Chronic Periprosthetic Joint Infection Research Articles

Clinical and Radiographic Outcomes of a Long Cementless Monobloc Stem for Revision Total Hip Arthroplasty Due to Chronic Periprosthetic Infection

BackgroundA long cementless monobloc stem is widely used for aseptic loosening, with satisfactory five-to-ten-year outcomes reported. Nonetheless, related studies on chronic periprosthetic joint infection (PJI) are scant. This study evaluated the clinical and radiographic outcomes of the stem in two-stage revisions due to PJI. MethodsThis prospective multicenter cohort study consisted of patients from three medical centers who were enrolled in a single arm from January 2017 to May 2022. All patients were diagnosed with chronic PJI based on International Consensus Meeting (ICM) criteria and underwent two-stage revisions using a long monobloc cementless revision stem. Among 44 patients, 37 (12 women and 25 men) completed an average follow-up of 35.6 months (range, 14 to 75). The primary outcome was the stability of the stem; secondary outcomes included infection eradication, Harris hip score, leg length discrepancy, major complications, and isolated pathogens at intraoperative cultures. ResultsAt one year after revision, the infection-free prosthesis survival rate was 97.3% (95% CI [confidence interval]: 96.4 to 98.2%). At the last follow-up, the mean subsidence was 2.9 ± 2.1 mm (range, 0.8 to 4.8). Postoperative leg length discrepancy averaged −4.6 ± 4.9 mm (range, −16 to 0). The Engh score averaged 14.1 ± 6.9 (range, 0 to 22). The Harris hip score improved from a preoperative average of 35.7 ± 8.5 (range, 12 to 50) to 80.4 ± 9.3 (range, 58 to 92) at the 1-year postoperative follow-up (P < 0.01). ConclusionThe long cementless monobloc stem used in the current study presents a feasible option for two-stage revision in cases of chronic PJI. The bone ingrowth and stability could be observed within the short follow-up time.

Can "LITE" Procedure Combined With a Short Course Antibiotic Treatment Be Effective in Treating the Chronic PJI?-A Prospective Randomized Controlled Trial.

The prevailing treatment for chronic periprosthetic joint infection (PJI) is a two-stage exchange, yet the optimal duration of antibiotic therapy following this procedure remains a topic of debate. This study aimed to determine whether a short course of postoperative antibiotic therapy can maintain infection control rates following a long interval two-stage exchange (LITE) for PJI. We conducted a prospective study enrolling patients with chronic PJI who underwent the LITE procedure at our institution from April 2018 to November 2021. Patients were randomly assigned to receive either a long course (12 weeks) or short course (2 weeks) of postoperative antibiotics. The pathogens, antibiotics, inflammatory markers, antibiotic-related complications, cases of reinfection, or re-operation were recorded. Continuous variables were analyzed using the two-sample t-test or Mann-Whitney U test, and categorical variables were analyzed using Fisher's exact tests. Kaplan-Meier survival analysis was used to compare infection control rates. A total of 60 patients with chronic PJI who completed the LITE procedure were included in the study (30 patients per group). All patients were followed for a minimum of 24 months (mean 39.2 ± 13.0 months). We observed that the infection control rate in the short-course group was not inferior to that in the long-course group (96.7% vs. 96.7%, p = 1.000). For patients with chronic PJI undergoing the LITE procedure, a 2-week course of postoperative antibiotics suffices to maintain infection control rates. Chinese Clinical Trial Registry: ChiCTR1900027089.

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

BackgroundEarly 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.MethodsA 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.ResultsMultivariate 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.ConclusionThe 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.

Can a 1.5-Stage Revision be an Effective Alternative for Chronic Periprosthetic Hip and Knee Infections? A Systematic Review and Meta‐Analysis

