Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy · 2025
A feasibility study for personalized phage therapy against drug-resistant bacteria in Japan.
СтатьяНаблюдательное исследованиеНазвание и аннотация: Перевод в очереди
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Hayakawa Kayoko, Kiga Kotaro, Ojima Shinjiro, Chihara Kotaro, Tamura Azumi, Yamashita Wakana, Nakamura Tomohiro, Azam Aa Haeruman, Nie Wenhan, Sato Yuta, Sakai Jun, Kondo Kohei, Takahashi Yoshimasa, Watashi Koichi, Saito Sho, Moriyama Yuki, Kurokawa Masami, Mezaki Kazuhisa, Ohashi Hirotake, Ohashi Yasukata, Nishimura Takahiro, Shinohara Koh, Yamagishi Yoshiaki, Doi Yohei, Ohmagari Norio
Аннотация
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.
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.