Background. In the UK, over 160,000 total joint replacements are performed annually. About 1% of patients subsequently develop a deep bacterial infection and, if untreated, this can result in severe pain, disability, and death. Costs to the NHS are substantial. The INFORM (Infection Orthopaedic Management) programme aims to address gaps in knowledge relating to treatment of deep prosthetic joint infection through six work packages. The programme is supported by a patient forum and patient-partners working on oversight groups. Methods. Literature reviews and meta-analysis of individual patient data from cohort studies of patients treated for prosthetic hip infection. Analysis of the National Joint Registry to observe trends in infection rates, and identify risk markers for infection and effective treatments. Qualitative interviews with patients and health professionals exploring the impact of infection and its treatment. A multicentre randomised controlled trial to compare patient-centred outcomes after one- or two-stage revision for prosthetic hip infection. An economic evaluation to assess cost-effectiveness of treatments. A survey of patients to explore individuals’ preferences for treatments. Results. Individual patient data has been provided by UK and international centres. Data on over 1.4 million procedures is available from the National Joint Registry. Interviews conducted with 19 patients with prosthetic hip infection and 12 treating surgeons. Information has advised randomised controlled trial methodology. Seven major UK centres recruiting patients to the INFORM randomised controlled trial. Methods for assessment of costs from a health service and societal perspective developed for the randomised controlled trial. Qualitative studies have contributed to the design of a discrete choice questionnaire. Conclusions. Findings from INFORM will establish how patient care and outcomes can be optimised after prosthetic joint infection. Guidance on best clinical practice will be developed. Level of evidence 1–3. Funding statement This abstract presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (grant number: RP-PG-1210-12005). The views expressed in this abstract are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health

Deep infection represents one of the most devastating complications of total knee arthroplasty. Commonly implicated organisms are gram positive bacteria such as staphylococcus aureus, staphylococcus epidermidis and group B streptococcus. Occasionally, infection may be caused by rare organisms, particularly in the immunocompromised host. We present a case of infected total knee arthroplasty in a penicillin allergic patient, caused by Pasteurella multocida, 13 weeks after the initial surgery. This was treated by open debridement and change of insert as well as aggressive antibiotic therapy. The patient admitted contact with a cat and three dogs at home. Pasteurella multocida is a facultatively anaerobic gram negative coccobacillus. It is a commensal in the nasopharygeal tract of domestic pets such as cats and dogs. Human infection can often be attributed to a bite or scratch. Prosthetic joint infection caused by Pasteurella is uncommon. Only a few cases have been reported in the literature. Our case has several learning points: (1) It is very important to definitively identify Pasteurella because standard therapy for prosthetic joint infection (e.g. flucloxacillin or vancomycin) is not optimal for this species.(2) Pasteurella are susceptible to penicillin, but the optimal antibiotic therapy for infections in patients allergic to beta lactam antibiotics is uncertain. A combination of ciprofloxacin and linezolid is recommended. (3) There is no consensus regarding appropriate management. There are reports of washout and antibiotic therapy alone, single and two stage revision procedures. In our case, at five months follow up, open debridement and change of insert along with antibiotic treatment appears to have been effective, although more long term follow up is required. (4)Post arthroplasty, all patients with pets at home should be advised to seek medical attention following any bite or scratch so that timely prophylaxis can be administered before sepsis becomes deep-seated

Background. Smoking has been associated with poor tissue oxygenation and vascularisation, predisposing smokers to a higher risk for postsurgical infections. The aim of this study was to estimate and compare the incidence of prosthetic joint infection (PJI) following primary total joint arthroplasty (TJA) according to smoking status. Methods. A prospective hospital-registry based cohort was used including all primary total knee and hip arthroplasties performed between 03/1996 and 12/2013 and following them until 06/2014. Smoking status at time of surgery was classified in never, former and current smoker. Incidence rates and incidence rate ratios (IRR) for PJI according to smoking status were assessed within the first year and over the whole study period. Adjusted IRRs were obtained using cox regression model. Adjustment was performed for the following baseline characteristics: age, sex, BMI, ASA score, diabetes, arthroplasty site (knee or hip) and surgery duration. Results. We included 8,559 TJAs, 3,361 knee and 5,198 hip arthroplasties. Mean age was 70 years, 61% were women, mean follow-up time was 77 months. 5,722 were never (group 1), 1,315 former (group 2) and 1,522 current (group 3) smokers. Over the study period, 108 PJI occurred. Incidence rates of infection within one year were for group 1, 2 and 3, respectively: 4.7, 10.1 and 10.9 cases/1000 person-year. Comparing ever- vs. never-smokers, the adjusted IRR was 1.84 (95% CI 1.05–3.2). Incidence rates for infection over the whole study period were 1.5, 3.1 and 2.7 cases/1000 person-years for group 1, 2 and 3, respectively. Adjusted IRR for ever- vs. never-smokers was 1.46 (95% CI 0.97–2.19). Conclusions. Smoking was associated with an about 1.5 times higher incidence rate of PJI following TJA. The difference was established already in the first year after surgery and remained thereafter. Level of Evidence. prospective registry based comparative cohort study (level II)

