含磷霉素的联合抗菌方案治疗耐碳青霉烯革兰阴性杆菌感染疗效:系统评价与荟萃分析

Effectiveness of fosfomycin-containing combination therapy in the treatment of carbapenem-resistant Gram-negative organism infections:A systematic review and Meta-analysis

目的评价含磷霉素联合治疗碳青霉烯耐药革兰阴性菌(carbapenem-resistant Gram-negative organism,CRO)感染的疗效。探讨含磷霉素联合治疗CRO感染的最佳方案。方法系统检索中国知网、PubMed、Embase、Web of Science、Cochrane Library数据库,收集建库至2023年7月6日公开发表的关于磷霉素治疗CRO感染的相关文献,按照纳入排除标准进行筛选,使用RevMan5.4.1软件进行荟萃分析。主要结局指标包括临床死亡率。使用R软件对含磷霉素的联合治疗方案进行网状Meta分析。使用Cochrane偏差风险评估工具和Newcastle-Ottawa scale量表评估文献质量。本研究已在PROSPERO注册,CRD42022344659。结果最初检索到11806篇文献,其中有16篇、6篇分别纳入死亡率的Meta分析和网状Meta分析。含磷霉素的联合抗菌治疗方案和其他方案治疗CRO感染的总死亡率分别为25%(76/304)和42.63%(350/821),差异有统计学意义[优势比(odds ratio,OR)=0.44;95%CI=0.32-0.62P<0.0001,I^(2)=48%]。在亚组分析中,含磷霉素的联合抗菌治疗方案和其他方案治疗耐碳青霉烯肠杆菌科细菌(carbapenem-resistant Enterobacteriaceae,CRE)感染的总死亡率分别为22.06%(45/204)和35.96%(228/634),差异有统计学意义(OR=0.62,95%CI=0.41~0.95,P=0.03<0.05,I^(2)=0%)。含磷霉素的联合抗菌治疗方案和其他方案治疗耐碳青霉烯鲍曼不动杆菌(carbapenem-resistant Acinetobacter baumannii,CRAB)感染的总死亡率分别为31.87%(29/91)和66.12%(121/183),差异无统计学意义(OR=0.24,95%CI=0.03~1.76,P=0.16>0.05,I^(2)=91%)。在网络荟萃分析中,多利培南+磷霉素治疗CRO感染的死亡率最低。结论含磷霉素的联合治疗方案可显著降低CRO感染患者的死亡率。此外,多利培南加磷霉素可能是最佳的组合方案。

Objective This study evaluated the efficacy of fosfomycin-containing combination therapy for patients with carbapenem-resistant Gram-negative organism(CRO)infections,and explore the best fosfomycincontaining combination therapy regimen for CRO infections.Methods The databases of CNKI,PubMed,Embase,Web of Science,and Cochrane Library were searched systematically,and the related literature on fosfomycin treatment of CRO infections published publicly until July 6,2023,was collected.The literature was screened according to the inclusion and exclusion criteria,and the meta-analysis was performed using RevMan 5.4.1.The primary outcomes included the mortality rate.R software was used for a network meta-analysis of fosfomycin-containing combination therapy.The Cochrane bias risk assessment tool and the Newcastle-Ottawa scale were used to assess the quality of the studies included.Results The initial search yielded 11,806 documents,and 16 studies were finally included for meta-analysis,of which 14 and 6 were used for direct meta-analysis and network meta-analysis respectively.The total mortality rate of CRO infections treated with fosfomycin and other regimens was 25%(76/304)and 42.63%(350/821),respectively,with a statistically significant difference[odds ratio(OR)=0.44;95%CI=0.32~0.62,P<0.0001,I^(2)=48%].In the subgroup analysis,the total mortality rate of carbapenem-resistant Enterobacteriaceae(CRE)infections treated with fosfomycin and other regimens was 22.06%(45/204)and 35.96%(228/634)respectively,with a statistically significant difference(OR=0.62,95%CI=0.41~0.95,P=0.03<0.05,I^(2)=0).The total mortality rate of fosphomycincontaining combined antimicrobial therapy and other regimens in the treatment of carbapenem-resistant Acinetobacter baumannii(CRAB)infections was 31.87%(29/91)and 66.12%(121/183),respectively,with no statistically significant difference(OR=0.24,95%CI=0.03~1.76,P=0.16>0.05,I^(2)=91%).The mortality of CRO infections treated with doripenem and fosfomycin was the lowest.Conclusion The fosfomycin included combination therapy can significantly reduce the mortality of patients with CRO infections.Moreover,doripenem plus fosfomycin may be the best combination regimen.