In vitro activity of ibrexafungerp against Candida species isolated from blood cultures. Determination of wild type populations using the EUCAST method.

Abstract Objectives Ibrexafungerp is a new oral glucan synthase inhibitor with in vivo and in vitro activity against Candida spp, including echinocandin- and azole-resistant isolates. We studied the in vitro activity of ibrexafungerp against Candida species isolated from blood cultures and assessed wild type upper limits against the five Candida species most frequently associated to candidaemia. Methods Isolates (n=958) causing incident episodes of candidaemia in patients admitted to Gregorio Maranon hospital (Madrid, Spain) between January 2007 and April 2021 were studied. Antifungal susceptibility to ibrexafungerp, fluconazole, micafungin, and anidulafungin was tested (EUCAST 7.3.2) and wild type upper limits determined against C. albicans (n=462), C. glabrata (n=120), C. parapsilosis (n=249), C. tropicalis (n=73), and C. krusei (n=24). FKS gene sequencing was carried out in non-wild type isolates. Results Ibrexafungerp showed antifungal in vitro activity against the studied isolates. Wild type upper limits for ibrexafungerp were > 0.25 mg/L against C. albicans, > 1 mg/L against C. parapsilosis, C. glabrata, and C. tropicalis, and > 2 mg/L against C. krusei. Percentages of ibrexafungerp non-wild type isolates were low (C. parapsilosis and C. krusei, 0%; C. albicans, 0.22% [1/462]; C. glabrata, 0.83% [1/120]; and C. tropicalis, 1.37% [1/73]). Ibrexafungerp proved in vitro activity against fluconazole- or echinocandin-resistant isolates. Conclusions We show in vitro activity of ibrexafungerp against the tested Candida species. Furthermore, we provide ibrexafungerp wild type upper limits, which allows defining the wild type populations of the five most relevant Candida species.