Potentiation of antifungal activity of amphotericin B by azithromycin againstAspergillus species

The potential role of azithromycin in combination with amphotericin B against 25 clinical isolates ofAspergillus was assessed. The MIC of amphotericin B was 1 μg/ml for 44% of the isolates, 0.5 μg/ml for 48%, and 0.25 μg/ml for 8%. All isolates were resistant to azithromycin. Synergism, defined as a ≥ 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 [35S]-methionine incorporation into protein inone Aspergillus isolate. Neither amphotericin B at 0.125 μg/ml (fourfold below its MIC) nor azithromycin at 16 μg/ml (≥ 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 [35S]-methionine incorporation.