Clinical significance and antifungal susceptibility profile of 103 clinical isolates of <i>Scedosporium</i> species complex and <i>Lomentospora prolificans</i> obtained from NIH patients

Reduced susceptibility to antifungals is common among members of genera <i>Scedosporium</i> and <i>Lomentospora</i>, with optimal treatments still not fully defined. <i>In vitro</i> antifungal susceptibility results and clinical data do not comprehensively account for the advent of new <i>Scedosporium</i> species identified by molecular phylogenetics. Using Clinical and Laboratory Standards Institute (CLSI) methodology, we tested a total of 103 clinical isolates obtained from patients at the NIH Clinical Center. The most frequent species were <i>Scedosporium apiospermum</i> (63%) and <i>Scedosporium boydii</i> (11%), followed by <i>Lomentospora prolificans</i> (7%). The novel antifungal olorofim showed the lowest MICs against all <i>Scedosporium</i> spp. and <i>L. prolificans</i>, followed by micafungin. Among the triazoles, voriconazole showed lower MICs against <i>Scedosporium</i> spp. Amphotericin B and posaconazole demonstrated species-specific and inter-species variable activity. Itraconazole, isavuconazole, and terbinafine had higher MIC values against <i>Scedosporium</i> spp. and <i>L. prolificans</i>. Clinical data were retrospectively reviewed for 90 isolates, of which nine patients (28 isolates) had active disease/infection and received antifungal treatment that included voriconazole or posaconazole. Five of these patients (56%) died, while three patients (33%) with chronic granulomatous disease were cured following hematopoietic cell transplantation. In 24 patients (62 isolates), the presence of the fungus was considered airway colonization. In conclusion, our data support the existence of species-specific and inter-species differences in the antifungal susceptibility patterns among members of genera <i>Scedosporium</i> and <i>L. prolificans</i>. The novel investigational antifungal olorofim may be a promising therapy. Our clinical data suggest that host status and administration of antifungal therapy most effective for each <i>Scedosporium</i> species complex are important determinants of outcomes.IMPORTANCEUnderstanding the epidemiology and clinical spectrum of infections caused by <i>Scedosporium</i> species complex and <i>Lomentospora prolificans</i> is integral to improving outcomes, particularly in severely ill and immunocompromised patients. <i>In vitro</i> antifungal susceptibility testing can provide an estimate of antifungal activity against fungal pathogens. Our study showed that species-specific and inter-species differences exist in the distribution of antifungal susceptibility patterns between <i>Scedosporium</i> and <i>L. prolificans</i>. Our clinical data also highlight that host status, along with effective antifungal therapy, plays a crucial role in determining treatment outcomes.