In a new rabbit model of carbapenem-resistant Klebsiella pneumoniae knee-prosthesis infection, we studied the efficacy of colistin cement alone or in combination with systemic intramuscular (i.m.) injections of colistin. Seven days after infection, surgical debridement and removal of the infected prostheses were performed, and rabbits were randomly assigned to one of four different treatment groups of twelve rabbits: prosthesis replacement by drug-free cement spacer (control) prosthesis replacement by colistin-loaded cement spacer (3 MUI of colistin/40 g of cement) (colistin local), prosthesis replacement by drug-free cement spacer and i.m. colistin (12 mg/kg of body weight, three time a day for 7 days), or colistin local + i.m. We observed a statistically significant difference (p = 0.049) between the colistin local + systemic group and the control group in the criteria of number of rabbits with sterile bone under the total number of rabbits. Combination of systemic and local colistin could be an interesting therapeutic option to cure carbapenem-resistant Klebsiella pneumoniae peri prosthetic joint infection

Around 1% of total hip replacements are follow by prosthetic joint infection (PJI). There is uncertainty about best treatment method for PJI, and the most recent high quality systematic reviews in unselected patients indicates that re-infection rates following one-stage and two-stage revision arthroplasty are relatively similar. In the absence of evidence randomised controlled trials will help to identify the most clinically and cost-effective treatment for PJI. Before such trials are conducted, there is a need to establish reasons for current practice and to identify whether trials are feasible. This study aimed to deliver research that would inform trial design. Specifically, we aimed to characterise consultant orthopaedic surgeons' decisions about performing either one-stage or two-stage exchange arthroplasty for patients with PJI after hip replacement and to identify whether a randomised trial comparing one-stage with two-stage revision would be possible. Semi-structured interviews were conducted with 12 consultant surgeons from 5 high-volume National Health Service (NHS) orthopaedic departments in the UK. Surgeons were sampled on the basis that they perform revision surgery for PJI after hip arthroplasty and final sample size was justified on the basis of thematic saturation. Surgeons were interviewed face-to-face (n=2) or via telephone (n=10). The interview study took place before design of a multicentre prospective randomised controlled trial comparing patient and clinical outcomes after one-stage or two-stage revision arthroplasty. Data were audio-recorded, transcribed, anonymised and analysed using a thematic approach, with 25% of transcripts independently double-coded. Results: There is no standard surgical response to the treatment of PJI and surgeons manage a complex balance of factors when choosing a surgical strategy. These include multiple patient-related factors, their own knowledge and expertise, available infrastructure and the infecting organism. Surgeons questioned whether evidence supports the emergence of two-stage revision as a method. They described the use of loosely cemented articulating spacers as a way of managing uncertainty about best treatment method. All surgeons were supportive of a randomised trial to compare one-stage and two-stage revision surgery for PJI after hip replacement. Surgeons reported that they would put patients forward for randomisation when there was uncertainty about best treatment. Surgeons highlighted the need for evidence to support their choice of revision. Some surgeons now use revision methods that can better address both clinical outcomes and patients' quality of life, such as loosely cemented articulating spacers. Surgeons thought that a randomised controlled trial comparing one-stage and two-stage exchange joint replacement is needed and that randomisation would be feasible. The next stage of the work was to design a multi-centre randomised controlled trial, this has been achieved and the trial is now ongoing in the UK

