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.
Highlights
To optimize antimicrobial therapy that maximizes efficacy and minimizes selection of resistance, the pharmacokinetics (PKs) and pharmacodynamics (PDs) characteristics need to be integrated
The main goal of our study was to re-evaluate in vivo antimicrobial activity of marbofloxacin against P. multocida based on major susceptible cell (MIC) and mutant prevention concentration (MPC) in a tissue-cage model in calves
The MICs for the post-treatment isolates recovered from tissue cages did not change 24 h after exposure to marbofloxacin therapy
Summary
To optimize antimicrobial therapy that maximizes efficacy and minimizes selection of resistance, the pharmacokinetics (PKs) and pharmacodynamics (PDs) characteristics need to be integrated. Time-dependent killing is characteristic of β-lactams, macrolides, and clindamycin, and seeks to optimize the duration of exposure of a pathogen to an antimicrobial. Their major PK/PD parameter correlating with effectiveness is the percentage of the dosing interval that the antibiotic. The concentration-dependent killing, such as quinolones and aminoglycosides, seeks to maximize antimicrobial concentration, and their major PK/PD parameter correlating with effectiveness is the ratio of 24 h area under the concentration-time curve or the peak antibiotic concentration divided by major susceptible cell (MIC; AUC24 h/MIC or Cmax/MIC). MPC-based PK/PD indices can be very useful PD parameters for optimization of antimicrobial therapy
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