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Article
June 22, 1994

A Randomized Placebo-Controlled Trial of Saccharomyces boulardii in Combination With Standard Antibiotics for Clostridium difficile Disease

Author Affiliations

From the Department of Medicinal Chemistry, School of Pharmacy (Drs McFarland and Elmer), and the Division of Gastroenterology, Department of Medicine, School of Medicine (Dr Surawicz and Mss Moyer and Melcher), University of Washington, Seattle; Biocodex Inc, Seattle (Dr McFarland); the Division of Infectious Diseases, Department of Medicine, University of Kentucky, and Lexington Veterans Affairs Medical Center, Lexington, Ky (Dr Greenberg and Mss Bowen and Cox); the Division of Infectious Diseases, Department of Internal Disease, University of Michigan, Ann Arbor (Drs Fekety, Noorani, and Harrington); and the Department of Medicine, Columbia University College of Physicians & Surgeons, New York, NY (Drs Rubin and Greenwald).

JAMA. 1994;271(24):1913-1918. doi:10.1001/jama.1994.03510480037031
Abstract

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.(JAMA. 1994;271:1913-1918)

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