Effects of piperacillin/tazobactam on Clostridium difficile growth and toxin production in a human gut model.
OBJECTIVE
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/beta-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.
Baines
Simon D
SD
Department of Microbiology, University of Leeds and The General Infirmary, Old Medical School, Leeds LS1 3EX, UK.
Freeman
Jane
J
Wilcox
Mark H
MH
D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D016360:Clostridioides difficile / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D003603:Cytotoxins / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007422:Intestines / Q000382:microbiology*; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010878:Piperacillin / Q000008:administration & dosage*; D013171:Spores, Bacterial / Q000502:physiology; D000078142:Tazobactam
D000900:Anti-Bacterial Agents; D003603:Cytotoxins; D004791:Enzyme Inhibitors; D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin