Global genomic epidemiology of multi-carbapenemase Enterobacterales

Abstract

Enterobacterales pathogens that encode multiple carbapenemase genes are an emerging public health threat. The genomic and plasmid context of the multi-carbapenemase producers has not yet been explored at scale. We analysed 1501 publicly-available global genomes that encoded two or more genes from the five prevalent carbapenemase families (IMP, KPC, NDM, OXA-48-like, and VIM). We observed 241 distinct allelic combinations, with NDM/OXA-48-like (25.6%), multiple KPC (25.3%), KPC/NDM (18.8%), and multiple NDM (10.9%) being the most common groups. We found that many genomes were part of high-risk lineages (48.0%). Most genomes carried carbapenemase genes on two plasmids (59.2%) or one plasmid (23.5%), and most genomes encoded different carbapenemase families (56.2%) rather than copies of the same allele (36.2%). We observed multiple mechanisms of multi-carbapenemase evolution including plasmid co-integration, convergence with virulence, and generation of novel allele diversity through duplication. Multi-carbapenemase plasmids had more AMR genes that conferred resistance to more AMR classes compared to plasmids encoding a single carbapenemase. The proportion of cross-class combinations (KPC/NDM and NDM/OXA-48-like) increased significantly over time, with NDM-5/OXA-181 (3.3-fold) and NDM-4/OXA-181 (8.9-fold) combinations enriched. These findings provide valuable insights into the genomic features of multi-carbapenemase Enterobacterales to support the development of effective surveillance programmes.

Genomic epidemiology of dual carbapenemase-producing Klebsiella pneumoniae and identification of an ST23-KL1 blaKPC-2/blaIMP-4 co-producing isolate in a Chinese tertiary hospital
Haijun Li, Saiqi Qi, Jilei Ma +6
Frontiers in Microbiology2 Nov 2026Peer-reviewedCC BY 4.0MicrobiologyFrontiersCrossref
Antimicrobial resistance at the animal / environment interface: phenotypic detection and persistence of ESBL and carbapenemase producing Enterobacterales in Irish cattle systems
M. C. Quinn, C. J. O'Shea, L. Geraghty
bioRxiv22 Sep 2026PreprintAll rights reservedFull textMicrobiologybioRxiv
Inoculum-dependent activity of contemporary β-lactam agents against carbapenemase- producing Enterobacterales
Tokeshwar Kumar Sahu, Pravin Gadkari, Jaishriram Rathored
Frontiers in Microbiology12 Oct 2026Peer-reviewedCC BY 4.0Full textMicrobiologyPMCCrossrefEurope PMC
Carbapenemase-producing rare Enterobacterales in hospital food: a Latin American one health blind spot
Bianca L C de Godoy, Giovana Rosa, Mara C L Nogueira +2
Frontiers in Microbiology7 Oct 2026Peer-reviewedCC BY 4.0Full textMicrobiologyCrossrefEurope PMC
Divergent epidemic trajectories of ESBL-producing and carbapenemase-producing Enterobacterales in French hospitals: a nationwide modelling study
Benjamin Davido, Louise Rouillard, Pierre Leroux +2
Journal of Hospital Infection21 Oct 2026Peer-reviewedCC BYFull textGeneral biologyHAL

Cite

BibTeX RIS

BibTeX

@misc{lerminiaux2026global,
  title = {{Global genomic epidemiology of multi-carbapenemase Enterobacterales}},
  author = {N. Lerminiaux and D. Nagy and S. Lipworth and The NEKSUS Consortium and L. P. Shaw and L. Mataseje and K. L. Hopkins and K. Chau and N. Stoesser},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.07.757280},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.07.757280v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - Global genomic epidemiology of multi-carbapenemase Enterobacterales
AU  - N. Lerminiaux
AU  - D. Nagy
AU  - S. Lipworth
AU  - The NEKSUS Consortium
AU  - L. P. Shaw
AU  - L. Mataseje
AU  - K. L. Hopkins
AU  - K. Chau
AU  - N. Stoesser
PY  - 2026
DA  - 2026/10/07
PB  - bioRxiv
DO  - 10.64898/2026.10.07.757280
UR  - https://www.biorxiv.org/content/10.64898/2026.10.07.757280v1
AB  - Enterobacterales pathogens that encode multiple carbapenemase genes are an emerging public health threat. The genomic and plasmid context of the multi-carbapenemase producers has not yet been explored at scale. We analysed 1501 publicly-available global genomes that encoded two or more genes from the five prevalent carbapenemase families (IMP, KPC, NDM, OXA-48-like, and VIM). We observed 241 distinct allelic combinations, with NDM/OXA-48-like (25.6%), multiple KPC (25.3%), KPC/NDM (18.8%), and multiple NDM (10.9%) being the most common groups. We found that many genomes were part of high-risk lineages (48.0%). Most genomes carried carbapenemase genes on two plasmids (59.2%) or one plasmid (23.5%), and most genomes encoded different carbapenemase families (56.2%) rather than copies of the same allele (36.2%). We observed multiple mechanisms of multi-carbapenemase evolution including plasmid co-integration, convergence with virulence, and generation of novel allele diversity through duplication. Multi-carbapenemase plasmids had more AMR genes that conferred resistance to more AMR classes compared to plasmids encoding a single carbapenemase. The proportion of cross-class combinations (KPC/NDM and NDM/OXA-48-like) increased significantly over time, with NDM-5/OXA-181 (3.3-fold) and NDM-4/OXA-181 (8.9-fold) combinations enriched. These findings provide valuable insights into the genomic features of multi-carbapenemase Enterobacterales to support the development of effective surveillance programmes.
ER  -

Abstract

Related

Cite