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This study reveals the worldwide geographic spreading patterns and spatiotemporal distribution characteristics of resistance genes in 7918 CREC isolates belonging to 497 sequence types (ST) and originating from 75 countries. In the last decade, there has been a transition in the prevailing STs from highly virulent ST131 and ST38 to higher antibiotic-resistant ST410 and ST167. The rise of multi-drug resistant strains of CREC carrying plasmids with extended-spectrum beta-lactamase (ESBL) resistance genes could be attributed to three important instances of host-switching events. The spread of CREC was associated with the changing trends in <jats:italic>bla<\/jats:italic><jats:sub>NDM-5<\/jats:sub>, <jats:italic>bla<\/jats:italic><jats:sub>KPC-2<\/jats:sub>, and <jats:italic>bla<\/jats:italic><jats:sub>OXA-48<\/jats:sub>, as well as the plasmids IncFI, IncFII, and IncI. There were intercontinental geographic transfers of major CREC strains. Various crucial transmission hubs and patterns have been identified for ST131 in the United Kingdom, Italy, the United States, and China, ST167 in India, France, Egypt, and the United States, and ST410 in Thailand, Israel, the United Kingdom, France, and the United States. 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