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Published on: July 9, 2012
Higher rates of cefiderocol resistance among NDM producing Klebsiella bloodstream isolates applying EUCAST over CLSI
Burcu Isler1,2, Cansel Vatansever3, Berna Özer3
1UQ Centre for Clinical Research, Faculty of Medicine, University of Queensland, Brisbane, Australia.
Background:
Cefiderocol is generally active against carbapenem-resistant Klebsiella spp. (CRK) with higher MICs against metallo-beta-lactamase producers. There is a variation in cefiderocol interpretive criteria determined by EUCAST and CLSI. Our objective was to test CRK isolates against cefiderocol and compare cefiderocol susceptibilities using EUCAST and CLSI interpretive criteria.
Methods:
A unique collection (n = 254) of mainly OXA-48-like- or NDM-producing CRK bloodstream isolates were tested against cefiderocol with disc diffusion (Mast Diagnostics, UK). Beta-lactam resistance genes and multilocus sequence types were identified using bioinformatics analyses on complete bacterial genomes.
Results:
Median cefiderocol inhibition zone diameter was 24 mm (interquartile range [IQR] 24-26 mm) for all isolates and 18 mm (IQR 15-21 mm) for NDM producers. We observed significant variability between cefiderocol susceptibilities using EUCAST and CLSI breakpoints, such that 26% and 2% of all isolates, and 81% and 12% of the NDM producers were resistant to cefiderocol using EUCAST and CLSI interpretive criteria, respectively.
Conclusions:
Cefiderocol resistance rates among NDM producers are high using EUCAST criteria. Breakpoint variability may have significant implications on patient outcomes. Until more clinical outcome data are available, we suggest using EUCAST interpretive criteria for cefiderocol susceptibility testing.
Insights
Cefiderocol shows variable activity against carbapenem-resistant Klebsiella spp. (CRK). EUCAST and CLSI criteria yield significantly different resistance rates, especially for NDM producers, impacting patient care.
Area of Science:
- Clinical microbiology
- Antimicrobial resistance
- Infectious diseases
Background:
- Cefiderocol demonstrates activity against carbapenem-resistant Klebsiella spp. (CRK).
- Higher minimum inhibitory concentrations (MICs) are observed for metallo-beta-lactamase (NDM) producers.
- Discrepancies exist in cefiderocol interpretive criteria between EUCAST and CLSI.
Purpose of the Study:
- To evaluate cefiderocol activity against CRK isolates.
- To compare cefiderocol susceptibility testing results using EUCAST and CLSI interpretive criteria.
Main Methods:
- Testing of 254 CRK bloodstream isolates against cefiderocol using disc diffusion.
- Identification of beta-lactam resistance genes and multilocus sequence types via whole-genome sequencing.
Main Results:
- Median cefiderocol zone diameter was 24 mm overall and 18 mm for NDM producers.
- EUCAST criteria classified 26% of isolates and 81% of NDM producers as resistant.
- CLSI criteria classified 2% of isolates and 12% of NDM producers as resistant.
Conclusions:
- High cefiderocol resistance rates among NDM producers are noted with EUCAST criteria.
- Variability in breakpoints impacts clinical interpretation and patient outcomes.
- Recommends using EUCAST interpretive criteria for cefiderocol susceptibility testing pending further clinical data.
