Ceftiofur use in cattle: a public health concern?

说明(申请人提供)：本提案的总体目标是确定食用动物中抗生素的使用与人类种群中存在耐药沙门氏菌之间是否存在联系。假设头孢硫呋钠在食用动物中的治疗用途是为了选择肠杆菌科成员对头孢菌素类药物的耐药性。因此，我们的短期目标是确定头孢硫呋钠在患病牛身上的使用是否导致人畜共患沙门氏菌耐药。我们的目的是调查在我们的国家兽医诊断实验室培养的头孢硫氟/头孢曲松耐药分离株的来源，并确定它们是否与佐治亚州公共卫生服务和疾病控制中心确认的人类沙门氏菌病头孢曲松耐药病例有关。 具体目的1.确定我们诊断实验室鉴定的头孢曲松耐药沙门氏菌分离株是否与暴发或散发性沙门氏菌病相关的人类分离株有遗传关系。工作假说将通过PFGE确定农场和人类病例中对头孢曲松耐药的沙门氏菌的遗传相关性，并使用分子技术表征头孢菌素酶基因座来验证。 具体目的2.确定食品生产动物的正常革兰氏阴性菌中头孢硫呋耐药性的流行情况，以及头孢曲松耐药性从动物微生物区系向头孢硫呋沙门氏菌的潜在传播可能通过丰富含有超广谱头孢菌素酶的正常菌群来扩大基因库。工作假说将通过对动物微生物群中的头孢菌素酶(S)的分子分析来验证，这些微生物群来自有或没有头孢硫呋钠使用史的农场。我们还将探讨沙门氏菌对头孢曲松耐药的质粒在动物体外和模拟动物生产环境中传播的可能性。通过对农场动物的调查，我们将了解农场使用抗生素是否会影响沙门氏菌与牛的居住微生物群相互作用而获得抗药性。这项建议旨在让本科生参与分子流行病学调查，以增加他们对生物医学研究的接触。

DESCRIPTION (provided by applicant): The overall objective, of this proposal, is to determine if there is a link between the use of antibiotics in food animals and the presence of resistant Salmonella in the human population. The hypothesis is that the therapeutic use of ceftiofur in food animals is selecting for resistance to cephalosporins in members of the Family Enterobacteriaceae. Therefore, our short-term goal is to determine if the use of ceftiofur in sick cattle has resulted in resistant zoonotic salmonellosis in people. Our intention is to investigate the source of ceftiofur/ceftriaxone-resistant isolates cultured in our State Veterinary Diagnostic Laboratory and determine if they are related to ceftriaxone resistant cases of salmonellosis in humans identified by the Public Health Service in Georgia and the Centers for Disease Control. Specific aim 1. Determine whether ceftriaxone-resistant Salmonella isolates identified by our diagnostic laboratory are genetically related to human isolates associated with outbreak or sporadic cases of salmonellosis. The working hypothesis will be tested by determining the genetic relatedness of ceftriaxone-resistant Salmonella from farms and human cases by PFGE and characterizing the cephalosporinase locus using molecular techniques. Specific aim 2. Determine the prevalence of ceftiofur resistance in the normal, gram negative flora of food production animals and potential transmission of ceftriaxone resistance from animal microflora to Salmonella Ceftiofur usage may amplify the gene reservoir by enriching for normal flora containing extended-spectrum cephalosporinases. The working hypothesis will be tested through molecular analysis of cephalosporinase(s) within animal microflora gathered from farms with or without a history of ceftiofur usage. We will also address the potential for plasmid transmission of ceftriaxone resistance to Salmonella from the animals' microflora in vitro as well as with a simulated animal production environment. By surveying the animals on the farm, we will discern whether antibiotic use on the farm influences the acquisition of drug resistance by Salmonella interacting with the resident microflora of cattle. This proposal seeks to involve undergraduate students in molecular epidemiology investigations to increase their exposure to biomedical research.