bluuebunny/crossref_metadata_2025 huggingface dataset:
HIGH FAILURE RATES IN CONCOMITANT PERIPROSTHETIC JOINT INFECTION AND PERIPROSTHETIC FRACTURE TREATMENT: A STUDY OF 41 TOTAL HIP ARTHROPLASTIES
Authors: Jaschke Markus , Goumenos Stavros , Mewes Moritz-Guenther , Perka Carsten , Trampuz Andrej , Meller Sebastian
Published: November 2024

Aim

Periprosthetic joint infection (PJI) and periprosthetic fracture (PF) are one of the most devastating complications in arthroplasty. Each complication by itself is challenging to solve. Yet, simultaneously, both complications are inconceivably complex to deal with, while the treatment regimen of PJI and PF are contradictory. Chronic PJI most often requires implant removal, while PF requires stability, regularly achieved by stable osteosynthesis. This study aims to (1) analyse the success rate of PJI with following concomitant PF during the treatment course in total hip arthroplasties (THA) and (2) to determine the risk factors for reinfection and subsequent revision surgery after treatment of PJI and PF.

Method

This restrospective study analyzed 41 patients with concomitant PJI and PF during the PJI treatment period from 2013 to 2022 involving THA. Patients were divided in two cohorts termed success and failure and were statistically compared. The median follow-up time was 66 months (>12 months). All patients were considered individually and treated according to their individual needs in fracture and infection treatment. Re-arthroplasty survival was analyzed using the Kaplan-Meier method. Relevant risk factors were analyzed using the Mann-Whitney test or Chi-square, depending on the variable's scale.

Results

The overall success rate of our cohort was 70,7%. Twelve patients required re-operation due to reinfection, resulting in a cumulative 12-month-reinfection rate of 19,5%. The estimated cumulative reinfection free survival rate was 68,3%. Significance in risk factors for failure were found in pathogen virulence grade, Difficult to treat pathogen and number of debridement during interval. On average the Harris Hip score was 66 in the group of reinfection compared to 77 in the group of success.

Conclusions

Reoperation and re-infection rate remains high in patients with simultaneous PJI and PF in THA. Due to the heterogeneity of the fractures, soft tissue conditions and pathogens found, treatment must be individualised to salvage the limb. However, small cohorts impact the statistical strength negatively due to instances of two rare complications.
CLINICAL EVIDENCE OF BIOMATERIALS IN OSTEOMYELITIS TREATMENT: LITERATURE REVIEW AND DECISION-MAKING CONSIDERATIONS
Authors: Arts Chris
Published: November 2024

Introduction

Various biomaterials and bone graft substitute technologies for use in osteomyelitis treatment are currently used in clinal practice. They vary in mode of action (with or without antibiotics) and clinical application (one-stage or two-stage surgery). This systematic review aims to compare the clinical evidence of different synthetic antimicrobial bone graft substitutes and antibiotic-loaded carriers in eradicating infection and clinical outcome in patients with chronic osteomyelitis.

Methods

Systematic review according to PRISMA statement on publications 2002-2023. MESH terms: osteomyelitis and bone substitutes. FREE terms: chronic osteomyelitis, bone infection. A standardized data extraction form was be used to extract data from the included papers.

Results

Publications with increased methodological quality and clinical evidence for biomaterials in osteomyelitis treatment were published in the last decades. High 85-95% eradication rates of osteomyelitis were observed for various resorbable Ca-P and/or Ca-S biomaterials combined with antibiotics and S53P4 bioactive glass. Level of evidence varies significantly between products. Antibiotic pharmacokinetic release profiles vary between resorbable Ca-P and/or Ca-S biomaterials.

Conclusion

Given the high 85-95% eradication rates of osteomyelitis by various resorbable Ca-P and/or Ca-S biomaterials combined with antibiotics and S53P4 bioactive glass, one-stage treatment is preferred. Surgeons should be aware of variations in mechanical properties and antibiotic pharmacokinetic release profiles between Ca-P and CA-s products. Mechanical, biological and antimicrobial properties of bioactive glass are formulation dependent. Currently, only S53P4 bioactive glass has proven antimicrobial properties. Based on this systematic review antibiotic loaded fleeces should be used with caution and restraint.
ASSESSING THE EFFICACY OF A PRE-FORMULATED IRRIGATION SOLUTION FOR ACUTE PERIPROSTHETIC JOINT INFECTION: INITIAL FINDINGS FROM A RANDOMIZED CONTROLLED TRIAL
Authors: Taltavull Rafael Oleo , Goma-Camps Matías Vicente , Calderer Lluis Carrera , Amat Carles , Corona Pablo
Published: November 2024

Aim

This study aims to evaluate the effectiveness of a pre-formulated irrigation solution1 (containing ethanol, acetic acid, sodium acetate, benzalkonium chloride, and sterile water) compared to saline solution in managing acute periprosthetic joint infections (A-PJI) during Debridement, Antibiotic, and Implant Retention (DAIR) surgeries. The primary objective is to assess the healing rate using this solution1 versus saline in A-PJI patients, with “cure” defined by a set of criteria including no recurrence, wound issues, or need for ongoing suppressive antibiotics after 1 year. Principio del formularioFinal del formulario

Method

This single-center, randomized controlled trial will involve patients with acute periprosthetic infections undergoing standard DAIR surgery, divided into two groups: one receiving saline solution and the other receiving pre-formulated solution1. The study is single-blinded, with patients unaware of their group assignment. The study is registered at ISRCTN: https://doi.org/10.1186/ISRCTN10873696. Inclusion criteria include patients over 18 with hip or knee prostheses suffering from acute or hematogenous periprosthetic infections, while exclusion criteria include a history of prior debridement or multiple infected implants, among others. Principio del formularioFinal del formulario A total of 50 subjects are needed for statistical significance, with a 5% dropout rate anticipated. An interim safety analysis will assess early effectiveness and adverse effects, and the results are presented in this study. Data will be managed in online databases and analyzed using SPSS software, with a significance level of p<0.05

