Test For Periprosthetic Joint Infection Research Articles

The James A. Rand Young Investigator’s Award: Keeping It Simple: Are all Musculoskeletal Infection Society Tests Useful to Diagnose Periprosthetic Joint Infection?

BackgroundCurrent data evaluating the clinical value and cost-effectiveness of advanced diagnostic tests for periprosthetic joint infection (PJI) diagnosis, including alpha-defensin and synovial C-reactive protein (CRP), is conflicting. This study aimed to evaluate the adequacy of preoperative and intraoperative PJI workups without utilizing these tests. MethodsThis retrospective analysis identified all patients who underwent revision total knee or hip arthroplasty (rTKA and rTHA, respectively) for suspected PJI between 2018 and 2020 and had a minimum follow-up of 2 years. Perioperative data and lab results were collected, and cases were dichotomized based on whether they met the 2018 Musculoskeletal Infection Society (MSIS) criteria for PJI. In total, 204 rTKA and 158 rTHA cases suspected of PJI were reviewed. ResultsNearly 100% of the cases were categorized as “infected” for meeting the 2018 MSIS criteria without utilization of alpha-defensin or synovial CRP (rTKA: n = 193, 94.6%; rTHA: n = 156, 98.7%). Most cases were classified as PJI preoperatively by meeting either the major MSIS or the combinational minor MSIS criteria of traditional lab tests (rTKA: n = 177, 86.8%; rTHA: n = 143, 90.5%). A subset of cases was classified as PJI by meeting combinational preoperative and intraoperative MSIS criteria (rTKA: 16, 7.8%; rTHA: 13, 8.2%). Only 3.6% of all cases were considered “inconclusive” using preoperative and intraoperative data. ConclusionsGiven the high rate of cases satisfying PJI criteria during preoperative workup using our available tests, the synovial alpha-defensin and synovial CRP tests may not be necessary in the routine diagnostic workup of PJI. We suggest that the primary PJI workup process should be based on a stepwise algorithmic approach with the most economical testing necessary to determine a diagnosis first. The use of advanced, commercialized, and costly biomarkers should be utilized only when traditional testing is indeterminate.

Finding the Optimal Screening Test for Periprosthetic Joint Infection: A Prospective Study

BackgroundNo single test has demonstrated absolute accuracy in the diagnosis of periprosthetic joint infection (PJI). Serological markers are often used as screening tools to avoid unnecessary joint aspiration in cases with a low probability of infection. This study aimed to determine the utility of standard-of-care serological tests as a screening tool for PJI in patients undergoing revision arthroplasty. MethodsThis prospective study enrolled 502 patients undergoing revision hip or knee arthroplasty between May 2017 and August 2021. A PJI was defined using a modified definition of the 2018 International Consensus Meeting criteria. Plasma D-dimer, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fibrinogen were measured preoperatively. There were 82 patients undergoing reimplantation who were excluded. Additionally, 8 patients who had an inconclusive International Consensus Meeting score were also excluded. Of the 412 included patients, 317 (76.9%) underwent revision for aseptic failure, and 95 (23.1%) had PJI. Receiver operating characteristic curves were used to assess the diagnostic utility of each serological test. A pairwise comparison with Bonferroni correction was performed to determine whether the differences in areas under the curve (AUCs) between the tests were significant. Additional analyses were performed to find the threshold for each test that offered 100% sensitivity, allowing it to be the optimal screening test. ResultsAll 4 serological markers, D-dimer (AUC 0.860, sensitivity 81.3%, specificity 81.7%), CRP (AUC 0.862, sensitivity 90.4%, specificity 70.0%), ESR (AUC 0.833, sensitivity 73.9%, specificity 85.2%), and fibrinogen (AUC 0.798, sensitivity 74.7%, specificity 75.4%), demonstrated comparable accuracy for the diagnosis of PJI (all P > .05). When maximizing sensitivity to 100%, D-dimer demonstrated the highest specificity (AUC 0.860, specificity 40.2%), outperforming ESR (AUC 0.833, specificity 3.3%), fibrinogen (AUC 0.798, specificity 2.3%), and CRP (AUC 0.862, specificity 0%). A plasma D-dimer level of ≥ 244 ng/mL was identified as the optimal cutoff for use as a screening test. ConclusionsAlthough plasma D-dimer demonstrated similar diagnostic accuracy as CRP, ESR, and fibrinogen, it outperformed all 3 aforementioned serological markers when used as a screening test for PJI. Level of EvidenceLevel II.

