Aims. Bacteriophages infect, replicate inside bacteria, and are released from the host through lysis. Here, we evaluate the effects of repetitive doses of the Staphylococcus aureus phage 191219 and gentamicin against haematogenous and early-stage biofilm implant-related infections in Galleria mellonella. Methods. For the haematogenous infection, G. mellonella larvae were implanted with a Kirschner wire (K-wire), infected with S. aureus, and subsequently phages and/or gentamicin were administered. For the early-stage biofilm implant infection, the K-wires were pre-incubated with S. aureus suspension before implantation. After 24 hours, the larvae received phages and/or gentamicin. In both models, the larvae also received daily doses of phages and/or gentamicin for up to five days. The effect was determined by survival analysis for five days and quantitative culture of bacteria after two days of repetitive doses. Results. In the haematogenous infection, a single combined dose of phages and gentamicin, and repetitive injections with gentamicin or in combination with phages, resulted in significantly improved survival rates. In the early-stage biofilm infection, only repetitive combined administration of phages and gentamicin led to a significantly increased survival. Additionally, a significant reduction in number of bacteria was observed in the larvae after receiving repetitive doses of phages and/or gentamicin in both infection models. Conclusion. Based on our results, a single dose of the combination of phages and gentamicin is sufficient to prevent a haematogenous S. aureus implant-related infection, whereas gentamicin needs to be administered daily for the same effect. To treat early-stage S. aureus implant-related infection, repetitive doses of the combination of phages and gentamicin are required. Cite this article: Bone Joint Res 2024;13(8):383–391

Aims. There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). Methods. The CaS/HA composites containing RIF/GEN/VAN, either alone or in combination, were first prepared and their injectability, setting time, and antibiotic elution profiles were assessed. Using a continuous disk diffusion assay, the antibacterial behaviour of the material was tested on both planktonic and biofilm-embedded forms of standard and clinical strains of Staphylococcus aureus for 28 days. Development of bacterial resistance to RIF was determined by exposing the biofilm-embedded bacteria continuously to released fractions of antibiotics from CaS/HA-antibiotic composites. Results. Following the addition of RIF to CaS/HA-VAN/GEN, adequate injectability and setting of the CaS/HA composites were noted. Sustained release of RIF above the minimum inhibitory concentrations of S. aureus was observed until study endpoint (day 35). Only combinations of CaS/HA-VAN/GEN + RIF exhibited antibacterial and antibiofilm effects yielding no viable bacteria at study endpoint. The S. aureus strains developed resistance to RIF when biofilms were subjected to CaS/HA-RIF alone but not with CaS/HA-VAN/GEN + RIF. Conclusion. Our in vitro results indicate that biphasic CaS/HA loaded with VAN or GEN could be used as a carrier for RIF for local delivery in clinically demanding bone infections. Cite this article: Bone Joint Res 2022;11(11):787–802

Aims. Graft infection following anterior cruciate ligament reconstruction (ACLR) may lead to septic arthritis requiring multiple irrigation and debridement procedures, staged revision operations, and prolonged courses of antibiotics. To our knowledge, there are no previous studies reporting on how gentamicin pre-soaking of hamstring grafts influences infection rates following ACLR. We set out to examine this in our study accordingly. Methods. This retrospective study included 2,000 patients (1,156 males and 844 females) who underwent primary ACLR with hamstring autografts between 2007 to 2017. This included 1,063 patients who received pre-soaked saline hamstring grafts for ACLR followed by 937 patients who received pre-soaked gentamicin hamstring grafts for ACLR. All operative procedures were completed by a single surgeon using a standardized surgical technique. Medical notes were reviewed and data relating to the following outcomes recorded: postoperative infection, clinical progress, causative organisms, management received, and outcomes. Results. Superficial wound infection developed in 14 patients (1.31 %) receiving pre-saline soaked hamstring grafts compared to 13 patients (1.38 %) receiving pre-gentamicin soaked hamstring grafts, and this finding was not statistically significant (p = 0.692). All superficial wound infections were treated with oral antibiotics with no further complications. There were no recorded cases of septic arthritis in patients receiving pre-gentamicin soaked grafts compared to nine patients (0.85%) receiving pre-saline soaked grafts, which was statistically significant (p = 0.004). Conclusion. Pre-soaking hamstring autographs in gentamicin does not affect superficial infection rates but does reduce deep intra-articular infection rates compared to pre-soaking hamstring grafts in saline alone. These findings suggest that pre-soaking hamstring autografts in gentamicin provides an effective surgical technique for reducing intra-articular infection rates following ACLR. Cite this article: Bone Jt Open 2021;2(1):66–71

Aims. Continuous local antibiotic perfusion (CLAP) has recently attracted attention as a new drug delivery system for orthopaedic infections. CLAP is a direct continuous infusion of high-concentration gentamicin (1,200 μg/ml) into the bone marrow. As it is a new system, its influence on the bone marrow is unknown. This study aimed to examine the effects of high-concentration antibiotics on human bone tissue-derived cells. Methods. Cells were isolated from the bone tissue grafts collected from six patients using the Reamer-Irrigator-Aspirator system, and exposed to different gentamicin concentrations. Live cells rate, apoptosis rate, alkaline phosphatase (ALP) activity, expression of osteoblast-related genes, mineralization potential, and restoration of cell viability and ALP activity were examined by in vitro studies. Results. The live cells rate (the ratio of total number of cells in the well plate to the absorbance-measured number of live cells) was significantly decreased at ≥ 500 μg/ml of gentamicin on day 14; apoptosis rate was significantly increased at ≥ 750 μg/ml, and ALP activity was significantly decreased at ≥ 750 μg/ml. Real-time reverse transcription-polymerase chain reaction results showed no significant decrease in the ALP and activating transcription factor 4 transcript levels at ≥ 1,000 μg/ml on day 7. Mineralization potential was significantly decreased at all concentrations. Restoration of cell viability was significantly decreased at 750 and 1,000 μg/ml on day 21 and at 500 μg/ml on day 28, and ALP activity was significantly decreased at 500 μg/ml on day 28. Conclusion. Our findings suggest that the exposure concentration and duration of antibiotic administration during CLAP could affect cell functions. However, further in vivo studies are needed to determine the optimal dose in a clinical setting. Cite this article: Bone Joint Res 2024;13(3):91–100

Aims. To investigate the bone penetration of intravenous antibiotic prophylaxis with flucloxacillin and gentamicin during hip and knee arthroplasty, and their efficacy against Staphylococcus (S.) aureus and S. epidermidis. Patients and Methods. Bone samples from the femoral head, neck and acetabulum were collected from 18 patients undergoing total hip arthroplasty (THA) and from the femur and tibia in 21 patients during total knee arthroplasty (TKA). The concentration of both antibiotics in the samples 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 against both the minimum inhibitory concentration 50, and the more stringent epidemiological cutoff value for resistance (ECOFF). Results. The bone penetration of gentamicin was higher than flucloxacillin. Relative to ECOFF, flucloxacillin concentrations were effective against S. aureus and S. epidermidis in all THAs and 20 (95%) TKAs. Gentamicin concentrations were effective against S. epidermidis in all bone samples. Gentamicin was effective against S. aureus in 11 (61.1%) femoral neck samples in THA. Effective concentrations of gentamicin against S. aureus were only achieved in four (19%) femoral and six (29%) tibial samples in TKA. Conclusion. Flucloxacillin and gentamicin were found to penetrate bone during THA and TKA. Gentamicin was effective against S. epidermidis in both THA and TKA, while levels were subtherapeutic against S. aureus in most TKAs. Bone penetration of both antibiotics was less in TKA than THA, and may relate to the use of a tourniquet. Using this antibiotic combination, effective cover against the two common infective organisms was achieved in all THAs and all but one TKA. Cite this article: Bone Joint J 2017;99-B:358–64

