Ceftiofur use in cattle: a public health concern?

描述（由申请人提供）：本提案的总体目标是确定在食用动物中使用抗生素与人类中存在耐药性沙门氏菌之间是否存在联系。假设头孢噻呋在食用动物中的治疗用途是选择肠杆菌科成员对头孢菌素的耐药性。因此，我们的短期目标是确定在病牛中使用头孢噻呋是否导致人耐药人畜共患沙门氏菌病。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噻呋/头孢曲松耐药分离株的来源，并确定它们是否与格鲁吉亚公共卫生服务和疾病控制中心确定的人类沙门氏菌病头孢曲松耐药病例相关。 具体目标1.确定由我们的诊断实验室鉴定的头孢曲松耐药沙门氏菌分离株是否与沙门氏菌病暴发或散发病例相关的人类分离株有遗传相关性。通过PFGE确定来自农场和人类病例的头孢曲松耐药沙门氏菌的遗传相关性，并使用分子技术表征头孢菌素酶位点，对工作假设进行检验。 具体目标2。确定头孢噻呋耐药性在食品生产动物的正常革兰氏阴性植物群中的流行率以及头孢曲松耐药性从动物微植物群向沙门氏菌的潜在传播。头孢噻呋的使用可通过富集含有超广谱头孢菌素酶的正常植物群来扩大基因库。将通过从有或无头孢噻呋使用史的农场收集的动物微生物区系中头孢菌素酶的分子分析来检验工作假设。我们还将讨论在体外以及模拟动物生产环境中，从动物微生物菌群中传播头孢曲松耐药性沙门氏菌的质粒的可能性。通过调查农场上的动物，我们将辨别农场上抗生素的使用是否会影响沙门氏菌与牛的常驻微生物群落相互作用而获得耐药性。该提案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.