Streptococcal

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 concentrations above 4 microg/mL for a mean of 49% of the dosing interval indicating that it would be highly effective against S . pneumoniae strains with minimum inhibitory concentrations (MICs) above the National Committee for Clinical Laboratory Standard's amoxicillin +/- clavulanic acid susceptibility breakpoint of </=2 microg/mL . Amoxicillin/clavulanic acid XR is at least as effective as conventional amoxicillin/clavulanic acid formulations, levofloxacin and clarithromycin in treating community-acquired pneumonia, acute bacterial sinusitis or acute exacerbations of chronic bronchitis, and has a tolerability profile comparable to that of conventional amoxicillin/clavulanic acid formulations . While the incidence of amoxicillin- or multidrug-resistant S . pneumoniae is not currently sufficient in most regions to warrant the routine empirical use of amoxicillin/clavulanic acid XR, the drug would be extremely useful in those regions with a high incidence of resistant pathogens or in selected patients (i.e . those with S . pneumoniae isolates having amoxicillin MICs >/=2 microg/mL but </=4 microg/mL).

Biochemistry, 2004 Dec 28, 43(51), 16461 - 6
Streptococcus pneumoniae isoprenoid biosynthesis is downregulated by diphosphomevalonate: an antimicrobial target; Andreassi JL 2nd et al.; The toll that Streptococcus pneumoniae exacts on the welfare of humanity is enormous . This organism claims the lives of approximately 3700 people daily, the majority of whom are children below the age of 5, and the situation could worsen due to the increasing incidence of pernicious, multiple-antibiotic-resistant strains . Here we report the discovery and characterization of a new allosteric site, shown to be absent in humans, that can be used to switch off an essential pathway in S . pneumoniae, the mevalonate pathway . Diphosphomevalonate (DPM), an intermediate in the pathway, binds with high affinity (K(d) = 530 nM) to mevalonate kinase, the first enzyme in the pathway, and inactivates it . Steady-state and equilibrium binding measurements reveal that DPM binding is noncompetitive versus substrates . DPM binds at an allosteric site, and inhibition cannot be overcome by an increasing substrate concentration . The DPM-binding site is a promising target for the development of new antimicrobial agents.

Intern Med, 2004 Nov, 43(11), 1029 - 33
Clinical characteristics of pneumonia caused by penicillin resistant and sensitive Streptococcus pneumoniae in Japan; Yanagihara K et al.; BACKGROUND: S . pneumoniae is the leading cause of morbidity and mortality worldwide . P-lactam antibiotics were very effective against S . pneumoniae, however resistance to this class of antibiotic has become an increasing problem . OBJECTIVES: To assess the clinical differences between penicillin-sensitive and penicillin-resistant pneumococcal pneumonia . METHODS: The medical records of 306 patients with pneumococcal pneumonia who visited Nagasaki University Hospital or affiliated institutions between January 1997 and December 2001 were retrospectively reviewed . The Pneumonia Severity Index (PSI), sensitivity of S . pneumoniae, antibiotic choices and information on clinical outcome were evaluated . RESULTS: Penicillin sensitive and resistant organisms were responsible for 177 (57.7%) and 129 (42.0%) cases of pneumonia, respectively . The median age of patients was 65.5 years, and 72.3% (222) were males . There were no significant differences in the resistance rate between elderly (>65 years) and young patients . The median PSI score was 76 . No significant association was observed between the severity of illness and sensitivities of S . pneumoniae . Previous use of beta-lactams in the last 3 months and chronic obstructive pulmonary disease were associated with penicillin resistance . The failure rate of first line antibiotics was significantly higher in the resistant group (22.5%) than in the sensitive group (9.0%) . Four of 306 patients died (mortality, 1.3%) . CONCLUSION: There were no significant differences clinically between the penicillin-sensitive and penicillin-resistant groups . The failure rate of first line antibiotics was higher in the resistant than in the sensitive group . Thus, the selection of antimicrobial agents should be carefully considered in the context of the patient's risk factors.

Chemotherapy, 2004 Dec, 50(6), 297 - 301 Epub 2004 Dec 08.
Left atrial myxoma prolapsing into the left ventricle . Case report and review of the literature; Karachalios G et al.; Cardiac myxomas are rare tumors which may present differently . Left atrial myxoma is an entity from anatomopathological and clinical aspects . To the best of our knowledge, only 2 cases of infected left atrial myxomas treated surgically have been reported in the last 6 years . Herein, we present a patient with a left atrial myxoma prolapsing into the left ventricle in the diastolic phase, which was infected with Streptococcus viridans . Combined therapy, consisting of surgical management and antimicrobial therapy, was used . Clinical presentation, diagnosis and treatment are reviewed . 2004 S . Karger AG, Basel.

FEMS Immunol Med Microbiol, 2005 Jan 1, 43(1), 73 - 80
PiuA and PiaA, iron uptake lipoproteins of Streptococcus pneumoniae, elicit serotype independent antibody responses following human pneumococcal septicaemia; Whalan RH et al.; Streptococcus pneumoniae causes considerable morbidity and mortality worldwide . The need for a cheap and effective pneumococcal vaccine has necessitated the evaluation of common virulence-associated proteins as potential vaccine antigens . PiuA and PiaA are the lipoprotein components of two pneumococcal iron ABC transporters . Here, we show that patients with culture confirmed pneumococcal septicaemia have elevated levels of antibody to PiuA and PiaA in convalescent-phase, compared with acute-phase serum . Additionally, sera from septicaemic patients infected with 13 pneumococcal strains covering eight different serotypes, cross-reacted with recombinant PiuA-His(6) and PiaA-His(6) from a single pneumococcal strain, indicating that this immune response is serotype independent . Anti-PiuA and anti-PiaA antibodies were also found in healthy seven-month-old infants, indicating that they are immunogenic at a very early age.

J Vet Med B Infect Dis Vet Public Health, 2004 Dec, 51(10), 455 - 458
Multiplex Polymerase Chain Reaction for Identification and Differentiation of Streptococcus equi subsp . zooepidemicus and Streptococcus equi subsp . equi; Alber J et al.; Summary The closely related streptococcal species Streptococcus equi subsp . zooepidemicus and S . equi subsp . equi were identified by polymerase chain reaction using oligonucleotide primers designed according to species-specific parts of the superoxide dismutase A encoding gene sodA . A further differentiation of both subspecies could be performed by amplification of the genes seeH and seeI encoding the exotoxins SeeH and SeeI, respectively, which could be detected for S . equi subsp . equi but not for S . equi subsp . zooepidemicus . A further simplification of the identification and differentiation of both subspecies was conducted by sodA-seeI multiplex polymerase chain reaction.

Clin Microbiol Infect, 2004 Dec, 10(12), 1037 - 9
Streptococcus pneumoniae septic arthritis in adults; Baraboutis I et al.; Streptococcus pneumoniae septic arthritis is an uncommon infection . The classic clinical picture is that of concomitant pulmonary and/or meningeal and joint infections in the presence of predisposing local and systemic factors . Initial laboratory tests are usually inconclusive, and joint aspiration is required for a definitive diagnosis . Treatment options include antibiotic therapy (usually with penicillin) combined with closed or open joint drainage . Increasing reports of infections involving penicillin-resistant strains are a concern . The prognosis is usually favourable, but early recognition and aggressive management are essential to reduce the likelihood of significant joint injury.

Treat Respir Med, 2004, 3(5), 329 - 36
Comparative efficacies and tolerabilities of intravenous azithromycin plus ceftriaxone and intravenous levofloxacin with step-down oral therapy for hospitalized patients with moderate to severe community-acquired pneumonia; Zervos M et al.; OBJECTIVE: To compare the efficacy and tolerability of ceftriaxone plus azithromycin with those of levofloxacin in the treatment of hospitalized patients with moderate to severe community-acquired pneumonia (CAP) . DESIGN: Randomized, open-label multicenter trial with 1 : 1 treatment allocation in an inpatient setting . PATIENTS: 212 male or female inpatients with a clinical diagnosis of CAP were included in the study . In each treatment group >50% of patients had a pneumonia severity index of IV or V . INTERVENTIONS: Open-label treatment with either intravenous (IV) ceftriaxone 1g and IV azithromycin 500 mg daily or IV levofloxacin 500 mg daily . Patients who improved clinically were switched to oral follow-on therapy with either azithromycin 500 mg/day or levofloxacin 500 mg/day . At the clinician's discretion, oral cefuroxime axetil was added to the treatment regimen of patients who received oral azithromycin if a macrolide resistant pneumococcal isolate was documented . RESULTS: Overall, both study treatments were well tolerated . Favorable clinical outcomes in clinically evaluable patients were demonstrated in 91.5% of patients treated with ceftriaxone plus azithromycin and 89.3% (95% CI -7.1%, 11.4%) of patients treated with levofloxacin at the end of therapy visit and in 89.2% and 85.1% (95% CI -6.7%, 14.8%) patients, respectively, at the end of study visit . Bacteriological eradication rates for both treatments were equivalent with the exception of Streptococcus pneumoniae; 44% of isolates were eradicated with levofloxacin compared with 100% of isolates with ceftriaxone plus azithromycin . CONCLUSIONS: As acknowledged by international CAP treatment guidelines, the combination of a third-generation cephalosporin and a macrolide is at least as efficacious as monotherapy with a fluoroquinolone with enhanced anti-pneumococcal activity, for hospitalized patients with moderate to severe CAP . Combined medication with a macrolide and third-generation cephalosporin may be preferred over fluoroquinolones as first-line therapy of hospitalized patients with CAP to minimize the development of multiresistant nosocomial Gram-negative bacilli.

Rev Laryngol Otol Rhinol (Bord), 2004, 125(3), 165 - 9
Treatment of acute mastoiditis: report of 31 cases over a ten year period; Mustafa A et al.; OBJECTIVE: With possible extracranial and intracranial complications, acute mastoiditis is the leading complication of acute otitis media (AOM) . The goal of this study is to assess the clinical features, pathogens, complications and especially management of acute mastoiditis in the ENT service, University Hospital of Strasbourg, France . METHODS: Systematic review of all medical records of patients who were admitted with acute mastoiditis from January 1993 to April 2003 . RESULTS: 31 patients, 18 male (58%) and 13 female (42%) fulfilled inclusion criteria . The average age was 16, going from 6 months to 70 years, with 55% between 0 to 5 years . Most common symptom was otalgia (84%), 58% of patients had history of past AOM and 61% were under antibiotic therapy during admission . Twenty-three patients (74%) presented retroauricular swelling and erythema . 18 (58%) had a displaced pinna . Cultures taken from pus isolated Streptococcus pneumoniae in 12 cases (38.7%), Pseudomonas aeruginosa in 2 cases (6.4%), Streptococcus beta-haemolyticuis 1 case, Staphylococcus coagulase-positive 1 case and Mycobacterium tuberculosis hominis 1 case (3%) . Complications of acute mastoiditis occurred in 3 cases (10%): Meningitis 2 cases and facial nerve paralysis 1 case . Surgery therapy was periformed in 84% of cases (mastoidectomy only or in combination with myringotomy with tube insertion) and medical therapy only in 16% of cases . CONCLUSION: Despite use of antibiotics, acute mastoiditis remains still a threat for patients with AOM, especially for children under 5 years of age . Great care is required from clinicians to make an early diagnosis in order to promote adequate management and prevent complications.

Cardiovasc Intervent Radiol . 2004 Nov 25; {Epub ahead of print}
Endovascular Stent-Grafting for Infected Iliac Artery Pseudoaneurysms; Sanada J et al.; We report two cases of acutely infected pseudoaneurysms of the iliac arteries, successfully treated with endovascular stent-grafting . Two patients underwent stent-graft treatment for erosive rupture of the iliac artery caused by surrounding infection . The first case is that of a 61-year-old man who had undergone Miles' operation for an advanced rectal cancer . Postoperatively, he developed intrapelvic abscess formation, from which methicillin-resistant Staphylococcus aureus was cultured, followed by rupture of the right external iliac artery . The second case is that of a 60-year-old man who had a pseudoaneurysm of the left common iliac artery, which was contiguous with a left psoas muscle abscess, from which Streptococcus agalactiae was cultured . Both patients were successfully treated with only a stent-graft and antibiotic therapy, and remained symptom-free 12 months and 10 months later . Although endovascular stent-grafting should not be considered standard therapy for infected aneurysms, our cases suggest that it can result in repair of infected aneurysms even in the uncontrolled active stage.

BMC Infect Dis . 2004 Dec 16;4(1):60.
Streptococcal necrotising fasciitis from diverse strains of Streptococcus pyogenes in tropical northern Australia: case series and comparison with the literature; Hassell M et al.; BACKGROUND: Since the mid-1980's there has been a worldwide resurgence of severe disease from group A streptococcus (GAS), with clonal clusters implicated in Europe and the United States . However GAS associated sepsis and rheumatic fever have always remained at high levels in many less developed countries . In this context we aimed to study GAS necrotising fasciitis (NF) in a region where there are high background rates of GAS carriage and disease . METHODS: We describe the epidemiology, clinical and laboratory features of 14 consecutive cases of GAS NF treated over a seven year period from tropical northern Australia . RESULTS: Incidence rates of GAS NF in the Aboriginal population were up to five times those previously published from other countries . Clinical features were similar to those described elsewhere, with 7/14 (50%) bacteremic and 9/14 (64%) having associated streptococcal toxic shock syndrome . 11/14 (79%) had underlying chronic illnesses, including all four fatalities (29% mortality overall) . Important laboratory differences from other series were that leukocytosis was absent in 9/14 (64%) but all had substantial lymphopenia . Sequence typing of the 14 NF-associated GAS isolates showed no clonality, with only one emm type 1 and two emm type 3 strains . CONCLUSIONS: While NF clusters can occur from a single emergent GAS clone, this was not evident in our tropical region, where high rates of NF parallel high overall rates of GAS infection from a wide diversity of strains . The specific virulence factors of GAS strains which do cause NF and the basis of the inadequate host response in those patients who develop NF on infection with these GAS require further elucidation.

Sichuan Da Xue Xue Bao Yi Xue Ban, 2003 Jan, 34(1), 135 - 7
{The effects of traditional Chinese medicines on the adherence of Streptococcus mutans to salivary acquired pellicle in vitro}; Huang Z et al.; OBJECTIVES: To investigate the effects of traditional Chinese medicines on the preliminary adherence of Streptococcus mutans to salivary acquired pellicles . METHODS: The hydroxyapatites beads were coated by saliva to form S-HA, an in vitro model of experimental pellicle . Streptococcus mutans was chosen as the experiment strain, and radiolabeled with 3H-thymidine . Two parts of adherence inhibit study were carried on with medicines pretreated S-HA and medicines pretreated bacteria . The numbers of 3H-thymidine labeled bacteria attached to S-HA were counted by scintillation counting to indicate the amount of adherence . RESULTS: It was found that most of the traditional Chinese medicines tested could inhibit the adherence to S-HA to different extent, especially the Galla Chinensis, which has significant inhibitory action . CONCLUSION: Galla Chinensis may be a prospective medicine to inhibit the cariogenic bacteria's preliminary adherence to salivary acquired pellicles.

Arch Oral Biol, 2005 Jan, 50(1), 39 - 48
Microflora cultivable from minocycline strips placed in persisting periodontal pockets; Leung WK et al.; OBJECTIVE:: The microflora that develops on minocycline strips, used as an adjunct in non-surgical periodontal therapy was studied . DESIGN AND METHODS:: Minocycline (1.4mg in polycaprolactone vehicle) and control strips were applied into all residual pockets (PD >/= 5mm, >/=2 pockets/subject) of patients with chronic periodontitis 1 month after a course of non-surgical periodontal therapy . Strips were inserted and retained for 3 days, changed to new strips for 3 more days and then removed . Strips were recovered from 14 (eight test, six control) of the 34 participants at day 0 (strip inserted, left for 30s, removed), days 3 and 6, for (i) anaerobic culture, (ii) coliforms culture, using MacConkey agar, (iii) yeast culture, using Sabouraud's dextrose agar . RESULTS:: The mean anaerobic cfu/strip (x10(5); control/test) were 2/6, 24/2, 11/2 at days 0, 3 and 6, respectively (P > 0.05) . The corresponding mean proportion of Gram-negative rods and fusiforms were 27%/21%, 27%/15% and 55%/8% . The proportions of Gram-negative rods on test strips by day 6 were significantly reduced (P < 0.05) . A significantly increased prevalence of Streptococcus mitis biovar 1 was found on spent test strips (control versus test; 0% versus 38%, Fisher exact test, P = 0.01) . Coliform prevalence at days 0, 3 and 6 on control/test strips were 0/13%, 50%/38% and 50%/13% . Yeasts were occasionally isolated . CONCLUSIONS:: The findings indicated that the minocycline strips but not the control strip supported a microbial colonisation compatible with periodontal health by day 6.

J Biol Chem . 2004 Dec 13; {Epub ahead of print}
Crystal structure of a peptidoglycan synthesis regulatory factor (PBP3) from Streptococcus pneumoniae; Morlot C et al.; Penicillin-binding proteins (PBPs) are membrane-associated enzymes which perform critical functions in the bacterial cell division process . The single D-ala,D-ala (D, D) carboxypeptidase in Streptococcus pneumoniae, PBP3, has been shown to play a key role in control of availability of the peptidoglycal substrate during cell growth . Here, we have biochemically characterized and solved the crystal structure of a soluble form of PBP3 to 2.8 A resolution . PBP3 folds into an N-terminal, D,D carboxypeptidase-like domain, and a C-terminal, elongated b-rich region . The carboxypeptidase domain harbors the classic signature of the penicilloyl serine transferase superfamily, in that it contains a central, 5 stranded antiparallel b-sheet surrounded by a-helices . As in other carboxypeptidases which are present in species whose peptidoglycan stem peptide has a lysine residue at the third position, PBP3 has a 14-residue insertion at the level of its omega loop, a feature which distinguishes it from carboxypeptidases from bacteria whose peptidoglycan harbors a diaminopimelate moiety at this position . PBP3 performs substrate acylation in a highly efficient manner (kcat/Km=50,500 M-1.s-1), an event which may be linked to its central role in control of pneumococcal peptidoglycan reticulation . A model which places PBP3 poised vertically on the bacterial membrane suggests that its C-terminal region could act as a pedestal, placing the active site in proximity to the peptidoglycan and allowing the protein to "skid" on the surface of the membrane, trimming pentapeptides during the cell growth and division processes.

Pathol Biol (Paris), 2004 Dec, 52(10), 607 - 616

Cattoir V.
Bacteria can resist to antibiotics by active exportation mediated by membrane transporters called efflux pumps . These proteins can be specific of a class of antibiotics or responsible for multidrug resistance (MDR) . Energy required by efflux pumps can be provided by transmembrane electrochemical gradient of protons (MFS, RND, SMR families) or sodium ions (MATE family) or by ATP hydrolysis (ABC family) . Several physiological functions have been described in prokaryotes, such as protection from environmental toxics and regulation of cell homeostasis, which can indirectly contributes to bacterial virulence . In Gram-negative bacteria, efflux transporters usually are organized as multicomponent systems in wich the efflux pump located in the inner membrane works in conjunction with a periplasmic fusion protein and an outer membrane factor . The most frequently encountered pumps are of the RND-type such as AcrB in Escherichia coli or MexB in Pseudomonas aeruginosa . In Gram-positive bacteria, efflux is solely mediated by the pump protein, so described with MFS pumps such as NorA or QacA in Staphylococcus aureus and PmrA in Streptococcus pneumoniae . Efflux transporters have also been described in mycobacteria . Although numerous bacterial pumps have been characterized, the clinical consequences of efflux-mediated resistance are mostly unknown because of variable levels of expression and of the lack of specific markers in laboratory practice . Finally, associating pump-specific inhibitors to efflux-sensitive antibiotics might prove an interesting therapeutic perspective . However, inhibitors that are not toxic to eukaryotic cells remain to be identified.

Tidsskr Nor Laegeforen, 2004 Dec 2, 124(23), 3075 - 7
{A 34-year-old man with hemorrhagic cystitis}; Brugger-Andersen T et al.; BACKGROUND: A 34-year-old male presented with macroscopic haematuria, abdominal pain and dysuria while being treated with penicillin for bacterial endocarditis . All blood cultures yielded Streptococcus mutans . After four weeks of treatment he developed haemorrhagic cystitis, thrombophlebitis and eosinophilia . The symptoms disappeared when he was taken off penicillin . After change of medication to ceftriaxone, the patient developed reversible neutropenia and recovered completely . INTERPRETATION: Haemorrhagic cystitis caused by penicillin can be potentially fatal; two cases have earlier been described . Because of cross reaction this patient also developed reversible neutropenia . It is well known that beta-lactam antibiotics can induce severe neutropenia.

Eur J Clin Microbiol Infect Dis . 2004 Dec 9; {Epub ahead of print}
Ciprofloxacin treatment failure in a patient with resistant Streptococcus pneumoniae infection following prior ciprofloxacin therapy; Pletz MW et al.; Reported here is the case of a patient with underlying chronic obstructive pulmonary disease (COPD) in whom ciprofloxacin treatment of a lower respiratory tract infection failed subsequent to ciprofloxacin treatment of an exacerbation of COPD several weeks earlier . During the second course of ciprofloxacin therapy, the patient's condition continued to deteriorate, and she was admitted to the intensive care unit . Bilateral pneumonia was diagnosed . Streptococcus pneumoniae, serotype 11A, resistant to ciprofloxacin was isolated from the sputum . Sequencing revealed a S79F mutation in parC and there was evidence of an efflux pump . The patient improved rapidly after administration of azithromycin and ampicillin/sulbactam . This report of treatment failure due to ciprofloxacin-resistant Streptococcus pneumoniae shows that fluoroquinolones should be avoided when treating patients who have recently received this class of antibiotics.

J Dairy Sci, 2005 Jan, 88(1), 406 - 10
Efficacy of an Iodophore Teat Disinfectant Against Staphylococcus aureus and Streptococcus agalactiae in Experimental Challenge; Leslie KE et al.; A 1.0% iodophore teat disinfectant (Full-Bac) was evaluated in comparison with a positive control (Bovadine), a commercially available 1.0% iodophore teat disinfectant . The study was conducted under conditions of experimental challenge, following the guidelines recommended by the National Mastitis Council . The test product and a positive control were compared in 41 cows, with 82 teats receiving each product at milking, during a 10-wk study period . There were no differences between the test product and the positive control in new intramammary infections due to Staphylococcus aureus, which averaged 13.4% in each of the 2 treatment groups . Additionally, no statistical difference was seen between the test product and positive control in new intramammary infections by Streptococcus agalactiae, which averaged 8.5 and 6.1% for the Full-Bac and Bovadine groups, respectively . Teat skin and teat end condition scores were statistically evaluated at wk 1, 5, and 9 of the study, and no significant differences were observed between the treatment groups . The test teat disinfectant provided similar germicidal activity to that of the positive control teat disinfectant with no adverse effects on teat skin or teat end condition during the warm-season study period.

J Matern Fetal Neonatal Med, 2004, 16 Suppl 2, 9 - 12
Cervicovaginal infections during pregnancy: epidemiological and microbiological aspects; Benedetto C et al.; Objective: The assessment of the association of cervicovaginal infections during pregnancy with preterm (pPROM) and term (PROM) premature rupture of membranes, preterm delivery, mid-trimester miscarriage and intrauterine death, and the definition of the risk factors that identify pregnant women who should have a cervicovaginal culture . Methods: We retrospectively studied the relationship between pregnancy outcomes and cervicovaginal infections in 3217 pregnant women between January 1998 and December 1999 . Microbiological assessment included Gram staining and specific cultures; bacterial vaginosis was diagnosed by Amsel's criteria . We also studied the medical, obstetric, sexual, demographic and social history of 11 212 pregnant women who underwent cervicovaginal culture between January 1992 and December 2001 . Results: Overall, 1425 of the 3217 cultures (44.3%) were positive . The micro-organisms most frequently found were: yeasts (44%), Ureaplasma urealiticum (29%); group B streptococcus (15%); and bacterial vaginosis (11%) . Cervicovaginal cultures were found positive in 84.6% of pPROM, 55.0% of PROM, 50.8% of preterm deliveries, 43.8% of mid-trimester miscarriages, 31.4% of intrauterine deaths and in 33.5% of controls . Among the 11 212 cervicovaginal cultures considered in the second study, an overall 6301 (56.2%) were positive, 2711 (43%) in asymptomatic women . Cervicovaginal infections were associated with country of origin, age under 25 years, age at first intercourse under 15 years, more than ten partners, more than one partner in the past 6 months, prior abortions, past sexually transmitted diseases (STDs) and HIV infection . Conclusion: Cervicovaginal infections were significantly associated with PROM (p < 0.0001), pPROM (p < 0.0001) and preterm delivery (p < 0.0001), but not with intrauterine death . The association with mid-trimester miscarriage approached statistical significance (p = 0.06) . The main risk factors for cervicovaginal infections were country of origin, age under 25 years, age at first intercourse under 15 years, more than ten partners, more than one partner in the past 6 months, prior abortions, past STDs and HIV infection.

J Microbiol Methods, 2005 Feb, 60(2), 189 - 93
A novel selective medium for isolation of Streptococcus mutans; Takada K et al.; The aim of this study was to improve the selective medium of Streptococcus mutans . A new selective medium, designated MS-MUTV, was prepared by adding 10 mg/l valinomycin to the MS-MUT medium previously described . The average recovery of S . mutans was 72.1%, and the growth of S . sobrinus and S . anginousus group was inhibited on MS-MUTV, but allowed on MS-MUT . One hundred and thirty-nine human saliva samples were examined and counted for S . mutans and non-S . mutans colonies . The recovery of S . mutans on MS-MUTV was similar to that on MS-MUT . Eighty-two and 7.9 percent of the saliva samples obtained S . mutans pure cultures, with no bacterial growth on MS-MUTV, respectively . The remaining 10.1% were contaminated with non-S . mutans, with low-level CFU . MS-MUTV is useful for the isolation of S . mutans alone from clinical samples in routine examinations.

J Med Chem, 2004 Dec 16, 47(26), 6499 - 508
Inhibition of Streptococcus suis adhesion by dendritic galabiose compounds at low nanomolar concentration; Joosten JA et al.; A series of mono-, di-, and tetravalent galabiose (Galalpha1-4Gal) compounds were synthesized in good yields by coupling of a general carboxylic acid-bearing sugar building block to dendritic scaffolds based on the 3,5-di-(2-aminoethoxy)benzoic acid branching unit . Furthermore, a poly(amidoamine)- (PAMAM-) based dendritic galabioside was synthesized containing eight galabiose units . All galabiosides were tested in a hemagglutination assay and a surface plasmon resonance (SPR) competition assay in order to establish their potency in the binding to the bacterial Gram-positive pathogen Streptococcus suis . A monovalent galabioside containing a short spacer was used as a reference compound in all the assays . Variations in the scaffold as well as in the spacer arms were introduced to determine their influence on the inhibition . The best inhibitor of hemagglutination was an octavalent galabioside with a minimal inhibitory concentration (MIC) of 0.3 nM, to the best of our knowledge the first example of inhibition of bacterial binding by a soluble carbohydrate at a subnanomolar concentration.

J Vet Med Sci, 2004 Nov, 66(11), 1467 - 70
ARDRA and RAPD analyses of human and animal isolates of Streptococcus gallolyticus; Sasaki E et al.; A total of 23 Streptococcus gallolyticus strains, consisting of 12 strains from feces of healthy animals and 11 from clinical cases of human or cow mastitis milk, were examined genealogically . Four strains of S . bovis "biotype II/1" and 3 strains of S . equinus, the closely related organisms to S . gallolyticus, were also analyzed for outgroup comparison . Neither the amplified ribosomal DNA restriction analysis (ARDRA) nor the randomly amplified polymorphic DNA (RAPD) analysis that had been designed to recognize S . gallolyticus strains virulent in pigeons could differentiate clinical strains from the others of S . gallolyticus . No correspondence between the DNA profile in either analysis and the host animal species was detected.

J Immunol, 2004 Dec 15, 173(12), 7506 - 12
The virulence function of Streptococcus pneumoniae surface protein A involves inhibition of complement activation and impairment of complement receptor-mediated protection; Ren B et al.; Complement is important for elimination of invasive microbes from the host, an action achieved largely through interaction of complement-decorated pathogens with various complement receptors (CR) on phagocytes . Pneumococcal surface protein A (PspA) has been shown to interfere with complement deposition onto pneumococci, but to date the impact of PspA on CR-mediated host defense is unknown . To gauge the contribution of CRs to host defense against pneumococci and to decipher the impact of PspA on CR-dependent host defense, wild-type C57BL/6J mice and mutant mice lacking CR types 1 and 2 (CR1/2(-/-)), CR3 (CR3(-/-)), or CR4 (CR4(-/-)) were challenged with WU2, a PspA(+) capsular serotype 3 pneumococcus, and its PspA(-) mutant JY1119 . Pneumococci also were used to challenge factor D-deficient (FD(-/-)), LFA-1-deficient (LFA-1(-/-)), and CD18-deficient (CD18(-/-)) mice . We found that FD(-/-), CR3(-/-), and CR4(-/-) mice had significantly decreased longevity and survival rate upon infection with WU2 . In comparison, PspA(-) pneumococci were virulent only in FD(-/-) and CR1/2(-/-) mice . Normal mouse serum supported more C3 deposition on pneumococci than FD(-/-) serum, and more iC3b was deposited onto the PspA(-) than the PspA(+) strain . The combined results confirm earlier conclusions that the alternative pathway of complement activation is indispensable for innate immunity against pneumococcal infection and that PspA interferes with the protective role of the alternative pathway . Our new results suggest that complement receptors CR1/2, CR3, and CR4 all play important roles in host defense against pneumococcal infection.

