P1482 Poster Session VI Epidemiology and clinical impact of S. aureus resistance BETA-LACTAMS VERSUS FOR TREATMENT OF -SUSCEPTIBLE STAPHYLOCOCCUS AUREUS BACTEREMIA: A RETROSPECTIVE COHORT STUDY OF DATA FROM THE U.S. VETERANS HEALTH ADMINISTRATION J.S. McDanel1, E.N. Perencevich2, D.J. Diekema1, L.A. Herwaldt1, T.C. Smith3, E.A. Chrischilles4, J.D. Dawson5, M.L. Schweizer2 1Internal Medicine, University of Iowa, Iowa City IA, USA ; 2CADRE, Iowa City VA Health Care System, Iowa City IA, USA ; 3College of Public Health, Kent State University, Kent OH, USA ; 4Epidemiology, University of Iowa, Iowa City IA, USA ; 5Biostatistics, University of Iowa, Iowa City IA, USA

Objectives: Results of previous small studies indicated that vancomycin is inferior to β-lactams for treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. However, it is unclear if this association remains for both empiric and definitive treatment. Our objective was to compareβ- lactams with vancomycin for empiric and definitive treatment of MSSA bacteremia.

Methods: This retrospective cohort study included patients admitted to all U.S. Veteran’s Affairs (VA) hospitals between 2003 and 2011 that had positive blood cultures for MSSA. The outcome was 30-day all-cause mortality. Cox proportional hazard models were used to assess mortality hazards comparing β-lactams versus vancomycin. A modified APACHE III severity of illness score (APACHE) on admission and Charlson Comorbidity Index were retained in all models regardless of statistical significance. Empiric treatment was defined as receipt of an antibiotic during the period 2 days before to 4 days after the culture collection; follow-up began when treatment was initiated. Definitive treatment was defined as starting or remaining on treatment during the period 4 to 14 days after culture collection. Optimal β-lactam therapy was defined as antistaphylococcal (, ) or first- generation (cephalexin, , ). Patients who received both vancomycin and a β-lactam empirically were removed from the empiric therapy analysis, similarly those who received both definitively were removed from the definitive analysis.

Results: 11,176 patients with MSSA bacteremia were included and 18% died within 30 days. Among the 9,861 patients who received empiric antibiotic treatment with vancomycin or a β-lactam, 16% received a β-lactam alone, 19% received vancomycin alone and 65% received both. Pipericillin/ (14%) was the most common β-lactam that patients received for empiric treatment. Empiric treatment with any β-lactam was associated with increased mortality compared with empiric vancomycin (adjusted hazards ratio [aHR]: 1.19, 95% CI: 1.00-1.42), after statistically adjusting for APACHE, comorbidities, co-infections, dual therapy with quinolones, and body mass index. However, there was a trend toward a protective effect of empiric therapy with optimal β-lactams compared with empiric vancomycin (aHR: 0.82, 95% CI: 0.64-1.05).

Among the 4,802 patients who received definitive treatment with vancomycin or a β-lactam, 9% received vancomycin, 83% received β-lactams, and 8% received both. Among patients who received definitive β-lactam treatment, 60% received cefazolin or nafcillin. Definitive treatment with anyβ-lactam was associated with a 34% decreased hazard of mortality compared with definitive treatment with vancomycin (aHR: 0.66; CI: 0.50-0.87), after adjusting for APACHE, comorbidities, age, osteomyelitis infection and allergy. The significantly protective effect remained when definitive optimal β- lactam treatment was compared with definitive vancomycin treatment (aHR: 0.62, 95% CI: 0.47-0.83).

Conclusion: For patients with MSSA bacteremia, β-lactams appear to be superior to vancomycin for definitive treatment. However, early receipt of β-lactam therapy may not prevent unfavorable outcomes from occurring.