Aims. The use of local antibiotic carriers in the treatment of chronic osteomyelitis is an important adjunct in dead space management. We present the outcomes of two different biodegradable antibiotic carriers used in the management of chronic osteomyelitis. Method. A single centre series between 2006–2017. The initial cohort (2006–2010) of 137 cases, Group A, had Osteoset® T (calcium sulphate carrier containing tobramycin). The second cohort (2013–1017) of 160 cases, group B, had CeramentTM G (biphasic calcium sulphate, nano-crystalline hydroxyapatite carrier containing gentamicin). Only Cierny-Mader Grade III and IV cases were included with a minimum six-month radiographic follow-up. Infection recurrence rate, wound leakage, subsequent fracture involving the treated segment, and radiographic void filling were assessed at a minimum of 6 months following surgery. Results. Mean follow-up in Group A was 2.5 yrs (0.5–10.5) and in Group B it was 1.4 yrs (0.6–4.7). Group A had a significantly higher rate of infection recurrence (16/137 (11.7%) Vs. 7/160 (4.4%) p=0.0278), wound leakage (26/137 (19.0%) Vs. 16/160 (10.0%) p=0.0304) and subsequent fracture rate (11/137 (8.0%) Vs. 3/160 (1.9%) p=0.0143) compared to Group B. Average time to recurrence was 1.07 years (0.1–2.6) in Group A and 1.02 (0.2–2.1) in Group B. The mean bone void healing in Group B was significantly better than Group A (73.2% Vs. 40.0%, p <0.00001). Conclusions. Cerament™ G has significantly better bone healing compared to a calcium sulphate carrier and was associated with a lower rate of recurrent infection, wound leakage and subsequent fracture risk

Systemic antibiotics reduce infection in open fractures. Local delivery of antibiotics can provide higher doses to wounds without toxic systemic effects. This study investigated the effect on infection of combining systemic with local antibiotics via polymethylmethacrylate (PMMA) beads or gel delivery. An established Staphylococcus aureus contaminated fracture model in rats was used. Wounds were debrided and irrigated six hours after contamination and animals assigned to one of three groups, all of which received systemic antibiotics. One group had local delivery via antibiotic gel, another PMMA beads and the control group received no local antibiotics. After two weeks, bacterial levels were quantified. . Combined local and systemic antibiotics were superior to systemic antibiotics alone at reducing the quantity of bacteria recoverable from each group (p = 0.002 for gel; p = 0.032 for beads). There was no difference in the bacterial counts between bead and gel delivery (p = 0.62). . These results suggest that local antibiotics augment the antimicrobial effect of systemic antibiotics. Although no significant difference was found between vehicles, gel delivery offers technical advantages with its biodegradable nature, ability to conform to wound shape and to deliver increased doses. Further study is required to see if the gel delivery system has a clinical role. Cite this article: Bone Joint J 2015;97-B:1423–7

Aims. Musculoskeletal infection is a devastating complication in both trauma and elective orthopaedic surgeries that can result in significant morbidity. Aim of this study was to assess the effectiveness and complications of local antibiotic impregnated dissolvable synthetic calcium sulphate beads (Stimulan Rapid Cure) in the hands of different surgeons from multiple centres in surgically managed bone and joint infections. Methods. Between January 2019 and December 2022, 106 patients with bone and joint infections were treated by five surgeons in five hospitals. Surgical debridement and calcium sulphate bead insertion was performed for local elution of antibiotics in high concentration. In all, 100 patients were available for follow-up at regular intervals. Choice of antibiotic was tailor made for each patient in consultation with microbiologist based on the organism grown on culture and the sensitivity. In majority of our cases, we used a combination of vancomycin and culture sensitive heat stable antibiotic after a thorough debridement of the site. Primary wound closure was achieved in 99 patients and a split skin graft closure was done in one patient. Mean follow-up was 20 months (12 to 30). Results. Overall, six out of 106 patients (5.6%) presented with sepsis and poorly controlled comorbid conditions, and died in the hospital within few days of index surgery. Out of the remaining 100 patients, control of infection was achieved in 95 patients (95%). Persistence of infection was noted in five (5%) patients. Out of these 95 patients that had good control of infection, four patients (4.2%) with gap nonunion needed Masquelet procedure to achieve union. Conclusion. Our multicentre experience confirmed that surgical debridement along with calcium sulphate bead insertion was effective in treating bone and joint infections without any side effects and complications. Cite this article: Bone Jt Open 2023;4(7):516–522

