In vitro activity of isavuconazole against azole-resistant environmental Aspergillus fumigatus isolates, cryptic Candida strains and emerging yeasts

Patrice Le Pape


Background: Isavuconazole is a novel broad-spectrum triazole agent. Since October 2015,
isavuconazole is approved in Europe for the treatment of adult patients with invasive aspergillosis or
mucormycosis when amphotericin B is inappropriate. Isavuconazole has in vitro activity against most
medically important fungi, including species of Candida, Aspergillus, and Cryptococcus and activity
against some of the agents of mucormycosis. Considering that isavuconazole shares the same
mechanism of action with the other triazoles, cross-resistance is an important concern in the class.
The aim of this study was to complete the isavuconazole spectrum establishing MIC for rare azoleresistant
environmental Aspergillus strains, fluconazole resistant Candida spp and uncommon fungi by
using EUCAST methodology.
Material/methods: A collection of wild-type A. fumigatus clinical isolates and environmental
(TR34/L98H and TR46/Y121F/T289A) azole-resistant A. fumigatus isolates was evaluated for
isavuconazole (Basilea Pharmaceutica Ltd) MIC determination by EUCAST standard methodology.
Additionally, fluconazole resistant Candida spp, cryptic Candida species (C. metapsilosis, C.
nivariensis, C. auris, C. africana) and other uncommon yeasts (Trichosporon faecale, Cryptococcus
gattii, Galactomyces candidus, Saprochaete suaveolens, Pichia kluyveri) were also studied. Candida
krusei ATCC 6258 and C. parapsilosis ATCC 22019 were used as control strains. For azole resistant
Aspergillus and Candida isolates, isavuconazole was docked in the models of caCYP51 and
Results: In this study isavuconazole demonstrated excellent in vitro activity against the crytic species
C. metapsilosis, C. nivariensis, C. auris and C. africana and all the emerging yeasts. Furthermore this
antifungal drug exhibited low MICs against Candida spp isolates including isolates with reduced
fluconazole and/or voriconazole susceptibility as against wild type Aspergillus fumigatus. However,
environmental azole-resistant A. fumigatus isolates also show high MICs (>8ug/ml) to isavuconazole.
Conclusions: In conclusion, the in vitro data presented in this study provide encouraging evidence of
isavuconazole activity against unusual fungal pathogens and further contribute to outline its spectrum
of activity. However, isavuconazole did not reverse resistance of TR34/L98H and TR46/Y121F/T289A
isolates. Although this agent may be useful in the treatment of the rare yeasts, clinical data are
needed to confirm these results.


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26th European Congress of Clinical Microbiology and Infectious Diseases
    • ECCMID 26th (2016)