Total joint arthroplasty continues to gain acceptance as the standard of care for the treatment of severe degenerative joint disease, and is considered one of the most successful surgical interventions in the history of medicine. However, infection of these implants, called periprosthetic joint infection (PJI), remains one of the biggest challenges facing orthopaedics today. PJI can lead to additional surgeries, revision, fusion, amputation, and possibly even death.
PJI is relatively uncommon after shoulder replacement, but is still a problematic complication which is more common after revision arthroplasty and, according to some reports, after Reverse shoulder arthroplasty. The pathogenesis of PJI involves a complex series of interactions between the implant, the patient’s immune system and the offending microorganisms. Only a small number of microorganisms are needed to seed the implant. Such organisms adhere to the implant and form a biofilm, which protects the organisms from detection, conventional antimicrobial agents and the host’s immune system.
PJI is on the rise for many reasons including an increasing number of comorbidities in patients undergoing the procedure, with higher rates of obesity, diabetes, and cardiovascular disease contributing to a greater risk of infection. The microorganisms responsible for PJI are becoming more resistant to treatment. Staphylococcal species account for 50-65% ofall PJI cases throughout the world and are the most common causative pathogens, and in some institutions, MRSA is the causative pathogen in more than half of PJI cases. In the shoulder, in particular, propionibacterium acne is causative, and often unassociated with signs of infection and difficult to culture. This agent may only cause pain, thus an index of suspicion must exist.
It is important to accurately diagnose PJI because its management differs from that of other causes of arthroplasty failure. The most common symptom of PJI is pain. In acute infection, the local signs and symptoms (e.g., severe pain, swelling, erythema, and warmth at the infected joint) of inflammation are generally present. On the other hand, chronic infection usually has a more subtle presentation, with pain alone, and is often accompanied by loosening of the prosthesis at the bone-implant interface . The diagnosis of PJI has proven quite challenging, as both acute and chronic infections can be difficult to differentiate from other forms of inflammation.Thus far, the reported literature on the diagnosis of PJI has focused on and evaluated laboratory tests that were never developed specifically for the diagnosis of PJI. These include the erythrocyte sedimentation rate (ESR), the serum C-reactive protein (CRP), the synovial fluid white blood cell count and the leukocyte differential.
The Musculoskeletal Infection Society (MSIS) has published a consensus statement in response to the inconsistencies regarding the diagnosis of PJI, aiming to provide a unified definition of PJI for both clinical practice and research publication.erential have been shown to vary significantly between institutions . The full MSIS criteria are listed below:
Based on the proposed criteria, a definite diagnosis of PJI can be made when the following conditions are met:
1. A sinus tract communicating with the prosthesis; or
2. A pathogen is isolated by culture from two separate tissue or fluid samples obtained from the affected prosthetic joint; or
3. Four of the following six criteria exist:
a. Elevated serum erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) concentration
b. Elevated synovial white blood cell (WBC) count
c. Elevated synovial neutrophil percentage (PMN%)
d. Presence of purulence in the affected joint
e. Isolation of a microorganism in one culture of periprosthetic tissue or fluid
f. Greater than five neutrophils per high-power field in five high-power fields observed from histologic analysis of periprosthetic tissue at 400 times magnification.
The currently utilized diagnostic tests such as ESR, serum CRP, cultures, and WBC count generally have a sensitivity or specificity for PJI that is less than 90%. And most of the studies demonstrating these diagnostic values excluded patients with systemic inflammatory diseases and patients on antibiotics, which may comprise 10-30% of the population tested.
Correctly diagnosing the group of patients with PJI requires a test with a high sensitivity.Correctly identifying a patient who is not infected is equally important, requiring a test with a high specificity. Inflammatory diseases can affect both the systemic tests and local synovial fluid tests, resulting in falsely elevated values.
The Synovasure™ Test for Periprosthetic Joint Infection (PJI) (see attached PDF) leverages diagnostic capabilities of synovial fluid biomarkers.
These biomarkers include inflammatory proteins, cytokines, and antimicrobial peptides that are known to be involved in the host response to infection.
CD Diagnostics has embarked on a very comprehensive synovial fluid biomarker evaluation program and identified 5 synovial fluid biomarkers that had an area under the curve (AUC) of 1.0, with a specificity of 100% and sensitivity of 100%. The proteins with antimicrobial function outperformed the cytokine biomarkers. The alpha-defensin protein, human neutrophil elastase 2, the bactericidal/permeability increasing protein, the neutrophil gelatinase-associated lipocalin, and lactoferrin were able to predict the MSIS diagnosis in all study patients. The alpha-defensin protein provided the best overall diagnostic characteristics in this study, when considering the needs of developing a diagnostic test. In the setting of PJI, alpha-defensin reaches concentrations above 5.2 mg/L, with a mean concentration of 65 mg/L. These concentrations are ideal for development of an immunoassay diagnostic test.
