In vivo antimicrobial activity of marbofloxacin against Pasteurella multocida in a tissue cage model in calves

Abstract

Marbofloxacin is a fluoroquinolone specially developed for use in veterinary medicine with broad-spectrum antibacterial activity. The objective of our study was to re-evaluate in vivo antimicrobial activity of marbofloxacin against Pasteurella multocida using subcutaneously implanted tissue cages in calves. Calves were infected by direct injection into tissue cages with P. multocida(type B, serotype 2), then intramuscularly received a range of marbofloxacin doses 24 h after inoculation. The ratio of 24 h area under the concentration-time curve divided by the minimum inhibitory concentration or the mutant prevention concentration (AUC24 h/MIC or AUC24 h/MPC) was the pharmacokinetic-pharmacodynamic (PK/PD) index that best described the effectiveness of marbofloxacin against P. multocida (R2 = 0.8514) by non-linear regression analysis. Marbofloxacin exhibited a good antimicrobial activity in vivo. The levels of AUC24 h/MIC and AUC24 h/MPC that produced 50% (1.5log10 CFU/mL reduction) and 90% (3log10 CFU/mL reduction) of maximum response were 18.60 and 50.65 h, 4.67 and 12.89 h by using sigmoid Emax model WINNONLIN software, respectively. The in vivo PK/PD integrated methods by tissue cage model display the advantage of the evaluation of antimicrobial activity and the optimization of the dosage regimen for antibiotics in the presence of the host defenses, especially in target animal of veterinary interest.

Integrated pharmacokinetic–Pharmacodynamic (PK/PD) model to evaluate the in vivo antimicrobial activity of Marbofloxacin against Pasteurella multocida in piglets

“…Marbofloxacin shows excellent effectiveness for treating P. multocida infection through in vitro tests [16]. The protein binding of marbofloxacin was low in previous studies and was 52% for serum, 40% for tissue cage fluid in cattle and 49.4% for pig serum [3, 16]. Only free drug in the interstitial fluid is microbiologically active against extracellular bacteria [3, 27].…”

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

“…There is a continuous exposure to a fixed concentration of the agent for a defined duration (e.g., 24 h) in an ex vivo model, whereas a gradient of concentration in the dynamic in vitro model. The level of AUC 24h /MPC (33 for 3 log 10 reductions) was higher than that (12.89 for bactericidal effect) resulted from a tissue cage model of marbofloxacin against Pasteurella multocida [ 26 ]. The greatest influence for the differences might be the immune status of the animal.…”

Pharmacokinetics, milk penetration and PK/PD analysis by Monte Carlo simulation of marbofloxacin, after intravenous and intramuscular administration to lactating goats

“…The use of PK/PD approach is an essential tool in the rational selection of dosage regimens of antimicrobial agents, allowing for the development of safe and effective antimicrobial protocols, minimizing the emergence of resistance and its further spread to the animal and human populations, as well as promoting the prudent use of antimicrobials (Papich, ; Toutain, Del Castillo, & Bousquet‐Mélou, ; Ungemach, Muller‐Bahrdt, & Abraham, ). Fluoroquinolones are concentration‐dependent antimicrobials, C max /MIC and AUC 24 /MIC ratios showed to be the best predictors of clinical outcome and bacterial eradication in many studies performed in humans and animals with a variety of compounds against different pathogens (Cao et al., ; Lister, ; Papich, ).…”

“…However, these indicators may not be the most suitable for predicting the emergence of resistant mutants in a bacterial population. The mutant prevention concentration (MPC) indicates the susceptibility of the first‐step mutant subpopulation (Canut‐Blasco, Aguilar‐Alfaro, Cobo‐Reinoso, Giménez‐Mestre, & Rodríguez‐Gascón, ; Cao et al., ; Ferran, Dupouy, Toutain, & Bousquet‐Mélou, ; Homma, Hori, Sugimori, & Yamano, ; Wetzstein, ). Evidence suggests that MPC‐based PK/PD parameters correlate better with prevention of bacterial resistance than MIC‐based parameters (Canut‐Blasco et al., ; Cao et al., ; Ferran et al., ; Firsov et al., ; Homma et al., ; Körber‐Irrgang et al., ; Liang et al., ).…”