EUCAST-Obtained Olorofim MICs against Aspergillus and Scedosporium Species and Lomentospora prolificans Showed High Agreements between Visual Inspection and Spectrophotometric Readings

Antimicrob Agents Chemother. 2022 Sep 20;66(9):e0084922. doi: 10.1128/aac.00849-22. Epub 2022 Aug 4.

Abstract

Previous studies show high agreement between MIC spectrophotometric readings and visual inspection of azoles and amphotericin B against Aspergillus fumigatus isolates. Here, we tested and compared the in vitro activity of a novel antifungal, olorofim, against Aspergillus spp., Scedosporium spp., and Lomentospora prolificans by visual inspection and spectrophotometric readings. Clinical isolates of Aspergillus (n = 686) and Scedosporium (n = 36) spp. and L. prolificans (n = 13) were tested. Olorofim MICs were evaluated-following the EUCAST E.Def 9.4 procedure-by visual inspection or spectrophotometric readings (combinations of either ≥90% or ≥95% fungal growth inhibition endpoints compared to drug-free control endpoints and different wavelengths [405 nm, 450 nm, 492 nm, 540 nm, and 620 nm]). We observed high in vitro activity of olorofim against all tested Aspergillus spp. (MICs up to 0.06 mg/L), except for A. calidoustus, and against L. prolificans and Scedosporium spp. (MICs up to 0.125 mg/L). The combination of ≥90% fungal growth inhibition endpoints at wavelengths of ≥492 nm resulted in high essential agreements with A. fumigatus and lesser agreement with non-fumigatus Aspergillus, Scedosporium spp., and L. prolificans, although the number of isolates studied was low. This single-center study shows high agreement among olorofim MICs against A. fumigatus by visual inspection and spectrophotometric readings (≥90% fungal growth inhibition endpoints and wavelengths of ≥492 nm) and encouraging results against non-fumigatus Aspergillus spp., Scedosporium spp., and L. prolificans.

Keywords: Aspergillus; EUCAST; Lomentospora prolificans; Scedosporium; olorofim; spectrophotometric reading.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides
  • Amphotericin B / pharmacology
  • Antifungal Agents / pharmacology
  • Antifungal Agents / therapeutic use
  • Aspergillus
  • Piperazines
  • Pyrimidines
  • Pyrroles / pharmacology
  • Scedosporium*

Substances

  • Acetamides
  • Antifungal Agents
  • Piperazines
  • Pyrimidines
  • Pyrroles
  • Amphotericin B
  • olorofim