Aims. Orthopaedic infection is a potentially serious complication of elective and emergency trauma and orthopaedic procedures, with a high associated burden of morbidity and cost. Optimization of vitamin D levels has been postulated to be beneficial in the prevention of orthopaedic infection. This study explores the role of vitamin D in orthopaedic infection through a systematic review of available evidence. Methods. A comprehensive search was conducted on databases including Medline and Embase, as well as grey literature such as Google Scholar and The World Health Organization Database. Pooled analysis with weighted means was undertaken. Results. Pooled analysis of four studies including 651 patients found the mean 25(OH)D level to be 50.7 nmol/l with a mean incidence of infection of 70%. There was a paucity of literature exploring prophylactic 25(OH)D supplementation on reducing orthopaedic infection, however, there was evidence of association between low 25(OH)D levels and increased incidence of orthopaedic infection. Conclusion. The results indicate a significant proportion of orthopaedic patients have low 25(OH]D levels, as well as an association between low 25(OH)D levels and orthopaedic infection, but more randomized controlled trials need to be conducted to establish the benefit of prophylactic supplementation and the optimum regimen by dose and time. Cite this article: Bone Jt Open 2021;2(9):721–727

Aim. This study aimed to evaluate the impact on length of hospital stay from dedicated infectious diseases input for orthopaedic infection patients compared to sporadic infection specialist input. Method. We conducted an observational cohort study of 157 adults with orthopaedic infections at a teaching hospital in the UK. The orthopaedic infections included were: osteomyelitis, septic arthritis, infected metalwork and prosthetic joint infections, and adults were aged 18 years or more. Prior to August 2016, advice on orthopaedic infection patients was adhoc with input principally from the on-call infectious diseases registrar and phone calls to microbiology whereas after August 2016 these patients received regular input from dedicated infectious diseases doctor(s). The dedicated input involved bedside reviews, medical management, correct antimicrobial prescribing, managing adverse drug reactions, increased use of outpatient parenteral antimicrobial therapy (OPAT) services especially self-administration of intravenous antibiotics and shared decision-making for treatment failure, whilst remaining under orthopaedic team care. Orthopaedic patients operated on for management of their infection between 29/8/16 and 15/3/17 were prospectively identified and orthopaedic operation records were used to retrospectively identified patients between 29/8/15 and 15/3/16. The length of stay was compared between the 2 groups. Results. There were 83 patients in the dedicated infectious diseases input group (dedicated group) and 74 patients in the sporadic infection specialist input group (sporadic group). The dedicated group were significantly younger: median 58 years versus 69years (p<0.001), and there was a trend to significant differences in the breakdown of diagnosis (p=0.06), but no significant sex difference. The median length of stay for the sporadic group was 20 days (interquartile range (IQR) 13–29 days) compared to 14 days (IQR 9–27 days) for the dedicated group, with a trend to significance (p=0.06) but no effect from age or diagnosis. Our hospital values one day in hospital at £864, therefore over the 6.5 months trial period of the dedicated infectious diseases input there was a cost saving of £430,272 (£864 × 6 days × 83 patients). Conclusions. Dedicated infectious diseases input would be expected to improve patient care but by additionally reducing median length of stay for orthopaedic infection patients, this encourages investment to achieve both. In this era of increased scrutiny of health budgets demonstrating value for money, not just improved quality of patient care, is essential

Aim. Diagnosing Orthopaedic infection is limited by the sensitivity of culture methods. Next generation sequencing (NGS) offers an alternative approach for detection of microorganisms from clinical specimens. However, the low ratio of pathogen DNA to human DNA often inhibits detection of microorganisms from specimens. Depletion of human DNA may enhance the detection of microbial DNA. 1. Our aim was to compare four DNA extraction methods for the recovery of microbial DNA from orthopaedic samples for NGS. Method. Simulated samples; pooled culture negative sample matrix was spiked with known concentrations of microorganisms, each panel consisting of 7 samples. Broth culture was performed on simulated samples for comparison with NGS. *. . DNA Extraction; total nucleic acid extraction was performed on an automated extraction platform. **. using the viral NA assay. Modifications included: (1) mechanical lysis (glass beads), (2) lysis of human cells (saponin 0.025%), turbo DNase treatment and (3) mechanical lysis and addition of MspJI enzyme post-extraction for methylated DNA digestion. Detection of human and microbial DNA; human endogenous (HE) gene rtPCR. ***. was utilised following manufacturer's recommendations. Microbial DNA was detected using SYBR green 16s ribosomal RNA rtPCR with high resolution melt-curve analysis. ****. . Results. Broth culture recovered 64% (9/14) of the microorganisms from simulated samples. A significant increase (p<0.01) in the cycle threshold (C. T. ) (median C. T. 25.9 IQR 25.5, 26.1) of the HE gene rtPCR was observed using extraction method b, indicating a significant reduction in human DNA. No significant change (p=0.38) in the C. T. of the HE gene rtPCR was observed between the baseline method (median C. T. 19.2 IQR 18.5, 19.7) and modifications a (median C. T. 18.4 IQR 18.2, 19.4) and c (median C. T. 19.3 IQR 18.6, 19.4). Detection of microbial DNA was successful using the base line extraction method and modification a. Microbial DNA was not detected using the 16s ribosomal RNA rtPCR for modifications b and c. Conclusions. This study has demonstrated that modification of DNA extraction methods using selective enzymatic digestion of human DNA negatively impacts on the recovery of microbial DNA from simulated specimens. Total DNA extraction allows the successful recovery of microbial DNA alongside a significant amount of human DNA. The effect of the presence of human DNA will be subsequently assessed through NGS CosmosID analysis to establish if NGS is more sensitive than broth based culture

