title: Prospective, randomized inpatient study of oral metronidazole versus oral metronidazole and rifampin for treatment of primary episode of Clostridium difficile-associated diarrhea.
abstract: BACKGROUND
  To date, no randomized trial to address the use of adjunctive rifampin in addition to metronidazole for the treatment of Clostridium difficile-associated diarrhea has been reported. Rifampin has excellent in vitro activity against C. difficile and penetrates into cellular materials where the organisms may persist.
  
  
  METHODS
  This was a prospective, randomized, single-blinded study of 39 patients that compared therapy with metronidazole alone versus therapy with metronidazole and rifampin for 10 days to treat laboratory-confirmed primary episode C. difficile-associated diarrhea. Twenty patients were randomly assigned to the metronidazole group, and 19 were randomly assigned to the metronidazole and rifampin group. Data were analyzed by intention-to-treat analysis using the 2-tailed Kaplan-Meier method and the log-rank test.
  
  
  RESULTS
  Adjunctive rifampin treatment for 10 days, compared with treatment with metronidazole alone for 10 days, was associated with a similar median time to symptom improvement (9.0 days vs. 6.5 days; P=.74), a similar median time to first relapse (26 days vs. 16 days; P=.23), a similar proportion of patients with relapse by study day 40 (42% vs. 38%; P=1.0), and a similar proportion of patients experiencing nonfatal adverse events (37% vs. 40%; P=.55). There were a significantly higher number of deaths in the metronidazole and rifampin group, compared with the metronidazole group (6 of 19 patients vs. 1 of 20 patients; P=.04), but there were fewer laboratory-confirmed relapses by study day 40 (2 vs. 4; P=.66).
  
  
  CONCLUSIONS
  We conclude that there is no role for routine rifampin as an adjunct to treatment with metronidazole for hospitalized patients with C. difficile-associated diarrhea. The cure rates for both treatment groups remain unacceptably low, and better treatments are urgently needed.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Danny
authors.initials: D
authors.lastname: Lagrotteria
authors.forename: Serena
authors.initials: S
authors.lastname: Holmes
authors.forename: Marek
authors.initials: M
authors.lastname: Smieja
authors.forename: Fiona
authors.initials: F
authors.lastname: Smaill
authors.forename: Christine
authors.initials: C
authors.lastname: Lee
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003967:Diarrhea / Q000188:drug therapy*; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage* / Q000627:therapeutic use*; D012293:Rifampin / Q000008:administration & dosage* / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D008795:Metronidazole; D012293:Rifampin