Seasonal azithromycin use in paediatric protracted bacterial bronchitis does not promote antimicrobial resistance but does modulate the nasopharyngeal microbiome

Protracted bacterial bronchitis (PBB) causes chronic wet cough for which seasonal azithromycin is increasingly used to reduce exacerbations. We investigated the impact of seasonal azithromycin on antimicrobial resistance and the nasopharyngeal microbiome. In an observational cohort study, 50 children with PBB were enrolled over two consecutive winters; 25/50 at study entry were designated on clinical grounds to take azithromycin over the winter months and 25/50 were not. Serial nasopharyngeal swabs were collected during the study period (12–20 months) and cultured bacterial isolates were assessed for antimicrobial susceptibility. 16S rRNA-based sequencing was performed on a subset of samples. Irrespective of azithromycin usage, high levels of azithromycin resistance were found; 73% of bacteria from swabs in the azithromycin group vs. 69% in the comparison group. Resistance was predominantly driven by azithromycin-resistant S. pneumoniae, yet these isolates were mostly erythromycin susceptible. Analysis of 16S rRNA-based sequencing revealed a reduction in within-sample diversity in response to azithromycin, but only in samples of children actively taking azithromycin at the time of swab collection. Actively taking azithromycin at the time of swab collection significantly contributed to dissimilarity in bacterial community composition. The discrepancy between laboratory detection of azithromycin and erythromycin resistance in the S. pneumoniae isolates requires further investigation. Seasonal azithromycin for PBB did not promote antimicrobial resistance over the study period, but did perturb the microbiome.