Global Prevalence and Epidemiology of Carbapenem-Resistant Enterobacterales: A Systematic Review

Abstract

Background: Carbapenem-resistant Enterobacterales (CRE) are now an important part of the global antimicrobial resistance problem. They are particularly relevant in hospital practice because the infections they cause are often difficult to treat and therapeutic choices may be limited. However, reported estimates of CRE burden differ considerably between studies. Much of this variation relates to differences in the populations studied, microbiological definitions, surveillance methods, and the denominators used to report resistance. Materials and Methods: We carried out a systematic review of human studies that reported CRE epidemiology using a defined denominator. Studies reporting isolate-based resistance proportions, population- or admission-based incidence, or colonization prevalence were eligible. MEDLINE/PubMed, Embase, Scopus, Web of Science Core Collection, and Global Health were searched from inception to August 13, 2026. Citation searching and targeted surveillance sources were also used. Study selection followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020. Because the studies differed considerably in design and in the epidemiological measures reported, we did not combine the results statistically. Risk of bias was assessed using the Joanna Briggs Institute checklist for prevalence studies, adapted where required for incidence and surveillance studies. Results: Fifteen studies were included. CRE burden varied markedly across regions and healthcare settings, with the highest estimates generally reported in intensive-care and tertiary-care populations and lower estimates in community-based and broader national surveillance. In multinational surveillance, meropenem-non-susceptible Enterobacterales accounted for 3.3% of isolates during 2012–2017 and 5.7% during 2018–2019. Klebsiella pneumoniae was the predominant CRE species in most datasets. Carbapenemase distribution was geographically heterogeneous, with Klebsiella pneumoniae carbapenemases, New Delhi metallo-β-lactamase, and OXA-48-like enzymes predominating in different regions and species. Temporal trends were inconsistent, with increasing resistance in some surveillance systems but declining population-based incidence in the United States. CRE colonization was concentrated among hospitalized and critically ill patients, while direct evidence quantifying progression from colonization to infection was limited. Detailed mortality and other patient-level clinical outcomes were also incompletely reported among the eligible epidemiological studies. The main methodological concerns were representativeness, sampling frame, and surveillance coverage. Conclusion: CRE epidemiology is globally heterogeneous and strongly influenced by healthcare setting, organism, resistance mechanism, and surveillance methodology. Isolate-based resistance proportions, incidence measures, and colonization prevalence are epidemiologically distinct and should not be combined into a single global prevalence estimate. More standardized surveillance, particularly in underrepresented regions and high-risk healthcare settings, is needed to improve comparability and better define the clinical and public-health burden of CRE.