Global geographic and genomic epidemiology analysis of carbapenem-resistant <i>Escherichia coli</i> carrying <i>bla</i> _NDM-9

Carbapenem-resistant <i>Escherichia coli</i> (CREC), particularly strains producing New Delhi metallo-β-lactamase-9 (NDM-9), pose a growing threat as agents of nosocomial infections. Despite their emergence since 2013, a comprehensive global phylogeographic and genetic characterization of <i>bla</i>_NDM-9-carrying CREC is lacking. Through 7 years (2018-2024) of surveillance of CREC strains in a tertiary hospital, we obtained seven <i>bla</i>_NDM-9-carrying CREC. Antimicrobial susceptibility testing, conjugative transfer experiments, whole-genome sequencing (WGS), and fitness analysis were performed. Publicly available genomes of <i>bla</i>_NDM-9-carrying CREC from NCBI (curated by July 2025) were integrated for global analysis. All seven <i>bla</i>_NDM-9-carrying CREC exhibited resistance to most antimicrobials tested, except colistin. WGS revealed diverse <i>bla</i>_NDM-9-carrying plasmid types (IncB/O/K/Z, IncHI2, IncFIB, and IncC) and sequence types of strains (ST156 predominant). Key mobile genetic elements IS<i>26</i> and IS<i>CR1</i> facilitated <i>bla</i>_NDM-9 dissemination. Plasmid structural analysis traced the evolution of the IncB/O/K/Z plasmid, revealing potential intra-hospital persistence and spread. Carriage of <i>bla</i>_NDM-9-carrying plasmid imposed a significant fitness cost. Global analysis (<i>n</i> = 203 isolates) demonstrated high genetic diversity (56 STs), with ST156 (20.1%) being the most prevalent. Spatially, isolates were concentrated in Asia (China: 85.2%). Primary isolation sources were humans (39.4%) and chickens (34.9%), with a notable shift toward human predominance since 2016. Our findings elucidate the critical role of specific mobile elements in transmission, highlight the significant burden in China, document a shift toward human-associated isolates, and identify ST156 as a globally prevalent lineage. We emphasized the necessity of intensified surveillance to track the dissemination of <i>bla</i>_NDM-9-carrying CREC.IMPORTANCEThis study provides the first integrative geographic and genomic epidemiology analysis of <i>bla</i>_NDM-9-carrying carbapenem-resistant <i>Escherichia coli</i> (CREC). Our 7-year surveillance and genomic analysis revealed critical insights into the genetic characteristics and transmission dynamics of CREC carrying <i>bla</i>_NDM-9. The identification of mobile genetic elements, such as IS<i>26</i> and IS<i>CR1</i>, underscores their role in the horizontal transfer of resistance genes, facilitating the spread of <i>bla</i>_NDM-9. Furthermore, given the high frequency of <i>bla</i>_NDM-9-carrying CREC in China and its likelihood of spreading clonally in hospitals, there is an immediate need to intensify surveillance efforts. Adopting a One Health perspective, our study highlights the interconnected antimicrobial resistance risks spanning human, animal, and environmental health domains, advocating for strengthened global phylogeographic and phylogenetic surveillance alongside clinical interventions to curb the spread of these high-risk epidemic clones.