Aims. Highly cross-linked polyethylene (HXLPE) greatly reduces wear in total hip arthroplasty, compared to conventional polyethylene (CPE). Cross-linking is commonly achieved by irradiation. This study aimed to compare the degree of cross-linking and in vitro wear rates across a cohort of retrieved and unused polyethylene cups/liners from various brands. Methods. Polyethylene acetabular cups/liners were collected at one centre from 1 April 2021 to 30 April 2022. The trans-vinylene index (TVI) and oxidation index (OI) were determined by Fourier-transform infrared spectrometry. Wear was measured using a pin-on-disk test. Results. A total of 47 specimens from ten brands were included. The TVI was independent of time in vivo. A linear correlation (R. 2. = 0.995) was observed between the old and current TVI standards, except for vitamin E-containing polyethylene. The absorbed irradiation dose calculated from the TVI corresponded to product specifications for all but two products. For one electron beam-irradiated HXLPE, a mean dose of 241% (SD 18%) of specifications was determined. For another, gamma-irradiated HXLPE, a mean 41% (SD 13%) of specifications was determined. Lower wear was observed for higher TVI. Conclusion. The TVI is a reliable measure of the absorbed irradiation dose and does not alter over time in vivo. The products of various brands differ by manufacturing details and consequently cross-linking characteristics. Absorption and penetration of electron radiation and gamma radiation differ, potentially leading to higher degrees of cross-linking for electron radiation. There is a non-linear, inverse correlation between TVI and in vitro wear. The wear resistance of the HXLPE with low TVI was reduced and more comparable to CPE. Cite this article: Bone Joint Res 2024;13(11):682–693

Aim. Orthopedic implants play a tremendous role in fixing bone damages due to aging as well as fractures. However, these implants tend to get colonized by bacteria on the surface, leading to infections and subsequently prevention of healing and osteointegration. Recently, Roupie et al. showed that a nisin layer-by-layer based coating applied on biomaterials has both osteogenic and antibacterial properties. The Galleria mellonella larva is a well-known insect infection model that has been used to test the virulence of bacterial and fungal strains as well as for the high throughput screening of antimicrobial compounds against infections. Recently, we have developed an insect infection model with G. mellonella larvae to study implant-associated biofilm infections using Kirschner (K)-wires as implant material. Here, we would like to test the antibacterial capacity of nisin layer-by-layer based coatings on K-wires against Staphylococcus aureus in the G. mellonella larva implant infection model. Method. Prior to the implantation procedure, G. mellonella larvae are maintained at room temperature on wheat germ in an incubator. The larvae received bare titanium K-wires (uncoated), or either control-coated or nisin-coated K-wires. After one hour, the larvae were injected with 5×10. 5. S. aureus bacteria per larva (i.e., hematogenous implant infection model). Next, the larvae were incubated at 37. o. C in an incubator and the survival of the larvae was monitored for five days. Moreover, the number of bacteria on the implant surface and in the surrounding tissue was determined after 24h of incubation. Further, scanning electron microscopy (SEM) analyses were performed to study the effect of nisin on biofilm formation. Results. The larvae receiving the nisin-coated K-wires showed significantly higher survival rates compared to uncoated titanium K-wires, although not when compared to control-coated K-wires. A more than 1-log reduction in number of bacteria on the implant surface and in the surrounding tissue was observed in larvae receiving the nisin-coated K-wires, when compared to uncoated titanium K-wires SEM analysis showed reduced colonization of the bacteria nisin-coated K-wires compared to the controls. Conclusions. In conclusion, the antimicrobial nisin layer-by-layer based coating applied on titanium surfaces is able to prevent implant-related S. aureus biofilm infection in G. mellonella and is a promising antimicrobial strategy to prevent implant-related infections

Aim. An instrumented blood culture system automatically flags when growth within the culture medium has been detected (‘work in progress’), and subsequently when the organism has been identified. We explore using this data to switch patients to oral therapy within 72 hours post-surgery, reducing costs and improving antimicrobial stewardship. Method. This retrospective review focused on clinically significant culture-positive bone and joint infections over a 5-month period in 2022. Two cohorts were defined as either having positive intraoperative microbiology at <72 hours or at ≥72 hours. Results. 150 patients were included. 133/150(88%) exhibited microbial growth <72hours. Of these, 98/133(74%) had all organisms identified <72-hours, and 34/133(26%) had additional organisms ≥72 hours. 19/151(12%) patients had their first positive cultures ≥72hrs from sampling. The most common isolates identified within 72 hours were S. aureus(30%), Enterobacteriaceae (26%), and Coagulase-negative Staphylococcus (CoNS)(19%). If no growth was observed by 48 hours, there was a 69.6% probability that subsequent growth wouldn't occur; this probability increases to 81.9% by 72 hours, 88.7% by 96 hours, 91.0% by 120 hours, and 95.0% by 144 hours (see figure 1). The most common isolates identified ≥72 hours were CoNS(28%), Cutibacterium acnes(16%) and S. aureus(12%). Assessing oral antibiotic regimes for isolates identified after 72 hours demonstrated that linezolid would cover isolates from 96% of patients, tetracyclines 92% of patients, clindamycin 85% of patients, and ciprofloxacin and rifampicin would cover 80% of patients. Vancomycin and meropenem, our standard empirical therapy, gave the best cover at 96% of patients. Conclusions. This study suggests there is sufficient microbiological information at 72 hours for most patients to allow transition to a targeted regimen. If there has been no detection of growth when using an instrumented blood culture system by 72 hours, it is likely that there will be no growth. For any tables or figures, please contact the authors directly

