{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T06:19:49Z","timestamp":1787552389701,"version":"build-2736575974"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012547","name":"Natural Science Foundation of Guangxi Zhuang Autonomous Region","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012547","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Spinal infection (SI) remains diagnostically challenging because of heterogeneous etiologies, nonspecific clinical manifestations, and the limited sensitivity of conventional microbiological approaches, particularly following empirical antimicrobial exposure. Although metagenomic next-generation sequencing (mNGS) enables unbiased pathogen detection, its incremental clinical value beyond pathogen identification and its role within integrated diagnostic strategies remain incompletely established.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed 208 consecutive patients with suspected SI between August 2022 and August 2025. Final diagnoses were established using a multidisciplinary-adjudicated composite reference standard incorporating clinical, radiological, microbiological, and histopathological evidence. The diagnostic performance of mNGS was compared with conventional culture and histopathology. Furthermore, multimodal predictive models integrating clinical variables and microbiological information were developed using L1-regularized logistic regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the comparative cohort, mNGS achieved a significantly higher diagnostic yield than culture (66.5% vs. 27.41%,\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001). Among confirmed SI cases, mNGS demonstrated higher sensitivity than conventional culture (91.67% vs. 40.15%,\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001). mNGS identified a substantially broader pathogen spectrum, ranging from fastidious organisms such as\n                      <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                      and\n                      <jats:italic>Brucella<\/jats:italic>\n                      to rare pathogens including\n                      <jats:italic>Talaromyces marneffei<\/jats:italic>\n                      and\n                      <jats:italic>Coxiella burnetii<\/jats:italic>\n                      , and maintained robust sensitivity (98.2%) despite prior antibiotic exposure. While an integrated clinical model achieved an AUC of 0.916, mNGS as a standalone modality provided superior discriminative power (AUC = 0.889) compared to histopathology (AUC = 0.836), the Conventional Biomarker Model (AUC = 0.742), and culture (AUC = 0.693).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>mNGS is a high-yield diagnostic tool for spinal infection, particularly in culture-negative and antibiotic-pretreated scenarios. Integrating mNGS into a multimodal clinical framework facilitates etiological clarity and precision antimicrobial therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1904634","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T05:32:59Z","timestamp":1787549579000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrating metagenomic next-generation sequencing into a multimodal diagnostic framework for spinal infection: enhancing etiological identification and clinical prediction"],"prefix":"10.3389","volume":"16","author":[{"given":"Heng","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Spinal Orthopedics, The Second Affiliated Hospital of Guangxi Medical University, University East Road, Nanning","place":["Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyuan","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Spinal Orthopedics, The Second Affiliated Hospital of Guangxi Medical University, University East Road, Nanning","place":["Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Spinal Orthopedics, The Second Affiliated Hospital of Guangxi Medical University, University East Road, Nanning","place":["Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyu","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Spinal Orthopedics, The Second Affiliated Hospital of Guangxi Medical University, University East Road, Nanning","place":["Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xulin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Spinal Orthopedics, The Second Affiliated Hospital of Guangxi Medical University, University East Road, Nanning","place":["Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaojun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Spinal Orthopedics, The Second Affiliated Hospital of Guangxi Medical University, University East Road, Nanning","place":["Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoming","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Spinal Orthopedics, The Second Affiliated Hospital of Guangxi Medical University, University East Road, Nanning","place":["Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanming","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Spinal Orthopedics, The Second Affiliated Hospital of Guangxi Medical University, University East Road, Nanning","place":["Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-026-09806-3","article-title":"Clinical utility of metagenomic next-generation sequencing in diagnosing spinal infections: a systematic review and meta-analysis","volume":"35","author":"Alrasheed","year":"2026","journal-title":"Eur. Spine J"},{"key":"B2","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.idc.2017.01.003","article-title":"Infections of the spine","volume":"31","author":"Babic","year":"2017","journal-title":"Infect. Dis. Clinics North. America"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.12968\/hmed.2021.0448","article-title":"Spondylodiscitis in adults: diagnosis and management","volume":"83","author":"Baryeh","year":"2022","journal-title":"Br. J. Hosp. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e26","DOI":"10.1093\/cid\/civ482","article-title":"2015 infectious diseases society of america (IDSA) clinical practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults","volume":"61","author":"Berbari","year":"2015","journal-title":"Clin. Infect. 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