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Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 27 - 27
24 Nov 2023
Chen B Chittò M Benavente LP Post V Moreno MG Zeiter S Trampuz A Wagemans J Lavigne R Onsea J Metsemakers W Moriarty F
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Aim

Bacteriophages are remerging as alternative and adjunctive therapy for fracture-related infection (FRI). However, current administration protocols involve prolonged retention of a percutaneous draining tube with potential risk of developing superinfection. In this study, we applied a cocktail of in vitro evolved biofilm-targeting phages for Methicillin-resistant Staphylococcus aureus (MRSA) in a hydrogel platform co-delivering vancomycin. In vitro synergy and antibiofilm activity was assessed and a subsequent in vivo study was performed in a mouse FRI model with MRSA.

Method

Two evolved bacteriophages (MRSA-R14 and COL-R23) with improved antibiofilm activity against a clinical isolate (MRSA3) were tested in combination with vancomycin and a carboxymethylcellulose (CMC) hydrogel in vitro and in vivo. MRSA3 bacterial biofilms were formed on sterile 4 mm sintered porous glass beads at 37 °C for 24 h. Biofilms were exposed to i-phage cocktail (107 PFU/ml), ii-vancomycin at concentrations of 0.5, 1, 10 and 100 times the MIC, or iii-combination of phage cocktail and vancomycin. Recovered biofilm cells, were quantified by colony counting. The stability and release profiles of phage cocktail and vancomycin in co-delivery hydrogel were assessed in vitro for 8 days and 72 hrs, respectively, and subsequently tested in the treatment of 5-day-old MRSA3 infection of a femoral plate osteotomy in mice.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 11 - 11
24 Nov 2023
Sliepen J Buijs M Wouthuyzen-Bakker M Depypere M Rentenaar R De Vries J Onsea J Metsemakers W Govaert G IJpma F
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Aims

Fracture-Related Infection (FRI) is a severe complication caused by microbial infection of bone. It is imperative to gain more insight into the potentials and limitations of Debridement, Antibiotics and Implant Retention (DAIR) to improve future FRI treatment. The aims of this study were to: 1) determine how time to surgery affects the success rate of DAIR procedures of the lower leg performed within 12 weeks after the initial fracture fixation operation and 2) evaluate whether appropriate systemic antimicrobial therapy affects the success rate of a DAIR procedure.

Methods

This multinational retrospective cohort study included patients of at least 18-years of age who developed an FRI of the lower leg within 12 weeks after the initial fracture fixation operation, between January 1st 2015 to July 1st 2020. DAIR success was defined by the absence of recurrence of infection, preservation of the affected limb and retention of implants during the initial treatment. The antimicrobial regimen was considered appropriate if the pathogen(s) was susceptible to the given treatment at the correct dose as per guideline. Logistic regression modelling was used to assess factors that could contribute to the DAIR success rate.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 19 - 19
24 Nov 2023
McNally M Alt V Wouthuyzen M Marais L Metsemakers W Zalavras C Morgenstern M
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Aim

To classify Fracture-related Infection (FRI) allowing comparison of clinical studies and to guide decision-making around the main surgical treatment concepts.

Method

An international group of FRI experts met in Lisbon, June 2022 and proposed a new FRI classification. A core group met during the EBJIS Meeting in Graz, 2022 and on-line, to determine the preconditions, purpose, primary factors for inclusion, format and the detailed description of the elements of an FRI Classification.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 13 - 13
24 Nov 2023
Sliepen J Hoekstra H Onsea J Bessems L Depypere M Herteleer M Sermon A Nijs S Vranckx J Metsemakers W
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Aim

The number of operatively treated clavicle fractures has increased over the past decades. Consequently, this has led to an increase in secondary procedures required to treat complications such as fracture-related infection (FRI). The primary objective of this study was to assess the clinical and functional outcome of patients treated for FRI of the clavicle. The secondary objectives were to evaluate the healthcare costs and propose a standardized protocol for the surgical management of this complication.

Method

All patients with a clavicle fracture who underwent open reduction and internal fixation (ORIF) between 1 January 2015 and 1 March 2022 were retrospectively evaluated.

This study included patients with an FRI who were diagnosed and treated according to the recommendations of a multidisciplinary team at the University Hospitals Leuven, Belgium.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 10 - 10
1 Oct 2022
Sweere V Sliepen J Haidari S Depypere M Mertens M IJpma F Metsemakers W Govaert G
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Aim

Fracture-related infection (FRI) is one of the most serious complications in orthopedic trauma surgery [1]. The role of Negative Pressure Wound Therapy (NPWT) remains controversial in the management pathway of FRI [2]. Currently, as scientific evidence is lacking, most recommendations for NPWT with respect to the treatment of FRI are based on expert opinion [3]. The aim of this study was to assess the influence of NPWT and its duration on recurrence of infection in operatively treated FRI patients.

