Daptomycin: how it works, uses and side effects

Daptomycin is used for certain complicated skin infections and bloodstream infections caused by Staphylococcus aureus. It also acts against some resistant Gram-positive bacteria. It is not suitable for treating pneumonia, however: a substance in the lungs inactivates the medicine.

What is daptomycin?

Daptomycin is an antibiotic in the cyclic lipopeptide class, available under the brand name Cubicin. It consists of a ring-shaped peptide with a fatty-acid component. This component allows the medicine to insert itself into bacterial cell membranes.

Daptomycin acts against Gram-positive bacteria, including resistant organisms such as MRSA and vancomycin-resistant enterococci. It can therefore be a treatment option when first-choice medicines fail. It was developed under the name LY146032 and received US approval in 2003.

How does daptomycin work?

Daptomycin attacks bacterial cell membranes rather than cell walls. In the presence of calcium, its fatty-acid component inserts into the membrane of Gram-positive bacteria. A simplified account of what follows is that several drug molecules join together and form channels, allowing potassium and other ions to escape the cell. The electrical potential across the membrane rapidly collapses. Without it, the bacterium can no longer make DNA, RNA or proteins. It dies quickly without the cell bursting.

Daptomycin’s bacterial killing depends on its concentration. In the lungs, however, a particular substance limits its effect: pulmonary surfactant, a surface-active substance, inactivates daptomycin. It is therefore unsuitable for treating pneumonia.

A pivotal trial studied daptomycin in S. aureus bacteremia and right-sided endocarditis. Bacteremia means bacteria are present in the blood; right-sided endocarditis is inflammation of the inner lining of the right side of the heart. In this trial, daptomycin was noninferior to standard treatment. Kidney dysfunction also occurred less often with daptomycin. 1

Is daptomycin FDA-approved?

Yes. The US Food and Drug Administration approved daptomycin in 2003 for complicated skin and skin structure infections. Approval was later expanded to S. aureus bloodstream infections, including right-sided endocarditis. Daptomycin is administered intravenously, through a vein, usually once a day. 2

What is daptomycin prescribed for?

Daptomycin is prescribed for complicated skin and skin structure infections and S. aureus bloodstream infections, including right-sided infective endocarditis. The Gram-positive bacteria causing the infection must be susceptible to daptomycin for the medicine to act against them. It is not used for pneumonia.

What side effects can occur?

The prescribing information lists the following among the common side effects:

• Diarrhea, headache and dizziness
• Rash
• Abnormal liver tests and an increase in the muscle enzyme creatine phosphokinase (CPK)
• Urinary tract infections
• Low blood pressure and shortness of breath

Serious side effects can also occur. Some require specific monitoring during treatment:

• Muscle injury, or myopathy, and rarely the breakdown of muscle tissue, or rhabdomyolysis. CPK levels are therefore monitored. Statins may be paused during treatment when appropriate.
• Eosinophilic pneumonia, a less common inflammatory reaction in the lungs
• Peripheral neuropathy, meaning damage to nerves outside the brain and spinal cord
• Severe allergic reactions, including the serious drug reaction known as DRESS
• Kidney inflammation called tubulointerstitial nephritis