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Identification of Off-Patent Compounds That Present Antifungal Activity Against the Emerging Fungal Pathogen Candida

Haroldo Cesar de Oliveira1,2, Maria Candida Monteiro1, Suélen Andreia Rossi1

  • 1Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain.

Frontiers in Cellular and Infection Microbiology
|April 20, 2019
PubMed

Insights

Drug repurposing identified new antifungal agents against the challenging pathogen Candida auris. Seven FDA-approved drugs showed activity, with synergistic effects noted for suloctidil and ebselen combinations.

Area of Science:

  • Mycology
  • Infectious Diseases
  • Pharmacology

Background:

  • Candida auris is a significant global health threat, causing difficult-to-treat hospital outbreaks.
  • C. auris exhibits resistance to common antifungal drugs like azoles and echinocandins, necessitating novel therapeutic strategies.

Purpose of the Study:

  • To identify existing FDA-approved drugs with antifungal activity against Candida auris through drug repurposing.
  • To evaluate the efficacy of identified compounds and their synergistic potential in combination therapies.

Main Methods:

  • Screening of 1,280 compounds from the Prestwick chemical library against three C. auris strains.
  • Determination of Minimum Inhibitory Concentrations (MICs) using the EUCAST protocol for active compounds.
  • Assessment of drug synergy using sub-inhibitory concentrations and Fractional Inhibitory Concentration Index (FICI).

Main Results:

  • 27 compounds inhibited C. auris growth in initial screening; 7 demonstrated confirmed antifungal activity with MICs from 0.5 to 64 mg/L.
  • Significant synergistic interactions were observed between suloctidil and voriconazole (FICI 0.11-0.5).
  • Synergistic effects were also found between ebselen and anidulafungin (FICI 0.12-0.44).

Conclusions:

  • Drug repurposing is a promising strategy for developing new treatments against Candida auris infections.
  • Several FDA-approved drugs show potential as novel antifungal agents for C. auris.
  • Combinations of existing drugs may enhance treatment efficacy and overcome resistance mechanisms.
Keywords:
Candida aurisantifungalsdrug repurposingmultiresistancesynergism

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