Drug Resistance in Cryptococcus: Epidemiology and Molecular Mechanisms
This chapter describes the epidemiology of antifungal drug resistance as identified by in vitro susceptibility testing and studies of the mechanisms of resistance in Cryptococcus neoformans and C. gattii. Taking into consideration the MIC distribution profiles for the various antifungal agents, the pharmacology of the antifungal drugs, and studies of resistance mechanisms and clinical outcomes, it is reasonable to adapt the breakpoints developed by the Clinical and Laboratory Standards Institute (CLSI) for Candida spp. for use in the discussion of antifungal resistance in C. neoformans and C. gattii. Resistance to flucytosine may develop from decreased uptake (loss of permease activity) or loss of enzymatic activity required for the conversion of flucytosine to 5-fluorouracil (cytosine deaminase) and 5-fluorouridylic acid (FUMP pyrophosphorylase). The echinocandin class of antifungals is relatively ineffective against Cryptococcus sp., but the mechanism of this resistance is still unknown. The epidemiology of antifungal resistance in the pathogenic cryptococci is a dynamic process that differs considerably according to the status of health care, especially that devoted to HIV and AIDS, in the region of interest. Improved understanding of the mechanisms of antifungal resistance in cryptococci will ultimately help in the battle against emerging resistance.
