Diagnosis Of Prosthetic Joint Infection Research Articles

An update about molecular biology techniques to detect orthopaedic implant-related infections.

Despite different criteria to diagnose a prosthetic joint infection (PJI), aetiological diagnosis of the causing microorganism remains essential to guide treatment.Molecular-biology-based PJI diagnosis is progressing (faster, higher specificity) in different techniques, from the experimental laboratory into clinical use.Multiplex polymerase chain reaction techniques (custom-made or commercial) provide satisfactory results in clinical series of cases, with specificity close to 100% and sensitivity over 70–80%.Next-generation metagenomics may increase sensitivity while maintaining high specificity.Molecular biology techniques may represent, in the next five years, a significant transformation of the currently available microbiological diagnosis in PJI.Cite this article: EFORT Open Rev 2021;6:93-100. DOI: 10.1302/2058-5241.6.200118

Diagnostic algorithm in septic total knee arthroplasty failure – What is evidence-based?

Prosthetic joint infection (PJI) is among the most common differential diagnoses of total knee arthroplasty failure. It is a challenging complication, not least because of the difficulty of establishing the correct diagnosis. The fact that no single diagnostic parameter or test has been identified that can accurately rule in or out PJI has led to an evolution of similar but competing definitions of PJI on the grounds of an array of criteria. This development has had very positive effects on the scientific evaluation of various methods of PJI diagnostics and treatment because of an increased comparability. However, it can be challenging to stay abreast of the evidence these definitions are based on. Also, the definitions alone do not necessarily entail an algorithm to aid in evaluating the right criteria in a sound order to be able to use the definitions as a sensible tool. The aim of this overview is to state the most recent evidence on the diagnostic parameters included in the most established PJI definitions and to exhibit and compare the few algorithmic approaches published.Clinical symptoms of PJI are very rarely reported on in the literature, hence the evidence on their diagnostic value is poor. The only symptom that is part of the established PJI definitions is the presence of a fistula. Concerning serological markers, CRP and ESR are still the common denominator in the literature, most recently accompanied by D-Dimer as a potentially suitable marker that has been included in the most recent update of the International Consensus Meeting (ICM) criteria. Imaging plays a minor role in the diagnostic cascade because of inconsistent evidence, and no role whatsoever in the established definitions. The most important preoperative diagnostic measure is arthrocentesis and cultural and cytological analysis of the synovial fluid. The much acclaimed α-Defensin test has so far not been included in the established criteria due to inconsistent reports on its diagnostic accuracy, it is, however, in wide use and considered an optional diagnostic tool for inconclusive cases. The most diagnostic accuracy lies in the cultural and histological analysis of periprosthetic tissue biopsies, whether they are gathered in a small procedure or during arthroplasty revision.Published algorithmic approaches to PJI diagnosis are much rarer than the well-established definitions by various associations. With their PJI definition, the American Academy of Orthopedic Surgeons (AAOS) published a consensus based flowchart for PJI diagnosis. Another algorithm was proposed as part of the endeavor of the MSIS and the first consensus meeting, also based on a consensus among experts. There have been two more recent publications of flowcharts based on the current evidence, one introduced at our institution in 2013, one established in 2020 by the German Society for Arthroplasty (AE).

Utility of lavage in addition to native fluid collection during fluoroscopically guided joint aspiration in infection diagnosis.

