Sustained Clinical Response as an Endpoint in Treatment Trials of Clostridium difficile-Associated Diarrhea

Recurrence of diarrhea following initially successful treatmentis a major shortcoming in the treatment of Clostridium diffi-cile-associated diarrhea (CDAD). Sustained response is a clinical endpoint proposed to account for differences among treatment agents with respect to a combination of initial response/cure and recurrence. Until recently, vancomycin was the only FDA-approved treat-ment for C. difficile infection (CDI). Treatment guidelines have recommended metronidazole for a first occurrence of nonsevere CDI and for a first relapse or reinfection (2, 3, 4). Vancomycin and metronidazole are both effective in providing initial response, with85 % cure rates, but 20 to 40 % of patients whose symptoms resolve have recurrent disease caused by relapse of the original infection or reinfection from external sources (2, 3, 4). In parallel with changes in strain prevalence and severity of disease, clinical response rates have changed with metronidazole during the last