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IID572:一种新型潜在的同类最佳β-内酰胺酶抑制剂。

IID572: A New Potentially Best-In-Class β-Lactamase Inhibitor.

作者信息

Reck Folkert, Bermingham Alun, Blais Johanne, Casarez Anthony, Colvin Richard, Dean Charles R, Furegati Markus, Gamboa Luis, Growcott Ellena, Li Cindy, Lopez Sara, Metzger Louis, Nocito Sandro, Ossola Flavio, Phizackerley Kaci, Rasper Dita, Shaul Jacob, Shen Xiaoyu, Simmons Robert L, Tang Dazhi, Tashiro Kyuto, Yue Qin

机构信息

Novartis Institutes for BioMedical Research , 5300 Chiron Way , Emeryville , California 94608 , United States.

Novartis Institutes for BioMedical Research , 250 Massachusetts Avenue , Cambridge , Massachusetts 02139 , United States.

出版信息

ACS Infect Dis. 2019 Jul 12;5(7):1045-1051. doi: 10.1021/acsinfecdis.9b00031. Epub 2019 Mar 27.

Abstract

Resistance in Gram-negative bacteria to β-lactam drugs is mediated primarily by the expression of β-lactamases, and co-dosing of β-lactams with a β-lactamase inhibitor (BLI) is a clinically proven strategy to address resistance. New β-lactamases that are not impacted by existing BLIs are spreading and creating the need for development of novel broader spectrum BLIs. IID572 is a novel broad spectrum BLI of the diazabicyclooctane (DBO) class that is able to restore the antibacterial activity of piperacillin against piperacillin/tazobactam-resistant clinical isolates. IID572 is differentiated from other DBOs by its broad inhibition of β-lactamases and the lack of intrinsic antibacterial activity.

摘要

革兰氏阴性菌对β-内酰胺类药物的耐药性主要由β-内酰胺酶的表达介导,β-内酰胺类药物与β-内酰胺酶抑制剂(BLI)联合给药是临床上已证实的解决耐药性的策略。不受现有BLI影响的新型β-内酰胺酶正在传播,因此需要开发新型广谱BLI。IID572是一种新型的二氮杂双环辛烷(DBO)类广谱BLI,能够恢复哌拉西林对耐哌拉西林/他唑巴坦临床分离株的抗菌活性。IID572与其他DBO的区别在于其对β-内酰胺酶的广泛抑制以及缺乏内在抗菌活性。

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