JAC Advance Access originally published online on August 7, 2008
Journal of Antimicrobial Chemotherapy 2008 62(5):1046-1052; doi:10.1093/jac/dkn313
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Original research |
Emergence of reduced susceptibility to metronidazole in Clostridium difficile
1 Department of Microbiology, Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK 2 Department of Microbiology, Old Medical School, The General Infirmary, Leeds LS1 3EX, UK 3 Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands 4 Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy
Received 23 May 2008; returned 29 June 2008; revised 8 July 2008; accepted 9 July 2008
* Correspondence address. Department of Microbiology, Old Medical School, The General Infirmary, Leeds LS1 3EX, UK. Tel: +44-113-3926818; Fax: +44-113-3435649; E-mail: mark.wilcox{at}leedsth.nhs.uk
Objectives: Antimicrobial treatment for Clostridium difficile infection (CDI) has typically been metronidazole, although reports have questioned the efficacy of this option. We screened recently isolated C. difficile (2005–06) for susceptibility to metronidazole and compared results for historic isolates (1995–2001).
Methods: C. difficile ribotypes 001 (n = 86), 106 (n = 81) and 027 (n = 48) and isolates from the 10 other most prevalent ribotypes in Leeds (n = 57) were screened using spiral gradient endpoint analysis (SGE). C. difficile with metronidazole SGE MICs 
6 mg/L were analysed further by agar incorporation and Etest. Multiple-locus variable-number tandem-repeat analysis (MLVA) typing was performed for 28 C. difficile isolates.
Results: No reduced metronidazole susceptibility was observed in C. difficile ribotypes 106 and 027 (geometric mean SGE MICs 1.11 and 0.90 mg/L, respectively). In contrast, 21 (24.4%) C. difficile ribotype 001 demonstrated reduced susceptibility to metronidazole (geometric mean SGE MICs 3.51 mg/L, P < 0.001). Variations in susceptibility were observed relating to the method and media, but increased metronidazole MICs were confirmed by an agar incorporation method. Geometric mean agar incorporation MICs for historic C. difficile ribotype 001 (n = 72) were 1.03 (range 0.25–2) mg/L compared with 5.94 (4–8) mg/L (P < 0.001) for recent isolates displaying reduced metronidazole susceptibility. MLVA typing revealed two clonal complexes of C. difficile with reduced susceptibility to metronidazole.
Conclusions: We have demonstrated the emergence of reduced susceptibility to metronidazole in 24.4% of the recent C. difficile ribotype 001 isolates from our institution. Our observations could have implications in the clinical setting due to the poor penetration of metronidazole into the colon.
Keywords: antibiotics , diarrhoea , pseudomembranous colitis
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