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      Fungal infections in adult patients on extracorporeal life support

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          Abstract

          Background

          Patients on extracorporeal membrane oxygenation (ECMO) are often among the most severely ill in the intensive care unit. They are often receiving broad-spectrum antibiotics; they have multiple entry points for pathogens; and their immune system is impaired by blood circuit interaction. These factors are thought to predispose them to fungal infections. We thus aimed to evaluate the prevalence, risk factors, and prognosis of fungal infections in adults on ECMO.

          Methods

          We conducted a retrospective cohort study using the Extracorporeal Life Support Organization registry, which compiles data on ECMO use from hundreds of international centers. We included all adult patients from 2006 to 2016 on any mode of ECMO with either a diagnosis of fungal infection or a positive fungal culture.

          Results

          Our study comprised 2129 adult patients (10.8%) with fungal colonization or infection. Aspergillus involvement (colonization or infection) was present in 272 patients (1.4%), of whom 35.7% survived to hospital discharge. There were 245 patients (1.2%) with Candida invasive bloodstream infection, with 35.9% survival. Risk factors for Aspergillus involvement included solid organ transplant (OR 1.83; p = 0.008), respiratory support (OR 2.75; p < 0.001), and influenza infection (OR 2.48; p < 0.001) . Risk factors for candidemia included sepsis (OR 1.60; p = 0.005) and renal replacement therapy (OR 1.55; p = 0.007). In multivariable analysis, Aspergillus involvement (OR 0.40; p < 0.001) and candidemia (OR 0.47; p < 0.001) were both independently associated with decreased survival.

          Conclusions

          The prevalence of Aspergillus involvement and Candida invasive bloodstream infection were not higher in patients on ECMO than what has been reported in the general intensive care population. Both were independently associated with a reduced survival. Aspergillus involvement was strongly associated with ECMO for respiratory support and influenza.

          Electronic supplementary material

          The online version of this article (10.1186/s13054-018-2023-z) contains supplementary material, which is available to authorized users.

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          Most cited references29

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          NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006-2007.

          Alicia I. Hidron, Jonathan Edwards, Jean Patel … (2008)
          To describe the frequency of selected antimicrobial resistance patterns among pathogens causing device-associated and procedure-associated healthcare-associated infections (HAIs) reported by hospitals in the National Healthcare Safety Network (NHSN). Data are included on HAIs (ie, central line-associated bloodstream infections, catheter-associated urinary tract infections, ventilator-associated pneumonia, and surgical site infections) reported to the Patient Safety Component of the NHSN between January 2006 and October 2007. The results of antimicrobial susceptibility testing of up to 3 pathogenic isolates per HAI by a hospital were evaluated to define antimicrobial-resistance in the pathogenic isolates. The pooled mean proportions of pathogenic isolates interpreted as resistant to selected antimicrobial agents were calculated by type of HAI and overall. The incidence rates of specific device-associated infections were calculated for selected antimicrobial-resistant pathogens according to type of patient care area; the variability in the reported rates is described. Overall, 463 hospitals reported 1 or more HAIs: 412 (89%) were general acute care hospitals, and 309 (67%) had 200-1,000 beds. There were 28,502 HAIs reported among 25,384 patients. The 10 most common pathogens (accounting for 84% of any HAIs) were coagulase-negative staphylococci (15%), Staphylococcus aureus (15%), Enterococcus species (12%), Candida species (11%), Escherichia coli (10%), Pseudomonas aeruginosa (8%), Klebsiella pneumoniae (6%), Enterobacter species (5%), Acinetobacter baumannii (3%), and Klebsiella oxytoca (2%). The pooled mean proportion of pathogenic isolates resistant to antimicrobial agents varied significantly across types of HAI for some pathogen-antimicrobial combinations. As many as 16% of all HAIs were associated with the following multidrug-resistant pathogens: methicillin-resistant S. aureus (8% of HAIs), vancomycin-resistant Enterococcus faecium (4%), carbapenem-resistant P. aeruginosa (2%), extended-spectrum cephalosporin-resistant K. pneumoniae (1%), extended-spectrum cephalosporin-resistant E. coli (0.5%), and carbapenem-resistant A. baumannii, K. pneumoniae, K. oxytoca, and E. coli (0.5%). Nationwide, the majority of units reported no HAIs due to these antimicrobial-resistant pathogens.
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            Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in intensive care unit study.