BackgroundA 1.5-stage revision could be an alternative to a 2-stage revision for treating hip and knee chronic periprosthetic infections, guaranteeing the maintenance of joint function and infection control and preventing infection-free patients from undergoing further surgery. Our systematic review aimed to answer several questions about the indication, the infection eradication rate, and the long-term functional outcome of 1.5-stage revisions used to treat chronic periprosthetic infections of the hip and knee. MethodsA systematic review of the literature was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, including studies dealing with the use of 1.5-stage and two-stage surgery for chronic periprosthetic joint infection (PJI) following total knee arthroplasty (TKA) or total hip arthroplasty (THA). The Coleman Methodology Score and the Methodological Index for Non-randomized Studies (MINORS) score were used to assess the quality of the studies. A meta-analysis was performed to evaluate the infection eradication rate using either the 1.5-stage revision or the two-stage technique. A total of 494 patients (111 hips and 385 knees) who underwent 1.5-stage with a mean age of 69 years (range, 61 to 82) were identified in the ten included studies. ResultsThe most common cause of reoperation was the conversion to the definitive prosthesis, followed by aseptic loosening. Infection control was reached in 84.6% of the 1.5-stage and 76.1% of the two-stage cohorts. The infection recurrence rate was higher in the two-stage cohort than the 1.5-stage group (21.8 versus 14.3%). ConclusionThe 1.5-stage technique represents a valid treatment option in selected patients who have chronic PJI who cannot undergo further surgeries, adding together the benefits of the one- and two-stage procedures. Furthermore, the 1.5-stage showed a better success rate in the infection resolution than the two-stage technique.

Differences in Success Rate of Two-Stage Revision for Periprosthetic Joint Infection of the Knee Depending on the Applied Definition

BackgroundSuccess rates of two-stage exchange arthroplasty are subject to substantial variance in the literature. An explanation is the lack of a universally accepted definition of what constitutes treatment success for periprosthetic joint infection. Therefore, the main objective of this study was to assess success rates, applying four definitions to identify the one definition that best captures “true” success from both a clinical and patient-centered perspective. MethodsThis was a retrospective study investigating the outcome of a consecutive series of 78 chronic knee periprosthetic joint infections that were treated with a two-stage revision at a single center between 2017 and 2020. Kaplan-Meier survival analyses were conducted to estimate success rates. ResultsAfter a mean follow-up of 36 months (range, 25 to 60), 64 patients (82%) were reimplanted after a mean interim period of 90 days (range, 22 to 201). There was one patient (1%) lost to follow-up, and the overall mortality was 15% (n = 12). Kaplan-Meier survival analyses were used to estimate treatment success at two and three years: implant survival was 93% (95% confidence interval [CI]: 82 to 97) and 87% (95% CI: 73 to 94), infection control was 90% (95% CI: 79 to 95) and 87% (95% CI: 73 to 93), success according to Delphi criteria was 88% (95% CI: 78 to 94), and success according to Musculoskeletal Infection Society criteria was 65% (95% CI: 53 to 74) at both timepoints. ConclusionsSuccess rates were ranging between 65 and 93% depending on the applied definition, highlighting the need for universal success criteria. This variability mainly results from the differing approaches to patients who did not undergo reimplantation or passed away within a year of surgery. These patients exemplify cases of fatal treatment failures. Consequently, the Musculoskeletal Infection Society criteria should be routinely employed to accurately report the “true” success rate.

Biofilm Formation is Durably Prevented on Pre-Fabricated Antibiotic Cement Spacers Compared to Cobalt Chrome and Polyethylene

BackgroundA 2-stage revision remains the standard for managing chronic periprosthetic joint infection. Despite multiple spacer options, whether a particular one better resists biofilm formation remains unclear. Prefabricated polymethylmethacrylate (PMMA) articulating spacers containing antibiotics and a proprietary pore structure were developed to increase antibiotic elution characterized by a rapid burst phase for the initial one to two days and an extended slow-release phase for > 28 days. This in vitro study determined whether biofilm formation is prevented during the initial rapid burst phase and/or the slow-release phase. MethodsS. aureus-Xen36 was incubated in 1.5 mL of Luria-Bertani broth with PMMA discs with the proprietary pore structure either with or without gentamycin and vancomycin or with ‘Hoffman style’ positive-control discs (ultra-high molecular weight polyethylene or cobalt-chrome). Nonadherent bacteria were removed by three phosphate buffered saline rinses every 20 to 24 hours. Planktonic bacterial growth in the culture broth and biofilm formation on the discs were measured by colony forming unit (CFU) counting and resazurin reduction assays. Experiments were repeated > four times. ResultsNo detectable planktonic bacterial growth or biofilm formation occurred in cultures containing PMMA with antibiotics (≤ 15 CFUs/disc), whereas biofilms formed on PMMA without antibiotics, ultra-high molecular weight polyethylene, and cobalt-chrome (1 × 107 to 4 × 108 CFUs/disc, P < 0.0001). Biofilm formation was confirmed by a 100-fold decrease in sensitivity to vancomycin. To determine whether the antibiotic slow-release phase is sufficient to block biofilm formation, PMMA discs with antibiotics were preeluted for 14 days with multiple saline changes prior to bacterial inoculation. After antibiotic elution, still no detectable biofilms formed on PMMA discs with antibiotics (≤ 15 CFUs/disc, P < 0.0001). ConclusionsAntibiotic release during both the initial and slow-release phases prevented biofilm formation on PMMA with the proprietary pore structure. This may translate into improved infection eradication rates clinically.

