J Infect Dis, 2005 Feb 15, 191(4), 596 - 606 Epub 2005 Jan 05. Blockade of the Fas/FasL System Improves Pneumococcal Clearance from the Lungs without Preventing Dissemination of Bacteria to the Spleen; Matute-Bello G et al.; Background . The Fas/FasL system is both proapoptotic and proinflammatory . FasL is inhibited by decoy receptor-3 (DcR3), a naturally occurring decoy receptor . We determined the effects of systemic blockade of the Fas/FasL system by a DcR3 analog (DcR3-a) in mice with pneumococcal pneumonia.Methods . Streptococcus pneumoniae (7.2x105 or 1.9x107 cfu/mL) was instilled intratracheally into untreated C57Bl/6 mice, C57Bl/6 mice treated with DcR3-a, or Fas-deficient lpr mice, and the mice were studied 48 h later.Results . After instillation of the lower bacterial dose, disruption of the Fas/FasL system by either DcR3-a or the lpr mutation resulted in improved clearance of bacteria in the lungs (mean +/- SE, 4.6+/-2.1x106 and 3.5 +/- 1.6 x 10(6) cfu/lung, respectively, vs . 21.9+/-9.3x106 cfu/lung in untreated C57Bl/6 mice; P<.05) and decreased percentage of polymorphonuclear neutrophils in bronchoalveolar lavage fluid (mean +/- SE, 19.3%+/-9.5% and 20.2%+/-7.8%, respectively, vs . 55.0%+/-12.2% in untreated C57Bl/6 mice; P<.05) . These changes were associated with decreased lung concentrations of the proinflammatory cytokines tumor necrosis factor- alpha and macrophage inflammatory protein-2 and with a decrease in apoptotic cells in the alveolar walls.Conclusion . Blockade of the Fas/FasL system by DcR3-a in the lungs improves clearance of bacteria in mice with pneumococcal pneumonia. Clin Infect Dis, 2005 Jan 15, 40(2), 225 - 35 Epub 2004 Dec 21. The molecular epidemiology of Streptococcus pneumoniae with quinolone resistance mutations; Richter SS et al.; BACKGROUND: The purpose of this study was to determine the prevalence of fluoroquinolone resistance and quinolone resistance-determining region (QRDR) mutations among Streptococcus pneumoniae isolates in the United States during the period of 2001-2002 . A second objective was to examine the genetic relatedness of pneumococcal isolates with parC and/or gyrA mutations during the period of 1994-2002 . METHODS: Susceptibility testing was performed for 1902 S . pneumoniae isolates collected in the United States during the period of 2001-2002 . On the basis of the minimum inhibitory concentration (MIC) of ciprofloxacin, 146 isolates were selected from the 2001-2002 study for QRDR analysis of parC, parE, gyrA, and gyrB genes . The genetic relatedness of isolates with parC and/or gyrA mutations from 2001-2002 (n=55) and from 3 US surveillance studies conducted during 1994-2000 (n=56) was determined by pulsed-field gel electrophoresis (PFGE) . RESULTS: Between 1999-2000 and 2001-2002, there was a 2-fold increase in the rate of ciprofloxacin resistance (MIC, >or=4 micro g/mL), from 1.2% to 2.7%, and in the rate of levofloxacin nonsusceptibility (MIC, >or=4 micro g/mL), from 0.6% to 1.3% . The 111 isolates with parC and/or gyrA mutations were assigned to 48 different PFGE types . Forty-four isolates (40%) belonged to 8 PFGE types that were closely related to widespread clones . Fifteen of the 43 levofloxacin-nonsusceptible pneumococci (LNSP) belonged to 4 PFGE types that were closely related to major clones (Spain(23F)-1 {n=6}; Spain(6B)-2 {n=5}, Taiwan(19F)-14 {n=2}, and Tennessee(23F)-4 {n=2}) . CONCLUSION: The population of fluoroquinolone-resistant S . pneumoniae in the United States has increased but remains genetically diverse . However, 35% of LNSP were related to widespread pneumococcal clones, increasing the potential for the rapid spread of quinolone resistance in this species. Clin Microbiol Rev, 2005 Jan, 18(1), 102 - 27 Surface Proteins of Streptococcus agalactiae and Related Proteins in Other Bacterial Pathogens; Lindahl G et al.; Streptococcus agalactiae (group B Streptococcus) is the major cause of invasive bacterial disease, including meningitis, in the neonatal period . Although prophylactic measures have contributed to a substantial reduction in the number of infections, development of a vaccine remains an important goal . While much work in this field has focused on the S . agalactiae polysaccharide capsule, which is an important virulence factor that elicits protective immunity, surface proteins have received increasing attention as potential virulence factors and vaccine components . Here, we summarize current knowledge about S . agalactiae surface proteins, with emphasis on proteins that have been characterized immunochemically and/or elicit protective immunity in animal models . These surface proteins have been implicated in interactions with human epithelial cells, binding to extracellular matrix components, and/or evasion of host immunity . Of note, several S . agalactiae surface proteins are related to surface proteins identified in other bacterial pathogens, emphasizing the general interest of the S . agalactiae proteins . Because some S . agalactiae surface proteins elicit protective immunity, they hold promise as components in a vaccine based only on proteins or as carriers in polysaccharide conjugate vaccines. J Am Osteopath Assoc, 2004 Dec, 104(12), 521 - 6 The newer guidelines for the management of community-acquired pneumonia; Shah PB et al.; Community-acquired pneumonia (CAP) is a leading cause of death in the world and the sixth most common cause of death in the United States . It is the number one cause of death from infectious diseases in the United States . This article reviews the latest available guidelines from two leading organizations-the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) . The IDSA stratifies patients into three categories and recommends antibiotic management based on assigned categories: outpatients, patients admitted to a general medical floor (GMF), and patients requiring intensive care unit (ICU) admission . The ATS, in contrast, stratifies patients into four major groups based on the presence of two cardiopulmonary diseases, certain modifying risk factors that increase the likelihood of acquiring specific infections (such as with drug-resistant Streptococcus pneumoniae, enteric gram-negative organisms, or Pseudomonas aeruginosa), and also based on the site of treatment (such as outpatient setting, GMF, and ICU). J Dairy Sci, 2005 Feb, 88(2), 553 - 9 Interlaboratory proficiency testing as a tool for improving performance in laboratories diagnosing bovine mastitis; Pitkala A et al.; The National Veterinary and Food Research Institute (Finland) and the Veterinary Laboratories Agency of the Quality Assurance Unit, Department for Environment, Food and Rural Affairs, United Kingdom (previously the Ministry of Agriculture, Fisheries and Food) organized a proficiency testing program for laboratories analyzing veterinary mastitis samples . Three test samples with lyophilized strains of common aerobic bacteria were sent to the participating laboratories 7 times between 2000 and 2003 . The participants returned 98% of the requested data . The overall performance of the laboratories varied from 63 to 93% in different testing rounds . All laboratories diagnosed Staphylococcus aureus and Escherichia coli correctly at every round . Improvement in diagnosing individual bacteria was observed for Staphylococcus epidermidis, Streptococcus dysgalactiae, Enterococcus spp . and Klebsiella spp . The overall performance of the laboratories improved with increased participation . The educational role of the program was important . Laboratories working in the veterinary field should implement a documented quality system covering all functions of the laboratory, as well as a planned quality assurance system. Lancet, 2005 Jan 15, 365(9455), 253 - 5 Human polymicrobial infections; Brogden KA et al.; CONTEXT: Polymicrobial diseases, caused by combinations of viruses, bacteria, fungi, and parasites, are being recognised with increasing frequency . In these infections, the presence of one micro-organism generates a niche for other pathogenic micro-organisms to colonise, one micro-organism predisposes the host to colonisation by other micro-organisms, or two or more non-pathogenic micro-organisms together cause disease . STARTING POINT: Recently, Gili Regev-Yochay (JAMA 2004; 292: 716-20) and Debby Bogaert (Lancet 2004; 363: 1871-72), and their colleagues, suggested another interaction: microbial interference-the ability of Streptococcus pneumoniae carriage to protect against Staphylococcus aureus carriage, and the inverse effect of pneumococcal conjugate vaccination on the increased carriage of Staph aureus and Staph-aureus-related disease . Strep pneumoniae carriage protected against Staph aureus carriage, and the bacterial interference could be disrupted by vaccinating children with pneumococcal conjugate vaccines that reduced nasopharyngeal carriage of vaccine-type Strep pneumoniae . WHERE NEXT: The medical community is recognising the significance of polymicrobial diseases and the major types of microbial community interactions associated with human health and disease . Many traditional therapies are just starting to take into account the polymicrobial cause of diseases and the repercussions of treatment and prevention. Microb Drug Resist, 2004 Winter, 10(4), 313 - 20 Occurrence and Characteristics of Erythromycin-Resistant Streptococcus pneumoniae Strains Isolated in Three Major Brazilian States; Mendonca-Souza CR et al.; We investigated the occurrence and phenotypic and genotypic characteristics of erythromycin-resistant Streptococcus pneumoniae strains isolated in three major states in Brazil, from 1990 to 1999 . Of the 931 pneumococcal strains evaluated, 40 (4.3%) were erythromycin-resistant (Ery-R) . Among the 40 Ery-R strains, 90.0%, 80.0%, 27.5%, 5.0%, and 2.5% were resistant to tetracycline, trimethoprim-sulfamethoxazole, penicillin, chloramphenicol, and rifampin, respectively . None of the strains were resistant to ofloxacin or to vancomycin . Most {37 (92.5%)} of the 40 Ery-R isolates presented the MLS(B) phenotype and 3 (7.5%) strains showed the M phenotype . PCR testing indicated that all MLS(B) phenotype isolates harbored the erm(B) gene only, whereas the mef(A/E) gene was present in all isolates presenting the M phenotype . The tet(M) gene was the most frequent (86.1%) among Ery-R isolates that were also resistant to tetracycline . Pulsed-field gel electrophoresis (PFGE) analysis after SmaI digestion revealed the occurrence of clonal relationships within groups of strains belonging to serotypes 14, 19A, and 23F . All Ery-R isolates belonging to serotype 14 were susceptible to penicillin and were included in a single clonal group (named Ery(14)-A) related to the England(14-)9 internationally spread clone. Microb Drug Resist, 2004 Winter, 10(4), 306 - 12 Polyclonal Spread of Erythromycin-Resistant Streptococcus agalactiae in Southern Taiwan; Ko WC et al.; Resistance to erythromycin is common among Streptococcus agalactiae in Taiwan, however the genetic relatedness of erythromycin-resistant isolates has not yet been reported . From 1991 to 2001, 629 clinical isolates of S . agalactiae were collected in a medical center at Tainan in southern Taiwan, of which 189 (30.0%) were resistant to erythromycin . The isolation rate of erythromycin-resistant group B streptococcus (GBS) was stable, irrespective of the clinical sources or study period . Among them, 145 (76.7%) isolates showed the macrolide-lincosamide-streptogramin B (MLS)-resistant phenotype, and 44 (23.3%) had the macrolide (M)- resistant phenotype . Of the isolates with MLS phenotype, 141 (97.2%) isolates harbored the ermB gene alone and only three (2.1%) the ermTR gene, whereas 41 (93.2%) of 44 isolates with M phenotype harbored the mefA/E gene . Of 177 typeable isolates, there were 26 unrelated pulsed-field gel electrophoresis (PFGE) patterns . PFGE type 1 accounted for 17.8% (24/135) of MLS phenotype isolates with the ermB gene and 48.7% (18/37) of M phenotype isolates with the mefA/E gene . During the study period, the proportion of PFGE type 6 decreased significantly, whereas that of type 8 increased . Our results suggest that erythromycin resistance is not uncommon among clinical isolates of S . agalactiae and is, at least, partially related to polyclonal spread in southern Taiwan. J Antimicrob Chemother . 