Antifungal Agents

Fungal infections represent an increasing threat to a growing number of immune- and medically compromised patients. Fungi, like humans, are eukaryotic organisms and there are a limited number of selective targets that can be exploited for antifungal drug development. This has also resulted in a very restricted number of antifungal drugs that are clinically available for the treatment of superficial and invasive fungal infections at the present time. Moreover, the utility of available antifungals is limited by toxicity, drug interactions and the emergence of resistance, which contribute to high morbidity and mortality rates. These limitations have created a demand for the development of new antifungals, particularly those with novel mechanisms of action. The 1990s can be considered the “golden era" of antifungal drug development with multiple big pharmaceutical companies actively engaged in the discovery and development of novel antifungals. However, this has largely become stagnant since then, and it has been two decades since the newest class of antifungal agents (the echinocandins) reached the market. Overall, there are currently few classes of FDA-approved antifungal agents clinically used in the treatment of fungal infections. In this chapter, we reviewed antifungal drugs and summarized their mechanisms of action, pharmacological profiles, and susceptibility to specific fungi. Approved antimycotics inhibit nucleic acid and microtubule synthesis, membrane ergosterol synthesis and cell wall polymers’ synthesis, or sequestrate ergosterol. The experimental antifungal drugs in clinical trials are also reviewed. We report sphingolipids and protein biosynthesis inhibitors, which represent the most promising emerging antifungal therapies.