There is an increasing prevalence of nontuberculous mycobacteria pulmonary disease (NTM-PD) in the US. Treatment of NTM-PD typically requires multiple medications, which can be associated with unpleasant morbidity and eradication of infection is difficult. Therefore, there is a critical need for novel effective and well-tolerated therapies. Recent in vitro data and case reports have suggested that nitric oxide, inhaled as a gas (gNO), has antimicrobial activity against NTM. We sought to investigate the effect of gNO in patients with NTM-PD in an open-label proof of concept trial.
Eligible participants had NTM-PD with persistently positive respiratory cultures for NTM even if on antibiotic treatment. Participants were treated with gNO for 50 min three times daily, five days per week, for three weeks (total of 15 treatment days).
Ten participants, of whom nine were on long-term NTM antibiotic therapy, were enrolled. All participants completed the regimen without interruption or discontinuation. Small increases in methemoglobin were noted during treatment, and all resolved to baseline within 2 h. Four participants (40%) met the primary outcome measure of negative sputum cultures after three weeks of therapy. Following treatment discontinuation, three of these participants were again culture positive during the 3-month post-treatment monitoring period, although with measures suggesting low bacterial burden.
Patients tolerated a 3-week regimen of gNO without safety concerns, and despite highly refractory disease four individuals completed the study with negative cultures, although three were again positive in subsequent months. These data support further investigation of gNO as a potential therapy for NTM-PD.
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- Pathogenic nontuberculous mycobacteria resist and inactivate cathelicidin: implication of a novel role for polar mycobacterial lipids.PLoS One. 2015; 10e0126994
- US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis: executive summary.Thorax. 2016; 71: 88-90
- Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline.Clinic. Infect. Dis. Offc. Pub. Infect. Dis. Soc. Am. 2020; 71: 905-913
- Clinical and microbiologic outcomes in patients receiving treatment for Mycobacterium abscessus pulmonary disease.Clinic. Infect. Dis. Offc. Pub. Infect. Dis. Soc. Am. 2011; 52: 565-571
- Microbiologic outcome of interventions against Mycobacterium avium complex pulmonary disease: a systematic review.Chest. 2018; 153: 888-921
- Infrared detection and nitric oxide treatment of bovine respiratory disease.Online J. Vet. Res. 2006; 10: 7-16
- Gaseous nitric oxide to treat antibiotic resistant bacterial and fungal lung infections in patients with cystic fibrosis: a phase I clinical study.Infection. 2016; 44: 513-520
- Compassionate nitric oxide adjuvant treatment of persistent Mycobacterium infection in cystic fibrosis patients.Pediatr. Infect. Dis. J. 2018; 37: 336-338
- Validation of the Leicester Cough Questionnaire in Non-cystic Fibrosis Bronchiectasis.2009: 125-131
- The st george's respiratory questionnaire.Respir. Med. 1991; 85 (; discussion 3-7): 25-31
- Treatment of infections caused by rapidly growing mycobacteria in the era of the newer macrolides.Res. Microbiol. 1996; 147: 30-35
- Time to positivity in liquid culture predicts colony forming unit counts of Mycobacterium tuberculosis in sputum specimens.Tuberculosis. 2014; 94: 148-151
Published online: December 01, 2022
Accepted: November 30, 2022
Received: July 14, 2022
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