Drug-resistant pneumonia remains a serious complication in intensive care units, where treatment options are limited. Pseudomonas aeruginosa in particular causes about one in five hospital pneumonias and often resists multiple drugs.
A research team at the Massachusetts General Hospital, Boston, affiliated with Harvard Medical School, has reported that a gas already used in neonatal care may have a role in addressing such infections. In a study published in Science Translational Medicine, researchers found that a high dose of inhaled nitric oxide reduced drug-resistant Pseudomonas in a large-animal ICU model.
Antimicrobial agent
The human body naturally produces nitric oxide; doctors also use it at low doses, typically 20-80 ppm, to widen blood vessels in the lungs of patients with acute respiratory failure.
Lorenzo Berra, associate professor of anaesthesia at Harvard Medical School and a senior author of the study, said the decision to test much higher concentrations was guided by earlier findings.
“At the low doses commonly used in clinical practice, nitric oxide mainly acts as a selective pulmonary vasodilator,” he said. In 2021, a mouse study by his colleagues “provided the biological rationale for selecting 300 ppm as the threshold likely required for antimicrobial activity.”
To test the approach in a setting mirroring a human ICU, the researchers studied 16 ventilated pigs with pneumonia caused by multidrug-resistant P. aeruginosa. They introduced the bacteria directly into the lungs and afforded the animals intensive care for three days.
One half received short, repeated bursts of inhaled nitric oxide at 300 ppm and the other half received standard supportive care alone, sans antibiotics. The team continuously tracked oxygen levels, lung stiffness, blood pressure, and infection markers, and compared how the two groups changed over time.
The study found that treated animals had 99% lower lung bacterial counts along with better oxygenation and lung function. The authors suggested the gas may help restore chemical signalling in the lung disrupted by severe infection, allowing it to transfer oxygen more efficiently and reducing the need for drugs to maintain blood pressure.
Prof. Berra said the findings suggest the approach could be relevant to critically ill patients, though further testing is required.
Promise and limits
Paul H. Edelstein, professor of pathology and laboratory medicine at University of Pennsylvania, supported the possibility of this treatment but said the results should be interpreted cautiously.
“The animals initially improved, but later their lungs grew stiffer and less able to oxygenate the blood while they were still on the gas,” he said, adding that the harm could have resulted from the toxic effects of nitric oxide, either through elevated methemoglobin, which blocks oxygen delivery, or through direct lung injury.
He also questioned the durability of the antimicrobial effects. “While 99% sounds high, leaving even 1% means millions of organisms remain, making a rapid rebound likely once treatment stops.”
Although some bacteria remained, the treated animals had far lower levels of the immune chemicals that cause the lungs to swell and fill with fluid, a chain reaction that cuts off oxygen. This effect persisted over the first two days, when severe pneumonia typically worsens and begins to damage other organs.
To assess whether the doses could be delivered safely, the researchers conducted a small phase 1 study in 10 healthy human volunteers. Participants inhaled nitric oxide at 300 ppm for 30 minutes, thrice a day for five days. Methemoglobin levels rose briefly, peaking at 4.5%, well below the 10% safety threshold. The team reported no serious adverse effects.
The group also delivered the high-dose gas to two critically ill ICU patients to test feasibility. The study didn’t report whether the patients improved; instead, it showed that the treatment could be administered without immediate serious complications.
“Proving that this treatment improves patient outcomes requires a dedicated clinical efficacy trial,” Prof. Berra said. He emphasised that the gas would be used alongside standard ICU care, not as a replacement.
Even if future trials confirm clinical benefits, practical barriers remain. Most hospitals are not equipped to deliver nitric oxide at high concentrations and the process requires specialised machinery and trained staff.
“The biggest obstacle would be technical, operational, and monitoring, not biological,” he said. Standard systems are capped at 80 ppm and higher doses require continuous monitoring to prevent nitrogen dioxide formation and methemoglobin accumulation, which the researchers kept below safety limits in the study.
For Prof. Edelstein, the work represents an important starting point, but “until researchers can show the gas works at non-toxic exposures and delivers lasting benefit, the excitement is premature.”
Anirban Mukhopadhyay is a geneticist by training and science communicator from New Delhi.
Published – February 11, 2026 07:00 am IST
