Decundo Julieta M, Dieguez Susana N, Martínez Guadalupe, Amanto Fabián A, Pérez Gaudio Denisa S, Soraci Alejandro L
Laboratorio de Toxicología, Departamento de Fisiopatología, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires, Tandil, Argentina.
Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN, UNCPBA-CICPBA-CONICET), Tandil, Argentina.
J Vet Pharmacol Ther. 2025 Jan;48(1):37-43. doi: 10.1111/jvp.13479. Epub 2024 Aug 30.
The objective of this study was to assess the impact of the vehicle of administration and the prandial state of post weaning piglets on the indices of therapeutic efficacy for different broad-spectrum antibiotic/pathogen combinations. Pharmacokinetic data were retrieved from previous studies, in which we orally administered oxytetracycline (OTC), fosfomycin (FOS), or amoxicillin (AMX) according to the following treatments: dissolved in soft water to fasted or non-fasted piglets, dissolved in hard water to fasted or non-fasted piglets, and mixed with feed. Minimum inhibitory concentration (MIC) values for susceptible strains of bacteria causing swine diseases were obtained from the database of European Committee on Antimicrobial Susceptibility Testing (EUCAST) for each antibiotic. Pharmacokinetic/pharmacodynamic (PK/PD) indices of therapeutic efficacy-drug exposure over the dosing interval (fAUC/MIC) for OTC and FOS; time that free drug concentration remains above MIC (%fT>MIC) for AMX-were calculated for each antibiotic/pathogen combination under each treatment. After all OTC and in-feed FOS and AMX treatments, the indices of therapeutic efficacy were below the target value for all the study microorganisms. When FOS or AMX were delivered dissolved in soft or hard water, the indices were above the target value over which therapeutic efficacy would be expected for Escherichia coli treated with FOS and, Glaesserella parasuis, Pasteurella multocida, and Actinobacillus pleuropneumoniae treated with AMX. The prandial state of piglets showed no influence on the indices of therapeutic efficacy. Pharmacokinetic profiles of broad-spectrum antibiotics, specifically the ability to achieve target concentrations, may be largely reduced due to drug interactions with components present in feed or water resulting in a discrepancy with PK/PD principles of prudent and responsible use of antibiotics.
本研究的目的是评估给药载体和断奶后仔猪的进食状态对不同广谱抗生素/病原体组合治疗效果指标的影响。药代动力学数据取自先前的研究，在这些研究中，我们根据以下处理方式口服土霉素（OTC）、磷霉素（FOS）或阿莫西林（AMX）：溶解于软水后给禁食或非禁食仔猪服用，溶解于硬水后给禁食或非禁食仔猪服用，以及与饲料混合。每种抗生素对引起猪病的敏感菌株的最低抑菌浓度（MIC）值取自欧洲抗菌药物敏感性试验委员会（EUCAST）的数据库。针对每种处理下的每种抗生素/病原体组合，计算了治疗效果的药代动力学/药效学（PK/PD）指标——给药间隔期间的药物暴露量（fAUC/MIC）（针对OTC和FOS）；游离药物浓度保持高于MIC的时间（%fT>MIC）（针对AMX）。在所有OTC以及饲料中添加FOS和AMX的处理后，所有研究微生物的治疗效果指标均低于目标值。当FOS或AMX溶解于软水或硬水给药时，对于用FOS治疗的大肠杆菌以及用AMX治疗副猪嗜血杆菌、多杀性巴氏杆菌和胸膜肺炎放线杆菌而言，这些指标高于预期产生治疗效果的目标值。仔猪的进食状态对治疗效果指标没有影响。由于药物与饲料或水中的成分发生相互作用，广谱抗生素的药代动力学特征，特别是达到目标浓度的能力，可能会大幅降低，从而导致与谨慎和合理使用抗生素的PK/PD原则出现偏差。
