J Perinatol, 2003 Jun, 23(4), 265 - 71 Neonatal early-onset group B streptococcal disease in the era of intrapartum chemoprophylaxis: residual problems; Pinto NM et al.; OBJECTIVE: To identify limitations of current strategies for intrapartum prophylaxis of neonatal early-onset group B streptococcal infection . METHODS: Retrospective review of infants with culture-proven early-onset group B streptococcal infection admitted to two nurseries and their mothers from July 1992, when ACOG and AAP guidelines for intrapartum prophylaxis were first issued, through December 2001 . Information was recorded regarding clinical risk factors for early-onset group B streptococcal infection, collection and processing of specimens to assess maternal colonization, delivery of prophylaxis, duration of hospitalization before delivery, and outcome . RESULTS: Among 92 infants with early-onset group B streptococcal infection admitted from 23 institutions, 68 had received no intrapartum prophylaxis . Of these 68 who received no prophylaxis, 34 had identifiable risk factors before delivery (32 clinical, two positive maternal culture), while 34 had no risk factors . Prenatal culture for group B streptococcal colonization was performed in 22 of these women . Of the 18 cultures that were negative for group B streptococcus, 15 were obtained using suboptimal culture technique or were collected more than 6 weeks before delivery . Of the 68 with no prophylaxis, 14 required extracorporeal membrane oxygenation and three died . Of the 24 who received some intrapartum prophylaxis, nine had received >/=two doses for >/=4 hours immediately before delivery . Among the 24 receiving some intrapartum prophylaxis, two required extracorporeal membrane oxygenation and one died . No deaths occurred in those who received >4 hours of prophylaxis, although one such infant required extracorporeal membrane oxygenation . After the CDC guidelines were issued in May 1996, there was a decrease both in the number of cases of early-onset group B streptococcal infection (56 versus 36) as well as in the number with clinical risk factors but no intrapartum prophylaxis (24/56 (43%) versus 5/28 (18%)) . CONCLUSIONS: The use of clinical risk factors alone will inevitably result in missed opportunity for intrapartum antibiotic prophylaxis . With maternal screening, false-negative results will be reduced but not necessarily eliminated by assuring that specimens are obtained from proper sites using selective media within 6 weeks of delivery . Better strategies are needed to assure timely administration when prophylaxis is indicated . The nine neonates with early-onset group B streptococcal infection despite intrapartum antibiotics for the recommended duration illustrate that disease may occur even when guidelines are implemented appropriately. Biochem Soc Trans, 2003 Jun, 31(Pt 3), 716 - 8 Immunoglobulin-binding domains: Protein L from Peptostreptococcus magnus; Housden NG et al.; Protein L is a multidomain cell-wall protein isolated from Peptostreptococcus magnus . It belongs to a group of proteins that contain repeated domains that are able to bind to Igs without stimulating an immune response, the most characterized of this group being Protein A ( Staphylococcus aureus ) and Protein G ( Streptococcus ) . Both of these proteins bind predominantly to the interface of C(H)2-C(H)3 heavy chains, while Protein L binds exclusively to the V(L) domain of the kappa -chain . The function of these proteins in vivo is not clear but it is thought that they enable the bacteria to evade the host's immune system . Two binding sites for kappa -chain on a single Ig-binding domain from Protein L have recently been reported and we give evidence that one site has a 25-55-fold higher affinity for kappa -chain than the second site. J Med Chem, 2003 Jun 5, 46(12), 2304 - 12 Novel dihydrofolate reductase inhibitors . Structure-based versus diversity-based library design and high-throughput synthesis and screening; Wyss PC et al.; Novel 2,4-diaminopyrimidines bearing N,N-disubstituted aminomethyl residues at the 5-position were designed as dihydrofolate reductase (DHFR) inhibitors . These compounds were obtained by treatment of 1-{(2,4-diamino-5-pyrimidinyl)methyl}pyridinium bromide with secondary amines in a polar solvent and in the presence of triethylamine at room temperature . The procedure was found to be very efficient and suitable for application in high-throughput synthesis . In addition, we found that high-throughput screening for enzymatic and in vitro antibacterial activity could be performed on crude reaction mixtures, thus avoiding any purification step . Over 1200 proprietary secondary amines were selected for high-throughput synthesis, based on structural and diversity-related criteria, and the resulting products were submitted to high-throughput screening . A greater number of hits, and significantly more active compounds, were obtained through structure-based library design than through diversity-based library design . Different classes of inhibitors of DHFR were identified in this way, including compounds derived from di-, tri-, and tetracyclic amines . In general, these products showed high activity against the enzymes derived from both TMP-sensitive and TMP-resistant Streptococcus pneumoniae . Some compounds possessed appreciable selectivity for the bacterial over the human enzyme, whereas other compounds were not at all selective . In most cases, active enzyme inhibitors also displayed antibacterial activity. FEMS Immunol Med Microbiol, 2003 Jun 10, 37(1), 53 - 7 Protective efficacy of PspA (pneumococcal surface protein A)-based DNA vaccines: contribution of both humoral and cellular immune responses; Miyaji EN et al.; Streptococcus pneumoniae is a major public health problem and new strategies for the development of cost-effective alternative vaccines are important . The use of protein antigens such as PspA (pneumococcal surface protein A) is a promising approach to increase coverage at reduced costs . We have previously described the induction of a strong antibody response by a DNA vaccine expressing a C-terminal fragment of PspA . Fusion of this fragment with the cytoplasmic variant of SV40 large T-antigen (CT-Ag) caused reduction in specific interferon-gamma produced by stimulated spleen cells . In this work we show that the DNA vaccine expressing the C-terminal region of PspA elicits significant protection in mice against intraperitoneal challenge with a virulent strain of S . pneumoniae . Furthermore, fusion with CT-Ag completely abrogated the protection elicited by DNA immunization with this fragment . In this case, protection did not correlate with total anti-PspA antibody production nor with total IgG2a levels . The anti-PspA sera obtained from both constructs showed equivalent opsonic activity of pneumococci, indicating that the antibodies produced were functional . We could, though, observe a correlation between a lower IgG1:IgG2a ratio, which is indicative of a stronger bias towards Th1 responses, and protection . We also show that a vector expressing the most variable N-terminal alpha-helical region induces higher antibody formation, with increased protection of mice against intraperitoneal challenge with a more virulent strain of S . pneumoniae . As a whole, these results indicate that antibodies elicited against PspA would not be solely responsible for the protection induced by DNA vaccination and that cell-mediated immune responses could also be involved in protection against pneumococcal sepsis. FEMS Microbiol Lett, 2003 May 28, 222(2), 263 - 71 Novel protein vaccine candidates against Group B streptococcal infection identified using alkaline phosphatase fusions; Hughes MJ et al.; Using an alkaline phosphatase-based genetic screening method, we identified a number of proteins that are potentially located on the outer surface of Group B streptococcus (Streptococcus agalactiae) . In an enzyme-linked immunosorbent assay, antisera raised against two of the proteins, the streptococcal yutD homologue and a subunit of an ABC transporter, recognised clinically important serotypes of Group B streptococcus . In a neonatal rat model, purified IgG from the sera conferred significant levels of protection against a lethal challenge infection . The proteins identified show potential as protein subunit candidates for vaccines against Group B streptococcal disease in neonates. FEMS Microbiol Lett, 2003 May 28, 222(2), 193 - 7 Molecular and biochemical analysis of the system regulating the lytic/lysogenic cycle in the pneumococcal temperate phage MM1; Obregon V et al.; The temperate phage MM1 forms stable lysogens in Streptococcus pneumoniae . We report here the first characterization of the lysogenic control region in Pneumococcus which contains two functional divergent promoters (P(R) and P(L)) . MM1 encodes a 14-kDa cI protein (CI) that appears to be responsible for maintaining the lysogenic state in Pneumococcus since it prevents elongation of the transcripts controlled by P(R) and P(L). BMC Gastroenterol . 2003 May 24;3(1):9. Spectrum and antibiotic sensitivity of bacteria contaminating the upper gut in patients with malabsorption syndrome from the tropics; Ghoshal U et al.; BACKGROUND: Various causes of malabsorption syndrome (MAS) are associated with intestinal stasis that may cause small intestinal bacterial overgrowth (SIBO) . Frequency, nature and antibiotic sensitivity of SIBO in patients with MAS are not well understood . METHODS: Jejunal aspirates of 50 consecutive patients with MAS were cultured for bacteria and colony counts and antibiotic sensitivity were performed . Twelve patients with irritable bowel syndrome were studied as controls . RESULTS: Culture revealed growth of bacteria in 34/50 (68%) patients with MAS and 3/12 controls (p < 0.05) . Colony counts ranged from 3 x 10(2) to 10(15) (median 10(5)) in MAS and 100 to 1000 (median 700) CFU/ml in controls (p 0.003) . 21/50 (42%) patients had counts GreaterEqual;105 CFU/ml in MAS and none of controls (p < 0.05) . Aerobes were isolated in 34/34 and anaerobe in 1/34 . Commonest Gram positive and negative bacteria were Streptococcus species and Escherichia coli respectively . The isolated bacteria were more often sensitive to quinolones than to tetracycline (ciprofloxacin: 39/47 and norfloxacin: 34/47 vs . tetracycline 19/47, <0.01), ampicillin, erythromycin and co-trimoxazole (21/44, 14/22 and 24/47 respectively vs . tetracycline, p = ns) . CONCLUSIONS: SIBO is common in patients with MAS due to various causes and quinolones may be the preferred treatment . This needs to be proved further by a randomized controlled trial. An Med Interna, 2003 Apr, 20(4), 179 - 82 {Utility of anaerobic blood cultures in extra-hospitalary bacteremias}; Ruiz-Giardin JM et al.; OBJECTIVE: To compare the rentability of anaerobic hemocultures with aerobic cultures in patients suffering bacteremia, trying to analyze the rentability of anaerobic cultures . METHODS: There were analyzed all the hemocultures taken by medical decision for one month . There were taken three extractions by patient in different venopunctures points . In each extraction was taken 10 ml (5 ml in aerobic bottle, and 5 ml in anaerobic bottle) . There were compared microorganism isolated in aerobic bottles and anaerobic bottles . Three physician analyzed all the clinical dates of the patients with positive hemocultures and classified them as negatives, contaminants and significant . RESULTS: There were taken hemocultures of 180 patients . There were analyzed 152 hemocultures groups (3 extractions aerobic-anaerobic), without studying 28 owe to not following the study protocol 24 (13.3%) or because of not possibility of studying clinical story 4 (2.2%) . Aerobic extractions: Negatives 91 (59.86%), contaminants 36 (23.68%), significant with or without contaminant 25 (16.44%) . Anaerobic extractions: Negatives 127 (83.5%), contaminants 2 (1.31%); significant with or without contaminant 23 (15.13%) . There are 6 (8.6%) significant positive isolated in anaerobic bottles, that were negative in aerobic bottles, and are: 3 E . coli, 1 K . pneumoniae, 1 Peptostreptococcus sp, 1 Bacteroides sp, and over the total significant isolated (31) are the 19.35% . Both anaerobic bacteremias were clinically suspected . Contaminant microorganism more frequently isolated in aerobic bottles was Staphylococcus sp, 25 cases (69.44% of all contaminants) . Significant microorganism more frequently isolated was E . coli (in anaerobic bottles too) in 12 cases (38.70%) of all significant isolated, following by Streptococcus pneumoniae with 4 cases (12.9%) . CONCLUSIONS: We recommend collection of one aerobic and one anaerobic blood culture bottle per blood culture set because the global rentability of hemocultures is increased significantly. Zhonghua Er Bi Yan Hou Ke Za Zhi, 2002 Feb, 37(1), 23 - 6 {A comparative experimental study between recombinant active gene 1-deficient mice and C57BL/6 mice model of acute bacterial rhinosinusitis}; Xie M; OBJECTIVE: To explore the infective course of acute bacterial rhinosinusitis in recombinent active gene 1 (Rag 1)-defecient mice (Rag1) and C57BL/6 mice (C57) and the difference between them after intranasal streptococcus pneumoniae inoculation . METHODS: Ten mice of each strain (Rag1 and C57) received Streptococcus pneumoniae strain T59, ATCC 49,619 suspended in trypticase soy broth, and controls (two mice for each strain) received trypticase soy broth alone . After 2, 5, 10 and 14 days, nasal lavage cultures were obtained and then the mice were killed . The heads were embedded with paraffin and serial sections were made for histological analysis . The percentage of sinus cavity occupied by neutrophil cluster (% cluster) and the number of polymorphonuclear leukocytes per square millimeter of sinus mucosa (PMN/mm2) were calculated by the use of a