In vitro Dynamic Pharmacokinetic/Pharamcodynamic (PK/PD) study and CO(PD) of Marbofloxacin against Haemophilus parasuis

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 (CO(PD)) of this drug against H. parasuis. RESULTS: MICs of marbofloxacin against 198 H. parasuis isolates were determined. The MIC(50) and MIC(90) 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 C(max)/MIC, C(max)/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-log(10)-unit and 4-log(10)-unit reduction for AUC(24h)/MPC were 33 and 42, while the same efficacy for AUC(24h)/MIC were 88 and 110. The CO(PD) 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, C(max)/MIC and AUC(24h)/MPC, C(max)/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 CO(PD) provide fundamental data for marbofloxacin breakpoint determination.