Image-guided prosthetic joint aspirations have been criticized in the literature as having poor sensitivity and specificity. Native fluid is typically analyzed for the presence of infection. Joint lavage during fluoroscopically guided aspiration of prosthetic joints is not routinely performed, and the lavage aspirate is not typically analyzed unless native fluid could not be aspirated for culture. This study aims to determine if concordance of culture results from native fluid and an additional joint lavage sample improves sensitivity and specificity in the diagnosis of prosthetic joint infection by fluoroscopically guided joint aspiration. A retrospective review of the fluoroscopically guided joint aspirations at our institution between December 2007 and December 2009 was performed. Data collected from the electronic medical record included culture results for both native fluid and lavage aspirate, histopathology results, final clinical diagnosis, as well as clinical/surgical management. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratio for infection were calculated for the following culture analysis scenarios: native fluid alone; lavage aspirate alone; native fluid; and lavage aspirate. Five hundredsixty-three aspirations, mostly prosthetic joints, were identified in the reviewed time period, of which 397 were sent for both native fluid and lavage aspirate analysis. Concordance between positive culture results from native fluid and joint lavage aspirate markedly increased the likelihood ratio for infection from 23.8 to 138.7and improved specificity and PPV of fluoroscopically guided joint aspiration, with similar sensitivity and NPV to that of native fluid culture alone.

Isolation of clinically significant microorganisms from prosthetic joint tissue using BacT/ALERT paediatric blood culture bottles compared with solid culture media and enrichment broth

The diagnosis of prosthetic joint infections and isolation of causative microorganisms has been found to be challenging in microbiology laboratories due to low sensitivity of microbiological culture. The aim of this study was to compare the use of conventional culture methods with the use of both enrichment broth and BacT/ALERT paediatric blood culture bottles, for the diagnosis of prosthetic joint infections. A total of 121 specimens from 44 patients were processed using three methods of microbiological culture: solid media, enrichment broth and paediatric bottles. The paediatric bottle method had a significantly lower (p<0.0001) time to detection than the standard solid media method, and was significantly more sensitive than solid media when used independently (93.33%, CI 83.27-98.09, vs 60.00%, CI 45.43-73.33). The combination use of solid media with paediatric bottles was found to be superior to the conventional solid media method and combination use with enrichment broth.

An Alternative One-Stage Exchange Arthroplasty Technique: For the Chronic Infected Total Hip.

BackgroundThere are various algorithms for the treatment of prosthetic joint infections (PJI). Currently, a two-stage hip exchange is considered the “gold standard” of care for treatment of chronic hip PJIs. However, there has been recent debate whether a one- or two-stage exchange offers the correct treatment. One-stage exchange arthroplasty has particularly gained interest due to less morbidity, mortality, and functional impairment.MethodsIn a retrospective case series, the outcome of patients with chronic hip PJIs treated with our one-stage exchange arthroplasty was analyzed. Between January 2015 and January 2020, eight patients underwent a one-stage exchange hip arthroplasty by a single surgeon at a single institution for a chronically infected total hip arthroplasty (THA). Original diagnosis of PJI was made in accordance with the 2011 version of the Musculoskeletal Infection Society (MSIS) criteria. The femoral stem was cemented with antibiotic-impregnated cement, and the polyethylene acetabular liner was cemented directly onto the acetabular bone with antibiotic-impregnated cement.ResultsOf the eight patients, three were female and five were male with a mean age of 70.5 years (SD 11.2, range 53-87). Six patients (75%) had infection eradication with retention of a stable implant and no additional surgery at a mean follow-up of 35.7 months (range 17-50). One patient (12.5%) underwent closed reduction for a dislocated THA at one month; however, this patient remained infection-free at the most recent follow-up of 41 months. One patient (12.5%) who was the oldest patient (87 years) died 18 days postoperatively. Overall, all living patients (87.5%) retained their one-stage exchange THA. One patient (12.5%, CI 95% 0.3-52.7) required additional surgery in the form of a closed reduction and zero patients (0.0%, CI 95% 0.0-36.9) required additional open surgery. ConclusionSingle-stage exchange arthroplasty with an antibiotic-impregnated cemented femoral stem and antibiotic-impregnated cemented polyethylene acetabular liner may be a useful option for the treatment of chronic hip PJIs. Our case series provides evidence that infection eradication and function preservation are possible using our one-stage exchange arthroplasty technique in a chronically infected THA. However, a multi-center study with randomization is necessary to further validate our results.