computer-aided microscope in conjunction with a reconstruction and image analysis system . RESULTS: % Cluster and PMN/mm2 in infected mice both of Rag1 and C57 appeared to peak on five and ten days separately, which were significantly heavier than those in controls(P < 0.05) . The infection in C57 decreased by two weeks . But in contrast to C57, the infection in Rag1 had not been controlled and Streptococcus pneumoniae were still seen in the nasal lavage culture by two weeks . This difference between infected Rag1 and infected C57 was significant at P < 0.05 . CONCLUSION: Acute bacterial rhinosinusitis in Rag1 and C57 mice were successfully induced by intranasal inoculation of streptococcus pneunoniae . This bacterial infection in C57 could be controlled completely and rapidly . In contrast, Rag1 failed to control rhinosinusitis and had a tendency to chronic inflammation, suggesting that T- and B-cell-dependent immunity was important for clearance of bacteria from rhinosinus and gene knockout mice was a convenient tool for investigation of the pathogenesis of experimental rhinosinusitis. Zhonghua Er Bi Yan Hou Ke Za Zhi, 2000 Apr, 35(2), 113 - 6 {A novel method for screening anti-inner ear autoantibody in patients with autoimmune diseases}; Zou J et al.; OBJECTIVE: To appraise the clinical value of a newly established method, rapid electric field immobilizing liquid phase molecule dot blot analysis (REILMD), for screening anti-inner ear autoantibody in patients with autoimmune diseases . METHODS: Seventy-one patients with 11 kinds of autoimmune diseases were chosen for the study . Both the general immunity and autoantibodies were tested . In the processes of detection of anti-inner ear autoantibody, REILMD was used for screening, and then the Western blot was used to define the molecular weight of inner ear antigen recognized by the positive autoantibody . RESULTS: Acceleration of erythrocyte sedimentation rate (ES), positive rheumatoid factor (RF), increases in C reactive protein (CRP), IgG and circulating immune complex (CIC) were found in most cases with rheumatoid arthritis (RA) and systemic lupus erythematodes (SLE) . Some of these patients had increased IgA, IgM and C4 . Two of 16 RA had anti-double-stranded DNA (dsDNA) and anti-mitochondria and 4/16 had anti-nucleus antibodies . Eleven of 16 SLE had antinucleus, 7/13 had anti-ribonucleoprotein (RNP), anti-Sjogren syndrome A (SSA) and anti-dsDNA, 3/13 had anti-smooth muscle (Sm) and 1/13 had anti-DNA topoisomerase I (Scl)-70, striated muscle and stomach acid cell antibodies . No autoantibody was detected in AS . Anti-inner ear autoantibody existed in 9 out of 71 patients (13%) with autoimmune diseases, in 2 of 21 patients (10%) with sudden deafness and only in 1 of 48 control subjects (2%, coronary heart disease) . The anti-inner ear autoantibody was positive in 5 of 16 (31%) patients with SLE and 1 each in RA, AS, Behset's disease and streptococcus infection syndrome . In patients with positive anti-inner ear antibody, 67% had anti-nucleus antibody, 50% had anti-RNP and dsDNA antibody . The molecules recognized by the positive anti-inner ear antibody were defined as 52,000, 36,000, 31,000 and 15,000 molecules of inner ear antigen . CONCLUSION: REILMD is a feasible and easy method for screening anti-inner ear autoantibody . Several autoimmune diseases, particularly SLE, may be implicated in damage to the inner ear. J Chromatogr B Analyt Technol Biomed Life Sci, 2003 Jun 25, 790(1-2), 365 - 72 Preparative purification of soybean agglutinin by affinity chromatography and its immobilization for polysaccharide isolation; Franco-Fraguas L et al.; Optimized procedures for the affinity purification of soybean agglutinin (SBA) from soybean flour, and its further immobilization, were developed . Lectin purification on galactosyl-Sepharose yielded 44.5+/-3.5 mg of pure SBA/50 g of flour . To prepare SBA adsorbents, the lectin was immobilized onto 1-cyano-4-(dimethylamino)pyridinium tetrafluoroborate (CDAP) activated Sepharose with high yields (77%) . Feasibility of the use of this improved SBA adsorbent for affinity purification of Streptococcus pneumoniae capsular polysaccharides from strain 14 (CPS-14) at laboratory scale was demonstrated . Using SBA-Sepharose adsorbent (7.0 mg lectin per ml), amounts of 6.3 mg of pure CPS-14 per cycle were produced, the adsorbent being reused up to four times without loss of capacity. Paediatr Drugs, 2003, 5(6), 419 - 29; discussion 430-1 Linezolid: in infants and children with severe Gram-positive infections; Lyseng-Williamson KA et al.; Linezolid is an oxazolidinone antibacterial agent that has inhibitory activity against a broad range of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae . The systemic clearance and, therefore, the area under the plasma concentration-time curve and elimination half-life of linezolid change with increasing age in pediatric patients . With the exception of pre-term neonates aged <1 week, systemic clearance is more rapid in pediatric patients aged 0-11 years than in adolescents . The pharmacokinetic profile of linezolid is similar in adolescents and adults . Linezolid was as effective as vancomycin in the treatment of pediatric patients with Gram-positive infections (clinical cure rate 89.3% vs 84.5%), and as effective as cefadroxil in the treatment of children and adolescents with Gram-positive uncomplicated skin and skin structure infections (91.0% vs 90.0%) in the clinically evaluable population of two randomized, comparator-controlled trials . The clinical cure rate with linezolid was 92.4% in a noncomparative trial in hospitalized pediatric patients with community-acquired pneumonia . All patients with proven pneumococcal pneumonia were considered cured . Linezolid is generally well tolerated . The most common drug-related adverse events in the comparator-controlled trials were diarrhea, nausea, and headache; most events were mild to moderate in severity. Eur Respir J, 2003 May, 21(5), 779 - 84 Chlamydia species as a cause of community-acquired pneumonia in Canada; Marrie TJ et al.; Chlamydia pneumoniae has been implicated as a cause of community-acquired pneumonia (CAP) in several studies . However, there has been no comprehensive study of the role of Chlamydia species (C . pneumoniae, C . psittaci (avian and feline strains) and C . pecorum) as a cause of CAP . The aim of the present study was to determine the role of C . pneumoniae, C . psittaci and C . pecorum as causes of CAP . A prospective cohort observational study of CAP was conducted at 15 teaching centres in eight Canadian provinces between January 1996-October 1997 . Acute (n=539) and convalescent (n=272) serum samples were obtained for determination of antibody titres to C . pneumoniae, C . psittaci, C . pecorum, C . trachomatis, Mycoplasma pneumoniae, Legionella pneumophila serogroups I-VI, Streptococcus pneumoniae and various respiratory viruses . Twelve of 539 (2.2%) patients had acute C . pneumoniae pneumonia and an additional 32 (5.9%) had possible acute infection . C . pneumoniae was the sole pathogen in 16 of 42 (38.1%) of these patients . The most common copathogens were S . pneumoniae, respiratory syncytial virus and influenza virus type A . C . pneumoniae pneumonia patients were older and more likely to show congestive heart failure compared to bacteraemic S . pneumoniae patients . The latter had a lower mean diastolic blood pressure, a higher white blood cell count and a lower arterial carbon dioxide tension . Two patients had antibody titres suggestive of recent infection with the feline strain of C . psittaci . Although numerically Chlamydia pneumoniae is an important cause of community-acquired pneumonia, no distinctive clinical features associated with this pathogen were detected in the present study . Feline Chlamydia psittaci may cause a few cases of community-acquired pneumonia . Avian Chlamydia psittaci should be considered only if there is a compatible epidemiological history. Prog Urol, 2003 Apr, 13(2), 306 - 7 {Pre-pubic abscess of unknown cause}; Peyromaure M et al.; The authors report a case of prepubic abscess in a young man presenting with pain . Surgical exploration revealed a group A Streptococcus abscess . The cause of this abscess was not determined. Brain Res, 2003 Jun 27, 976(2), 139 - 48 Impaired cortical energy metabolism but not major antioxidant defenses in experimental bacterial meningitis; Ghielmetti M et al.; The loss of soluble brain antioxidants and protective effects of radical scavengers implicate reactive oxygen species in cortical neuronal injury caused by bacterial meningitis . However, the lack of significant oxidative damage in cortex {J . Neuropathol . Exp . Neurol . 61 (2002) 605-613} suggests that cortical neuronal injury may not be due to excessive parenchymal oxidant production . To see whether this tissue region exhibits a prooxidant state in bacterial meningitis, we examined the state of the major cortical antioxidant defenses in infant rats infected with Streptococcus pneumoniae . Adenine nucleotides were co-determined to assess possible changes in energy metabolism . Arguing against heightened parenchymal oxidant production, the high NADPH/NADP(+) ratio ( approximately 3:1) and activities of the major antioxidant defense and pentose phosphate pathway enzymes remained unchanged at the time of fulminant meningitis . In contrast, cortical ATP, ADP and total adenine nucleotides were on average decreased by approximately 25% . However, energy depletion did not lead to a significant decrease in adenylate energy charge (AEC) . ATP depletion was likely a consequence of metabolic degradation, since it correlated with both the loss of total adenine nucleotides and accumulation of purine degradation products . Furthermore, the loss of ATP and decrease in AEC correlated significantly with the extent of neuronal injury . These results strongly suggest that energy depletion rather than parenchymal oxidative damage is involved in the observed cortical neuronal injury. Med Arh, 2002, 56(3 Suppl 1), 51 - 3 {Incidence of early-onset neonatal sepsis caused by group B Streptococcus at the Pediatric Clinic of the University Clinical Center in Sarajevo}; Maksic H et al.; Group B Streptococcus (GBS) is the main ethiological agent of neonatal sepsis in the developed countries . Because of high mortality rate American College of Obstetrics and Gynaecologists and Centers for Disease Control published recommendation for prevention of neonatal GBS infection . Program recommends screening of all pregnant women for anogenital GBS infection including intrapartum treatment of pregnant women at high risk, with penicillin or ampicillin . Clindamicin or erythromicin may be used for women allergic to penicillin . Since there is no detailed informations of early-onset neonatal GBS infection in our country, we investigated its incidence in Pediatric Clinic in Sarajevo, from December 1999 (when first case of early-onset GBS infection in last decade was diagnosed) to August 2002 . During that period 7 neonates with early-onset GBS infection were identified (incidence 0.52 per 1000 livebirths) . Four of seven sick newborns died, 2/7 survived with severe neurological sequelae and only one female newborn survived without deficits . In the same period we registered 36 (2.4%) GBS colonised neonates out of 1530 admitted neonates . The number probably is higher because of discharge GBS colonized asymptomatic neonates from Maternity as a healthy to home . Results of this study intend the necessity of implementation guidelines for GBS prevention since early onset GBS infection is becoming as an increasing problems in our population. Genes Immun, 2003 Jun, 4(4), 283 - 8 Polymorphisms in lymphotoxin alpha and CD14 genes influence TNFalpha production induced by Gram-positive and Gram-negative bacteria; Temple SE et al.; Improved understanding of how host genetic variation affects resistance to microbial pathogens could lead to better treatment and/or prevention of infectious diseases . The lymphotoxin alpha (LTA)+250 and CD14-159 polymorphisms are associated with differences in susceptibility or outcome to several infections . We stimulated peripheral blood mononuclear cells (PBMC) from 22 healthy individuals with purified lipopolysaccharide (LPS), heat-killed Escherichia coli or Streptococcus pneumoniae . TNF alpha intracellular protein levels were measured by flow cytometry and mRNA was quantitated by RT-PCR . TNF alpha mRNA levels were higher in LTA+250GG subjects after 4 h incubation with LPS compared with LTA+250AA (T test, P=0.001) . In contrast, after 8 h incubation with S . pneumoniae, there was slightly more TNF alpha mRNA in cells from LTA+250AA subjects . After 4 h incubation with LPS or E . coli, CD14-159TT subjects had higher TNF alpha mRNA levels than CD14-159CC (P=0.05, 0.033, respectively) . Neither polymorphism affected the proportion of cells expressing intracellular TNF alpha protein . This suggests that the polymorphisms affected transcription and that other regulatory mechanisms affect production of TNF alpha protein . The effect of these two polymorphisms on TNF alpha mRNA production is stimulus dependent, with opposite effects observed for Gram-positive and Gram-negative stimuli. Infect Immun, 2003 Jun, 71(6), 3206 - 12 Mutation of luxS of Streptococcus pneumoniae affects virulence in a mouse model; Stroeher UH et al.; The LuxS protein is required for the biosynthesis of the type 2 autoinducer (AI-2), which is involved in quorum sensing in a wide range of bacterial species . We have determined the effects of a defined luxS mutation on the virulence of Streptococcus pneumoniae . Although the luxS mutant displayed reduced virulence relative to its wild-type parent, the type 2 strain D39, it was by no means avirulent in a mouse model . After intranasal administration, the luxS mutant was able to