Host and pathogen response to bacteriophage engineered against Mycobacterium abscessus lung infection

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.

Automated summary

This study describes a successful phage treatment of treatment-refractory Mycobacterium abscessus pulmonary infection in a patient with severe lung disease. The phages used in the treatment were engineered to enhance their ability to lyse M. abscessus and were specifically selected based on their effectiveness against the patient's bacterial isolate. The treatment resulted in genetic stability of the bacterial isolate and improved clinical symptoms in the patient.