Sievers Theresa, Blumenberg Julia A, Hölzel Christina S
Institute for Animal Breeding & Husbandry, Faculty for Agricultural & Nutritional Sciences, Kiel University, 24098 Kiel, Germany.
Institute for Animal Breeding & Husbandry, Faculty for Agricultural & Nutritional Sciences, Kiel University, 24098 Kiel, Germany.
J Dairy Sci. 2025 May;108(5):4508-4543. doi: 10.3168/jds.2024-25528. Epub 2024 Dec 6.
The occurrence of antibiotic resistance genes (ARG) in milk is eagerly discussed as a public health risk, and frequently investigated. Here, we perform a systematic review on the abundance of antimicrobial resistance genes in milk from primary production over a 10-year period. We aim to provide a comprehensive dataset on known and emerging antimicrobial resistance genes in major mastitis pathogens, occurring worldwide in milk at primary production, and to critically discuss the relevance and constraints of these findings. We searched PubMed for peer-reviewed studies published between 2012 and 2022 that fit fixed combinations of key words and did not meet exclusion criteria such as "mixed with other sources." For synthesis, data on occurrence was extracted from studies and supplements. To address plausibility issues, we performed an National Center of Biotechnology Information Basic Local Alignment Search Tool (BLAST) search. Our search revealed 2,222 publications in total. Of them, 500 studies were eligible for full-text reads and 306 publications were included in data compilation. An overwhelming majority of studies dealt with mecA in Staphylococcus aureus, followed by extended-spectrum β-lactamase-encoding genes such as blaCTXM in Escherichia coli, while other mastitis pathogens, such as Streptococcus spp., were scarcely investigated. In most cases, <5% of milk samples were positive for major pathogens bearing the antimicrobial resistance gene of interest. However, huge study-to-study differences were found between regions, but also on a national level. For instance, the estimate prevalence of Escherichia coli-borne blaCTXM in mastitis milk samples ranged from 0.0% to 55%, with a median value of 7.3%, but in healthy individuals and bulk milk, the prevalence ranged from 0.0% to 20.0%, with a median value of 0.8%. Several studies reported antimicrobial resistance genes for the very first time in a species, but did not stand up to scrutiny. As an example, frequent detection of blaTEM-genes in streptococci is most likely attributed to contamination of molecular reagents, as reported elsewhere. Despite the large amount of data, there is a need for more quality control, more representative sampling of milk, more quantitative research, and deeper insights into bacterial genomics, to identify relevant or emerging antimicrobial resistance genes in milk. Considering a low percentage of contaminated milk samples, unknown ARG concentrations, and an unproven role in human disease, the risk attributed to ARG in milk seems to be exaggerated by far. However, the risk of ARG selection on farm, resulting in low treatment success in cattle, is a real one and should be met by prudent use of antibiotics.
牛奶中抗生素抗性基因（ARG）的出现作为一种公共卫生风险备受热议，并经常被研究。在此，我们对10年间初级生产牛奶中抗菌药物抗性基因的丰度进行了系统综述。我们旨在提供一个关于主要乳腺炎病原体中已知和新出现的抗菌药物抗性基因的综合数据集，这些病原体在全球初级生产的牛奶中均有出现，并对这些发现的相关性和局限性进行批判性讨论。我们在PubMed上搜索了2012年至2022年间发表的符合关键词固定组合且未满足“与其他来源混合”等排除标准的同行评审研究。为了进行综合分析，从研究及其补充材料中提取了关于出现情况的数据。为了解决合理性问题，我们进行了美国国立生物技术信息中心基本局部比对搜索工具（BLAST）搜索。我们的搜索总共发现了2222篇出版物。其中，500项研究符合全文阅读条件，306篇出版物被纳入数据汇编。绝大多数研究涉及金黄色葡萄球菌中的mecA基因，其次是大肠杆菌中编码超广谱β-内酰胺酶的基因，如blaCTXM，而其他乳腺炎病原体，如链球菌属，很少被研究。在大多数情况下，<5%的牛奶样本对携带感兴趣的抗菌药物抗性基因的主要病原体呈阳性。然而，在不同地区之间以及在国家层面上都发现了研究之间存在巨大差异。例如，乳腺炎牛奶样本中大肠杆菌携带的blaCTXM的估计患病率在0.0%至55%之间，中位数为7.3%，但在健康个体和散装牛奶中，患病率在0.0%至20.0%之间，中位数为0.8%。一些研究首次报道了某一物种中的抗菌药物抗性基因，但经不起推敲。例如，如其他地方所报道的，在链球菌中频繁检测到blaTEM基因很可能归因于分子试剂的污染。尽管有大量数据，但仍需要更多的质量控制、更具代表性的牛奶采样、更多的定量研究以及对细菌基因组学的更深入了解，以识别牛奶中相关的或新出现的抗菌药物抗性基因。考虑到受污染牛奶样本的比例较低、ARG浓度未知以及其在人类疾病中的作用未经证实，牛奶中ARG所带来的风险似乎被大大夸大了。然而，农场中ARG选择导致牛治疗成功率低的风险是真实存在的，应该通过谨慎使用抗生素来应对。