Around 1% of the 185,000 primary hip and knee arthroplasties performed in the UK are followed by prosthetic joint infection (PJI). Although PJI affects a small percentage of patients, it is one of the most devastating complications associated with this procedure. Treatment usually involves further major surgery which can adversely affect patients' quality of life. Understanding current service provision provides valuable information needed to design and evaluate support interventions for patients. The aim of this survey was to identify usual care pathways and support in UK NHS orthopaedic centres for this population. The 20 highestvolume UK NHS orthopaedic centresfor hip and knee arthroplasty account for 33–50% of all cases treated for prosthetic joint infection. Infection leads at each centre were invited to participate in a survey about usual care provision and support for PJI. Questions exploredfollow up time-points; use of standard outcome measures; multidisciplinary care plans; supportive in-patient care and care after treatment; and onward referrals. Survey responses were recorded on a standardised proforma. Data were entered into Excel for analysis, then reviewed and coded into categories and frequency statistics to describe categorical data. A descriptive summary was developed based on these categories. Eleven of the highestvolume orthopaedic centres completed the survey. Follow-up of patients varied greatly across centres; some centres reviewed patients at weekly or 2 week intervals, while all centres saw patients at 6 weeks. Long-term follow-up varied across centres from 3–4 monthsto 12 monthly. Length of follow-up period varied from until the infection had cleared toindefinitely. Follow-up timepoints were only standardised in 4 out of 11 centres. Only 1 centre had a dedicated infection clinic. Advice on who patients should contact if they had concerns included the consultant, community nurse, extended scope practitioner or the ward, while 3 centres told patients to avoid calling their GP. Only half of the centres routinely used standardised outcome measures with patients with PJI. The majority of centres provided standard physiotherapy and occupational therapy (OT) to in-patients while approximately half also offered social support. Only one centre provided dedicated physiotherapy and OT on a separate infection ward. Three centres provided hospital at home or community services to patients in-between operative stages. Only 3 out of 11 centres stated they had specific multidisciplinary care plans in place for patients. Once discharged most patients were provided with physiotherapy, OT and social services if needed. Common barriersto referral included complexities of referring patients outside the hospital catchment area;lack of availability of community services, and shortage of staff including physiotherapists. Delays in rehab and social services could also be problematic. Findings show wide variation intreatment pathways and support for patients treated for PJI, both as inpatients and in the community. Only one of the 11 centreswho participated had a dedicated infection clinic. Only one centre suggested they individualised their physiotherapy support. A number of barriers exist to referring patients on to other support services after revision surgery

Introduction. Prosthetic joint infection (PJI) is an uncommon but serious complication of hip replacement. A recent systematic review of patient risk factors for PJI identified male gender, smoking status, increasing BMI, steroid use, previous joint surgery and comorbidities of diabetes, rheumatoid arthritis and depression as risk factors for developing PJI. Limitations of the current literature include the short term follow up of most published studies. We investigated the role of patient, surgical and healthcare factors on the risk of revision of a primary hip replacement for PJI at different time-points in the post-operative follow-up. It is important that those risk factors are identified so that patients can be appropriately counselled according to their individual risk profile prior to surgery and modifiable factors can be addressed to reduce the risk of PJI at an individual and healthcare system level. Materials and Methods. Primary hip replacements and subsequent revision procedures performed for PJI from 2003–2014 were identified from the National Joint Registry (NJR). Patient (age, gender, ASA grade, BMI), perioperative (surgical indication, type of anaesthesia, thromboprophylaxis regime, surgical approach, hip replacement and bearing surface and use of femoral or acetabular bone graft) and healthcare system characteristics (surgeon grade, surgical volume) were linked with data from Hospital Episode Statistics to obtain information on specific ethnicity and comorbidities (derived from the Charlson index). Multilevel piecewise exponential non-proportional hazards models were used to estimate their effects at different post-operative periods (0–3 months, 3–6 months, 6–12 months, 12–24 and >24 months post-operation). Results. The index hip replacements consisted of 623,253 primaries with 2,705 subsequently revised for PJI, 14% within 3 months, 8% between 3–6 months, 14% between 6–12 months, 22% between 1–2 years and 42% ≥2 years after the index procedure. Risk factors for revision of PJI included male gender, high BMI, high ASA grade and younger age. Their effects were period-specific. Patients with chronic pulmonary disease, diabetes or dementia had high early risk of revision for PJI, as did patients operated for a fractured neck of femur (<3 months). Metal-on-metal bearings (>12 months) and lateral surgical approach (≥3 months) also influenced the mid- and long-term revision risk for PJI. No or modest associations were found with the operating surgeon grade, surgical volume and hospital surgical volume. Conclusion. The effects of patient, perioperative and healthcare system risk factors for PJI after primary hip replacement are time-dependent. Modifiable risk factors such as the type of surgical approach and bearing surface have also been found

