The Pediatric infectious disease journal · 2025
Plasma Microbial Cell-free DNA Sequencing for the Detection of Kingella kingae Pediatric Spinal Infections.
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Ahmed Asim A, Park Sarah Y, Smollin Matthew J, Lindner Martin S, Sarmiento Clemente Adriana, Del Valle Penella Ana, Laufer P Marcelo, Sanchez-Vegas Carolina, Cotilla Manuel R, Melish Marian E, Trieu Connie, Kabani Nazia A, Cooper Joshua, Lloyd Audrey R, Kimberlin David W, Arnold John C, Jordan-Villegas Alejandro, Patterson Lori E, Foster Catherine E, Yagupsky Pablo
Аннотация
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.
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.