Objectives . The objective of this study is to determine an optimal antibiotic-loaded bone cement (ALBC) for infection prophylaxis in total joint arthroplasty (TJA). Methods. We evaluated the antibacterial effects of polymethylmethacrylate (PMMA) bone cements loaded with vancomycin, teicoplanin, ceftazidime, imipenem, piperacillin, gentamicin, and tobramycin against methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staph. aureus (MRSA), coagulase-negative staphylococci (CoNS), Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Standardised cement specimens made from 40 g PMMA loaded with 1 g antibiotics were tested for elution characteristics, antibacterial activities, and compressive strength in vitro. . Results. The ALBC containing gentamicin provided a much longer duration of antibiotic release than those containing other antibiotic. Imipenem-loading on the cement had a significant adverse effect on the compressive strength of the ALBC, which made it insufficient for use in prosthesis fixation. All of the tested antibiotics maintained their antibacterial properties after being mixed with PMMA. The gentamicin-loaded ALBC provided a broad antibacterial spectrum against all the test organisms and had the greatest duration of antibacterial activity against MSSA, CoNS, P. aeruginosa and E. coli. . Conclusion. When considering the use of ALBC as infection prophylaxis in TJA, gentamicin-loaded ALBC may be a very effective choice. Cite this article: Bone Joint Res 2013;2:220–6

Aims. Excision of chronic osteomyelitic bone creates a dead space which must be managed to avoid early recurrence of infection. Systemic antibiotics cannot penetrate this space in high concentrations, so local treatment has become an attractive adjunct to surgery. The aim of this study was to present the mid- to long-term results of local treatment with gentamicin in a bioabsorbable ceramic carrier. Methods. A prospective series of 100 patients with Cierny-Mader Types III and IV chronic ostemyelitis, affecting 105 bones, were treated with a single-stage procedure including debridement, deep tissue sampling, local and systemic antibiotics, stabilization, and immediate skin closure. Chronic osteomyelitis was confirmed using strict diagnostic criteria. The mean follow-up was 6.05 years (4.2 to 8.4). Results. At final follow-up, six patients (six bones) had recurrent infection; thus 94% were infection-free. Three infections recurred in the first year, two in the second year, and one 4.5 years postoperatively. Recurrence was not significantly related to the physiological class of the patient (1/20 Class A (5%) vs 5/80 Class B (6.25%); p = 0.833), nor was it significantly related to the aetiology of the infection, the organisms which were cultured or the presence of nonunion before surgery (1/10 with nonunion (10%) vs 5/90 without nonunion (5.6%); p = 0.570). Organisms with intermediate or high-grade resistance to gentamicin were significantly more likely in polymicrobial infections (9/21; 42.8%) compared with monobacterial osteomyelitis (7/79 (8.9%); p < 0.001). However, recurrence was not significantly more frequent when a resistant organism was present (1/16 for resistant cases (6.25%) vs 5/84 in those with a microbiologically sensitive infection (5.95%); p = 0.958). Conclusion. We found that a single-stage protocol, including the use of a high-delivery local antibiotic ceramic carrier, was effective over a period of several years. The method can be used in a wide range of patients, including those with significant comorbidities and an infected nonunion. Cite this article: Bone Joint J 2022;104-B(9):1095–1100

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

Aims. Prophylactic antibiotic regimens for elective primary total hip and knee arthroplasty vary widely across hospitals and trusts in the UK. This study aimed to identify antibiotic prophylaxis regimens currently in use for elective primary arthroplasty across the UK, establish variations in antibiotic prophylaxis regimens and their impact on the risk of periprosthetic joint infection (PJI) in the first-year post-index procedure, and evaluate adherence to current international consensus guidance. Methods. The guidelines for the primary and alternative recommended prophylactic antibiotic regimens in clean orthopaedic surgery (primary arthroplasty) for 109 hospitals and trusts across the UK were sought by searching each trust and hospital’s website (intranet webpages), and by using the MicroGuide app. The mean cost of each antibiotic regimen was calculated using price data from the British National Formulary (BNF). Regimens were then compared to the 2018 Philadelphia Consensus Guidance, to evaluate adherence to international guidance. Results. The primary choice and dosing of the prophylactic antimicrobial regimens varied widely. The two most used regimens were combined teicoplanin and gentamicin, and cefuroxime followed by two or three doses of cefuroxime eight-hourly, recommended by 24 centres (22.02%) each. The alternative choice and dosing of the prophylactic antimicrobial regimen also varied widely across the 83 centres with data available. Prophylaxis regimens across some centres fail to cover the likeliest causes of surgical site infection (SSI). Five centres (4.59%) recommend co-amoxiclav, which confers no Staphylococcus coverage, while 33 centres (30.28%) recommend cefuroxime, which confers no Enterococcus coverage. Limited adherence to 2018 Philadelphia Consensus Guidance was observed, with 67 centres (61.50%) not including a cephalosporin in their guidance. Conclusion. This analysis of guidance on antimicrobial prophylaxis in primary arthroplasty across 109 hospitals and trusts in the UK has identified widespread variation in primary and alternative antimicrobial regimens currently recommended. Cite this article: Bone Jt Open 2023;4(10):742–749

Bone cement containing gentamicin may release antibiotic when fractured during revision operations. Tissue samples taken during surgery may be contaminated by gentamicin and give inaccurate microbiological assessment. We studied five patients in whom cement containing gentamicin had been used in the primary procedure. During revision hip replacement, samples of joint fluid, tissues and cement were taken both before and after disruption of the cement. With the exception of one sample of joint fluid, low concentrations of gentamicin were recorded in the samples taken before the cement was disrupted, but after disruption the specimens contained gentamicin at concentrations high enough to inhibit or prevent growth of sensitive organisms. The cement contained very high levels up to ten years after insertion. Our findings suggest that no reliance can be placed on the microbiological assessment of specimens taken once cement splitting has started and that specimens should therefore be taken as early as possible

We performed a randomised, radiostereometric study comparing two different bone cements, one of which has been sparsely clinically documented. Randomisation of 60 total hip replacements (57 patients) into two groups of 30 was undertaken. All the patients were operated on using a cemented Charnley total hip replacement, the only difference between groups being the bone cement used to secure the femoral component. The two cements used were Palamed G and Palacos R with gentamicin. The patients were followed up with repeated clinical and radiostereometric examinations for two years to assess the micromovement of the femoral component and the clinical outcome. The mean subsidence was 0.18 mm and 0.21 mm, and the mean internal rotation was 1.7° and 2.0° at two years for the Palamed G and Palacos R with gentamicin bone cements, respectively. We found no statistically significant differences between the groups. Micromovement occurred between the femoral component and the cement, while the cement mantle was stable inside the bone. The Harris hip score improved from a mean of 38 points (14 to 54) and 36 (10 to 57) pre-operatively to a mean of 92 (77 to 100) and 91 (63 to 100) at two years in the Palamed G and Palacos R groups, respectively. No differences were found between the groups. Both bone cements provided good initial fixation of the femoral component and good clinical results at two years

Despite widespread use of gentamicin beads in the treatment of chronic infections of bone and soft tissue, no serious complications have been reported. This report describes a rupture of the femoral vein which occurred during the attempted removal of a chain of beads after radical excision of a chronically discharging Girdlestone arthroplasty. The patient later had a disarticulation at the hip. In the light of our experience with this and other cases we offer some suggestions as to the positioning of gentamicin beads, as well as the timing and method of their extraction

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

Gentamicin incorporated in beads of polymethylmethacrylate has been shown capable of being released over a period of several months in concentrations sufficiently high to control most pathogens. The therapeutic efficacy of such beads has been demonstrated in a model of osteomyelitis of the femur in the dog. Good tolerance has been shown, both in the animal model and in tissue cultures. In forty-one patients with infection of either bone or soft tissue, mainly of the lower limb, the findings were similar. The concentrations in serum and urine were low, which excludes side-effects. The insertion of gentamicin-PMMA beads may prove to be a valuable new form of local antibiotic therapy

Aims

Vancomycin is commonly added to acrylic bone cement during revision arthroplasty surgery. Proprietary cement preparations containing vancomycin are available, but are significantly more expensive. We investigated whether the elution of antibiotic from ‘home-made’ cement containing vancomycin was comparable with more expensive commercially available vancomycin impregnated cement.