2005 Jan 13; {Epub ahead of print} Evolution of erythromycin resistance in Streptococcus pneumoniae in Italy; Monaco M et al.; OBJECTIVES: To evaluate erythromycin resistance in recent invasive isolates of Streptococcus pneumoniae in Italy, to study the phenotypic and genotypic characteristics of the isolates, and to compare data with those obtained in a previous survey . METHODS: Invasive pneumococcal isolates were obtained from 56 laboratories throughout the country, in 2001-2003 . Isolates were serotyped and antimicrobial susceptibilities determined by Sensititre panels and Etest . A new PCR was performed to detect erythromycin resistance genes . Typing methods for selected erythromycin-resistant isolates included PFGE and multilocus sequence typing (MLST) . RESULTS: One hundred and fifty-five isolates out of 444 (34.9%) were resistant to erythromycin: 95 isolates (21.4%) carried erm(B), 56 (12.6%) carried mef(A) and three carried both genes . One isolate, carrying neither erm(B) nor mef(A), showed a point mutation in domain V of the 23S rRNA genes . The mef(A)-positive isolates carried subtype mef(A) (47 isolates), subtype mef(E) (nine isolates), and both subtype mef(E) and erm(B) (three isolates) . All subtype mef(A) strains, except two, belonged to serotype 14, appeared to be clonally related by PFGE and related to the England(14)-9 clone by MLST . The two isolates belonging to other serotypes showed different genetic backgrounds . CONCLUSIONS: Erythromycin resistance in S . pneumoniae has increased in the last few years in Italy . erm(B) is still the predominant resistance determinant; however, the increase in erythromycin resistance (34.9% versus 28.8% of the previous years) is mainly due to an increase in the proportion of isolates carrying the efflux pump mef(A), whereas the proportion of isolates carrying erm(B) has not changed. Clin Microbiol Infect, 2005 Jan, 11(1), 9 - 14 Activity of the new quinolone WCK 771 against pneumococci; Appelbaum PC et al.; The activity of WCK 771, a new experimental quinolone being developed to overcome quinolone resistance in staphylococci, against quinolone-susceptible and -resistant pneumococci was determined . Comparative activities of ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, clinafloxacin, vancomycin, linezolid, amoxycillin, cefuroxime, azithromycin and clarithromycin were determined with MIC and time-kill experiments . Animal experiments were also performed to test the in-vivo anti-pneumococcal activity of WCK 771 compared to levofloxacin . WCK 771 MIC(50/90) values for 300 quinolone-susceptible Streptococcus pneumoniae isolates (108 penicillin-susceptible, 92 penicillin-intermediate and 100 penicillin-resistant) were 0.5/0.5 mg/L; the MICs of beta-lactams and macrolides rose with those of penicillin G, and all isolates were susceptible to vancomycin and linezolid . WCK 771 MIC(50/90) values for 25 quinolone-resistant pneumococcal isolates were 4/8 mg/L, compared to 0.5/1 mg/L for clinafloxacin, 2/4 mg/L for gatifloxacin and moxifloxacin, 8/16 mg/L for levofloxacin, and 16/>32 mg/L for ciprofloxacin . Time-kill studies showed that WCK 771 was bactericidal against pneumococci after 24 h at 4x MIC, as were the other quinolones tested . Animal model studies showed that WCK 771 had efficacy comparable to that of levofloxacin, by both the oral and subcutaneous routes, for systemic infection caused by three quinolone-susceptible isolates of pneumococci . Overall, WCK 771 was potent both in vivo and in vitro against quinolone-susceptible, but not quinolone-resistant, S . pneumoniae, regardless of penicillin susceptibility. Dis Aquat Organ, 2004 Nov 23, 62(1-2), 177 - 80 Streptococcus iniae type II infections in rainbow trout Oncorhynchus mykiss; Lahav D et al.; Clinical and pathological findings (anorexia, hemorrhage, lethargy, loss of orientation and exophthalmia) indicated that Streptococcus iniae type II is responsible for a fatal disease in rainbow trout . Histopathological findings revealed that S . iniae type II produces a systemic disease, including a diffuse necrotizing myositis . The distribution of viable bacteria in infected tissues substantiated the pathological findings, confirming that S . iniae type II is responsible for a generalized septic disease of rainbow trout. J Biol Chem . 2005 Jan 12; {Epub ahead of print} Conserved interactions in the staphylococcus aureus DNA POLC chromosome replication machine; Bruck I et al.; The PolC holoenzyme replicase of the gram positive Staphylococcus aureus pathogen has been reconstituted from pure subunits . Individual S . aureus replicase subunits are compared to subunits from the gram negative E . coli Pol III holoenzyme for activity and interchangeability . The central organizing subunit, t{tau}, is smaller than its gram negative homolog, yet retains ability to bind ssDNA and contains DNA stimulated ATPase activity comparable to E . coli ttau . S . aureus ttau also stimulates PolC although they do not form as stabile of a complex as E . coli Pol III-ttau . We demonstrate that the extreme C-terminal residues of PolC bind and function with bbeta clamps from different bacteria . Hence, this polymerase-to-clamp interaction is highly conserved . Additionally, the S . aureus ddelta wrench of the clamp loader binds to E . coli bbeta . The S . aureus clamp loader is even capable of loading E . coli bbeta and Streptococcus pyogenes bbeta clamps onto DNA . Interestingly, S . aureus PolC lacks functionality with heterologous bbeta clamps when they are loaded onto DNA by the S . aureus clamp loader, suggesting that the S . aureus clamp loader may have difficulty ejecting from heterologous clamps . Nevertheless, these overall findings underscore the conservation in structure and function of gram positive and gram negative replicases despite over one billion years of evolutionary distance between them. J Biol Chem . 2005 Jan 12; {Epub ahead of print} Differential single-stranded DNA binding properties of the paralogous SsbA and SsbB proteins from streptococcus pneumoniae; Grove DE et al.; The naturally transformable Gram positive bacterium Streptococcus pneumoniae has two single-stranded DNA binding (SSB) proteins, designated SsbA and SsbB . The SsbA protein is similar in size to the well characterized SSB protein from Escherichia coli (SsbEc) . The SsbB protein, in contrast, is a smaller protein that is specifically induced during natural transformation and has no counterpart in E . coli . In this report, the single-stranded DNA (ssDNA) binding properties of the SsbA and SsbB proteins were examined and compared to those of the SsbEc protein . The ssDNA binding properties of the SsbA protein were similar to those of the SsbEc protein in every ssDNA binding assay used in this study . The SsbB protein differed from the SsbA and SsbEc proteins, however, both in its binding to short homopolymeric dTn oligomers (as judged by polyacrylamide gel shift assays), and in its binding to the longer naturally occurring fX and M13 ssDNAs (as judged by agarose gel shift assays and electron microscopic analysis) . The results indicate that an individual SsbB protein binds to ssDNA with an affinity that is similar or higher than that of the SsbA and SsbEc proteins . However, the manner in which multiple SsbB proteins assemble onto a ssDNA molecule differs from that observed with the SsbA and SsbEc proteins . These results represent the first analysis of paralogous SSB proteins from any bacterial species and provide a foundation for further investigations into the biological roles of these proteins. Schweiz Rundsch Med Prax, 2004 Dec 8, 93(50), 2105 - 7 {A patient with confusion and pneumocephalus: what is your diagnosis?}; Cavassini R et al.; We report the case of a 58 year old male who presented with acute meningoencephalitis and pneumocephalus (intracranial air) visualized on head CT scan . Despite the lack of typical clinical signs such as retroauricular tenderness, red tympanic membrane or otorrhea, mastoiditis was suggested by head CT scan . The patient made a full recovery after mastoidectomy and six weeks of antibiotic therapy . Streptococcus pneumoniae grew from a surgical purulent mastoid tissue sample . Mastoiditis and its complications are rare in adults . A high level of clinical suspicion is needed when a patient presents with encephalitis of unclear origin. Gynakol Geburtshilfliche Rundsch, 2005 Jan, 45(1), 19 - 27 {Clinical relevance of antibiotic resistance in obstetrics and gynecology.}; Ruef C; Die Antibiotikaresistenz von Mikroorganismen, die fur Infektionen des Urogenitaltraktes verantwortlich sind, ist ein klinisch relevantes Problem in der Gynakologie und Geburtshilfe . Gleichzeitig wird die Resistenzprufung aufgrund methodologischer Schwierigkeiten sehr selten eingesetzt, so dass genaue Angaben uber die Epidemiologie der Antibiotikaresistenz bei den meisten Erregern fehlen . In verschiedenen Regionen scheint die Antibiotikaresistenz von Trichomonas vaginalis und Gardnerella vaginalis (Metronidazol), Streptococcus agalactiae (Makrolide, Clindamycin), Mycoplasma hominis (Tetracycline, bei vorbestehender intrinsischer Resistenz gegen Makrolide) zuzunehmen . Zusatzlich wurden Einzelfalle klinischer Infektionen durch multiresistente Chlamydia trachomatis berichtet . Das Vorliegen einer Antibiotikaresistenz sollte deshalb bei unbefriedigendem klinischem Verlauf in Betracht gezogen werden . Angesichts der zunehmenden Resistenzproblematik und der zum Teil grossen Wissenslucken sollten die Forschungsanstrengungen auf dem Gebiet der Antibiotikaresistenz bei gynakologischen Infektionen intensiviert werden. Am J Orthod Dentofacial Orthop, 2005 Jan, 127(1), 64 - 6 Preliminary investigation of bacteremia incidence after removal of the Haas palatal expander; Ribeiro Rosa EA et al.; BACKGROUND: The aim of this study was to investigate the presence of bacteria in the bloodstream immediately after removing Haas palatal expanders; this could be considered an invasive procedure . Methods: Eight patients (18.5 +/- 3.9 years old) wearing Haas palatal expanders had 5-mL blood samples taken immediately before and 10 minutes after removal of the apparatus . The blood was aseptically inoculated into hemoculture bottles and incubated at 37 degrees C for 7 days . Medium alterations suggesting bacterial growth were investigated by using Gram staining . Results: Bottles containing blood taken before apparatus removal did not show bacterial growth . However, 4 of the 8 postremoval blood samples showed turbidity after 5 days, and bacterioscopy analysis showed Gram-positive cocci . Subsequent cultures in blood-agar medium plates allowed classifying the bacteria as viridans streptococcus . Conclusions: There is a strong possibility that trauma after removing Haas expanders might be correlated to transitory bacteremia, thereby implying the need for a more careful approach when dealing with special patients, such as those at risk of cardiopathic complications. Am J Orthod Dentofacial Orthop, 2005 Jan, 127(1), 56 - 63 Antibacterial properties of 4 orthodontic cements; Matalon S et al.; BACKGROUND: White spot lesions are observed in nearly 50% of patients undergoing orthodontic treatment . Long-lasting antibacterial properties of orthodontic cements can reduce this phenomenon . Methods: The antibacterial properties of 4 orthodontic cements were evaluated by direct contact test (DCT) and agar diffusion test (ADT) . With the DCT technique, octet specimens of glass ionomer (CX-Plus; Shofu, Kyoto, Japan), reinforced glass ionomer (GC Fuji ORTHO LC; GC Corporation, Tokyo, Japan), and 2 composite (Transbond XT and Transbond Plus; 3M Unitek, Monrovia, Calif) orthodontic cements were placed on the sidewalls of wells of a 96-microtiter plate . Streptococcus mutans cells (ca . 1 x 10 6 ) were placed on the surface of each specimen for 1 hour at 37 degrees C . Then, fresh media was added to each well, and bacterial growth was monitored for 16 hours with a temperature-controlled spectrophotometer . This was repeated on specimens aged in phosphate-buffered saline for 1 day, 1 week, and 1 month . The ADT was performed by placing specimens in wells punched in agar plates . Results: Measurement of the halo in bacterial lawn after 48 hours showed that only the glass ionomer cement (CX-Plus) produced an inhibition zone (1.2 mm around the sample) . Results at the DCT showed that only the reinforced glass ionomer cement (GC Fuji ORTHO LC) exhibited potent antibacterial activity, which lasted 1 week and diminished over the next 3 weeks . Conclusions: The reinforced glass ionomer cement possessed the most potent and long-lasting antibacterial activity. Medicine (Baltimore), 2005 Jan, 84(1), 23 - 34 Hereditary C2 Deficiency in Sweden: Frequent Occurrence of Invasive Infection, Atherosclerosis, and Rheumatic Disease; Jonsson G et al.; ABSTRACT:: Although frequently asymptomatic, homozygous C2 deficiency (C2D) is known to be associated with severe infections and rheumatic disease . We describe the clinical findings in 40 persons with C2D from 33 families identified in Sweden over 25 years . Medical records covering 96% of the accumulated person-years were reviewed, giving a mean observation time of 39 years (range, 1-77 yr) . Severe infection was the predominant clinical manifestation in the cohort: 23 patients had a past history of invasive infections, mainly septicemia or meningitis caused by Streptococcus pneumoniae, and 12 patients had repeated infections of this kind . Nineteen patients had at least 1 episode of pneumonia, and recurrent pneumonia was documented in 10 patients . Repeated infections occurred mainly during infancy and childhood . Systemic lupus erythematosus was found in 10 patients . Another 7 patients had undifferentiated connective tissue disease (n = 4) or vasculitis (n = 3) . We found no correlation between susceptibility to invasive infection and rheumatologic disease . Cardiovascular disease occurred at a high rate, with a total of 10 acute myocardial infarctions and 5 cerebrovascular episodes in 6 patients . Causes of death among the C2D patients were infection (n = 5), acute myocardial infarction (n = 3), and cancer (n = 1) . We suggest that severe infection may be the principal clinical manifestation of C2D . We also provide novel evidence for a possible role of C2D in the development of atherosclerosis consistent with findings in mannan-binding deficiency and experimental C3 deficiency . In addition, we confirm the well-known association between C2D and systemic lupus erythematosus. Clin Diagn Lab Immunol, 2005 Jan, 12(1), 218 - 23 Assignment of Weight-Based Immunoglobulin G1 (IgG1) and IgG2 Units in Antipneumococcal Reference Serum Lot 89-S(F) for Pneumococcal Polysaccharide Serotypes 1, 4, 5, 7F, 9V, and 18C; Sikkema DJ et al.; Weight-based assignments for immunoglobulin G1 (IgG1) and IgG2 subclass antibodies to Streptococcus pneumoniae capsular polysaccharides (PnPs) in antipneumococcal standard reference serum lot 89-S (lot 89-S), also known as lot 89-SF, have been determined for serotypes 1, 4, 5, 7F, 9V, and 18C . This extends the usefulness of lot 89-S beyond the IgG1 and IgG2 subclass assignments for serotypes 3, 6B, 14, 19F, and 23F made previously (A . Soininen, H . Kayhty, I . Seppala, and T . Wuorimaa, Clin . Diagn . Lab . Immunol . 