Massachusetts College of Pharmacy and Health Sciences, Worcester, MA, USA.
Ann Pharmacother. 2010 Feb;44(2):352-9. doi: 10.1345/aph.1M351. Epub 2010 Jan 13.
To evaluate the efficacy and safety of fidaxomicin for the treatment of Clostridium difficile infection.
Literature retrieval was accessed through MEDLINE (1966-January 2010) and International Pharmaceutical Abstracts (1970-January 2010) using the terms OPT-80, difimicin, PAR-101, fidaxomicin, tiacumicin, lipiarmycin, and Clostridium difficile. In addition, reference citations from publications identified were reviewed.
All articles published in English that were identified from the data sources were evaluated and pertinent information was included.
Fidaxomicin is an 18-membered macrocyclic antibiotic with activity against gram-positive aerobes and anaerobes, including C. difficile. Microbiologic studies comparing in vitro activity of fidaxomicin with that of metronidazole and vancomycin have shown good activity against all strains of C. difficile tested; however, minimum inhibitory concentrations were consistently lower for fidaxomicin. Studies showed that fidaxomicin lacks activity against gram-negative pathogens, thereby preserving normal gastrointestinal flora. Small pharmacokinetic trials have shown that fidaxomicin administration leads to low concentrations in plasma, high concentrations in stool, and a postantibiotic effect of greater than 24 hours, all of which are potentially advantageous characteristics for treating C. difficile infection. Data from 2 Phase 2A trials and 1 Phase 3 (multicenter, randomized, double-blind) trial suggest that fidaxomicin is effective for the treatment of mild-to-moderate C. difficile infection at a dose of 200 mg orally every 12 hours. Limited early results from the Phase 3 trial showed favorable outcomes for fidaxomicin when compared to oral vancomycin. Overall, fidaxomicin has been well tolerated to date.
The activity of fidaxomicin and limited clinical data suggest that it may have a future role in the treatment of mild-to-moderate C. difficile infection. The complete pharmacokinetic/pharmacodynamic profile, safety, and place in therapy have yet to be determined as trials comparing this agent to vancomycin are forthcoming.
评估 fidaxomicin 治疗艰难梭菌感染的疗效和安全性。
通过 MEDLINE（1966 年 1 月-2010 年 1 月）和国际药学文摘（1970 年 1 月-2010 年 1 月）检索文献，使用 OPT-80、地美环素、PAR-101、fidaxomicin、tiacumicin、脂磷壁酸和艰难梭菌等术语。此外，还查阅了已确定出版物的参考文献。
从资料来源中评估并纳入了所有以英文发表的文章。
fidaxomicin 是一种 18 元大环内酯类抗生素，对革兰阳性需氧菌和厌氧菌具有活性，包括艰难梭菌。比较 fidaxomicin 与甲硝唑和万古霉素体外活性的微生物学研究显示，对所有测试的艰难梭菌菌株均具有良好的活性；然而，最低抑菌浓度始终较低 fidaxomicin。研究表明 fidaxomicin 对革兰氏阴性病原体无活性，从而保留了正常的胃肠道菌群。小型药代动力学试验表明，fidaxomicin 给药后血浆浓度低，粪便浓度高，且具有超过 24 小时的抗生素后效应，这些都是治疗艰难梭菌感染的潜在有利特征。两项 2A 期试验和一项 3 期（多中心、随机、双盲）试验的数据表明，fidaxomicin 以 200mg 口服，每 12 小时一次，治疗轻中度艰难梭菌感染有效。3 期试验的早期有限结果表明，与口服万古霉素相比，fidaxomicin 有良好的疗效。总的来说，迄今为止，fidaxomicin 的耐受性良好。
fidaxomicin 的活性和有限的临床数据表明，它在治疗轻中度艰难梭菌感染方面可能具有未来的作用。由于正在进行比较该药物与万古霉素的试验，因此其完整的药代动力学/药效学特征、安全性和治疗地位尚未确定。
