daptomycin

Daptomycin is a cyclic lipopeptide antibiotic produced by Streptomyces roseosporus. It is a bactericidal agent that binds to bacterial cell membranes in a calcium-dependent manner, causing rapid depolarization and inhibition of protein, DNA, and RNA synthesis, which leads to cell death.

The antibiotic has activity primarily against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus aureus, streptococci, and vancomycin-resistant enterococci (VRE). It is not active against most Gram-negative organisms and is inactivated by pulmonary surfactant, so it is not effective for pneumonia.

Indications in the United States include complicated skin and skin structure infections and Staphylococcus aureus bacteremia, including right-sided infective endocarditis. Daptomycin is administered intravenously; typical dosing ranges from 4-6 mg/kg once daily for complicated skin infections and 6-8 mg/kg once daily for bacteremia or right-sided endocarditis, with dose adjustments for renal impairment.

Pharmacokinetics and administration: the drug is primarily renally excreted with minimal hepatic metabolism. It is given by IV infusion, usually over about 30 minutes. Dose and frequency may be adjusted based on kidney function.

Adverse effects and monitoring: the most notable risk is myopathy and rhabdomyolysis, particularly when used with statins; monitoring of creatine kinase is recommended during therapy. Other adverse effects include eosinophilic pneumonia (rare) and injection-site reactions.

Resistance remains uncommon but has been reported and is generally linked to changes in the bacterial cell membrane that reduce daptomycin binding, such as mutations affecting membrane charge or composition.

Regulatory status: approved for complicated skin infections and for Staphylococcus aureus bacteremia, including right-sided infective endocarditis.