EFFECTIVE TREATMENT OF SINGLE-STAGE REVISION USING NON-CONTACT LOW FREQUENCY ULTRASONIC DEBRIDEMENT IN TREATING PERIPROSTHETIC JOINT INFECTIONS: A PROSPECTIVE CLINICAL STUDY

Traditional mechanical debridement can only remove visibly infected tissue and is unable to completely clear all the biofilm that hides within muscle crevices and nerves. This study aims to determine the results of single-stage revision using noncontact low frequency ultrasonic debridement in treating chronic periprosthetic joint infections (PJI).A prospective study of consecutive patients requiring single-stage revision for chronic PJI was performed since August 2021. After mechanical debridement, an 8‑mm handheld non‑contact low‑frequency ultrasound probe was used for ultrasonic debridement at a frequency of (25±5) kHz and power of 90% for 5 minutes. Each ultrasound lasted 10 seconds with 3‑seconds intervals. The probe was repeatedly sonicated among all soft tissue and bsingle interface. The distal femoral canal and the posterior capsule of the knee were fully sonicated with a special right‑angle probe. Chemical debridement was then performed to irrigation the whole operative area. Recurrence of infection, culture results and number of colonies 24 hours after ultrasonic debridement were recorded.A total of 45 patients (25 hips and 20 knees) were included and 43 of them (95.6%) were free of infection at a mean follow-up time of 29 months (24 to 33). There were no intraoperative complications related to ultrasonic debridement (neurovascular and muscle injury, poor wound healing and fat liquefaction). The culture‑positive rate of wound liquid before ultrasonic debridement was 40.0% (18/45), which significantly increased to 75.6% (34/45) after ultrasonic debridement (P=0.001). The median number of colonies 24 hours after ultrasonic debridement was 2372 CFU/ml (310 to 4340 CFU/ml), which was significantly higher than that before debridement (307 CFU/ml; 10 to 980 CFU/ml) (P=0.000).Single-stage revision with non‑contact low‑frequency ultrasonic debridement can fully expose bacteria within biofilm, increase the efficacy of chemical debridement and lead to a favorable short‑term outcome without related complications.

Serum albumin-to-globulin ratio and CRP-to-albumin ratio did not outperform serum CRP in diagnosing periprosthetic joint infections.

Serum inflammatory parameters are widely used to aid in diagnosing a periprosthetic joint infection (PJI). Due to their limited performances in the literature, novel and more accurate biomarkers are needed. Serum albumin-to-globulin ratio (AGR) and serum CRP-to-albumin ratio (CAR) have previously been proposed as potential new parameters, but results were mixed. The aim of this study was to assess the diagnostic accuracy of AGR and CAR in diagnosing PJI and to compare them to the established and widely used marker CRP. From 2015 to 2022, a consecutive series of 275 cases of revision total hip (n = 129) and knee arthroplasty (n = 146) were included in this retrospective cohort study. Based on the 2021 European Bone and Joint Infection Society (EBJIS) definition, 144 arthroplasties were classified as septic. Using receiver operating characteristic curve (ROC) analysis, the ideal thresholds and diagnostic performances were calculated. The areas under the curve (AUCs) were compared using the z-test. AGR, CAR, and CRP were associated with PJI (p < 0.001). Sensitivities were 62.5% (95% CI 54.3 to 70.0), 73.6% (95% CI 65.8 to 80.1), and 71.5% (95% CI 63.6 to 78.3), respectively. Specificities were calculated with 84.7% (95% CI 77.5 to 89.9), 86.3% (95% CI 79.2 to 91.2), and 87.8% (95% CI 80.9 to 92.4), respectively. The AUC of CRP (0.797 (95% CI 0.750 to 0.843)) was significantly higher than the AUC of AGR (0.736 (95% CI 0.686 to 0.786), p < 0.001), and similar to AUC of CAR (0.799 (95% CI 0.753 to 0.846), p = 0.832). Decreased sensitivities were observed in PJIs caused by low-virulence organisms (AGR: 60%, CAR: 78%) compared to high-virulence pathogens (AGR: 80%, p = 0.042; CAR: 88%, p = 0.158). Higher sensitivities were seen in acute haematogenous (AGR: 83%, CAR: 96%) compared to chronic PJIs (AGR: 54%, p = 0.001; CAR: 65%, p < 0.001). Serum AGR and CAR showed limited diagnostic accuracy (especially in low-grade and chronic infections) and did not outperform the established marker CRP in our study. Hence, neither parameter can be recommended as an additional tool for diagnosing PJI.

