Antimicrobial Resistance in <i>Escherichia coli</i> Recovered from Feedlot Cattle and Associations with Antimicrobial Use

The objectives of this study were to estimate the prevalence of antimicrobial resistance (AMR) and to investigate the associations between exposures to antimicrobial drugs (AMDs) and AMR in fecal non-type specific Escherichia coli (NTSEC) recovered from a large population of feedlot cattle. Two-stage random sampling was used to select individually identified cattle for enrollment, which were sampled at arrival and then a second time later in the feeding period. Advanced regression techniques were used to estimate resistance prevalences, and to investigate associations between AMD exposures in enrolled cattle and penmates and AMR identified in NTSEC recovered from the second sample set. Resistance was most commonly detected to tetracycline, streptomycin, and sulfisoxazole, and was rarely identified for critically important AMDs. All cattle were exposed to AMDs in feed, and 45% were treated parenterally. While resistance prevalence generally increased during the feeding period, most AMD exposures were not significantly associated with AMR outcomes. Exposures of enrolled cattle to tetracycline were associated with increased resistance to tetracycline and trimethoprim sulfa, while beta-lactam exposures were associated with decreased likelihood of detecting streptomycin resistance. Pen-level AMD exposure measures were not associated with resistance outcomes. These findings suggest that tetracycline treatment of feedlot cattle can be associated with modest increases in risk for recovery of resistant NTSEC, but the numerous treatments with an advanced macrolide (tulathromycin) were not associated with detectable increases in resistance in NTSEC. All cattle were exposed to in-feed treatments of tetracycline and this could limit the ability to identify the full impact of these exposures, but these exposures varied for enrolled cattle varied, providing an opportunity to evaluate a dose response. While AMD exposures were not associated with detectably increased risks for resistance to critically important AMDs, rare resistance outcomes and infrequent exposure to other important AMDs (e.g., cephalosporins) limited our ability to rigorously investigate questions regarding factors that can influence resistance to these important AMDs.

本研究旨在评估抗菌药物耐药性（antimicrobial resistance, AMR）的流行率，并探究从大规模育肥场肉牛群体粪便样本中分离得到的非分型大肠埃希菌（non-type specific Escherichia coli, NTSEC）的抗菌药物（antimicrobial drugs, AMDs）暴露与AMR之间的关联。研究采用两阶段随机抽样法选取个体标识明确的肉牛纳入试验，分别在入栏时及饲养周期后期进行两次采样，通过先进的回归分析技术估算耐药流行率，并分析纳入试验肉牛及其同栏牛的抗菌药物暴露与第二次采样分离得到的NTSEC中检测到的AMR之间的关联。本研究中，四环素、链霉素及磺胺异噁唑的耐药性检出最为常见，而对极重要抗菌药物的耐药性检出率极低。所有肉牛均通过饲料暴露于抗菌药物，其中45%接受了注射给药。尽管饲养周期内耐药流行率整体呈上升趋势，但多数抗菌药物暴露与AMR结局无显著关联。纳入试验的肉牛暴露于四环素时，其对四环素及甲氧苄啶-磺胺类的耐药性会显著升高；而β-内酰胺类（beta-lactam）药物暴露则与链霉素耐药性的检出概率降低相关。同栏水平的抗菌药物暴露指标与耐药结局无显著关联。本研究结果表明，育肥场肉牛的四环素治疗可能会使耐药NTSEC的分离风险小幅升高，但多次使用新型大环内酯类药物托拉菌素（tulathromycin）并未与NTSEC耐药性的可检测升高相关。所有肉牛均接受了饲料添加的四环素治疗，这可能限制了我们全面评估此类暴露影响的能力，但纳入试验肉牛的此类暴露程度存在差异，为评估剂量反应关系提供了可行条件。尽管抗菌药物暴露与极重要抗菌药物耐药性的可检测升高风险无关联，但针对头孢菌素类（cephalosporins）等重要抗菌药物的耐药性检出率较低，且对其他重要抗菌药物的暴露也不频繁，这限制了我们严谨探究影响此类重要抗菌药物耐药性相关因素的能力。