Improving the accuracy of synovial fluid analysis in the diagnosis of prosthetic joint infection with simple and inexpensive biomarkers

2017 ◽  
Vol 99-B (3) ◽  
pp. 351-357 ◽  
Author(s):  
R. Sousa ◽  
P. Serrano ◽  
J. Gomes Dias ◽  
J. C. Oliveira ◽  
A. Oliveira
Keyword(s):  
Synovial Fluid ◽  
Prosthetic Joint Infection ◽  
Joint Infection ◽  
Fluid Analysis ◽  
Synovial Fluid Analysis ◽  
Prosthetic Joint

Comparison of molecular diagnosis with serum markers and synovial fluid analysis in patients with prosthetic joint infection

2018 ◽  
Vol 100-B (10) ◽  
pp. 1345-1351 ◽  
Author(s):  
F-C. Kuo ◽  
Y-D. Lu ◽  
C-T. Wu ◽  
H-L. You ◽  
G-B. Lee ◽  
...  
Keyword(s):  
Sequence Analysis ◽  
Synovial Fluid ◽  
Molecular Diagnosis ◽  
Prosthetic Joint Infection ◽  
Joint Infection ◽  
28S Rrna ◽  
Rt Pcr ◽  
Fluid Analysis ◽  
Prosthetic Joint ◽  
Polymicrobial Infections

Aims The aim of this study was to compare the results of 16S/28S rRNA sequencing with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and synovial fluid analysis in the diagnosis of prosthetic joint infection (PJI). Patients and Methods Between September 2015 and August 2016, 214 consecutive patients were enrolled. In the study population, there were 25 patients with a PJI and 189 controls. Of the PJI patients, 14 (56%) were women, and the mean age at the time of diagnosis was 65 years (38 to 83). The ESR and CRP levels were measured, and synovial fluid specimens were collected prospectively. Synovial fluid was subjected to reverse transcription polymerase chain reaction (RT-PCR)/sequence analysis targeting the 16S/28S rRNA, and to conventional culture. Laboratory personnel who were blind to the clinical information performed all tests. The diagnosis of PJI was based on the criteria of the Musculoskeletal Infection Society. Results A total of 25 patients had a confirmed PJI. In 20 cases of monomicrobial PJI, the PCR products could be perfectly matched with the 16S/28S rRNA genes specific for different species of bacteria provided by sequence analysis. Of the five polymicrobial cases of PJI, 16S/28S rRNA PCR sequence analysis failed to identify the concordant bacteria species. In the 189 control patients, there was one false-positive RT-PCR result. The sensitivity and specificity of the molecular diagnosis method were 100% (95% confidence interval (CI) 85.7 to 100) and 99.5% (95% CI 97.1 to 99.9), respectively, whereas the positive and negative predictive values of PCR were 96.1% (95% CI 79.6 to 99.9) and 100% (95% CI 98.1 to 100), respectively. The PCR results were significantly better than serological diagnostic methods (p = 0.004 and p = 0.010 for ESR and CRP, respectively), the synovial fluid white blood cell (WBC) count (p = 0.036), and percentage of polymorphonuclear cells (PMN%) (p = 0.014). Conclusion Stepwise RT-PCR and sequence analysis of the 16S/28S rRNA carried out under stringent laboratory conditions achieved highly sensitive and specific results for the differentiation between aseptic and septic joints undergoing arthroplasty. Sequence analysis successfully identified bacterial strains in monomicrobial infections but failed to identify molecular targets in polymicrobial infections. Further refinement of the protocols to identify the bacteria in polymicrobial infections is needed. Cite this article: Bone Joint J 2018;100-B:1345–51.

Diagnostic accuracy of alpha-defensin enzyme-linked immunosorbent assay in the clinical evaluation of painful hip and knee arthroplasty with possible prosthetic joint infection

2019 ◽  
Vol 101-B (8) ◽  
pp. 970-977 ◽  
Author(s):  
S. Kleiss ◽  
N. M. Jandl ◽  
A. Novo de Oliveira ◽  
W. Rüther ◽  
A. Niemeier
Keyword(s):  
Synovial Fluid ◽  
Diagnostic Accuracy ◽  
Immunosorbent Assay ◽  
Knee Arthroplasty ◽  
Prosthetic Joint Infection ◽  
Joint Infection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Coagulase Negative Staphylococci ◽  
Predictive Values ◽  
Prosthetic Joint

