Introduction and Objective

Management of bone loss associated with bone contamination or infection represents a double biological and clinical challenge frequent in traumatology. The advent of new biomaterials can allow a different approach in the treatment of bone gap. The purpose of this study was to evaluate the prophylactic and therapeutic effectiveness of addition of a new absorbable bone substitute (BS) eluting different antibiotics in reconstruction of bone defects after infections and fractures with soft tissue damage.

Antibiotic-laden bone cement is an important strategy of treatment for an established bone infection. It was aimed to find the safe antibiotic dose intervals of the antibiotic cements soaked in Phosphate Buffered Saline solution and to determine whether there was a difference in terms of mechanical strength between the prepared samples.

This study was done in our institute Microbiology and Metallurgy laboratories. All samples were prepared using manual mixing technique using 40 g radiopaque Biomet® Bone cement (Zimmer Biomet, Indiana, USA) under sterile conditions at 19 ± 2 ºC.

In this study, vancomycin (4 groups − 0.5, 2, 4, 6 g), teicoplanin (4 groups − 0.8, 1.2, 2, 2.4 g), daptomycin (4 groups − 1, 2, 2.5, 3 g), piperacillin-tazobactam (4 groups − 0.125, 0.5, 1, 2 g) and meropenem (4 groups − 0.5, 2, 4, 6 g) were measured in a assay balance and added to the cement powder. Antibiotic levels ranged from the lowest 0.625% to the highest 15%.

80×10×4 mm rectangle prism-shaped sample for mechanical measurements in accordance to ISO 5833 standart and 12×6×1 mm disc-shaped samples for microbiological assesments were used. Four sample for each antibiotic dose and control group was made. Prepared samples were evaluated macroscopically and faulty samples were excluded from the study. Prepared samples were kept in Phosphate Buffered Saline solution renewed every 24 hours at 37 ºC. At the end of 6 weeks, all samples were tested with Instron ® 3369 (Norwood Massachusetts, USA) four point bending test.

Staphylococcus aureus (ATCC 29213) strain was used for samples of antibiotics containing vancomycin, teicoplanin and daptomycin after the samples prepared for antibiotic release were maintained under sterile conditions and kept in Phosphate Buffered Saline solution as appropriate. For samples containing meropenem and piperacillin - tazobactam antibiotics, Pseudomonas aeruginosa (ATCC 27853) strain was used.

The addition of more than 5% antibiotics to the cement powder was significantly reduced mechanical strength in all groups(p <0.05) however the power of significance was changed depending on the type of antibiotic. In general, adding antibiotics with 2.5% and less for cement amount was not cause significant changes in mechanical measurements. There was a negative correlation between the increase in the amount of antibiotics mixed with cement and the durability of the cement (p: <0.001, r: −0.883 to 0.914).

In this study, especially the antibacterial effects of piperacillin-tazobactam, containing 0.25 gr and 0.5 gr antibiotic doses, were found to be low. There was no bacterial growth in all other groups for 21 days. Considering the mechanical properties of groups containing meropenem, vancomycin, daptomycin and teicoplanin, it was observed that all antibiotic cements remained above the limit value of 50 MPa in the bending test at concentrations containing 2.5% and less antibiotics. This was not achieved for the piperacillin-tazobactam group. The findings of the study showed that each antibiotic has different MPa values at different doses. Therefore, it could be concluded that not only the antibiotic dose but also the type oould change the mechanical properties. In the light of these findings, mixing more than 2.5% antibiotics in cement for the antibiotic types included in the study was ineffective in terms of antibacterial effect and mechanically reduces the durability of cement below the standard value of 50 MPa.

By modifying only the nanofeatures on material surfaces without changing surface chemistry, it is possible to increase tissue growth of any human tissue by controlling the endogenous adsorption of adhesive proteins onto the material surface. In addition, our group has shown that these same nanofeatures and nano-modifications can reduce bacterial growth without using antibiotics, which may further accelerate the growth of antibiotic resistant microbes. Inflammation can also be decreased through the use of nanomaterials. Finally, nanomedicine has been shown to stimulate the growth and differentiation of stem cells, which may someday be used to treat incurable disorders, such as neural damage. This strategy also accelerates FDA approval and commercialization efforts since new chemistries are not proposed, rather chemistries already approved by the FDA with altered nanoscale features. This invited talk will highlight some of the advancements and emphasize current ceramic nanomaterials approved by the FDA for human implantation. It will also emphasize the future of nanomaterials in medicine, such as their use in personalized medicine as internal sensors to detect and fight alterations in health.