Local antimicrobial therapy is an integral aspect of treating orthopaedic device related infection (ODRI), which is conventionally administered via polymethylmethacrylate (PMMA) bone cement. PMMA, however, is limited by a suboptimal antibiotic release profile and a lack of biodegradability.

In this study, we compare the efficacy of PMMA versus an antibioticloaded hydrogel in a single- stage revision for chronic methicillin-resistant Staphylococcus aureus (MRSA) ODRI in

sheep. Antibiofilm activity of the antibiotic combination (gentamicin and vancomycin) was determined in vitro. Swiss alpine sheep underwent a single-stage revision of a tibial intramedullary nail with MRSA infection. Local gentamicin and vancomycin therapy was delivered via hydrogel or PMMA (n = 5 per group), in conjunction with systemic antibiotic therapy. In vivo observations included: local antibiotic tissue concentration, renal and liver function tests, and quantitative microbiology on tissues and hardware post-mortem.

There was a nonsignificant reduction in biofilm with an increasing antibiotic concentration in vitro (p = 0.12), confirming the antibiotic tolerance of the MRSA biofilm. In the in vivo study, four out of five sheep from each treatment group were culture negative. Antibiotic delivery via hydrogel resulted in 10–100 times greater local concentrations for the first 2–3 days compared with PMMA and were comparable thereafter. Systemic concentrations of gentamicin were minimal or undetectable in both groups, while renal and liver function tests were within normal limits.

This study shows that a single-stage revision with hydrogel or PMMA is equally effective, although the hydrogel offers certain practical benefits over PMMA, which make it an attractive proposition for clinical use.

Background

Staphylococcus epidermidis is one of the main organisms associated with prosthetic joint infections. One of the major pathogenic attributes of this organism is the ability to form biofilms, making it extremely resistant to currently available antimicrobial therapies. There is, therefore, an urgent requirement for novel agents that are effective against this organism. Antimicrobial peptides represent a novel group of agents that show good activity towards biofilm-forming S. epidermidis. Antimicrobial peptides are particularly interesting due to their multiple modes of action which are thought to reduce the rate of resistance development to the agents.

Aim. In this study we investigated the effects of non-steroidal anti-inflammatory drugs (NSAIDs) with different cyclooxygenase (COX) selectivity on orthopaedic device-related infections (ODRIs) in a rat model. Specifically, we aimed to measure the impact of NSAID therapy on bone changes, bacterial load, and cytokine levels after treatment with antibiotics. In addition, we compared the effects of long vs short-term celecoxib (a COX-2 inhibitor) treatment on the same outcomes. Method. Skeletally mature female Wistar rats were implanted with Staphylococcus epidermidis-contaminated polyetheretherketone (PEEK) screws (1.5 × 10. 6. CFU per screw) in the proximal right tibia and monitored for 7 days. All animals received subcutaneous antibiotics (rifampicin plus cefazolin) for two weeks from day 7 to 21. In phase I of the study, rats were randomly assigned to receive 28 days of oral treatment with acetylsalicylic acid, ibuprofen, celecoxib, or vehicle control. In phase II, an additional group received seven days of celecoxib treatment from day 0 to 7. After implantation, bone changes were monitored using in vivo micro-CT and histology. Quantitative bacteriology was performed at euthanasia. Plasma samples were collected to measure cytokine levels at four time points (day 0, 6, 20, and 28). Results. The combination of antibiotic therapy resulted in treatment success in 85.71% of cases, while the addition of long-term celecoxib treatment reduced it to 45.45%. Long-term celecoxib treatment significantly reduced bone loss (33.85% mean difference [95% CI 14.12–53.58], p=0.0004 on day 6 bone fraction) and periosteal reaction (0.2760 μm mean difference [95% CI 0.2073–0.3448], p<0.0001 on day 14 periosteal thickness) during the early post-infection period compared to the control group. Short-term celecoxib treatment showed similar radiological results, however, there was no significant reduction in treatment success in the celecoxib group (88.9%). No differences in the selected inflammatory markers were observed. Conclusion. Our findings highlight the potential benefits of short-term use of celecoxib in improving bone fraction during the early post-infection period without impairing the efficacy of antibiotic therapy. This study suggests that celecoxib may be a useful addition to the multimodal approach to pain management in orthopaedic device-related infections

