Outcomes and Adverse Events Among Patients with Vancomycin-Resistant Enterococcal Bloodstream Infection Treated with Daptomycin Doses Greater than 12 mg/kg.

introductionDaptomycin is commonly used for vancomycin-resistant enterococcal bloodstream infections (VRE-BSIs); however, its optimal dosing remains uncertain. Although doses > 12 mg/kg may improve attainment of pharmacodynamic targets, clinical outcomes and safety data for very-high-dose daptomycin are limited.

methodsThis multicenter cohort study included adults with a VRE-BSI treated with daptomycin doses > 12 mg/kg, between 2011 and 2024. The primary outcome was 28-day all-cause mortality. Daptomycin-associated adverse events, including creatine kinase (CK) elevation, were assessed, and multivariable logistic regression models were used to identify factors associated with mortality and an elevated CK level.

resultsAmong 101 patients, the median age was 70.2 years, and 67.3% had an underlying malignancy. The 28-day mortality was 41.6% and was primarily associated with host factors and illness severity. Daptomycin dose was not associated with mortality when modeled as a continuous variable; however, in exploratory post hoc analysis, doses > 13 mg/kg were associated with lower mortality compared with 12-13 mg/kg [adjusted odds ratio (aOR), 0.22; 95% confidence interval (CI) 0.05-0.98; p = 0.047]. CK elevation occurred in 13.9% and was independently associated with higher daptomycin dose (aOR, 2.99; 95% CI 1.05-8.50). Eosinophilic pneumonia was identified in 10.9% of patients.

conclusionsIn patients with VRE-BSI treated with daptomycin doses > 12 mg/kg, mortality remained high and was primarily driven by host factors and severity of illness. Although exploratory findings suggest a potential mortality benefit at doses > 13 mg/kg, this must be balanced against a significantly increased risk of dose-related toxicity, including a notably high incidence of eosinophilic pneumonia.