International epidemiology of antimicrobial resistance in people living with chronic lung infection
File(s)
Accepted version
Author(s)
Shah, Anand
Type
Journal Article
Abstract
Background: Antimicrobial resistance (AMR) is a global threat for people with chronic lung infection, however international AMR epidemiology in bronchiectasis and Cystic Fibrosis (CF) is poorly characterised. In this study we retrospectively analyse international longitudinal
AMR epidemiology in bronchiectasis and CF.
Methods: Microbiology data was analysed from 110323 respiratory samples in 19143 individuals with bronchiectasis or CF across 11 cities, 8 countries, 3 continents between 2011-2024. Longitudinal AMR prevalence, multi-drug and extensive-drug resistance (MDR,XDR) and multiple antibiotic resistance (MAR) index was analysed by disease and country. Pilot analysis of concurrent/disjoint resistance in antimicrobial pairs and triplets in regional datasets was performed to inform combination or cyclical antimicrobial choice.
Findings: Geographic AMR differences were noted across pathogens in bronchiectasis and CF with increased Pseudomonas aeruginosa resistance in central/southern Europe and increased Klebsiella pneumoniae resistance in Hong Kong. MDR burden was high in emergent pathogens Escherichia coli (CF:MDR-32.6%;XDR-12.4%; Bronchiectasis:MDR-39.2%;XDR-4.9%) and K.pneumoniae (CF:MDR-22.7%;XDR-15.6%;
A longitudinal rise in P.aeruginosa AMR was seen in bronchiectasis across 4 centres for anti
pseudomonal aminoglycosides (p=<0.001;OR/yr:1.44;(95%CI:1.24-1.67)), fluoroquinolones
(p=0.002;OR/yr:1.13;(95%CI:1.05-1.23)), cephalosporins (p=0.005;OR/yr:1.17;(95%CI:1.05
1.30)), penicillins with beta-lactamase inhibitor (p=0.02;OR/yr:1.18;(95%CI:1.03-1.35)) and
carbapenems (p=0.048;OR/yr:1.11;(95%CI:1.00-1.23)). Rising longitudinal K.pneumoniae
AMR was seen for cephalosporins (p=0.01;OR/yr:1.32;(95%CI:1.06-1.65)) and carbapenems
(p=0.04;OR/yr:1.64;(95%CI:1.03-2.62)). Significant increased AMR by MAR index was seen in
residual culture-positive CF individuals on triple CFTR modulator therapy (p<0.001). Strong
concurrent resistance was noted in bronchiectasis across regions with geographic variation in
disjoint antimicrobial pair resistance.
Bronchiectasis:MDR-13.4%;XDR-1.5%).
Conclusion: We show significant increasing international AMR burden in bronchiectasis and CF with geographic variation and persistence post CFTR modulator therapy.
Funding: AMR-Lung is a Clinical Research Collaborative
funded by the European Respiratory Society.
What is already known on this topic – Despite people living with bronchiectasis and cystic fibrosis being particularly vulnerable to antimicrobial resistance given repeated and prolonged antibiotic exposure to date there has been no international analysis of AMR burden
or dynamics in these groups.
What this study adds - In this multinational retrospective study we show substantial geographic variation in pathogen prevalence and high AMR burden in both bronchiectasis and cystic fibrosis, temporal increases in resistance to key antibiotic classes and persistent AMR
burden among people receiving CFTR modulators.
AMR epidemiology in bronchiectasis and CF.
Methods: Microbiology data was analysed from 110323 respiratory samples in 19143 individuals with bronchiectasis or CF across 11 cities, 8 countries, 3 continents between 2011-2024. Longitudinal AMR prevalence, multi-drug and extensive-drug resistance (MDR,XDR) and multiple antibiotic resistance (MAR) index was analysed by disease and country. Pilot analysis of concurrent/disjoint resistance in antimicrobial pairs and triplets in regional datasets was performed to inform combination or cyclical antimicrobial choice.
Findings: Geographic AMR differences were noted across pathogens in bronchiectasis and CF with increased Pseudomonas aeruginosa resistance in central/southern Europe and increased Klebsiella pneumoniae resistance in Hong Kong. MDR burden was high in emergent pathogens Escherichia coli (CF:MDR-32.6%;XDR-12.4%; Bronchiectasis:MDR-39.2%;XDR-4.9%) and K.pneumoniae (CF:MDR-22.7%;XDR-15.6%;
A longitudinal rise in P.aeruginosa AMR was seen in bronchiectasis across 4 centres for anti
pseudomonal aminoglycosides (p=<0.001;OR/yr:1.44;(95%CI:1.24-1.67)), fluoroquinolones
(p=0.002;OR/yr:1.13;(95%CI:1.05-1.23)), cephalosporins (p=0.005;OR/yr:1.17;(95%CI:1.05
1.30)), penicillins with beta-lactamase inhibitor (p=0.02;OR/yr:1.18;(95%CI:1.03-1.35)) and
carbapenems (p=0.048;OR/yr:1.11;(95%CI:1.00-1.23)). Rising longitudinal K.pneumoniae
AMR was seen for cephalosporins (p=0.01;OR/yr:1.32;(95%CI:1.06-1.65)) and carbapenems
(p=0.04;OR/yr:1.64;(95%CI:1.03-2.62)). Significant increased AMR by MAR index was seen in
residual culture-positive CF individuals on triple CFTR modulator therapy (p<0.001). Strong
concurrent resistance was noted in bronchiectasis across regions with geographic variation in
disjoint antimicrobial pair resistance.
Bronchiectasis:MDR-13.4%;XDR-1.5%).
Conclusion: We show significant increasing international AMR burden in bronchiectasis and CF with geographic variation and persistence post CFTR modulator therapy.
Funding: AMR-Lung is a Clinical Research Collaborative
funded by the European Respiratory Society.
What is already known on this topic – Despite people living with bronchiectasis and cystic fibrosis being particularly vulnerable to antimicrobial resistance given repeated and prolonged antibiotic exposure to date there has been no international analysis of AMR burden
or dynamics in these groups.
What this study adds - In this multinational retrospective study we show substantial geographic variation in pathogen prevalence and high AMR burden in both bronchiectasis and cystic fibrosis, temporal increases in resistance to key antibiotic classes and persistent AMR
burden among people receiving CFTR modulators.
Date Acceptance
2026-08-21
Citation
Thorax
ISSN
0040-6376
Publisher
BMJ Publishing Group
Journal / Book Title
Thorax
Copyright Statement
Copyright This paper is embargoed until publication. Once published the Version of Record (VoR) will be available on immediate open access.
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Publication Status
Accepted