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用于检测金氏金杆菌小儿脊髓感染的血浆微生物无细胞DNA测序

Plasma Microbial Cell-free DNA Sequencing for the Detection of Kingella kingae Pediatric Spinal Infections.

作者信息

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

机构信息

From the Division of Infectious Diseases, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts.

Medical Affairs, Karius, Inc., Redwood City, California.

出版信息

Pediatr Infect Dis J. 2025 Jun 1;44(6):582-588. doi: 10.1097/INF.0000000000004743. Epub 2025 Feb 21.

DOI:10.1097/INF.0000000000004743
PMID:39999355
原文链接:
https://pmc.ncbi.nlm.nih.gov/articles/PMC12058358/
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.

摘要

背景

由于金氏金杆菌的苛求特性,其骨骼系统感染的诊断颇具挑战性。通过Karius检测(一种商业宏基因组测序检测)对血浆中循环微生物游离DNA(mcfDNA)进行检测和定量,可能为诊断由难培养微生物(如金氏金杆菌)引起的小儿脊柱感染带来希望。

方法

回顾2018年4月至2020年12月期间金氏金杆菌血浆mcfDNA测序检测结果,以确定儿科(年龄<18岁)患者。对患有脊柱感染的患者的病历进行回顾,并将mcfDNA测序的诊断性能与常规护理检测(即培养、聚合酶链反应)进行比较。

结果

在7家机构中识别出10例患有金氏金杆菌脊柱感染的儿童。中位年龄为16.5个月(范围11 - 23个月)。所有病例患者均患有椎体骨髓炎,其中9例患有脊椎间盘炎。与常规护理检测相比,mcfDNA测序的敏感性显著更高(麦克尼马尔检验6.25,双侧P = 0.0133)。它是9例患者唯一的微生物学诊断方法,从样本采集到得出结果的中位时间为2.5天(范围2 - 5天)。5例病例患者中,尽管进行了抗生素预处理,但仍检测到金氏金杆菌mcfDNA。9名儿童接受了针对病原体的抗菌治疗。

结论

血浆mcfDNA测序提供了一种快速、非侵入性的方法来检测导致小儿脊柱感染的金氏金杆菌。这种不依赖培养的方法可能有助于诊断,尽管进行了抗生素预处理,随后还能进行靶向治疗,并可能避免活检的需要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f015/12058358/c914b395a95c/inf-44-0582-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f015/12058358/c914b395a95c/inf-44-0582-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f015/12058358/c914b395a95c/inf-44-0582-g001.jpg

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本文引用的文献

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Microorganisms. 2023 Aug 22;11(9):2130. doi: 10.3390/microorganisms11092130.
3
Plasma Microbial Cell-Free DNA Sequencing from over 15,000 Patients Identified a Broad Spectrum of Pathogens.
对超过 15000 名患者的血浆微生物无细胞 DNA 进行测序,鉴定出了广谱病原体。
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