Echinocandin pharmacodynamics: review and clinical implications

J Antimicrob Chemother. 2010 Jun;65(6):1108-18. doi: 10.1093/jac/dkq081. Epub 2010 Mar 23.

Abstract

Echinocandins have made a significant impact in the treatment of select invasive fungal infections, most notably invasive candidiasis and aspergillosis. However, treatment outcomes for such infections are still less than optimal, prompting an examination of dosing and administration techniques in an attempt to exploit known pharmacodynamic properties and improve outcomes. Echinocandins generally exhibit concentration-dependent, fungicidal activity against Candida spp. and fungistatic activity against Aspergillus spp. However, increasing drug concentrations of echinocandins above the organism's MIC may result in a paradoxical increase in fungal growth as demonstrated in some in vitro and in vivo models (known most commonly as the 'Eagle effect'). Therefore, the potential impact of dose escalations on improving the clinical efficacy of echinocandins based on in vitro and animal models are uncertain and are still being evaluated. In addition, such strategies have to consider the potential for increased treatment-related toxicities and costs. To date, published clinical studies (both superiority and non-inferiority) demonstrating the potential for dose-related improvements in treatment outcomes have been limited to mucocutaneous and oesophageal candidiasis. Further research is needed to determine if a role exists for optimizing echinocandin pharmacodynamics in various clinical settings.

Publication types

  • Review

MeSH terms

  • Animals
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / adverse effects
  • Antifungal Agents / pharmacokinetics*
  • Antifungal Agents / pharmacology*
  • Aspergillosis / drug therapy*
  • Candidiasis / drug therapy*
  • Disease Models, Animal
  • Echinocandins / administration & dosage
  • Echinocandins / adverse effects
  • Echinocandins / pharmacokinetics*
  • Echinocandins / pharmacology*
  • Humans
  • Microbial Sensitivity Tests
  • Microbial Viability / drug effects
  • Treatment Outcome

Substances

  • Antifungal Agents
  • Echinocandins