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.     

Definition of Periprosthetic Joint Infection: Is There a Consensus?

Background  

The diagnosis of periprosthetic joint infection (PJI) continues to pose a challenge. While many diagnostic criteria have been proposed, a gold standard for diagnosis is lacking. Use of multiple diagnostic criteria within the joint arthroplasty community raises concerns in patient treatment and comparison of research pertaining to PJI.     

How Reliable Is the Alpha-defensin Immunoassay Test for Diagnosing Periprosthetic Joint Infection? A Prospective Study

Clinical Orthopaedics and Related Research® - A key issue in the treatment of periprosthetic joint infection (PJI) is the correct diagnosis. The main problem is lack of diagnostic tools able...     

Is Treatment of Periprosthetic Joint Infection Improving Over Time?

BackgroundIt is unknown whether the outcomes of treatment for periprosthetic joint infection (PJI) are improving with time. This study evaluated trends in PJI treatment outcomes in the hip and knee following 2-stage exchange arthroplasty and irrigation and debridement (I&D) over the last 17 years.MethodsWe reviewed 550 two-stage exchange arthroplasties and 194 I&Ds between 2000 and 2016 at our institution. Treatment success was defined according to the Delphi consensus criteria and Kaplan-Meier survivorship curves were generated. A multivariate Cox proportional hazards regression model was generated to determine time trends in the outcome of PJI treatment with the year of surgery included as both a continuous covariate (per 1-year increase) and a categorical covariate (2000-2010 or 2011-2016).ResultsThe survivorship of I&D, 2-stage revision, and the total combined cohort were comparable between 2000-2010 and 2011-2016 groups. Multivariate Cox regression analysis showed that the year of surgery was not associated with treatment failure following an I&D or 2-stage exchange arthroplasty, and neither did it increase the risk of non-reimplantation. When year of surgery was considered as a categorical variable, there remained no significant difference in treatment failure following an I&D or 2-stage exchange arthroplasty between the 2000-2010 cohort and 2011-2016 cohort.ConclusionDespite the increasing clinical focus, research advances, and growing literature relating to PJI, we were unable to detect any substantial improvement in the treatment success rates of PJI at our institution over the 17 years examined in this study. Novel treatments and techniques are certainly needed as current and prior strategies remain far from optimal.     

CORR Insights®: How Reliable Is the Alpha-Defensin Immunoassay Test for Diagnosing Periprosthetic Joint Infection? A Prospective Study

Clinical Orthopaedics and Related Research® -     

Diagnosis of Periprosthetic Joint Infection—An Algorithm-Based Approach

Background

Periprosthetic joint infection (PJI) remains one of the most challenging and devastating modes of failure after total hip and knee arthroplasties. Despite the profound urgency and impact of PJI on an individual and societal basis, historically, there have not been standardized definitions of and diagnostic algorithms for infection after total joint arthroplasty.

Does Symptomatic Benign Prostatic Hyperplasia Increase the Risk of Periprosthetic Joint Infection After Primary Total Joint Arthroplasty?

BackgroundPeriprosthetic joint infection (PJI) is among the leading causes of failure in total joint arthroplasty. A recently proposed risk factor for PJI is symptomatic benign prostatic hyperplasia (sBPH). This study aims to determine if sBPH is associated with PJI following primary total hip arthroplasty (THA) and total knee arthroplasty (TKA).MethodsUsing the Mariner all-payer claims database, 1745 patients with sBPH undergoing primary THA were propensity-matched with 3490 controls, and 3053 patients with sBPH undergoing primary TKA were propensity-matched with 6106 controls. Additionally, the same 1745 patients with sBPH undergoing THA were compared to 317,360 prematched controls, and the same 3053 patients with sBPH undergoing TKA were compared to 557,730 prematched controls. Univariate analysis was conducted using chi-squared or ANOVA where appropriate.ResultsAt two years postoperatively, patients with sBPH were not at significantly increased risk for PJI following primary THA (1.54% vs 1.43%; P = .745) and TKA (1.99% vs 2.14%; P = .642) relative to postmatch controls. Compared to matched controls, THA patients with sBPH had an increased 90-day incidence of anemia (P < .001), blood transfusion (P < .001), and urinary tract infection (UTI; P < .001). Total knee arthroplasty patients with sBPH had an increased 90-day incidence of anemia (P < .001), blood transfusion (P < .001), cellulitis (P = .023), renal failure (P = .030), heart failure (P = .029), and UTI (P < .001) relative to matched controls.ConclusionIn primary THA and TKA, sBPH does not appear to be an independent risk factor for PJI within two years postoperatively. However, clinicians should be cognizant of the significantly increased risk for postoperative UTI in this patient population.     

