In vitro activity of cefiderocol, a siderophore-cephalosporin, against multidrug-resistant gram-negative bacteria

Mushtaq, Shazad, Sadouki, Zahra, Vickers, Anna, Livermore, David and Woodford, Neil (2020) In vitro activity of cefiderocol, a siderophore-cephalosporin, against multidrug-resistant gram-negative bacteria. Antimicrobial Agents and Chemotherapy, 64 (12). ISSN 0066-4804

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Abstract

Cefiderocol is a parenteral siderophore cephalosporin, with a catechol-containing 3′ substituent. We evaluated its MICs against gram-negative bacteria, using iron-depleted Mueller-Hinton broth. The panel comprised 305 Enterobacterales, 111 P. aeruginosa and 99 A. baumannii, all selected for carbapenem resistance and multi-resistance to other agents. At 2 and 4 μg/ml cefiderocol inhibited 78.7% and 92.1% respectively of all Enterobacterales tested, with rates of 80-100% for isolates with all modes of carbapenem resistance except NDM enzymes (41.0% inhibited at 2 μg/ml, 72.1% at 4 μg/ml) or combinations of ESBL and porin-loss (61.5% inhibited at 2 μg/ml, 88.5% at 4 μg/ml). Cefiderocol also inhibited 81.1% and 86.5% of all P. aeruginosa at 2 and 4 μg/ml respectively, with rates of 80-100% for isolates with VIM, IMP, GES or VEB β-lactamases and slightly lower rates for those with NDM (45.5% at 2 μg/ml and 72.7% at 4 μg/ml) and PER (66.7% at 2 μg/ml and 73.3% at 4 μg/ml) enzymes; 63.3% of P. aeruginosa were inhibited at the FDA's 1 μg/ml breakpoint. Lastly, cefiderocol 2 and 4 μg/ml inhibited 80.8% and 88.9% of the A. baumannii isolates respectively, with rates >85% for isolates with OXA-51-like, -23, -24, or -58 enzymes and 50% at 2 μg/ml and 80% at 4 μg/ml for those with NDM carbapenemases. Dipicolinic acid and avibactam weakly potentiated cefiderocol against Enterobacterales with MBLs and serine carbapenemase respectively, indicating incomplete β-lactamase stability.

Item Type: Article
Uncontrolled Keywords: acinetobacter baumannii,antimicrobial activity,antimicrobial resistance,carbapenamase,cefiderocol,enterobacterales,enterobacteriaceae,multidrug resistance,ndm,pseudomonas aeruginosa,pharmacology,pharmacology (medical),infectious diseases ,/dk/atira/pure/subjectarea/asjc/3000/3004
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 03 Sep 2020 23:57
Last Modified: 06 Apr 2021 01:58
URI: https://ueaeprints.uea.ac.uk/id/eprint/76763
DOI: 10.1128/AAC.01582-20

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