Review of recent advances in the diagnosis and management of periprosthetic joint infection after total knee arthroplasty part 2: single-stage or two-stage surgical technique?

Periprosthetic joint infection (PJI) after total knee arthroplasty is a complication that affects approximately 2-3% of patients. The management of this issue is complicated and expensive for both the patients and the healthcare system. Multiple management options are available including antibiotic suppressive therapy, surgical management, and salvage procedures. Surgical management is considered a popular option for treating PJI, with multiple available surgical techniques, including single-stage revision arthroplasty and two-stage revision arthroplasty among others. Two-stage revision has been considered the gold standard for treating PJI. This method consists of two surgical procedures with a time interval in between, the first procedure aims to eradicate the infection along with implanting either a static or a mobile spacer, while the second intervention aims to remove the spacer and implant a new prothesis. During the interval period the patient is closely monitored through a handful of laboratory tests and clinical signs that help in assessing the optimal time of undertaking the second stage. However, in recent years, the single-stage method has gained much attention for its comparable outcomes and fewer complications. Contrary to the two-stage method, the single-stage approach consists only of one procedure in which the old infected prosthesis is removed and a new one is implanted. Many articles have compared the two methods over the years but have not agreed on a particular approach to be more potent in eliminating infection and providing better outcomes. Plenty of questions are yet to be answered regarding the two methods, including the superior type of spacer, interim period duration, and single-stage revision inclusion criteria. We herein, aim to address these issues, highlighting recent advances in managing this morbid complication and discussing controversial topics in the staged procedures.

Homograft implant for prosthetic aortic endocarditis with paravalvular abscess in a patient with persistent left superior vena cava.

We present a case report detailing the surgical intervention in a patient with prosthetic aortic valve endocarditis complicated by a paravalvular abscess extending to the mitral-aortic fibrosa. Urgent surgery was required due to severe detachment of the prosthetic aortic valve, marking her third cardiac surgical procedure. Notably, preoperative imaging revealed the presence of a persistent left superior vena cava, a rare vascular anomaly requiring specialized cannulation techniques. The surgical approach involved removal of the infected tissue and prosthetic valve, followed by replacement with a cryopreserved aortic homograft, chosen for its anatomical adaptability.

[Epidermal inclusion cyst mimicking an implantable cardiac defibrillator pocket infection: a rare finding]. / Non sempre si tratta di infezioni: un raro caso di cisti di inclusione epidermoide a livello della tasca di un defibrillatore impiantabile simulante un decubito tardivo.

We report an unusual case of an elderly man presenting with formation and rupture of an epidermal inclusion cyst at the level of an implantable cardiac defibrillator (ICD) pocket. The lesion appeared 2 years after ICD implantation, mimicking a decubitus or a pocket infection. Surgical revision showed no signs of infection of the pocket, but the pedunculated lesion was rooted in the subcutaneous tissue, whit an implant base external to the ICD pocket, which was removed and analyzed histologically, confirming the diagnosis of epidermal inclusion cyst. The pathophysiological mechanism of cyst formation is discussed. This case highlights the importance of an increased attention to lesions that mimic infections of a cardiac implantable electronic device pocket, thus preventing unnecessary complete removal of the device system.

An Approach to Cardiac Implantable Electronic Device Pocket Infections: From Prevention to Diagnosis and Management.

Cardiac implantable electronic device (CIED) infections are a highly morbid and potentially fatal complication of CIED implantation. Prompt diagnosis is paramount to the proper management of such infections. This review seeks to highlight the pathophysiology, risk factors, diagnostic approach, and prevention strategies for CIED infection, with an emphasis on pocket infection. Management will be discussed in detail, with complete device removal representing the standard of case, but with conservative management representing a potential alternative for patients at high risk for extraction. The high prevalence of CIED in the cardiac population renders understanding of this subject essential for the practicing clinician.

Clinical evaluation of a multiplex PCR-based test for joint infection: a prospective diagnostic accuracy study of forty-nine patients.

