Phenotypic and genotypic differences between bloodstream and non-blood <i>Candida krusei</i> isolates: implications for invasiveness and antifungal susceptibility

<i>Candida krusei</i> is an opportunistic pathogen with intrinsic resistance to fluconazole. This study analyzed 174 <i>C</i>. <i>krusei</i> isolates from bloodstream infections (BSI, <i>n</i> = 115) and non-blood sources (<i>n</i> = 59). Biochemical profiling using the VITEK 2 YST ID Card revealed a significant difference in the TyrA reaction between BSI and non-blood isolates (<i>P</i> < 0.05). Antifungal susceptibility testing via CLSI broth microdilution and Sensititre YeastOne showed that BSI isolates were more susceptible to echinocandins and azoles than non-blood strains, with minor MIC discrepancies between methods. Microsatellite genotyping at eight loci demonstrated high genetic diversity. Notably, a cluster of respiratory isolates from COVID-19 patients suggested potential nosocomial transmission. The integration of phenotypic, susceptibility, and genotypic data highlights possible virulence traits and epidemiological patterns. These findings may support the development of tailored antifungal therapies and improved infection control, particularly for high-risk populations such as ICU and COVID-19 patients.IMPORTANCEBloodstream infections caused by <i>C. krusei</i> are associated with high mortality rates and limited therapeutic options, emphasizing the need to better understand the factors contributing to its pathogenicity and invasive potential. This study provides critical insights into the biology and clinical impact of <i>C. krusei</i>. By integrating biochemical, antifungal susceptibility, and genotypic analyses of bloodstream and non-bloodstream isolates, it reveals distinct phenotypic and resistance profiles, high genetic diversity, and potential nosocomial transmission in COVID-19 patients. These findings underscore the importance of recognizing population-specific traits in <i>C. krusei</i>, which may guide tailored antifungal strategies and strengthen infection control measures, especially for vulnerable groups such as ICU and immunocompromised patients.