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Bowel colonization with resistant gram-negative bacilli after antimicrobial therapy of intra-abdominal infections: observations from two randomized comparative clinical trials of ertapenem therapy

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Abstract

The selection of resistant gram-negative bacilli by broad-spectrum antibiotic use is a major issue in infection control. The aim of this comparative study was to assess the impact of different antimicrobial regimens commonly used to treat intra-abdominal infections on the susceptibility patterns of gram-negative bowel flora after completion of therapy. In two international randomized open-label trials with laboratory blinding, adults with complicated intra-abdominal infection requiring surgery received piperacillin-tazobactam (OASIS 1) or ceftriaxone/metronidazole (OASIS II) versus ertapenem for 4–14 days. Rectal swabs were obtained at baseline, end of therapy, and 2 weeks post-therapy. Escherichia coli and Klebsiella spp. were tested for production of extended-spectrum β-lactamase (ESBL). Enterobacteriaceae resistant to the agent used were recovered from 19 of 156 (12.2%) piperacillin-tazobactam recipients at the end of therapy compared to 1 (0.6%) patient at baseline (p<0.001) in OASIS I, and from 33 of 193 (17.1%) ceftriaxone/metronidazole recipients at the end of therapy compared to 5 (2.6%) patients at baseline (p<0.001) in OASIS II. Ertapenem-resistant Enterobacteriaceae were recovered from 1 of 155 and 1 of 196 ertapenem recipients at the end of therapy versus 0 and 1 ertapenem recipients at baseline in OASIS I and II, respectively. Resistant Enterobacteriaceae emerged significantly less often during treatment with ertapenem than with the comparator in both OASIS I (p<0.001) and OASIS II (p<0.001). The prevalence of ESBL-producers increased significantly during therapy in OASIS II among 193 ceftriaxone/metronidazole recipients (from 4 [2.1%] to 18 [9.3%]) (p<0.001), whereas no ertapenem recipient was colonized with an ESBL-producer at the end of therapy in either study. Selection for imipenem-resistant Pseudomonas aeruginosa was uncommon in all treatment groups. In these studies, the frequency of bowel colonization with resistant Enterobacteriaceae substantially increased in patients treated with either piperacillin-tazobactam or ceftriaxone/metronidazole, but not in patients treated with ertapenem.

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Authors and Affiliations

  1. Merck & Co., Whitehouse Station, NJ, USA

    M. J. DiNubile, I. Friedland, C. Y. Chan, M. R. Motyl, H. Giezek & M. Shivaprakash

  2. Merck Research Laboratories, PO Box 4, BL3-4, West Point, PA, 19486, USA

    M. J. DiNubile

  3. Stroger (Cook County) Hospital, Chicago Infectious Disease Research Institute and Rush University School of Medicine, Chicago, IL, USA

    R. A. Weinstein & J. P. Quinn

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  1. M. J. DiNubile
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  2. I. Friedland
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  3. C. Y. Chan
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  4. M. R. Motyl
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  6. M. Shivaprakash
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Correspondence to M. J. DiNubile.

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DiNubile, M.J., Friedland, I., Chan, C.Y. 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 24, 443–449 (2005). https://doi.org/10.1007/s10096-005-1356-0

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