1 Center for Clinical Pharmaceutical Research, Chinese People’s Liberation Army General Hospital, Beijing, China;2 Department of Respiratory Diseases, Chinese People’s Liberation Army General Hospital, Beijing, PR China

Xiuzhen Di and Rui Wang contributed equally to this work.

Running Head: Metronidazole for Clostrdium difficile-associated diarrhea

The aim of this meta-analysis was to investigate the efficacy of metronidazole for treatment of Clostridium difficile associated diarrhea (CDAD). A meta-analysis of randomized controlled trials (RCTs) and cohort studies identified in Pubmed, Embase and the Cohrane Library was performed. Five RCTs and two cohort studies involving 1012 patients were included. Compared with therapy with antibiotic monotherapy regimens for CDAD patients, metronidazole was associated with similar clinical treatment success of vancomycin for mild CDAD patients(odds ratio, OR=0.59, 95% CI = 0.27 to 1.26, P=0.17), but metronidazole was inferior to vancomycin for severe CDAD patients (OR=0.17, 95% CI = 0.04 to 0.66, P=0.01). Metronidazole was as clinically effective as fusidic acid(OR=2.08 95% CI=0.74 to 5.82, P=0.16). No statistical differences in relapse rate were found between metronidazole and active comparators as a whole (OR=1.06, 95% CI=0.75 to 1.51, P=0.73), metronidazole and vancomycin(OR=1.02, 95% CI=0.65 to 1.62, P=0.82), metronidazole and fusidic acid (OR=0.77, 95% CI=0.38 to 1.55, P=0.43). Regarding all-cause mortality and drug related adverse effects (AEs), no differences were found between metronidazole and vancomycin (mortality, OR=1.54, 95% CI = 0.62 to 3.82, P=0.35), metronidazole and fusidic acid (AEs, OR=0.69, 95% CI = 0.09 to 5.11, P=0.72). In conclusion, patients tolerated all the drugs equally well and relapse rates were similar. The data suggest that metronidazole may be used as effectively as fusidic acid, and as vancomycin for mild CDAD patients, but is inferior to vancomycin for severe CDAD patients. Oral metronidazole is still widely used.