Association of Higher Daptomycin Dose (7mg/kg or Greater) with Improved Survival in Patients with Methicillin-Resistant Staphylococcus aureus Bacteremia

Study ObjectiveCurrent guidelines recommend higher daptomycin doses than the daptomycin label dose of 6mg/kg for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia; however, the evidence supporting this recommendation is from invitro and case series studies. This study evaluated the comparative effectiveness of the daptomycin label dose versus higher daptomycin doses in patients with MRSA bacteremia. DesignRetrospective national cohort study. SettingVeterans Affairs medical centers. PatientsA total of 371 adults with MRSA bacteremia who were admitted between 2002 and 2015 and treated initially with vancomycin within 24hours of initial culture collection and then switched to daptomycin therapy within 7days; 138 patients (37.2%) received daptomycin doses higher than the daptomycin label dose (7mg/kg or greater), and 233 (62.8%) received the daptomycin label dose (6mg/kg). Measurements and Main ResultsClinical outcomes were compared among those who received the daptomycin label dose and those who received the higher dose using propensity score-matched Cox proportional hazards regression models. To identify dose partitioning associated with optimal survival, classification and regression tree (CART) analysis was used among patients, controlling for confounding with a 30-day mortality disease risk score. Propensity score-matched 30-day mortality was 8.6% (6/70 patients) among the higher dose group versus 18.6% (13/70 patients) among the label dose group (hazard ratio 0.31, 95% confidence interval 0.10-0.94). No significant differences were observed in inpatient mortality, length of stay, 30-day readmission, or 30-day S. aureus reinfection between groups. CART analysis resulted in doses of 7mg/kg or greater providing benefit only among patients with higher (more than 51%) predicted probabilities of 30-day mortality (p<0.001). ConclusionTo our knowledge, this is the first comparative effectiveness study of daptomycin doses in patients with MRSA bacteremia. Survival benefits were observed with doses higher than the daptomycin label dose (7mg/kg or greater) for the treatment of MRSA bacteremia. These data suggest that higher doses than the daptomycin label dose may be preferred over the label dose for improving clinical outcomes in patients with MRSA bacteremia.