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By Hans P. Schlecht, MD, MSc, Assistant Professor of Medicine, Department of Medicine, Division of Infectious Diseases & HIV Medicine, Drexel University College of Medicine
Christopher Bruno, MD, Assistant Professor of Medicine, Division of infectious Diseases & HIV Medicine, Drexel University College of Medicine

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Daptomycin is a cyclic lipopeptide antibiotic that has a unique mechanism of action. It binds to the bacterial cell membranes, causing rapid depolarization of the membrane due to K efflux and associated disruption of DNA, RNA, and protein synthesis; the result is rapid concentration-dependent bacterial death (see Effectiveness).


Daptomycin has activity against the following:

  • Gram-positive bacteria (broad-spectrum activity)

  • Multidrug-resistant gram-positive bacteria (because cross-resistance with other classes of antibiotics does not occur)

Daptomycin is used mainly for infections caused by

  • Vancomycin- and methicillin-resistant Staphylococcus aureus

  • Vancomycin-resistant enterococci

  • Pneumococci with reduced penicillin sensitivity

However, methicillin-resistant S. aureus and vancomycin-resistant enterococci may become resistant during daptomycin therapy, resulting in relapsing or persistent infection.

Daptomycin is inferior to ceftriaxone for pneumonia, presumably because daptomycin can bind to pulmonary surfactant, reducing daptomycin’s activity in the alveolar epithelial lining fluid.


Daptomycin is contraindicated in patients who have had an allergic reaction to it.

Use During Pregnancy and Breastfeeding

Daptomycin is in pregnancy category B (animal studies show no risk and human evidence is incomplete).

Daptomycin enters breast milk, but oral availability is low; effects on breastfeeding infants are unknown.

Adverse Effects

Adverse effects include

  • Eosinophilic pneumonia

  • Myopathy

Chronic use may cause reversible organizing pneumonia with eosinophilic pulmonary infiltrates, presumably because daptomycin binds to pulmonary surfactant and thus accumulates in the alveolar spaces.

Skeletal myopathy due to daptomycin is reversible but seldom occurs with once/day dosing.

Dosing Considerations

Daptomycin is given parenterally once/day. Over 90% is bound to serum protein.

Dosing is adjusted for renal failure.

Because daptomycin can cause reversible skeletal myopathy, patients should be monitored for muscle pain or weakness, and serum creatine kinase levels should be checked weekly.