Mahmoudi, Shahram ; Rezaie, Sassan ; Daie Ghazvini, Roshanak ; Hashemi, Seyed Jamal ; Badali, Hamid ; Foroumadi, Alireza ; Diba, Kambiz ; Chowdhary, Anuradha ; Meis, Jacques F. ; Khodavaisy, Sadegh (2019) In Vitro Interaction of Geldanamycin with Triazoles and Echinocandins Against Common and Emerging Candida Species Mycopathologia, 184 (5). pp. 607-613. ISSN 0301-486X
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Official URL: http://doi.org/10.1007/s11046-019-00370-7
Related URL: http://dx.doi.org/10.1007/s11046-019-00370-7
Abstract
The aim of this study was to determine the in vitro interactions of geldanamycin (Hsp90-inhibitor) with triazoles and echinocandins against common and emerging Candida species. Twenty clinically important Candida strains comprising C. auris, C. albicans, C. parapsilosis, and C. glabrata (each five strains) were included. In vitro interactions of geldanamycin with fluconazole, itraconazole, caspofungin and anidulafungin were determined using a checkerboard method. The results were interpreted as synergistic, indifferent and antagonistic based on the fractional inhibitory concentration index (FICI). In vitro combination of fluconazole with geldanamycin resulted in synergistic effect against C. albicans (100%), C. glabrata (80%) and C. parapsilosis (80%) (FICI range 0.009–0.5), while indifferent interactions were obtained against C. auris (FICI range 1.5–2). The overall minimum inhibitory concentration (MIC) range of fluconazole against C. albicans, C. glabrata and C. parapsilosis reduced from 16–256 to 0.25–64 mg/L when combined with geldanamycin. Regarding the synergistic effect of geldanamycin with itraconazole against all strains of C. albicans, C. glabrata and C. parapsilosis (FICI range 0.009–0.375), the MIC range of this antifungal was reduced from 0.125-32 mg/L when tested alone, to 0.03–1 mg/L. Combinations of geldanamycin with fluconazole and itraconazole against C. auris, as well as combination of geldanamycin with caspofungin and anidulafungin against all studied Candida species, resulted in indifferent effects. No antagonism was observed. Simultaneous targeting of Hsp90 and lanosterol 14-α demethylase seems an effective approach against C. albicans, C. glabrata and C. parapsilosis. However, this combination is ineffective against the emerging pathogen C. auris.
Item Type: | Article |
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Source: | Copyright of this article belongs to Springer Nature Switzerland AG. |
Keywords: | Candida auris; Drug Synergism; Drug Interactions; Drug Resistance; Hsp90 Heat Shock Proteins. |
ID Code: | 117338 |
Deposited On: | 19 Apr 2021 09:56 |
Last Modified: | 19 Apr 2021 09:56 |
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