Antifungal

Antifungal agents are medicines used to treat fungal infections. They are used topically for skin and mucosal infections and systemically for invasive disease, particularly in people with weakened immune systems. Fungi contain ergosterol in their membranes and beta-glucans in their cell walls, features that many antifungals specifically exploit to inhibit growth or cause death.

Major classes include polyenes (for example amphotericin B and nystatin), azoles (fluconazole, itraconazole, voriconazole, posaconazole), echinocandins (caspofungin, micafungin, anidulafungin), and allylamines (terbinafine). Polyenes bind ergosterol to form membrane pores. Azoles inhibit lanosterol 14-demethylase, reducing ergosterol synthesis. Echinocandins block beta-1,3-glucan synthesis, weakening the fungal cell wall. Allylamines inhibit squalene epoxidase, decreasing ergosterol production. Flucytosine, a pyrimidine analog, disrupts fungal DNA and RNA when taken up by the organism, and is usually used with other agents for specific infections.

Clinical use varies by organism and site. Topical antifungals treat dermatophyte and candidal skin and nail infections; systemic agents are used for candidemia, cryptococcal meningitis, invasive aspergillosis, and other systemic mycoses. Resistance can arise through target modification, efflux, or biofilm formation, and combination therapy is sometimes employed to improve efficacy or prevent resistance.

Safety and monitoring considerations include nephrotoxicity and infusion reactions with amphotericin B; hepatotoxicity and drug interactions with many azoles; insulin elevation or QT effects with certain azoles; liver enzyme monitoring for many agents; and hematologic toxicity with flucytosine. Dosing, duration, and drug selection depend on organism, site of infection, prior therapy, and patient factors.