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. Methods. This cohort study was a secondary analysis of single-centre Program of Randomized Trials to Evaluate Pre-operative Antiseptic Skin Solutions in Orthopaedic Trauma (PREP-IT) trial data. We included patients with a surgically treated appendicular fracture. The primary outcome was drug-induced AKI. The odds of AKI per gram of vancomycin or tobramycin powder were calculated using Bayesian regression models, which adjusted for measured confounders and accounted for the interactive effects of vancomycin and tobramycin. Results. Of the 782 included patients (mean age 48 years (SD 20); 59% male), 83% (n = 648) received at least one vancomycin dose (cumulative range 1 to 12 g). Overall, 45% of the sample received at least one tobramycin dose (cumulative range 1.2 to 9.6 g). Drug-induced AKI occurred in ten patients (1.2%). No association was found between the cumulative dose of vancomycin and drug-induced AKI (odds ratio (OR) 1.08 (95% credible interval (CrI) 0.52 to 2.14)). Additional doses of tobramycin were associated with a three-fold increase in the adjusted odds of drug-induced AKI (OR 3.66 (95% CrI 1.71 to 8.49)). Specifically, the risk of drug-induced AKI rose substantially after 4.8 g of tobramycin powder (7.5% (95% CrI 1.0 to 35.3)). Conclusion. Cumulative doses of vancomycin were not associated with an increased risk of drug-induced AKI among fracture patients. While the risk of drug-induced AKI remains less than 4% with three or fewer 1.2 g tobramycin doses, the estimated risk increases substantially to 8% after four cumulative doses. Level of evidence: Therapeutic Level III. Cite this article: Bone Jt Open 2022;3(4):284–290

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

Objective. To assess the beneficial use of polypropylene mesh impregnated with vancomycin in an experimental model open fractures Gustilo IIIa in rabbits. Material and Method. We worked with 15 New Zeland White rabbits. All of them were carried out under general anaesthetic, a 5-cm incision longitudinal was made at the back of the right thigh. The femur was aproached and a fracture was performed with a shear, giving rise to a multifragment fracture. The wound remained open for 6 hours with the bone exposed, in a non-surgical ambient. Subsequently underwent surgical cleaning of the open fractures in two stages. The fracture was stabilized with an intramedular pin. The animals were sorted in 3 different therapeutic groups:. Group 1: (5 rabbits) without other treatment. Group 2: (5 rabbits) a polypropylene mesh was placed around the fracture. Group 3: (5 rabbits) a polypropylene mesh with vancomycin was placed around the fracture. The wound was closed with nylon stiches. Three weeks postoperative, the animals were intervened surgically under general anesthesia, after aseptic cure and placement of surgical fields, femoral bone biopsies, soft tissue and mesh were taken. The rabbits were sacrified. The samples were sent to pathology and bacteriology labs. Results. The bacteria isolated were as follows: Escherichia coli, Pasteurella multocida, Staphylococcus spp., Clostridium spp. Mamheinia spp. The Clostridium spp. is a common contaminant in the exposed fractures present in the environment. The Pasteurella mustocida is a microorganism present in the oral cavity of rabbits, as well as Escherichia coli is a germ present in the animal's digestive tract. Mannheimia spp. It is a beta-hemolytic organism, found in the nasal flora of these animals and their pathological role is not elucidated. Staphylococcus spp. is a germ that is found in the normal flora of the animals skin. Group 1 showed a relative risk for an infection. For Group 2 the relative risk was substantially greater than 1.4, while in Group 3, the relative risk was 0.6, significantly lower than the previous two groups. The results have shown a beneficial effect of the use of impregnated polypropylene mesh with vancomycin in this animal group. Conclusion. The use of polypropylene meshes with vancomycin could be useful in the treatment of muscle and ligamentary deficits in patients with open fractures Gustillo IIIa

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

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

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.

