Objective

A clinical investigation into a new bone void filler is giving first data on systemic and local exposure to the anti-infective substance after implantation.

We report our experience using a biodegradable calcium sulphate antibiotic carrier containing tobramycin in the surgical management of patients with chronic osteomyelitis. The patients were reviewed to determine the rate of recurrent infection, the filling of bony defects, and any problems with wound healing. A total of 193 patients (195 cases) with a mean age of 46.1 years (16.1 to 82.0) underwent surgery. According to the Cierny–Mader classification of osteomyelitis there were 12 type I, 1 type II, 144 type III and 38 type IV cases. The mean follow-up was 3.7 years (1.3 to 7.1) with recurrent infection occurring in 18 cases (9.2%) at a mean of 10.3 months post-operatively (1 to 25.0). After further treatment the infection resolved in 191 cases (97.9%). Prolonged wound ooze (longer than two weeks post-operatively) occurred in 30 cases (15.4%) in which there were no recurrent infection. Radiographic assessment at final follow-up showed no filling of the defect with bone in 67 (36.6%), partial filling in 108 (59.0%) and complete filling in eight (4.4%). A fracture occurred in nine (4.6%) of the treated osteomyelitic segments at a mean of 1.9 years (0.4 to 4.9) after operation.

We conclude that Osteoset T is helpful in the management of patients with chronic osteomyelitis, but the filling of the defect in bone is variable. Prolonged wound ooze is usually self-limiting and not associated with recurrent infection.

Cite this article: Bone Joint J 2014; 96-B:829–36

Aim. Osteomyelitis is a difficult-to-treat disease with high chronification rates. The surgical amputation of the afflicted limb sometimes remains as the patients’ last resort. Several studies suggest an increase in mitochondrial fission as a possible contributor to the accumulation of intracellular reactive oxygen species and thereby to cell death of infectious bone cells. The aim of this study is to analyze the ultrastructural impact of bacterial infection and its accompanying microenvironmental tissue hypoxia on osteocytic and osteoblastic mitochondria. Method. 19 Human bone tissue samples from patients with osteomyelitis were visualized via light microscopy and transmission electron microscopy. Osteoblasts, osteocytes and their respective mitochondria were histomorphometrically analyzed. The results were compared to the control group of 5 non-infectious human bone tissue samples. Results. The results depicted swollen hydropic mitochondria including depleted cristae and a decrease in matrix density in the infectious samples as a common finding in both cell types. Furthermore, perinuclear clustering of mitochondria could also be observed regularly. Additionally, increases in relative mitochondrial area and number could be found as a sign for increased mitochondrial fission. Conclusions. The results show that mitochondrial morphology is altered during osteomyelitis in a comparable way to mitochondria from hypoxic tissues. This suggests that manipulation of mitochondrial dynamics in a way of inhibiting mitochondrial fission may improve bone cell survival and exploit bone cells regenerative potential to aid in the treatment of osteomyelitis

Aim. This study assessed quality of life (QoL) in patients having external fixation for treatment of osteomyelitis and fracture-related infection (OM/FRI). Method. Patients who had surgery for OM/FRI and who completed the EuroQoL EQ-5D-5L or EQ-5D- 3L questionnaires, were identified between 2010 and 2020. Patients were followed-up for 2 years after surgery. QoL was compared between patients who had either an Ilizarov frame or a monolateral external fixator with those who did not receive external fixation. Results. 165 patients were included. Of these, 37 (22.4%) underwent application of external fixation which included 23 circular frames and 14 monolateral external fixators. Patients in the frame group had more BACH ‘Complex’ infections (34/37; 91.9%), compared to non-frame patients (57/81; 70.3%). Pre-operatively, the mean EQ-index score for patients planned to receive a frame (0.278 SD 0.427) was worse compared to other treatments (0.453 SD 0.338, p=0.083). At 6 weeks after surgery, the EQ-index score remained significantly lower in frame patients compared to non-frame patients (frame: 0.379 SD 0.363; no frame: 0.608 SD 0.326, p=0.016). By 6 months, 26/37 patients had undergone frame removal. The patients who had frames in situ at 6 months had lower EQ-index scores when compared to patients who had their frames removed (frame in situ: 0.187 SD 0.213; frame removed 0.674 SD 0.206, p=0.076). At one year, 36/37 (97.3%) patients had their frame removed. QoL had greatly improved, to levels similar to non-frame patients (no frame: 0.652 SD 0.357; frame removed: 0.657 SD 0.247, p=0.949). Conclusions. Frame treatment leads to significant improvement in Quality of Life in patients suffering from osteomyelitis, with similar results in EQ5D scores after 1 year compared to patients who did not need an external fixator. These effects cannot be felt until after the frame has been removed with impaired QoL during frame treatment, especially in those patients with frames in situ for more than 6 months. This underlines the need for close and professional patient support during frame treatment for bone infection

