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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 47 - 47
22 Nov 2024
Mitterer JA Hartmann SG Simon S Sebastian S Chlud L Hofstaetter JG
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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.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 80 - 80
22 Nov 2024
Simon S Wouthuyzen-Bakker M Mitterer JA Gardete-Hartmann S Frank BJ Hofstaetter J
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Aim

It still remains unclear whether postoperative antibiotic treatment is advantageous in presumed aseptic revision-arthroplasties of the hip (rTHA) and knee (rTKA) with unexpected-positive-intraoperative-cultures (UPIC). The aim of this study was to evaluate if there is a difference in the septic and/or aseptic re-revision rate in patients with or without postoperative antibiotics.

Method

In this retrospective propensity-score (PS) matched cohort-study we compared the re-revision rate and the microbiological spectrum in rTHA and rTKA treated with (AB-Group; n=70) and without (non-AB-Group; n=70) antibiotic treatment in patients with UPIC. Baseline covariates for PS-matching were type of revision, sex, Body-Mass-Index, age, Surgical-Site-Infection-Score, American-Society-of-Anesthesiologists-Classification, serum C-reactive-protein.

All patients received routine antibiotic prophylaxis, but empiric AB treatment was started only in patients in the AB-Group. Post-operative treatment was decided on an individual basis according to the preference of the surgeon and the infectious disease specialist for a minimum duration of two weeks. In total, 90 rTHA (45 AB-Group, 45 in non-AB-Group) patients with UPICs and 50 rTKA (25 AB-Group, 25 in non-AB-Group) were included in the study. There was no significant variation in patient demographics.


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
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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. 105-B, Issue SUPP_17 | Pages 21 - 21
24 Nov 2023
Hartmann KT Nielsen RL Mikkelsen F Ingmer H Kvich LA Aalbaek B Odgaard A Jensen HE Lichtenberg M Bjarnsholt T Jensen LK
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Aim

To make an inoculum for induction of Implant-Associated Osteomyelitis (IAO) in pigs based on bacterial aggregates resembling those found on the human skin, i.e. aggregates of 5–15 µm with low metabolic activity. The aggregates were evaluated and compared to a standard planktonic bacterial inoculum.

Method

The porcine Staphylococcus aureus strain S54F9 was cultured in Tryptone Soya Broth for seven days. Subsequently, the culture was filtered through cell strainers with pore sizes of 15 µm and 5 µm, respectively. The fraction of 5–15 µm aggregates in the top of the 5 µm filter was collected as the aggregate-inoculum. The separation of aggregates into different size fractions was evaluated by light microscopy. The metabolism of the aggregate-inoculum and a standard overnight planktonic inoculum was evaluated with isothermal microcalorimetry. In total, six female minipigs were allocated into three groups (n=2), receiving different inoculums. Group A: overnight planktonic inoculum; 104 CFU S. aureus (S54F9), Group B: seven days old 5–15 µm aggregate-inoculum; 104 CFU S. aureus (S54F9), Group C: saline. All inoculums were placed in a pre-drilled implant cavity in the right tibia of the pig and a sterile stainless-steel implant was inserted. The pigs were euthanized seven days after surgery. Postmortem macroscopic pathology, microbiology, computed tomography and histopathology were performed.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 60 - 60
24 Nov 2023
Simon S Frank BJ Hartmann SG Mitterer JA Sujeesh S Huber S Hofstaetter JG
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Aims

The aim of this study was to assess the incidence the microbiological spectrum and clinical outcome of hip and knee revision arthroplasties with unexpected-positive-intraoperative-cultures (UPIC) at a single center with minimum follow up of 2 years.

Methods

We retrospectively analyzed our prospectively maintained institutional arthroplasty registry. Between 2011 and 2020 we performed presumably aseptic rTHA (n=939) and rTKA (n= 1,058). Clinical outcome, re-revision rates and causes as well as the microbiological spectrum were evaluated.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 67 - 67
24 Nov 2023
Gardete-Hartmann S Simon S Frank BJ Sebastian S Loew M Sommer I Hofstaetter J
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Aim

Synovial calprotectin point-of-care test (POC) has shown promising clinical value in diagnosing periprosthetic joint infections (PJIs). However, limited data are available in unclear cases. Moreover, cut-off values for calprotectin lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) need to be adapted. The aim of this study was to evaluate the performance of an upgraded and more sensitive version of a synovial calprotectin LFA along with ELISA immunoassay in patients with septic, aseptic, and unclear cases.

