Activity of F901318 against azole-resistant and other difficult-to-treat Aspergillus species

J Buil


Background: F90138 is a new antifungal agent with a novel mechanism of action and in vitro activityagainst Aspergillus (Asp) species. We investigated the in vitro activity of F901318 against a   collection of difficult-to-treatAsp. isolates.

Material/methods: The in vitro activity of F901318 was tested against 213 Asp. isolates including 133 azole-resistant A. fumigatus (25 TR34/L98H; 25 TR46/Y121F/T289A; 33A. fumigatuswith point mutations; and 50 azole-resistant A. fumigatus without known resistance mechanism) and 10 wild type controls. The in vitro activity was also determined against A. calidoustus (25 isolates), A. flavus (10),A. nidulans (10) and A. tubingensus (25). The in vitro activity was compared with itraconazole,voriconazole, posaconazole, isavuconazole, amphotericin B, and anidulafungin. MICs were determined in duplicate using the EUCAST broth microdilution method. The mean of the two replicates was used for analysis.

Results: F901318 wasactive against all tested isolates:A. fumigatus WT: MIC900.125 mg/l (range: 0.031 – 0.125); TR34/L98H,TR46/Y121F/T289A and azole resistant with unknown resistancemechanism: MIC90 0.125 mg/l (0.031-0.25); azole-resistant with point mutations: MIC90 0.062 mg/l (0.015-0.125). Other species:A. calidoustus MIC90 0.5 mg/l (0.125-0.5); A. flavus MIC900.062 mg/l (0.015 – 0.62); A. nidulans MIC90 0.125 mg/l (0.062-0.25), and A. tubingensisMIC90 0.062 mg/l (0.015-0.25)(Table).

Conclusions: F901318 showed excellent and consistent in vitro activity against Asp species with intrinsic azole resistance and acquired resistance due to various known and unknown resistance mechanisms, suggesting no significant implications of azole resistance mechanisms on the mode of action of F901318.




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European Congress of Clinical Microbiology and Infectious Diseases
    • ECCMID 26th (2016)