ABSTRACT
BACKGROUND: Daptomycin and ceftaroline (DAP-CPT) have been used for persistent methicillin-resistant Staphylococcus aureus bacteremia (MRSAB), but have rarely been compared with other therapies. This study provides an exploratory analysis of patients placed on DAP-CPT vs standard of care (SOC) for MRSAB. METHODS: This is a retrospective, matched cohort study MRSAB patients at 4 hospitals in the United States. Patients receiving DAP-CPT for ≥72 hours at any point in therapy were matched 2:1 when possible, 1:1 otherwise, to SOC, first by infection source, then age and renal function. SOC was empiric treatment with vancomycin or daptomycin and any subsequent combination antibiotic(s), except for DAP-CPT. RESULTS: Fifty-eight patients received DAP-CPT with 113 matched SOC. Ninety-six percent of SOC received vancomycin, and 56% (63/113) escalated therapy at least once in the treatment course. Twenty-four patients received DAP-CPT within 72 hours of index culture; 2 (8.3%) died within 30 days vs 14.2% (16/113) with SOC (Pâ >â .05). Subgroup analysis identified numerically lower mortality in DAP-CPT patients with a Charlson comorbidity index ≥3, endovascular source, and receipt of DAP-CPT within 72 hours of index culture. The median MRSAB duration was 9.3 vs 4.8 days for DAP-CPT and SOC, respectively. DAP-CPT was initiated on day 6 on average; after receipt of DAP-CPT, MRSAB duration was 3.3 days. CONCLUSIONS: DAP-CPT treatment is often delayed in MRSAB. Combination therapy may be more beneficial if initiated earlier, particularly in patients at higher risk for mortality. Blinded, randomized, prospective studies are needed to eliminate selection bias inherent in retrospective analyses when examining DAP-CPT vs SOC.
ABSTRACT
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.).
