Aims. Calcium sulphate has traditionally been used as a filler of dead space arising during surgery. Various complications have been described following the use of Stimulan bio-absorbable calcium sulphate beads. This study is a prospective observational study to assess the safety profile of these beads when used in revision arthroplasty, comparing the complication rates with those reported in the literature. Methods. A total of 755 patients who underwent 456 revision total knee arthroplasties (TKA) and 299 revision total hip arthroplasties (THA), with a mean follow-up of 35 months (0 to 78) were included in the study. Results. A total of 32 patients (4.2%) had wound drainage, and this was higher with higher bead volumes and in McPherson grade C patients. There was also a significantly higher bead volume in the 41 patients who developed hypercalcaemia, two of which were symptomatic (p < 0.0001). A total of 13 patients (1.7%) had heterotopic ossification (HO). There was no statistically significant relationship between the development of HO and bead volume (p > 0.05). Conclusion. The strength of this study lies in the large number of patients and the detailed data collection, making it the most comprehensive report available in the literature on the use of calcium sulphate-based bone substitutes. Cite this article: R. Kallala, W. Edwin Harris, M. Ibrahim, M. Dipane, E. McPherson. Use of Stimulan absorbable calcium sulphate beads in revision lower limb arthroplasty: Safety profile and complication rates. Bone Joint Res 2018;7:570–579. DOI: 10.1302/2046-3758.710.BJR-2017-0319.R1

Introduction. The purpose of this study was to analyse the efficacy and complications associated with the use of Calcium Sulphate synthetic bone graft in a paediatric population. There are no published articles on the use in children. Materials & Methods. A retrospective review was undertaken of the notes, microbiology, and X-Rays of 17 cases (in 15 patients) of calcium sulphate use in paediatric patients. As well as patient demographic data, data collected included indication, use of additional agents (antibiotics), return to theatre, and wound complications. Major complications were also assessed for. Results. There were 17 cases, in 15 patients, in our case series where calcium sulphate synthetic bone graft was used. The average patient age was 12.0 years (range 5 years – 17 years). Indications for use included likely infection (12), possible infection (3), and 2 elective finger cases (enchondroma and osteotomy). The humerus was the most common target site (5), followed by the femur (4), tibia (3), calcaneum (2), finger (2) and metatarsal (1) also included. There were positive intra-operative microbiology samples for eleven cases (Staphylococcus aureus and Staphylococcus epidermidis). Antibiotics were used in all cases except the elective finger surgery, and choice ranged between vancomycin, gentamicin, or a combination of both. Two patients required return to theatre for management of ongoing deep infection, although one case was later deemed to be non-infective osteomyelitis. Seven patients had undergone debridements prior to the definitive one with calcium sulphate (5 without Calcium Sulphate, 2 with Calcium Sulphate). Three patients experienced wound issues in the form of discharge/leakage, all were managed with dressings and did not require return to theatre. Conclusions. Calcium Sulphate synthetic bone graft, with addition of antibiotics, is an efficacious treatment in the paediatric population and is not associated with any major complications. Wound discharge should be observed for, and patients/parents warned about this, but only as per the adult population