Aim. Culture of multiple periprosthetic tissue samples is the current gold-standard for microbiological diagnosis of prosthetic joint infections (PJI). Additional diagnostic information may be obtained through sonication fluid culture of explants. These current techniques can have relatively low sensitivity, with prior antimicrobial therapy or infection by fastidious organisms particularly influencing culture results. Metagenomic sequencing has demonstrated potential as a tool for diagnosis of bacterial, viral and parasitic infections directly from clinical samples, without the need for an initial culture step. We assessed whether metagenomic sequencing of DNA extracts from sonication fluid can provide a sensitive tool for diagnosis of PJI compared to sonication fluid culture. Method. We compared metagenomic sequencing with standard aerobic and anaerobic culture in 97 sonication fluid samples from prosthetic joint and other orthopaedic device-related infections. Sonication fluids were filtered to remove whole human cells and tissue debris, then bacterial cells were mechanically lysed before DNA extraction. DNA was sequenced and sequencing reads were taxonomically classified using Kraken. Using 50 derivation samples, we determined optimal thresholds for the number and proportion of bacterial reads required to identify an infection and confirmed our findings in 47 independent validation samples. Results. A total of 131 sonication fluids were aerobically and anaerobically cultured and underwent metagenomic sequencing. From the first 72 sonication fluid samples sequenced 22 samples from six batches were excluded, as these samples and negative controls from the same batches showed similar contamination. The remaining 50 samples, the derivation set, were used to determine optimal sequence thresholds for identifying true infection. Of 59 subsequently sequenced validation samples, 12 from a single batch were excluded as the negative control was contaminated with Propionibacterium acnes, leaving 47 validation samples. Compared to sonication fluid culture, the species-level sensitivity of metagenomic sequencing was 61/69(88%,95%CI 77–94%)(derivation samples 35/38[92%,79–98%]; validation samples 26/31[84%,66–95%]), and genus-level sensitivity was 64/69(93%,84–98%). Species-level specificity, adjusting for plausible fastidious causes of infection, species found in concurrently obtained tissue samples, and prior antibiotics, was 85/97(88%,79–93%)(derivation 43/50[86%,73–94%], validation 42/47[89%,77–96%]). High levels of human DNA contamination were seen despite use of laboratory methods to remove it. Conclusions. We demonstrate as a proof of principle that metagenomic sequencing can provide accurate diagnostic information in PJI. Further depletion of human DNA will lead to improved genomic information on the cause of infection, strengthening the case for metagenomic sequencing as a diagnostic tool in PJI

Aim. Diagnostics of orthopedic implant infection remains challenging and often shows false negative or inadequate results. Several methods have been described to improve diagnostic methods but most of them are expensive (PCR) or not accessible for all hospitals (sonication). Aim of this study was to evaluate the results of incubation of orthopedic explants compared to biopsies and punction fluid using conventional microbiological methods. Method. In this prospective study, we included patients who received septic or aseptic orthopedic implant removal in a single University hospital between July and December 2018. A part of the explant as well as minimum 2 tissue biopsies or additional punction fluid were put in a bouillon and incubated for 11 days. Patient´s records with co-morbidities, use of antibiotics and demographic data were evaluated. The results were analyzed. The study was approved by the ethical committee. Results. 94 patients were included in this study (43 females, 51 males, mean age 54 years). We detected statistically significant more pathogens in the bouillon with explants compared to biopsies (p=0,0059). We found the same results with pedicle screws (n=11, p=0,039) and endoprosthesis (n=56, p=0,019). Patients after osteosynthesis (p=27) showed same results but statistically not significant (p=0,050). Use of antibiotics did not have influence on the diagnostic result as well as co-morbidities. In 38 patients (40,4%), additional bacteria could be detected in explant´s bouillon. Most common pathogens were Staph. aureus, E. faecalis, Staph. epidermidis and Micrococcus luteus, mixed infections could be found in 9%. Conclusions. In this study we could show that incubation of orthopedic implants has advantages in diagnostics of pathogens in infected endoprosthesis, osteosynthesis and spondylodesis. This method is simple compared to PCR or sonication and as cheap as incubation of tissue samples but in 40% of the cases, additional pathogens can be detected. We recommend to incubate removed screws, hip endoprosthetic heads or inlays in bouillon to optimize diagnostics and to detect all pathogens

