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Study Objective: As variability in vancomycin dosing, susceptibility, and tolerability has driven the need to compare newer agents with vancomycin in real-world clinical settings, we sought to quantify the effectiveness of linezolid compared with vancomycin on clinical outcomes for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia.

Design: Retrospective cohort study.

Data Source: Veterans Health Administration national databases.

Patients: Adults admitted to Veterans Affairs hospitals between January 2002 and September 2010 with diagnosis codes for MRSA and pneumonia, and who initiated and received at least 3 days of continuous intravenous vancomycin therapy (4943 patients) or intravenous or oral linezolid therapy (328 patients) while in the hospital.

Measurements and Main Results: Propensity score–adjusted Cox proportional hazards regression models quantified the effect of linezolid compared with vancomycin on time to 30-day mortality (primary outcome), therapy change, hospital discharge, discharge from intensive care, intubation, 30-day readmission, and 30-day MRSA reinfection. In addition, a composite outcome of clinical success was defined as discharge from the hospital or intensive care unit by day 14 after treatment initiation, in the absence of death, therapy change, or intubation by day 14. Subgroup analyses were performed in a validated microbiology-confirmed MRSA subgroup and clinical subgroup meeting clinical criteria for infection. Although a number of baseline variables differed significantly between the vancomycin and linezolid treatment groups, balance was achieved within propensity score quintiles. A significantly lower rate of therapy change was observed in the linezolid group (adjusted hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.48–0.96). The clinical success rate was significantly higher among patients treated with linezolid (adjusted HR 1.25, 95% CI 1.07–1.47). Comparable findings were observed in the subgroup analyses.

Conclusion: Individual clinical outcomes were similar among patients treated for MRSA pneumonia with linezolid compared with vancomycin. A significantly higher rate of the composite outcome of clinical success was observed, however, among patients treated with linezolid compared with vancomycin.