PURPOSE: The purpose of this study was to evaluate the diagnostic accuracy (sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV)) of the PCR-based BioFire® Joint Infection Panel (BJI Panel) against microbiological culture growth for patients suspected of having a native or prosthetic joint infection. METHODS: Synovial fluid and tissue biopsies were prospectively collected from patients from June 2022 to June 2023. The results of the BJI Panel were compared with those of culture growth. RESULTS: 51 samples were included. Including all pathogens, the sensitivity was 69%, the specificity 89%, the PPV 73% and the NPV 86%. Including only pathogens in the BJI Panel, the sensitivity was 100%, the specificity 90%, the PPV 73% and the NPV 100%. CONCLUSION: The BJI Panel has a high accuracy for detecting the pathogens in its panel, but the absence of important common pathogens from the panel reduces its sensitivity and NPV. With a short turnaround time and precise pathogen detection, the BJI Panel has the potential to add value as a complementary diagnostic method.

Construction and evaluation of a combined diagnostic model for chronic periprosthetic joint infection based on serological tests.

BACKGROUND: Early diagnosis of chronic periprosthetic joint infection (CPJI) is crucial for ensuring effective treatment and improving patient outcomes. However, many auxiliary diagnostic tests are challenging to implement on a large scale due to economic and technical constraints, making CPJI diagnosis difficult. This study aims to design and validate a combined diagnostic model based on commonly used serological tests to evaluate its diagnostic value for CPJI and develop a diagnostic nomogram. METHODS: A retrospective study from January 2019 to February 2024 involving 170 patients undergoing knee and hip arthroplasty revision for CPJI and aseptic loosening (AL) was conducted across two medical centers. These patients were divided into the training set and validation set. Patients were categorized into CPJI and AL groups based on infection status. Serological tests conducted upon admission were collected, and single-factor and multi-factor logistic regression analyses were used to identify independent diagnostic factors for early infection. These factors were integrated to construct a nomogram model. The model's performance was evaluated using the receiver operating characteristic area under the curve (AUC), Hosmer-Lemeshow test, decision curve analysis (DCA), and calibration curve, with external validation conducted on the validation set. RESULTS: Multivariate logistic regression analysis showed that C-reactive protein (CRP), procalcitonin (PCT), and Platelet count/mean platelet volume ratio (PVR) were independent diagnostic factors for CPJI (p < 0.05). The AUCs for diagnosing CPJI using these individual factors were 0.806, 0.616, and 0.700 (p < 0.05), respectively, while their combined detection achieved an AUC of 0.861 (p < 0.05). The DCA clinical impact curve shows the combined model has good clinical utility when the threshold probability of infection presence is between 0.16 and 0.95. Similar results were obtained in the external validation cohort, with the combined detection having an AUC of 0.893. CONCLUSION: The combined diagnostic model of CRP, PCT, and PVR significantly improves the The combined diagnostic model of CRP, PCT, and PVR significantly improves the diagnostic performance for CPJI compared to individual serum biomarkers. It exhibits good sensitivity, specificity, and clinical applicability, providing valuable references for CPJI diagnosis.

Application of a metatranscriptomics technology, CSI-Dx, for the detection of pathogens associated with prosthetic joint infections.

Preoperative identification of causal organism(s) is crucial for effective prosthetic joint infection treatment. Herein, we explore the clinical application of a novel metatranscriptomic (MT) workflow, CSI-Dx, to detect pathogens associated with prosthetic joint infection. MT provides insight into transcriptionally active microbes, overcoming limitations of culture-based and available molecular methods. This study included 340 human synovial fluid specimens subjected to CSI-Dx and traditional culture-based methods. Exploratory analyses were conducted to determine sensitivity and specificity of CSI-Dx for detecting clinically-relevant taxa. Our findings provide insights into the active microbial community composition of synovial fluid from arthroplasty patients and demonstrate the potential clinical utility of CSI-Dx for aiding prosthetic joint infection diagnosis. This approach offers potential for improved sensitivity and acceptable specificity compared to synovial fluid culture, enabling detection of culturable and non-culturable microorganisms. Furthermore, CSI-Dx provides valuable information on antimicrobial resistance gene expression. While further optimization is needed, integrating metatranscriptomic technologies like CSI-Dx into routine clinical practice can revolutionize prosthetic joint infection diagnosis by offering a comprehensive and active snapshot of associated pathogens.

