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Bone & Joint Open
Vol. 4, Issue 3 | Pages 146 - 157
7 Mar 2023
Camilleri-Brennan J James S McDaid C Adamson J Jones K O'Carroll G Akhter Z Eltayeb M Sharma H

Aims

Chronic osteomyelitis (COM) of the lower limb in adults can be surgically managed by either limb reconstruction or amputation. This scoping review aims to map the outcomes used in studies surgically managing COM in order to aid future development of a core outcome set.

Methods

A total of 11 databases were searched. A subset of studies published between 1 October 2020 and 1 January 2011 from a larger review mapping research on limb reconstruction and limb amputation for the management of lower limb COM were eligible. All outcomes were extracted and recorded verbatim. Outcomes were grouped and categorized as per the revised Williamson and Clarke taxonomy.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_2 | Pages 3 - 3
10 Feb 2023
Sundaram A Woods J Clifton L Alt V Clark R Carey Smith R
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Complex acetabular reconstruction for oncology and bone loss are challenging for surgeons due to their often hostile biological and mechanical environments. Titrating concentrations of silver ions on implants and alternative modes of delivery allow surgeons to exploit anti-infective properties without compromising bone on growth and thus providing a long-term stable fixation. We present a case series of 12 custom acetabular tri-flange and custom hemipelvis reconstructions (Ossis, Christchurch, New Zealand), with an ultrathin plasma coating of silver particles embedded between layers of siloxane (BioGate HyProtect™, Nuremberg, Germany).

At the time of reporting no implant has been revised and no patient has required a hospital admission or debridement for a deep surgical site infection. Routine follow up x-rays were reviewed and found 2 cases with loosening, both at their respective anterior fixation. Radiographs of both cases show remodelling at the ilium indicative of stable fixation posteriorly. Both patients remain asymptomatic. 3 patients were readmitted for dislocations, 1 of whom had 5 dislocations within 3 weeks post-operatively and was immobilised in an abduction brace to address a lack of muscle tone and has not had a revision of their components.

Utilising navigation with meticulous implant design and construction; augmented with an ultrathin plasma coating of silver particles embedded between layers of siloxane with controlled and long-term generation of silver ion diffusion has led to outstanding outcomes in this series of 12 custom acetabular and hemipelvis reconstructions. No patients were revised for infection and no patients show signs of failure of bone on growth and incorporation. Hip instability remains a problem in these challenging mechanical environments and we continue to reassess our approach to this multifaceted problem.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 87 - 87
1 Dec 2018
Mouton W Diot A Trouillet-Assant S Josse J Caillon J Bouvard D Jacqueline C Laurent F
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Aim. Staphylococcus aureus (SA) chronic bone and joint infections (BJI) are characterized by a progressive destruction of bone tissue associated to SA persistence which results in a large number of relapses (10–20%). The main factors proposed for these failures are: i) a weak diffusion of antibiotics in bone tissue, ii) formation of biofilm, iii) the bacterial internalization by the cells responsible for bone mineralization, namely the osteoblasts (OB). Our in vitro and in vivo work aimed at providing new information on the impact of SA, more specifically of internalized SA, on bone homeostasis. Method. Effect of SA infection (8325–4/FnBP+; DU5883/FnBP-) on the viability, differentiation and mineralization of an OB cell line was measured in vitro by MTT and Phosphatase Alcaline (PAL) activity assays and quantification of calcium deposits using Alizarin red, respectively. A gentamicin protection assay (GPA) confirmed that the effects observed are due solely to the internalized SA. In vivo, X-ray microtomography (μCT) and 3D reconstruction was used to evaluate the impact of SA infection on bone formation and bone resorption in a mouse model of femur infection. Results. In vitro, the infection of pre-OB decreases their capacity of differentiation into mature OB displaying a PAL activity. This effect depends on both the multiplicity of infection and invasion capacities of the strains used (8325–4 (invasion competent) vs DU5883 (invasion incompetent)). The infection delays mineralization after 5 days (p <0.0001), likely due to a cytotoxic effect. Indeed, after bacterial clearance at J21, this delay is made up (no difference between infected and uninfected cells). These results are consistent with the preliminary in vivo observations (μCT) showing a significant decrease in the thickness of trabecular of infected femurs with 8325–4 compared to DU5883 and non-infected femurs (p< 0, 0041). Conclusions. These results suggest that the internalization of SA leads to an imbalance of bone remodeling, in particular by a cytotoxic effect on the pre-OB and a slowed-down formation of bone tissue by OB, leading to a significant bone loss. The ongoing study of the cellular and bacterial mechanisms involved in this internalization should allow a better management of chronic BJI


