Daptomycin
Cyclic lipopeptide antibiotic that inserts into gram-positive bacterial membranes, causing rapid depolarization and cell death.
Chemical Identity
| Property | Value |
|---|---|
| Chemical Formula | C72H101N17O26 |
| Molecular Weight | 1620.67 Da |
| CAS Number | 103060-53-3 |
| Peptide Class | Cyclic Lipopeptide (13 amino acids) |
| Origin | Streptomyces roseosporus |
| Route | IV |
Structure
Daptomycin (Cubicin) is a cyclic lipopeptide consisting of 13 amino acids, including several non-standard residues such as L-kynurenine, L-3-methylglutamic acid, D-alanine, D-serine, and D-asparagine. A decanoyl fatty acid side chain is attached to the threonine at position 1, essential for membrane insertion activity.
Mechanism of Action
In the presence of physiological calcium concentrations, daptomycin oligomerizes and inserts into the gram-positive bacterial cytoplasmic membrane, forming ion conductance pathways. This causes rapid membrane depolarization, loss of membrane potential, inhibition of DNA/RNA/protein synthesis, and bacterial cell death without cell lysis.
Clinical Applications
- MRSA bacteremia and right-sided endocarditis: FDA-approved
- VRE infections: Including urinary tract infections
- Complicated skin infections: MRSA and streptococcal
- Bone and joint infections: Good bone penetration
Pharmacokinetics
- Half-life: 8-9 hours
- Protein binding: 90-93%
- Elimination: Renal (78% unchanged)
- Dosing: 4-6 mg/kg IV every 24 hours (8-10 mg/kg for severe infections)
- Route: IV infusion over 30 minutes
Safety and Side Effects
Myopathy and rhabdomyolysis (dose-dependent, CPK monitoring required), eosinophilic pneumonia (rare), injection site reactions, and GI disturbances. Avoid concurrent statins when possible.
References
- Arbeit, R.D., et al. (2004). Daptomycin for complicated skin infections. New England Journal of Medicine, 350, 1657-1664.
- Fowler, V.G., et al. (2006). Daptomycin versus standard therapy for bacteremia. New England Journal of Medicine, 355, 653-665.
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