Adjunctive use of Saccharomyces boulardii versus bismuth subsalicylate in the management of non-Clostridioides difficile nosocomial diarrhea in severely ill patients: a three-arm randomized controlled trial

Abstract

Background: Although nosocomial diarrhea other than Clostridioides difficile infection (CDI) is common, only limited evidence on antidiarrheal medications has been studied. Probiotics, known for preventing antibiotic-associated diarrhea (AAD) by restoring microbiota and bismuth subsalicylate (BSS), a traditional medication with anti-microbial and anti-secretory effects are interested to be used. We then conducted randomized controlled trial (RCT) to evaluate the use of Saccharomyces boulardii (S. boulardii) versus BSS as an adjunctive treatment for nosocomial diarrhea. Methods: This is a prospective RCT conducted at Department of Medicine, Siriraj Hospital, Bangkok, Thailand. Patients with new onset nosocomial diarrhea and negative C. difficile toxin in stool were randomly allocated to receive 5 days of either S. boulardii (Sb group) or BSS (BSS group), compared to standard care (SC group). Treatment outcomes including stool weight, frequency and consistency were compared between groups. Results: Seventy-two eligible patients were recruited from August 2016 to February 2018. Demographic data in these three groups were comparable. The median changes of stool weight from baseline to day 5 of treatment between the groups were not significantly different (Sb 68 vs. BSS 170 vs. SC 156 g, P=0.11). Median change of stool frequency (Sb 0.9 vs. BSS 1.0 vs. SC 1.6 times/day, P=0.14) and consistency were similar (Sb 0.2 vs. BSS 0.4 vs. SC 0.2, P=0.95). No adverse event was reported. Conclusions: Our study revealed that S. boulardii and BSS added no benefit in treatment of non-CDI nosocomial diarrhea. These were applicable across all outcomes including weight, frequency and consistency of stool. More studies are needed to ascertain a better treatment for nosocomial diarrhea.