Aim. The SOLARIO trial is a randomised controlled non-inferiority trial of antibiotic strategy for bone and joint infection. SOLARIO compares short or long post-operative systemic antibiotic duration, for patients with confirmed infections, who had local antibiotics implanted and no infected metalwork retained when undergoing surgery. This analysis compared systemic antibiotic use in the short (intervention) and long (standard of care) arms of the trial, in the 12 months after index surgery. Method. Data was collected prospectively from study randomisation, within 7 days of index surgery. All systemic antibiotics prescribed for the index infection were recorded, from health records and patient recall, at randomisation, 6 weeks, 3-6 months and 12 months after study entry. Start and end dates for each antibiotic were recorded. Results. 251 patients were randomised to short systemic antibiotics (up to 7 post-operative days) and 249 patients, to long systemic antibiotics. 5 participants in the short group and 2 participants in the long group withdrew from study follow-up. Complete data for all systemic antibiotics taken in the 12 months following surgery, were available for 237 participants in the short group and 236 participants in the long group. 80 participants across both groups were noted as having deviated from their assigned treatment strategy. Both groups received empiric antibiotics, predominantly vancomycin and meropenem, for up to 7 days after surgery. Considering each prescribed antibiotic as a separate duration (even when administered concurrently), participants assigned to standard care received a mean of 74.9 antibiotic-days. Participants assigned to short systemic antibiotics received a mean of 27.5 antibiotic-days in the 12 months after surgery. The most commonly prescribed antibiotics in both treatment groups were vancomycin and meropenem: these antibiotics accounted for 7.1 days prescribed per participant in the long group, and 6.3 days in the short group (p=0.37). Reasons for post-randomisation antibiotic prescribing in the short treatment group included later planned surgery, identification of bacteria requiring additional systemic antibiotics, and treatment of superficial wound infections. WHO AWaRe classification ‘watch’ and ‘reserve’ group antibiotics, such as ciprofloxacin, rifampicin, vancomycin and meropenem, accounted for 39.4 antibiotic-days per long group participant, and 16.5 antibiotic-days per short group participant. Conclusions. Considering the combined duration of all systemic antibiotics prescribed over 12 months, including those co-administered, participants in the short arm of the SOLARIO trial received considerably fewer days of all antibiotic classes, and particularly those antibiotics restricted in the WHO AWaRe classification (2021)

Aim. This retrospective study evaluated the outcome of treatment for unhealed fracture-related infections (FRI). Methods. We identified a consecutive, single-centre cohort of patients having treatment for an FRI Consensus confirmed FRI. All fractures were unhealed at the time of treatment. Patients were followed up for at least one year. Successful outcome was a healed fracture without recurrent infection. Lack of union, persistent infection and/or unplanned reoperation defined failure. Results. Demographics: 183 patients (184 FRIs) with mean age 52.1 years (range 17-96) were treated and followed up for a mean of 2.8 years (range 1-9.4). Mean duration of FRI was 1.1 years with 65 (35.5 %) presenting within 6 months of injury. 118 patients had established infected non-union. FRI was most frequent in the tibia (74), femur (48) and humerus (24). 171 patients were BACH Complex. 75.5% of FRIs were culture positive, with Staph. aureus being the most frequent organism. Polymicrobial infection and Gram negative cultures were common (25.5% and 33.6%). Treatment: 98.3% of surgeries were performed in one stage with just 3 planned 2-stage procedures (2 endoprosthetic replacements and 1 free fibular flap). No bone graft was used in any surgery and all wounds were closed at first operation. 48 cases (26%) required flap coverage (29 free flaps and 19 local flaps). Local antibiotics were used in 124 cases (67.4%) of primary surgeries. All patients had sampling, debridement, systemic antibiotics and wound closure. 40 (21.7%) had DAIR, 31 (16.8%) had new internal fixation and 105 (57.1%) had external fixation (including 79 Ilizarov fixators). Outcomes: After primary surgery, 84.6% of all patients were infection-free and 77.2% had united. After further surgery, 98.8% were infection-free and 98.1% had united. External fixation techniques achieved infection eradication in 89.1% compared to 71.7% with any internal fixation (p=0.005). Primary internal fixation achieved union in 81.7% compared to 74.3% with external fixation (p=0.27). Secondary surgery after external fixation was mainly docking site fixation. Conclusion. Unhealed FRIs present a difficult challenge for treatment. This large series demonstrated that single-stage treatment, without bone grafting, gave acceptable results with few reoperations. Primary external fixation gave more certainty of infection eradication but required more reoperations to secure union. However, this difference in reoperation was not statistically significant. We strongly advocate managing these patients with a multidisciplinary team which can treat all aspects of the condition

