美罗培南用于新生儿感染安全性的Meta分析

甄路路 刘璐 刘畅 闫美兴

中圖分类号 R969.3;R722.13 文献标志码 A 文章编号 1001-0408（2021）18-2260-07

DOI 10.6039/j.issn.1001-0408.2021.18.14

摘 要 目的：系统评价美罗培南用于新生儿感染的安全性，旨在为该药在新生儿人群中的安全使用提供循证参考。方法：计算机检索PubMed、Embase、Cochrane图书馆、ISI Web of Science、国际卫生技术评估机构网络、中国期刊全文数据库、万方数据、中国生物医学文献服务系统、中文科技期刊全文数据库等，收集美罗培南或美罗培南联合其他药物（试验组）对比可替代美罗培南的同类药物（对照组）用于新生儿感染的随机对照试验（RCT），检索时限为建库起至2021年5月1日。筛选文献并提取资料后，采用Cochrane系统评价员手册5.1.0推荐的偏倚风险评估工具对纳入文献质量进行评价，采用 RevMan 5.3软件进行 Meta分析。结果：共纳入25项RCT，共计2 090例患儿。Meta分析结果显示，试验组患儿的整体不良反应发生率显著低于对照组[RR=0.53，95%CI（0.44，0.65），P<0.000 01]。亚组分析结果显示，试验组患儿的整体不良反应发生率均显著低于对照组使用头孢他啶[RR=0.55，95%CI（0.41，0.74），P<0.000 1]、替加环素[RR=0.37，95%CI（0.23，0.59），P<0.000 1]、头孢曲松[RR=0.53，95%CI（0.35，0.80），P=0.003]的患儿;试验组新生儿化脓性脑膜炎[RR=0.63，95%CI（0.44，0.92），P=0.02]、新生儿重症多重耐药菌感染[RR=0.37，95%CI（0.25，0.55），P<0.000 01]、新生儿重症细菌感染[RR=0.67，95%CI（0.48，0.94），P=0.02]患儿的整体不良反应发生率均显著低于对照组。试验组患儿的皮疹、胃肠道反应、血红蛋白下降等具体不良反应发生率均显著低于对照组（P<0.05）;而两组患儿的转氨酶升高、继发真菌感染、肾损伤等具体不良反应发生率比较，差异均无统计学意义（P>0.05）。发表偏倚分析结果显示，以整体不良反应发生率为指标时，本研究存在一定程度的发表偏倚;以具体不良反应发生率为指标时，本研究存在发表偏倚的可能性较小。结论：美罗培南用于新生儿感染的安全性较好，特别是用于新生儿化脓性脑膜炎、新生儿重症多重耐药菌感染、新生儿重症细菌感染时的安全性优于头孢他啶、替加环素、头孢曲松等抗菌药物。

关键词 美罗培南;新生儿;感染;安全性;Meta分析

Meta-analysis of the Safety of Meropenem for Neonatal Infection

ZHEN Lulu1，LIU Lu2，LIU Chang2，YAN Meixing2（1. School of Medicine and Pharmacy， Ocean University of China， Shandong Qingdao 266003， China; 2. Dept. of Pharmacy， Qingdao Womens and Childrens Hospital， Shandong Qingdao 266000， China）

ABSTRACT   OBJECTIVE： To systematically evaluate the safety of meropenem for neonatal infection， and to provide evidence-based reference for safe use of it in the neonatal population. METHODS： Retrieved from PubMed， Embase， Cochrane Library， ISI Web of Science， International Health Technology Assessment Network Website， China Journal Full-text Database， Wanfang Database， CBM， Chinese Sci-tech Periodical Full-text Database， randomized controlled trials （RCTs） about meropenem or meropenem combined other drugs （trial group） versus the similar drugs that could replace meropenem （control group） for neonatal infection were collected during the inception to May 1st， 2021. After literature screening and data extraction， the quality of included literatures were evaluated with Cochrane systematically evaluator manual 5.1.0. Meta-analysis was conducted with RevMan 5.3 software. RESULTS： A total of 25 RCTs were included， involving 2 090 children. Results of Meta-analysis showed that the incidence of overall ADR in trial group was significantly lower than control group [RR=0.53，95%CI（0.44，0.65）， P<0.000 01]. Results of subgroup analysis showed that the incidence of overall ADR in trial group was significantly lower than control group receiving ceftazidime [RR=0.55， 95%CI（0.41，0.74）， P<0.000 1]， tigecycline [RR=0.37， 95%CI（0.23，0.59）， P<0.000 1]， ceftriaxone [RR=0.53， 95%CI（0.35，0.80）， P=0.003]. The incidence of overall ADR in trial group with neonatal purulent meningitis [RR=0.63，95%CI（0.44，0.92）， P=0.02]， severe neonatal multidrug-resistant bacterial infection [RR=0.37， 95%CI（0.25，0.55）， P<0.000 01]， neonatal severe bacterial infection [RR=0.67， 95%CI （0.48， 0.94）， P=0.02] were significantly lower than control group. The incidence of specific ADR such as rash， gastrointestinal reaction， hemoglobin reduction in trial group were significantly lower than control group （P<0.05）. There was no statistical significance in the incidence of specific ADR between 2 groups， such as elevated transaminase， secondary fungal infection and renal injury （P>0.05）. Results of bias analysis showed that when the incidence of overall ADR was used as index， there was a certain degree of publication bias in this study， when the incidence of specific ADR was used as index， there was less possibility of publication bias in this study. CONCLUSIONS： Meropenem is safe in the treatment of neonatal infection， especially in the treatment of neonatal purulent meningitis， severe neonatal multidrug-resistant bacterial infection and neonatal severe bacterial infection， it is superior to ceftazidime， tigecycline， ceftriaxone and other antibacterial drugs in safety.

KEYWORDS   Meropenem; Newborn; Infection; Safety; Meta-analysis

美罗培南为人工合成的广谱碳青霉烯类抗菌药物，可通过抑制细菌细胞壁的合成而产生抗菌作用，且易穿透大多数革兰氏阳性菌和阴性菌的细胞壁，适用于成人和儿童由单一或多种对美罗培南敏感的细菌所引起的感染[1]。……