Joint arthroplasty is a common surgical procedure, with over 185,000 primary hip and knee arthroplasties performed in England, Wales and Northern Ireland in 2014. After total hip or knee arthroplasty, about 1% of patients develop deep prosthetic joint infection (PJI), which usually requires further major operations to clear the infection. Although PJI affects only a small percentage of patients it is one of the most devastating complications associated with this procedure. Research evidence has focussed on clinical effectiveness of revision surgery while there has been less focus on the impact on patients and support needs. Using a systematic review approach, the aim of this study was to assess support needs and evaluate what interventions are routinely offered to support patients undergoing treatment for PJI following hip or knee arthroplasty. We systematically searched MEDLINE, Embase, Web of Science, PsycINFO, Cinahl, Social Science Citation Index, and The Cochrane Library from 1980 to February 15, 2015 for observational (prospective cohort, nested case-control, case-control, and retrospective cohort) studies, qualitative studies, and clinical trials that report on the support needs and interventions for patients being treated for PJI or other major adverse occurrences following joint arthroplasty. Data were extracted by two independent investigators and consensus reached with involvement of a third. Of 4,161 potentially relevant citations, we identified one case-control, one prospective cohort and two qualitative studies for inclusion in the synthesis. Patients report that PJI and treatment had a profoundly negative impact affecting physical, emotional, social and economic aspects of their lives. No study evaluated support interventions for PJI or other major adverse occurrences following hip and knee arthroplasty. The interpretation of study results is limited by variation in study design, outcome measures and the small number of relevant eligible studies. Findings show that patients undergoing treatment for PJI have extensive physical, psychological, social and economic support needs. Our review highlights a lack of evidence about support strategies for patients undergoing treatment for PJI and other adverse occurrences. There is a need to design, implement and evaluate interventions to support these patients

Periprosthetic joint infections (PJIs) are uncommon but are devastating complications of total knee replacement (TKR). We analysed the risk factors of revision for PJI following primary TKR and their association with PJI at different post-operative periods. Primary TKRs and subsequent revision surgeries performed for PJI from 2003–2014 were identified from the National Joint Registry (NJR). Multilevel piece-wise exponential non-proportional hazards models were used to estimate the effect of the investigated factors at different post-operative periods. Patient, perioperative and healthcare system characteristics were investigated and data from the Hospital Episode Statistics for England were linked to obtain information on specific comorbidities. The index TKRs consisted of 679,010 primaries with 3,659 subsequently revised for PJI, 7% within 3 months, 6% between 3–6months, 17% between 6–12months, 27% between 1–2years and 43% ≥2 years from the index procedure. Risk factors for revision for PJI included male sex, high BMI, high ASA grade and young age. Patients with chronic pulmonary disease, diabetes and liver disease had higher risk of revision for PJI, as had patients who had a primary TKR for an indication of trauma or inflammatory arthropathy. Surgical procedure, fixation method, constraint and bearing type influenced the risk of revision for PJI. Their effects were period-specific. No or small associations were found with the operating surgeon grade, surgical volume and hospital surgical volume. These findings from the world's largest joint replacement registry show a more complex picture than the meta-analyses published to date with specific time-dependent effects for the identified risk factors.

Prosthetic Joint Infection (PJI) is a devastating complication that can occur after total joint replacement surgery. With increasing antimicrobial resistance, there is a need for non-antibiotic approaches to treat and prevent PJI. Doping calcium phosphates with antimicrobial ions shows promise for these purposes. This systematic review aims to search and summarise the evidence-base for the potential of calcium phosphates doped with different antimicrobial ions. A systematic review was conducted on PubMed, Embase, Web-Of-Science, Cochrane Library and Emcare of in vitro and animal studies on the antimicrobial activity of (co)substituted calcium phosphates according to PRIMSA guidelines.. The research protocol, listing search terms and in/exclusion criteria, was registered a priori at . https://doi.org/10.7910/DVN/HEP18U. Data was extracted regarding ions, micro-organisms and antimicrobial activity. The search retrieved 1017 hits of which 148 papers were included. The substitution of 33 different ions was reported. Silver (n= 46), zinc (n=39), copper (n=18) and magnesium (n=14) were the most commonly doped ions. 36 different micro-organisms were studied of which E. coli (n=109), S. aureus (n=99), and C. albicans (n=22) were the most common. 6 different outcomes were reported, most commonly the K-ratio (n=53), the log CFU (n=41) and the bacterial inhibition zone (n=39). A validated outcome for the evaluation of biofilm prevention was lacking. There was considerable heterogeneity in studied ions, micro-organisms and reported outcomes. A lack of clearly defined reporting guidelines in the field of antimicrobial materials has led to the use of clinically irrelevant micro-organisms and a general lack of consistency of the methods used and the reported results. Currently, there is no universally accepted measure for the effectiveness required from biomaterials for treatment and prevention of PJI