Aim. Orthopedic implant related surgical site infection (SSI) is a severe complication which represents an important challenge concerning to its treatment. Therefore, gram-negative orthopedic infections have recently become a global concern. Method. Retrospective study through searching of the SCIH (infection control service) database, concerning to the year 2016 and 2017. Cases selected were those of implant placement clean surgeries (osteosynthesis or prosthetic placement) which evolved with SSI and Gram-negative bacterial growth in bone tissue or periprosthetic cultures. Results. During 2016 and 2017, 6150 clean surgeries with orthopedic implant placement were performed; 140 fulfilled SSI criteria (83 cases of open fracture reduction, 44 of hip arthroplasty, 13 of knee arthroplasty). Main agent of infections was Staphylococcus aureus (32,47%) mostly of them methicillin-sensitive (69,20%). However, Gram-negative bacteria were responsible for 64,95% of infections. (Klebsiella pneumoniae 12.8%; Acinetobacter baumannii and Enterobacter ssp 11.96%; Pseudomonas aeruginosa 9.40%) Among them, 100% Enterobacter ssp. were sensitive to carbapenems and 75% to ciprofloxacin. Klebsiella pneumoniae showed sensitivity to carbapenems in 85.7%, Pseudomonas aeruginosa showed sensitivity in 85.7% to carbapenems and 100% to ciprofloxacin. Acinetobacter baumannii showed the least favorable profile amongst Gram-negatives since only 12.5% of strains were sensitive to carbapenems, 28.6% to Ampicilin-sulbactam, 22.2% to ciprofloxacin, while showing 100% sensitivity to polymyxins. 14 patients in whom Acinetobacter baumannii was isolated were predominantly elderly (median 70 years), most of them have underlying/chronic diseases (71.42%) such as diabetes, arterial hypertension, alcoholism, smoking and heart failure. None presented sepsis related to this infection, but four of them died as result of hospitalization related complications (28,60% mortality rate). Among these deaths, 3 were related to total hip arthroplasty, and one to knee arthroplasty. One patient died as result of external causes. Among the survivors, five showed remission/cure. The follow up was lost in 4 patients. Conclusions. SSI caused by carbepenem-resistant Acinetobacter baumannii represents considerable impact on morbi-mortality in patients who undergo surgery with placement of orthopedic implants

We investigated the effects of non-steroidal anti-inflammatory drugs (NSAIDs) with different cyclooxygenase (COX) selectivity on orthopaedic device-related infections (ODRIs) in a rat model. We aimed to measure the impact of NSAID therapy on bone changes, bacterial load, and cytokine levels after treatment with antibiotics. We also compared the effects of long vs short-term celecoxib (a COX-2 inhibitor) treatment on the same outcomes. Skeletally mature female Wistar rats were implanted with Staphylococcus epidermidis- contaminated polyetheretherketone (PEEK) screws in the proximal right tibia and monitored for 7 days. All animals received subcutaneous antibiotics (rifampicin plus cefazolin) for two weeks from day 7 to 21. In phase I of the study, rats were randomly assigned to receive 28 days of oral treatment with acetylsalicylic acid, ibuprofen, celecoxib, or vehicle control. In phase II, an additional group received seven days of celecoxib treatment from day 0 to 7. Bone changes were monitored using in vivo micro-CT and histology. Quantitative bacteriology was performed at euthanasia. Plasma samples were collected to measure cytokine levels on days 0, 6, 20, and 28. Combination antibiotic therapy resulted in treatment success in 85.71% of cases, while the addition of long-term celecoxib treatment reduced it to 45.45%. Long-term celecoxib treatment significantly reduced bone loss (33.85% mean difference [95% CI 14.12–53.58], p=0.0004 on day 6 bone fraction) and periosteal reaction (0.2760 μm mean difference [95% CI 0.2073–0.3448], p<0.0001 on day 14 periosteal thickness) during early infection compared to the control group. Short- term celecoxib treatment showed similar radiological results without a reduction in treatment success (88.9%). No differences in the inflammatory markers were observed. Our findings highlight the potential benefits of short-term use of celecoxib in improving bone fraction during the early post-infection period without impairing the efficacy of antibiotic therapy

