AbstractTwo types of Klebsiella pneumoniae (KP) strains are currently emerging: hypervirulent (hvKP) strains and carbapenem-resistant (CR-KP) strains. To date, these two strain types rarely overlap. Recent reports, however, suggest that CR-KP strains are increasing in virulence. hvKP strains frequently present as highly invasive infections, such as necrotizing skin and soft tissue infections (NSSTI). To examine whether CR-KP strains with features of hvKP were present in our U.S. hospital, we retrospectively identified four cases of CR-KP NSSTI diagnosed between January 2012 and January 2016. Whole-genome sequencing was used to perform multilocus sequence typing, capsular typing, and identification of virulence and antimicrobial resistance genes. Additionally, the virulence of each isolate was determined in vitro and using murine pneumonia and subcutaneous infection models. We identified one CR-KP isolate that possessed features of hypervirulent KP, including a hypermucoviscous phenotype, K2 capsule, and resistance to phagocytosis. Of the four CR-KP isolates, two had no evidence of enhanced pathogenicity in either mouse model, demonstrating that low-virulence strains can cause NSSTI in immunosuppressed patients. The remaining two isolates exhibited low virulence in the pneumonia model but high virulence in the subcutaneous infection model, suggesting that the virulence attributes of these isolates are adapted to causing NSSTI.