5:561-566, 1998) to cover 11 major serotypes associated with the highest percentage of pneumococcal disease worldwide . A method of equivalence of absorbances in enzyme immunosorbent assays was used to determine the IgG1 and IgG2 antibody concentrations for the additional serotypes in lot 89-S, based on the subclass values previously assigned for PnPs serotypes 6B, 14, and 23F . This cross-standardization method assures consistency with previous antibody assignments in that reference serum . The newly assigned subclass values for serotype 9V, and previously assigned values for serotype 14, were used to quantitate PnPs antibodies in sera from adult and pediatric subjects immunized with a pneumococcal conjugate vaccine . There was a predominance of IgG1 anti-PnPs antibodies in pediatric sera and IgG2 anti-PnPs antibodies in the adult sera . The IgG1 and IgG2 subclass assignments for the 11 PnPs serotypes in antipneumococcal standard reference serum lot 89-S are useful for quantitating and characterizing immune responses to pneumococcal infection and vaccination regimens. J Biol Chem . 2005 Jan 10; {Epub ahead of print} Glutathione synthesis in streptococcus agalactiae: One protein accounts for gamma -glutamylcysteine synthetase and glutathione synthetase activities; Janowiak BE et al.; gamma-Glutamylcysteine synthetase (gamma-GCS) and glutathione synthetase (GS), distinct enzymes that together account for glutathione (GSH) synthesis, have been isolated and characterized from several Gram-negative prokaryotes and from numerous eukaryotes including mammals, amphibians, plants, yeast and protozoa . Glutathione synthesis is relatively uncommon among the Gram-positive bacteria, and, to date, neither the genes nor the proteins involved have been identified . In the present report we show that crude extracts of Streptococcus agalactiae catalyze the gamma-GCS and GS reactions and can synthesize GSH from its constituent amino acids . The putative gene for S . agalactiae gamma-GCS was identified and cloned, and the corresponding protein was expressed and purified . Surprisingly, it was found that the isolated enzyme catalyzes both the ATP-dependent synthesis of L-gamma-glutamyl-L-cysteine from L-glutamate and L-cysteine and the ATP-dependent synthesis of GSH from L-gamma-glutamyl-L-cysteine and glycine . This novel bifunctional enzyme, referred to as gamma-GCS-GS, has been characterized in terms of catalytic activity, substrate specificity, and inhibition by GSH, cystamine and transition-state analog sulfoximines . The N-terminal 518 amino acids of gamma-GCS-GS (total Mr 85 kDa) show 32 % identity and 43 % similarity with E . coli gamma-GCS (Mr 56 kDa), but the C-terminal putative GS domain (remaining 202 amino acids) of gamma-GCS-GS shows no significant homology with known GS sequences . The C-terminus (360 amino acids) is, however, homologous to D-Ala, D-Ala ligase (24 % identity; 38 % similarity), an enzyme having the same protein fold as known GS proteins . These results are discussed in terms of the evolution of GSH synthesis and the possible occurrence of a similar bifunctional GSH synthesis enzyme in other bacterial species. Turk J Pediatr, 2004 Oct-Dec, 46(4), 329 - 32 Distribution of serotypes and antimicrobial resistance of Streptococcus pneumoniae in a children's hospital in Turkey; Ozalp M et al.; Streptococcus pneumoniae isolates resistant to penicillin and other antibiotics have been increasing in many parts of the world . The aim of this study was to evaluate the antimicrobial susceptibilities to penicillin and other commonly used agents in 98 isolates recovered between 1997 and 1998 from clinical specimens from children, and to determine the serotypes/serogroups related to resistance . Susceptibility to penicillin was determined by E-test and disk diffusion tests were used for the other antimicrobials . Serotyping was performed on all the isolates by the quelling reaction . The rates of intermediate- and high-level resistance to penicillin were 29.6% and 2%, respectively . Overall resistance to trimethoprim-sulfamethoxazole was high (46%), of which 21% coexisted with penicillin resistance . Resistance rates to erythromycin and chloramphenicol were 5% and 1%, respectively . Five isolates were multi-drug resistant . The most frequent serotypes associated with penicillin resistance were serotypes 19, 23, 6, 9 and 15. Klin Padiatr, 2005 Jan-Feb, 217(1), 9 - 14 Chlamydophila pneumoniae respiratory tract infection aggravates therapy refractory bronchitis or pneumonia in childhood; Schmidt SM et al.; BACKGROUND: Chlamydophila pneumoniae was frequently found in bronchial secretions of children with therapy-refractory bronchitis or pneumonia . It was studied, how the agent modifies the course of disease and what findings are associated with the infection . PATIENTS AND METHODS: Bronchial secretions obtained at bronchoscopy of 428 children were studied for C . pneumoniae infection using polymerase chain reaction with enzyme immunoassay detection . Children tested negative and positive were compared for their clinical findings . RESULTS: C . pneumoniae was found in 143 children (33 %) . A C . pneumoniae infection has been found to be associated with a purulent bronchial inflammation (90/143 vs . 144/285, p = 0.02), a Streptococcus pneumoniae co-infection (13/143 vs . 6/285, p = 0.002) and a restrictive disturbance (11/51 vs . 8/93, p = 0.04) . Purulent inflammation (Odds ratio 7.9; 95 % confidence interval {CI} 1.6-39.3), 2 co-infections (Odds ratio 14.3; 95 % CI 1.4-144.4) and co-infection with M . pneumoniae (4/4 versus 9/26, p = 0.03; Mantel Haentzel 3.0; 95 % CI 1.1-8.0) were identified as factors more often associated with a restrictive disturbance in children with bronchial C . pneumoniae infection . An adequate antibiotic therapy improved pulmonary function . No association was found for wheezing, eosinophil inflammation of the nasal mucosa, alpha-1 antitrypsin or immunoglobulin deficiency in serum, level of secretory IgA in bronchial mucus, pathological lung scintigram, gastro-esophageal reflux disease, sweat test and other co-infections . CONCLUSIONS: In children with therapy-refractory bronchitis or pneumonia bronchial C . pneumoniae infection was associated with a more severe disease in case of several, mostly bacterial co-infections . Adequate antibiotic therapy for C . pneumoniae infection has been demonstrated to improve pulmonary function. J Clin Neurosci, 2005 Jan, 12(1), 32 - 5 Adult Streptococcus pneumoniae meningitis in Southern Taiwan: epidemiologic trends and prognostic factors; Lee LH et al.; The clinical features of 22 adult patients with Streptococcus pneumoniae meningitis, retrospectively collected over a 16-year period, were reviewed . Otopharyngeal infection, haematogenous spread and cranial neurosurgery continue to be the predominant routes of infection . Most patients acquired the infection in the community, and predisposing underlying conditions are common . The proportion of S . pneumoniae meningitis compared to all microorganisms causing meningitis in adults declined dramatically from 17% in the first 8 study years to 4% in the last 8 study years . However, all penicillin-resistant S . pneumoniae strains were found in the second half of the study period, accounting for 25% of these episodes . The overall mortality rates for the first and second halves of the study period were 43% and 63%, respectively . Third-generation cephalosporins were the antibiotics of choice for the treatment of S . pneumoniae meningitis in this study, however, the emergence of resistant strains may create a therapeutic challenge in the future . To avoid treatment failure, early diagnosis, careful monitoring of the clinical course and the choice of appropriate antibiotics according to the in vitro antimicrobial susceptibilities, are necessary. Proc Natl Acad Sci U S A . 2005 Jan 6; {Epub ahead of print} Active site restructuring regulates ligand recognition in class A penicillin-binding proteins; Macheboeuf P et al.; Bacterial cell division is a complex, multimolecular process that requires biosynthesis of new peptidoglycan by penicillin-binding proteins (PBPs) during cell wall elongation and septum formation steps . Streptococcus pneumoniae has three bifunctional (class A) PBPs that catalyze both polymerization of glycan chains (glycosyltransfer) and cross-linking of pentapeptidic bridges (transpeptidation) during the peptidoglycan biosynthetic process . In addition to playing important roles in cell division, PBPs are also the targets for beta-lactam antibiotics and thus play key roles in drug-resistance mechanisms . The crystal structure of a soluble form of pneumococcal PBP1b (PBP1b*) has been solved to 1.9 A, thus providing previously undescribed structural information regarding a class A PBP from any organism . PBP1b* is a three-domain molecule harboring a short peptide from the glycosyltransferase domain bound to an interdomain linker region, the transpeptidase domain, and a C-terminal region . The structure of PBP1b* complexed with beta-lactam antibiotics reveals that ligand recognition requires a conformational modification involving conserved elements within the cleft . The open and closed structures of PBP1b* suggest how class A PBPs may become activated as novel peptidoglycan synthesis becomes necessary during the cell division process . In addition, this structure provides an initial framework for the understanding of the role of class A PBPs in the development of antibiotic resistance. Contemp Top Lab Anim Sci, 2004 Nov, 43(6), 8 - 13 Assessment of bacterial contamination of drinking water provided to mice; Haist C et al.; The objective of this study was to evaluate whether an 240-ml water bottle provided to individually housed mice would remain potable for a 2-week interval (based on absence of coliforms) . The study used inbred C57BL/6 mice and CB6F1 x C3D2F1 hybrid mice . Test groups were assigned to minimize the variables of strain, caging type (non-ventilated static versus ventilated) and building location . A 3-cc sample of drinking water was removed aseptically from the bottles and vacuum-filtered using a 250-ml filter funnel with a 0.45-mum pore size . The membrane filter was removed using sterile forceps and placed on a blood agar plate for 10 min . The plate was streaked and incubated at 37 degrees C for 5 days . The plates were observed daily, and if growth had occurred, further testing was done to determine specific organisms . Of the 148 samples only 23 had any bacterial growth . Typical bacteria were unspeciated gram-positive bacilli and Staphylococcus, Micrococcus, Streptococcus, and Pantoea species . The absence of coliforms and low percentage of bacterial contamination suggest that drinking water will remain potable for 2 weeks when supplied to an individual mouse. Acta Cardiol, 2004 Dec, 59(6), 658 - 62 Surgical treatment of infective endocarditis; Saleh A et al.; OBJECTIVE: The objective of this study is to determine the surgical indication in the treatment of infective endocarditis . SETTING: Retrospective study in a tertiary care--Wessex Cardiothoracic--Centre . SUBJECTS AND DESIGN: Case records of patients admitted with infective endocarditis for surgical treatment between 1984 to 1994 at Wessex Cardiothoracic Centre were analysed . This analysis includes the age, sex, microbiology results, risk factors, surgical indication and early results . RESULTS: A total of 123 patients was admitted with bacterial endocarditis treated surgically since 1984 . The mean age was 51.9 years with male:female ratio of 3:1 . The most common causative organism was streptococcus (63%) and staphylococcus (30%) . Native valve endocarditis occurred in 111 patients, affecting the aortic, mitral, combined aortic and mitral valve in 69%, 33%, and 8% of cases, respectively . Late prosthetic valve endocarditis occurred in 12 patients . The most common indication for surgery was heart failure (84%), uncontrolled sepsis (8%), and recurrent endocarditis (2.5%) . Hospital mortality was 1.6% . Complete heart block and cerebrovascular accident developed in 4% and 2.4%, respectively . CONCLUSIONS: Heart failure is the main indication for surgery . Valve replacement with mechanical prosthesis is a safe procedure with a low rate of mortality and complication. Epidemiol Infect, 2004 Dec, 132(6), 1073 - 81 The influence of competition and vaccination on the coexistence of two pneumococcal serotypes; Zhang Y et al.; Streptococcus pneumoniae (pneumococcus) is one of the most important bacterial pathogens and a leading cause of mucosal infections (e.g . otitis media) and various forms of serious diseases (e.g . pneumonia, meningitis, bacteraemia) in developing and developed countries . Based on the polysaccharide capsule, there are at least 90 different pneumococcal serotypes, which may compete with each other to colonize the nasopharynx . Newly developed protein-polysaccharide conjugated vaccines have been shown to provide protection against disease caused by the serotypes included in the vaccine, and also against colonization (carriage) . It is feared that yet uncommon, but nonetheless pathogenic serotypes which have been suppressed by competition, may become more prevalent in carriage and disease after large-scale use of conjugate vaccines . In this paper, we use transmission models of pneumococcal carriage to study how competition and vaccination influence the coexistence of two serotypes . According to our results, direct (physical) competition between two pneumococcal serotypes only influences colonization if the duration of naturally acquired immunity is short . By contrast, indirect (antibody-mediated) competition is of influence only if naturally acquired immunity is long lasting . Vaccination reduces the prevalence of the target serotype--an effect that is enforced by the presence of directly competing bacteria . The emergence of a non-target serotype after vaccination is only observed if bacteria compete directly . These results emphasize the importance of studying whether bacteria compete directly or indirectly and for how