AbstractBackgroundAntimicrobial resistance is a serious global health concern that emphasizes completing treatment course. Recently, the effectiveness of short versus longer antibiotic courses has been questioned. This study investigated the duration of prescribed antibiotics, their effectiveness, and associated risk of infection-related complications.MethodsClinical Practice Research Datalink identified 4 million acute infection episodes prescribed an antibiotic in primary care between January 2014—June 2014, England. Prescriptions were categorized by duration. Risk of infection-related hospitalizations within 30 days was modelled overall and by infection type. Risk was assessed immediately after or within 30 days follow-up to measure confounders given similar and varying exposure, respectively. An interaction term with follow-up time assessed whether hazard ratios (HRs) remained parallel with different antibiotic durations.ResultsThe duration of antibiotic courses increased over the study period (5.2–19.1%); 6–7 days were most common (66.9%). Most infection-related hospitalizations occurred with prescriptions of 8–15 days (0.21%), accompanied by greater risk of infection-related complications compared to patients who received a short prescription (HR: 1.75 [95% CI: 1.54–2.00]). Comparing HRs in the first 5 days versus remaining follow-up showed longer antibiotic courses were no more effective than shorter courses (1.02 [95% CI: 0.90–1.16] and 0.92 [95% CI: 0.75–1.12]). No variation by infection-type was observed.ConclusionsEqual effectiveness was found between shorter and longer antibiotic courses and the reduction of infection-related hospitalizations. Stewardship programs should recommend shorter courses of antibiotics for acute infections. Further research is required for treating patients with a complex medical history.SummaryPrescribing of longer courses increased over the study period. The majority of hospitalizations occurred for patients receiving longer courses. Risk of developing a complication (immediate vs remaining follow-up) found longer courses were no more effective than shorter courses.