J Immunol, 2004 Dec 15, 173(12), 7131 - 4
Cutting edge: expression patterns of surface and soluble triggering receptor expressed on myeloid cells-1 in human endotoxemia; Knapp S et al.; Triggering receptor expressed on myeloid cells-1 (TREM-1) is a recently identified molecule involved in the amplification of inflammation . To determine the regulation of TREM-1, we studied TREM-1 expression and soluble TREM-1 plasma levels upon i.v . LPS challenge in healthy humans in vivo and in vitro . Granulocyte TREM-1 expression was high at baseline and immediately down-regulated upon LPS exposure along with an increase in soluble TREM-1 . Monocytes displayed a gradual up-regulation of TREM-1 upon LPS in vivo and in vitro . In vitro studies extended these findings to highly purified lipoteichoic acid and Streptococcus pneumoniae . Nonbacterial TLR ligands such as polyinosine-polycytidylic acid and imidazoquinoline, as well as the TLR9 ligand CpG, did not impact TREM-1 expression . The LPS-induced alterations in TREM-1 surface expression were not a result of increased TNF-alpha or IL-10 . Inhibitor studies disclosed a PI3K-dependent pathway in LPS-induced up-regulation of TREM-1 on monocytes, whereas MAPK played a limited role.

Pediatr Res . 2004 Dec 7; {Epub ahead of print}
Effects of a Nebulized NONOate, DPTA/NO, on Group B Streptococcus-Induced Pulmonary Hypertension in Newborn Piglets; Dabrowska K et al.; NONOates are chemical compounds that are stable as solids but generate nitric oxide (NO) in aqueous solutions . When nebulized or instilled intratracheally, NONOates can attenuate pulmonary hypertension in adult animals with lung injury . To assess the effect of a nebulized NONOate, DPTA/NO, on group B Streptococcus (GBS)-induced pulmonary hypertension in newborn piglets, we studied 20 anesthetized and mechanically ventilated piglets (4-10 d) . They were randomly assigned to receive nebulized placebo solution or DPTA/NO (100 mg) 15 min after sustained pulmonary hypertension . Pulmonary artery and wedge, systemic, and right atrial pressures; cardiac output; and arterial blood gases were obtained at baseline and every 15 min during 120 min of continuous GBS infusion (6 x 10(8) CFU/min) . Methemoglobin levels were measured at baseline and 60 min . A significant decrease in pulmonary artery pressure, pulmonary vascular resistance (PVR), systemic arterial pressure, and systemic vascular resistance (SVR) was observed after DPTA/NO nebulization (p < 0.001) . Whereas the increase in PVR/SVR observed after GBS infusion was sustained for 120 min in the placebo group, this ratio decreased after DPTA/NO nebulization and remained significantly lower throughout the study period (p < 0.01) . Cardiac output, arterial blood gases, and methemoglobin values did not differ between groups . These data demonstrate that the pulmonary hypertension induced by GBS infusion is markedly attenuated by DPTA/NO nebulization . The lower PVR/SVR observed in the treated group indicates that the vasodilatory effect of NONOate is more pronounced in the pulmonary than systemic vasculature . Therefore, NONOates may have clinical application in the management of pulmonary hypertension secondary to sepsis in neonates.

J Med Microbiol, 2004 Dec, 53(Pt 12), 1241 - 6
Antimicrobial resistance of invasive Streptococcus pneumoniae isolates in a British district general hospital: the international connection; Birtles A et al.; Between January 2000 and March 2001, Streptococcus pneumoniae were isolated from the blood of 56 patients admitted to a single district general hospital in the South-East of England . The serotype and antibiotic susceptibility were determined for all isolates and, for those resistant to erythromycin, the presence or absence of the mef(A) and erm(B) genes was determined by PCR . Multi-locus sequence typing, along with PFGE, was undertaken on all isolates resistant to penicillin or erythromycin and a group of antibiotic-susceptible isolates, to identify whether globally distributed pneumococcal clones, as described by the Pneumococcal Molecular Epidemiology Network (PMEN), were present in the study population . Three serotype 9V penicillin-resistant isolates were identified as belonging to the Spain9V-3 clone, while 14 erythromycin-resistant isolates of serotype 14 belonged to the England14-9 clone . A single multi-resistant isolate of serotype 6B, was found to be a single-locus variant of the Spain6B-2 clone . All 14 erythromycin-resistant serotype 14 isolates possessed the mef(A) gene, while the single multi-resistant isolate possessed the erm(B) gene . These findings confirm the wide distribution and clinical impact of PMEN clones, which accounted for all of the penicillin and erythromycin resistance observed amongst invasive isolates in a district general hospital over a 15-month period.

J Neurochem, 2004 Dec, 91(6), 1450 - 60
Clindamycin is neuroprotective in experimental Streptococcus pneumoniae meningitis compared with ceftriaxone; Bottcher T et al.; In animal models of Streptococcus pneumoniae meningitis, rifampin is neuroprotective in comparison to ceftriaxone . So far it is not clear whether this can be generalized for other protein synthesis-inhibiting antimicrobial agents . We examined the effects of the bactericidal protein synthesis-inhibiting clindamycin (n = 12) on the release of proinflammatory bacterial components, the formation of neurotoxic compounds and neuronal injury compared with the standard therapy with ceftriaxone (n = 12) in a rabbit model of pneumococcal meningitis . Analysis of the CSF and histological evaluation were combined with microdialysis from the hippocampal formation and the neocortex . Compared with ceftriaxone, clindamycin reduced the release of lipoteichoic acids from the bacteria (p = 0.004) into the CSF and the CSF leucocyte count (p = 0.011) . This led to lower extracellular concentrations of hydroxyl radicals (p = 0.034) and glutamate (p = 0.016) in the hippocampal formation and a subsequent reduction of extracellular glycerol levels (p = 0.018) and neuronal apoptosis in the dentate gyrus (p = 0.008) . The present data document beneficial effects of clindamycin compared with ceftriaxone on various parameters linked with the pathophysiology of pneumococcal meningitis and development of neuronal injury . This study suggests neuroprotection to be a group effect of bactericidal protein synthesis-inhibiting antimicrobial agents compared with the standard therapy with beta-lactam antibiotics in meningitis.

Berl Munch Tierarztl Wochenschr, 2004 Nov-Dec, 117(11-12), 459 - 63
Intracellular invasion and persistence: survival strategies of Streptococcus suis and Mycobacterium avium ssp . paratuberculosis; Valentin-Weigand P; Streptococcus (S.) suis and Mycobacterium avium ssp . paratuberculosis (MAP) differ substantially in their host specificity and tissue tropism . S . suis is a facultative pathogen in swine, which mainly colonises the upper respiratory tract and can cause meningitis, septicemia, arthritis and pneumonia . In contrast, MAP is an obligatory pathogen causing paratuberculosis in ruminants, and shows high tropism for the intestinal tract . Both pathogens are able to invade and persist in host cells . In S . suis, the significance of invasion for pathogenesis is a matter of controversial discussions . In vitro it has been shown that S . suis is internalized by epithelial cells and survives intracellularly for at least 24 h . However, at present there is no evidence that S . suis invades epithelial cells also in vivo . In MAP, on the other hand, persistence in macrophages is generally considered a crucial step in pathogenesis, but it remains to be elucidated, how it contributes to pathophysiology of the disease . The two pathogens exemplify how intracellular invasion and persistence might play different roles in pathogenesis . In S . suis, intracellular life may represent only a transient retreat phase, whereas in MAP it is the predominant in vivo niche of the pathogen.

Dis Aquat Organ, 2004 Oct 21, 61(1-2), 67 - 73
Strain variation and geographic endemism in Streptococcus iniae; Kvitt H et al.; Twenty-six Israeli isolates of Streptococcus iniae from both marine and fresh/brackish water sources were compared with each other and with 9 foreign isolates . All the isolates were tentatively identified according to their biochemical profile . Direct sequencing of approximately 600 bp PCR products of the 16S rDNA confirmed their identification as S . iniae at the molecular level and revealed a new (one-nucleotide) variant among Israeli isolates, in addition to 2 variants that had been previously reported . Strain variation was further examined by subjecting the isolates to randomly amplified polymorphic DNA (RAPD) and amplified fragment length polymorphism (AFLP) analyses . The RAPD method allowed separation of the isolates into only 2 groups, one including 5 Israeli fresh/brackish water isolates and one including all the other isolates . The AFLP method grouped the Israeli marine isolates into one homogeneous cluster, although they had been obtained in different years (1995 to 2001) from different species of fish, and from wild (Red Sea) as well as cultured (both Mediterranean and Red Sea) sources . The Israeli fresh/brackish water isolates and foreign isolates separated into distinct entities that clustered at generally high degrees of similarity . The distance between the clusters of the Israeli marine and fresh/brackish water isolates indicates that the S . iniae streptococcosis that has been afflicting the aquaculture industries in the 2 environments in recent years was caused by distinct strains . AFLP showed superior discriminative properties over RAPD in detecting intraspecific variation and proved to be an important tool for the characterization of S . iniae . A correlation between strain variation and geographic endemism was established.

J Clin Microbiol, 2004 Dec, 42(12), 5928 - 30
Detection of resistance to gatifloxacin and moxifloxacin in Streptococcus pneumoniae with the VITEK 2 instrument; Jorgensen JH et al.; A group of 72 pneumococcal isolates resistant or intermediate to levofloxacin and 124 pneumococcal isolates susceptible to fluoroquinolones were tested by the VITEK 2 instrument using investigational test cards and by a broth microdilution reference method . The VITEK 2 instrument performed well, detecting 52 of 60 (86.7%) gatifloxacin-resistant isolates and 22 of 23 moxifloxacin-resistant isolates, and did not falsely classify any susceptible isolates as resistant.

J Clin Microbiol, 2004 Dec, 42(12), 5620 - 3
Prevalence and mechanisms of erythromycin resistance in group A and group B Streptococcus: implications for reporting susceptibility results; Desjardins M et al.; Increased rates of erythromycin resistance among group B Streptococcus (GBS) and group A Streptococcus (GAS) have been reported . Cross-resistance to clindamycin may be present, depending on the mechanism of resistance . We determined the prevalence of macrolide-resistant determinants in GBS and GAS isolates to guide the laboratory reporting of erythromycin and clindamycin susceptibility . Susceptibilities were determined by the disk diffusion and broth microdilution methods . Inducible and constitutive resistance to clindamycin was determined by the double-disk diffusion method . The presence of the ermTR, ermB, and mefA genes was confirmed by PCR . Of the 338 GBS isolates, 55 (17%) were resistant to erythromycin, whereas 26 (8%) were resistant to clindamycin . The erm methylase gene was identified in 48 isolates, 22 of which had inducible resistance to clindamycin and 26 of which had constitutive resistance to clindamycin . The remaining seven resistant isolates had mefA . Of the 593 GAS isolates, 49 (8%) and 6 (1%) isolates were resistant to erythromycin and clindamycin, respectively . Erythromycin resistance was due to mefA in 33 isolates, whereas 14 isolates had erm-mediated resistance (9 isolates had inducible resistance and 5 isolates had constitutive resistance) . In our population, erythromycin resistance in GAS was predominantly mediated by mefA and erythromycin resistance in GBS was predominantly mediated by erm . Regional differences in mechanisms of resistance need to be taken into consideration when deciding whether to report clindamycin susceptibility results on the basis of in vitro test results . Testing by the double-disk diffusion method would be an approach that could be used to address this issue, especially for GAS.

J Clin Microbiol, 2004 Dec, 42(12), 5571 - 7
Trends in antimicrobial resistance in 1,968 invasive Streptococcus pneumoniae strains isolated in Spanish hospitals (2001 to 2003): decreasing penicillin resistance in children's isolates; Oteo J et al.; To address the public health problem of antibiotic resistance, the European Union (EU) founded the European Antimicrobial Resistance Surveillance System . A network of 40 hospitals that serve approximately 30% of the Spanish population (about 12 million) participated . Each laboratory reported data on antimicrobial susceptibility testing using standard laboratory procedures that were evaluated by an external quality control program . The antibiotic consumption data were obtained from the National Health System . We compared the antibiotic susceptibility of Spanish isolates of invasive Streptococcus pneumoniae (2001 to 2003) with antibiotic consumption . Invasive S . pneumoniae was isolated from 1,968 patients, 20% of whom were children at or below the age of 14 years . Of non-penicillin-susceptible strains (35.6%; 95% confidence interval, 34 to 37.2), 26.4% were considered intermediate and 9.2% were considered resistant . Between 2001 and 2003, penicillin resistance decreased from 39.5 to 33% overall and from 60.4 to 41.2% in children at or below the age of 14 years (P = 0.002) . Resistance to erythromycin was at 26.6%, and coresistance with penicillin was at 19.1% . Of total isolates, the ciprofloxacin MIC was >2 mug/ml for 2.1%, with numbers increasing from 0.4% (2001) to 3.9% (2003) . Total antibiotic use decreased from 21.66 to 19.71 defined daily doses/1,000 inhabitants/day between 1998 and 2002 . While consumption of broad-spectrum penicillins, cephalosporins, and erythromycin declined, use of amoxicillin-clavulanate and quinolones increased by 17.5 and 27%, respectively . The frequency of antibiotic resistance in invasive S . pneumoniae in Spain was among the highest in the EU . However, a significant decrease in penicillin resistance was observed in children . This decrease coincided with the introduction of a heptavalent conjugate pneumoccocal vaccine (June 2001) and with a global reduction in antibiotic consumption levels.

J Exp Med, 2004 Dec 6, 200(11), 1383 - 93
SIGN-R1 contributes to protection against lethal pneumococcal infection in mice; Lanoue A et al.; Rapid clearance of pathogens is essential for successful control of pyogenic bacterial infection . Previous experiments have shown that antibody to specific intracellular adhesion molecule-grabbing nonintegrin (SIGN)-R1 inhibits uptake of capsular polysaccharide by marginal zone macrophages, suggesting a role for SIGN-R1 in this process . We now demonstrate that mice lacking SIGN-R1 (a mouse homologue of human dendritic cell-SIGN receptor) are significantly more susceptible to Streptococcus pneumoniae infection and fail to clear S . pneumoniae from the circulation . Marginal zone and peritoneal macrophages show impaired bacterial recognition associated with an inability to bind T-independent type 2 antigens such as dextran . Our work represents the first evidence for a protective in vivo role for a SIGN family molecule.

Biochemistry, 2004 Dec 14, 43(49), 15540 - 9
Enzymatic characterization of the streptococcal endopeptidase, IdeS, reveals that it is a cysteine protease with strict specificity for igg cleavage due to exosite binding; Vincents B et al.; Streptococcus pyogenes, an important pathogen in humans, secretes an IgG specific endopeptidase named IdeS . To elucidate the mechanism that is responsible for this specificity, we have here characterized the activity of IdeS in detail . Both gamma chains of human IgG or its Fc fragment were cleaved in the hinge region after Gly236 by IdeS, but other proteins or synthetic peptides containing sequences such as the P(4)-P(1) segment in the IgG cleavage site, or long peptides resembling the IgG hinge, were not hydrolyzed at all . This is likely due to a second binding site interacting with the Fc part of IgG . The lack of IdeS activity on peptide substrates necessitated the development of an assay with IgG as the substrate for kinetic studies . IdeS showed a sigmoidal velocity curve at physiological IgG concentrations, and a declining enzyme rate at higher IgG concentrations . This atypical velocity curve suggests product inhibition and/or allosteric control, which again indicates the presence of an exosite involved in substrate binding . The pseudoequilibrium constant for IdeS hydrolysis of IgG was 90 microM . The enzyme exhibited activity in the pH range of 5.1-7.6, with an optimum at pH 6.6 . IdeS was stable above pH 10 but not at acidic pH . It exhibited an activity maximum around 37 degrees C and a decreased thermal stability at 42 degrees C . Iodoacetate and iodoacetamide inhibited IdeS, as expected for a cysteine protease, and biochemical evidence verified this classification . E-64 and chicken cystatin, specific inhibitors of family C1 and C13 cysteine proteases, were without effect on enzyme activity, as were class specific serine, aspartic, and metallo protease inhibitors . No significant similarities were found in protein sequence comparisons with known enzyme families, suggesting that IdeS represents a novel family of cysteine proteases.

Ophthalmic Surg Lasers Imaging, 2004 Nov-Dec, 35(6), 503 - 6
Socket infection due to retained gauze after evisceration; Chang YS et al.; A 64-year-old man had late-onset socket infection due to retained surgical gauze after evisceration . External examination showed a mass of retained surgical gauze with copious yellowish discharge and gas bubbles . Computed tomography scans showed a 3.2 x 2.4 x 2.4-cm heterogeneous mass and numerous gas bubbles . Culture of the discharge yielded Pseudomonas aeruginosa, Streptococcus viridans, Peptostreptococcus species, and Fusobacterium species . Surgical debridement and antibiotic therapy achieved a rapid resolution . Retained gauze after evisceration may lead to socket infection, and such a complication should be avoided.

Am J Perinatol, 2004 Nov, 21(8), 491 - 5
Streptococcus pneumoniae: an old bug with significant maternal-newborn implications; Sallam A et al.; Streptococcus pneumoniae is an uncommon organism identified in neonatal bacteremia, but when it occurs, it has serious implications for both the infant and the mother . Despite the similarities in the manifestations between group B streptococcus and S . pneumoniae sepsis, the latter appears to be more virulent and of marked severity, resulting in significant neonatal mortality . In the absence of a routine maternal screening protocol for S . pneumoniae colonization, aggressive newborn management constitutes the mainstay of treatment.

Surg Today, 2004, 34(12), 1053 - 6
Primary peritonitis associated with streptococcal toxic shock-like syndrome: report of a case; Kanetake K et al.; Several reports over the past 15 years describe severe group A streptococcal infections causing septic shock, soft-tissue necrosis, and multiple organ failure; a phenomenon known as streptococcal toxic shock-like syndrome (TSLS) . However, primary peritonitis associated with TSLS is rare . We report the case of a 40-year-old man admitted with pain in both thighs, hypotension, and severe abdominal pain . His daughter had been diagnosed with streptococcal pharyngitis 3 days earlier . We performed an emergency laparotomy for peritonitis, and culture of the ascites was positive for group A beta -hemolytic streptococcus (GAS) . Further serotyping of the isolated GAS strain revealed the T-type 22 and the pyrogenic exotoxin gene, spe-C . The criteria for TSLS were clearly met, including the isolation of GAS from ascites, hypotension, liver failure, renal failure, coagulopathy, myositis, and a generalized erythematous macular rash with desquamation.

J Pediatr Orthop B, 2005 Jan, 14(1), 55 - 60
Osteomyelitis of the rib due to Streptococcus pneumoniae: a very rare condition in children; Kalouche I et al.; Rib osteomyelitis is a rare disease . We present a previously unreported case of Streptococcus pneumoniae osteomyelitis of the rib . A 4-month-old-infant presented with fever, irritability and abdominal tenderness . Pericostal collection was discovered incidentally on ultrasound; it was first drained by needle aspiration and appropriate antibiotic therapy was given, with resolution of fever in 24 h, but recurrence of symptoms 4 days later, with swelling over the affected rib . Surgical drainage with resection of the infected portion of the rib were done followed by a prolonged course of intravenous and then oral antibiotics, without any recurrence at 6 months follow-up . A review of the pertinent literature was made . This case demonstrates that the spectrum of pathogens potentially responsible for rib osteomyelitis may be broader than previously reported . The management and outcome are similar to rib osteomyelitis due to any other bacteria.

J Bacteriol, 2004 Dec, 186(24), 8524 - 8
The F-ATPase operon promoter of Streptococcus mutans is transcriptionally regulated in response to external pH; Kuhnert WL et al.; Streptococcus mutans F-ATPase, the major component of the acid-adaptive response of the organism, is transcriptionally upregulated at low pH . Fusions of the F-ATPase promoter to chloramphenicol acetyltransferase indicated that pH-dependent expression is still observed with a short promoter that contains a domain conserved between streptococcal ATPase operons.

J Bacteriol, 2004 Dec, 186(24), 8463 - 71
Revising the role of the pneumococcal vex-vncRS locus in vancomycin tolerance; Haas W et al.; Vancomycin is used increasingly to treat invasive infections caused by multidrug-resistant Streptococcus pneumoniae . Although no vancomycin-resistant strains have been isolated to date, tolerant strains that fail to die rapidly and that cause relapsing disease have been described . The vex123-pep27-vncRS locus, consisting of an ABC transporter, a presumed signaling peptide, and a two-component system, respectively, has been implicated in vancomycin tolerance . Recent findings, however, challenged this model . The data presented here indicate that erythromycin in the growth medium induces a vancomycin-tolerant phenotype and that loss of function of Pep27 or VncRS does not alter autolysis . However, a role for the ABC transporter encoded by the vex123 genes in tolerance was confirmed . A vex3 mutant was considerably more tolerant to vancomycin treatment than the wild-type strain T4, and the strength of the phenotype depended on the orientation of the resistance cassette used to construct the mutant . Microarray results suggested a number of genes that might be involved in tolerance in the vex3 mutant . Although the exact function and regulation of the vex123-pep27-vncRS locus remains to be determined, several factors influence the autolysis behavior of S . pneumoniae, including the bacterial capsule, erythromycin, and the lytA and vex3 gene products.

J Bacteriol, 2004 Dec, 186(24), 8229 - 39
Characterization of LytA-like N-acetylmuramoyl-L-alanine amidases from two new Streptococcus mitis bacteriophages provides insights into the properties of the major pneumococcal autolysin; Romero P et al.; Two new temperate bacteriophages exhibiting a Myoviridae (phiB6) and a Siphoviridae (phiHER) morphology have been isolated from Streptococcus mitis strains B6 and HER 1055, respectively, and partially characterized . The lytic phage genes were overexpressed in Escherichia coli, and their encoded proteins were purified . The lytAHER and lytAB6 genes are very similar (87% identity) and appeared to belong to the group of the so-called typical LytA amidases (atypical LytA displays a characteristic two-amino-acid deletion signature) . although they exhibited several differential biochemical properties with respect to the pneumococcal LytA, e.g., they were inhibited in vitro by sodium deoxycholate and showed a more acidic pH for optimal activity . However, and in sharp contrast with the pneumococcal LytA, a short dialysis of LytAHER or LytAB6 resulted in reversible deconversion to the low-activity state (E-form) of the fully active phage amidases (C-form) . Comparison of the amino acid sequences of LytAHER and LytAB6 with that of the pneumococcal amidase suggested that Val317 might be responsible for at least some of the peculiar properties of S . mitis phage enzymes . Site-directed mutagenesis that changed Val317 in the pneumococcal LytA amidase to a Thr residue (characteristic of LytAB6 and LytAHER) produced a fully active pneumococcal enzyme that differs from the parental one only in that the mutant amidase can reversibly recover the low-activity E-form upon dialysis . This is the first report showing that a single amino acid residue is involved in the conversion process of the major S . pneumoniae autolysin . Our results also showed that some lysogenic S . mitis strains possess a lytA-like gene, something that was previously thought to be exclusive to Streptococcus pneumoniae . Moreover, the newly discovered phage lysins constitute a missing link between the typical and atypical pneumococcal amidases known previously.

J Bacteriol, 2004 Dec, 186(24), 8181 - 92
Evolutionary genetics of the capsular locus of serogroup 6 pneumococci; Mavroidi A et al.; The evolution of the capsular biosynthetic (cps) locus of serogroup 6 Streptococcus pneumoniae was investigated by analyzing sequence variation within three serotype-specific cps genes from 102 serotype 6A and 6B isolates . Sequence variation within these cps genes was related to the genetic relatedness of the isolates, determined by multilocus sequence typing, and to the inferred patterns of recent evolutionary descent, explored using the eBURST algorithm . The serotype-specific cps genes had a low percent G+C, and there was a low level of sequence diversity in this region among serotype 6A and 6B isolates . There was also little sequence divergence between these serotypes, suggesting a single introduction of an ancestral cps sequence, followed by slight divergence to create serotypes 6A and 6B . A minority of serotype 6B isolates had cps sequences (class 2 sequences) that were approximately 5% divergent from those of other serotype 6B isolates (class 1 sequences) and which may have arisen by a second, more recent introduction from a related but distinct source . Expression of a serotype 6A or 6B capsule correlated perfectly with a single nonsynonymous polymorphism within wciP, the rhamnosyl transferase gene . In addition to ample evidence of the horizontal transfer of the serotype 6A and 6B cps locus into unrelated lineages, there was evidence for relatively frequent changes from serotype 6A to 6B, and vice versa, among very closely related isolates and examples of recent recombinational events between class 1 and 2 cps serogroup 6 sequences.

J Bacteriol, 2004 Dec, 186(24), 8164 - 71
Pyruvate oxidase is a determinant of Avery's rough morphology; Belanger AE et al.; In pioneering studies, Avery et al . identified DNA as the hereditary material (A . T . Avery, C . M . MacLeod, and M . McCarty, J . Exp . Med . 79:137-158, 1944) . They demonstrated, by means of variation in colony morphology, that this substance could transform their rough type 2 Streptococcus pneumoniae strain R36A into a smooth type 3 strain . It has become accepted as fact, from modern textbook accounts of these experiments, that smooth pneumococci make capsule, while rough strains do not . We found that rough-to-smooth morphology conversion did not occur in rough strains R36A and R6 when the ability to synthesize native type 2 capsule was restored . The continued rough morphology of these encapsulated strains was attributed to a second, since-forgotten, morphology-affecting mutation that was sustained by R36A during strain development . We used a new genome-PCR-based approach to identify spxB, the gene encoding pyruvate oxidase, as the mutated locus in R36A and R6 that, with unencapsulation, gives rise to rough colony morphology, as we know it . The variant spxB allele of R36A and R6 is associated with increased cellular pyruvate oxidase activity relative to the ancestral strain D39 . Increased pyruvate oxidase activity alters colony shape by mediating cell death . R36A requires a wild-type spxB allele for the expression of smooth type 2 morphology but not for the expression of smooth type 3 morphology, the phenotype monitored by Avery et al . Thus, the mutated spxB allele did not impact their use of smooth morphology to identify the transforming principle.

J Perinat Med, 2004, 32(6), 535 - 7
Prolonged fetal bradycardia as the presenting clinical sign in Streptococcus agalactiae chorioamnionitis; Presta G et al.; Group B Streptococcus remains a leading infectious cause of neonatal morbidity and mortality . We report a case of a 37 weeks' gestation infant with severe birth asphyxia, status epilepticus and GBS chorioamnionitis, in which a prolonged fetal bradycardia was the only prenatal clinical sign.

Vaccine, 2004 Dec 6, 22 Suppl 1, S9 - S14
Host-pathogen interactions in Streptococcus pyogenes infections, with special reference to puerperal fever and a comment on vaccine development; Areschoug T et al.; Streptococcus pyogenes (group A streptococcus) causes a variety of diseases, including acute pharyngitis, impetigo, rheumatic fever and the streptococcal toxic shock syndrome . Moreover, S . pyogenes was responsible for the classical example of a nosocomial infection, the epidemics of puerperal fever (childbed fever) that caused the death of numerous women in earlier centuries . The most extensively studied virulence factor of S . pyogenes is the surface M protein, which inhibits phagocytosis and shows antigenic variation . Recent data indicate that many M proteins confer phagocytosis resistance because the variable N-terminal region has non-overlapping sites that specifically bind two components of the human immune system, the complement inhibitor C4b-binding protein (C4BP) and IgA-Fc . Concerning puerperal fever, molecular and epidemiological analysis suggests that the S . pyogenes surface protein R28 may have played a pathogenetic role in these epidemics . This article summarizes the properties of M protein and the R28 protein and considers a potential problem encountered in connection with the use of animal models for vaccine development.

