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头孢喹肟在仔猪组织笼模型中对多杀性巴氏杆菌的药代动力学/药效学整合

Pharmacokinetic/pharmacodynamic integration of cefquinome against Pasteurella Multocida in a piglet tissue cage model.

作者信息

Zhang Longfei, Wu Xun, Huang Zilong, Kang Zheng, Chen Yuqin, Shen Xiangguang, Cai Qinren, Ding Huanzhong

机构信息

Guangdong Key Laboratory for Veterinary Drug Development and Safety Evaluation, South China Agricultural University, Guangzhou, China.

Technical Center for Inspection and Quarantine, Zhuhai Entry-Exit Inspection and Quarantine Bureau, Zhuhai, China.

出版信息

J Vet Pharmacol Ther. 2019 Jan;42(1):60-66. doi: 10.1111/jvp.12705. Epub 2018 Nov 8.

Abstract

To explore the in vivo antimicrobial activity of cefquinome against Pasteurella multocida in piglets, a piglet tissue cage infection model was used in this study. After the population of P. multocida reached 10  CFU/mL in a tissue cage, piglets received an intramuscular administration of cefquinome at 0.2, 0.4, 0.8, 1, 2, and 4 mg/kg once daily for 3 days. To assess the tissue cage pharmacokinetics (PKTCF) of cefquinome, tissue cage fluid was collected for cefquinome analysis at 1, 3, 6, 9, 12, and 24 hr after each of the 3 daily drug administrations. Bacteria were counted every 24 hr after drug administration and at 48 and 72 hr after the last administration. Evaluation of the relationship between pharmacokinetic/pharmacodynamic (PK/PD) parameters and the antibacterial effect showed that the surrogate of %T > minimum inhibitory concentration (MIC) (R  = 0.981) was the best PK/PD index that correlated with effectiveness of cefquinome against P. multocida. The respective values of %T > MIC required for continuous 1/3-log, 1/2-log, and 1-log reductions were 14.23, 34.45, and 73.44%, respectively, during each 24-hr treatment period. In conclusion, cefquinome exhibited a potent antibacterial effect against P. multocida. When %T > MIC reached 73.44%, cefquinome exhibited a bactericidal effect against P. multocida after three successive daily administrations.

摘要

为了探究头孢喹肟对仔猪多杀性巴氏杆菌的体内抗菌活性,本研究采用了仔猪组织笼感染模型。当组织笼内多杀性巴氏杆菌数量达到10⁷ CFU/mL后,仔猪每天一次肌肉注射0.2、0.4、0.8、1、2和4 mg/kg的头孢喹肟,持续3天。为了评估头孢喹肟的组织笼药代动力学(PKTCF),在每日3次给药后的第1、3、6、9、12和24小时收集组织笼液进行头孢喹肟分析。给药后每24小时以及最后一次给药后的48和72小时进行细菌计数。药代动力学/药效学(PK/PD)参数与抗菌效果之间的关系评估表明,%T>最低抑菌浓度(MIC)的替代指标(R² = 0.981)是与头孢喹肟对多杀性巴氏杆菌有效性相关的最佳PK/PD指数。在每个24小时治疗期间,持续1/3对数、1/2对数和1对数降低所需的%T>MIC值分别为14.23%、34.45%和73.44%。总之,头孢喹肟对多杀性巴氏杆菌表现出强大的抗菌作用。当%T>MIC达到73.44%时,连续每日给药3次后,头孢喹肟对多杀性巴氏杆菌表现出杀菌作用。

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