Aims The aim of this study was to evaluate the diagnostic accuracy of the synovial alpha-defensin enzyme-linked immunosorbent assay (ELISA) for the diagnosis of prosthetic joint infection (PJI) in the work-up prior to revision of total hip (THA) and knee arthroplasty (TKA). Patients and Methods Inclusion criteria for this prospective cohort study were acute or chronic symptoms of the index joint without specific exclusion criteria. Synovial fluid aspirates of 202 patients were analyzed and semiquantitative laboratory alpha-defensin ELISA was performed. Final diagnosis of PJI was established by examination of samples obtained during revision surgery. Results Sensitivity and specificity of the alpha-defensin ELISA for PJI were 78.2% (95% confidence interval (CI) 66.7 to 88.5) and 96.6% (95% CI 93.0 to 99.3). Positive and negative predictive values were 89.6% (95% CI 80.6 to 97.8) and 92.2% (95% CI 87.5 to 96.1). The test remained false-negative in 22% of septic revisions, most of which were due to coagulase-negative staphylococci all occurring in either late-chronic or early-postoperative PJI. Conclusion The routine use of synovial fluid alpha-defensin laboratory ELISA in the preoperative evaluation of symptomatic THAs and TKAs is insufficient to accurately diagnose PJI. Particularly in cases involving low-virulence organisms, such as coagulase-negative staphylococci, there remains a need for tests with a higher sensitivity. Cite this article: Bone Joint J 2019;101-B:970–977.

scholarly journals Evaluation of a rapid lateral flow calprotectin test for the diagnosis of prosthetic joint infection

2019 ◽  
Author(s):  
Alexander J. Trotter ◽  
Rachael Dean ◽  
Celia E. Whitehouse ◽  
Jarle Mikalsen ◽  
Claire Hill ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Sensitivity And Specificity ◽  
Prosthetic Joint Infection ◽  
Predictive Value ◽  
Joint Infection ◽  
Lateral Flow ◽  
Lateral Flow Assay ◽  
Prosthetic Joint ◽  
Flow Test ◽  
Lateral Flow Test

AbstractBackgroundMicrobiological diagnosis of prosthetic joint infection (PJI) relies on culture techniques that are slow and insensitive. Rapid tests are urgently required to improve patient management. Calprotectin is a neutrophil biomarker of inflammation that has been demonstrated to be effective for the diagnosis of PJI. A calprotectin based lateral flow test has been developed for the rapid detection of PJI using synovial fluid samples.MethodsA convenience series of 69 synovial fluid samples from patients at the Norfolk and Norwich University Hospitals (NNUH) were collected intraoperatively from 52 hip and 17 knee revision operations. Calprotectin levels were measured using a new commercially available lateral flow assay for PJI diagnosis (Lyfstone). For all samples, synovial fluid was pipetted onto the lateral flow device and the signal was read using a mobile phone app after 15 minutes incubation at room temperature.ResultsAccording to the Musculoskeletal Infection Society (MSIS) criteria, 24 patients were defined as PJI positive and the remaining 45 were negative. The overall accuracy of the lateral flow test against the MSIS criteria was 75%. The test had a sensitivity and specificity of 75% and 76% respectively with a positive predictive value (PPV) of 62% and a negative predictive value (NPV) of 85%. Discordant results were then reviewed by the clinical team using available patient data to develop an alternative gold standard for defining presence/absence of infection (MSIS+). Compared to MSIS+, the test showed an overall accuracy of 83%, sensitivity and specificity of 95% and 78% respectively, a PPV of 62% and an NPV of 98%. Test accuracy for hip revisions was 77% and for knee revisions was 100%.ConclusionsThis study demonstrates that the calprotectin lateral flow assay is an effective diagnostic test for PJI. Our data suggests that the test is likely to generate false positive results in patients with metallosis and gross osteolysis.

scholarly journals Metagenomic next-generation sequencing of synovial fluid demonstrates high accuracy in prosthetic joint infection diagnostics

2020 ◽  
Vol 9 (7) ◽  
pp. 440-449 ◽  
Author(s):  
Zida Huang ◽  
Wenbo Li ◽  
Gwo-Chin Lee ◽  
Xinyu Fang ◽  
Li Xing ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Synovial Fluid ◽  
Prosthetic Joint Infection ◽  
Joint Infection ◽  
High Accuracy ◽  
Next Generation ◽  
Primary Arthroplasty ◽  
Prosthetic Joint ◽  
Culture Positive ◽  
Generation Sequencing