Results

Twenty-four patients were eligible for analysis, twelve in each group. The overall average age was 75 years, and the gender distribution was predominantly female (9 F and 3 M in each group). No significant differences were found at the baseline characteristics level between the two groups (p>0.05). The minimum follow-up of 1 year was achieved in all cases except three due to deaths not related to periprosthetic infection. Regarding efficacy, a non-statistically significant difference was observed (p>0.05), with 58% in the serum group and 42% in the pre-formulated irrigation solution1 group (X2= 0.17, p=0.683). The average hospital stay was 38.42 days (SD 26.32) in the pre-formulated irrigation solution group1 and 24.42 days (SD 18.72) in the serum group, with this difference being not significant (t=1.5, p=0.148).

Conclusions

While the current analysis indicates no significant differences between both groups in terms of efficacy, the study's ongoing progress and the inclusion of a larger sample size could potentially yield more definitive results.
LIPOSOMES CONJUGATED ON THE BACTERIOPHAGE SURFACE FOR DELIVERING ANTIBIOTICS TO COMBAT MULTIDRUG-RESISTANT BACTERIAL INFECTIONS
Authors: Wang Lei , Trampuz Andrej , Zhang Xianlong
Published: November 2024

Aim

Treatment of prosthetic joint infection (PJI) by systemic administration of high doses of long-term antibiotics often proves ineffective, causing severe side effects. Thus, we presented the phage Sb-1, which coding extracellular polymeric substances (EPS) degradation depolymerases, conjugated with rifampicin-loaded liposomes (Lip-RIF@Phage) by bio-orthogonal functionalization strategy to target biofilm (Figure1).

Method

Methicillin-resistant Staphylococcus aureus (MRSA) biofilm was grown on porous glass beads for 24 h in vitro. After the biofilm formation, beads were exposed to 0.9% saline, then sonication. Quantitative and qualitative biofilm analyses were performed by colony counting, scanning electron microscopy and isothermal microcalorimetry. A rat model of total knee arthroplasty infected with the bioluminescent MRSA strain was developed as the PJI model to evaluate the efficacy of Lip-RIF@Phage anti-biofilm therapy in vivo, then the creatinine, alanine transaminase, and aspartate transaminase values were evaluated throughout the entire treatment process.

Results

After treatment with Lip-RIF@Phage, no bacterial colonies were observed, consistent with findings from scanning electron microscopy. Similarly, isothermal microcalorimetry revealed no detectable heat following Lip-RIF@Phage treatment, aligning with these observations. In vivo experiments demonstrated a significant reduction in biofilm cell load compared to all other tested conditions, with no evidence of systemic toxicity on renal and liver functions attributed to Lip-RIF@Phage.

Conclusions

The innovative depolymerase-phagobot nanosystem (Lip-RIF@Phage) exhibits remarkable efficacy in completely eliminating biofilm cells in vitro. It serves as an excellent carrier for antibiotic delivery, enhancing antibiotic penetration through biofilms and improving biofilm eradication efficacy. Furthermore, it enables personalized treatment strategies against biofilm-associated multidrug-resistant (MDR) infections by maximizing the effectiveness of any remaining sensitive antibiotics.

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IN VITRO STUDY ON CHEMICAL DEBRIDEMENT DURING PERIPROSTHETIC JOINT INFECTION SURGERY: WHAT IS THE BEST TREATMENT STRATEGY?
Authors: Gómez Miguel Márquez , Guembe María , Díaz-Navarro Marta , Peinado Lourdes Prats , Matas-Díaz Jose-Antonio , Ruiz Pablo Sanz
Published: November 2024

Aim

Chemical debridement is a fundamental step during Periprosthetic joint infection (PJI) surgery. Antiseptic solutions are commonly used, but evidence on the optimal antiseptic, concentration, and irrigation time is lacking. The aim of this study is to analyze and compare the anti-biofilm capacity of povidone iodine, H202, acetic acid and Bactisure™ after different exposure times, as well as their combinations.

Method

Surgical steel discs inoculated with methicillin susceptible (MSSA) and resistant S. aureus (MRSA), P. aeruginosa, and S. epidermidis were exposed to the following antiseptic solutions: 0.3% (PI0.3) and 10% povidone iodine (PI10), H202, 3% Acetic acid (AA3) and Bactisure™. Combinations included AA3, H202, and PI10 in various orders. Exposure time for the antiseptics solutions was 1, 3 and 5 minutes, while combinations had a 9-minute total exposure, 3 minutes per antiseptic sequentially. All experiments were performed in triplicate and with a sterile saline control. nThe reduction in colony-forming units (CFU) was measured after sonication, and biofilm structure was analyzed via scanning electron microscopy.

Results

PI showed the highest antibiofilm activity. PI0.3 eradicated bacteria on the discs after 3 and 5 minutes of exposure, but only achieved a 77.1% reduction after 1 minute. After PI10 treatment, we did not recover any bacteria regardless of exposure time. H202, AA3, and Bactisure™ reached a significantly lower bacterial decrease at all exposure times compared to PI0.3 and PI10. AA3 was less effective against MSSA and S. epidermidis. H202 showed less activity against MRSA than PI0.3, PI10, and Bactisure™. Combinations of antiseptics starting with AA3 showed the best results in terms of CFU reduction and cell viability.

