Khatami Ameneh, Lin Ruby C Y, Petrovic-Fabijan Aleksandra, Alkalay-Oren Sivan, Almuzam Sulaiman, Britton Philip N, Brownstein Michael J, Dao Quang, Fackler Joe, Hazan Ronen, Horne Bri'Anna, Nir-Paz Ran, Iredell Jonathan R
Department of Infectious Diseases and Microbiology, The Children's Hospital at Westmead, Westmead, NSW, Australia.
Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
EMBO Mol Med. 2021 Sep 7;13(9):e13936. doi: 10.15252/emmm.202113936. Epub 2021 Aug 9.
Adjunctive phage therapy was used in an attempt to avoid catastrophic outcomes from extensive chronic Pseudomonas aeruginosa osteoarticular infection in a 7-year-old child. Monitoring of phage and bacterial kinetics allowed real-time phage dose adjustment, and along with markers of the human host response, indicated a significant therapeutic effect within two weeks of starting adjunctive phage therapy. These findings strongly suggested the release of bacterial cells or cell fragments into the bloodstream from deep bony infection sites early in treatment. This was associated with transient fever and local pain and with evidence of marked upregulation of innate immunity genes in the host transcriptome. Adaptive immune responses appeared to develop after a week of therapy and some immunomodulatory elements were also observed to be upregulated.
辅助噬菌体疗法被用于一名7岁儿童，试图避免因广泛慢性铜绿假单胞菌骨关节感染而导致灾难性后果。对噬菌体和细菌动力学的监测允许进行实时噬菌体剂量调整，并且与人类宿主反应的标志物一起，表明在开始辅助噬菌体治疗两周内有显著治疗效果。这些发现强烈提示在治疗早期，细菌细胞或细胞碎片从深部骨感染部位释放到血液中。这与短暂发热和局部疼痛相关，并且在宿主转录组中有证据表明先天免疫基因显著上调。适应性免疫反应似乎在治疗一周后出现，并且还观察到一些免疫调节元件上调。
