Vancomycin Versus Metronidazole for Nonsevere Clostridioides difficile Infection: Are the Data Adequate to Change Practice?

Objective: To compare oral metronidazole and vancomycin for the treatment of mild-to-moderate Clostridioides difficile infection (mmCDI). Data Sources: A MEDLINE literature search (inception to November 2018) was performed using the search terms metronidazole, vancomycin, and Clostridium/Clostridioides difficile. Additional references were identified from a review of literature citations. Study Selection and Data Extraction: All English-language clinical studies (interventional and observational), meta-analyses, and cost-effectiveness analyses comparing the efficacy of metronidazole and vancomycin for mmCDI were evaluated. Data Synthesis: Nine clinical studies, 5 meta-analyses, and 1 cost-effectiveness analysis provided comparative data for metronidazole and vancomycin for the treatment of mmCDI. Improved treatment response with vancomycin as compared with metronidazole in adults with mmCDI reached statistical significance in a few studies; albeit, most studies and pooled analyses have results that numerically favor vancomycin. Furthermore, the cost per case treated appears to be lower with vancomycin compared with metronidazole based on data from hospitalized patients. Relevance to Patient Care and Clinical Practice: Recent updates to national guidelines now give preference to vancomycin over metronidazole for mmCDI; however, this has been a source of controversy. This review provides an appraisal of direct and indirect comparisons of oral metronidazole and vancomycin for mmCDI, including recent literature published after the release of current guidelines. Conclusions: The available outcome data suggesting that vancomycin is more effective than metronidazole, combined with the more favorable pharmacokinetics, safety, and tolerability profile of vancomycin, provide adequate clinical rationale for the preferential use of this agent for the treatment of mmCDI.