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Clin Infect Dis. 2006 Sep 1;43(5):547-52. Epub 2006 Jul 25.

Prospective, randomized inpatient study of oral metronidazole versus oral metronidazole and rifampin for treatment of primary episode of Clostridium difficile-associated diarrhea.

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Department of Medicine, McMaster University, Hamilton, Ontario, Canada.



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.


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.


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).


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.

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