Applied Research in Antimicrobial Resistance: Studies of Susceptibility Testing

抗菌素耐药性的应用研究：药敏试验研究

• 批准号: 7415362
• 负责人: LISA SAIMAN
• 金额: $ 30万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2010-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7415362
• 关键词: Applied; Research; Antimicrobial; Resistance; Studies

DESCRIPTION (provided by applicant): Despite the large numbers of effective antibiotics in use today, the 'post-antimicrobial era' has been looming for well over a decade as patients, particularly in intensive care units (ICUs), are increasingly developing infections caused by multidrug-resistant (MDR) pathogens. Such infections are associated with increased mortality, increased morbidity, and increased cost. Gram negative bacilli (GNB), such as Pseudomonas aeruginosa, Klebsiella pneumonia and Acinetobacter spp. (the pathogens of interest in this project), may become resistant to all antimicrobial agents as determined by routine susceptibility testing. The goals of this project are to: 1) determine strategies to improve the treatment of patients infected with MDR-GNB and thus improve clinical and microbiological outcomes of such infections, (2) assess which laboratory algorithms for in vitro antimicrobial susceptibility testing most closely correlate with improved outcomes for MDR-GNB infections, and (3) evaluate how healthcare professionals actually use in vitro susceptibility data to choose and modify treatment regimens for MDR-GNB infections. The research design is a prospective observational study of ICU patients with hospital-acquired pneumonia and bloodstream infections caused by MDR-GNB at New York- Presbyterian Hospital (NYPH) in New York City, the epicenter of MDR-GNB infections. NYPH is the largest medical center in NYC and has 16 ICUs, 383 ICU beds, and 14,800 patients admitted to the ICU each year of whom approximately 40-50 develop MDR-GNB infections. The specific aims and research methods are as follows: Aim 1 will observe the treatment strategies used for MDR-GNB infections and determine the outcomes of subjects with MDR-GNB infections associated with selected treatment regimens and as compared with the outcomes of subjects with non-MDR-GNB infections by performing a nested case-control study. Aim 2 will determine the in vitro susceptibility testing strategies (performed on MDR-GNB from Aim 1) that best predict successful clinical and microbiologic outcomes and potentially lead to different treatment choices. Testing strategies will include ancillary testing currently used by NYPH clinical microbiology laboratories (e.g., Etest for colistin and tigecycline) as well as research assays (e.g., reference broth microdilution synergy studies, Etest synergy studies, and minimal bactericidal concentration testing). Aim 3 will survey healthcare professionals at NYPH to determine their knowledge, attitudes, and practices regarding antimicrobial susceptibility testing strategies and determine factors associated with the use of test results. To do so, an electronic, anonymous survey will be administered to 150 ICU physicians, infectious diseases sub-specialists, and clinical pharmacists. The carefully conducted observational studies proposed in this project, supplemented by potentially clinically relevant in vitro susceptibility testing, hold the greatest promise to improve the treatment of patients infected with MDR-GNB. Patients, particularly in intensive care units, are increasingly developing infections caused by multidrug-resistant organisms. These infections are associated with increased mortality, increased morbidity, and increased cost. Carefully conducted observational studies and clinically relevant in vitro antimicrobial susceptibility testing, hold the greatest promise to improve the treatment of patients infected with mutidrug-resistant organisms.

描述（由申请人提供）：尽管当今使用中有大量有效的抗生素，但随着患者，尤其是在重症监护病房（ICU）中，“抗菌后时代”已经迫在眉睫，已经迫在眉睫，越来越多地发展由多种耐药（MDR）病原体引起的感染。这种感染与死亡率增加，发病率增加和成本增加有关。革兰氏阴性杆菌（GNB），例如铜绿假单胞菌，肺炎克雷伯氏菌和杆菌属。 （该项目感兴趣的病原体）可能会因常规敏感性测试确定对所有抗菌剂的抗性。该项目的目标是：1）确定改善感染MDR-GNB的患者治疗的策略，从而改善了此类感染的临床和微生物学结果，（2）评估哪些实验室算法在体外抗菌易感性测试中最密切相关地选择了与MIMDR-GNB Intection Intrace Introcation（3）相关性的（3），以实现MIMDR-GNEB的影响（3），该研究实际上是在治疗的，（3）并修改MDR-GNB感染的治疗方案。该研究设计是对ICU医院获得性肺炎和血流感染ICU患者在纽约市纽约 - 长老会医院（NYPH）引起的前瞻性观察性研究。 NYPH是纽约市最大的医疗中心，每年有16个ICU，383张ICU床和14,800名患者，其中大约有40-50次患有MDR-GNB感染。具体目的和研究方法如下：AIM 1将观察用于MDR-GNB感染的治疗策略，并确定与选定治疗方案相关的MDR-GNB感染受试者的结果，并与非MDR-GNB感染的受试者通过进行嵌套的病例控制研究相比。 AIM 2将确定最能预测成功的临床和微生物学结果的体外敏感性测试策略（AIM 1），并有可能导致不同的治疗选择。测试策略将包括NYPH临床微生物学实验室目前使用的辅助测试（例如，Colistin和tigecycline的Etest）以及研究测定（例如，参考肉汤微稀释协同研究，ESTEST协同研究，以及最少的杀菌浓度测试）。 AIM 3将调查NYPH的医疗保健专业人员，以确定他们的知识，态度和实践有关抗菌敏感性测试策略的实践，并确定与使用测试结果相关的因素。为此，将对150名ICU医师，传染病亚科医师和临床药剂师进行电子匿名调查。在该项目中提出的精心进行的观察性研究，并补充了潜在的临床相关体外易感性测试，具有改善感染MDR-GNB的患者的治疗的最大希望。患者，特别是在重症监护病房中，正在越来越多地发展由多种耐药生物引起的感染。这些感染与死亡率增加，发病率增加和成本增加有关。精心进行了观察性研究和临床相关的体外抗菌易感性测试，具有改善感染耐杀虫剂生物体的患者的最大希望。