European Bone And Joint Infection Society Research Articles

The concordance between preoperative synovial fluid culture and intraoperative tissue cultures in periprosthetic joint infection: a systematic review.

Background: this systematic review aims to evaluate the concordance between preoperative synovial fluid culture and intraoperative tissue cultures in patients with periprosthetic joint infection (PJI) undergoing total hip (THA) or knee arthroplasty (TKA) revision surgery. Methods: this review was conducted in accordance with the preferred reporting items for a systematic review and meta-analysis of diagnostic test accuracy studies (PRISMA-DTA) statement. Cochrane, Embase, PubMed, and Web of Science databases were searched to identify studies involving patients who had THA or TKA revision surgery for PJI and for whom preoperative synovial fluid culture and intraoperative tissue cultures were performed. Studies were only included if the diagnosis of PJI was based on the EBJIS (the European Bone and Joint Infection Society) or MSIS (Musculoskeletal Infection Society) criteria. Risk of bias was assessed using an amended version of Joanna Briggs Institute's (JBI) critical appraisal checklist for case series. Results: seven studies were included in this review comprising 1677 patients. All studies had a retrospective study design and five studies explored patients undergoing revision surgery of THA or TKA. Concordance rates varied between 52 % and 79 %, but different authors defined and calculated concordance differently. Six studies were judged as having an unclear to high risk of bias and one study as having a low risk of bias. Conclusions: the included studies showed a wide range of concordance rates between preoperative synovial fluid culture and intraoperative tissue cultures and the majority of studies had a high risk of bias. Higher-quality studies are warranted to obtain a more accurate estimate of this concordance rate. We recommend continuing the use of a system such as the EBJIS definition or MSIS criteria when diagnosing PJI.

Diagnosing periprosthetic joint infections : a comparison of infection definitions: EBJIS 2021, ICM 2018, and IDSA 2013.

AimsThis study evaluated the definitions developed by the European Bone and Joint Infection Society (EBJIS) 2021, the International Consensus Meeting (ICM) 2018, and the Infectious Diseases Society of America (IDSA) 2013, for the diagnosis of periprosthetic joint infection (PJI).MethodsIn this single-centre, retrospective analysis of prospectively collected data, patients with an indicated revision surgery after a total hip or knee arthroplasty were included between 2015 and 2020. A standardized diagnostic workup was performed, identifying the components of the EBJIS, ICM, and IDSA criteria in each patient.ResultsOf 206 included patients, 101 (49%) were diagnosed with PJI with the EBJIS definition. IDSA and ICM diagnosed 99 (48%) and 86 (42%) as infected, respectively. A total of 84 cases (41%) had an infection based on all three criteria. In 15 cases (n = 15/206; 7%), PJI was present when applying only the IDSA and EBJIS criteria. No infection was detected by one definition alone. Inconclusive diagnoses occurred more frequently with the ICM criteria (n = 30/206; 15%) compared to EBJIS (likely infections: n = 16/206; 8%) (p = 0.029). A better preoperative performance of the EBJIS definition was seen compared with the ICM and IDSA definitions (p < 0.001).ConclusionThe novel EBJIS definition identified all PJIs diagnosed by any other criteria. Use of the EBJIS definition significantly reduced the number of uncertain diagnoses, allowing easier clinical decision-making.Cite this article: Bone Joint Res 2022;11(9):608–618.

Periprosthetic joint infection: Comparison of automated multiplex-PCR Unyvero i60 ITI cartridge system with bacterial culture and real-time PCR.

In the past, various efforts have been made to investigate diagnostic tools for periprosthetic-joint-infection (PJI). It is little-known about the diagnostic utility of polymerase-chain-reaction (PCR) in this context, especially concerning the role of multiplex-PCR assays comparing with conventional tissue culture. Evaluation of an automated-multiplex-PCR cartridge system for patients with suspicion of PJI in comparison with conventional microbiological culture and 16S-rDNA-PCR. On suspicion of PJI synovial fluid specimen were taken preoperatively or periprosthetic tissue was collected intraoperatively. Microbiological analysis included conventional culture, 16S-rDNA-PCR and automated-multiplex-PCR (Unyvero-i60-ITI®). The European-Bone-and-Joint-Infection-Society (EBJIS) criteria were used for PJI diagnosis. Positive and negative percent agreement was calculated. Total percentage agreement and Cohen's kappa coefficient were calculated. Sensitivity, specificity and positive predictive value of conventional culture, 16S-rDNA-PCR and multiplex-PCR were calculated. Ten specimens of proved PJI were used as control group. Fifty specimen were suitable for culture. 14 (28%) were classified as PJI, 36 (72%) were aseptic. Coagulase-negative staphylococci was the most frequent detected pathogen. Concordance-rate between mPCR and culture results was 75.6% with a Cohen's kappa of 0.28. Concordance-rate between mPCR and 16S-rDNA was 82.9%, Cohen's kappa was 0.13. Concordance analysis between culture results and 16S-rDNA lead to a concordance-rate of 88.9%. Cohen's kappa was calculated with 0.6. With regard to the microbiological culture as reference, sensitivity of the mPCR was 0.33 and specificity was 0.91. Sensitivity and specificity of the 16S-rDNA-PCR was 0.55 and 0.97. The positive predictive value was 0.57 for the mPCR and 0.83 for the 16S-rDNA-PCR. Due to fair agreement between mPCR and conventional microbiological culture, the tested multiplex-PCR could be an additional instrument for the detection of PJI but is not superior over the conventional culture.

