Synovial Calprotectin is Superior to Synovial Leukocyte Count in Excluding Chronic Periprosthetic Joint Infections, a Retrospective Cohort Study.

BACKGROUND: Synovial calprotectin is a promising biomarker for diagnosing chronic periprosthetic joint infections (PJIs), but its diagnostic value has not been directly compared to synovial leukocyte count and polymorphonuclear neutrophils. This study aimed to: (1) evaluate and compare the diagnostic accuracy between these markers in patients undergoing revision arthroplasty for chronic PJI or aseptic reasons; and (2) determine the best rule-out and rule-in test for PJI. METHODS: Synovial fluid samples from patients undergoing revision arthroplasty in hip and knee joints were collected and analyzed. Patients diagnosed with an acute PJI, patients treated with antibiotics 2 weeks prior to revision surgery, and/or patients who had active inflammatory joint disease were excluded. Periprosthetic joint infections were diagnosed based on the presence of a sinus tract and/or positive intraoperative cultures according to the European Bone and Joint Infection Society microbiological criteria. RESULTS: A total of 137 patients were included, of whom 19 (14%) were diagnosed with a PJI. Overall, synovial calprotectin had the highest diagnostic accuracy of all studied markers (area under the curve 96%). Synovial calprotectin, with a cutoff of 50 mg/L, had the highest negative predictive value of 100%. However, PMNs (> 80%) combined with a leukocyte count (> 3,000 cells/µL) showed the highest positive predictive value of an infection (positive predictive value17). CONCLUSIONS: Synovial calprotectin is the most accurate biomarker for ruling out a chronic PJI, while the combination of synovial leukocyte count and PMN is most reliable for ruling in a chronic PJI.

Beyond The Skin: B Cells in Pemphigus Vulgaris, Tolerance and Treatment.

Pemphigus vulgaris is a rare autoimmune bullous disease characterized by blistering of the skin and mucosa owing to the presence of autoantibodies against the desmosome proteins desmoglein 3 and occasionally in conjunction with desmoglein 1. Fundamental research into the pathogenesis of PV has revolutionized its treatment and outcome with rituximab, a B-cell-depleting therapy. The critical contribution of B cells to the pathogenesis of pemphigus is well accepted. However, the exact pathomechanism, mechanisms of onset, disease course, and relapse remain unclear. In this narrative review, we provide an overview of the fundamental research progress that has unfolded over the past centuries to give rise to current and emerging therapies. Furthermore, we summarized the multifaceted roles of B cells in pemphigus vulgaris, including their development, maturation, and antibody activity. Finally, we explored how these various aspects of B-cell function contribute to disease pathogenesis and pave the way for innovative therapeutic interventions.

What Is the Most Effective Treatment for Periprosthetic Joint Infection After Total Joint Arthroplasty in Patients with Rheumatoid Arthritis?: A Systematic Review.

BACKGROUND: Rheumatoid arthritis (RA) is a risk factor for periprosthetic joint infection (PJI) after total joint arthroplasty (TJA). The purpose of this study was to perform a systematic review comparing the failure rates of debridement, antibiotics, and implant retention (DAIR), one-stage exchange arthroplasty/revision (OSR), and 2-stage exchange arthroplasty/revision (TSR) for RA patients with PJI and identify risk factors in the RA population associated with increased treatment failure rate. METHODS: PubMed, Ovid MEDLINE, and Ovid Embase databases were screened with the terms "rheumatoid arthritis," "total joint arthroplasty," "prosthetic joint infection," and "treatment for PJI" on August 29, 2021. Four hundred ninety-one studies were screened, of which 86 were evaluated. The primary outcome evaluated was failure of surgical treatment for PJI. RESULTS: Ten retrospective cohort studies were included after full-text screening, yielding 401 patients with RA. Additional demographic and PJI management data were obtained for 149 patients. Patients with RA who underwent TSR demonstrated a lower failure rate (26.8%) than both DAIR (60.1%) and OSR (39.2%) (χ2 = 37.463, p < 0.00001). Patients with RA who underwent DAIR had a 2.27 (95% CI, 1.66-3.10) times higher risk of experiencing treatment failure than those who underwent TSR. Among risk factors, there was a significant difference in the C-reactive protein of patients who did vs. did not experience treatment failure (p = 0.02). CONCLUSION: TSR has a higher rate of success in the management of PJI patients with RA compared with DAIR and OSR. The complete removal of the infected prosthesis and delayed reimplantation may lower the treatment failure rate. LEVEL OF EVIDENCE: Level III. See Instructions for Authors for a complete description of levels of evidence.