long people are protected in order to assess the long-term effects of sero-competition. J Clin Microbiol, 2005 Jan, 43(1), 168 - 73 Characterization of ermB gene transposition by Tn1545 and Tn917 in macrolide-resistant Streptococcus pneumoniae isolates; Okitsu N et al.; In Streptococcus pneumoniae, the ermB gene is carried by transposons, such as Tn917 and Tn1545 . This study investigated the relationship between macrolide resistance and the presence of the ermB gene on Tn917 or Tn1545 in 84 Japanese pneumococcal isolates . Macrolide-resistant strains were classified into two groups as follows . Group 1 (19 strains) showed a tendency to high resistance to erythromycin (MIC at which 50% of isolates are inhibited, 4 mg/liter; MIC at which 90% of isolates are inhibited {MIC(90)}, 128 mg/liter) but susceptibility to rokitamycin (MIC(90), 1 mg/liter), with the ermB gene located on Tn1545 . Group 2 (65 strains) showed a tendency to high resistance to both antibiotics (MIC(90)s for both erythromycin and rokitamycin, >128 mg/liter), with the ermB gene located on Tn917 . There were no strains with constitutive macrolide resistance in either group . All of the strains in group 2 had a deletion in the promoter region of ermB and an insertion of the TAAA motif in the leader peptide . The results of pulsed-field gel electrophoresis and serogrouping showed that Tn1545 spread clonally while Tn917 spread both horizontally and clonally . In conclusion, in Japanese macrolide-resistant S . pneumoniae isolates, the ermB gene is carried and spread primarily by Tn917. J Clin Microbiol, 2005 Jan, 43(1), 150 - 5 Comparison of emm typing and ribotyping with three restriction enzymes to characterize clinical isolates of Streptococcus pyogenes; Doktor SZ et al.; A total of 336 Streptococcus pyogenes isolates recently recovered from patients with pharyngitis from 13 countries were characterized by emm typing and riboprinting using an automated Riboprinter (Dupont/Qualicon) based on the patterns produced by three restriction enzymes, EcoRI, PstI, and HindIII . Three enzymes were necessary to increase the discrimination of ribogroups formed by each enzyme . A total of 40 ribogroups and 38 emm sequences (not counting allelic variations) were identified . Multilocus sequence typing was performed on a sampling of the isolates, and those results were consistent with those of both emm typing and ribotyping . Correlations were observed among all three methods. J Clin Microbiol, 2005 Jan, 43(1), 120 - 6 Association between respiratory disease and bacterial and viral infections in British racehorses; Wood JL et al.; Respiratory disease is important in horses, particularly in young Thoroughbred racehorses, and inflammation that is detected in the trachea and bronchi (termed inflammatory airway disease {IAD}) is more significant in this population in terms of impact and frequency than other presentations of respiratory disease . IAD, which is characterized by neutrophilic inflammation, mild clinical signs, and accumulation of mucus in the trachea, may be multifactorial, possibly involving infections and environmental and immunological factors, and its etiology remains unclear . This 3-year longitudinal study of young Thoroughbred racehorses was undertaken to characterize the associations of IAD and nasal discharge with viral and bacterial infections . IAD was statistically associated with tracheal infection with Streptococcus pneumoniae (capsule type 3), Streptococcus zooepidemicus, Actinobacillus spp., and Mycoplasma equirhinis and equine herpesvirus 1 and 4 infections, after adjustment for variation between training yards, seasons, and age groups . The association with S . pneumoniae and S . zooepidemicus was independent of prior viral infection and, critically, was dependent on the numbers of organisms isolated . S . pneumoniae was significant only in horses that were 2 years old or younger . The prevalence and incidence of IAD, S . zooepidemicus, and S . pneumoniae decreased in parallel with age, consistent with increased disease resistance, perhaps by the acquisition of immunity . The study provided evidence for S . zooepidemicus and S . pneumoniae playing an important etiological role in the pathogenesis of IAD in young horses. J Biol Chem . 2005 Jan 5; {Epub ahead of print} Decrypting the biochemical function of an essential gene from streptococcus pneumoniae using thermofluor technology; Carver TE et al.; The protein product of an essential gene of unknown function from Streptococcus pneumoniae was expressed and purified for screening in the ThermoFluor(R) affinity screening assay . This assay can detect ligand binding to proteins in the absence of any information about biological function . The recombinant protein was found to be in a dimeric, native-like folded state and to unfold cooperatively . ThermoFluor was used to screen the protein against a library of 3000 compounds that were specifically selected to provide information about possible biological functions . The results of this screen identified pyridoxal phosphate and pyridoxamine phosphate as equilibrium binding ligands (Kd ~ 50 pM, Kd ~ 2.5 uM, respectively), consistent with an enzymatic function in which pyridoxal phosphate is serves as a cofactor . Several nucleotides and nucleotide sugars were also identified as ligands of this protein . Sequence comparison with two enzymes of known structure but relatively low overall sequence homology established that several key residues directly involved in pyridoxal phosphate binding were strictly conserved . Screening a collection of generic drugs and natural products identified the anti-fungal compound Canescin A as an irreversible covalent modifier of the enzyme . Our investigation of this protein indicates that its probable biological role is that of a nucleoside diphospho-keto-sugar aminotransferase, although the preferred keto-sugar substrate remains unknown . These experiments demonstrate the utility of a generic affinity-based ligand binding technology in decrypting possible biological functions of a protein, an approach that is both independent of and complementary to existing genomic and proteomic technologies. Epidemiol Mikrobiol Imunol, 2004 Nov, 53(4), 196 - 202 {Resistance to macrolides in the species Streptococcus pyogenes in the Czech Republic in 1996-2003}; Urbaskova P et al.; The study of the prevalence of erythromycin resistance in 22 169 S . pyogenes strains in the Czech Republic in 1996-2003 on the background of rough data on the nationwide consumption of macrolide antibiotics confirmed that the exponential growth of resistance observed in 1998-2001 copied with a delay the rise in macrolide antibiotic consumption recorded in 1992-1995 . The highest frequency of erythromycin resistance was found in 2001 (16.5%) with a subsequent decrease to 14.5% in 2002 and to 9.1% in 2003 . The drop in resistance followed the stagnation in macrolide consumption and its decrease by 17% in 2002 . Upward and downward trends in macrolide resistance in different regions and age groups copied the nationwide trends with some quantitative differences that could not be analyzed in view of the lack of detailed data on antibiotic consumption . A 99.5% concordance was found between the results of the phenotypic method and those of detection of genes coding for constitutive, inducible and efflux resistance to macrolide-lincosamide-streptograminB (MLSB) antibiotics . In 2001 when the highest erythromycin resistance was recorded in the Czech Republic, most of the tested strains (91.2%) showed resistance to all MLSB antibiotics, with macrolide efflux (susceptibility to lincosamides and 16-membered macrolides was conserved) being implicated in resistance of 8.8% of the strains only . In 2003, the number of erythromycin resistant strains decreased and the resistance mechanism was ascribed to macrolide efflux in 26.8% of them . Almost all of the strains with constitutive or induced MLSB resistance are also resistant to either tetracycline or bacitracin or both . In the light of S . pyogenes resistance to bacitracin, the bacitracin disk is not usable in preliminary identification any more. Microbiology, 2005 Jan, 151(Pt 1), 157 - 66 A unique nine-gene comY operon in Streptococcus mutans; Merritt J et al.; Many Gram-positive and Gram-negative bacteria possess natural competence mechanisms for DNA capture and internalization . In Bacillus subtilis, natural competence is absolutely dependent upon the presence of a seven-gene operon known as the comG operon (comGA-G) . In species of Streptococcus, this function has been described for a four-gene operon (comYA-D in Streptococcus gordonii and cglA-D in Streptococcus pneumoniae) . In this study, a nine-orf operon (named comYA-I) required for natural competence in Streptococcus mutans was identified and characterized . Orf analysis of this operon indicates that the first four Orfs (ComYA-D) share strong homology with ComYA-D of S . gordonii and CglA-D of S . pneumoniae, the fifth to seventh Orfs (ComYE-G) match conserved hypothetical proteins from various species of Streptococcus with ComYF possessing a predicted ComGF domain, the eighth Orf (ComYH) shows a strong homology to numerous DNA methyltransferases from restriction/modification systems, and the ninth Orf (ComYI) is homologous to acetate kinase (AckA) . RT-PCR analysis of the orf junctions confirmed that all nine orfs were present in a single transcript, while real-time RT-PCR analysis demonstrated that these orfs were expressed at a level very similar to that of the first orf in the operon . Mutations were constructed in all nine putative orfs . The first seven genes (comYA-G) were found to be essential for natural competence, while comYH and comYI had reduced and normal natural competence ability, respectively . Analyses of S . mutans comY-luciferase reporter fusions indicated that comY expression is growth-phase dependent, with maximal expression at an OD(600) of about 0.2, while mutations in ciaH, comC and luxS reduced the level of comY expression . In addition, comY operon expression appears to be correlated with natural competence ability. Clin Nephrol, 2004 Dec, 62(6), 461 - 4 An unusual endocarditis-induced crescentic glomerulonephritis treated by plasmapheresis; Couzi L et al.; A 58-year-old man presented with fever and a rapidly progressive glomerulonephritis . An infective endocarditis due to Streptococcus parasanguis was diagnosed . A renal biopsy revealed type III pauci-immune crescentic glomerulonephritis . As first-line therapy, antibiotics were administered alone . Faced to the unsuccessful anti-infective approach, corticosteroid therapy was added as a second-line therapy . Finally, plasmapheresis introduced as the third-line therapy, significantly improved renal function . This case is an original type III rapidly progressive glomerulonephritis, since ANCA were repeatedly found negative . In very few cases, plasmapheresis was successfully used for the treatment of infective endocarditis-induced crescentic glomerulonephritis . The pathophysiology and the potential efficiency of plasmapheresis are discussed. Pediatrics, 2005 Jan, 115(1), e112 - 4 Group A streptococcal subdural empyema as a complication of varicella; Ulloa-Gutierrez R et al.; Group A beta-hemolytic streptococcus and Staphylococcus aureus are the 2 most common pathogens implicated in secondary invasive bacterial disease after varicella . We describe a 3-month-old male infant from British Columbia, Canada, who presented on day 5 of varicella skin rash with fever, seizures, lethargy, and evidence of intracranial hypertension . A prominent subdural empyema was documented, and Streptococcus pyogenes was recovered from the subdural fluid . Central nervous system bacterial complications should be part of the differential diagnosis for infants and children with chickenpox who present with fever, lethargy, focal seizures, or similar neurologic findings . This case illustrates the importance of universal varicella vaccination to prevent associated bacterial complications of chickenpox. J Bacteriol, 2005 Jan, 187(2), 795 - 9 Cloning, Purification, and Enzymatic Properties of Dipeptidyl Peptidase IV from the Swine Pathogen Streptococcus suis; Jobin MC et al.; In this study, the dipeptidyl peptidase IV (DPP IV) of the swine pathogen Streptococcus suis was cloned, overexpressed in Escherichia coli, and characterized . The coding region comprises 2,268 nucleotides containing an open reading frame that codes for a 755-amino-acid protein with a calculated molecular mass of 85 kDa . The amino acid sequence contained the sequence Gly-X-Ser-X-X-Gly, which is a consensus motif flanking the active-site serine shared by serine proteases . The recombinant DPP IV showed a high affinity for the synthetic peptide glycine-proline-p-nitroanilide and was strongly inhibited by Hg(2+) and diprotin A. Diagn Microbiol Infect Dis, 2005 Jan, 51(1), 45 - 9 Assessment of pharmacokinetic-pharmacodynamic target attainment of gemifloxacin against Streptococcus pneumoniae; Owens RC Jr et al.; The treatment of community-acquired respiratory tract infections has been complicated by the emergence of multidrug-resistant Streptococcus pneumoniae . Although traditionally rare, a growing concern for fluoroquinolone-resistant pneumococci has surfaced . More pharmacodynamically potent antimicrobial agents are clearly needed, as the use of such agents may further optimize clinical and microbiological outcomes for patients and slow the emergence of fluoroquinolone resistance . For fluoroquinolones, the ratio of the 24-h area under the concentration-time curve of the agent to the minimum inhibitory concentration of the agent against the pathogen for the fraction of unbound drug is the major pharmacokinetic-pharmacodynamic (PK-PD) measure correlating with efficacy in nonclinical models and infected patients . A 2500-patient Monte Carlo simulation, utilizing