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

Abstract

Bacteriophages are viruses that specifically target bacteria. They are considered to have a high potential in patients with prosthetic joint infection (PJI), as they have a synergistic anti-biofilm activity with antibiotics. We report here the case of an 88-year-old man (63 kg) with relapsing Pseudomonas aeruginosa prosthetic knee infection. The patient had severe alteration of the general status and was bedridden with congestive heart failure. As prosthesis explantation and/or exchange was not feasible, we proposed to this patient the use of phage therapy to try to control the disease in accordance with the local ethics committee and the French National Agency for Medicines and Health Products Safety (ANSM). Three phages, targeting P. aeruginosa, were selected based on their lytic activity on the patient's strain (phagogram). Hospital pharmacist mixed extemporaneously the active phages (initial concentration 1 ml of 1 × 10¹⁰ PFU/ml for each phage) to obtain a cocktail of phages in a suspension form (final dilution 1 × 10⁹ PFU/ml for both phages). Conventional arthroscopy was performed and 30 cc of the magistral preparation was injected through the arthroscope (PhagoDAIR procedure). The patient received intravenous ceftazidime and then oral ciprofloxacin as suppressive antimicrobial therapy. Under this treatment, the patient rapidly improved with disappearance of signs of heart failure and pain of the left knee. During the follow-up of 1 year, the local status of the left knee was normal, and its motion and walking were unpainful. The present case suggests that the PhagoDAIR procedure by arthroscopy has the potential to be used as salvage therapy for patients with P. aeruginosa relapsing PJI, in combination with suppressive antimicrobial therapy. A Phase II clinical study deserves to be performed to confirm this hypothesis.

Keywords: P aeruginosa; bacteriophages; phage therapy; phagotherapy; prosthetic-joint infection.

Figure 1

(A) Left knee joint effusion due to relapsing P. aeruginosa prosthesis knee infection; (B) X-ray showing no prosthesis loosening. The susceptibility of the patient's strain to the bacteriophages PP1450, PP1777, and PP1792 (phagogram) was performed using two complementary techniques: (C) For the kinetic assay, phages were incubated at a theorical multiplicity of infection (MOI, ratio of phages/bacteria) equal to 100 with the patient's strain. PP1450 was able to inhibit the bacterial growth (gray full line); PP1792 delayed the bacterial growth (gray dotted line) and PP1777 had no impact (gray dashed line). (D) For the plaque assay, titers obtained with the patient's strain and the reference strain are determined to calculate the efficiency of plating score (EOP) score (the closer to 1 is the score, the more efficient the phage is). Phages PP1450 and PP1777 were active on the patient's strain with an EOP score of 2.0 × 10⁻⁵ and 4.0 × 10⁻⁶, respectively. Partial lysis without PFU were observed for PP1792 (considered to have a weak bactericidal or bacteriostatic activity in this assay). (E) Arthroscopic DAIR with administration of the phage cocktail at the end of the procedure through the arthroscope. (F) Ulceration of a subcutaneous nodule on the external side of the knee observed 2 months after the arthroscopy. (G) Finally, a favorable outcome under suppressive antimicrobial therapy.