Moadebi Susanne, Harder Curtis K, Fitzgerald Mark J, Elwood Kevin R, Marra Fawziah
Vaccine and Pharmacy Services, BC Centre for Disease Control, 655 West 12th Avenue, Vancouver, British Columbia, Canada.
Drugs. 2007;67(14):2077-99. doi: 10.2165/00003495-200767140-00007.
Tuberculosis (TB) continues to be a significant problem globally. Treatment includes a multiple drug regimen with isoniazid, rifampicin (rifampin), pyrazinamide and ethambutol. Often, one of these medications needs to be replaced as a result of adverse events or because Mycobacterium tuberculosis develops resistance against one these first-line agents. Fluoroquinolones, particularly the newer ones, possess good in vitro (levofloxacin, gatifloxacin, moxifloxacin) and in vivo (gatifloxacin and moxifloxacin) bactericidal activity against M. tuberculosis, making them attractive agents for the treatment of pulmonary TB. All relevant clinical trials, cohort studies and case reports investigating the clinical efficacy and tolerability of fluoroquinolones when used for the treatment of pulmonary TB were evaluated for this review. Specifically, efficacy and safety in the following indications were investigated: (i) first-line treatment of drug-sensitive pulmonary TB; (ii) first-line treatment for multi-drug resistant (MDR) TB; and (iii) treatment of patients with drug intolerance. Twenty-seven articles met our inclusion criteria; nine articles presented data from randomised, controlled or cohort studies. Seven studies used fluoroquinolones as first-line agents in drug-sensitive TB (1469 patients), 15 studies used fluoroquinolones to treat MDR-TB (1025 patients) and six studies (951 patients) investigated the use of fluoroquinolones in patients intolerant to other TB medications. In patients with susceptible M. tuberculosis strains, substitution with a fluoroquinolone did not have an effect on cure or radiological improvement at 8 weeks or failure at 12 months. Substitution of older fluoroquinolones into a regimen, especially ciprofloxacin, resulted in a higher rate of relapse and a longer time to sputum-culture conversions. The use of fluoroquinolones in patients with MDR-TB is supported by some trials where others show a lack of improvement in efficacy of a regimen. Our review of the literature does not support the use of older fluoroquinolones, especially ciprofloxacin, as substitute agents for drug-sensitive or drug-resistant TB. However, newer fluoroquinolones, such as moxifloxacin, may be a reasonable alternative based on results from one large clinical trial. Fluoroquinolones have an important role as substitute agents for those who are intolerant of first-line TB agents.
结核病在全球范围内仍然是一个重大问题。治疗方案包括使用异烟肼、利福平、吡嗪酰胺和乙胺丁醇的多药联合疗法。通常，由于出现不良事件或结核分枝杆菌对这些一线药物产生耐药性，其中一种药物需要更换。氟喹诺酮类药物，尤其是较新的品种，对结核分枝杆菌具有良好的体外（左氧氟沙星、加替沙星、莫西沙星）和体内（加替沙星和莫西沙星）杀菌活性，使其成为治疗肺结核的有吸引力的药物。本综述评估了所有调查氟喹诺酮类药物用于治疗肺结核时的临床疗效和耐受性的相关临床试验、队列研究和病例报告。具体而言，研究了以下适应症的疗效和安全性：（i）药物敏感型肺结核的一线治疗；（ii）耐多药肺结核的一线治疗；（iii）对药物不耐受患者的治疗。27篇文章符合我们的纳入标准；9篇文章提供了随机、对照或队列研究的数据。7项研究将氟喹诺酮类药物用作药物敏感型肺结核的一线药物（1469例患者），15项研究使用氟喹诺酮类药物治疗耐多药肺结核（1025例患者），6项研究（951例患者）调查了氟喹诺酮类药物在对其他抗结核药物不耐受患者中的使用情况。在结核分枝杆菌菌株敏感的患者中，用氟喹诺酮类药物替代对8周时的治愈或影像学改善以及12个月时的治疗失败没有影响。将较老的氟喹诺酮类药物，尤其是环丙沙星，替换到治疗方案中会导致更高的复发率和更长的痰培养转阴时间。一些试验支持在耐多药肺结核患者中使用氟喹诺酮类药物，而其他试验则显示治疗方案的疗效没有改善。我们对文献的综述不支持使用较老的氟喹诺酮类药物，尤其是环丙沙星，作为药物敏感型或耐药型肺结核的替代药物。然而，基于一项大型临床试验的结果，较新的氟喹诺酮类药物，如莫西沙星，可能是一个合理的选择。氟喹诺酮类药物作为对一线抗结核药物不耐受者的替代药物具有重要作用。
