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非结核分枝杆菌肺病与 SPR720 的潜在作用。

Nontuberculous mycobacterial pulmonary disease and the potential role of SPR720.

机构信息

Oregon Health & Science University, Portland, Oregon, USA.

Medical University of South Carolina, Charleston, South Carolina, USA.

出版信息

Expert Rev Anti Infect Ther. 2023 Jul-Dec;21(11):1177-1187. doi: 10.1080/14787210.2023.2270158. Epub 2023 Nov 8.

Abstract

INTRODUCTION

Nontuberculous mycobacteria infect patients who have structural lung disease or those who are immunocompromised. Nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing in prevalence. Treatment guidelines for complex (MAC) pulmonary disease involve a three-drug regimen with azithromycin, ethambutol, and rifampin, and those of complex (MAB) pulmonary disease involve a combination of three or more antimicrobials including macrolides, amikacin, and a β-lactam or imipenem. However, these regimens are poorly tolerated and generally ineffective.

AREAS COVERED

SPR720 is a novel therapeutic agent that has demonstrated activity against a range of NTM species, including MAC and MAB. Encouraging and pre-clinical data demonstrate that SPR720 is active both alone and in combination with standard-of-care agents, with no evidence of cross-resistance to such agents. It is generally well tolerated with mainly gastrointestinal and headache adverse events of mild or moderate severity.

EXPERT OPINION

Management of NTM-PD is challenging for many reasons including length of therapy, poor efficacy, drug intolerance, recurrence, and resistance development. The current antimicrobial management options for NTM-PD are limited in number and there exists a large unmet need for new treatments. SPR720 has encouraging data that warrant further study in the context of a multidrug regimen.

摘要

简介

非结核分枝杆菌感染患有结构性肺病或免疫功能低下的患者。非结核分枝杆菌肺病(NTM-PD)的患病率正在上升。复杂(MAC)肺病的治疗指南包括使用阿奇霉素、乙胺丁醇和利福平的三药方案,而复杂(MAB)肺病的治疗则涉及包括大环内酯类、阿米卡星和β-内酰胺类或亚胺培南在内的三种或更多种抗生素的联合治疗。然而,这些方案的耐受性差,通常无效。

涵盖领域

SPR720 是一种新型治疗药物,对多种 NTM 物种(包括 MAC 和 MAB)均具有活性。令人鼓舞的临床前数据表明,SPR720 无论是单独使用还是与标准护理药物联合使用都具有活性,并且与这些药物之间没有交叉耐药性的证据。它的耐受性通常较好,主要有胃肠道和头痛等不良反应,其严重程度为轻度或中度。

专家意见

由于治疗时间长、疗效差、药物不耐受、复发和耐药性的发展等诸多原因,NTM-PD 的管理具有挑战性。目前,NTM-PD 的抗菌药物管理选择数量有限,新治疗方法存在巨大的未满足需求。SPR720 有令人鼓舞的数据,值得在多药治疗方案中进一步研究。

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