Non-tuberculous mycobacteria infection treated with intermittently inhaled high-dose nitric oxide

Goldbart, Aviv; Gatt, Dvir; Golan‐Tripto, Inbal

doi:10.1136/bcr-2021-243979

Cited by 11 publications

(7 citation statements)

References 12 publications

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“…The use of inhaled NO by Yaacoby-Bianu et al in 2018 in two cystic fibrosis patients with pulmonary MAB resulted in a reduction in bacterial load as measured by quantitative polymerase chain [ 78 ]. The use of inhaled NO by Goldbart et al in a CF patient with pulmonary MAB showed bacterial growth inhibition as well as improvement of lung pathology on CT [ 79 ]. The observations from these case reports show that NO is safe and well tolerated and could play a crucial role in the treatment of NTM pulmonary disease [ 71 , 78 , 79 ].…”

Section: Methodsmentioning

confidence: 99%

Diagnosis and Management of Pulmonary NTM with a Focus on Mycobacterium avium Complex and Mycobacterium abscessus: Challenges and Prospects

et al. 2022

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Background: Nontuberculous mycobacteria (NTM) are ubiquitous. NTM can affect different organs and may cause disseminated diseases, but the pulmonary form is the most common form. Pulmonary NTM is commonly seen in patients with underlying diseases. Pulmonary Mycobacterium avium complex (MAC) is the most common NTM disease and M. abscessus (MAB) is the most challenging to treat. This review is prepared with the following objectives: (a) to evaluate new methods available for the diagnosis of pulmonary MAC or MAB, (b) to assess advances in developing new therapeutics and their impact on treatment of pulmonary MAC or MAB, and (c) to evaluate the prospects of preventive strategies including vaccines against pulmonary MAC or MAB. Methods: A literature search was conducted using PubMed/MEDLINE and multiple search terms. The search was restricted to the English language and human studies. The database query resulted in a total of 197 publications. After the title and abstract review, 64 articles were included in this analysis. Results: The guidelines by the American Thoracic Society (ATS), European Respiratory Society (ERS), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), and Infectious Diseases Society of America (IDSA) are widely applicable. The guidelines are based on expert opinion and there may be a need to broaden criteria to include those with underlying lung diseases who may not fulfill some of the criteria as ‘probable cases’ for better follow up and management. Some cases with only one culture-positive sputum sample or suggestive histology without a positive culture may benefit from new methods of confirming NTM infection. Amikacin liposomal inhalation suspension (ALIS), gallium containing compounds and immunotherapies will have potential in the management of pulmonary MAC and MAB. Conclusions: the prevalence of pulmonary NTM is increasing. The efforts to optimize diagnosis and treatment of pulmonary NTM are encouraging. There is still a need to develop new diagnostics and therapeutics.

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Section: Methodsmentioning

confidence: 99%

Diagnosis and Management of Pulmonary NTM with a Focus on Mycobacterium avium Complex and Mycobacterium abscessus: Challenges and Prospects

et al. 2022

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“…The authors also hypothesized that prolonged intermittent iNO treatment beyond 3 weeks could increase the susceptibility of NTM biofilm to antibiotics and achieve improved bactericidal activity in CF airways [ 71 ]. However, more recent case reports showed that even longer durations (up to 29 days) and higher doses of iNO (up to 250 ppm) failed to induce the eradication of infective microorganisms [ 72 , 73 ].…”

Section: High-dose Exogenous No As An Antimicrobial Treatmentmentioning

confidence: 99%

High Doses of Inhaled Nitric Oxide as an Innovative Antimicrobial Strategy for Lung Infections

et al. 2022

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Since the designation of nitric oxide as “Molecule of the Year” in 1992, the scientific and clinical discoveries concerning this biomolecule have been greatly expanding. Currently, therapies enhancing the release of endogenous nitric oxide or the direct delivery of the exogenous compound are recognized as valuable pharmacological treatments in several disorders. In particular, the administration of inhaled nitric oxide is routinely used to treat patients with pulmonary hypertension or refractory hypoxemia. More recently, inhaled nitric oxide has been studied as a promising antimicrobial treatment strategy against a range of pathogens, including resistant bacterial and fungal infections of the respiratory system. Pre-clinical and clinical findings have demonstrated that, at doses greater than 160 ppm, nitric oxide has antimicrobial properties and can be used to kill a broad range of infectious microorganisms. This review focused on the mechanism of action and current evidence from in vitro studies, animal models and human clinical trials of inhaled high-dose nitric oxide as an innovative antimicrobial therapy for lung infections.

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“…With several clinical trials under way (NCT02498535; refs. [ 119 , 120 ]), success in the application of NO as an antibiofilm agent might be based on a combination of antimicrobial, antibiofilm, and host physiological effects [ 121 ]. The antimicrobial peptide LL-37 has been shown to possess a potent antibiofilm, rather than antimicrobial activity against various pathogens, such as P. aeruginosa and Escherichia coli ( Table 2 ; refs.…”

Section: Innovative Strategies To Overcome Antimicrobial Tolerance In...mentioning

confidence: 99%

Innovative Strategies to Overcome Antimicrobial Resistance and Tolerance

et al. 2022

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Antimicrobial resistance and tolerance are natural phenomena that arose due to evolutionary adaptation of microorganisms against various xenobiotic agents. These adaptation mechanisms make the current treatment options challenging as it is increasingly difficult to treat a broad range of infections, associated biofilm formation, intracellular and host adapted microbes, as well as persister cells and microbes in protected niches. Therefore, novel strategies are needed to identify the most promising drug targets to overcome the existing hurdles in the treatment of infectious diseases. Furthermore, discovery of novel drug candidates is also much needed, as few novel antimicrobial drugs have been introduced in the last two decades. In this review, we focus on the strategies that may help in the development of innovative small molecules which can interfere with microbial resistance mechanisms. We also highlight the recent advances in optimization of growth media which mimic host conditions and genome scale molecular analyses of microbial response against antimicrobial agents. Furthermore, we discuss the identification of antibiofilm molecules and their mechanisms of action in the light of the distinct physiology and metabolism of biofilm cells. This review thus provides the most recent advances in host mimicking growth media for effective drug discovery and development of antimicrobial and antibiofilm agents.

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Non-tuberculous mycobacteria infection treated with intermittently inhaled high-dose nitric oxide

Cited by 11 publications

References 12 publications

Diagnosis and Management of Pulmonary NTM with a Focus on Mycobacterium avium Complex and Mycobacterium abscessus: Challenges and Prospects

Diagnosis and Management of Pulmonary NTM with a Focus on Mycobacterium avium Complex and Mycobacterium abscessus: Challenges and Prospects

High Doses of Inhaled Nitric Oxide as an Innovative Antimicrobial Strategy for Lung Infections

Innovative Strategies to Overcome Antimicrobial Resistance and Tolerance

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