Background: Daptomycin-β-lactam (DAP-BL) combinations demonstrate in vitro synergy against MRSA; however, the clinical efficacy of combo are limited. Our objective was to compare the outcomes of patients (pts) with persistent MRSA bacteremia treated with DAP-BL combinations.
Methods: Retrospective, cohort study of hospitalized pts receiving DAP with ceftaroline (CPT) or oxacillin (OXA) between 3/2012 and 2/2018. Pts with persistent MRSA bacteremia despite ≥4 days of vancomycin therapy were included. Clinical success was defined as resolution of signs and symptoms of infection, microbiological eradication and in hospital survival.
Results: 32 pts included. 44% were male, median age was 61 (range: 26-78), and the median Charlson score was 2 (range: 0-11). 16% were IVDU. Sources of bacteremia included endocarditis (31%), bone/joint (31%), skin soft tissue (28%), and catheter (25%); 53% had more than one source. At the onset of combo therapy, median Pitt Bacteremia score was 1 (0-7). ID was consulted in all pts. 23 and 9 pts received DAP in combo with CPT or OXA, respectively. Baseline demographics, underlying disease, and clinical characteristics were comparable between groups. Pts receiving DAP-CPT had higher median Pitt Bacteremia scores (2 vs 1; p=0.04) and shorter median durations of prior vancomycin (8 vs 10 days; p= 0.02) than did pts receiving DAP-OXA. Source control was pursued equally between groups. Median time to clearance of bacteremia following combo therapy was 3 (0-24) vs 2 (-1-16) days in the DAP-CPT and DAP-OXA groups, respectively (p=0.45). Corresponding rates of clinical success (43% vs 56%) and microbiologic eradication (78% for both) did not vary between groups (Figure). In hospital mortality occurred in 39% of pts receiving DAP-CPT and 0% of pts receiving DAP-OXA (p=0.03). Adverse events occurred in 35% and 44% of pts, respectively.
Conclusion: We have demonstrated high rates of microbiologic eradication and reasonable clinical success rates with DAP-BL combination therapy. Pts receiving DAP-CPT had higher severity of illness at baseline, which paralleled with higher mortality. These data provide compelling evidence for future studies designed to determine the optimal BL in combination with DAP for persistent MRSA bacteremia.
R. K. Shields, Allergan: Grant Investigator , Research grant . Pfizer: Consultant and Scientific Advisor , Speaker honorarium . Shionogi: Scientific Advisor , Consulting fee . Roche: Grant Investigator , Research grant . Venatorx: Grant Investigator , Research grant . Medicines Company: Grant Investigator and Scientific Advisor , Consulting fee and Research grant . Accelerate Diagnostics: Scientific Advisor , Consulting fee .