Diagnosing Periprosthetic Joint Infection in Inflammatory Arthritis: Assumption Is the Enemy of True Understanding

Background

Despite concern over the interpretation of serum and synovial fluid tests to screen and diagnose periprosthetic joint infection (PJI) in patients with inflammatory arthritis, only a single study has investigated this area. We aimed to assess accuracy of clinical and laboratory markers for PJI diagnosis in the context of underlying inflammatory arthritis.

Mortality During Total Knee Periprosthetic Joint Infection

Background

Periprosthetic joint infections (PJIs) are fraught with multiple complications including poor patient-reported outcomes, disability, reinfection, disarticulation, and even death. We sought to perform a systematic review asking the question: (1) What is the mortality rate of a PJI of the knee undergoing 2-stage revision for infection? (2) Has this rate improved over time? (3) How does this compare to a normal cohort of individuals?

Plasma Fibrin Degradation Product and D-Dimer Are of Limited Value for Diagnosing Periprosthetic Joint Infection

BackgroundAlthough the Musculoskeletal Infection Society introduced the use of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as inflammatory markers for diagnosing periprosthetic joint infection (PJI), no single blood marker reliably detects infection before revision arthroplasty. We therefore posed 2 questions: (1) Are fibrin degradation product (FDP) and D-dimer of value for diagnosing PJI before revision arthroplasty? (2) What are their sensitivity and specificity for that purpose?MethodsTo answer these questions, we retrospectively enrolled 318 patients (129 with PJI [group A], 189 with aseptic mechanical failure [group B]) who underwent revision arthroplasty during 2013-2018. Receiver operating characteristic curves were used to determine maximum sensitivity and specificity of the 2 markers. Inflammatory and fibrinolytic markers were evaluated based on (1) the Tsukayama-type infection present and (2) the 3 most common PJI-related pathogens.ResultsFDP and D-dimer levels were higher in group A than in group B: 4.97 ± 2.83 vs 4.14 ± 2.67 mg/L and 2.14 ± 2.01 vs 1.51 ± 1.37 mg/L fibrinogen equivalent units (FEU), respectively (both P < .05). Based on the Youden index, 2.95 mg/L and 1.02 mg/L FEU are the optimal FDP and D-dimer predictive cutoffs, respectively, for diagnosing PJI. Sensitivity and specificity, respectively, were 65.12% and 60.33% (FDP) and 68.29% and 50.70% (D-dimer). ESR, CRP, and interleukin-6 values were diagnostically superior to those of FDP and D-dimer.ConclusionThe value of plasma FDP and D-dimer for diagnosing PJI is limited compared with traditional inflammatory markers (ESR, CRP, interleukin-6) before revision arthroplasty.     

External Validation Demonstrates Limited Clinical Utility of a Preoperative Prognostic Calculator for Periprosthetic Joint Infection

BackgroundPreoperative calculation of treatment failure risk in patients undergoing surgery for periprosthetic joint infection (PJI) is imperative to allow for medical optimization and targeted prevention. A preoperative prognostic model for PJI treatment failure was previously developed, and this study sought to externally validate the model.MethodsA retrospective review was performed of 380 PJIs treated at two institutions. The model was used to calculate the risk of treatment failure, and receiver operating characteristic curves were generated to calculate the area under the curve (AUC) for each institution.ResultsWhen applying this model to institution 1, an AUC of 0.795 (95% confidence interval [CI]: 0.693-0.897) was found, whereas institution 2 had an AUC of 0.592 (95% CI: 0.502-0.683). Comparing all institutions in which the model had been applied to, we found institution 2 represented a significantly sicker population and different infection profile.ConclusionIn this cohort study, we externally validated the prior published model for institution 1. However, institution 2 had a decreased AUC using the prior model and represented a sicker and less homogenous cohort compared with institution 1. When matching for chronicity of the infection, the AUC of the model was not affected. This study highlights the impact of comorbidities and their distributions on PJI prognosis and brings to question the clinical utility of the algorithm which requires further external validation.     

