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The efficacy and safety of daptomycin: first in a new class of antibiotics for Gram-positive bacteria Rybak MJClin Microbiol Infect 2006[Mar]; 12 Suppl 1 (ä): 24-32In 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.|Anti-Bacterial Agents/pharmacokinetics/pharmacology/*standards/therapeutic use[MESH]|Clinical Trials as Topic/trends[MESH]|Daptomycin/pharmacokinetics/pharmacology/*standards/therapeutic use[MESH]|Drug Resistance, Bacterial[MESH]|Drug Synergism[MESH]|Drug-Related Side Effects and Adverse Reactions[MESH]|Gram-Positive Bacteria/*drug effects[MESH]|Gram-Positive Bacterial Infections/*drug therapy[MESH]|Humans[MESH]|Staphylococcal Infections/drug therapy[MESH]|Staphylococcus aureus/drug effects[MESH]|Treatment Outcome[MESH] |
