Clinical utility of plasma microbial cell-free DNA sequencing in determining microbiologic etiology of infectious syndromes in solid organ transplant recipients

Background: Metagenomic next-generation sequencing (mNGS) is increasingly being used for microbial detection in various infectious syndromes. However, data regarding the use of mNGS in solid organ transplant recipients (SOTR) are lacking. Objectives: To describe and analyze real-world clinical impact of mNGS using plasma microbial cell-free DNA (mcfDNA) in SOTR. Design: Retrospectively reviewed all adult SOTR who underwent mNGS testing using plasma mcfDNA at Baylor St Luke’s Medical Center from March 2017 to February 2023. Methods: Clinical impact (positive, neutral, and negative) was assessed using standardized objective criteria. Three Infectious Diseases physicians independently performed clinical adjudication to determine the correlation of mcfDNA results with clinical diagnosis. A descriptive analysis of the patient and clinical characteristics was performed. Results: A total of 113 mcfDNA tests in liver (42%), kidney (35%), lung (20%) and heart (13%) transplant recipients were performed in the study period. The most common clinical syndromes were pneumonia (36%), fever of unknown origin (16%), and intra-abdominal infections (15%). Most (80, 71%) of the mcfDNA test results were positive for microorganisms. Twenty-seven (24%) cases were classified as positive clinical impact, 82 (73%) were neutral and 4 (3%) were negative, respectively. Conclusion: In SOTR, mcfDNA sequencing can add a positive clinical impact in a quarter of the cases and identify microorganisms beyond conventional microbiological testing across clinical syndromes. The negative clinical impact was rare. However, larger prospective studies are needed to define the optimal timing and utilization of mcfDNA in the sequence of diagnostic evaluation for syndrome-specific workup in SOTR. Summary: Metagenomic next-generation sequencing (mNGS) is a novel diagnostic tool that can identify difficult-to-detect microorganisms in SOTR. Our study demonstrates that the mNGS test resulted in a positive clinical impact in 1 out of 4 patients. Plain language summary Use of plasma cell-free DNA testing to diagnose microbiologic causes of infections in solid organ transplant recipients In our study, we evaluated the use of metagenomic next-generation sequencing (mNGS) in solid organ transplant patients who were hospitalized with concerns for infection that was difficult to diagnose by standard methods of testing. We reviewed 113 patients and found that the most common syndromes in which mNGS aided in diagn