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Purpose: The purpose of this study is to improve the quality of care and patient outcomes for Staphylococcus aureus bacteremia.Methods: A quasi-experimental pre- and postintervention study design was used to compare process and clinical endpoints before and after a quality-improvement initiative. All inpatients >18 years of age with a positive blood culture for S. aureus during the specified pre- and postintervention period with clinical information available in the electronic medical record were included. An institutional protocol for the care of patients with S. aureus bacteremia was developed, formalized, and distributed to providers using a pocket card, an electronic order set, and targeted lectures over a 9-month period.Results: There were 167 episodes of S. aureus bacteremia (160 patients) identified in the preintervention period, and 127 episodes (123 patients) in the postintervention period. Guideline adherence improved in the postintervention period for usage of transesophageal echocardiogram (43.9% vs 20.2%, P <.01) and adequate duration of intravenous therapy (71% vs 60%, P = .05). In a multivariate Cox proportional hazard model, the variables associated with increased relapse-free survival were postintervention period (hazard ratio [HR] 0.48; confidence interval [CI], 0.24-0.95; P .035) and appropriate source control (HR 0.53; CI, 0.24-0.92; P .027). Regardless of intervention, presence of cancer was associated with an increased risk of relapse or mortality at 90 days (HR 2.88; P <.0001; CI, 1.35-5.01).Conclusion: A bundled educational intervention to promote adherence to published guidelines for the treatment of S. aureus bacteremia resulted in a significant improvement in provider adherence to guidelines as well as increased 90-day relapse-free survival. [ABSTRACT FROM AUTHOR]