Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy.
UO Clinica Malattie Infettive, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Expert Rev Anti Infect Ther. 2024 Nov;22(11):965-976. doi: 10.1080/14787210.2024.2407068. Epub 2024 Sep 26.
Several novel agents are in advanced stages of clinical development, potentially expanding our treatment options against third- and fourth-generation cephalosporin-resistant and carbapenem-resistant Gram-negative bacteria (GNB), including those pathogens for which the current number of effective treatments is limited.
This review focuses on agents that have completed or ongoing phase-3 studies. A PubMed search was conducted up to 31 May 2024.
Novel agents in late-stage clinical development belong to the β-lactam or β-lactam/β-lactamase inhibitor combinations class and display variable antimicrobial activity depending on the specific β-lactamases expressed by GNB, particularly carbapenemases. While many of these novel agents demonstrate in vitro activity against carbapenem-resistant GNB, their efficacy has mainly been evaluated in phase-3 randomized controlled trials (RCT) for infections caused by carbapenem-susceptible GNB. Although evidence from real-world observational studies is generally less robust than that from RCT, it could be crucial for updating clinical guidelines on treating carbapenem-resistant GNB with these new agents in the absence of dedicated RCT.
几种新型药物正处于临床开发的后期阶段，有可能扩大我们针对第三代和第四代头孢菌素耐药和碳青霉烯类耐药革兰氏阴性菌（GNB）的治疗选择，包括那些目前有效治疗方法有限的病原体。
本综述重点介绍已完成或正在进行的 3 期研究的药物。截至 2024 年 5 月 31 日，进行了一项 PubMed 检索。
处于临床开发后期的新型药物属于β-内酰胺类或β-内酰胺/β-内酰胺酶抑制剂组合类，根据 GNB 表达的特定β-内酰胺酶，表现出不同的抗菌活性，尤其是碳青霉烯酶。虽然这些新型药物中的许多在体外对碳青霉烯类耐药的 GNB 具有活性，但它们的疗效主要在针对碳青霉烯类敏感的 GNB 感染的 3 期随机对照试验（RCT）中进行了评估。尽管来自真实世界观察性研究的证据通常不如 RCT 稳健，但在缺乏专门的 RCT 的情况下，对于更新使用这些新药物治疗碳青霉烯类耐药 GNB 的临床指南可能至关重要。
