In vitro susceptibility testing of Isavuconazole, posaconazole, voriconazole, fluconazole, flucytosine, and amphotericin B against Cryptococcus gattii and Cryptococcus neoformans.

Thompson, George R.; Fothergill Annette W.; Wickes, Brian; Patterson, Thomas F.


Introduction: Isavuconazole is a new triazole with proven in vitro activity against Aspergillus and Candida species. The activity of Isavuconazole against isolates of Cryptococcus neoformans (non-gattii Cryptococcus) and C. gattii has not yet been described.
Materials and
Methods: Isolates: Thirty-two isolates of C. neoformans (15 of serotype A, 3 of serotype AD, and 14 of serotype D), and forty-three isolates of C. gattii (8 of serotype C, and 35 of serotype B) were included. C. krusei ATCC (6258) and C. parapsilosis ATCC (22019) were used as quality controls. Antifungals: Isavuconazole (Basilea), fluconazole (Pfizer, Inc.), posaconazole (Shering-Plough), voriconazole (Pfizer), flucytosine (ICN Pharmaceuticals), and amphotericin B deoxycholate (Bristol Meyers Squibb) were used. Assays: The minimum inhibitory concentrations (MIC) were determined by the broth microdilution method in accordance with CLSI document M27-A2.
Results: All antifungals retained activity against the tested isolates. MIC 50 and 90, and geometric means are presented in table 1. A statistically significant difference favored lower MIC’s to flucytosine in C.gattii vs non-gattii Cryptococcus isolates. No other differences were seen between the susceptibilities of C.gattii compared to non-gattii isolates. No isolates with high-level resistance were detected.

Conclusions: These results confirm the potent in vitro activity of Isavuconazole against the most common Cryptococcus spp.. Newer azoles such as Isavuconazole, posaconazole, and voriconazole retained activity against isolates with higher fluconazole MICs (4 & 8) suggesting they may be an alternative treatment when similar isolates are encountered in clinical practice.



abstract No: 

    • Focus on Fungal Infection 18 (2008)