Aim. Patient quality of life (QoL) in untreated bone infection was compared to other chronic conditions and stratified by disease severity. Method. Patients referred for treatment of osteomyelitis (including fracture related infection) were identified prospectively between 2019 and 2023. Patients with confirmed infection completed the EuroQol EQ-5D-5L questionnaire. Clinicians blinded to EQ-index score, grouped patients according to JS-BACH Classification into ‘Uncomplicated’, ‘Complex’ or ‘Limited treatment options’. A systematic review of the literature was performed of other conditions that have been stratified using EQ-index score. Results. 257 patients were referred, and 219 had suspected osteomyelitis. 196 patients had long bone infection and reported an average EQ-index score of 0.455 (SD 0.343). 23 patients with pelvic osteomyelitis had an average EQ-index score of 0.098 (SD 0.308). Compared to other chronic conditions, patients with long-bone osteomyelitis had worse QoL when compared to different types of malignancy (including bladder, oropharyngeal, colorectal, thyroid and myeloma), cardiorespiratory disease (including asthma, COPD and ischaemic heart disease), psychiatric conditions (including depression, pain and anxiety), endocrine disorders (including diabetes mellitus), neurological conditions (including Parkinson's disease, chronic pain and radiculopathy) and musculoskeletal conditions (including osteogenesis imperfecta, fibrous dysplasia and x-linked hypophosphataemic rickets). QoL in long-bone infection was similar to conditions such as Prada-Willi syndrome, Crohn's disease and juvenile idiopathic arthritis. Patients who had a history of stroke or multiple sclerosis reported worse QoL scores compared to long-bone infection. Patients who had pelvic osteomyelitis gave significantly lower QoL scores when compared to all other conditions that were available for comparison in the literature. In long bone infection, 41 cases (21.0%) were classified as ‘Uncomplicated’, 136 (69.4%) as ‘Complex’ and 19 (9.7%) as ‘Limited treatment options available’. Within classification stratification, patients with ‘Uncomplicated’ long bone infections reported a mean EQ-index score of 0.618 (SD 0.227) which was significantly higher compared to ‘Complex’ (EQ-index: 0.410 SD 0.359, p=0.004) and ‘Limited treatment options available’ (EQ-index: 0.400 SD 0.346, p=0.007). Conclusions. Bone and joint infections have a significant impact on patient quality of life. It is much worse when compared to other common chronic conditions, including malignancy, cardiovascular and neurological diseases. This has not been previously reported but may focus attention on the need for more investment in this patient group

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

Aim. To compare pre-referral microbiology and previous bone excision in long bone osteomyelitis with intra-operative microbiology from a specialist centre. Method. A prospective observational cohort study of patients referred to a single tertiary centre who met the following criteria: (i) aged ≥18 years, (ii) received surgery for long bone osteomyelitis and (iii) met diagnostic criteria for long bone osteomyelitis. Patient demographics, referral microbiology and previous surgical history were collected at the time of initial clinic appointment. During surgery, a minimum of 5 intra-operative deep tissue samples were sent for microbiology. Antimicrobial options were classified from the results of susceptibility testing using the BACH classification of long bone osteomyelitis as either Ax (unknown or culture negative), A1 (good options available) or A2 (limited options available). The cultures and susceptibility of pre-referral microbiology were compared to the new intra-operative sampling results. In addition, an association between previous osteomyelitis excision and antimicrobial options were investigated. Results. 79 patients met inclusion criteria during the study period. From these, 39 (49.4%) patients had information available at referral regarding microbiology obtained from either sinus swab (n=16), bone biopsy (n=11), previous osteomyelitis excision sampling (n=7), aspiration (n=4) or blood culture (n=1). From these 39 patients, microbiology information at referral fully matched microbiology samples taken at operation in 8 cases (20.5%). Fifteen of the 39 patients (38.5%) had a different species isolated at surgery compared to referral microbiology. The remaining 16 patients (41.0%) had a culture-negative osteomyelitis on surgical sampling. Based on the microbiology obtained in our centre, 35 patients were classified as A1 (44.3%), 15 as A2 (18.9%) and 29 as culture negative, Ax (36.7%). Patients who had received previous excision of osteomyelitis before referral (n=32, 40.5%) had an increased odds ratio (OR) of having microbiology with limited antimicrobial options compared to those undergoing primary osteomyelitis excision (OR: 3.8, 95% CI 1.2 – 11.2, P=0.023, Fisher's exact test). Conclusions. Patients are frequently referred with limited microbiological information. Pre-referral microbiology in long bone osteomyelitis correlated with intra-operative samples taken at our centre in less than one quarter of cases. Pre-referral microbiology data should be used with caution for planning treatment in osteomyelitis. Previous surgery for osteomyelitis was associated with microbiology culture with limited antimicrobial treatment options

