Aims

Periprosthetic hip-joint infection is a multifaceted and highly detrimental outcome for patients and clinicians. The incidence of prosthetic joint infection reported within two years of primary hip arthroplasty ranges from 0.8% to 2.1%. Costs of treatment are over five-times greater in people with periprosthetic hip joint infection than in those with no infection. Currently, there are no national evidence-based guidelines for treatment and management of this condition to guide clinical practice or to inform clinical study design. The aim of this study is to develop guidelines based on evidence from the six-year INFection and ORthopaedic Management (INFORM) research programme.

Introduction and Objective. The continued effectiveness of antibiotic loaded bone cements is threatened by antibiotic resistance. The common antiseptic, chlorhexidine (CHX), is a potential alternative to antibiotics in bone cements, but conventional salts are highly soluble, causing burst release and rapid decline to subinhibitory local CHX concentrations. Here, chlorhexidine triphosphate (CHX-TP), a low solubility CHX salt, is investigated as an alternative antimicrobial in PMMA bone cements. The aim was to assess duration of antimicrobial release and antimicrobial efficacy, along with handling, setting and mechanical properties of CHX-TP loaded cements, compared with an existing cement formulation containing gentamicin. Materials and Methods. Palacos R (Heraeus Medical, Newbury, UK) with 0, 1, 4, 7 and 12% CHX-TP (w/w) cements were prepared by combining solid CHX-TP with Palacos R components, and compared with Palacos R+G. All cements were prepared without vacuum and under ISO 5833:2002 conditions. Cements were tested under ISO 5833:2002 for compressive and bending properties, setting time, maximum temperature and doughing time. Antimicrobial release from the cements into deionised water was studied and antimicrobial efficacy of unaged and aged cements against Staphylococcus aureus (ATCC 29213) was assessed using a disc diffusion assay. Results. Compressive strength of CHX-TP loaded cements was not significantly different to Palacos R or Palacos R+G (p > 0.05, all exceeding ISO 5833:2002 minimum of 70 MPa). Mean bending strength was significantly lower with CHX-TP loading (p < 0.05) than bending strength of Palacos R and Palacos R+G, though all bending moduli exceeded the ISO 5833:2002 minimum (1800 MPa). All cements studied were within the ISO 5833:2002 limits for setting time (3 to 15 min), doughing time (≤ 5 min) and maximum temperature (90 . o. C). Mean doughing time for Palacos R, Palacos R+G and Palacos R + 12 % CHX-TP respectively: 52.5 s, 45 s and 45 s. Mean setting time and mean maximum temperature for Palacos R, Palacos R+G and Palacos R + 1, 4, 7 and 12% CHX-TP respectively: 11.00 min (73 . o. C), 11.25 min (72 . o. C), 12.25 min (66 . o. C), 10.50 min (70 . o. C), 10.00 min (70 . o. C), 10.75 min (62 . o. C). Sustained CHX release into deionised water was observed from all Palacos R + CHX-TP cements. Duration varied according to CHX-TP dosing and diminished over time, although to an extent that itself varied with dosing. 1 % CHX-TP ceased releasing CHX at 6.9 weeks; 4 % CHX-TP ceased at 67.7 weeks; 7 % and 12 % CHX-TP were ongoing at 75.5 weeks. Palacos R+G cements ceased releasing detectable levels of gentamicin after 14.4 weeks. Palacos R+G and Palacos R + CHX-TP cement discs showed efficacy against S. aureus (ATCC 29213) when applied as prepared (unaged) to S. aureus bacterial lawns in disc diffusion assays, with CHX-TP cements showing dose dependency. Zone of inhibition (ZOI) size was significantly reduced for Palacos R+G cements and Palacos R + 1% CHX-TP cements after 1 week and 6 weeks aging, compared to ZOI from unaged cements (p < 0.05). ZOI size produced by Palacos R + 4, 7, and 12 % CHX-TP cements did not decline significantly after 6 weeks aging (p > 0.05). Conclusions. CHX-TP can be incorporated into the Palacos R cement matrix up to 12% w/w without deterioration of compressive strength, bending modulus, doughing time, setting time or maximum temperature. Bending strength was significantly reduced at all CHX-TP loadings studied. Palacos R + 4, 7 and 12% CHX-TP cements provided sustained CHX release, exceeding the duration of gentamicin release from Palacos R+G, and showed sustained efficacy against S. Aureus after 6 weeks aging, which was not achieved by Palacos R+G cements