Introduction

Perioperative antibiotic prophylaxis use in modern orthopaedic procedures is well established. Studies have shown significant reduction in risk of post-operative infections. However, as effectiveness of these antibiotics is dependent on achieving high serum and tissue concentrations that exceed the minimum inhibitory concentrations of infective organisms for operation duration, the timing of prophylaxis is crucial. Although, optimal timing for administering prophylaxis varies in the literature, 30 to 60 minutes prior to skin incision or inflation of tourniquet is considered best standards.

Thermostability is a key property in determining the suitability of local delivery of antibiotics in the treatment of orthopaedic infections. Herein, we aimed to assess the thermal stability and antibacterial activity of ciprofloxacin, ceftriaxone, gentamycine and vancomycine in high temperature conditions. Using a standardized E-test method, minimally inhibited concentration of each antibiotic substance against Staphylococcus aureus cultures were determined. The solutions of antimicrobial drugs ciprofloxacin 2 mg/ml, ceftriaxone 200 mg/ml, gentamycine 40 mg/ml and vancomycine 200 mg/ml were diluted twofold in deionised water. Acquired solutions were divided into three aliquots. The first aliquot was held at 40°C for 30 min in a waterbath, the second and the third aliquots were exposed to 80 and 100°C for 30 min in hot-air sterilizer, respectively. The treated solutions were tested for residual activity against S. aureus using a standardized disk diffusion method. Mediums with untreated antibiotic solutions and S. aureus were used as control. Plates were incubated at 37°C, at which time zones of inhibition (ZoI) were measured to the nearest whole millimeter for 14 days. The investigation indicated that the temperature elevation impacted considerably on antimicrobial activity and antibiotic stability overall. The in vitro temperature-response curves showed that ZoI diameter decreases logarithmically with elevated temperatures. Gentamicin was the only drug that was found to be affected to some extent. Results from the study provides a valuable dataset for orthopaedic surgeons considering local application of antibiotics and methods of antibiotic impregnation.

We describe a case series using calcium sulphate bio composite with antibiotics (Cerament/Stimulan) in treating infected metalwork in the lower limb.

Eight patients aged 22–74 (7 males, 1 female) presented with clinical evidence of infected limb metal work from previous orthopaedic surgery. Metal work removal with application of either cerement in 5 cases (10–20ml including 175mg–350mg gentamycin) or stimulan in 3 cases (10–20ml including either 1g vancomycin or clindamycin 1.2g or 100mg tigecycline) into the site was performed. Supplemental systemic antibiotic therapy (oral/intravenous) was instituted based on intraoperative tissue culture and sensitivity.

Four patients had infected ankle metalwork, 2 patients infected distal tibial metalwork and 2 had infected external fixators. Metal work was removed in all cases. The mean pre operative CRP was 15.8mg/l (range 1–56mg/l). The mean postoperative CRP at 1 month was 20.5mg/l (range 2–98mg/l). The mean pre op WCC was 7.9×10⁹(range 4.7–10.5 ×10⁹). Mean post op WCC at 1 month was 7.1×10⁹(range 5.0–9.2×10⁹). The organisms cultured included enterobacter, staphylococcus aureus, staphylococcus epidermidis, staphylococcus cohnii, stenotrophomonas, acinetobacter, group B streptococcus, enterococcus and escherichia coli. No additional procedures were required in any case. All surgical wounds went on to heal uneventfully. Infection control and union was achieved both clinically and radiologically in all cases.

Our results support the use of a calcium sulphate bio composite with antibiotic as an adjuvant for effective local infection control in cases with implant related bone sepsis. The technique is well tolerated with no systemic or local side effects. We believe that implant removal, debridement and local antibiotic delivery can minimise the need for prolonged systemic antibiotic therapy in such cases.

