of intrapartum antibiotic use, such as emergence of bacterial antimicrobial resistance or increased incidence or severity of non-GBS neonatal pathogens, continues, and intrapartum antibiotics are still viewed as an interim strategy until GBS vaccines achieve licensure.

Electrophoresis, 2002 Jul, 23(13), 2007 - 11
Softness of the bacterial cell wall of Streptococcus mitis as probed by microelectrophoresis; Rodriguez VV et al.; Chemical and structural complexity of bacterial cell surfaces complicate accurate quantification of cell surfaces properties . The presence of fibrils, fimbriae or other surface appendages on bacterial cell surfaces largely influence those properties and would therefore play a major function in interfacial phenomena as aggregation and adhesion . The electrophoretic softness and fixed charge density in the polyelectrolyte layer of nine Streptococcus mitis strains, usually carrying long sparsely distributed fibrils, were determined by the soft particle analysis using measured electrophoretic mobilities as a function of the ionic strength . In general, S . mitis cell surfaces are electrophoretically soft (1.0-2.5 nm) with a fixed negative charge density of -1.2 to -4.3 x 10(6) Cm(-3) . Further, a comparison with surfaces of other bacterial strains that are reported to be soft indicates that the Ohshima soft layer model does not provide information on the surface morphology causing the softness . The most likely reason is that the electroosmotic flow occurs only in the very outer region of thick extracellular surface layers . Nevertheless, determining the surface softness is essential for proper characterization of the cell surface electrostatics.

Biochem Biophys Res Commun, 2002 Sep 6, 296(5), 1329 - 33
A novel, anchorless streptococcal surface protein that binds to human immunoglobulins; Kawabata S et al.; We have characterized a novel surface protein from urea extract of whole cells of group A Streptococcus pyogenes (GAS) . A major protein band (35kD) was found to hybridize with human IgG by Western blotting . A search of the N-terminal amino acid sequence of this protein by using the GAS genome sequence database revealed an open reading frame that encoded a 38-kDa protein with a signal peptide sequence . We have named this protein streptococcal immunoglobulin-binding protein 35 (Sib35) . It was found to be an anchorless protein with no LPXTG motif, distinct from the M protein superfamily exhibiting immunoglobulin-binding activity, and partially secreted in the culture supernatant . Recombinant Sib35 was also shown to bind human IgA and IgM . The sib35 gene was found in all GAS strains examined, but not in oral, group B, C, or G streptococcal strains . These results suggest that Sib35 is a unique immunoglobulin-binding protein in GAS.

Mol Microbiol, 2002 Sep, 45(5), 1389 - 406
Large-scale identification of serotype 4 Streptococcus pneumoniae virulence factors; Hava DL et al.; Streptococcus pneumoniae (the pneumococcus) is carried in the nasopharynx of healthy individuals, but can spread to other host sites and lead to pneumonia, bacteraemia, otitis media and meningitis . Although it is logical to think a priori that differential gene expression would contribute to the ability of this pathogen to colonize different sites, in fact very few genes have been demonstrated to play tissue-specific roles in virulence or carriage . Using signature-tagged mutagenesis to screen 6149 mariner-transposon insertion strains, we identified 387 mutants attenuated for infection in a murine model of pneumonia . Among these mutants are ones with disruptions in a number of putative tissue-specific transcriptional regulators, surface proteins, metabolic proteins and proteins of unknown function, most of which had not previously been associated with virulence . A subset of these, including most of those with insertions in putative transcriptional regulators,was examined for phenotypes in murine models of bacteraemia and nasopharyngeal carriage . Four classes of mutants defective in infection models of the: (I) lung, (II) lung and blood, (III) lung and nasopharynx,and (IV) all three tissues were identified, thus demonstrating the existence of tissue-specific pneumococcal virulence factors . Included in these strains were two with disruptions in a genetic locus that putatively codes for a transcriptional regulator, three surface proteins and three sortase homologues . Mutation analysis revealed that three of the seven genes in this locus are virulence factors that are specific to mucosal surfaces.

J Antimicrob Chemother, 2002 Sep, 50(3), 403 - 6
Genotypic characterization of macrolide-resistant strains of Streptococcus pneumoniae isolated in Quebec, Canada, and in vitro activity of ABT-773 and telithromycin; Weiss K et al.; Increasing resistance of Streptococcus pneumoniae to macrolides represents a challenge for clinicians . New ketolides have an enhanced activity against macrolide-resistant strains . Four hundred and seventy-four strains of S . pneumoniae were collected during the 2000-2001 season in Quebec through a surveillance network . Macrolide resistance was 20.2%, and significantly higher in non-invasive strains versus invasive ones (22.4% versus 14.8%), and in children (30%) versus adults (14.8%) . For susceptible strains, MIC(90)s of ABT-773 and telithromycin were 0.008 and 0.015 mg/L . Among the 96 macrolide-resistant strains, 56 (58%) were erm(B), 35 (37%) carried the mef(A) gene, four were carrying both genes and one none . ABT-773 and telithromycin were very active against all these resistant strains irrespective of the resistance mechanism, with MIC(90)s of 0.25 and 0.5 mg/L, respectively.

J Antimicrob Chemother, 2002 Sep, 50(3), 349 - 60
Efficacy and pharmacodynamics of simulated human-like treatment with levofloxacin on experimental pneumonia induced with penicillin-resistant pneumococci with various susceptibilities to fluoroquinolones; Croisier D et al.; Newer fluoroquinolones, such as levofloxacin, have shown an enhanced in vitro and in vivo activity against penicillin-resistant Streptococcus pneumoniae infections . The frequency of S . pneumoniae with reduced susceptibility to quinolones, although currently low, raises the question of the therapeutic efficacy of levofloxacin on infection due to such strains . We used an animal model of penicillin-resistant pneumococcal pneumonia using six strains with various levels of susceptibility to ciprofloxacin and levofloxacin in rabbits to induce pneumonia, and simulated a human-like treatment of 500 mg twice a day for 48 h . Strains' susceptibility profiles for ciprofloxacin and levofloxaxin were (ciprofloxacin/levofloxacin MIC, mg/L; genotype): 0.5/0.5 (Cip0.5), 2/1 (Cip2), 4/1.75 (Cip4), 8/1.75 (parC mutation) (Cip8), 10/2 (parC mutation) (Cip10), 64/16 (parC and gyrA mutations) (Cip64), respectively . All the strains induced a crude pneumonia in all rabbits . Significant bacterial reductions at the end of treatment in lung and spleen were observed for the four former strains (P < 0.05) but not for the latter two . An AUC/MIC ratio of at least 32 identified 95% of an at least bacteriostatic effect (P = 0.038) and 76% of a bactericidal effect (P = 0.09) . Mutants were detected in treated animals infected with strains harbouring parC mutations (Cip8 and Cip10) and when the AUC/MIC ratio was between 13 and 31 . We conclude that levofloxacin is effective against experimental pneumonia due to pneumococci with MIC < 1.5 mg/L, ineffective on experimental pneumonia due to pneumococci with MIC > or = 2 mg/L, and could be associated with the appearance of mutants when a parC mutation is pre-existing.

Clin Infect Dis, 2002 Sep 15, 35(6), 721 - 7 Epub 2002 Aug 20.
The battle against emerging antibiotic resistance: should fluoroquinolones be used to treat children?
Mandell LA, Peterson LR, Wise R, Hooper D, Low DE, Schaad UB, Klugman KP, Courvalin P.
Inappropriate use of antibiotic drugs in humans and animals has led to widespread resistance among microbial pathogens . Resistance is the phenotypic expression corresponding to genetic changes caused by either mutation or acquisition of new genetic information . In some cases, multidrug resistance occurs . Streptococcus pneumoniae is one of the most important respiratory pathogens, playing a major role in both upper and lower respiratory tract infections . Pneumococcal resistance to antimicrobials may be acquired by means of horizontal transfer followed by homologous recombination of genetic material from the normal flora of the human oral cavity or by means of mutation . Resistance to penicillins and macrolides has been increasing for some time, but, recently, fluoroquinolone resistance has become an issue as well . We are concerned that, if fluoroquinolones are approved for use in children, their widespread use will result in rapid emergence of pneumococcal resistance, because children are more often colonized in the nasopharynx with high-density populations of pneumococci than are adults.

Clin Infect Dis, 2002 Sep 15, 35(6), 665 - 70 Epub 2002 Aug 26.
Population-based surveillance for postpartum invasive group a streptococcus infections, 1995-2000; Chuang I et al.; Estimates of disease burden and data on the sources of invasive postpartum group A streptococcus (GAS) infections will help guide public health action . Active, population-based surveillance was conducted in 9 regions from 1995 through 2000 . A case of GAS infection was defined as isolation of GAS from a sterile site in a resident of a surveillance area who was pregnant or in the postpartum period . Census and live birth data were used to calculate rates . Eighty-seven cases of postpartum GAS infection (2.2% of 3957 invasive GAS infections) occurred at 3%-8% of hospitals annually . We estimate that 220 cases occurred annually in the United States . Two or more cases were noted during 6 months at 8 hospitals, during 1 year at 13 hospitals, and during 2 years at 16 hospitals . Cases due to identical emm types clustered more frequently than expected by chance . Although postpartum GAS infections are rare, the clustering of infections due to identical strains suggests that some invasive cases may have a common source and, therefore, may be preventable.

J Clin Microbiol, 2002 Sep, 40(9), 3313 - 8
Molecular epidemiology of erythromycin resistance in Streptococcus pneumoniae isolates from blood and noninvasive sites; Amezaga MR et al.; Erythromycin-resistant isolates of Streptococcus pneumoniae from blood cultures and noninvasive sites were studied over a 3-year period . The prevalence of erythromycin resistance was 11.9% (19 of 160) in blood culture isolates but 4.2% (60 of 1,435) in noninvasive-site isolates . Sixty-two of the 79 resistant isolates were available for study . The M phenotype was responsible for 76% (47 of 62) of resistance, largely due to a serotype 14 clone, characterized by multilocus sequence typing as ST9, which accounted for 79% (37 of 47) of M phenotype resistance . The ST9 clone was 4.8 times more common in blood than in noninvasive sites . All M phenotype isolates were PCR positive for mef(A), but sequencing revealed that the ST9 clone possessed the mef(A) sequence commonly associated with Streptococcus pyogenes . All M phenotype isolates with this mef(A) sequence also had sequences consistent with the presence of the Tn1207.1 genetic element inserted in the celB gene . In contrast, isolates with the mef(E) sequence normally associated with S . pneumoniae contained sequences consistent with the presence of the mega insertion element . All MLS(B) isolates carried erm(B), and two isolates carried both erm(B) and mef(E) . Fourteen of the 15 MLS(B) isolates were tetracycline resistant and contained tet(M) . However, six M phenotype isolates of serotypes 19 (two isolates) and 23 (four isolates) were also tetracycline resistant and contained tet(M) . MICs for isolates with the mef(A) sequence were significantly higher than MICs for isolates with the mef(E) sequence (P < 0.001) . Thus, the ST9 clone of S . pneumoniae is a significant cause of invasive pneumococcal disease in northeast Scotland and is the single most important contributor to M phenotype erythromycin resistance.

J Clin Microbiol, 2002 Sep, 40(9), 3223 - 31
PCR-based identification of bacteria associated with endodontic infections; Fouad AF et al.; PCR primers that target the bacterial 16S rRNA genes (or the tuf gene for the genus Enterococcus) were used to identify 10 putative bacterial pathogens in root canals with necrotic pulp . In addition, the associations of these microorganisms with symptoms and a history of diabetes mellitus were investigated . Microbial samples from the root canals of 24 teeth with necrotic pulp were included in the study . PCR with universal bacterial primers identified bacterial DNA in 22 specimens; the remaining 2 specimens were from intact teeth that had been traumatized 6 months prior to treatment . PCR with specific primers showed that preoperative symptoms were significantly associated with the presence of Streptococcus spp . (P < 0.001 by chi-square analysis) . There was also a nonsignificant trend for symptoms to be associated with Fusobacterium nucleatum and Porphyromonas gingivalis (odds ratio, >2) and for diabetes mellitus to be associated with P . gingivalis and Porphyromonas endodontalis (odds ratio, >2) . Cloning and sequencing of the universal PCR product in one specimen revealed the presence of an organism related to the genus Olsenella, which has not previously been described in endodontic infections.

J Am Osteopath Assoc, 2002 Aug, 102(8), 431 - 6
Clinical experience with pneumococcal conjugate vaccines in infants and children; Jackson CR; Streptococcus pneumoniae is a leading cause of morbidity and mortality in pediatric patients, particularly in infants and children younger than 2 years . Each year, S pneumoniae is responsible for significant morbidity and mortality in the United States . During the past several decades, the emergence of penicillin-nonsusceptible and multidrug-resistant pneumococcal isolates has become a major cause for concern, with the overuse or inappropriate use of antibiotics playing a significant role in the increase of resistance . Because the resistance of S pneumoniae to antibiotics has complicated the treatment of pneumococcal infections, attention has focused on the need to prevent disease through vaccination . The objective of this article is to describe the rationale for the development of pneumococcal conjugate vaccines and to summarize the clinical experience to date with these vaccines in infants and children.

Yi Chuan Xue Bao, 2002, 29(8), 747 - 52
{Analysis of factors shaping S . pneumoniae codon usage}; Hou ZC et al.; Streptococcus pneumoniae is a Gram-positive bacteria causing community acquired pneumonia, bacteremia, meningitis and otitis media . As a human pathogen, S . pneumoniae is the most common bacterial cause of acute respiratory infection and otitis media and is estimated to result in over 3 million deaths in children every year worldwide . S . pneumoniae has played a pivotal role in the fields of genetics and microbiology . The complete genome of S . pneumoniae was sequenced and published recently . In order to have a further insight into the synonymous codon usage evolution and to study S . pneumoniae gene codon usage pattern in highly and lowly expressed genes, factors shaping synonymous codon usage pattern of S . pneumoniae were analyzed in this paper . Genes larger than of equal to 300bp of the complete genome of S . pneumoniae (1709 genes in total) were analyzed . The gene expression level (CAI, codon adaption index), RSCU (relative synonymous codon usage), Nc (effective codon numbers), A3s, T3s, G3s, C3s (the frequencies of the adenine, thymine, guanine and cytosine at the synonymous third position of codons, respectively), GC (frequency of guanine + cytosine in gene sequence), GC3s (frequency of guanine + cytosine at the synonymous third position of codons) values and multivariate statistics were calculated . The results show that there is a significant increment of cytosine (C) usage at the synonymous positions in highly expressed genes than lowly expressed genes, while lowly expressed genes tend to use guanine (G) at synonymous sites . Gene expression has a significant correlation with the first axis of correspondence analysis (COA; R = 0.86) and significant effects on codon usage by comparing the codon usage patterns of highly expressed genes and lowly expressed genes . The G + C content of genes has a moderately correlation with gene expression (R = 0.44) and the first axis of the COA (R = 0.51), and therefore shapes gene expression and codon usage in S . pneumoniae . The dataset is divided into 6 groups by gene length . Then, gene expression level, GC3s and Nc values are compared among 6 different gene length groups (> = 300 bp, 2000-2999 bp, 1500-1999 bp, 1000-1499 bp, 500-999 bp, < 500 bp) . CAI, GC3s and Nc values show some differences among different gene length groups . Protein hydrophobicities do not show significant influence on codon usage pattern . In summary, the natural selection on gene expression level and the base composition of genes are the major factors affecting codon usage of S . pneumoniae . Gene length shapes codon usage of S . pneumoniae in a minor way.

Appl Environ Microbiol, 2002 Sep, 68(9), 4253 - 8
Purification and immunogenicity of a recombinant Bordetella pertussis S1S3FHA fusion protein expressed by Streptococcus gordonii; Lee SF et al.; Acellular pertussis vaccines typically consist of antigens isolated from Bordetella pertussis, and pertussis toxin (PT) and filamentous hemagglutinin (FHA) are two prominent components . One of the disadvantages of a multiple-component vaccine is the cost associated with the production of the individual components . In this study, we constructed an in-frame fusion protein consisting of PT fragments (179 amino acids of PT subunit S1 and 180 amino acids of PT subunit S3) and a 456-amino-acid type I domain of FHA . The fusion protein was expressed by the commensal oral bacterium Streptococcus gordonii . The fusion protein was secreted into the culture medium as an expected 155-kDa protein, which was recognized by a polyclonal anti-PT antibody, a monoclonal anti-S1 antibody, and a monoclonal anti-FHA antibody . The fusion protein was purified from the culture supernatant by affinity and gel permeation chromatography . The immunogenicity of the purified fusion protein was assessed in BALB/c mice by performing parenteral and mucosal immunization experiments . When given parenterally, the fusion protein elicited a very strong antibody titer against the FHA type I domain, a moderate titer against native FHA, and a weak titer against PT . When given mucosally, it elicited a systemic response and a mucosal response to FHA and PT . In Western blots, the immune sera recognized the S1, S3, and S2 subunits of PT . These data collectively indicate that fragments of the pertussis vaccine components can be expressed in a single fusion protein by S . gordonii and that the fusion protein is immunogenic . This multivalent fusion protein approach may be used in designing a new generation of acellular pertussis vaccines.

Semin Pediatr Infect Dis, 2002 Jul, 13(3), 155 - 64
Pneumococcal vaccination of children; Overturf GD; Streptococcus pneumoniae is the most frequent cause of invasive bacterial infection in children younger than 2 years of age, reaching a peak incidence at 6 to 12 months of age . Pneumococci also cause many cases of pneumonia, sinusitis, and otitis media . Incidence rates of invasive infection in children with sickle cell disease, acquired or congenital splenectomy, or human immunodeficiency virus infection are 20- to 100-fold higher than are those of healthy children during the first 5 years of life . Other healthy children, such as those of American Indian, Native Alaskan, or African American descent, also have high rates of invasive infection, and those children enrolled in out-of-home care may have modestly increased risks . Pneumococcal polysaccharide polyvalent vaccines have been available for more than 2 decades but are limited in their usefulness for children because of their inability to induce protective antibody responses in children younger than 2 years of age and lack of immunologic memory . In contrast, pneumococcal protein conjugate vaccines induce presumptive protective responses in infants younger than 6 months, and immunologic memory further enhances responses after booster doses are given . Currently, a single heptavalent pneumococcal protein conjugate vaccine is licensed for use in the United States and is recommended for routine administration to all children, beginning at 2 months of age . It also is recommended for children between 24 and 59 months of age who are at high risk of acquiring invasive disease.

J Infect Dis, 2002 Sep 15, 186(6), 855 - 8 Epub 2002 Aug 16.
Seroepidemiologic studies of serotype VIII group B Streptococcus in Japan; Matsubara K et al.; Levels of antibody to serotype VIII group B Streptococcus (GBS) were surveyed in serum samples from 583 pregnant women, from 461 neonates born to these women, and from 4 mother-and-neonate pairs with early-onset serotype VIII sepsis . Colonization by serotype VIII GBS was associated with significantly higher serum concentrations of serotype-specific antibodies (geometric mean {GM}, 5.53 micro g/mL), compared with both noncolonization (1.53 micro g/mL) and colonization with other serotypes (2.19 micro g/mL) . There was excellent correlation between antibody levels in mothers and those in their neonates . The prevalence of positive antibody levels, when arbitrarily defined, according to antibody levels in neonatal sepsis (GM, 0.49 micro g/mL) as >1.0 micro g/mL, was 58% of all pregnant women and 85% of the women colonized by serotype VIII . This high serotype prevalence may explain, at least in part, why serotype VIII causes early-onset neonatal disease at rates lower than those which would be expected on the basis of its prevalence in mothers in Japan who are colonized by GBS.

J Infect Dis, 2002 Sep 15, 186(6), 798 - 806 Epub 2002 Aug 16.
Toll-like receptor 2-deficient mice are highly susceptible to Streptococcus pneumoniae meningitis because of reduced bacterial clearing and enhanced inflammation; Echchannaoui H et al.; Toll-like receptor-2 (TLR2) mediates host responses to gram-positive bacterial wall components . TLR2 function was investigated in a murine Streptococcus pneumoniae meningitis model in wild-type (wt) and TLR2-deficient (TLR2(-/-)) mice . TLR2(-/-) mice showed earlier time of death than wt mice (P<.02) . Plasma interleukin-6 levels and bacterial numbers in blood and peripheral organs were similar for both strains . With ceftriaxone therapy, none of the wt but 27% of the TLR2(-/-) mice died (P<.04) . Beyond 3 hours after infection, TLR2(-/-) mice had higher bacterial loads in brain than did wt mice, as assessed with luciferase-tagged S . pneumoniae by means of a Xenogen-CCD (charge-coupled device) camera . After 24 h, tumor necrosis factor activity was higher in cerebrospinal fluid of TLR2(-/-) than wt mice (P<.05) and was related to increased blood-brain barrier permeability (Evans blue staining, P<.02) . In conclusion, the lack of TLR2 was associated with earlier death from meningitis, which was not due to sepsis but to reduced brain bacterial clearing, followed by increased intrathecal inflammation.

Acta Crystallogr D Biol Crystallogr, 2002 Sep, 58(Pt 9), 1487 - 9 Epub 2002 Aug 23.
Crystallization and preliminary X-ray diffraction studies of the complete modular endolysin from Cp-1, a phage infecting Streptococcus pneumoniae; Monterroso B et al.; Endolysin from the phage Cp-1 (Cpl-1) cleaves the glycosidic beta1,4-bonds between the N-acetylmuramic acid and the N-acetylglucosamine of the pneumococcal cell wall . Cpl-1 has been crystallized using the hanging-drop vapour-diffusion method at 291 K . Diffraction-quality orthorhombic crystals of the native protein were obtained only after addition of the detergent n-decyl-beta-D-maltoside . Crystals belong to space group C222(1), with unit-cell parameters a = 77.949, b = 95.782, c = 129.282 A . Diffraction data to a resolution of 2.1 A were collected at a synchrotron facility.

J Biol Chem, 2002 Nov 1, 277(44), 41613 - 23 Epub 2002 Aug 23.
Recognition of bacterial capsular polysaccharides and lipopolysaccharides by the macrophage mannose receptor; Zamze S et al.; The in vitro binding of the macrophage mannose receptor to a range of different bacterial polysaccharides was investigated . The receptor was shown to bind to purified capsular polysaccharides from Streptococcus pneumoniae and to the lipopolysaccharides, but not capsular polysaccharides, from Klebsiella pneumoniae . Binding was Ca(2+)-dependent and inhibitable with d-mannose . A fusion protein of the mannose receptor containing carbohydrate recognition domains 4-7 and a full-length soluble form of the mannose receptor containing all domains external to the transmembrane region both displayed very similar binding specificities toward bacterial polysaccharides, suggesting that domains 4-7 are sufficient for recognition of these structures . Surprisingly, no direct correlation could be made between polysaccharide structure and binding to the mannose receptor, suggesting that polysaccharide conformation may play an important role in recognition . The full-length soluble form of the mannose receptor was able to bind simultaneously both polysaccharide via the carbohydrate recognition domains and sulfated oligosaccharide via the cysteine-rich domain . The possible involvement of the mannose receptor, either cell surface or soluble, in the innate and adaptive immune responses to bacterial polysaccharides is discussed.

Biochem Soc Trans, 2002 Aug, 30(4), 516 - 8
Amino acid sequence requirements in the human IgA1 hinge for cleavage by streptococcal IgA1 proteases; Senior BW et al.; All the IgA1 proteases of the different pathogenic species of Streptococcus cleave the hinge of the alpha chain of human IgA1 only at one proline-threonine peptide bond . In order to study the importance of these amino acids for cleavage, several hinge mutant recombinant IgA1 antibodies were constructed . The mutations were found to be without major effect upon the structure or functional abilities of the antibodies . However, they had a major effect upon their sensitivity to cleavage by some of the IgA1 proteases.

Respir Med, 2002 Aug, 96(8), 580 - 5
The effects of pneumolysin and hydrogen peroxide, alone and in combination, on human ciliated epithelium in vitro; Feldman C et al.; We have investigated the effects of pneumolysin and H2O2, putative virulence factors of Streptococcus pneumoniae, on the ciliary beat frequency and structural integrity of human ciliated epithelium in vitro . Human ciliated epithelium was obtained by brushing the inferior nasal turbinate of healthy human volunteers . Ciliary slowing (CS) was measured using a photo-transistor technique and epithelial damage (ED) was documented using a visual scoring index . Effects of recombinant pneumolysin (100 ng/ml), a mutant pneumolysin preparation with markedly reduced haemolytic activity (100 ng/ml) and reagent H2O2 (100 microM) were measured alone and in combination, in the absence and presence of catalase (1000 units/ml) . When used individually, both recombinant pneumolysin and H2O2 caused significant (P < 0.05) CS and ED . The effects of H2O2 but not those of pneumolysin were almost completely attenuated by catalase, while the mutant pneumolysin preparation did not cause significant CS or ED . When used in combination, the effects of pneumolysin and H2O2 on CS and ED were additive as opposed to synergistic . These actions of pneumolysin and H2O2 may contribute to the pathogenesis of respiratory tract infections caused by the pneumococcus.

J Infect Dis, 2002 Aug 15, 186(4), 562 - 5 Epub 2002 Jul 24.
Pneumolysin activates the synthesis and release of interleukin-8 by human neutrophils in vitro; Cockeran R et al.; The effects that the Streptococcus pneumoniae-derived, proinflammatory toxin, pneumolysin (8.37 and 41.75 ng/mL), has on the production of interleukin (IL)-8 and tumor-necrosis factor (TNF)-alpha by human neutrophils have been investigated in vitro . Total and extracellular IL-8 and TNF-alpha were assayed by enzyme-linked immunosorbent assay, and flow cytometry and colorimetric procedures were used to detect intracellular cytokine and cytokine messenger RNA, respectively . Treatment of neutrophils with pneumolysin either alone or in combination with the chemotactic tripeptide, N-formyl-l-methionyl-l-leucyl-l-phenylalanine (1 microM), resulted in a time-dependent (maximal at 6 h) increase in synthesis and release of IL-8 but not of TNF-alpha, which was associated with increased expression of IL-8 messenger RNA transcripts and was abrogated by either cycloheximide (10 microg/mL) or depletion of Ca(2+) from the cell-suspending medium . These interactions between the toxin and neutrophils may contribute to the exaggerated pulmonary inflammatory responses caused by pneumolysin-producing strains of the pneumococcus.

Rev Med Chil, 2002 Jun, 130(6), 677 - 80
{Hemolytic-uremic syndrome and Streptococcus pneumoniae}; Reynolds E et al.; Hemolytic-uremic syndrome (HUS) is an uncommon complication of pneumococcal infection . Highly suggesting findings in a patient with Streptococcus pneumoniae infection are: microangyopatic hemolytic anemia, thrombocytopenia and acute renal failure . We report a 41 years old woman, admitted to the hospital due to a severe pneumonia, that required the surgical drainage of an empyema . On admission, a drop in packed red cell volume from 41 to 25%, the presence of schistocytes in the blood smear, an elevation of LDH to 1,700 IU/L, a fall in haptoglobin to 5.8 mg/dL and a thrombocytopenia of 72,000 per mm3 were detected . These alterations coincided with an oliguric acute renal failure . She was treated with hemodialysis and the hemolytic syndrome was managed with plasmapheresis . She was discharged 35 days after admission and in the follow up, after 2.5 months, her serum creatinine is 1.2 mg/dL and her packed red cell volume is 41%.

Indian J Ophthalmol, 2002 Jun, 50(2), 109 - 14
In-vitro efficacy of antibacterials against bacterial isolates from corneal ulcers; Bharathi MJ et al.; PURPOSE: To analyse the in-vitro efficacy of commonly used antibacterials against bacterial pathogens from corneal ulcers . METHODS: We evaluated 596 patients seen over 18 months, period, September 1999 through March 2001 . Corneal scrapings were subjected to microscopy and cultures using standard protocols . Antibacterial susceptibility of isolated bacteria were determined by the Kirby-Bauer disc-diffusion method . RESULTS: 626 bacterial pathogens were isolated from 596 corneal ulcer cases . 411(65.65%) were gram positive cocci Streptococcus pneumoniae (41.85%) was the predominant bacterial species . The antibacterial susceptibility was: 451(72.04%) to cefazolin, 471(75.24%) to chloramphenicol; 321(51.28%) to cephaloridine; 430(68.69%) to vancomycin; 564(90.09%) to ciprofloxacin; 429(68.53%) to norfloxacin; 464(74.12%) to gentamicin and 202(32.27%) to co.trimoxazole . CONCLUSION: This study provides information on the efficacy of ocular antibacterials commonly used against bacterial pathogens of keratitis . It is hoped that this information will help decision-making in empiric initial treatment of bacterial keratitis.

Am J Obstet Gynecol, 2002 Aug, 187(2), 495 - 500
Antepartum use of antibiotics and early-onset neonatal sepsis: the next 4 years; Towers CV et al.; OBJECTIVE: The purpose of this study was to analyze the incidence of early-onset neonatal sepsis and the presence of antibiotic resistance of the isolated bacteria and its relationship to antibiotic chemoprophylaxis that occurred during the 4 years that followed the publication of the most recent group B streptococcal guidelines . STUDY DESIGN: A prospective cohort study was performed between January 1, 1997, and December 31, 2000 . All cases of early-onset neonatal sepsis were gathered prospectively . Data concerning the use of antepartum antibiotics, the isolated bacteria, and the presence of drug resistance were collected . These data were analyzed separately and were combined with published data from the preceding 6 years . RESULTS: A total of 26 cases of blood culture-proved early-onset neonatal sepsis occurred during the current 4-year study period . Group B Streptococcus was responsible for 10 cases, and the remaining 16 cases were non-group B streptococcal organisms . Of these 16 cases, 11 parturients received antibiotic chemoprophylaxis, and 10 of the isolates (91%) were resistant to the drug that was administered, compared with only one resistant bacteria (20%) in the 5 parturients who did not receive treatment (P =.01) . In combining these 16 cases with the cases from the preceding 6 years, a total of 43 cases of non-group B streptococcal sepsis occurred in 49,788 deliveries . Of these, 26 mothers were given antepartum antibiotics, and 23 of the bacterial isolates (88%) exhibited resistance, compared with only 3 of the 17 cases (18%) in which antibiotics were not dispensed (P <.00001) . However, because the overall use of antepartum antibiotics increased over time, the attack rate for early-onset group B Streptococcus significantly decreased by 75% (P <.000001) . CONCLUSION: When early-onset neonatal sepsis develops in a case in which antepartum chemoprophylaxis was used, the bacterial isolate will most likely demonstrate resistance to the antibiotic that was administered . However, the development of early-onset group B streptococcal neonatal sepsis significantly decreased as the use of antepartum antibiotics increased . Thus, the number of prevented infections from antepartum antibiotic use may still outweigh the problems that are seen when resistant bacterial infections arise . Nevertheless, based on the current protocols, a large number of parturients are candidates for antibiotic chemoprophylaxis and this, in conjunction with the global concern of bacterial drug resistance, should be motivation to examine alternative methods, such as vaginal washing or immunotherapy, for decreasing infection.

J Immunol, 2002 Sep 1, 169(5), 2561 - 9
The bacterial superantigen streptococcal mitogenic exotoxin Z is the major immunoactive agent of Streptococcus pyogenes; Unnikrishnan M et al.; The gene encoding streptococcal mitogenic exotoxin Z (SMEZ) was disrupted in Streptococcus pyogenes . Despite the presence of other superantigen genes, mitogenic responses in human and murine HLA-DQ transgenic cells were abrogated when cells were stimulated with supernatant from the smez(-) mutant compared with the parent strain . Remarkably, disruption of smez led to a complete inability to elicit cytokine production (TNF-alpha, lymphotoxin-alpha, IFN-gamma, IL-1 and -8) from human cells, when cocultured with streptococcal supernatants . The potent effects of SMEZ were apparent even though transcription and expression of SMEZ were barely detectable . Human Vbeta8(+) T cell proliferation in response to S . pyogenes was SMEZ-dependent . Cells from HLA-DQ8 transgenic mice were 3 logs more sensitive to SMEZ-13 than cells from HLA-DR1 transgenic or wild-type mice . In the mouse, SMEZ targeted the human Vbeta8(+) TCR homologue, murine Vbeta11, at the expense of other TCR T cell subsets . Expression of SMEZ did not affect bacterial clearance or survival from peritoneal streptococcal infection in HLA-DQ8 mice, though effects of SMEZ on pharyngeal infection are unknown . Infection did lead to a rise in Vbeta11(+) T cells in the spleen which was partly reversed by disruption of the smez gene . Most strikingly, a clear rise in murine Vbeta4(+) cells was seen in mice infected with the smez(-) mutant S . pyogenes strain, indicating a potential role for SMEZ as a repressor of cognate anti-streptococcal responses.

