ANTAGONISTIC INTERACTIONS BETWEEN AZOLES AND AMPHOTERICIN-B WITH YEAST DEPEND ON AZOLE LIPOPHILIA FOR SPECIAL TEST CONDITIONS IN-VITRO

The interactions of the azole antifungal agents fluconazole, itraconaz ole, ketoconazole, or miconazole with amphotericin B (AmB) in their ef fect on Candida albicans were investigated, These four azoles antagoni zed the fungistatic activity of AmB at sub-MICs if both substances act ed simultaneously, This coincubation test was primarily developed to o bserve the azole-mediated demethylase inhibition quantitatively by bio assay. Interestingly, the occurrence of azole-AmB antagonism depended on azole lipophilia if specially selected test conditions were applied . By a consecutive incubation regimen, preincubation at high azole con centrations (1 to 50 mu g/ml) and then subsequent incubation with AmB (1 mu g/ml), only preincubation with the three lipophilic azoles decre ased the fungicidal activity of AmB but not that of FCZ. It was shown that yeasts absorb only lipophilic azoles to a remarkable extent. This fact might be responsible for the absence of antagonism of FCZ to AmB when yeasts were incubated consecutively. It can be concluded with ca ution that consecutive treatment of candidiasis with FCZ and AmB does not necessarily result in a clinically relevant antagonism.