Daijiworld Media Network - Boston
Boston, Feb 11: Drug-resistant pneumonia continues to pose a serious challenge in intensive care units, where treatment options are limited, particularly against bacteria such as Pseudomonas aeruginosa, which causes nearly one in five hospital-acquired pneumonias and is often resistant to multiple drugs.
Researchers at Massachusetts General Hospital, Boston, affiliated with Harvard Medical School, have reported that a gas already used in neonatal care may help tackle such infections. In a study published in Science Translational Medicine, the team found that high doses of inhaled nitric oxide significantly reduced drug-resistant Pseudomonas infections in a large-animal ICU model.
The human body naturally produces nitric oxide, and doctors routinely use it at low doses of 20–80 parts per million (ppm) to widen blood vessels in the lungs of patients with acute respiratory failure. However, the research team explored much higher concentrations for their antimicrobial potential.
Lorenzo Berra, associate professor of anaesthesia at Harvard Medical School and a senior author of the study, said earlier research guided the approach. “At the low doses commonly used in clinical practice, nitric oxide mainly acts as a selective pulmonary vasodilator,” he said, adding that a 2021 mouse study provided the rationale for testing 300 ppm as a threshold for antimicrobial activity.
To simulate real ICU conditions, researchers studied 16 ventilated pigs with pneumonia caused by multidrug-resistant P. aeruginosa. The animals received intensive care for three days after bacteria were introduced directly into their lungs. Half were given repeated short bursts of inhaled nitric oxide at 300 ppm, while the others received standard supportive care without antibiotics.
The team monitored oxygen levels, lung stiffness, blood pressure and infection markers throughout the study. The findings showed that treated animals had 99 per cent lower bacterial counts in their lungs, along with improved oxygenation and lung function. Researchers suggested that nitric oxide may restore chemical signalling in infected lungs, improving oxygen transfer and reducing the need for blood pressure-supporting drugs.
While the results are promising, experts have urged caution. Paul H Edelstein, professor of pathology and laboratory medicine at the University of Pennsylvania, noted that although the animals initially improved, their lung function later deteriorated. He said this could be due to toxic effects of nitric oxide, including elevated methemoglobin levels or direct lung injury.
He also questioned the durability of the antimicrobial effect, noting that even a small number of remaining bacteria could rapidly multiply once treatment stops. However, the study found that treated animals had significantly lower levels of immune chemicals that cause lung swelling and fluid buildup, an effect that persisted during the critical early days of severe pneumonia.
To assess safety, the researchers conducted a small phase 1 trial involving 10 healthy volunteers who inhaled nitric oxide at 300 ppm for 30 minutes, three times a day for five days. Methemoglobin levels rose briefly but remained well below safety limits, and no serious adverse effects were reported. The team also administered the treatment to two critically ill ICU patients to test feasibility, demonstrating that it could be delivered without immediate serious complications.
Prof Berra said further clinical trials are essential to determine whether the treatment improves patient outcomes, stressing that high-dose nitric oxide would complement, not replace, standard ICU care. He also pointed to practical challenges, noting that most hospitals are not equipped to deliver nitric oxide at such high concentrations and would require specialised equipment and trained staff.
Despite the hurdles, researchers believe the study marks an important step toward exploring alternative strategies against drug-resistant infections. However, experts caution that more evidence is needed before the approach can be widely adopted in clinical practice.