J Bacteriol, 2002 Sep, 184(18), 4988 - 5000
Purification and polar localization of pneumococcal LytB, a putative endo-beta-N-acetylglucosaminidase: the chain-dispersing murein hydrolase; De Las Rivas B et al.; The DNA region encoding the mature form of a pneumococcal murein hydrolase (LytB) was cloned and expressed in Escherichia coli . LytB was purified by affinity chromatography, and its activity was suggested to be the first identified endo-beta-N-acetylglucosaminidase of Streptococcus pneumoniae . LytB can remove a maximum of only 25% of the radioactivity from {(3)H}choline-labeled pneumococcal cell walls in in vitro assays . Inactivation of the lytB gene of wild-type strain R6 (R6B mutant) led to the formation of long chains but did not affect either total cell wall hydrolytic activity at the stationary phase of growth or development of genetic competence . Longer chains were formed when the lytB mutation was introduced into the M31 strain (M31B mutant), which harbors a complete deletion of lytA, which codes for the major autolysin . Furthermore, the use of this mutant revealed that LytB is the first nonautolytic murein hydrolase of pneumococcus . Purified LytB added to pneumococcal cultures of R6B or M31B was capable of dispersing, in a dose-dependent manner, the long chains characteristic of these mutants into diplococci or short chains, the typical morphology of R6 and M31 strains, respectively . In vitro acetylation of purified pneumococcal cell walls did not affect the activity of LytB, whereas that of the LytA amidase was drastically reduced . On the other hand, the use of a translational fusion between the gene (gfp) coding for the green fluorescent protein (GFP) and lytB supports the notion that LytB accumulates in the cell poles of either the wild-type R6, lytB mutants, or ethanolamine-containing cells (EA cells) . The GFP-LytB fusion protein was also able to unchain the lytB mutants but not the EA cells . In contrast, translational fusion protein GFP-LytA preferentially bound to the equatorial regions of choline-containing cells but did not affect their average chain length . These observations suggest the existence of specific receptors for LytB that are positioned at the polar region on the pneumococcal surface, allowing localized peptidoglycan hydrolysis and separation of the daughter cells.

Arch Dis Child, 2002 Sep, 87(3), 202 - 6
Causes of morbilliform rash in a highly immunised English population; Ramsay M et al.; AIMS: To determine the causes of morbilliform rash and fever in a population with high vaccination coverage for measles and rubella . METHODS: Comprehensive laboratory investigation additional to routine oral fluid testing of children presenting to primary care physicians in East Anglia, England . RESULTS: Laboratory confirmation of infection was obtained in 93 (48%) of 195 children: parvovirus B19 in 34 (17%); group A streptococcus in 30 (15%); human herpesvirus type 6 in 11 (6%); enterovirus in nine (5%); adenovirus in seven (4%); and group C streptococcus in six (3%) (four individuals tested positive for two agents) . None had measles or rubella . CONCLUSIONS: Oral fluid testing to cover infections additional to measles and rubella aids clinical management and is likely to maintain uptake of testing, which is essential for measles and rubella surveillance in highly immunised low incidence populations.

Hybrid Hybridomics, 2002 Aug, 21(4), 225 - 32
Analyses of Streptococcus mutans in saliva with species-specific monoclonal antibodies; Gu F et al.; Three species-specific monoclonal antibodies (MAbs) against Streptococcus mutans were used to detect and quantify S . mutans levels in saliva . This study shows that MAb-based salivary S . mutans tests exhibit significantly higher specificity and sensitivity than the commonly used selective culture method . Examination of nearly 2,000 human saliva samples shows that S . mutans counts in human saliva vary from less than 10,000 to a high 36 million cells/mL . Over 15% of the saliva samples examined have salivary S . mutans counts over 500,000 cells/mL . When saliva samples were collected at different time points during a day, the number of salivary S . mutans in the same human subject varied, especially before and after sugar uptake . Additionally, data obtained from stimulated versus unstimulated saliva in the same human subjects differed greatly and appear to be completely uncorrelated . This study provides useful information and tools for analyzing the role of S . mutans in human dental caries.

Ann Fr Anesth Reanim, 2002 Jul, 21(7), 603 - 5
{Fulminant mediastinitis from Streptococcus pneumoniae following cardiac surgery}; Souza Neto EP et al.; A 62-year-old patient was scheduled for coronary artery bypass surgery because of tritroncular coronary artery disease . The early postoperative period was uncomplicated until the 10th postoperative day when purulent fluid appeared from the sternal wound . Cultures of blood, wound and mediastinal tissues yielded Streptococcus pneumoniae with decreased susceptibility to penicillin G . Despite prompt surgical debridement and appropriate antibiotics, a septic shock with multiorgan failure occurred and the patient died on the 19th postoperative day . Although Streptococcus pneumoniae is uncommonly implicated in postoperative mediatinitis, it frequently leads to multiple organ failure and death.

J Formos Med Assoc, 2002 Jun, 101(6), 429 - 31
Rhabdomyolysis associated with Streptococcus pneumoniae bacteremia in a splenectomized patient; Shih KY et al.; Invasive infection due to Streptococcus pneumoniae associated with rhabdomyolysis is rare . We report the case of a 31-year-old splenectomized man with pneumococcal bacteremia and paranasal sinusitis who presented with flu-like symptoms preceding a fulminant course of sepsis and rhabdomyolysis with acute renal failure and elevated creatinine phosphokinase . Although the possible mechanisms of rhabodomyolysis associated with pneumococcal infection remain unclear, this report may serve to alert clinicians of the need to prevent fulminant pneumococcal infection by vaccination and treatment with antibiotic prophylaxis in splenectomized patients.

J Med Assoc Thai, 2002 Jun, 85 Suppl 1, S378 - 82
Outbreak of uncommon type of group A streptococcal pharyngitis among cadets at the Chulachomklao Royal Military Academy, Nakhon Nayok, Thailand; Orataiwun P et al.; A large outbreak of group A Streptococcus (GAS) pharyngitis occurred among 285 cadets at the Chulachomklao Royal Military Academy, Nakhon Nayok between September 22 and 27, 1996 . An epidemiologic investigation was conducted to determine the source of infection . It seemed that respiratory droplets were the mechanism of spread, although foodborne transmission could not be excluded . To assess the presence of the outbreak strain in the community, conventional serotyping and molecular typing by emm sequencing were performed . The results demonstrated the advantage of molecular typing compared to serotyping and suggested that the outbreak was caused by the same strain . Interestingly, the involvement of the causative emm79 strain, which is an uncommon type of GAS disease, in a large number of patients may imply the invasive potential of this organism.

J Med Assoc Thai, 2002 Jun, 85 Suppl 1, S217 - 30
Infectious keratitis at King Chulalongkorn Memorial Hospital: a 12-year retrospective study of 391 cases; Boonpasart S et al.; A retrospective study of 391 severe infectious keratitis admitted to King Chulalongkorn Memorial Hospital from January 1988 to December 2000 were analyzed . Most patients came from the central part of Thailand . There were 2 bimodal peak incidence distributions which fell in the age group 21-30 and 51-60 years of age . The most common predisposing to corneal ulceration was trauma from several materials, including leaves, branches, dust and stone, which accounted for 47.82 per cent . Culture results were collected 74.68 per cent (292/391) . The data showed negative culture results of 52.74 per cent (154/292), positive results occurred in 47.26 per cent (138/292); including bacteria 32.53 per cent (95/292), fungus 11.64 per cent (34/292), virus 2.05 per cent (6/292) and mixed organism 1.02 per cent (3/292) . Pseudomonas aeruginosa was the most common bacteria isolated; 47 per cent . The second most common was Streptococcus pneumoniae which accounted for 9 per cent . Fusarium spp was the most common fungus found (34.29%); Aspergillus and Curvularia spp were the next (20.0% each) . Herpes simplex was the most common virus isolated; 83.3 per cent . The treatment of infectious keratitis included application of topical/intraocular injection of antimicrobial agent and surgery, which accounted for 184 cases . Penetrating keratoplasty was the most common surgery performed, 34.24 per cent (63/184), followed by evisceration and enucleation accounted for 25 per cent (46/184).

J Med Assoc Thai, 2002 Jun, 85 Suppl 1, S109 - 17
Streptococcus suis infection in Thailand; Vilaichone RK et al.; This is a retrospective study of Streptococcus suis infection in humans submitted to the National Streptococcal Referrence Center of Thailand from 1994 to 2001 . There were 11 men and 6 women whose mean age was 46.24 years (range 1 month to 75 years) . Among the men, two had known occupational and behavioral exposure to pork or meat products . Among the women, one was a butcher and three were housewives . Half of the patients had underlying diseases . One patient had congenital hydrocephalus, three patients had rheumatic heart disease and three were alcoholics . Two of these patients had a history of skin injury before infection . Nine patients had evidence of acute bacterial meningitis, four patients had infective endocarditis, two had the sepsis syndrome and two suffered from pneumonia and spontaneous bacterial peritonitis . The authors suspected that many cases are not reported particularly where pig-rearing or pork consumption are common . In the absence of an effective vaccine, prevention by public health surveillance is important . Prompt treatment of any cuts and wounds among pork-handlers is a sensible precaution . Furthermore, a high index of suspicion and early detection in order to identify and apply effective antimicrobial agents is necessary to successfully treat S . suis infection.

Mil Med, 2002 Aug, 167(8), 671 - 7
A conjugate vaccine for the prevention of pediatric pneumococcal disease; Murray D et al.; The use of the pneumococcal 7-valent conjugate vaccine (PCV7 {Prevnar}, Wyeth Lederle Vaccines), and the impact it is likely to have on pneumococcal disease are reviewed . Pneumococcal disease in infants and young children is a major health care burden, and the increase in antibiotic resistance among pneumococci has complicated disease management . The 23-valent polysaccharide pneumococcal vaccines do not protect infants and children younger than 2 years of age . PCV7 is effective in this population and should dramatically reduce the incidence of invasive pneumococcal disease and have an impact on the incidence of infections caused by Streptococcus pneumoniae serotypes present in the vaccine . Research has shown that pneumococcal conjugate vaccines reduce nasopharyngeal carriage of vaccine serotype S . pneumoniae, including antibiotic-resistant strains . Routine immunization is expected to substantially reduce the morbidity and mortality associated with invasive pneumococcal disease in children, and coupled with expected herd immunity and decreased antibiotic selective pressure, it should have a positive impact beyond the immunized population.

J Biochem Mol Biol Biophys, 2002 Feb, 6(1), 23 - 8
Existence of two emm-like "mrp" and "emm" genes in the mga regulon of the Streptococcus pyogenes strain ST4547; Eshaghi M et al.; Streptococcus pyogenes ST4547 is an opacity factor negative strain, which has been recently reported as a new emm type from Malaysia . Nucleotide sequencing of the mga regulon of this strain showed the existence of two emm-like genes . The emm gene located upstream of the scpA gene comprises 1305 nucleotides encoding the putative precursor M protein of 435 amino acids in length with an M(r) of 49 kDa . or a predicted mature protein of 394 amino acids with an M(r) of 44.8 kDa . Another gene mrpST4547 was located upstream of the emm gene and downstream of the mga gene . The sequence of this mrp gene comprises 1167 nucleotides encoding a predicted protein of 388 amino acids in length with an M(r) of 42.2 kDa . or a predicted mature protein of 347 amino acids with an M(r) of 37.9 kDa . The mga regulon of strain ST4547 has a mosaic structure comprising segments, which originated from different OF positive and OF negative strains . The sequences flanking the hyper-variable and C repeats of the emmST4547 gene showed high similarity to corresponding regions in the mga regulon of OF positive strains notably M15, M4, M22 and M50 . In contrast, the sequence within the hyper-variable and C repeat regions of the emmST4547 gene revealed high similarity to equivalent regions in the OF negative strains . These data indicates that horizontal transfer of emm-like gene could have occurred between OF positive and OF negative strains resulting in architectural divergence in the mga regulon.

Expert Opin Pharmacother, 2002 Sep, 3(9), 1341 - 64
Quinupristin/dalfopristin; Blondeau JM et al.; Gram-positive pathogens are associated with both community- and hospital-acquired infections . These infections may be life-threatening in hospitalised patients, especially in those with significant underlying acute or chronic diseases . Prompt and appropriate antimicrobial therapy is essential for avoiding morbidity and mortality . The concept of appropriate therapy is being redefined by increasing antimicrobial resistance, especially amongst Gram-positive pathogens . This has been most dramatic with penicillin-resistant Streptococcus pneumoniae in the community, including cross-resistance to other classes of antimicrobial agents . In the US, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) with community isolates is significant . For hospital-acquired Gram-positive pathogens, MRSA, vancomycin-resistant Enterococcus species and vancomycin-intermediate resistant and -resistant S . aureus are a great concern, particularly as the frequency of recovery of these pathogens from infected patients increases . The net result of these various resistance issues is a reduction in the number of appropriate antimicrobial agents for treating infected patients . Quinupristin/dalfopristin is a parental streptogramin with a spectrum of activity that includes Gram-positive pathogens, including those resistant to other classes of antimicrobial compounds . In this review, data summarising the frequency of recovered Gram-positive pathogens from various infectious diseases, the escalating prevalence of resistance amongst Gram-positive pathogens and the factors making quinupristin/dalfopristin a suitable agent for treating patients infected with Gram-positive organisms will be discussed.

Arq Bras Cardiol, 2002 Jun, 78(6), 592 - 7
Multiple embolism in a female patient with infective endocarditis . Low back pain and hematuria as the initial clinical manifestations; Vieira ML et al.; A 59-year-old female patient with mitral valve prolapse and a previous history of lumbosacral spondyloarthrosis and lumbar disk hernia had an episode of infective endocarditis due to Streptococcus viridans, which evolved with peripheral embolism to the left kidney, spleen, and left iliac artery, and intraventricular cerebral hemorrhage . Her clinical manifestations were low back pain and hematuria, which were initially attributed to an osteoarticular condition . Infective endocarditis is a severe polymorphic disease with multiple clinical manifestations and it should always be included in the differential diagnosis by clinicians.

Med Dosw Mikrobiol, 2002, 54(1), 75 - 86
{Microbiologic analysis of results from blood cultures}; Budak A et al.; The aim of our investigations was the microbiological analysis together with the evaluation of sensitivity of bacteria frequently isolated from blood cultures . Blood samples were taken from patients with symptoms suggesting bacteremia in Rydygier's Hospital in Cracow . A total of 11,170 blood samples taken from 1997 to 2000 were tested . Automatic VITAL system (bioMerieux) was applied to culture and detect microorganisms . Bacteria were identified by ATB system (bioMerieux) . Susceptibility was detected by ATB and disc diffusion method . Percentage of positive results relating to detection of microorganisms of clinical significance was 16.9% (1891 cultures) . Staphylococcus spp . (Staph . epidermidis in range 22.8% to 21.9%), Enterococcus spp . and Streptococcus spp . were most frequently isolated species among aerobic Gram-positive bacteria . In 2000, compared to 1997 the number of isolates of MRSA increased considerably (from 1.8% to 6.8%) . In blood infections the increase of frequency of E . coli bacteria was also noted: 6.1% and 11.4% in 1997 and 2000, respectively . Among non-fermentant bacilli the percentage of occurrence of P . aeruginosa in the period of 4 years was comparable in the range 7.3% in 1997 to 7.2% in 2000 . The increase in the frequency of blood infections of A . baumanii was also noticed (respectively from 4.8% to 9.9%) . Susceptibility of P . aeruginosa strains to selected beta-lactame antibiotics and aminoglycosydes increased in 2000 in comparison to 1999 . A . baumanii strains were 100% sensitive only to imipenem.

Pediatr Nephrol, 2002 Aug, 17(8), 638 - 42 Epub 2002 May 25.
Immunization in children with chronic renal failure; Laube GF et al.; Infections jeopardize children on immunosuppression after organ transplantation . Immunization is protective in healthy children . The aims of this study were to analyze the rate and efficacy of immunization in 62 children undergoing dialysis and renal transplantation (RTPL) between 1987 and 2000 . The analysis was based on clinical findings, vaccination certificates, and measurement of specific serum antibodies . A member of the renal unit administered vaccinations . All 62 patients were immunized against diphtheria, tetanus, pertussis, poliomyelitis, measles, mumps, rubella, and hepatitis B . Since introduction in 1991 and 1995, 44 and 42 children were also vaccinated against influenza and Hemophilus influenzae type b, respectively . Of 16 patients with a negative history, 14 were given varicella vaccine; 16 children on peritoneal dialysis (PD) or with nephrotic syndrome were immunized against Streptococcus pneumoniae . All vaccinated patients had detectable serum antibodies against measles, mumps, rubella, varicella, hepatitis B, H . influenzae, and S . pneumoniae . There were 3 infections despite vaccination; 1 patient developed varicella after RTPL and 1 patient on PD had 2 episodes of peritonitis caused by H . influenzae and S . pneumoniae . In conclusion, monitoring and administration of the vaccines by the renal team enabled a high immunization rate . Whether vaccines, as documented by antibody titers, or by the low prevalence in the general population promoted the low prevalence of infections remains open, as there were at least a few vaccination failures.

Infect Immun, 2002 Sep, 70(9), 5279 - 82
Functional domain of bovine milk lactoferrin which inhibits the adherence of Streptococcus mutans cells to a salivary film; Oho T et al.; The bovine lactoferrin molecule and relatively long lactoferrin fragments containing residues 473 to 538 strongly inhibited adherence of Streptococcus mutans to saliva-coated hydroxyapatite beads . Each cysteine residue in Lf411 (residues 473 to 538) was replaced by a serine residue, and the mutants Lf411-C481S and Lf411-C532S strongly inhibited S . mutans adherence . These results suggest that the functional domain of lactoferrin that binds to a salivary film lies in residues 473 to 538 and that the region might be concealed by disulfide bond formation between Cys481 and Cys532 in the Lf411 fragment.

Infect Immun, 2002 Sep, 70(9), 5091 - 5
The human polymeric immunoglobulin receptor facilitates invasion of epithelial cells by Streptococcus pneumoniae in a strain-specific and cell type-specific manner; Brock SC et al.; Streptococcus pneumoniae is a gram-positive bacterial pathogen that causes invasive life-threatening disease worldwide . This organism also commonly colonizes the upper respiratory epithelium in an asymptomatic fashion . To invade, this pathogen must traverse the respiratory epithelial barrier, allowing it to cause disease locally or disseminate hematogenously throughout the body . Previous work has demonstrated that S . pneumoniae choline-binding protein A, a pneumococcal surface protein, interacts specifically with the human polymeric immunoglobulin receptor, which is expressed by cells in the respiratory epithelium . Choline-binding protein A is required for efficient colonization of the nasopharynx in vivo . Additionally, a recent study showed that the R6x laboratory strain of S . pneumoniae invades a human pharyngeal cell line in a human polymeric immunoglobulin receptor-dependent manner . These findings raised the possibility that the interaction between choline-binding protein A and human polymeric immunoglobulin receptor may be a key determinant of S . pneumoniae pathogenesis . However, the strain used in prior invasion studies, R6x, is an unencapsulated, nonpathogenic strain . In the present study we determined the relative ability of strain R6x or pathogenic strains to invade a variety of human polymeric immunoglobulin receptor-expressing epithelial cell lines . The results of this work suggest that human polymeric immunoglobulin receptor-dependent enhanced invasion of epithelial cells by S . pneumoniae is a limited phenomenon that occurs in a strain-specific and cell type-specific manner.

Infect Immun, 2002 Sep, 70(9), 5086 - 90
Analysis of serum cross-reactivity and cross-protection elicited by immunization with DNA vaccines against Streptococcus pneumoniae expressing PspA fragments from different clades; Miyaji EN et al.; Streptococcus pneumoniae is a major cause of disease, especially in developing countries, and cost-effective alternatives to the currently licensed vaccines are needed . We constructed DNA vaccines based on pneumococcal surface protein A (PspA), an antigen shown to induce protection against pneumococcal bacteremia . PspA fragments can be divided into three families, which can be subdivided into six clades, on the basis of PspA amino acid sequence divergence (S . K . Hollingshead, R . Becker, and D . E . Briles, Infect . Immun . 68:5889-5900, 2000) . Since most clinical isolates belong to family 1 or family 2, PspA fragments from members of both of these families were analyzed . Vectors encoding the complete N-terminal regions of PspAs elicited significant humoral responses, and cross-reactivity was mainly restricted to the same family . DNA vaccines encoding fusions between PspA fragments from family 1 and family 2 were also constructed and were able to broaden the cross-reactivity, with induction of antibodies that showed reactions with members of both families . At least for the pneumococcal strains tested, the cross-reactivity of antibodies was not reflected in cross-protection . Animals immunized with DNA vaccines expressing the complete N-terminal regions of PspA fragments were protected only against intraperitoneal challenge with a strain expressing PspA from the same clade.

Infect Immun, 2002 Sep, 70(9), 5019 - 25
Pneumococcal infections in humans are associated with increased apoptosis and trafficking of type 1 cytokine-producing T cells; Kemp K et al.; Streptococcus pneumoniae infections are associated with considerable morbidity and mortality throughout the world . The immunopathology is characterized by an intense inflammatory reaction, including a strong acute-phase response and increased numbers of neutrophils in the circulation . However, little is known regarding the T-cell response during in vivo infections in humans . The purpose of this study was to test the hypothesis that activated T cells producing type 1 cytokines were engaged in the host response to pneumococcal infections . The phenotype and function of T cells were studied in 22 patients at admission to a department of infectious diseases and after antibiotic treatment for 1 week compared with an age-matched, healthy control group . Pneumococcal infections induced lymphopenia in the circulation due to the disappearance of activated T lymphocytes with a type 1 cytokine profile . In contrast, the numbers of naive T cells and interleukin-4-producing T cells did not change . Activated type 1 cytokine-producing cells reappeared in the circulation in relation to the treatment and clinical improvement . The underlying mechanisms during infection may include sequestration in the peripheral tissues and/or apoptosis . In fact, increased activation-induced apoptosis in the remaining peripheral lymphocytes and elevated levels of soluble Fas ligand were detected at admission to the hospital . In conclusion, these data suggest that activated T lymphocytes with a type 1 cytokine profile are highly engaged in the in vivo immune response to S . pneumoniae.

Infect Immun, 2002 Sep, 70(9), 4977 - 86
Structure-function relationships for human antibodies to pneumococcal capsular polysaccharide from transgenic mice with human immunoglobulin Loci; Chang Q et al.; To investigate the influence of antibody structure and specificity on antibody efficacy against Streptococcus pneumoniae, human monospecific antibodies (MAbs) to serotype 3 pneumococcal capsular polysaccharide (PPS-3) were generated from transgenic mice reconstituted with human immunoglobulin loci (XenoMouse mice) vaccinated with a PPS-3-tetanus toxoid conjugate and their molecular genetic structures, epitope specificities, and protective efficacies in normal and complement-deficient mice were determined . Nucleic acid sequence analysis of three MAbs (A7, 1A2, and 7C5) revealed that they use two different V(H)3 genes (A7 and 1A2 both use V3-15) and three different V(kappa) gene segments . The MAbs were found to have similar affinities for PPS-3 but different epitope specificities and CDR3 regions . Both A7 and 7C5 had a lysine at the V(H)-D junction, whereas 1A2 had a threonine . Challenge experiments with serotype 3 S . pneumoniae in BALB/c mice revealed that both 10- and 1- micro g doses of A7 and 7C5 were protective, while only a 10- micro g dose of 1A2 was protective . Both A7 and 7C5 were also protective in mice lacking either an intact alternative (FB(-/-)) or classical (C4(-/-)) complement pathway, but 1A2 was not protective in either strain . Our data suggest that PPS-3 consists of epitopes that can elicit both highly protective and less protective antibodies and that the superior efficacies of certain antibodies may be a function of their structures and/or specificities . Further investigation of relationships between structure, specificity, and efficacy for defined MAbs to PPS may identify antibody features that might be useful surrogates for antibody (and vaccine) efficacy.

Infect Immun, 2002 Sep, 70(9), 4968 - 76
The regulator PerR is involved in oxidative stress response and iron homeostasis and is necessary for full virulence of Streptococcus pyogenes; Ricci S et al.; Ferric uptake regulator (Fur) and Fur-like proteins form an important family of transcriptional regulators in many bacterial species . In this work we have characterized a Fur-like protein, the peroxide regulator PerR, in an M1 serotype of Streptococcus pyogenes . To determine the role of PerR in S . pyogenes, we inactivated the gene by allelic replacement . PerR-deficient bacteria showed 48% reduction of (55)Fe incorporation from the culture medium . Transcriptional analysis revealed that mtsA, encoding a metal-binding protein of an ABC transporter in S . pyogenes, was transcribed at lower levels than were wild-type cells . Although total iron accumulation was reduced, the growth of the mutant strain was not significantly hampered . The mutant showed hyperresistance to hydrogen peroxide, and this response was induced in wild-type cells by growth in aerobiosis, suggesting that PerR acts as an oxidative stress-responsive repressor . PerR may also participate in the response to superoxide stress, as the perR mutant was more sensitive to the superoxide anion and had a reduced transcription of sodA, which encodes the sole superoxide dismutase of S . pyogenes . Complementation of the mutation with a functional perR gene restored (55)Fe incorporation, response to peroxide stress, and transcription of both mtsA and sodA to levels comparable to those of wild-type bacteria . Finally, the perR mutant was attenuated in virulence in a murine air sac model of infection (P < 0.05) . These results demonstrate that PerR is involved in the regulation of iron homeostasis and oxidative stress responses and that it contributes to the virulence of S . pyogenes.

Infect Immun, 2002 Sep, 70(9), 4897 - 901
Protection from group B streptococcal infection in neonatal mice by maternal immunization with recombinant Sip protein; Martin D et al.; The protective potential of antibodies directed against group B streptococcus (GBS) Sip surface protein was determined by using the mouse neonatal infection model . Rabbit Sip-specific antibodies administered passively to pregnant mice protected their pups against a GBS lethal challenge . In addition, active immunization with purified recombinant Sip protein of female CD-1 mice induced the production of specific antibodies that also confer protection to the newborn pups against GBS strains of serotypes Ia/c, Ib, II, III, and V . These data confirm that Sip-specific antibodies can cross the placenta and conferred protective immunity against GBS infections.

Infect Immun, 2002 Sep, 70(9), 4859 - 69
Involvement of Lsp, a member of the LraI-lipoprotein family in Streptococcus pyogenes, in eukaryotic cell adhesion and internalization; Elsner A et al.; Three open reading frames (ORFs) were identified by a genome walking strategy in the genomes of serotype M49 group A streptococcal (GAS) strains CS101 and 591 . These ORFs were located between the mga core regulon and the dipeptide permease operon . The deduced amino acid (aa) sequences contained signature sequences indicative of a lipoprotein (306 aa), an intracellular protein (823 aa), and a secreted peptide (66 aa), respectively . ORF1 (named Lsp for lipoprotein of Streptococcus pyogenes) and ORF2 exhibited a high degree of homology to the lmb/ORF2 genes of S . agalactiae (B . Spellerberg et al., Infect . Immun . 67:871-878, 1999) . The three ORFs were found to be present in each of the 27 GAS serotype strains tested . Transcription analysis revealed a polycistronic lsp/ORF2 and a monocistronic ORF3 message that were detected primarily at the transition from exponential to stationary growth phase . lsp and ORF2 mutants, ORF2- and ORF3-luciferase reporter fusions, and antiserum against recombinant Lsp were produced to examine the biological role of these genes . Although high Zn(2+) and Cu(2+) ion concentrations decreased lsp operon expression, Lsp did not transport divalent cations as described for other LraI-type operons . The lsp mutant had reduced fibronectin binding . Although no direct binding of Lsp to fibronectin could be demonstrated, the lsp mutant showed decreased transcription of prtF2 encoding the fibronectin-binding protein F2 . Both the lsp and ORF2 mutants showed decreased laminin binding . Adherence to and internalization into A549 epithelial cells of both mutants was reduced without a detectable effect on eukaryotic cell viability . The transcription of a number of virulence factors was altered in the lsp mutants and ORF2 mutants . The changes in laminin binding and eukaryotic cell internalization could be explained by changes in transcription of speB (cysteine protease) and/or the global regulators mga, csrRS, and nra.

Antimicrob Agents Chemother, 2002 Sep, 46(9), 3094 - 5
Comparative activities of the oxazolidinone AZD2563 and linezolid against selected recent North American isolates of Streptococcus pneumoniae; Baum SE et al.; The activity of AZD2563 against 250 highly resistant pneumococci and 267 drug-susceptible isolates was determined . The AZD2563 MICs for 50 and 90% of the strains tested were 1 and 2 micro g/ml and 0.5 and 1 micro g/ml, respectively, for the two isolate groups . These MICs were within 1 log(2) dilution of those of linezolid.

Antimicrob Agents Chemother, 2002 Sep, 46(9), 2990 - 5
Pharmacodynamic assessment of ertapenem (MK-0826) against Streptococcus pneumoniae in a murine neutropenic thigh infection model; Xuan D et al.; The objective of this study was to determine the susceptibility breakpoint of a new carbapenem, ertapenem (MK-0826), against Streptococcus pneumoniae strains based on bacterial density and survival studies in a murine thigh infection model . Sixteen S . pneumoniae isolates for which MICs ranged from 0.015 to 4.0 mg/liter were tested with neutropenic ICR mice . Animals were infected with bacteria at 10(5) to 10(6) CFU per thigh and were treated with ertapenem starting at 2 h postinfection for 4 days . Ertapenem was given subcutaneously at 50 mg/kg of body weight every 6 h, which simulates the human pharmacodynamic profile (in particular, the duration of time that the concentration of free drug remains above the MIC of 2 mg/liter) . At 0 and 24 h postinfection, thighs were harvested for bacterial density determination . Survival was assessed during 4 days of therapy and 3 days after the therapy . A protein binding study was conducted with mice by use of the ultrafiltration method . Protein binding in mice was approximately 95%, which is comparable to that in humans . The average change in bacterial density ranged from -0.22 to -4.4 log CFU per thigh over 24 h compared to 0-h controls . The extent of microbial eradication was dependent on the MIC for the S . pneumoniae isolate . Substantial bactericidal activities (i.e., killing of approximately 2 log CFU per thigh) were consistently observed against isolates for which MICs were <or=2 mg/liter, which also resulted in nearly 100% survival during the 4 days of drug dosing and 3 days after the therapy . Less-pronounced and highly variable bactericidal activities were detected against isolates for which the MIC was 4 mg/liter . Substantial enhancement in bactericidal activity was observed for CBA/J mice and is attributed to the contribution of the host defenses in the immunocompetent species . Assessment of the effectiveness of ertapenem by bacterial-density reduction over 24 h and by survival over 4 days of therapy in the murine thigh infection model reveals that the drug maintains maximal efficacy against S . pneumoniae isolates for which the MIC of this agent is <or=2 mg/liter.

Antimicrob Agents Chemother, 2002 Sep, 46(9), 2963 - 8
Antistreptococcal activity of telithromycin compared with seven other drugs in relation to macrolide resistance mechanisms in Russia; Kozlov RS et al.; The susceptibilities of 468 recent Russian clinical Streptococcus pneumoniae isolates and 600 Streptococcus pyogenes isolates, from 14 centers in Russia, to telithromycin, erythromycin, azithromycin, clarithromycin, clindamycin, levofloxacin, quinupristin-dalfopristin, and penicillin G were tested . Penicillin-nonsusceptible S . pneumoniae strains were rare except in Siberia, where their prevalence rate was 13.5%: most were penicillin intermediate, but for three strains (two from Smolensk and one from Novosibirsk) the MICs of penicillin G were 4 or 8 micro g/ml . Overall, 2.5% of S . pneumoniae isolates were resistant to erythromycin . Efflux was the prevalent resistance mechanism (five strains; 41.7%), followed by ribosomal methylation encoded by constitutive erm(B), which was found in four isolates . Ribosomal mutation was the mechanism of macrolide resistance in three isolates; one erythromycin-resistant S . pneumoniae isolate had an A2059G mutation in 23S rRNA, and two isolates had substitution of GTG by TPS at positions 69 to 71 in ribosomal protein L4 . All S . pyogenes isolates were susceptible to penicillin, and 11% were erythromycin resistant . Ribosomal methylation was the most common resistance mechanism for S . pyogenes (89.4%) . These methylases were encoded by erm(A) {subclass erm(TR)} genes, and their expression was inducible in 96.6% of isolates . The rest of the erythromycin-resistant Russian S . pyogenes isolates (7.6%) had an efflux resistance mechanism . Telithromycin was active against 100% of pneumococci and 99.2% of S . pyogenes, and levofloxacin and quinupristin-dalfopristin were active against all isolates of both species.

Pediatr Infect Dis J, 2002 Jun, 21(6), 589 - 91; discussion 613-4
Management of pneumococcal meningitis; Kaplan SL; During the past decade antibiotic resistance among Streptococcus pneumoniae isolates has complicated the empiric approach to and treatment of pneumococcal meningitis . Standard empiric therapy for suspected bacterial meningitis for infants and children older than 1 month of age is the combination of cefotaxime or ceftriaxone and vancomycin . Treatment is modified after antimicrobial susceptibilities are available . The optimal treatment of pneumococcal meningitis caused by strains with a cefotaxime/ceftriaxone MIC >2 microg/ml is unknown, although the addition of rifampin to the initial combination is generally recommended . The role of newer agents including quinolones is under investigation . Dexamethasone remains the only adjunctive antiinflammatory therapy to consider . The empiric approach to the child with suspected bacterial meningitis who has received the pneumococcal conjugate vaccine currently remains unchanged.