Introduction. Despite the routine use of irrigation, debridement and systemic antibiotics, there is a high incidence of infection in severe open fractures. The synergistic use of local and systemic antibiotics appreciably reduces infection rates although the time window within which this is effective is unknown. The aim was to determine if delaying treatment of wounds causes higher levels of infection. Methods. A defect was created in the femurs of 90 Sprague-Dawley rats and inoculated with 105CFUs Staphylococcus aureus. At 2, 6 and 24 hours following contamination, the defect was irrigated and debrided. The experimental groups had either vancomycin or tobramycin impregnated PMMA beads placed within the segmental defect. The controls received no further treatment. Two weeks after wound closure, the bacteria within the femur were quantified. Results. Delaying irrigation and debridement resulted in significantly more bacteria (p<0.01) within the control group (2 hr < 6 hr <24 hr). Both locally delivered tobramycin and vancomycin significantly reduced the bacteria (p<0.05) when administered at the earlier time points (2 and 6 hours). Locally-delivered antibiotics were ineffective when delivered at 24 hours. Conclusion. Delaying treatment of contaminated defects reduces its effectiveness to eradicate infection. This is presumably because of the biofilm formation by the bacteria. Biofilms begin to form within a couple of hours and are mature within 12 hours. Early treatment of the wound allows the surgeon to physically remove the bacteria or have antibiotics present before a mature biofilm protects the bacteria

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

Introduction:. The developing world often lacks the resources to effectively treat the most serious injuries, potentially resulting in severe complications of orthopaedic trauma, including osteomyelitis following open fractures or surgical fracture treatment. Antibiotic cement beads are now a widely accepted method of delivering antibiotics locally to the infected area following trauma. This study is based in Cambodia, a low income country struggling to recover from a recent genocide. Aims:. This project studied the effectiveness of locally made antibiotic beads, analysing their effectiveness after being gas sterilised, packaged and kept in storage. Methods:. Different antibiotic beads were manufactured locally using Simplex cement and tested against MRSA bacteria grown from a case of osteomyelitis. Each antibiotic was tested before and after a process of gas sterilisation as well as later being tested after storage in packaging up to 42 days. Results:. The gentamicin, vancomycin, amikacin and ceftriaxone beads all inhibited growth of the MRSA on the TSB and agar plates, both before and after gas sterilisation. All four antibiotics continued to show similar zones of inhibition after 42 days of storage, with slight fluctuations from week to week. Conclusion:. The four antibiotic beads manufactured using limited resources and in the austere environment were all effective in inhibiting bacterial growth. The growth of MRSA was inhibited by the antibiotic beads. Gas sterilisation or storage at room temperature for up to 42 days did not adversely deteriorate the efficacy of the beads. The results show significant promise to produce beads with locally obtainable ingredients in an austere environment and improve cost effectiveness by storing them in a sterilised condition

Aims

To clarify the effectiveness of the induced membrane technique (IMT) using beta-tricalcium phosphate (β-TCP) for reconstruction of segmental bone defects by evaluating clinical and radiological outcomes, and the effect of defect size and operated site on surgical outcomes.

Background. Previous data from our institution show that more than half of all prosthetic joint infections are due to S. aureus. A significant proportion of these bacteria may have an endogenous source. Detecting and treating asymptomatic S. aureus nasal carriers preoperatively has been shown to reduce the risk of infection. Material and Methods. This is an ongoing prospective study that started in March/2009 and involves primary total knee or hip arthroplasties candidates. So far preoperative nasal swab cultures were performed in 211(61%) out of 347 patients operated until April/2010. Carriers are identified and randomly chosen for preoperative treatment consisting of nasal mupirocin twice a day and daily cloro-hexidine baths in the 5 days that precede surgery. Antibiotic prophylaxis is cefazolin 24hours adding a single vancomycin dose in MRSA carriers. Results. Around 30% (64/211) of patients presented Saureus nasal carriage and 6 of them (9.4%) were methicilin-resistant. Infection rate was lower in the non-carriers: 1.36% (2/147). The group of 33 untreated carriers so far has the higher prevalence of infection (6.06%; Odds ratio=4.677; p=0.098). In the 31 treated carriers there was only one infection to date (3.23%; Odds ratio=2.371; p=0.463). The 136 patients control group in which no preoperative nasal culture was made registered 4 infections (2.94%; Odds ratio=2.197; p=0.356). Five out of the nine infections involved S. aureus. We further isolated 3 S. epidermidis, 1 enterococcus and 2 gram-negatives. Discussion. It seems that two S. aureus infections were due to endogenous contamination as the infecting bacteria possesses the exact same phenotype as the colonizing preoperative one (one untreated and one treated carrier). In other two S. aureus cases the seeding appears exogenous (a preoperative negative culture and a infecting bacteria different than the preoperative screening). One infection was registered in a non-studied patient. Accordingly, exogenous contamination seems responsible for at least 6 out of 9 infections. Conclusion. These preliminary results suggest that S. aureus colonization may be an endogenous risk factor for prosthetic joint infection that can be influenced. However exogenous contamination is still a major risk factor in our institution

