We systematically reviewed the efficacy and safety of an extended or continuous infusion (EI/CI) versus short-term infusion (STI) of carbapenems in children with severe infections. Databases, including PubMed, Embase, the Cochrane Library, Clinicaltrials.gov, China National Knowledge Infrastructure, WanFang Data, and SinoMed, were systematically searched from their inceptions to 10 August 2020, for all types of studies (such as randomized controlled trials (RCTs), retrospective studies, and pharmacokinetic or population pharmacokinetic (PK/PPK) studies) comparing EI/CI versus STI in children with severe infection. There was no limitation on language, and a manual search was also conducted. The data were screened, evaluated, extracted, and reviewed by two researchers independently. Quantitative (meta-analysis) or qualitative analyses of the included studies were performed. Twenty studies (including two RCTs, one case series, six case reports, and 11 PK/PPK studies) were included in this review (CRD42020162845). The RCTs’ quality evaluation results revealed a risk of selection and concealment bias. Qualitative analysis of RCTs demonstrated that, compared with STI, an EI (3 to 4 h) of meropenem in late-onset neonatal sepsis could improve the clinical effectiveness and microbial clearance rates, and reduce the rates of mortality; however, the differences in the incidence of other adverse events were not statistically significant. Retrospective studies showed that children undergoing an EI of meropenem experienced satisfactory clinical improvement. In addition, the results of the PK/PPK study showed that an EI (3 or 4 h)/CI of carbapenems in severely infected children was associated with a more satisfactory goal achievement rate (probability of target attainment) and a cumulative fraction of response than STI therapy. In summary, the EI/CI of carbapenems in children with severe infection has a relatively sufficient PK or pharmacodynamic (PD) basis and satisfactory efficacy and safety. However, due to the limited quantity and quality of studies, the EI/CI therapy should not be used routinely in severely infected children. This conclusion should be further verified by more high-quality controlled clinical trials or observational studies based on PK/PD theories.

中文翻译：

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严重感染儿童延长或持续输注碳青霉烯类药物：系统评价和综合叙述

我们系统地审查了碳青霉烯类长期或持续输注 (EI/CI) 与短期输注 (STI) 对严重感染儿童的疗效和安全性。包括 PubMed、Embase、Cochrane Library、Clinicaltrials.gov、China National Knowledge Infrastructure、WanFang Data 和 SinoMed 在内的数据库都被系统地检索了从开始到 2020 年 8 月 10 日的所有类型的研究（例如随机对照试验（RCTs） )、回顾性研究和药代动力学或群体药代动力学 (PK/PPK) 研究）在严重感染儿童中比较 EI/CI 与 STI。没有语言限制，还进行了人工搜索。数据由两名研究人员独立筛选、评估、提取和审查。对纳入的研究进行了定量（荟萃分析）或定性分析。本综述纳入了 20 项研究（包括 2 项 RCT、1 项病例系列、6 项病例报告和 11 项 PK/PPK 研究）（CRD42020162845）。RCT 的质量评估结果揭示了选择和隐藏偏倚的风险。RCTs的定性分析表明，与STI相比，美罗培南治疗迟发性新生儿败血症的EI（3～4 h）可提高临床疗效和微生物清除率，降低死亡率；然而，其他不良事件发生率的差异无统计学意义。回顾性研究表明，接受美罗培南 EI 的儿童获得了令人满意的临床改善。此外，PK/PPK 研究的结果表明，与 STI 治疗相比，碳青霉烯类严重感染儿童的 EI（3 或 4 小时）/CI 与更令人满意的目标实现率（目标实现的概率）和累积反应分数相关. 综上所述，重症感染患儿碳青霉烯类药物的EI/CI具有相对充分的PK或药效学（PD）基础，疗效和安全性令人满意。然而，由于研究的数量和质量有限，EI/CI 治疗不应常规用于严重感染的儿童。这一结论还需更多基于PK/PD理论的高质量对照临床试验或观察性研究进一步验证。