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 scrap