Objective. Ankle fractures are frequent and seem to be easy to handle in most cases. Of course, also these easy fractures can cause infections that must be carefully managed. What risk factors do we find? What options do we have in treating these complications? What are the consequences and what will the result for the patient be like, compared to non-infected cases?. In a retrospective study we included 82 patients treated with an osteosynthesis in ankle fractures (AO 44 B or C fractures). Average age was 52.4 years (range 20–84 years, median 51.0). Results. In 9 (10.9%) patients there were septic complications. Concerning risk factors, we found 4 (44.4%) patients with nicotine abuse, 2 (22.2%) with additional alcohol abuse. Average stay in hospital was 39.6 days (range 9–95 days). In 4 (44.4%) cases local infection was treated with antibiotics and rest alone. 5 (55.5%) of the patients had additional operations due to infection, in average 5.4 per patient (range 1–10). Early implant removal was done in 3 (33.3%) cases, in average after 3 months. We found 2 (22.2%) infections due to Staphylococcus aureus, 1 (11.1%) due to MRSA and one infection with MRSA and Proteus mirabilis. In one case vacuum dressing had been applied for 44 days. In another case infection could only be healed with an intramedullary vancomycin augmented spacer and finally a screw arthodesis of the ankle, this was a patient with proven arteriosclerosis of the lower extremities. All other fractures finally showed bony healing in xrays. No plastic surgery (e.g. flaps) was needed to close a wound definitely. In follow up (in average after 33 months, range 17–42), the average AOFAS of these patients was 76.5 (range 35–100, median 81.5), compared to an average AOFAS of 89.4 (range 35–100, median 98.0) of all patients. No patient developed a septic syndrom, no ICU stay occurred because of the infection. Conclusions. In spite of most cases of ankle fractures having good outcomes without complications, once infected an ankle osteosynthesis can be a serious problem for both surgeon and patient. Consequent surgical therapy at the right time including early hardware removal, spacers or vacuum dressing if necessary as well as an antibiotic regime addressing problematic pathogens like MRSA are needed to control infections. Problems remaining are functional outcome and wound closure in this sensitive area. Plastic surgery might be needed

