# In Vitro Evaluation of 5-Fluorouridine as an Adjuvant to Antifungal Drugs and Molecular Insights into Resistance to This Compound in Candida Species

## TL;DR

This study explores how 5-fluorouridine interacts with antifungal drugs against Candida species and finds that it can work well with certain drugs to fight infections.

## Contribution

The study identifies synergistic effects of 5-fluorouridine with antifungal drugs and links resistance to efflux pump activity in Candida strains.

## Key findings

- 5-fluorouridine showed antifungal activity against Candida strains with varying MIC values.
- Synergy was observed between 5-fluorouridine and fluconazole, voriconazole, or caspofungin in C. albicans isolates.
- Efflux pump inhibitors reduced resistance to 5-fluorouridine in certain Candida species.

## Abstract

This study evaluated the in vitro interaction of 5-fluorouridine (5-FUrd) with antifungal drugs and examined the role of efflux pumps in 5-FUrd resistance. Eleven reference Candida strains and twenty-three clinical C. albicans isolates from gynecological patients were tested. The antifungal activity of 5-FUrd alone and in combination with amphotericin B, fluconazole, voriconazole, caspofungin, and flucytosine was assessed using the checkerboard microdilution method. Efflux pump activity was evaluated using two inhibitors: carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and verapamil. 5-FUrd exhibited antifungal activity against both the reference and clinical Candida strains, with MIC values ranging from 0.1 µg/mL to 409.6 µg/mL. The checkerboard assays revealed primarily no interactions in the reference Candida strains, whereas the reference C. albicans and clinical C. albicans isolates showed notable synergy between 5-FUrd and fluconazole, voriconazole, or caspofungin. The efflux pump inhibitors reduced the MICs of 5-FUrd in the resistant strains of C. lusitaniae, C. kefyr, and particularly C. krusei, suggesting efflux-mediated resistance mechanisms. This study highlights the potential of 5-FUrd, alone or combined with azoles or caspofungin, as an adjunct therapy against Candida infections. It also suggests that reduced susceptibility may be linked to efflux pump activity in certain strains.