Burch D G S, Sperling D
Octagon Services Ltd, Windsor, Berkshire, UK.
Ceva Sante Animale, Libourne Cedex, Bordeaux, France.
J Vet Pharmacol Ther. 2018 Jun;41(3):356-368. doi: 10.1111/jvp.12482. Epub 2018 Jan 19.
Amoxicillin has become a major antimicrobial substance in pig medicine for the treatment and control of severe, systemic infections such as Streptococcus suis. The minimum inhibitory concentration 90% (MIC 90) is 0.06 μg amoxicillin/ml, and the proposed epidemiological cut-off value (ECOFF) is 0.5 μg/ml, giving only 0.7% of isolates above the ECOFF or of reduced susceptibility. Clinical breakpoints have not been set for amoxicillin against porcine pathogens yet, hence the use of ECOFFs. It has also been successfully used for bacterial respiratory infections caused by Actinobacillus pleuropneumoniae and Pasteurella multocida. The ECOFF for amoxicillin against A. pleuropneumoniae is also 0.5 μg/ml demonstrating only a reduced susceptibility in 11.3% of isolates. Similarly, P. multocida had an ECOFF of 1.0 μg/ml and a reduced susceptibility in only 2.6% of isolates. This reduced susceptibility disappears when combined with the beta-lactamase inhibitor, clavulanic acid, demonstrating that it is primarily associated with beta-lactamase production. In contrast, amoxicillin is active against Escherichia coli and Salmonella species but using ECOFFs of 8.0 and 4.0 μg/ml, respectively, reduced susceptibility can be seen in 70.9% and 67.7% of isolates. These high levels of reduced susceptibility are primarily due to beta-lactamase production also, and most of this resistance can be overcome by the combination of amoxicillin with clavulanic acid. Currently, amoxicillin alone is considered an extremely valuable antimicrobial in both human and animal medicine and remains in the critically important category of antibiotics alongside the fluoroquinolones and macrolides by the World Health Organization as well as the third- and fourth-generation cephalosporins, but these cephalosporins show marked resistance to basic beta-lactamase production and are only destroyed by the extended-spectrum beta-lactamases. Amoxicillin alone and in combination with clavulanic acid are currently classed together in Category 2 in the European Union. By reviewing the pharmacodynamic data and comparing this with pharmacokinetic data from healthy and infected animals and clinical trial data, it can be seen that the product has a good efficacy against S. suis and A. pleuropneumoniae, in spite of usage over many years. However, it may be much less efficacious on its own against E. coli, due to reduced susceptibility and resistance associated with beta-lactamase production, which is largely overcome by the use of clavulanic acid. It is felt that this differentiation may be useful in future classification of amoxicillin alone, in comparison with its combined use with clavulanic acid and thereby preserve the use of the more critically important antibiotics in veterinary medicine and reducing the risk of their resistance being transmitted to human.
阿莫西林已成为猪用药物中治疗和控制严重全身性感染（如猪链球菌感染）的主要抗菌物质。其90%的最小抑菌浓度（MIC90）为0.06 μg阿莫西林/毫升，建议的流行病学临界值（ECOFF）为0.5 μg/毫升，只有0.7%的分离株高于该临界值或对阿莫西林敏感性降低。目前尚未设定阿莫西林针对猪病原体的临床断点，因此采用了ECOFF。它也已成功用于治疗由胸膜肺炎放线杆菌和多杀性巴氏杆菌引起的细菌性呼吸道感染。阿莫西林针对胸膜肺炎放线杆菌的ECOFF同样为0.5 μg/毫升，仅11.3%的分离株对其敏感性降低。同样，多杀性巴氏杆菌的ECOFF为1.0 μg/毫升，仅2.6%的分离株对其敏感性降低。当与β-内酰胺酶抑制剂克拉维酸联合使用时，这种敏感性降低现象消失，表明其主要与β-内酰胺酶的产生有关。相比之下，阿莫西林对大肠杆菌和沙门氏菌属有活性，但分别采用8.0和4.0 μg/毫升的ECOFF时，70.9%和67.7%的分离株对其敏感性降低。这些高比例的敏感性降低同样主要归因于β-内酰胺酶的产生，且阿莫西林与克拉维酸联合使用可克服大部分此类耐药性。目前，阿莫西林单独使用在人类和兽医学中都被认为是一种极其有价值的抗菌药物，世界卫生组织将其与氟喹诺酮类和大环内酯类抗生素以及第三代和第四代头孢菌素一起列为极其重要的抗生素类别，但这些头孢菌素对基本的β-内酰胺酶产生有明显耐药性，仅被超广谱β-内酰胺酶破坏。在欧盟，阿莫西林单独使用及其与克拉维酸联合使用目前都被归为第2类。通过回顾药效学数据，并将其与健康动物和感染动物的药代动力学数据以及临床试验数据进行比较，可以看出，尽管阿莫西林已使用多年，但该产品对猪链球菌和胸膜肺炎放线杆菌仍有良好疗效。然而，由于与β-内酰胺酶产生相关的敏感性降低和耐药性，阿莫西林单独使用时对大肠杆菌的疗效可能会低得多，而使用克拉维酸可在很大程度上克服这一问题。人们认为，这种差异在未来对阿莫西林单独使用的分类中可能会很有用，与它和克拉维酸联合使用的情况相比，并由此保留兽医学中更重要的抗生素的使用，降低其耐药性传播给人类的风险。
