title: In vitro Dynamic Pharmacokinetic/Pharmacodynamic (PK/PD) study and COPD of Marbofloxacin against Haemophilus parasuis.
abstract: BACKGROUND
  Haemophilus parasuis (H. parasuis) can invade the body and cause systemic infection under stress conditions. Marbofloxacin has been recommended for the treatment of swine infections. However, few studies have investigated the PK/PD characteristics and PK/PD cutoff (COPD) of this drug against H. parasuis.
  
  
  RESULTS
  MICs of marbofloxacin against 198 H. parasuis isolates were determined. The MIC50 and MIC90 were 2 and 8 mg/L, respectively. An in vitro dynamic PK/PD model was established to study the PK/PD relationship of marbofloxacin against H. parasuis. The PK/PD surrogate markers Cmax/MIC, Cmax/MPC (the maximum concentration divided by MIC or mutant prevention concentration (MPC)) and AUC 24h/MIC, AUC 24h/MPC (the area under the curve during the first 24 h divided by MIC or MPC) simulated the antimicrobial effect of marbofloxacin successfully with the R(2) of 0.9928 and 0.9911, respectively. The target values of 3-log10-unit and 4-log10-unit reduction for AUC 24h/MPC were 33 and 42, while the same efficacy for AUC 24h/MIC were 88 and 110. The COPD deduced from Monte Carlo simulation (MCS) for marbofloxacin against H. parasuis was 0.5 mg/L. The recommended dose of marbofloxacin against H. parasuis with MIC ≤ 2 mg/L was 16 mg/kg body weight (BW).
  
  
  CONCLUSIONS
  The PK/PD surrogate markers AUC 24h/MIC, Cmax/MIC and AUC 24h/MPC, Cmax/MPC properly described the effects of marbofloxacin. Marbofloxacin can achieve the best efficacy at dosage of 16 mg/kg BW for strains with MIC values ≤ 2 mg/L, therefore, it is obligatory to know the sensitivity of the pathogen and to treat animals as early as possible. The very first COPD provide fundamental data for marbofloxacin breakpoint determination.
authors.affiliation: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China. jiansun@scau.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China. xiami87107@sina.com.|Jiangsu Co-Innovation Centre for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, People's Republic of China. xiami87107@sina.com.
authors.forename: Xia
authors.initials: X
authors.lastname: Xiao
authors.affiliation: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China. 604284914@qq.com.
authors.forename: Rui-Juan
authors.initials: RJ
authors.lastname: Huang
authors.affiliation: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China. 731232633@qq.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.affiliation: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China. 153787903@qq.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China. 290227387@qq.com.
authors.forename: Xi
authors.initials: X
authors.lastname: Fang
authors.affiliation: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China. 973132242@qq.com.
authors.forename: Ting
authors.initials: T
authors.lastname: Huang
authors.affiliation: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China. 87647314@qq.com.
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Zhou
authors.affiliation: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China. gale@scau.edu.cn.|Jiangsu Co-Innovation Centre for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, People's Republic of China. gale@scau.edu.cn.
authors.forename: Ya-Hong
authors.initials: YH
authors.lastname: Liu
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D024841:Fluoroquinolones / Q000493:pharmacokinetics* / Q000494:pharmacology*; D044137:Haemophilus parasuis / Q000187:drug effects*; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D009010:Monte Carlo Method
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; C080260:marbofloxacin