Antibiotic-laden bone cement is an important strategy of treatment for an established bone infection. It was aimed to find the safe antibiotic dose intervals of the antibiotic cements soaked in Phosphate Buffered Saline solution and to determine whether there was a difference in terms of mechanical strength between the prepared samples.

This study was done in our institute Microbiology and Metallurgy laboratories. All samples were prepared using manual mixing technique using 40 g radiopaque Biomet® Bone cement (Zimmer Biomet, Indiana, USA) under sterile conditions at 19 ± 2 ºC.

In this study, vancomycin (4 groups − 0.5, 2, 4, 6 g), teicoplanin (4 groups − 0.8, 1.2, 2, 2.4 g), daptomycin (4 groups − 1, 2, 2.5, 3 g), piperacillin-tazobactam (4 groups − 0.125, 0.5, 1, 2 g) and meropenem (4 groups − 0.5, 2, 4, 6 g) were measured in a assay balance and added to the cement powder. Antibiotic levels ranged from the lowest 0.625% to the highest 15%.

80×10×4 mm rectangle prism-shaped sample for mechanical measurements in accordance to ISO 5833 standart and 12×6×1 mm disc-shaped samples for microbiological assesments were used. Four sample for each antibiotic dose and control group was made. Prepared samples were evaluated macroscopically and faulty samples were excluded from the study. Prepared samples were kept in Phosphate Buffered Saline solution renewed every 24 hours at 37 ºC. At the end of 6 weeks, all samples were tested with Instron ® 3369 (Norwood Massachusetts, USA) four point bending test.

Staphylococcus aureus (ATCC 29213) strain was used for samples of antibiotics containing vancomycin, teicoplanin and daptomycin after the samples prepared for antibiotic release were maintained under sterile conditions and kept in Phosphate Buffered Saline solution as appropriate. For samples containing meropenem and piperacillin - tazobactam antibiotics, Pseudomonas aeruginosa (ATCC 27853) strain was used.

The addition of more than 5% antibiotics to the cement powder was significantly reduced mechanical strength in all groups(p <0.05) however the power of significance was changed depending on the type of antibiotic. In general, adding antibiotics with 2.5% and less for cement amount was not cause significant changes in mechanical measurements. There was a negative correlation between the increase in the amount of antibiotics mixed with cement and the durability of the cement (p: <0.001, r: −0.883 to 0.914).

In this study, especially the antibacterial effects of piperacillin-tazobactam, containing 0.25 gr and 0.5 gr antibiotic doses, were found to be low. There was no bacterial growth in all other groups for 21 days. Considering the mechanical properties of groups containing meropenem, vancomycin, daptomycin and teicoplanin, it was observed that all antibiotic cements remained above the limit value of 50 MPa in the bending test at concentrations containing 2.5% and less antibiotics. This was not achieved for the piperacillin-tazobactam group. The findings of the study showed that each antibiotic has different MPa values at different doses. Therefore, it could be concluded that not only the antibiotic dose but also the type oould change the mechanical properties. In the light of these findings, mixing more than 2.5% antibiotics in cement for the antibiotic types included in the study was ineffective in terms of antibacterial effect and mechanically reduces the durability of cement below the standard value of 50 MPa.

Introduction. Osteomyelitis is a challenge in diagnosis and treatment. 18F-FDG PET-CT provides a non-invasive tool for diagnosing and localizing osteomyelitis with a sensitivity reaching 94% and specificity reaching 100%. We aimed to assess the agreement in identifying the geographic area of infected bone and planned resection on plain X-ray versus 18F-FDG PET-CT. Materials & Methods. Clinical photos and X-rays of ten osteomyelitis patients were shown to ten consultant surgeons; they were asked to draw the area of infection and extent of planned surgical debridement; data will be compared to 18F-FDG PET-CT results. Results. We tested the agreement between the surgeons in every parameter. Regarding height, there was poor agreement between surgeons. Regarding perimeter, the ten surgeons showed low-moderate agreement. The ten surgeons showed a low-moderate agreement for circularity. Results document the variability of assessment and judgement based on plain X-rays. In comparison to PET-CT, All parameters were significantly different in favour of 18F-FDG PET-CT over X-ray (P < 0.001). Conclusions. 18F FDG PET-CT provides a three-dimensional tool for localizing the exact location of the infected bone and differentiating it from the normal bone. Thus, it could be beneficial in precise pre-operative planning and surgical debridement of chronic osteomyelitis

