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

Abstract

BackgroundHaemophilus 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.ResultsMICs 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 AUC24h/MIC, AUC24h/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 R2 of 0.9928 and 0.9911, respectively. The target values of 3-log10-unit and 4-log10-unit reduction for AUC24h/MPC were 33 and 42, while the same efficacy for AUC24h/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).ConclusionsThe PK/PD surrogate markers AUC24h/MIC, Cmax/MIC and AUC24h/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.

Pharmacokinetic and Pharmacodynamic Evaluation of Marbofloxacin and PK/PD Modeling against Escherichia coli in Pigs

“…Furthermore, the measurement at the infection site for PK and PD was a preferred method to analyze and correlate PK/PD modeling ( Liu et al, 2002 ; Mouton et al, 2008 ). The PK of drug concentrations was investigated in serum as the ex vivo data in most published PK/PD modeling studies, and there were also studies for MBF against Haemophilus parasuis and Pasteurella multocida in beagle, sheep, calves, turtles, broiler chicken, pigs, and so on ( Sidhu et al, 2010 ; Vallé et al, 2012 ; Potter et al, 2013 ; Qu et al, 2015 ; Sun et al, 2015 ; Yohannes et al, 2015 ). However, the PK of MBF in the ileum content which was the target infection site by E. coli of pigs was the first to investigate using ileac cannulation.…”

“…There were differences in the immune status of target animals and pathogens. The published AUC 0-24 h /MIC was 46 h for bactericidal action in PK/PD study of MBF against Mannheimia haemolytica , and 88 h for the bactericidal action of MBF against Haemophilus parasuis ( Aliabadi and Lees, 2002 ; Sun et al, 2015 ). Therefore, it was of great importance to study the PK/PD indices of fluoroquinolones including MBF individually.…”

“…The pharmacokinetics (PK) of MBF has been investigated in various livestock such as goats, cows, cats, sheep, pigs, and dogs ( Waxman et al, 2001 ; Schneider et al, 2004 ; Albarellos et al, 2005 ; Ding et al, 2010 ; Sidhu et al, 2010 ), showing a high concentration in plasma and peripheral tissue, with up to 100% bioavailability, and wide and rapid distribution in tissues. Previous studies have shown MBF to have excellent pharmacokinetic characteristics such as being well-absorbed after oral and parenteral administration, higher concentrations in tissues than in the plasma, and weakly bound to plasma proteins (<10%) ( Haritova et al, 2006 ; Andraud et al, 2011 ; Sun et al, 2015 ). MBF is distributed widely throughout the animals’ bodies, which could reach 1.6 times higher drug concentrations in the skin than in the plasma in dogs, and MBF concentrations in the plasma can remain above the MIC (>24 h) longer than the dose density ( Cester et al, 1996 ; Schneider et al, 1996 ).…”

Pharmacokinetic and Pharmacodynamic Evaluation of Marbofloxacin in Pig against Korean Local Isolates ofActinobacillus pleuropneumoniae

“…Furthermore, the PK/PD indices of the same drug against different pathogens also vary. So, it is of great importance to study the PK/PD indices of fluoroquinolones against individual pathogen [41]. In the current study, the PK data obtained from a single i.v., i.m., and p.o.…”

Epidemiological and PK/PD cutoff values determination and PK/PD-based dose assessment of gamithromycin against Haemophilus parasuis in piglets

“…We isolated 192 clinical H. parasuis strains from heart, lung, brain, peritoneum, pericardial sac and joint fluids of diseased swine suffering polyserositis, pneumonia or meningitis in five different provinces of China in 2010 to 2018. A well-characterized representative strain of H. parasuis LM15 (serotype 5) was used for ex vivo timekill experiments and PK/PD modeling because serotype 5 is the primary serotype found in China [3,28,29]. Species identification was performed by using MALDI-TOF mass systems (Axima-Assurance-Shimadzu) as previously described [30].…”