Antagonistic effects of fluconazole and 5-fluorocytosine on candidacidal action of amphotericin B in human serum.
This study addressed the effects of fluconazole and 5-fluorocytosine on the candidacidal activity of amphotericin B in the presence of human serum. A Candida albicans isolate that was susceptible to all three agents according to standard testing procedures was employed. Fungicidal activity was estimated by using a flow cytometric procedure that exploited the fact that yeast cells killed by amphotericin B diminish in size and take up propidium iodide. The following findings were made. (i) Fluconazole and 5-fluorocytosine each failed to inhibit pseudohyphal formation and cell aggregation even when applied at 10 and 50 micrograms/ml, respectively, for up to 10 h. Hence, these agents were not fungistatic when tested in the presence of serum. (ii) Simultaneous application of 5-fluorocytosine had neither enhancing nor inhibitory effects on the fungicidal activity of amphotericin B. However, yeasts that were preincubated for 20 h with 5-fluorocytosine became less susceptible to killing by amphotericin B. (iii) Fluconazole exerted a frank antagonistic effect on the fungicidal activity of amphotericin B. Thus, under our in vitro conditions, both fluconazole and 5-fluorocytosine can overtly antagonize the candidacidal action of amphotericin B.
Martin
E
E
Institute of Medical Microbiology, University of Mainz, Germany.
Maier
F
F
Bhakdi
S
S
D000666:Amphotericin B / Q000037:antagonists & inhibitors*; D001790:Blood Physiological Phenomena; D002176:Candida albicans / Q000187:drug effects*; D005434:Flow Cytometry; D015725:Fluconazole / Q000494:pharmacology*; D005437:Flucytosine / Q000494:pharmacology*; D006801:Humans
D000666:Amphotericin B; D015725:Fluconazole; D005437:Flucytosine