Inhaled nitric oxide treats multidrug-resistant Pseudomonas pneumonia

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From the editor's summary and abstract:

"Editor’s summary

The global crisis of antimicrobial resistance urgently requires new therapeutic approaches.

Inhaled high-dose nitric oxide (NO) has potential antimicrobial activity against bacteria, viruses, and fungi.

In this study, Yu et al. first developed a swine model of Pseudomonas aeruginosa pneumonia and demonstrated that inhalation of 300 ppm of NO effectively reduced bacterial burden and improved lung function. The authors then showed that this inhaled high-dose NO was safe both in healthy individuals and in two patients in the intensive care unit with P. aeruginosa pneumonia. There were no adverse outcomes during 6 years of follow-up in another group of patients who received high-dose NO. ...

Abstract

Antibiotic resistance in respiratory infections is an escalating global concern that requires innovative antimicrobial approaches.

Pseudomonas aeruginosa is a common multidrug-resistant pathogen and a major cause of hospital-acquired pneumonia. Accumulating evidence suggests that, at high doses, inhaled nitric oxide (iNO) acts as a potent antimicrobial agent. This study evaluated the efficacy and safety of iNO at 300 parts per million (iNO300) as a treatment for P. aeruginosa infection.

In vitro, P. aeruginosa exhibited a dose-dependent reduction when exposed to an NO donor. In a mechanically ventilated swine model of P. aeruginosa pneumonia, intermittent iNO300 therapy resulted in a two-log reduction in bacterial burden, improved oxygenation and lung compliance, and reduced histopathological lung injury.

A phase 1 clinical trial in 10 healthy individuals confirmed the safety of intermittent iNO300 therapy with no adverse events.

In two critically ill patients with multidrug-resistant bacteria, who were in the intensive care unit, iNO300 was well tolerated, demonstrating clinical feasibility. Long-term follow-up of patients exposed to high-dose iNO for more than 6 years revealed no adverse outcomes.

Our findings establish iNO300 as a promising antimicrobial agent against P. aeruginosa pneumonia, warranting further clinical evaluation."

Inhaled nitric oxide at 300 ppm treats multidrug-resistant Pseudomonas pneumonia in swine and is safe in humans | Science Translational Medicine