EClinicalMedicine (Mar 2023)
Risk factors for infections caused by carbapenem-resistant Enterobacterales: an international matched case-control-control study (EURECA)Research in context
- Salvador Pérez-Galera,
- Jose M. Bravo-Ferrer,
- María Paniagua,
- Tomislav Kostyanev,
- Marlieke E.A. de Kraker,
- Jan Feifel,
- Jesús Sojo-Dorado,
- Joost Schotsman,
- Rafael Cantón,
- George L. Daikos,
- Biljana Carevic,
- Gorana Dragovac,
- Lionel K. Tan,
- Lul Raka,
- Adriana Hristea,
- Pierluigi Viale,
- Murat Akova,
- Jose María Reguera,
- Lucía Valiente de Santis,
- Julián Torre-Cisneros,
- Ángela Cano,
- Emmanuel Roilides,
- Lili Radulovic,
- Cenk Kirakli,
- Evelyn Shaw,
- Matthew E. Falagas,
- Vicente Pintado,
- Herman Goossens,
- Marc J. Bonten,
- Belén Gutiérrez-Gutiérrez,
- Jesús Rodriguez-Baño,
- Almudena de la Serna,
- Sophie Monteau,
- Virginia Palomo,
- Elena Soriano,
- David Gutierrez,
- Elisa Moreno,
- Zaira Palacios,
- Isabel Morales,
- Natalia Maldonado,
- Antonio Plata Ciezar,
- Juan Diego Ruiz Mesa,
- Beatriz Sobrino Diaz,
- Ignacio Marquez Gomez,
- Ines Perez Camacho,
- 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,
- Alessandro Bartoloni,
- Gian Maria Rossolini,
- Simin-Aysel Florescu,
- Maria Nica,
- Serban Benea,
- Daniela Talapan,
- Deana Medić,
- Sanja Maričić Prijić,
- Mireia Cantero Caballero,
- Lina M. Parra Ramírez,
- Volkan Korten,
- 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,
- Massimo Antonelli,
- Mihaela Lupse,
- Dan Corneci,
- Dana Tomescu,
- Anca Georgescu,
- Ljiljana Bukarica,
- Goran Mitrović,
- Nataša Lukić Krstić,
- Arsim Kurti,
- Beatriz Díaz-Pollán,
- Julia Origüen Sabater,
- Patricia Muñoz,
- Alpay Azap,
- Banu Sancak,
- Arife Sahin,
- Halis Akalin
Affiliations
- Salvador Pérez-Galera
- Unidad de Enfermedades y Microbiología, Hospital Universitario Virgen Macarena and Departamento de Medicina, Universidad de Sevilla/Instituto de Biomedicina de Sevilla/CSIC, Seville, Spain; Servicio de Medicina Interna, Hospital Universitario Virgen Macarena, Seville, Spain
- Jose M. Bravo-Ferrer
- Unidad de Enfermedades y Microbiología, Hospital Universitario Virgen Macarena and Departamento de Medicina, Universidad de Sevilla/Instituto de Biomedicina de Sevilla/CSIC, Seville, Spain
- María Paniagua
- Unidad de Enfermedades y Microbiología, Hospital Universitario Virgen Macarena and Departamento de Medicina, Universidad de Sevilla/Instituto de Biomedicina de Sevilla/CSIC, Seville, Spain
- Tomislav Kostyanev
- Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium; Laboratoire National de Santé, Luxembourg, Luxembourg
- Marlieke E.A. de Kraker
- Infection Control Program, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
- Jan Feifel
- Institute of Statistics, Ulm University, Ulm, Germany
- Jesús Sojo-Dorado
- Unidad de Enfermedades y Microbiología, Hospital Universitario Virgen Macarena and Departamento de Medicina, Universidad de Sevilla/Instituto de Biomedicina de Sevilla/CSIC, Seville, Spain
- Joost Schotsman
- Department of Medical Microbiology and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
- Rafael Cantón
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
- George L. Daikos
- Laiko General Hospital, National and Kapodistrian University of Athens, Athens, Greece
- Biljana Carevic
- Department of Hospital Epidemiology, Clinical Center of Serbia, Belgrade, Serbia
- Gorana Dragovac
- Faculty of Medicine and Institute of Public Health of Vojvodina, University of Novi Sad, Novi Sad, Serbia
- Lionel K. Tan
- GSK, Brentford, UK
- Lul Raka
- University of Prishtina “Hasan Prishtina” and National Institute of Public Health of Kosovo, Prishtina, Kosovo
