The antibiotic resistance reservoir of the lung microbiome expands with age in a population of critically ill patients

Victoria T. Chu, Alexandra Tsitsiklis, Eran Mick, Lilliam Ambroggio, Katrina L. Kalantar, Abigail Glascock, Christina M. Osborne, Brandie D. Wagner, Michael A. Matthay, Joseph L. DeRisi, Carolyn S. Calfee, Peter M. Mourani and Charles R. Langelier ()
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Victoria T. Chu: University of California
Alexandra Tsitsiklis: University of California
Eran Mick: University of California
Lilliam Ambroggio: University of Colorado and Children’s Hospital Colorado
Katrina L. Kalantar: Chan Zuckerberg Initiative
Abigail Glascock: Chan Zuckerberg Biohub
Christina M. Osborne: University of Colorado and Children’s Hospital Colorado
Brandie D. Wagner: University of Colorado and Children’s Hospital Colorado
Michael A. Matthay: Cardiovascular Research Institute, University of California
Joseph L. DeRisi: Chan Zuckerberg Biohub
Carolyn S. Calfee: Cardiovascular Research Institute, University of California
Peter M. Mourani: Arkansas Children’s Hospital
Charles R. Langelier: University of California

Nature Communications, 2024, vol. 15, issue 1, 1-10

Abstract: Abstract Antimicrobial resistant lower respiratory tract infections are an increasing public health threat and an important cause of global mortality. The lung microbiome can influence susceptibility of respiratory tract infections and represents an important reservoir for exchange of antimicrobial resistance genes. Studies of the gut microbiome have found an association between age and increasing antimicrobial resistance gene burden, however, corollary studies in the lung microbiome remain absent. We performed an observational study of children and adults with acute respiratory failure admitted to the intensive care unit. From tracheal aspirate RNA sequencing data, we evaluated age-related differences in detectable antimicrobial resistance gene expression in the lung microbiome. Using a multivariable logistic regression model, we find that detection of antimicrobial resistance gene expression was significantly higher in adults compared with children after adjusting for demographic and clinical characteristics. This association remained significant after additionally adjusting for lung bacterial microbiome characteristics, and when modeling age as a continuous variable. The proportion of adults expressing beta-lactam, aminoglycoside, and tetracycline antimicrobial resistance genes was higher compared to children. Together, these findings shape our understanding of the lung resistome in critically ill patients across the lifespan, which may have implications for clinical management and global public health.

Date: 2024
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DOI: 10.1038/s41467-023-44353-1

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