a patient-population pharmacokinetic model derived from phase 3 registration trials and the minimum inhibitory concentration distribution for gemifloxacin against 3117 clinical strains of S . pneumoniae, was carried out to estimate the probability of gemifloxacin attaining exposures associated with efficacy . The overall probability PK-PD target attainment for gemifloxacin was greater than 0.99 . Gemifloxacin is among the most pharmacodynamically potent fluoroquinolones and is more potent than ciprofloxacin, ofloxacin, and levofloxacin . Preferential use of pharmacodynamically potent agents over other alternatives may lead to improved clinical outcomes and decreased selection of fluoroquinolone-resistant pneumococci. Diagn Microbiol Infect Dis, 2005 Jan, 51(1), 31 - 37 Relationship between increased levofloxacin use and decreased susceptibility of Streptococcus pneumoniae in the United States; Bhavnani SM et al.; Increasing reports of fluoroquinolone-non-susceptible Streptococcus pneumoniae are of clinical concern . We examined the relationship between outpatient fluoroquinolone use and susceptibility of community-acquired S . pneumoniae isolates . Using multivariable general linear modeling, US SENTRY Antimicrobial Surveillance Program and Intercontinental Medical Statistics data (1997-2002) were analyzed to determine the influence of selected patient-, institution-, and geographic region-specific factors, including local fluoroquinolone usage, on the minimum inhibitory concentration (MIC) of levofloxacin against S . pneumoniae . Levofloxacin MIC(50), MIC(90), and MIC range (n = 384 from 26 hospitals) were 1, 1, and </=0.5 to >4 mug/mL, respectively . Variables associated with changes in geometric mean MIC included geographical region (P < 0.0001), medical service (P = 0.0002), study year (P = 0.0006), primary diagnosis group (P = 0.02), and 2 interactions (duration of hospital stay before isolate collection by bed capacity, P = 0.06, and levofloxacin use by geographical region, P = 0.08; P < 0.001 when study year was removed from the model) . MIC increased with levofloxacin use across all geographical regions, with increases of 54% and 126% in the southwest and west, respectively . In contrast to other fluoroquinolones, increased levofloxacin use, along with other variables, was associated with decreased pneumococcal susceptibility . Given the US environment of increasing pneumococcal resistance, these data may be useful in better understanding factors related to emergence of fluoroquinolone resistance. Medicina (B Aires), 2004, 64(2), 143 - 5 Erythromycin-resistant Streptococcus pyogenes in Argentina; Lopardo HA et al.; Erythromycin (ERY) resistance in Streptococcus pyogenes has recently emerged as a problem of growing concern all through the world . We are presenting the comparison of results of the continuous surveillance of erythromycin resistance in S . pyogenes performed since 1989 in the Hospital de Pediatria J.P.Garrahan of Buenos Aires City, with independently observed rates in other five centers of Buenos Aires and seven centers of six other Argentinian cities, obtained between 1999 and 2001 . A significant increase of erythromycin resistance was observed among S . pyogenes isolated in the Hospital Garrahan (6.6% in 1998-1999 to 9.9% in 2000) . Similar trends were also detected in other centers of other Argentinian cities when recent data were compared to results of a multicenter study performed in 1995 . However, lower rates of resistance were recorded in Mendoza, Cipolletti and Neuquen in comparison with data of 1995, 1998 and 1998 respectively . The reason of such decreasing resistance rates deserves to be investigated . The average of ERY-resistance rates obtained in the surveyed centers was 6.7% (range 0.5-14.1%) . Control of antimicrobial use should be performed to warrant the future effectiveness of macrolide antibiotics regarding the positive association between use and resistance . These results also suggest that susceptibility tests for macrolides should be performed whenever S . pyogenes is isolated in Argentina. Vet Microbiol, 2005 Jan 31, 105(2), 143 - 7 Epub 2004 Dec 19. Antimicrobial susceptibility of clinical strains of Streptococcus suis isolated from pigs in Spain; Vela AI et al.; The antimicrobial susceptibility of 151 clinical Streptococcus suis strains isolated from diseased pigs in Spain was determined by a microdilution method . Isolates were mostly susceptible to beta-lactam antimicrobials, aminoglycosides, enrofloxacin, novobiocin and spectinomycin . More than 87% of the S . suis isolates were resistant to tetracyclines, sulphonamides, macrolides and clindamycin . Strains of serotype 9 were significantly more resistant than strains of serotype 2 (P<0.05) to tylosin (94% versus 77%) and clindamycin (94% versus 64%) . Eighty-seven percent of the S . suis isolates were resistant to at least four antimicrobials and nine isolates (6%) were resistant to at least six antimicrobials . The most frequently identified multidrug pattern involved resistance against tetracyclines, sulphonamides, macrolides and lincosamides, with 69% of the isolates exhibiting this resistotype . Fifteen out of the 22 strains of serotype 2 (68.2%), and 84 out of the 98 of the strains of serotype 9 (85.7%) exhibited this resistotype, indicating its widespread distribution among the strains of the two most frequently isolated serotypes. Int J Pediatr Otorhinolaryngol, 2005 Jan, 69(1), 65 - 8 Treatment of non-streptococcal tonsillitis with metronidazole; Brook I et al.; The potential role of anaerobic bacteria in acute tonsillitis was investigated in a retrospective study that evaluated the efficacy of antimicrobial therapy with metronidazole on the management of acute episodes of non-beta-hemolytic streptococcal tonsillitis (NST) . Forty children suffering from NST were included, 20 that were treated with metronidazole 250mg b.i.d . for 10 day, and 20 that had received no therapy . The efficacy of therapy was evaluated by the ability to alleviate the symptoms of acute infection . As compared with the untreated group, the group that received metronidazole, had a significant reduction in fever and sore throat one day after initiation of therapy, a significant reduction in the presence of fever, pharyngeal injection and sore throat within 2 days, and reduction in pharyngeal injection and tonsillar size at day 3 . These findings illustrated that metronidazole therapy was more efficacious than no therapy in relieving the signs and symptoms of acute episodes of NST . These findings should encourage further studies that are prospective and blinded that are needed to evaluate the use of antimicrobials effective against anaerobic bacteria in the treatment of non-GABHS (group A-beta-hemolytic streptococcus) tonsillitis. Obstet Gynecol, 2005 Jan, 105(1), 18 - 23 Acute pyelonephritis in pregnancy; Hill JB et al.; OBJECTIVE: To examine the incidence of pyelonephritis and the incidence of risk factors, microbial pathogens, and obstetric complications in women with acute antepartum pyelonephritis . METHODS: For 2 years, information on pregnant women with acute pyelonephritis was collected in a longitudinal study . All women were admitted to the hospital and treated with intravenous antimicrobial agents . We compared the pregnancy outcomes of these women with those of the general obstetric population received at our hospital during the same time period . RESULTS: Four hundred forty cases of acute antepartum pyelonephritis were identified during the study period (incidence 1.4%) . Although there were no significant differences in ethnicity, pyelonephritis was associated with nulliparity (44% versus 37%, P = .003) and young age (P = .003) . Thirteen percent of the women had a known risk factor for pyelonephritis . Acute pyelonephritis occurred more often in the second trimester (53%), and the predominant uropathogens were Escherichia coli (70%) and gram-positive organisms, including group B beta Streptococcus (10%) . Complications included anemia (23%), septicemia (17%), transient renal dysfunction (2%), and pulmonary insufficiency (7%) . CONCLUSION: The incidence of pyelonephritis has remained low in the era of routine prenatal screening for asymptomatic bacteriuria . First-trimester pyelonephritis accounts for over 1 in 5 antepartum cases . Gram-positive uropathogens are found more commonly as pregnancy progresses . Maternal complications continue, but poor obstetrical outcomes are rare . LEVEL OF EVIDENCE: II-3. J Biol Chem . 2004 Dec 28; {Epub ahead of print} Biosynthesis of hyaluronan: Direction of chain elongation; Bodevin-Authelet S et al.; Hyaluronan (HA), a functionally essential glycosaminoglycan in vertebrate tissues and a putative virulence factor in certain pathogenic bacteria, is an extended linear polymer composed of alternating units of glucuronic acid (GlcA) and N-acetylglucosamine (GlcNAc) . Uncertainty regarding the mechanism of HA biosynthesis has included the directionality of chain elongation, i.e . whether addition of monosaccharide units occurs at the reducing or non-reducing terminus of nascent chains . We have investigated this problem using yeast-derived recombinant HA synthases from Xenopus laevis (xlHAS1) and from Streptococcus pyogenes (spHAS) . The enzymes were incubated with UDP-{3H}GlcA and UDP-{14C}GlcNAc, under experimental conditions designed to yield HA chains with differentially labeled reducing-terminal and non-reducing terminal domains . Digestion of the products with a mixture of b-glucuronidase and b-N-acetylglucosaminidase exoenzymes resulted in truncation of the HA chain strictly from the non-reducing end, and release of labeled monosaccharides . The change in 3H/14C ratio of the monosaccharide fraction, during the course of exoglycosidase digestion, was interpreted to indicate whether sugar units had been added at the reducing or non-reducing end . The results demonstrate that the vertebrate xlHAS1 and the bacterial spHAS extend HA in opposite directions . Chain elongation catalyzed by xlHAS1 occurs at the non-reducing end of the HA chain, whereas elongation catalyzed by spHAS occurs at the reducing end . The spHAS is the first glycosyltransferase that has been unanimously demonstrated to function at the reducing end of a growing glycosaminoglycan chain. Anal Biochem, 2005 Jan 15, 336(2), 262 - 72 Characterization and quantification of C-polysaccharide in Streptococcus pneumoniae capsular polysaccharide preparations; Xu Q et al.; Purified capsular polysaccharide preparations from Streptococcus pneumoniae that are used for vaccine production typically contain residual levels of C-polysaccharide (C-Ps) . Residual C-Ps is typically found in one of two forms, either chemically linked to the capsular polysaccharide (bound) or present by itself (free) . Two analytical methods have been developed and applied to determine the relative percentages of the two C-Ps forms present in various capsular polysaccharide preparations . Both methods differentiate the two forms of C-Ps according to the difference of their hydrodynamic sizes . One method is based on labeling C-Ps with a fluorescent tag and separating the two forms of C-Ps by high-performance size exclusion chromatography with on-line refractive index and fluorescence detection, and the other method is based on measuring self-diffusion rates of the two forms of C-Ps by nuclear magnetic resonance (NMR) and quantifying each form with deconvolution . Both methods were evaluated for relative accuracy, precision, and ease of application, and they were found to provide comparable results for a large number of pneumococcal polysaccharide preparations . These analyses, combined with other quantitative NMR measurement of total C-Ps in the polysaccharide powder, provide a more refined means of evaluating the amount of each form of C-Ps in polysaccharide preparations targeted for vaccine production. Carbohydr Res, 2005 Jan 17, 340(1), 91 - 96 The teichoic acid (C-polysaccharide) synthesized by Streptococcus pneumoniae serotype 5 has a specific structure; Vialle S et al.; The teichoic acid synthesized by Streptococcus pneumoniae serotype 5, also known as pneumococcal common antigen (C-polysaccharide), was purified . On the basis of compositional analysis, HPAEC-PAD analysis, MALDI-TOF mass spectrometry and NMR spectroscopy, made on the native polysaccharide and on the dephosphorylated repeating unit, the following structure is proposed: This C-polysaccharide (C-PS), differs from those previously described by the replacement of Glc by Gal in its repeating unit structure. Carbohydr Res, 2005 Jan 17, 340(1), 7 - 13 Synthesis of oligosaccharides related to the repeating unit of the capsular polysaccharide from Streptococcus pneumoniae type 37; Larsson EA et al.; A tetra- and a pentasaccharide were synthesized as analogues to the structure of the Streptococcus pneumoniae type 37 capsular polysaccharide, a homopolymer with a disaccharide-repeating unit of -->3){beta-d-Glcp-(1-->2)}-beta-d-Glcp-(1--> . Synthesis of the tetrasaccharide employed a beta-(1-->2)-diglycosylation of a beta-(1-->3)-linked disaccharide . Subsequently, the pentasaccharide was synthesized from a suitably protected tetrasaccharide derivative by a beta-(1-->3)-extension at O-3' . Steric crowding was found to be an important factor in the formation of the pentasaccharide. Med Mal Infect, 2004 Feb, 34(2), 83 - 5 {Evolution of Streptococcus pneumoniae antibiotic resistance in Abidjan: update on nasopharyngeal carriage, from 1997 to 2001}; Kacou-N'douba A et al.; The emerging antibiotic resistance and worldwide diffusion of Streptococcus pneumoniae strains is an important public health problem . OBJECTIVES: The aims of this study were to study the evolution of S . pneumoniae resistance rates to penicillin G and other antimicrobials from nasopharyngeal carriage . METHOD: Four hundred and eighty-two nasopharyngeal