The Diagnostic Utility of Fast Tests for Detecting C-Reactive Protein in Synovial Fluid in Periprosthetic Joint Infections.

BACKGROUND: Despite the fact that many synovial fluid biomarkers have found application in the routine diagnosis of periprosthetic joint infection (PJI), this process still remains a challenge for orthopaedic surgeons. To simplify this process, fast point-of-care (POC) tests can be used during ambulatory visits and in operating room conditions. However, before such tests can be routinely used in clinical practice, they require validation. The purpose of the present study was to evaluate the diagnostic accuracy of different fast POC tests for detecting C-reactive protein (CRP) in synovial fluid for the diagnosis of PJI. METHODS: Synovial fluid samples were collected from 120 consecutive patients who underwent revision total joint arthroplasty (TJA). The patients were divided into 2 groups. The first group included 76 patients who underwent revision for reasons other than infection (the aseptic revision TJA [arTJA] group), and the second group included 44 patients who underwent revision because of periprosthetic joint infection (PJI). The diagnosis of infection was made according to the International Consensus Meeting (ICM) 2018 criteria. All patients were operatively treated at a single orthopaedic center from January 2022 to February 2023. Four fast CRP tests with different cutoff values (1 and 3 mg/L, ≥8 mg/L, ≥10 mg/L [cassette], ≥10 mg/L [strip]) were used off-label for synovial fluid testing. Tests were performed on the same synovial fluid samples, and the results of these tests were compared with those obtained with the laboratory method. RESULTS: The cassette test with a minimum cutoff value of ≥8 mg/L demonstrated the best accuracy for the diagnosis of chronic PJI, with a sensitivity and specificity of 90.9% and 90.8%, respectively. For the cassette test with a cutoff value of >3 mg/L, the sensitivity and specificity were 68.2% and 77.6%, respectively. For the tests with a minimum cutoff value of ≥10 mg/L, the sensitivity and specificity were 77.3% and 94.7%, respectively, for the cassette test and 77.3% and 96.1%, respectively, for the strip test. The laboratory method with the statistically calculated threshold (2.7 mg/L) revealed the highest AUC (area under the receiver operating characteristic curve) value (0.95), with 90.9% sensitivity and 94.7% specificity. CONCLUSIONS: The cassette POC test with the minimum cutoff value of ≥8 mg/L had very good accuracy for the diagnosis of chronic PJI. This test had comparable sensitivity and slightly lower specificity in comparison with the laboratory method with the calculated threshold of 2.7 mg/L. LEVEL OF EVIDENCE: Diagnostic Level III . See Instructions for Authors for a complete description of levels of evidence.

What is the Accuracy of a Rapid Strip Test That Detects D-lactic Acid in Synovial Fluid for the Diagnosis of Periprosthetic Joint Infections?

