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The acquisition of transferable extrachromosomal fec operon is associated with a cefiderocol MIC increase in

Kaan Kocer1, Sébastien Boutin1,2,3, Klaus Heeg1

  • 1Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, Im Neuenheimer Feld 324, Heidelberg 69120, Germany.

The Journal of Antimicrobial Chemotherapy
|October 17, 2022
PubMed
Abstract

Insights

A transferable cefiderocol resistance determinant, the fec operon, was identified in multidrug-resistant Gram-negative bacteria. This mobile genetic element confers cefiderocol resistance, raising concerns about its spread.

Area of Science:

  • Microbiology
  • Genetics
  • Infectious Diseases

Background:

  • Cefiderocol is a novel cephalosporin effective against multidrug-resistant Gram-negative bacteria, including those with MBLs.
  • The emergence of cefiderocol resistance in blaVIM-carrying Enterobacterales suggests a transferable resistance mechanism beyond blaVIM.

Purpose of the Study:

  • To investigate the mechanism and transferability of cefiderocol resistance in MDR Gram-negative bacilli.
  • To identify novel transferable resistance determinants against cefiderocol.

Main Methods:

  • Liquid mating experiments were used to assess the transfer of mobile genetic elements.
  • Whole-genome sequencing (WGS) and quantitative RT-PCR were employed to identify and quantify resistance determinants and gene expression.
  • Transformation experiments validated the role of identified genetic elements in cefiderocol resistance.

Main Results:

  • A transferable accessory fec operon (fecABCDEIR) was identified and transferred via liquid mating.
  • Transformation of the fec operon into E. coli elevated cefiderocol MIC by at least 16-fold.
  • The fec operon confers broad-host-range cefiderocol resistance in E. coli and Pseudomonas aeruginosa.

Conclusions:

  • A novel, transferable cefiderocol resistance determinant, the accessory fec operon, has been identified.
  • The emergence and potential spread of this mobile resistance element warrant close monitoring.

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