Aim. Non-steroidal anti-inflammatory drugs (NSAIDs) are a cornerstone of perioperative pain management in orthopedic trauma surgery, although concerns persist regarding the potential impact of these drugs on fracture healing. Furthermore, NSAIDs may also exert an influence on host immune defenses, which may also be important in the context of infection treatment. However, this has been very much under-investigated in the clinical and scientific literature. The aim of this study was to determine the impact of NSAIDs on the course of an orthopedic device-related infection (ODRI) and its response to antibiotic therapy in a rat model. Method. A polyetheretherketone (PEEK) screw was inserted in the proximal tibia of 48 skeletally mature female Wistar rats: 12 control animals received a sterile screw, of which 6 also received NSAID therapy (carprofen, 5 mg/kg s.c. once daily); 36 rats received a Staphylococcus epidermidis-inoculated screw, of which 18 received NSAID therapy. Antibiotic therapy was administered from day 7–21 in 9 animals from all groups receiving S. epidermidis-inoculated screws (cefazolin: 30 mg/kg; s.c., b.i.d. plus rifampin: 25 mg/kg; s.c., b.i.d.). Bone histomorphometric changes were monitored using longitudinal microCT scanning, performed postoperatively, and at 3, 6, 9, 14, 20 and 28 days (euthanasia). Quantitative bacteriology of the implant, bone and overlying soft tissue was performed to assess infection status of individual animals. Results. All animals receiving S. epidermidis-inoculated screws in the absence of antibiotic therapy were confirmed as infected at euthanasia. Quantitative microbiology showed no significant change in bacterial load in NSAID-treated animals versus control. However, NSAID administration dramatically impaired antibiotic efficacy, with 7/8 animals remaining infected when NSAIDs were co-administered, whilst only 2/9 of control animals were infected when NSAIDs were withheld. Pronounced osteolysis was observed by day 6–9 in control animals, with reparative processes (periosteal proliferation and mineralization) observed at day 14. NSAID treatment markedly prevented S. epidermidis-induced osteolysis, but also reparative processes. Antibiotic treatment did not affect the bone changes. Conclusions. NSAID administration dramatically affected the response of bone tissue to infection, reducing osteolysis but also impairing reparative processes. Crucially, NSAIDs dramatically reduced antibiotic efficacy. Given these pronounced negative effects, further investigations should be conducted to determine the underlying pathophysiological mechanism and better understand the consequences of the therapeutic use of NSAIDs in human patients with ODRI

Collection of 4–5 independent peri-prosthetic tissue samples is recommended for microbiological diagnosis of prosthetic joint infections. Sonication of explanted prostheses has also been shown to increase microbiological yield in some centres. We compared sonication with standard tissue sampling for diagnosis of prosthetic joint and other orthopaedic device related infections. We used standard protocols for sample collection, tissue culture and sonication. Positive tissue culture was defined as isolation of a phenotypically indistinguishable organism from ≥2 samples; and positive sonication culture as isolation of an organism at ≥50 cfu/ml. We compared the diagnostic performance of each method against an established clinical definition of infection (Trampuz 2011), and against a composite clinical and microbiological definition of infection based on international consensus (Gehrke & Parvizi 2013). 350 specimens were received for sonication, including joint prostheses (160), exchangeable components (76), other orthopaedic hardware and cement (104), and bone (10). A median of 5 peri-prosthetic tissue samples were received from each procedure (IQR 4–5). Tissue culture was more sensitive than sonication for diagnosis of prosthetic joint and orthopaedic device related infection using both the clinical definition (66% versus 57%, McNemar's Χ2 test p=0.016) and the composite definition of infection (87% vs 66%, p<0.001). The combination of tissue culture and sonication provided optimum sensitivity: 73% (95% confidence interval 65–79%) against the clinical definition and 92% (86–96%) against the composite definition. Results were similar when analysis was confined to joint prostheses and exchangeable components; other orthopaedic hardware; and patients who had received antibiotics within 14 days prior to surgery. Tissue sampling appears to have higher sensitivity than sonication for diagnosis of prosthetic joint and orthopaedic device infection at our centre. This may reflect rigorous collection of multiple peri-prosthetic tissue samples. A combination of methods may offer optimal sensitivity, reflecting the anatomical and biological spectrum of prosthetic joint and other device related infections

Aim. Smoking is known to impair wound healing and to increase the risk of peri-operative adverse events and is associated with orthopaedic infection and fracture non-union. Understanding the magnitude of the causal effect on orthopaedic infection recurrence may improve pre-operative patient counselling. Methods. Four prospectively-collected datasets including 1173 participants treated in European centres between 2003 and 2021, followed up to 12 months after surgery for clinically diagnosed orthopaedic infections, were included in logistic regression modelling with Inverse Probability of Treatment Weighting for current smoking status [1–3]. Host factors including age, gender and ASA score were included as potential confounding variables, interacting through surgical treatment as a collider variable in a pre-specified structural causal model informed by clinical experience. The definition of infection recurrence was identical and ascertained separately from baseline factors in three contributing cohorts. A subset of 669 participants with positive histology, microbiology or a sinus at the time of surgery, were analysed separately. Results. Participants were 64% male, with a median age of 60 years (range 18–95); 16% of participants experienced treatment failure by 12 months. 1171 of 1173 participants had current smoking status recorded. As expected for the European population, current smoking was less frequent in older participants (Table 1). There was no baseline association between Charlson score or ASA score and smoking status (p=0.9, p=1, Chi squared test). The estimated adjusted odds ratio for treatment failure at 12 months, resulting from current smoking at the time of surgery, was 1.37 for all participants (95% CI 0.75 to 2.50) and 1.53 for participants with recorded confirmatory criteria (95% CI 1.14 to 6.37). Conclusions. Smoking contributes to infection recurrence, particularly in people with unequivocal evidence of osteomyelitis or PJI. People awaiting surgery for orthopaedic infection should be supported to cease smoking, not only to reduce anaesthetic risk, but to improve treatment outcomes. Limitations of this study include unmeasured socioeconomic confounding and social desirability bias resulting in uncertainty in true smoking status, resulting in underestimated effect size

