Phage therapy in revision arthroplasty: State of the art and application protocols

TL;DR

This paper reviews the current state of phage therapy for treating joint infections after surgery, highlighting its potential and challenges.

Contribution

The study provides updated guidelines for phage therapy application in periprosthetic joint infections.

Findings

Phage therapy combined with antibiotics and surgery showed high success rates in elderly patients with knee or hip infections.

Phage therapy was well tolerated, with only mild adverse effects reported.

Clinical adoption is limited by regulatory barriers and lack of standardized protocols.

Abstract

Periprosthetic joint infections (PJI) pose significant clinical challenges due to biofilm formation and antibiotic resistance. Standard treatment often involves implant removal and prolonged antibiotic therapy. Novel strategies target intracellular pathogens and biofilm-associated bacteria, including liposomal antibiotics, antimicrobial peptides, and bacteriophage therapy. Bacteriophages offer specificity and minimal disruption to human microbiota but remain experimental in PJI. Combining phages with targeted antibiotics shows promising results in preclinical models, though further research is needed to confirm efficacy in human PJI and optimise delivery methods.

This study updates the current evidence on the use of bacteriophages for patients with PJI, proposing guidelines for their clinical application.

PubMed was searched for articles containing phage therapy in revision arthroplasty. No additional filters or time constraints were used. All eligible studies were accessed by hand.

A total of 39 studies (20 clinical, 19 reviews) on phage therapy for PJI were analysed, covering 56 patients. Of those, negative outcomes were only reported in five. Most studies involved elderly patients with periprosthetic infections of the knee or hip and showed high success rates when combined with antibiotics and surgery. Phage therapy was well tolerated, with only mild adverse effects, such as fever and reversible transaminitis, occurring predominantly with intravenous administration. Review articles reveal that despite promising outcomes, challenges remain, including a lack of standardisation, limited clinical data, and regulatory hurdles.

This study highlights the potential of phage therapy for PJI, emphasising its high specificity, ability to target antibiotic-resistant bacteria, and capacity to disrupt biofilms, and provides a guideline for its clinical administration. Clinical adoption, however, remains limited by regulatory barriers, lack of standardised protocols, and insufficient trial data. Key steps for implementation include establishing regulatory frameworks, developing academic–industrial partnerships and reference centres, and identifying indications supported by controlled trials. With these in place, phage therapy could become a promising adjunct in managing periprosthetic joint infections.

Video Abstract

Video Abstract

The online version contains supplementary material available at 10.1186/s42836-025-00355-6.

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