Efficacy of Rifaximin Versus Metronidazole for Treatment of Clostridium difficile Infection

Purpose: Infection with Clostridium difficile results in symptoms of frequent diarrhea and abdominal pain and can lead to serious complications. There is an increase in C difficile infection and an emergence of a more virulent strain of C difficile in local communities and hospitals. Standard treatment for C difficile includes a 10- to 14-day course of oral metronidazole or oral vancomycin; however, relapses may occur in up to 20% of treated patients. Although metronidazole is not currently approved by the Food and Drug Administration for treatment of C difficile, it is the more common first-line therapy. Metronidazole is associated with potential adverse effects and is absorbed in the intestines, suggesting that it has limited direct effect in the colon. Rifaximin is a nonabsorbed, oral antibiotic with minimal systemic absorption (<0.4%) and broad-spectrum activity against intestinal pathogens, including C difficile, and could be an effective alternative therapy. This single-blind, randomized, single-center, outpatient study compared the efficacy and safety of rifaximin with metronidazole for treatment of newly acquired C difficile infection. Methods: This study included patients with diarrhea who tested positive for a C difficile stool toxin A/B assay during the screening phase (days −3 to 0). Patients were randomized to receive rifaximin (400 mg three times daily) or metronidazole (500 mg three times daily) for 14 days. During the follow-up phase (days 14 to 44), patients completed stool diary cards and were monitored weekly by telephone. Stool toxin was assessed at days 0 and 44. Results: Of the 16 patients (10 females, 6 males) who received treatment, 4 withdrew (2 each from the rifaximin and metronidazole groups): 3 for noncompliance and 1 due to continued diarrhea. The 12 remaining patients were evenly split between the rifaximin and metronidazole groups. At day 44, 6 patients from the rifaximin group (100%) and 5 patients from the metronidazole group (83%) tested negative for C difficile toxin. One patient from the metronidazole group tested positive at day 44 for C difficile toxin but was asymptomatic. Conclusion: Rifaximin 1200 mg/d administered for 14 days alleviated symptoms by eliminating C difficile infection with 100% efficacy in patients who completed the trial. Rifaximin was well tolerated, and its low absorption profile potentially decreases adverse effects associated with antibiotic treatment. Rifaximin may provide a therapeutic alternative to metronidazole for treatment of C difficile infection.