Risk factors for infections caused by carbapenem-resistant Enterobacterales: an international matched case-control-control study (EURECA)
Salvador Pérez-Galera, José María Bravo-Ferrer, María Paniagua‐García, Tomislav Kostyanev, Marlieke E.A. de Kraker, Jan Feifel, Jesús Sojo-Dorado, Joost Schotsman, Rafael Cantón, George L. Daikos, Biljana Carević, Gorana Dragovac, Lionel Tan, Lul Raka, Adriana Hristea, Pierluigi Viale, Murat Akova, J.M. Reguera, Lucía Valiente de Santis, Julián Torre-Cisneros, Ángela Cano, Emmanuel Roilides, Lili Radulovic, Cenk Kıraklı, Evelyn Shaw, Matthew E. Falagas, Vicente Pintado, Herman Goossens, Marc J. M. Bonten, Belén Gutiérrez‐Gutiérrez, Jesús Rodríguez‐Baño, Almudena de la Serna, Sophie Monteau, Virginia Palomo, Elena Soriano, David Gutierrez, Elisa Moreno, Zaira Palacios, Isabel Morales, Natália Maldonado, Antonio Plata, Juan Diego Ruiz Mesa, Beatriz Sobrino Diaz, Ignacio Márquez Gómez, Inés Pérez Camacho, Azahara Frutos-Adame, Julia Guzmán-Puche, Irene Gracia-Ahufinger, Elena Pérez‐Nadales, Julián Torre-Giménez, Athina Pyrpasopoulou, Εlias Iosifidis, Elsa Chorafa, Ivana Radovanović, Sladjana Petrović, Slavica Cvetkovi, Srdjan-Sanja Melentijevic, Can Biçmen, Güneş Şenol, Fé Tubau, Jordi Cámara, Victor Daniel Gumucio, Dimitris Bassoulis, John Deliolanis, Vassiliki Pitiriga, Nikolaos A. Triarides, Efstathia Argiti, Nikolaos J. Legakis, Kyriakidou Margarita, Desirée Gijón-Cordero, Patricia Ruíz-Garbajosa, Alessandro Bartoloni, Gian María Rossolini, Simin Aysel Florescu, Maria Nica, Șerban Benea, Daniela Tălăpan, Deana Medić, Sanja Maričić Prijić, Mireia Cantero Caballero, Lina M Parra Ramírez, Volkan Korten, Hüseyin Bilgin, George Ν. 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, A Vâţă
Abstract
Background: Data on risk factors for carbapenem-resistant Enterobacterales (CRE) with wider applicability are needed to inform preventive measures and efficient design of randomised trials. Methods: An international matched case-control-control study was performed in 50 hospitals with high CRE incidence from March 2016 to November 2018 to investigate different aspects of infections caused by CRE (NCT02709408). Cases were patients with complicated urinary tract infection (cUTI), complicated intraabdominal (cIAI), pneumonia or bacteraemia from other sources (BSI-OS) due to CRE; control groups were patients with infection caused by carbapenem-susceptible Enterobacterales (CSE), and by non-infected patients, respectively. Matching criteria included type of infection for CSE group, ward and duration of hospital admission. Conditional logistic regression was used to identify risk factors. Findings: Overall, 235 CRE case patients, 235 CSE controls and 705 non-infected controls were included. The CRE infections were cUTI (133, 56.7%), pneumonia (44, 18.7%), cIAI and BSI-OS (29, 12.3% each). Carbapenemase genes were found in 228 isolates: OXA-48/like, 112 (47.6%), KPC, 84 (35.7%), and metallo-β-lactamases, 44 (18.7%); 13 produced two. The risk factors for CRE infection in both type of controls were (adjusted OR for CSE controls; 95% CI; p value) previous colonisation/infection by CRE (6.94; 2.74-15.53; <0.001), urinary catheter (1.78; 1.03-3.07; 0.038) and exposure to broad spectrum antibiotics, as categorical (2.20; 1.25-3.88; 0.006) and time-dependent (1.04 per day; 1.00-1.07; 0.014); chronic renal failure (2.81; 1.40-5.64; 0.004) and admission from home (0.44; 0.23-0.85; 0.014) were significant only for CSE controls. Subgroup analyses provided similar results. Interpretation: The main risk factors for CRE infections in hospitals with high incidence included previous colonization, urinary catheter and exposure to broad spectrum antibiotics. Funding: The study was funded by the Innovative Medicines Initiative Joint Undertaking (https://www.imi.europa.eu/) under Grant Agreement No. 115620 (COMBACTE-CARE).