Gene Sequencing Detected Infection 2x Better Than Culture

A new prospective study from 15 academic institutions has determined that next generation sequencing has the potential to detect infection causing organisms 2x better than culture and, thereby, dramatically increase the ability to reliably predict treatment failure due to periprosthetic joint infection (PJI).

Lubbock, Texas-based MicroGenDX, the High Complexity Laboratory utilized in the study, goes beyond detecting the presence of an infection and identifies the exact micro-organism(s) involved.

“PJI can be devastating, with numerous recent studies indicating that patients with PJI have a five-year mortality rate that matches and exceeds that of common cancers like breast, prostate and melanoma. We are sorely in need of a technology that can provide concrete, quantifiable improvements in patient care,” stated co-author Javad Parvizi, M.D., an orthopedic surgeon and the director of Clinical Research at the Rothman Orthopaedic Institute in Philadelphia. “With next generation sequencing, I believe we have found such a method.”

From the press release, “Typically, with an infected joint, surgeons remove the implant and either put in a new one at the same time (a one-stage exchange) or put in a new implant at a later date (a two-stage exchange). At the time of removal, a culture is taken in order to determine what organism caused the failure. In the event of a two-stage exchange, a culture is taken to see if any of the organism remains in the joint area.”

The problem, says Dr. Parvizi, is that following two-stage exchanges, 20-30% of the implants are re-infected. “We have been calling these ‘re-infections,’ but that is not entirely accurate. For 15 years, I have theorized that it is in fact multiple organisms that cause these infections. Cultures, when positive, usually identify the dominant organism and miss the others. They also often fail to identify unusual or slow-growing infective organisms in up to one out of three cases. In this study, we hypothesized that some of the later treatment failures are perhaps not re-infections, but rather infections due to organisms that have been present from the beginning—but not detected via traditional culture methods.”

The study, which lasted over two-and-a-half years, involved 851 total hip and knee revisions. The researchers wrote, “214 revisions were considered infected and 563 were aseptic. Overall, 139 patients failed by re-operation with an organism confirmed on culture. At the species level, the organisms present on culture at the time of failure were also present on initial next generation sequencing sampling at the time of revision 51.2% of the time. In contrast, culture results at revision detected microbes cultured at failure 19.51% of the time. Among International Consensus Meeting positive revisions, next generation sequencing detected the organism causing failure in 55.7% of cases (vs. 28.6% for culture).”

“At the genus level, next generation sequencing at revision detected the microbe at failure 67.5% of the time overall, and in 68.6% of International Consensus Meeting -positive revisions. Examination of negative next generation sequencing results demonstrated that 78.0% of next generation sequencing negative results were seen in International Consensus Meeting-negative cases. Among the 139 patients that failed treatment following revision, only 8.63% were next generation sequencing negative at revision.”

Co-investigator Karan Goswami, M.D. stated, “We found that around 20% of the revisions failed during the multicenter study period and, of those, we looked to see which organisms were involved. In the majority of cases (80-90%) that failed due to a supposedly new organism, next generation sequencing demonstrated that these organisms were actually in the joint at the time of the first-stage surgery.”

“Cultures are a comparatively primitive approach to isolating organisms,” states Dr. Parvizi. “Next generation sequencing provides us with faster and more accurate information so that we can get patients the correct treatment in a more timely manner. No longer will surgeons have to rely on guessing/deduction when it comes to which organisms they are contending with. Going forward, molecular techniques for the isolation of infected organism will soon become the standard of care in orthopedics.”