Current Perspectives on Antifungal Drug Resistance

Fungal infections are the fourth leading cause of nosocomial blood stream infections. The widespread application of antifungal drugs such as triazoles in AIDS and cancer patients promotes selection of resistant organisms by either inducing resistant subspecies of normally susceptible organisms like C. albicans or shifting colonization to more intrinsically resistant species. The association between prior exposure and subsequent triazole resistance in Candida spp. is of concern because of the prevalent use of triazole drugs for prophylaxis and preemptive therapy in patients at risk for systemic fungal infections.

The molecular mechanisms responsible for triazole resistance include direct modification of the triazole drug target enzyme, lanosterol 140-alpha-demethylase, and reduction in cellular drug accumulation due to overexpression of drug efflux transporters. Triazole resistance is also observed in invasive fungal pathogens, such as Cryptococcus neoformans and Aspergillus fumigatus, which appear to use similar resistance mechanisms. Finally, newer drug classes such as the echinocandins also show reduced drug susceptibility, albeit at a lower frequency than triazole drugs.

David Perlin is Scientific Director of the Public Health Research Institute (PHRI), a 63-year-old biomedical research organization that specializes in infectious diseases research. His laboratory studies the molecular basis for clinical resistance to antifungal drugs and helps develop rapid diagnostic approaches for fungal pathogens, agents of bioterrorism, and new disease agents like the SARS coronavirus.

Dr. Perlin is a member of the Executive Committee of the Northeast Biodefense Center and the New York City DOH Advisory Panel on Biodefense. He serves on NIH review panels, is on the editorial board of a number of biomedical research journals, and is a member of Senator Jon Corzine’s New Jersey Healthcare Taskforce.