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新型抗假单胞菌药物治疗囊性纤维化:在小分子 CFTR 调节剂时代仍有必要吗?

New anti-pseudomonal agents for cystic fibrosis- still needed in the era of small molecule CFTR modulators?

机构信息

a Cystic Fibrosis and Chronic Lung Disease , National Heart & Lung Institute, Imperial College London , London , United Kingdom.

出版信息

Expert Opin Pharmacother. 2018 Aug;19(12):1327-1336. doi: 10.1080/14656566.2018.1505864. Epub 2018 Aug 12.

Abstract

INTRODUCTION

Cystic fibrosis is characterized by bacterial lung infection, a majority of adults being chronically infected with Pseudomonas aeruginosa. Treatment is a major challenge, with frequent courses of antibiotics contributing to antimicrobial resistance. New approaches are clearly required. Over the last few years, a major shift in our approach to treating CF has occurred with the availability of the first drugs targeting the CFTR protein and leading to improvements in lung function, weight gain and frequency of exacerbations.

AREAS COVERED

There are emerging, but limited, data exploring the effect these drugs have on airway infections, some studies suggesting a beneficial impact. CFTR modulators probably possess very little direct antimicrobial activity, but both synergy with conventional antibiotics and alternative mechanisms of bacterial killing have been proposed. This article reviews the current published evidence.

EXPERT OPINION

The picture is far from clear concerning the impact of CFTR modulators on lung infections. However, currently, such drugs restore CFTR function incompletely, are most commonly introduced when lung damage is already present, are not suitable for all CF patients and not reimbursed in some areas. Therefore, whatever their eventual anti-infective potential, we need to continue our search for effective anti-pseudomonal therapies for the foreseeable future.

摘要

简介

囊性纤维化的特征是肺部细菌感染,大多数成年人都患有铜绿假单胞菌慢性感染。治疗是一个主要的挑战,频繁使用抗生素会导致抗药性。显然需要新的方法。在过去的几年中,随着靶向 CFTR 蛋白的首批药物的出现,我们治疗 CF 的方法发生了重大转变,这导致了肺功能、体重增加和恶化频率的改善。

涵盖领域

有一些新兴的、但有限的研究探索了这些药物对气道感染的影响,一些研究表明它们具有有益的影响。CFTR 调节剂可能几乎没有直接的抗菌活性,但已提出了与传统抗生素协同作用和替代细菌杀伤机制。本文综述了目前已发表的证据。

专家意见

关于 CFTR 调节剂对肺部感染的影响,情况远不清楚。然而,目前这些药物并不能完全恢复 CFTR 的功能,它们通常在肺部损伤已经存在时引入,并不适用于所有 CF 患者,在某些地区也没有得到报销。因此,无论它们最终的抗感染潜力如何,在可预见的未来,我们仍需要继续寻找有效的抗假单胞菌治疗方法。

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