Attenuation of echinocandin activity at elevated concentrations: A review of the paradoxical effect

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Abstract

PURPOSE OF REVIEW: The echinocandins have been a welcome addition for the treatment of invasive fungal infections caused by Candida and Aspergillus species. Despite their excellent safety profile and clinical efficacy, concerns exist regarding an attenuation of activity at higher concentrations, known as the paradoxical effect. This article will review the literature describing this effect, the potential mechanisms responsible for it, and the clinical implications of this phenomenon. RECENT FINDINGS: In-vitro studies have reported a paradoxical effect at higher concentrations against both Candida and Aspergillus species. Recent data have demonstrated this effect in Candida to be species related and echinocandin specific. Although not completely understood, studies have pointed towards involvement of the protein kinase C cell wall integrity and calcineurin pathways as well as increases in cell wall chitin content as potential mechanisms behind the effect. Although some in-vivo studies with echinocandins have reported a paradoxical increase in markers of invasive disease, clinical data are scarce. SUMMARY: The clinical implications of the paradoxical attenuation of echinocandin activity observed in vitro and in vivo remain unknown. A complete understanding of this effect may further our knowledge of fungal responses to echinocandin cell wall damage and potentially improve treatment strategies.

Original languageEnglish (US)
Pages (from-to)574-578
Number of pages5
JournalCurrent Opinion in Infectious Diseases
Volume20
Issue number6
DOIs
StatePublished - Dec 2007

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Echinocandins
Candida
Cell Wall
Aspergillus
Chitin
Calcineurin
Protein Kinase C
Safety

Keywords

  • Anidulafungin
  • Aspergillus
  • Candida
  • Caspofungin
  • Echinocandins
  • Micafungin
  • Paradoxical effect

ASJC Scopus subject areas

  • Microbiology (medical)
  • Immunology

Cite this

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abstract = "PURPOSE OF REVIEW: The echinocandins have been a welcome addition for the treatment of invasive fungal infections caused by Candida and Aspergillus species. Despite their excellent safety profile and clinical efficacy, concerns exist regarding an attenuation of activity at higher concentrations, known as the paradoxical effect. This article will review the literature describing this effect, the potential mechanisms responsible for it, and the clinical implications of this phenomenon. RECENT FINDINGS: In-vitro studies have reported a paradoxical effect at higher concentrations against both Candida and Aspergillus species. Recent data have demonstrated this effect in Candida to be species related and echinocandin specific. Although not completely understood, studies have pointed towards involvement of the protein kinase C cell wall integrity and calcineurin pathways as well as increases in cell wall chitin content as potential mechanisms behind the effect. Although some in-vivo studies with echinocandins have reported a paradoxical increase in markers of invasive disease, clinical data are scarce. SUMMARY: The clinical implications of the paradoxical attenuation of echinocandin activity observed in vitro and in vivo remain unknown. A complete understanding of this effect may further our knowledge of fungal responses to echinocandin cell wall damage and potentially improve treatment strategies.",
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