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 aims to understand the risk of spillover of antibiotic resistance to non-target groups in these programs. Methods Data was used from a cluster-randomized trial comparing the effect of biannual azithromycin and placebo distribution to children 1-59 months on child mortality. 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 timepoint adjusting for baseline prevalence. Results 1,103 children 7-12 years old in 30 communities were included in the analysis (15 azithromycin, 15 placebo). Adjusted mean differences in prevalence of resistance determinants for macrolides, beta-lactams and tetracyclines were 3.4% (95% CI -4.1% to 10.8%, P-value 0.37), -1.2% (95% CI -7.9% to 5.5%, P-value 0.72), and -3.3% (95% CI -9.5% to 2.8%, P-value 0.61), 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 understand the potential for spillover effects within these programs.

中文翻译：

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尼日尔大规模阿奇霉素给药后对 7 至 12 岁未经治疗儿童的抗菌药物耐药性溢出评估，以提高儿童生存率：MORDOR 整群随机试验的二次分析


背景 抗生素耐药性的风险因一个治疗人群对另一人群潜在的溢出效应而变得复杂。阿奇霉素大规模药物管理计划报告称，目标群体的治疗组中抗生素耐药率较高。本研究旨在了解抗生素耐药性向这些计划中的非目标群体蔓延的风险。方法 使用整群随机试验的数据，该试验比较了每两年一次向 1-59 个月的儿童分发阿奇霉素和安慰剂对儿童死亡率的影响。对未经治疗的 7-12 岁儿童的鼻咽样本进行了大环内酯类耐药性（主要结果）和其他抗生素类别耐药性（次要结果）的遗传决定因素的检测。使用线性回归来比较在调整基线患病率的 24 个月时间点各组的社区水平患病率平均差异。结果 30 个社区的 1,103 名 7-12 岁儿童被纳入分析（15 名阿奇霉素，15 名安慰剂）。大环内酯类、β-内酰胺类和四环素类耐药决定因素患病率的调整后平均差异分别为 3.4%（95% CI -4.1% 至 10.8%，P 值 0.37）、-1.2%（95% CI -7.9% 至 5.5%， P 值 0.72）和 -3.3%（95% CI -9.5% 至 2.8%，P 值 0.61）。结论 我们无法证明在阿奇霉素大规模给药计划中未经治疗的组中大环内酯类耐药决定因素有统计学上的显着增加。虽然结果可能与小的溢出效应一致，但这项研究无法检测到如此小的差异。有必要进行更大规模的研究，以更好地了解这些计划中潜在的溢出效应。