Two-stage exchange Arthroplasty is a viable treatment for Periprosthetic joint infection in inflammatory diseases

BackgroundInflammatory diseases are chronic autoimmune systemic autoimmune diseases, which may increase the risk of prosthetic joint infection (PJI) after total joint arthroplasty (TJA). However, to our best knowledge, few studies have studied the association between inflammatory diseases and subsequent failure after two-stage exchange reimplantation. The aims of this study were to identify the differences in (1) serum markers, synovial indicators and pathology results and (2) treatment outcomes following two-stage exchange arthroplasty between patients with or without inflammatory diseases.MethodsA retrospective review of 184 patients with PJI who underwent two-stage revision from 2014 to 2018 was conducted. PJI was diagnosed by using the MSIS criteria. Serum biomarkers, synovial fluid, organism and pathology results at the time of the PJI diagnosis and reimplantation were compared between patients with or without inflammatory diseases. Treatment success was defined according to the Delphi-based consensus criteria; Kaplan-Meier survivorship curves of the patients were generated and compared.ResultsThere was no difference in the biomarkers, pathology results or organism profile at the time of the PJI diagnosis. At reimplantation, the patients with inflammatory diseases generally had higher values of serum markers than those without inflammatory diseases. However, synovial white blood cell count was comparable in patients with inflammatory diseases (1142.8 ± 1385.3*109/mL) and group C (1315.8 ± 1849.3*109/mL, p = 0.841). The total treatment success rate was 91.3% (92% for individuals with inflammatory diseases and 91.2% for the controls). The survivorship of the inflammatory disease group was comparable with that of the control group.ConclusionTwo-stage exchange arthroplasty is a viable option for PJIs with inflammatory diseases. Synovial fluid analysis may be less affected by inflammatory diseases than serum markers did in the diagnosis persistent infection at reimplantation.

Image-guided in situ detection of bacterial biofilms in a human prosthetic knee infection model: a feasibility study for clinical diagnosis of prosthetic joint infections

PurposeDue to an increased human life expectancy, the need to replace arthritic or dysfunctional joints by prosthetics is higher than ever before. Prosthetic joints are unfortunately inherently susceptible to bacterial infection accompanied by biofilm formation. Accurate and rapid diagnosis is vital to increase therapeutic success. Yet, established diagnostic modalities cannot directly detect bacterial biofilms on prostheses. Therefore, the present study was aimed at investigating whether arthroscopic optical imaging can accurately detect bacterial biofilms on prosthetic joints.MethodsHere, we applied a conjugate of the antibiotic vancomycin and the near-infrared fluorophore IRDye800CW, in short vanco-800CW, in combination with arthroscopic optical imaging to target and visualize biofilms on infected prostheses.ResultsWe show in a human post-mortem prosthetic knee infection model that a staphylococcal biofilm is accurately detected in real time and distinguished from sterile sections in high resolution. In addition, we demonstrate that biofilms associated with the clinically most relevant bacterial species can be detected using vanco-800CW.ConclusionThe presented image-guided arthroscopic approach provides direct visual diagnostic information and facilitates immediate appropriate treatment selection.

Phenotypic Modulation of Biofilm Formation in a Staphylococcus epidermidis Orthopedic Clinical Isolate Grown Under Different Mechanical Stimuli: Contribution From a Combined Proteomic Study.