Common inflammatory markers in the screening of knee arthroprosthesis infections

<p><strong>Aim<br /></strong> To evaluate the sensitivity and specificity of serum C-reactive protein (CRP) in early and late total knee arthroplasty (TKA)<br />infections.<br /><strong>Methods<br /></strong> Blood tests to determine CRP levels (cut-off 10 mg/L) were conducted before surgery, at 1st day, 7th day and 15th day after surgery and at 1, 3, 6,12, 24 and 36 months. Patients had routine follow-up visits and radiological evaluations at 14 days and at 1, 3, 6, 12, 24 and 36 months. Infections were recorded and classified according to Widmer classification. The χ2 test or Fisher (in subgroups smaller than 10 patients) exact test was used to compare categorical variables. The statistical significance was set at p < 0.05.<br /><strong>Results<br /></strong> A total of 19 infections were diagnosed during the followup. According to Widmer, five were classified as early post-operative and 14 as late chronic. All patients with early infections had suspected symptoms such as fever, swelling and pain. During the first month, 59 patients who had high CRP level but negative microbiological culture were considered as false positive representing a CRP sensitivity of 80% and a specificity of 67.6%. Fourteen patients had late chronic infection.<br /><strong>Conclusion<br /></strong> This study suggests that a synovial fluid aspiration should be performed in patients with persistent inflammation<br />symptoms with or without radiographic signs of loosening. Moreover, it recommends the use of different serum and synovial tests for periprosthetic joint infection (PJI) diagnosis.</p>

Physician Use of Multiple Criteria to Diagnose Periprosthetic Joint Infection May Be Less Accurate Than the Use of an Individual Test.

Introduction Multiple-criterion scoring systems for periprosthetic joint infection (PJI) can be algorithmically implemented in research, diagnostically outperforming individual tests. This improved performance may be lost in the practice setting, where clinicians rarely utilize strict algorithms. The ability of physicians to interpret multiple criteria for PJI and confront the complexity of combining them into a final diagnosis has never been studied. This study assessed the diagnostic characteristics of physicians using multiple criteria to diagnose PJI and compared the physicians' diagnostic accuracy to that of individual tests. Methods A total of 12 physicians, including academic arthroplasty surgeons (N=4), community arthroplasty surgeons (N=4), and infectious disease (ID) specialists (N=4) were asked to use their routine clinical diagnostic practice to assign a diagnosis to 277 clinical vignettes using multiple preoperative laboratory criteria for PJI. The undecided rate, interobserver agreement, and accuracy of physicians were characterized relative to the 2013 Musculoskeletal Infection Society (MSIS) gold standard and compared to the accuracy of each individual laboratory test for PJI. Results Physicians interpreting multiple criteria for PJI demonstrated high undecided diagnosis rates (mean=23.5%), poor interobserver agreement (kappa range=0.49-0.63), and mean accuracy of 90.8% (range:85.8%-97.4%) compared to the 2013 MSIS gold standard. The group of academic arthroplasty surgeons had a lower rate of undecided diagnoses than community arthroplasty surgeons (16.2% vs. 29.1%; p<0.0001) or ID specialists (16.2% vs. 25.1%; p<0.0001). Academic arthroplasty surgeons also exhibited a higher interobserver agreement than community arthroplasty surgeons (kappa = 0.63 (95%CI:0.59-0.68) vs. 0.49 (95%CI:0.44-0.54)). Mean physician accuracy (90.8%) was inferior to the alpha-defensin laboratory test (96.0%;p=0.0034) and the alpha-defensin lateral-flow test (94.6%;p=0.036), comparable to synovial fluid white blood cells (SF-WBC) (93.3%;p=0.17) and synovial fluid polymorphonuclear cell % (SF-PMN%) (94.0%;p=0.11), and superior to the erythrocyte sedimentation rate (ESR) (86.2%;p<0.0001) and C-reactive protein (CRP) (84.6%;p<0.0001). Only two academic arthroplasty surgeons in this study were able to outperform every individual test for PJI by combining multiple criteria to make a diagnosis. Conclusion Although multiple-criterion scoring systems may outperform individual tests for diagnosing PJI in the research setting, it appears that the complexity of using multiple tests to diagnose PJI causes indecision and variability among physicians. Physician use of multiple preoperative criteria to diagnose PJI is less accurate than the strict algorithmic calculation of the diagnosis as achieved in research. In fact, most physicians in this study would have improved their diagnostic accuracy for PJI by simply utilizing a single good test to make the diagnosis, instead of trying to combine multiple tests into a decision. We propose that less complex diagnostic criteria should be explored for routine clinical utilization.

Reliable Diagnostic Tests and Thresholds for Preoperative Diagnosis of Non-Inflammatory Arthritis Periprosthetic Joint Infection: A Meta-analysis and Systematic Review.

