Cefiderocol Resistance in Acinetobacter baumannii: Roles of β-Lactamases, Siderophore Receptors, and Penicillin Binding Protein 3

Antimicrob Agents Chemother. 2020 Oct 20;64(11):e01221-20. doi: 10.1128/AAC.01221-20. Print 2020 Oct 20.

Abstract

Cefiderocol is a siderophore cephalosporin active against many multidrug-resistant (MDR) Gram-negative pathogens. We examined the resistance mechanisms in 12 Acinetobacter baumannii strains with cefiderocol MICs ranging from ≤0.03 to >32 μg/ml. Cefiderocol resistance could not be explained by β-lactamase activity. Cefiderocol resistance was associated with reduced expression of the siderophore receptor gene pirA Mutations involving PBP3 may have contributed to resistance in one strain. Additional studies are needed to assess the role of other siderophore receptors.

Keywords: Acinetobacter; siderophore.

MeSH terms

  • Acinetobacter baumannii* / genetics
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Outer Membrane Proteins
  • Cefiderocol
  • Cephalosporins / pharmacology
  • Drug Resistance, Multiple, Bacterial / genetics
  • Gram-Negative Bacteria
  • Penicillin-Binding Proteins / genetics
  • Receptors, Cell Surface
  • beta-Lactamases / genetics
  • beta-Lactamases / pharmacology

Substances

  • Anti-Bacterial Agents
  • Bacterial Outer Membrane Proteins
  • Cephalosporins
  • Penicillin-Binding Proteins
  • Receptors, Cell Surface
  • siderophore receptors
  • beta-Lactamases