Antagonistic interactions between azoles and amphotericin B with yeasts depend on azole lipophilia for special test conditions in vitro
- 1 August 1995
- journal article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 39 (8), 1779-1783
- https://doi.org/10.1128/aac.39.8.1779
Abstract
The interactions of the azole antifungal agents fluconazole, itraconazole, ketoconazole, or miconazole with amphotericin B (AmB) in their effect on Candida albicans were investigated. These four azoles antagonized the fungistatic activity of AmB at sub-MICs if both substances acted simultaneously. This coincubation test was primarily developed to observe the azole-mediated demethylase inhibition quantitatively by bioassay. Interestingly, the occurrence of azole-AmB antagonism depended on azole lipophilia if specially selected test conditions were applied. By a consecutive incubation regimen, preincubation at high azole concentrations (1 to 50 micrograms/ml) and then subsequent incubation with AmB (1 microgram/ml), only preincubation with the three lipophilic azoles decreased the fungicidal activity of AmB but not that of FCZ. It was shown that yeasts absorb only lipophilic azoles to a remarkable extent. This fact might be responsible for the absence of antagonism of FCZ to AmB when yeasts were incubated consecutively. It can be concluded with caution that consecutive treatment of candidiasis with FCZ and AmB does not necessarily result in a clinically relevant antagonism.Keywords
This publication has 16 references indexed in Scilit:
- Fluconazole resistance in Candida glabrataAntimicrobial Agents and Chemotherapy, 1993
- Interactions of amphotericin B and SCH 39304 in the treatment of experimental murine candidiasis: lack of antagonism of a polyene-azole combinationAntimicrobial Agents and Chemotherapy, 1991
- Interactions in vitro between polyenes and imidazoles against yeastsJournal of Antimicrobial Chemotherapy, 1991
- Combination therapy for systemic mycosisInfection, 1989
- The Effect of Ketoconazole on Amphotericin B in a Model of Disseminated AspergillosisThe Journal of Infectious Diseases, 1985
- Effect of ketoconazole on the fungicidal action of amphotericin B in Candida albicansAntimicrobial Agents and Chemotherapy, 1983
- Interactions among amphotericin B, 5-fluorocytosine, ketoconazole, and miconazole against pathogenic fungi in vitroAntimicrobial Agents and Chemotherapy, 1982
- Antifungal Action of Amphotericin B in Combination with Other Polyene or Imidazole AntibioticsThe Journal of Infectious Diseases, 1982
- In vitro synergy and antagonism of antifungal agents against yeast-like fungiPublished by Oxford University Press (OUP) ,1979
- Inhibition of Potentially Pathogenic Yeastlike Fungi by Clotrimazole in Combination with 5-Fluorocytosine or Amphotericin BAntimicrobial Agents and Chemotherapy, 1976