The current diagnostic criteria for periprosthetic joint infection (PJI) are diverse and controversial, leading to delayed diagnosis. This study aimed to evaluate and unify their diagnostic accuracy and the threshold selection of serum and synovial routine tests for PJI at an early stage. We searched the MEDLINE and Embase databases for retrospective or prospective studies which reported preoperative-available assays (serum, synovial, or culture tests) for the diagnosis of chronic PJI among inflammatory arthritis (IA) or non-IA populations from January 1, 2000 to June 30, 2022. Threshold effective analysis was performed on synovial polymorphonuclear neutrophils (PMN%), synovial white blood cell (WBC), serum C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) to find the relevant cut-offs. Two hundred and sixteen studies and information from 45,316 individuals were included in the final analysis. Synovial laboratory-based α-defensin and calprotectin had the best comprehensive sensitivity (0.91 [0.86-0.94], 0.95 [0.88-0.98]) and specificity (0.96 [0.94-0.97], 0.95 [0.89-0.98]) values. According to the threshold effect analysis, the recommended cut-offs are 70% (sensitivity 0.89 [0.85-0.92], specificity 0.90 [0.87-0.93]), 4100/μL (sensitivity 0.90 [0.87-0.93], specificity 0.97 [0.93-0.98]), 13.5 mg/L (sensitivity 0.84 [0.78-0.89], specificity 0.83 [0.73-0.89]), and 30 mm/h (sensitivity 0.79 [0.74-0.83], specificity 0.78 [0.72-0.83]) for synovial PMN%, synovial WBC, serum CRP, and ESR, respectively, and tests seem to be more reliable among non-IA patients. The laboratory-based synovial α-defensin and synovial calprotectin are the two best independent preoperative diagnostic tests for PJI. A cut off of 70% for synovial PMN% and tighter cut-offs for synovial WBC and serum CRP could have a better diagnostic accuracy for non-IA patients with chronic PJI.

The combined measurement of synovial markers in the diagnosis of periprosthetic joint infection.

Currently there is no single test for periprosthetic joint infection (PJI) that demonstrates an acceptable level of sensitivity. The aim of this pilot study was to identify a combination of biomarkers that could exclude periprosthetic infection prior to revision surgery in hip and knee arthroplasty. This would help in equivocal cases of PJI, such as those with low-virulence organisms, chronic low-grade infection or 'aseptic' loosening. Current research has focused on measuring the levels of biomarkers in the patient's synovial fluid, and these can be combined to improve accuracy. We selected synovial white cell count (SF-WCC) and C-reactive protein (SF-CRP), as they demonstrated an acceptable level of sensitivity and specificity which could be measured using existing equipment. One hundred and sixty-one synovial fluid samples from 134 patients were collected and analysed prospectively using calculated cut-off values of 10mg/l for SF-CRP and 3,000×106/l for SF-WCC. Samples were deemed positive for infection when either of the SF-CRP or SF-WCC values were above the cut-off. The combined test demonstrated a sensitivity greater than 98.5% and specificity above 80% in all samples analysed or looked at separately for total hip replacement and total knee replacement infections. All ten aspirates taken from chronically infected joints tested positive. The combination of SF-CRP and SF-WCC measurement has been shown to have high sensitivity of over 99% in detecting both acute and chronic PJI in both hip and knee arthroplasty. This ability of the test to exclude infection with a high degree of certainty will help in preoperative planning of PJIs.

Serum D-lactate, a novel serological biomarker, is promising for the diagnosis of periprosthetic joint infection

BackgroundAlthough many markers are used for diagnosis of periprosthetic joint infection (PJI), serological screening and diagnosis for PJI are still challenging. We evaluated the performance of serum D-lactate and compared it with ESR, coagulation-related biomarkers and synovial D-lactate for the diagnosis of PJI.MethodsConsecutive patients with preoperative blood and intraoperative joint aspiration of a prosthetic hip or knee joint before revision arthroplasty were prospectively included. The diagnosis of PJI was based on the criteria of the Musculoskeletal Infection Society, and the diagnostic values of markers were estimated based on receiver operating characteristic (ROC) curves by maximizing sensitivity and specificity using optimal cutoff values.ResultsOf 52 patients, 26 (50%) were diagnosed with PJI, and 26 (50%) were diagnosed with aseptic failure. ROC curves showed that serum D-lactate, fibrinogen (FIB) and ESR had equal areas under the curve (AUCs) of 0.80, followed by D-dimer and fibrin degradation product, which had AUCs of 0.67 and 0.69, respectively. Serum D-lactate had the highest sensitivity of 88.46% at the optimal threshold of 1.14 mmol/L, followed by FIB and ESR, with sensitivities of 80.77% and 73.08%, respectively, while there were no significant differences in specificity (73.08%, 73.08% and 76.92%, respectively).ConclusionSerum D-lactate showed similar performance to FIB and ESR for diagnosis of PJI. The advantages of serum D-lactate are pathogen-specific, highly sensitive, minimally invasive and rapidly available making serum D-lactate useful as a point-of-care screening test for PJI.

Thromboelastography parameters in diagnosing periprosthetic joint infection and predicting reimplantation timing