Introduction

Guidelines from the North American Spine Society (2009 and 2013) are the best evidence-based instructions on venous thromboembolism (VTE) and antibiotic prophylaxis in spinal surgery. NICE guidelines exist for VTE prophylaxis but do not specifically address spinal surgery. In addition, the ruling of the UK Supreme Court in 2015 resulted in new guidance on consent being published by the Royal College of Surgeons of England (RCSEng). This study assesses our compliance in antibiotic, VTE prophylaxis and consent in spinal surgery against both US and UK standards.

The treatment of chronic osteomyelitis requires both appropriate surgical and antibiotic management. Prolonged intravenous antibiotic therapy followed by oral therapy is widely adopted. Despite this, the long-term recurrence rate is around 20% to 30%.

The aim of this cohort study was to examine the effectiveness of surgical marginal resection in combination with local application of antibiotics (Collatamp G - gentamicin in a collagen fleece). Post-operatively this was followed by a short course of intravenous antibiotics, then oral antibiotics, to 6 weeks in total.

A cohort of 50 patients from a 10-year period, 2000 to 2010, with chronic osteomyelitis was identified. Most were male (n= 35, 70%) and the average age is 40.9 years (SD 15.9). The mean follow-up duration was 3.2 years (SD 1.8). The average length of admission was 9.8 days (SD 11.4). 6 patients (12%) suffered recurrence of infection requiring further treatment. We used the Cierny and Mader classification to further stratify the patients. ‘A’ hosts had a shorter duration of admission (7.1 days) than ‘B’ hosts (12.3 days). There was no significant difference between recurrence rates of ‘A’ and ‘B’ hosts. Where available, we found pre-operative C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels had no correlation with disease recurrence. Disease-free probability for this cohort compared favourably with a cohort treated with prolonged systemic and oral antibiotics (Simpson and colleagues, JBJS Br 2001).

We believe local administration of gentamicin in a collagen fleece is a useful component in the management of chronic osteomyelitis.

Prophylactic antibiotics administered prior to joint arthroplasty have become standard practice. Due to concern over the risk that 2nd generation cephalosporins posed to the elderly, as regards clostridium difficile associated infections the antimicrobial management team in our unit changed the protocol for prophylactic antibiotics. As of 1st September 2009, flucloxacillin and gentamicin were preferred over cefuroxime as the first choice of prophylactic antibiotic. However, it was noted that postoperatively patients were experiencing a decrease in renal function.

One hundred patients who underwent a total hip replacement following the policy change were randomly selected from the departmental joint arthroplasty database. This group was age and sex matched to 100 patients undergoing their surgery prior to the change. Data was collected on renal function, length of stay, antibiotic and age. Any change in renal function was categorised using the RIFLE criteria.

Exclusion secondary to variations from protocol or treatment for femoral neck fractures resulted in a total number of 156 patients with 78 in each arm. The average age for both groups was 64 years. Non-parametric analysis of preoperative and postoperative serum creatinine concentrations and Glomerular Filtration Rate (GFR) demonstrated a significant difference between the two groups, showing that GFR decreased (p=0.041) and serum creatinine concentration increased (p=0.037) in the cohort receiving gentamicin. Classing the impaired renal function as: risk, injury or failure (RIFLE criteria) demonstrated a statistically significant difference for any criterion positive (p=0.016) but no significant difference for the specific RIFLE groups (p=0.068).

Acknowledging the small numbers and potential confounders for renal impairment, this study was able to show a difference in renal function for patients receiving gentamicin over cefuroxime as prophylaxis for joint arthroplasty.

Summary

There is little knowledge in surgeons about the guidelines for prophylactic antibiotics in patients with prosthetic joints when undergoing a dental procedure. This study confirms this and there is need for robust and universal guidelines given the disastrous nature of prosthetic infection.

Summary Statement

Combination of antibiotics with N-acetylcisteine and sub-MIC concentration of erythromycin was evaluated in two collection and 16 clinical strains of staphylococci isolated from PJI. The results were strain-dependent, so it evidences the necessity of perform individual studies of biofilm susceptibility.

Purpose

Gustilo type III open fractures are associated with high infection rates in spite of instituting a standard of care (SOC) consisting of intravenous antibiotics, irrigation and debridement (I&D), and delayed wound closure. Locally-delivered antibiotic has been proven to assist in reducing infection in open fractures. The aims of this study are to determine the effectiveness and safety of a new implantable and biodegradable antibacterial product¹ in preventing bacterial infections and initiating bone growth in open fractures.

