Echinocandins for the Treatment of Invasive Aspergillosis: from Laboratory to Bedside
| Autor: | Marion Aruanno, Frédéric Lamoth, Emmanouil Glampedakis |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Hyphal growth
Antifungal Agents Antifungal drug Pharmacology Aspergillosis Aspergillus fumigatus Echinocandins 03 medical and health sciences chemistry.chemical_compound polycyclic compounds medicine Humans Pharmacology (medical) HSP90 Heat-Shock Proteins 030304 developmental biology 0303 health sciences biology 030306 microbiology business.industry Micafungin bacterial infections and mycoses biology.organism_classification medicine.disease Infectious Diseases chemistry Host-Pathogen Interactions Anidulafungin Minireview Caspofungin business Invasive Fungal Infections medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 63 |
| ISSN: | 1098-6596 0066-4804 |
| Popis: | Echinocandins (caspofungin, micafungin, anidulafungin), targeting β-1,3-glucan synthesis of the cell wall, represent one of the three currently available antifungal drug classes for the treatment of invasive fungal infections. Despite their limited antifungal activity against Aspergillus spp., echinocandins are considered an alternative option for the treatment of invasive aspergillosis (IA). This drug class exhibits several advantages, such as excellent tolerability and its potential for synergistic interactions with some other antifungals. The objective of this review is to discuss the in vitro and clinical efficacy of echinocandins against Aspergillus spp., considering the complex interactions between the drug, the mold, and the host. The antifungal effect of echinocandins is not limited to direct inhibition of hyphal growth but also induces an immunomodulatory effect on the host’s response. Moreover, Aspergillus spp. have developed important adaptive mechanisms of tolerance to survive and overcome the action of echinocandins, such as paradoxical growth at increased concentrations. This stress response can be abolished by several compounds that potentiate the activity of echinocandins, such as drugs targeting the heat shock protein 90 (Hsp90)-calcineurin axis, opening perspectives for adjuvant therapies. Finally, the present and future places of echinocandins as prophylaxis, monotherapy, or combination therapy of IA are discussed in view of the emergence of pan-azole resistance among Aspergillus fumigatus isolates, the occurrence of breakthrough IA, and the advent of new long-lasting echinocandins (rezafungin) or other β-1,3-glucan synthase inhibitors (ibrexafungerp). |
| Databáze: | OpenAIRE |
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