BackgroundCoagulation-related biomarkers are drawing new attention in the diagnosis of periprosthetic joint infection (PJI). The thromboelastography (TEG) assay provides a comprehensive assessment of blood coagulation; therefore, it could be a promising test for PJI. This study aims to assess the value of TEG in diagnosing PJI and to determine the clinical significance of TEG in analysing reimplantation timing for second-stage revision.MethodsFrom October 2017 to September 2020, 62 patients who underwent revision arthroplasty were prospectively included. PJI was defined by the 2011 Musculoskeletal Infection Society criteria, in which 23 patients were diagnosed with PJI (Group A), and the remaining 39 patients were included as having aseptic loosening (Group B). In group A, 17 patients completed a two-stage revision in our centre. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), D-dimer, and TEG parameters (clotting time, α-angle, MA [maximum amplitude], amplitude at 30 min, and thrombodynamic potential index) were measured preoperatively in all included patients. In addition, receiver operating characteristic curves were used to evaluate the diagnostic value of these biomarkers.ResultsESR (area under curve [AUC], 0.953; sensitivity, 81.82; specificity, 94.87) performed best for PJI diagnosis, followed by MA (AUC, 0.895; sensitivity, 82.61; specificity, 97.44) and CRP (AUC, 0.893; sensitivity, 82.61; specificity, 94.74). When these biomarkers were combined in pairs, the diagnostic value improved compared with any individual biomarker. The overall success rate of the two-stage revision was 100%. Furthermore, ESR and MA were valuable in determining the time of reimplantation, and their values all decreased below the cut-off values before reimplantation.ConclusionTEG could be a promising test in assisting PJI diagnosis, and a useful tool in judging the proper timing of reimplantation.

Synovial fluid α defensin has comparable accuracy to synovial fluid white blood cell count and polymorphonuclear percentage for periprosthetic joint infection diagnosis.

The aim of this study was to determine the diagnostic accuracy of α defensin (AD) lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) tests for periprosthetic joint infection (PJI) in comparison to conventional synovial white blood cell (WBC) count and polymorphonuclear neutrophil percentage (PMN%) analysis. Patients undergoing joint aspiration for evaluation of pain after total knee arthroplasty (TKA) or total hip arthroplasty (THA) were considered for inclusion. Synovial fluids from 99 patients (25 THA and 74 TKA) were analyzed by WBC count and PMN% analysis, AD LFA, and AD ELISA. WBC and PMN% cutoffs of ≥ 1,700 cells/mm3 and ≥ 65% for TKA and ≥ 3,000 cells/mm3 and ≥ 80% for THA were used, respectively. A panel of three physicians, all with expertise in orthopaedic infections and who were blinded to the results of AD tests, independently reviewed patient data to diagnose subjects as with or without PJI. Consensus PJI classification was used as the reference standard to evaluate test performances. Results were compared using McNemar's test and area under the receiver operating characteristic curve (AUC) analysis. Expert consensus classified 18 arthroplasies as having failed due to PJI and 81 due to aseptic failure. Using these classifications, the calculated sensitivity and specificity of AD LFA was 83.3% (95% confidence interval (CI) 58.6 to 96.4) and 93.8% (95% CI 86.2 to 98.0), respectively. Sensitivity and specificity of AD ELISA was 83.3% (95% CI 58.6 to 96.4) and 96.3% (95% CI 89.6 to 99.2), respectively. There was no statistically significant difference between sensitivity (p = 1.000) or specificity (p = 0.157) of the two AD assays. AUC for AD LFA was 0.891. In comparison, AUC for synovial WBC count, PMN%, and the combination of the two values was 0.821 (sensitivity p = 1.000, specificity p < 0.001), 0.886 (sensitivity p = 0.317, specificity p = 0.011), and 0.926 (sensitivity p = 0.317, specificity p = 0.317), respectively. The diagnostic accuracy of synovial AD for PJI diagnosis is comparable and not statistically superior to that of synovial WBC count plus PMN% combined. Cite this article: Bone Joint J2021;103-B(6):1119-1126.

The Utility of MRI With Multiacquisition Variable-Resonance Image Combination (MAVRIC) in Diagnosing Deep Total Hip Arthroplasty Infection.

Background: The 2010 American Academy of Orthopaedic Surgeons Clinical Practice Guidelines report insufficient evidence to address the diagnostic efficacy of magnetic resonance imaging (MRI) for periprosthetic joint infection (PJI). Questions/Purposes: The purpose of this study was to determine the utility of MRI with multiacquisition variable-resonance image combination (MAVRIC) metal artifact suppression techniques in diagnosing PJI in the setting of total hip arthroplasty (THA). Methods: Multiacquisition variable-resonance image combination MRIs obtained of THAs between November 2012 and November 2016 were queried. Radiology reports were classified as positive (suspicious for infection), negative (no features of infection), or inconclusive (infection cannot be excluded or correlation with aspiration suggested if clinically concerned). Chart review identified cases of deep PJI according to the modified Musculoskeletal Infection Society criteria. Results: Of 2156 MRIs of THAs included, MRI was concerning for infection in 1.8% (n = 39), inconclusive in 1.2% (n = 26), and negative in 97.0% (n = 2091). Deep PJI was identified in 53 (2.5%) patients, 30 of whom (56.6%) had conclusively positive finding on MRI (false-negative rate: 43.4%, sensitivity: 56.6%). Of 2103 aseptic THAs, only 9 (0.4%) MRIs were read as suspicious for infection (false-positive rate: 0.4%; specificity: 99.6%). Conclusion: Magnetic resonance imaging with MAVRIC is a highly specific test for PJI with a low false-positive rate. This indicates that when clinicians are provided with an MRI that unexpectedly suggests infection, a formal evaluation for infection is indicated. In patients with otherwise equivocal diagnostic findings, MRI may help confirm, but not refute, a diagnosis of PJI. Prospective study with more experienced image reviewers may further support the use of MRI in PJI.

