Next generation sequencing for pathogen detection in periprosthetic joint infections

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.