Review Article

Molecular epidemiology of hypervirulent Klebsiella pneumoniae: a systematic review and meta-analysis


Classical (CKp) and hypervirulent (hvKp) Klebsiella pneumoniae are two different circulating pathotypes. The aim of this study was to assess the prevalence, epidemiology and molecular relatedness of hvKps using a systemic review and meta-analysis. The data extracted from Medline, Embase, and Web of Science and finally 14 studies met the eligible criteria. To combine prevalence proportions of all studies, we performed the metaprop command embedded in the Meta package software. Totally, of 1814 K. pneumoniae isolates, 21.7% (394/1814) were hvKp. The molecular typing showed that all hvKp isolates were grouped into 50 different sequence types (STs) of them ST23, ST11, ST65 and ST86 were common. K1, K2 and K64 were dominant capsule serotypes that strongly related to ST23, ST65 and ST11, respectively. It seems that clonal group 23 (CG23) is associated with liver abscess and CG11 related to various clinical sources.

1. Liu C, Guo J. Hypervirulent Klebsiella pneumoniae (hypermucoviscous and aerobactin positive) infection over 6 years in the elderly in China: antimicrobial resistance patterns, molecular epidemiology and risk factor. Ann Clin Microbiol Antimicrob 2019;18:4.
2. Sellick JA, Russo TA. Getting hypervirulent Klebsiella pneumoniae on the radar screen. Curr Opin Infect Dis 2018;31:341-346.
3. Lee C-R, Lee JH, Park KS, Jeon JH, Kim YB, Cha C-J, et al. Antimicrobial resistance of hypervirulent Klebsiella pneumoniae: epidemiology, hypervirulence-associated determinants, and resistance mechanisms. Front Cell Infect Microbiol 2017;7:483.
4. Zhang Y, Zeng J, Liu W, Zhao F, Hu Z, Zhao C, et al. Emergence of a hypervirulent carbapenem-resistant Klebsiella pneumoniae isolate from clinical infections in China. J Infect 2015;71:553-560.
5. Tabrizi A, Badmasti F, Shahcheraghi F, Azizi O. Outbreak of hypervirulent Klebsiella pneumoniae harbouring blaVIM-2 among mechanically-ventilated drug-poisoning patients with high mortality rate in Iran. J Glob Antimicrob Resist 2018;15:93-98.
6. Russo TA, Olson R, Fang C-T, Stoesser N, Miller M, MacDonald U, et al. Identification of biomarkers for differentiation of hypervirulent Klebsiella pneumoniae from classical K. pneumoniae. J Clin Microbiol 2018;56(9):e00776-18.
7. Li G, Sun S, Zhao ZY, Sun Y. The pathogenicity of rmpA or aerobactin-positive Klebsiella pneumoniae in infected mice. J Int Med Res 2019;47:4344-4352.
8. Shi Q, Lan P, Huang D, Hua X, Jiang Y, Zhou J, et al. Diversity of virulence level phenotype of hypervirulent Klebsiella pneumoniae from different sequence type lineage. BMC Microbiol 2018;18:94.
9. Remya P, Shanthi M, Sekar U. Occurrence and characterization of hyperviscous K1 and K2 serotype in Klebsiella pneumoniae. J Lab Physicians 2018;10:283-288.
10. Ma Y, Bao C, Liu J, Hao X, Cao J, Ye L, et al. Microbiological characterisation of Klebsiella pneumoniae isolates causing bloodstream infections from five tertiary hospitals in Beijing, China. J Glob Antimicrob Resist 2018;12:162-166.
11. Catalán-Nájera JC, Garza-Ramos U, Barrios-Camacho H. Hypervirulence and hypermucoviscosity: two different but complementary Klebsiella spp. phenotypes? Virulence 2017;8:1111-1123.
12. Yu F, Lv J, Niu S, Du H, Tang Y-W, Bonomo RA, et al. In vitro activity of ceftazidime-avibactam against carbapenem-resistant and hypervirulent Klebsiella pneumoniae isolates. Antimicrob Agents Chemother 2018;62 (8):e01031-1018.
13. Russo TA, Olson R, MacDonald U, Metzger D, Maltese LM, Drake EJ, et al. Aerobactin mediates virulence and accounts for increased siderophore production under iron-limiting conditions by hypervirulent (hypermucoviscous) Klebsiella pneumoniae. Infect Immun 2014;82:2356-2367.
14. Bailey DC, Alexander E, Rice MR, Drake EJ, Mydy LS, Aldrich CC, et al. Structural and functional delineation of aerobactin biosynthesis in hypervirulent Klebsiella pneumoniae. J Biol Chem 2018;293:7841-7852.
15. Balduzzi S, Rücker G, Schwarzer G. How to perform a meta-analysis with R: a practical tutorial. Evidence-based mental health. Evid Based Ment Health 2019; 22:153-160.
16. Stijnen T, Hamza TH, Özdemir P. Random effects meta‐analysis of event outcome in the framework of the generalized linear mixed model with applications in sparse data. Stat Med 2010; 29:3046-3067.
17. Bengoechea JA, Sa Pessoa J. Klebsiella pneumoniae infection biology: living to counteract host defences. FEMS Microbiol Rev 2019;43:123-144.
18. Rajabnia R, Asgharpour F, Shahandashti EF, Moulana Z. Nosocomial emerging of (VIM1) carbapenemase-producing isolates of Klebsiella pneumoniae in North of Iran. Iran J Microbiol 2015;7:88-93.
