Frampton James E, Curran Monique P
Adis International Limited, Auckland, New Zealand.
Drugs. 2005;65(18):2623-35; discussion 2636-7. doi: 10.2165/00003495-200565180-00008.
Tigecycline is the first member of a new class of broad-spectrum antibacterials, the glycylcyclines, that has been specifically developed to overcome the two major mechanisms of tetracycline resistance (ribosomal protection and efflux). In vitro, tigecycline was active against a wide range of Gram-positive and -negative aerobic and anaerobic bacteria implicated in complicated skin and skin structure infections (cSSSIs) and complicated intra-abdominal infections (cIAIs). Intravenously administered tigecycline (recommended dosage regimen 100 mg initially, followed by 50 mg every 12 hours for 5-14 days) has been approved by the US FDA for the treatment of cSSSIs and cIAIs. In well designed, pivotal phase III studies, tigecycline monotherapy was noninferior to combination therapy with vancomycin 1 g plus aztreonam 2 g every 12 hours in hospitalised adult patients with cSSSIs (two trials; pooled clinical cure rates, 86.5% vs 88.6%) or broad-spectrum therapy with imipenem/cilastatin 200-500 mg/200-500 mg every 6 hours in hospitalised adult patients with cIAIs (two trials; pooled clinical cure rates, 86.1% vs 86.2%). Tigecycline was generally well tolerated in phase III studies; nausea, vomiting and diarrhoea were the most frequent adverse events in patients treated with tigecycline or an active comparator (vancomycin plus aztreonam or imipenem/cilastatin).
替加环素是新型广谱抗菌药物——甘氨酰环素类中的首个成员,它是专门为克服四环素耐药的两种主要机制(核糖体保护和外排)而研发的。在体外,替加环素对多种革兰氏阳性和阴性需氧及厌氧菌具有活性,这些细菌可导致复杂性皮肤和皮肤结构感染(cSSSI)及复杂性腹腔内感染(cIAI)。静脉注射替加环素(推荐给药方案为初始剂量100mg,随后每12小时50mg,持续5 - 14天)已获美国食品药品监督管理局(US FDA)批准用于治疗cSSSI和cIAI。在精心设计的关键III期研究中,对于患有cSSSI的住院成年患者,替加环素单药治疗不劣于每12小时联合使用1g万古霉素加2g氨曲南的治疗方案(两项试验;合并临床治愈率分别为86.5%和88.6%);对于患有cIAI的住院成年患者,替加环素单药治疗不劣于每6小时使用200 - 500mg亚胺培南/西司他丁的广谱治疗方案(两项试验;合并临床治愈率分别为86.1%和86.2%)。在III期研究中,替加环素总体耐受性良好;恶心、呕吐和腹泻是接受替加环素或活性对照药物(万古霉素加氨曲南或亚胺培南/西司他丁)治疗的患者中最常见的不良事件。