Aim. infected segmental bone defect (ISBD) is frequent in developing countries. The aim of this study was to assess the efficacy of the Masquelet technique in the treatment of ISBD in a low-resource setting. Patients and Method. We performed a prospective cohort study during the period from 2018 to 2022. Patients with infected bone defect of long bones were included. Management protocol consisted of two stages in all patients. The first stage consisted in debridement, tissues biopsy for microbiological culture, stabilization with external fixator and defect filling with gentamicin cement spacer. The second stage consisted of reconstruction using a cancellous bone autograft alone, or a mixture of autograft with allograft (demineralized bone matrix + tricalcium phosphate) and 1 gram of vancomycin powder. All patients were followed-up for at least one year. The results were assessed based on both objective (clinical and radiographic evaluation) and subjective (limb function and patient satisfaction) criteria. Main outcomes were bone union, reoperation and failure rates, union time, and limb function. Results. We included 31 patients in this study (80.6% men), with a median age of 35 [9 – 80] years. The tibia was affected in 12 cases and the femur in 15 cases. The median size of bone defect was 4 [1.5 – 12] cm. The most prevalent microorganisms were Klebsiella pneumoniae and Staphylococcus aureus. The mean interval between both stages was 14 (8 – 36) weeks and the median follow-up period after the second stage was 20 [12-62] months. External fixation was used in both stages in 25(80%) cases. Bone union was achieved in 26 (83.8%) patients of whom 24 without recurrence of infection, over a median time of 9 [6 – 16] months. All patients with a mixed graft (allograft and autograft) impregnated with local antibiotics achieved bone union. Two patients needed reoperation for relapse of infection between both stages, and subsequently achieved bone union without recurrence of infection. There were three cases of failure related to persistent infection or insufficient fixation stability in the second stage. Conclusions. Masquelet technique is a reliable procedure that can be safely performed in limited resources settings with satisfactory results. The mixture of autograft and allograft when available, all mixed with vancomycin seems to give promising results

Introduction. We present a case of a 49-year-old patient who initially presented in May 2020 with an open pilon fracture. Managed with initial debridement, fixation and flap - who subsequently underwent circular frame application for failure of fixation, requiring a transport to fusion frame who developed beta-haemolytic streptococcus A within the site of the proximal corticotomy. Materials & Methods. A systematic review of the literature was conducted searching EMBASE, MEDLINE and Cochrane library for all articles discussing infected bone regenerate- a paucity of information was found. Abstracts were independently reviewed by 2 authors (LH and LT). In total, there were 16 papers, and then subsequently analysed we identified two case reports regarding infected regenerate. Results. Developing an infection in a regenerate is highly rare with very few reported cases within the published literature. The literature identified risk factors for an infected regenerate, with open fracture and smoking being the two consistent factors. The open fracture deep infection rate is cited at 10% in most publications, this is at the site of the open fracture and not within the regenerate. Conclusions. Infection within the regenerate during distraction osteogenesis is highly unusual, with only two other published papers in the literature to the best of our knowledge. This should be borne in mind when managing patients with infection of unknown sources in cases of distraction osteogenesis

In chronically infected fracture non-unions, treatment requires extensive debridement to remove necrotic and infected bone, often resulting in large defects requiring elaborate and prolonged bone reconstruction. One approach includes the induced membrane technique (IMT), although the differences in outcome between infected and non-infectious aetiologies remain unclear. Here we present a new rabbit humerus model for IMT secondary to infection, and, furthermore, we compare bone healing in rabbits with a chronically infected non-union compared to non-infected equivalents. A 5 mm defect was created in the humerus and filled with a polymethylmethacrylate (PMMA) spacer or left empty (n=6 per group). After 3 weeks, the PMMA spacer was replaced with a beta-tricalcium phosphate (chronOs, Synthes) scaffold, which was placed within the induced membrane and observed for a further 10 weeks. The same protocol was followed for the infected group, except that four week prior to treatment, the wound was inoculated with Staphylococcus aureus (4×10. 6. CFU/animal) and the PMMA spacer was loaded with gentamicin, and systemic therapy was applied for 4 weeks prior to chronOs application. All the animals from the infected group were culture positive during the first revision surgery (mean 3×10. 5. CFU/animal, n= 12), while at the second revision, after antibiotic therapy, all the animals were culture negative. The differences in bone healing between the non-infected and infected groups were evaluated by radiography and histology. The initially infected animals showed impaired bone healing at euthanasia, and some remnants of bacteria in histology. The non-infected animals reached bone bridging in both empty and chronOs conditions. We developed a preclinical in vivo model to investigate how bacterial infection influence bone healing in large defects with the future aim to explore new treatment concepts of infected non-union

