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

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2026年3月16日

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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,
Steven M. Holland,
Lindsey B. Rosen,
Serena Lee,
Tatyana Vaysman,
Al Ozonoff,
Joann Diray-Arce,
Jing Chen,
Alvin Kho,
Carly E. Milliren,
Ana C. Chang,
Kerry McEnaney,
Brenda Barton,
Claudia Lentucci,
Maimouna D. Murphy,
Mehmet Saluvan,
Tanzia Shaheen,
Shanshan Liu,
Caitlin Syphurs,
Marisa Albert,
Arash Nemati Hayati,
Robert Bryant,
James Abraham,
Sanya Thomas,
Mitchell Cooney,
Meagan Karoly,
Scott Presnell,
Bernard Kohr,
Tomasz Jancsyk,
Azlann Arnett,
James A. Overton,
Randi Vita,
Kerstin Westendorf,
Ofer Levy,
Hanno Steen,
Patrick van Zalm,
Benoit Fatou,
Kinga K. Smolen,
Arthur Viode,
Simon van Haren,
Meenakshi Jha,
David Stevenson,
Oludare Odumade,
Kevin Mendez,
Jessica Lasky-Su,
Alexandra Tong,
Rebecca Rooks,
Michael Desjardins,
Amy C. Sherman,
Stephen R. Walsh,
Xhoi Mitre,
Jessica Cauley,
Xiofang Li,
Bethany Evans,
Christina Montesano,
Jose Humberto Licona,
Jonathan Krauss,
Nicholas C. Issa,
Jun Bai Park Chang,
Natalie Izaguirre,
Scott R. Hutton,
Greg Michelotti,
Kari Wong,
Scott J. Tebbutt,
Casey P. Shannon,
Rafick-Pierre Sekaly,
Slim Fourati,
Paul Harris,
Scott Sieg,
Susan Pereira Ribeiro,
Michele A. Kutzler,
Mariana Bernui,
Gina Cusimano,
Jennifer Connors,
Kyra Woloszczuk,
David Joyner,
Carolyn Edwards,
Edward Lee,
Edward Lin,
Nataliya Melnyk,
Debra L. Powell,
James N. Kim,
I. Michael Goonewardene,
Brent Simmons,
Cecilia M. Smith,
Mark Martens,
Brett Croen,
Nicholas C. Semenza,
Mathew R. Bell,
Sara Furukawa,
Renee McLin,
George P. Tegos,
Brandon Rogowski,
Nathan Mege,
Kristen Ulring,
Pam Schearer,
Judie Sheidy,
Crystal Nagle,
Vicki Seyfert-Margolis,
Steven E. Bosinger,
Arun K. Boddapati,
Greg K. Tharp,
Kathryn L. Pellegrini,
Brandi Johnson,
Bernadine Panganiban,
Christopher Huerta,
Evan J. Anderson,
Hady Samaha,
Jonathan E. Sevransky,
Laurel Bristow,
Elizabeth Beagle,
David Cowan,
Sydney Hamilton,
Thomas Hodder,
Amer Bechnak,
Andrew Cheng,
Aneesh Mehta,
Caroline R. Ciric,
Christine Spainhour,
Erin Carter,
Erin M. Scherer,
Jacob Usher,
Kieffer Hellmeister,
Laila Hussaini,
Lauren Hewitt,
Nina Mcnair,
Sonia Wimalasena,
Ana Fernandez-Sesma,
Viviana Simon,
Florian Krammer,
Harm Van Bakel,
Ana Silvia Gonzalez Reiche,
Jingjing Qi,
Brian Lee,
Juan Manuel Carreño,
Gagandeep Singh,
Ariel Raskin,
Johnstone Tcheou,
Zain Khalil,
Adriana van de Guchte,
Keith Farrugia,
Zenab Khan,
Geoffrey Kelly,
Komal Srivastava,
Lily Q. Eaker,
Maria C. Bermúdez-González,
Lubbertus C. F. Mulder,
Katherine F. Beach,
Miti Saksena,
Deena Altman,
Erna Kojic,
Levy A. Sominsky,
Arman Azad,
Dominika Bielak,
Hisaaki Kawabata,
Temima Yellin,
Miriam Fried,
Leeba Sullivan,
Sara Morris,
Giulio Kleiner,
Daniel Stadlbauer,
Jayeeta Dutta,
Hui Xie,
Manishkumar Patel,
Kai Nie,
Adeeb Rahman,
William B. Messer,
Catherine L. Hough,
