Genomic analyses identify nosocomial transmission of ST23 carbapenem-resistant hypervirulent Klebsiella pneumoniae mediated by a conjugative IncFIIK2 NDM-1 plasmid.
This study highlights the need for enhanced surveillance of plasmid transmission in Klebsiella pneumoniae to mitigate public health risks.
Where it sits
this study against the rest of the tirzepatide corpusSummary and findings
This study identified and characterized ST23 carbapenem-resistant hypervirulent Klebsiella pneumoniae bloodstream isolates from 2019-2023. Among 1069 CRKP bloodstream isolates, four ST23-K1 strains (0.37%) were detected, with clinical outcomes showing that three patients recovered after antibiotic therapy. The study emphasizes the importance of plasmid-focused surveillance due to the identified resistance mechanisms and transmission dynamics.
Abstract
The World Health Organization has identified ST23 carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) as a critical public health threat. Through China's national surveillance system (BRICS), we identified and characterized ST23 CR-hvKP bloodstream isolates from 2019-2023. Among 1069 CRKP bloodstream isolates, four ST23-K1 strains (0.37%) were detected across two hospitals, including a nosocomial transmission pair (differing by only 2 core SNPs). Clinical outcomes revealed that three of the four patients achieved recovery following appropriate antibiotic therapy, with one mortality case attributed to underlying comorbidities. All four ST23 isolates demonstrated resistance to multiple antibiotics, indicating a pattern of multidrug resistance. Genomic analysis uncovered diverse resistance mechanisms: the nosocomial transmission pair possessed conjugative IncFIIK2 NDM-1 plasmids, while the others harbored conjugative IncFIIK34 KPC-2 plasmids, which exhibited reduced carbapenem resistance attributed to the downregulation of blaKPC-2 expression. Conjugation assays revealed high transferability (10-5 for IncFIIK2 NDM-1; 10-4 for IncFIIK34 KPC-2). Whole-plasmid comparative genomics analysis suggested that the IncFIIK2 NDM-1 plasmids shared > 99% identity with historical IncFIIK2 plasmid backbones from Chinese K. pneumoniae isolates (2014-2022), suggesting local evolution. Notably, only 4.4% (26/590) of global IncFIIK2 plasmids carried blaNDM-1 and all IncFIIK2 NDM-1 plasmids maintain conjugative potential. All strains harbored conserved virulence plasmids and maintained hypervirulence, as indicated by a mouse infection model, with the exception of one strain that exhibited cps mutations. This study reports the first genomic evidence of a high-frequency conjugative IncFIIK2 NDM-1 plasmid in a hospital-transmitted ST23 CR-hvKP clone, highlighting the need for plasmid-focused surveillance to control this potential threat.
Background
The study addresses the public health threat posed by ST23 carbapenem-resistant hypervirulent Klebsiella pneumoniae, which has been recognized by the World Health Organization. Prior knowledge indicated that this pathogen exhibits multidrug resistance and poses significant risks in healthcare settings. This research is critical as it provides genomic insights into the transmission dynamics and resistance mechanisms of this strain.
Methods
The study utilized China's national surveillance system (BRICS) to identify and characterize ST23 CR-hvKP bloodstream isolates from 2019 to 2023. A total of 1069 CRKP bloodstream isolates were analyzed, with a focus on four identified ST23-K1 strains. The study employed genomic analysis and conjugation assays to assess resistance mechanisms and plasmid transferability.
Results
Among 1069 CRKP bloodstream isolates, four ST23-K1 strains (0.37%) were detected. Three of the four patients achieved recovery following appropriate antibiotic therapy, while one case resulted in mortality due to underlying comorbidities. The conjugation assays indicated high transferability rates of the plasmids, with 10^-5 for IncFII_K2 NDM-1 and 10^-4 for IncFII_K34 KPC-2.
Interpretation
The findings suggest a concerning trend in the transmission of hypervirulent strains of Klebsiella pneumoniae, particularly with the identified plasmids. While the study presents statistically significant data regarding plasmid transferability, the clinical significance of these findings remains uncertain due to the small sample size and lack of broader clinical context. The reliance on genomic analysis may limit the applicability of results to real-world clinical scenarios.
Key findings
- 0.37% ST23-K1 strains detected among 1069 CRKP bloodstream isolates.
- Three of the four patients achieved recovery following appropriate antibiotic therapy.
- One mortality case attributed to underlying comorbidities.
- Conjugation assays revealed high transferability (10^-5 for IncFII_K2 NDM-1; 10^-4 for IncFII_K34 KPC-2).
- > 99% identity with historical IncFII_K2 plasmid backbones from Chinese K. pneumoniae isolates (2014-2022).
- Only 4.4% (26/590) of global IncFII_K2 plasmids carried bla_NDM-1.
Limitations
- small n=4 for ST23 strains identified
- reliance on genomic analysis without clinical trials
- observational study design limits causal inference
- short follow-up period for clinical outcomes