Emes Eve, Belay Dagim, Knight Gwenan M
Centre for the Mathematical Modelling of Infectious Diseases (CMMID), London School of Hygiene and Tropical Medicine, London, UK.
Department of Food and Resource Economics, University of Copenhagen, Copenhagen, Denmark.
One Health. 2024 Jul 22;19:100856. doi: 10.1016/j.onehlt.2024.100856. eCollection 2024 Dec.
Antibiotic use (ABU) in animals is postulated to be a major contributor to selection of antibiotic resistance (ABR) which subsequently causes infections in human populations. However, there are few quantifications of the size of this association. Denmark, as a country with high levels of pig production and strong ABR surveillance data, is an ideal case study for exploring this association. This study compiles a dataset on ABU across several animal species and antibiotic classes, and data on the rate of antibiotic resistance (ABR) in humans across key pathogens, in Denmark over time (2010-2020). Panel data regressions (fixed effects, random effects, first difference and pooled ordinary least squares) were used to test the association between the level of ABR in human isolates and the level of ABU in animals. A positive relationship was identified between ABR in humans and ABU in cattle, with some evidence of a positive relationship for poultry and companion animals, and a negative relationship for fish, although the latter is likely driven by confounding factors. When lagging ABU by one year, the effect of ABU in cattle and companion animals remained similar, the effect of ABU in poultry fell in size, and ABU in fish was no longer significant, perhaps due to differences in life cycle length among animal species. Additional covariates were explored, including pet populations, agricultural production and GDP per capita (at purchasing power parity), but these results were limited by the statistical power of the dataset. Under all models, animal ABU determined only a minority of the change in human ABR levels in this context with adjusted R ranging from 0.19 to 0.44. This paper supports the role of animal ABU in determining human ABR levels but suggests that, despite comprising a large portion of systemwide ABU, it only explains a minority of the variation. This is likely driven in part by data limitations, and could also be due to a persistence of ABR once resistance has emerged, suggesting a significant role for socioeconomic and transmission factors in bringing ABR down to desirable levels.
动物使用抗生素（ABU）被认为是导致抗生素耐药性（ABR）产生的主要因素，而抗生素耐药性随后会引发人类感染。然而，对于这种关联的规模，量化研究却很少。丹麦作为一个生猪产量高且拥有强大抗生素耐药性监测数据的国家，是探索这种关联的理想案例研究对象。本研究汇编了丹麦不同动物物种和抗生素类别在一段时间（2010 - 2020年）内的抗生素使用数据集，以及人类关键病原体的抗生素耐药率（ABR）数据。使用面板数据回归（固定效应、随机效应、一阶差分和混合普通最小二乘法）来检验人类分离株中的抗生素耐药水平与动物抗生素使用水平之间的关联。研究发现人类的抗生素耐药性与牛的抗生素使用之间存在正相关关系，有证据表明家禽和伴侣动物也存在正相关关系，而鱼类存在负相关关系，不过后者可能是由混杂因素导致的。当将抗生素使用滞后一年时，牛和伴侣动物的抗生素使用影响仍然相似，家禽的抗生素使用影响程度减小，而鱼类的抗生素使用不再显著，这可能是由于动物物种生命周期长度的差异所致。研究还探索了其他协变量，包括宠物数量、农业生产和人均国内生产总值（按购买力平价计算），但这些结果受到数据集统计能力的限制。在所有模型下，在这种情况下，动物抗生素使用仅决定了人类抗生素耐药水平变化的一小部分，调整后的R值范围为0.19至0.44。本文支持动物抗生素使用在决定人类抗生素耐药水平方面的作用，但表明尽管动物抗生素使用占整个系统抗生素使用的很大一部分，但它仅解释了变异的一小部分。这可能部分是由数据限制导致的，也可能是由于耐药性一旦出现就会持续存在，这表明社会经济和传播因素在将抗生素耐药性降低到理想水平方面具有重要作用。