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 51 - 51
1 Dec 2018
Papadia D Odorizzi G Buccelletti F Bertoldi L
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Aim

The optimal treatment of displaced intra-articular calcaneal fractures (DIACF) remains controversial. The operative treatment group has better anatomical recovery, functional outcome scores and less pain than non operative treatment patients, but it may lead to a higher incidence of complications, such as delayed wound healing and surgical site infections. The aim of this study was to analyze the prophylactic effect using a biphasic bone substitute (BS) eluting antibiotic on calcaneal implant-related infections.

Methods

We conducted a retrospective non-randomized review of all patients with DIACF (type Sanders 2, 3, 4) from 2009 to 2017; 103 calcaneal fractures of 90 patients (13 bilaterally) were treated with plates. All cases received the same systemic antibiotic prophylaxis; BS was used on more complex cases with large bone defect and BS was added with antibiotic on higher risk patients. We collected data including complications: major (deep infections, osteomyelitis) and minor complications (wound dehiscence, superficial infection). We considered the absence of deep infections after 6 months. We compared statistically the outcomes of 3 operative groups: the first was treated with plates only (A), the second with plates and BS (B) and the third with plates added with BS eluting antibiotic (vancomicine or gentamicine) (C).


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 28 - 28
1 Oct 2022
Mannala G Rupp M Alt V
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Aim. Galleria mellonella larvae is a well-known insect infection model that has been used to test the virulence of bacterial and fungal strains as well as for the high throughput screening of antimicrobial compounds against infections. Recently, we have developed insect infection model G. mellonella larvae to study implant associated biofilm infections using small K-wire as implant material. Here, we aimed to further expand the use of G. mellonella to test other materials such as bone cement with combination of gentamicin to treat implant-associated infections. Method. The poly methyl methacrylate (PMMA) with and without gentamicin and liquid methyl methacrylate (MMA) were kindly provided by Heraeus Medical GmbH, Wehrheim. To make the bone cement implants as cubes, Teflon plate (Karl Lettenbauer, Erlangen) with specified well size was used. The Radiopaque polymer and monomer were mixed well in a bowl, applied over on to the Teflon plate and pressed with spatula to form fine and uniform cubes. After polymerization, the bone cement implants were taken out of the Teflon well plate with the help of pin. For the infection process, bone cement cubes were pre-incubated with S. aureus EDCC 5055 culture at 5×10. 6. CFU/ml for 30 min at 150 rpm shaking conditions. Later, these implants were washed with 10ml PBS and implanted in the larvae as mentioned. Survival of the larvae were observed at 37°C in an incubator. To analyze the susceptibility of the bacterial infections towards gentamicin, survival of the larvae compared with control group implanted only with bone cement. The effect of gentamicin was also measured in terms of S. aureus load in larvae on 2. nd. day. SEM analysis was performed to see the effect of gentamicin on biofilm formation on bone cement. Results. Our experiments established the G. mellonella as an excellent model to screen bone cement with antimicrobial compounds against bacterial infections. The gentamicin bone cement samples showed excellent S. aureus bacterial load reduction after the implantation in G. mellonella model. The bone cement with gentamicin showed better survival of larvae infected with S. aureus compared to control. Finally, the gentamicin also affected the biofilm formation on the bone cement surface with S. aureus. Conclusions. Thus, our work showed G. mellonella is a rapid, cheap economical pre-clinical model to study the bone cement associate bacterial infections as well as screening of the various antimicrobial compounds


