Health Outcomes Attributable to Carbapenemase-Producing Enterobacteriaceae Infections: A Systematic Review

Dalton R Budhram1, Stephen Mac2,3, Samir N Patel4,5, Joanna M Bielecki3, Beate Sander3,2,4,6
1Department of Medicine, Queen’s University, Kingston, ON, Canada. 2Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada. 3Toronto Health Economics and Technology Assessment (THETA) Collaborative, University Health Network, Toronto, ON, Canada. 4Public Health Ontario, Toronto, ON, Canada. 5Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. 6Institute for Clinical Evaluative Sciences, Toronto, ON, Canada


Objective: Carbapenemase-producing Enterobacteriaceae (CPE) are a subgroup of carbapenem-resistant bacteria that pose a significant global health threat. We conducted a systematic literature review on the health-related quality of life (HRQoL), 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 four electronic databases: Medline, Embase, CINAHL and the Cochrane Library between January 2008 and May 2018 for concepts related to: CPE, quality-of-life, complications, and mortality. We included primary studies with a carbapenem-susceptible control group, conducted in Organization for Economic Co-operation and Development countries. We excluded studies that were not published in English, used an inappropriate control, or reported inappropriate outcomes. Quality appraisal was completed using Joanna Briggs Institute checklists. We qualitatively summarized the most frequently reported sequelae and conducted a meta-analysis. Results: We identified 8,671 studies of which 17 met the eligibility criteria for inclusion into this review. All studies reported health outcomes, none reported HRQoL. Most studies were conducted in teaching or university-affiliated hospitals (76%), from Europe (65%), and used case-control designs (53%). Mortality was the most commonly reported consequence of CPE-infections, with in-hospital mortality as the most often reported outcome (62%). Our meta-analysis (n=5 studies) estimated a risk difference of the in-hospital mortality rate of 0.25 (95% CI, 0.17 – 0.32). Duration of antibiotic therapy (range, 4-29.7 days vs. 1-23.6 days) and length of hospital stay (range, 21-87 days vs. 15-43 days) were relatively higher for CPE-infected patients compared to carbapenem susceptible patients. Overall, most studies (82%) met over 80% of their respective quality appraisal criteria. Conclusions: Health outcome studies associated with CPE infection are focused on short-term (e.g. in-hospital) outcomes; long-term sequelae and quality-of-life are not well studied. Future opportunities exist for longer follow-up to assess the clinical outlook for CPE infections.