Improving Definitive Therapy Among Patients with Methicillin-resistant Staphylococcus aureus Bloodstream Infections: Predictors of Early Therapeutic Switch to Linezolid or Daptomycin

BACKGROUND: Vancomycin is a first-line antibiotic for treating methicillin-resistant S. Aureus bloodstream infections (MRSA BSI), due to its activity against MRSA and low cost. If vancomycin fails, patients are often switched to daptomycin or linezolid. We aimed to determine predictors for switching from vancomycin to daptomycin or linezolid. Close follow-up and early identification of patients who may benefit from these newer antibiotics could improve outcomes. METHODS: Retrospective cohort study of all Veteran patients with MRSA BSI who began therapy on vancomycin from 2007 to 2014. Patients were followed for 30 days. Potential predictors of switching measured at the time of admission included demographics, diagnoses, and comorbidities. Co-infections were defined using ICD-9 codes. Additional predictors were time-varying during index admission, including: therapeutic level of vancomycin (defined as 24-hour area under concentration-time-curve to minimum inhibitory concentration [AUC/MIC] ≥ 400), lab values, and acute kidney injury (AKI, defined by change in creatinine). A Cox proportional hazards model was used to evaluate the association between predictors and the relative hazards of switching to daptomycin or linezolid. RESULTS: 17,841 patients had MRSA BSI and were given vancomycin initially. By 30 days, 18% of patients were therapeutically switched including 9.4% (n = 1,680) to daptomycin and 10.5% (n = 1,873) to linezolid. 4,763 (27%) patients had a therapeutic vancomycin dose within 5 days of initiating vancomycin, 1,318 (7%) had a subtherapeutic dose, and 11,760 (66%) could not have an AUC calculated. 5,692 (31.9%) patients experienced AKI after initiating vancomycin. Factors associated with increased likelihood of switching included subtherapeutic vancomycin dose (hazard ratio [HR] = 1.53; 95% confidence interval [CI]: 1.29, 1.82); AKI (HR = 1.51; 95% CI: 1.34, 1.70); co-infections with osteomyelitis (HR = 1.28; 95% CI: 1.13, 1.46), pneumonia (HR = 1.35; 95% CI: 1.10, 1.66) and endovascular infections (HR = 1.18; 95% CI: 1.05, 1.32). CONCLUSION: A high proportion of patients with MRSA bacteremia were therapeutically switched. Patients with co-infections may be targets for early daptomycin/linezolid therapy. Efforts should continue towards improving vancomycin dosing during the first 5 days of therapy. DISCLOSURES: M. Schweizer, B Braun: Speaker at a course, Travel reimbursement to teach course.