Risk factors for bloodstream infections due to carbapenem-resistant Enterobacterales: a nested case-control-control study
Authors: Zhou Hongyu , Buetti Niccolò , Pérez-Galera Salvador , Bravo-Ferrer Jose , Gutiérrez-Gutiérrez Belén , Paniagua-García María , Feifel Jan , Sauser Julien , Kostyanev Tomi , Canton Rafael , Tan Lionel K , Basoulis Dimitris , Pintado Vicente , Roilides Emmanuel , Dragovac Gorana , Torre-Cisneros Julian , Mediç Deana , Akova Murat , Goossens Herman , Bonten Marc , Harbarth Stephan , Rodriguez-Baño Jesus , De Kraker Marlieke E A ,   COMBACTE- EURECA project team, Sojo-Dorado Jesus , de la Serna Almudena , Monteau Sophie , Palomo Virginia , Soriano Elena , Gutiérrez David , Moreno Elisa , Palacios Zaira , Morales Isabel , Maldonado Natalia , Reguera Jose Maria , de Santis Lucia Valiente , Ciezar Antonio Plata , Mesa Juan Diego Ruiz , Diaz Beatriz Sobrino , Gomez Ignacio Marquez , Camacho Ines Perez , Palop Begoña , Torre-Cisneros Julian , Cano Angela , Frutos-Adame Azahara , Guzman-Puche Julia , Gracia-Ahufinger Irene , Perez-Nadales Elena , Torre-Gimenez Julian , Pyrpasopoulou Athina , Iosifidis Elias , Chorafa Elsa , Carevic Biljana , Jovanovic Snezana , Radovanovic Ivana , Petrovic Sladjana , Cvetkovi Slavica , Radulovic Lili , Melentijevic Srdjan-Sanja , Miljkovic Natasa , Perucica Ana , Kirakli Cenk , Bicmen Can , Senol Gunes , Shaw Evelyn , Tubau Fe , Camara Jordi , Gumucio Victor Daniel , Daikos George L , Deliolanis John , Falagas Matthew E , Ch. Pitiriga Vassiliki , Triarides Nikolaos , Argiti Efstathia , Legakis Nikolaos J , Margarita Kyriakidou , Gijón-Cordero Desirée , Ruiz-Garbajosa Patricia , Suarez Amaya , Bartoloni Alessandro , Rossolini Gian Maria , Florescu Simin-Aysel , Nica Maria , Benea Serban , Talapan Daniela , Hristea Adriana , Maričić Sanja Prijić , Jovetic Anita , Milenkovic Marija Zivanovic , Asensio Angel , Caballero Mireia Cantero , Ramírez Lina M Parra , Ruiz-Antoran Belen , Layunta-Acero Rocio , Ruiz-Antoran Belen , Korten Volkan , Bilgin Hüseyin , Hasdemir Ufuk , Dalekos George N , Stefos Aggelos , Petinaki Efthymia , Spyridis Nikolaos , Michos Athanasios , De Rosa Francesco Giuseppe , Cavallo Rossana , Petrosillo Nicola , Dicaro Antonio , Viale Pierluigi , Landini Maria Paola , degli Atti Marta Luisa Ciofi , Masanovic Mileva , Matkovic Dusan , Satic Dragan , Lopicic Milena , Tsiodras Sotirios , Zerva Loukia , Blasi Francesco , Di Pasquale Marta , Arghittu Milena , Viscoli Claudio , Giacobbe Daniele Roberto , Marchese Anna , Vata Andrei , Dorneanu Olivia , Kapisyzi Perlat , Tafaj Silva , Vince Adriana , Andrasevic Arjana Tambic , Butic Iva , Tsigou Evdoxia , Gavala Alexandra , Biniari Theodora , Maltezos Efstratios , Komnos Apostolos , Karagiannis Spyros , Tsalakou Maria , Voulgaridi Ioanna , Gogos Charalampos , Spiliopoulou Iris , Franzetti Fabio , Rimoldi Sara , Antonelli Massimo , De Pascale Gennaro , Di Gravio Valentina , Spanu Teresa , Lupse Mihaela , Flonta Mirela , Corneci Dan , Buzea Mariana , Tomescu Dana , Marcu Alexandra , Ghita Camelia , Georgescu Anca , Azamfirei Leonard , Székely Edit , Mitrović Goran , Bukarica Ljiljana , Vitorovic Teodora , Krstić Nataša Lukić , Mitrovic Goran , Kocic Branislava , Dinic Marina , Raka Lul , Kurti Arsim , Díaz-Pollán Beatriz , Loeches Belen , López Jose Ramón Arribas , Sabater Julia Origüen , Chaves Fernando , Muñoz Patricia , Azap Alpay , Karahan Ceren , Sancak Banu , Sahin Arife , Akalin Halis , Ozakin Cüneyt 
Published: July 2024

Abstract

Background
Carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) are a major threat to patients. To date, data on risk factors have been limited, with low internal and external validity. In this multicentre study, risk factors for CRE BSI were determined by comparison with two control groups: patients with carbapenem-susceptible Enterobacterales (CSE) BSI, and patients without Enterobacterales infection (uninfected patients).

Methods
A multicentre, case-control-control study was nested in a European prospective cohort study on CRE (EURECA). CRE BSI:CSE BSI matching was 1:1, CRE BSI:Uninfected patients matching was 1:3, based on hospital, ward and length of stay. Conditional logistic regression was applied.

Results
From March 2016 to November 2018, 73 CRE BSIs, 73 CSE BSIs and 219 uninfected patients were included from 18 European hospitals. For CRE versus CSE BSI, previous CRE colonization/infection [incidence rate ratio (IRR) 7.32; 95% CI 1.65–32.38) increased the risk. For CRE versus uninfected controls, independent risk factors included: older age (IRR 1.03; 95% CI 1.01–1.06), patient referral (long-term care facility: IRR 7.19; 95% CI 1.51–34.24; acute care hospital: IRR 5.26; 95% CI 1.61–17.11), previous colonization/infection with other MDR organisms (MDROs) (IRR 9.71; 95% CI 2.33–40.56), haemodialysis (IRR 8.59; 95% CI 1.82–40.53), invasive procedures (IRR 5.66; 95% CI 2.11–15.16), and β-lactam/β-lactamase inhibitor combinations (IRR 3.92; 95% CI 1.68–9.13) or third/fourth generation cephalosporin (IRR 2.75; 95% CI 1.06–7.11) exposure within 3 months before enrolment.

Conclusions
Evidence of previous CRE colonization/infection was a major risk factor for carbapenem resistance among Enterobacterales BSI. Compared with uninfected patients, evidence of previous MDRO colonization/infection and healthcare exposure were important risk factors for CRE BSI. Targeted screening, infection prevention and antimicrobial stewardship should focus on these high-risk patients.