Postantifungal Effect of Antifungal Drugs against Candida: What Do We Know and How Can We Apply This Knowledge in the Clinical Setting?

Abstract

The study of the pharmacological properties of an antifungal agent integrates the drug pharmacokinetics, the fungal growth inhibition, the fungicidal effect and the postantifungal activity, laying the basis to guide optimal dosing regimen selection. The current manuscript reviews concepts regarding the postantifungal effect (PAFE) of the main classes of drugs used to treat Candida infections or candidiasis. The existence of PAFE and its magnitude are highly dependent on both the fungal species and the class of the antifungal agent. Therefore, the aim of this article was to compile the information described in the literature concerning the PAFE of polyenes, azoles and echinocandins against the Candida species of medical interest. In addition, the mechanisms involved in these phenomena, methods of study, and finally, the clinical applicability of these studies relating to the design of dosing regimens were reviewed and discussed. Additionally, different factors that could determine the variability in the PAFE were described. Most PAFE studies were conducted in vitro, and a scarcity of PAFE studies in animal models was observed. It can be stated that the echinocandins cause the most prolonged PAFE, followed by polyenes and azoles. In the case of the triazoles, it is worth noting the inconsistency found between in vitro and in vivo studies.

Keywords: 5-fluorocytosine; antifungal therapy; azoles; candidiasis; dosing regimen; echinocandins; polyenes; postantifungal effect.

Figure 1

Different factors that determine the variability in PAFE. TK: Time-kill; OD: Optical density.

Figure 2

Dose–antifungal response relation. PK and PD properties of antifungal drugs and main sources of variability.

Figure 3

The maximal concentration (C_max), the ratio of drug area under the concentration–time curve (AUC) to MIC (dotted line) over a 24 h period (AUC_0–24h/MIC) or the time (expressed as a percentage of the dosing interval) that drug concentrations are expected to exceed the MIC (%T > MIC) as PK/PD index that link the kinetics of antifungal disposition, MIC and PAFE values with the antifungal clinical efficacy.