Pharmacokinetics of antifungal drugs in severely ill patients

Continued efforts are required to improve the currently daunting perspective of patients with invasive fungal infections. Even with the introduction of new antifungal agents morbidity and mortality of invasive fungal infections have remained high and the numbers of patients at risk for invasive fungal infections are increasing. The current antifungal treatment can be improved by expanding the knowledge of the pharmacokinetics of antifungal agents in specific patient populations and to provide reliable therapeutic drug monitoring services.
The exposure to anidulafungin was investigated in intensive care patients. Anidulafungin exposure was low in our critically ill patients. Concerns about a low anidulafungin exposure seemed unnecessary because of the good susceptibility of the isolated strains for anidulafungin. Since obtaining a full concentration-time curve to determine the exposure is not always feasible or appropriate a limited sampling strategy was developed. Anidulafungin exposure can be adequately estimated with the concentration from a single sample.
Although routine therapeutic drug monitoring of voriconazole appears to be beneficial no data are available on the implementation of voriconazole therapeutic drug monitoring in daily practice. Even though voriconazole concentrations were measured in most patients we concluded that the performance of voriconazole therapeutic drug monitoring can still be improved to overcome problems encountered. To be able to explain more of the observed variability in voriconazole concentrations, we investigated whether inflammation might influence voriconazole trough concentrations. Inflammation is associated with voriconazole trough concentrations. This knowledge can be helpful in therapeutic drug monitoring of voriconazole to maintain concentrations in the therapeutic window.