Orthopedic device-related bone infection is one of the most distressing complications of the surgical fixation of fractures. Despite best practice in medical and surgical interventions, the rate of infection remains stubbornly persistent, and current estimates indicate that treatment failure rates are also significant. As we approach the limit of the effectiveness of current anti-infective preventative and therapeutic strategies, novel approaches to infection management assume great importance. This presentation will describe our efforts to develop and test various hydrogels to serve as customized antibiotic delivery vehicles for infection prevention and treatment. Hydrogels offer solutions for many of the challenges faced by complex trauma wounds as they are not restricted spatially within a poorly defined surgical field, they often degrade rapidly with no compatibility issues, and releases 100% of the loaded antibiotic. The preliminary data set proving efficacy in preventing and treating infection in both rabbit and sheep studies will be described, including local antibiotic concentrations in the intramedullary canal over time, compared to that of the more conventional antibiotic loaded bone cement. These two technologies show potential for the prevention and treatment of infection in trauma patients, with a clear focus on optimized antibiotic delivery tailored for complex wounds

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. Methods. The WHiTE 8 Copal Or Palacos Antibiotic Loaded bone cement trial (WHiTE 8 COPAL) is a multicentre, multi-surgeon, parallel, two-arm, randomized clinical trial. The pragmatic study will be embedded in the World Hip Trauma Evaluation (WHiTE) (ISRCTN 63982700). Participants, including those that lack capacity, will be allocated on a 1:1 basis stratified by recruitment centre to either a low dose single antibiotic-loaded bone cement or a high dose dual antibiotic-loaded bone cement. The primary analysis will compare the differences in deep SSI rate as defined by the Centers for Disease Control and Prevention within 90 days of surgery via medical record review and patient self-reported questionnaires. Secondary outcomes include UK Core Outcome Set for hip fractures, complications, rate of antibiotic prescription, resistance patterns of deep SSI, and resource use (more specifically, cost-effectiveness) up to four months post-randomization. A minimum of 4,920 patients will be recruited to obtain 90% power to detect an absolute difference of 1.5% in the rate of deep SSI at 90 days for the expected 3% deep SSI rate in the control group. Conclusion. The results of this trial will provide evidence regarding clinical and cost-effectiveness between low dose single and high dose dual antibiotic-loaded bone cement, which will inform policy and practice guidelines such as the National Institute for Health and Care Excellence guidance on management of hip fractures. Cite this article: Bone Jt Open 2021;2(2):72–78

Aims

The aim of this study was to assess the effects of transferring patients to a specialized arthroplasty centre between the first and second stages (interstage) of prosthetic joint infection (PJI) of the knee.

Background. Antibiotic loaded bone cement (ALBC) is commonly used in cemented total hip arthroplasty (THA) in an attempt to reduce the risk of prosthetic joint infection (PJI). However, its role versus plain cement remains controversial due to the potential risk of developing resistant organisms and potential excess costs incurred from its usage. We investigated the relationship of ALBC and plain cement in affecting outcome of revision surgery after primary THA. Methodology. We conducted a retrospective study of data collected from National Joint Registry for England and Wales, Northern Ireland and the Isle of Man between 1. st. September 2005 until 31. st. August 2017. A logistic regression analysis model was used to investigate the association between ALBC versus plain cement and the odds ratio (OR) for revision, adjusting for age, ASA grade, bearing surfaces, head size and cup and stem fixation. Indications for revision recorded in NJR were considered in separate models. Results. We identified 418,925 THAs where bone cements were used (22,037 plain cement; 396,888 ALBC). After adjusting for confounding factors, the risk of revision for infection was lower with ALBC (OR 0.77, 95% CI 0.62–0.95). There was also lower risk of revision for aseptic loosening of stem (OR 0.53, 95% CI 0.39–0.72), aseptic loosening of socket (OR 0.46, 95% CI 0.37– 0.58). When breaking down hips into fully cemented or hybrid fixation, the protective effect of ALBC against infection was only apparent in fully cemented (OR 0.65, 95% CI 0.48–0.87) when compared against hybrid fixation (OR 0.90, 95% CI 0.66–1.23). Discussion. Within the limits of registry analysis, this study has demonstrated an association between the use of ALBC and lower rates of revision for infection and aseptic loosening. Conclusion. This finding supports the current use of ABLC in cemented THAs

