Antibiotic Selection Pressure Causally Linked to Macrolide Resistome
Communities randomly assigned to less frequent antibiotic use had significantly lower prevalence of genetic antibiotic resistance determinants.
Communities randomly assigned to less frequent antibiotic use had a significantly lower prevalence of genetic antibiotic resistance determinants, according to a cluster randomized trial published in Clinical Infectious Diseases.
The trial randomly assigned 24 communities to either annual or biannual mass azithromycin distributions for trachoma (ClinicalTrials.gov Identifier: NCT00792922). In the trial, 2 genetic determinants of macrolide resistance were identified from swabs of 120 randomly sampled preschool children before mass treatment and another 120 children to 2 years post-treatment.
Before treatment, both communities (annual treatment communities n=12; biannual treatment communities n=12) had similar rates of both genetic resistance determinants. Median prevalence was 20% (interquartile range [IQR], 10% to 40%) in each group.
After 24 months of mass treatment, the macrolide resistance determinants were more common in the biannually treated communities, with a median prevalence of 60% (IQR, 50% to 80%) compared with median a prevalence of 40% (IQR, 20% to 40%; P <.001) in the annually treated communities.
After adjusting for baseline, the 24-month prevalence in the biannual group was 29.4% higher (95% CI, 10.5% to 56.7%).
The study was conducted in Niger in communities that received mass azithromycin distributions prior to the study, which affected the generalizability of the results. The sample sizes were also small and non-study antibiotic consumption was unknown, as was the impact of resistance determinants on respiratory infections in the study communities.
However, the investigators highlight that the key finding is “the causal and cumulative exposure-dependent relationship between antibiotic selection pressure and community antibiotic resistance.”
They also validated the resistome approach and believe the results “suggest that reducing levels of antibiotic consumption in a population is an effective method for reducing the community prevalence of antibiotic resistance.”
Keenan J, Chin S, Amza A, et al. The effect of antibiotic selection pressure on the nasopharyngeal macrolide resistome: a cluster-randomized trial [published online April 20 2018]. Clin Infect Dis. doi:10.1093/cid/ciy339