Pediatr Infect Dis J, 2002 Jun, 21(6), 567 - 8
Breast milk transmission of group B streptococcal infection; Dinger J et al.; A term female infant developed late onset group B streptococcal disease on Day 12 of life . 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 underrecognized cause of neonatal infection.

Clin Ther, 2002 Jul, 24(7), 1134 - 47
Randomized, double-blind, multicenter comparison of oral cefditoren 200 or 400 mg BID with either cefuroxime 250 mg BID or cefadroxil 500 mg BID for the treatment of uncomplicated skin and skin-structure infections; Bucko AD et al.; BACKGROUND: Uncomplicated skin and skin-structure infections are commonly observed in medical practice . Because these infections typically are confined to the superficial layers and seldom lead to the destruction of skin structures and resultant systemic dissemination, in general they can be treated with an oral antibiotic with potent microbiologic activity against gram-positive pathogens . OBJECTIVE: This paper compares the efficacy and tolerability of 3 beta-lactam antibiotics in patients with uncomplicated skin and skin-structure infections . METHODS: Two double-blind, multicenter, parallel-group studies were conducted, in which patients aged > or = 12 years with uncomplicated skin and skin-structure infections were randomized to receive cefditoren 200 or 400 mg, cefuroxime 250 mg, or cefadroxil 500 mg, each BID for 10 days . Study 1 compared cefditoren with cefuroxime; Study 2 compared cefditoren with cefadroxil . Clinical and microbiologic responses were assessed at a posttreatment visit (within 48 hours of treatment completion) and test-of-cure visit (7-14 days after treatment completion) . Patients were monitored closely throughout the study with the use of physical examinations, clinical laboratory tests, and assessment of adverse events . RESULTS: A total of 1,685 patients (855 males, 830 females; mean age, 41.1 years {range, 12-95 years}) were enrolled . Within both studies, the 3 treatment groups were similar at baseline based on demographic characteristics and types of infection . Cellulitis (26%), wound infection (25%), and simple abscess (15%) were the most common infections . Clinical cure rates at the test-of-cure visit were 85% (443/523) for cefditoren 200 mg, 83% (427/516) for cefditoren 400 mg, 88% (234/265) for cefuroxime, and 85% (211/248) for cefadroxil . At the test-of-cure visit, cefditoren 200 mg had eradicated significantly fewer of the causative pathogens isolated before treatment in microbiologically evaluable patients than did cefuroxime in Study 1 (P = 0.043) but significantly more of the pathogens than did cefadroxil in Study 2 (P = 0.018) . Eradication rates for the most commonly isolated pathogens were generally similar in the 3 treatment groups in both studies, with the only significant difference favoring cefditoren 200 and 400 mg over cefadroxil for Peptostreptococcus species in Study 2 (P = 0.016 and P = 0.003, respectively) . A minority of patients (< or = 5% in any treatment group) discontinued study-drug treatment prematurely due to a treatment-related adverse event, with statistically higher rates for cefditoren 400 mg than for cefditoren 200 mg and the comparator cephalosporins (each P < 0.05) . All 3 cephalosporins were generally well tolerated . Most adverse events (>93%) were categorized as mild to moderate, with the most common being diarrhea, nausea, and headache . CONCLUSION: In this population of patients with uncomplicated skin and skin-structure infections, including those due to Staphylococcus aureus or Streptococcus pyogenes, the clinical cure rate and tolerability of cefditoren were comparable to those of cefuroxime and cefadroxil.

Eur J Biochem, 2002 Aug, 269(16), 4121 - 33
Unfolding and aggregation during the thermal denaturation of streptokinase; Azuaga AI et al.; The thermal denaturation of streptokinase from Streptococcus equisimilis (SK) together with that of a set of fragments encompassing each of its three domains has been investigated using differential scanning calorimetry (DSC) . Analysis of the effects of pH, sample concentration and heating rates on the DSC thermograms has allowed us to find conditions where thermal unfolding occurs unequivocally under equilibrium . Under these conditions, pH 7.0 and a sample concentration of less than approximately 1.5 mg x mL(-1), or pH 8.0, the heat capacity curves of intact SK can be quantitatively described by three independent two-state transitions, each of which compares well with the two-state transition observed for the corresponding isolated SK domain . The results indicate that each structural domain of SK behaves as a single cooperative unfolding unit under equilibrium conditions . At pH 7.0 and high sample concentration, or at pH 6.0 at any concentration investigated, the thermal unfolding of domain A was accompanied by the time-dependent formation of aggregates of SK . This produces a severe deformation of the DSC curves, which become concentration dependent and kinetically controlled, and thus precludes their proper analysis by standard deconvolution methods . A simple model involving time-dependent, high-order aggregation may account for the observed effects . Limited-proteolysis experiments suggest that in the aggregates the N-terminal segment 1-63 and the whole of SK domain C are at least partially structured, while domain B is highly unstructured . Unfolding of domain A, under conditions where the N-terminal segment 1-63 has a high propensity for beta sheet structure and a partially formed hydrophobic core, gives rise to rapid aggregation . It is likely that this region is able to act as a nucleus for the aggregation of the full-length protein.

Eur J Biochem, 2002 Aug, 269(16), 3969 - 77
In vitro and in vivo self-cleavage of Streptococcus pneumoniae signal peptidase I; Zheng F et al.; We have previously demonstrated that Streptococcus pneumoniae signal peptidase (SPase) I catalyzes a self-cleavage to result in a truncated product, SPase37-204 {Peng, S.B., Wang, L., Moomaw, J., Peery, R.B., Sun, P.M., Johnson, R.B., Lu, J., Treadway, P., Skatrud, P.L . & Wang, Q.M . (2001) J . Bacteriol.183, 621-627} . In this study, we investigated the effect of phospholipid on invitro self-cleavage of S . pneumoniae SPase I . In the presence of phospholipid, the self-cleavage predominantly occurred at one cleavage site between Gly36-His37, whereas the self-cleavage occurred at multiple sites in the absence of phospholipid, and two additional self-cleavage sites, Ala65-His66 and Ala143-Phe144, were identified . All three self-cleavage sites strongly resemble the signal peptide cleavage site and follow the (-1, -3) rule for SPase I recognition . Kinetic analysis demonstrated that self-cleavage is a concentration dependent and intermolecular event, and the activity in the presence of phospholipid is 25-fold higher than that in the absence of phospholipid . Biochemical analysis demonstrated that SPase37-204, the major product of the self-cleavage totally lost activity to cleave its substrates, indicating that the self-cleavage resulted in the inactivation of the enzyme . More importantly, the self-cleavage was demonstrated to be happening in vivo in all the growth phases of S . pneumoniae cells . The bacterial cells keep the active SPase I at the highest level in exponential growth phase, suggesting that the self-cleavage may play an important role in regulating the activity of the enzyme under different conditions.

Lett Appl Microbiol, 2002, 35(3), 237 - 41
Association of pyrogenic exotoxin genes with pharyngitis and rheumatic fever/rheumatic heart disease among Indian isolates of Streptococcus pyogenes; Nandi S et al.; AIM: To monitor the presence of various pyrogenic exotoxin genes in strains of Streptococcus pyogenes isolated in India . METHODS & RESULTS: Isolates recovered from pharyngitis (52) and rheumatic fever (RF)/ rheumatic heart disease (RHD) (8) patients were analysed for the presence of toxin genes, speA, speB and speF, by PCR . The specificity of the products was confirmed by restriction enzyme digestion and Southern hybridization . Among the 60 isolates studied, the incidence of speA, speB and speF were 5(8.3%), 56(93.3%) and 53(88.3%), respectively . The expression of these genes was established in representative isolates by RT-PCR . CONCLUSIONS: Comparative analysis of frequency of the speA, speB and speF genes, among pharyngitis and RF/RHD associated isolates, showed higher incidence in RF/RHD (25%, 100%,100%) as compared to pharyngitis patients (5.8%, 92.3%, 86.5%), respectively . SIGNIFICANCE OF STUDY: The presence of the speA gene, which is usually associated with scarlet fever or toxic shock-like syndrome, within few Indian isolates may be indicative of new virulent strains circulating within the Indian community . High distribution of toxin genes among RF/RHD compared to pharyngitis isolates indicate their possible role in increased virulence.

Lett Appl Microbiol, 2002, 35(3), 223 - 7
Analysis of a dextran-binding domain of the dextranase of Streptococcus mutans; Morisaki H et al.; AIMS: To examine the dextran-binding domain of the dextranase (Dex) of Streptococcus mutans . METHODS AND RESULTS: Deletion mutants of the Dex gene of Strep . mutans were prepared by polymerase chain reaction and expressed in Escherichia coli cells . Binding of the truncated Dexs to dextran was measured with a Sephadex G-150 gel . Although the Dexs which lacked the N-terminal variable region lost enzyme activity, they still retained dextran-binding ability . In addition, further deletion into the conserved region from the N-terminal did not influence the dextran-binding ability . However, the Dex which carried a deletion in the C-terminus still possessed both enzyme activity and dextran-binding ability . Further deletion into the conserved region from the C-terminal resulted in complete disappearance of both enzyme and dextran-binding activities . CONCLUSIONS: Deletion analysis of the Dex gene of Strep . mutans showed that the C-terminal side (about 120 amino acid residues) of the conserved region of the Dex was essential for dextran-binding ability . SIGNIFICANCE AND IMPACT OF THE STUDY: The dextran-binding domain was present in a different area from the catalytic site in the conserved region of the Dex molecule . The amino acid sequence of the dextran-binding domain of the Dex differed from those of glucan-binding regions of other glucan-binding proteins reported.

Med Oncol, 2002, 19(2), 71 - 8
Cancer patients undergoing chemotherapy show adequate serological response to vaccinations against influenza virus and Streptococcus pneumoniae; Nordoy T et al.; Cancer patients receiving chemotherapy are prone to develop infections that might postpone treatment and lead to complications . The aim of our study was to investigate whether a heterogeneous population of patients with solid tumors and malignant lymphoma undergoing chemotherapy would respond serologically to vaccination against influenza and pneumococcal disease . There are no established routines in oncology departments in Norway regarding vaccination of these patients . The study included 35 cancer patients with median age 53 yr (range 20-74) and 38 controls with median age 57 yr (range 43-75) . The chemotherapy regimens used were mild or moderately immunosuppressive . After one vaccination, 25 patients (72%) and 34 controls (87%) were serologically protected against two or three influenza strains . A higher proportion of patients with solid tumors (81%) than lymphoma (38%) achieved protection . Age, months on chemotherapy, and curative versus palliative treatment did not influence responses to vaccination . After vaccination with a 23-valent polysaccharide vaccine against pneumococci, most patients and controls achieved protective serum levels of antibodies against the different serotypes, with the exception that fewer patients were protected against serotype 4 . The responses in controls were, however, generally stronger to all serotypes . Tumor type did not influence this vaccination response . We conclude that our cancer patients achieved adequate responses to influenza virus and Streptococcus pneumoniae . These are not live vaccines and are therefore safe for immunocompromised patients . Routine vaccinations against influenza virus and Streptococcus pneumoniae should be considered in cancer patients undergoing mild to moderately immunosuppressive chemotherapy.

Curr Microbiol, 2002 Sep, 45(3), 155 - 60
The ketolide antibiotic ABT-773 is a specific inhibitor of translation and 50S ribosomal subunit formation in Streptococcus pneumoniae cells; Champney WS et al.; ABT-773 is a new 3-keto macrolide antibiotic that has been shown to be very effective against infections by Gram-positive microorganisms . This work examines its inhibitory effects in cells of Streptococcus pneumoniae . ABT-773 caused a proportional decline in cell growth rates and viability with an IC(50) of 5 ng/ml . Protein synthesis in these cells was reduced by 50% at an antibiotic concentration of 2.5 ng/ml . This compound was also found to be a very effective inhibitor of the formation of the 50S ribosomal subunit in growing cells . Pulse and chase labeling assays revealed a reduced rate of 50S synthesis in antibiotic-treated cells . At 2 ng/ml, the rate was reduced to 33% of the control synthesis rate . An IC(50) of 5 ng/ml was found for the effect on this process, indicating an equal effect of the drug on translation and assembly . Synthesis of the 30S ribosomal subunit was unaffected by this antibiotic . The effects of ABT-773 in S . pneumoniae are compared with those of the related ketolide antibiotic telithromycin in S . pneumoniae and in Staphylococcus aureus.

Int J Pediatr Otorhinolaryngol, 2002 Sep 2, 65(2), 117 - 23
Prevalence and antimicrobial-resistance of S . pneumoniae and S . pyogenes in healthy children in the region of Madrid; Herruzo R et al.; Streptococcus pneumoniae and Streptococcus pyogenes are common agents of respiratory or ORL pathology . Pneumococcus sensitivity has progressively decreased to penicillin and other antimicrobial agents, mainly in south of Europe, but this resistance report can be erroneous by a selection bias, because they sampled only hospital cases . OBJECTIVES: To determine the prevalence, antimicrobial susceptibility and risk factors of S . pneumoniae and S . pyogenes in healthy children under 5 years of age who go to infant school . SUBJECT AND METHODS: Cross sectional study in six infant schools . An epidemiological inquiry (risk factors of carrier state) was filled out and a nasopharyngeal specimen was taken from each child, S . pneumoniae and S . pyogenes were identified and antimicrobial tests were performed . RESULTS: We have studied 156 children with a mean age of 2.24 (standard deviation (S.D.), 0.85) and 58% have been treated with antibiotic in the last 3 months . The prevalence of S . pneumoniae or S . pyogenes were 12.2 and 5.1%, respectively . S . pyogenes only was isolated in two schools . Age was associated with S . pyogenes carrier but the rest of studied factors have no statistical significance with both microorganisms . All the S . pneumoniae showed resistance to one or more antibiotic (mainly to clavunate-amoxycillin: 94.7%), while S . pyogenes only was resistant to clavunate-amoxycillin . CONCLUSION: Healthy children (0-4 years) with antibiotherapy in last 3 months have a great frequency of resistant S . pneumoniae . It is necessary to reduce the antibiotic use at home (Medical education) .

Bull Tokyo Dent Coll, 2002 May, 43(2), 75 - 82
Effect of molecular mass and degree of deacetylation of chitosan on adsorption of Streptococcus sobrinus 6715 to saliva treated hydroxyapatite; Sano H et al.; We evaluated the influence of molecular mass and degree of deacetylation of chitosan on the adsorption of Streptococcus sobrinus 6715 to saliva-treated hydroxyapatite (S-HA) by measuring the optical density of the bacterial cell suspensions released from saliva-treated hydroxyapatite . Twenty-five chitosan samples with different molecular masses (0.8-6 kDa) and degrees of deacetylation (10-95%) were prepared for the study . We found that the inhibition of adsorption of S . sobrinus 6715 to S-HA correlated positively with the molecular mass of chitosan (R = 0.876) and that the optimal degree of deacetylation was 50-60% for maximum inhibition of bacterial binding to S-HA . We also examined the effect of chitosan on zeta potentials of the oral bacteria and their surface hydrophobicities . It was observed that chitosan reduced the magnitude of the zeta potential and surface hydrophobicities of the oral bacteria . Thus, the results demonstrated that chitosan with a molecular mass of 5-6 kDa and a degree of deacetylation of 50-60% might have the potential to act as an effective anti-plaque agent because of its polycationic properties.

Genetika, 2002 Jul, 38(7), 911 - 5
{Regulation of transcription in the system of genes responsible for bacteriocins production in Streptococcus equi }; Kotel'nikova EA et al.; Bacteriocin production in many Gram-positive bacteria is controlled by a two-component regulatory system that is composed of the sensor protein and the response regulator . In this work, methods of computer analysis were used to describe the locus of genes responsible for the synthesis of class II bacteriocins in the Streptococcus equi genome . Potential regulatory sites (direct repeats) recognized by a DNA-binding protein of the corresponding two-component system were predicted.

Saudi Med J, 2002 Jul, 23(7), 793 - 6
Profile of childhood meningitis in a hospital in South West Saudi Arabia; Al-Binali AM et al.; OBJECTIVE: To study the pattern of meningitis in children admitted to King Faisal Military Hospital, Aseer region, Kingdom of Saudi Arabia, during the period 1987 to 2000 . Particular emphasis was on Hemophilus influenzae meningitis . METHODS: All the patients between the age of one month and 13 years of age, who were diagnosed with meningitis during that period, using the International Classification of Disease 9 coding system, were included in this study . RESULTS: A total of 43 cases of meningitis based on the cerebrospinal fluid results were found . The majority (74%) of these cases were less than 2 years of age . Twenty-four patients had a positive cerebrospinal fluid culture . Fifteen of them (62.5%) were due to Hemophilus influenzae . The others were due to Streptococcus pneumoniae, Klebsiella pneumoniae, Staphylococcus aureus and group B Streptococcus . The remaining 19 patients had cerebrospinal fluid findings consistent with bacterial meningitis CONCLUSION: Meningitis due to Hemophilus influenzae, constitutes a large percentage of childhood meningitis in the Kingdom of Saudi Arabia . This increase is highly attributed to the lack of vaccination against this organism . We recommend introducing this vaccine as a part of the routine vaccination schedule for all children.

Saudi Med J, 2002 Jul, 23(7), 782 - 5
Pyoderma among Hajj Pilgrims in Makkah; Fatani MI et al.; OBJECTIVE: Bacterial skin infections have been considered as a possible health problem of the Hajj pilgrims . Significant increase in the rate of resistance to commonly used antibiotics against gram positive organisms has been observed . The present study was planned to obtain the microbiological profile of bacterial skin infections and their susceptibility to antimicrobials . METHODS: Pyodermas were investigated clinically and bacteriologically by a prospective study conducted on patients attending the dermatology clinic at the King Faisal Hospital, Makkah, Kingdom of Saudi Arabia during 2 Hajj periods (2000 - 2001) . RESULTS: Of a total of 80 pyoderma patients, 52.5% were primary and 47.5% secondary . The leading cause of primary pyoderma was found to be impetigo in 28.8% cases, and of secondary pyoderma was infected eczema in 18.8% cases . Positive cultures were found in 87.5% cases . The organisms responsible for primary pyoderma were: Staphylococcus aureus (65.6%), Streptococcus pyogenes (28.1%) or both (6.4%) while in secondary pydermas were: Staphylococcus aureus (44.7%), Streptococcus pyogenes (15.8%), or both (18.4%), and gram negative bacilli (21.1%) . The resistant pattern of antimicrobials against Staphylococcus aureus was as follows: penicillin 80.85%, tetracycline 10.6%, gentamicin 6.4%, erythromycin 4.3% and cotrimaxazole 4.3% . Oxacillin and cephalothin were found least resistant (2.1%) . CONCLUSION: Pyoderma appeared as one of the common health hazard of our Hajj pilgrims . Penicillin and tetracycline are found ineffective in treating skin infections caused by Staphylococcus aureus while oxacillin is recommended as first line of treatment.

Int J Hyg Environ Health, 2002 Jul, 205(5), 385 - 92
Septic shock caused by Streptococcus suis: case report and investigation of a risk group; Strangmann E et al.; A case of septic shock caused by Streptococcus suis type 2 occurred in a 36-year-old truck driver who transported pigs . Here, as well as in nearly all other cases of S . suis infections reported to date, close occupational contact with pork or pigs preceded the incident . This epidemiological link may be explained by the frequent occurrence of S . suis as a commensal and opportunistic germ in pigs . In order to assess the potential risk for an infection with S . suis, 132 workers in pig slaughtering, pork dissecting and processing industries were examined in a cross sectional study for the occurrence of S . suis in their pharynx, and compared with an age and sex matched control group . The evaluation of the pharyngeal swabs showed an atypical colonisation by a variety of microorganisms in some of the employees who were so far healthy, but potentially at risk . The colonisation of the case group with S . suis amounted to 5.3%.

Clin Infect Dis, 2002 Sep 1, 35(5), 556 - 64 Epub 2002 Aug 09.
Failure of macrolide antibiotic treatment in patients with bacteremia due to erythromycin-resistant Streptococcus pneumoniae; Lonks JR et al.; The rate of macrolide resistance among Streptococcus pneumoniae is increasing, but some investigators have questioned its clinical relevance . We conducted a matched case-control study of patients with bacteremic pneumococcal infection at 4 hospitals to determine whether development of breakthrough bacteremia during macrolide treatment was related to macrolide susceptibility of the pneumococcal isolate . Case patients (n=86) were patients who had pneumococcal bacteremia and an isolate that was either resistant or intermediately resistant to erythromycin . Controls (n=141) were patients matched for age, sex, location, and year that bacteremia developed who had an erythromycin-susceptible pneumococcus isolated . Excluding patients with meningitis, 18 (24%) of 76 case patients and none of 136 matched controls were taking a macrolide when blood was obtained for culture (P=.00000012) . Moreover, 5 (24%) of 21 case patients with the low-level-resistant M phenotype and none of 40 controls were taking a macrolide (P=.00157) . These data show that development of breakthrough bacteremia during macrolide or azalide therapy is more likely to occur among patients infected with an erythromycin-resistant pneumococcus, and they also indicate that in vitro macrolide resistance resulting from both the efflux and methylase mechanisms is clinically relevant.

Sex Transm Dis, 2002 Aug, 29(8), 483 - 5
Invasive group a streptococcus associated with an intrauterine device and oral sex; Gisser JM et al.; BACKGROUND: Peritonitis due to group A Streptococcus (GAS) and toxic shock syndrome occurred in a previously healthy 45-year-old woman with an intrauterine device . The intrauterine device was believed to be the portal of entry . In addition, her husband was found to be an asymptomatic carrier of GAS in his oropharynx . GOAL: The goal was to increase physicians' awareness of oral sex as a risk factor for transmission of invasive GAS disease . STUDY DESIGN: This is a case report of the development of GAS peritonitis and toxic shock syndrome in a woman after acquisition of the organism through oral sex . RESULTS: The GAS strains isolated from the patient and her husband were identical in their M-type, T-type, and exotoxin gene pattern . CONCLUSION: Because the couple practices oral sex, it was postulated that this was the mode of transmission of the GAS.

Laryngoscope, 2002 Aug, 112(8 Pt 1), 1474 - 81
Myringotomy delays the tympanic membrane recovery in acute otitis media: a study in the rat model; Spratley J et al.; BACKGROUND/HYPOTHESIS: Acute otitis media is a major cause of visits to pediatric health care providers . Myringotomy in uncomplicated acute otitis media is debatable today . The study addressed this problem through the otomicroscopic and histopathological observations of the events occurring in the tympanic membrane during the first week after myringotomy . STUDY DESIGN: Randomized study in an experimental animal model . METHODS: Under anesthesia, the left middle ear of 36 Sprague-Dawley rats was inoculated with Streptococcus pneumoniae type 3 . Forty-eight hours later, at day 0, four animals were immediately killed and the remaining animals were randomly assigned into a myringotomy group (n = 16, myringotomy on the left ear) and a non-myringotomy group (n = 16, otomicroscopy without myringotomy) . Otomicroscopy and killings were performed in series of four animals from each group at days 1, 2, 4, and 7 after myringotomy . Tympanic membranes were collected after fixation and processed for light and electron microscopy . RESULTS: All inoculated ears showed a manifest acute otitis media at day 0 . An intense infiltration by inflammatory cells and edema distorted severely the tympanic membrane structure . These findings decreased the following days . However, inflammation as evaluated by the thickness and the cytoarchitecture of the tympanic membrane layers, recovered significantly faster in the membranes in the non-myringotomy group . At day 7, all tympanic membranes in the myringotomy group were closed by a hypertrophic keratinizing epithelium and a remodeling connective tissue layer, whereas the animals in the non-myringotomy group had a residual edema in the lamina propria . CONCLUSIONS: The present infectious model induced an intense inflammatory reaction within the entire structure of the tympanic membrane . Myringotomy provoked a delayed recovery from the inflammatory process within the tympanic membrane . Therefore, if applicable to human conditions, the use of myringotomy in the management of acute otitis media should be restricted to selected cases of acute otitis media.

BMJ . 2002 Aug 10;325(7359):308.
Risk factors for early onset neonatal group B streptococcal sepsis: case-control study; Oddie S et al.; OBJECTIVES: To quantify risk factors for and the prevalence of early onset group B streptococcal sepsis in neonates in a geographically defined population . DESIGN: Cases were collected prospectively for two years from April 1998 and compared with four controls each, matched for time and place of delivery . SETTING: The former Northern health region of the United Kingdom . PARTICIPANTS: Infants infected with group B streptococcus in the first week of life . RESULTS: The prevalence of early onset group B streptococcal sepsis was 0.57 per 1000 live births . Premature infants comprised 38% of all cases and 83% of the deaths . Prematurity (odds ratio 10.4, 95% confidence interval 3.9 to 27.6), rupture of the membranes more than 18 hours before delivery (25.8, 10.2 to 64.8), rupture of the membranes before the onset of labour (11.1, 4.8 to 25.9), and intrapartum fever (10.0, 2.4 to 40.8) were significant risk factors for infection . Had the interim recommendations on best practice issued by the Group B Streptococcus Working Group of the Public Health Laboratory Service been uniformly applied to the fetuses alive at the onset of labour, 29 of 37 (78%) might have been given antibiotic prophylaxis during labour . At least 23 of these 29 (79%) could have had antibiotics for four hours or more before delivery . To achieve this, 16% of all women would have been given antibiotics during labour . CONCLUSIONS: Early onset group B streptococcal sepsis remains an important problem in the United Kingdom . Prevention based on risk factors might reduce the prevalence at the cost of treating many women with risk factors . Using rupture of the membranes before the onset of labour as a risk factor might be expected to improve the success of guidelines for prophylaxis.

Biochem J, 2002 Nov 1, 367(Pt 3), 901 - 6
Mechanism by which metal cofactors control substrate specificity in pyrophosphatase; Zyryanov AB et al.; Family I soluble pyrophosphatases (PPases) exhibit appreciable ATPase activity in the presence of a number of transition metal ions, but not the physiological cofactor Mg(2+) . The results of the present study reveal a strong correlation between the catalytic efficiency of three family I PPases (from Saccharomyces cerevisiae, Escherichia coli and rat liver) and one family II PPase (from Streptococcus mutans ) in ATP and tripolyphosphate (P(3)) hydrolysis in the presence of Mg(2+), Mn(2+), Zn(2+) and Co(2+) on the one hand, and the phosphate-binding affinity of the enzyme subsite P2 that interacts with the electrophilic terminal phosphate group of ATP on the other . A similar correlation was observed in S . cerevisiae PPase variants with modified P1 and P2 subsites . The effect of the above metal ion cofactors on ATP binding to S . cerevisiae PPase paralleled their effect on phosphate binding, resulting in a low affinity of Mg-PPase to ATP . We conclude that PPase mainly binds ATP and P(3) through the terminal phosphate group that is attacked by water . Moreover, this interaction is critical in creating a reactive geometry at the P2 site with these bulky substrates, which do not otherwise fit the active site perfectly . We propose further that ATP is not hydrolysed by Mg-PPase, since its interaction with the terminal phosphate is not adequately strong for proper positioning of the nucleophile-electrophile pair.

Eur Respir J Suppl, 2002 Jul, 36, 40s - 53s
Treatment of community-acquired lower respiratory tract infections in adults; Ortqvist A; Community-acquired lower respiratory tract infection (LRTI) is a common cause of acute illness in adults . The spectrum of disease ranges from a mild mucosal colonisation or infection, acute bronchitis or acute exacerbation of chronic bronchitis/chronic obstructive pulmonary disease (AE-CB/COPD), to an overwhelming parenchymal infection with the patient presenting with severe community-acquired pneumonia (CAP) . Although the great majority of LRTIs are self-limiting viral infections, CAP is most often a bacterial disease with a substantial mortality . Thus, antibiotic treatment is rarely indicated for acute bronchitis and is only indicated for the more severe cases of AE-CB/COPD, but it is nearly always indicated for CAP, for which a delay in treatment may increase the risk of a fatal outcome . It may be difficult to differentiate between a viral and a bacterial LRTI, or between bronchitis/AE-CB/COPD and CAP . This may be one reason why antibiotics are prescribed to more than two-thirds of patients with LRTIs in Europe and the USA . Considering the worldwide development of antibiotic resistance, this is not an acceptable situation . Since an empirical approach is nearly always necessary in the management of LRTI, greater emphasis must be placed on the decision of whether or not to prescribe an antibiotic at all . This decision should be based on an assessment of the severity of the disease, including underlying risk factors, and on markers for bacterial/parenchymal/ invasive LRTI . The choice of empirical therapy must be based on the same data together with epidemiological information . The choice of antibiotic must always cover Streptococcus pneumoniae, which remains the main pathogen of morbidity and mortality in CAP . In hospital, attempts should be made to obtain an aetiological diagnosis in order to be able to switch to a specific treatment or to evaluate a failure of empirical therapy . Several guidelines for the management of community-acquired pneumonia have been published during the last 10 yrs . Some reports indicate that the implementation of such guidelines has resulted in lowered costs, length of stay in hospital and mortality . However, the results from these studies are not consistent and the evidence is still weak.

Eur Respir J Suppl, 2002 Jul, 36, 3s - 8s
Bacteriological evidence of antibiotic failure in pneumococcal lower respiratory tract infections; Klugman KP; The global pandemic of antimicrobial resistance, particularly in the pneumococcus, has had a major impact on the management of community-acquired pneumonia . A number of prospective and retrospective studies have analysed the impact of penicillin resistance on clinical outcome in pneumonia . Pharmacodynamic principles predicting success when the antibiotic dose exceeds the minimum inhibitory concentration (MIC) for 40-50% of the dosing interval have proved remarkably accurate . There is no evidence of bacteriological failure of penicillins active against resistant strains . There is a single report of the failure of the less active agent, ticarcillin . High dose oral and intravenous amoxicillin should treat strains with MICs < or = 4 microg x mL(-1), as should high doses of intravenous penicillin, ceftriaxone and cefotaxime . Strains of pneumococci resistant to these agents at an MIC > or = 8 microg x mL(-1) are rare at the present time . Most other cephalosporins are less active and should not be used empirically for drug-resistant Streptococcus pneumoniae . Bacteriological failures of cefazolin, cefuroxime and ceftazidime have been reported . There is increasing evidence of bacteriologically confirmed macrolide failure of pneumonia therapy at MICs > or = 4 microg x mL(-1) . The molecular basis of the resistance is irrelevant if the MIC is in that range or higher . Double mutants in the parC and gyrA genes lead to fluoroquinolone resistance that has been found to cause bacteriological failure of the fluoroquinolones, particularly levofloxacin and ciprofloxacin, in the management of pneumonia and exacerbations of chronic bronchitis . Two mutations in these genes can greatly increase the MICs of all the marketed fluoroquinolones, and raise the prospect of failure of therapy even with the more active ones . However, demonstration of bacteriological failure of gatifloxacin or moxifloxicin has not yet been reported . High dose, active beta-lactams or fluoroquinolones with enhanced activity against Gram positive pathogens remain the drugs of choice for the management of community-acquired pneumonia caused by the drug-resistant pneumococcus.

Eur Respir J Suppl, 2002 Jul, 36, 20s - 27s
Community-acquired pneumonia in Europe: causative pathogens and resistance patterns; Woodhead M; Community-acquired pneumonia (CAP) is a common condition affecting about 1/1,000 of the adult population per year . It occurs when bacteria enter the alveolar spaces of the lung initiating an inflammatory response which leads to the clinical features of cough, sputum production, breathlessness and sometimes chest pain and haemoptysis . At the end of the last century the causal relationship between bacteria and pneumonia was established and many of the early discoveries about the causes of CAP were made in Europe . Some 41 different prospective studies have established that approximately 10 different microbial pathogens regularly cause CAP with occasional cases due to other rarer causes . The frequency of these organisms in Europe is similar in most countries, but there are some geographic differences . Differences in frequency are also apparent according to illness severity . It is generally recognised that Streptococcus pneumoniae is the most important causal bacterium in all countries . A relatively recent development has been the appearance and spread, in some of the common causative bacteria, of resistance to commonly used antibiotics to which they were once sensitive . The frequency of such resistance does vary markedly between European countries . However, published data is often difficult to interpret . The reasons for this are that the frequency of resistance varies according to the age of the patient, the site of the sample, the clinical diagnosis, the use of prior antibiotics and the influence of special groups e.g . those with cystic fibrosis . The impact of in vitro antibiotic resistance on clinical outcome is still poorly understood, but recent studies are helping to clarify this issue and will be discussed.

Pathol Biol (Paris), 2002 Jul, 50(6), 374 - 9
{Role of pneumococcus in pediatric infectious pathology}; Bingen E; Streptococcus pneumoniae is the most common bacterial cause of invasive and non-invasive infections in children of less than two years . The high level of resistance to penicillin and other antimicrobial agents observed particularly in France is responsible of the difficulties concerning the treatment of acute otitis media and meningitis due to S . pneumoniae . Potential positive consequences of the implementation of pneumococcal conjugate vaccine may include prevention of invasive diseases and prevention of spread of the drug resistant-strains.

