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新与改良?革兰氏阳性菌新型抗生素的综述。

New and improved? A review of novel antibiotics for Gram-positive bacteria.

机构信息

Infection Control Programme, Geneva University Hospitals, Geneva, Switzerland; Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland.

Infectious Diseases Institute, Rambam Health Care Campus, Haifa, Israel; The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.

出版信息

Clin Microbiol Infect. 2017 Oct;23(10):697-703. doi: 10.1016/j.cmi.2017.06.010. Epub 2017 Jun 19.

Abstract

BACKGROUND

The number of antibiotics in the pipeline targeting Gram-positive pathogens has increased in recent years.

AIMS

This narrative review aims to provide a summary of existing evidence on efficacy, microbiological spectrum and safety of novel systemic antibiotics that have either recently been licensed or completed phase III trials, and possess activity predominantly against Gram-positive organisms.

SOURCES

A review of the published literature via the MEDLINE database was performed. In addition, ongoing trials were identified through a search of the clinical trial registration platform clinicaltrials.gov, and when necessary, pharmaceutical companies responsible for the development of the drug were contacted for further information.

CONTENT

Data on development, microbiological spectrum, pharmacokinetic/pharmacodynamic properties, clinical efficacy, safety and cost are presented for the new cephalosporins ceftaroline and ceftobiprole; the lipoglycopeptides dalbavancin, oritavancin and telavancin; the fluoroquinolones delafloxacin, nemonoxacin and zabofloxacin; the dihydrofolate-reductase inhibitor iclaprim; the pleuromutilin lefamulin; and the tetracycline omadacycline.

IMPLICATIONS

Although promising, these new antibiotics have so far been tested in non-severe infections whose treatment is generally uncomplicated and whose aetiologies were not predominantly multidrug-resistant pathogens. None of the new antibiotics have shown superiority to standard care, and none have been investigated for patient-relevant outcomes. Safety and pharmacokinetic data continue to be lacking. How these new drugs are to be integrated into the current armamentarium remains to be established.

摘要

背景

近年来,针对革兰氏阳性病原体的抗生素数量有所增加。

目的

本综述旨在总结新的系统抗生素的现有疗效、微生物谱和安全性证据,这些抗生素最近已获得许可或完成了 III 期试验,并且主要对革兰氏阳性菌具有活性。

资料来源

通过 MEDLINE 数据库对已发表的文献进行了综述。此外,通过在临床试验注册平台 clinicaltrials.gov 上搜索,确定了正在进行的试验,并在必要时联系负责药物开发的制药公司以获取更多信息。

内容

介绍了新型头孢菌素头孢洛林、头孢托罗匹酯;脂糖肽类达巴万星、奥他万星和替拉万星;氟喹诺酮类药物德拉沙星、萘莫沙星和扎布沙星;二氢叶酸还原酶抑制剂依拉普立;截短侧耳素类利福霉素 lefamulin;以及四环素类 omadacycline 的研发、微生物谱、药代动力学/药效学特性、临床疗效、安全性和成本数据。

意义

尽管这些新抗生素很有前景,但迄今为止,它们仅在非严重感染中进行了测试,这些感染的治疗通常不复杂,且病因并非主要为多药耐药病原体。这些新抗生素均未显示优于标准治疗,也未针对患者相关结局进行研究。安全性和药代动力学数据仍缺乏。这些新药如何融入当前的治疗方案仍有待确定。

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