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Olorofim activity against multidrug-resistant Fusarium unveils intra-species and inter-species variability

Summary

Researchers tested a new antifungal drug called olorofim against 253 different Fusarium fungi that infect humans. Fusarium is particularly dangerous for people with weakened immune systems and resists most common antifungals. The study found that olorofim works, but its effectiveness varies significantly depending on which type of Fusarium is present. While these lab results are promising, additional testing in animal models is needed before it can be used clinically.

Background

Fusarium species are environmental fungi that cause serious infections in immunocompromised patients and are notoriously resistant to standard antifungal drugs. Olorofim is a novel orotomide-class antifungal that inhibits dihydroorotate dehydrogenase and interferes with pyrimidine biosynthesis. Previous studies have reported variable in vitro activity of olorofim against Fusarium species.

Objective

To evaluate the in vitro susceptibility of 253 well-characterized Fusarium isolates to olorofim and assess intra-species and inter-species variability. The study aimed to provide evidence for potential clinical application of olorofim against multidrug-resistant Fusarium infections.

Results

The geometric mean MIC of olorofim for all isolates was 0.581 µg/mL, ranging from 0.015 to >16 µg/mL. F. solani species complex showed significantly higher MICs (GM 1.602 µg/mL) compared to F. fujikuroi species complex (GM 0.137 µg/mL). Clinical isolates had higher MIC values than environmental isolates, though this pattern was not consistent across all species complexes.

Conclusion

Olorofim demonstrates moderate and variable in vitro activity against Fusarium isolates, with significant inter-species and intra-species variability. While olorofim may be a potential candidate for treating multidrug-resistant fusarioses, low MIC values do not necessarily predict clinical efficacy, and further animal model studies are required to establish clinical utility.
  • Published in:Antimicrobial Agents and Chemotherapy,
  • Study Type:In Vitro Susceptibility Study,
  • Source: 10.1128/aac.00961-25; PMID: 41071100
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