A 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.
McFarland
L V
LV
Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle 98195.
Surawicz
C M
CM
Greenberg
R N
RN
Fekety
R
R
Elmer
G W
GW
Moyer
K A
KA
Melcher
S A
SA
Bowen
K E
KE
Cox
J L
JL
Noorani
Z
Z
D000328:Adult; D000368:Aged; D016360:Clostridioides difficile; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use*; D008875:Middle Aged; D012008:Recurrence; D014640:Vancomycin / Q000627:therapeutic use*; D015002:Yeast, Dried / Q000627:therapeutic use*
D008795:Metronidazole; D014640:Vancomycin