Language

English

Publication Date

4-1-2026

Journal

Nature Microbiology

DOI

10.1038/s41564-026-02285-8

PMID

41840216

PMCID

PMC13056551

PubMedCentral® Posted Date

3-16-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Azithromycin is a widely used antibiotic and was frequently used to treat hospitalized patients during the COVID-19 pandemic. The impact of empiric azithromycin use on the respiratory microbiome in patients with viral respiratory infections is unclear. Here we used longitudinal metatranscriptomics on nasal swabs from a prospective multicentre cohort of 1,164 patients hospitalized for COVID-19. We compared the upper respiratory microbiome, resistome and systemic immune response in patients treated with azithromycin (n = 366) with those who received no antibiotics (n = 474) or other antibiotics (n = 324). We found that azithromycin altered microbiome composition and increased the expression and relative proportion of macrolide/lincosamide/streptogramin (MLS) resistance genes. These changes occurred after 1 day of exposure and persisted for over a week. MLS resistance gene expression was associated with commensals and potential pathogens, while there were no differences in host inflammatory gene expression in blood and airways. This demonstrates that empiric azithromycin treatment impacts the upper respiratory microbiome and resistome without apparent anti-inflammatory benefit.

Keywords

Humans, Azithromycin, Anti-Bacterial Agents, Microbiota, Female, Male, SARS-CoV-2, Prospective Studies, COVID-19, Middle Aged, Respiratory System, COVID-19 Drug Treatment, Anti-Inflammatory Agents, Aged, Pandemics, Bacteria, Metagenomics, Clinical microbiology, Viral infection, Microbiome

Published Open-Access

yes

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