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An Outbreak of Carbapenem-Resistant and Hypervirulent Klebsiella pneumoniae in an Intensive Care Unit of a Major Teaching Hospital in Wenzhou, China

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TLDR
Infection assays demonstrated high mortality in the Galleria mellonella model with the highest LD50 values for three isolates (<105 CFU/mL) demonstrating the degree of hypervirulence of these CR-hvKP isolates, and is discussed relative to previous outbreaks.
Abstract
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.

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Journal ArticleDOI

Carbapenem Resistance-Encoding and Virulence-Encoding Conjugative Plasmids in Klebsiella pneumoniae.

TL;DR: Identifying the key molecular markers of resistance and virulence-bearing conjugative plasmids allows improved tracking and control of the life-threatening carbapenem-resistant and hypervirulent strains of K. pneumoniae.
Journal ArticleDOI

Virulence evolution, molecular mechanisms of resistance and prevalence of ST11 carbapenem-resistant Klebsiella pneumoniae in China: A review over the last 10 years.

TL;DR: This review traces the prevalence of ST11 CRKP in China Antimicrobial Surveillance Network (CHINET), the key drug resistance mechanisms, and virulence evolution, and demonstrates a very close linkage among IncF plasmids, NTEKPC, and ST11 Klebsiella pneumoniae in China.
Journal ArticleDOI

A global perspective on the convergence of hypervirulence and carbapenem resistance in Klebsiella pneumoniae.

TL;DR: In this paper, the emergence of carbapenem-resistant Klebsiella pneumoniae (CR-hvKP) was investigated and three patterns were identified: acquiring a hypervirulent phenotype, acquiring a carbapenzem-resistance phenotype, and acquiring both hypervirulence hybrid plasmid.
Journal ArticleDOI

The Small Protein RmpD Drives Hypermucoviscosity in Klebsiella pneumoniae.

TL;DR: A model in which the RMPA-associated phenotypes are largely due to RmpA activating the expression of rmpD to produce HMV and rmpC to stimulate cps expression is suggested, suggesting that capsule production and HMV may be separable traits.
Posted ContentDOI

The small protein RmpD drives hypermucoviscosity in Klebsiella pneumoniae

TL;DR: A new gene (rmpD) required for HMV but does not contribute to capsule production is identified, which suggests a model in which the RmpA-associated phenotypes are largely due to RMPA activating the expression of rmpD to produce HMV and rmpC to stimulate cps expression.
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Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria

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Hypervirulent (hypermucoviscous) Klebsiella pneumoniae: A new and dangerous breed

TL;DR: A new hypervirulent (hypermucoviscous) variant of Klebsiella pneumoniae has emerged and the majority of cases described to date are in Asians, raising the issue of a genetic predisposition vs. geospecific strain acquisition.
Journal ArticleDOI

A Novel Virulence Gene in Klebsiella pneumoniae Strains Causing Primary Liver Abscess and Septic Metastatic Complications

TL;DR: It is concluded that magA fits molecular Koch's postulates as a virulence gene and can be used as a marker for the rapid diagnosis and for tracing the source of this emerging infectious disease.
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