Echinocandins

crop_square Key points

  • check_circle Semisynthetic intravenous antifungals most active against candida infections
  • check_circle Inhibit ergosterol biosynthesis by blocking the enzyme β-D-glucan synthase
  • check_circle Well-tolerated and safe drugs

crop_square Background and biochemistry

Echinocandins are a class of semisynthetic antifungal drugs. They were developed after the discovery of Echinocandin B, a metabolite with antifungal properties first isolated from Aspergillus fungi in 1974. It took several decades of research before caspofungin, derived from Glarea lozoyensis, became the first FDA-approved echinocandin in 2001 for treating invasive fungal infection. Two more agents of this class, micafungin (derived from Coleophoma empetri) and anidulafungin (derived from Aspergillus nidulans), were approved in the following years. All echinocandins in clinical use are cyclic amphiphilic hexapeptides. They possess an N-linked acyl fatty acid chain crucial for antifungal activity.

crop_square Mechanism of action

Echinocandins inhibit the biosynthesis of fungal cell walls. They bind to the enzyme complex (1 → 3)-β-D-glucan synthase which inhibits the synthesis of β-D-glucan. Echinocandins are fungicidal. However, the proportion of β-D-glucan in fungal cell walls varies significantly. Pathogenic fungi without relevant amounts of β-D-glucan in their cell walls (e.g., zygomycetes) are intrinsically resistant to echinocandins. Resistances against echinocandins have emerged in recent years. These are mostly mediated by mutations affecting the targeted enzyme complex making it less susceptible to echinocandins.

crop_square Drugs and spectrum of activity

  • Caspo­fungin
  • Mica­fungin
  • Anidula­fungin

Echinocandins are primarily used for treatment and prevention of invasive candida infections. Caspofungin may be used in invasive aspergillosis, however, echinocandin activity against Aspergillus spp. is variable. They show in vitro activity against other moulds like Histoplasma capsulatum but are currently not recommended for treatment in humans.

crop_square Pharmacokinetics

Echinocandins are solely available as intravenous formulations. They are highly protein-bound drugs. Elimination half-lives vary between 15h for Micafungin and 50h for anidulafungin. Tissue distribution is excellent, but all available agents penetrate the blood-brain barrier poorly. Echinocandins undergo hepatic metabolization and are primarily excreted via faeces.

crop_square Adverse drug effects

All agents of this class are generally well-tolerated and safe drugs. Adverse effects are usually mild and include gastrointestinal symptoms, headache, and electrolyte imbalance. Echinocandins rarely cause severe side effects such as liver failure and anaphylaxis.