open access publication

Article, 2024

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

Clinical Microbiology and Infection, ISSN 1198-743X, 1469-0691, Volume 30, 2, Pages 223-230, 10.1016/j.cmi.2023.11.008

Contributors

Paniagua-García, María 0000-0003-3156-7512 [1] [2] Bravo-Ferrer, José María 0000-0002-4638-5001 [2] Pérez-Galera, Salvador Ignacio 0000-0002-3653-2717 [2] [3] Kostyanev, Tomislav S 0000-0002-1259-4876 [4] [5] De Kraker, Marlieke Elizabeth Adriana 0000-0003-0903-8614 [6] Feifel, Jan 0000-0003-3453-9365 [7] Palacios-Baena, Zaira Raquel 0000-0002-1713-6807 [2] [8] Schotsman, Joost [9] Cantón, Rafael 0000-0003-1675-3173 [8] [10] Daikos, George L [11] [12] Carevic, Biljana [13] Dragovac, Gorana [14] Tan, Lionel K [15] Raka, Lul 0000-0002-8710-9791 [16] Hristea, Adriana [17] Viale, Pierluigi [18] Akova, Murat 0000-0002-6904-9473 [19] Cano, Angela [8] [20] Reguera, José María [21] Bartoloni, Alessandro [22] Florescu, Simin-Aysel [23] Benea, Serban [17] Bukarica, Ljiljana [24] Asensio, A Noguerado 0000-0003-2912-8561 [25] Korten, Volkan 0000-0002-9991-814X [26] Grundmann, Hajo 0000-0002-9971-522X [27] Goossens, Herman [5] Bonten, Marc J [7] Gutiérrez-Gutiérrez, Belén 0000-0002-9668-0770 (Corresponding author) [2] [8] Rodríguez-Baño, Jesús 0000-0001-6732-9001 [2] [8] de la Serna, Almudena [3] Monteau, Sophie [3] Palomo, Virginia 0000-0003-3200-9598 [3] Soriano, Elena [3] Gutierrez, David [3] Moreno, Elisa [3] Sojo-Dorado, Jesús [3] Morales, Isabel [3] Maldonado, Natalia [3] De Santis, Lucia Valiente [21] Ciezar, Antonio Plata [21] Mesa, Juan Diego Ruiz [21] Diaz, Beatriz Sobrino 0000-0002-7241-4208 [21] Gómez, Ignacio Márquez [21] Camacho, Ines Perez [21] Cano, Angela [28] Frutos-Adame, Azahara [28] Guzmán-Puche, Julia 0000-0003-2199-7949 [28] Gracia-Ahufinger, Irene 0000-0001-7714-6620 [28] Pérez-Nadales, Elena 0000-0002-6796-1813 [28] Torre-Gimenez, Julian [28] Pyrpasopoulou, Athina 0000-0002-6906-2504 [29] Iosifidis, Elias 0000-0001-9881-451X [29] Chorafa, Elsa [29] Radovanovic, Ivana [13] Petrovic, Sladjana [13] Cvetkovi, Slavica [13] Melentijevic, Srdjan-Sanja [30] Bicmen, Can [31] Senol, Gunes 0000-0002-1027-7578 [31] Tubau, Fe 0000-0002-6416-6451 [32] Càmara, Jordi 0000-0002-0817-0931 [32] Gumucio, Victor Daniel [32] Bassoulis, Dimitris [11] Deliolanis, John [11] Pitiriga, Vassiliki Ch 0000-0002-1951-8489 [33] Triarides, Nikolaos A [33] Argiti, Efstathia [33] Legakis, Nikolaos J [34] Margarita, Kyriakidou [34] Gijón-Cordero, Desirée [10] Ruiz-Garbajosa, Patricia [10] Rossolini, Gian Maria [22] Nica, Maria [35] Talapan, Daniela [17] Medic, Deana D [14] Prijić, Sanja Maričić [14] Caballero, Mireia Cantero [25] Ramírez, Lina M Parra [26] Bilgin, Hüseyin [36] Dalekos, George Nikolaos 0000-0001-7075-8464 [36] Stefos, Aggelos 0000-0002-4954-8857 [36] Spyridis, Nikolaos [37] Michos, Athanasios G 0000-0003-1745-1118 [12] De Rosa, Francesco Giuseppe [38] Cavallo, Rossana [38] Petrosillo, Nicola [39] Dicaro, Antonio [39] Landini, Maria Paola [40] Degli Atti, Marta Luisa Ciofi 0000-0001-6492-4497 [41] Masanovic, Mileva [42] Matkovic, Dusan [42] Tsiodras, Sotirios 0000-0002-0463-4321 [12] Blasi, Francesco [43] Di pasquale, Marta [43] Viscoli, Claudio [44] Vata, Andrei [45] Dorneanu, Olivia [45] Kapisyzi, Perlat Qazim [46] Vince, Adriana [47] Tsigou, Evdoxia [48] Maltezos, Efstratios S 0000-0002-5827-2661 [49] Komnos, Apostolos 0000-0002-7225-3213 [36] Gogos, Charalampos [50] Franzetti, Fabio [51] De Rosa, Francesco Giuseppe Antonelli, Massimo [52] Lupse, Mihaela Sorina 0000-0003-4010-2901 [53] Corneci, Dan E 0000-0002-1170-0614 [54] Tomescu, Dana [55] Georgescu, Anca [56] Bukarica, Ljiljana Mitrović, Goran [57] Krstić, Nataša Lukić [57] Kurti, Arsim [58] Reuter, Sandra [27] Díaz-Pollán, Beatriz 0000-0002-7241-4208 [59] Sabater, Julia Origüen [60] Muñoz, Patricia [61] Azap, Alpay 0000-0001-5035-055X [62] ancak, Banu [19] Sahin, Arife [19] Akalin, H Erdal 0000-0001-7530-1279 [63]