Aim. Recurrence of bone and joint infection, despite appropriate therapy, is well recognised and stimulates ongoing interest in identifying host factors that predict infection recurrence. Clinical prediction models exist for those treated with DAIR, but to date no models with a low risk of bias predict orthopaedic infection recurrence for people with surgically excised infection and removed metalwork. The aims of this study were to construct and internally validate a risk prediction model for infection recurrence at 12 months, and to identify factors that predict recurrence. Predictive factors must be easy to check in pre-operative assessment and relevant across patient groups. Methods. Four prospectively collected datasets including 1173 participants treated in European centres between 2003 and 2021, followed up to 12 months after surgery for orthopaedic infections, were included in logistic regression modelling [1–3]. The definition of infection recurrence was identical and ascertained separately from baseline factors in three contributing cohorts. Eight predictive factors were investigated following a priori sample size calculation: age, gender, BMI, ASA score, the number of prior operations, immunosuppressive medication, glycosylated haemoglobin (HbA1c), and smoking. Missing data, including systematically missing predictors, were imputed using Multiple Imputation by Chained Equations. Weekly alcohol intake was not included in modelling due to low inter-observer reliability (mean reported intake 12 units per week, 95% CI for mean inter-rater error −16.0 to +15.4 units per week). Results. Participants were 64% male, with a median age of 60 years (range 18–95). 86% of participants had lower limb orthopaedic infections. 732 participants were treated for osteomyelitis, including FRI, and 432 for PJI. 16% of participants experienced treatment failure by 12 months. The full prediction model had moderate apparent discrimination: AUROC (C statistic) 0.67, Brier score 0.13, and reasonable apparent calibration. Of the predictors of interest, associations with failure were seen with prior operations at the same anatomical site (odds ratio for failure 1.51 for each additional prior surgery; 95% CI 1.02 to 2.22, p=0.06), and the current use of immunosuppressive medications (odds ratio for failure 2.94; 95% CI 0.89 to 9.77, p=0.08). Conclusions. This association between number of prior surgeries and treatment failure supports the urgent need to streamline referral pathways for people with orthopaedic infection to specialist multidisciplinary units

Revision surgeries for orthopaedic infections are done in two stages – one surgery to implant an antibiotic spacer to clear the infection and another to install a permanent implant. A permanent porous implant, that can be loaded with antibiotics and allow for single-stage revision surgery, will benefit patients and save healthcare resources. Gyroid structures can be constructed with high porosity, without stress concentrations that can develop in other period porous structures [1] [2]. The purpose of this research is to compare the resulting bone and prosthesis stress distributions when porous versus solid stems are implanted into three proximal humeri with varying bone densities, using finite element models (FEM). Porous humeral stems were constructed in a gyroid structure at porosities of 60%, 70%, and 80% using computer-aided design (CAD) software. These CAD models were analyzed using FEM (Abaqus) to look at the stress distributions within the proximal humerus and the stem components with loads and boundary conditions representing the arm actively maintained at 120˚ of flexion. The stem was assumed to be made of titanium (Ti6Al4V). Three different bone densities were investigated, representing a healthy, an osteopenic, and an osteoporotic humerus, with an average bone shape created using a statistical shape and density model (SSDM) based on 75 cadaveric shoulders (57 males and 18 females, 73 12 years) [3]. The Young's moduli (E) of the cortical and trabecular bones were defined on an element-by-element basis, with a minimum allowable E of 15 MPa. The Von Mises stress distributions in the bone and the stems were compared between different stem scenarios for each bone density model. A preliminary analysis shows an increase in stress values at the proximal-lateral region of the humerus when using the porous stems compared to the solid stem, which becomes more prominent as bone density decreases. With the exception of a few mesh dependent singularities, all three porous stems show stress distributions below the fatigue strength of Ti-6Al-4V (410 MPa) for this loading scenario when employed in the osteopenic and osteoporotic humeri [4]. The 80% porosity stem had a single strut exceeding the fatigue strength when employed in the healthy bone. The results of this study indicate that the more compliant nature of the porous stem geometries may allow for better load transmission through the proximal humeral bone, better matching the stress distributions of the intact bone and possibly mitigating stress-shielding effects. Importantly, this study also indicates that these porous stems have adequate strength for long-term use, as none were predicted to have catastrophic failure under the physiologically-relevant loads. Although these results are limited to a single boney geometry, it is based on the average shape of 75 shoulders and different bone densities are considered. Future work could leverage the shape model for probabilistic models that could explore the effect of stem porosity across a broader population. The development of these models are instrumental in determining if these structures are a viable solution to combatting orthopaedic implant infections

