Inappropriate antibiotic use for COVID-19 linked to resistance: Study

Taking azithromycin for as little as one day triggers antibiotic resistance in the respiratory tract, according to a first-of-its kind look by scientists at UC San Francisco of the changes that occur in the microbiome of hospitalized patients who were treated for COVID-19.

Azithromycin is one of the most widely used antibiotics in the world, and it is essential for treating certain classes of bacterial infections that cause strep throat, pneumonia, and sexually transmitted diseases. But it does not work against viruses.

Early in the pandemic, azithromycin was widely used after small studies suggested it might have therapeutic benefit. Randomized clinical trials later showed it did not work, but the drug continued to be prescribed to patients with respiratory illnesses.

“We’ve known for years that antibiotics don’t treat viral infections, but these results were striking,” said Chaz Langelier, MD, PhD. “That we could see resistance genes turning on in the respiratory tract within a day tells us the consequences of unnecessary antibiotic use aren’t theoretical or long-term. They’re immediate, measurable, and biologically real.”

The results, published March 16 in Nature Microbiology, are from a multi-center genomic study that was funded in part by the National Institute of Allergy and Infectious Diseases (NIAID).

Researchers followed 1,164 COVID-19 patients who had been hospitalized at more than 20 U.S. hospitals between May of 2020 and March of 2021, before COVID vaccines were widely available.

They compared the patients who were given azithromycin to those who received no antibiotics, as well as to patients who were given other antibiotics.

Azithromycin changed the mix of microbes in the upper airway. Some normally harmless bacteria decreased, while potentially harmful bacteria became more common. These changes persisted for more than a week.

Next, the researchers will look at whether other widely used antibiotics, such as amoxicillin and ceftriaxone, have similar effects in hospitalized patients. 

Reference:

Glascock, A., Maguire, C., Phan, H.V. et al. Empiric azithromycin alters the upper respiratory microbiome and resistome without anti-inflammatory benefit in COVID-19. Nat Microbiol (2026). https://doi.org/10.1038/s41564-026-02285-8