colonize the nasopharynx of the mouse as efficiently as the wild type . However, it was less able to spread from the nasopharynx to the lungs or the blood . Intraperitoneal coadministration studies indicated that the luxS mutant was less fit and was readily outcompeted by wild-type D39 . However, when administered on its own by this route, the mutant was able to proliferate and cause fatal systemic disease, albeit at a lower rate than the wild type . Western blot analysis of whole-cell lysates of the mutant and its parent did not reveal any differences in the levels of several well-characterized virulence proteins . However, analysis of Coomassie blue-stained protein profiles after separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that mutation of luxS had pleiotropic effects on protein expression in all cellular compartments . This is consistent with the product of luxS having a regulatory role in S . pneumoniae . This is the first report of a direct role for luxS (and by inference, AI-2) in the virulence of a gram-positive pathogen . However, the fact that mutagenesis of luxS does not completely attenuate S . pneumoniae has implications for the possible use of AI-2 antagonists for treatment of pneumococcal infections. Infect Immun, 2003 Jun, 71(6), 3028 - 33 A fluoroquinolone induces a novel mitogen-encoding bacteriophage in Streptococcus canis; Ingrey KT et al.; This study investigated whether the recently recognized emergence of canine streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis (NF) might be partly attributed to the use of fluoroquinolones to treat Streptococcus canis infections in dogs . Both mitomycin and the fluoroquinolone enrofloxacin caused bacteriophage-induced lysis of S . canis strain 34, an isolate from a case of canine STSS and NF . Fluoroquinolone-evoked, bacteriophage-induced lysis occurred over a range of concentrations similar to those that would occur after treatment of dogs with these agents . To search for a possible bacteriophage-encoded streptococcal superantigen gene(s), a library of the 36.5 (+/-1.1)-kb bacteriophage, designated phisc1, was made by ligating 3- to 7-kb Tsp5091-digested phisc1 fragments into an EcoRI-digested lambdaZapII vector . Recombinants were screened for mitogenic activity by using canine peripheral blood lymphocytes . Of 800 recombinants screened, 11 recombinants with mitogenic effects were identified, and their inserts were sequenced . The highest homology of 11.6 kb of sequenced phisc1 DNA was to the completely sequenced Streptococcus pneumoniae bacteriophage MM1 . Seven of the 11 phisc1 sequenced inserts contained a 552-bp open reading frame, scm, with 27% amino acid similarity to pokeweed (Phytolacca americana) mitogen . PCR showed this gene to be present in 22 of 23 S . canis isolates tested . Quantitative reverse transcription-PCR showed that bacteriophage induction was associated with a 58-fold enhancement of expression of this gene relative to that in a noninduced culture of a similar age . The presence of this gene on a fluoroquinolone-induced bacteriophage may explain the association observed between fluoroquinolone use in dogs and the development of canine STTS and NF. Antimicrob Agents Chemother, 2003 Jun, 47(6), 1984 - 7 Linezolid and vancomycin, alone and in combination with rifampin, compared with moxifloxacin against a multidrug-resistant and a vancomycin-tolerant Streptococcus pneumoniae strain in an in vitro pharmacodynamic model; Cha R et al.; Potential alternatives, including linezolid, adjunctive rifampin, and moxifloxacin, were evaluated against vancomycin-tolerant (P9802-020) and vancomycin-susceptible clinical isolates of Streptococcus pneumoniae in an in vitro pharmacodynamic model . Vancomycin exhibited maximal killing of 2-log(10) CFU/ml against P9802-020 . Linezolid, moxifloxacin, and linezolid plus rifampin exhibited 99.9% killing against both isolates . These alternatives should be considered for further evaluation against vancomycin-tolerant S . pneumoniae. Antimicrob Agents Chemother, 2003 Jun, 47(6), 1976 - 8 Lack of vancomycin tolerance in Streptococcus pneumoniae strains isolated in Barcelona, Spain, from 1999 to 2001; Ortega M et al.; To evaluate the incidence of vancomycin tolerance among Streptococcus pneumoniae isolates, we performed killing curve studies with 633 isolates . The penicillin MIC was > or = 0.12 mg/liter for 481 (76%) of the isolates . All strains were susceptible to vancomycin . Killing curve studies were performed with a vancomycin concentration of 2.5 mg/liter . The Tupelo strain was used for quality control . No vancomycin-tolerant strain was detected. Antimicrob Agents Chemother, 2003 Jun, 47(6), 1867 - 74 Antimicrobial resistance in respiratory tract Streptococcus pneumoniae isolates: results of the Canadian Respiratory Organism Susceptibility Study, 1997 to 2002; Zhanel GG et al.; A total of 6,991 unique patient isolates of Streptococcus pneumoniae were collected from October 1997 to June 2002 from 25 medical centers in 9 of the 10 Canadian provinces . Among these isolates, 20.2% were penicillin nonsusceptible, with 14.6% being penicillin intermediate (MIC, 0.12 to 1 microg/ml) and 5.6% being penicillin resistant (MIC, > or =2 microg/ml) . The proportion of high-level penicillin-resistant S . pneumoniae isolates increased from 2.4 to 13.8% over the last 3 years of the study, and the proportion of multidrug-resistant S . pneumoniae isolates increased from 2.7 to 8.8% over the 5-year period . Resistant rates (intermediate and resistant) among non-beta-lactam agents were as follows: macrolides, 9.6 to 9.9%; clindamycin, 3.8%; doxycycline, 5.5%; chloramphenicol, 3.9%; and trimethoprim-sulfamethoxazole, 19.0% . Rates of resistance to non-beta-lactam agents were higher among penicillin-resistant strains than among penicillin-susceptible strains . No resistance to vancomycin or linezolid was observed; however, 0.1% intermediate resistance to quinupristin-dalfopristin was observed . The rate of macrolide resistance (intermediate and resistant) increased from 7.9 to 11.1% over the 5 years . For the fluoroquinolones, the order of activity based on the MICs at which 50% of isolates are inhibited (MIC(50)s) and the MIC(90)s was gemifloxacin > clinafloxacin > trovafloxacin > moxifloxacin > grepafloxacin > gatifloxacin > levofloxacin > ciprofloxacin . The investigational compounds ABT-773 (MIC(90), 0.008 microg/ml), ABT-492 (MIC(90), 0.015 microg/ml), GAR-936 (tigecycline; MIC(90), 0.06 microg/ml), and BMS284756 (garenoxacin; MIC(90), 0.06 micro g/ml) displayed excellent activities . Despite decreases in the rates of antibiotic consumption in Canada over the 5-year period, the rates of both high-level penicillin-resistant and multidrug-resistant S . pneumoniae isolates are increasing in Canada. Antimicrob Agents Chemother, 2003 Jun, 47(6), 1777 - 83 Macrolide resistance by ribosomal mutation in clinical isolates of Streptococcus pneumoniae from the PROTEKT 1999-2000 study; Farrell DJ et al.; Sixteen (1.5%) of the 1,043 clinical macrolide-resistant Streptococcus pneumoniae isolates collected and analyzed in the 1999-2000 PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) study have resistance mechanisms other than rRNA methylation or efflux . We have determined the macrolide resistance mechanisms in all 16 isolates by sequencing the L4 and L22 riboprotein genes, plus relevant segments of the four genes for 23S rRNA, and the expression of mutant rRNAs was analyzed by primer extension . Isolates from Canada (n = 4), Japan (n = 3), and Australia (n = 1) were found to have an A2059G mutation in all four 23S rRNA alleles . The Japanese isolates additionally had a G95D mutation in riboprotein L22; all of these originated from the same collection center and were clonal . Three of the Canadian isolates were also clonal; the rest were not genetically related . Four German isolates had A2059G in one, two, and three 23S rRNA alleles and A2058G in two 23S rRNA alleles, respectively . An isolate from the United States had C2611G in three 23S rRNA alleles, one isolate from Poland had A2058G in three 23S rRNA alleles, one isolate from Turkey had A2058G in four 23S rRNA alleles, and one isolate from Canada had A2059G in two 23S rRNA alleles . Erythromycin and clindamycin resistance gradually increased with the number of A2059G alleles, whereas going from one to two mutant alleles caused sharp rises in the azithromycin, roxithromycin, and rokitamycin MICs . Comparisons of mutation dosage with rRNA expression indicates that not all alleles are equally expressed . Despite their high levels of macrolide resistance, all 16 isolates remained susceptible to the ketolide telithromycin (MICs, 0.015 to 0.25 microg/ml). Curr Infect Dis Rep, 2003 Jun, 5(3), 230 - 237 Drug-resistant Streptococcus pneumoniae in Community-acquired Pneumonia; Henry M et al.; The emergence of Streptococcus pneumoniae isolates resistant to not only penicillin, but to other antipneumococcal agents as well, has major public health implications . Drug-resistant S . pneumoniae are distributed worldwide, and resistance has become increasingly prevalent in the United States within the past decade . The relevance of resistance, particularly to the beta-lactams, to treatment outcome has been subject to debate . Pneumonia due to intermediate-level-resistant penicillin-resistant isolates of S . pneumoniae appears to be adequately treated by beta-lactam agents . Interpretation of resistance reports, which may be based on achievable cerebrospinal fluid levels of drug, may depend on the clinical setting, and efforts are underway to adjust breakpoints so that reports are more easily applicable to clinical practice . Infectious Diseases Society of America and American Thoracic Society guidelines, as well as others, for community-acquired pneumonia have addressed the impact of drug-resistant S . pneumoniae on antimicrobial selection. J Antibiot (Tokyo), 2003 Mar, 56(3), 226 - 31 Nocathiacins, new thiazolyl peptide antibiotics from Nocardia sp . I . Taxonomy, fermentation and biological activities; Li W et al.; Thiazolyl peptide antibiotics, nocathiacin I, II and III, were identified in a culture of Nocardia sp . WW-12651 (ATCC 202099) . They exhibit potent in vitro activity (ng/ml) against a wide spectrum of gram-positive bacteria, including multiple-drug resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), multi-drug resistant Enterococcus faecium (MREF) and fully penicillin-resistant Streptococcus pneumoniae (PRSP), and demonstrate excellent in vivo efficacy in a systemic Staphylococcus aureus infection mice model. J Int Acad Periodontol, 2003 Apr, 5(2), 35 - 40 Antibacterial activity of synthetic human B defensin-2 against periodontal bacteria; Mineshiba F et al.; The oral epithelium is continuously exposed to a variety of microbial challenges that can cause infectious diseases such as periodontal disease . Human B Defensin-2 (hBD-2) is a cationic antimicrobial peptide with low molecular weight, which is inducible from oral epithelial cells upon either bacterial infection or stimulation with inflammatory cytokines . This peptide has a broad antimicrobial spectrum that includes gram-positive bacteria, gram-negative bacteria, and fungi . Therefore, it is thought that hBD-2 plays an important role as one of natural immunities to bacterial infection . However, its activity is inhibited by body fluids such as serum . The aim of this study was to assess the antibacterial activity of synthetic hBD-2 against oral bacteria in the presence of saliva or serum . The antibacterial activity of synthetic hBD-2 was tested against Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Streptococcus mutans, and Escherichia coli . Antibacterial broth assay and diffusion assay were performed in vitro . The antibacterial activity of hBD-2 was approximately equal to that of minocycline at equimolar concentrations . Furthermore, the activity of hBD-2 remained at 60% in the presence of 80% saliva, whereas no activity remained in the presence of 20% serum . Our results suggest the possibility that synthetic hBD-2 could be useful to prevent infection by periodontal bacteria. An Sist Sanit Navar, 2003 Jan-Apr, 26(1), 27 - 33 {Resistance to penicillin and other antimicrobials in 103 clinical isolations of Streptococcus pneumoniae (2000-2001)}; Garcia-Irure JJ et al.; BACKGROUND: To determine in our hospital the sensitivity of isolations of Streptococcus pneumoniae to penicillin, as well as to analyse the association of resistance to penicillin and other antimicrobials and the activity of cefotaxime and cefepime in pencillin resistant strains of Streptococcus pneumoniae . METHODS: The sensitivity was determined on 103 isolations of Streptococcus pneumoniae, from clinical samples from the years 2000-2001, to penicillin, eritromycine, cloramfenicol, tetracycline, cotrimoxazol, cefotaxime, cefepime and levofloxacine . RESULTS: Sixty-eight percent of the isolations were sensitive to penicillin, while some 32% of the isolated strains of Streptococcus pneumoniae were penicillin resistant, with 7.7% showing a high degree of resistance . Resistance to eritromycine, cloramfenicol, tetracycline, cotrimoxazol and levofloxacine was 38.8%; 9.7%; 20.4%; 25.2% and 2.9% respectively, increasing to values of 66.6%; 30.3%; 48.5%; 72.7% and 9.1% in the 33 penicillin resistant strains . Resistance to cefotaxime and cefepime was 9.7% and 10.6% respectively . CONCLUSIONS . A high percentage of strains of Streptococcus pneumoniae show some degree of resistance to penicillin, but with lower figures than in other studies carried out at a national level . Similarly, it was demonstrated that resistance to penicillin is significantly associated (p < 0.001) with resistance to all the antimicrobials studied, except for levofloxacine . The resistances to cefotaxime and cefepime were comparable, with less