Introduction. Since the expanded war in Ukraine in 2022, explosives, mines, debris, blast waves, and other factors have predominantly caused injuries during artillery or rocket attacks. These injuries, such as those from shelling shrapnel, involve high-energy penetrating agents, resulting in extensive necrosis and notable characteristics like soft tissue defects and multiple fragmentary fractures with bone tissue defects and a high rate of infection complications caused by multi resistant gram-negative (MRGN) pathogens. Material and Methods. We conducted a prospective study at our center between March 2022 and December 2023. Out of the 56 patients from Ukraine, 21 met the inclusion criteria who had severe war injuries were included in the study. Each of these patients presented with multiple injuries to both bones and soft tissues, having initially undergone treatment in Ukraine involving multiple surgeries. The diagnosis of infection was established based on the EBJIS criteria. Prior to our treatment patients had undergone multiple revision surgeries, including debridement, biopsies, implant and fixator replacement. Additionally, soft tissue management required previously VAC therapy and flap reconstruction for successful treatment. Results. All 21 infections manifested as bone infections (11; 52%), followed by implant-associated infections (5; 24%), soft tissue infections (4; 19%), and septic arthritis (1; 5%). In all patients, the infection was polymicrobial, caused by 3- and 4-MRGN pathogens, as Klebsiella pneumonia 4MRGN, Proteus mirabilis 4MRGN, Enterobacter cloacae 4MRGN etc. Upon admission, all patients carried a diagnosis and exhibited signs indicative of chronic infection. 19 (90.5%) patients required complex antibiotic regimens combined with multiple wound revisions and debridements, changes of fixators and combination of systemic and local antibiotic therapy. In 6 patients (28%) high dosages of local antibiotics such as gentamycin, vancomycin and meropenem were incorporated into a carrier of bio-absorbable calcium sulfate, calcium sulfate/hydroxyapatite which were introduced into the hip joint, femoral canal or bone defect for dead space management during the surgery. When local antibiotics were administered at intervals, the microbiology results at implantation showed negative results. 2 (9%) patients had new infections (different site, different pathogens), 1 (4.8%) is still under the treatment. In 17 (81%) patients infection complications were treated successfully with no recurrence of infection. Conclusion. War injuries result in complex bone and soft-tissue infections caused by 3-, 4-MRGN pathogens. Addressing this challenge necessitates multidisciplinary approach with multiple, thorough surgical debridements, effective local, and systemic antimicrobial therapy. As for the outlook we can see potential in local antibiotic carriers

Aims. Bone and joint infections cause significant morbidity, often requiring combination medical and surgical treatment. The presence of foreign material reduces the number of organisms required to cause an infection. The aim of this study was to assess whether there was a difference in the species of organism identified on culture in osteomyelitis compared to prosthetic joint infection. Method. This was a retrospective observational cohort study of patients that had surgical intervention for prosthetic joint infection or osteomyelitis with positive microbial culture between 2019 and 2022. Data including patient demographics, site of injury, BACH score for osteomyelitis and JS-BACH score for prosthetic joint infection, organism classification and antibiotic resistance to vancomycin and gentamicin were extracted from the medical record. Logistic and multiple regressions were used to adjust for potential confounding variables. Results. A total of 445 patients were included in the study; 267 patients with osteomyelitis or fracture-related infection and 177 patients with prosthetic joint infection. The patients with prosthetic joint infection were older (Mean age 70 for PJI; IQR 60-77 vs 56 for OM/FRI; IQR 39-64), more likely to be female (55.6% vs 26.2%) and had a higher BMI and ASA compared to those with osteomyelitis. Symptom duration tended to be longer in osteomyelitis/FRI (p<0.001). Staphylococcus aureus was the most common pathogen isolated in both osteomyelitis (155/267 (58.1%)) and prosthetic joint infection (85/177 (48.9%), followed by other Gram negative pathogens with 77/267 (28.8%) in osteomyelitis and 48/177 (27.1%) in prosthetic joint infection. On multivariate analysis, there was no difference between the rate of Staphylococcus aureus infection between the two groups. The rate of polymicrobial infection was higher in patients with osteomyelitis (92/267 (34.5%)) compared to prosthetic joint infection (38/177 (23.7%), however after adjustment for confounders there was no difference, p = 0.842. There was no difference in the presence of gentamicin resistant organisms or vancomycin resistant Gram positive organisms in osteomyelitis compared to prosthetic joint infection. Conclusion. Causative pathogens are similar in these two common forms of bone and joint infection. There was no significant difference in the identification, presence of polymicrobial infection or gentamicin and vancomycin resistance in organisms isolated in osteomyelitis compared to prosthetic joint infection. This may have implications for empiric antibiotic choice and local antibiotic therapy in the management of bone and joint infection

