The Effect of Antibiotic Therapy for Intraabdominal Infections on Selection of Antibiotic-Resistant Bowel Flora
Abstract & Commentary
By Stan Deresinski, MD, FACP, Clinical Professor of Medicine, Stanford; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor for Infectious Disease Alert.
Synopsis: Relative to treatment with either ceftriaxone plus metronidazole or with piperacillin/tazobactam, ertapenem administration is least likely to select for resistant bacterial flora in the gastrointestinal tract.
Sources: Dinubile MJ, et al. Bowel Colonization with Resistant Gram-Negative Bacilli After Antimicrobial Therapy of Intra-Abdominal Infections: Observations From Two Randomized Comparative Clinical Trials of Ertapenem Therapy. Eur J Clin Microbiol Infect Dis. 2005;24:443-449; DiNubile MJ, et al. Acquisition of Resistant Bowel Flora During a Double-Blind Randomized Clinical Trial of Ertapenem Versus Piperacillin-Tazobactam for Intraabdominal Infections. Antimicrob Agents Chemother. 2005;49:3217-3221.
Several randomized, comparative trials have demonstrated the efficacy of ertapenem in the treatment of patients with intraabdominal infections. In the course of those trials, each of which demonstrated no significant difference between treatment regimens, fecal samples were collected and DiNubile and colleagues have now examined the effect of the individual treatment regimens on the emergence of antibiotic resistant aerobic Gram negative bacilli.
Two of the trials compared ertapenem to piperacillin/tazobactam (P/T). The proportion of P/T recipients from whom P/T-resistant Enterobacteriaceae was recovered increased from 0.6% at baseline to 12.2% at the end of therapy (EOT). In the second trial examining these same 2 treatment regimens, this proportion increased from 0.8% to 7.8%. Meanwhile, the frequency of recovery of ertapenem-resistant Enterobacteriaceae from ertapenem recipients changed from 0.6% to 0% in OASIS I and from 0.8% to 1.6% in the second trial.
In OASIS II, ertapenem was compared to ceftriaxone plus metronidazole (C/M). Once again, there was no significant recovery of antibiotic-resistant Gram negatives among ertapenem recipients. In contrast, among C/M recipients, the frequency of recovery of ceftriaxone-resistant Enterobacteriaciae increased from 2.6% at baseline to 17.1% at EOT and to 22.4% two weeks later. In addition, ESBL-producing Enterobacteriaceae were recovered from 2.1% of ceftriaxone recipients at baseline, 9.3% at EOT, and 17.2% at 2 weeks post-therapy.
Of particular note is that there was no significant increase in recovery of imipenem-resistant Pseudomonas aeruginosa among ertapenem recipients in any of the 3 trials.
Commentary
The gastrointestinal tract serves as an enormous potential reservoir of resistant bacteria. Whatever the indication, the administration of antimicrobials may have a profound effect on that flora, including the selection of antibiotic resistant bacteria. These organisms may subsequently cause infection in the affected individual, as well as serving as a source for environmental contamination and spread to other patients. As a consequence, one of the important factors that should be taken into account in the selection of antibiotic therapy is its effect on the bacterial ecology of the patient and the environment.
These analyses provide a clear distinction among 3 antibiotic regimens in their likelihood of selection of fecal antibiotic-resistant Enterobacteriaceae. They demonstrate that ertapenem posed no significant risk for the selection of these resistant bacteria, that C/M therapy served as a strong selector of resistance, including ESBL-producing Enterobacteriaceae, and that P/T therapy was intermediate in its effects.
One concern that has been raised regarding the use of ertapenem is that of the potential for selection of resistance to other carbapenems in Pseudomonas aeruginosa. However, no significant increase in imipenem-resistant P. aeruginosa was identified in any of the trials in patients who were treated with ertapenem. In addition, no significant increase in carbapenem resistance among P. aeruginosa or Enterobacteriaceae was identified 19 months after the introduction to the antibiotic formulary at the Ohio State University Medical Center.1
Reference
- Goff DA, Mangino J. Ertapenem Effect on Gram-Negative Pathogens 19 Months After Formulary Addition. 45th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, D.C., December 16-19, 2005, Abstract K-1511.
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