Pharmacokinetic-pharmacodynamic modeling of tylosin against Streptococcus suis in pigs

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 0.25g/mL, and the minimal bactericidal concentrations (MBC) were 1g/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 (10mg/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 (C-max) and time to reach C-max (T-max), were determined in plasma using UV-HPLC method. The AUC, C-max and T-max in plasma of healthy and infected pigs were 10.802.20 and 10.30 +/- 3.46g.h/mL, 2.06 +/- 0.43 and 2.37 +/- 0.38g/mL, 1.95 +/- 0.22 and 1.58 +/- 0.49h, respectively.Conclusions p id=Par3 The in vivo PK and in vitro PD data were integrated to determine the surrogate marker of antibacterial activity, C-max/MIC, AUC/MIC and T(>MIC)were 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 10.67h and 49.66h for healthy pigs, 11.73h and 43.03h for pigs infected with S.suis. A dosage regimen of 5.32-19.50mg/kg b.w. every 24h should be sufficient for tylosin against S.suis.