Interactions in vitro between polyenes and imidazoles against yeasts

Abstract

The polyenes, amphotericin B and mepartricin and the imidazoles, miconazole, ketoconazole, itraconazole and fluconazole, were studied either alone or in paired polyene-imidazole combinations to determine their activity in vitro against clinical yeast isolates. The methods included shaken and standing liquid cultures, continuous cultures and chequerboard titrations, with or without the incorporation of pooled human plasma. The polyenes were found to exert an immediate cidal action even with high cell populations whereas the imidazoles demonstrated a time-dependent fungistatic activity which increased very slowly with increase in drug concentration. The interactions observed with the paired combinations were consistent and were found to be anomalous with all methods used. The activity of the imidazoles was enhanced by the presence of the polyenes; by contrast the polyenes were strongly antagonized by the imidazoles.