Daptomycin | Encyclopeptide

Chemical Identity

Property	Value
Chemical Formula	C72H101N17O26
Molecular Weight	1620.67 Da
CAS Number	103060-53-3
Peptide Class	Cyclic Lipopeptide
Origin	Streptomyces roseosporus

Structure

Daptomycin is a cyclic lipopeptide consisting of 13 amino acids, including several non-standard residues (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. The molecule has a distinctive kynurenine residue essential for activity.

Mechanism of Action

In the presence of physiological calcium concentrations, daptomycin oligomerizes and inserts into the gram-positive bacterial cytoplasmic membrane, forming ion channels that cause rapid depolarization. This loss of membrane potential leads to inhibition of DNA, RNA, and protein synthesis, resulting in bacterial cell death without lysis.

Clinical Applications

MRSA bacteremia and right-sided endocarditis: FDA-approved
VRE infections: Including complicated UTIs
Skin and skin structure infections: MRSA and streptococcal
Osteomyelitis: Off-label with 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 (higher doses for severe infections)
Route: IV only

Safety and Side Effects

Myopathy and rhabdomyolysis (dose-dependent, especially >8 mg/kg or with concurrent statins), eosinophilic pneumonia, CPK elevation, and injection site reactions. CPK monitoring recommended weekly.

References

Arbeit, R.D., et al. (2004). Daptomycin for skin and skin structure 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.