activity being observed in these when facing penicillin resistant strains of Streptococcus pneumoniae. Infez Med, 1999, 7(2), 113 - 118 {Complicated purulent meningitis as first manifestation of a hidden HIV disease}; Manfredi R et al.; A case report of severe Streptococcus pneumoniae meningitis, prompting the diagnosis of a concurrent occult HIV infection, is presented . Despite a favorable in vitro susceptibility profile of the isolated microbial strain and timely antibiotic treatment, our patient suffered from permanent neurogical sequelae (severe bilateral central hypacusia) . The role of penumococcal complications in the context of HIV disease and AIDS is rewieved in light of recent finding reported in the literature. Diabetes Res Clin Pract, 2003 Jun, 60(3), 213 - 6 Successful treatment of necrotizing fasciitis associated with diabetic nephropathy; Ogawa D et al.; A 50-year-old woman with a 15-year history of type 2 diabetes mellitus was admitted to our hospital due to high fever and a skin lesion with severe pain, swelling and a sensation of heat in the right thigh . Laboratory examination showed elevated C-reactive protein (CRP), thrombocytopenia, nephrotic syndrome and renal dysfunction . Her blood glucose level had been well controlled . Streptococcus agalactiae was detected in both the skin lesion and blood culture, and pathological examination revealed neutrophil infiltration in the fascia and muscle layer . The patient was diagnosed with necrotizing fasciitis, septic shock and disseminated intravascular coagulation . A combination therapy of antibiotics and surgical debridement resulted in the improvement of symptoms as supported by laboratory findings, and the skin lesion also showed improvement . Although group A streptococcus is well known to be implicated in the pathogenesis of necrotizing fasciitis, only S . agalactiae, belonging to group B streptococcus, was isolated from the tissue and blood cultures in this case . Although this organism is not virulent and rarely causes a necrotizing fasciitis, both the superficial fascial layer and underlying muscle were affected in this case . There have been only a few reports of necrotizing fasciitis due to S . agalactiae in patients with diabetes mellitus . Although the blood glucose level was well controlled in our patient, this disease might be caused by other factors, including diminished sense of touch and pain, abnormality of microcirculation and hypogammaglobulinemia due to nephrotic syndrome. FEMS Microbiol Lett, 2003 May 16, 222(1), 69 - 74 CNE, a collagen-binding protein of Streptococcus equi; Lannergard J et al.; Streptococcus equi subspecies equi is an important horse pathogenic bacterium causing a serious disease called strangles . Using bioinformatics we identified a gene denoted cne (gene encoding collagen-binding protein from S . equi) coding for a novel potential virulence factor of this species called protein CNE . The protein is composed of 657 amino acids and has the typical features found in cell surface-anchored proteins in Gram-positive bacteria . CNE displays amino acid sequence similarities to the previously well-studied collagen-binding protein CNA from Staphylococcus aureus, a proven virulence factor in septic arthritis . Based on similarity to CNA the structure of the mature CNE protein can be divided into an N-terminal A domain and a C-terminal B domain . The highest similarity between CNA and CNE is found in the A domains . The A domain in CNA is known to be the collagen-binding domain . Two parts of cne were amplified using polymerase chain reaction (PCR) and ligated into an expression vector, and recombinant CNE proteins were produced in Escherichia coli . The purified CNE proteins were shown to display collagen-binding activity in a Western ligand blot and to inhibit collagen binding to cells of subsp . equi and to CNE-coated microtitre wells . Furthermore, the A domain of CNE was sufficient for binding collagen, and was shown to compete for the same site on collagen as CNA in inhibition studies . Using PCR, the cne gene was detected in all studied strains of subsp . equi and S . equi subsp . zooepidemicus. J Pediatr, 2003 May, 142(5), 492 - 7 Intrapartum antibiotics and neonatal invasive infections caused by organisms other than group B streptococcus; Sinha A et al.; OBJECTIVES/STUDY DESIGN: Administration of group B streptococcal (GBS) antibiotic prophylaxis to women in labor has dramatically reduced the incidence of GBS neonatal disease, but there is little information on its impact on neonatal infections caused by other organisms . We conducted a nested case-control study to define the association between maternal intrapartum antibiotics and risk of neonatal non-GBS infection . RESULTS: In our study population, 114 of 13,224 infants had 115 non-GBS infections . The incidence of non-GBS neonatal infections fell during the study period, ranging from an attack rate of 9.6 per 1000 infants in 1990 to 1992 to 8.0 per 1000 infants in 1996 to 1998, although this trend was not statistically significant (P >.05) . The unadjusted association between neonatal infection and GBS prophylaxis was 0.89 (95% CI, 0.29, 2.6) and between neonatal infection and maternal intrapartum antibiotic due to any cause was 1.3 (95% CI, 0.65, 2.8) . CONCLUSIONS: The current policy of GBS maternal prophylaxis does not appear to convey excess risk of non-GBS infection to neonates. Presse Med, 2003 Apr 5, 32(13 Pt 2), S17 - 20 {Contribution of linezolid to the treatment of complicated infections of the skin and soft tissues}; Gauzit R; THREE GROUPS OF INCREASING SEVERITY: According to the 2000 consensus conference, bacterial infections of the skin and soft tissues can be classified in three categories of increasing severity: bacterial dermo-hypodermal infections, bacterial dermo-hypodermal necrotizing infections, necrotizing fasciitis . The last two categories are medicosurgical emergency conditions requiring repeated surgical debridement and probabilistic antibiotic therapy . LINEZOLID: The clinical efficacy of linezolid in bacterial infections of the skin and soft tissues is comparable to that of oxacillin/dicloxacillin . Several arguments (frequent implication of Streptococcus pyogenes and Staphylococcus aureus, well-adapted spectrum, changing resistance pattern of Gram-positive cocci, efficacy against associated bacteriemia, favorable kinetics and diffusion data in cutaneous tissues) argue in favor of the use of linezolid in infections of the skin and soft tissues Presse Med, 2003 Apr 5, 32(13 Pt 2), S5 - 8 {Epidemiology of Gram-positive infections in France: changing resistance}; Lepape A; CONTRIBUTION OF CLINICAL EPIDEMIOLOGY: Clinical epidemiology goes beyond simply counting cases of resistance . The goal is to collect clinical data contributing to an explication of epidemiological observations enabling a classification into 4 types of resistance . GRAM POSITIVE BACTERIA: Depending on the specialty, Gram positive bacteria are the cause of a variable percentage of clinical infections . In oncology and hematology, Gram-positive infections appear to be on the rise due to the increase in the number of coagulase-negative staphylococcal infections . The percentage appears to be unchanged in intensive care . Community-acquired streptococcal infections include a growing number caused by Streptococcus viridans, with the development of resistance and an aggravation of Streptococcus pneumoniae resistance . Nosocomial Gram-positive infections show that the increase in the number of meticillin-resistant Staphylococcus aureus infections is slowing down with the emergence of exceptional Staphylococcus aureus strains exhibiting intermediary resistance to glycopeptides . STREPTOCOCCUS VIRIDANS: Isolation of Streptococcus viridans is becoming increasingly frequent, particularly in immunodepressed patients or in patients with surgical conditions such as peritonitis . Several risk factors have been identified . In vitro glycopeptides and linezolide would have 100% activity against S . viridans . METICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (MRSA): Infections caused by MRSA strains are rather exceptional compared with simple colonization . All patients with suspected Staphylococcus aureus infections should not be treated as if they had a MRSA infection . STREPTOCOCCUS PNEUMONIA: Beta-lactame resistant pneumococci have shown some progression. Infez Med, 2002 Dec, 10(4), 213 - 9 {Pharyngotonsillitis caused by Streptococcus pyogenes: clinical and epidemiological aspects and resistance phenotypes towards macrolides}; Crotti D et al.; During 2001 we analyzed 1730 pharyngeal swabs for S . pyogenes (SGA): 1142 children (0-10 years old), 132 adolescent subjects (11-17 years old), and 456 adults (18 or more years old) . 994 subjects (664 children, 85 adolescent ones, 245 adults) had acute pharyngotonsillitis . In this last group we observed 321 positivities (32.3 %) for SGA: 40.4 % among children, 24.7 % among adolescent people, 13.1 % among adults . The pharyngotonsillitis prevailed during winter and spring . The resistances (R) towards erythromycin were 27.7 % (89 cases), and among children 30.6 % (82 cases), towards clyndamicin 15.3 % (49 cases, and 17.2 %, 46 cases, among children), towards rokytamicin 11.8 % (38 cases, and 13.1 %, 35 cases, among children) . These were the phenotypes of R to erythromycin: 25.8 % M-phenotype, 19.1 % inducible (iMLS), 55.1 % constitutive (cMLS); among children respectively 25.6 %, 18.3 % and 53.7 % . Increased resistances towards 16-C macrolides, increased resistances of cMLS to erythromycin, and the persistence of R to 14-C macrolides around 30 % are discussed. Respirology, 2003 Jun, 8(2), 208 - 12 Prevalence and clinical significance of community-acquired penicillin-resistant pneumococcal pneumonia in Thailand; Sangthawan P et al.; OBJECTIVE: The study aimed to evaluate the prevalence, clinical significance and outcome of community-acquired penicillin-resistant Streptococcus pneumoniae (PRSP) pneumonia in Thailand . METHODOLOGY: We conducted a prospective study in culture-proven pneumococcal pneumonia . Pneumococci were defined as susceptible, intermediate resistance and high resistance according to the definitions of the United States National Committee for Clinical Laboratory Standards (NCCLS) . RESULTS: Forty-six consecutive patients were enrolled . Of the S . pneumoniae isolates collected, 41.3% were resistant to penicillin (37% intermediate resistance and 4.3% high resistance) . Resistance to other antibiotics was 13% to ceftriaxone (8.7% intermediate resistance and 4.3% high resistance), 34.8% to erythromycin, 39.1% to tetracycline, 26.1% to chloramphenicol, and 43.5% to trimethoprim -sulfamethoxazole . Prior antibiotic use within 3 months was significantly associated with resistance to penicillin . The overall mortality of pneumococcal pneumonia was 26.1% . Multilobar involvement and requirement for mechanical ventilation proved to be associated with mortality . However, resistance to penicillin or ceftriaxone was not associated with death . CONCLUSIONS: According to the US NCCLS guidelines, we found a high prevalence of drug-resistant S . pneumoniae in Thai patients with community-acquired pneumonia . Prior antibiotic use was significantly associated with penicillin resistance . However, the outcome was not related to in vitro penicillin susceptibility of S . pneumoniae isolated from the patients. Oral Microbiol Immunol, 2003 Jun, 18(3), 156 - 9 PCR method is essential for detecting Mycobacterium tuberculosis in oral cavity samples; Eguchi J et al.; Tuberculosis is a re-emerging infectious disease, and infection by Mycobacterium tuberculosis has been increasing in immunocompromised hosts, including elderly persons . M . tuberculosis-infected persons may receive dental treatment . To evaluate the risk of M . tuberculosis infection in dental clinics, we examined the detection rates of M . tuberculosis in sample of mixed saliva, dental plaque, extracted teeth, caries lesions, and denture plaque by nested polymerase chain reaction (PCR) . The detection rates by PCR in samples from mixed saliva, dental plaque, caries lesions and denture plaque obtained from tuberculosis patients were 98.0%, 92.0%, 89.0%, and 100%, respectively . The detection rates by the culture method were 17.3%, 2.0%, 0%, and 0%, respectively . M . tuberculosis also was detected from the nontuberculous mycobacteria-infected group . Strains of Actinomyces naeslundii, Porphyromonas gingivalis, and Fusobacterium nucleatum inhibited the growth of clinical strains of M . tuberculosis, but strains of Streptococcus mutans, Streptococcus sanguinis, and Actinobacillus actinomycetemcomitans did not . The present study concludes that the PCR method is essential for detecting M . tuberculosis in oral samples. Immunol Cell Biol, 2003 Jun, 81(3), 192 - 5 FcgammaRIIA polymorphisms in Streptococcus pneumoniae infection; Yuan FF et al.; Invasive pneumococcal disease continues to be a major cause of morbidity and mortality among children and adults worldwide . Effective host defence against Streptococcus pneumoniae depends on immunoglobulin G-mediated phagocytosis of the bacteria and it has been shown in vitro that the FcgammaRIIA polymorphism (FcgammaRIIA-R131 vs FcgammaRIIA-H131) determines the capacity of immunoglobulin G2-mediated phagocytosis via this receptor . In this study, we evaluated FcgammaRIIA polymorphisms in children with pneumococcal sepsis and a number of control groups in order to investigate a possible association of FcgammaRIIA genotypes with Streptococcus pneumoniae infection . The distribution of the genotypes differed in these populations . The frequency of homozygosity for FcgammaRIIA-R/R131 in the patients was significantly higher than that in the healthy random donor population (43%vs 21%, P < 0.05) . The frequencies of FcgammaRIIA-H/H131 