Daptomycin Flashcards
What is the mechanism of action of daptomycin?
Daptomycin is a lipopeptide antibiotic that inserts into Gram-positive bacterial cell membranes, causing rapid depolarization by forming ion-conducting channels. This loss of membrane potential inhibits DNA, RNA, and protein synthesis, leading to bactericidal action.
Describe the spectrum of activity of daptomycin.
Daptomycin is active only against Gram-positive organisms. It covers MRSA, MSSA, Enterococci (including many VRE strains), and other resistant Gram-positives. It has no activity against Gram-negative bacteria and is ineffective in the lung due to inactivation by surfactant.
How might bacteria develop resistance to daptomycin?
Resistance is uncommon but can occur via changes in the cell membrane, such as thickened cell wall or altered membrane phospholipids reducing daptomycin binding. Some strains of enterococci develop mutations that increase the repulsion of the positively charged daptomycin molecule.
Outline key pharmacokinetic features of daptomycin.
Daptomycin is given IV (no oral form), is highly protein-bound, and has a relatively long half-life (~8 hours, allowing once-daily dosing). It’s primarily eliminated by the kidneys and does not penetrate the CSF or lungs effectively.
What significant drug interactions does daptomycin have?
Daptomycin’s major interaction is with HMG-CoA reductase inhibitors (statins): co-administration can increase the risk of muscle toxicity. It doesn’t significantly affect cytochrome P450 enzymes.
What are the main clinical indications for daptomycin?
Daptomycin is used for serious Gram-positive infections, especially those resistant to other agents, such as MRSA bacteremia and right-sided endocarditis, complicated skin and soft tissue infections by MRSA or VRE, and VRE bacteremia.
Since daptomycin is inactivated by surfactant, it should NOT be used for pneumonia.
When is daptomycin contraindicated or to be used with caution?
Avoid daptomycin for pneumonia. Use with caution in patients on statins or with pre-existing muscle disorders due to risk of myopathy (leading to AKI and rhabdomyolysis). Adjust dose in renal dysfunction. Contraindicated in those with a known hypersensitivity to daptomycin.
List major adverse effects of daptomycin.
The primary toxicity is muscle injury: myopathy and rhabdomyolysis (monitor CPK levels weekly). Patients may experience muscle pain or weakness. It can also cause eosinophilic pneumonia (rare but serious). Other side effects include GI upset, headache, and injection site reactions.
Is there a mnemonic to remember daptomycin key points?
Remember ‘DAPto’: Depolarizes membrane, Avoid Pneumonia, Toxicity to muscles (myopathy), and Only Gram-positives.
