In Vitro Antifungal Effects of Duloxetine in Combination with Fluconazole on Fluconazole-Resistant Candida Albicans

Aim: This study evaluate the antifungal effects of duloxetine as monotherapy and in combination with fluconazole on fluconazole-resistant C. albicans. Methods: In this in vitro study, a suspension of fluconazole-resistant C. albicans clinical isolates from oral candidiasis was prepared using the CLSI M۳۷-A۳ method. Fluconazole (۳ mg/mL) and duloxetine (۱۶۰ µg/mL) stock solutions were serially diluted ۹ times (۰.۶۲۵-۱۶۰ µg/mL for duloxetine and ۰.۵-۱۲۸ µg/mL for fluconazole). Their antifungal activity against C. albicans were evaluated by the microdilution method through broth media. The minimum inhibitory concentration of duloxetine, fluconazole, and their combination was also determined. Results: Fluconazole-resistant C. albicans was only sensitive to ۳۲, ۶۴, and ۱۲۸ µg/mL fluconazole and ۱۶۰, ۸۰, and ۴۰ µg/mL duloxetine as monotherapy. It was also sensitive to ۸۰ and ۱۶۰ µg/mL duloxetine combined with all ۹ dilutions of fluconazole, but ۴۰ µg/mL duloxetine was only effective in combination with ۱۶ to ۱۲۸ µg/mL fluconazole. Fluconazole-resistant C. albicans was sensitive to ۱۰ and ۲۰ µg/mL duloxetine combined with ۳۲, ۶۴, and ۱۲۸ µg/mL fluconazole. It was also sensitive to ۰.۶۲۵, ۱.۲۵, ۲.۵, and ۵ µg/mL duloxetine combined with ۶۴ and ۱۲۸ µg/mL fluconazole. The MIC of duloxetine was ۴۰ µg/mL as monotherapy and ۱۶ µg/mL combined with fluconazole. Conclusion: Duloxetine had antifungal effects and the combination of duloxetine with fluconazole had synergistic effects on inhibited fluconazole -resistant C. albicans

کلیدواژه ها:

Candida Albicans ، Fluconazole ، Duloxetine