Linezolid toxicity in patients with drug-resistant tuberculosis: a prospective cohort study.
Linezolid toxicity in patients with drug-resistant tuberculosis: a prospective cohort study.
复制标题
DOI：
10.1093/jac/dkac019
复制
发表时间：
2022-03-31
期刊：
影响因子：
--
通讯作者：
Maartens G
中科院分区：
文献类型：
--
作者：
Wasserman S;Brust JCM;Abdelwahab MT;Little F;Denti P;Wiesner L;Gandhi NR;Meintjes G;Maartens G
推荐使用利奈唑胺治疗耐药结核病。不良事件是处方者关注的问题，但尚未在标准剂量下进行系统研究，利奈唑胺暴露与临床毒性之间的关系尚未完全阐明。我们进行了一项观察性队列研究，以描述南非利福平耐药结核病患者中利奈唑胺毒性的发生率和决定因素，并确定毒性的药物暴露阈值。利奈唑胺暴露量是根据群体药代动力学模型估算的。使用混合效应模型来分析毒性结果。 151 名参与者（其中 63% 为 HIV 阳性）被纳入研究并进行了中位 86 周的随访。 32 名 (21%) 参与者因毒性而永久停用利奈唑胺。 21 名 (14%) 参与者发生了 3 级或 4 级利奈唑胺相关不良事件。平均血红蛋白浓度随着治疗时间的延长而增加（每周 0.03 g/dL；95% CI，0.02 至 0.03）。利奈唑胺谷浓度、男性性别和年龄（但不是 HIV 阳性）与血红蛋白下降 > 2 g/dL 独立相关。利奈唑胺谷浓度为 2.5 mg/L 或更高可实现描述血红蛋白变化和治疗引起的贫血的最佳模型性能（调整后比值比 2.9；95% CI，1.3 至 6.8）。线粒体DNA中的单核苷酸多态性2706A>G和3010G>A与利奈唑胺毒性无关。永久停用利奈唑胺很常见，但含利奈唑胺的治疗与毒性指标的平均改善相关。 HIV 合并感染与利奈唑胺毒性并不独立相关。利奈唑胺谷浓度 2.5 mg/L 应作为治疗药物监测的目标进行评估。
Linezolid is recommended for treating drug-resistant tuberculosis. Adverse events are a concern to prescribers but have not been systematically studied at the standard dose, and the relationship between linezolid exposure and clinical toxicity is not completely elucidated. We conducted an observational cohort study to describe the incidence and determinants of linezolid toxicity, and to determine a drug exposure threshold for toxicity, among patients with rifampicin-resistant tuberculosis in South Africa. Linezolid exposures were estimated from a population pharmacokinetic model. Mixed-effects modelling was used to analyse toxicity outcomes. 151 participants, 63% HIV-positive, were enrolled and followed for a median of 86 weeks. Linezolid was permanently discontinued for toxicity in 32 (21%) participants. Grade 3 or 4 linezolid-associated adverse events occurred in 21 (14%) participants. Mean haemoglobin concentrations increased with time on treatment (0.03 g/dL per week; 95% CI, 0.02 to 0.03). Linezolid trough concentration, male sex, and age (but not HIV-positivity) were independently associated with a decrease in haemoglobin > 2 g/dL. Trough linezolid concentration of 2.5 mg/L or higher resulted in optimal model performance to describe changing haemoglobin and treatment-emergent anaemia (adjusted odds ratio 2.9; 95% CI, 1.3 to 6.8). Single nucleotide polymorphisms 2706A>G and 3010G>A in mitochondrial DNA were not associated with linezolid toxicity. Permanent discontinuation of linezolid was common, but linezolid-containing therapy was associated with average improvement in toxicity measures. HIV co-infection was not independently associated with linezolid toxicity. Linezolid trough concentration of 2.5 mg/L should be evaluated as a target for therapeutic drug monitoring.
登录
查看更多内容
DOI：
10.1016/j.jctube.2020.100201
发表时间：
2021-03
影响因子：
2
作者：
McDowell A;Haas M;Seaworth B;Wilson JW;Patrawalla A;Haley C;Lauzardo M;de Bruyn M;Goswami ND
通讯作者：
Goswami ND
影响因子：
158.5
作者：
Conradie, Francesca;Diacon, Andreas H.;Spigelman, Melvin
通讯作者：
Spigelman, Melvin
影响因子：
11.8
作者：
Minchella, Peter A.;Donkor, Simon;McDermid, Joann M.
通讯作者：
McDermid, Joann M.
DOI：
10.1016/s1055-3290(98)80048-4
发表时间：
1998-07-01
期刊：
The Journal of the Association of Nurses in AIDS Care : JANAC
影响因子：
--
作者：
McArthur, J H
通讯作者：
McArthur, J H
DOI：
10.1007/s10096-019-03754-1
发表时间：
2020-03-01
影响因子：
4.5
作者：
Cazavet, Julien;Bounes, Fanny Vardon;Georges, Bernard
通讯作者：
Georges, Bernard