Preoperative Anemia in Total Joint Arthroplasty: Is It Associated with Periprosthetic Joint Infection?

Background  

Anemia is common in patients undergoing total joint arthroplasty (TJA). Numerous studies have associated anemia with increased risk of infection, length of hospital stay, and mortality in surgical populations. However, it is unclear whether and to what degree preoperative anemia in patients undergoing TJA influences postoperative periprosthetic joint infection (PJI) and mortality.     

Articulating Knee Spacers in the Treatment of Periprosthetic Joint Infection: All Polyethylene Tibia or Tibial Insert?

BackgroundThe best antibiotic spacer for periprosthetic knee joint infection treatment is unknown. Using a metal-on-polyethylene (MoP) component provides a functional knee and may avoid a second surgery. Our study investigated complication rates, treatment efficacies, durabilities, and costs of MoP articulating spacer constructs using either an all-polyethylene tibia (APT) or a polyethylene insert (PI). We hypothesized that while the PI would cost less, the APT spacer would have lower complication rates and higher efficacies and durabilities.MethodsA retrospective review evaluated 126 consecutive articulating knee spacer (64 APTs and 62 PIs) cases from 2016 to 2020 was performed. Demographic information, spacer components, complication rates, infection recurrence, spacer longevity, and implant costs were analyzed. Complications were classified as follows: spacer-related; antibiotic-related; infection recurrence; or medical. Spacer longevity was measured for patients who underwent reimplantation and for those who had a retained spacer.ResultsThere were no significant differences in overall complications (P < .48), spacer-related complications (P = 1.0), infection recurrences (P = 1.0), antibiotic-related complications (P < .24), or medical complications (P < .41). Average time to reimplantation was 19.1 weeks (4.3 to 98.3 weeks) for APT spacers and 14.4 weeks (6.7 to 39.7 weeks) for PI spacers (P = .09). There were 31% (20 of 64) of APT spacers and 30% (19 of 62) of PI spacers that remained intact for an average duration of 26.2 (2.3 to 76.1) and 17.1 weeks (1.7 to 54.7) (P = .25), respectively, for patients who lived for the duration of the study. PI spacers cost less than APT ($1,474.19 versus $2,330.47, respectively; P < .0001).ConclusionAPT and PI tibial components have similar results regarding complication profiles and infection recurrence. Both may be durable if spacer retention is elected, with PI constructs being less expensive.     

Human Lung Stem Cells: Has the Future Arrived?

An intriguing paper was recently published that describes c-kit-positive human lung stem cells that self-renew and differentiate into multiple lineages. While these findings are potentially therapeutically exciting, several questions remain to be answered. We review the paper and the issues that have arisen.     

Infection Control Rate of Irrigation and Débridement for Periprosthetic Joint Infection

Background  

Irrigation and débridement with retention of prosthesis is commonly performed for periprosthetic joint infection. Infection control is reportedly dependent on timing of irrigation and débridement relative to the index procedure.     

Can the Leukocyte Esterase Strip Test Predict Persistence of Periprosthetic Joint Infection at Second-Stage Reimplantation?

