LMI DRISA, University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, Hanoi, Vietnam.
National Centre of Drug information and Adverse Drug Reaction Monitoring, Hanoi University of Pharmacy, Hanoi, Vietnam.
Int J Antimicrob Agents. 2023 Oct;62(4):106953. doi: 10.1016/j.ijantimicag.2023.106953. Epub 2023 Aug 16.
Pretomanid (PA-824), a novel anti-tuberculosis (TB) nitroimidazoxazine, has been approved for multi-drug-resistant TB treatment for a few years. Pretomanid has been demonstrated to be highly active against Mycobacterium tuberculosis when combined with other anti-TB drugs. This review provides an update of the current knowledge on the modes of action, resistance mechanisms, emergence of drug resistance, and status of antimicrobial susceptibility testing for pretomanid and its relevance for clinical practice. Pretomanid resistance has been reported in in-vitro and animal models but not yet in clinical trials. Pretomanid-resistance-associated mutations have been reported in the fbiA, fbiB, fbiC, fbiD, ddn and fgd1 genes. However, understanding of in-vivo molecular resistance mechanisms remains limited, and complicates the development of accurate antimicrobial susceptibility testing methods for pretomanid. As such, no reference method for antimicrobial susceptibility testing of pretomanid has been established to guide clinical use. Further studies linking specific mutations, in-vitro susceptibility, drug exposure and resistance mechanisms to treatment failure with pretomanid should be prioritized.
氨甲酰吡咯乙酰胺（PA-824）是一种新型抗结核（TB）硝基咪唑嗪类药物，已批准用于治疗耐多药结核病数年。当与其他抗结核药物联合使用时，氨甲酰吡咯乙酰胺已被证明对结核分枝杆菌具有高度活性。本综述介绍了氨甲酰吡咯乙酰胺的作用机制、耐药机制、耐药性的出现以及抗菌药物敏感性检测的现状及其与临床实践的相关性的最新知识。在体外和动物模型中已报告了氨甲酰吡咯乙酰胺的耐药性，但尚未在临床试验中报告。已在 fbiA、fbiB、fbiC、fbiD、ddn 和 fgd1 基因中报告了与氨甲酰吡咯乙酰胺耐药相关的突变。然而，对体内分子耐药机制的理解仍然有限，这使得为氨甲酰吡咯乙酰胺开发准确的抗菌药物敏感性检测方法变得复杂。因此，尚未建立用于指导临床应用的氨甲酰吡咯乙酰胺抗菌药物敏感性检测的参考方法。应优先开展将特定突变、体外药敏性、药物暴露与氨甲酰吡咯乙酰胺治疗失败相关的耐药机制的研究。
