Inhaled Nitric Oxide Shows Promise Against Drug-Resistant Pneumonia, Early Trials Suggest
A novel approach to combating antibiotic-resistant bacteria is showing early promise. Researchers have found that high-dose inhaled nitric oxide (iNO) demonstrates antimicrobial activity against Pseudomonas aeruginosa, a dangerous pathogen responsible for a significant portion of hospital-acquired pneumonia, and appears safe for human use.
The looming threat of antibiotic resistance is one of the most pressing global health challenges. The World Health Organization projects that antimicrobial resistance could lead to more than 10 million deaths annually by 2050. Pseudomonas aeruginosa, a particularly resilient bacterium, accounts for roughly one-fifth of pneumonia cases contracted in hospitals and is linked to severe illness and increased mortality rates.
For decades, nitric oxide has been a life-saving therapy for newborns with congenital heart disease. Now, nearly 30 years after its initial success in this context, a team at Massachusetts General Hospital, part of the Mass General Brigham healthcare system, is exploring its potential as an antibacterial agent. Their findings, published in Science Translational Medicine, suggest iNO could offer a new weapon in the fight against drug-resistant infections.
“This study provides a translational foundation rather than a definitive clinical solution,” explained a lead researcher. “Our findings demonstrate strong preclinical antipseudomonal effects together with reassuring human safety data.”
The research involved a multi-stage approach. Initially, scientists demonstrated that nitric oxide-releasing compounds effectively killed Pseudomonas aeruginosa in laboratory settings. Subsequent experiments with pigs infected with P. aeruginosa pneumonia revealed that treatment with high-dose iNO (300 parts per million) reduced bacterial load and improved lung function compared to untreated animals.
To evaluate safety and feasibility in humans, the team administered repeated high-dose iNO to 10 healthy volunteers and two critically ill patients already battling multidrug-resistant bacterial infections. The treatment was well-tolerated, with no serious adverse effects reported. A retrospective review of patients who received high-dose iNO during clinical care, particularly during the COVID-19 pandemic, further reinforced the safety profile of this approach.
“These results justify the careful design of phase 2 and phase 3 clinical trials to formally assess clinical efficacy,” stated a co-lead investigator.
A senior author emphasized the potential of this strategy, noting, “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.”
The research team acknowledges that further investigation is crucial. While the initial findings are encouraging, large-scale clinical trials are necessary to confirm the efficacy of iNO as a treatment for multidrug-resistant Pseudomonas aeruginosa pneumonia and to determine optimal dosage and treatment protocols.
Reference: Yu B, Safaee Fakhr B, Bry L, et al. Inhaled nitric oxide at 300 ppm treats multidrug-resistant Pseudomonas pneumonia in swine and is safe in humans. Sci Transl Med. 2026;18(833):eady2646. doi: 10.1126/scitranslmed.ady2646.
