QT Interval Prolongation with One or More QT-Prolonging Agents Used as Part of a Multidrug Regimen for Rifampicin-Resistant Tuberculosis Treatment: Findings from Two Pediatric Studies.
QT Interval Prolongation with One or More QT-Prolonging Agents Used as Part of a Multidrug Regimen for Rifampicin-Resistant Tuberculosis Treatment: Findings from Two Pediatric Studies.
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DOI：
10.1128/aac.01448-22
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发表时间：
2023-07-18
影响因子：
4.9
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中科院分区：
文献类型：
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利福平耐药结核病 (RR-TB) 需要使用许多可以延长 QT 间期的药物进行治疗；当多种 QT 延长药物一起使用时，这种风险可能会增加。我们评估了接受一种或多种 QT 延长药物治疗的 RR-TB 儿童的 QT 间期延长情况。数据来自南非开普敦的两项前瞻性观察研究。在氯法齐明（CFZ）、左氧氟沙星（LFX）、莫西沙星（MFX）、贝达喹啉（BDQ）和德拉马尼给药前后进行心电图检查。对弗里德里西亚校正 QT (QTcF) 的变化进行了建模。药物和其他协变量效应被量化。总共包括 88 名中位年龄（2.5 至 97.5 范围）为 3.9（0.5 至 15.7）岁的儿童，其中 55 名（62.5%）年龄在 5 岁以下。在 7 例患者就诊中观察到 QTcF 间期 >450ms：治疗方案为 CFZ+MFX (n = 3)、CFZ+BDQ+LFX (n = 2)、单独 CFZ (n = 1) 和单独 MFX (n = 1)。没有 QTcF 间期> 500 毫秒的事件。在多变量分析中，与使用其他基于 MFX 或 LFX 的方案相比，CFZ+MFX 与 QTcF 变化 (P<0.001) 和最大 QTcF (P=0.0166) 增加 13.0 毫秒相关。总之，我们发现接受至少一种 QT 延长药物的 RR-TB 儿童出现 QTcF 间期延长的风险较低。当 MFX 和 CFZ 一起使用时，观察到最大 QTcF 和 ΔQTcF 有更大的增加。如果需要有效治疗 RR-TB，未来对儿童暴露 QTcF 反应进行的研究将有助于确保更高剂量的安全性。
Rifampicin-resistant tuberculosis (RR-TB) involves treatment with many drugs that can prolong the QT interval; this risk may increase when multiple QT-prolonging drugs are used together. We assessed QT interval prolongation in children with RR-TB receiving one or more QT-prolonging drugs. Data were obtained from two prospective observational studies in Cape Town, South Africa. Electrocardiograms were performed before and after drug administration of clofazimine (CFZ), levofloxacin (LFX), moxifloxacin (MFX), bedaquiline (BDQ), and delamanid. The change in Fridericia-corrected QT (QTcF) was modeled. Drug and other covariate effects were quantified. A total of 88 children with a median (2.5th-to-97.5th range) age of 3.9 (0.5 to 15.7) years were included, of whom 55 (62.5%) were under 5 years of age. A QTcF interval of >450 ms was observed in 7 patient-visits: regimens were CFZ+MFX (n = 3), CFZ+BDQ+LFX (n = 2), CFZ alone (n = 1), and MFX alone (n = 1). There were no events with a QTcF interval of >500 ms. In a multivariate analysis, CFZ+MFX was associated with a 13.0-ms increase in change in QTcF (P < 0.001) and in maximum QTcF (P = 0.0166) compared to those when other MFX- or LFX-based regimens were used. In conclusion, we found a low risk of QTcF interval prolongation in children with RR-TB who received at least one QT-prolonging drug. Greater increases in maximum QTcF and ΔQTcF were observed when MFX and CFZ were used together. Future studies characterizing exposure-QTcF responses in children will be helpful to ensure safety with higher doses if required for effective treatment of RR-TB.
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