Why is daptomycin not used for pneumonia?

• A. It causes severe bronchospasm.
• B. It is rapidly degraded by alveolar fluid.
• C. It is inactivated by pulmonary surfactant; poor activity in the lungs.
• D. It has no activity against Gram-positive organisms.

Answer: (C)

Pulmonary surfactant inactivates daptomycin, so it can’t work effectively in the lung. Daptomycin kills Gram-positive bacteria by binding their membranes in a calcium-dependent way, causing rapid depolarization and cell death. But when it reaches the alveolar space, surfactant binds the drug and prevents it from interacting with bacterial membranes, leading to poor activity in the lungs. That’s why it’s not used for pneumonia, even though it’s active against Gram-positive organisms elsewhere in the body.