Early Administration of Adjuvant β‐Lactam Therapy in Combination with Vancomycin among Patients with Methicillin‐Resistant Staphylococcus aureus Bloodstream Infection: A Retrospective, Multicenter Analysis

Study Objective To determine whether early administration of adjuvant β‐lactam in combination with vancomycin (COMBO) affects clinical outcomes compared to standard vancomycin therapy alone (STAN) among patients with methicillin‐resistant Staphylococcus aureus (MRSA) bloodstream infection. Design Retrospective, multicenter cohort study. Setting Five academic or community hospitals throughout the United States. Patients Adults with MRSA bloodstream infections treated with vancomycin (≥ 72 hrs) with or without an intravenous β‐lactam (≥ 48 hrs) initiated within 24 hours of initiating vancomycin. Measurements and Main Results The primary outcome was clinical failure, a composite endpoint including 30‐day mortality, persistent bacteremia (≥ 7 days), bacteremia relapse, or change in antibiotic therapy during treatment due to clinical worsening. A multivariable logistic regression examined the impact of patient‐, treatment‐, and pathogen‐level characteristics on clinical failure. A total of 201 patients were evaluated of whom 97 (48.3%) met the criteria for study inclusion; 40 (41.2%) in STAN and 57 (58.8%) in COMBO groups. Among patients in the STAN and COMBO groups, 30% and 24.6% experienced clinical failure, respectively (p=0.552). The median (interquartile range) duration of bacteremia in the STAN and COMBO groups was 4 days (2.5–6.5) and 3 days (2–5), respectively (p=0.048). In a multivariable analysis, receipt of COMBO therapy was inversely associated with clinical failure (adjusted odds ratio [aOR] 0.237, 95% confidence interval [CI] [0.057–0.982]; p=0.047). Other independent predictors of clinical failure included complicated bacteremia (aOR 6.856, 95% CI [1.641–28.649]; p=0.008) and antibiotic therapy not continued at discharge (aOR 45.404, 95% CI [9.383–219.714]; p