J Am Soc Nephrol, 2005 Jan, 16(1), 247 - 54 Epub 2004 Dec 01.
Glomerular plasmin-like activity in relation to nephritis-associated plasmin receptor in acute poststreptococcal glomerulonephritis; Oda T et al.; A nephritogenic antigen for acute poststreptococcal glomerulonephritis (APSGN) was isolated recently from group A streptococcus and termed nephritis-associated plasmin receptor (NAPlr) . In vitro experimental data indicate that the pathogenic role of NAPlr occurs through its ability to bind to plasmin and maintain its proteolytic activity . However, the mechanism whereby this antigen induces glomerular damage in vivo has not been fully elucidated . Renal biopsy tissues from 17 patients with APSGN, 8 patients with rapidly progressive glomerulonephritis, and 10 normal kidneys were analyzed in this study . Plasmin-like activity was assessed on cryostat sections by in situ zymography with a plasmin-sensitive synthetic substrate . Serial sections were simultaneously assessed for NAPlr deposition by immunofluorescence staining . Glomerular plasmin-like activity was absent or weak in normal controls and in patients with rapidly progressive glomerulonephritis, although tubulointerstitial activity was occasionally detected . Prominent glomerular plasmin-like activity was found in patients who had APSGN and in whom glomerular NAPlr was positive, whereas it was absent or weak in patients who had APSGN and in whom glomerular NAPlr was negative . The distribution of glomerular plasmin-like activity was identical to that of NAPlr deposition but was generally different from that of fibrin(ogen) deposition as assessed by double staining . The activity was abolished by the addition of aprotinin to the reaction mixture but was not altered by the addition of a matrix metalloprotease inhibitor, a cysteine protease inhibitor, or inhibitors of plasminogen activators . Thus, upregulated glomerular plasmin-like activity in relation to NAPlr deposition in APSGN was identified . This result supports the nephritogenic character of NAPlr and offers insight into the mechanism whereby this antigen induces nephritis.

Proc Natl Acad Sci U S A, 2004 Dec 14, 101(50), 17371 - 6 Epub 2004 Dec 01.
Structure of the streptococcal endopeptidase IdeS, a cysteine proteinase with strict specificity for IgG; Wenig K et al.; Pathogenic bacteria have developed complex and diverse virulence mechanisms that weaken or disable the host immune defense system . IdeS (IgG-degrading enzyme of Streptococcus pyogenes) is a secreted cysteine endopeptidase from the human pathogen S . pyogenes with an extraordinarily high degree of substrate specificity, catalyzing a single proteolytic cleavage at the lower hinge of human IgG . This proteolytic degradation promotes inhibition of opsonophagocytosis and interferes with the killing of group A Streptococcus . We have determined the crystal structure of the catalytically inactive mutant IdeS-C94S by x-ray crystallography at 1.9-A resolution . Despite negligible sequence homology to known proteinases, the core of the structure resembles the canonical papain fold although with major insertions and a distinct substrate-binding site . Therefore IdeS belongs to a unique family within the CA clan of cysteine proteinases . Based on analogy with inhibitor complexes of papain-like proteinases, we propose a model for substrate binding by IdeS.

Arch Bronconeumol, 2004 Dec, 40(12), 599 - 601
Diffuse Thoracic Lymphangiomatosis: Diagnosis and Treatment; Bermejo Casero EJ et al.; Histologically, lymphangiomatosis is a rare type of benign neoplasm caused by abnormal development and proliferation of the lymphatic system . Thoracic lymphangiomatosis can present in a localized (lymphangioma) or diffuse form (lymp-hangiomatosis) . In most cases the disease progresses to serious morbidity or even death . The treatment of choice for localized disease is usually surgery or, less frequently, local injection of sclerosing agents (streptococcus antigen OK-432) . However, in diffuse forms there is a gelatinous infiltrate without defined limits . In these cases the main treatment option is radiotherapy . We report 2 cases of diffuse thoracic lymphangiomatosis with pulmonary infiltrate . In both cases radiotherapy in appropriate doses successfully eliminated pulmonary infiltrates, pleural effusion, dyspnea, and general discomfort . Surgery was needed to resolve complications of the disease and for diagnosis.

An Pediatr (Barc), 2004 Dec, 61(6), 554 - 7
{Primary peritonitis in previously healthy children.}; Navia MJ et al.; Introduction: Primary peritonitis occurs rarely in childhood, affecting mainly children with nephrosis or liver disease and only rarely occurring in previously healthy children . The aim of this case report is to describe the clinical features and natural course of primary peritonitis in six previously healthy children and to review the literature on the topic . Material and method: The clinical features and course of primary peritonitis in six previously healthy children are described . The diagnosis was made at laparotomy, which showed no intraabdominal findings, such as intestinal perforation . Results: Presentation was acute and all the patients presented within 24 h of onset of symptoms . The most common presenting features were fever (100 %) and abdominal pain (100 %) . Leucocytosis (> 15,000/mm3) was observed in four patients (66 %) . Microorganisms were isolated from peritoneal fluid in four patients (Escherichia coli in two, Streptococcus pneumoniae in one and Gram-negative bacteria in one) . Recovery was rapid and no postoperative complications were observed . Conclusion: Primary peritonitis in patients without underlying causes is clinically indistinguishable from acute appendicitis and diagnosis is usually made at surgery . The hallmarks of therapy are antibiotics and prompt exploratory laparotomy with appendectomy and the prognosis is good.

Biochem J . 2004 Dec 2; {Epub ahead of print}
Accumulation of partly folded states in the equilibrium unfolding of the pneumococcal choline-binding module C-LytA; Maestro B et al.; Choline-binding modules are present in some virulence factors and many other proteins of Streptococcus pneumoniae (pneumococcus) . The most extensively studied choline-binding domain is C-LytA, the carboxy-terminal moiety of the pneumococcal cell-wall amidase LytA . The three-dimensional structure of C-LytA is built up from six loop-hairpin structures forming a left-handed beta-solenoid with four choline binding sites . The affinity of C-LytA for choline and other structural analogues allows its use as an efficient fusion tag for single-step purification of hybrid proteins . Here we characterize the folding and stability of C-LytA by chemical and thermal equilibrium denaturation experiments . Unfolding experiments using guanidinium chloride at pH 7.0 and 20 oC suggest the existence of two partly folded states (I 1 and I 2) in the following model: N (native) -> I 1 <=> I 2 . The N -> I 1 transition is non-cooperative and irreversible, and is significant even in the absence of denaturant . In contrast, the I 1 <=> I 2 2 transition is cooperative and reversible, with an associated free energy change (DeltaG o) of 30.9 +/- 0.8 kcal mol -1 . The residual structure in the I 2 state is unusually stable even in 7.4 M guanidinium chloride . Binding of choline stabilizes the structure of the native state, induces its dimerization and prevents the accumulation of the I 1 species ({N} 2 <=> {I 2} 2, DeltaG o = 50.1 +/- 0.8 kcal mol -1 . Fluorescence and circular dichroism measurements, gel filtration chromatography and limited proteolysis suggest that I 1 differs from N in the local unfolding of the N-terminal beta-hairpins, and that I 2 has residual structure in the C-terminal region . Thermal denaturation of C-LytA suggests the accumulation of at least the I 1 species . These results might pave the way for an effective improvement of its biotechnological applications by protein engineering.

J Indian Soc Pedod Prev Dent, 2004 Sep, 22(3), 100 - 5
Evaluation of an alum-containing mouthrinse for inhibition of salivary streptococcus mutans levels in children--a controlled clinical trial; Mourughan K et al.; The anticariogenic effect of alum was evaluated in the study by measuring the salivary S . mutans levels of children at baseline, after 3-weeks, and 6-weeks of using alum-containing mouthrinses . Sixty subjects with a mean age of eleven years were selected and randomly divided into four groups . Two experimental mouthrinses (alum in physiological saline and alum in distilled water) and two control mouthrinses (physiological saline and distilled water) were given for a period of 6 weeks on a daily basis . Salivary samples were collected at the end of 3 weeks and 6 weeks and S . mutans levels were assessed and compared with baseline values and among each other . Both the alum-containing mouthrinses produced statistically significant reductions in S . mutans levels in children, thus tempting us to announce alum as a routine oral hygiene measure, though its safety for prolonged usage needs to be established by long-term studies.

Rev Neurol, 2004 Nov 16-30, 39(10), 935 - 9
{Mondini dysplasia: recurrent bacterial meningitis in adolescence}; Vargas-Diaz J et al.; INTRODUCTION: Episodes of recurrent bacterial meningitis can occur in patients due to either congenital or acquired disorders . Congenital deformity of the bony labyrinth can be linked to a fistulous tract communicating it with the intracranial subarachnoid space . Mondini deformity is a frequent malformation in congenitally deaf patients . CASE REPORT: We report the case of an adolescent with a history of being unable to hear in one ear who, from the age of 10 years, began to suffer repeated bacterial meningoencephalitis with microbiological recovery of Streptococcus pneumoniae on three occasions . The type of germ recovered in the cerebrospinal fluid (CSF) and the history of congenital deafness that was detected when the patient was 3 years old were the diagnostic clues to the possible anomaly of the inner ear with a CSF fistula . The clinically proven CSF rhinorrhea contributed to the diagnosis of an ear anomaly with a fistula . Computerised axial tomography and magnetic resonance studies of the petrous portion of the temporal bone revealed the malformation that was later found and closed during the surgical intervention on the affected ear . The clinical absence of rhinorrhea, a year's progression without new infections after operating on the patient and post-surgery imaging studies were all proof that the fistula had closed . CONCLUSIONS: Mondini dysplasia with CSF fistula must be included as a possible diagnosis when faced with a patient with recurrent bacterial meningoencephalitis . Imaging studies, especially magnetic resonance, enable the clinician to check the diagnosis and the CSF fistula can be closed with ear surgery.

Biophys Chem, 2004 Dec 20, 112(2-3), 201 - 7
Actions of the functional upstream domain of protein F1 of Streptococcus pyogenes on the conformation of fibronectin; Ensenberger MG et al.; Fibronectin (Fn), discovered by Harvard's Plasma Protein Program as plasma "cold-insoluble globulin" in the 1940s, has attracted much interest over the past three decades . One of the most interesting features of Fn is its ability to change shape in response to various environmental conditions and interactions with other substances found in the extra-cellular space . Here we examine the potential of the functional upstream domain (FUD) of Streptococcus pyogenes protein F1 to bring about changes in structure of Fn . In particular, we investigate the accessibility of Fn's 10th type III module that contains the integrin binding RGD motif . By use of monoclonal antibodies in a competitive ELISA assay, we found that FUD interacts with the amino-terminal type I modules of Fn to unveil the cell-binding region of Fn . This conformational change was achieved at sub-equimolar ratios of FUD/Fn monomer . We discuss the functional relevance of the interaction for both Fn and S . pyogenes and correlate the results with a conformational model of Fn that arose out of a collaboration between our laboratory and that of John Ferry.

Anal Chem, 2004 Dec 1, 76(23), 6887 - 93
Enzymatic genosensor on streptavidin-modified screen-printed carbon electrodes; Hernandez-Santos D et al.; Voltammetric enzyme genosensors on streptavidin-modified screen-printed carbon electrodes (SPCEs) for the detection of virulence nucleic acid determinants of pneumolysin and autolysin genes, exclusively present on the genome of the human pathogen Streptococcus pneumoniae, were described . Alkaline phosphatase (AP) and 3-indoxyl phosphate were used as the enzymatic label and substrate, respectively . The oligonucleotide probes were immobilized on electrochemically pretreated SPCEs through the streptavidin/biotin reaction . The adsorption of streptavidin was performed by deposition of a drop of a streptavidin solution overnight at 4 degrees C on the surface of the SPCEs . After the hybridization reaction with FITC-labeled complementary targets, the enzyme is captured using an anti-FITC antibody conjugated to AP . In nonstringent experimental conditions, these genosensors can detect 0.49 fmol of 20-mer oligonucleotide target and discriminate between a complementary oligo and an oligo with a three-base mismatch . In the presence of 25% formamide in the hybridization buffer, a single-base mismatch on the oligonucleotide target can be detected.

Clin Nephrol, 2004 Nov, 62(5), 391 - 6
Group B Streptococcus (Streptococcus agalactiae) peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD); Liakopoulos V et al.; Streptococcus agalactiae typically induces serious infections in pregnant women and newborns . Nonpregnant adult patients can also be infected and mortality rate exceeds 40% . CAPD peritonitis is very rarely induced by S . agalactiae . Seven cases have been described previously and all had a very severe course, which included bacteremia, septic shock and death . A 27-year-old male with end-stage renal disease due to membranoprolipherative glomerulonephritis type I, who was on CAPD for 17 months, was admitted with the clinical and laboratory picture of CAPD peritonitis . Severe abdominal pain, shaking chills and fever 38.5 microC were also observed at presentation . Streptococcus agalactiae was isolated from the peritoneal fluid and blood culture was sterile . Under treatment with ceftazidime and tobramycin (i.p.) and vancomycin (i.v.) cultures became negative after 48 hours, abdominal symptoms resolved after 12 days and WBC count in the dialysate normalized after 14 days . As a possible source of infection the patient's partner was shown to be a vaginal carrier of a clone of S . agalactiae identical to that isolated in the peritoneal fluid . S . agalactiae is a rare cause of CAPD peritonitis with potentially very serious consequences . Anal or genital tract colonization is, in general, the source of contamination with S . agalactiae . The microbiological findings in the case presented here suggest that colonization of the patient or of his close environment may be important in the pathogenesis of S . agalactiae-induced CAPD peritonitis.

Gan To Kagaku Ryoho, 2004 Nov, 31(12), 2011 - 5
{Infection control in neutropenia induced by high-dose cytarabine chemotherapy}; Miyazaki M et al.; A high-dose cytarabine (Cylocide; Ara-C: HDAC) chemotherapy has been successfully used as a postremission consolidation therapy for acute myeloid leukemia (AML) . Although this chemotherapy has been estimated to cause severe myelosuppression, there has been no report about infection risk relating to HDAC chemotherapy . The purpose of this retrospective study is to evaluate the infection risk in AML patients treated with HDAC (n = 18) compared to those treated with standard-dose Ara-C (SDAC, n = 18) . The mean duration of severe neutropenia (neutrophils < 500/microl) in HDAC group and SDAC was 14.8 days and 10.4 days, respectively, indicating a significant prolongation in the HDAC group (p < 0.05) . The frequency of febrile neutropenia in the HDAC group tended to increase compared to that in the SDAC group (p = 0.093) . The average days of usage of quinolone antimicrobial prophylaxis and aminoglycoside antibiotic injection in febrile neutropenia in the HDAC group were significantly longer than those of the SDAC group (quinolone; p < 0.01, aminoglycoside; p < 0.05) . The frequency of Streptococcus infection isolated from pharyngeal mucus in the HDAC group was significantly higher than that in the SDAC group (100% versus 75%; p < 0.05) . These results suggest that HDAC chemotherapy increased the infection risk compared to SDAC, and especially patients who received HDAC need a further prevention plan against gram-positive bacteria.

J Biomed Opt, 2004 Nov-Dec, 9(6), 1182 - 6
Measurement of bacterial concentration fractions in polymicrobial mixtures by Raman microspectroscopy; Zhu Q et al.; Relative concentrations of Streptococcus mutans and Streptococcus sanguis are important parameters in the study of dental caries, but current methods of measuring these concentrations are time consuming and prone to inaccuracies . We investigate the use of Raman spectroscopy for measuring relative concentrations of these two bacterial species in solid mixtures . To our knowledge, this is the first time Raman spectroscopy has been used to analyze bacterial mixtures rather than to identify the species of a pure colony . Mixtures of the two streptococcal species in various ratios are measured for 200 s using a home-built Raman microscope . Spectral correlations with bacterial content were identified via partial least-squares analysis . The relative concentrations of S . mutans in subsequent samples are predicted with a root mean squared error below 5% . In clinical plaque samples, this sort of accuracy would enable discrimination between normal and dangerously elevated levels of S . mutans . Samples with and without salivary proteins are predicted with equal accuracy . This result shows the potential of Raman spectroscopy for analyzing mixed populations of bacteria, such as those that occur in oral plaques .

Expert Rev Anti Infect Ther, 2004 Dec, 2(6), 831 - 43
Gemifloxacin: a new, potent fluoroquinolone for the therapy of lower respiratory tract infections; File TM Jr et al.; The fluoroquinolone gemifloxacin has recently been approved for the treatment of acute bacterial exacerbations of chronic bronchitis and mild community acquired pneumonia, including that caused by multidrug-resistant Streptococcus pneumoniae . Owing to the increasing prevalence of multidrug-resistant S . pneumoniae, as well as resistance to other common pathogens of acute bacterial exacerbations of chronic bronchitis and community acquired pneumonia, it is important to have new, potent antimicrobial agents for the treatment of these infections . Gemifloxacin is the most potent antimicrobial agent in vitro for S . pneumoniae, and has excellent activity against the other key pathogens of acute bacterial exacerbations of chronic bronchitis and community acquired pneumonia, including the atypical microorganisms . The clinical trial outcomes of several studies that have evaluated gemifloxacin show a range of superior clinical or bacteriologic outcomes against several current antimicrobials, including levofloxacin, clarithromycin, trovafloxacin and ceftriaxone . The safety profile of gemifloxacin is similar to that of approved agents to treat acute bacterial exacerbations of chronic bronchitis and community acquired pneumonia, with a low discontinuation rate of 2.2% . A nonphototoxic rash (usually a mild, maculopapular rash) was observed in 2.8% of patients in clinical studies.

Afr J Med Med Sci, 2004 Jun, 33(2), 131 - 4
Effects of different brands of fluoride dentifrices on dental caries incidence in the rat; Akande OO et al.; The effectiveness of 3 different brands of fluoride-containing dentifrices on the prevention of dental caries was investigated in molars of young rats . Forty albino Wistar rats weighing 50-80g, 28 males and 12 females were inoculated in the mouth with streptococcus viridans daily from day 1 to day 5 of the experiment . The animals were then divided into four groups and fed with rat pellets containing 60% sucrose added as granulated sugar . All the groups were given water ad libitum . Group I had daily tooth brushing with water and served as the control while groups II, III and IV received daily brushing of their molar teeth with different fluoride--containing dentifrices: (Maxam, Florish and Close-Up respectively . All topical treatments were given for one minute daily per rat from day 6 to day 56 of the experiment . At the end of the experiment the animals were sacrificed, the jaws removed and the teeth were scored for occlusal caries . All fluoride--containing dentifrices tested reduced caries in the following order: Maxam 37.86%, Florish 59.22% and Close-Up 57.28% . This study confirmed that fluoride incorporated in Florish and Close-Up showed significant levels of caries reduction (P <0.01) and (P <0.05) respectively in the rat . It also adds credence to Dental Health Education in the application of various tooth pastes in oral hygiene measures.

J Chemother, 2004 Oct, 16(5), 419 - 36
Future trends in antimicrobial chemotherapy: expert opinion on the 43rd ICAAC; Ball AP et al.; The current document bestows an expert synopsis of key new information presented at the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) meeting in 2003 . Data is presented on the socio-political aspects of and policies on antimicrobial prescribing, novel mechanisms of resistance in Streptococcus pneumoniae, and current epidemiological trends in global resistance . Novel information on new (and existing) antimicrobial agents--new penicillins, cephalosporins, monobactams and oxipenem inhibitors, ketolides, glycopeptides, fluoroquinolones (and hybrids), peptides, daptomycin, aminomethylcyclines, glycylcyclines, and newer formulations of agents such as amoxycillin-clavulanate--provides renewed hope that resistant pathogens can be controlled through use of more potent agents . Improved strategies for the use of existing antimicrobial agents, such as the use of high-dose regimens, short-course therapy, also may delay or reduce the development of resistance and preserve the value of our antibiotic armamentarium.

Vet Microbiol, 2004 Dec 9, 104(3-4), 179 - 88
Identification of a novel collagen-like protein, SclC, in Streptococcus equi using signal sequence phage display; Karlstrom A et al.; Strangles is a serious disease in horses caused by Streptococcus equi subspecies equi . In this study, genes encoding putative extracellular proteins in this subspecies have been identified using signal sequence phage display . Among these, one showed similarities to the SclB protein, a member of the collagen-like proteins of Streptococcus pyogenes . The novel gene denoted sclC encodes a protein, SclC, of 302 amino acids, containing typical features found in cell wall-anchored proteins in Gram-positive bacteria . Based on similarities to the S . pyogenes collagen-like proteins the mature SclC protein can be divided into various domains: an N-terminal non-repetitive region (A), a highly repetitive collagen-like region (CL), and a C-terminal proline-rich wall-associated region (W) . Using PCR, the sclC gene was detected in all studied strains of S . equi subsp . equi and S . equi subsp . zooepidemicus . Further, antibodies against recombinant SclC were detected in a collection of sera from horses with no history of strangles as well as horses previously infected with S . equi subsp . equi . Interestingly, the sera from convalescence horses were found to have significantly increased antibody titers against the SclC protein indicating that this protein is expressed during infection of S . equi subsp . equi.

J Antimicrob Chemother, 2004 Dec, 54(6), 991 - 8 Epub 2004 Nov 24.
Distribution and molecular analysis of mef(A)-containing elements in tetracycline-susceptible and -resistant Streptococcus pyogenes clinical isolates with efflux-mediated erythromycin resistance; Brenciani A et al.; OBJECTIVES: To analyse the distribution and molecular features of mef(A)-containing elements in a large collection of different Streptococcus pyogenes clinical isolates with efflux-mediated erythromycin resistance . To further characterize a tet(O)-mef(A) element . METHODS: Gene detection was carried out by PCR using primers designed from established sequences or from sequences in this study . From a tet(O)-mef(A) element ( approximately 60 kb), an 11 972 bp region including the tet(O) and mef(A) genes was sequenced . RESULTS: In the tetracycline-susceptible isolates (n =28), the mef(A) gene was contained in a regular Tn1207.1 transposon (7.2 kb), which was inserted into one of two previously described elements, Tn1207.3 ( approximately 52 kb) or a 58.8 kb chimeric element, both flanked by the comEC gene . In the tetracycline-resistant isolates (n =61), all of which carried the tet(O) gene, the mef(A) gene was part of a variable Tn1207.1-related transposon inserted into unique elements which contained the tet(O) gene approximately 2.3 to 5.5 kb upstream of the mef(A) gene and were not flanked by the comEC gene . In the Tn1207.1-like transposon of these tet(O)-mef(A) elements, only msr(D) (orf5) and a modified orf6, in addition to mef(A), were detected by PCR in all isolates tested; while orf1 and orf2 were always undetectable, orf3, orf7 and orf8 were found in variable percentages . In an orf3-positive element, sequencing identified four new open reading frames downstream of the tet(O) gene, followed by three short sequences with homology to sequences of the pneumococcal mega element . CONCLUSIONS: The mef(A) gene is carried on different chromosomal genetic elements depending on whether the isolates are susceptible or resistant to tetracycline.

J Antimicrob Chemother, 2004 Dec, 54(6), 1062 - 6 Epub 2004 Nov 24.
Pharmacodynamic studies of amoxicillin against Streptococcus pneumoniae: comparison of a new pharmacokinetically enhanced formulation (2000 mg twice daily) with standard dosage regimens; Odenholt I et al.; OBJECTIVES: To compare the pharmacodynamic effects of a pharmacokinetically enhanced formulation of amoxicillin 2000 mg twice daily, with amoxicillin 875 mg twice daily, 875 mg three times daily and 500 mg three times daily against Streptococcus pneumoniae with different susceptibility to amoxicillin in an in vitro kinetic model . METHODS: Strains of S . pneumoniae with amoxicillin MICs of 1, 2, 4 and 8 mg/L at an initial inoculum of approximately 10(5) cfu/mL were exposed to amoxicillin in an in vitro kinetic model simulating the human serum concentration-time profile of the pharmacokinetically enhanced formulation twice daily (C(max) 17 mg/L after 1.5 h) . All isolates were also exposed to amoxicillin with concentration-time profiles correlating to the human dosage of 875 mg twice daily (C(max) 15 mg/L after 1 h), 875 mg three times daily and 500 mg (C(max) 8 mg/L after 1 h) three times daily with simulated half-life of 1 h . Repeated samples were taken regularly during 24 h and viable counts were carried out . RESULTS: Overall, the pharmacokinetically enhanced formulation was more effective at reducing bacterial counts than any of the other formulations evaluated . Eradication was achieved with the enhanced formulation for strains with a MIC of </=2 mg/L, however, regrowth occurred with the other dosing regimens . In the experiments with the strain with a MIC of 4 mg/L, the enhanced formulation kept the bacterial counts </=10(2) cfu/mL for at least 14 out of 24 h tested . In contrast, none of the other formulations reduced the bacterial counts down to </=10(2) cfu/mL at any point . None of the regimens was able to eradicate the strain with an MIC of 8 mg/L, even though an initial substantial kill was noted with the enhanced formulation after both doses . The least effective dosage regimen for all strains was 875 mg twice daily.

J Periodontol, 2004 Oct, 75(10), 1327 - 34
Efficacy of antibiotics against periodontopathogenic bacteria within epithelial cells: an in vitro study; Eick S et al.; BACKGROUND: Periodontopathogenic bacteria can invade and survive within epithelial cells, but susceptibility of intracellular infection to antibiotics used in periodontitis treatment has not been studied to date . METHODS: KB cells were infected by Actinobacillus actinomycetemcomitans, strain NCTC 9710; Porphyromonas gingivalis, strains ATCC 33277 and JH16-1; or Streptococcus constellatus, strain J012b . After 2, 4, and 12 hours the bactericidal effect of antibiotics (clindamycin, doxycycline, metronidazole, and moxifloxacin) on intracellular microorganisms was tested at a concentration up to the 100-fold minimum inhibitory concentration (MIC) determined separately on planktonic bacteria . RESULTS: The P . gingivalis strains differed in their invasiveness and ATCC 33277 was 100-fold more invasive than JH16-1 . Doxycycline and clindamycin at a concentration 10-fold MIC had no effect, but P . gingivalis intercellular infection was significantly reduced by metronidazole at 10-fold MIC after 2 and 4 hours . Moxifloxacin was effective, but a 100-fold MIC concentration was necessary to reduce P . gingivalis strains intracellular growth to 7% of the control . Other bacterial species grown inside the KB cells were more susceptible to antibiotics . Clindamycin at 10-fold MIC reduced the number of intracellular S . constellatus after 4 and 12 hours . This bacterium was eliminated by moxifloxacin at 50-fold MIC . Intracellular A . actinomycetemcomitans was killed by 10-fold MIC of doxycycline and moxifloxacin after 4 hours incubation . CONCLUSIONS: Moxifloxacin was the most efficient antibiotic to treat intracellular infection . However, taking into account the MIC values and the levels of antibiotics in gingival fluid, elimination of intracellular bacteria by antibiotics alone seems to be questionable.

Antimicrob Agents Chemother, 2004 Dec, 48(12), 4725 - 32
Antibacterial activity of a competence-stimulating peptide in experimental sepsis caused by Streptococcus pneumoniae; Oggioni MR et al.; Streptococcus pneumoniae, a major cause of human disease, produces a 17-mer autoinducer peptide pheromone (competence-stimulating peptide {CSP}) for the control of competence for genetic transformation . Due to previous work linking CSP to stress phenotypes, we set up an in vivo sepsis model to assay its effect on virulence . Our data demonstrate a significant increase in the rates of survival of mice, reductions of blood S . pneumoniae counts, and prolonged times to death for mice treated with CSP . In vitro the dose of CSP used in the animal model produced a transitory inhibition of growth . When a mutant with a mutation in the CSP sensor histidine kinase was assayed, no bacteriostatic phenotype was detected in vitro and no change in disease outcome was observed in vivo . The data demonstrate that CSP, which induces in vitro a temporary growth arrest through stimulation of its cognate histidine kinase receptor, is able to block systemic disease in mice . This therapeutic effect is novel, in that the drug-like effect is obtained by stimulation, rather than inhibition, of a bacterial drug target.

Antimicrob Agents Chemother, 2004 Dec, 48(12), 4650 - 3
Pharmacokinetics of telithromycin in plasma and soft tissues after single-dose administration to healthy volunteers; Gattringer R et al.; By use of microdialysis we assessed the concentrations of telithromycin in muscle and adipose tissue to test its ability to penetrate soft tissues . The ratios of the area under the concentration-versus-time curve from 0 to 24 h to the MIC indicated that free concentrations of telithromycin in tissue and plasma might be effective against Streptococcus pyogenes but not against staphylococci and human and animal bite pathogens.

Rev Med Liege, 2004 Sep, 59(9), 517 - 21
{Non bullous impetigo: streptococcal or staphylococcal?}; Henno A et al.; Non bullous impetigo is very common among the pediatric population . It is caused by bacteria . For twenty years, Staphylococcus aureus has been the most frequently isolated organism (present in 80 % of non bullous impetigo lesions, it is the only pathogen cultured in 50 % of patients) . The group A beta-haemolytic streptococcus is at the moment isolated alone in 3% of lesions and in association with S.Aureus in 30 % of patients . An epidemiologic change seems to have occurred . Until the early 1980s, group A beta-haemolytic streptococcus was indeed the most predominant etiologic agent causing non bullous impetigo . Unfortunately, the rate of resistance among staphylococci responsible of non bullous impetigo is increasing . As serious complications can follow this skin infection, an appropriate treatment is necessary combining local care, topical antibiotics and sometimes adjunction of systemic antibiotics.

South Med J, 2004 Oct, 97(10), 1018 - 9
Prosthetic valve endocarditis presenting as loss of the metallic click sound; Sreih AG et al.; Prosthetic valve endocarditis is a significant infection . It is often serious, and may result in a complicated course leading to valvular malfunction . We present the case of a 50-year-old male with an aortic Medtronic Hall valve, who presented with loss of his normal metallic click . A transthoracic echocardiogram confirmed the diagnosis of endocarditis and of an aortic-root abscess . Blood cultures were positive for nutritionally deficient Streptococcus . He underwent successful surgery and later was discharged . Patients with mechanical heart valves are often bothered by the metallic sound . It can interfere with their daily life . However, the loss of the click may indicate valvular dysfunction, dehiscence of the prosthesis, and/or tissue infection with abscess formation.

