Pharmacokinetic-pharmacodynamic modeling of tylosin against Streptococcus suis in pigs

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.

Evaluating a tylosin dosage regimen for treatment of Staphylococcus delphini infection in mink (Neovison vison): a pharmacokinetic-pharmacodynamic approach

“…azithromycin) the ƒAUC/MIC is an appropriate predictor of effect and can be used as PKPD index [ 6 , 13 , 33 , 34 ]. The selection of f AUC/MIC as PKPD index in this study was based on AIC reduction (Table 3 ) and was in agreement with previous studies on TYL in pig [ 35 ] and duck [ 26 ]. In our simulations for predicting a PKPD target, we selected 30 CFU/mL as a lower limit where no bacterial re-growth would be possible to capture all the curves of bacterial evolution, although for a non-immunocompromised subject, the natural process of bacterial eradication by the immune system can be efficient up to 10 5 CFU/mL [ 36 ].…”

Tissue Residues and Pharmacokinetic/Pharmacodynamic Modeling of Tiamulin Against Mycoplasma anatis in Ducks

“…The value of the area under the concentration-time profile over 24 h (AUC 24h ) for the ex vivo time killing curve was computed by multiplying each tiamulin concentration measured after the oral administration at 60 mg/kg by 24 h (incubation period). Subsequently, the AUC 24h value was divided by the MIC to estimate the AUC 24h /MIC (33)(34)(35).…”

Streptococcus suis serotype 2 enolase interaction with host brain microvascular endothelial cells and RPSA-induced apoptosis lead to loss of BBB integrity

“…SS2 strains JZLQ022 (our collection) and CVCC606 (purchased from the China Veterinary Culture Collection Center [ 24 ]) were isolated from brain material from porcine meningitis cases. Strains were grown on tryptic soy agar (TSA) plates with 5% newborn bovine serum for 10 h at 37 °C.…”