• Dimitri M Drekonja, Mary Butler, Roderick MacDonald, Donna Bliss, Gregory A Filice, Thomas S Rector, and Timothy J Wilt.
• Minneapolis Veterans Affairs Health Care System, University of Minnesota Medical School, Minnesota Evidence-based Practice Center, Minneapolis, Minnesota 55417, USA. drek0002@umn.edu
• Ann. Intern. Med. 2011 Dec 20; 155 (12): 839-47.

BackgroundClostridium difficile infection is increasing in incidence and severity. The optimal treatment is unknown.PurposeTo determine whether, among adults with C. difficile infection, treatment with certain antibiotics compared with others results in differences in initial cure, recurrence, and harms.Data SourcesMEDLINE, AMED, ClinicalTrials.gov, and Cochrane databases (search dates: inception through August 2011, limited to English-language reports); bibliography review.Study SelectionRandomized, controlled trials of adults with C. difficile infection, independent of outcomes, who were treated with medications available in the United States. Observational studies reporting strain were included.Data ExtractionStudy design, inclusion and exclusion criteria, quality and strength of evidence as assessed by 2 reviewers, study definitions, and duration of treatment and follow-up. Outcomes included initial cure, recurrence, and treatment harms.Data Synthesis11 trials that included 1463 participants were identified. Three trials compared metronidazole with vancomycin; 8 compared metronidazole or vancomycin with another agent, combined agents, or placebo. Strain was analyzed in 1 trial and 2 cohort studies. No study comparing 2 antimicrobial agents demonstrated a statistically significant difference for initial cure; all comparisons were of low to moderate strength of evidence. Moderate-strength evidence from 1 study demonstrated that recurrence was decreased with fidaxomicin versus vancomycin (15% vs. 25%; difference, -10 percentage points [95% CI, -17 to -3 percentage points]; P=0.005). Subgroup analysis of a single study comparing metronidazole with vancomycin for patients who have severe C. difficile infection showed no difference by intention-to-treat analysis; this was rated as insufficient-strength evidence. Harms, when reported, did not differ between treatments in any study.LimitationsDefinitions of diarrhea, C. difficile infection, initial cure, and relapse varied. Some studies reported insufficient detail to allow assessment of all randomly assigned participants or of harms.ConclusionNo antimicrobial agent is clearly superior for the initial cure of C. difficile infection. Recurrence is less frequent with fidaxomicin than with vancomycin.Primary Funding SourceU.S. Department of Health and Human Services.

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