Antimicrobial activity of manogepix, a first-in-class antifungal, and comparator agents tested against contemporary invasive fungal isolates from an international surveillance programme (2018-2019).
J Glob Antimicrob Resist
; 26: 117-127, 2021 09.
Article
em En
| MEDLINE
| ID: mdl-34051400
ABSTRACT
OBJECTIVES:
Manogepix, the active moiety of the prodrug fosmanogepix, is a novel antifungal with activity against major fungal pathogens including Candida (except Candida krusei), Aspergillus and difficult-to-treat/rare moulds. We tested manogepix and comparators against 2669 contemporary (2018-2019) fungal isolates collected from 82 medical centres 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 for antifungal susceptibility by the CLSI reference broth microdilution method.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) had comparable activity to anidulafungin and micafungin. Low manogepix concentrations inhibited uncommon species of Candida, non-Candida yeasts, and rare moulds including Scedosporium spp. and Lomentospora (Scedosporium) prolificans.CONCLUSION:
Manogepix exhibited potent activity against contemporary fungal isolates, including echinocandin- and azole-resistant strains of Candida and Aspergillus spp., respectively. Although rare, Candida strains 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 are underway to evaluate the utility of fosmanogepix against difficult-to-treat resistant fungal infections.Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Isoxazóis
/
Antifúngicos
Tipo de estudo:
Screening_studies
Idioma:
En
Revista:
J Glob Antimicrob Resist
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos