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Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 41 - 41
24 Nov 2023
Lilleøre JG Jørgensen A Knudsen M Hanberg P Öbrink-Hansen K Tøstesen S Søballe K Stilling M Bue M
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Background and aim

Implant-associated osteomyelitis is one of the most feared complications following orthopedic surgery. Although the risk is low it is crucial to achieve adequate antibiotic concentrations proximate to the implant for a sufficient amount of time to protect the implant surface and ensure tissue integration. The aim of this study was to assess steady-state piperacillin concentrations in the proximity of an orthopedic implant inserted in cancellous bone.

Method

Six female pigs received an intravenous bolus infusion of 4 g/0.5 g piperacillin/tazobactam over 30 min every 6 h. Steady state was assumed achieved in the third dosing interval (12–18 h). Microdialysis catheters were placed in a cannulated screw in the proximal tibial cancellous bone, in cancellous bone next to the screw, and in cancellous bone on the contralateral tibia. Dialysates were collected from time 12 to 18 h and plasma samples were collected as reference.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 69 - 69
1 Dec 2018
Bue M Hanberg P Tøttrup M Thomassen M Sorensen HB Thillemann TM Andersson TL Søballe K
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Aims

Vancomycin may be an important drug for intravenous perioperative antimicrobial prophylaxis in spine surgery. We assessed single-dose vancomycin intervertebral disc, vertebral cancellous bone, and subcutaneous adipose tissue concentrations using microdialysis in a pig model.

Methods

8 female pigs received 1,000 mg of vancomycin intravenously as a single dose over 100 minutes. Microdialysis probes were placed in the C3-C4 intervertebral disc, C3 vertebral cancellous bone, and subcutaneous adipose tissue, and vancomycin concentrations were obtained over 8 hours. Venous blood samples were obtained as reference.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 45 - 45
1 Dec 2018
Bue M Hanberg P Koch J Jensen LK Lundorff M Aalbæk B Jensen HE Søballe K Tøttrup M
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Aim

The increasing incidence of orthopaedic methicillin-resistant Staphylococcus aureus (MRSA) infections represents a significant therapeutic challenge. Being effective against MRSA, the role of vancomycin may become more important in the orthopaedic setting in the years to come. Nonetheless, vancomycin bone and soft tissue penetration during infection remains unclear. We assessed the effect of a traumatically induced, implant-associated acute osteomyelitis on vancomycin bone penetration in a porcine model.

Method

In eight pigs, implant-associated osteomyelitis was induced on day 0, using a Staphylococcus aureus strain. Following administration of 1,000 mg of vancomycin on day 5, vancomycin concentrations were obtained with microdialysis for eight hours in the implant bone cavity, in cancellous bone adjacent to the implant cavity, in subcutaneous adipose tissue (SCT) adjacent to the implant cavity, and in healthy cancellous bone and healthy SCT in the contralateral leg. Venous blood samples were also obtained. The extent of infection and inflammation was evaluated by post-mortem computed tomography scans, C-reactive protein serum levels and cultures of blood and swabs.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_22 | Pages 62 - 62
1 Dec 2017
Hanberg PE Bue M Sørensen HB Søballe K Tøttrup M
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Aim

Pyogenic spondylodiscitis is associated with prolonged antimicrobial therapy and high relapse rates. Nevertheless, tissue pharmacokinetic studies of relevant antimicrobials in both prophylactic and therapeutic situations are still sparse. Previous approaches based on bone biopsy and discectomy exhibit important methodological limitations. The objective of this study was therefore to assess the concentration of cefuroxime in intervertebral disc (IVD), vertebral body cancellous bone, subcutaneous adipose tissue (SCT) and plasma pharmacokinetics after single dose administration by use of microdialysis (MD) in a large animal model.

Method

Ten female pigs were assigned to receive 1,500 mg of cefuroxime intravenously over 15 min. Measurements of cefuroxime were obtained from plasma, SCT, the vertebral cancellous bone and the IVD for 8 hours thereafter. MD was applied for sampling in solid tissues. The cefuroxime concentration in both the MD and plasma samples was determined using ultra-high performance liquid chromatography.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_22 | Pages 74 - 74
1 Dec 2017
Bue M Tøttrup M Hanberg P Langhoff O Sorensen HB Thillemann TM Andersson TL Søballe K
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Aim

The incidence of orthopaedic methicillin-resistant staphylococcus aureus infections is increasing. Vancomycin may therefore play an increasingly important role in orthopaedic perioperative antimicrobial prophylaxis. Adequate antimicrobial concentrations at target site is essential for prevention of orthopaedic infections. Current studies investigating perioperative bone and soft tissue concentrations of vancomycin are sparse and challenged by a lack of appropriate methods. The aim of this study was therefore to assess the concentration of vancomycin in plasma, subcutaneous tissue and bone after single dose administration using microdialysis (MD) in patients undergoing total knee replacement.

Method

1,000 mg of vancomycin was postoperatively administered intravenously over 100 minutes to 10 male patients undergoing primary total knee replacement. Vancomycin concentrations in plasma, subcutaneous tissue (SCT), cancellous and cortical bone were measured the following 8 hours. MD was applied for sampling in solid tissues. The vancomycin concentration in MD-samples was determined using ultra-high performance liquid chromatography, whilst the free plasma concentration was determined using a chemistry analyzer*.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_22 | Pages 89 - 89
1 Dec 2017
Lange J Troelsen A Solgaard S Ørsnes T Otte K Nielsen PT Lamm M Krarup N Mikkelsen S Zawadski A Søballe K
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Aim

Our aim was to evaluate cementless one-stage revision in chronic periprosthetic hip joint infection.

