Combining Colistin and Fluconazole Synergistically Increases Fungal Membrane Permeability and Antifungal Cidality.
antifungal
azole
colistin
ergosterol synthesis
membrane permeabilization
yeast
Journal
ACS infectious diseases
ISSN: 2373-8227
Titre abrégé: ACS Infect Dis
Pays: United States
ID NLM: 101654580
Informations de publication
Date de publication:
12 02 2021
12 02 2021
Historique:
pubmed:
21
1
2021
medline:
24
6
2021
entrez:
20
1
2021
Statut:
ppublish
Résumé
The increasing emergence of drug-resistant fungal pathogens, together with the limited number of available antifungal drugs, presents serious clinical challenges to treating systemic, life-threatening infections. Repurposing existing drugs to augment the antifungal activity of well-tolerated antifungals is a promising antifungal strategy with the potential to be implemented rapidly. Here, we explored the mechanism by which colistin, a positively charged lipopeptide antibiotic, enhances the antifungal activity of fluconazole, the most widely used orally available antifungal. In a range of susceptible and drug-resistant isolates and species, colistin was primarily effective at reducing fluconazole tolerance, a property of subpopulations of cells that grow slowly in the presence of a drug and may promote the emergence of persistent infections and resistance. Clinically relevant concentrations of colistin synergized with fluconazole, reducing fluconazole minimum inhibitory concentration 4-fold. Combining fluconazole and colistin also increased survival in a
Identifiants
pubmed: 33471513
doi: 10.1021/acsinfecdis.0c00721
pmc: PMC7887753
doi:
Substances chimiques
Antifungal Agents
0
Fluconazole
8VZV102JFY
Colistin
Z67X93HJG1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
377-389Références
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