title: Saccharomyces boulardii to Prevent Antibiotic-Associated Diarrhea: A Randomized, Double-Masked, Placebo-Controlled Trial.
abstract: Background.  Antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) are common complications of antibiotic use. Data on the efficacy of probiotics to prevent AAD and CDAD are unclear. We aimed to evaluate the efficacy of Saccharomyces boulardii to prevent AAD and CDAD in hospitalized adult patients. Methods.  We conducted a multicenter, phase III, double-masked, randomized, placebo-controlled trial in hospitalized patients who received systemic antibiotic treatment in 15 hospitals in Germany between July 2010 and October 2012. Participants received Perenterol forte 250 mg capsules or matching placebo twice per day within 24 hours of initiating antibiotic treatment, continued treatment for 7 days after antibiotic discontinuation, and were then observed for 6 weeks. Results.  Two thousand four hundred forty-four patients were screened. The trial was stopped early for futility after inclusion of 477 participants. Two hundred forty-six patients aged 60.1 ± 16.5 years and 231 patients aged 56.5 ± 17.8 were randomized to the S boulardii group and the placebo group, respectively, with 21 and 19 AADs in the respective groups (P = .87). The hazard ratio of AAD in the S boulardii group compared with the placebo group was 1.02 (95% confidence interval, .55-1.90; P = .94). Clostridium difficile-associated diarrhea occurred in 0.8% of participants (4 of 477). Nine serious adverse events were recorded in the S boulardii group, and 3 serious adverse events were recorded in the placebo group. None were related to study participation. Conclusions.  We found no evidence for an effect of S boulardii in preventing AAD or CDAD in a population of hospitalized patients without particular risk factors apart from systemic antibiotic treatment. ClinicalTrials.gov Identifier.  NCT01143272.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Clinical Research Unit, Bernhard Nocht Institute for Tropical Medicine.
authors.forename: Stephan
authors.initials: S
authors.lastname: Ehrhardt
authors.affiliation: Department of Epidemiology , Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland.
authors.forename: Nan
authors.initials: N
authors.lastname: Guo
authors.affiliation: Department of Tropical Medicine at the Bernhard Nocht Institute , German Armed Forces Hospital of Hamburg.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hinz
authors.affiliation: Clinical Research Unit , Bernhard Nocht Institute for Tropical Medicine.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schoppen
authors.affiliation: Infectious Disease Epidemiology , Bernhard Nocht Institute for Tropical Medicine.
authors.forename: Jürgen
authors.initials: J
authors.lastname: May
authors.affiliation: Department of Medicine II , Klinikum Vest GmbH , Marl.
authors.forename: Markus
authors.initials: M
authors.lastname: Reiser
authors.affiliation: Department of Internal Medicine , Federal Armed Forces Hospital Ulm.
authors.forename: Maximilian Philipp
authors.initials: MP
authors.lastname: Schroeder
authors.affiliation: Department of Medicine I , University Medical Center Hamburg-Eppendorf.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schmiedel
authors.affiliation: Bethesda Krankenhaus Bergedorf, Klinik fur Innere Medizin.
authors.forename: Martin
authors.initials: M
authors.lastname: Keuchel
authors.affiliation: Department of Internal Medicine, Division for Tropical Medicine and Infectious Diseases , Rostock University Medical Center.
authors.forename: Emil C
authors.initials: EC
authors.lastname: Reisinger
authors.affiliation: Medical Clinic I , Hospital of Saarbrücken.
authors.forename: Andreas
authors.initials: A
authors.lastname: Langeheinecke
authors.affiliation: Department of Internal Medicine , Agaplesion Diakonieklinikum Hamburg.
authors.forename: Andreas
authors.initials: A
authors.lastname: de Weerth
authors.affiliation: I. Department of Internal Medicine, Johannes-Gutenberg-Universität Mainz, University Medical Centre; I. Department of Internal Medicine, Constance Hospital.
authors.forename: Marcus
authors.initials: M
authors.lastname: Schuchmann
authors.affiliation: Diakoniekrankenhaus Rotenburg (Wümme) GmbH, Zentrum für Pneumologie.
authors.forename: Tom
authors.initials: T
authors.lastname: Schaberg
authors.affiliation: Institute of Biostatistics and Clinical Research , University of Münster.
authors.forename: Sandra
authors.initials: S
authors.lastname: Ligges
authors.affiliation: Institute of Biostatistics and Clinical Research , University of Münster.
authors.forename: Maria
authors.initials: M
authors.lastname: Eveslage
authors.affiliation: Department of Tropical Medicine at the Bernhard Nocht Institute , German Armed Forces Hospital of Hamburg.
authors.forename: Ralf M
authors.initials: RM
authors.lastname: Hagen
authors.affiliation: Department of Medicine I, University Medical Center Hamburg-Eppendorf; Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Gerd D
authors.initials: GD
authors.lastname: Burchard
authors.affiliation: Department of Medicine I , University Medical Center Hamburg-Eppendorf.
authors.forename: Ansgar W
authors.initials: AW
authors.lastname: Lohse
keywords: Clostridium difficile-associated diarrhea; Saccharomyces boulardii; antibiotic-associated diarrhea; probiotic; randomized controlled trial