Evaluation of synovial fluid neutrophil CD64 index as a screening biomarker of prosthetic joint infection

2020 ◽  
Vol 102-B (4) ◽  
pp. 463-469 ◽  
Author(s):  
Leilei Qin ◽  
Ning Hu ◽  
Xinyu Li ◽  
Yuelong Chen ◽  
Jiawei Wang ◽  
...  

Aims Prosthetic joint infection (PJI) remains a major clinical challenge. Neutrophil CD64 index, Fc-gamma receptor 1 (FcγR1), plays an important role in mediating inflammation of bacterial infections and therefore could be a valuable biomarker for PJI. The aim of this study is to compare the neutrophil CD64 index in synovial and blood diagnostic ability with the standard clinical tests for discrimination PJI and aseptic implant failure. Methods A total of 50 patients undergoing revision hip and knee arthroplasty were enrolled into a prospective study. According to Musculoskeletal Infection Society (MSIS) criteria, 25 patients were classified as infected and 25 as not infected. In all patients, neutrophil CD64 index and percentage of polymorphonuclear neutrophils (PMN%) in synovial fluid, serum CRP, ESR, and serum CD64 index levels were measured preoperatively. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were analyzed for each biomarker. Results Serum CD64 index showed no significant difference between the two groups (p = 0.091). Synovial fluid CD64 index and PMN% discriminated good differentiation between groups of PJI and aseptic failure with AUC of 0.946 (95% confidence interval (CI) 0.842 to 0.990) and 0.938 (95% CI 0.832 to 0.987) separately. The optimal threshold value of synovial CD64 index for the diagnosis of PJI was 0.85, with a sensitivity of 92.00%, a specificity of 96.00%, and diagnostic odds ratio (DOR) of 227.11. Conclusion The present study demonstrates that CD64 index in synovial fluid could be a promising laboratory marker for screening PJI. The cut-off values of 0.85 for synovial CD64 index has the potential to distinguish aseptic failure from PJI. Cite this article: Bone Joint J 2020;102-B(4):463–469.

2020 ◽  
Vol 9 (9) ◽  
pp. 587-592
Author(s):  
Leilei Qin ◽  
Xinyu Li ◽  
Jiawei Wang ◽  
Xuan Gong ◽  
Ning Hu ◽  
...  

Aims This study aimed to explore whether serum combined with synovial interleukin-6 (IL-6) measurement can improve the accuracy of prosthetic joint infection (PJI) diagnosis, and to establish the cut-off values of IL-6 in serum and synovial fluid in detecting chronic PJI. Methods Patients scheduled to have a revision surgery for indications of chronic infection of knee and hip arthroplasties or aseptic loosening of an implant were prospectively screened before being enrolled into this study. The Musculoskeletal Infection Society (MSIS) definition of PJI was used for the classification of cases as aseptic or infected. Serum CRP, ESR, IL-6, and percentage of polymorphonuclear neutrophils (PMN%) and IL-6 in synovial fluid were analyzed. Statistical tests were performed to compare these biomarkers in the two groups, and receiver operating characteristic (ROC) curves and area under the curve (AUC) were analyzed for each biomarker. Results A total of 93 patients were enrolled. There was no difference in demographic data between both groups. Synovial fluid IL-6, with a threshold of 1,855.36 pg/ml, demonstrated a mean sensitivity of 94.59% (95% confidence interval (CI) 81.8% to 99.3%) and a mean specificity of 92.86% (95% CI 82.7 to 98.0) for detecting chronic PJI. Then 6.7 pg/ml was determined to be the optimal threshold value of serum IL-6 for the diagnosis of chronic PJI, with a mean sensitivity of 97.30% (95% CI 85.8% to 99.9%) and a mean specificity of 76.79% (95% CI 63.6% to 87.0%). The combination of synovial IL-6 and serum IL-6 led to improved accuracy of 96.77% in diagnosing chronic PJI. Conclusion The present study identified that a combination of IL-6 in serum and synovial IL-6 has the potential for further improvement of the diagnosis of PJI. Cite this article: Bone Joint Res 2020;9(9):587–592.


Author(s):  
Amelia Staats ◽  
Peter W. Burback ◽  
Mostafa Eltobgy ◽  
Dana M. Parker ◽  
Amal O. Amer ◽  
...  

Bacterial infections of hip and knee implants are rare but devastating complications of orthopedic surgery. Despite a widespread appreciation of the considerable financial, physical, and emotional burden associated with the development of a prosthetic joint infection, the establishment of bacteria in the synovial joint remains poorly understood.


