Importance of pharmacokinetic considerations for selecting therapy in the treatment of invasive fungal infections.

Invasive fungal infections continue to be a significant cause of morbidity and mortality among at-risk patients. Over the last decade, the epidemiology of invasive mycoses has been defined by increasing rates of infection caused by azole-resistant yeast (Candida glabrata, Candida krusei), Aspergillus, and in some centers, non-Aspergillus moulds, such as Fusarium species, Scedosporium species, and Mucorales. Early and appropriate antifungal therapy is crucial for a favorable clinical outcome. When selecting antifungal therapy--especially during the initial acute phases of treatment--spectrum of activity and pharmacokinetic characteristics are key treatment considerations. Important pharmacokinetic considerations for selecting antifungal therapy in the treatment of invasive fungal infections include drug-drug interactions and variability in adsorption that may limit efficacy during the early phase of treatment, poor oral availability, and variable tissue distribution. A patient's underlying condition and pharmacogenetics also may affect the pharmacokinetics of antifungal drugs, resulting in interpatient pharmacokinetic differences.