Potentiation of antifungal activity of amphotericin B by azithromycin against Aspergillus species

The potential role of azithromycin in combination with amphotericin B against 25 clinical isolates of Aspergillus was assessed, The MIC of amphotericin B was 1 mu g/ml for 44% of the isolates, 0.5 mu g/ml for 48%, and 0.25 mu gl/ml for 8%, All isolates were resistant to azithromycin. Synergism, defined as a greater than or equal to twofold reduction in the MIC of both drugs upon combination, was demonstrated between amphotericin B and azithromycin for all 25 isolates, To prove that azithromycin exerts its antifungal effect by inhibiting protein synthesis, we studied [S-35]-methionine incorporation into protein in one Aspergillus isolate. Neither amphotericin B at 0.125 mu g/ml (fourfold below its MIC) nor azithromycin at 16 mu g/ml (greater than or equal to 16-fold below its MIC) had any effect on protein synthesis when tested alone. Upon combination, however, a 68% inhibition in protein synthesis was evident by the inhibition of [S-35]-methionine incorporation.