Synovial calprotectin is a reliable biomarker for periprosthetic joint infections in acute-phase inflammation — a prospective cohort study

PurposeDiagnosing periprosthetic joint infections (PJI) are challenging and may be hampered by the presence of other causes of local inflammation. Conventional synovial and serum markers are not reliable under these circumstances. Synovial calprotectin has been recently shown as a promising biomarker for PJI in total hip (THA) and total knee arthroplasty (TKA). The aim of this study is to investigate if calprotectin is reliable for PJI diagnosis in cases with accompanying inflammation due to recent surgery, dislocation or implant breakage in primary and revision TKA and THA.MethodsThirty-three patients were included in this prospective study between July 2019 and October 2021 (17 patients undergoing surgery < 9 months, 11 dislocations, five implant breakage, respectively). Synovial white blood cell count (WBC), percentage of polymorphonuclear neutrophils (PMC), serum C-reactive protein (CRP) and synovial calprotectin, using a lateral-flow-assay, were analysed. These parameters were tested against a modified European-Bone-and-Joint-Infection-Society (EBJIS) definition with adjusted thresholds to account for the local inflammation. Statistic quality criteria were calculated and compared using a binary classification test.ResultsSeventeen patients were classified as confirmed infections according to the modified EBJIS definition (13 THA and 4 TKA). The calprotectin assay yielded a sensitivity of 0.88 (0.64, 0.99), a specificity of 0.81 (0.54, 0.96), a positive predictive value (PPV) of 0.83 (0.59, 0.96) and a negative predictive value (NPV) of 0.87 (0.60, 0.98).ConclusionsEven in the presence of local inflammation due to other, non-infectious causes, calprotectin is a reliable diagnostic parameter for the detection of a PJI in primary and revision THA and TKA.

Prosthetic joint infection diagnosis applying the three-level European Bone and Joint Infection Society (EBJIS) approach

Sensitive and specific tests for the diagnosis of prosthetic joint infection (PJI) are lacking. The aim of this study was to report clinical and microbiological findings of consecutive patients diagnosed with PJI at the University Hospital of Perugia, Perugia, Italy, and to validate these diagnoses utilizing the European Bone and Joint Infection Society (EBJIS) three-level diagnostic approach from 2021. Patients with a PJI diagnosis were included in this study and examined retrospectively. Overall, 133 patients were diagnosed with PJI: mean age 72 years, 54.9% female, and 55.6% with more than one comorbidity. The most frequent involved joints were hip 47% and knee 42%. Aetiology was identified in 88/133 (66.2%): staphylococci resulted the most frequent microorganisms and over 80% (45/54) resulted rifampin susceptible. Applying the EBJIS approach, PJI diagnosis resulted: confirmed in 101 (75.9%), likely in 25 (18.8%), and unlikely in 7 (5.3%). Likely PJIs aetiology was Staphylococcus aureus 11/25, coagulase-negative staphylococci 8/25, Streptococcus agalactiae 3/25, viridans group streptococci 2/25, and Pseudomonas aeruginosa 1/25. No statistically significant differences were detected among the three diagnosis groups with regard to clinical characteristics with the exception of a higher number of confirmed PJIs occurring < 3 months after implantation. The logistic regression analysis did not disclose any independent predictor of confirmed PJIs. We recommend using all the diagnostic tests available to approach PJI diagnosis, and suggest caution before rejecting PJI diagnosis in the presence of highly virulent microorganisms from a single sample, in patients without sinus tract, and in those receiving antimicrobial at the time microbiologic samples are collected. Study approved by Umbrian Regional Ethical Committee, Perugia, Italy, Prot. N. 23,124/21/ON of 10.27.2021.

Diagnosis of Chronic Infection at Total Hip Arthroplasty Revision Is a Question of Definition.

