Disulfiram's Anti-Inflammatory and Antibacterial Effects in Fixed-Dose Combination Therapy for Scabies

Background/Objectives: Scabies is a highly contagious parasitic skin infestation in which mite infestation, epidermal barrier disruption, secondary bacterial infection, and local inflammation collectively contribute to disease burden. This study investigated whether disulfiram, a component of a fixed-dose benzyl benzoate formulation, may provide local biological activity relevant to scabies-associated complications. Methods: Ex vivo permeation of the formulation was assessed in dermatomed porcine skin, with disulfiram retention in the stratum corneum and dermatomed skin measured against minimum inhibitory concentrations (MICs) for Staphylococcus aureus and Streptococcus pyogenes. Cytotoxicity of the formulation was evaluated in HEK001 keratinocytes across tested concentrations. In vitro antibacterial activity of disulfiram was tested against both Gram-positive species. Transcriptomic profiling was performed on keratinocytes exposed to the formulation. Results: Benzyl benzoate permeation was measurable in the ex vivo model, whereas disulfiram was not detected in the receptor phase under the experimental conditions. Disulfiram was retained in the stratum corneum and dermatomed skin at concentrations exceeding the MICs observed against S. aureus and S. pyogenes. The formulation was not cytotoxic in HEK001 keratinocytes at any tested concentration. Disulfiram showed in vitro antibacterial activity against both Gram-positive species. Transcriptomic profiling identified differential expression of genes involved in oxidative stress responses, detoxification, glutathione metabolism, innate immune signaling, and inflammatory mediator regulation. Conclusions: These findings support a mechanistic rationale for disulfiram as a locally retained component with potential therapeutic relevance to bacterial infection and keratinocyte inflammation in scabies.