BackgroundWe evaluated the reliability of intraoperative assessment of leukocyte esterase (LE) in synovial fluid samples from patients undergoing reimplantation following implant removal and spacer insertion for periprosthetic joint infection (PJI). Our hypothesis was that a positive intraoperative LE test would be a better predictor of persistent infection than either serum C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) or the combination of serum CRP and ESR.MethodsThe records of 76 patients who received a 2-stage exchange for PJI were retrospectively reviewed. Synovial fluid was collected for LE measurement during surgery before arthrotomy in 79 procedures. Receiver operating characteristic curves were generated. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the curve (AUC) of LE, CRP, ESR, and CRP + ESR were calculated.ResultsSensitivity, specificity, positive predictive value, and negative predictive value of the LE assay were 82%, 99%, 90%, and 97%, respectively. Receiver operating characteristic analysis revealed an LE threshold of 1.5 between the first (negative) and the second (positive) level of the ordinal variable, so that a grade starting from 1+ was accurate for a diagnosis of persistent infection (AUC 0.9044). The best thresholds for the CRP and the ESR assay were 8.25 mg/L (82% sensitivity, 84% specificity, AUC 0.8416) and 45 mm/h (55% sensitivity, 87% specificity, AUC 0.7493), respectively.ConclusionThe LE strip test proved a reliable tool to diagnose persistence of infection and outperformed the serum CRP and ESR assays. The strip test provides a valuable intraoperative diagnostic during second-stage revision for PJI.     

What Is the Optimal Timing for Reading the Leukocyte Esterase Strip for the Diagnosis of Periprosthetic Joint Infection?

BackgroundThe leucocyte esterase (LE) strip test often is used to diagnose periprosthetic joint infection (PJI). In accordance with the manufacturer’s directions, the LE strip test result is read 3 minutes after exposing it to joint fluid, but this has not been supported by robust research. Moreover, we have noted that the results of the LE strip test might change over time, and our previous studies have found that centrifugation causes the results of the LE strip test to degrade. Still, there is no evidence-based recommendation as to when to read the LE strip test to maximize diagnostic accuracy, in general, and the best reading times for the LE strip test before and after centrifugation need to be determined separately, in particular.Questions/purposes(1) What is the optimal timing for reading LE strip test results before centrifugation to diagnose PJI? (2) What is the optimal timing for reading LE strip test results after centrifugation to diagnose PJI?MethodsThis study was a prospective diagnostic trial. In all, 120 patients who were scheduled for revision arthroplasty and had signs of infection underwent joint aspiration in the outpatient operating room between July 2018 and July 2019 and were enrolled in this single-center study. For inclusion, patients must have had a diagnosis of PJI or nonPJI, valid synovial fluid samples, and must not have received antibiotics within 2 weeks before arthrocentesis. As such, 36 patients were excluded; 84 patients were included for analysis, and all 84 patients agreed to participate. The 2018 International Consensus Meeting Criteria (ICM 2018) was used for the classification of 49 patients with PJI (score ≥ 6) and 35 without PJI (score ≤ 2). The classification was used as the standard against which the different timings for reading LE strips were compared. All patients without PJI were followed for more than 1 year, during which they did not report the occurrence of PJI. All patients were graded against the diagnostic criteria regardless of their LE strip test results. In 83 patients, one drop of synovial fluid (50 μL) was applied to LE strips before and after centrifugation, and in one patient (without PJI), the sample was not centrifuged because the sample volume was less than 1.5 mL. The results of the strip test were read on an automated colorimeter. Starting from 1 minute after centrifugation, these strips were automatically read once every minute, 15 times (over a period of 16 minutes), and the results were independently recorded by two observers. Results were rated as negative, ±, 1+, and 2+ upon the machine reading. Grade 2+ (dark purple) was used as the threshold for a positive result. An investigator who was blinded to the study performed the statistics. Optimal timing for reading the LE strip before and after centrifugation was determined by using receiver operative characteristic (ROC) analysis. The specificity, sensitivity, and positive predictive and negative predictive values were calculated for key timepoints.ResultsBefore centrifugation, the area under the curve was the highest when the results were read at 5 minutes (0.90 [95% CI 0.83 to 0.98]; sensitivity 0.88 [95% CI 0.75 to 0.95]; specificity 0.89 [95% CI 0.72 to 0.96]). After centrifugation, the area under the curve was the highest when the results were read at 10 minutes (0.92 [95% CI 0.86 to 0.98]; sensitivity 0.65 [95% CI 0.50 to 0.78]; specificity 0.97 [95% CI 0.83 to 1.00]).ConclusionThe LE strip test results are affected by time and centrifugation. For samples without centrifugation, we found that 5 minutes after application was the best time to read LE strips. We cannot deny the use of centrifuges because this is an effective way to solve the sample-mingling problem at present. We recommend 10 minutes postapplication as the most appropriate time to read LE strips after centrifugation. Multicenter and large–sample size studies are warranted to further verify our conclusion.Level of EvidenceLevel II, diagnostic study.     