One of the major causes of prosthetic joint failure is infection. Recently, coagulase negative Staphylococcus epidermidis has been identified as an emergent, nosocomial pathogen involved in subclinical prosthetic joint infections (PJIs). The diagnosis of PJIs mediated by S. epidermidis is usually complex and difficult due to the absence of acute clinical signs derived from the host immune system response. Therefore, analysis of protein patterns in biofilm-producing S. epidermidis allows for the examination of the molecular basis of biofilm formation. Thus, in the present study, the proteome of a clinical isolate S. epidermidis was analyzed when cultured in its planktonic or sessile form to examine protein expression changes depending on culture conditions. After 24 h of culture, sessile bacteria exhibited increased gene expression for ribosomal activity and for production of proteins related to the initial attachment phase, involved in the capsular polysaccharide/adhesin, surface associated proteins and peptidoglycan biosynthesis. Likewise, planktonic S. epidermidis was able to aggregate after 24 h, synthesizing the accumulation associate protein and cell-wall molecules through the activation of the YycFG and ArlRS, two component regulatory pathways. Prolonged culture under vigorous agitation generated a stressful growing environment triggering aggregation in a biofilm-like matrix as a mechanism to survive harsh conditions. Further studies will be essential to support these findings in order to further delineate the complex mechanisms of biofilm formation of S. epidermidis and they could provide the groundwork for the development of new drugs against biofilm-related infections, as well as the identification of novel biomarkers of subclinical or chronic infections mediated by these emerging, low virulence pathogens.

Improved diagnosis of chronic hip and knee prosthetic joint infection using combined serum and synovial IL-6 tests.

AimsThis 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.MethodsPatients 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.ResultsA 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.ConclusionThe 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.

Advantages of 16S rRNA PCR for the diagnosis of prosthetic joint infection

16S ribosomal RNA (rRNA) PCR has been reported to be an effective diagnostic means in patients with prosthetic joint infection (PJI). The aim of the present meta-analysis is to establish the overall diagnostic accuracy of the measurement of 16S rRNA PCR for diagnosing PJI. PubMed, Web of Science, Cochrane Library, EMBASE and Wiley Online Library were searched for studies on 16S rRNA PCR in the diagnosis of PJI. The search incorporated all literature published up until December 2018 and the QUADAS-2 checklist were used for quality assessment. The sensitivity, specificity and other measures of accuracy of 16S rRNA PCR in the diagnosis of PJI were pooled. Statistical analysis was performed by employing Meta-Disc 1.4 and Stata 12.0 software. A total of 15 studies met the inclusion criteria. The summary estimates for 16S rRNA PCR in the diagnosis of PJI in these studies were pooled: Sensitivity, 0.70 (95% CI, 0.67-0.73); specificity, 0.93 (95% CI, 0.91-0.94); positive likelihood ratio, 10.93 (95% CI, 5.55-21.51); negative likelihood ratio, 0.33 (95% CI, 0.28-0.40); diagnostic odds ratio, 41.77 (95% CI, 19.90-87.68); and the area under the curve, 0.89. Subgroup analysis showed that the use of sonicate fluid and periprosthetic tissue has higher sensitivity (0.76; 95% CI, 0.69-0.82; and 0.73; 95% CI, 0.68-0.78, respectively), specificity (0.93, 95% CI, 0.90-0.96; and 0.95; 95% CI, 0.90-0.98, respectively) and area under the curve (0.93 and 0.98, respectively). 16S rRNA PCR assay plays an important role in the diagnosis of PJI. The results of 16S rRNA PCR assays should be interpreted in parallel with clinical findings, the results of microbiological, and other laboratory tests.

Shotgun-Metagenomics on Positive Blood Culture Bottles Inoculated With Prosthetic Joint Tissue: A Proof of Concept Study.

