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 susceptibilities from each other and from organisms obtained from peripheral blood culture. Genomic analyses showed mutations in , and Pharmacokinetic simulations showed consistent...

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Published in:	Antimicrobial agents and chemotherapy Vol. 64; no. 3
Main Authors:	Miller, Christopher R, Dey, Somrita, Smolenski, Paula D, Kulkarni, Pushkar S, Monk, Jonathan M, Szubin, Richard, Sakoulas, George, Berti, Andrew D
Format:	Journal Article
Language:	English
Published:	United States American Society for Microbiology 21-02-2020
Subjects:	Aminoacyltransferases - genetics Bacterial Proteins - genetics Daptomycin - pharmacology Daptomycin - therapeutic use Endocarditis, Bacterial - drug therapy Endocarditis, Bacterial - genetics Endocarditis, Bacterial - microbiology Humans Mechanisms of Resistance Methicillin-Resistant Staphylococcus aureus - drug effects Methicillin-Resistant Staphylococcus aureus - genetics Microbial Sensitivity Tests Mutation - genetics Repressor Proteins - genetics Tricuspid Valve - drug effects Tricuspid Valve - microbiology Tricuspid Valve - pathology Whole Genome Sequencing combination therapy daptomycin endocarditis agr fitness MRSA
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Summary:	We present a case of endocarditis wherein organisms cultured from different valve leaflets yielded different daptomycin susceptibilities from each other and from organisms obtained from peripheral blood culture. Genomic analyses showed mutations in , and Pharmacokinetic simulations showed consistent activity of daptomycin plus beta-lactam against all subpopulations. This represents an opportunity to understand evolution and fitness on daptomycin therapy and the role of beta-lactams to prevent the selection of daptomycin-resistant subpopulations.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Citation Miller CR, Dey S, Smolenski PD, Kulkarni PS, Monk JM, Szubin R, Sakoulas G, Berti AD. 2020. Distinct subpopulations of intravalvular methicillin-resistant Staphylococcus aureus with variable susceptibility to daptomycin in tricuspid valve endocarditis. Antimicrob Agents Chemother 64:e01593-19. https://doi.org/10.1128/AAC.01593-19.
ISSN:	0066-4804 1098-6596
DOI:	10.1128/AAC.01593-19