Andersen V D, Aarestrup F M, Munk P, Jensen M S, de Knegt L V, Bortolaia V, Knudsen B E, Lukjancenko O, Birkegård A C, Vigre H
The National Food Institute, Technical University of Denmark, Lyngby, Denmark.
The National Food Institute, Technical University of Denmark, Lyngby, Denmark.
Prev Vet Med. 2020 Jan;174:104853. doi: 10.1016/j.prevetmed.2019.104853. Epub 2019 Nov 19.
It is accepted that usage of antimicrobials (AMs) in food animals causes the emergence and spread of antimicrobial resistance (AMR) in this sector, while also contributing to the burden of AMR in humans. Curbing the increasing occurrence of AMR in food animals requires in-depth knowledge of the quantitative relationship between antimicrobial usage (AMU) and AMR to achieve desired resistance reductions from interventions targeting AMU. In the observational study, the relationships between lifetime AMU in 83 finisher batches from Danish farms and the AMR gene abundances of seven antimicrobial classes in their gut microbiomes were quantified using multi-variable linear regression models. These relationships and the national lifetime AMU in pigs were included in the predictive modelling that allowed for testing of scenarios with changed lifetime AMU for finishers produced in Denmark in 2014. A total of 50 farms from the observational study were included in validating the observational study and the predictive modelling. The results from the observational study showed that the relationship was linear, and that the parenteral usage of AMs had a high effect on specific AM-classes of resistance, whereas the peroral usage had a lower but broader effect on several classes. Three different scenarios of changed lifetime AMU were simulated in the predictive modelling. When all tetracycline usage ceased, the predicted interval reductions of aminoglycoside, lincosamide and tetracycline resistance were 4-42 %, 0-8 % and 9-18 %, respectively. When the peroral tetracycline usage of the 10 % highest users was replaced with peroral macrolide usage, the tetracycline resistance fell by 1-2 % and the macrolide and MLSb resistance increased by 5-8 %. When all extended-spectrum penicillin usage was replaced with parenteral lincosamide usage, the beta-lactam resistance fell by 2-7 %, but the lincosamide usage and resistance increased by 194 % and 10-45 %, respectively. The external validation provided results within the 95 % CI of the predictive modelling outcome at national level, while the external validation at farm level was less accurate. In conclusion, interventions targeting AMU will reduce AMR abundance, though differently depending on the targeted AM-class and provided the reduction of one AM-class usage is not replaced with usage of another AM-class. Predicting several classes of AMR gene abundance simultaneously will support stakeholders when deciding on interventions targeting AMU in the finisher production to avoid adverse and unforeseen effects on the AMR abundance. This study provides a sound predictive modelling framework for further development, including the dynamics of AMU on AMR in finishers at national level.
人们普遍认为，食用动物中使用抗菌药物会导致该领域抗菌药物耐药性（AMR）的出现和传播，同时也会加重人类的AMR负担。控制食用动物中AMR发生率的不断上升，需要深入了解抗菌药物使用量（AMU）与AMR之间的定量关系，以便通过针对AMU的干预措施实现预期的耐药性降低。在这项观察性研究中，使用多变量线性回归模型量化了来自丹麦农场的83个育肥批次猪一生的AMU与其肠道微生物群中七种抗菌药物类别的AMR基因丰度之间的关系。这些关系以及丹麦猪一生的全国AMU被纳入预测模型，该模型可用于测试2014年丹麦生产的育肥猪一生AMU变化的情景。观察性研究中的50个农场被纳入验证观察性研究和预测模型。观察性研究结果表明，这种关系是线性的，并且抗菌药物的注射使用对特定抗菌药物类别的耐药性有很大影响，而口服使用对几个类别有较低但更广泛的影响。在预测模型中模拟了三种不同的一生AMU变化情景。当所有四环素使用停止时，预测的氨基糖苷类、林可酰胺类和四环素类耐药性的区间降低分别为4 - 42%、0 - 8%和9 - 18%。当10%最高用量用户的口服四环素使用被口服大环内酯类使用取代时，四环素耐药性下降1 - 2%，大环内酯类和MLSb耐药性增加5 - 8%。当所有广谱青霉素使用被注射林可酰胺类使用取代时，β-内酰胺类耐药性下降2 - 7%，但林可酰胺类使用和耐药性分别增加194%和10 - 45%。外部验证在国家层面提供了预测模型结果95%置信区间内的结果，而农场层面的外部验证不太准确。总之，针对AMU的干预措施将降低AMR丰度，尽管根据目标抗菌药物类别不同而有所不同，并且前提是一种抗菌药物类别的使用减少不会被另一种抗菌药物类别的使用所取代。在决定针对育肥猪生产中AMU的干预措施时，同时预测几类AMR基因丰度将为利益相关者提供支持，以避免对AMR丰度产生不利和不可预见的影响。本研究为进一步发展提供了一个可靠的预测模型框架，包括国家层面育肥猪中AMU对AMR的动态影响。
