A 70-year-old man with MRSA bacteremia secondary to hospital-acquired pneumonia is considered for daptomycin. The infectious disease team rejects daptomycin for the pulmonary source despite an MIC within the susceptible range. The reason is:

• A Daptomycin is extensively bound by pulmonary surfactant, rendering it inactive in alveolar lining fluid ✓
• B Daptomycin achieves poor penetration into lung parenchyma because of its large volume of distribution
• C Pulmonary epithelial lining fluid contains calcium concentrations too low to activate daptomycin
• D Anaerobic conditions within consolidated lung abolish daptomycin's bactericidal action

Explanation

Daptomycin binds avidly to phospholipids in pulmonary surfactant, which sequesters the drug and abolishes its ability to insert into bacterial membranes. A landmark randomized trial showed inferiority versus standard therapy for S. aureus pneumonia, so daptomycin is contraindicated for pneumonia despite excellent blood levels. Lung penetration is adequate; the problem is functional inactivation at the alveolar surface. Its calcium-dependent membrane insertion still proceeds in vivo elsewhere, and it does not depend on aerobic metabolism.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.