Abstract
BackgroundThe aim of this study was to optimize the dosage regimen of tylosin against S.suis in Pigs using pharmacokinetic-pharmacodynamic (PK-PD) modeling. The antibacterial activity of tylosin against S.suis CVCC606 was investigated in Mueller Hinton (MH) broth and serum. The objectives of this investigation were to study the PD data of tylosin against S.suis CVCC606 and the PK data of tylosin in healthy and diseased model of pigs and formulate a rational dosage regimen for the treatment of pig streptococcosis.ResultsThe minimum inhibitory concentrations (MIC) were 0.25 μg/mL, and the minimal bactericidal concentrations (MBC) were 1 μg/mL in MH broth and serum. The killing curve showed time-dependent activity and weak concentration-dependent antibacterial activity. A pig pneumoniae model of S. suis infection was built by inoculating subcutaneously with S. suis CVCC606. Tylosin was (10 mg/kg b.w) administered intramuscularly (IM) to the healthy and S.suis infected pigs, The pharmacokinetic properties, including area under the curve(AUC), peak concentration (Cmax) and time to reach Cmax (Tmax), were determined in plasma using UV-HPLC method. The AUC, Cmax and Tmax in plasma of healthy and infected pigs were 10.80 ± 2.20 and 10.30 ± 3.46 μg.h/mL, 2.06 ± 0.43 and 2.37 ± 0.38 μg/mL, 1.95 ± 0.22 and 1.58 ± 0.49 h, respectively.ConclusionsThe in vivo PK and in vitro PD data were integrated to determine the surrogate marker of antibacterial activity, Cmax/MIC, AUC/MIC and T>MICwere 8.90, 43.21, 8.86 for healthy pigs, and 9.76, 41.18, 7.56 for infected pigs, respectively. Ex vivo AUC/MIC data were integrated with ex vivo bacterial count to calculate the values for bacteriostatic and bactericidal action, which were 10.67 h and 49.66 h for healthy pigs, 11.73 h and 43.03 h for pigs infected with S.suis. A dosage regimen of 5.32–19.50 mg/kg b.w. every 24 h should be sufficient for tylosin against S.suis.
Highlights
The aim of this study was to optimize the dosage regimen of tylosin against S.suis in Pigs using pharmacokinetic-pharmacodynamic (PK-PD) modeling
Pharmacodynamics minimum inhibitory concentrations (MIC), minimal bactericidal concentrations (MBC) and mutant prevention concentration (MPC) of tylosin against S. suis CVCC606 The MIC values of tylosin against the strain of S. suis CVCC606 were 0.25 μg/mL, and MBC values are 1 μg/ mL in MHB and serum obtained from pigs
Time-kill curve The time-dependent feature of tylosin against S. suis was demonstrated according to the killing profiles (Fig. 1), the increasing rate of killing was observed by increasing the time that S. suis was exposed to tylosin, the killing profiles showed a weak concentration-dependent
Summary
The aim of this study was to optimize the dosage regimen of tylosin against S.suis in Pigs using pharmacokinetic-pharmacodynamic (PK-PD) modeling. The antibacterial activity of tylosin against S.suis CVCC606 was investigated in Mueller Hinton (MH) broth and serum. The objectives of this investigation were to study the PD data of tylosin against S.suis CVCC606 and the PK data of tylosin in healthy and diseased model of pigs and formulate a rational dosage regimen for the treatment of pig streptococcosis. Due to its bacteriostatic action against Gram-positive bacteria, anaerobic bacteria and Mycoplasmas [11], tylosin has been widely used to treat pneumonia, arthritis, respiratory tract infections, porcine streptococcosis and other infections in veterinary medicine [12, 13]. There are limited data available on the Pharmacokinetics/pharmacodynamics model of tylosin in pigs [19]
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