Genetic Determinants in MRSA Carriage and Their Association with Decolonization Outcome.

Methicillin-resistant Staphylococcus aureus (MRSA) colonization increases the risk of infection. Response to decolonization treatment is highly variable and determinants for successful decolonization or failure of eradication treatment are largely unknown. Insight into genetic predictors of eradication failure is potentially useful in clinical practice. The aim of this study was to explore genetic characteristics that are associated with MRSA decolonization failure. This cohort study was performed in a tertiary care hospital in the Netherlands. Patients with ≥ 1 positive MRSA culture from any site and with available whole -genome sequencing data of the MRSA isolate between 2017 and 2022 were included. Lineages, resistance, and virulence factors were stratified by MRSA decolonization outcome. In total, 56 patients were included: 12/56 (21%) with treatment failure and 44/56 (79%) with successful decolonization (with or without preceding treatment). A significant association was found between ciprofloxacin-resistant lineages and failure of eradication (OR 4.20, 95%CI 1.11-15.96, P = 0.04). Furthermore, livestock-associated MRSA and the major community-associated MRSA lineages ST6-t304 and ST8-t008 were associated with successful eradication treatment or spontaneous clearance. In conclusion, this explorative study showed a higher eradication failure rate in complicated MRSA carriers with ciprofloxacin-resistant MRSA lineages, which are predominantly healthcare-associated. Further studies are warranted to confirm the higher eradication failure risk of ciprofloxacin-resistant lineages, and identify the underlying mechanisms.

The global burden of fracture-related infection: can we do better?

Fracture-related infection is a major complication related to musculoskeletal injuries that not only has important clinical consequences, but also a substantial socioeconomic impact. Although fracture-related infection is one of the oldest disease entities known to mankind, it has only recently been defined and, therefore, its global burden is still largely unknown. In this Personal View, we describe the origin of the term fracture-related infection, present the available data on its global impact, and discuss important aspects regarding its prevention and management that could lead to improved outcomes in both high-resource and low-resource settings. We also highlight the need for health-care systems to be adequately compensated for the high cost of human resources (trained staff) and well-equipped facilities required to adequately care for these complex patients. Our aim is to increase awareness among clinicians and policy makers that fracture-related infection is a disease entity that deserves prioritisation in terms of research, with the goal to standardise treatment and improve patient outcomes on a global scale.

A fluorogenic micrococcal nuclease-based probe for fast detection and optical imaging of Staphylococcus aureus in prosthetic joint and fracture-related infections.

PURPOSE: Staphylococcus aureus is the most common and impactful multi-drug resistant pathogen implicated in (periprosthetic) joint infections (PJI) and fracture-related infections (FRI). Therefore, the present proof-of-principle study was aimed at the rapid detection of S. aureus in synovial fluids and biofilms on extracted osteosynthesis materials through bacteria-targeted fluorescence imaging with the 'smart-activatable' DNA-based AttoPolyT probe. This fluorogenic oligonucleotide probe yields large fluorescence increases upon cleavage by micrococcal nuclease, an enzyme secreted by S. aureus. METHODS: Synovial fluids from patients with suspected PJI and extracted osteosynthesis materials from trauma patients with suspected FRI were inspected for S. aureus nuclease activity with the AttoPolyT probe. Biofilms on osteosynthesis materials were imaged with the AttoPolyT probe and a vancomycin-IRDye800CW conjugate (vanco-800CW) specific for Gram-positive bacteria. RESULTS: 38 synovial fluid samples were collected and analyzed. Significantly higher fluorescence levels were measured for S. aureus-positive samples compared to, respectively, other Gram-positive bacterial pathogens (p < 0.0001), Gram-negative bacterial pathogens (p = 0.0038) and non-infected samples (p = 0.0030), allowing a diagnosis of S. aureus-associated PJI within 2 h. Importantly, S. aureus-associated biofilms on extracted osteosynthesis materials from patients with FRI were accurately imaged with the AttoPolyT probe, allowing their correct distinction from biofilms formed by other Gram-positive bacteria detected with vanco-800CW within 15 min. CONCLUSION: The present study highlights the potential clinical value of the AttoPolyT probe for fast and accurate detection of S. aureus infection in synovial fluids and biofilms on extracted osteosynthesis materials.

Positive Intraoperative Cultures in Cup Revisions of THA: What Happens to the Stem?

