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Olorofim demonstrates in vitro activity against Coccidioides species, including isolates against which fluconazole

Nathan P Wiederhold1,2, Hoja P Patterson1, Dora Ferrer1

  • 1Fungus Testing Laboratory, Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.

Antimicrobial Agents and Chemotherapy
|November 21, 2024
PubMed

Insights

Olorofim shows strong in vitro antifungal activity against Coccidioides species. This potent activity was effective even against fungal isolates resistant to fluconazole.

Area of Science:

  • Mycology
  • Antifungal Research
  • Infectious Diseases

Background:

  • Coccidioides species are pathogenic fungi causing coccidioidomycosis.
  • Antifungal resistance is a growing concern in treating fungal infections.
  • Limited treatment options exist for severe or refractory coccidioidomycosis.

Purpose of the Study:

  • To evaluate the in vitro antifungal activity of olorofim against various Coccidioides species.
  • To determine the minimum inhibitory concentrations (MICs) of olorofim.
  • To assess olorofim's efficacy against fluconazole-resistant Coccidioides isolates.

Main Methods:

  • In vitro susceptibility testing was performed on Coccidioides isolates.
  • Minimum Inhibitory Concentrations (MICs) were determined for olorofim.
  • Isolates with known elevated fluconazole MICs were specifically included.

Main Results:

  • Olorofim exhibited potent in vitro activity against all tested Coccidioides isolates.
  • The geometric mean MIC for olorofim was as low as 0.010 µg/mL.
  • Olorofim maintained potent activity against isolates with high-level fluconazole resistance (MICs ≥16 µg/mL and ≥32 µg/mL).

Conclusions:

  • Olorofim demonstrates significant in vitro potency against Coccidioides species.
  • Olorofim is a promising candidate for treating coccidioidomycosis, including fluconazole-resistant cases.
  • Further clinical investigation of olorofim for coccidioidomycosis is warranted.
Keywords:
Coccidioides speciesfluconazolein vitro susceptibilityolorofim

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