Treatment Strategies for Recurrent Clostridium difficile Infection.

BACKGROUND Recurrent Clostridium difficile infection represents a major clinical challenge. Treatment is often based on empiric selection from relatively few options supported by limited clinical evidence. OBJECTIVE To review and evaluate the literature on therapeutic alternatives for recurrent C. difficile infection. DATA SOURCES The MEDLINE, PubMed, Embase, and Cochrane databases were searched from inception to 2013 for published evidence in English on the treatment of recurrent C. difficile infection. The search terms were "Clostridium difficile", "recurrent" or "relapse", and "treatment". STUDY SELECTION AND DATA EXTRACTION Studies of any design were eligible for inclusion. Two reviewers assessed abstracts, full articles, and reference lists from retrieved articles and clinical practice guidelines to identify relevant literature. DATA SYNTHESIS The evidence to guide treatment of recurrent C. difficile infection is limited, with 24 studies meeting the inclusion criteria for this review. A repeat course of oral metronidazole or vancomycin is recommended for treatment of mild to moderate first recurrences and has not been found to influence the likelihood of subsequent recurrence. Oral vancomycin may be preferred for more severe infections; however, the severity score warrants further study and validation. For the treatment of second and subsequent recurrences, tapered or pulsed vancomycin regimens have been recommended in practice guidelines, despite very limited clinical evidence. Similarly, the potential benefits of longer treatment courses of oral vancomycin for second and subsequent recurrences warrant investigation. The potential role, including costs and benefits, of new agents such as fidaxomicin in the treatment of recurrent C. difficile infection remains to be determined. Although there is insufficient evidence to recommend probiotics as an adjunct to conventional treatment for recurrent infection, there may be benefit in terms of prevention. CONCLUSIONS This literature review identified significant limitations in currently recommended interventions for the treatment of recurrent C. difficile infection. It has also provided insight into the available evidence for determining the appropriateness of therapy for patients with recurrent infection.