Pathways through which water, sanitation, hygiene, and nutrition interventions reduce antibiotic use in young children: a mediation analysis of a cluster-randomized trial.

Background: Low-cost, household-level water, sanitation, and hygiene (WASH) and nutrition interventions can reduce pediatric antibiotic use, but the mechanism through which interventions reduce antibiotic use has not been investigated.
Methods: We conducted a causal mediation analysis using data from the WASH Benefits Bangladesh cluster-randomized trial (NCT01590095). Among a subsample of children within the WSH, nutrition, nutrition+WSH, and controls arms (N=1,409), we recorded caregiver-reported antibiotic use at ages 14 and 28 months and collected stool at age 14 months. Mediators included caregiver-reported child diarrhea, acute respiratory infection (ARI), and fever; and enteric pathogen carriage in stool measured by qPCR. Models controlled for mediator-outcome confounders.
Findings: The receipt of any WSH or nutrition intervention reduced antibiotic use in the past month by 5.5 percentage points (95% CI 1.2, 9.9) through all pathways, from 49.5% (95% CI 45.9%, 53.0%) in the control group to 45.0 % (95% CI 42.7%, 47.2%) in the pooled intervention group. Interventions reduced antibiotic use by 0.6 percentage points (95% CI 0.1, 1.3) through reduced diarrhea, 0.7 percentage points (95% CI 0.1, 1.5) through reduced ARI with fever, and 1.8 percentage points (95% CI 0.5, 3.5) through reduced prevalence of enteric viruses. Interventions reduced antibiotic use through any mediator by 2.5 percentage points (95% CI 0.2, 5.3).
Interpretation: Our findings bolster a causal interpretation that WASH and nutrition interventions reduced pediatric antibiotic use through reduced infections in a rural, low-income population.
Funding: Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases.