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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 12 - 12
22 Nov 2024
Wang L Trampuz A Zhang X
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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.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 2 - 2
22 Nov 2024
Roskar S Faganeli N Mihalic R Trebse R
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Aim

Arthroscopic interventions have revolutionized the treatment of joint pathologies. The appropriate diagnostics and treatment are required for infections after ligament reconstructions using non-resorbable material such as tendon grafts, anchors, and sutures, prone to biofilm formation. The infection rate is around 1% for knee and shoulder, while up to 4% for Achilles tendon reconstructions. Despite high number of these procedures worldwide, there is limited evidence about the best treatment protocol. Our study aimed to provide a general protocol for the treatment of small implants for soft tissue reconstruction.

Method

Between 2019 and 2023, we treated 48 infections of ligament, meniscus, and tendon reconstructions out of 7291 related procedures performed in the same time period. Early infection (<30 days) were treated with an arthroscopic debridement and implant retention (DAIR), except Achilles tendons had open DAIR, while those with delayed or chronic infection (>30 days) were treated with extensive debridement and lavage combined with one-stage exchange (OSE) or implant removal. During surgery, at least 5 microbiological s and samples for histopathology were obtained. The removed material was sonicated. After surgery, all patients were one week on iv. antibiotics, followed by oral antibiofilm antibiotics for 6 weeks including rifampicin and/or a quinolone. All patients were followed for at least 1 year. Failure was defined as the need for additional revision surgery after finished iv. antibiotic treatment.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 23 - 23
22 Nov 2024
Cojutti PG Tedeschi S Zamparini E Fornaro G Malerba F Zagarrigo M Sambri A De Paolis M Viale P Pea F
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Aim

Daptomycin plus fosfomycin combination therapy is a valuable strategy for treating staphylococcal osteoarticular infections. Considernig that each gram of fosfomycin contains 330 mg of sodium, electrolytic imbalance due to sodium overload could pose safety issues, especially in the cardiopatic patients and/or in the frail elderly. The aim of this study was to compare the efficacy of using reduced vs. standard daily dose fosfomycin in combination with daptomycin in a cohort of patients with osteoarticular infections.

Method

This analysis included adult patients with osteoarticular infections admitted to the Infectious Diseases Unit of our University hospital in the period Nov 2022 – Feb 2024 and who were treated with daptomycin (8-10 mg/kg/daily) plus 24h-continuous infusion (CI) fosfomycin at the standard-dose of 16 g daily (standard-dose group) or at the reduced-dose of 8-12 g daily (reduced-dose group). All the patients underwent therapeutic drug monitoring (TDM) of fosfomycin for granting a pharmacodynamic target attainment of 24h-area under the concentration-time curve over minimum inhibitory concentration (AUC24h/MIC) >95 against Staphylococcus aureus with an MIC value up to 32 mg/L and of 70%t>MIC. Estimated glomerular filtration rate (eGFR) was assessed at each TDM session. Patient clinical outcome was assessed.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 73 - 73
22 Nov 2024
Erbeznik A Smrdel KS Kišek TC Cvitković-Špik V Triglav T Vodicar PM
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Aim

The aim of this study was to develop an in-house multiplex PCR real-time assay on the LightCycler 480 system (Roche, Basel, Switzerland) with the aim of rapid detection of common pathogens in prosthetic joint infections (PJI), followed by validation on clinical samples (sonication fluid and tissue biopsies) routinely collected for PJI diagnosis.

Methods

Using the PrimerQuest and CLC WorkBench tool, we designed six primer sets with specific fluorescently labelled TaqMan probes for the nuc gene in different Staphylococcus species (S. aureus, S. epidermidis, S. capitis, S. lugdunensis, S. hominis, S. haemolyticus). In addition, primers previously developed by Renz et al. (2022) for C. acnes were integrated into our assay with internal control of isolation, leading to the development of specific mPCR assay with seven included targets. Analytical sensitivity and specificity were evaluated using reference bacterial strains. To determine the assay's limit of detection (LOD), we conducted serial dilutions of eluates containing known concentrations of bacterial DNA copies/µl. The overall LOD in spiked clinical samples, including sample preparation and DNA isolation on MagnaPure24, was measured through 10-fold serial dilutions (from 109 to 10-1 CFU/ml) including additional dilutions of 5000, 500, 50 and 5 CFU/ml.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 10 - 10
22 Nov 2024
Frank F Hotchen A Valand P Stubbs D Ferguson J McNally M
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Aim

This retrospective study evaluated the outcome of treatment for unhealed fracture-related infections (FRI).