BACKGROUND: D-lactic acid is a specific marker produced almost exclusively by bacterial species; thus, the appearance of this marker in synovial fluid may indicate periprosthetic joint infection (PJI). Recently, studies have investigated the accuracy of enzyme-linked laboratory tests that detect D-lactic acid in synovial fluid to diagnose PJI. However, to our knowledge, no studies have determined the usefulness of rapid strip tests that detect D-lactic acid in synovial fluid in the diagnosis of PJI. QUESTIONS/PURPOSES: (1) What is the best cutoff value for the rapid D-lactic acid strip test for diagnosing PJI? (2) What are the diagnostic accuracies (sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]) of the rapid D-lactic acid strip test and two different rapid leukocyte esterase (LE) strip tests? METHODS: This prospective study enrolled 157 patients who underwent revision THA or TKA from May 2021 to February 2022 at a single orthopaedic center. Seventy percent (110 of 157) were eligible for analysis; 10% of these patients (15 of 157) were excluded based on the exclusion criteria (causes of revisions and additional comorbidities that may interfere with the results), and 20% (32 of 157) of the synovial fluid samples could not be tested (dry taps and blood-contaminated samples that could not be centrifuged). We performed the following off-label diagnostic tests on synovial fluid samples collected from all patients: the D-lactic acid strip test (QuantiQuick TM , BioAssay System), two different LE strip tests (10 EA from ARKRAY and BM 10 from BioMaxima). Differently colored strips were marked with symbols (from [-] to [++++] for D-lactic acid and from [-] to [+++] for LE tests) according to the manufacturers' instructions. For the LE tests, results were different for (++), which corresponds to a minimal value of 250 leu/mL for 10 EA and 125 leu/mL for BM 10 tests. The diagnostic standard for the presence or absence of PJI in this study was the International Consensus Meeting (ICM) 2018 criteria; based on these criteria (without the application of an LE test as a minor criterion), all patients were assessed and divided into two groups. Patients who did not meet the criteria for PJI and underwent revision for aseptic loosening, implant malposition, instability, or implant damage were included in the aseptic revision total joint arthroplasty group (68 patients). Patients with a fistula penetrating the joint, those with two positive culture results of the same pathogen, or those with ≥ 6 points according to ICM 2018 minor criteria were enrolled in the PJI group (42 patients). To ascertain the best cutoff value for the rapid D-lactic acid and both LE strip tests for diagnosing PJI, we used collected results, generated a receiver operating characteristic curve, and calculated the Youden index. To determine the accuracies of the diagnostic tests, we calculated their sensitivities, specificities, PPVs, and NPVs against the diagnostic standard (the ICM 2018 criteria). RESULTS: The best cutoff value for D-lactic acid was 22.5 mg/L, which corresponded to a reading of (+) on the test strip. For D-lactic acid, in the diagnosis of PJI, the sensitivity was 83% (95% confidence interval [CI] 68% to 92%) and specificity was 100% (95% CI 93% to 100%). For both LE strip tests, the best cutoff value was the same as that proposed in the ICM 2018 criteria. For LE (10 EA), the sensitivity was 81% (95% CI 66% to 91%) and specificity was 99% (95% CI 91% to 100%); for LE (BM 10), sensitivity was 81% (95% CI 65% to 91%) and specificity was 97% (95% CI 89% to 100%). CONCLUSION: A rapid off-label D-lactic acid strip test is valuable for diagnosing PJI. The results of this study indicate very good accuracy with comparable sensitivity and specificity for both LE strip tests. The usefulness of the test in a group of patients with chronic inflammatory diseases and the reproducibility of the reading by different researchers were not analyzed in this study and require further investigations. Before a rapid D-lactic strip test is routinely used for diagnosing PJI, multicenter studies on a larger group of patients should be conducted.Level of Evidence Level II, diagnostic study.

Periprosthetic Joint Infections Caused by Candida Species-A Single-Center Experience and Systematic Review of the Literature.

BACKGROUND: The aim of this study was to analyze the treatment results of fungal periprosthetic joint infections (PJI) caused by Candida species from a single orthopedic center and to compare them with reports from other institutions. METHODS: Eight patients operated on from January 2014 to December 2021 met the inclusion criteria and were analyzed in terms of clinical outcomes. A systematic review of the literature identified 153 patients with Candida PJIs extracted from 12 studies according to the PRISMA (Preferred Reporting Item for Systematic Reviews and Meta-Analyses) guidelines. RESULTS: The success rate of the treatment in the case series was 50%. The most frequent pathogens were Candida albicans (three cases; 37.5%) and Candida parapsilosis (three cases; 37.5%). In one patient (12.5%), bacterial co-infection was noted, and in five patients (62.5%) significant risk factors of PJI were confirmed. The overall success rate on the basis of data collected for systematic review was 65.5%. A sub-analysis of 127 patients revealed statistically significant differences (p = 0.02) with a higher success rate for the knees (77.6%) than for the hips (58%). In 10 studies the analysis of risk factors was performed and among 106 patients in 77 (72.6%) comorbidities predispose to fungal PJI were confirmed. Bacterial co-infection was noted in 84 patients (54.9%). In 93 patients (60.7%) Candida albicans was the culprit pathogen, and in 39 patients (25.5%) Candida parapsilosis was the culprit pathogen. Based on these two most frequent Candida species causing PJI, the success rate of the treatment was statistically different (p = 0.03), and was 60.3% and 83.3%, respectively. The two-stage strategy was more favorable for patients with Candida parapsilosis infections (94.4% success rate) than the one-stage protocol (50% success rate; p = 0.02); as well as in comparison to the two-stage treatment of Candida albicans (65% success rate; p = 0.04). CONCLUSIONS: The analysis of the literature showed no differences in the overall success rate between one- and two-stage surgical strategies for all Candida species, but differed significantly comparing the two most frequent strains and concerning PJI localization. The frequent presence of bacterial co-infections makes it necessary to consider the additional administration of antibiotics in the case of fungal PJI.

Blood and synovial fluid calprotectin as biomarkers to diagnose chronic hip and knee periprosthetic joint infections.

