BACKGROUND Linezolid is an oxazolidinone antibiotic with activity against drug-resistant gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus. The typical duration of linezolid therapy is approximately two weeks, with a maximum recommended duration of 28 days per the package insert. Bone and joint infections often require prolonged courses of antimicrobial therapy of 4 to 6 weeks. Linezolid is an ideal agent for treatment of bone and joint infections due to its reliable oral bioavailability and activity against resistant organisms. However, concerns regarding hematologic and neurologic toxicity often limit extended use beyond recommended durations. Real-world data describing tolerability during prolonged outpatient therapy remains limited. This study evaluated treatment completion and adverse effects associated with extended-duration linezolid therapy in an outpatient cohort. METHODS We conducted a retrospective cohort study at a large academic medical center evaluating adults prescribed oral linezolid 600 mg every 12 hours for more than 14 days for bone and joint infections between January 2022 and December 2024. Laboratory data were evaluated at two-week intervals. Patients lacking follow up laboratory data after the first 14 days of therapy or who were lost to follow up were excluded. Baseline demographics, laboratory values, duration of therapy, and adverse effects were collected from electronic health records. The primary outcome was the completion of prescribed therapy. Secondary outcomes included incidence of hematologic toxicity, defined as thrombocytopenia (platelet count < 150 x 103/ mcL or 50% decrease from baseline) or anemia (hemoglobin ≤ 10 g/dL or 2 g/dL decrease from baseline), and neurologic toxicity defined by documented new-onset neuropathic or visual symptoms. Time to adverse events was also assessed.
