A feasibility study for personalized phage therapy against drug-resistant bacteria in Japan

Introduction: Personalized phage therapy is used in Europe and the United States to treat intractable infections caused by drug-resistant bacteria. This pilot study aimed to acquire feasibility data for clinical trials of individualized phage therapy in Japan. Methods: An observational study was conducted from August 2023 to September 2024 in adults with drug-resistant bacterial infections and treatment failure or recurrence/relapse following antimicrobial therapy. Phages with activity against the detected bacteria were then identified from the environment and an existing phage library. Results: Thirty patients with drug-resistant bacterial infections were enrolled. Of these, six (20 %) died within 30 days of detection. The most commonly detected bacteria were methicillin-resistant Staphylococcus aureus (MRSA) (n = 10, 33.3 %) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) (n = 5, 16.7 %). The most common nontuberculous mycobacterium (NTM) was Mycobacterium avium (n = 4, 13.3 %), followed by Mycobacterium abscessus (n = 2, 6.7 %). In terms of infection types, respiratory tract infections were the most common (n = 13, 43.3 %), followed by bone and joint infections (n = 6, 20 %) and skin and soft tissue infections (n = 6, 20 %). Phages with a titer of 10⁸ PFU/ml or higher could be prepared for 26 out of 30 strains (86.7 %). Phages against CRPA were more readily identified from the environment than for MRSA and NTM. A phage against CRPA was purified to a lipopolysaccharide concentration of 0.023 EU/10⁸ PFU. Conclusion: Personalized phages can be prepared for intractable infections caused by drug-resistant bacteria. These results support the conduct of clinical trials to implement personalized phage therapy in Japan.