AIMS: Calprotectin (CLP) is produced in neutrophils and monocytes and released into body fluids as a result of inflammation or infection. The aim of this study was to evaluate the utility of blood and synovial CLP in the diagnosis of chronic periprosthetic joint infection (PJI). METHODS: Blood and synovial fluid samples were collected prospectively from 195 patients undergoing primary or revision hip and knee arthroplasty. Patients were divided into five groups: 1) primary total hip and knee arthroplasty performed due to idiopathic osteoarthritis (OA; n = 60); 2) revision hip and knee arthroplasty performed due to aseptic failure of the implant (AR-TJR; n = 40); 3) patients with a confirmed diagnosis of chronic PJI awaiting surgery (n = 45); 4) patients who have finished the first stage of the PJI treatment with the use of cemented spacer and were qualified for replantation procedure (SR-TJR; n = 25), and 5) patients with rheumatoid arthritis undergoing primary total hip and knee arthroplasty (RA; n = 25). CLP concentrations were measured quantitatively in the blood and synovial fluid using an immunoturbidimetric assay. Additionally, blood and synovial CRP, blood interleukin-6 (IL-6), and ESR were measured, and a leucocyte esterase (LE) strip test was performed. RESULTS: Patients with PJI had higher CLP concentrations than those undergoing aseptic revision in blood (median PJI 2.14 mg/l (interquartile range (IQR) 1.37 to 3.56) vs AR-TJR 0.66 mg/l (IQR 0.3 to 0.83); p < 0.001) and synovial fluid samples (median PJI 20.46 mg/l (IQR 14.3 to 22.36) vs AR-TJR 0.7 mg/l (IQR 0.41 to 0.95); p < 0.001). With a cut-off value of 1.0 mg/l, blood CLP showed a sensitivity, specificity, positive predictive value, and negative predictive value of 93.3%, 87.5%, 89.4%, and 92.1%, respectively. For synovial fluid with a cut-off value of 1.5 mg/l, these were 95.6%, 95%, 95.5%, and 95%, respectively. CONCLUSION: This small study suggests that synovial and blood CLP are useful markers in chronic PJI diagnosis with similar or higher sensitivity and specificity than routinely used markers such as CRP, ESR, IL-6, and LE. CLP was not useful to differentiate patients with PJI from those with rheumatoid arthritis. Cite this article: Bone Joint J 2021;103-B(1):46-55.

Elevated plasma D-dimer concentration has higher efficacy for the diagnosis of periprosthetic joint infection of the knee than of the hip-A single-center, retrospective study.

The aim of this study is to evaluate the value of D-dimers in the diagnosis of periprosthetic joint infection (PJI). The analysis was performed for revision total hip (rTHA) and revision total knee arthroplasty (rTKA) together and separately with two thresholds, one calculated by statistical methods and the second adopted from the ICM 2018 definition. The study group comprised 133 patients who underwent rTHA or rTKA: 68 patients diagnosed according to the ICM 2018 definition (PJI group) and 65 with aseptic implant loosening, instability, malposition, or implant failure with the exclusion of infection (aseptic revision total joint arthroplasty or arTJA group). Mean D-dimer concentrations were 0.36 ± 0.25 µg/ml in the arTJA group and 0.87 ± 0.78 µg/ml in the PJI group (p < .001). For rTHA and rTKA together, the sensitivity and specificity of the evaluation were 75% and 73.8% according to the calculated cut-off value (0.45 µg/ml), and 33.8% and 95.4% based on the ICM 2018 threshold (0.85 µg/ml). Separately, for rTHA, sensitivity and specificity were 62.5% and 62.1% for the calculated value (0.43 µg/ml) and 6.3% and 96.6% for the ICM 2018 threshold; for rTKA, sensitivity was 86.1% and specificity was 88.9% for the calculated threshold (0.48 µg/ml) and 58.3% and 94.4% for the ICM 2018 value. Our findings indicate that plasma D-dimers have potential as markers of knee PJI, but moderate to low value for hip PJI.

Ultrasound frequency of sonication applied in microbiological diagnostics has a major impact on viability of bacteria causing PJI.

