Global geographic and genomic epidemiology analysis of carbapenem-resistant Escherichia coli carrying bla NDM-9

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Carbapenem-resistant Escherichia coli (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 bla NDM-9 -carrying CREC is lacking. Through 7 years (2018–2024) of surveillance of CREC strains in a tertiary hospital, we obtained seven bla NDM-9 -carrying CREC. Antimicrobial susceptibility testing, conjugative transfer experiments, whole-genome sequencing (WGS), and fitness analysis were performed. Publicly available genomes of bla NDM-9 -carrying CREC from NCBI (curated by July 2025) were integrated for global analysis. All seven bla NDM-9 -carrying CREC exhibited resistance to most antimicrobials tested, except colistin. WGS revealed diverse bla 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 26 and IS CR1 facilitated bla 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 bla NDM-9 -carrying plasmid imposed a significant fitness cost. Global analysis ( n = 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 bla NDM-9 -carrying CREC. IMPORTANCE This study provides the first integrative geographic and genomic epidemiology analysis of bla NDM-9 -carrying carbapenem-resistant Escherichia coli (CREC). Our 7-year surveillance and genomic analysis revealed critical insights into the genetic characteristics and transmission dynamics of CREC carrying bla NDM-9 . The identification of mobile genetic elements, such as IS 26 and IS CR1 , underscores their role in the horizontal transfer of resistance genes, facilitating the spread of bla NDM-9 . Furthermore, given the high frequency of bla 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.