Hypoalbuminemia is Highly Prevalent in Patients with Periprosthetic Joint Infection and Strongly Associated with Treatment Failure.

The role of hypoalbuminemia throughout the course of chronic periprosthetic joint infection (PJI) remains poorly understood. This study aimed to determine the prevalence and risk factors of hypoalbuminemia in periprosthetic joint infection (PJI) patients and to explore the association between hypoalbuminemia and treatment outcomes. This retrospective cohort study included 387 PJI cases who underwent two-stage exchange arthroplasty between January 2007 and August 2020, of which 342 were reimplanted. The mean follow-up period was 7.9 years. Multivariate logistic regression analyses were performed to identify risk factors for hypoalbuminemia and to assess the effect of hypoalbuminemia at 1st- and 2nd-stage exchange on the treatment outcome. Furthermore, the impact of dynamic changes in hypoalbuminemia was investigated. The prevalence of hypoalbuminemia at 1st- and 2nd-stage exchange was 22.2% and 4.7%, respectively. Patients with age ≥ 68 years and those with isolation of Staphylococcus aureus, Streptococcus, or Gram-negative bacteria exhibited a higher risk of hypoalbuminemia. Hypoalbuminemia at 1st-stage was significantly related to treatment failure (OR = 3.3), while hypoalbuminemia at 2nd-stage raised the OR to 10.0. Patients with persistent hypoalbuminemia at both the 1st- and 2nd-stage exchanges had a significantly higher rate of treatment failure than patients with hypoalbuminemia at the 1st-stage but normal albumin levels at the 2nd-stage exchange (55.6% vs 20.0%, p = 0.036). One in five patients with chronic PJI exhibits hypoalbuminemia. Hypoalbuminemia is more likely to develop in patients of advanced age and those infected by specific highly virulent organisms. Also, our results highlight the close association between hypoalbuminemia and treatment outcomes.

The role of BioFire Joint Infection Panel in diagnosing periprosthetic hip and knee joint infections in patients with unclear conventional microbiological results.

This study aimed to evaluate the BioFire Joint Infection (JI) Panel in cases of hip and knee periprosthetic joint infection (PJI) where conventional microbiology is unclear, and to assess its role as a complementary intraoperative diagnostic tool. Five groups representing common microbiological scenarios in hip and knee revision arthroplasty were selected from our arthroplasty registry, prospectively maintained PJI databases, and biobank: 1) unexpected-negative cultures (UNCs), 2) unexpected-positive cultures (UPCs), 3) single-positive intraoperative cultures (SPCs), and 4) clearly septic and 5) aseptic cases. In total, 268 archived synovial fluid samples from 195 patients who underwent acute/chronic revision total hip or knee arthroplasty were included. Cases were classified according to the International Consensus Meeting 2018 criteria. JI panel evaluation of synovial fluid was performed, and the results were compared with cultures. The JI panel detected microorganisms in 7/48 (14.5%) and 15/67 (22.4%) cases related to UNCs and SPCs, respectively, but not in cases of UPCs. The correlation between JI panel detection and infection classification criteria for early/late acute and chronic PJI was 46.6%, 73%, and 40%, respectively. Overall, the JI panel identified 12.6% additional microorganisms and three new species. The JI panel pathogen identification showed a sensitivity and specificity of 41.4% (95% confidence interval (CI) 33.7 to 49.5) and 91.1% (95% CI 84.7 to 94.9), respectively. In total, 19/195 (9.7%) could have been managed differently and more accurately upon JI panel evaluation. Despite its microbial limitation, JI panel demonstrated clinical usefulness by complementing the traditional methods based on multiple cultures, particularly in PJI with unclear microbiological results.

The Impact of Culture Negativity on the Outcomes of Revision Total Knee Arthroplasty for Chronic PJI.