The Utility of Frozen Section Histology in Diagnosing Periprosthetic Joint Infection in Revision Total Joint Arthroplasty

BackgroundSurgeons utilize a combination of preoperative tests and intraoperative findings to diagnose periprosthetic joint infection (PJI); however, there is currently no reliable diagnostic marker that can be used in isolation. The purpose of our study is to evaluate the utility of frozen section histology in diagnosis of PJI.MethodsRetrospective analysis of 614 patients undergoing revision total joint arthroplasty with frozen section histology from a single institution was performed. Discriminatory value of frozen section histology was assessed using univariate analysis and evaluation of area under the curve (AUC) of a receiver operating characteristic curve comparing frozen section histology results to the 2018 International Consensus Meeting (ICM) PJI criteria modified to exclude the histology component.ResultsThe sensitivity of the frozen section histology was 53.6% and the specificity was 95.2%. There was 99.2% concordance between the permanent section and frozen section results. The receiver operating characteristic curve for frozen section yielded an AUC of 0.744 (95% confidence interval 0.627-0.860) and the modified ICM score yielded an AUC of 0.912 (95% confidence interval 0.836-0.988) when compared to the full score. The addition of frozen section histology changed the decision to infected in 20% of “inconclusive” cases but less than 1% of total cases.ConclusionIn comparison to the modified ICM criteria, intraoperative frozen section histology has poor sensitivity, strong specificity, and acceptable overall discrimination for diagnosing PJI. This test appears to be of particular value for patients deemed “inconclusive” for infection using the remaining ICM criteria.     

Plasma Fibrinogen and Platelet Count Are Referable Tools for Diagnosing Periprosthetic Joint Infection: A Single-Center Retrospective Cohort Study

BackgroundAlthough the MusculoSkeletal Infection Society has suggested a series of markers to diagnose periprosthetic joint infection (PJI), no single marker can accurately identify infection before revision hip or knee arthroplasty, and exploring promising markers to easily and reliably diagnose PJI is ongoing. The aim of this study was to evaluate the diagnostic value of plasma fibrinogen and platelet count for diagnosing PJI.MethodsWe retrospectively included 439 patients who underwent revision arthroplasty from January 2008 to December 2018; 79 patients with coagulation-related comorbidities were evaluated separately. The remaining 360 patients constituted 153 PJI and 207 non-PJI patients. Receiver operating characteristic curves were used to evaluate the maximum sensitivity and specificity of the tested markers.ResultsThe receiver operating characteristic curves showed that the areas under the curve for plasma fibrinogen, platelet count, and serum C-reactive protein and erythrocyte sedimentation rate were 0.834, 0.746, 0.887, and 0.842, respectively. Based on Youden's index, the optimal predictive cutoffs for fibrinogen and platelet count were 3.57 g/L and 221 × 10⁹/L, respectively. The sensitivity and specificity, respectively, were 68.6% and 86.0% (fibrinogen) and 57.5% and 83.1% (platelet count) for diagnosing PJI. The sensitivity and specificity, respectively, were 76.7% and 72.2% (fibrinogen) and 48.8% and 63.9% (platelet count) for diagnosing PJI in patients with coagulation-related comorbidities.ConclusionPlasma fibrinogen performed well for diagnosing PJI before revision arthroplasty, and its value neared that of traditional inflammatory markers. Although the diagnostic value of the platelet count was inferior to traditional markers, its diagnostic value was fair for diagnosing PJI. Fibrinogen also may be useful for diagnosing PJI in patients with coagulation-related comorbidities.     

