Differential activity of triazoles in two-drug combinations with the echinocandin caspofungin against Aspergillus fumigatus

Objectives: We investigated the in vitro activity of various triazoles in two-drug combinations with the echinocandin caspofungin against clinical isolates of Aspergillus fumigatus. Method: Conidial suspensions were prepared from 20 clinical isolates of A. fumigatus highly susceptible to itraconazole, voriconazole, posaconazole and ravuconazole (MIC-0 range 0.125-1 mg/L), and caspofungin (MIC-0 range 32-64 mg/L). The in vitro susceptibility of A. fumigatus to two-drug combinations of itraconazole, voriconazole, posaconazole and ravuconazole with caspofungin was evaluated by the fractional inhibitory concentration index (FICI) method. Results: Two-drug combinations of caspofungin with itraconazole (FICI = 0.49 +/- 0.04) or posaconazole (FICI = 0.32 +/- 0.09) provided synergic interaction. On the other hand, ravuconazole (FICI = 0.61 +/- 0.31) and voriconazole (FICI = 1.61 +/- 0.42) in combination with caspofungin showed no interaction against A. fumigatus. Conclusions: Our data show that the in vitro antifungal efficacies of combinations of members from two different classes are not always similar and hence are not predictable.