Attributable mortality of infections caused by carbapenem-resistant Enterobacterales: results from a prospective, multinational case-control-control matched cohorts study (EURECA)

María Paniagua-García, Jose M. Bravo-Ferrer, Salvador Pérez-Galera, Tomislav Kostyanev, Marlieke E. A. de Kraker, Jan Feifel, Zaira R. Palacios-Baena, Joost Schotsman, Rafael Cantón, George L. Daikos, Biljana Carevic, Gorana Dragovac, Lionel K. Tan, Lul Raka, Adriana Hristea, Pierluigi Viale, Murat Akova, Ángela Cano, Jose María Reguera, Alessandro BartoloniSimin-Aysel Florescu, Serban Benea, Ljiljana Bukarica, Ángel Asensio, Volkan Korten, Hajo Grundmann, Herman Goossens, Marc J. Bonten, Belén Gutiérrez-Gutiérrez*, Jesús Rodríguez-Baño, The COMBACTE-CARE-EURECA team

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Objectives
To assess the mortality attributable to infections caused by carbapenem-resistant Enterobacterales (CRE) and to investigate the effect of clinical management on differences in observed outcomes in a multinational matched cohort study.

Methods
A prospective matched-cohorts study (NCT02709408) was performed in 50 European hospitals from March 2016 to November 2018. The main outcome was 30-day mortality with an active post-discharge follow-up when applied. The CRE cohort included patients with complicated urinary tract infections, complicated intra-abdominal infections, pneumonia, or bacteraemia from other sources because of CRE. Two control cohorts were selected: patients with infection caused by carbapenem-susceptible Enterobacterales (CSE) and patients without infection. Matching criteria included type of infection for the CSE group, hospital ward of CRE detection, and duration of hospital admission up to CRE detection. Multivariable and stratified Cox regression was applied.

Results

The cohorts included 235 patients with CRE infection, 235 patients with CSE infection, and 705 non-infected patients. The 30-day mortality (95% CI) was 23.8% (18.8-29.6), 10.6% (7.2-15.2), and 8.4% (6.5-10.6), respectively. The difference in 30-day mortality rates between patients with CRE infection when compared with patients with CSE infection was 13.2% (95% CI, 6.3–20.0), (HR, 2.57; 95% CI, 1.55–4.26; p < 0.001), and 15.4% (95% CI, 10.5–20.2) when compared with non-infected patients (HR, 3.85; 95% CI, 2.57–5.77; p < 0.001). The population attributable fraction for 30-day mortality for CRE vs. CSE was 19.28%, and for CRE vs. non-infected patients was 9.61%. After adjustment for baseline variables, the HRs for mortality were 1.87 (95% CI, 0.99–3.50; p 0.06) and 3.65 (95% CI, 2.29–5.82; p < 0.001), respectively. However, when treatment-related time-dependent variables were added, the HR of CRE vs. CSE reduced to 1.44 (95% CI, 0.78–2.67; p 0.24).

Discussion
CRE infections are associated with significant attributable mortality and increased adjusted hazard of mortality when compared with CSE infections or patients without infection. Underlying patient characteristics and a delay in appropriate treatment play an important role in the CRE mortality.
Original languageEnglish
JournalClinical Microbiology and Infection
Volume30
Issue number2
Pages (from-to)223-230
Number of pages8
ISSN1198-743X
DOIs
Publication statusPublished - 2024

Keywords

  • Antimicrobial resistance
  • Carbapenem-resistant Enterobacterales
  • KPC
  • Metallo-β-lactamases
  • Mortality
  • OXA

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