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Author Spotlight: Understanding and Detecting Environmental Antimicrobial Resistance by Combining Culture-Based Techniques and Genomics
Published on: July 19, 2024
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, USA.
Abstract:
Large-scale, placebo-controlled, cluster-randomized trials in high-mortality settings in several African countries demonstrated a 14-18% reduction in childhood mortality following twice-annual mass drug administration (MDA) of azithromycin among children aged 1-59 months [1-3]. Azithromycin MDA also selects for antimicrobial resistance (AMR), particularly macrolide resistance in treated populations [4-6]. It is unknown whether the genetic selection of AMR from azithromycin MDA could spill over to neighboring untreated populations. If present, such geographic spillover effects could lead the trials to underestimate the risks of AMR selection from azithromycin MDA. Here, we assessed between-village geographic spillover effects of genotypic resistance to macrolides and other antibiotic classes in rectal swabs collected from 1200 children in 30 monitoring villages in Niger after two years of MDA in 594 surrounding villages. We found no evidence of geographic spillover of macrolide resistance in untreated villages, as the genetic load of AMR remained at baseline levels in placebo-treated villages regardless of surrounding azithromycin treatment intensity. Sensitivity analyses confirmed the robustness of findings to the metric used to quantify the effect of proximal azithromycin MDAs on macrolide AMR, and no geographic spillover effects were detected for AMR to other antibiotic classes. Our results suggest that azithromycin MDA-induced selection of macrolide AMR is localized to treated villages without extending to children in neighboring, untreated villages, mitigating some concerns about geographic spillover of AMR to untreated populations. This analysis illustrates the value of randomized trial designs in assessing indirect effects of large-scale public health interventions.
Insights
Mass drug administration of azithromycin reduces childhood mortality but can increase antimicrobial resistance (AMR). This study found no geographic spillover of macrolide resistance to untreated villages, suggesting localized AMR selection from azithromycin interventions.
Area of Science:
- Global Health
- Infectious Diseases
- Microbiology
Background:
- Mass drug administration (MDA) of azithromycin significantly reduces childhood mortality in high-mortality regions.
- Azithromycin MDA is associated with the selection of antimicrobial resistance (AMR), particularly macrolide resistance.
- Potential geographic spillover of AMR from treated to untreated populations remains an unaddressed concern.
Purpose of the Study:
- To investigate geographic spillover effects of genotypic macrolide resistance from azithromycin mass drug administration (MDA) to neighboring untreated populations.
- To assess if azithromycin MDA influences antimicrobial resistance (AMR) in antibiotic classes beyond macrolides in untreated communities.
Main Methods:
- A cluster-randomized trial design was employed in Niger, involving 1200 children across 30 monitoring villages.
- Rectal swabs were collected after two years of MDA in 594 surrounding villages to assess genotypic resistance.
- Genotypic resistance to macrolides and other antibiotic classes was analyzed in treated and untreated (placebo) villages.
Main Results:
- No evidence of geographic spillover of macrolide resistance was detected in untreated villages.
- The genetic load of antimicrobial resistance (AMR) in placebo-treated villages remained at baseline levels, irrespective of surrounding azithromycin MDA intensity.
- Sensitivity analyses confirmed that azithromycin MDA's effect on macrolide AMR is localized, with no spillover to other antibiotic classes observed.
Conclusions:
- Azithromycin MDA-induced selection of macrolide antimicrobial resistance (AMR) is geographically localized to treated villages.
- Concerns regarding the geographic spillover of AMR to untreated populations are mitigated by these findings.
- Randomized trial designs are valuable for evaluating indirect effects of public health interventions like mass drug administration.
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