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_15 | Pages 35 - 35
7 Nov 2023
Tsang J Epstein G Ferreira N
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The Cierny and Mader classification assists with decision-making in the management of osteomyelitis by strafying the host status and the pathoanatomy of disease. However the anatomical type IV represents a heterogenous group with regards to treatment requirements and outcomes. We propose that modification of the Cierny and Mader anatomical classification with an additional type V classifier (diffuse corticomedullary involvement with an associated critical bone defect) will allow more accurate stratification of patients and tailoring of treatment strategies. A retrospective review of 83 patients undergoing treatment for Cierny and Mader anatomical type IV osteomyelitis of the appendicular skeleton at a single centre was performed. Risk factors for the presence of a critical bone defect were female patients (OR 3.1 (95% CI 1.08– 8.92)) and requirement for soft tissue reconstruction (OR 3.35 (95% CI 1.35–8.31)); osteomyelitis of the femur was negatively associated with the presence of a critical bone defect (OR 0.13 (95% CI 0.03–0.66)). There was no statistical significant risk of adverse outcomes (failure to eradicate infection or achieve bone union) associated with the presence of a critical-sized bone defect. The median time to bone union was ten months (95% CI 7.9–12.1 months). There was a statistically significant difference in the median time to bone union between cases with a critical bone defect (12.0 months (95% 10.2–13.7 months)) and those without (6.0 months (95% CI 4.8–7.1 months)). This study provided evidence to support the introduction of a new subgroup of the Cierny and Mader anatomical classification (Type V). Using a standardised approach to management, comparable early outcomes can be achieved in patients with Cierny and Mader anatomical type V osteomyelitis. However, to achieve a successful outcome, there is a requirement for additional bone and soft tissue reconstruction procedures with an associated increase in treatment time


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_15 | Pages 38 - 38
7 Nov 2023
Mdingi V Maré P Marais L
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Paediatric bone and joint infections remain common in low- and middle-income countries (LMICs). We aimed to determine the complication rate and incidence of disseminated infection in paediatric bone and joint infections in an LMIC setting. Secondly, we aimed to elucidate factors associated with complications and disseminated disease. We retrospectively reviewed our database for children that presented with bone and joint infections between September 2015 and March 2019. Data were extracted to identify factors that were associated with development of complications and disseminated infection. We analysed 49 children. The median age at presentation was 6 years (range 1 month to 12 years). Locally advanced disease was present in 13 children (27%). The remaining 36 children were evenly divided (18/49 each, 37%) between isolated AHOM and SA, respectively. Disseminated disease was present in 16 children (33%) and was associated with locally advanced disease, an increase in number of surgeries and an increased length of stay. Twenty-six complications were documented in 22 (45%) children. Chronic osteomyelitis developed in 15/49 (31%) cases, growth arrest in 5/49 (10%), and pathological fracture, DVT and septic shock in 2/49 (4%) each. Complicated disease was associated with locally advanced disease, a higher number of surgeries, disseminated disease and an increased length of stay. Sixty five percent of cases cultured Staphylococcus aureus, while 25% (12/49) were culture negative. The median time from admission to surgery was one day, and the median time from onset of symptoms to surgery was seven days. We found a high complication rate. One third of patients had locally advanced disease, and this was associated with the development of complications and disseminated disease. Further studies are needed to be able to predict which children will have poor outcomes


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_5 | Pages 2 - 2
23 Apr 2024
Tsang SJ Epstein G Ferreira N
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Introduction. The Cierny and Mader classification assists with decision-making by stratifying host status and the pathoanatomy of the disease. However, the anatomical type IV represents a heterogenous group with regards to treatment requirements and outcomes. We propose that modification of the Cierny and Mader anatomical classification with an additional type V classifier (diffuse corticomedullary involvement with an associated critical bone defect) will allow more accurate stratification of patients and tailoring of treatment strategies. Materials & Methods. A retrospective review of 83 patients undergoing treatment for Cierny and Mader anatomical type IV osteomyelitis of the appendicular skeleton at a single centre was performed. Results. Risk factors for the presence of a critical bone defect were female patients (OR 3.1 (95% CI 1.08–8.92)) and requirement for soft tissue reconstruction (OR 3.35 (95% CI 1.35–8.31)); osteomyelitis of the femur was negatively associated with the presence of a critical bone defect (OR 0.13 (95% CI 0.03–0.66)). There was no statistically significant risk of adverse outcomes (failure to eradicate infection or achieve bone union) associated with the presence of a critical-sized bone defect. The median time to bone union was ten months (95% CI 7.9–12.1 months). There was a statistically significant difference in the median time to bone union between cases with a critical bone defect (12.0 months (95% 10.2–13.7 months)) and those without (6.0 months (95% CI 4.8–7.1 months)). Conclusions. This study provided evidence to support the introduction of a new subgroup of the Cierny and Mader anatomical classification (Type V). Using a standardised approach to management, comparable early outcomes can be achieved in patients with Cierny and Mader anatomical type V osteomyelitis. However, to achieve a successful outcome, there is a requirement for additional bone and soft tissue reconstruction procedures with an associated increase in treatment time