Treatment of periprosthetic joint infection (PJI) can include local delivery of antibiotics. A frequently used medium is absorbable calcium sulphate beads. The aims of this study were to:. identify how often organisms in infected THRs are sensitive to the added antibiotics. establish the incidence of persistent wound discharge and hypercalcaemia. All patients who received an antibiotic loaded calcium sulphate carrier (Stimulan, Biocomposites, Keele, UK) for either confirmed infection, presumed infection or for prophylaxis between July 2015 and July 2020 were included. Stimulan use was at the discretion of the surgeon, and between 10 and 40cc was used. In the absence of a known organism we routinely used 1g vancomycin and 240mg gentamicin per 10 cc of calcium sulphate. Post-operative sensitivities for all organisms cultured were compared to the antibiotics delivered locally. Persistent wound drainage was defined as discharge beyond the third postoperative day. Patients had serum calcium measured if they developed symptoms consistent with hypercalcaemia (Ca >2.6 mmol/L) or the clinical team felt they were at high risk. 189 patients (mean age 66.9 years, mean BMI 28.9, 85 male, 104 female) were included. 11 patients had a native joint septic arthritis, 42 presented with acute PJI and 136 presented with chronic PJI. 133 patients grew an organism, of which 126 were sensitive to the added antibiotics. Of the seven patients with resistant growth five had vancomycin-resistent Enterococcus, one Pseudomonas and one multi-organism growth including coagulase negative Staphylococcus. 40 patients experienced persistent wound discharge, with eight requiring re-operation. All other cases settled with dressing management. 12 patients developed hypercalcaemia (3/64 10cc, 7/117 20cc, 0/2 30cc and 2/6 40cc). The peak calcium reading ranged between the second and twelfth post-operative day. The addition of vancomycin and gentamicin to absorbable calcium sulphate covers the majority of organisms found in culture positive infection in our cohort. It also appears safe, with an acceptable incidence of hypercalcaemia or wound discharge. Further work is required to identify patients at greatest risk of culturing resistant organisms or delayed wound healing

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

Objectives. Bone void fillers are increasingly being used for dead space management in arthroplasty revision surgery. The aim of this study was to investigate the influence of calcium sulphate bone void filler (CS-BVF) on the damage and wear of total knee arthroplasty using experimental wear simulation. Methods. A total of 18 fixed-bearing U2 total knee arthroplasty system implants (United Orthopedic Corp., Hsinchu, Taiwan) were used. Implants challenged with CS-BVF were compared with new implants (negative controls) and those intentionally scratched with a diamond stylus (positive controls) representative of severe surface damage (n = 6 for each experimental group). Three million cycles (MC) of experimental simulation were carried out to simulate a walking gait cycle. Wear of the ultra-high-molecular-weight polyethylene (UHMWPE) tibial inserts was measured gravimetrically, and damage to articulating surfaces was assessed using profilometry. Results. There was no significant difference (p  >  0.05) between the wear rate of implants challenged with CS-BVF (3.3 mm. 3. /MC (95% confidence interval (CI) 1.8 to 4.8)) and the wear rate of those not challenged (2.8 mm. 3. /MC (95% CI 1.3 to 4.3)). However, scratching the cobalt-chrome (CoCr) significantly (p < 0.001) increased the wear rate (20.6 mm. 3. /MC (95% CI 15.5 to 25.7)). The mean surface roughness of implants challenged with CS-BVF was equivalent to negative controls both after damage simulation (p = 0.98) and at the conclusion of the study (p = 0.28). Conclusion. When used close to articulating surfaces, a low-hardness, high-purity CS-BVF had no influence on wear. When trapped between the articulating surfaces of a total knee arthroplasty, CS-BVF did not scratch the surface of CoCr femoral components, nor did it increase the wear of UHMWPE tibial inserts compared with undamaged negative controls. Cite this article: R. M. Cowie, S. S. Aiken, J. J. Cooper, L. M. Jennings. The influence of a calcium sulphate bone void filler on the third-body damage and polyethylene wear of total knee arthroplasty. Bone Joint Res 2019;8:65–72. DOI: 10.1302/2046-3758.82.BJR-2018-0146.R1

Background. Medical grade Calcium Sulphate can be used as a delivery vehicle for antibiotics. We use these for treating patients with established osteomyelitis, but also use it prophylactic for contaminated war injuries, to fill voids in bone with osteo conductve filler that delivers local antibiotics, and can integrate with bone. Although antibiotic loaded calcium sulphate is increasingly used, there is little data to demonstrate that systemic levels generated by local release of antibiotics are safe. For this reason, we routinely assay systemic levels of antibiotics. Objectives. To determine if systemic toxicity occurs after the use of antibiotic loaded calcium sulphate in the treatment of bone and soft tissue infection. Material and Method. Bone cavities and soft tissue dead spaces were aggressively debrided, lavaged and packed with Calcium Sulphate (10–40 cc) loaded with Vancomycin (1–4 g) and Gentamicin (240–960 mg). Post-operatively serial assays of Vancomycin and Gentamicin levels 1 hour after surgery then daily for three days. Renal function was also measured. Results. In patients with normal renal function. : The systemic levels were either un-measurable at the first assay, or below the acceptable trough level (Mean 2.4 and 1.8 for Vancomycin and Gentamycin respectively). They had measurable systemic levels at the third assay . In patients with renal dysfunction. : Systemic levels were in the therapeutic range determined for systemically administered antibiotics, but these levels remained high and did not decrease until patients had undergone their routine dialysis. Conclusions. In patients treated with antibiotic loaded Calcium Sulphate: Antibiotic assays are not necessary in patients who have normal renal function. Patients with impaired renal function should have:. Use lower doses of antibiotics. Should undergo assays routinely. Ensure dialysis after surgery. If they remain high, the antibiotic loaded calcium sulphate could be removed