Aims. Infections of bone usually require multiple surgery and prolonged periods of treatment. One reason for problems is found in the presence of stationary phase bacteria embedded in biofilms that show increased resistance against conventional antibiotic therapy (up to 1000x MIC). Biofilms adhere to surfaces of avital material making radical debridement a prerequisite for cure. Osseous defects are common in such conditions and need to be addressed. To avoid re-infection high local antbiotic concentrations are necessary. Allograft bone may be impregnated with high loads of antibiotics using a special incubation technique. The resulting antibiotic bone compound (ABC) provides high and long lasting concentrations at the site of infection and is likely to restore bone stock simultaneously. Based on this technology we have developed a new surgical technique. Methods. 42 patients (10–67yrs) with chronic osteitis were included into a prospective study using a standardized protocol. Infection was at the humerus (1x), femur (10x), tibia (29x) or femur+tibia (2x), respectively. Treatment consisted of removal of foreign material, radical sequestrectomy and soft-tissue debridement followed by pressurized lavage. Surfaces of sclerotic bone were trimmed down to vital areas. The remaining osseous defects were filled with ABC, using an impaction technique resulting in complete dead space management. The allograft was impregnated with vancomycin, in cases with mixed pathogens combinations with tobramycin were used. Internal fixation was performed the same time whenever applicable. Sites were drained and closed immediately; rehabilitation did not differ from uninfected procedures. Results. 1 patient died shortly after surgery from cardiac failure. 41 could be followed for a minimum of 2 and a maximum of 6years (mean 3,1years). In 2 patients wound healing was unsatisfactory requiring additional coverage with a muscle flap. 2 patients showed material failure after intramedullary nailing, requiring exchange of the implant. In those cases no sign of infection was present at the time of revision. There were 3 cases with recurrence of infection, all originating from foci not detected during the index operation and becoming apparent between 3 and 12 months after surgery. Two could successfully be revised using the same technique; one refused revision and shows continuing fistulation. Radiological incorporation of allografts appeared as after conventional bone grafting, union of pseudarthroses was achieved between 2 and 6 months after (re-) stabilization. 40 patients (95,2%) were fully weight bearing, painfree and without any sign of infection at the latest follow up. Conclusion. Using antibiotic impregnated allograft bone eradication of pathogens, grafting of defects, dead space management and insertion of osteosynthetic material may be accomplished in a one stage procedure. Since the graft gradually is replaced by healthy own bone improved long term results may be expected as well as improved conditions in the case of another revision. The new technique provides for quick rehabilitation, improved results and markedly reduced costs of treatment in cases of bone infection

Aims

The purpose of this study was to: review the efficacy of the induced membrane technique (IMT), also known as the Masquelet technique; and investigate the relationship between patient factors and technique variations on the outcomes of the IMT.

Aims

The aims of this study were to establish whether composite fixation (rail-plate) decreases fixator time and related problems in the management of patients with infected nonunion of tibia with a segmental defect, without compromising the anatomical and functional outcomes achieved using the classical Ilizarov technique. We also wished to study the acceptability of this technique using patient-based objective criteria.

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.

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

This study describes the use of the Masquelet technique to treat segmental tibial bone loss in 12 patients.

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.

We compared the outcome of closed intramedullary nailing with minimally invasive plate osteosynthesis using a percutaneous locked compression plate in patients with a distal metaphyseal fracture in a prospective study.

A total of 85 patients were randomised to operative stabilisation either by a closed intramedullary nail (44) or by minimally invasive osteosynthesis with a compression plate (41). Pre-operative variables included the patients’ age and the side and pattern of the fracture. Peri-operative variables were the operating time and the radiation time. Postoperative variables were wound problems, the time to union of the fracture, the functional American Orthopaedic Foot and Ankle surgery score and removal of hardware.

We found no significant difference in the pre-operative variables or in the time to union in the two groups. However, the mean radiation time and operating time were significantly longer in the locked compression plate group (3.0 vs 2.12 minutes, p < 0.001, and 97.9 vs 81.2 minutes, p < 0.001, respectively). After one year, all the fractures had united. Patients who had intramedullary nailing had a higher mean pain score, but better function, alignment and total American Orthopaedic Foot and Ankle surgery scores, although the differences were not statistically significant (p = 0.234, p = 0.157, p = 0.897, p = 0.177 respectively). Three (6.8%) patients in the intramedullary nailing group and six (14.6%) in the locked compression plate group showed delayed wound healing, and 37 (84.1%) in the former group and 38 (92.7%) in the latter group expressed a wish to have the implant removed.

We conclude that both closed intramedullary nailing and a percutaneous locked compression plate can be used safely to treat Orthopaedic Trauma Association type-43A distal metaphyseal fractures of the tibia. However, closed intramedullary nailing has the advantage of a shorter operating and radiation time and easier removal of the implant. We therefore prefer closed intramedullary nailing for patients with these fractures.