Background . During an epidemic of Clostridium difficile-associated disease (CDAD) caused by a strain that is a hyper-producer of toxins A and B, the frequency of a first recurrence after metronidazole treatment of the initial episode doubled in 2003–2004, compared with 1991–2002.

Methods . To examine whether administration of metronidazole as treatment for a first recurrence of CDAD remained appropriate, we reviewed data for patients with CDAD diagnosed in a hospital in Quebec, Canada, during 1991–2005, who experienced a first recurrence. The frequency of a second recurrence within 60 days after the first one was measured using Kaplan-Meier analysis. Cox regression was used for multivariate analysis.

Results . A total of 463 patients had a first recurrence of CDAD, of whom 154 (33.3%) experienced a second recurrence. Independent predictors of a second recurrence were age and duration of hospitalization after the first recurrence; this latter finding suggested that many such episodes were reinfections rather than relapses. Neither choice of treatment drug (metronidazole or vancomycin) nor use of the same drug for treatment of first recurrence, as had been used during the initial episode, was associated with increased risk of a second recurrence. However, 51 patients (11.0%) developed at least 1 complication (i.e., shock, need for colectomy, megacolon, perforation, or death within 30 days) during the first recurrence. Older age, a high leukocyte count, and renal failure at first recurrence were strongly associated with a complicated CDAD.

Conclusions . Metronidazole is not inferior to vancomycin for treatment of patients with a first recurrence of CDAD, but the risk of complications with any treatment of CDAD may be higher than has previously been documented.