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J Clin Microbiol. 2018 Aug 27;56(9). pii: e00776-18. doi: 10.1128/JCM.00776-18. Print 2018 Sep.

Identification of Biomarkers for Differentiation of Hypervirulent Klebsiella pneumoniae from Classical K. pneumoniae.

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Department of Medicine, University at Buffalo, State University of New York, Buffalo, New York, USA
Department of Microbiology and Immunology, The Witebsky Center for Microbial Pathogenesis, University at Buffalo, State University of New York, Buffalo, New York, USA.
Veterans Administration Western New York Healthcare System, Buffalo, New York, USA.
Department of Medicine, University at Buffalo, State University of New York, Buffalo, New York, USA.
Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan.
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Modernising Medical Microbiology Consortium, University of Oxford, Oxford, United Kingdom.
Department of Medicine, McGill University, Montreal, Canada.
Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York, USA.
Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA.
Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Minneapolis VA Health Care System and University of Minnesota, Minneapolis, Minnesota, USA.


A hypervirulent Klebsiella pneumoniae (hvKp) pathotype is undergoing global dissemination. In contrast to the usual health care-associated epidemiology of classical K. pneumoniae (cKp) infections, hvKp causes tissue-invasive infections in otherwise healthy individuals from the community, often involving multiple sites. An accurate test to identify hvKp strains is needed for improved patient care and epidemiologic studies. To fill this knowledge gap, clinical criteria or random blood isolates from North American and United Kingdom strain collections were used to assemble hvKp-rich (n = 85) and cKp-rich (n = 90) strain cohorts, respectively. The isolates were then assessed for multiple candidate biomarkers hypothesized to accurately differentiate the two cohorts. The genes peg-344, iroB, iucA, plasmid-borne rmpA gene ( prmpA), and prmpA2 all demonstrated >0.95 diagnostic accuracy for identifying strains in the hvKp-rich cohort. Next, to validate this epidemiological analysis, all strains were assessed experimentally in a murine sepsis model. peg-344, iroB, iucA, prmpA, and prmpA2 were all associated with a hazard ratio of >25 for severe illness or death, additionally supporting their utility for identifying hvKp strains. Quantitative siderophore production of ≥30 μg/ml also strongly predicted strains as members of the hvKp-rich cohort (accuracy, 0.96) and exhibited a hazard ratio of 31.7 for severe illness or death. The string test, a widely used marker for hvKp strains, performed less well, achieving an accuracy of only 0.90. Last, using the most accurate biomarkers to define hvKp, prevalence studies were performed on two Western strain collections. These data strongly support the utility of several laboratory markers for identifying hvKp strains with a high degree of accuracy.


biomarkers; classical Klebsiella pneumoniae; diagnosis; diagnostic test; hypervirulent Klebsiella pneumoniae

[Available on 2019-02-27]

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