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Review
. 2021 Apr 1;6(4):236-244.
doi: 10.1302/2058-5241.6.200099. eCollection 2021 Apr.

Next generation sequencing for pathogen detection in periprosthetic joint infections

Pier F Indelli  1 , Stefano Ghirardelli  2 , Bruno Violante  2 , Derek F Amanatullah  1
Affiliations
Review

Next generation sequencing for pathogen detection in periprosthetic joint infections

Pier F Indelli et al. EFORT Open Rev. .

Abstract

Periprosthetic joint infections (PJI) represent one of the most catastrophic complications following total joint arthroplasty (TJA). The lack of standardized diagnostic tests and protocols for PJI is a challenge for arthroplasty surgeons.Next generation sequencing (NGS) is an innovative diagnostic tool that can sequence microbial deoxyribonucleic acids (DNA) from a synovial fluid sample: all DNA present in a specimen is sequenced in parallel, generating millions of reads. It has been shown to be extremely useful in a culture-negative PJI setting.Metagenomic NGS (mNGS) allows for universal pathogen detection, regardless of microbe type, in a 24-48-hour timeframe: in its nanopore-base variation, mNGS also allows for antimicrobial resistance characterization.Cell-free DNA (cfDNA) NGS, characterized by lack of the cell lysis step, has a fast run-time (hours) and, together with a high sensitivity and specificity in microorganism isolation, may provide information on the presence of antimicrobial resistance genes.Metagenomics and cfDNA testing have reduced the time needed to detect infecting bacteria and represent very promising technologies for fast PJI diagnosis.NGS technologies are revolutionary methods that could disrupt the diagnostic paradigm of PJI, but a comprehensive collection of clinical evidence is still needed before they become widely used diagnostic tools. Cite this article: EFORT Open Rev 2021;6:236-244. DOI: 10.1302/2058-5241.6.200099.

Keywords: PJI; next generation sequencing; periprosthetic joint infections.

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Conflict of interest statement

ICMJE Conflict of interest statement: PFI reports consultancy for Exactech and grants/grants pending from Zimmer Biomet, all outside the submitted work. SG reports employment as an attending surgeon by Istituto Clinico Sant’ambrogio, Milan, Italy, outside the submitted work. BV reports consultancy for Smith & Nephew and Exactech, employment by Istituto Clinico Sant’Ambrogio, IRCCS Galeazzi, Milan, Italy, payment for lectures including service on speakers bureaus by Smith & Nephew and Lima Orthopaedics, royalties from Lima Orthopaedics, and stock/stock options in Stryker Corporation and Zimmer Biomet, all outside the submitted work. DFA reports grants from NIH-NCATS and OREF, related to PJI, not NGS, related to the submitted work, and consultancy for Stryker, Exactech, Depuy, Zimmer- Biomet, Haraeus and Medcura, expert testimony for the Expert Institute, grants from NIH-NCATS and OREF, payment for manuscript preparation from Medscape, patents owned by Arthology Consulting, Arthrology Designs and Stanford, royalties from Exactech, and stock/stock options in nSight Surgical, QT Ultrasound and Recoup Fitness, all unrelated to the submitted work.

Figures

Fig. 1
Fig. 1
Next generation sequencing (NGS) workflow for periprosthetic joint infection (PJI) diagnosis.
Fig. 2
Fig. 2
Metagenomic next generation sequencing (mNGS) workflow.
Fig. 3
Fig. 3
Cell-free DNA (cfDNA) next generation sequencing (NGS) workflow.
See this image and copyright information in PMC

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