Effects of danofloxacin dosing regimen on gastrointestinal pharmacokinetics and fecal microbiome in steers.

Effects of danofloxacin dosing regimen on gastrointestinal pharmacokinetics and fecal microbiome in steers.
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DOI:
10.1038/s41598-021-90647-z
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发表时间:
2021-05-27
期刊:
影响因子:
4.6
通讯作者:
Foster DM
Foster DM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Halleran JL;Callahan BJ;Jacob ME;Sylvester HJ;Prange T;Papich MG;Foster DM

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氟喹诺酮类药物是人类医学中常用的一类抗菌剂,世界卫生组织认为至关重要。尽管如此,仍有两种制剂被批准用于治疗肉牛呼吸道疾病。本研究的目的是确定牛接受达氟沙星(一种常用的兽药合成氟喹诺酮类药物)两种给药方案(高剂量:40 mg/kg SC一次或低剂量:20 mg/kg IM q48 hr)之一时的胃肠道药代动力学和对肠道细菌的影响。将达氟沙星以两种不同的给药方案给予12头装有肠超滤装置的阉牛(7月龄),以评估胃肠道药代动力学、胃肠道微生物组的变化和耐药细菌分离株的发展。我们的研究结果表明,两个剂量组的达氟沙星的肠道渗透性高,以及E.在38天期间的选定时间点,给药组之间的大肠杆菌和肠球菌。达氟沙星治疗一致导致广古菌门随时间减少,特别是由于甲烷短杆菌减少。尽管给药组之间的微生物组差异较小,但低剂量组具有较高数量的分离株,其MIC值高到足以引起临床相关耐药性。这些信息将有助于指导兽医制定适当的给药方案,以最大限度地减少抗菌素耐药性的传播。
Fluoroquinolones are a class of antimicrobial commonly used in human medicine, and deemed critical by the World Health Organization. Nonetheless, two formulations are approved for the treatment of respiratory disease in beef cattle. The objective of this study was to determine the gastrointestinal pharmacokinetics and impact on enteric bacteria of cattle when receiving one of the two dosing regimens (high: 40 mg/kg SC once or low: 20 mg/kg IM q48hr) of danofloxacin, a commonly utilized synthetic fluoroquinolone in veterinary medicine. Danofloxacin was administered to 12 steers (age 7 months) fitted with intestinal ultrafiltration devices at two different dosing regimens to assess the gastrointestinal pharmacokinetics, the shifts in the gastrointestinal microbiome and the development of resistant bacterial isolates. Our results demonstrated high intestinal penetration of danofloxacin for both dosing groups, as well as, significant differences in MIC values for E. coli and Enterococcus between dosing groups at selected time points over a 38 day period. Danofloxacin treatment consistently resulted in the Euryarchaeota phyla decreasing over time, specifically due to a decrease in Methanobrevibacter. Although microbiome differences were minor between dosing groups, the low dose group had a higher number of isolates with MIC values high enough to cause clinically relevant resistance. This information would help guide veterinarians as to appropriate dosing schemes to minimize the spread of antimicrobial resistance.
DOI: 10.1038/nmeth.3869
发表时间: 2016-07
期刊: Nature methods
影响因子: 48
作者:
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DOI: 10.1371/journal.pone.0223378
发表时间: 2019-10-04
期刊: PLOS ONE
影响因子: 3.7
作者:
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发表时间: 2013-11-01
影响因子: 10.8
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发表时间: 2007-12
影响因子: 10.4
作者:
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