Advancement in Infection Control of Opportunistic Pathogen (Aspergillus spp.): Adjunctive Agents

Sonam      Ruhil; Meenakshi      Balhara; Sandeep      Dhankhar; Manish      Kumar; Vikash      Kumar; A.      K. Chhillar

doi:10.2174/1389201011314020013

Abstract

There is continuous emergence of resistant strains which leads to urgent need to discover new antifungal agents. The investigation of adjunctive agents for antifungal activity might help to optimize the therapy for Invasive Aspergillosis (IA). The chelating agents Ethylenediamine Tetraacetic Acid (EDTA) & Disodium salt of EDTA (DiEDTA) as adjunct to antifungal drugs have been investigated against 8 pathogenic isolates of Aspergillus spp. The MIC (Minimum Inhibitory Concentration) found by DDA (Disc Diffusion Assay) is 7.50-15.0 μg/disc; by MDA (Microbroth Dilution Assay) is 30.0-49.13 μg/ml & SGIA (Spore germination Inhibition Assay) is 30.0-49.13 μg/ml. Moreover, these agents did not show any toxicity up to a concentration of 312.5μg/ml. The antifungal activity is also confirmed by another method i.e time kill curve analysis. While these agents were ten times less active than gold standard drug (Amphotericin B; AmpB) but eight times less toxic than AmpB. This leads to preliminary investigation of in vitro combination of chelating agents with antifungal drugs (Polyenes & Azoles) by DDA. These combinations showed a significant increase in zone of inhibition in contrast to single drug used. This preliminary work with chelating agents suggest that EDTA as an enhancing agent with antifungal properties in combination with antifungal drugs can be used in pharmaceutical preparations. Further investigation is in progress.

Keywords: Adjunctive agent, Aspergillus spp., combination, chelating agent, invasive aspergillosis

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