Conclusions

We propose a sequential combination of AA3 + H202 + PI10 with an exposure time of 9 minutes for the chemical debridement in PJI surgery. First, AA3 performs debridement and disruption of the biofilm. Then, H202 has a bactericidal effect and increases the porosity of the cell wall, and PI10 has a final bactericidal effect. If combinations are unavailable, PI is a cost-effective alternative.
REVISION FOR INFECTION AFTER PRIMARY TOTAL HIP ARTHROPLASTY: TIME TRENDS IN SURGICAL STRATEGY
Authors: Høvding Pål , Hallan Geir , Furnes Ove , Dale Håvard
Published: November 2024

Background and purpose

Previous publications have reported an increased but levelling out risk of revision for infection after total hip arthroplasty (THA) in Norway. We assessed the changes in risk of major (cup and/or stem, 1- or 2-stage) and minor revisions (debridement, exchange of modular parts, antibiotics and implant retention (DAIR)) for infection after primary THAs reported to the Norwegian Arthroplasty Register (NAR) over the period 2005-2022.

Patients and methods

Primary THAs reported to the NAR from 2005 to 2022 were included. Time was stratified into time periods (2005-2009, 2010-2018, 2019-2022) based on a previous publication. Cox regression analyses, adjusted for sex, age and ASA-classification, with the first revision for infection were performed.

Results

140,338 primary THAs met the inclusion criteria. 1.3% (1,785) were revised for infection during the study period. 0.5% (638) had major revisions, whereas 0.8% (1,147) had DAIRs for infection.

The risk of revision for infection was 1.2 (95%CI 1.1-1.4) for 2010-2018 and 1.0 (0.8-1.1) for 2019-2022 compared to 2005-2009. Compared to 2010-2018, the risk of revision for infection was 0.8 (0.7-0.9) for 2019-2022.

The risk of DAIR for infection was 1.5 (1.3-1.9) for 2010-2018 and 1.2 (1.0-1.4) for 2019-2022 compared to 2005-2009. Compared to 2010-2018, the risk of DAIR for infection was 0.8 (0.7-0.9) for 2019-2022.

The risk of major revision for infection was 0.8 (0.7-1.0) for 2010-2018 and 0.8 (0.6-1.0) for 2019-2022 compared to 2005-2009.

Interpretation

The overall risk of revision for infection after THA, in Norway, has decreased in the period 2019-2022. The risk for DAIR initially increased in the period 2005-2009, levelled out 2010-2018 before starting to decrease in 2019-2022. The risk of major revision for infection was reduced in the period 2005-2009 before levelling out. This shows changes in revision strategies, but may also reflect a true decrease in periprosthetic joint infection.
A THERAPEUTIC DRUG-MONITORING APPROACH FOR DALBAVANCIN (MONTALBANO)
Authors: Landonio Simona , Galli Lucia , Mariani Chiara , Covizzi Alice , Merli Stefania , Giorgi Riccardo , Coen Massimo , Cattaneo Dario , Passerini Matteo , Gori Andrea
Published: November 2024

Aim

dalbavancin, a lipo-glycopeptide antibiotic effective against Gram-positive bacteria (including methicillin-resistant Staphylococcus aureus), allows extended dosing interval due to its peculiar pharmacokinetics. Despite being registered for treatment of acute skin infections, off-label use has shown promise in various settings, particularly in osteo-articular infections. This study aims to assess dalbavancin's pharmacological efficacy and its safety and clinical success in patients treated according to personalized schedules guided by Therapeutic Drug Monitoring (TDM), particularly in long-term therapies.

Methods

non-interventional, retrospective, single-center pharmacological study. We included adult patients with at least one dalbavancin TDM determination from July 1, 2022 to February 1, 2024 and treated with outpatient parenteral antimicrobial therapy. We recorded dalbavancin trough concentration (Cmin) and its peak concentration (Cmax) and employed log-linear regression models to predict the timing of dalbavancin dosing, aiming to sustain Cmin levels above 4 or 8.04 mg/L, according to recent literature. Data regarding index infections, patients’ characteristics, outcomes, and adverse events were also collected.

Results

we included 32 patients, whose clinical and microbiological characteristics are depicted in Table 1. Regarding the primary outcome, 132/134 (98.5%) trough concentration was >4 mg/L, while 112/134 (83.6%) was >8.04 mg/L. For the secondary outcomes, 2/32 patients experienced an adverse event correlated to dalbavancin: (i) exanthema one week after the start of therapy and (ii) exanthema, conjunctivitis, angioedema, and nausea one month after the start of therapy. Moreover, we observed 4/32 clinical unsuccess (one failure during treatment, one relapse after the end of therapy, one switch to another antibiotic, and one isolation of non-susceptible microorganism).

Conclusions

a TDM-based approach with the use of a log-linear regression model allows a more precise timing of dalbavancin administration by maintaining sufficient concentration of circulating drugs. This approach is promising for infections requiring a long-term treatment, such as orthopedic infection where source control is not possible.

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TROUGH LEVELS OF DALBAVANCIN DURING LONG-TERM TREATMENT OF PERIPROSTHETIC JOINT INFECTIONS
Authors: Söderquist Bo , Möller Max , Salihovic Samira
Published: November 2024

Aim

Dalbavancin is a lipoglycopeptide with a broad antimicrobial spectrum against Gram-positive bacteria and effect against microorganisms in biofilm in vitro. Its pharmacokinetic properties, with an exceptionally long half-life of approximately 300 hours, allow for simplified administration that may be of value in the long-term treatment of bone and joint infections, such as prosthetic joint infections (PJIs). Several case reports and case series with “off-lable” treatment with dalbavancin of PJIs exist, but the optimal dosing regimen remains to be defined. Therapeutic drug monitoring (TDM) is recommended for treatment with >2 doses of dalbavancin. In the absence of TDM, the Swedish national guidelines for bone and joint infections (2023, www.infektion.net) recommends a loading dose of dalbavancin 1,500 mg on day 1 and 1,500 mg on days 8 – 14, after which from day 28 1,000 mg is given biweekly or 500 mg every week. The aim of the present study was to determine trough levels of dalbavancin in patients with long-term treatment of PJIs according to the national guidelines.

