RANDOMIZED PLACEBO-CONTROLLED TRIAL OF SACCHAROMYCES-BOULARDII IN COMBINATION WITH STANDARD ANTIBIOTICS FOR CLOSTRIDIUM-DIFFICILE DISEASE

Objective.-To determine the safety and efficacy of a new combination treatment for patients with Clostridium difficile-associated disease (CDD). The treatment combines the yeast Saccharomyces boulardii with an antibiotic (vancomycin hydrochloride or metronidazole). Design.-A double-blind, randomized, placebo-controlled, parallel-group intervention study in patients with active CDD. Patients received standard antibiotics and S boulardii or placebo for 4 weeks, and were followed up for an additional 4 weeks after therapy. Effectiveness was determined by comparing the recurrence of CDD in the two groups using multivariate analysis to control for other risk factors for CDD. Setting.-National referral study of ambulatory or hospitalized patients from three main study coordinating centers. Patients.-A total of 124 eligible consenting adult patients, including 64 who were enrolled with an initial episode of CDD, and 60 who had a history of at least one prior CDD episode. Patients who were immunosuppressed due to acquired immunodeficiency syndrome or cancer chemotherapy within 3 months were not eligible. Intervention.-Treatment with oral S boulardii (1 g/d for 4 weeks) or placebo in combination with a standard antibiotic. Main Outcome Measure.-Recurrence of active CDD. Results.-A history of CDD episodes dramatically increased the likelihood of further recurrences. Multivariate analysis revealed that patients treated with S boulardii and standard antibiotics had a significantly lower relative risk (RR) of CDD recurrence (RR, 0.43; 95% confidence interval, 0.20 to 0.97) compared with placebo and standard antibiotics. The efficacy of S boulardii was significant (recurrence rate 34.6%, compared with 64.7% on placebo; P=.04) in patients with recurrent CDD, but not in patients with initial CDD (recurrence rate 19.3% compared with 24.2% on placebo; P=.86). There were no serious adverse reactions associated with S boulardii. Conclusions.-The combination of standard antibiotics and S boulardii was shown to be an effective and safe therapy for these patients with recurrent CDD; no benefit of S boulardii was demonstrated for those with an initial episode of CDD.