Infection and Drug Resistance (Dec 2021)
Candidemia: Evolution of Drug Resistance and Novel Therapeutic Approaches
Abstract
Anna Maria Tortorano,1 Anna Prigitano,1 Gianluca Morroni,2 Lucia Brescini,2,3 Francesco Barchiesi2,4 1Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milano, Italy; 2Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, Ancona, Italy; 3Clinic of Infectious Diseases, Azienda Ospedaliero Universitaria, Ospedali Riuniti Umberto I-Lancisi-Salesi, Ancona, Italy; 4Clinic of Infectious Diseases, Azienda Ospedaliera Ospedali Riuniti Marche Nord, Pesaro, ItalyCorrespondence: Anna Maria TortoranoDepartment of Biomedical Sciences for Health, Università degli Studi di Milano, Via Pascal 36, Milano, 20133, ItalyTel +39 02 50315145Fax +39 02 50315146Email [email protected]: Candidemia and invasive candidiasis are the most common healthcare-associated invasive fungal infections, with a crude mortality rate of 25– 50%. Candida albicans remains the most frequent etiology, followed by C. glabrata, C. parapsilosis and C. tropicalis. With the exception of a limited number of species (ie: C. krusei, C. glabrata and rare Candida species), resistance to fluconazole and other triazoles are quite uncommon. However, recently fluconazole-resistant C. parapsilosis, echinocandin-resistant C. glabrata and the multidrug resistant C. auris have emerged. Resistance to amphotericin B is even more rare due to the reduced fitness of resistant isolates. The mechanisms of antifungal resistance in Candida (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 Candida 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.Keywords: candidemia, Candida, antifungal resistance, management of candidemia, novel antifungals
