Treating orthopedic implant-associated infections, especially those caused by Staphylococcus aureus (S. aureus), remains a significant challenge. S. aureus has the ability to invade host cells, enabling it to evade both antibiotics and immune responses during infection, which may result in clinical treatment failures. Therefore, it is critical to identify the host cell type of implant-associated intracellular S. aureus infections and to develop a strategy for highly targeted delivery of antibiotics to the host cells. Introduced an antibody-antibiotic conjugate (AAC) for the targeted elimination of intracellular S. aureus. The AAC comprises of a human monoclonal antibody (M0662) directly recognizes the surface antigen of S. aureus, Staphylococcus protein A, which is conjugated with vancomycin through cathepsin-sensitive linkers that are cleavable in the proteolytic environment of the intracellular phagolysosome. AAC, vancomycin and vancomycin combined with AAC were used in vitro intracellular infection and mice implant infection models. We then tested the effect of AAC in vivo and in vivo by fluorescence imaging, in vivo imaging, bacterial quantitative analysis and bacterial biofilm imaging. In vitro, it was observed that AAC captured extracellular S. aureus and co-entered the cells, and subsequently released vancomycin to induce rapid elimination of intracellular S. aureus. In the implant infection model, AAC significantly improved the bactericidal effect of vancomycin. Scanning electron microscopy showed that the application of AAC effectively blocked the formation of bacterial biofilm. Further histochemical and micro-CT analysis showed AAC significantly reduced the level of bone marrow density (BMD) and bone volume fraction (BV/TV) reduction caused by bacterial infection in the distal femur of mice compared to vancomycin treatment alone. The application of AAC in an implant infection model showed that it significantly improved the bactericidal effects of vancomycin and effectively blocked the formation of bacterial biofilms, without apparent toxicity to the host.

Background: Diagnosis of periprosthetic joint infection (PJI), especially chronic PJI, is very confusing and challenging. The value of C-reactive protein (CRP) in infectious diseases has been recognized, but the diagnostic value of CRP in chronic PJI is unknown. Our aim was to investigate the diagnostic value of synovial CRP in chronic PJI and to explore the role of combined serum and synovial CRP in distinguishing chronic PJI from aseptic failure after knee and hip arthroplasties. Methods: We prospectively enrolled patients scheduled to have a revision surgery for chronic PJI or aseptic loosening from January 2019 to December 2020, in which synovial CRP was additionally measured along with routine preoperative diagnostic serum ((ESR, CRP) and synovial (PMN%) biomarkers. The receiver operating characteristic (ROC) curves and area under the curve (AUC) were analyzed for each biomarker to determine diagnostic efficacy. Results: There were no statistically significant differences between the infection (n = 39) and aseptic (n = 58) groups, including 61 hips and 36 knees. The synovial CRP levels were significantly higher in the infection group than in the aseptic group (median: 9.93 mg/l vs 3.58 mg/l; p < .001). The optimal cut-off value for detecting chronic PJI of Synovial fluid (SF) CRP was of 7.26 mg/l with a sensitivity of 84.62%, a specificity of 93.10%. The combined model I (Serum CRP > 10.2 mg/l OR SF CRP > 7.26 mg/l) had a negative predictive value (NPV) of 96.67%, and a sensitivity of 97.44%. The combined model II (Serum CRP > 10.2 mg/l AND Synovial CRP > 7.26 mg/l) led to a specificity of 1, and a positive predictive value (PPV) of 1. Conclusions: The present study demonstrated that the combination of serum and synovial CRP can be used as an adjunct to the diagnosis of chronic PJI.

Periprosthetic joint infection (PJI) is a catastrophic complication following joint replacement surgery, posing significant challenges to orthopedic surgeons. Due to the lack of a definitive diagnostic gold standard, timely treatment initiation is problematic, resulting in substantial economic burdens on patients and society. In this review, we thoroughly analyze the complexities of PJI and emphasize the importance of accurate diagnosis and effective treatment. The article specifically focuses on the advancements in diagnostic techniques, ranging from traditional pathogen culture to advanced molecular diagnostics, and discusses their role in enhancing diagnostic accuracy. Additionally, we review the latest surgical management strategies, including everything from debridement to revision surgeries. Our summary aims to provide practical information for the diagnosis and treatment of PJI and encourages further research to improve diagnostic accuracy and treatment outcomes.

Background: The diagnosis of periprosthetic joint infection (PJI) remains a challenge in clinical practice. Many novel serum and joint fluid biomarkers have important implications for the diagnosis of PJI. The presented study evaluated the value of joint fluid interleukin-6 (IL-6) combined with the neutral polymorphonuclear leukocyte (PMN%) ratio for chronic PJI diagnosis after arthroplasty. Materials and methods: Sixty patients with chronic PJI or aseptic failure who underwent hip or knee revision from January 2018 to January 2020 in our department were included in this retrospective study. According to the 2013 MSIS diagnostic criteria, the 60 patients were divided into a PJI group and a non-PJI group (30 patients per group). We collected the joint fluid before surgery and determined the level of IL-6 and the PMN% by ELISA, and the differences between the two groups were compared. The diagnostic efficacy of joint fluid IL-6 combined with PMN% in chronic PJI was analyzed using a receiver operating characteristic curve (ROC curve). Results: The diagnosis of PJI using joint fluid IL-6 combined with PMN% presented an area under the curve of 0.983, which was more accurate than the areas under the curve for diagnosis using IL-6 and PMN% individually (0.901 and 0.914, respectively). The optimal threshold values for IL-6 and PMN% were 662.50 pg/ml and 51.09%, respectively. Their sensitivity and specificity were 96.67% and 93.33%, respectively. The accuracy of the diagnosis of PJI was 95.00%. Conclusions: Joint fluid IL-6 combined with PMN% can be used as an auxiliary method to detect chronic infection around the prosthesis after hip/knee arthroplasty. Level of evidence: Patients who underwent hip/knee revision at the First Hospital of Chongqing Medical University for periprosthetic infection or aseptic failure of the prosthesis after hip/knee arthroplasty from January 2018 to January 2020 were included. Trial registration This study was approved by the ethics committee of the First Hospital of Chongqing Medical University on September 26, 2018 (local ethics committee number: 20187101) and registered with the China Clinical Trials Registry (registration number: ChiCTR1800020440) with an approval date of December 29, 2018.