Periprosthetic Joint Infection: Are Patients With Multiple Prosthetic Joints at Risk?

Patients who present with a periprosthetic joint infection in a single joint may have multiple prosthetic joints. The risk of these patients developing a subsequent infection in another prosthetic joint is unknown. Our purposes were (1) to identify the risk of developing a subsequent infection in another prosthetic joint and (2) to describe the time span and organism profile to the second prosthetic infection. We retrospectively identified 55 patients with periprosthetic joint infection who had another prosthetic joint in place at the time of presentation. Of the 55 patients, 11 (20%) developed a periprosthetic joint infection in a second joint. The type of organism was the same as the first infection in 4 (36%) of 11 patients. The time to developing a second infection averaged 2.0 years (range, 0-6.9 years).     

Is Intraoperative Dexamethasone Utilization Associated With Increased Rates of Periprosthetic Joint Infection Following Total Joint Arthroplasty?

BackgroundIntraoperative dexamethasone can reduce postoperative pain and nausea following total knee (TKA) and total hip arthroplasty (THA). To the best of our knowledge, no study to date has been adequately powered to detect the risk of periprosthetic joint infection (PJI) from early dexamethasone exposure. This study aimed to assess PJI rates and complications in patients undergoing primary elective TKA and THA who received intraoperative dexamethasone.MethodsA national database was used to identify adults undergoing primary elective TKA and THA between 2015 and 2020. Patients who received intraoperative dexamethasone and those who did not were identified. The primary endpoint was 90-day risk of infectious complications. Secondary end points included thromboembolic, pulmonary, renal, and wound complications. Multivariate analyses were performed to assess the risk of all endpoints between cohorts. Between 2015 and 2020, 1,322,025 patients underwent primary elective TJA, of which 857,496 (64.1%) underwent TKA and 474,707 (35.9%) underwent TKA.ResultsIn patients who underwent TKA, dexamethasone was associated with lower risk of PJI (adjusted odds ratio: 0.87, 95% CI: 0.82-0.93, P < .001) as well as other secondary endpoints such as pulmonary embolism, deep vein thrombosis, and acute kidney injury. In patients who underwent THA, dexamethasone was associated with a lower risk of PJI (adjusted odds ratio: 0.80, 95% CI: 0.73-0.86, P < .001) as well as other secondary endpoints such as pulmonary embolism, deep vein thrombosis, acute kidney injury, and pneumonia.ConclusionIntraoperative dexamethasone was not associated with increased risk of infectious complications. The data presented here provide evidence in support of intraoperative dexamethasone utilization during primary TKA or THA.     

Is There an Optimal Cutoff for Aspiration Fluid Volume in the Diagnosis of Periprosthetic Joint Infection?

BackgroundThe diagnosis of periprosthetic joint infection is often challenging in the setting of low aspiration volumes, or in the presence of infection with a slow-growing organism. We sought to determine if an optimal threshold of aspiration fluid volume exists when cultures from the preoperative aspiration are compared to intraoperative cultures.MethodsAll revision total hip and knee arthroplasty procedures over 5 years at our institution were reviewed. Cases were excluded if they underwent joint lavage during aspiration, had an antibiotic spacer in place, were suspected of adverse local tissue reaction to metal debris, did not have an accurate aspiration volume recorded, or if there were no aspiration or operative cultures available. Receiver operating characteristic curves were used to evaluate aspiration volume for identifying cases with identical aspiration and culture results.ResultsA total of 857 revision cases were reviewed, among which 294 met inclusion criteria. There were 45 cases (15.3%) with discordant aspiration and operative cultures. The mean aspiration volume for identical cases was significantly higher than for discordant cases (19.1 vs 10.2 mL, P = .02). The proportion of slow-growing organisms was significantly greater among discordant compared to identical operative cultures (52.4% for discordant cases vs 8.2% for identical cases, P < .001). The optimal cutoff value for predicting identical cultures was 3.5 mL for typical organisms and 12.5 mL for slow-growing organisms.ConclusionAspiration cultures are more likely to correlate with intraoperative cultures with higher aspiration volumes, and the optimal aspiration volume is higher for slow-growing organisms.