Echinocandins for Fluconazole-Resistant Candida

[Guest guest]

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 β-(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.

 

http://www.theannals.com/cgi/content/abstract/43/10/1647