Purpose Contradicting definitions of periprosthetic joint infection (PJI) are in use. Joint aspiration is performed before total hip arthroplasty (THA) revision. This study investigated the influence of PJI definition on PJI prevalence at THA revision. Test quality of prerevision aspiration was evaluated for the different PJI definitions. Methods 256 THA revisions were retrospectively classified to be infected or not infected. Classification was performed according to the 4 different definitions proposed by the Musculoskeletal Infection Society (MSIS), the Infectious Diseases Society of America (IDSA), the International Consensus Meeting (ICM), and the European Bone and Joint Infection Society (EBJIS). Only chronic PJIs were included. Results PJI prevalence at revision significantly correlated with the applied PJI definition (p = 0.01, Cramer's V = 0.093). PJI prevalence was 20.7% for the MSIS, 25.4% for the ICM, 28.1% for the IDSA, and 32.0% for the EBJIS definition. For synovial fluid white blood cell count, the best ROC-AUC for predicting PJI was 0.953 in combination with the MSIS definition. Conclusion PJI definition significantly influences the rate of diagnosed PJIs at THA revision. Synovial fluid white blood cell count is a reliable means to rule out PJI. In cases with a borderline high synovial white blood cell count before THA revision as the only sign of chronic PJI, an extended diagnostic work-up should be considered.

Variation of synovial fluid leucocyte cell count and polymorphonuclear percentage in patients with aseptic revision total knee arthroplasty.

AimsCurrent guidelines consider analyses of joint aspirates, including leucocyte cell count (LC) and polymorphonuclear percentage (PMN%) as a diagnostic mainstay of periprosthetic joint infection (PJI). It is unclear if these parameters are subject to a certain degree of variability over time. Therefore, the aim of this study was to evaluate the variation of LC and PMN% in patients with aseptic revision total knee arthroplasty (TKA).MethodsWe conducted a prospective, double-centre study of 40 patients with 40 knee joints. Patients underwent joint aspiration at two different time points with a maximum period of 120 days in between these interventions and without any events such as other joint aspirations or surgeries. The main indications for TKA revision surgery were aseptic implant loosening (n = 24) and joint instability (n = 11).ResultsOverall, 80 synovial fluid samples of 40 patients were analyzed. The average time period between the joint aspirations was 50 days (SD 32). There was a significantly higher percentage change in LC when compared to PMN% (44.1% (SD 28.6%) vs 27.3% (SD 23.7%); p = 0.003). When applying standard definition criteria, LC counts were found to skip back and forth between the two time points with exceeding the thresholds in up to 20% of cases, which was significantly more compared to PMN% for the European Bone and Joint Infection Society (EBJIS) criteria (p = 0.001), as well as for Musculoskeletal Infection Society (MSIS) (p = 0.029).ConclusionLC and PMN% are subject to considerable variation. According to its higher interindividual variance, LC evaluation might contribute to false-positive or false-negative results in PJI assessment. Single LC testing prior to TKA revision surgery seems to be insufficient to exclude PJI. On the basis of the obtained results, PMN% analyses overrule LC measurements with regard to a conclusive diagnostic algorithm.Cite this article: Bone Jt Open 2021;2(8):566–572.

Diagnostic accuracy of neutrophil counts in histopathological tissue analysis in periprosthetic joint infection using the ICM, IDSA, and EBJIS criteria.

AimsHistology is an established tool in diagnosing periprosthetic joint infections (PJIs). Different thresholds, using various infection definitions and histopathological criteria, have been described. This study determined the performance of different thresholds of polymorphonuclear neutrophils (≥ 5 PMN/HPF, ≥ 10 PMN/HPF, ≥ 23 PMN/10 HPF) , when using the European Bone and Joint Infection Society (EBJIS), Infectious Diseases Society of America (IDSA), and the International Consensus Meeting (ICM) 2018 criteria for PJI.MethodsA total of 119 patients undergoing revision total hip (rTHA) or knee arthroplasty (rTKA) were included. Permanent histology sections of periprosthetic tissue were evaluated under high power (400× magnification) and neutrophils were counted per HPF. The mean neutrophil count in ten HPFs was calculated (PMN/HPF). Based on receiver operating characteristic (ROC) curve analysis and the z-test, thresholds were compared.ResultsUsing the EBJIS criteria, a cut-off of ≥ five PMN/HPF showed a sensitivity of 93% (95% confidence interval (CI) 81 to 98) and specificity of 84% (95% CI 74 to 91). The optimal threshold when applying the IDSA and ICM criteria was ≥ ten PMN/HPF with sensitivities of 94% (95% CI 79 to 99) and 90% (95% CI 76 to 97), and specificities of 86% (95% CI 77 to 92) and 92% (95% CI 84 to 97), respectively. In rTKA, a better performance of histopathological analysis was observed in comparison with rTHA when using the IDSA criteria (p < 0.001).ConclusionWith high accuracy, histopathological analysis can be supported as a confirmatory criterion in diagnosing periprosthetic joint infections. A threshold of ≥ five PMN/HPF can be recommended to distinguish between septic and aseptic loosening, with an increased possibility of detecting more infections caused by low-virulence organisms. However, neutrophil counts between one and five should be considered suggestive of infection and interpreted carefully in conjunction with other diagnostic test methods.Cite this article: Bone Joint Res 2021;10(8):536–547.

