Antifungal susceptibility profiles of clinical and environmental Scedosporium and Lomentospora isolates from Taiwan: focus on olorofim activity and phylogenetic heterogeneity

BACKGROUND: Scedosporium and Lomentospora species are intrinsically resistant moulds increasingly implicated in invasive infections. Olorofim, a novel orotomide antifungal, has demonstrated potent activity against several moulds. This study evaluated the antifungal susceptibility of clinical and environmental isolates, focusing on olorofim, and examined these data in a phylogenetic context. METHODS: A total of 216 isolates (Scedosporium spp., n = 205; L. prolificans, n = 11) were collected from clinical and environmental sources across Taiwan. Antifungal susceptibility was determined using the CLSI M38-A3 method. Correlation analyses assessed cross-resistance patterns, while phylogenetic signal, Mantel tests, and variance partitioning were used to evaluate evolutionary structuring of MICs. RESULTS: Scedosporium apiospermum (46.3%) and S. boydii (15.7%) were the predominant species, exhibiting comparable triazole susceptibility profiles (MIC90: voriconazole 1-2 mg/L, posaconazole 4 mg/L, and isavuconazole 8 mg/L). L. prolificans displayed pan-resistance to all agents except olorofim. Olorofim exhibited the lowest MICs across Scedosporium spp. and L. prolificans (all MIC90 ≤ 0.12 mg/L). The isolate source exerted limited biological impact on antifungal susceptibility campared with species-specific characteristics. The association between antifungal susceptibility and species relatedness varied by drug: moderate for posaconazole, amphotericin B, and voriconazole; intermediate for olorofim; weak for isavuconazole; and absent for itraconazole. The majority of MIC variability (72.5%-89.2%) was observed within rather than between species. CONCLUSIONS: Susceptibility in Scedosporium and Lomentospora exhibits high intraspecies variability. Triazoles showed only moderate phylogenetic conservation and cross-resistance, whereas olorofim demonstrated potent, independent activity across all taxa. Given the limited predictive value of species identity, individual susceptibility testing remains essential.