BACKGROUND: Positive intraoperative cultures (PICs) are encountered in some patients undergoing revision of the acetabular cup after a previous THA. It is unknown whether PIC of the cup indicates whether the stem is infected as well and what happens to the stem during follow-up. QUESTIONS/PURPOSES: (1) What proportion of patients undergoing THA who undergo cup revision have PICs? (2) What is the survival of the stem during follow-up in cup revisions with PICs versus that of those with negative cultures? (3) Does antibiotic treatment of PIC of the cup prevent revision THA during follow-up? METHODS: In this retrospective, comparative multicenter study, five surgeons at four centers performed 338 acetabular cup revisions between January 2015 and December 2017. After evaluating the data, we excluded one patient because of an incomplete dataset and 77 patients because fewer than three intraoperative cultures were obtained during surgery, leaving 260 patients for analysis. Follow-up was 2 years. Patients were stratified into three cohorts: no PIC, one PIC, and two or more PICs. RESULTS: The proportion of patients with one or more PIC was 15% (39 of 260). A total of 8% (21 of 260) had one and 7% (18 of 260) had two or more PICs. Stem survival was lower in patients with two or more PICs, but stem revision for periprosthetic joint infection was similar between groups. Two-year survival, which was defined as freedom from revision for any cause or infection, was 97% (95% confidence interval 95% to 99%) in the group without PICs, 100% (95% CI 95% to 100%) in the group with one PIC, and 86% (95% CI 68% to 100%; p = 0.08) in the group with two or more PICs. None of the patients in the no PIC and one PIC groups were treated with antibiotics. In the two or more PICs cohort, 12 of 18 patients were treated. The stem survived in one of 12 patients treated with antibiotics versus two of six patients who were not treated with antibiotics. CONCLUSION: When treated with antibiotics, more than two PICs isolated during cup revision surgery do not have a major impact on survival of the stem during follow-up. A larger cohort of patients with PICs during cup revision might confirm these findings. LEVEL OF EVIDENCE: Level III, therapeutic study.

Should We Use Rifampicin in Periprosthetic Joint Infections Caused by Staphylococci When the Implant Has Been Exchanged? A Multicenter Observational Cohort Study.

Background: Previous studies demonstrated the efficacy of a rifampicin-based regimen in the treatment of acute staphylococcal periprosthetic joint infections (PJIs) treated with surgical debridement. However, evidence is lacking to support the use of rifampicin in cases where the implant is exchanged during revision. Methods: We included all consecutive cases of staphylococcal PJIs treated from January 2013 to December 2018 with revision surgery in this international, retrospective, multicenter observational cohort study. PJI was defined according to the European Bone and Joint Infection Society diagnostic criteria. A relapse or reinfection during follow-up, the need for antibiotic suppressive therapy, the need for implant removal, and PJI-related death were defined as clinical failure. Cases without reimplantation or with follow-up <12 months were excluded. Results: A total of 375 cases were included in the final analysis, including 124 1-stage exchanges (33.1%) and 251 2-stage exchanges (66.9%). Of those, 101 cases failed (26.9%). There was no statistically significant difference in failure of patients receiving rifampicin (22.5%, 42/187) and those not receiving rifampicin (31.4%, 59/188; P = .051). A subanalysis of chronic PJIs treated by 2-stage exchange arthroplasty demonstrated a lower failure rate in cases treated with rifampicin (15%) compared with the no-rifampicin group (35.5%; P = .005). In this subgroup, the use of rifampicin and an antibiotic holiday of >2 weeks were independent predictors of clinical success (odds ratio [OR], 0.36; 95% CI, 0.15-0.88; and OR, 0.19; 95% CI, 0.04-0.90; respectively). Conclusions: Combination treatment with rifampicin increases treatment success in patients with chronic staphylococcal PJI treated with 2-stage exchange arthroplasty.

Is an isolated positive sonication fluid culture in revision arthroplasties clinically relevant?