South Med J, 2004 Oct, 97(10), 1004 - 6
Evolving infectious aortitis caused by Streptococcus pneumoniae; Goswami R et al.; Infections of major vessels leading to mycotic aneurysms can be a diagnostic dilemma for clinicians, and can be accompanied by a high mortality rate . Successful treatment of this condition often requires a high index of suspicion and prompt medical and surgical attention . The authors report two cases of infectious aortitis caused by pneumococcus that evolved during hospitalization, and discuss diagnostic difficulties that accompany this entity.

Jpn Heart J, 2004 Sep, 45(5), 885 - 8
A second mitral valve replacement in a patient with hereditary hemorrhagic telangiectasia (Osler's disease); Ishikawa S et al.; A 62-year-old female with Osler's disease was admitted to our hospital because of fever and cardiac failure . The patient had undergone a mitral valve replacement (MVR) using a Carpentier-Edwards prosthetic valve 14 years earlier . A bacterial examination of arterial blood identified Streptococcus mitis . No arteriovenous malformations were detected in visceral organs . The patient underwent MVR using the same prosthetic xenograft after conservative treatment and management of repetitive epistaxis and decayed teeth . Intra- and postoperative bleeding were typical of a mitral valve reoperation . This is the first reported experience, to the best of our knowledge, of a second MVR in a patient with Osler's disease.

Infect Immun, 2004 Dec, 72(12), 7342 - 5
Intranasal vaccination with streptococcal fibronectin binding protein Sfb1 fails to prevent growth and dissemination of Streptococcus pyogenes in a murine skin infection model; McArthur J et al.; Fibronectin binding protein F1 (Sfb1) of Streptococcus pyogenes (group A streptococcus {GAS}) is a well-characterized adhesin that has been shown to induce protection in mice against a lethal intranasal GAS challenge after intranasal immunization with cholera toxin B subunit (CTB) as adjuvant . With a murine skin infection model, we have shown that Sfb1/CTB vaccination neither elicits opsonizing antibodies nor prevents systemic bacterial growth and dissemination to internal organs after a subcutaneous GAS challenge . These results indicate that an Sfb1-based vaccine should be complemented with additional protective antigens in order to be used in areas such as the tropical north of Australia, where the skin is the primary route of entry for invasive streptococcal diseases.

Infect Immun, 2004 Dec, 72(12), 6951 - 60
Redirecting the humoral immune response against Streptococcus mutans antigen P1 with monoclonal antibodies; Oli MW et al.; The adhesin P1 of Streptococcus mutans has been studied as an anticaries vaccine antigen . An anti-P1 monoclonal antibody (MAb) bound to S . mutans prior to mucosal immunization of mice was shown previously to alter the amount, specificity, isotype, and biological activity of anti-P1 antibodies . The present study was undertaken to screen this and four additional anti-P1 MAbs for immunomodulatory activity when complexed with S . mutans and administered by a systemic route and to evaluate sera from immunized mice for the ability to inhibit adherence of S . mutans to immobilized human salivary agglutinin . All five MAbs tested influenced murine anti-P1 serum antibody responses in terms of subclass distribution and/or specificity . The effects varied depending on which MAb was used and its coating concentration . Two MAbs promoted a more effective, and two others a less effective, adherence inhibition response . An inverse relationship was observed between the ability of the MAbs themselves to inhibit adherence and the ability of antibodies elicited following immunization with immune complexes to inhibit adherence . Statistically significant correlations were demonstrated between the levels of anti-P1 serum immunoglobulin G2a (IgG2a) and IgG2b, but not of IgG1 or IgG3, and the ability of sera from immunized animals to inhibit bacterial adherence . These results indicate that multiple anti-P1 MAbs can mediate changes in the immune response and that certain alterations are potentially more biologically relevant than others . Immunomodulation by anti-P1 MAbs represents a useful strategy to improve the beneficial immune response against S . mutans.

J Immunol, 2004 Dec 1, 173(11), 6899 - 904
Interaction between complement regulators and Streptococcus pyogenes: binding of C4b-binding protein and factor H/factor H-like protein 1 to M18 strains involves two different cell surface molecules; Perez-Caballero D et al.; Streptococcus pyogenes, or group A Streptococcus, is one of the most frequent causes of pharyngitis and skin infections in humans . Many virulence mechanisms have been suggested to be involved in the infectious process . Among them is the binding to the bacterial cell surface of the complement regulatory proteins factor H, factor H-like protein 1 (FHL-1), and C4b-binding protein . Previous studies indicate that binding of these three regulators to the streptococcal cell involves the M protein encoded by the emm gene . M-type 18 strains are prevalent among clinical isolates and have been shown to interact with all three complement regulators simultaneously . Using isogenic strains lacking expression of the Emm18 or the Enn18 proteins, we demonstrate in this study that, in contradistinction to previously described S . pyogenes strains, M18 strains bind the complement regulators factor H, FHL-1, and C4b-binding protein through two distinct cell surface proteins . Factor H and FHL-1 bind to the Emm18 protein, while C4BP binds to the Enn18 protein . We propose that expression of two distinct surface structures that bind complement regulatory proteins represents a unique adaptation of M18 strains that enhances their resistance to opsonization by human plasma and increases survival of this particular S . pyogenes strain in the human host . These new findings illustrate that S . pyogenes has evolved diverse mechanisms for recruitment of complement regulatory proteins to the bacterial surface to evade immune clearance in the human host.

Int J Antimicrob Agents, 2004 Dec, 24(6), 616 - 8
Activity of telithromycin against erythromycin-susceptible and -resistant Streptococcus pneumoniae isolates from adults with invasive infections; Ortega M et al.; A telithromycin (TEL) kill-kinetics study was conducted with 120 clinically significant Streptococcus pneumoniae isolates (60 susceptible and 60 highly resistant to erythromycin) . Time-kill curves were performed using different antibiotic concentrations . The minimum inhibitory concentrations (MICs) of TEL were low for both erythromycin-susceptible (MIC < or = 0.016 mg/L) and erythromycin-resistant strains (MIC < or = 0.25 mg/L) . TEL showed 99.9% killing of all erythromycin resistant strains at 18-24 h of incubation . Even for strains with erythromycin MICs > or = 64.0 mg/L, TEL was uniformly bactericidal at 0.25 mg/L.

Int J Antimicrob Agents, 2004 Dec, 24(6), 529 - 35
Role of efflux mechanisms on fluoroquinolone resistance in Streptococcus pneumoniae and Pseudomonas aeruginosa; Zhanel GG et al.; Prokaryotic efflux mechanisms can effectively increase the intrinsic resistance of bacteria by actively transporting antibiotics out of cells, thus reducing the effective concentration of these agents . The fluoroquinolones, similar to most other antimicrobial classes, are susceptible to efflux mechanisms, particularly in Gram-negative organisms, such as Pseudomonas aeruginosa . Resistant P . aeruginosa clones isolated after fluoroquinolone therapy frequently over express at least one of the multiple efflux pump mechanisms found in this organism . Gram-positive bacteria, such as Streptococcus pneumoniae, also possess efflux mechanisms, though their effect on fluoroquinolone resistance seems to be more limited and selective . In the future, efflux pump inhibitors may offer effective adjunctive therapy to antibiotics for the treatment of difficult infections by efflux mutants . In the meantime, appropriate antibiotic selection and optimal dosing strategies should aim to eradicate the causative pathogen before a resistant efflux mutant can emerge.

Infect Dis Clin North Am, 2004 Dec, 18(4), 963 - 74; x-xi
Re-evaluation of the therapy of severe pneumonia caused by Streptococcus pneumoniae; Plouffe JF Jr et al.; Pneumonia caused by Streptococcus pneumoniae is the most deadly form of community-acquired pneumonia . The death rate of bacteremic pneumococcal pneumonia has remained constant over the past 50 years . Several retrospective reviews of bacteremic pneumococcal pneumonia suggest that dual therapy with a beta-lactam and a macrolide antimicrobial agent is associated with a lower case fatality rate than therapy with a beta-lactam alone . These studies are reviewed, potential mechanisms are suggested, and future studies are discussed.

Microbes Infect, 2004 Nov, 6(14), 1241 - 9
Essential role for the p40 subunit of interleukin-12 in neutrophil-mediated early host defense against pulmonary infection with Streptococcus pneumoniae: involvement of interferon-gamma; Yamamoto N et al.; Interleukin (IL)-12 is a critical cytokine in the T helper (Th)1 response and host defense against intracellular microorganisms, while its role in host resistance to extracellular bacteria remains elusive . In the present study, we elucidated the role of IL-12 in the early-phase host defense against acute pulmonary infection with Streptococcus pneumoniae, a typical extracellular bacterium, using IL-12p40 gene-disrupted (IL-12p40KO) mice . IL-12p40KO mice were highly susceptible to S . pneumoniae infection, as indicated by the shortened survival time, which was completely restored by the replacement therapy with recombinant (r) IL-12, and increased bacterial counts in the lung . In these mice, recruitment of neutrophils in the lung was significantly attenuated when compared to that in wild-type (WT) mice, which correlated well with the reduced production of macrophage inflammatory protein (MIP-2) and tumor necrosis factor (TNF)-alpha in the infected tissues at the early phase of infection . In vitro synthesis of both cytokines by S . pneumoniae-stimulated lung leukocytes was significantly lower in IL-12p40KO mice than in WT mice, and addition of rIL-12 or interferon (IFN)-gamma restored the reduced production of MIP-2 and TNF-alpha in IL-12p40KO mice . Neutralizing anti-IFN-gamma monoclonal antibody (mAb) significantly decreased the effect of rIL-12 . Anti-IFN-gamma mAb shortened the survival time of infected mice and reduced the recruitment of neutrophils and production of MIP-2 and TNF-alpha in the lungs . Our results indicated that IL-12p40 plays a critical role in the early-phase host defense against S . pneumoniae infection by promoting the recruitment of neutrophils to the infected tissues.

Mol Microbiol, 2004 Dec, 54(5), 1250 - 68
CovS/CovR of group B streptococcus: a two-component global regulatory system involved in virulence; Lamy MC et al.; In this study, we carried out a detailed structural and functional analysis of a Streptococcus agalactiae (GBS) two-component system which is orthologous to the CovS/CovR (CsrS/CsrR) regulatory system of Streptococcus pyogenes . In GBS, covR and covS are part of a seven gene operon transcribed from two promoters that are not regulated by CovR . A DeltacovSR mutant was found to display dramatic phenotypic changes such as increased haemolytic activity and reduced CAMP activity on blood agar . Adherence of the DeltacovSR mutant to epithelial cells was greatly increased and analysis by transmission electron microscopy revealed the presence at its surface of a fibrous extracellular matrix that might be involved in these intercellular interactions . However, the DeltacovSR mutant was unable to initiate growth in RPMI and its viability in human normal serum was greatly impaired . A major finding of this phenotypic analysis was that the CovS/CovR system is important for GBS virulence, as a 3 log increase of the LD(50) of the mutant strain was observed in the neonate rat sepsis model . The pleiotropic phenotype of the DeltacovSR mutant is in full agreement with the large number of genes controlled by CovS/CovR as seen by expression profiling analysis, many of which encode potentially secreted or cell surface-associated proteins: 76 genes are repressed whereas 63 were positively regulated . CovR was shown to bind directly to the regulatory regions of several of these genes and a consensus CovR recognition sequence was proposed using both DNase I footprinting and computational analyses.

Zh Mikrobiol Epidemiol Immunobiol, 2004 Sep-Oct, (5), 7 - 12
{Etiology of the epidemic outbreak of outhospital pneumonia in children in St . Petersburg}
{Molecular surveillance of invasive penicillin-resistant Streptococcus pneumoniae Colombian isolates recovered from children less than 5 years of age}
Moreno J, Phandanouvong V, Castaneda E.

Grupo de Microbiologia, Instituto Nacional de Salud, Bogota, DC, ColombiaThe rapid increase of penicillin-resistant Streptococcus pneumoniae isolates could be a consequence of the spread of clones or due to the antimicrobial selective pressure . The genetic relatedness of 190 invasive isolates S . pneumoniae with reduced susceptibility to penicillin recovered from Colombian children less than 5 years old during a surveillance study from 2000 to 2003 was determined by the use of pulsed-field electrophoresis (PFGE) . Overall, 42 different PFGE patterns were identified, but 4 of them included 76% of all isolates . They were related with international clones 1-Spain23F, 2-Spain6B, 3-Spain9V and 26-Colombia23F . Our results indicated that the dissemination of penicillin-resistant S . pneumoniae was the result of the spread of international clones, specially, the 3-Spain9V clone.

J Infect Dis, 2004 Dec 15, 190(12), 2154 - 61 Epub 2004 Dec 15.
Emergence of penicillin-nonsusceptible Streptococcus pneumoniae clones expressing serotypes not present in the antipneumococcal conjugate vaccine; Porat N et al.; BACKGROUND: Penicillin-nonsusceptible Streptococcus pneumoniae isolates are confined mainly to a few serogroups . Capsular transformation may serve as a mechanism for spreading antibiotic resistance to new serotypes . METHODS: Antibiogram and molecular typing, by pulsed-field gel electrophoresis (PFGE), were performed on 46 nasopharyngeal and middle ear fluid (MEF) isolates expressing serotype 11A, 45 MEF isolates expressing serotype 15B/C (recovered during 1998-2003 from Israeli children <5 years old), and 57 MEF isolates expressing serotype 19F (recovered during 1998-2001 from Costa Rican children <7.5 years old) . RESULTS: PFGE patterns showed that 49 (86%) of 57 serotype 19F isolates and 19 (41%) of 46 serotype 15B/C isolates were closely related . The vast majority of these isolates (80% of serotype 19F and 100% of serotype 15B/C isolates) were nonsusceptible to penicillin . Multilocus sequence typing (MLST) data show that the serotype 15B/C isolates belonged to the ST346 cluster, whereas the serotype 19F isolates were a single-locus variant of ST346 . For serotype 11A isolates, PFGE patterns and MLST analysis showed that 8 (80%) of the 10 penicillin-nonsusceptible isolates belonged to a single clone--namely, ST156--which was identical to the international Spain9V-3 clone . CONCLUSIONS: Penicillin-nonsusceptible pneumococcal clones of serotypes not related to those included in the 11-valent conjugate vaccines may derive from capsular transformation of vaccine-related serotypes . Of particular concern was the detection of serotype 11A variants of the successful international Spain9V-3 clone . This phenomenon, although seemingly rare at present, can have implications for the long-term effectiveness of the conjugate vaccines.

Int Endod J, 2004 Dec, 37(12), 819 - 27
Investigation of the effect of the coronal restoration quality on the composition of the root canal microflora in teeth with apical periodontitis by means of T-RFLP analysis; Hommez GM et al.; AIM: To investigate the effect of the radiographic and clinical quality of coronal restorations on the composition of the root canal flora of teeth with necrotic pulps and teeth with root fillings associated with apical periodontitis . METHODOLOGY: Twenty-eight necrotic pulps and 35 root filled canals with signs of apical periodontitis were studied . Both the coronal filling (presence of radiographically or clinically deficient margins and/or secondary caries) and the root filling (homogeneity and length) were scored . Bacterial root canal samples were taken with sterile paper points under rubber dam and using measures to prevent contamination . A DNA-based nonculture bacterial identification technique was used, namely terminal restriction fragment length polymorphism (T-RFLP) analysis . RESULTS: Twelve samples were negative for bacterial DNA . A total of 33 different terminal restriction fragments (TRFs) were detected . The Fusobacterium nucleatum/Streptococcus mitis group was the most frequently encountered TRF . The mean number of TRFs per necrotic pulp was 6.2 and 5.8 for the groups with acceptable and unacceptable coronal restorations, respectively . This difference was not significant . In the root filled group, these values (respectively, 5.2 and 8.6) were statistically significantly different (P < 0.05) . The following parameters in root filled teeth had no significant influence on the mean numbers of TRFs detected: the length and homogeneity of the root filling and the type of tooth (anterior-premolar-molar) . CONCLUSION: T-RFLP allowed the rapid assessment of bacterial biodiversity in root canal samples . The technique revealed the presence of bacteria that have rarely been described in the root canals of teeth with apical periodontitis . Biodiversity in the root filled group was high, as compared with culture-dependent studies where monoinfections were more frequently reported . Only in root filled teeth did defective coronal restorations have a statistically significant influence on the mean numbers of detected TRFs per sample.

J Bacteriol, 2004 Dec, 186(23), 8123 - 36
Regulation of iron transport in Streptococcus pneumoniae by RitR, an orphan response regulator; Ulijasz AT et al.; RitR (formerly RR489) is an orphan two-component signal transduction response regulator in Streptococcus pneumoniae that has been shown to be required for lung pathogenicity . In the present study, by using the rough strain R800, inactivation of the orphan response regulator gene ritR by allele replacement reduced pathogenicity in a cyclophosphamide-treated mouse lung model but not in a thigh model, suggesting a role for RitR in regulation of tissue-specific virulence factors . Analysis of changes in genome-wide transcript mRNA levels associated with the inactivation of ritR compared to wild-type cells was performed by the use of high-density DNA microarrays . Genes with a change in transcript abundance associated with inactivation of ritR included piuB, encoding an Fe permease subunit, and piuA, encoding an Fe carrier-binding protein . In addition, a dpr ortholog, encoding an H(2)O(2) resistance protein that has been shown to reduce synthesis of reactive oxygen intermediates, was activated in the wild-type (ritR(+)) strain . Microarray experiments suggested that RitR represses Fe uptake in vitro by negatively regulating the Piu hemin-iron transport system . Footprinting experiments confirmed site-specific DNA-binding activity for RitR and identified three binding sites that partly overlap the +1 site for transcription initiation upstream of piuB . Transcripts belonging to other gene categories found to be differentially expressed in our array studies include those associated with (i) H(2)O(2) resistance, (ii) repair of DNA damage, (iii) sugar transport and capsule biosynthesis, and (iv) two-component signal transduction elements . These observations suggest that RitR is an important response regulator whose primary role is to maintain iron homeostasis in S . pneumoniae . The name ritR (repressor of iron transport) for the orphan response regulator gene, rr489, is proposed.

J Bacteriol, 2004 Dec, 186(23), 7847 - 57
Transcriptional activation of sclA by Mga requires a distal binding site in Streptococcus pyogenes; Almengor AC et al.; Streptococcus pyogenes (the group A streptococcus {GAS}) is a medically significant pathogen of humans, causing a range of diseases from pharyngitis to necrotizing fasciitis . Several important GAS virulence genes are under the control of a pleiotropic regulator called Mga, or the multiple gene regulator of GAS, including the gene encoding the streptococcal collagen-like protein, or sclA . Analysis of the genome sequence upstream of sclA revealed two potential Mga-binding sites with homology to the published Mga-binding element, which were called PsclA-I (distal) and PsclA-II (proximal) based on their location relative to a predicted start of transcription . Primer extension was used to confirm that the Mga-dependent transcriptional start site for sclA was located adjacent to the proximal PsclA-II binding site . By using overlapping PsclA promoter probes and purified Mga-His fusion protein, it was shown by electrophoretic mobility shift assays that, unlike other Mga-regulated promoters, Mga binds only to a distal DNA-binding site (PsclA-I) . Binding of Mga to PsclA-I could be competed with cold probes corresponding to known Mga-regulated promoters (Pemm, PscpA, and Pmga) but not with a nonspecific probe or the proximal PsclA-II fragment . With the use of a plasmid-based green fluorescent protein transcriptional reporter system, the full-length PsclA was not sufficient to reproduce normal Mga-regulated activation . However, studies using a single-copy gusA transcriptional reporter system integrated at the native sclA chromosomal locus clearly demonstrated that the distal PsclA-I binding site is required for Mga regulation . Therefore, PsclA represents a new class of Mga-regulated promoters that requires a single distal binding site for activation.

J Biol Chem . 2004 Nov 16; {Epub ahead of print}
Bass hepcidin: Synthesis, solution structure, antimicrobial activities and synergism, and in vivo hepatic response to bacterial infections; Lauth X et al.; Bass hepcidin was purified from gill of hybrid striped bass (Morone chrysops x M . saxatilis) based on antimicrobial activity against E . coli . This 21 amino acid peptide has 8 cysteines engaged in 4 disulfide bonds and is very similar to human hepcidin, an antimicrobial peptide (AMP) with iron regulatory properties . To gain insight into potential role(s) of bass hepcidin in innate immunity in fish, we synthesized the peptide, characterized its antimicrobial activities in vitro, determined its solution structure by NMR, and quantified hepatic gene expression in vivo following infection of bass with the fish pathogens, Streptococcus iniae or Aeromonas salmonicida . Its structure is very similar to that of human hepcidin, including presence of an anti-parallel ss-sheet, a conserved disulfide-bonding pattern, and a rare vicinal disulfide bond . Synthetic bass hepcidin was active in vitro against Gram-negative pathogens and fungi, but showed no activity against key Gram-positive pathogens and a single yeast strain tested . Hepcidin was non-hemolytic at microbicidal concentrations and had lower specific activity than moronecidin, a broad spectrum, amphipathic, a-helical, AMP constitutively expressed in bass gill tissue . Good synergism between hepcidin's and moronecidin's bacterial killing activities was observed in vitro . Hepcidin gene expression in bass liver increased significantly within hours of infection with Gram-positive (S . iniae) or Gram-negative (A . salmonicida) pathogens and was four to five orders of magnitude above baseline 24-48 h post-infection . Our results suggest that hepcidin plays a key role in the antimicrobial defenses of bass and that its functions are potentially conserved between fish and human.

Clin Infect Dis, 2004 Sep 1, 39 Suppl 3, S159 - 64
Clinical efficacy of newer agents in short-duration therapy for community-acquired pneumonia; File TM Jr; Streptococcus pneumoniae, the most important respiratory tract pathogen implicated in community-acquired pneumonia (CAP), is becoming increasingly resistant in vitro to the beta -lactams and macrolides, and fluoroquinolone resistance has been detected . A growing body of evidence suggests that prolonged antimicrobial use may contribute directly and indirectly to increased antimicrobial resistance among common respiratory pathogens . Long-term exposure to antimicrobial agents, especially less-potent agents, directly increases selection pressure for resistance . Indirectly, poor patient compliance, multiple daily dosing, and the increased risk of adverse events further complicate the resistance issue and diminish the efficacy of long-term antimicrobial use . Controlled clinical trials addressing the appropriate duration of therapy for CAP are lacking . However, available data suggest that with appropriate antibiotic selection, based on appropriate spectrum, potency, and pharmacokinetic/pharmacodynamic profile, lower respiratory tract infections in outpatients can be successfully treated in <7 days rather than the 7-14 days currently recommended.

Clin Infect Dis, 2004 Sep 1, 39 Suppl 3, S142 - 50
Increased antibiotic resistance in respiratory tract pathogens: PROTEKT US--an update; Karchmer AW; Three major North American surveillance programs have tracked antimicrobial resistance patterns among isolates of Streptococcus pneumoniae and other common respiratory tract pathogens . The Canadian Bacterial Surveillance Network shows the progressive increase in resistance among pneumococcal S . pneumoniae to penicillin, trimethoprim-sulfamethoxazole, macrolides, and fluoroquinolones . The data from the Tracking Resistance in the United States Today study also show a steady rise in pneumococcal resistance among common antibiotics as well as an increase in multidrug-resistant S . pneumoniae . The US component of the Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin study has detected increasing resistance to many antimicrobial agents among common respiratory isolates, with marked geographic variations in resistance patterns . The patterns of resistance detected by these major surveillance programs are a warning signal regarding the continued emergence of resistance among community-acquired respiratory tract pathogens.

Pediatr Infect Dis J, 2004 Nov, 23(11), 1015 - 22
Seven valent pneumococcal conjugate vaccine immunization in two Boston communities: changes in serotypes and antimicrobial susceptibility among Streptococcus pneumoniae isolates; Pelton SI et al.; BACKGROUND: Seven valent pneumococcal conjugate vaccine (PCV7) was licensed and introduced in 2000 for universal administration of children younger than 2 years of age and for selective immunization of children 2-5 years of age . SPECIFIC AIMS: To identify changes in colonization and antimicrobial susceptibility among Streptococcus pneumoniae organisms after introduction of PCV7 . METHODS: Infants and children ages 2-24 months were enrolled in surveillance study of nasopharyngeal carriage of S . pneumoniae . Nasopharyngeal cultures for S . pneumoniae were performed at all well child visits and illness visits of children with acute otitis media . S . pneumoniae organisms were serotyped, and antimicrobial susceptibilities to penicillin, amoxicillin, trimethoprim-sulfamethoxazole and azithromycin were performed . RESULTS: During the 3-year period (October 2000 through September 2003), nasopharyngeal colonization with vaccine serotypes declined from 22% to 2%, and nonvaccine serotypes increased from 7% to 16% . Rates of antibiotic resistance of S . pneumoniae isolates to penicillin, amoxicillin, azithromycin and trimethoprim-sulfamethoxazole were 29.3, 2.2, 26.5 and 28.1%, respectively . CONCLUSIONS: PCV7 immunization produces a marked decline in vaccine serotypes carried in the nasopharynx of young children, with a coincident rise in the prevalence of nonvaccine serotypes . Important shifts in antimicrobial susceptibility have not been observed to date.

Int J Syst Evol Microbiol, 2004 Nov, 54(Pt 6), 2291 - 6
Streptococcus equi subsp . ruminatorum subsp . nov., isolated from mastitis in small ruminants; Fernandez E et al.; Six isolates of an unknown Gram-positive, catalase-negative, chain-forming, coccus-shaped organism isolated from ovine and caprine mastitis were characterized by phenotypic and molecular taxonomic methods . On the basis of cellular morphology and the results of biochemical tests, the organism was tentatively identified as a streptococcal species . Comparative 16S rRNA gene sequencing studies confirmed that the organism is a member of the genus Streptococcus, with Streptococcus equi as its closest phylogenetic relative (98.8 % similarity) . DNA-DNA pairing studies showed that the unidentified organism displayed more than 70 % relatedness to the type strains of S . equi subsp . equi and subsp . zooepidemicus . Despite the relatively high DNA-DNA reassociation values, biotyping and ribotyping allowed clear differentiation of the unknown bacterium from the two recognized subspecies of S . equi . On the basis of phenotypic and molecular genetic evidence, it is proposed that the unknown Streptococcus isolates from ovine and caprine mastitis be classified as a novel subspecies, Streptococcus equi subsp . ruminatorum subsp . nov . The type strain is CECT 5772(T) (=CCUG 47520(T)=Mt 167(T)).

J Clin Pharmacol, 2004 Dec, 44(12), 1391 - 7
A randomized crossover study investigating the influence of ranitidine or omeprazole on the pharmacokinetics of cephalexin monohydrate; Madaras-Kelly K et al.; Limited data characterize pharmacokinetic interactions between cephalexin and ranitidine, and no data exist for an interaction with proton pump inhibitors . The purpose of this study was to investigate the effects of ranitidine or omeprazole administration on the pharmacokinetics and pharmacodynamics of cephalexin . A randomized single- and multiple-dose crossover study was conducted in healthy subjects ingesting cephalexin before and after steady-state administration of ranitidine or omeprazole . Time-concentration profiles were determined and pharmacokinetic parameters were characterized using noncompartmental methods . Pharmacokinetic data were analyzed in accordance with the two 1-sided test for bioequivalence . The percentage of time that serum concentrations remain above the MIC(90) during the dosing interval (T > MIC(90)) for Streptococcus pyogenes and Staphylococcus aureus associated with the pharmacokinetic profiles was calculated . The coadministration of cephalexin with ranitidine or omeprazole resulted in relatively minor changes in C(max), AUC(infinity), t(1/2), or CL/F . t(max) was significantly prolonged when cephalexin was administered with ranitidine or omeprazole . Suboptimal T > MIC(90) was observed for cephalexin irrespective of acid suppression . Delay in absorption of cephalexin resulted in a decrease in the percentage of T > MIC(90) for certain acid-suppressive regimens and pathogen combinations . With the exception of an increase in t(max), there were no significant pharmacokinetic interactions between cephalexin and ranitidine or omeprazole . Delayed t(max) associated with acid suppression may result in a diminished T > MIC(90).

Biochemistry, 2004 Nov 23, 43(46), 14594 - 601
Molecular functions of conserved aspects of the GHMP kinase family; Andreassi JL 2nd et al.; The sequences and three-dimensional structures of the galactokinase, homoserine kinase, mevalonate kinase, and phosphomevalonate kinase (GHMP) family were compared to identify highly conserved surface residues . The functions of these solvent-accessible residues were assessed by determining the effects of their substitution, via mutagenesis, on the initial-rate parameters of a representative member of the GHMP kinase family, phosphomevalonate kinase from Streptococcus pneumoniae . What emerges from this study is a profile of the conserved surface-linked functions of the family . Certain substitutions produce highly selective effects on the steady-state affinity of a particular substrate, while one residue, Asp150, appears to be a pure k(cat) effector . Substitutions elsewhere affect multiple initial-rate parameters with varying, and sometimes compensatory, patterns . An alpha-helix that repositions during catalysis was substituted along its length to assess how its different segments contribute to catalysis-the substrate-proximal edge of the helix affects ATP recognition and k(cat), while the distal edge affects recognition of both substrates without affecting turnover . GHMP kinase mutations at the conserved surface residues corresponding to Ser291 and Ala293 in phosphomevalonate kinase are linked to mevalonic acid deficiency, which can lead to early fatality, and galactokinase deficiency, which causes cataracts . Our results suggest that the molecular basis for this particular galactokinase deficiency is an increase in the K(m) for galactose.

