Nathan P Wiederhold1, Derek Law2, Michael Birch2. 1. Fungus Testing Laboratory, Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. 2. F2G Limited, Manchester, UK.
Abstract
Background: Scedosporium species and Lomentospora prolificans are increasing causes of invasive infections in immunocompromised hosts and many isolates are resistant to available antifungals. Our objective was to assess the in vitro potency of F901318, a member of the orotomide class of antifungals, against Scedosporium species and L. prolificans . Methods: The in vitro potency of F901318 was evaluated against 66 Scedosporium and 7 L. prolificans clinical isolates using the CLSI M38-A2 reference standard. Scedosporium species included Scedosporium apiospermum ( n = 43), Scedosporium aurantiacum ( n = 6), Scedosporium dehoogii ( n = 2) and Scedosporium boydii ( n = 15). Positive comparators included amphotericin B, caspofungin, posaconazole and voriconazole. Results: Against S. apiospermum and S. boydii F901318 geometric mean MICs/MECs (0.079 and 0.046 mg/L, respectively) were significantly lower than those observed with amphotericin (3.404 and 5.595 mg/L), posaconazole (1.937 and 1.823 mg/L), voriconazole (0.784 and 0.630 mg/L) and caspofungin (5.703 and 7.639 mg/L) ( P < 0.001). Against S. aurantiacum and S. dehoogii the F901318 MIC range (0.12-0.5 mg/L) was also lower than those for the other antifungals (0.5 to >8 mg/L). F901318 also maintained activity against L. prolificans isolates (range 0.12-0.25 mg/L) in contrast to other antifungals, of which none demonstrated in vitro activity. Conclusions: F901318 demonstrated potent in vitro activity against Scedosporium species and L. prolificans . This activity was maintained against isolates that had significantly reduced susceptibility to the other antifungals. Further studies are warranted to evaluate the in vivo efficacy of F901318 against Scedosporium species and L. prolificans .
Background: Scedosporium species and Lomentospora prolificans are increasing causes of invasive infections in immunocompromised hosts and many isolates are resistant to available antifungals. Our objective was to assess the in vitro potency of F901318, a member of the orotomide class of antifungals, against Scedosporium species and L. prolificans . Methods: The in vitro potency of F901318 was evaluated against 66 Scedosporium and 7 L. prolificans clinical isolates using the CLSI M38-A2 reference standard. Scedosporium species included Scedosporium apiospermum ( n = 43), Scedosporium aurantiacum ( n = 6), Scedosporium dehoogii ( n = 2) and Scedosporium boydii ( n = 15). Positive comparators included amphotericin B, caspofungin, posaconazole and voriconazole. Results: Against S. apiospermum and S. boydiiF901318 geometric mean MICs/MECs (0.079 and 0.046 mg/L, respectively) were significantly lower than those observed with amphotericin (3.404 and 5.595 mg/L), posaconazole (1.937 and 1.823 mg/L), voriconazole (0.784 and 0.630 mg/L) and caspofungin (5.703 and 7.639 mg/L) ( P < 0.001). Against S. aurantiacum and S. dehoogii the F901318 MIC range (0.12-0.5 mg/L) was also lower than those for the other antifungals (0.5 to >8 mg/L). F901318 also maintained activity against L. prolificans isolates (range 0.12-0.25 mg/L) in contrast to other antifungals, of which none demonstrated in vitro activity. Conclusions: F901318 demonstrated potent in vitro activity against Scedosporium species and L. prolificans . This activity was maintained against isolates that had significantly reduced susceptibility to the other antifungals. Further studies are warranted to evaluate the in vivo efficacy of F901318 against Scedosporium species and L. prolificans .
Authors: Nathan P Wiederhold; Laura K Najvar; Rosie Jaramillo; Marcos Olivo; Michael Birch; Derek Law; John H Rex; Gabriel Catano; Thomas F Patterson Journal: Antimicrob Agents Chemother Date: 2018-08-27 Impact factor: 5.191
Authors: Carsten Müller; Cornelia Fietz; Philipp Koehler; Graham Sibley; Achu Che Awah Nforbugwe; Thomas Streichert; Martin H J Wiesen Journal: Antimicrob Agents Chemother Date: 2018-10-24 Impact factor: 5.191
Authors: S Seyedmousavi; Y C Chang; J H Youn; D Law; M Birch; J H Rex; K J Kwon-Chung Journal: Antimicrob Agents Chemother Date: 2021-07-12 Impact factor: 5.191