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碳青霉烯类药物抗结核分枝杆菌:证据综述

Carbapenems against Mycobacterium tuberculosis: a review of the evidence.

作者信息

Jaganath D, Lamichhane G, Shah M

机构信息

Department of Pediatrics, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

Center for Tuberculosis Research, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

出版信息

Int J Tuberc Lung Dis. 2016 Nov;20(11):1436-1447. doi: 10.5588/ijtld.16.0498.

Abstract

Carbapenems, a more recent β-lactam class, represent a unique anti-tuberculosis option, as emerging evidence demonstrates that they target the Mycobacterium tuberculosis cell wall and β-lactamase. This provides a potentially new agent against M. tuberculosis, in particular for multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB), where options are limited. In this review, we examine the current evidence on the activity of carbapenems against M. tuberculosis. The predominance of work is in vitro, and suggests that carbapenems kill M. tuberculosis at least in the active phase, with possible greater potency with the addition of a β-lactamase inhibitor. The few in vivo and clinical studies suggest that there are benefits and that they are generally tolerated, although the variability in duration, dosing, and background regimen and lack of pharmacokinetic analyses limit interpretation of efficacy. We outline further areas of research to better understand the role of carbapenems to add a needed new agent to the treatment of MDR- and XDR-TB.

摘要

碳青霉烯类是较新的一类β-内酰胺类抗生素,是一种独特的抗结核选择,因为新出现的证据表明它们作用于结核分枝杆菌细胞壁和β-内酰胺酶。这为对抗结核分枝杆菌提供了一种潜在的新型药物,特别是对于多药耐药(MDR)和广泛耐药(XDR)结核病(TB),这类疾病的治疗选择有限。在本综述中,我们研究了目前关于碳青霉烯类对结核分枝杆菌活性的证据。现有研究主要是体外研究,表明碳青霉烯类至少在活跃期可杀死结核分枝杆菌,添加β-内酰胺酶抑制剂后可能效力更强。少数体内和临床研究表明,使用碳青霉烯类有一定益处且通常耐受性良好,不过疗程、给药剂量、背景治疗方案的差异以及缺乏药代动力学分析限制了对疗效的解读。我们概述了进一步的研究领域,以更好地了解碳青霉烯类的作用,为耐多药和广泛耐药结核病的治疗增添一种急需的新型药物。

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