The Vehicle of Administration and Prandial State May Reduce the Spectrum of Oral Broad-Spectrum Antibiotics (Oxytetracycline, Fosfomycin and Amoxicillin) Administered to Piglets: A Pharmacokinetic/Pharmacodynamic Approach
Corresponding Author
Julieta M. Decundo
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
Correspondence:
Julieta M. Decundo ([email protected])
Search for more papers by this authorSusana N. Dieguez
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
Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CIC-PBA), La Plata, Argentina
Search for more papers by this authorGuadalupe Martínez
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
Search for more papers by this authorFabián A. Amanto
Área de Producción Porcina, Departamento de Producción Animal, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires, Tandil, Argentina
Search for more papers by this authorDenisa S. Pérez Gaudio
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
Search for more papers by this authorAlejandro L. Soraci
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
Search for more papers by this authorCorresponding Author
Julieta M. Decundo
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
Correspondence:
Julieta M. Decundo ([email protected])
Search for more papers by this authorSusana N. Dieguez
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
Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CIC-PBA), La Plata, Argentina
Search for more papers by this authorGuadalupe Martínez
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
Search for more papers by this authorFabián A. Amanto
Área de Producción Porcina, Departamento de Producción Animal, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires, Tandil, Argentina
Search for more papers by this authorDenisa S. Pérez Gaudio
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
Search for more papers by this authorAlejandro L. Soraci
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
Search for more papers by this authorFunding: This work was supported by CIVETAN-CONICET.
ABSTRACT
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.
Conflicts of Interest
The authors declare no conflicts of interest.
Open Research
Data Availability Statement
Data that support this work are available from the corresponding author upon reasonable request.
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