Clinical impact of fluconazole-resistant

Fluconazole resistance in Candida parapsilosis is an increasing global concern, with resistance rates varying widely and reaching up to 80% in some regions. This trend has led to hospital outbreaks, primarily driven by mutations in the ERG11 gene, especially the Y132F substitution. The clinical relevance of fluconazole resistance remains controversial, as studies have yielded conflicting results regarding its impact on mortality. While some studies described an increased mortality associated with resistant strains, others reported no significant difference. Treatment options are limited: echinocandins and liposomal amphotericin B (L-AmB) are commonly used alternatives, but their use is challenged by intrinsic and emerging echinocandin resistance and L-AmB toxicity and cost. These limitations emphasize the need for robust antifungal stewardship and the development of new therapies. Novel agents such as rezafungin, fosmanogepix, and ibrexafungerp have shown promising activity against fluconazole-resistant C. parapsilosis, though further clinical studies are needed to confirm their efficacy. This narrative review aims to summarize current evidence on the epidemiology, clinical implications, and therapeutic approaches for fluconazole-resistant C. parapsilosis infections.