Multi-speciesblaNDMoutbreak in multiple tertiary and a primary healthcare facility in Merseyside, UK, driven by a combination of multi-species plasmids and small clonal outbreaks
Abstract
Background
TheblaNDMcarbapenemase gene provides Gram-negative bacteria the ability to hydrolyse almost all β-lactam antibiotics. A 90% year on year increase from 2022 to 2023 in prevalence ofblaNDMin clinical isolates was identified in a clinical microbiology laboratory serving Merseyside, UK hospitals and GP practices in 2023. We analysed isolates identified to disclose the species and plasmid diversity and to understand the mechanism of dissemination ofblaNDMacross Merseyside hospitals.
Methods
Data regarding the sample type, the isolation date and location of samples was collected and analysed to establish initial transmission hypotheses; 64 Gram-negative bacterial isolates which tested positive forblaNDMusing routine diagnostics underwent short read whole-genome sequencing. The samples were derived from seven Merseyside hospitals and a Merseyside GP practice, of these, 24 were also long-read sequenced to produce local reference assemblies and enable us to confidently resolve resistance gene locations and plasmids.
Results
Overall, six species were identified, includingEnterobacter hormaechei(n=22)Klebsiella pneumoniae(n=21),Escherichia coli(n=15)Citrobacter freundii(n=3),Citrobacter brakii(n=1) andEnterobacter kobei(n=1). Most multi-isolate species belonged to a number of sequence types (IQR, 1-10), apart fromK. pneumoniaewhere 18/21 were ST101. Four variants ofblaNDMwere identified:blaNDM-1(n=43),blaNDM-5(n=12),blaNDM-6(n=1),blaNDM-14(n=1), and in six isolatesblaNDMwas not identified by sequencing. Long-read sequencing of 24 representative isolates found thatblaNDM-1was commonly encoded by a IncHI2/IncHI2A plasmid (82.4%, n=14) whereasblaNDM-5, (n=4) was encoded on different plasmids in each isolate but had the same conserved gene cassette includingblaNDM-5in all instances. Potential evidence of transposition events was noted in two isolates, whereblaNDM-1was found on a small (8.5kbp) untypable plasmid.
Conclusions
This study captures an outbreak ofblaNDMpositiveEnterobacteralesin Merseyside hospitals and highlights the complex epidemiology of spread mediated both by expansion of successful lineages (K. pneumoniaeST101) and plasmids. A dominant IncHI2/IncHI2A plasmid that has disseminatedblaNDM-1across different species and subsequently led to small clonal outbreaks within-hospitals. This highlights the cross-species movement of AMR elements as an important factor in AMR dissemination, and the importance of both species-specific surveillance to monitor local outbreaks, but also species-agnostic surveillance to include plasmids spreading across species.
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