title: The Epidemiologic and Pharmacodynamic Cutoff Values of Tilmicosin against Haemophilus parasuis.
abstract: The aim of this study was to establish antimicrobial susceptibility breakpoints for tilmicosin against Haemophilus parasuis, which is an important pathogen of respiratory tract infections. The minimum inhibitory concentrations (MICs) of 103 H. parasuis isolates were determined by the agar dilution method. The wild type (WT) distribution and epidemiologic cutoff value (ECV) were evaluated by statistical analysis. The new bronchoaveolar lavage was used to establish intrapulmonary pharmacokinetic (PK) model in swine. The pharmacokinetic (PK) parameters of tilmicosin, both in pulmonary epithelial lining fluid (PELF) and in plasma, were determined using high performance liquid chromatography method and WinNonlin software. The pharmacodynamic cutoff (COPD) was calculated using Monte Carlo simulation. Our results showed that 100% of WT isolates were covered when the ECV was set at 16 μg/mL. The tilmicosin had concentration-dependent activity against H. parasuis. The PK data indicated that tilmicosin concentrations in PELF was rapidly increased to high levels at 4 h and kept stable until 48 h after drug administration, while the tilmicosin concentration in plasma reached maximum levels at 4 h and continued to decrease during 4-72 h. Using Monte Carlo simulation, COPD was defined as 1 μg/mL. Conclusively, the ECV and COPD of tilmicosin against H. parasuis were established for the first time based on the MIC distribution and PK-PD analysis in the target tissue, respectively. These values are of great importance for detection of tilmicosin-resistant H. parasuis and for effective treatment of clinical intrapulmonary infection caused by H. parasuis.
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University Wuhan, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University Wuhan, China.
authors.forename: Haihong
authors.initials: H
authors.lastname: Hao
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University Wuhan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University Wuhan, China.
authors.forename: Ijaz
authors.initials: I
authors.lastname: Ahmad
authors.affiliation: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University Wuhan, China.
authors.forename: Guyue
authors.initials: G
authors.lastname: Cheng
authors.affiliation: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University Wuhan, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Chen
authors.affiliation: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University Wuhan, China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Tao
authors.affiliation: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University Wuhan, China.
authors.forename: Lingli
authors.initials: L
authors.lastname: Huang
authors.affiliation: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University Wuhan, China.
authors.forename: Yulian
authors.initials: Y
authors.lastname: Wang
authors.affiliation: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University Wuhan, China.
authors.forename: Menghong
authors.initials: M
authors.lastname: Dai
authors.affiliation: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural UniversityWuhan, China; Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Huazhong Agricultural UniversityWuhan, China.
authors.forename: Zhenli
authors.initials: Z
authors.lastname: Liu
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural UniversityWuhan, China; MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural UniversityWuhan, China; Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Huazhong Agricultural UniversityWuhan, China.
authors.forename: Zonghui
authors.initials: Z
authors.lastname: Yuan
keywords: H. parasuis; bronchoaveolar lavage; epidemiologic cutoff value; pharmacodynamic cutoff; tilmicosin