The impact of sonication cultures when the diagnosis of prosthetic joint infection is inconclusive.

In the absence of a gold standard criterion for diagnosing prosthetic joint infections (PJI), sonication of the removed implant may provide superior microbiological identification to synovial fluid and peri-implant tissue cultures. The aim of this retrospective study was to assess the role of sonication culture compared to tissue cultures for diagnosing PJI, using different consensus and international guidelines for PJI definition. Data of 146 patients undergoing removal of hip or knee arthroplasties between 2010 and 2018 were retrospectively reviewed. The International Consensus Meeting (ICM-2018), Musculoskeletal Infection Society (MSIS), Infectious Diseases Society of America (IDSA), the European Bone and Joint Infection Society (EBJIS), and a modified clinical criterion, were used to compare the performance of microbiological tests. McNemar´s test and proportion comparison were employed to calculate p-value. Overall, 56% (82/146) were diagnosed with PJI using the clinical criteria. Out of these cases, 57% (47/82) tested positive on tissue culture and 93% (76/82) on sonication culture. Applying this clinical criterion, the sensitivity of sonication fluid and tissue cultures was 92.7% (95% CI: 87.1%- 98.3%) and 57.3% (95% CI: 46.6%-68.0%) (p<0.001), respectively. When both methods were combined for diagnosis (sonication and tissue cultures) sensitivity reached 96.3% (95% CI: 91.5%-100%). Sonication culture and the combination of sonication with tissue cultures, showed higher sensitivity rates than tissue cultures alone for all diagnostic criteria (ICM-18, MSIS, IDSA and EBJIS) applied. Conversely, tissue culture provided greater specificity than sonication culture for all the criteria assessed, except for the EBJIS criteria, in which sonication and tissue cultures specificity was 100% and 95.3% (95% CI: 87.8-100%), respectively (p = 0.024). In a context where diagnostic criteria available have shortcomings and tissue cultures remain the gold standard, sonication cultures can aid PJI diagnosis, especially when diagnostic criteria are inconclusive due to some important missing data (joint puncture, histology).

Leukocyte esterase test and alpha-defensin test have similar accuracy for the diagnosis of periprosthetic joint infection.

The diagnosis of periprosthetic joint infection (PJI) after total joint replacement remains challenging. Synovial biomarkers are recommended as the major diagnostic criteria for PJI. The purpose of this study was to test the accuracy of the alpha-defensin test and compare it with that of the leukocyte esterase (LE) test for the diagnosis of PJI. We obtained 130 hip or knee aspirates from May 2015 to September 2018. PJI was defined according to the European Bone and Joint Infection Society (EBJIS) criteria. Synovial fluid samples were tested with the alpha-defensin ELISA and a LE strip. For the LE strip test, besides using the traditional threshold 500 (equal to ++), we are also using an improved one, with 500 (equal to ++) serving as the threshold for the tests before centrifugation and both 250 and 500 indicating positive results after centrifugation. The receiver operating characteristic (ROC) curves, sensitivity, specificity, positive predictive value, negative predictive value, and Cohen's Kappa value were calculated for the LE and alpha-defensin tests. The area under the curve (AUC) of alpha-defensin, LE strip test with traditional, and improved interpretation strategy were 0.875, 0.854, and 0.877, respectively. The Cohen's Kappa value for the alpha-defensin tests was 0.826 with the traditional LE interpretation strategy and 0.875 with the improved strategy. The present study shows that the use of the LE strip to test synovial fluid yielded an accuracy similar to that of the alpha-defensin immunoassay for the diagnosis of PJI; this finding supports the 2018 ICM PJI definition, which considers positive alpha-defensin and LE test results to be equivalent.

The EBJIS definition of periprosthetic joint infection

AimsThe diagnosis of periprosthetic joint infection (PJI) can be difficult. All current diagnostic tests have problems with accuracy and interpretation of results. Many new tests have been proposed, but there is no consensus on the place of many of these in the diagnostic pathway. Previous attempts to develop a definition of PJI have not been universally accepted and there remains no reference standard definition.MethodsThis paper reports the outcome of a project developed by the European Bone and Joint Infection Society (EBJIS), and supported by the Musculoskeletal Infection Society (MSIS) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Implant-Associated Infections (ESGIAI). It comprised a comprehensive review of the literature, open discussion with Society members and conference delegates, and an expert panel assessment of the results to produce the final guidance.ResultsThis process evolved a three-level approach to the diagnostic continuum, resulting in a definition set and guidance, which has been fully endorsed by EBJIS, MSIS, and ESGIAI.ConclusionThe definition presents a novel three-level approach to diagnosis, based on the most robust evidence, which will be useful to clinicians in daily practice.Cite this article: Bone Joint J 2021;103-B(1):18–25.

Diagnosis of Late Periprosthetic Joint Infection. Which Diagnostic Algorithm to Choose?