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 25 - 25
24 Nov 2023
Parente R Possetti V Granata V Schiavone ML Strina D Davi F Menale C Palagano E Filipović M Grčević D Bottazzi B Mantovani A Sobacchi C Inforzato A
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Aim. Osteomyelitis (OM) is a debilitating infection of the bone that originates from hematogenous spreading of microbes or contamination after surgery/fracture. OM is mainly caused by the opportunistic bacterium Staphylococcus aureus (SA), which can evade the host immune response, acquire antibiotic resistance and chronically colonize the musculoskeletal tissue . 1,2. , yet the underlying molecular and cellular processes are largely unclear. This study aimed to characterize the pathogenetic mechanisms of SA-OM with a focus on the long pentraxin 3 (PTX3), a soluble pattern recognition molecule and bone tissue component that is emerging as a new player in osteoimmunology . 3. and a diagnostic marker of periprosthetic joint infections, a common form of OM. 4. . Method. A murine model of OM based on intra-bone injection of SA was developed that closely mimicked surgery/trauma-related OM in humans and allowed addressing the role of PTX3 in gene-modified (Ptx3-/-) animals. Local and systemic infection and inflammation were assessed via microbiology, flow cytometry, histochemistry and microCT techniques. Results. SA-injected mice developed chronic infection with measurable levels of viable bone-resident bacteria up until 30 days from microbial challenge. The infection was confined to the treated limbs only and accompanied by extensive tissue remodelling. The bacterial load was higher in WT than Ptx3. -/-. animals at 6 and 14 days from SA injection. Accordingly, WT mice had enhanced systemic inflammation with expanded innate immune compartment in the spleen and increased serum levels of inflammatory cytokines and chemokines. PTX3 levels were higher in SA- than vehicle (PBS)-injected WT animals both in the serum and bone tissue. Furthermore, administration of a PTX3-targeting antibody reduced the bacterial burden in the bones of SA-injected WT mice. Conclusions. In a mouse model of SA-OM, genetic deficiency of PTX3 protected from infection and inflammation, pointing to this pentraxin as a crucial player in OM pathogenesis and a novel therapeutic target in bone infections. The study was approved by the Italian Ministry of Health (approval n. 520/2019-PR issued on 19/07/2019) and supported by Fondazione Beppe and Nuccy Angiolini


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 79 - 79
24 Nov 2023
Puetzler J Vallejo A Gosheger G Schulze M Arens D Zeiter S Siverino C Moriarty F
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Aim. The time to onset of symptoms after fracture fixation is still commonly used to classify fracture-related infections (FRI). Early infections (<2 weeks) can often be treated with debridement, systemic antibiotics, irrigation, and implant preservation (DAIR). Late infections (>10 weeks) typically require implant removal as mature, antibiotic-tolerant biofilms have formed. However, the recommendations for delayed infections (2–10 weeks) are not clearly defined. Here, infection healing and bone healing in early and delayed FRI is investigated in a rabbit model with a standardized DAIR procedure. Method. Staphylococcus aureus was inoculated into 17 rabbits after plate osteosynthesis in a humerus osteotomy. The infection developed either one week (early group, n=6) or four weeks (delayed group, n=6) before a standardized DAIR procedure and microbiological analysis were performed. Systemic antibiotics were administered for six weeks (two weeks: Nafcillin+Rifampin, four weeks: Levofloxacin+Rifampin). A control group (n=5) also underwent a revision operation (debridement and irrigation) after four weeks, but received no antibiotic treatment. Rabbits were euthanized seven weeks after the revision operation. Bone healing was assessed using a modified radiographic union score for tibial fractures (mRUST). After euthanasia, a quantitative microbiological examination of the entire humerus, adjacent soft tissues, and implants was performed. Results. All animals were infected at the time of revision surgery, with the bacterial load in the early group (especially in soft tissues) being greater than in the delayed group and control group. This indicates infiltration of bacteria into areas that are more difficult to reach after four weeks of debridement. The infection was eradicated in all animals in both the early and delayed groups at euthanasia, but not in the control group (CFU median (IQR): 2.1×10. 7. (1.3×10. 7. -2.6×10. 7. ). The osteotomy healed in the early group, while bone healing was significantly impaired in both the delayed group and control group (mRUST median (IQR): early group: 16 (14–16), delayed group: 7.5 (6–10), control: 7 (5.5–9); early vs. delayed: p=0.0411, early vs. control p=0.0065). Conclusion. The maturation of the infection between the first and fourth week does not affect the success of infection eradication in this rabbit FRI model. However, bone healing appears to be impaired with increasing duration of infection


