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)
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 contempora...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-09-01
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| Series: | Journal of Global Antimicrobial Resistance |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213716521001119 |
| _version_ | 1819112767931547648 |
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| author | Michael A. Pfaller Michael D. Huband Robert K. Flamm Paul A. Bien Mariana Castanheira |
| author_facet | Michael A. Pfaller Michael D. Huband Robert K. Flamm Paul A. Bien Mariana Castanheira |
| author_sort | Michael A. Pfaller |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T04:18:45Z |
| format | Article |
| id | doaj.art-efc20a7303c74cdcbe326752c5355ae6 |
| institution | Directory Open Access Journal |
| issn | 2213-7165 |
| language | English |
| last_indexed | 2024-12-22T04:18:45Z |
| publishDate | 2021-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Global Antimicrobial Resistance |
| spelling | doaj.art-efc20a7303c74cdcbe326752c5355ae62022-12-21T18:39:21ZengElsevierJournal of Global Antimicrobial Resistance2213-71652021-09-0126117127Antimicrobial activity of manogepix, a first-in-class antifungal, and comparator agents tested against contemporary invasive fungal isolates from an international surveillance programme (2018–2019)Michael A. Pfaller0Michael D. Huband1Robert K. Flamm2Paul A. Bien3Mariana Castanheira4JMI Laboratories, North Liberty, IA, USA; University of Iowa, Iowa City, IA, USAJMI Laboratories, North Liberty, IA, USA; Corresponding author. Mailing address: JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317, USA. Tel.: +1 319 665 3370; fax: +1 319 665 3371.JMI Laboratories, North Liberty, IA, USAAmplyx Pharmaceuticals, San Diego, CA, USAJMI Laboratories, North Liberty, IA, USAABSTRACT: 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.http://www.sciencedirect.com/science/article/pii/S2213716521001119ManogepixAntifungalGwt1CLSIEUCAST |
| spellingShingle | Michael A. Pfaller Michael D. Huband Robert K. Flamm Paul A. Bien Mariana Castanheira 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) Journal of Global Antimicrobial Resistance Manogepix Antifungal Gwt1 CLSI EUCAST |
| title | 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) |
| title_full | 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) |
| title_fullStr | 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) |
| title_full_unstemmed | 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) |
| title_short | 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) |
| title_sort | 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 |
| topic | Manogepix Antifungal Gwt1 CLSI EUCAST |
| url | http://www.sciencedirect.com/science/article/pii/S2213716521001119 |
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