Background. Tigecycline, the first member of glycylcycline family, has effective antimicrobial activity against resistant and implant associated infectious organisms. The objectives of this study are to assess the compressive and tensile mechanical strength characteristics of tigecycline loaded bone cement and to compare them with vancomycin and daptomycin loaded bone cements which are used in prosthetic joint infections with resistant microorganisms. Methods. A control group without antibiotics and three antibiotic loaded bone cement groups with varying concentrations (1g, 2g and 3g vancomycin, 0.5g, 1g and 1.5g daptomycin and 50mg, 100mg and 150mg tigecycline) were prepared and tested according to ASTM F451 and ISO 5833 standards. Statistical analysis of the obtained data done by using LSD (least significant difference) and Bonferroni corrected Mann Whitney tests. Results. Both compression and tension tests showed that all determined antibiotic concentrations resulted in significant decrease when compared to the control group. Despite heterogenous statistical results, it was seen that the mechanical strength of tigecycline loaded bone cement was not significantly lower (even higher in some comparisons) when compared to vancomycin and daptomycin loaded bone cements. Conclusion. When used at defined concentrations, tigecycline loaded bone cement does not have mechanical disadvantage compared to vancomycin and daptomycin loaded bone cements. Thus, it should be kept in mind as an option in appropriate clinical situations

Objectives. Investigate the incorporation of an antibiotic in bone cement using liposomes (a drug delivery system) with the potential to promote osseointegration at the bone cement interface whilst maintaining antibiotic elution, anti-microbiological efficacy and cement mechanical properties. Prosthetic joint infection and aseptic loosening are associated with significant morbidity. Antibiotic loaded bone cement is commonly used and successfully reduces infection rates; however, there is increasing resistance to the commonly used gentamicin. Previous studies have shown gentamicin incorporated into bone cement using liposomes can maintain the cement's mechanical properties and improve antibiotic elution. The phospholipid phosphatidyl-l-serine has been postulated to encourage surface osteoblast attachment and in a liposome could improve osseointegration, thereby reducing aseptic loosening. Preliminary clinical isolate testing showed excellent antimicrobial action with amoxicillin therefore the study aims were to test amoxicillin incorporated into bone cement using liposomes containing phosphatidyl-l-serine in terms of antibiotic elution, microbiological profile and mechanical properties. Methods. Amoxicillin was encapsulated within 100nm liposomes containing phosphatidyl-L-serine and added to PMMA bone cement (Palacos R (Heraeus Medical, Newbury, UK)). Mechanical testing was performed according to Acrylic Cement standards (ISO BS 5833:2002). Elution testing was carried out along with microbiological testing utilising clinical isolates. Results. Liposomal encapsulated amoxicillin PMMA bone cement exceeded minimum ISO BS 5833:2002 standards, had better elution at 12.9% when compared with plain amoxicillin (p=0.036 at 48 hours) or commercial gentamicin cement (Palacos R+G, Heraeus Medical, Newbury, UK – previous studies showed 6% elution over the same time period). Amoxicillin showed superior antimicrobial action when compared with gentamicin of the same concentration. However, liposomal encapsulated amoxicillin in solution and liposomal encapsulated amoxicillin in PMMA were both less effective than free amoxicillin in bacterial growth inhibition. The liposomal amoxicillin also seemed to decrease the cement setting time. Conclusions. Phosphatidyl-l-serine containing liposomes maintained the cement's mechanical properties and seemed to have better antibiotic elution, however, had less effective antibacterial action than plain amoxicillin. This difference in antibacterial action requires further investigation along with investigation of osteoblast attachment to phosphatidyl-l-serine containing liposomes within cement. Plain amoxicillin, for those not penicillin allergic, seems to be a credible alternative to gentamicin for incorporation in PMMA bone cement. It has shown superior antibacterial action, which may improve infection rates, whilst maintaining the cement's mechanical properties

