A meta-analysis of metronidazole and vancomycin for the treatment of Clostridium difficile infection, stratified by disease severity

The aim of this meta-analysis was to compare the efficacy of metronidazole and vancomycin for the treatment of Clostridium difficile infection, especially to investigate which agent was superior for treating either mild or severe C. difficile infection. A meta-analysis of randomized controlled trials and cohort studies identified in Pubmed, Embase, and the Cochrane Library was conducted. Four randomized controlled trials and two cohort studies involving 1218 patients were included in this meta-analysis. Metronidazole was inferior to vancomycin for treating C. difficile infection in terms of both initial clinical cure rates (risk ratio, RR = 0.91, 95% confidence interval, CI = 0.84–0.98, p = 0.02) and sustained cure rates (RR = 0.88, 95% CI = 0.82–0.96, p = 0.003). For mild C. difficile infection, the efficacy of metronidazole and vancomycin resulted in similar clinical cure rates (RR = 0.94, 95% CI = 0.84–1.04, p = 0.21) and sustained cure rates (RR = 0.93, 95% CI = 0.83–1.05, p = 0.26). For severe C. difficile infection the efficacy of vancomycin was superior to metronidazole in terms of clinical cure rates (RR = 0.81, 95% CI = 0.69–0.95, p = 0.009), whereas sustained cure rates were similar (RR = 0.86, 95% CI = 0.72–1.02, p = 0.08). Regarding microbiological cure metronidazole therapy was as effective as vancomycin therapy (RR = 0.88, 95% CI = 0.64–1.21, p = 0.43). Recurrence rates with metronidazole and vancomycin for both mild C. difficile infection (RR = 0.95, 95% CI = 0.56–1.60, p = 0.85) and severe C. difficile infection (RR = 1.27, 95% CI = 0.85–1.91, p = 0.25) were not different. Likewise, no difference in all-cause mortality was found as well (RR = 0.87, 95% CI = 0.56–1.35, p = 0.53). In conclusion, vancomycin provides improved initial clinical and sustained cure rates in patients with C. difficile infection compared with metronidazole, especially in patients with severe C. difficile infection. In view of these data, vancomycin may be considered first line therapy for severe C. difficile infection.