Effectiveness of Bio-K plus for the prevention of Clostridioides difficile infection: Stepped-wedge cluster-randomized controlled trial

Objective: To evaluate the impact of administering probiotics to prevent Clostridioides difficile infection (CDI) among patients receiving therapeutic antibiotics.Design: Stepped-wedge cluster-randomized trial between September 1, 2016, and August 31, 2019.Setting: This study was conducted in 4 acute-care hospitals across an integrated health region.Patients: Hospitalized patients, aged >= 55 years.Methods: Patients were given 2 probiotic capsules daily (Bio-K+, Laval, Quebec, Canada), containing 50 billion colony-forming units of Lactobacillus acidophilus CL1285, L. casei LBC80R, and L. rhamnosus CLR2. We measured hospital-acquired CDI (HA-CDI) and the number of positive C. difficile tests per 10,000 patient days as well as adherence to administration of Bio-K+ within 48 and 72 hours of antibiotic administration. Mixed-effects generalized linear models, adjusted for influenza admissions and facility characteristics, were used to evaluate the impact of the intervention on outcomes.Results: Overall adherence of Bio-K+ administration ranged from 76.9% to 84.6% when stratified by facility and periods. Rates of adherence to administration within 48 and 72 hours of antibiotic treatment were 60.2% -71.4% and 66.7%-75.8%, respectively. In the adjusted analysis, there was no change in HA-CDI (incidence rate ratio [IRR], 0.92; 95% confidence interval [CI], 0.68-1.23) or C. difficile positivity rate (IRR, 1.05; 95% CI, 0.89-1.24). Discharged patients may not have received a complete course of Bio-K+. Our hospitals had a low baseline incidence of HA-CDI. Patients who did not receive Bio-K+ may have differential risks of acquiring CDI, introducing selection bias.Conclusions: Hospitals considering probiotics as a primary prevention strategy should consider the baseline incidence of HA-CDI in their population and timing of probiotics relative to the start of antimicrobial administration.