Increasing Risk of Relapse after Treatment of Clostridium difficile Colitis in Quebec, Canada

Abstract

Background.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. Methods.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.Results.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;).Among 845 patients treated with metronidazole only, the 60-day probability of recurrence P !.001increased dramatically in 2003-2004 (47.2%), compared with 1991-2002 (20.8%; ).During 1991-2002, P !.001 the probabilities of recurrence were 20.0%, 13.8%, and 28.9% among individuals aged 0-17, 18-64, and у65 years, respectively; during 2003-2004, the probabilities were 25.0%, 27.1%, and 58.4%, respectively. Conclusion.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.Clostridium difficile was identified as the etiological agent of pseudomembranous colitis in 1978 [1].Early studies claimed that metronidazole was as effective as oral vancomycin for therapy [2,3], and the former became the standard first-line treatment for this common cause of nosocomial infectious diarrhea.After recommendations were made by the Centers for Disease Control and Prevention to avoid the use of vancomycin in the hope of slowing down the emergence of vancomycin-resistant pathogens [4], metronidazole started to be administered to the overwhelming majority of patients with C. difficile-associated diarrhea (CDAD).Unfortunately, 5%-35% of patients experience a recurrence of CDAD, regardless of whether metronida-