- Adriana Hristea
- University of Medicine and Pharmacy ‘Carol Davila’, Bucharest, Romania
- Pierluigi Viale
- Malattie Infettive, Policlinico Sant'Orsola, Bologna, Italy
- Murat Akova
- Department of Infectious Diseases and Clinical Microbiology, Hacettepe University Faculty of Medicine, Sihhiye, Ankara, Turkey
- Jose María Reguera
- Servicio de Enfermedades Infecciosas, Hospital Regional Universitario de Málaga, Ibima, Málaga, Spain
- Lucía Valiente de Santis
- Servicio de Enfermedades Infecciosas, Hospital Regional Universitario de Málaga, Ibima, Málaga, Spain
- Julián Torre-Cisneros
- CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain; Servicio de Enfermedades Infecciosas Hospital Universitario Reina Sofía/Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/Universidad de Córdoba (Departamento de Ciencias Médicas y Quirúrgicas), Córdoba, Spain
- Ángela Cano
- Servicio de Enfermedades Infecciosas Hospital Universitario Reina Sofía/Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/Universidad de Córdoba (Departamento de Ciencias Médicas y Quirúrgicas), Córdoba, Spain
- Emmanuel Roilides
- Hippokration General Hospital of Thessaloniki, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
- Lili Radulovic
- Zvezdara University Medical Center, Belgrade, Serbia
- Cenk Kirakli
- Dr. Suat Seren Chest Diseases and Surgery Training Hospital, Izmir, Turkey
- Evelyn Shaw
- CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain; Department of Infectious Diseases, Hospital Universitari de Bellvitge, Institut d’Investigacions Biomèdiques de Bellvitge/IDIBELL, Barcelona, Spain
- Matthew E. Falagas
- Henry Dunant Hospital Center, Athens, Greece; Metropolitan General Hospital, Athens, Greece
- Vicente Pintado
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
- Herman Goossens
- Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
- Marc J. Bonten
- Institute of Statistics, Ulm University, Ulm, Germany
- Belén Gutiérrez-Gutiérrez
- Unidad de Enfermedades y Microbiología, Hospital Universitario Virgen Macarena and Departamento de Medicina, Universidad de Sevilla/Instituto de Biomedicina de Sevilla/CSIC, Seville, Spain; CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
- Jesús Rodriguez-Baño
- Unidad de Enfermedades y Microbiología, Hospital Universitario Virgen Macarena and Departamento de Medicina, Universidad de Sevilla/Instituto de Biomedicina de Sevilla/CSIC, Seville, Spain; CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain; Corresponding author. Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena, Avda Dr Fedriani 3, Seville 41009, Spain.
- Almudena de la Serna
- Sophie Monteau
- Virginia Palomo
- Elena Soriano
- David Gutierrez
- Elisa Moreno
- Zaira Palacios
- Isabel Morales
- Natalia Maldonado
- Antonio Plata Ciezar
- Juan Diego Ruiz Mesa
- Beatriz Sobrino Diaz
- Ignacio Marquez Gomez
- Ines Perez Camacho
- 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
- Alessandro Bartoloni
- Gian Maria Rossolini
- Simin-Aysel Florescu
- Maria Nica
- Serban Benea
- Daniela Talapan
- Deana Medić
- Sanja Maričić Prijić
- Mireia Cantero Caballero
- Lina M. Parra Ramírez
- Volkan Korten
- 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
- Massimo Antonelli
- Mihaela Lupse
- Dan Corneci
- Dana Tomescu
- Anca Georgescu
- Ljiljana Bukarica
- Goran Mitrović
- Nataša Lukić Krstić
- Arsim Kurti
- Beatriz Díaz-Pollán
- Julia Origüen Sabater
- Patricia Muñoz
- Alpay Azap
- Banu Sancak
- Arife Sahin
- Halis Akalin
- Journal volume & issue
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Vol. 57
p. 101871
Abstract
Summary: 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).