OBJECTIVES: The aim of this study was to investigate the clinical relevance of an isolated positive sonication fluid culture (SFC) in patients who underwent revision surgery of a prosthetic joint. We hypothesized that cases with a positive SFC have a higher rate of infection during follow-up compared with controls with a negative SFC. METHODS: This retrospective multicentre observational study was performed within the European Study Group of Implant-Associated Infections. All patients who underwent revision surgery of a prosthetic joint between 2013 and 2019 and had a minimum follow-up of 1 year were included. Patients with positive tissue cultures or synovial fluid cultures were excluded from the study. RESULTS: A total of 95 cases (positive SFC) and 201 controls (negative SFC) were included. Infection during follow-up occurred in 12 of 95 cases (12.6%) versus 14 of 201 controls (7.0%) (p = 0.125). In all, 79.8% of cases were with treated with antibiotics (76/95). Of the non-treated cases, 89% (17/19) had a positive SFC with a low virulent microorganism. When solely analysing patients who were not treated with antibiotics, 16% of the cases (3/19) had an infection during follow-up versus 5% of the controls (9/173) (p = 0.08). DISCUSSION: Although not statistically significant, infections were almost twice as frequent in patients with an isolated positive SFC. These findings require further exploration in larger trials and to conclude about the potential benefit of antibiotic treatment in these cases.

Rifampicin in periprosthetic joint infections: where do we stand and where are we headed?

INTRODUCTION: A periprosthetic joint infection (PJI) is a major complication of arthroplasty. Treatment of PJI consists of surgical debridement with or without the exchange of the implant and long-term antimicrobial treatment. Rifampicin is regarded as one of the cornerstones of antimicrobial treatment for staphylococcal PJI, but the exact role of rifampicin for PJI in different clinical scenarios remains to be elucidated. AREAS COVERED: In this perspective article, an overview is provided of in vitro, in vivo and clinical studies that were the basis of the current guidelines and recommendations for rifampicin use in daily practice for PJI. Controversial issues on indication, dosing, timing, duration, and antibiotic drug interactions will be addressed. Finally, the most urgent clinical questions on rifampicin use that need answering in the nearby future will be formulated. EXPERT OPINION: Many inquiries remain concerning the exact indications and clinical use of rifampicin in PJI. Randomized controlled trials are needed to answer these questions.

Cultures in periprosthetic joint infections, the imperfect gold standard?

Culture-negative periprosthetic joint infections (PJI) are commonly described in the literature. By implementing a routine diagnostic workup and by optimizing tissue sampling and processing, the culture-negative rate can easily be reduced. When faced with a culture-negative PJI, several serological and molecular techniques are available that may aid in finding the causative microorganism. Clinical clues may guide the treating physician towards more atypical and rare microorganisms. A multidisciplinary team consisting of orthopaedic surgeons, microbiologists and infectious disease specialist are warranted in tailoring diagnostic testing and deciding on the surgical and antibiotic treatment approach.

Antimicrobial treatment of patients with a periprosthetic joint infection: basic principles.

The antibiotic treatment of periprosthetic joint infections (PJI) is complicated by the presence of biofilm produced by bacteria on the abiotic surface of the implant. Bacteria within the deeper layers of the biofilm become metabolically less active, resulting in antibiotic tolerance due to several mechanisms. This review describes the basic principles of antibiotic treatment in PJI in relation to the behavior of bacteria within the biofilm. The concept of biofilm-active antibiotics will be explained from an in vitro as well as in vivo perspective. Evidence from clinical studies on biofilm-active antibiotics in PJI will be highlighted, mainly focusing on the role of rifampicin for Gram-positive microorganisms and fluoroquinolones for Gram-negative microorganisms. The optimal treatment duration will be discussed as the timing of switching to oral antibiotic therapy.

First evaluation of a commercial multiplex PCR panel for rapid detection of pathogens associated with acute joint infections.

Background: prompt recognition and identification of the causative microorganism in acute septic arthritis of native and prosthetic joints is vital to increase the chances of successful treatment. The aim of this study was to independently assess the diagnostic accuracy of the multiplex BIOFIRE® Joint Infection (JI) Panel (investigational use only) in synovial fluid for rapid diagnosis. Methods: synovial fluid samples were collected at the University Medical Center Groningen from patients who had a clinical suspicion of a native septic arthritis, early acute (post-operative, within 3 months after arthroplasty) periprosthetic joint infection (PJI) or late acute (hematogenous, ≥ 3 months after arthroplasty) PJI. JI Panel results were compared to infection according to Musculoskeletal Infection Society criteria and culture-based methods as reference standard. Results: a total of 45 samples were analysed. The BIOFIRE JI Panel showed a high specificity (100 %, 95 % confidence interval (CI): 78-100) in all patient categories. Sensitivity was 83 % (95 % CI: 44-97) for patients with a clinical suspicion of native septic arthritis ( n = 12 ), 73 % (95 % CI: 48-89) for patients with a clinical suspicion of a late acute PJI ( n = 14 ), and 30 % (95 % CI: 11-60) for patients with a clinical suspicion of an early acute PJI ( n = 19 ). Conclusion: the results of this study indicate a clear clinical benefit of the BIOFIRE JI Panel in patients with a suspected native septic arthritis and late acute (hematogenous) PJI, but a low clinical benefit in patients with an early acute (post-operative) PJI due to the absence of certain relevant microorganisms, such as Staphylococcus epidermidis, from the panel.

