New developments and directions in the clinical application of the echinocandins.
The echinocandins-caspofungin, anidulafungin and micafungin-are semi-synthetic cyclic hexapeptide antimicrobial agents with modified N-linked acyl lipid side chains which anchor the compounds to the phospholipid bilayer of the fungal cell membrane, thereby inhibiting synthesis of fungal cell wall glucan. Over the last 10 years, echinocandins have become the first-line antifungal treatment of candidaemia and other forms of invasive candidiasis (IC). Echinocandins are generally well tolerated, but their use is limited by their requirement for daily intravenous dosing, lack of oral formulation and limited spectrum. In critically ill patients, it is also recognised that achievement of their pharmacokinetic/pharmacodynamic targets shows large inter-individual variability. As a drug class, they are safe to use and are associated with few adverse reactions and few drug-drug interactions of significance. Recent discovery of their ability to prevent and treat Candida biofilm formation particularly in the presence of invasive medical devices and also their ability to penetrate into mucosal surfaces such as vulvovaginal candidiasis has opened up new opportunities for research into their drug delivery. New dosing intervals are being explored to allow less frequent intravenous dosing in the ambulatory setting, and a new long-acting echinocandin, CD101, is being developed for weekly and topical administration.
Department of Infectious Diseases, Alfred Hospital, Monash University, Melbourne, Australia.
C C
CC
Chang
Department of Infectious Diseases, Peter MacCallum Hospital, Victorian Comprehensive Care Centre, Melbourne, Australia.|Victorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne, Australia.
M A
MA
Slavin
Marie Bashir Institute for Emerging Infectious Diseases and Biosecurity, University of Sydney, Sydney, Australia. Sharon.chen@health.nsw.gov.au.|Centre for Infectious Diseases and Microbiology Laboratory Services, 3rd Level, ICPMR Building - Pathology West, Westmead Hospital, Darcy Road, Westmead, Sydney, NSW, 2145, Australia. Sharon.chen@health.nsw.gov.au.
S C-A
SC
Chen
D061605:Administration, Intravenous; D000077612:Anidulafungin; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D018441:Biofilms / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy*; D000077336:Caspofungin; D004334:Drug Administration Schedule; D004347:Drug Interactions; D054714:Echinocandins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D055666:Lipopeptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000077551:Micafungin
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077612:Anidulafungin; D000077336:Caspofungin; D000077551:Micafungin
Adverse effects; Anidulafungin; Biofilm; CD101; Caspofungin; Echinocandins; Invasive candidiasis; Micafungin