Comparative Effectiveness of Cloxacillin/Cefazolin versus Vancomycin Empiric Therapy for Methicillin-susceptible Staphylococcus aureus (MSSA) Bacteremia Davie Wong MD1, Titus Wong MD2, Marc Romney MD2, Victor Leung MD2 1. Infectious Diseases Residency Training Program PGY-5, University of British Columbia, Vancouver, Canada. 2. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada. INTRODUCTION RESULTS RESULTS Staphylococcus aureus is the leading cause of bacteremia and Table 1: Baseline characteristics and clinical outcomes of patients with methicillin-susceptible S. aureus bacteremia. carries a mortality of 20-30% [1]. Empiric vancomycin is Patient characteristics β-lactam (n=131) Vancomycin (n=124) P-value commonly prescribed for patients with S. aureus bacteremia Age (years) 53.2 ± 16.5 59.4 ± 18.3 0.005 (SAB) to cover methicillin-resistant S. aureus (MRSA) as up to Community-onset 108 (82.4) 88 (71.0) 0.03 50-60% of bloodstream isolates are methicillin-resistant at some centres [2,3]. Charlson comorbidity index 3 (1.0-6.0) 4 (1.0-7.0) 0.001 Infectious diseases consultation 98 (74.8) 80 (64.5) 0.07 However, vancomycin is inferior to semi-synthetic anti- Infective endocarditis 24 (18.3) 12 (9.7) 0.05 Staphylococcal penicillins and first generation cephalosporins for the treatment of methicillin-susceptible Staphylococcus aureus Surgical source control 33 (25.2) 19 (15.3) 0.05 (MSSA) bacteremia [4]. Vancomycin is associated with higher Empiric antimicrobials rates of infection-related mortality, re-infection and bacteriologic Vancomycin 88 (67.2) 123 (99.2) <0.001 failure compared to cloxacillin or cefazolin in the definitive Cloxacillin or cefazolin 131 (100.0) 0 (0.0) <0.001 treatment of MSSA bacteremia [4,5]. 3rd generation cephalosporin 40 (30.5) 0 (0.0) <0.001 Early studies suggested that empiric vancomycin may be inferior Piperacillin-tazobactam 33 (25.2) 0 (0.0) <0.001 to empiric β-lactam [2,6,7]. Although controversial, some experts Other 47 (35.9) 66 (53.2) 0.01 recommend empiric combination therapy with vancomycin plus Duration of empiric therapy (hours) 54 (42.0-69.0) 48 (29.6-75.8) 0.28 Figure 1: Patient enrollment process. Abbreviations: MSSA, cloxacillin or cefazolin for patients at the highest risk of Duration of definitive therapy (days) 31.5 (13.0-42.0) 28 (10.0-42.0) 0.17 methicillin-susceptible S. aureus; BSI, bloodstream infection. morbidity and mortality from SAB [8]. However, no studies have Time to receipt of empiric therapy (hours) 2 (0-7) 20.9 (4.2-28.3) <0.001 directly compared cloxacillin or cefazolin to vancomycin as CONCLUSIONS empiric therapy for patients with MSSA bacteremia who are Time to receipt of β-lactam (hours) 3.00 (0.2-16.3) 68.2 (51.5-95.4) <0.001 transitioned to cloxacillin or cefazolin as definitive therapy. We Time to receipt of cloxacillin or cefazolin (hours) 21.0 (4.4-31.2) 68.3 (51.6-95.4) <0.001 Empiric therapy with cloxacillin or cefazolin was associated with assessed if empiric cloxacillin or cefazolin compared to earlier clearance of bacteremia by a median of 1 day compared to vancomycin was associated with differences in survival and Primary outcome vancomycin, but was not associated with a difference in all-cause microbiological cure in this patient population. 28-day mortality 7 (5.3) 11 (8.9) 0.27 mortality in patients with MSSA bacteremia. Vancomycin Secondary outcomes monotherapy for the empirical treatment of MSSA bacteremia 90-day mortality 14 (10.7) 22 (17.7) 0.11 may be appropriate if definitive therapy with cloxacillin or MATERIALS & METHODS cefazolin can be initiated within 3 days. Duration of bacteremia (hours) 70.7 (46.9-119) 97.1 (61.6-148) 0.007 We performed a retrospective cohort study of adult inpatients ≥ 3 days 58 (50) 72 (63.2) 0.047 REFERENCES with their first episode of MSSA bacteremia at two tertiary care Hospital length of stay (days) 19 (12-41) 22.5 (13-46.5) 0.16 hospitals in Vancouver, Canada, between January 2007 and 1. Thwaites GE, Edgeworth JD, Gkrania-Klotsas E et al. Clinical management of December 2014, inclusive. Consecutive patients were included if Staphylococcus aureus bacteraemia. Lancet Infect Dis 2011; 11: 208-222. Table 2: Outcome analysis comparing β-lactam versus vancomycin group, adjusted for predefined confounding variables. Abbreviations: they received cloxacillin or cefazolin for definitive therapy. 2. Khatib R, Saeed S, Sharma M et al. Impact of initial antibiotic choice and OR, odds ratio; CI, confidence interval. delayed appropriate treatment on the outcome of Staphylococcus aureus bacteremia. 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