title: Response of a clinical Escherichia coli strain to repeated cefquinome exposure in a piglet tissue-cage model.
abstract: BACKGROUND
  In order to provide some basis for effective dosage regimens that optimize efficacy with respect to bacteriological and clinical cures, the in vivo activity of cefquinome against a clinical Escherichia coli (E.coli) strain (the minimum inhibitory concentration value for this strain equals to the MIC90 value of 0.25 μg/ml for 210 E.coli strains isolated from pigs) was investigated by using a piglet tissue-cage infection model. The aim was to elucidate the pharmacokinetic/pharmacodynamics (PK/PD) index associated with cefquinome efficacy, and then to identify the magnitude of the PK/PD parameter required for different degree of efficacy in clinical treatment.
  
  
  RESULTS
  Tissue-cage infection model was established in piglets, and then the animals received intramuscular injection of cefquinome twice a day for 3 days to create a range of different drug exposures. The tissue-cage fluid was collected at 1, 3, 6, 9 and 12 h after every drug administration for drug concentrationdetermination and bacteria counting. Different cefquinome regimens produced different percentages of time during that drug concentrations exceeded the MIC (%T > MIC), ranging from 0% to 100%. Cefquinome administration at 0.2, 0.4, 0.6, 0.8, 1, 2 and 4 mg/kg reduced the bacterial count (log10 CFU/mL) in tissue-cage fluid by -1.00 ± 0.32, -1.83 ± 0.08, -2.33 ± 0.04, -2.96 ± 0.16, -2.99 ± 0.16, -2.93 ± 0.11, -3.43 ± 0.18, respectively. The correlation coefficient of the PK/PD index with antibacterial effect of the drug was 0.90 for %T > MIC, 0.62 for AUC0-12/MIC, and 0.61 for Cmax/MIC, suggesting the most important PK/PD parameter was %T > MIC. A inhibitory form of sigmoid maximum effect (Emax) model was used to estimate %T > MIC, and the respective values required for continuous 1/6-log drop, 1/3-log drop and 1/2-log drop of the clinical E.coli count during each 12 h treatment period were 3.97%, 17.08% and 52.68%.
  
  
  CONCLUSIONS
  The data derived from this study showed that cefquinome exhibited time-dependent killing profile. And from the results of the present study, it can be assumed that when %T > MIC reached 52.68%, cefquinome could be expected to be effective against a clinical E.coli strain for which the MIC value is below 0.128 μg/ml (3-log drop of bacteria count can be achieved after six successive administrations for 3 days).
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. 710942824@qq.com.
authors.forename: Mengxiao
authors.initials: M
authors.lastname: Gu
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. 814509278@qq.com.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. 1216591415@qq.com.
authors.forename: Longfei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. 963095077@qq.com.
authors.forename: Mingpeng
authors.initials: M
authors.lastname: Xiong
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. 1083856733@qq.com.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. 2418798401@qq.com.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Gu
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. shenxg@scau.edu.cn.
authors.forename: Xiangguang
authors.initials: X
authors.lastname: Shen
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. hzding@scau.edu.cn.
authors.forename: Huanzhong
authors.initials: H
authors.lastname: Ding
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002511:Cephalosporins / Q000008:administration & dosage / Q000627:therapeutic use*; D015194:Diffusion Chambers, Culture / Q000662:veterinary; D004305:Dose-Response Relationship, Drug; D004927:Escherichia coli Infections / Q000188:drug therapy*; D008297:Male; D008826:Microbial Sensitivity Tests; D011897:Random Allocation; D013552:Swine; D013553:Swine Diseases / Q000382:microbiology*
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C068212:cefquinome