Methods

We identified a consecutive, single-centre cohort of patients having treatment for an FRI Consensus confirmed FRI. All fractures were unhealed at the time of treatment. Patients were followed up for at least one year. Successful outcome was a healed fracture without recurrent infection. Lack of union, persistent infection and/or unplanned reoperation defined failure.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 77 - 77
22 Nov 2024
Vidal LS Auñon A García AB Cañete JG Parron R Esteban-Moreno J
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Aim

To evaluate the bacterial counts of sonicatied implants in patients with osteoarticular infections. Various studies have demostrated the usefulness of sonication of retrieved implants in order to provide an accurate microbiological diagnosis. Although cutoff values for original sonicate counts have been established, the use of centrifugation may influence these values

Method

A retrospective, single-center study, including sonication fluid samples from implants removed between January 2011 and October 2023, was performed. Patients were diagnosed with implant-associated infection based on the criteria available at the time of diagnosis. Osteoarticular implants were sonicated following the protocol described by Esteban et al. Sonicated fluid was centrifuged for 20 minutes at 3000 x g, and the sediment was resuspended in 5 mL of phosphate buffer solution. Ten µl of the sample were streaked onto each medium for quantitative culture. Bacterial counts exceeding 100,000 CFU/mL were considered as 100,000 CFU/mL for statistical analysis.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 33 - 33
22 Nov 2024
Kristensen N Manning L Lange J Davis J
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Aim

Periprosthetic Joint Infection (PJI) is a devastating complication in hip and knee joint arthroplasty. The “JS BACH” classification system was developed in 2021 to stratify the complexity of PJI, and more importantly, to act as a tool to guide referrals to specialist centers. The “JS BACH” classification has not been validated in an external cohort. This study aimed to do so using a large prospective cohort from Australia and New Zealand.

Method

We applied the JS-BACH classification to the Prosthetic Joint Infection in Australia and New Zealand Observational (PIANO) cohort. This prospective study of newly diagnosed PJI collected 2-year outcome data from 653 participants enrolled in 27 hospitals. The definition of PJI treatment failure at 24 months was any of the following: death, clinical or microbiological signs of infection, destination prosthesis removed, or ongoing antibiotic use.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 44 - 44
22 Nov 2024
De Bleeckere A Neyt J Vandendriessche S Boelens J Coenye T
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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.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 70 - 70
22 Nov 2024
Jacob A Onsea J Bessems L Spoormans P Vles G Metsemakers W Depypere M
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Aim

The primary objective is to evaluate the diagnostic performance of inoculating homogenized tissue and bone biopsies in blood culture bottles (BCB) for patients with (suspected) orthopaedic device-related infections. As secondary objective the time to positivity (TTP) of BCB and Wilkins-Chalgren broth (conventional method) will be evaluated.

Method

Patients undergoing revision surgery due to suspected or proven fracture-related infection (FRI) or periprosthetic joint infection (PJI) according to respectively Consensus definition and EBJIS definition are included.1,2 A minimal of three macroscopic infected/inflamed tissue/bone samples are collected in a container with saline and glass beads. 1.5 mL of the homogenized suspension is inoculated in BacT/ALERT FA and FN Plus bottles for 14 days. The remaining suspension is inoculated in Wilkins-Chalgren broth for 10 days and subcultured when cloudy or after 10 days. TTP is defined as the time until definite identification of the pathogen in the Laboratory Information System.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 15 - 15
22 Nov 2024
Liew-Littorin C Davidsson S Nilsdotter-Augustinsson Å Brueggemann H Söderquist B
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Aim

Cutibacterium acnes is a major skin commensal that may also act as an opportunistic pathogen. Findings of C. acnes in tissue cultures obtained during arthroplasty revision surgery are difficult to interpret, since they may represent true infection or contamination. This study investigated whether C. acnes isolates obtained from prosthetic joint infections (PJIs) were related and shared common genomic traits that might correlate with clinical courses and patient outcomes.

Method

C. acnes isolates from revision surgery of patients with PJIs of the hip, shoulder, and knee were characterized using molecular methods to determine sequence type (ST) and the presence of virulence determinants (CAMP factors, dermatan sulfate-binding adhesion 1, hyaluronidase lyase, and linear plasmid). A standardized review of the patients’ medical charts was performed.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 81 - 81
22 Nov 2024
de Waard G Veltman W van Oldenrijk J Bos K Koch B
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Aim

Prosthetic joint infections (PJI) are a common reason for revisions in patients that underwent total arthroplasty of the hip (THA) or knee (TKA). Extensive antibiotic treatment follows while a clear understanding of target site concentrations is lacking. The aim is to investigate the target site concentrations, like bone and synovial tissue concentrations, which consequently may lead to an optimisation of the dosing regiments of cefuroxime of PJI patients suffering from pain and immobility. Dosing optimisation may lead to a reduced risk of (re-)infection and adverse effects like renal-insufficiency and therefore lower health-care costs.