Fracture related infection, in particular chronic osteomyelitis, requires complex management plans. Meta analyses and systematic reviews have not found a gold standard of treatment for this disease. In 2017 an alternative treatment protocol was undertaken in our institution; whereby staged surgery with the use of cheaply manufactured tailored antibiotic cement rods was used in the treatment of chronic osteomyelitis, secondary to traumatic long bone fractures. Short term outcomes for this protocol demonstrated a 75.7% microbiological resolution to a negative culture and a good clinical outcome of 84.2% overall was demonstrated in terms of sinus resolution, skin changes, pain and function. Our aim now was to assess the long term outcomes of this treatment strategy. A cross-sectional study of patients who had previously undergone the set treatment protocol was performed. Patient satisfaction, effects on activities of daily living, return to work and clinical improvement at 5 years following the intervention were assessed using a patient questionnaire and the validated AAOS lower limb score. The average AAOS lower limb score was 88 which was en par to other similar studies. 80% of patients had returned to some form of work. Ongoing mild pain was a persistent problem for 50% of the patients however 98% of the patients were overall satisfied with the treatment satisfaction at 5 years. Only 1 patient required further treatment. 8 patients could not be located for follow up. Chronic osteomyelitis remains a complex disease to treat. This treatment protocol demonstrates favourable microbiological, serological and clinical short term outcomes and favourable patient satisfaction and functional long term outcomes at 5 years. Our study highlights antibiotic targeted cement rods as a feasible treatment option in managing chronic osteomyelitis

Aim. Calcaneal osteomyelitis remains a difficult condition to treat with high rates of recurrence and below knee amputation; particularly in cases of severe soft tissue destruction. This study assesses the outcomes of combined ortho-plastics treatment of complex calcaneal osteomyelitis. Method. A retrospective review was performed of all patients who underwent combined single stage ortho-plastics treatment of calcaneal osteomyelitis (2008- 2022). Primary outcome measures were osteomyelitis recurrence and BKA. Secondary outcome measures included flap failure, operative time, complications, length of stay. Results. 33 patients (16 female, 17 male, mean age = 54.4 years) underwent combined ortho-plastics surgical treatment for BACH “complex” calcaneal osteomyelitis with a median follow-up of 31 months (s.d. 24.3). 20 received a local flap, 13 received a free flap. Fracture-related infection (39%) and diabetic ulceration (33%) were the commonest causes. 54% of patients had already undergone at least one operation elsewhere. There were seven cases of recurrent osteomyelitis (21%); all in the local flap group. One patient required a BKA (3%). Recurrence was associated with increased mortality risk (OR 18.8 (95% CI 1.5–227.8), p=0.004) and reduced likelihood of walking independently (OR 0.14 (95% CI 0.02–0.86), p=0.042). Local flap reconstruction (OR 15 (95% CI 0.8–289.6), p=0.027) and peripheral vascular disease (OR 39.7 (95% CI 1.7–905.6), p=0.006) were associated with increased recurrence risk. Free flap reconstruction took significantly longer intra-operatively than local flaps (443 vs 174 minutes, p<0.001), but without significant differences in length of stay or frequency of out-patient appointments. Conclusions. Single stage ortho-plastic management was associated with 79% eradication of infection and 3% amputation in this complex and co-morbid patient group. Risk factors for failure were peripheral vascular disease and local flap reconstruction. Whilst good outcomes can be achieved, this treatment requires high levels of in-patient and out-patient care

