Journal Article

Effects of piperacillin/tazobactam on <i>Clostridium difficile</i> growth and toxin production in a human gut model

Simon D. Baines, Jane Freeman and Mark H. Wilcox

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 55, issue 6, pages 974-982
Published in print June 2005 | ISSN: 0305-7453
Published online April 2005 | e-ISSN: 1460-2091 | DOI:
Effects of piperacillin/tazobactam on Clostridium difficile growth and toxin production in a human gut model

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Objectives: Clostridium difficile infection (CDI) is a major cause of morbidity in the nosocomial environment. Antimicrobial agents such as the third-generation cephalosporins, lincosamides and aminopenicillins are well known for their propensity to induce CDI, but the definitive reasons why remain to be elucidated. Despite their broad spectrum of activity against both aerobic and anaerobic bacteria, the ureidopenicillins remain a class of antimicrobials infrequently associated with the development of CDI.

Methods: We used a triple-stage chemostat model that simulates the human gut to study the effects of the ureidopenicillin/β-lactamase inhibitor combination piperacillin/tazobactam on gut bacterial populations and C. difficile.

Results: Piperacillin/tazobactam rapidly reduced all enumerated gut bacterial populations (including bacteroides, bifidobacteria and lactobacilli) below the limits of detection by the end of the piperacillin/tazobactam instillation period. Despite such widespread disruption of gut bacterial populations, C. difficile populations remained principally as spores, with no sustained proliferation or high-level cytotoxin production observed.

Conclusions: Factors other than reduced colonization resistance must be responsible for determining whether CDI develops following antimicrobial administration. We believe the gut model is a promising approach for the study of C. difficile pathogenesis reflecting in vivo events likely to occur in CDI.

Keywords: colonization resistance; pathogenesis; germination; spores

Journal Article.  5267 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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