The echinocandin antifungals: an overview of the pharmacology, spectrum and clinical efficacy.
For over four decades, the principal target of antifungal therapy has been the fungal cell membrane sterol ergosterol. Although this has proven to be a successful and relatively selective antifungal target, collateral toxicity to mammalian cells (amphotericin B) and drug interactions (azoles) have been by-products of agents that target the fungal cell membrane. In the 1970s, the echinocandins were identified during the screening of fungal fermentation products for new antibiotic agents. These agents were subsequently shown to inhibit production of beta(1,3)-glucan, a key structural component of the fungal cell wall. Subsequent chemical modification of these natural products has led to the development of safer, semi-synthetic beta(1,3)-glucan synthase inhibitors with enhanced microbiological and clinical efficacy against infections caused by Candida and Aspergillus species. In this review, the pharmacology, spectrum and clinical efficacy of the three leading beta(1,3)glucan synthase inhibitors (caspofungin, micafungin and anidulafungin), which have completed phase III clinical trials, will be discussed and a perspective for the role of these agents in the management of life-threatening mycoses will be offered.
Wiederhold
Nathan P
NP
University of Houston College of Pharmacy, 1441 Moursund St 423, Houston TX, 77030, USA. rlewis@uh.edu
Lewis
Russell E
RE
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D054714:Echinocandins; D005656:Fungal Proteins; D005658:Fungi / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009181:Mycoses / Q000188:drug therapy*; D010455:Peptides; D010456:Peptides, Cyclic; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D054714:Echinocandins; D005656:Fungal Proteins; D010455:Peptides; D010456:Peptides, Cyclic; C007572:echinocandin B