Culture-positive (CP) and culture-negative (CN) periprosthetic joint infections (PJI) remain a crucial area of research; however, current studies comparing these infections rely on unstandardized outcome reporting tools. Our study aimed to compare the outcomes of two-stage revision of CP and CN PJI using the standardized Musculoskeletal Infection Society (MSIS) outcome reporting tool. We retrospectively reviewed 138 patients who were diagnosed with PJI and indicated for two-stage revision total knee arthroplasty (rTKA). The majority of patients in both CP and CN cohorts achieved infection control without the need for reoperation (54.1% and 62.5%, respectively). There was a significant difference in the overall distribution of MSIS outcomes (p = 0.043), with a significantly greater rate of CN patients falling into Tier 1 (infection control without the use of suppressive antibiotics) (52.5% versus 29.6%, p = 0.011). There was also a significant difference in the distribution of septic versus aseptic reoperations after 2nd stage (p = 0.013), with more CP reoperations being septic and more CN reoperations being aseptic. The duration from first to second stage was significantly shorter in the CN cohort (p = 0.002). While overall infection control was similar between cohorts, these data suggest that the outcomes of two-stage rTKA are favorable in cases of CN PJI.

Use of Hinged Implants for Multistage Revision Knee Arthroplasty for Severe Periprosthetic Joint Infection: Remission Rate and Outcomes After a Minimum Follow-Up of 5 Years

BackgroundIn severe periprosthetic joint infection after total knee arthroplasty (TKA), multistage procedures are indicated for ongoing signs of infection after implant removal during the spacer interval of an intended 2-stage exchange. In these cases, several additional debridement and spacer exchange surgeries may be necessary. Herein, we analyzed the complications, remission rates, and functional outcomes after multistage revision arthroplasty using hinged TKAs. MethodsPatients (n = 79) treated with multistage revision arthroplasty after chronic periprosthetic joint infection of the knee were included (2010 to 2018). During the prosthesis-free interval, a static spacer containing antibiotic-loaded bone cement was implanted. The mean number of surgeries, including implant removal and revision arthroplasty, was 3.8 (range, 3 to 8). The mean duration from implant removal to revision arthroplasty was 83 days (range, 49 to 318). Complications, remission, and mortality were analyzed after a minimum follow-up of 5 years. Outcomes were assessed based on the Knee Society Score (KSS) and the Western Ontario McMasters University Osteoarthritis Index. ResultsDuring follow-up, 24 (30.4%) patients underwent revision surgery, with a mean time to surgical revision of 99 weeks (range, 1 to 261). After follow-up, the infection-free remission rate and overall mortality were 87.3 and 11.4%, respectively. The mean KSS was 74.3 (range, 24 to 99), the KSS Function Score was 60.8 (range, 5 to 100), and the Western Ontario McMasters University Osteoarthritis Index 30.2 (range, 5 to 83). ConclusionsIn difficult-to-treat cases, multistage revision arthroplasty showed high remission rates and low mortality after a follow-up of 5 years. The overall revision rate was comparably high, accounting for early and late reinfections most of the time. In cases of implant survival, functional outcomes comparable to those of revision hinge TKA reported in the literature can be achieved. Therefore, multistage procedures with additional debridement steps should be performed in cases of ongoing infections in intended 2-stage procedures.

Risk Factors and Microbiological Profile of Knee Periprosthetic Joint Infections With Sinus Tract

BackgroundA sinus tract is an abnormal channel that communicates between the skin and the joint, and meets one of the major criteria that is diagnostic of periprosthetic joint infection (PJI). The purpose of this study was to compare the risk factors and the microorganism profile of PJI of the knee with an overlying sinus tract to PJI without a sinus tract. MethodsThis was a retrospective case-control study of PJI following total knee arthroplasty with and without the presence of an overlying sinus tract from 1996 to 2020. There were 2,685 unique cases of chronic PJI following total knee arthroplasty, of which 405 cases (15.1%) had a sinus tract and 2,280 cases (84.9%) did not. Univariate and multivariate analyses were performed to evaluate risk factors and the microorganism profiles of the 2 groups. Odds ratios with 95% confidence intervals were reported. ResultsAfter adjusting for potential confounders in the multivariate analysis, the presence of a sinus tract was associated with a history of severe liver disease (P = .039; odds ratio: 1.99; 95% confidence interval: 1.04 to 3.84). Polymicrobial infections comprised 41.7% of PJI in the sinus tract group, compared to 29.1% in patients who did not have a sinus tract (P < .001). Of the monomicrobial PJI, Staphylococcus aureus (P < .001), Enterococcus faecalis (P < .001), Enterobacter cloacae (P = .002), Corynebacterium species (P = .037), Proteus mirabilis (P = .028), coagulase-negative Staphylococci (P = .019), and Candida albicans (P = .029) were more common in patients who had a sinus tract. ConclusionsThe microbiology profile is significantly different in patients who have PJI of the knee with a sinus tract. These findings can guide the surgeon with surgical planning and selecting the appropriate antibiotic-loaded bone cement and empiric antibiotic treatment.

