Abstract Introduction In people with cystic fibrosis (pwCF) with advanced lung disease complicated by Mycobacterium abscessus, treatment options are limited and duration of therapy is not evidenced-based. Chest CT and molecular biomarkers play an important role in monitoring all aspects of care, including diagnosis of disease, and treatment response. In this case-study, two engineered mycobacteriophages were administered intravenously, alongside CFTR modulator therapy, and antibiotics, to a single CF patient with treatment-refractory M. abscessus pulmonary infection and severe lung disease1. Successful control of the infection allowed for bilateral lung transplant, and no evidence of persistent infection post-transplant. Here we build on these results by evaluating how quantitative CT metrics (bronchial dimensions, mucus plug counts, consolidation), could contribute to monitor the response to phage therapy and to assess the efficacy and safety. Methods After 1582 days of positive cultures for M. abscessus and multidrug antibiotic treatments patient was treated with phage therapy. Chest CT scans were obtained at regular intervals between baseline and day 81 post-phage therapy to monitor structural lung changes. In this interval the patient was also started on CFTR modulator therapy. The patient eventually underwent lung transplantation on day 379 after which regular CTs were continued. CT images were analyzed using LungQ (Thirona, Nijmegen), an AI-driven software to quantify bronchi-arterial (BA) dimensions, mucus plug (MP) counts and volume, and high attenuation volume expressed as % lung volume (HAV%). Key LungQ-BA metrics for this study are the ratio between the bronchial wall area and outer area (Bwa/Boa) and MP counts. Results M. abscessus cultures became negative on day 116 post-phage therapy and remained negative also after transplantation1. From baseline to transplantation, Bwa/Boa reduced from 0.48 to 0.44, MP counts from 296 to 41 and HAV% from 8% to 0%. After lung transplantation CT showed progressive structural changes which fitted the diagnosis of rejection. In this period Bwa/Boa increased from 0.25 to 0.43, and HAV% from 0% to 34%, while MP remained absent. Conclusion CT-metrics allowed close monitoring of relevant structural changes to assess the effectiveness and safety of phage therapy for the treatment-refractory M. abscessus pre- and post-lung transplantation in a CF patient with severe lung disease. 1. Host and pathogen response to bacteriophage engineered against Mycobacterium abscessus lung infection. Nick, Jerry A. et al. Cell, Volume 185, Issue 11, 1860 - 1874.e12 This abstract is funded by: NJH
Tiddens et al. (Fri,) studied this question.