Daptomycin

Daptomycin is a lipopeptide antibiotic. It is active only against Gram-positive organisms. It is a true antibiotic in that it is a naturally occurring compound which is found in the soil saprophyte, Streptomyces roseosporus; the compound was initially called LY146032 and was first discovered by Eli Lilly in the 1980's (Counter 1984) as part of their drug development programme. The rights to LY146032 were bought by Cubist Pharmaceuticals in 1997, who brought it to the US market in Nov 2003 as Cubicin®. more...

The current US product licence is only for skin and skin structure infections, but is most commonly reserved for systemic infections resistant to older antibiotics and is often used outside of its product licence. It is currently (14 Nov 2005) not available outside of the US.

Pharmacology

Daptomycin has a half-life of 8 hours. It is given intravenously once daily at a licenced dose of 4mg/kg once daily. A dose of 6mg/kg has been suggested for the treatment of endocarditis (Mohan 2005).

Daptomycin is only active against Gram-positive bacteria. The precise mechanism of action is currently (13 Nov 2005) unknown; it is known that daptomycin requires calcium ions in order to work, and that the end result is bacterial cell membrane depolarisation and cell death.

It has proven in vitro activity against Enterococci (including glycopeptide-resistant Enterococci (GRE)), Staphylococci (including methicillin-resistant Staphylococcus aureus), Streptococci and Corynebacteria. Although Daptomycin is active against Streptococcus pneumoniae, it cannot be used to treat pneumonia as it is inactivated by lung surfactant.

There is in vitro evidence of synergy with β-lactam antibiotics.

External links and References

• Cubicin (daptomycin for injection). URL accessed on November 13, 2005.
• UCSF monograph
• Counter FT et al (1984). "LY146032". Program Abstr 24th Intersci Conf Antimicrob Agents Chemother, abstr no 1078.
• Mohan SS, McDermott BP, Cunha BA (2005). Methicillin-resistant Staphylococcus aureus prosthetic aortic valve endocarditis with paravalvular abscess treated with daptomycin. Heart Lung 34 (1): 69–71.

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