Synovial Fluid Calprotectin for the Preoperative Diagnosis of Chronic Periprosthetic Joint Infection

BackgroundThe diagnosis of periprosthetic joint infection (PJI) represents a challenge in clinical practice and the analysis of synovial fluid is a useful diagnostic tool. Calprotectin is an inflammatory biomarker widely used in the evaluation of chronic inflammatory diseases; however, little is known about its role in PJI. The purpose of this study is to determine the reliability of synovial calprotectin in the diagnosis of PJI.MethodsSeventy-six patients with painful knee arthroplasty were included in this prospective observational study. Synovial fluid was analyzed for cell count, percentage of polymorphonuclear neutrophils, microbiological culture, leukocyte esterase strip test, alpha-defensin rapid test, and calprotectin immunoassay dosage. The 2018 Consensus Statements criteria for PJI were used as standard reference to define the presence of infection. Sensitivity, specificity, positive and negative likelihood ratio, and receiver-operation characteristic curve were calculated for calprotectin immunoassay test.ResultsBy 2018 Consensus Statements criteria for PJI, 28 patients were considered infected, 44 patients were considered not infected, and 4 patients were classified as inconclusive. The calprotectin synovial fluid test resulted in 2 false-positive results and no false-negative results. The calprotectin synovial fluid test demonstrated a sensitivity of 100% (95% confidence interval [CI] 99.96-100) and specificity of 95% (95% CI 89.4-100) for the diagnosis of PJI. The positive likelihood ratio was 22 (95% CI 5.680-85.209) and the negative likelihood ratio was 0 (95% CI 0-0.292). The area under the receiver-operation characteristic curve was 0.996 (95% CI 94.3-100).ConclusionThe present study suggests that synovial calprotectin immunoassay test has a high sensitivity and specificity in the diagnosis of knee PJI. Moreover, it is easily applied, quick and valuable in clinical practice.     

Concomitant Hip and Knee Periprosthetic Joint Infection in Periprosthetic Fracture: Diagnostic Utility of Serum and Synovial Fluid Markers

BackgroundDiagnosing periprosthetic joint infection (PJI) in patients with a periprosthetic fracture can be challenging due to concerns regarding the reliability of commonly used serum and synovial fluid markers. This study aimed at determining the diagnostic performance of serum and synovial fluid markers for diagnosing PJI in patients with a periprosthetic fracture of a total joint arthroplasty.MethodsA total of 144 consecutive patients were included: (1) 41 patients with concomitant PJI and periprosthetic fracture and (2) 103 patients with periprosthetic fracture alone. Serum markers erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and synovial markers white blood cell (WBC) count and polymorphonuclear percentage were assessed.ResultsESR demonstrated 87% sensitivity and 48% specificity at the Musculoskeletal Infection Society threshold, area under the curve (AUC) of 0.74, and optimal threshold of 45.5 mm/h (76% sensitivity, 68% specificity). CRP showed 94% sensitivity and 40% specificity, AUC of 0.68 with optimal threshold of 16.7 mg/L (84% sensitivity, 51% specificity). Synovial WBC count demonstrated 87% sensitivity and 78% specificity, AUC of 0.90 with optimal threshold of 4552 cells/μL (86% sensitivity, 85% specificity). Polymorphonuclear percentage showed 79% sensitivity and 63% specificity, AUC of 0.70 with optimal threshold of 79.5% (74% sensitivity, 63% specificity). The AUC of all combined markers was 0.90 with 84% sensitivity and 79% specificity.ConclusionThe diagnostic utility of the serum and synovial markers for diagnosing PJI was lower in the setting of concomitant periprosthetic fracture compared to PJI alone. Using the Musculoskeletal Infection Society thresholds, ESR, CRP, and WBC count showed high sensitivity, yet low specificity, thus higher thresholds and utilizing all serum and synovial markers in combination should be considered.     

Synovial Fluid Alpha-Defensin Is an Adjunctive Tool in the Equivocal Diagnosis of Periprosthetic Joint Infection

Background

Synovial fluid alpha-defensin has shown to be a reliable diagnostic test for the diagnosis of periprosthetic joint infection (PJI), but its use in equivocal cases has yet to be established. The purpose of this study was to determine the reliability of alpha-defensin testing in patients, where the diagnosis of PJI was unclear.

