Prophylactic azithromycin in protracted bacterial bronchitis: parental experience and impact on bacterial resistance and the microbiome

Introduction:
Protracted bacterial bronchitis (PBB) commonly underlies childhood chronic wet cough. Azithromycin prophylaxis is increasingly used to reduce exacerbations. We aimed to explore parental experience of having a child prescribed long-term antibiotics and investigate the impact of azithromycin prophylaxis on antimicrobial resistance and the nasopharyngeal microbiome.
Methods:
Fifteen parents of children prescribed prophylactic antibiotics for respiratory infections were interviewed. Thematic analysis was carried out.
Antimicrobial resistance and the microbiome were investigated by deep nasopharyngeal swabbing of children with PBB who were prescribed prophylactic azithromycin or not on clinical grounds. Protocols were optimised in an initial feasibility study. In total, 50 children were enrolled - 25 were planned to take azithromycin over the winter months and 25 were not. Serial nasopharyngeal swabs were collected over the study periods (12-20 months). Bacterial isolates were tested for antibiotic resistance and resistant isolates sequenced. 16s PCR was performed on a subset of samples.
Results:
From parental interviews key themes emerged, and a behavioural model to explain the parental experience developed. Parents desire their children to be well now, with antimicrobial resistance regarded as a possible future problem.
Higher than expected rates of azithromycin resistance were found in both PBB groups, although the resistance was mostly low level. Resistance was mostly driven by azithromycin-resistant S. pneumoniae, yet these isolates were predominantly erythromycin susceptible. There was a trend towards fewer resistant bacteria in the azithromycin group, IRR 0.63 (95%CI 0.37-1.06), p=0.083.
Alpha diversity was reduced in swabs from children taking azithromycin at the time of swab collection, p=0.02. Beta diversity was significantly different between the 2 groups at the study end; R2=0.14, p=0.0049.
Conclusions:
A holistic approach should be taken when prescribing long-term antibiotics. Discrepancies between erythromycin and azithromycin susceptibility require further investigation. Azithromycin for PBB did not promote antimicrobial resistance over the course of the study but did perturb the microbiome.