Metronidazole susceptibility in Clostridium difficile isolates recovered from cases of C-difficile-associated disease treatment failures and successes

Despite high clinical efficacy, a small number of patients with Clostridium difficile-associated disease (CDAD) do not respond to treatment with metronidazole. We looked for evidence of metronidazole resistance in human C. difficile isolates from 632 patients with CDAD treated with metronidazole, 14(2%) of whom failed treatment. C. difficile isolates were available from 10 of the metronidazole-failure cases and were matched with isolates from 20 contemporary control CDAD patients who responded to treatment with metronidazole. The mean (+/-SD) MIC of metronidazole-failure-associated C, difficile isolates was similar to the mean (+/-SD) MIC of isolates from metronidazole-success cases (E-test; 0.23+/-0.21 vs 0.29+/-0.19 mu g/mL, P = 0.4). Restriction endonuclease analysis typing revealed that no particular C. difficile strain was associated with metronidazole treatment failure. Clinical CDAD treatment failures with metronidazole could not be attributed to decreased susceptibility of the causative C. difficle isolate to metronidazole. (C) 1999 Academic Press.