Simon D Baines1, Jane Freeman, Mark H Wilcox. 1. Department of Microbiology, University of Leeds and The General Infirmary, Old Medical School, Leeds LS1 3EX, UK.
Abstract
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/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.
OBJECTIVES:Clostridium difficileinfection (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.
Authors: Brian T Fisher; Julia Shaklee Sammons; Yimei Li; Peter de Blank; Alix E Seif; Yuan-Shung Huang; Marko Kavcic; Sarah Klieger; Tracey Harris; Kari Torp; Douglas Rheam; Ami Shah; Richard Aplenc Journal: J Pediatric Infect Dis Soc Date: 2014-02-16 Impact factor: 3.164
Authors: Hannah C Harris; Emma L Best; Charmaine Normington; Nathalie Saint-Lu; Frédérique Sablier-Gallis; Jean de Gunzburg; Antoine Andremont; Mark H Wilcox; Caroline H Chilton Journal: Antimicrob Agents Chemother Date: 2020-12-16 Impact factor: 5.191
Authors: Sarah Underwood; Shuang Guan; Vinod Vijayasubhash; Simon D Baines; Luke Graham; Richard J Lewis; Mark H Wilcox; Keith Stephenson Journal: J Bacteriol Date: 2009-09-25 Impact factor: 3.490
Authors: Katie Saxton; Simon D Baines; Jane Freeman; Rachael O'Connor; Mark H Wilcox Journal: Antimicrob Agents Chemother Date: 2008-08-18 Impact factor: 5.191