Abstract
Carbapenem-resistant Escherichia coli (CREC) has emerged as a critical global health concern, particularly strains carrying the bla (NDM-5)-IncX3 plasmid. In this review, we synthesize recent advances in the molecular epidemiology, resistance mechanisms especially the transmission dynamics of the bla (NDM-5)-IncX3 plasmid, virulence factors, research methodologies, and current strategies for the prevention and control of CREC. We further explore the cross-species dissemination and adaptive evolution of bla (NDM-5)-IncX3 plasmids within the interconnected human-animal-environment interface. Based on these insights, we propose a novel triadic transmission model-"structural adaptation, host reciprocity, and environmental driving", alongside a One Health-based, multidimensional intervention framework spanning clinical, agricultural, and environmental domains. This review provides critical perspectives for the containment of carbapenem-resistant Enterobacteriaceae, offers theoretical support for anti-infective clinical practice, informs evidence-based public health policy, and facilitates the implementation of the One Health approach in antimicrobial resistance (AMR) governance.