Echinocandin

An echinocandin is a class of antifungal drugs that inhibit the fungal enzyme 1,3-beta-D-glucan synthase, thereby blocking synthesis of beta-1,3-glucan in the cell wall. This weakens the cell wall and leads to cell death in susceptible fungi. The principal agents are caspofungin, micafungin, and anidulafungin. Echinocandins are fungicidal against most Candida species and generally fungistatic against Aspergillus species; their activity against Cryptococcus and many dimorphic or endemic fungi is limited. They are not active against Pneumocystis jirovecii.

Clinical use includes treatment of invasive candidiasis and candidemia in many settings, especially when rapid activity against Candida is needed or azoles are unsuitable. They are also used for esophageal candidiasis and as salvage or step-down therapy when other antifungals are undesirable. Invasive aspergillosis is typically managed with other agents, with echinocandins used as adjunct or salvage therapy in some cases.

Pharmacology and safety: Echinocandins are administered by intravenous infusion and have poor oral bioavailability. They generally have favorable safety profiles with minimal nephrotoxicity; infusion-related reactions and transient hepatic enzyme elevations can occur. They are largely hepatically metabolized with limited drug interactions, and central nervous system penetration is limited.

Resistance and limitations: Resistance can arise from mutations in FKS genes encoding beta-1,3-glucan synthase, with higher occurrence in Candida glabrata. Cross-resistance among echinocandins is possible but not universal. They do not cover Pneumocystis jirovecii and show limited activity against many molds beyond certain Candida species.

History: The first echinocandin, caspofungin, was approved in 2001, followed by micafungin in 2005 and anidulafungin in 2006.