Drug Resistance and Molecular Characteristics of Carbapenem-Resistant OXA-48-Producing Klebsiella pneumoniae Strains in Hainan, China

Microorganisms. 2023 Dec 27;12(1):49. doi: 10.3390/microorganisms12010049.

Abstract

Background: The emergence and global spread of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) are of great concern to health services worldwide. These β-lactamases hydrolyze almost all β-lactams, are plasmid-encoded, and are easily transferable among bacterial species. They are mostly of the KPC types in CR-hvKp. OXA-48-producing hvKP strains have been rarely reported in the literature.

Methods: OXA-48-producing hvKP strains were collected from clinical specimens at the First Affiliated Hospital of Hainan Medical University from January 2022 to March 2023. Hypervirulent strains were tested for virulence in a mouse lethality study and underwent whole genome sequencing to identify genomic features.

Results: A total of 42 unique OXA-48-bearing K. pneumoniae strains were identified, including three CR-hvKP strains (KP2683-1, NCRE61, and KP2185), which were isolated from bacteremia, pulmonary abscess, and liver abscess separately. The three CR-hvKP strains belonged to two different clones of ST11 KL64 (KP2185 and NCRE61) and ST23 K1 (KP2683-1). The KP2683-1 strain had the highest virulence. Whole genome sequencing analysis indicated that NCRE61 and KP2185 acquired IncFIB-type plasmids with a set of virulence genes (iroBCDN, iucABCD, iutA, rmpA, and rmpA2), while KP2683-1 acquired an IncL-type blaOXA-48-harboring plasmid. Consecutive cultures showed that the blaOXA-48-harboring plasmids were highly stable in the three hvKP strains and could be transmitted to Escherichia coli J53 by conjugation. The drug susceptibility testing results show that Ceftazidime/avibactam is sensitive for OXA-48-producing hvKP.

Conclusions: Our study highlighted the two evolutionary pathways of OXA-48-producing hvKP strains and confirmed their virulence through in vivo testing. Ceftazidime/avibactam may be a viable option for treating OXA-48-producing hvKP strains.

Keywords: Klebsiella pneumoniae; OXA-48; carbapenemase; hypervirulent strain.

Publication types

  • Retracted Publication

Grants and funding

The present study was supported by the National Natural Science Foundation of China (grant nos. 82360003). The project is supported by the Education Department of Hainan Province, project number: Hnky2022ZD-11. The present study was also supported by the Hainan Provincial Natural Science Foundation of China, project number: 822MS176. The present study was supported by the Hainan Provincial Natural Science Foundation of China (grant nos. GHYF2022011, ZDKJ2021036, ZDYF2020223 and 820CXTD448) and the National Natural Science Foundation of China (grant nos. 82160012, 82260001, 82311530776). The project is supported by the Hainan Province Clinical Medical Center.