Influence of Inoculum Effect on the Efficacy of Daptomycin Monotherapy and in Combination with β-Lactams against Daptomycin-Susceptible Enterococcus faecium Harboring LiaSR Substitutions-Reference-Cited by-同舟云学术

Influence of Inoculum Effect on the Efficacy of Daptomycin Monotherapy and in Combination with β-Lactams against Daptomycin-Susceptible Enterococcus faecium Harboring LiaSR Substitutions

Published:2018-08 Issue:8 Volume:62 Page:
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Kebriaei Razieh¹,Rice Seth A.¹,Singh Kavindra V.²³,Stamper Kyle C.¹,Dinh An Q.²³,Rios Rafael⁴,Diaz Lorena³⁴,Murray Barbara E.²³,Munita Jose M.⁵⁶,Tran Truc T.²³,Arias Cesar A.²³⁷⁴,Rybak Michael J.¹⁸

Affiliation:

1. Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, Michigan, USA

2. Division of Infectious Diseases, UT Health McGovern Medical School, Houston, Texas, USA

3. Center for Antimicrobial Resistance and Microbial Genomics (CARMiG), UT Health McGovern Medical School, Houston, Texas, USA

4. Molecular Genetics and Antimicrobial Resistance Unit, International Center for Microbial Genomics, Universidad El Bosque, Bogotá, Colombia

5. Clinica Alemana, Santiago, Chile

6. Universidad del Desarrollo, Santiago, Chile

7. Center for Infectious Diseases, UT Health School of Public Health, Houston, Texas, USA

8. School of Medicine, Wayne State University, Detroit, Michigan, USA

Abstract

Enterococcus faecium isolates that harbor LiaFSR substitutions but are phenotypically susceptible to daptomycin (DAP) by current breakpoints are problematic, since predisposition to resistance may lead to therapeutic failure. Using a simulated endocardial vegetation (SEV) pharmacokinetic/pharmacodynamic (PK/PD) model, we investigated DAP regimens (6, 8, and 10 mg/kg of body weight/day) as monotherapy and in combination with ampicillin (AMP), ceftaroline (CPT), or ertapenem (ERT) against E. faecium HOU503, a DAP-susceptible strain that harbors common LiaS and LiaR substitutions found in clinical isolates (T120S and W73C, respectively).

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/AAC.00315-18

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