were similar among all groups of individuals, while the incidence of the heterozygous FcgammaRIIA-R/H131 was lower (35%vs 52%, P < 0.05) . Thus, it appears that the FcgammaRIIA-H131 polymorphic form, even in the heterozygous form, may be protective for pneumococcal sepsis and children with FcgammaRIIA-R/R131 genotype could be more at risk of infection with invasive Streptococcus pneu-moniae. Eur J Biochem, 2003 May, 270(10), 2157 - 62 A unique variant of streptococcal group O-antigen (C-polysaccharide) that lacks phosphocholine; Bergstrom N et al.; Streptococcus mitis strain SK598, which represents a subgroup of biovar 1, possesses a unique variant of the C-polysaccharide found in the cell wall of all strains of Streptococcus pneumoniae and in some strains of S . mitis . This new variant lacks the choline methyl groups in contrast to the previously characterized forms of C-polysaccharide, which all contain one or two choline residues per repeat . The following structure of the repeating unit of the SK598 polysaccharide was established: where AAT is 2-acetamido-4-amino-2,4,6-trideoxy-d-galactose . This structure is identical to the double choline-substituted form of C-polysaccharide, except that it is substituted with ethanolamine instead of choline . This extends the number of recognized C-polysaccharide variants to four. Birth, 2003 Jun, 30(2), 116 - 23 Taking antenatal group B Streptococcus seriously: women's experiences of screening and perceptions of risk; Darbyshire P et al.; BACKGROUND: Early-onset group B streptococcal disease is a serious cause of neonatal morbidity and mortality . Although screening protocols for group B streptococcus are common, little is known of women's perceptions of this screening and the disease itself . The purpose of this study was to gain an understanding of women's experiences, knowledge, and perceptions about this bacteria and its screening . METHODS: Nine focus group interviews with 35 women explored their experiences and understanding of group B streptococcus screening . Transcribed interview data were interpreted to identify and articulate the women's experiences . RESULTS: Most women had little knowledge or understanding of group B streptococcus, obtaining their information largely from the stories or experiences of friends or family . Women struggled to understand the meaning and implications, both physical and "moral," of the disease for their baby and for themselves, clearly indicating both the subjective and statistical importance of the concept of risk for pregnant women . CONCLUSIONS: Group B streptococcus continues to be poorly understood by pregnant women who try to understand and weigh up its risks and implications so as to make the best decisions about screening . The women participated in screening ultimately, however, since it was seen to be patently "best for baby," relatively easy for them to undergo, and part of routine antenatal care. J Infect Dis, 2003 Jun 1, 187(11), 1694 - 703 Epub 2003 May 15. Contribution of protein G-related alpha2-macroglobulin-binding protein to bacterial virulence in a mouse skin model of group A streptococcal infection; Toppel AW et al.; Protein G-related alpha(2)-macroglobulin-binding (GRAB) protein is a cell wall-attached determinant of group A streptococcus (GAS) that interacts with the human protease inhibitor alpha(2)-macroglobulin (alpha(2)-M) . Of 86 clinical isolates tested, 23% could bind alpha(2)-M . However, all strains tested contained the grab gene . High levels of anti-GRAB antibodies were found in the serum of convalescent GAS-infected patients, a finding that indicates that this protein is expressed during the infection process . Among the alpha(2)-M-binding strains, 80% were skin isolates, and 20% were throat isolates, findings that suggest that the skin environment is a preferential site for expression of alpha(2)-M-binding activity . To test this possibility, we determined the role of GRAB in a mouse model of GAS skin infection . The wild-type strain KTL3, which interacts with alpha(2)-M, showed high virulence . The isogenic mutant of KTL3, MR4, devoid of surface-bound GRAB, was attenuated in virulence, compared with the wild-type strain . Thus, mice infected with MR4 survived longer, developed smaller skin lesions, and exhibited lower levels of bacterial dissemination than did those infected with KTL3 . These results emphasize the role of GRAB as a virulence factor of GAS. J Infect Dis, 2003 Jun 1, 187(11), 1686 - 93 Epub 2003 May 12. Role of leukocyte immunoglobuin G receptors in vaccine-induced immunity to Streptococcus pneumoniae; Saeland E et al.; Members of the leukocyte immunoglobulin (Ig) G receptor (FcgammaR) family play a key role in antibody-mediated phagocytosis and can either enhance antigen presentation or down-modulate immune responses . We studied immune responses to a pneumococcal conjugate (pneumococcal polysaccharide serotype 1 {PPS1}-tetanus toxoid) and antibody-mediated protection in mice deficient for individual FcgammaRs and complement receptor 3 (CR3) . FcR gamma chain-deficient (FcR gamma chain(-/-)) mice, which lack expression of both FcgammaRI and III, had significantly lower anti-PPS1 IgG2b and IgG3 responses than did wild-type mice, whereas FcgammaRII-deficient (FcgammaRII(-/-)) mice had significantly higher IgG2a and IgG3 titers . Wild-type and FcgammaRII(-/-) mice were protected against infection with pneumococcal serotype 1, whereas immunized FcR gamma chain(-/-) and FcgammaRIII-deficient mice were not . Immunized CR3-deficient mice were protected against disease, and complement depletion had little effect on protection . These data indicate that activatory leukocyte FcgammaR, but not FcgammaRII (a murine homologue of human FcgammaRIIb), contributes to IgG-mediated protection against pneumococcal disease. J Mol Model (Online), 2003 Jun, 9(3), 153 - 8 Epub 2003 May 15. Structural analysis of the functional influence of the surface peptide Gtf-P1 on Streptococcus mutans glucosyltransferase C activity; Chia JS et al.; Glucosyltransferases (GtfB/C/D) in Streptococcus mutans are responsible for synthesizing water-insoluble and water-soluble glucans from sucrose and play very crucial roles in the formation of dental plaque . A monoclonal antibody against a 19-mer peptide fragment named Gtf-P1 was found in GtfC to reduce the enzyme activity to 50% . However, a similar experiment suggested almost unchanged activity in GtfD, despite of the very high sequence homology between the two enzymes . No further details are yet available to elucidate the biochemical mechanism responsible for such discrimination . For a better understanding of the catalytic behavior of these glucosyltransferases, structural and functional analyses were performed . First, the exact epitope was identified to specify the residue(s) required for monoclonal antibody recognition . The results suggest that the discrimination is determined solely by single residue substitution . Second, based on a combined sequence and secondary structure alignment against known crystal structure of segments from closely related proteins, a three-dimensional homology model for GtfC was built . Structural analysis for the region communicating between Gtf-P1 and the catalytic triad revealed the possibility for an "en bloc" movement of hydrophobic residues, which may transduce the functional influence on enzyme activity from the surface of molecule into the proximity of the active site . Figure Side chain interactions between Gtf-P1 and catalytic Asp-477 in GtfC . Calpha-tracing of GtfC with the two crucial peptides (Gtf-P1, orange; Gtf-P2, blue) and the catalytic triad residues ( red) highlighted to show their relative spatial organization . Side chains for the residues are also depicted according to their atom types . The structure is viewed with the barrel opening facing down Rev Esp Quimioter, 2003 Mar, 16(1), 61 - 4 {Susceptibility of Streptococcus pyogenes to macrolides and quinolones in Guadalajara, Spain}; Rodriguez-Zurita ME et al.; We carried out a retrospective study of the susceptibility of 104 Streptococcus pyogenes strains, which were isolated in 2000 and 2001 from clinical samples of different origins, to penicillin, erythromycin, clindamycin, ofloxacin and levofloxacin . The susceptibility testing was performed using the agar difusion method according to the guidelines of the NCCLS . All of the isolates showed susceptibility to penicillin and clindamycin . However, we detected 11 strains that were resistant to erythromycin (10.6%) and 4 strains resistant to ofloxacin (3.8%) . We studied the resistance phenotypes of macrolides and lincosamides using erythromycin and clindamycin discs . Nine of the eleven strains that were resistant to erythromycin showed an M phenotype, while the remaining two showed inducible resistance to clindamycin, thus suggesting an MLS(B) inducible phenotype . No strains with constitutive resistance to erythromycin or clindamycin (MLS(B) constitutive phenotype) were identified . While penicillin is still uniformly active against S . pyogenes, in Guadalajara, there are 10.6% strains that are resistant to 14- and 15-atoms macrolides. Rev Esp Quimioter, 2003 Mar, 16(1), 58 - 60 {Susceptibility of Streptococcus pyogenes isolates from pharyngeal exudates in Cordoba (Spain)}; Gordillo RM et al.; Streptococcus pyogenes is an important human pathogen . Betalactams are still the drug of choice for the treatment of infections caused by this microorganism . In recent years an increase in the use of macrolides for initial treatment in respiratory infections has been observed; consequently, the number of macrolide-resistant isolates has also increased . We investigated the susceptibility of S . pyogenes to penicillin, erythromycin, clarithromycin and clindamycin in Cordoba during 2000, 2001 and the first 6 months of 2002 . We obtained 100 isolates of S . pyogenes from 1232 pharyngeal exudates, all of which were susceptible to penicillin and 39 of which were resistant to erythromycin and clarithromycin . Twenty-six of these 39 isolates were susceptible to clindamycin. Arch Oral Biol, 2003 Jun, 48(6), 431 - 8 Acid diffusion through extracellular polysaccharides produced by various mutants of Streptococcus mutans; Hata S et al.; Mutants of Streptococcus mutans V403, constructed by allelic exchange and altered in their capacity to produce enzymes involved in the production of extracellular polysaccharides from sucrose, were used to study the role of glucans and fructans in the diffusion of ions through cell concentrates . A 4.0mm diameter, 0.75 mm deep diffusion chamber with an ion-sensitive field-effect transistor electrode positioned at the base was used to monitor the diffusion of hydronium ions from a sodium lactate buffer using cell concentrates prepared from bacteria grown in various concentrations of sucrose and glucose . The wild-type strain V403 produced at least seven times as much water-insoluble glucan (ISG) from sucrose as mutants deficient in various combinations of glucosyltransferase B (GTF B), GTF C, GTF D and fructosyltransferase . The fastest diffusion of hydronium ions occurred with sucrose-grown cell concentrates of strain V403, and the time of diffusion to the bottom of the chamber was approximately 2.3 times longer when this strain was grown in glucose . The speed of diffusion with glucose-grown V403 was similar to that obtained with each of the mutants . When cells of strain V403 grown in sucrose and glucose were mixed, increases in diffusion speed were found to be directly related to the proportion of sucrose-grown cells . The mixing of ISG with several strains of S . mutans revealed that increases in diffusion speed were directly related to the quantity of ISG added. Crit Rev Biochem Mol Biol, 2003, 38(2), 143 - 68 Analysis of structure and function of putative surface-exposed proteins encoded in the Streptococcus pneumoniae genome: a bioinformatics-based approach to vaccine and drug design; Rigden DJ et al.; Streptococcus pneumoniae is the most common cause of fatal community-acquired pneumonia, middle ear infection, and meningitis . The prevention and treatment of this infection have become a top priority for the medical-scientific community . The present polysaccharide-based vaccine used to immunize susceptible hosts is only approximately 60% effective and is ineffective in children younger than 2 years of age . The new conjugate vaccine, based on the engineered diphtheria toxin coupled to polysaccharide antigens . is approved only for use in children under 2 years of age to treat invasive disease . While penicillin is the drug of choice to treat infections secondary to S . pneumoniae, increasing numbers of bacterial strains are resistant to penicillin as well as to broad spectrum antibiotics such as vancomycin . Thus, there is a need to identify new strategies to prevent and treat diseases caused by to S . pneumoniae . In this article, we summarize the utilization of the recently available S . pneumoniae genomic information in order to identify and characterize novel proteins likely located on the surface of this Gram-positive pathogenic bacterium . Because only a limited number of surface proteins of S . pneumoniae have been characterized to date, this information provides new insights into the pathogenesis of this organism as well as highlights possible avenues for its treatment and/or prevention in the future . The review is divided into two sections . First, we brietly summarize current information about known surface-exposed proteins of S . pneumoniae . This is followed by the illustration of procedures for the identification of new putative surface-exposed proteins . These have signal peptides required for their extra-cytoplasmic transport and/or additional signature sequences . Some of these will be S . pneumoniae virulence factors . The signature sequences we have chosen are