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In Vitro Interaction of Geldanamycin With Triazoles and Echinocandins Against Common and Emerging Candida Species Publisher Pubmed



Mahmoudi S1, 2 ; Rezaie S1 ; Daie Ghazvini R1 ; Hashemi SJ1, 3 ; Badali H4 ; Foroumadi A5 ; Diba K6 ; Chowdhary A7 ; Meis JF8, 9 ; Khodavaisy S1
Authors
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Authors Affiliations
  1. 1. Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Food Microbiology Research Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Medical Mycology /Invasive Fungi Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
  5. 5. Department of Medicinal Chemistry, Faculty of Pharmacy and The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Medical Parasitology and Mycology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
  7. 7. Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India
  8. 8. Center of Expertise in Mycology, Radboud University Medical Centre/Canisius Wilhelmina Hospital and Excellence Center for Medical Mycology of the European Confederation of Medical Mycology (ECMM), Nijmegen, Netherlands
  9. 9. Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, Netherlands

Source: Mycopathologia Published:2019


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. © 2019, Springer Nature B.V.