Method

Twelve patients with PJI were treated with at least 6 doses of dalbavancin, of which the first two doses were 1500 mg and the following doses were 1000 every second week, and prospectively sampled biweekly for determination of serum concentrations (trough levels) of dalbavancin which was measured by liquid chromatography coupled to electrospray tandem mass spectrometry (LC-MS/MS). The renal function was also examined.

Results

The median serum concentration 14 days after the first dose of dalbavancin 1500 mg was 36.3 mg/L (range 6.6 – 62.4 mg/L). The median value 14 days after the second dose of 1500 mg (day 27 – 28) was 48.2 mg/L (range 12.2 – 77.3 mg/L). The trough value after the last dose of a total of 6 – 7 doses was as median 43.1 mg/L (range 26.2 – 97.5 mg/L). Three patients showed a tendency towards successive accumulation of dalbavancin during treatment. None of the patients, including those three with increasing through levels during treatment, showed any significant alteration in creatinine nor glomerular filtration rate.

Conclusions

TDM during long-term treatment with dalbavancin is recommended to avoid the risk of accumulation and unnecessarily high trough values. With TDM, the dosing interval can be extended in several cases. In addition, with the support of TDM, subtherapeutic serum concentrations, with the risk of developing resistance, can be avoided.
THE IMPACT OF UNTOWARD EVENTS DURING PRIMARY OR REVISION TOTAL HIP OR KNEE ARTHROPLASTY SURGERY
Authors: Trebše Neža , Blas Mateja , Kanalec Tanja , Angelini Kristina , Filipič Tjaša , Levašic Vesna , Trebse Rihard
Published: November 2024

Aim

There is limited data on the frequency and impact of untoward events such as glove perforation, contamination of the surgical field (drape perforation, laceration, detachment), the unsterile object in the surgical field (hair, sweat droplet…), defecation, elevated air temperature…that may happen in the operating theatre. These events should influence the surgical site infection rate but it is not clear to what extent. We wanted to calculate the frequency and measure the impact of these events on the infection and general revision rate.

Method

In our institution, scrub nurses prospectively and diligently record untoward events in the theatres. We have an institutional implant registry with close to 100% data completion since 2001, and surgeons register complications before discharge. We analysed the respective databases and compared the revision and infection rate in the group with untoward events with the outcome of all arthroplasty patients within the same period. Two-tailed Z statistical test was used for analysis.

Results

Between 1.1.2012 and 31.12.2018 we operated 13574 prosthetic joints: 6232 primary THR (total hip replacement) and 5466 primary KR (total and partial knee replacement) and 1245 and 631 revisions respectively. During this period, we recorded 372 events (2.74%) including 20 (0.15 %) defecations, 40 (0.29 %) unsterile object in the surgical field, 73 (0.54%) field sterility violations, 45 (0.33 %) glove perforations, 45 (0.33 %) occasions with elevated air temperature, 106 (0.78%) with guests in the OR, 11 (0.08%) with wound near the surgical field, and 32 (0.24%) with other events. We followed the patients till 1.1.2022, in this time we recorded 27 (7.26%) reoperations in the cohort with untoward events. There were 9 (2.42%) infections and 18 (4.84%) aseptic revisions in the group with unwanted events.

The infection rate for all TJR (total joint replacement) from the period 2012-2018, followed till 1.1.2022 was 2.23%, the revision rate for any reason was 4.37%. For all THR (primary and revision) the infection rate was 0.84%, the overall revision rate was 3.18% and for the KR (primary and revision) 1.71% and 5,82% respectively. The difference is significant at p>0.05 for infection rate.

Conclusions

The potentially serious sterility disruptive events in the operative rooms did result in an increased infection rate but not an increase in revision rate. There is no data about the rate and the impact of these events besides for perforated surgical gloves with higher reported incidences than in our study influencing infection rate if perioperative antibiotic prophylaxis was not used. Ours is the first study reporting the impact of these unwanted events in the operating theatre.

Key words

orthopaedic surgery, unwanted events, revision rate
PREDICTING PERIPROSTHETIC JOINT INFECTION: EXTERNAL VALIDATION OF PREOPERATIVE PREDICTION MODELS
Authors: Yoon Seung-Jae , Jutte Paul , Soriano Alex , Sousa Ricardo , Zijlstra Wierd , Wouthuyzen-Bakker Marjan
Published: November 2024

Aim

This study aimed to externally validate promising preoperative PJI prediction models in a recent, multinational European cohort.

Method

Three preoperative PJI prediction models (by Tan et al., Del Toro et al., and Bülow et al.) which previously demonstrated high levels of accuracy were selected for validation. A multicenter retrospective observational analysis was performed of patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) between January 2020 and December 2021 and treated at centers in the Netherlands, Portugal, and Spain. Patient characteristics were compared between our cohort and those used to develop the prediction models. Model performance was assessed through discrimination and calibration.

Results

A total of 2684 patients were included of whom 60 developed a PJI (2.2%). Our patient cohort differed from the models’ original cohorts in terms of demographic variables, procedural variables, and the prevalence of comorbidities. The c-statistics for the Tan, Del Toro, and Bülow models were 0.72, 0.69, and 0.72 respectively. Calibration was reasonable, but precise percentage estimates for PJI risk were most accurate for predicted risks up to 3-4%; the Tan model overestimated risks above 4%, while the Del Toro model underestimated risks above 3%.

Conclusions

In this multinational cohort study, the Tan, Del Toro, and Bülow PJI prediction models were found to be externally valid for classifying high risk patients for developing a PJI. These models hold promise for clinical application to enhance preoperative patient counseling and targeted prevention strategies.

