Clinicians who treat patients with Clostridium difficile-associated diarrhea (CDAD) in Quebec, Canada, have noted an apparent increase in the proportion of patients who experience relapse. To determine whether there was an increase in the frequency of treatment failure and of recurrence of CDAD after treatment, we reviewed data on cases that had been diagnosed in a hospital in the province of Quebec during the period 1991-2004. The frequency of recurrences within 60 days after the initial diagnosis was measured using Kaplan-Meier analysis, and Cox regression was used for multivariate analysis. Among patients who had initially been treated with metronidazole, the proportion whose regimens were switched to vancomycin or for whom vancomycin was added because of a disappointing response did not vary between 1991 and 2002 (66 [9.6%] of 688 patients overall) but more than doubled in 2003-2004 (112 [25.7%] of 435; P < .001). Among 845 patients treated with metronidazole only, the 60-day probability of recurrence increased dramatically in 2003-2004 (47.2%), compared with 1991-2002 (20.8%; P < .001). During 1991-2002, the probabilities of recurrence were 20.0%, 13.8%, and 28.9% among individuals aged 0-17, 18-64, and > or = 65 years, respectively; during 2003-2004, the probabilities were 25.0%, 27.1%, and 58.4%, respectively. In 2003-2004, there was an increase in the proportion of patients with CDAD believed, by their attending physicians, to have experienced metronidazole treatment failure, as well as an increase in the frequency of post-metronidazole therapy recurrences, especially among elderly persons.
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