Yield of clinical metagenomics: insights from real-world practice for tissue infections

Hui Tang; Yuqing Chen; Xinyan Tang; Muyun Wei; Juan Hu; Xuan Zhang; Dairong Xiang; Qing Yang; Dongsheng Han

doi:10.1016/j.ebiom.2024.105536

Yield of clinical metagenomics: insights from real-world practice for tissue infections

EBioMedicine. 2024 Dec 26:111:105536. doi: 10.1016/j.ebiom.2024.105536. Online ahead of print.

Authors

Hui Tang¹, Yuqing Chen², Xinyan Tang³, Muyun Wei⁴, Juan Hu⁵, Xuan Zhang⁶, Dairong Xiang⁶, Qing Yang⁷, Dongsheng Han⁸

Affiliations

¹ Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, PR China.
² Department of Laboratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, PR China; Zhejiang Key Laboratory of Clinical in Vitro Diagnostic Techniques, Hangzhou, 310003, PR China; Institute of Laboratory Medicine, Zhejiang University, Hangzhou, 310003, PR China.
³ Department of Laboratory Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
⁴ School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, 310053, PR China.
⁵ Department of Critical Care Units, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, PR China.
⁶ State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, PR China.
⁷ Department of Laboratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, PR China. Electronic address: [email protected].
⁸ Department of Laboratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, PR China; Zhejiang Key Laboratory of Clinical in Vitro Diagnostic Techniques, Hangzhou, 310003, PR China; Institute of Laboratory Medicine, Zhejiang University, Hangzhou, 310003, PR China. Electronic address: [email protected].

PMID: 39729886
DOI: 10.1016/j.ebiom.2024.105536

Abstract

Background: While metagenomic next-generation sequencing (mNGS) has been acknowledged as a valuable diagnostic tool for infections, its clinical validity and impact on patient management when using fresh tissue samples remains uncertain.

Methods: We conducted a retrospective cross-sectional study involving patients who underwent tissue mNGS at a tertiary hospital in China from February 2021 to February 2024, aiming to assess its ability to detect plausible pathogens and its clinical validity and impact.

Findings: A total of 520 mNGS results from 508 patients were analysed, detecting plausible pathogens in 302 (58.1%) tests, including 260 single-pathogen and 42 (13.9%) multi-pathogen results. Rare pathogens, such as Balamuthia mandrillaris, Bartonella henselae, and Sporothrix globosa, were identified. Of the multi-pathogen results, 22 were with predominance of anaerobes. mNGS showed higher positivity in cases with high initial suspicion of infection than those used for ruling out infection (PR 1.961, 95% CI: 1.604-2.394) and in patients living with HIV (PR 1.312, 95% CI: 1.047-1.643) or solid organ transplant recipients (PR 1.346, 95% CI: 1.103-1.643) compared to immunocompetent individuals. Sensitivity and specificity for diagnosing confirmed/probable infections were 85.0% (95% CI: 76.7%-93.3%) and 93.7% (95% CI: 86.8%-100.0%), respectively. mNGS influenced clinical management in 258 (49.6%) cases by identifying new infections and in 112 (21.5%) by excluding infections. It prompted initiation (20.2%), modification (23.1%), or discontinuation (6.3%) of antimicrobial therapy.

Interpretation: mNGS demonstrates high diagnostic accuracy for tissue infections. Its impact on clinical management highlights the need to integrate it into current diagnostic practices.

Funding: National Natural Science Foundation of China (No. 82472371), "Leading Geese" Research and Development Plan of Zhejiang Province (No. 2024C03218), and Pudong New Area Joint Project (PW2021D-09).

Keywords: Biopsy; Metagenomic; Next-generation sequencing; Tissue infection; mNGS.