Increased C5a receptor expression in sepsis.

Excessive production of the complement activation product C5a appears to be harmful during the development of sepsis in rodents. Little is known about the role of the C5a receptor (C5aR) and its presence in different organs during sepsis. Using the cecal ligation/puncture (CLP) model in mice, we show here that C5aR immunoreactivity was strikingly increased in lung, liver, kidney, and heart early in sepsis in both control and neutrophil-depleted mice. C5aR mRNA expression in these organs was also significantly increased during sepsis. Immunohistochemical analysis revealed patterns of increased C5aR expression in parenchymal cells in all four organs following CLP. Mice injected at the start of CLP with a blocking IgG to C5aR (alphaC5aR) showed dramatically improved survival when compared with animals receiving nonspecific IgG, as did mice injected with alphaC5a. In alphaC5aR-treated mice, serum levels of IL-6 and TNF-alpha and bacterial counts in various organs were significantly reduced during CLP when compared with control CLP animals. These studies demonstrate for the first time that C5aR is upregulated in lung, liver, kidney, and heart during the early phases of sepsis and that blockade of C5aR is highly protective from the lethal outcome of sepsis.

Correlates of antibiotic-resistant group B streptococcus isolated from pregnant women.

Despite antibiotic prophylaxis for at-risk mothers during labor and delivery, group B streptococcus still causes substantial morbidity and mortality among newborns. Resistance to antibiotics recommended for penicillin-allergic pregnant women, such as erythromycin and clindamycin, has increased. A better understanding of factors associated with group B streptococcus resistance is essential to effectively prevent group B streptococcus disease.A total of 117 sequential group B streptococcus isolates were obtained between August 1999 and March 2000 from pregnant women at the University of Michigan Medical Center. Serotype and susceptibility to ten antimicrobials using disk diffusion with E-test for confirmation were determined, and the association between several host factors and colonization with a resistant strain was evaluated. Group B streptococcus was frequently resistant to erythromycin (29%) and clindamycin (21%) but was susceptible to all other antimicrobials tested. A stepwise logistic regression model revealed that black ethnicity (P =.02) and carriage of a serotype V strain (P =.01) were associated with group B streptococcus resistance. Among this population of pregnant women, black ethnicity and serotype V were the strongest predictors of colonization with an erythromycin- or clindamycin-resistant group B streptococcus strain. A better understanding of factors associated with antibiotic resistance is needed to minimize group B streptococcus disease risks and to maximize effective chemoprophylaxis.

Candida transmission and sexual behaviors as risks for a repeat episode of Candida vulvovaginitis.

OBJECTIVE: To assess associations between female and male factors and the risk of recurring Candida vulvovaginitis. METHODS: A prospective cohort study of 148 women with Candida vulvovaginitis and 78 of their male sexual partners was conducted at two primary care practices in the Ann Arbor, Michigan, area. RESULTS: Thirty-three of 148 women developed at least one further episode of Candida albicans vulvovaginitis within 1 year of follow-up. Cultures of Candida species from various sites of the woman (tongue, feces, vulva, and vagina) and from her partner (tongue, feces, urine, and semen) did not predict recurrences. Female factors associated with recurrence included recent masturbating with saliva (hazard ratio 2.66 [95% CI 1.17-6.06]) or cunnilingus (hazard ratio 2.94 [95% CI 1.12-7.68]) and ingestion of two or more servings of bread per day (p

Genomic analysis of penicillin-resistant Streptococcus pneumoniae in Southeastern Michigan.

OBJECTIVE: The emergence of multidrug resistance within Streptococcus pneumoniae population was analysed, correlating penicillin resistance Pen(R) with secondary antibiotic resistance, capsular serotype, and genetic diversity among isolates. METHODS: DNA fingerprinting, following macro-restriction enzyme digestion and pulse field gel electrophoresis (PFGE), and restriction fragment analysis of the PBP 2b gene, following PCR amplification, were performed on the Pen(R) S. pneumoniae, among 377 clinical isolates obtained from the clinical microbiology laboratory (University of Michigan Medical Center). RESULTS: Overall 35% of the isolates were Pen(R) of which 45% demonstrated high-level penicillin (Pen(R)-R, MIC>1). Respiratory isolates were more likely to be Pen(R) (p <0.001) than non-respiratory isolates and the rate of Pen(R)-R was significantly increased in children <10 years of age (59.6%, p <0.02). Secondary antibiotic resistance was more frequently associated with Pen(R)-R. Genomic DNA fingerprinting analysis and restriction fragment analysis of the PBP 2b gene demonstrated genomic divergence with discrete conserved pattern in the PBP 2b gene among the resistant isolates. CONCLUSION: The emergence of multidrug resistance in the S. pneumoniae population in SE Michigan is not due to expansion of a single or limited number of resistant clones, is occurring most frequently in the paediatric population and is associated with a decreased susceptibility to penicillin.

Clinical correlation of the CLSI susceptibility breakpoint for piperacillin- tazobactam against extended-spectrum-beta-lactamase-producing Escherichia coli and Klebsiella species.

We assessed infections caused by extended-spectrum-beta-lactamase-producing Escherichia coli or Klebsiella spp. treated with piperacillin-tazobactam to determine if the susceptibility breakpoint predicts outcome. Treatment was successful in 10 of 11 nonurinary infections from susceptible strains and in 2 of 6 infections with MICs of >16/4 mug/ml. All six urinary infections responded to treatment regardless of susceptibility.

The effectiveness of standard povidone iodine surgical preparation in decontaminating external fixator components.

The purpose of this study was to evaluate the effectiveness of standard iodine surgical scrubs to remove bacteria from external fixator components. Sterile adjustable external fixation clamps, Schanz pins, and carbon fibre rods were coated with a sterile protein solution and immersed in solution of coagulase negative Staphylococcus (10(3)organisms/ml). They were then decontaminated in standard fashion using a povidone iodine scrub and paint solution. After neutralisation the components were sonicated, serially diluted, plated on blood agar, and incubated for 24h. Unassembled external fixation components were examined individually, and as assembled pin-rod-clamp constructs with and without manipulation of the clamp. Of the three external fixation components (pins, rods, clamps) the highest number of bacterial colony forming units was seen on the external fixation clamps. Manipulation of the assembled construct significantly increased the mean bacterial colony counts compared to the assembled non-manipulated construct (p=0.0007). Standard surgical preparation does not remove all bacteria from external fixators during subsequent operative procedures.