Within-host evolution drives the emergence of ceftazidime-avibactam resistance mediated by IncN plasmid-encoded <i>bla</i> <sub>NDM-1</sub> and <i>bla</i> <sub>KPC-33</sub> in ST11-KL64 hypervirulent <i>Klebsiella pneumoniae</i>
The alarming rise of ceftazidime-avibactam (CZA) resistance, primarily through <i>bla</i><sub>KPC</sub> mutations, constitutes a critical threat to global health. Here, we reported the within-host evolution of CZA resistance, driven by IncN plasmid-encoded <i>bla</i><sub>NDM-1</sub> and <i>bla</i><sub>KPC</sub> mutations, in a high-risk ST11-KL64 hypervirulent carbapenem-resistant <i>Klebsiella pneumoniae</i> lineage during patient therapy. Our study demonstrates the emergence of simultaneous, independent evolutionary pathways under CZA pressure. Crucially, an IncN <i>bla</i><sub>NDM-1</sub> plasmid acted as a helper plasmid, facilitating co-transfer of <i>bla</i><sub>NDM-1</sub> with <i>bla</i><sub>KPC-2</sub> and virulence genes. These direct insights highlight the urgent need for enhanced genomic surveillance against this evolving threat.
Authors
- Qi Han (ORCID: https://orcid.org/0000-0002-3264-9571)
- Young-Ho Song (ORCID: https://orcid.org/0000-0002-3430-1544)
- Peiwen Xia
- Shiyu Tang (ORCID: https://orcid.org/0000-0001-6503-5878)
- Yong Li (ORCID: https://orcid.org/0000-0003-4038-0493)
- Na Huang (ORCID: https://orcid.org/0000-0002-8298-786X)
- Y Xia
- Y. Liu
- Tingting Si
Institutions
- The Affiliated Yongchuan Hospital of Chongqing Medical University (CN)
- Chongqing Medical University (CN)
Publication Details
- Journal
- Microbiology Spectrum
- Published
- 2026-02-19
- DOI
- https://doi.org/10.1128/spectrum.02367-25
- Primary Topic
- Antibiotic Resistance in Bacteria
- Type
- article
- Field-Weighted Citation Impact
- 0.00