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 78 - 78
1 Oct 2022
Cacciola G Bruschetta A Meo FD Cavaliere P
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Aim. The primary endpoint of this study is to characterize the progression of bone defects at the femoral and tibial side in patients who sustained PJI of the knee that underwent two-stage revision with spacer implantation. In addition, we want to analyze the differences between functional moulded and hand-made spacers. Methods. A retrospective analysis of patients that underwent two-stage revision due to PJI of the knee between January 2014 and December 2021 at our institution. Diagnosis of infection was based on the criteria of the Muscoloskeletal Infection Society. The bone defect evaluation was performed intraoperatively based on the AORI classification. The basal evaluation was performed at the time the resection arthroplasty and spacer implantation surgery. The final evaluation was performed at the second-stage surgery, at the time of spacer removal and revision implant positioning. The differences between groups were characterized by using T-test student for continuous variables, and by using chi-square for categorical variables. A p-value < 0.05 was defined as significant. Results. Complete data of 37 two-stage TKAs revision were included in the study. An articulating moulded functional spacer was used in 14 (35.9%) cases, while a hand-made spacer was used in 23 (58.9%) cases. The average length of interval period (excluding the time for patients that retained the spacer) was 146.6 days. A bone defects progression based on the AORI classification was documented in 24 cases at the femoral side (61.6%), a bone defect progression was documented in 17 cases at the tibial side (43.6%), and a bone defect at both sides was documented in 13 cases (33.3%). A statistically significant greater bone defect progression at the tibial side was observed when hand-made spacers were used. A complication during the interval period was reported in five cases (12.8%) and postoperative complication was reported in 9 cases (23.1%). Conclusions. When comparing patients in which a functional articulating spacer was used, with patients in which static spacer was used, we reported a statistically significant reduced bone defect progression during the interval period at the femoral side only when moulded spacers were used. We observed a higher incidence of bone defect progression also at the tibial and both sides when hand-made spacers were used. This is the first study that documented the bone defect progression during two-stage revision of the knee, the results observed in this study are very encouraging


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. Results. A total of 120 patients were included, of whom 70 DAIR patients and 50 non-DAIR patients. Within a median follow-up of 35.5 months, 21.4% of DAIR patients developed a recurrent FRI compared to 12.0% of non-DAIR patients. The DAIR procedure was successful in 45 patients (64.3%). According to the Willenegger and Roth classification, DAIR success was achieved in 66.7% (n=16/24) of patients with an early infection (<2 weeks), 64.4% (n=29/45) of patients with a delayed infection (2–10 weeks) and 0.0% (0/1) of patients with a late infection (>10 weeks). Univariate analysis showed that the duration of infection was not associated with DAIR success in this cohort (p=0.136; OR: 0.977; 95%CI: [0.947–1.007]). However, an appropriate antimicrobial regimen was associated with success of DAIR (p=0.029; OR: 3.231; 95%CI: [1.138–9.506]). Conclusions. Although the results should be interpreted with caution, an increased duration of infection was not associated with a decreased success rate of a DAIR procedure in patients with FRI of the lower leg. The results of this study highlight the multifactorial contribution to the success of a DAIR procedure and emphasize the importance of adequate antimicrobial treatment. Therefore, time to surgery should not be the only key-factor when considering a DAIR procedure to treat FRI


The Bone & Joint Journal
Vol. 106-B, Issue 6 | Pages 632 - 638
1 Jun 2024
Hart CM Kelley BV Mamouei Z Turkmani A Ralston M Arnold M Bernthal NM Sassoon AA

