Dosage, Efficacy, and Safety of Intra-articular Vancomycin for Prophylaxis of Periprosthetic Joint Infection Caused by Methicillin-Resistant Staphylococcus aureus after Total Knee Arthroplasty in a Rat Model

Although intra-articular vancomycin powder (VP) is sometimes applied before the closure of the incision to prevent periprosthetic joint infection (PJI) after joint replacement, the dosage, efficacy, and safety remain controversial. This study aimed to explore the dosage, efficacy, and safety of intra-articular VP in the prophylaxis of infection after total knee arthroplasty (TKA) in a rat model. Sixty male rats were randomly divided into five groups after receiving TKA: control (no antibiotics); systemic vancomycin (SV) (intraperitoneal injection, 88 mg/kg of body weight, equal to 1 g in a patient weighing 70 kg); and VP0.5, VP1.0, and VP2.0 (44 mg/kg, 88 mg/ kg and 176 mg/kg, respectively; intra-articular). All animals were inoculated in the knee with methicillin-resistant S. aureus (MRSA). General status, serum biomarkers, radiology, microbiological assay, and histopathological tests were assessed within 14 days postoperation. Compared with the control and SV groups, bacterial counts, knee width, tissue inflammation, and osteolysis were reduced in the VP0.5, VP1.0, and VP2.0 groups, without notable body weight loss and incision complications. Among all the VP groups, VP1.0 and VP2.0 groups presented superior outcomes with regard to knee width and tissue inflammation than the VP0.5 group. Microbial culture indicated that no MRSA survived in the knee of VP1.0 and VP2.0 groups, while bacteria growth was observed in the VP0.5 group. No obvious changes in the structure and functional biomarkers of liver and kidney were observed in either the SV or VP groups. Therefore, intra-articular vancomycin powder at a dosage from 88 mg/kg to 176 mg/kg may be effective and safe in preventing P11 induced by methicillin-resistant S. aureus in the rat TKA model.