Big Data- Epidemiology of Antimicrobial Resistance

共同耐药需要使用效果较差或相对毒性较高的备用抗生素(氨基糖苷类、替加环素和粘菌素/多粘菌素B)，可能会恶化存活率。我们使用美国医院的大型临床数据库调查了革兰氏阴性血流感染(GNBSI)中的难治耐药性(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))不敏感。我们发现，耐药GNBSI的存活率高度取决于是否存在有效的一线选择(S)；DTR将治疗选择限制为储备药物，包括氨基糖苷类药物，这些药物远未普遍有效。DTR在GNBSI中仍然很少见(1%)，但在接受检查的一半医院和美国所有地区发生。这项工作已经在美国传染病学会和重症监护医学会的年度会议上发表。 我们继续使用Cerner Health FACTS电子健康记录库来验证我们的发现。 作为NIH抗菌素耐药性结果研究倡议(NIH-ARORI)的一部分，我们还继续研究了新兴抗生素的情况，以了解它们在现实世界中的使用和需求。我们发现，头孢他啶-阿巴坦的使用量比粘菌素的使用量增加了几倍，但总体使用量仍然不大。作为FDA资助的一项倡议的一部分，我们确定，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，这表明可能有必要采取非营收战略来维持抗生素的开发。作为正在进行的工作的一部分，我们正在进行全国外推，以了解难以治疗的耐药性的最新趋势，对菌血症和败血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，较短的疗程是否足以治疗临床疑似严重感染，作为促进管理的举措。 作为NIH抗菌素耐药性结果研究倡议(NIH-ARORI)的一部分，我们确定，美国医院每五名血液感染患者中就有一人接受与体外敏感性不一致的经验性抗生素治疗。这种做法在不同类型的医院中很普遍，也很相似。接受体外非协调性经验性治疗的细菌血症患者显示出比接受协调性治疗的患者更高的死亡风险。金黄色葡萄球菌和肠杆菌属及其耐药表型是体外非协调性治疗的绝大多数负担和影响因素，需要开发和广泛实施有效的快速医疗点诊断方法，特别是针对这些病原体及其耐药表型的诊断方法。 与哈佛大学人口医学部的研究人员合作，我们使用了来自100多家美国医院的更大的电子健康记录数据，并确定尽管广谱经验性抗生素疗法被广泛用于社区发作性脓毒症，但需要这种疗法的抗生素耐药病原体的流行率很低。针对耐药表型的快速诊断可能在加强脓毒症的抗生素管理方面发挥作用。

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.