Aim. Periprosthetic joint infections follow 1-3% of arthroplasty surgeries, with the biofilm nature of these infections presenting a significant treatment challenge. 1. Prevention strategies include antibiotic-loaded bone cement; however, increases in cementless procedures means there is an urgent need for alternative local antimicrobial delivery methods. 2. A novel, ultrathin, silica-based sol-gel technology is evaluated in this research as an anti-infective coating for orthopaedic prosthetic devices, providing local antibiotic release following surgery. Method. Reduction in clinically relevant microbial activity and biofilm reduction by antimicrobial sol-gel coatings, containing a selection of antibiotics, were assessed via disc diffusion and microdilution culture assays using the Calgary biofilm device. 3. Proliferation, morphology, collagen, and calcium production by primary bovine osteoblasts cultured upon antibiotic sol-gel surfaces were examined, and cytotoxicity evaluated using Alamar blue staining and lactate dehydrogenase assays. Concentrations of silica, calcium and phosphorus compounds within the cell layer cultured on sol-gel coatings and concentrations eluted into media, were quantified using ICP-OES. Furthermore, cellular phenotype was assessed using alkaline phosphatase activity with time in culture. Results. Low antibiotic concentrations within sol-gel had an inhibitory effect on clinically relevant biofilm growth, for example 0.8 mg ml. -1. tobramycin inhibited clinically isolated S. aureus (MRSA) growth with an 8-log reduction in viable colony forming units. There was no significant difference in metabolic activity between untreated and sol-gel exposed primary bovine osteoblasts in elution-based assays. Reduction (2-fold) in metabolic activity in direct contact assays after 48 hours exposure was likely to be due to increased osteoinduction, whereas no impact upon cell proliferation were observed (p=0.92 at 14 days culture). The morphology of primary osteoblasts was unaffected by culture on sol-gel coatings and collagen production was maintained. Calcium containing nodule production within bovine osteoblastic cells was increased 16-fold after 14 days culture upon sol-gel. Conclusions. The ultrathin sol-gel coating showed low cytotoxicity, strong biofilm reducing activity and antimicrobial activity, which was comparable to antibiotics alone, demonstrating that sol-gel delivery of antibiotics could provide local antimicrobial effects to inhibit PJI growth without the need for bone cement. Future work will develop and evaluate sol-gel performance in an ex vivo explant bone infection model which will reduce the need for animal experimentation

Aim. Local antibiotics, delivered to the site of infection, achieve high tissue concentrations and are used as an adjunct to systemic therapy. Local gentamicin provides levels well above the minimum inhibitory concentration and may be sufficient on its own, however, the efficacy of single or combination local antibiotics has not been studied. This retrospective study evaluated the effect of combination aminoglycoside and vancomycin local antibiotic treatment compared to aminoglycoside alone in the surgical management of bone infection. Method. We studied patients with microbiologically confirmed osteomyelitis and fracture-related infection, who had implantation of antibiotic carriers as part of their surgical management. Data including patient demographics, type of surgery, microbiological characteristics, BACH score, duration of antibiotic treatment and clinical outcomes were collected. Failure of therapy was a composite of recurrence of infection, continued or new antimicrobial therapy, or reoperation with suspected or confirmed infection at one year after index surgery. Results. There were 266 patients who met the inclusion criteria. Nine patients died before the outcome endpoint at 12 months and five patients were lost to follow up so were excluded. 252 patients were included in the final analysis and were well matched with regard to demographics, BACH score and microbiology. 113 patients had treatment with aminoglycoside alone and 139 patients had combination aminoglycoside and vancomycin. There was no difference in the failure rate between groups; 10/113 (8.8%) in the aminoglycoside alone and 12/139 (8.6%) in the combination group, p = 0.934. There was no difference for reoperation, ongoing suppressive antibiotic use, or clinical suspicion of infection. Multivariate analysis showed that there was no added benefit of combination therapy (OR 1.54: 95%CI 0.59-4.04, p=0.38). BACH score and low BMI were associated with increased risk of failure (BACH OR 3.49: 95%CI 1.13-10.76, p=0.03; Low BMI OR 0.91: 95%CI 0.84-0.99, p-0.037). The form of the carrier material (pellets or injectable paste) had no effect on failure rate (p=0.434). Aminoglycoside resistance (confirmed and presumed) occurred in 39/113 (34.5%) of the aminoglycoside only group and 36/139 (25.9%) of the combination group (p=0.137). The presence of aminoglycoside resistance had no effect on failure rate (OR 0.39: 95%CI 0.05-3.01, p=0.37). Conclusions. Clinical outcome was not improved by the addition of vancomycin to aminoglycoside alone as local therapy for the management of osteomyelitis and FRI. Laboratory measured resistance, using currently accepted breakpoints, may not be relevant in local therapy

