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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Public Health | doi: 10.3389/fpubh.2019.00229

An outbreak of carbapenem-resistant and hypervirulent Klebsiella pneumoniae in an intensive care unit of a major teaching hospital in Wenzhou, China

  • 1School of Laboratory Medicine and Life Science, Wenzhou Medical University, China
  • 2Department of Clinical Laboratory, First Affiliated Hospital of Wenzhou Medical University, China
  • 3Infection and Immunity Program, Biomedicine Discovery Institute and Department of Microbiology, Monash University, Australia
  • 4School of Medicine, Fourth Affiliated Hospital of Zhejiang University School of Medicine, China
  • 5Department of Microbiology and Immunology, The Peter Doherty Institute, The University of Melbourne, Australia

Carbapenem-resistant, hypervirulent Klebsiella pneumoniae (CR-hvKP) has recently emerged as a significant threat to public health. In this study, 29 Klebsiella pneumoniae isolates were isolated from eight patients admitted to the intensive care unit (ICU) of a comprehensive teaching hospital located in China from March 2017 to January 2018. Clinical information of patients was the basis for the further analyses of the isolates including antimicrobial susceptibility tests, identification of antibiotic resistance and virulence gene determinants, multilocus sequence typing (MLST), XbaI-macrorestriction by pulsed-field gel electrophoresis (PFGE). Selected isolates representing distinct resistance profiles and virulence phenotypes were screened for hypervirulence in a Galleria mellonella larvae infection model.
In the course of the outbreak, the overall mortality rate of patients was 100% (n=8) attributed to complications arising from CR-hvKP infections. All isolates except one (28/29, 96.6%) were resistant to multiple antimicrobial agents, and harbored diverse resistance determinants that included the globally prevalent carbapenemase blaKPC-2. Most isolates had hypervirulent genotypes being positive for nineteen virulence-associated genes, including iutA (25/29, 86.2%), rmpA (27/29, 93.1%), ybtA (27/29, 93.1%), entB (29/29, 100%), fimH (29/29, 100%) and mrkD (29/29, 100%). MLST revealed ST11 for the majority of isolates (26/29, 89,7%). Infection assays demonstrated high mortality in the Galleria mellonella model with the highest LD50 values for three isolates (less than 105 CFU/mL) demonstrating the degree of hypervirulence of these CR-hvKP isolates, and is discussed relative to previous outbreaks of CR-hvKP.

Keywords: Klebsiella pneumoniae, Hypervirulent, multidrug resistance, ST11, Epidemiology

Received: 28 Mar 2019; Accepted: 30 Jul 2019.

Edited by:

Kai Zhou, Zhejiang University, China

Reviewed by:

Pedro Xavier-Elsas, Federal University of Rio de Janeiro, Brazil
Yvonne Pfeifer, Robert Koch Institute, Germany
Richard V. Goering, School of Medicine, Creighton University, United States  

Copyright: © 2019 Zhao, Zhang, Torres, Liu, Rocker, Zhang, Wang, Chen, Wen Zi, Lin, Strugnell, Zhang, Lithgow, Zhou and Cao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Trevor Lithgow, Monash University, Infection and Immunity Program, Biomedicine Discovery Institute and Department of Microbiology, Melbourne, 3800, Australia,
Prof. Tieli Zhou, First Affiliated Hospital of Wenzhou Medical University, Department of Clinical Laboratory, Wenzhou, 325000, Zhejiang Province, China,
Prof. Jianming Cao, Wenzhou Medical University, School of Laboratory Medicine and Life Science, Wenzhou, 325035, Zhejiang Province, China,