Background. Two-stage revision arthroplasty is the standard treatment for chronic hip and knee periprosthetic joint infections (PJI). Accurate diagnosis of persistent infections at 2nd stage using established biomarkers and diagnostic criteria is of paramount importance. This study aimed to evaluate the diagnostic value of synovial calprotectin and alpha-defensin, and compare established diagnostic criteria from the International Consensus Meeting (ICM 2018) and the European Bone and Joint Infection Society (EBJIS 2021) to determine persistent PJI at the 2nd stage of a two-stage revision arthroplasty. Methods. We retrospectively analyzed 97 patients who underwent 100 two-stage revisions (hip: 39, knee: 61). Synovial fluid samples were assessed for calprotectin and alpha-defensin levels. ICM 2018 and EBJIS 2021 were applied to all patients undergoing 2nd stage revision. Receiver operating characteristic (ROC) curves and Youden Index were utilized to determine optimal cut-off values, and correlations between biomarkers were evaluated. The microbiological spectrum was analyzed at 2nd stage and re-revision surgery. Results. Calprotectin levels showed a sensitivity of 66.7%, specificity of 32.9%, and accuracy of 38.0% in predicting septic failure. Alpha-defensin showed sensitivity of 28.6%, specificity of 87.8%, and accuracy of 79.2%. Significant correlations included: calprotectin with PMN% (r = 0.471, p = 0.05) and alpha-defensin with WBC (r = 0.830, p < 0.01) in the successful cohort. For septic re-revisions, calprotectin and alpha-defensin were highly correlated (r = 0.969, p < 0.01). ICM correctly diagnosed persistent PJI in 26.7%, while EBJIS diagnosed 24.2%. The microbial spectrum shifted from gram-positive to gram-negative bacteria between reimplantation and re-revision surgeries. Conclusion. Synovial calprotectin and alpha-defensin demonstrated limited accuracy in ruling out persistent PJI at reimplantation. The low sensitivity of current diagnostic criteria, combined with the observed shift in microbial spectrum, underscores the challenges in diagnosing persistent PJI during 2nd stage of a two-stage revisions arthroplasty

Aim. The SOLARIO trial is a randomised controlled non-inferiority trial of antibiotic strategy for bone and joint infection. SOLARIO compares short or long post-operative systemic antibiotic duration, for patients with confirmed infections, who had local antibiotics implanted and no infected metalwork retained when undergoing surgery. This analysis compared systemic antibiotic use in the short (intervention) and long (standard of care) arms of the trial, in the 12 months after index surgery. Method. Data was collected prospectively from study randomisation, within 7 days of index surgery. All systemic antibiotics prescribed for the index infection were recorded, from health records and patient recall, at randomisation, 6 weeks, 3-6 months and 12 months after study entry. Start and end dates for each antibiotic were recorded. Results. 251 patients were randomised to short systemic antibiotics (up to 7 post-operative days) and 249 patients, to long systemic antibiotics. 5 participants in the short group and 2 participants in the long group withdrew from study follow-up. Complete data for all systemic antibiotics taken in the 12 months following surgery, were available for 237 participants in the short group and 236 participants in the long group. 80 participants across both groups were noted as having deviated from their assigned treatment strategy. Both groups received empiric antibiotics, predominantly vancomycin and meropenem, for up to 7 days after surgery. Considering each prescribed antibiotic as a separate duration (even when administered concurrently), participants assigned to standard care received a mean of 74.9 antibiotic-days. Participants assigned to short systemic antibiotics received a mean of 27.5 antibiotic-days in the 12 months after surgery. The most commonly prescribed antibiotics in both treatment groups were vancomycin and meropenem: these antibiotics accounted for 7.1 days prescribed per participant in the long group, and 6.3 days in the short group (p=0.37). Reasons for post-randomisation antibiotic prescribing in the short treatment group included later planned surgery, identification of bacteria requiring additional systemic antibiotics, and treatment of superficial wound infections. WHO AWaRe classification ‘watch’ and ‘reserve’ group antibiotics, such as ciprofloxacin, rifampicin, vancomycin and meropenem, accounted for 39.4 antibiotic-days per long group participant, and 16.5 antibiotic-days per short group participant. Conclusions. Considering the combined duration of all systemic antibiotics prescribed over 12 months, including those co-administered, participants in the short arm of the SOLARIO trial received considerably fewer days of all antibiotic classes, and particularly those antibiotics restricted in the WHO AWaRe classification (2021)

