Attributable mortality of infections caused by carbapenem-resistant Enterobacterales: results from a prospective, multinational case-control-control matched cohorts study (EURECA)
Authors: 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 Bartoloni, Simin-Aysel Florescu, Serban Benea, Ljiljana Bukarica, Ángel Asensio, Volkan Korten, Hajo Grundmann, Herman Goossens, Marc J. Bonten, Belén Gutiérrez-Gutiérrez, Jesús Rodríguez-Baño, Almudena de la Serna, Sophie Monteau, Virginia Palomo, Elena Soriano, David Gutierrez, Elisa Moreno, Jesus Sojo-Dorado, Isabel Morales, Natalia Maldonado, Lucia Valiente de Santis, Antonio Plata Ciezar, Juan Diego Ruiz Mesa, Beatriz Sobrino Diaz, Ignacio Marquez Gomez, Ines Perez Camacho, Angela Cano, Azahara Frutos-Adame, Julia Guzman-Puche, Irene Gracia-Ahufinger, Elena Perez-Nadales, Julian Torre-Gimenez, Athina Pyrpasopoulou, Elias Iosifidis, Elsa Chorafa, Ivana Radovanovic, Sladjana Petrovic, Slavica Cvetkovi, Srdjan-Sanja Melentijevic, Can Bicmen, Gunes Senol, Fe Tubau, Jordi Camara, Victor Daniel Gumucio, Dimitris Bassoulis, John Deliolanis, Vassiliki Ch. Pitiriga, Nikolaos Triarides, Efstathia Argiti, Nikolaos J. Legakis, Kyriakidou Margarita, Desirée Gijón-Cordero, Patricia Ruiz-Garbajosa, Gian Maria Rossolini, Maria Nica, Daniela Talapan, Deana Medić, Sanja Maričić Prijić, Mireia Cantero Caballero, Lina M Parra Ramírez, Hüseyin Bilgin, George N. Dalekos, Aggelos Stefos, Nikolaos Spyridis, Athanasios Michos, Francesco Giuseppe De Rosa, Rossana Cavallo, Nicola Petrosillo, Antonio Dicaro, Maria Paola Landini, Marta Luisa Ciofi degli Atti, Mileva Masanovic, Dusan Matkovic, Sotirios Tsiodras, Francesco Blasi, Marta Di pasquale, Claudio Viscoli, Andrei Vata, Olivia Dorneanu, Perlat Kapisyzi, Adriana Vince, Evdoxia Tsigou, Efstratios Maltezos, Apostolos Komnos, Charalampos Gogos, Fabio Franzetti, Francesco Giuseppe De Rosa, Massimo Antonelli, Mihaela Lupse, Dan Corneci, Dana Tomescu, Anca Georgescu, Ljiljana Bukarica, Goran Mitrović, Nataša Lukić Krstić, Arsim Kurti, Sandra Reuter, Beatriz Díaz-Pollán, Julia Origüen Sabater, Patricia Muñoz, Alpay Azap, Banu ancak, Arife Sahin, Halis Akalin
Journal: Clinical Microbiology and Infection (2024)

<h2>Abstract</h2><h3>Objectives</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> 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). <h3>Discussion</h3> 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.