A Prospective Study of Risk Factors and Historical Trends in Metronidazole Failure for Clostridium difficile Infection

Background & Aims: Recent studies of Clostridium difficile infection (CDI) have indicated a dramatic increase in metronidazole failure. The aims of this study were to compare current and historical rates of metronidazole failure and to identify risk factors for metronidazole failure. Methods: Eighty-nine patients with CDI in 2004 to 2006 were followed for 60 days and were compared with a historical cohort of 63 CDI patients studied prospectively in 1998. Metronidazole failure was defined as persistent diarrhea after 10 days of therapy or a change of therapy to vancomycin. Stool samples were analyzed for the presence of the North American pulsed-field gel electrophoresis type-1 (NAP-1) strain. Results: Metronidazole failure rates were 35% in both cohorts. There was no difference in the median time to resolution of diarrhea (8 vs 5 d; P = .52) or the proportion with > 10 days of diarrhea (35% vs 29%; P = .51). Risk factors for metronidazole failure included recent cephalosporin use (odds ratio [OR], 32; 95% confidence interval [CI], 5-219), CDI on admission (OR, 23; 95% CI, 3-156), and transfer from another hospital (OR, 11; 95% CI, 2-72). The frequency of NAP-1 infection in patients with and without metronidazole failure was similar (26% vs 21%; P = .67). Conclusions: We found no difference in metronidazole failure rates in 1998 and 2004 to 2006. Patients with recent cephalosporin use, CDI on admission, and transfer from another hospital were more Likely to metronidazole failure. Infection with the epidemic NAP-1 strain was not associated with metronidazole failure in endemic CDI.