Transmission Dynamics of Antimocrobial-resistant bacteria in dialysis units

描述（由申请人提供）：感染是慢性血液透析（CHD）患者死亡的第二大常见原因。抗生素耐药细菌（ARB）引起的疾病死亡率高达5倍。冠心病患者ARB发生率持续上升，与该人群中1/3的感染有关。迫切需要新的控制策略，旨在减少ARB获取并最终减少ARB感染。本提案的目标是描述门诊血液透析环境中ARB传播的独特方面，以便开发现有或新的控制策略的创新，有效和实际应用。对包括SARS和艾滋病毒在内的传染原进行的人口水平分析表明，被称为“超级传播者”的一个子群体负责大多数疾病的传播，并且着重于这一个子群体的控制努力是非常有效的。我们的初步数据表明，在门诊的冠心病患者中有一个亚组具有超级传播者的特征。与目前的干预措施相比，针对这一群体的干预措施在预防ARB获取方面可能具有更大的效果。这个多学科的试点应用将结合临床、分子基因分型和数学建模技术，这些技术已经被我们的团队成功地应用于透析单位中ARB的传播动力学特征。在目标1中，我们计划将正在进行的单单位试点研究扩展为多中心前瞻性队列研究，以在个体水平上表征ARB超传播者群体。在目标2中，使用数学模型进行种群水平分析，将描述和量化超级传播者对ARB传播的贡献以及针对该亚群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人层面数据的基础上，并将描述导致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到的。研究小组由一名传染病流行病学家，一名在ARB建模方面具有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有助于制定和实施针对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引起的感染并改善冠心病患者的预后。

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.