Author/Authors :
Bogdanovski, Kristijan Laboratory of Chronic Airway Infection - Pulmonary Branch - National Heart, Lung, and Blood Institute - National Institutes of Health, Bethesda, MD, USA , Chau, Trisha Laboratory of Chronic Airway Infection - Pulmonary Branch - National Heart, Lung, and Blood Institute - National Institutes of Health, Bethesda, MD, USA , Robinson, Chevalia J. Laboratory of Chronic Airway Infection - Pulmonary Branch - National Heart, Lung, and Blood Institute - National Institutes of Health, Bethesda, MD, USA , MacDonald, Sandra D. Laboratory of Chronic Airway Infection - Pulmonary Branch - National Heart, Lung, and Blood Institute - National Institutes of Health, Bethesda, MD, USA , Peterson, Ann M. Nursing Department - Clinical Center - National Institutes of Health, Bethesda, MD, USA , Mashek, Christine M. Nursing Department - Clinical Center - National Institutes of Health, Bethesda, MD, USA , Wallin, Windy A. Critical Care Therapy Section - Clinical Center - National Institutes of Health, Bethesda, USA , Rimkus, Mark Beyond Air, Garden City, NY, USA , Montgomery, Frederick Beyond Air, Garden City, NY, USA , Silva, Joas Lucas da Laboratory of Chronic Airway Infection - Pulmonary Branch - National Heart, Lung, and Blood Institute - National Institutes of Health, Bethesda, MD, USA , Gupta, Shashank Laboratory of Chronic Airway Infection - Pulmonary Branch - National Heart, Lung, and Blood Institute - National Institutes of Health, Bethesda, MD, USA , Ghaffari, Abdi Beyond Air, Garden City, NY, USA , Zelazny, Adrian M. Department of Laboratory Medicine - Clinical Center - National Institutes of Health, Bethesda, MD, USA , Olivie, Kenneth N. Laboratory of Chronic Airway Infection - Pulmonary Branch - National Heart, Lung, and Blood Institute - National Institutes of Health, Bethesda, MD, USA
Abstract :
Introduction
Mycobacterium abscessus is an emerging pulmonary pathogen with limited treatment options. Nitric oxide (NO) demonstrates antibacterial activity against various bacterial species, including mycobacteria. In this study, we evaluated the effect of adjunctive inhaled NO therapy, using a novel NO generator, in a CF patient with pulmonary M. abscessus disease, and examined heterogeneity of response to NO in vitro.
Methods
In the compassionate-use treatment, a 24-year-old CF patient with pulmonary M. abscessus was treated with two courses of adjunctive intermittent NO, first at 160 p.p.m. for 21 days and subsequently by escalating the dose up to 240 p.p.m. for 8 days. Methemoglobin, pulmonary function, 6 min walk distance (6MWD), qualify of life and sputum microbiology were assessed. In vitro susceptibility tests were performed against patient’s isolate and comparison clinical isolates and quantified by Hill’s slopes calculated from time–kill curves.
Results
M. abscessus lung infection eradication was not achieved, but improvements in selected qualify of life domains, lung function and 6MWD were observed during the study. Inhaled NO was well tolerated at 160 p.p.m. Dosing at 240 p.p.m. was stopped due to adverse symptoms, although methemoglobin levels remained within safety thresholds. In vitro susceptibility tests showed a dose-dependent NO effect on M. abscessus susceptibility and significant heterogeneity in response between M. abscessus clinical isolates. The patient’s isolate was found to be the least susceptible strain in vitro.
Conclusion
These results demonstrate heterogeneity in M. abscessus susceptibility to NO and suggest that longer treatment regimens could be required to see the reduction or eradication of more resistant pulmonary strains.
