Marisa H Miceli

Metagenomic next-generation sequencing (mNGS) of cell-free DNA is an emerging modality for the diagnosis of infectious diseases, but studies on its clinical utility are limited. We conducted a retrospective single-center study including all patients who had plasma mNGS sent at the University of Michigan between 1 January 2021 and 25 July 2022. Test results were assessed for clinical impact. A total of 71 tests were sent on 69 patients; the mean ± SD age was 52 ± 19 years; and 35% of patients were immunocompromised. Forty-five (63%) mNGS test results were positive and 14 (31%) had clinical impact—from starting new antimicrobials (n = 7), discontinuing antimicrobials (n = 4), or changing antimicrobial duration (n = 2) or by affecting surgical decision making (n = 1). Twenty-six (37%) mNGS test results were negative and only 4 (15%) were impactful, leading to discontinuation of antimicrobials. Overall, just 25% of mNGS tests were clinically relevant. There was no significant difference in the proportion of tests that were clinically relevant between negative and positive results (P = .16) or if patients were immunocompromised (P = .57). Plasma mNGS was most frequently impactful (in 50% of patients) when included in the diagnostic workup of cardiovascular infection but less impactful in other clinical syndromes, including fever of unknown origin and pulmonary infection. Our findings underscore the need to further study this testing modality, particularly with prospective research including negative controls, before it is considered for widespread use.