The rise and global spread of IMP carbapenemases (1996–2023): a genomic epidemiology study
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background
IMP carbapenemases confer extensive drug resistance and are increasingly noted worldwide. Despite this, little is known regarding the global epidemiology of IMP carbapenemases.
Methods
We comprehensively identified bla IMP genes in all publicly available bacterial genomes, then systematically analysed the distribution of variants across species, lineages, plasmids and mobile elements, examining patterns over time, across geographic regions and by source. Structural analysis of IMP variants was performed.
Findings
4,556 bla IMP -containing genomes were identified from 1996-2023, including 52 bla IMP variants across 93 bacterial species. 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 were regionally endemic in Southeast Asia and North America, respectively. bla IMP dissemination was driven by horizontal gene transfer, facilitating inter-species spread. Proliferation of multidrug-resistant Enterobacter hormaechei , Pseudomonas aeruginosa and Klebsiella pneumoniae lineages led to local outbreaks. Dereplication removed 3,175/4,556 (69.9%) genomes, indicating that most bla IMP -containing genomes were highly related. bla IMP variants were associated with mobile genetic element combinations including class 1 integrons and insertion sequences (99.7%), aiding mobilisation into ≥52 plasmid clusters, predominantly IncHI2A, IncN, IncL/M and IncC. Genomes of environmental and animal origin accounted for 10.0% and 1.1% of the dataset, respectively. Evidence of cross-source transmission was limited, with most spillover occurring between genomes of human and environmental origin. Structural analysis revealed a conserved carbapenemase structure (mean lDDT 0.977), with convergent missense mutations at seven catalytically relevant sites.
Interpretation
Global analysis enabled us to historically reconstruct the emergence and variant-specific epidemiologies of bla IMP carbapenemase genes. Intersecting mobile elements enabled bla IMP genes to spread across multiple plasmids and bacterial genera, facilitating global and multi-source spread within a One Health framework. Additionally, convergent evolutionary patterns indicate that IMP variants may continue evolving, potentially evading novel beta-lactam antimicrobial agents.
Funding
NHMRC EL1 (APP1176324) to N.M.; NHMRC PF (APP1117940) to A.Y.P.; NIH/NIAID R01AI175414 to A.G-S.
Research in context panel
Evidence before this study
Despite being a major cause of carbapenem resistance in Gram negative infections, little is known about the global epidemiology of IMP carbapenemases. IMP carbapenemases are metallo-beta-lactamases that were first identified in 1991 and have evolved into 96 different IMP variants. On May 21 2025, we searched all published reports available in PubMed using the terms “’IMP’ and ‘carbapenemase’ genomics NOT (Review[Publication Type]) NOT (Case Reports[Publication Type]) NOT PCR” with no language restrictions and no publication date restrictions. We identified 223 articles, 62 and 121 of which reported single species or a single study centre/country, respectively. Only 6 articles employed genomics to examine multi-species and multi-geographical isolates, though this was in the context of carbapenem resistance more broadly rather than IMP carbapenemases specifically. The most relevant study included 38 globally distributed genomes across four species and tracked seven blaIMP variants across mobile genetic elements.
Added value of this study
To our knowledge, this global characterisation provides the most comprehensive account of bla IMP carbapenemase gene epidemiology. To analyse the global distribution and diversity of bla IMP genes, we compiled all available public genome data resulting in a dataset of 4,646 genomes. This has allowed us to identify local, regional and international spread of bla IMP variants and determine the contributions of clonal expansion, plasmid proliferation and co-localised mobile genetic elements. We demonstrated that key bla IMP variants display global (IMP-1, IMP-4, IMP-7, IMP-8 and IMP-13) and regional (IMP-26 within Southeast Asia and IMP-27 within North America) endemicity and that these patterns have been previously unacknowledged, reframing the previous understanding that IMP carbapenemases were largely confined to the Asia-Pacific region. Our observation of convergent evolutionary patterns raise concern that IMP variants may continue to evolve, potentially evading new β-lactam antimicrobials. This analysis has revealed the under-recognised contribution IMP carbapenemases make to global carbapenem resistance.
Implications of all the available evidence
These findings provide the first comprehensive atlas of bla IMP carbapenemase gene dissemination and underscore the silent global spread of IMP carbapenemases. We note the critical need for enhanced surveillance systems, particularly in low- and middle-income countries, that can detect complex plasmid-mediated and mobile genetic element-associated spread, as we noted with bla IMP carbapenemase genes. Moreover, our analyses show that systematic sampling across human, animal, and environmental reservoirs is crucial to address the One Health dimensions of emerging antimicrobial resistance threats. The study provides a framework for future interventions aimed at tracking and stopping the spread of IMP carbapenemases and calls for co-ordinated, real-time public health responses to this growing challenge.