Staphylococcus aureus (SA), the predominant pathogen in human osteomyelitis, is known to persist by forming intracellular reservoirs, including in bone cells (Schwarz et al., 2019, Yang et al., 2018, Krauss et al., 2019, Gao et al., 2020, Bosse et al., 2005), promoting decreased antibiotic susceptibility. However, there are no evidence-based treatment guidelines for intracellular SA infections in osteomyelitis. We sought to address this by systematically reviewing the literature and, testing a selection of antibiotic treatments in a clinically relevant in vitro assay. We conducted a systematic review of the literature to determine the current evidence for the efficacy of antibiotics against intracellular SA infections relevant to osteomyelitis. For the antibiotics identified as potentially useful, we determined their minimal inhibitory concentration (MIC) against 11 clinical osteomyelitis SA- isolates. We selected those for further testing reported able to reach a higher concentration in the bone than the identified MIC against the majority of strains. Thus, rifampicin, oxacillin, linezolid, levofloxacin, oritavancin and doxycycline were tested in human SaOS-2-osteocyte infection models (Gunn et al., 2021) of acute (1d) or chronic (14d) infection to clear intracellular SA. Antibiotics were tested at 1x/4x/10x the MIC for the duration of 1d or 7d in each model. A systematic review found that osteoblasts and macrophages have mostly been used to test immediate short-term activity against intracellular SA, with a high variability in methodology. However, some extant evidence supports that rifampicin, oritravancin, linezolid, moxifloxacin and oxacillin may be effective intracellular treatments. While studies are ongoing, in vitro testing in a clinically relevant model suggests that rifampicin, oxacillin and doxycycline could be effectively used to treat osteomyelitic intracellular SA infections. Importantly, these have lower MICs against multiple clinical isolates than their respective clinically-achievable bone concentrations. The combined approach of a systematic review and disease-relevant in vitro screening will potentially inform as to the best approach for treating osteomyelitis where intracellular SA infection is confirmed or suspected

Surgical microfracture is considered a first line treatment for talar osteochondral defects. Pain reduction, functional improvement and patient satisfaction are described to be 61–86% in both primary and secondary osteochondral defects. However, limited research is available whether improvement of the surgical technique is possible. We do know that the current rigid awls and drills limit the access to all locations in human joints and increase the risk of heat necrosis of bone. Application of a flexible water jet instrument to drill the microfracture holes can improve the reachability of the defect without inducing thermal damage. The aim of this study is to determine whether water jet drilling is a safe alternative compared to conventional microfracture awls by studying potential side effects and perioperative complications, as well as the quality of cartilage repair tissue in a caprine model. 6 mm diameter talar chondral defects were created bilaterally in 6 goats (12 samples). One defect in each goat was treated with microfracture holes created with conventional awls. The contralateral defect was treated with holes created with 5 second water jet bursts at a pressure of 50 MPa. The pressure was generated with a custom-made setup using an air compressor connected to a 300 litre accumulator that powered an air driven high-pressure pump (P160 Resato, Roden, The Netherlands, . www.resato.com. ). Postoperative complications were recorded. After 24 weeks, analyses were performed using the ICRS macroscopic score and the modified O'Driscoll histological score. Wilcoxon ranked sum tests were used to assess significant differences between the two instrument groups using each goat as its own control (p ≤ 0.05). One postoperative complication was signs of a prolonged wound healing with swelling and reluctance to weight bearing starting two days after surgery on the water jet side. Antibiotics were administered which resolved the symptoms. The median total ICRS score for the tali treated with water jets was 9,5 (range: 6–12) and 9 (range 2–11) for Observer 1 and 2 respectively; and for the tali treated conventionally this was 9,5 (range 5–11) and 9 range (2–10). The median total Modified O'Driscoll score for the tali treated with water jets was 15 (range: 7–17) and 13 (range: 3–20) for Observer 1 and 2 respectively; and for the tali treated conventionally was 13 (range: 11–21) and 15 (range: 9–20). No differences were found in complication rate or repair tissue quality between the two techniques. The results suggest that water jet drilling can be a safe alternative for conventional microfracture treatment. Future research and development will include the design of an arthroscopic prototype of the water jet drill. The focus will be on stability in nozzle positioning and minimized sterile saline consumption to further the decrease the risk of soft tissue damage

