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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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