JAC Advance Access originally published online on September 4, 2008
Journal of Antimicrobial Chemotherapy 2008 62(5):1078-1085; doi:10.1093/jac/dkn358
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Original research |
Comparison of oritavancin versus vancomycin as treatments for clindamycin-induced Clostridium difficile PCR ribotype 027 infection 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, Leeds Teaching Hospitals NHS Trust, The General Infirmary, Old Medical School, Leeds, Leeds LS1 3EX, UK
Received 1 July 2008; returned 21 July 2008; revised 5 August 2008; accepted 6 August 2008
* Correspondence address. 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: To compare the efficacy of oritavancin and vancomycin in the treatment of Clostridium difficile infection (CDI) using an in vitro human gut model.
Methods: We induced CDI by instilling clindamycin into an in vitro gut model primed with pooled human faeces and C. difficile ribotype 027 spores. Oritavancin and vancomycin were instilled in separate experiments at levels equivalent to those expected in the faeces (vancomycin) of patients or levels limited by the solubility of the drug (oritavancin).
Results: Clindamycin exposure elicited C. difficile proliferation and high-level cytotoxin production in both experiments. Vancomycin instillation reduced vegetative C. difficile numbers within 1 day but did not affect the numbers of C. difficile spores. Oritavancin instillation markedly reduced C. difficile vegetative numbers and spores to below the limits of detection within 2 days. Cytotoxin titres in both experiments declined to the limits of detection after instillation with oritavancin or vancomycin, but did so more quickly (within 5 days) in the vancomycin experiment. Cessation of vancomycin instillation was associated with further C. difficile proliferation and high-level cytotoxin production. Conversely, toxin recrudescence was not observed following cessation of oritavancin.
Conclusions: Both oritavancin and vancomycin were effective in treating clindamycin-induced CDI in a human gut model, but only oritavancin appeared active against spore forms of C. difficile. Furthermore, recurrence of high-level cytotoxin production was observed following vancomycin instillation but not oritavancin. Oritavancin therapy may be more effective in treating CDI than vancomycin, possibly because it may prevent recrudescence of C. difficile spores.
Keywords: spores , chemostat , faeces
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