Restoration of vancomycin susceptibility in Enterococcus faecalis by antiresistance determinant gene transfer.

We assessed the ability of gene transfer to reverse vancomycin resistance in class A (VanA) glycopeptide-resistant Enterococcus faecalis. Recombinant shuttle vectors containing a vanH promoter-vanA antisense gene cassette fully restored vancomycin susceptibility through a combined transcriptional activator binding domain decoy and inducible vanA antisense RNA effect.

SME-type carbapenem-hydrolyzing class A beta-lactamases from geographically diverse Serratia marcescens strains.

Three sets of carbapenem-resistant Serratia marcescens isolates have been identified in the United States: 1 isolate in Minnesota in 1985 (before approval of carbapenems for clinical use), 5 isolates in Los Angeles (University of California at Los Angeles [UCLA]) in 1992, and 19 isolates in Boston from 1994 to 1999. All isolates tested produced two beta-lactamases, an AmpC-type enzyme with pI values of 8.6 to 9.0 and one with a pI value of approximately 9.5. The enzyme with the higher pI in each strain hydrolyzed carbapenems and was not inhibited by EDTA, similar to the chromosomal class A SME-1 beta-lactamase isolated from the 1982 London strain S. marcescens S6. The genes encoding the carbapenem-hydrolyzing enzymes were cloned in Escherichia coli and sequenced. The enzyme from the Minnesota isolate had an amino acid sequence identical to that of SME-1. The isolates from Boston and UCLA produced SME-2, an enzyme with a single amino acid change relative to SME-1, a substitution from valine to glutamine at position 207. Purified SME enzymes from the U. S. isolates had beta-lactam hydrolysis profiles similar to that of the London SME-1 enzyme. Pulsed-field gel electrophoresis analysis revealed that the isolates showed some similarity but differed by at least three genetic events. In conclusion, a family of rare class A carbapenem-hydrolyzing beta-lactamases first described in London has now been identified in S. marcescens isolates across the United States.

Activities of taurolidine in vitro and in experimental enterococcal endocarditis.

In vitro, the antimicrobial agent taurolidine inhibited virtually all of the bacteria tested, including vancomycin-resistant enterococci, oxacillin-resistant staphylococci, and Stenotrophomonas maltophilia, at concentrations between 250 and 2,000 microg/ml. Taurolidine was not effective in experimental endocarditis. While it appears unlikely that this antimicrobial would be useful for systemic therapy, its bactericidal activity and the resistance rates found (<10(-9)) are favorable indicators for its possible development for topical use.

Meta-analysis of antibiotic prophylaxis in endoscopic retrograde cholangiopancreatography (ERCP).

BACKGROUND AND STUDY AIMS: Considerable controversy exists regarding the role of antibiotic prophylaxis prior to endoscopic retrograde cholangiopancreatography (ERCP), in that various studies of antibiotic prophylaxis have reached conflicting conclusions. The aim of this meta-analysis is to synthesize the data in order to determine whether antibiotic prophylaxis reduces the rate of occurrence of bacteremia and/or the rate of sepsis/cholangitis among patients undergoing ERCP. PATIENTS AND METHODS: Clinical trials were selected via Medline and Pubmed using subject words and textwords "ERCP", "antibiotic" and "antibiotic prophylaxis". Summary estimates of the risk ratios for the outcomes of bacteremia and sepsis/cholangitis were calculated. RESULTS: After 49 abstracts had been reviewed, seven randomized placebo-controlled trials of antibiotic prophylaxis prior to ERCP were identified. Upon further review, two studies were excluded because patients received antibiotics before and after the ERCP. Four studies reported on the clinical outcome of bacteremia. Five studies reported on the clinical outcome of sepsis/cholangitis. The summary relative risk of the association between antibiotic prophylaxis and bacteremia was 0.39 (95% CI, 0.12-1.29). For sepsis/cholangitis the summary relative risk was 0.91 (95 % CI, 0.39-2.15). CONCLUSIONS: Antibiotic prophylaxis prior to ERCP may reduce the incidence of bacteremia but this has little clinical relevance. Prophylaxis does not substantially reduce the incidence of sepsis/cholangitis and thus the routine use of antibiotic prophylaxis cannot be recommended.

Epidemiology and clinical outcomes of patients with multiresistant Pseudomonas aeruginosa.

We conducted a case-series study of multiresistant Pseudomonas aeruginosa in patients who did not have cystic fibrosis. Patient characteristics, antibiotic exposures, time course of emergence of resistance, and clinical outcomes were examined. Twenty-two patients were identified from whom P. aeruginosa resistant to ciprofloxacin, imipenem, ceftazidime, and piperacillin was isolated. Nineteen (86%) had clinical infection. Patients received prolonged courses of antipseudomonal antibiotics before isolation of multiresistant P. aeruginosa. Nine of 11 patients with soft-tissue infection exhibited resolution of clinical infection but usually required surgical removal of infected tissue with or without revascularization. Overall, three patients died. In two instances in which multiple isolates with different susceptibility profiles from the same patient were available, pulsed-field gel electrophoresis profiles of serial isolates were indistinguishable or closely related. This study illustrates that multiresistant P. aeruginosa emerges in a stepwise manner after exposure to antipseudomonal antibiotics and results in adverse outcomes.