Aim. The aim of the study is to evaluate the specificity and sensibility of leukocyte esterase for the diagnosis of periposthetic joint infection (PJI). Method. Between October 2016 and April 2017 we enrolled 65 patients underwent to hip and knee revision arthroplasty due to uncertain joint infection. Synovial fluid was obtained from 64 joints that underwent revision arthroplasty. Each patient was evaluated in the preoperative time with CRP, ESR and leukoscan, in the intraoperative time with frozen section and leukocyte esterase strip and post-operative with sonication fluid culture, periprosthetic tissues cultures and histological examination. Results of all of these exams were compared to assess the specificity, the sensibility, the positive and negative predicting values of leukocyte esterase for the diagnosis of PJI. Results. The leukocyte esterase test with a threshold of +/++ had a sensitivity of 80.2%, a specificity of 82.8%, a positive predictive value of 63.8%, and negative predictive value of 92.1%. Using the threshold of ++ as a positive leukocyte esterase result, the specificity reached 97.8%, the positive predictive value 90.8%, and the negative predictive value 89.0%. Conclusions. These results demonstrate that leukocyte esterase is a quite accurate, effective marker of periprosthetic joint infection and that it is a valuable tool that can be used in conjunction with the the other tests for diagnosis of PJI

Culture examination is still considered the gold standard for diagnosis of bone and joint infections, including prosthetic ones, even if in up to 20–30% of cases, particularly prosthetic joint infections, it fails to yield microbial growth. To overcome this limitation, determination of markers of inflammation and or infection directly in joint fluid has been proposed. Aim of this study was to evaluate the applicability of measurement of lecukocyte esterase (LE), C-reactive protein (CRP) and glucose in synovial fluid for diagnosis of bone and joint infections. Synovial fluids from 80 patients were aseptically collected and sent to laboratory for microbiological cultures. After centrifugation at 3000 rpm for 10 minutes, pellet was used for cultures, while the surnatant was used for determination of LE, CRP and glucose. LE and glucose were evaluated by means of enzymatic colorimetric strips developed for urinanalysis. One drop of synovial fluid was placed on the LE and on the glucose pads and the results were read after about 120 seconds. A LE test graded + or ++, and a glucose test equal to trace or negative were considered suggestive for infection. CRP was measured by an automated turbidimetric method. On the basis of clinical findings, microbiological, haematological and histological analyses patients were retrospectively divided into 2 groups. Group 1 comprised 19 infected patients (12 males, 7 females age: 70.6 ± 10.3 yrs, range: 47 – 88 yrs) while Group 2 included 61 aseptic patients (32 males and 29 females, age: 61.5 ± 16.3 yrs, range: 15 – 84). Sensitivity of the three tests was 89.5%. 84% and 73,7% for LE, CRP and glucose, respectively. Specificity was 98.4%, 88.5% and 70% for LE, CRP and glucose, respectively. Positive and negative predictive values were 94.4% and 96.8% for LE, 69.6% and 94.6% for CRP and 77.8% and 89.6% for glucose test. When LE was combined with CRP, sensitivity increased to 94.7%, while no differences were observed for LE combined with glucose. Leukocyte esterase has proven to be a rapid, simple and inexpensive test to rule in or out bone and joint infections. Combination of its measurement with that of CRP increased sensitivity. In conclusion, the combination of leukocyte esterase and CRP may represent a simple and useful tool for diagnosis of bone and joint infections

