Novel Diagnostics in Revision Arthroplasty: Implant Sonication and Multiplex Polymerase Chain Reaction

Abstract

In orthopedic patients, foreign body-associated infections, especially periprosthetic joint infections (PJIs), are a devastating complication of arthroplasty. Infection requires complex treatment, may result in long hospitalization and causes considerable costs. Multiple surgical revisions can be necessary in these patients, with a loss in function as well as in quality of life.The routine preoperative diagnostics include blood examination for C-reactive protein (CRP) and other biomarkers, as well as joint aspirate analysis for cell count, differentiation, and culture. Intraoperative specimens for histology and microbiology are also standard procedure. The microbiological examination of removed implants with sonication, in combination with the implementation of molecular biology techniques in microbiology, represent two novel techniques currently employed to enhance the differential diagnostics of PJI.We present here the step-wise procedure of analyzing joint aspirate and sonication fluid, using a cartridge-based multiplex polymerase chain reaction (PCR) system. Results were matched against conventional cultures and consensus criteria for PJI. Conventional microbiological cultures from tissue biopsies, joint aspirate and sonication fluid showed a sensitivity of 66.7%, 66.7%, and 88.9%, respectively, and a specificity of 82.3%, 54.6%, and 61.5%, respectively. The PCR diagnostic of the sonication fluid and the joint fluid showed a sensitivity of 50.0% and 55.6%, respectively, and both a specificity of 100.0%. Both PCR diagnostics combined had a sensitivity of 66.7% and a specificity of 100.0%. The multiplex PCR therefore presents a rapid diagnostic tool with moderate sensitivity but high specificity in diagnosing PJI.

How reliable is the next generation of multiplex-PCR for diagnosing prosthetic joint infection compared to the MSIS criteria? Still missing the ideal test

“…Renz et al 23 combined the mPCR with the sonication of synovial fluid and found a sensitivity of 51% and a specificity of 94% respectively. Similar results were found by Hischebeth et al 24 presenting a sensitivity of 66.7% and a specificity of 100%. In their study mPCR and fluid sonication were also investigated together.…”

2018 International Consensus Meeting on Musculoskeletal Infection: Research Priorities from the General Assembly Questions

“…However, these biomarkers only identify the presence or absence of infection, and do not specify the particular offending organism or its antibiotic sensitivities. Some diagnostic techniques which may improve the ability to detect organisms, which are difficult to isolate or culture and potentially provide information on antibiotic resistance genes, include PCR, next‐generation sequencing and prosthesis sonication . While some preliminary data exists on all of these techniques, there is concern regarding the fact that the increased sensitivity may come at the cost of a higher false‐positive rate, and focused research is needed in this area.…”

New developments and future challenges in prevention, diagnosis, and treatment of prosthetic joint infection

“…From these results, the authors suggested that if implant sonication is feasible in a particular clinic, it should be included in the diagnosis workflow as it has superior ability to recover the infecting organism. Alternatively, sonicate fluid can be analyzed using multiplex PCR methods in order to determine the infecting organisms without the need for culture 103 . The addition of molecular diagnosis by PCR may improve the accuracy of sonicate fluid because it has the ability to identify viable and nonviable bacteria as well as decreasing the overall time to diagnose from days to hours 104 .…”

“…Alternatively, sonicate fluid can be analyzed using multiplex PCR methods in order to determine the infecting organisms without the need for culture. 103 The addition of molecular diagnosis by PCR may improve the accuracy of sonicate fluid because it has the ability to identify viable and nonviable bacteria as well as decreasing the overall time to diagnose from days to hours. 104 Ultimately, future studies are warranted to achieve consensus on the use of sonication in the clinic.…”