Preprint
Empiric Azithromycin in COVID-19 Impacts the Respiratory Microbiome and Antimicrobial Resistome without Anti-inflammatory Benefit
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20 Jun 2025
PMID: 40585204
Abstract
Azithromycin is often prescribed unnecessarily for respiratory infections, many of which are viral. During the COVID-19 pandemic, its use was widespread, in part due to alleged therapeutic benefits, which have since been disproven. Here, we sought to understand the impact of azithromycin exposure on the respiratory microbiome, antimicrobial resistome, and host immune response in a prospective multicenter cohort of 1164 patients hospitalized for SARS-CoV-2 infection. Using longitudinal nasal metatranscriptomics, we compared patients treated with azithromycin (n=366, 31.4%) to those who received no antibiotics (n=474, 40.7%) or antibiotics other than azithromycin (n=324, 27.8%). We found that azithromycin treatment altered the community composition of the nasal microbiome, reducing bacterial relative abundance, increasing fungal relative abundance, and increasing potentially pathogenic taxa such as
and
Azithromycin treatment was most notably associated with increases in the number of detectably expressed macrolide/lincosamide/streptogramin (MLS) antimicrobial resistance genes, as well as their relative proportion in the resistome, with changes observable after one day of exposure. Of the MLS resistance genes, the expression of
,
and
increased the most in patients receiving azithromycin. Correlation analyses demonstrated that MLS resistance gene expression was significantly associated with the abundance of several taxa, including both commensal (e.g.,
) and potentially pathogenic genera (e.g.,
Assessment of the peripheral blood and upper airway host transcriptome demonstrated no differences in the expression of inflammatory genes. Taken together, our findings demonstrate that azithromycin treatment in COVID-19 leads to dysbiosis of the upper respiratory microbiome and changes in the expression of MLS resistance genes, without apparent anti-inflammatory benefit.
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Details
- Title
- Empiric Azithromycin in COVID-19 Impacts the Respiratory Microbiome and Antimicrobial Resistome without Anti-inflammatory Benefit
- Creators
- Charles Langelier - University of California, San FranciscoAbigail Glascock - Chan Zuckerberg Initiative (United States)Cole Maguire - The University of Texas at AustinHoang Van PhanEmily Lydon - University of California, San FranciscoCarolyn Calfee - University of California, San FranciscoImpacc NetworkDavid Corry - Baylor College of MedicineFarrah Kheradmand - Baylor College of MedicineLindsey Baden - Brigham and Women's HospitalRafick-Pierre SekalyGrace McComsey - Case Western Reserve UniversityElias Haddad - Drexel UniversityCharles Cairns - Drexel UniversityBali Pulendran - Stanford UniversityAna Fernandez-Sesma - Icahn School of Medicine at Mount SinaiViviana Simon - Icahn School of Medicine at Mount SinaiJordan Metcalf - University of Oklahoma Health Sciences CenterNelson HiguitaWilliam MesserMark Davis - Stanford UniversityKari C Nadeau - Stanford UniversityMonica Kraft - University of ArizonaChris Bime - University of ArizonaJoanna SchaenmanDavid ErleMark Atkinson - University of FloridaLauren I R Ehrlich - The University of Texas at AustinEsther Melamed - The University of Texas at AustinRuth Montgomery - Yale UniversityAlbert Shaw - Yale UniversityCatherine Hough - Oregon Health & Science UniversityLinda Geng - Stanford UniversityAnnmarie HochDavid Hafler - Yale UniversityAlison Augustine - National Institute of Allergy and Infectious DiseasesPatrice Becker - National Institutes of HealthBjoern Peters - La Jolla Institute for ImmunologyAl Ozonoff - Boston Children's HospitalSeunghee Kim-Schulze - Icahn School of Medicine at Mount SinaiFlorian Krammer - Icahn School of Medicine at Mount SinaiSteven Bosinger - Emory UniversityWalter Eckalbar - University of California, San FranciscoMatthew Altman - Benaroya Research InstituteMichael Wilson - University of California, San FranciscoLeying Guan - Yale UniversityHolden Maecker - Stanford UniversityHanno Steen - Boston Children's MuseumJoann Diray-ArceNadine Rouphael - Emory UniversitySteven Kleinstein - Yale UniversityElaine Reed - University of California, Los AngelesOfer Levy - Boston Children's HospitalVictoria Chu
- Publication Details
- Research square
- Resource Type
- Preprint
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine); Emergency Medicine
- Other Identifier
- 991022061053904721