Aim. Previous studies of primary internal fixation of infected non-unions have reported high failure rates. Local antibiotic carriers and coatings have been advocated to reduce infection around implants and allow bone healing. We evaluated the effect of a calcium sulphate/hydroxyapatite antibiotic-loaded composite on bone healing and the eradication of infection in combination with internal fixation. Method. Twelve cases of established infected non-union, with segmental bone loss of up to 1cm were treated using a multidisciplinary protocol. This included; excision, deep sampling, stabilisation, local and systemic antibiotics, and soft-tissue closure. We treated 5 femurs, 4 humeri, 1 tibia and 2 periarticular non-unions at the ankle. Mean age was 59.8 years (34–75) and 9 patients had systemic co-morbidities (C-M Type B hosts). 9 patients had single stage surgery, with 5 IM Nails and 4 plates. Three patients had planned second stage internal fixation after external fixation to correct deformity. Staph. aureus was the commonest pathogen (5 cases) with polymicrobial infection in 3 cases. Results. All 12 patients were infection-free at a mean follow-up of 23 months (range 13–34 months). Union was achieved in 11/12 (92%) with the primary surgery alone. The single failure was the tibial case, who remains with an infection-free, stiff non-union. Conclusion. This protocol offered good results, mainly with a single stage treatment. Primary internal fixation was possible in 9 cases, without recurrent infection. The combination of excision of infected dead bone and a high level of local antibiotics above the Minimum Inhibitory Concentration and Minimum Biofilm Eradication Concentration levels for common bacteria, allowed a high success rate in these difficult cases

Objectives. Deep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing. The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets. DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory. Materials and Methods. We present a new biphasic ceramic bone substitute consisting of hydroxyapatite and calcium sulphate for local antibiotic delivery in combination with bone regeneration. Gentamicin release was measured in four setups: 1) in vitro elution in Ringer’s solution; 2) local elution in patients treated for trochanteric hip fractures or uncemented hip revisions; 3) local elution in patients treated with a bone tumour resection; and 4) local elution in patients treated surgically for chronic corticomedullary osteomyelitis. Results. The release pattern in vitro was comparable with the obtained release in the patient studies. No recurrence was detected in the osteomyelitis group at latest follow-up (minimum 1.5 years). Conclusions. This new biphasic bone substitute containing antibiotics provides safe prevention of bone infections in a range of clinical situations. The in vitro test method predicts the in vivo performance and makes it a reliable tool in the development of future antibiotic-eluting bone-regenerating materials. Cite this article: M. Stravinskas, P. Horstmann, J. Ferguson, W. Hettwer, M. Nilsson, S. Tarasevicius, M. M. Petersen, M. A. McNally, L. Lidgren. Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute: In vitro and clinical release studies. Bone Joint Res 2016;5:427–435. DOI: 10.1302/2046-3758.59.BJR-2016-0108.R1

Introduction. Calcium sulphate is a resorbable void filler that can be used for local antibiotic delivery. Results from clinical studies on chronic osteomyelitis thus treated with local vancomycin have already been published. Despite significant exposure to this drug, there are no pharmacokinetic studies published so far. Based on observations in our patients, a model predicting vancomycin serum and wound fluid levels and toxicity potential is presented. Methods. Following implantation of Osteoset® added with vancomycin, serum and wound fluid concentrations of this antibiotic have been monitored systematically. The pharmacokinetic analysis was performed using a non-linear mixed-effects model based on a one-compartment model with first-degree absorption. Results. Data from 43 patients treated between October 2006 and August 2010 were analysed. Serum concentrations remained far below the usually accepted trough levels of 10 mg/L, and were still acceptable in two cases of post-operative renal failure. Wound fluid concentrations around 1,000 mg/l were observed for the first 7–10 days, and remained above usual minimal inhibitory concentrations for approximately a month. Discussion and Conclusion. This is the first pharmacokinetic exploration of calcium sulphate added with vancomycin for local antibiotic therapy. The systemic exposure to vancomycin is low and appears safe even after implantation of up to 6 g vancomycin, except in case of markedly impaired renal function. Wound fluid concentrations of vancomycin appear extremely interesting for further studies

