Abstract
Atopic dermatitis (AD) is a skin disorder characterized by reduced skin barrier function, which often leads to recurring infections, predominantly by Staphylococcus aureus and methicillin-resistant S. aureus, that exacerbate disease severity. Managing these infections is made challenging by antibiotic resistance and biofilm formation. Nitric oxide (NO) has emerged as a promising antimicrobial treatment that can disperse biofilm and may provide an alternative treatment for AD infections.BACKGROUNDAtopic dermatitis (AD) is a skin disorder characterized by reduced skin barrier function, which often leads to recurring infections, predominantly by Staphylococcus aureus and methicillin-resistant S. aureus, that exacerbate disease severity. Managing these infections is made challenging by antibiotic resistance and biofilm formation. Nitric oxide (NO) has emerged as a promising antimicrobial treatment that can disperse biofilm and may provide an alternative treatment for AD infections.This study evaluated the antimicrobial efficacy of 3 topical NO-releasing formulations at various concentrations against established MRSA infections, from an AD-derived isolate, in a porcine wound infection model. Partial thickness wounds were inoculated and, after 48 hours of biofilm formation, were treated daily with NO formulations or vehicle control, or left untreated. Wounds were recovered for baseline, day 4, or day 7 bacterial enumeration.METHODSThis study evaluated the antimicrobial efficacy of 3 topical NO-releasing formulations at various concentrations against established MRSA infections, from an AD-derived isolate, in a porcine wound infection model. Partial thickness wounds were inoculated and, after 48 hours of biofilm formation, were treated daily with NO formulations or vehicle control, or left untreated. Wounds were recovered for baseline, day 4, or day 7 bacterial enumeration.All tested NO-releasing formulations substantially reduced MRSA burden compared with baseline counts, and most effectively with the highest concentrations. 20% NO+GEL resulted in a significant reduction of 99.23% compared with baseline at day 7. The 16% NO+UNG treatment, compared with the untreated control, had bacterial reductions on day 4 and day 7 of greater than 99.5%. The greatest reduction of 99.97% (>3 Log CFU/mL) was observed for 6% NO+CREAM compared with the untreated control group at day 7.RESULTSAll tested NO-releasing formulations substantially reduced MRSA burden compared with baseline counts, and most effectively with the highest concentrations. 20% NO+GEL resulted in a significant reduction of 99.23% compared with baseline at day 7. The 16% NO+UNG treatment, compared with the untreated control, had bacterial reductions on day 4 and day 7 of greater than 99.5%. The greatest reduction of 99.97% (>3 Log CFU/mL) was observed for 6% NO+CREAM compared with the untreated control group at day 7.NO-releasing treatments have considerable efficacy against MRSA infections and biofilm. These findings support the potential of NO as an antimicrobial treatment for AD patients, and further evaluation should be conducted to assess clinical efficacy.CONCLUSIONSNO-releasing treatments have considerable efficacy against MRSA infections and biofilm. These findings support the potential of NO as an antimicrobial treatment for AD patients, and further evaluation should be conducted to assess clinical efficacy.