Methods

Overall, 206 prospectively collected periprosthetic synovial fluid samples from 169 patients (106f/63m; 38 hip/131 knee) who underwent revision surgeries were retrospectively evaluated for calprotectin concentration. The following groups were analyzed: unexpected negative cultures (UNC; 32/206), unexpected positive cultures (UPC; 28/206), and unclear cases (65/206) with conflicting clinical results. In addition, we added a true aseptic (40/206), and true septic (41/206) control groups according to the international consensus meeting (ICM) 2018 PJI classification. Calprotectin concentration was determined by a rapid quantitative LFA (n=206) (Lyfstone®, Norway), and compared to calprotectin ELISA immunoassay (171/206). For the determination of a new calprotectin cut-off value, analysis of the area under the curve (AUC) followed by Youden's J statistic were performed using the calproctectin values from clear septic and aseptic cases. Sensitivity and specificity for calprotectin were calculated. All statistical analyses were performed using IBM-SPSS® version 25 (Armonk, NY, USA).


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 61 - 61
1 Oct 2022
Fuglsang-Madsen A Henriksen NL Kvich LA Birch JKM Hartmann KT Bjarnsholt T Andresen TL Jensen LK Henriksen JR Hansen AE
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Aim

Several local antibiotic-eluting drug delivery systems have been developed to treat bacterial bone infections. However, available systems have significant shortcomings, including suboptimal drug-release profiles with a burst followed by subtherapeutic release, which may lead to treatment failure and selection for drug resistance.

Here, we present a novel injectable, biocompatible, in situ-forming depot, termed CarboCells, which can be fine-tuned for the desired antibiotic-release profile. The CarboCell technology has flexible injection properties that allow surgeons to accurately place antibiotic-eluting depots within and surrounding infectious sites in soft tissue and bones. The CarboCell technology is furthermore compatible with clinical image-guided injection technologies.

These studies aimed to determine the therapeutic potential of CarboCell formulations for treatment of implant-associated osteomyelitis by mono- and dual antimicrobial therapy.

Methods

The solubility and stability of several antibiotics were determined in various CarboCell formulations, and in vitro drug release was characterized. Lead candidates for antimicrobial therapy were selected using a modified semi-solid biofilm model with 4-day-matured Staphylococcus aureus biofilm (osteomyelitis-isolate, strain S54F9). Efficacy was investigated in a rat implant-associated osteomyelitis model established in the femoral bone by intraosseous implantation of a stainless-steel pin with 4-day-old in vitro-matured S. aureus biofilm. CarboCells were injected subcutaneously at the femur, and antimicrobial efficacy was evaluated 7 days post-implantation. Lead formulations were subsequently tested in a well-established translational implant-associated tibial S. aureus osteomyelitis pig model. Infection was established for 7 days before revision surgery consisting of debridement, washing, implantation of a new stainless-steel pin, and injection of antibiotic-releasing CarboCells into the debrided cavity and in the surrounding bone- and soft-tissue. Seven days post-revision, pigs were euthanized, and samples were collected for microbial and histopathological evaluation.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 5 - 5
1 Oct 2022
Hartmann S Mitterer JA Frank BJH Simon S Prinz M Dominkus M Hofstätter J
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Aim

Culture-based conventional methods are still the gold standard to identify microorganisms in hip and knee PJIs diagnosis. However, such approach presents some limitations due to prior antimicrobial treatment or the presence of unusual and fastidious organisms. Molecular techniques, in particular specific real-time and broad-range polymerase chain reaction (PCR), are available for diagnostic use in a suspected PJI. However, limited data is available on their sensitivity and specificity.

This study aimed to evaluate the performance of a rapid and simple Investigational Use Only (IUO) version of the BioFire® JI multiplex PCR panel when compared to traditional microbiological procedures.

