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

Shazad Mushtaq, Zahra Sadouki, Anna Vickers, David Livermore, Neil Woodford

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6 Citations (Scopus)
26 Downloads (Pure)

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.
Original languageEnglish
Article numbere01582-20
JournalAntimicrobial Agents and Chemotherapy
Volume64
Issue number12
Early online date21 Sep 2020
DOIs
Publication statusPublished - Dec 2020

Keywords

  • Acinetobacter baumannii
  • Antimicrobial activity
  • Antimicrobial resistance
  • Carbapenamase
  • Cefiderocol
  • Enterobacterales
  • Enterobacteriaceae
  • Multidrug resistance
  • NDM
  • Pseudomonas aeruginosa

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