Echinocandins

Fungal cells are wrapped in a wall built largely from a sugar polymer called 1,3-beta-D-glucan. Echinocandins block the enzyme complex that makes it, glucan synthase, so the wall cannot be properly built. Human cells have no cell wall and no glucan, which is why the drugs act selectively on fungi. Against Candida the effect is fungicidal in laboratory tests; against Aspergillus its activity is focused on the actively growing regions of the hyphae. Resistance arises mainly through mutations in the FKS genes that encode the enzyme's catalytic subunit, and these mutations can reduce susceptibility to the whole class. Rezafungin is a newer, longer-acting member.

Each drug reached approval through randomized human trials. In invasive candidiasis, caspofungin was at least as effective as amphotericin B (successful outcomes in 73% vs 62%) with significantly fewer drug-related adverse events¹. Anidulafungin was noninferior to fluconazole, with success at the end of intravenous therapy in 76% versus 60%². Rezafungin was compared with caspofungin in the ReSTORE trial of 199 patients with candidemia or invasive candidiasis: global cure at day 14 (59% vs 61%) and death or unknown survival status by day 30 (24% vs 21%) met the noninferiority margins³. Clinical failures due to resistant Candida or Aspergillus, some carrying FKS mutations, have been reported⁴.

The FDA approved caspofungin (Cancidas) in 2001, micafungin (Mycamine) in 2005, anidulafungin (Eraxis) in 2006 and rezafungin (Rezzayo) in 2023; approved uses include candidemia and other invasive Candida infections, esophageal candidiasis, Candida prevention in stem-cell transplant patients (micafungin), invasive aspergillosis when other therapy fails or is not tolerated and suspected infection in febrile neutropenia (caspofungin), with rezafungin limited to patients with few or no alternatives^4,5,6.

Labels across the class warn of hypersensitivity reactions including anaphylaxis, histamine-type infusion reactions such as rash, flushing and itching, and liver test abnormalities with rare hepatitis or liver failure. Micafungin adds warnings for hemolysis and kidney effects; caspofungin for severe skin reactions and liver enzyme rises with cyclosporine; rezafungin for photosensitivity^4,5,6. Common reactions include diarrhea, nausea, vomiting, fever and low potassium.

1. Mora-Duarte et al., N Engl J Med 2002PubMed
2. Reboli et al., N Engl J Med 2007PubMed
3. Thompson et al., Lancet 2023PubMed
4. FDA label: caspofungin acetateFDA label (DailyMed)
5. FDA label: micafunginFDA label (DailyMed)
6. FDA label: RezzayoFDA label (DailyMed)