Aim. To report outcomes of soft tissue reconstruction using free tissue transfer for the treatment of tibial osteomyelitis as part of a single-stage, ortho-plastic procedure. Method. Patients who underwent ortho-plastic reconstructive surgery to excise tibial osteomyelitis in combination with free tissue transfer in one stage were included. Patients underwent surgery between 2015 and 2024 in a single specialist centre within the UK. Baseline patient information, demographics, and infection information was recorded. Adverse outcomes were defined as (i) flap salvage required, (ii) flap failure and (iii) recurrence of infection. Patient reported quality of life was measured using the EuroQol EQ-5D-5L index score. Pre-operative QoL was compared to QoL at 1 year with a control group of 53 similar patients who underwent surgical treatment for tibial osteomyelitis without a free flap (local flap or primary closure). Results. Ninety-three patients were eligible for inclusion, with a mean age of 52 years (range 18–90). 77/93 (82.8%) had a free muscle flap with the remainder (17.2%) receiving a fasciocutaneous flap. The donor tissue was defined as 57 gracilis, 6 latissimus dorsi, 14 hemi-latissimus dorsi, and 16 anterolateral thigh. The recipient area of the tibia was distal 1/3 in 52 cases, middle 1/3 in 27 cases and proximal 1/3 in 12 cases. The average flap ischaemic time was 70 minutes (range 28 to 125). Seven patients (7.5%) required urgent flap salvage at a median time of 1.0 day (range 0.5 – 4.0). Of these, 4 (4.3%) went on to have total flap failure, of which 2 patients underwent below knee amputation subsequently. Flap failure was due to either arterial (n=2) or venous (n=2) anastomotic thrombus. There were 3 (3.2%) episodes of confirmed infection recurrence within the first year after the index procedure. EQ-index scores at 1-year post-operatively were significantly improved when compared to pre-operative scores (p=0.008). At 1-year post-operatively, EQ-index scores in patients who underwent free flap was similar compared to local flaps (p=0.410) and in those who underwent primary closure for tibial osteomyelitis (p=0.070). Conclusions. Microsurgical single stage surgery can achieve high flap survival rate (95.7%). Free flaps fail early due to anastomotic thrombus with no late failures seen. Free tissue transfer does not appear to give inferior QoL compared to matched patients with local flaps or direct closure in tibial osteomyelitis

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

To compare the costs of treatment and income received for treating patients with tibial osteomyelitis, comparing limb salvage with amputation. We derived direct hospital costs of care for ten consecutive patients treated with limb salvage procedures and five consecutive patients who underwent amputation, for tibial osteomyelitis. We recorded all factors which affect the cost of treatment. Financial data from the Patient-Level Information and Costing System (PLICS) allowed calculation of hospital costs and income received from payment under the UK National Tariff. Hospital payment is based on primary diagnosis, operation code, length of stay, patient co-morbidities and supplements for custom implants or external fixators. Our primary outcome measure was net income/loss for each in-patient episode. The mean age of patients undergoing limb salvage was 55 years (range 34–83 years) whereas for amputation this was 61 years (range 51–83 years). Both groups were similar in Cierny and Mader Staging, requirement for soft-tissue reconstruction, anaesthetic technique, diagnostics, drug administration and antibiotic therapy. In the limb salvage group, there were two infected non-unions requiring Ilizarov method and five free flaps. Mean hospital stay was 15 days (10–27). Mean direct cost of care was €16,718 and mean income was €9,105, resulting in an average net loss of €7,613 per patient. Patients undergoing segmental resection with Ilizarov bifocal reconstruction and those with the longest length of stay generated the greatest net loss. In the amputation group, there were 3 above knee and 2 below knee amputations for failed previous treatment of osteomyelitis or infected non-union. Mean hospital stay was 13 days (8–17). Mean direct cost of care was €18,441 and mean income was €15,707, resulting in an average net loss of €2,734 per patient. Length of stay was directly proportional to net loss. The UK National Tariff structure does not provide sufficient funding for treatment of osteomyelitis of the tibia by either reconstruction or amputation. Average income for a patient admitted for limb salvage is €6,602 less than that for amputation even though the surgery is frequently more technically demanding (often requiring complex bone reconstruction and free tissue transfer) and the length of hospital stay is longer. Although both are significantly loss-making, the net loss for limb salvage is more than double that for amputation. This makes treatment of tibial osteomyelitis in the UK National Health Service unsustainable in the long term

