Olorofim activity against multidrug-resistant unveils intra-species and inter-species variability.
Series / Report no.
Open Access
Type
Journal Article
Article
Article
Language
en
Date
2025-10-10
Research Projects
Organizational Units
Journal Issue
Title
Olorofim activity against multidrug-resistant unveils intra-species and inter-species variability.
Translated Title
Published in
Antimicrob Agents Chemother 2025; 69(11):e0096125
Abstract
Fungi in the genus are plant pathogens but are also capable of causing a wide range of diseases in humans. The intrinsic multi-drug resistance of often leads to a poor clinical outcome in patients with severe immune disorders. Olorofim, a member of the orotomide class, is a novel type of antifungal drug that interferes with pyrimidine biosynthesis by inhibiting dihydroorotate dehydrogenase and thereby prevents growth and cell division. In this study, the activity of olorofim was evaluated against 253 isolates, of which 228 isolates belonging to the prevalent complexes involved in human infection, species complex (SC) and SC. All isolates underwent species-level identification via multi-locus sequence typing (MLST) targeting , , and loci. Antifungal susceptibility testing was performed using a CLSI M38, 3rd ed. broth microdilution for olorofim. The geometric mean of the MICs of olorofim for all 253 isolates was 0.581 µg/mL, ranging from 0.015 µg/mL to >16 µg/mL. Olorofim demonstrated high MICs against SC, whereas greater potency (lower MICs) was observed against SC. Clinical isolates tended to have higher MIC values than environmental isolates, but this pattern was not consistent across all species complexes. Overall, olorofim demonstrated moderate activity against isolates, suggesting it might be a potential candidate for treating fusarioses caused by multidrug-resistant strains.