Method

Patients (n=26) with PJI of hip or knee undergoing a one- or two-stage revision treated with cefuroxime were included as part of the ASTERICS study. During implant removal two samples were collected 15-30 and 60-120 minutes after IV infusion of plasma, bone tissue and synovial tissue and one synovial fluid sample. Samples were analysed using a UltraPerformance Convergence Chromotography – quadruple mass spectrometry system (UPC2-MS/MS). Bone tissue and synovial tissue were pulverized before analysis acquiring for bone tissue a homogenate of cortical and cancellous bone. Using nonlinear mixed effect modelling (NONMEM) a base model was developed to analyse the bone to plasma ratio of cefuroxime in osteomyelitis patients.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 79 - 79
22 Nov 2024
Luger M Böhler C Staats K Windhager R Sigmund IK
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Aim

Diagnosing low-grade periprosthetic joint infections (PJI) can be very challenging due to low-virulent microorganisms capable of forming biofilm. Clinical signs can be subtle and may be similar to those of aseptic failure. To minimize morbidity and mortality and to preserve quality of life, accurate diagnosis is essential. The aim of this study was to assess the performance of various diagnostic tests in diagnosing low-grade PJI.

Methods

Patients undergoing revision surgery after total hip and knee arthroplasty were included in this retrospective cohort study. A standardized diagnostic workup was performed using the components of the 2021 European Bone and Joint Infection Society (EBJIS) definition of PJI. For statistical analyses, the respective test was excluded from the infection definition to eliminate incorporation bias. Receiver-operating-characteristic curves were used to calculate the diagnostic performance of each test, and their area-under-the-curves (AUC) were compared using the z-test.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 75 - 75
22 Nov 2024
Erbeznik A Šturm AC Smrdel KS Triglav T Cvitković-Špik V Kišek TC Kocjancic B Pompe B Dolinar D Mavcic B Mercun A Kolar M Avsec K Papst L Vodicar PM
Full Access

Aim

We prospectively evaluated four different microbiological tools for diagnostics of prosthetic joint infections (PJI), and assessed their impact on the categorization of infection according to EBJIS guidelines. We compared culture, in-house real-time mPCR for S. aureus, S. lugdunensis, S. hominis, S. epidermidis, S. capitis, S. haemolyticus, C. acnes (mPCR), broad-spectrum PCR (Molzym) with 16S rRNA V3-V4 amplicon Sanger sequencing (16S PCR), and 16S rRNA V3-V4 amplicon next-generation sequencing (16S NGS) on MiSeq (Ilumina).

Methods

A total of 341 samples (sonication fluid, tissue biopsy, synovial fluid) were collected from 32 patients with suspected PJI who underwent 56 revision surgeries at the Orthopaedic Centre University Hospital Ljubljana, between 2022 and 2024. Samples were processed using standard protocols for routine culture, followed by DNA isolation using the MagnaPure24 (Roche). All samples were tested with mPCR, and an additional ≥4 samples from each revision (244 in total) were subjected to further metagenomic analysis. Culture results were considered positive if the same microorganism was detected in ≥2 samples, ≥50 CFU/ml were present in the sonication fluid, or ≥1 sample was positive for a more virulent microorganism or if the patient had received antibiotic treatment.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 18 - 18
22 Nov 2024
Gupta V Shahban S Petrie M Kimani P Kozdryk J Riemer B King R Westerman R Foguet P
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Aim

Predicting success of a Debridement, Antibiotics and Implant Retention (DAIR) procedure for Periprosthetic Joint Infection (PJI) remains a challenge. A failed DAIR might adversely affect the outcome of any future revision surgery for PJI. Hence, the ability to identify and optimise factors predictive of DAIR success would help target the procedure to the appropriate patient cohort and avoid unnecessary surgery for patients where a DAIR is unlikely to eradicate infection.

Method

A retrospective review of our prospective Bone Infection Group database was performed to identify all patients who underwent a DAIR of their hip or knee arthroplasty. Diagnosis of PJI was confirmed using the Musculoskeletal Infection Society (MSIS) 2013 and the European Bone and Joint Infection Society (EBJIS) 2021 classification systems. DAIR surgery was grouped into “successful” or “unsuccessful” outcomes as per the MSIS working group outcome-reporting tool.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 34 - 34
22 Nov 2024
Seixas J Altoé LS Santos AC Ribau A Abreu M Carvalho A Pereira F Soares D Sousa R
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Aim

Determine therapeutic and prognostic value of three different prosthetic joint infections (PJI) staging systems – JS-Bach, McPherson and PJI-TNM.

