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

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

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

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

Between October 2001 and February 2002, 324 healthcare workers were screened for methicillin-resistant Staphylococcus aureus (MRSA) by nose and throat swabs. A positive finding led to activation of a standardised control programme for the affected person who was immediately excluded from work. Family members of those who were MRSA-positive were offered screening free of charge. An eradication programme was carried out in the permanent carriers. MRSA was found in 17 (5.3%) healthcare workers, 11 of whom proved to be permanent carriers, and six temporarily colonised. Three children of a positive healthcare worker showed nasopharyngeal MRSA, the acquisition of which occurred within the hospital. The standardised eradication programme for carriers was successful in most cases but failed in two individuals, whereupon systemic antibiotics were used successfully. The decolonised carriers, observed for more than one year, remained MRSA negative. Isolation precautions in hospitals do not always prevent hospital staff and their families from acquiring MRSA. The identification of affected employees is difficult because in most cases only asymptomatic colonisation occurs. Screening and eradication can be complicated and costly, and for the affected employees the occupational consequences can be far-reaching as they have no guaranteed legal protection

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

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.

Background. Both from experimental studies and the large arthroplasty registries there is evidence that bacteria are more often involved in implant loosening then is currently reported. To further elucidate this potential problem, the current study investigated the hypothesis that many total hip arthroplasty revisions, classified as aseptic, are in fact low-grade infections missed with routine diagnostics. Methods. In 7 Dutch hospitals, 176 patients with the preoperative diagnosis of aseptic loosening of their total hip arthroplasty were enrolled. From each patient, the preoperative history was obtained. During surgery, between 14 and 20 tissue samples were obtained for routine culture, pathology analysis and broad range 16S rRNA PCR with reverse line blot hybridization (PCR-RLB). Samples were taken from the (neo-) capsule and acetabular and femoral interface tissue. Cultures were performed locally according to similar protocols. One specialized pathologist, blinded for all other results, analyzed all pathology samples. The PCR-RLB analysis was performed centrally, using a technique previously validated for orthopedic use. Patients were classified as not infected, suspect for infection or infected, according to strict, predefined criteria. Each patient had a follow-up visit after 1 year. Results. Seven patients were classified as infected, of whom 4 were not identified by routine culture. In these patients, positive PCR-RLB results were supported by pathology analyses suspect for infection as well. An additional 15 patients were suspect for infection as well. The microorganisms identified were low virulent bacteria, like coagulase negative staphylococci and Proprionibacterium acnes, in most cases. Twenty of these 22 patients received a cemented prosthesis, fixated with antibiotic-loaded bone cement. All patients received prophylactic systemic antibiotics, after obtaining the tissue samples. Seven of the 22 patients reported complaints one year post-surgery, only one showing signs of early loosening. However, in none of the patients additional surgery was performed. Discussion. Although percentages were not as high as previously reported in literature, between 4 and 13 percent of patients with the preoperative diagnosis of aseptic loosening were infected. However, as thorough debridement was performed during surgery and prophylactic antibiotics were used, it did not have many clinical consequences, as most patients performed well at the 1-year follow-up. Whether it has implications for long-term implant survival remains to be seen

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.

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

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.

Most animal studies indicate that early irrigation and debridement reduce infection after an open fracture. Unfortunately, these studies often do not involve antibiotics. Clinical studies indicate that the timing of initial debridement does not affect the rate of infection but these studies are observational and fraught with confounding variables. The purpose of this study was to control these variables using an animal model incorporating systemic antibiotics and surgical treatment.

We used a rat femur model with a defect which was contaminated with Staphylococcus aureus and treated with a three-day course of systemic cefazolin (5 mg/kg 12-hourly) and debridement and irrigation, both of which were initiated independently at two, six and 24 hour time points. After 14 days the bone and hardware were harvested for separate microbiological analysis.

No animal that received antibiotics and surgery two hours after injury had detectable bacteria. When antibiotics were started at two hours, a delay in surgical treatment from two to six hours significantly increased the development of infection (p = 0.047). However, delaying surgery to 24 hours increase the rate of infection, but not significantly (p = 0.054). The timing of antibiotics had a more significant effect on the proportion of positive samples than earlier surgery. Delaying antibiotics to six or 24 hours had a profoundly detrimental effect on the infection rate regardless of the timing of surgery. These findings are consistent with the concept that bacteria progress from a vulnerable planktonic form to a treatment-resistant biofilm.

Our aim was to determine the effect of delay to surgery on the time to discharge, in-hospital death, the presence of major and minor medical complications and the incidence of pressure sores in patients with a fracture of the hip. All patients admitted to Vancouver General Hospital with this injury between 1998 and 2001 inclusive were identified from our trauma registry. A review of the case notes was performed to determine the delay in time from admission to surgery, age, gender, type of fracture and medical comorbidities. A time-to-event analysis was performed for length of stay. Additionally, a Cox proportional hazards model was used to determine the effect of delay to surgery on the length of stay while controlling for other pertinent confounding factors. Using logistical regression we determined the effect of delay to surgery on in-hospital death, medical complications and the presence of pressure sores, while controlling for confounding factors.

Delay to surgery (p = 0.0255), comorbidity (p < 0.0001), age (p < 0.0001) and type of fracture (p = 0.0004) were all significant in the Cox proportional hazards model for increased time to discharge. Delay to surgery was not a significant predictor of in-hospital mortality. However, a delay of more than 24 hours was a significant predictor of a minor medical complication (odds ratio (OR) 1.53, 95% confidence interval (CI) 1.05 to 2.22), while a delay of more than 48 hours was associated with an increased risk of a major medical complication (OR 2.21, 95% CI 1.01 to 4.34), a minor medical complication (OR 2.27, 95% CI 1.38 to 3.72) and of pressure sores (OR 2.29, 95% CI 1.19 to 4.40).

Patients with a fracture of the hip should have surgery early to lessen the time to acute-care hospital discharge and to minimise the risk of complications.

In this retrospective study we evaluated the method of acute shortening and distraction osteogenesis for the treatment of tibial nonunion with bone loss in 17 patients with a mean age of 36 years (10 to 58). The mean bone loss was 5.6 cm (3 to 10). In infected cases, we performed the treatment in two stages. The mean follow-up time was 43.5 months (24 to 96). The mean time in external fixation was 8.0 months (4 to 13) and the mean external fixator index was 1.4 months/cm (1.1 to 1.8). There was no recurrence of infection. The bone evaluation results were excellent in 16 patients and good in one, while functional results were excellent in 15 and good in two. The complication rate was 1.2 per patient.

We conclude that acute shortening and distraction osteogenesis is a safe, reliable and successful method for the treatment of tibial nonunion with bone loss, with a shorter period of treatment and lower rate of complication.