Clinical and phenotypic differences between classic and hypervirulent Klebsiella pneumonia: an emerging and under-recognized pathogenic variant

  • D. K. Pomakova
  • C-B. Hsiao
  • J. M. Beanan
  • R. Olson
  • U. MacDonald
  • Y. Keynan
  • T. A. RussoEmail author


The purpose of this study was to increase awareness, gain insight into acquisition, and assess the virulence of the hypervirulent (hypermucoviscous) clinical variant (hvKP) that is entrenched in the Pacific Rim but emerging in Western countries. A case of community-acquired liver abscess with metastatic spread to the spleen is described. Comparative in vitro and in vivo virulence studies on this isolate (hvKP1) and four randomly chosen blood isolates of “classic” K. pneumonia strains (cKP1-4) were performed. Cases of hvKP infection are occurring in Western countries and are under-recognized. A hypermucoviscous phenotype is a surrogate laboratory marker for this variant. The propensity of hvKP strains for metastatic spread in non-compromised hosts is both a defining and unusual trait. The mode of acquisition in the described case was unclear but potential means are discussed. hvKP1 was more resistant to complement and neutrophil-mediated bactericidal activity and was more virulent in a rat subcutaneous abscess model than cKP1-4. Recognition of the hypermucoviscous phenotype, defined by a positive “string-test”, will alert the microbiologist or clinician that the infecting strain may be a hvKP, which is hypervirulent compared to cKP. This will improve our understanding of the epidemiology and clinical spectrum of infection, which may be more extensive than appreciated.


Liver Abscess Metastatic Spread Pyogenic Liver Abscess Splenic Abscess Subdural Empyema 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank the Clinical Microbiology laboratories at Erie County Medical Center and the Veterans Administration Western New York Healthcare System for their sage advice and support. This work was supported in part by the National Institutes of Health grant 1RZ1 AI 088318-01 AI (TAR) and by a Merit Review grant from the Department of Veterans Affairs (TAR).