those leading to protein binding to choline present on the bacterial surface, attachment to peptidoglycan of the cell wall, or anchoring to lipids of the cytoplasmic membrane . All these signatures are indicative of binding of proteins to the surface of this organism . Secondly, we illustrate the application of bioinformatics and modeling tools to these selected proteins in order to provide information about their likely functions and preliminary three-dimensional structure models . The focal point of the analysis of these proteins, their sequences, and structures is the evaluation of their antigenic properties and possible roles in pathogenicity . The information obtained from the genome analysis will be instrumental in the development of a more effective prophylactic and/or therapeutic agents to prevent and to treat infections due to S . pneumoniae. Pediatr Crit Care Med, 2003 Apr, 4(2), 170 - 5 Elevated cerebrospinal fluid levels of glutamate in children with bacterial meningitis as a predictor of the development of seizures or other adverse outcomes; Ma W et al.; OBJECTIVE: Evaluation of elevated cerebrospinal fluid levels of glutamate in children with bacterial meningitis as a predictor of seizures or other adverse outcomes . DESIGN: Prospective cohort study with controls . SETTING: A 36-bed pediatric intensive care unit and primary pediatric referral center . PATIENTS: From 1999 to 2001, a total of 55 patients, between the ages of 0 and 18 yrs, with lumbar punctures performed for suspected meningitis . MEASUREMENTS AND MAIN RESULTS: A total of 23 patients had bacterial meningitis confirmed by cerebrospinal fluid/blood culture and elevated cerebrospinal fluid white blood cell counts, and 32 patients, who tested negative, were included as controls . The median age for the patients with meningitis was 1.0 yr (range, 0.0-15.2 yrs), and in the culture-negative group (control group), the median age was 0.3 yrs (range, 0.0-17.0 yrs) . The average cerebrospinal fluid white blood cell count was 2707 +/- 3897 in the group with bacterial infection, whereas in the control group, the average was 148 +/- 259 (p < .01) . Patients with bacterial meningitis had a mean cerebrospinal fluid glutamate level of 60.5 +/- 88.4 mol/L, whereas the mean cerebrospinal fluid glutamate level in the control group was 4.9 +/- 11.0 mol/L (p < .01) . However, only 10 of 23 children with bacterial meningitis had a second lumbar puncture performed during the study . There was no correlation between the cerebrospinal fluid white blood cell count and cerebrospinal fluid glutamate levels in either the study or control patients . None of the control patients developed seizures or neurologic deficits, despite some patients having elevated glutamate levels . However, four patients with bacterial meningitis developed seizures after admission to the hospital, and ten were discharged with at least some neurologic sequelae attributable to their infection . Two out of the three who developed seizures and had a repeat lumbar puncture demonstrated persistent elevation of cerebrospinal fluid glutamate levels . In addition, 70% of patients (7 of 10) with Streptococcus pneumoniae meningitis developed neurologic complications (p = .04) . CONCLUSIONS: Bacterial meningitis in children causes an increase in cerebrospinal fluid glutamate that in many cases persists over time . However, in this limited study, neither higher nor persistent elevation of cerebrospinal fluid glutamate levels is predictive of which patients might develop seizures or other apparent immediate adverse outcomes after invasive infection . The responsible organism seems to have far more significance in predicting the development of adverse sequelae. Proteomics, 2003 May, 3(5), 627 - 46 Cellular and extracellular proteome analysis of Streptococcus mutans grown in a chemostat; Len AC et al.; The oral pathogen, Streptococcus mutans, was grown under glucose limitation in a chemostat at pH 7.0 and a dilution rate of 0.1 h(-1) to mimic the conditions prevailing in a healthy human oral cavity in between meal times . Solubilized cellular and extracellular proteins were separated by two-dimensional gel electrophoresis (2-DE) and, following tryptic digestion, 421 protein spots analyzed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry or electrospray ionization-tandem mass spectrometry . Analyses of the mass spectral data showed that the proteins matched the translation products of 200 different open reading frames (ORFs) deduced from contigs of the S . mutans UA159 genome and thus represented proteins derived from approximately 11% of the total ORFs of the bacterium . Of the identified proteins, 172 (including one surface protein) were characterized in the cellular fraction, and the remaining 28 (including two surface proteins) were uniquely identified from the culture fluid . The expression and therefore the existence of 30 proteins previously designated as 'hypothetical' or with no known function was confirmed . 2-DE of whole cell lysates revealed only a single intrinsic membrane protein . This is consistent with proteomic analyses of other Gram-positive bacteria where hydrophilic proteins represent the vast majority of those characterized. J Antimicrob Chemother, 2003 Jun, 51(6), 1431 - 4 Epub 2003 May 13. Intrapulmonary penetration of linezolid; Honeybourne D et al.; OBJECTIVE: This study was designed to measure the concentrations of linezolid in bronchial mucosa, pulmonary macrophages and epithelial lining fluid and to compare them with simultaneous blood levels . METHODS: Ten adult patients undergoing bronchoscopy for diagnostic purposes were given oral linezolid at a dosage of 600 mg twice a day for a total of six doses . Patients with active lung infection were excluded from the study . Flexible bronchoscopy was carried out between 2 and 8 h after the last dose of linezolid . Bronchial biopsies and bronchoalveolar lavage were carried out and a simultaneous blood sample obtained . Linezolid levels were measured using high-performance liquid chromatography (HPLC) . RESULTS: Mean concentrations of linezolid were 13.4 mg/L in serum, 10.7 mg/kg in mucosa, 8.1 mg/L in alveolar macrophages and 25.1 mg/L in epithelial lining fluid . The mean site/serum concentration ratios were 0.79 for bronchial mucosa, 0.71 for macrophages and 8.35 for epithelial lining fluid . CONCLUSIONS: The MIC90 (< or =4 mg/L) of linezolid for Staphylococcus aureus and Streptococcus pneumoniae was exceeded in serum and bronchial mucosa in all subjects, in epithelial lining fluid in nine subjects and in macrophages in six subjects. Surg Infect (Larchmt), 2003 Spring, 4(1), 29 - 35 Pathogenesis of posttraumatic empyema: the impact of pneumonia on pleural space infections; Hoth JJ et al.; BACKGROUND: Thoracic empyema may result either from primary pneumonic sources or intraabdominal sources of infection that seed the pleural space secondarily . In patients with thoracostomy tubes, empyema may result when blood in the pleural space becomes contaminated during tube insertion . To elucidate the cause of posttraumatic empyema, preoperative bronchoalveolar lavage (BAL)/sputum cultures obtained from patients with posttraumatic empyema were compared with cultures obtained at the time of decortication . MATERIALS AND METHODS: A retrospective study was conducted of trauma patients who developed empyema and underwent either video-assisted thoracoscopy or thoracotomy with decortication following blunt or penetrating trauma . At our level I trauma center, we studied all empyema cases diagnosed from November, 1998 to July, 2001 . Data collection included patient demographics, injuries sustained, preoperative BAL/sputum cultures, and culture data obtained at the time of decortication . All BAL/sputum cultures were performed no more than 5 days prior to decortication . RESULTS: Thirty-seven patients (26 blunt/11 penetrating) were identified . No patients had concurrent intra-abdominal sources of infection . All patients had at least one chest tube placed prior to decortication . Preoperative respiratory cultures (BAL/sputum) were obtained in 34 patients . The most common organisms isolated were Staphylococcus aureus in six patients (18%) and Hemophilus influenzae in six patients (18%) . Intraoperative cultures were obtained in all 37 patients, with the most common organism being S . aureus isolated in 22 patients (60%) . Interestingly, a correlation between preoperative BAL/sputum and intraoperative cultures was found in only seven of the 34 patients (21%) who had concomitant respiratory and pleural cultures . Cultures positive for S . aureus were isolated from five patients, Streptococcus pneumoniae from one patient, and Pseudomonas aeruginosa from one patient . CONCLUSION: Little correlation existed between preoperative BAL/sputum cultures and intraoperative cultures in this series of patients with posttraumatic empyema . This suggests that the causation is most often not a parapneumonic process . Furthermore, since S . aureus was the most common organism recovered from empyema, the source was more likely from inoculation of the pleural space by the injury itself or by tube thoracostomy. West Afr J Med, 2002 Jul-Sep, 21(3), 233 - 6 Nasopharyngeal carriage and susceptibility patterns of Streptococcus pneumoniae in Kumasi, Ghana; Denno DM et al.; Penicillin resistant Streptococcus pneunmoniae poses an increasing problem in paediatrics, particularly in less developed countries . Outside of South Africa, little is known about S . pneumoniae susceptibilities in Sub-Saharan Africa . The objective of this study was to determine the prevalence of pneumococcal colonization and antimicrobial susceptibility among children in urban Ghana . METHODS: Nasopharyngeal pneumococcal colonization was examined in 311 children attending a polyclinic for sick children and an immunization clinic in Kumasi, Ghana . Isolates were tested for antibiotic susceptibility to penicillin, tetracycline, erythromycin, chloramphenicol, cefuroxime, cefotaxime, ceftriaxone, and trimethoprim-sulfamethoxazole . RESULTS: Over half (51.4%) of subjects were colonized with S . pneumoniae and 17% of isolates were resistant to penicillin, all demonstrating intermediate resistance . S . pneumoniae strains were also frequently resistant to trimethoprim-sulfamethoxazole and tetracycline, less so to chloramphenicol and cefuroxime and were almost uniformly sensitive to cefotaxime, cefriaxone and erythromycin . CONCLUSIONS: Our study shows a high rate of pneumococcal nasopharyngeal colonization and a concerning level of penicillin resistance although at a less alarming rate than seen in some other countries . Multiple antimicrobial resistance was also noted especially among drugs readily available and commonly used . These data impact treatment choices in pneumococcal disease . Vaccine may play an important role in disease limitation . An effort to curtail the misuse of antibiotics, by prescription and otherwise, may prevent further increases in resistance rates. Brain Pathol, 2003 Apr, 13(2), 123 - 32 Morphological correlates of acute and permanent hearing loss during experimental pneumococcal meningitis; Klein M et al.; In patients with acute bacterial meningitis, hearing loss can be transient but is often permanent . The mechanisms underlying meningitis-associated hearing loss are not fully understood . Therefore, we investigated the morphological correlates of hearing loss in a rat model of pneumococcal meningitis . Transcutaneous intracisternal injection of Streptococcus pneumoniae resulted in a dose-dependent hearing loss (determined by auditory brainstem response audiometry), which was partially reversible during the acute stage . Nevertheless, a severe permanent hearing loss persisted until 2 weeks after infection . Suppurative labyrinthitis was accompanied by blood-labyrinth barrier disruption (determined by cochlear Evans blue extravasation), which correlated closely with hearing loss during the acute stage but not after recovery . Two weeks after infection, spiral ganglion neuronal density was markedly decreased and correlated with the severity of permanent hearing loss . Neuronal loss can be explained by the new finding of meningitis-associated spiral ganglion neuronal necrosis rather than apoptosis (determined by morphology, TUNEL staining, and immunohistochemistry). J Neuroimmunol, 2003 May, 138(1-2), 31 - 7 Interleukin-18 gene-deficient mice show enhanced defense and reduced inflammation during pneumococcal meningitis; Zwijnenburg PJ et al.; To determine the role of endogenous interleukin-18 (IL-18) in pneumococcal meningitis, meningitis was induced in IL-18 gene-deficient (IL-18(-/-)) and wild-type (WT) mice by intranasal inoculation of Streptococcus pneumoniae with hyaluronidase . Induction of meningitis resulted in an upregulation of both pro- and mature IL-18 in brain tissue in WT mice . IL-18(-/-) and WT mice were equally susceptible to develop meningitis after intranasal infection, yet IL-18(-/-) mice showed a prolonged survival and a suppressed inflammatory response, as reflected by a less profound inflammatory infiltrate around the meninges and lower concentrations of cytokines and chemokines in brain tissue . These findings suggest that endogenous IL-18 contributes to a detrimental inflammatory response during pneumococcal meningitis and that elimination of IL-18 may improve the outcome of this disease. Diagn Microbiol Infect Dis, 2003 May, 46(1), 77 - 80 Influence of patient age on the susceptibility patterns of Streptococcus pneumoniae isolates in North America (2000-2001): report from the SENTRY Antimicrobial Surveillance Program; Jones RN et al.; Risks of developing resistance in Streptococcus pneumoniae can be greatly influenced by antimicrobial use that is often dictated by patterns of prescribing at various patient ages . The results from the SENTRY