Method

Fifty-eight native synovial fluid samples were recovered from 49 patients (female n=26; male =23) who underwent one or multiple septic or aseptic revision arthroplasties of the hip (n=12) and knee (n=46). The JI panel methodology was used either on specimens freshly collected (n=6) or stored at −80°C in our Musculoskeletal Biobank (n=52). The JI panel performance was evaluated by comparison with culture reference methods. Patient's medical records were retrieved from our institutional arthroplasty registry as well as our prospectively maintained PJI infection database.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 22 - 22
1 Oct 2022
Frank BJ Aichmair A Hartmann S Simon S Dominkus M Hofstätter J
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Aim

Analysis of microbiological spectrum and resistance patterns as well as the clinical outcome of patients who underwent a Debridement, antibiotics and implant retention (DAIR) procedure in the early phase following failed two-stage exchange arthroplasty of the knee and hip.

Method

Of 312 patients treated with two-stage exchange arthroplasty between January 2011 and December 2019, 16 (5.1%) patients (9 knee, 7 hip) underwent a DAIR procedure within 6 months following second stage. We retrospectively analyzed the microbiological results as well as changes in the microbiological spectrum and antibiotic resistance patterns between stages of two-stage exchange arthroplasties and DAIR procedures. Patient's re-revision rates after a minimum follow-up of 12 months following DAIR procedure were evaluated. Moreover, differences between knee and hip and between infected primary total joint replacement (TJRs) and infected revision TJRs as well as patient's host factors and microbiological results regarding the outcome of DAIR were analyzed.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 1 - 1
1 Oct 2022
Simon S Frank BJH Aichmair A Dominkus M Mitterer JA Hartmann S Kasparek M Hofstätter J
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Purpose

Unexpected-positive-intraoperative-cultures (UPIC) in presumed aseptic revision-total-knee-arthroplasties (rTKA) are common, and the clinical significance is not entirely clear. In contrast, in some presumably septic rTKA, an identification of an underlying pathogen was not possible, so called unexpected-negative-intraoperative-cultures (UNIC). The purpose of this study was to evaluate alpha defensin (AD) levels in these patient populations.

Methods

In this retrospective analysis of our prospectively maintained biobank, we evaluated synovial AD levels from 143 rTKAs. The 2018-Musculoskeletal Infection Society score (MSIS) was used to define our study groups. Overall, 20 rTKA with UPIC with a minimum of one positive intraoperative culture with MSIS 2-≥6 and 14 UNIC samples with MSIS≥6 were compared to 34 septic culture-positive samples (MSIS ≥6) and 75 aseptic culture-negative (MSIS 0–1) rTKAs. Moreover, we compared the performance of both AD-lateral-flow-assay (ADLF) and an enzyme-linked-immunosorbent-assay (ELISA) to test the presence of AD in native and centrifuged synovial fluid. Concentration of AD determined by ELISA and ADLF methods, as well as microbiological, and histopathological results, serum and synovial parameters along with demographic factors were considered.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 54 - 54
1 Oct 2022
Mitterer JA Frank BJ Gardete-Hartmann S Panzenboek LF Simon S Krepler P Hofstaetter JG
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Aim

In severe cases of postoperative spinal implant infections (PSII) multiple revision surgeries may be needed. Little is known if changes of the microbiological spectrum and antibiotic resistance pattern occur between revision surgeries. Therefore, the aim of this study was to analyze the microbiological spectrum and antibiotic resistance pattern in patients with multiple revision surgeries for the treatment of PSII. Furthermore, changes of the microbiological spectrum, distribution of mono vs. polymicrobial infections, and changes of the antimicrobial resistance profile in persistent microorganisms were evaluated.

Method

A retrospective analysis of a prospectively maintained single center spine infection database was performed with a minimum follow-up of 3 years. Between 01/2011 and 12/2018, 103 patients underwent 248 revision surgeries for the treatment of PSII. Overall, 20 patients (6 male/14 female) underwent 82 revisions for PSII (median 3; range 2–12). There were 55/82 (67.1%) procedures with a positive microbiological result. Microbiological analysis was performed on tissue and implant sonication fluid. Changes in microbial spectrum and antibiotic resistance pattern between surgeries were evaluated using Chi-Square and Fisher's exact test.