Effectiveness of Bio-K+ 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.

Adequacy of empirical antifungal therapy and effect on outcome among patients with invasive Candida species infections.

OBJECTIVES: Although inadequate antimicrobial therapy has been demonstrated in multiple studies to increase the risk for death in bacterial infections, few data investigating the effect of antifungal therapy on outcome of serious fungal disease are available. We sought to assess the adequacy of empirical therapy and its effect on mortality in invasive Candida species infections. METHODS: Population-based surveillance of all patients with Candida spp. cultured from blood and/or cerebrospinal fluid was conducted. Adequacy of empirical therapy was assessed according to published guidelines. RESULTS: During a 5 year period, 207 patients had an invasive Candida spp. infection identified; in 199 cases (96%) adequate data were available for assessment of treatment and outcome at hospital discharge. One hundred and three (52%) cases were due to Candida albicans, 44 (22%) were due to Candida glabrata and the remainder were due to other species. Between the time of culture draw and reporting of a positive culture, only 64 (32%) patients were treated with empirical therapy; this was deemed adequate in 51 (26%). Patients who received adequate empirical therapy had a significant decrease in crude mortality [14/51 (27%) versus 68/148 (46%); risk ratio 0.60 (95% confidence interval 0.37-0.96); P = 0.02]. After adjusting for age and the need for intensive care unit admission in logistic regression analysis, the use of adequate empirical therapy was independently associated with a reduced risk for death [odds ratio 0.46 (95% confidence interval 0.22-1.00); P = 0.05]. CONCLUSIONS: Adequate empirical therapy is used in a minority of patients with invasive Candida spp. infections but is associated with improved survival.