Serial section electron microscopy (SSEM) was initially developed to map the neural connections in the brain. SSEM eventually led to the term ‘Connectomics’ to be coined to describe process of following a cell or structure through a volume of tissue. This permits the true three-dimensionality to be appreciated and relationships between cells and structures. The purpose of this study was to utilize this methodology to interrogate S. aureus infected bone. Bone samples were harvested from mice tibia infected with S. aureus and were fixed, decalcified, and osmicated. The samples were paraffin embedded and 5-micron sections were cut to identify regions of bacterial invasion into the osteocyte-lacuna-canalicular-network (OLCN). This area was cut from the paraffin block, deparaffinized, post-fixed and reprocessed into epoxy resin. Serial sections were cut at 60nm and collected onto Kapton tape utilizing the Automated Tape-collecting Ultramicrotome (ATUMtome) system. Samples were mounted onto 4” silicon wafers and post-stained with 2% uranyl acetate followed by 0.3% lead citrate and carbon coated. A ZEISS GeminiSEM 450 scanning electron microscope fitted with an electron backscatter diffusion detector was used to image the sections. The image stack was aligned and segmented using the open-source software, VASTlite. 264 serial sections were imaged, representing approximately 40 × 45 × 15-micron (x, y, z) volume of tissue. 70% of the canaliculi demonstrated infiltration by S. aureus. This study demonstrates that SSEM can be applied to the skeletal system and provide a new solution to investigate the OLCN system. It is feasible that this methodology could be implemented to investigate why some canaliculi are resistant to colonization and potentially opens up a new direction for the prevention of chronic osteomyelitis. In order to make this a realistic target, automated segmentation methodologies utilizing machine learning must be developed and applied to the bone tissue datasets

Treatment of bone infection often includes a burdensome two-stage revision. After debridement, contaminated implants are removed and replaced with a non-absorbable cement spacer loaded with antibiotics. Weeks later, the spacer is exchanged with a bone graft aiding bone healing. However, even with this two-stage approach infection persists. In this study, we investigated whether a novel 3D-printed, antibiotic-loaded, osteoinductive calcium phosphate scaffold (CPS) is effective in single-stage revision of an infected non-union with segmental bone loss in rabbits. A 5 mm defect was created in the radius of female New Zealand White rabbits. The bone fragment was replaced, stabilized with cerclage wire and inoculated with Staphylococcus aureus (MSSA). After 4 weeks, the infected bone fragment was removed, the site debrided and a spacer implanted. Depending on group allocation, rabbits received: 1) PMMA spacer with gentamycin; 2) CPS loaded with rifampin and vancomycin and 3) Non-loaded CPS. These groups received systemic cefazolin for 4 weeks after revision. Group 4 received a loaded CPS without any adjunctive systemic therapy (n=12 group1-3, n=11 group 4). All animals were euthanized 8 weeks after revision and assessed by quantitative bacteriology or histology. Covariance analysis (ANCOVA) and multiple regression were performed. All animals were culture positive at revision surgery. Half of the animals in all groups had eliminated the infection by end of study. In a historical control group with empty defect and no systemic antibiotic treatment, all animals were infected at euthanasia. There was no significant difference in CFU counts between groups at euthanasia. Our results show that treating an osteomyelitis with segmental bone loss either with CPS or PMMA has a similar cure rate of infection. However, by not requiring a second surgery, the use of CPS may offer advantages over non-resorbable equivalents such as PMMA

Background. The treatment of chronic calcaneal osteomyelitis is a challenging and increasing problem because of the high prevalence of diabetes mellitus and operative fixation of heel fractures. In 1931, Gaenslen reported treatment of hematogenous calcaneal osteomyelitis by surgical excision through a midline, sagittal plantar incision. We have refined this approach to allow successful healing and early mobilization in a modern series of complex patients with hematogenous, diabetic, and postsurgical osteomyelitis. Methods. Twenty-eight patients (mean age 54.6 years, range 20–94) with Cierny-Mader stage IIIB chronic osteomyelitis were treated with sagittal incision and calcaneal osteotomy, excision of infected bone, and wound closure. All patients received antibiotics for at least 6 weeks, and bone defects were filled with an antibiotic carrier in 20 patients. Patients were followed for a mean of 31 months (SD 25.4). Primary outcome measures were recurrence of calcaneal osteomyelitis and below-knee amputation. Secondary outcome measures included 30-day postoperative mortality and complications, duration of postoperative inpatient stay, footwear adaptions, mobility, and use of walking aids. Results. All 28 patients had failed previous medical and surgical treatment. Eighteen patients (64%) had significant comorbidities. The commonest causes of infection were diabetes ± ulceration (11 patients), fracture-related infection (4 patients), pressure ulceration, hematogenous spread, and penetrating soft tissue trauma. The overall recurrence rate of calcaneal osteomyelitis was 18% (5 patients) over the follow-up period, of which 2 patients (7%) required a below-knee amputation. Eighteen patients (64%) had a foot that comfortably fitted into a normal shoe with a custom insole. A further 6 patients (21%) required a custom-made shoe, and only 3 patients required a custom-made boot. Conclusion. Our results show that a repurposed Gaenslen calcanectomy is simple, safe, and effective in treating this difficult condition in a patient group with significant local and systemic comorbidities