Abstract. Background. The aim of the present experimental study was to analyse vancomycin elution kinetics of nine bone fillers used in orthopaedic and trauma surgery over 42 consecutive days. Methods. Two allograft bone chips (carriers 1 and 2), a calcium-sulfate matrix (carrier 3), a hydroxyapatite/calcium-sulphate composite (carrier 4), four bone cements (carriers 5-8) and a pure tricalcium phosphate matrix (carrier 9), either already contained vancomycin, or were mixed with it following manufacturer's recommendations. Over 42 days, half of elution medium was substituted by the same amount of PBS at 9 distinct time points. Vancomycin concentration in obtained samples were measured with a kinetic microparticle immunoassay, and masses consecutively calculated. To enhance comparability between carriers analysed, vancomycin mass released related to overall mass within each probe was determined. Notably, elution kinetics of carriers 1 to 4 have been published previously. Results. All carriers initially released high vancomycin masses, followed by constant reduction later into the experiment. Mean initial vancomycin masses released after 4 hours were highest for carriers 1 (337.7 ± 76.2 mg), 9 (68.4 ± 4.9 mg), and 2 (49.0 ± 54.6 mg). From prefinal (35 days) to last measurement (42 days) carriers 2 (8.6 ± 4.8 mg), 1 (2.4 ± 1.0 mg), and 5 (0.1 ± 0.1 mg) had released highest vancomycin masses. Notably, all five bone cements tested only released a small percental amount of their total mass up to the last measurement (42 days; 2.1% – 9.3%), whilst allografts and resorbable synthetic bone fillers discarded high percental values (22.5% – 79.2%). Conclusions. Elution kinetics differ between 9 antibiotic-loaded bone fillers, with high vancomycin masses released by allografts and resorbable bone fillers over time. Transferred to clinical practice, these may be favoured over bone cements in case prolonged and high antibiotic release is warranted rather than mechanical stability

Aims. Pain is the most frequent complaint associated with osteonecrosis of the femoral head (ONFH), but the factors contributing to such pain are poorly understood. This study explored diverse demographic, clinical, radiological, psychological, and neurophysiological factors for their potential contribution to pain in patients with ONFH. Methods. This cross-sectional study was carried out according to the “STrengthening the Reporting of OBservational studies in Epidemiology” statement. Data on 19 variables were collected at a single timepoint from 250 patients with ONFH who were treated at our medical centre between July and December 2023 using validated instruments or, in the case of hip pain, a numerical rating scale. Factors associated with pain severity were identified using hierarchical multifactor linear regression. Results. Regression identified the following characteristics as independently associated with higher pain score, after adjustment for potential confounders: Association Research Circulation Osseous classification stage IIIa or IIIb, bone marrow oedema, grade 3 joint effusion, as well as higher scores on pain catastrophizing, anxiety, and central sensitization. The final model explained 69.7% of observed variance in pain scores, of which clinical and radiological factors explained 37%, while psychological and neurophysiological factors explained 24% and demographic factors explained 8.7%. Conclusion. Multidimensional characteristics jointly contribute to the severity of pain associated with ONFH. These findings highlight the need to comprehensively identify potential contributors to pain, and to personalize management and treatment accordingly. Cite this article: Bone Joint Res 2024;13(11):673–681

Aim. Suppressive antimicrobial therapy (SAT) is used worldwide for patients with a prosthetic joint infection (PJI but clear definitions or guidelines regarding the indications, antimicrobial strategy or treatment duration are currently lacking in the literature. The aim of this study was to identify the global differences in the clinical practice of SAT for PJI. Method. An online survey was designed to investigate the current opinion on indication and treatment goals, preferred antimicrobial drugs, dosing and treatment duration and follow-up of patients with PJI on suppression. The survey was distributed using e-mail lists of several international bone and joint infection societies and study groups. Recipients were asked to share the survey with colleagues who were not a member of one of the societies but who were involved in PJI care. Results. The questionnaire was fully completed by 330 physicians from 43 different countries on six continents (Europe, n=134, 41%; Oceania n=112, 34%; North America, n=51, 16%; other, n=33, 10%; total response rate 14%). Antimicrobial treatment for PJI was discussed in a multidisciplinary team in Europe (90%), Oceania (42%) and North America (12%). In six of eight (75%) different clinical scenarios, respondents from North America would most often place a patient on SAT. In seven of eight (88%) scenarios, SAT was started least often by European respondents. The presence of a fistula was considered a contra-indication for suppression by 74 respondents (22%). First choices of SAT for staphylococcal PJI were: oral cephalosporins (39%) and tetracyclines (31%) in North America; anti-staphylococcal penicillins (55%) and oral cephalosporins (24%) in Oceania; tetracyclines (27%) and anti-staphylococcal penicillins (22%) in Europe. For streptococcal PJI, most clinicians preferred penicillins (91% in Oceania, 67% in Europe, and 53% in North America). Preferred SAT for gram negative PJI was: fluoroquinolones and a penicillin/betalactamase inhibitor in North America (26% and 18%, respectively) and Oceania (23% and 27%, respectively); fluoroquinolones (31%) and Cotrimoxazole (28%) in Europe. The dosage of SAT was never lowered (n=126, 38%), standardly lowered for all antibiotics (n=79, 24%) or only lowered for specific antibiotics (n=125, 38%). SAT was prescribed for an indefinite duration (n=43, 13%), as fixed duration between six months and three years (n=104, 32%) or for an undetermined prespecified duration (n=154, 47%). Conclusions. Substantial variation in the practice of SAT for PJI exists between physicians worldwide and throughout the different continents. This reflects the paucity of data regarding the indication and treatment of PJI with SAT

