Pharmacokinetic/pharmacodynamic evaluation of marbofloxacin in the treatment of Haemophilus parasuis and Actinobacillus pleuropneumoniae infections in nursery and fattener pigs using Monte Carlo simulations

Abstract

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Vilalta, C., Giboin, H., Schneider, M., El Garch, F., Fraile, L. Pharmacokinetic/ pharmacodynamic evaluation of marbofloxacin in the treatment of Haemophilus parasuis and Actinobacillus pleuropneumoniae infections in nursery and fattener pigs using Monte Carlo simulations. J. vet. Pharmacol. Therap. 37, 542-549. This study evaluated the theoretical clinical outcome of three marbofloxacin posology regimens in two groups of pigs (weaners and fatteners) for the treatment of Actinobacillus pleuropneumoniae (App) and Haemophilus parasuis (Hp) infection and the appearance of resistant bacteria due to the antibiotic treatment. The probability of target attainment (PTA) for pharmacokinetic/phar-macodynamics (PK/PD) ratios associated with clinical efficacy and with the appearance of antimicrobial resistance for fluoroquinolones at each minimum inhibitory concentration (MIC) or mutant prevention concentration (MPC) were calculated, respectively. The cumulative fraction of response (CFR) was calculated for the three posology regimens against App and they ranged from 91.12% to 96.37% in weaners and from 93% to 97.43% in fatteners, respectively. In the case of Hp, they ranged from 80.52% to 85.14% in weaners and from 82.01% to 88.49% in fatteners, respectively. Regarding the PTA of the PK/PD threshold associated with the appearance of antimicrobial resistance , results showed that marbofloxacin would prevent resistances in most of the animals up to the MPC value of 1 lg/mL.

Randomised controlled field study to evaluate the efficacy and clinical safety of a single 8 mg/kg injectable dose of marbofloxacin compared with one or two doses of 7.5 mg/kg injectable enrofloxacin for the treatment of Actinobacillus pleuropneumoniae infections in growing-fattening pigs in Europe

“…MIC) within populations of microorganism may influence efficacy and the potential for resistance development in the target pathogen. Simulations of this variability in PK-PD have been used to evaluate marbofloxacin in the treatment of APP infections in nursery and fattening pigs, and showed that a single dose of 8 mg/kg would provide robust efficacy and minimise resistance development in APP with MICs of 0.03–0.12 μg/mL [9, 10] which are comparable to the APP MIC range reported here.…”

Survey of susceptibility to marbofloxacin in bacteria isolated from diseased pigs in Europe

“…These data should be analysed alongside antimicrobial pharmacokinetic data, which can be variable from one animal to another. Vilalta and others (2014) calculated, from a Monte Carlo simulation, the probability of PKPD target attainment taking into account the variability of drug exposure in pigs and the variability of MICs from respiratory bacterial isolates. This study also reported the cumulative fractions of response for several dosing schemes, meaning the proportion of animals in the population achieving a PKPD threshold values taking into account both the MIC distribution against the bacteria and the PK parameter distribution in the population.…”

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

“…[2]. Its properties of rapid absorption, good distribution, and broad spectrum against most of the swine respiratory pathogens, such as Haemophilus parasuis and Actinobacillus pleuropneumoniae , make it a good candidate to deal with a respiratory outbreak caused by any of these pathogens [3]. A. pleuropneumoniae is the causative agent of porcine pleuropneumonia, a worldwide disease with occasional clinical outbreaks that can have a severe economic impact [4].…”

“…The pharmacokinetics of marbofloxacin have been investigated in different animals and it demonstrated an almost 100% bioavailability, higher concentration in plasma and peripheral tissues in goats [17], cows [18], cats [19], sheep [20], dogs [21], and pigs [22, 23]. Although, some studies have been published on the pharmacokinetics of marbofloxacin in animals including pigs [3, 18–22, 24, 25], yet the pharmacokinetic data of marbofloxacin in pig tissues and plasma is not sufficient enough to predict the efficacy of this drug precisely. Furthermore, the integration of pharmacokinetic (PK) data with pharmacodynamic (PD) data helps to establish the PK/PD indices (AUC/MIC, C max /MIC, T > MIC, AUC > MIC, etc.,) which are fundamental to predict efficacy and minimize resistance development [26, 27].…”