80. Combined Regimen of Minimally Invasive Negative Pressure Wound Therapy With Instillation and Antibiotic Therapy Resolved Infection at Skin-implant Interfaces of Infected Percutaneous Osseointegrated Devices

PURPOSE: Percutaneous osseointegrated (OI) prosthetics are superior alternatives to socket-type prosthetics. Unfortunately, the healing cascades at the percutaneous exit site can create a potential sinus tract, serving as a nidus and heightening the risk of infection. Literature indicates an 18-70% infection rate with percutaneous OI devices, stressing the need for solutions that do not increase the risk of developing antibiotic-resistant strains. Negative pressure wound therapy with instillation (NPWTi) has demonstrated efficacy in treating chronic and hard-to-heal wounds. Hence, it was considered a potential treatment option for combating infection around percutaneous devices. It was hypothesized that a NPWTi treatment regimen would be non-inferior to the current standard of care for local skin-implant interface infection, a systemic antibiotic therapy. METHODS: Following necessary institutional approvals, 60 hairless rats were randomly assigned into six groups (n = 10/group): positive control, negative control, intraperitoneal (IP) cefazolin injection (antibiotics), NPWTi, NPWT, and combination therapy (antibiotics + NPWTi). A transcutaneous device fabricated from medical-grade titanium alloy was subdermally placed on the back of each rat. After a four-week healing phase, 50 rats were inoculated with 108 colonies of Staphylococcus aureus (strain 25923, ATCC), followed by a one-week interval for infection development. Forty infected rats received five days of interventions with either cefazolin IP injection (n=10), NPWTi with local cefazolin (n=10), NPWT (n=10), or combination therapy (n=10), while 10 animals remained untreated (positive control). Treated animals were then euthanized one week post-treatment. The negative control group (n=10) animals were euthanized 7 weeks post-implantation without bacterial inoculation or treatment. Following euthanasia, interfacial tissues were collected using sterile collection procedures for bacterial quantification. The tissues, including implants, were harvested and processed for histology. The total number of bacteria was calculated from a known tissue and expressed as an average number ± 95%CI. The t-tests were used to assess noninferiority in responses between the groups. RESULTS: Overall, our data showed that combination therapy reduced bacteria content on all tissue samples (skin and underlying fat tissue) significantly, confirming the hypothesis. Histological data further supported bacterial count data. Additionally, the immunohistochemical assay showed that interface tissues infiltrated with neutrophils within the skin tissue taken from positive control, antibiotic therapy, and NPWT. The H&E stained sections of combination therapy resembled the negative control samples. CONCLUSION: Based on the data, NPWTi could be vital in treating superficially infected percutaneous OI devices. Although bacterial count within the skin tissue was lowered when using NPWTi treatment alone, this treatment was ineffective in treating the deep tissue (fat) infection. This observation suggested NPWTi alone could not resolve deep tissue infection. The data further suggest that combined therapies of NPWTi with different lower doses of antibiotics are worth exploring to address both superficial and deep tissue infections.