Pharmacokinetic/pharmacodynamic relationships of enrofloxacin against Klebsiella pneumoniae in an in vivo infection model in young chicks.

Abstract

Klebsiella pneumoniae is a serious pathogenic bacterium that poses a significant threat to young poultry and the cause of significant chick mortality and economic loss. We investigated the therapeutic efficacy of enrofloxacin in treating K. pneumoniae infections in chicks and employed an in vivo pharmacokinetic/pharmacodynamic (PK/PD) model. In vivo efficacy was evaluated using 6 multiple-dose groups (oral administration once a day for 3 d) and 2 single-dose groups (oral administration once only). The PK and PD parameters of plasma and lung were analyzed using PK/PD fitting analysis. K. pneumoniae administered intratracheally (10CFU/mL in 0.4 mL saline) was used to establish a model for pulmonary infection. The plasma protein binding of enrofloxacin was 20.18%. Enrofloxacin displayed Tvalues of 4.78 ± 0.69 h and 4.78 ± 1.02 h in plasma and lung of infected chicks, respectively. When the dosage in the multiple-dose group was > 10 mg/kg, bactericidal activity was found and complete eradication was not achieved when the dosage was ≤ 40 mg/kg. When Twas set at 20%, the calculated dosage and bacterial reduction (E) based on plasma free drug data were 4.03 mg/kg and -1.982 LogCFU/mL, respectively. In the calculation of PK/PD parameters for reducing 3 LogCFU/mL and using C/MIC, AUC/MIC and Tof free drug in plasma values at 9.479, 379.691, and 44.395%, respectively, the value of AUC/MIC based on the concentration of drug in lung was 530.800. According to the fitting correlation R, the PK/PD fitting results of free drug in plasma were better. The corresponding enrofloxacin dosage for AUC/MIC of the plasma free drug concentration was 14.16 mg/kg. The administration regimen corresponding to these dosages was once daily for 3 d. This dosage regimen (14.16 mg/kg) was relatively high compared to the clinically recommended dosage in China (7.5 mg/kg) when treating infections caused by K. pneumoniae with MIC ≥ 0.125 μg/mL, so careful consideration is needed.