Objectives. We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells. Materials and Methods. We seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed. To mimic surgical conditions with leakage of extra cellular matrix (ECM) proteins and growth factors, we cultured rat bone cells ROS 17/2.8 in a bioreactor and harvested the secreted proteins. The secretome was added to rat muscle cells L6. The phenotype of the muscle cells after treatment with the media was assessed using immunostaining and light microscopy. Results. C2C12 cells differentiated into osteoblast-like cells expressing prominent bone markers after seeding on the biomaterial. The conditioned media of the ROS 17/2.8 contained bone morphogenetic protein-2 (BMP-2 8.4 ng/mg, standard deviation (. sd. ) 0.8) and BMP-7 (50.6 ng/mg, . sd. 2.2). In vitro, this secretome induced differentiation of skeletal muscle cells L6 towards an osteogenic lineage. Conclusion. Extra cellular matrix proteins and growth factors leaking from a bone cavity, along with a ceramic biomaterial, can synergistically enhance the process of ectopic ossification. The overlaying muscle acts as an osteoinductive niche, and provides the required cells for bone formation. Cite this article: D. B. Raina, A. Gupta, M. M. Petersen, W. Hettwer, M. McNally, M. Tägil, M-H. Zheng, A. Kumar, L. Lidgren. Muscle as an osteoinductive niche for local bone formation with the use of a biphasic calcium sulphate/hydroxyapatite biomaterial. Bone Joint Res 2016;5:500–511. DOI: 10.1302/2046-3758.510.BJR-2016-0133.R1

To assess the performance of calcium sulphate pellets as a bone graft substitute in an Orthopaedic Oncology practice using clinical and radiological outcomes. Between 1998 and 2001, calcium sulphate pellets were used in cavitary defects in 38 procedures in 34 patients with bone tumours. In 29 calcium sulphate pellets were used alone, in 8 allograft and in 1 autograft bone was added. The diagnosis was unicameral bone cyst in 13, giant cell tumour in 11, non-ossifying fibroma in 2, chondroblastoma in 2, benign fibrous histiocytoma in 2 and another pathology in 8 procedures. The femur was involved in 12 procedures, the humerus in 8, the radius in 5, the tibia in 4, the fibula in 3, the calcaneus in 2, and one procedure each in the tarsal cuboid, a metatarsal, the talus, and the middle phalanx of a finger. Median follow up was 14 months (3 to 48). Seven patients had wound complications. Pellets had absorbed completely in 26/28 (93%) evaluable procedures by 3 months. Healing of the defect occurred in 24/28 (86%) evaluable procedures by 6 months. In 6 cases, the healed defect contained cystic areas simulating local recurrence. In 3 cases, there was collapse of the defect. In cavitary defects, calcium sulphate pellets reliably absorb. Some patients have wound complications, especially where the cavity is relatively superficial. The pellets do not provide mechanical stability where there is attenuated cortical bone. Cysts within the healed defect may simulate recurrence

