Article: article from journal or magazin.
Potential Microbiological Effects of Higher Dosing of Echinocandins.
Clinical Infectious Diseases
61 Suppl 6
The antifungal "paradoxical effect" has been described as the reversal of growth inhibition at high doses of echinocandins, most usually caspofungin. This microbiological effect appears to be a cellular compensatory response to cell wall damage, resulting in alteration of cell wall content and structure as well as fungal morphology and growth. In vitro studies demonstrate this reproducible effect in a certain percentage of fungal isolates, but animal model and clinical studies are less consistent. The calcineurin and Hsp90 cell signaling pathways appear to play a major role in regulating these cellular and structural changes. Regardless of the clinical relevance of this paradoxical growth effect, understanding the specific actions of echinocandins is paramount to optimizing their use at either standard or higher dosing schemes, as well as developing future improvements in our antifungal arsenal.
Animals, Antifungal Agents/administration & dosage, Antifungal Agents/adverse effects, Aspergillosis/drug therapy, Aspergillosis/microbiology, Aspergillus/drug effects, Aspergillus/growth & development, Calcineurin/metabolism, Candida/drug effects, Candida/genetics, Candidiasis/drug therapy, Candidiasis/microbiology, Cell Wall/drug effects, Cell Wall/metabolism, Clinical Trials as Topic, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Tolerance, Echinocandins/administration & dosage, Echinocandins/adverse effects, Fungal Proteins/metabolism, HSP90 Heat-Shock Proteins/metabolism, Humans
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