Related Experiment Video
Updated: Dec 1, 2025
High Throughput, Real-time, Dual-readout Testing of Intracellular Antimicrobial Activity and Eukaryotic Cell Cytotoxicity
Published on: November 16, 2016
Macrolide and Nonmacrolide Resistance with Mass Azithromycin Distribution
Thuy Doan1, Lee Worden1, Armin Hinterwirth1
1From the Francis I. Proctor Foundation (T.D., L.W., A.H., L.Z., C. Chen, C. Cook, E.L., K.S.O., C.E.O., T.C.P., J.D.K., T.M.L.), the Departments of Ophthalmology (T.D., C.E.O., T.C.P., J.D.K., T.M.L.), Epidemiology and Biostatistics (C.E.O., T.C.P., T.M.L.), and Biochemistry and Biophysics (E.D.C.), and the Institute for Global Health Sciences (T.M.L.), University of California, San Francisco, San Francisco; the Carter Center (A.M.A., R.M.), the Ministry of Health (A.A.), and the Programme National de Santé Oculaire (A.A.), Niamey, Niger; and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston (M.L.).
Background:
Mass distribution of azithromycin to preschool children twice yearly for 2 years has been shown to reduce childhood mortality in sub-Saharan Africa but at the cost of amplifying macrolide resistance. The effects on the gut resistome, a reservoir of antimicrobial resistance genes in the body, of twice-yearly administration of azithromycin for a longer period are unclear.
Methods:
We investigated the gut resistome of children after they received twice-yearly distributions of azithromycin for 4 years. In the Niger site of the MORDOR trial, we enrolled 30 villages in a concurrent trial in which they were randomly assigned to receive mass distribution of either azithromycin or placebo, offered to all children 1 to 59 months of age every 6 months for 4 years. Rectal swabs were collected at baseline, 36 months, and 48 months for analysis of the participants' gut resistome. The primary outcome was the ratio of macrolide-resistance determinants in the azithromycin group to those in the placebo group at 48 months.
Results:
Over the entire 48-month period, the mean (±SD) coverage was 86.6±12% in the villages that received placebo and 83.2±16.4% in the villages that received azithromycin. A total of 3232 samples were collected during the entire trial period; of the samples obtained at the 48-month monitoring visit, 546 samples from 15 villages that received placebo and 504 from 14 villages that received azithromycin were analyzed. Determinants of macrolide resistance were higher in the azithromycin group than in the placebo group: 7.4 times as high (95% confidence interval [CI], 4.0 to 16.7) at 36 months and 7.5 times as high (95% CI, 3.8 to 23.1) at 48 months. Continued mass azithromycin distributions also selected for determinants of nonmacrolide resistance, including resistance to beta-lactam antibiotics, an antibiotic class prescribed frequently in this region of Africa.
Conclusions:
Among villages assigned to receive mass distributions of azithromycin or placebo twice yearly for 4 years, antibiotic resistance was more common in the villages that received azithromycin than in those that received placebo. This trial showed that mass azithromycin distributions may propagate antibiotic resistance. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02047981.).
Insights
Mass azithromycin distributions in African children reduced mortality but amplified antibiotic resistance. Four years of treatment significantly increased macrolide and non-macrolide resistance determinants in the gut resistome.
Area of Science:
- Antimicrobial resistance
- Public health interventions
- Microbiome research
Background:
- Mass azithromycin distribution in sub-Saharan Africa reduces childhood mortality.
- However, this intervention increases macrolide resistance.
- Long-term effects on the gut resistome remain unclear.
Purpose of the Study:
- To investigate the impact of 4 years of mass azithromycin distribution on the gut resistome in children.
- To quantify macrolide resistance determinants in children receiving azithromycin versus placebo.
Main Methods:
- A randomized controlled trial in Niger involving 30 villages.
- Children aged 1-59 months received mass azithromycin or placebo every 6 months for 4 years.
- Rectal swabs analyzed for gut resistome at baseline, 36, and 48 months.
Main Results:
- High coverage achieved in both azithromycin (83.2%) and placebo (86.6%) groups.
- Macrolide resistance determinants were 7.5 times higher in the azithromycin group at 48 months.
- Resistance to non-macrolide antibiotics, including beta-lactams, also increased.
Conclusions:
- Four years of mass azithromycin distribution led to increased antibiotic resistance.
- The findings suggest mass azithromycin distribution may propagate antibiotic resistance.
- This highlights a critical trade-off between reducing mortality and increasing antimicrobial resistance.
More Related Videos
Related Concept Videos
01:30Development of Antibiotic Resistance
00:57Antibiotic Selection