Division of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Department of Population Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Microbiol Spectr. 2024 Oct 3;12(10):e0097024. doi: 10.1128/spectrum.00970-24. Epub 2024 Sep 13.
Antimicrobial resistance (AMR) is an emerging worldwide problem and a health threat for humans and animals. Antimicrobial usage in human and animal medicine or in agriculture results in selection for AMR. The selective concentration of antimicrobial compounds can be lower than the minimum inhibitory concentration and differs between environments, which can be a reason for bacterial resistance. Therefore, knowledge of the minimal selective concentration (MSC), under natural conditions, is essential to understand the selective window of bacteria when exposed to residual antimicrobials. In this study, we estimated the MSCs of three antimicrobials, amoxicillin, doxycycline, and enrofloxacin in a complex microbial community by conducting fermentation assays with cecal material derived from broilers. We examined the phenotypic resistance of , resistome, and microbiome after 6 and 30 hours of fermenting in the presence of the antimicrobials of interest. The concentrations were estimated to be 10-100 times lower than the epidemiological cut-off values in for the respective antimicrobials as determined by EUCAST, resulting in an MSC between 0.08 and 0.8 mg/L for amoxicillin, 0.4 and 4 mg/L for doxycycline, and 0.0125 and 0.125 mg/L for enrofloxacin. Additionally, resistome analysis provided an MSC for doxycycline between 0.4 and 4 mg/L, but amoxicillin and enrofloxacin exposure did not induce a significant difference. Our findings indicate at which concentrations there is still selection for antimicrobial-resistant bacteria. This knowledge can be used to manage the risk of the emergence of antimicrobial-resistant bacteria.IMPORTANCEAntimicrobial resistance possibly affects human and animal health, as well as economic prosperity in the future. The rise of antimicrobial-resistant bacteria is a consequence of using antimicrobial compounds in humans and animals selecting for antimicrobial-resistant bacteria. Concentrations reached during treatment are known to be selective for resistant bacteria. However, at which concentrations residues are still selective is important, especially for antimicrobial compounds that remain in the environment at low concentrations. The data in this paper might inform decisions regarding guidelines and regulations for the use of specific antimicrobials. In this study, we are providing these minimal selective concentrations for amoxicillin, doxycycline, and enrofloxacin in complex environments.
抗微生物药物耐药性（AMR）是一个全球范围内正在出现的问题，也是人类和动物的健康威胁。在人类和动物医学或农业中使用抗微生物药物会导致 AMR 的选择。抗微生物化合物的选择性浓度可能低于最低抑菌浓度，并且在环境之间存在差异，这可能是细菌产生耐药性的一个原因。因此，了解自然条件下的最小选择浓度（MSC）对于理解暴露于残留抗微生物药物的细菌的选择窗口至关重要。在这项研究中，我们通过用来自肉鸡的盲肠物质进行发酵试验，估计了三种抗生素（阿莫西林、多西环素和恩诺沙星）在复杂微生物群落中的 MSC。我们在存在感兴趣的抗生素的情况下，分别在 6 小时和 30 小时后检查了表型耐药性、抗性组和微生物组。根据欧盟药敏试验委员会（EUCAST）的规定，所确定的浓度分别比各自抗生素的流行病学切点值低 10-100 倍，结果得出阿莫西林的 MSC 为 0.08-0.8 mg/L，多西环素为 0.4-4 mg/L，恩诺沙星为 0.0125-0.125 mg/L。此外，抗性组分析为多西环素提供了 0.4-4 mg/L 的 MSC，但阿莫西林和恩诺沙星暴露并没有引起显著差异。我们的研究结果表明，在何种浓度下仍存在对抗微生物药物耐药菌的选择。这些知识可用于管理抗微生物药物耐药菌出现的风险。
抗微生物药物耐药性可能会影响人类和动物的健康，以及未来的经济繁荣。抗微生物药物耐药菌的出现是由于在人类和动物中使用抗微生物化合物而导致的选择抗微生物药物耐药菌的结果。治疗过程中达到的浓度已知对抗菌药物耐药菌具有选择性。然而，残留物质仍然具有选择性的浓度很重要，特别是对于在低浓度下仍存在于环境中的抗微生物化合物。本文的数据可能为特定抗微生物药物使用的指南和法规的决策提供信息。在这项研究中，我们在复杂环境中为阿莫西林、多西环素和恩诺沙星提供了这些最小选择浓度。