Aim. Septic arthritis (SA) is considered a medical emergency. The most common etiological agents are glucose consuming bacteria, so we evaluated the clinical utility of synovial fluid (SF) glucose levels and other biochemical parameters for supporting the diagnosis of the disease and their association with a positive bacteria culture and joint destruction. Methods. Adult patients with SA diagnose were enrolled prospectively between July 2018 and October 2019. As control group, adults with knee osteoarthritis, meniscus and/or knee ligaments lesions were enrolled. SF samples were obtained from the joints by arthrocentesis/arthrotomy. Microbiological analyses of SF were performed using Brucella broth blood culture flasks, samples were incubated at 37°C with 5% CO. 2. for 24 hours. Gram stain, chocolate and blood agar were used for the identification and growth of the bacteria. SF glucose levels, pH and leukocyte esterase were measured as biochemical parameters using a glucometer and colorimetric test strips. The Outerbridge classification was used for grading the osteochondral injury. Furthermore, blood samples were collected from patients and control subjects for determining glucose levels. Results. We included 8 subjects with knee ligaments lesions, 6 with meniscus lesions and 5 with osteoarthritis as control group, as well as 20 patients with SA diagnose. The mean age of the patients was 57.8 years with a 65% of male predominance. The most common affected joint was the knee (85%). SF culture was positive in 60% of the cases and the most common etiological agent was Staphylococcus aureus (58.3%). SF glucose levels from patients were lower than the controls (P=0.0018) and showed the lowest concentration in patients with a positive culture (P=0.0004). There was also a difference between blood and SF glucose concentration from the positive culture patients (P<0.0001). Leucocyte esterase presented the highest values in positive culture patients (P=<0.0001) and a more acidic pH was found compared to the control group (P<0.0001). Regarding the osteochondral injury, the lowest concentrations of SF glucose were found in patients with a higher grade in the classification (P = 0.0046). Conclusions. SF glucose and leukocyte esterase concentrations might be a quick and cheap useful parameter for the physician for distinguishing between bacterial infection and not infected joint. In addition, the lowest SF glucose levels might give information about the joint damage due to the disease

Aim. Diagnosing or excluding a chronic prosthetic joint infection (PJI) prior to revision surgery can be a clinical challenge. To enhance accuracy of diagnosis, several biomarkers were introduced in recent years, but most are either expensive or not available as a rapid test. We compared the diagnostic accuracy of leucocyte esterase (€0.20 per sample), calprotectin (€20 per sample) and alpha defensin (€200 per sample). Method. We prospectively evaluated PJI patients with chronic pain with or without prosthetic loosening between 2017 and 2018. Synovial fluid was collected prior to revision surgery. Leucocyte esterase was measured using a reagent strip (2+ considered as positive), and calprotectin and alpha defensin were measured using a lateral flow immunoassay. Intraoperative cultures (5 periprosthetic tissue samples, synovial fluid and sonication fluid) incubated for 9 days, were used as gold standard. At least two positive cultures of low-grade microorganisms with the same antibiogram were required to diagnose PJI. Results. A total of 19 patients were included (knee =11, hip =8). None of the patients were treated with antibiotics prior to revision surgery. A PJI was diagnosed in 8 patients (42.1%). The diagnostic accuracy of leucocyte esterase vs. calprotectin vs. alpha defensin was as follows; sensitivity 50.0% vs. 87.5% vs. 87.5%, specificity 81.8% vs. 90.9% vs. 100%, positive predictive value 60.0% vs. 87.5% vs. 100% and negative predictive value 75.0% vs. 90.9% vs. 91.6%, respectively. Both calprotectin and alpha defensin were false negative in one PJI caused by Cutibacterium acnes. The other two C. acnes PJIs were correctly diagnosed with both tests. Conclusions. Calprotectin is as accurate as alpha defensin in excluding a chronic PJI at 10% of the costs. Future studies with a large number of patients are necessary to analyze its diagnostic accuracy in very low-grade infections, in particularly caused by C. acnes