Background. Nowadays, according to the foreign and native registers data, the number of patients with periprosthetic infection (PJI) tends to increase. The early PJI diagnostics allows to provide timely effective treatment. Several widely used PJI diagnostic algorithms PJI exist. The objective of the study is comparative analysis of diagnostic value, accuracy and specificity of contemporary diagnostic algorithms. Materials and methods. A post-hoc analysis of 242 patients undergoing revision arthroplasty in 2018, held at FSFI FCTOE, was carried out. According to the study design, 127 patients were included in this study. PJI was diagnosed according to three known algorithms: ICM (International Consensus Meeting 2018), WAIOT (The World Association against Infection in Orthopedics and Trauma), EBJIS (The European Bone and Joint Infection Society 2018). Diagnostic sensitivity, specificity and total accuracy of each algorithm was carried out. The evaluation of ICM diagnostic algorithm was made with 2 variants: “not convincing = no infection”, “not convincing = infection”. The presence of infection was confirmed by bacteriological examination of synovial fluid aspirate, intraoperative biopsy of materials and sonification of explanted components. Results. The highest value of common accuracy was achieved in ICM 2018 algorithm — “not convincing = infection” was 91.3%, with sensibility and specificity — 89.3% and 93.0% respectively. The best specificity was shown by the algorithms WAIOT and ICM (“not convincing = no infection) – 95.8%, with sensibility and common accuracy — 80.4% and 89.0% respectively. The sensibility and specificity of EBJIS algorithm was 87.5% and 84.5%, respectively, the common accuracy — 85.8%. Conclusion. All included in investigation diagnostic algorithms showed high specificity values in diagnostics of hip and knee PJI without significant differences. Patients with subclinical PJI and low virulent pathogens have the biggest difficulties in PJI diagnostics. It seems that the selection of analyzed algorithms doesn’t play an important role, however PJI diagnostics requires complex approach with the use of different clinical and laboratory values.

Good accuracy of the alpha-defensin lateral flow test for hip periprosthetic joint infection: A pilot study in a retrospective cohort of 52 patients.

BACKGROUNDThe alpha-defensin lateral flow (ADLF) test is a new diagnostic tool for periprosthetic joint infection (PJI). Test accuracy for combined cohorts of hip and knee PJI has been reported to be good.AIMTo assess the accuracy of the ADLF test for hip PJI, and to compare three different diagnostic criteria for PJI.METHODSA cohort of 52 patients was identified, with a painful or poorly functioning total hip- or hemi-arthroplasty, that underwent aspiration and a subsequent ADLF test. PJI was diagnosed with Musculoskeletal Infection Society (MSIS) criteria, and sensitivity, specificity, overall accuracy, positive predictive value and negative predictive value were calculated. Furthermore, test specifics were compared with the European Bone and Joint Infection Society (EBJIS) and 2018 International Consensus Meeting (ICM) criteria for PJI.RESULTSUsing MSIS criteria, sensitivity was 100% (CI: 54%-100%) and specificity was 89% (CI: 76%-96%). Six true positives and 5 false positives were found, including one case of metallosis. Using EBJIS criteria, more PJIs were found (11 vs 6), sensitivity was lower (71%, CI: 42%-92%) and specificity was higher (97%, CI: 86%-100%), with 4 false negatives and one false positive result. Using 2018 ICM criteria, sensitivity was 91% (62%-100%) and specificity 100% (91%-100%). The results in this cohort are comparable to previous studies.CONCLUSIONOverall test accuracy of the ADLF test was good in this cohort, with a sensitivity of 100% and specificity of 89%. Using different PJI definition criteria, sensitivity and specificity changed slightly but overall accuracy remained around 90%. Using the ADLF test in metallosis cases can result in false positive results and should be performed with caution.

Alpha Defensin: A Diagnostic Accuracy Depending on the Infection Definition Used

BackgroundThe purpose of this study was to evaluate the alpha defensin qualitative detection (ADLF) sensitivity and specificity as compared with 3 standard classifications in the diagnostic management of chronic prosthetic joint infections. Materials and methodsA multicenter cohort of 136 patients with a painful arthroplasty was classified into either infected or noninfected according to the Musculoskeletal Infection Society (MSIS) score, Infectious Diseases Society of America (IDSA) score, European Bone and Joint Infection Society (EBJIS) score. The sensitivity and specificity of the ADLF test were calculated for each score. Spearman’s correlations between all scores were then analyzed, and multiple logistic regression was applied to identify independent variables strongly connected to the prosthetic joint infection probability. ResultsThe EBJIS score was positive in 68 patients, IDSA score in 50 patients, MSIS score in 41 patients, and ADLF in 40 patients. The ADLF sensitivity was 87.8% compared with MSIS, 70% compared with IDSA, and 55.8% compared with EBJIS. The ADLF specificity was in the range of 94%-97%. A good correlation was observed between synovial fluid cultures and ADLF (r = 0.73). Low to excellent correlations were recorded between ADLF and the EBJIS (r = 0.58), IDSA (r = 0.68), and MSIS (r = 0.84) scores. The synovial fluid’s white blood cell count was proven to be the biological test that most influenced the probability of a positive culture (P value: .005). DiscussionThe ADLF sensitivity was variable, whereas its specificity was excellent. The EBJIS score results significantly differed from those obtained via cultures, which possibly explains the ADLF low sensitivity compared with that of the EBJIS score.