Methods

This is a retrospective cohort study based on the FRI database of three Level 1 Trauma Centres. To be included, patients had to be at least 16 years of age and needed to be surgically treated for FRI between January 1st 2015 and September 1st 2020. Included patients were subdivided in either the NPWT group, or in the control group, when no NPWT had been applied. To avoid confounding, patients were excluded if they (also) underwent NPWT prior to the FRI diagnosis. The relation between the duration of NPWT during FRI treatment and the recurrence rate of infection was analyzed using a multivariable logistic regression model.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 14 - 14
1 Oct 2022
Sliepen J Depypere M Onsea J Debaveye Y Govaert G Ijpma F Zimmerli W Metsemakers W
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Purpose

Fracture-related infection (FRI) is an important complication related to orthopaedic trauma. Although the scientific interest with respect to the diagnosis and treatment of FRI is increasing, data on the microbiological epidemiology remains limited. Therefore, the primary aim of this study was to evaluate the microbiological epidemiology related to FRI, including the association with clinical symptoms and antimicrobial susceptibility data. The secondary aim was to analyze whether there was a relationship between the time to onset of infection and the microbiological etiology of FRI.

Methods

Over a five-year period, FRI patients treated at the University Hospitals of Leuven, Belgium, were retrospectively included. The microbiological etiology and antimicrobial susceptibility data were analyzed. Patients were classified as having an early (<2 weeks after implantation), delayed (2–10 weeks) or late-onset (> 10 weeks) FRI.


Bone & Joint Research
Vol. 10, Issue 6 | Pages 351 - 353
1 Jun 2021
Baertl S Metsemakers W Morgenstern M Alt V Richards RG Moriarty TF Young K


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_5 | Pages 3 - 3
1 Mar 2021
Wittauer M Burch M Vandendriessche T Metsemakers W Morgenstern M
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Aim

Although non-unions being one of the most common complication after long-bone fracture fixation, the definition of this entity remains controversial and varies widely among authors. A clear definition is crucial, not only for the evaluation of published research data but also for the establishment of uniform treatment concepts. The aim of this systematic review was to identify the definitions and different criteria used in the scientific literature to describe non-unions after long bone fractures.

Method

A comprehensive literature search was performed in PubMed, Cochrane Library, Web of Science, and Embase. according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Prospective therapeutic and diagnostic clinical studies in which adult long-bone fracture non-unions were investigated as main subject were included in this analysis.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_14 | Pages 57 - 57
1 Dec 2019
Bezstarosti H van Lieshout E Voskamp L Croughs P Kortram K McNally M Metsemakers W Verhofstad M
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Aim

The aim of this systematic review was to determine all cultured bacteria, antibiotic strategies, and their outcome from literature describing treatment of FRI patients between 1990 and 2018.

Methods

A systematic literature search was performed on treatment and outcome of FRI. All studies in English that described surgical patient series for treatment of FRI were included, using Medline, Embase, Web of Science, Cochrane, and Google Scholar. Publications before 1990 and studies that did not describe FRI patient treatment or did not report original data (e.g., reviews or meta-analyses) were excluded. Study selection and data collection were done by two authors independently. Main collected parameters were preoperative cultures, use of local antibiotics, postoperative antibiotic protocol, cultured microorganisms, and overall outcome of treatment, i.e., eradication of infection and bony union, recurrence, amputations, revisional surgery, and number of complications. Dichotomous data were pooled using Medcalc, and weighted means were calculated for continuous data using Excel.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_14 | Pages 36 - 36
1 Dec 2019
Depypere M Moonen C Alaerts R Hoekstra H Sermon A Nijs S Metsemakers W
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Aim

Negative-pressure wound therapy (NPWT) is often propagated as treatment option for fracture-related infection (FRI). After surgical debridement and repeated NPWT dressing changes, the wounds are often closed by free flaps. Sometimes even healing by secondary intention seems an alternative. Recently, concerns have been raised on the long-term use of NPWT as it could be related to bacterial overgrowth and possible re-infection. The purpose of this study was to conduct a retrospective evaluation of the influence of long-term NPWT on tissue culture results and outcome in FRI patients

Method

Between January 1st, 2015 and December 31st, 2018, a total of 852 patients were treated with NPWT for different indications on the Department of Trauma Surgery. Inclusion criteria for this study were patients with a closed fracture, stabilized with osteosynthetic fixation and complicated with a confirmed FRI according to the FRI consensus definition. Patients were included when they received at least three NPWT dressing changes in the operating room. Exclusion criteria were patients younger than 18 years, or the absence of cultures results from dressing changes.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 25 - 25
1 Dec 2018
Bezstarosti H Metsemakers W van Lieshout E Kortram K Voskamp L McNally M Verhofstad MHJ
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Aim

The aim of this systematic review was to determine the reported treatment strategies, their individual success rates, and other outcome parameters in the management of critical-sized bone defects in Fracture-Related Infection (FRI) patients between 1990 and 2018.