Aims. Periprosthetic joint infection (PJI) is a debilitating condition with a substantial socioeconomic burden. A novel autologous blood glue (ABG) has been developed, which can be prepared during surgery and sprayed onto prostheses at the time of implantation. The ABG can potentially provide an antimicrobial coating which will be effective in preventing PJI, not only by providing a physical barrier but also by eluting a well-known antibiotic. Hence, this study aimed to assess the antimicrobial effectiveness of ABG when impregnated with gentamicin and stem cells. Methods. Gentamicin elution from the ABG matrix was analyzed and quantified in a time-dependent manner. The combined efficiency of gentamicin and ABG as an anti-biofilm coating was investigated on titanium disks. Results. ABG-gentamicin was bactericidal from 10 μg/ml and could release bactericidal concentrations over seven days, preventing biofilm formation. A concentration of 75 μg/ml of gentamicin in ABG showed the highest bactericidal effect up to day 7. On titanium disks, a significant bacterial reduction on ABG-gentamicin coated disks was observed when compared to both uncoated (mean 2-log reduction) and ABG-coated (mean 3-log reduction) disks, at days 3 and 7. ABG alone exhibited no antimicrobial or anti-biofilm properties. However, a concentration of 75 μg/ml gentamicin in ABG sustains release over seven days and significantly reduced biofilm formation. Its use as an implant coating in patients with a high risk of infection may prevent bacterial adhesion perioperatively and in the early postoperative period. Conclusion. ABG’s use as a carrier for stem cells was effective, as it supported cell growth. It has the potential to co-deliver compatible cells, drugs, and growth factors. However, ABG-gentamicin’s potential needs to be further justified using in vivo studies. Cite this article: Bone Joint Res 2020;9(12):848–856

Aims. The aim of this study was to develop a single-layer hybrid organic-inorganic sol-gel coating that is capable of a controlled antibiotic release for cementless hydroxyapatite (HA)-coated titanium orthopaedic prostheses. Methods. Coatings containing gentamicin at a concentration of 1.25% weight/volume (wt/vol), similar to that found in commercially available antibiotic-loaded bone cement, were prepared and tested in the laboratory for: kinetics of antibiotic release; activity against planktonic and biofilm bacterial cultures; biocompatibility with cultured mammalian cells; and physical bonding to the material (n = 3 in all tests). The sol-gel coatings and controls were then tested in vivo in a small animal healing model (four materials tested; n = 6 per material), and applied to the surface of commercially pure HA-coated titanium rods. Results. The coating released gentamicin at > 10 × minimum inhibitory concentration (MIC) for sensitive staphylococcal strains within one hour thereby potentially giving effective prophylaxis for arthroplasty surgery, and showed > 99% elution of the antibiotic within the coating after 48 hours. There was total eradication of both planktonic bacteria and established bacterial biofilms of a panel of clinically relevant staphylococci. Mesenchymal stem cells adhered to the coated surfaces and differentiated towards osteoblasts, depositing calcium and expressing the bone marker protein, osteopontin. In the in vivo small animal bone healing model, the antibiotic sol-gel coated titanium (Ti)/HA rod led to osseointegration equivalent to that of the conventional HA-coated surface. Conclusion. In this study we report a new sol-gel technology that can release gentamicin from a bioceramic-coated cementless arthroplasty material. In vitro, local gentamicin levels are in excess of what can be achieved by antibiotic-loaded bone cement. In vivo, bone healing in an animal model is not impaired. This, thus, represents a biomaterial modification that may have the potential to protect at-risk patients from implant-related deep infection. Cite this article: Bone Joint J 2021;103-B(3):522–529

Aims. The aim of this study was to determine if the local delivery of vancomycin and tobramycin in primary total knee arthroplasty (TKA) can achieve intra-articular concentrations exceeding the minimum inhibitory concentration thresholds for bacteria causing acute prosthetic joint infection (PJI). Methods. Using a retrospective single-institution database of all primary TKAs performed between January 1 2014 and May 7 2019, we identified patients with acute PJI that were managed surgically within 90 days of the initial procedure. The organisms from positive cultures obtained at the time of revision were tested for susceptibility to gentamicin, tobramycin, and vancomycin. A prospective study was then performed to determine the intra-articular antibiotic concentration on postoperative day one after primary TKA using one of five local antibiotic delivery strategies with tobramycin and/or vancomycin mixed into the polymethylmethacrylate (PMMA) or vancomycin powder. Results. A total of 19 patients with acute PJI after TKA were identified and 29 unique bacterial isolates were recovered. The mean time to revision was 37 days (6 to 84). Nine isolates (31%) were resistant to gentamicin, ten (34%) were resistant to tobramycin, and seven (24%) were resistant to vancomycin. Excluding one Fusobacterium nucleatum, which was resistant to all three antibiotics, all isolates resistant to tobramycin or gentamicin were susceptible to vancomycin and vice versa. Overall, 2.4 g of tobramycin hand-mixed into 80 g of PMMA and 1 g of intra-articular vancomycin powder consistently achieved concentrations above the minimum inhibitory concentrations of susceptible organisms. Conclusion. One-third of bacteria causing acute PJI after primary TKA were resistant to the aminoglycosides commonly mixed into PMMA, and one-quarter were resistant to vancomycin. With one exception, all bacteria resistant to tobramycin were susceptible to vancomycin and vice versa. Based on these results, the optimal cover for organisms causing most cases of acute PJI after TKA can be achieved with a combination of tobramycin mixed in antibiotic cement, and vancomycin powder. Cite this article: Bone Joint J 2020;102-B(6 Supple A):163–169

Aims. Dead-space management, following dead bone resection, is an important element of successful chronic osteomyelitis treatment. This study compared two different biodegradable antibiotic carriers used for dead-space management, and reviewed clinical and radiological outcomes. All cases underwent single-stage surgery and had a minimum one-year follow-up. Methods. A total of 179 patients received preformed calcium sulphate pellets containing 4% tobramycin (Group OT), and 180 patients had an injectable calcium sulphate/nanocrystalline hydroxyapatite ceramic containing gentamicin (Group CG). Outcome measures were infection recurrence, wound leakage, and subsequent fracture involving the treated segment. Bone-void filling was assessed radiologically at a minimum of six months post-surgery. Results. The median follow-up was 4.6 years (interquartile range (IQR) 3.2 to 5.4; range 1.3 to 10.5) in Group OT compared to 4.9 years (IQR 2.1 to 6.0; range 1.0 to 8.3) in Group CG. The groups had similar defect sizes following excision (both mean 10.9 cm. 3. (1 to 30)). Infection recurrence was higher in Group OT (20/179 (11.2%) vs 8/180 (4.4%), p = 0.019) than Group CG, as was early wound leakage (33/179 (18.4%) vs 18/180 (10.0%), p = 0.024) and subsequent fracture (11/179 (6.1%) vs 1.7% (3/180), p = 0.032). Group OT cases had an odds ratio 2.9-times higher of developing any one of these complications, compared to Group CG (95% confidence interval 1.74 to 4.81, p < 0.001). The mean bone-void healing in Group CG was better than in Group OT, in those with ≥ six-month radiological follow-up (73.9% vs 40.0%, p < 0.001). Conclusion. Local antibiotic carrier choice affects outcome in chronic osteomyelitis surgery. A biphasic injectable carrier with a slower dissolution time was associated with better radiological and clinical outcomes compared to a preformed calcium sulphate pellet carrier. Cite this article: Bone Joint Res 2023;12(7):412–422

Objectives. The optimal protocol for antibiotic loading in the articulating cement spacers for the treatment of prosthetic joint infection (PJI) remains controversial. The objective of the present study was to investigate the effectiveness of articulating cement spacers loaded with a new combination of antibiotics. Methods. A retrospective cohort study involving 114 PJI cases treated with implantation of an articulating cement spacer between 2005 and 2016 was performed. The treatment outcomes of the conventional protocol (i.e. gentamicin and vancomycin (GV protocol)) were compared with those reported using the sophisticated antibiotic-loading protocol (i.e. vancomycin, meropenem, and amphotericin (VMA protocol)). Results. There were 62 and 52 PJI cases treated with the GV and VMA protocols, respectively. Antimicrobial susceptibility testing revealed that 22/78 of all isolates (28.2%) in this series were resistant to gentamicin, whereas there were no vancomycin-, meropenem-, or amphotericin-resistant strains. The overall infection recurrence rates were 17.7% (11/62) and 1.9% (1/52), respectively (p = 0.006). In patients with a negative preoperative culture, there was no infection recurrence reported in the VMA cohort (0/45 (0%) vs 10/54 (18.5%) in the GV cohort; p = 0.002). Multivariate analysis indicated that the VMA protocol correlated with a decreased risk of infection recurrence compared with the GV protocol (p = 0.025). Conclusion. The sophisticated VMA protocol for the loading of antibiotics in articulating cement spacers, as part of a two-stage exchange, was associated with a reduced rate of infection recurrence. This proposed protocol appears to be safe and effective, especially in patients with negative culture results prior to the first-stage operation. Cite this article: Bone Joint Res 2019;8:526–534