samples of S . pneumoniae were studied from 1997 to 2001 . The Kirby-Bauer technique was used to screen the susceptibility of samples and completed with the determination of penicillin G minimal inhibitory concentration using the E-test . RESULTS: Resistance to penicillin increased from 1997 to 2001: 8.5% in 1997, 20.7% in 1998, 16% in 1999, and 23.5% in 2001 . However, the resistance to other beta-lactam antibiotics was low . The rate of resistance to cotrimoxazole increased from 52.2% in 1997 to 84.3% in 2001, with a higher degree of resistance in 2001 . The resistance of S . pneumoniae to tetracycline increased . In contrast, the prevalence of erythromycin-resistant pneumococcal samples decreased from 11.6% in 1997 to 8% in 2001 . The resistance to three or more antibiotics (multi-drug resistant) was also increased from 9.4% in 1997 to 23.5% in 2001 . CONCLUSION: This data shows that carriage of antibiotic-resistant pneumococci is increasing in Abidjan . It will be interesting to assess the current bacterial resistance patterns by a national epidemiological observatory. Clin Exp Nephrol, 2004 Dec, 8(4), 356 - 8 Acute glomerulonephritis in three siblings and suspected emm49-type Streptococcus pyogenes infection; Motoyama O et al.; Three siblings with poststreptococcal acute glomerulonephritis are presented . Streptococcal infection, impetigo, and pharyngitis preceded the acute glomerulonephritis . In one patient, emm49-type Streptococcus pyogenes was isolated, a strain which has not been reported as nephritogenic in Japan. J Hepatobiliary Pancreat Surg, 2004, 11(6), 426 - 9 Successful treatment of ruptured hepatocellular carcinoma with intraperitoneal injection of OK-432; Shiratori M et al.; We report a 51-year-old man with a ruptured hepatocellular carcinoma (HCC) . He was admitted to the hospital with abdominal pain and distension . Imaging studies revealed massive ascites, liver cirrhosis, and a 3-cm tumor at the inferior edge of the medial segment of the liver, with adhesions to the greater omentum . Abdominal paracentesis showed bloody ascites, and the patient was diagnosed with a ruptured HCC . OK-432, an immunomodulatory agent prepared from an attenuated strain of Streptococcus pyogenes, was injected (10 KE) into the peritoneal cavity four times within 1 week; the massive ascites disappeared, and the serum alpha-fetoprotein (AFP) level decreased to within the normal limits . Afterwards, he underwent a curative operation for HCC . His postoperative course was uneventful and he was discharged from the hospital on the twenty-second postoperative day . He had shown no evidence of recurrence or metastases at the time he died of hepatic failure related to alcohol abuse 9 months after the operation. Infect Immun, 2005 Jan, 73(1), 431 - 5 Invasiveness of serotypes and clones of Streptococcus pneumoniae among children in Finland; Hanage WP et al.; Streptococcus pneumoniae (the pneumococcus) causes diseases from otitis media to life-threatening invasive infection . The species is extremely antigenically and clonally diverse . We wished to determine odds ratios (ORs) for serotypes and clones of S . pneumoniae that cause invasive disease in Finland . A total of 224 isolates of S . pneumoniae from cases of invasive disease in children <2 years of age in Finland between 1995 and 1999 were serotyped, and sequence types (STs) were determined by multilocus sequence typing . These STs were compared with a previously published carriage data set . STs from invasive disease were significantly less diverse than those from carriage (invasive disease, 0.038 +/- 0.01; carriage, 0.019 +/- 0.005) . The ORs of serotypes 14, 18C, 19A, and 6B were significantly greater than 1, indicating association with invasive disease . The ORs of 6A and 11A were significantly less than 1 . The difference between 6A and 6B is significant, which suggests that relatively subtle changes in the capsule may have a dramatic effect upon disease potential . We found that ST 156, the Spain(9V)-3 clone which mainly expressed serotype 14 in Finland, is strongly associated with invasive disease (OR, 10.1; 95% confidence interval, 1.3 to 79.5) . Significant associations with invasive disease were also detected for STs 482, 191, 124, and 138, and associations with carriage were detected for STs 485 and 62 . These results demonstrate the invasive phenotype of the serotype 14 variant of the Spain(9V)-3 clone and differences between members of the same serogroup in invasive disease potential. Infect Immun, 2005 Jan, 73(1), 325 - 33 A peptide mimotope of type 8 pneumococcal capsular polysaccharide induces a protective immune response in mice; Buchwald UK et al.; Increasing antibiotic resistance and a rising patient population at risk for infection due to impaired immunity underscore the importance of vaccination against pneumococci . However, available capsular polysaccharide vaccines are often poorly immunogenic in patients at risk for pneumococcal disease . The goal of this study was to explore the potential of peptide mimotopes to function as alternative vaccine antigens to elicit a type-specific antibody response to pneumococci . We used a human monoclonal immunoglobulin A (IgA) antibody (NAD) to type 8 Streptococcus pneumoniae capsular polysaccharide (type 8 PS) to screen a phage display library, and the phage PUB1 displaying the peptide FHLPYNHNWFAL was selected after three rounds of biopanning . Inhibition studies with phage-displayed peptide or the peptide PUB1 and type 8 PS showed that PUB1 is a mimetic of type 8 PS . PUB1 conjugated to tetanus toxoid (PUB1-TT) induced a type 8 PS-specific antibody response in BALB/c mice, further defining it as a mimotope of type 8 PS . The administration of immune sera obtained from PUB1-TT-immunized mice earlier (days 14 and 21) and later (days 87 and 100) after primary and reimmunization resulted in a highly significant prolongation of the survival of naive mice after pneumococcal challenge compared to controls . The survival of PUB1-TT-immunized mice was also prolonged after pneumococcal challenge nearly 4 months after primary immunization . The efficacy of PUB1-TT-induced immune sera provides proof of principle that a mimotope-induced antibody response can protect against pneumococci and suggests that peptide mimotopes selected by type-specific human antibodies could hold promise as immunogens for pneumococci. Infect Immun, 2005 Jan, 73(1), 298 - 307 Both innate immunity and type 1 humoral immunity to Streptococcus pneumoniae are mediated by MyD88 but differ in their relative levels of dependence on toll-like receptor 2; Khan AQ et al.; Little is known regarding the role of Toll-like receptors (TLRs) in regulating protein- and polysaccharide-specific immunoglobulin (Ig) isotype production in response to an in vivo challenge with an extracellular bacterium . In this report we demonstrate that MyD88(-/-), but not TLR2(-/-), mice are markedly defective in their induction of multiple splenic proinflammatory cytokine- and chemokine-specific mRNAs after intraperitoneal (i.p.) challenge with heat-killed Streptococcus pneumoniae capsular type 14 (S . pneumoniae type 14) . This is correlated with analogous responses in splenic cytokine protein release in vitro following addition of S . pneumoniae type 14 . Consistent with these data, naive MyD88(-/-), but not TLR2(-/-), mice are more sensitive to killing following i.p . challenge with live S . pneumoniae type 14, relative to responses in wild-type mice . However, prior immunization of MyD88(-/-) mice with heat-killed S . pneumoniae type 14 protects against an otherwise-lethal challenge with live S . pneumoniae type 14 . Surprisingly, both MyD88(-/-) and TLR2(-/-) mice exhibit striking and equivalent defects in elicitation of type 1 IgG isotypes (IgG3, IgG2b, and IgG2a), but not the type 2 IgG isotype, IgG1, specific for several protein and polysaccharide antigens, in response to i.p . challenge with heat-killed S . pneumoniae type 14 . Of note, the type 1 IgG isotype titers specific for pneumococcal surface protein A are reduced in MyD88(-/-) mice but not TLR2(-/-) mice . These data suggest that distinct TLRs may differentially regulate innate versus adaptive humoral immunity to intact S . pneumoniae and are the first to implicate a role for TLR2 in shaping an in vivo type 1 IgG humoral immune response to a gram-positive extracellular bacterium. EMBO J . 2004 Dec 16; {Epub ahead of print} Solution structure of choline binding protein A, the major adhesin of Streptococcus pneumoniae; Luo R et al.; Streptococcus pneumoniae (pneumococcus) remains a significant health threat worldwide, especially to the young and old . While some of the biomolecules involved in pneumococcal pathogenesis are known and understood in mechanistic terms, little is known about the molecular details of bacterium/host interactions . We report here the solution structure of the 'repeated' adhesion domains (domains R1 and R2) of the principal pneumococcal adhesin, choline binding protein A (CbpA) . Further, we provide insights into the mechanism by which CbpA binds its human receptor, polymeric immunoglobulin receptor (pIgR) . The R domains, comprised of 12 imperfect copies of the leucine zipper heptad motif, adopt a unique 3-alpha-helix, raft-like structure . Each pair of alpha-helices is antiparallel and conserved residues in the loop between Helices 1 and 2 exhibit a novel 'tyrosine fork' structure that is involved in binding pIgR . This and other structural features that we show are conserved in most pneumococcal strains appear to generally play an important role in bacterial adhesion to pIgR . Interestingly, pneumococcus is the only bacterium known to adhere to and invade human cells by binding to pIgR. Antimicrob Agents Chemother, 2005 Jan, 49(1), 464 - 6 Influence of carbon dioxide on the MIC of telithromycin for Streptococcus pneumoniae: an in vitro-in vivo study; Batard E et al.; Incubation in CO(2) resulted in higher (> or =3 doubling dilution) MICs of telithromycin than those found in ambient air for 31.2% of 346 Streptococcus pneumoniae ermB-positive strains . An increased telithromycin MIC in CO(2) was not correlated with loss of its activity in the murine sepsis/peritonitis model. Antimicrob Agents Chemother, 2005 Jan, 49(1), 418 - 20 Streptococcus pyogenes pharyngeal isolates with reduced susceptibility to ciprofloxacin in spain: mechanisms of resistance and clonal diversity; Alberti S et al.; A survey of emm gene sequences and an analysis of the pulsed-field electrophoretic profiles of 30 Streptococcus pyogenes isolates with reduced susceptibilities to ciprofloxacin detected the prevalence of isolates with emm type 6 and considerable genetic diversity among isolates . The mechanism of ciprofloxacin resistance in these isolates was based on point mutations in topoisomerase IV subunit C encoded by parC, mainly replacement of serine-79 by alanine. Antimicrob Agents Chemother, 2005 Jan, 49(1), 398 - 405 The novel parainfluenza virus hemagglutinin-neuraminidase inhibitor BCX 2798 prevents lethal synergism between a paramyxovirus and Streptococcus pneumoniae; Alymova IV et al.; An association exists between respiratory viruses and bacterial infections . Prevention or treatment of the preceding viral infection is a logical goal for reducing this important cause of morbidity and mortality . The ability of the novel, selective parainfluenza virus hemagglutinin-neuraminidase inhibitor BCX 2798 to prevent the synergism between a paramyxovirus and Streptococcus pneumoniae was examined in this study . A model of secondary bacterial pneumonia after infection with a recombinant Sendai virus whose hemagglutinin-neuraminidase gene was replaced with that of human parainfluenza virus type 1 {rSV(hHN)} was established in mice . Challenge of mice with a sublethal dose of S . pneumoniae 7 days after a sublethal infection with rSV(hHN) (synergistic group) caused 100% mortality . Bacterial infection preceding viral infection had no effect on survival . The mean bacterial titers in the synergistic group were significantly higher than in mice infected with bacteria only . The virus titers were similar in mice infected with rSV(hHN) alone and in dually infected mice . Intranasal administration of BCX 2798 at 10 mg/kg per day to the synergistic group of mice starting 4 h before virus infection protected 80% of animals from death . This effect was accompanied by a significant reduction in lung viral and bacterial titers . Treatment of mice 24 h after the rSV(hHN) infection showed no protection against synergistic lethality . Together, our results indicate that parainfluenza viruses can prime for secondary bacterial infections . Prophylaxis of parainfluenza virus infections with antivirals might be an effective strategy for prevention of secondary bacterial complications in humans. Antimicrob Agents Chemother, 2005 Jan, 49(1), 220 - 9 Pharmacokinetics of tigecycline after single and multiple doses in healthy subjects; Muralidharan G et al.; Tigecycline, a novel glycylcycline antibiotic, exhibits strong activity against gram-positive, gram-negative, aerobic, anaerobic, and atypical bacterial species, including many resistant pathogens, i.e., vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae . The safety and tolerability of tigecycline administered as single or multiple doses or at various infusion rates were explored in three phase 1, randomized, double-blind, placebo-controlled studies in healthy subjects . Full pharmacokinetic profiles of tigecycline were determined in two of these studies . Subjects in the single-dose study received 12.5 to 300 mg of tigecycline, which differed with respect to the duration of infusion, subjects' feeding status, and ondansetron pretreatment . Subjects in the ascending multiple-dose study received 25 to 100-mg doses of tigecycline as a 1-h infusion every 12 h . The variable volume and infusion rate study