Beyond tissue concentrations: antifungal penetration at the site of infection

Abstract

Despite advances in antifungal therapy, invasive fungal infections remain a significant cause of morbidity and mortality worldwide. One important factor contributing to the relative ineffectiveness of existing antifungal drugs is insufficient drug exposure at the site of infection. Despite the importance of this aspect of antifungal therapy, we generally lack a full appreciation of how antifungal drugs distribute, penetrate, and interact with their target organisms in different tissue subcompartments. A better understanding of drug distribution will be critical to guide appropriate use of currently available antifungal drugs, as well as to aid development of new agents. Herein we briefly review current perspectives of antifungal drug exposure at the site of infection and describe a new technique, matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging, which has the potential to greatly expand our understanding of drug penetration.

Keywords: MALDI imaging; antifungals; drug quantification; posaconazole; site of infection; tissue penetration.