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在小鼠中进行恩诺沙星的治疗性给药不会导致空肠弯曲菌对氟喹诺酮产生耐药性。

Therapeutic administration of enrofloxacin in mice does not select for fluoroquinolone resistance in Campylobacter jejuni.

作者信息

Inglis G Douglas, Zaytsoff Sarah J M, Selinger L Brent, Taboada Eduardo N, Uwiera Richard R E

机构信息

a Agriculture and Agri-Food Canada, 5403-1st Avenue S, Lethbridge, AB T1J 4B1, Canada.

b Department of Agricultural, Food and Nutritional Science, 410 Agriculture/Forestry Centre, University of Alberta, Edmonton, AB T6G 2P5, Canada.

出版信息

Can J Microbiol. 2018 Oct;64(10):681-694. doi: 10.1139/cjm-2017-0741. Epub 2018 May 11.

Abstract

Enrofloxacin is registered for therapeutic use in beef cattle to treat bovine respiratory disease in Canada. A murine model was used to experimentally examine the impact of therapeutic administration of enrofloxacin on fluoroquinolone resistance development in Campylobacter jejuni. Administration of enrofloxacin to mice via subcutaneous injection or per os routes resulted in equivalent levels of bioactive enrofloxacin within the intestine, but bioactivity was short-lived (<48 h after cessation). Enrofloxacin administration did not affect densities of total bacteria, Firmicutes, or Bacteroidetes in digesta and had modest impacts on densities of Enterobacteriaceae. All mice inoculated with C. jejuni NCTC 11168 became persistently colonized by the bacterium. Enrofloxacin reduced C. jejuni cell densities within the cecal and colonic digesta for all treatments, and densities shed in feces as a function of antibiotic duration. None of the C. jejuni isolates recovered from mice after administration of enrofloxacin (n = 260) developed resistance to ciprofloxacin regardless of method or duration of administration. Furthermore, only modest shifts in the minimum inhibitory concentration of the isolates by treatment were noted. The study findings indicate that the risk posed by short-term subcutaneous administration of enrofloxacin for the development of fluoroquinolone resistance in mammals is low.

摘要

恩诺沙星在加拿大被注册用于肉牛治疗牛呼吸道疾病。使用小鼠模型来实验性研究恩诺沙星治疗给药对空肠弯曲菌氟喹诺酮耐药性发展的影响。通过皮下注射或口服途径给小鼠施用恩诺沙星,在肠道内产生的生物活性恩诺沙星水平相当,但生物活性持续时间较短(停药后<48小时)。施用恩诺沙星不影响消化物中总细菌、厚壁菌门或拟杆菌门的密度,对肠杆菌科的密度有适度影响。所有接种空肠弯曲菌NCTC 11168的小鼠都被该细菌持续定植。恩诺沙星在所有处理中均降低了盲肠和结肠消化物中的空肠弯曲菌细胞密度,以及作为抗生素给药持续时间函数的粪便中排出的密度。施用恩诺沙星后从小鼠体内分离出的空肠弯曲菌菌株(n = 260),无论给药方法或持续时间如何,均未对环丙沙星产生耐药性。此外,仅观察到处理后分离株的最低抑菌浓度有适度变化。研究结果表明,短期皮下施用恩诺沙星对哺乳动物氟喹诺酮耐药性发展造成的风险较低。

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