Effectiveness and Cardiac Safety of Bedaquiline-Based Therapy for Drug-Resistant Tuberculosis: A Prospective Cohort Study.
Effectiveness and Cardiac Safety of Bedaquiline-Based Therapy for Drug-Resistant Tuberculosis: A Prospective Cohort Study.
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DOI：
10.1093/cid/ciab335
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发表时间：
2021-12-06
期刊：
影响因子：
--
通讯作者：
Meintjes G
中科院分区：
文献类型：
--
作者：
Brust JCM;Gandhi NR;Wasserman S;Maartens G;Omar SV;Ismail NA;Campbell A;Joseph L;Hahn A;Allana S;Hernandez-Romieu AC;Zhang C;Mlisana K;Viljoen CA;Zalta B;Ebrahim I;Franczek M;Master I;Ramangoaela L;Te Riele J;Meintjes G
贝达奎林改善了利福平耐药(RR)结核病患者的治疗结果，但延长了QT间期，并带有美国食品和药物管理局的黑盒警告。世界卫生组织建议所有RR结核病患者接受含有贝达奎林的方案，但证明其心脏安全性的3期临床试验尚未发表。我们对南非3个省的RR结核病患者进行了一项观察性队列研究，这些患者接受了含有贝达奎林的治疗方案。我们进行了严格的心脏监测，包括在贝达奎林治疗期间的4个时间点采集三份心电图。对参与者进行跟踪，直到治疗结束或24个月。结果包括最终的结核病治疗结果和QT间期延长(QT延长)，其定义为经Fridericia方法(QTcF)和GT；500ms校正的任何QT间期或与基线(ΔQTcF)和Gt；60ms的绝对变化。我们招募了195名符合条件的参与者，其中40%患有广泛耐药结核病。大多数参与者(97%)同时接受氯法齐明治疗。在参与者中，74%的人治愈或成功完成了治疗，结果并不因人类免疫缺陷病毒状态而异。在贝达奎林治疗期间，QTcF持续增加，从基线到6个月的平均增加(标准差)为23.7ms。4名参与者经历了QTcF>；500ms，19名参与者经历了ΔQTcF&Gt；60ms。年龄越大与QT延长独立相关。同时接受洛匹那韦-利托那韦治疗的受试者QT延长既不常见也不严重。严重的QT延长并不常见，不需要贝达奎林或氯法齐明的永久停药。对于老年患者，密切监测QT间期可能是可取的。经Fridericia方法(QTcF)校正的QT间期严重延长在同时使用贝达奎林和氯法齐明的方案治疗多药耐药或广泛耐药结核病的参与者中并不常见。在人类免疫缺陷病毒流行率较高的情况下，结果是有利的。同时接受Lopinavir-ritonavir治疗的参与者没有出现进一步的QTcF延长。
Bedaquiline improves treatment outcomes in patients with rifampin-resistant (RR) tuberculosis but prolongs the QT interval and carries a black-box warning from the US Food and Drug Administration. The World Health Organization recommends that all patients with RR tuberculosis receive a regimen containing bedaquiline, yet a phase 3 clinical trial demonstrating its cardiac safety has not been published. We conducted an observational cohort study of patients with RR tuberculosis from 3 provinces in South Africa who received regimens containing bedaquiline. We performed rigorous cardiac monitoring, which included obtaining electrocardiograms in triplicate at 4 time points during bedaquiline therapy. Participants were followed up until the end of therapy or 24 months. Outcomes included final tuberculosis treatment outcome and QT interval prolongation (QT prolongation), defined as any QT interval corrected by the Fridericia method (QTcF) >500 ms or an absolute change from baseline (ΔQTcF) >60 ms. We enrolled 195 eligible participants, of whom 40% had extensively drug-resistant tuberculosis. Most participants (97%) received concurrent clofazimine. Of the participants, 74% were cured or successfully completed treatment, and outcomes did not differ by human immunodeficiency virus status. QTcF continued to increase throughout bedaquiline therapy, with a mean increase (standard deviation) of 23.7 (22.7) ms from baseline to month 6. Four participants experienced a QTcF >500 ms and 19 experienced a ΔQTcF >60 ms. Older age was independently associated with QT prolongation. QT prolongation was neither more common nor more severe in participants receiving concurrent lopinavir-ritonavir. Severe QT prolongation was uncommon and did not require permanent discontinuation of either bedaquiline or clofazimine. Close monitoring of the QT interval may be advisable in older patients. Severe prolongation of the QT interval corrected by the Fridericia method (QTcF) was uncommon among participants treated for multidrug-resistant or extensively drug-resistant tuberculosis with a regimen containing both bedaquiline and clofazimine. Outcomes were favorable in this setting with high human immunodeficiency virus prevalence. Participants receiving concurrent lopinavir-ritonavir did not experience further QTcF prolongation.
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影响因子：
24.3
作者：
Pym, Alexander S.;Diacon, Andreas H.;Dannemann, Brian
通讯作者：
Dannemann, Brian
影响因子：
9.4
作者：
Kaniga, Kone;Aono, Akio;Omar, Shaheed, V
通讯作者：
Omar, Shaheed, V
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：
11.1
作者：
Ismail NA;Omar SV;Joseph L;Govender N;Blows L;Ismail F;Koornhof H;Dreyer AW;Kaniga K;Ndjeka N
通讯作者：
Ndjeka N
影响因子：
76.2
作者：
Schnippel, Kathryn;Ndjeka, Norbert;Conradie, Francesca
通讯作者：
Conradie, Francesca