Daptomycin : a review of properties, clinical use, drug delivery and resistance

Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2014Daptomycin is a branched cyclic anionic lipopeptide antibiotic that was discovered in the early 1980's but only got the FDA approval in 2003. This novel pharmaceutical molecule has demonstrated great in vitro activity against a wide range of aerobic and anaerobic gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. Daptomycin has a unique mechanism of action, not completely understood, involving a calcium-dependent dissipation of membrane potential leading to the release of intracellular ions from the cell and bacteria death. This antibiotic has been already approved for the treatment of patients with complicated skin and skin structure infections, right-sided endocarditis and bacteraemia. Local delivery of daptomycin is an emerging area of study. Current in vitro studies show that daptomycin can be eluted from polymethylmethacrylate, calcium sulfate and chitosan films. Emerging cases of resistance to daptomycin have been reported, commonly occuring by spontaneous mutations, and has been associated with prolonged use, osteomyelitis, acute myeloid leukaemia and leucocyte adhesion deficiency syndrome. This review examines the most recent literature evidences on daptomycin molecular structure, mechanism of action, bacterial spectrum, clinical uses, local delivery, toxicity and resistance