The Bottom Line: In a 2010 study analyzing 71 Crytococcus gattii strands, it was found that all strains of C. gattii manifested heteroresistance, with a level of heteroresistance to fluconazole (LHF) that ranged between 4ug/ml and 32 ug/ml. A considerably higher proportion of the C. gattii strains (86%) than Cryptococcus neoformans strains (46%) exhibited LHFs that were > 16ug/ml.
Summary: Cryptococcosis is caused by two species, Cryptococcus neoformans and Cryptococcus gattii; fluconazole (FLC), a triazole, is widely used for the treatment of cryptococcosis regardless of the causative species. The strains with high LHFs were more virulent in mice and more resistant to xenobiotics that are unrelated to fluconazole, as reported for C. neoformans. However, the degree of resistance to xenobiotics in the C. gattii strains with high LHFs was significantly higher than that for the strains of C. neoformans with high LHFs.
Reference: Varma A. and Kwon-Chung KJ. “Heteroresistance of Cryptococcus gattii to fluconazole.” Antimicrobial Agents and Chemotherapy 2010; 54(6): 2303-2311.