Prosthetic joint infection (PJI) is a complex disease that causes significant damage to the peri-implant tissue. Developing an animal model that is clinically relevant in depicting this disease process is an important step towards developing novel successful therapies. In this study, we have performed a thorough histologic analysis of peri-implant tissue harvested post Staphylococcus aureus (S. aureus) infection of a cemented 3D-printed titanium hip implant in rats. Sprague-Dawley rats underwent left hip cemented 3D-printed titanium hemiarthroplasty via posterior approach under general anesthesia. Four surgeries were performed for the control group and another four for the infected group. The hip joint was inoculated with 5×10. 9. CFU/mL of S. aureus Xen36 prior to capsule closure. The animals were scarified 3 weeks after infection. The femur was harvested and underwent micro-CT and histologic analysis. Hematoxylin and eosin (H&E), as well as Masson's trichrome (MT) stains were performed. Immunohistochemistry (IHC) using rabbit antibody for S. aureus was also used to localize bacterial presence within femur and acetabulum tissue . The histologic analysis revealed strong resemblance to tissue changes in the clinical setting of chronic PJI. IHC demonstrated the extent of bacterial spread within the peri-implant tissue away from the site of infection. The H&E and MT stains showed 5 main features in infected bone: 1) increased PMNs, 2) fibrovascular inflammation, 3) bone necrosis, and 4) increased osteoclasts 5) fibrosis of muscular tissue and cartilage. Micro CT data showed significantly more osteolysis present around the infected prosthesis compared to control (surgery with no infection). This is the first clinically relevant PJI animal model with detailed histologic analysis that strongly resembles the clinical tissue pathology of chronic PJI. This model can provide a better understanding of how various PJI therapies can halt or reverse peri-implant tissue damage caused by infection

Background and aim. In 2019, specific diagnostic and antibiotic treatment recommendations for diabetic foot infection (DFI) and osteomyelitis (DFO) were introduced in our institution. They include principles on numbers of biopsies to obtain for microbiological/histopathological examinations, labeling anatomic localization, and antibiotic treatment (ABT) duration based on the aforementioned findings. ABT should be stopped after complete resection of infected bone. In case of incomplete resection, treatment is continued for 4–6 weeks. Two years after the introduction of these recommendations, we investigated the degree of implementation for hospitalized patients. Method. Adult patients with DFI/DFO undergoing surgical intervention from 01/2019–12/2021 were reviewed retrospectively. Diagnostic procedures were assigned to each episode when performed ≤30 days before surgical invention. Chi-square and Mann-Whitney-U tests were performed where appropriate. Results. We included 80 patients with 117 hospital episodes and 163 surgical interventions (mean 1.5 episodes and 2 interventions per patient). The mean age was 69.6 (SD 11.5) years, 75% were male. Vascular examination and MRI were performed in 70.9% and 74.4% of episodes, respectively. Impaired perfusion and DFO were confirmed in 34.9% and 56.3%, respectively. Blood cultures were sampled in 34.2%, bacteremia detected in 7.7% with S. aureus being the most common microorganism. Biopsies were obtained in 71.8% of operations, in 90.5% of those 3–5 samples. These were sent for histological examination in 63.2% of the interventions. In 43.6% the anatomic location was labeled ‘proximal to the resection margin’. Preoperative antibiotics were administered in 41.9% of the episodes because of concomitant soft-tissue infections. The most commonly used compound was amoxicillin/clavulanate (74.4%). ABT duration varied significantly when there were signs of DFO in preoperative MRI (p=0.015). The mean duration of antibiotic therapy was 9 (IQR 5–15) days in surgically cured episodes and 40.5 (IQR 15–42) days in cases with resection margins in non-healthy bone (p<0.0001). The results were similar when analyzing treatment duration with respect to osteomyelitis in histology: 13 (IQR 8–42) versus 29 (IQR 13–42) days, respectively (p=0.026). Conclusions. The adherence to recommendations in terms of biopsy sampling was excellent, moderate for sending samples to histology and poor for labeling the anatomic location. The adherence to ABT duration was good but can be improved by shortening treatment duration for surgically cured cases. Results of preoperative MRI appear to be influential on the decision-making for treatment duration

