Antibacterial activity of high-dose nitric oxide against pulmonary Mycobacterium abscessus disease

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 disease, and examined heterogeneity of response to NO . In the compassionate-use treatment, a 24-year-old CF patient with pulmonary 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. susceptibility tests were performed against patient's isolate and comparison clinical isolates and quantified by Hill's slopes calculated from time-kill curves. 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. susceptibility tests showed a dose-dependent NO effect on susceptibility and significant heterogeneity in response between clinical isolates. The patient's isolate was found to be the least susceptible strain . These results demonstrate heterogeneity in susceptibility to NO and suggest that longer treatment regimens could be required to see the reduction or eradication of more resistant pulmonary strains.