International epidemiology of antimicrobial resistance in people living with chronic lung infection.

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 were analysed from 110 323 respiratory samples in 19 143 individuals with bronchiectasis or CF across 11 cities, eight countries, three continents between 2011 and 2024. Longitudinal AMR prevalence, multidrug-resistant (MDR) and extensively drug-resistant (XDR) prevalence and multiple antibiotic resistance (MAR) index were 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%; bronchiectasis: MDR 13.4%; XDR 1.5%). A longitudinal rise in P. aeruginosa AMR was seen in bronchiectasis across four centres for antipseudomonal aminoglycosides (p<0.001; OR/year 1.44; 95% CI 1.24 to 1.67), fluoroquinolones (p=0.002; OR/year 1.13; 95% CI 1.05 to 1.23), cephalosporins (p=0.005; OR/year 1.17; 95% CI 1.05 to 1.30), penicillins with beta-lactamase inhibitor (p=0.02; OR/year 1.18; 95% CI 1.03 to 1.35) and carbapenems (p=0.048; OR/year 1.11; 95% CI 1.00 to 1.23). Rising longitudinal K. pneumoniae AMR was seen for cephalosporins (p=0.01; OR/year 1.32; 95% CI 1.06 to 1.65) and carbapenems (p=0.04; OR/year 1.64; 95% CI 1.03 to 2.62). A significant increase in AMR, as measured by the MAR index, was observed in individuals with residual culture-positive CF receiving triple cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy (p<0.001). Strong concurrent resistance was noted in bronchiectasis across regions with geographic variation in disjoint antimicrobial pair resistance.

Conclusion: We show a significant increasing international AMR burden in bronchiectasis and CF, with geographic variation and persistence post-CFTR modulator therapy.