雾化阿米卡星辅助治疗多重耐药革兰阴性菌肺炎疗效与安全性的Meta分析

Meta analysis of efficacy and safety of amikacin nebulization as adjuvant therapy for multi-drug resistant Gram-negative bacteria pneumonia

目的系统评价雾化阿米卡星(amikacin nebulization,AN)辅助治疗多重耐药革兰阴性菌肺炎(multi-drug resistant gram-negativebacteriapneumonia,MDR-GNBP)的疗效与安全性。方法计算机检索数据库,按照纳入与排除标准纳入关于AN辅助治疗MDR-GNBP的随机对照试验(randomized controlled trials,RCT),并采用Review Manager 5.4和Stata SE 12.0软件进行Meta分析。结果纳入9篇(10RCT研究)关于AN辅助治疗MDR-GNBP的文献,包含1302例患者。Meta分析的结果显示:在有效性方面,AN可提高MDR-GNBP患者的临床治愈率[RR=1.27(95%CI=1.03~1.58),P=0.03],尤其是呼吸机相关性肺炎患者的临床治愈率[RR=1.75(95%CI=1.21~2.53),P=0.003]。另外,AN可提高MDR-GNBP患者的微生物清除率[RR=1.34(95%CI=1.09~1.66),P=0.005],缩短ICU停留时间[WMD=-2.23(95%CI=-3.79~-0.66),P=0.005],但不能降低全因死亡率[RR=1.01(95%CI=0.78~1.31),P=0.96]和肺炎相关死亡率[RR=1.09(95%CI=0.77~1.53),P=0.64]。在安全性方面,AN不增加MDR-GNBP患者的不良反应发生率[RR=1.01(95%CI=0.95~1.09),P=0.68]、肾损伤发生率[RR=0.74(95%CI=0.52~1.05),P=0.09],但会增加呼吸道痉挛的发生率[RR=2.50(95%CI=1.12~5.56),P=0.02]。结论AN辅助治疗MDR-GNBP有一定优势,可作为一种新的治疗选择,但仍需大规模、多中心的RCT来验证。

Objective This study aimed to evaluate the efficacy and safety of amikacin nebulization(AN)as adjuvant therapy for multi-drug-resistant Gram-negative bacteria pneumonia(MDR-GNBP).Methods The published randomized controlled trials(RCTs)of AN as adjuvant therapy for MDR-GNBP were searched by extracting data from clinical studies that met the inclusion and exclusion criteria,which were analyzed by Review Manager 5.4 and Stata SE 12.0 software.Results A total of 9 articles(10 RCTs)involving 1302 patients were included.The results of the Meta-analysis showed that in terms of effectiveness,AN adjuvant therapy could improve the clinical cure rate of MDR-GNBP patients[RR=1.27(95%CI=1.03~1.58),P=0.03],especially in ventilator-associated pneumonia patients[RR=1.75(95%CI=1.21~2.53),P=0.003].In addition,it could also improve the patient's microbial clearance rate[RR=1.34(95%CI=1.09~1.66),P=0.005],shorten the ICU stay time[WMD=-2.23(95%CI=-3.79~0.66),P=0.005],but could not reduce the all-cause mortality rate[RR=1.01(95%CI=0.78~1.31),P=0.96]or pneumonia-related mortality rate[RR=1.09(95%CI=0.77~1.53),P=0.64].In terms of safety,AN did not increase the incidence rate of adverse reactions in patients[RR=1.01(95%CI=0.95~1.09),P=0.68],or the incidence rate of kidney injury[RR=0.74(95%CI=0.52~1.05),P=0.09],but it did increase the incidence rate of respiratory spasm[RR=2.50(95%CI=1.12~5.56),P=0.02].Conclusion AN as adjuvant therapy for MDR-GNBP had certain advantages and could be used as a new treatment option,but it still required a large-scale and multicenter RCT to verify.