Sonication of retrieved implants improves sensitivity in the diagnosis of periprosthetic joint infection

BackgroundSonication is a valuable tool in the diagnosis of periprosthetic joint infections (PJI). However, conditions and definition criteria for PJI vary among studies. The aim of this study was to determine the diagnostic performance (i.e., specificity, sensitivity) of sonicate fluid culture (SFC) against periprosthetic tissue culture (PTC), when using European Bone and Joint Infection Society (EBJIS) criteria.MethodsFrom March 2017 to April 2018, 257 implants were submitted for sonication. PJI was defined according to the EBJIS criteria as well as according to the International Consensus Meeting criteria of 2018 (ICM 2018). Only cases with at least one corresponding tissue sample were included. Samples were cultured using traditional microbiological plating techniques. Sensitivity and specificity were determined using two-by-two contingency tables. McNemar’s test was used to compare proportions among paired samples. Subgroup analysis was performed dividing the cohort according to the site of PJI, previous antibiotic treatment, and time of manifestation. Prevalence of pathogens was determined for all patients as well as for specific subgroups.ResultsAmong the 257 cases, 145 and 112 were defined as PJI and aseptic failure, respectively. When using the EBJIS criteria, the sensitivity of SFC and PTC was 69.0 and 62.8%, respectively (p = .04). Meanwhile, the specificity was 90.2 and 92.9%, respectively (p = .65). When adopting ICM 2018 criteria, the sensitivity of SFC and PTC was 87.5 and 84.4% (p = .63) respectively, while the specificity was 85.1 and 92.5% (p = .05), respectively. The most commonly identified pathogens were coagulase-negative staphylococci (26% overall), while 31% of PJI were culture-negative and 9% polymicrobial.ConclusionsSFC exhibited significantly greater sensitivity versus PTC when using the EBJIS criteria. Nevertheless, the diagnosis of PJI remains a difficult challenge and different diagnostic tools are necessary to optimize the outcome.

New Methods in the Diagnosis of Prosthetic Joint Infection

A timely and accurate diagnosis of periprosthetic joint infection (PJI) is crucial to plan adequate treatment. Purpose of the study. To evaluate the performance of new diagnostic tests for the diagnosis of PJI. Material and Methods. The performance of novel biomarkers in synovial fluid (i.e. D-lactate and alfa-defensin), molecular test (i.e. PCR of synovial fluid and sonication fluid), new methods to dislodge biofilm from implant surface (i.e. MicroDTTect) and sonication of explanted prosthesis were investigated in patients with PJI and aseptic loosening of the prosthesis. Results. D-lactate showed better sensitivity for the diagnosis of PJI compared to leukocyte count (86% and 80%, respectively). The optimal D-lactate cut-off value was calculated at 1.26 mmol/l. The ADLF test showed sensitivity of 84%, 67% and to 54% depending on classification criteria used for the diagnosis of PJI (Musculoskeletal Infection Society (MSIS), The Infectious Diseases Society of America (IDSA) and proposed European Bone and Joint Infection Society (EBJIS) criteria, respectively). Using the proposed EBJIS definition criteria, the sensitivity of the leukocyte count was significantly higher than that of the ADLF test (86% compared with 54%; p0,001), particularly in chronic PJI (81% compared with 44%, respectively; p0,001). The sensitivity of synovial fluid PCR was 60% and herewith comparable with synovial fluid culture (52%, p = 0,239). The sensitivity and specificity of sonication fluid culture were 58% and 100%, which was comparable to sonication fluid PCR 51% and 94%, respectively. DTT-based method showed low sensitivity for diagnosis of PJI (40%) compared to sonication (80%, p0,01). Conclusion. Synovial fluid D-lactate demonstrated good analytical performance and diagnostic value for the diagnosis of PJI. In particular, the high sensitivity for diagnosing infection and rapid availability of the test result make synovial fluid D-lactate suitable as screening test, whereas ADLF had limited sensitivity (54%) but high specificity (95%) and it should therefore not be used for screening, but rather as a confirmatory test for PJI. Multiplex PCR of synovial fluid and sonication fluid has similar sensitivity and specificity compared to synovial fluid culture, having the advantage of rapid availability of results (within 5 hours) and fully automated process. With further improvement of its performance and inclusion of additional primers, multiplex PCR may complement conventional cultures, especially for rapid and accurate diagnosis of low-grade PJI. Culture of samples obtained by sonication of prostheses showed better sensitivity for the microbiologic diagnosis of prosthetic hip and knee infection compared to chemical based dislodgement such as MicroDTTect.

