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

摘要

In the second year, a cutaneous wound model in rats with the drug resistant Gram negative bacteria Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and pathogenic mold Aspergillus fumigatus was established. Efficacy of CHD-FA against cutaneous wounds infected with these organisms was assessed respectively. Significant wound surface area reduction with high and mid CHD-FA treatment doses was observed with all studied infection models. Remarkable bioburden reduction induced by CHD-FA was also observed in wounds infected with multidrug resistant E. coli and K. pneumoniae. To better assess wound healing upon CHD-FA treatment at cellular and molecular level, a more comprehensive histopathological evaluation and expression profiling of wound healing genes was performed at various time points during the infection/treatment course in rats infected with MRSA and P. aeruginosa, respectively. Histopathological analysis showed that the infection and inflammation in the wounds from both infection models treated with CHD-FA was better controlled relative to the untreated and antibiotic control groups, as indicated by lower neutrophils scores as early as day 3. The decrease in cellular inflammation and increase in epithelialization at the endpoint of the experiment suggested wound healing was significantly improved with CHD-FA treatment. Host gene expression profiling displayed the same dynamic trend of differentially expressed wound healing genes upon CHD-FA treatment in both infection models. The levels of overexpression were found to be more prominent in the CHD-FA group at day 3 compared to the untreated control, and their expression levels rapidly returned towards baseline at day 6, as the same set of genes in the untreated control increased.