Current Guideline for Diagnosis of Periprosthetic Joint Infection: A Review Article.

The nature of implant-related infections is complex. Currently, there is no definitive test for periprosthetic joint infection (PJI) and diagnosis remains challenging despite recent developments. Failure to diagnose and investigate pathologies of the hip appropriately results in delayed management and prolonged patient morbidity. A systematic approach to establishing clear diagnostic criteria for PJI is needed to improve our ability to avoid devastating outcomes associated with these infections. In the current review, we describe an algorithmic approach to the diagnosis of PJI and current controversies surrounding novel diagnostic methods.

Synovial Fluid d-Lactate—A Novel Pathogen-Specific Biomarker for the Diagnosis of Periprosthetic Joint Infection

BackgroundSynovial fluid d-lactate may be useful for diagnosing periprosthetic joint infection (PJI) as this biomarker is exclusively produced by bacteria. We evaluated the performance of synovial fluid d-lactate using 2 definition criteria and determined its optimal cutoff value for diagnosing PJI. MethodsConsecutive patients undergoing joint aspiration before prosthesis revision were prospectively included. Synovial fluid was collected for culture, leukocyte count, and d-lactate concentration (by spectrophotometry). Youden's J statistic was used for determining optimal d-lactate cutoff value on the receiver operating characteristic curve by maximizing sensitivity and specificity. ResultsA total of 224 patients were included. Using Musculoskeletal Infection Society criteria, 71 patients (32%) were diagnosed with PJI and 153 (68%) with aseptic failure (AF), whereas using institutional criteria, 92 patients (41%) were diagnosed with PJI and 132 (59%) with AF. The optimal cutoff of synovial fluid d-lactate to differentiate PJI from AF was 1.3 mmol/L, independent of the used definition criteria. Synovial fluid d-lactate had a sensitivity of 94.3% (95% confidence interval [95% CI], 86.2-98.4) and specificity of 78.4% (95% CI, 66.8-81.2) using Musculoskeletal Infection Society criteria, whereas its sensitivity was 92.4% (95% CI, 84.9-96.9) and specificity 88.6% (95% CI, 81.9-93.5) using institutional criteria. The concentration of d-lactate was higher in infections caused by Staphylococcus aureus (P < .001) and streptococci (P = .016) than by coagulase-negative staphylococci or in culture-negative PJI. ConclusionThe synovial fluid d-lactate showed high sensitivity (>90%) for diagnosis of PJI using both definition criteria and correlated with the pathogen virulence. The high sensitivity makes this biomarker useful as a point-of-care screening test for PJI. Level of EvidenceDiagnostic level I.

New Methods in the Diagnosis of Prosthetic Joint Infection

A timely and accurate diagnosis of periprosthetic joint infection (PJI) is crucial to plan adequate treatment. Purpose of the study. To evaluate the performance of new diagnostic tests for the diagnosis of PJI. Material and Methods. The performance of novel biomarkers in synovial fluid (i.e. D-lactate and alfa-defensin), molecular test (i.e. PCR of synovial fluid and sonication fluid), new methods to dislodge biofilm from implant surface (i.e. MicroDTTect) and sonication of explanted prosthesis were investigated in patients with PJI and aseptic loosening of the prosthesis. Results. D-lactate showed better sensitivity for the diagnosis of PJI compared to leukocyte count (86% and 80%, respectively). The optimal D-lactate cut-off value was calculated at 1.26 mmol/l. The ADLF test showed sensitivity of 84%, 67% and to 54% depending on classification criteria used for the diagnosis of PJI (Musculoskeletal Infection Society (MSIS), The Infectious Diseases Society of America (IDSA) and proposed European Bone and Joint Infection Society (EBJIS) criteria, respectively). Using the proposed EBJIS definition criteria, the sensitivity of the leukocyte count was significantly higher than that of the ADLF test (86% compared with 54%; p0,001), particularly in chronic PJI (81% compared with 44%, respectively; p0,001). The sensitivity of synovial fluid PCR was 60% and herewith comparable with synovial fluid culture (52%, p = 0,239). The sensitivity and specificity of sonication fluid culture were 58% and 100%, which was comparable to sonication fluid PCR 51% and 94%, respectively. DTT-based method showed low sensitivity for diagnosis of PJI (40%) compared to sonication (80%, p0,01). Conclusion. Synovial fluid D-lactate demonstrated good analytical performance and diagnostic value for the diagnosis of PJI. In particular, the high sensitivity for diagnosing infection and rapid availability of the test result make synovial fluid D-lactate suitable as screening test, whereas ADLF had limited sensitivity (54%) but high specificity (95%) and it should therefore not be used for screening, but rather as a confirmatory test for PJI. Multiplex PCR of synovial fluid and sonication fluid has similar sensitivity and specificity compared to synovial fluid culture, having the advantage of rapid availability of results (within 5 hours) and fully automated process. With further improvement of its performance and inclusion of additional primers, multiplex PCR may complement conventional cultures, especially for rapid and accurate diagnosis of low-grade PJI. Culture of samples obtained by sonication of prostheses showed better sensitivity for the microbiologic diagnosis of prosthetic hip and knee infection compared to chemical based dislodgement such as MicroDTTect.

