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 microg/ml for 44% of the isolates, 0.5 microg/ml for 48%, and 0.25 microg/ml for 8%. All isolates were resistant to azithromycin. Synergism, defined as a > or = 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 in one Aspergillus isolate. Neither amphotericin B at 0.125 microg/ml (fourfold below its MIC) nor azithromycin at 16 microg/ml (> or = 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.
Nguyen
M H
MH
Department of Medicine, University of Florida College of Medicine, and VA Medical Center, Gainesville 32610, USA.
Clancy
C J
CJ
Yu
Y C
YC
Lewin
A S
AS
D000666:Amphotericin B / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001230:Aspergillus / Q000187:drug effects*; D017963:Azithromycin / Q000494:pharmacology*; D004357:Drug Synergism; D008826:Microbial Sensitivity Tests
D000900:Anti-Bacterial Agents; D000666:Amphotericin B; D017963:Azithromycin