title: Acquisition of resistant bowel flora during a double-blind randomized clinical trial of ertapenem versus piperacillin-tazobactam therapy for intraabdominal infections.
abstract: Bowel colonization with resistant bacteria can develop in patients receiving broad-spectrum antimicrobial therapy. We compared the impact of two antimicrobial regimens often used to treat intraabdominal infections on susceptibility patterns of bowel flora at the end of therapy. In a double-blind clinical trial, adults with complicated intraabdominal infection requiring surgery were randomized to receive piperacillin-tazobactam (3.375 g every 6 h) or ertapenem (1 g once a day) for 4 to 14 days. Rectal swabs were obtained at baseline and at the end of study therapy to determine the acquisition rates of Enterobacteriaceae resistant to the study drug, extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli or Klebsiella species, Pseudomonas aeruginosa resistant to imipenem or piperacillin-tazobactam, and vancomycin-resistant Enterococcus faecalis or Enterococcus faecium. Treated patients were assessable for the acquisition of resistant bacteria if appropriate specimens were obtained at both time points. Enterobacteriaceae resistant to the treatment received were acquired during study therapy by 8/122 assessable piperacillin-tazobactam recipients (6.6%) compared to 0/122 assessable ertapenem recipients (P = 0.007). Neither ESBL-producing E. coli or Klebsiella species nor P. aeruginosa resistant to piperacillin-tazobactam was isolated from patients in either treatment group. Imipenem-resistant P. aeruginosa was acquired by two of the ertapenem recipients (1.6%) versus zero of the piperacillin-tazobactam recipients (P = 0.50). Vancomycin-resistant enterococci were acquired during therapy by 8/125 assessable ertapenem recipients (6.4%) versus 2/123 assessable piperacillin-tazobactam recipients (1.6%; P = 0.10). In this study, the acquisition of resistant Enterobacteriaceae occurred significantly more often in patients treated with piperacillin-tazobactam than in those treated with ertapenem.
authors.affiliation: Merck Research Laboratories, P.O. Box 4, BL3-4, West Point, PA 19486, USA. mark_dinubile@merck.com
authors.forename: Mark J
authors.initials: MJ
authors.lastname: DiNubile
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Chow
authors.forename: Vilas
authors.initials: V
authors.lastname: Satishchandran
authors.forename: Adam
authors.initials: A
authors.lastname: Polis
authors.forename: Mary R
authors.initials: MR
authors.lastname: Motyl
authors.forename: Murray A
authors.initials: MA
authors.lastname: Abramson
authors.forename: Hedy
authors.initials: H
authors.lastname: Teppler
mesh_terms: D018784:Abdominal Abscess / Q000382:microbiology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D004755:Enterobacteriaceae / Q000187:drug effects / Q000254:growth & development; D000077727:Ertapenem; D005260:Female; D006801:Humans; D007769:Lactams / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D010878:Piperacillin / Q000627:therapeutic use; D000077725:Piperacillin, Tazobactam Drug Combination; D012007:Rectum / Q000382:microbiology*; D016896:Treatment Outcome; D047090:beta-Lactams
chemical_list: D000900:Anti-Bacterial Agents; D007769:Lactams; D047090:beta-Lactams; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D000077727:Ertapenem; D010878:Piperacillin