Molecular mechanisms and clonal distribution of cefiderocol-resistant blaNDM-carrying Escherichia coli: a multi-centre study in China - PubMed

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Cefiderocol resistance is increasing globally, including in China, despite its unavailability there.
blaNDM-carrying Escherichia coli is a major pathogen causing cefiderocol resistance, with a resistance rate of 50.5% in the study.
High-level resistance is due to multiple mechanisms, including blaNDM production and CirA-frameshift mutation/PBP3 insertion.
No additional fitness cost was observed in CirA/PBP3 mutants.
20 homologous strains were identified, indicating possible clonal transmission and hospital outbreaks.
Resistance-related mutations (CirA-frameshift mutations/I547F and PBP3-Q227H, YRIN333ins, E349K, I532L) were co-occurring and concentrated in certain lineages.
Diverse sources suggest potential spread of resistant strains among humans, animals, and the environment.
Genetic distribution of resistant isolates is associated with their geographical origins.
The study highlights the need for a 'One Health' strategy to address cefiderocol resistance.

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