Aims. Demineralised bone matrix (DBM) is rarely used for the local delivery of prophylactic antibiotics. Our aim, in this study, was to show that a graft with a bioactive glass and DBM combination, which is currently available for clinical use, can be loaded with tobramycin and release levels of antibiotic greater than the minimum inhibitory concentration for Staphylococcus aureus without interfering with the bone healing properties of the graft, thus protecting the graft and surrounding tissues from infection. Materials and Methods. Antibiotic was loaded into a graft and subsequently evaluated for drug elution kinetics and the inhibition of bacterial growth. A rat femoral condylar plug model was used to determine the effect of the graft, loaded with antibiotic, on bone healing. Results. We found that tobramycin loaded into a graft composed of bioglass and DBM eluted antibiotic above the minimum inhibitory concentration for three days in vitro. It was also found that the antibiotic loaded into the graft produced no adverse effects on the bone healing properties of the DBM at a lower level of antibiotic. Conclusion. This antibiotic-loaded bone void filler may represent a promising option for the delivery of local antibiotics in orthopaedic surgery. Cite this article: Bone Joint J 2016;98-B:1126–31

Introduction. Hip and knee arthroplasty present surgeons with difficult bone loss. In these cases the use of morselized allograft is a well established way of optimizing early implant fixation. In revisions, the surgical field is potentially infected. The use of allograft bone creates a “dead space” in which the immune system has impaired access, and even a small amount of bacteria may therefore theoretically increase the risk of infection. In vivo studies have shown that allograft bone is suitable as a vehicle of local antibiotic delivery. We hypothesized that the allograft bone could be used as a local antibiotic delivery vehicle without impairing the implant fixation, tested by mechanical push-out. Material and Methods. Following approval of the Institutional Animal Care and use Committee we implanted a cylindrical (10×6 mm) porous-coated Ti implant in each distal femur of 12 dogs observed for 4 weeks. The implants were surrounded by a circumferential gap of 2.5 mm impacted with a standardized volume of morselized allograft. In the two intervention groups, 0.2ml tobramycin solution of high (800mg/ml) and low (200mg/ml) concentration was added to the allograft, respectively. In the control group 0.2ml saline was added to the allograft. ANOVA-test was applied followed by paired t-test where appropriate. A p-value < 0,05 was considered statistically significant. Results. The impregnation of allograft bone revealed a relative decrease in biomechanical fixation. The decrease was higher in the high dose group than in the low dose group. The most extreme difference was a decrease in strength by 18% (P = 0,511), stiffness 15% (P = 0,135) and energy absorption 27% (P = 0,784). Conclusion. The result shows a trend towards a decrease in implant fixation correlating with the antibiotic concentration. Although the results are not statistically significant the use of antibiotic impregnation should be used with caution until further reaserch has been conducted

