Phage Therapy as Adjuvant to Conservative Surgery and Antibiotics to Salvage Patients With Relapsing S. aureus Prosthetic Knee Infection

Abstract

<b>Objectives:</b> To report the management of three consecutive patients with relapsing <i>Staphylococcus aureus</i> prosthetic knee infection (PKI) for whom explantation was not feasible who received a phage therapy during a "Debridement Antibiotics and Implant Retention" (DAIR) procedure followed by suppressive antimicrobial therapy. <b>Methods:</b> Each case was discussed individually in our reference center and with the French National Agency (ANSM). The lytic activity of three phages targeting <i>S. aureus</i>, which was produced with a controlled and reproducible process, was assessed before surgery (phagogram). A hospital pharmacist extemporaneously assembled the phage cocktail (1 ml of 1 × 10¹⁰ PFU/ml for each phage) as "magistral" preparation (final dilution 1 × 10⁹ PFU/ml), which was administered by the surgeon directly into the joint, after the DAIR procedure and joint closure (PhagoDAIR procedure). <b>Results:</b> Three elderly patients were treated with the PhagoDAIR procedure. Phagograms revealed a high susceptibility to at least two of the three phages. During surgery, all patients had poor local conditions including pus in contact to the implant. After a prolonged follow-up, mild discharge of synovial fluid persisted in two patients, for whom a subsequent DAIR was performed showing only mild synovial inflammation without bacterial persistence or super-infection. The outcome was finally favorable with a significant and impressive clinical improvement of the function. <b>Conclusions:</b> The PhagoDAIR procedure has the potential to be used as salvage for patients with relapsing <i>S. aureus</i> PKI, in combination with suppressive antibiotics to avoid considerable loss of function. This report provides preliminary data supporting the setup of a prospective multicentric clinical trial.