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Geographic spillover of antimicrobial resistance from mass distribution of azithromycin

Ariktha Srivathsan1,2, Ahmed M Arzika3, Ramatou Maliki3

  • 1Francis I Proctor Foundation, University of California San Francisco, San Francisco, USA.

Nature Communications
|January 29, 2026
PubMed

Insights

Mass drug administration of azithromycin reduces childhood mortality but can increase antimicrobial resistance (AMR). This study found no evidence of azithromycin-induced macrolide resistance spreading to untreated villages in Niger.

Area of Science:

  • Global Health
  • Infectious Diseases
  • Microbiology

Background:

  • Mass drug administration (MDA) with azithromycin significantly reduces childhood mortality in sub-Saharan Africa.
  • MDA with azithromycin is associated with increased antimicrobial resistance (AMR), particularly macrolide resistance.
  • Potential geographic spillover of AMR to untreated populations could impact trial risk assessments.

Purpose of the Study:

  • To investigate geographic spillover effects of genotypic macrolide resistance following azithromycin MDA.
  • To assess if AMR developed in treated areas spreads to neighboring untreated communities.

Main Methods:

  • Metagenomic deep sequencing of rectal swabs from children in Niger.
  • Analysis of 300 children in 30 monitoring villages after two years of MDA in surrounding villages.
  • Conditional permutation tests to assess associations between azithromycin treatment intensity and resistance gene abundance.

Main Results:

  • No evidence of geographic spillover of macrolide resistance was detected in untreated villages.
  • The genetic load of AMR remained at baseline levels in placebo-treated villages, irrespective of surrounding azithromycin treatment intensity.
  • Sensitivity analyses confirmed no spillover effects for other antibiotic classes.

Conclusions:

  • Azithromycin MDA-induced macrolide resistance appears localized to treated villages.
  • Concerns regarding the geographic spillover of AMR to nearby untreated villages were mitigated at 24 months.
  • Findings suggest that localized AMR effects do not significantly impact untreated populations in the study setting.

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