Objectives. The purpose of this study was to refine an accepted contaminated rat femur defect model to result in an infection rate of approximately 50%. This threshold will allow examination of treatments aimed at reducing infection in open fractures with less risk of type II error. Methods . Defects were created in the stablised femurs of anaethetised rats, contaminated with Staphylococcus aureus and then debrided and irrigated six hours later. After 14 days, the bone and implants were harvested for separate microbiological analysis. This basic model was developed in several studies by varying the quantity of bacterial inoculation, introducing various doses of systemic antibiotics with and without local antibiotics. Results . The bacterial inoculation associated with a 50% infection rate was established as 1 × 10. 2. colony forming units (CFU). With an initial bacterial inoculum of 1 × 10. 5. CFU, the dose of systemic antibiotics associated with 50% infection was 5 mg/Kg of cafazolin injected sub-cutaneously every 12 hours, starting at the time of the first debridment and continuing for 72 hours (seven doses). The systemic dose of cafazolin was lowered to 2 mg/Kg when antibiotic polymethyl methacrylate beads were used concurrently with the same amount of bacterial inoculation. Conclusion. This model of open fracture infection has been further refined with potential for local and systemic antibiotics. This is a versatile model and with the concepts presented herein, it can be modified to evaluate various emerging therapies and concepts for open fractures. Cite this article: Bone Joint Res 2014;3:187–92

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

Aim. Simultaneous application of Ilizarov frames and free muscle flaps to treat osteomyelitis or infected non-unions is currently not standard practice in the UK, in part related to logistical issues, surgical duration and challenging access for microvascular anastomosis. We present the outcomes for 56 such patients. Methods. Retrospective single centre consecutive series between 2005–2017. We recorded comorbidities, Cierny-Mader and Weber-Cech classification, the Ilizarov method used, flap and anastomosis used, follow-up duration, time to union and complications. Results. 56 patients (55 tibiae and 1 forearm) were included (mean age 48 years). Thirty-four cases had osteomyelitis (20/34 Cierny-Mader Stage IV) and 22 had an infected non-union (14/22 Weber-Cech Type E or F). Forty-six patients had a segmental defect after resection. Monofocal compression was used in 14, monofocal distraction in 15, bifocal compression/distraction in 8, bone transport in 9 and a protective frame in 10. 8/56 had an ankle fusion, 7/56 had an angular deformity corrected at the same time and 32 also had local antibiotic carrier inserted. Forty-six gracilis, 9 latissimus dorsi and 1 rectus abdominus flaps were used. Six cases required urgent flap re-exploration (5 anastomotic revisions and 1 haematoma washout) with 4/6 successfully salvaged. Two cases suffered total flap failure (3.6%). Both had successful revision free muscle flaps with the frame in situ at 10 and 16 days respectively. There were no partial flap failures and no failures in bone transport frames. Mean follow-up was 22 months (4–89). Excluding three cases that still have a frame on, 42/43 (97.7%) achieved bony union. Recurrence of infection occurred in 8.9%. All were infection free at final follow-up after further surgery. Conclusions. With the right expertise, simultaneous Ilizarov frame and free muscle flap is safe and effective in treating complex limb infection, and is not associated with an increased flap failure rate. Level of evidence. III

Aims

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

Aims

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

Background:. In 1931, Gaenslen reported treatment of haematogenous calcaneal osteomyelitis through an incision on the sole of the heel, without the use of antibiotics. We have modified his approach to allow shorter healing times and early mobilisation in a modern series of cases. Method:. Sixteen patients with Cierny-Mader Stage IIIB chronic osteomyelitis were treated with split-heel incision, calcaneal osteotomy, radical excision, local antibiotics, direct skin closure and parenteral antibiotics. 4 patients had diabetic foot infection with neuropathy, 5 had infection after open injuries, 4 had haematogenous osteomyelitis and 3 had Grade 4 pressure ulceration with bone involvement. 14 had sinuses/ulcers and 12 had undergone previous surgery. Primary outcomes were eradication of infection, time to sinus/ulcer healing, mobility and need for modified shoes. Results:. Mean hospital stay was 19.2 days (7–44). 14 patients had no recurrence of infection at final follow-up (minimum 12 months; mean 53 months). Ulcers healed between 4 and 15 weeks. 2 patients with recurrent infection required amputation. Of the 14 salvaged patients, 10 mobilised unaided. 9 required modified shoes. Conclusion:. This protocol gave effective control of infection, ulcer healing and mobilisation within an acceptable time, but amputation remains a risk

