Case Study: Host and Pathogen Response to Bacteriophage Engineered Against Mycobacterium abscessus Lung Infection

Two engineered mycobacteriophages were administered intravenously with antibiotics to a male with treatment-refractory Mycobacterium abscessus pulmonary infection and severe cystic fibrosis lung disease. Evidence of phage-induced lysis was observed using molecular and metabolic assays within days of phage treatment initiation, followed by computerized tomography assessed improvement by day 81, and conversion of airway cultures to predominately negative by day 118. Pan-genome analysis of 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. 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 successful phage treatment of M. abscessus in advanced lung disease.