The Natural History of Carbapenemase-Producing Enterobacterales: Progression From Carriage of Various Carbapenemases to Bloodstream Infection

Background Little is known about the risk of progression from carbapenemase-producing Enterobacterales (CPE) carriage to CPE bloodstream infection (BSI) outside of high-risk settings. We aimed to determine the incidence of CPE BSI among CPE carriers and to assess whether the incidence differs by carbapenemase, species, and setting.Methods We conducted a nationwide population-based retrospective cohort study using national databases. The cohort consisted of all patients in Israel with CPE detected by screening from 1 January 2020 to 10 October 2022. We calculated the cumulative incidence of CPE BSI within 1 year among CPE carriers. We used a competing-risks model with BSI as the outcome and death as the competing risk.Results The study included 6828 CPE carriers. The cumulative incidence of CPE BSI was 2.4% (95% confidence interval [CI], 2.1-2.8). Compared with Klebsiella pneumoniae carbapenemase (KPC), the subhazard of BSI was lower for New Delhi metallo-beta-lactamase (NDM) (adjusted subhazard ratio [aSHR], 0.72; 95% CI, .49-1.05) and oxacillinase-48-like (OXA-48-like) (aSHR, 0.60; 95% CI, .32-1.12) but these differences did not reach statistical significance. Compared with K. pneumoniae, the subhazard of BSI was lower for carriers of carbapenemase-producing Escherichia coli (aSHR, 0.33; 95% CI, .21-.52). The subhazard of BSI was higher among patients with CPE carriage first detected in intensive care units (aSHR, 2.10; 95% CI, 1.27-3.49) or oncology/hematology wards (aSHR, 3.95; 95% CI, 2.51-6.22) compared with medical wards.Conclusions The risk of CPE BSI among CPE carriers is lower than previously reported in studies that focused on high-risk patients and settings. The risk of BSI differs significantly by bacterial species and setting, but not by carbapenemase. In this population-based study, the 1-year cumulative incidence of bloodstream infection among carriers of carbapenemase-producing Enterobacterales was 2.4%. The risk of bloodstream infection did not differ significantly by carbapenemase type. Graphical Abstract This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/the-natural-history-of-carbapenemase-producing-enterobacterales-progression-from-carriage-of-various-carbapenemases-to-bloodstream-infection-13ed2007-b0c6-4f55-8ddc-aee03327b53e