Keywords

Periprosthetic Joint Infection (PJI), High Risk Groups, Prediction Models, Validation, Infection Prevention
PRE-TREATING PJI WITH SYSTEMIC ANTIBIOTICS DECREASES TISSUE AND IMPLANT BACTERIAL COUNTS: RESULTS FROM AN IN VIVO MODEL
Authors: Chao Christina , Khilnani Tyler , Jo Suenghwan , Yang Xu , Bostrom Mathias , Carli Alberto
Published: November 2024

Aim

Periprosthetic joint infection (PJI) is a complication of total joint arthroplasty that typically requires revision surgery for treatment. Systemic antibiotics are usually held prior to surgery to improve yield of intraoperative cultures. However, recent studies suggest that preoperative aspirations have a high concordance with intraoperative cultures, which may allow surgeons to initiate antibiotic treatment earlier. The purpose of the study was to investigate the effect of Pre-surgical systemic antibiotic therapy on the bacterial burden within the periprosthetic space and systemic immune reaction.

Method

PJI was induced with MSSA (Xen36) S. aureus in the right knee of 16-week old, female, C57BL6 mice using a previously validated murine model. Mice were randomized to three groups (n=8, each): control; Vanc, receiving systemic vancomycin (110mg/kg, SQ, twice daily); or VancRif receiving vancomycin same as in Vanc group, plus rifampin (12mg/kg dose, IV, once daily). Following 2 weeks of treatment, mice were euthanized and periprosthetic bone, soft tissue and the implant were harvested. Bacterial burden, colony forming units (CFUs), was quantified in soft tissue, tibial bone, and on the implant. Specifically, tissues were homogenized and serially plated for CFUs, while the implant was sonicated and then plated for CFUs. The host immune response was analysed through weighing inguinal and iliac lymph nodes and through measuring serum amyloid A (SAA). Non-parametric pairwise group comparisons of the three outcome measures were performed using a Mann-Whitney U test.

Results

VancRif, the combined treatment significantly reduced bacterial burden in the periprosthetic soft tissue, bone, and implant compared to control (p<0.001) and Vanc alone (p<0.001). While not significant, Vanc alone did reduce bacterial load as compared to control. The ipsilateral weight of the iliac lymph nodes was significantly reduced in Vanc and VancRif mice compared to controls (p<0.001), was well as in VancRif versus Vanc alone (p<0.001). Interestingly, SAA levels did not significantly differ among all groups. During tissue harvesting, minimal purulence was observed in antibiotic treatment groups, unlike controls.

Conclusions

Treating active PJI with vancomycin alone decreases periprosthetic bacterial loads and reduces the local immunological response. This effect is significantly enhanced with the combined rifampin use. These findings could suggest that when culture positive PJI is diagnosed, pre-surgical treatment with antibiotics may decrease immunosuppression and soft tissue infiltration, leading to a better chance of infection cure with subsequent surgical debridement. Histological investigations and repeat experiments involving subsequent surgical treatment are underway.

Acknowledgements

Funding comes from internal institutional grants.
THE VALUE OF SYNOVIAL CALPROTECTIN IN THE DIAGNOSIS OF PERIPROSTHETIC JOINT INFECTION AFTER HIP AND KNEE ARTHROPLASTY
Authors: Bekkers Wouter , Zwart Vivian , Swietoslawki Adam , Oost Iris Koenraadt-van , Nijs Anouk , Emmen Judith , Van Geenen Rutger
Published: November 2024

Aim

Periprosthetic joint infection (PJI) is one of the main reasons for revision surgery after primary unicompartmental knee arthroplasty (UKA), total knee arthroplasty (TKA) or total hip arthroplasty (THA). Currently the MSIS and EBJIS criteria sets are considered to be the gold standards in determining PJI. These criteria sets are complex and contain tests that are time-consuming and many are rather costly. Therefore, further research is indicated to find a simpler but equally reliable diagnostic test. In this study we evaluated the additional value of calprotectine measurement in synovial fluid in patients undergoing hip and knee (revision) arthroplasty following routine work-up.

Method

In a retrospective cohort study, we analyzed 182 synovial fluid samples from 143 patients with suspected PJI after UKA, TKA, THA or revision arthroplasty. Twenty-six of those cases were classified as PJI according to the MSIS and EBJIS criteria. Subsequently, synovial calprotectin was determined, using a lateral flow assay and two cut-off thresholds of ≥14 mg/L and ≥50 mg/L. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of synovial calprotectin was determined.

Results

When applying the MSIS and EBJIS criteria and a calprotectin level ≥14 mg/L, synovial calprotectin revealed an area under the curve of 0.96 (95% CI 0.90-1.00), with 92.3% sensitivity and 100% specificity. The PPV and NPV were 100% and 92.9% respectively. When applying the MSIS and EBJIS criteria and a calprotectin level ≥ 50 mg/L, synovial calprotectin revealed an area under the curve of 0.94 (95% CI 0.87-1.00), with 88.5% sensitivity and 100% specificity. The PPV and NPV were 100% and 89.7% respectively.

