Investigating auranofin for the treatment of infected diabetic pressure ulcers in mice and dermal toxicity in pigs.

ABSTRACT

Bacterial infection of pressure ulcers (PUs) are a notable source of hospitalization for individuals with diabetes. This study evaluated the safety profile and efficacy of auranofin to treat diabetic PUs infected with methicillin-resistant Staphylococcus aureus (MRSA). PUs were infected with MRSA in diabetic TALLYHO/JngJ mice and then treated with topical auranofin (2%), topical mupirocin (2%), or oral clindamycin (30 mg/kg) for four days. PUs were harvested post-treatment to enumerate bacterial burden and determine expression of cytokines/growth factors. Landrace cross pigs were exposed topically to auranofin (1%, 2%, and 3%) for 4-14 days and evaluated for signs of localized or systemic toxicity. Auranofin eradicated MRSA in PUs within four days (7.92-log10 reduction) in contrast to mupirocin (2.15-log10 reduction) and clindamycin (0.73-log10 reduction). Additionally, auranofin treatment resulted in decreased expression of pro-inflammatory cytokines and increased expression of biomarkers associated with re-epithelization of wounded tissue, confirmed with histopathologic analysis. No significant histopathologic lesions were present on porcine skin sites exposed to topical auranofin. Additionally, minimal accumulation of plasma gold and no systemic toxicity was observed in pigs exposed to topical auranofin. Auranofin appears to be a potent and safe topical agent to further investigate for treatment of mild-to-moderate MRSA-infected diabetic PUs.