Aims. Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation. Methods. A mouse model of PJI of the knee was used. Mice were randomized into groups with intervention at the time of surgery (postoperative day (POD) 0): a sterile control (SC; n = 6); infected control (IC; n = 15); systemic vancomycin (SV; n = 9); vancomycin powder (VP; n = 21); and vancomycin bead (VB; n = 19) groups. Delayed inoculation was introduced during an arthrotomy on POD 7 with 1 × 10. 5. colony-forming units (CFUs) of a bioluminescent strain of Staphylococcus aureus. The bacterial burden was monitored using bioluminescence in vivo. All mice were killed on POD 21. Implants and soft-tissue were harvested and sonicated for analysis of the CFUs. Results. The mean in vivo bioluminescence in the VB group was significantly lower on POD 8 and POD 10 compared with the other groups. There was a significant 1.3-log. 10. (95%) and 1.5-log. 10. (97%) reduction in mean soft-tissue CFUs in the VB group compared with the VP and IC groups (3.6 × 10. 3. vs 7.0 × 10. 4. ; p = 0.022; 3.6 × 10. 3. vs 1.0 × 10. 5. ; p = 0.007, respectively) at POD 21. There was a significant 1.6-log. 10. (98%) reduction in mean implant CFUs in the VB group compared with the IC group (1.3 × 10. 0. vs 4.7 × 10. 1. , respectively; p = 0.038). Combined soft-tissue and implant infection was prevented in 10 of 19 mice (53%) in the VB group as opposed to 5 of 21 (24%) in the VP group, 3 of 15 (20%) in the IC group, and 0% in the SV group. Conclusion. In our in vivo mouse model, antibiotic-releasing calcium sulphate beads appeared to outperform vancomycin powder alone in lowering the bacterial burden and preventing soft-tissue and implant infections. Cite this article: Bone Joint J 2024;106-B(6):632–638


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. Results. Lead antimicrobial agents were soluble in high concentrations and were stable in CarboCell formulations. Three combinations completely eradicated bacteria in the in vitro semi-solid biofilm model. In the rat osteomyelitis model, CarboCell formulations of the lead combinations also eradicated bacteria in bone and implant in several rats and significantly reduced infection in all treated rats. In the pig model, CarboCell antimicrobial monotherapy demonstrated promising therapeutic efficacy, including complete eradication of infection in bone and implants in several pigs and significantly reduced bacterial burden in others. Conclusions. Using the CarboCell technology for antimicrobial delivery exert substantial loco-regional efficacy. The attractive sustained high-dose antibiotic release profile combined with the flexible injection technology allows surgeons to accurately place effective drug-eluting depots in key areas not accessible to competing technologies


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 58 - 58
24 Nov 2023
Yates TA Vahesan O Warren S Scobie A
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Aim. At our tertiary orthopaedic centre, mycobacterial cultures are routinely performed on bone and joint samples sent for bacterial culture. We have previously described the prevalence Mycobacterium tuberculosis Complex (MTBC) in these samples. Here, we describe the prevalence of non-tuberculous mycobacteria (NTM). We calculate the number needed to test to identify one previously undiagnosed mycobacterial bone or joint infection. Methods. Samples taken during a single procedure were pooled in one BACTEC MGIT culture. From laboratory records, we ascertained the number of mycobacterial cultures performed, the number positive for MTBC or NTM, and characteristics of individuals from whom mycobacteria were isolated. We collected the same data from 100 individuals with negative mycobacterial cultures. Results presented here are from interim analysis. Results. Excluding sample types that were clearly not bone or joint samples, 6162 mycobacterial cultures were performed between 4 July 2017 and 30 September 2022. Twenty-two patients had MTBC and 6 patients had NTM newly isolated from bone or joint samples placed in mycobacterial culture, with a further patient having both M. tuberculosis and M. avium isolated. In both patients with M. abscessus, the organism also grew in routine bacterial cultures. In one further patient, M. fortuitum was isolated from a sample not put into mycobacterial culture. To identify one new mycobacterial infection of bone or joint (MTBC or NTM) that would not be detected with routine bacterial cultures, 228 (95% CI 157 – 346) mycobacterial cultures were needed. The laboratory cost per additional patient identified using MGIT cultures was €12,540 (95% CI €8,635 - €19,030). Mycobacterial cultures were much less likely to be positive in samples taken from prosthetic joints. They were more likely to be positive in spinal samples and in samples taken from patients with suspected sarcoma. In patients for whom we had contemporaneous histological specimens, these demonstrated granulomatous inflammation in 86% (18/21) of patients from whom MTBC had been isolated but in neither of the two patients from whom only NTM was isolated. Ascertaining the clinical significance of NTM isolates is challenging, although in 2/8 cases the same organism was isolated following repeat sampling. Conclusions. Targeted rather than routine mycobacterial culture of bone and joint specimens should be considered in settings with a low burden of tuberculosis. NTM are rarely isolated from bone and joint specimens at our centre and fast growers may be isolated using routine bacterial culture