Sonication of Vascular Grafts and Endografts to Diagnose Vascular Graft Infection: a Head-To-Head Comparison with Conventional Culture and Its Clinical Impact.

Vascular graft and endograft infection (VGEI) is a severe complication associated with high mortality and is often challenging to diagnose. For the definitive microbiological diagnosis, sonication of vascular grafts may increase the microbiological yield of these biofilm-associated infections. The objective of this study was to determine whether sonication of explanted vascular grafts and endografts results in a higher diagnostic accuracy than conventional culture methods and aids in clinical decision-making. A prospective diagnostic study was performed comparing conventional culture with sonication culture of explanted vascular grafts in patients treated for VGEI. Explanted (endo)grafts were cut in halves and were either subjected to sonication or conventional culture. Criteria based on the Management of Aortic Graft Infection Collaboration (MAGIC) case definition of VGEI were used for definitive diagnosis. The relevance of sonication cultures was assessed by expert opinion to determine the clinical impact on decision-making. Fifty-seven vascular (endo)graft samples from 36 patients (four reoperations; 40 episodes) treated for VGEI were included; 32 episodes were diagnosed with VGEI. Both methods showed a positive culture in 81% of the cases. However, sonication culture detected clinically relevant microorganisms that went unnoticed by conventional culturing in 9 out of 57 samples (16%, 8 episodes) and provided additional relevant information regarding growth densities in another 11 samples (19%, 10 episodes). Sonication of explanted vascular grafts and endografts improves the microbiological yield and aids in the clinical decision-making for patients with a suspected VGEI compared to conventional culture alone. IMPORTANCE Sonication culture of explanted vascular grafts was shown to be a noninferior method compared to conventional culturing in diagnosing vascular graft and endograft infection (VGEI). Moreover, sonication culture has probable additional value in microbiological characterization of VGEI by giving more detailed information on growth densities, especially when the conventional culture shows intermediate growth. In this prospective design, for the first time, a direct comparison is made between sonication culturing and conventional culturing in VGEI, while taking clinical interpretation into account. Therefore, this study is another step toward a more accurate microbiological diagnosis of VGEI, influencing clinical decision-making.

Added Value of Abnormal Lymph Nodes Detected with FDG-PET/CT in Suspected Vascular Graft Infection.

Vascular graft and endograft infections (VGEI) cause a serious morbidity and mortality burden. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging is frequently used in the diagnostic workup, but the additional value of abnormal (18F-FDG active and/or enlarged) locoregional lymph nodes is unknown. In this retrospective study, the additional diagnostic value of abnormal locoregional lymph nodes on 18F-FDG PET/CT imaging for VGEI was evaluated, including 54 patients with a culture-proven VGEI (defined according to the Management of Aortic Graft Infection [MAGIC] group classification) and 25 patients without VGEI. 18F-FDG PET/CT was qualitatively and quantitatively assessed for tracer uptake and pattern at the location of the vascular graft, and locoregional lymph node uptake and enlargement (>10 mm). 18F-FDG uptake intensity and pattern independently predicted the presence of VGEI by logistic regression (Χ2: 46.19, p < 0.001), with an OR of 7.38 (95% CI [1.65, 32.92], p = 0.009) and 18.32 (95% CI [3.95, 84.88], p < 0.001), respectively. Single visual assessment of abnormal locoregional lymph nodes predicted the presence of VGEI with a sensitivity of 35%, specificity of 96%, PPV of 95%, and NPV of 41%. The visual assessment of abnormal lymph nodes after qualitative assessment of 18F-FDG uptake intensity and pattern at the vascular graft location did not independently predict the presence of VGEI by logistic regression (Χ2: 3.60, p = 0.058; OR: 8.25, 95% CI [0.74, 63.37], p = 0.096). In conclusion, detection of abnormal locoregional lymph nodes on 18F-FDG PET/CT has a high specificity (96%) and PPV (95%) for VGEI. However, it did not add to currently used 18F-FDG PET/CT interpretation criteria.