Total joint replacement (TJR), such as hip and knee replacement, is commonly used for the treatment of end stage arthritis. The use of Poly (methylmethacrylate) bone cement is a gold standard in such replacement, where it fixes the implant in place and transfer stresses between bone and implant, and frequently used for local delivery of drugs such as antibiotics. The use of antibiotic loaded bone cement is considered a well-established standard in the treatment and prophylaxis of Prosthetic joint infections (PJI). PJIs is a serious problem that decreases success rate of surgery and can be life threatening to patients, where the incidence can reach up 2% in total and hip replacements and up to 40% for revision surgery. Currently used antibiotic loaded bone cements have many limitations, including burst release of < 10% of antibiotic added. This burst release falls rapidly below inhibitory level within few days, which leads to selection of resistant antimicrobial strains and does not provide prophylaxis from early and delayed stage infection. This study aims to provide a controlled release for gentamicin when loaded on Silica nanoparticles (NP) using layer-by-layer technique (LbL) to provide prophylaxis and treatment from postsurgical infections. The gentamicin loaded NPs were incorporated into PMMA bone cement and the new nanocomposite is characterized for gentamicin release, antimicrobial and mechanical properties. Our results showed that the nanocomposite gentamicin release continued for 30 days at concentration 3 times higher than the commercial formulation containing the same amount of gentamicin, where burst release for few days were observed. Moreover, the nanocomposite showed superior antimicrobial inhibition for bacterial growth and good cytocompatibility without adversely affecting the cement compressive strength, bending and fracture toughness properties

Infection prevention in shoulder arthroplasty is an evolving challenge as further understanding of the pathogens becomes available. Infection rates for reverse TSA is higher than anatomic TSA. Standard decolonization protocols from our hip and knee colleagues has decreased the acute post-operative infection risk to less than 1%. By identifying at risk populations anti-MRSA precautions including intranasal antibiotics and anti-bacterial soaps for pre-surgical skin preparation have reduced the incidence of staphylococcus infections. The emerging understanding of propionibacterium acnes (P. acnes) as a primary pathogen in late shoulder periprosthetic joint infection (PJI) has led to new recommendations including pre-operative skin cleansing with 5% benzoyl peroxide to reduce infection risk. Pre-operative IV antibiotic is recommended and chlorhexidine skin prep for surgery. In the operating room, the concern is the surgeon's exposure to skin and sebaceous glands where P. acnes is prevalent. After skin incision the surgeon should use a new blade for deep incision. Application of vancomycin powder to the subcutaneous tissue may be beneficial after incision to treat potential contamination from the incision through skin. Glove change prior to handling implants and thorough irrigation before implantation is prudent. The role of antibiotic loaded bone cement for infection prevention remains unproven. Topical vancomycin powder at closure is a low cost option and has shown benefit in spine surgery but efficacy is unproven in the shoulder. Silver impregnated wound dressings may also prevent infection and are a convenient option for patient care with regards to bathing. Preventing infections in shoulder arthroplasty, particularly P. acnes, remains a challenge. A significant number of revision TSAs are found to have positive cultures for P. acnes creating a significant burden for patients and surgeons

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. Patients and Methods. A quasi-randomised study of 848 patients with an intracapsular fracture of the hip was conducted in one large teaching hospital on two sites. All were treated with a hemiarthroplasty. A total of 448 patients received low dose single-antibiotic impregnated cement (control group) and 400 patients received high dose dual-antibiotic impregnated cement (intervention group). The primary outcome measure was deep SSI at one year after surgery. Results. The rate of deep SSI was 3.5% in the control group and 1.1% in the intervention group (p = 0.041; logistic regression adjusting for age and gender). The overall rate of non-infective surgical complications did not differ between the two groups (unadjusted chi-squared test; p > 0.999). Conclusion. The use of high dose dual-antibiotic impregnated cement in these patients significantly reduces the rate of SSI compared with standard low dose single antibiotic loaded bone cement. Cite this article: Bone Joint J 2016;98-B:1534–1541

Objectives

The objective of this study was to compare the elution characteristics, antimicrobial activity and mechanical properties of antibiotic-loaded bone cement (ALBC) loaded with powdered antibiotic, powdered antibiotic with inert filler (xylitol), or liquid antibiotic, particularly focusing on vancomycin and amphotericin B.

