| Literature DB >> 35568033 |
Jerry A Nick1, Rebekah M Dedrick2, Alice L Gray3, Eszter K Vladar3, Bailey E Smith2, Krista G Freeman2, Kenneth C Malcolm4, L Elaine Epperson5, Nabeeh A Hasan5, Jo Hendrix6, Kimberly Callahan5, Kendra Walton5, Brian Vestal5, Emily Wheeler4, Noel M Rysavy4, Katie Poch4, Silvia Caceres4, Valerie K Lovell4, Katherine B Hisert7, Vinicius Calado de Moura4, Delphi Chatterjee8, Prithwiraj De8, Natalia Weakly5, Stacey L Martiniano9, David A Lynch10, Charles L Daley7, Michael Strong5, Fan Jia5, Graham F Hatfull11, Rebecca M Davidson5.
Abstract
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.Entities:
Keywords: CFTR modulator therapy; Mycobacterium abscessus; Mycobacterium avium; NTM; bacteriophages; cystic fibrosis; immunoglobulin; lipoarabinomannan; lung transplant; nontuberculous mycobacterial lung disease
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Year: 2022 PMID： 35568033 DOI： 10.1016/j.cell.2022.04.024
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 66.850