Comparative Effectiveness of Clostridium Difficile Treatments: a Systematic Review

Background: Clostridium difficile infection is increasing in incidence and severity. The optimal treatment is unknown.

Purpose: To 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 Sources: MEDLINE, AMED, ClinicalTrials.gov, and Cochrane databases (search dates: inception through August 2011, limited to English-language reports); bibliography review.

Study Selection: Randomized, 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 Extraction: Study 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 Synthesis: 11 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.

Limitations: Definitions 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.

Conclusion: No antimicrobial agent is clearly superior for the initial cure of C. difficile infection. Recurrence is less frequent with fidaxomicin than with vancomycin.

Primary Funding Source: U.S. Department of Health and Human Services.