Two mycobacteriophages were administered intravenously to a male with treatment-refractory Mycobacterium abscessus pulmonary infection and severe cystic fibrosis lung disease. The phages were engineered to enhance their capacity to lyse M. abscessus and were selected specifically as the most effective against the subject’s bacterial isolate. In the setting of compassionate use, the evidence of phage-induced lysis was observed using molecular and metabolic assays combined with clinical assessments. M. abscessus isolates pre and post-phage treatment demonstrated genetic stability, with a general decline in diversity and no increased resistance to phage or antibiotics. The anti-phage neutralizing antibody titers to one phage increased with time but did not prevent clinical improvement throughout the course of treatment. The subject received lung transplantation on day 379, and systematic culturing of the explanted lung did not detect M. abscessus. This study describes the course and associated markers of a successful phage treatment of M. abscessus in advanced lung disease.

对患有难治性脓肿分枝杆菌肺部感染和严重囊性纤维化肺部疾病的男性进行静脉注射两种分枝杆菌噬菌体。这些噬菌体经过工程改造，以增强其裂解脓肿分枝杆菌的能力，并被专门选择为对受试者的细菌分离株最有效的噬菌体。在同情使用的情况下，通过分子和代谢测定结合临床评估观察了噬菌体诱导裂解的证据。噬菌体处理前后的脓肿分枝杆菌分离株表现出遗传稳定性，多样性普遍下降，并且对噬菌体或抗生素的耐药性没有增加。针对一种噬菌体的抗噬菌体中和抗体滴度随着时间的推移而增加，但在整个治疗过程中并不妨碍临床改善。受试者在第379天接受肺移植，移植肺的系统培养未检测到脓肿分枝杆菌。这项研究描述了噬菌体成功治疗晚期肺部疾病脓肿分枝杆菌的过程和相关标志物。