OBJECTIVES: A network meta-analysis (NMA) was conducted to compare the efficacy of fidaxomicin (FDX) with vancomycin (VCM) and metronidazole (MTZ) for the treatment of Clostridium difficile infection (CDI).

METHODS: MEDLINE, Embase, Cochrane CENTRAL and ICHUSHI were searched systematically up to September 12, 2016, for randomized controlled trials (RCT) of adult patients with CDI. Recent clinical study reports were also provided by the study sponsor. Endpoints included in the NMA were clinical cure rate during treatment, recurrence rate during follow-up period and sustained cure rate (defined as clinical cure without recurrence during study period). Patient subgroups of interest were those with non-severe CDI, an initial episode of CDI, age ≥ 65 years and concomitant antibiotics during CDI treatment. A Bayesian framework was used and all outcomes were estimated using fixed-effect models.

RESULTS: The search identified three RCTs that compared FDX with VCM, and five that compared VCM with MTZ. FDX was significantly more effective than VCM in reducing recurrence rate (odds ratio [OR]: 0.50; 95% credible intervals [CrIs]: 0.37, 0.68) and in sustained cure rate (1.61 [1.27, 2.05]), while FDX was more effective than MTZ in all outcomes (1.77 [1.11, 2.83] for clinical cure, 0.44 [0.27, 0.72] for recurrence and 2.39 [1.63, 3.47] for sustained cure) in the total population. In all subgroups, FDX was more effective than both VCM and MTZ for recurrence and sustained cure but not for recurrence in patients on concomitant antibiotics (vs MTZ). Furthermore, FDX was more effective than MTZ for sustained cure in the non-severe CDI and concomitant antibiotic subgroups.

CONCLUSIONS: FDX was more effective than both VCM and MTZ for recurrence rate and sustained cure rate in the total population and in most patient subgroups.