Aim. Accurate diagnosis is key in correctly managing prosthetic joint infection(PJI). Shoulder PJI definition and diagnosis is challenging. Current PJI definitions, based overwhelmingly in hip/knee research, may not accurately diagnose shoulder PJI. Our aim is to compare the preoperative performance of two PJI definitions comparing it to definitive postoperative classification. Method. This is a retrospective study of patients who have undergone total shoulder revision surgery for infection between 2005 and 2022. Cases were classified using two different PJI definitions: a)the European Bone and Joint Infection Society (EBJIS) and; 2)the 2018 International Consensus Meeting(ICM) PJI specific shoulder definition. Preoperative classification was based on clinical features, inflammatory markers and synovial fluid leukocyte count and definitive classification also considered microbiology and histology results. Results. Preoperative and definitive PJI classification status of the 21 patients included were evaluated and is summarized in table 1. The shoulder specific 2018 ICM definition showed the highest agreement between preoperative and definitive classification (76.2%, k=0.153, p=0.006) compared to EBJIS (52.4%, k=0.205, p=0.006). In all cases, the classification was changed because of positive intraoperative microbiology (at least two identical isolates). Microbiology findings showed coagulase negative staphylococci, Staphyloccocus aureus and Cutibacterium acnes to be the most frequent. Four patients had polymicrobial infections. Conclusions. Both the EBJIS 2021 and 2018 ICM definitions have low accuracy in predicting shoulder PJI preoperatively. Clearly further studies with larger cohorts are in dire need focusing specifically on shoulder revision arthroplasty to improve on existing definitions. Caution is advised while extrapolating of criteria/thresholds recommended for hip/knee joints. For any tables or figures, please contact the authors directly

Aim. The management of PJIs is slowed down by the presence of bacteria forming biofilms where they may withstand antibiotic therapy. The use of adjuvant strategies, such as hydrolytic enzymes cocktail targeting biofilm matrices and facilitating their dispersion, is a promising option to limit impact of biofilms. Our aim was to evaluate the effect of enzymes cocktail combined with antibiotic dual therapy of rifampicin and vancomycin in a relevant in-vitro model. Method. Mature methicillin-resistant Staphylococcus aureus biofilms were grown on Ti-6Al-4V coupons by adding 1mL of a 8Log10 ATCC 33591 suspension in TGN (TSB + 1% glucose + 2% NaCl) to 24-wells plates containing the coupons and incubating the plates for 24h at 37°C with a continuous 50rpm agitation. The samples were rinsed and placed in 6 wells plates containing 1ml of the enzymatic cocktail (C.D.D.) solution (tris-buffered (pH 7.0) solution of 400 U/ml of aspecific DNA/RNA endonuclease, 50 U/ml of endo-1,4-b-D-glucanase, and 0.06 U/ml of β-N-acetylhexosaminidase). 9ml of TGN or TGN containing antibiotics RIF/VAN (rifampicin 5µg/mL + vancomycin 8µg/mL) at clinically relevant concentrations found locally in bone or joints, was then added and the samples were incubated in identical conditions for 24h. The samples were then recovered and rinsed. CFU counts were obtained by recovering the bacteria with sonication, serial dilutions, and TSA plating. Biomass was determined via crystal violet staining, followed by dye solubilization in acetic acid, and absorbance measurement using a spectrophotometer. Results. Significant reductions in bacterial counts were observed in biofilms exposed to either RIF/VAN or RIF/VAN+CDD, by respectively 2,6 and 3,7Log10 when compared to samples reincubated with TGN alone (p <0.05). Additionally, CFU counts in samples exposed to RIF/VAN+CDD were reduced by 1,1Log10 when compared to those exposed to RIF/VAN (p<0,05). Significant reduction in biomass (-29,8%, p<0.05) was observed for coupons exposed to RIF/VAN+CDD when compared to C.D.D alone (figure 1). Conclusions. The concurrent utilization of enzymes with rifampicin and vancomycin, holds promise as a feasible method to address periprosthetic joint infections (PJIs). For any tables or figures, please contact the authors directly

Aim. This is the first study to directly compare the clinical outcome of debridement, antimicrobials and implant retention (DAIR) with stabilization using new internal fixation after debridement, for patients with Fracture-related Infection (FRI). Method. Consecutive patients with FRI Consensus confirmed FRI had single-stage surgery with tissue sampling, debridement, stabilization, antimicrobial therapy and skin closure. All cases had FRIs which were unhealed at surgery. When existing implants were stable, the implant was retained but loose implants or fractures with poor reduction had implant removal and refixation with new implants. All patients had the same empiric and definitive antibiotics, the same diagnostic criteria and outcome assessment at least one year after surgery. Failure was defined as infection recurrence, reoperation or lack of fracture consolidation at one year. Results. Seventy-one patients were studied (40 DAIRs and 31 new implants, including 10 exchange nails). The two groups were well matched for age, duration of infection, BACH complexity, microbiology, bone involved and need for flap coverage. Ten patients (13.7%) died before the endpoint. Mortality was similar in both groups (DAIR 14.1% vs New Metalware 12.9%; p=0.801) but DAIR of IM nails had a higher mortality at 40% (p=0.011). Sixty-one patients were followed-up for a mean of 3.32 years (1.04-9.43). Infection was eradicated in 23/34 (67.6%) DAIR patients and 24/27 (88.9%) with new metalware (p=0.049). Overall rates of infection-free union were similar in both groups (58.8% vs 77.8%; p=0.117). DAIR of plates had significantly fewer infection-free unions compared to removal and implantation of new plates (DAIR 57.1% vs NM 91.7%; p=0.033). Conclusion. Implantation of new metalware had better eradication of infection and a strong trend towards better union rates. Treating FRI with retained or new metalware had a substantial mortality (13.7%). Choosing DAIR did not reduce this mortality and these patients more often required further surgery to treat residual infection and secure union