In bone and joint infections, several materials can be used for local antibiotic elution at site of infection. Polymethylmethacrylate (PMMA) cement is often used. Recently the use of antibiotic impregnated dissolvable synthetic pure calcium sulphate beads [Stimulan R]1 has been used as an alternative, due to several perceived advantages. We present our experience of using Calcium sulphate beads in infections involving the upper limb. From Jan 2012 to Jan 2015, we used Calcium sulphate beads in 7 complex upper limb infections including 1 elbow replacement, 2 infected non unions, 2 shoulder replacement, 1 wrist fusion and I ORIF elbow. We used combination of Vancomycin and Gentamicin in the beads, using manufacturer's mixing guide for optimum setting. Arthroplasty infections underwent explantation, addition of antibiotic impregnated calcium sulphate beads in the joint space, followed by a second stage, and systemic antibiotics. Fracture non-union cases had surgical debridement, calcium sulphate beads and systemic antibiotics. Follow up (6months to 2 years) indicate no recurrence of infection in any case. The most common organisms isolated were Coagulase negative staphylococcus and Staphylococcus aureus. Others included Group B Streptococcus, Serratia marscesens and Corynebacterium spp. In 2 of 7 cases there was significant drainage from the wound. This settled without further input. For fracture non-union fixation, there was no need to do second procedure to remove beads as they dissolve. In cases of staged revisions, the beads were inserted at first stage with microbiological clearance at 2nd stage. At present there are no reports in the literature of the use of this product in the upper limb. Our experience suggests use of dissolvable pure Calcium sulphate beads impregnated with selected antibiotics, is an effective adjunct to current treatments. Aseptic drainage has been reported and this was seen in some of our cases. It is postulated that the use of Calcium sulphate beads in more superficial joints may lead to more drainage. It may be necessary to avoid packing any beads in the subcutaneous spaces and using lower volumes in upper limb. Further work will include long-term follow up and any evidence of relapse or recurrence of infection

Aim. To determine if systemic toxicity occurs after the use of antibiotic loaded calcium sulphate in the treatment (1) of bone and soft tissue infection. Although antibiotic loaded calcium sulphate is increasingly used for the local treatment of bone and soft tissue infection, there is little data to demonstrate that systemic levels generated by local release of antibiotics are safe. For this reason, we routinely assay systemic levels of antibiotics. Methods. Patients with osteomyelitis or soft tissue infection underwent surgical debridement and lavage of the infected tissue in routine fashion. Patients with osteomyelitis were graded with the Cierny-Mader classification. Bone cavities and soft tissue dead spaces were packed with antibiotic loaded calcium sulphate (10–40 cc) loaded with Vancomycin (1–4 g) and Gentamicin (240–960 mg). The wounds were closed over the antibiotic loaded calcium sulphate. Patients underwent serial assays of Vancomycin and Gentamicin levels on the day of surgery and the first two post-operative days. Renal function was also measured. Results. 12 limbs in 10 patients were treated for osteomyelitis or soft tissue infection. There was 1 Cierny-Mader grade 1, 3 Cierny-Mader grade 3, and 2 Cierny-Mader grade 4. Two had deep soft tissue infection alone. There were 3 type A hosts and 7 type B hosts. The patients age ranged from 24 to 89 (mean 54). In patients without renal dysfunction, the systemic levels were either unmeasurable at the first assay, or below the acceptable trough level. (Mean 2.4 and 1.8 for Vancomycin and Gentamycin respectively). They had unmeasurable systemic levels at the third assay. In patients with renal dysfunction, systemic levels were in the therapeutic range determined for systemically administered antibiotics, but these levels remained high and did not decrease until patients had undergone their routine dialysis. Conclusions. In patients treated with antibiotic loaded Stimulan, antibiotic assays are not necessary in patients who have normal renal function, as they clear the systemic absorption as quickly as it is generated. Patients with impaired renal function should have lower doses of antibiotic used for their topically applied carrier, and should undergo assays regularly to ascertain if levels are remaining below the accepted range determined for systemically administered antibiotics. If they remain high, the antibiotic loaded calcium sulphate could be removed. * Stimulan (Biocomposites, Keele, UK)

