Echinocandins: The Newest Class of Antifungals

OBJECTIVE: To review the mechanism of action, antifungal spectrum of activity, pharmacodynamics, pharmacokinetics, clinical efficacy and safety of the echinocandins. DATA SOURCES: A MEDLINE search (1982-May 2009) was conducted for articles published in the English language using the key words caspofungin, micafungin, anidulafungin, and echinocandins. STUDY SELECTION AND DATA EXTRACTION: Medicinal chemistry, in vitro, and animal studies, as well as human trials were reviewed for information on the pharmacodynamics, pharmacokinetics, efficacy, and safety of each echinocandin. Clinical trials were reviewed and included to compare and contrast the available echinocandins. DATA SYNTHESIS: Three echinocandin antifungal agents are currently approved for use in the US: caspofungin, micafungin, and anidulafungin. The echinocandins have a unique mechanism of action, inhibiting beta-(1,3)-D-glucan synthase, an enzyme that is necessary for the synthesis of an essential component of the cell wall of several fungi. The echinocandins display fungistatic activity against Aspergillus spp. and fungicidal activity against most Candida spp., including strains that are fluconazole-resistant. The echinocandins have been shown to be efficacious for the treatment of esophageal candidiasis, candidemia, and invasive candidiasis. In addition, caspofungin has demonstrated efficacy as empiric treatment of febrile neutropenia and salvage therapy for the treatment of invasive aspergillosis, and it is the only echinocandin approved for use in pediatric patients. Micafungin is the only echinocandin approved for use as prophylaxis against Candida infections in patients undergoing hematopoietic stem cell transplantation. Overall, resistance to echinocandins is still rare, and all agents are well tolerated, with similar adverse effect profiles and few drug-drug interactions. CONCLUSIONS: Echinocandins, the newest addition to the arsenal of antifungals, offer potential advantages over other classes of agents. Clinicians should assess their distinguishing characteristics, including route of metabolism, drug interaction profile, and approved indications for use, when determining which agent to include on a formulary.