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 t reatment for patients with Clostridium difficile-associated disease (C DD). The treatment combines the yeast Saccharomyces boulardii with an antibiotic (vancomycin hydrochloride or metronidazole). Design.-A doub le-blind, randomized, placebo-controlled, parallel-group intervention study in patients with active CDD. Patients received standard antibiot ics and S boulardii or placebo for 4 weeks, and were followed up for a n additional 4 weeks after therapy. Effectiveness was determined by co mparing the recurrence of CDD in the two groups using multivariate ana lysis to control for other risk factors for CDD. Setting.-National ref erral study of ambulatory or hospitalized patients from three main stu dy 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. P atients who were immunosuppressed due to acquired immunodeficiency syn drome or cancer chemotherapy within 3 months were not eligible. Interv ention.-Treatment with oral S boulardii (1 g/d for 4 weeks) or placebo in combination with a standard antibiotic. Main Outcome Measure.-Recu rrence 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 antibiot ics had a significantly lower relative risk (RR) of CDD recurrence (RR , 0.43; 95% confidence interval, 0.20 to 0.97) compared with placebo a nd standard antibiotics. The efficacy of S boulardii was significant ( recurrence rate 34.6%, compared with 64.7% on placebo; P=.04) in patie nts with recurrent CDD, but not in patients with initial CDD (recurren ce rate 19.3% compared with 24.2% on placebo; P=.86). There were no se rious 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 epis ode of CDD.