Targeting Bacterial Persisters via Reactive Oxygen Species‐Generating Hydrogel Microspheres

AbstractThe presence of bacterial persisters is a key factor contributing to chronic infection. However, no effective treatment methods are currently available. Thus, a platform is developed, called reactive oxygen species (ROS) bomb, based on microenvironment‐adaptive hydrogel microspheres, to oxidize the cell membranes of persisters in chronic periprosthetic joint infection (PJI). Fenton reagent hydroxy iron oxide (FeOOH) and a glucose oxidase (GOx)/calcium phosphate (CaP) acid‐responsive shell are sequentially induced on the surface of mesoporous polydopamine (PDA) nanoparticles by the PDA‐mediated ion precipitation and interfacial adhesion, followed by the coloaded with glucose into microfluidic hyaluronic acid hydrogel microspheres. Hydroxyl radicals are explosively generated through GOx‐mediated glucose oxidase, H2O2 production, and its Fenton‐like reactions with FeOOH, which also benefit from the weakly acidic microenvironment around persisters, result in the destruction of bacterial cell membrane, and subsequent overflow of cellular contents such as dsDNA, proteins, and K+. The bactericidal rates of methicillin‐resistant Staphylococcus aureus and Staphylococcus epidermidis persisters are up to 99.14% and 98.96%, and the bacterial loads in lesion location are significantly decreased after ROS bombs treated, effectively alleviated the inflammation and bone resorption damage. This work provides a new strategy toward persisters clearance and shows great application potential in other chronic infection‐related diseases.

Active myeloperoxidase: a promising biomarker to differentiate "acute" and "low-grade" peri-prosthetic joint infections from aseptic failures.

The accurate distinction between periprosthetic joint infections (PJI) and aseptic failures (AF) is of paramount importance due to differences in treatment. However, this could be challenging by using the current criteria. Various synovial fluid biomarkers are being assessed to improve the diagnostic accuracy. Myeloperoxidase (MPO), an enzyme contained in the granules of neutrophils, may be a promising biomarker for PJI. Synovial fluids of 99 patients (n = 65 PJI according to EBJIS criteria; n = 34 AF) were collected in two specialized orthopedic centers. PJI were divided into acute (n = 33) and low-grade (n = 32) according to previously published classification. An activity assay specific for active MPO was performed in each sample. Ability of MPO to correctly discriminate patients with PJI from AF was determined by ROC analysis. The best discriminating cut-off value was determined by calculating the J Youden index. For all analyses, a P value < 0.05 was considered statistically significant. Active MPO was higher in PJI than AF (P < 0.0001). The ROC analysis revealed a significant area under the curve (AUC: 0.86; 95% CI: 0.78-0.93, P < 0.0001). A cut-off value of 561.9 U/mL, with good sensitivity (0.69) and specificity (0.88), discriminated between AF and PJI (accuracy 75.76%, 95% CI: 66.11-83.81%, positive likelihood ratio 5.88, 95% CI: 2.31-14.98 and negative likelihood ratio 0.35, 95%CI: 0.24-0.51). No difference in MPO levels was found between acute and chronic low-grade PJI. The proposed assay appears to be a reliable and affordable tool for detecting the active MPO in synovial fluid, with promising characteristics of sensitivity and specificity in discriminating both acute and low-grade PJI from AF. Further studies are needed to confirm MPO diagnostic cut-off values and validate their use in the routine clinical practice.

Diagnosis and Management of Periprosthetic Joint Infections After Total Ankle Arthroplasty.

Periprosthetic joint infection (PJI) after total ankle arthroplasty (TAA) is a dreaded complication that may lead to catastrophic outcomes. Risk factors include a history of surgery on the operated ankle, low preoperative function scores, diabetes, extended surgical time, and postoperative wound-healing problems. Clinical presentation varies and may include increasing ankle pain and swelling, high temperature, local erythema, wound drainage, and dehiscence. The initial diagnostic evaluation should include plain radiographs, erythrocyte sedimentation rate, C-reactive protein levels, and leukocyte count. In suspected cases with elevated erythrocyte sedimentation rate and C-reactive protein, aspiration of the ankle joint for synovial fluid analysis, Gram staining, and culture should be performed. Antibiotic therapy should be based on the pathogen identified, and the surgical strategy should be determined based on the time lines of PJI. Early PJI can be treated with irrigation and débridement with polyethylene exchange. The surgical treatment of choice for late PJI is two-stage revision arthroplasty, which includes removal of the implant, insertion of an antibiotic spacer, and reimplantation of a TAA. In certain chronic PJI cases, permanent articulating antibiotic spacers can be left in place or an ankle arthrodesis can be performed. Below-knee amputation is considered as the final option after limb-sparing procedures have failed.

