? Fungal infections caused by Candida spp. represent a significant cause of morbidity and mortality for severely ill patients. The widespread use of antifungal agents has resulted in the selection of naturally resistant Candida species, as well as expression of resistance from previously susceptible species resulting from genetic mutations and/or selection of resistant subpopulations. Several mechanisms have been linked to antifungal resistance, including mutations that alter drug-target interactions and reduced drug accumulation by overexpression of drug efflux pumps. The care of critically-ill patients requires a rapid identification of fungal pathogens with an assessment of antifungal susceptibility. Nucleic acid-based amplification assays provide an optimal approach to this problem because they are more rapid and sensitive than current culture-based and biochemical methods. A series of Molecular Beacon-based diagnostic panels will be constructed that allow sensitive identification of fungal pathogens with a rapid assessment of antifungal drug resistance by examining prominent mechanisms. The panel will be constructed for Candida albicans, which accounts for a majority of fungal infections, and will target resistance mechanisms for azole-based drugs and the new echinocandin class of antifungal agents. An important feature of the test panels will be allele discrimination, which will enable mutations resulting in drug resistance to be easily detected in the diploid (multiploid) Candida albicans. The major impact of the test panel will be rapid detection of drug resistance that can speed diagnosis and guide treatment decisions for life-threatening illnesses. Although our emphasis is on fungal infections, this approach should serve as a paradigm for applications to other pathogens with established resistance mechanisms. ? ?
| Perlin, David S (2011) Current perspectives on echinocandin class drugs. Future Microbiol 6:441-57 |
| Perlin, David S (2009) Antifungal drug resistance: do molecular methods provide a way forward? Curr Opin Infect Dis 22:568-73 |
