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. 2025 Jul 2;25(1):376.
doi: 10.1186/s12866-025-04096-z.

Nosocomial transmission, adaption and clinical outcomes of carbapenem-resistant hypervirulent Klebsiella pneumoniae

Yanjun Liu  1 , Zhiqian Wang  1 , Zijuan Jian  1 , Peilin Liu  1 , Yanming Li  1 , Fang Qin  1 , Qun Yan  1 , Wenen Liu  2   3
Affiliations

Nosocomial transmission, adaption and clinical outcomes of carbapenem-resistant hypervirulent Klebsiella pneumoniae

Yanjun Liu et al. BMC Microbiol. .

Abstract

Background: Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-HvKp) poses a significant threat in healthcare settings. This study investigates the nosocomial transmission dynamics, adaptive phenotypes, and clinical outcomes of CR-HvKp with different evolutionary patterns.

Methods: A genomic analysis of 2,002 Klebsiella pneumoniae isolates collected from a major teaching hospital in China was performed to identify convergent isolates. Epidemiological features, including CR-HvKp nosocomial transmission, were assessed. Selected isolates underwent phenotypic testing to evaluate adaptive traits. Clinical outcomes were analyzed retrospectively using electronic medical records.

Results: A total of 127 CR-HvKp were characterized, with ST11-KL64 hv-CRKP (carbapenem resistant Klebsiella pneumoniae acquired hypervirulence) as the predominant sequence type. CR-HvKp exhibited diverse evolutionary patterns linked to nosocomial transmission, particularly in the ICU. ST11-KL64 hv-CRKP demonstrated robust transmission within ICU settings. Compared to CRKP, hv-CRKP showed enhanced in vitro competitiveness and superior immune evasion. CR-HvKp infections were significantly associated with higher mortality rates, especially involved in sepsis or septic shock (P < 0.0001).

Conclusion: The ST11-KL64 hv-CRKP clonal complex is highly prevalent in CR-HvKp and demonstrates significant nosocomial transmission, particularly within ICU settings. Timely and effective sepsis management is critical to improving survival outcomes in CR-HvKp infections. Continuous genomic surveillance is imperative to control the spread of these pathogens.

Keywords: Adaptation; Carbapenem-resistant hypervirulent Klebsiella pneumoniae; Clinical outcomes; Evolutionary patterns; Nosocomial transmission.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of Xiangya Hospital of Central South University (ID 202212295, Changsha, Hunan Province, China). Because this was a retrospective study involving the collection of KP strains and anonymized clinical data from patients, the Ethics Committee of Xiangya Hospital of Central South University passed the exemption condition for informed consent. Meanwhile, the animal experiments in the study were approved by the Experimental Animal Ethics Committee of Xiangya Hospital of Central South University under the approval number 202409155. Specifically, following bacterial inoculation and before surgery, mice are anaesthetised with 0.1% pentobarbital at a dose of 0.15 mg per 20 g of body weight. At this point, they are unconscious and insensate to pain. Subsequently, they are euthanised by rapid cervical dislocation. This method was selected as it adheres to ethical guidelines for animal welfare, ensuring a humane and rapid euthanasia process with minimal distress to the animals. It is also a widely accepted technique in research settings.We declare that our research strictly adheres to the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Heat map of carbapenem-resistant hypervirulent K. pneumoniae (CR-HvKp) virulence, resistance, and plasmid replicon distribution. The green color in the heatmap represents the presence of a gene or plasmid replicon, and the absence of color represents the absence of a gene or plasmid replicon. The different colors in the top row represent different evolutionary patterns
Fig. 2
Fig. 2
Phylogenetic tree of 127 CR-HvKp strains and their nosocomial transmission trajectories. a Phylogenetic analysis of 127 K. pneumoniae strains. Maximum likelihood phylogenetic tree constructed by core genome single-nucleotide polymorphisms (cgSNPs). Circles outside the tree (from inside to outside) indicate the sequence type(ST), K locus(KL), source specimen, collection date and source department/ward. Green, blue, red, and purple on the evolutionary tree branches represent ST11-KL64, ST11-KL-47, ST420-KL20, and ST25-KL2 CR-HvKp respectively, for which clonal transmission occurred. Strain numbers with an SNP difference of 0 are labeled in red. Event 1 with nosocomial clonal spread of ST11-KL64 hv-CRKP is shaded in lavender; event 2 is labeled in pink. b Nosocomial transmission of nine strains of ST11-64 occurred between April 2016 and November 2016 (event 1). c Nosocomial transmission of eight strains of ST11-64 occurred between June 2017 and November 2017(event 2)
Fig. 3
Fig. 3
Virulence phenotypes of CR-HvKp and its control bacteria. a transmission electron microscopy images of representative Kp; b centrifugation for mucus content; c siderophore detection. Statistical analysis were performed using one-way ANOVA. dGalleria mellonella infection model of CR-HvKP strains vs. control strains. Statistical analysis was performed using Kaplan–Meier analysis and log-rank test.e Biofilm forming ability of CR-HvKp vs. control strains. Statistical analysis was performed using one-way ANOVA. *p < 0.05, **p < 0.01, ***p < 0.001, ****P < 0.0001. Results were plotted using GraphPad Prism v.7.00 (GraphPad Software Inc., La Jolla, CA, USA)
Fig. 4
Fig. 4
Adaptive results of survival in vitro between CR-HvKp and control bacteria. a Growth curves (24-h) of CR-HvKp and control strains (CR-hvKP vs. HvKp, hv-CRKP vs. CRKP), statistical analyses were performed using multiple t-tests. b In vitro competition assay of CR-HvKp strains and control strains. Statistical analysis was performed using one-way ANOVA. *p < 0.05, **p < 0.01, ***p < 0.001, ****P < 0.0001. Results were plotted using GraphPad Prism v.7.00 (GraphPad Software Inc., La Jolla, CA, USA)
Fig. 5
Fig. 5
Adaptive results of host interactions between CR-HvKp and control bacteria. a Lung epithelial cell adhesion test of CR-HvKp vs. control strains. b Macrophage phagocytosis assay of CR-HvKp vs. control strains.c Neutrophil phagocytosis assay of CR-HvKp vs. control strains. Statistical analysis were performed using one-way ANOVA. *p < 0.05, **p < 0.01, ***p < 0.001, ****P < 0.0001. Results were plotted using GraphPad Prism v.7.00 (GraphPad Software Inc., La Jolla, CA, USA). d The survival curve of mice infected with 107 CFU CR-HvKp strains and control strains. Statistical analysis was performed using Kaplan–Meier analysis and log-rank test. e Bacteria burden of various organs from mice infected by 107 CFU CR-HvKp and control bacteria
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