DNA Cell Biol, 2002 May-Jun, 21(5-6), 397 - 404
Host-parasite interactions in Staphylococcus aureus keratitis; Jett BD et al.; Ulcerative keratitis is among the leading ocular bacterial infections, and Streptococcus aureus accounts for approximately 25% of cases in some surveys . Although S . aureus expresses numerous virulence factors, many of which are under the control of staphylococcal global regulatory genes, their pathophysiologic roles in keratitis are largely unknown . Similarly, the nature of the host response during S . aureus keratitis is unclear . Following a review of previously published research on the pathophysiology of S . aureus ocular infection, we present the results of a study designed to assess the host-parasite relationship between S . aureus and human corneal epithelial cells (HCECs) in vitro . In this model system, a wild-type S . aureus strain and its isogenic mutants harboring mutations in agr and sar global regulatory genes or fibronectin-binding proteins A and B (fnbAB) were tested for their ability to bind and invade confluent HCEC monolayers . The contribution of host cell factors was assessed by preincubating HCECs with various inhibitory agents . These studies demonstrated that S . aureus not only adhered to the surface of HCECs but was also internalized, as has been previously observed in other nonocular cell lines . Adherence and invasion of HCECs was saturable at 1 h of incubation in the presence of approximately 10(7) CFU per HCEC monolayer (multiplicity of infection approximately 10) . A mutant defective in both agr and sar global regulators was not significantly different in invasive capacity compared to its isogenic wild-type parent strain . In contrast, mutations in fibronectin-binding proteins A and B (fnbAB) reduced the invasiveness of S . aureus by 99% compared to the wild-type strain . Pretreatment of HCECs with colchicine had little effect on S . aureus invasion . In sharp contrast, cytochalasin D and genistein were each capable of inhibiting invasion by >99% . In summary, the results of this study point to fibronectin-binding protein as a key S . aureus surface adhesin facilitating invasion of HCECs in vitro . Furthermore, these results suggest an active mechanism for S . aureus internalization by HCECs, likely involving actin polymerization and tyrosine kinase activity . Additional studies are warranted to determine the applicability of these findings in vivo, and to facilitate the rational design of therapeutic agents aimed at blocking the establishment and progression of S . aureus keratitis.

Clin Oral Investig, 2002 Jun, 6(2), 92 - 7
Chemical-biological interactions of NaF with three different cell lines and the caries pathogen Streptococcus sobrinus; Dogan S et al.; Fluoride is used in dentistry as a prophylactic agent to reduce caries rates due to the demineralization/remineralization effect and its influence on the metabolism of cariogenic bacteria . The purpose of this study was to evaluate the cytotoxic effects of sodium fluoride (NaF) on three different cell lines and the antibacterial potency on Streptococcus sobrinus . Cell lines were treated with various concentrations of NaF ranging from 0.039 mM to 10 mM for 24 h . For microbial assays, concentrations of NaF between 0.03 mM and 10 mM were added to liquid cultures of bacteria . Our results showed that immortalized human keratinocytes (HaCaT) and human osteogenic sarcoma cells (SAOS-2) were similarly affected by concentrations up to 2.5 mM . However, cell growth of HaCaT was slightly more inhibited at 2.5 mM of NaF than SAOS-2 . At concentrations between 0.62 mM and 10 mM, 3T3 mouse fibroblast cells reacted more sensitively than HaCaT and SAOS-2 to NaF . The 3T3 cells did not survive in the presence of 10 mM NaF . NaF caused no significant effect on all tested cells at concentrations of < or = 0.31 mM . NaF at 0.039 mM and 0.06 mM did not affect growth of S . sobrinus . At concentrations of 0.125 mM and 0.5 mM, growth was slightly reduced . The proliferation of S . sobrinus significantly decreased at 1 mM and 2 mM NaF . S . sobrinus survived at 4 mM, revealing a delayed log phase with a decreased proliferation . No viable S . sobrinus cells were detected at concentrations of > or = 8 mM NaF . Data analysis revealed that overall treatment effects were highly significant (P<0.05, analysis of variance, Tukey's difference test) . This study indicates that cytotoxic effects due to NaF significantly vary in dependence upon the applied cell line . The toxicity of NaF approached 50% (TC50) at concentrations of 6 mM for HaCaT, 2.3 mM for 3T3 cells, and 7.5 mM for SAOS-2 . Additionally, NaF revealed antimicrobial effects only at concentrations that are significantly higher than oral fluoride concentrations.

Pediatrics, 2002 Aug, 110(2 Pt 1), 371 - 6
Invasive pneumococcal disease and hemolytic uremic syndrome; Brandt J et al.; OBJECTIVE: Severe pneumococcal infections have been associated with hemolytic uremic syndrome (HUS), usually with a poor clinical outcome when compared with Escherichia coli O157 gastroenteritis-associated (D+) HUS . We examined our experience with 12 cases of Streptococcus pneumoniae-associated HUS (SP-HUS) and compare it with a cohort of diarrhea-associated HUS (D+ HUS) . METHODS: A retrospective case survey compared 2 unrelated groups of HUS patients . Demographic factors, clinical indices of disease severity, and outcome were used to compare the 2 groups of HUS patients . RESULTS: Twelve children with SP-HUS were studied . Pneumococcal pneumonia with empyema was the most common precipitating illness (67%), pneumococcal meningitis was present in 17% of children, pneumonia with bacteremia in 8%, and both pneumonia and meningitis in 8% . SP-HUS patients were younger than D+ HUS patients (22.1 vs 49 months) and had more severe renal and hematologic disease than D+ HUS patients . Compared with D+ HUS patients, SP-HUS patients were more likely to require dialysis (75% vs 59%) and had a longer duration of hospitalization (33.2 vs 16.1 days) and duration of thrombocytopenia (11.6 vs 6.8 days) . SP-HUS patients were also more likely to require platelet transfusions (83% vs 47%) and needed more platelet (4.7 vs 0.5) and packed red blood cell transfusions (7.8 vs 2.0) . The 2 groups did not differ significantly in the incidence of extrarenal HUS complications . There were no deaths in either group . Seven patients have been seen for long-term follow-up; 2 developed end-stage renal disease, and 5 have normal renal function . CONCLUSIONS: HUS is a rare but severe complication of invasive pneumococcal infection . Although disseminated intravascular coagulation can also occur in these children, the treatment and follow-up may be different in the 2 conditions . Children with pneumococcal disease and severe hematologic or renal abnormalities should be investigated for evidence of HUS.

J Immunol, 2002 Aug 15, 169(4), 2189 - 95
Streptococcus sanguis modulates type II collagen-induced arthritis in DBA/1J mice; Costalonga M et al.; Native type II collagen is tolerogenic when given orally or i.p . to DBA/1J mice and induces autoimmune arthritis when given s.c . in CFA . The tolerogenic epitope is contained in cyanogen bromide fragment 11 (CB11) and is structurally mimicked by PGEQGPK within the platelet aggregation-associated protein (PAAP) on Streptococcus sanguis . To learn whether S . sanguis modulates transmucosally the Ag-specific development of autoimmune arthritis, DBA/1J pups were given live S . sanguis, CB11, or type II collagen intragastrically . Feeding S . sanguis at 6 days postpartum delayed the onset of arthritis, and reduced the rate, final severity, and percentage of affected limbs . Next, PAAP(+) S . sanguis and type II collagen were tested for T cell cross-reactivity . T cells primed with the tolerogenic epitope of type II collagen proliferated more when incubated with PAAP(+) S . sanguis than with PAAP(-) Streptococcus gordonii or type II collagen, suggesting an Ag-specific transmucosal tolerogenic effect . In neonatal mice, therefore, bacterial surface Ags that mimic self can transmucosally stimulate Ag-specific inhibitory T cells . In adult mice immunized with type II collagen, these Ag-specific inhibitory T cells manifest later as attenuated arthritis . The PAAP(+) S . sanguis appear to activate adult memory, rather than naive, type II collagen-specific T cells, suggesting that systemic challenge with commensal self-mimicking microorganisms may perpetuate existing autoimmunity, but not initiate autorecognition.

J Biol Chem, 2002 Oct 18, 277(42), 39235 - 42 Epub 2002 Aug 05.
Characterization of the amino acids involved in substrate specificity of nonphosphorylating glyceraldehyde-3-phosphate dehydrogenase from Streptococcus mutans; Marchal S et al.; In order to address the molecular basis of the specificity of aldehyde dehydrogenase for aldehyde substrates, enzymatic characterization of the glyceraldehyde 3-phosphate (G3P) binding site of non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase (GAPN) from Streptococcus mutans has been undertaken . In this work, residues Arg-124, Tyr-170, Arg-301, and Arg-459 were changed by site-directed mutagenesis and the catalytic properties of GAPN mutants investigated . Changing Tyr-170 into phenylalanine induces no major effect on k(cat) and K(m) for d-G3P in both acylation and deacylation steps . Substitutions of Arg-124 and Arg-301 by leucine and Arg-459 by isoleucine led to distinct effects on K(m), on k(cat), or on both . The rate-limiting step of the R124L GAPN remains deacylation . Pre-steady-state analysis and substrate isotope measurements show that hydride transfer remains rate-determining in acylation . Only the apparent affinity for d-G3P is decreased in both acylation and deacylation steps . Substitution of Arg-459 by isoleucine leads to a drastic effect on the catalytic efficiency by a factor of 10(5) . With this R459L GAPN, the rate-limiting step is prior to hydride transfer, and the K(m) of d-G3P is increased by at least 2 orders of magnitude . Binding of NADP leads to a time-dependent formation of a charge transfer transition at 333 nm between the pyridinium ring of NADP and the thiolate of Cys-302, which is not observed with the holo-wild type . Accessibility of Cys-302 is shown to be strongly decreased within the holostructure . The substitution of Arg-301 by leucine leads to an even more drastic effect with a change of the rate-limiting step similar to that observed for R459I GAPN . Taking into account the three-dimensional structure of GAPN from S . mutans and the data of the present study, it is proposed that 1) Tyr-170 is not essential for the catalytic event, 2) Arg-124 is only involved in stabilizing d-G3P binding via an interaction with the C-3 phosphate, and 3) Arg-301 and Arg-459 participate not only in d-G3P binding via interaction with C-3 phosphate but also in positioning efficiently d-G3P relative to Cys-302 within the ternary complex GAPN.NADP.d-G3P.

Eur J Pharmacol, 2002 Aug 2, 449(1-2), 177 - 81
Pneumococcal meningitis in the rat: evaluation of peroxynitrite scavengers for adjunctive therapy; Kastenbauer S et al.; We evaluated the effect of different peroxynitrite scavengers for adjunctive therapy of experimental bacterial meningitis . Twenty hours after intracisternal injection of Streptococcus pneumoniae, rats were treated with ceftriaxone {100 mg/kg intraperitoneal (i.p.)} and either urate (300 mg/kg i.p.), Mn(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP, 15 mg/kg i.p.), ascorbate (100 mg/kg i.p.), or urate (300 mg/kg i.p.) + ascorbate (100 mg/kg i.p.) . Six hours after initiation of treatment, the cerebrospinal fluid (CSF) pleocytosis was significantly (p<0.05) reduced by urate (8697 +/- 1526 cells/microl) and MnTBAP (8542 +/- 4059 cells/microl) vs . ceftriaxone alone (15,793 +/- 3202 cells/microl) . Brain concentrations of proinflammatory cytokines {interleukin-1beta (IL-beta), interleukin-6 (IL-6), and macrophage inflammatory protein-2 (MIP-2)} were also reduced by urate and MnTBAP . The intracranial hypertension was significantly reduced by MnTBAP (14.0 +/- 5.4 mm Hg), but not by urate (25.5 +/- 7.1 mm Hg) vs . ceftriaxone alone (22.5 +/- 5.9 mm Hg) . Ascorbate alone had no effect on CSF pleocytosis (15,775 +/- 7058 cells/microl), intracranial pressure (25.6 +/- 8.8 mm Hg), and brain cytokine concentrations . However, the combination of urate and ascorbate was as effective as MnTBAP (CSF pleocytosis: 5392 +/- 4232 cells/microl, intracranial pressure: 13.3 +/- 6.9 mm Hg).

J Anim Sci, 2002 Jul, 80(7), 1977 - 85
Effects of bacterial direct-fed microbials on ruminal fermentation, blood variables, and the microbial populations of feedlot cattle; Ghorbani GR et al.; A study was conducted to determine whether bacterial direct-fed microbials (DFM) could be used to minimize the risk of acidosis in feedlot cattle receiving high concentrate diets . Six ruminally cannulated steers, previously adapted to a high concentrate diet, were used in a double 3 x 3 Latin square to study the effects of DFM on feed intake, ruminal pH, and ruminal and blood characteristics . Steers were provided ad libitum access to a diet containing steam-rolled barley, barley silage, and a protein-mineral supplement at 87, 9, and 4% (DM basis), respectively . Treatments were as follows: control, Propionibacterium P15 (P15), and Propionibacterium P15 and Enterococcus faecium EF212 (PE) . The bacterial treatments (10(9) cfu/g) plus whey powder carrier, or whey powder alone for control, were top-dressed once daily at the time of feeding (10 g/{steer/d}) . Periods consisted of 2 wk of adaptation and 1 wk of measurements . Ruminal pH was continuously measured for 6 d using indwelling electrodes . Dry matter intake and ruminal pH (mean, minimum, hours, and area pH < 5.8 or < 5.5) were not affected by treatment (P > 0.05) . However, supplementation with P15 increased protozoal numbers (P < 0.05) with a concomitant increase in ruminal NH3 concentration (P < 0.01) and a decrease in the number of amylolytic bacteria (P < 0.05) compared with the control . Streptococcus bovis, enumerated using a selective medium, was numerically reduced with supplementation of PE . Although blood pH and blood glucose were not affected by DFM supplementation, steers fed PE had numerically lower concentrations of blood CO2 than control steers, which is consistent with a reduced risk of metabolic acidosis . Although the bacterial DFM used in this study did not induce changes in DMI or ruminal and blood pH, some rumen and blood variables indicated that the bacterial DFM used in this study may decrease the risk of acidosis in feedlot cattle.

Korean J Ophthalmol, 2002 Jun, 16(1), 59 - 61
A case of streptococcus pyogenes endophthalmitis following cataract surgery; Kim YH et al.; A small number of cases of bacterial endophthalmitis due to Streptococcus pyogenes, a Gram positive organism, have previously been reported . In this case, rapidly progressive Streptococcus pyogenes endophthalmitis was developed five years after cataract surgery which had been . The previous cataract surgery was combined with intraocular lens implantation by trans-scleral suspension technique . Treatment included enucleation and intravenous antibiotic injection . In this case of delayed Streptococcus pyogenes endophthalmitis after extracapsular cataract extraction . It seems probable that progressive erosion of the suture material resulted in exogenous endophthalmitis.

J Dent Res, 2002 Jul, 81(7), 505 - 10
Novel sucrose-dependent adhesion co-factors in Streptococcus mutans; Tao L et al.; Streptococcus mutans glucosyltransferases form extracellular glucans from sucrose to promote adhesion to the teeth . We tested whether additional factors are involved in S . mutans sucrose-dependent adhesion . By screening a pVA891-insertion mutant library of S . mutans LT11, we isolated four clones deficient in adhesion to glass in the presence of sucrose, but normal in glucosyltransferase activities . The genetic loci flanking the insertion sites were retrieved and identified . They encode glycerol-3-phosphate dehydrogenase, an ABC transporter, a multidrug-efflux pump, and either the ribulose monophosphate operon or ascorbate metabolism operon . The four mutants were analyzed for their phenotypic expression and in vivo colonization in rats . The multidrug efflux pump mutant failed to colonize the rats . Three other mutants colonized the rats by reverting to the wild type . Therefore, these four factors may contribute to S . mutans sucrose-dependent adhesion.

J Antimicrob Chemother, 2002 Aug, 50(2), 201 - 9
Antimicrobial susceptibility of Streptococcus suis isolated from swine in France and from humans in different countries between 1996 and 2000; Marie J et al.; The susceptibility of 135 Streptococcus suis strains isolated from pigs (n = 110) and from humans (n = 25) to 13 antimicrobial agents was studied by microdilution and disc diffusion methods using Mueller-Hinton Agar II (MH) supplemented with either defibrinated sheep blood (MHSB) or horse serum (MHHS) . Results were similar for both methods used except for penicillin G whose zone diameters were reduced with MHSB compared with MHHS . When MH was supplemented with sheep blood, 39% of S . suis strains classified as penicillin susceptible by MHHS microdilution showed intermediate susceptibility . Nearly all strains were susceptible to penicillin G (except by disc diffusion in MHSB), amoxicillin, ceftiofur, florfenicol, gentamicin and bacitracin . The least active antimicrobial agents were doxycycline and macrolides/lincosamides . High-level resistance (MIC > 500 mg/L or zone diameters < 10 mm) to streptomycin and kanamycin was detected in only a few strains . The virulence of strains did not seem to be related to antimicrobial resistance because no statistical difference was reported between the proportion of resistant strains of S . suis isolated from pigs with meningitis, septicaemia and arthritis, and those from tonsils and nasal cavities . However, significant differences were found in the proportions of macrolide- or doxycycline-resistant strains between S . suis serotype 2 and other serotypes . The results of antibiotic susceptibility testing presented in this study indicate that beta-lactams can be used in empirical treatment of human and pig S . suis infections in France.

J Neuroimmunol, 2002 Aug, 129(1-2), 168 - 77
Antibodies to neuron-specific antigens in children with autism: possible cross-reaction with encephalitogenic proteins from milk, Chlamydia pneumoniae and Streptococcus group A; Vojdani A et al.; We measured autoantibodies against nine different neuron-specific antigens and three cross-reactive peptides in the sera of autistic subjects and healthy controls by means of enzyme-linked immunosorbent assay (ELISA) testing . The antigens were myelin basic protein (MBP), myelin-associated glycoprotein (MAG), ganglioside (GM1), sulfatide (SULF), chondroitin sulfate (CONSO4), myelin oligodendrocyte glycoprotein (MOG), alpha,beta-crystallin (alpha,beta-CRYS), neurofilament proteins (NAFP), tubulin and three cross-reactive peptides, Chlamydia pneumoniae (CPP), streptococcal M protein (STM6P) and milk butyrophilin (BTN) . Autistic children showed the highest levels of IgG, IgM and IgA antibodies against all neurologic antigens as well as the three cross-reactive peptides . These antibodies are specific because immune absorption demonstrated that only neuron-specific antigens or their cross-reactive epitopes could significantly reduce antibody levels . These antibodies may have been synthesized as a result of an alteration in the blood-brain barrier . This barrier promotes access of preexisting T-cells and central nervous system antigens to immunocompetent cells, which may start a vicious cycle . These results suggest a mechanism by which bacterial infections and milk antigens may modulate autoimmune responses in autism.

Scand J Infect Dis, 2002, 34(6), 468 - 71
Clinical characteristics of necrotizing fasciitis caused by group G Streptococcus: case report and review of the literature; Sharma M et al.; A 52-y-old diabetic male developed severe necrotizing fasciitis due to group G Streptococcus . A review of the English language literature revealed 8 additional cases . The mean age of the total of 9 cases was 65.5 y (range: 49-80 y) and the majority (n = 5; 55.6%) had no comorbid conditions . The duration of symptoms prior to presentation was 1-5 d (mean +/- SD = 2.5 +/- 1.5 d) . Presenting manifestations were swelling with redness (6/6 cases; 100%), severe pain (5/6 cases; 83.3%) and blister formation (3/6 cases; 50%); blisters developed eventually in 5/6 (88.3%) patients . Muscle involvement was noted in 2 patients (22.2%) . Progression to toxic shock-like syndrome occurred in 3 cases (33.3%) . The organism was isolated from the involved sites in all cases . Bacteremia was documented in 1/3 patients . Treatment included antibiotics (n = 9) and varying degrees of surgical debridement (n = 8) . The mortality rate was 33.3%; all patients who died developed toxic shock-like syndrome . These findings illustrate that, similar to Streptococcus pyogenes-induced fasciitis, necrotizing fasciitis due to group G Streptococcus can be severe and life-threatening . Early diagnosis, immediate surgical debridement and antibiotic therapy are essential in order to improve the outcome.

Scand J Infect Dis, 2002, 34(6), 407 - 12
Antibody to streptococcal cysteine proteinase as a seromarker of group A Streptococcal (Streptococcus pyogenes) infections; Batsford S et al.; Serological tests are commonly employed to aid the diagnosis of Streptococcus pyogenes infections, particularly when non-suppurative sequelae are suspected . Conventional laboratory practice is to measure antibody levels to various combinations of the extracellular group A Streptococcus (GAS) antigens streptolysin O (SLO), DNase B, streptokinase and hyaluronidase . Antibody to the extracellular cysteine proteinase streptococcal pyrogenic exotoxin B (SPE B) and its precursor zymogen is also produced in response to GAS infections . An indirect hemagglutination test for antibody to zymogen/SPE B was established and evaluated in serum samples from 168 patients with proven (n = 27) or suspected GAS (n = 141) infections, which were also screened for antibodies using the 4 conventional tests . For comparison, sera from 56 patients infected with a variety of other pathogens, as well as sera from 16 patients infected with either S . agalactiae or S . pneumoniae and 34 sera from healthy subjects, were tested . Statistical analysis confirmed that antibody to zymogen/SPE B is a serological marker that can discriminate GAS infections . It can be ranked with the anti-SLO titer, currently the most widely used test, as a marker of an antecedent GAS infection.

Scand J Infect Dis, 2002, 34(6), 403 - 6
Serum cytokine level during continuous venovenous hemofiltration in toxic shock-like syndrome due to group G beta Streptococcus bacteremia in a patient with idiopathic thrombocytopenic purpura; Takagi K et al.; We report a case of toxic shock-like syndrome due to a rare infection of group G Streptococcus bacteremia in a patient with idiopathic thrombocytopenic purpura and its successful treatment with continuous venovenous hemofiltration (CVVH) . As the result of sepsis treatment with CVVH, in addition to administration of vasopressors and antibiotics, serum levels of interleukin-1beta, interleukin-10 and tumor necrosis factor-a fell and shock was controlled.

Am J Psychiatry, 2002 Aug, 159(8), 1430 - 2
D8/17 expression on B lymphocytes in anorexia nervosa; Sokol MS et al.; OBJECTIVE: The authors' goal was to determine whether D8/17, a rheumatic fever susceptibility trait marker, identifies a possible type of anorexia nervosa: pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS) anorexia nervosa . METHOD: Using immunofluorescence, the authors measured the percentage of D8/17-positive B lymphocytes in the peripheral blood of 16 subjects 7-21 years old who had not had rheumatic fever but who had possible PANDAS anorexia nervosa . The comparison subjects were 17 psychiatric patients with no eating disorder and no PANDAS characteristics . Subjects were considered D8/17 positive if they had 12% or more D8/17+ cells . RESULTS: There were more D8/17-positive individuals among those with PANDAS anorexia nervosa (81%) than among the comparison subjects (12%) . The subjects with PANDAS anorexia nervosa had a higher percentage of D8/17+ cells (mean=27.1%, SD=17%) than the comparison subjects (mean=5.3%, SD=7.4%) . CONCLUSIONS: A larger study is needed to determine whether D8/17 serves as a marker for susceptibility to a type of anorexia nervosa.

Undersea Hyperb Med, 2001 Fall, 28(4), 181 - 6
Effect of hyperbaric oxygen and penicillin in a murine model of streptococcal myositis; Oztas E et al.; We investigated the effect of hyperbaric oxygen (HBO2) and penicillin therapy in a murine model of group A streptococcal myositis . The thighs of mice were inoculated with Streptococcus pyogenes . Four groups were evaluated: 1) control (n = 13), 2) HBO2 treatment (n = 15), 3) penicillin treatment (n = 12), and 4) penicillin and HBO2 treatment (n = 13) . Histologic methods were utilized to prove the existence of myositis and histologic changes in tissues following experimental intramuscular inoculation of mice with Streptococcus pyogenes . Mortality (day of death) and the number of colony forming units (cfu) were measured . Microscopic sections of the left thighs revealed extensive necrosis of muscle with acute inflammatory infiltrate in all groups . Penicillin significantly lowered cfu count in comparison to the control (P < 0.01) . Cfu's in group 4 were significantly lower than in group 3 (P < 0.01) . Survival was significantly longer in the penicillin group compared to the control (P < 0.01) . Survival in the combined treatment group was significantly longer than penicillin alone (P < 0.01) . These results suggest that 1) HBO2 treatment alone does not decrease mortality significantly in vivo, 2) penicillin therapy alone improves outcome significantly, and 3) the combined treatment of penicillin and HBO2 exerts synergistic effects in both decreasing bacterial counts in vivo and increasing survival in this model.

EMBO Rep, 2002 Aug, 3(8), 728 - 34
New approaches towards the identification of antibiotic and vaccine targets in Streptococcus pneumoniae; Di Guilmi AM et al.; Streptococcus pneumoniae causes more than one million deaths every year, mostly of young children in developing countries, due to pneumonia, bacteremia and meningitis . The emergence and dissemination of drug-resistant pneumococcal strains, coupled to changing patterns of virulence and the inadequacy of available vaccines, calls for an aggressive search for novel targets for antibiotic and vaccine development . Microbial genomics techniques allow genetic and biochemical tools to be employed to tackle discovery, design and development of new anti-infective agents based on the identification of hundreds of new targets . In this review, novel approaches employed to identify potential antibiotic and vaccine targets in S . pneumoniae are highlighted . Recently identified virulence factors, as well as molecules essential for bacterial viability, cell wall integrity and infectivity, are discussed.

Curr Womens Health Rep, 2002 Aug, 2(4), 238 - 44
Screening and management protocols for group B streptococcus in pregnancy; Carey JC; Infection with Group B streptococcus (Streptococcus agalactiae) (GBS) is a leading cause of neonatal morbidity and mortality . Screening by antepartum cultures or by risk factors and intrapartum antibiotics has been shown to reduce the risk of early onset GBS disease in newborns, but controversy exists about the best approach for screening and treatment . Currently recommended protocols do not prevent all cases of early onset GBS disease . Intrapartum antibiotics are not without harm, and currently recommended protocols will result in large numbers of women being treated who would not have benefited from treatment . In this article, we review the advantages and disadvantages of currently recommended protocols.

J Infect, 2002 Feb, 44 Suppl A, 11 - 6
Will resistance to ketolides develop in Streptococcus pneumoniae?
Leclercq R.
Recent data from surveillance studies suggest that levels of resistance to macrolide, lincosamide and streptograminB (MLSB) antibacterials in respiratory tract pathogens, particularly Streptococcus pneumoniae, are rising and limiting the usefulness of these drugs . New agents that do not select for resistance are essential to safeguard the future of antibacterial efficacy . The ketolides, of which telithromycin is the first to be registered for clinical use, represent a new class of antibacterials developed specifically for optimal empirical treatment of respiratory tract infections (RTIs) . Although derived chemically from macrolides, the ketolides, which possess innovative structural modifications, form a unique class in the macrolide family . A keto function at position 3 of the erythronolide A ring replaces the L-cladinose moiety, generating a class of compounds that, unlike 14- and 15-membered ring macrolides, will not induce MLSB resistance in vitro . A large aromatic N-substituted C11,12-carbamate side chain allows a more effective interaction with domain II of the 23S rRNA, enhancing binding to bacterial ribosomes and allowing binding to MLSB-resistant ribosomes . This novel structure allows ketolides to exert intrinsic activity against respiratory tract pathogens, avoid induction of MLSB resistance, and retain activity against MLS(B)-resistant strains . Furthermore, ketolides have a low potential to select for resistance and cross-resistance both in vitro and in vivo, making them an attractive option for the empirical treatment of RTIs.

J Am Board Fam Pract, 2002 Jul-Aug, 15(4), 261 - 5
Accuracy of rapid strep testing in patients who have had recent streptococcal pharyngitis; Sheeler RD et al.; BACKGROUND: Some clinicians have questioned the accuracy of rapid diagnosis of group A streptococcal pharyngitis by commercial immunochemical antigen test kits in the setting of recent streptococcal pharyngitis, believing that the false-positive rate was increased because of presumed antigen persistence . METHODS: We studied 443 patients--211 cases--who had clinical pharyngitis diagnosed as group A beta-hemolytic streptococcus infection in the past 28 days and compared them with 232 control patients who had symptoms of pharyngitis but no recent diagnosis of streptococcal pharyngitis . Our aim was narrowly focused to compare the rapid strep test with the culture method we used in our clinical practice . RESULTS: We found that the rapid strep test in this setting showed no difference in specificity (0.96 vs 0.98); hence, the assertion that rapid antigen testing had higher false-positive rates in those with recent infection was not confirmed . We also found that in patients who had recent streptococcal pharyngitis, the rapid strep test appears to be more reliable (0.91 vs 0.70, P < .001) than in those patients who had not had recent streptococcal pharyngitis . CONCLUSIONS: The findings of this study indicate that the rapid strep test is both sensitive and specific in the setting of recent group A beta-hemolytic streptococcal pharyngitis, and its use might allow earlier treatment in this subgroup of patients.

Pediatr Infect Dis J, 2002 May, 21(5), 393 - 9
Defining the potential impact of conjugate bacterial polysaccharide-protein vaccines in reducing the burden of pneumonia in human immunodeficiency virus type 1-infected and -uninfected children; Madhi SA et al.; BACKGROUND: The evaluation of bacterial conjugate vaccines in preventing pneumonia requires the definition of suitable outcome measures against which their use can be evaluated . One such possible outcome measure is alveolar consolidation confirmed by chest radiograph (CXR) . OBJECTIVE: To define the CXR presentation in relation to identified bacterial and respiratory viral pathogens among HIV-1-infected and -uninfected children . METHODS: The CXRs of 1186 of 1434 children hospitalized with severe lower respiratory tract infection were evaluated for the presence of alveolar consolidation (homogenous airspace infiltrate), bronchopneumonia (patchy airspace consolidation) or other CXR findings . Children were also investigated for bacterial infection by blood culture in 1364 of 1434 episodes and for respiratory viruses in 990 of 1434 episodes by immunofluorescein monoclonal antibody assays . RESULTS: The prevalence of HIV-1 infection among children who had CXRs in the study was 527 (46.2%) of 1142 . Alveolar consolidation was more common in HIV-1-infected (63.7%) than in HIV-uninfected children (42.4%, P < 10(-5)) whereas bronchopneumonic changes (29.0% vs . 38.0%, P = 0.001) or a normal CXR occurred in 7.0 vs . 18.2% (P < 10(-5)) of HIV-1-infected and -uninfected children, respectively . Alveolar consolidation was the main CXR presentation in HIV-1-infected (78.6%) and HIV-uninfected children (64.9%, P = 0.14) with all-cause bacteremic pneumonia as well as those with bacteremic Streptococcus pneumoniae pneumonia (76.9% vs . 83.3%, respectively; P = 0.99) . Respiratory virus-associated lower respiratory tract infection, however, was more likely to present with alveolar consolidation in HIV-1-infected (55.8%) than in HIV-uninfected (36.1%, P = 0.02) children . CONCLUSION: Although alveolar consolidation may be a useful tool in defining both the efficacy and burden of bacterial pneumonia in HIV-1-uninfected children, this may not be so for HIV-1-infected children . The higher occurrence of respiratory virus-associated alveolar consolidation, possibly coupled with Pneumocystis carinii pneumonia, may be significant confounders in the interpretation of CXR in HIV-1-infected children, limiting the use of alveolar consolidation as an outcome measure when evaluating the efficacy of bacterial conjugate vaccines in HIV-1-infected children.

J Clin Microbiol, 2002 Aug, 40(8), 2994 - 8
Phenotypic and genetic diversity of invasive pneumococcal isolates recovered from French children; Doit C et al.; We investigated the phenotypic and genetic diversity (by ribotyping) of Streptococcus pneumoniae isolates recovered from French children, by blood culture from meningitis-free patients (n = 244) and by cerebrospinal fluid culture from patients with meningitis (n = 154) . Isolates belonging to serotypes associated with carriage and penicillin-resistant isolates were significantly more frequent in children under 2 years of age than in older children . The seven-valent pneumococcal conjugate vaccine covered 68% of strains associated with bacteremia and 61% of strains associated with meningitis in children under 2 years . Although some serotypes were recovered more frequently from children with bacteremia than from those with meningitis, no difference in the genetic backgrounds of the two groups of strains was found.

