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亚胺培南-瑞来巴坦对2015年美国下呼吸道感染患者分离出的革兰阴性杆菌的体外活性——来自SMART全球监测项目的结果

Invitro activity of imipenem-relebactam against gram-negative bacilli isolated from patients with lower respiratory tract infections in the United States in 2015 - Results from the SMART global surveillance program.

作者信息

Lob Sibylle H, Hackel Meredith A, Kazmierczak Krystyna M, Hoban Daryl J, Young Katherine, Motyl Mary R, Karlowsky James A, Sahm Daniel F

机构信息

International Health Management Associates, Inc., 2122 Palmer Drive, Schaumburg, IL, 60173, USA.

International Health Management Associates, Inc., 2122 Palmer Drive, Schaumburg, IL, 60173, USA; Department of Medical Microbiology, College of Medicine, University of Manitoba, 745 Bannatyne Avenue, Winnipeg, Manitoba, R3E 0J9, Canada.

出版信息

Diagn Microbiol Infect Dis. 2017 Jun;88(2):171-176. doi: 10.1016/j.diagmicrobio.2017.02.018. Epub 2017 Mar 2.

Abstract

The β-lactamase inhibitor relebactam inactivates class A β-lactamases, including KPC-type carbapenemases, and class C β-lactamases. Relebactam combined with imipenem is in clinical development for several indications, including hospital-acquired and ventilator-associated pneumonia. Employing CLSI-defined broth microdilution methodology, we evaluated the activities of imipenem-relebactam (using imipenem MIC breakpoints) and comparators against non-Proteeae Enterobacteriaceae (n=853) and Pseudomonas aeruginosa (n=598) isolated from lower respiratory tract infection samples in 20 hospital laboratories in the United States participating in the 2015 SMART (Study for Monitoring Antimicrobial Resistance Trends) global surveillance program. Imipenem-relebactam and imipenem susceptibilities were 97.2% and 91.6% for non-Proteeae Enterobacteriaceae and 93.1% and 68.1% for P. aeruginosa. Relebactam restored imipenem susceptibility to 66.7% and 78.5% of imipenem-non-susceptible non-Proteeae Enterobacteriaceae isolates (n=72) and P. aeruginosa (n=191), respectively. Further development of imipenem-relebactam as therapy for lower respiratory tract infections is warranted given relebactam's ability to restore activity to imipenem against non-susceptible non-Proteeae Enterobacteriaceae and P. aeruginosa.

摘要

β-内酰胺酶抑制剂瑞来巴坦可使包括KPC型碳青霉烯酶在内的A类β-内酰胺酶和C类β-内酰胺酶失活。瑞来巴坦与亚胺培南联合用药正处于针对多种适应症的临床开发阶段,包括医院获得性肺炎和呼吸机相关性肺炎。采用临床和实验室标准协会(CLSI)定义的肉汤微量稀释法,我们评估了亚胺培南-瑞来巴坦(使用亚胺培南的最低抑菌浓度(MIC)断点)及对照药物对从参与2015年SMART(监测抗菌药物耐药性趋势研究)全球监测项目的美国20家医院实验室的下呼吸道感染样本中分离出的非普罗威登斯菌属肠杆菌科细菌(n = 853)和铜绿假单胞菌(n = 598)的活性。对于非普罗威登斯菌属肠杆菌科细菌,亚胺培南-瑞来巴坦和亚胺培南的敏感性分别为97.2%和91.6%;对于铜绿假单胞菌,敏感性分别为93.1%和68.1%。瑞来巴坦使亚胺培南对66.7%的亚胺培南不敏感的非普罗威登斯菌属肠杆菌科细菌分离株(n = 72)和78.5%的亚胺培南不敏感的铜绿假单胞菌分离株(n = 191)恢复了敏感性。鉴于瑞来巴坦能够恢复亚胺培南对不敏感的非普罗威登斯菌属肠杆菌科细菌和铜绿假单胞菌的活性,亚胺培南-瑞来巴坦作为下呼吸道感染治疗药物值得进一步开发。

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