  1. 1.
    Ko WC, Paterson DL, Sagnimeni AJ et al (2002) Community-acquired Klebsiella pneumoniae bacteremia: global differences in clinical patterns. Emerg Infect Dis 8(2):160–166PubMedCrossRefGoogle Scholar
  2. 2.
    Moellering RC Jr (2010) NDM-1–a cause for worldwide concern. N Engl J Med 363(25):2377–2379PubMedCrossRefGoogle Scholar
  3. 3.
    Fung CP, Chang FY, Lee SC et al (2002) A global emerging disease of Klebsiella pneumoniae liver abscess: is serotype K1 an important factor for complicated endophthalmitis? Gut 50(3):420–424PubMedCrossRefGoogle Scholar
  4. 4.
    Keynan Y, Karlowsky JA, Walus T et al (2007) Pyogenic liver abscess caused by hypermucoviscous Klebsiella pneumoniae. Scand J Infect Dis 39(9):828–830PubMedCrossRefGoogle Scholar
  5. 5.
    Lederman ER, Crum NF (2005) Pyogenic liver abscess with a focus on Klebsiella pneumoniae as a primary pathogen: an emerging disease with unique clinical characteristics. Am J Gastroenterol 100(2):322–331PubMedCrossRefGoogle Scholar
  6. 6.
    McCabe R, Lambert L, Frazee B (2010) Invasive Klebsiella pneumoniae infections, California, USA. Emerg Infect Dis 16(9):1490–1491PubMedCrossRefGoogle Scholar
  7. 7.
    Turton JF, Englender H, Gabriel SN et al (2007) Genetically similar isolates of Klebsiella pneumoniae serotype K1 causing liver abscesses in three continents. J Med Microbiol 56(Pt 5):593–597PubMedCrossRefGoogle Scholar
  8. 8.
    Chang FY, Chou MY (1995) Comparison of pyogenic liver abscesses caused by Klebsiella pneumoniae and non-K. pneumoniae pathogens. J Formos Med Assoc 94(5):232–237PubMedGoogle Scholar
  9. 9.
    Cheng DL, Liu YC, Yen MY et al (1991) Septic metastatic lesions of pyogenic liver abscess. Their association with Klebsiella pneumoniae bacteremia in diabetic patients. Arch Intern Med 151(8):1557–1559PubMedCrossRefGoogle Scholar
  10. 10.
    Dylewski JS, Dylewski I (1998) Necrotizing fasciitis with Klebsiella liver abscess. Clin Infect Dis 27(6):1561–1562PubMedCrossRefGoogle Scholar
  11. 11.
    Fang CT, Lai SY, Yi WC et al (2007) Klebsiella pneumoniae genotype K1: an emerging pathogen that causes septic ocular or central nervous system complications from pyogenic liver abscess. Clin Infect Dis 45(3):284–293PubMedCrossRefGoogle Scholar
  12. 12.
    Han SH (1995) Review of hepatic abscess from Klebsiella pneumoniae. An association with diabetes mellitus and septic endophthalmitis. West J Med 162(3):220–224PubMedGoogle Scholar
  13. 13.
    Liu YC, Cheng DL, Lin CL (1986) Klebsiella pneumoniae liver abscess associated with septic endophthalmitis. Arch Intern Med 146(10):1913–1916PubMedCrossRefGoogle Scholar
  14. 14.
    Wang JH, Liu YC, Lee SS et al (1998) Primary liver abscess due to Klebsiella pneumoniae in Taiwan. Clin Infect Dis 26(6):1434–1438PubMedCrossRefGoogle Scholar
  15. 15.
    Fang CT, Chen YC, Chang SC et al (2000) Klebsiella pneumoniae meningitis: timing of antimicrobial therapy and prognosis. QJM 93(1):45–53PubMedCrossRefGoogle Scholar
  16. 16.
    Ku YH, Chuang YC, Yu WL (2008) Clinical spectrum and molecular characteristics of Klebsiella pneumoniae causing community-acquired extrahepatic abscess. J Microbiol Immunol Infect 41(4):311–317PubMedGoogle Scholar
  17. 17.
    Russo TA, MacDonald U, Beanan JM et al (2009) Penicillin-binding protein 7/8 contributes to the survival of Acinetobacter baumannii in vitro and in vivo. J Infect Dis 199(4):513–521PubMedCrossRefGoogle Scholar
  18. 18.
    Russo TA, Beanan JM, Olson R et al (2008) Rat pneumonia and soft-tissue infection models for the study of Acinetobacter baumannii biology. Infect Immun 76(8):3577–3586PubMedCrossRefGoogle Scholar
  19. 19.
    Nazareth H, Genagon SA, Russo TA (2007) Extraintestinal pathogenic Escherichia coli survives within neutrophils. Infect Immun 75(6):2776–2785PubMedCrossRefGoogle Scholar
  20. 20.
    Dalhoff A, Frank G, Luckhaus G (1982) The granuloma pouch: an in vivo model for pharmacokinetic and chemotherapeutic investigations. I. Biochemical and histological characterization. Infection 10(6):354–360PubMedCrossRefGoogle Scholar
  21. 21.
    Dalhoff A, Frank G, Luckhaus G (1983) The granuloma pouch: an in vivo model for pharmacokinetic and chemotherapeutic investigations. II. Microbiological characterization. Infection 11(1):41–46PubMedCrossRefGoogle Scholar
  22. 22.
    Russo TA, Liang Y, Cross AS (1994) The presence of K54 capsular polysaccharide increases the pathogenicity of Escherichia coli in vivo. J Infect Dis 169(1):112–118PubMedCrossRefGoogle Scholar
  23. 23.
    Nassif X, Fournier JM, Arondel J et al (1989) Mucoid phenotype of Klebsiella pneumoniae is a plasmid-encoded virulence factor. Infect Immun 57(2):546–552PubMedGoogle Scholar
  24. 24.
    Russo TA, Beanan JM, Olson R et al (2007) A killed, genetically engineered derivative of a wild-type extraintestinal pathogenic E. coli strain is a vaccine candidate. Vaccine 25(19):3859–3870PubMedCrossRefGoogle Scholar
  25. 25.
    Lee WS, Choi ST, Kim KK (2011) Splenic abscess: a single institution study and review of the literature. Yonsei Med J 52(2):288–292PubMedCrossRefGoogle Scholar
  26. 26.
    Tu YC, Lu MC, Chiang MK et al (2009) Genetic requirements for Klebsiella pneumoniae-induced liver abscess in an oral infection model. Infect Immun 77(7):2657–2671PubMedCrossRefGoogle Scholar
  27. 27.
    Kumarasamy KK, Toleman MA, Walsh TR et al (2010) Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis 10(9):597–602PubMedCrossRefGoogle Scholar
