"Debridement PhagE AnTibiotics for PJI"

Plain-language summary

Total joint replacement (TJR) has revolutionized care provided for patients suffering from disabling joint pain. Unfortunately, periprosthetic joint infection (PJI) remains a devastating complication and the leading cause of failure after TJR. Current standard treatment for PJI requires multiple surgical revisions of the infected prosthesis in combination with a prolonged course of systemic antibiotic therapy. Debridement Antibiotic and Implant Retention (DAIR) procedure is one of the surgical options that is routinely used to manage PJI, due to its lower risk of morbidity and surgical cost. DAIR is often used for patients who present with an acute PJI or who cannot tolerate a complex implant revision. However, the overall success rate for DAIR is ranging between 60-70%. DAIR failures are often attributed to the residual infection and biofilm burden left behind on the retained implant surface, which cannot be targeted effectively with post-operative systemic antibiotics. Therefore, research has been ongoing to identify non-surgical multidrug resistance (MDR) treatment adjuncts that can synergize the therapeutic effects of antibiotics in PJI care. Numerous preclinical bone and joint infection models have clearly demonstrated such therapeutic benefits using bacteriophages (phages). Phages target bacterial cells and breakdown biofilm that it forms on the implant surface. Each bacterial strain tends to have a particular phage that is susceptible to that bacterial strain. Due to this phage specificity and the fact that bacteria can still develop resistance against a single phage, the concept of using a phage cocktail (mixture of 2 or more phage candidates) has been the preferred treatment approach for applying phage therapy. Using a phage cocktail provides a broader spectrum of bacterial strain coverage and makes it harder for the bacteria to develop resistance. Published literature has considered phage therapy to be safe for direct administration at the infection site with minimal adverse events provided that the phage preparation administered meets Good Manufacturing Practice (GMP). The DePHEAT PJI trail, is a prospective, single center, 1:1 non-blinded feasibility randomized controlled trial (RCT) that aims to assess the safety and the effectiveness of the experimental phage therapy cocktails for patients with hip or knee PJI caused by either Staphylococcus (S.) aureus or Pseudomonas (P.) aeruginosa and comparing it to standardized therapy. The investigator hypothesizes that this pilot RCT will help evaluate the practicality and potential risks associated with adding phage therapy to the conventional standard of care treatment plan. This will initiate the development of a necessary infrastructure for future phage trials and programs that expand our understanding on the benefits of using phage therapy for acute PJI.

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