Antimicrobial Surveillance Program (2000-2001; North America) were examined for differing susceptibility profiles (25 antimicrobials) indexed by five patient age groups . All MIC results were from reference methods performed in central laboratories . Pneumococcal resistance rates in the youngest patient group (0-5 years) were significantly (p < 0.05) higher for penicillin, other beta-lactams, macrolides, tetracyclines and trimethoprim/sulfamethoxazole . In contrast, fluoroquinolone resistance in S . pneumoniae was greatest in the patients >/= 65 years (1.4% resistance to gatifloxacin, levofloxacin and moxifloxacin), where use of this class has been escalating . Continued local and global surveillance of resistances in common respiratory tract pathogens such as S . pneumoniae appears to be prudent practice to guide effective chemotherapy. Med J Aust, 2003 May 19, 178(10), 505 - 7 Pneumococcal meningitis masquerading as subarachnoid haemorrhage; Chatterjee T et al.; A 43-year-old woman taking warfarin for past venous thrombosis presented with 4 days of flu-like symptoms and deterioration in level of consciousness . Computed tomography suggested subarachnoid haemorrhage, and magnetic resonance imaging showed widespread cerebral infarcts . However, these seemed out of proportion to the amount of haemorrhage, and lumbar puncture revealed meningitis caused by Streptococcus pneumoniae. Arch Pathol Lab Med, 2003 Jun, 127(6), 718 - 20 Comparison of direct selective versus nonselective agar media plus LIM broth enrichment for determination of group B streptococcus colonization status in pregnant women; Elsayed S et al.; CONTEXT: Group B streptococcus (GBS) is the most common cause of early-onset neonatal sepsis in developed countries, and determination of the GBS colonization status in pregnant patients near term is essential for the provision of prophylactic measures to prevent early-onset disease . OBJECTIVES: To determine if GBS recovery rates and/or result turnaround times for vaginal or combined vaginal/rectal swab specimens from pregnant patients near term are enhanced if swabs are inoculated initially onto selective versus nonselective agar media, in addition to the standard Centers for Disease Control and Prevention method . DESIGN: Prospective laboratory analysis . SETTING: Urban health region/centralized diagnostic microbiology laboratory . PATIENTS: Pregnant women presenting for routine obstetrical care and collection of vaginal or combined vaginal/rectal swab specimens for GBS testing at 35 to 37 weeks' gestation . INTERVENTION: Culture of specimens directly onto selective (5% sheep blood with colistin and nalidixic acid) or nonselective (5% sheep blood) agar media, in addition to LIM broth enrichment and terminal subculture . MAIN OUTCOME MEASURES: Group B streptococcus recovery rate and culture result turnaround time . RESULTS: A total of 639 specimens were tested, with 128 (20%) positive for GBS . Sixty-three isolates were recovered on direct agar media at 24 hours, of which 16 (12.5%) were isolated on selective plates only . An additional 38 isolates were recovered at 48 hours from direct plates . Twenty-seven (21.1%) isolates that failed to grow on direct plates were recovered from the LIM broth subculture only . Three (2.3%) isolates not recovered from LIM broths were detected at 48 hours on the direct selective (2 isolates) and nonselective (1 isolate) agar plates . A 24-hour result turnaround time was achieved for 63 (49.2%) and 47 (36.7%) of the 128 culture-positive specimens for direct selective and nonselective plates, respectively (chi2 = 76.63, P <.001) . CONCLUSIONS: Use of direct selective agar media, in addition to LIM broth enrichment, for the determination of the GBS colonization status in pregnant patients near term results in decreased turnaround time for reporting positive results. J Microbiol Immunol Infect, 2003 Mar, 36(1), 21 - 5 Predictive value of clinical features in differentiating group A beta-hemolytic streptococcal pharyngitis in children; Lin MH et al.; Identifying children with acute pharyngitis caused by group A beta-hemolytic Streptococcus (GABHS) is an important task for pediatricians . This study examined the value of certain clinical symptoms and signs in predicting a positive culture result . A total of 442 children who presented at the outpatient department with pharyngeal erythema were enrolled . The clinical features of patients with positive throat cultures for GABHS were compared to those with negative culture results . Throat cultures were positive for GABHS in 120 (27%) patients . Patients aged between 5 and 10 years had a higher prevalence of GABHS pharyngitis . Significant differences between the groups with and without GABHS pharyngitis were noted for the presence of sore throat (p < 0.001), tonsillar swelling (p < 0.001), anterior cervical adenopathy (p = 0.004), and scarlatiniform rash (p < 0.001), but not for the presence of fever, cough, rhinorrhea, abdominal pain, headache, tonsillar exudate, or palatal petechiae . Despite these strong associations, none of these symptoms or signs had both high sensitivity and specificity, and the positive predictive values of these individual findings were never greater than 50% . The results indicate that diagnosis based on clinical grounds alone is unreliable although there are certain individual symptoms and signs that are associated with GABHS pharyngitis . These symptoms and signs may be helpful in modifying estimates of probability of infection with GABHS . Throat cultures in suspected patients remain mandatory. J Dairy Sci, 2003 Apr, 86(4), 1233 - 9 Evaluation of the surveillance program of Streptococcus agalactiae in Danish dairy herds; Andersen HJ et al.; The aim of this study was to evaluate the Danish surveillance program of Streptococcus agalactiae in dairy herds with respect to 1) fluctuation over time of the presence of S . agalactiae in bulk tank milk, 2) sensitivity and specificity of the bacteriological method used, and 3) contamination of bulk tank milk samples with milk from other herds . From June to September 1996, bulk tank milk was sampled from 100 Danish dairy herds seven times, with intervals of 2 wk . The samples were examined for the presence of S . agalactiae by four different methods: 1) by the method approved for the program, 2) after ultrasonic treatment of the milk before examination, 3) after freezing down the milk before examination, and 4) after selective preparation of the milk . Selected strains of S . agalactiae were examined by restriction fragment length polymorphism of the gene encoding rRNA to discriminate between the isolates . Streptococcus agalactiae was found in eight of 96 herds in which S . agalactiae had never previously been found during the surveillance program . Streptococcus agalactiae was not found in all seven sampling rounds in any of the eight herds . Comparing the approved method with supplemental findings by the other methods, the estimated sensitivity was (95% confidence limits): 0.786 (0.628; 0.892) and the estimated specificity (95% confidence limits): 0.995 (0.985; 0.999) . Using all four methods on the same sample could increase the sensitivity, but by comparing the methods individually, there was no significant difference between any of them (P > 0.10) . In milk samples from three herds, the ribotype of S . agalactiae was the same as in milk from herds sampled just before; therefore, it could not be ruled out that cross-contamination could occur . Taking into account that S . agalactiae in bulk tank milk reflects the presence of S . agalactiae in at least one udder quarter, this investigation gives further reason to assume that S . agalactiae can be seen sporadically in several herds . A surveillance program based on annual bulk tank milk sample examinations will only detect a limited number of S . agalactiae infected herds . If the overall aim is to identify herds where the infection is established, annual bulk tank milk sample examinations combined with the information of number of colonies of S . agalactiae in the sample will be sufficient. Pharmacotherapy, 2003 May, 23(5), 638 - 42 Targeting bacterial virulence: the role of protein synthesis inhibitors in severe infections . Insights from the Society of Infectious Diseases Pharmacists; Coyle EA; Society of Infectious Diseases Pharmacists; Morbidity and mortality due to certain bacterial pathogens have not declined despite the availability of effective antimicrobial treatments . Staphylococcus aureus and Streptococcus pyogenes cause a number of serious infections, such as necrotizing fasciitis and toxic shock syndrome, which are associated with the release of bacterial toxins . Animal studies have demonstrated clindamycin, a protein synthesis inhibitor, to be more effective in treating these severe infections than other more susceptible antimicrobial treatments . Linezolid, another protein synthesis inhibitor, also has shown efficacy in in vitro studies . Human trials to validate the effects of antibiotic therapies on bacterial virulence have not been performed . Future animal and human studies are needed to help elucidate the immunomodulatory mechanisms of protein synthesis inhibitors in order to optimize antimicrobial treatment and decrease the morbidity and mortality associated with severe bacterial infections. Arch Mal Coeur Vaiss, 2003 Apr, 96(4), 300 - 4 {Infectious endocarditis . A study of 50 patients in a non-university hospital}; Cellarier G et al.; The authors report the results of a single centre study of 50 consecutive patients (average age 66 +/- 14 years; 36 men), admitted between 1992 and 2001 to a peripheral hospital for infectious endocarditis (IE) . The median interval to diagnosis was 57 days . There was an underlying cardiac disease in 52% of cases, usually valvular (42%) . The site of the IE was the mitral valve in 21 cases, the aortic valve in 19 cases, mitro-aortic valves in 5 cases, native tricuspid valves in 2 cases and pacing catheters in 4 cases (associated with valvular endocarditis in one patient) . The causal organism was usually a streptococcus (60%, including 28% of streptococcus bovis), or a staphylococcus (22%): no organism could be found in 7 patients . The average follow-up was 33 +/- 30 months: surgery was indicated in half the patients and 3 patients were turned down because of their poor general condition . In all, 34% of patients died (24% of their IE) in a median interval of 6 months, mainly from infectious or haemodynamic complications . Poor prognostic factors were: age > 70 years, "blind" antibiotic therapy, large-sized vegetations, embolism and renal failure . These data, comparable to the results observed in large series in the literature, underline the importance of multi-disciplinary management of IE and strict prophylaxis. Nat Med, 2003 Jun, 9(6), 736 - 43 Epub 2003 May 12. Pneumococcal vaccination decreases atherosclerotic lesion formation: molecular mimicry between Streptococcus pneumoniae and oxidized LDL; Binder CJ et al.; During the progression of atherosclerosis, autoantibodies are induced to epitopes of oxidized low-density lipoprotein (oxLDL) and active immunization of hypercholesterolemic mice with oxLDL ameliorates atherogenesis . We unexpectedly found that many autoantibodies to oxLDL derived from 'naive' atherosclerotic mice share complete genetic and structural identity with antibodies from the classic anti-phosphorylcholine B-cell clone, T15, which protect against common infectious pathogens, including pneumococci . To investigate whether in vivo exposure to pneumococci can affect atherogenesis, we immunized Ldlr(-/-) mice with Streptococcus pneumoniae . This induced high circulating levels of oxLDL-specific IgM and a persistent expansion of oxLDL-specific T15 IgM-secreting B cells primarily in the spleen, which were cross-reactive with pneumococcal determinants . Pneumococcal immunization decreased the extent of atherosclerosis, and plasma from these mice had an enhanced capacity to block the binding of oxLDL to macrophages . These studies show molecular mimicry between epitopes of oxLDL and S . pneumoniae and indicate that these immune responses can have beneficial effects. Caries Res, 2003 May-Jun, 37(3), 212 - 7 A new selective medium for Streptococcus mutans and the distribution of S . mutans and S . sobrinus and their serotypes in dental plaque; Hirasawa M et al.; A new selective medium (MS-MUT) was developed for the isolation of Streptococcus mutans from clinical specimens . The average growth recovery of S . mutans on MS-MUT medium was 72.4% of that on MS medium . Growth of Streptococcus sobrinus was significantly inhibited on the medium with an average recovery of 0.034% . In 103 subjects, S . MUTANS was detected at 58.3, 75.0 and 95.7% in the dental plaque of caries-free (CF), caries-inactive (CI) and caries-active (CA) subjects, respectively . S . sobrinus was detected in 8.3, 13.6 and 38.3% of CF, CI and CA subjects, respectively . S . sobrinus alone was detected in only 4.3% of CA subjects . The subjects in whom neither S . mutans nor S . sobrinus were detected were 41.6% in CF and 25.0% in CI . The most predominant serotype was C with a 67% detection rate . S . sobrinus, serotypes D or G were usually found together with S . mutans . Caries Res, 2003 May-Jun, 37(3), 190 - 3 The effect of variable energy input from a novel light source on the photoactivated bactericidal action of toluidine blue O on Streptococcus Mutans; Williams JA et al.; Although the combination of toluidine blue O (TBO) dye and laser light at a wavelength of 633 nm has a bactericidal effect, light from laboratory lasers can only be directed externally at a bacterial colony or suspension . In this study a novel delivery system guided the laser light to an 800-micrometer diameter spherical tip (an isotropic tip) from which light radiated producing a uniform