Transmission Dynamics of Antimocrobial-resistant bacteria in dialysis units

描述（由申请方提供）：感染是需要长期血液透析（CHD）患者的第二大常见死因。由耐药性细菌（ARB）引起的那些与高达5倍的死亡率有关。CHD患者中ARB的发生率持续上升，并与该人群中1/3的感染有关。迫切需要旨在减少ARB获得和最终ARB感染的新控制策略。本提案的目的是描述门诊血液透析环境中ARB传播的独特方面，以开发现有或新型控制策略的创新、有效和实际应用。对包括SARS和艾滋病毒在内的传染源进行的人口一级的分析表明，一个被称为“超级传播者”的亚群对大多数疾病的传播负有责任，而针对这一亚群患者的控制工作非常有效。我们的初步数据表明，有一个亚组的冠心病患者在门诊设置的特点超级传播者。针对该亚组的干预措施可能比目前采取的干预措施对预防ARB获得的影响更大。该多学科试点应用将结合联合收割机临床、分子基因分型和数学建模技术，这些技术已被我们的团队成功应用于表征透析单位中ARB的传播动力学。在目标1中，我们计划将一项正在进行的单单位试点研究扩展为一项多中心前瞻性队列研究，以在个体水平上描述ARB超级传播者组的特征。在目标2中，使用数学模型进行人群水平分析，将描述和量化超级传播者对ARB传播的贡献以及针对该亚组的控制策略的有效性。这些模型将建立在从队列研究中获得的个体水平数据的基础上，并将描述促进ARB传播的众多相互关联的动态因素。这是临床研究无法捕捉的。该研究团队由一名传染病流行病学家、一名具有ARB建模专业知识的数学家以及透析人群感染和ARB领域的领导者组成。从该提案中获得的数据将允许开发和实施针对ARB超级传播者的创新控制策略。限制ARB的传播将最终减少ARB引起的感染并改善CHD患者的结局。

DESCRIPTION (provided by applicant): Infections are the second most common cause of death in patients requiring chronic hemodialysis (CHD). Those caused by antibiotic-resistant bacteria (ARB) are associated with up to 5-fold higher mortality rates. Rates of ARB continue to rise among CHD patients and are implicated in 1/3 of infections in this population. Novel control strategies aimed at decreasing ARB acquisition and ultimately ARB infections are urgently needed. The goal of this proposal is to characterize the unique aspects of ARB transmission in the out- patient hemodialysis setting in order to develop innovative, effective and practical applications of existing or novel control strategies. Population-level analysis of infectious agents, including SARS and HIV, document that a subgroup of individuals, termed the "superspreaders", are responsible for the majority of disease spread, and that control efforts focusing on this subgroup of patients is highly effective. Our preliminary data suggest that there is a subgroup of CHD patients in the out-patient setting characteristic of superspreaders. Focusing interventions to this subgroup may have considerably larger effects on preventing ARB acquisition than interventions currently in place. This multidisciplinary pilot application will combine clinical, molecular genotyping and mathematical modeling techniques that have been successfully applied by our group to characterize the transmission dynamics of ARB in dialysis units. In aim 1, we plan to extend an on-going single-unit pilot study into a multicenter prospective cohort study to characterize the group of superspreaders of ARB at the individual-level. In aim 2, a population-level analysis, using mathematical models, will characterize and quantify the contribution of the superspreaders to ARB spread and the efficacy of control strategies focusing on this subgroup. These models will build on individual-level data obtained from the cohort study and, will characterize the numerous interrelated and dynamic factors contributing to the spread of ARB. which clinical studies cannot capture. The research team is comprised of an infectious disease epidemiologist, a mathematician with expertise in ARB modeling and, a leader in the field of infections and ARB in the dialysis population. The data obtained from this proposal will allow the development and implementation of innovative control strategies targeted at the superspreaders of ARB. Limiting ARB spread will ultimately reduce infections caused by ARB and improve CHD patient outcomes.