JAC Advance Access published online on December 26, 2008
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkn502
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Original research |
Activity of vancomycin against epidemic Clostridium difficile strains in a human gut model
1 Department of Microbiology, Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK 2 Department of Microbiology, The General Infirmary, Old Medical School, Leeds LS1 3EX, UK
Received 18 September 2008; returned 22 October 2008; revised 12 November 2008; accepted 18 November 2008
* Corresponding author. Department of Microbiology, The General Infirmary, Old Medical School, Leeds LS1 3EX, UK. Tel: +44 113-3926818; Fax: +44 113-3435649; E-mail: mark.wilcox{at}leedsth.nhs.uk
Objectives: Vancomycin and metronidazole remain the only primary options for the treatment of Clostridium difficile infection (CDI). Recent reports have suggested a superior clinical response to vancomycin therapy compared with metronidazole, but this has been difficult to prove or explain. There are few robust in vitro data of the effects of antibiotic treatment of CDI in a gut reflective setting.
Methods: We used clindamycin to induce high-level toxin production by two epidemic C. difficile PCR ribotypes in a human gut model of CDI. Vancomycin was instilled into the models to achieve in vivo faecal concentrations. C. difficile populations and toxin titres, and gut bacterial populations and vancomycin levels were monitored before, during and after vancomycin instillation.
Results: Clindamycin treatment elicited C. difficile germination and high-level cytotoxin production. Vancomycin reduced total viable counts and cytotoxin titres of both C. difficile PCR ribotypes, with no evidence of recurrence before the model runs were ended. C. difficile PCR ribotype 027 populations exhibited greater germination capacity than did PCR ribotype 106. Vancomycin was more rapidly effective against the greater numbers of PCR ribotype 027 vegetative forms. Vancomycin showed no activity against C. difficile spores.
Conclusions: Bacteriological response to vancomycin varies between strains causing CDI, possibly correlating with the extent of germination capacity. Vancomycin effectively reduced vegetative forms and cytotoxin titres of both of the epidemic C. difficile PCR ribotypes evaluated, but showed no anti-spore activity. Comparison with the results of a previous gut model study showed that vancomycin was more effective than metronidazole in reducing C. difficile PCR ribotype 027 numbers and cytotoxin titres.
Key Words: PCR ribotype 027 , toxin , colitis