Evaluating Harms Associated with Prolonged Antibiotic Duration of Therapy in Community Dwelling Older Adults: A Cohort Study using Instrumental Variable Analysis

Background Shorter courses of antibiotic therapy are increasingly recommended to reduce antibiotic exposure. However quantifying the real-world impact of duration of therapy is hindered by bias common in observational studies. We aimed to evaluate the harms and benefits of longer versus shorter duration of therapy in older adults. Methods This was a population-based cohort study using administrative health data from Ontario, Canada. We included outpatients aged 66 to 110 years who received a prescription for amoxicillin, cephalexin, and/or ciprofloxacin. Prescriptions were categorized as short (3-7 days) or long (8-14 days) duration. The primary outcome was a composite of antibiotic-related harms, including adverse reactions, Clostridioides difficile infection, and antibiotic resistance. The secondary outcome was a composite of safety measures including repeat antibiotic prescriptions, hospital visits and mortality. To reduce risk of bias, we used an instrumental variable analysis where the instrument was prescriber proportion of antibiotics that were long duration. Results Among 117,682 eligible patients, there was no difference in the primary harms outcome for patients receiving longer versus shorter courses of antibiotics (amoxicillin ORadj 0.99 (95%CI 0.84 to 1.15), cephalexin ORadj 1.11 (95%CI: 0.90 to 1.38), ciprofloxacin ORadj 0.94 (95%CI 0.74 to 1.20). Secondary safety outcomes were similar, with longer compared to shorter courses of antibiotic therapy (amoxicillin OR 1.01 (95%CI: 0.94 to 1.08), cephalexin OR 1.06 (95%CI 0.97 to 1.17), ciprofloxacin OR 0.99 (95%CI: 0.85 to 1.15)). Conclusion In this instrumental variable analysis of community-dwelling older adults, longer antibiotic courses were not associated with an increased benefit or harm compared to shorter courses.