title: Potential Microbiological Effects of Higher Dosing of Echinocandins.
abstract: 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.
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina.
authors.forename: William J
authors.initials: WJ
authors.lastname: Steinbach
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics Infectious Diseases Service, Department of Medicine Institute of Microbiology, Lausanne University Hospital, Switzerland.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lamoth
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics.
authors.forename: Praveen R
authors.initials: PR
authors.lastname: Juvvadi
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001228:Aspergillosis / Q000188:drug therapy* / Q000382:microbiology; D001230:Aspergillus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D019703:Calcineurin / Q000378:metabolism; D002175:Candida / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology; D000077336:Caspofungin; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D054714:Echinocandins / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D005656:Fungal Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D055666:Lipopeptides
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D005656:Fungal Proteins; D018841:HSP90 Heat-Shock Proteins; D055666:Lipopeptides; D019703:Calcineurin; D000077336:Caspofungin
keywords: Hsp90; calcineurin; cell wall; echinocandin; paradoxical effect