Health outcomes attributable to carbapenemase-producing Enterobacteriaceae infections: A systematic review and meta-analysis

Background: Carbapenemase-producing Enterobacteriaceae (CPE) pose a significant global health threat. Objective: To conduct a systematic review of health outcomes and long-term sequelae attributable to CPE infection. Methods: We followed PRISMA reporting guidelines and published our review protocol on PROSPERO (CRD42018097357). We searched Medline, Embase, CINAHL and the Cochrane Library. We included primary studies with a carbapenem-susceptible control group in high-income countries, published in English. Quality appraisal was completed using Joanna Briggs Institute checklists. We qualitatively summarized frequently reported outcomes and conducted a meta-analysis. Results: Our systematic review identified 8,671 studies; 17 met the eligibility criteria for inclusion. All studies reported health outcomes; none reported health-related quality-of-life. Most studies were from Europe (65%), were conducted in teaching or university-affiliated hospitals (76%), and used case-control designs (53%). Mortality was the most commonly reported consequence of CPE-infections; in-hospital mortality was most often reported (62%). Our meta-analysis (n = 5 studies) estimated an absolute risk difference (ARD) for in-hospital bloodstream infection mortality of 0.25 (95% confidence interval [CI], 0.17-0.32). Duration of antibiotic therapy (range, 4-29.7 vs 1-23.6 days) and length of hospital stay (range, 21-87 vs 15-43 days) were relatively higher for CPE-infected patients than for patients infected with carbapenem-susceptible pathogens. Most studies (82%) met >80% of their respective quality appraisal criteria. Conclusions: The risk of in-hospital mortality due to CPE bloodstream infection is considerably greater than carbapenem-susceptible bloodstream infection (ARD, 0.25; 95% CI, 0.17-0.32). Health outcome studies associated with CPE infection are focused on short-term (eg, in-hospital) outcomes; long-term sequelae and quality-of-life are not well studied.