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Co-infection and ICU-acquired infection in COVID-19 ICU patients: a secondary analysis of the UNITE-COVID data set
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Abstract
Background
The COVID-19 pandemic presented major challenges for critical care facilities worldwide. Infections which develop alongside or subsequent to viral pneumonitis are a challenge under sporadic and pandemic conditions; however, data have suggested that patterns of these differ between COVID-19 and other viral pneumonitides. This secondary analysis aimed to explore patterns of co-infection and intensive care unit-acquired infections (ICU-AI) and the relationship to use of corticosteroids in a large, international cohort of critically ill COVID-19 patients.
Methods
This is a multicenter, international, observational study, including adult patients with PCR-confirmed COVID-19 diagnosis admitted to ICUs at the peak of wave one of COVID-19 (February 15th to May 15th, 2020). Data collected included investigator-assessed co-infection at ICU admission, infection acquired in ICU, infection with multi-drug resistant organisms (MDRO) and antibiotic use. Frequencies were compared by Pearson’s Chi-squared and continuous variables by Mann–Whitney U test. Propensity score matching for variables associated with ICU-acquired infection was undertaken using R library MatchIT using the “full” matching method.
Results
Data were available from 4994 patients. Bacterial co-infection at admission was detected in 716 patients (14%), whilst 85% of patients received antibiotics at that stage. ICU-AI developed in 2715 (54%). The most common ICU-AI was bacterial pneumonia (44% of infections), whilst 9% of patients developed fungal pneumonia; 25% of infections involved MDRO. Patients developing infections in ICU had greater antimicrobial exposure than those without such infections. Incident density (ICU-AI per 1000 ICU days) was in considerable excess of reports from pre-pandemic surveillance. Corticosteroid use was heterogenous between ICUs. In univariate analysis, 58% of patients receiving corticosteroids and 43% of those not receiving steroids developed ICU-AI. Adjusting for potential confounders in the propensity-matched cohort, 71% of patients receiving corticosteroids developed ICU-AI vs 52% of those not receiving corticosteroids. Duration of corticosteroid therapy was also associated with development of ICU-AI and infection with an MDRO.
Conclusions
In patients with severe COVID-19 in the first wave, co-infection at admission to ICU was relatively rare but antibiotic use was in substantial excess to that indication. ICU-AI were common and were significantly associated with use of corticosteroids.
Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021).
Graphical abstract
Springer Science and Business Media LLC
Andrew Conway Morris
Katharina Kohler
Thomas De Corte
Ari Ercole
Harm-Jan De Grooth
Paul W. G. Elbers
Pedro Povoa
Rui Morais
Despoina Koulenti
Sameer Jog
Nathan Nielsen
Alasdair Jubb
Maurizio Cecconi
Jan De Waele
Marco Bezzi
Alicia Gira
Philipp Eller
Tarikul Hamid
Injamam Ull Haque
Wim De Buyser
Antonella Cudia
Daniel De Backer
Pierre Foulon
Vincent Collin
Jan De Waele
Jolien Van Hecke
Elisabeth De Waele
Claire Van Malderen
Jean-Baptiste Mesland
Michael Piagnerelli
Lionel Haentjens
Nicolas De Schryver
Jan Van Leemput
Philippe Vanhove
Pierre Bulpa
Viktoria Ilieva
David Katz
Anna Geagea
Alexandra Binnie
Fernando Tirapegui
Gustavo Lago
Jerónimo Graf
Rodrigo Perez-Araos
Patricio Vargas
Felipe Martinez
Eduardo Labarca
Daniel Molano Franco
Daniela Parra-Tanoux
Luis Felipe Reyes
David Yepes
Filip Periš
Sanda Stojanović Stipić
Cynthia Vanessa Campozano Burgos
Paulo Roberto Navas Boada
Jose Luis Barberan Brun
Juan Pablo Paredes Ballesteros
Ahmed Hammouda
Omar Elmandouh
Ahmed Azzam
Aliae Mohamed Hussein
Islam Galal
Ahmed K. Awad
Mohammed A. Azab
Maged Abdalla