The Leukocyte Esterase Test for Periprosthetic Joint Infection Is Not Affected by Prior Antibiotic Administration.

It has been demonstrated that administration of antibiotics prior to performing diagnostic testing for periprosthetic joint infection can interfere with the accuracy of the standard diagnostic tests. Therefore, the purpose of this study was to evaluate the effects of antibiotic administration prior to performing the synovial leukocyte esterase strip test for periprosthetic joint infection. We identified 121 patients who underwent revision hip or knee arthroplasty for a Musculoskeletal Infection Society (MSIS)-confirmed periprosthetic joint infection. All patients also had a leukocyte esterase strip test performed. Patients in one group (32%) took antibiotics prior to the diagnostic workup, whereas patients in another group (68%) did not receive antibiotics within 2 weeks of the diagnostic workup. The leukocyte esterase strip test, erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), synovial white blood-cell (WBC) count, and polymorphonuclear neutrophil (PMN) percentage were collected and were compared between the 2 groups. The median serum ESR (85 compared with 67 mm/hr for patients who did not and did receive antibiotics; p = 0.009), CRP (16.5 compared with 12.9 mg/L; p = 0.032), synovial WBC count (45,675 compared with 9,650 cells/µL; p < 0.0001), and PMN percentage (93% compared with 88%; p = 0.004) were all significantly lower for patients receiving antibiotics. Furthermore, the administration of antibiotics resulted in a significant decrease in the sensitivity of all tests, except leukocyte esterase: ESR (79.5% in the antibiotics cohort compared with 92.7% in the no-antibiotics cohort [relative risk (RR) for false-negative results, 2.8; p = 0.04]), CRP (64.2% compared with 81.8% [RR, 1.9; p = 0.03]), WBC count (69.3% compared with 93.4% [RR, 5.0; p = 0.001]), PMN percentage (74.4% compared with 91.5% [RR, 3.0; p = 0.01]), and leukocyte esterase (78% compared with 83% [RR, 1.6; p = 0.17]). The rate of negative cultures was higher in the antibiotics group at 30.7% compared with the no-antibiotics group at 12.1% (p = 0.015). This current study and previous studies have demonstrated that the administration of premature antibiotics can compromise the results of standard diagnostic tests for periprosthetic joint infection, causing significant increases in false-negative results. However, in this study, the leukocyte esterase strip test maintained its performance even in the setting of antibiotic administration. Antibiotic administration prior to diagnostic workups for periprosthetic joint infection stands to interfere with diagnosis. The leukocyte esterase strip test can be used as a reliable diagnostic marker for diagnosing periprosthetic joint infection even when prior antibiotics are administered. Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Diagnostic Accuracy of the Alpha-Defensin Test for Periprosthetic Joint Infection in Patients With Inflammatory Diseases

BackgroundThe alpha-defensin test has been reported to have high accuracy to diagnose periprosthetic joint infection (PJI). There are remaining concerns about the utility of the test in patients with inflammatory diseases. The purpose of this study is to determine sensitivity and specificity of laboratory-based alpha-defensin in diagnosing PJI in patients with systemic inflammatory disease in revision total hip/knee arthroplasty. MethodsA retrospective review was conducted of 1374 cases who underwent revision total hip/knee arthroplasty at a single healthcare system from 2014 to 2017. Cases with inflammatory diseases who received a 1-stage revision arthroplasty, the first stage of 2-stage revision arthroplasty, or irrigation and debridement with available preoperative alpha-defensin results were included. Patients who received a second-stage procedure, spacer exchange, who had insufficient Musculoskeletal Infection Society criteria, or with early postoperative PJI were excluded from this study. Cases were classified as infected or not according to Musculoskeletal Infection Society criteria. A total of 41 cases met the inclusion criteria. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of alpha-defensin to diagnose PJI were calculated. ResultsThe alpha-defensin test demonstrated a sensitivity of 93%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 96%, and an accuracy of 97% for diagnosing PJI. There was 1 patient with polymyositis who had a false-negative result. ConclusionAlpha-defensin had high accuracy for diagnosing PJI even in inflammatory diseases. The alpha-defensin test provides useful information with high accuracy in diagnosing PJI in patients with inflammatory diseases.

Routine Diagnostic Tests for Periprosthetic Joint Infection Demonstrate a High False-Negative Rate and Are Influenced by the Infecting Organism.

