Multi-species plasmids and K. pneumoniae clonal spread contribute to bla NDM outbreak across seven UK healthcare sites
Caitlin Duggan, Charlotte Brookfield, David Lawrie, Victoria Owen, Timothy Neal, James Cruise, Alice J Fraser, Lewis Kelly, Fabrice E Graf, Daire Cantillon, Joseph M Lewis, Thomas Edwards, Eva HeinzAbstract
Objectives
The NDM carbapenemase enables Gram-negative bacteria to hydrolyse almost all β-lactam antibiotics. In 2023, a large increase of blaNDM in clinical isolates was identified in a clinical microbiology laboratory serving hospitals and GP practices in Merseyside, UK, raising concerns of a larger outbreak.
Methods
We used short-read WGS and bioinformatic analyses to identify the outbreak(s) and identify potential links by combining with anonymized, routinely collected clinical metadata. A subset of isolates were long-read sequenced to analyse resistance genes and plasmids at maximum resolution.
Results
The outbreak included Enterobacter hormaechei, Klebsiella pneumoniae, Escherichia coli, Citrobacter freundii, Citrobacter braakii and Enterobacter kobei and 28 STs. K. pneumoniae ST101 represented the only major clonal expansion (18/21 K. pneumoniae isolates), and combination with metadata strongly suggested a multi-site hospital-associated outbreak. We identified four variants of blaNDM, and long-read sequencing indicated blaNDM-1 spread across species was driven by an IncHI2/IncHI2A plasmid, representing 82% of blaNDM1 isolates.
Conclusions
This study captured an outbreak of blaNDM-positive Enterobacterales across eight healthcare settings and highlights the complex epidemiology of spread mediated by both expansion of successful lineages (K. pneumoniae ST101) and multi-species plasmids (IncHI2/IncHI2A). It also highlights the challenge of recognizing and tracing an outbreak linked to patients moving across different healthcare systems and the importance of linked surveillance systems.