Nat Microbiol

Azithromycin reshapes respiratory microbiome in COVID-19 without clinical benefit, study finds

March 18, 2026

A multi‑center genomic study found that empiric azithromycin significantly altered the upper respiratory microbiome and resistome in hospitalized COVID‑19 patients, with no anti‑inflammatory benefit. Researchers followed 1,164 patients hospitalized across more than 20 U.S. medical centers between May 2020 and March 2021. Those who received azithromycin showed rapid shifts in the upper‑airway microbial community: normally harmless bacteria decreased, potentially pathogenic bacteria became more common, and macrolide‑class resistance gene expression increased after just one day of exposure. These changes persisted for over a week. Patients receiving no antibiotics or other antibiotics didn’t show these same patterns.

Clinical takeaway: Avoid empiric azithromycin in COVID-19 patients unless there's clear evidence of bacterial infection, as it offers no anti-inflammatory benefit and may promote antimicrobial resistance.

Source:

Glascock A, et al; IMPACC Network. (2026, March 16). Nat Microbiol. Empiric azithromycin alters the upper respiratory microbiome and resistome without anti-inflammatory benefit in COVID-19. https://pubmed.ncbi.nlm.nih.gov/41840216/