Antifungals: mechanism of action and resistance, established and novel drugs

Serious fungal infections, caused mostly by opportunistic species, are increasingly common in immunocompromised and other vulnerable patients. The use of antifungal drugs, primarily azoles and polyenes, has increased in parallel. Yet, established agents do not satisfy the medical need completely: azoles are fungistatic and vulnerable to resistance, whereas polyenes cause serious host toxicity. Drugs in clinical development include echinocandins, pneumocandins, and improved azoles. Promising novel agents in preclinical development include several inhibitors of fungal protein, lipid and cell wall syntheses. Recent advances in fungal genomics, combinatorial chemistry, and high-throughput screening may accelerate the antifungal discovery process.