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Beta-Lactams versus Vancomycin for Treatment of Methicillin-susceptible Staphylococcus aureus Bacteremia: A Retrospective Cohort Study of Data from the U.S. Veterans Health Administration
McDanel JS, Perencevich EN, Diekema DJ, Herwaldt L, Smith T, Chrischilles E, Dawson J, Schweizer ML. Beta-Lactams versus Vancomycin for Treatment of Methicillin-susceptible Staphylococcus aureus Bacteremia: A Retrospective Cohort Study of Data from the U.S. Veterans Health Administration. Poster session presented at: European Society of Clinical Microbiology and Infectious Diseases Annual European Congress of Clinical Microbiology and Infectious Diseases; 2014 May 13; Barcelona, Spain.
Objectives: Results of previous small studies indicated that vancomycin is inferior to -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 compare -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 2010 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 -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 antibiotic 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 -lactam therapy was defined as antistaphylococcal penicillins (nafcillin, oxacillin) or first-generation cephalosporins (cephalexin, cefazolin, cefradine). Patients who received both vancomycin and a -lactam empirically were removed from the empiric therapy analysis, similarly those who received both antibiotics definitively were removed from the definitive analysis.
Results: 16,973 patients with MSSA bacteremia were included and 16% died within 30 days. Among the 14,307 patients who received empiric antibiotic treatment with vancomycin or a -lactam, 19% received a -lactam alone, 22% received vancomycin alone and 59% received both. Among patients who received empiric -lactam treatment alone, pipericillin/tazobactam (31%) was the most common -lactam that patients received for empiric treatment. There was a non-statistically significant trend toward empiric treatment with any -lactam being associated with increased mortality compared with empiric vancomycin (adjusted hazards ratio [aHR]: 1.11, 95% CI: 0.96-1.28), after statistically adjusting for APACHE, Charlson comorbidity score, age, community-acquired infection, ICU admission, co-infection, and dual therapy with quinolones or linezolid or trimethoprim-sulfamethoxazole. However, there was a trend toward a protective effect of empiric therapy with optimal -lactams compared with empiric vancomycin (aHR: 0.82, 95% CI: 0.65-1.03).
Among the 7,014 patients who received definitive treatment with vancomycin or a -lactam, 13% received vancomycin alone, 73% received -lactams alone, and 14% received both. Among patients who received definitive -lactam treatment alone, 60% received cefazolin or nafcillin. Definitive treatment with any -lactam was associated with a 26% decreased hazard of mortality compared with definitive treatment with vancomycin (aHR: 0.74; CI: 0.61-0.90), after adjusting for APACHE, Charlson, age, and osteomyelitis co-infection. The significantly protective effect remained when definitive optimal -lactam treatment was compared with definitive vancomycin treatment (aHR: 0.66, 95% CI: 0.54-0.82).
Conclusion: For patients with MSSA bacteremia, -lactams appear to be superior to vancomycin for definitive treatment. However, early receipt of -lactam therapy may not prevent unfavorable outcomes from occurring.