Abstract
Carbapenem-resistant, hypervirulent Klebsiella pneumoniae (CR-hvKP) has recently emerged as a significant threat to public health. In this study, 29 K. 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 19 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 (<105 CFU/mL) demonstrating the degree of hypervirulence of these CR-hvKP isolates, and is discussed relative to previous outbreaks of CR-hvKP.
Highlights
Klebsiella pneumoniae is a Gram-negative pathogen causing hospital-acquired infections, especially for immunocompromised patients in the intensive care units (ICU) [1,2,3]
Our study reported an outbreak of ST11 K. pneumoniae in the ICU of a teaching hospital where multiple isolates showed highly multiple-drug resistance phenotypes including carbapenem-resistance
Isolates were taken under a surveillance protocol aimed at patient care, which means sampling bias interferes with drawing strong conclusions on the extent of in host evolution vs. transmission and re-infection by multiple ST11 K. pneumoniae strains
Summary
Klebsiella pneumoniae is a Gram-negative pathogen causing hospital-acquired infections, especially for immunocompromised patients in the intensive care units (ICU) [1,2,3]. There is mounting evidence that hvKp secrete factors which impact the epithelia and microbiome, such as the cell-cycle modulating non-ribosomal peptide colibactin and the channel-forming bacteriocin microcin E492 [6, 7], respectively These factors modify the host niche and might thereby contribute to the observed increase in virulence [6, 8]. The significance of these features has been established in the measurement of virulence phenotype in vitro and in vivo [9,10,11], and whole genome sequence analyses document the range of genes for iron-acquisition, enhanced capsule secretion, and toxin secretion. These include iron-binding siderophores: aerobactin, yersiniabactin, and salmochelin, as well as TonBdependent transporters for iron (Kfu), iron dicitrate (Fec), and ferric siderophores (FyuA) [7, 12]
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