Background: Metagenomic next-generation sequencing (mNGS) is a novel diagnostic tool increasingly used in the field of infectious diseases. Little guidance is available regarding its appropriate use in different patient populations and clinical syndromes. We aimed to review the clinical utility of mNGS in patients with a specific clinical syndrome and identify factors that may increase its utility.
Methods: We retrospectively reviewed charts of 72 non-immunocompromised adults hospitalized with the clinical syndrome of 'fever of undetermined origin' and underwent mNGS testing. Standardized criteria from a previously published study were used to determine the clinical impact of mNGS testing. We applied logistic regression to identify factors associated with a positive clinical impact.
Results: Of the 72 patients identified, 62.5% were males with a median age of 56. All patients had a fever at the time of evaluation. At least one organism was identified in 65.3% of cases; most commonly were Epstein-Barr virus (13.9%), cytomegalovirus (12.5%), and Rickettsia typhi (11.1%). Of those determined to have an infectious etiology of their febrile syndrome, 89.5% (n = 34/38) had a positive mNGS. Consistency between the organism(s) on mNGS and the clinically determined infectious etiology was 82.4%. mNGS had a positive clinical impact in 40.3% of cases, a negative impact in 2.8%, and no impact in 56.9% of cases. Besides age, we did not identify other factors associated with a higher likelihood of positive clinical impact.
Conclusion: In our review, mNGS had a positive clinical impact in a large proportion of adults with fever of undetermined origin, with minimal negative impact. However, mNGS results should be interpreted carefully given the high rate of detection of pathogens of unclear clinical significance. Randomized clinical trials are needed to assess the clinical utility of this novel diagnostic tool.
Keywords: antimicrobial stewardship; diagnostic stewardship; fever of undetermined origin; next-generation sequencing.
Clinical utility of metagenomic next-generation sequencing in fever of undetermined origin In this study, we evaluated the use of a new diagnostic tool, namely, metagenomic next generation sequencing (mNGS), in hospitalized, non-immunocompromised, adult patients with a fever that was otherwise unexplained. We reviewed the clinical utility of this tool in 72 patients and found that at least one organism was found in 65.3% of cases, with the 2 most common organisms being viruses. In patients who were found to have an infection as the cause of their fever, 89.5% had a positive mNGS study. In 82.4% of cases, the infectious organism(s) found on mNGS was the organism thought to be the cause of the fever. Based on definitions from another study, mNGS had a positive clinical impact in 40.3% of cases, a negative impact in 2.8%, and no impact in 56.9% of cases. This study suggests that mNGS has minimal negative impact and can be a useful tool in identifying a causative infectious organism in patients with unexplained fevers. Additional studies are needed to identify patients and clinical conditions that would most benefit from this tool.
© The Author(s), 2024.