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

Razieh Kebriaei; Seth A. Rice; Kavindra V. Singh; Kyle C. Stamper; An Q. Dinh; Rafael Rios; Lorena Diaz; Barbara E. Murray; MUNITA SEPULVEDA, JOSE MANUEL; Truc T. Tran; Cesar A. Arias; Michael J. Rybak

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

Journal

Antimicrobial Agents and Chemotherapy

ISSN

0066-4804

1098-6596

Date Issued

2018

Author(s)

Razieh Kebriaei

Seth A. Rice

Kavindra V. Singh

Kyle C. Stamper

An Q. Dinh

Rafael Rios

Lorena Diaz

Barbara E. Murray

MUNITA SEPULVEDA, JOSE MANUEL

Facultad de Medicina Clínica Alemana Universidad del Desarrollo

Truc T. Tran

Cesar A. Arias

Michael J. Rybak

Type

Resource Types::text::journal::journal article

DOI

10.1128/AAC.00315-18

URL

https://investigadores.udd.cl/handle/123456789/2666

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).