Success Rate After 2-Stage Spacer-Free Total Hip Arthroplasty Exchange and Risk Factors for Reinfection: A Prospective Cohort Study of 187 Patients

BackgroundTwo-stage prosthesis exchange is the treatment of choice for chronic periprosthetic joint infection (PJI) of a total hip arthroplasty (THA), especially when the bone and surrounding soft tissues are compromised or difficult-to-treat pathogens are implicated. The aims of our study were as follows: (1) to determine the outcome of 2-stage prosthesis exchange for the treatment of PJI after THA and (2) to determine the risk factors for reinfection leading to subsequent revision surgeries after reimplantation. MethodsWe prospectively enrolled 187 consecutive patients who underwent a 2-stage THA exchange with resection arthroplasty for PJI from 2013 to 2019. The mean (± SD) duration of follow-up was 54.2 ± 24.9 months (range, 36 to 96), and the mean interval until reimplantation was 9.8 ± 8.9 weeks (range, 2 to 38). All patients remained in a spacer-free girdlestone situation between the 2 stages of treatment. Patients who remained infection-free after their 2-stage treatment were considered to have achieved treatment success. ResultsThe overall success rate was 85.6%. The cumulative probability of reinfection was 11.5% after one year and 14% after 2 years after reimplantation. High virulence or difficult-to-treat pathogens were significant and independent risk factors for reinfection (HR [hazard ratio] = 3.71, 95% CI [confidence interval]: 1.47 to 9.36, P = .006 and HR = 3.85, 95% CI: 1.73 to 8.57, respectively, P = .001), as was previous 2-stage hip prosthesis exchange (HR = 3.58, 95% CI: 1.33 to 9.62, P = .01). Overall reoperation and revision rates were 26.2 and 16.6%, respectively. Re-infected patients had an 80% higher probability of reoperation than noninfected ones (P < .001, log-rank = 102.6), and they were 55% more likely to undergo revision surgery during their follow-up (P < .001, log-rank = 55.4). ConclusionsReinfection rates after 2-stage spacer-free THA revision for PJI still remain high but are comparable to those including cement spacers. Patients who have had prior failed 2-stage implant exchanges or are infected by high-grade or difficult-to-treat pathogens are at high risk for treatment failure.

Is there a role of calprotectin testing in the diagnosis of surgical site infections after total hip and knee arthroplasty? A preliminary study.

Recent studies have revealed the usefulness of synovial calprotectin (CLP) in diagnosing chronic periprosthetic joint infections (PJIs). However, there is still a lack of evidence to support the use of serum CLP in the diagnosis of early PJIs and surgical site infections (SSIs) after total joint arthroplasties (TJAs). The primary aim of this study is to investigate the standard kinetics of CLP concentrations in the blood during the very early postoperative period after non-complicated total hip arthroplasty (THA) and total knee arthroplasty (TKA). The secondary aim was to perform a preliminary comparison of CLP concentrations between non-infected patients and patients with recognized SSIs. A total of 64 consecutive patients who underwent primary THA and TKA were included in this prospective research. Sixty patients (30 THA and 30 TKA) were scheduled to determine the standard shape of the blood CLP curve and the expected concentrations during the first 5 postoperative days after non-complicated TJAs. In 4 additonal patients, early SSI was confirmed, and they were included in a separate SSI subgroup. Calprotectin demonstrated a linear increase during the first 5 postoperative days. Statistically significant differences in CLP concentrations between non-infected cases and SSIs were not observed. The preoperative median results with interquartile range (Q1-Q3) were 0.52 (0.39-0.64) mg/dL and 0.5 (0.47-0.52) mg/dL (p = 0.77), while post operation they were as follows: on postoperative day 1: 0.88 (0.53-1.3) mg/dL and 0.86 (0.62-1.1) mg/dL (p = 0.84), on postoperative day 3: 1.77 (1.29-2.08) mg/dL and 1.85 (1.70-1.95) mg/dL (p = 0.72), and on postoperative day 5: 2.32 (1.79-2.67) mg/dL and 2.56 (2.25-2.83) mg/dL (p = 0.55), respectively. Serial CLP measurements during the early postoperative period revealed a linear (statistically significant) increase in concentration to postoperative day 5 without an evident point of decrease. A significant difference in median values and the course of curve patterns between the non-complicated and SSI groups was not observed.