Introduction. Since the expanded war in Ukraine in 2022, explosives, mines, debris, blast waves, and other factors have predominantly caused injuries during artillery or rocket attacks. These injuries, such as those from shelling shrapnel, involve high-energy penetrating agents, resulting in extensive necrosis and notable characteristics like soft tissue defects and multiple fragmentary fractures with bone tissue defects and a high rate of infection complications caused by multi resistant gram-negative (MRGN) pathogens. Material and Methods. We conducted a prospective study at our center between March 2022 and December 2023. Out of the 56 patients from Ukraine, 21 met the inclusion criteria who had severe war injuries were included in the study. Each of these patients presented with multiple injuries to both bones and soft tissues, having initially undergone treatment in Ukraine involving multiple surgeries. The diagnosis of infection was established based on the EBJIS criteria. Prior to our treatment patients had undergone multiple revision surgeries, including debridement, biopsies, implant and fixator replacement. Additionally, soft tissue management required previously VAC therapy and flap reconstruction for successful treatment. Results. All 21 infections manifested as bone infections (11; 52%), followed by implant-associated infections (5; 24%), soft tissue infections (4; 19%), and septic arthritis (1; 5%). In all patients, the infection was polymicrobial, caused by 3- and 4-MRGN pathogens, as Klebsiella pneumonia 4MRGN, Proteus mirabilis 4MRGN, Enterobacter cloacae 4MRGN etc. Upon admission, all patients carried a diagnosis and exhibited signs indicative of chronic infection. 19 (90.5%) patients required complex antibiotic regimens combined with multiple wound revisions and debridements, changes of fixators and combination of systemic and local antibiotic therapy. In 6 patients (28%) high dosages of local antibiotics such as gentamycin, vancomycin and meropenem were incorporated into a carrier of bio-absorbable calcium sulfate, calcium sulfate/hydroxyapatite which were introduced into the hip joint, femoral canal or bone defect for dead space management during the surgery. When local antibiotics were administered at intervals, the microbiology results at implantation showed negative results. 2 (9%) patients had new infections (different site, different pathogens), 1 (4.8%) is still under the treatment. In 17 (81%) patients infection complications were treated successfully with no recurrence of infection. Conclusion. War injuries result in complex bone and soft-tissue infections caused by 3-, 4-MRGN pathogens. Addressing this challenge necessitates multidisciplinary approach with multiple, thorough surgical debridements, effective local, and systemic antimicrobial therapy. As for the outlook we can see potential in local antibiotic carriers

Aims. Bone and joint infections cause significant morbidity, often requiring combination medical and surgical treatment. The presence of foreign material reduces the number of organisms required to cause an infection. The aim of this study was to assess whether there was a difference in the species of organism identified on culture in osteomyelitis compared to prosthetic joint infection. Method. This was a retrospective observational cohort study of patients that had surgical intervention for prosthetic joint infection or osteomyelitis with positive microbial culture between 2019 and 2022. Data including patient demographics, site of injury, BACH score for osteomyelitis and JS-BACH score for prosthetic joint infection, organism classification and antibiotic resistance to vancomycin and gentamicin were extracted from the medical record. Logistic and multiple regressions were used to adjust for potential confounding variables. Results. A total of 445 patients were included in the study; 267 patients with osteomyelitis or fracture-related infection and 177 patients with prosthetic joint infection. The patients with prosthetic joint infection were older (Mean age 70 for PJI; IQR 60-77 vs 56 for OM/FRI; IQR 39-64), more likely to be female (55.6% vs 26.2%) and had a higher BMI and ASA compared to those with osteomyelitis. Symptom duration tended to be longer in osteomyelitis/FRI (p<0.001). Staphylococcus aureus was the most common pathogen isolated in both osteomyelitis (155/267 (58.1%)) and prosthetic joint infection (85/177 (48.9%), followed by other Gram negative pathogens with 77/267 (28.8%) in osteomyelitis and 48/177 (27.1%) in prosthetic joint infection. On multivariate analysis, there was no difference between the rate of Staphylococcus aureus infection between the two groups. The rate of polymicrobial infection was higher in patients with osteomyelitis (92/267 (34.5%)) compared to prosthetic joint infection (38/177 (23.7%), however after adjustment for confounders there was no difference, p = 0.842. There was no difference in the presence of gentamicin resistant organisms or vancomycin resistant Gram positive organisms in osteomyelitis compared to prosthetic joint infection. Conclusion. Causative pathogens are similar in these two common forms of bone and joint infection. There was no significant difference in the identification, presence of polymicrobial infection or gentamicin and vancomycin resistance in organisms isolated in osteomyelitis compared to prosthetic joint infection. This may have implications for empiric antibiotic choice and local antibiotic therapy in the management of bone and joint infection