Conclusions

The value of calprotectin in synovial fluid gives valuable information with a single test result, resulting in high predictive value in the diagnosis of PJI after hip or knee arthroplasty and should seriously be considered as part of PJI diagnostics in an outpatient clinical setting. The high specificity can help rule in patients that are suspected of PJI. Therefor this test can be helpful in a preop diagnostic work-up to avoid unnecessary revisions in patients with well-placed and well-fixed arthroplasties with a suspected PJI. These conclusions are independent of which criteria set was used as a gold standard.
CAN THE USE OF A SYNTHETIC SYNOVIAL FLUID MEDIUM IN COMBINATION WITH ISOTHERMAL MICROCALORIMETRY IMPROVE ACCURACY AND REDUCE TIME TO DETECTION IN PERIPROSTHETIC JOINT INFECTIONS?
Authors: De Bleeckere Amber , Neyt Jeroen , Vandendriessche Stien , Boelens Jerina , Coenye Tom
Published: November 2024

Aim

Fast and accurate identification of pathogens causing periprosthetic joint infections (PJI) is essential to initiate effective antimicrobial treatment. Culture-based approaches frequently yield false negative results, despite clear signs of infection. This may be due to the use of general growth media, which do not mimic the conditions at site of infection. Possible alternative approaches include DNA-based techniques, the use of in vivo-like media and isothermal microcalorimetry (ITC). We developed a synthetic synovial fluid (SSF) medium that closely resembles the in vivo microenvironment and allows to grow and study PJI pathogens in physiologically relevant conditions. In this study we investigated whether the use of ITC in combination with the SSF medium can improve accuracy and time to detection in the context of PJI.

Methods

In this study, 120 synovial fluid samples were included, aspirated from patients with clinical signs of PJI. For these samples microbiology data (obtained in the clinical microbiology lab using standard procedures) and next generation sequencing (NGS) data, were available. The samples were incubated in the SSF medium at different oxygen levels (21% O2, 3% O2 and 0% O2) for 10 days. Every 24h, the presence of growth was checked. From positive samples, cultures were purified on Columbia blood agar and identified using MALDI-TOF. In parallel, heat produced by metabolically active microorganisms present in the samples was measured using ITC (calScreener, Symcel), (96h at 37°C, in SSF, BHI and thioglycolate). From the resulting thermograms the ‘time to activity’ could be derived. The accuracy and time to detection were compared between the different detection methods.

Results

So far, seven samples were investigated. Using conventional culture-based techniques only 14.3% of the samples resulted in positive cultures, whereas NGS indicated the presence of microorganisms in 57.1% of the samples (with 3/7 samples being polymicrobial). Strikingly, 100% of the samples resulted in positive cultures after incubation in the SSF medium, with time to detection varying from 1 to 9 days. MALDI-TOF revealed all samples to be polymicrobial after cultivation in SSF, identifying organisms not detected by conventional techniques or NGS. For the samples investigated so far, signals obtained with ITC were low, probably reflecting the low microbial load in the first set of samples.

Conclusion

These initial results highlight the potential of the SSF medium as an alternative culture medium to detect microorganisms in PJI context. Further studies with additional samples are ongoing; in addition, the microcalorimetry workflow is being optimized.
COMPARISON OF SYNOVIAL CALPROTECTIN AND ALPHA-DEFENSIN FOR THE DIAGNOSIS OF PERSISTENT PERIPROSTHETIC JOINT INFECTION AT THE SECOND STAGE OF A TWO-STAGE REVISION ARTHROPLASTY
Authors: Mitterer Jennyfer A , Hartmann Susana Gardete , Simon Sebastian , Sebastian Sujeesh , Chlud Leonie , Hofstaetter Jochen G
Published: November 2024

Background

Two-stage revision arthroplasty is the standard treatment for chronic hip and knee periprosthetic joint infections (PJI). Accurate diagnosis of persistent infections at 2nd stage using established biomarkers and diagnostic criteria is of paramount importance. This study aimed to evaluate the diagnostic value of synovial calprotectin and alpha-defensin, and compare established diagnostic criteria from the International Consensus Meeting (ICM 2018) and the European Bone and Joint Infection Society (EBJIS 2021) to determine persistent PJI at the 2nd stage of a two-stage revision arthroplasty.

Methods

We retrospectively analyzed 97 patients who underwent 100 two-stage revisions (hip: 39, knee: 61). Synovial fluid samples were assessed for calprotectin and alpha-defensin levels. ICM 2018 and EBJIS 2021 were applied to all patients undergoing 2nd stage revision. Receiver operating characteristic (ROC) curves and Youden Index were utilized to determine optimal cut-off values, and correlations between biomarkers were evaluated. The microbiological spectrum was analyzed at 2nd stage and re-revision surgery.

Results

Calprotectin levels showed a sensitivity of 66.7%, specificity of 32.9%, and accuracy of 38.0% in predicting septic failure. Alpha-defensin showed sensitivity of 28.6%, specificity of 87.8%, and accuracy of 79.2%. Significant correlations included: calprotectin with PMN% (r = 0.471, p = 0.05) and alpha-defensin with WBC (r = 0.830, p < 0.01) in the successful cohort. For septic re-revisions, calprotectin and alpha-defensin were highly correlated (r = 0.969, p < 0.01). ICM correctly diagnosed persistent PJI in 26.7%, while EBJIS diagnosed 24.2%. The microbial spectrum shifted from gram-positive to gram-negative bacteria between reimplantation and re-revision surgeries.

Conclusion

Synovial calprotectin and alpha-defensin demonstrated limited accuracy in ruling out persistent PJI at reimplantation. The low sensitivity of current diagnostic criteria, combined with the observed shift in microbial spectrum, underscores the challenges in diagnosing persistent PJI during 2nd stage of a two-stage revisions arthroplasty.
NEUTROPHIL EXTRACELLULAR TRAP-RELATED BIOMARKERS ARE INCREASED IN SYNOVIAL FLUID OF PATIENTS WITH PERIPROSTHETIC JOINT INFECTION
Authors: Kimura Osamu , Mozella Alan , Cobra Hugo , Saraiva Augusto , Leal Ana Carolina
Published: November 2024

Aim

Evaluate if Neutrophil Extracellular Traps related biomarkers (citrullinated histone H3 [H3Cit], cellfree DNA [cfDNA], and myeloperoxidase) are increased in synovial fluid of patients with PJI and investigate the diagnostic accuracy of NET formation biomarkers for PJI.

