Candidemia: Evolution of Drug Resistance and Novel Therapeutic Approaches.

Candidemia and invasive candidiasis are the most common healthcare-associated invasive fungal infections, with a crude mortality rate of 25-50%. remains the most frequent etiology, followed by and . With the exception of a limited number of species (ie: and rare species), resistance to fluconazole and other triazoles are quite uncommon. However, recently fluconazole-resistant , echinocandin-resistant and the multidrug resistant have emerged. Resistance to amphotericin B is even more rare due to the reduced fitness of resistant isolates. The mechanisms of antifungal resistance in (altered drug-target interactions, reduced cellular drug concentrations, and physical barriers associated with biofilms) are analyzed. The choice of the antifungal therapy for candidemia must take into account several factors such as type of patient, presence of devices, severity of illness, recent exposure to antifungals, local epidemiology, organs involvement, and species. The first-line therapy in non-neutropenic critical patient is an echinocandin switching to fluconazole in clinically stable patients with negative blood cultures and azole susceptible isolate. Similarly, an echinocandin is the drug of choice also in neutropenic patients. The treatment duration is 14 days after the first negative blood culture or longer in cases of organ involvement. An early removal of vascular catheter improves the outcome. The promising results of new antifungal molecules, such as the terpenoid derivative ibrexafungerp, the novel echinocandin with an enhanced half-life rezafungin, oteseconazole and fosmanogepix, representative of new classes of antifungals, are discussed.