New diagnostic techniques for diagnosing facture-related infections.

The diagnosis of fracture-related infections (FRI) is challenging and requires interdisciplinary efforts. Many diagnostic approaches are based on the algorithms established for prosthetic joint infections (PJI). Data specific to FRI are limited. Microbiological diagnostics include tissue culture, sonication, and molecular methods. Novel metagenomic analyses are increasingly being used in clinical diagnostic practice. In addition to bacterial detection, the study of host tissue factors has the potential to transform the diagnostics of FRI by facilitating the assesment of clinical significance in clinical samples. The integration of host tissue analysis into microbiology reports has great potential to improve the diagnosis of FRI. This mini-review describes the potential improvement of diagnostic techniques by integrating new approaches into the diagnostic algorithm of fracture-related infections.

Feasibility of mNGS in joint replacement patients exhibiting elevated ESR and CRP levels without an underlying diagnosis.

OBJECTIVE: The aim of this study is to investigate the viability of performing initial artificial joint replacement surgery in patients presenting with unexplained elevations in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels. METHODS: A cohort of 22 patients, comprising 11 cases each for knee and hip joint replacements, who underwent initial artificial joint replacement surgery between November 2020 and January 2022, was recruited. All patients exhibited elevated levels of ESR and CRP prior to surgery, the etiology of which remained undetermined. Intraoperatively, joint effusion and periarticular tissues were preserved for subsequent bacterial culture and metagenomic next-generation sequencing (mNGS). Postoperatively, a combination of intravenous and local antibiotics was administered for anti-infective management. In cases where bacterial culture and/or mNGS yielded positive results, patients were diagnosed with periprosthetic joint infections (PJI) and underwent one-stage revision; conversely, negative findings led to the discontinuation of intravenous and local antibiotics therapy. RESULTS: Among the cohort of 22 patients, bacterial cultures yielded negative results, while mNGS identified bacterial infection in 14 patients (63.63%), viral infection in 1 patient (4.55%), and yielded negative results in 7 patients (31.82%). All surgical incisions achieved per primam. Subsequent follow-up assessments conducted for more than 1 year postoperatively revealed absence of PJI among the patients, all of whom exhibited satisfactory progress in their rehabilitation exercises. Notably, the Knee Society Score (KSS) for knee joint patients significantly improved from a preoperative mean of 48.7 ± 3.3 points to 84.3 ± 2.2 points postoperatively, whereas the Harris Hip Score for hip joint patients increased significantly from preoperative mean of 50.6 ± 3.6 points to 87.1 ± 1.6 points (P < 0.01). CONCLUSION: In cases where patients present with unexplained elevations in ESR and CRP levels, primary artificial joint replacement can be undertaken following a one-stage revision approach for PJI.

Cardiovascular Implantable Electronic Device Infections: A Contemporary Review.

Infections associated with cardiac implantable electronic devices (CIEDs) are increasing and are a cause of significant morbidity and mortality. This article summarizes the latest updates with respect to the epidemiology, microbiology, and risk factors for CIED-related infections. It also covers important considerations regarding the diagnosis, management, and prevention of these infections. Newer technologies such as leadless pacemakers and subcutaneous implantable cardioverters and defibrillators are discussed.

Prosthetic Valve Endocarditis Caused by Pasteurella dagmatis, Germany.

An 81-year-old male patient in Germany had prosthetic valve endocarditis caused by Pasteurella dagmatis after a domestic cat bite. We surgically treated a paravalvular abscess and administered definitive antibiotic therapy consisting of penicillin G and levofloxacin. The patient was discharged from the intensive care unit in good condition 21 days after the surgery.

Antimicrobial susceptibility testing of bone and joint pathogens using isothermal microcalorimetry.

