The rise and global spread of IMP carbapenemases (1996-2023): a genomic epidemiology study

Infections caused by carbapenemase-producing organisms are a global health threat. IMP carbapenemases are one of the key drivers of these infections but little is known regarding their global epidemiology. We analyse three decades of bla_IMP gene spread using sequence data from 4556 genomes collected between 1996-2023. A total of 52 bla_IMP variants were identified across 93 bacterial species. We reconstruct the historical emergence and variant-specific epidemiologies of bla_IMP genes and showed how key variants (bla_IMP-1, bla_IMP-4, bla_IMP-7, bla_IMP-8 and bla_IMP-13) achieved global endemicity, while bla_IMP-26 and bla_IMP-27 became regionally endemic in Southeast Asia and North America, respectively. Dissemination was driven predominantly by horizontal gene transfer facilitated by mobile genetic elements such as class 1 integrons and insertion sequences. These elements mobilised bla_IMP genes into 52 distinct plasmid clusters (predominantly IncHI2A, IncN, IncL/M, and IncC), enabling broad inter-species transmission. Despite limited overall cross-source transmission, spillover primarily occurred between human and environmental reservoirs. Structural analysis revealed conserved IMP carbapenemase structure (mean lDDT 0.977) with convergent missense mutations at seven catalytically relevant sites. Our analysis provides a framework for understanding bla_IMP dissemination, highlighting their emergence as an important, yet under-recognised, public health threat.