Rev Neurol, 2004 Nov 1-15, 39(9), 810 - 5
{Sydenham's chorea . A clinical analysis of 55 patients with a prolonged follow-up}; Diaz-Grez F et al.; INTRODUCTION: Sydenham's chorea is permanently on the rise in developing countries and may suddenly reappear in developed nations . PATIENTS AND METHODS: We studied a prospective series of 55 cases, involving a total of 89 outbreaks with long-term follow-ups . All the cases were considered to be rheumatic from the outset, whether they were pure choreas or accompanied by the other signs from the Jones criterion, 38 and 17 respectively, in the first outbreak . Ages ranged between 7 and 22 years, with a mean of 15, at the time of the first outbreak; there was a predominance of females (87%) . RESULTS: Hemichorea accounted for 54% of cases . Presentation under treatment was mild (60%), moderate (27%) and severe (13%) . Duration ranged from 30 to 365 days . Most of the patients presented just one outbreak and only 18% had multiple outbreaks, between 2 and 10 in number . Ballism was observed in five patients, a state of chorea in two of them, another two had chorea mollis and corea gravidarum was found in five of the patients . Chorea was associated to hypotonia, incoordination, fatigue, postural disorders, motor impersistence, dysarthria and altered gait . Psychiatric disorders were frequent and varied, the most predominant being anguish, irritability, psychomotor restlessness, obsessive-compulsive traits and insomnia . The only important sequela involved the heart, with 10 cases, two of which required surgery . CONCLUSIONS: Crystalline penicillin was used to eradicate streptococcus, neuroleptic agents were employed to reduce involuntary movements and psychiatric symptoms, and benzathine was utilised as a prophylaxis for relapses and sequelae.

Nat Struct Mol Biol, 2004 Dec, 11(12), 1173 - 8 Epub 2004 Dec.
Human CD59 is a receptor for the cholesterol-dependent cytolysin intermedilysin; Giddings KS et al.; Cholesterol is believed to serve as the common receptor for the cholesterol-dependent cytolysins (CDCs) . One member of this toxin family, Streptococcus intermedius intermedilysin (ILY), exhibits a narrow spectrum of cellular specificity that is seemingly inconsistent with this premise . We show here that ILY, via its domain 4 structure, binds to the glycosyl-phosphatidylinositol-linked membrane protein human CD59 (huCD59) . CD59 is an inhibitor of the membrane attack complex of human complement . ILY specifically binds to huCD59 via residues that are the binding site for the C8alpha and C9 complement proteins . These studies provide a new model for the mechanism of cellular recognition by a CDC.

Vaccine, 2004 Dec 21, 23(6), 789 - 93
Characterization of antibodies to PspA and PsaA in adults over 50 years of age with invasive pneumococcal disease; Baril L et al.; We characterized antibody responses to two Streptococcus pneumoniae surface proteins, PspA and PsaA, in 14 adults over 50 years of age hospitalized with invasive pneumococcal disease (IPD), and in two groups of age-matched controls (18 patients with invasive disease due to other microorganisms and 35 patients hospitalized for non infectious conditions) . All patients with IPD and all control subjects had detectable antibodies to both proteins on hospital admission . Three weeks later, the geometric mean concentrations of antibodies to PspA and PsaA in IPD patients were respectively 10 and 25 times higher than on admission . In contrast, acute and convalescent antibody levels were similar in control patients with invasive diseases due to other microorganisms.

Eur J Cardiothorac Surg, 2004 Dec, 26(6), 1104 - 11
Surgical results for active endocarditis with prosthetic valve replacement: impact of culture-negative endocarditis on early and late outcomes; Murashita T et al.; OBJECTIVE: Surgical treatment of active infective endocarditis requires not only hemodynamic repair, but also special emphasis on the eradication of the infectious focus to prevent recurrence . This goal can be achieved by the combination of aggressive debridement of infective tissue and appropriate and adequate antibiotic treatment . We reviewed our experience with active endocarditis and identified factors determining early and late outcomes, particularly focusing on the factor of culture-negative endocarditis . METHODS: Sixty seven patients with clinical evidence of active endocarditis who underwent operation between 1991 and 2001 were evaluated . The aortic valve was infected in 28 (42%), the mitral valve in 23 (34%), and multiple valves in 16 (24%) . Native valve endocarditis was present in 58 (87%) and prosthetic valve endocarditis in 9 (13%) . Mean follow-up was 5.7 years (range, 0.2-11.5 years) . RESULTS: Microorganisms were detected in 46 (69%): Staphylococcus aureus in 9 (13%), other staphylococci in 9 (13%), streptococcus species in 19 (28%), and others in 9 (28%), whereas 21 (31%) patients had culture-negative endocarditis . Operative mortality was 17.8% (12 patients) . Reoperation was required in 8 (12%), while 3 late deaths (5.5% of hospital survivors) occurred . All events, including death, reoperation, periprosthetic leak, and recurrence of infection, occurred within 2 years after operation . Actuarial freedom from reoperation, late survival, and events at 5 years were 81.6, 76.4, and 68.6%, respectively . On multivariate analysis, no independent adverse predictor was detected for hospital death, whereas the following independent adverse predictors were identified: preoperative heart failure (P=0.0375), prosthetic valve endocarditis (P=0.0391) and culture-negative endocarditis (P=0.0354) for poor late survival; culture-negative endocarditis (P=0.0354) and annular abscess (P=0066) for poor event-free survival . Freedom from events was similar between patients with Staphylococcus aureus infection (3-year freedom 55.6%) and culture-negative endocarditis (3-year freedom 47.6%), whereas events were significantly low in patients with streptococcus infection (3-year freedom 100%) . CONCLUSIONS: In our analysis, no independent adverse predictor was detected for hospital death; however, culture-negative endocarditis was identified as an independent predictor for both late survival and events after surgery . Event-free survivals were similar between staphylococcus infection and culture-negative endocarditis, and all events occurred within 2 years after operation, suggesting the necessity of close follow-up during that period.

Diagn Microbiol Infect Dis, 2004 Nov, 50(3), 213 - 7
Bactericidal activity of garenoxacin tested by kill-curve methodology against wild type and QRDR mutant strains of Streptococcus pneumoniae; Anderegg TR et al.; Kill-curve bactericidal assays over 24 hours were determined for garenoxacin, a novel des-F(6) quinolone, and levofloxacin at achievable serum drug concentrations ranging from 2 to 8 microg/mL . Tested strains included 4 wild type and 2 target quinolone resistance-determining region (QRDR) mutant Streptococcus pneumoniae . Garenoxacin was 16-fold to 32-fold more active than levofloxacin, and mutant strains (3 QRDR sites) had garenoxacin minimum inhibitory concentration (MIC) values at 1 microg/mL (levofloxacin MIC >32 microg/mL, resistant), but equal to the levofloxacin potency against wild type strains . Garenoxacin killed mutant pneumococci with comparable rapidity, as did levofloxacin versus strains without target alterations . Garenoxacin appears to be a widely usable and highly active agent against S . pneumoniae resistant to other quinolones such as levofloxacin.

Clin Diagn Lab Immunol, 2004 Nov, 11(6), 1064 - 9
Assignment of weight-based antibody units for 13 serotypes to a human antipneumococcal standard reference serum, lot 89-S(f); Quataert SA et al.; Weight-based immunoglobulin G (IgG), IgM, IgA, and total Ig antibody assignments were made to human antipneumococcal standard reference serum lot 89-S, also known as lot 89-SF, for Streptococcus pneumoniae capsular polysaccharide (PnPs) serotypes 2, 6A, 8, 9N, 10A, 11A, 12F, 15B, 19A, 17F, 20, 22F, and 33F, as well as for C-polysaccharide (C-Ps), extending the standard's usefulness for pneumococcal vaccine evaluation beyond the original serotype 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F assignments (S . A . Quataert, C . S . Kirch, L . J . Quackenbush Wiedl, D . C . Phipps, S . Strohmeyer, C . O . Cimino, J . Skuse, and D . V . Madore, Clin . Diagn . Lab . Immunol . 2:590-597, 1995) . The additional 14 assignments were determined using an equivalence of absorbance method with an anti-PnPs serotype 6B reference enzyme-linked immunosorbent assay (EIA) . To assure accuracy, anti-PnPs EIA for serotype 14 antibodies, a previously assigned serotype, was performed concurrently . This method assures consistency of the new microgram-per-microliter assignments with previous antiserotype assignments to lot 89-S . The sum of the experimentally derived isotype assignments for anti-PnPs serotypes in lot 89-S agrees well with the separately determined total Ig assignment for each serotype . The lot 89-S assignments for serotypes 1, 5, 6B, 14, 18C, 19F, and 23F were used for pneumococcal conjugate vaccine clinical trial evaluation and to generate data in efficacy trials where serological correlates for protection have been proposed . The assignment of antibody concentrations to additional pneumococcal serotypes in this reference reagent facilitates the consistent and accurate comparison of serum antibody concentrations across clinical trials.

Clin Diagn Lab Immunol, 2004 Nov, 11(6), 1035 - 9
Antigenic determinants of alpha-like proteins of Streptococcus agalactiae; Maeland JA et al.; The majority of group B streptococcus (GBS) isolates express one or more of a family of surface-anchored proteins that vary by strain and that form ladder-like patterns on Western blotting due to large repeat units . These proteins, which are important as GBS serotype markers and as inducers of protective antibodies, include the alpha C (Calpha) and R4 proteins and the recently described alpha-like protein 2 (Alp2), encoded by alp2, and Alp3, encoded by alp3 . In this study, we examined antigenic determinants possessed by Alp2 and Alp3 by testing of antibodies raised in rabbits, mainly by using enzyme-linked immunosorbent assays (ELISA) and an ELISA absorption test . The results showed that Alp2 and Alp3 shared an antigenic determinant, which may be a unique immunological marker of the Alp variants of GBS proteins . Alp2, in addition, possessed an antigenic determinant which showed specificity for Alp2 and a third determinant which showed serological cross-reactivity with Calpha . Alp3, in addition to the determinant common to Alp2 and Alp3, harbored an antigenic site which also was present in the R4 protein, whereas no Alp3-specific antigenic site was detected . These ELISA-based results were confirmed by Western blotting and a fluorescent-antibody test . The results are consistent with highly complex antigenic structures of the alpha-like proteins in a fashion which is in agreement with the recently described structural mosaicism of the alp2 and alp3 genes . The results are expected to influence GBS serotyping, immunoprotection studies, and GBS vaccine developments.

J Nutr Biochem, 1990 Feb, 1(2), 89 - 97
Formation of trimethylamine from dietary choline by streptococcus sanguis I, which colonizes the mouth; Chao CK et al.; Choline is a component of the normal diet, and when humans ingest large amounts they excrete trimethylamine (which can impart a fishy body odor) . In the presence of nitrite, trimethylamine can be converted to dimethylnitrosamine, a potent carcinogen . Bacteria in the large intestine metabolize choline to form trimethylamine . We determined that a bacterium normally present in the oral cavity also has this capacity . Mixed bacterial flora cultured from dental plaque and saliva converted choline to trimethylamine . The only organism with trimethylamine-forming capability isolated from these mixed cultures was identified as Streptococcus sanguis I (a facultative anaerobe) . The other products formed when choline was cleaved were ethanol and acetate . The formation of trimethylamine by S . sanguis I was enzyme-mediated . Activity was destroyed by heating at 100 degrees C, and obeyed Michaelis-Menten kinetics ( {Formula: see text} for choline = 184 +/- 58 muM; {Formula: see text} = 1.7 +/- 0.1 mumol/mg protein/h) . Activity was maximal at pH 7.5 to 8.5, was membrane-bound, and required a divalent metal cation (cobalt or iron) . More trimethylamine was produced by bacteria incubated under a nitrogen than under an aerobic atmosphere . Activity was inhibited by deanol, betaine aldehyde, hemicholinium-3, iodoacetate, semicarbazide, and 2,4-dinitrophenol, and was enhanced by sulfhydryl-reducing agents (glutathione, 2-mercaptoethanol, DL-dithiothreitol) and sodium bisulfite . The enzyme activity that we describe in S . sanguis I is similar to that previously described in the anaerobic bacteria isolated from intestinal flora.

FEMS Microbiol Rev, 2004 Nov, 28(5), 553 - 80
Recent trends on the molecular biology of pneumococcal capsules, lytic enzymes, and bacteriophage; Lopez R et al.; Streptococcus pneumoniae has re-emerged as a major cause of morbidity and mortality throughout the world and its continuous increase in antimicrobial resistance is rapidly becoming a leading cause of concern for public health . This review is focussed on the analysis of recent insights on the study of capsular polysaccharide biosynthesis, and cell wall (murein) hydrolases, two fundamental pneumococcal virulence factors . Besides, we have also re-evaluated the molecular biology of the pneumococcal phage, their possible role in pathogenicity and in the shaping of natural populations of S . pneumoniae . Precise knowledge of the topics reviewed here should facilitate the rationale to move towards the design of alternative ways to combat pneumococcal disease.

J Antimicrob Chemother, 2004 Dec, 54(6), 1040 - 4 Epub 2004 Nov 10.
A new phenotype of resistance to lincosamide and streptogramin A-type antibiotics in Streptococcus agalactiae in New Zealand; Malbruny B et al.; OBJECTIVES: To characterize a new type of resistance to clindamycin in Streptococcus agalactiae . METHODS: Nineteen erythromycin-susceptible, clindamycin-resistant S . agalactiae isolates from New Zealand were studied . MICs of macrolide, lincosamide and streptogramin antibiotics were determined . Clindamycin and streptogramin resistance genes were searched for by PCR . Isolates were compared by serotyping and by DNA macrorestriction patterns determined by PFGE . Conjugative transfer of resistance traits to recipient strains of S . agalactiae and Enterococcus faecium was assayed . RESULTS: The 19 S . agalactiae isolates were intermediate or resistant to clindamycin (MIC range: 0.5-2 mg/L) and lincomycin (MIC range: 1-8 mg/L) and had high MICs of dalfopristin (4-32 mg/L), a streptogramin A-type antibiotic, compared with controls . By contrast, the strains were susceptible to macrolides and quinupristin, a streptogramin B-type antibiotic . This new phenotype was called LSA (lincosamide-streptogramin A) . Clindamycin resistance could not be transferred to recipient strains . Thirteen isolates belonged to serotype III and to a single PFGE genotype A, and five isolates belonged to serotype I and to genotype B . One isolate was non-typeable and belonged to a distinct genotype C . CONCLUSIONS: We have characterized a new LSA phenotype in S . agalactiae . Analysis of restriction patterns of S . agalactiae chromosomal DNA showed that the resistance was spread in a minimum of three bacterial clones . The genetic and biochemical basis for the resistance remains unknown.

Med Clin (Barc), 2004 Oct 30, 123(15), 575 - 7
{Risk factors of mortality in invasive pneumococcal disease}; Barahona Rondon L et al.; BACKGROUND AND OBJECTIVE: To analyze the risk factors associated with mortality in invasive pneumococcal disease in the university hospital Fundacion Jimenez Diaz (Madrid, Spain) during 11 years . PATIENTS AND METHOD: We performed a retrospective study of patients attending the emergency service of the hospital from January 1993 to August 2003 . We registered data on mortality, clinical and microbiological evolution and relapses . RESULTS: We studied 263 patients with pneumococcal baceteremia and invasive disease caused by Streptococcus pneumoniae (pneumonia, meningitis, sepsis, bacteremia of unknown origin and oligoarthritis) . Mortality was 12.5% . Variables associated with mortality in a logistic regression analysis included absence of leukocytosis (p = 0.04), acidosis (p < 0.01), respiratory signs and symptoms (tachypnea, pleuritic pain) (p = 0.02), and neurologic manifestations (decreased consciousness level; (p < 0.01) . CONCLUSION: Patients at highest risk of death because of invasive pneumococcal disease are critically ill, with no leukocytosis, with severe respiratory or neurological symptoms and undergoing invasive procedures such as mechanical ventilation and tracheostomy.

Ann Otol Rhinol Laryngol, 2004 Oct, 113(10), 846 - 52
Factors associated with clinical outcomes in acute otitis media; Hotomi M et al.; Acute otitis media (AOM) is a common disease in childhood . If predictors of outcome in AOM were known, it would be possible to individualize therapy . Our aim was to identify factors that predict the outcome in AOM . We enrolled 368 children with AOM (ages, 10 to 86 months) . The severity of symptoms and the severity of tympanic membrane changes were graded with a scoring system . Nasopharyngeal colonization with middle ear pathogens was determined on day 1 . Three outcomes were assessed: persistence of symptoms at day 5, persistence of tympanic membrane changes at day 28, and recurrence of acute symptoms prior to day 28 . Persistence of symptoms at day 5 was associated with younger age (35 versus 44 months; p < .001), higher symptom score on day 1 (3.5 versus 2.9; p < .05), and colonization with Streptococcus pneumoniae (61% versus 41%; p < .05) . Persistence of tympanic membrane changes at day 28 was associated with younger age (39 versus 45 months; p < .01), higher tympanic membrane score on day 1 (4.1 versus 3.6; p < .01), and nasopharyngeal colonization with S . pneumoniae, especially drug-resistant S . pneumoniae (33% versus 13%; p < .05) . Recurrence of acute symptoms prior to day 28 occurred in 14% of the children . Streptococcus pneumoniae was the only pathogen associated with an increased recurrence rate (23%) as compared to the group without pathogens (7%; p < .05) . Age, severity of disease at presentation, and nasopharyngeal colonization patterns were proven to be important determinants of outcome in AOM.

Spine, 2004 Sep 1, 29(17), E373 - 5
Thoracic spondylitis from a mycotic (Streptococcus pneumoniae) aortic aneurysm: a case report; Englert C et al.; STUDY DESIGN: We report on a 54-year-old man with chronic lower back pain after recent streptococcus pneumoniae pulmonary infection, resulting in a mycotic aortic aneurysm and spondylodiscitis of the eighth vertebrae 6 months later . Successful surgical treatment and recurrence-free survival after 4 years are described . SUMMARY OF BACKGROUND DATA: Osteomyelitis by Streptococcus pneumoniae of the spine combined with contained rupture of a mycotic aortic aneurysm into lung and spine has not been reported to date . Mycotic aneurysms with pulmonary fistulas are reported to carry a mortality rate of up to 100% . Few cases have been reported with different operative and conservative strategies . METHODS: The mycotic aortic aneurysm was excised using extracorporeal circulation and replaced by a Dacron graft . The spondylitic section of the eighth thoracic vertebrae was radically resected, and a tricortical bone block from the iliac crest was inserted into the defect . To keep compartments separated, collagen sponges with antibiotic supplementation were used . A triple antibiotic therapy (Metronidazol 3 x 0.5 g/day, Cefotaxim 3 x 2 g/day, and Flucloxacillin 3 x 2 g/day) was prescribed for 6 weeks and changed to Clindamycin for 1 year thereafter . RESULTS: The patient made a good recovery and is free of recurrence 4 years after surgery . CONCLUSIONS: Lower back pain might be a projected pain . Particularly in older patients or in the presence of comorbidities resulting in an immunocompromised status, an aggressive workup may be indicated . Radical resection of inflammatory tissues, sparse use of implant material, and prolonged administration of antibiotics proved a successful strategy in this patient.

Biochemistry, 2004 Nov 16, 43(45), 14403 - 11
Structural studies of metal ions in family II pyrophosphatases: the requirement for a Janus ion; Fabrichniy IP et al.; Family II inorganic pyrophosphatases (PPases) constitute a new evolutionary group of PPases, with a different fold and mechanism than the common family I enzyme; they are related to the "DHH" family of phosphoesterases . Biochemical studies have shown that Mn(2+) and Co(2+) preferentially activate family II PPases; Mg(2+) partially activates; and Zn(2+) can either activate or inhibit (Zyryanov et al., Biochemistry, 43, 14395-14402, accompanying paper in this issue) . The three solved family II PPase structures did not explain the differences between the PPase families nor the metal ion differences described above . We therefore solved three new family II PPase structures: Bacillus subtilis PPase (Bs-PPase) dimer core bound to Mn(2+) at 1.3 A resolution, and, at 2.05 A resolution, metal-free Bs-PPase and Streptococcus gordonii (Sg-PPase) containing sulfate and Zn(2+) . Comparison of the new and old structures of various family II PPases demonstrates why the family II enzyme prefers Mn(2+) or Co(2+), as an activator rather than Mg(2+) . Both M1 and M2 undergo significant changes upon substrate binding, changing from five-coordinate to octahedral geometry . Mn(2+) and Co(2+), which readily adopt different coordination states and geometries, are thus favored . Combining our structures with biochemical data, we identified M2 as the high-affinity metal site . Zn(2+) activates in the M1 site, where octahedral geometry is not essential for catalysis, but inhibits in the M2 site, because it is unable to assume octahedral geometry but remains trigonal bipyramidal . Finally, we propose that Lys205-Gln81-Gln80 form a hydrophilic channel to speed product release from the active site.

Biochemistry, 2004 Nov 16, 43(45), 14395 - 402
Site-specific effects of zinc on the activity of family II pyrophosphatase; Zyryanov AB et al.; Family II pyrophosphatases (PPases), recently found in bacteria and archaebacteria, are Mn(2+)-containing metalloenzymes with two metal-binding subsites (M1 and M2) in the active site . These PPases can use a number of other divalent metal ions as the cofactor but are inactive with Zn(2+), which is known to be a good cofactor for family I PPases . We report here that the Mg(2+)-bound form of the family II PPase from Streptococcus gordonii is nearly instantly activated by incubation with equimolar Zn(2+), but the activity thereafter decays on a time scale of minutes . The activation of the Mn(2+)-form by Zn(2+) was slower but persisted for hours, whereas activation was not observed with the Ca(2+)- and apo-forms . The bound Zn(2+) could be removed from PPase by prolonged EDTA treatment, with a complete recovery of activity . On the basis of the effect of Zn(2+) on PPase dimerization, the Zn(2+) binding constant appeared to be as low as 10(-12) M for S . gordonii PPase . Similar effects of Zn(2+) and EDTA were observed with the Mg(2+)- and apo-forms of Streptococcus mutans and Bacillus subtilis PPases . The effects of Zn(2+) on the apo- and Mg(2+)-forms of HQ97 and DE15 B . subtilis PPase variants (modified M2 subsite) but not of HQ9 variant (modified M1 subsite) were similar to that for the Mn(2+)-form of wild-type PPase . These findings can be explained by assuming that (a) the PPase tightly binds Mg(2+) and Mn(2+) at the M2 subsite; (b) the activation of the corresponding holoenzymes by Zn(2+) results from its binding to the M1 subsite; and (c) the subsequent inactivation of Mg(2+)-PPase results from Zn(2+) migration to the M2 subsite . The inability of Zn(2+) to activate apo-PPase suggests that Zn(2+) binds more tightly to M2 than to M1, allowing direct binding to M2 . Zn(2+) is thus an efficient cofactor at subsite M1 but not at subsite M2.

Int J Med Microbiol, 2004 Oct, 294(5), 277 - 94
Pneumococcal conjugate vaccines--a European perspective; Reinert RR; Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis, and acute otitis media in children and adults worldwide . In the age group of < 2 years the incidence of invasive pneumococcal disease ranges from approximately 14 cases per 100,000 in Germany and the Netherlands and more than 90 per 100,000 children in Spain . The vulnerability of children to S . pneumoniae can also be demonstrated by the high rate of sequelae (> 20% in Germany) and the high mortality (7.5%) in pneumococcal meningitis . Furthermore, antibiotic resistance of S . pneumoniae is increasing in Europe, particularly in France, Spain, and Eastern European countries, whereas Germany and Northern Europe are only marginally affected . A 7-valent pneumococcal conjugate vaccine (7vPCV) that was shown to be highly efficacious in preventing invasive pneumococcal disease in infants in the USA was licensed in Europe in 2001 . It is expected that broad usage of the vaccine would reduce the incidence of invasive pneumococcal disease and the levels of pneumococcal resistance significantly . Important questions have been raised regarding the effectiveness of this vaccine in high-risk populations, serotype replacement, the efficacy of this vaccine in otitis media, and the co-administration of the new vaccine with other standard childhood vaccines used in various European countries . France and Spain currently have the most-wide ranging guidelines recommending pneumococcal vaccination for children . Overall, the development of pneumococcal conjugate vaccines is a significant step in the control of pneumococcal disease in children in Europe . Further progress in pneumococcal vaccine development can be expected from conjugate vaccines including more than seven serotypes (9-valent, 11-valent).

Pediatr Res, 2005 Jan, 57(1), 10 - 5 Epub 2004 Nov 05.
Expression and secretion of cathelicidin antimicrobial peptides in murine mammary glands and human milk; Murakami M et al.; Mammalian milk possesses inherent antimicrobial properties that have been attributed to several diverse molecules . Recently, antimicrobial peptides that belong to the cathelicidin gene family have been found to be important to the mammalian immune response . This antimicrobial is expressed in several tissues and increased in neonatal skin, possibly to compensate for an immature adaptive immune response . We hypothesized that the mammary gland could produce and secrete cathelicidin onto the epithelial surface and into milk . Human cathelicidin hCAP18/LL-37 mRNA was detected in human milk cells by PCR . Quantitative real-time PCR demonstrated an increase in relative expression levels at 30 and 60 d after parturition . Immunohistochemistry of mouse breast tissue identified the murine cathelicidin-related antimicrobial peptide in lobuloacinar and ductules . Western blot analysis of human milk showed that LL-37 was secreted and present in the mature peptide form . The antimicrobial activity of LL-37 against Staphylococcus aureus, group A Streptococcus, and enteroinvasive Escherichia coli O29 in the human milk ionic environment was confirmed by solution colony-forming assay using synthetic peptide . These results indicate that cathelicidin is secreted in mammary gland and human milk, has antimicrobial activity against both Gram-positive and Gram-negative bacteria, and can contribute to the anti-infectious properties of milk.

J Antimicrob Chemother, 2004 Dec, 54(6), 1045 - 50 Epub 2004 Nov 05.
Trends of penicillin and erythromycin resistance among invasive Streptococcus pneumoniae in Europe; Bruinsma N et al.; OBJECTIVES: To forecast trends in resistance to penicillin and erythromycin among Streptococcus pneumoniae in Europe . METHODS: Since 1999, the European Antimicrobial Resistance Surveillance System (EARSS) has collected routine antimicrobial susceptibility test results of S . pneumoniae . To observe and predict changes of reduced susceptibility over time, we used a multinomial logistic regression model . RESULTS: Large variations in penicillin and erythromycin non-susceptibility were observed between countries, and reduced susceptibility to erythromycin (17%) has become more frequent than reduced susceptibility to penicillin (10%) in Europe overall . An overall decrease in single penicillin non-susceptibility, but an increase in dual non-susceptibility was observed, indicating a shift of single penicillin to combined non-susceptibility with erythromycin . By 2006, the proportion of single erythromycin and dual non-susceptibility could increase to as much as 20.4% and 8.9%, respectively . CONCLUSIONS: Our results indicate that appropriately dosed beta-lactams for empirical therapy are still the treatment of choice, and that macrolides should be used with prudence.

J Antimicrob Chemother, 2004 Dec, 54(6), 1035 - 9 Epub 2004 Nov 05.
Emergence of invasive erythromycin-resistant Streptococcus pneumoniae strains in Portugal: contribution and phylogenetic relatedness of serotype 14; Dias R et al.; OBJECTIVES: To study the phenotype and phylogenetic relatedness of invasive Streptococcus pneumoniae strains isolated in Portugal . METHODS: A total of 614 invasive S . pneumoniae strains, isolated in Portugal from 1999 to the first 6 months of 2002, were characterized using serotyping and antimicrobial susceptibility testing . National outpatient sale data for macrolides were compared with erythromycin resistance . We investigated the main clonal lineages from erythromycin-resistant strains of serotype 14 by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) . RESULTS: The emergence of erythromycin-resistant strains correlated well with the usage of azithromycin in Portugal during the period of the study (r=0.900, P=0.001) . Serotype 14 made the largest contribution to this emergence . We found two clonal complexes (CC) among erythromycin-resistant strains: CC1 was formed by three sequence types (ST), ST156, ST143 and ST1042, and CC2 by ST15 and ST9 . All STs described, except ST1042, are putative founders of clonal groups or subgroups from serotype 14 as defined in the pneumococcal MLST database . CONCLUSIONS: This study suggests that macrolides usage is an important factor enhancing the spread of invasive erythromycin-resistant S . pneumoniae clones in Portugal . The study also makes a contribution to the understanding of spread of erythromycin-resistant clones in an international context.