Introduction:. Deep infection after total joint arthroplasty is a devastating complication with reported incidence of 1–3% with projection to increase to 6.8% by 2030. The direct costs of revision surgery due to septic failure are estimated at over $55,000 per case. Antibiotic-Loaded Bone Cement (ALBC) has been proposed as a preventive measure to decrease post-operative infection rates. Its efficacy has been compared with plain bone cement (PBC) in multiple studies. There has been no study to our knowledge examining its efficacy in “high risk” patients. The purpose of this study is to compare infection rates in three cohorts of patients: (1) all patients receiving only PBC, (2) all patients receiving only ALBC, and (3) only “high risk” patients receiving ALBC. Methods:. A standard cement protocol was instituted at our hospital for primary total knee arthroplasties (pTKA). From January 2000 to 2005 all pTKAs were performed with PBC. From February 2005 to May 2010, all pTKAs were performed with ALBC. From June 2010 to March 2012, all patients received regular bone cement unless they had previous diagnoses of rheumatoid arthritis, obesity, and/or diabetes mellitus. Our institutional joint registry was queried and the three cohorts' individual charts were retrospectively reviewed. Infection rates amongst cohorts were compared at 30 days, 6 months, and 1 year from index surgery date utilizing two sided proportion tests. Results:. A total of 3,292 consecutive primary TKAs with full follow up were included. Overall infection rate at one year for the entire study was 0.76%. There were 1,025 patients who received PBC, 1486 ALBC, and 781 in the risk stratified cohort. The 30-day infection rates for cohorts 1, 2, 3 were .0.29%, 0.20%, and 0.13% respectively. The 6-month infection rates for cohorts 1, 2, 3 were 0.39%, 0.54% and 0.38% respectively. The 1-year infection rate for cohorts 1, 2, 3 were 0.78%, 0.61%, and 0.64% respectively. The differences in infection rates between each cohort at all three time intervals were not statistically significant. Conclusions:. Antibiotic loaded bone cement does not significantly decrease infection rates for primary total knee arthroplasty. Even risk stratified usage of ALBC for “high risk” patients may be unnecessary and add undue costs to both the patient and hospital, without any appreciable benefit

INTRODUCTION. Surgical site infections (SSI) in orthopaedics are a major source of postoperative morbidity. Although perioperative antibiotic prophylaxis is a common practice, orthopaedic infections are still high in numbers, due to the increasing use of osteosynthesis material and implants. Implants are avascular and can be easily colonized with biofilm-producing germs. For both, effective prophylaxis and treatment of orthopaedic infections, the right choice of the antibiotics used, the mode of application (only systemic or systemic & local), the timing, dosage and the duration of antibiotics are of extremely high importance. Their inappropriate use does not only lead to failures in prevention or treatment of infections, but may also promote microbial resistance development and may cause serious side effects for the patients. SELECTION & USE OF ANTIBIOTICS. Prophylaxis. Broad-spectrum prophylactic antibiotics should help to eliminate the germs before they start to colonize the implant. For prophylactic purposes the recently published AAOS guidelines [1] recommend the use of cephalosporins, such as cefazolin or cefuroxim, administered within one hour prior to surgery. In cases of suspected beta-lactam allergy, clindamycin or vancomycin can be used. The latter one is also recommended in cases of MRSA colonisation. Due to extended infusion times, vancomycin should be started within two hours prior to incision. In cases of blood loss or long op duration, antibiotic administration must be repeated (e.g. cefazolin, every 2–5 hrs; vancomycin, every 6–12 hrs). There is no evidence of a benefit of continued antibiotic administration past 24 hrs of end of surgery [2]. Treatment. In cases of established infections, use of antibiotics is only considered as an adjuvant to surgical debridement. Typically, the choice of the appropriate antibiotic depends on the bacteria, its antibiotic sensitivity profile and the health state of the patient. A combination of rifampicin & a quinolone (or rifampicin & vancomycin in cases of MRSA) for at least 2 wks up to several months has shown good results [3]. In chronic infections with biofilm involvement, all foreign material must be removed and locally delivered antibiotics via e.g. PMMA as carrier (spacers, PMMA-chains) are of additional clinical benefit. ROLE OF LOCAL ANTIBIOTICS. There is general consensus that PMMA chains or PMMA spacers loaded with specific antibiotics support the eradication of bone and joint infections, because of the high local concentrations achieved. The exact treatment time is, however, variable, ranging from few weeks up to several months. Only small amounts of these local antibiotics are systemically detectable and do not represent a major risk for side effects. Still a matter of debate is the benefit of antibiotic impregnated PMMA for infection prophylaxis. Although common practice in Europe, its routine use in e.g. primary arthroplasty is still discussed in other world regions. Meanwhile, evidence accumulates that joint infection rates are, indeed, lower, if antibiotic loaded bone cement with high initial release rates is routinely used in arthroplasty. 4.