The management of chronic osteomyelitis is fraught with difficulties; a multi-disciplinary team approach is recommended for optimum outcome. Thorough debridement, dead space management and organism targeted antibiotic therapy the gives best clinical results. Calcium sulphate beads impregnated with antibiotic is an absorbable option for prolonged local antibiotic elution and dead space management. This study aims to analyse the early results of single stage management of osteomyelitis with antibiotic impregnated calcium sulphate beads. Following surgical debridement, calcium sulphate impregnated typically with tobramycin and/or vancomycin is inserted to obliterate the dead space. Intravenous antibiotics – typically teicoplanin and piperacillin-tazobactam – are administered until culture results permit rationalisation to narrow spectrum agents. Patients are followed up in Infectious Diseases and Orthopaedic clinics for a period of 12 months and discharged if quiescence is achieved. We conducted a retrospective analysis of our prospective database to identify patients treated with our single stage protocol for chronic osteomyelitis. We excluded patients that had (1) less than 6 months of follow up, (2) incomplete metal-ware removal, (3) patients lost to follow up. Fourteen patients (9 men, 5 women) with mean age of 41 (16–73) years and mean follow up of 9 (6–12) months were included in study. Eleven patients had previous surgeries involving internal fixation; the rest were primary osteomyelitis. Seven patients had washouts and removal of metal-ware procedures for osteomyelitis prior to referral to the bone infection service. Clinical, radiographic, and laboratory (microbiological, biochemical and haematological) methods were used to monitor response to treatment. Cierney-Mader classification determined that 8 patients were classed as type A (normal hosts); 4 as BS (systemically compromised); 2 as BLS (locally and systemically compromised). Anatomic analysis suggested 7 were Type 1 (medullary osteomyelitis); the remaining 7 were type 3 (localised disease). Five patients were staged IA; three each staged IIIA and IIIBS; and one each staged IBs, IBLS, IIIBLS. Staphylococcus Aureus was the commonest causative organism. Follow up radiograph monitoring indicated absorption of the beads by 3 months. There has been no evidence of recurrence based on clinical, radiographic and blood based parameters in all patients. Short-term results of single stage osteomyelitis treatment with calcium sulphate beads impregnated with antibiotics are promising

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

Aims. There is a considerable challenge in treating bone infections and orthopaedic device-associated infection (ODAI), partly due to impaired penetration of systemically administrated antibiotics at the site of infection. This may be circumvented by local drug administration. Knowledge of the release kinetics from any carrier material is essential for proper application. Ceftriaxone shows a particular constant release from calcium sulphate (CaSO. 4. ) in vitro, and is particularly effective against streptococci and a large portion of Gram-negative bacteria. We present the clinical release kinetics of ceftriaxone-loaded CaSO. 4. applied locally to treat ODAI. Methods. A total of 30 operations with ceftriaxone-loaded CaSO. 4. had been performed in 28 patients. Ceftriaxone was applied as a single local antibiotic in 21 operations and combined with vancomycin in eight operations, and in an additional operation with vancomycin and amphotericin B. Sampling of wound fluid was performed from drains or aspirations. Ceftriaxone concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results. A total of 37 wound fluid concentrations from 16 operations performed in 14 patients were collected. The ceftriaxone concentrations remained approximately within a range of 100 to 200 mg/l up to three weeks. The median concentration was 108.9 mg/l (interquartile range 98.8 to 142.5) within the first ten days. No systemic adverse reactions were observed. Conclusion. Our study highlights new clinical data of locally administered ceftriaxone with CaSO. 4. as carrier material. The near-constant release of ceftriaxone from CaSO. 4. observed in vitro could be confirmed in vivo. The concentrations remained below known local toxicity thresholds. Cite this article: Bone Joint Res 2022;11(11):835–842

Periprosthetic joint infection (PJI) is a devastating complication for patients and results in greatly increased costs of care for both healthcare providers and patients. More than 15 500 revision hip and knee procedures were recorded in England, Wales and Northern Ireland in 2013, with infection accounting for 13% of revision hip and 23% of revision knee procedures. We report our experience of using antibiotic eluting absorbable calcium sulphate beads in 15 patients (eight men and seven women with a mean age of 64.8 years; 41 to 83) as part of a treatment protocol for PJI in revision arthroplasty. . The mean follow-up was 16 months (12 to 22). We report the outcomes and complications, highlighting the risk of hypercalcaemia which occurred in three patients. We recommend that serum levels of calcium be routinely sought following the implantation of absorbable calcium sulphate beads in orthopaedic surgery. Cite this article: Bone Joint J 2015;97-B:1237–41

