Multi-species bla NDM outbreak in multiple tertiary and a primary healthcare facility in Merseyside, UK, driven by a combination of multi-species plasmids and small clonal outbreaks
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Background
The bla NDM carbapenemase 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 of bla NDM in 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 of bla NDM across 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 for bla NDM using 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, including Enterobacter hormaechei (n=22) Klebsiella pneumoniae (n=21), Escherichia coli (n=15) Citrobacter freundii (n=3), Citrobacter brakii (n=1) and Enterobacter kobei (n=1). Most multi-isolate species belonged to a number of sequence types (IQR, 1-10), apart from K. pneumoniae where 18/21 were ST101. Four variants of bla NDM were identified: bla NDM-1 (n=43), bla NDM-5 (n=12), bla NDM-6 (n=1), bla NDM-14 (n=1), and in six isolates bla NDM was not identified by sequencing. Long-read sequencing of 24 representative isolates found that bla NDM-1 was commonly encoded by a IncHI2/IncHI2A plasmid (82.4%, n=14) whereas bla NDM-5 , (n=4) was encoded on different plasmids in each isolate but had the same conserved gene cassette including bla NDM-5 in all instances. Potential evidence of transposition events was noted in two isolates, where bla NDM-1 was found on a small (8.5kbp) untypable plasmid.
Conclusions
This study captures an outbreak of bla NDM positive Enterobacterales in Merseyside hospitals and highlights the complex epidemiology of spread mediated both by expansion of successful lineages ( K. pneumoniae ST101) and plasmids. A dominant IncHI2/IncHI2A plasmid that has disseminated bla NDM-1 across 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.