Objectives. The optimal protocol for antibiotic loading in the articulating cement spacers for the treatment of prosthetic joint infection (PJI) remains controversial. The objective of the present study was to investigate the effectiveness of articulating cement spacers loaded with a new combination of antibiotics. Methods. A retrospective cohort study involving 114 PJI cases treated with implantation of an articulating cement spacer between 2005 and 2016 was performed. The treatment outcomes of the conventional protocol (i.e. gentamicin and vancomycin (GV protocol)) were compared with those reported using the sophisticated antibiotic-loading protocol (i.e. vancomycin, meropenem, and amphotericin (VMA protocol)). Results. There were 62 and 52 PJI cases treated with the GV and VMA protocols, respectively. Antimicrobial susceptibility testing revealed that 22/78 of all isolates (28.2%) in this series were resistant to gentamicin, whereas there were no vancomycin-, meropenem-, or amphotericin-resistant strains. The overall infection recurrence rates were 17.7% (11/62) and 1.9% (1/52), respectively (p = 0.006). In patients with a negative preoperative culture, there was no infection recurrence reported in the VMA cohort (0/45 (0%) vs 10/54 (18.5%) in the GV cohort; p = 0.002). Multivariate analysis indicated that the VMA protocol correlated with a decreased risk of infection recurrence compared with the GV protocol (p = 0.025). Conclusion. The sophisticated VMA protocol for the loading of antibiotics in articulating cement spacers, as part of a two-stage exchange, was associated with a reduced rate of infection recurrence. This proposed protocol appears to be safe and effective, especially in patients with negative culture results prior to the first-stage operation. Cite this article: Bone Joint Res 2019;8:526–534

We investigated whether the indentation of bone cement spacers used in revision of infected joint arthroplasty with a MacDonald dissector increased the elution of antibiotic in vitro. A total of 24 cement discs containing either 0.17 g (0.88% w/w), 0.25 g (1.41% w/w), or 0.33 g (1.75% w/w) gentamicin of constant size were made. Of these, 12 were indented with the dissector. Each disc was immersed in ammonium acetate buffer in a sealed container, and fluid from each container was sampled at zero, one, three, six, 24, 48 and 72 hours and at one, and two weeks. The concentration of gentamicin in the fluid was analysed using high performance liquid chromatography mass spectrometry. . The fluid sampled at 72 hours from the indented discs containing 0.17 g gentamicin (0.88% w/w) contained a mean of 113 mcg/ml (90.12 to 143.5) compared with 44.5 mcg/ml (44.02 to 44.90) in the fluid sampled from the plain discs (p = 0.012). In discs containing 0.33 g gentamicin (1.75% w/w), the concentration eluted from the indented discs at 72 hours was a mean of 316 mcg/ml (223 to 421) compared with a mean of 118 mcg/ml (100 to 140) from the plain discs (p < 0.001). . At two weeks, these significant differences persisted. At nine weeks the indented discs eluted a greater concentration for all gentamicin doses, but the difference was only significant for the discs containing 0.17 g (0.88% w/w, p = 0.006). However if the area under the curve is taken as a measure of the total antibiotic eluted, the indented discs eluted more gentamicin than the plain discs for the 0.17 g (0.88% w/w, p = 0.031), the 0.25 g (1.41% w/w, p < 0.001) and the 0.33 g (1.75% w/w, p < 0.001) discs. . When preparing antibiotic spacers for use in staged revision arthroplasty surgery we recommend indenting the spacer with a MacDonald dissector to increase the elution of antibiotic. Cite this article: Bone Joint J 2015;97-B:1519–24

Objective . A clinical investigation into a new bone void filler is giving first data on systemic and local exposure to the anti-infective substance after implantation. Method . A total of 20 patients with post-traumatic/post-operative bone infections were enrolled in this open-label, prospective study. After radical surgical debridement, the bone cavity was filled with this material. The 21-day hospitalisation phase included determination of gentamicin concentrations in plasma, urine and wound exudate, assessment of wound healing, infection parameters, implant resorption, laboratory parameters, and adverse event monitoring. The follow-up period was six months. . Results . Systemic exposure to gentamicin after implantation was very low as local gentamicin concentrations were measured in wound exudate after six to ten hours. There were no signs of infectious complication throughout the clinical phase. Four patients had recurrent infections several weeks to months after implantation. The outcome was deemed successful by remission of infection in 16 (80%) of these problematic long-term treated patients. Safety laboratory measurements did not indicate nephrotoxic or hepatotoxic effects. . Conclusions . Local application of calcium sulphate/carbonate bone void filler comprising gentamicin revealed sufficient active local levels of the antibiotic by simultaneous significant low systemic exposure in patients with mostly chronic osteomyelitis/osteitis. The material was safe and well tolerated. Cite this article: Bone Joint Res 2014;3:223–9

Aims. We propose a state-of-the-art temporary spacer, consisting of a cobalt-chrome (CoCr) femoral component and a gentamicin-eluting ultra-high molecular weight polyethylene (UHMWPE) tibial insert, which can provide therapeutic delivery of gentamicin, while retaining excellent mechanical properties. The proposed implant is designed to replace conventional spacers made from bone cement. Methods. Gentamicin-loaded UHMWPE was prepared using phase-separated compression moulding, and its drug elution kinetics, antibacterial, mechanical, and wear properties were compared with those of conventional gentamicin-loaded bone cement. Results. Gentamicin-loaded UHMWPE tibial components not only eradicated planktonic Staphylococcus aureus, but also prevented colonization of both femoral and tibial components. The proposed spacer possesses far superior mechanical and wear properties when compared with conventional bone cement spacers. Conclusion. The proposed gentamicin-eluting UHMWPE spacer can provide antibacterial efficacy comparable with currently used bone cement spacers, while overcoming their drawbacks. The novel spacer proposed here has the potential to drastically reduce complications associated with currently used bone cement spacers and substantially improve patients’ quality of life during the treatment. Cite this article: Bone Joint J 2020;102-B(6 Supple A):151–157

Aims. CERAMENT|G is an absorbable gentamicin-loaded biocomposite used as an on-site vehicle of antimicrobials for the treatment of chronic osteomyelitis. The purpose of the present study was to investigate the sole effect of CERAMENT|G, i.e. without additional systemic antimicrobial therapy, in relation to a limited or extensive debridement of osteomyelitis lesions in a porcine model. Methods. Osteomyelitis was induced in nine pigs by inoculation of 10. 4. colony-forming units (CFUs) of Staphylococcus aureus into a drill hole in the right tibia. After one week, the pigs were allocated into three groups. Group A (n = 3) received no treatment during the study period (19 days). Groups B (n = 3) and C (n = 3) received limited or extensive debridement seven days postinoculation, respectively, followed by injection of CERAMENT|G into the bone voids. The pigs were euthanized ten (Group C) and 12 (Group B) days after the intervention. Results. All animals presented confirmatory signs of bone infection post-mortem. The estimated amount of inflammation was substantially greater in Groups A and B compared to Group C. In both Groups B and C, peptide nucleic acid fluorescence in situ hybridization (PNA FISH) of CERAMENT|G and surrounding bone tissue revealed bacteria embedded in an opaque matrix, i.e. within biofilm. In addition, in Group C, the maximal measured post-mortem gentamicin concentrations in CERAMENT|G and surrounding bone tissue samples were 16.6 μg/ml and 6.2 μg/ml, respectively. Conclusion. The present study demonstrates that CERAMENT|G cannot be used as a standalone alternative to extensive debridement or be used without the addition of systemic antimicrobials. Cite this article: Bone Joint Res 2020;9(7):394–401

