Influence of temperature and concentration on the postantifungal effect and the effects of sub-MIC concentrations of four antifungal agents on previously treated Candida species

Abstract

Background: The objective of this study was to investigate the impact of different temperatures (22, 35 and 37°C) on the postantifungal effect (PAFE) and the effect of sub-MIC concentrations (1/4 × MIC) on Candida albicans and Candida glabrata in PAFE stage (PAFSE). Methods: This stage was induced by a 1.5-hour pretreatment with different doses (1 ×, 4 × and 8 × MIC) of four antifungal agents that are fundamental to modern candidiasis therapy. Results: The temperature, as well as the dose of the antifungal agent that was applied during the pretreatment, determined the duration of the two studied effects. An increase in the temperature and/or the dose prolonged the duration of the PAFE and PAFSE in both species, independent of the applied antifungal agent. Amphotericin B and 5-fluorocytosine always induced significant PAFEs (0.5–4.8 h and 0.5–3.0 h, respectively), which were increased (0.7–3.4 h and 0.5–3.2 h, respectively) by posterior exposure to 1/4 × MIC of the respective antifungal agent. In the case of ketoconazole and fluconazole, temperature and concentration were especially important. Although neither antimycotics was able to induce a significant PAFE, posterior exposure to 1/4 × MIC of each of the two azoles led in both yeast species to a significant PAFSE of up to 0.8 h (if the concentrations and/or the temperatures were high enough). Conclusion: Factors such as temperature and concentration could be important when choosing an antifungal agent.