Antimicrobial resistance of hypervirulent Klebsiella pneumoniae

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The exact definition of hvKP is a controversial issue. Although the string test is generally accepted as a method for determining hvKP, many cases of string test-positive K. pneumoniae isolates do not exhibit hypervirulence. Several virulence factors, such as the K1/K2 serotypes, RmpA, and aerobactin, seem to be associated strongly with the hypervirulence of hvKP. Therefore, the exact phenotypic and genotypic definitions of hvKP need to be established firmly. The predominant hvKP clone is ST23, and most ST23 clones have the K1 serotype. The reason for this also remains unclear. It is interesting that the predominant clone of carbapenem-resistant cKP (classic Klebsiella pneumoniae), ST258, is not the predominant clone of hvKP. Additional studies analyzing epidemiological and pathogenic characteristics of each clone are required to understand the exact relationship between the specific clones and specific phenotypes of K. pneumoniae, such as hypervirulence or antibiotic resistance. The threat of hvKP acquiring carbapenem resistance is becoming a reality in certain countries, such as China, where both carbapenem-resistant cKP and carbapenem-susceptible hvKP strains are prevalent. The prevalence of hvKP among carbapenem-resistant K. pneumoniae isolates in China is high, ranging from 7.4% to 15%. The epidemiology of carbapenem-resistant hvKP in China implies the possibility of the transmission of mobile genetic elements between hvKP and cKP strains. Until now, ST11 and ST23 have been identified as the major clones of carbapenem-resistant hvKP strains in China. In China, ST11 and ST23 are the major clones of cKP and hvKP strains, respectively. Additionally, KPC-2 is found in 94.4% of carbapenem-resistant hvKP isolates in China. KPC-2 is the most prevalent carbapenemase in China. These results also imply the transfer of mobile genetic elements between hvKP and cKP strains. A recent study using genomic analyses showed that ST11 carbapenem-resistant cKP strains could become carbapenem-resistant hvKP strains through the acquisition of the pLVPK-like plasmid. Therefore, an immediate response to the global emergence of hvKP with resistance determinants, especially against carbapenems, is required. In conclusion, great knowledge gaps exist for hvKP, despite a great deal of clinical, physiological, and pathogenic studies of hvKP over the past 30-years. The definition of hvKP remains unclear. Hypervirulence-associated determinants of hvKP require further study. These hypervirulence-associated factors may become a good target for the development of novel therapeutic agents. Epidemiological analysis of recent hvKP clinical isolates in China indicates a potential for the global dissemination of hvKP strains with extensive antibiotic resistances in the near future. The development of effective diagnostic tools for identification of hvKP is required for the effective control of hvKP in the clinical field. The development of novel antimicrobial agents also is absolutely required.

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