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Empiric azithromycin alters the upper respiratory microbiome and resistome without anti-inflammatory benefit in COVID-19
Journal article   Open access   Peer reviewed

Empiric azithromycin alters the upper respiratory microbiome and resistome without anti-inflammatory benefit in COVID-19

Abigail Glascock, Cole Maguire, Hoang Van Phan, Emily C. Lydon, Joanna Schaenman, Carolyn S. Calfee, Esther Melamed, John Greenland, David B. Corry, Farrah Kheradmand, …
Nature microbiology
16 Mar 2026
PMID: 41840216
Featured in Collection :   Drexel's Newest Publications
url
https://doi.org/10.1038/s41564-026-02285-8View
Published, Version of Record (VoR)CC BY V4.0 Open

Abstract

Life Sciences & Biomedicine Science & Technology Microbiology
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.

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