Aim. The primary objective is to evaluate the diagnostic performance of inoculating homogenized tissue and bone biopsies in blood culture bottles (BCB) for patients with (suspected) orthopaedic device-related infections. As secondary objective the time to positivity (TTP) of BCB and Wilkins-Chalgren broth (conventional method) will be evaluated. Method. Patients undergoing revision surgery due to suspected or proven fracture-related infection (FRI) or periprosthetic joint infection (PJI) according to respectively Consensus definition and EBJIS definition are included. 1,2. A minimal of three macroscopic infected/inflamed tissue/bone samples are collected in a container with saline and glass beads. 1.5 mL of the homogenized suspension is inoculated in BacT/ALERT FA and FN Plus bottles for 14 days. The remaining suspension is inoculated in Wilkins-Chalgren broth for 10 days and subcultured when cloudy or after 10 days. TTP is defined as the time until definite identification of the pathogen in the Laboratory Information System. Results. Up to now, 25 patients have been included, 11 (44%) had concordant results in BCB and the CM. In 11 patients cultures showed negative results for both methods. Three patients tested positive with BCB but remained negative with the same pathogen in CM. In the first patient, the CM failed to identify anaerobic bacteria (i.e. Fusobacterium nucleatum). In the second patient, three BCB were positive with Staphylococcus capitis. The third patient showed an infection with Escherichia coli, which was detected in all samples from the BCB, while all cultures obtained with the CM remained negative. A possible explanation for this discrepancy could be that this patient already received antibiotic therapy. BCB contain resins, which are capable of neutralizing antibiotic activity. Another case illustrating superiority of BCB involved an infection with Cutibacterium acnes, which showed positivity in six BCB, while only three were positive using the CM. We observed the shortest TTP with BCB. The median TTP of BCB was 32.0 hours (IQR 29.8) compared to a median TTP of 77.5 hours (IQR 107.6) when culturing with the CM. Contamination was seen in three patients with both methods, in eight patients contamination was only seen with the CM. For the remaining 14 patients no contamination was found. Conclusions. The results in this ongoing study indicate that the recovery of pathogens and TTP is better using BCB compared to CM. In addition, contamination occurs less frequently with the BCB method. Culturing tissue or bone biopsies in BCB seems a promising and faster detection method

Aim. Periprosthetic joint infections follow 1-3% of arthroplasty surgeries, with the biofilm nature of these infections presenting a significant treatment challenge. 1. Prevention strategies include antibiotic-loaded bone cement; however, increases in cementless procedures means there is an urgent need for alternative local antimicrobial delivery methods. 2. A novel, ultrathin, silica-based sol-gel technology is evaluated in this research as an anti-infective coating for orthopaedic prosthetic devices, providing local antibiotic release following surgery. Method. Reduction in clinically relevant microbial activity and biofilm reduction by antimicrobial sol-gel coatings, containing a selection of antibiotics, were assessed via disc diffusion and microdilution culture assays using the Calgary biofilm device. 3. Proliferation, morphology, collagen, and calcium production by primary bovine osteoblasts cultured upon antibiotic sol-gel surfaces were examined, and cytotoxicity evaluated using Alamar blue staining and lactate dehydrogenase assays. Concentrations of silica, calcium and phosphorus compounds within the cell layer cultured on sol-gel coatings and concentrations eluted into media, were quantified using ICP-OES. Furthermore, cellular phenotype was assessed using alkaline phosphatase activity with time in culture. Results. Low antibiotic concentrations within sol-gel had an inhibitory effect on clinically relevant biofilm growth, for example 0.8 mg ml. -1. tobramycin inhibited clinically isolated S. aureus (MRSA) growth with an 8-log reduction in viable colony forming units. There was no significant difference in metabolic activity between untreated and sol-gel exposed primary bovine osteoblasts in elution-based assays. Reduction (2-fold) in metabolic activity in direct contact assays after 48 hours exposure was likely to be due to increased osteoinduction, whereas no impact upon cell proliferation were observed (p=0.92 at 14 days culture). The morphology of primary osteoblasts was unaffected by culture on sol-gel coatings and collagen production was maintained. Calcium containing nodule production within bovine osteoblastic cells was increased 16-fold after 14 days culture upon sol-gel. Conclusions. The ultrathin sol-gel coating showed low cytotoxicity, strong biofilm reducing activity and antimicrobial activity, which was comparable to antibiotics alone, demonstrating that sol-gel delivery of antibiotics could provide local antimicrobial effects to inhibit PJI growth without the need for bone cement. Future work will develop and evaluate sol-gel performance in an ex vivo explant bone infection model which will reduce the need for animal experimentation