J Clin Microbiol, 2002 Aug, 40(8), 2959 - 63
Pharmacoepidemiological analysis of provincial differences between consumption of macrolides and rates of erythromycin resistance among Streptococcus pyogenes isolates in Spain; Garcia-Rey C et al.; The M phenotype is by far the most common mechanism of erythromycin resistance among Streptococcus pyogenes isolates in Spain . A geographic analysis of the relationship between within-country differences in the prevalence of M-type resistance to erythromycin in S . pyogenes and the level of consumption of 14- and 15-membered macrolides within different provinces was carried out . From 1998 to 1999, a nationwide multicenter surveillance study yielded 2,039 consecutive pharyngeal isolates of S . pyogenes . Data on antibiotic consumption for the same period were gathered from IMS Health, and the corresponding daily defined doses per 1,000 inhabitants per day were calculated according to the Anatomic Therapeutic Classification index . Macrolide use was subdivided into dosages given three times a day (TID), twice a day (BID), or once a day (OD) . Spearman nonparametric correlation coefficients (R) were calculated, and variables proving to be significantly associated (P < 0.1) were introduced into a linear regression model . The total consumption of macrolides presented a significant correlation with the prevalence of resistance (R = 0.527; P = 0.032) . Neither TID nor BID macrolide consumption showed significant correlations . Only OD consumption had a significance below 0.1 . These data are consistent with the hypothesis that only the total consumption of macrolides influences the local rates of M-type erythromycin resistance in S . pyogenes, and subgroups of macrolides seem to have an additive rather than a selective effect by contributing to increasing the final amount of macrolides used . Local variations in total consumption were associated only with BID consumption (R = 0.849; P = 0.004) . The simple linear regression with total macrolide consumption showed a considerable determination coefficient (R(2) = 0.678; P = 0.006) . The model explains up to 68% of the measured variation and is clearly better as a predictor of the prevalence of resistance than the mere mean is . By solving the regression equation, the resultant value of 2.2 defined doses per 1,000 inhabitants per day fits with the existence of a critical threshold of selective pressure.

J Clin Microbiol, 2002 Aug, 40(8), 2922 - 9
Multiplex PCR assays for simultaneous detection of six major serotypes and two virulence-associated phenotypes of Streptococcus suis in tonsillar specimens from pigs; Wisselink HJ et al.; Multiplex PCR assays for the detection and identification of various Streptococcus suis strains in tonsillar specimens from pigs were developed and evaluated . In two separate reactions, five distinct DNA targets were amplified . Three targets, based on the S . suis capsular polysaccharide (cps) genes specific for serotypes 1 (and 14), 7, and 9, were amplified in multiplex PCR I . Two other targets, based on the serotype 2- (and 1/2-) specific cps gene and the epf gene, encoding the EF proteins of virulent serotype 2 and highly virulent serotype 1 strains, were amplified in multiplex PCR II . To identify false-negative results, firefly luciferase (luc) DNA and primers based on the luc gene were included in the assay . The multiplex PCR assays were evaluated with tonsillar specimens from pigs infected with S . suis strains . The results obtained with the PCR assays were compared with the results obtained with a bacteriological examination . Most (94%) of the results obtained with multiplex PCR assays were confirmed by the bacteriological examination . The PCR method seems to be more sensitive compared to the bacteriological method, since the remaining 6% of the samples were positive by PCR and negative by bacteriological examination . These results indicate that the PCR method is highly specific for the detection of S . suis strains most frequently involved in clinical disease in infected pig herds . The serotypes found by PCR in tonsillar specimens from diseased pigs were compared with the serotypes of the strains isolated from the affected tissues of the same pigs . The results showed that there is significant association between carriership and clinical illness for S . suis serotype 9 and EF-positive serotype 2 strains and not for serotype 7 and EF-negative serotype 2 (or 1/2) strains.

J Clin Microbiol, 2002 Aug, 40(8), 2913 - 8
Identification of Streptococcus bovis biotype I strains among S . bovis clinical isolates by PCR; Songy WB et al.; Streptococcus bovis causes 24% of all streptococcal infective endocarditis cases . There are many reports linking both S . bovis bacteremia and endocarditis with various forms of gastrointestinal disease (primarily colonic cancers) . S . bovis is divided into two biotypes: I and II . The biotype I strain is much more frequently isolated from patients with endocarditis, gastrointestinal disease, or both . We describe here the isolation of biotype I-specific DNA sequences and the development of a PCR test which can identify S . bovis biotype I strains among S . bovis clinical isolates.

Int J Syst Evol Microbiol, 2002 Jul, 52(Pt 4), 1247 - 55
Taxonomic dissection of the Streptococcus bovis group by analysis of manganese-dependent superoxide dismutase gene (sodA) sequences: reclassification of 'Streptococcus infantarius subsp . coli' as Streptococcus lutetiensis sp . nov . and of Streptococcus bovis biotype 11.2 as Streptococcus pasteurianus sp . nov; Poyart C et al.; The taxonomic dissection of the Streptococcus bovis-Streptococcus equinus group was carried out upon obtaining sequences for the manganese-dependent superoxide dismutase gene (sodA) of the type strains of S . bovis, Streptococcus caprinus, S . equinus, Streptococcus gallolyticus, Streptococcus infantarius, Streptococcus macedonicus and Streptococcus waius . The sodA sequences of 29 streptococcal strains of animal and human origin that were related to S . bovis were also sequenced . A phylogenetic analysis of the sodA sequences revealed that the S . bovis-S . equinus group comprises five different clusters that correspond to five distinct species . The type strains of S . bovis and S . equinus were associated in the same cluster, corresponding to the species S . equinus . The type strains of S . caprinus, S . gallolyticus, S . macedonicus and S . waius were associated in the same cluster, which defined a single species containing S . gallolyticus and its junior synonym S . caprinus, and S . macedonicus and its junior synonym S . waius . The two subspecies thought to constitute the species S . infantarius, namely S . infantarius subsp . infantarius and 'S . infantarius subsp . coli', were located in two distinct clusters . One of these clusters defined the species S . infantarius and included the type strain of S . infantarius subsp . infantarius . The other cluster defined 'S . infantarius subsp . coli', leading to the proposal of its reclassification as the novel species Streptococcus lutetiensis (NEM 782T = CIP 106849T) . The remaining cluster comprised all of the strains previously identified as belonging to S . bovis biotype 11.2, leading to the proposal to reassign these strains to the novel species Streptococcus pasteurianus (NEM 1202T = CIP 107122T) . The results of the phylogenetic analysis were confirmed by DNA-DNA hybridization experiments, thus demonstrating that sequence databases of defined DNA targets, such as sodA, may constitute a valuable alternative approach for modern bacterial systematics.

Int J Syst Evol Microbiol, 2002 Jul, 52(Pt 4), 1161 - 4
Streptococcus gallinaceus sp . nov., from chickens; Collins MD et al.; Three isolates of an unknown Gram-positive, catalase-negative, chain-forming, coccus-shaped organism isolated from an outbreak of septicaemia in a flock of adult broiler parents were characterized by phenotypic and molecular taxonomic methods . Comparative 16S rRNA gene sequencing studies demonstrated that the bacterium represents a new subline within the genus Streptococcus, related to, albeit distinct from, Streptococcus acidominimus, Streptococcus ovis, Streptococcus suis and close relatives . The unknown bacterium was readily distinguished from all recognized streptococcal species by biochemical tests . Based on phylogenetic and phenotypic evidence, it is proposed that the unknown bacterium from chickens be classified as Streptococcus gallinaceus sp . nov . The type strain is CCUG 42692T (= CIP 107087T).

Presse Med, 2002 Jun 15, 31(21 Pt 2), S5 - 10
{New microbiological data on the susceptibility of Pneumococci to levofloxacin}; Soussy CJ; INCREASINGLY WIDESPREAD USE OF THE NEW FLUOROQUINOLONES: For the treatment of airway infections raises the risk of bacterial resistance, particularly for Streptococcus pneumoniae . IN FRANCE, PRESCRIPTIONS FOR QUINOLONES: Are much less frequent than in several other large countries . This is also true for anti-pneumococcal fluoroquinolones although prescriptions have increased moderately over the last year . FURTHER TO THE CONCERNS RESULTING: From the publication of two studies from Canada and Hong Kong in 1999 that suggested an increasing rate of fluoroquinolone resistant pneumocci, it has been established that the real rate of isolation of resistant strains remains very low, particularly in France, while the rate of penicillin and macrolide resistant strains has been more than 50% in most studies . S . PNEUMONIAE RESISTANCE: Basically results from chromosomal mutations that inhibit the affinity of fluoroquinolones for intrabacterial targets (topoisomerase i.v . and gyrase DNA), or increase active exflux . ALTHOUGH THE CURRENT OUTLOOK IS RATHER OPTIMISTIC: It is nevertheless indispensable to implement preventive measures for prescriptions and personal health care in order to limit the emergence and dissemination of fluoroquinolone-resistant penumococcal strains.

J Dairy Sci, 2002 Jun, 85(6), 1468 - 75
Field validation of a milk line sampling device for monitoring milk quality and udder health; Godden S et al.; The objective of this study was to investigate the ability of a milk line sampling device to obtain a representative sample by comparing SCC and bacterial culture results between milk line and bulk tank samples for milk harvested from the same group of cows at the same milking . A total of 42 paired milk line and bulk tank samples were collected at separate milking events from 21 different herds . Concordance correlation coefficients showed a high level of agreement between the two sample types, with values ranging between 0.74 and 0.99 for all parameters and bacterial species measured . ANOVA showed that SCC and bacterial culture results for Streptococcus agalactiae, Staphylococcus aureus, Streptococcus non-agalactiae, Coliforms, and coagulase-negative staphylococci were neither numerically or statistically different between milk line and bulk tank samples . KAPPA analysis showed that overall agreement beyond chance between milk line and bulk tank samples in determining whether a herd was positive or negative for either Strep . agalactiae or Staph . aureus were 100 and 75%, respectively . While further research is needed to fully assess the utility of this tool for the purpose of bacterial culture, the results of this study suggest that the strategy of milk line sampling is a very promising monitoring tool . This sampling strategy should provide producers with inexpensive and timely information that will help to improve programs for monitoring milk quality and udder health in commercial dairy herds.

Clin Infect Dis, 2002 Aug 15, 35(4), 420 - 7 Epub 2002 Jul 19.
Association between antimicrobial resistance among pneumococcal isolates and burden of invasive pneumococcal disease in the community; Morita JY et al.; Treatment of infections with drug-resistant strains of Streptococcus pneumoniae (pneumococcus) may fail; whether drug resistance is associated with an increase in the number of serious infections in the community is unknown . We evaluated the relationship between the proportion of antimicrobial-resistant S . pneumoniae isolates and the number of cases of invasive pneumococcal disease . Linear regression models included 1996 county-level data from 38 counties participating in the US Centers for Disease Control and Prevention's Active Bacterial Core Surveillance . Separate models evaluated hospitalized children aged <5 years, nonhospitalized children aged <5 years, adults aged 18-64 years, and adults aged >64 years . The proportion of isolates resistant to > or =3 drug classes was associated with invasive disease in both hospitalized (P=.06) and nonhospitalized (P=.001) children . The proportion of multidrug-resistant pneumococcal isolates did not predict invasive cases among adults . The increasing prevalence of multidrug-resistant pneumococci among children may be leading to an increase in invasive disease.

J Bacteriol, 2002 Aug, 184(16), 4392 - 9
Short-sequence tandem and nontandem DNA repeats and endogenous hydrogen peroxide production contribute to genetic instability of Streptococcus pneumoniae; Pericone CD et al.; Loss-of-function mutations in the following seven pneumococcal genes were detected and analyzed: pspA, spxB, xba, licD2, lytA, nanA, and atpC . Factors associated with these mutations included (i) frameshifts caused by reversible gain and loss of single bases within homopolymeric repeats as short as 6 bases, (ii) deletions caused by recombinational events between nontandem direct repeats as short as 8 bases, and (iii) substitutions of guanine residues caused at an increased frequency by the high levels of hydrogen peroxide (>2 mM) typically generated by this species under aerobic growth conditions . The latter accounted for a frequency as high as 2.8 x 10(-6) for spontaneous mutation to resistance to optochin and was 10- to 200-fold lower in the absence of detectable levels of H2O2 . Some of these mutations appear to have been selected for in vivo during pneumococcal infection, perhaps as a consequence of immune pressure or oxidative stress.

N Engl J Med, 2002 Jul 25, 347(4), 233 - 9
A population-based comparison of strategies to prevent early-onset group B streptococcal disease in neonates; Schrag SJ et al.; BACKGROUND: Guidelines issued in 1996 in the United States recommend either screening of pregnant women for group B streptococcal colonization by means of cultures (screening approach) or assessing clinical risk factors (risk-based approach) to identify candidates for intrapartum antibiotic prophylaxis . METHODS: In a multistate retrospective cohort study, we compared the effectiveness of the screening and risk-based approaches in preventing early-onset group B streptococcal disease (in infants less than seven days old) . We studied a stratified random sample of the 629,912 live births in 1998 and 1999 in eight geographical areas where there was active surveillance for group B streptococcal infection, including all births in which the neonate had early-onset disease . Women with no documented culture for group B streptococcus were considered to have been cared for according to the risk-based approach . RESULTS: We studied 5144 births, including 312 in which the newborn had early-onset group B streptococcal disease . Antenatal screening was documented for 52 percent of the mothers . The risk of early-onset disease was significantly lower among the infants of screened women than among those in the risk-based group (adjusted relative risk, 0.46; 95 percent confidence interval, 0.36 to 0.60) . Because women whose providers had no strategy for prophylaxis may have been misclassified in the risk-based group, we excluded all women with risk factors and adequate time for prophylaxis who did not receive antibiotics . The adjusted relative risk of early-onset disease associated with the screening approach in this secondary analysis was similar--0.48 (95 percent confidence interval, 0.37 to 0.63) . CONCLUSIONS: Routine screening for group B streptococcus during pregnancy prevents more cases of early-onset disease than the risk-based approach . Recommendations that endorse both strategies as equivalent warrant reconsideration .

Int J Med Microbiol, 2002 Jun, 292(1), 27 - 35
Resistance mechanisms of gram-positive bacteria; Berger-Bachi B; The introduction and increasing use of antibiotics for antibacterial therapy has initiated a rapid development and expansion of antibiotic resistance in microorganisms, particularly in human pathogens . Additionally, a shift to an increase in number and severity of Gram-positive infections has been observed the last decades . Common to these pathogens is their tendency to accumulate multiple resistances under antibiotic pressure and selection . Methicillin-resistant Staphylococcus aureus (MRSA), that have acquired multiresistance to all classes of antibiotics, have become a serious nosocomial problem . Recently, the emergence of the first MRSA with reduced vancomycin susceptibility evoked the specter of a totally resistant S . aureus . Problems with multiresistance expand also to penicillin-resistant Streptococcus pneumoniae that are partially or totally resistant to multiple antibiotics, and to vancomycin-resistant Enterococcus ssp., completely resistant to all commonly used antibiotics . The rapid development of resistance is due to mutational events and/or gene transfer and acquisition of resistance determinants, allowing strains to survive antibiotic treatment.

Aust Dent J, 2002 Jun, 47(2), 156 - 62
Oral health of children with gastro-esophageal reflux disease: a controlled study; Linnett V et al.; BACKGROUND: The aim of this study was to compare the dental health of children with gastro-esophageal reflux disease (GERD) with a healthy control group . METHODS: Dental examinations were conducted for 52 children (31 boys and 21 girls) with a definitive history of GERD . For every subject enrolled in the study, a healthy control sibling without the condition was recruited . Medical histories were obtained from medical records, and dental and dietary histories were obtained from parents . The teeth were examined for erosion, dental caries, and enamel hypoplasia, and sampled for Streptococcus mutans . RESULTS: The prevalence of erosion by teeth was found to be statistically significant between GERD patients (14 per cent) and controls (10 per cent) (p<0.05) . GERD patients had erosion in more permanent teeth compared to controls (4 per cent vs 0.8 per cent, p<0.05), and more severe erosion (p<0.05) . Caries experience was also higher in GERD patients compared to controls (p<0.05) . Although there were more subjects with Streptococcus mutans in the GERD group compared to the control group (42 per cent vs 25 per cent), the difference was not statistically significant . CONCLUSIONS: Children with GERD have more erosion and dental caries compared to healthy controls and should be targeted for increased preventive and restorative care.

Indian J Pediatr, 2002 Jun, 69(6), 471 - 5
Clinical score card for diagnosis of group A streptococcal sore throat; Nandi S et al.; OBJECTIVE: Group A beta hemolytic streptococcus (GAS) sore throat primarily occurs among children in 5-15 years age group, and if not treated appropriately causes rheumatic fever/rheumatic heart disease (RF/RHD) . Present study was aimed at validation of a clinical scoring system for diagnosis of GAS . METHODS: Five hundred and thirty six children in 5-15 years age group were enrolled by systematic random selection of households from a peri-urban slum of Chandigarh . They were visited fortnightly at their home for one year to record signs and symptoms of cough and cold . Throat swabs were collected in 918 episodes, of which 123 (13.4%) were GAS culture positive . RESULT: Significant association of GAS was found with pain in the throat, enlarged tonsils, pharyngeal erythema and tender cervical lymphadenopathy . According to the percentage positivity of GAS culture, weighted scores were assigned to age of the child, season of occurrence, fever, size of tonsil, pharyngeal erythema and exudate, lymphadenopathy and pain in throat . Combinations of various symptoms and signs gave sensitivity of 86-89% and specificity of 83-89% whereas clinical score of 15 or more had 91% sensitivity and 98% specificity for diagnosis of GAS pharyngitis . CONCLUSION: As the level of clinical acumen and prevalence of GAS may differ in different primary care settings of the country, the proposed scoring system should be validated and adapted to suit local conditions before establishing it in the primary prophylaxis strategy to prevention of RF/RHD.

Orv Hetil, 2002 Jun 16, 143(24), 1479 - 82
{Experience in the screening of Streptococcus group B infection during pregnancy: can severe neonatal infection be prevented?}; Szabo J et al.; INTRODUCTION, OBJECT: GBS has been responsible for most cases of severe perinatal infection in the last few decades . 10-30% of women is colonised; the vertical transmission is approximately 50% with pregnant carriers . Since the bacterium is responsible for approximately 50% of perinatal sepsis's, and the same time patients may recover with severe residual symptoms, prevention is of great importance . METHOD: The authors screened 1762 out of 2214 women before giving birth at the Obst . and Gyn . Ward of the St . Jones Hosp . and the Obst . and Gyn . Ward of Semmelweis University Kutvolgyi Clinic between May . 1998 and Dec . 1999 following the recommendations issued in 1992 and modified in 1997 by the Committee on Infectious Diseases and the Committee on Fetus and Newborn . RESULTS: The rate of positive cultures was approximately 10%, and the rate of colonised newborn was 1.36% . No severe diseases with residual symptoms were recorded during the period of examination . CONCLUSIONS: On the bases of the international literature and their own experiences the authors recommend the GBS screening and prophylaxis by antibiotics based on positive cultures and risk factors.

Kokubyo Gakkai Zasshi, 2002 Jun, 69(2), 119 - 27
{Cloning and sequence analysis of a sialidase gene (siaHI) from Bacteroides forsythus ATCC 43037}; Hiroaki I; Bacteroides forsythus is known as a periodontopathogen associated with periodontitis, and it produces a tripsin-like protease, cell-death inducing factor, and sialidase (neuraminidase), as putative virulence factors . The purpose of this study was to clone the sialidase gene from B . forsythus ATCC 43037, and to analyze the biological characteristics . A positive clone (pHI-1) was successfully isolated, among a total of 455 recombinant clones, using a filter paper sialidase assay with the fluorogenic sialidase substrate 2'-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid (MUNeuNAc) . Sequencing of the inserted DNA of pHI-1(3.2 kbp) was carried out, and analysis of the sequence with DNASIS software revealed that the ORF (designated siaHI: 1.4 kbp) would code for the protein with a deduced molecular mass of 52 kDa and a pI of 6.60 . Furthermore, we confirmed that siaHI gene was contained in chromosomal DNA from B . forsythus ATCC 43037 and the 3 clinical isolates of B . forsythus . The highest amino acid sequence homology was observed between siaHI gene and a part of sialidase gene from Streptococcus pnumoniae . This is the first report on the cloning and expression of the B . forsythus sialidase gene.

Nucleic Acids Res, 2002 Jul 15, 30(14), 3152 - 62
Identification of 113 conserved essential genes using a high-throughput gene disruption system in Streptococcus pneumoniae; Thanassi JA et al.; The recent availability of bacterial genome sequence information permits the identification of conserved genes that are potential targets for novel antibiotic drug discovery . Using a coupled bioinformatic/experimental approach, a list of candidate conserved genes was generated using a Microbial Concordance bioinformatics tool followed by a targeted disruption campaign . Pneumococcal sequence data allowed for the design of precise PCR primers to clone the desired gene target fragments into the pEVP3 'suicide vector' . An insertion-duplication approach was employed that used the pEVP3 constructs and resulted in the introduction of a selectable chloramphenicol resistance marker into the chromosome . In the case of non-essential genes, cells can survive the disruption and form chloramphenicol-resistant colonies . A total of 347 candidate reading frames were subjected to disruption analysis, with 113 presumed to be essential due to lack of recovery of antibiotic-resistant colonies . In addition to essentiality determination, the same high-throughput methodology was used to overexpress gene products and to examine possible polarity effects for all essential genes.

J Infect Dis, 2002 Jul 15, 186(2), 220 - 6 Epub 2002 Jun 17.
Validation of immunoglobulin G enzyme-linked immunosorbent assay for antibodies to pneumococcal surface adhesin A in the diagnosis of pneumococcal pneumonia among adults in Kenya; Scott JA et al.; Epidemiologic studies of pneumococcal pneumonia, including vaccine efficacy trials, are hampered by a lack of sensitive and specific diagnostic tests . Pneumococcal surface adhesin A (PsaA) is a genetically conserved, surface-expressed protein common to all serotypes of Streptococcus pneumoniae and is highly immunogenic . Detection of anti-PsaA immunoglobulin G by recombinant PsaA enzyme-linked immunosorbent assay was evaluated for diagnosis of pneumococcal pneumonia in paired serum samples from 4 adult populations: 47 healthy control subjects, 56 clinic control subjects without pneumococcal disease syndromes, 109 patients with pneumococcal pneumonia, and 93 pneumonia patients with no evidence of pneumococcal etiology . By considering a 2-fold increase in antibody concentration as positive, sensitivity was 0.70, and specificity was 0.98 . With a 1.3-fold increase, these were 0.89 and 0.98, respectively . The test's performance was not affected by the patients' human immunodeficiency virus status or by the pneumococcal serotype . The combination of high sensitivity and high specificity makes this an ideal assay for epidemiologic studies of pneumococcal pneumonia.

J Infect Dis, 2002 Aug 1, 186(3), 341 - 50 Epub 2002 Jul 10.
Lethal synergism between influenza virus and Streptococcus pneumoniae: characterization of a mouse model and the role of platelet-activating factor receptor; McCullers JA et al.; A lethal synergism exists between influenza virus and pneumococcus, which likely accounts for excess mortality from secondary bacterial pneumonia during influenza epidemics . Characterization of a mouse model of synergy revealed that influenza infection preceding pneumococcal challenge primed for pneumonia and led to 100% mortality . This effect was specific for viral infection preceding bacterial infection, because reversal of the order of administration led to protection from influenza and improved survival . The hypothesis that influenza up-regulates the platelet-activating factor receptor (PAFr) and thereby potentiates pneumococcal adherence and invasion in the lung was examined in the model . Groups of mice receiving CV-6209, a competitive antagonist of PAFr, had survival rates similar to those of control mice, and lung and blood bacterial titers increased during PAFr inhibition . These data suggest that PAFr-independent pathways are operative in the model, prompting further study of receptor interactions during pneumonia and bacteremia . The model of lethal synergism will be a useful tool for exploring this and other mechanisms underlying viral-bacterial interactions.

Med Oral, 2002 Jul-Oct, 7(4), 284 - 92
Quantitative relationship between salivary level of Streptococcus mutans and Candida albicans in children with Down's syndrome; Linossier A et al.; OBJECTIVE: The actual work intends to establish a correlation between quantitative counts for Streptococcus mutans and Candida albicans in the saliva of patients with Down syndrome (DS), and in mentally deficient (MD) patients, with respect to a normal group (C ) . DESIGN OF THE STUDY: This study was performed in 166 children (49 DS, 60MD and 57C), whose saliva samples were grown on TYCSB agar and Sabouraud agar . Subsequently, microbiological analysis, scanning electron microscopy and aggregation assays were made . The results were statistically evaluated using the variance analysis (ANOVA) and the Student "t" test for unpaired data . RESULTS: A correlation of 0.45 was found for group C, 0.55 in DS patients and 0.37 in MD patients, when comparing counts of S . mutans and C . albicans in saliva . Scanning electron microscopy analysis showed coaggregation between S . mutans and C . albicans and this was confirmed by in vitro experiments of S . mutans and C . albicans made on nitrocellulose filters . CONCLUSIONS: This kind of association between bacteria and fungi contributes to justify a pathogenic synergy among several microorganisms, as well as some infectious local or systemic manifestations, depending on the immunity status of the patient.

Front Biosci, 2002 Aug 01, 7, d1798 - 814
Extracellular-peptide control of competence for genetic transformation in Streptococcus pneumoniae; Claverys JP et al.; Bacteria, which often are subjected to fluctuations in nutrients, temperature, radiation, pH, etc., adapt to the physico-chemical environment they live in by making the appropriate changes in their gene expression patterns . During the last decades it has become increasingly clear that bacteria, in addition, have a "social life", and that changes in gene expression can also be elicited by the presence of other bacteria . Traditionally bacteria have been viewed as solitary organisms that in general do not interact with other bacteria in a coordinated manner . Recent advances in the field of bacterial cell-to-cell communication has proved this to be a misconception, and mounting evidence now show that bacterial group behaviour is ubiquitous in nature . Competence for natural genetic transformation in Streptococcus pneumoniae, which has been studied for more than seventy years, has become a paradigm for intercellular communication and cell density dependent regulation of gene expression in Gram-positive bacteria . There has been rapid progress recently in elucidating the molecular mechanisms behind regulation of natural competence in S . pneumoniae . In this review, we describe the current status of our knowledge of natural competence in this bacterium, with particular emphasis on the early phase of competence induction.

Zhonghua Yan Ke Za Zhi, 2002 May, 38(5), 292 - 4
{Distribution and shifting trends of the pathogens for bacterial keratitis}; Sun X et al.; OBJECTIVE: To study the distribution and shifting trends of corneal bacterial isolates from bacterial keratitis retrospectively . METHODS: The data of bacterial cultures of 2 220 corneal isolates from January, 1989 to December, 1998 were reviewed . RESULTS: During this 10-year period, 2 220 consecutive corneal cultures were obtained, and a positive-culture was recovered in 490 isolates, the positive rate being 22.1% . In the 490 positive-cultures, Gram-positive cocci and Gram-negative bacilli represented 51.0% and 39.4% respectively . Gram-positive bacilli was 9.2% . Pseudomonas aeruginosa was isolated the most commonly in the corneal isolates (32.2%), followed by coagulase-negative staphylococcus (18.6%) . Streptococcus pneumoniae represented 12.0% . During this period, we documented a gradual increase in the number of Gram-positive cocci coupled with a decrease of the number of Gram-negative bacilli . CONCLUSION: Pseudomonas aeruginosa and coagulase-negative staphylococcus are the most common pathogens in bacterial keratitis in the north part of China . At present, the increased recovery of Gram-positive cocci and decreased of Gram-negative bacilli from keratitis isolates present an important challenge to the ophthalmology.

J Med Microbiol, 2002 Jul, 51(7), 595 - 600
Typing of human isolates of Streptococcus agalactiae (group B streptococcus, GBS) strains from Zimbabwe; Moyo SR et al.; Serotyping and genotyping are important tools in epidemiological studies of group B streptococcal (GBS) infections, which are important diseases in man, particularly in newborns . In the present study, 241 GBS isolates from Zimbabwe, comprising 124 carrier isolates from pregnant women and 117 isolates from patients hospitalised for various diseases, were serotyped . Antibodies specific for the capsular polysaccharide antigens (CPAs) Ia, Ib and II-V and antibodies specific for the surface-localised proteins, c(alpha), c(beta), R1, R3 and R4 were used for serotyping . Strains of the CPA types Ia (17%), III (47.7%) and V (23.2%) predominated . Of the various protein antigens, c(alpha) and R4 were expressed with highest frequency, c(alpha) by 100% of the CPA type Ia strains and R4 by 92% of the CPA type III strains . The R3 protein occurred frequently (24%), especially in type V strains (84%) . A total of 25 serovariants was detected in the strain collection with the variants Ia/c(alpha) (16%), III/R4 (43.5%) and V/c(alpha), R3 (14.1%) occurring with the highest frequency . Serotype and subtype distribution of the carrier isolates were essentially similar to those of the disease-associated isolates . Genomic heterogeneity was demonstrated by pulsed-field gel electrophoresis of type III/R4 and type V/c(alpha), R3 isolates, but to a much lesser extent than recorded with Norwegian strains . These results demonstrate that many variants of GBS occur in the Zimbabwean population . The data obtained may assist in the formulation of a possible future GBS vaccine for Zimbabwe and perhaps for other African countries.

Minerva Pediatr, 2002 Aug, 54(4), 295 - 303
The pneumococcal conjugate vaccine; Jacobson RM et al.; Streptococcus pneumoniae is the most frequent cause of otitis media, sinusitis, and pneumonia in children . It is also one of the most common causes of invasive bacterial infections in children including bacteremia and meningitis . One of the current issues regarding S . pneumoniae is the emergence of pneumococcal strains resistant to penicillin and other antibiotics . Children less than two years of age suffer an increased incidence of invasive pneumococcal disease but fail to respond to the 23-valent polysaccharide vaccine because of the immaturity of the T-cell independent immune function . Covalently conjugating the polysaccharide antigen to a carrier protein improves the immune response by permitting the host to utilize a T-cell dependent immune response that is adequately mature in children less than two years of age . Immunogenicity studies of the currently licensed heptavalent conjugated polysaccharide vaccine, (Prevnar, marketed by Wyeth Lederle Vaccines) demonstrated that infants vaccinated with three doses 2 months apart at 2, 4, and 6 months of age successfully developed antibodies to all 7 serotypes; booster doses at 12-15 months demonstrated an amnestic response for each serotype . Immunogenicity studies have similarly demonstrated successful responses in children with sickle cell disease and human immunodeficiency virus infection . An efficacy trial involving nearly 38,000 subjects demonstrated the vaccine's effectiveness in healthy children against invasive pneumococcal disease as well as against pneumonia and otitis media . Currently the US Advisory Committee on Immunization Practices (ACIP) recommends that all infants and children under 24 months of age receive the vaccine . The ACIP recommends that infants receive the vaccine routinely at 2, 4 and 6 months with a fourth dose at 12 to 15 months of age . Infants may receive the first dose as early as 6 weeks of age . The vaccine is also indicated for children 24 to 59 months of age who are at high risk for pneumococcal infection . Adverse events include local reactions in the first two days following vaccination such as approximately 10% reporting erythema, 10% induration, and 20% tenderness . Fever of 38 degrees C or higher occurred in 15% to 25% of children in the first two days following vaccination . Follow-up studies should address important questions regarding the use of pneumococcal conjugate vaccine and other age groups.

AIDS, 2002 Jul 5, 16(10), 1409 - 17
Pneumococcal disease in HIV-infected Malawian adults: acute mortality and long-term survival; Gordon SB et al.; OBJECTIVE: HIV-infected patients in Africa are vulnerable to severe recurrent infection with Streptococcus pneumoniae, but no effective preventive strategy has been developed . We set out to determine which factors influence in-hospital mortality and long-term survival of Malawians with invasive pneumococcal disease . DESIGN, SETTING AND PATIENTS: Acute clinical features, inpatient mortality and long-term survival were described among consecutively admitted hospital patients with S . pneumoniae in the blood or cerebrospinal fluid . Factors associated with inpatient mortality were determined, and patients surviving to discharge were followed to determine their long-term outcome . RESULTS: A total of 217 patients with pneumococcal disease were studied over an 18-month period . Among these, 158 out of 167 consenting to testing (95%) were HIV positive . Inpatient mortality was 65% for pneumococcal meningitis (n = 64), 20% for pneumococcaemic pneumonia (n = 92), 26% for patients with pneumococcaemia without localizing signs (n = 43), and 76% in patients with probable meningitis (n = 17) . Lowered consciousness level, hypotension, and age exceeding 55 years at presentation were associated with inpatient death, but not long-term outcome in survivors . Hospital survivors were followed for a median of 414 days; 39% died in the community during the study period . Outpatient death was associated with multilobar chest signs, oral candidiasis, and severe anaemia as an inpatient . CONCLUSION: Most patients with pneumococcal disease in Malawi have HIV co-infection . They have severe disease with a high mortality rate . At discharge, all HIV-infected adults have a poor prognosis but patients with multilobar chest signs or anaemia are at particular risk.

AIDS, 2002 Jul 5, 16(10), 1351 - 6
The microbicide cyanovirin-N expressed on the surface of commensal bacterium Streptococcus gordonii captures HIV-1; Giomarelli B et al.; OBJECTIVE: To explore the feasibility of expressing the potent HIV-inactivating protein, cyanovirin-N (CV-N), in the human commensal bacterium Streptococcus gordonii, as a possible approach for local delivery of CV-N to prevent sexual transmission of HIV-1 . DESIGN AND METHODS: To express CV-N in S . gordonii, we used the host-vector system we had previously developed . CV-N was expressed as a fusion protein both attached to the bacterial surface and secreted in soluble form in the supernatant of liquid cultures . The soluble form of recombinant CV-N was tested for gp120-binding activity in an enzyme-linked immunosorbent assay, whereas S . gordonii strain expressing CV-N on the surface was analyzed in an in vitro HIV capturing assay . RESULTS: Two recombinant S . gordonii strains secreting or displaying CV-N on the bacterial surface were constructed and the expression of CV-N was confirmed by immunoblot and flow-cytometric analysis . The secreted form of recombinant CV-N exhibited a concentration-dependent binding to the envelope glycoprotein gp120 of HIV-1, whereas CV-N displayed on the bacterial surface was able to capture HIV virions efficiently . CONCLUSION: The anti-HIV protein CV-N in S . gordonii was expressed in a biologically active form . This represents a first step in the development of a system to deliver and maintain an effective concentration of a microbicide in the vaginal mucosa.

