近日，南非斯泰伦博斯大学Anneke C. Hesseling团队研究了左氧氟沙星预防治疗暴露于耐多药结核病儿童。2024年12月19日，《新英格兰医学杂志》发表了这一成果。

在全球范围内，约有200万名15岁以下的儿童感染了耐多药结核分枝杆菌，每年约有3万人患上耐多药结核病。但缺乏对暴露于耐多药结核病者进行结核病预防治疗的随机对照试验的证据。

研究组在南非进行了一项基于社区、多地点、双盲、集群随机、安慰剂对照试验，评估了左氧氟沙星作为预防性治疗与细菌学确诊的耐多药肺结核成年人有家庭接触儿童的有效性和安全性。5岁以下的儿童有资格纳入，无论干扰素-γ释放试验结果或人类免疫缺陷病毒（HIV）状态如何；5至17岁的儿童如果干扰素-γ分泌试验呈阳性或HIV感染，则有资格纳入。

家庭被随机分配到一个试验方案，家庭中的儿童每天接受一次左氧氟沙星或安慰剂治疗，持续24周。主要疗效终点是随机分组后第48周的结核病发病率，包括结核病死亡。主要安全终点是治疗期间至少可能与试验方案相关的任何3级或更高级别的不良事件。

在来自497个家庭的922名参与者中，453名被分配接受左氧氟沙星治疗，469名被分配服用安慰剂；91.0%的参与者年龄小于5岁。每个试验组中86%的参与者接受了至少80%的左氧氟沙星或安慰剂指定剂量。到第48周，左氧氟沙星组有5名参与者（1.1%）出现结核病，安慰剂组有12名参与者（2.6%）出现结核病（风险比为0.44；95%置信区间[CI]为0.15至1.25）。敏感性分析的结果与初步分析的结果一致。左氧氟沙星组的4名参与者和安慰剂组的8名参与者在治疗期间发生了3级或更高级别的不良事件，这些不良事件被认为至少可能与试验方案有关（风险比，0.52；95%置信区间，0.16至1.71）。左氧氟沙星组有1名儿童出现2级肌腱炎。

研究结果表明，虽然在家庭接触耐多药结核病的儿童中，左氧氟沙星预防性治疗导致的结核病发病率低于安慰剂，但差异并不显著。

附：英文原文

Title: Levofloxacin Preventive Treatment in Children Exposed to MDR Tuberculosis

Author: Anneke C. Hesseling, Susan E. Purchase, Neil A. Martinson, Lee Fairlie, H. Simon Schaaf, Joanna Brigden, Suzanne Staples, Diana M. Gibb, Anthony Garcia-Prats, Francesca Conradie, Charlotte McGowan, Charlotte Layton, Elize Batist, Anne-Marie Demers, Samukelisiwe Nyamathe, Lisa Frigati, Rebecca Turner, Trinh Duong, James A. Seddon

Issue&Volume: 2024-12-19

Abstract:

BACKGROUND

Worldwide, approximately 2 million children younger than 15 years of age are infected with multidrug-resistant (MDR) Mycobacterium tuberculosis, with MDR tuberculosis developing in approximately 30,000 annually. Evidence from randomized, controlled trials on tuberculosis preventive treatment in persons exposed to MDR tuberculosis is lacking.

METHODS

In this community-based, multisite, double-blind, cluster-randomized, placebo-controlled trial in South Africa, we assessed the efficacy and safety of levofloxacin as preventive treatment in children with household exposure to an adult with bacteriologically confirmed MDR pulmonary tuberculosis. Children younger than 5 years of age were eligible for inclusion regardless of interferon-γ release assay result or human immunodeficiency virus (HIV) status, and children 5 to 17 years of age were eligible if they had a positive interferon-γ release assay or HIV infection. Households were randomly assigned to a trial regimen, and children in the household received levofloxacin or placebo once daily for 24 weeks. The primary efficacy end point was incident tuberculosis, which included death from tuberculosis, by week 48 after randomization. The primary safety end point was any adverse event of grade 3 or higher during the treatment period that was at least possibly related to the trial regimen.

RESULTS

Of 922 participants from 497 households, 453 were assigned to receive levofloxacin and 469 to placebo; 91.0% of the participants were younger than 5 years of age. At least 80% of the assigned doses of levofloxacin or placebo were received by 86% of the participants in each trial group. By week 48, tuberculosis had developed in 5 participants (1.1%) in the levofloxacin group and in 12 participants (2.6%) in the placebo group (hazard ratio, 0.44; 95% confidence interval [CI], 0.15 to 1.25). The results of sensitivity analyses were consistent with those of the primary analysis. Grade 3 or higher adverse events during the treatment period that were considered to be at least possibly related to the trial regimen occurred in 4 participants in the levofloxacin group and in 8 participants in the placebo group (hazard ratio, 0.52; 95% CI, 0.16 to 1.71). Grade 2 tendonitis occurred in 1 child in the levofloxacin group.

CONCLUSIONS

Although preventive treatment with levofloxacin led to a lower incidence of tuberculosis than placebo among children with household exposure to MDR tuberculosis, the difference was not significant.

DOI: NJ202412193912408

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2314318