Zhirui Xue, Hongyan Li, Xianming Wang, Yuanqing Cai, Zida Huang, Wenbo Li, Yang Su, Zhaoyang Wu, Xinyu Fang, Wenming Zhang
mNGS serves as a promising diagnostic rescue tool for occult TB-OAI when conventional cultures are negative or misleading. While limited by sample size, these preliminary findings suggest mNGS effectively guides the transition from empirical to targeted anti-tuberculosis therapy and limits diagnostic delays.
PURPOSE: Diagnosing tuberculous osteoarticular infections (TB-OAI) remains challenging due to frequent false-negative or confounding conventional culture results. This study evaluated the diagnostic and therapeutic utility of metagenomic next-generation sequencing (mNGS) for occult TB-OAI in patients presenting with negative or misleading culture outcomes.
PATIENTS AND METHODS: We retrospectively analyzed 13 patients with confirmed TB-OAI, encompassing periprosthetic, fracture-related, and native joint infections. Patients were stratified by conventional culture results into strictly culture-negative (n=8) and culture-confounded (n=5; yielding non-mycobacterial organisms) groups. A composite reference standard of mNGS positivity combined with histopathological or clinical validation established the definitive diagnosis. We assessed diagnostic yield, therapeutic modifications, and clinical outcomes.
RESULTS: Conventional culture failed to identify Mycobacterium tuberculosis in all 13 cases (0% sensitivity) and yielded misleading non-mycobacterial flora in 5 cases (38.5%). Conversely, mNGS successfully identified the pathogen in 100% (13/13) of patients, corroborated by histopathology in all cases. Consequently, mNGS results changed clinical management from empirical antibiotics to targeted anti-tuberculosis therapy in all cases (100%). Postoperative erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels decreased significantly (P < 0.05). Over a mean follow-up of 17.5 ± 3.0 months, 12 patients achieved durable infection eradication. One patient experienced early recurrence requiring a two-stage revision, ultimately achieving successful infection control.
CONCLUSION: mNGS serves as a promising diagnostic rescue tool for occult TB-OAI when conventional cultures are negative or misleading. While limited by sample size, these preliminary findings suggest mNGS effectively guides the transition from empirical to targeted anti-tuberculosis therapy and limits diagnostic delays.