Aims

We aimed to determine the concentrations of synovial vancomycin and meropenem in patients treated by single-stage revision combined with intra-articular infusion following periprosthetic joint infection (PJI), thereby validating this drug delivery approach.

Aims

Periprosthetic joint infection (PJI) is a challenging complication of any arthroplasty procedure. We reviewed our use of static antibiotic-loaded cement spacers (ABLCSs) for staged management of PJI where segmental bone loss, ligamentous instability, or soft-tissue defects necessitate a static construct. We reviewed factors contributing to their failure and techniques to avoid these complications when using ABLCSs in this context.

Aims

The aim of the present study was to assess the outcomes of the induced membrane technique (IMT) for the management of infected segmental bone defects, and to analyze predictive factors associated with unfavourable outcomes.

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.

Chondrosarcoma is the second most common surgically treated primary bone sarcoma. Despite a large number of scientific papers in the literature, there is still significant controversy about diagnostics, treatment of the primary tumour, subtypes, and complications. Therefore, consensus on its day-to-day treatment decisions is needed. In January 2024, the Birmingham Orthopaedic Oncology Meeting (BOOM) attempted to gain global consensus from 300 delegates from over 50 countries. The meeting focused on these critical areas and aimed to generate consensus statements based on evidence amalgamation and expert opinion from diverse geographical regions. In parallel, periprosthetic joint infection (PJI) in oncological reconstructions poses unique challenges due to factors such as adjuvant treatments, large exposures, and the complexity of surgery. The meeting debated two-stage revisions, antibiotic prophylaxis, managing acute PJI in patients undergoing chemotherapy, and defining the best strategies for wound management and allograft reconstruction. The objectives of the meeting extended beyond resolving immediate controversies. It sought to foster global collaboration among specialists attending the meeting, and to encourage future research projects to address unsolved dilemmas. By highlighting areas of disagreement and promoting collaborative research endeavours, this initiative aims to enhance treatment standards and potentially improve outcomes for patients globally. This paper sets out some of the controversies and questions that were debated in the meeting.

Cite this article: Bone Joint J 2024;106-B(5):425–429.

