Emergence of reduced susceptibility to metronidazole in Clostridium difficile

Objectives: Antimicrobial treatment for Clostridium difficile infection (CDI) has typically been metro-nidazole, 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 (n5 86), 106 (n5 81) and 027 (n5 48) and isolates from the 10 other most prevalent ribotypes in Leeds (n5 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 ribo-type 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 incorpor-ation MICs for historic C. difficile ribotype 001 (n5 72) were 1.03 (range 0.25–2) mg/L compared wit