Journal Article Ahead of print
PubMed: 41840216 DOI: 10.1038/s41564-026-02285-8
Empiric azithromycin alters the upper respiratory microbiome and resistome without anti-inflammatory benefit in COVID-19.
Nat Microbiol
Authors: Abigail Glascock, Cole Maguire, Hoang Van Phan, Emily C Lydon, Joanna Schaenman, Carolyn S Calfee, Esther Melamed, John Greenland, David B Corry, Farrah Kheradmand, Lindsey R Baden, Rafick Sekaly, Grace A McComsey, Elias K Haddad, Charles B Cairns, Linda N Geng, Bali Pulendran, Ana Fernandez-Sesma, Viviana Simon, Jordan P Metcalf, Nelson I Agudelo Higuita, William B Messer, Mark M Davis, Kari C Nadeau, Monica Kraft, Christian Bime, David J Erle, Mark A Atkinson, Scott C Brakenridge, Lauren I R Ehrlich, Ruth R Montgomery, Albert C Shaw, Catherine L Hough, David A Hafler, Alison D Augustine, Patrice M Becker, Bjoern Peters, Al Ozonoff, Annmarie Hoch, Seunghee Kim-Schulze, Florian Krammer, Steven Bosinger, Walter Eckalbar, Matthew C Altman, Michael Wilson, Leying Guan, Holden Maecker, Hanno Steen, Joann Diray-Arce, Nadine Rouphael … and 6 other authors
Affiliations
- Chan Zuckerberg Biohub San Francisco, San Francisco, CA, USA.
- University of Texas at Austin, Austin, TX, USA.
- University of California San Francisco, San Francisco, CA, USA.
- University of California Los Angeles, Los Angeles, CA, USA.
- Baylor College of Medicine and the Center for Translational Research on Inflammatory Diseases, Houston, TX, USA.
- Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
- Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH, USA.
- Drexel University, Tower Health Hospital, Philadelphia, PA, USA.
- Stanford University School of Medicine, Palo Alto, CA, USA.
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- The Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Oklahoma University Health Sciences Center, Oklahoma City, OK, USA.
- Oregon Health and Science University, Portland, OR, USA.
- University of Arizona, Tucson, AZ, USA.
- University of Florida, Gainesville, FL, USA.
- Yale School of Medicine, New Haven, CT, USA.
- Broad Institute of MIT and Harvard, Cambridge, MA, USA.
- National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD, USA.
- La Jolla Institute for Immunology, La Jolla, CA, USA.
- Precision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
- Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
- Clinical and Data Coordinating Center (CDCC) Precision Vaccines Program, Boston Children's Hospital, Boston, MA, USA.
- Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Ignaz Semmelweis Institute, Interuniversity Institute for Infection Research, Medical University of Vienna, Vienna, Austria.
- Ludwig Boltzmann Institute for Science Outreach and Pandemic Preparedness at the Medical University of Vienna, Vienna, Austria.
- Emory School of Medicine, Atlanta, GA, USA.
- Benaroya Research Institute, University of Washington, Seattle, WA, USA.
- Yale School of Public Health, New Haven, CT, USA.
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.
MeSH
Genes, Covid-19, Azithromycin, Gene Expression