Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa; Department of Paediatric Pneumology and Immunology, Charité, Universitätsmedizin Berlin, Germany.
Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa.
Tuberculosis (Edinb). 2015 May;95(3):229-45. doi: 10.1016/j.tube.2015.02.037. Epub 2015 Feb 14.
The fluoroquinolones are key components of current multidrug-resistant tuberculosis (MDR-TB) treatment regimens and are being evaluated in shortened treatment regimens as well as in the prevention of drug-resistant TB. The objective of this review was to identify existing evidence for the use of the fluoroquinolones ofloxacin, levofloxacin and moxifloxacin in the treatment of TB in children. Existing data from in vitro, animal and human studies consistently demonstrate the efficacy of the fluoroquinolones against Mycobacterium tuberculosis, with superiority of levofloxacin and moxifloxacin compared to ofloxacin. In vitro and murine studies demonstrated the potential of moxifloxacin to shorten drug-susceptible TB treatment, but in multiple randomized controlled trials shortened fluoroquinolone-containing regimens have not been non-inferior compared to standard therapy. Resistance occurs frequently via mutations in the gyrA gene, and emerges rapidly depending on the fluoroquinolone concentration, with newer more potent fluoroquinolones less likely to develop resistance. Emerging data from paediatric studies underlines the importance of fluoroquinolones in the treatment of MDR-TB in children. There is a paucity of pharmacokinetic data especially in children <5 years of age and HIV-infected children; existing studies show substantially lower serum concentrations in children compared to adults at currently recommended doses, probably due to faster elimination. This has implications for optimizing paediatric treatment and for the development of resistance. Fluoroquinolone use has been restricted in children due to concerns about drug-induced arthropathy. The available data does not demonstrate any serious arthropathy or other severe toxicity in children. Although there is limited paediatric safety data for the prolonged treatment of MDR-TB, extended administration of fluoroquinolones in adults with MDR-TB does not show serious adverse effects and there is no evidence suggesting less tolerability of fluoroquinolones in children. Additional study of moxifloxacin and levofloxacin for TB treatment and prevention in children is an urgent priority.
氟喹诺酮类药物是当前耐多药结核病（MDR-TB）治疗方案的重要组成部分，它们正在缩短治疗方案以及预防耐药性结核病方面进行评估。本综述的目的是确定现有关于氟喹诺酮类药物氧氟沙星、左氧氟沙星和莫西沙星在儿童结核病治疗中的应用证据。来自体外、动物和人体研究的现有数据一致表明，氟喹诺酮类药物对结核分枝杆菌具有疗效，左氧氟沙星和莫西沙星优于氧氟沙星。体外和鼠类研究表明，莫西沙星有可能缩短对药物敏感的结核病治疗时间，但多项随机对照试验表明，缩短含氟喹诺酮类药物的治疗方案并不优于标准治疗。耐药性通常通过 gyrA 基因突变发生，并且取决于氟喹诺酮类药物的浓度，新型更有效的氟喹诺酮类药物发生耐药性的可能性较小。来自儿科研究的新数据强调了氟喹诺酮类药物在儿童耐多药结核病治疗中的重要性。尤其在 5 岁以下儿童和 HIV 感染儿童中，缺乏药代动力学数据；现有研究表明，与目前推荐剂量的成人相比，儿童的血清浓度明显较低，这可能是由于消除速度更快。这对优化儿科治疗和耐药性发展有影响。由于担心药物引起的关节病，氟喹诺酮类药物在儿童中的使用受到限制。现有数据并未在儿童中显示出任何严重的关节病或其他严重毒性。虽然延长治疗耐多药结核病的儿童安全性数据有限，但在耐多药结核病的成人中延长使用氟喹诺酮类药物不会出现严重不良反应，也没有证据表明儿童对氟喹诺酮类药物的耐受性较低。因此，急需进一步研究莫西沙星和左氧氟沙星在儿童结核病治疗和预防中的应用。