Method

We performed a systematic literature search on treatment and outcome of critical-sized bone defects in FRI. Treatment strategies identified were, autologous cancellous grafts, autologous cancellous grafts combined with local antibiotics, the induced membrane technique, vascularized grafts, bone transport, and bone transport combined with local antibiotics. Studies describing bone defects of 1 cm or greater were included. Outcomes were bone healing and infection eradication after primary surgical protocol and recurrence of FRI and amputations at the end of study period.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 89 - 89
1 Dec 2018
Morgenstern M Vallejo A McNally M Moriarty F Ferguson J Nijs S Metsemakers W
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Aim

Alongside debridement and irrigation, soft tissue coverage and osseous stabilization, systemic antibiotic prophylaxis is considered the gold standard in the management of open fractures and considerably reduces the risk of subsequent fracture-related Infections (FRI). The direct application of antibiotics into the surgical field (local antibiotics) has been used for decades as additional prophylaxis in open fractures, although definitive evidence confirming a beneficial effect is scarce. The purpose of the present study was to review the clinical evidence regarding the effect of prophylactic application of local antibiotics in open limb fractures.

Method

A comprehensive literature search was performed in PubMed, Web-of- Science and Embase. Cohort studies investigating the effect of additional local antibiotic prophylaxis compared to systemic prophylaxis alone in the management of open fractures were included and the data were pooled in a meta-analysis.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 75 - 75
1 Dec 2018
van den Kieboom J Bosch P Plate J IJpma F Leenen L Kühl R McNally M Metsemakers W Govaert G
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Aim

Fracture related infection (FRI) remains a challenging diagnosis in orthopedic and trauma surgery. In addition to clinical signs and imaging, serum inflammatory markers are often used to estimate the probability of FRI. To what extent serum inflammatory markers can be used to rule out and diagnose FRI remains unclear. The aim of this systematic review was to assess the diagnostic value of the serum inflammatory markers C-reactive protein (CRP), leukocyte count (LC) and erythrocyte sedimentation rate (ESR) in suspected fracture related infection.

Method

PubMed, Embase and Cochrane databases were searched for all articles focusing on the diagnostic value of CRP, LC and ESR in FRI. Studies on other inflammatory markers or other types of orthopedic infection, such as periprosthetic and diabetic foot infections, were excluded. For each serum inflammatory marker, all reported sensitivity and specificity combinations were extracted and graphically visualized. Average estimates were obtained using bivariate mixed effects models. This study utilized the QUADAS-2 criteria and was reported following the PRISMA statement.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 24 - 24
1 Dec 2018
Pützler J Zalavras C Moriarty F Verhofstad MHJ Stephen K Raschke M Rosslenbroich S Metsemakers W
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Aim

Infection rates after management of open fractures are still high. Existing guidelines regarding prevention of this complication are inhomogeneous. A survey directed to orthopaedic trauma surgeons worldwide aims to give an overview of current practices in the management of open fractures.

Method

An international group of trauma surgeons and infection specialists with experience in the field of musculoskeletal infections developed a questionnaire that was distributed via email to all AOTrauma members worldwide. Descriptive statistical analysis was performed.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 16 - 16
1 Dec 2018
Declercq P Nijssen A Quintens J De Ridder T Merten B Mesure J Nijs S Zalavras C Spriet I Metsemakers W
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Aim

Duration of perioperative antimicrobial prophylaxis (PAP) remains controversial in prevention of fracture-related infection (FRI) – with rates up to 30% - in open fracture (OF) management. Objectives were to investigate the impact of the PAP duration exclusively in or related to long bone OF trauma patients and the influence of augmented renal clearance (ARC), a known phenomenon in trauma patients, as PAP consists of predominantly renally eliminated antibiotics.

Method

Trauma patients with operatively treated OF, admitted between January 2003 and January 2017 at the University Hospitals Leuven, were retrospectively evaluated. FRI was defined following the criteria of the consensus definition of FRI. A logistic regression model was conducted with FRI as outcome. Results were considered statistically significant when p< 0.05.


