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

Cephalasporin antibiotics have been commonly used for prophylaxis against surgical site infection. To prevent Clostridium difficile, the preferential use of agents such as flucloxacillin and gentamicin has been recommended. The aim of this study was to investigate the bone penetration of these antibiotics during hip and knee arthroplasty, and their efficacy against Staphylococcus aureus and S. epidermidis. Bone samples were collected from 21 patients undergoing total knee arthroplasty (TKA) and 18 patients undergoing total hip replacement (THA). The concentration of both antibiotics was analysed using high performance liquid chromatography. Penetration was expressed as a percentage of venous blood concentration. The efficacy against common infecting organisms was measured using the epidemiological cut-off value for resistance (ECOFF). The bone penetration of gentamicin was higher than flucloxacillin. The concentration of both antibiotics was higher in the acetabulum than the femoral head or neck (p=0.007 flucloxacillin; p=0.021 gentamicin). Flucloxacillin concentrations were effective against S. aureus and S. epidermis in all THAs and 20 (95%) TKAs. Gentamicin concentrations were effective against S.epidermis in all bone samples. Gentamicin was effective against S. aureus in 11 (89%) femoral samples. Effective concentrations of gentamicin against S. aureus were only achieved in 4 (19%) femoral and 6 (29%) tibial samples in TKA. Flucloxacillin and gentamicin was found to effectively penetrate bone during arthroplasty. Gentamicin was effective against S. epidermidis in both THA and TKA, while it was found to be less effective against S. aureus during TKA. Bone penetration of both antibiotics was less in TKA than THA

Staphylococcus aureus is responsible for 60–70% infections of surgical implants and prostheses in Orthopaedic surgery, costing the NHS £120–200 million per annum. Its ability to develop resistance or tolerance to a diverse range of antimicrobial compounds, threatens to halt routine elective implant surgery. One strategy to overcome this problem is to look beyond traditional antimicrobial drug therapies and investigate other treatment modalities. Biophysical modalities, such as ultrasound, are poorly explored, but preliminary work has shown potential benefit, especially when combined with existing antibiotics. Using a methicillin-sensitive S. aureus reference strain and the dissolvable bead assay, biofilms were challenged by a low-intensity ultrasound (1.5MHz, 30mW/cm2, pulse duration 200µs/1KHz) for 20 minutes and gentamicin. The outcome measures were colony-forming units/mL (CFU/mL) and the minimum biofilm eradication concentration (MBEC) of gentamicin. The mean number of S. aureus within control biofilms was 1.04 × 109 CFU/mL. There was no clinically or statistically significant (p=0.531) reduction in viable S. aureus following ultrasound therapy alone. The MBEC of gentamicin for this S. aureus strain was 256 mg/L. The MBEC of gentamicin with the addition of ultrasound was 64mg/L. Further studies confirmed that the mechanism of action was due to incomplete disruption of the extracellular matrix with subsequent metabolic stimulation of the dormant biofilm-associated bacteria due to increased nutrient availability and oxygen tension. Low intensity pulsed ultrasound was associated with a 4-fold reduction in the effective biofilm eradication concentration of gentamicin; bringing the MBEC of gentamicin to within clinically achievable concentrations

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

SIGN guidelines advise the use of flucloxacillin and gentamicin instead of cefuroxime as antibiotic prophylaxis for elective hip and knee arthroplasty. It is our impression that this change in practice has been associated with an increased risk of acute kidney injury (AKI). During a twelve month period we examined the incidence of AKI sequentially in four groups of patients: cefuroxime prophylaxis (n = 46); high dose flucloxacillin (5-8g) with single shot gentamicin (n = 50); low dose flucloxacillin (1-4 g) with single shot gentamicin (n = 45); and finally cefuroxime again (n = 52). There were no statistically significant differences by chi-square tests for age, gender, operation (hip or knee), ASA, anaesthesia, baseline serum creatinine, hypertension, diabetes or pre-operative medication. The proportion of patients in each antibiotic group with any form of AKI by RIFLE criteria was: cefuroxime group 1 (9%), high dose flucloxacillin (52%), low dose flucloxacillin (22%), cefuroxime 2 (14%) (p < 0.0001 by chi-square test). Odds ratios (OR) for AKI derived from a multivariate logistic regression model and assigning an OR of 1 to cefuroxime group 1 was: high dose flucloxacillin 14.5 (95% CI, 4.2, 50.2); low dose flucloxacillin 3.0 (0.8-10.9) and cefuroxime group 2 1.9 (0.5, 7.4). Three patients in the high dose flucloxacillin group required temporary haemodialysis. We have shown a strong association between high dose prophylactic flucloxacillin and subsequent development of AKI. We have no reason to believe that this was confounded by any of the co-variates we measured

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.

Aims

To compare the cost-effectiveness of high-dose, dual-antibiotic cement versus single-antibiotic cement for the treatment of displaced intracapsular hip fractures in older adults.

