Clinical Data on Daptomycin Plus Ceftaroline Versus Standard of Care Monotherapy in the Treatment of Methicillin-Resistant

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Antimicrobial agents and chemotherapy


Vancomycin (VAN) and daptomycin (DAP) are approved as monotherapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. A regimen of daptomycin plus ceftaroline (DAP+CPT) has shown promise in published case series of MRSA salvage therapy, but no comparative data exist to compare up front DAP+CPT head-to-head vs. standard monotherapy as initial treatment.In a pilot study, we evaluated 40 adult patients who were randomized to receive DAP 6-8 mg/kg/d + CPT 600 mg IV q8 h (n=17) or standard monotherapy (n=23) with vancomycin (VAN, dosed to achieve serum trough concentrations 15-20 mg/L, n=21) or DAP 6-8 mg/kg/d (n=2). Serum drawn on the first day of bacteremia was sent to a reference laboratory post-hoc for measurement of IL-10 concentrations and correlation to in-hospital mortality.Sources of bacteremia, median Pitt bacteremia scores, Charlson comorbidity indices, and median serum IL-10 serum concentrations were similar in both groups. Although the study was initially designed to examine bacteremia duration, we observed an unanticipated in-hospital mortality difference of 0% (0/17) for combination and 26% (6/23) for monotherapy (P=0.029), causing us to halt the study. Among patients with IL-10 > 5 pg/mL, 0% (0/14) died in the DAP+CPT group vs. 26% (5/19) in the monotherapy group (P=0.057). Here we share the full results of this preliminary (but aborted) assessment of early DAP+CPT versus standard monotherapy in MRSA bacteremia, hoping to encourage a more definitive clinical trial of its potential benefits against this leading cause of infection associated mortality.

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