Aim. The analysis of synovial fluid has proved to be of crucial importance in the diagnostic process of prosthetic joint infections (PJI), suggesting the presence of an infection before the microbiological culture results. In this context, several studies illustrated the efficacy of synovial calprotectin in supporting the diagnosis of PJI [1, 2]. However, several testing methods have been explored to detect synovial calprotectin levels, emphasizing the need to use a standardized, rapid and rapid test. In this study, synovial calprotectin was analyzed by means of a commercial stool test [3] to explore whether the detected levels might predict PJIs and, therefore, being a promising tool for the fast and reliable diagnosis of this complication. Method. The synovial fluid of 55 patients underwent to revision of the prosthetic implant were analyzed. The measurement of calprotectin was carried out by of commercial stool test, following the protocol for liquid samples. Calprotectin levels were then compared to other synovial biomarkers of PJI such as leucocyte esterase and count and percentage of polymorphonuclear cells. Data analysis were performed using R software v4.1.1 (R Core Team) and package “pROC” [4]. Receiver operator characteristics curves were designed using culture test as gold standard to evaluate the area under curve (AUC) of each method (with DeLong method for confidence-interval calculation). Thresholds were calculated to maximize Youden's index; sensitivity and specificity were reported. One-to-one Pearson's correlations coefficient were calculated for each pair of methods. P value <0.05 were considered statistically significant. Results. Of the 55 synovial fluids analyzed, 13 patients were diagnosed with PJI and 42 with an aseptic failure of the implant. The specificity, sensitivity, and AUC of calprotectin resulted 0.90, 0.85, and 0.86 (95%CI: 0.72–0.99), respectively with a set threshold of 226.5 µg/g. The values of calprotectin had a moderate and statistically relevant correlation with the synovial leucocyte counts (r. s. = 0.54, p = 0.0003) and the percentage of polymorphonuclear cells (r. s. = 0.68, p = 0.0000). Conclusions. From this analysis, it can be concluded that synovial calprotectin is a valuable biomarker that correlates with other established indicator of local infection, delivering a rapid and reliable results and supporting the diagnostic process of PJI

Total knee arthroplasty (TKA) is one of the most common orthopaedic operations performed worldwide and it is largely successful in pain relief and functional recovery. However, when pain persists post-operatively the thorough evaluation must be instituted. Extra-articular causes of knee pain include; hip pathology, lumbar spine degenerative disease or radicular symptoms, focal neuropathy, vascular disease, and chronic regional pain syndrome. Intra-articular causes of knee pain: infection, crepitation/clunk, patella osteonecrosis, patella mal-tracking, soft tissue imbalance, malalignment, arthrofibrosis, component loosening, implant wear, ilio-tibial band irritation, and bursitis. Other causes of pain to rule out are component overhang with soft tissue irritation, recurrent hemarthrosis secondary to synovial impingement or entrapment, non-resurfaced patella, and metal sensitivity. A careful history may reveal previous knee surgeries with delayed healing or prolonged drainage, chronology of sign and symptoms, co-morbid medical conditions, jewel or metal sensitivity. Physical exam should help with specific signs in the operated knee. Targeted local anesthetic blocks are helpful and response to lumbar sympathetic blocks determines presence of CRPS. Lab tests are important: ESR, CRP, WBC, aspiration with manual cell count and diff, leucocyte esterase dipstick, RA titers, metal derm patch testing, nuclear scans, CT best for rotational malalignment, and MARS MRI. More recently patient satisfaction as an outcome measure has shown TKA results not satisfactory in 11- 18% of patients. A discordance of patient vs. surgeon satisfaction exists so the following factors may help improve this: correct patient selection, establishing and correlating surgeon-patient expectations, peri-operative optimization of patient co-morbidities to help avoid preventable complications, use of pre-operative and post-operative pathways. Satisfaction rates can best be improved by addressing the previous points with patients prior to TKA surgery

