BACKGROUND: In view of the ever-increasing representation of Staphylococcus spp. strains resistant to various antibiotics, the development of in vivo models for evaluation of novel antimicrobials is of utmost importance. METHODS: In this article, we describe the development of a fully immunocompetent porcine model of extensive skin and soft tissue damage suitable for testing topical antimicrobial agents that matches the real clinical situation. The model was developed in three consecutive stages with protocols for each stage amended based on the results of the previous one. RESULTS: In the final model, 10 excisions of the skin and underlying soft tissue were created in each pig under general anesthesia, with additional incisions to the fascia performed at the base of the defects and immediately inoculated with Staphylococcus aureus suspension. One pig was not inoculated and used as the negative control. Subsequently, the bandages were changed on Days 4, 8, 11, and 15. At these time points, a filter paper imprint technique (FPIT) was made from each wound for semi-quantitative microbiological evaluation. Tissue samples from the base of the wound together with the adjacent intact tissue of three randomly selected defects of each pig were taken for microbiological, histopathological, and molecular-biological examination. The infection with the inoculated S. aureus strains was sufficient during the whole experiment as confirmed by both FPIT and from tissue samples. The dynamics of the inflammatory markers and clinical signs of infection are also described. CONCLUSIONS: A successfully developed porcine model is suitable for in vivo testing of novel short-acting topical antimicrobial agents.

• Keywords
• Staphylococcus aureus, animal model, antimicrobial agents, porcine model, skin and soft‐tissue infection (SSTI), wound infection,
• MeSH
• Anti-Bacterial Agents * administration & dosage   therapeutic use   pharmacology   MeSH
• Administration, Topical MeSH
• Soft Tissue Infections * drug therapy   microbiology   MeSH
• Skin microbiology   pathology   MeSH
• Methicillin-Resistant Staphylococcus aureus * drug effects   MeSH
• Disease Models, Animal * MeSH
• Swine MeSH
• Staphylococcal Skin Infections * drug therapy   microbiology   MeSH
• Staphylococcal Infections * drug therapy   microbiology   MeSH
• Staphylococcus aureus * drug effects   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Bacterial Agents * MeSH

Wound dressings with silver have been shown to be cytotoxic in vitro. However, the extrapolation of this cytotoxicity to clinical settings is unclear. We applied dressings with various forms of silver on porcine skin ex vivo and investigated silver penetration and DNA damage. We assessed antimicrobial efficacy, cytotoxicity to skin cells, and immune response induced by the dressings. All dressings elevated the DNA damage marker γ-H2AX and the expression of stress-related genes in explanted skin relative to control. This corresponded with the amount of silver in the skin. The dressings reduced viability, induced oxidative stress and DNA damage in skin cells, and induced the production of pro-inflammatory IL-6 by monocytes. The oxidative burst and viability of activated neutrophils decreased. The amount of silver released into the culture medium varied among the dressings and correlated with in vitro toxicity. However, antimicrobial efficiencies did not correlate strongly with the amount of silver released from the dressings. Antimicrobial efficiency and toxicity are driven by the form of silver and the construction of dressings and not only by the silver concentration. The damaging effects of silver dressings in ex vivo skin highlight the importance of thorough in vivo investigation of silver dressing toxicity.

• MeSH
• Cell Line MeSH
• Wound Infection MeSH
• Skin chemistry   cytology   drug effects   MeSH
• Humans MeSH
• Bandages adverse effects   MeSH
• DNA Damage * MeSH
• Swine MeSH
• Silver toxicity   MeSH
• Tissue Culture Techniques MeSH
• Cell Survival drug effects   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Silver MeSH