In vivo evaluation of mutant selection window of cefquinome against Escherichia coli in piglet tissue-cage model

BMC Veterinary Research

Huanzhong Ding¹  Xiangguang Shen¹  Nan Zhang¹  Mengxiao Gu¹  Xiaohong Li¹  Yafei Li¹  Xiaoyan Gu¹  Bingxu Zhang¹ 

[1] National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China

关键词: Piglets;    Cefquinome;    Mutant selection window;    Tissue-cage models;   

Others  :  1091696
DOI  :  10.1186/s12917-014-0297-1

 received in 2014-08-27, accepted in 2014-12-08,  发布年份 2014

【 摘 要 】

Background

The resistance of cephalosporins is significantly serious in veterinary clinic. In order to inhibit the bacterial resistance production, the mutant selection window (MSW) hypothesis with Escherichia coli (E. coli) ATCC 25922 exposed to cefquinome in an animal tissue-cage model was investigated.

Results

Localized infection with E. coli was established in piglets, and the infected animals were administrated intramuscularly with various doses and intervals of cefquinome to provide antibiotic concentrations below the MIC₉₉, between the MIC₉₉ and the mutant prevention concentration (MPC), and above the MPC. E. coli lost susceptibility when drug concentrations fluctuated between the lower and upper boundaries of the window, which defined in vitro as the MIC₉₉ (0.06 μg/mL) and the MPC (0.16 μg/mL) respectively. For PK/PD parameters, there were no mutant selection enrichment when T>MIC₉₉ was ≤ 25% or T>MPC was ≥ 50% of administration interval. When T>MIC₉₉ was > 25% and T>MPC was <50% of administration interval, resistance selection was observed. When AUC_{24 h}/MIC₉₉ and AUC_{24 h}/MPC were considered, the mutant selection window extended from 32.84 h to 125.64 h and from 12.83 h to 49.09 h, respectively.

Conclusions

These findings demonstrate that the MSW exists in vivo for time-dependent antimicrobial agents, and its boundaries fit well with those determined in vitro. Maintenance of antimicrobial concentrations above the MPC for > 50% of administration interval is a straightforward way to restrict the acquisition of resistance in this tissue cage model. This situation was achieved with daily intramuscular doses of 1 mg cefquinome/kg body weight.

【 授权许可】

   
2014 Zhang et al.; licensee BioMed Central.

【 图 表 】

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