Comparative effectiveness of Clostridium difficile treatments: a systematic review

Ann Intern Med. 2011 Dec 20;155(12):839-47. doi: 10.7326/0003-4819-155-12-201112200-00007.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review
  • Systematic Review

MeSH terms

  • Aminoglycosides / therapeutic use
  • Anti-Bacterial Agents / therapeutic use*
  • Clostridium Infections / drug therapy*
  • Clostridium Infections / microbiology
  • Clostridium Infections / mortality
  • Clostridium difficile*
  • Comparative Effectiveness Research
  • Diarrhea / drug therapy
  • Diarrhea / microbiology
  • Drug Therapy, Combination
  • Fidaxomicin
  • Humans
  • Metronidazole / therapeutic use
  • Recurrence
  • Vancomycin / therapeutic use

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • Metronidazole
  • Vancomycin
  • Fidaxomicin