Journal of Antimicrobial Chemotherapy (2000) 46, 523-526
© 2000 The British Society for Antimicrobial Chemotherapy
Leading article |
Development of daptomycin for Gram-positive infections
Cubist Pharmaceuticals, Inc., 24 Emily Street, Cambridge, MA 02139, USA
Gram-positive bacteria are an important cause of serious infections, particularly those originating in hospitals, and are becoming increasingly resistant to many antibiotics hitherto regarded as standard therapy for these infections.1 Daptomycin is an investigational antibiotic that kills most clinically significant Gram-positive bacteria.2–4 These include resistant pathogens for which there are very few therapeutic alternatives, such as vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide intermediately susceptible S. aureus (GISA), coagulase-negative staphylococci (CNS) and penicillin-resistant Streptococcus pneumoniae (PRSP).
The cyclic lipopeptide daptomycin (Figure 1
) is a fermentation product of Streptomyces roseosporus. It was discovered in the early 1980s, at Eli Lilly and Company (Lilly), and was developed as LY 146032 for intravenous treatment of serious Gram-positive infections. Nineteen Phase 1 and two Phase 2 clinical studies involving more than 370 subjects were conducted in the 1980s and early 1990s. The results in skin and soft tissue infections and bacteraemia
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