Fluconazole in combination with compounds of natural and pharmaceutical origin: A study on their antimicrobial...

Candidiasis is a prevalent and clinically significant fungal infection. Candida auris has emerged as an important etiological agent due to its high transmissibility, potential to cause severe infections, and resistance to multiple antifungal drugs. Combining fluconazole with other compounds to achieve additive or synergistic antifungal effects has been proposed as a promising strategy for managing these infections.

This study aimed to evaluate the antifungal effects of fluconazole in combination with seven natural compounds (berberine chloride, caffeic acid phenethyl ester, catechin monohydrate, epigallocatechin gallate, magnolol, osthole, and quercetin hydrate) and seven drugs (amiodarone, amlodipine, budesonide, doxycycline, ibuprofen, minocycline, and tigecycline) against C. auris.

The antifungal activity of fluconazole alone and in combination with selected compounds and drugs was analyzed to identify additive or synergistic interactions against 21 isolates of C. auris. Minimum inhibitory concentrations (MICs) of fluconazole were determined and compared across combinations.

Fluconazole combined with magnolol, caffeic acid phenethyl ester, or quercetin hydrate showed additive effects against 38%, 9.5%, and 2% of isolates, respectively, and a synergistic effect with quercetin hydrate in 19% of isolates. Fluconazole MICs were reduced from >64μg/mL to 1-16μg/mL with magnolol in 19 isolates, to 1-32μg/mL with caffeic acid phenethyl ester in 17 isolates, and to 1-2μg/mL with quercetin hydrate in 8 isolates.

These findings highlight the potential of fluconazole combined with magnolol, caffeic acid phenethyl ester, or quercetin hydrate for managing C. auris infections. Further in vivo studies are warranted to assess their therapeutic applicability.