  28. 28.
    Laupland KB, Church DL, Vidakovich J et al (2008) Community-onset extended-spectrum beta-lactamase (ESBL) producing Escherichia coli: importance of international travel. J Infect 57(6):441–448PubMedCrossRefGoogle Scholar
  29. 29.
    Nagano N, Cordevant C, Nagano Y (2008) Upper and lower urinary tract infection caused by Klebsiella pneumoniae serotype K2 and CTX-M-15 beta-lactamase-producing serotype K1: a case report and characterization of serum killing resistance. J Med Microbiol 57(Pt 1):121–124PubMedCrossRefGoogle Scholar
  30. 30.
    Lee HC, Chuang YC, Yu WL et al (2006) Clinical implications of hypermucoviscosity phenotype in Klebsiella pneumoniae isolates: association with invasive syndrome in patients with community-acquired bacteraemia. J Intern Med 259(6):606–614PubMedCrossRefGoogle Scholar
  31. 31.
    Jang TN, Wang FD, Wang LS et al (1993) Gram-negative bacillary meningitis in adults: a recent six-year experience. J Formos Med Assoc 92(6):540–546PubMedGoogle Scholar
  32. 32.
    Lu CH, Chang WN, Wu HS (1997) Klebsiella pneumoniae meningitis: analysis on clinical features of thirty-two adult patients. Zhonghua Yi Xue Za Zhi (Taipei) 60(6):296–302Google Scholar
  33. 33.
    Tang LM, Chen ST, Hsu WC et al (1997) Klebsiella meningitis in Taiwan: an overview. Epidemiol Infect 119(2):135–142PubMedCrossRefGoogle Scholar
  34. 34.
    Fang CT, Chuang YP, Shun CT et al (2004) A novel virulence gene in Klebsiella pneumoniae strains causing primary liver abscess and septic metastatic complications. J Exp Med 199(5):697–705PubMedCrossRefGoogle Scholar
  35. 35.
    Brisse S, Fevre C, Passet V et al (2009) Virulent clones of Klebsiella pneumoniae: identification and evolutionary scenario based on genomic and phenotypic characterization. PLoS ONE 4(3):e4982PubMedCrossRefGoogle Scholar
  36. 36.
    Yeh KM, Kurup A, Siu LK et al (2007) Capsular serotype K1 or K2, rather than magA and rmpA, is a major virulence determinant for Klebsiella pneumoniae liver abscess in Singapore and Taiwan. J Clin Microbiol 45(2):466–471PubMedCrossRefGoogle Scholar
  37. 37.
    Yu WL, Ko WC, Cheng KC et al (2008) Comparison of prevalence of virulence factors for Klebsiella pneumoniae liver abscesses between isolates with capsular K1/K2 and non-K1/K2 serotypes. Diagn Microbiol Infect Dis 62(1):1–6PubMedCrossRefGoogle Scholar
  38. 38.
    Yu WL, Ko WC, Cheng KC et al (2006) Association between rmpA and magA genes and clinical syndromes caused by Klebsiella pneumoniae in Taiwan. Clin Infect Dis 42(10):1351–1358PubMedCrossRefGoogle Scholar
  39. 39.
    Chen YT, Chang HY, Lai YC et al (2004) Sequencing and analysis of the large virulence plasmid pLVPK of Klebsiella pneumoniae CG43. Gene 337:189–198PubMedCrossRefGoogle Scholar
  40. 40.
    Clements A, Gaboriaud F, Duval JF et al (2008) The major surface-associated saccharides of Klebsiella pneumoniae contribute to host cell association. PLoS ONE 3(11):e3817PubMedCrossRefGoogle Scholar
  41. 41.
    Merino S, Camprubi S, Alberti S et al (1992) Mechanisms of Klebsiella pneumoniae resistance to complement-mediated killing. Infect Immun 60(6):2529–2535PubMedGoogle Scholar
  42. 42.
    Mizuta K, Ohta M, Mori M et al (1983) Virulence for mice of Klebsiella strains belonging to the O1 group: relationship to their capsular (K) types. Infect Immun 40(1):56–61PubMedGoogle Scholar
  43. 43.
    Simoons-Smit AM, Verweij-van Vught AM, MacLaren DM (1986) The role of K antigens as virulence factors in Klebsiella. J Med Microbiol 21(2):133–137PubMedCrossRefGoogle Scholar
  44. 44.
    Simoons-Smit AM, Verwey-van Vught AM, Kanis IY et al (1984) Virulence of Klebsiella strains in experimentally induced skin lesions in the mouse. J Med Microbiol 17(1):67–77PubMedCrossRefGoogle Scholar
  45. 45.
    Yeh KM, Chang FY, Fung CP et al (2006) magA is not a specific virulence gene for Klebsiella pneumoniae strains causing liver abscess but is part of the capsular polysaccharide gene cluster of K. pneumoniae serotype K1. J Med Microbiol 55(Pt 6):803–804PubMedCrossRefGoogle Scholar
  46. 46.
    Nassif X, Sansonetti PJ (1986) Correlation of the virulence of Klebsiella pneumoniae K1 and K2 with the presence of a plasmid encoding aerobactin. Infect Immun 54(3):603–608PubMedGoogle Scholar
  47. 47.
    Wu KM, Li LH, Yan JJ et al (2009) Genome sequencing and comparative analysis of Klebsiella pneumoniae NTUH-K2044, a strain causing liver abscess and meningitis. J Bacteriol 191(14):4492–4501PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • D. K. Pomakova
    • 1
    • 2
  • C-B. Hsiao
    • 3
    • 4
  • J. M. Beanan
    • 2
    • 5
  • R. Olson
    • 2
    • 5
  • U. MacDonald
    • 2
    • 5
  • Y. Keynan
    • 6
  • T. A. Russo
    • 1
    • 2
    • 4
    • 5
    • 7
    Email author
  1. 1.Veterans Administration Western New York Healthcare SystemBuffaloUSA
  2. 2.Department of MedicineUniversity at Buffalo-State University of New YorkBuffaloUSA
  3. 3.Erie County Medical CenterErieUSA
  4. 4.Department of Microbiology and ImmunologyUniversity at Buffalo-State University of New YorkBuffaloUSA
  5. 5.The Witebsky Center for Microbial PathogenesisUniversity at Buffalo-State University of New YorkBuffaloUSA
  6. 6.Department of Medical MicrobiologyUniversity of ManitobaWinnipegCanada
  7. 7.Department of Medicine, Division of Infectious DiseasesUniversity at Buffalo-State University of New YorkBuffaloUSA

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