Genome Medicine (Apr 2024)

The emergence of highly resistant and hypervirulent Klebsiella pneumoniae CC14 clone in a tertiary hospital over 8 years

  • Sharif Hala,
  • Mohammed Malaikah,
  • Jiayi Huang,
  • Wesam Bahitham,
  • Omniya Fallatah,
  • Samer Zakri,
  • Chakkiath Paul Antony,
  • Mohammed Alshehri,
  • Raeece Naeem Ghazzali,
  • Fathia Ben-Rached,
  • Abdullah Alsahafi,
  • Asim Alsaedi,
  • Ghadeer AlAhmadi,
  • Mai Kaaki,
  • Meshari Alazmi,
  • Baraa AlhajHussein,
  • Muhammad Yaseen,
  • Hosam M. Zowawi,
  • Majed F. Alghoribi,
  • Abdulhakeem O. Althaqafi,
  • Abdulfattah Al-Amri,
  • Danesh Moradigaravand,
  • Arnab Pain

DOI
https://doi.org/10.1186/s13073-024-01332-5
Journal volume & issue
Vol. 16, no. 1
pp. 1 – 19

Abstract

Read online

Abstract Background Klebsiella pneumoniae is a major bacterial and opportunistic human pathogen, increasingly recognized as a healthcare burden globally. The convergence of resistance and virulence in K. pneumoniae strains has led to the formation of hypervirulent and multidrug-resistant strains with dual risk, limiting treatment options. K. pneumoniae clones are known to emerge locally and spread globally. Therefore, an understanding of the dynamics and evolution of the emerging strains in hospitals is warranted to prevent future outbreaks. Methods In this study, we conducted an in-depth genomic analysis on a large-scale collection of 328 multidrug-resistant (MDR) K. pneumoniae strains recovered from 239 patients from a single major hospital in the western coastal city of Jeddah in Saudi Arabia from 2014 through 2022. We employed a broad range of phylogenetic and phylodynamic methods to understand the evolution of the predominant clones on epidemiological time scales, virulence and resistance determinants, and their dynamics. We also integrated the genomic data with detailed electronic health record (EHR) data for the patients to understand the clinical implications of the resistance and virulence of different strains. Results We discovered a diverse population underlying the infections, with most strains belonging to Clonal Complex 14 (CC14) exhibiting dominance. Specifically, we observed the emergence and continuous expansion of strains belonging to the dominant ST2096 in the CC14 clade across hospital wards in recent years. These strains acquired resistance mutations against colistin and extended spectrum β-lactamase (ESBL) and carbapenemase genes, namely bla OXA-48 and bla OXA-232, located on three distinct plasmids, on epidemiological time scales. Strains of ST2096 exhibited a high virulence level with the presence of the siderophore aerobactin (iuc) locus situated on the same mosaic plasmid as the ESBL gene. Integration of ST2096 with EHR data confirmed the significant link between colonization by ST2096 and the diagnosis of sepsis and elevated in-hospital mortality (p-value < 0.05). Conclusions Overall, these results demonstrate the clinical significance of ST2096 clones and illustrate the rapid evolution of an emerging hypervirulent and MDR K. pneumoniae in a clinical setting.

Keywords