Comparison of clinical and microbiological response to treatment of Clostridium difficile associated disease with metronidazole and vancomycin

Background. There have been recent reports of frequent treatment failure associated with the use of metronidazole for treatment of Clostridium difficile-associated disease. We tested the hypothesis that treatment failure with metronidazole is associated with a suboptimal microbiological response in comparison with that of vancomycin. Methods. We conducted a 9-month prospective observational study of patients with C. difficile-associated disease. Cox proportional hazards models were used to compare metronidazole-treated and vancomycin-treated patients in terms of time to resolution of diarrhea and time to reduction of C. difficile in stool to an undetectable level. Results. Of 52 study patients with C. difficile-associated disease, 34 (65%) received initial therapy with oral metronidazole, and 18 (35%) received initial therapy with oral vancomycin. Diarrhea resolved in 190% of patients who completed 10 days of treatment with either agent. However, vancomycin-treated patients were more likely to develop undetectable levels of C. difficile (adjusted hazard ratio, 3.99; 95% confidence interval, 1.41-11.3; P = .009) and to have resolution of diarrhea (adjusted hazard ratio, 4.17; 95% confidence interval, 1.53-11.40; P =. 005) during the first 5 days of therapy. Ten metronidazole-treated patients (29%) had their treatment changed to oral vancomycin because of persistent symptoms. Seven (70%) of these 10 patients had < 1 log reduction in C. difficile concentration; however, only 4 had completed >= 6 days of metronidazole treatment at the time of the treatment change. Conclusion. In an observational study with a limited number of subjects, a majority of patients with C. difficile associated disease responded to therapy with metronidazole or vancomycin. Failure with metronidazole treatment may be attributable to a slower and less consistent microbiological response than that with oral vancomycin treatment.