Daptomycin: A cyclic lipopeptide antimicrobial agent

Jeu, LilyAnn; Fung, Horatio B.

OBJECTIVES: The aims of this article were: to summarize the pharmacology, pharmacokinetics, and efficacy ofdaptomycin; to explore its safety profile; and to discuss its current and potential roles as an antimicrobial therapy. METHODS: A literature search was conducted using the MEDLINE (1966–August 2004) and InternationalPharmaceutical Abstracts (1970–August 2004) databases with the search terms daptomycin, LY146032, and lipopeptide antibiotics. Abstracts of the Interscience Conference on Antimicrobial Agents and Chemotherapy and documents submitted to the US Food and Drug Administration were also reviewed. RESULTS: Phase III study results suggest no difference in efficacy or tolerability between daptomycin 4 mg/kgIV QD and vancomycin or semisynthetic penicillins for complicated skin and skin-structure infections. Animal studies suggest daptomycin may be useful for the treatment of endocarditis. Daptomycin is not indicated for pneumonia, with poorer outcomes than conventional treatment It is available as an IV medication and exhibits 92% plasma protein binding in vitro. In healthy adult humans, daptomycin has a volume of distribution of 0.1 Ukg and a plasma elimination half-life of ∼9 hours, and is eliminated primarily by renal excretion (∼54%). In patients with reduced renal function, including those receiving hemodialysis and peritoneal dialysis, the dose interval should be 48 hours. No dosage adjustment appears to be necessary for mild to moderate hepatic impairment. The use of daptomycin in patients with severe hepatic impairment has not been assessed. The most commonly reported adverse events include constipation, nausea, injection-site reactions, headache, and diarrhea. Patients should also be monitored regularly for skeletal muscle toxicity. CONCLUSIONS: Daptomycin may be useful for complicated skin and skin-structure infections and gram-positive pathogens resistant to conventional antimicrobials. However, limited data are currently available for duration of treatment beyond 14 days and at doses >4 mg/kg QD.