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Interaction of Amiodarone with Azoles Against Aspergillus Planktonic Cells and Biofilms in vitro
Zhimin Duan1, Jianbo Tong2, Nana Zheng1
1Hospital for Skin Diseases (Institute of Dermatology), Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, Jiangsu, China.
Abstract:
Aspergillus spp. is the most common clinical pathogen of invasive fungal infection with high mortality. Existing treatments for Aspergillus spp. infection are still inefficient and accompanied by drug resistance, so it is still urgent to find new treatment approaches. The antiarrhythmic drug amiodarone (AMD) has demonstrated antifungal activity against a range of fungi. This study evaluated the efficacy of AMD in combination with triazoles for Aspergillus spp. infection. We tested the combined effect of AMD and three triazole drugs, namely, itraconazole (ITR), voriconazole (VRC), and posaconazole (POS), on the planktonic cells and biofilms of 20 strains of Aspergillus spp. via a checkerboard microdilution assay derived from 96-well plate-based method. Our results reveal that the combination of AMD with ITR or POS against Aspergillus biofilms has synergistic fungicidal effects. By contrast, the combination of AMD with VRC exhibits no antagonistic and synergistic effects. In this way, the use of AMD in combination with ITR or POS could be an effective adjunctive treatment for Aspergillus spp. infection.
Insights
Amiodarone (AMD) combined with itraconazole or posaconazole shows synergistic antifungal effects against Aspergillus biofilms. This combination offers a promising adjunctive therapy for invasive fungal infections caused by Aspergillus species.
Area of Science:
- Mycology
- Pharmacology
- Infectious Diseases
Background:
- Aspergillus species are leading causes of invasive fungal infections with high mortality rates.
- Current treatments for Aspergillus infections face challenges with inefficiency and emerging drug resistance.
- Amiodarone (AMD), an antiarrhythmic drug, exhibits known antifungal properties against various fungi.
Purpose of the Study:
- To evaluate the efficacy of amiodarone (AMD) in combination with triazole antifungals against Aspergillus species.
- To assess the synergistic or antagonistic effects of AMD combined with itraconazole (ITR), voriconazole (VRC), and posaconazole (POS).
- To investigate the impact on both planktonic Aspergillus cells and biofilms.
Main Methods:
- Utilized a checkerboard microdilution assay based on a 96-well plate method.
- Tested the combined effects of AMD with ITR, VRC, and POS against 20 strains of Aspergillus species.
- Evaluated activity against planktonic cells and fungal biofilms.
Main Results:
- AMD demonstrated synergistic fungicidal effects when combined with itraconazole (ITR) or posaconazole (POS) against Aspergillus biofilms.
- The combination of AMD with voriconazole (VRC) showed neither synergistic nor antagonistic effects.
- No significant synergistic or antagonistic effects were observed for planktonic cells.
Conclusions:
- Combination therapy of amiodarone (AMD) with itraconazole (ITR) or posaconazole (POS) presents a potential effective adjunctive treatment strategy for Aspergillus infections.
- These synergistic combinations specifically target Aspergillus biofilms, a critical aspect of invasive fungal infections.
- Further research into AMD-based combination therapies could lead to improved outcomes for patients with invasive aspergillosis.
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