Genotypic-phenotypic discordance for cefiderocol against Enterobacter hormaechei

Area of Science:

• Microbiology
• Genomics
• Antimicrobial Resistance

Background:

• The Enterobacter cloacae complex (ECC) causes severe healthcare-associated infections with limited treatment options due to antimicrobial resistance.
• Cefiderocol is a key treatment for carbapenem-resistant pathogens, but treatment failures occur, especially with borderline minimum inhibitory concentrations (MICs).

Purpose of the Study:

• To characterize the genomic resistance landscape of a cefiderocol-susceptible Enterobacter hormaechei isolate.
• To investigate potential genomic-phenotypic discordance affecting cefiderocol activity.

Main Methods:

• Genomic and phenotypic characterization of a clinical Enterobacter hormaechei subsp. hoffmannii isolate.
• Whole-genome sequencing to identify resistance determinants and mutations.

Main Results:

• The isolate exhibited extensive resistance to multiple antibiotics but remained susceptible to cefiderocol (MIC=2 mg/L).
• Genomic analysis revealed blaNDM-1, mutations in iron uptake pathways, and alterations in global regulators and beta-lactam targets (ftsI).

Conclusions:

• Genomic-phenotypic discordance was observed in this E. hormaechei isolate with borderline cefiderocol susceptibility.
• MIC values alone may overestimate cefiderocol efficacy; genomic assessment is crucial for high-risk Enterobacterales.