Increasingly resistant Enterobacteriaceae have emerged as a health threat in both hospital and community settings. Infections of the urinary tract, once often treated with oral agents in the community, are requiring increased hospitalization and use of intravenously administered agents for effective treatment. These isolates often carry extended spectrum β-lactamases (ESBLs) and carbapenemases that necessitate the need for an inhibitor to cover a broad range of β-lactamases. ETX1317 is a novel diazabicyclooctane class serine β-lactamase inhibitor that restores the antibacterial activity of several classes of β-lactams, including third-generation cephalosporins such as cefpodoxime. ETX1317 is currently being developed as an orally available prodrug, ETX0282, to be administered with cefpodoxime proxetil (CPDP). The combination has demonstrated oral efficacy in murine models of infection. Pharmacokinetics established in preclinical species and pharmacokinetic/pharmacodynamic attributes suggest the orally administered combination ETX0282 + CPDP could serve as an effective treatment option against contemporary ESBL and carbapenemase-producing Enterobacteriaceae.

中文翻译：

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β-内酰胺酶抑制剂ETX1317及其口服前药ETX0282的药代动力学/药效学测定和临床前药代动力学。

在医院和社区环境中，抵抗力增强的肠杆菌科细菌已成为对健康的威胁。一旦在社区中经常用口服药物治疗尿路感染，就需要增加住院治疗并使用静脉内给药的药物进行有效治疗。这些分离物通常带有广谱的β-内酰胺酶（ESBLs）和碳青霉烯酶，因此需要抑制剂来覆盖广泛的β-内酰胺酶。ETX1317是一种新型的二氮杂双环辛烷类丝氨酸β-内酰胺酶抑制剂，可恢复包括第三代头孢菌素（如头孢泊肟）在内的多种β-内酰胺类的抗菌活性。ETX1317目前正在开发为口服可用的前药ETX0282，与头孢泊肟肟前列醇（CPDP）一起给药。该组合已证明在鼠类感染模型中具有口服功效。在临床前物种中建立的药代动力学和药代动力学/药效学属性表明，口服联合给药ETX0282 + CPDP可作为对抗当代ESBL和碳青霉烯酶产生的有效治疗选择肠杆菌科。