Probiotics for the prevention of antibiotic-associated adverse events in children - a systematic review to inform development of a core outcome set

Abstract

IntroductionRoutine use of probiotics during antibiotic therapy in children remains a subject of discussion. To facilitate synthesis of individual study results and guideline formulation, it is important to assess predefined, similar, and clinically important outcomes. Core outcome sets are a proposed solution for this issue. Aim of this review was to document choice, design, and heterogeneity of outcomes in studies that assessed the effects of probiotics used for the prevention of antibiotic-associated adverse events in children. MethodsA systematic literature search covering three major databases was performed. Trials that evaluated oral probiotics use concomitant with antibiotic therapy in children were included. Data on outcome definitions, measurement instruments, and follow-up were extracted. The outcomes were assigned to predefined core areas and domains. Data were analyzed descriptively. ResultsThirty-six trials were included in this review. Diarrhea, the most commonly reported outcome, had diagnostic criteria clearly defined only in 20 trials. In total, sixteen different definitions of diarrhea were identified. Diarrhea duration, severity and etiology were reported in 8, 4 and 6 studies, respectively. Nineteen studies assessed gastrointestinal symptoms other than diarrhea. Seven studies reported outcomes related to resource use or the economic impact of the intervention. Only 2 studies assessed outcomes related to life impact. None of the studies predefined adverse events of probiotic use. ConclusionsIdentified outcomes were characterized by substantial heterogeneity. Majority of outcomes were not designed to evaluate endpoints of real-life relevance. Results from this review suggest the need for a new core outcome set consisting of outcomes important for decision-making.