Introduction. Treatment of non-union in open tibial fractures Gustilo-Anderson(GA)-3A/3B fractures remains a challenging problem. Most of these can be dealt using treatment methods that requires excision of the non-union followed by bone grafting, masquelet technique, or acute shortening. Circular fixators with closed distraction or bone transport also remains a useful option. However, sometimes due to patient specific factors these cannot be used. Recently antibiotic loaded bone substitutes have been increasingly used for repairing infected non-unions. They provide local antibiotic delivery, fill dead space, and act as a bone conductive implant, which is resorted at the end of a few months. We aimed to assess the outcome of percutaneous injection of bone substitute while treating non-union of complex open tibial fractures. Materials & Methods. Three cases of clinical and radiological stiff tibial non-union requiring further intervention were identified from our major trauma open fracture database. Two GA-3B cases, treated with a circular frame developed fracture-related-infection(FRI) manifesting as local cellulitis, loosened infected wires/pins with raised blood-markers, and one case of GA-3A treated with an intramedullary nail. At the time of removal of metalwork/frame, informed consent was obtained and Cerament-G. TM. (bone-substitute with gentamicin) was percutaneously injected through a small cortical window using a bone biopsy(Jamshedi needle). All patients were allowed to weight bear as tolerated in a well-fitting air-cast boot and using crutches. They were followed up at 6 weekly intervals with clinical assessment of their symptoms and radiographs. Fracture union was assessed using serial radiographs with healing defined as filling of fracture gap, bridging callus and clinical assessment including return to full painless weight bearing. Results. Follow-up at 6 months showed all fractures had healed with no defect or gaps with evidence of new trabecular bone and significant resorption of Cerament-G. TM. at final follow-up. There was no evidence of residual infection with restoration of normal limb function. Fractures with no internal fixation showed a mild deformity that had developed during the course of the healing, presumed due to mild collapse in the absence of fixation. These were less than 10 degrees in sagittal and coronal planes and were clinically felt to be insignificant by the patients. Conclusions. Cerament-G's unique combination of high dose antibiotics and hydroxy apatite matrix provided by calcium sulphate might help provide an osteoconductive environment to allow these stiff non-unions to heal. The matrix appears to provide a scaffold-like structure that allows new bone in-growth with local release of antibiotics helping reduce deep-seated infections. The final deformation at fracture site underlines the need for fixation- and it is very unlikely that this technique will work in mobile nonunions. Whilst similar fractures may heal without the use of bone substitute injections, the speed of healing in presence of significant fracture gap suggests the use of these bone substitutes did help in our cases. Further studies with a larger cohort, including RCTs, to evaluate the effectiveness of this technique compared to other methods are needed

Aims. Continuous local antibiotic perfusion (CLAP) has recently attracted attention as a new drug delivery system for orthopaedic infections. CLAP is a direct continuous infusion of high-concentration gentamicin (1,200 μg/ml) into the bone marrow. As it is a new system, its influence on the bone marrow is unknown. This study aimed to examine the effects of high-concentration antibiotics on human bone tissue-derived cells. Methods. Cells were isolated from the bone tissue grafts collected from six patients using the Reamer-Irrigator-Aspirator system, and exposed to different gentamicin concentrations. Live cells rate, apoptosis rate, alkaline phosphatase (ALP) activity, expression of osteoblast-related genes, mineralization potential, and restoration of cell viability and ALP activity were examined by in vitro studies. Results. The live cells rate (the ratio of total number of cells in the well plate to the absorbance-measured number of live cells) was significantly decreased at ≥ 500 μg/ml of gentamicin on day 14; apoptosis rate was significantly increased at ≥ 750 μg/ml, and ALP activity was significantly decreased at ≥ 750 μg/ml. Real-time reverse transcription-polymerase chain reaction results showed no significant decrease in the ALP and activating transcription factor 4 transcript levels at ≥ 1,000 μg/ml on day 7. Mineralization potential was significantly decreased at all concentrations. Restoration of cell viability was significantly decreased at 750 and 1,000 μg/ml on day 21 and at 500 μg/ml on day 28, and ALP activity was significantly decreased at 500 μg/ml on day 28. Conclusion. Our findings suggest that the exposure concentration and duration of antibiotic administration during CLAP could affect cell functions. However, further in vivo studies are needed to determine the optimal dose in a clinical setting. Cite this article: Bone Joint Res 2024;13(3):91–100

Aims

The aim of this study was to perform the first population-based description of the epidemiological and health economic burden of fracture-related infection (FRI).

