A Narrative Review of Bedaquiline and Delamanid: New Arsenals Against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis

IF 2.6 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis Pub Date : 2024-09-04 DOI:10.1002/jcla.25091

Nazanin Ahmad Khosravi, Mehrandokht Sirous, Azar Dokht Khosravi, Morteza Saki

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引用次数: 0

Abstract

Background

The treatment of multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) is a formidable challenge. Treatment of MDR- and XDR-TB using bedaquiline (BDQ) and delamanid (DLM), two newly introduced medications, is steadily increasing. This narrative review aimed to present a concise overview of the existing information regarding BDQ and DLM, and elucidate their antimicrobial characteristics, resistance mechanisms, synergism with other drugs, and side effects.

Methods

To collect the required information about the antimicrobial properties, a search for scientific evidence from the Scopus, PubMed, and Embase databases was performed, and all recently published articles up to May 2024 were considered.

Results

BDQ had potent antimicrobial effects on various types of nontuberculous mycobacteria (NTM), including rapid-growing and slow-growing species, and MDR/XDR Mycobacterium tuberculosis. The mechanisms of BDQ resistance in M. tuberculosis primarily involve mutations in three genes: atpE, mmpR (Rv0678) and pepQ. BDQ may have synergistic effects when combined with DLM, pyrazinamide, and pretomanid/linezolid. BDQ has a low incidence of side effects. The use of BDQ may prolong the QTc interval. Similarly, DLM showed potent antimicrobial effects on NTM and MDR/XDR M. tuberculosis. The main resistance mechanisms to DLM are induced by mutations in fbiA, fbiB, fbiC, fgd1, and ddn genes. The DLM had synergistic effects with BDQ and moxifloxacin. The DLM also has few side effects in some patients including QTc prolongation.

Conclusion

BDQ and DLM are suitable antibiotics with few side effects for the treatment of MDR/XDR-TB. These antibiotics have synergistic effects when combined with other antituberculosis drugs.

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贝达喹啉和德拉马尼的叙述性综述：对抗耐多药和广泛耐药结核分枝杆菌的新武器

背景耐多药（MDR-）和广泛耐药结核病（XDR-TB）的治疗是一项艰巨的挑战。使用贝达喹啉（BDQ）和地拉那米（DLM）这两种新引进的药物治疗 MDR- 和 XDR-TB 的病例正在稳步增加。本综述旨在简明扼要地概述有关贝达喹啉和地拉那米的现有信息，并阐明这两种药物的抗菌特性、耐药机制、与其他药物的协同作用以及副作用。方法为了收集所需的抗菌特性信息，从 Scopus、PubMed 和 Embase 数据库中搜索科学证据，并考虑了截至 2024 年 5 月的所有近期发表的文章。结果 BDQ 对各种类型的非结核分枝杆菌（NTM），包括快速生长和缓慢生长的菌种，以及 MDR/XDR 结核分枝杆菌具有强效抗菌作用。结核分枝杆菌对 BDQ 产生抗药性的机制主要涉及三个基因的突变：atpE、mmpR (Rv0678) 和 pepQ。BDQ与DLM、吡嗪酰胺和pretomanid/linezolid联用时可能会产生协同效应。BDQ 的副作用发生率较低。使用 BDQ 可能会延长 QTc 间期。同样，DLM 对 NTM 和 MDR/XDR 型结核杆菌也有很强的抗菌作用。对 DLM 的主要耐药机制是由 fbiA、fbiB、fbiC、fgd1 和 ddn 基因突变诱导的。DLM 与 BDQ 和莫西沙星具有协同作用。DLM 对一些患者的副作用也很小，包括 QTc 延长。结论 BDQ 和 DLM 是治疗 MDR/XDR-TB 的合适抗生素，副作用小。这些抗生素与其他抗结核药物合用时具有协同作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Clinical Laboratory Analysis 医学-医学实验技术

CiteScore

5.60

自引率

7.40%

发文量

584

审稿时长

6-12 weeks

期刊介绍： Journal of Clinical Laboratory Analysis publishes original articles on newly developing modes of technology and laboratory assays, with emphasis on their application in current and future clinical laboratory testing. This includes reports from the following fields: immunochemistry and toxicology, hematology and hematopathology, immunopathology, molecular diagnostics, microbiology, genetic testing, immunohematology, and clinical chemistry.