Method and patients

The study was performed as a multicentre, proof-of-concept, observational study with prospective data collection. Inclusion of patients with a chronic periprosthetic hip joint infection (PJI) were followed by protocolled surgical treatment (cementless one-stage revision - the CORIHA protocol) at one of 8 participating departments of orthopaedic surgery between 2009 – 2014, and the patients enrolled in a 2-year follow-up program. A PJI were diagnosed based on adopted criteria from McPherson and Zimmerli. At the time of initiation of the study in 2009, the collaborating departments performed approximately one-fourth of all nationwide primary HJR and more than one-third of all revisions.

In total 56 PJI patients with a median age of 72 years and a median pre-operative ASA score of 2 met the established eligibility criteria and accepted to participate; 31 (55%) were males.

The cohort had a mean follow-up time of 4.0 years, with all patients followed for minimum 2 years.

The primary outcome were relapse described as re-revision due to infection (regardless of considered as a relapse or new infection). This was evaluated by competing risk analysis (competing risks: aseptic revisions and death).

Secondary, all-cause mortality was evaluated by survival analysis.

The study was approved by the local Committees on Biomedical Research Ethics.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_22 | Pages 95 - 95
1 Dec 2017
Falstie-Jensen T Daugaard H Lange J Ovesen J Søballe K
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Background

Periprostetic joint infections (PJI) are often difficult to diagnose, to treat and often leave the patient with severe impaired function. The presence of low virulent bacteria is frequently discovered in apparent aseptic revisions of shoulder arthroplasties and pose a challenge to diagnose preoperatively.

Dual Isotope In111 Leucocyte/ Tc99 Bone Marrow SPECT CT scan (L/BMS) is considered the radionuclide gold standard in preoperative diagnosing PJI with reported high specificity and sensitivity in hip and knee arthroplasties.

Unfortunately, it is labour-intensive and expensive to perform and documentation using L/BMS on shoulder arthroplasties lack.

Aim

To investigate if L/BMS succeeds in detecting shoulder PJI compared to tissue cultures obtained perioperatively.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_23 | Pages 77 - 77
1 Dec 2016
Tøttrup M Bue M Koch J Jensen LK Hanberg P Aalbæk B Fuursted K Jensen HE Søballe K
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Aim

A reason for treatment failure, in cases of periprosthetic bone infections and osteomyelitis, may be incomplete or heterogeneous tissue distribution of antimicrobials to the affected bone. Decreased bioavailability has been demonstrated in healthy bones but never in pathological bone tissue. Therefore, the aim was to obtain pharmacokinetic parameters of cefuroxime in infected bone tissue by means of microdialysis in a porcine model of implant associated osteomyelitis

Method

An implant cavity of 4 mm in diameter was drilled 25 mm into the right tibial bone of ten pigs (30 kg/BW). Subsequently, a small steel implant (K-wire 2 × 2 mm) and 104 CFU of Staphylococcus aureus was inserted and injected into the implant cavity. Five days after inoculation, two additional drill holes of 2 × 25 mm were drilled into the trabecular bone tissue adjacent to the implant cavity and into the left uninfected tibia. After intravenous administration of 1500 mg of cefuroxime, the concentration was measured in plasma and in the three tibial drill holes for 8 hours. All measurements were performed with microdialysis. Post mortem, the presence of bone infection was assessed by computed tomography (CT) scans and cultures of swabs.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_15 | Pages 7 - 7
1 Dec 2015
Lange J Pedersen A Troelsen A Søballe K
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There is an apparent need for easily accessible research data on Periprosthetic hip joint infections (PJI)(1). Administrative discharge registers could be a valuable single-sources for this purpose, and studies originating from such registers have been published(2–4). However, the quality of routinely collected data for administrative purposes may be questionable for use in epidemiological research. The aim of this study was to estimate the positive predictive value of the International Classification of Disease 10th revision (ICD-10) periprosthetic hip joint infection diagnose code T84.5.

The study was performed as a cross-sectional study on data extracted from the Danish National Patient Register. Patients with a registration of performed surgical treatment for hip PJI were identified via the ICD-10 code T84.5 (Infection and inflammatory reaction due to internal joint prosthesis) in association with hip-joint associated surgical procedure codes. Medical records of the identified patients (n=283) were verified for the existence of a periprosthetic hip joint infection. Positive predictive values with 95% confidence intervals (95% CI) were calculated.

A T84.5 diagnosis code irrespective of the associated surgical procedure code had a positive predictive value of 85 % (95% CI: 80–89). Stratified to T84.5 in combination with an infection-specific surgical procedure code the positive predictive value increased to 86% (95% CI: 80–91), and in combination with a noninfection-specific surgical procedure code decreased to 82% (95% CI: 72–89).

This study is the first to evaluate the only discharge diagnose code of prosthesis-related infection in an administrative discharge register. It is apparent, that codes in administrative discharge registers are prone to misclassification on an administrative level, either by wrongful coding by the physician or administrative personal in the registration process. Misclassification must be expected and taken into consideration when using single-source administrative discharge registers for epidemiological research on periprosthetic hip joint infection. We believe that the periprosthetic hip joint infection diagnose code can be of use in single-source register based studies, but preferably should be used in combination with alternate data sources to ensure higher validity(5)

This study is funded in part by the Lundbeck foundation Centre for Fast-track Hip and Knee Surgery, Denmark.