Clinical Data on Daptomycin Plus Ceftaroline Versus Standard of Care Monotherapy in the Treatment of Methicillin-Resistant
Geriak M, Haddad F, Rizvi K, Rose W, Kullar R, LaPlante K, Yu M, Vasina L, Ouellette K, Zervos M, Nizet V, and Sakoulas G. Clinical Data on Daptomycin plus Ceftaroline versus Standard of Care Monotherapy in the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia. Antimicrob Agents Chemother 2019; 63(5):e02483-18.
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.