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Published on: November 17, 2018
Effect of Biannual Azithromycin Distribution to Infants on Community Gut Resistome and Microbiome: A
Boubacar Coulibaly1, Daisy Yan2, Ali Sié1
1Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso.
Insights
Targeted biannual azithromycin (antibiotic resistance) administration in infants did not increase gut antibiotic resistance or alter microbiomes in young children. This approach aligns with WHO guidelines for reducing childhood mortality while minimizing resistance selection.
Area of Science:
- Global Health
- Infectious Diseases
- Microbiology
Background:
- Biannual azithromycin in sub-Saharan Africa reduced childhood mortality but raised antibiotic resistance (AMR) concerns.
- World Health Organization (WHO) guidelines suggest targeting infants (1-11 months) to balance mortality reduction and AMR selection.
- The Infant Mortality Reduction by the Mass Administration of Azithromycin (IMMI) study evaluated these WHO guidelines.
Purpose of the Study:
- To investigate the impact of targeted biannual azithromycin administration to infants on community-level antibiotic resistance.
- To assess changes in gut microbiome structure and diversity following infant-targeted azithromycin treatment.
Main Methods:
- A double-masked, placebo-controlled, cluster-randomized trial in Burkina Faso involving 60 communities.
- Randomized health centers to biannual azithromycin (67%) or placebo (33%) for infants aged 1-11 months.
- Analyzed 3,524 rectal samples from children aged 1-59 months for macrolide resistance determinants and microbiome composition.
Main Results:
- No significant increase in macrolide resistance determinants was observed in communities receiving azithromycin compared to placebo (1.05-fold change).
- Fold changes for other resistance determinants (beta-lactams, metronidazole, sulfonamides, tetracycline, trimethoprim) were also minimal.
- No detectable differences in microbiome structure or Shannon diversity index were found between treatment arms 6 months after the fourth dose.
Conclusions:
- Targeted biannual azithromycin administration to infants (1-11 months) did not result in significant long-lasting increases in gut antibiotic resistance.
- The intervention did not lead to substantial alterations in the gut microbiomes of children aged 1-59 months.
- Findings support WHO guidelines for using azithromycin in young children to reduce mortality while mitigating AMR selection pressure.
Abstract:
Biannual azithromycin administration to preschool children in sub-Saharan Africa improved childhood mortality but selected for antibiotic resistance (AMR). WHO guidelines recommended focusing treatment on infants ages 1-11 months old to reduce mortality while minimizing selection of AMR. The Infant Mortality Reduction by the Mass Administration of Azithromycin study was a double-masked, placebo-controlled, cluster-randomized trial that investigated these WHO guidelines. Health centers from three regions of Burkina Faso were randomized in a 2:1 ratio to receive either biannual azithromycin (67%) or placebo (33%) distribution to children 1-11 months old. A total of 3,524 rectal samples from children ages 1-59 months old from 60 randomly selected communities were included in the analysis. The prespecified primary outcome was the community-level fold change in macrolide resistance determinants between arms at the 24-month time point. Macrolide resistance determinants in the gut of children in communities whose infants received azithromycin did not increase compared with those in communities treated with placebo (1.05-fold change). Similarly, the fold changes for resistance determinants for beta-lactams, metronidazole, sulfonamides, tetracycline, and trimethoprim were 0.99-fold, 1.00-fold, 1.22-fold, 0.96-fold, and 0.96-fold, respectively. At 6 months after the fourth treatment, there were no detectable differences in the microbiome structure (Euclidean permutational multivariate analysis of variance) and Shannon diversity index between treatment arms. These results suggest that biannual azithromycin administration to children 1-11 months old did not lead to a significant long-lasting increase in gut AMR or alterations of the gut microbiomes of children 1-59 months old in the community.
