Assessment of efficacy of antifungals in experimental models of invasive aspergillosis in an era of emerging resistance: the value of real-time quantitative PCR

Experimental models of invasive aspergillosis (IA) have been used to explore pharmacokinetic and pharmacodynamic (PK/PD) properties of antifungal agents. Survival is still considered the golden standard effect measure but has the disadvantage that a large number of animals are needed to determine the dose–response relationships and PK/PD of antifungals. The feasibility of using fungal load by real-time quantitative PCR (qPCR) as an effect measure has been explored recently. The majority of studies reported convincingly demonstrate a larger dynamic range for qPCR compared to conventional assays. However interpretation and translating the results to guidance in clinical decision making need further study. It is expected that the use of qPCR will become the primary outcome measure for assessment of PK/PD relationships of antifungals in experimental models of IA.

► Azole resistance has emerged in Aspergillus fumigatus. ► Survival studies indicate clear exposure–response relationships for azoles and A. fumigatus. ► Extensive PK/PD relationships of antifungals are highly needed for the evaluation of dosing regimens towards susceptible and resistant fungi. ► qPCR is a promising method to evaluate antifungal efficacy in invasive aspergillosis.