The role of fluoroquinolones in tuberculosis today
The role of fluoroquinolones in tuberculosis today
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DOI：
10.2165/00003495-200161010-00002
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发表时间：
2001-01-01
期刊：
影响因子：
11.5
通讯作者：
Berning, SE
中科院分区：
文献类型：
--
作者：
Berning, SE
结核病是一个日益严重的国际卫生问题；它是当今世界主要的传染病死亡原因。氟喹诺酮类药物是最新一类药物，为抗击这种疾病带来了希望。环丙沙星、氧氟沙星、左氧氟沙星和司帕沙星是目前最常用的抗结核分枝杆菌药物，体外最低抑菌浓度(MIC)为0.1~4微克/毫升。结核分枝杆菌对氟喹诺酮类药物可自发耐药，也可获得性耐药，尤其是当这些药物使用不当时。氟喹诺酮类药物在结核病中表现出交叉耐药。氟喹诺酮类药物为结核病的治疗提供了有利的药代动力学特征。大多数表现出极好的口服生物利用度和达到最大(峰值)血药浓度远高于最低抑菌浓度。它们也广泛分布，包括细胞内。氟喹诺酮类药物在肾脏和/或肝脏被清除，其血清半衰期各不相同。氟喹诺酮类药物在峰值浓度(C-max)与最低抑菌浓度(MIC)比值最大时最有效。环丙沙星和氧氟沙星等氟喹诺酮类药物曾用于预防结核病的方案，但与吡嗪酰胺联合使用时耐受性较差。临床结核病的治疗方案中使用氟喹诺酮类药物取得了良好的反应。然而，它们不能被认为是异烟肼或利福平(利福平)的同等替代品，应该与至少两种其他抗结核药物一起使用。对氟喹诺酮类药物的治疗监测有助于确保实现最大C-max与MIC比率，特别是在有吸收不良风险的患者中，如感染艾滋病毒的患者。大多数氟喹诺酮类药物每日一次的高剂量在治疗结核病中变得越来越普遍。长期使用氟喹诺酮类药物治疗结核病通常耐受性良好，但据报道，一般使用氟喹诺酮类药物会产生罕见的严重不良反应。在结核病治疗中，最常见的药物与氟喹诺酮类药物的相互作用包括与多价阳离子相关的吸收不良相互作用以及细胞色素P450与环丙沙星的相互作用。据报道，环丝氨酸可增加中枢神经系统损害的风险。当使用氟喹诺酮类药物治疗结核病时，应仔细考虑个体的敏感性模式、药代动力学和毒副作用。结核病专家的帮助也可能是有必要的。氟喹诺酮类药物在治疗结核病中的确切作用仍有待确定。
Tuberculosis is a growing international health concern; it is the leading infectious cause of death in the world today. The fluoroquinolones are the most recent class of drugs offering hope in the fight against this disease. Ciprofloxacin, ofloxacin, levofloxacin and sparfloxacin an currently the most commonly used agents used against Mycobacterium tuberculosis (TB), with in vitro minimum inhibitory concentrations (MICs) of 0.1 to 4 mcg/ml. Resistance in TB to fluoroquinolones may occur spontaneously or may be acquired, especially when these agents are used inappropriately. Cross-resistance among the fluoroquinolones has been shown in TB.The fluoroquinolones offer a favourable pharmacokinetic profile for the treatment of TB. Most demonstrate excellent oral bioavailability and achieve maximum (peak) serum concentrations well above the MIC. They are also distributed widely, including intracellularly. The fluoroquinolones are cleared renally and/or hepatically, with varying serum half-lives. Fluoroquinolones are most effective when the peak concentration (C-max) to MIC ratio is maximised.Fluoroquinolones such as ciprofloxacin and ofloxacin have been used in regimens for the prevention of TB, but have been poorly tolerated when used in combination with pyrazinamide. Favourable responses with fluoroquinolones in regimens used in the treatment of clinical TB disease have been seen. They, however, are not to be considered as equal replacements for isoniazid or rifampicin (rifampin) and should be used with at least 2 other antituberculous agents. Therapeutic drug monitoring of fluoroquinolones is beneficial in assuring that maximum C-max to MIC ratios are being achieved, especially in patients at risk for malabsorption, such as those infected with HIV. Higher, once-daily doses of most fluoroquinolones are becoming more common in treating TB.Fluoroquinolones are generally well tolerated with long term use in treating TB, but rare, serious adverse effects have been reported with general fluoroquinolone use. The most common drug interactions with fluoroquinolones in TB therapy include the malabsorption interactions associated with multivalent cations and cytochrome P450 interactions with ciprofloxacin. An increased risk of central nervous system effects with concomitant cycloserine has been reported and seen clinically.When using fluoroquinolones to treat TB, careful consideration of individual susceptibility patterns, pharmacokinetic and toxicity profiles should be taken. The aid of a TB expert may also be warranted. The exact role of the fluoroquinolones in treating TB remains to be determined.