AUTHOR=Wang Jianyi , Hao Haihong , Huang Lingli , Liu Zhenli , Chen Dongmei , Yuan Zonghui 

TITLE=Pharmacokinetic and Pharmacodynamic Integration and Modeling of Enrofloxacin in Swine for Escherichia coli

JOURNAL=Frontiers in Microbiology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2016.00036

DOI=10.3389/fmicb.2016.00036

ISSN=1664-302X

ABSTRACT=<p>The aim of this study was to optimize the dose regimens of enrofloxacin to reduce the development of fluoroquinolone resistance in <italic>Escherichia coli</italic> (<italic>E.</italic>coli) using pharmacokinetic/pharmacodynamic (PK/PD) modeling approach. The single dose (2.5 mg/kg body weight) of enrofloxacin was administered intramuscularly (IM) to the healthy pigs. Using cannulation, the pharmacokinetic properties, including peak concentration (<italic>C</italic><sub>max</sub>), time to reach <italic>C</italic><sub>max</sub> (<italic>T</italic><sub>max</sub>), and area under the curve (AUC), were determined in plasma and ileum content. The <italic>C</italic><sub>max</sub>, <italic>T</italic><sub>max</sub>, and AUC in the plasma were 1.09 ± 0.11 μg/mL, 1.27 ± 0.35 h, and 12.70 ± 2.72 μg·h/mL, respectively. While in ileum content, the <italic>C</italic><sub>max</sub>, <italic>T</italic><sub>max</sub>, and AUC were 7.07 ± 0.26 μg/mL, 5.54 ± 0.42 h, and 136.18 ± 12.50 μg·h/mL, respectively. Based on the minimum inhibitory concentration (MIC) data of 918 <italic>E. coli</italic> isolates, an <italic>E. coli</italic> O<sub>101</sub>/K<sub>99</sub> strain (enrofloxacin MIC = 0.25 μg/mL) was selected for pharmacodynamic studies. The <italic>in vitro</italic> minimum bactericidal concentration (MBC), mutant prevention concentration (MPC), and <italic>ex vivo</italic> time-killing curves for enrofloxacin in ileum content were established against the selected <italic>E. coli</italic> O<sub>101</sub>/K<sub>99</sub> strain. Integrating the <italic>in vivo</italic> pharmacokinetic data and <italic>ex vivo</italic> pharmacodynamic data, a sigmoid <italic>E</italic><sub>max</sub> (Hill) equation was established to provide values for ileum content of AUC<sub>24h</sub>/MIC producing, bactericidal activity (52.65 h), and virtual eradication of bacteria (78.06 h). A dosage regimen of 1.96 mg/kg every 12 h for 3 days should be sufficient in the treatment of <italic>E. coli</italic>.</p>