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
Truc T. Tran
Cesar A. Arias
Michael J. Rybak
Type
Resource Types::text::journal::journal article
Abstract
<jats:p>
<jats:named-content content-type="genus-species">Enterococcus faecium</jats:named-content>
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
<jats:named-content content-type="genus-species">E. faecium</jats:named-content>
HOU503, a DAP-susceptible strain that harbors common LiaS and LiaR substitutions found in clinical isolates (T120S and W73C, respectively).
</jats:p>
<jats:named-content content-type="genus-species">Enterococcus faecium</jats:named-content>
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
<jats:named-content content-type="genus-species">E. faecium</jats:named-content>
HOU503, a DAP-susceptible strain that harbors common LiaS and LiaR substitutions found in clinical isolates (T120S and W73C, respectively).
</jats:p>
Subjects
combination therapy
;
daptomycin
;
pk/pd
;
vrefm