Percutaneous osseointegrated implant technology provides a potential alternative to current socket prosthetics for individuals with limb loss. However, similar to other percutaneous devices, there remain concerns of periprosthetic infection. To understand this process of infection, bacterial isolates were collected and characterized from a sheep model of osseointegration. CSA-13, a novel cationic steroid antimicrobial, was used at the skin/implant interface in an attempt to reduce the rate of infection. Results indicated that in this application, normal flora and environmental organisms continued to colonize the skin/implant interface as well as cause infection in the presence of CSA-13. Two factors are believed to have contributed to this outcome: the delivery of CSA-13 and the lack of a skin seal at the skin/implant interface, which would create a biological barrier to infection.