Differential activity of triazoles in two-drug combinations with the echinocandin caspofungin against Aspergillus fumigatus.
OBJECTIVE
We investigated the in vitro activity of various triazoles in two-drug combinations with the echinocandin caspofungin against clinical isolates of Aspergillus fumigatus.


METHODS
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.
Manavathu
Elias K
EK
Division of Infectious Diseases, Department of Medicine, Wayne State University, 427 Lande Building, 550 E. Canfield, Detroit, MI 48201, USA. aa1388@wayne.edu
Alangaden
George J
GJ
Chandrasekar
Pranatharthi H
PH
D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000254:growth & development; D000077336:Caspofungin; D004347:Drug Interactions / Q000502:physiology; D004359:Drug Therapy, Combination; D054714:Echinocandins; D006801:Humans; D055666:Lipopeptides; D008826:Microbial Sensitivity Tests / Q000379:methods; D010455:Peptides / Q000008:administration & dosage*; D010456:Peptides, Cyclic; D014230:Triazoles / Q000008:administration & dosage*
D054714:Echinocandins; D055666:Lipopeptides; D010455:Peptides; D010456:Peptides, Cyclic; D014230:Triazoles; D000077336:Caspofungin