Journal
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
Volume 72, Issue 6, Pages 1714-1722Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jac/dkx016
Keywords
-
Funding
- Novartis Medical School Grant (Basel, Switzerland)
- Spanish Network for Research in Infectious Diseases
- 'Emili Letang' Post-residency Scholarship from Hospital Clinic, Barcelona (Spain)
- Instituto de Salud Carlos III [CM14/00135]
- Ministerio de Economia and Competitividad, Madrid (Spain)
- Instituto de Salud Carlos III, Madrid, Spain [INT15/00168]
- European Regional Development Fund (ERDF) 'A way to build Europe'
- [REIPI RD06/0008]
Ask authors/readers for more resources
Background: Previous studies showed development of daptomycin non-susceptibility (DNS: MIC >4 mg/L) in Enterococcus faecalis infections. However, no studies have assessed the efficacy of the combination of daptomycin/ampicillin against E. faecalis strains developing DNS in the experimental endocarditis (EE) model. Objectives: To assess the in vitro and in vivo efficacy of daptomycin at 10 mg/kg/day, daptomycin/ampicillin and ampicillin/ceftriaxone against two high-level aminoglycoside-resistant E. faecalis strains, one developing DNS after in vitro exposure to daptomycin and another that did not (DS). Methods: Subculture of 82 E. faecalis strains from patients with endocarditis with daptomycin MICs, time-kill and in vivo experiments using the EE model. Results: 33% of the strains (27 of 82) displayed DNS after subculture with daptomycin. Daptomycin MIC rose from 0.5-2 to 8-16 mg/L. In time-kill experiments, when using a high inoculum (10(8) cfu/mL), daptomycin/ampicillin was synergistic for one-third of DS strains and none of DNS strains, while ampicillin/ceftriaxone retained synergy in all cases. In the EE model, daptomycin did not significantly reduce cfu/g from vegetations compared with control against either strain, while daptomycin/ampicillin reduced significantly more cfu/g than daptomycin against the DS strain, but not against the DNS strain [2.9 (2.0-4.1) versus 6.1 (4.5-8.0); P = 0.002]. Ampicillin/ceftriaxone was synergistic and bactericidal against both strains, displaying the same activity as daptomycin/ampicillin against the DS strain. Conclusions: Performance of an Etest for daptomycin MIC after subculture with daptomycin inhibitory doses on strains of high-level aminoglycoside-resistant E. faecalis endocarditis may be an easy test to predict the in vivo efficacy of daptomycin/ampicillin.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available