In vitro evaluation of combination of polyenes with EDTA against Aspergillus spp. by different methods (FICI and CI Model)
Article first published online: 13 JUL 2014
© 2014 The Society for Applied Microbiology
Journal of Applied Microbiology
Volume 117, Issue 3, pages 643–653, September 2014
How to Cite
Ruhil, S., Kumar, V., Balhara, M., Malik, M., Dhankhar, S., Kumar, M. and Kumar Chhillar, A. (2014), In vitro evaluation of combination of polyenes with EDTA against Aspergillus spp. by different methods (FICI and CI Model). Journal of Applied Microbiology, 117: 643–653. doi: 10.1111/jam.12576
- Issue published online: 18 AUG 2014
- Article first published online: 13 JUL 2014
- Accepted manuscript online: 16 JUN 2014 01:39AM EST
- Manuscript Accepted: 11 JUN 2014
- Manuscript Revised: 22 MAY 2014
- Manuscript Received: 17 MAR 2014
- Council of Scientific and Industrial Research (CSIR)
- Aspergillus spp.;
- combination index;
- EDTA ;
- fractional inhibitory concentration index;
- MTT assay;
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.
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.