title: Comparative effectiveness of Clostridium difficile treatments: a systematic review.
abstract: BACKGROUND
  Clostridium difficile infection is increasing in incidence and severity. The optimal treatment is unknown.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  MEDLINE, AMED, ClinicalTrials.gov, and Cochrane databases (search dates: inception through August 2011, limited to English-language reports); bibliography review.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  No antimicrobial agent is clearly superior for the initial cure of C. difficile infection. Recurrence is less frequent with fidaxomicin than with vancomycin.
  
  
  BACKGROUND
  U.S. Department of Health and Human Services.
authors.affiliation: Minneapolis Veterans Affairs Health Care System, University of Minnesota Medical School, Minnesota Evidence-based Practice Center, Minneapolis, Minnesota 55417, USA. drek0002@umn.edu
authors.forename: Dimitri M
authors.initials: DM
authors.lastname: Drekonja
authors.forename: Mary
authors.initials: M
authors.lastname: Butler
authors.forename: Roderick
authors.initials: R
authors.lastname: MacDonald
authors.forename: Donna
authors.initials: D
authors.lastname: Bliss
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Filice
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Rector
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Wilt
mesh_terms: D000617:Aminoglycosides / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016360:Clostridioides difficile; D003015:Clostridium Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D057186:Comparative Effectiveness Research; D003967:Diarrhea / Q000188:drug therapy / Q000382:microbiology; D004359:Drug Therapy, Combination; D000077732:Fidaxomicin; D006801:Humans; D008795:Metronidazole / Q000627:therapeutic use; D012008:Recurrence; D014640:Vancomycin / Q000627:therapeutic use
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D008795:Metronidazole; D014640:Vancomycin; D000077732:Fidaxomicin