The rise in osteomyelitis and periprosthetic joint infections, in combination with increasing life expectancy and the prevalence of diabetes, underscores the urgent need for rapid and accurate diagnostic tools. Conventional culture-based methods are often time-consuming and prone to false-negatives, leading to prolonged and inappropriate antibiotic treatments. This study aims to improve osteomyelitis diagnostics by decreasing the time to detection and the time to an antibiotic susceptibility result to enable a targeted treatment using isothermal microcalorimetry (IMC). IMC measures heat flow in real-time, providing insights into bacterial metabolism without the need for labeling. Using clinical isolates from bone infections, assessing their response to antibiotics through IMC, we demonstrated that IMC could detect bacteria within 4 h and determine antimicrobial susceptibility profiles within 2-22 h (median 4.85, range 1.28-21.78). This is significantly faster than traditional methods. A decision tree, based on antibiotic susceptibility, accurately categorized pathogens, achieving high accuracy (74-100%), sensitivity (100%), and specificity (65-100%). These findings suggest that IMC could redefine diagnostics of bone and joint infections and potentially infections in general, offering timely and precise treatment guidance, thereby improving patient outcomes and reducing health care burdens. Further optimization and clinical validation are needed to fully integrate IMC into routine diagnostics.

Can pre-analytical procedures improve microbiological culture yield in patients with periprosthetic infections?

BACKGROUND: The detection of causative pathogens plays a crucial role in the diagnosis and targeted treatment of periprosthetic joint infections (PJI). While there have been improvements in analytic methods in the past, pre-analytical procedures have not yet been sufficiently investigated. The objective of this study was to compare the culture yield of four different pre-analytical procedures. METHODS: Patients with perioperative diagnosis of PJI were included in a single center cross-sectional study (2021-2022). Tissue samples (n = 20) of each patient were randomly and equally distributed to each of the four study arms. Tissue samples were either send to the laboratory without culture medium (group A) or were transported in thioglycolate medium immediately after sampling at three different temperatures (room temperature, 4 °C, 37° for 24 h; group B-D). Culture media were investigated for growth on days 1, 3, 7, 12, 14. All organisms, the number of positive samples and the time to positivity were recorded and compared between the study arms. Single positive cultures were considered as contamination. RESULTS: In total, 71 patients were included. The proportions of culture negative samples (10-15%) and polymicrobial infections (51-54%) were comparable between the four arms. Seven patients (10%) were culture-negative in group A, but showed growth in thioglycolate media (group B-D). Furthermore, 13% of patients showed growth in all groups, but additional organisms were cultured in thioglycolate. There was growth beyond day 7 of culturing only in thioglycolate, but not in group A. A storage temperature of 4 °C showed a longer time to positivity compared to the other groups (p < 0.001). CONCLUSIONS: Pre-analytical storage of tissue samples in thioglycolate broth did not improve the culture yield and did not detect additional cases of infection compared to the standard (pre-analytical storage in sterile containers). However, including a thioglycolate medium to the sampling algorithm reduced the rate of culture-negative infections and helped to identify additional organisms.

Assessing the predictive value of pre- and post-operative inflammatory markers in patients undergoing total knee arthroplasty.

