Rolfe Robert J, Shaikh Hassaan, Tillekeratne L Gayani
Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
Duke Global Health Institute, Duke University, Durham, NC, USA.
Infect Dis Poverty. 2022 Jun 30;11(1):77. doi: 10.1186/s40249-022-00998-6.
Mass drug administration (MDA) is a strategy to improve health at the population level through widespread delivery of medicine in a community. We surveyed the literature to summarize the benefits and potential risks associated with MDA of antibacterials, focusing predominantly on azithromycin as it has the greatest evidence base.
High-quality evidence from randomized controlled trials (RCTs) indicate that MDA-azithromycin is effective in reducing the prevalence of infection due to yaws and trachoma. In addition, RCTs suggest that MDA-azithromycin reduces under-five mortality in certain low-resource settings that have high childhood mortality rates at baseline. This reduction in mortality appears to be sustained over time with twice-yearly MDA-azithromycin, with the greatest effect observed in children < 1 year of age. In addition, observational data suggest that infections such as skin and soft tissue infections, rheumatic heart disease, acute respiratory illness, diarrheal illness, and malaria may all be treated by azithromycin and thus incidentally impacted by MDA-azithromycin. However, the mechanism by which MDA-azithromycin reduces childhood mortality remains unclear. Verbal autopsies performed in MDA-azithromycin childhood mortality studies have produced conflicting data and are underpowered to answer this question. In addition to benefits, there are several important risks associated with MDA-azithromycin. Direct adverse effects potentially resulting from MDA-azithromycin include gastrointestinal side effects, idiopathic hypertrophic pyloric stenosis, cardiovascular side effects, and increase in chronic diseases such as asthma and obesity. Antibacterial resistance is also a risk associated with MDA-azithromycin and has been reported for both gram-positive and enteric organisms. Further, there is the risk for cross-resistance with other antibacterial agents, especially clindamycin.
Evidence shows that MDA-azithromycin programs may be beneficial for reducing trachoma, yaws, and mortality in children < 5 years of age in certain under-resourced settings. However, there are significant potential risks that need to be considered when deciding how, when, and where to implement these programs. Robust systems to monitor benefits as well as adverse effects and antibacterial resistance are warranted in communities where MDA-azithromycin programs are implemented.
群体药物给药（MDA）是一种通过在社区广泛分发药物来改善人群健康状况的策略。我们对文献进行了调研，以总结与抗菌药物群体药物给药相关的益处和潜在风险，主要聚焦于阿奇霉素，因为其有最充分的证据基础。
随机对照试验（RCT）的高质量证据表明，群体药物给药阿奇霉素在降低雅司病和沙眼感染患病率方面是有效的。此外，随机对照试验表明，在某些基线儿童死亡率较高的资源匮乏地区，群体药物给药阿奇霉素可降低五岁以下儿童死亡率。随着每年两次的群体药物给药阿奇霉素，这种死亡率的降低似乎会随着时间持续存在，在1岁以下儿童中观察到的效果最为显著。此外，观察性数据表明，诸如皮肤和软组织感染、风湿性心脏病、急性呼吸道疾病、腹泻病和疟疾等感染都可能用阿奇霉素治疗，因此群体药物给药阿奇霉素可能会对其产生附带影响。然而，群体药物给药阿奇霉素降低儿童死亡率的机制仍不清楚。在群体药物给药阿奇霉素儿童死亡率研究中进行的死因推断得出了相互矛盾的数据，且不足以回答这个问题。除了益处之外，群体药物给药阿奇霉素还存在一些重要风险。群体药物给药阿奇霉素可能导致的直接不良反应包括胃肠道副作用、特发性肥厚性幽门狭窄、心血管副作用以及哮喘和肥胖等慢性疾病的增加。抗菌药物耐药性也是群体药物给药阿奇霉素相关的风险，革兰氏阳性菌和肠道菌都有相关报道。此外，还存在与其他抗菌药物交叉耐药的风险，尤其是克林霉素。
证据表明，群体药物给药阿奇霉素项目可能有利于在某些资源匮乏地区降低沙眼、雅司病以及五岁以下儿童的死亡率。然而，在决定如何、何时以及何地实施这些项目时，需要考虑重大的潜在风险。在实施群体药物给药阿奇霉素项目的社区，有必要建立强有力的系统来监测益处、不良反应和抗菌药物耐药性。
