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

Mini Rev Med Chem. 2012 Mar;12(3):202-9. doi: 10.2174/1389557511209030202.

Abstract

Daptomycin is a branched cyclic anionic lipopeptide antibiotic that was discovered in the early 1980's but got the FDA approval only 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 occurring by spontaneous mutations, and have been associated with prolonged use, osteomyelitis, acute myeloid leukemia 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.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use*
  • Daptomycin / administration & dosage
  • Daptomycin / chemistry
  • Daptomycin / pharmacology*
  • Daptomycin / therapeutic use*
  • Drug Resistance, Bacterial
  • Gram-Positive Bacteria / drug effects*
  • Gram-Positive Bacterial Infections / drug therapy*
  • Humans
  • Methicillin-Resistant Staphylococcus aureus / drug effects

Substances

  • Anti-Bacterial Agents
  • Daptomycin