Mechanism of Action and Target
Echinocandins target the fungal cell wall, which is composed of chitin, glycoproteins, and glucans. These drugs non-competitively inhibit the enzyme β-(1,3)-D-glucan synthase.
- Blocks the incorporation of glucose into the growing polysaccharide chain.
- Disrupts β-(1,3)-D-glucan synthesis, leading to loss of cell wall integrity.
- Causes osmotic stress, resulting in osmotic lysis and fungal cell death.
These drugs are safe for humans because mammalian cells lack a cell wall and do not possess this enzymatic target.
Classification and Spectrum of Activity
The class includes three main agents: caspofungin, micafungin, and anidulafungin. Their antimicrobial spectrum covers:
- Candida species — exhibit a fungicidal effect. They remain active even against strains resistant to other antifungals, including Candida glabrata and Candida krusei.
- Aspergillus species — exhibit a fungistatic effect, halting fungal growth.
General Pharmacokinetics and Safety
All echinocandins are administered exclusively parenterally due to poor oral bioavailability and lack of gastrointestinal absorption.
- Tolerability: Overall tolerability is favorable, comparable to fluconazole.
- Adverse effects: Headache, fever, elevated liver enzymes, and rare hemolysis.
- Histamine-like reactions: Infusion-related reactions such as rash, pruritus, and bronchospasm may occur due to histamine release triggered by the peptide chain.
Clinical Applications of Representatives
Each agent has distinct clinical indications:
- Caspofungin: The first-in-class agent, used for esophageal candidiasis, candidemia, invasive aspergillosis ("salvage therapy"), and empirical therapy for febrile neutropenia.
- Micafungin: Derived from Coleophoma empedri, used for esophageal candidiasis and prophylaxis of fungal infections in hematopoietic stem cell transplant recipients.
- Anidulafungin: Derived from Aspergillus nidulans, indicated for esophageal candidiasis and candidemia. It is compatible with combination therapy involving amphotericin B, flucytosine, or azoles.