Ceftiofur formulation differentially affects the intestinal drug concentration, resistance of fecal Escherichia coli, and the microbiome of steers
Ceftiofur formulation differentially affects the intestinal drug concentration, resistance of fecal Escherichia coli, and the microbiome of steers
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DOI：
10.1371/journal.pone.0223378
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发表时间：
2019-10-04
期刊：
影响因子：
3.7
通讯作者：
Papich, Mark G.
中科院分区：
文献类型：
--
作者：
Foster, Derek M.;Jacob, Megan E.;Papich, Mark G.
胃肠道中的抗菌药物浓度可能会驱动肠道细菌的抗菌药物耐药性。我们的目的是确定头孢噻呋及其代谢产物在接受头孢噻呋游离酸（CCFA）或盐酸头孢噻呋（CHCL）治疗的牛胃肠道中的浓度，确定这些药物对粪便大肠杆菌最低抑菌浓度（MIC）的影响，并评价微生物组的变化。牛接受CCFA（6.6 mg/kg）单次给药或CHCL（2.2 mg/kg）给药，每24小时一次，持续3天。在血浆、回肠、回肠和结肠中测定头孢噻呋及其代谢产物。粪大肠杆菌浓度和MIC。大肠杆菌和粪便微生物群组成进行评估。在CHCL处理的阉牛的所有采样位置，头孢噻呋的最大浓度均较高。可测量的药物在CCFA处理的阉牛的肠道中持续时间更长。E. CCFA治疗后2周，24小时内的大肠杆菌浓度（P = 0.002）持续下降。在CHCL处理的阉牛中，头孢噻呋在大肠杆菌中的平均MIC。CCFA处理的肉牛在48小时达到峰值（平均MIC = 20.45 μ g/ml，95% CI = 10.29-40.63 μ g/ml），在96小时达到峰值（平均MIC = 10.68 μ g/ml，95% CI = 5.47-20.85 μ g/ml）。两组牛的微生物组的变化是由于厚壁菌门的减少和拟杆菌门的增加。CCFA导致肠道药物浓度延长、降低，并与E.大肠杆菌中头孢噻呋的MIC增加。大肠杆菌在特定的时间点，并在粪便微生物群的变化。CHCL在较短的时间内导致较高的肠道药物浓度。对E.大肠埃希菌浓度和微生物组较小，但粪便中头孢噻呋的MIC增加。大肠杆菌的相似性。
Antimicrobial drug concentrations in the gastrointestinal tract likely drive antimicrobial resistance in enteric bacteria. Our objective was to determine the concentration of ceftiofur and its metabolites in the gastrointestinal tract of steers treated with ceftiofur crystalline-free acid (CCFA) or ceftiofur hydrochloride (CHCL), determine the effect of these drugs on the minimum inhibitory concentration (MIC) of fecal Escherichia coli, and evaluate shifts in the microbiome. Steers were administered either a single dose (6.6 mg/kg) of CCFA or 2.2 mg/kg of CHCL every 24 hours for 3 days. Ceftiofur and its metabolites were measured in the plasma, interstitium, ileum and colon. The concentration and MIC of fecal E. coli and the fecal microbiota composition were assessed after treatment. The maximum concentration of ceftiofur was higher in all sampled locations of steers treated with CHCL. Measurable drug persisted longer in the intestine of CCFA-treated steers. There was a significant decrease in E. coli concentration (P = 0.002) within 24 hours that persisted for 2 weeks after CCFA treatment. In CHCL-treated steers, the mean MIC of ceftiofur in E. coli peaked at 48 hours (mean MIC = 20.45 ug/ml, 95% CI = 10.29-40.63 ug/ml), and in CCFA-treated steers, mean MIC peaked at 96 hours (mean MIC = 10.68 ug/ml, 95% CI = 5.47-20.85 ug/ml). Shifts in the microbiome of steers in both groups were due to reductions in Firmicutes and increases in Bacteroidetes. CCFA leads to prolonged, low intestinal drug concentrations, and is associated with decreased E. coli concentration, an increased MIC of ceftiofur in E. coli at specific time points, and shifts in the fecal microbiota. CHCL led to higher intestinal drug concentrations over a shorter duration. Effects on E. coli concentration and the microbiome were smaller in this group, but the increase in the MIC of ceftiofur in fecal E. coli was similar.