Dynamics of extended spectrum cephalosporin and carbapenem resistance genes in Escherichia coli: An emerging environmental hazard.

Carbapenem- and cephalosporin-resistant Escherichia coli (CCREC) represent a growing global hazard, disseminating across human, animal and environmental reservoirs. We analysed 81,718 E. coli genomes, carrying key cephalosporin and carbapenem resistance genes, to characterise the global trends in resistance determinants and phylogenetic lineages. Further, spatiotemporal trends and international transmission dynamics, with time-scaled phylogenetic and ancestral state reconstruction was performed on a globally representative subset. The dataset spanned 1905 till 2024, covering 3169 Sequence Types (STs) and 84 countries. Three STs dominated globally: ST131 (phylogroup B2), ST10 (phylogroup A/B1), and ST410 (phylogroup C). ST131 expanded rapidly after 2008, peaking around 2020, and was strongly associated with human infections, while ST10 was enriched in animals and birds (χ² tests, p < 0.0001). Extended-Spectrum β-lactamase (ESBL) and carbapenemase trajectories showed steep rises, with blaCTX-M-15 significantly more prevalent in ST131 (χ² test, p < 0.0001). The blaCTX-M-15 was the most prevalent globally, while blaNDM-5 surpassed blaNDM-1 after 2010. The blaNDM-5 was majorly associated with ST167. Asia was dominant in blaNDM-5 and blaCTX-M-15/14/27/55, Europe exhibited high blaCTX-M-15/blaOXA-1/blaOXA-48 frequencies, and North America carried blaKPC and blaCMY-2. The ST131/B2 harboured higher virulence scores (median 31.0 [29.0-34.0]) than in ST10 (median 18.0 [14.0-26.0]). The E. coli lineage originated around 1263, with early dispersal from the USA to Europe. We identified 1482 transmission routes among 863 ST131 E. coli genomes, dominated by USA-Japan and USA-Canada links. This emphasizes the urgent need for One Health containment strategies to limit the spread of CCREC.