Method

Retrospective analysis of patients who received surgery for PJI between 2011 and 2022 at one single institution, including DAIR, 1-stage revision and 2-stage revision. We applied three staging systems - JS-Bach, McPherson, PJI-TNM – and categorize the results into A (less severe), B (intermediate) and C (most severe). Demographic data and comorbidities, anatomic location, type of treatment, recurrency of infection, final outcome and antibiogram were analyzed.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 74 - 74
22 Nov 2024
Erbeznik A Šturm AC Smrdel KS Triglav T Kocjancic B Pompe B Dolinar D Mavcic B Mercun A Kolar M Avsec K Papst L Vodicar PM
Full Access

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.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 67 - 67
22 Nov 2024
Youf R Ruth S Mannala G Zhao Y Alt V Riool M
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Aim

In trauma surgery, the development of biomaterial-associated infections (BAI) is one of the most common complications affecting trauma patients, requiring prolonged hospitalization and the intensive use of antibiotics. Following the attachment of bacteria on the surface of the biomaterial, the biofilm-forming bacteria could initiate a chronic implant-related infection. Despite the use of conventional local and systemic antibiotic therapies, persistent biofilms involve various resistance mechanisms that contribute to therapeutic failures. The development of in vivo chronic BAI models to optimize antibiofilm treatments is a major challenge. Indeed, the biofilm pathogenicity and the host response need to be finely regulated, and compatible with the animal lifestyle. Previously, a Galleria mellonella larvae model for the formation of an early-stage biofilm on the surface of a Kirschner (K)-wire was established. In the present study, two models of mature biofilm using clinical Staphylococcus aureus strains were assessed: one related to contaminated K-wires (in vitro biofilm maturation) and the second to hematogenous infections (in vivo biofilm maturation). Rifampicin was used as a standard drug for antibiofilm treatment.

Method

In the first model, biofilms were formed following an incubation period (up to 7 days) in the CDC Biofilm Reactor (CBR, BioSurface Technologies). Then, after implantation of the pre-incubated K-wire in the larvae, rifampicin (80 mg/kg) was injected and the survival of the larvae was monitored. In the second model, biofilm formation was achieved after an incubation period (up to 7 days) inside the larvae and then, after removing the K-wires from the host, in vitro rifampicin susceptibility assays were performed (according to EUCAST).


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 76 - 76
22 Nov 2024
Gardete-Hartmann S Sebastian S Berdalli S Simon S Hofstaetter J
Full Access

Aim

Unexpected negative-cultures (UNC) are a common diagnostic problem in periprosthetic joint infection (PJI) of the hip and knee when using culture-based methods. A novel molecular approach (MC)1 based on the identification of the vast majority of bacterial species in a single assay using species-specific bacterial interspacing region length polymorphisms and phylum-specific 16S rDNA sequence polymorphisms has demonstrated clinical utility in PJI diagnostics (1). In addition, MC provides an estimate of the leukocyte concentration in the specimen analysed. The aim of this retrospective, blinded study was to evaluate the performance of MC in identifying the microbiological content and determining the leukocyte count in synovial fluid (SF) collected from hip and knee revision arthroplasty cases with UNC. It was also assessed whether antibiotic treatment would have been changed if the result from MC had been known.

Method

A total of 89 SF samples from 70 patients (43 female; 27 male) who underwent revision arthroplasty (14 hip; 75 knee) were included. Using European and Bone Joint Infection Society (EBJIS) criteria, 82 cases were classified as infected (77 UNC and 5 septic culture-positive controls), five as non-infected (aseptic culture-negative controls), and two as likely infected, but infected by clinical observation. MC was performed and evaluated together with SF parameters. Antibiotic treatment, clinical outcome, patient demographics and surgical details were analysed.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 37 - 37
22 Nov 2024
Vitiello R Smimmo A Taccari F Matteini E Micheli G Fantoni M Maccauro G
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Aim

Periprosthetic joint infection (PJI) is a devastating complication that develops after total joint arthroplasty (TJA) whose incidence is expected to increase over the years. Traditionally, surgical treatment of PJI has been based on algorithms, where early infections are preferably treated with debridement, antibiotics, and implant retention (DAIR), while late infections with two-stage revision surgery. Two-stage revision is considered the “gold standard” for treatment of chronic PJI. In this observational retrospective study, we investigated the potential role of inflammatory blood markers (neutrophil-to- lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic inflammatory index (SII)], systemic inflammatory response index (SIRI), and aggregate index of systemic inflammation (AISI)) as prognostic factors in two-stage exchange arthroplasty for PJI.

Method

A single-center retrospective analysis was conducted, collecting clinical data and laboratory parameters from patients submitted to prosthetic explantation for chronic PJI. Laboratory parameters (PCR, NLR, MLR, PLR, SIRI, SII and AISI) were evaluated at the explantation time, at 4, 6, 8 weeks after surgery and at reimplantation time. Correlation between laboratory parameters and surgery success was evaluated, defined as infection absence/resolution at the last follow up


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 22 - 22
22 Nov 2024
Söderquist B Möller M Salihovic S
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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.