J Biol Chem, 2002 Sep 27, 277(39), 36678 - 88 Epub 2002 Jul 18.
Structure and flexibility of Streptococcus agalactiae hyaluronate lyase complex with its substrate . Insights into the mechanism of processive degradation of hyaluronan; Mello LV et al.; Streptococcus agalactiae hyaluronate lyase degrades primarily hyaluronan, the main polysaccharide component of the host connective tissues, into unsaturated disaccharide units as the end product . Such function of the enzyme destroys the normal connective tissue structure of the host and exposes the tissue cells to various bacterial toxins . The crystal structure of hexasaccharide hyaluronan complex with the S . agalactiae hyaluronate lyase was determined at 2.2 A resolution; the mechanism of the catalytic process, including the identification of specific residues involved in the degradation of hyaluronan, was clearly identified . The enzyme is composed structurally and functionally from two distinct domains, an alpha-helical alpha-domain and a beta-sheet beta-domain . The flexibility of the protein was investigated by comparing the crystal structures of the S . agalactiae and the Streptococcus pneumoniae enzymes, and by using essential dynamics analyses of CONCOORD computer simulations . These revealed important modes of flexibility, which could be related to the protein function . First, a rotation/twist of the alpha-domain relative to the beta-domain is potentially related to the mechanism of processivity of the enzyme; this twist motion likely facilitates shifting of the ligand along the catalytic site cleft in order to reposition it to be ready for further cleavage . Second, a movement of the alpha- and beta-domains with respect to each other was found to contribute to a change in electrostatic characteristics of the enzyme and appears to facilitate binding of the negatively charged hyaluronan ligand . Third, an opening/closing of the substrate binding cleft brings a catalytic histidine closer to the cleavable substrate beta1,4-glycosidic bond . This opening/closing mode also reflects the main conformational difference between the crystal structures of the S . agalactiae and the S . pneumoniae hyaluronate lyases.

Am Fam Physician, 2002 Jul 1, 66(1), 119 - 24
Common bacterial skin infections; Stulberg DL et al.; Family physicians frequently treat bacterial skin infections in the office and in the hospital . Common skin infections include cellulitis, erysipelas, impetigo, folliculitis, and furuncles and carbuncles . Cellulitis is an infection of the dermis and subcutaneous tissue that has poorly demarcated borders and is usually caused by Streptococcus or Staphylococcus species . Erysipelas is a superficial form of cellulitis with sharply demarcated borders and is caused almost exclusively by Streptococcus . Impetigo is also caused by Streptococcus or Staphylococcus and can lead to lifting of the stratum corneum resulting in the commonly seen bullous effect . Folliculitis is an inflammation of the hair follicles . When the infection is bacterial rather than mechanical in nature, it is most commonly caused by Staphylococcus . If the infection of the follicle is deeper and involves more follicles, it moves into the furuncle and carbuncle stages and usually requires incision and drainage . All of these infections are typically diagnosed by clinical presentation and treated empirically . If antibiotics are required, one that is active against gram-positive organisms such as penicillinase-resistant penicillins, cephalosporins, macrolides, or fluoroquinolones should be chosen . Children, patients who have diabetes, or patients who have immunodeficiencies are more susceptible to gram-negative infections and may require treatment with a second- or third-generation cephalosporin.

Acta Otolaryngol, 2002 Jun, 122(4), 413 - 9
Effect of neuraminidase on receptor-mediated adherence of Streptococcus pneumoniae to chinchilla tracheal epithelium; Tong HH et al.; The trachea whole organ perfusion technique was used to study the effect of the disruption of the Streptococcus pneumoniae neuraminidase nanA gene on bacterial adherence and alteration of the carbohydrate surface structures of respiratory epithelial cells . Six different lectin probes were used to examine alterations of the cell surface carbohydrates in chinchilla tracheal epithelium incubated in vitro with S . pneumoniae deltaNA1, a neuraminidase-deficient mutant, or its D39 parent strain . The labeling pattern revealed that the binding of wheat germ agglutinin (WGA), Erythrina cristagalli lectin (ECL), peanut agglutinin (PNA), Bandeiraea simplicifolia lectin II (BSL II) and succinylated WGA was significantly increased in the luminal surface of the trachea in the D39-incubated cohort compared with the uninfected control, which indicated that GlcNAc and D-galactose residues were exposed . Concurrently, decreased labeling with Sambucus nigra agglutinin (SNA) indicated that there were few sialic acid residues remaining in the tracheal epithelium subsequent to incubation with D39 . The deltaNA1 neuraminidase-deficient mutant, however, did not induce any significant changes in the lectin labeling patterns, which were comparable to those of the control cohort . Moreover, adherence data expressed as colony-forming units (CFU) of S . pneumoniae per millimeter of trachea indicated a significant decline in the ability of deltaNA1 to adhere in vitro . We propose that products of the nanA gene have a significant impact on changes in the carbohydrate moieties in the tracheal epithelium, and may be responsible for the previously reported increased ability of the D39 parent to colonize the nasopharynx and invade the middle ear.

J Mol Microbiol Biotechnol, 2002 Jul, 4(4), 347 - 55
The bacteriocins of ruminal bacteria and their potential as an alternative to antibiotics; Russell JB et al.; Beef cattle have been fed ionophores and other antibiotics for more than 20 years to decrease ruminal fermentation losses (e.g methane and ammonia) and increase feed efficiency, and these improvements have been explained by an inhibition of gram-positive ruminal bacteria . Ionophores are not used to treat human disease, but there has been an increased perception that antibiotics should not be used as feed additives . Some bacteria produce small peptides (bacteriocins) that inhibit gram-positive bacteria . In vitro experiments indicated that the bacteriocin, nisin, and the ionophore, monensin, had similar effects on ruminal fermentation . However, preliminary results indicated that mixed ruminal bacteria degraded nisin, and the ruminal bacterium, Streptococcus bovis, became highly nisin-resistant . A variety of ruminal bacteria produce bacteriocins, and bacteriocin production has, in some cases, been correlated with changes in ruminal ecology . Some ruminal bacteriocins are as potent as nisin in vitro, and resistance can be circumvented . Based on these results, ruminal bacteriocins may provide an alternative to antibiotics in cattle rations.

Can Vet J, 2002 Jul, 43(7), 523 - 7
Bacterial contamination of colostrum fed to newborn calves in Québec dairy herds; Fecteau G et al.; A convenience sample of 234 colostral specimens, collected directly from the nursing bottle immediately prior to the first feeding, was studied . Samples originated from 6 farms and were collected over 24 months . Routine bacteriologic techniques were used to quantify the bacterial load of the colostrum, as well as to identify the bacteria . Overall, at least 1 microorganism was cultured from 221 colostral samples (94.4%) . By using the upper tolerance level of 100,000 bacteria/mL, 84 samples (35.9%) were considered contaminated . Staphylococcus spp . (57.7%), gram-negative rods (47.9%), coliforms (44.0%), and Streptococcus uberis (20.5%) were among the most frequently isolated bacteria . The relative risk (RR) of contamination with more than 100,000 bacteria/mL was significantly greater in warm months {RR = 2.55, 95% confidence interval (CI): 1.63 to 4.02} than in cool months and in colostrum offered to male calves (RR = 1.55, 95% CI: 1.09 to 2.20) . Bacterial load was also associated with the farm of origin (P < 0.0001) . When assessing colostrum management, one should consider bacterial contamination . Multiple factors are likely associated with the degree of contamination, and farm-specific factors may be important . Further studies are necessary to evaluate the impact of bacterial contamination of colostrum on neonatal health.

FEBS Lett, 2002 Jul 17, 523(1-3), 119 - 22
3-Chloro-DL-alanine resistance by L-methionine-alpha-deamino-gamma-mercaptomethane-lyase activity; Yoshimura M et al.; The antibacterial agent 3-chloro-DL-alanine (3CA) is an inhibitor of peptidoglycan synthesis . Fusobacterium nucleatum and Porphyromonas gingivalis, the bacteria responsible for oral malodor, are shown to be resistant to 1 mM 3CA, whereas Streptococcus mutans and Escherichia coli are sensitive to this antibacterial agent at the same concentration . We isolated the 3CA resistance gene from F . nucleatum and showed that the gene encodes an L-methionine-alpha-deamino-gamma-mercaptomethane-lyase that catalyzes the alpha,gamma-elimination of L-methionine to produce methyl mercaptan . The enzyme also exhibits 3CA chloride-lyase (deaminating) activity . This antibacterial agent is expected to be useful for specific selection of malodorous oral bacteria producing high amounts of methyl mercaptan.

Mol Microbiol, 2002 Jul, 45(2), 411 - 21
Uptake of transforming DNA in Gram-positive bacteria: a view from Streptococcus pneumoniae; Berge M et al.; In a working model for the uptake of transforming DNA based on evidence taken from both Bacillus subtilis and Streptococcus pneumoniae, the ComG proteins are proposed to form a structure that provides access for DNA to the ComEA receptor through the peptidoglycan . DNA would then be delivered to the ComEC-ComFA transport complex . A DNA strand would be degraded by a nuclease, while its complement is pulled into the cell by ComFA through an aqueous pore formed by ComEC . The nuclease is known in S . pneumoniae only as EndA . We have examined the processing (i.e . binding, degradation and internalization) of DNA in S . pneumoniae strains lacking candidate uptake proteins . Mutants were generated by transposon insertion in endA, comEA/C, comFA/C, comGA and dprA . Processing of DNA was abolished only in a comGA mutant . As significant binding was measured in comEA mutants, we suggest the existence of two stages in binding: surface attachment (abolished in a comGA mutant) required for and preceding deep binding (by ComEA) . Abolition of degradation in comGA and comEA mutants indicated that, despite its membrane location, EndA cannot access donor DNA by itself . We propose that ComEA is required to deliver DNA to EndA . DNA was still bound and degraded in comEC and comFA mutants . We conclude that recruitment of EndA can occur in the absence of ComEC or ComFA and that EndA is active even when the single strands it produces are not pulled into the cell . Finally, inactivation of dprA had no effect on the internalization of DNA, indicating that DprA is required at a later stage in transformation.

Proc Natl Acad Sci U S A, 2002 Jul 23, 99(15), 10078 - 83 Epub 2002 Jul 16.
Genome sequence of a serotype M3 strain of group A Streptococcus: phage-encoded toxins, the high-virulence phenotype, and clone emergence; Beres SB et al.; Genome sequences are available for many bacterial strains, but there has been little progress in using these data to understand the molecular basis of pathogen emergence and differences in strain virulence . Serotype M3 strains of group A Streptococcus (GAS) are a common cause of severe invasive infections with unusually high rates of morbidity and mortality . To gain insight into the molecular basis of this high-virulence phenotype, we sequenced the genome of strain MGAS315, an organism isolated from a patient with streptococcal toxic shock syndrome . The genome is composed of 1,900,521 bp, and it shares approximately 1.7 Mb of related genetic material with genomes of serotype M1 and M18 strains . Phage-like elements account for the great majority of variation in gene content relative to the sequenced M1 and M18 strains . Recombination produces chimeric phages and strains with previously uncharacterized arrays of virulence factor genes . Strain MGAS315 has phage genes that encode proteins likely to contribute to pathogenesis, such as streptococcal pyrogenic exotoxin A (SpeA) and SpeK, streptococcal superantigen (SSA), and a previously uncharacterized phospholipase A(2) (designated Sla) . Infected humans had anti-SpeK, -SSA, and -Sla antibodies, indicating that these GAS proteins are made in vivo . SpeK and SSA were pyrogenic and toxic for rabbits . Serotype M3 strains with the phage-encoded speK and sla genes increased dramatically in frequency late in the 20th century, commensurate with the rise in invasive disease caused by M3 organisms . Taken together, the results show that phage-mediated recombination has played a critical role in the emergence of a new, unusually virulent clone of serotype M3 GAS.

Antimicrob Agents Chemother, 2002 Aug, 46(8), 2712 - 5
Topoisomerase mutations associated with in vitro selection of resistance to moxifloxacin in Streptococcus pneumoniae; Houssaye S et al.; We analyzed the frequencies of selection, the order of acquisition, and the mutations selected on moxifloxacin in two wild-type pneumococcal strains, R6 and 5714 . The first selection step showed either a single GyrA mutation or no mutation in any of the quinolone resistance-determining regions . Second-step mutants selected had either a second mutation in ParC or in ParE . Moxifloxacin could belong to these fluoroquinolones, which preferentially target GyrA though probably acting equally through both gyrase and topoisomerase IV.

Antimicrob Agents Chemother, 2002 Aug, 46(8), 2671 - 5
Incidence, epidemiology, and characteristics of quinolone-nonsusceptible Streptococcus pneumoniae in Croatia; Pankuch GA et al.; Among 585 Streptococcus pneumoniae strains isolated in 22 Croatian hospitals 21 strains (3.6%) were quinolone nonsusceptible . MICs of all quinolones were high for seven strains tested with the same serotype (23F) and mutations in gyrA, parC, and parE . The remaining 14 strains were more heterogeneous and had mutations only in parC and/or parE, and the MICs of quinolones were lower for these strains.

Antimicrob Agents Chemother, 2002 Aug, 46(8), 2665 - 7
Activities of six different quinolones against clinical respiratory isolates of Streptococcus pneumoniae with reduced susceptibility to ciprofloxacin in Spain; Perez-Trallero E et al.; Six quinolones were tested on 817 consecutive pneumococcal isolates for which ciprofloxacin MICs were high (> or =2 microg/ml); the isolates had been collected during two recent Spanish surveillance studies . For strains for which the ciprofloxacin MIC was >or =4 microg/ml, the MICs at which 90% of the isolates tested against gemifloxacin, moxifloxacin, gatifloxacin, sparfloxacin, levofloxacin, and ofloxacin were inhibited were 0.25, 1, 1, 1, 4 and 16 microg/ml, respectively, and the corresponding prevalences of resistance were 0, 1, 4.5, 9.5, 8.4 and 23% . The proportion of isolates for which the ciprofloxacin MIC is high has increased over time.

Antimicrob Agents Chemother, 2002 Aug, 46(8), 2507 - 12
PCR-based ordered genomic libraries: a new approach to drug target identification for Streptococcus pneumoniae; Belanger AE et al.; Described here are the development and validation of a novel approach to identify genes encoding drug targets in Streptococcus pneumoniae . The method relies on the use of an ordered genomic library composed of PCR amplicons that were generated under error-prone conditions so as to introduce random mutations into the DNA . Since some of the mutations occur in drug target-encoding genes and subsequently affect the binding of the drug to its respective cellular target, amplicons containing drug targets can be identified as those producing drug-resistant colonies when transformed into S . pneumoniae . Examination of the genetic content of the amplicon giving resistance coupled with bioinformatics and additional genetic approaches could be used to rapidly identify candidate drug target genes . The utility of this approach was verified by using a number of known antibiotics . For drugs with single protein targets, amplicons were identified that rendered S . pneumoniae drug resistant . Assessment of amplicon composition revealed that each of the relevant amplicons contained the gene encoding the known target for the particular drug tested . Fusidic acid-resistant mutants that resulted from the transformation of S . pneumoniae with amplicons containing fusA were further characterized by sequence analysis . A single mutation was found to occur in a region of the S . pneumoniae elongation factor G protein that is analogous to that already implicated in other bacteria as being associated with fusidic acid resistance . Thus, in addition to facilitating the identification of genes encoding drug targets, this method could provide strains that aid future mechanistic studies.

Antimicrob Agents Chemother, 2002 Aug, 46(8), 2349 - 57
Analysis of penicillin-binding protein genes of clinical isolates of Streptococcus pneumoniae with reduced susceptibility to amoxicillin; du Plessis M et al.; The recent emergence of pneumococcal isolates exhibiting an unusual resistance phenotype of higher amoxicillin MICs in relation to the penicillin MICs prompted an analysis of the pbp genes from three such strains isolated in France . For comparison, three amoxicillin-susceptible strains were included in the study . DNA sequence analysis of the pbp2x, pbp2b, and pbp1a genes revealed extensive sequence divergence in all six isolates compared to the sequences of the genes of penicillin-susceptible strain R6 . With the exception of pbp2b, no amino acid mutations were unique to the resistant isolates . Transformation experiments with cloned pbp genes isolated from one of the resistant isolates demonstrated a stepwise development of amoxicillin resistance involving penicillin-binding proteins (PBPs) 2X, 2B, and 1A . Full resistance, equivalent to that of the donor strain, was achieved only when genomic DNA was transformed into R6(2x/2b/1a) mutants, suggesting that full resistance development in this isolate is mediated by a non-PBP determinant . Moreover, the recently identified murMN resistance determinant does not appear to have any impact on resistance in this isolate . This determinant (from the French isolate) was, however, able to transform an R6 mutant harboring pbp2x, pbp2b, and pbp1a genes from a Hungarian clone with an extremely high level of penicillin resistance so that it had increased levels of penicillin resistance . These results indicate that the development of high-level beta-lactam resistance is a complex process and that the involvement of MurMN in penicillin resistance appears to be dependent on specific mutations in PBPs 2X, 2B, and/or 1A . Furthermore, an additional (as yet unidentified) non-PBP-mediated resistance determinant is required for full resistance development in some pneumococci.

Oral Microbiol Immunol, 2002 Aug, 17(4), 263 - 6
gbpC and pac gene mutations detected in Streptococcus mutans strain GS-5; Sato Y et al.; The Streptococcus mutans gbpC gene encoding cell wall-anchoring glucan-binding protein C is involved in the dextran(alpha-1,6 glucan)-dependent aggregation (ddag) of this organism . Unlike cells of other strains of S . mutans, strain GS-5 cells did not exhibit dextran(alpha-1,6 glucan)-dependent aggregation under any conditions . We therefore hypothesized that the gbpC gene may be mutated in strain GS-5 . Sequencing analysis of the 1752-nucleotide GS-5 gbpC gene revealed a point mutation that switched codon 65 to a TAA termination codon . Strain GS-5 was previously reported also to have a mutation in the pac gene encoding the cell wall-anchored major protein antigen . The laboratory-maintained strain GS-5 is regarded as having lower cariogenicity than the original isolate . The decreased cariogenicity developed during the laboratory culture of strain GS-5 may have been caused by mutations in an environment lacking appropriate selective pressures.

Oral Microbiol Immunol, 2002 Aug, 17(4), 252 - 6
Streptococcus mutans binding to solid phase dextran mediated by the glucan-binding protein C; Sato Y et al.; Streptococcus mutans GbpC is a wall-anchored surface protein which is involved in dextran-dependent aggregation . The GbpC phenotype is observed only in cells grown under stress conditions . In order to detect the GbpC protein of S . mutans, we isolated the wall fraction following digestion of the cell wall of this organism by N-acetylmuramidase, and detected the GbpC protein from S . mutans cells by western analysis with anti-GbpC serum . Interestingly, S . mutans cells exhibiting the negative dextran(alpha-1,6 glucan)-dependent aggregation (ddag) phenotype expressed the protein and could bind to immobilized dextran.

Oral Microbiol Immunol, 2002 Aug, 17(4), 239 - 44
Intracellular and extracellular pHs of Streptococcus mutans after addition of acids: loading and efflux of a fluorescent pH indicator in streptococcal cells; Iwami Y et al.; A pH-sensitive fluorescent dye, 2', 7'-bis-(2-carboxyethyl)-5 and 6-carboxyfluorescein (BCECF), was used to determine intracellular pH (pH(in)) . The efflux of BCECF loaded into oral streptococcal cells was determined after incubation of the cells at 35 degrees C for 20 min in the presence and absence of glucose . In the absence of glucose, the fluorescence of intracellular BCECF in Streptococcus mutans, Streptococcus sanguis, Streptococcus salivarius and Streptococcus sobrinus decreased only very slightly, indicating that the dye could be useful for pH(in) determination . In the presence of glucose, however, the fluorescence decreased by 57% . Thus, the pH(in) of S . mutans cells was measured by the BCECF method in the absence of glucose at various acidic pH levels by adding lactic, acetic and hydrochloric acids to the cell suspensions . The pH(in) was almost equal to the extracellular pH (pH(out)) for pH(out) values of between 8 and 5, indicating that protons permeated easily across the S . mutans cell membrane . For pH(out) between 5 and 4, pH(in) was constant at around 5, suggesting that the cell membrane was impermeable to protons, or that a cytoplasmic buffering system functioned . pH(in) decreased at pH(out) values of < 4 . The constant pH(in) at acidic pH(out) levels could protect intracellular components, such as proteins, against acidification by sugar fermentation.

Oral Microbiol Immunol, 2002 Aug, 17(4), 209 - 14
Identification of the peptide motifs that interact with HLA-DR8 (DRB1*0802) in Streptococcus mutans proteins; Nomura Y et al.; A glucosyltransferase (GTF) and a surface protein antigen (PAc) of Streptococcus mutans have been suggested as possible components of an effective dental caries vaccine . To identify antigenic peptides in GTF and PAc that bind to MHC class II (HLA-DR8, DRB1*0802) molecules, we investigated binding activities to DR8 molecules of overlapping synthetic peptides at several sites in GTF and in the alanine-rich repeating region of PAc using an ELISA-inhibition competitive binding assay for the interaction between the HLA-DR molecule and the PAc (316-334) peptide . Six GTF peptides and 10 PAc peptides strongly bound to the HLA-DR8 molecule . In a homology analysis of the amino acid sequences of the six GTF peptides, two binding motifs were found in L/Y--Y/L-A/N and Y/L--N/G/E--Y-V/L/P . Moreover, a new binding motif in PAc was found in L--Y-A . It is suggested that these binding motifs could be useful in designing a dental caries vaccine in humans.

Scand J Immunol, 2002 Aug, 56(2), 111 - 29
Current state of pneumococcal vaccines; Wuorimaa T et al.; Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis, and acute otitis media in children and adults worldwide . According to World Health Organization estimates, at least 1 million children under 5 years of age die each year from pneumococcal pneumonia . The emergence of resistant strains necessitates the development of an effective vaccine with a large serotype coverage . The 11 most common serotypes cause 72-83% of all serious pneumococcal diseases worldwide . Currently marketed 23-valent pneumococcal polysaccharide vaccine provides large serotype coverage and offers a less expensive option . However, it is efficacious only in adults but not in infants . Conjugate vaccines offer a solution by generating immunological memory already at early age . A recently licensed 7-valent conjugate vaccine is immunogenic and efficacious in infants . Its serotype coverage might be sufficient in Europe and North America, but not in Africa, Asia and Oceania . A need exists to develop pneumococcal vaccines with lower cost and larger serotype coverage . Several 11-valent pneumococcal conjugate vaccines are being evaluated in phase I-III trials . This study reviews the current state of pneumococcal problem and pneumococcal vaccines in clinical use.

Australas J Dermatol, 2002 Aug, 43(3), 194 - 8
Fatal group A streptococcal necrotizing fasciitis and toxic shock syndrome in a patient with psoriasis and chronic renal impairment; Chong AH et al.; A 78-year-old woman presented with rapid onset of skin pain which evolved into oedema, discoloration and infarction . She was diagnosed with group A beta-haemolytic streptococcus (Streptococcus pyogenes) necrotizing fasciitis and streptococcal toxic shock syndrome . The patient had a past history of psoriasis and end-stage renal impairment . Despite treatment with multiple antibiotics in an intensive care unit, the skin infarction involving the upper trunk continued to expand and the patient died within 24 hours of hospital admission . Group A streptococcus and Staphylococcus aureus were cultured from a tissue biopsy . Renal failure and compromised skin barrier function are known to predispose to invasive streptococcal infections, but necrotizing fasciitis has only rarely been reported in association with psoriasis . This case illustrates the fulminant nature of the infection.

J Vet Med B Infect Dis Vet Public Health, 2002 Jun, 49(5), 257 - 9
Molecular characterization of phenotypically CAMP-negative Streptococcus agalactiae isolated from bovine mastitis; Hassan AA et al.; In the present study three phenotypically CAMP-negative Streptococcus agalactiae, isolated from three cows with mastitis, were characterized by molecular analysis . An identification of the S . agalactiae was performed by conventional methods and by PCR amplification of species specific parts of the 16S rRNA gene and the 16S-23S rDNA intergenic spacer region . In addition all three phenotypically CAMP-negative isolates harboured a normal sized CAMP-factor encoding cfb gene indicating a reduced expression of CAMP-factor or a gene defect elsewhere along the pathway of expression . The clonal identity of the three isolates could be demonstrated by macrorestriction analysis of their chromosomal DNA.

J Vet Med B Infect Dis Vet Public Health, 2002 Jun, 49(5), 240 - 4
Plasma haptoglobin concentration in swine after challenge with Streptococcus suis; Knura-Deszczk S et al.; Eight 15-week-old pigs, reared under specific pathogen-free conditions, were inoculated with Streptococcus suis serotype 2 . The animals were monitored before and after challenge by measuring rectal temperature, recording specific clinical symptoms and collecting blood samples for haptoglobin determination . Twenty-four hours after infection, the average haptoglobin plasma concentration of the animal group increased significantly and reached a maximum 4 days post-inoculation, followed by a constant mean level until the end of the trial on day 10 . In spite of individual differences between the animals, an increase in haptoglobin concentration of at least 2.5 times above normal was observed in all infected pigs 1 day after challenge . Twenty-four hours after challenge, lameness was observed in five animals and an elevated body temperature was observed in seven of the eight experimental infected animals . These are the classical clinical symptoms of streptococcal infection . Haptoglobin was shown to increase in acute S . suis infection in pigs.

J Vet Med B Infect Dis Vet Public Health, 2002 Jun, 49(5), 211 - 5
Bacterial colonization and invasion in pigs experimentally exposed to Streptococcus suis serotype 2 in aerosol; Madsen LW et al.; A recently developed porcine model for aerogenous infection with Streptococcus suis serotype 2 was applied in a study of the phases of bacterial colonization and initial invasion . Eighteen pigs were exposed to aerosolized S . suis serotype 2 after pre-exposure to mild acetic acid in aerosol . The animals were killed consecutively within the first six days after challenge . After death, all animals were necropsied and examined by bacteriology, histopathology, and immunohistochemistry . Systemic infection was established in four out of 18 animals exposed to S . suis serotype 2 . All systemically infected animals developed clinical signs and lesions typical of the infection . In four additional animals, subclinical infection was demonstrated by re-isolation of S . suis from the palatine tonsil . However, in all 18 challenged animals, immunohistochemistry demonstrated S . suis serotype 2 antigen in the palatine and/or nasopharyngeal tonsils . In all four systemically infected animals, S . suis serotype 2 antigen was also found in the mandibular lymph node . These observations point towards the tonsils as possible portals of entry for S . suis serotype 2 with subsequent lymphogenous spread . Thus, the present findings parallel the proposed pathogenesis for S . suis serotype 1 infection in pigs.

Ir J Med Sci, 2001 Jul-Sep, 170(3), 198 - 9
Quinolone-associated tendonitis: a potential problem in COPD?
Butler MW, Griffin JF, Quinlan WR, McDonnell TJ.
BACKGROUND: Quinolones have traditionally had limited application in the area of community-acquired respiratory tract infections due to poor cover against Streptococcus pneumoniae . This trend is changing with the broader spectrum of newer fluoroquinolones . A rare serious side effect of fluoroquinolones is tendinopathy . AIMS: This study describes two cases of levofloxacin-associated tendinopathy in patients with severe chronic obstructive pulmonary disease (COPD) and the implications and mechanisms involved are discussed . CONCLUSIONS: The finding of two cases of levofloxacin-induced tendinopathy in our patients suggests that the problem may be more frequent than previously considered . Patients with COPD treated with fluoroquinolones may have other risk factors for tendinopathy such as advanced age, corticosteroid use and renal impairment and merit vigilance for signs of tendonitis.

J Chemother, 2002 Jun, 14(3), 279 - 84
Recent clinical evidence of the efficacy and safety of thiamphenicol glycinate acetylcysteinate and thiamphenicol glycinate; Grassi C et al.; Thiamphenicol is a broad-spectrum antimicrobial agent active against penicillin-resistant Streptococcus pneumoniae, Staphylococcus aureus VISA strains, most methicillin-resistant isolates and atypical pathogens such as Mycoplasma pneumoniae and Chlamydia pneumoniae) . Thiamphenicol is present as glycinate hydrochloride (TG) and glycinate acetylcysteinate (TGA) esters in the parenteral and aerosol dosage form . This multicenter, double-blind, randomized clinical trial aimed to evaluate the efficacy and tolerability of aerosol administration of TGA, compared to TG, in the treatment of acute and/or exacerbated infections of the respiratory tract . Results showed that both treatments ameliorated the symptoms (frequency and severity of cough, difficulty in expectoration) associated with the evaluated pathologies, i.e . tracheobronchitis, acute and exacerbated chronic bronchitis . The investigators rated both treatments Good or Very Good in 90% of patients at the end of treatment, with "Very Good" for patients treated with TGA (37%) compared to 28% of patients treated with TG . Both treatments were well tolerated with fewer than 5% of patients experiencing an adverse event.

Eur J Oral Sci, 2002 Jun, 110(3), 225 - 9
Influence of secondary colonizers and human plasma on the adherence of Porphyromonas gingivalis in vitro; Sato M et al.; The influence of secondary colonizers (Fusobacterium nucleatum and Actinomyces naeslundii) and the effect of human plasma on the adherence of Porphyromonas gingivalis were investigated . Hydroxyapatite (HAP) discs coated with Streptococcus sanguis were immersed in a 3H-labeled bacterial cell suspension of F . nucleatum or A . naeslundii and then in a 14C-labeled P . gingivalis cell suspension . Bacterial cells on the discs were pyrolysed to quantify the radioisotopes released . The cell numbers of secondary colonizers on the discs increased with immersion time and this, in turn, resulted in significantly elevated adherence of P . gingivalis . These two secondary colonizers had very similar positive effects on the adherence of P . gingivalis . Human plasma significantly inhibited the adherence of P . gingivalis and secondary colonizers to S . sanguis-coated HAP discs . Adherence of P . gingivalis and A . naeslundii was strongly inhibited by plasma, while that of F . nucleatum was affected the least . Treatment with plasma, after immersion of streptococcal-coated discs in individual cell suspension of secondary colonizers, also reduced subsequent adherence of P . gingivalis . The rate of decrease was much smaller in F . nucleatum . These results indicate that both F . nucleatum and A . naeslundii enhance the adherence of P . gingivalis, and that the former may play a more important role in the establishment of P . gingivalis in dental plaque where plasma-derived components are present.

Isr Med Assoc J, 2002 Jul, 4(7), 520 - 3
Defense against biologic warfare with superantigen toxins; Kaempfer R et al.; BACKGROUND: Superantigens produced by Staphylococcus aureus and Streptococcus pyogenes are among the most lethal of toxins . Toxins in this family trigger an excessive cellular immune response leading to toxic shock . OBJECTIVES: To design an antagonist that is effective in vivo against a broad spectrum of superantigen toxins . METHODS: Short peptide antagonists were selected for their ability to inhibit superantigen-induced expression of human genes for cytokines that mediate shock . The ability of these peptides to protect mice against lethal toxin challenge was examined . RESULTS: Antagonist peptide protected mice against lethal challenge with staphylococcal enterotoxin B and toxic shock syndrome toxin-1, superantigens that share only 6% overall amino acid homology . Moreover, it rescued mice undergoing toxic shock . Antagonist peptides show homology to a beta-strand/hinge/alpha-helix domain that is structurally conserved among superantigens, yet remote from known binding sites for the major histocompatibility class II molecule and T cell receptor that function in toxic T cell hyperactivation . CONCLUSIONS: The lethal effect of superantigens can be blocked with a peptide antagonist that inhibits their action at the top of the toxicity cascade before activation of T cells occurs . Superantigenic toxin antagonists may serve not only as countermeasures to biologic warfare but may be useful in the treatment of staphylococcal and streptococcal toxic shock, as well as in some cases of septic shock.

J Pediatr, 1974 Jan, 84(1), 21 - 8
Comparison of the antibody response to streptococcal cellular and extracellular antigens in acute pharyngitis; Kaplan EL et al.; The antibody response to the group A carbohydrate moiety of the streptococcal cell wall is of special interest because of its postulated role in the pathogenesis of rheumatic valvulitis . The immune response to this somatic antigen was measured in 159 children with culture-proved group A streptococcal pharyngitis and was compared with that to two extracellular antigens of the Group A streptococcus: streptolysin O and streptococcal DNase B . The data suggest that the maximum anti-A-carbohydrate rise occurs soon after the onset of streptococcal pharyngitis in a fashion similar to the response to some streptococcal extracellular antigens . However, the anti-A-carbohydrate antibody response appeared to be a less sensitive indicator of streptococcal upper respiratory tract infection.

