Continuation of antibiotics is associated with failure of metronidazole for Clostridium difficile-associated diarrhea

Background: Metronidazole is first-line therapy for C. difficile-associated diarrhea primarily because of its low cost relative to vancomycin. Currently, it is unknown which patients will fail metronidazole therapy. Our goal was to prospectively evaluate risk factors for metronidazole failure. Study: Included patients had symptomatic C. difficile-associated diarrhea, either mild or severe. Once enrolled, detailed baseline data were gathered. All interviews were performed daily while the patient was in the hospital for up to 14 days. If discharged prior to 14 days, the patient received a follow-up phone call on day 5 and day 14. Enrolled patients were given a daily stool survey to complete. Results: We enrolled 27 patients with C. difficile-associated diarrhea. All patients (10 of 10) who had their offending antibiotic(s) discontinued had symptomatic resolution of diarrhea by day 14 of metronidazole treatment. Conversely, 59% (10 of 17) of patients who remained on antibiotics during treatment had symptomatic resolution by day 14 (P = 0.02). The risk ratio for treatment failure was 2.0 (95% confidence interval, 1.29-3.10) in patients who remained on antibiotics. In our treatment group, there would be one additional metronidazole treatment success for every 2.4 patients who discontinued antibiotics. Conclusion: Patients who remain on antibiotics while undergoing treatment of C. difficile-associated diarrhea have a high likelihood of treatment failure with metronidazole.