Combination Ceftaroline and Daptomycin Salvage Therapy for Complicated Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteremia Compared with Standard of Care.

Abstract Complicated methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI), particularly those with delayed culture clearance, are associated with high mortality. Combination therapy with daptomycin and ceftaroline (DAP+CPT) represents a novel therapeutic approach to MRSA BSI due to synergistic bactericidal activity. This study aimed to compare DAP+CPT to historical standard of care (SoC) for the treatment of complicated MRSA BSI. This single-center retrospective cohort study included patients with complicated MRSA BSI at the University of Colorado Hospital. Patients receiving DAP+CPT for ≥48 hours between November 2013 to March 2020 or SoC with vancomycin (VAN) or DAP ± gentamicin and/or rifampin from November 2011 to December 2013 were compared. Primary outcome was clinical failure, defined as a composite of MRSA-related mortality and recurrent infection at 60 days. Sixty patients received DAP+CPT (n=30) or SoC (n=30). Median age was 56 years and median Pitt Bacteremia Score was 3. Common infectious sites were endovascular (63%) and musculoskeletal (40%). DAP+CPT was associated with numerically lower incidence of clinical failure compared to SoC (20% vs 43%, p=0.052). A multiple-variable analysis controlling for immunocompromised status (OR [95% CI] =6.90 [1.08-44.15]), Charlson Comorbidity Index (OR [95% CI] =1.12 [0.90-1.39]), and source control (OR [95% CI] =0.35 [0.08-1.46]), associated DAP+CPT with 77% lower odds of clinical failure (OR [95% CI] =0.23 [0.06 to 0.89]). In patients with complicated MRSA BSI with delayed clearance, DAP+CPT trended towards lower rates of clinical failure than SoC and was significantly associated with decreased clinical failure after adjustment for baseline differences.