Correct diagnosis of infection is crucial for an adequate treatment of orthopedic implant-related infections. In the orthopedic field, infections can be difficult to diagnose(1). As a consequence, patients may suffer from an undiagnosed and untreated implant-related infection. To solve this problem, we are searching for a diagnostic method to detect these so-called low-grade infections. The technique fluorescence in situ hybridization (FISH) can detect slow-growing and even dead bacteria. Further, as FISH results are available within an hour after tissue collection it is an ideal candidate for diagnostic purposes. AIM: to evaluate the FISH technique for its potential to detect and identify orthopedic infections. Sonication fluid (SF) was collected by sonicating retrieved implants(2) from 62 patients. All samples were subjected to bacterial culture for clinical diagnostics. In addition, a commercially available FISH kit (miacom diagnostics, Germany), specifically designed for blood analysis (hemoFISH Masterpanel), was used. The kit contained 16S rRNA probes (positive control), non-sense probes (negative control), probes for Staphylococcus spp., Staphylococcus aureus, Streptococcus spp., Streptococcus pneumoniae, Streptococcus agalactiae, Enterococcus faecium, Enterococcus faecalis, Enterobacteriaceae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Acetinobacter spp., and Stenotrophomonas maltophilia. All FISH analyses were performed according to the protocol provided with the kit. Culture and FISH results were compared, considering culture as the gold standard. Culture resulted in 27 positive and 35 negative samples. Comparing FISH (16S rRNA probe) with culture, 24 samples tested true-positive and 32 samples true-negative. Furthermore, 3 samples tested false-negative and 3 samples false-positive. The species cultured with the highest incidence were Propionibacterium acnes and Staphylococcus epidermidis, both from 8 SF samples. As the kit did not contain a probe for Propionibacterium acnes, these strains were only detected by the 16S rRNA probe. In addition, the latter samples tested positive with the Staphylococcus spp. probe. Interestingly, 3 samples tested positive with FISH that were culture negative. This result could indicate a higher sensitivity for detection of bacteria with FISH than with culture. Before FISH can be used for diagnostic purposes, the technique needs to be optimized to prevent false-negative results, for use on other patient materials and for detection of bacterial strains relevant for the orthopedic field like Propionibacterium acnes. In conclusion, FISH holds promise to be used as a diagnostic tool for identifying orthopedic infections

Aims and Objectives. To assess the efficacy of linezolid in the treatment of orthopaedic related infection and the instance of adverse reactions. Methods. The management of 22 patients treated with oral linezolid for orthopaedic related infections were reviewed. Patients were selected from the hospital database using clinical coding related to orthopaedic infections and all patients were managed within a single tertiary referral centre. These included infected joint arthroplasty (10 patients), infection following fracture fixation (8 patients), septic arthritis and soft tissue infection (non trauma 4 patients). All patients were treated with oral linezolid therapy, and in each case treatment was initiated with the involvement of a microbiologist, as per trust anti-microbial policy. A diagnosis of infection was confirmed on basis of both subjective and objective markers. Results. 77% of patients resolution of infection at follow up (mean length of follow up 28 months) with mean C reactive protein showing a significant (p<0.05) reduction from 123 mg/l to 13.2 mg/l. This included 87.5% resolution in the infection following fracture fixation, 80% in the infected arthroplasty and 75% in the non trauma related infection groups. Adverse reactions were observed in 3 patients. Conclusion. This study demonstrates linezolid offers an excellent alternative treatment option, along with appropriate surgical management, for the management of orthopaedic related infections, with few adverse side effects. Traditionally, this cohort of patients has required lengthy in hospital admission for intra venous antibiotics. Our study demonstrates that use of linezolid may facilitate early hospital discharge in patients with orthopaedic related infections, since it is 100% bioavailable with oral administration, albeit with regular monitoring of blood parameters

