Jacobs M R
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
Drugs. 1995;49 Suppl 2:67-75. doi: 10.2165/00003495-199500492-00011.
The fluoroquinolones have been shown to be highly active in vitro against many mycobacterial species, including most strains of Mycobacterium tuberculosis and M. fortuitum, and some strains of M. kansasii, M. avium-intracellulare (MAI) complex and M. leprae. Ciprofloxacin, ofloxacin and sparfloxacin are the best studied of this class of drugs to date, and they are among the most active of these against M. tuberculosis and other mycobacteria. The use of ofloxacin in the treatment of patients with multidrug-resistant pulmonary tuberculosis has resulted in the selection of quinolone-resistant mutants in a few patients. Many strains of MAI, however, are resistant to fluoroquinolones, and structure-activity relationship studies have been undertaken to identify the moieties associated with activity and inactivity. The most important features determining activity against MAI were found to be a cyclopropyl ring at the N1 position, fluorine atoms at positions C6 and C8, and a C7 heterocyclic substituent. On the basis of these structural requirements, a series of compounds were tested, and many did indeed show good activity against MAI in vitro. Application of these data to macrophage and animal models is in progress. Clinical evaluation of some of these new fluoroquinolones is also being undertaken in multidrug-resistant tuberculosis and MAI and M. leprae infections. Although the development of resistance and the influence of host factors may limit their use, they have considerable potential if prudently used.
氟喹诺酮类药物已被证明在体外对许多分枝杆菌具有高度活性，包括大多数结核分枝杆菌和偶然分枝杆菌菌株，以及堪萨斯分枝杆菌、鸟分枝杆菌-胞内分枝杆菌（MAI）复合体和麻风分枝杆菌的一些菌株。环丙沙星、氧氟沙星和司帕沙星是迄今为止对这类药物研究最多的，它们也是对结核分枝杆菌和其他分枝杆菌活性最强的药物之一。在耐多药肺结核患者的治疗中使用氧氟沙星，已导致少数患者中出现了对喹诺酮耐药的突变体。然而，许多MAI菌株对氟喹诺酮类药物耐药，因此已经开展了构效关系研究，以确定与活性和非活性相关的部分。发现决定对MAI活性的最重要特征是N1位的环丙基环、C6和C8位的氟原子以及C7杂环取代基。基于这些结构要求，测试了一系列化合物，许多化合物在体外确实显示出对MAI的良好活性。这些数据在巨噬细胞和动物模型中的应用正在进行中。一些新型氟喹诺酮类药物也正在耐多药结核病以及MAI和麻风分枝杆菌感染中进行临床评估。尽管耐药性的产生和宿主因素的影响可能会限制它们的使用，但如果谨慎使用，它们具有相当大的潜力。