Clinical metagenomics is actively moving from research to clinical laboratories. It has the potential to change the microbial diagnosis of infectious diseases, especially when detection and identification of pathogens can be challenging, such as in prosthetic joint infection (PJI). The application of metagenomic sequencing to periprosthetic joint tissue (PJT) specimens is often challenged by low bacterial load in addition to high level of inhibitor and contaminant host DNA, limiting pathogen recovery. Shotgun-metagenomics (SMg) performed directly on positive blood culture bottles (BCBs) inoculated with PJT may be a convenient approach to overcome these obstacles. The aim was to test if it is possible to perform SMg on PJT inoculated into BCBs for pathogen identification in PJI diagnosis. Our study was conducted as a laboratory method development. For this purpose, spiked samples (positive controls), negative control and clinical tissue samples (positive BCBs) were included to get a comprehensive overview. We developed a method for preparation of bacterial DNA directly from PJT inoculated in BCBs. Samples were processed using MolYsis5 kit for removal of human DNA and DNA extracted with BiOstic kit. High DNA quantity/quality was obtained, and no inhibition was observed during the library preparation, allowing further sequencing process. DNA sequencing reads obtained from the BCBs, presented a low proportion of human reads (<1%) improving the sensitivity of bacterial detection. We detected a 19-fold increase in the number of reads mapping to human in a sample untreated with MolYsis5. Taxonomic classification of clinical samples identified a median of 96.08% (IQR, 93.85–97.07%; range 85.7–98.6%) bacterial reads. Shotgun-metagenomics results were consistent with the results from a conventional BCB culture method, validating our approach. Overall, we demonstrated a proof of concept that it is possible to perform SMg directly on BCBs inoculated with PJT, with potential of pathogen identification in PJI diagnosis. We consider this a first step in research efforts needed to face the challenges presented in PJI diagnoses.

Metagenomic next generation sequencing improves diagnosis of prosthetic joint infection by detecting the presence of bacteria in periprosthetic tissues

ObjectivesThe purpose of this study was to explore the role of mNGS in the diagnosis of PJI by detecting the presence of bacteria in periprosthetic tissues. MethodsPatients who were suspected of PJI and underwent surgery in our center were enrolled. Microbial culture and mNGS were performed on periprosthetic tissues collected intraoperatively. Patient age, body mass index (BMI), laboratory tests, microbial culture and mNGS results were recorded. The diagnostic performance of microbial culture and mNGS in the diagnosis of PJI was compared. ResultsA total of 44 patients were included. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of periprosthetic tissue microbial culture in the diagnosis of PJI were 72.72%, 77.27%, 76.19%, 73.91% and 75%, respectively. The sensitivity, specificity, PPV, NPV and accuracy of periprosthetic tissue mNGS in the diagnosis of PJI were 95.45%, 90.91%, 91.3%, 95.24% and 93.18%, respectively. The sensitivity and specificity of mNGS in the diagnosis of PJI were superior to those of microbial culture. ConclusionPeriprosthetic tissue can be used as an alternative to synovial fluid and sonication fluid, as mNGS can improve the diagnosis of PJI. mNGS of the periprosthetic tissues showed higher sensitivity than microbial culture.

Preliminary assessment of nanopore-based metagenomic sequencing for the diagnosis of prosthetic joint infection

ObjectivesPathogen identification is crucial for the diagnosis and management of periprosthetic joint infection (PJI). Although culturing methods are the foundation of pathogen detection in PJI, false-negative results often occur. Oxford nanopore sequencing (ONS) is a promising alternative for detecting pathogens and providing information on their antimicrobial resistance (AMR) profiles, without culturing. MethodsTo evaluate the capability of metagenomic ONS (mONS) in detecting pathogens from PJI samples, both metagenomic next-generation sequencing (mNGS) and mONS were performed in 15 osteoarticular samples from nine consecutive PJI patients according to the modified Musculoskeletal Infection Society (MSIS) criteria. The sequencing data generated from both platforms were then analyzed for pathogen identification and AMR detection using an in-house-developed bioinformatics pipeline. ResultsOur results showed that mONS could be applied to detect the causative pathogen and characterize its AMR features in fresh PJI samples. By real-time sequencing and analysis, pathogen identification and AMR detection from the initiation of sequencing were accelerated. ConclusionWe showed proof of concept that mONS can function as a rapid, accurate tool in PJI diagnostic microbiology. Despite efforts to reduce host DNA, the high proportion of host DNA was still a limitation of this method that prevented full genome analysis.

