Francis I Proctor Foundation, University of California, San Francisco, California.
Department of Ophthalmology, University of California, San Francisco, California.
Am J Trop Med Hyg. 2022 Jun 13;107(1):59-64. doi: 10.4269/ajtmh.22-0007. Print 2022 Jul 13.
A broad-spectrum antibiotic, typically amoxicillin, is included in many country guidelines as part of the management of uncomplicated severe acute malnutrition (SAM) in children without overt clinical symptoms of infection. Alternative antibiotics may be beneficial for children with SAM without increasing selection for beta-lactam resistance. We conducted a 1:1 randomized controlled trial of single dose azithromycin versus a 7-day course of amoxicillin for SAM. Children 6-59 months of age with uncomplicated SAM (mid-upper arm circumference < 11.5 cm and/or weight-for-height Z-score < -3) were enrolled in Boromo District, Burkina Faso, from June through October 2020. Rectal swabs were collected at baseline and 8 weeks after treatment and processed using DNA-Seq. We compared the resistome at the class level in children randomized to azithromycin compared with amoxicillin. We found no evidence of a difference in the distribution of genetic antibiotic resistance determinants to any antibiotic class 8 weeks after treatment. There was no difference in genetic macrolide resistance determinants (65% azithromycin, 65% placebo, odds ratio, OR, 1.00, 95% confidence interval, CI, 0.43-2.34) or beta-lactam resistance determinants (82% azithromycin, 83% amoxicillin, OR 0.94, 95% CI, 0.33-2.68) at 8 weeks. Although presence of genetic antibiotic resistance determinants to macrolides and beta-lactams was common, we found no evidence of a difference in the gut resistome 8 weeks after treatment. If there are earlier effects of antibiotics on selection for genetic antibiotic resistance determinants, the resistome may normalize by 8 weeks.
一种广谱抗生素，通常是阿莫西林，被许多国家的指南纳入儿童非复杂性严重急性营养不良（SAM）管理方案，用于治疗没有明显感染临床症状的儿童。替代抗生素可能对没有增加β-内酰胺类药物耐药性选择的 SAM 儿童有益。我们进行了一项 1:1 随机对照试验，比较了单剂量阿奇霉素与 7 天疗程阿莫西林治疗 SAM 的效果。2020 年 6 月至 10 月，在布基纳法索博洛莫区招募了年龄在 6-59 个月、患有非复杂性 SAM（中上臂围<11.5cm 和/或体重身高 Z 评分<-3）的儿童。在基线和治疗 8 周后采集直肠拭子，并使用 DNA-Seq 进行处理。我们比较了随机分配到阿奇霉素组和阿莫西林组的儿童在治疗 8 周后类水平的耐药组。我们没有发现治疗 8 周后任何抗生素类别遗传抗生素耐药决定因素分布的差异。在治疗 8 周后，大环内酯类抗生素耐药决定因素（阿奇霉素 65%，安慰剂 65%，比值比 OR 1.00，95%置信区间 CI 0.43-2.34）或β-内酰胺类抗生素耐药决定因素（阿奇霉素 82%，阿莫西林 83%，OR 0.94，95%CI 0.33-2.68）无差异。尽管大环内酯类和β-内酰胺类抗生素的遗传抗生素耐药决定因素普遍存在，但我们没有发现治疗 8 周后肠道耐药组的差异。如果抗生素对遗传抗生素耐药决定因素的选择有早期影响，那么耐药组可能在 8 周内恢复正常。