Biomacromolecules, 2004 Nov-Dec, 5(6), 2122 - 7
Evaluation of hyaluronan from different sources: Streptococcus zooepidemicus, rooster comb, bovine vitreous, and human umbilical cord; Shiedlin A et al.; Sodium hyaluronate (HA) is widely distributed in extracellular matrixes and can play a role in orchestrating cell function . Consequently, many investigators have looked at the effect of exogenous HA on cell behavior in vitro . HA can be isolated from several sources (e.g., bacterial, rooster comb, umbilical cord) and therefore can possess diverse impurities . This current study compares the measured impurities and the differences in biological activity between HA preparations from these sources . It was demonstrated that nucleic acid and protein content was highest in human umbilical cord and bovine vitreous HA and was low in bacterial and rooster comb HA . Macrophages exposed to human umbilical cord HA produced significantly higher amounts of TNF-alpha relative to control or bacterial-derived HA . These results indicate that the source of HA should be considered due to differences in the amounts and types of contaminants that could lead to widely different behaviors in vitro and in vivo.

Folia Microbiol (Praha), 2004, 49(4), 387 - 97
Molecular epidemiology of group B streptococcal infections; Tkacikova E et al.; Streptococcus agalactiae (GBS) is a causative agent of sepsis and meningitis in newborns and diseases in pregnant women and nonpregnant adults . Various approaches, including both nongenetic and genetic techniques, are currently used for the study of epidemiology of GBS infections . In the present paper the different methods of molecular epidemiology of GBS infections are reviewed, and several novel approaches are introduced . The advantages and disadvantages of molecular methods are discussed and compared with traditional serotyping technique . The possible use of the molecular approaches for identification of different genetic lineages in GBS as well as for identification and control of the epidemiologically actual clones is discussed.

J Infect Dis, 2004 Dec 1, 190(11), 2031 - 8 Epub 2004 Oct 27.
Impact of a conjugate vaccine on community-wide carriage of nonsusceptible Streptococcus pneumoniae in Alaska; Moore MR et al.; BACKGROUND: Streptococcus pneumoniae is a leading cause of invasive bacterial disease and pneumonia among children . Antimicrobial resistance among pneumococci has increased in recent years and complicates treatment . The introduction of heptavalent pneumococcal conjugate vaccine (PCV7) could reduce acquisition of antimicrobial-resistant pneumococci . METHODS: We obtained 1350 nasopharyngeal swabs for culture from 1275 children aged 3-59 months presenting at 3 clinics in Anchorage, Alaska, during the winters of 2000, 2001, and 2002, as PCV7 was being introduced into the routine immunization schedule . We recorded the frequency of use of antibiotics as well as the dates of doses of PCV7 for enrolled children . We used multivariate logistic regression modeling to identify independent risk factors for overall carriage of pneumococci and carriage of PCV7-type pneumococci, cotrimoxazole-nonsusceptible (COT-NS) pneumococci, or penicillin-nonsusceptible (PCN-NS) pneumococci . RESULTS: The proportion of children who were up-to-date for age, with respect to PCV7 vaccination, increased from 0% in 2000 to 55% in 2002 . Carriage of PCV7-type pneumococci decreased by 43% (P<.0001) . Risk of carriage of PCV7-type pneumococci was lower in 2002 than in 2000, independent of vaccination status, suggesting an indirect effect of vaccination . Carriage of COT-NS, but not PCN-NS, pneumococci also decreased (38%; P=.02), not only among vaccinated children but also among unvaccinated children without recent use of antibiotics . CONCLUSIONS: Introduction of PCV7 into the routine infant immunization schedule in a community with a high prevalence of antimicrobial-resistant pneumococci appears to reduce transmission of PCV7 vaccine serotypes and COT-NS pneumococci but has no impact on overall carriage of pneumococci or carriage of PCN-NS pneumococci.

Caries Res, 2004 Nov-Dec, 38(6), 530 - 6
The photo-activated antibacterial action of toluidine blue O in a collagen matrix and in carious dentine; Williams JA et al.; The main aim of this study was to determine the susceptibility to photo-activated disinfection (PAD) of Streptococcus mutans when the organism was present in a collagen matrix--an environment similar to that which would exist within a carious tooth . In addition, the susceptibility to PAD of bacteria present in carious human teeth was also determined . Light was delivered to the collagen and teeth using a system comprising a 0.8-mm diameter isotropic tip emitting light at 633 +/- 2 nm . A single concentration of TBO (10 microg/ml) was used with both collagen and dentine . Two contact times, 30 and 180 s, were evaluated in intact collagen and additionally, for 180 s only, in collagen partially disrupted by shredding . The effect of energy doses from 1.8 to 14.4 J on the kills attained was assessed by determining the number of surviving viable bacteria . In carious dentine, two contact times, 30 and 60 s and one energy dose, 4.8 J, were used . Antibacterial effects were less than those obtained using planktonic suspensions with a maximum mean log reduction of 1.4 in shredded collagen and dentine . Increasing contact time increased the antibacterial effectiveness in both substrates although this was not always of statistical significance . Shredding the collagen resulted in significantly increased bacterial kills compared to those obtained in intact collagen for the 30-second contact time . The collagen matrix appeared to be a suitable model for carious dentine with advantages of availability and reproducibility . The results of this study have shown that PAD can achieve appreciable kills of oral bacteria, including S . mutans, when the organisms are embedded in a collagen gel or are present in carious teeth . 2004 S . Karger AG, Basel.

J Clin Microbiol, 2004 Nov, 42(11), 4980 - 7
Prevalence and molecular analysis of macrolide and fluoroquinolone resistance among isolates of Streptococcus pneumoniae collected during the 2000-2001 PROTEKT US Study; Brown SD et al.; The PROTEKT US (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin in the United States) surveillance program was established to determine the prevalence and mechanisms of antibacterial resistance among bacterial pathogens from patients with community-acquired respiratory tract infections . In year 1 of the PROTEKT US study, 10,103 isolates of Streptococcus pneumoniae, including 3,133 erythromycin-resistant strains and 81 levofloxacin-resistant strains, were collected from 206 centers . We report on the molecular analyses of these resistant strains . The resistance genotypes among the 3,044 typed macrolide-resistant isolates overall were mef(A) (n = 2,157; 70.9%), erm(B) (n = 530; 17.4%), mef(A) erm(B) (n = 304; 10.0%), and erm(A) subclass erm(TR) (n = 5; 0.2%) . Fifty (1.6%) macrolide-resistant isolates were negative for the mef and the erm resistance genes . Seventy-eight (96.3%) of the 81 levofloxacin-resistant isolates analyzed possessed multiple mutations in the gyrA, gyrB, parC, and/or parE quinolone resistance-determining regions . A total of 43 known multilocus sequence typing (MLST) profiles (or single- or double-locus variants) accounted for 75 of 81 isolates . There was no evidence of dissemination of fluoroquinolone-resistant clones within the United States; however, 12 isolates with the same MLST profile were located in one center in Massachusetts . Almost 90% of the erythromycin-resistant isolates and approximately one-third of the levofloxacin-resistant isolates were multidrug resistant.

J Clin Microbiol, 2004 Nov, 42(11), 4925 - 30
Development of a PCR method for rapid identification of new Streptococcus mutans serotype k strains; Nakano K et al.; In a previous study, we isolated and characterized a new serotype k of Streptococcus mutans from human blood and oral cavities . Analysis of the genes involved in biosynthesis of the serotype-specific polysaccharide of serotype k strains revealed that the serotype k-specific nucleotide alignment was commonly present in the 5' region of the rgpF gene (350 bp from the initial sequence) compared to the reference strains, and then a method for rapid identification of serotype k strains was developed by use of PCR with primers designed on the basis of the sequence of the variable region . PCR assays with primers specific for amplification of serotype k strains showed a negative reaction with serotype c, e, and f strains and a positive reaction with serotype k strains, with the sensitivity for identification of the serotype k strains shown to range from 5 to 50 cells . Next, the frequency of positive reactions for serotype k-specific primers was surveyed with DNA taken from saliva samples from 200 subjects (2 to 18 years of age), and 10 of those showed a positive reaction, which was higher than the frequency in our previous survey with a serological method . In addition, all saliva samples from subjects with serotype k strains in our previous study were shown to be positive with the serotype k-specific primers . These results indicate that this new PCR method is effective for identification of subjects with S . mutans serotype k.

Science, 2004 Nov 5, 306(5698), 1037 - 40
Autophagy defends cells against invading group A Streptococcus; Nakagawa I et al.; We found that the autophagic machinery could effectively eliminate pathogenic group A Streptococcus (GAS) within nonphagocytic cells . After escaping from endosomes into the cytoplasm, GAS became enveloped by autophagosome-like compartments and were killed upon fusion of these compartments with lysosomes . In autophagy-deficient Atg5-/- cells, GAS survived, multiplied, and were released from the cells . Thus, the autophagic machinery can act as an innate defense system against invading pathogens.

Fam Pract, 2004 Dec, 21(6), 599 - 604 Epub 2004 Dec.
Patient-clinician agreement on signs and symptoms of 'strep throat': a MetroNet study; Xu J et al.; BACKGROUND: Despite substantial use of the telephone in health care, only a few studies have formally evaluated the appropriateness of telephone-based management for acute medical problems . The accuracy of patients' report of signs and symptoms remains unknown . OBJECTIVE: We compared the agreement between patient self-assessment and clinician assessment on the typical signs and symptoms of group A beta-haemolytic Streptococcus (GABHS) to investigate the potential difficulties of using patient self-report to triage sore throat patients . METHODS: In this cross-sectional study, each of 200 adult pharyngitis patients was instructed to examine him/herself and to record the symptoms and physical findings . Two clinicians independently interviewed and examined each patient and recorded their findings . Each patient then had a rapid GABHS antigen test, the results of which were blinded to both clinicians and patients . Each patient self-assessment was compared with the findings of each clinician, and the agreement and disagreement between them computed . RESULTS: We found varying levels of agreement (kappa=-0.05 to 0.71) between patients and clinicians on sore throat history and physical assessments . Importantly, there was fair to substantial agreement (kappa=0.20-0.71) on the key signs and symptoms used in GABHS clinical prediction rules . As expected, history items had the highest agreement (kappa=0.52-0.71) . Patients were more likely than clinicians to report rather than deny a specific physical sign . CONCLUSION: Adult sore throat patients may reliably report their symptoms, but may not be able to assess and report accurately on relevant physical signs of pharyngitis . Patients have a tendency to over-report physical signs . This study indicates the potential difficulties associated with telephone triage of sore throat patients, or other illnesses that require assessment of physical signs.

Child Care Health Dev . 2004 Nov;30(6):729.
Dyskinesias and associated psychiatric disorders following streptococcal infections.
{Pharmacoeconomics of vaccinations in chronic obstructive pulmonary disease}
Slominski JM, Kubiak A.

Klinika Pneumonologii Katerdy Pneumonologii i Alergologii Akademii Medycznej w GdanskuIn this study basic types of pharmacoeconomics analysis are presented . Selected publications concerned influenza vaccinations in risk groups have been discussed . In age groups higher then 65 years costs of treatment are connected with rates of complications and hospitalisations . In COPD patients' pharmacoeconomic analysis shows positive results in more advanced age-groups . In Str . pneumoniae vaccination 23-valent vaccines are more clinically effective . COPD patients Streptococcus pneumoniae vaccination give better pharmacoeconomic results in higher age-groups.

Otolaryngol Head Neck Surg, 2004 Nov, 131(5), 563 - 72
The effects of superoxide dismutase in gerbils with bacterial meningitis; Ge NN et al.; BACKGROUND: Inflammatory products, such as oxygen radicals generated during the course of bacterial meningitis, can damage nerve endings, hair cells, and/or supporting cells in the cochlea . Superoxide dismutase (SOD), an O2-scavenger, has been shown to play an important role in the protection against radical toxicity in various animal experiments . OBJECTIVE: To study the antioxidant effects of SOD on the inflammatory response of gerbils with bacterial meningitis . STUDY DESIGN: Meningitis was induced in three groups of 10 gerbils by intrathecal (IT) injection of Streptococcus pneumoniae into the cisterna magna . Group 1 received IT SOD, group 2 received intramuscular (IM) SOD, and group 3, the control group, received IM normal saline . Histologic data and auditory brainstem responses (ABR) were obtained from each gerbil . RESULTS: Fibrosis and/or neo-ossification were near absent in the IT SOD group and significantly less fibrosis occurred in the IM group (IT vs . IM: P = 0.010; IT vs . control group: P = 0.001) . The amount of surviving spiral ganglion cells correlated inversely with the extent of fibrosis (r = -0.753, P < 0.00001) . CONCLUSIONS: IT injection of SOD significantly reduced cochlear fibrosis and neo-ossification, reduced the spiral ganglion cell loss, and decreased damage of the cochlear components following bacterial meningitis.

J Biol Chem, 2004 Dec 17, 279(51), 52820 - 3 Epub 2004 Nov 01.
alpha2-Macroglobulin-proteinase complexes protect Streptococcus pyogenes from killing by the antimicrobial peptide LL-37; Nyberg P et al.; The significant human bacterial pathogen Streptococcus pyogenes expresses GRAB, a surface protein that binds alpha(2)-macroglobulin (alpha(2)M), a major proteinase inhibitor of human plasma . alpha(2)M inhibits proteolysis by trapping the proteinase, which, however, still remains proteolytically active against smaller peptides that can penetrate the alpha(2)M-proteinase complex . Here we report that SpeB, a cysteine proteinase secreted by S . pyogenes, is trapped by alpha(2)M bound to protein GRAB . As a consequence, SpeB is retained at the bacterial surface and protects S . pyogenes against killing by the antibacterial peptide LL-37.

Int J Antimicrob Agents, 2004 Nov, 24(5), 485 - 90
Severity scoring in community-acquired pneumonia caused by Streptococcus pneumoniae: a 5-year experience; Ioachimescu OC et al.; Multiple severity scoring systems have been devised and evaluated in community-acquired pneumonia (CAP), but a simplified set of prognostic indicators has not yet been developed . Streptococcus pneumoniae is the most frequent aetiological agent of CAP . Our aim was to characterise the outcome in the light of different severity scoring systems and to compare the predictive values of different sets of clinical parameters, using available clinical data for pneumococcal CAP patients . This is a case series retrospective analysis that included consecutive adult pneumococcal CAP patients admitted to Danbury Hospital between 1 January 1996 and 31 December 2000 . The aetiology was confirmed by positive sputum and/or blood cultures . The severity assessment included the Pneumonia Outcome Research Trial (PORT) and British Thoracic Society (BTS) scoring systems and other additional parameters . Primary end-points were in-hospital CAP-attributable deaths and length of hospitalisation . N = 151 patients with S . pneumoniae CAP were identified . The mean (+/- standard deviation) age at the time of diagnosis was 68 (+/-15) years . Thirty-three patients (22%) were admitted to the medical intensive care unit . The mean (median) hospitalisation duration was 7.5 (+/-5) days . Door-to-antibiotic mean (median) administration time was 3.7 (2) hours . Most frequent antibiotics used initially were cephalosporins plus/minus macrolides or fluoroquinolones . The mean (+/- standard deviation) PORT score was 105 (+/-37) . The observed CAP-related mortality was 9/151 (5.9%, 95% confidence interval: 3-9%) . The mortality rate in ICU was 18% (6/33) . Sixty-nine patients (45%) had S . pneumoniae bacteraemia an admission . The bacteraemic and non-bacteraemic patients had similar PORT scores (107 vs . 104, P = 0.66), length of hospitalisation (8 vs . 7 days, P = 0.41) and mortality rates (9% vs . 4%, P = 0.30) . In conclusion, patients admitted with pneumococcal CAP, although severe and with multiple co-morbidities had low in-hospital mortality rates and lengths of hospitalisation . Neither prior antimicrobial use (or failure) nor antimicrobial resistance contributed to an adverse outcome . S . pneumoniae bacteraemia failed to correlate with need for ICU, length of stay, higher morbidity index or fatal outcome . Low rates of empirical antibiotic use for non-bacterial infections in the local community, implementation of an emergency department protocol for CAP therapy, early recognition of higher risk patients and placement in ICU, use of broad spectrum antibiotics, infectious disease approval or critical pathway restriction for admission orders, could all have combined to effect a good outcome for these patients.

Int J Antimicrob Agents, 2004 Nov, 24(5), 479 - 84
Pharmacodynamic target attainment analysis against Streptococcus pneumoniae using levofloxacin 500 mg, 750 mg and 1000 mg once daily in plasma (P) and epithelial lining fluid (ELF) of hospitalized patients with community acquired pneumonia (CAP); Noreddin AM et al.; The pharmacokinetics and pharmacodynamics of levofloxacin in patients with respiratory infections such as community-acquired pneumonia (CAP) are poorly documented . This work aimed at assessing the pharmacodynamic target attainment against Streptococcus pneumoniae using levofloxacin 500 mg, 750 mg and 1000 mg administered once daily in plasma (P) and epithelial lining fluid (ELF) of hospitalized patients with community acquired pneumonia . The pharmacokinetics of levofloxacin in elderly (>/=65 years) compared with younger patients (<65 years) hospitalized with CAP were simulated . Susceptibility data with S . pneumoniae from our ongoing national surveillance study (Canadian Respiratory Organism Susceptibility Study-CROSS) were then used to produce pharmacodynamic indices of AUC(0-24)/MIC(all.) Monte Carlo simulations were then used to analyse target attainment of levofloxacin using doses of 500 mg, 750 mg and 1000 mg once daily to achieve free drug AUC(0-24)/MIC(all) >/= 30-100 versus S . pneumoniae in patients with CAP . Pharmacokinetics of levofloxacin simulated after 500 mg, 750 mg and 1000 mg once daily dosing resulted in levofloxacin volume of distribution: elderly patients = younger patients, while levofloxacin clearance was: elderly patients < younger patients . Levofloxacin t(1/2) values were longer in elderly patients (9.8 +/- 2.5h) than younger patients with CAP (7.4 +/- 2.5h) . Free levofloxacin AUC(0-24) as well as AUC(0-24)/MIC(all) for S . pneumoniae were higher in elderly patients than younger patients . Monte Carlo simulation using levofloxacin 500 mg yielded probabilities of achieving free-drug AUC(0-24)/MIC(all) of 30 in P and ELF (95.7% and 98.1%) in elderly and younger patients (72.7% and 80.6%) respectively . Levofloxacin 750 mg and 1000 mg once daily had probability of achieving free-drug AUC(0-24)/MIC(all) of 30 in P/ELF of 98.1%/98.6% and 99.2%/99.0%, respectively, in elderly patients compared with 89.9%/94.1% and 95.2%/96.5%, respectively, for younger patients . Probability of achieving of AUC(0-24)/MIC(all) of 100 in P or ELF was very low in both patient populations at different doses except in the case of elderly patients receiving levofloxacin in a dose of 1000 mg once daily P/ELF of 78.5%/87.0% . We conclude that levofloxacin pharmacokinetics in elderly patients with CAP are markedly different from those of younger patients . Levofloxacin 750 mg OD provides high probabilities of achieving free-drug AUC(0-24)/MIC(all) of 30 in both plasma and epithelial lining fluid in patients with CAP including younger patients . Levofloxacin 500 mg OD provides high probabilities of achieving free-drug AUC(0-24)/MIC(all) of 30 in elderly patients with CAP, although we favour the 750 mg dosing in these patients as well . Levofloxacin 750 mg OD results in high probability of pharmacodynamic target attainment and improved bacteriological outcome against S . pneumoniae in patients with CAP.

Int J Antimicrob Agents, 2004 Nov, 24(5), 411 - 22
Community-acquired pneumonia: new management strategies for evolving pathogens and antimicrobial susceptibilities; Klugman KP et al.; Community-acquired pneumonia (CAP) is still one of the leading causes of mortality and morbidity . The most common bacterial cause of CAP is Streptococcus pneumoniae . The increase in antimicrobial resistance has raised concerns about the efficacy of available therapies, and a call for the reassessment of both existing and newer therapeutic agents . Although microbiological breakpoints are useful for monitoring the emergence of resistance, the current National Committee for Clinical Laboratory Standards (NCCLS) guidelines make no distinction between clinical and microbiological breakpoints . Recent changes in NCCLS breakpoints for extended spectrum cephalosporins have provided a more meaningful approach to susceptibility testing and to consideration of the site of infection . Further controversy surrounds the clinical guidelines relating to CAP in terms of which antimicrobial agents should be given empirically to which types of patients . Within this review, the role of monotherapy versus the need for combination antimicrobial therapy, which often includes a macrolide and an extended spectrum cephalosporin such as ceftriaxone, is discussed . This review also discusses the various aspects of antimicrobial susceptibilities of S . pneumoniae, the drivers and influences of increasing resistance, the clinical relevance of this resistance and possible therapeutic options in the face of changing susceptibilities and mixed bacterial aetiologies . New guidelines from the IDSA attempt to embrace these changes.

Plasmid, 2004 Nov, 52(3), 225 - 9
Sequence analysis of pDN571, a plasmid encoding novel bacteriocin production in M-type 57 Streptococcus pyogenes; Heng NC et al.; Production of the novel bacteriocin streptococcin A-M57 (SA-M57) by Streptococcus pyogenes strains of M-protein type 57 is plasmid-associated . Plasmid pDN571 (3351bp) harbored by S . pyogenes 71-724, the prototype M-type 57 strain, has been completely sequenced and contains three putative open reading frames (repA, scnM57 and ORF3) . In addition, the double-strand and single-strand (SSO) origins of replication were identified . Analysis of the replication-associated genetic elements places pDN571 in the ubiquitous pC194/pUB110 family of rolling-circle plasmids . The SSO of pDN571 is of the ssoA type . SA-M57 (encoded by scnM57) is synthesized as a secreted 179-amino acid polypeptide with a 27-residue secretion signal peptide and has no homology to proteins of known function.

Medicina (Kaunas), 2004, 40(10), 969 - 74
{Primary peritonitis caused by group A beta-hemolytic streptococcus}; Auskalnis S et al.; A rare case of primary peritonitis caused by group A beta-hemolytic streptococcus in previously healthy woman is presented . The entry site of infection was tonsillitis . Infection was complicated by soft-tissue infection of abdominal and thoracic wall, associated with toxic shock . Streptococcus growth was obtained in the cultures from the tonsils and blood . The patient underwent surgery: laparoscopy, laparotomy and multiple incisions in the phlegmon site . The lasting administration of penicillin caused recovery.

Biol Pharm Bull, 2004 Nov, 27(11), 1834 - 9
Comparative evaluation of in-vitro effects of Brazilian green propolis and Baccharis dracunculifolia extracts on cariogenic factors of Streptococcus mutans; Leitao DP et al.; Streptococcus mutans triggers dental caries establishment by two major factors: synthesis of organic acids, which demineralize dental enamel, and synthesis of glucans, which mediate the attachment of bacteria to the tooth surface . Propolis is a natural product that may prevent dental caries . Baccharis dracunculifolia DC (Asteraceae), a native plant from Brazil, is the most important botanical origin for the production of green propolis (Brazilian propolis) by honeybees . However, whether B . dracunculifolia (Bd) has an anticariogenic effect, like green propolis, remains unknown . Herein, we have made a comparative evaluation of the effects of extracts from green propolis and Bd on the glucan synthesis and acidogenic potential of S . mutans . The inhibitory effects of the extracts on bacterial acid production were evaluated through the potentiometric measurement of pH from bacterial suspensions treated with serial concentrations of both extracts . Besides presenting close inhibitory values at the same concentration range, Bd leaf rinse and green propolis extracts had similar IC(50) values (0.41 and 0.34 mg/ml, respectively) . Both extracts produced a bacteriostatic effect on S . mutans cultures at a concentration of 0.40 mg/ml . Estimated inhibitory values of green propolis and Bd leaf rinse extracts on the synthesis of insoluble glucans (IC(50)=12.9 and 25.0 microg/ml, respectively) and soluble glucans (IC(50)=50.4 and 49.1 microg/ml, respectively) were not significantly different from each other at p<0.05 . The results demonstrate that Bd leaf rinse and green propolis extracts have similar inhibitory effects on the S . mutans cariogenic factors evaluated herein, and allowed us to suggest that Bd leaves may be a potential source for pharmaceutical products employed for this purpose.

Eur Respir J, 2004 Nov, 24(5), 779 - 85
Severe community-acquired pneumonia: assessment of microbial aetiology as mortality factor; Paganin F et al.; Community-acquired pneumonia (CAP) remains a major cause of mortality . The aetiology of CAP has rarely been identified as a mortality risk factor . A prospective study was conducted to assess the prognostic factors of CAP patients admitted to the intensive care unit (Centre Hospitalier Departmental Felix Guyon, St Denis de la Reunion, France), with a special emphasis on microbial aetiology . All variables assessing severity were collected, with a special emphasis on microbial investigations . Among 112 immunocompetent patients (mean+/-SD age 54.7+/-15.1 yrs), 84% were male . Severity of CAP was demonstrated by mortality rate (43%), shock (48%), simplified acute physiology score (SAPS; 46.4+/-21.6) and mechanical ventilation support (82%) . Mean risk factor score was 2.2+/-1.2 . Microbiological identification was obtained in 78.6% of cases, with positive blood culture in 33% . Most frequently, microbial agents were Streptococcus pneumoniae and Klebsiella pneumoniae (42% and 22%, respectively) . The univariate analysis recorded the usual mortality variables: age, alcohol consumption, SAPS, shock, mechanical ventilation, positive end expiratory pressure level, positive blood culture, multilobar infiltrates on chest radiograph, neutropenia, and acidosis, and found K . pneumoniae (versus S . pneumoniae, and all CAP) as a mortality factor . The multivariate analysis demonstrated that septic shock (relative risk (RR) 141), K . pneumoniae CAP (RR 27), SAPS (RR 10.7) and positive blood culture (RR 2.7) were independent factors related to death . In conclusion, the present study found that the microbial aetiology, Klebsiella pneumoniae, was an independent risk factor for mortality in severe community-acquired pneumonia.

J Bacteriol, 2004 Nov, 186(22), 7601 - 9
Two distinct genotypes of prtF2, encoding a fibronectin binding protein, and evolution of the gene family in Streptococcus pyogenes; Ramachandran V et al.; The group A Streptococcus (GAS) is an important pathogen that is responsible for a wide range of human diseases . Fibronectin binding proteins (FBPs) play an important role in promoting GAS adherence and invasion of host cells . The prtF2 gene encodes an FBP and is present in approximately 60% of GAS strains . In the present study we examined 51 prtF2-positive GAS strains isolated from the Northern Territory of Australia, and here we describe two genotypes of prtF2 which are mutually exclusive . The two genotypes have been identified previously as pfbp and fbaB . We show that these genotypes map to the same chromosomal location within the highly recombinatorial fibronectin-collagen-T antigen (FCT) locus, indicating that they arose from a common ancestor, and in this study these genotypes were designated the pfbp type and the fbaB type . Phylogenetic analysis of seven pfbp types, 14 fbaB types, and 11 prtF2-negative GAS strains by pulsed-field gel electrophoresis (PFGE) produced 32 distinct PFGE patterns . Interpretation of evolution based on the PFGE dendrogram by parsimony suggested that the pfbp type had a recent origin compared to the fbaB type . A comparison of multiple DNA sequences of the pfbp and fbaB types revealed a mosaic pattern for the amino-terminal region of the pfbp types . The fbaB type is generally conserved at the amino terminus but varies in the number of fibronectin binding repeats in the carboxy terminus . Our data also suggest that there is a possible association of the pfbp genotype with sof (84.2%), while the fbaB genotype was found in a majority of the GAS strains negative for sof (90.6%), indicating that these two prtF2 subtypes may be under different selective pressures.

Drugs, 2004, 64(22), 2597 - 618
Cefditoren pivoxil: a review of its use in the treatment of bacterial infections; Wellington K et al.; Cefditoren pivoxil (Spectracef, Meiact) is a third-generation oral cephalosporin with a broad spectrum of activity against pathogens, including both Gram-positive and -negative bacteria, and is stable to hydrolysis by many common beta-lactamases . Cefditoren pivoxil is approved for use in the treatment of acute exacerbations of chronic bronchitis (AECB), mild-to-moderate community-acquired pneumonia (CAP), acute maxillary sinusitis, acute pharyngitis/tonsillitis and uncomplicated skin and skin structure infections (indications may differ between countries).In clinical trials in adults and adolescents, cefditoren pivoxil demonstrated good clinical and bacteriological efficacy in AECB, CAP, acute maxillary sinusitis, acute pharyngitis/tonsillitis and uncomplicated skin and skin structure infections and was generally well tolerated . Thus, cefditoren pivoxil is a good option for the treatment of adult and adolescent patients with specific respiratory tract or skin infections, particularly if there is concern about Streptococcus pneumoniae with decreased susceptibility to penicillin, or beta-lactamase-mediated resistance among the common community-acquired pathogens.