Aims. To characterize the intracellular penetration of osteoblasts and osteoclasts by methicillin-resistant Staphylococcus aureus (MRSA) and the antibiotic and detergent susceptibility of MRSA in bone. Methods. Time-lapse confocal microscopy was used to analyze the interaction of MRSA strain USA300 with primary murine osteoblasts and osteoclasts. The effects of early and delayed antibiotic treatments on intracellular and extracellular bacterial colony formation and cell death were quantified. We tested the effects of cefazolin, gentamicin, vancomycin, tetracycline, rifampicin, and ampicillin, as well as agents used in surgical preparation and irrigation. Results. MRSA infiltrated bone-resident cells within 15 to 30 minutes. Penetration was most effectively prevented with early (i.e. 30 minutes) antibiotic administration. The combined administration of rifampicin with other antibiotics potentiated their protective effects against MRSA-induced cytotoxicity and most significantly reduced extracellular bacterial bioburden. Gentamicin-containing compounds were most effective in reducing intracellular MRSA bioburden. Of the surgical preparation agents evaluated, betadine reduced in vitro MRSA growth to the greatest extent. Conclusion. The standard of care for open fractures involves debridement and antibiotics within the first six hours of injury but does not account for the window in which bacteria penetrate cells. Antibiotics must be administered as early as possible after injury or prior to incision to prevent intracellular infestation. Rifampicin can potentiate the capacity of antibiotic regimens to reduce MRSA-induced cytotoxicity. Cite this article:Bone Joint Res. 2020;9(2):49–59

Clinical experience indicates the beneficial effects of antibiotic-loaded bone cement. Although in vitro studies have shown the formation of a biofilm on its surface they have not considered the gap between the cement and the bone. We have investigated bacterial survival in that gap. Samples with gaps 200 μm wide were made of different bone cements. These were stored dry (‘pre-elution’) or submersed in phosphate-buffered saline to simulate the initial release of gentamicin (‘post-elution’). The gaps were subsequently inoculated with bacteria, which had been isolated from infected orthopaedic prostheses and assessed for their sensitivity to gentamicin. Bacterial survival was measured 24 hours after inoculation. All the strains survived in plain cements. In the pre-elution gentamicin-loaded cements only the most gentamicin-resistant strain, CN5115, survived, but in post-elution samples more strains did so, depending on the cement tested. Although high concentrations of gentamicin were demonstrated in the gaps only the gentamicin-sensitive strains were killed. This could explain the increased prevalence of gentamicin-resistant infections which are seen clinically

Aims. Methicillin-resistant Staphylococcus aureus (MRSA) can cause wound infections via a ‘Trojan Horse’ mechanism, in which neutrophils engulf intestinal MRSA and travel to the wound, releasing MRSA after apoptosis. The possible role of intestinal MRSA in prosthetic joint infection (PJI) is unknown. Methods. Rats underwent intestinal colonization with green fluorescent protein (GFP)-tagged MRSA by gavage and an intra-articular wire was then surgically implanted. After ten days, the presence of PJI was determined by bacterial cultures of the distal femur, joint capsule, and implant. We excluded several other possibilities for PJI development. Intraoperative contamination was excluded by culturing the specimen obtained from surgical site. Extracellular bacteraemia-associated PJI was excluded by comparing with the infection rate after intravenous injection of MRSA or MRSA-carrying neutrophils. To further support this theory, we tested the efficacy of prophylactic membrane-permeable and non-membrane-permeable antibiotics in this model. Results. After undergoing knee surgery eight or 72 hours after colonization, five out of 20 rats (25.0%) and two out of 20 rats (10.0%) developed PJI, respectively. Strikingly, 11 out of 20 rats (55.0%) developed PJI after intravenous injection of MRSA-carrying neutrophils that were isolated from rats with intestinal MRSA colonization. None of the rats receiving intravenous injections of MRSA developed PJI. These results suggest that intestinal MRSA carried by neutrophils could cause PJI in our rat model. Ten out of 20 (50.0%) rats treated with non-membrane-permeable gentamicin developed PJI, whereas only one out of 20 (5.0%) rats treated with membrane-permeable linezolid developed PJI. Conclusion. Neutrophils as carriers of intestinal MRSA may play an important role in PJI development. Cite this article:Bone Joint Res. 2020;9(4):152–161

Bone cements produced by different manufacturers vary in their mechanical properties and antibiotic elution characteristics. Small changes in the formulation of a bone cement, which may not be apparent to surgeons, can also affect these properties. The supplier of Palacos bone cement with added gentamicin changed in 2005. We carried out a study to examine the mechanical characteristics and antibiotic elution of Schering-Plough Palacos, Heraeus Palacos and Depuy CMW Smartset bone cements. Both Heraeus Palacos and Smartset bone cements performed significantly better than Schering-Plough Palacos in terms of mechanical characteristics, with and without additional vancomycin (p < 0.001). All cements show a deterioration in flexural strength with increasing addition of vancomycin, albeit staying above ISO minimum levels. Both Heraeus Palacos and Smartset elute significantly more gentamicin cumulatively than Schering-Plough Palacos. Smartset elutes significantly more vancomycin cumulatively than Heraeus Palacos. The improved antibiotic elution characteristics of Smartset and Heraeus Palacos are not associated with a deterioration in mechanical properties. Although marketed as the ‘original’ Palacos, Heraeus Palacos has significantly altered mechanical and antibiotic elution characteristics compared with the most commonly-used previous version

Antibiotics are often administrated prophylactically in spinal procedures to reduce the risk of infection of the disc space. It is still not known which antibiotics are able to penetrate the intervertebral disc effectively. In a prospective, randomised, double-blind clinical study, we examined the penetration of the intervertebral discs of two commonly used antibiotics, cefuroxime and gentamicin. The patients, randomised into two groups, received either 1.5 g of cefuroxime or 5 mg/kg of gentamicin prophylactically two hours before their intervertebral discs were removed. A specimen of blood, from which serum antibiotic levels were determined, was obtained at the time of discectomy. Therapeutic levels of antibiotic were detectable in the intervertebral discs of the ten patients who received gentamicin. Only two of the ten patients (20%) who received cefuroxime had a quantifiable level of antibiotic in their discs although therapeutic serum levels of cefuroxime were found in all ten patients. Our results show that cefuroxime does not diffuse into human intervertebral discs as readily as gentamicin. It is possible that the charge due to ionisable groups on the antibiotics can influence the penetration of the antibiotics. We therefore recommend the use of gentamicin in a single prophylactic dose for all spinal procedures in order to reduce the risk of discitis

A randomised, double-blind study was performed in two groups of 15 patients undergoing total hip replacements, using antibiotic-loaded acrylic cement containing 0.5 g and 1.0 g gentamicin base respectively per 40 g pack of powdered polymer. Postoperatively, the gentamicin levels in the blood, in the urine and in the wound drainage fluid were measured. In both groups of patients, the serum gentamicin concentrations were low whereas the wound drainage fluid contained highly effective antibacterial concentrations. Serum, urine and wound secretion levels showed approximately two-fold higher concentrations in the group of patients receiving the higher gentamicin load

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. Methods. In this study, a total of 38 frequently used antibiotic agents were maintained at 37°C in saline solution, and degradation and antibacterial activity assessed over six weeks. The impact of an initial supplementary heat exposure mimicking exothermically curing bone cement was also tested as this material is commonly used as a local delivery vehicle. Antibiotic degradation was assessed by liquid chromatography coupled to mass spectrometry, or by immunoassays, as appropriate. Antibacterial activity over time was determined by the Kirby-Bauer disk diffusion assay. Results. The heat exposure mimicking curing bone cement had minimal effect on stability for most antibiotics, except for gentamicin which experienced approximately 25% degradation as measured by immunoassay. Beta-lactam antibiotics were found to degrade quite rapidly at 37°C regardless of whether there was an initial heat exposure. Excellent long-term stability was observed for aminoglycosides, glycopeptides, tetracyclines and quinolones under both conditions. Conclusions. This study provides a valuable dataset for orthopaedic surgeons considering local application of antibiotics, and for material scientists looking to develop next-generation controlled or extended-release antibiotic carriers. Cite this article: E. Samara, T. F. Moriarty, L. A. Decosterd, R. G. Richards, E. Gautier, P. Wahl. Antibiotic stability over six weeks in aqueous solution at body temperature with and without heat treatment that mimics the curing of bone cement. Bone Joint J 2017;6:296–306. DOI: 10.1302/2046-3758.65.BJR-2017-0276.R1

