Enhancement of the in vitro activity of amphotericin B against Aspergillus spp. by tetracycline analogs

Strains of Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger were tested for in vitro susceptibility to amphotericin B alone and in combination with fixed concentrations of tetracycline, doxycycline, or minocycline, using buffered minimal essential medium in microtiter plates. Enhanced inhibitory activity was seen, especially with combinations of amphotericin B and minocycline. Synergistic activity between amphotericin B and minocycline was observed in each of five isolates of each species when tested in a checkerboard dilution scheme. Time-kill curves demonstrated killing an A. fumigatus isolated at concentrations of amphotericin B that were four- or eightfold lower in the presence of 5 or 15 micrograms of minocycline per ml than with amphotericin B alone. Of the tetracycline analogs tested, minocycline has the greatest activity against A. fumigatus, A. flavus, and A. niger conidia when potentiated by amphotericin B.