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.

Automated summary

The study found that carbapenem resistance has a significant positive effect on the probability of death for patients infected with Enterobacteriaceae. Stratified analysis and meta-regression results suggested that the effect of carbapenem resistance on the risk of death varies by infection type, sample size, and year of publication.