title: Evaluation of endocarditis caused by methicillin-susceptible Staphylococcus aureus developing nonsusceptibility to daptomycin.
abstract: We examined sequential methicillin-susceptible Staphylococcus aureus isolates from a patient with mitral valve endocarditis recovered during persistent bacteremia on standard therapy and relapse after treatment with daptomycin. An isolate obtained after 5 days of antimicrobial therapy, but before exposure to daptomycin, showed subtle physiological changes in response to daptomycin, with significant regrowth in the daptomycin killing assay compared to the treatment-naive strain. Once daptomycin was started, the population became more heterogeneous and tested as nonsusceptible. These organisms were examined in a simulated-vegetation in vitro pharmacodynamic model, which confirmed progressive decreases in killing with daptomycin concentrations that simulate those attained in humans with 6-mg/kg of body weight daily dosing. Early surgical intervention or combination therapy or both might have prevented the loss of daptomycin susceptibility.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, New York Medical College, Munger Pavilion, Room 245, Valhalla, NY 10595, USA. george_sakoulas@nymc.edu
authors.forename: George
authors.initials: G
authors.lastname: Sakoulas
authors.forename: Warren
authors.initials: W
authors.lastname: Rose
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rybak
authors.forename: Satish
authors.initials: S
authors.lastname: Pillai
authors.forename: Jeff
authors.initials: J
authors.lastname: Alder
authors.forename: Robert C
authors.initials: RC
authors.lastname: Moellering
authors.forename: George M
authors.initials: GM
authors.lastname: Eliopoulos
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D016470:Bacteremia / Q000382:microbiology; D017576:Daptomycin / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D024881:Drug Resistance, Bacterial; D004697:Endocarditis, Bacterial / Q000382:microbiology*; D006801:Humans; D008297:Male; D008712:Methicillin / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000145:classification / Q000187:drug effects* / Q000302:isolation & purification
chemical_list: D000900:Anti-Bacterial Agents; D017576:Daptomycin; D008712:Methicillin