J Antibiot (Tokyo), 2004 Aug, 57(8), 518 - 27
In vitro and in vivo antibacterial activities of the tricyclic ketolide TE-802 and its analogs; Ono T et al.; The in vitro and in vivo antibacterial activities of tricyclic ketolides (TKs: TE-802, TE-806, TE-935, TE-943) have been compared with those of clarithromycin (CAM), azithromycin (AZM) and rokitamycin (RKM) . TKs were active against not only erythromycin (EM)-susceptible organisms; aerobic gram-positive bacteria, some gram-negative bacteria, anaerobic bacteria and Mycoplasma pneumoniae, but also EM-resistant Staphylococcus aureus (inducible macrolide-resistant strains) as well as EM-resistant Streptococcus pneumoniae (efflux-resistant strains) . The therapeutic efficacies of TKs against systemic infections and respiratory tract infection (RTI) caused by gram-positive bacteria in mice are superior to those of CAM and AZM . The peak plasma levels (Cmax, p.o.) of TE-802 in mice were equal to that of CAM, but the plasma area under the concentration-time curve (AUC(24 hours)) was 4.7 times that for CAM . The plasma Cmax (p.o.) value for TE-802 in monkey was equal to that of CAM, whereas the AUC(8 hours) value was three-fourths that of CAM . The pharmacokinetics of TE-802 are similar to those of AZM in mice and monkeys, suggesting the potential for once-daily administration in humans.

Przegl Lek, 2004, 61(5), 518 - 22
{Periodontitis and cardiovascular diseases--publications' review}; Bochniak M et al.; Nowadays periodontal diseases are treated as a one of a social diseases . The main consequences of them are: premature teeth loss and possibility of inducing, aggravating and modyfing many systemic disorders, such as endo- and myocarditis, glomerulonephritis, iriditis, retinitis, rheumatic polyarthritis . The scientific data performed in the last 10 years indicate links between periodontitis and atheromatosis, coronary heart disease and acute coronary events, including myocardial infarction . In this study reported was the epidemiological dependences between periodontal and cardiovascular disesaes . There were described hypotheses of negative influence of periodontal foci on induction and progression of inflammation in coronary vessel walls and destabilisation of atheromatous plaques, also was included theory of direct bacterial invasion and cytokine theory . There were shown results of studies which proved the presence of genetic material of main periodontal bacterial pathogens, such as Porphyromonas gingivalis and Prevotella intermedia, in atheromatous plaques in coronary arteries . There were noted other potential mechanismes of induction of acute coronary events connected with plateled aggregation induced by specific proteins secreted by Streptococcus sanguis and the role of Helicobacter pylori infection, the bacteria from periodontal pockets that is presently more often isolated . Analysing these data it was concluded, that the co-operation between cardiologists and dentists, especially the periodontologists, is necessary during the treatment of coronary heart disease . Periodontal thearapy should be included as an additional element of cardiological therapy . Education of patients is also very important for prophylaxis of cardiovascular diseases.

Clin Exp Rheumatol, 2004 Jul-Aug, 22(4 Suppl 34), S59 - 63
T and NK cell subset changes with microbial extracts and human HSP60-derived peptides in Behçet's disease; Kibaroglu A et al.; OBJECTIVE: Microorganisms such as streptococcus and autoantigens such as 60 kD heat-shock protein (HSP60) are implicated in the etiopathogenesis of Behcet's disease (BD) . METHODS: Peripheral blood mononuclear cells from patients with BD (n = 16) and healthy controls (HC) (n = 11) were cultured for 5 days with extracts of S . sanguis-KTH-1 (SS), E . coli (EC) and a mixed peptide combination from human HSP60 (aa 136-50, 179-97, 224-58 and 336-51) reported to be associated with BD . T and NK cell subset changes were determined by flow cytometry . RESULTS: In unstimulated 5-day cultures gammadelta+ (both CD4+gammadelta+ and CD8+gammadelta+), CD8+alphabeta+, CD4+CD56+ and CD8+CD11b+ cells were increased in BD compared to HC . In antigen-stimulated cultures of BD patients CD3+ and alphabeta+ T cells responded to HSP60 peptides whereas EC stimulated only CD16/ CD56+ NK cells . In the control group, similar to BD, alphabeta+ and CD4+ T cells responded to HSP60 peptides, however SS and EC mainly activated cytotoxic T cell subsets (CD8+CD11b and CD4+CD56+ T cells) . CONCLUSION: Significant increases in unstimulated T cell subsets suggest the presence of an in vivo T cell activation in BD . In both patients and controls similar patterns of responses were observed against different microorganisms, however the role of human HSP60 peptides as immunodominant, crossreactive antigens could not be demonstrated.

Anticancer Res, 2004 Sep-Oct, 24(5C), 3343 - 53
Structural analysis of human specific cytolysin intermedilysin aiming application to cancer immunotherapy; Ohkura K et al.; BACKGROUND: Intermedilysin (ILY) is a human specific cytolysin secreted by Streptococcus intermedius . In the present study, we performed molecular modeling of ILY and cholesterol-dependent cytolysins (CDCs) (pneumolysin, PLY; listeriolysin O, LLO; streptolysin O, SLO; alveolysin, ALV; suilysin, SLY; pyolysin, PLO) to compare the membrane binding domains including the undecapeptide (11mer) region which is thought to be necessary for the cytolytic activity of CDCs . MATERIALS AND METHODS: The molecular models of cytolysins were constructed using InsightII with Homology module with X-ray data of perfringolysin O (PFO) . RESULTS: The ILY molecule was long and rod shaped, and comprised four domains . ILY was shown to possess stereocomplementary surfaces within the molecule and the potential to stack with 8 degrees of curvature leading to a ring cluster of 45 molecules or so in the human erythrocyte cell membranes . CONCLUSION: From the molecular orbital calculations and isostatic potential analysis, we considered that the ILY 11mer region has different features from those of traditional CDCs, and the ILY domain 4 should be very useful to apply the human cell-specific targeting module.

Yonsei Med J, 2004 Oct 31, 45(5), 936 - 40
Subacute bacterial endocarditis associated with upper endoscopy; Cho BC et al.; Transient bacteremia associated with various endoscopic procedures is a well-documented phenomenon . Clinically important bacteremias are very rarely seen, however, this malady has significant morbidity in susceptible patients with valvular heart disease, liver cirrhosis, malignancy and immune deficiency . This bacteremia is a complication that is generally observed secondary to upper endoscopy and other associated invasive procedures in at risk patients, and the more serious manifestations include spontaneous bacterial peritonitis, septic arthritis, meningitis, brain abscess and infective endocarditis . Infective endocarditis is an extremely rare complication of gastrointestinal endoscopy, and it has been convincingly documented in only seven cases . We report a case of native valve endocarditis due to Streptococcus intermedius in a patient with valvular heart disease as a consequence of routine upper endoscopy.

Acta Otolaryngol, 2004 Nov, 124(9), 1000 - 7
Intracochlear perfusion of pneumolysin, a pneumococcal protein, rapidly abolishes auditory potentials in the Guinea pig cochlea; Skinner LJ et al.; OBJECTIVE: Bacterial meningitis and chronic suppurative otitis media caused by Streptococcus pneumoniae are associated with considerable otological morbidity . Specifically, sensorineural hearing loss is a permanent sequela in a third of those who contract pneumococcal meningitis . Pneumolysin, a pneumococcal protein, has been implicated as one of the main virulence/cytotoxic factors . Its pathogenicity is intimately dependent on an ability to form transmembrane pores on binding with cholesterol in target tissues . MATERIAL AND METHODS: We perfused wild-type pneumolysin, at a number of different concentrations, into the guinea pig cochlea and used electrocochleography to characterize the effects of this cytolytic exotoxin in the organ of Corti . RESULTS: Intracochlear perfusion of pneumolysin (10 microg/50 microl) reduced the compound action potential of the auditory nerve within seconds . The cochlear microphonics (f1=8 kHz, f2=9.68 kHz) and their distortion product (2f1-f2) were also reduced, albeit in a slightly less dramatic fashion . At lower concentrations (1 microg/50 microl), a selective and earlier effect on inner hair cells was observed . CONCLUSIONS: These results clearly show that significant ototoxicity ensues when sensory cells of the organ of Corti are exposed to pneumolysin (and complete cochlear death when the concentration is high enough) . Toxicity is dose-dependent and appears to be site-sensitive . This may have implications for any possible future protective strategies against pneumococcal disease in the ear.

Scand J Infect Dis, 2004, 36(10), 756 - 8
Severe pneumococcal meningitis heralding a deep hypogammaglobulinaemia related to common variable immunodeficiency, at the age of 27 years; Manfredi R et al.; Common variable immunodeficiency with an associated broad immunoglobulin (0.7%) deficit affecting all subclasses, was revealed in a 27-y-old previously healthy female, upon development of a severe pneumococcal meningitis . We report the third case of purulent meningitis complicating this primary immunodeficiency, and the second due to Streptococcus pneumoniae . Clinicians should maintain an elevated suspicion for congenital immunodeficiency, especially when observing adult patients with a negligible prior history.

J Obstet Gynaecol, 2000, 20(5), 460 - 4
Obstetricians' compliance with CDC guidelines on maternal screening and intrapartum prophylaxis for group B streptococcus; M Mahieu J J De Dooy E Leys L; How obstetricians' opinions regarding universal screening of pregnant woman for group B streptococcus and their attitude regarding chemoprophylaxis vary from the Centres for Disease Control (CDC) guidelines were studied, and the physician characteristics that predict divergent opinions were determined . Five hundred and eighty-two obstetricians in the Flanders region of Belgium were contacted by a postal survey . Ordinal logistic regression was used to assess obstetricians' characteristics that predict divergence.Only 44% agreed with routine prenatal screening for group B streptococcus of whom 72% would screen at 35 weeks . Intrapartum prophylaxis would be done on the basis of risk factors alone in 38% . Multivariate analysis revealed significant provincial differences (best in Antwerp, worst in West-Flanders) and increasing age was associated with decreasing compliance . It is concluded that a minority of the obstetricians believes in routine prenatal screening and one-third would give prophylaxis on the basis of risk factors alone . Obstetrician's age and province of practice predict divergent opinions.

Trop Doct, 2004 Oct, 34(4), 200 - 3
Pneumococcal infections in HIV infected adults--clinical features, reasons behind the association and future hopes for prevention; Gordon S; Streptococcus pneumoniae is the most important bacterial cause of pneumonia and meningitis among adults world wide . It is a particularly common cause of these infections and also bacteraemia among HIV infected adults with rates of disease increasing to more than 100 times the normal as HIV infection progresses to AIDS . This article briefly describes the common presentations and outcomes of pneumococcal disease (PD) in HIV infected adult inpatients in Malawi . Factors underlying susceptibility to pneumococcal infection in HIV infected adults are then reviewed, along with the effectiveness of current vaccines . Finally, novel approaches that will be needed to combat PD in HIV afflicted parts of the world are suggested.

Singapore Med J, 2004 Nov, 45(11), 525 - 9
Infective endocarditis in childhood: a seven-year experience; Liew WK et al.; INTRODUCTION: The epidemiology, clinical features, treatment and outcomes of infective endocarditis (IE) are reviewed . METHODS: A retrospective descriptive study was performed involving patients treated for IE at a paediatric tertiary centre in Singapore, between May 1997 and April 2004 . Duke criteria were used to retrospectively evaluate the diagnosis of IE in these cases . Data analysis was performed using SPSS for Windows . RESULTS: There were a total of 27 children with IE in the seven-year study period . Of these, 24 (88.9 percent) had congenital heart disease, one had rheumatic valvular heart disease and two had normal anatomy . Fever (81.5 percent) was the primary presenting symptom, while splenomegaly (40.7 percent) and septic spots (22.2 percent) were the most common physical findings . C-reactive protein was raised in all cases with a mean of 100.1mg/L . Blood cultures were positive in 77.8 percent of cases and the most common organism identified was Viridans Streptococcus species (25.9 percent) . Vegetations were detected on echocardiography in 55.5 percent of cases . According to the Duke criteria, 48.1 percent of our patients fulfilled the clinical diagnosis of definite IE and 51.9 percent had possible IE . The median duration of parenteral antibiotics was 31 days . Major complications were seen in seven (25.9 percent) patients, of whom five had either left heart vegetations or a right-to-left shunt physiology . CONCLUSION: IE is an uncommon infection in childhood and occurs primarily in patients with congenital heart disease . Rheumatic heart disease is rarely a predisposing cause in our local children . Early diagnosis of IE is challenging and depends on a high index of suspicion . Useful clues include the presence of splenomegaly, septic emboli, microscopic haematuria and high C-reactive protein level greater than 100mg/L . The Duke criteria for the diagnosis of IE are relevant locally, but if modified with an expanded list of minor criteria including the above useful clues, may increase the sensitivity of diagnosing definite IE . The presence of left-sided heart vegetations is a strong predictor of complications and must be treated aggressively.

Neurosurgery, 2004 Nov, 55(5), 1154 - 1162
Direct Detection of Bacterial Pathogens in Brain Abscesses by Polymerase Chain Reaction Amplification and Sequencing of Partial 16S Ribosomal Deoxyribonucleic Acid Fragments; Tsai JC et al.; OBJECTIVE: To evaluate the feasibility of detecting bacterial pathogens directly from the clinical brain abscess specimens by polymerase chain reaction (PCR) amplification and sequencing of bacterial 16S ribosomal deoxyribonucleic acid (rDNA) . METHODS: A total of 14 specimens were tested by both culture and PCR amplification, targeting the full-length or a partial region of 16S rDNA . 16S rDNA is known to be conserved in bacteria . Sequencing of partial-length and full-length 16S rDNA was performed . The sequence data were compared with known sequences of 16S rDNA in the National Center for Biotechnology Information GenBank by using the Basic Local Alignment Search Tool (BLAST) algorithm . The species with the best match of similarity were regarded as the pathogenic species in the samples . We also developed a Streptococcus-specific multiplex PCR analysis for identifying members of the Streptococcus species, the most common pathogen of brain abscesses . RESULTS: The 10 culture-positive specimens were all PCR-positive for partial 16S rDNA, but only seven were positive for full-length 16S rDNA amplification . Bacterial DNA was not detected in the remaining four specimens with a negative culture . Species identification by phenotypes from culture was in agreement with that by sequencing results of partial-length (or full-length) 16S rDNA . The Streptococcus-specific PCR analysis could detect Streptococcus species correctly in one step . CONCLUSION: Bacterial 16S rDNA sequences provide reliable clues to the identification of unknown pathogens . PCR analysis of 16S rDNA and sequencing may identify pathogens to the species level directly from brain abscesses . This approach is rapid and is useful especially in the identification of slow-growing and fastidious organisms.

J Ethnopharmacol, 2004 Dec, 95(2-3), 353 - 7
Studies on antibacterial, antioxidant and fibroblast growth stimulation of wound healing remedies from South Africa; Steenkamp V et al.; Aqueous and methanol extracts of Urtica urens, Capparis tomentosa, Dicoma anomala, Leonotis leonorus, Xysmalobium undulatum, Helichrysum foetidum, Pterocarpus angolensis, Terminalia sericea and Gunnera perpensa, plants documented as being used for topical wound healing in the literature, were tested for antibacterial activity against Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli and Pseudomonas aeruginosa . Methanol and water extracts of two of these plants, Terminalia sericea and Gunnera perpensa, were more active compared to the other extracts against Streptococcus pyogenes and Staphylococcus aureus . The effects of the latter plants on fibroblast growth as well as oxidant production by N-formyl-methionyl-leucyl-phenylalanine were also studied . The water and methanol extracts of Terminalia sericea and Gunnera perpensa significantly decreased luciginin enhanced chemiluminescence at concentrations of 100 microg/ml and higher . However, the extracts had no effect on the growth of primary human fibroblasts.

Wien Klin Wochenschr, 2004, 116 Suppl 2, 87 - 9
Brain abscess after milk tooth self-extraction; Strojnik T et al.; Brain abscesses are rare, especially in children, but they can be life-threatening infections . To date, dental pathology has been linked to only a small number of brain abscesses . To our best knowledge this is the first reported case of a brain abscess following self-extraction of a milk tooth . We are reporting on a 12-year-old previously healthy boy who developed a brain abscess in the vicinity of the left precentral gyrus . Clinical examination prior to surgery showed a severe right hemiparesis, more pronounced in his leg . We performed an ultrasonographically guided puncture and aspiration of the abscess through a small craniotomy . Immediately after the procedure he became hemiplegic . Bacteriological examination of the aspirated pus revealed Streptococcus intermedius, Streptococcus beta-haemolyticus group F, Fusobacterium species and gram-negative rods . The same species of microorganisms were identified in a smear from the vicinity of the extracted tooth . The patient was carefully screened for possible other sources of infection, but none was found . Following appropriate antimicrobial treatment he recovered completely and returned home without any neurological deficit.

Semin Arthritis Rheum, 2004 Oct, 34(2), 559 - 69
Septic arthritis in the adult caused by Streptococcus pneumoniae: a report of 4 cases and review of the literature; Raad J et al.; OBJECTIVES: To identify coexistent diseases, clinical features, approaches to management, and predictors of outcome in patients with pneumococcal septic arthritis . METHODS: Case series of 4 adults with Streptococcus pneumoniae septic arthritis seen at a university hospital, plus a review of 115 adults with pneumococcal septic arthritis reported in the medical literature from 1973 through 2003 . RESULTS: Among our 4 patients, 3 had polyarticular infections, joint prostheses were involved in 1, 3 had underlying joint diseases, and 1 had concurrent meningitis . Infection was caused by penicillin-intermediate/cephalosporine-susceptible S pneumoniae in 1 patient and penicillin-resistant/cephalosporine-intermediate S . pneumoniae in 1 patient . After a mean treatment duration of 6 weeks, all patients were clinically cured of infection . Review of the literature identified 115 cases of S pneumoniae septic arthritis in adults . Clinical data were available for 107 patients . Twenty-nine cases were polyarticular (26%), joint prostheses were involved in 15 patients (13%), and 61 patients had underlying joint disease (57%) . Meningitis was a concurrent infection in 15 cases . The presumed primary focus of infection was the respiratory tree in 44 patients . Ninety-six percent of cases were caused by penicillin-susceptible organisms . Cure of infection with survival was achieved in 83% (79 of 95) of patients with native joint septic arthritis and in 67% (8 of 12) of patients with prosthetic joint infection . A good functional outcome (full range of motion or return to baseline range of motion) after infection was achieved by 44 of 71 patients (62%) with native joint infection and by 4 of 7 patients (57%) with infections of prosthetic joints . The likelihood of cure of infection or good functional outcome was not influenced by method of joint drainage . CONCLUSIONS: S pneumoniae is an uncommon, but not rare, cause of septic arthritis in the adult . Many patients have underlying joint disease (especially rheumatoid arthritis) and coexistent alcoholism . Although most infections involve native joints, prosthetic joint infections comprise 13% of cases . Polyarticular disease occurs in approximately one quarter of patients . Most patients have a preceding or concurrent extra-articular focus of pneumococcal infection . To date, the majority of reported infections are caused by penicillin-susceptible organisms, so penicillin G or a third-generation cephalosporine such as ceftriaxone remains the appropriate treatment option . However, infection with drug-resistant organisms is likely to be an increasing problem in the future . With directed antimicrobial therapy and appropriate joint drainage, the outcome is generally good for patients with native joint infections . In contrast, only two thirds of patients with infections of prosthetic joints survive their infections . Approximately 40% of surviving patients experience functional impairment or chronic pain as a sequelae of their infection.

Antimicrob Agents Chemother, 2004 Nov, 48(11), 4444 - 6
Antibiotic susceptibility in neonatal invasive isolates of Streptococcus agalactiae in a 2-year nationwide surveillance study in Germany; Fluegge K et al.; The antimicrobial susceptibility of 296 invasive neonatal group B streptococcus isolates from a nationwide 2-year surveillance study in Germany was investigated . All isolates were susceptible to beta-lactams, linezolid, quinupristin-dalfopristin, and vancomycin . Erythromycin and clindamycin resistance was found in 10.1 and 5.7%, respectively . The ermB, ermTR, or mefA gene was detected in all but one of the erythromycin-resistant isolates.

Antimicrob Agents Chemother, 2004 Nov, 48(11), 4144 - 7
Effects of amoxicillin subinhibitory concentrations on the cross-protection developed by pneumococcal antibodies in mouse sepsis caused by an amoxicillin-resistant serotype 6B Streptococcus pneumoniae strain; Tarrago D et al.; A model of mouse sepsis caused by a serotype 6B Streptococcus pneumoniae strain (amoxicillin MIC of 8 microg/ml) was developed to investigate the therapeutic effect of an amoxicillin dose (3.12 mg/kg of body weight three times daily for 48 h) producing, over the whole treatment period, subinhibitory concentrations in serum (peak concentration {C(max)}: 6.1 microg/ml) in animals that prior to infection had been passively immunized with a 6B or 23F hyperimmune serum (obtained by immunization with a whole-cell heat-inactivated inoculum and diluted to produce no protective effect by itself) . Mortality in nonimmunized animals treated with antibiotic (3.12 mg/kg) was 90%, and mortality in animals immunized but not treated with the antibiotic was 100% . Antibiotic treatment in immunized animals produced mortality rates </=20% when the hyperimmune serum was used, thus showing cross-protection and synergism (defined as the situation in which there is no response to the single agents {no differences versus placebo} while the combination exhibits significant activity) with subinhibitory concentrations of the antibiotic . The presence of antipneumococcal antibodies allowed antibiotic efficacy with negligible values of pharmacodynamic parameters (C(max)/MIC ratio of <1 and thus a null value for the time that serum levels exceed the MIC) . This in vivo synergism offers a potential therapeutic strategy against resistant strains.

Turk J Pediatr, 2004 Jul-Sep, 46(3), 208 - 13
Defective anti-polysaccharide antibody response in patients with ataxia-telangiectasia; Sanal O et al.; The immunodeficiency in ataxia-telangiectasia (A-T) patients involves both cellular and humoral immunity; however, the specific antibody response is not well defined . Frequent respiratory infections are a prominent feature in A-T . Streptococcus pneumoniae is a common pathogen responsible for these infections . Defective B cell membrane signaling has been reported in A-T cells . These observations prompted us to investigate the B cell response to six frequently encountered pneumococcal serotypes in A-T patients . We found defective IgG antibody production to all studied serotypes (3, 6B, 7F, 14, 19F, and 23F) in 22 of 31 A-T patients (71%) who were immunized with a polyvalent pneumococcal vaccine . The impaired antibody responses did not correlate with either history of infection or serum immunoglobulin isotype levels . In addition, we did not observe any correlation between the pneumococcal antibody production and a specific mutation or level of intracellular ATM (ataxia-telangiectasia mutated) protein in lysates of lymphoblastoid cell lines from these patients . Our results suggest that the extent and severity of the recurrent sinopulmonary infections may depend not only on the immunological defects but also on other ATM-dependent physiological responses.

Intensive Care Med, 2005 Jan, 31(1), 146 - 50 Epub 2004 Oct 16.
Dexamethasone decreases neurological sequelae and caspase activity; Irazuzta J et al.; OBJECTIVE: To evaluate the use of dexamethasone in a model of meningitis-induced brain injury . Changes in neurobehavioral performance were the primary outcome variables . Changes in caspase activation and markers of neuronal injury were the secondary outcome variables.DESIGN: Randomized, prospective animal study.SETTING: University research laboratory.SUBJECTS: Male Wistar rats.INTERVENTIONS: Animals underwent a basilar cistern injection of either placebo or a suspension of Group B Streptococcus . Sixteen hours after inoculation, animals were randomized and received either dexamethasone or placebo in addition to antibiotics . Neurobehavioral performance and biological markers of brain injury were assessed at 3 days and 9 days after randomization . In a second experiment, caspase 1 and 3 were evaluated at 6 h, 24 h, and 72 h after dexamethasone administration.MEASUREMENTS AND MAIN RESULTS: Neurobehavioral performance at 3 days and 9 days was significantly improved in the dexamethasone group . Serum C-tau and cerebral edema were decreased after 3 days of dexamethasone treatment . Dexamethasone decreased Caspase 3 activation in meningitic animals.CONCLUSION: These findings demonstrate that dexamethasone decreases acute brain injury in a rat model of bacterial meningitis as measured by preservation of neurobehavioral performance.

Microbiol Immunol, 2004, 48(10), 779 - 82
Consideration of cysteine protease activity for serological M-typing of clinical Streptococcus pyogenes isolates; Morita M et al.; Clinical isolates of Streptococcus pyogenes were classified by serological typing of their surface M protein . Non-M typeable strains with the emm1 gene were characterized as the degradation of M protein caused by overproduction of the extracellular cysteine protease, SpeB . These events are dependent on the growth phase . M protein produced prior to expression of SpeB is degraded in the stationary phase when the active form of SpeB is detected . The proteolytic degradation of M protein should be considered for precise M typing analysis.

Infect Immun, 2004 Nov, 72(11), 6748 - 52
Streptococcus mutans surface alpha-enolase binds salivary mucin MG2 and human plasminogen; Ge J et al.; Matrix-assisted laser desorption ionization-time of flight mass spectrometry analysis identified enolase as a cell surface component of Streptococcus mutans, which was confirmed by enzyme-linked immunosorbent assay, Western blotting, and transmission electron microscopy . Surface enolase was demonstrated to bind to human plasminogen and salivary mucin MG2 . The results suggested a role for enolase in S . mutans attachment, clearance, or breach of the bloodstream barrier.

Infect Immun, 2004 Nov, 72(11), 6694 - 8
Streptococcus pneumoniae-induced inhibition of rat ependymal cilia is attenuated by antipneumolysin antibody; Hirst RA et al.; Ciliated ependymal cells line the ventricular surfaces and aqueducts of the brain . In ex vivo experiments, pneumolysin caused rapid inhibition of the ependymal ciliary beat frequency and caused ependymal cell disruption . Wild-type pneumococci and pneumococci deficient in pneumolysin caused ciliary slowing, but penicillin lysis of wild-type, not pneumolysin-deficient, pneumococci increased the extent of ciliary inhibition . This effect was abolished by antipneumolysin antibody . Ependymal ciliary stasis by purified pneumolysin was also blocked by the addition of antipneumolysin monoclonal antibodies . These data show that antibiotic lysis of Streptococcus pneumoniae can be detrimental to the ciliated ependyma and that antipneumolysin antibody may have a therapeutic potential.

Infect Immun, 2004 Nov, 72(11), 6689 - 93
Moraxella catarrhalis coaggregates with Streptococcus pyogenes and modulates interactions of S . pyogenes with human epithelial cells; Lafontaine ER et al.; The pathogens Streptococcus pyogenes and Moraxella catarrhalis colonize overlapping regions of the human nasopharynx . We have found that M . catarrhalis can dramatically increase S . pyogenes adherence to human epithelial cells and that species-specific coaggregation of these bacteria correlates with this enhanced adherence.

Infect Immun, 2004 Nov, 72(11), 6528 - 37
The Streptococcus gordonii surface proteins GspB and Hsa mediate binding to sialylated carbohydrate epitopes on the platelet membrane glycoprotein Ibalpha; Bensing BA et al.; Platelet binding by Streptococcus gordonii strain M99 is dependent on expression of the cell wall-anchored glycoprotein GspB . This large cell surface protein is exported from the M99 cytoplasm via a dedicated transport system that includes SecA2 and SecY2 . GspB is highly similar to Hsa, a protein expressed by S . gordonii Challis that has been characterized as a sialic acid binding hemagglutinin . In this study, we compared the contribution of GspB and Hsa to the adherence of S . gordonii to selected glycoproteins . Our results indicate that GspB can mediate binding to a variety of sialylated glycoproteins . GspB facilitates binding to carbohydrates bearing sialic acid in either alpha(2-3) or alpha(2-6) linkages, with a slight preference for alpha(2-3) linkages . Furthermore, GspB readily mediates binding to sialic acid residues on immobilized glycocalicin, the extracellular portion of the platelet membrane glycoprotein (GP) Ibalpha (the ligand binding subunit of the platelet von Willebrand factor receptor complex GPIb-IX-V) . Although Hsa is required for the binding of S . gordonii Challis to sialic acid, most of the Hsa expressed by Challis is retained in the cytoplasm . The deficiency in export is due, at least in part, to a nonsense mutation in secA2 . Hsa export can be enhanced by complementation with secA2 from M99, which also results in significantly greater binding to sialylated glycoproteins, including glycocalicin . The combined results indicate that GspB and Hsa contribute similar binding capabilities to M99 and Challis, respectively, but there may be subtle differences in the preferred epitopes to which these adhesins bind.

Acta Odontol Latinoam, 2003, 16(1-2), 9 - 16
Low and high molecular weight chitosans interactions with Streptococcus mutans: an in vitro study; Virga C et al.; We evaluated the in vitro capacity of high and low molecular weight chitosans (HMWCh and LMWCh) to inhibit the adherence of strains of S . mutans obtained from the American Type Culture Collection (ATCC,25175) to artificial saliva-coated hydroxiapatite beads . The effect of these biopolymers was assessed in terms of pH, ionic force, minimum inhibitory concentration (MIC) and antibacterial activity . The results show that HMWCh is modified by a rise in pH (7.0) and ionic strength . The induced conformational changes lead to the formation of rigid meshes capable of aggregating and entrapping S . mutans . This process is associated to the properties of HMWCh . LMWCh gave rise to smaller aggregates that exhibited a comparatively reduced interaction capacity . The MIC for HMWCh was 0.5 g% and evidenced the bacteriostatic action of the aggregates . We conclude that HMWCh would exert an inhibitory effect on the process of specific adsorption of S . mutans to saliva-coated hydroxiapatite beads.

