The efficacy and safety of daptomycin: first in a new class of antibiotics for Gram-positive bacteria

Clin Microbiol Infect. 2006 Mar;12 Suppl 1:24-32. doi: 10.1111/j.1469-0691.2006.01342.x.

Abstract

In the face of increasing resistance to currently available antibiotics, there is a continued interest in the development of new drugs to treat Gram-positive infections. One such agent is the cyclic lipopeptide daptomycin-licensed in the USA for treatment of Gram-positive complicated skin and skin structure infections (cSSSIs) in 2003 and currently awaiting European approval for a similar indication (complicated skin and soft tissue infections). Daptomycin exerts its rapid bactericidal effect through insertion into and subsequent depolarisation of the bacterial cell membrane, a mode of action unlike that of any other available antibiotic. This novel mechanism of action makes the development of cross-resistance between daptomycin and other antibiotic classes unlikely. Daptomycin is highly active in vitro against a range of Gram-positive pathogens, including both susceptible and multidrug-resistant staphylococci and enterococci. Bactericidal activity has also been demonstrated against both growing and stationary-phase organisms, suggesting potential utility in the treatment of deep-seated infections. Two pivotal clinical studies comparing daptomycin 4 mg/kg per day intravenously with vancomycin or oxacillin-class antibiotics demonstrated the efficacy of daptomycin for treatment of cSSSIs. Daptomycin was well tolerated, with most adverse events considered to be unrelated to study medication, of mild-to-moderate intensity, and with a frequency and distribution similar to those associated with comparator antibiotics. The favourable clinical profile and low potential for development of resistance combine to make daptomycin a promising alternative to current agents for treatment of Gram-positive bacterial infections.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / standards*
  • Anti-Bacterial Agents / therapeutic use
  • Clinical Trials as Topic / trends
  • Daptomycin / pharmacokinetics
  • Daptomycin / pharmacology
  • Daptomycin / standards*
  • Daptomycin / therapeutic use
  • Drug Resistance, Bacterial
  • Drug Synergism
  • Drug-Related Side Effects and Adverse Reactions
  • Gram-Positive Bacteria / drug effects*
  • Gram-Positive Bacterial Infections / drug therapy*
  • Humans
  • Staphylococcal Infections / drug therapy
  • Staphylococcus aureus / drug effects
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Daptomycin