Patient-Reported Outcomes Following Periprosthetic Joint Infection of the Hip and Knee: A Longitudinal, Prospective Observational Study.

The role of patient-reported outcome measures (PROMs) as tools for monitoring the impact and outcomes of periprosthetic joint infection (PJI) is not well described. This study analyzed the Oxford Hip Score (OHS) or Oxford Knee Score (OKS) in a prospective observational cohort of patients with hip or knee PJI. The PIANO (Prosthetic joint Infection in Australia and New Zealand, Observational study) cohort prospectively enrolled patients with newly diagnosed PJI from multiple centers. The OHS and OKS were evaluated at PJI diagnosis (baseline) and at 3, 12, and 24 months. Scores and score changes were examined according to PJI type, patient characteristics, and management. A successful functional outcome at 12 months was defined as an OHS of >38 or OHS of >36 and/or an improvement from baseline of >12 or >9, respectively. Of the 741 participants, PROMs were available at 12 months for 233 with hip and 342 with knee PJI. Significant improvements (p < 0.0001) were seen at 12 months for both the OHS (24.5 to 36) and OKS (25 to 34), with no further improvement at 24 months. Patients with late-acute PJI had a higher median baseline OHS (35; interquartile range [22 to 46]) and OKS (30 [18 to 41]) than those with early PJI (OHS: 19 [15 to 29]; OKS: 22 [16 to 29.5]) or chronic PJI (OHS: 23 [14 to 34]; OKS 22 [14 to 28]). Logistic regression showed that a clinical cure (adjusted odds ratio [aOR] = 1.88, 95% confidence interval [CI] = 1.28 to 2.76, p = 0.001) and early PJI (aOR = 2.56, 95% CI = 1.64 to 4.07, p < 0.0001) independently predicted a successful functional outcome. Chronic renal impairment (aOR = 0.31, 95% CI = 0.13 to 0.71, p = 0.007), congestive cardiac failure (aOR = 0.41, 95% CI = 0.17 to 0.95, p = 0.04), and clinical signs of inflammation (aOR = 0.53, 95% CI = 0.33 to 0.85, p = 0.009) at diagnosis independently predicted failure to achieve a successful functional outcome. The OHS and OKS varied significantly at baseline and 12 months according to PJI type, emphasizing the need to consider the PJI type when evaluating treatment success. This study highlights superior functional outcomes associated with early PJI and with achievement of a clinical cure. Therapeutic Level II . See Instructions for Authors for a complete description of levels of evidence.

Intraoperative calprotectin lateral flow immunoassay can assist decision-making between one- and two-stage revision total hip arthroplasty for patients with suspected periprosthetic joint infection.

Accurate diagnosis of chronic periprosthetic joint infection (PJI) presents a significant challenge for hip surgeons. Preoperative diagnosis is not always easy to establish, making the intraoperative decision-making process crucial in deciding between one- and two-stage revision total hip arthroplasty (THA). Calprotectin is a promising point-of-care novel biomarker that has displayed high accuracy in detecting PJI. We aimed to evaluate the utility of intraoperative calprotectin lateral flow immunoassay (LFI) in THA patients with suspected chronic PJI. The study included 48 THAs in 48 patients with a clinical suspicion of PJI, but who did not meet European Bone and Joint Infection Society (EBJIS) PJI criteria preoperatively, out of 105 patients undergoing revision THA at our institution for possible PJI between November 2020 and December 2022. Intraoperatively, synovial fluid calprotectin was measured with LFI. Cases with calprotectin levels ≥ 50 mg/l were considered infected and treated with two-stage revision THA; in negative cases, one-stage revision was performed. At least five tissue cultures were obtained; the implants removed were sent for sonication. Calprotectin was positive (≥ 50 mg/l) in 27 cases; out of these, 25 had positive tissue cultures and/or sonication. Calprotectin was negative in 21 cases. There was one false negative case, which had positive tissue cultures. Calprotectin showed an area under the curve of 0.917, sensitivity of 96.2%, specificity of 90.9%, positive predictive value of 92.6%, negative predictive value of 95.2%, positive likelihood ratio of 10.6, and negative likelihood ratio of 0.04. Overall, 45/48 patients were correctly diagnosed and treated by our algorithm, which included intraoperative calprotectin measurement. This yielded a 93.8% concordance with postoperatively assessed EBJIS criteria. Calprotectin can be a valuable tool in facilitating the intraoperative decision-making process for cases in which chronic PJI is suspected and diagnosis cannot be established preoperatively.