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. 2022 May 16:12:906563.
doi: 10.3389/fcimb.2022.906563. eCollection 2022.

In Vitro Antifungal Activity of Ibrexafungerp (SCY-078) Against Contemporary Blood Isolates From Medically Relevant Species of Candida: A European Study

Guillermo Quindós  1 , Katherine Miranda-Cadena  1 , Rosario San-Millán  1 , Katyna Borroto-Esoda  2 , Emilia Cantón  3 , María José Linares-Sicilia  4 , Axel Hamprecht  5 , Isabel Montesinos  6 , Anna Maria Tortorano  7 , Anna Prigitano  7 , Matxalen Vidal-García  8 , Cristina Marcos-Arias  1 , Andrea Guridi  1 , Ferran Sanchez-Reus  9 , Jesús Machuca-Bárcena  10 , Manuel Antonio Rodríguez-Iglesias  10 , Estrella Martín-Mazuelos  11 , Carmen Castro-Méndez  11 , Leyre López-Soria  12 , Alba Ruiz-Gaitán  3 , Marcelo Fernandez-Rivero  3 , Damaris Lorenzo  13 , Javier Capilla  13 , Antonio Rezusta  8 , Javier Pemán  3 , Josep Guarro  13 , Joana Pereira  14 , Célia Pais  14 , Orazio Romeo  15 , Guillermo Ezpeleta  16 , Nerea Jauregizar  17 , David Angulo  2 , Elena Eraso  1
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In Vitro Antifungal Activity of Ibrexafungerp (SCY-078) Against Contemporary Blood Isolates From Medically Relevant Species of Candida: A European Study

Guillermo Quindós et al. Front Cell Infect Microbiol. .

Abstract

Background: Ibrexafungerp (SCY-078) is the newest oral and intravenous antifungal drug with broad activity, currently undergoing clinical trials for invasive candidiasis.

Objective: The aim of this study was to assess the in vitro activity of ibrexafungerp and comparators against a collection of 434 European blood isolates of Candida.

Methods: Ibrexafungerp, caspofungin, fluconazole, and micafungin minimum inhibitory concentrations (MICs) were collected from 12 European laboratories for 434 blood isolates, including 163 Candida albicans, 108 Candida parapsilosis, 60 Candida glabrata, 40 Candida tropicalis, 29 Candida krusei, 20 Candida orthopsilosis, 6 Candida guilliermondii, 2 Candida famata, 2 Candida lusitaniae, and 1 isolate each of Candida bracarensis, Candida catenulata, Candida dubliniensis, and Candida kefyr. MICs were determined by the EUCAST broth microdilution method, and isolates were classified according to recommended clinical breakpoints and epidemiological cutoffs. Additionally, 22 Candida auris from different clinical specimens were evaluated.

Results: Ibrexafungerp MICs ranged from 0.016 to ≥8 mg/L. The lowest ibrexafungerp MICs were observed for C. albicans (geometric MIC 0.062 mg/L, MIC range 0.016-0.5 mg/L) and the highest ibrexafungerp MICs were observed for C. tropicalis (geometric MIC 0.517 mg/L, MIC range 0.06-≥8 mg/L). Modal MICs/MIC50s (mg/L) against Candida spp. were 0.125/0.06 for C. albicans, 0.5/0.5 for C. parapsilosis, 0.25/0.25 for C. glabrata, 0.5/0.5 for C. tropicalis, 1/1 for C. krusei, 4/2 for C. orthopsilosis, and 0.5/0.5 for C. auris. Ibrexafungerp showed activity against fluconazole- and echinocandin-resistant isolates. If adopting wild-type upper limits, a non-wild-type phenotype for ibrexafungerp was only observed for 16/434 (3.7%) isolates: 11 (4.6%) C. parapsilosis, 4 (5%) C. glabrata, and 1 (2.5%) C. tropicalis.

Conclusion: Ibrexafungerp showed a potent in vitro activity against Candida.

Keywords: Candida; EUCAST; SCY-078; antifungal resistance; antifungal testing; caspofungin; ibrexafungerp; micafungin.

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Conflict of interest statement

Outside the current study, we declare the following potential conflicts: GQ has received research grants from Astellas Pharma, Pfizer, Merck Sharp & Dohme, and SCYNEXIS. GQ has served on advisory/consultant boards for Merck, Sharp & Dohme, and SCYNEXIS, and he has received speaker honoraria from Abbvie, Astellas Pharma, Merck Sharp & Dohme, Pfizer, and SCYNEXIS. KB-E and DA are employed by SCYNEXIS. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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