Antifungal resistance: Cellular and molecular mechanisms

Abstract

The incidence of life-threatening fungal infections, a critical public health threat, has dramatically increased, and infections due to resistant strains represent a therapeutic drug selection challenge. Although MICs are not the best predictors of patient response to therapy and clinical breakpoints are still not available for all licensed agent/species combinations, susceptibility testing remains the most practical tool for in vitro resistance detection. Some fungal species may be inherently resistant to an antifungal; however, the increasing use of antifungal prophylactic and empirical treatments has led to the emergence of resistance. The overexpression of genes encoding proteins of biosynthetic pathways or efflux pumps and modifications of target enzyme(s) represent the most relevant molecular mechanisms involved in fungal resistance. The cellular and molecular mechanisms responsible for antifungal and multidrug in vitro resistance will be reviewed in this chapter as well as their impact in patient care.