Epidemiology of Tardiomyces blankii (formerly Candida blankii ) and related species: results of the International “Epiblankii” Study

ABSTRACT Tardiomyces blankii (previously known as Candida blankii ) is an understudied emerging fungal pathogen with an unusual susceptibility profile. The aim of this study was to improve our understanding of the epidemiology of Tardiomyces spp. Cases were collected through two surveillance networks. The first was the Mass Spectrometry Identification (MSI) international network (La Pitié-Salpêtrière Hospital, Paris, France), based on mass spectrometry to identify fungal pathogens. The second was Canisius-Wilhelmina Hospital, Center of Expertise for Mycology (Nijmegen, the Netherlands). MSI members who had identified at least one T. blankii isolate between 2019 and 2025 collected retrospective data and provided their isolates. In vitro antifungal susceptibility testing (AFST) was carried out for 10 antifungal drugs. Whole-genome sequencing single-nucleotide polymorphism analysis was conducted to assess genetic diversity. Over the period 2019–2025, 251 spectra submitted to the MSI application were identified as T. blankii sensu lato . From the two surveillance networks, 46 isolates were available for further analysis, leading to the identification of 34 T. blankii , 11 Tardiomyces depauwii , and 1 Tardiomyces digboiensis . Clinical isolates were related to 29 cases of infection/colonization. The AFST data showed high minimum inhibitory concentration (MIC) values for azoles and echinocandins. Interestingly, these isolates demonstrated elevated MICs for anidulafungin and caspofungin but not micafungin. A low genetic diversity was found in T. depauwii isolates, while T. blankii isolates showed considerable genetic variation, although most French isolates formed a distinct clade. Our study sheds light on these rare human-pathogenic yeast species that exhibit reduced susceptibility to antifungal drugs. IMPORTANCE Tardiomyces spp. (formerly classified as Candida blankii ) are emerging opportunistic yeasts that remain poorly recognized in routine clinical microbiology. To improve our understanding of the epidemiology of Tardiomyces spp., we combined data from the Mass Spectrometry Identification international network (Paris, France) and the Center of Expertise for Mycology (Nijmegen, the Netherlands) with whole-genome sequencing and antifungal susceptibility testing. We show that improving MALDI-TOF MS databases markedly enhances species identification, allowing discrimination between Tardiomyces blankii , Tardiomyces depauwii , and Tardiomyces digboiensis . Our findings also identify at-risk patients, describe the antifungal susceptibility profiles of these emerging pathogens, and reveal distinct patterns of genetic diversity. As uncommon fungal pathogens are increasingly encountered in vulnerable patients, accurate laboratory identification is essential for surveillance, epidemiology, and clinical management. These results provide practical tools and new knowledge that will facilitate the recognition and monitoring of this neglected genus.