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      Ventilator-associated pneumonia in patients with SARS-CoV-2-associated acute respiratory distress syndrome requiring ECMO: a retrospective cohort study

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          Abstract

          Background

          The data on incidence, clinical presentation, and outcomes of ventilator-associated pneumonia (VAP) in patients with severe coronavirus disease 2019 (COVID-19) pneumonia requiring mechanical ventilation (MV) are limited. We performed this retrospective cohort study to assess frequency, clinical characteristics, responsible pathogens, and outcomes of VAP in patients COVID-19 pneumonia requiring MV between March 12th and April 24th, 2020 (all had RT-PCR-confirmed SARS-CoV-2 infection). Patients with COVID-19-associated acute respiratory distress syndrome (ARDS) requiring ECMO were compared with an historical cohort of 45 patients with severe influenza-associated ARDS requiring ECMO admitted to the same ICU during the preceding three winter seasons.

          Results

          Among 50 consecutive patients with Covid-19-associated ARDS requiring ECMO included [median (IQR) age 48 (42–56) years; 72% male], 43 (86%) developed VAP [median (IQR) MV duration before the first episode, 10 (8–16) days]. VAP-causative pathogens were predominantly Enterobacteriaceae (70%), particularly inducible AmpC-cephalosporinase producers (40%), followed by Pseudomonas aeruginosa (37%). VAP recurred in 34 (79%) patients and 17 (34%) died. Most recurrences were relapses (i.e., infection with the same pathogen), with a high percentage occurring on adequate antimicrobial treatment. Estimated cumulative incidence of VAP, taking into account death and extubation as competing events, was significantly higher in Covid-19 patients than in influenza patients ( p = 0.002). Despite a high P. aeruginosa-VAP rate in patients with influenza-associated ARDS (54%), the pulmonary infection recurrence rate was significantly lower than in Covid-19 patients. Overall mortality was similar for the two groups.

          Conclusions

          Patients with severe Covid-19-associated ARDS requiring ECMO had a very high late-onset VAP rate. Inducible AmpC-cephalosporinase-producing Enterobacteriaceae and Pseudomonas aeruginosa frequently caused VAP, with multiple recurrences and difficulties eradicating the pathogen from the lung.

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          Most cited references24

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          Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China

          Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated.
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            Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19

            Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (Covid-19) pandemic. Despite widespread interest in the pathophysiology of the disease, relatively little is known about the associated morphologic and molecular changes in the peripheral lung of patients who die from Covid-19.
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              Acute respiratory distress syndrome: the Berlin Definition.

              The acute respiratory distress syndrome (ARDS) was defined in 1994 by the American-European Consensus Conference (AECC); since then, issues regarding the reliability and validity of this definition have emerged. Using a consensus process, a panel of experts convened in 2011 (an initiative of the European Society of Intensive Care Medicine endorsed by the American Thoracic Society and the Society of Critical Care Medicine) developed the Berlin Definition, focusing on feasibility, reliability, validity, and objective evaluation of its performance. A draft definition proposed 3 mutually exclusive categories of ARDS based on degree of hypoxemia: mild (200 mm Hg < PaO2/FIO2 ≤ 300 mm Hg), moderate (100 mm Hg < PaO2/FIO2 ≤ 200 mm Hg), and severe (PaO2/FIO2 ≤ 100 mm Hg) and 4 ancillary variables for severe ARDS: radiographic severity, respiratory system compliance (≤40 mL/cm H2O), positive end-expiratory pressure (≥10 cm H2O), and corrected expired volume per minute (≥10 L/min). The draft Berlin Definition was empirically evaluated using patient-level meta-analysis of 4188 patients with ARDS from 4 multicenter clinical data sets and 269 patients with ARDS from 3 single-center data sets containing physiologic information. The 4 ancillary variables did not contribute to the predictive validity of severe ARDS for mortality and were removed from the definition. Using the Berlin Definition, stages of mild, moderate, and severe ARDS were associated with increased mortality (27%; 95% CI, 24%-30%; 32%; 95% CI, 29%-34%; and 45%; 95% CI, 42%-48%, respectively; P < .001) and increased median duration of mechanical ventilation in survivors (5 days; interquartile [IQR], 2-11; 7 days; IQR, 4-14; and 9 days; IQR, 5-17, respectively; P < .001). Compared with the AECC definition, the final Berlin Definition had better predictive validity for mortality, with an area under the receiver operating curve of 0.577 (95% CI, 0.561-0.593) vs 0.536 (95% CI, 0.520-0.553; P < .001). This updated and revised Berlin Definition for ARDS addresses a number of the limitations of the AECC definition. The approach of combining consensus discussions with empirical evaluation may serve as a model to create more accurate, evidence-based, critical illness syndrome definitions and to better inform clinical care, research, and health services planning.
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                Author and article information

                Contributors
                charles-edouard.luyt@aphp.fr
                Journal
                Ann Intensive Care
                Ann Intensive Care
                Annals of Intensive Care
                Springer International Publishing (Cham )
                2110-5820
                23 November 2020
                23 November 2020
                2020
                : 10
                : 158
                Affiliations
                [1 ]Service de Médecine Intensive Réanimation, Institut de Cardiologie, ICAN, Assistance Publique-Hôpitaux de Paris (APHP), Sorbonne-Université, Groupe Hospitalier Pitié-Salpêtrière, 47–83, Boulevard de L’Hôpital, 75651 Paris Cedex 13, France
                [2 ]GRID grid.462844.8, ISNI 0000 0001 2308 1657, INSERM, UMRS_1166-ICAN Institute of Cardiometabolism and Nutrition, , Sorbonne Université, ; Paris, France
                [3 ]Service de Bactériologie-Hygiène, APHP, Sorbonne-Université, Hôpital Pitié-Salpêtrière, Paris, France
                [4 ]Centre National de Référence Herpesvirus (Laboratoire Associé), Service de Virologie, Groupe Hospitalo-Universitaire (GHU) AP-HP, Sorbonne Université, Hôpital Pitié-Salpêtrière, Paris, France
                [5 ]GRID grid.462844.8, ISNI 0000 0001 2308 1657, INSERM U1136, Institut Pierre Louis D’Epidémiologie Et de Santé Publique (iPLESP), , Sorbonne Université, ; Paris, France
                [6 ]Département D’Anesthésie-Réanimation, Assistance Publique-Hôpitaux de Paris (APHP), Sorbonne-Université, Hôpital Pitié-Salpêtrière, Paris, France
                Author information
                http://orcid.org/0000-0001-7424-2705
                Article
                775
                10.1186/s13613-020-00775-4
                7682692
                33230710
                0f4bb5e5-b650-4e6d-a967-7e7faa097f92
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 3 August 2020
                : 13 November 2020
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                Emergency medicine & Trauma
                ventilator-associated pneumonia,coronavirus,covid-19,enterobacteriaceae,ecmo,ards

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