Sarah A. R. Siegel,
Peter E. Sullivan,
Zhengchun Lu,
Amanda E. Brunton,
Matthew Strand,
Zoe L. Lyski,
Felicity J. Coulter,
Courtney Micheleti,
Yael Rosenberg-Hasson,
Michael Leipold,
Natalia Sigal,
Angela Rogers,
Andrea Fernandes,
Monali Manohar,
Evan Do,
Iris Chang,
Alexandra S. Lee,
Catherine Blish,
Henna Naz Din,
Jonasel Roque,
Linda Geng,
Maja Artandi,
Neera Ahuja,
Samuel S. Yang,
Sharon Chinthrajah,
Thomas Hagan,
Elaine F. Reed,
Joanna Schaenman,
Ramin Salehi-Rad,
Adreanne M. Rivera,
Harry C. Pickering,
Subha Sen,
David Elashoff,
Dawn C. Ward,
Jenny Brook,
Estefania Ramires Sanchez,
Megan Llamas,
Claudia Perdomo,
Clara E. Magyar,
Jennifer Fulcher,
Carolyn M. Hendrickson,
Kirsten N. Kangelaris,
Viet Nguyen,
Deanna Lee,
Suzanna Chak,
Rajani Ghale,
Ana Gonzalez,
Alejandra Jauregui,
Carolyn Leroux,
Luz Torres Altamirano,
Ahmad Sadeed Rashid,
Andrew Willmore,
Prescott G. Woodruff,
Matthew F. Krummel,
Sidney Carrillo,
Alyssa Ward,
Charles R. Langelier,
Ravi Patel,
Ravi Dandekar,
Bonny Alvarenga,
Jayant Rajan,
Andrew W. Schroeder,
Gabriela K. Fragiadakis,
Alexandra Tsitsiklis,
Eran Mick,
Yanedth Sanchez Guerrero,
Christina Love,
Lenka Maliskova,
Michael Adkisson,
Aleksandra Leligdowicz,
Alexander Beagle,
Arjun Rao,
Austin Sigman,
Bushra Samad,
Cindy Curiel,
Cole Shaw,
Gayelan Tietje-Ulrich,
Jeff Milush,
Jonathan Singer,
Joshua J. Vasquez,
Kevin Tang,
Legna Betancourt,
Lekshmi Santhosh,
Logan Pierce,
Maria Tecero Paz,
Michael Matthay,
Neeta Thakur,
Nicklaus Rodriguez,
Nicole Sutter,
Norman Jones,
Pratik Sinha,
Priya Prasad,
Raphael Lota,
Sadeed Rashid,
Saurabh Asthana,
Sharvari Bhide,
Tasha Lea,
Yumiko Abe-Jones,
David A. Hafler,
Steven H. Kleinstein,
Jeremy P. Gygi,
Shrikant Pawar,
Anna Konstorum,
Ernie Chen,
Chris Cotsapas,
Xiaomei Wang,
Leqi Xu,
Charles Dela Cruz,
Akiko Iwasaki,
Subhasis Mohanty,
Allison Nelson,
Yujiao Zhao,
Shelli Farhadian,
Hiromitsu Asashima,
Omkar Chaudhary,
Andreas Coppi,
John Fournier,
M. Catherine Muenker,
Khadir Raddassi,
Michael Rainone,
William Ruff,
Syim Salahuddin,
Wade L. Shulz,
Pavithra Vijayakumar,
Haowei Wang,
Esio Wunder Jr.,
H. Patrick Young,
Albert I. Ko,
Denise Esserman,
Anderson Brito,
Jessica Rothman,
Nathan D. Grubaugh,
Li-Zhen Song,
Ebony Nelson,
Lauren A. Sinko,
J. Leland Booth,
Douglas A. Drevets,
Brent R. Brown,
Christian Bime,
Jarrod Mosier,
Heidi Erickson,
Ron Schunk,
Hiroki Kimura,
Michelle Conway,
Dave Francisco,
Allyson Molzahn,
Connie Cathleen Wilson,
Trina Hughes,
Bianca Sierra,
Ricardo F. Ungaro,
Brittany Roth Manning,
Jordan Oberhaus,
Faheem W. Guirgis,
Brittney Borresen,
Matthew L. Anderson,
Lauren I. R. Ehrlich,
Esther Melamed,
Cole Maguire,
Dennis Wylie,
Justin F. Rousseau,
Kerin C. Hurley,
Janelle N. Geltman,
Nadia Siles,
Jacob E. Rogers,
Pablo Guaman Tipan,
Joann Diray-Arce,
Nadine Rouphael,
Steven H. Kleinstein,
Naresh Doni Jayavelu,
Elaine F. Reed,
Ofer Levy,
Victoria T. Chu,
Charles R. Langelier

摘要

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.