Background:. – A multidisciplinary approach is essential to treat chronic osteomyelitis. Surgical debridement of macroscopic infection precedes targeted antibiotics to eradicate microscopic infection. This study analyses early results of our single-stage protocol for chronic osteomyelitis using antibiotic-impregnated calcium sulphate beads (Stimulan). Methods:. – We retrospectively analysed patients with primary or secondary chronic osteomyelitis treated with Stimulan. Patients with incomplete metal-work removal or follow up less than 3 months were excluded. Our study focused on 15 patients (10 male) with an average age of 40.5 years (16–73 years), average follow up of 10.6 months (3 – 21 months). There were 12 cases of secondary osteomyelitis (3 primary). Majority of cases involved the tibia, femur or humerus. Following debridement Stimulan mixed with Vancomycin and/or tobramycin was placed to obliterate dead space and deliver local antibiotics. Intravenous antibiotics, typically piperacillin/tazobactam and/or teicoplanin, were administered post-operatively until tissue culture results were known – rationalised long term antibiotic regimen followed thereafter. Results:. – Staphylococcus aureus was the commonest organism. Follow up monitoring indicated absorption of Stimulan typically by 3 months and no evidence of recurrence based on clinical, radiographic and biochemical parameters. Conclusion:. – Single stage osteomyelitis treatment with Stimulan shows early promising results, is cost effective and decreases the morbidity of further surgery

Aims

There is increasing evidence to support the use of topical antibiotics to prevent surgical site infections. Although previous research suggests a minimal nephrotoxic risk with a single dose of vancomycin powder, fracture patients often require multiple procedures and receive additional doses of topical antibiotics. We aimed to determine if cumulative doses of intrawound vancomycin or tobramycin powder for infection prophylaxis increased the risk of drug-induced acute kidney injury (AKI) among fracture patients.

Aims

This study aimed to investigate the role of quantitative histological analysis in the diagnosis of fracture-related infection (FRI).

Aims

A fracture of the hip is the most common serious orthopaedic injury, and surgical site infection (SSI) is one of the most significant complications, resulting in increased mortality, prolonged hospital stay and often the need for further surgery. Our aim was to determine whether high dose dual antibiotic impregnated bone cement decreases the rate of infection.

Aims

The management of open lower limb fractures in the United Kingdom has evolved over the last ten years with the introduction of major trauma networks (MTNs), the publication of standards of care and the wide acceptance of a combined orthopaedic and plastic surgical approach to management. The aims of this study were to report recent changes in outcome of open tibial fractures following the implementation of these changes.

We undertook a retrospective case-control study to assess the clinical variables associated with infections in open fractures. A total of 1492 open fractures were retrieved; these were Gustilo and Anderson grade I in 663 (44.4%), grade II in 370 (24.8%), grade III in 310 (20.8%) and unclassifiable in 149 (10.0%). The median duration of prophylaxis was three days (interquartile range (IQR) 1 to 3), and the median number of surgical interventions was two (1 to 9). We identified 54 infections (3.6%) occurring at a median of ten days (IQR 5 to 20) after trauma. Pathogens intrinsically resistant to the empirical antibiotic regimen used (enterococci, Enterobacter spp, Pseudomonas spp) were documented in 35 of 49 cases (71%). In multivariable regression analyses, grade III fractures and vascular injury or compartment syndrome were significantly associated with infection. Overall, compared with one day of antibiotic treatment, two to three days (odds ratio (OR) 0.6 (95% confidence interval (CI) 0.2 to 2.0)), four to five days (OR 1.2 (95% CI 0.3 to 4.9)), or > five days (OR 1.4 (95% CI 0.4 to 4.4)) did not show any significant differences in the infection risk. These results were similar when multivariable analysis was performed for grade III fractures only (OR 0.3 (95% CI 0.1 to 3.4); OR 0.6 (95% CI 0.2 to 2.1); and OR 1.7 (95% CI 0.5 to 6.2), respectively).

Infection in open fractures is related to the extent of tissue damage but not to the duration of prophylactic antibiotic therapy. Even for grade III fractures, a one-day course of prophylactic antibiotics might be as effective as prolonged prophylaxis.

Cite this article: Bone Joint J 2013;95-B:831–7.