McKeage Kate, Keating Gillian M
Wolters Kluwer Health, Adis, Auckland, New Zealand.
Drugs. 2008;68(18):2633-44. doi: 10.2165/0003495-200868180-00008.
Tigecycline is a first-in-class glycylcycline, broad-spectrum, intravenous antibacterial developed to overcome the two major mechanisms of tetracycline resistance (ribosomal protection and efflux). The drug has been in use since 2005 for complicated intra-abdominal infections, and complicated skin and soft tissue structure infections, but is currently being assessed in the US for community-acquired pneumonia (CAP) in adults. In vitro, tigecycline had good activity against a range of Gram-positive, Gram-negative and atypical community-acquired respiratory tract pathogens implicated in CAP. Compared with other antibacterials, tigecycline has a prolonged post-antibiotic effect against key bacteria and a long serum elimination half-life in humans. The drug effectively penetrates lung tissue. The combined results of two well designed, phase III studies demonstrated that tigecycline 100 mg initially, followed by 50 mg every 12 hours for 7-14 days was not inferior to recommended dosages of levofloxacin in the treatment of hospitalized patients with CAP. Clinical cure rates were 89.7% versus 86.3% in the clinically evaluable population and 81.0% versus 79.7% in the clinical modified intent-to-treat population. Tigecycline was generally well tolerated in patients with CAP.
替加环素是首个新型甘氨酰环素类、广谱、静脉用抗菌药物,其研发旨在克服四环素耐药的两种主要机制(核糖体保护和外排)。该药物自2005年起用于治疗复杂性腹腔内感染以及复杂性皮肤和软组织感染,目前正在美国进行针对成人社区获得性肺炎(CAP)的评估。在体外实验中,替加环素对一系列与CAP相关的革兰氏阳性、革兰氏阴性及非典型社区获得性呼吸道病原体具有良好活性。与其他抗菌药物相比,替加环素对关键细菌具有较长的抗生素后效应,且在人体内血清消除半衰期较长。该药物能有效穿透肺组织。两项精心设计的III期研究的综合结果表明,对于住院的CAP患者,初始剂量为100mg替加环素,随后每12小时50mg,持续7 - 14天,在治疗效果上不劣于推荐剂量的左氧氟沙星。在临床可评估人群中,临床治愈率分别为89.7%和86.3%;在临床改良意向性治疗人群中,临床治愈率分别为81.0%和79.7%。CAP患者对替加环素总体耐受性良好。