In this episode of Real Life Pharmacology, we take a deep dive into daptomycin, a lipopeptide antibiotic primarily used for serious Gram-positive infections, including MRSA and VRE. Daptomycin works by binding to bacterial cell membranes in a calcium-dependent manner, causing rapid depolarization and cell death.
One key limitation is that daptomycin should never be used for pneumonia because pulmonary surfactant inactivates the drug. Clinically, it’s often reserved for bacteremia, endocarditis, or complicated skin and soft tissue infections.
From a pharmacokinetic standpoint, daptomycin is given intravenously and primarily eliminated unchanged by the kidneys, so dose adjustments are necessary in renal impairment. 
Monitoring creatine kinase (CK) levels is crucial, as one of the major adverse effects is myopathy and, rarely, rhabdomyolysis. Patients on statins have a higher risk of muscle toxicity, and clinicians should consider holding or monitoring statin therapy closely. 
Eosinophilic pneumonia is another rare but serious adverse reaction that can develop after prolonged therapy. Daptomycin has minimal drug interactions, making it an appealing option when other agents pose risks. Overall, it’s a powerful antibiotic when used appropriately, but requires careful monitoring for muscle and respiratory-related side effects.
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