In Vitro Interaction of Geldanamycin with Triazoles and Echinocandins Against Common and Emerging Candida Species

  • Shahram Mahmoudi
  • Sassan Rezaie
  • Roshanak Daie Ghazvini
  • Seyed Jamal Hashemi
  • Hamid Badali
  • Alireza Foroumadi
  • Kambiz Diba
  • Anuradha Chowdhary
  • Jacques F. Meis
  • Sadegh KhodavaisyEmail author
Original Article


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.


Candida auris Drug synergism Drug interactions Drug resistance Hsp90 heat shock proteins 



The authors would like to thank Dr. Hossein Zarrinfar for his assistance during the study.


This work was financially supported by Tehran University of Medical Sciences, Tehran, Iran (Grant No. 9421353001).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

Not applicable.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Shahram Mahmoudi
    • 1
    • 2
  • Sassan Rezaie
    • 1
  • Roshanak Daie Ghazvini
    • 1
  • Seyed Jamal Hashemi
    • 1
    • 3
  • Hamid Badali
    • 4
  • Alireza Foroumadi
    • 5
  • Kambiz Diba
    • 6
  • Anuradha Chowdhary
    • 7
  • Jacques F. Meis
    • 8
    • 9
  • Sadegh Khodavaisy
    • 1
    Email author
  1. 1.Department of Medical Parasitology and Mycology, School of Public HealthTehran University of Medical SciencesTehranIran
  2. 2.Students’ Scientific Research CenterTehran University of Medical SciencesTehranIran
  3. 3.Food Microbiology Research CenterTehran University of Medical SciencesTehranIran
  4. 4.Department of Medical Mycology /Invasive Fungi Research Center, School of MedicineMazandaran University of Medical SciencesSariIran
  5. 5.Department of Medicinal Chemistry, Faculty of Pharmacy and The Institute of Pharmaceutical Sciences (TIPS)Tehran University of Medical SciencesTehranIran
  6. 6.Department of Medical Parasitology and Mycology, Faculty of MedicineUrmia University of Medical SciencesUrmiaIran
  7. 7.Department of Medical Mycology, Vallabhbhai Patel Chest InstituteUniversity of DelhiDelhiIndia
  8. 8.Center of Expertise in MycologyRadboud University Medical Centre/Canisius Wilhelmina Hospital and Excellence Center for Medical Mycology of the European Confederation of Medical Mycology (ECMM)NijmegenThe Netherlands
  9. 9.Department of Medical Microbiology and Infectious DiseasesCanisius Wilhelmina HospitalNijmegenNetherlands

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