Use of cethromycin, a new ketolide, for treatment of community-acquired respiratory infections
Use of cethromycin, a new ketolide, for treatment of community-acquired respiratory infections
复制标题
DOI：
10.1517/13543784.17.3.387
复制
发表时间：
2008-03-01
影响因子：
6.1
通讯作者：
Sharma, Roopali
中科院分区：
文献类型：
--
作者：
Hammerschlag, Margaret R.;Sharma, Roopali
背景：酮内酯类是大环内酯类的一个子类，专门用于克服大环内酯类耐药的呼吸道病原体。酮内酯缺乏克拉定糖，它被 3-酮基取代。酮内酯与 235 rRNA 亚基的结构域 11 上的二级区域结合。泰利霉素是第一种酮内酯，于 2004 年获得 FDA 批准，用于治疗社区获得性肺炎 (CAP)、慢性支气管炎急性加重 (AECB) 和鼻窦炎。然而，2006 年，在报告严重肝毒性后，FDA 发布了公共卫生建议，随后发出警告。 2007年，治疗AECB和鼻窦炎的适应症从标签中删除。 Cethromycin (ABT-773) 是目前临床开发中唯一的其他酮内酯。目的：回顾目前可获得的塞红霉素数据，包括化学、体外活性、药代动力学、药效学、体内活性和人体治疗研究结果。方法：使用术语酮内酯、ABT-773 和塞红霉素在 PubMed、药物数据库和会议摘要中进行搜索。结果/结论：与泰利霉素相比，红霉素对肺炎链球菌（包括多重耐药菌株、流感嗜血杆菌、卡他莫拉菌、肺炎衣原体、肺炎支原体和嗜肺军团菌）具有相似的组织渗透性、药代动力学和体外活性。只有一项已发表的 CAP 治疗研究比较了赛红霉素 150 mg q.d。 150 mg b.i.d.一项 11 期研究和一项 II/III 期研究已以摘要形式呈现，这两项研究都是非比较性剂量范围研究，表明每日 150 毫克。或 300 mg 每日一次尽管后者的数据有限，但在临床反应和细菌根除方面具有可比性。有关副作用的数据有限，似乎主要是胃肠道副作用。截至撰写本文时，尚未有严重肝毒性的报告。除了治疗 CAP 呼吸道感染外，赛红霉素还可能具有其他用途，包括治疗淋病奈瑟菌和沙眼衣原体以及炭疽杆菌、鼠疫耶尔森菌和土拉弗朗西斯菌等生物恐怖制剂引起的感染。
Background: The ketolides, are a subclass of macrolides, which were designed specifically to overcome macrolide-resistant respiratory pathogens. Ketolides lack the cladinose sugar, which is replaced with a 3-ketone group. Ketolides bind to a secondary region on domain 11 of the 235 rRNA subunit. Telithromycin was the first ketolide to be approved by the FDA in 2004 for treatment of community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB) and sinusitis. However, in 2006, after reports of serious hepatotoxicity, the FDA issued a public health advisory followed by a warning. In 2007 the indications for treatment of AECB and sinusitis were removed from the labeling. Cethromycin (ABT-773) is the only other ketolide currently under clinical development. Objective: To review currently available data on cethromycin, including chemistry, in vitro activity, pharmacokinetics, pharmacodynamics, in vivo activity and results of treatment studies in humans. Methods: A search was made in PubMed, pharmaceutical databases and meeting abstracts using the terms ketolides, ABT-773 and cethromycin. Results/conclusions: Cethromycin has comparable tissue penetration, pharmacokinetics and in vitro activity compared with telithromycin to Streptococcus pneumoniae, including multidrug-resistant isolates, Haemophilus influenzae, Moraxella catarrhalis, Chlamydophila pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila. There is only one published CAP treatment study that compared cethromycin 150 mg q.d. with 150 mg b.i.d. One Phase 11 and a Phase II/III study have been presented in abstract form, both were non-comparative, dose-ranging studies, which suggested that 150 mg q.d. or 300 mg q.d. were comparable in terms of clinical response and bacterial eradication, although data on the latter are limited. Data on side effects are limited and appear to be mainly gastrointestinal. There have been no reports of serious hepatotoxicity at the time of this writing. Cethromycin may have other uses in addition to treatment of CAP respiratory infections, including treatment of infections due to Neisseria gonorrhoeae and Chlamydia trachomatis and bioterrorism agents including Bacillus anthracis, Yersinia pestis and Francisella tularensis.