Effectiveness of fosfomycin-containing combination therapy in the treatment of carbapenem-resistant Gram-negative organism infections:A systematic review and Meta-analysis
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 fosfomycin-containing 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,I2=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,I2=0).The total mortality rate of fosphomycin-containing 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,I2=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.
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