Prosthetic joint infection (PJI) is an important cause of arthroplasty failure. There is no method to disclose the presence or map the distribution of the in vivo biofilm on infected arthroplasty despite the recognition that such a tool would aid intraoperative decision making and improve novel implant design. The aim of this study was to test the efficacy of four dyes to disclose bacterial biofilm in an in vitro setting. Four dyes with known affinity to bacterial biofilm were assessed to determine their efficacy to disclose biofilms in an in vitro model of PJI. Three dyes (Methylene Blue, Indocyanine Green and Rose Bengal) have established clinical utility and the other, Thioflavin T, is known to fluoresce in the presence of amyloid a known biofilm constituent. The efficacy of the dyes to discriminate between biofilms of different mass and vitality (high, low or the non-inoculated control) was determined after three minutes exposure of the biofilm to the dyes by calculating the amount of dye bound to the biofilm via sonication and spectrophotometry, quantification of the dye through standardised photographic imaging of the stained biofilm and the calculation of inter-observer agreement. Each experiment was performed in triplicate for each dye and repeated three times. For each of the disclosure dyes assessed there was significant difference demonstrated between the amount of dye bound to the high and low mass biofilms (p<0.05) as well as in the amount of dye quantified in photographic and fluorescent image assessment between biofilms of differing mass (p<0.01). There was excellent agreement between three observers, for each disclosure dye, in determining the biofilm mass of each stained disc (Kappa>0.91). This study demonstrates the efficacy of biofilm disclosure dyes in an in vitro PJI model which could one day be used to disclose and map the clinical biofilm in vivo

Prosthetic joint infection (PJI) is a serious complication following joint replacement. Antiseptic solutions are often used for intraoperative wound irrigation particularly in cases of revision for PJI. Antiseptic irrigation is intended to eradicate residual bacteria which may be either free floating or in residual biofilm although there is no clear clinical efficacy for its use. Also, reviewing the scientific literature there is discordance in in vitro results where some studies questions antiseptic efficacy whilst others suggest that even at low concentration antiseptic agents are effective at eradicating bacterial biofilms. The aim of this in vitro study was to establish the efficacy of undiluted antiseptic agents at eradication of a typical PJI forming biofilm and determine the importance of an antiseptic neutralisation step in this assessment. Mature Staphylococcus epidermidis biofilms grown on TiAl6V4 discs were submerged in chlorohexidine (CHL) gluconate 4%, povidone-iodine (PI) 10% or phosphate-buffered saline (PBS) control solution. The discs were then rinsed, the biofilm bacteria suspended in solution using sonication and vortexing, and the viable count (CFU/ml) of the bacterial suspensions determined. The rinse/suspension solution was either (a) PBS or (b) Dey-Engley neutralization broth (NB). When PBS was used to rinse/suspend the biofilm a highly significant, 7.5 and 4.1, mean log reduction in biofilm vitality was observed from the control, for CHL 4% and PI 10%, respectively. However, when NB was the rinse/suspension solution the apparent antiseptic biofilm eradication efficacy was replaced with a statistically significant but clinically irrelevant less the one log-reduction in biofilm vitality. Clinical antiseptic agents are ineffective at eradicating S. epidermidis biofilm in an in vitro PJI model and absence of a neutralisation step gives the false impression of efficacy. Antiseptics alone are an ineffective treatment for biofilm related PJI and no substitute for meticulous debridement

Prosthetic joint infections represent complications connected to the implantation of biomedical devices, they have high incidence, interfere with osseointegration, and lead to a high societal burden. The microbial biofilm, which is a complex structure of microbial cells firmly attached to a surface, is one of the main issues causing infections. Biofilm- forming bacteria are acquiring more and more resistances to common clinical treatments due to the abuse of antibiotics administration. Therefore, there is increasing need to develop alternative methods exerting antibacterial activities against multidrug-resistant biofilm-forming bacteria. In this context, metal-based coatings with antimicrobial activities have been investigated and are currently used in the clinical practice. However, traditional coatings exhibit some drawbacks related to the insufficient adhesion to the substrate, scarce uniformity and scarce control over the toxic metal release reducing their efficacy. Here, we propose the use of antimicrobial silver-based nanostructured thin films to discourage bacterial infections. Coatings are obtained by Ionized Jet Deposition, a plasma-assisted technique that permits to manufacture films of submicrometric thickness having a nanostructured surface texture, allow tuning silver release, and avoid delamination. To mitigate interference with osseointegration, here silver composites with bone apatite and hydroxyapatite were explored. The antibacterial efficacy of silver films was tested in vitro against gram- positive and gram-negative species to determine the optimal coatings characteristics by assessing reduction of bacterial viability, adhesion to substrate, and biofilm formation. Efficacy was tested in an in vivo rabbit model, using a multidrug-resistant strain of Staphylococcus aureus showing significant reduction of the bacterial load on the silver prosthesis both when coated with the metal only (>99% reduction) and when in combination with bone apatite (>86% reduction). These studies indicate that IJD films are highly tunable and can be a promising route to overcome the main challenges in orthopedic prostheses

