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

Author:

Akers Kevin S1,Schlotman Taylor1,Mangum Lee C1,Garcia Gerardo1,Wagner Amanda1,Seiler Benjamin2,Cartwright Mark2,Rifai Sami3,Ingber Donald4,Super Michael2

Affiliation:

1. US Army Institute of Surgical Research, JBSA Fort Sam Houston, Texas

2. Wyss Institute at Harvard University, Boston, Massachusetts

3. Wyss Institute for Biologically Inspired Engineering, Brookline, Massachusetts

4. Harvard University, Boston, Massachusetts

Abstract

Abstract 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.

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Oncology

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