19. Ye M, Tu J, Jiang J, Bi Y, You W, Zhang Y, et al. Clinical and genomic analysis of liver abscess-causing Klebsiella pneumoniae identifies new liver abscess-associated virulence genes. Front Cell Infect Microbiol 2016;6:165.
20. Ko KS, Lee J-Y, Baek JY, Suh J-Y, Lee MY, Choi JY, et al. Predominance of an ST11 extended-spectrum β-lactamase-producing Klebsiella pneumoniae clone causing bacteraemia and urinary tract infections in Korea. J Med Microbiol 2010;59:822-828.
21. Dong N, Yang X, Zhang R, Chan EW-C, Chen S. Tracking microevolution events among ST11 carbapenemase-producing hypervirulent Klebsiella pneumoniae outbreak strains. Emerg Microbes Infect 2018;7:146.
22. Yeh K-M, Chiu S-K, Lin C-L, Huang L-Y, Tsai Y-K, Chang J-C, et al. Surface antigens contribute differently to the pathophysiological features in serotype K1 and K2 Klebsiella pneumoniae strains isolated from liver abscesses. Gut Pathog 2016;8:4.
23. Lee IR, Molton JS, Wyres KL, Gorrie C, Wong J, Hoh CH, et al. Differential host susceptibility and bacterial virulence factors driving Klebsiella liver abscess in an ethnically diverse population. Sci Rep 2016;6:29316.
24. Aghamohammad S, Badmasti F, Solgi H, Aminzadeh Z, Khodabandelo Z, Shahcheraghi F. First report of extended-spectrum betalactamase-producing Klebsiella pneumoniae among fecal carriage in Iran: high diversity of clonal relatedness and virulence factor profiles. Microb Drug Resist 2020;26:261-269.
25. Bialek-Davenet S, Criscuolo A, Ailloud F, Passet V, Jones L, Delannoy-Vieillard A-S, et al. Genomic definition of hypervirulent and multidrug-resistant Klebsiella pneumoniae clonal groups. Emerg Infect Dis 2014;20:1812-1820.
26. Zhang Y, Jin L, Ouyang P, Wang Q, Wang R, Wang J, et al. Evolution of hypervirulence in carbapenem-resistant Klebsiella pneumoniae in China: a multicentre, molecular epidemiological analysis. J Antimicrob Chemother 2020;75:327-336.
27. Zhan L, Wang S, Guo Y, Jin Y, Duan J, Hao Z, et al. Outbreak by hypermucoviscous Klebsiella pneumoniae ST11 isolates with carbapenem resistance in a tertiary hospital in China. Front Cell Infect Microbiol 2017;7:182.
28. Harada S, Aoki K, Yamamoto S, Ishii Y, Sekiya N, Kurai H, et al. Clinical and molecular characteristics of Klebsiella pneumoniae isolates causing bloodstream infections in Japan: occurrence of hypervirulent infections in health care. J Clin Microbiol 2019;57(11):e01206-19.
29. Struve C, Roe CC, Stegger M, Stahlhut SG, Hansen DS, Engelthaler DM, et al. Mapping the evolution of hypervirulent Klebsiella pneumoniae. mBio 2015;6 (4):e00630.
30. Zhao J, Chen J, Zhao M, Qiu X, Chen X, Zhang W, et al. Multilocus sequence types and virulence determinants of hypermucoviscosity-positive Klebsiella pneumoniae isolated from community-acquired infection cases in Harbin, North China. Jpn J Infect Dis 2016;69:357-360.
31. Luo Y, Wang Y, Ye L, Yang J. Molecular epidemiology and virulence factors of pyogenic liver abscess causing Klebsiella pneumoniae in China. Clin Microbiol Infect 2014;20: O818-824.
32. Yan Q, Zhou M, Zou M, Liu W-e. Hypervirulent Klebsiella pneumoniae induced ventilator-associated pneumonia in mechanically ventilated patients in China. Eur J Clin Microbiol Infect Dis 2016;35:387-396.
33. Fu L, Huang M, Zhang X, Yang X, Liu Y, Zhang L, et al. Frequency of virulence factors in high biofilm formation blaKPC-2 producing Klebsiella pneumoniae strains from hospitals. Microb Pathog 2018;116:168-172.
34. Ku Y-H, Chuang Y-C, Chen C-C, Lee M-F, Yang Y-C, Tang H-J, et al. Klebsiella pneumoniae isolates from meningitis: epidemiology, virulence and antibiotic resistance. Sci Rep 2017;7:6634.
35. Jung S, Chae H, Park Y, Yu J, Kim S, Lee H, et al. Microbiological and clinical characteristics of bacteraemia caused by the hypermucoviscosity phenotype of Klebsiella pneumoniae in Korea. Epidemiol Infect 2013;141:334-340.
36. Zhao Y, Zhang X, Torres VVL, Liu H, Rocker A, Zhang Y, et al. An outbreak of carbapenem-resistant and hypervirulent Klebsiella pneumoniae in an intensive care unit of a major teaching hospital in Wenzhou, China. Front Public Health 2019;7:229.
37. Rossi B, Gasperini ML, Leflon-Guibout V, Gioanni A, de Lastours V, Rossi G, et al. Hypervirulent Klebsiella pneumoniae in cryptogenic liver abscesses, Paris, France. Emerg Infect Dis 2018;24:221-229.
IssueVol 13 No 3 (2021) QRcode
SectionReview Article(s)
Hypervirulent Klebsiella pneumonia; Virulence factors; Molecular typing; Pathotypesi genotypes

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Sanikhani R, Moeinirad M, Shahcheraghi F, Lari A, Fereshteh S, Sepehr A, Salimi A, Badmasti F. Molecular epidemiology of hypervirulent Klebsiella pneumoniae: a systematic review and meta-analysis. Iran J Microbiol. 2021;13(3):257-265.