@article{Mac:2024:10.1164/rccm.202306-1059OC,
author = {Mac, Aogáin M and Xaverius, Ivan F and Jaggi, TK and Richardson, H and Shoemark, A and Narayana, JK and Dicker, AJ and Koh, MS and Lee, KCH and Thun, How O and Poh, ME and Chin, KK and Hou, ALY and Ser, Hon P and Low, TB and Abisheganaden, JA and Dimakou, K and Digalaki, A and Kosti, C and Gkousiou, A and Hansbro, PM and Blasi, F and Aliberti, S and Chalmers, JD and Chotirmall, SH},
doi = {10.1164/rccm.202306-1059OC},
journal = {Am J Respir Crit Care Med},
pages = {47--62},
title = {Airway "Resistotypes" and Clinical Outcomes in Bronchiectasis.},
url = {http://dx.doi.org/10.1164/rccm.202306-1059OC},
volume = {210},
year = {2024}
}

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TY  - JOUR
AB  - Rationale: Chronic infection and inflammation shapes the airway microbiome in bronchiectasis. Utilizing whole-genome shotgun metagenomics to analyze the airway resistome provides insight into interplay between microbes, resistance genes, and clinical outcomes. Objectives: To apply whole-genome shotgun metagenomics to the airway microbiome in bronchiectasis to highlight a diverse pool of antimicrobial resistance genes: the "resistome," the clinical significance of which remains unclear. Methods: Individuals with bronchiectasis were prospectively recruited into cross-sectional and longitudinal cohorts (n = 280), including the international multicenter cross-sectional Cohort of Asian and Matched European Bronchiectasis 2 (CAMEB 2) study (n = 251) and two independent cohorts, one describing patients experiencing acute exacerbation and a further cohort of patients undergoing Pseudomonas aeruginosa eradication treatment. Sputum was subjected to metagenomic sequencing, and the bronchiectasis resistome was evaluated in association with clinical outcomes and underlying host microbiomes. Measurements and Main Results: The bronchiectasis resistome features a unique resistance gene profile and increased counts of aminoglycoside, bicyclomycin, phenicol, triclosan, and multidrug resistance genes. Longitudinally, it exhibits within-patient stability over time and during exacerbations despite between-patient heterogeneity. Proportional differences in baseline resistome profiles, including increased macrolide and multidrug resistance genes, associate with shorter intervals to the next exacerbation, whereas distinct resistome archetypes associate with frequent exacerbations, poorer lung function, geographic origin, and the host microbiome. Unsupervised analysis of resistome profiles identified two clinically relevant "resistotypes," RT1 and RT2, the latter characterized by poor clinical outcomes, increased multidrug resistance, and P. a
AU  - Mac,Aogáin M
AU  - Xaverius,Ivan F
AU  - Jaggi,TK
AU  - Richardson,H
AU  - Shoemark,A
AU  - Narayana,JK
AU  - Dicker,AJ
AU  - Koh,MS
AU  - Lee,KCH
AU  - Thun,How O
AU  - Poh,ME
AU  - Chin,KK
AU  - Hou,ALY
AU  - Ser,Hon P
AU  - Low,TB
AU  - Abisheganaden,JA
AU  - Dimakou,K
AU  - Digalaki,A
AU  - Kosti,C
AU  - Gkousiou,A
AU  - Hansbro,PM
AU  - Blasi,F
AU  - Aliberti,S
AU  - Chalmers,JD
AU  - Chotirmall,SH
DO  - 10.1164/rccm.202306-1059OC
EP  - 62
PY  - 2024///
SP  - 47
TI  - Airway "Resistotypes" and Clinical Outcomes in Bronchiectasis.
T2  - Am J Respir Crit Care Med
UR  - http://dx.doi.org/10.1164/rccm.202306-1059OC
UR  - https://www.ncbi.nlm.nih.gov/pubmed/38271608
VL  - 210
ER  - 

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