M. Pfaller, M. Huband, R. Flamm
May 26, 2021
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0
Influential Citations
17
Citations
Quality indicators
Journal
Journal of global antimicrobial resistance
Abstract
OBJECTIVES Manogepix, the active moiety of the prodrug fosmanogepix, is a novel antifungal with activity against major fungal pathogens including Candida (except C. krusei), Aspergillus, and difficult-to-treat/rare moulds. We tested manogepix and comparators against 2,669 contemporary (2018-2019) fungal isolates collected from 82 medical centers located in North America (42.3%), Europe (37.9%), Asia-Pacific (12.3%), and Latin America (7.6%). Of these, 70.7% were Candida spp.; 3.6% were non-Candida yeasts, including 49 Cryptococcus neoformans var. grubii; 21.7% were Aspergillus spp.; and 4.1% were other moulds. METHODS Isolates were tested by CLSI reference broth microdilution. RESULTS Manogepix (MIC50/90, 0.008/0.06 mg/L) was the most active agent tested against Candida spp. isolates; corresponding anidulafungin, micafungin, and fluconazole MIC90 values were 16- to 64-fold higher. Similarly, manogepix (MIC50/90, 0.5/2 mg/L) was ≥4-fold more active than anidulafungin, micafungin, and fluconazole against C. neoformans var. grubii. Against Aspergillus spp., manogepix (MEC50/90, 0.015/0.03 mg/L) was comparable in activity to anidulafungin and micafungin. Low manogepix concentrations inhibited uncommon species of Candida, non-Candida yeasts, and rare moulds, including Scedosporium spp. and Lomentospora prolificans. CONCLUSIONS Manogepix exhibited potent activity against contemporary fungal isolates, including echinocandin- and azole-resistant strains of Candida and Aspergillus spp., respectively. Although rare, strains of Candida that were non-wild type for manogepix demonstrated resistance to fluconazole. However, the clinical relevance of this finding is unknown. The extended spectrum of manogepix is noteworthy for its activity against many less common, yet antifungal-resistant strains. Clinical studies underway to evaluate the utility of fosmanogepix against difficult-to-treat resistant fungal infections.