Medical News: Scientists Warn Of Nosocomial Infections Rising In China Involving Klebsiella Pneumoniae With Hypervirulence And Carbapenem Resistance

Medical News: Medical researchers at the Chinese Academy of Medical Sciences and Peking Union Medical College have raised a red flag about a growing public health concern in China - the surge in nosocomial infections involving a hybrid strain of Klebsiella pneumoniae, known as Carbapenem-Resistant Hypervirulent K. pneumoniae (CR-hvKP). Historically, Klebsiella pneumoniae has been classified into two distinct types: Classic K. pneumoniae (cKP) and Hypervirulent K. pneumoniae (hvKP). cKP typically affects immunocompromised patients, while hvKP leads to fatal community-acquired infections such as pyogenic liver abscess, endophthalmitis, and meningitis. However, both these types have recently converged, giving rise to the emergence of CR-hvKP, a multidrug-resistant, hypervirulent, and highly transmissible pathogen that poses a significant challenge to public health, particularly in clinical settings across Asia, with China reporting the majority of cases.


 
Antimicrobial Resistance Mechanisms
According to recent Medical News updates, carbapenem-resistant K. pneumoniae (CRKP) strains have become a predominant concern in Chinese healthcare settings, constituting approximately 90% of clinical carbapenem-resistant Enterobacteriaceae (CRE) infections.
 
The widespread use of antimicrobials has provided CRKP strains with a selective advantage. Notably, the alarming development of CR-hvKP occurs when either hvKP or CRKP acquires plasmids carrying the carbapenem-resistance gene or the virulence gene. Alternatively, classic K. pneumoniae (cKP) may acquire a hybrid plasmid containing both genes. This convergence of hypervirulence and carbapenem resistance presents a daunting challenge, as CR-hvKP exhibits devastating clinical outcomes.
 
Virulence Factors of CR-hvKP
Understanding the virulence factors of CR-hvKP is crucial in comprehending its pathogenicity. The hypermucoviscosity (HMV) phenotype, characterized by a thick capsule, is a key factor contributing to the virulence of hvKP. The capsule acts as a physical barrier, hindering the transfer of genes, and strains with hypercapsules are less prone to harboring antimicrobial resistant genes. Notably, the capsular serotypes K1 and K2 are highly prevalent in hvKP and are associated with invasive infectious diseases.
 
Siderophores, crucial for bacterial metabolic activities, play a significant role in CR-hvKP's virulence. Compared to cKP isolates, hvKP isolates produce more siderophores, with aerobactin being the predominant contributor to hypervirulence. The regulatory mechanism of siderophores in hvKP involves a complex interplay of iron availability, iron-responsive regulators, and two-component systems, ensuring efficient iron scavenging from the host environment.
 
Virulence plasmids and a mobile genetic element called ICEKp contribute to the dissemination of virulence factors in CR-hvKP. Virulence plasmids often carry genes related to hypermucoviscosity, siderophore production, and resistance to metals. Additionally, ICEKp, with its various types, facilitates the horizontal transfer of virulence-associated genes among K. pneumoniae strains.
 
Other virulence factors, such as type 1/3 fimbriae, outer membrane proteins (OMPs), and the type 6 secret ion system (T6SS), further enhance the pathogenicity of CR-hvKP. These factors play roles in adhesion, antibiotic resistance, and survival in different microenvironments during infection.
 
Clinical Impacts of CR-hvKP
The clinical presentations of CR-hvKP are diverse, ranging from pyogenic liver abscesses, endophthalmitis, and meningitis to hospital-acquired urinary tract infections, pneumonia, septicemias, and soft tissue infections. CR-hvKP is associated with high morbidity and mortality, leading to poor clinical outcomes. Notably, it poses a unique challenge due to its ability to simultaneously exhibit clinical signs of both CRKP and hvKP infections.
 
Patients with underlying comorbidities, such as diabetes mellitus, are at a higher risk of CR-hvKP infection. The clinical outcomes are often adverse, with high mortality rates, particularly in cases of bloodstream infections (BSI). Metastatic complications, affecting organs such as the kidneys, spleen, prostate, and scrotum, further contribute to the complexity of CR-hvKP infections.
 
Epidemiology and Genetic Backgrounds
China has been identified as the epicenter of the CR-hvKP epidemic, with a significant rise in reported cases since 2012. The prevalence varies across regions, with Zhejiang, Jiangsu, and Beijing reporting the highest incidence. The predominant carbapenem-resistance determinant in CR-hvKP is the blaKPC-2 gene, accounting for the majority of cases. The ST11-KL64 type is the most common clone, followed by ST23 and ST15. Notably, the shift from KL47 to KL64 in ST11 CRKP strains has been observed, indicating a dynamic evolution in virulence and resistance mechanisms.
 
Conclusion
The emergence of CR-hvKP in China poses a severe threat to public health, necessitating urgent attention and comprehensive strategies for containment. The convergence of hypervirulence and carbapenem resistance is driven by the acquisition of plasmids carrying crucial genes, highlighting the role of horizontal gene transfer in the evolution of this multidrug-resistant pathogen.
 
Understanding the molecular mechanisms behind the virulence and resistance of CR-hvKP is crucial for effective surveillance and management.
 
Efforts should focus on developing strategies to curb the proliferation of K. pneumoniae virulence plasmids and combat carbapenem resistance in China. The high morbidity and mortality associated with CR-hvKP infections underscore the need for enhanced infection control measures, robust surveillance systems, and the development of novel treatment options to tackle this emerging healthcare threat. Continued research into the epidemiology, genetic backgrounds, and clinical impacts of CR-hvKP is imperative to stay ahead of this evolving public health challenge.
 
The study findings were published in the peer reviewed journal: Science Bulletin.
https://www.sciencedirect.com/science/article/pii/S2095927323006758
 
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