In vitro activity of manogepix and comparators against infrequently encountered yeast and mold isolates from the SENTRY Surveillance Program (2017-2022).

Manogepix is a potent new antifungal agent targeting the fungal Gwt1 enzyme. Manogepix has previously demonstrated potent in vitro activity against clinical isolates of both Candida (except Candida krusei ) and Aspergillus species. This study determined the in vitro activity of manogepix and comparators against a large collection of infrequently encountered yeast and molds. Manogepix demonstrated potent in vitro activity against infrequently encountered yeasts exhibiting elevated MIC values to other drug classes, including Candida spp. (MIC 50/90 , 0.008/0.12 mg/L), Saprochaete clavata ( Magnusiomyces clavatus ) (MIC 50/90 , 0.03/0.06 mg/L), Magnusiomyces capitatus (MIC range , 0.016-0.06 mg/L), Rhodotorula minuta (MIC, 0.016 mg/L), and Rhodotorula mucilaginosa (MIC 50/90 , 0.03/0.12 mg/L). Similarly, manogepix was active against infrequently encountered mold isolates and strains exhibiting elevated MIC/MEC values to echinocandins, azoles, and amphotericin B, including Coprinopsis cinerea (MEC, 0.004 mg/L), Fusarium spp. (MEC 50/90 , 0.016/0.06 mg/L), Fusarium ( Gibberella ) fujikuroi species complex (MEC 50/90 , 0.016/0.03 mg/L), Lomentospora prolificans (MEC 50/90 , 0.03/0.06 mg/L), Microascus cirrosus (MEC, 0.008 mg/L), Paecilomyces spp. (MEC 50/90 , ≤0.008/0.016 mg/L), Pleurostomophora richardsiae (MEC, 0.06 mg/L), Sarocladium kiliense (MEC range, 0.016-0.12 mg/L), and Scedosporium spp. (MEC 50/90 , 0.03/0.06 mg/L). Manogepix demonstrated potent activity against a majority of the infrequently encountered yeast and mold isolates tested including strains with elevated MIC/MEC values to other drug classes. Additional clinical development of manogepix (fosmanogepix) in difficult-to-treat, resistant fungal infections is warranted.