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We have previously reported thatCryptococcus neoformans strains are innately heteroresistant to fluconazolein vitro , producing minor, highly resistant subpopulations due to adaptive formation of disomic chromosomes. Using a mouse model, we assessed the emergence of heteroresistant clones in the brain during fluconazole treatment and found that the occurrence of heteroresistant clonesin vivo with chromosomal disomy is strain dependent. Interestingly, emergence of heteroresistant clonesin vivo was unrelated to the strain's MIC to fluconazole.

antimicrobial agents and chemotherapy

Azole Heteroresistance in Cryptococcus neoformans: Emergence of Resistant Clones with Chromosomal Disomy in the Mouse Brain during Fluconazole Treatment