Daptomycin is contraindicated in pulmonary infections despite being highly effective for skin and bloodstream Staphylococcal infections because:
- A Daptomycin is rapidly metabolised by type II pneumocytes before reaching the alveolar epithelium
- B Daptomycin achieves poor lung tissue concentrations due to its large molecular size
- C Pulmonary surfactant (phosphatidylglycerol) binds and inactivates daptomycin in the alveolar space, preventing it from reaching bacteria ✓
- D Staphylococci in the lung develop rapid inducible resistance to daptomycin via sur/mprF mutations
Correct answer: C. Pulmonary surfactant (phosphatidylglycerol) binds and inactivates daptomycin in the alveolar space, preventing it from reaching bacteria
Explanation
Daptomycin's mechanism involves calcium-dependent insertion into bacterial membranes via its lipophilic tail, disrupting membrane potential. Lung surfactant contains high concentrations of phosphatidylglycerol, which directly binds and sequesters the daptomycin-calcium complex, preventing it from interacting with bacterial membranes. This inactivation by surfactant renders daptomycin ineffective for pneumonia despite adequate plasma levels. It remains highly effective for bacteraemia, endocarditis, and skin/soft tissue infections.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.