BACKGROUND AND OBJECTIVE: Total Knee Arthroplasty (TKA) has proven highly effective in improving quality of life for patients with severe knee conditions. Despite advancements, surgical complications such as periprosthetic joint infections (PJIs) pose risks. The potential predictive value of pre- and post-operative inflammatory markers like neutrophil-to-lymphocyte ratio (NLR), D-dimer, and albumin levels on surgical outcomes is garnering attention. There is a growing interest in leveraging these markers to enhance patient selection and outcome prediction in the context of TKA.Focusing on the natural course of these markers, and the incidence of PJIs and to refine perioperative care strategies, improve patient outcomes, and identify high-risk patients for targeted intervention. METHODS: The study included 94 patients who underwent total knee arthroplasty (TKA) between 2019 and 2023. Blood tests were conducted before surgery and at 1, 3, 7, and 15 days after surgery to assess various parameters including white blood cell count, neutrophils, lymphocytes, platelets, hemoglobin, C-reactive protein, D-dimers, total protein, albumin, and total cholesterol values and ratios. RESULTS: Following total knee arthroplasty (TKA), key observations in blood markers included a sharp rise in white blood cell (WBC) counts from 5.81 to 10.22 (*10^9/L) on the first day post-surgery, with levels returning close to preoperative values by day-15. Neutrophil counts similarly increased from 3.46 to 8.50 (*10^9/L) on day-1, decreasing to 4.01 by day-15. Hemoglobin levels significantly decreased from 115.70 g/L to 90.62 by day-3 before improving to 100.30 by day-15. C-reactive protein (CRP) levels also saw a significant rise from 6.15 mg/L to a peak of 47.07 on day-3, then reducing to 10.55 by day-15, indicating a response to inflammation. CONCLUSION: Following total knee arthroplasty (TKA), a significant initial postoperative increase in white blood cell count, neutrophils, and C-reactive protein levels, indicative of an acute inflammatory response, before returning towards baseline values by day 15. Hemoglobin levels displayed a notable dip post-surgery, gradually improving by the study's end. These patterns emphasize the dynamic nature of inflammatory and hematological responses after TKA, highlighting their potential role in predicting surgical outcomes and guiding postoperative care.

Vascular Graft Infections: Updates on a Challenging Problem.

Vascular graft infections (VGI) pose a significant challenge in vascular surgery, characterized by substantial morbidity and mortality. This review delves into the epidemiology, pathogenesis, microbiology, risk factors, and clinical presentation of VGI. It highlights diagnostic criteria and methodologies, including imaging techniques and laboratory tests. Comprehensive management strategies, involving antimicrobial therapy, surgical intervention, and preventive measures, are discussed. Emphasis is placed on the multidisciplinary approach required for effective treatment, alongside emerging trends in VGI microbiology and innovative therapeutic options. This review article aims to provide a detailed understanding of VGI for improved clinical outcomes.

Periprosthetic Joint Infection: What's New?

Total joint arthroplasty (TJA) ranks among the most commonly performed orthopedic surgeries, with its annual incidence on the rise globally. Periprosthetic joint infection (PJI) remains a leading cause of arthroplasty failure. This review aims to summarize recent literature updates on the epidemiology, diagnosis, and management of PJI.

Infections in Patients with Mechanical Circulatory Support.

Patients on mechanical circulatory support are at heightened risk for infection given the invasive nature of the devices with internal and external components, the surgical implantation of the devices, and the presence of foreign material susceptible to biofilm formation. This review discusses the new International Society for Heart and Lung Transplantation mechanical circulatory support device infection definitions, inclusive of durable and acute mechanical circulatory support infections, and describes their epidemiology, diagnosis, and management. A multidisciplinary approach is essential for optimal management. Timing of transplantation in the context of active infection is addressed, and areas of future research are highlighted.

State-of-the-Art Metagenomic Sequencing and Its Role in the Diagnosis of Periprosthetic Joint Infections.

Metagenomic next-generation sequencing (mNGS) is increasingly being recognized as a valuable diagnostic tool for periprosthetic joint infections (PJIs). This study reviews the diagnostic utility of mNGS, highlighting its improved sensitivity in detecting pathogens, particularly in culture-negative and polymicrobial infections. However, the clinical application of this method is hindered by challenges such as the prevalence of host DNA, the necessity for extensive bioinformatic analysis, and the potential for contamination, which can lead to misinterpretation of results. As mNGS continues to evolve, it holds significant potential to improve the management of PJI and enhance the application of precision medicine in orthopedic infections.

The presence of a sinus tract is associated with reinfection after two-stage revision surgery for prosthetic hip joint infection: a case-control study.