Prosthetic joint infections represent complications connected to the implantation of biomedical devices, they have high incidence, interfere with osseointegration, and lead to a high societal burden. The microbial biofilm, which is a complex structure of microbial cells firmly attached to a surface, is one of the main issues causing infections. Biofilm- forming bacteria are acquiring more and more resistances to common clinical treatments due to the abuse of antibiotics administration. Therefore, there is increasing need to develop alternative methods exerting antibacterial activities against multidrug-resistant biofilm-forming bacteria. In this context, metal-based coatings with antimicrobial activities have been investigated and are currently used in the clinical practice. However, traditional coatings exhibit some drawbacks related to the insufficient adhesion to the substrate, scarce uniformity and scarce control over the toxic metal release reducing their efficacy. Here, we propose the use of antimicrobial silver-based nanostructured thin films to discourage bacterial infections. Coatings are obtained by Ionized Jet Deposition, a plasma-assisted technique that permits to manufacture films of submicrometric thickness having a nanostructured surface texture, allow tuning silver release, and avoid delamination. To mitigate interference with osseointegration, here silver composites with bone apatite and hydroxyapatite were explored. The antibacterial efficacy of silver films was tested in vitro against gram- positive and gram-negative species to determine the optimal coatings characteristics by assessing reduction of bacterial viability, adhesion to substrate, and biofilm formation. Efficacy was tested in an in vivo rabbit model, using a multidrug-resistant strain of Staphylococcus aureus showing significant reduction of the bacterial load on the silver prosthesis both when coated with the metal only (>99% reduction) and when in combination with bone apatite (>86% reduction). These studies indicate that IJD films are highly tunable and can be a promising route to overcome the main challenges in orthopedic prostheses

Prosthetic joint infections represent complications connected to the implantation of biomedical devices. Bacterial biofilm is one of the main issues causing infections from contaminated orthopaedic prostheses. Biofilm is a structured community of microbial cells that are firmly attached to a surface and have unique metabolic and physiological attributes that induce improved resistance to environmental stresses including toxic compounds like antimicrobial molecules (e.g. antibiotics). Therefore, there is increasing need to develop methods/treatments exerting antibacterial activities not only against planktonic (suspended) cells but also against adherent cells of pathogenic microorganisms forming biofilms. In this context, metal-based coatings with antibacterial activities have been widely investigated and used in the clinical practice. However, traditional coatings exhibit some drawbacks related to the insufficient adhesion to the substrate, scarce uniformity and scarce control over the toxic metal release reducing the biofilm formation prevention efficacy. Additionally, standardized and systematic approaches to test antibacterial activity of newly developed coatings are still missing, while standard microbiological tests (e.g. soft-agar assays) are typically used that are limited in terms of simultaneous conditions that can be tested, potentially leading to scarce reproducibility and reliability of the results. In this work, we combined the Calgary Biofilm Device (CBD) as a device for high-throughput screening, together with a novel plasma-assisted technique named Ionized Jet Deposition (IJD), to generate and test new generation of nanostructured silver- and zinc-based films as coatings for biomedical devices with antibacterial and antibiofilm properties. During the experiments we tested both planktonic and biofilm growth of four bacterial strains, two gram-positive and two gram-negative bacterial strains, i.e. Staphylococcus aureus ATCC 6538P, Enterococcus faecalis DP1122 and Escherichia coli ATCC 8739 and Pseudomonas aeruginosa PAO1, respectively. The use of CBD that had the only wells covered with the metal coatings while the biofilm supports (pegs) were not sheltered allowed to selectively define the toxic effect of the metal release (from the coating) against biofilm development in addition to the toxic activity exerted by contact killing mechanism (on biofilms formed on the coating). The results indicated that the antibacterial and antibiofilm effects of the metal coatings was at least partly gram staining dependent. Indeed, Gram negative bacterial strains showed high sensitivity toward silver in both planktonic growth and biofilm formation, whereas zinc coatings provided a significant inhibitory activity against Gram positive bacterial strains. Furthermore, the coatings showed the maximal activity against biofilms directly forming on them, although, Zn coating showed a strong effect against biofilms of gram-positive bacteria also formed on uncoated pegs. We conclude that the metal-based coatings newly developed and screened in this work are efficient against bacterial growth and adherence opening possible future applications for orthopedic protheses manufacturing

