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Impact of milbemycin oxime on fluconazole resistance in Candida auris

Lola Aubry1, Danielle Brandalise1, Marine Louvet1

  • 1Institute of Microbiology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Jac-Antimicrobial Resistance
|April 14, 2025
PubMed
Abstract

Insights

Milbemycin oxime enhances fluconazole

Area of Science:

  • Mycology and Antimicrobial Resistance

Background:

  • Candida auris is a multidrug-resistant yeast, particularly to azole antifungals like fluconazole.
  • Azole resistance in C. auris is often mediated by efflux pumps, such as Cdr1.
  • Milbemycin oxime inhibits ABC transporters, potentially reversing azole resistance.

Purpose of the Study:

  • To evaluate the combined effect of milbemycin oxime and fluconazole against Candida auris.
  • To investigate the interaction in clinical and laboratory-generated C. auris isolates with diverse azole resistance mechanisms.

Main Methods:

  • Chequerboard assays were used to determine the fractional inhibitory concentration index (FICI) for drug interactions.
  • Activity of ABC transporters was measured using rhodamine 6g (R6G) fluorescence.
  • Experiments included clinical and laboratory-derived C. auris strains with known resistance mechanisms.

Main Results:

  • A synergistic interaction between milbemycin oxime and fluconazole was observed against most C. auris isolates.
  • Synergism was noted even in isolates with Cdr1-independent azole resistance mechanisms (e.g., ERG11 mutations).
  • Milbemycin oxime demonstrated inhibition of ABC transporters, confirmed by R6G experiments.

Conclusions:

  • Milbemycin oxime shows potential as an adjunctive therapy to overcome azole resistance in Candida auris.
  • The combination is particularly promising for C. auris strains exhibiting high CDR1 overexpression.

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