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Published on: March 16, 2012
Outbreak of IncX8 Plasmid-Mediated KPC-3-Producing Enterobacterales Infection, China
Abstract:
Carbapenem-resistant Enterobacterales (CRE) infection is highly endemic in China; Klebsiella pneumoniae carbapenemase (KPC) 2-producing CRE is the most common, whereas KPC-3-producing CRE is rare. We report an outbreak of KPC-3-producing Enterobacterales infection in China. During August 2020-June 2021, 25 blaKPC-3-positive Enterobacteriale isolates were detected from 24 patients in China. Whole-genome sequencing analysis revealed that the blaKPC-3 genes were harbored by IncX8 plasmids. The outbreak involved clonal expansion of KPC-3-producing Serratia marcescens and transmission of blaKPC-3 plasmids across different species. The blaKPC-3 plasmids demonstrated high conjugation frequencies (10-3 to 10-4). A Galleria mellonella infection model showed that 2 sequence type 65 K2 K. pneumoniae strains containing blaKPC-3 plasmids were highly virulent. A ceftazidime/avibactam in vitro selection assay indicated that the KPC-3-producing strains can readily develop resistance. The spread of blaKPC-3-harboring IncX8 plasmids and these KPC-3 strains should be closely monitored in China and globally.
Insights
An outbreak of rare KPC-3 carbapenem-resistant Enterobacterales (CRE) occurred in China, driven by IncX8 plasmids. These strains showed high virulence and rapid resistance development, necessitating global monitoring.
Area of Science:
- Microbiology
- Infectious Diseases
- Genomics
Background:
- Carbapenem-resistant Enterobacterales (CRE) are a significant global health threat.
- Klebsiella pneumoniae carbapenemase (KPC)-2-producing CRE is common in China, but KPC-3 is rare.
- An unusual outbreak of KPC-3-producing CRE was identified in China.
Purpose of the Study:
- To investigate an outbreak of KPC-3-producing Enterobacterales in China.
- To characterize the genetic elements and transmission dynamics of blaKPC-3.
- To assess the virulence and resistance potential of these emerging strains.
Main Methods:
- Detection and WGS analysis of 25 blaKPC-3-positive Enterobacteriale isolates.
- Plasmid analysis, conjugation experiments, and virulence assessment using a Galleria mellonella model.
- In vitro selection assay for ceftazidime/avibactam resistance.
Main Results:
- The outbreak involved 24 patients and 25 isolates between August 2020 and June 2021.
- blaKPC-3 genes were located on IncX8 plasmids, facilitating interspecies transmission.
- KPC-3-producing Serratia marcescens clonal expansion and plasmid transmission occurred.
- K. pneumoniae strains with blaKPC-3 plasmids exhibited high virulence.
- KPC-3 strains rapidly developed resistance to ceftazidime/avibactam in vitro.
Conclusions:
- This study reports a rare outbreak of KPC-3-producing CRE in China.
- IncX8 plasmids play a crucial role in the spread of blaKPC-3 across different Enterobacterales species.
- The high virulence and rapid resistance development underscore the need for close monitoring of these strains and plasmids globally.
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