Impact of carbapenem resistance on mortality in patients infected with Enterobacteriaceae: a systematic review and meta-analysis

OBJECTIVES: To provide a comprehensive assessment of the impact of carbapenem resistance on mortality among patients infected with Enterobacteriaceae and to explore the source of heterogeneity across studies. DESIGN: This systematic review was conducted following the guidelines of Cochrane Guidance and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. DATA SOURCES: We conducted a systematic literature search of the PubMed, Embase, Web of Science and Cochrane Library databases to identify relevant studies published between 1 January 1994 and 30 August 2020. ELIGIBILITY CRITERIA: We included primary observational studies published in English that reported the mortality outcomes for hospitalised patients with confirmed infections due to carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem-susceptible Enterobacteriaceae (CSE). Studies with no comparison group or with a comparison group of patients infected with unconfirmed CSE were excluded. DATA EXTRACTION AND SYNTHESIS: Data extraction and assessment of risk bias were conducted independently by two reviewers. The pooled relative risk and risk difference were calculated as effect measures with 95% CIs using a random effects model. The heterogeneity across studies was assessed by Q-statistic and I(2) measures. RESULTS: Of 10 304 studies initially identified, 50 studies were included in the meta-analyses. The results of the meta-analyses showed that carbapenem resistance has a significant positive effect on the probability of death for patients infected with Enterobacteriaceae for any type of mortality outcome. The results of the stratified analysis and meta-regression suggested that the effect of carbapenem resistance on the risk of death varied by infection type, sample size and year of publication. CONCLUSIONS: Our results suggested that patients with CRE infection still face a greater risk of death than patients with CSE infection do, and an urgent need to develop new antibiotics and appropriate treatments to reduce the risk of death. PROSPERO REGISTRATION NUMBER: CRD42020176808.