The routine use of synovial alpha-defensin is not necessary.

To establish the utility of adding the laboratory-based synovial alpha-defensin immunoassay to the traditional diagnostic work-up of a prosthetic joint infection (PJI). A group of four physicians evaluated 158 consecutive patients who were worked up for PJI, of which 94 underwent revision arthroplasty. Each physician reviewed the diagnostic data and decided on the presence of PJI according to the 2014 Musculoskeletal Infection Society (MSIS) criteria (yes, no, or undetermined). Their initial randomized review of the available data before or after surgery was blinded to each alpha-defensin result and a subsequent randomized review was conducted with each result. Multilevel logistic regression analysis assessed the effect of having the alpha-defensin result on the ability to diagnose PJI. Alpha-defensin was correlated to the number of synovial white blood cells (WBCs) and percentage of polymorphonuclear cells (%PMN). Intraobserver reliability and interobserver agreement did not change when the alpha-defensin result was available. Positive alpha-defensin results had greater synovial WBCs (mean 31,854 cells/μL, SD 32,594) and %PMN (mean 93.0%, SD 5.5%) than negative alpha-defensin results (mean 974 cells/μL, SD 3,988; p < 0.001 and mean 39.4% SD 28.6%; p < 0.001). Adding the alpha-defensin result did not alter the diagnosis of a PJI using preoperative (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.14 to 1.88; p = 0.315) or operative (OR 0.52, CI 0.18 to 1.55; p = 0.242) data when clinicians already decided that PJI was present or absent with traditionally available testing. However, when undetermined with traditional preoperative testing, alpha-defensin helped diagnose (OR 0.44, CI 0.30 to 0.64; p < 0.001) or rule out (OR 0.41, CI 0.17 to 0.98; p = 0.044) PJI. Of the 27 undecided cases with traditional testing, 24 (89%) benefited from the addition of alpha-defensin testing. The laboratory-based synovial alpha-defensin immunoassay did not help diagnose or rule out a PJI when added to routine serologies and synovial fluid analyses except in cases where the diagnosis of PJI was unclear. We recommend against the routine use of alpha-defensin and suggest using it only when traditional testing is indeterminate. Cite this article: Bone Joint J 2020;102-B(5):593-599.

Preliminary evaluation of a rapid lateral flow calprotectin test for the diagnosis of prosthetic joint infection.

AimsThis pilot study tested the performance of a rapid assay for diagnosing prosthetic joint infection (PJI), which measures synovial fluid calprotectin from total hip and knee revision patients.MethodsA convenience series of 69 synovial fluid samples from revision patients at the Norfolk and Norwich University Hospital were collected intraoperatively (52 hips, 17 knees) and frozen. Synovial fluid calprotectin was measured retrospectively using a new commercially available lateral flow assay for PJI diagnosis (Lyfstone AS) and compared to International Consensus Meeting (ICM) 2018 criteria and clinical case review (ICM-CR) gold standards.ResultsAccording to ICM, 24 patients were defined as PJI positive and the remaining 45 were negative. The overall accuracy of the lateral flow test compared to ICM was 75.36% (52/69, 95% CI 63.51% to 84.95%), sensitivity and specificity were 75.00% (18/24, 95% CI 53.29% to 90.23%) and 75.56% (34/45, 95% CI 60.46% to 87.12%), respectively, positive predictive value (PPV) was 62.07% (18/29, 95% CI 48.23% to 74.19%) and negative predictive value (NPV) was 85.00% (34/40, 95% CI 73.54% to 92.04%), and area under the receiver operating characteristic (ROC) curve (AUC) was 0.78 (95% CI 0.66 to 0.87). Patient data from discordant cases were reviewed by the clinical team to develop the ICM-CR gold standard. The lateral flow test performance improved significantly when compared to ICM-CR, with accuracy increasing to 82.61% (57/69, 95% CI 71.59% to 90.68%), sensitivity increasing to 94.74% (18/19, 95% CI 73.97% to 99.87%), NPV increasing to 97.50% (39/40, 95% CI 85.20% to 99.62%), and AUC increasing to 0.91 (95% CI 0.81 to 0.96). Test performance was better in knees (100.00% accurate (17/17, 95% CI 80.49% to 100.00%)) compared to hips (76.92% accurate (40/52, 95% CI 63.16% to 87.47%)).ConclusionThis study demonstrates that the calprotectin lateral flow assay could be an effective diagnostic test for PJI, however additional prospective studies testing fresh samples are required.Cite this article: Bone Joint Res. 2020;9(5):202–210.

