Antibiotic exposure and ‘response failure’ for subsequent respiratory tract infections: an observational cohort study of UK preschool children in primary care

Background Childhood antibiotic exposure has important clinically relevant implications. These include disruption to the microbiome, antibiotic resistance, and clinical workload manifesting as treatment ‘failure’. Aim To examine the relationship between the number of antibiotic courses prescribed to preschool children for acute respiratory tract infections (RTI), in the preceding year, and subsequent RTIs that failed to respond to antibiotic treatment (‘response failures’). Design and setting A cohort study using UK primary care data from the Clinical Practice Research Datalink, 2009 to 2016. Method Children aged 12 to 60 months (1 to 5 years) who were prescribed an antibiotic for an acute RTI (upper and lower RTI or otitis media) were included. One random index antibiotic course for RTI per child was selected. Exposure was the number of antibiotic prescriptions for acute RTI up to 12 months before the index antibiotic prescription. The outcome was ‘response failure’ up to 14 days after index antibiotic prescription, defined as: subsequent antibiotic prescription; referral; hospital admission; death; or emergency department attendance within 3 days. The authors used logistic regression models to estimate the odds between antibiotic exposure and response failure. Results Out of 114 329 children who were prescribed an antibiotic course for acute RTI, children who received ≥2 antibiotic courses for acute RTIs in the preceding year had greater odds of response failure; one antibiotic course: adjusted odds ratio (OR) 1.03 (95% confidence interval [CI] = 0.88 to 1.21), P = 0.67, n = 230 children; ≥2 antibiotic courses: adjusted OR 1.32 (CI = 1.04 to 1.66), P = 0.02, n = 97. Conclusion Childhood antibiotic exposure for acute RTI may be a good predictor for subsequent response failure (but not necessarily because of antibiotic treatment failure). Further research is needed to improve understanding of the mechanisms underlying response failure.