Daptomycin's mechanism of action makes it the only antibiotic to be bactericidal in a calcium-dependent manner. This mechanism is:

• A It chelates calcium in the bacterial cell wall, destabilizing peptidoglycan
• B Calcium-dependent insertion into gram-positive bacterial membrane, forming oligomeric pores that depolarize membrane potential and cause rapid potassium efflux and cell death ✓
• C Calcium-dependent activation of daptomycin as a prodrug by bacterial enzymes
• D Competitive inhibition of D-Ala-D-Lac ligase (VanA) active only in the presence of calcium

Explanation

Daptomycin is a cyclic lipopeptide antibiotic that, in the presence of physiological calcium concentrations (which neutralize its anionic charge and allow membrane insertion), forms oligomeric structures that insert into the gram-positive cytoplasmic membrane. These pores cause rapid depolarization of membrane potential via potassium ion efflux, halting multiple essential functions simultaneously — DNA, RNA, and protein synthesis — killing the cell rapidly without cell lysis. It is specifically inactivated in lung surfactant (phosphatidylglycerol-rich), explaining why it cannot be used for pneumonia despite being active against S. pneumoniae in vitro.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.