Plasma d-Dimer Levels in Non-prosthetic Orthopaedic Implant Infection: Can it Aid Diagnosis?

d-Dimer estimation has been proposed as a reliable biomarker in prosthetic joint infections. Its role in non-prosthetic orthopaedic implant infections has, however, not been studied. The objectives of this study were to assess the levels of plasma d-Dimer in non-prosthetic orthopaedic implant infection. The diagnostic efficiency of d-dimer on orthopaedic implant-related infection was evaluated. The study was designed as a cross-sectional comparative study. Patients who presented with orthopaedic implant-related infection as diagnosed by modified MSIS criteria were allocated to case group (n = 49) and patients who underwent surgical procedures with orthopaedic implants with no evidence of infection at 6weeks postoperatively were allocated to the control group (n = 48). Serum d-Dimer levels were assessed quantitatively using immunoturbidimetric assays in both groups and compared between both groups. The mean (± SD) value of serum d-Dimer in case group was 0.64 (± 0.45) μg/ml and control group was 0.77 (± 0.47) μg/ml. No significant difference was found in serum d-Dimer levels between cases and control groups (p value = 0.183). The diagnostic accuracy of d-dimer in orthopaedic implant-related infection also could not be demonstrated. The findings of d-dimer as a marker for the diagnosis of prosthetic joint infections cannot be extrapolated to non-prosthetic orthopaedic implant infection.

Comparison of broad-range polymerase chain reaction and metagenomic next-generation sequencing for the diagnosis of prosthetic joint infection

PurposeThe aims of our study were to (1) evaluate the concordance of both methods for detecting prosthetic joint infection (PJI) pathogens in joint fluid and to (2) clarify whether broad-range polymerase chain reaction (BR-PCR) can be used as a verification method for metagenomic next-generation sequencing (mNGS) for PJI diagnosis. MethodsIn total, 63 patients underwent total joint arthroplasty, with 45 PJI and 18 aseptic failure patients included. Joint fluids were sampled after antibiotics were withheld for more than 2 weeks, and then, culture, BR-PCR and mNGS were performed for all samples. ResultsThe joint fluid BR-PCR sensitivity was 82.2%, which was not significantly different from that of mNGS (95.6%) or culture (77.8%). The specificities of the 3 methods were all 94.4%. BR-PCR failed to identify the pathogens in 1 polymicrobial infection patient and 4 fungal infection patients. ConclusionmNGS was more sensitive than BR-PCR for detecting PJI pathogens in joint fluid. BR-PCR is insufficient for use as an mNGS verification method.

Assessment of a Multiplex Serological Test for the Diagnosis of Prosthetic Joint Infection: a Prospective Multicentre Study.