Introduction and Objective. Management of bone loss associated with bone contamination or infection represents a double biological and clinical challenge frequent in traumatology. The advent of new biomaterials can allow a different approach in the treatment of bone gap. The purpose of this study was to evaluate the prophylactic and therapeutic effectiveness of addition of a new absorbable bone substitute (BS) eluting different antibiotics in reconstruction of bone defects after infections and fractures with soft tissue damage. Materials and Methods. We conducted a review of patients with contaminated or infected bone defects treated using a new biomaterial, a porous composite of collagen matrices and Beta tricalcium phosphate (β TCP), able to provide a long-term release of different antibiotics. We have included treatment of osteomyelitis and osteosynthesis of exposed fracture (Gustilo Anderson 1–3b) or fractures with soft tissue damage and high risk of contamination. Surgical technique included debridement filling bone defect with BS eluting antibiotics, osteosynthesis (plate, nail, external fixator, kirschner wire), soft tissue coverage, and systemic antibiotic therapy. Radiographic and clinical data including complications (wound dehiscence, superficial or deep infection, osteomyelitis) were collected. Results. We treated 25 patients (21 male, 4 female) with mean age 47 yrs. (range 21–83). The locations treated (for incidence) was: 9 femurs (7 plates, 2 nail), 7 calcanei (one bilateral), 3 tibias, 2 forearms, 2 metatarsi, 2 hands, 1 elbow. 6 patients had large bone loss. 7 patients had bone infections (4 were Cierny Madern 4); 8 patients had osteosynthesis of exposed fractures Gustilo Anderson 1–3b (9 plate, one bilateral calcaneus). 8 patients had treatment for pseudoarthrosis of exposed fractures (6 femurs, 1 forearm, 1 metatarsus) and 3 patients a prophylactic treatment for calcaneal fractures with soft tissue damage. 4 deep infection were treated with multiple surgical debridement and new filling bone defect with BS eluting antibiotic with infection eradication. We have used a combination of vancomycin and gentamicin on 15 cases, vancomycin alone on 4 cases, combination of vancomycin and amikacin on 1 case and amikacin and Linezolid in a targeted multi drug resistance. At final follow-up functional outcome was good in all cases with bone healing. Conclusions. Extensive debridement is a fundamental requisite for eradication of bone infections and contamination. Filling of the bone void with loaded bio-composite eluting diversifiable local antibiotics with synergistic anti-biofilm activity is desirable. Treatment of this bone defects are advantaged when combining his reconstruction with BS and the possibility of release high antibiotic concentration at least for 10 days. This is an important complementing prophylactic and therapeutic antimicrobial option with adjuvant role to systemic therapy that enlarges the success rate

Intro. Calcium sulphate (CS) is a recent alternative for antibiotic elution in infected bones and joints. The purpose of this study is to evaluate the use of antibiotic impregnated calcium sulphate (AICS) beads in the management of infected tibia and femur, with regards to patient outcomes and complication rates (including reinfection rate, remission rate and union rate). Methods. Searches of AMED, CINAHL, EMBASE, EMCARE, Medline, PubMed and Google Scholar were conducted in June 2020, with the mesh terms: “Calcium sulphate beads” or “Calcium sulfate beads” or “antibiotic beads” or “Stimulan” AND “Bone infection” or “Osteomyelitis” or “Debridement” AND “Tibia” or “Femur”. Risk of bias was assessed using the Risk of Bias in Non-randomised Studies of interventions (ROBINS-i) tool, and quality assessed via the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria. Results. Out of 105 relevant papers, 11 met the inclusion criteria for data extraction. Total infection recurrence rate was 6.8% (range 3.2 – 11.9%, n = 295), which was significantly lower (p < 0.001) than that of polymethylmethacrylate (PMMA; 19.6%, n = 163). Complication rates varied. The main issue regarding AICS use was wound drainage (7.9 – 33.3%), which was considerably higher in studies involving treatment of the tibia only. Studies using PMMA did not experience this issue, but there were a few incidences of superficial pin tract infection following surgery. Conclusions. AICS was consistently effective at infection eradication, despite variation in causative organism and location of bead placement. Additionally, PMMA has many inconvenient properties. AICS is therefore an attractive alternative as an adjunct in treatment of infected tibia and femur. Wound drainage rate varied and was higher in studies regarding tibial cases alone

Aim. Chronic osteomyelitis (OM) is usually treated with surgical excision of infected bone and subsequent dead space management to prevent local recurrence. We report outcome after antibiotic loaded biocomposite (ALB). 1. for management of infected bone defects. Method. We report a consecutive series of 97 patients with chronic OM treated at one institution by a multidisciplinary team, using a single-stage revision protocol inspired by a recently published study. 2. . The treatment protocol includes surgical debridement, tissue sampling, dead-space management using the ALB, stabilization and empirical antibiotic therapy adjusted based on culturing. Closure was performed directly, with a local flap, a free flap or secondarily. This series includes all patients operated using the ALB at our institution, since its implementation 26 months ago. The senior author (HG) performed 65 (67%) of the operations. The remaining procedures were performed by 14 different surgeons. Results. Mean age was 66.2 years (26 to 92). In 41 patients, OM followed an overlying soft-tissue infection, 30 followed surgical management of a closed fracture in the affected bone, 18 followed elective surgical procedures in the area, 5 followed open fractures of the affected bone, 2 were spontaneous following bacteremia and 1 patient had previously been diagnosed with OM in the affected bone. Seventy one (73,2%) of the included patients had systemic comorbidities (Cierny-Mader Class B hosts), thirty eight were diabetics, twenty-three were active smokers and twenty-five had a past history of smoking, fourteen consumed alcohol in quantities constituting alcohol abuse and 9 had a previous history of alcohol abuse. Patients were followed-up by chart review for a mean of 5.8 months (0 to 25). Twelve patients required a soft-tissue revision after a mean time of 2.2 months (0 to 12). Eleven patients required bone revision after a mean time of 3.4 months (0 to 10) where the ALB was re-applied in nine cases. Six patients required amputation after a mean time of 3.2 months (0 to 12). Two patients died after a 1 and 5 months respectively. Seventy patients (73%) had no adverse advents following surgery. Conclusions. An acceptable outcome was obtained considering a heterogeneous population with a high comorbidity rate and considerable smoking and alcohol abuse

