Clinical Application of Metagenomic Next-Generation Sequencing of Microbial Cell-free DNA in Ruling Out Invasive...

Patients with severe thermal burns are highly susceptible to invasive fungal infections due to compromised skin integrity, prolonged hospitalization, and immunosuppression. Traditional diagnostic methods, such as cultures and tissue biopsies with histopathology, have limitations. Metagenomic next-generation sequencing (mNGS) of microbial cell-free DNA in plasma is a rapid, noninvasive diagnostic tool for detecting fungal elements in the bloodstream. The aim of this report is to present the utility of this method to aid in ruling out an invasive fungal infection in a patient with burns. This case involves a middle-aged male with extensive thermal burns who developed sepsis, with concerns of invasive fungal infection after fungal elements were detected in wound cultures of skin grafts. However, β-d-glucan and galactomannan assays were negative, and mNGS did not detect fungal DNA in plasma. Histopathological examination of tissue biopsies later confirmed the absence of angioinvasion, and blood cultures showed no evidence of fungemia. As a result, antifungal therapy was safely discontinued without clinical deterioration. While mNGS has shown potential for negative predictive value in immunocompromised patients, its role in patients with burns warrants further investigation. Integrating mNGS with conventional diagnostic methods may improve clinical decision-making, reduce unnecessary empirical antifungal treatment, and enhance patient outcomes.