TKA is one of the most common orthopaedic operations performed worldwide and it is largely successful in pain relief and functional recovery. However, when pain persists post-operatively the thorough evaluation must be instituted. Extra-articular causes of knee pain include; hip pathology, lumbar spine degenerative disease or radicular symptoms, focal neuropathy, vascular disease, and chronic regional pain syndrome. Intra-articular causes of knee pain: infection, crepitation/ clunk, patella osteonecrosis, patella mal-tracking, soft tissue imbalance, malalignment, arthrofibrosis, component loosening, implant wear, ilio-tibial band irritation, and bursitis. Other causes of pain to rule out are component overhang with soft tissue irritation, recurrent hemarthrosis secondary to synovial impingement or entrapment, non-resurfaced patella, and metal sensitivity. A careful history may reveal previous knee surgeries with delayed healing or prolonged drainage, chronology of sign and symptoms, co-morbid medical conditions, jewel or metal sensitivity. Physical exam should help with specific signs in the operated knee. Targeted local anesthetic blocks are helpful and response to lumbar sympathetic blocks determines presence of CRPS. Lab tests are important: ESR, CRP, WBC, aspiration with manual cell count and diff, leukocyte esterase dipstick, RA titers, metal derm patch testing, nuclear scans, CT best for rotational malalignment,, and MARS MRI. More recently patient satisfaction as an outcome measure has shown TKA results not satisfactory in 11 – 18% of patients. A discordance of patient vs. surgeon satisfaction exists so the following factors may help improve this: correct patient selection, establishing and correlating surgeon-patient expectations, peri-operative optimisation of patient comorbidities to help avoid preventable complications, use of pre- and post-operative pathways. Satisfaction rates can best be improved by addressing the previous points with patients prior to TKA surgery

Aim. Alpha-defensin was recently introduced as a new biomarker having a very high accuracy to rule out periprosthetic joint infection (PJI). A new rapid lateral flow version of the Alpha-defensin test was developed and introduced to detect high levels of Alpha-defensin in synovial fluid quickly and with ease. We conducted a single-centre prospective clinical study to compare the results of the Alpha-defensin rapid test* against the conventional diagnostics according to MSIS criteria. Method. A total of 223 consecutive patients with painful total hip or knee arthroplasty were enrolled into the study. In all patients, blood C-reactive protein was measured and joint aspirations were performed. From the synovial fluid a leukocyte cell count with granulocyte percentage, microbiology cultures and Leukocyte Esterase tests were carried out according to the recommendation of MSIS for diagnosing PJI. At the same time, the Lateral Flow Test* was performed from the aspirate. 191 subjects with 195 joint aspirations (96 hips, 99 knees) were included in final clinical and statistical evaluation. We had 119 joints with an aseptic revision and 76 joints with PJI. Results. After statistical analysis the overall sensitivity of the Lateral Flow Test* was 92.1% (95% confidence interval [CI], 83.6% to 97.1%), the specificity was 100% (95% CI, 97.0% to 100%), the positive predictive value was 100% (95% CI, 94.9% to 100%), and the negative predictive value was 95.2% (95% CI, 89.9% to 98.2%). The overall accuracy of the Lateral Flow Test* was 96.9% (189 of 195, 95% CI, 93.4% to 98.9%). Conclusions. Our results suggest that the PJI test* has a very high accuracy in diagnosing infected THA and TKA. Though the Lateral Flow Test* does not provide information on the identity of the infectious pathogen, the test does have an important role in recognizing PJI early and enables surgeons to start proper therapy without delay. *Synovasure®

