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

Abstract

Objectives: To report the management of three consecutive patients with relapsing Staphylococcus aureus 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. Methods: Each case was discussed individually in our reference center and with the French National Agency (ANSM). The lytic activity of three phages targeting S. aureus , 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 × 10 10 PFU/ml for each phage) as “magistral” preparation (final dilution 1 × 10 9 PFU/ml), which was administered by the surgeon directly into the joint, after the DAIR procedure and joint closure (PhagoDAIR procedure). Results: 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. Conclusions: The PhagoDAIR procedure has the potential to be used as salvage for patients with relapsing S. aureus 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.

Successful Treatment of a Recalcitrant Staphylococcus epidermidis Prosthetic Knee Infection with Intraoperative Bacteriophage Therapy

“…However, her clinical improvement, previous lack of improvement with long term oral doxycycline therapy and the changes that occurred with respect to her pancytopenia are highly suggestive of cure. This is a limitation similar to other cases that did not have any severe underlying comorbidities but were continued on chronic suppression therapy and were deemed to have successful treatments [ 6 , 26 ].…”

“…Rather, eradication of her infection was paramount to then be able to improve her aplastic anemia with chemotherapy to prolong her life. Consequently, the patient consented to receive experimental adjuvant bacteriophage therapy to be used with DAIR to help eradicate the deep-seated biofilm infection as have occurred in other case reports [ 3 , 6 , 7 , 8 ].…”

“…Bacteriophage therapy has been used as an adjuvant therapeutic with conventional surgical and antibiotic therapies in several compassionate use cases to cure recalcitrant PJIs and orthopedic hardware infections [ 3 , 6 , 7 , 8 ]. The antibiofilm activity of bacteriophages and ability to kill metabolically inactive biofilm bacteria make this a potentially attractive adjuvant treatment in PJIs [ 9 , 10 ].…”

ε2-Phages Are Naturally Bred and Have a Vastly Improved Host Range in Staphylococcus aureus over Wild Type Phages

“…Even if plaques are formed on a given strain, in suspension, the bacteria may grow faster than the phages lyse them even at a starting MOI of 10. Currently, the suitability of individual phages for human phage therapy is mostly determined solely based on plaquing assays (“phagogram”) [ 54 , 55 , 56 , 57 , 58 ]. However, if the ability to form plaques does not indicate that the phage is able to control growth or even reduce the bacterial population, a phagogram by plaquing may not be the appropriate sole predictor for therapeutic success.…”

Case Report: Arthroscopic “Debridement Antibiotics and Implant Retention” With Local Injection of Personalized Phage Therapy to Salvage a Relapsing Pseudomonas Aeruginosa Prosthetic Knee Infection

“…The patient signed a written consent, explaining the procedure and the risk/benefit ratio. Hospital pharmacist mixed extemporaneously the active phages [initial concentrations 1 ml of 1 × 10 ( 5 ) PFU/ml for each phage] to obtain a cocktail of phages in a suspension form [final concentration of 1 × 10 ( 6 ) PFU/ml for both phages]. Conventional arthroscopy was performed ( Figure 1E ) using anteromedial and anterolateral entry points and washing of joint with saline.…”