Synovasure™ test for PJI has indeed been commercially developed, and requirs a sample of synovial fluid. For more information you can read the attached PDF from Zimmer
PJI is relatively uncommon after shoulder replacement, but is still a problematic complication which is more common after revision arthroplasty and, according to some reports, after Reverse shoulder arthroplasty. The pathogenesis of PJI involves a complex series of interactions between the implant, the patient’s immune system and the offending microorganisms. Only a small number of microorganisms are needed to seed the implant. Such organisms adhere to the implant and form a biofilm, which protects the organisms from detection, conventional antimicrobial agents and the host’s immune system.
PJI is on the rise for many reasons including an increasing number of comorbidities in patients undergoing the procedure, with higher rates of obesity, diabetes, and cardiovascular disease contributing to a greater risk of infection. The microorganisms responsible for PJI are becoming more resistant to treatment. Staphylococcal species account for 50-65% ofall PJI cases throughout the world and are the most common causative pathogens, and in some institutions, MRSA is the causative pathogen in more than half of PJI cases. In the shoulder, in particular, propionibacterium acne is causative, and often unassociated with signs of infection and difficult to culture. This agent may only cause pain, thus an index of suspicion must exist.
It is important to accurately diagnose PJI because its management differs from that of other causes of arthroplasty failure. The most common symptom of PJI is pain. In acute infection, the local signs and symptoms (e.g., severe pain, swelling, erythema, and warmth at the infected joint) of inflammation are generally present. On the other hand, chronic infection usually has a more subtle presentation, with pain alone, and is often accompanied by loosening of the prosthesis at the bone-implant interface . The diagnosis of PJI has proven quite challenging, as both acute and chronic infections can be difficult to differentiate from other forms of inflammation.Thus far, the reported literature on the diagnosis of PJI has focused on and evaluated laboratory tests that were never developed specifically for the diagnosis of PJI. These include the erythrocyte sedimentation rate (ESR), the serum C-reactive protein (CRP), the synovial fluid white blood cell count and the leukocyte differential.
The Musculoskeletal Infection Society (MSIS) has published a consensus statement in response to the inconsistencies regarding the diagnosis of PJI, aiming to provide a unified definition of PJI for both clinical practice and research publication.erential have been shown to vary significantly between institutions . The full MSIS criteria are listed below:
Based on the proposed criteria, a definite diagnosis of PJI can be made when the following conditions are met:
1. A sinus tract communicating with the prosthesis; or
2. A pathogen is isolated by culture from two separate tissue or fluid samples obtained from the affected prosthetic joint; or
3. Four of the following six criteria exist:
a. Elevated serum erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) concentration
b. Elevated synovial white blood cell (WBC) count
c. Elevated synovial neutrophil percentage (PMN%)
d. Presence of purulence in the affected joint
e. Isolation of a microorganism in one culture of periprosthetic tissue or fluid
f. Greater than five neutrophils per high-power field in five high-power fields observed from histologic analysis of periprosthetic tissue at 400 times magnification.
The currently utilized diagnostic tests such as ESR, serum CRP, cultures, and WBC count generally have a sensitivity or specificity for PJI that is less than 90%. And most of the studies demonstrating these diagnostic values excluded patients with systemic inflammatory diseases and patients on antibiotics, which may comprise 10-30% of the population tested.
Correctly diagnosing the group of patients with PJI requires a test with a high sensitivity.Correctly identifying a patient who is not infected is equally important, requiring a test with a high specificity. Inflammatory diseases can affect both the systemic tests and local synovial fluid tests, resulting in falsely elevated values.
The Synovasure™ Test for Periprosthetic Joint Infection (PJI) (see attached PDF) leverages diagnostic capabilities of synovial fluid biomarkers.
These biomarkers include inflammatory proteins, cytokines, and antimicrobial peptides that are known to be involved in the host response to infection.
CD Diagnostics has embarked on a very comprehensive synovial fluid biomarker evaluation program and identified 5 synovial fluid biomarkers that had an area under the curve (AUC) of 1.0, with a specificity of 100% and sensitivity of 100%. The proteins with antimicrobial function outperformed the cytokine biomarkers. The alpha-defensin protein, human neutrophil elastase 2, the bactericidal/permeability increasing protein, the neutrophil gelatinase-associated lipocalin, and lactoferrin were able to predict the MSIS diagnosis in all study patients. The alpha-defensin protein provided the best overall diagnostic characteristics in this study, when considering the needs of developing a diagnostic test. In the setting of PJI, alpha-defensin reaches concentrations above 5.2 mg/L, with a mean concentration of 65 mg/L. These concentrations are ideal for development of an immunoassay diagnostic test.
Synovasure™ test for PJI has indeed been commercially developed, and requirs a sample of synovial fluid. For more information you can read the attached PDF from Zimmer
