Impact of prophylactic and ‘rescue pack’ antibiotics on the airway microbiome in chronic lung disease

The management of many chronic lung diseases involves multiple antibiotic prescriptions either to treat acute exacerbations or as prophylactic therapy to reduce the frequency of exacerbations and improve patients’ quality of life. Aim To investigate the effects of antibiotics on the homeostasis of bacterial communities in the airways, and how this may contribute to antimicrobial resistance (AMR) among respiratory pathogens and microbiota. Methods Within an observational cohort study, sputum was collected from 84 patients with chronic obstructive pulmonary disease and/or bronchiectasis at stable state: 47 were receiving antibiotic prophylaxis therapy. V3-V4 16S-rRNA sequencing on Illumina MiSeq, quantitative PCR for typical respiratory pathogens, bacteriology cultures and antimicrobial susceptibility testing of sputum isolates, resistome analysis on a subset of 17 sputum samples using MinION metagenomics sequencing were performed. Finding The phylogenetic α-diversity and the total bacterial density in sputum were significantly lower in patients receiving prophylactic antibiotics (p=0.014 and 0.029, respectively). Antibiotic prophylaxis was associated with significantly lower relative abundance of respiratory pathogens such as Pseudomonas aeruginosa , Moraxella catarrhalis and members of family Enterobacteriaceae in the airway microbiome, but not Haemophilus influenzae and Streptococcus pneumoniae . No major definite directional shifts in the microbiota composition were identified with prophylactic antibiotic use at the cohort level. Surveillance of AMR and resistome analysis revealed a high frequency of resistance to macrolide and tetracycline in the cohort. AMR expressed by pathogenic bacterial isolates was associated with antibiotics prescribed as ‘rescue packs’ for prompt initiation of self-treatment of exacerbations (Spearman’s rho=0.408, p=0.02). Conclusions Antibiotic prophylactic therapy suppresses recognised pathogenic bacteria in the sputum of patients with chronic lung disease. The use of antibiotic rescue packs may be driving AMR in this cohort rather than prophylactic antibiotics.