
doi: 10.2139/ssrn.6981770
Background: Klebsiella pneumoniae is a major cause of community- and healthcare-associated infections worldwide. While classical K. pneumoniae (cKp) is recognized for multidrug resistance, hypervirulent K. pneumoniae (hvKp) carries enhanced virulence traits that enable tissue-invasive disease. Testing for hvKp is not routinely performed in clinical laboratories outside Asia, raising the possibility that strains with invasive potential circulate undetected. The prevalence and invasive potential of hvKp in U.S. healthcare settings remain poorly defined. <div> <br> </div> <div> Methods: We screened 549 clinical K. pneumoniae isolates from two academic healthcare systems in North Carolina for hypermucoviscosity (HMV), a phenotypic proxy for hvKp, using a quantitative sedimentation resistance assay. HMV-positive isolates were characterized using human serum survival assays and whole-genome sequencing to identify virulence-associated genetic determinants. A subset was evaluated in a disseminating wound infection model in immunocompetent mice. Selected isolates were further tested in a diabetic mouse model to examine the impact of host metabolic status on virulence. </div> <div> <br> </div> <div> Findings: Overall, 17 of the 549 (3·1%) K. pneumoniae isolates were HMV-positive. HMV prevalence was similar in community- versus healthcare-associated isolates (4% v. 2·1%, p=0·21), and between blood and non-blood sources (3·2% v. 3·0%, p=1·00). In an immunocompetent murine disseminating wound infection model, only a subset of HMV-positive isolates caused invasive infection. However, five HMV-positive isolates that were avirulent in immunocompetent mice became invasive in diabetic mice, demonstrating that diabetic host status can unmask invasive potential. </div> <div> <br> </div> <div> Interpretation: HMV-positive K. pneumoniae circulate unrecognized within U.S. healthcare systems. Although HMV alone does not predict invasive disease in immunocompetent hosts, diabetic host status can unmask the invasive potential of HMV-positive isolates that otherwise appear avirulent. These findings suggest that healthy animal models may underestimate the pathogenic potential of isolates recovered from patients with diabetes and support routine HMV surveillance in clinical microbiology. </div>
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