Discitis in childhood is rare. It can be difficult to diagnose, particularly in the younger child, often leading to a delay in initiation of appropriate treatment. It is not known whether it represents an infective or an inflammatory process. Our aim was to review all cases treated at a regional children's hospital since the introduction of the departmental database. A retrospective review (64,058 cases), for the period 1990-2008 was performed. 12 cases were identified (3 male/9 female), with a biphasic age distribution; eight [mean 22 months old (12-32)] and four [mean 12 years old (11-13)]. Mean time to diagnosis from onset was 22 days, (5-49). Symptoms varied with age, no one less than 28 months complained of back pain, while all over 28 months did, to a varying degree. All the younger children presented primarily with a gait abnormality. 92% (11/12) were apyrexial on admission. WBC and CRP were normal in 83% (10/12). Venous blood cultures were negative in 89% (8/9). Only ESR was mildly raised, mean 30 (10-65). Radiographs showed loss of intervertebral disc height in 91% (10/11), earliest by 10 days following onset symptoms, mean 28 days. A technetium bone scan was performed in 42% (5/12) and an MRI of the lumbar spine, in 58% (7/12). All were positive for discitis. All occurred in the lumbar spine, 50% at L3/4. Antibiotics were used in 11/12 (92%), flucloxacillin alone in the majority 9/11. One had non-steroidal medication alone. No form of brace was used. Mean follow-up was 13.3 months (2-36). In all, symptoms had resolved by mean 6.5 weeks (2-12). No recurrence was noted. The common features of childhood discitis are presented; knowledge of these may aid the physician to come to a more rapid diagnosis of this uncommon paediatric condition

Objectives

Thermal stability is a key property in determining the suitability of an antibiotic agent for local application in the treatment of orthopaedic infections. Despite the fact that long-term therapy is a stated goal of novel local delivery carriers, data describing thermal stability over a long period are scarce, and studies that avoid interference from specific carrier materials are absent from the orthopaedic literature.

Objectives

To review the current best surgical practice and detail a multi-disciplinary approach that could further reduce joint replacement infection.

Short intense electrical pulses transiently increase the permeability of the cell membrane, an effect known as electroporation. This can be combined with antiblastic drugs for ablation of tumours of the skin and subcutaneous tissue. The aim of this study was to test the efficacy of electroporation when applied to bone and to understand whether the presence of mineralised trabeculae would affect the capability of the electric field to porate the membrane of bone cells.

Different levels of electrical field were applied to the femoral bone of rabbits. The field distribution and modelling were simulated by computer. Specimens of bone from treated and control rabbits were obtained for histology, histomorphometry and biomechanical testing.

After seven days, the area of ablation had increased in line with the number of pulses and/or with the amplitude of the electrical field applied. The osteogenic activity in the ablated area had recovered by 30 days. Biomechanical testing showed structural integrity of the bone at both times.

Electroporation using the appropriate combination of voltage and pulses induced ablation of bone cells without affecting the recovery of osteogenic activity. It can be an effective treatment in bone and when used in combination with drugs, an option for the treatment of metastases.

Ciprofloxacin hydrochloride-loaded microspheres were prepared by a spray-drying method using pectin and chitosan. The effects of different polymers and drug ratios were investigated.

The most appropriate carriers were selected by in vitro testing. A rat methicillin-resistant Staphylococcus aureus osteomyelitis model was used to evaluate the effects of the loaded microspheres.

The drug was released rapidly from the pectin carrier but this was more sustained in the chitosan formulation.

Chitosan microspheres loaded with ciprofloxacin hydrochloride were more effective for the treatment of osteomyelitis than equivalent intramuscular antibiotics.

We investigated the effect of stimulation with a pulsed electromagnetic field on the osseointegration of hydroxyapatite in cortical bone in rabbits. Implants were inserted into femoral cortical bone and were stimulated for six hours per day for three weeks.

Electromagnetic stimulation improved osseointegration of hydroxyapatite compared with animals which did not receive this treatment in terms of direct contact with the bone, the maturity of the bone and mechanical fixation. The highest values of maximum push-out force (F_max) and ultimate shear strength (σ_u) were observed in the treated group and differed significantly from those of the control group at three weeks (F_max; p < 0.0001; σ_u, p < 0.0005).