Abstract
The goal of this study was to establish the epidemiological, pharmacodynamic cut-off values, optimal dose regimens for tildipirosin against Haemophilus parasuis. The minimum inhibitory concentrations (MIC) of 164 HPS isolates were determined and SH0165 whose MIC (2 μg/ml ) were selected for PD analysis. The ex vivo MIC in plasma of SH0165 was 0.25 μg/ml which was 8 times lower than that in TSB. The bacteriostatic, bactericidal and elimination activity (AUC24h/MIC) in serum were 26.35, 52.27 and 73.29 h based on the inhibitory sigmoid Emax modeling. The present study demonstrates that 97.9% of the wild-type (WT) isolates were covered when the epidemiological cut-off value (ECV) was set at 8 μg/ml. The parameters including AUC24h, AUC, T1/2, Cmax, CLb and MRT in PELF were 19.56, 60.41, 2.32, 4.02, 56.6, and 2.63 times than those in plasma, respectively. Regarding the Monte Carlo simulation, the COPD was defined as 0.5 μg/ml in vitro, and the optimal doses to achieve bacteriostatic, bactericidal and elimination effect were 1.85, 3.67 and 5.16 mg/kg for 50% target, respectively, and 2.07, 4.17 and 5.78 mg/kg for 90% target, respectively. The results of this study offer a more optimised alternative for clinical use and demonstrated that 4.17 mg/kg of tildipirosin by intramuscular injection could have an effect on bactericidal activity against HPS. These values are of great significance for the effective treatment of HPS infections, but it also be deserved to be validated in clinical practice in the future research.
Highlights
Haemophilus parasuis (HPS) is a Gram-negative bacterium belongs to of the Pasteurella genus
The purpose of the current study was to establish the epidemiological cutoff values (ECVs) and PK/PD cutoff (COPD) of tildipirosin against HPS based on wild-type minimum inhibitory concentrations (MIC) distributions and PK/PD data in vitro and ex vivo, respectively, and compare the pharmacokinetics in plasma and pulmonary epithelial lining fluid (PELF)
The MIC for chloromycetin against Escherichia coli (ATCC25922) was found to be 8 μg/ml, which is within and suitable for the acceptable quality control (QC) range according to the CLSI (M31-A3)
Summary
Haemophilus parasuis (HPS) is a Gram-negative bacterium belongs to of the Pasteurella genus. The HPS bacterium is a common inhabitant of the upper respiratory tract in pigs, and infection is characterised by arthritis, meningitis and polyserositis [1, 2]. HPS can invade the body and cause a systemic infection, and is associated with the transportation, weaning and impaired maternal immunity. According to previous reports More than 15 kinds of HPS serovars had been described. Serovars 1, 5, 10, 12, 13 and 14 have been reported to be highly pathogenic, causing the death or morbidity. Serovars 4 and 5 are the most epidemic among isolates in China [3], and this pathogen has caused a massive worldwide economic losses in the pigs industry in recent decades
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