Aims The aim of this study was to evaluate the performance of metagenomic next-generation sequencing (mNGS) in detecting pathogens from synovial fluid of prosthetic joint infection (PJI) patients. Methods A group of 75 patients who underwent revision knee or hip arthroplasties were enrolled prospectively. Ten patients with primary arthroplasties were included as negative controls. Synovial fluid was collected for mNGS analysis. Optimal thresholds were determined to distinguish pathogens from background microbes. Synovial fluid, tissue, and sonicate fluid were obtained for culture. Results A total of 49 PJI and 21 noninfection patients were finally included. Of the 39 culture-positive PJI cases, mNGS results were positive in 37 patients (94.9%), and were consistent with culture results at the genus level in 32 patients (86.5%) and at the species level in 27 patients (73.0%). Metagenomic next-generation sequencing additionally identified 15 pathogens from five culture-positive and all ten culture-negative PJI cases, and even one pathogen from one noninfection patient, while yielding no positive findings in any primary arthroplasty. However, seven pathogens identified by culture were missed by mNGS. The sensitivity of mNGS for diagnosing PJI was 95.9%, which was significantly higher than that of comprehensive culture (79.6%; p = 0.014). The specificity is similar between mNGS and comprehensive culture (95.2% and 95.2%, respectively; p = 1.0). Conclusion Metagenomic next-generation sequencing can effectively identify pathogens from synovial fluid of PJI patients, and demonstrates high accuracy in diagnosing PJI. Cite this article: Bone Joint Res 2020;9(7):440–449.

scholarly journals The value of calprotectin in synovial fluid for the diagnosis of chronic prosthetic joint infection

2020 ◽  
Vol 9 (8) ◽  
pp. 450-456
Author(s):  
Zeyu Zhang ◽  
Yuanqing Cai ◽  
Guochang Bai ◽  
Chaofan Zhang ◽  
Wenbo Li ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Sensitivity And Specificity ◽  
Prosthetic Joint Infection ◽  
Joint Infection ◽  
White Blood Cells ◽  
Area Under The Curve ◽  
Enzyme Linked Immunosorbent Assay ◽  
Polymorphonuclear Cells ◽  
Diagnostic Efficacy ◽  
Prosthetic Joint

Aims This study aimed to evaluate calprotectin in synovial fluid for diagnosing chronic prosthetic joint infection (PJI) . Methods A total of 63 patients who were suspected of PJI were enrolled. The synovial fluid calprotectin was tested by an enzyme-linked immunosorbent assay (ELISA). Laboratory test data, such as ESR, CRP, synovial fluid white blood cells (SF-WBCs), and synovial fluid polymorphonuclear cells (SF-PMNs), were documented. Chi-squared tests were used to compare the sensitivity and specificity of calprotectin and laboratory tests. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was calculated to determine diagnostic efficacy. Results The median calprotectin level was 776 μg/ml (interquartile range (IQR) 536.5 to 1132) in the PJI group and 54.5 μg/ml (IQR, 38.75 to 78.25) in the aseptic failure (AF) group (p < 0.05). Using a threshold of 173 ug/ml, the sensitivity was 95.2%, with a 97.6% specificity, and the AUC was 0.993. The sensitivity of calprotectin of the antibiotic-treated PJI group was 100% versus 90.9% of the non-antibiotic-treated PJI group. Although 47.6% (ten cases) of the patients in the PJI group received antibiotics before aspiration, the diagnostic efficacy of calprotectin was not affected. The sensitivity and specificity of ESR, CRP, SF-WBCs, and SF-PMNs ranged from 76.2% to 90.5% and 64.3% to 85.7%, respectively. Conclusion Calprotectin in synovial fluid has great diagnostic efficacy for PJI diagnosisand outperformed ESR, CRP, SF-WBCs, and SF-PMNs. Cite this article: Bone Joint Res 2020;9(8):450–456.

Evaluation of synovial fluid neutrophil CD64 index as a screening biomarker of prosthetic joint infection

2020 ◽  
Vol 102-B (4) ◽  
pp. 463-469 ◽  
Author(s):  
Leilei Qin ◽  
Ning Hu ◽  
Xinyu Li ◽  
Yuelong Chen ◽  
Jiawei Wang ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Prosthetic Joint Infection ◽  
Bacterial Infections ◽  
Joint Infection ◽  
Polymorphonuclear Neutrophils ◽  
Musculoskeletal Infection ◽  
Neutrophil Cd64 ◽  
Prosthetic Joint ◽  
Significant Difference ◽  
Aseptic Failure

