Implications of Evolving and Emerging Pharmacokinetic-Pharmacodynamic Research for Triazoles and Echinocandins

AbstractPurpose of ReviewClinicians should be encouraged to use pharmacokinetic-pharmacodynamic (PK-PD) studies to optimize antifungal drug dosing in the absence of robust comparative effectiveness data or in cases where evidence of causality has not yet been firmly established. The purpose of this article is to review how new triazole and echinocandin PK-PD studies have contributed to our current understanding of antifungal selection and dose optimization against invasive fungal infections. Emerging infections such asC. auris and novel antifungal drugs such as rezafungin will also be highlighted. Future research endeavors are suggested where currently robust clinical outcomes data associated with PK-PD target attainment are lacking.Recent FindingsRecent results from clinical fluconazole PK-PD studies may indicate that unique AUC24/MIC thresholds exist for specificCandida species. The inability of recent studies to confirm previous fluconazole AUC24/MIC clinical PK-PD targets of 11 to 400 may also be due to previously unrecognized PK variability in special patient populations such as those with augmented renal clearance. A free AUC24/MIC threshold of 25 appears to be conserved across the azole antifungal class in animal models of invasive candidiasis. Current therapeutic drug monitoring guidance with voriconazole, posaconazole, and itraconazole has been used to indirectly confirm pre-clinical AUC24/MIC PK-PD targets in invasive candidiasis and aspergillosis. Elucidation of th...
Source: Current Fungal Infection Reports - Category: Infectious Diseases Source Type: research