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653. Diagnosis of Burn Sepsis Using the FcMBL ELISA: A Pilot Study in Critically Ill Burn Patients

BACKGROUND: Infection is the leading cause of death among burn survivors, with sepsis associated with more extensive burns. Conventional diagnostic criteria are insensitive in this population. We examined a novel diagnostic ELISA based on Mannose-Binding Lectin (MBL) linked to an immunoglobulin Fc d...

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Autores principales: Akers, Kevin S, Schlotman, Taylor, Mangum, Lee C, Garcia, Gerardo, Wagner, Amanda, Seiler, Benjamin, Cartwright, Mark, Rifai, Sami, Ingber, Donald, Super, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811174/
http://dx.doi.org/10.1093/ofid/ofz360.721
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author Akers, Kevin S
Schlotman, Taylor
Mangum, Lee C
Garcia, Gerardo
Wagner, Amanda
Seiler, Benjamin
Cartwright, Mark
Rifai, Sami
Ingber, Donald
Super, Michael
author_facet Akers, Kevin S
Schlotman, Taylor
Mangum, Lee C
Garcia, Gerardo
Wagner, Amanda
Seiler, Benjamin
Cartwright, Mark
Rifai, Sami
Ingber, Donald
Super, Michael
author_sort Akers, Kevin S
collection PubMed
description BACKGROUND: Infection is the leading cause of death among burn survivors, with sepsis associated with more extensive burns. Conventional diagnostic criteria are insensitive in this population. We examined a novel diagnostic ELISA based on Mannose-Binding Lectin (MBL) linked to an immunoglobulin Fc domain, which measures the concentration of Pathogen-Associated Molecular Patterns (PAMPs) across a broad range of bacterial and fungal organisms, for diagnosis and antimicrobial management of sepsis in burn patients. METHODS: We prospectively enrolled burn patients with ≥15% Total Body Surface Area (TBSA) burns into groups of noninfected, sepsis, or incipient infection, and healthy volunteers. Sepsis was defined by clinical actions responsive to sepsis. The FcMBL ELISA was performed daily using fresh whole blood. Burn subjects were sampled daily until completing antimicrobials, for 14 days if noninfected, and once for healthy controls. Differences in median PAMP concentrations between groups were assessed with the Kruskal–Wallis test, including multiple comparisons between categories. RESULTS: 14 burn patients (3 noninfected, of whom 1 died prior to sampling, 4 Sepsis, 7 Incipient) were enrolled. The median (25–75% CI) PAMP concentration was 0.53 (0.12–1.34) ng/mL in healthy controls, 3.725 (2.53–5.94) ng/mL in noninfected, 2.22 (1.42–4.62) ng/mL in incipient, and 1.59 (0.83–2.29) ng/mL in sepsis groups. PAMP concentrations in sepsis were different (P = 0.0057) from noninfected, but incipient did not differ from noninfected (P = 0.2025). The dynamic range was lower in healthy controls (2.69 ng/mL) than incipient (4.57 ng/mL), sepsis (4.70 ng/mL), or noninfected (5.90 ng/mL). PAMP elevations correlated with clinical deterioration from infection, and were not associated with OR visits for debridement and grafting. 7 of 11 infected patients had declining PAMP levels at completion of antimicrobial therapy. 2 subjects had PAMP elevations associated with Aspergillus molds in their burn wounds. CONCLUSION: The FcMBL ELISA assay may be useful for diagnosis of infection in burn patients, and may facilitate earlier discontinuation of antimicrobials. This assay may also have a novel utility for early diagnosis of Invasive Fungal Infection. DISCLOSURES: All authors: No reported disclosures.
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spelling pubmed-68111742019-10-29 653. Diagnosis of Burn Sepsis Using the FcMBL ELISA: A Pilot Study in Critically Ill Burn Patients Akers, Kevin S Schlotman, Taylor Mangum, Lee C Garcia, Gerardo Wagner, Amanda Seiler, Benjamin Cartwright, Mark Rifai, Sami Ingber, Donald Super, Michael Open Forum Infect Dis Abstracts BACKGROUND: Infection is the leading cause of death among burn survivors, with sepsis associated with more extensive burns. Conventional diagnostic criteria are insensitive in this population. We examined a novel diagnostic ELISA based on Mannose-Binding Lectin (MBL) linked to an immunoglobulin Fc domain, which measures the concentration of Pathogen-Associated Molecular Patterns (PAMPs) across a broad range of bacterial and fungal organisms, for diagnosis and antimicrobial management of sepsis in burn patients. METHODS: We prospectively enrolled burn patients with ≥15% Total Body Surface Area (TBSA) burns into groups of noninfected, sepsis, or incipient infection, and healthy volunteers. Sepsis was defined by clinical actions responsive to sepsis. The FcMBL ELISA was performed daily using fresh whole blood. Burn subjects were sampled daily until completing antimicrobials, for 14 days if noninfected, and once for healthy controls. Differences in median PAMP concentrations between groups were assessed with the Kruskal–Wallis test, including multiple comparisons between categories. RESULTS: 14 burn patients (3 noninfected, of whom 1 died prior to sampling, 4 Sepsis, 7 Incipient) were enrolled. The median (25–75% CI) PAMP concentration was 0.53 (0.12–1.34) ng/mL in healthy controls, 3.725 (2.53–5.94) ng/mL in noninfected, 2.22 (1.42–4.62) ng/mL in incipient, and 1.59 (0.83–2.29) ng/mL in sepsis groups. PAMP concentrations in sepsis were different (P = 0.0057) from noninfected, but incipient did not differ from noninfected (P = 0.2025). The dynamic range was lower in healthy controls (2.69 ng/mL) than incipient (4.57 ng/mL), sepsis (4.70 ng/mL), or noninfected (5.90 ng/mL). PAMP elevations correlated with clinical deterioration from infection, and were not associated with OR visits for debridement and grafting. 7 of 11 infected patients had declining PAMP levels at completion of antimicrobial therapy. 2 subjects had PAMP elevations associated with Aspergillus molds in their burn wounds. CONCLUSION: The FcMBL ELISA assay may be useful for diagnosis of infection in burn patients, and may facilitate earlier discontinuation of antimicrobials. This assay may also have a novel utility for early diagnosis of Invasive Fungal Infection. DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2019-10-23 /pmc/articles/PMC6811174/ http://dx.doi.org/10.1093/ofid/ofz360.721 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Akers, Kevin S
Schlotman, Taylor
Mangum, Lee C
Garcia, Gerardo
Wagner, Amanda
Seiler, Benjamin
Cartwright, Mark
Rifai, Sami
Ingber, Donald
Super, Michael
653. Diagnosis of Burn Sepsis Using the FcMBL ELISA: A Pilot Study in Critically Ill Burn Patients
title 653. Diagnosis of Burn Sepsis Using the FcMBL ELISA: A Pilot Study in Critically Ill Burn Patients
title_full 653. Diagnosis of Burn Sepsis Using the FcMBL ELISA: A Pilot Study in Critically Ill Burn Patients
title_fullStr 653. Diagnosis of Burn Sepsis Using the FcMBL ELISA: A Pilot Study in Critically Ill Burn Patients
title_full_unstemmed 653. Diagnosis of Burn Sepsis Using the FcMBL ELISA: A Pilot Study in Critically Ill Burn Patients
title_short 653. Diagnosis of Burn Sepsis Using the FcMBL ELISA: A Pilot Study in Critically Ill Burn Patients
title_sort 653. diagnosis of burn sepsis using the fcmbl elisa: a pilot study in critically ill burn patients
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811174/
http://dx.doi.org/10.1093/ofid/ofz360.721
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