Murine Thigh Microdialysis to Evaluate the Pharmacokinetic/Pharmacodynamic Integration of Cefquinome Against Actinobacillus pleuropneumoniae

Abstract

This study aimed to explore the application of microdialysis in pharmacokinetic (PK)/pharmacodynamic (PD) integration of cefquinome against Actinobacillus pleuropneumoniae. After the A. pleuropneumoniae population reached 10 6 CFU/thigh, the mice received 0.04, 0.16, 0.63, 2.5, and 10 mg/kg cefquinome by subcutaneous injection. Plasma samples were collected by retro-orbital puncture for 4 h, and thigh dialysate was obtained by microdialysis at a flow rate of 1.5 µL/min for 6 h for the PK study. For the PD experiment, the infected mice were treated with a 4-fold-increase in the total cefquinome dose, ranging from 0.01 to 10 mg/kg/24 h, divided into one, two, three, four, and eight doses. The number of bacteria was determined and an inhibitory sigmoid maximum effect (E max) model was used to analyse the relationships between PK/PD parameters and efficacy. The mean penetration of cefquinome from plasma to the thigh was 0.591. The PK data for PK/PD integration were obtained by extrapolation. The fittest PK/PD parameter for efficacy evaluation was %fT>MIC (the percentage of time that free drug concentrations exceed the MIC). The magnitudes of %fT>MIC to achieve net bacterial stasis, 1-log 10 CFU reduction, 2-log 10 CFU reduction, and 3-log 10 CFU reduction were 19.56, 28.65, 41.59, and 67.07 % in plasma and 21.74, 36.11, 52.96, and 82.68% in murine thigh, respectively. Microdialysis was first applied to evaluate the PK/PD integration of cefquinome against A. pleuropneumoniae. These results would provide valuable references when we apply microdialysis to study the PK/PD integration model and use cefquinome to treat animal diseases caused by A. pleuropneumoniae.

Lung microdialysis and in vivo PK/PD integration of cefquinome against Actinobacillus pleuropneumoniae in a porcine experimental lung infection model

“…Using an inhibitory Sigmoid E max model, the % f T > MIC values required for achieving bacterial growth inhibition as well as 1, 2 and 3 log 10 CFU/g reductions in the lung of infected pigs were 22.45, 28.86, 37.62 and 56.46%, respectively. The antimicrobial efficacy of cefquinome against A. pleuropneumoniae , as assessed using a neutropenic murine thigh infection model, showed that the % f T > MIC values required for achieving bacterial stasis and 1 and 2 log 10 CFU reductions were 31.61, 38.48 and 54.01%, respectively ( 33 ). In the neutropenic murine thigh infection model, the % f T > MIC values required to achieve the same antimicrobial efficacy are higher than those in the porcine experimental lung infection model.…”

Pharmacokinetics of tilmicosin in chicken joints based on a novel microdialysis sampling method

“…The PKs of tilmicosin were determined in SPF chickens administered 15 mg/kg tilmicosin and we identified a T max of 1.50 h and t 1/2 of 20.10 h in plasma similar to other study results. For example, healthy chickens were administered 7.5 mg/kg tilmicosin orally resulted in a t 1/2 value of 22.67 h and a T max of 1 h (Zhang, Zhou, et al, 2020). Tilmicosin given orally at 15 mg/kg to broiler chickens resulted in a T max of 3 h and t 1/2 of 32 h (Dimitrova et al, 2012).…”

“…The in vitro recovery of tilmicosin was determined by dialysis and retrodialysis as previously described (Zhang, Zhou, et al, 2020). In brief, 500 ng/mL tilmicosin was provided at flow rates of 0.5, 1.0, 1.5 and 2.0 μL/min to ascertain the optimal perfusion rate.…”

Pharmacokinetic/Pharmacodynamic Relationships of Tulathromycin Against Actinobacillus pleuropneumoniae in a Porcine Tissue Cage Infection Model

“…The bacteria were grown as previously described ( 27 ) except that different media were used. Briefly, the bacterial were grown in supplemented TSB and TSA (see above).…”