Introduction: The diagnosis of prosthetic joint infections (PJIs) can be difficult in the chronic stage and is based on clinical and paraclinical evidence. A minimally invasive serological test against the main pathogens encountered during PJI would distinguish PJI from mechanical loosening.Methods: We performed a prospective, multicentre, cross-sectional study to assess the contribution of serology in the diagnosis of PJI. Over a 2-year period, all patients undergoing prosthesis revision were included in the study. A C-reactive protein assay and a serological test specifically designed against 5 bacterial species (Staphylococcus aureus, S. epidermidis, S. lugdunensis, Streptococcus agalactiae, Cutibacterium acnes) were performed preoperatively. Five samples per patient were taken intraoperatively during surgery. The diagnosis of PJI was based on clinical and bacteriological criteria according to guidelines.Results: Between November 2015 and November 2017, 115 patients were included, 49 for a chronic PJI and 66 for a mechanical problem. Among patients with PJI, a sinus tract was observed in 32.6% and a C-reactive protein level ≥10 mg/L in 74.5%. The PJI was monomicrobial in 43 cases (targeted staphylococci, 24; S. agalactiae, 1; C. acnes, 2; others, 16), and polymicrobial in 6 cases (12.2%). Sensitivity, specificity, positive predictive value and negative predictive value were 75.0%, 82.1%, 58.3% and 90.8%, respectively, for targeted staphylococci. Specificity/negative predictive value was 97.3%/100% for S. agalactiae and 83.8% /96.9% for C. acnes.Conclusions: The serological tests are insufficient to affirm the diagnosis of PJI for the targeted bacteria. Nevertheless, the excellent NPV may help clinicians to exclude PJI.

Serial C-reactive Protein Monitoring in Prosthetic Joint Infection: A Powerful Predictor or Potentially Pointless?

BackgroundSerum C-reactive protein (CRP) is an important test in the initial diagnosis of prosthetic joint infection (PJI). There is no widely accepted algorithm for the resolution of PJI. Surgeons have traditionally used CRP to determine if the infection has resolved. However, this practice is not currently supported by significant data. MethodsA retrospective analysis of our departmental arthroplasty database was conducted to determine mean values of CRP pre and postoperatively for PJI treated with the debridement, antibiotics and implant retention (DAIR) procedure, single-stage revision and two-stage revision. Receiver operating characteristic (ROC) curves were calculated to determine the sensitivity and specificity of CRP testing in diagnosing persistent infection.ResultsOf the 121 patients who had undergone treatment (75 hip replacements and 48 knee replacements), there were 26 cases of persistent infection. There was no statistical significance in the mean CRP values between successful and unsuccessful treatment groups. The areas under ROCs (AUCs) for CRP values predicting outcomes ranged from 0.46 to 0.73.ConclusionOur study does not support the use of serial CRP monitoring as an indicator of the successful eradication of PJI.

Patient-Related Factors Affecting the Sensitivity of Sonication of Removed Hip and Knee Implants Against Conventional Tissue Cultures for Diagnosis of Prosthetic Joint Infections

Despite its decreasing incidence, prosthesis-related infections remain a research, diagnostic, therapeutic and cost-related problem. Our study aim was to compare the diagnostic accuracy of conventional periprosthetic tissue culture and culture of sonication fluid of the explanted hardware and to investigate the role of patientrelated factors affecting the sensitivity of the sonication method. We investigated 70 patients undergoing revision hip or knee arthroplasty, at our institution. Patients’ medical history and demographic characteristics were recorded. We compared the culture of samples obtained by sonication of explanted hip and knee prostheses with conventional culture of periprosthetic tissue for the microbiological diagnosis of prosthetic-joint infection. Thirty-two patients had septic loosening and 38 aseptic loosening (48 hip prostheses and 22 knee prostheses). The sensitivities of sonication fluid culture and conventional tissue cultures were 81.25% and 56.25%, respectively (p-value = 0.043). The sensitivity of the sonication method was statistically higher in obese, diabetic patients, with age above 60, in uncemented arthroplasties and in arthroplasties because of primary osteoarthritis (p-values &lt; 0.05). The sonication method has a greater sensitivity than the conventional periprosthetic tissue cultures for the periprosthetic infections, especially in obese, diabetic patients, with age above 60, in uncemented arthroplasties and in arthroplasties because of primary osteoarthritis.