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

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

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

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

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

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

Introduction:. Periprosthetic joint infection (PJI) is a devastating diagnosis that carries a significant rate of associated mortality and places a large burden on health care systems. Treatment protocols often include combined intravenous antibiotics and staged revision surgery with locally-delivered antibiotics via PMMA cement spacers and/or beads. One disadvantage of PMMA is the need for later removal. Antibiotic releasing Calcium Sulphate beads (CaSO. 4. ) have had promising results in revision joint surgery and are absorbable, making later removal unnecessary. We report on use in a tertiary referral centre in the UK and present our initial findings. Methods & Results:. CaSO. 4. beads containing 1 gram of Vancomycin and 240 mg of tobramycin per 10 cc was implanted in 12 patients between August 2012 and December 2012, all having undergone revision joint surgery for PJI. Of these patients; 7 were men and 5 women, mean age was 57 years (range 39–72) with a mean ASA grade of 2 (1–4). Indications were infected Total Hip Replacement (n = 7), infected Total Knee Replacement (n = 4) and infected metal on metal hip resurfacing (n = 1). Three procedures were emergencies, with the remainder being semi-elective procedures. One patient had single-stage revision THR. At latest follow up 10 patients had made a full recovery, with normal function and inflammatory markers. Two patients were awaiting a second stage revision procedure. Mean follow up was 2 months (1–4). Conclusion:. Implantable calcium sulphate beads are a new therapeutic agent for use in periprosthetic infection, with improved drug eluting properties and total absorption radiographically within two to three weeks. This study is the first to report its use in the UK, with encouraging data supporting its use in revision arthroplasty surgery

Introduction. Antibiotic loaded absorbable calcium sulphate beads (ALCSB) are an increasingly popular adjunct in the treatment of musculoskeletal infections including osteomyelitis and peri-prosthetic joint infections (PJI). Limited data exist regarding the clinical indications and biochemical outcomes of ALCSB in PJI cases. Aims. To determine the proportion of organisms that were sensitive to the gentamicin and vancomycin that we add to the ALCSB as a part of our treatment protocol and to determine the prevalence of postoperative hypercalcaemia when used for treatment of hip and knee DAIR (debridement and implant retention) and revision arthroplasty for PJI. Methods. A retrospective review of 160 hip and knee revisions using ALCSB performed between June 2015 and May 2018 at a tertiary unit was performed. 10–40 cc of ALCSB was used for each case containing vancomycin and gentamicin. Data recorded included patient demographics, comorbidities, indication for surgery, operative intervention, microbiological results and serum biochemistry for calcium levels. Results. The cohort consisted of 91 males and 69 females, with a mean age of 69.0 years (21.3 to 93.1) and mean BMI of 34.7(12.6 to 48.1). 56 (35%) had single-stage revision, 45 (28.1%) had first stage revision, 35 (21.9) had DAIR, 19 (11.9%) had second stage revision and 5 (3.1%) other procedures. Organisms included staphylococcus aureus (30.0%), culture-negative (27.5%), staphylococcus epidermidis (18.1%), and pseudomonas aeruginosa (3.1%). 54.3% were sensitive to both vancomycin and gentamicin, 25.0% to vancomycin only and 8.6% to gentamicin only. 11.9% (19/160) of patients had transient post-operative hypercalcaemia (normal range 2.2–2.7mmol/L), peaking at day 6–7 and resolved with hydration by day 10 postoperatively. Preoperatively, 26.9% had albumin <35 g/L and 49.3% had some degree of renal impairment with an eGFR <90 ml/min. Conclusion. The use of ALCSB allows local delivery of vancomycin and gentamicin in lower limb PJI. Organisms were sensitive to this antibiotic combination in 88% cases. Care must be taken to monitor calcium for 10 days post-operatively

