Published in the June issue of Journal of Bone and Joint Surgery, "An Enhanced Understanding of Culture-Negative Periprosthetic Joint Infection with Next-Generation Sequencing" compared two infection detection technologies head-to-head: standard culture and next-generation sequencing (NGS). The study found NGS reliably detected potential pathogens in over two-thirds of culture-negative patients who met ICM PJI infection criteria.  The study is the largest of its kind, with over 300 infected participants across top orthopedic institutions that included the Rothman Institute of Orthopedics, Cleveland Clinic, and Rush University Medical Center.

From June 2016 to August 2020, samples were taken from patients meeting ICM PJI infection criteria, and the samples were tested using both culture and NGS. The traditional method of diagnosing a suspected periprosthetic joint infection (PJI) combines culture with immune response biomarkers. However, the study indicated that culture had a "no growth" failure rate of more than 28% for patients with PJI, providing no useful guidance to physicians. The study then evaluated NGS results from the culture-negative 28%. NGS found one or more pathogens in 56 of the 81 culture-negative cases, with 91% returning polymicrobial results (at least two different species detected). 

Periprosthetic joint infection is a dangerous infection. With a higher mortality rate than prostate cancer, melanoma, or breast cancer, PJI presents a significant health risk to those with knee or hip replacements. And with over one million total hip and total knee replacement procedures performed each year in the United States, an infection rate of 1.5% leaves thousands of patients at risk of death or amputation when revision surgeries fail. 

"This study, the result of four years of extensive collaborative research between numerous high-caliber institutions in the U.S., has revealed that next-generation sequencing is indeed a very promising technology for identification of infective pathogens in joint infections. This is a major step forward for the medical community in taking care of patients with a very challenging condition." - Javad Parvizi, MD, PRCS

This study demonstrated that the newer molecular technique of next-generation DNA sequencing overcame the challenge of organisms failing to grow in culture by using sample DNA to identify bacteria and fungi that may be causing infection. NGS provided a more comprehensive picture of the microbial profile of infection that is often missed by traditional culture, and demonstrated that a majority of infections are in fact polymicrobial. This multi-center study paves the way for additional studies to compare patient outcomes when NGS or culture are used for PJI diagnosis and treatment. 

About Javad Parvizi, MD, FRCS

Dr. Parvizi holds the James Edwards chair of orthopedics at Sidney Kimmel Medical School in Philadelphia. He is an active orthopedic surgeon with interest in management of orthopedic infections. He has published over 800 peer-reviewed articles, numerous textbooks and has been the recipient of grants from the NIH, DOD, OREF, and numerous other funding bodies for his work in orthopedic infections. He serves as scientific advisor to MicroGenDX.

About MicroGenDX

Founded in 2008, MicroGenDX has become the industry leader in rapid turnaround and affordability for comprehensive Next-Generation Sequencing (NGS) and qPCR testing for clinical diagnostics. MicroGenDX is CLIA-licensed and CAP-accredited, and has been the trusted research partner for the CDC, U.S. Army, NASA and the FDA. MicroGenDX has published over 70 clinical studies and is the most experienced molecular diagnostic laboratory with some 1.5 million samples processed. This multicenter study was funded by MicroGenDX.

References

https://pubmed.ncbi.nlm.nih.gov/35726882/

https://orthoinfo.aaos.org/en/diseases--conditions/joint-replacement-infection/ 

https://hcup-us.ahrq.gov/reports/projections/2012-03.pdf