Vancomycin (VAN) and
daptomycin (DAP) are approved as a 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
therapy versus standard monotherapy as an initial treatment. In a pilot study, we evaluated 40 adult patients who were randomized to receive 6 to 8 mg/kg of
body weight per day of DAP and 600 mg intravenous (i.v.)
CPT every 8 h (q8h) (n = 17) or standard monotherapy (n = 23) with
vancomycin (VAN; dosed to achieve serum trough concentrations of 15 to 20 mg/liter; n = 21) or 6 to 8 mg/kg/day DAP (n = 2). Serum drawn on the first day of
bacteremia was sent to a reference laboratory post hoc for measurement of
interleukin-10 (IL-10) concentrations and correlation to in-hospital mortality. Sources of
bacteremia, median Pitt
bacteremia scores, Charlson comorbidity indices, and median
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
therapy and 26% (6/23) for monotherapy (P = 0.029), causing us to halt the study. Among patients with an
IL-10 concentration of >5 pg/ml, 0% (0/14) died in the DAP+CPT group versus 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
therapy 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. (The clinical study discussed in this paper has been registered at ClinicalTrials.gov under identifier NCT02660346.).