Chronic osteomyelitis is a challenging clinical problem. Aggressive debridement, bony fixation, obliteration of dead space and vascularised soft tissue coverage with appropriate antimicrobial therapy are essential to successful management of this condition. The gracilis muscle flap is the workhorse flap in our unit for reconstruction of limb osteomyelitis. We describe the experience and use of this flap in our unit over a 3 year period. Clinical records were reviewed from a prospectively-maintained Oxford Free Flap Database and patient notes. All patients who received a free gracilis flap reconstruction as part of the treatment of osteomyelitis between 2011 and 2014 were included in the study. 40 patients received free gracilis flaps; 38/40 for lower limb and 2/40 for upper limb osteomyelitis. Two were myocutaneous flaps, and the remainder were muscle only. The return to theatre rate was 12.5% with a total flap loss rate of 5%. Other flap-specific complications include partial flap loss (2.5%), flap site haematoma (2.5%), donor site haematoma (2.5%) and seroma (2.5%). General complications included pulmonary embolism (2.5%) and death from sepsis (2.5%). All but 2 patients were treated successfully and remain disease free following their initial surgery, with a mean follow up of 12.4 months (range 1–23 months). We have found that the free gracilis muscle flap is effective in the successful treatment of osteomyelitis, with a low complication rate

Treatment of osteomyelitis is a challenge for every surgeon, but even more so in low and middle income countries, because of delay in presentation, lack of resources and troublesome follow-up. We present a series of fifteen patients, treated for osteomyelitis in 2014 in a rural Ghanean hospital with one-year follow up. All bony defects were filled using Bonalive®. Fifteen consecutive patients with osteomyelitis were included in this study and treated with Bonalive® in March 2014. The group consisted of twelve men and three women (age 10–46y, mean 26y). All patients consented and the study was approved by the hospital's ethical committee. Imaging was performed preoperatively, immediate postoperatively and at various occasions thereafter with final X-rays taken at follow-up in April 2015. All were treated by extensive debridement of the osteomyelitic bone, sequestrectomy, saucerisation and filling of the defect with Bonalive® granules (1,0–2,0 mm in size). Primary closure of the wound was possible in all cases. Fistulae were curetted, not closed. Peroperatively, multiple culture specimens were taken and all patients received a course of intravenous antibiotics for a week, continued orally thereafter for another week. Patients were regularly followed up postoperatively and final review took place in April 2015. Of all fifteen treated patients, only seven were seen back in April 2015, more than one year postoperatively. The osteomyelitis was located in the femur in seven patients, tibia in seven and the humerus in two. Microbiology showed growth of St. aureus in six patients, Proteus species in six, St. epidermidis in two and pseudomonas in one. Of the seven patients presenting at one year follow-up, all had relief of symptoms for at least three months. Two were completely symptom free, the other five still had one or more draining fistulae. Initial X-rays showed good filling of all osteomyelitic defects with the bioglas granules. Treatment of osteomyelitis remains a challenge in low and middle income countries. First, there is almost always a delay in presentation and most cases have become chronic by the time they are treated. Secondly, some sequesters were missed and therefore not removed at surgery, due to the lack of good initial x-ray films. Thirdly, there is often no access to microbiological diagnostics. At last, a lot of patients are lost to follow-up. In our opinion, the Bonalive® product delivered it's claims, but the overall circumstances in which we treated these patients were importantly responsible for the overall suboptimal outcome

