Investigation of the antifungal activity of panobinostat, tamoxifen, and miltefosine alone and in combination with some conventional antifungal drugs against fluconazole-resistant Candida species

Background and Objectives: The increasing incidence of antifungal-resistant Candida infections, particularly among can- cer patients, emphasizes the urgency of exploring alternative therapeutic strategies. This study aimed to assess the in vitro antifungal efficacy of three anticancer agents—tamoxifen, panobinostat, and miltefosine—both individually and in combina- tion with the antifungals fluconazole and itraconazole, against fluconazole-resistant Candida strains. Materials and Methods: A total of 21 clinical Candida isolates (C. albicans, C. parapsilosis, C. glabrata, C. tropicalis, and C. auris) were evaluated. Antifungal susceptibility testing was conducted following the microdilution protocol outlined by CLSI. Results: The combination of panobinostat with fluconazole exhibited full synergistic activity against C. albicans and C. tropicalis. Conversely, antagonistic effects were observed with C. parapsilosis and C. glabrata, while C. auris displayed an indifferent response. Panobinostat paired with itraconazole showed synergy exclusively against C. albicans. Similarly, miltefosine combined with itraconazole demonstrated synergism with C. albicans, but no interaction was found with fluco- nazole. Tamoxifen in conjunction with itraconazole revealed a synergistic response against C. albicans, antagonism with C. tropicalis, and indifference with other species. Conclusion: Certain combinations of antifungals and anticancer agents could potentiate antifungal activity against resistant Candida isolates. Therefore, precise species-level identification is vital for tailoring effective combination therapies, partic- ularly in immunocompromised individuals.