A Cell-Free DNA Plasma Next-Generation Sequencing Test—Is It Worth the Cost?

Background: The Karius Test (KT), a microbial cell-free DNA next-generation sequencing assay, is increasingly utilized in challenging infectious syndromes. However, its real-world clinical utility and cost-effectiveness remain uncertain. Methods: We conducted a retrospective review of 88 KT results from adult patients at UC San Diego Health between July 2017 and April 2024. Each case was evaluated for clinical impact using standardized criteria. We analyzed diagnostic yield, turnaround time, number needed to test (NNT), and institutional billing data for reimbursement and cost implications. Results: Of 88 unique tests, forty-nine (55.7%) identified at least one pathogen. Eleven (12.5%) had a positive clinical impact—eight provided the only microbiologic diagnosis, and three were faster than conventional methods. Vascular/graft infections showed the highest yield. Twenty-one tests had a neutral impact; fifty-six showed no clinical benefit. The Median turnaround time was 3 days. The NNT was 6.1 or 2.75 including neutral cases. Cost analysis revealed a substantial financial burden without transparent reimbursement mechanisms in inpatient settings. Conclusion: The KT demonstrates modest clinical utility with noteworthy benefits in select scenarios. Given its high cost and variable impact, we advocate for diagnostic stewardship led by infectious disease specialists to optimize test use and minimize unnecessary expense.