Current guidelines recommend serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as the first-line testing for evaluation of suspected periprosthetic joint infection, in addition to synovial white blood-cell (WBC) count and polymorphonuclear percentage. However, the sensitivity and other diagnostic measures of these tests using a standardized definition of periprosthetic joint infection and the influence of organisms on these inflammatory markers remain inadequately investigated. A retrospective review of an institutional database of 549 periprosthetic joint infection cases and 653 aseptic total joint arthroplasty revisions was performed. Periprosthetic joint infection was defined using major criteria from the International Consensus Meeting (ICM) on Periprosthetic Joint Infection. The mean inflammatory marker levels were compared among organisms with Student t tests and the proportions of elevated laboratory levels were compared among organisms with chi-square analyses. Receiver operating characteristic curve analyses were performed to calculate new cutoffs, sensitivities, and specificities for each organism and overall for serum CRP and ESR and synovial WBC and polymorphonuclear percentage. The sensitivity of these markers for diagnosing chronic periprosthetic joint infection was 0.85 for ESR, 0.88 for CRP, 0.83 for WBC count, and 0.78 for polymorphonuclear percentage. For ESR, antibiotic-resistant organisms had higher mean values (84.3 mm/hr) than culture-negative cases (57.4 mm/hr), coagulase-negative Staphylococcus (68.3 mm/hr), and Streptococcus species (66.1 mm/hr); Staphylococcus aureus (81.0 mm/hr) was higher than culture-negative cases (57.4 mm/hr). For CRP, culture-negative cases had lower mean values (41.0 mg/L) than gram-negative organisms (87.4 mg/L), antibiotic-resistant organisms (86.0 mg/L), S. aureus (112.2 mg/L), and Streptococcus species (114.6 mg/L); S. aureus (112.2 mg/L) was higher than coagulase-negative Staphylococcus (66.0 mg/L). For WBC count, culture-negative cases had lower mean values (27,984.5 cells/mL) than S. aureus (116,250.0 cells/mL) and Streptococcus species (77,933.7 cells/mL). For polymorphonuclear percentage, there were no significant differences in mean values among all organisms. It appears that serological markers, namely ESR and CRP, have a higher false-negative rate than previously reported. Synovial markers similarly exhibit high false-negative rates. Furthermore, the sensitivity of these tests appears to be related to organism type. Surgeons should be aware of the high rate of false-negatives associated with low-virulence organisms and culture-negative cases. Diagnostic Level I. See Instructions for Authors for a complete description of levels of evidence.

Clinical Evaluation of Synovial Alpha Defensin and Synovial C-Reactive Protein in the Diagnosis of Periprosthetic Joint Infection.

Diagnosing periprosthetic joint infection after total joint arthroplasty is often challenging. The alpha defensin test has been recently reported as a promising diagnostic test for periprosthetic joint infection. The goal of this study was to determine the diagnostic accuracy of alpha defensin testing. One hundred and eighty-three synovial alpha defensin and synovial fluid C-reactive protein (CRP) tests performed in 183 patients undergoing evaluation for periprosthetic joint infection were reviewed. Results were compared with the Musculoskeletal Infection Society (MSIS) criteria for periprosthetic joint infection. Alpha defensin tests were performed prior to surgical treatment for infection, and 37 of these patients who had these tests were diagnosed by MSIS criteria as having infections. Among this group, the alpha defensin test had a sensitivity of 81.1% (95% confidence interval [CI], 64.8% to 92.0%) and a specificity of 95.9% (95% CI, 91.3% to 98.5%). There were 6 false-positive results, 4 of which were associated with metallosis. There were 7 false negatives, all of which were associated with either draining sinuses (n = 3) or low-virulence organisms (n = 4). A combined analysis of alpha defensin and synovial fluid CRP tests was performed in which a positive result was represented by a positive alpha defensin test and a positive synovial fluid CRP test (n = 28). Among this group, the sensitivity was calculated to be 73.0% (95% CI, 55.9% to 86.2%) and the specificity was calculated to be 99.3% (95% CI, 96.2% to 99.9%). An additional combined analysis was performed where a positive result was represented by a positive alpha defensin test or positive synovial fluid CRP test (n = 64). Among this group, the sensitivity was calculated to be 91.9% (95% CI, 78.1% to 98.3%) and the specificity was calculated to be 79.5% (95% CI, 72.0% to 85.7%). Alpha defensin in combination with synovial fluid CRP demonstrates very high sensitivity for diagnosing periprosthetic joint infection, but may yield false-positive results in the presence of metallosis or false-negative results in the presence of low-virulence organisms. When both alpha defensin and synovial fluid CRP tests are positive, there is a very high specificity for diagnosing periprosthetic joint infection. Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Alpha Defensin Lateral Flow Test for Diagnosis of Periprosthetic Joint Infection: Not a Screening but a Confirmatory Test.

