Outcomes and use of therapeutic drug monitoring in multidrug-resistant tuberculosis patients treated in virginia, 2009-2014.
Outcomes and use of therapeutic drug monitoring in multidrug-resistant tuberculosis patients treated in virginia, 2009-2014.
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DOI：
10.4046/trd.2015.78.2.78
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发表时间：
2015-04
影响因子：
2.9
通讯作者：
Houpt ER
中科院分区：
文献类型：
--
作者：
Heysell SK;Moore JL;Peloquin CA;Ashkin D;Houpt ER
治疗耐多药结核病（MDR-TB）二线药物的治疗药物监测（TDM）报告仍然有限。对2009-2014年弗吉尼亚州结核病（TB）登记处的一个回顾性队列进行了分析，以了解TDM在MDR-TB中的使用情况。将估计峰值（Cmax）时测量的药物浓度与预期范围进行比较。在10例MDR-TB患者中，8例（80%）至少接受了一种药物（最多6种药物）的TDM。二线药物测试环丝氨酸在7名患者（平均C2 hr，16.6±10.2 µg/mL; 4例[57%]低于预期范围）; 5例患者中，（平均C2小时，3.2±1.5 µg/mL;低于1 [20%]）;卷曲霉素在5个（平均C2 hr，21.5±14.0 µg/mL;低于3 [60%]）; 5个样本中的对氨基水杨酸（平均C6 h，65.0±29.1 µg/mL;均在范围内或以上）;利奈唑胺，在3个（平均C2小时，11.4±4.1 µg/mL，低于1 [33%]）;阿米卡星（平均C2小时，35.3±3.7 µg/mL;低于1 [50%]）;乙硫异烟胺（C2小时，1.49 µg/mL，在预期范围内）。2例患者死亡：1例38岁女性，患有人类免疫缺陷病毒/获得性免疫缺陷综合征和结核性脑膜炎，无TDM; 1例76岁男性，患有氟喹诺酮耐药（广泛耐药前）肺结核，利奈唑胺和卷曲霉素浓度较低。个体药代动力学变异性很常见。一种更加标准化的耐多药结核病TDM方法可能会限制过度检测，并最大限度地提高治疗效果。
Reports of therapeutic drug monitoring (TDM) for second-line medications to treat multidrug-resistant tuberculosis (MDR-TB) remain limited. A retrospective cohort from the Virginia state tuberculosis (TB) registry, 2009-2014, was analyzed for TDM usage in MDR-TB. Drug concentrations, measured at time of estimated peak (Cmax), were compared to expected ranges. Of 10 patients with MDR-TB, 8 (80%) had TDM for at least one drug (maximum 6 drugs). Second-line drugs tested were cycloserine in seven patients (mean C2hr, 16.6±10.2 µg/mL; 4 [57%] below expected range); moxifloxacin in five (mean C2hr, 3.2±1.5 µg/mL; 1 [20%] below); capreomycin in five (mean C2hr, 21.5±14.0 µg/mL; 3 [60%] below); para-aminosalicylic acid in five (mean C6hr, 65.0±29.1 µg/mL; all within or above); linezolid in three (mean C2hr, 11.4±4.1 µg/mL, 1 [33%] below); amikacin in two (mean C2hr, 35.3±3.7 µg/mL; 1 [50%] below); ethionamide in one (C2hr, 1.49 µg/mL, within expected). Two patients died: a 38-year-old woman with human immunodeficiency virus/acquired immune deficiency syndrome and TB meningitis without TDM, and a 76-year-old man with fluoroquinolone-resistant (pre-extensively drug-resistant) pulmonary TB and low linezolid and capreomycin concentrations. Individual pharmacokinetic variability was common. A more standardized approach to TDM for MDR-TB may limit over-testing and maximize therapeutic gain.