A Pharmacokinetic-Pharmacodynamic Approach to Propose an Amoxicillin Dosage Regimen for Treatment of Escherichia coli and Staphylococcus delphini Infections in Mink (Neovison vison)

The aim of this study was to develop amoxicillin (AMX) dosage regimens for the treatment of Escherichia coli and Staphylococcus delphini infections in mink using a pharmacokinetic (PK) and pharmacodynamic (PD) approach. Two animal experiments with a total of 12 minks were conducted to investigate PK parameters after intravenous or oral administration of an AMX off-label dosage of 15 mg/kg. The PK characteristics of AMX were analyzed using non-linear mixed effect modeling. In vitro time kill experiments using AMX concentrations up to 16 × MIC were conducted with two E. coli and two S. delphini isolates. Semi-mechanistic modeling of time-kill experiments was subsequently done to study PD characteristics. By integrating PK and PD data, the PK/PD index and PK/PD target were predicted. Simulations were applied to determine an optimal AMX dosage. The PD model revealed higher in vitro efficacy and lower potency of AMX against E. coli compared to S. delphini. fT(%) > MIC was selected as the PK/PD index, indicating a time-dependent effect of AMX. New mink-specific AMX dosages of 50 mg/kg twice a day for E. coli infections and 7.5 mg/kg once daily for S. delphini infections were determined. The study emphasizes the need for dose optimization studies, especially for minor animal species for which antibiotics are generally used off-label.