Pre-operative anaemia can present in up to 30% of elective arthroplasty patients. The presence of anaemia increases the risk of requiring blood transfusion post-operatively as well as acts as an independent risk factor for poor outcome such as prosthetic joint infection. Recent international consensus on this topic has recommended a specific care pathway for screening patients with pre-operative anaemia using a simple bedside Heaemacue finger-prick test to detect in a simple and cost-effective manner, and then allow treatment of preoperative anaemia. This pathway was therefore incorporated in our trust. This was a retrospective study done at a single tertiary-referral arthroplasty centre. Our data collection included the Heamacue test results and formal haemoglobin levels if they were performed as well as compliance and costs of each of the tests for patients listed for an elective shoulder, hip and knee arthroplasty between September and December 2018. Medical records and demographics were also collected for these patients for subgroup analysis. Our exclusion criteria comprised patients listed for revision arthroplasty surgery. 87 patients were included in this study. Our compliance rate was 15%. The mean difference between a Haemacue test and a formal FBC result was only 17.6g/L suggesting that it has a reasonably high accuracy. With regards to costs, we found that a Haemacue test costs £2, compared to £7.50 for a full blood count and Haematinics combined. This gave an overall cost saving of £5.50 per patient. Extrapolation of this date locally for 2017 at our hospital, where 1575 primary joint arthroplasties were done, a cost saving of £8,662.5 could have been achieved. Within the UK using data extrapolated from the National Joint Registry a total of £1,102,205.5 (1,221,894 Euros) could have been saved. The use of a single, Haemacue test to screen for pre-operative anaemia in elective arthroplasty patients is more cost effective compared to a formal full count and haematinics tests. However, we found that compliance with the care pathway is variable due to system limitations. This may be addressed through implementing changes to our electronic system in which patients are booked for surgery. We also noted a significant cost reduction if this pathway were to be used Nation-wide. Thus, we encourage other centres to consider the use of the Haemacue test pre-operatively in elective arthroplasty instead of formal full blood counts at the time of decision to treat with arthroplasty; this allows sufficient time for correction of pre-operative anaemia thus improving patient outcomes from arthroplasty

Prosthetic joint infection (PJI) is an uncommon but serious complication of hip replacement. Over 1,000 operations are performed annually in the United Kingdom for PJI following hip replacement, using either one- or two-stage revision arthroplasty. It is unclear which is preferred by patients and which has the best long-term outcome. This qualitative study aims to describe patient experiences of treatment and recovery following one- and two-stage revision arthroplasty for PJI within the context of a pragmatic randomised controlled trial comparing these two approaches. Semi-structured interviews were conducted with 32 patients undergoing one- or two-stage revision treatment for PJI as part of a UK multi-centre randomised controlled trial. Patients were recruited from 12 participating National Health Service (NHS) Orthopaedic Departments and were interviewed 2–4 months after their first revision surgery and again approximately 18 months later. Final sample size was justified on the basis of thematic saturation. All patients consented to the interview being audio-recorded, transcribed, anonymised and analysed using an inductive thematic approach. Ethical approval was provided by NRES Committee South-West Frenchay, 14/SW/116. Patients in both the one- and two-stage treatment groups described prolonged hospital stays, with burdensome antibiotics and brief physiotherapy treatment. However, following discharge home and during recovery, participants undergoing two-stage revision with an ‘empty hip' or with a spacer reported being physically restricted in almost every aspect of their daily life, resulting in inactivity and confinement to home. Mobility aids were not sufficiently available through the health service for these patients. A key difference is that those with a spacer reported more pain than those without. Approximately one year following their second-stage revision, participants described being more independent and active, but two directly attributed muscle weakness to the lengthy period without a hip and described resulting falls or dislocations that had complicated their recovery. In contrast, those undergoing one-stage revision and CUMARS appeared to be more alike, reporting better mobility, functionality and independence, although still limited. Participants in these groups also reported minimal or no pain following their revision. A key difference between CUMARS and one-stage revision was the uncertainty of whether a second operation was necessary, which participants described as “hanging over them”, while those in the two-stage empty hip or spacer group described a more positive anticipation of a second definitive operation as it marked an end to what was described as a detachment from life. Our findings highlight the differences between patient experiences of recovery following revision arthroplasty, and how this is influenced by the surgical approach and presence or lack of spacers. An understanding of lived experiences following one- and two-stage surgical interventions will complement knowledge about the clinical effectiveness of these different types of revision surgery

