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

Clin Infect Dis. 2024 Jul 19;79(1):22-29. doi: 10.1093/cid/ciae110.

Abstract

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-β-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.

Keywords: antibiotic resistance; bloodstream infection; carbapenem-resistant Enterobacterales; carbapenemase; epidemiology.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bacteremia* / epidemiology
  • Bacteremia* / microbiology
  • Bacterial Proteins* / metabolism
  • Carbapenem-Resistant Enterobacteriaceae / isolation & purification
  • Carrier State* / epidemiology
  • Carrier State* / microbiology
  • Enterobacteriaceae / drug effects
  • Enterobacteriaceae / enzymology
  • Enterobacteriaceae / isolation & purification
  • Enterobacteriaceae Infections* / epidemiology
  • Enterobacteriaceae Infections* / microbiology
  • Female
  • Humans
  • Incidence
  • Israel / epidemiology
  • Male
  • Middle Aged
  • Retrospective Studies
  • beta-Lactamases* / metabolism

Substances

  • beta-Lactamases
  • carbapenemase
  • Bacterial Proteins