Abstract

BackgroundInfection 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.MethodsWe 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.Results14 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.ConclusionThe 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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