OBJECTIVES: Sonication of explanted prosthesis constitutes an element of microbiological diagnostics. The aim of performing this procedure is to remove biofilm and to increase sensitivity of diagnostics. Ultrasound used in medical purposes are low-frequency and low-intensity. With this wide range of frequency which can be used in sonication process it is necessary to find the golden mean between biofilm dislodging and planktonic bacteria sparing. MATERIALS AND METHODS: The aim of this study was to determine the least harming low-intensity ultrasound frequency (35 kHz, 40 kHz or 53 kHz) used during sonication process with other parameters constant. Four bacteria species were examined: S. aureus, E. faecalis, E. coli, K. pneumoniae. Number of microbiological studies (n) for each group (g) counted 40 specimens (based on scheme 1 bacteria type - 4 groups, 40 studies each). RESULTS: A detailed analysis of gathered data was conducted. Based on study findings following conclusions were drawn. Sonication has a significant and negative impact on survival of sonicated planktonic bacteria. Part of bacteria in planktonic state are damaged/killed by ultrasound, which is demonstrated by lower CFU count in sonicated samples versus control group. CONCLUSIONS: Optimal ultrasound frequencies for sonication of S. aureus, P. aeruginosa and E. coli are 35 kHz and 40 kHz. Ultrasound frequencies used in sonication process (35 kHz, 40 kHz, 53 kHz) of E. coli showed same impact on bacteria survival. It is crucial to perform further assessment of ultrasound parameters on clinical effects of sonication used in PJI diagnostics.

A Retrospective Analysis of Bacteriological Studies of Surgical Site Infections in a Monoprofile, Multidepartmental Orthopedic Hospital.

BACKGROUND: Despite improvements in surgical techniques, aseptics and prevention of infections, hospital surgical site infections (SSI) still remain one of the main reasons for failure in therapeutic musculoskeletal surgery. This study aimed to conduct a retrospective analysis of microbiological examinations and determine pathogen sensitivity to antibiotics as the basis for selecting methods for preventing and treating complicating infections. MATERIAL AND METHODS: The study is a retrospective analysis of bacteriological tests performed in the departments of the Public Clinical Hospital of the Medical Centre of Postgraduate Education in Otwock. Importantly, our monoprofile hospital specialising in musculoskeletal pathology is a reference centre, admitting patients from the entire country. Often these are patients transferred from Intensive Care Units at other hospitals with internally infected local emergencies (infections with local, complex, multidrug resistant bacterial flora). Bacteriological mapping of the hospital covered the period from 2009 to 2013 to indicate so called "strategic departments" demonstrating the most complex multidrug-resistant bacterial flora. Surgical site infections were managed by surgery with targeted antibiotic therapy. RESULTS: Analysis of patients' profiles revealed that SSIs detected across hospital departments in SPSK CMKP in Otwock mostly came from other medical centers where patients were initially hospitalized. The Osteomyelitis Department and the Department of Pelvic Pathology and Traumatology were identified as "strategic departments". CONCLUSIONS: 1. The analysis indicated that methicillin-sensitive Staphylococcus aureus (MSSA) was the most common pathogen responsible for complicating infections in our hospital. 2. The percentage of bacterial resistance to methicillin signifi -cantly increased in patients with multi-organ injuries who had previously been hospitalized at other centres. 3. Credible prevention and diagnosis of inflammatory risk factors in the preoperative period was of key importance in reducing the percentage of complicating infections.

The effects of cooperation between orthopaedic surgeons and microbiologists on the effectiveness of diagnosis and treatment of septic hip joint loosening.

BACKGROUND: The objective of this study is to compare the results of microbiological examinations of two types of materials: specimens collected intraoperationally upon removal of prostheses following septic loosening and cultures from sonicated implants. The study was the effect of collaboration between the Clinic of Orthopedics of A. Gruca Hospital in Otwock and the Department of Microbiology in Lublin. MATERIAL AND METHODS: The study population consisted of 24 patients aged 39 to 84 years, average of 68 years, undergoing surgeries at the Department of Bone and Joint Inflammation, Clinic of Orthopedics of A. Gruca Hospital in Otwock in years 2010-2011. All patients were qualified for surgical treatment consisting of removal of hip prosthesis due to inflammation. Sixty percent of the group were women, while the remaining forty percent were men. The methodology of the study was based on intraoperational collection of material for microbiological examinations at the Department of Microbiology of A. Gruca Hospital. The study material was collected from 3 locations: femoral shank, hip acetabulum and gluteal muscle. Explanted implants were placed in sterile containers, frozen at -20°C and transported to the Department of Microbiology in Lublin. There, the implants were sonicated. RESULTS: The obtained results were consistent in both groups in 37% of cases. In 9 patients (37%), standard cultures were negative while the cultures of sonicated material were positive. In 16 patients (67%), the spectrum of perioperative and sequential antibiotic therapy included flora cultured by standard methods as well as flora obtained from sonicated implant cultures. In the remaining patients, cultures obtained from sonicated material were resistant to antibiotics used. CONCLUSIONS: Cultures of sonicated implant materials increase the chance for identification of microbes responsible for inflammation. Limitations of the method include the requirement to either examine the implant shortly after removal or freeze the implant in order to prevent secondary infections of the material.