Merck Manual

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Brian J. Werth

, PharmD, University of Washington School of Pharmacy

Last full review/revision May 2020| Content last modified May 2020
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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 potassium 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

Daptomycin is used mainly for infections caused by

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

Animal reproduction studies with daptomycin have not shown risk to the fetus, and data related to pregnancy in humans are limited to case reports. The extent to which daptomycin crosses the placenta is unknown. Depending on the indication and the severity of illness, using daptomycin during pregnancy may be reasonable.

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

Adverse Effects

Adverse effects of daptomycin include

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-a-day dosing.

Dosing Considerations

Daptomycin is given parenterally once a 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.

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