Activities of E1210 and Comparator Agents Tested by CLSI and EUCAST Broth Microdilution Methods against Fusarium and Scedosporium Species Identified Using Molecular Methods

Castanheira, Mariana; Duncanson, Frederick P.; Diekema, Daniel J.; Guarro, Josep; Jones, Ronald N.; Pfaller, Michael A.

doi:10.1128/aac.05414-11

Cited by 100Antifungal resistance and susceptibilityFungal Plant Pathogen ControlFungal Infections and Studies

Activities of E1210 and Comparator Agents Tested by CLSI and EUCAST Broth Microdilution Methods against Fusarium and Scedosporium Species Identified Using Molecular Methods

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Castanheira, Mariana, Duncanson, Frederick P., Diekema, Daniel J., Guarro, Josep, Jones, Ronald N., Pfaller, Michael A.·2012·Antimicrobial Agents and Chemotherapy

DOI 10.1128/aac.05414-11PMC PMC3256086

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Abstract

Fusarium ( n = 67) and Scedosporium ( n = 63) clinical isolates were tested by two reference broth microdilution (BMD) methods against a novel broad-spectrum (active against both yeasts and molds) antifungal, E1210, and comparator agents. E1210 inhibits the inositol acylation step in glycophosphatidylinositol (GPI) biosynthesis, resulting in defects in fungal cell wall biosynthesis. Five species complex organisms/species of Fusarium (4 isolates unspeciated) and 28 Scedosporium apiospermum , 7 Scedosporium aurantiacum , and 28 Scedosporium prolificans species were identified by molecular techniques. Comparator antifungal agents included anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B. E1210 was highly active against all of the tested isolates, with minimum effective concentration (MEC)/MIC 90 values (μg/ml) for E1210, anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B, respectively, for Fusarium of 0.12, >16, >16, >8, >8, 8, and 4 μg/ml. E1210 was very potent against the Scedosporium spp. tested. The E1210 MEC 90 was 0.12 μg/ml for S. apiospermum , but 1 to >8 μg/ml for other tested agents. Against S. aurantiacum , the MEC 50 for E1210 was 0.06 μg/ml versus 0.5 to >8 μg/ml for the comparators. Against S. prolificans , the MEC 90 for E1210 was only 0.12 μg/ml, compared to >4 μg/ml for amphotericin B and >8 μg/ml for itraconazole, posaconazole, and voriconazole. Both CLSI and EUCAST methods were highly concordant for E1210 and all comparator agents. The essential agreement (EA; ±2 doubling dilutions) was >93% for all comparisons, with the exception of posaconazole and F. oxysporum species complex (SC) (60%), posaconazole and S. aurantiacum (85.7%), and voriconazole and S. aurantiacum (85.7%). In conclusion, E1210 exhibited very potent and broad-spectrum antifungal activity against azole- and amphotericin B-resistant strains of Fusarium spp. and Scedosporium spp. Furthermore, in vitro susceptibility testing of E1210 against isolates of Fusarium and Scedosporium may be accomplished using either of the CLSI or EUCAST BMD methods, each producing very similar results.

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Manogepix has low MICs against Aspergillus species from sections Fumigati, Flavi, Terrei, and Nigri, Purpureocillium lilacinum, Cladosporium species, Phialophora species, Rhinocladiella aquaspersa, Fonsecaea pedrosoi, Scedosporium apiospermum, Scedosporium aurantiacum, Fusarium solani, and Lomentospora prolificans.
“Regarding in vitro activity against molds, low MICs against Aspergillus species from the Section Fumigati, Flavi, Terrei, and Nigri (Miyazaki et al., 2011; Pfaller et al., 2019), Purpureocillium lilacinum, Cladosporium species, Phialophora species, Rhinocladiella aquaspersa, Fonsecaea pedrosoi (Miyazaki et al., 2011), Scedosporium apiospermum, and Scedosporium aurantiacum (Castanheira et al., 2012”
From Fungal Cell Wall: Emerging Antifungals and Drug Resistance. (2019) · cites this paper as Castanheira et al., 2012
Fosmanogepix possesses broad in vitro activity against Candida (excluding C. krusei), Trichosporon, Coccidioides, Cryptococcus, Aspergillus (A. fumigatus, A. flavus, A. niger), and amphotericin B-resistant strains of Fusarium and Scedosporium.
“Fosmanogepix possesses broad in vitro activity against many genera of fungi: Candida (excluding C. krusei), Trichosporon, Coccidioides, Cryptococcus, Aspergillus (A. fumigatus, A. flavus, A. niger), as well as AmB-resistant strains of Fusarium and Scedosporium (Fig. 1) [51, 53–55].”
From Investigational Agents for the Treatment of Resistant Yeasts and Molds (2021) · cites this paper as [53]

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Authors: Castanheira, M., Duncanson, F. P., Diekema, D. J., Guarro, J., Jones, R. N., & Pfaller, M. A.
Affiliations: JMI Laboratories (US)
Eisai (United States) (US)
University of Iowa (US)
Institut de Recerca Biomèdica Catalunya Sud (ES)
Tufts University (US)
ORCID: Castanheira, Mariana
Diekema, Daniel J.
Guarro, Josep
Jones, Ronald N.
Pfaller, Michael A.
Venue: Antimicrobial Agents and Chemotherapy
Publisher: American Society for Microbiology
Published: 2012-01
Volume: 56
Issue: 1
Pages: 352-357
ISSN: 0066-4804 (ISSN-L)
1098-6596
DOI: 10.1128/aac.05414-11
PMC: PMC3256086
OpenAlex: W2014616328
Cited by: 98
References: 38
Citations by year: 2026: 8 · 2025: 3 · 2024: 6 · 2023: 7 · 2022: 9 · 2021: 12 · 2020: 11 · 2019: 15 · 2018: 9 · 2017: 7 · 2016: 4 · 2015: 4 · 2014: 1 · 2012: 2
FWCI: 0.65
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Antimicrobial Agents and Chemotherapy (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Eisai
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Keywords: antifungal susceptibility, Fusarium, Scedosporium, Scedosporium prolificans, Scedosporium apiospermum, Scedosporium aurantiacum, cell wall biosynthesis, minimum effective concentration, antifungal agents, anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, amphotericin B
MeSH terms: Caspofungin, Anidulafungin, Acylation, Aminopyridines, Amphotericin B, Antifungal Agents, Fusarium, Humans, Inositol, Isoxazoles, Microbial Sensitivity Tests, Pyrimidines, Triazoles, Glycosylphosphatidylinositols, Itraconazole, Scedosporium, Echinocandins, Lipopeptides, Voriconazole

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Activities of E1210 and Comparator Agents Tested by CLSI and EUCAST Broth Microdilution Methods against Fusarium and Scedosporium Species Identified Using Molecular Methods

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