New developments and directions in the clinical application of the echinocandins

Arch Toxicol. 2017 Apr;91(4):1613-1621. doi: 10.1007/s00204-016-1916-3. Epub 2017 Feb 8.

Abstract

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.

Keywords: Adverse effects; Anidulafungin; Biofilm; CD101; Caspofungin; Echinocandins; Invasive candidiasis; Micafungin.

Publication types

  • Review

MeSH terms

  • Administration, Intravenous
  • Anidulafungin
  • Animals
  • Antifungal Agents / administration & dosage*
  • Antifungal Agents / adverse effects
  • Antifungal Agents / therapeutic use
  • Biofilms / drug effects
  • Candidiasis / drug therapy*
  • Caspofungin
  • Drug Administration Schedule
  • Drug Interactions
  • Echinocandins / administration & dosage*
  • Echinocandins / adverse effects
  • Echinocandins / therapeutic use
  • Humans
  • Lipopeptides / administration & dosage*
  • Lipopeptides / adverse effects
  • Lipopeptides / therapeutic use
  • Micafungin

Substances

  • Antifungal Agents
  • Echinocandins
  • Lipopeptides
  • Anidulafungin
  • Caspofungin
  • Micafungin