Echinocandins are antifungal drugs that inhibit the synthesis of glucan in the cell wall, probably via noncompetitive inhibition of the enzyme 1,3-β glucan synthase[1][2] and are thus called penicillin of antifungals (a property shared with papulacandins). Beta glucans are polymers which, linked in their tens of thousands, make up cell wall membranes. Some other examples are cellulose and starches in the plant world, and glycogen and dextran in the animal world, made from alpha glucans.
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It is used in candidiasis and aspergillosis.[3]
They are fungicidal against some yeasts (most species of Candida, but not against Cryptococcus, Trichosporon and Rhodotorula), fungistatic against some molds (Aspergillus, but not Fusarium and Rhizopus), and modestly or minimally active active against dimorphic fungi (Blastomyces and Histoplasma). These have some activity against the spores of the fungus Pneumocystis carinii.
The present day clinically used echinocandins are semisynthetic pneumocandins, which are chemically lipopeptide in nature, consisting of large cyclic (hexa)peptides linked to a long chain fatty acid. Discovery of echinocandins stemmed from studies on papulacandins isolated from a strain of Papularia sphaerosperma (Pers.), which were liposaccharide, i.e., fatty acid derivatives of a disaccharide which also blocked the same target, 1,3-β glucan synthase, and had action only on Candida spp. (narrow spectrum). Screening of natural products of fungal fermentation in the 1970s led to the discovery of echinocandins, a new group of antifungals with broad range activity against Candida spp. One of the first echinocandins of the pneumocandin type, discovered in 1974, echinocandin B, could not be used clinically due to risk of high degree of hemolysis. Screening semisynthetic analogs of the echinocandins gave rise to cilofungin, the first echinofungin analog to enter clinical trials, in 1980, which was later withdrawn for a toxicity presumably due to the solvent system needed for systemic administration. The semisynthetic pneumocandin analogs of echinocandins were later found to have the same kind of antifungal activity, but low toxicity. The first approved of these newer echinocandins was caspofungin, and later micafungin and anidulafungin were also approved. All these preparations so far have low oral bioavailability, so must be given intravenously only. Echinocandins have now become one of the first line treatments for Candida before the species are identified, and even as antifungal prophylaxis in hematopoietic stem cell transplant patients.
Advantages of echinocandins:
Disadvantages of echinocandins:
Caspofungin has some interference with ciclosporin metabolism, and micafungin has some interference with sirolimus (rapamycin), but anidulafungin needs no dose adjustments when given with ciclosporin, tacrolimus or voriconazole.[6]
List of echinocandins:
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