بررسی اثر ضد قارچی پاروکستین به تنهایی و در ترکیب با فلوکونازول بر روی جدایه‌های کاندیدا آلبیکانس مقاوم به فلوکونازول در محیط آزمایشگاه

Introduction: Fungal infections caused by Candida albicans present a significant clinical challenge due to complex resistance mechanisms. Drug repositioning has emerged as a promising strategy to overcome antifungal resistance. This study aimed to investigate the antifungal efficacy of paroxetine, alone and in combination with fluconazole, against clinical isolates of fluconazole-resistant C. albicans.
Materials & Methods: In this in vitro experimental study, the Minimum Inhibitory Concentration (MIC) of paroxetine and fluconazole was determined, both individually and in combination, using the broth microdilution method according to CLSI guidelines. Drug interaction was evaluated by calculating the Fractional Inhibitory Concentration Index (FICI), and statistical significance was analyzed using appropriate tests.
Results: Results demonstrated that paroxetine possesses intrinsic antifungal activity against resistant strains. When combined with fluconazole, the addition of sub-inhibitory concentrations of paroxetine led to a significant reduction in the mean MIC of fluconazole (P<0.001). Analysis of the FICI revealed that a synergistic effect (FICI ≤ 0.5) occurred in a subset of isolates, while an "indifferent" interaction pattern was observed in others; no antagonistic effects were reported in this study.
Conclusion: Paroxetine exhibits not only intrinsic antifungal activity but also potential synergistic effects with fluconazole in restoring sensitivity in resistant C. albicans isolates. This combination could be considered a potential adjuvant therapeutic strategy for managing resistant fungal infections. Further molecular studies are recommended to elucidate the precise mechanisms underlying this synergy.