consisted of administration of 100-mg loading dose of tigecycline, followed by 50 mg every 12 h for 5 days . Serum samples were analyzed for tigecycline by validated high-pressure liquid chromatography or liquid chromatography/tandem mass spectrometry methods . Systemic clearance ranged from 0.2 to 0.3 liters/h/kg, and the tigecycline half-life ranged from 37 to 67 h . Tigecycline had a large volume of distribution (7 to 10 liters/kg), indicating extensive distribution into the tissues . Food increased the maximum tolerated single-dose from 100 to 200 mg, but the duration of infusion did not affect tolerability . Side effects, mainly nausea and vomiting, which are common to the tetracycline class of antimicrobial agents, were seen in these studies . Tigecycline exhibits linear pharmacokinetics and is safe and well tolerated in the dose ranges examined. Antimicrob Agents Chemother, 2005 Jan, 49(1), 195 - 201 Pharmacokinetics, serum inhibitory and bactericidal activity, and safety of telavancin in healthy subjects; Shaw JP et al.; The pharmacokinetics, tolerability, and serum inhibitory and bactericidal titers of telavancin, a new rapidly bactericidal lipoglycopeptide with multiple mechanisms of action against gram-positive pathogens, were assessed in a two-part, randomized, double-blind, placebo-controlled, ascending-dose study with 54 healthy men . In part 1, single ascending intravenous doses of 0.25 to 15 mg/kg of body weight were studied . In part 2, multiple ascending doses (30-min infusions of 7.5 to 15 mg/kg/day) were studied over 7 days . Following the administration of multiple doses, steady state was achieved by days 3 to 4 . At day 7 after the administration of telavancin at 7.5, 12.5, and 15 mg/kg/day, peak concentrations in plasma were 96.7, 151.3, and 202.5 microg/ml, respectively, and steady-state area-under-the-curve values were 700, 1,033, and 1,165 microg x h/ml, respectively . The elimination half-life ranged from 6.9 to 9.1 h following the administration of doses > or =5 mg/kg . Most adverse events were mild in severity . At 24 h postinfusion, serum from subjects given telavancin demonstrated potent bactericidal activity against methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae strains . The results suggest that telavancin may be an effective once-daily therapy for serious bacterial infections caused by these pathogens. Antimicrob Agents Chemother, 2005 Jan, 49(1), 188 - 94 Pharmacodynamic profile of telithromycin against macrolide- and fluoroquinolone-resistant Streptococcus pneumoniae in a neutropenic mouse thigh model; Tessier PR et al.; The new ketolide telithromycin has potent in vitro activity against Streptococcus pneumoniae, including strains resistant to penicillin, macrolides, and fluoroquinolones . The aim of the present study was to define the pharmacodynamic profile of telithromycin against S . pneumoniae strains with various resistance profiles in an in vivo system . Ten S . pneumoniae strains were studied; seven exhibited penicillin resistance, six demonstrated macrolide resistance, and two exhibited gatifloxacin resistance . The telithromycin MICs for all isolates were < or =0.5 microg/ml . Using the murine thigh infection model, CD-1/ICR mice were rendered neutropenic and were then inoculated with 10(5) to 10(6) CFU of S . pneumoniae per thigh . Telithromycin was administered orally at doses ranging from 25 to 800 mg/kg of body weight/day, with the doses administered one, two, three, or four times a day . The activity of telithromycin was assessed by determination of the change in the bacterial density in thigh tissue after 24 h of treatment for each treatment group and the untreated controls . Pharmacokinetic studies of telithromycin were conducted in infected, neutropenic animals . The levels of protein binding by telithromycin in mice ranged from 70 to 95% over the observed range of pharmacokinetic concentrations . By using either the total or the free concentrations of telithromycin, the area under the concentration-time curve (AUC)/MIC ratio was a strong determinant of the response against S . pneumoniae, regardless of the phenotypic resistance profile . The maximal efficacy (the 95% effective dose) against this cohort of S . pneumoniae strains and bacterial inhibition (stasis) of telithromycin were predicted by ratios of the AUC for the free drug concentration/MIC of approximately 1,000 and 200, respectively. Glycobiology . 2004 Dec 22; {Epub ahead of print} Identification of a Membrane-Localized Cysteine Cluster near the Substrate Binding Sites of the Streptococcus Equisimilis Hyaluronan Synthase; Kumari K et al.; The membrane-bound hyaluronan synthase (HAS) from Streptococcus equisimilis (seHAS), which is the smallest Class I HAS, has four cysteine residues (positions 226, 262, 281, and 367) that are generally conserved within this family . Although Cys-null seHAS is still active, chemical modification of cysteine residues causes inhibition of wildtype enzyme (Kumari et al., J . Biol . Chem . 277, 13943, 2002) . Here we studied the effects of N-ethylmaleimide (NEM) treatment on a panel of seHAS Cys-mutants to examine the structural and functional roles of the four cysteine residues in the activity of the enzyme . We found that Cys(226), Cys(262), and Cys(281) are reactive with NEM, but that Cys(367) is not . Substrate protection studies of wildtype seHAS and a variety of Cys-mutants revealed that binding of UDP-GlcUA, UDP-GlcNAc or UDP can protect Cys(226) and Cys(262) from NEM inhibition . Inhibition of the six double Cys-mutants of seHAS by sodium arsenite, which can crosslink vicinyl sulfhydryl groups, also supported the conclusion that Cys(262) and Cys(281) are close enough to be crosslinked . Similar results indicated that Cys(281) and Cys(367) are also very close in the active enzyme . We conclude that three of the four Cys residues in seHAS (Cys(262), Cys(281), and Cys(367) ) are clustered very close together, that these Cys residues and Cys(226) are located at the inner surface of the cell membrane, and that Cys(226) and Cys(262) are located in or near a UDP binding site. J Dent Res, 2005 Jan, 84(1), 89 - 93 Inhibition of root caries progression by an antibacterial adhesive; Kuramoto A et al.; A dentin primer containing the antibacterial monomer 12-methacryloyloxydodecylpyridinium bromide (MDPB) has been shown to penetrate and kill the bacteria in artificially demineralized dentin . We hypothesized that an experimental adhesive system, which incorporates the MDPB-containing primer, would be effective in inhibiting the progression of root caries in vitro . Artificial caries lesions were prepared by either an acid-gel or a Streptococcus mutans culture technique on the roots of extracted human teeth . The progression of these lesions after the application of the experimental or proprietary adhesive system was examined . Further demineralization was completely prevented by the experimental adhesive system, while lesions managed with the proprietary materials showed limited ability to inhibit further demineralization . We conclude that the experimental adhesive system can inhibit the progression of root-surface caries in vitro, through a combination of its antimicrobial activity and sealing of the demineralized dentin. J Dent Res, 2005 Jan, 84(1), 48 - 53 Increase in cariogenic bacteria after initial periodontal therapy; De Soete M et al.; This study examined the hypothesis of an intra-oral shift, during initial periodontal therapy, from a periopathogenic to a cariogenic flora . Seventy-one patients with periodontitis were randomly allocated to one of the following treatment strategies: (1) scaling and root planing, quadrant by quadrant, at two-week intervals (NC); (2) full-mouth scaling and root planing within 24 hrs (FRP); or (3) full-mouth disinfection within 24 hrs, including antiseptics {chlorhexidine (CHX) or amine fluoride/stannous fluoride (F) for 2 mos, or CHX for 2 mos followed by F for 6 mos (CHX+F)} . At baseline and after 2, 4, and 8 mos, bacterial samples were taken from supra- and subgingival plaque, saliva, and tongue . The detection frequencies and relative proportions of Streptococcus mutans increased in the NC and FRP groups, but decreased in the F group . In the CHX group, these species disappeared temporarily, but they disappeared for the entire 8 mos in the CHX+F group . These observations were similar for all sample locations . The periopathogens decreased in all groups . This finding confirms the abovementioned hypothesis and indicates a need for caries prophylactic regimens. Srp Arh Celok Lek, 2004 Oct, 132 Suppl 1, 42 - 4 {Erythromycin-resistant Streptococcus pyogenes}; High diversity of group A Streptococcal emm types in an Indian community: the need to tailor multivalent vaccines; Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, IndiaBACKGROUND: Concern about the emergence of antibiotic-resistant strains and about morbidity and/or mortality related to rheumatic fever and rheumatic heart disease has been a continuous impetus for the development of a safe, effective vaccine against group A Streptococcus (GAS) . To date, >120 GAS M types are known, as identified by serological typing . In general, serum immunoglobulin G directed to the hypervariable NH2 terminal portion of M protein leads to complement fixation and opsonophagocytosis of the homologous streptococcal serotype by polymorphonuclear leukocytes, and the protection is type specific . The sequence variation at the N terminus ultimately affects the binding of opsonic antibodies . Because of hypervariability in these opsonic sequences from different M types, it was relevant to use epitopes derived from these multiple sequences in a "multivalent vaccine" design for evaluation of protection against these M types of GAS . Thus, any attempts to design vaccines for a given community will require information on N terminal-sequence typing and variation . METHODS: In the present study, we performed molecular characterization of isolates recovered from patients in northern India--to our knowledge, for the first time--in an attempt to study the circulating M types and their N terminal sequence variability . RESULTS: We report tremendous diversity in GAS strains recovered from symptomatic patients, with implications on the design of appropriate vaccines . Fifty-nine isolates represented 33 different sequence types . Very few novel types and no predominant clones were found . CONCLUSIONS: The high diversity of emm types encountered in a single year suggests that any M protein-based multivalent vaccine would have to be specifically tailored for this region. Can J Cardiol, 2004 Dec, 20(14), 1479 - 80 Primary purulent pericarditis due to group C Streptococcus; McClure RS et al.; In the antibiotic era, purulent pericarditis, an infection associated with high mortality, is uncommon . The causative organism is generally Staphylococcus aureus or Streptococcus pneumoniae arising from contiguous spread or hematogenous dissemination of an underlying infection elsewhere in the body . The present report describes a previously healthy individual who presented with acute infectious pericarditis with the offending organism identified as Lancefield group C Streptococcus equi . After an initial pericardial window was unable to prevent recurrent pericardial effusion, pericardiectomy was performed and the patient slowly recovered from the incident. J Pediatr Nurs, 2004 Oct, 19(5), 357 - 63 A history of neonatal group B streptococcus with its related morbidity and mortality rates in the United States; Dermer P et al.; The history of neonatal sepsis related to early onset group B streptococcus (GBS) emerged in the early 1970s . The neonatal mortality rate was 55% for those neonates with invasive GBS disease . The first adopted guidelines by the medical community to prevent early onset GBS were developed in the 1990s . One year after implementation of the guidelines, the mortality rate dropped to approximately 5% . Despite the great accomplishments in reducing the mortality rate, GBS remains the number one cause of infant morbidity and mortality in the United States. Oral Microbiol Immunol, 2005 Feb, 20(1), 60 - 4 Influence of microparticle formulation on immunogenicity of SYI, a synthetic peptide derived from Streptococcus mutans GbpB; Peacock ZS et al.; Peacock ZS, Barnes LA, King WF, Trantolo DJ, Wise DL, Taubman MA, Smith DJ . Influence of microparticle formulation on immunogenicity of SYI, a synthetic peptide derived from Streptococcus mutans GbpB . Oral Microbiol Immunol 2005: 20: 60-64.(c) Blackwell Munksgaard, 2005 . Subcutaneous immunization with SYI, a peptide construct based on Streptococcus mutans glucan binding protein B (GbpB) residues 113-132, significantly reduces experimental dental caries . Since mucosal immunization may be preferred for human vaccine applications, the present objective was to determine what formulation of SYI combined with polylactide-coglycolide microparticles could give rise to significant levels of salivary IgA antibody reactive with the native GbpB protein . A comparison of the SYI construct, loaded into or mixed with polylactide-coglycolide revealed the SYI-loaded microparticles to induce significant and sustainable levels of salivary and nasal wash IgA antibody to the peptide and the native protein . SYI mixed with unloaded microparticles was less effective in mucosal antibody response induction . These studies indicate that mucosal immunization with the SYI construct can induce salivary IgA antibody to a pathogenesis-associated component of S . mutans if delivered within polylactide-coglycolide microparticles, suggesting that this approach could successfully induce protective salivary immunity to dental caries caused by S . mutans. Oral Microbiol Immunol, 2005 Feb, 20(1), 20 - 4 Mutacin production in Streptococcus mutans genotypes isolated from caries-affected and caries-free individuals; Kamiya RU et al.; Kamiya RU, Napimoga MH, Rosa RT, Hofling JF, Goncalves RB . Mutacin production in Streptococcus mutans genotypes isolated from caries-affected and caries-free individuals . Oral Microbiol Immunol 2005: 20: 20-24.