Journal article
1,2,4-Oxadiazole antimicrobials act synergistically with daptomycin and display rapid kill kinetics against MDR Enterococcus faecium
Journal of Antimicrobial Chemotherapy, Vol.73(6), pp.1562-1569
2018
Abstract
Background: Enterococcus faecium is an important nosocomial pathogen. It has a high propensity for horizontal gene transfer, which has resulted in the emergence of MDR strains that are difficult to treat. The most notorious of these, vancomycin-resistant E. faecium, are usually treated with linezolid or daptomycin. Resistance has, however, been reported, meaning that new therapeutics are urgently needed. The 1,2,4-oxadiazoles are a recently discovered family of antimicrobials that are active against Gram-positive pathogens and therefore have therapeutic potential for treating E. faecium. However, only limited data are available on the activity of these antimicrobials against E. faecium.
Objectives: To determine whether the 1,2,4-oxadiazole antimicrobials are active against MDR and daptomycinnon- susceptible E. faecium.
Methods: The activity of the 1,2,4-oxadiazole antimicrobials against vancomycin-susceptible, vancomycin-resistant and daptomycin-non-susceptible E. faecium was determined using susceptibility testing, time-kill assays and synergy assays. Toxicity was also evaluated against human cells by XTT and haemolysis assays.
Results: The 1,2,4-oxadiazoles are active against a range of MDR E. faecium, including isolates that display nonsusceptibility to vancomycin and daptomycin. This class of antimicrobial displays rapid bactericidal activity and demonstrates superior killing of E. faecium compared with daptomycin. Finally, the 1,2,4-oxadiazoles act synergistically with daptomycin against E. faecium, with subinhibitory concentrations reducing the MIC of daptomycin for non-susceptible isolates to a level below the clinical breakpoint.
Conclusions: The 1,2,4-oxadiazoles are active against MDR and daptomycin-non-susceptible E. faecium and hold great promise as future therapeutics for treating infections caused by these difficult-to-treat isolates.
Details
- Title
- 1,2,4-Oxadiazole antimicrobials act synergistically with daptomycin and display rapid kill kinetics against MDR Enterococcus faecium
- Authors/Creators
- G.P. Carter (Author/Creator) - Peter Doherty InstituteJ.R. Harjani (Author/Creator) - Monash UniversityL. Liu (Author/Creator)N.P. Pitcher (Author/Creator) - Monash UniversityY. Nong (Author/Creator) - Peter Doherty InstituteT.V. Riley (Author/Creator) - Edith Cowan UniversityD.A. Williamson (Author/Creator) - Peter Doherty InstituteT.P. Stinear (Author/Creator) - Peter Doherty InstituteJ.B. Baell (Author/Creator) - Nanjing Tech UniversityB.P. Howden (Author/Creator) - Peter Doherty Institute
- Publication Details
- Journal of Antimicrobial Chemotherapy, Vol.73(6), pp.1562-1569
- Publisher
- Oxford University Press
- Identifiers
- 991005543352607891
- Copyright
- © 2018 The Author(s)
- Murdoch Affiliation
- School of Veterinary and Life Sciences
- Language
- English
- Resource Type
- Journal article
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- Domestic collaboration
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- Citation topics
- 1 Clinical & Life Sciences
- 1.23 Antibiotics & Antimicrobials
- 1.23.173 MRSA and VRE
- Web Of Science research areas
- Infectious Diseases
- Microbiology
- Pharmacology & Pharmacy
- ESI research areas
- Pharmacology & Toxicology