The efficacy and safety of daptomycin: first in a new class of antibiotics for Gram-positive bacteria.
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.
Rybak
M J
MJ
Anti-Infective Research Laboratory, Wayne State University, Detroit, Michigan 48201, USA. m.rybak@wayne.edu
D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000592:standards* / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000639:trends; D017576:Daptomycin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000592:standards* / Q000627:therapeutic use; D024881:Drug Resistance, Bacterial; D004357:Drug Synergism; D064420:Drug-Related Side Effects and Adverse Reactions; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D017576:Daptomycin