Diagnosis of peripheral bone and prosthetic joint infections: overview on the consensus documents by the EANM, EBJIS, and ESR (with ESCMID endorsement).

Peripheral bone infection (PBI) and prosthetic joint infection (PJI) are two different infectious conditions of the musculoskeletal system. They have in common to be quite challenging to be diagnosed and no clear diagnostic flowchart has been established. Thus, a conjoined initiative on these two topics has been initiated by the European Society of Radiology (ESR), the European Association of Nuclear Medicine (EANM), the European Bone and Joint Infection Society(EBJIS), and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). The purpose of this work is to provide an overview on the two consensus documents on PBI and PJI that originated by the conjoined work of the ESR, EANM, and EBJIS (with ESCMID endorsement). After literature search, a list of 18 statements for PBI and 25 statements for PJI were drafted in consensus on the most debated diagnostic challenges on these two topics, with emphasis on imaging. Overall, white blood cell scintigraphy and magnetic resonance imaging have individually demonstrated the highest diagnostic performance over other imaging modalities for the diagnosis of PBI and PJI. However, the choice of which advanced diagnostic modality to use first depends on several factors, such as the benefit for the patient, local experience of imaging specialists, costs, and availability. Since robust, comparative studies among most tests do not exist, the proposed flowcharts are based not only on existing literature but also on the opinion of multiple experts involved on these topics. • For peripheral bone infection and prosthetic joint infection, white blood cell and magnetic resonance imaging have individually demonstrated the highest diagnostic performance over other imaging modalities. • Two evidence- and expert-based diagnostic flowcharts involving variable combination of laboratory tests, biopsy methods, and radiological and nuclear medicine imaging modalities are proposed by a multi-society expert panel. • Clinical application of these flowcharts depends on several factors, such as the benefit for the patient, local experience, costs, and availability.

Performance of synovial fluid D-lactate for the diagnosis of periprosthetic joint infection: A prospective observational study

ObjectivesSynovial fluid leukocyte count is the current standard test for diagnosing periprosthetic joint infection (PJI). As D-lactate is almost exclusively produced by bacteria, it represents a useful biomarker for bacterial infection. We evaluated the performance of synovial fluid D-lactate for the diagnosis of PJI and compared it with the synovial fluid leukocyte count. MethodsConsecutive patients with joint aspiration of a prosthetic hip, knee or shoulder joint were prospectively included. PJI was diagnosed according to the working criteria of the European Bone and Joint Infection Society (EBJIS). The synovial fluid D-lactate was determined spectrophotometrically at 570 nm, synovial fluid leukocytes were counted by flow cytometry. The receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance of investigated parameters. ResultsOf 148 patients, 44 (30%) were diagnosed with PJI and 104 (70%) with aseptic failure. For diagnosis of PJI, the sensitivity of synovial fluid D-lactate (at cut-off 1.263 mmol/l) was 86.4% [95% CI, 75.0–95.5%] and the specificity was 80.8% [95% CI, 73.1–88.5%]. The AUCs of D-lactate concentration and leukocyte count were 90.3% [95% CI 85.7–95.0%] and 91.0% [95% CI 85.1–96.8%], respectively (p = 0.8). Virulence of the pathogen did not influence the D-lactate concentration (p = 0.123). The synovial fluid erythrocyte concentration correlated with D-lactate in patients with aseptic failure (ρ = 0.339, p <0.01). ConclusionSynovial fluid D-lactate showed similar performance to the leukocyte count for diagnosis of PJI. Advantages of D-lactate test are requirement of low synovial fluid volume, short turnaround time and low cost.

Is the Enzyme-linked Immunosorbent Assay More Accurate Than the Lateral Flow Alpha Defensin Test for Diagnosing Periprosthetic Joint Infection?

