Francis I. Proctor Foundation, University of California, San Francisco, California, USA.
Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA.
Clin Infect Dis. 2024 Nov 22;79(5):1136-1143. doi: 10.1093/cid/ciae267.
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.
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.
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.
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.
抗生素耐药性的风险因一个治疗人群的溢出效应对另一个治疗人群的潜在影响而变得复杂。阿奇霉素大规模药物管理方案报告称，目标人群治疗组中的抗生素耐药率更高。本研究旨在了解这些方案中非目标人群抗生素耐药性溢出的风险。
本研究使用了一项比较每 6 个月一次给予阿奇霉素和安慰剂对 1-59 个月大儿童死亡率影响的整群随机试验的数据。对未接受治疗的 7-12 岁儿童的鼻咽样本进行了大环内酯类药物耐药的遗传决定因素（主要结局）和对其他抗生素类别的耐药性（次要结局）检测。线性回归用于比较 24 个月时手臂组间社区水平的平均差异，调整了基线流行率。
共纳入 30 个社区的 1103 名 7-12 岁儿童（15 名阿奇霉素，15 名安慰剂）进行分析。大环内酯类药物、β-内酰胺类药物和四环素耐药决定因素的调整后平均差异分别为 3.4%（95%置信区间，-4.1%至 10.8%；P =.37）、-1.2%（-7.9%至 5.5%；P =.72）和-3.3%（-9.5%至 2.8%；P =.61）。
我们无法证明在阿奇霉素大规模药物管理方案中，未接受治疗组大环内酯类药物耐药决定因素有统计学上显著增加。虽然这一结果可能与小的溢出效应一致，但本研究没有足够的能力来检测到如此小的差异。需要更大的研究来更好地量化这些方案中溢出效应的潜力。
