Pharmacokinetics of enrofloxacin and ceftiofur in plasma, interstitial fluid, and gastrointestinal tract of calves after subcutaneous injection, and bactericidal impacts on representative enteric bacteria
Pharmacokinetics of enrofloxacin and ceftiofur in plasma, interstitial fluid, and gastrointestinal tract of calves after subcutaneous injection, and bactericidal impacts on representative enteric bacteria
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DOI：
10.1111/jvp.12236
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发表时间：
2016-02-01
影响因子：
1.3
通讯作者：
Papich, M. G.
中科院分区：
文献类型：
--
作者：
Foster, D. M.;Jacob, M. E.;Papich, M. G.
本研究的目的是确定牛皮下注射恩诺沙星或头孢硫呋钠后的肠道抗菌药物浓度，以及它们对典型肠道细菌的影响。在12头接受恩诺沙星或头孢硫呋钠治疗的牛的回肠和结肠内植入超滤装置。在给药后48小时内采集样本进行药代动力学/药效学分析。粪肠球菌和肠沙门氏菌(各5×10(5)cfu/m L)在体外暴露于两种药物的峰值浓度和尾浓度(给药后48 h)作用24 h，观察其对MIC的抑制作用和MIC的变化。恩诺沙星在回肠和结肠的组织渗透系数分别为1.6和2.5，而恩诺沙星的活性代谢物环丙沙星的组织渗透系数分别为0.7和1.7。头孢硫呋酯被迅速消除，组织渗透系数分别为0.39和0.25。恩诺沙星各浓度对肠球菌均有杀菌作用，对粪肠球菌有明显的杀菌作用。头孢硫呋峰浓度对肠杆菌有杀菌作用，尾部浓度显著抑制生长。粪肠球菌在所有头孢硫呋钠浓度下均有生长。在研究结束时，接触抗菌剂峰值和尾部浓度的两种微生物的最低抑菌浓度都没有变化。恩诺沙星和头孢硫呋钠达到了能够减少肠道细菌的肠道浓度，但头孢硫呋钠在肠道中的短暂暴露可能会选择耐药微生物。
This study's objectives were to determine intestinal antimicrobial concentrations in calves administered enrofloxacin or ceftiofur sodium subcutaneously, and their impact on representative enteric bacteria. Ultrafiltration devices were implanted in the ileum and colon of 12 steers, which received either enrofloxacin or ceftiofur sodium. Samples were collected over 48 h after drug administration for pharmacokinetic/pharmacodynamic analysis. Enterococcus faecalis or Salmonella enterica (5 x 10(5) CFU/mL of each) were exposed in vitro to peak and tail (48 h postadministration) concentrations of both drugs at each location for 24 h to determine inhibition of growth and change in MIC. Enrofloxacin had tissue penetration factors of 1.6 and 2.5 in the ileum and colon, while ciprofloxacin, an active metabolite of enrofloxacin, was less able to cross into the intestine (tissue penetration factors of 0.7 and 1.7). Ceftiofur was rapidly eliminated leading to tissue penetration factors of 0.39 and 0.25. All concentrations of enrofloxacin were bactericidal for S. enterica and significantly reduced E. faecalis. Peak ceftiofur concentration was bactericidal for S. enterica, and tail concentrations significantly reduced growth. E. faecalis experienced growth at all ceftiofur concentrations. The MICs for both organisms exposed to peak and tail concentrations of antimicrobials were unchanged at the end of the study. Enrofloxacin and ceftiofur achieved intestinal concentrations capable of reducing intestinal bacteria, yet the short exposure of ceftiofur in the intestine may select for resistant organisms.