Aim. To compare outcomes and incidence of adverse events (AE) of colistin versus tigecycline for treatment of patients with carbapenem-resistant Acinetobacter baumannii (CRAB) osteomyelitis. Method. Retrospective study. Records of 111 patients with microbiologically confirmed CRAB osteomyelitis were analyzed. Colistin (34 cases) and tigecycline (31 cases) were the main drugs used for treatment of extremely-drug resistant (XDR) isolates. Patients who received these two antimicrobials were compared according to baseline features (sex, age, length of hospital stay, Charlson index, presence of comorbidities or immunosuppression, previous renal disease, smoking, alcoholism or use of illicit drugs, previous orthopedic surgery on affected limb, topography of infection, classification of osteomyelitis, ASA score, infection related to pressure ulcer or neuropathic foot, presence of implant, need for soft tissue repair or negative pressure therapy and previous antimicrobial use), clinical outcome after 12 months of treatment (remission of infection was considered the favorable outcome; recurrence of infection, amputation and death were considered unfavorable outcomes; loss of follow-up was analyzed separately) and AE during treatment (impaired renal function; liver abnormalities; nausea; skin rash; neurological abnormalities and other events in general). Quantitative variables were described using summary measures and compared using Student's t or Mann-Whitney tests. Qualitative characteristics were described with absolute and relative frequencies and compared using chi-square or exact tests (Fisher's exact or likelihood ratio test). Results. Regarding baseline characteristics, proportion of male patients was higher in the group treated with colistin (p = 0.028). In the group treated with tigecycline, there was a significant predominance of smokers (p = 0.021) and patients with chronic osteomyelitis (p = 0.036). Regarding clinical outcomes after 12 months of treatment, there was no difference between groups. Overall incidence of AE was significantly higher among patients treated with colistin (p=0,047), as well as renal impairment (p = 0.003). Incidence of nausea was higher in patients treated with tigecycline (p = 0.046), but there was no difference between groups in relation to altered liver enzymes and other events. Conclusions. In this retrospective analysis, there was no significant difference between clinical outcomes of patients with CRAB osteomyelitis treated with colistin compared to tigecycline. Although the occurrence of nausea was greater in the group receiving tigecycline, this antimicrobial appeared to have a better safety profile for treatment of osteomyelitis related to XDR A. baumannii

Aim. Chronic osteomyelitis reflects a progressive inflammatory process of destruction and necrosis affecting bone architecture. It presents a challenge to manage, requiring multi-stage multidisciplinary interventions, and the literature reports a wide variety of treatment strategies. This systematic scoping review aims to map and summarise existing literature on treatment of chronic osteomyelitis of the femur and tibia and investigates the full range of treatments reported in order to enhance the reader's understanding of how to manage this complex condition. Method. A comprehensive computer-based search was conducted in PubMed, EMBASE, MEDLINE, Emcare and CINAHL for articles reporting treatment of chronic tibial/femoral osteomyelitis. Two reviewers independently performed a two-stage title/abstract and full-text screening, followed by data collection. Studies were included if they described any treatment strategy including at least one surgical intervention. Key information extracted included causative pathogens, treatment protocol and outcome i.e. both success rate, defined as remission achieved following initial treatment with no recurrence during followup, and recurrence rate. Results. A total of 1230 articles were identified, and 40 articles (2529 patients) ultimately included. Although a wide variety of treatment protocols are reported, all revolve around three key principles: removal of infected tissue, dead space management and antibiotic therapy. Variations are evident when considering use of extensive versus more conservative debridement techniques, and delivery and regime of antibiotic therapy, e.g. whether to use one of, or both systemic and local delivery. The majority (84.5%) of patients presented with stage III or IV disease according to the Cierny-Mader classification and staphylococcus aureus was the most commonly isolated organism. Although there is heterogeneity across studies in reporting outcomes, with only 29 studies reporting success rate as defined in this review, 25 (86.2%) of these reported a success rate of at least 80%. Conclusions. It is difficult to identify the optimal treatment strategy when reporting of outcomes is not standardised across studies, even in the context of similar techniques being used. Success rates across studies may also vary depending on patient demographics, comorbidities, severity, type and number of causative pathogens and follow-up length. It is now essential to identify specific patient and treatment related factors that may affect clinical outcomes. Given the current dominance of case series in the literature, there is a need for randomised controlled trials to yield further information that could aid future efficient management