Infection of orthopaedic implants is a significant problem, with increased antibiotic resistance of adherent ‘biofilm’ bacteria causing difficulties in treatment. We have investigated the in vitro effect of a pulsed electromagnetic field (PEMF) on the efficacy of antibiotics in the treatment of infection of implants. Five-day biofilms of Staphylococcus epidermidis were grown on the tips of stainless-steel pegs. They were exposed for 12 hours to varying concentrations of gentamicin or vancomycin in microtitre trays at 37°C and 5% CO. 2. The test group were exposed to a PEMF. The control tray was not exposed to a PEMF. After exposure to antibiotic the pegs were incubated overnight, before standard plating onto blood agar for colony counting. Exposure to a PEMF increased the effectiveness of gentamicin against the five-day biofilms of Staphylococcus epidermidis. In three of five experiments there was reduction of at least 50% in the minimum biofilm inhibitory concentration. In a fourth experiment there was a two-log difference in colony count at 160 mg/l of gentamicin. Analysis of variance (ANOVA) confirmed an effect by a PEMF on the efficacy of gentamicin which was significant at p < 0.05. There was no significant effect with vancomycin

The recently published Prophylactic Antibiotic Regimens In Tumor Surgery (PARITY) trial found no benefit in extending antibiotic prophylaxis from 24 hours to five days after endoprosthetic reconstruction for lower limb bone tumours. PARITY is the first randomized controlled trial in orthopaedic oncology and is a huge step forward in understanding antibiotic prophylaxis. However, significant gaps remain, including questions around antibiotic choice, particularly in the UK, where cephalosporins are avoided due to concerns of Clostridioides difficile infection. We present a review of the evidence for antibiotic choice, dosing, and timing, and a brief description of PARITY, its implication for practice, and the remaining gaps in our understanding.

Cite this article: Bone Joint J 2023;105-B(8):850–856.

Porous blocks of calcium hydroxyapatite ceramic were evaluated as delivery systems for the sustained release of antibiotics. We tested gentamicin sulphate, cefoperazone sodium, and flomoxef sodium in powder form placed in a cylindrical cavity in calcium hydroxyapatite blocks, using in vitro studies of elution and in vivo studies in rats. Gentamicin sulphate gave a maximum concentration within the first week, which gradually decreased but was still effective at 12 weeks, when 70% of the antibiotic had been released. Even at this stage the antibiotic concentration from a 75 mg dose was five times the minimum inhibitory concentration for staphylococci. In the in vivo studies the release of gentamicin sulphate into the normal bone of rats was at similar rates and levels. The bacteriocidal activity of the drugs was not affected by packing into calcium hydroxyapatite ceramic and the blocks were completely biocompatible on histology. This new system overcomes the disadvantages of other drug delivery systems, avoiding thermal damage to the antibiotics and a second operation for the removal of the carrier. Some mechanical strength is provided by the ceramic and healing may be accelerated by bone ingrowth into its micropores

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.

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Gram-negative periprosthetic joint infection (PJI) has been poorly studied despite its rapidly increasing incidence. Treatment with one-stage revision using intra-articular (IA) infusion of antibiotics may offer a reasonable alternative with a distinct advantage of providing a means of delivering the drug in high concentrations. Carbapenems are regarded as the last line of defense against severe Gram-negative or polymicrobial infection. This study presents the results of one-stage revision using intra-articular carbapenem infusion for treating Gram-negative PJI, and analyzes the characteristics of bacteria distribution and drug sensitivity.

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This study was designed to characterize the recurrence incidence and risk factors of antibiotic-loaded cement spacer (ALCS) for definitive bone defect treatment in limb osteomyelitis.

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Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models.

The December 2023 Hip & Pelvis Roundup³⁶⁰ looks at: Early hip fracture surgery is safe for patients on direct oral anticoagulants; Time to return to work by occupational class after total hip or knee arthroplasty; Is there a consensus on air travel following hip and knee arthroplasty?; Predicting whether patients will achieve minimal clinically important differences following hip or knee arthroplasty; High-dose dual-antibiotic-loaded cement for hip hemiarthroplasty in the UK (WHiTE 8): a randomized controlled trial; Vitamin E – a positive thing in your poly?; Hydroxapatite-coated femoral stems: is there a difference in fixation?

Allograft bone is widely used in orthopaedic surgery, but peri-operative infection of the graft remains a common and disastrous complication. The efficacy of systemic prophylactic antibiotics is unproven, and since the graft is avascular it is likely that levels of antibiotic in the graft are low. Using an electrical potential to accelerate diffusion of antibiotics into allograft bone, high levels were achieved in specimens of both sheep and human allograft. In human bone these ranged from 187.1 mg/kg in endosteal (. sd. 15.7) to 124.6 (. sd. 46.2) in periosteal bone for gentamicin and 31.9 (. sd. 8.9) in endosteal and 2.9 (. sd. 1.1) in periosteal bone for flucloxacillin. The antibiotics remained active against bacteria in vitro after iontophoresis and continued to elute from the allograft for up to two weeks. Structural allograft can be supplemented directly with antibiotics using iontophoresis. The technique is simple and inexpensive and offers a potential means of reducing the rate of peri-operative infection in allograft surgery. Iontophoresis into allograft bone may also be applicable to other therapeutic compounds

Aims

The duration of systemic antibiotic treatment following first-stage revision surgery for periprosthetic joint infection (PJI) after total hip arthroplasty (THA) is contentious. Our philosophy is to perform an aggressive debridement, and to use a high local concentration of targeted antibiotics in cement beads and systemic prophylactic antibiotics alone. The aim of this study was to assess the success of this philosophy in the management of PJI of the hip using our two-stage protocol.

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The aim of this investigation was to compare risk of infection in both cemented and uncemented hemiarthroplasty (HA) as well as in total hip arthroplasty (THA) following femoral neck fracture.

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Calcaneal osteomyelitis remains a difficult condition to treat with high rates of recurrence and below-knee amputation, particularly in the presence of severe soft-tissue destruction. This study assesses the outcomes of single-stage orthoplastic surgical treatment of calcaneal osteomyelitis with large soft-tissue defects.

Aims

This study aimed to evaluate the effectiveness of the induced membrane technique for treating infected bone defects, and to explore the factors that might affect patient outcomes.

The diffusion of Fucidin, gentamicin, and clindamycin from acrylic cement was tested in an in vitro system. The activity of Fucidin was very short-lived and only against gram-positive organisms; gentamicin inhibited gram-positive and gram-negative organisms for twenty-two and eleven days respectively; clindamycin had significant action only against gram-positive organisms and retained some activity for fifty-six days. We suggest that the destruction of organisms in the tissues is more likely to be achieved by topical and intravenous administration of antibiotics during the operation than by incorporation of antibiotic in the cement

Aims

Dislocation remains a leading cause of failure following revision total hip arthroplasty (THA). While dual-mobility (DM) bearings have been shown to mitigate this risk, options are limited when retaining or implanting an uncemented shell without modular DM options. In these circumstances, a monoblock DM cup, designed for cementing, can be cemented into an uncemented acetabular shell. The goal of this study was to describe the implant survival, complications, and radiological outcomes of this construct.

Aims

Histology is widely used for diagnosis of persistent infection during reimplantation in two-stage revision hip and knee arthroplasty, although data on its utility remain scarce. Therefore, this study aims to assess the predictive value of permanent sections at reimplantation in relation to reinfection risk, and to compare results of permanent and frozen sections.

Aims

The aim of this retrospective study was to assess the incidence of early periprosthetic femoral fracture (PFF) associated with Charnley-Kerboull (CK) femoral components cemented according to the ‘French paradox’ principles through the Hueter anterior approach (HAA) in patients older than 70 years.

Periprosthetic joint infection (PJI) represents a complex challenge in orthopaedic surgery associated with substantial morbidity and healthcare expenditures. The debridement, antibiotics, and implant retention (DAIR) protocol is a viable treatment, offering several advantages over exchange arthroplasty. With the evolution of treatment strategies, considerable efforts have been directed towards enhancing the efficacy of DAIR, including the development of a phased debridement protocol for acute PJI management. This article provides an in-depth analysis of DAIR, presenting the outcomes of single-stage, two-stage, and repeated DAIR procedures. It delves into the challenges faced, including patient heterogeneity, pathogen identification, variability in surgical techniques, and antibiotics selection. Moreover, critical factors that influence the decision-making process between single- and two-stage DAIR protocols are addressed, including team composition, timing of the intervention, antibiotic regimens, and both anatomical and implant-related considerations. By providing a comprehensive overview of DAIR protocols and their clinical implications, this annotation aims to elucidate the advancements, challenges, and potential future directions in the application of DAIR for PJI management. It is intended to equip clinicians with the insights required to effectively navigate the complexities of implementing DAIR strategies, thereby facilitating informed decision-making for optimizing patient outcomes.

