Exploring exposure guided treatment optimisation of antifungal drugs in critically-ill patients with invasive candidiasis

Candida is a fungus which can penetrate the body into the bloodstream (invasive candidiasis) of severely-ill patients. This pathogen is the most prevalent fungus that is found in patients in the intensive care unit and is an important factor of prolonged hospital stay and high mortality among ICU patients. The correct antifungal agent and the correct dose of this antifungal drug are important for optimal treatment. The dose recommended in the patient leaflet for most antifungal agents is a standard dose and for every individual the same. This might be inappropriate, as specific patient characteristics may alter the drug concentration (pharmacokinetics), which could results in different drug concentrations in different patients. For example, differences in bodyweight, dialysis use and illness severity may lead to differences in blood concentrations. In this dissertation are the pharmacokinetics of fluconazole and micafungin (two antifungal agents) in ICU patients evaluated. The differences in pharmacokinetics for both agents in patients are significant and clinically relevant which may impact the treatment of invasive candidiasis. An individualized dose is necessery to guarantee the adequate amount of the drug in each individual to optimize treatment and potentially increase the success rate of the treatment. Individualized antifungal therapy based on the Candida species, patient characteristics and preferably the drug exposure is essential to optimize the treatment of invasive candidiasis.