JAC Advance Access originally published online on October 8, 2006
Journal of Antimicrobial Chemotherapy 2006 58(5):1062-1065; doi:10.1093/jac/dkl364
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Tigecycline does not induce proliferation or cytotoxin production by 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 2 June 2006; returned 12 July 2006; revised 9 August 2006; accepted 14 August 2006
*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: Data on the risk of Clostridium difficile infection (CDI) associated with specific antibiotics are difficult to obtain because of confounding clinical factors. It is particularly important to evaluate the propensity of new antibiotics to induce CDI. We have examined the propensity of tigecycline to induce CDI using a human gut model.
Methods: We used a three-stage chemostat human gut model to study the effects of tigecycline on indigenous gut microflora and C. difficile. Two epidemic C. difficile were studied in separate experiments: PCR ribotype 001 (UK, CD001) and PCR ribotype 027 (North America, CD027). Tigecycline MICs for 39 C. difficile representing 19 distinct PCR ribotypes were also determined.
Results: Tigecycline MICs were 0.06 mg/L for all the C. difficile strains. Peak tigecycline concentrations in the gut model were 10.9 and 11.7 mg/L in CD027 and CD001 experiments, respectively. Tigecycline instillation invoked marked decreases in numbers of bacteroides and bifidobacteria (107–108 cfu/mL) and lesser reductions in facultative anaerobes. Despite markedly altered gut microflora, CD001 and CD027 remained as spores for the duration of the experiment, with no evidence of proliferation or cytotoxin production.
Conclusions: Tigecycline exposure did not induce C. difficile proliferation or cytotoxin production despite reduced competing microflora. The potency of tigecycline against C. difficile may contribute to the low risk of CDI induction. Factors other than gut microflora colonization resistance may be important in preventing C. difficile spore germination, proliferation and cytotoxin production.
Keywords: colonization resistance , ribotype 001 , ribotype 027
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