Background. Antibiotic loaded bone cement spacers are used as an adjunct to treatment in 2-stage arthroplasty revisions. If release of the correct choice of antimicrobials is optimised, systemic therapy might be curtailed and emergence of resistance minimised. Aims: To determine the elution period of antimicrobials from bone cement with and without a copolymer, polyvinylpyrrolidone (PVP) and to limit resistance development by the use of two or more antimicrobials. Methods. Triclosan, gentamicin and clindamycin with and without (PVP) in CMW bone cement, was tested against six bacteria using serial plate transfer. Results. While there was little difference between clindamycin and clindamycin with PVP, and between gentamicin and gentamicin with PVP, there was marked enhancement of release of triclosan with PVP. Resistance developed when antimicrobials were used singly but not when used in combination. Conclusion. The addition of water soluble PVP was expected to enhance elution of antimicrobials from bone cement. This occurred with triclosan, a poorly water-soluble agent, but there was no significant difference for gentamicin and clindamycin, which as preferentially water -soluble. Other copolymers are being explored in an attempt to enhance their release. Triclosan used in combination extended the duration of activity against the test bacteria without development of resistance. Combinations of antimicrobials reduce the risk of paradoxical resistance in bone cement

Coloured bone cements have been introduced to make the removal of cement debris easier at the time of primary and revision joint replacement. We evaluated the physical, mechanical and pharmacological effects of adding methylene blue to bone cement with or without antibiotics (gentamicin, vancomycin or both). The addition of methylene blue to plain cement significantly decreased its mean setting time (570 seconds (sd 4) vs 775 seconds (sd 11), p = 0.01), mean compression strength (95.4 MPa (sd 3) vs 100.1 MPa (sd 6), p = 0.03), and mean bending strength (65.2 MPa (sd 5) vs 76.6 MPa (sd 4), p < 0.001) as well as its mean elastic modulus (2744 MPa (sd 97) vs 3281 MPa (sd 110), p < 0.001). The supplementation of the coloured cement with vancomycin and gentamicin decreased its mean bending resistance (55.7 MPa (sd 4) vs 65.2 MPa (sd 5), p < 0.001).The methylene blue significantly decreased the mean release of gentamicin alone (228.2 µg (sd 24) vs 385.5 µg (sd 26), p < 0.001) or in combination with vancomycin (498.5 µg (sd 70) vs 613 µg (sd 25), p = 0.018) from the bone cement. This study demonstrates several theoretical disadvantages of the antibiotic-loaded bone cement coloured with methylene blue.

