Post-antifungal effect and effects of sub-MIC concentrations on previously treated Candida spp.: influence of exposure time and concentration.
This study evaluates the influence of exposure time and concentration on the post-antifungal effect (PAFE) and the effect of sub-MIC concentrations (1/4 x MIC) on Candida albicans and C. glabrata in the PAFE stage (PAFSE). This stage was induced by pretreatment for 1.5, 3 or 12 h with 1 x, 4 x or 8 x MIC of 4 antifungal agents fundamental to modern candidiasis therapy. The length of the 2 effects studied was dependent on the concentration of the antifungal agent applied during pretreatment, as well as on the exposure time. An increase in the dose and/or longer pretreatment prolonged the duration of the PAFE and PAFSE in both species and with all the antifungal agents. Significant PAFEs were always observed for amphotericin B and 5-fluorocytosine (0.8-13 h and 0.6-10.8 h, respectively). These values were increased (by 2.3-8.7 h and 1.5-7.8 h, respectively) by posterior exposure to 1/4 x MIC of the respective antifungal agent. Neither ketoconazole nor fluconazole were able to induce significant PAFEs, even with exposures of up to 12 h duration and a dose of 8 x MIC. However, treatment with 1/4 x MIC of each of the 2 azoles led to significant PAFSEs in both yeast species, of up to 6.5 h duration with ketoconazole and 1.7 h with fluconazole, if the concentrations and/or exposure times were sufficiently high.
García
M T
MT
Department of Microbiology, School of Medicine, Universidad Complutense, Madrid, Spain.
Llorente
M T
MT
Mínguez
F
F
Prieto
J
J
D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects*; D041221:Candida glabrata / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D025141:Drug Resistance, Fungal; D015725:Fluconazole / Q000494:pharmacology; D007654:Ketoconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D013997:Time Factors
D000935:Antifungal Agents; D000666:Amphotericin B; D015725:Fluconazole; D007654:Ketoconazole