Periprosthetic Joint Infection (PJI)

Patients with an infected knee replacement will receive their standard of care surgical treatment of the infection, with and without additional ultrasound microbubble treatment (randomly divided 50/50 in the active and control groups). Subjects in the active group will receive a local bolus injection of antibiotics and ultrasound-active microbubbles within 24 hours of their revision surgery. The fundamental hypothesis is that a decrease in re-infection rates of at least 24% can be achieved in the active group relative to controls.

This is a Phase 1/2, randomized, controlled, open-label, proof-of-concept study to evaluate the safety and tolerability, local and systemic PK profiles of TNP-2092 administered via IA injection on the basis of vancomycin IV and oral antibiotics therapy in participants with early (within 1 month of TKA) or acute hematogenous (within 3 weeks of infectious symptoms) PJI requiring or not requiring DAIR therapy after TKA, or requiring long-term antibiotic suppression therapy for PJI (including PJI occurring after various joint replacements and revision surgeries).

With the progressive ageing of the population, a significant increase in the incidence of skeletal fractures-particularly of the proximal femur-as well as degenerative conditions such as osteoarthritis has been observed, for which joint arthroplasty represents the treatment of choice. However, this procedure is not free from complications; beyond technical and mechanical issues related to potential implant malpositioning, one of the most feared is periprosthetic joint infection (PJI), which poses a major challenge in terms of clinical management and prognostic impact. Therapeutic strategies for PJI range from debridement with retention of the implant and exchange of modular components (DAIR/DAPRI) to complete implant removal with insertion of an articulating spacer, often followed by a subsequent reimplantation procedure. These approaches require prolonged antibiotic regimens, potentially exerting a negative effect on renal function, particularly in cases of extended exposure to nephrotoxic agents. Despite the clinical relevance of this issue, the current literature still provides limited evidence regarding the identification of inexpensive and readily available biomarkers capable of predicting treatment outcomes in PJI, especially in patients undergoing spacer implantation followed by reimplantation. Recent literature has increasingly explored the use of biomarkers such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic inflammation response index (SIRI), and others to characterize inflammatory and nutritional status, and to investigate possible associations between these markers and the outcomes of selected surgical procedures. The availability of predictive markers could optimize therapeutic management by reducing the risk of infection recurrence and improving postoperative risk stratification.

The goal of this observational study is to measure the diagnostic accuracy of the Multiplex PCR technique in identifying pathogens during the diagnostic stage of resolving pre-implantation infection, in the context of treatment according to two-stage protocol for PJIs. This evaluation will be conducted by comparing the results obtained by Multiplex PCR with those derived from standard culture examination.