Kimerling M E, Phillips P, Patterson P, Hall M, Robinson C A, Dunlap N E
Division of International Health, School of Public Health, University of Alabama at Birmingham, 35294-0008, USA.
Chest. 1998 May;113(5):1178-83. doi: 10.1378/chest.113.5.1178.
Despite the use of directly observed therapy (DOT) by tuberculosis control programs, patient treatment failure, relapse, and acquired drug resistance remain problematic in a small number. We investigated serum drug levels in non-HIV-infected tuberculosis patients who were receiving DOT by the health department and did not respond to treatment as expected.
The indications for checking levels were as follows: (1) slow clinical response or failure to convert the sputum culture within 12 weeks; (2) treatment failure, early disease relapse < 13 months since being declared cured; (3) relapse, late disease reactivation > or = 13 months since being declared cured; and (4) acquired drug resistance while receiving DOT. Baseline characteristics of control subjects who responded to therapy as expected were compared. Venous blood for analysis was obtained at 2 h after directly observed ingestion and measured by high-performance liquid chromatography.
Twenty-four patients receiving daily or twice-weekly standard therapy with isoniazid (INH, 300 or 900 mg) and rifampin (RMP, 600 mg) were identified; 22 had drug levels evaluated at 2 h. For INH, 15 of 22 patients (68%) had levels less than the reported target range. For RMP, 14 of 22 patients (64%) had low levels. Among the 14 patients receiving INH, 900 mg, and RMP, 600 mg, 4 (29%) had very low levels of both. Use of a combination INH/RMP tablet was associated with lower INH levels (p=0.04); however, RMP levels were higher (p<0.02). Alcohol use was associated with significantly higher RMP (p<0.01) serum concentrations.
Important questions remain concerning the utility and timing of serum drug measurements. However, if a patient is not responding to therapy as expected and one is assured that the Mycobacterium tuberculosis organism is susceptible to the drugs given and that the patient is taking the medication as prescribed, drug level monitoring should be considered.
尽管结核病控制项目采用了直接观察治疗（DOT），但仍有少数患者治疗失败、复发以及出现获得性耐药问题。我们调查了由卫生部门实施DOT且治疗效果未达预期的非HIV感染结核病患者的血清药物水平。
检查血清药物水平的指征如下：（1）临床反应缓慢或在12周内痰培养未转阴；（2）治疗失败，自宣告治愈后13个月内疾病早期复发；（3）复发，自宣告治愈后13个月及以上疾病晚期再活动；（4）接受DOT时出现获得性耐药。比较了预期治疗有反应的对照受试者的基线特征。在直接观察服药后2小时采集静脉血用于分析，并通过高效液相色谱法进行测定。
确定了24例接受异烟肼（INH，300或900mg）和利福平（RMP，600mg）每日或每周两次标准治疗的患者；其中22例在2小时时评估了药物水平。对于INH，22例患者中有15例（68%）的水平低于报告的目标范围。对于RMP，22例患者中有14例（64%）水平较低。在接受900mg INH和600mg RMP的14例患者中，4例（29%）两种药物水平都非常低。使用INH/RMP复方片剂与较低的INH水平相关（p=0.04）；然而，RMP水平较高（p<0.02）。饮酒与显著更高的RMP血清浓度相关（p<0.01）。
关于血清药物测量的效用和时机仍存在重要问题。然而，如果患者治疗效果未达预期，且确定结核分枝杆菌对所给药物敏感且患者按规定服药，则应考虑进行药物水平监测。
