S. Soback

National Residue Control Laboratory, Kimron Veterinary Institute, Beit Dagan, Israel

Introduction: The first antimicrobial agents were introduced to human therapy in the mid-30s (sulfonamides) and during WW2 (penicillin). The use of these drugs in veterinary therapy followed soon after. Tetracycline was introduced in 1954. These 3 classes would remain the most used antimicrobial classes in farm animal therapy up to this day. The number of other drug molecules available to farm animal practitioners is decreasing and novel molecules are not entering the market. Antimicrobial resistance reduction has been established as the top priority in management antimicrobial therapy. By modern standards, scientifically sound therapy must be based on bacterial susceptibility profile, accurate PK/PD principles and solid efficacy trials. It must also fit the regulatory demands and policy. These two requirements are often very difficult to combine. This presentation aims at characterizing the issues raising from antimicrobial use both in humans and animals over time and evaluate the suggested and optional solutions to these issues especially in farm animals.

Patients and Methods: Farm animals represent the potential treatment groups. The methods related to various issues of antimicrobial treatment, such as resistance monitoring, pharmacokinetics, residue control etc. and their contribution to potential improvement of therapy was validated.

Results: Lack of pharmacological technology and analytical techniques almost derailed the introduction of these drugs as therapeutic agents. There were no reliable analytical techniques available for accurate determination of basic pharmacokinetic parameters. Pharmacokinetic theory has undergone significant development after the introduction of the above antimicrobials. Resistance and the mechanisms causing resistance were difficult to study at the time, but can be understood at molecular level today. Residues were initially not a consideration, but developed into a major issue much later. It took decades to develop even pseudoscientific residue detection methods. In short, none of the factors impacting drug approval according to modern criterions were investigated and included in the original applications. Residues were later added to the approval, efficacy much less.

Conclusions: The “One Health” initiative is strongly based on usage reduction of these drugs. In this, companion animal antimicrobial therapy is very similar to human therapy. The selected tools to improve antimicrobial use are volume reduction and use pattern (compound selection) modification. In production animals, beyond quantifiable reduced use, serious limitations up to complete ban on usage of the more modern antimicrobials have been employed. Critical scientific research of the comprehensive qualitative and quantitative effects of these interventions is essential for any future progress.

中文翻译：

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I10 | 抗菌疗法的发展：问题和解决方案

S.索巴克

国家残留物控制实验室，Kimron 兽医研究所，拜特达甘，以色列

介绍：第一种抗菌剂在 20 世纪 30 年代中期（磺胺类药物）和二战期间（青霉素）被引入人类治疗。不久之后，这些药物就被用于兽医治疗。四环素于 1954 年问世。直到今天，这 3 个类别仍是农场动物治疗中最常用的抗菌类别。可供农场动物从业者使用的其他药物分子的数量正在减少，新分子也没有进入市场。降低抗菌素耐药性已被确定为管理抗菌素治疗的重中之重。按照现代标准，科学合理的治疗必须基于细菌敏感性特征、准确的 PK/PD 原则和可靠的疗效试验。它还必须符合监管要求和政策。这两个要求通常很难结合起来。

患者和方法：农场动物代表潜在的治疗组。验证了与抗微生物治疗的各种问题相关的方法，例如耐药性监测、药代动力学、残留控制等，以及它们对治疗潜在改进的贡献。

结果：缺乏药理学技术和分析技术几乎使这些药物作为治疗剂的引入脱轨。没有可靠的分析技术可用于准确测定基本药代动力学参数。引入上述抗微生物剂后，药代动力学理论有了重大发展。耐药性和导致耐药的机制在当时很难研究，但今天可以在分子水平上理解。残留物最初不是考虑因素，但后来发展成为一个主要问题。即使是伪科学的残留物检测方法也需要数十年的时间才能开发出来。简而言之，根据现代标准，影响药品批准的因素均未被调查并包含在原始申请中。残留物后来被添加到批准中，

结论： “One Health”倡议主要基于减少这些药物的使用。在这一点上，伴侣动物的抗菌疗法与人类疗法非常相似。选定的改进抗菌药物使用的工具是减少体积和修改使用模式（化合物选择）。在生产动物中，除了可量化的减少使用外，还采用了严重的限制措施，直至完全禁止使用更现代的抗菌药物。对这些干预措施的综合定性和定量影响进行批判性科学研究对于未来的任何进展都是必不可少的。