Timely bespoke phage-antibiotic combination to treat refractory Pseudomonas aeruginosa mediastinitis and vascular graft infection

Abstract

Abstract Biofilm-related vascular graft infections (VGIs) pose major therapeutic challenges due to persistent, antibiotic-resistant bacteria often residing in retained grafts. Phage therapy offers a promising alternative treatment strategy against biofilm-associated infections, though its use remains mostly ad hoc and typically considered a last-resort intervention. We report here the treatment of a refractory, fluoroquinolone non-susceptible Pseudomonas aeruginosa VGI using a systematically planned and synergistic phage-antibiotic combination approach. Adjunctive phage therapy led to radiological improvement, as seen by reduced 18F-FDG PET/CT tracer uptake around the graft. The patient was transitioned to oral fluoroquinolone suppression therapy with no recurrence of bacteremia to-date, after a year. Our workflow led to the selection of phages that sensitized Pseudomonas aeruginosa to killing by levofloxacin and piperacillin-tazobactam. We established that this phage-driven antibiotic sensitization was due to the ability of our phages to use the MexAB-OprM efflux pump as a receptor. We also showed that our phages had potent anti-biofilm activity. We advocate a systematic, multi-pronged management strategy for refractory VGIs, including early therapeutic drug monitoring (TDM), in vitro antibiotic combination testing (iACT), and timely adjunctive phage therapy. This case illustrates the utility of individualized, strategic approaches and highlights adjunctive phage therapy’s potential in treating complex biofilm-related infections.