Bacteriophages in Hip and Knee Periprosthetic Joint Infections: A Promising Tool in the Era of Antibiotic Resistance

<b>Background</b>: Periprosthetic joint infections (PJIs) of the hip and knee are one of the most severe complications in arthroplasty, often requiring prolonged antibiotic therapy and multiple revision surgeries. The increasing prevalence of multidrug-resistant organisms and biofilm-associated PJIs has renewed interest in bacteriophage therapy as a targeted, adjunctive treatment option in refractory cases. This investigation systematically reviews and discusses the current evidence regarding the application, outcomes, and safety profile of bacteriophage therapy in the management of PJIs. <b>Methods</b>: This systematic review was conducted in accordance with the 2020 PRISMA statement. PubMed, Google Scholar, EMBASE, and Web of Science were accessed in August 2025. No time constraints were used for the search. All clinical studies investigating bacteriophage therapy for bacterial PJIs were considered for eligibility. <b>Results</b>: A total of 18 clinical studies, comprising 53 patients treated with bacteriophage therapy for PJI, were included. The mean follow-up was approximately 13.6 months. <i>Staphylococcus aureus</i> was the most frequent pathogen (18 cases); phage cocktails were used in 33 patients and monophage preparations in 9, all combined with suppressive antibiotic therapy. Persistent or resistant joint pain was reported in only two patients (3.8%), while signs of ongoing infection despite phage therapy were observed in four patients (7.5%). Adverse events following BT were inconsistently reported. <b>Conclusions</b>: Bacteriophage therapy shows promise as an adjunctive treatment for hip and knee PJIs, especially in refractory or multidrug-resistant cases. Current evidence is limited and methodologically weak, underscoring the need for well-designed clinical trials to clarify efficacy, safety, and optimal integration into existing orthopaedic infection protocols.