ASDC J Dent Child, 2002 Jan-Apr, 69(1), 81 - 6, 13
Effect of xylitol chewing gum on salivary Streptococcus mutans in preschool children; Autio JT; Dental caries remains a significant problem for poor children in the United States . One strategy for treating dental caries is to suppress streptococcus mutans, the chief pathogen responsible for the disease . The purpose of this study was to evaluate the effect of xylitol gum in salivary S . mutans levels in preschool children . Sixty-one children were randomly assigned into the xylitol group and the control group . The xylitol group chewed gum sweetened only with xylitol (XyliFresh100%, Hershey Food Corporation, U.S.A.) three times a day for three weeks . S . mutans counts were tested using the Dentocult-SM Strip Mutans-test (Orion Diagnostica, Finland) at baseline and after three weeks . The shift from higher S . mutans scores to lower was greater in the xylitol group than in the control group (p;lt0.05) . This study supports the suggestion that chewing xylitol gum may reduce salivary S . mutans levels . Xylitol chewing gum may provide a feasible caries prevention method for preschool children.

Microb Drug Resist, 2002 Summer, 8(2), 79 - 84
Evolutionary barriers to quinolone resistance in Streptococcus pneumoniae; Gillespie SH et al.; It is assumed that bacteria always pay a significant physiological price for the acquisition of resistance to antibiotics . To test whether this was the case for a strain of Streptococcus pneumoniae that develops resistance to fluoroquinolone antibiotics, we selected resistance to these agents in a wild-type strain and measured their fitness in comparative growth experiments . The relative growth rate of a mutant strain selected on ciprofloxacin (parC Serine 79 to Tyrosine) was compared with its susceptible isogenic parent and no significant deficit was found (relative fitness 1.15 95% C.I . +/- 0.2.) . A double mutant, however, had a relative fitness of 0.81 (parC Serine 79 to Tyrosine gyrA Serine 81 to Tyrosine) . Mutant strains selected on gemifloxacin had only a modest increase in minimum inhibitory concentration; thus, second-round mutants were competed with a first-round gyrA Serine 81 to Tyrosine or the susceptible isogenic parent . The growth rate of three double-mutant strains parC Serine 79 to Tyrosine gyrA Serine 81 to Phenylanine, parC Serine 79 to Tyrosine, and Asparagine 83 to Phenylalanine were similar to the isogenic susceptible parent 1.16 (95% C.I . +/- 0.17), 0.99 (95% C.I . +/- 0.05), and 0.95 (95% C.I . +/- 0.05), respectively . These data suggest that mutation in the parC and gyrA genes may, on some occasions, not be associated with a physiological deficit.

Microb Drug Resist, 2002 Summer, 8(2), 129 - 32
Macrolide-resistance genes in clinical isolates of Streptococcus pyogenes; Cascone C et al.; Macrolide-resistance genes were investigated in 103 macrolide-resistant strains of Streptococcus pyogenes, isolated from children with pharyngotonsillitis . The presence of mef(A), erm(B), and erm(TR) genes was detected by PCR . mef(A) was found in 48 out of 103 (46.6%) strains, whereas erm(B) was detected in 43 isolates (41.7%) . All mef(A) strains showed a typical M phenotype (resistance to 14- and 15-membered macrolides, and sensitivity to lincosamides and streptogramin B), whereas erm(B) strains had the MLSB phenotype (resistance to macrolides, lincosamides, and streptogramin B antibiotics) . erm(TR) was found in 10 strains, always together with other resistance genes . In seven cases erm(TR) was associated with erm(B), and three cases with mef(A) . In two isolates with the M phenotype (1.9%), it was not possible to detect the presence of any of the three macrolide resistance genes tested . Inducible resistance to macrolides was shown for 24 out of the 53 MLSB strains . Analysis of macrorestriction fragment patterns by pulsed-field gel electrophoresis showed that erythromycin-resistant S . pyogenes are polyclonal, however each phenotype, MLSB and M, formed essentially homogeneous groups.

Infect Immun, 2002 Aug, 70(8), 4494 - 500
Identification and characterization of a novel heme-associated cell surface protein made by Streptococcus pyogenes; Lei B et al.; Analysis of the genome sequence of a serotype M1 group A Streptococcus (GAS) strain identified a gene encoding a previously undescribed putative cell surface protein . The gene was cloned from a serotype M1 strain, and the recombinant protein was overexpressed in Escherichia coli and purified to homogeneity . The purified protein was associated with heme in a 1:1 stoichiometry . This streptococcal heme-associated protein, designated Shp, was produced in vitro by GAS, located on the bacterial cell surface, and accessible to specific antibody raised against the purified recombinant protein . Mice inoculated subcutaneously with GAS and humans with invasive infections and pharyngitis caused by GAS seroconverted to Shp, indicating that Shp was produced in vivo . The blood of mice actively immunized with Shp had significantly higher bactericidal activity than the blood of unimmunized mice . The shp gene was cotranscribed with eight contiguous genes, including homologues of an ABC transporter involved in iron uptake in gram-negative bacteria . Our results indicate that Shp is a novel cell surface heme-associated protein.

Infect Immun, 2002 Aug, 70(8), 4389 - 98
Characterization of pit, a Streptococcus pneumoniae iron uptake ABC transporter; Brown JS et al.; Bacteria frequently have multiple mechanisms for acquiring iron, an essential micronutrient, from the environment . We have identified a four-gene Streptococcus pneumoniae operon, named pit, encoding proteins with similarity to components of a putative Brachyspira hyodysenteriae iron uptake ABC transporter, Bit . An S . pneumoniae strain containing a defined mutation in pit has impaired growth in medium containing the iron chelator ethylenediamine di-o-hydroxyphenylacetic acid, reduced sensitivity to the iron-dependent antibiotic streptonigrin, and impaired virulence in a mouse model of S . pneumoniae systemic infection . Furthermore, addition of a mutation in pit to a strain containing mutations in the two previously described S . pneumoniae iron uptake ABC transporters, piu and pia, resulted in a strain with impaired growth in two types of iron-deficient medium, a high degree of resistance to streptonigrin, and a reduced rate of iron uptake . Comparison of the susceptibilities to streptonigrin of the individual pit, piu, and pia mutant strains and comparison of the growth in iron-deficient medium and virulence of single and double mutant strains suggest that pia is the dominant iron transporter during in vitro and in vivo growth.

Infect Immun, 2002 Aug, 70(8), 4312 - 22
Streptococcus suis interactions with the murine macrophage cell line J774: adhesion and cytotoxicity; Segura M et al.; Streptococcus suis capsular type 2 is an important etiological agent of swine meningitis, and it is also a zoonotic agent . Since one hypothesis of the pathogenesis of S . suis infection is that bacteria enter the bloodstream and invade the meninges and other tissues in close association with mononuclear phagocytes, the objective of the present study was to evaluate the capacity of S . suis type 2 to adhere to macrophages . An enzyme-linked immunosorbent assay technique was standardized to simply and accurately measure the rate of bacterial attachment to phagocytic cells . Results were confirmed by plate counting . Adhesion was dependent on bacterial concentration and incubation time and was not affected by cytochalasin pretreatment of macrophages . Inhibition studies showed that the sialic acid moiety of the S . suis capsule would be, at least in part, responsible for bacterial recognition by macrophages . Serum preopsonization of bacteria increased adhesion levels . Complement would be partially implicated in the serum-enhanced binding of S . suis to cells . Adhesion varied among different S . suis type 2 isolates . However, high bacterial concentrations of several isolates were cytotoxic for cells, and these cytotoxic effects correlated with suilysin production . Indeed, hemolytic strain supernatants, as well as purified suilysin, reproduced cytotoxic effects observed with live bacteria, and these effects were inhibited by cholesterol pretreatment . Bacterial adhesion and cytotoxicity were confirmed by scanning and transmission electron microscopy . We hypothesize that attachment of bacteria to phagocytes could play an important role in the pathogenesis of S . suis infection by allowing bacterial dissemination and causing a bacteremia and/or septicemia . This interaction could also be related to the activation of the host inflammatory response observed during meningitis.

Infect Immun, 2002 Aug, 70(8), 4292 - 301
Comparison of alteration of cell surface carbohydrates of the chinchilla tubotympanum and colonial opacity phenotype of Streptococcus pneumoniae during experimental pneumococcal otitis media with or without an antecedent influenza A virus infection; Tong HH et al.; Experimental and clinical studies suggest that influenza A virus promotes Streptococcus pneumoniae-induced otitis media; however, the mechanism underlying this synergistic interaction has not been completely defined . In this study, glycoconjugate expression patterns were evaluated on the cell surface in the chinchilla eustachian tube (ET) lumen of a cohort challenged intranasally (i.n.) with S . pneumoniae type 6A, which is predominantly transparent and a cohort with an antecedent influenza A virus infection, followed by i.n . inoculation with S . pneumoniae . The labeling patterns obtained with six lectin probes revealed that the binding of Bandeiraea simplicifolia lectin II, succinylated wheat germ agglutinin, and peanut agglutinin were significantly increased in the lumenal surface of the ET in the cohort infected with both pathogens compared to the cohort inoculated with only S . pneumoniae, which indicated that N-acetylglucosamine (GlcNAc) and D-galactose residues were exposed . A significant decreased labeling with Sambucus nigra agglutinin in the combined influenza A virus and pneumococcus infection cohort suggested that there were few sialic acid residues remaining in the ET epithelium . In addition, the colonial opacity of S . pneumoniae during the disease course was examined . The opaque phenotype was predominant among the pneumococcus isolates from the middle-ear fluid in the cohort infected with the both pathogens . Together, these data suggest that the synergic effect of influenza A virus and S . pneumoniae on the changes of the carbohydrate moieties in the ET epithelium and that the selection of the opaque variant may facilitate the pneumococcal invasion of the middle ear.

Infect Immun, 2002 Aug, 70(8), 4226 - 38
Pathogenesis of pneumococcal pneumonia in cyclophosphamide-induced leukopenia in mice; Wang E et al.; Streptococcus pneumoniae pneumonia frequently occurs in leukopenic hosts, and most patients subsequently develop lung injury and septicemia . However, few correlations have been made so far between microbial growth, inflammation, and histopathology of pneumonia in specific leukopenic states . In the present study, the pathogenesis of pneumococcal pneumonia was investigated in mice rendered leukopenic by the immunosuppressor antineoplastic drug cyclophosphamide . Compared to the immunocompetent state, cyclophosphamide-induced leukopenia did not hamper interleukin-1 (IL-1), IL-6, macrophage inflammatory protein-1 (MIP-1), MIP-2, and monocyte chemotactic protein-1 secretion in infected lungs . Leukopenia did not facilitate bacterial dissemination into the bloodstream despite enhanced bacterial proliferation into lung tissues . Pulmonary capillary permeability and edema as well as lung injury were enhanced in leukopenic mice despite the absence of neutrophilic and monocytic infiltration into their lungs, suggesting an important role for bacterial virulence factors and making obvious the fact that neutrophils are ultimately not required for lung injury in this model . Scanning and transmission electron microscopy revealed extensive disruption of alveolar epithelium and a defect in surfactant production, which were associated with alveolar collapse, hemorrhage, and fibrin deposits in alveoli . These results contrast with those observed in immunocompetent animals and indicate that leukopenic hosts suffering from pneumococcal pneumonia are at a higher risk of developing diffuse alveolar damage.

Infect Immun, 2002 Aug, 70(8), 4083 - 91
Recurrent variable region gene usage and somatic mutation in the human antibody response to the capsular polysaccharide of Streptococcus pneumoniae type 23F; Zhou J et al.; Combinatorial cloning and expression library analysis were used to isolate human antibody Fab fragments specific for the capsular polysaccharide of Streptococcus pneumoniae serotype 23F . Thirty 23F-specific Fabs were isolated from seven vaccinated donors, and the sequences of the heavy (H)- and light (L)-chain variable regions were determined . All individuals utilized either the Vkappa A23 L chain, the Vkappa L6 L chain, or both chains in forming the 23F-specific combining site . Vkappa A23 L chains paired primarily with VH3-23 H chains . Vkappa L6 L chains were more promiscuous in heavy-chain usage between individuals . Both H and L chains were mutated, primarily in the complementarity-determining regions, compared to their closest germ line counterpart, suggesting a recall response that has undergone affinity maturation . H-chain isotypes were reflective of those found in the serum . Shared somatic modifications demonstrated that immunoglobulin G2 (IgG2) and IgA antibodies arose from the same somatically matured B cell . Our results indicate that the response to the serotype 23F pneumococcal capsular polysaccharide is oligoclonal within the individual, with one or two paratope families accounting for the majority of expressed antibody . We also determined that, in spite of the combinatorial diversity available to the immune system, the 23F-specific response is highly restricted at the population level, with the same two L-chain-determined paratope families recurring in all individuals . Lastly, analysis of the isolated Fabs indicate all have undergone extensive somatic mutation, as well as class switch, maturational events that presumably require the participation of T cells.

Infect Immun, 2002 Aug, 70(8), 4059 - 67
Microarray-based identification of htrA, a Streptococcus pneumoniae gene that is regulated by the CiaRH two-component system and contributes to nasopharyngeal colonization; Sebert ME et al.; Nasopharyngeal carriage is the reservoir from which most disease with Streptococcus pneumoniae arises . Survival as a commensal in this environment is likely to require a set of adaptations distinct from those needed to cause disease, some of which may be mediated by two-component signal transduction systems (TCSTS) . We examined the contributions of nine pneumococcal TCSTS to the process of nasopharyngeal colonization by using an infant rat model . Whereas deletions in all but one of these systems have been associated previously with a high degree of attenuation in a murine model of pneumonia, only the CiaRH system was necessary for efficient carriage . Transcriptional analysis by using microarray hybridization identified a locus consisting of two adjacent genes, htrA and spoJ, that was specifically and strongly downregulated in a DeltaciaRH-null mutant . A S . pneumoniae strain lacking the htrA gene encoding a putative serine protease, but not one lacking spoJ, showed decreased fitness in a competitive model of colonization, a finding consistent with this gene mediating a portion of the carriage deficit observed with the DeltaciaRH strain.

Clin Ther, 2002 Jun, 24(6), 838 - 50; discussion 837
Current issues on resistance, treatment guidelines, and the appropriate use of fluoroquinolones for respiratory tract infections; Bishai W; BACKGROUND: Community-acquired respiratory tract infections comprise a large percentage of diseases treated by primary care physicians, and rates of antimicrobial use for respiratory tract infections are increasing . The fluoroquinolones comprise a drug class with broad-spectrum activity against many of the key pathogens associated with community-acquired respiratory tract infections, including Streptococcus pneumoniae, and other significant pathogens, such as Staphylococcus aureus and Pseudomonas aeruginosa . While fluoroquinolones have gained popularity, the settings for their appropriate use in treating respiratory tract infections remain unclear . OBJECTIVE: In this article, the mechanisms of fluoroquinolone resistance in S . pneumoniae, treatment guidelines, and the mode of spread of resistance are reviewed . METHODS: The authors conducted a MEDLINE search for articles published from 1990 to the present . Search terms included Streptococcus pneumoniae, fluoroquinolones, and resistance . Articles were selected for inclusion based on their relevance to the objective of this review . RESULTS: Although 3 sets of treatment guidelines for community-acquired pneumonia (CAP) currently exist in the United States, a consensus for the role of fluoroquinolones in the outpatient management of CAP has not been achieved . Factors mitigating for restraint in the outpatient use of fluoroquinolones include concern for the spread of resistance to "innocent-bystander" organisms, such as S . aureus and P . aeruginosa, as well as possible inappropriate "trickle-down" use for other, less severe respiratory syndromes, such as bronchitis . CONCLUSION: Although the fluoroquinolones are potent agents against respiratory pathogens and have a clearly defined role in the treatment of hospitalized patients with CAP, their optimal role in the outpatient management of respiratory tract infections remains controversial.

J Med Assoc Thai, 2002 Mar, 85(3), 385 - 7
Streptococcus agalactiae meningitis in adults: report of two cases; Chotmongkol V et al.; Two cases of Streptococcus agalactiae meningitis in adults are reported . The first patient was a 40-year-old man who presented with acute fever, headache, stiffness of the neck and confusion . During treatment, he developed left hemiparesis from cerebral infarction and bilateral deafness . The other was an 80-year-old man who presented with acute confusion and stiffness of the neck . During treatment, he developed septic shock and generalized tonic-clonic convulsions . Diagnosis was established by latex agglutination of streptococcus B-antigen and confirmed by cerebrospinal fluid-culture later on . The first patient survived but continued to have deafness whilst the other died from septic shock.

Clin Infect Dis, 2002 Aug 1, 35(3), 268 - 76 Epub 2002 Jul 10.
Epidemiology of invasive group a streptococcus disease in the United States, 1995-1999; O'Brien KL et al.; Severe invasive group A streptococcal (GAS) disease is believed to have reemerged during the past 10-20 years . We conducted active, laboratory, population-based surveillance in 5 US states (total population, 13,214,992) . From 1 July 1995 through 31 December 1999, we identified 2002 episodes of invasive GAS (3.5 cases per 100,000 persons) . Rates varied by age (higher among those <2 or >/=65 years old), surveillance area, and race (higher among black individuals) but did not increase during the study period . The 5 most common emm types (1, 28, 12, 3, and 11) accounted for 49.2% of isolates; newly characterized emm types accounted for 8.9% of isolates . Older age; presence of streptococcal toxic shock syndrome, meningitis, or pneumonia; and infection with emm1 or emm3 were all independent predictors of death . We estimate that 9600-9700 cases of invasive GAS disease occur in the United States each year, resulting in 1100-1300 deaths.

Am J Obstet Gynecol, 2002 Jul, 187(1), 137 - 44
Antimicrobial factors in the cervical mucus plug; Hein M et al.; OBJECTIVE: The cervical mucus plug is positioned between the microbe-rich vagina and the normally sterile uterine cavity, which suggests a host defense function, but few relevant data are available . We analyzed the composition and antimicrobial activity of cervical mucus plugs . STUDY DESIGN: Cervical mucus plugs were collected from healthy women at delivery . Groups of plugs were randomly selected for electrolyte analysis, antimicrobial activity assays against group B Streptococcus, Escherichia coli, Candida albicans, and assays of known antimicrobial polypeptides . RESULTS: Both intact cervical mucus plugs and their aqueous extracts exhibited antimicrobial activity against aerobic microbes, in the order of potency: group B Streptococcus > E coli > C albicans . Semiquantitative Western blotting of extracts showed that secretory leukoprotease inhibitor, lysozyme, lactoferrin, and neutrophil defensins were present at concentrations that were sufficient for antimicrobial activity . CONCLUSION: The cervical mucus plug is not only a mechanical but also a chemical barrier to infection that ascends from the vagina.

FEMS Microbiol Lett, 2002 Jul 2, 212(2), 151 - 7
Identification and analysis of the amylase-binding protein B (AbpB) and gene (abpB) from Streptococcus gordonii; Li L et al.; The binding of salivary amylase to Streptococcus gordonii has previously been shown to involve a 20-kDa amylase-binding protein (AbpA) . S . gordonii also releases an 82-kDa protein into the supernatant that binds amylase . To study this 82-kDa component, proteins were precipitated from bacterial culture supernatants by the addition of acetone or purified amylase . Precipitated proteins were separated by SDS-PAGE and transferred to a sequencing membrane . The P2 kDa band was then sequenced, yielding a 25 N-terminal amino acid sequence, CGFIFGRQLTADGSTMFGPTEDYP . Primers derived from this sequence were used in an inverse PCR strategy to clone the full-length gene from S . gordonii chromosomal DNA . An open reading frame of 1959 bp was noted that encoded a 652 amino acid protein having a predicted molecular mass of 80 kDa . The first 24 amino acid residues were consistent with a hydrophobic signal peptide, followed by a 25 amino acid N-terminal sequence that shared identity (24 of 25 residues) with the amino acid sequence of purified AbpB . The abpB gene from strains of S . gordonii was interrupted by allelic exchange with a 420-bp fragment of the abpB gene linked to an erythromycin cassette . The 82-kDa protein was not detected in supernatants from these mutants . These abpB mutants retained the ability to bind soluble amylase . Thus, AbpA, but not AbpB, appears sufficient to be the major receptor for amylase binding to the streptococcal surface . The role of AbpB in bacterial colonization remains to be elucidated.

J Emerg Med, 2002 May, 22(4), 357 - 66
Fulminant infection and toxic shock syndrome caused by Streptococcus pyogenes; Fox KL et al.; Two patients presented to the Emergency Department (ED) with features of toxic shock syndrome, including hypotension, acute respiratory distress syndrome (ARDS), renal and hepatic insufficiency and disseminated intravascular coagulation (DIC) . Computed tomography (CT) scan identified the source of infection in one patient . At laparotomy, pelvic peritonitis and massive edema of the pelvic retroperitoneal tissue was found . The other patient had myonecrosis of the forearm necessitating amputation . Intra-operative cultures of tissue in each case yielded Streptococcus pyogenes, Group A . These patients were treated early with clindamycin and intensive supportive care as well as surgery, and both made a full recovery . Because of the necessity of early recognition of the varied presentation of these infections, the clinical features as well as essential interventions are emphasized . We review the pathophysiology of invasive Group A streptococcal infection to increase awareness of these uncommon but fulminant and often lethal infections.

Epidemiol Infect, 2002 Jun, 128(3), 397 - 404
Distribution of emm genotypes and superantigen genes of Streptococcus pyogenes isolated in Japan, 1994-9; Murakami J et al.; The purpose of this study was to examine characteristic profiles of Streptococcus pyogenes clinical isolates isolated in Japan during 1994-9 . Genotyping of the M protein (emm typing) revealed that emm types 12 and 28 were the most common among 316 isolates . Most of the emm12 isolates were isolated from mucosa, while emm58 and emm89 were from skin . Moreover, the emm3 isolates were dominant in invasive infections . The distribution of 6 superantigen genes showed that all isolates harboured the mf gene and many had the speG gene . Invasive isolates were shown to have the ssa gene at a higher rate (76%) than noninvasive (37%) . The distribution of superantigens was significantly different between emm types, but not between isolation sites . These results suggest that the distribution of emm types is related to isolation site, whereas superantigen distribution is related to clinical features of S . pyogenes infections.

Epidemiol Infect, 2002 Jun, 128(3), 391 - 6
Streptococcus pyogenes prtFII, but not sfbI, sfbII or fbp54, is represented more frequently among invasive-disease isolates of tropical Australia; Delvecchio A et al.; Streptococcus pyogenes (group A streptococcus) strains may express several distinct fibronectin-binding proteins (FBPs) which are considered as major streptococcal adhesins . Of the FBPs, SfbI was shown in vitro to promote internalization of the bacterium into host cells and has been implicated in persistence . In the tropical Northern Territory, where group 4 streptococcal infection is common, multiple genotypes of the organism were found among isolates from invasive disease cases and no dominant strains were observed . To determine whether any FBPs is associated with invasive disease propensity of S . pyogenes, we have screened streptococcal isolates from bacteraemic and necrotizing fasciitis patients and isolates from uncomplicated infections for genetic endowment of 4 FBPs . No difference was observed in the distribution of sfbII, fbp54 and sfbI between the blood isolates and isolates from uncomplicated infection . We conclude that the presence of sfbI does not appear to promote invasive diseases, despite its association with persistence . We also show a higher proportion of group A streptococcus strains isolated from invasive disease cases possess prtFII when compared to strains isolated from non-invasive disease cases . We suggest that S . pyogenes may recruit different FBPs for different purposes.

Dis Aquat Organ, 2002 Jun 3, 49(3), 165 - 70
Streptococcus iniae infections in Red Sea cage-cultured and wild fishes; Colorn A et al.; Streptococcus iniae was isolated from 2 moribund wild Red Sea fishes, Pomadasys stridens (Pomadasyidae) and Synodus variegatus (Synodontidae), both collected in shallow waters along the Israeli coast of the Gulf of Eilat . The site is approximately 2 km from a mariculture cage farm in which streptococcal infections were diagnosed in previous years in the red drum Sciaenops ocellatus . This is the first report of S . iniae in Red Sea fishes . Biochemical and molecular similarities between the isolates from cultured fishes and those from the wild specimens suggest that a single strain is involved, and that 'amplification' and dispersal of this pathogen from captive to feral fishes have occurred . At the molecular level, the pathogen is different from the S . iniae isolates that have been afflicting the Israeli freshwater aquaculture in recent years . Although S . iniae prevalence in the wild fish populations of the area remains to be determined, the northernmost region of the Gulf of Eilat, virtually landlocked and with generally calm seas and weak currents, seems to be particularly vulnerable to the impact of diseases that develop in this mariculture system.

Phytother Res, 2002 Jun, 16(4), 336 - 9
Activity of essential oils of three Micromeria species (Lamiaceae) against micromycetes and bacteria; Marinkovic B et al.; The chemical composition of essential oils from three Micromeria species: M . dalmatica Benth., M . albanica (Griceb . ex K . Mal) Silic and M . thymifolia (Scop.) Fritsch were investigated by GC and GC-MS and their antibacterial and antifungal activities against seven fungal and six bacterial species were evaluated . Biological assays showed strong fungitoxicity of oils from all three Micromeria spp., particularly M . albanica, against all fungi tested . Essential oils of these species also exerted antibacterial effect against Streptococcus aureus, Escherichia coli, Bacillus subtilis and Micrococcus luteus at low concentrations . Higher concentrations of essential oil of M . albanica and M . dalmatica were active against Gram-negative Pseudomonas aeruginosa, which could be due to the high content of piperitenone oxide .

J Infect Chemother, 2002 Jun, 8(2), 134 - 7
Trends in antimicrobial susceptibility of the Streptococcus milleri group; Yamamoto N et al.; A collection of 114 clinical Streptococcus milleri group (SMG) strains at the Ryukyu University Hospital obtained in 1999 and 2000, was identified and tested for susceptibility to 12 antibiotics . The percentage of strains with intermediate susceptibility to penicillin G was relatively high (14%) . Cefaclor and cefotiam, with a MIC 90 of 2 microg/ml, were less active than cefotaxime . Strains nonsusceptible to erythromycin, clindamycin, and azithromycin were found with a frequency of 8%, 5%, and 4%, respectively . Almost all of the SMG strains were susceptible to fluoroquinolones (except for 1% of the strains nonsusceptible to levofloxacin), and sitafloxacin (DU-6859a) was the most active agent among the 12 tested antibiotics.

Eur J Pediatr, 2002 Jul, 161(7), 368 - 72 Epub 2002 Jun 04.
Familial isolated congenital asplenia: a rare, frequently hereditary dominant condition, often detected too late as a cause of overwhelming pneumococcal sepsis . Report of a new case and review of 31 others; Gilbert B et al.; Congenital isolated asplenia may arise as a minor form of situs abnormalities or result from an unrelated specific defect of spleen development . It is a rare life-threatening condition and pneumococcal sepsis is often the first sign of the disease . We report on the case of a deceased 11-month-old girl and her father who developed recurrent pneumococcal meningitis . The fatal evolution in the girl was due to Streptococcus pneumoniae serotype 23 with intermediate penicillin sensitivity 4 h after amoxicillin (100 mg/kg i.v.) administration . Establishing the diagnosis of congenital isolated asplenia in the case of pneumococcal sepsis can be achieved by performing two easy and non-invasive investigations: searching for Howell-Jolly bodies on blood smears and performing ultrasound examination of the abdomen to look for the spleen . In the case of congenital isolated asplenia, use of appropriate prophylaxis could save the lives of affected children . Our review of the literature yielded 31 cases of congenital isolated asplenia . Thirteen were sporadic and 18 were familial cases involving eight families . CONCLUSION: in the case of Streptococcus pneumoniae sepsis, a systematic search for Howell-Jolly bodies on blood smears and ultrasound examination of the abdomen for the presence of asplenia should be mandatory to detect isolated congenital asplenia . If asplenia is found, potentially life-saving antibiotic prophylaxis and pneumococcal vaccination should be initiated.

Arch Pediatr, 2002 Jun, 9(6), 606 - 9
{Lung abscess due to Mycoplasma pneumoniae in an adolescent}; Micheau P et al.; Pulmonary abscess is an uncommon complication of pneumonia in children . Pyogenes, in particular Staphylococcus aureus or Streptococcus pneumoniae are the principal responsible bacteria . Mycoplasma pneumoniae is rarely the cause . CASE REPORT: A 14-year-old child was hospitalized with right thoracic pain . The patient was non-febrile and had a recent history of moderate infection . He was receiving antibiotic (macrolide) and non-steroidal anti-inflammatory therapy . CT scan confirmed a mid-lobe abscess in the right lung . Interruption of therapy resulted in fever and increase in C-reactive level with hyperleucocytosis, suggesting that the abscess was caused by a bacterial infection . The child's general condition and the radiographic picture improved with combined antibiotic therapy with amoxycillin and clavulanic acid, aminoglycosides and macrolides . The suspected diagnostic of M . pneumoniae was confirmed by increased IgM antibodies for M . pneumoniae . Recovery was complete two months later without sequelae . COMMENT: Pulmonary abscess is a rare complication of M . pneumoniae infection in children . This complication should be considered when the general condition does not improve despite appropriate early treatment of a pneumonia, as in the case of our patient.

Diagn Microbiol Infect Dis, 2002 Jul, 43(3), 207 - 17
Comparative activity of gatifloxacin and other antibiotics against 4009 clinical isolates of Streptococcus pneumoniae in the United States during 1999-2000; White RL et al.; The susceptibility of 4009 recent clinical isolates of Streptococcus pneumoniae to gatifloxacin, levofloxacin, ciprofloxacin, penicillin, ceftriaxone and azithromycin was determined . Overall rates of susceptibility to these agents were 99.4, 98.7, 71.2, 55.2, 80.9, and 71.3%, respectively . Resistance to all tested agents was associated with penicillin resistance . Of penicillin nonsusceptible isolates, 36% were resistant . Resistance to the fluoroquinolones was unusual and gatifloxacin generally appeared to be four-fold more active than levofloxacin or ciprofloxacin . Multidrug resistant S . pneumoniae accounted for 6.2% of this sample . The lowest rate of susceptibility to non-fluoroquinolone antibiotics was observed in isolates from the South region of the United States, which appeared to be explained by both the proportion of and the inherently higher MICs of certain types of isolates.

Microbiology, 2002 Jul, 148(Pt 7), 2065 - 77
Pattern searches for the identification of putative lipoprotein genes in Gram-positive bacterial genomes; Sutcliffe IC et al.; N-terminal lipidation is a major mechanism by which bacteria can tether proteins to membranes and one which is of particular importance to Gram-positive bacteria due to the absence of a retentive outer membrane . Lipidation is directed by the presence of a cysteine-containing 'lipobox' within the lipoprotein signal peptide sequence and this feature has greatly facilitated the identification of putative lipoproteins by gene sequence analysis . The properties of lipoprotein signal peptides have been described previously by the Prosite pattern PS00013 . Here, a dataset of 33 experimentally verified Gram-positive bacterial lipoproteins (excluding those from Mollicutes) has been identified by an extensive literature review . The signal peptide features of these lipoproteins have been analysed to create a refined pattern, G+LPP, which is more specific for the identification of Gram-positive bacterial lipoproteins . The ability of this pattern to identify probable lipoprotein sequences is demonstrated by a search of the genome of Streptococcus pyogenes, in comparison with sequences identified using PS00013 . Greater discrimination against likely false-positives was evident from the use of G+LPP compared with PS00013 . These data confirm the likely abundance of lipoproteins in Gram-positive bacterial genomes, with at least 25 probable lipoproteins identified in S . pyogenes

Microbiology, 2002 Jul, 148(Pt 7), 2055 - 64
Bovine immunoglobulin A (IgA)-binding activities of the surface-expressed Mig protein of Streptococcus dysgalactiae; Song XM et al.; The Mig protein of Streptococcus dysgalactiae is a type III immunoglobulin G (IgG)-binding protein, expressing IgG- and alpha2-macroglobulin (alpha2-M)-binding receptors . This study showed that the Mig protein also displays binding activities to bovine immunoglobulin A (B-IgA) . Biotin-labelled bovine serum IgA bound immobilized recombinant Mig and alpha2-M receptors derived from Mig, as well as the native Mig extracted from the surface of S . dysgalactiae strain SDG8 and the alpha(2)-M receptor released from the isogenic mig mutant strain Mig8-Mt, as determined by Western blotting and ELISA . There was no B-IgA binding activity to the immobilized IgG receptor derived from Mig or the proteins in the culture supernatant from the mig mutant strain Mig7-Mt, in which expression of Mig or Mig-related peptides on the cell surface was completely abolished . In a reciprocal experiment, biotin-labelled Mig was found to bind immobilized bovine serum IgA but not human IgA (H-IgA) . The binding of Mig to bovine serum IgA was competitively inhibited by unlabelled Mig, intact and truncated alpha(2)-M receptors, and bovine serum IgA, but not by the Mig-IgG receptor, H-IgA or B-IgG . The binding of Mig and partially purified bovine secretory IgA (B-sIgA) was also characterized by Western blotting . Membrane-immobilized B-sIgA did not react with the biotin-labelled Mig, whereas soluble B-sIgA showed binding activity to the immobilized alpha2-M receptor of Mig . It is therefore concluded that the 11 kDa N-terminal region of the alpha2-M receptor of the S . dysgalactiae Mig protein specifically binds soluble and immobilized bovine serum IgA, as well as soluble B-sIgA . This is believed to be the first report of a B-IgA-binding protein in S . dysgalactiae.

