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In this study, we found that ambroxol hydrochloride (128 μg/mL) exhibits synergistic antifungal effects in combination with fluconazole (2 μg/mL) against resistant planktonic  Candida albicans  ( C. albicans ) cells. This combination also exhibited synergistic effects against resistant  C. albicans  biofilms in different stages (4, 8, and 12 h) according to the microdilution method.  In vitro  data were further confirmed by the success of this combination in treating  Galleria mellonella  infected by resistant  C. albicans . With respect to the synergistic mechanism, our result revealed that ambroxol hydrochloride has an effect on the drug transporters of resistant  C. albicans , increasing the uptake and decreasing the efflux of rhodamine 6G, a fluorescent alternate of fluconazole. This is the first study to investigate the  in vitro  and  in vivo  antifungal effects, as well as the possible synergistic mechanism of ambroxol hydrochloride in combination with fluconazole against resistant  C. albicans . The results show the potential role for this drug combination as a therapeutic alternative to treat resistant  C. albicans  and provide insights into the development of antifungal targets and new antifungal agents.

Ambroxol Hydrochloride Combined with Fluconazole Reverses the Resistance of Candida albicans to Fluconazole