The AAOS clinical practice guideline for diagnosis of periprosthetic joint infection (PJI) and the MSIS definition of PJI were both “game changers” in terms of diagnosing PJI and the reporting of outcomes for research. However, the introduction of new diagnostic modalities, including biomarkers, prompted a re-look at the diagnostic criteria for PJI. Further there was a desire to develop an evidence-based, validated algorithm for the diagnosis of PJI. This multi-institutional study led by Dr. Jay Parvizi examined revision total joint arthroplasty patients from three academic institutions. For development of the algorithm, infected and aseptic cohorts were defined. PJI cases were defined using only the major criteria from the Musculoskeletal Infection Society (MSIS) definition (n=684). Aseptic cases underwent revision for a non-infective indication and did not show evidence of PJI or undergo a reoperation for any reason within 2 years (n=820). Risk factors, clinical findings, serum and synovial markers as well as intraoperative findings were assessed. A stepwise approach using random forest analysis and multivariate regression was used to generate relative weights for each of the various variables assessed at each stage to create an algorithm for diagnosing PJI using the 3 most important tests from each step. The algorithm was formally validated on a separate cohort of 422 patients, 222 who were treated with a 2-stage exchange for PJI who subsequently failed secondary to PJI within one year and 200 patients who underwent revision surgery for an aseptic diagnosis and had no evidence of PJI within two years and did not undergo a reoperation for any reason. The first step in evaluating PJI should include a physical examination to identify a sinus tract, followed by serum testing for C-reactive protein (cut-off value 1mg/dl), D-dimer (cut-off value 860ng/mL) and/or erythrocyte sedimentation rate (cut-off value 30mm/hr) in that order of importance. If at least one of these are elevated, or if there is a high clinical suspicion, joint aspiration should be performed, sending the fluid obtained for a synovial fluid white blood-cell (cut-off value 3,000 wbc/uL) or leukocyte esterase strip testing, polymorphonuclear percentage (cut-off value 80%) and culture. Alpha defensin did not show added benefit as a routine diagnostic test. Major diagnostic criteria are the same whereby the presence of a sinus tract or (2) positive cultures showing the same organism defines PJI. Special care should be taken in cases of ALTR (failed metal-on-metal bearing), crystalline deposition disease, inflammatory arthritis flares or slow growing organisms. In the rare cases where no fluid is obtained at the time of an attempted aspiration and revision surgery is not planned, then this is the rare scenario where nuclear imaging (my preference is an indium labeled white blood cell scan) or a biopsy can be performed. The updated definition of PJI demonstrated a higher sensitivity of 97.7% when compared to the MSIS criteria (79.3%) and the ICM definition (86.9%), with a similar specificity of 99.5%. However, just over 2% of patients examined do fall into the “inconclusive” category. The proposed diagnostic algorithm demonstrated a high overall sensitivity (96.9%) and specificity (99.5%)

Diagnosis of chronic prosthetic joint infection (PJI) is often challenging. Painful prosthesis is frequently due to an infection but to diagnose it is somethimes difficult. All recent guidelines stress the central role of joint punction in diagnosis of PJI if the infection is not demonstrated. However which test on synovial fluid must be carried out is not so clearly defined. Total white blood cell count and differential leukocite count are usually considered useful in diagnosis but cut offs reported by different studies are quite different. Moreover this test needs a relatively large amount of fluid and blood contamination of it largely affects the result. What's more the synovial fluid WBC count may be unreliable in the setting of a metal-on-metal bearing or corrosion reaction. Routine cultures should be maintained between 5 and 14 days, their sensitivity appears low in chronic infection even if witholding antimicrobial therapy before the collection of the fluid can increase the likelihood of recovery an organism. Synovial leukocyte esterase can be performed as a rapid office or intraoperative point of care test using urinalysis strips. It is cheap and easy to perform, but the presence of blood in the sample can affect the result and it needs centrifugation. Recently a new test has been proposed to detect alfa-defensine in synovial fluid. It shows a high sensitivity and an exellent specificity. We performed 25 joint punctions on 25 patients with suspected PJI (enrollment is going on). Synovial fluid collected was tested for: leukocite esterase, WBC count and differential, colture in blood colture bottle for anerobe and aerobes (BacT/ALERT Biomerieux, inc) and detection of alfa-defensine level (Synovasure – Zimmer). In patients who underwent surgery at least 5 samples of periprotesic tissue were collected for microbiologic analysis and the removed implant was sonicated according with the methodic. Furthermore samples for frozen section were sent and a histologic examination was made according to the Moriewitz – Kerr classification. The MSIS criteria was utilized to classify the case as infected or not