Cite this article: Bone Joint J 2024;106-B(12):1377–1384.

We have developed a new drug-delivery system using reconstituted bone xenograft to treat chronic osteomyelitis. This material, which has the capabilities of osteoinduction and osteoconduction, was supplemented with up to 2000 times the minimum inhibitory concentration of gentamicin against Staphylococcus aureus to prepare a gentamicin-reconstituted bone xenograft-composite (G-RBX-C). In a rabbit model, we evaluated the release of gentamicin from this composite in vivo, its capability for induction of ectopic bone and the repair of segmental defects of the radius. There was a high level of concentration of antibiotics, which was sustained for at least ten days. In the study of induction of ectopic bone, there was abundant woven bone in the G-RBX-C group two weeks after operation. At 16 weeks after implantation of G-RBX-C the radial defects had been repaired, with the formation of lamellar bone and recanalisation of the marrow cavity. Our findings suggest that G-RBX-C may be useful in the treatment of chronic osteomyelitis

Aims

This study aimed to assess the carbon footprint associated with total hip arthroplasty (THA) in a UK hospital setting, considering various components within the operating theatre. The primary objective was to identify actionable areas for reducing carbon emissions and promoting sustainable orthopaedic practices.

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To identify the incidence and risk factors for five-year same-site recurrent disc herniation (sRDH) after primary single-level lumbar discectomy. Secondary outcome was the incidence and risk factors for five-year sRDH reoperation.

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The standard of wide tumour-like resection for chronic osteomyelitis (COM) has been challenged recently by adequate debridement. This paper reviews the evolution of surgical debridement for long bone COM, and presents the outcome of adequate debridement in a tertiary bone infection unit.

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Although low-intensity pulsed ultrasound (LIPUS) combined with disinfectants has been shown to effectively eliminate portions of biofilm in vitro, its efficacy in vivo remains uncertain. Our objective was to assess the antibiofilm potential and safety of LIPUS combined with 0.35% povidone-iodine (PI) in a rat debridement, antibiotics, and implant retention (DAIR) model of periprosthetic joint infection (PJI).

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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.

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We aimed to determine the concentrations of synovial vancomycin and meropenem in patients treated by single-stage revision combined with intra-articular infusion following periprosthetic joint infection (PJI), thereby validating this drug delivery approach.

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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

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.

The release of gentamicin sulphate, sodium fusidate and diethanolamine fusidate from Palacos and CMW cements was studied using elution and serial plate transfer tests. Further tests were made to assay the drug remaining in the cement after antibacterial activity could no longer be detected by the above methods, to detect the sustained slow release of the residual drug, and to ascertain the mechanism of release. The results confirmed that the release of gentamicin sulphate could be detected for longer from Palacos cement than from CMW cement, but the opposite was true for sodium fusidate. Little difference was found in the case of diethanolamine fusidate. Comparison of elution and serial plate transfer tests, and of results of elution in buffers of different pH, demonstrated that the test method employed had a significant effect on the results, and the omission of details of methodology from some publications made comparison and evaluation of results difficult. Varying quantities of residual drug were found in cement from which antibacterial activity could no longer be demonstrated; further tests for sustained, slow release showed that the antibiotic did not remain fixed in the cement but was released at a rate too slow to be detected in the elution and serial plate transfer tests. It is concluded that antibiotics are released from the cement by a process of diffusion, but tests to determine the mechanism of diffusion were unhelpful. The theory of diffusion of drugs through solid matrices, and the clinical implications of the experimental findings, are discussed

Aims

Bone regeneration during treatment of staphylococcal bone infection is challenging due to the ability of Staphylococcus aureus to invade and persist within osteoblasts. Here, we sought to determine whether the metabolic and extracellular organic matrix formation and mineralization ability of S. aureus-infected human osteoblasts can be restored after rifampicin (RMP) therapy.

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The aim of the HIPGEN consortium is to develop the first cell therapy product for hip fracture patients using PLacental-eXpanded (PLX-PAD) stromal cells.

The Morscher-Spotorno (MS-30) femoral stem is a stainless-steel, straight, three-dimensionally tapered, collarless implant for cemented fixation in total hip replacement. We report the results at ten years of a consecutive series of 124 total hip replacements in 121 patients with the matt-surfaced MS-30 stem and an alumina ceramic head of 28-mm diameter. All the stems were fixed with Palacos bone cement with gentamicin using a modern cementing technique. They were combined with an uncemented, press-fit cup. The mean period of observation was 10.2 years (8.3 to 12.1) and no patient was lost to follow-up. Twenty-seven patients (22%) died with the implant in situ. Nine could only be interviewed by telephone. We included 85 patients with 88 hips in the clinical and radiological follow-up examinations. None of the stems or cups had been revised. The Harris hip score was excellent or good in 97% (85 hips) and moderate in 3% (three hips). Radiologically, six hips (6.8%) had osteolysis adjacent to the stem, mostly in Gruen zone 7. Twenty (22.7%) showed one or more radiolucent lines. Twenty-two stems (25%) had subsided by 2 mm to 5 mm. In these cases two showed osteolysis (9.1%) with subsidence and four without (6.1%). Radiolucent lines were seen in seven with migration (31.8%) and in 13 without (19.7%). No infections and no acetabular osteolysis were observed. The clinical results were excellent with survivorship after ten years of 100% and only a slightly statistically non-significant higher rate of osteolysis and radiolucency in cases of subsidence

Aims

To establish our early clinical results of a new total knee arthroplasty (TKA) tibial component introduced in 2013 and compare it to other designs in use at our hospital during the same period.

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In contrast to operations performed for other fractures, there is a high incidence rate of surgical site infection (SSI) post-open reduction and internal fixation (ORIF) done for tibial plateau fractures (TPFs). This study investigates the effect of induced membrane technique combined with internal fixation for managing SSI in TPF patients who underwent ORIF.

Aims

Fungal and mycobacterial periprosthetic joint infections (PJI) are rare events. Clinicians are wary of missing these diagnoses, often leading to the routine ordering of fungal and mycobacterial cultures on periprosthetic specimens. Our goal was to examine the utility of these cultures and explore a modern bacterial culture technique using bacterial blood culture bottles (BCBs) as an alternative.

Aims

The management of periprosthetic joint infection (PJI) after total knee arthroplasty (TKA) is challenging. The correct antibiotic management remains elusive due to differences in epidemiology and resistance between countries, and reports in the literature. Before the efficacy of surgical treatment is investigated, it is crucial to analyze the bacterial strains causing PJI, especially for patients in whom no organisms are grown.

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.

Aims

Fungal periprosthetic joint infections (fPJIs) are rare complications, constituting only 1% of all PJIs. Neither a uniform definition for fPJI has been established, nor a standardized treatment regimen. Compared to bacterial PJI, there is little evidence for fPJI in the literature with divergent results. Hence, we implemented a novel treatment algorithm based on three-stage revision arthroplasty, with local and systemic antifungal therapy to optimize treatment for fPJI.

Aims

The use and variety of stemless humeral components in anatomical total shoulder arthroplasty (TSA) have proliferated since their advent in 2004. Early outcomes are reassuring but independent mid-term results are scarce. This independent study reports a consecutive series of 143 Eclipse stemless shoulder prostheses with a minimum five-year (5 to 10) follow-up.

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

One-stage revision hip arthroplasty for periprosthetic joint infection (PJI) has several advantages; however, resection of the proximal femur might be necessary to achieve higher success rates. We investigated the risk factors for resection and re-revisions, and assessed complications and subsequent re-revisions.

Aims

In our unit, we adopt a two-stage surgical reconstruction approach using internal fixation for the management of infected Charcot foot deformity. We evaluate our experience with this functional limb salvage method.

