Background: Data regarding the antifungal susceptibility of Cryptococcus neoformans (CNE) isolates from The Netherlands are limited. We determined and compared the in vitro activity of the new azole antifungal drug Isavuconazole (BAL4815/8557) with six other antifungals against CNE isolates from patients with menigitis.
Methods: 180 CNE strains isolated from cerebrospinal fluid and blood were used. MICs were determined for amphotericin B (AMB), flucytocine (5FC), fluconazole (FLU), itraconazole (ITC), voriconazole (VOR), posaconazole (POS) and Isavuconazole (ISA). Microdilution testing was done in accordance with CLSI M27-A2 guidelines in RPMI 1640 MOPS broth with L-glutamine without bicarbonate. Plates were incubated at 35oC for 72 hours. The MIC was determined visually and spectrophotometrically as the lowest concentration of drug showing absence of growth or ≥ 50% reduction of growth compared with that of the growth control for AMB, and 5FC and azoles, respectively.
Results: No significant differences between visual and spectrophotometric reading was observed. Over all strains, MIC90s of AmB, 5FC, FLU, IT, VOR, POS, CAS and ISA were .5, 8, 8, .25, .25. .125, >64, and .125 mg/L, respectively.
Conclusions: Emergence of drug resistance to AmB, 5FC, FLC, and ITC for CNE as reported from other regions were not found. Overall, the activity of ISA was at least equal to FLU and equal to ITC, VOR and POS. ITC, VOR, POS, and ISA are the most active antifungal agents in vitro against CNE.