Sepsis phenotypes at risk for infections caused by multidrug resistant Gram-negative bacilli: elucidating the impact of sepsis definition and patient case mix on prediction performance

项目摘要 脓毒症是一种毁灭性的综合征，是死亡、发病和医疗费用的主要原因。其 抗生素耐药性的上升加剧了这种影响。改善脓毒症结局主要是由于 根据估计的多药耐药性（MDR）风险及时开具抗生素处方。以前的型号 严重高估了MDR风险，加剧了抗生素耐药率和过量耐药率的上升。 mortality.这项K 08研究的总体目标是确定常见的脓毒症表型， 将使更好的处方实践和标准化的比较，在医院，这将有助于 执业临床医生、研究人员、医疗机构和政策制定者。这些主题相互关联 随着NIGMS对寻找创新方法和利用大数据改善败血症的兴趣 成果。我们的三个具体目标反映了这些目标：（1）建立耐药革兰氏耐药阈值， 阴性杆菌（GNB）引起脓毒症，（2）评估脓毒症定义对风险性能的影响 MDR GNB的预测模型，和（3）在良好平衡的模型中鉴定MDR GNB高风险的败血症表型。 队列并评估病例组合对风险预测模型性能的影响。我们将从数学上推导出 将群体耐药率与个体患者在败血症中的死亡风险联系起来的耐药阈值， MDR GNB，评估影响预测性能的因素，并整合来自15家医院的丰富临床数据 在我们的医疗保健系统中，以确定稳定的常见脓毒症表型。Vazquez Guillamet医生接受过 传染病和重症监护医学以及危重患者抗菌素耐药性的经验。 这项建议将建立在她的临床工作和以前的研究经验，在寻找创新的方法， 解决传染病和重症监护医学交叉点的挑战性问题。巴斯克斯医生 Guillamet有六个职业目标：（1）追求临床流行病学的高级培训;（2）获得以下技能： 高级线性回归和多级建模;（3）学习监督机器学习方法;（4）获取 医疗保健大数据管理技能和处理缺失数据的方法;（5）提高科学性 沟通，公关，和领导，（6）参加培训，在负责任的行为， research.她将通过教学课程，实践研究经验，并积极实现这些目标 来自传染病、重症监护医学和应用临床信息学专家的指导。她将 继续开发创新方法，以缓解抗生素耐药性危机，特别是在重症患者中， 成为临床医学和临床应用交叉点的分析翻译 信息学.圣路易斯华盛顿大学肥沃的研究环境， 团队，以及精心设计的职业发展计划将使Vazquez Guillamet博士能够实现她的长期目标 目标是成为独立资助的临床研究人员，利用大数据开发风险应用程序 抗菌素耐药性和脓毒症的预测、监测和结果比较。

PROJECT ABSTRACT Sepsis is a devastating syndrome that represents a leading cause of death, morbidity, and healthcare costs. Its impact is amplified by rising rates of antimicrobial resistance. Improving sepsis outcomes primarily results from prescribing timely antibiotics based on the estimated risk of multidrug resistance (MDR). Previous models grossly overestimated the MDR risk and exacerbated the escalating rates of antimicrobial resistance and excess mortality. The overall goal of this proposed K08 research is to identify common sepsis phenotypes that will enable better prescribing practices and standardized comparisons across hospitals, which will help practicing clinicians, researchers, healthcare institutions, and policy makers. These themes correlate with NIGMS's interest in finding innovative methods and leveraging big data to improve sepsis outcomes. Our three specific aims reflect these goals: (1) establish resistance thresholds for MDR Gram- negative bacilli (GNB) that cause sepsis, (2) assess the impact of sepsis definition on the performance of risk prediction models for MDR GNB, and (3) identify sepsis phenotypes at high risk for MDR GNB in a well-balanced cohort and assess the impact of case mix on risk prediction model performance. We will mathematically derive resistance thresholds that link population resistance rates to individual patient risk of death in sepsis caused by MDR GNB, assess factors that impact prediction performance, and incorporate rich clinical data from 15 hospitals in our healthcare system to identify stable common sepsis phenotypes. Dr. Vazquez Guillamet has training in Infectious Diseases and Critical Care Medicine and experience in antimicrobial resistance in critically ill patients. This proposal will build on her clinical work and previous research experience in finding innovative methods to solve challenging problems at the intersection of infectious diseases and critical care medicine. Dr. Vazquez Guillamet has six career objectives: (1) pursue advanced training in clinical epidemiology; (2) acquire skills in advanced linear regression and multilevel modeling; (3) learn supervised machine learning methods; (4) acquire skills in big data management in healthcare and methods to handle missing data; (5) improve scientific communication, grantsmanship, and leadership, and (6) participate in training in the responsible conduct of research. She will achieve these goals through didactic coursework, hands-on research experience, and active mentoring from experts in Infectious Diseases, Critical Care Medicine, and applied clinical informatics. She will continue to develop innovative methods to mitigate the antimicrobial resistance crisis, especially in critically ill patients, and become an analytics translator at the intersection of clinical medicine and clinical applied informatics. The fertile research environment at Washington University in St. Louis, the experienced mentorship team, and a well-crafted career development plan will enable Dr. Vazquez Guillamet to achieve her long-term goal of becoming an independently funded clinician-investigator utilizing big data to develop applications for risk prediction, surveillance, and outcome comparisons in antimicrobial resistance and sepsis.