2021 ◽  
Vol 6 (4) ◽  
pp. 91-97
Author(s):  
F. Ruben H. A. Nurmohamed ◽  
Bruce van Dijk ◽  
Ewout S. Veltman ◽  
Marrit Hoekstra ◽  
Rob J. Rentenaar ◽  
...  

Abstract. Introduction: Debridement, antibiotics and implant retention (DAIR) procedures are effective treatments for acute postoperative or acute hematogenous periprosthetic joint infections. However, literature reporting on the effectiveness of DAIR procedures performed after a one- or two-stage revision because of a prosthetic joint infection (PJI) (PJI-related revision arthroplasty) is scarce. The aim of this study is to retrospectively evaluate the infection control after 1 year of a DAIR procedure in the case of an early postoperative infection either after primary arthroplasty or after PJI-related revision arthroplasty. Materials and methods: All patients treated with a DAIR procedure within 3 months after onset of PJI between 2009 and 2017 were retrospectively included. Data were collected on patient and infection characteristics. All infections were confirmed by applying the Musculoskeletal Infection Society (MSIS) 2014 criteria. The primary outcome was successful control of infection at 1 year after a DAIR procedure, which was defined as the absence of clinical signs, such as pain, swelling, and erythema; radiological signs, such as protheses loosening; or laboratory signs, such as C-reactive protein (CRP) (<10) with no use of antibiotic therapy. Results: Sixty-seven patients were treated with a DAIR procedure (41 hips and 26 knees). Successful infection control rates of a DAIR procedure after primary arthroplasty (n=51) and after prior PJI-related revision arthroplasty (n=16) were 69 % and 56 %, respectively (p=0.38). The successful infection control rates of a DAIR procedure after an early acute infection (n=35) and after a hematogenous infection (n=16) following primary arthroplasty were both 69 % (p=1.00). Conclusion: In this limited study population, no statistically significant difference is found in infection control after 1 year between DAIR procedures after primary arthroplasty and PJI-related revision arthroplasty.


2018 ◽  
Vol 56 (9) ◽  
Author(s):  
Morgan I. Ivy ◽  
Matthew J. Thoendel ◽  
Patricio R. Jeraldo ◽  
Kerryl E. Greenwood-Quaintance ◽  
Arlen D. Hanssen ◽  
...  

ABSTRACTMetagenomic shotgun sequencing has the potential to transform how serious infections are diagnosed by offering universal, culture-free pathogen detection. This may be especially advantageous for microbial diagnosis of prosthetic joint infection (PJI) by synovial fluid analysis since synovial fluid cultures are not universally positive and since synovial fluid is easily obtained preoperatively. We applied a metagenomics-based approach to synovial fluid in an attempt to detect microorganisms in 168 failed total knee arthroplasties. Genus- and species-level analyses of metagenomic sequencing yielded the known pathogen in 74 (90%) and 68 (83%) of the 82 culture-positive PJIs analyzed, respectively, with testing of two (2%) and three (4%) samples, respectively, yielding additional pathogens not detected by culture. For the 25 culture-negative PJIs tested, genus- and species-level analyses yielded 19 (76%) and 21 (84%) samples with insignificant findings, respectively, and 6 (24%) and 4 (16%) with potential pathogens detected, respectively. Genus- and species-level analyses of the 60 culture-negative aseptic failure cases yielded 53 (88%) and 56 (93%) cases with insignificant findings and 7 (12%) and 4 (7%) with potential clinically significant organisms detected, respectively. There was one case of aseptic failure with synovial fluid culture growth; metagenomic analysis showed insignificant findings, suggesting possible synovial fluid culture contamination. Metagenomic shotgun sequencing can detect pathogens involved in PJI when applied to synovial fluid and may be particularly useful for culture-negative cases.


2020 ◽  
Vol 4 (04) ◽  
pp. 187-192
Author(s):  
Jared A. Warren ◽  
Oliver Scotting ◽  
Hiba K. Anis ◽  
James Bircher ◽  
Alison K. Klika ◽  
...  