Aim. Despite advances in surgical and antibiotic therapies the treatment of chronic osteomyelitis remains complex and is often associated with a significant financial burden to the National Health Service. The aim of this review was to identify the different types of single-stage procedures being performed for this condition as well as to evaluate their effectiveness. Method. Ovid Medline and Embase databases were searched for articles on the treatment of chronic osteomyelitis over the last 20 years. 3511 journal abstracts were screened by 3 independent reviewers. Following the exclusion of paediatric subjects, animal models, non-bacterial osteomyelitis and patients undergoing multiple surgical procedures we identified 13 studies reported in English with a minimum follow up of 12 months. Following a quality assessment of each study, data extraction was performed and the results analysed. Results. 505 patients with chronic osteomyelitis underwent attempted single-stage procedures. Following debridement a range of techniques are described to eliminate the remaining dead space. These include musculocutaneous flaps, insertion of S53P4 glass beads or packing with antibiotic loaded ceramic or calcium-sulphate pellets. The average follow-up ranged from 12 to 110 months. The most common organism isolated was Staphylococcus Aureus. Success was defined as resolution of pain with no recurrence of sinuses and no need for a second procedure to treat infection. Success rates ranged from 60%-100%. Conclusions. There are currently a wide range of single-stage procedures being performed for chronic osteomyelitis with varying success rates. Treating patients with these methods in specialist centres can result in resolution of infection and may lead to improved quality of life for the patient and a financial saving for the National Health Service. So far no one technique has been shown to be superior and further long term follow up data is required

Chronic osteomyelitis is a challenging problem and a growing burden for the National Health Service. Conventional method of treatment is 2 stage surgery, with debridement and prolonged courses of antibiotics. Recently single stage treatment of chronic osteomyelitis is gaining popularity due decreased patient morbidity and cost effectiveness. Dead space management in single stage treatment is accomplished by either a muscle / myocutaneous or antibiotic loaded calcium sulphate beads. We analysed the cost effectiveness of two dead space management strategies in single stage treatment of osteomyelitis. Study is designed to analyse the health economics at 2 time points; 45 days post surgery and 2 years post surgery. We report preliminary results at 45 days post surgery. Setting – Level 1 trauma centre and university hospital. Approval – Ethics committee approved study. 10 patients in each group were retrospectively analysed through patient records. Each group was identified for standard demographics, duration of procedure, hospital stay, type and duration of postoperative antibiotics, number of out patient visits in first 45 days and recurrence of infection. Table attached details the results of both groups. In health technology assessment four quadrant model, CSB appears in quadrant II suggesting that it is more cost effective. Based on small data set and on assessment only evaluating cost, at 45 days assessment, antibiotic calcium sulphate beads from a Health Economic Cost Effectiveness Analysis offers a better economic outcome. This is holding constant the morbidity of the patients and effectiveness, assuming both treatments are standards of care, which is best evaluated at 24 months. Acknowledgements. Biocomposites for funding the cost of health economist

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. For which patients is bone defect reconstruction with the Masquelet-technique after the treatment of osteomyelitis suitable and which results did we have. Methods. From 11/2011 to 4/2018 we treated 112 Patients (36f, 76m) with bone defects up 150mm after septic complications with the Masquelet-technique. We had infected-non-unions of upper and lower extremity, chronic osteomyelitis, infected knee-arthrodesis and knee- and ankle-joint-empyema. On average the patients were 52 (10–82) years old. The mean bone defect size was 48 mm (15–150). Most of our patients came from other hospitals, where they had up to 20 (mean 5.1) operations caused by the infection. Time before transfer in our hospital was on average 7,1 months (0,5–48). 77 patients received free (25) or local (52) flaps because of soft tissue-defects. 58 patients suffered a polytrauma. In 23 cases femur, in 4 cases a knee arthrodesis, in 68 cases tibia, in 1 case foot, 6 times ankle-joint arthrodesis, in 6 cases humerus, in 4 cases forearm were infected resulting in bone defects,. In most cases the indication for the Masquelet-technique was low-/incompliance due to higher grade of brain injury and polytrauma followed by difficult soft tissue conditions and problems with segmenttransport. In 2/3 positive microbial detection succeeded at the first operation. Mainly we found difficult to treat bacteria. After treating the infection with radical sequestrectomy, removal of foreign bodies and filling the defect with antibiotic loaded cementspacer and external fixation we removed the spacer in common 6–8 weeks later and filled the defect with autologeous bone graft. Most of the patients needed an internal fixation after removing of the fixex. All patients were examined clinically and radiologically every 4–6 weeks in our outpatient department until full weight bearing, later every 3 Months. Results. in 93 of 112 cases the infection was clinically treated successful. 48 patients are allowed full weight bearing (45 with secondary internal plates). There were 18 recurrences of infection, 3 patients underwent lower limb amputation. Conclusions. For patients with low-/incompliance for various reasons and for those with difficult soft tissue conditions following flaps the masquelet technique is a valuable alternative to normal bone graft or segmenttransport. The stiffness of the new masquelet-bone as a rod seems a problem and internal fixation is necessary