Acta Paediatr, 2004 Oct, 93(10), 1334 - 9
Clinical features and epidemiology of septicaemia and meningitis in neonates due to Streptococcus agalactiae in Copenhagen County, Denmark: a 10 year survey from 1992 to 2001; Andersen J et al.; AIM: To elucidate the clinical and biochemical features, and to estimate the incidence and outcome of invasive culture-verified group B streptococcal (GBS) septicaemia/meningitis in neonates in Denmark . METHODS: Clinical microbiology laboratory records in patients 0-3 mo of age were searched for culture-verified GBS during 1992-2001 in Copenhagen County . Clinical records at the neonatal intensive care unit were reviewed retrospectively . Selected clinical and biochemical parameters were evaluated . RESULTS: 61 neonates had culture-verified GBS septicaemia/meningitis . The mean annual incidence was 0.76 cases per 1000 livebirths (range 0.0-1.91) . A significant decrease in incidence was observed in the latest 3 y . The male:female ratio was 1.3:1 . Eighty percent of the neonates had early-onset GBS within 24 h, 57% with symptoms at birth . Predominant initial symptoms were respiratory (72%), cardiovascular (69%) and neurological (63%) . Only 4% developed GBS by day 7-90 . Seventy-five percent had maternal or neonatal risk factors for early-onset GBS disease; 21% had clinical asphyxia, 37% of the mothers had premature rupture of membranes and 31% of the mothers were febrile . Initial C-reactive protein (CRP) was low, but increased significantly after more than 12 h duration of symptoms in 82% of patients . Leucopenia was an important initial haematological marker . CONCLUSION: The incidence of early-onset GBS has decreased significantly in Denmark, probably because of preventive measures in pregnancy and during birth . Respiratory symptoms are early signs of early-onset GBS . Initial leucopenia and a late (12-48 h) increase in CRP are valuable markers for invasive GBS.

J Infect Dis, 2004 Nov 15, 190(10), 1762 - 6 Epub 2004 Oct 13.
Azithromycin modulates murine immune responses to pneumococcal conjugate vaccine and inhibits nasal clearance of bacteria; Fernandez AD et al.; Macrolide antibiotics, including azithromycin, have been implicated in the modulation of host immune responses, independently of their antimicrobial properties . The present work was designed to study the effect that azithromycin has on protective humoral immune responses induced by a 7-valent, polysaccharide, pneumococcal conjugate vaccine (PCV7) . By use of a murine vaccination/challenge model, it was found that inoculation with azithromycin led to significantly lower primary antibody responses, decreased recall proliferative responses, and, in nasal cavities, impaired clearance of Streptococcus pneumoniae serotype 14 from the nasal cavities . The results demonstrate that azithromycin can be inhibitory with regard to protective immune responsiveness.

J Infect Dis, 2004 Nov 15, 190(10), 1758 - 61 Epub 2004 Oct 07.
Colostrum obtained from women vaccinated with pneumococcal vaccine during pregnancy inhibits epithelial adhesion of Streptococcus pneumoniae; Deubzer HE et al.; Prevention of nasopharyngeal colonization may reduce the burden of pneumococcal infection during infancy . Colostrum obtained from Gambian mothers who had been vaccinated with either Pneumovax II or Mengivax A&C (n=8 per group) during pregnancy was examined for inhibition of adherence of Streptococcus pneumoniae serotypes 6B and 14 to pharyngeal epithelial cells in vitro . Pneumococcal adherence was significantly reduced in the presence of breast milk (P< or =.0001 for S . pneumoniae serotype 14; P=.036 for serotype 6B), independent of the concentration of secretory IgA antibodies . Maternal vaccination with polyvalent pneumococcal polysaccharide vaccine boosts the capacity of colostrum to inhibit adherence of pneumococci to pharyngeal epithelial cells . In breast-feeding populations, maternal vaccination might prevent pneumococcal disease in young infants.

Zhonghua Kou Qiang Yi Xue Za Zhi, 2004 Sep, 39(5), 382 - 5
{Preliminary study on gene related to acid tolerance of Streptococcus mutans.}; Wei H et al.; OBJECTIVE: To construct an acid-sensitive mutant of Streptococcus mutans (S . mutans) by transposon mutagenesis and to find a new gene related to the acid tolerance of S . mutans . METHODS: The transposon Tn917 was delivered into S . mutans UA159 by the temperature-sensitive plasmid pTV1-OK bearing Tn917 and transposition of Tn917 was induced after incubation at non-permissive temperature (42 degrees C) . Transposants harboring Tn917 in the chromosome were screened for the selection of mutant that had diminished growth at low pH . Southern analysis was performed with EcoRI (no cut within Tn917) digests of S . mutans UA159 and the selected aid-sensitive mutant, with DIG-labeled probe of 4.3 kb KpnI fragment of pTV1-OK containing Tn917 . Genetic backcross experiment was performed by transforming the genome of the mutant to another S . mutans strain MT8148 to determine the linkage of Tn917 insertion to the change of phenotype (acid-sensitivity) . Comparison of the abilities to grow at low pH, the glycolytic pH drop and killing pH values were done between the acid-sensitive mutant and the parent strain . The asymmetric PCR method was used to obtain the fragment flanking Tn917 and the PCR products were cloned to pMD18-T vector for sequencing . RESULTS: One mutant that showed no growth at pH 5.0 was isolated from 2 316 transposants and was named as b23 . Southern analysis and genetic backcross experiment confirmed the linkage between single Tn917 insertion into the chromosome and the phenotypic change (acid sensitive) . b23 was less acid tolerant than UA159 in that it showed poorer growth at low pH and higher glycolytic pH minimum and higher killing pH . BLAST results indicated that Tn917 inserted into the genome of S . mutans UA159 at the site of 996 123 bp . CONCLUSION: An acid-sensitive mutant of S . mutans was successfully constructed and a new gene that is responsible for the acid tolerance in S . mutans UA159 was revealed.

Clin Exp Immunol, 2004 Nov, 138(2), 290 - 8
Glycolytic enzymes associated with the cell surface of Streptococcus pneumoniae are antigenic in humans and elicit protective immune responses in the mouse; Ling E et al.; Streptococcus pneumoniae is a leading cause of otitis media, sinusitis, pneumonia, bacteraemia and meningitis worldwide . The drawbacks associated with the limited number of various capsular polysaccharides that can be included in the polysaccharide-based vaccines focuses much attention on pneumococcal proteins as vaccine candidates . We extracted an enriched cell wall fraction from S . pneumoniae WU2 . Approximately 150 soluble proteins could be identified by 2D gel electrophoresis . The proteins were screened by 2D-Western blotting using sera that were obtained longitudinally from children attending day-care centres at 18, 30 and 42 months of age and sera from healthy adult volunteers . The proteins were further identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry . Seventeen proteins were antigenic in children and adults, of which 13 showed an increasing antibody response with age in all eight children analysed . Two immunogenic proteins, fructose-bisphosphate aldolase (FBA) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and a control protein with known low immunogenicity, heat shock protein 70 (DnaK), were expressed in Escherichia coli, purified and used to immunize mice . Mouse antibodies elicited to the recombinant (r) FBA and rGAPDH were cross-reactive with several genetically unrelated strains of different serotypes and conferred protection to respiratory challenge with virulent pneumococci . In addition, the FBA used in this study (NP_345117) does not have a human ortholog and warrants further investigation as a candidate for a pneumococcal vaccine . In conclusion, the immunoproteomics based approach utilized in the present study appears to be a suitable tool for identification of novel S . pneumoniae vaccine candidates.

Clin Exp Immunol, 2004 Nov, 138(2), 195 - 201
The role of pneumolysin in pneumococcal pneumonia and meningitis; Hirst RA et al.; Diseases caused by Streptococcus pneumoniae include pneumonia, septicaemia and meningitis . All these are associated with high morbidity and mortality . The pneumococcus can colonize the nasopharynx, and this can be a prelude to bronchopneumonia and invasion of the vasculature space . Proliferation in the blood can result in a breach of the blood-brain barrier and entry into the cerebrospinal fluid (CSF) where the bacteria cause inflammation of the meningeal membranes resulting in meningitis . The infected host may develop septicaemia and/or meningitis secondary to bronchopneumonia . Also septicaemia is a common precursor of meningitis . The mechanisms surrounding the sequence of infection are unknown, but will be dependent on the properties of both the host and bacterium . Treatment of these diseases with antibiotics leads to clearance of the bacteria from the infected tissues, but the bacteriolytic nature of antibiotics leads to an acute release of bacterial toxins and thus after antibiotic therapy the patients can be left with organ-specific deficits . One of the main toxins released from pneumococci is the membrane pore forming toxin pneumolysin . Here we review the extensive studies on the role of pneumolysin in the pathogenesis of pneumococcal diseases.

Autoimmunity, 2004 May, 37(3), 203 - 10
Antigenic complementarity resulting in idiotype-antiidiotype immune complexes: possible contributor to AIDS pathogenesis and autoimmunity; Root-Bernstein R et al.; One hundred and sixty seven combinations of viral + viral antibodies or viral + bacterial antibodies were tested for their ability to precipitate each other . Some antibodies produced against HIV epitopes recognize and precipitate some antibodies produced against cytomegalovirus (CMV), hepatitis B virus (HBV) core antigen, and Mycobacteria tuberculosis (MTb) and Staphylococcus epitopes but not those against HBV surface antigen, herpes simplex types 1 and 2 (HSV1 and HSV2) or Epstein-Barr virus (EBV), Streptococcus, or Escherichia coli . In addition, CMV antibodies precipitate those of HBV core and surface antigens as well as MTb, but not HSV, HSV2, EBV, Streptococcus or E . coli . HBV core (but not surface) antibodies precipitated Mycobacterium avium antibodies (MAv) but not MTb, Streptococcus, Staphylococcus or E . coli antibodies . Binding constants vary between kds of 10(-9) and 10(-7) M . Interactive antibodies act like idiotype-antiidiotype pairs suggesting that the inducing antigens are molecularly complementary . The resulting antibody interactions may explain the formation of circulating immune complexes that are commonly found in AIDS and in other diseases characterized by multiple, concurrent infections . This observation suggests that AIDS pathogenesis may involve autoimmune mechanisms in which the immune system attacks itself to form antibody-antibody circulating immune complexes that contribute to the hypergammaglobulinemia characteristic of AIDS . Complementary cofactor infections in AIDS may therefore contribute to the immunosuppression of the syndrome and difficulties treating these corresponding infections.

J Microbiol Immunol Infect, 2004 Oct, 37(5), 307 - 9
Favorable outcome of infective endocarditis due to Streptococcus agalactiae after conservative treatment; Chen SC et al.; Infective endocarditis due to Streptococcus agalactiae is uncommon and carries an ominous prognosis, leading some authors to advocate early surgery . This report describes an 83-year-old woman with community-acquired infective endocarditis due to S . agalactiae . The patient, who had a history of surgery for colon cancer, presented with fever, agitation and general malaise . She achieved a favorable outcome with antibiotic treatment only . For infective endocarditis due to S . agalactiae, appropriate antimicrobial agents should be started as soon as possible, with surgery reserved for those cases of particular indication.

J Med Microbiol, 2004 Nov, 53(Pt 11), 1109 - 17
Global distribution of Streptococcus pneumoniae serotypes isolated from paediatric patients during 1999-2000 and the in vitro efficacy of telithromycin and comparators; Farrell DJ et al.; Few data exist on the distribution of Streptococcus pneumoniae serotypes in many countries and in non-invasive disease overall . Here, data are presented from 772 paediatric isolates from children with community-acquired respiratory tract infections isolated from the PROTEKT global surveillance study during 1999-2000 . Overall, 60.0 % of isolates were covered by the 7-valent pneumococcal vaccine formulation (PCV7), with greater coverage in the USA compared with Europe (69.6 vs 55.5 %, P = 0.014) . Geographically dispersed clones of serogroups 3, 11 and 15 accounted for most of the isolates outside PCV7 coverage . Overall, macrolide, penicillin and cotrimoxazole non-susceptibility rates were high; however, all isolates were susceptible to telithromycin . Although only 7.4 % of isolates were resistant to amoxycillin/clavulanate, a higher prevalence of resistance was found in isolates from the USA and South Korea . This study shows the feasibility and importance of serotyping antibiotic surveillance study isolates and the potential of telithromycin as an important option for empiric therapy.

J Med Microbiol, 2004 Nov, 53(Pt 11), 1097 - 9
Genetic relatedness of antibiotic-resistant pneumococci isolated during case clusters; Clarke SC et al.; Multilocus sequence typing of Streptococcus pneumoniae associated with two case clusters of disease is reported here for the first time . Isolates from the first cluster were serotype 19F, resistant to penicillin and erythromycin, and were characterized as ST 320 . Isolates from the second cluster were serogroup 4, resistant to ciprofloxacin, and were characterized as ST 206 . Therefore, the isolates from these clusters were antibiotic-resistant, of serotypes infrequently isolated, and of uncommon sequence types.

Emerg Infect Dis, 2004 Aug, 10(8), 1455 - 60
Group G streptococcal bacteremia in Jerusalem; Cohen-Poradosu R et al.; Group G Streptococcus (GGS) can cause severe infections, including bacteremia . These organisms often express a surface protein homologous to the Streptococcus pyogenes M protein . We retrospectively studied the characteristics of patients from the Hadassah Medical Center with GGS bacteremia from 1989 to 2000 . Ninety-four cases of GGS bacteremia were identified in 84 patients . The median age was 62 years, 54% were males, and 92% had underlying diseases (35% had a malignancy, and 35% had diabetes mellitus) . The most frequent source for bacteremia was cellulitis (61%) . emm typing of 56 available isolates disclosed 13 different types, including 2 novel types . Six patients had recurrent bacteremia with two to four bacteremic episodes, five had chronic lymphatic disorders, and two had emm type stG840.0 in every episode . Recurrent bacteremia has not been described for invasive group A Streptococcus . We describe an entity of recurrent GGS bacteremia, which is associated with lymphatic disorders and possibly with emm stG840.0.

Emerg Infect Dis, 2004 Aug, 10(8), 1412 - 9
Serotype III Streptococcus agalactiae from bovine milk and human neonatal infections; Bohnsack JF et al.; Streptococcus agalactiae (group B streptococcus {GBS}) causes invasive human infections and bovine mastitis . This study examined the genetic relationship between bovine and human serotype III GBS by using molecular techniques that classify human serotype III GBS into four distinct phylogenetic lineages . Bovine serotype III GBS were largely contained in two lineages, which are distinct from the two major lineages (restriction digest types III-2 and III-3) that infect human neonates . One of the bovine lineages closely resembles the human III-1 lineage, whose members occasionally cause human neonatal infections . The bovine strains in the other lineage characteristically have an initiation factor IF2 gene (infB) H allele and multilocus sequence types that are not found in human GBS strains . Evidence suggests that this "H allele" lineage is related to the human III-3 lineage . These results support the assertion that human and bovine GBS are largely unrelated and provide further insight into the genetic relation between human and bovine GBS.

Am J Hematol, 2004 Nov, 77(3), 282 - 6
Streptococcus bovis septic shock due to contaminated transfused platelets; Chang AH et al.; Although most physicians and the public are primarily concerned about the risk of transmitting human immunodeficiency virus (HIV) or hepatitis virus during a platelet transfusion, bacterial contamination is actually the most common infectious complication . Unlike red blood cells, platelets are stored at room temperature (20-24 degrees C), which raises the risk of bacterial proliferation . The risk of bacterial sepsis is 2.5-fold higher for each unit of transfused platelets compared to each unit of red blood cells . We report an unusual case of Streptococcus bovis septic shock associated with a contaminated platelet transfusion.

Am J Hematol, 2004 Nov, 77(3), 277 - 81
Pneumococcemia as the presenting feature of multiple myeloma; Costa DB et al.; Multiple myeloma is associated with a susceptibility to bacterial infections, specifically for encapsulated organisms such as Streptococcus pneumoniae . However, severe bacterial infection as the initial presentation of this disease has been rarely reported . The most common presenting features are anemia, lytic lesions, hypercalcemia, and renal failure . We report two cases of pneumococcal bacteremia as the initial manifestation of an underlying multiple myeloma . The first case is of a 68-year-old woman with pneumococcal pneumonia and bacteremia, presenting with a white blood cell count of 900/microL and mild anemia . Further work-up disclosed monoclonal IgG kappa and 50% plasma cells in bone marrow . Her course was complicated by acute renal failure requiring hemodialysis . The second patient is a 57-year-old man presenting with acute pneumococcal meningitis and bacteremia . Due to prior bacterial epiglottitis, further work-up disclosed IgG lambda monoclonal spike and 40% plasma cells in bone marrow . Both cases responded to antibiotic therapy without complications . These two cases add to the few patients described in the literature with pneumococcemia as the first sign of multiple myeloma . Features that were common in most of these cases, and that should lead to a suspicion of myeloma in an otherwise asymptomatic patient, are S . pneumoniae bacteremia, leukopenia, mild anemia, history of prior bacterial infections, and indirect evidence of a paraproteinemia, such as increased total protein levels with low albumin.

Cochrane Database Syst Rev . 2004 Oct 18;(4):CD004977.
Pneumococcal conjugate vaccines for preventing vaccine-type invasive pneumococcal disease and pneumonia with consolidation on x-ray in children under two years of age; Lucero M et al.; BACKGROUND: Pneumonia, most commonly caused by Streptococcus pneumoniae (Pnc), is a major cause of morbidity and mortality among young children especially in developing countries . Recently, the prevalence of antibiotic-resistant Pnc has increased worldwide such that the effectiveness of preventive strategies, like the new pneumococcal conjugate vaccines (PCV) on rates of invasive pneumococcal disease (IPD) and pneumonia, needs to be evaluated . OBJECTIVES: To determine the efficacy of PCV in reducing the incidence of IPD due to vaccine serotypes (VT) and x-ray confirmed pneumonia with consolidation of unspecified etiology in children who received PCV before 12 months of age . SEARCH STRATEGY: We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1 2004), MEDLINE (1990 to March 2004) and EMBASE (1990 to December 2003) . Reference list of articles, and books of abstracts of relevant symposia, were hand searched . Researchers in the field were also contacted . SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing PCV with placebo, or another vaccine, among children below two years with IPD and clinical/radiographic pneumonia as outcomes . DATA COLLECTION AND ANALYSIS: Two reviewers independently identified eligible studies, assessed trial quality, and extracted data . Differences were resolved by discussion . The inverse variance method was used to pool effect sizes . MAIN RESULTS: We identified four trials assessing the efficacy of PCV in reducing the incidence of IPD, two on x-ray confirmed pneumonia as outcome, and one on clinical pneumonia, with or without x-ray confirmation . Results from pooling HIV-1 negative children from the South African study with the other studies were as follows: the pooled vaccine efficacy (VE) for vaccine-type IPD was 88% (95% confidence interval (CI) 73% to 94%; fixed effect and random effects models), the effect measure was statistically significant (p <0.00001) and there was no heterogeneity (p = 0.77I(2) 0%); the pooled VE for all-serotype IPD was 66% (95% CI 46% to 79%; fixed effect model), the effect measure was statistically significant (p <0.00001) and there was no statistical heterogeneity (p = 0.09, I(2) 51%); the pooled VE for x-ray confirmed pneumonia was 22% (95% CI 11% to 31%; both fixed effect and random effects models) and there was no statistical heterogeneity (p = 0.80, I(2) 0%) . Analyses that included all the children in the South African study (HIV-1 negative and HIV-1 positive children) and pooled with data from the other studies gave very similar results . REVIEWERS' CONCLUSIONS: PCV is effective in reducing the incidence of IPD from all serotypes but exerts a greater effect in reducing VT IPD . Although PCV is also effective in reducing the incidence of x-ray confirmed pneumonia, there are still uncertainties about the definition of this outcome . Additional randomised controlled trials are currently in progress.

Drugs Aging, 2004, 21(13), 851 - 64
Drug treatment of pneumococcal pneumonia in the elderly; Neralla S et al.; Streptococcus pneumoniae has been recognised as a major cause of pneumonia since the time of Sir William Osler . Drug-resistant S . pneumoniae (DRSP), which have gradually become resistant to penicillins as well as more recently developed macrolides and fluoroquinolones, have emerged as a consequence of indiscriminate use of antibacterials coupled with the ability of the pneumococcus to adapt to a changing antibacterial milieu . Pneumococci use cell wall choline components to bind platelet-activating factor receptors, colonise mucosal surfaces and evade innate immune defenses . Numerous virulence factors that include hyaluronidase, neuraminidase, iron-binding proteins, pneumolysin and autolysin then facilitate cytolysis of host cells and allow tissue invasion and bloodstream dissemination . Changes in pneumococcal cell wall penicillin-binding proteins account for resistance to penicillins, mutations in the ermB gene cause high-level macrolide resistance and mutations in topoisomerase IV genes coupled with GyrA gene mutations alter DNA gyrase and lead to high-level fluoroquinolone resistance . Risk factors for lower respiratory tract infections in the elderly include age-associated changes in oral clearance, mucociliary clearance and immune function . Other risks for developing pneumonia include poor nutrition, hypoalbuminaemia, bedridden status, aspiration, recent viral infection, the presence of chronic organ dysfunction syndromes including parenchymal lung disease and recent antibacterial therapy . Although the incidence of infections caused by DRSP is rising, the effect of an increase in the prevalence of resistant pneumococci on mortality is not clear . When respiratory infections occur, rapid diagnosis and prompt, empirical administration of appropriate antibacterial therapy that ensures adequate coverage of DRSP is likely to increase the probability of a successful outcome when treating community-acquired pneumonia in elderly patients, particularly those with multiple risk factors for DRSP . A chest x-ray is recommended for all patients, but other testing such as obtaining a sputum Gram's smear is not necessary and should not prolong the time gap between clinical suspicion of pneumonia and antibacterial administration . The selection of antibacterials should be based upon local resistance patterns of suspected organisms and the bactericidal efficacy of the chosen drugs . If time-dependent agents are chosen and DRSP are possible pathogens, dosing should keep drug concentrations above the minimal inhibitory concentration that is effective for DRSP . Treatment guidelines and recent studies suggest that combination therapy with a beta-lactam and macrolide may be associated with a better outcome in hospitalised patients, and overuse of fluoroquinolones as a single agent may promote quinolone resistance . The ketolides represent a new class of macrolide-like antibacterials that are highly effective in vitro against macrolide- and azalide-resistant pneumococci . Pneumococcal vaccination with the currently available polysaccharide vaccine is thought to confer some preventive benefit (preventing invasive pneumococcal disease), but more effective vaccines, such as nonconjugate protein vaccines, need to be developed that provide broad protection against pneumococcal infection.

Int J Med Microbiol, 2004 Sep, 294(2-3), 157 - 68
Mosaic genes and mosaic chromosomes-genomic variation in Streptococcus pneumoniae; Bruckner R et al.; The genome sequences of two strains of Streptococcus pneumoniae, one of the major human pathogens, are currently available: that of the nonencapsulated laboratory strain R6, the origin of which dates back to the early 20th century, and of the serotype 4 TIGR strain isolated recently . The two genomes are not only different in size (2 versus 2.16 Mb) but differ also by approximately 10% of their genes, many of which being organized in large clusters . Their strain-specific genes and gene clusters are described here . The R6 genome contains 69 kb organized in six large regions that are absent from the TIGR strain, which in turn contains an extra 157kb in twelve clusters compared to R6 . In addition, the TIGR strain contains 13 clusters of 4 kb and larger that are not shared by a variety of genetically different S . pneumoniae strains . Many regions bear signs of gene transfer events such as the presence of insertion sequences, transposable elements, and putative site-specific integrases/recombinases . Three strain-specific regions are devoted to genes encoding proteins with the cell wall anchor motif LPXTG which are important for the interaction with host cells and appear to be highly variable, similar to cell wall-associated choline-binding proteins.

Lasers Surg Med, 2004, 35(4), 263 - 8
Microbial reduction in periodontal pockets under exposition of a medium power diode laser: an experimental study in rats; Fontana CR et al.; BACKGROUND AND OBJECTIVE: This work evaluates the application of a 810 nm diode laser operating in the range of 400-1,200 mW for bacterial reduction at periodontal treatment . The aim of this study is to examine the immediate effect of the diode medium power laser in reducing the bacterial concentration at periodontal pockets induced in Wistar rats . STUDY DESIGN/MATERIALS AND METHODS: Two bacterial collections were performed on each animal . Microbiological samples were collected before and immediately after laser irradiation . In each group of laser power, eight animals were used, totaling 40 animals . RESULTS: The initial and the final bacterial count revealed that laser irradiation induces considerable bacterial elimination, especially for Prevotella sp, Streptococcus beta-hemolitico, Fusobacterium sp, Pseudomonas sp . CONCLUSIONS: Our results indicate that this laser can constitute an alternative device to traditional infrared systems for bacterial reduction, with some advantage when economical and practical standpoints are considered . (c) 2004 Wiley-Liss, Inc.

Int Microbiol, 2004 Sep, 7(3), 163 - 71
Streptococcus pneumoniae and its bacteriophages: one long argument; Lopez R; Infectious diseases currently kill more than 15 million people annually, and the WHO estimates that every year 1.6 million people die from pneumococcal diseases . Streptococcus pneumoniae (pneumococcus), a bacterium with a long biological pedigree, best illustrates the rapid evolution of antibiotic resistance, which has led to major public health concern . This article discusses the molecular basis of the two main virulence factors of pneumococcus, the capsule and cell-wall hydrolases, as well as new approaches to developing medicinal weapons for preventing pneumococcal infections . In addition, current knowledge regarding pneumococcal phages as potential contributors to virulence and the use of lytic enzymes encoded by these phages as therapeutic tools is reviewed.

Oral Microbiol Immunol, 2004 Dec, 19(6), 408 - 10
Transmission of Streptococcus mutans in a group of Turkish families; Ersin NK et al.; BACKGROUND/AIMS: To investigate the transmission of Streptococcus mutans in a group of Turkish families using AP-polymerase chain reaction (PCR) detection . METHODS: Eight mothers who had high S . mutans levels in unstimulated saliva and 8 children aged between 2 and 3 years participated in the study . Plaque samples from each child were collected with the tips of sterile toothpicks for S . mutans counts . Although not part of the original study design, S . mutans samples were also obtained from the unstimulated saliva of the three fathers who shared the same households . Three typical isolates of S . mutans were isolated from TYCSB agar of each subject and identified by sugar fermentation tests . S . mutans ATCC 10449 was used as the reference strain . AP-PCR was conducted with OPA-05 primer . RESULTS: All of the mothers and fathers shared the similar genotypes within their children . The fathers also harbored similar genotypes to their spouses . CONCLUSION: The mothers or the fathers could be the source for the transmission of S . mutans to their children.

Oral Microbiol Immunol, 2004 Dec, 19(6), 386 - 9
Molecular analysis of age-related changes of Streptococcus anginosus group and Streptococcus mitis in saliva; Morita E et al.; The purpose of this study was to survey the prevalence of streptococcal species, especially Streptococcus anginosus (which has been reported to be associated with cancer in the upper digestive tract), Streptococcus constellatus, and Streptococcus intermedius in the saliva of different age groups . A sequence analysis of 16S rDNA was performed and DNA quantified using real-time polymerase chain reaction . The S . anginosus level increased with age, whereas the levels of S . constellatus and S . intermedius did not change . Streptococcus mitis was the predominant species in the saliva of all the age groups but, unlike the S . anginosus, the proportion of S . mitis in the salivary bacteria decreased with age . The increase in S . anginosus with age should be carefully monitored because of its association with diseases, including cancer.

Mol Microbiol, 2004 Nov, 54(3), 783 - 94
Release of DNA into the medium by competent Streptococcus pneumoniae: kinetics, mechanism and stability of the liberated DNA; Moscoso M et al.; The release of chromosomal DNA into culture media has been reported for several naturally transformable bacterial species, but a direct link between competence development and the liberation of DNA is generally lacking . Based on the analysis of strains with mutations in competence-regulatory genes and the use of conditions favouring or preventing competence, we provide evidence that DNA release is triggered by the induction of competence in Streptococcus pneumoniae . Kinetic analyses revealed that whereas competence was maximal 20 min after addition of competence-stimulating peptide, and then decreased, the amount of liberated DNA continued to increase and reached a maximum in stationary phase, when cells are no longer competent for DNA uptake . These data are not consistent with the proposal that release of DNA by a fraction of the population is coordinated with uptake by the remainder . Moreover, we observed that an unidentified DNase was specifically induced or released in competent cultures, and that together with the major pneumococcal endonuclease, EndA, it could degrade released DNA . Nearby complete abolition of release in a mutant lacking both the major autolysin, LytA, and the autolytic lysozyme, LytC, indicated that DNA liberation occurs by LytA-LytC-dependent cell lysis . These observations suggest that competence-dependent DNA release is one facet of a more general phenomenon of sensitization to autolysis that reaches its maximum in stationary phase.

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