Preclinical Results

Chelators Restore Lost Potency of Antibiotics Against Resistant Bacteria

CP’s chelators DIBI and JSM-11 have been proven effective against the growth of Gram-positive bacteria (e.g., Staphylococcus aureus), Gram-negative bacteria (e.g., Escherichia coli , Pseudomonas aeruginosa, Acinetobacter baumannii), and fungi (e.g., Candida albicans) in laboratory culture.More importantly, while commonly used antibiotics are failing to combat resistant infections, small addition of DIBI or JSM-11 is able to completely restore the efficacy of kanamycin and gentamycin to a resistant strain of MRSA by depleting iron in standard laboratory bacterial susceptibility tests.  DIBI also enhances antibiotic potency against drug sensitive strains (no resistance acquired).

Chelators Enhance the Efficacy of Standard Antifungal Therapy

Acting alone, DIBI can inhibit fungal growth with effects comparable to itraconazole. However, small additions of the chelator DIBI are able to significantly enhance the antifungal efficacy by 1,000-10,000 fold in a standard laboratory susceptibility test.  The antifungal effects of DIBI are dose-dependent; the higher the concentration of DIBI, the more significant growth inhibition.

Chelators Effective in Proof-of-Concept Animal Study

In the mouse model, the combination of DIBI and fusidic acid (below therapeutic concentration) can achieve 10 times better therapeutic efficacy against MRSA in mouse skin infection model compared to fusidic acid at clinical therapeutic concentration. This study demonstrated important synergy observed when CP’s chelator and fusidic acid are dosed in combination in vivo.

DEMONSTRATION OF IN VIVO SYNERGY

DERMAL INFECTION (4 DAYS)

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