Safety and Clinical Outcomes when Utilizing High-Dose (≥8 mg/kg) Daptomycin Therapy

作者：Pamela A. Moise, Ellie Hershberger, Maria I Amodio-Groton, Kenneth C. Lamp · 发表于：Annals of Pharmacotherapy · 年份：2009 · DOI：10.1345/aph.1m085 · 被引用次数：134 · 研究领域：Antimicrobial Resistance in Staphylococcus、Ocular Infections and Treatments、Infective Endocarditis Diagnosis and Management

BACKGROUND: Daptomycin is approved for the treatment of skin and skin-structure infections (4 mg/kg) and Staphylococcus aureus bacteremia, including right-sided endocarditis (6 mg/kg). In vitro and animal studies have reported increased activity with increased daptomycin doses. There are limited clinical data on use of daptomycin at doses greater than 6 mg/kg. OBJECTIVE: To evaluate the safety and efficacy of higher doses (> or =8 mg/kg) of daptomycin when administered for a variety of gram-positive infections. METHODS: Data were collected retrospectively as part of an ongoing registry (the Cubicin Outcomes Registry and Experience database) for the 2005-2007 program years. For the purpose of this study, the safety and efficacy of daptomycin were evaluated in patients who received doses of 8 mg/kg or higher. RESULTS: Ninety-four (2.6%) of 3617 patients received daptomycin doses of 8 mg/kg or higher; 18 (19%) of those patients received doses of 10 mg/kg or higher. The most common infections were bacteremia (30/94), skin and skin-structure infections (22/94), and endocarditis (15/94). The most common pathogens were Enterococcus spp. (37/94; 57% vancomycin-resistant) and S. aureus (28/94; 68% methicillin-resistant). Fifty-one percent of the patients were male, 39% were aged 66 years or older, 27% had an initial creatinine clearance less than 30 mL/min, and 17% were on dialysis. The median duration of daptomycin therapy was 15 days (minimum 1, maximum 90). Six (6.4%) of the 94 pat...