The diagnosis of periprosthetic joint infection may be difficult with patients presenting months or years after initial surgery with surgery-associated or haematogenously spread bacteria. Synovasure™ is a new point of care assay that measures alpha defensin produced by activated leucocytes in joints; it is licensed for the diagnosis of periprosthetic joint infections. We sought to include alpha defensin testing in a testing algorithm to improve the diagnosis of periprosthetic joint infection. An algorithm for testing patients with suspected periprosthetic joint infection was developed and agreed among knee surgeons in Gloucestershire, UK. Data was prospectively collected on all tests performed along with information on how the results of the alpha defensin test altered patient management. A sample of joint fluid was taken using aseptic technique in theatre and tested for alpha defensin production at the point of care. Samples were then referred for standard culture and selected samples for 16SrRNA PCR. 12 patients were assayed for alpha defensin in periprosthetic joint fluid during 2015. 7 patients were female, 5 male and ages ranged 64–86 years. 10 patients had a negative point of care alpha defensin test. Only 2 of these patients also had a leukeocyte esterase (LE) test performed and these were negative. The culture results from all samples were negative for both direct and enrichment cultures. 3 samples also had 16SrRNA PCR performed and these were negative. 2 patient samples tested positive for alpha defensin. LE tests were not performed. Both samples were culture negative on direct and enrichment culture however both samples were also referred for 16SrRNA PCR which detected DNA compatible with Staphylococcus caprae/capitis/ saccharolyticus/epidermidis from 1 patient and DNA with homology to Streptococcus gallolyticus/equinusI for the other. Alpha defensin testing improved the diagnosis of prosthetic joint infection. A positive alpha defensin test may be used to select patients for whom 16SrRNA PCR testing is useful in order to maximise the potential for pre-revision infection diagnosis and the planning of appropriate adjuncts such as antibiotic laden cement or calcium sulphate beads. Negative alpha defensin tests on aspirated joint fluid may avoid the need for arthroscopy and biopsy and allow planning for single stage revision surgery without concern for infection

Aim. Dissolvable antibiotic-loaded calcium sulphate beads have been utilized for management of periprosthetic joint infection (PJI) and for aseptic revision arthroplasty. However, wound drainage and toxic reactive synovitis have been substantial problems in prior studies. Currently a commercially pure, physiologic product has been introduced that may reduce complications associated with this treatment modality. We aim to answer the question: does a commercially pure, physiologic version of antibiotic-loaded calcium sulfate beads reduce wound drainage and provide efficacious treatment for PJI and aseptic revision arthroplasty?. Method. Starting January 2010, 756 consecutive procedures were performed utilizing a set protocol of Vancomycin and Tobramycin antibiotics in commercially pure dissolvable antibiotic beads. There were 8 designated study groups:. Aseptic Revision TKA. N = 216. Aseptic Revision THA. N = 185. DECRA. *. TKA. N = 44. DECRA. *. THA. N = 16. 1. st. Stage Resection TKA. N = 103. 1. st. Stage Resection THA. N = 62. Reimplant TKA. N = 81. Reimplant THA. N = 49. *. DECRA = Debridement, modular Exchange, Component Retention, iv Antibiotics for acute PJI. Results. Wound drainage in the entire series was 4.2%. Wound drainage was generally seen in cases using higher bead volumes (≥30cc). The rate of heterotopic ossification was 1.6%. With bead volumes of ≥30cc, we did notice transient hypercalcemia in 12% of the study group (14% hips, 10% knees). The overall rate of infection failure was 2.5%. In the DECRA groups, reinfection failure rate was encouraging, measuring 9.1% in knees and 6.3% in hips. The non-DECRA group with the highest infection rate was Reimplant TKA (6.2%). Conclusions. We utilized a large series of commercially pure dissolvable antibiotic-loaded beads in a wide variety of clinical scenarios in patients with substantial comorbidities. Our rate of wound drainage, compared to prior studies utilizing gypsum products, was reasonably good. Additionally, our infection failure rates were encouraging. Over-stuffing knee joints with too many beads, in our clinical review, does affect wound drainage rates. By removing impurities from calcium sulfate, we do not see the substantial toxic synovial reaction compared to the traditional gypsum-washed products. We feel that commercially pure, physiologic antibiotic-loaded dissolvable beads are an acceptable delivery tool for local antibiotic delivery in aseptic and septic revision joint arthroplasty of the hip and knee. In our opinion, further study is warranted. We advocate future randomized studies to examine the potential of improving outcomes of PJI and aseptic revision arthroplasty

Aims

This study presents patient-reported quality of life (QoL) over the first year following surgical debridement of long bone osteomyelitis. It assesses the bone involvement, antimicrobial options, coverage of soft tissues, and host status (BACH) classification as a prognostic tool and its ability to stratify cases into ‘uncomplicated’ or ‘complex’.