Wiederhold NP, et al. - Researchers perform this work to address antifungal resistance. They identify antifungal resistance as a major clinical challenge to clinicians responsible for treating invasive fungal infections due to the limited arsenal of systemically available antifungal agents. Current drugs, in addition, seem limited by drug–drug interactions and serious adverse effects/toxicities that prevent their prolonged use or dosage escalation.

• Clinicians are particularly concerned regarding fluconazole resistance in non-Candida albicans species because of high incidence of infections caused by these species in different geographic locations worldwide and the elevated prevalence of resistance to this commonly used azole in many institutions.
• Researchers identified documentation of rising C. glabrata resistance to the echinocandins in several US institutions, and a higher percentage of these isolates may also be azole resistant.
• They also noticed worldwide incidence of azole resistance in Aspergillus fumigatus due to clinical and environmental exposure to this class of agents; these isolates can cause invasive infections with high mortality rates.
• In addition, there appear reduced susceptibility or pan-resistance to clinically available antifungals among several species of Aspergillus, and other molds, including Scedosporium and Fusarium species.
• They also recognize various investigational antifungals which are currently in preclinical or clinical development, including several of them that have the potential to overcome resistance observed against the azoles and the echinocandins.
• These investigational antifungals include agents that in addition target ergosterol and β-glucan biosynthesis, as well as compounds with novel mechanisms of action that may also overcome the limitations of currently available antifungal classes, including both resistance and adverse effects/toxicity.