Molecular sequencing technologies in the diagnosis and management of prosthetic joint infections

ABSTRACT

Introduction

Prosthetic joint infections (PJIs) can be challenging to eradicate and have high morbidity and mortality. Current microbiology culture methods can be associated with a high false-negative rate of up to 50%. Early and accurate diagnosis is crucial for effective treatment, and negative results have been linked to a greater rate of reoperation.

Areas covered

There has been increasing investigation of the use of next-generation sequencing (NGS) technology such as metagenomic shotgun sequencing to help identify causative organisms and decrease the uncertainty around culture-negative infections. The clinical importance of the organisms detected and their management, however, requires further study. The polymerase chain reaction (PCR) has shown promise, but in recent years multiple studies have reported similar or lower sensitivity for bacteria detection in PJIs when compared to traditional culture. Furthermore, issues such as high cost and complexity of sample preparation and data analysis are to be addressed before it can move further toward routine clinical practice.

Expert opinion

Metagenomic NGS has shown results that inspire cautious optimism – both in culture-positive and culture-negative cases of joint infection. Refinement of technique could revolutionize the way PJIs are diagnosed, managed, and drastically improve outcomes from this currently devastating complication.

KEYWORDS:

• Biofilm
• culture-negative
• diagnosis
• metagenomics
• molecular
• next-generation sequencing
• pcr
• prosthetic joint infection

Article highlights

• Joint replacement is a successful orthopedic procedure that is expected to rise due to an increasing and aging population, but complications may arise due to prosthetic joint infection (PJI), which accounts for high morbidity and mortality.

• Diagnosis is proving to be a real challenge as there is no ‘gold standard’ diagnostic method and relies upon a combination of methods. This, along with various definitions, no standard diagnostic criteria, and culture-negative results due to biofilm-associated microorganisms and previous antimicrobial use makes diagnosis difficult.

• Currently, conventional culture is the main diagnostic method in clinical settings, but the process takes a long time and with culture-negative results.

• There is increasing potential of molecular technologies in the diagnosis of prosthetic joint infections such as polymerase chain reaction (PCR), specifically broad-range polymerase chain reaction (BR-PCR) and metagenomic next-generation sequencing (mNGS) that allow for culture-independence.

• BR-PCR shows promise, but there is limited clinical use.

• As a powerful molecular tool, mNGS is increasingly being applied to infectious disease diagnostics and provides direct identification of all DNA/RNA in patient samples, identifies unknown pathogens and sequences the whole genome rapidly with high accuracy, sensitivity and specificity. This technique is a useful adjunct and has been compared to BR-PCR in the context of prosthetic joint infection diagnosis.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.