Kong Alex C, So Anthony D
Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Innovation + Design Enabling Access (IDEA) Initiative, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Infect Dis Poverty. 2025 Jul 21;14(1):73. doi: 10.1186/s40249-025-01322-8.
In 2020, the World Health Organization published a guideline on the use of mass drug administration (MDA) of the broad-spectrum antibiotic azithromycin to reduce childhood mortality. As MDA-azithromycin to reduce mortality is considered for expansion to more settings and populations, care must be taken to maximize benefits and reduce risks (e.g., antimicrobial resistance or AMR) of this intervention. Completed and ongoing MDA-azithromycin cluster-randomized clinical trials can provide evidence on the extent to which these benefits and risks accrue and identify practices to monitor these effects and address evidence gaps in future trials.
We examined azithromycin clinical trials registered on ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform from registry inception to December 31, 2023. We included trials for which azithromycin was administered for the prevention or treatment of a disease or condition that was not explicitly diagnosed or necessary for participant inclusion, and for which treatment was randomized by geographic units. We identified evidence, knowledge gaps, and trends and highlights across five domains: (1) targeting of MDA-azithromycin, (2) clinical endpoints, (3) co- and competing interventions, (4) spillover effects, and (5) AMR monitoring.
Of 1589 screened studies, 30 met all inclusion criteria. These trials were conducted in 13 countries, predominantly (26/30) in sub-Saharan Africa. Nearly a third (9/30) of the trials included mortality endpoints, but few (2/9) included cause-specific mortality endpoints. New evidence suggests the benefits of widening the target age group and the persistence of mortality benefits in settings with competing interventions. Published practices to ensure geographic separation of communities in different treatment arms to reduce spillover effects were not customary. We found information on AMR monitoring practices for just over half the trials (16/30). Of these, half (8/16) included both phenotypic and genotypic AMR testing, and more than half collected specimens to assess the nasopharyngeal and gut microbiomes (9/16) and tested for non-macrolide resistance (11/16).
Further long-term MDA-azithromycin studies to determine which additional countries could benefit, interventions to accompany or replace this intervention, and the extent to which AMR spillover occurs may prove valuable as guidelines are revised.
2020年，世界卫生组织发布了一项关于使用广谱抗生素阿奇霉素进行群体药物治疗（MDA）以降低儿童死亡率的指南。由于考虑将使用阿奇霉素进行群体药物治疗以降低死亡率的措施扩大到更多地区和人群，必须谨慎行事，以最大限度地提高这种干预措施的益处并降低风险（例如，抗菌药物耐药性或AMR）。已完成和正在进行的使用阿奇霉素的群体随机临床试验可以提供证据，证明这些益处和风险的产生程度，并确定监测这些影响的方法以及弥补未来试验中的证据空白。
我们审查了在ClinicalTrials.gov和世界卫生组织国际临床试验注册平台上从注册开始至2023年12月31日注册的阿奇霉素临床试验。我们纳入了那些使用阿奇霉素预防或治疗某种疾病或病症的试验，该疾病或病症并非明确诊断或纳入参与者所必需的，并且治疗是按地理单位随机分配的。我们确定了五个领域的证据、知识空白、趋势和要点：（1）阿奇霉素群体药物治疗的目标人群，（2）临床终点，（3）联合和竞争性干预措施，（4）溢出效应，以及（5）抗菌药物耐药性监测。
在1589项筛选的研究中，30项符合所有纳入标准。这些试验在13个国家进行，主要在撒哈拉以南非洲（26/30）。近三分之一（9/30）的试验纳入了死亡率终点，但很少有试验（2/9）纳入特定病因死亡率终点。新证据表明扩大目标年龄组的益处以及在存在竞争性干预措施的环境中死亡率益处的持续性。已发表的确保不同治疗组中的社区地理隔离以减少溢出效应的做法并不常见。我们仅在略多于一半的试验（16/30）中发现了关于抗菌药物耐药性监测做法的信息。其中，一半（8/16）包括表型和基因型抗菌药物耐药性检测，超过一半收集标本以评估鼻咽和肠道微生物群（9/16）并检测非大环内酯类耐药性（11/16）。
随着指南的修订，进一步开展长期的使用阿奇霉素的群体药物治疗研究，以确定哪些其他国家可能受益、伴随或替代该干预措施的干预措施以及抗菌药物耐药性溢出发生的程度，可能会很有价值。
