Elexacaftor/Tezacaftor/Ivacaftor (Trikafta®) does not affect the Growth ofAspergillus fumigatus in vitro

Abstract

AbstractFungal infection, especially allergic bronchopulmonary aspergillosis, is a leading cause of infection-associated morbidity and death in patients with cystic fibrosis. We have previously discovered that the new leading therapeutic treatment in cystic fibrosis, CFTR modulators Elexakaftor/Tezacaftor/Ivacaftor (ETI, Trikafta®), drastically reduces the colonization and infection byAspergillus fumigatus. However, the reasons for this decrease in patients are not known so far. In this study we have shown, usingA. fumigatusreference strains and strains isolated from patients with cystic fibrosis, that CFTR modulators have no discernable impact on fungal growthin vitro. These results are consistent regardless of drugs concentration, demonstrating that treatment does not exert a direct antimicrobial or stimulatory effectin vitroonA. fumigatusconidia growth, when exposed to actualin vivoCFTR modulators concentration.