Infection of a total joint replacement (TJR) is considered a devastating complication, necessitating its complete removal and thorough debridement of the site. Usually at least two surgical interventions and antibiotic treatment within a period of several months are estimated being required for a favourable outcome. It is undoubted that one stage exchange, if successful, would provide the best benefit both for the patient and the society. Still the fear of re-infection dominates the surgeons’ decisions and directs them to multiple stage protocols. However, there is no scientifically based argument for that practice. Successful eradication of infection with two stage procedures is reported to average 80% to 98%, whereas there are no significant differences between revisions with or without antibiotic loaded cement, with short or long term antibiotic therapy, with or without the use of spacers and other differences. On the other hand a literature review of Jackson and Schmalzried (CORR 200) summarizing the results of 1,299 infected hip replacements treated with direct exchange (almost exclusively using antibiotic loaded cement), reports of 1,077 (83%) having been successful. For total knee replacement Jaemson et al. (Acta 2009) could show that the overall success rate in eradication of infection was 73–100% after one-stage revisions. It may be calculated, that adding a second one stage procedure for treating the failed cases the overall result with two operations may improve to > 95%, an outcome which is at least as good as the best results after two stage revisions, while requiring only one surgical intervention for the majority of cases. Spacers have been proven to be useful for improving final functional results compared to temporary resection; however, concerning infection control no benefit could be shown. Dead space management is performed comparably effective by a new prosthesis as with a spacer. In addition a definitive prosthesis is providing increased stability, which a spacer does not. As long as protection against colonization is granted by high local antibiotic concentrations a prostheses is likely to provide better functional results than a spacer. These results suggest, that the major factor for a successful outcome with traditional approaches may be found in the quality of the surgical debridement and dead space management. Failures in all protocols seem to be caused by small fragments of bacterial colonies remaining after debridement, whereas neither systemic antibiotics nor antibiotic loaded bone cement (PMMA) have been able to improve the situation significantly. One stage exchange provides marked reduction of patients discomfort and costs but is performed only rarely due to a multitude of risks and disadvantages, related to the mandatory use of antibiotic loaded cement for fixation. Cemented revisions generally show inferior long term results compared to uncemented techniques; the addition of antibiotics to cement reduces its biomechanical properties. The release of antibiotics from cement is too short-lived and concentrations are too low for reliable eradication of eventually remaining pathogens, especially when they are embedded within biofilms. PMMA has been shown to be the ideal substrate for bacterial attachment and replication of sessile bacterial phenotypes. Aging cement releases antibiotics in subinhibitory amounts, leading to antibiotic resistance of adherent bacteria even years after implantation. Whenever a new prosthesis is implanted into a previously infected site the surgeon must be aware of increased risk of failure, both in single or two stage revisions. Eventual removal therefore should be easy with low risk of additional damage to the bony substance in such a case. On the other hand it should also have potential of a good long term result in case of success. Cemented systems seem to be less likely for that purpose since efficient cementing techniques will result in tight bonding with the underlying bone. Eventual removal such will be time consuming and possibly associated with further damage to the osseous structures. Allograft bone may be impregnated with high loads of antibiotics using special incubation techniques. The storage capacities and pharmacological kinetics of the resulting antibiotic bone compound (ABC) are more advantageous than the ones of antibiotic loaded cement. ABC provides local concentrations exceeding those of cement by more than a 100 fold and efficient release is prolonged for several weeks. The same time they are likely to restore bone stock, which usually is compromised after removal of an infected endoprosthesis. ABC may be combined with uncemented implants which in case of a failure markedly facilitates their removal. There is reduced risk of creating resistances since the stored antibiotics are eluted completely and elution is terminated after several weeks. Based on this technology new protocols for one stage exchange of infected TJR have been established, both for hips and knees. Bone voids surrounding the implants are filled with antibiotic impregnated bone graft; uncemented implants are fixed in original bone. Recent studies indicate an overall success rate of more than 90% without any adverse side effects. Incorporation of allografts appears as after grafting with unimpregnated bone grafts. The favourable results have initiated extension of the technique to simultaneous reconstruction of large septic defects using impregnated bulk allografts. Antibiotic loaded bone graft seems to provide sufficient local antibiosis for protection against colonisation of uncemented implants, the eluted amounts of antibiotics are likely to eliminate biofilm remnants, dead space management is more complete and defects may be reconstructed efficiently. One stage revision such should be at least comparably save as multiple stage procedures, taking advantage of the obvious benefits for patients and economy

Introduction: Infection is a challenging problem in orthopaedic surgery. In oncologic and revision surgery large prosthesis are placed during long procedures, even in patients with immunocompromised status. Infection rates here are reported up to 10%. Infections may necessitate large segmental resections thereby creating large defects. This defect can be filled with antibiotics loaded beads that release the substances locally to sterilise the defect. In recent years solid antibiotic loaded bone cement spacers have been applied. These spacers fill the defect, stabilize the extremity, release antibiotics and keep the soft tissues on their original length. Additionally, the patients will be able to preserve mobile function as well. In small defects prefabricated bone cement spacers temporarily replace the infected hip or knee prosthesis. For larger segmental of terminal defects there are no readily available constructs. Purpose: To report short term outcome of a newly developed customized spacer concept for treatment of large segmental resections after prosthetic infection or osteomyelitis. Material and Methods: We have treated 13 patients with large segmental defects after infection treatment with customized antibiotic bone cement spacers reinforced with strong intra-medullar implants like the Gammanail, the DFN and the UHN. Results: These customized spacers are easy to make, fill the defect, stabilize the extremity, release antibiotics, keep the length of the soft tissues and allow patients to practice and preserve joint function as well. In 11 of 13 patients operated with an interim construct like this, a successful reimplantation of a tumor prosthesis was performed. Conclusion: With customized antibiotic bone cement spacers augmented with a solid implant one can fill the defect, stabilize the extremity, release antibiotics and keep the soft tissues on their original length and keep function as well in infected tumorprosthesis. Successful reimplantation could be performed in 11 of 13 cases

