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Journal of Clinical Microbiology, January 2008, p. 220-224, Vol. 46, No. 1
0095-1137/08/$08.00+0     doi:10.1128/JCM.00660-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Evaluation of Endocarditis Caused by Methicillin-Susceptible Staphylococcus aureus Developing Nonsusceptibility to Daptomycin

Division of Infectious Diseases, New York Medical College and Westchester Medical Center, Valhalla, New York,¹ Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan,² Department of Medicine, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts,³ Department of Infectious Disease, Cleveland Clinic Foundation, Cleveland, Ohio,⁴ Cubist Pharmaceuticals, Lexington, Massachusetts⁵

Received 24 March 2007/ Returned for modification 23 July 2007/ Accepted 29 October 2007

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.

Published ahead of print on 14 November 2007.

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