Postantifungal Effect and Effects of Sub-MIC Concentrations on Previously Treated Candida sp. Influence of Growth Phase

Abstract

This study evaluates the influence of growth phase on the postantifungal effect (PAFE) and on the effect of sub-MIC concentrations (1/4x MIC) on Candida sp. in PAFE stage (PAFSE). This stage was induced by pre-treatments of 1.5 h of C. albicans or C. glabrata in their exponential or stationary phase, with 1x, 4x or 8x MIC of four antifungal agents that are fundamental for modern candidiasis therapy. Ketoconazole and fluconazole induced longer PAFSEs on microorganisms in logarithmic growth phase. However, this influence did not exist in the case of PAFSEs induced by AmB and 5-Fc or with the postantifungal effect induced by the four antifungal agents. In any way, significant PAFEs were always observed for Amphotericin B and 5-fluorocytosine (0.8-4.8 and 0.5-3 h, respectively, depending on the treatment dose). These values were increased (2.3-3.6 and 1.4-3.2 h respectively, depending on the pre-treatment dose) by posterior exposition to 1/4x MIC of the respective antifungal agent. In the case of ketoconazole and fluconazole, both antimycotics were not able to induce significant PAFEs, but posterior treatments to 1/4x MIC of each of the two azoles led in both yeast species to significant PAFSE of up to 2.6 h duration with ketoconazole, and 0.8 h with fluconazole, depending on the pre-treatment concentration. The growth phase of microorganisms should be considered in the planning of dosage protocols with azoles, because if the concentration applied is not high enough, the sub-MIC effects could be no significant for fungi in stationary phase of large wounds. Amphotericin B and 5-fluorocytosine induced significant postantifungal effect onCandida sp. This effect was increased by posterior exposition to sub-MIC concentration of the antifungal agents. Ketoconazole and fuconazole were not able to induce significant PAFEs at the concentrations tested, but posterior treatments to sub-MIC concentrations led to significant PAFSE. The growth phase of the culture at the time of its pre-treatment did not influence the length of the PAFE induced in it. However, the effect of the sub-MIC concentrations of Kz or Flu in yeast in PAFE phase was greater on yeast in exponential phase than for cultures in stationary phase.