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

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.Retrospective, multicenter cohort study.Five academic or community hospitals throughout the United States.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.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<0.001).Receipt of COMBO therapy did not decrease the rate of clinical failure but was associated with expedited bacteremia clearance. Early adjuvant β-lactam therapy deserves continued evaluation and clinical consideration.