抗结核新药普托马尼研究进展

由于对一线药物存在很大的耐药性,广泛耐药结核病和多药耐药结核病往往很难完全治愈。普托马尼（Pretomanid,PA-824）是目前临床试验评估中的治疗耐药结核分枝杆菌的优选药物之一,该药通过抑制细胞壁的形成和呼吸中毒两种机制,对复制型和静止型结核分枝杆菌均表现出显著的杀菌活性。本文通过探讨PA-824释放活性氮物质对结核分枝杆菌产生强氧化作用和细胞毒作用、延长早期杀菌活性、降低患者痰中结核分枝杆菌载量的速度、引起可控性不良反应等作用,全面了解该药物的抗结核作用机理,包括抑制结核分枝杆菌菌株耐药性的发展、缩短结核病治疗的持续时间等。本文还阐述了PA-824、贝达喹啉和利奈唑胺联合治疗,该联合方案具有相当的杀菌活性,在杀灭细菌和抑制耐药性方面具有协同或相加的作用潜力,对XDR-TB或者MDR-TB具有更好的治疗效果。有望进一步改善目前结核病的治疗现状

Research progress on new anti-tuberculosis drug pretomanid

Due to the great resistance to first-line drugs, XDR-TB and MDR-TB are often difficult to cure completely. Pretomanid,PA-824 is one of the preferred drugs evaluated in clinical trials for the treatment of drug-resistant Mycobacterium tuberculosis. By inhibiting cell wall formation and respiratory toxicity, Pretomanid shows significant bactericidal activity against both replicative and stationary Mycobacterium tuberculosis. This article explores the effects of PA-824 on releasing active nitrogen substances and producing strong oxidative and cytotoxicity to Mycobacterium tuberculosis, prolonging early bactericidal activity, reducing the speed of Mycobacterium tuberculosis load in patients' sputum, and causing controllable adverse reactions, and comprehensively understand the anti-tuberculosis mechanism of pretomanid, including inhibiting the development of drug resistance of Mycobacterium tuberculosis strains, shortening the duration of tuberculosis treatment, and so on. The combination of pretomanid PA-824, bedaquinoline and linezolid, which has synergistic or additive potential in killing bacteria and inhibiting drug resistance, is also described, and is expected to further improve current TB treatment outcomes.