Periprosthetic Joint Infection in Patients with Inflammatory Joint Disease: a Review of Risk Factors and Current Approaches to Diagnosis and Management

Background

Prevention, early identification, and effective management of periprosthetic joint infection (PJI) in patients with inflammatory joint disease (IJD) present unique challenges for physicians. Discontinuing disease-modifying anti-rheumatoid drugs (DMARDs) perioperatively may reduce immunosuppression and infection risk at the expense of increasing disease flares. Interpreting traditional diagnostic markers of PJI can be difficult due to disease-related inflammation.

Purposes

This review is designed to answer how to (1) manage immunosuppressive/DMARD therapy perioperatively, (2) diagnose PJI in patients with IJD, and (3) treat PJI in this population.

Methods

The PubMed database was searched for relevant articles with subsequent review by independent authors.

Results

While there is evidence to support the use of methotrexate perioperatively in RA patients, it remains unclear whether using anti-tumor necrosis factor medications perioperatively increases the risk of surgical site infections. Serum erythrocyte sedimentation rate and C-reactive protein can be useful for diagnosis of PJI in this population, but only as part of comprehensive workup that ultimately relies upon sampling of joint fluid. Management of PJI depends on several clinical factors including duration of infection and the likelihood of biofilm presence, the infecting organism, sensitivity to antibiotic therapy, and host immune status. The evidence suggests that two-stage revision or resection arthroplasty is more likely to eradicate infection, particularly when MRSA is the pathogen.

Conclusion

Immunosuppression and baseline inflammatory changes in the IJD population can complicate the prevention, diagnosis, and treatment of PJI. Understanding the increase in risk associated with IJD and its treatment is essential for proper management when patients undergo lower extremity arthroplasty.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-013-9338-8) contains supplementary material, which is available to authorized users.     

In-Hospital Mortality in Patients With Periprosthetic Joint Infection

Background

While periprosthetic joint infection (PJI) has a huge impact on patient function and health, only a few studies have investigated its impact on mortality. The purpose of this large-scale study was to (1) determine the rate and trends of in-hospital mortality for PJI and (2) compare the in-hospital mortality rate of patients with PJI and those undergoing revision arthroplasty for aseptic failure and patients undergoing other nonorthopedic major surgical procedures.

The Utility of Serum d-Dimer for the Diagnosis of Periprosthetic Joint Infection in Revision Total Hip and Knee Arthroplasty

BackgroundThere is scarce and contradicting evidence supporting the use of serum d-dimer for the diagnosis of periprosthetic joint infection in revision total hip (THA) and knee (TKA) arthroplasty. Therefore, the purpose of this study is to test the accuracy of serum d-dimer against the 2013 International Consensus Meeting (ICM) criteria.MethodsA retrospective review was performed on a consecutive series of 172 revision THA/TKA surgeries performed by 3 fellowship-trained surgeons at a single institution (August 2017 to May 2019) and that had d-dimer performed during their preoperative workup. Of this cohort, 111 (42 THAs/69 TKAs) cases had complete 2013 ICM criteria tests and were included in the final analysis. Septic and aseptic revisions were categorized per 2013 ICM criteria (“gold standard”) and compared against serum d-dimer using an established threshold (850 ng/mL). Sensitivity, specificity, likelihood ratios, and positive/negative predictive values were determined. Independent t-tests, Fisher’s exact tests, chi-squared tests, and receiver operating characteristic curve analysis were performed.ResultsThere was no statistically significant difference in baseline demographics between septic and aseptic cases per 2013 ICM criteria. When compared to ICM criteria, d-dimer demonstrated high sensitivity (95.9%) and negative predictive value (90.9%) but low specificity (32.3%), positive predictive value (52.8%), and overall, poor accuracy (61%) to diagnose periprosthetic joint infection. Positive likelihood ratio was 1.42 while negative likelihood ratio was 0.13. The area under the curve (AUC) was 0.742.ConclusionSerum d-dimer has poor accuracy to discriminate between septic and aseptic cases using a described threshold in the setting of revision THA and TKA.     

