治疗耐多药结核病期间的神经精神毒性和环丝氨酸浓度。
Neuropsychiatric toxicity and cycloserine concentrations during treatment for multidrug-resistant tuberculosis.
机构信息
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Division of Medical Microbiology, University of Cape Town, Cape Town, South Africa.
出版信息
Int J Infect Dis. 2021 Apr;105:688-694. doi: 10.1016/j.ijid.2021.03.001. Epub 2021 Mar 5.
BACKGROUND
Cycloserine, or its structural analogue terizidone, has been associated with neuropsychiatric toxicity (psychosis, depression, and neuropathy). Prospective clinical data on the incidence of and risk factors for neuropsychiatric toxicity in TB patients treated with cycloserine are limited.
METHODS
A prospective evaluation of neuropsychiatric toxicity was performed using validated screening tools in patients with multidrug-resistant tuberculosis treated with terizidone. Cox proportional hazard modelling was performed to explore the effects of clinical variables and measures of cycloserine pharmacokinetics in plasma.
RESULTS
A total 144 participants were recruited: 86 were male and 58 were female; their median age was 35.7 years and 91 (63%) were HIV-infected. Fifty-five (38%) participants developed at least one neuropsychiatric event (30 cases per 100 person-months): 50 (35%) neuropathy, 14 (10%) depression, and 11 (8%) psychosis. Neuropathy was independently associated with cycloserine clearance ((adjusted hazard ratio 0.34 (aHR), P = 0.03)) and high-dose pyridoxine (200 mg vs 150 mg daily, aHR: 2.79, P = 0.01).
CONCLUSIONS
A high incidence of early neuropsychiatric toxicity was observed in this cohort of patients treated with terizidone. Cycloserine clearance and higher doses of pyridoxine are associated with incident or worsening peripheral neuropathy.
背景
环丝氨酸或其结构类似物替利唑酮与神经精神毒性（精神病、抑郁和神经病）有关。关于使用环丝氨酸治疗结核病患者的神经精神毒性的发生率和危险因素的前瞻性临床数据有限。
方法
使用多药耐药结核病患者的替利唑酮治疗的经过验证的筛选工具对神经精神毒性进行前瞻性评估。使用 Cox 比例风险模型探索临床变量和环丝氨酸药代动力学在血浆中的测量值的影响。
结果
共招募了 144 名参与者：86 名男性和 58 名女性；中位年龄为 35.7 岁，91 名（63%）为 HIV 感染者。55 名（38%）参与者至少发生了一次神经精神事件（每 100 人月发生 30 例）：50 例（35%）神经病，14 例（10%）抑郁和 11 例（8%）精神病。神经病与环丝氨酸清除率（调整后的危险比 0.34（aHR），P = 0.03）和高剂量吡哆醇（200 mg 与 150 mg 每日，aHR：2.79，P = 0.01）独立相关。
结论
在接受替利唑酮治疗的患者队列中观察到早期神经精神毒性的发生率很高。环丝氨酸清除率和更高剂量的吡哆醇与周围神经病变的发生或恶化有关。
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