Triple carbapenemase-producing Klebsiella pneumoniae ST6668 resistant to novel β-lactam/β-lactamase inhibitor combinations and cefiderocol, Northern Italy, 2025.

Klebsiella pneumoniae ST6668 has recently emerged in Northern Italy, but data on its resistance architecture remain limited. We identified a K. pneumoniae ST6668 (KNVO1) strain co-producing NDM-1, VIM-1 and OXA-48 carbapenemases, via multiple megaplasmids, from an elderly hospitalized patient who experienced clinical deterioration during a prolonged period of healthcare exposure. KNVO1 showed resistance to all tested β-lactams, including novel β-lactam/β-lactamase inhibitor combinations and cefiderocol, with susceptibility retained only to colistin. Whole-genome sequencing confirmed the ST6668. Plasmidome included two megaplasmids (pKPC-CAV1321 and IncFIB:IncHI) carrying blaVIM-1 and blaNDM-1, respectively, and an IncL plasmid harbouring blaOXA-48. SNPs-based phylogeny demonstrated genomic distance to other ST6668 strains circulating locally, suggesting an independent introduction event. Conclusion. The convergence of three major carbapenemase families within ST6668, highlights the capacity of this clone to accumulate complex resistance determinants via megaplasmids, posing a serious threat to infection control and antimicrobial stewardship in healthcare settings.