Determination of alpha defensin in synovial fluid has shown promising results for diagnosing periprosthetic joint infection (PJI). The purposes of our study were to assess the performance of alpha defensin lateral flow (ADLF) test for the diagnosis of acute and chronic PJI using 3 classification systems and to compare its performance with the synovial fluid leukocyte count. Patients in whom aspiration of a prosthetic hip or knee joint was performed before revision arthroplasty were prospectively included. In addition to standard diagnostic tests, the ADLF test was performed in synovial fluid. Patients were classified as having PJI or aseptic failure according to the definition criteria of the Musculoskeletal Infection Society (MSIS), the Infectious Diseases Society of America (IDSA), and the proposed criteria of the European Bone and Joint Infection Society (EBJIS). The performance of the ADLF test and the leukocyte count was compared using the McNemar chi-square test. Of 212 included patients, 151 (71%) had a knee prosthesis and 61 (29%) had a hip prosthesis. PJI was diagnosed in 45 patients (21%) using the MSIS criteria, in 55 patients (26%) using the IDSA criteria and in 79 patients (37%) using the proposed EBJIS criteria. The sensitivity of the ADLF test was 84% (95% confidence interval [CI], 71% to 94%) with the MSIS criteria, 67% (95% CI, 53% to 79%) with the IDSA criteria, and 54% (95% CI, 43% to 66%) with the proposed EBJIS criteria. The ADLF test showed high specificity using all classification criteria (96% to 99%) and represented the most specific preoperative test for PJI, especially in the early postoperative period (91%; 95% CI, 59% to 100%). Using the proposed EBJIS definition criteria, the sensitivity of the leukocyte count was significantly higher than that of the ADLF test (86% [95% CI, 76% to 93%] compared with 54% [95% CI, 43% to 66%]; p < 0.001), particularly in chronic PJI (81% compared with 44%, respectively; p < 0.001). The ADLF test was rapid and highly specific for diagnosing PJI (>95%). However, its sensitivity was limited (54% to 84%) and it should therefore not be used for screening, but rather as a confirmatory test for PJI. Diagnostic Level I. See Instructions for Authors for a complete description of levels of evidence.

The Leukocyte Esterase Test Strip Is a Poor Rule-Out Test for Periprosthetic Joint Infection

BackgroundThe urinary leukocyte esterase (LE) test strip has been suggested as a good screening test for periprosthetic joint infection (PJI). The purpose of this study is to compare the diagnostic profile of LE assays from different manufacturers and determine whether the LE test strip is a good rule-out test. MethodsSynovial fluid samples (N = 344), sent to 1 laboratory for PJI testing, were used in this prospective study. Four different tests for synovial fluid LE were simultaneously evaluated for their performance in detecting white blood cell (WBC) positive samples (>3000 cells/µL). ResultsBoth neutrophil elastase immunoassays demonstrated greater sensitivity than urinary LE test strips (92.0% and 90.8% vs 72.4% and 80.3%; all P < 0.011). Fifty-three percent of false-negative urinary LE test strip results clearly missed the presence of elevated levels of synovial fluid LE. Invalid urinary LE test strip results were 4-fold more likely among WBC (+) compared with WBC (−) samples (27.0% vs 6.8%; P < 0.0001). The combined failure to detect an elevated WBC count, because of either false-negative or invalid results, was 47.1% and 41.4% for the Roche and Siemens test strips, respectively. ConclusionsThis study agrees with the existing literature demonstrating that the LE test strips are among the lowest sensitivity tests for PJI. The urinary LE tests strips should not be used to rule-out PJI, as they often fail to detect abundant levels of LE in synovial fluid. Instead, it is more appropriate to use the (++) LE test strip result as a secondary confirmatory rule-in test for PJI because of its high specificity.

The Alpha-Defensin Test for Diagnosing Periprosthetic Joint Infection in the Setting of an Adverse Local Tissue Reaction Secondary to a Failed Metal-on-Metal Bearing or Corrosion at the Head-Neck Junction

BackgroundIn patients with adverse local tissue reaction (ALTR) secondary to a failed metal-on-metal (MoM) bearing or corrosion at the head-neck junction in a metal-on-polyethylene bearing, ruling in or out periprosthetic joint infection (PJI) can be challenging. Alpha-defensin has emerged as an accurate test for PJI. The purpose of this multicenter, retrospective study was to evaluate the accuracy of the alpha-defensin synovial fluid test in detecting PJI in patients with ALTR. MethodsWe reviewed medical records of 26 patients from 3 centers with ALTR that had an alpha-defensin test performed. Patients were assessed for PJI using the Musculoskeletal Infection Society criteria. Thirteen of these subjects had MoM total hip arthroplasty, 9 had ALTR secondary to head-neck corrosion, and 4 had MoM hip resurfacing. ResultsOnly 1 of the 26 patients met Musculoskeletal Infection Society criteria for infection. However, 9 hips were alpha-defensin positive, including 1 true positive and 8 that were falsely positive (31%). All 8 of the false positives were also Synovasure positive, although 5 of 8 had an accompanying warning stating the results may be falsely positive due to a low synovial C-reactive protein value. ConclusionSimilar to synovial fluid white blood cell count, alpha-defensin testing is prone to false-positive results in the setting of ALTR. Therefore, we recommend an aggressive approach to ruling out PJI including routine aspiration of all hips with ALTR before revision surgery to integrate the synovial fluid blood cell count, differential, cultures and adjunctive tests like alpha-defensin to allow for accurate diagnosis preoperatively.