Increased Antifungal Drug Resistance in Clinical Isolates of Cryptococcus neoformans in Uganda

Abstract

Cryptococcal antigen screening is recommended among people living with AIDS when entering HIV care with a CD4 count of 50 of 4 μg/ml and an MIC ₉₀ of 8 μg/ml prior to widespread human fluconazole and agricultural azole fungicide usage, we report an upward shift in the fluconazole MIC ₅₀ to 8 μg/ml and an MIC ₉₀ value of 32 μg/ml, with 31% of isolates with a fluconazole MIC of ≥16 μg/ml. We observed an amphotericin B MIC ₅₀ of 0.5 μg/ml and an MIC ₉₀ of 1 μg/ml, of which 99.5% of isolates (197 of 198 isolates) were still susceptible. No correlation between MIC and clinical outcome was observed in the context of amphotericin B and fluconazole combination induction therapy. We also analyzed Cryptococcus susceptibility to sertraline, with an MIC ₅₀ of 4 μg/ml, suggesting that sertraline is a promising oral, low-cost, available, novel medication and a possible alternative to fluconazole. Although the CLSI broth microdilution assay is ideal to standardize results, limit human bias, and increase assay capacity, such assays are often inaccessible in low-income countries. Thus, we also developed and validated an assay that could easily be implemented in a resource-limited setting, with similar susceptibility results ( P = 0.52).