Aim. Infections in long bones can be divided in osteitis, osteomyelitis and septic non-unions. All are challenging situations for the orthopaedic surgeon. Treatment is a mix with debridement, radical resection of infected tissue, void filling with different types of products, and antibiotic therapy of different kinds. In cavitary bone defects, bioglasses such as BAG-S53P4 have given good results in early or mid-term follow-up. Results of such treatment in segmental bone defects remain unknown. The goal of our study was to evaluate efficacity of active bioglass BAG-S53P4 in septic segmental bone defects. Method. A retrospective cohort study has been done in a single specific orthopaedic center devoted to treatment of infected bony situations. All cases were a severe septic bone defect. We have compared the segmental bone defects to the cavitary ones. Results were analyzed on recurrence of infection, bone healing, functional result and complication rate. Results. 14 patients were included with a minimum follow-up of 1 year after treatment. 8 were in the group “cavitary”, 6 in the group “segmental”. The mean age was 54 years-old (30–76). Sex-ratio was 2.5. All patients have been treated with bone resection and debridement of infected bone and tissue, even if more than 1 surgery was necessary in some cases. After cleaning, 7 patients have needed a local flap, and 1 a free flap. Then, all bone defects were filled up by bioglass BAG-S53P4*. Additional antibiotherapy with specific molecules based of the results of bacterial analysis, was given for a minimum time-period of 6 weeks. In the “cavitary” group, the mean volume of BAG-S53P4 was de 21.25 ml (10–60). In the “segmental” group, it was of 12.5 ml (10–20). The healing rate was of 80% in the “cavitary” group and of 100% in the “segmental” one. No complication related to the bioglass insertion was noted. Conclusions. Different publications have been made using bioglass in the treatment of infected bone with a continuous bone such as osteitis or osteomyelitis. Our study is the first one to compare specifically the results obtained in a cavitary defect where the bone is still in continuity, and in a segmental defect. Active bioglass such as the BAG-S53P4 seems to be a good option in the treatment of segmental septic bone defects in the limb. *BonAlive Biomaterials Ltd, Turku, Finland

Aim. Local concentration of antibiotic at the site of infection is a major parameter for its efficiency. However, bone diffusion is poor leading either to their non-use (ex: gentamicin) or the use of high concentration (ex: vancomycin). Local administration could optimize their local concentration combined with lower side effects. We report the clinical experience and pharmacological results of an antibiotic loaded porous alumina used to replace infected bone in 4 patients. Method. Two patients had a destroyed sternum following mediastinitis; one presented a femoral chronic osteomyelitis due to MRSA and one had an infected ankle arthroplasty. The ceramic was loaded with gentamicin in three cases and vancomycin for the ankle infection. Local dosages thanks to Redon's drain and blood samples were performed. Loading was done to protect the device while implanted in an infected area and was combined with conventional antibiotic therapy. Results. In comparison to pharmacological parameters: C. max. /MIC>8 for gentamicin or AUC/MIC>400 for vancomycin, local concentrations were dramatically higher than the one needed (table). Vancomycin concentration was still high after H48. Meanwhile, blood samples didn't find the presence of gentamicin during the 48 hours following implantation. After more than one year of follow-up for all the patients, there is no relapse of infection or signs of device infection, whereas all samples perform during implantations grew with bacteria, meaning that loaded antibiotic played a major role avoiding device colonization in combination with surgical debridement and cleaning. Conclusions. This mode of administration allows an optimization of the antibiotic delivery, maximizing local concentrations while reducing systemic toxicity. In addition, ceramic mechanical characteristics allow bone replacement (strength >3 times the one of the cancellous bone and osseointegration) and thus enables one-stage surgery instead of two-stage like for the patient with chronic osteomyelitis thanks to a good primary stability. For any figures or tables, please contact the authors directly