The incidence of PJI in knee replacements is 2.8% and slightly lower with hip replacement surgery. PJI make up 15% (or even more) of knee revisions. To combat PJI, antibiotic laden bone cement has been used for many decades, but antibiotic stewardship dictates more prudent management of antimicrobials. Projected increase in infection rate, due to increased surgery and latent infection to be almost 5-fold up to 2035. Biofilm is a complex structure of bacteria and polysaccharide matrix and, is recognised as a major component in PJI and other orthopaedic infections. Biofilm is responsible for high incidence of resistance to antimicrobials and ineffective host immune response. Method. Stabilized hypochlorous acid has been reported to have a rapid kill rate on all pathogens, including MDR pathogens associated with chronic and acute wound infections. It destroys biofilm on contact, is not cytotoxic, reduces inflammation and stimulates wound healing. 0,038% of Hypochlorous acid was used as prophylaxis against infection and to treat PJI. We report on our experience with hypochlorous acid as a wound irrigation as prophylaxis against infection (more than 600 cases) and for PJI. We also report on a University study where a head to head analysis was done on the anti-biofilm efficacy between hypochlorous acid 0,038% (Trifectiv Surgical Wound Irrigation) and Product X (an industry-standard product for the prevention and treatment of biofilm infection. Hypochlorous acid offers a valuable addition to the armamentarium of wound antiseptics, with added anti-inflammatory value. An in vitro study demonstrated superior efficacy against biofilm when compared to Product X

Aim. We reviewed a cohort of individuals with recurrent orthopaedic infection to describe the relative rates of microbial persistence vs re-infection at recurrence surgery. Method. A cohort of 125 individuals with recurrent infection (prosthetic joint infection, fracture-related infection and osteomyelitis) from two centres in the UK between 2007 and 2021. Electronic patient records were reviewed to identify culture results from surgical samples at index surgery and the next operation for recurrent infection. Antibiotic sensitivity results were recorded as sensitive, intermediate or resistant according to contemporary sensitivity testing guidelines. Results. Among patients with recurrent infection, 78/125 (62.4%) were male, with a median age 64 years (IQR 51–73y). 76 had prosthetic joint infection, and 49 had fracture related infection or osteomyelitis. Culture results at index procedure showed the most frequently isolated species were Staphylococci (Table 1). A single species was isolated in 75/125 (60%) and mixed species in 36/125 (28.8%). No organisms were cultured in 14/125 (11.2%). At re-operation 48/125 (38.4%) individuals had an organism from the same species or group as at the index operation. In 49/125 (39.2%), none of the organisms isolated at re-operation were grown at first operation. In 28/125 (22.4%), re-operative cultures yielded no growth. For each species isolated at the index procedure, the proportion with the same, different or no organisms isolated at the next procedure were reviewed (Table 1). Staphylococci (including S. aureus and coagulase-negative staphylococci) and Pseudomonas species showed the highest rate of persistence at the species level. Among coagulase-negative staphylococci, changes in antimicrobial sensitivity that make it unclear if these infections were truly persistent, or represented re-infection. Conclusions. Infection with different organisms was seen at similar rates (39.2% vs 38.4%) to persistent infection with the same species in this cohort. Staphylococcus aureus is the organism most likely to be persistently identified in recurrent infections

Aim. There is a lack of data supporting the use of doxycycline as a single agent after removing infected orthopaedic metalwork. We evaluated the efficacy and safety of doxycycline compared with other single antibiotic regimens used at our specialist orthopaedic hospital. Methods. A retrospective observational study including all adult patients diagnosed with an orthopaedic metalwork infection due to staphylococci. All patients were managed with the removal of metalwork, and multiple intraoperative samples were sent for culture, followed by the administration of at least four weeks of oral antibiotics. Antibiotic selection was on the recommendation of an infection consultant. Infection outcome was assessed as the proportion of patients meeting the OVIVA Trial definition of definite failure at follow-up. The probability of definite failure for doxycycline and the alternatives group was estimated using the Kaplan-Meier survival method. All adverse drug reactions (ADR) during treatment were analysed. Results. Seventy-nine orthopaedic metalwork infections were identified between July 2017 and July 2021. Forty-four were prosthetic joints, and 35 were fracture-related metalwork. In 54 cases, the infecting organism was Staphylococcus aureus, and 25 were due to coagulase-negative staphylococci. Forty-four were treated with doxycycline 100mg 12 hourly, and 35 were treated with alternatives (flucloxacillin 1g 6-hourly n=21 and clindamycin 450mg 6-hourly n=14). Overall, 70 patients (88.6%) were infection-free after a median follow-up of 23 months (IQR, 19 – 44). 38 (82.3%) were infection-free in the doxycycline group compared with 32 (91.4%) patients treated with alternatives. Of the failures in the alternatives group, all 3 received flucloxacillin. Survival analysis showed no significant difference in time to treatment failure between doxycycline and alternative antibiotics. Eighteen patients experienced an ADR: 2 nausea, one rash and one vaginal candidiasis due to doxycycline. Four diarrhoea, one reflux, two rashes and one headache due to clindamycin; 1 nausea and five diarrhoea due to flucloxacillin. Four patients required discontinuation therapy, two due to clindamycin and two due to flucloxacillin. Conclusions. In our cohort of patients, doxycycline monotherapy was an effective and well-tolerated oral option for treating staphylococcal infection following debridement and removal of orthopaedic metalwork