BACKGROUND: Reinfection rates after two-stage revision (TSR) for prosthetic joint infection (PJI) range from 7.9 to 14%. Many factors, including sinus tracts, are associated with reinfection after this procedure. This study aimed to delineate whether the presence of sinus tract could increase reinfection rate after TSR and to investigate other potential risk factors for reinfection after TSR. METHODS: We conducted a case-control study by retrospectively reviewing patients who underwent TSR for prosthetic hip joint infection from 2002 to 2022. The case group included patients who developed reinfection after TSR, while the control group consisted of patients who did not experience reinfection. PJI and reinfection after TSR were defined based on Delphi-based international consensus criteria. Patient demographics, past medical history, clinical manifestations, laboratory results, interval between stages, microbiological culture results were collected. Univariate analyses were utilized to assess the effect of sinus tract on reinfection and to identify other risk factors for reinfection after TSR. RESULTS: Six patients with reinfection after TSR were included as the case group and 32 patients without reinfection were in the control group. Significant difference was observed in percentage of patients with sinus tracts between the two groups (67% in the case group versus 19% in the control group, p = 0.031, OR = 8.7). Significant difference was also found in percentage of patients with positive cultures of synovial fluid and synovium harvested during the first-stage revision between the two groups (100% in the case group versus 50% in the control group, p = 0.030). Additionally, patients in the case group had a significantly higher C-reactive protein (CRP) level prior to the second stage revision than that of patients in the control group (8.80 mg/L versus 2.36 mg/L, p = 0.005), despite normal CRP levels in all patients. CONCLUSIONS: Our study revealed that the presence of sinus tracts could significantly increase risk of postoperative reinfection after TSR. Positive cultures during the first stage revision and elevated CRP level prior to the second stage revision could also increase the risk of reinfection after TSR. Further studies with a larger sample size are required. TRIAL REGISTRATION: Retrospectively registered.

Dysregulated neutrophil extracellular traps and haemostatic biomarkers as diagnostic tools and therapeutic targets in periprosthetic joint infection.

Aims: Bacterial infection activates neutrophils to release neutrophil extracellular traps (NETs) in bacterial biofilms of periprosthetic joint infections (PJIs). The aim of this study was to evaluate the increase in NET activation and release (NETosis) and haemostasis markers in the plasma of patients with PJI, to evaluate whether such plasma induces the activation of neutrophils, to ascertain whether increased NETosis is also mediated by reduced DNaseI activity, to explore novel therapeutic interventions for NETosis in PJI in vitro, and to evaluate the potential diagnostic use of these markers. Methods: We prospectively recruited 107 patients in the preoperative period of prosthetic surgery, 71 with a suspicion of PJI and 36 who underwent arthroplasty for non-septic indications as controls, and obtained citrated plasma. PJI was confirmed in 50 patients. We measured NET markers, inflammation markers, DNaseI activity, haemostatic markers, and the thrombin generation test (TGT). We analyzed the ability of plasma from confirmed PJI and controls to induce NETosis and to degrade in vitro-generated NETs, and explored the therapeutic restoration of the impairment to degrade NETs of PJI plasma with recombinant human DNaseI. Finally, we assessed the contribution of these markers to the diagnosis of PJI. Results: Patients with confirmed PJI had significantly increased levels of NET markers (cfDNA (p < 0.001), calprotectin (p < 0.001), and neutrophil elastase (p = 0.022)) and inflammation markers (IL-6; p < 0.001) in plasma. Moreover, the plasma of patients with PJI induced significantly more neutrophil activation than the plasma of the controls (p < 0.001) independently of tumour necrosis factor alpha. Patients with PJI also had a reduced DNaseI activity in plasma (p < 0.001), leading to a significantly impaired degradation of NETs (p < 0.001). This could be therapeutically restored with recombinant human DNaseI to the level in the controls. We developed a model to improve the diagnosis of PJI with cfDNA, calprotectin, and the start tail of TGT as predictors, though cfDNA alone achieved a good prediction and is simpler to measure. Conclusion: We confirmed that patients with PJI have an increased level of NETosis in plasma. Their plasma both induced NET release and had an impaired ability to degrade NETs mediated by a reduced DNaseI activity. This can be therapeutically restored in vitro with the approved Dornase alfa, Pulmozyme, which may allow novel methods of treatment. A combination of NETs and haemostatic biomarkers could improve the diagnosis of PJI, especially those patients in whom this diagnosis is uncertain.