Antifungal Resistance in Cryptococcal Infections
Márcia de Souza Carvalho Melhem, Diniz Pereira Leite Júnior, Juliana Possatto Fernandes Takahashi, Milena Bronze Macioni, Lidiane de Oliveira, Lisandra Siufi Araujo, Wellington Santos Fava, Lucas Xavier Bonfietti, Anamaria Mello Miranda Paniago, James Venturini, Ana Espinel‐Ingroff
Abstract
Antifungal therapy, especially with the azoles, could promote the incidence of less susceptible isolates of Cryptococcus neoformans and C. gattii species complexes (SC), mostly in developing countries. Given that these species affect mostly the immunocompromised host, the infections are severe and difficult to treat. This review encompasses the following topics: 1. infecting species and their virulence, 2. treatment, 3. antifungal susceptibility methods and available categorical endpoints, 4. genetic mechanisms of resistance, 5. clinical resistance, 6. fluconazole minimal inhibitory concentrations (MICs), clinical outcome, 7. environmental influences, and 8. the relevance of host factors, including pharmacokinetic/pharmacodynamic (PK/PD) parameters, in predicting the clinical outcome to therapy. As of now, epidemiologic cutoff endpoints (ECVs/ECOFFs) are the most reliable antifungal resistance detectors for these species, as only one clinical breakpoint (amphotericin B and C. neoformans VNI) is available.