Alpha defensin was proposed as a new biomarker in synovial fluid for the diagnostic workup of failed joint prostheses. To our knowledge, no comparative study of the performance of the quantitative enzyme-linked immunosorbent assay (ELISA) and qualitative lateral flow alpha defensin test has been reported. (1) Using the proposed European Bone and Joint Infection Society (EBJIS) criteria for defining periprosthetic joint infection (PJI), is there a difference in the diagnostic accuracy of quantitative ELISA and qualitative lateral flow alpha defensin tests? (2) Is there a difference in the performance of the two alpha defensin tests when using three definition classification systems (Musculoskeletal Infection Society [MSIS], Infectious Diseases Society of America [IDSA], and proposed EBJIS)? In this retrospective study of samples collected earlier as part of a related longitudinal study, we included patients in whom aspiration of the prosthetic hip or knee was performed as routine investigation before every revision arthroplasty. Between October 2016 and April 2017, a total of 73 patients were eligible for inclusion. As a result of an insufficient fluid volume for analysis (< 5 mL), two patients were excluded. Among the 71 patients in the final analysis, 54 had a knee and 17 a hip arthroplasty. Using the proposed EBJIS criteria, PJI was diagnosed in 22 patients (31%) and aseptic failure in 49 (69%). The alpha defensin ELISA and lateral flow tests were performed in synovial fluid. Patients were classified as having PJI or aseptic failure using the MSIS, the IDSA, and the proposed EBJIS criteria. Sensitivity and specificity of ELISA and the lateral flow alpha defensin test were calculated. Based on receiver operating characteristic analysis, area under the curve values were compared. When measured against the proposed EBJIS criteria, the sensitivity of alpha defensin ELISA and the lateral flow test was low and not different from one another with the numbers available at 50% (95% confidence interval [CI], 31%-69%) and 46% (95% CI, 27%-65%; p = 0.857), respectively, whereas both methods showed high specificity (98% [95% CI, 88%-100%]; p = 1.000). For sensitivity, the highest values were seen when compared against the MSIS criteria (ELISA: 85% [95% CI, 56%-97%], lateral flow: 77% [95% CI]; p = 0.871), intermediate with IDSA criteria (ELISA: 73% [95% CI, 48%-89%], lateral flow: 67% [95% CI]; p = 0.867), and lowest with proposed EBJIS criteria (ELISA: 50% [95% CI, 31%-69%], lateral flow: 46% [95% CI]; p = 0.763). Specificity, however, was high regardless of the criteria used, where ELISA and lateral flow produced results that were not different (MSIS: 98% [95% CI, 90%-100%], IDSA: 98% [95% CI, 90%-100%], EBJIS: 98% [95% CI, 88%-100%]; p = 1.000). The area under the curve of alpha defensin ELISA and the lateral flow test was similar, regardless of the definition criteria used (EBJIS: p = 0.566; IDSA: p = 0.425; MSIS: p = 0.339). There is no difference between the quantitative and qualitative alpha defensin test for confirmation of PJI, irrespective of applied definition criteria. Having the advantage of providing results within 10 minutes without the need for a laboratory facility, the qualitative test may be of interest in the intraoperative setting, however, at a cost of higher test expense. Level I, diagnostic study.

The Preoperative Microbial Detection is No Prerequisite for the Indication of Septic Revision in Cases of Suspected Periprosthetic Joint Infection.

Aim of This Study Periprosthetic joint infections (PJIs) require a special antimicrobial regimen, fundamentally different from an aseptic treatment, making a correct preoperative diagnosis essential. However, a successful preoperative microbe detection is not always possible. We wanted to find out (1) if a preoperative microbe detection is a prerequisite before starting a septic revision in suspected PJIs or if the preoperative diagnosis can solely be based on (para)clinical signs (persistent CRP >1 mg/dl, early X-ray loosening signs in the first 5 years, leucocytes joint aspiration >1700/µl, conspicuous history, and clinical signs like redness, pain, hyperthermia, swelling, and loss of function); (2) if patients with and without preoperative microbe detection have a different outcome; and (3) if the microbial growth is the most important criterion of a multifactorial PJI definition. Methods We included all first-line two-stage hip (49) and knee (47) revisions, performed in our department from 06/2013 on, with an available 2-year follow-up. A PJI was defined as one of the following four criteria: fistula or purulence, Krenn Morawietz type 2 or 3, joint aspirate > 2000/μl leukocytes or >70% granulocytes, and microbial growth. This multifactorial PJI definition was based on the European Bone and Joint Infection Society (EBJIS). The standardized diagnostic algorithm is described in detail. Results (1) 24 hip and 16 knee cases were treated without preoperative microbe detection solely on the basis of a (para)clinical diagnosis (see above). In the hip 91.6% (22 of 24 cases) showed an intraoperative microbe detection. In the knee, in 68.7% (11 of 16 cases) a microbe was detected intraoperatively and in 93.7% (15 of 16) at least one secure PJI criterion could be confirmed intraoperatively. (2) No statistical significant (p .517) difference between patients with (n = 56, reinfection rate 8.9%) and without (n = 40, 15%) preoperative microbe detection was found in a 2-year follow-up. (3) Microbial growth remains the overall (pre- and intraoperatively) most important criterion (hip 95.9%; knee 89.3%), followed by Krenn Morawietz for the intraoperative diagnosis (hip 67.3%, knee 48.9%), and joint aspiration for the knee and fistula for the hip, respectively, as preoperative criteria. Conclusion High rates of intraoperatively fulfilled EBJIS PJI criteria show that a preoperative microbe detection is not necessary before intervening in suspected PJIs. The indication for a septic revision can solely be based on (para)clinical signs. The new established diagnostic algorithm based on a multifactorial PJI definition showed high precision in finding PJIs.