Application of Phage Therapy in a Case of a Chronic Hip-Prosthetic Joint Infection due toPseudomonas aeruginosa: An Italian Real-Life Experience andIn VitroAnalysis

Abstract

Prosthetic joint infection (PJI) caused by Pseudomonas aeruginosa represents a severe complication in orthopaedic surgery. We report the case of a patient with chronic PJI from P. aeruginosa successfully treated with personalised phage therapy (PT) in combination with meropenem. A 62-year-old woman was affected by a chronic right hip prosthesis infection since 2016 caused by P. aeruginosa. The patient was treated with phage Pa53 (I day 10 ml q8h, then 5 ml q8h via joint drainage for two weeks) in association with meropenem (2gr q12h iv) after a surgical procedure. A two-year clinical follow-up was performed. An in vitro bactericidal assay of the phage alone and in combination with meropenem against a 24h-old biofilm of bacterial isolate was also carried out. No severe adverse events were observed during PT. Two years after suspension there were no clinical signs of infection relapse, and a marked leukocyte scan showed no pathological uptake areas. In vitro studies showed that the minimum biofilm eradicating concentration of meropenem was 8 µg/ml. No biofilm eradication was observed at 24h incubation with phages alone (10⁸ PFU/ml). However, the addition of meropenem at sub-eradicating concentration (1µg/ml) to phages at lower titer (10³ PFU/ml) resulted in a synergistic eradication after 24h incubation. Personalized PT, in combination with meropenem, was found to be safe and effective in eradicating P. aeruginosa infection. These data encourage the development of personalized clinical studies aimed at evaluating the efficacy of PT as an adjunct to antibiotic therapy for chronic persistent infections.