Periprosthetic joint infection (PPJI) following shoulder arthroplasty is uncommon, with an overall rate of 0.98%. However, the rates following revision arthroplasty and reverse arthroplasty are much higher. Given the rapid increase in the prevalence of shoulder arthroplasty and the increasing revision burden, the cost of PPJI to society will likely increase substantially. The most common organisms found in PPJI following shoulder arthroplasty are Staphylococcus aureus, coagulase-negative Staphylococcus, and Propionibacterium acnes (P. acnes). P. acnes is especially common in males. Traditional testing for PPJI includes aspiration, white blood cell count (WBC), erythrocyte sedimentation rate (ESR), and c-reactive protein (CRP). Aspiration often yields a dry tap and when fluid is obtained for culture, a positive result is helpful but a negative result does not rule out PPJI. Although WBC, ESR, and CRP are often positive with PPJI in the lower extremity, they are most often negative in shoulder PPJI. Although bone scans and WBC labeled scans are used, they are expensive and have low sensitivity and specificity. New testing and techniques have been reported in an attempt to improve sensitivity and specificity for PPJI. These techniques can be divided into tests on serum, synovial fluid, and tissue. Serum Interleukin-6 (IL-6) is highly specific (94%) for shoulder PPJI but has low sensitivity (14%). Synovial fluid can be tested for leukocyte esterase using a simple and cheap technique. In lower extremity PPJI it has shown to be helpful. It is not as helpful in shoulder PPJI with 30% sensitivity and 67% specificity. Alpha defensin has been reported to be more sensitive (63%) and as specific (95%) as traditional techniques but still lacks predictive value. Testing for specific cytokines (IL-2, IL-6, TNF- α) within synovial fluid is not widely used as yet but has shown promise with 80% sensitivity and 90% specificity. Obtaining tissue for culture and other testing is probably the most reliable way of confirming PPJI for the shoulder. Frozen sections taken at the time of revision can be helpful but is very pathologist dependent and institution specific. With a dedicated musculoskeletal pathologist, the finding of 10 or more WBCs per high powered field has been reported to be 72% sensitive and 100% specific for P. acnes and 63% sensitive and 100% specific for other organisms. Cultures from arthroscopic tissue biopsy have also been found to have high sensitivity (100%) and specificity (100%). Genetic testing of tissue biopsy specimens (PCR/NGS) has recently been reported and shows great promise. The significance of positive cultures and other tests, especially for P. acnes is unclear. There is a high rate of positive intra-operative cultures in primary cases of shoulder arthroplasty. In addition, intra-operative cultures taken at the time of revision, even in cases in which infection is not suspected, are frequently positive for P. acnes with weak correlation with rates of post-operative clinical infection. In conclusion, shoulder PPJI is a difficult problem to deal with. The definition of shoulder PPJI is currently unclear and further study is needed. There is no ideal test to confirm it. A reasonable approach is to aspirate for culture, and perform serum tests for WBC, ESR, and C-reactive protein. If any of these is positive in the setting of a painful arthroplasty, PPJI should be assumed until proven otherwise. Operative tissue cultures are probably the most reliable test but the clinical significance is not always obvious. Synovial fluid cytokine profiles and tissue PCR/NGS show promise for the future

Aims

The aim of this study was to analyze the prevalence of culture-negative periprosthetic joint infections (PJIs) when adequate methods of culture are used, and to evaluate the outcome in patients who were treated with antibiotics for a culture-negative PJI compared with those in whom antibiotics were withheld.

Periprosthetic joint infection (PJI) complicates between 0.5% and 1.2% primary total hip arthroplasties (THAs) and may have devastating consequences. The traditional assessment of patients suffering from PJI has involved the serological study of inflammatory markers and microbiological analysis of samples obtained from the joint space. Treatment has involved debridement and revision arthroplasty performed in either one or two stages.

We present an update on the burden of PJI, strategies for its diagnosis and treatment, the challenge of resistant organisms and the need for definitive evidence to guide the treatment of PJI after THA.

Cite this article: Bone Joint J 2016;98-B(1 Suppl A):27–30.