Daptomycin (lipopeptide): typically used for VRE and MRSA, but has had poor efficacy in clinical trials for CAP.
Proposed rationale: Daptomycin inserts into the membrane of gram-positive bacteria and artificial lipid vesicles. In the lungs, Daptomycin will insert into the lipid surfactant layer (which is abundant) due to lack of targeted specificity for the anti-microbial pathogens. Hence it will be effectively sequestrated and rendered inactive by pulmonary surfactant.
Silverman JA, Mortin LI, Vanpraagh AD, et al. Inhibition of daptomycin by pulmonary surfactant: in vitro modeling and clinical impact. J Infect Dis 2005;191:2149-52