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 16 - 16
24 Nov 2023
Siverino C Gens L Ernst M Buchholz T Windolf M Richards G Zeiter S Moriarty F
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Aim. Debridement, Antibiotics, Irrigation, and implant Retention (DAIR) is a surgical treatment protocol suitable for some patients with fracture related infection (FRI). Clinically relevant pre-clinical models of DAIR are scarce and none have been developed in large animals. Therefore, this project aimed to develop a large animal model for FRI including a DAIR approach and compare outcomes after 2 or 5 weeks of infection. Method. Swiss Alpine sheep (n=8), (2–6 years, 50–80 kg) were included in this study. This study was approved by cantonal Ethical authorities in Chur, Switzerland. A 2 mm osteotomy was created in the tibia and fixed with a 10-hole 5.5 mm steel plate. Subsequently, 2.5 mL of saline solution containing 10. 6. CFU/mL of Staphylococcus aureus MSSA (ATCC 25923) was added over the plate. Sheep were observed for 2 (n=3) or 5 weeks (n=5) until revision surgery, during which visibly infected or necrotic tissues were removed, and the wound flushed with saline. All samples were collected for bacterial quantification. After revision surgery, the sheep were treated systemically for 2 weeks with flucloxacillin and for 4 weeks with rifampicin and cotrimoxazole. After 2 further weeks off antibiotics, the animals were euthanized. Bacteriological culture was performed at the end of the study. Bone cores were isolated from the osteotomy site and processed for Giemsa & Eosin and Brown and Brenn staining. A radiographical examination was performed every second week. Results. Bacteriological evaluation of the retrieved samples during revision surgery showed no significant difference between the 2 vs 5 weeks infection periods in term of total CFU counts. At the end of the study, radiographical examination showed callus formation over the osteotomy site in both groups, although the osteotomy was not completely healed in either group. At euthanasia, the 2 weeks infection group showed a higher soft tissue burden compared to the 5 weeks group, whereby the infection in the 5 weeks group was primarily located in the bone and bone marrow. Conclusions. The large animal model of FRI and DAIR was successfully established. Bacteriological outcomes highlight that the increasing duration of the infection does not change the outcome but the location of the infection from a predominantly soft tissue infection to a deeper bone and intramedullary (IM) channel infection. The debridement of the IM channel could potentially reduce the infection burden by eliminating those bacteria not easily reached by systemic antibiotics, though is not practical using conventional techniques


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_5 | Pages 43 - 43
1 Apr 2022
Clesham K Storme J Donnelly T Wade A Meleady E Green C
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Introduction. Hip arthrodiastasis for paediatric hip conditions such as Perthes disease is growing in popularity. Intended merits include halting the collapse of the femoral head and maintaining sphericity by minimising the joint reaction force. This can also be applied to protecting hip reconstruction following treatment of hip dysplasia. Our aim was to assess functional outcomes and complications in a cohort of paediatric patients. Materials and Methods. A retrospective single-surgeon cohort study was performed in a University teaching hospital from 2018–2021. Follow-up was performed via telephone interview and review of patient records. Complications, time in frame and functional scores using the WOMAC hip score were recorded. Results. Following review, 26 procedures were identified in 24 patients. Indications included 16 cases of Perthes disease, 4 following slipper upper femoral epiphysis, 3 avascular necrosis, and single cases following infection, dysplasia and a bone cyst. Pre-treatment WOMAC scores averaged 53.9, improving to 88.5 post-removal. Pin site infections were encountered in 11 patients, all treated with oral antibiotics. Two patients required early removal of frame due to pin loosening. Average time in frame was 3.9 months. Conclusions. This series displays how hip arthrodiastasis can be used to manage paediatric hip conditions. Complex reconstructions may be required in patients with severe deformity following perthes disease, DDH or SUFE. The use of arthrodiastasis in these patients aims to protect the reconstruction and potentially improve outcomes. A dedicated team of specialist nurses, physiotherapists and psychologists are crucial to the treatment program


