Daptomycin is a newly-approved antibacterial agent, the first lipopeptide agent to be released onto the market. Its spectrum of activity is limited to Gram-positive organisms, including a number of highly resistant species (MRSA, VISA, VRSA, VRE). It appears to be more rapidly bactericidal than vancomycin. Daptomycin has been approved for the treatment of complicated skin and soft tissue infections. Trials assessing daptomycin’s efficacy in treating complicated urinary tract infections and endocarditis/bacteremia are ongoing.
·Daptomycin is a nautral product derived from Streptomyces roseosporus. The drug was originally developed by Lilly in the early 1980s but was abandoned after early clinical trials.
·Daptomycin’s structure consists of a 13-member amino acid peptide linked to a 10-carbon lipophilic tail. This structure results in a novel mechanism of action, the disruption of the bacterial membrane through the formation of transmembrane channels. These channels cause leakage of intracellular ions leading to depolarizing the cellular membrane and inhibition of macromolecular synthesis.
·Daptomycin has rapid bactericidal activity. In vitro time-kill studies have demonstrated faster killing of S. aureus (including MRSA) and Enterococci (including VRE) compared to vancomycin.·Daptomycin displays concentration-dependent killing, with efficacy predicted best by Cmax/MIC and AUC/MIC ratios. The drug possesses a significant post-antbiotic effect, with growth inhibition occurring up to 6 hours after drug exposure.
·Bacteria in the stationary growth phase, as occurs in endocarditis or foreign body infections, may be better inhibited by daptomycin compared to vancomycin or nafcillin.
Daptomycin is unable to permeate the outer membrane of Gram-negative bacteria, thus its spectrum is limited to Gram-positive organisms only. Daptomycin has activity against Staphylococci (including MRSA, VISA, and VRSA), Enterococci (both E. faecalis and E.faecium, including VRE), and Streptococci (including DRSP), as well as most other aerobic and anaerobic Gram-positive bacteria.
Chemical name:
N-decanoyl-L-tryptophyl-D-asparaginyl-L-aspartyl-L-threonylglycyl-L-ornithyl-L-aspartyl-D-alanyl-L-aspartylglycyl-D-seryl-threo-3-methyl-L-glutamyl-3-anthraniloyl-L-alanine ε1-lactone.
Empirical formula: C72H101N17O26; Molecular weight is 1620.67.
Technical Data
Strain and technological know-how for fermentation and recovery is available
Final titre:1.7- 2.0g/L
Fermentation time: 260hrs
Recovery Yield: >50%
Strain: Streptomyces roseosporus
Technical status: above pilot plant
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