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INFECTIOUS DISEASES

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

Clinical Scientific Director, Cubist Pharmaceuticals Inc., Lexington, MA

Ellie Hershberger, PharmD

Clinical Scientific Director, Cubist Pharmaceuticals Inc.

Maria I Amodio-Groton, PharmD

Clinical Scientific Director, Cubist Pharmaceuticals Inc.

Kenneth C Lamp, PharmD

Senior Director of Registry Research, Cubist Pharmaceuticals Inc.

Reprints: Dr. Moise, Cubist Pharmaceuticals, 65 Hayden Ave., Lexington, MA 02421, fax 858/481-4076, pamela.moise{at}cubist.com

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 (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 patients experienced 1 or more adverse events or abnormal laboratory value changes possibly related to daptomycin; in 2 (2.1%) of the 94 patients, daptomycin was discontinued due to treatment-related adverse events. Seventy-four (79%) patients were considered evaluable for efficacy. The overall clinical success rate was 89% (bacteremia, 91%; skin and skin-structure infections, 88%; endocarditis, 67%).

CONCLUSIONS: Daptomycin was well tolerated and effective at doses of 8 mg/kg or higher in patients with gram-positive infections. Further prospective and comparative studies of daptomycin at doses greater than 6 mg/kg are warranted.

Key Words: daptomycin; daptomycin, higher doses; gram-positive infections

Published Online, July 7, 2009. www.theannals.com, DOI 10.1345/aph.1M085

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