Affiliations

  1. [1] Hospital Universitario Virgen del Rocío
    2. [NORA names: Spain; Europe, EU; OECD];
  2. [2] Unidad de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena and Departamento de Medicina, Universidad de Sevilla/Instituto de Biomedicina de Sevilla/CSIC, Seville, Spain
    3. [NORA names: Spain; Europe, EU; OECD];
  3. [3] Hospital Universitario Virgen Macarena
    4. [NORA names: Spain; Europe, EU; OECD];
  4. [4] Technical University of Denmark
    5. [NORA names: DTU Technical University of Denmark; University; Denmark; Europe, EU; Nordic; OECD];
  5. [5] University of Antwerp
    6. [NORA names: Belgium; Europe, EU; OECD];

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.

Keywords

CRE detection, Cox regression, EURECA, Enterobacterales, European hospitals, HR, adjusted hazard, adjustment, associated with significant attributable mortality, attributable fraction, attributable mortality, bacteraemia, baseline, baseline variables, carbapenem-resistant Enterobacterales, carbapenem-resistant Enterobacterales infections, carbapenem-susceptible Enterobacterales, characteristics, clinical management, cohort, cohort study, complicated intra-abdominal infections, complicated urinary tract infections, control, control cohort, criteria, delay, detection, differences, duration, effect, effectiveness of clinical management, follow-up, fraction, group, hazard, hospital, hospital wards, increased adjusted hazard, infection, intra-abdominal infections, management, matched cohort study, matched-cohort study, matching, matching criterion, mortality, mortality attributable to infection, mortality of infections, mortality rate, non-infected patients, outcomes, patient characteristics, patients, pneumonia, population, population attributable fraction, post-discharge follow-up, rate, regression, results, source, stratified Cox regression, study, tract infections, treatment, urinary tract infection, variables

Funders

  • Government of Catalonia
  • Instituto de Salud Carlos III
  • Comunidad de Madrid

Data Provider: Digital Science

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