Plasma Microbial Cell-free DNA Sequencing for the Detection of Kingella kingae Pediatric Spinal Infections
Year: 2025
Type: article
Abstract: BACKGROUND: Diagnosis of Kingella kingae skeletal system infections is made challenging by the microbe's fastidious nature. Detection and quantification of circulating microbial cell-free DNA (mcfDNA) in plasma by the Karius Test, a commercial metagenomic sequencing test, may offer promise in diagnosing pediatric spinal infections caused by difficult-to-culture organisms such as K. kingae . METHODS: Plasma mcfDNA sequencing detections of K. kingae from April 2018 to December 2020 were reviewed to identify pediatric (age <18 years) patients. Medical charts of those with spinal infections were reviewed, and mcfDNA sequencing diagnostic performance was compared with usual care tests (ie, cultures, polymerase chain reaction). RESULTS: Ten children with K. kingae spinal infections were identified across 7 institutions. The median age was 16.5 months (range 11-23 months). All case-patients had vertebral osteomyelitis with 9 having spondylodiscitis. Compared with usual care tests, mcfDNA sequencing was significantly more sensitive (McNemar's test 6.25, 2-tailed P = 0.0133). It was the only method of microbiological diagnosis in 9 patients, providing results in a median of 2.5 days (range 2-5 days) from sample collection. K. kingae mcfDNA was detected despite antibiotic pretreatment in 5/5 case-patients. Pathogen-tailoring of antimicrobial coverage was undertaken in 9 children. CONCLUSION: Plasma mcfDNA sequencing offers a rapid, noninvasive method of detecting K. kingae causing pediatric spinal infections. This culture-independent approach may facilitate diagnosis, despite antibiotic pretreatment and subsequently targeted therapy and potentially obviate the need for biopsy.
Authors: Asim A. Ahmed, Sarah Y. Park, Matthew J. Smollin, Martin S. Lindner, Adriana Sarmiento Clemente, Ana Del Valle Penella, P. Marcelo Laufer, Carolina Sanchez-Vegas, Manuel R. Cotilla, Marian E. Melish, Connie Trieu, Nazia A. Kabani, Joshua Cooper, Audrey R. Lloyd, David W. Kimberlin, John C. Arnold, Alejandro Jordan-Villegas, Lori E. Patterson, Catherine E. Foster, Pablo Yagupsky
Institutions: Boston Children's Hospital, Karius, Inc. (United States), Arkansas Children's Hospital, Miami Children's Hospital, Kapiolani Medical Center for Women and Children, University of Florida Health, University of Florida, University of Alabama at Birmingham, Rady Children's Hospital-San Diego, Arnold Palmer Hospital for Children, East Tennessee Children's Hospital, Baylor College of Medicine, Texas Children's Hospital, Ben-Gurion University of the Negev, Soroka Medical Center
Language: English
Subfield: Clinical Biochemistry
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W4407932826