Activity of fluconazole: postantifungal effect, effects of low concentrations and of pretreatment on the susceptibility of Candida albicans to leucocytes

Exposure times and serum concentrations in humans after treatment with multiple doses of fluconazole have been studied to measure: (a) the postantifungal effect (PAFE) on Candida albicans, at two concentrations of the drug in the presence or absence of 10% human serum; (b) the activity of low concen...

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Bibliographic Details
Published in:	Journal of antimicrobial chemotherapy Vol. 34; no. 1; p. 93
Main Authors:	Minguez, F, Chiu, M L, Lima, J E, Nique, R, Prieto, J
Format:	Journal Article
Language:	English
Published:	England 01-07-1994
Subjects:	Blood Physiological Phenomena Candida albicans - drug effects Fluconazole - pharmacology Humans Kinetics Leukocytes - drug effects Leukocytes - physiology Time Factors
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Summary:	Exposure times and serum concentrations in humans after treatment with multiple doses of fluconazole have been studied to measure: (a) the postantifungal effect (PAFE) on Candida albicans, at two concentrations of the drug in the presence or absence of 10% human serum; (b) the activity of low concentrations of the drug on yeasts previously exposed to fluconazole with or without 10% human serum; and (c) the effect of fluconazole pretreatment on the fungicidal activity of leucocytes and serum against C. albicans. Fluconazole showed no PAFE against C. albicans between -0.1 and -0.7 h, but when the assays were performed in the presence of serum, concentration dependent PAFEs were obtained (1.1 h-3.6 h). Pretreated yeasts were more susceptible than untreated yeasts to low concentrations of the drug. The decrease in growth was dependent on the concentration used in pretreatment. Growth delay was also more marked when the yeast cells were tested in the presence of serum. Pretreatment of the growing C. albicans cells with fluconazole increased their vulnerability to killing by leucocytes mainly in the first hour (P < 0.05). These results could partially explain why fluconazole has more activity in vivo than in vitro.
ISSN:	0305-7453
DOI:	10.1093/jac/34.1.93