We have compared the rates of infection and resistance in an animal model of an orthopaedic procedure which was contaminated with a low-dose inoculum of Staphylococcus epidermidis. We randomised 44 Sprague-Dawley rats to have bone cement implanted subcutaneously containing either gentamicin or saline (control). The wound was inoculated with a dilute solution of gentamicin-sensitive Staphylococcus epidermidis. At two weeks the cement was retrieved and microbiologically tested. A lower overall rate of infection was seen in the gentamicin-loaded cement group, but there was a significantly higher rate of gentamicin-resistant infection in this group (Fisher’s exact test, p < 0.01). Antibiotic-impregnated cement has an optimum surface for colonisation and prolonged exposure to antibiotic allows mutational resistance to occur. Gentamicin-loaded cement may not be appropriate for revision surgery if it has been used already in previous surgery

An experimental evaluation was made of the efficacy of an unflanged cup, an ogee-flanged cup and the Exeter pressuriser in the pressurisation of acetabular cement. Only a very modest injection pressure could be generated through an unflanged socket and even this was readily lost as the socket "bottomed out". The ogee-flanged socket gave a consistently high injection pressure which could be maintained throughout the process of polymerisation. The Exeter pressuriser gave marginally better results. Of the two cements tested, Palacos with gentamicin showed better intrusion than CMW Type 1 cement, but it also allowed greater extrusion once pressure was released. The importance of maintaining a continuous pressure on the cement throughout polymerisation is emphasised

Aims

Biofilm formation is one of the primary reasons for the difficulty in treating implant-related infections (IRIs). Focused high-energy extracorporeal shockwave therapy (fhESWT), which is a treatment modality for fracture nonunions, has been shown to have a direct antibacterial effect on planktonic bacteria. The goal of the present study was to investigate the effect of fhESWT on Staphylococcus aureus biofilms in vitro in the presence and absence of antibiotic agents.

Aims

It remains difficult to diagnose early postoperative periprosthetic joint infection (PJI) following total knee arthroplasty (TKA). We aimed to validate the optimal cutoff values of ESR, CRP, and synovial fluid analysis for detecting early postoperative PJI in a large series of primary TKAs.

In thirty-one rat tibiae, plugs of plain acrylic cement were inoculated with Staphylococcus aureus; these all remained contaminated at the end of two weeks when the animals were killed. Inoculation with known strains of Pseudomonas, Proteus and Gp. G Streptococcus resulted in 70 to 93 per cent persisting contamination. Gentamicin, to which the organisms were fully sensitive, was efficacious in controlling the infection (90 per cent plugs proving sterile after two weeks). Fucidin was less successful against Staphylococcus aureus although effective in vitro. Intravenous inoculation with a suspension of Staphylococcus aureus succeeded in contaminanting 70 per cent of sixty plain cement plugs when injected into the tail vein half an hour after closure of the leg wounds. Only 11 per cent of sixty-four plugs were so contaminanted when the injection was delayed for two weeks. This animal model is submitted as a possible future means of testing different antibiotic-cement combinations against infection

Aims

This study presents patient-reported quality of life (QoL) over the first year following surgical debridement of long bone osteomyelitis. It assesses the bone involvement, antimicrobial options, coverage of soft tissues, and host status (BACH) classification as a prognostic tool and its ability to stratify cases into ‘uncomplicated’ or ‘complex’.

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

Bone stock restoration of acetabular bone defects using impaction bone grafting (IBG) in total hip arthroplasty may facilitate future re-revision in the event of failure of the reconstruction. We hypothesized that the acetabular bone defect during re-revision surgery after IBG was smaller than during the previous revision surgery. The clinical and radiological results of re-revisions with repeated use of IBG were also analyzed.

Aims

Treatment of chronic osteomyelitis (COM) for young patients remains a challenge. Large bone deficiencies secondary to COM can be treated using induced membrane technique (IMT). However, it is unclear which type of bone graft is optimal. The goal of the study was to determine the clinical effectiveness of bone marrow concentrator modified allograft (BMCA) versus bone marrow aspirate mixed allograft (BMAA) for children with COM of long bones.

Aims

Extracellular matrix (ECM) and its architecture have a vital role in articular cartilage (AC) structure and function. We hypothesized that a multi-layered chitosan-gelatin (CG) scaffold that resembles ECM, as well as native collagen architecture of AC, will achieve superior chondrogenesis and AC regeneration. We also compared its in vitro and in vivo outcomes with randomly aligned CG scaffold.

Aims

Flucloxacillin is commonly administered intravenously for perioperative antimicrobial prophylaxis, while oral administration is typical for prophylaxis following smaller traumatic wounds. We assessed the time, for which the free flucloxacillin concentration was maintained above the minimum inhibitory concentration (fT > MIC) for methicillin-susceptible Staphylococcus aureus in soft and bone tissue, after intravenous and oral administration, using microdialysis in a porcine model.

Aims

Metaphyseal fixation during revision total knee arthroplasty (TKA) is important, but potentially difficult when using historical designs of cone. Material and manufacturing innovations have improved the size and shape of the cones which are available, and simplified the required bone preparation. In a large series, we assessed the implant survivorship, radiological results, and clinical outcomes of new porous 3D-printed titanium metaphyseal cones featuring a reamer-based system.

Implant-related infection is one of the leading reasons for failure in orthopaedics and trauma, and results in high social and economic costs. Various antibacterial coating technologies have proven to be safe and effective both in preclinical and clinical studies, with post-surgical implant-related infections reduced by 90% in some cases, depending on the type of coating and experimental setup used. Economic assessment may enable the cost-to-benefit profile of any given antibacterial coating to be defined, based on the expected infection rate with and without the coating, the cost of the infection management, and the cost of the coating. After reviewing the latest evidence on the available antibacterial coatings, we quantified the impact caused by delaying their large-scale application. Considering only joint arthroplasties, our calculations indicated that for an antibacterial coating, with a final user’s cost price of €600 and able to reduce post-surgical infection by 80%, each year of delay to its large-scale application would cause an estimated 35 200 new cases of post-surgical infection in Europe, equating to additional hospital costs of approximately €440 million per year. An adequate reimbursement policy for antibacterial coatings may benefit patients, healthcare systems, and related research, as could faster and more affordable regulatory pathways for the technologies still in the pipeline. This could significantly reduce the social and economic burden of implant-related infections in orthopaedics and trauma.

Cite this article: C. L. Romanò, H. Tsuchiya, I. Morelli, A. G. Battaglia, L. Drago. Antibacterial coating of implants: are we missing something? Bone Joint Res 2019;8:199–206. DOI: 10.1302/2046-3758.85.BJR-2018-0316.

Aims

Total knee arthroplasty is an established treatment for knee osteoarthritis with excellent long-term results, but there remains controversy about the role of uncemented prostheses. We present the long-term results of a randomized trial comparing an uncemented tantalum metal tibial component with a conventional cemented component of the same implant design.

Aims

The aim of this study was to investigate whether the use of antibiotic-loaded bone cement influenced the risk of revision surgery after primary total hip arthroplasty (THA) for osteoarthritis.

Objectives

Preclinical data showed poly(methyl methacrylate) (PMMA) loaded with microsilver to be effective against a variety of bacteria. The purpose of this study was to assess patient safety of PMMA spacers with microsilver in prosthetic hip infections in a prospective cohort study.

Aims

Local antibiotics are used in the surgical management of foot infection in diabetic patients. This systematic review analyzes the available evidence of the use of local antibiotic delivery systems as an adjunct to surgery.

Aims

This study aimed to determine if macrophages can attach and directly affect the oxide layers of 316L stainless steel, titanium alloy (Ti6Al4V), and cobalt-chromium-molybdenum alloy (CoCrMo) by releasing components of these alloys.

Objectives

The objective of this study was to characterize the effect of rifampin incorporation into poly(methyl methacrylate) (PMMA) bone cement. While incompatibilities between the two materials have been previously noted, we sought to identify and quantify the cause of rifampin’s effects, including alterations in curing properties, mechanical strength, and residual monomer content.

Aims

Arthrodesis is rarely used as a salvage procedure for patients with a chronically infected total knee arthroplasty (TKA), and little information is available about the outcome. The aim of this study was to assess the reliability, durability, and safety of this procedure as the definitive treatment for complex, chronically infected TKA, in a current series of patients.

Objectives

Prosthetic joint infection (PJI) is the most common cause of arthroplasty failure. However, infection is often difficult to detect by conventional bacterial cultures, for which false-negative rates are 23% to 35%. In contrast, 16S rRNA metagenomics has been shown to quantitatively detect unculturable, unsuspected, and unviable pathogens. In this study, we investigated the use of 16S rRNA metagenomics for detection of bacterial pathogens in synovial fluid (SF) from patients with hip or knee PJI.