Hebatallah Assal
Mostafa Alfishawy
Sherief Ghozy
Samar Tharwat
Abdullah Eldaly
Veronika Reinhard
Anne Chrisment
Chrystelle Poyat
Julio Badie
Fernando Berdaguer Ferrari
Björn Weiss
Karl Friedrich Kuhn
Julius J. Grunow
Marco Lorenz
Stefan Schaller
Peter Spieth
Marc Bota
Falk Fichtner
Kristina Fuest
Tobias Lahmer
Johannes Herrmann
Patrick Meybohm
Nikolaos Markou
Georgia Vasileiadou
Evangelia Chrysanthopoulou
Panagiotis Papamichalis
Ioanna Soultati
Sameer Jog
Kushal Kalvit
Sheila Nainan Myatra
Ivan Krupa
Aisa Tharwat
Alistair Nichol
Aine McCarthy
Ata Mahmoodpoor
Tommaso Tonetti
Paolo Isoni
Savino Spadaro
Carlo Alberto Volta
Lucia Mirabella
Alberto Noto
Gaetano Florio
Amedeo Guzzardella
Chiara Paleari
Federica Baccanelli
Marzia Savi
Massimo Antonelli
Barbara Vaccarini
Giorgia Montrucchio
Gabriele Sales
Katia Donadello
Leonardo Gottin
Enrico Polati
Silvia De Rosa
Demet Sulemanji
Abdurraouf Abusalama
Muhammed Elhadi
Montelongo Felipe De Jesus
Daniel Rodriguez Gonzalez
Nancy Canedo
Alejandro Esquivel Chavez
Tarek Dendane
Bart Grady
Ben de Jong
Eveline van der Heiden
Patrick Thoral
Bas van den Bogaard
Peter E. Spronk
Sefanja Achterberg
Melanie Groeneveld
Ralph K. L. So
Calvin de Wijs
Harm Scholten
Albertus Beishuizen
Alexander D. Cornet
Auke C. Reidinga
Hetty Kranen
Roos Mensink
Sylvia den Boer
Marcel de Groot
Oliver Beck
Carina Bethlehem
Bas van Bussel
Tim Frenzel
Celestine de Jong
Rob Wilting
Jozef Kesecioglu
Jannet Mehagnoul-Schipper
Datonye Alasia
Ashok Kumar
Ahad Qayyum
Muhammad Rana
Mustafa Abu Jayyab
Rosario Quispe Sierra
Aaron Mark Hernandez
Lúcia Taborda
Tiago Ramires
Catarina Silva
Carolina Roriz
Pedro Póvoa
Patricia Patricio
Maria Lurdes Santos
Vasco Costa
Pedro Cunha
Celina Gonçalves
Sandra Nunes
João Camões
Diana Adrião
Ana Oliveira
Ali Omrani
Muna Al Maslamani
Abdurrahmaan Suei elbuzidi
Bara Mahmoud Al qudah
Abdel Rauof Akkari
Mohamed Alkhatteb
Anas Baiou
Ahmed Husain
Mohamed Alwraidat
Ibrahim Abdulsalam Saif
Dana Bakdach
Amna Ahmed
Mohamed Aleef
Awadh Bintaher
Cristina Petrisor
Evgeniy Popov
Ksenia Popova
Mariia Dementienko
Boris Teplykh
Alexey Pyregov
Liubov Davydova
Belskii Vladislav
Elena Neporada
Ivan Zverev
Svetlana Meshchaninova
Dmitry Sokolov
Elena Gavrilova
Irena Shlyk
Igor Poliakov
Mapинa Bлacoвa
Ohoud Aljuhani
Amina Alkhalaf
Felwa Bin Humaid
Yaseen Arabi
Ahmed Kuhail
Omar Elrabi
Madihah Alghnam
Amit Kansal
Vui Kian Ho
Jensen Ng
Raquel Rodrígez García
Xiana Taboada Fraga
Mª del Pilar García-Bonillo
Antonio Padilla-Serrano
Marta Martin Cuadrado
Carlos Ferrando
Ignacio Catalan-Monzon
Laura Galarza
Fernando Frutos-Vivar
Jorge Jimenez
Carmen Rodríguez-Solis
Enric Franquesa-Gonzalez
Guillermo Pérez Acosta
Luciano Santana Cabrera
Juan Pablo Aviles Parra
Francisco Muñoyerro Gonzalez
Maria del Carmen Lorente Conesa
Ignacio Yago Martinez Varela
Orville Victoriano Baez Pravia
Maria Cruz Martin Delgado
Carlos Munoz de Cabo
Ana-Maria Ioan
Cesar Perez-Calvo
Arnoldo Santos
Ane Abad-Motos
Javier Ripolles-Melchor
Belén Civantos Martin
Santiago Yus Teruel
Juan Higuera Lucas
Aaron Blandino Ortiz
Raúl de Pablo Sánchez
Jesús Emilio Barrueco-Francioni
Lorena Forcelledo Espina
José M. Bonell-Goytisolo
Iñigo Salaverria
Antonia Socias Mir
Emilio Rodriguez-Ruiz
Virginia Hidalgo Valverde
Patricia Jimeno Cubero
Francisca Arbol Linde
Nieves Cruza Leganes
Juan Maria Romeu
Pablo Concha
José Angel Berezo-Garcia
Virginia Fraile
Cristina Cuenca-Rubio
David Perez-Torres
Ainhoa Serrano
Clara Martínez Valero
Andrea Ortiz Suner
Leire Larrañaga
Noemi Legaristi
Gerardo Ferrigno
Safa Khlafalla
Rosita Bihariesingh-Sanchit
Frank Zoerner
Jonathan Grip
Kristina Kilsand
Jonas Österlind
Magnus von Seth
Johan Berkius
Samuele Ceruti
Andrea Glotta
Seval Izdes
Işıl Özkoçak Turan
Ahmet Cosar
Burcin Halacli
Necla Dereli
Mehmet Yilmaz
Türkay Akbas
Gülseren Elay
Selin Eyüpoğlu
Yelíz Bílír
Kemal Tolga Saraçoğlu
Ebru Kaya
Ayca Sultan Sahin
Pervin Korkmaz Ekren
Tuğçe Mengi
Kezban Ozmen Suner