Aim. Antibiotic-loaded biomaterials are often used in dead space management after excision of infected bone. This study assessed the chronological progression of new bone formation in infected defects, filled only with an absorbable, osteoconductive bone void filler with Gentamicin (1). Method. 163 patients were treated for osteomyelitis or infected fractures with a single-stage excision, implantation of antibiotic carrier, stabilisation and wound closure. All had Cierny & Mader Type III (n=128) or Type IV (n=35) infection. No bone grafting was performed in any patient. Patients were followed up for a minimum of 12 months (mean 21.4 months; 12–56). Bone void filling was assessed on serial digitised, standardized radiographs taken immediately after surgery, at 6 weeks, 3, 6 and 12 months and then yearly. Data on defect size, location, degree of void filling, quality of the bone-biomaterial interface and material leakage were collected. Bone formation was calculated at final follow-up, as a percentage of initial defect volume, by determining the bone area on AP and lateral radiographs to the nearest 5%. Results. 138 patients had adequate radiographs for assessment. Infection was eradicated in 95.7%. 2.5% of patients suffered a fracture during follow-up. Overall, bone formation was good (mean 73.8% defect filling), with one quarter of patients having complete defect filling and 87% having more than 50% of the defect healed. Bone formed better in metaphyseal defects compared to diaphyseal defects (mean 79% filling vs 66%; p<0.02). Good interdigitation of the biomaterial with the host bone, seen on the initial radiograph, was associated with more bone formation (77% vs 69%; p=0.021). Leakage of the biomaterial out of the defect reduced mean bone formation from 77% to 62% (p=0.006). 38 cases had radiographs more than 2 years after implantation. In 24 (63.2%), bone formation continued to increase after the first year radiograph. Conclusion. This biomaterial was effective in allowing significant amounts of bone to form in the defect. This removed the need for bone grafting in this series, with a low risk of fracture or recurrent infection. However, bone formation is affected by the site of the lesion and the adequacy of filling at surgery. It is important to achieve good contact between the bone surface and the biomaterial at operation. Bone formation is slow and progresses for at least 2 years after implantation, in two thirds of patients

Aim. The aim of this work was to evaluate, via foot and ankle TC scans, the outcomes of the use of a bone substitute (CERAMENT|™G) and the growth of native bone in the treatment of osteomyelitis (OM) of the diabetic foot. Method. In nine patients from July 2014 to December 2016 we used a Calcium Sulphate Hemihydrate + Hydroxyapatite + Gentamicin Sulfate (CSH + HA + GS) compound to fill resected bone voids following surgical intervention in OM diabetic foot cases. Of these nine patients, three were female and six were male and their ages were between 49 and 72 years. Four patients had hindfoot involvement and underwent partial calcanectomy. Two patients presented a rocker-bottom Charcot foot pattern III according to Sanders and Frykberg's classification and were treated with esostectomy of the symptomatic bony prominence of the midfoot. One patient presented OM of the 3°, 4° and 5° metatarsal bones. One patient underwent partial resection of the midfoot and hindfoot with arthrodesis stabilised by an internal-external hybrid fixator. One patient with a Charcot foot pattern IV-V underwent partial talectomy and calcanectomy with arthrodesis stabilised by an internal-external hybrid fixator. In all these patients - after removal of the infected bone - we applied 10 to 20 ml CSH + HA + GS filling the residual spaces with the aim of stabilising the remaining bone fragments. The uniqueness of this product is that it induces native bone growth, while the synthetic bone disappears and antibiotic is released into the surrounding tissues. In March 2018, the above nine patients underwent foot and ankle TC scans to evaluate bone growth. Results. The first four patients showed new bone formation in the calcaneus. Two patients with previous midfoot destruction showed chaotic but stable bone formation. The patient with metatarsal OM showed partial bone healing with residual pseudoarthrosis. Both the two patients who underwent arthrodesis with hybrid fixators showed a plantigrade and stable foot even though a heel wound is still present in one of the patients. All patients except this one are now wearing suitable shoes as post-operative wounds have healed. The patient still with the heel wound is walking with an aircast brace. Conclusion. The TC scans have shown new bone formation sufficient to stabilise the foot and allow ambulation. In particular, very good results come from the filling of the calcaneus, probably due to the anatomy of the bone itself

Aim. Simultaneous use of Ilizarov techniques with transfer of free muscle flaps is not current standard practice. This may be due to concerns about duration of surgery, clearance of infection, potential flap failure or coordination of surgical teams. We investigated this combined technique in a consecutive series of complex tibial infections. Method. A single centre, consecutive series of 45 patients (mean age 48 years; range 19–85) were treated with a single stage operation to apply an Ilizarov frame for bone reconstruction and a free muscle flap for soft-tissue cover. All patients had a segmental bone defect in the tibia, after excision of infected bone and soft-tissue defects which could not be closed directly or with local flaps. We recorded comorbidities, Cierny-Mader and Weber-Cech classification, the Ilizarov method used, flap type, follow-up duration, time to union and complications. Results. 26 patients had osteomyelitis and 19 had infected non-union. Staphylococci were cultured in 25 cases and 17 had polymicrobial infections. Ilizarov monofocal compression was used in 14, monofocal distraction in 15, bifocal compression/distraction in 8, and bone transport in 8. 8/45 had an additional ankle fusion, 7/45 had an angular deformity corrected at the same time and 24 also had local antibiotic carriers inserted. Median time in frame was 5 months (3–14). 38 gracilis, 7 latissimus dorsi and 1 rectus abdominus flaps were used. One flap failed within 48 hours and was revised (flap failure rate 2.17%). There were no later flap complications. Flaps were not affected by distraction or bone transport. Mean follow-up was 23 months (10–89). 44/45 (97.8%) achieved bony union. Recurrence of infection occurred in 3 patients (6.7%). Secondary surgery was required to secure union with good alignment in 8 patients (17.8%; docking site surgery in 6, IM nailing in 2) and in 3 patients for infection recurrence. All were infection free at final follow-up. Conclusions. Simultaneous Ilizarov reconstruction with free muscle flap transfer is safe and effective in treating segmental infected tibial defects, and is not associated with an increased flap failure rate. It shortens overall time spent in treatment, with fewer operations per patient. However, initial theatre time is long and a committed multidisciplinary team is required to achieve good results