The cement used for hemiarthroplasties by the authors and many other surgeons in the UK is Palacos® (containing 0.5g Gentamicin). Similar cement, Copal® (containing 1g Gentamicin and 1g Clindamycin) has been used in revision arthroplasties. We aim to investigate the effect on SSI rates of doubling the gentamicin dose and adding a second antibiotic (clindamycin) to the bone cement in hip hemiarthroplasty. We randomised 848 consecutive patients undergoing cemented hip hemiarthroplasty for fractured NOF into two groups: Group I, 464 patients, received standard cement (Palacos®) and Group II, 384 patients, received high dose, double antibiotic-impregnated cement (Copal®). We calculated the SSI rate for each group at 30 days post-surgery. The patients, reviewers and statistician were blinded as to treatment group. The demographics and co-morbid conditions were statistically similar between the groups. The combined superficial and deep SSI rates were 5 % (20/394) and 1.7% (6/344) for groups I and II respectively (p=0.01). Group I had a deep infection rate 3.3 %(13/394) compared to 1.16% (4/344) in group II (p=0.082). Group I had a superficial infection rate 1.7 % (7/394) compared to 0.58% (2/344) in group II (p=0.1861). 33(4%) patients were lost to follow up, and 77 (9%) patients were deceased at the 30 day end point. Using high dose double antibiotic-impregnated cement rather than standard low dose antibiotic-impregnated cement significantly reduced the SSI rate (1.7% vs 5%; p=0.01) after hip hemiarthroplasty for fractured neck of femur in this prospective randomised controlled trial

Methicillin Resistant Staphylococcus Aureus (MRSA) screening has reduced rates of MRSA infection in primary total hip (THR) and total knee (TKR) replacements. There are reports of increasing methicillin resistance (MR) in Coagulase Negative Staphylococci (CNS) causing arthroplasty infections. We examined microbiological results of all 2-stage THR/TKR revisions in Tayside from 2001–2010. 72 revisions in 67 patients were included; 30 THRs and 42 TKRs. Mean ages at revision were 89 and 72 years respectively. Male: female ratio 1.4:1.2-year survivorship for all endpoints: 96% in THRs and 88% in TKRs. 5-year survival: 83% and 84% respectively. The most common organisms were SA (30%) and CNS (29%). Antibiotic resistance was more common amongst CNS. 72% of CNS were resistant to Methicillin versus 20% of SA. 80% of CNS were resistant to Gentamicin OR Methicillin versus 20% of SA. 32% (8/72 cases or 11% overall) of CNS were resistant to BOTH Gentamicin AND Methicillin, the primary arthroplasty antibiotic prophylaxis in our region, versus 4% of SA. Harris Hip Scores and Knee Society Scores were lower post primary, prior to symptoms of infection in patients who had MR organisms cultured compared with those who had methicillin sensitive organisms. One-year post revision both groups recovered to similar scores. Our data suggest MR-CNS cause significantly more arthroplasty infections than MRSA. Patients developing MR infections tend to have poorer post-primary knee and hip scores before symptoms of infection fully develop. 32% of CNS causing arthroplasty infections in our region are resistant to current routine primary antibiotic prophylaxis

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

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

Factors associated with high mortality rates in geriatric hip fracture patients are frequently unmodifiable. Time to surgery, however, might be a modifiable factor of interest to optimize clinical outcomes after hip fracture surgery. This study aims to determine the influence of postponement of surgery due to non-medical reasons on clinical outcomes in acute hip fracture surgery.

Aims

Patients receiving cemented hemiarthroplasties after hip fracture have a significant risk of deep surgical site infection (SSI). Standard UK practice to minimize the risk of SSI includes the use of antibiotic-loaded bone cement with no consensus regarding type, dose, or antibiotic content of the cement. This is the protocol for a randomized clinical trial to investigate the clinical and cost-effectiveness of high dose dual antibiotic-loaded cement in comparison to low dose single antibiotic-loaded cement in patients 60 years and over receiving a cemented hemiarthroplasty for an intracapsular hip fracture.

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

Deep surgical site infection (SSI) remains an unsolved problem after hip fracture. Debridement, antibiotic, and implant retention (DAIR) has become a mainstream treatment in elective periprosthetic joint infection; however, evidence for DAIR after infected hip hemiarthroplaty is limited.

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.

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

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

Surgical site infection can be a devastating complication of hemiarthroplasty of the hip, when performed in elderly patients with a displaced fracture of the femoral neck. It results in a prolonged stay in hospital, a poor outcome and increased costs. Many studies have identified risk and prognostic factors for deep infection. However, most have combined the rates of infection following total hip arthroplasty and internal fixation as well as hemiarthroplasty, despite the fact that they are different entities. The aim of this study was to clarify the risk and prognostic factors causing deep infection after hemiarthroplasty alone.