Treatment failure and recurrence of Clostridium difficile infection following treatment with vancomycin or metronidazole: a systematic review of the evidence.

The objective of this review was to evaluate the frequency of treatment failure and recurrence of Clostridium difficile infection (CDI) following treatment with vancomycin or metronidazole in recently performed studies (last 10 years). Searches in PubMed and Scopus were performed by two reviewers independently. Data regarding treatment failure and recurrence following metronidazole and vancomycin treatment were extracted and analysed. In total, 39 articles (7005 patients) were selected for inclusion in the systematic review. The reported treatment failure was 22.4% with metronidazole (16 studies) and 14.2% with vancomycin (8 studies). Recurrence of CDI occurred in 27.1% of patients following metronidazole treatment (18 studies) and 24.0% of patients following vancomycin treatment (8 studies). Mean treatment failure and recurrence in the selected studies was 22.3% (24 studies) and 22.1% (37 studies). The reported outcomes depended on the study design (higher in prospective and retrospective cohort studies than in randomised controlled trials), geographic location of the study (higher in North America than in Europe and Asia), funding (higher in studies funded by non-profit organisations than pharmaceutical companies), mean age of the studied population (higher in older patients) and duration of follow-up (higher in studies with follow-up >1 month). In conclusion, infection with C. difficile is associated with 22.4% and 14.2% treatment failure and 27.1% and 24.0% recurrence after treatment with metronidazole and vancomycin, respectively. The variation in the reported outcomes amongst studies depends on the study design, location, funding, age and follow-up period.