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通过牛奶饮食或全身治疗接触抗菌药物会导致犊牛粪便大肠杆菌的抗菌药物耐药性暂时增加。

Exposure to antimicrobials through the milk diet or systemic therapy is associated with a transient increase in antimicrobial resistance in fecal Escherichia coli of dairy calves.

机构信息

Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, Saint Paul 55108.

Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, Saint Paul 55108.

出版信息

J Dairy Sci. 2018 Nov;101(11):10126-10141. doi: 10.3168/jds.2018-14598. Epub 2018 Aug 30.

Abstract

The objective of this prospective cohort study was to describe the relationship between exposure to antimicrobials, through both the milk diet and systemic therapy, and to describe antimicrobial resistance of fecal Escherichia coli in dairy calves pre- and postweaning. A convenience sample of 15 Minnesota dairy farms was chosen, representing 3 equal cohorts of milk diet fed to preweaned calves: medicated milk replacer (MMR), nonmedicated milk replacer (NMR), or pasteurized nonsaleable milk (PNM). Five newborn calves were enrolled on each farm, with fecal samples collected from each calf at 1, 3, 5, and 16 wk of age. After isolation, 3 colonies of E. coli were randomly selected from each sample to determine antimicrobial susceptibility by minimum inhibitory concentration (Sensititer, Thermo Scientific, Waltham, MA) to 8 antimicrobials in 8 classes. The isolate was given an antimicrobial resistance score (ARS) according to the number of antimicrobial classes to which it was resistant. Any isolate resistant to 3 or more antimicrobials was defined as being multidrug resistant (MDR). Relationships between ARS and MDR (dependent variables) and possible explanatory variables were analyzed using mixed multivariable linear and logistic regression models, respectively, with critical P-values adjusted for multiple contrasts. Seventy percent of isolates were resistant to sulfadimethoxine. For wk 1 and 3, the mean ARS values were greatest for fecal E. coli from calves fed MMR or PNM compared with NMR, with no difference in ARS values between the MMR and PNM groups at either time point. At wk 5, the mean ARS value was greatest for fecal E. coli from calves fed MMR (3.56 ± 0.45; mean ± SE), intermediate for calves fed PNM (2.64 ± 0.45), and lowest for calves fed NMR (1.54 ± 0.45). However, by wk 16, the mean ARS values were ≤1.0 and did not differ among milk diets. Evaluation of the proportion of isolates with MDR mirrored the results of the ARS analysis (MDR more prevalent in MMR and PNM groups preweaning; no difference among milk diets at 16 wk). There was a tendency for an increase in ARS at wk 5 (1.28 ± 0.70), and the odds for MDR in fecal E. coli were estimated to be 5.2 (95% confidence interval = 0.67, 35.7) and 101.1 (95% confidence interval = 1.15, >999.9) higher at wk 3 and 5 if the calf was treated with a systemic antimicrobial within the 14-d period before sampling. These findings suggest that exposure to antimicrobials through the milk diet or systemic therapy may result in a transient increase in resistance in fecal E. coli, but once the antimicrobial pressure is removed, susceptible E. coli are able to flourish again, resulting in an overall decrease in resistance.

摘要

本前瞻性队列研究的目的是描述通过牛奶饮食和全身治疗接触抗菌药物与犊牛断奶前和断奶后粪便大肠杆菌的抗菌药物耐药性之间的关系。选择了明尼苏达州的 15 个奶牛场进行了方便抽样,代表了三种不同的牛奶饮食喂养未断奶小牛:含药代乳品(MMR)、不含药代乳品(NMR)或巴氏消毒不合格奶(PNM)。每个农场有 5 头新生小牛被纳入研究,每头小牛在 1、3、5 和 16 周龄时采集粪便样本。分离后,从每个样本中随机选择 3 个大肠杆菌菌落,通过最低抑菌浓度(Sensititer,Thermo Scientific,Waltham,MA)来确定对 8 类 8 种抗菌药物的敏感性。根据对 3 种或更多种抗菌药物的耐药性,将分离株的抗菌药物耐药性评分(ARS)分为相应的类别。任何对 3 种或 3 种以上抗菌药物耐药的分离株被定义为多药耐药(MDR)。使用混合多变量线性和逻辑回归模型分别分析 ARS 和 MDR(因变量)与可能的解释变量之间的关系,并对多个对比进行了临界 P 值调整。70%的分离株对磺胺二甲氧嘧啶有耐药性。在第 1 周和第 3 周,与 NMR 相比,接受 MMR 或 PNM 喂养的小牛粪便中大肠杆菌的平均 ARS 值最高,在这两个时间点,MMR 和 PNM 组之间的 ARS 值没有差异。在第 5 周,接受 MMR 喂养的小牛粪便中大肠杆菌的平均 ARS 值最高(3.56 ± 0.45;均值 ± SE),接受 PNM 喂养的小牛居中(2.64 ± 0.45),接受 NMR 喂养的小牛最低(1.54 ± 0.45)。然而,到第 16 周,平均 ARS 值均≤1.0,并且三种牛奶饮食之间没有差异。对 MDR 分离株比例的评估与 ARS 分析结果一致(断奶前 MMR 和 PNM 组中 MDR 更为普遍;16 周时三种牛奶饮食之间没有差异)。在第 5 周时,ARS 值有升高的趋势(1.28 ± 0.70),如果在采样前 14 天内对小牛进行了全身抗菌药物治疗,粪便大肠杆菌中 MDR 的可能性估计分别增加 5.2 倍(95%置信区间=0.67,35.7)和 101.1 倍(95%置信区间=1.15,>999.9)。这些发现表明,通过牛奶饮食或全身治疗接触抗菌药物可能导致粪便大肠杆菌的耐药性暂时增加,但一旦抗菌压力消除,敏感的大肠杆菌又能够再次繁殖,导致耐药性总体下降。

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