TRANSMISSION DYNAMICS OF MULTI-DRUG RESISTANT UROPATHOGENIC E. coli IN BANGLADESH

 描述(由申请人提供)：多重耐药(MDR)，社区获得性尿路感染(UTI)导致严重的医疗并发症，包括败血症。尤其令人担忧的是，对第三代头孢菌素(3GC)和碳青霉烯类抗生素的耐药性不断上升。在世界上大多数地区，很大比例的社区获得性尿路感染是由属于相关谱系的一组有限的多重耐药大肠杆菌菌株引起的，或者是由致病菌和环境革兰氏阴性菌共享耐药基因的大肠杆菌菌株引起的。研究表明，多药耐药致尿路感染大肠杆菌(UPEC)与引起家禽感染的大肠杆菌具有相同的遗传谱系，表明耐药UPEC可能通过食源性传播。然而，还需要更多的研究来准确量化食用和食用动物作为引起耐药尿路感染的大肠杆菌病原体的宿主所起的作用。我们的项目将研究多药耐药UPEC在孟加拉国达卡的传播动态，作为UPEC克隆谱系及其耐药性决定因素如何在社区传播的范例，而不是在医疗保健环境中传播。我们计划在孟加拉国进行这个项目，因为这个国家和次大陆的其他国家似乎是全球观察到的许多耐多药肠杆菌科生物和谱系的重要储存库。我们将分三个阶段进行这项研究：首先，我们将确定 尿路感染患者中耐多药大肠埃希菌的流行趋势(yr1至yr3.5)，并确定与多药耐药尿路感染相关的危险因素。其次，我们将研究MDR UPEC的零售食品、水和家禽来源(yr1.5-yr3.5)。最后，我们将比较来自UTI和食物来源的分离株的耐药性和基因特征，以追踪与社区获得性UTI相关的UPEC的传播方式(yr2-yr4.5)。将使用共享其遗传谱系的分离株的全基因组测序(基于PFGE和MLST数据)来确定传播方向。该项目总共需要60个月的时间。该项目将使我们能够定量地确定食品和食品生产动物作为大肠杆菌病原体储存库对一种重要和常见的社区获得性感染--尿路感染--的影响。如果这些水库被证明是这些感染的主要来源，我们将能够设计出更有针对性的公共卫生干预措施来预防它们。

 DESCRIPTION (provided by applicant): Multidrug-resistant (MDR), community-acquired urinary tract infections (UTI) contribute to severe medical complications, including sepsis. Of particular concern is the rising resistance against third generation cephalosporins (3GC) and carbapenems. A large proportion of community-acquired UTI in most regions of the world are caused by a limited set of multi-drug resistant E. coli strains belonging to related lineages, or E coli strains that harbor drug resistance genes shared by pathogenic and environmental Gram negative bacteria. Studies have shown that MDR uropathogenic E. coli (UPEC) share the same genetic lineages with E. coli causing infection in poultry, indicating potential foodborne transmissions of antibiotic resistant UPEC. However, additional research is required to accurately quantify the contribution of food and food animals as reservoirs for E. coli pathogens that cause drug-resistant UTI. Our project will examine the transmission dynamics of MDR UPEC in Dhaka, Bangladesh as a paradigm of how UPEC clonal lineages and their drug-resistance determinants disseminate in community as opposed to healthcare settings. We plan to do this project in Bangladesh as this country along with other countries in the sub-continent appear to be an important reservoir of many multidrug-resistant Enterobacteriaceae organisms and lineages that are observed globally. We will do this study in 3 phases: first we will determine the trend in prevalence of MDR E. coli in patients with UTI (yr1 to yr3.5) and identify risk factor associated with MDR UTI. Second, we will study the retail food, water and poultry sources for MDR UPEC (yr1.5-yr3.5). Finally, we will compare the antibiotic resistance profiles and genotypic characteristics of isolates from UTI and food sources to track mode of transmission of UPEC associated with community acquired UTI (yr2-yr4.5). Whole genome sequencing of isolates sharing their genetic lineages (based on PFGE and MLST data) will be used to determine the direction of transmission. Altogether, the project will take 60 months. This project will enable us to quantitatively determine the impact, if any, of food and food-producing animals as reservoirs for E. coli pathogens on an important and common community-acquired infection-UTI. If such reservoirs turn out to be a major source of these infections, we will be able to devise more focused public health interventions to prevent them.