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Review

Hypervirulent Klebsiella pneumoniae

Thomas A. Russo, Candace M. Marr
Thomas A. Russo
aDepartment of Medicine, University at Buffalo-State University of New York, Buffalo, New York, USA
bDepartment of Microbiology and Immunology, University at Buffalo-State University of New York, Buffalo, New York, USA
cThe Witebsky Center for Microbial Pathogenesis, University at Buffalo-State University of New York, Buffalo, New York, USA
dThe Veterans Administration Western New York Healthcare System, Buffalo, New York, USA
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Candace M. Marr
aDepartment of Medicine, University at Buffalo-State University of New York, Buffalo, New York, USA
eErie County Medical Center, Buffalo, New York, USA
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DOI: 10.1128/CMR.00001-19
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  • FIG 1
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    FIG 1

    Schematic representation of the hvKp virulence plasmid pLVPK (red circle, 219,385 bp) (83) and pVir-CR-HvKp4 (blue circle, 178,154 bp) (22). The locations of various virulence genes and/or biomarkers are marked.

  • FIG 2
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    FIG 2

    An image from an abdominal CT scan of a previously healthy 24-year-old Vietnamese man shows a primary liver abscess (red arrow) with metastatic spread to the spleen (black arrow). (Courtesy of Chiu-Bin Hsaio and Diana Pomakova; reprinted with permission from McGraw-Hill Education [353].)

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    FIG 3

    A previously healthy 33-year-old Chinese male presented with endophthalmitis. (Courtesy of Chiu-Bin Hsaio; reprinted with permission from McGraw-Hill Education [353].)

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  • TABLE 1

    Demographic and clinical features that can assist in differentiating infection due to hypervirulent and classical K. pneumoniae strainsa

    ParameterFinding for pathotype
    hvKpcKp
    Location for the development of infectionMore commonly the communitybMore commonly a health care setting
    HostAll ages; often otherwise healthyOlder, with some form of compromise
    Ethnic backgroundOften Asian, Pacific Islander, HispanicNo ethnic predilection
    Hepatic abscessUsually occurs in the absence of biliary diseaseUsually occurs in the presence of biliary disease
    Number of sites of infectionOften multipleUsually single
    Unusual infectious syndromes for K. pneumoniaeEndophthalmitis, meningitis,c brain abscess, necrotizing fasciitis, splenic abscess, epidural abscessNone
    Copathogens at the site of infectionRare, usually monomicrobialNot uncommon, especially with abdominal, soft tissue, or urinary catheter infection
    • ↵a These are general features; exceptions occur. Definitive diagnosis requires identification of specific biomarkers, but assays for these markers are not presently FDA approved or routinely performed by clinical microbiology laboratories.

    • ↵b With the advent of XDR cKp strains acquiring the hvKp virulence plasmid and thereby the hypervirulent phenotype, an increasing number of hvKp infections are developing in the health care setting; to date, this has been primarily reported from China.

    • ↵c hvKp meningitis occurs in patients with a competent meningeal barrier (as opposed to those with an incompetent meningeal barrier, e.g., neonates or those who have undergone neurosurgery or trauma).

  • TABLE 2

    Major knowledge gaps that exist for hypervirulent K. pneumoniae

    Area of interestKnowledge gap
    EpidemiologyIncidence of infection in various countries
    Prevalence of antimicrobial resistance
    Incidence of health care-associated infections
    Mechanism of acquisition
    PathogenesisMechanism of entry
    Delineation of hvKp-specific virulence genes and mechanism of action
    Mechanism of metastatic spread
    Factors responsible for tissue damage
    Carcinogenic potential
    Host susceptibilityEthnic/genetic predisposition
    TreatmentOptimal approach for source control
    Treatment duration
    Management of endophthamitis, especially for XDR strains
    Role of adjunct therapy
    Infection controlIs there a benefit for implementing infection control measures when a hospitalized patient is infected with an hvKp antimicrobial-sensitive strain on a ward or an ICU?
    Is there a benefit for implementing infection control measures when a hospitalized patient is infected with an hvKp antimicrobial-sensitive strain to protect selected patient groups (e.g., those of certain ethnic backgrounds, such as Asian, or immunocompromised hosts)?
    Is there a benefit of prophylaxis for close contacts?
  • TABLE 3

    Estimated proportion of hvKpa organisms among K. pneumoniae infections in various geographic locales

    SiteTime frameIsolate source/characteristicNo./total (%) of K. pneumoniae infections due to hvKpbReference
    Australia2001–2014Urine3/193 (1.6)28
    Australia2001–2014Mixed clinical (minus urine)19/141 (13.5)28
    Canada (Alberta)2001–2007Community-acquired blood isolates9/134 (6.7)354
    Canada (Quebec)2009–2013Blood isolates1/110 (0.9)17
    China2015ST11, carbapenem resistant11/387 (3)22
    China2008–2012Blood isolates32/70 (46)355
    China2014–2016Carbapenem-resistant isolates32/66 (48.5)311
    China2014–2016Carbapenem-sensitive isolates31/45 (68.9)311
    India2014–2015Urine, respiratory, and blood isolates3/370 (0.8)356
    India2014–2015Carbapenem-resistant blood isolates6/86 (7)357
    Japan2011–2012Sputum and urine isolates22/130 (16.9)133
    Nepal2008–2012Mixed clinical1/131 (0.76)
    Spain (Barcelona)2007–2013Blood isolates37/878 (4.2)139
    UK (Oxford)2008–2011Blood isolates4/69 (5.8)17
    USA (Texas)2009–2010Clinical isolates4/64 (6.3)358
    USA2013Carbapenem-resistant blood isolates0/97 (0)311
    USA2007–2013Urine isolates1/191 (0.5)28
    USA1937–2014Mixed clinical isolates (minus urine)26/490 (5.3)28
    Vietnam2003–2009Mixed clinical isolates16/41 (39)28
    • ↵a Defined by the presence of iuc or rmpA or rmpA2.

    • ↵b Collection bias cannot be excluded.

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Hypervirulent Klebsiella pneumoniae
Thomas A. Russo, Candace M. Marr
Clinical Microbiology Reviews May 2019, 32 (3) e00001-19; DOI: 10.1128/CMR.00001-19

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Hypervirulent Klebsiella pneumoniae
Thomas A. Russo, Candace M. Marr
Clinical Microbiology Reviews May 2019, 32 (3) e00001-19; DOI: 10.1128/CMR.00001-19
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  • Top
  • Article
    • SUMMARY
    • INTRODUCTION
    • HISTORY AND EVOLUTION
    • EPIDEMIOLOGY
    • STRUCTURE AND FUNCTION
    • PATHOGENESIS
    • HOST SUSCEPTIBILITY RISK FACTORS
    • INFECTIOUS SYNDROMES
    • DIAGNOSIS
    • TREATMENT
    • INFECTION CONTROL AND PREVENTION
    • ACKNOWLEDGMENTS
    • REFERENCES
    • Author Bios
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KEYWORDS

Friedlander’s bacillus
Klebsiella pneumoniae
abscess
aerobactin
colonization
hypervirulent
infection control
metastatic spread
virulence determinants
virulence plasmid

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