Vancomycin superior to metronidazole for severe C. difficile diarrhea [Classics Series]

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1. Metronidazole and vancomycin had similar efficacy in treating mild cases of Clostridium difficile-associated diarrhea (CDAD).

2. Vancomycin was superior to metronidazole in treating severe cases of CDAD.

Original Date of Publication: August 1, 2007

Study Rundown: Clostridium difficile is a leading cause of antibiotic associated diarrhea and nosocomial infection. This study was the first randomized, controlled trial of metronidazole versus vancomycin treatment for C. difficile-associated diarrhea (CDAD) that stratified cases according to disease severity. No significant difference in efficacy was found in treating mild disease but vancomycin was superior to metronidazole in treating severe cases of CDAD. The findings are significant to treatment guidelines, as vancomycin is a more expensive drug and its use comes with the risk of selecting for vancomycin-resistant enterococci. Strengths of the study include its large sample size and the study design to reduce bias. In sum, severe cases of CDAD may require treatment with vancomycin rather than metronidazole, given the higher cure rates demonstrated with vancomycin therapy.

Please click to read study in CID

In-Depth [randomized, controlled study]: Published in Clinical Infectious Diseases in 2007, this was the first randomized, controlled study to compare vancomycin and metronidazole treatment of C. difficile-associated diarrhea based on disease severity. Patients were classified as having severe disease if they had endoscopic evidence of pseudomembranous colitis, were treated in the intensive care unit or had two or more of the following characteristics: 1) age >60 years, 2) temperature >38.3ᴼC, 3) albumin level <2.5 mg/dL, or 4) peripheral WBC count >15,000 cells/mm3 within 48 hours of study entry. The investigators assessed cure as resolution of diarrhea by day 6 of treatment and negative result of C. difficile-toxin A at days 6 and 10 of treatment. In mild cases of disease, metronidazole treatment resulted in cure in 90% of patients and vancomycin treatment resulted in cure in 98% of patients (p = 0.36). In severe cases of disease, metronidazole cured 76% of patients while vancomycin cured 97% of patients (p = 0.02).

By Adrienne Cheung, Andrew Cheung, M.D.

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