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临床研发中的新型抗生素,用于治疗产金属β-内酰胺酶的革兰氏阴性菌感染。

New antibiotics in clinical pipeline for treating infections caused by metallo-β-lactamases producing Gram-negative bacteria.

机构信息

Department of Health Sciences (DISSAL), University of Genoa.

Clinica Malattie Infettive, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

出版信息

Curr Opin Infect Dis. 2024 Dec 1;37(6):582-588. doi: 10.1097/QCO.0000000000001056. Epub 2024 Sep 12.

Abstract

PURPOSE OF REVIEW

To discuss novel antibiotics under clinical development, focusing on agents showing in-vitro activity against metallo-β-lactamases (MBL)-producing carbapenem-resistant Gram-negative bacteria (CR-GNB).

RECENT FINDINGS

Currently, only a few approved agents show activity, alone or in synergistic combinations, against MBL-producing CR-GNB. If approved by regulatory agencies in case of favorable results from ongoing (and, for some agents, already completed) phase-3 studies, some novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations could become available in the next few years as additional important options for treating MBL-producing CR-GNB infections. Additional interesting agents that belong both to BL/BLI combinations and to antibiotic classes other than BL and BL/BLI combinations have also shown activity against MBL-producing CR-GNB, with most of them being in early phases of clinical development.

SUMMARY

Improving the use of these novel agents through virtuous antimicrobial stewardship frameworks able to guarantee both the efficacious treatment of infections requiring their use and the avoidance of their use whenever not necessary remains a challenge of utmost importance that should not be overlooked.

摘要

目的综述

讨论处于临床开发阶段的新型抗生素,重点是针对产金属β-内酰胺酶(MBL)的碳青霉烯类耐药革兰氏阴性菌(CR-GNB)具有体外活性的药物。

最新发现

目前,仅有少数几种获批的药物具有针对产 MBL 的 CR-GNB 的活性,无论是单独使用还是联合使用。如果正在进行的(对于一些药物来说,已经完成)的 3 期研究结果有利,并得到监管机构的批准,一些新型β-内酰胺/β-内酰胺酶抑制剂(BL/BLI)联合用药可能会在未来几年内成为治疗产 MBL 的 CR-GNB 感染的重要选择。其他一些属于 BL/BLI 联合用药以及 BL 和 BL/BLI 联合用药以外的抗生素类别,对产 MBL 的 CR-GNB 也具有活性的新型药物也在临床试验的早期阶段。

总结

通过能够保证需要使用这些新型药物的感染得到有效治疗,并避免在不必要时使用这些药物的良性抗菌药物管理框架,提高这些新型药物的使用效果仍然是一个极其重要的挑战,不容忽视。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d056/11556884/e7f8464985d6/coidi-37-582-g001.jpg

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