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Orthopedic Infections and Treatments · Journal article
Journal of International Medical Research · September 1, 2026
Encouraging direction, but not yet definitive.
This single-center retrospective study demonstrates that CT-guided tissue biopsy combined with metagenomic next-generation sequencing achieves high pathogen detection (91.0%) and sensitivity (94.7%) in blood culture-negative systemic infections, compared to conventional culture (55.1%). Antimicrobial therapy was modified in 69.2% of patients based on the sequencing results, suggesting clinical utility, but prospective validation and hard clinical outcome data are needed to establish practice-changing impact.
Single-center retrospective observational cohort study. Patients with suspected systemic infection meeting Sepsis-3 consensus criteria and negative conventional microbiological work-up (at least two sets of blood cultures), enrolled from a single center.. Intervention: Computed tomography–guided percutaneous biopsy of radiologically identified infectious foci with concurrent conventional culture and metagenomic next-generation sequencing processing. Compared with: Conventional microbiological culture and final comprehensive clinical diagnosis as reference standard. n = 78. Single center (location not specified in text).
Metagenomic next-generation sequencing detection rate 91.0% (71/78) versus conventional culture 55.1% (43/78), p < 0.001 Sensitivity 94.7% (95% CI: 86.9–98.5), specificity 100.0% (95% CI: 29.2–100.0), positive predictive value 100.0% (95% CI: 94.9–100.0) Among 35 culture-negative specimens, sequencing established diagnosis in 28 cases (80.0%)
No hard clinical outcomes reported (mortality, morbidity, length of stay, or clinical cure rates); only diagnostic performance and therapy modification measured
Clinicians managing blood culture-negative systemic infections may consider CT-guided tissue biopsy with metagenomic sequencing to guide targeted antimicrobial therapy, particularly when conventional cultures remain negative despite clinical suspicion. However, the high negative predictive value of 42.9% warrants caution in ruling out infection based on negative sequencing results in this setting.
A single-center retrospective cohort of 78 patients with blood culture-negative infections shows CT-guided biopsy plus metagenomic sequencing achieves high pathogen detection (91%), but lacks a prospective design, concurrent control arm, and hard clinical outcome data to establish practice-changing impact.
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Clinicians managing blood culture-negative systemic infections may consider CT-guided tissue biopsy with metagenomic sequencing to guide targeted antimicrobial therapy, particularly when conventional cultures remain negative despite clinical suspicion. However, the high negative predictive value of 42.9% warrants caution in ruling out infection based on negative sequencing results in this setting.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Objective To evaluate the diagnostic efficacy of computed tomography–guided percutaneous biopsy combined with metagenomic next-generation sequencing in patients with blood culture-negative systemic infections and to assess the clinical impact of using this combined strategy for etiological confirmation and guidance of targeted antimicrobial therapy. Methods This single-center retrospective observational cohort study enrolled 78 patients who met the Sepsis-3 consensus criteria for suspected systemic infection and had negative conventional microbiological work-ups (at least two sets of blood cultures) between April 2022 and March 2025. All patients underwent computed tomography–guided biopsy of radiologically identified infectious foci, with specimens processed concurrently for conventional culture and metagenomic next-generation sequencing. Diagnostic performance was benchmarked against the final comprehensive clinical diagnosis, and the influence of metagenomic next-generation sequencing findings on antimicrobial therapy modification was analyzed. Sample size calculation, based on a prior study estimating an metagenomic next-generation sequencing detection rate of 85% (α = 0.05, β = 0.2), indicated a minimum of 68 cases; accordingly, 78 patients were enrolled. Results Computed tomography–guided biopsy was technically successful in all 78 patients (100%). The pathogen detection rate of metagenomic next-generation sequencing (91.0%, 71/78) was significantly higher than that of conventional culture (55.1%, 43/78; p < 0.001). Using the final clinical diagnosis as the reference standard, metagenomic next-generation sequencing achieved a sensitivity of 94.7% (95% confidence interval: 86.9–98.5), specificity of 100.0% (95% confidence interval: 29.2–100.0), positive predictive value of 100.0% (95% confidence interval: 94.9–100.0), and negative predictive value of 42.9% (95% confidence interval: 9.9–81.6). Among the 35 culture-negative specimens, metagenomic next-generation sequencing established a definitive microbiological diagnosis in 28 cases (80.0%) and detected polymicrobial infections in 11 cases (14.1% of the cohort). Antimicrobial therapy was rationally adjusted based on metagenomic next-generation sequencing results in 69.2% (54/78) of the patients. Conclusions The integration of computed tomography–guided precision biopsy with metagenomic next-generation sequencing offers a highly effective diagnostic approach for blood culture-negative systemic infections. This synergistic strategy improves etiological diagnosis by providing high-yield target specimens that enable comprehensive, unbiased pathogen screening, facilitates differentiation between infectious and non-infectious etiologies, and supplies critical evidence for guiding precision antimicrobial therapy. These findings highlight the growing role of interventional radiology in the contemporary framework of precision infectious disease management.
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