AbstractDiagnostic thresholds used to standardize the definition for prosthetic joint infection (PJI) have largely focused on total joint arthroplasty (TJA). Established PJI thresholds exist for serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in TJA; however, they do not exist for revision hip hemiarthroplasty (rHHA). The purpose of this study was to establish thresholds for (1) ESR and (2) CRP to diagnose PJI in rHHA. Data were collected on a prospective cohort of 69 rHHA patients undergoing orthopaedic surgery between 1/2017 and 2/2019 in a single health care system. Procedures were categorized as septic or aseptic revisions using Musculoskeletal Infection Society (MSIS) criteria (2013). There were 44 ESRs (n = 28 aseptic, n = 16 septic) and 46 CRPs (n = 29 aseptic, n = 17 septic) available for analysis. Two tailed t-tests were performed to compare the mean ESR and CRP in aseptic and septic cases. Receiver operator characteristic (ROC) curves were generated to obtain diagnostic cutoff thresholds using the Youden's Index (J) for ESR and CRP. The mean ESR was 50.3 ± 30.6 mm/h versus 15.4 ± 17.7 mm/h (p < 0.001), while the mean CRP was 29.9 ± 24.8 mg/L versus 4.1 ± 8.2 mg/L (p < 0.001) for septic and aseptic revisions, respectively. The diagnostic threshold for PJI determined by the ROC curve was 44 mm/h for ESR (sensitivity = 56.3%; specificity = 100.0%; J = 0.563; area under the curve (AUC) = 0.845), while it was 12.5 mg/L for CRP (sensitivity = 70.6%; specificity = 96.6%; J = 0.672; AUC = 0.896). For patients with HHA, an ESR of 44 mm/h was and a CRP of 12.5 mg/L was highly specific for PJI. The thresholds are similar to the MSIS thresholds currently published. Larger prospective trials are needed to establish more robust and conclusive diagnostic criteria for PJI in HHA, including investigations not only of ESR and CRP but synovial white blood cell count and synovial polymorphonuclear leukocytes % as well.


2019 ◽  
Vol 101-B (8) ◽  
pp. 970-977 ◽  
Author(s):  
S. Kleiss ◽  
N. M. Jandl ◽  
A. Novo de Oliveira ◽  
W. Rüther ◽  
A. Niemeier

Aims The aim of this study was to evaluate the diagnostic accuracy of the synovial alpha-defensin enzyme-linked immunosorbent assay (ELISA) for the diagnosis of prosthetic joint infection (PJI) in the work-up prior to revision of total hip (THA) and knee arthroplasty (TKA). Patients and Methods Inclusion criteria for this prospective cohort study were acute or chronic symptoms of the index joint without specific exclusion criteria. Synovial fluid aspirates of 202 patients were analyzed and semiquantitative laboratory alpha-defensin ELISA was performed. Final diagnosis of PJI was established by examination of samples obtained during revision surgery. Results Sensitivity and specificity of the alpha-defensin ELISA for PJI were 78.2% (95% confidence interval (CI) 66.7 to 88.5) and 96.6% (95% CI 93.0 to 99.3). Positive and negative predictive values were 89.6% (95% CI 80.6 to 97.8) and 92.2% (95% CI 87.5 to 96.1). The test remained false-negative in 22% of septic revisions, most of which were due to coagulase-negative staphylococci all occurring in either late-chronic or early-postoperative PJI. Conclusion The routine use of synovial fluid alpha-defensin laboratory ELISA in the preoperative evaluation of symptomatic THAs and TKAs is insufficient to accurately diagnose PJI. Particularly in cases involving low-virulence organisms, such as coagulase-negative staphylococci, there remains a need for tests with a higher sensitivity. Cite this article: Bone Joint J 2019;101-B:970–977.


2019 ◽  
Author(s):  
Alexander J. Trotter ◽  
Rachael Dean ◽  
Celia E. Whitehouse ◽  
Jarle Mikalsen ◽  
Claire Hill ◽  
...  

AbstractBackgroundMicrobiological diagnosis of prosthetic joint infection (PJI) relies on culture techniques that are slow and insensitive. Rapid tests are urgently required to improve patient management. Calprotectin is a neutrophil biomarker of inflammation that has been demonstrated to be effective for the diagnosis of PJI. A calprotectin based lateral flow test has been developed for the rapid detection of PJI using synovial fluid samples.MethodsA convenience series of 69 synovial fluid samples from patients at the Norfolk and Norwich University Hospitals (NNUH) were collected intraoperatively from 52 hip and 17 knee revision operations. Calprotectin levels were measured using a new commercially available lateral flow assay for PJI diagnosis (Lyfstone). For all samples, synovial fluid was pipetted onto the lateral flow device and the signal was read using a mobile phone app after 15 minutes incubation at room temperature.ResultsAccording to the Musculoskeletal Infection Society (MSIS) criteria, 24 patients were defined as PJI positive and the remaining 45 were negative. The overall accuracy of the lateral flow test against the MSIS criteria was 75%. The test had a sensitivity and specificity of 75% and 76% respectively with a positive predictive value (PPV) of 62% and a negative predictive value (NPV) of 85%. Discordant results were then reviewed by the clinical team using available patient data to develop an alternative gold standard for defining presence/absence of infection (MSIS+). Compared to MSIS+, the test showed an overall accuracy of 83%, sensitivity and specificity of 95% and 78% respectively, a PPV of 62% and an NPV of 98%. Test accuracy for hip revisions was 77% and for knee revisions was 100%.ConclusionsThis study demonstrates that the calprotectin lateral flow assay is an effective diagnostic test for PJI. Our data suggests that the test is likely to generate false positive results in patients with metallosis and gross osteolysis.