Aims. The microbiological detection of microorganisms plays a crucial role in the diagnosis as well as in the targeted systemic and local antibiotic therapy of periprosthetic infections (PJI). Despite extensive efforts to improve the sensitivity of current culture methods, the rate of culture-negative infections is approximately 10–20% of all PJI. This study investigates an preanalytical algorithm (culture collection and direct processing in the OR) to potentially increasing culture yield in patients with PJI. Methods. Patients undergoing staged revision arthroplasty for PJI in our hospital between October 2021 and 2022 were included in this prospective pilot study. Intraoperatively twenty tissue samples were collected and distributed among 4 groups. Tissue samples were prepared according to standard without medium and in thioglycolate medium at 3 different temperatures (room temperature, 4°C, 37° for 24h before transport to microbiology) directly in the OR. The removed implants were sonicated. Cultures were investigated on days 1, 3, 7, 12, 14 for possible growth. All grown organism, the number of positive samples and the time to positivity were recorded and compared. Results. 71 patients were included (age, gender). Compared to the standard procedure the thioglycolate broth at 37°C was significantly more often culture-negative (p=0.031). No significant differences in the frequency of culture-negative samples were detected in the other groups. 8.4% (6/71) patients were culture negative in the standard culture but positive in the thioglycolate samples. In contrast, 7% (5/71) were culture negative in the thioglycolate samples but had bacterial detection in the standard approach. In 4.7% (3/63) of the patients, only the sonication showed growth, whereas 25.4% (16/63) had no growth in sonication fluid but in one of the cultures. For S. caprae, there was a significantly different distribution (p=0.026) with more frequent detection in the group with thioglycolate at 37°C. The standard procedure (p=0.005) and sonication (p=0.023) showed a shorter time to positivity of the culture compared to the thioglycolate approach at 4°C. Conclusions. No general differences could be shown between the standard preparation and the thioglycolate preparation; in particular, storage at different temperatures does not seem to result in any difference. For individual cases (8% in this study), bacterial growth was detected in the thioglycolate group that would have been culture-negative otherwise. There might be organism dependent differences in growth in different media

Aim

The objective of this systematic review is to evaluate the current evidence for or against this up-and-coming treatment modality.

Aim. Local antibiotics released through a carrier is a commonly used technique to prevent infection in orthopaedic procedures. An interesting carrier in aseptic bone reconstructive surgery are bone chips impregnated with AB solution. Systemically administered Cefazolin (CFZ) is used for surgical site infection prophylaxis however in vitro study showed that fresh frozen and processed bone chips impregnated with CFZ solution completely release the CFZ within a few hours. On the other hand irradiated freeze-dried bone chips, treated with supercritical CO2 (scCO2) have been shown to be an efficient carrier for the antibiotics vancomycine or tobramycine. With this pilot study we wanted to investigate if CFZ solution impregnation of bone chips treated with scCO2 shows a more favorable release pattern of CFZ. Method. The bone chips were prepared using the standard scCO2 protocol and were impregnated with 100 mg/ml cefazolin at different timepoints during the process: before freeze drying (BC type A), after freeze drying (BC type B) and after gamma-irradiation. 0.5g of the impregnated bone grafts were incubated with 5ml of fetal calf serum (FCS) at 37°C. At 2, 4, 6, 8 and 24h of incubation 200µl of eluate was taken for analysis. After 24h the remaining FCS was removed, bone grafts were washed and new FCS (5ml) was added. Consecutive eluate samples were taken at 48, 72 and 96h of incubation. The concentration of CFZ in the eluates was measured with the validated UPLC-DAD method. Analysis was performed in triplicate. Results. The mean concentration of CFZ in the eluate obtained from BC type A incubated for 2h was higher compared to BC type B, respectively 581 mg/l and 297 mg/l. However, the elution profile is the same for both types: the CFZ concentration in the eluates drops within the first 24h from 581 mg/l to 365 mg/l (37%) for BC type A and from 297 mg/l to 132 mg/l (56%) for BC type B. After 24h no further significant CFZ release is seen. Impregnation of the bone chips before or after gamma irradiation did not affect this elution profile. Conclusions. Bone chips treated with scCO2 show a comparable elution pattern compared to non-scCO2 treated bone chips. AB release depends on the properties of the AB, making it impossible to copy the same impregnation protocol for different antibiotics. The stability of CFZ in solution at 37°C and its release are a major concern when establishing an impregnation protocol with CFZ

