Multidrug-resistant (MDR) bacterial infections are a serious threat to public health. Among the most alarming resistance trends is the rapid rise in the number and diversity of β-lactamases, enzymes that inactivate β-lactams, a class of antibiotics that has been a therapeutic mainstay for decades. Although several new β-lactamase inhibitors have been approved or are in clinical trials, their spectra of activity do not address MDR pathogens such as Acinetobacter baumannii. This report describes the rational design and characterization of expanded-spectrum serine β-lactamase inhibitors that potently inhibit clinically relevant class A, C and D β-lactamases and penicillin-binding proteins, resulting in intrinsic antibacterial activity against Enterobacteriaceae and restoration of β-lactam activity in a broad range of MDR Gram-negative pathogens. One of the most promising combinations is sulbactam-ETX2514, whose potent antibacterial activity, in vivo efficacy against MDR A. baumannii infections and promising preclinical safety demonstrate its potential to address this significant unmet medical need.

中文翻译：

---

ETX2514是广谱β-内酰胺酶抑制剂，用于治疗耐药性革兰氏阴性细菌，包括鲍曼不动杆菌。

耐多药（MDR）细菌感染严重威胁公共健康。最令人担忧的耐药性趋势之一是β-内酰胺酶（使β-内酰胺类失活的酶）的数量和多样性迅速增加，β-内酰胺类是数十年来一直是治疗性支柱的一类抗生素。尽管几种新的β-内酰胺酶抑制剂已经被批准或正在临床试验中，但是它们的活性谱不能解决MDR病原体，例如鲍曼不动杆菌。该报告描述了广谱丝氨酸β-内酰胺酶抑制剂的合理设计和表征，该抑制剂可有效抑制临床上相关的A，C和D类β-内酰胺酶和青霉素结合蛋白，从而对肠杆菌科产生固有的抗菌活性并恢复β-内酰胺。在广泛的MDR革兰氏阴性病原体中具有活性。