Background: Long-term oral antibiotic regimens are increasingly prescribed in place of outpatient parenteral antimicrobial therapy(OPAT). Many of these oral agents are used at higher doses and for longer durations than studied previously. The aim of this study was to describe the rates of adverse drug events (ADEs) among patients discharged on long-term oral antibiotic regimens at our center.
Methods: This is a retrospective cohort study of adult patients discharged between January 1, 2021, and December 31, 2022, on oral antibiotic regimens of at least two weeks planned duration under the direction of an Infectious Diseases (ID) physician. The primary outcome was the occurrence of an ADE while on antibiotics up to ninety days after discharge.
Results: Of 174 patients included, 46 (26%) experienced at least one ADE. Gastrointestinal ADE were most common, and were most frequently associated with linezolid (11.3 ADE/1,000 COpAT-days), rifampin (8.0 ADE/1,000 COpAT-days), and fluoroquinolones (5.4 ADE/1,000 COpAT-days). Other ADE included hyperkalemia and nephrotoxicity from trimethoprim-sulfamethoxazole (3.9 and 6.2 ADE/1,000 COpAT-days respectively), and bone marrow suppression from linezolid (7.5 ADE/1,000 COpAT-days). Linezolid (22.6 ADE/1,000 COpAT-days, 95% CI [9.81-35.39]) and trimethoprim-sulfamethoxazole (14.61 ADE/1,000 COpAT-days, [9.00-20.23]) were associated with the highest rates of ADE, while amoxicillin-clavulanate (3.28 ADE/1,000 COpAT-days, [0.66-5.91]), tetracyclines (3.28 ADE/1,000 COpAT-days, [0.07-6.50]), and amoxicillin (5.80 ADE/1,000 COpAT-days, [0.00-12.37]) had the lowest.
Conclusion: Most patients tolerated oral therapy well with gastrointestinal adverse events being the most common ADE. Linezolid and trimethoprim-sulfamethoxazole were associated with the highest rates of adverse events.
Reference:Siddique N, Benefield RJ, Cummins H, Certain LK. Pills and ills: adverse events associated with oral antibiotics for prolonged durations of COpAT treatment courses. Antimicrob Steward Healthc Epidemiol. 2026 May 5;6(1):e123. doi: 10.1017/ash.2026.10373. PMID: 42112045; PMCID: PMC13150467.