Echinocandin

Caspofungin, micafungin, and anidulafungin are semisynthetic echinocandin derivatives with limited clinical use due to their solubility, antifungal spectrum, and pharmacokinetic properties.

Echinocandins are fungistatic against some molds (Aspergillus, but not Fusarium and Rhizopus), and modestly or minimally active against dimorphic fungi (Blastomyces and Histoplasma).

Caspofungin, micafungin, and anidulafungin are similar cyclic hexapeptide antibiotics linked to long modified N-linked acyl fatty acid chains.

[10] Echinocandins noncompetitively inhibit beta-1,3-D-glucan synthase enzyme complex in susceptible fungi to disturb fungal cell glucan synthesis.

[15] Several non-candidal yeasts, e.g., Cryptococcus, Trichosporon, Rhodotorula and Blastoschizomyces and filamentous fungi like Fusarium, zygomycetes and Scedosporium are often resistant to echinocandins.

[16] Echinocandins have weak in vitro activity (a high minimum inhibitory concentration) and very little clinical efficacy against Histoplasma, Blastomyces, and Coccidioides, especially their yeast forms.

Caspofungin has triphasic nonlinear pharmacokinetics, while micafungin (hepatically metabolized by arylsulfatase, catechol O-methyltransferase, and hydroxylation) and anidulafungin (degraded spontaneously in the system and excreted mostly as a metabolite in the urine) have linear elimination.

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.

Echinocandins have 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.