Rapid selection of a cefiderocol-resistant Escherichia coli producing NDM-5 associated with a single amino acid substitution in the CirA siderophore receptor.

Abstract

Cefiderocol is a novel siderophore-conjugated cephalosporin that is very promising for the treatment of infections caused by MDR bacteria. Its main advantages reside in its stability against MBLs for which no other commercially β-lactam can be used to date, and its uptake using the bacterial iron transport system in addition of porins.1 However, its first clinical uses also revealed acquired resistance mechanisms in Enterobacterales.2–6 Here, we describe the in vivo selection of a cefiderocol-resistant Escherichia coli ST361 producing NDM-5 after a short exposure to the antibiotic. Two isolates (E. coli 308F7 and 308F8) isolated from blood samples from the same patient 15 days apart were sent to the French National Reference Center (NRC) for antimicrobial resistance for expertise. During this period, the patient had been treated with cefiderocol for 10 days (2 g × 3/day). A homemade Carba-NP test coupled with the lateral flow immunoassay NG-Test CARBA 5 assay (NG Biotech, Guipry, France) revealed the production of an NDM-like carbapenemase. MICs were determined by commercial lyophilized broth microdilution (BMD) plates (EUMDROXF Sensititre®, Thermo Scientific, Les Ulis, France), and interpreted using EUCAST guidelines. Both isolates exhibited the same phenotype with high resistance to all β-lactams. The first isolate (E. coli 308F7, accession number JANUGM000000000) was susceptible to cefiderocol (MIC = 2 mg/L) whereas the second isolate (308F8, accession number JANUGN000000000) was resistant (MIC > 8 mg/L, Table S1). Both isolates belonged to ST361, determined by the MLST v2.0 tool (https://cge.food.dtu.dk/services/MLST/).