Characteristics of mycological criteria for the diagnosis of invasive mold infections in patients with severe burn injury

TL;DR

This study evaluates how different diagnostic methods for mold infections perform in patients with severe burns, finding that combining tests improves diagnosis and that more positive tests correlate with higher mortality.

Contribution

The study provides the first comprehensive assessment of mold diagnostic criteria in burn patients and identifies optimal diagnostic combinations.

Findings

Combining skin biopsies with plasma qPCR improves timely and reliable IFD diagnosis in burn patients.

Mortality increases with the number of positive diagnostic criteria and coexistence of multiple mold species.

Plasma qPCR detected 81.3% of Mucorales cases but only 15.4% of Fusarium cases with skin involvement.

Abstract

Invasive fungal diseases (IFDs) are common and often fatal in severe burn patients due to skin barrier loss and immune dysfunction. However, current definitions of invasive mold infections are poorly adapted to this population. This study evaluated the characteristics of various diagnostic criteria and their combinations in relation to clinical outcomes in burn patients. We conducted a retrospective cohort study of all patients admitted to the Burn ICU from 2014 to 2023 with ≥15% total burn surface area and at least one sample sent to the mycology lab. Criteria included direct microscopy, culture (respiratory, skin, or tissue), species-specific quantitative PCR (qPCR) (Aspergillus, Mucorales, and Fusarium) on plasma/tissue/bronchoalveolar lavage fluid, and serum galactomannan. Among 276 patients, 489/6,184 samples were positive, including 281 skin biopsies (direct examination and conventional culture) and 132 plasma specimens (qPCR). Positive diagnostic criteria ≥1 was found in 93 patients (33.7%): Aspergillus (25.7%), Mucorales (10.9%), and Fusarium (9.8%). Twenty-seven patients (9.8%) had ≥2 criteria involving ≥2 mold types. Mortality rose with the number of positive criteria: 12.7% (0), 10.7% (1, 2), 27.3% (3, 4), and 46.7% (≥5) (P < 0.001). Plasma qPCR was positive in 81.3% of Mucorales, 40% of Aspergillus, and 15.4% of Fusarium cases with skin involvement. Skin biopsies (direct examination and conventional culture) combined with species-specific plasma qPCR enhance timely and reliable IFD diagnosis in burn patients. Mortality correlated with the number of positive criteria and coexistence of multiple mold species, underscoring the need for broad antifungal coverage and the value of multi-criteria diagnostics to guide treatment.

Invasive mold infections are frequent and often fatal complications in patients with severe burns, occurring in up to 20% of cases with a total burn surface area exceeding 15%. Despite their severity, no standardized case definition currently exists to guide research or clinical management in this population. The performance of existing mycological diagnostic criteria remains unknown in burn patients. In this 10-year retrospective study, we evaluated the diagnostic performance of individual and combined mold-related criteria in relation to patient outcomes, analyzing more than 6,000 clinical samples. These findings provide a first comprehensive assessment of mold diagnostic markers in the burn population.

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