(c) Blackwell Munksgaard, 2005 . Relationships between genetic diversity and mutacin production in Streptococcus mutans were evaluated in 319 clinical isolates from eight caries-affected and eight caries-free individuals . The isolates were submitted to mutacin typing and AP-PCR (arbitrarily primed polymerase chain reaction) assay . The mutacin production was detected for 12 Streptococcus sp . indicator strains . Results showed significant variations in the mutacin production profiles and the inhibitory spectra of both groups . A possible association was seen between mutacin activity and the distinct patterns of Streptococcus sp . colonization in the two groups . Genotyping by AP-PCR using the primers OPA-02 and OPA-13 revealed 101 distinct genotypes against 48 phenotypes identified by mutacin typing . No correlation was observed between the inhibitory spectra of mutacin and genotypic similarities based on AP-PCR analyses . According to our results, strains of the same S . mutans genotype showed different mutacin profiles, suggesting a high degree of interstrain diversity . In conclusion, mutacin production seems to be of clinical importance in the colonization of S . mutans and is highly diversified in the S . mutans species. Mol Microbiol, 2005 Jan, 55(1), 221 - 34 The PerR regulon in peroxide resistance and virulence of Streptococcus pyogenes; Brenot A et al.; Summary Prior studies have shown that the catalase-deficient pathogen Streptococcus pyogenes (group A streptococcus) has a robust ability to resist oxidative stress that partially involves the transcriptional regulator PerR . However, the extent of the PerR regulon and the contribution of the members of this regulon to virulence are unknown . In this study, DNase I footprinting revealed that PerR binds specifically to a single site upstream of the promoter for the gene encoding alkyl hydroperoxide reductase (ahpC) . However, analyses of transcript abundance revealed that while ahpC is regulated in response to growth phase, its regulation is independent of PerR . Instead, PerR regulates transcription of a divergent gene cluster that encodes a putative cold shock protein . The gene encoding the Dps-like peroxide resistance protein MrgA was repressed by PerR, consistent with the presence of a PerR binding site in its promoter . Phenotypic analyses of PerR(-), AhpC(-) and MrgA(-) mutants revealed that while AhpC is not essential for resistance to challenge with hydrogen peroxide in vitro, AhpC does contribute to scavenging of endogenous hydrogen peroxide and is required for virulence in a murine model of infection . In contrast, a MrgA(-) mutant was hypersensitive to challenge with peroxide in vitro, but was fully virulent in all animal models tested . Finally, a PerR(-) mutant was hyper-resistant to peroxide, yet was highly attenuated for virulence in all murine models . These data demonstrate that while a mutant's capacity to resist peroxide stress did not directly correlate with its ability to cause disease, the appropriate regulation of the peroxide stress response is critical for virulence. Can Respir J, 2004 Nov-Dec, 11(8), 589 - 93 Clinical characteristics at initial presentation and impact of dual therapy on the outcome of bacteremic Streptococcus pneumoniae pneumonia in adults; Weiss K et al.; BACKGROUND: Approximately 10% of patients hospitalized with community-acquired pneumonia (CAP) are bacteremic . Bacteremic Streptococcus pneumoniae pneumonia (BSPP) is the number one cause of mortality, representing up to 70% of all CAP deaths . In fact, all CAP guidelines have identified this issue as one of the most important issues when establishing their recommendations . OBJECTIVE: To assess the impact of dual antibiotic therapy in patients with BSPP . PATIENTS AND METHODS: All cases of BSPP in patients 18 years of age and older who were hospitalized from 1995 to 2000 were retrospectively analyzed . The standard initial therapeutic regimen used was cefuroxime with or without a macrolide from 1995 to 1997, and ceftriaxone and azithromycin or clarithromycin from 1998 to 2000 . During the 1995 to 1997 period, only 16% of the patients initially received a macrolide, whereas all patients in the 1998 to 2000 period received a macrolide at admission . RESULTS: Ninety-five patients (49 men, 46 women) with a mean age of 63 years (range 20 to 98 years) were included in the present study . The mean pneumonia severity index at admission was 113 for the monotherapy cohort and 114 for the dual therapy group . At admission, 30.5% of patients had a leukocyte count greater than 20 109/L, 11.5% had a systolic blood pressure less than 90 mmHg, 44.2% had a respiratory rate greater than 30 breaths/min and 33.6% had nausea/vomiting, necessitating some form of therapy or preventing the patient from eating . In addition, 16.8% had no fever at admission . Overall, 72.5% became afebrile within 48 h . Fifteen (15.8%) patients died (four within the first 72 h) . The mortality rate was significantly higher in the monotherapy group (11 of 42 patients; 25.6%) than in the dual therapy cohort (four of 53 patients; 7.5%) (OR 0.23; 95% CI 0.07 to 0.74) . Antibiotic resistance was not associated with increased mortality . CONCLUSION: The combination of ceftriaxone plus a macrolide significantly reduced the mortality rate compared with monotherapy (cefuroxime) in patients with CAP that have the highest mortality rate. Br Dent J, 2004 Nov 27, 197(10), 635 - 40; discussion 623 A comparison of decontamination methods used for dental burs; Whitworth CL et al.; OBJECTIVES: This study investigated the bacterial and fungal contamination of used dental burs . A novel assay system for comparison of efficacy of pre-sterilisation cleaning techniques for dental burs was used to evaluate manual scrubbing, enzymic agents and washer-disinfectors . METHODS: Thirty dental burs contaminated during cavity preparation were analysed for micro-biological total viable counts and species of bacteria and fungi present . To simulate clinically contaminated burs, a culture of Streptococcus sanguis NCTC 7863 was used to inoculate unused dental burs, alone and combined with blood, saliva or a mixture of blood and saliva . Contaminated burs were subjected to six pre-sterilisation cleaning techniques and the log reduction in contamination achieved by each method was assessed . RESULTS: The microbial count from used dental burs ranged from 0 to 6.92 x 10(4) CFU ml(-1) . Many potentially pathogenic species were identified . The decontamination assay demonstrated that autoclaving alone was not sufficient to sterilise dental burs . Manual scrubbing in air was less efficacious than manual scrubbing under water (p<0.001) . The most effective method of pre-sterilisation cleaning for dental burs was a washer-disinfector . CONCLUSIONS: Enzymic agents are suitable for soaking contaminated dental burs immediately after use . Washer-disinfectors are recommended as the method of choice for pre-sterilisation cleaning of contaminated dental burs. Br Dent J . 2004 Nov 27;197(10):623. Decontamination of dental burs; Smith AJ; ObjectivesThis study investigated the bacterial and fungal contamination of used dental burs . A novel assay system for comparison of efficacy of pre-sterilisation cleaning techniques for dental burs was used to evaluate manual scrubbing, enzymic agents and washer-disinfectors.MethodsThirty dental burs contaminated during cavity preparation were analysed for micro-biological total viable counts and species of bacteria and fungi present . To simulate clinically contaminated burs, a culture of Streptococcus sanguis NCTC 7863 was used to inoculate unused dental burs, alone and combined with blood, saliva or a mixture of blood and saliva . Contaminated burs were subjected to six pre-sterilisation cleaning techniques and the log reduction in contamination achieved by each method was assessed.ResultsThe microbial count from used dental burs ranged from 0 to 6.92x10(4) CFU ml(-1) . Many potentially pathogenic species were identified . The decontamination assay demonstrated that autoclaving alone was not sufficient to sterilise dental burs . Manual scrubbing in air was less efficacious than manual scrubbing under water (p<0.001) . The most effective method of pre-sterilisation cleaning for dental burs was a washer-disinfector.ConclusionsEnzymic agents are suitable for soaking contaminated dental burs immediately after use . Washer-disinfectors are recommended as the method of choice for pre-sterilisation cleaning of contaminated dental burs. Presse Med, 2004 Nov 20, 33(20), 1425 - 30 {Type of child care and nasopharyngeal S . pneumoniae and H . influenzae carriage in children in the Alpes-Maritimes.}; Dunais B et al.; OBJECTIVE: To compare the prevalence rates of nasopharyngeal carriage of Streptococcus pneumoniae (SP) and of SP with diminished susceptibility to penicillin (PDSP) according to two types of day care, i.e . children in group day-care (GDC) and those attended by a child minder (CM) before and after the implementation of a local public health campaign promoting prudent antibiotic use in pediatric care . METHODS: Two cross sectional studies were conducted in each care setting in 1999, 2000 and 2002, on a random sample of children . RESULTS: Initial prevalence rates for SP before the campaign were 54% in the GDC group in 1999 and 34% in the CM group in 2000, with 63% and 52% PDSP, respectively . In 2002 theses rates were 58 and 33% for SP (p<10(-5)) and 64 and 53% for PDSP, respectively . The proportion of children who received antibiotics decreased in both care settings between the two surveys, from 47 to 37% in the CM group (p=0.03) and from 60 to 51% in the GDC group (p=0.03) . CONCLUSION: These results are in favor of the child minder setting and also illustrate the positive impact of a public health campaign on the frequency of antibiotic prescriptions. J Immunol, 2005 Jan 1, 174(1), 426 - 34 Morphine impairs host innate immune response and increases susceptibility to Streptococcus pneumoniae lung infection; Wang J et al.; Chronic morphine use impairs host innate immune response and increases susceptibility to bacteria and virus . In this study a novel mouse model of chronic morphine treatment, followed by intranasal inoculation with Streptococcus pneumoniae, was used to investigate microbial events and host innate immune response . Our results show that chronic morphine treatment markedly delayed neutrophil recruitment and increased bacterial burden in the lung, spleen, and blood with a subsequent increase in mortality . In morphine-treated animals, before neutrophil recruitment, a significant decrease in TNF-alpha, IL-1, IL-6, MIP-2, and KC was observed both in bronchoalveolar lavage fluids and in lung tissue . In the early phase of infection, we found that accumulation of galectin-3 in the alveolar space of streptococcus-infected lungs was decreased after morphine treatment . The transcription factor NF-kappaB in lung resident cells was also inhibited after morphine treatment . Taken together, these results suggest that chronic morphine treatment in an S . pneumoniae infection model suppresses NF-kappaB gene transcription in lung resident cells, which, in turn, modulates the transcriptional regulation of MIP-2 and inflammatory cytokines . The decreased synthesis of MIP-2 and inflammatory cytokines coupled with the decreased release of galectin-3 result in reduced migration of neutrophils to the site of infection, thereby increasing susceptibility to S . pneumoniae infection after morphine treatment. Genetics, 2004 Dec, 168(4), 1795 - 803 Patterns of sequence divergence in 5' intergenic spacers and linked coding regions in 10 species of pathogenic bacteria reveal distinct recombinational histories; Hughes AL et al.; We compared the pattern of nucleotide difference in 8034 genes and in their 5' intergenic spacers between conspecific pairs of genomes from 10 species of pathogenic bacteria . Certain genes or spacers showed much greater sequence divergence between the genotypes compared to others; such divergent regions plausibly originated by recombinational events by which a gene and/or spacers was donated from a divergent genome . Different patterns of divergence in genes and spacers identified different recombinational patterns . For example, in Chlamydophila pneumoniae, there were examples of both unusually divergent spacers and unusually divergent genes, but there were no cases in which a gene and its spacer were both unusually divergent . This pattern suggests that, in C . pneumoniae, recombination events have broken up the linkage between genes and 5' spacers . By contrast, in Streptococcus agalactiae, there were a number of cases in which both spacer and gene were unusually divergent, indicating that a number of large-scale recombination events that included both genes and 5' spacers have occurred; there was evidence of at least two large-scale recombination events in the genomic region including the pur genes in S . agalactiae. Drugs, 2005, 65(1), 121 - 36 Amoxicillin/Clavulanic Acid 2000mg/125mg Extended Release (XR): A Review of its Use in the Treatment of Respiratory Tract Infections in Adults; McCormack PL et al.; Amoxicillin/clavulanic acid 2000mg/125mg extended release (Augmentin XRtrade mark), referred to herein as amoxicillin/clavulanic acid XR, is a pharmacokinetically enhanced formulation designed to provide more effective therapy in adults and adolescents than conventional formulations against community-acquired respiratory tract pathogens, particularly Streptococcus pneumoniae, with reduced susceptibility to amoxicillin.Amoxicillin/clavulanic acid XR maintains plasma amoxicillin concentra