Impact of extended-spectrum chromosomal AmpC (ESAC) of Escherichia coli on susceptibility to cefiderocol

TL;DR

This study shows that certain enzymes in Escherichia coli can reduce the effectiveness of the antibiotic cefiderocol, in addition to other drugs.

Contribution

The study reveals that extended-spectrum AmpC enzymes in E. coli can also break down cefiderocol, a previously thought-resistant antibiotic.

Findings

ESAC enzymes confer resistance to ceftazidime and decreased susceptibility to cefepime.

Cefiderocol is also a substrate for ESAC enzymes, reducing its effectiveness.

Susceptibility to cefiderocol is impacted by chromosomally encoded ESAC enzymes in E. coli.

Abstract

The impact of chromosomally encoded wild-type or extended-spectrum (ESAC) AmpC β-lactamases of Escherichia coli on susceptibility to ceftazidime, cefepime, and cefiderocol was evaluated in different genetic backgrounds, including wild-type, PBP3-modified, and porin-deficient E. coli strains. Recombinant E. coli strains possessing the different backgrounds and producing variable ESACs were evaluated. Although ESAC enzymes conferred resistance to ceftazidime and decreased susceptibility to cefepime as expected, we showed here that cefiderocol was also a substrate of ESAC enzymes.

We showed here that chromosomally encoded intrinsic extended-spectrum cephalosporinases of Escherichia coli may impact susceptibility not only to ceftazidime and cefepime but also to cefiderocol.