In oncological resections there is a higher risk of infection around the foot and ankle. An infection here can be difficult to treat and easily lead to an amputation due to the limited amount of soft tissue coverage of the region. In three patients an infection developed after resection of a bone tumour in the foot and ankle. In the first case, female 34 years, an epitheloid hemangioepithelioma was excised from the anterior part of the calcaneus, cuboid and lateral os cuneiform. An iliac crest graft was initially used to fill the defect, but got infected. The antibiotic loaded bone cement spacer cured the infection and filled the dead space but was painful. A free vascularised fibula with skin-flap was used successfully to fill the defect and take away the pain. At three-year follow-up there is no pain and full weight bearing, with a nice hypertrophy of the graft. In the second case, a 14-year old girl, there was an Aneu-rismal Bone Cyst (ABC) of the distal tibia with a deep infection after ethibloc injection. The vacuum assisted closure cleaned the wound but a defect resulted. It was successfully filled with an ipsilateral free vascularised fibula with skin-flap. Follow-up shows full function and nice hypertrophy at 24 months. In the third case, male 65 years, a chondrosarcoma grade one (after biopsy) in the cuboid was curetted out. It proved grade two in the definitive histology and furthermore it got infected. The cuboid was excised and a cement spacer was placed. The soft tissues were insufficient to close it properly. A free vascularised fibula with skin-flap was used. The vascularity of the graft was insufficient and the skin-flap did not survive. A vacuum assisted closure was done. He can bear weight and has no pain. The fibula graft is shows some hypertrophy and a fistula persists for 18 months now. We conclude that vascularised free fibula with skinflap can successfully prevent amputation in case of infection in oncological resection of foot and ankle. The fibula reconstructs the bone defect and the skin-flap the soft tissue defect

Copal bone cement loaded with gentamicin and clindamicin was developed recently as a response to the emerging occurrence of gentamicin-resistant strains in periprothetic infections. The objective of this study was to compare the in vitro antibiotic release and antimicrobial efficacy of gentamicin/clindamicin-loaded Copal bone cement and gentamicin-loaded Palacos R-G bone cement, as well as biofilm formation on these cements. In order to determine antibiotic release, cement blocks were placed in phosphate buffer and aliquots were taken at designated times for measurement of antibiotic release. In addition, the bone cement discs were pressed on agar to study the effects of antibiotic release on bacterial growth. Biofilm formation on the different bone cements was also investigated after 1 and 7 days using plate counting and confocal laser scanning microscopy (CLSM). Experiments were done with a gentamicin-sensitive S. aureus and a gentamicin-resistant CNS. Antibiotic release after 672 h from Copal bone cement was more extensive (65% of the clindamycin and 41% of the gentamicin incorporated) than from Palacos R-G (4% of the gentamicin incorporated). The higher antibiotic release from Copal resulted in a stronger and more prolonged inhibition of bacterial growth on agar. Plate counting and CLSM of biofilms grown on the bone cements showed that antibiotic release reduced bacterial viability, most notably close to the cement surface. Moreover, the gentamicin-sensitive S. aureus formed gentamicin-resistant small colony variants on Palacos R-G, and therefore, Copal was much more effective in decreasing biofilm formation than Palacos R-G. Biofilm formation on bone cement could be more effectively reduced by incorporation of a second antibiotic, next to gentamicin. Antibiotic release from the cements had a stronger effect on bacteria close to the cement than on bacteria at the outer surface of the bio-film. Clinically, bone cement with two antibiotics may be more effective than cement loaded with only gentamicin. The clinical efficacy of antibiotic loaded bone cements in combination with systemic antibiotics can be explained because antibiotics released from cements kill predominantly the bacteria in the bottom of the biofilm, whereas systemic antibiotics can only deal with bacteria at the outer surface of the biofilm