Prosthetic joint infection (PJI) is an uncommon but serious complication of hip and knee replacement. We investigated the rates of revision surgery for the treatment of PJI following primary and revision hip and knee replacement, explored time trends, and estimated the overall surgical burden created by PJI. We analysed the National Joint Registry for England and Wales for revision hip and knee replacements performed for a diagnosis of PJI and their index procedures from 2003–2014. The index hip replacements consisted of 623,253 primary and 63,222 aseptic revision hip replacements with 7,642 revisions subsequently performed for PJI; for knee replacements the figures were 679,010 primary and 33,920 aseptic revision knee replacements with 8,031 revisions subsequently performed for PJI. Cumulative incidence functions, prevalence rates and the burden of PJI in terms of total procedures performed as a result of PJI were calculated. Revision rates for PJI equated to 43 out of every 10,000 primary hip replacements (2,705/623,253), i.e. 0.43%(95%CI 0.42–0.45), subsequently being revised due to PJI. Around 158 out of every 10,000 aseptic revision hip replacements performed were subsequently revised for PJI (997/63,222), i.e. 1.58%(1.48–1.67). For knees, the respective rates were 0.54%(0.52–0.56) for primary replacements, i.e. 54 out of every 10,000 primary replacements performed (3,659/679,010) and 2.11%(1.96–2.23) for aseptic revision replacements, i.e. 211 out of every 10,000 aseptic revision replacements performed (717/33,920). Between 2005 and 2013, the risk of revision for PJI in the 3 months following primary hip replacement rose by 2.29 fold (1.28–4.08) and after aseptic revision by 3.00 fold (1.06–8.51); for knees, it rose by 2.46 fold (1.15–5.25) after primary replacement and 7.47 fold (1.00–56.12) after aseptic revision. The rates of revision for PJI performed at any time beyond 3 months from the index surgery remained stable or decreased over time. From a patient perspective, after accounting for the competing risk of revision for an aseptic indication and death, the 10-year cumulative incidence of revision hip replacement for PJI was 0.62%(95%CI 0.59–0.65) following primary and 2.25%(2.08–2.43) following aseptic revision; for knees, the figures were 0.75%(0.72–0.78) following primary replacement and 3.13%(2.81–3.49) following aseptic revision. At a health service level, the absolute number of procedures performed as a consequence of hip PJI increased from 387 in 2005 to 1,013 in 2014, i.e. a relative increase of 2.6 fold. While 70% of those revisions were two-stage, the use of single stage revision increased from 17.6% in 2005 to 38.5% in 2014. For knees, the burden of PJI increased by 2.8 fold between 2005 and 2014. Overall, 74% of revisions were two-stage with an increase in use of single stage from 10.0% in 2005 to 29.0% in 2014. Although the risk of revision due to PJI following hip or knee replacement is low, it is rising. Given the burden and costs associated with performing revision joint replacement for prosthetic joint infection and the predicted increased incidence of both primary and revision hip replacement, this has substantial implications for service delivery

Orthopedic metallic medical devices are essential in the treatment of a wide range of skeletal diseases and disabilities. However, they are often related with surgery complications due to acute prosthetic joint infections (PJI) causing devastating complications. Gallium (Ga) antibacterial activity has been recently demonstrated: in aqueous solutions, Ga ionize in a trivalent form Ga. 3+. that can replace Fe. 3+. in bacterial metabolism thus leading to bacteria death. However, it is not yet clear whether such effect is typical to Ga. 3+. release, and how this would affect longer term performance. Here we investigated Ga addition into titanium alloys using metallurgical methods. The study has confirmed that metallurgical addition of gallium even in small amounts (1–2% wt.) to titanium alloys have highly efficient antibacterial function without any visible cytostatic or cytotoxic effects. The presence of gallium within the metal matrix might ensure that antibacterial effect will persist for a long time towards multi-drug resistant S. aureus, which might not be possible if gallium or other metal are only in thin degradable coatings or similar formulations. A 5-logs decrease in CFU number was detected for alloys with 2% Ga and more after 72 h (alamar blue and CFU count assays). The alloys also show to be in vitro cytocompatible with both mature U2OS osteoblasts and progenitor pre-osteoblasts hFOB. Since gallium is metallurgically analogous to aluminium in titanium alloys, it might be used without affecting other alloy 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