High-Dose Inhaled Nitric Oxide Emerges as Promising Antimicrobial Therapy

Excessive antibiotic use has accelerated the emergence of bacterial resistance to standard therapies, fueling a global health crisis projected to cause more than 10 million deaths annually by 2050. Among the most concerning pathogens, multidrug-resistant Pseudomonas aeruginosa accounts for approximately 20% of hospital-acquired pneumonia cases and is associated with severe disease and increased mortality. To address this challenge, investigators now report that high-dose inhaled nitric oxide demonstrates antimicrobial activity in preclinical models and was safe and feasible in early human exposure studies.

A research team at Mass General Brigham (Boston, MA, USA) investigated whether brief exposures to high concentrations of inhaled nitric oxide (iNO), a therapeutic gas with established use in critical care, could exert direct antipseudomonal effects while remaining tolerable for patients. n vitro experiments first showed dose-dependent killing of Pseudomonas aeruginosa using nitric oxide–releasing compounds. The team then tested the approach in a pig model of experimental pneumonia, where treatment with high-dose iNO at 300 parts per million significantly reduced bacterial burden compared with untreated controls and was associated with improved oxygenation and other indicators of lung infection.

Feasibility and safety were then assessed in humans through repeated exposure to high-dose inhaled nitric oxide. The investigators evaluated 10 healthy volunteers and two critically ill patients with multidrug-resistant bacterial infections, finding that treatment was well tolerated with no serious safety concerns. A retrospective analysis of patients who received high-dose inhaled nitric oxide in clinical settings, primarily during the COVID-19 pandemic, further supported its safety profile. The findings were published in Science Translational Medicine.

“These results suggest a promising strategy that could complement existing treatments. However, rigorous clinical trials are essential before this approach can be considered for routine clinical use,” said senior author Lorenzo Berra, MD, Mass General Brigham Department of Anesthesia, Critical Care and Pain Medicine: 

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