Invesigation of the effectiveness of antibiotic spacers with different doses in the model of periprosthetic infection in rats

Purpose: In the initial stage of prosthetic infection treatment, the prosthesis is removed and a spacer is applied. The spacer contains antibiotics, but the local release of this antibiotic is limited to 2-4 days. If infection control cannot be achieved in patients, it may be necessary to repeat the same surgical procedure. The aim of this study is to increase the concentration of antibiotics in the spacer to prolong the local release period and achieve faster infection control. Method: In this study, 30 Wistar albino rats were randomly divided into 3 groups of 10 each. A methicillin-resistant Staphylococcus aureus periprosthetic infection model was developed in all groups by placing an implant in the femoral intramedullary region after knee arthrotomy. After implant removal, washing, and debridement, the first group (control) received intramuscular vancomycin (88 mg/kg) and gentamicin (6 mg/kg); the second group received a low-dose antibiotic spacer (1 gram cement + 25 mg vancomycin); and the third group received a high-dose antibiotic spacer (1 gram cement + 75 mg vancomycin). Systemic antibiotic administration (88 mg/kg vancomycin + 6 mg/kg gentamicin) was continued in all groups until the 28nd day after the second surgical stage. On the 1st, 3rd, 7th, 14th, 28th, and 42nd days after the second surgical stage, blood samples were taken from all groups, and joint puncture samples were taken from the second and third groups. The level of vancomycin in plasma and joint puncture samples was determined by high-pressure liquid chromatography. Before proceeding to the second surgical stage, microbiological samples were taken from the joint and femoral medulla of each group. Euthanasia was performed on 5 rats from each group on the 28th and 42nd days under deep anesthesia. Sterile joint fluid and femoral medulla samples were taken and sent for microbiological analysis. Necropsy was performed, and the study was finished on the 42nd day. Femur sections obtained from all groups were histopathologically examined to score intramedullary acute and chronic inflammation, periosteal inflammation, and bone necrosis. Results: Microbiological and histopathological examinations performed on samples taken on the 28th day revealed bacterial growth in the first and second groups, while no growth occurred in the third group (p=0.001). On the 42nd day, bacterial growth was observed only in the first group (p=0.001). Plasma antibiotic concentrations were similar between groups on days 1, 3, 7, and 14, but higher in the third group on day 28 (p=0.004). Conclusions: It was determined that a spacer containing a high level of antibiotics was more effective than a spacer containing a normal level of antibiotics in terms of treatment duration and healing rate. The concentration of antibiotics applied with the spacer did not affect plasma antibiotic concentration and did not lead to systemic side effects. Keywords: Antibiotic loaded spacer; Bone cement; MRSA; Total knee arthroplasty, Vancomycin