Metronidazole Resistance in Clostridium difficile

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Abstract
Sir—Jang et al. [1] reported high-level resistance to metronidazole in Clostridium difficile isolates obtained from horses. To determine whether metronidazole resistance was of clinical importance in human patients with C. difficile-associated diarrhea (CDAD), we analyzed clinical C. difficile isolates obtained from patients with CDAD who failed to respond to metronidazole treatment [2]. Prospective surveillance at one VA Medical Center over a 10-year period documented only 14 (2%) treatment failures among 632 episodes of CDAD treated with metronidazole [3]. We tested the susceptibility of all 10 available C. difficile isolates from the metronidazole treatment failures and 20 C. difficile isolates from contemporary control CDAD cases (CDAD cases successfully treated with metronidazole) using E-test and agar dilution methods. The MIC (mean ± SD) of metronidazole failure-associated C. difficile isolates was similar to the MIC (mean ± SD) of isolates from metronidazole success cases (E-test; 0.23±0.21 vs. 0.29±0.19 µg/ml; P = 0.4) [2]. All isolates had an MIC < 1 µg/mL by E-test and by agar dilution; therefore, we concluded that treatment failures could not be attributed to decreased susceptibility of the infecting C. difficile strain to metronidazole.