Method

Patients who underwent hip or knee revision total joint arthroplasty were categorised into two groups according to the Second International Consensus Meeting on Musculoskeletal Infection (2018) criteria. Sixteen patients were classified as infected and 16 as non-infected. cf-DNA, myeloperoxidase and H3Cit were measured in synovial fluid collected during surgery. Sensitivity, specificity, and receiver operating characteristic (ROC) curve were calculated.

Results

Patients with PJI presented significantly higher levels of synovial fluid cf-DNA (105.5 ng/ml ± 58.3 vs 1.9 ± 1.2, p>0.0001), myeloperoxidase (1575 pg/ml ± 826 vs 50.16 ± 100, p<0.0001) and citrullinated histone H3 (1.688 ± 1.214 vs 13.88 ± 24.4, p < 0.0001). In the ROC curve analyses, the area under the curve for cf-DNA, myeloperoxidase and H3cit were 1 [0.89 – 1], 0.98 [0.86 – 1], and 0.94 [0.8 – 0.99], respectively. The sensitivity for detecting PJI using synovial fluid was 100% for cf-DNA, 93,7% for myeloperoxidase, and 87,5% for H3cit. The sensitivity for cf-DNA and myeloperoxidase was 100%, and 87,5 % for H3cit.

Conclusions

Our results show that neutrophils within periprosthetic microenvironment release NETs as part of the bactericidal arsenal to fight infection. These results allow a better understanding of the cellular and molecular processes that occur in this microenvironment, enabling the design of more assertive strategies for the identification of new biomarkers and for a better use of the available ones. Furthermore, novel studies are needed to define whether and how NET-related biomarkers can be useful for the diagnosis of PJI.
INTERNATIONAL PRACTICE VARIATION OF SUPPRESSIVE ANTIMICROBIAL TREATMENT FOR PERIPROSTHETIC JOINT INFECTION: A GLOBAL SURVEY STUDY
Authors: Hanssen Jaap , Gademan Maaike , Wouthuyzen-Bakker Marjan , Davis Joshua Saul , Dewar David , Manning Laurens , Campbell David , van Prehn Joffrey , Miller Andy , van der Wal Robert , van der Linden Enrike , Cortes-Penfield Nicolas , Soriano Alex , De Boer Mark G.J. , Scheper Henk
Published: November 2024

Aim

Suppressive antimicrobial therapy (SAT) is used worldwide for patients with a prosthetic joint infection (PJI but clear definitions or guidelines regarding the indications, antimicrobial strategy or treatment duration are currently lacking in the literature. The aim of this study was to identify the global differences in the clinical practice of SAT for PJI.

Method

An online survey was designed to investigate the current opinion on indication and treatment goals, preferred antimicrobial drugs, dosing and treatment duration and follow-up of patients with PJI on suppression. The survey was distributed using e-mail lists of several international bone and joint infection societies and study groups. Recipients were asked to share the survey with colleagues who were not a member of one of the societies but who were involved in PJI care.

Results

The questionnaire was fully completed by 330 physicians from 43 different countries on six continents (Europe, n=134, 41%; Oceania n=112, 34%; North America, n=51, 16%; other, n=33, 10%; total response rate 14%). Antimicrobial treatment for PJI was discussed in a multidisciplinary team in Europe (90%), Oceania (42%) and North America (12%). In six of eight (75%) different clinical scenarios, respondents from North America would most often place a patient on SAT. In seven of eight (88%) scenarios, SAT was started least often by European respondents. The presence of a fistula was considered a contra-indication for suppression by 74 respondents (22%). First choices of SAT for staphylococcal PJI were: oral cephalosporins (39%) and tetracyclines (31%) in North America; anti-staphylococcal penicillins (55%) and oral cephalosporins (24%) in Oceania; tetracyclines (27%) and anti-staphylococcal penicillins (22%) in Europe. For streptococcal PJI, most clinicians preferred penicillins (91% in Oceania, 67% in Europe, and 53% in North America). Preferred SAT for gram negative PJI was: fluoroquinolones and a penicillin/betalactamase inhibitor in North America (26% and 18%, respectively) and Oceania (23% and 27%, respectively); fluoroquinolones (31%) and Cotrimoxazole (28%) in Europe. The dosage of SAT was never lowered (n=126, 38%), standardly lowered for all antibiotics (n=79, 24%) or only lowered for specific antibiotics (n=125, 38%). SAT was prescribed for an indefinite duration (n=43, 13%), as fixed duration between six months and three years (n=104, 32%) or for an undetermined prespecified duration (n=154, 47%).

Conclusions

Substantial variation in the practice of SAT for PJI exists between physicians worldwide and throughout the different continents. This reflects the paucity of data regarding the indication and treatment of PJI with SAT.
ULTRATHIN SILVER-POLYSILOXANE-COATED PLATES FOR REVISION OF INFECTED FEMORAL NONUNION: FIRST RESULTS
Authors: Mueller Maximilian M. , Kowald Birgitt , Gerlach Ulf-Joachim , Grimme Cornelius , Schulz Arndt-Peter , Frosch Karl-Heinz , Schoop-Schmetgens Rita
Published: November 2024

Aim

Aim of this study was to establish the first clinical results after implantation of ultrathin silver-polysiloxane-coated1 plates in the treatment of infected non-union of the femoral shaft.

Method

As part of the REFECT study, a prospective, non-interventional analysis was conducted encompassing all patients who received internal stabilization with a silver-coated1 plate from 01/2023 to 09/2024 as part of the treatment for infected non-union of the femur. Standardized clinical follow-ups including PROMs (WOMAC-Index, LEF-S, EQ-5D, VAS) and X-rays were performed 3, 6, 12 (and 24) months postoperatively.

