Daptomycin

Daptomycin, developed as LY146032 and marketed as Cubicin, contains a fatty tail enabling insertion into bacterial membranes. Activity includes susceptible Gram-positive organisms such as MRSA and vancomycin-resistant enterococci. First US approval was in 2003.

In the presence of calcium, the lipid tail inserts into the Gram-positive membrane and molecules cluster into channels. Potassium and other ions escape, membrane electrical potential collapses and DNA/RNA/protein synthesis fails, producing rapid concentration-dependent killing without cell bursting. Lung surfactant inactivates the drug, preventing useful pneumonia treatment. In the pivotal bloodstream-infection study, it was non-inferior to standard therapy for S. aureus bacteremia/right-sided endocarditis, with less renal dysfunction.

Supporting references: non-inferior.

FDA approval began with complicated skin and skin-structure infection in 2003, followed by S. aureus bloodstream infection including right-sided infective endocarditis. Once-daily IV treatment is for susceptible organisms and the actual infection context. It is explicitly not used for pneumonia.

Supporting references: approved.

Reported effects include diarrhea, headache, dizziness, rash, abnormal liver tests, elevated CPK, urinary tract infection, hypotension and dyspnea. Myopathy and rare rhabdomyolysis require CPK monitoring, and clinicians may pause statins. Eosinophilic pneumonia is an uncommon drug reaction, distinct from its lack of efficacy in ordinary pneumonia. Peripheral neuropathy, severe hypersensitivity including DRESS and tubulointerstitial nephritis are additional serious concerns.