Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1995 Aug;39(8):1779–1783. doi: 10.1128/aac.39.8.1779

Antagonistic interactions between azoles and amphotericin B with yeasts depend on azole lipophilia for special test conditions in vitro.

M Scheven 1, F Schwegler 1
PMCID: PMC162825  PMID: 7486918

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.

Full Text

The Full Text of this article is available as a PDF (260.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beggs W. H., Sarosi G. A., Steele N. M. Inhibition of potentially pathogenic yeastlike fungi by clotrimazole in combination with 5-fluorocytosine or amphotericin B. Antimicrob Agents Chemother. 1976 Jun;9(6):863–865. doi: 10.1128/aac.9.6.863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brajtburg J., Kobayashi D., Medoff G., Kobayashi G. S. Antifungal action of amphotericin B in combination with other polyene or imidazole antibiotics. J Infect Dis. 1982 Aug;146(2):138–146. doi: 10.1093/infdis/146.2.138. [DOI] [PubMed] [Google Scholar]
  3. Chandrasekar P. H., Gatny C. M. Effect of fluconazole prophylaxis on fever and use of amphotericin in neutropenic cancer patients. Bone Marrow Transplantation Team. Chemotherapy. 1994 Mar-Apr;40(2):136–143. doi: 10.1159/000239184. [DOI] [PubMed] [Google Scholar]
  4. Cosgrove R. F., Beezer A. E., Miles R. J. In vitro studies of amphotericin B in combination with the imidazole antifungal compounds clotrimazole and miconazole. J Infect Dis. 1978 Nov;138(5):681–685. [PubMed] [Google Scholar]
  5. Dupont B., Drouhet E. In vitro synergy and antagonism of antifungal agents against yeast-like fungi. Postgrad Med J. 1979 Sep;55(647):683–686. doi: 10.1136/pgmj.55.647.683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hitchcock C. A., Pye G. W., Troke P. F., Johnson E. M., Warnock D. W. Fluconazole resistance in Candida glabrata. Antimicrob Agents Chemother. 1993 Sep;37(9):1962–1965. doi: 10.1128/aac.37.9.1962. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Mikami Y., Scalarone G. M., Kurita N., Yazawa K., Uno J., Miyaji M. Synergistic postantifungal effect of flucytosine and fluconazole on Candida albicans. J Med Vet Mycol. 1992;30(3):197–206. doi: 10.1080/02681219280000261. [DOI] [PubMed] [Google Scholar]
  8. Odds F. C. Interactions among amphotericin B, 5-fluorocytosine, ketoconazole, and miconazole against pathogenic fungi in vitro. Antimicrob Agents Chemother. 1982 Nov;22(5):763–770. doi: 10.1128/aac.22.5.763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Petrou M. A., Rogers T. R. Interactions in vitro between polyenes and imidazoles against yeasts. J Antimicrob Chemother. 1991 Apr;27(4):491–506. doi: 10.1093/jac/27.4.491. [DOI] [PubMed] [Google Scholar]
  10. Polak A. Combination therapy for systemic mycosis. Infection. 1989 Jul-Aug;17(4):203–209. doi: 10.1007/BF01639520. [DOI] [PubMed] [Google Scholar]
  11. Ryder N. S. Biochemical mode of action and enantiomeric selectivity of SDZ 89-485, a new triazole antimycotic. J Med Vet Mycol. 1990;28(5):385–394. doi: 10.1080/02681219080000491. [DOI] [PubMed] [Google Scholar]
  12. Ryley J. F., Wilson R. G., Barrett-Bee K. J. Azole resistance in Candida albicans. Sabouraudia. 1984;22(1):53–63. [PubMed] [Google Scholar]
  13. Schaffner A., Frick P. G. The effect of ketoconazole on amphotericin B in a model of disseminated aspergillosis. J Infect Dis. 1985 May;151(5):902–910. doi: 10.1093/infdis/151.5.902. [DOI] [PubMed] [Google Scholar]
  14. Sud I. J., Feingold D. S. Effect of ketoconazole on the fungicidal action of amphotericin B in Candida albicans. Antimicrob Agents Chemother. 1983 Jan;23(1):185–187. doi: 10.1128/aac.23.1.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Sugar A. M. Interactions of amphotericin B and SCH 39304 in the treatment of experimental murine candidiasis: lack of antagonism of a polyene-azole combination. Antimicrob Agents Chemother. 1991 Aug;35(8):1669–1671. doi: 10.1128/aac.35.8.1669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Vanden Bossche H. Biochemical targets for antifungal azole derivatives: hypothesis on the mode of action. Curr Top Med Mycol. 1985;1:313–351. doi: 10.1007/978-1-4613-9547-8_12. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES