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 patient s. The use of antifungal drugs, primarily azoles and polyenes, has inc reased 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 devel opment include echinocandins, pneumocandins, and improved azoles. Prom ising novel agents in preclinical development include several inhibito rs of fungal protein, lipid and cell wall syntheses. Recent advances i n fungal genomics, combinatorial chemistry, and high-throughput screen ing may accelerate the antifungal discovery process.