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Randomized Controlled Trial
. 2024 Nov 22;79(5):1136-1143.
doi: 10.1093/cid/ciae267.

Assessment of Spillover of Antimicrobial Resistance to Untreated Children 7-12 Years Old After Mass Drug Administration of Azithromycin for Child Survival in Niger: A Secondary Analysis of the MORDOR Cluster-Randomized Trial

Brittany Peterson  1   2 , Ahmed M Arzika  3 , Abdou Amza  4 , Ramatou Maliki  3 , Alio Mankara Karamba  3 , Mariama Moussa  3 , Mariama Kemago  3 , Zijun Liu  1 , Eric Houpt  5 , Jie Liu  6 , Suporn Pholwat  5 , Thuy Doan  1   7 , Travis C Porco  1   2   7   8 , Jeremy D Keenan  1   7 , Thomas M Lietman  1   2   7   8 , Kieran S O'Brien  1   2   7   8
Affiliations
Randomized Controlled Trial

Assessment of Spillover of Antimicrobial Resistance to Untreated Children 7-12 Years Old After Mass Drug Administration of Azithromycin for Child Survival in Niger: A Secondary Analysis of the MORDOR Cluster-Randomized Trial

Brittany Peterson et al. Clin Infect Dis. .

Abstract

Background: The risk of antibiotic resistance is complicated by the potential for spillover effects from one treated population to another. Azithromycin mass drug administration programs report higher rates of antibiotic resistance among treatment arms in targeted groups. This study aimed to understand the risk of spillover of antibiotic resistance to nontarget groups in these programs.

Methods: Data were used from a cluster-randomized trial comparing the effects of biannual azithromycin and placebo distribution to children 1-59 months old on child mortality rates. Nasopharyngeal samples from untreated children 7-12 years old were tested for genetic determinants of macrolide resistance (primary outcome) and resistance to other antibiotic classes (secondary outcomes). Linear regression was used to compare the community-level mean difference in prevalence by arm at the 24-month time point, adjusting for baseline prevalence.

Results: A total of 1103 children 7-12 years old in 30 communities were included in the analysis (15 azithromycin, 15 placebo). The adjusted mean differences in the prevalence of resistance determinants for macrolides, β-lactams, and tetracyclines were 3.4% (95% confidence interval, -4.1% to 10.8%; P = .37), -1.2% (-7.9% to 5.5%; P = .72), and -3.3% (-9.5% to 2.8%; P = .61), respectively.

Conclusions: We were unable to demonstrate a statistically significant increase in macrolide resistance determinants in untreated groups in an azithromycin mass drug administration program. While the result might be consistent with a small spillover effect, this study was not powered to detect such a small difference. Larger studies are warranted to better quantify the potential for spillover effects within these programs.

Trial registration: ClinicalTrials.gov NCT02047981.

Keywords: Niger; antimicrobial resistance; azithromycin; mass drug administration; spillover.

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Conflict of interest statement

Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

Figures

Graphical Abstract
Graphical Abstract
This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/assessment-of-spillover-of-antimicrobial-resistance-to-untreated-children-7-to-12-years-old-after-mass-drug-administration-of-azithromycin-for-child-survival-in-niger-a-secondary-analysis-of-the-mordor-c-d590c4d1-d490-4399-bfba-45e1611c8e80?utm_campaign=tidbitlinkshare&utm_source=ITP
Figure 1.
Figure 1.
Participant flow for the current study.
Figure 2.
Figure 2.
Prevalence of individual resistance markers by antibiotic class and treatment arm among children 7–12 years old at 24 months in the MORDOR morbidity trial in Niger. Gray dots represent individual community prevalence. The x-axis for the macrolide class differs from those for the β-lactam and tetracycline classes. Fluoroquinolones are not shown, as no quantities were detected in either arm.
Figure 3.
Figure 3.
Quantities of individual resistance markers by antibiotic class and treatment arm among children 7–12 years old at 24 months in the MORDOR morbidity trial in Niger.
See this image and copyright information in PMC

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