sphere of light within the colony or suspension . The system was highly effective in killing TBO-treated Streptococcus mutans NCTC 10449 in stirred planktonic suspension, killing at least 10(9 )cfu/ml . Antibacterial action increased as the delivered energy dose increased . Energy doses of 1.8 J or more produced 100% kills and log reductions of 8-10 cfu/ml . Neither TBO dye nor light alone had a significant antibacterial effect under the experimental conditions used . The existence of a threshold energy, i.e . a minimum energy required before bactericidal action occurred, could not be demonstrated . Caries Res, 2003 May-Jun, 37(3), 185 - 9 Effect of a varnish containing chlorhexidine and thymol (Cervitec) on approximal caries in 13- to 16-year-old schoolchildren in a low caries area; Haukali G et al.; BACKGROUND: Previous studies on the effect of the chlorhexidine and thymol-containing varnish (Cervitec((R))) have consistently shown a reduction in STREPTOCOCCUS MUTANS, while the data on the caries-inhibiting effect are conflicting . AIM: To measure the effect of a chlorhexidine- and thymol-containing varnish (Cervitec) on approximal caries in a low caries population . MATERIAL: Eighty-five schoolchildren, 13 years of age, entered the study after being selected on the basis of bitewing radiographs . Children with at least one approximal lesion were included after informed consent . METHODS: The study was carried out as a double-blind, randomized controlled trial according to a split-mouth design using Cervitec on one side and a placebo varnish on the other side . All approximal surfaces between molars and premolars were treated every 3rd month . After 2 years new bitewing radiographs were taken . A total of 73 children completed the 2-year study . RESULTS: Neither the difference in number of new lesions between the Cervitec-treated and the placebo-treated side (d: -0.21; 95% CI: -0.57; 0.16) nor the mean difference in number of already existing lesions that progressed (d: -0.01; 95% CI: -0.33; 0.30) were statistically significant (paired t test; p > 0.05) . CONCLUSION: The results of our study do not indicate an effect of Cervitec on initiation or progression of approximal caries in a population with a low DMFS . Chest, 2003 May, 123(5), 1615 - 24 Community-acquired bloodstream infection in critically ill adult patients: impact of shock and inappropriate antibiotic therapy on survival; Valles J et al.; DESIGN: The objectives were to characterize the prognostic factors and evaluate the impact of inappropriate empiric antibiotic treatment and systemic response on the outcome of critically ill patients with community-acquired bloodstream infection (BSI) . PATIENTS: A prospective, multicenter, observational study was carried out in 339 patients admitted in 30 ICUs for BSI . RESULTS: Crude mortality was 41.5% . Septic shock was present in 184 patients (55%) . The pathogens most frequently associated with septic shock or death were Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae, which accounted for approximately half of the deaths . Antibiotic treatment was found to be inappropriate in 14.5% of episodes . Patients in septic shock with inappropriate treatment had a survival rate below 20% . Multivariate analysis identified a significant association between septic shock and four variables: age > or = 60 years (odds ratio {OR}, 1.96), previous corticosteroid therapy (OR, 2.58), leukopenia (OR, 2.32), and BSI secondary to intra-abdominal (OR, 2.38) and genitourinary tract (OR, 2.29) infections . The variables that independently predicted death at ICU admission were APACHE (acute physiology and chronic health evaluation) II score > or = 15 (OR, 2.42), development of septic shock (OR, 3.22), and inappropriate empiric antibiotic treatment (OR, 4.11) . This last variable was independently associated with an unknown source of sepsis (OR, 2.49) . Mortality attributable to inappropriate antibiotic treatment increased with the severity of illness at ICU admission (10.7% for APACHE II score < 15 and 41.8% for APACHE II score > or = 25, p < 0.01) . CONCLUSIONS: Inappropriate antimicrobial treatment is the most important influence on outcome in patients admitted to the ICU for community-acquired BSI, particularly in presence of septic shock or high degrees of severity . Initial broad-spectrum therapy should be prescribed to septic patients in whom the source is unknown or in those requiring vasopressors. Clin Immunol, 2003 Apr, 107(1), 20 - 9 Effects of multidose combination chemotherapy on the humoral immune system; Zandvoort A et al.; Patients receiving multidose combination chemotherapy are at risk for severe, life-threatening infections, caused by among others encapsulated bacteria like Streptococcus pneumoniae . The splenic marginal zone is essential in the initiation of immune responses to S . pneumoniae . We analyzed effects of multidose combination chemotherapy on B-cell subpopulations . Immune response capacity was evaluated by using Pneumovax (PPS) or Tetavax (TT) as antigenic challenge . Three days after finishing therapy, all B-cell subpopulations in bone marrow and spleen were severely reduced, including the mature marginal zone B-cell population . When analyzing the anti-PPS immune response capacity at 3 days after finishing therapy, we found that the IgM antibody levels did not differ significantly from control immunized rats . The IgG antibody levels were significantly lower compared to control immunized rats but still significantly higher compared to unimmunized rats . The depletion of marginal zone B cells by multidose combination chemotherapy most likely contributes to the prolonged period that patients are at risk for developing severe infections after chemotherapy, despite the capacity to generate sufficient antibody levels . It is conceivable that the local (temporary) loss of immunological memory, together with the supposed inability to generate a humoral response in a short time frame, plays an important role in this vulnerability. New Microbiol, 2003 Apr, 26(2), 187 - 92 Streptococcus pneumoniae nasopharyngeal colonization in young healthy children: rate of carriage, serotype distribution, and antibiotic resistance; Mosca A et al.; The nasopharyngeal colonization rate of Streptococcus pneumoniae and its antibiotic susceptibility was determined in a given population of 317 young children (ages 1-7 years) in the area of Bari, Italy . 18.29% of the cultures were positive for S . pneumoniae . 8.62% of the strains were intermediately resistant to penicillin . Erythromycin-(65.51%) and cotrimoxazole-(17.24%) resistance was also observed whereas all the strains resulted uniformely susceptible to cefotaxime and ceftriaxone . The high rate of nasopharyngeal carriage of Streptococcus pneumoniae along with the resistance to antibiotics widely used in the community suggests the importance of epidemiological surveillance as well as the application of new vaccine strategies. Nature, 2003 May 8, 423(6936), 177 - 81 Pathogenic bacteria attach to human fibronectin through a tandem beta-zipper; Schwarz-Linek U et al.; Staphylococcus aureus and Streptococcus pyogenes, two important human pathogens, target host fibronectin (Fn) in their adhesion to and invasion of host cells . Fibronectin-binding proteins (FnBPs), anchored in the bacterial cell wall, have multiple Fn-binding repeats in an unfolded region of the protein . The bacterium-binding site in the amino-terminal domain (1-5F1) of Fn contains five sequential Fn type 1 (F1) modules . Here we show the structure of a streptococcal (S . dysgalactiae) FnBP peptide (B3) in complex with the module pair 1F12F1 . This identifies 1F1- and 2F1-binding motifs in B3 that form additional antiparallel beta-strands on sequential F1 modules-the first example of a tandem beta-zipper . Sequence analyses of larger regions of FnBPs from S . pyogenes and S . aureus reveal a repeating pattern of F1-binding motifs that match the pattern of F1 modules in 1-5F1 of Fn . In the process of Fn-mediated invasion of host cells, therefore, the bacterial proteins seem to exploit the modular structure of Fn by forming extended tandem beta-zippers . This work is a vital step forward in explaining the full mechanism of the integrin-dependent FnBP-mediated invasion of host cells. Infez Med, 1999, 7(3), 187 - 191 {Streptococcus bovis as an opportunistic pathogen during advanced HIV disease}; Manfredi R et al.; Three rare case reports of HIV-related Streptococcus bovis bacteremia are described, and discussed on the basis of a literature review . The association with an advanced immunodeficiency, leukopenia-neutropenia, and liver cirrhosis is underlined as well as the possibility of multiple recurrences and the lack of apparent gastrointestinal lesions as risk factors. Infez Med, 1999, 7(3), 177 - 186 {Necrotizing fasciitis: case reports and review of the literature}; Di Gregorio P et al.; Necrotizing fasciitis is a rare, rapidly progressing infection affecting the superficial fascia and the subcutaneous tissue, accompanied by severe systemic toxicity and multiorgan failure . It is caused by aerobic and anaerobic bacteria, occasionally in a synergistic polymicrobial combination (Type I Necrotizing Fasciitis); in other cases group A -haemolitic Streptoccoccus is the organism responsible for the infection (Type II Necrotizing Fasciitis) . The infection often originates from small traumatic injuries or operative wounds and rapidly spreads especially in individuals with identifiable risk factors or immunocompromised patients . Sometimes necrotizing fasciitis occurs when no known portal of entry for bacteria is present . The increasing incidence of necrotizing fasciitis observed may reflect a resurgence of highly virulent mutant strains of group A beta-haemolitic Streptococcus . The pathogenesis, clinical features and treatment of the disease have been reviewed in the light of recent literature . We also report clinical data for four patients with necrotizing fasciitis . They show the importance of early diagnosis and rapid, aggressive and radical surgical intervention . High-dose broad-spectrum antibiotic therapy and intensive medical support are also required to avoid a fatal outcome. Chem Pharm Bull (Tokyo), 2003 May, 51(5), 494 - 8 Synthesis, characterization, and antibacterial activities of some rare Earth metal complexes of pipemidic acid; Yang L et al.; Eight new solid complexes of pipemidic acid (PPA) with trichlorizated rare earth metals LaCl(3), CeCl(3), PrCl(3), NdCl(3), SmCl(3), TbCl(3), DyCl(3), and YCl(3) have been synthesized . The complexes were characterized by elemental analyses, IR, NMR, and molar conductance measurements . The general formulas of the complexes are {M(PPA)(4)}Cl(3) (M=Ce(III), Pr(III), Nd(III), Sm(III), Tb(III), Dy(III), Y(III)), and {La(PPA)(4)Cl}Cl(2) . At the same time, the antibacterial activities of PPA and four of its complexes were tested . The results show that PPA and its complexes all have inhibitory action against bacteria of Escherichia coli, Bacillus subtilis, Streptococcus pneumoniae, and Pseudomonas aeruginosa but not Staphylococcus aureus . We compared their antibacterial activities and found that the antibacterial activity of {La(PPA)(4)Cl}Cl(2) against S . pneumoniae is much stronger than that of PPA and the other complexes. Bioorg Med Chem, 2003 May 29, 11(11), 2389 - 94 Synthesis of 9-oxime-11,12-carbamate ketolides through a novel N-deamination reaction of 11,12-hydrazonocarbamate ketolide; Denis A et al.; A series of 9-oxime-11,12-carbamate ketolides was synthesized for the first time through a key 11,12-hydrazonocarbamate intermediate that was first oximated and further deaminated to give the corresponding carbamate . The N-N bond cleavage was achieved through an original new reaction using glycoaldehyde dimer as deaminating reagent . The new compounds synthesized were shown to display improved antibacterial activities against Streptococcus pneumoniae and S . pyogenes resistant to erythromycin. J Vet Diagn Invest, 2003 May, 15(3), 295 - 7 Descriptive epidemiology of late-term abortions associated with the mare reproductive loss syndrome in central Kentucky; Cohen ND et al.; Epidemiological and pathological findings of 433 late-term abortions associated with the mare reproductive loss syndrome (MRLS) in central Kentucky were identified by reviewing the records of the University of Kentucky Livestock Diseases Diagnostic Center . The distribution of dates of abortion was clustered during a brief period of time, presumably from a simultaneous environmental exposure . The most common pathological findings were microscopic pulmonary lesions consisting of squamous epithelial cells present in alveoli with or without concurrent infiltration of inflammatory cells (neutrophils, macrophages, or monocytes) in the interstitium or within alveoli . Isolation of a non-beta-hemolytic Streptococcus (52% of fetuses) or an Actinobacillus sp . (19% of fetuses) was common . Placentitis or funisitis was identified in 44% of fetuses . No single pathological finding, however, was pathognomonic for MRLS-associated late-term abortion . This report describes the pathological findings characterizing the MRLS-associated abortion . A cause of MRLS could not be determined from necropsy findings. J Biomed Mater Res A, 2003 May 1, 65(2), 203 - 8 Antibacterial characteristics of newly developed amphiphilic lipids and DNA-lipid complexes against bacteria; Inoue Y et al.; The purpose of this study was to investigate the antibacterial activity of newly developed amphiphilic lipids and DNA/lipid complexes against two types of oral bacteria and two types of hospital infection bacteria . Nine amphiphilic lipids were quantitatively prepared from the reaction of n-alkyl alcohol, alpha-amino acids, and p-toluenesulfonic acid . Nine DNA-lipid complexes were prepared by the simple mixing of