Identification of biomarkers for the differentiation of hypervirulent Klebsiella pneumoniae from classical K. pneumoniae

Background. A hypervirulent Klebsiella pneumoniae (hvKp) pathotype is undergoing global dissemination. In contrast to the usual healthcare-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. Methods and Results. 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 strain (N = 85) and cKp-rich (N = 90) cohorts respectively. The isolates were then assessed for multiple candidate biomarkers hypothesized to accurately differentiate the two cohorts. The genes peg-344 , iroB, iucA , p rmpA , and p rmpA2 all demonstrated u003e0.95 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 , p rmpA , and p rmpA2 were all associated with a hazard ratio of u003e25 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. Lastly, using the most accurate biomarkers to define hvKp, prevalence studies were performed on two Western strain collections. Conclusions. These data strongly support the utility of several laboratory markers for identifying hvKp strains with a high degree of accuracy.