Aim. To describe a 2-stage treatment pathway for managing neuropathic forefoot ulcers and the safety and efficacy of percutaneous tendo-Achilles lengthening (TAL) in out-patient clinics. Methods. Forefoot ulcers in patients with diabetic neuropathy are a result of factors that result in increased forefoot plantar pressure. Plantar flexed metatarsal heads secondary to progressive claw toe deformity and hindfoot equinus from changes within the gastrocnemius-soleus-tendo-Achilles complex, with additional contraction of tibialis posterior and peroneal longus, secondary to motor neuropathy results in progressive increase in forefoot plantar pressures. Consecutive patients, who presented to our Diabetic Foot clinic since February 2019 with forefoot ulcers or recurrent forefoot callosity were treated with TAL in the first instance, and in patients with recurrent or non-healing ulcers, by proximal dorsal closing wedge osteotomy; a 2-stage treatment pathway. Patients were followed up at 3, 6, and 12 months to assess ulcer healing and recurrence. Results. One hundred and twelve patients (146 feet) underwent TAL by 3 consultants in the out-patient clinics. Of these, 96 feet were followed for a minimum of 12 months (range 12–36 months). None had infection or wound related problems at the tenotomy sites; complete transection of the tendon was noted in 4 patients (4%) and one-patient developed heel callosity suggestive of over-lengthening. In 92 feet (96%), the ulcers healed within 10 weeks (± 4 weeks). Additional z-lengthening of peroneal longus and tibialis posterior tendons helped in patients with big-toe and 5. th. metatarsal head ulcers. In 12 feet (10%), the ulcer failed to heal or recurred, the MRI scan in these patients showed plantar flexed metatarsals secondary to progressive claw toe deformity. The ulcer in this group healed after surgical offloading with proximal dorsal closing wedge osteotomy. In patients with osteomyelitis, the intramedullary canal was curetted and filled with local antibiotic eluting agents such as Cerament G. ®. The osteotomy site was stabilised with a percutaneous 1.6mm k-wire. Conclusion. The described 2-stage treatment pathway results in long-term healing of neuropathic forefoot ulcers, and in 96% of patients, the ulcer healed after out-patient percutaneous TAL alone. TAL is a safe and effective initial out-patient procedure with improved patient outcomes

Aim. The use of bone substitutes such as calcium sulfate (CaSO4) and hydroxyapatite with local antibiotics are crucial in the treatment of osteomyelitis. They allow the treatment of the dead space and locally provide large concentrations of antibiotics. However, it is unknown whether use of local vancomycin may elute and influence on vancomycin plasma levels. The aim of this study is to assess whether the addition of vancomycin to CaSO4 with hydroxyapatite may increase vancomycin plasma concentrations in in patients with osteomyelitis and therefore alter dosage adjustments. Method. The present study investigates the vancomycin plasma concentrations at 72–94 h post-surgery after the application of local vancomycin within CaSO4 (660mg vancomycin/10cc) and hydroxyapatite bone substitute in patients treated with empiric intravenous vancomycin and surgically treated for osteomyelitis. Vancomycin plasma concentrations were analyzed in twelve patients with osteomyelitis surgically treated with local release of vancomycin by CaSO4 and hydroxyapatite and undergoing therapeutic drug monitoring (TDM) of their vancomycin plasma concentrations as it is routinely done in our hospital. From 2019 to 2022, demographic data, microbiology, type of osteomyelitis, amount of local vancomycin applied, alteration of renal function, and vancomycin levels were retrospectively analyzed. Results. Twelve patients were included: 9(75%) were men. Median (range) demographic and clinical data: age: 51(26–67) years; body mass index: 27.7(18–46.4) kg/m2;baseline serum creatinine: 0.85 (0.7–1.24)mg/dl and 5(41.7%) with and glomerular filtration rate < 90ml/min(CPD-EPI, ml/min). Most frequently isolated microorganisms were Staphylococci (58%). Seven (54%) patients were classified as Cierny-Mader Osteomyelitis type III, 3(23%) as type IV and 2(23%) as type I. Treatment data: initial dose of vancomycin: 1g/8h in 9(75.0%) and 1g/12h in 3(25%) patients, total daily dose/body weight: 35.3(15.9–46.2) mg/kg. Pharmacokinetic data:days of iv vancomycin treatment until first TDM measurement: 3(3–4) days; minimum and maximum vancomycin plasma concentrations: 9.4(3–17.3) mg/L and 19.6(11.3–33.4) mg/L, respectively; patients with therapeutic concentrations: 6(50%); infratherapeutic: 4(33.3%) and supratherapeutic/potentially toxic: 2(16.7%). These 2 patients were young, had a baseline conserved renal function and were receiving the higher dose of 1g/8h. Conclusions. Vancomycin incorporated into the bone substitute appears not to increase blood concentrations of the glycopeptide in patients with osteomyelitis treated surgically and with intravenous vancomycin. However, 2 of the 12 patients presented supratherapeutic and potentially nephrotoxic vancomycin concentrations in the first TDM measurement, even though they were young and without renal impairment and needed and unexpected dose reduction. These results suggest the need to confirm the safety of local vancomycin in further larger clinical studies