title: Potentiation of antifungal activity of amphotericin B by azithromycin against Aspergillus species.
abstract: 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.
authors.affiliation: Department of Medicine, University of Florida College of Medicine, and VA Medical Center, Gainesville 32610, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Nguyen
authors.forename: C J
authors.initials: CJ
authors.lastname: Clancy
authors.forename: Y C
authors.initials: YC
authors.lastname: Yu
authors.forename: A S
authors.initials: AS
authors.lastname: Lewin
mesh_terms: 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
chemical_list: D000900:Anti-Bacterial Agents; D000666:Amphotericin B; D017963:Azithromycin