USE OF BACTERIOPHAGE THERAPY AS SALVAGE TREATMENT FOR CHRONIC STAPHYLOCOCCUS AUREUS KNEE PROSTHETIC JOINT INFECTION

Aim To report the first UK case of bacteriophage (phage) therapy used alongside Debridement, Antibiotics, and Implant Retention (DAIR) for chronic Staphylococcus aureus knee prosthetic joint infection (PJI). Method An 81-year-old male with a history of ischaemic heart disease with residual mural thrombus, asthma and a left primary knee replacement 32 years prior which was revised to a mega-C distal femoral endoprosthesis in 2019 due to femoral loosening. One year later, the patient developed Staphylococcus aureus PJI with discharging sinuses. A two-stage revision was contraindicated due to anaesthetic risk and he declined amputation. He underwent a DAIR in 2021, arthroscopic washout in 2022 and drainage of a posterior abscess in 2023. Long-term suppression with doxycycline and co-trimoxazole failed to control symptoms and he continued to experience three persistently discharging sinuses. Suppression options were significantly limited due to multiple antibiotic allergies and intolerances (clindamycin, rifampicin, dalbavancin and penicillin) making effective long-term medical management unfeasible. In October 2023, his case was referred to the UK Clinical Phage Network for Bone and Joint Infection and following MDT review, the patient was selected for salvage phage therapy with DAIR to control persistent sinus output. Results Phage ISP (10 9 PFU/mL) was selected following susceptibility and phage-antibiotic synergy testing at Queen Astrid Military Hospital, Belgium. In October 2024, after local hospital and regulatory import approvals, 10 9 PFU/ml of phage was administered intra-articularly during DAIR with local antibiotic delivery of daptomycin and meropenem via a local hydrogel carrier (DAC). Systemic intravenous daptomycin and meropenem were initiated after deep tissue sampling . S. aureus was grown in 5/7 samples with multiple colonial variants identified. The patient was switched to long-term oral cefalexin and azithromycin. He experienced one episode of fever 48 hours post-operatively, which resolved spontaneously. Two further ultrasound-guided intra-articular injections of phages (10 9 PFU/ml) were administered on days D7 and D14, with no adverse events. All sinuses closed initially; two later reopened within 4 weeks and discharged intermittently. At 3 months, joint aspiration cultures (whilst on antibiotics) were negative. At 6 months, the patient reported reduced leg and knee swelling but persistent drainage from 2 sinuses. Conclusions This case demonstrates the feasibility of delivering phage therapy in a UK setting with the support of a Clinical Phage Network, despite a 13-month delay. Partial symptom control was achieved, though S. aureus colonial variants may have contributed to reduced treatment response and further evaluation for phage resistance is in progress.