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. 2023 Feb 27:57:101871.
doi: 10.1016/j.eclinm.2023.101871. eCollection 2023 Mar.

Risk factors for infections caused by carbapenem-resistant Enterobacterales: an international matched case-control-control study (EURECA)

Salvador Pérez-Galera  1   2 , Jose M Bravo-Ferrer  1 , María Paniagua  1 , Tomislav Kostyanev  3   4 , Marlieke E A de Kraker  5 , Jan Feifel  6 , Jesús Sojo-Dorado  1 , Joost Schotsman  7 , Rafael Cantón  8   9 , George L Daikos  10 , Biljana Carevic  11 , Gorana Dragovac  12 , Lionel K Tan  13 , Lul Raka  14 , Adriana Hristea  15 , Pierluigi Viale  16 , Murat Akova  17 , Jose María Reguera  18 , Lucía Valiente de Santis  18 , Julián Torre-Cisneros  9   19 , Ángela Cano  19 , Emmanuel Roilides  20 , Lili Radulovic  21 , Cenk Kirakli  22 , Evelyn Shaw  9   23 , Matthew E Falagas  24   25 , Vicente Pintado  8   9 , Herman Goossens  3 , Marc J Bonten  6 , Belén Gutiérrez-Gutiérrez  1   9 , Jesús Rodriguez-Baño  1   9 ; COMBACTE-CARE-EURECA Team
Collaborators, Affiliations

Risk factors for infections caused by carbapenem-resistant Enterobacterales: an international matched case-control-control study (EURECA)

Salvador Pérez-Galera et al. EClinicalMedicine. .

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).

Keywords: Antimicrobial resistance; Carbapenem-resistant Enterobacterales; KPC; Metallo-beta-lactamases; OXA; Risk factors.

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Conflict of interest statement

George L. Daikos reports personal fees from Pfizer, personal fees from MSD, outside the submitted work. Lionel K. Tan is an employee of and holds stocks and shares in GlaxoSmithKline. Pierluigi Viale reports grants from Shionogi and Gilead; personal fees from Shionogi, MSD, Allianz, Nordic, InfectoPharm, MundiPharm and Angelini, outside the submitted work. Jose María Reguera reports non-financial support from Pfizer. Lucía Valiente de Santis reports non-financial support from Pfizer. Julián Torre-Cisneros reports personal fees from MSD, Pfizer, Menarini, and Shionogi; and non-financial support from Pfizer, Shionogi and Gilead, outside the submitted work. Ángela Cano reports personal fees from Shionogi. Emmanuel Roilides reports personal fees from Amplyx, Astellas, Gilead, MSD, Pfizer, Scynexis, GSK and Shionogi, outside the submitted work. Marc J. Bonten reports grants paid to his institution from Janssen Vaccines, Novartis, CureVac and Merck; participation in Advisory Boards with payment to his institution from Spherecydes, Pfizer, Merck and Astra-Zeneca, and participation in Data Safety Monitoring Boards with payment to his institution from Sanofi. All other authors have no conflicts to declare.

Figures

Fig. 1
Fig. 1
Chord diagram for the distribution of exposure to key variables in the CRE (green), CSE (blue) and non-infected (pink) groups. The width of the ribbons correlates with the proportion of patients exposed to each variable in the respective group.
See this image and copyright information in PMC

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