The Bone & Joint Journal
Vol. 100-B, Issue 12 | Pages 1542 - 1550
1 Dec 2018
van den Kieboom J Bosch P J. Plate JD A. IJpma FF Kuehl R McNally MA Metsemakers W M. Govaert GA

Aims

To assess the diagnostic value of C-reactive protein (CRP), leucocyte count (LC), and erythrocyte sedimentation rate (ESR) in late fracture-related infection (FRI).

Materials and Methods

PubMed, Embase, and Cochrane databases were searched focusing on the diagnostic value of CRP, LC, and ESR in late FRI. Sensitivity and specificity combinations were extracted for each marker. Average estimates were obtained using bivariate mixed effects models.


Bone & Joint Research
Vol. 7, Issue 7 | Pages 447 - 456
1 Jul 2018
Morgenstern M Vallejo A McNally MA Moriarty TF Ferguson JY Nijs S Metsemakers W

Objectives

As well as debridement and irrigation, soft-tissue coverage, and osseous stabilization, systemic antibiotic prophylaxis is considered the benchmark in the management of open fractures and considerably reduces the risk of subsequent fracture-related infections (FRI). The direct application of antibiotics in the surgical field (local antibiotics) has been used for decades as additional prophylaxis in open fractures, although definitive evidence confirming a beneficial effect is scarce. The purpose of the present study was to review the clinical evidence regarding the effect of prophylactic application of local antibiotics in open limb fractures.

Methods

A comprehensive literature search was performed in PubMed, Web of Science, and Embase. Cohort studies investigating the effect of additional local antibiotic prophylaxis compared with systemic prophylaxis alone in the management of open fractures were included and the data were pooled in a meta-analysis.


The Bone & Joint Journal
Vol. 100-B, Issue 7 | Pages 966 - 972
1 Jul 2018
Morgenstern M Athanasou NA Ferguson JY Metsemakers W Atkins BL McNally MA

Aims

This study aimed to investigate the role of quantitative histological analysis in the diagnosis of fracture-related infection (FRI).

Patients and Methods

The clinical features, microbiology culture results, and histological analysis in 156 surgically treated nonunions were used to stratify the likelihood of associated infection. There were 64 confirmed infected nonunions (one or more confirmatory criteria: pus, sinus, and bacterial growth in two or more samples), 66 aseptic nonunions (no confirmatory criteria), and 26 possibly infected nonunions (pathogen identified from a single specimen and no confirmatory criteria). The histological inflammatory response was assessed by average neutrophil polymorph (NPs) counts per high-power field (HPF) and compared with the established diagnosis.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_8 | Pages 2 - 2
1 May 2018
Morgenstern M Athanasou NA Ferguson JY Metsemakers W Atkins BL McNally MA
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Aim

The aim was to investigate the value of quantitative histological analysis in the diagnosis of fracture-related infection (FRI).

Patients and Methods

The clinical features, microbiology culture results and histological analysis in 156 surgically treated non-unions were used to stratify the likelihood of associated infection. There were 64 confirmed infected non-unions (≥1 confirmatory criteria; pus, sinus and bacterial growth in ≥2 samples), 66 aseptic non-unions (no confirmatory criteria) and 26 possibly infected (pathogen identified from a single specimen and no confirmatory criteria). The histological inflammatory response was assessed by average neutrophil polymorphs (NPs) counts per high power field (HPF) and compared to the established diagnosis.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_22 | Pages 63 - 63
1 Dec 2017
Pützler J Arens D Metsemakers W Zeiter S Richard K Richards G Raschke M Moriarty F
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Aim

Open fractures still have a high risk for fracture-related Infection (FRI). The optimal duration of perioperative antibiotic prophylaxis (PAP) for open fractures remains controversial due to heterogeneous guidelines and highly variable prophylactic regimens in clinical practice. In order to provide further evidence with which to support the selection of antibiotic duration for open fracture care, we performed a preclinical evaluation in a contaminated rabbit fracture model.

Method

A complete humeral osteotomy in 18 rabbits was fixed with a 7-hole-LCP and inoculated with Staphylococcus aureus (2×106 colony forming units, CFU per inoculum). This inoculum was previously shown to result in a 100% infection rate in the absence of any antibiotic prophylaxis. Cefuroxime was administered intravenously in a weight adjusted dosage equivalent to human medicine (18.75 mg/kg) as a single shot only, for 24 hours (every 8 hours) and for 72 hours (every 8 hours) in separate groups of rabbits (n=6 per group). Infection rate per group was assessed after two weeks by quantitative bacteriological evaluation of soft tissue, bone and implants. Blood samples were taken from rabbits preoperatively and on days 3, 7 and 14 after surgery to measure white blood cell count (WBC) and C-reactive protein (CRP) levels.