A patient with MRSA bacteraemia fails vancomycin therapy. Daptomycin is considered next. Daptomycin's bactericidal mechanism involves:
- A Inhibiting peptidoglycan cross-linking at the D-Ala-D-Lac terminus acquired by VRSA
- B Inserting into the gram-positive bacterial cytoplasmic membrane in a calcium-dependent manner, forming oligomeric pores that cause rapid K+ efflux and membrane depolarisation ✓
- C Covalently binding 23S rRNA at the A-site preventing amino-acyl tRNA entry
- D Inhibiting cell membrane ergosterol synthesis via 14-alpha-demethylase inhibition
Explanation
Daptomycin is a cyclic lipopeptide whose fatty acid tail inserts into the gram-positive cytoplasmic membrane in a calcium-dependent manner (calcium ions mediate oligomerisation and membrane anchoring). The insertion creates ion-selective pores causing K+ efflux, rapid membrane depolarisation, loss of membrane potential and inhibition of DNA/RNA/protein synthesis — leading to rapid bactericidal killing without cell lysis. It cannot penetrate the gram-negative outer membrane, limiting its spectrum. The D-Ala-D-Lac mechanism is how VRSA modifies its cell wall; ergosterol demethylation is targeted by azole antifungals.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.