CREATE a PATH: Prevalence at Teaching Hospitals of CRE in Veterinary Patients through Passive Surveillance

由耐碳青霉烯肠杆菌(CRE)引起的人类感染的增加被认为是 疾病控制和预防中心对现代医疗保健最紧迫的威胁之一。直到最近 CRE与医疗保健相关感染(HCAI)有关，但有报道称， 社区现在是一个令人担忧的问题。与此同时，兽医界对有关 从伴生动物中分离出Cre。伴侣动物可能在CRE的传播中发挥作用 在社区中；然而，目前尚不清楚在动物中携带CRE的流行率是多少 美国。本研究的目的是(1)评估耐碳青霉烯类肠杆菌(CRE)的流行情况。 在美国兽医教学医院提供的狗和猫中，(2)鉴定了 通过全基因组测序(WGS)从伴生动物中提取Cre。为了这个项目的第一个目标，现有的 将利用VET-LIRN基础设施来完成短期、概念验证、被动监视项目 用于同伴动物的CRE。与兽医教学医院有关联的总共五个实验室将 参与这项初步研究。所有实验室将使用显色琼脂来筛选30-50个粪便 每月样本超过10个月的CRE。推定为阳性的分离物将被送往加州大学 宾夕法尼亚州实验室用于鉴定、药敏试验(AST)和表型 碳青霉烯酶产酶特性的研究。估计的流行率将计算为 阳性标本占检测样本总数的比例。在第二个目标下， 确认的CRE将被送往路易斯安那州的动物疾病诊断实验室(LADDL) 美国州立大学进行全基因组测序。原始测序数据将通过上载和处理 NCBI病原体检测管道检测耐药基因并通过以下方式鉴定分离株 多位点序列分型及补充分析。基于之前的研究，我们估计 狗和猫的患病率约为1%，这些狗和猫具有不同的遗传背景和不同的品种 碳青霉烯类耐药的不同机制。这项研究将作为更广泛监测的基础 伙伴动物CRE的战略，并将在Vet-LIRN计划内建立能力，以识别和 描述CRE的特征。

The rise of human infections caused by carbapenem-resistant Enterobacterales (CRE) is considered one of the most urgent threats to modern healthcare by the Centers for Disease Control and Prevention. Until recently CRE were associated with healthcare-associated infections (HCAIs) but reports of infections acquired in the community are now a concern. In parallel, there is growing concern in veterinary medicine over reports of the isolation of CRE from companion animals. Companion animals could potentially play a role in CRE transmission in communities; however, it is currently unknown what the prevalence of CRE carriage among animals is in the USA. The aims of this study are to (1) estimate the prevalence of carbapenem-resistant Enterobacterales (CRE) among dogs and cats presenting to veterinary teaching hospitals in the USA and (2) characterize isolates of CRE from companion animals by whole genome sequencing (WGS). For the first aim of this project, the existing Vet-LIRN infrastructure will be leveraged to complete a short-term, proof-of-concept, passive surveillance project for CRE in companion animals. A total of five laboratories associated with veterinary teaching hospitals will participate in this initial study. All laboratories will use chromogenic agar to screen between 30-50 fecal specimens monthly for CRE over 10 months. Presumptive positive isolates will be sent to the University of Pennsylvania’s laboratory for identification, antimicrobial susceptibility testing (AST) and phenotypic characterization of carbapenemase enzyme production. The estimated prevalence will be calculated as the proportion of the positive specimens out of the total number of specimens tested. Under the second aim, confirmed CRE will be sent to the Louisiana Animal Disease Diagnostic Laboratory (LADDL) at the Louisiana State University for whole genome sequencing. Raw sequencing data will be uploaded and processed through the NCBI Pathogen Detection pipeline to detect antimicrobial resistance genes and to characterize isolates by multilocus sequence typing along with supplementary analyses. Based on previous studies, we estimate a prevalence of about 1% among dogs and cats that will have genetically distinct background and harbor a variety of different mechanisms for carbapenem resistance. This study will serve as a basis for wider surveillance strategies for CRE in companion animals and will build capacity within the Vet-LIRN program to identify and characterize CRE.