Introduction: Purified plaster of Paris can be used as a resorbable carrier material for local antibiotic therapy. Clinical use already has been published with vancomycin and the aminoglycosides gentamycin and tobramycin. Calcium sulphate pellets with vancomycin can be manufactured during operation from Osteoset. ®. and vancomycin powder, whereas calcium sulphate with tobramycin is available as ready-to-use pellets under the brand name Osteoset T. ®. Results are promising. However, no data on systemic serum levels in humans have been published so far, despite well known toxicity issues of these antibiotics in systemic therapy. Methods: Following implantation of calcium sulphate with vancomycin or tobramycin, systemic serum levels of these antibiotics have been measured for up to 10 days, and prospectively gathered. Considering serum levels and renal function, pharmacokinetics have been estimated. Results: Between August 2006 and February 2008, calcium sulphate with vancomycin has been implanted in 15 patients, and with tobramycin in 12 patients. Whereas vancomycin levels remained very low, tobramycin levels close to the usually accepted trough levels could be observed at 24h post-operation. Conclusion: Vancomycin added to calcium sulphate has a safe systemic profile. On the contrary, significant serum levels of tobramycin can be measured more than 24h after implantation. Caution is mandatory when using this antibiotic, and explantation should be considered if levels too high are observed

Calcium sulphate is now a proven adjunct to the replenishment of bone stock in joint replacement surgery. Alone and as a composite, it has been used successfully for many years in both dental and orthopaedic applications. OsteoSet (Wright Medical Technology), a processed, purified material, has been used as a bone void filler in 51 revision total hip arthroplasty (THA) procedures. Follow-up of these cases ranges from 3 to 48 months. Radiographs show that the calcium sulphate has disappeared in all cases. In all but three patients, all of whom had failure of the acetabular component or infection, the calcium sulphate has been replaced with what appears to be trabeculated cancellous bone. Clinical results for cases that did not have mechanical failure or infection are indistinguishable from any revision THA in which the acetabular component is well fixed. Implantation of the calcium sulphate pellets calls for preparation of a well vascularised bed. The pellets are placed in such a way that load is not transferred to them from the implanted acetabular component. Rather, the load should be transferred from the acetabular component directly to host bone. Postoperatively, load bearing is limited for at least eight weeks and for longer of the quality of the supporting bone is poor

We performed a prospective audit to assess radiological and clinical sequelae of using injectable calcium sulphate in the management of distal radial fractures. All patients in a 4-month period who were treated with injectable calcium sulphate for distal radial fracture were included in the audit. Initial data was collected on demographics; AO classification and degree of deformity; method of fixation and surgical complications. Follow up consisted of clinical and radiological assessment of fracture healing at standard fracture clinic intervals with a final assessment of subjective functional recovery. 16 patients were included in the audit, all of whom were followed up for a minimum of 8 weeks. We observed a low incidence of secondary displacement, and did not observe the problem of increased pain and erythema that has been observed with other bone graft substitutes. We conclude that injectable calcium sulphate is a useful adjunct to conventional management of these fractures that is safe, helps maintain fracture reduction and is not associated with product specific complications

