title: In vitro evaluation of combination of polyenes with EDTA against Aspergillus spp. by different methods (FICI and CI Model).
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  To emphasize new development in antifungal drug discovery, combination therapy can be used as a tool box to expand drug development.
authors.affiliation: Centre for Biotechnology, Maharshi Dayanand University, Rohtak, Haryana, India.
authors.forename: S
authors.initials: S
authors.lastname: Ruhil
authors.forename: V
authors.initials: V
authors.lastname: Kumar
authors.forename: M
authors.initials: M
authors.lastname: Balhara
authors.forename: M
authors.initials: M
authors.lastname: Malik
authors.forename: S
authors.initials: S
authors.lastname: Dhankhar
authors.forename: M
authors.initials: M
authors.lastname: Kumar
authors.forename: A
authors.initials: A
authors.lastname: Kumar Chhillar
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001230:Aspergillus / Q000187:drug effects* / Q000302:isolation & purification; D065096:Calcium Chelating Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004357:Drug Synergism; D004492:Edetic Acid / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D009761:Nystatin / Q000494:pharmacology*; D011090:Polyenes / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D065096:Calcium Chelating Agents; D011090:Polyenes; D009761:Nystatin; D000666:Amphotericin B; D004492:Edetic Acid
keywords: Aspergillus spp.; EDTA; MTT assay; Polyene; combination index; fractional inhibitory concentration index; haemolytic; synergy