Journal article
Identification of Biomarkers for Differentiation of Hypervirulent Klebsiella pneumoniae from Classical K. pneumoniae
Journal of clinical microbiology, Vol.56(9), e00776-18
09/2018
DOI: 10.1128/JCM.00776-18
PMCID: PMC6113484
PMID: 29925642
Abstract
A hypervirulent
(hvKp) pathotype is undergoing global dissemination. In contrast to the usual health care-associated epidemiology of classical
(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 (
= 85) and cKp-rich (
= 90) strain cohorts, respectively. The isolates were then assessed for multiple candidate biomarkers hypothesized to accurately differentiate the two cohorts. The genes
,
,
, plasmid-borne
gene (
), and
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.
,
,
,
, and
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.
Details
- Title: Subtitle
- Identification of Biomarkers for Differentiation of Hypervirulent Klebsiella pneumoniae from Classical K. pneumoniae
- Creators
- Thomas A Russo - Veterans Administration Western New York Healthcare System, Buffalo, New York, USARuth Olson - Veterans Administration Western New York Healthcare System, Buffalo, New York, USAChi-Tai Fang - Department of Internal Medicine, National Taiwan University Hospital, Taipei, TaiwanNicole Stoesser - Modernising Medical Microbiology Consortium, University of Oxford, Oxford, United KingdomMark Miller - Department of Medicine, McGill University, Montreal, CanadaUlrike MacDonald - Veterans Administration Western New York Healthcare System, Buffalo, New York, USAAlan Hutson - Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York, USAJason H Barker - Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USARicardo M La Hoz - Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USAJames R Johnson - Minneapolis VA Health Care System and University of Minnesota, Minneapolis, Minnesota, USA
- Resource Type
- Journal article
- Publication Details
- Journal of clinical microbiology, Vol.56(9), e00776-18
- Publisher
- United States
- DOI
- 10.1128/JCM.00776-18
- PMID
- 29925642
- PMCID
- PMC6113484
- ISSN
- 0095-1137
- eISSN
- 1098-660X
- Grant note
- R21 AI123558 / NIAID NIH HHS I01 BX000984 / BLRD VA
- Language
- English
- Date published
- 09/2018
- Academic Unit
- Infectious Diseases; Internal Medicine
- Record Identifier
- 9984071800302771
Metrics
23 Record Views