Postantifungal effect and effects of sub-MIC concentrations on previously treated Candida sp. Influence of growth phase

Abstract

Objectives: This study evaluates the influence of growth phase on the postantifungal effect (PAFE) and on the effect of sub-MIC concentrations (1/4× MIC) on Candida sp. in PAFE stage (PAFSE). Methods: This stage was induced by pre-treatments of 1.5 h of C. albicans or C. glabrata in their exponential or stationary phase, with 1×, 4× or 8× MIC of four antifungal agents that are fundamental for modern candidiasis therapy. Results: 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 1/4× 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 1/4× 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. Conclusion: 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.