Daptomycin
Daptomycin is a cyclic lipopeptide antibiotic from Streptomyces roseosporus that disrupts bacterial cell membranes, approved for MRSA and VRE infections.
Chemical Identity
| Property | Value |
|---|---|
| Chemical Formula | C72H101N17O26 |
| Molecular Weight | 1620.67 g/mol |
| CAS Number | 103060-53-3 |
| IUPAC Name | Cyclic lipodepsipeptide |
| Peptide Class | Lipopeptide Antibiotic |
| Origin | Streptomyces roseosporus |
Structure
Daptomycin is a 13-amino acid cyclic lipopeptide produced by Streptomyces roseosporus. It contains a decanoyl fatty acid side chain attached to the N-terminal tryptophan, a kynurenine residue at position 2 (unique among natural products), and several non-standard amino acids including D-alanine, L-ornithine, D-serine, and D-alanine. The cyclic structure is formed via an ester bond (depsipeptide) between the threonine at position 13 and the carboxyl group of the C-terminal residue.
Mechanism of Action
Daptomycin binds to the bacterial cytoplasmic membrane in a calcium-dependent manner. In the presence of physiological calcium concentrations, it oligomerizes within the membrane, forming ion-conducting channels that cause rapid potassium efflux. This leads to membrane depolarization, loss of membrane potential, and cell death. Unlike beta-lactams, daptomycin is bactericidal against stationary-phase organisms.
Clinical Applications
Daptomycin (Cubicin) is approved for:
- Complicated skin and skin structure infections (cSSSI): Caused by gram-positive pathogens
- Staphylococcus aureus bacteremia: Including right-sided endocarditis
- Enterococcal infections: Vancomycin-resistant Enterococcus (VRE) faecium
Not effective for pneumonia (inactivated by pulmonary surfactant). Reserved for resistant infections due to cost and resistance concerns.
Pharmacokinetics
- Half-life: 8-9 hours
- Tmax: 0.5-0.8 hours
- Protein binding: 90-93% (primarily albumin)
- Metabolism: Not metabolized by CYP enzymes; renal elimination of unchanged drug
- Dosing: Once-daily intravenous infusion (4-8 mg/kg)
Safety and Side Effects
Myopathy and rhabdomyolysis (monitor CPK levels), eosinophilic pneumonia (rare but serious), and injection site reactions. CPK should be monitored weekly; daptomycin should be discontinued if CPK >1000 U/L with symptoms. Peripheral neuropathy with prolonged use. Generally well-tolerated compared to vancomycin.
References
- Fowler, V.G., et al. (2006). Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. New England Journal of Medicine, 355, 653-665.
- Arbeit, R.D., et al. (2004). The safety and efficacy of daptomycin for the treatment of complicated skin and skin-structure infections. Clinical Infectious Diseases, 38, 1673-1681.
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