2020 ◽  
Vol 102-B (6_Supple_A) ◽  
pp. 145-150 ◽  
Author(s):  
Molly A. Hartzler ◽  
Katherine Li ◽  
Michael B. Geary ◽  
Susan Marie Odum ◽  
Bryan D. Springer

Aims Two-stage exchange arthroplasty is the most common definitive treatment for prosthetic joint infection (PJI) in the USA. Complications that occur during treatment are often not considered. The purpose of this study was to analyze complications in patients undergoing two-stage exchange for infected total knee arthroplasty (TKA) and determine when they occur. Methods We analyzed all patients that underwent two-stage exchange arthroplasty for treatment of PJI of the knee from January 2010 to December 2018 at a single institution. We categorized complications as medical versus surgical. The intervals for complications were divided into: interstage; early post-reimplantation (three months); and late post-reimplantation (three months to minimum one year). Minimum follow-up was one year. In total, 134 patients underwent a first stage of a two-stage exchange. There were 69 males and 65 females with an mean age at first stage surgery of 67 years (37 to 89). Success was based on the new Musculoskeletal Infection Society (MSIS) definition of success reporting. Results Overall, 70 (52%) patients experienced a complication during the planned two-stage treatment, 36 patients (27%) experienced a medical complication and 47 (41%) patients experienced a surgical complication. There was an 18% mortality rate (24/134) at a mean of 3.7 years (0.09 to 8.3). During the inter-stage period, 28% (37/134) of patients experienced a total of 50 complications at a median of 47 days (interquartile range (IQR) 18 to 139). Of these 50 complications, 22 were medical and 28 required surgery. During this inter-stage period, four patients died (3%) and an additional five patients (4%) failed to progress to the second stage. While 93% of patients (125/134) were reimplanted, only 56% (77/134) of the patients were successfully treated without antibiotic suppression (36%, 28/77) or with antibiotic suppression (19%, 15/77) at one year. Conclusion Reported rates of success of two stage exchanges for PJI have not traditionally considered complications in the definition of success. In our series, significant numbers of patients experienced complications, more often after reimplantation, highlighting the morbidity of this method of treatment. Cite this article: Bone Joint J 2020;102-B(6 Supple A):145–150.


2020 ◽  
Vol 9 (7) ◽  
pp. 440-449 ◽  
Author(s):  
Zida Huang ◽  
Wenbo Li ◽  
Gwo-Chin Lee ◽  
Xinyu Fang ◽  
Li Xing ◽  
...  

Aims The aim of this study was to evaluate the performance of metagenomic next-generation sequencing (mNGS) in detecting pathogens from synovial fluid of prosthetic joint infection (PJI) patients. Methods A group of 75 patients who underwent revision knee or hip arthroplasties were enrolled prospectively. Ten patients with primary arthroplasties were included as negative controls. Synovial fluid was collected for mNGS analysis. Optimal thresholds were determined to distinguish pathogens from background microbes. Synovial fluid, tissue, and sonicate fluid were obtained for culture. Results A total of 49 PJI and 21 noninfection patients were finally included. Of the 39 culture-positive PJI cases, mNGS results were positive in 37 patients (94.9%), and were consistent with culture results at the genus level in 32 patients (86.5%) and at the species level in 27 patients (73.0%). Metagenomic next-generation sequencing additionally identified 15 pathogens from five culture-positive and all ten culture-negative PJI cases, and even one pathogen from one noninfection patient, while yielding no positive findings in any primary arthroplasty. However, seven pathogens identified by culture were missed by mNGS. The sensitivity of mNGS for diagnosing PJI was 95.9%, which was significantly higher than that of comprehensive culture (79.6%; p = 0.014). The specificity is similar between mNGS and comprehensive culture (95.2% and 95.2%, respectively; p = 1.0). Conclusion Metagenomic next-generation sequencing can effectively identify pathogens from synovial fluid of PJI patients, and demonstrates high accuracy in diagnosing PJI. Cite this article: Bone Joint Res 2020;9(7):440–449.


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