Surgical treatment of infected bones with vascularised bone grafts is well established as an efficient strategy since several years. Nevertheless orthopaedic and trauma surgeons seem to apply vascularised bone grafts as the last treatment option only. Two strategies exist for treatment of chronically infected bones with vascularised bone grafts. First: Complete resection of the infected, often non-united part of the bones and reconstruction with large vascularised bone grafts, mostly fibular grafts. Second: Augmentation of the kept and intact parts of the bones with vascularised bone grafts. Two small series of patients are presented to illustrate both techniques and to show the results and outcome. Resection of big parts of the tibia and reconstruction with mostly ipsilateral fibular grafts – single barrel in children and double barrel in adults – led to uneventful healing in all cases. Augmentation of radius, femur and calcaneus with vascularised grafts from the iliac crest or the scapula was followed by primary healing, too. All patients were disburdened from infection up to now and regained full extremity function. The presented vascularized bone grafts did not only salvage the extremities but also could maintain their functionality. The procedure is demanding, but reliable and safe at a low rate of complications. Thus vascularised bone grafts should not only be used as ultimative salvage procedures, but as early as possible whenever standard treatments for osteomyelitis fail

Antibiotic concentration in infected bone is a major determinant of clinical response. As glycopeptides and fluoroquinolones are widely used for the treatment of bone infections, aim of our study was to assess their diffusion in infected human bone. Patients with a posttraumatic septic pseudoarthrosis undergoing debridement of infected tissue, who received a glycopeptide or a fluoroquinolone for > 1 week, were studied. Plasma and bone specimens were collected intraoperatively for phamacokinetic and microbiologic assays at a mean of 4.1h after antibiotic administration. Bone samples were crushed and concentrations were measured by HPLC-UV method. Overall plasma exposure was also determined with daily sampling. 16 patients were studied. 6 patients received iv vancomycin 1 g bid over a 1-hr infusion Bone cultures grew E. faecalis, MRSA and MRSE (MIC < 2 mg/L). Mean plasma concentration of vancomycin at time of osteotomy was 19.8 mg/L. Mean bone concentrations were 2.4 mg/L in cortical and 7.1 mg/L in cancellous bone, with a mean bone extraction of 12 % and 36 %, respectively. 4 patients were treated with iv teicoplanin 10/mg/Kg for MRSA infection (MIC < 2 mg/L). Mean bone concentrations were 8.9 mg/L and 37 mg/l respectively for cortical and cancellous bone, respectively corresponding to 6% and 25% of plasma levels. Six patients were treated with a fluoroquinolone. 3 patients received iv ciprofloxacin 400mg bid and E. coli grew from bone samples(MIC = 0.5 mg/L). Mean Plasma concentration of ciprofloxacin at the time of osteotomy was 3.6 mcg/mL. Mean bone concentrations were 1.7 mg/L in cortical bone and 30.2 mg/L in cancellous and newly formed bone, with respective bone/ plasma ratios of 0.5 and 8.4. 3 patients were administered iv levofloxacin 500mg qd and Enterobacter spp. were isolated (MIC = 1 mg/L). Mean plasma concentration at the time of surgery was 2.5 mcg/mL. Mean bone concentrations were 0.3 and 2.69 mcg/mL in cortical and cancellous bone, respectively. To our knowledge this is the first study that compares different antibiotic’s concentration in infected bone with the same dosing procedure. Both vancomycin and teicoplanin provided mean bone concentrations exceeding the susceptibility breakpoint of the infecting agents. Higher and constant glycopeptides plasma levels may be required for preventing recurrencies in bone infections. Only ciprofloxacin provided cortical bone concentrations higher than the susceptibility breakpoint of the infecting agent, and similar to those reported in non-infected bone. Ciprofloxacin concentration in cancellous bone and in bony callus were far higher than those detected in plasma, which may be related to an augmented vascularization and/or selective accumulation of fluoroquinolones into regenerating bone, as observed in children’s cartilage growth plate. Ciprofloxacin may be therefore preferred to levofloxacin