Management of Periprosthetic Joint Infection: The More We Learn,the Less We Know

BackgroundDespite the tremendous and long-standing success of total hip arthroplasty and total knee arthroplasty as treatments for end-stage arthritis, periprosthetic joint infection (PJI) remains a rare but feared complication of these procedures.MethodsThis review highlights some of the difficulties inherent to studying PJI. These include the difficulty in powering studies to capture this relatively uncommon complication, as well as the heterogeneity in clinical presentation and manifestations associated with the diagnosis and treatment of PJI.ConclusionWe suggest an algorithm for moving forward with new research in an attempt to answer the challenging questions facing the arthroplasty community regarding PJI.     

Hospital Costs for Unsuccessful Two-Stage Revisions for Periprosthetic Joint Infection

BackgroundAlthough 2-stage exchange arthroplasty is the preferred surgical treatment for periprosthetic joint infection (PJI) in the United States, little is known about the risk of complications between stages, mortality, and the economic burden of unsuccessful 2-stage procedures.MethodsThe 2015-2019 Medicare 100% inpatient sample was used to identify 2-stage PJI revisions in total hip and knee arthroplasty patients using procedural codes. We used the Fine and Gray sub-distribution adaptation of the conventional Kaplan-Meier method to estimate the probability of completing the second stage of the 2-stage PJI infection treatment, accounting for death as a competing risk. Hospital costs were estimated from the hospital charges using “cost-to-charge” ratios from Centers for Medicare and Medicaid Services.ResultsA total of 5094 total hip arthroplasty and 13,062 total knee arthroplasty patients had an index revision for PJI during the study period. In the first 12 months following the first-stage explantation, the likelihood of completing a second-stage PJI revision was 43.1% (95% confidence interval [CI] 41.7-44.5) for hips and 47.9% (95% CI 47.0-48.8) for knees. Following explantation, 1-year patient survival rates for hip and knee patients were 87.4% (95% CI 85.8-88.9) and 91.4% (95% CI 90.6-92.2), respectively. The median additional cost for hospitalizations between stages was $23,582 and $20,965 per patient for hips and knees, respectively. Hospital volume, Northeast or Midwest region, and younger age were associated with reduced PJI costs (P < .05).ConclusionAlthough viewed as the most preferred, the 2-stage revision strategy for PJI had less than a 50% chance of successful completion within the first year, and was associated with high mortality rates and substantial costs for treatment failure.     

The 2018 International Consensus Meeting Minor Criteria for Chronic Hip and Knee Periprosthetic Joint Infection: Validation From a Single Center

BackgroundRecently, a revised definition of the minor criteria scoring system for diagnosing periprosthetic joint infection (PJI) was developed by the second International Consensus Meeting on musculoskeletal infection. The new system combines preoperative and intraoperative findings, reportedly achieving high sensitivity and specificity. We aimed to validate the modified scoring system at a high-volume center.MethodsWe retrospectively reviewed patients who underwent a revision total hip or knee arthroplasty at our institution from May 2015 to August 2018. Serum C-reactive protein, synovial white blood cell count and polymorphonuclear percentage, leukocyte esterase test, alpha-defensin, microbiological and histologic results, and documented existence of sinus tract and intraoperative purulence were available for all patients. Cases with at least 1 major criterion were considered as infected. Using the new minor criteria, a score of ≥6 reflects PJI, while a score <3 can be considered as noninfected. Sensitivity, specificity, mean accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) were analyzed.ResultsA total of 345 cases were included. A cutoff score of ≥6 points had the following diagnostic performance: area under the curve (AUC) = 0.90; ACC = 0.88; sensitivity = 0.96; specificity = 0.84; PPV = 0.70; NPV = 0.98. Diagnostic performance was better for the hip (AUC = 0.92; ACC = 0.90; sensitivity = 0.96; specificity = 0.86; PPV = 0.81; NPV = 0.98) than the knee (AUC = 0.89; ACC = 0.85; sensitivity = 0.95; specificity = 0.83; PPV = 0.59; NPV = 0.98).ConclusionThe modified scoring system proposed by the 2018 International Consensus Meeting in diagnosing PJI showed high sensitivity and a good performance, especially as rule-out diagnostic criteria. The cutoff level seems to be different between the hip and knee. Further validation studies considering the acknowledged limitations are recommended.     

