Pediatric tuberculosis is a neglected disease that is receiving more attention lately. Some studies found that serum levels of first line antituberculosis drugs do not reach reference concentrations in children. However, these reference ranges were validated in an adult sample. Thus, we do not know if subtherapeutic concentrations of antitubercular agents in children is associated with negative outcomes. Objective: To estimate the association between subtherapeutic concentrations of first-line antitubercular drugs with clinical outcomes of treatment. Methods: We propose to do a systematic review and meta-analysis. In order to do so, we will perform an electronic search in Medline, SCOPUS, Web of Science. There will be no restriction of language nor date of publication. First, we will screen titles and abstracts; then we will screen through the full text of the article. Both phases will be done by 2 independent authors. Data extraction will be performed using a data abstraction form by two independent authors. The quality of the studies will be checked with standardized tools according to the design of the study, and will also be performed by duplicate. We will present the main characteristics of each included study through tables. The heterogeneity between studies will be assessed through the I2 statistic. If appropriate, we will use the random-effects model to calculate the pooled estimate. We will evaluate the publication bias through visual inspection of the funnel plot and Egger test. Pre-arranged subgroup and sensitivity analysis will be performed. Results: We will publish the results of this systematic review in a peer-reviewed journal. Conclusions: This systematic review will provide up-to-date evidence regarding serum concentration in pediatric patients and its association with outcomes. With the analysis we plan, we will offer important recommendations regarding the dosage of the first line antitubercular agents in children, and the modifications that may be needed.

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小儿患者一线抗结核药物亚治疗浓度及其与结核病治疗结果的关系：系统评价和荟萃分析的方案

小儿结核病是一种被忽视的疾病，近来受到越来越多的关注。一些研究发现，一线抗结核药物的血清水平未达到儿童的参考浓度。但是，这些参考范围已在成人样本中得到验证。因此，我们不知道儿童抗结核药的亚治疗浓度是否与阴性结果相关。目的：评估一线抗结核药物亚治疗浓度与临床疗效之间的关系。方法：我们建议进行系统的回顾和荟萃分析。为此，我们将在Medline，SCOPUS，Web of Science中进行电子搜索。语言和发布日期均不受限制。首先，我们将筛选标题和摘要；然后我们将浏览文章全文。这两个阶段将由2位独立作者完成。数据提取将由两位独立作者使用数据抽象形式进行。研究的质量将根据研究的设计使用标准化工具进行检查，并且还将重复进行。我们将通过表格介绍每个纳入研究的主要特征。研究之间的异质性将通过I2统计数据进行评估。如果合适，我们将使用随机效应模型来计算合并的估计。我们将通过目视检查漏斗图和Egger检验来评估发布偏差。将进行预先安排的子组和敏感性分析。结果：我们将在同行评审的期刊上发表这项系统评价的结果。结论：这项系统的综述将提供有关儿科患者血清浓度及其与预后的关系的最新证据。通过我们计划的分析，我们将针对儿童一线抗结核药的剂量以及可能需要的修改提供重要的建议。