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Effects of antifungal agent combinations administered simultaneously and sequentially against Aspergillus fumigatus

The in vitro effects of antifungal agent combinations administered simultaneously and sequentially against 15 strains of Aspergillus fumigatus were tested by the yeast-malt broth method. The synergistic effect of the combination of amphotericin B (AMPH) and miconazole was observed in nine strains (60%). However, the combinations of AMPH and fluconazole, AMPH and ketoconazole, and AMPH and itraconazole administered simultaneously showed antagonistic effects against three (20%), five (34%), and four (26%) strains, respectively. The effects of combinations of azole antifungal agents administered simultaneously were indifferent or antagonistic against A. fumigatus. In experiments measuring the effects of sequentially administered antifungal agents, however, pretreatment with AMPH and then azole antifungal agents exhibited better in vitro efficacy than that found in experiments measuring the effects of simultaneously administered AMPH and azole compounds.