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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 × 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). 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.

SUBMITTER: Ferry T

PROVIDER: S-EPMC7701306 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Ferry Tristan T Kolenda Camille C Batailler Cécile C Gustave Claude-Alexandre CA Lustig Sébastien S Malatray Matthieu M Fevre Cindy C Josse Jérôme J Petitjean Charlotte C Chidiac Christian C Leboucher Gilles G Laurent Frédéric F

Frontiers in medicine 20201116

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 targe ...[more]

PMID: 33304911

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Project description:BackgroundProsthetic joint infection (PJI) is a potentially limb-threatening complication of total knee arthroplasty. Phage therapy is a promising strategy to manage such infections including those involving antibiotic-resistant microbes, and to target microbial biofilms. Experience with phage therapy for infections associated with retained hardware is limited. A 62-year-old diabetic man with a history of right total knee arthroplasty 11 years prior who had suffered multiple episodes of prosthetic knee infection despite numerous surgeries and prolonged courses of antibiotics, with progressive clinical worsening and development of severe allergies to antibiotics, had been offered limb amputation for persistent right prosthetic knee infection due to Klebsiella pneumoniae complex. Intravenous phage therapy was initiated as a limb-salvaging intervention.MethodsThe patient received 40 intravenous doses of a single phage (KpJH46Φ2) targeting his bacterial isolate, alongside continued minocycline (which he had been receiving when he developed increasing pain, swelling, and erythema prior to initiation of phage therapy). Serial cytokine and biomarker measurements were performed before, during, and after treatment. The in vitro anti-biofilm activity of KpJH46Φ2, minocycline and the combination thereof was evaluated against a preformed biofilm of the patient's isolate and determined by safranin staining.ResultsPhage therapy resulted in resolution of local symptoms and signs of infection and recovery of function. The patient did not experience treatment-related adverse effects and remained asymptomatic 34 weeks after completing treatment while still receiving minocycline. A trend in biofilm biomass reduction was noted 22 hours after exposure to KpJH46Φ2 (P = .063). The addition of phage was associated with a satisfactory outcome in this case of intractable biofilm-associated prosthetic knee infection. Pending further studies to assess its efficacy and safety, phage therapy holds promise for treatment of device-associated infections.

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

Publications

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

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