Aims Prosthetic joint infection (PJI) remains a major clinical challenge. Neutrophil CD64 index, Fc-gamma receptor 1 (FcγR1), plays an important role in mediating inflammation of bacterial infections and therefore could be a valuable biomarker for PJI. The aim of this study is to compare the neutrophil CD64 index in synovial and blood diagnostic ability with the standard clinical tests for discrimination PJI and aseptic implant failure. Methods A total of 50 patients undergoing revision hip and knee arthroplasty were enrolled into a prospective study. According to Musculoskeletal Infection Society (MSIS) criteria, 25 patients were classified as infected and 25 as not infected. In all patients, neutrophil CD64 index and percentage of polymorphonuclear neutrophils (PMN%) in synovial fluid, serum CRP, ESR, and serum CD64 index levels were measured preoperatively. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were analyzed for each biomarker. Results Serum CD64 index showed no significant difference between the two groups (p = 0.091). Synovial fluid CD64 index and PMN% discriminated good differentiation between groups of PJI and aseptic failure with AUC of 0.946 (95% confidence interval (CI) 0.842 to 0.990) and 0.938 (95% CI 0.832 to 0.987) separately. The optimal threshold value of synovial CD64 index for the diagnosis of PJI was 0.85, with a sensitivity of 92.00%, a specificity of 96.00%, and diagnostic odds ratio (DOR) of 227.11. Conclusion The present study demonstrates that CD64 index in synovial fluid could be a promising laboratory marker for screening PJI. The cut-off values of 0.85 for synovial CD64 index has the potential to distinguish aseptic failure from PJI. Cite this article: Bone Joint J 2020;102-B(4):463–469.

scholarly journals Two-stage exchange Arthroplasty is a viable treatment for Periprosthetic joint infection in inflammatory diseases

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Qiao Jiang ◽  
Jun Fu ◽  
Wei Chai ◽  
Li-Bo Hao ◽  
Yong-Gang Zhou ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Inflammatory Diseases ◽  
Joint Infection ◽  
Treatment Success ◽  
Serum Markers ◽  
Control Group ◽  
Two Stage ◽  
Fluid Analysis ◽  
Exchange Arthroplasty ◽  
Prosthetic Joint

Abstract Background Inflammatory diseases are chronic autoimmune systemic autoimmune diseases, which may increase the risk of prosthetic joint infection (PJI) after total joint arthroplasty (TJA). However, to our best knowledge, few studies have studied the association between inflammatory diseases and subsequent failure after two-stage exchange reimplantation. The aims of this study were to identify the differences in (1) serum markers, synovial indicators and pathology results and (2) treatment outcomes following two-stage exchange arthroplasty between patients with or without inflammatory diseases. Methods A retrospective review of 184 patients with PJI who underwent two-stage revision from 2014 to 2018 was conducted. PJI was diagnosed by using the MSIS criteria. Serum biomarkers, synovial fluid, organism and pathology results at the time of the PJI diagnosis and reimplantation were compared between patients with or without inflammatory diseases. Treatment success was defined according to the Delphi-based consensus criteria; Kaplan-Meier survivorship curves of the patients were generated and compared. Results There was no difference in the biomarkers, pathology results or organism profile at the time of the PJI diagnosis. At reimplantation, the patients with inflammatory diseases generally had higher values of serum markers than those without inflammatory diseases. However, synovial white blood cell count was comparable in patients with inflammatory diseases (1142.8 ± 1385.3*109/mL) and group C (1315.8 ± 1849.3*109/mL, p = 0.841). The total treatment success rate was 91.3% (92% for individuals with inflammatory diseases and 91.2% for the controls). The survivorship of the inflammatory disease group was comparable with that of the control group. Conclusion Two-stage exchange arthroplasty is a viable option for PJIs with inflammatory diseases. Synovial fluid analysis may be less affected by inflammatory diseases than serum markers did in the diagnosis persistent infection at reimplantation.

scholarly journals Synovial Fluid-Induced Aggregation Occurs across Staphylococcus aureus Clinical Isolates and is Mechanistically Independent of Attached Biofilm Formation

2021 ◽  
Author(s):  
Amelia Staats ◽  
Peter W. Burback ◽  
Mostafa Eltobgy ◽  
Dana M. Parker ◽  
Amal O. Amer ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Synovial Fluid ◽  
Prosthetic Joint Infection ◽  
Orthopedic Surgery ◽  
Biofilm Formation ◽  
Bacterial Infections ◽  
Joint Infection ◽  
Synovial Joint ◽  
Prosthetic Joint ◽  
Induced Aggregation

Bacterial infections of hip and knee implants are rare but devastating complications of orthopedic surgery. Despite a widespread appreciation of the considerable financial, physical, and emotional burden associated with the development of a prosthetic joint infection, the establishment of bacteria in the synovial joint remains poorly understood.

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