Big Data- Epidemiology of Antimicrobial Resistance

大数据-抗菌药物耐药性流行病学

• 批准号: 10250942
• 负责人: Sameer Kadri
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10250942
• 关键词: Academic Medical Centers; Americas; Aminoglycosides; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Antimicrobial Resistance; Bacteremia; Big Data; Blood; Carbapenems; Ceftazidime; Centers for Disease Control and Prevention (U.S.); Cerebrospinal Fluid; Clinical; Colistin; Collaborations; Communicable Diseases; Communities; Consensus; Correlation Studies; Critical Care; Data; Development; Diagnostic; Electronic Health Record; Fluoroquinolones; Funding; Health; Hospitals; In Vitro; Infection; Medicine; Minimum Inhibitory Concentration measurement; Outcome; Outcomes Research; Patients; Pattern; Phenotype; Polymyxin B; Population; Predisposition; Prevalence; Research Personnel; Resistance; Role; Sepsis; Societies; Staphylococcus aureus; Stream; United States; United States National Institutes of Health; Work; antimicrobial; base; beta-Lactams; clinical database; clinically relevant; drug resistant pathogen; epidemiologic data; meetings; mortality risk; novel; pathogen; pathogenic bacteria; point-of-care diagnostics; repository; tigecycline; trend

Co-resistance necessitating use of less effective or relatively toxic reserve antibiotics (aminoglycosides, tigecycline and colistin/polymyxin B) may worsen survival. We investigated difficult-to-treat resistance (DTR) in gram-negative bloodstream infections (GNBSIs) defined by absence of susceptibility to all first-line agents (carbapenems, beta-lactams and fluoroquinolones (FQ) using a large clinical database of US hospitals. We found that survival in antimicrobial-resistant GNBSI is highly contingent on presence of active first-line option(s); DTR limits treatment options to reserve agents, including aminoglycosides, which are far from universally active. DTR remained infrequent (1%) among GNBSI, but occurred at half of the hospitals examined and across all US regions. This work has been presented at the Annual Meetings of the Infectious Diseases Society of America and Society of Critical Care Medicine. We went on to validate our findings using the Cerner Health facts repository of electronic health records. As part of the NIH Antimicrobial Resistance Outcomes Research Initiative (NIH-ARORI), we also went on to study the landscape of emerging antibiotics to understand their real-world use and demand. We found that ceftazidime-avibactam use increased several fold replacing colistin use, however overall use was still modest. As part of an FDA-funded initiative, we determined that treatment opportunities for difficult-to-treat antibiotic resistant pathogens in US hospitals remains small, suggesting that non-revenue based strategies might be necessary to sustain antibiotic development. As part of ongoing work, we are performing national extrapolations to understand recent trends in difficult-to-treat resistance, conducting an analysis of burden and impact of inappropriate antibiotic therapy in bacteremia and sepsis and are also attempting to determine whether shorter courses of therapy are sufficient in clinically suspected serious infection when no pathogens are identified, as a move to promote stewardship. As part of the NIH Antimicrobial Resistance Outcomes Research Initiative (NIH-ARORI), we determined that one in every five patients with bloodstream infection in US hospitals receives empiric antibiotic therapy that is discordant with in vitro susceptibilities. This practice was prevalent and similar across hospital types. Bacteremic patients who received in vitro-discordant empiric therapy displayed a higher mortality risk than receipients of concordant therapy. S. aureus and Enterobacterales and their resistance phenotypes account for the overwhelming majority of burden and impact of in vitro-discordant therapy, warranting development and wide implementation of effective rapid point-of-care diagnostics, especially those targeting these pathogens and their resistance phenotypes. In collaboration with the investigators at the Harvard Department of Population Medicine, we used larger electronic health record data from over a hundred U.S. hospitals and determined that despite the extensive use of broad-spectrum empiric antibiotic therapy for community-onset sepsis, the prevalence of antibiotic resistant pathogens warranting such therapy is small. Rapid diagnostics targeting resistance phenotypes may have a role in enhancing antibiotic stewardship in sepsis.

共耐药导致需要使用疗效较低或毒性相对较强的储备抗生素（氨基糖苷类、替加环素和粘菌素/多粘菌素B）可能会使生存率恶化。我们使用美国医院的大型临床数据库，研究了革兰氏阴性血流感染（GNBSI）中的难治性耐药（DTR），定义为对所有一线药物（碳青霉烯类、β-内酰胺类和氟喹诺酮类（FQ））均不敏感。我们发现，抗微生物耐药GNBSI患者的生存率高度依赖于是否存在活性一线药物选择; DTR将治疗选择限制在储备药物，包括氨基糖苷类药物，这些药物远非普遍有效。DTR在GNBSI中仍然不常见（1%），但在接受检查的一半医院和美国所有地区都发生了DTR。这项工作已在美国传染病学会和重症监护医学学会年会上发表。 我们继续使用Cerner Health电子健康记录事实库验证我们的发现。 作为NIH抗菌素耐药性成果研究计划（NIH-ARORI）的一部分，我们还继续研究了新兴抗生素的前景，以了解它们的实际使用和需求。我们发现，头孢他啶-阿维巴坦的使用增加了数倍，取代了粘菌素的使用，但总体使用仍然适度。作为FDA资助的一项计划的一部分，我们确定，在美国医院中，难以治疗的抗生素耐药病原体的治疗机会仍然很小，这表明非收入为基础的战略可能是必要的，以维持抗生素的发展。作为正在进行的工作的一部分，我们正在进行国家外推，以了解难以治疗的耐药性的最新趋势，对菌血症和脓毒症中不适当的抗生素治疗的负担和影响进行分析，并试图确定在没有发现病原体的情况下，临床疑似严重感染的较短疗程是否足够，作为促进管理的一项举措。 作为美国国立卫生研究院抗菌药物耐药性结果研究计划（NIH-ARORI）的一部分，我们确定，在美国医院中，每五名血流感染患者中就有一名接受与体外耐药性不一致的经验性抗生素治疗。这种做法很普遍，在不同类型的医院中也很相似。菌血症患者接受体外不一致的经验性治疗显示出较高的死亡风险比一致的治疗。S.金黄色葡萄球菌和肠球菌目的病原体及其耐药表型是体外不一致疗法的绝大多数负担和影响，阻碍了有效的快速床旁诊断的开发和广泛实施，特别是那些靶向这些病原体及其耐药表型的诊断。 我们与哈佛人口医学系的研究人员合作，使用了来自100多家美国医院的更大的电子健康记录数据，并确定尽管广泛使用广谱经验性抗生素治疗社区发病的脓毒症，但抗生素耐药病原体的患病率很小。针对耐药表型的快速诊断可能在增强脓毒症的抗生素管理方面发挥作用。