Synergistic interaction of terbinafine with triazoles or amphotericin B against Aspergillus species

The in vitro activity of terbinafine alone and in combination with other an tifungal agents was tested against isolates of Aspergillus fumigatus, A. fl avus and A. niger. Testing was performed in a modified National Committee f or Clinical Laboratory Standards (NCCLS) macrodilution broth assay, and int eractions were examined using a checkerboard design. Terbinafine was highly active against Aspergillus isolates (minimum inhibitory concentration [MIC ] 0.01 to 2 mug ml(-1)) with a primary fungicidal action (minimum fungicida l concentration [MIC] 0.02 to 4 mug m(-1)). Amphotericin B was also highly active and cidal as expected (MIC 1 mug ml(-1), MFC 1 to 4 mug ml(-1)). The triazoles itraconazole and voriconazole were highly active but showed a va riable degree of cidal activity against the different strains, voriconazole having the more potent cidal activity. Fluconazole had no significant acti vity (MIC > 128 mug ml(-1)). Drug combinations were tested in the A. fumiga tus and A. niger strains. Terbinafine and amphotericin showed an additive t o synergistic interaction depending on the isolate. Combinations of terbina fine with itraconazole or voriconazole displayed a potent synergistic inter action and fungicidal activity against all isolates. Surprisingly, fluconaz ole also potentiated the activity of terbinafine in an additive to synergis tic fashion, despite its lack of activity alone. The results suggest potent ial clinical application of terbinafine in aspergillosis, either alone or i n combination with anmphotericin or triazoles.