We describe a case series using calcium sulphate bio composite with antibiotics (Cerament/Stimulan) in treating infected metalwork in the lower limb. Eight patients aged 22–74 (7 males, 1 female) presented with clinical evidence of infected limb metal work from previous orthopaedic surgery. Metal work removal with application of either cerement in 5 cases (10–20ml including 175mg–350mg gentamycin) or stimulan in 3 cases (10–20ml including either 1g vancomycin or clindamycin 1.2g or 100mg tigecycline) into the site was performed. Supplemental systemic antibiotic therapy (oral/intravenous) was instituted based on intraoperative tissue culture and sensitivity. Four patients had infected ankle metalwork, 2 patients infected distal tibial metalwork and 2 had infected external fixators. Metal work was removed in all cases. The mean pre operative CRP was 15.8mg/l (range 1–56mg/l). The mean postoperative CRP at 1 month was 20.5mg/l (range 2–98mg/l). The mean pre op WCC was 7.9×10. 9. (range 4.7–10.5 ×10. 9. ). Mean post op WCC at 1 month was 7.1×10. 9. (range 5.0–9.2×10. 9. ). The organisms cultured included enterobacter, staphylococcus aureus, staphylococcus epidermidis, staphylococcus cohnii, stenotrophomonas, acinetobacter, group B streptococcus, enterococcus and escherichia coli. No additional procedures were required in any case. All surgical wounds went on to heal uneventfully. Infection control and union was achieved both clinically and radiologically in all cases. Our results support the use of a calcium sulphate bio composite with antibiotic as an adjuvant for effective local infection control in cases with implant related bone sepsis. The technique is well tolerated with no systemic or local side effects. We believe that implant removal, debridement and local antibiotic delivery can minimise the need for prolonged systemic antibiotic therapy in such cases

A multimodality approach is needed for management of infected joint replacement prostheses and infected skeletal metalwork. We present our results in six patients managed surgically with standard techniques, with the addition of a local antibiotic delivery system using absorbable Calcium Sulphate beads. A retrospective study was undertaken of 6 patients with established musculoskeletal infection in relation to existing metalwork. Two patients had infection in the hip replacement prosthesis, three had infected prosthetic knee joints and one had infection in a femoral locking plate. All were treated with extensive debridement, revision / retention of implants, parenteral antibiotics and local antibiotics. Patients were followed up in clinic for resolution of inflammatory markers and subsidence of signs of infection. Control of infection was achieved in five patients at average 19 months followup. One patient had persistent infection and has undergone further surgery. In this preliminary study, we found local antibiotic delivery using absorbable calcium sulphate beads to be an effective adjuvant to standard debridement, parenteral antibiotics and revision of implants

Bone and joint infections of the lower limbs cause significant morbidity for patients. Infection is a devastating complication for prosthetic joint replacements. In this large case series from a single centre in the NE of England, we present our experience of using antibiotic impregnated dissolvable synthetic pure calcium sulphate beads [Stimulan R]1 for local elution of antibiotics at the site of infection. At our centre, from August 2012 to Jan 2015, antibiotic impregnated dissolvable synthetic pure calcium sulphate beads [Stimulan R]1 was used for local elution of antibiotics in 45 patients with lower limb bone or joint infections. Tailored plans were made by Orthopedic surgeon and Microbiologist MDTs based on bacteria and sensitivities. Cases included 20 THR, 13 TKR, 5 Hemiarthroplasties, 4 tibial nonunions, 1 infected femoral plate and 2 paediatric osteomyelitis. Organisms isolated – Coagulase negative Staphs, Staph aureus, MRSA, E coli, Enterococcus, Enterobacter cloacae, Serratia and 1 Salmonella typhimurium!!. In our cases, a combination of Vancomycin and Gentamicin was added to Stimulan beads following manufacturer's mixing guide. In 2 cases, we added Ceftazidime to the beads and Daptomycin in 1 case. In bone infections, surgical debridement and systemic antibiotics were also needed. All arthroplasty infections underwent explantation with addition of antibiotic impregnated beads either at single stage or both stages of 2 stage revisions and systemic antibiotics. Follow up (ranging 9months to 2 years) indicates no failure so far. The beads caused no excessive wound drainage. There was no need to remove beads as they dissolve. In the cases where a staged revision was performed, the beads were inserted at first stage and there was microbiological clearance of infection at 2nd stage. Our series includes some experince in paediatric cases too. As far as we are aware, this is the largest series in the UK from a single centre reporting experience with Stimulan in infected bone and joints of the lower limbs. Our experience suggests use of dissolvable pure Calcium sulphate beads impregnated with carefully selected antibiotics, works as an effective adjunct to current treatments and offers flexibility with choice of antiobiotics that can be added locally. Acknowledgements. Biocomposites UK for supporting attendance at EBJIS. Authors control ownership of all data and analysis