Drug Interaction In Vitro between a Polyene (AmBisome; AmBi) and an Echinocandin (FK463;FK) vs. Aspergillus Species.



Current therapy vs. aspergillosis is poor, stimulating exploration of new agents and of combination therapy. Before clinical trials it is important to exclude antagonism between drugs to be used in combination. This study examined in broth macrodilution checkerboard testing the interaction between liposomal amphotericin (AmBi) and FK (Fujisawa) vs. 10 clinical Aspergillus isolates (4 fumigatus, 3 flavus, 2 terreus, 1 niger). MIC, MEC (min. effective conc., reduction of 4+ control growth to ≤2+), and MFC (minimum fungicidal concentration) were determined. AmBi results were 4 - >16, 2 - >8, 8 - >16 respectively, and FK >16, ≤0.06, >16. In combination, with 10/10 isolates there was no antagonism seen. All showed indifference (Fractional Inhibitory Concentration index = 2) and no potentiation for killing, but in 7/10 there was a trend toward synergy, i.e. partial inhibition when both drugs present was greater than partial inhibition by each alone, though definition of synergy (requiring clear tube) not achieved. In summary these 2 drugs do not antagonize each other against this difficult fungus to inhibit, and there is some evidence of improvement of activity.

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39th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 39th