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Published on: September 28, 2021
In vitro evaluation of combination of polyenes with EDTA against Aspergillus spp. by different methods (FICI and CI
1Centre for Biotechnology, Maharshi Dayanand University, Rohtak, Haryana, India.
Aims:
We investigated in vitro activity of polyene drugs (amphotericin B, Amp B; and nystatin, NYS;) in combination with ethylene diamine tetra acetic acid (EDTA) against 8 pathogenic isolates of Aspergillus spp.
Methods And Results:
The intensity of the drug interactions was assessed using Fractional Inhibitory Concentration Index (FICI) model and Combination Index (CI) model. The interactions were further confirmed by time-kill curve study. The best combination ratio was subjected for toxicity analysis by MTT and haemolytic assay. A significant synergy was found between each of two polyenes with EDTA against Aspergillus fumigatus and Aspergillus flavus at one ratio four. The FICI ranged from 0·29 to 0·38 against A. fumigatus and A. flavus. The FICI value ranged from 0·78 to 1·26 showed no interaction against Aspergillus niger. The CI value (0·21-0·30) and time-kill curve analysis also confirmed synergistic interaction. Antagonism was not detected. There was reduction in toxicity of Amp B and NYS when used with EDTA.
Conclusions:
Subsequently, the chelating agent (EDTA) can be used in combination with Amp B and NYS with increased antifungal potential and reduced toxicity.
Significance And Impact Of The Study:
To emphasize new development in antifungal drug discovery, combination therapy can be used as a tool box to expand drug development.
Insights
Ethylene diamine tetra acetic acid (EDTA) combined with amphotericin B (Amp B) and nystatin (NYS) showed synergistic antifungal activity against Aspergillus fumigatus and Aspergillus flavus. This combination also reduced drug toxicity.
Area of Science:
- Mycology
- Pharmacology
- Infectious Diseases
Background:
- Polyene antifungal drugs like amphotericin B (Amp B) and nystatin (NYS) are crucial for treating Aspergillus infections.
- Developing novel therapeutic strategies is essential due to rising antifungal resistance and drug toxicity concerns.
Purpose of the Study:
- To investigate the in vitro synergistic potential of Amp B and NYS in combination with ethylene diamine tetra acetic acid (EDTA).
- To evaluate the impact of this combination on antifungal activity and toxicity against pathogenic Aspergillus species.
Main Methods:
- In vitro activity assessment using Fractional Inhibitory Concentration Index (FICI) and Combination Index (CI) models.
- Time-kill curve studies and toxicity analyses (MTT and haemolytic assays) were performed.
Main Results:
- Significant synergy was observed between polyenes (Amp B, NYS) and EDTA against Aspergillus fumigatus and Aspergillus flavus.
- Fractional Inhibitory Concentration Index (FICI) values indicated synergy (0.29–0.38), while no interaction was seen against Aspergillus niger (0.78–1.26).
- Combination therapy demonstrated reduced toxicity of Amp B and NYS.
Conclusions:
- EDTA can enhance the antifungal potential of Amp B and NYS, offering a promising combination therapy.
- Combination therapy represents a valuable strategy for antifungal drug discovery and development.
