Distinct Subpopulations of Intravalvular Methicillin-Resistant Staphylococcus aureus With Variable Susceptibility to Daptomycin in Tricuspid Valve Endocarditis.

We present a case of endocarditis wherein organisms cultured from different valve leaflets yielded different daptomycin susceptibility from each other, and from organisms obtained from peripheral blood culture. Genomic analyses showed mutations in mprF, purR and agrA. Pharmacokinetic simulations showed consistent activity of daptomycin+beta-lactam against all subpopulations. This represents an opportunity to understand S. aureus evolution and fitness in vivo on daptomycin therapy, and the role of beta-lactams to prevent selection of daptomycin resistant subpopulations.