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恩诺沙星不同剂量对人工感染鼠伤寒沙门氏菌鸡的临床疗效和耐药性发展的影响。

The effects of different enrofloxacin dosages on clinical efficacy and resistance development in chickens experimentally infected with Salmonella Typhimurium.

机构信息

National Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA Key Laboratory for Detection of Veterinary Drug Residues, Wuhan, China.

MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan, China.

出版信息

Sci Rep. 2017 Sep 15;7(1):11676. doi: 10.1038/s41598-017-12294-7.

Abstract

To investigate the optimal dosage which can improve clinical efficacy and minimize resistance, pharmacokinetics/pharmacodynamics model of enrofloxacin was established. Effect of enrofloxacin treatments on clearance of Salmonella in experimentally infected chickens and simultaneously resistance selection in Salmonella and coliforms were evaluated in three treatment groups (100, PK/PD designed dosage of 4, 0.1 mg/kg b.w.) and a control group. Treatment duration was three rounds of 7-day treatment alternated with 7-day withdrawal. Results showed that 100 mg/kg b.w. of enrofloxacin completely eradicated Salmonella, but resistant coliforms (4.0-60.8%) were selected from the end of the second round's withdrawal period till the end of the experiment (days 28-42). PK/PD based dosage (4 mg/kg b.w.) effectively reduced Salmonella for the first treatment duration. However upon cessation of medication, Salmonella repopulated chickens and persisted till the end with reduced susceptibility (MIC = 0.03-0.25 mg/L). Low frequency (5-9.5%) of resistant coliforms was selected (days 39-42). Enrofloxacin at dosage of 0.1 mg/kg b.w. was not able to eliminate Salmonella and selected coliforms with slight decreased susceptibility (MIC = 0.25 mg/L). In conclusion, short time treatment (7 days) of enrofloxacin at high dosage (100 mg/kg b.w.) could be effective in treating Salmonella infection while minimizing resistance selection in both Salmonella and coliforms.

摘要

为了研究能够提高临床疗效并最小化耐药性的最佳剂量,建立了恩诺沙星的药代动力学/药效学模型。在三个治疗组(100mg/kg bw、PK/PD 设计剂量 4、0.1mg/kg bw)和对照组中,评估了恩诺沙星治疗对实验感染鸡体内沙门氏菌清除率的影响,以及同时对沙门氏菌和大肠菌群的耐药性选择。治疗时间为三轮 7 天治疗,然后停药 7 天。结果表明,100mg/kg bw 的恩诺沙星可完全根除沙门氏菌,但从第二轮停药期结束到实验结束(第 28-42 天),选择出耐药性大肠菌群(4.0-60.8%)。基于 PK/PD 的剂量(4mg/kg bw)可有效减少沙门氏菌的首次治疗时间。然而,停止用药后,沙门氏菌重新在鸡体内繁殖,并一直持续到实验结束,敏感性降低(MIC=0.03-0.25mg/L)。耐药性大肠菌群的选择频率较低(5-9.5%)(第 39-42 天)。0.1mg/kg bw 的恩诺沙星不能根除沙门氏菌,选择出敏感性略有降低的大肠菌群(MIC=0.25mg/L)。结论是,高剂量(100mg/kg bw)短时间(7 天)治疗恩诺沙星可有效治疗沙门氏菌感染,同时最小化沙门氏菌和大肠菌群的耐药性选择。

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