Microbiology, 2002 Jul, 148(Pt 7), 2045 - 53
The genes encoding virulence-associated proteins and the capsule of Streptococcus pneumoniae are upregulated and differentially expressed in vivo; Ogunniyi AD et al.; The polysaccharide capsule of Streptococcus pneumoniae and several well-characterized virulence proteins are known to contribute to the pathogenesis of pneumococcal disease . However, there is a paucity of data on the expression of their respective genes in vivo . In this study, the relative abundance of the mRNA transcripts of the genes encoding pneumolysin (ply), pneumococcal surface protein A (pspA), pneumococcal surface antigen A (psaA) and choline-binding protein A (cbpA), and of the first gene of the capsular polysaccharide biosynthesis locus (cps2A), was measured in virulent type 2 pneumococci harvested from the blood of BALB/c mice at 12 h and 24 h following intraperitoneal infection . The mRNA levels were then compared, using relative quantitative RT-PCR, with those present in organisms grown in serum broth . The expression of ply was upregulated threefold at 12 h, and 10-fold at 24 h post-infection; the expression of pspA and psaA was upregulated threefold and fivefold, respectively, at 12 h post-infection . Interestingly, the expression of pspA was 36-fold higher at 24 h post-infection whereas the expression of cps2A was upregulated approximately fourfold at 12 and 24 h post-infection . However, cbpA mRNA levels remained comparable in vivo and in vitro . When organisms were grown in whole blood or THY broth, the relative expression of these genes in the two growth media also differed markedly . This work provides direct molecular evidence that known virulence-associated genes of S . pneumoniae are differentially expressed in vivo . Data on the relative expression of these genes in different growth media also suggests that the regulation of expression of these genes is highly complex and multifactorial.

J Leukoc Biol, 2002 Jul, 72(1), 163 - 6
TGF-beta1 and IFN-gamma cross-regulate antigen presentation to CD4 T cells by macrophages; Delvig AA et al.; We studied the interaction of transforming growth factor-beta1 (TGF-beta1) and interferon-gamma (IFN-gamma) in regulating Ag presentation in macrophages . TGF-beta1 blocked, and IFN-gamma enhanced Ag presentation of two T cell epitopes from the group A streptococcal M protein processed from viable Streptococcus pyogenes . Consistent with the functional data, TGF-beta1 reduced the constitutive expression of MHC class II transactivator (CIITA), MHC class II (MHC-II), invariant chain, and DO mRNA, whereas IFN-gamma up-regulated the expression of CIITA and MHC-II mRNA without affecting invariant chain or DO mRNA . However, neither cytokine affected DM mRNA expression . Treatment of macrophages with the two cytokines in combination showed that TGF-beta1 down-regulated IFN-gamma-mediated enhancement of antigen presentation and inhibited IFN-gamma-inducible CIITA and MHC-II class II mRNA expression . The effect of TGF-beta1 on Ag presentation was shown to be independent of the surface expression of CD80, CD86, or CD40 costimulatory molecules by flow cytometry . Our results show that TGF-beta1 and IFN-gamma cross-regulate Ag presentation by influencing the transcription of several genes associated with antigen presentation function, which may represent an important mechanism limiting T cell activation during an immune response.

J Infect, 2002 May, 44(4), 267 - 9
A case of retropharyngeal abscess caused by penicillin-resistant Streptococcus pneumoniae; Kobayashi KI et al.; We report here a case of a 1-year-old girl with retropharyngeal abscess caused by penicillin-resistant Streptococcus pneumoniae (PRSP) . Computed tomography disclosed a retropharyngeal mass lesion (4 cm x 3 cm in diameter), and the diagnosis was confirmed by needle aspiration of the retropharyngeal space, which yielded PRSP . To our knowledge, this is the first report of a young subject in whom retropharyngeal abscess was caused by this organism . Retropharyngeal abscess is most common in children younger than 3 or 4 years of age, during which period a high carriage rate of PRSP is also shown . This patient was successfully treated with panipenem/betamipron .

J Basic Clin Physiol Pharmacol, 2002, 13(1), 33 - 40
The role of free oxygen radicals in experimental otitis media; Doner F et al.; Free oxygen radicals (FORs); have been implicated as important pathologic mediators in many diseases . Under physiological conditions FORs are part of normal regulatory circuits and neutralized by antioxidants, but an increased flux of FORs can cause tissue damage . Infections are one cause of increased FORs production . An important mechanism of tissue damage produced by FORs is the peroxidation of membrane lipids, which can be estimated by malondialdehyte (MDA) levels . The purpose of this study was to determine in 24 albino rabbits whether FORs play a role in the pathogenesis of otitis media experimentally induced by inoculating Streptococcus pneumonia into the right ear, with the left ear serving as a control . We examined the mucosa of each middle ear histopathologically and measured MDA levels in mucosa and serum . Serum MDA levels in infected rabbits were significantly higher than those in preoperative blood specimens (p<0.05) . The MDA levels in mucosa were significantly higher in infected ears than in control ears (p<0.01) . In the experimentally infected group, a correlation was found between MDA levels in serum and mucosa (p<0.05) . In conclusion, serum and mucosa MDA indicating FORs production increased significantly in experimental otitis media . We considered that FORs might play a role in tissue damage caused by otitis media.

Arch Ophthalmol, 2002 Jul, 120(7), 960 - 2
ELVIS: a new 24-hour culture test for detecting herpes simplex virus from ocular samples; Kowalski RP et al.; OBJECTIVE: To compare ELVIS (Enzyme Linked Virus Inducible System) (BioWhittaker, Walkersville, Md), a new, simple, 24-hour cell culture test for detecting herpes simplex virus (HSV), with standard cell culture and Herpchek (NEN, Boston, Mass) for detecting HSV in ocular specimens . METHODS: Retrospectively, 36 true-positive frozen-stock ocular samples that were cell-culture positive for HSV, and 25 true-negative samples (varicella-zoster virus, adenovirus, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus viridans) were tested with ELVIS . Herpchek was processed at the time of initial clinical laboratory testing . Prospectively, 422 patients were tested for HSV with standard cell culture, ELVIS, and Herpchek . The sensitivity, specificity, positive and negative predictive values, and efficacy of ELVIS based on positive and negative cell cultures were determined . RESULTS: Retrospectively, ELVIS was 86.1% sensitive (31/36), 100% specific (25/25), and 91.8% efficient (56/61) . The positive predictive value was 100% (31/31), and the negative predictive value was 83.3% (25/30) . The sensitivity of ELVIS was equivalent to Herpchek (80.5%, 29/36) (P =.53) . Prospectively, the sensitivity of ELVIS (84.8%, 28/33) was equivalent to that of Herpchek (84.8%, 28/33) . CONCLUSIONS: ELVIS is an easy HSV diagnostic test that can provide faster positive culture results than standard cell culture, and it is equally sensitive but less time-consuming than Herpchek.

J Dent Res, 2002 Jun, 81(6), 376 - 9
Attenuation of glucan-binding protein C reduces the cariogenicity of Streptococcus mutans: analysis of strains isolated from human blood; Nakano K et al.; A blood isolate of Streptococcus mutans strain TW871 shows relatively low homology with MT8148, a reference oral isolate strain, and lacks the serotype-specific polysaccharide antigen, suggesting that other cell-surface structures correlate with cariogenicity . We compared cariogenicity of TW871 with MT8148 (serotype c) and blood isolate TW964 (serotype f) in rats . Strain TW871 showed significantly lower cariogenicity than MT8148 or TW964 and expressed significantly lower sucrose-independent cellular adhesion to saliva-coated hydroxyapatite and dextran-binding activity than strain MT8148 . Strains TW871 and TW964 showed a defect in the gbpA gene by Southern hybridization analysis, while sequencing analysis revealed gbpC variation in TW871 . These results suggest that variation in GbpC may alter cellular adherence properties and can be correlated with the cariogenicity of S . mutans in this strain.

J Antimicrob Chemother, 2002 Jul, 50(1), 43 - 50
Streptococcus pneumoniae bacteraemia in Belgium: differential characteristics in children and the elderly population and implications for vaccine use; Flamaing J et al.; The characteristics of bacteraemia with Streptococcus pneumoniae in children (0-4 years) and the elderly (> or =60 years) were compared over a 7 year period (1994-2000) . Of a total of 7927 isolates of invasive S . pneumoniae studied in the national reference laboratory, 74% (n = 5837) were blood isolates . Of these 5837 S . pneumoniae bacteraemias, 843 (14%) occurred in children and 3144 (54%) in the elderly . The prevalence of penicillin resistance (MIC > or = 0.1 mg/L) in bacteraemic isolates rose from 8.2% to 18.9% (P = 0.03) in children and from 5.1% to 16.35% (P = 0.001) in the elderly over the study period . The prevalence of erythromycin resistance (MIC > or= 1 mg/L) in bacteraemic isolates was significantly higher in children than in the elderly (44.7% versus 25.7%, P = 0.001) and rose significantly over the 7 year period in the elderly (18.6-33.65%, P = 0.001) . There were more serogroups and serotypes (SGTs) among the bacteraemic isolates obtained from the elderly compared with children (36 versus 26, P = 0.03) . SGTs 6, 14, 18 and 19 cause significantly more bacteraemia in children than in the elderly . The opposite is true for SGTs 3, 7, 8, 9, 11, 12, 15, 20, 22 and 35 . The new 7, 9 and 11 valent conjugate vaccine formulations cover significantly more bacteraemic SGTs in children than in the elderly (82%, 89.5% and 92% versus 55.5%, 65% and 77.5%, respectively; P = 0.001) . The 23 valent polysaccharide vaccine provides a theoretical coverage of 95% in the elderly population . Our data indicate consideration of a vaccination strategy in the elderly population that combines the efficacy of conjugate vaccines with the broad coverage of the 23 valent polysaccharide vaccine.

Am J Gastroenterol, 2002 Jun, 97(6), 1476 - 9
Spontaneous bacterial peritonitis caused by Streptococcus bovis: case series and review of the literature; Vilaichone RK et al.; Streptococcus bovis is the rare cause of spontaneous bacterial peritonitis in decompensated cirrhosis . S . bovis bacteremia has long been known to be associated with colon cancer . We describe seven patients and review the seven previous reports of spontaneous bacterial peritonitis patients with S . bovis infection . Most of the patients had cirrhosis and presented with fever, abdominal pain, abdominal distention, and jaundice . Colonic adenomatous polyps with dysplastic change were found in 18.2% of the patients . The approach to this group of patients requires diagnostic paracentesis, blood cultures, ascitic fluid culture, and treatment with antimicrobial agents . Intravenous penicillin is still the antimicrobial agent of first choice (mean minimum inhibitory concentration for penicillin = 0.05 microg/ml) . S . bovis is an infrequent cause of spontaneous bacterial peritonitis . The physician could make a case that colonoscopy is not needed because the patient is very sick and the possibility of GI pathology, especially colonic lesions, has been low . However, it may be that colonoscopy should be done if there are clinical suggestions to do so or the patient is well enough to withstand surgery.

Pediatrics, 2002 Jul, 110(1 Pt 1), 1 - 6
Clinical characteristics of children with complicated pneumonia caused by Streptococcus pneumoniae; Tan TQ et al.; OBJECTIVE: The frequency of children who are hospitalized with pneumococcal pneumonia complicated by necrosis, empyema/complicated parapneumonic effusion, and lung abscess seems to be increasing . The factors that contribute to this increase are unclear; therefore, the objective of this study was to describe and compare the relative frequency, clinical characteristics, and outcome of hospitalized children with complicated pneumonia with those of children with uncomplicated pneumonia caused by Streptococcus pneumoniae in the era of antibiotic resistance . METHODS: A multicenter, retrospective study of 8 children's hospitals in the United States was undertaken . A total of 368 children who were hospitalized with pneumococcal pneumonia identified from patients enrolled in the US Pediatric Multicenter Pneumococcal Surveillance Study over the period from September 1, 1993, to January 31, 2000 were studied . Demographic and clinical variables, antibiotic susceptibility, pneumococcal serotypes, antimicrobial therapy, and clinical outcome in hospitalized children with complicated versus uncomplicated pneumococcal pneumonia were measured . RESULTS: A total of 368 patients with pneumococcal pneumonia were identified . Of the 368 isolates, 47 (12.8%) were intermediate and 37 (10.1%) were resistant to penicillin; 18 (5%) were intermediate to ceftriaxone, and 9 (2.5%) were resistant to ceftriaxone . A total of 133 patients met the criteria for complicated pneumonia and had a chest tube placed; 56 of these patients subsequently underwent decortication . The proportion of hospitalized patients with complicated pneumococcal pneumonia increased progressively over the study period from 22.6% in 1994 to 53% in 1999 . Patients with complicated disease were older (median age: 45 vs 27 months) and significantly more likely to be of white race and have chest pain on presentation compared with patients with uncomplicated disease . Patients who had complicated disease and underwent decortication were more likely to have pleural fluid lactate dehydrogenase levels of >7500 IU/L compared with those patients who had chest tube placement alone . Fifty-three percent of children who were > or =61 months of age and were hospitalized had complicated pneumonia . This group of children accounted overall for 42% of the patients with complicated pneumonia, 48.2% of the patients who subsequently underwent decortication, and 44% of the patients who had received a course of antibiotics before diagnosis . Pneumococcal serotypes 1, 6, 14, and 19 were the most prevalent serotypes causing disease, with serotype 1 causing 24.4% of the complicated cases versus 3.6% of the uncomplicated cases . Ninety-eight percent of the patients in both groups recovered from their pneumonia . Antibiotic resistance was not found to be more prevalent in those patients with complicated disease . CONCLUSIONS: The relative frequency of complicated disease in hospitalized children with pneumococcal pneumonia is increasing . Patients with complicated pneumococcal disease were older and significantly more likely to be of white race compared with those patients with uncomplicated disease . Pneumococcal serotype 1 caused significantly more disease in patients with complicated versus uncomplicated pneumonia . Patients with complicated disease were not more likely to be infected with an antibiotic-resistant isolate.

Arch Surg, 2002 Jul, 137(7), 845 - 9
Determinants for successful percutaneous image-guided drainage of intra-abdominal abscess; Cinat ME et al.; HYPOTHESIS: Characteristics of intra-abdominal abscess can be used to predict successful outcome for percutaneous catheter drainage (PCD) . METHODS: We performed a multicenter prospective study of patients who had intra-abdominal infections treated with PCD and intravenous antibiotics . Multivariate regression analysis determined predictors of successful outcome . RESULTS: The study included 96 patients (59% men; mean +/- SD age, 48 +/- 17 years; mean +/- SD Acute Physiology and Chronic Health Evaluation II score, 7.4 +/- 4.9) . Postoperative abscess was present in 53% of patients . Isolated microorganisms included Bacteroides species (17%), Escherichia coli (17%), Streptococcus species (14%), Enterococcus species (10%), and fungi (11%) . Single abscesses were present in 83% of patients . Computed tomographic guidance was used for drainage in 80% of patients, and ultrasound was used in 20% . The duration of abscess drainage was less than 14 days in 64% . Complete resolution of the infection with a single treatment of PCD was achieved in 67 patients (70%), and with a second attempt in 12 (12%) . Thirty-three patients (34%) had PCD for the resolution of intra-abdominal sepsis prior to an elective, definitive procedure . Open drainage as a result of PCD failure was required in 15 (16%) and was more likely in patients with yeast (P<.001) or a pancreatic process (P =.02) . Postoperative abscess (P =.04) was an independent predictor of successful outcome . CONCLUSIONS: Percutaneous catheter drainage of intra-abdominal infections was effective with a single treatment in 70% of patients and increased to 82% with a second attempt . A successful outcome is most likely with abscesses that are postoperative, not pancreatic, and not infected with yeast . Percutaneous catheter drainage is now a commonly used staging method for the resolution of intra-abdominal sepsis prior to corrective operation.

Matern Child Health J, 2002 Jun, 6(2), 107 - 14
Integrated monitoring of a new group B streptococcal disease prevention program and other perinatal infections; Schuchat A et al.; OBJECTIVE: To determine levels of prenatal screening for several infections, intrapartum recognition of risk factors, and prophylaxis against mother-to-child transmission of group B streptococcus . METHODS: Review of stratified random sample of hospital records for deliveries in Connecticut during 1996 . SUDAAN analysis was used to adjust for the complex survey design, and weighting adjusted for the probability of being sampled and nonresponse . RESULTS: Of 992 records requested, 868 (88%) were abstracted and analyzed . Thirty-six percent of women had prenatal screening for group B streptococcus and 26% had been tested for human immunodeficiency virus (HIV), while 97-99% of women had been screened prenatally for hepatitis B surface antigen, rubella, and syphilis . Of those women tested, 17% were detected as group B streptococcus carriers, and 78% of these received intrapartum antibiotic prophylaxis . Among women who were not screened for group B streptococcus prenatally, 22% met risk-based criteria for prophylaxis, but only 45% of these received intrapartum prophylaxis . Among unscreened women with a risk factor, those with shorter hospital stays prior to delivery, admitted on evening or night shifts, or who delivered on the weekend were significantly less likely to receive intrapartum prophylaxis . CONCLUSION: In 1996, the majority of women who delivered in Connecticut were not tested prenatally for group B streptococcus and the majority of those not tested in whom there was an indication for prophylaxis were not treated . Compliance with group B streptococcus prevention recommendations can be improved through increased prenatal testing and/or better recognition of risk-based criteria for intrapartum prophylaxis.

Rev Med Chir Soc Med Nat Iasi, 2001 Oct-Dec, 105(4), 773 - 7
Sensitivity and resistance to antibiotics of Streptococcus pneumoniae involved in severe infections (1990-2000); Turcu T et al.; S . pneumoniae implicated in severe infections presents now a high frequency of the resistant strains to Penicillin G or multiresistance in the whole world . Our study on 136 strains of invasive pneumococcus isolated in the last 10 years showed a medium resistance to penicillin of 22.8% with yearly variations . The resistance to Rifampin, Cloramphenicol and Eritromycin was of 4.4%, 7.8% and 8.0% . The treatment of pneumococcal infections must be adapted to actual antibiotypes . These results present therapeutic implications.

Blood, 2002 Jul 15, 100(2), 509 - 16
A role for glycoprotein Ib in Streptococcus sanguis-induced platelet aggregation; Kerrigan SW et al.; Numerous studies have implicated bacteria in cardiovascular disease, but there is a paucity of information on the mechanism involved . In this study we show how the common oral bacterium Streptococcus sanguis can directly interact with platelets, resulting in activation and aggregate formation . Platelet aggregation was dependent on glycoprotein IIb/IIIa (GPIIb/IIIa) and thromboxane . Platelets could also directly bind to S sanguis, but this interaction was not inhibited by GPIIb/IIIa antagonists . Antibodies to GPIb could inhibit both platelet aggregation and platelet adhesion to bacteria . This suggested a direct interaction between GPIb and S sanguis; however, this interaction did not require von Willebrand factor, the normal ligand for GPIb . By use of a range of monoclonal antibodies to GPIb and the enzyme mocharagin, which cleaves GPIb at amino acid 282, the interaction was localized to a region within the N-terminal 1-225 portion of GPIbalpha . Furthermore S sanguis failed to induce aggregation of platelets from a patient with Bernard-Soulier disease, the organism bound to Chinese hamster ovary cells transfected with the GPIbalpha gene but did not bind to mock-transfected cells and biotin-labeled S sanguis cells bound to purified GPIb in ligand blots . It is suggested that the interaction between S sanguis and GPIb is important in the pathogenesis of infective endocarditis and may also play a contributory role in some cases of myocardial infarction.

Am J Respir Crit Care Med, 2002 Jul 1, 166(1), 53 - 60
Very late antigen-4 in CD18-independent neutrophil emigration during acute bacterial pneumonia in mice; Tasaka S et al.; This study tested the hypothesis that very late antigen (VLA)-4 mediates CD18-independent neutrophil emigration into the airspaces induced by either Streptococcus pneumoniae, a stimulus that induces primarily CD18-independent neutrophil emigration, or Escherichia coli, toward which only 20-30% of the total number of neutrophils emigrate through CD18-independent pathways . In wild-type (WT) mice, VLA-4 expression was less on neutrophils that emigrated into the airspaces than on circulating neutrophils . Vascular cell adhesion molecule-1 (VCAM-1) mRNA, the major endothelial cell ligand for VLA-4, increased more in E . coli than in S . pneumoniae pneumonia . VCAM-1 protein expression was not detected in capillaries, the major site of neutrophil emigration . Neutrophil emigration during E . coli or S . pneumoniae pneumonia was similar in mice given antibodies against both CD18 and VLA-4 compared with mice given the anti-CD18 antibody and a control antibody . However, in hematopoietically reconstituted mice with both WT and CD18-deficient neutrophils in their blood, the migration of CD18-deficient neutrophils in response to S . pneumoniae was slightly but significantly less in animals pretreated with the anti-VLA-4 antibody than in those receiving a control antibody . These data suggest that VLA-4 plays a small role in CD18-independent neutrophil emigration, but the majority of CD18-independent neutrophil emigration induced by bacteria in the lungs occurs through VLA-4-independent mechanisms.

Rev Med Chir Soc Med Nat Iasi, 2000 Jul-Sep, 104(3), 37 - 42
{Actual considerations in pneumococcal meningitis}; Rudnic E; Streptococcus pneumoniae has been recognized as a bacterial pathogen in human beings . It was the main cause of meningitis, almost since it was first isolated by Sternberg and Pasteur more than 100 years ago . Meningitis is constantly lethal without specifically treatment . Emergence and diffusion strains of the Streptococcus pneumoniae indicate the changes that are likely in the area of antimicrobial resistance in the last decade . Resistance of Streptococcus pneumoniae to antibiotics has progressed rapidly and is a global problem . This article presents the new information about Streptococcus pneumoniae, and the new possibilities of treatment of the pneumococcal meningitis.

J Infect Dis, 2002 Jul 1, 186(1), 123 - 6 Epub 2002 Jun 14.
Conjugate vaccines against group B Streptococcus types IV and VII; Paoletti LC et al.; Although rarely encountered, group B Streptococcus (GBS) types IV and VII have been isolated from infants and adults with invasive disease . This study was designed to determine the immunogenicity and efficacy in animals of conjugate vaccines prepared with GBS types IV and VII capsular polysaccharide (CPS) . Despite the striking similarities in structure of these 2 carbohydrate antigens, high-titer rabbit antiserum to each conjugate vaccine was serotype specific . Active vaccination of female mice with the conjugate vaccines induced type-specific IgG and resulted in survival of >90% of newborn pups challenged with viable GBS of homologous serotype . If needed, types IV and VII CPS conjugate vaccines of the design described can be added to the formulation of a multivalent GBS vaccine.

J Infect Dis, 2002 Jul 1, 186(1), 118 - 22 Epub 2002 Jun 14.
Emergence of a novel penicillin-nonsusceptible, invasive serotype 35B clone of Streptococcus pneumoniae within the United States; Beall B et al.; Monitoring antibiotic-resistant pneumococcal strains not covered by the 7-valent conjugate vaccine is an important priority . The Centers for Disease Control and Prevention's Active Bacterial Core Surveillance identified 68 invasive penicillin-nonsusceptible serotype 35B (PN35B) isolates recovered from 1995 to 2001 from patients residing in the states of California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New York, Oregon, Tennessee, and Texas . Nonsusceptible isolates accounted for 69% of all serotype 35B isolates recovered during this time . Twelve (18%) of the 68 PN35B isolates recovered since 1995 were obtained from pediatric patients . These 68 isolates exhibited penicillin MICs of 0.25-2 microg/mL and reduced susceptibility to cefotaxime . Representative PN35B isolates exhibited a common chromosomal macrorestriction profile and identical penicillin-binding-protein gene restriction profiles characteristic of penicillin-resistant strains, and they shared a unique 7-locus sequence type that included 3 new alleles . The mosaic pbp2b and divergent ddl sequences were suggestive of interspecies recombination at the ddl-pbp2b chromosomal region.

J Clin Microbiol, 2002 Jul, 40(7), 2642 - 4
NAD-glycohydrolase production and speA and speC distribution in Group A streptococcus (GAS) isolates do not correlate with severe GAS diseases in the Australian population; DelVecchio A et al.; Streptococcus pyogenes isolates from a tropical region and a subtropical region of Australia with high and low incidences of severe streptococcal diseases, respectively, were analyzed for speA, speB, and speC gene distributions and NAD-glycohydrolase expression . No direct correlation of these characteristics with a propensity to cause invasive diseases was observed.

J Clin Microbiol, 2002 Jul, 40(7), 2545 - 54
Molecular peculiarities of the lytA gene isolated from clinical pneumococcal strains that are bile insoluble; Obregon V et al.; The autolytic LytA amidase from 12 bile (deoxycholate)-insoluble streptococcal isolates (formerly classified as atypical Streptococcus pneumoniae) showing different antibiotic resistance patterns was studied . These atypical strains, which autolyze at the end of the stationary phase of growth, contain highly divergent lytA alleles (pairwise evolutionary distances of about 20%) compared to the lytA alleles of typical pneumococci . The atypical LytA amidases exhibit a peculiar deletion of two amino acids responsible for cell wall anchoring in the carboxy-terminal domain and have a reduced specific activity . These enzymes were inhibited by 1% deoxycholate but were activated by 1% Triton X-100, a detergent that could be used as an alternative diagnostic test for this kind of strain . Preparation of functional chimeric enzymes, PCR mutagenesis, and gene replacements demonstrated that the characteristic bile insolubility of these atypical strains was due to their peculiar carboxy-terminal domain and that the 2-amino-acid deletion was responsible for the inhibitory effect of deoxycholate . However, the deletion alone did not affect the specific activity of LytA . A detailed characterization of the genes encoding the 16S rRNA and SodA together with multilocus sequence typing indicated that the strains studied here are not a single clone and, although they cannot be strictly classified as typical pneumococci, they represent a quite diverse pool of organisms closely related to S . pneumoniae . The clinical importance of these findings is underlined by the role of the lytA gene in shaping the course of pneumococcal diseases . This study can also contribute to solving diagnostic problems and to understanding the evolution and pathogenic potential of species of the Streptococcus mitis group.

Appl Environ Microbiol, 2002 Jul, 68(7), 3352 - 7
Molecular characterization and expression of pyruvate formate-lyase-activating enzyme in a ruminal bacterium, Streptococcus bovis; Asanuma N et al.; To clarify the significance of the activation of pyruvate formate-lyase (PFL) by PFL-activating enzyme (PFL-AE) in Streptococcus bovis, the molecular properties and gene expression of PFL-AE were investigated . S . bovis PFL-AE was deduced to consist of 261 amino acids with a molecular mass of 29.9 kDa and appeared to be a monomer protein . Similar to Escherichia coli PFL-AE, S . bovis PFL-AE required Fe(2+) for activity . The gene encoding PFL-AE (act) was found to be polycistronic, and the PFL gene (pfl) was not included . However, the act mRNA level changed in parallel with the pfl mRNA level, responding to growth conditions, and the change was contrary to the change in the lactate dehydrogenase (LDH) mRNA level . PFL-AE synthesis appeared to change in parallel with PFL synthesis . Introduction of a recombinant plasmid containing S . bovis pfl and the pfl promoter into S . bovis did not affect formate and lactate production, which suggests that the activity of the pfl promoter is low . When the pfl promoter was replaced by the S . bovis ldh promoter, PFL was overexpressed, which caused an increase in the formate-to-lactate ratio . However, when PFL-AE was overexpressed, the formate-to-lactate ratio did not change, suggesting that PFL-AE was present at a level that was high enough to activate PFL . When both PFL-AE and PFL were overexpressed, the formate-to-lactate ratio further increased . It is conceivable that LDH activity is much higher than PFL activity, which may explain why the formate-to-lactate ratio is usually low.

Diagn Microbiol Infect Dis, 2002 Jun, 43(2), 163 - 5
Azithromycin treatment failure in community-acquired pneumonia caused by Streptococcus pneumoniae resistant to macrolides by a 23S rRNA mutation; Kays MB et al.; In this report, we describe an azithromycin treatment failure in community-acquired pneumonia . During the first three days of azithromycin, the patient's symptoms worsened, and she was subsequently admitted to the hospital . Blood cultures were positive for a penicillin-susceptible, macrolide-resistant S . pneumoniae . DNA sequencing revealed an A2059G mutation in domain V of the 23S rRNA . To our knowledge, this is the first clinical report of an azithromycin failure in the treatment of S . pneumoniae resistant to macrolides by this mechanism.

Clin Infect Dis, 2002 Jul 15, 35(2), 205 - 8 Epub 2002 Jun 19.
A novel, multiple drug-resistant, serotype 24F strain of Streptococcus pneumoniae that caused meningitis in patients in Naples, Italy; Pantosti A et al.; Three adult patients in Naples, Italy, had meningitis due to multiple drug-resistant serotype 24F Streptococcus pneumoniae isolates . The 3 isolates were genetically indistinguishable and shared pbp2b and pspA sequence types with previously characterized penicillin-resistant clones . This serotype 24F strain was found to be the same clonal type as a previously characterized, penicillin-resistant serotype 14 strain . The novel strain has probably arisen through transformation of a serotype 14 strain with type 24F capsular biosynthetic operon sequences.

Clin Infect Dis, 2002 Jul 15, 35(2), 130 - 9 Epub 2002 Jun 24.
Effect of penicillin resistance of Streptococcus pneumoniae on the presentation, prognosis, and treatment of pneumococcal endocarditis in adults; Martinez E et al.; We performed a clinical study of pneumococcal endocarditis (PE) in adults at 15 major Spanish hospitals during a 21-year period (1978-1998) . During this time, 63 patients had PE due to Streptococcus pneumoniae diagnosed . Of the 63 isolates recovered from these patients, 24 (38%) and 6 (10%) showed resistance to penicillin (minimum inhibitory concentration {MIC}, 0.1-4 microg/mL) and cefotaxime (MIC, 1 microg/mL), respectively . Twenty-two (35%) of the patients died . Left-side heart failure, but not penicillin resistance, was independently associated with a higher risk of death (odds ratio, 1.33; 95% confidence interval, 1.04-1.71; P=.026) . Patients without meningitis who had PE due to penicillin-resistant S . pneumoniae could be treated with high-dose penicillin or a third-generation cephalosporin if the MIC for penicillin was < or =1 microg/mL . For patients with concurrent meningitis, high doses of cefotaxime could be used if the MIC for cefotaxime was < or =1 microg/mL . Early recognition of heart failure and surgery may help to decrease mortality.

Contemp Top Lab Anim Sci, 1999 May, 38(3), 67 - 70
Factors Optimizing the Use of Subcutaneous Vascular Access Ports in Weaned Pigs; Cowart RP et al.; Young, recently weaned pigs were implanted with subcutaneous vascular access ports in experiments designed to determine the relative bioavailability of lead from contaminated soils . In nine experiments, a total of 72 subcutaneous vascular access ports were implanted . Complications were observed in 38.9% of the implanted pigs . Changes in the protocol were implemented in an effort to reduce the rate of complications . The majority of complications were septic processes, including localized infections around the site of the catheter and injection port, hematogenous pulmonary abscessation, endocarditis, and septic arthritis . Staphylococcus aureus, S . hyicus, b-hemolytic Streptococcus species, and Actinomyces pyogenes were cultured from septic processes in these pigs . Our findings suggest that the health of the skin at the time of surgery, the experience of the surgeon, and the immunologic status of the animal influence the risk of septic complications in pigs implanted with subcutaneous vascular access ports.

Clin Microbiol Infect, 2002 Jun, 8(6), 373 - 80
Single- and multistep selection study of the antipneumococcal activity of BMS-284756 compared to ciprofloxacin, levofloxacin, trovafloxacin and moxifloxacin; Clark CL et al.; Single- and Multi-step selection studies were used to test the ability of BMS-284756, ciprofloxacin, levofloxacin, trovafloxacin and moxifloxacin to yield resistant clones from 12 quinolone-susceptible and -resistant Streptococcus pneumoniae strains . Although all quinolones selected, to a greater or lesser degree, for resistant clones with mutations usually in parC or gyrA, BMS-284756 tended to select for resistant clones at a lower rate than other quinolones studied.

Asian Cardiovasc Thorac Ann, 2002 Mar, 10(1), 61 - 3
Superior mesenteric artery aneurysm; Yuksel M et al.; A 38-year old woman with mid-epigastric pain, diarrhea, and weight loss, underwent resection of a superior mesenteric artery aneurysm and primary repair of the artery . Pathological examination showed degenerative atherosclerotic changes, marked medial and intimal thickening, and vegetations . Microbiological studies demonstrated Streptococcus viridans as the infecting organism of this mycotic aneurysm . The patient made a good recovery and remained well after 3 years.

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