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Personalized bacteriophage therapy for chronic biliary tract Pseudomonas aeruginosa infections

摘要Biliary tract infections(BTIs)present a significant therapeutic challenge,particularly in the face of increasing antimicro-bial 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 treat-ment 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 dou-ble-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.Howev-er,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.

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作者单位 Department of Infectious Diseases,Zhongshan Hospital Fudan University,Shanghai,China;Shanghai Institute of Infectious Disease and Biosecurity,Fudan University,Shanghai,China;Fudan University Phage Institute,Zhongshan Hospital Fudan University,Shanghai,China [1] Shanghai Institute of Phage,Shanghai Public Health Clinical Center,Fudan University,Shanghai,China [2] Department of Microbiology,College of Basic Medical Sciences,Key Laboratory of Microbial Engineering Under the Educational Committee in Chongqing,Army Medical University,Chongqing,China [3] Department of Infectious Diseases,Zhongshan Hospital Fudan University,Shanghai,China [4] Shanghai Institute of Phage,Shanghai Public Health Clinical Center,Fudan University,Shanghai,China;CreatiPhage Biotechnology,Co.,Ltd.,Shanghai,China [5] Fudan University Phage Institute,Zhongshan Hospital Fudan University,Shanghai,China;Shanghai Institute of Phage,Shanghai Public Health Clinical Center,Fudan University,Shanghai,China;CreatiPhage Biotechnology,Co.,Ltd.,Shanghai,China [6] Department of Laboratory Medicine,Zhongshan Hospital Fudan University,Shanghai,China [7] Department of Gastroenterology,Zhongshan Hospital Fudan University,Shanghai,China [8] Department of Interventional Radiology,Zhongshan Hospital Fudan University,Shanghai,China [9] Department of Microbial Physiological & Metabolic Engineering,State Key Laboratory of Microbial Diversity and Innovative Utilization,Chinese Academy of Sciences,Beijing,China [10] Fudan University Phage Institute,Zhongshan Hospital Fudan University,Shanghai,China;Shanghai Medical College,Fudan University,Shanghai,China;Shanghai Key Laboratory of Organ Transplantation,Department of Kidney Transplantation,Zhongshan Hospital Fudan University,Shanghai,China [11]
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DOI 10.1016/j.hlife.2025.03.004
发布时间 2025-08-11(万方平台首次上网日期,不代表论文的发表时间)
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