Personalized bacteriophage therapy for chronic biliary tract Pseudomonas aeruginosa infections

Abstract

Biliary tract infections (BTIs) present a significant therapeutic challenge, particularly in the face of increasing antimicrobial resistance. Bacteriophages, viruses that target and destroy bacteria, offer the potential for treating severe bacterial infections, although their use in BTIs has been limited. We describe an 88-year-old female with a complex and recurrent BTI caused by multiple bacteria, including multidrug-resistant Pseudomonas aeruginosa. Despite treatment with various antibiotics and percutaneous transhepatic cholangiodrainage (PTCD), her condition did not improve. As a final measure, we implemented personalized phage therapy in combination with antibiotics. An initial 9-day antibiotic treatment combined with a P. aeruginosa phage cocktail administered via PTCD fluid resulted in significant symptom relief. However, phage-resistant pathogens emerged, exhibiting resistance to all 100 double-stranded DNA (dsDNA) phages in our library due to genetic mutations affecting lipopolysaccharides biosynthesis. A second round of therapy with a double-stranded RNA (dsRNA) phage, phiYY, which targets O-antigen deficient mutants, was subsequently administered. Although complete eradication of P. aeruginosa was not achieved, the patient's clinical symptoms were markedly improved. This case demonstrated the safety and efficacy of phage therapy in the treatment of BTIs and showcased the feasibility of employing dsRNA phages to combat the emergence of O-antigen-deficient bacterial mutants. However, it also underscores the considerable challenges in completely eradicating persistent P. aeruginosa infections, which may be attributed to bacterial heterogeneity, biofilm formation, and phage-resistant genetic mutations.