Drivers and vectors for AMR selection and transmission on dairy farms.

工作背景和背景：最小选择浓度（MSC）已成为环境AMR选择研究中的一个热门话题。研究表明，即使在远低于最低抑菌浓度（MIC）的浓度下，与没有耐药性的细菌相比，具有耐药性的细菌也可以获得选择性优势。现有的研究主要集中在体外实验和土壤/沉积物中环境残留物的研究，但没有关注特定治疗方案对MSC在人群中的影响。目前奶牛场的做法是在牛身上使用许多抗菌剂，这些抗菌剂可能最终进入牛奶中（各种干奶牛疗法，全身治疗）。由于AMR残留，治疗后牛的乳汁在超过最低停药时间之前不能用于商业用途，但根据具体的农场实践，确实可用于小牛饲料和初乳转移。不同的干乳期奶牛乳房内制剂的配方可能不同，并且在控制革兰氏阴性菌和革兰氏阳性菌的覆盖率方面可能存在偏差。例如，Leo Red Dry Cow具有显著的革兰氏阴性覆盖率，而Orbenin Extra DC没有特定的革兰氏阴性覆盖率。在与它们相互作用的细菌群落中有不同的选择潜力。青霉素的使用仍然有可能推动对ESBLs的抗性的选择，并且可以在革兰氏阴性菌之间循环。外地虽然氨基糖苷类药物经常用于治疗MDR革兰氏阴性菌感染，但在潜在的人畜共患病储库中增加对氨基糖苷类药物耐药性的选择对更广泛的健康社区构成了潜在的问题。来自EVAL农场项目的可靠数据表明，抗生素的使用会导致特定耐药性的大量产生。目的：（i）我们会调查采用不同管理方法的奶牛群，以确定是否有潜在的选择风险，即使用产品会使奶牛的内脏产生抵抗力，而这种抵抗力可随奶牛的生长而维持。(ii)该项目将评估不同抗菌治疗对牛的影响，这些治疗可能导致乳制品环境中随后出现低水平的抗菌剂浓度。(iii)此外，我们还研究了这些耐药性的携带机制及其与其他抗菌剂共选择和转移到相关细菌属的潜力。结果：我们的目标是确定具有选择压力的农场实践。因此，关于在干奶牛治疗期间使用特定产品的牛奶的建议可被视为AMR管理计划的一部分。

Background and context of the work: Minimum selective concentrations (MSC) have become a topic of interest in the investigation of environmental AMR selection. Studies indicate that even at concentrations well below the minimum inhibitory concentration (MIC) a selective advantage can be gained by bacteria with existing resistances compared to those without. Existing studies have focused on in vitro experiments and study of environmental residues in soils/sediments but none focus on the impact of MSC in populations caused by specific therapeutic regimens. Current dairy farm practices use a number of antimicrobials on cattle which can end up in the milk (Varied dry cow therapies, systemic treatments). Milks from cattle post treatment cannot be used commercially due to AMR residues until past the minimum withdrawal time but do get used for calves for feed and for colostrum transfer depending on specific farm practices. Different intramammary dry cow preparations can differ in their formulations and can be biased in their coverage for control of Gram negative and Gram positive bacteria. For example Leo Red Dry Cow has significant Gram negative coverage while Orbenin Extra DC has no specific Gram negative coverage. There are different potentials for selection within the bacterial communities with which they interact. The use of penicillins still have the potential to drive selection for resistances to ESBLs and that could circulate between Gram negative bacteria. the field. While aminoglycosides are often used for treatment of MDR Gram negative infection so selections which can increase resistance to aminoglycosides in potentially zoonotic reservoirs pose a potential problem for the wider health community. Prelim airy Data form the EVAL farms project would indicate that antibiotic use can lead to blooms of specific resistances. Aims: (i) We will investigate dairy herds which have different management practices to determine if there is potential risk of selection using the products in developing resistance in the guts of claves that can be maintained as they grow. (ii) This project will assess the impact of varied antimicrobial therapies on cattle that can lead subsequent low level concentrations of antimicrobial in the dairy environment. (iii) In addition we investigate the mechanism of carriage of these resistances and their potential for co-selection of other antimicrobials and transfer to related bacterial genera. Outcomes: We aim to identify on-farm practices, which have selective pressure. Such that recommendations on use of milk during dry cow therapy with specific products could be considered as part of an AMR stewardship program.