Daptomycin

Eric Scholar University of Nebraska Medical Center, Omaha, United States

2009 Elsevier Inc. All rights reserved.

Introduction
Daptomycin is a member of a new class of antibiotics, the cyclic lipopeptides. It is derived
from Streptomyces roseosporus as a fermentation product. Daptomycin is a bactericidal
antibiotic and is active against aerobic, facultative, and anaerobic gram-positive bacteria.
It kills bacteria by interacting with bacterial membranes. It has been approved for the
intravenous treatment of complicated skin and skin structure infections and recently for
treating endocarditis and bacteremia caused by Staphylococcus aureus. It is an alternative to vancomycin for methicillin-resistant Stapylococcus aureus infections. GI disorders,
injection site reactions, fever, headache, insomnia, dizziness, and rash have occurred with
daptomycin.

Nomenclature
Name of the Clinical Form
Related Names Source: EMTREE
Chemical Names
CAS Number

Cidecin, Cubicin, Daptomycine, Daptomycinum,

Daptomicina, LY146032
103060-53-3

Basic Chemistry
Chemical Structure
Structure

Daptomycin

Comments
Chemical Formula
Properties
Physical Properties
Molecular Weight
Solubility

Structure from PubChem

C72H101N17O26

1620.670

Human Pharmacokinetics
Daptomycin is poorly absorbed orally and is only given intravenously. It shows linear
pharmacokinetics at doses up to 8 mg/kg. It is reversibly bound to albumin and has a
serum half life of 89 hours. Approximately 80% of the dose is recovered in the urine and
a small amount in the feces. Daptomycin is not metabolized by the liver and it neither
induces nor inhibits cytochrome isoenzymes and the drug has no important drugdrug
interactions Chambers (2006), Physicians Desk Reference Cubicin (2006).

Pharmacokinetic Properties

Value

Units

Prep. and
Route of
Admin.

Reference

Absorption

Comments
It is poorly
absorbed
orally and
is given by
i.v. injection.

Bioavailability
Distribution
Volume of Distribution

100

i.v.

0.104

L/kg

i.v.

Plasma Protein Binding

92

i.v.

Physicians Desk Reference

Cubicin (2006)
Physicians Desk Reference
Cubicin (2006)

Metabolism

Daptomycin
is not
metabolized
by the liver
and it neither
induces nor
inhibits
cytochrome
isoenzymes

Plasma Half-Life

8.9

Bio Half-Life
Clearance

4.4

ml/h/kg

i.v.

Physicians Desk Reference

Cubicin (2006)
Physicians Desk Reference
Cubicin (2006)

Daptomycin
Routes of Elimination

80% of the drug

is excreted
in the urine.
Dosage
adjustment
is necessary
in patients
with severe
renal insufficiency.

Targets-Pharmacodynamics
Daptomycin binds to the cell membrane via calcium-dependent insertion of its lipid tail,
forming an ion-conduction structure that is hypothesized to rapidly depolarize the cell
membrane via an efflux of potassium that is associated with a disruption of DNA, RNA
and protein synthesis and with cellular death Carpenter and Chambers (2004), Silverman
et al (2003), Chambers (2006).

Target Name(s):
Bacterial plasma membrane

Therapeutics
Daptomycin is a useful alternative to other agents (e.g., linezolid, quinupristin/dalfopristin) for treating infections caused by resistant gram-positive pathogens, including
methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. There
are few options at present for treating these infections. Daptomycin is indicated for the
treatment of complicated skin and skin structure infections and Staphylococcus aureus
bloodstream infections (bacteremia), including those with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates Carpenter and
Chambers (2004), Chambers (2006).

Indications

Value

Units

Prep. and
Route of
Admin.

Reference

Comments

Complicated skin and skin-structure infections caused by methicillin-susceptible and

methicillin-resistant strains of S. aureus, hemolytic streptococci, and
vancomycin-susceptible E.faecalis
Dosage
4
mg/kg
i.v. every 24 h
Carpenter and
Given over
Chambers (2004);
30 min
Medical Letter (2004)
Bacteremia and endocarditis caused by Staphylococcus aureus
Dosage
6
mg/kg
i.v. every 24 h
Fowler et al (2006)
Dosage

Daptomycin

Contraindications
Hypersensitivity to daptomycin

Adverse Effects
Among the more common adverse effects are GI disorders, injection site reactions, fever,
headache, insomnia, dizziness, and rash have occurred with daptomycin. In humans,
creatine kinase is elevated after high doses of the drug and there is a potential for
myopathy Physicians Desk Reference Cubicin (2006), Medical Letter (2004).

Pre-Clinical Research
Daptomycin shows rapid, concentration-dependent bactericidal activity in vitro
against Gram-positive organisms, including enterococci. It acts against most clinically
significant Gram-positive bacteria but not against Gram-negative bacteria. It is active
against antibiotic-resistant strains such as methicillin-resistant Staphylococcus aureus,
vancomycin-resistant enterococci and penicillin resistant Streptococcus pneumoniae.
Daptomycin has also been shown to be effective in several in vivo animal models of
bacterial infection of the soft tissues, bloodstream, kidneys, heart, lungs, and bone
including those caused by Gram-positive to standard therapies Tally and DeBruin (2000).

Other Information Web Sites

A PubChem Compound summary is available at http://pubchem.ncbi.nlm.nih.gov/
summary/summary.cgi?cid=6129688
http://www.thomsonhc.com/hcs/librarian/PFPUI/5x4T5aI11S27yJ Micromedex, 2006
http://www.cubicin.com/ Daptomycin web site

Journal Citations
Carpenter, C.F., Chambers, H.F., 2004. Daptomycin: Another novel agent for treating infections due to
drug-resistant gram-positive pathogens. Clin. Infect. Dis., 38, 9941000.
Medical Letter 2004 Daptomycin (Cubicin) for skin and soft tissue infections, 46, 1112.
Fowler, V.G., Boucher, H.W., Corey, R., Abrutyn, E., Karchmer, A.W., et al. 2006. Daptomycin versus
standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. New. Eng.
J. Med., 355, 653665.
Tally, F.P., DeBruin, M.F., 2000. Development of daptomycin for Gram-positive infections. J. Antimicrob.
Chemother., 46, 523526.
Silverman, J.A., Perlmutter, N.G., Shapiro, H.M., 2003. Correlation of daptomycin bactericidal activity and
membrane depolarization in Staphylococcus aureus. Antimicrob. Agents Chemother., 47, 25382544.

Book Citations
Chambers, H.F, 2006. Protein synthesis inhibitors and miscellaneous antibacterial agents. Bruton, L.L.,
Lazo, J.S., Parker, K.L. (Ed.), The Pharmacological Basis of Therapeutics, 11, pp. 11731202, McGraw
Hill, NY, NY.
Physicians Desk Reference (PDR) 2006 Cubicin (Daptomycin), 60th, pp. 1038104210381042.

Daptomycin

Further Reading
D. Greenwood. Miscellaneous antibacterial agents. In Antibiotic and Chemotherapy, 8th ed., Churchill
Livingstone, NY, 2003. p. 408.
Schriever, C. A. Fernandez, C., Rodvold, K. A. and Danziger, L.H., Daptomycin: A novel cyclic lipopeptide
antimicrobial, American Journal of Health System Pharmacy, 62 (2005) 11451158.