Activity of Isavuconazole and Other Azoles against Candida Clinical Isolates and Yeast Model Systems with Known Azole Resistance Mechanisms.

Détails

ID Serval
serval:BIB_3B9296518A78
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Activity of Isavuconazole and Other Azoles against Candida Clinical Isolates and Yeast Model Systems with Known Azole Resistance Mechanisms.
Périodique
Antimicrobial Agents and Chemotherapy
Auteur(s)
Sanglard D., Coste A.T.
ISSN
1098-6596 (Electronic)
ISSN-L
0066-4804
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
60
Numéro
1
Pages
229-238
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: epublish
Résumé
Isavuconazole is a novel, broad-spectrum, antifungal azole. In order to evaluate its interactions with known azole resistance mechanisms, isavuconazole susceptibility among different yeast models and clinical isolates expressing characterized azole resistance mechanisms was tested and compared to those of fluconazole, itraconazole, posaconazole, and voriconazole. Saccharomyces cerevisiae expressing the Candida albicans and C. glabrata ATP binding cassette (ABC) transporters (CDR1, CDR2, and CgCDR1), major facilitator (MDR1), and lanosterol 14-α-sterol-demethylase (ERG11) alleles with mutations were used. In addition, pairs of C. albicans and C. glabrata strains from matched clinical isolates with known azole resistance mechanisms were investigated. The expression of ABC transporters increased all azole MICs, suggesting that all azoles tested were substrates of ABC transporters. The expression of MDR1 did not increase posaconazole, itraconazole, and isavuconazole MICs. Relative increases of azole MICs (from 4- to 32-fold) were observed for fluconazole, voriconazole, and isavuconazole when at least two mutations were present in the same ERG11 allele. Upon MIC testing of azoles with clinical C. albicans and C. glabrata isolates with known resistance mechanisms, the MIC90s of C. albicans for fluconazole, voriconazole, itraconazole, posaconazole, and isavuconazole were 128, 2, 1, 0.5, and 2 μg/ml, respectively, while in C. glabrata they were 128, 2, 4, 4, and 16 μg/ml, respectively. In conclusion, the effects of azole resistance mechanisms on isavuconazole did not differ significantly from those of other azoles. Resistance mechanisms in yeasts involving ABC transporters and ERG11 decreased the activity of isavuconazole, while MDR1 had limited effect.
Pubmed
Web of science
Open Access
Oui
Création de la notice
01/03/2016 19:29
Dernière modification de la notice
20/08/2019 14:31
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