            P Echeverria, Jean-Louis Vincent, Daniel H Kett … (2011)
            To provide a global, up-to-date picture of the prevalence, treatment, and outcomes of Candida bloodstream infections in intensive care unit patients and compare Candida with bacterial bloodstream infection. A retrospective analysis of the Extended Prevalence of Infection in the ICU Study (EPIC II). Demographic, physiological, infection-related and therapeutic data were collected. Patients were grouped as having Candida, Gram-positive, Gram-negative, and combined Candida/bacterial bloodstream infection. Outcome data were assessed at intensive care unit and hospital discharge. EPIC II included 1265 intensive care units in 76 countries. Patients in participating intensive care units on study day. None. Of the 14,414 patients in EPIC II, 99 patients had Candida bloodstream infections for a prevalence of 6.9 per 1000 patients. Sixty-one patients had candidemia alone and 38 patients had combined bloodstream infections. Candida albicans (n = 70) was the predominant species. Primary therapy included monotherapy with fluconazole (n = 39), caspofungin (n = 16), and a polyene-based product (n = 12). Combination therapy was infrequently used (n = 10). Compared with patients with Gram-positive (n = 420) and Gram-negative (n = 264) bloodstream infections, patients with candidemia were more likely to have solid tumors (p < .05) and appeared to have been in an intensive care unit longer (14 days [range, 5-25 days], 8 days [range, 3-20 days], and 10 days [range, 2-23 days], respectively), but this difference was not statistically significant. Severity of illness and organ dysfunction scores were similar between groups. Patients with Candida bloodstream infections, compared with patients with Gram-positive and Gram-negative bloodstream infections, had the greatest crude intensive care unit mortality rates (42.6%, 25.3%, and 29.1%, respectively) and longer intensive care unit lengths of stay (median [interquartile range]) (33 days [18-44], 20 days [9-43], and 21 days [8-46], respectively); however, these differences were not statistically significant. Candidemia remains a significant problem in intensive care units patients. In the EPIC II population, Candida albicans was the most common organism and fluconazole remained the predominant antifungal agent used. Candida bloodstream infections are associated with high intensive care unit and hospital mortality rates and resource use.
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              Pulmonary pathologic findings of fatal 2009 pandemic influenza A/H1N1 viral infections.

              Mike Bray, Zong-Mei Sheng, Stephanie Gill … (2010)
              In March 2009, a novel swine-origin influenza A/H1N1 virus was identified. After global spread, the World Health Organization in June declared the first influenza pandemic in 41 years. To describe the clinicopathologic characteristics of 34 people who died following confirmed A/H1N1 infection with emphasis on the pulmonary pathology findings. We reviewed medical records, autopsy reports, microbiologic studies, and microscopic slides of 34 people who died between May 15 and July 9, 2009, and were investigated either by the New York City Office of Chief Medical Examiner (32 deaths) or through the consultation service of a coauthor (2 deaths). Most of the 34 decedents (62%) were between 25 and 49 years old (median, 41.5 years). Tracheitis, bronchiolitis, and diffuse alveolar damage were noted in most cases. Influenza viral antigen was observed most commonly in the epithelium of the tracheobronchial tree but also in alveolar epithelial cells and macrophages. Most cases were reverse transcription-polymerase chain reaction positive for influenza. Histologic and microbiologic autopsy evidence of bacterial pneumonia was detected in 55% of cases. Underlying medical conditions including cardiorespiratory diseases and immunosuppression were present in 91% of cases. Obesity (body mass index, >30) was noted in 72% of adult and adolescent cases. The pulmonary pathologic findings in fatal disease caused by the novel pandemic influenza virus are similar to findings identified in past pandemics. Superimposed bacterial infections of the respiratory tract were common. Preexisting obesity, cardiorespiratory diseases, and other comorbidities also were prominent findings among the decedents.
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                Author and article information

                Contributors
                Yiorgos Alexandros Cavayas:
                ORCID: http://orcid.org/0000-0001-7664-2104
                +1-514-802-4889 , yiorgos.alexandros.cavayas@umontreal.ca
                Hakeem Yusuff: +44 300 303 1573 , hakeem.yusuff@uhl-tr.nhs.uk
                Richard Porter: +44 300 303 1573 , richard.porter@uhl-tr.nhs.uk
                Journal
                Journal ID (nlm-ta): Crit Care
                Title: Critical Care
                Publisher: BioMed Central (London )
                ISSN (Print): 1364-8535
                ISSN (Electronic): 1466-609X
                Publication date (Electronic): 17 April 2018
                Publication date PMC-release: 17 April 2018
                Publication date Collection: 2018
                Volume: 22
                Electronic Location Identifier: 98
                Affiliations
                [1 ]ISNI 0000 0001 2160 7387, GRID grid.414056.2, Département de Soins Critiques, , Hôpital Sacré-Coeur de Montréal, ; 5400 Boul Gouin Ouest, Montreal, QC H4J 1C5 Canada
                [2 ]ISNI 0000 0004 0400 6581, GRID grid.412925.9, University Hospitals of Leicester, ECMO program, , Glenfield Hospital, ; Groby Rd, Leicester, LE3 9QP UK
                Author information
                http://orcid.org/0000-0001-7664-2104
                Article
                Publisher ID: 2023
                DOI: 10.1186/s13054-018-2023-z
                PMC ID: 5905180
                PubMed ID: 29665838
                SO-VID: d2e5c17e-37c3-46ef-9707-32fa7a87add1
                Copyright © © The Author(s). 2018
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 17 January 2018
                Date accepted : 28 March 2018
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2018

                ScienceOpen disciplines: Emergency medicine & Trauma
                Keywords: extracorporeal membrane oxygenation [d015199],invasive fungal infections [d000072742],aspergillus [d001230],aspergillosis [d001228],candida [d002175],candidemia [d058387]
                Data availability:
                ScienceOpen disciplines: Emergency medicine & Trauma
                Keywords: extracorporeal membrane oxygenation [d015199], invasive fungal infections [d000072742], aspergillus [d001230], aspergillosis [d001228], candida [d002175], candidemia [d058387]

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