Genomic investigation of multispecies and multivariant blaNDM outbreak reveals key role of horizontal plasmid transmission

Infect Control Hosp Epidemiol. 2024 Jun;45(6):709-716. doi: 10.1017/ice.2024.8. Epub 2024 Feb 12.

Abstract

Objectives: New Delhi metallo-β-lactamases (NDMs) are major contributors to the spread of carbapenem resistance globally. In Australia, NDMs were previously associated with international travel, but from 2019 we noted increasing incidence of NDM-positive clinical isolates. We investigated the clinical and genomic epidemiology of NDM carriage at a tertiary-care Australian hospital from 2016 to 2021.

Methods: We identified 49 patients with 84 NDM-carrying isolates in an institutional database, and we collected clinical data from electronic medical record. Short- and long-read whole genome sequencing was performed on all isolates. Completed genome assemblies were used to assess the genetic setting of blaNDM genes and to compare NDM plasmids.

Results: Of 49 patients, 38 (78%) were identified in 2019-2021 and only 11 (29%) of 38 reported prior travel, compared with 9 (82%) of 11 in 2016-2018 (P = .037). In patients with NDM infection, the crude 7-day mortality rate was 0% and the 30-day mortality rate was 14% (2 of 14 patients). NDMs were noted in 41 bacterial strains (ie, species and sequence type combinations). Across 13 plasmid groups, 4 NDM variants were detected: blaNDM-1, blaNDM-4, blaNDM-5, and blaNDM-7. We noted a change from a diverse NDM plasmid repertoire in 2016-2018 to the emergence of conserved blaNDM-1 IncN and blaNDM-7 IncX3 epidemic plasmids, with interstrain spread in 2019-2021. These plasmids were noted in 19 (50%) of 38 patients and 35 (51%) of 68 genomes in 2019-2021.

Conclusions: Increased NDM case numbers were due to local circulation of 2 epidemic plasmids with extensive interstrain transfer. Our findings underscore the challenges of outbreak detection when horizontal transmission of plasmids is the primary mode of spread.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Australia / epidemiology
  • Disease Outbreaks*
  • Enterobacteriaceae Infections / epidemiology
  • Enterobacteriaceae Infections / microbiology
  • Enterobacteriaceae Infections / transmission
  • Female
  • Gene Transfer, Horizontal
  • Genome, Bacterial
  • Humans
  • Male
  • Middle Aged
  • Plasmids* / genetics
  • Whole Genome Sequencing
  • beta-Lactamases* / genetics

Substances

  • beta-lactamase NDM-1