Yakup Tomak
Ahmet Eroglu
Asad Alsabbah
Katie Hanlon
Kevin Gervin
Sean McMahon
Samantha Hagan
Caroline V. Higenbottam
Randeep Mullhi
Lottie Poulton
Tomasz Torlinski
Allen Gareth
Nick Truman
Gopal Vijayakumar
Chris Hall
Alasdair Jubb
Lenka Cagova
Nicola Jones
Sam Graham
Nicole Robin
Amanda Cowton
Adrian Donnelly
Natalia Singatullina
Melanie Kent
Carole Boulanger
Zoë Campbell
Elizabeth Potter
Natalie Duric
Tamas Szakmany
Orinta Kviatkovske
Nandor Marczin
Caroline Ellis
Rajnish Saha
Chunda Sri-Chandana
John Allan
Lana Mumelj
Harish Venkatesh
Vera Nina Gotz
Anthony Cochrane
Nuttha Lumlertgul
Barbara Ficial
Susan Jain
Giulia Beatrice Crapelli
Aikaterini Vlachou
David Golden
Sweyn Garrioch
Jeremy Henning
Gupta Loveleena
Miriam Davey
Lina Grauslyte
Erika Salciute-Simene
Martin Cook
Danny Barling
Phil Broadhurst
Sarah Purvis
Spivey Michael
Benjamin Shuker
Irina Grecu
Daniel Harding
Natalia Singatullina
James T. Dean
Nathan D. Nielsen
Sama Al-Bayati
Mohammed Al-Sadawi
Mariane Charron
Peter Stubenrauch
Jairo Santanilla
Catherine Wentowski
Dorothea Rosenberger
Polikseni Eksarko
Randeep Jawa
Title: Co-infection and ICU-acquired infection in COVID-19 ICU patients: a secondary analysis of the UNITE-COVID data set
Description:
Abstract
Background
The COVID-19 pandemic presented major challenges for critical care facilities worldwide.
Infections which develop alongside or subsequent to viral pneumonitis are a challenge under sporadic and pandemic conditions; however, data have suggested that patterns of these differ between COVID-19 and other viral pneumonitides.
This secondary analysis aimed to explore patterns of co-infection and intensive care unit-acquired infections (ICU-AI) and the relationship to use of corticosteroids in a large, international cohort of critically ill COVID-19 patients.
Methods
This is a multicenter, international, observational study, including adult patients with PCR-confirmed COVID-19 diagnosis admitted to ICUs at the peak of wave one of COVID-19 (February 15th to May 15th, 2020).
Data collected included investigator-assessed co-infection at ICU admission, infection acquired in ICU, infection with multi-drug resistant organisms (MDRO) and antibiotic use.
Frequencies were compared by Pearson’s Chi-squared and continuous variables by Mann–Whitney U test.
Propensity score matching for variables associated with ICU-acquired infection was undertaken using R library MatchIT using the “full” matching method.
Results
Data were available from 4994 patients.
Bacterial co-infection at admission was detected in 716 patients (14%), whilst 85% of patients received antibiotics at that stage.
ICU-AI developed in 2715 (54%).
The most common ICU-AI was bacterial pneumonia (44% of infections), whilst 9% of patients developed fungal pneumonia; 25% of infections involved MDRO.
Patients developing infections in ICU had greater antimicrobial exposure than those without such infections.
Incident density (ICU-AI per 1000 ICU days) was in considerable excess of reports from pre-pandemic surveillance.
Corticosteroid use was heterogenous between ICUs.
In univariate analysis, 58% of patients receiving corticosteroids and 43% of those not receiving steroids developed ICU-AI.
Adjusting for potential confounders in the propensity-matched cohort, 71% of patients receiving corticosteroids developed ICU-AI vs 52% of those not receiving corticosteroids.
Duration of corticosteroid therapy was also associated with development of ICU-AI and infection with an MDRO.
Conclusions
In patients with severe COVID-19 in the first wave, co-infection at admission to ICU was relatively rare but antibiotic use was in substantial excess to that indication.
ICU-AI were common and were significantly associated with use of corticosteroids.
Trial registration ClinicalTrials.
gov: NCT04836065 (retrospectively registered April 8th 2021).
Graphical abstract.
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