Aim. Periprosthetic joint infection (PJI) is one of the most serious and frequent complications in prosthetic surgery. Despite significant improvements in the criteria for diagnosis of PJI, the diagnostic workflow remains complex and, sometimes, inconclusive. Host immune factors hold great potential as diagnostic biomarkers in bone and joint infections. We have recently reported that the synovial concentration of the humoral pattern recognition molecule long pentraxin 3 (PTX3) is a sensitive and specific marker of PJI in total hip and knee arthroplasty patients (THA and TKA) undergoing revision surgery [1]. However, the contribution to risk and diagnosis of PJI of the genetic variation in PTX3 and inflammatory genes that are known to affect its expression (IL-1b, IL-6, IL-10, and IL-17A) has not been addressed. Therefore, we assessed these relationships in a cohort of THA and TKA patients who underwent prosthesis revision by focusing on a panel of single nucleotide polymorphisms (SNPs) in the PTX3, IL-1β, IL-6, IL-10 and IL-17A genes. Method. A case-control retrospective study was conducted on an historic cohort of patients that received THA or TKA revision and were diagnosed with PJI (cases) or aseptic complications (controls) [1]. Samples of saliva were collected from 93 subjects and used for extraction of genomic DNA to perform genotyping of the PTX3, IL-1β, IL-6, IL-10 and IL-17A polymorphisms. Moreover, whenever available, samples of synovial fluid and plasma [1] were used to measure the concentration of the IL-1β, IL-10, and IL-6 proteins by immunoassay. Uni-and multivariate analyses were performed to evaluate the relationships between genetic, biochemical, and clinical variables. Results. The rs3024491 (IL-10) and rs2853550 (IL-1b) SNPs were found to be strongly associated with the risk of PJI. The synovial levels of PTX3, IL-1β, IL-10, and IL-6 were higher in cases than in controls, and a clear correlation emerged between the synovial concentration of PTX3 and IL-1b in cases only. Also, we identified a causal relationship between rs2853550, synovial concentration of IL-1b and that of PTX3 (that is induced by IL-1b). Conclusions. Our findings suggest that SNPs in the IL-10 and IL-1b genes could be used for early identification of THA and TKA patients with high risk of PJI. It is therefore conceivable that integrating genetic data into current diagnostic criteria would improve diagnosis of PJI

Aim. Periprosthetic joint infection (PJI) is a devasting complication after total hip arthroplasty. Joint aspiration and preoperative biopsy can be helpful diagnostics for PJI. The aim of this study is to evaluate the diagnostic value of preoperative biopsies after inconclusive or dry tap aspiration of the hip in patients undergoing revision hip arthroplasty. Secondarily we will evaluate the diagnostic value of synovial fluid aspiration cultures and peroperative tissue cultures for diagnosing or ruling out PJI. Methods. Patients who underwent diagnostic aspiration and subsequent preoperative biopsy and/or revision surgery between January 2015 and January 2024 were included in the study. Synovial fluid aspirations and tissue samples obtained from biopsy and revision surgery were interpreted using the European Bone and Joint Infection Society criteria for PJI and in close consultation with the microbiologist. Results. 207 Patients were included with 231 synovial fluid aspirations. Sensitivity and specificity of synovial fluid aspiration cultures were 76% and 98%. In 62 patients tissue biopsies were performed, of which 40 after a dry tap. The tissue biopsies after a dry tap aspiration had a sensitivity of 50.0% and a specificity of 95.8%. In 21% tissue biopsies led to the confirmation of PJI in patient with a high suspicion of PJI after dry tap aspiration. In patients with an inconclusive synovial fluid aspiration result the addition of tissue biopsies led to a change in treatment in 14%. In 212 cases revision surgery was performed, intraoperative tissue cultures had a sensitivity and specificity of 83.3% and 99.3%. Conclusions. Diagnosing PJI can be troublesome, especially if synovial fluid aspiration provides a dry tap. Tissue biopsy cultures in patients with a high suspicion of PJI after dry tap aspiration is a feasible way to confirm PJI, in 21% of patients PJI could be confirmed after dry tap aspiration. Ruling out PJI by means of a biopsy after a dry tap aspiration is less successful due to its low sensitivity. Tissue biopsies after an inconclusive aspiration leads to clinically important treatment changes

Aim. Bone infections often manifest with soft tissue complications such as severe scarring, fistulas, or ulcerations. Ideally, their management involves thorough debridement of infected bone and associated soft tissues, along with achieving stable bone structure, substantial tissue coverage, and long-term antibiotic therapy. The formation of a multidisciplinary team comprising orthopedic surgeons, plastic surgeons, and infectious disease specialists is essential in addressing the most complex cases. Method. We conducted a retrospective study during six years (2018-2023) at our university center. Focusing on the most challenging cases, we included patients with bone infections in the leg and/or foot requiring free flap reconstruction. Each patient underwent simultaneous bone debridement and reconstruction by the orthopedic team, alongside soft tissue debridement and free flap reconstruction by the plastic surgery team. Targeted antibiotic therapy for either 6 weeks (acute) or 12 weeks (chronic osteitis) was initiated based on intraoperative cultures. Additional procedures such as allografts, arthrodesis, or autografts were performed if necessary. We analyzed the rates of bone union, infection resolution, and limb preservation. Results. Forty-five patients were enrolled. Twenty-four patients (53.3%) had urgent indications (e.g., open infected fractures, osteitis, acute osteoarthritis, or wound dehiscence), while 21 (46.7%) underwent elective surgery (e.g., septic pseudarthrosis or chronic osteitis). Two patients underwent amputation due to flap failure (4.4%), and one patient was lost to follow-up. Follow-up of the remaining 42 patients averaged 28 months (range: 6–60 months). During this period, 35 patients (83.4%) experienced no recurrence of infection. Similarly, 35 patients (83.4%) achieved bone union. Overall, the rate of lower limb preservation was 93.3%. Conclusions. Managing bone infection coupled with soft tissue defects brings significant challenges. Although the majority of patients treated here belong to a complex framework based on the BACH classification, the outcomes achieved here appear to align with those of the simpler cases, thanks to optimal care with a dedicated septic ortho-plastic team. Our study demonstrates a notable success rate in treating infection, achieving bone consolidation, and preserving lower limb function