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_6 | Pages 3 - 3
1 May 2021
Lahoti O Abhishetty N Shetty S
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Introduction. Charcot Arthropathy related foot and ankle deformities are a serious challenge. Surgical treatment of these deformities is now well established. The traditional surgical method of extensive surgical exposure, excision of bone, acute correction and internal fixation is not always appropriate in presence of active ulceration, deep infection and poor bone quality. Minimally invasive osteotomies and gradual correction of deformities with a circular frame are proving helpful in minimizing complications. We present our experience with the use of Taylor Spatial Frame (TSF) in 10 patients with recurrent ulceration and deformity. Materials and Methods. Our indication for the treatment with TSF is recurrent or intractable ulceration with or without active bone infection or a history of infection in a deformed foot and/or ankle. There are 2 female and 8 male patients in this cohort. We used a long bone module for ankle and hindfoot deformities (3 patients) and a forefoot 6×6 butt frame (7 patients) for midfoot deformities. An osteotomy through midfoot was performed in all chronic stable midfoot deformity cases and a calcaneal osteotomy and gradual correction through ankle in when hindfoot and ankle deformities co-existed. Results. Our outcome measures are a complete healing of ulcer and infection without recurrence, clinically plantigrade foot and ability to wear regular shoes or diabetic footwear. We achieved this outcome in 9 out of 10 patients. Successful patients remain ulcer free at minimum 7 and maximum 14 years follow up. Complications included eight episodes of pin infection that responded to oral antibiotics only and two pin breakages. Conclusions. Our results confirm that Taylor Spatial Frame treatment is a good alternative to traditional surgery in high-risk complex Charcot neuroarthropathy foot and ankle deformities


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 75 - 75
1 Dec 2021
Carrasco FC Karbysheva S Pérez-Prieto D Margaryan D Barbera OF Trampuz A Garcia JCM
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Aim. Quadrupled hamstring anterior cruciate ligament plasties (4xHp) have been described as having a higher risk of infection than bone patellar tendon bone plasties (BPTBp). There are 2 theories that might explain this phenomenon. One is the presence of sutures in a 4xHp that could act as a foreign body, The other is the more complex preparation of a 4xHp that might lead to higher contamination rates during the process. The objective of the present study was to evaluate the formation of biofilm in these plasties and to compare it between a 4xHp and a BPTBp. The hypothesis was that the presence of sutures in 4xHp would increase the amount of biofilm present in them in comparison to BPTBp. Method. A descriptive in vitro study was conducted. One 4xHp and one BPTBp were prepared. They were subsequently divided into 8 fragments. Three of them were reserved for negative control, and the rest were contaminated with a strain of S. Epidermidis (ATCC 35984) 10–5. Finally, a quantitative analysis was carried out by means of microcalorimetry and sonication with plating. Additionally, a qualitative analysis was carried out by means of electron microscopy. Results. In isothermal microcalorimetry, both contaminated plasties showed the same growth dynamics with a population peak (200uW) at 8h. No significant differences were found between the bacterial growth profiles of 4xHp and BPTBp. The product of sonication was plated and the number of colony forming units per milliliter (CFU/ml) was counted at 24 hours. No significant differences were detected between the 4×Hp (mean +/− sem = 3,5×107 +/− 3450000) and the BPTBp (4,6 ×107 +/− 1,455e+7). With a p value of 0.6667, there were no differences of significance (Mann-Whitney test). In the samples analyzed with electron microscopy, no specific biofilm growth pattern was identified upon comparing BPTBp with 4xHp. Conclusions. There were no significant differences at either the quantitative or qualitative level when comparing bacterial growth in BPTBp and 4xHp. Therefore, the presence of sutures in 4xHp cannot be established as a predisposing factor to higher infection rates. These findings may be justified in the sense that the plasties themselves already behave like foreign bodies. Therefore, the presence of sutures does not increase the possibility of biofilm forming on their surface


The Bone & Joint Journal
Vol. 104-B, Issue 9 | Pages 1095 - 1100
1 Sep 2022
McNally MA Ferguson JY Scarborough M Ramsden A Stubbs DA Atkins BL

Aims

Excision of chronic osteomyelitic bone creates a dead space which must be managed to avoid early recurrence of infection. Systemic antibiotics cannot penetrate this space in high concentrations, so local treatment has become an attractive adjunct to surgery. The aim of this study was to present the mid- to long-term results of local treatment with gentamicin in a bioabsorbable ceramic carrier.

Methods

A prospective series of 100 patients with Cierny-Mader Types III and IV chronic ostemyelitis, affecting 105 bones, were treated with a single-stage procedure including debridement, deep tissue sampling, local and systemic antibiotics, stabilization, and immediate skin closure. Chronic osteomyelitis was confirmed using strict diagnostic criteria. The mean follow-up was 6.05 years (4.2 to 8.4).