美国加州大学旧金山分校Thomas M. Lietman团队研究了阿奇霉素降低非洲儿童死亡率的效果。这一研究成果于2024年8月22日发表在《新英格兰医学杂志》上。

每年两次向儿童大规模分发阿奇霉素是降低撒哈拉以南非洲儿童死亡率的一种有前景的干预措施。世界卫生组织建议限制向1至11个月大的婴儿分发，以减轻抗菌素耐药性，尽管这种更有限的治疗方法尚未经过检验。

研究组将尼日尔的农村社区随机分配，分别对1至59个月大的儿童每年分配两次阿奇霉素（儿童阿奇霉素组），1至11个月大婴儿每年分配两次阿奇霉素和12至59个月大儿童每年分配两次安慰剂（婴儿阿奇霉素组），或1至59月大儿童每年两次分配安慰剂。在2年的时间里，双盲小组任务的人口普查工作人员每年监测两次死亡率。研究组评估了三组主要社区一级死亡率结局（每1000人年的死亡人数），每种结局都检查了不同的年龄组和成对组比较。

共有1273个社区被随机分配到儿童阿奇霉素组（1229个社区被纳入分析），773个社区被分配到婴儿阿奇霉素组（751个社区），954个社区被分配到安慰剂组（929个社区）。在382586名儿童中，记录了419440人年和5503人死亡。阿奇霉素组1至59个月大的儿童死亡率（每1000人年11.9例死亡；95%置信区间[CI]，11.3至12.6）低于安慰剂组（每1000人年13.9例死亡；95%CI，13.0至14.8）（阿奇霉素组死亡率降低14%；95%CI7至22；P<0.001）。婴儿阿奇霉素组1至11个月婴儿的死亡率（每1000人年22.3例死亡；95%CI，20.0至24.7）与安慰剂组（每1000个人年23.9例死亡；95%CI，21.6至26.2）相比没有显著降低（阿奇霉素组的死亡率降低了6%；95%CI为-8至19）。共报告了5起严重不良事件：安慰剂组3起，婴儿阿奇霉素组1起，儿童阿奇霉素组1例。

研究结果表明，阿奇霉素在1至59个月大的儿童中的分配显著降低了死亡率，并且比治疗1至11个月大婴儿更有效。但必须监测抗菌素耐药性。

附：英文原文

Title: Azithromycin to Reduce Mortality — An Adaptive Cluster-Randomized Trial

Author: Kieran S. O’Brien, Ahmed M. Arzika, Abdou Amza, Ramatou Maliki, Bawa Aichatou, Ismael Mamane Bello, Diallo Beidi, Nasser Galo, Naser Harouna, Alio M. Karamba, Sani Mahamadou, Moustapha Abarchi, Almou Ibrahim, Elodie Lebas, Brittany Peterson, Zijun Liu, Victoria Le, Emily Colby, Thuy Doan, Jeremy D. Keenan, Catherine E. Oldenburg, Travis C. Porco, Benjamin F. Arnold, Thomas M. Lietman

Issue&Volume: 2024-08-22

Abstract:

BACKGROUND

Twice-yearly mass distribution of azithromycin to children is a promising intervention to reduce childhood mortality in sub-Saharan Africa. The World Health Organization recommended restricting distribution to infants 1 to 11 months of age to mitigate antimicrobial resistance, although this more limited treatment had not yet been tested.

METHODS

We randomly assigned rural communities in Niger to four twice-yearly distributions of azithromycin for children 1 to 59 months of age (child azithromycin group), four twice-yearly distributions of azithromycin for infants 1 to 11 months of age and placebo for children 12 to 59 months of age (infant azithromycin group), or placebo for children 1 to 59 months of age. Census workers who were not aware of the group assignments monitored mortality twice yearly over the course of 2 years. We assessed three primary community-level mortality outcomes (deaths per 1000 person-years), each examining a different age group and pairwise group comparison.

RESULTS

A total of 1273 communities were randomly assigned to the child azithromycin group (1229 were included in the analysis), 773 to the infant azithromycin group (751 included in the analysis), and 954 to the placebo group (929 included in the analysis). Among 382,586 children, 419,440 person-years and 5503 deaths were recorded. Lower mortality among children 1 to 59 months of age was observed in the child azithromycin group (11.9 deaths per 1000 person-years; 95% confidence interval [CI], 11.3 to 12.6) than in the placebo group (13.9 deaths per 1000 person-years; 95% CI, 13.0 to 14.8) (representing 14% lower mortality with azithromycin; 95% CI, 7 to 22; P<0.001). Mortality among infants 1 to 11 months of age was not significantly lower in the infant azithromycin group (22.3 deaths per 1000 person-years; 95% CI, 20.0 to 24.7) than in the placebo group (23.9 deaths per 1000 person-years; 95% CI, 21.6 to 26.2) (representing 6% lower mortality with azithromycin; 95% CI, 8 to 19). Five serious adverse events were reported: three in the placebo group, one in the infant azithromycin group, and one in the child azithromycin group.

CONCLUSIONS

Azithromycin distributions to children 1 to 59 months of age significantly reduced mortality and was more effective than treatment of infants 1 to 11 months of age. Antimicrobial resistance must be monitored.

DOI: NJ202408223910809

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2312093