Therapeutic drug monitoring in the treatment of active tuberculosis
Therapeutic drug monitoring in the treatment of active tuberculosis
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DOI：
10.1155/2011/307150
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发表时间：
2011-07-01
影响因子：
2.2
通讯作者：
Menzies, Dick
中科院分区：
文献类型：
--
作者：
Babalik, Aylin;Mannix, Sharyn;Menzies, Dick
背景：治疗药物监测（TDM）用于优化剂量，使治疗获益最大化，同时使毒性最小化。在治疗活动性结核病（TB），TDM是不是常规的，但低水平的抗结核药物可以与较差的治疗outcomes.METHODS：在一项回顾性病例对照研究中，活动性结核病患者进行TDM被认为是病例，并与对照组谁没有进行TDM，并匹配根据诊断年和直接涂片镜检结果。医疗记录进行了审查，以抽象的人口，临床，影像学和微生物学数据，包括时间，直到涂片和文化conversion.RESULTS：在总数，20例患者中确定了TDM进行，其中17（87%）至少有一个低药物浓度。总体而言，45例患者中有27例（60%）的初始药物浓度较低，导致药物剂量增加。在15次异烟肼测量中有13次（87%）、5次利福平测量中有4次（80%）和12次利福平测量中有8次（67%）发现低药物水平，但在13次吡嗪酰胺测量中只有2次（15%）发现低药物水平。仅在病例中，17例血清药物水平低的患者明显更有可能患有共病，涂片阳性，血清白蛋白水平较低，与所有药物水平均在治疗范围内的3例病例相比，培养转换时间无明显延长。在活动性结核病患者中，特别是在艾滋病毒感染或其他合并症患者中，结核病药物水平经常低于临床可接受水平。TDM对于治疗活动性TB是潜在有用的，但目前未得到充分利用。
BACKGROUND: Therapeutic drug monitoring (TDM) is used to optimize dosing that maximizes therapeutic benefit while minimizing toxicity. In the treatment of active tuberculosis (TB), TDM is not routine, yet low levels of anti-TB drugs can be associated with poorer treatment outcomes.METHODS: In a retrospective case control study, patients with active TB in whom TDM was performed were considered cases and compared with controls who did not undergo TDM, and matched according to year of diagnosis and the results of direct smear microscopy. Medical records were reviewed to abstract demographic, clinical, radiographic and microbiological data including time until smear and culture conversion.RESULTS: In total, 20 patients were identified in whom TDM was performed, of whom 17 (87%) had at least one low drug concentration. Overall, 27 of 45 (60%) initial drug concentrations were low and resulted in an increased drug dosage. Low drug levels were found in 13 of 15 (87%) isoniazid, four of five (80%) rifabutin and eight of 12 (67%) rifampin measurements, but in only two of 13 (15%) pyrazinamide measurements. Within cases only, the 17 patients with low serum drug levels were significantly more likely to have comorbid illnesses, be smear positive, have lower serum albumin levels and had nonsignificantly longer time to culture conversion, compared with the three cases in whom all drug levels were within therapeutic ranges.CONCLUSIONS: TB drug levels were frequently below clinically acceptable levels in patients with active TB, particularly in those with HIV infection or other comorbidities. TDM is potentially useful for the treatment of active TB, but is currently underused.