For comparison, a retrospective analysis of 76 patients with infected femoral non-union, who had received a stabilization with an uncoated plate in the past 10 years, was performed.

Results

The mean follow-up of the 8 included patients (mean bone defect: 3.6 cm) was 9 months (as of 04/24). Multiresistant bacteria were found in the intraoperative samples of 5 patients. The concentration of silver ions in blood serum reached a maximum of 0.014 mg/l in the laboratory controls. All patients showed a positive healing process with no sign of re-infection and no adverse procedure-associated events. Full weight bearing was achieved after an average of 4 months (n=6) with improved WOMAC-, LEF-S-, EQ-5D and VAS-score at 1-year FU. In the reference group (uncoated, mean FU: 3.5 years), there was a re-infection rate of 25 %, mostly in the first 2 years. Difficult-to-treat bacteria were detected in 22%, multiresistant Staph. epidermidis in 28% of cases.

Conclusions

The silver-coated1 implants showed good biocompatibility with no evidence of procedure-associated complications.

The use of silver-coated1 implants could reduce the risk of re-infection.

Further clinical data with longer follow-up are needed to assess the long-term value of the procedure.
EVALUATION OF A NEW POINT-OF-CARE APPROACH FOR SYNOVIAL FLUID CELL-FREE DNA QUANTIFICATION FOR PERIPROSTHETIC JOINT INFECTION DIAGNOSIS
Authors: Cobra Hugo , Mozella Alan , Leal Ana Carolina
Published: November 2024

Aim

Periprosthetic joint infection (PJI) is one of the most frequent and devastating complications of total knee arthroplasty (TKA). Accurate diagnosis and proper treatment are essential to prevent functional loss and progression to systemic infection. However, the correct diagnosis of PJI is still a challenge since there is no accurate diagnostic method and the existing diagnostic criteria are based on serological, histological and microbiological tests that are imprecise and time-consuming. Recently, it was demonstrated that cell-free DNA is increased in the synovial fluid of patients with PJI. Therefore, this study aims to evaluate a new point-of-care methodology for quantifying free DNA in synovial fluid.

Method

A prospective study was carried out with patients undergoing TKA revision surgery, from whom it was possible to collect synovial fluid (SF) during the surgical procedure. Cell-free DNA quantification was performed directly from the SF, using a portable fluorimeter. Sensitivity, specificity and receiver operating characteristic (ROC) curve were calculated.

Results

Fifty-four patients were included in the study, of which 25 were diagnosed with PJI. Cell-free DNA levels measured immediately after collection were increased in the synovial fluid of patients with PJI (26.3 ± 14.8) in comparison with the uninfected group (4.6 ng/ml ± 3.8, p< 0.0001). The area under the receiver operating characteristic curve (AUC ROC) was 0.981 (95% CI 0.914 to 0.999).

Conclusions

From the results presented, we can conclude that the quantification of free DNA with a portable fluorimeter proved to be a test with high sensitivity and specificity for the diagnosis of PJI.
16S RRNA V3-V4 AMPLICON NEXT-GENERATION SEQUENCING IN THE DIAGNOSIS OF PERIPROSTHETIC JOINT INFECTIONS
Authors: Erbeznik Anja , Šturm Andraž Celar , Smrdel Katja Strašek , Triglav Tina , Kocjancic Boštjan , Pompe Borut , Dolinar Drago , Mavcic Blaz , Mercun Aljaz , Kolar Matic , Avsec Klemen , Papst Lea , Vodicar Polona Maver
Published: November 2024

Aim

To date, no ultimate diagnostic gold standard for prosthetic joint infections (PJI) has been established. In recent years, next generation sequencing (NGS) has emerged as a promising new tool, especially in culture-negative samples. In this prospective study, we performed metagenomic analysis using 16S rRNA V3-V4 amplicon NGS in samples from patients with suspected PJI.

Methods

A total of 257 (187 culture-negative (CN) and 70 culture-positive (CP)) prospectively collected tissues and sonication fluid from 32 patients (56 revisions) were included. 16S rRNA V3-V4 amplicons were sequenced using Illumina's MiSeq (California, USA) followed by bioinformatic analysis using nf-core/ampliseq pipeline.

Results

We successfully sequenced 255 samples and detected a total of 105 microorganisms. These were mainly environmental microorganisms present in a small number of reads (≤100), indicating possible contamination. Pseudomonas spp. (non-aeruginosa species) was detected most frequently in 73% (187/255) of samples. The test showed limitations in species classification and identified microorganisms mainly at genus level. Significant differences in the number of reads were observed when comparing CN (≤100) and CP (≥1000) samples. In two CP, no bacteria were identified with sequencing, which is probably due to low bacterial load (1 CFU. Haemophilus spp. was detected with a significant number of reads (≥10000) in five samples from a single patient, in whom infection was considered likely according to EBJIS criteria, changing it to confirmed infection. Staphylococcus spp. was identified with ≥10000 reads in two CNs from an individual who was receiving antibiotic treatment at the time, had clinical signs of infection, and had a confirmed infection with S. lugdunensis one month earlier. Cutibacterium spp. with 36% (93/257) and Staphylococcus spp. with 34% (87/257) were detected with a minimal number of reads (≤100) in several CN, indicating possible contamination with normal skin microbiota. In one patient, Facklamia spp., an opportunistic pathogen, was detected in two samples by sequencing, but not by culture.

Conclusions

We consider 16S rRNA V3-V4 amplicon sequencing to be a promising tool; however, further studies are needed to clarify uncertainties regarding the interpretation of the results in combination with other criteria. Using this method, we were able to successfully confirm infection in two patients whose microbiological results were initially negative, leading to a change from likely to confirmed infection in one case. The thresholds and interpretation of the results are currently unclear, therefore the method is being used experimentally rather than diagnostically at the time of writing.