Evaluation of Carbohydrate-Derived Fulvic Acid (CHD-FA) as a Topical Broad-Spectrum Antimicrobial for Drug-Resistant Wound Infections

In the third year, the effect of pH changes on the bactericidal behavior of CHD-FA was assessed in vitro against medically important bacteria. The potent bactericidal activity of CHD-FA was significantly diminished and became bacteriostatic only when the pH was increased from 1.7 to 7.0. Upon establishing the burn wounds, the in vivo efficacy of CHD-FA to treat burn wounds infected with multidrug resistant Gram-negative bacteria K. pneumoniae or Gram-positive bacteria MRSA was evaluated. In all these trials, histopathological analyses and wound healing gene expression profiling demonstrated alleviated inflammation and promoted healing upon CHD-FA treatment, however no significant bacterial burden reduction was observed from CHD-FA treated wounds. Thereafter, different formulations of CHD-FA were assessed for improved in vivo antimicrobial potency on both cutaneous and burn wounds. CHD-FA zinc diacetate CHD-FA-Zn was found the most promising. In the MRSA infection study, bacteria were completely eliminated from infected wounds as rapidly as 24h post-inoculation upon CHD-FA-Zn application. Promising in vivo antimicrobial efficacy was also observed in the short-course P. aeruginosa study. However, the microbial burdens restored rapidly from day 3 in the 6-day study. The biofilm matrix formed on day 3 post-inoculation may be restricting the penetration of the drug. During the next quarter and throughout this next year, we will perform studies with a modified application method dressing to enhance absorption of drugs through the burn wound eschar and the biofilm matrix. Overall, we have made significant progress in the third year in demonstrating the value of CHD-FA to treat wound infections. We believe that the CHD-FA-Zn combined with the modified application method will be effective in treating wounds infected with major multi drug resistant pathogens and demonstrate its universality for preventing wound infections and promote healing.