In Vitro Activity of Isavuconazole (BAL4815) Compared with Seven other Antifungal Agents against 309 Prospectively Collected Clinical Candida Isolates from The Netherlands



Background: Isavuconazole (ISA;BAL 4815/8557) is an antifungal drug of a new generation of triazoles including posaconazole, voriconazole and ravuconazole. We compared the in vitro activity of ISA against Candida species isolated from invasive infections with seven other antifungal drugs.
Methods: 309 strains were prospectively isolated during a 6-month period (07- 2005 – 01-2006). MICs were determined for amphotericin B (AmB), flucytocine (5FC), fluconazole (FLU), itraconazole (ITC), voriconazole (VOR), posaconazole (POS), caspofungin (CAS) and ISA. Microdilution testing was done in accordance with CLSI M27-A2 in RPMI 1640 MOPS broth with L-glutamine without bicarbonate and incubated at 35oC for 24 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: Species distribution was C. albicans (61%), C. glabrata (21%), C. tropicalis (5%) and C. parapsilosis (4%). Only 1% of C. albicans was resistant to FLU compared to 10% of the non albicans Candida species isolates. Among the FLU susceptible (MIC≤ 8) non albicans Candida species isolates (n=103) the MIC90 and MIC range for ISA, CAS, FLU,ITC, POS, VOR, 5FC and AmB was 0.016, <0.002-0.125; 0.5, 0.016-2; 4, 0.125-4; 0. 25, <0.016-0.5; 0.125, <0.016- 0.25; 0.125, <0.016-0.25; 0.063, <0.063->64; 0.5, 0.063-1 mg/L respectively. Among the FLU less susceptible (MIC ≥16) non-albicans isolates (n=10) the MIC90 and MIC range for ISA, CAS, FLU, ITC,POS, VOR, 5FC and AmB was 0.125, 0.004-0.125; 0.5, 0.016-0.5; 64, 16-64; 0.5, 0.031-0.5; 0.5, 0.031-0.5; 1, 0.125-1;4, <0.063-8;1, 0.125-1 mg/L respectively. Among the FLU susceptible (MIC≤ 8) C. albicans isolates (n=196) the MIC90 and MIC range for ISA, CAS, FLU, ITC, POS, VOR, 5FC and AmB was <0.002, <0.002-0.063; 1, 0.016-2; 0.25, <0.063-8; 0.063, <0.016-0.5; <0.016, <0.016-0.5; <0.016, <0.016-0.125; 0.063, <0.063-2; 1, 0.125-2 mg/L respectively.
Conclusion: Isavuconazole has a high in vitro activity against invasive Candida isolates with lower MICs than the seven comparator drugs. Isavuconazole is a potential attractive new agent to treat invasive Candida infections.


abstract No: 

    • ECCMID 17th (2007)