Diagnostic Role of Metagenomic Next-Generation Sequencing in Tubercular Orthopedic Implant-Associated Infection

Abstract

Objective

The diagnosis of tubercular orthopedic implant-associated infection (TB-IAI) is challenging. This study evaluated the value of metagenomic next-generation sequencing (mNGS) for the diagnosis of TB-IAI and developed a standardized diagnostic procedure for TB-IAI.

Methods

The records of all patients with TB-IAI diagnosed and treated at our institution between December 2018 and September 2022 were retrospectively reviewed. Patient demographic characteristics, medical history, laboratory test, microbial culture, histopathology, and mNGS results, and time to diagnosis were recorded. The diagnostic efficiency of mNGS for TB-IAI was assessed by comparing the results and diagnostic time with that of other diagnostic modalities.

Results

Ten patients were included in the analysis, including eight with prosthetic joint infections and two with fracture-related infections. The mNGS positivity rate was 100% (10/10), which was higher than that of TB-antibody (11%, 1/9), real-time quantitative polymerase chain reaction (22%, 2/9), T-SPOT.TB (25%, 2/8), purified protein derivative (50%, 4/8), microbial culture (50%, 5/10), and histopathology (20%, 2/10). mNGS shortened the time to diagnosis of TB-IAI. A standardized diagnostic procedure for TB-IAI was developed based on the findings.

Conclusion

mNGS is useful for the diagnosis of TB-IAI. mNGS is recommended in cases where it is difficult to identify a pathogen using routine diagnostic tests. The standardized diagnostic procedure might improve TB-IAI diagnosis.

Importance

TB-IAI is a rare infection, which occurs after orthopedic surgery and hard to diagnose microbiologically. mNGS is a new detection technique not yet discussed in current literature as a means for TB-IAI diagnostics. Here we describe a cohort of patients with TB-IAI diagnosed by mNGS show high efficiency of mNGS for detection of this pathology and present a clinical algorithm supplementing conventional methods for TB-IAI assessment.

Keywords:

• metagenomic next-generation sequencing
• implant-associated infection
• Mycobacterium tuberculosis complex
• orthopedic infection
• diagnosis

Ethical Approval Statement

This study was approved by the ethics committee of Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China and complied with the requirements of the Declaration of Helsinki. All patients consented to the surgical and diagnostic procedures. Due to the retrospective nature of this study, the ethics committee of Shanghai Sixth People’s Hospital waived the requirement for informed consent for inclusion in the analysis.

Acknowledgments

We are grateful to the Department of Clinical Laboratory of Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine for providing us with the pathogen information of the patients. We thank BGI Genomics, China, for performing the mNGS testing and the bioinformatics analysis.

Disclosure

The authors declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work.

Additional information

Funding

This work received no specific funding.