Low-Dose Aspirin for Venous Thromboembolism Prophylaxis is Associated With Lower Rates of Periprosthetic Joint Infection After Total Joint Arthroplasty

BackgroundAspirin as a venous thromboembolism (VTE) prophylactic agent has been shown to have antistaphylococcal and antibiofilm roles. Optimal acetylsalicylic acid (ASA) dosage would facilitate antimicrobial effects while avoiding over-aggressive inhibition of platelet antimicrobial function. Our purpose was to determine the periprosthetic joint infection (PJI) rate after total joint arthroplasty in patients receiving low-dose ASA (81 mg twice a day), in comparison to high-dose ASA (325 mg twice a day).MethodsWe conducted a retrospective cohort study between 2008 and 2020. Eligible patients were older than 18 years, underwent primary total joint arthroplasty, both total knee arthroplasty and total hip arthroplasty, had a minimum 30-day follow-up, and received a full course ASA as VTE prophylaxis. Patients’ records were reviewed for PJI, according to Musculoskeletal Infection Society criteria. Patients were excluded if they underwent revision arthroplasty, had a history of coagulopathy, or had an ASA regimen that was not completed. In total 15,825 patients were identified, 8,761 patients received low-dose ASA and 7,064 received high-dose ASA.ResultsThe high-dose cohort had a higher PJI rate (0.35 versus 0.10%, P = .001). This relationship was maintained when comparing subgroups comprising total knee arthroplasty (0.32 versus 0.06%, P = .019) or total hip arthroplasty (0.38 versus 0.14%, P = .035) and accounting for potentially confounding demographic and surgical variables (odds ratio = 2.59, 95% CI = 1.15-6.40, P = .028).ConclusionComparing low-dose to high-dose ASA as a VTE prophylactic agent, low-dose ASA had a lower PJI rate. This may be attributable to a balance of anti-infective properties of ASA and antiplatelet effects.     

Longer Operative Time Results in a Higher Rate of Subsequent Periprosthetic Joint Infection in Patients Undergoing Primary Joint Arthroplasty

Background

Whether prolonged operative time is an independent risk factor for subsequent surgical site infection (SSI) and periprosthetic joint infection (PJI) following total joint arthroplasty (TJA) remains a clinically significant and underexplored issue. The aim of this study is to investigate the association between operative time and the risk of subsequent SSI and PJI in patients undergoing primary TJA.

A Novel Adjunct Indicator of Periprosthetic Joint Infection: Platelet Count and Mean Platelet Volume

BackgroundDiagnosing a periprosthetic joint infection (PJI) is difficult and often requires a combination of objective findings. The purpose of this study is to determine whether platelets, a known acute phase reactant, would be able to further aid in the diagnosis of PJI.MethodsA single-institution retrospective review study was performed on all revision total hip and knee arthroplasties done between 2000 and 2016 (n = 4939). PJI was defined by Musculoskeletal Infection Society criteria (n = 949). Platelet count and mean platelet volume were assessed from each patient’s preoperative complete blood count. These values were then assessed as a ratio via receiver operating characteristic (ROC) curve analysis.ResultsThe platelet count to mean platelet volume ratio for PJI patients was 33.45 compared to 25.68 for patients in the aseptic revision cohort (P < .001). ROC curve analysis demonstrates that a ratio of 31.70 has a sensitivity of 48.10 (95% confidence interval 44.9-51.4) and a specificity of 80.85 (95% confidence interval 79.6-82.1). This specificity was higher than that of both estimated sedimentation ratio (ESR) and C-reactive protein (CRP) for the same cohorts using optimal values determined via ROC curve analysis. When used in conjunction with ESR and CRP, there was a statistically significant increase in the diagnostic performance of the model used to assess PJI relative to the model that just employed ESR and CRP (P < .05).ConclusionOur study demonstrates that platelets and their associated serum biomarkers are associated with PJI and warrant consideration in patients who are being evaluated for potential PJI.