Aim. Prosthetic joint infections (PJI) are a common reason for revisions in patients that underwent total arthroplasty of the hip (THA) or knee (TKA). Extensive antibiotic treatment follows while a clear understanding of target site concentrations is lacking. The aim is to investigate the target site concentrations, like bone and synovial tissue concentrations, which consequently may lead to an optimisation of the dosing regiments of cefuroxime of PJI patients suffering from pain and immobility. Dosing optimisation may lead to a reduced risk of (re-)infection and adverse effects like renal-insufficiency and therefore lower health-care costs. Method. Patients (n=26) with PJI of hip or knee undergoing a one- or two-stage revision treated with cefuroxime were included as part of the ASTERICS study. During implant removal two samples were collected 15-30 and 60-120 minutes after IV infusion of plasma, bone tissue and synovial tissue and one synovial fluid sample. Samples were analysed using a UltraPerformance Convergence Chromotography – quadruple mass spectrometry system (UPC. 2. -MS/MS). Bone tissue and synovial tissue were pulverized before analysis acquiring for bone tissue a homogenate of cortical and cancellous bone. Using nonlinear mixed effect modelling (NONMEM) a base model was developed to analyse the bone to plasma ratio of cefuroxime in osteomyelitis patients. Results. Mean bone concentrations (mg/L) of cefuroxime at 30-60 min after IV administration in the knee and hip are 21.29 (SD:11.86) and 19.06 (SD: 11.79) respectively and 8.23 (SD:4.90) and 9.67 (SD:9.75) respectively at 90-120 min after IV administration. The penetration of cefuroxime described by the bone:plasma ratio into knee and hip affected by osteomyelitis is 0.3 and 0.4 respectively within 1 hour and 0.1 for both joints within 2 hours. The results mentioned here were collected during knee operations without blood void conditions. Concentration data was used to develop a base pharmacokinetic model using NONMEM and was best described by a two-compartment model. Conclusions. Cefuroxime penetrates osteomyelitis affected bone tissue within the hour proving the usefulness of cefuroxime as prophylaxis of orthopaedic surgery and as treatment option for PJI. However, PK modelling and further simulations need to prove whether repeated cefuroxime dosing in this population is required to reach minimal inhibitory concentrations in target tissue

Aim. Diagnosing low-grade periprosthetic joint infections (PJI) can be very challenging due to low-virulent microorganisms capable of forming biofilm. Clinical signs can be subtle and may be similar to those of aseptic failure. To minimize morbidity and mortality and to preserve quality of life, accurate diagnosis is essential. The aim of this study was to assess the performance of various diagnostic tests in diagnosing low-grade PJI. Methods. Patients undergoing revision surgery after total hip and knee arthroplasty were included in this retrospective cohort study. A standardized diagnostic workup was performed using the components of the 2021 European Bone and Joint Infection Society (EBJIS) definition of PJI. For statistical analyses, the respective test was excluded from the infection definition to eliminate incorporation bias. Receiver-operating-characteristic curves were used to calculate the diagnostic performance of each test, and their area-under-the-curves (AUC) were compared using the z-test. Results. 422 patients undergoing revision surgery after total hip and knee arthroplasty were included in this study. 208 cases (49.3%) were diagnosed as septic. Of those, 60 infections (28.8%) were defined as low-grade PJI (symptoms >4 weeks and caused by low-virulent microorganisms (e. g. coagulase-negative staphylococci, Cutibacterium spp., enterococci and Actinomyces)). Performances of the different test methods are listed in Table 1. Synovial fluid (SF) - WBC (white blood cell count) >3000G/L (0.902), SF - %PMN (percentage of polymorphonuclear neutrophils) > 65% (0.959), histology (0.948), and frozen section (0.925) showed the best AUCs. Conclusion. The confirmatory criteria according to the EBJIS definition showed almost ideal performances in ruling-in PJI (>99% specificity). Histology and synovial fluid cell count (SF-WBC and SF-%PMN) showed excellent accuracies for diagnosing low-grade PJI. However, a reduced immune reaction in these cases may necessitate lower cut-off values. Intraoperative frozen section may be valuable in cases with inconclusive preoperative diagnosis. For any tables or figures, please contact the authors directly