title: Carbohydrate-derived fulvic acid is a highly promising topical agent to enhance healing of wounds infected with drug-resistant pathogens.
abstract: BACKGROUND
  This work was intended as a proof-of-principle study to help establish carbohydrate-derived fulvic acid (CHD-FA) as a safe and effective agent that can be deployed to prevent the onset of drug-resistant bacterial and fungal infections in military and civilian personnel experiencing traumatic wound.
  
  
  METHODS
  Minimum inhibitory concentrations for CHD-FA were established on a total of 500 clinical isolates representing wound-associated drug-sensitive and drug-resistant bacterial and fungal pathogens. The efficacy of early use of CHD-FA to enhance healing of wounds infected with methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa was evaluated in an in vivo rat model.
  
  
  RESULTS
  CHD-FA showed strong activity against a variety of bacterial and fungal pathogens with minimum inhibitory concentration values equal or less than 0.5%. Compared with infected but untreated wounds, improved wound healing upon CHD-FA treatment was observed in both infection models, demonstrated by wound surface area measurement, histopathologic examination, and expression profiling of wound healing genes. Up-regulation of proinflammatory cytokine interleukin 6 (IL-6) at Day 3 after infection was significantly dampened at Days 6 and 10 in the CHD-FA-treated wounds in both infection models, displaying an improved and accelerated wound healing.
  
  
  CONCLUSIONS
  CHD-FA is a promising topical remedy for drug-resistant wound infections. It accelerated the healing process of wounds infected with methicillin-resistant S. aureus and multidrug-resistant P. aeruginosa in rats, which is linked to both its antimicrobial and anti-inflammatory properties.
authors.affiliation: From the Public Health Research Institute (Y.Z., P.P., G.D., E.D., M.H.L., M.S., S.P., D.S.P.), Rutgers Biomedical and Health Sciences, Newark, New Jersey; and Fulhold, Ltd. (S.L.), Ebene Mews, Mauritius.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Padmaja
authors.initials: P
authors.lastname: Paderu
authors.forename: Guillaume
authors.initials: G
authors.lastname: Delmas
authors.forename: Enriko
authors.initials: E
authors.lastname: Dolgov
authors.forename: Min Hee
authors.initials: MH
authors.lastname: Lee
authors.forename: Meredith
authors.initials: M
authors.lastname: Senter
authors.forename: Steven
authors.initials: S
authors.lastname: Park
authors.forename: Stephen
authors.initials: S
authors.lastname: Leivers
authors.forename: David S
authors.initials: DS
authors.lastname: Perlin
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D001578:Benzopyrans / Q000008:administration & dosage / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008826:Microbial Sensitivity Tests; D009181:Mycoses / Q000188:drug therapy* / Q000382:microbiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D014945:Wound Healing / Q000187:drug effects*; D014946:Wound Infection / Q000188:drug therapy* / Q000382:microbiology*
chemical_list: D000900:Anti-Bacterial Agents; D001578:Benzopyrans; D015850:Interleukin-6; C005023:fulvic acid