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选择研究中的一个感兴趣的主题。研究表明，即使在远低于最低抑菌浓度(MIC)的浓度下，与没有抗药性的细菌相比，具有抗药性的细菌也可以获得选择性优势。现有的研究集中在土壤/沉积物中的环境残留的体外实验和研究上，但还没有集中在特定治疗方案对人群中MSC的影响上。目前的奶牛场做法在牛身上使用了许多抗菌剂，这些抗菌剂最终可能会进入牛奶中(各种干牛疗法、全身疗法)。由于AMR残留，处理后的牛乳在超过最低提取时间之前不能用于商业用途，但可用于小牛饲料和初乳转移，具体取决于具体的牧场做法。不同的乳房内干奶牛制剂在配方上可能不同，在控制革兰氏阴性和革兰氏阳性细菌方面可能存在偏差。例如，狮子座红干牛有显着的革兰氏阴性覆盖率，而奥本宁额外DC没有具体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。青霉素类药物的使用仍有可能推动对超广谱β-内酰胺酶的耐药性选择，并可能在革兰氏阴性菌之间传播。田野。虽然氨基糖苷类药物经常用于治疗耐多药革兰氏阴性菌感染，但在潜在的人畜共患病人群中，可能增加氨基糖苷类药物抗药性的选择给更广泛的卫生界带来了潜在的问题。来自EVAL农场项目的初步数据将表明，抗生素的使用会导致特定耐药性的爆发。目标：(I)我们将调查具有不同管理实践的奶牛群，以确定使用这些产品进行选择是否存在潜在的风险，因为这些产品会在奶牛的肠道中产生抵抗力，并在它们生长过程中保持下去。(Ii)该项目将评估各种抗菌疗法对牛的影响，这些疗法可能导致奶牛环境中随后的低浓度抗菌剂。(Iii)此外，我们还研究了这些耐药性的携带机制，以及它们与其他抗菌药共同选择和转移到相关细菌属的可能性。结果：我们的目标是确定有选择性压力的农场实践。这样，在特定产品的干牛治疗期间使用牛奶的建议可以被视为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.