Introduction. Identification of the causative pathogen in musculoskeletal infection is critical as it directs further treatment. Fracture-related infection is often associated with ‘no growth’ in standard culture. We investigated the efficiency of two alternate methods to identify the causative pathogen, namely extended bacterial culture and 16Sr RNA gene sequence analysis with next generation sequencing (NGS) in ‘culture negative’ fracture related infections. Method. Patients were diagnosed as having fracture related infection based on the MSIS criteria (n=120). All patients had samples taken for culture and sensitivity. All samples which were culture negative by standard culture methods formed the study group. These samples were subjected to further extended culture in both aerobic and anaerobic medium for 14 days to improve recovery of pathogens. Further, DNA isolated from implants from a sub-group of these culture negative patients were subjected to 16SrRNA gene amplification followed by Sanger sequencing. Subsequent sequencing analysis was performed using the Illumina NGS platform which identified and detected the most abundant genera/species present in those samples more precisely. Result. 57 culture negative samples formed the study group. Eight samples (14%) converted to positivity after 14 days of culture. Bacteroides fragilis was the commonest yield. 14 samples underwent 16SrRNA gene amplification followed by Sanger sequencing. Acinetobacter baumannii, Enterococcus faecalis, Pseudomonas aeruginosa were identified as common pathogens. Next generation sequencing (n=12) not only identified common pathogens like as Staphylococcus, Acinetobacter baumannii, but also many uncultivable species. Conclusion. Positive results from extended bacterial culture are about 15%. The delay in definite identification of pathogens in extended culture may be critical in certain clinical situations. Molecular methods are quicker and have additional yield in culture negative infections. The exact role of all microorganisms identified by molecular methods in the pathogenesis of infection is unknown

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The efficacy of saline irrigation for treatment of implant-associated infections is limited in the presence of porous metallic implants. This study evaluated the therapeutic efficacy of antibiotic doped bioceramic (vancomycin/tobramycin-doped polyvinyl alcohol composite (PVA-VAN/TOB-P)) after saline wash in a mouse infection model implanted with titanium cylinders.

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This aim of this study was to analyze the detection rate of rare pathogens in bone and joint infections (BJIs) using metagenomic next-generation sequencing (mNGS), and the impact of mNGS on clinical diagnosis and treatment.

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The aim of the present study was to assess the outcomes of the induced membrane technique (IMT) for the management of infected segmental bone defects, and to analyze predictive factors associated with unfavourable outcomes.

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Metal particles detached from metal-on-metal hip prostheses (MoM-THA) have been shown to cause inflammation and destruction of tissues. To further explore this, we investigated the histopathology (aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) score) and metal concentrations of the periprosthetic tissues obtained from patients who underwent revision knee arthroplasty. We also aimed to investigate whether accumulated metal debris was associated with ALVAL-type reactions in the synovium.

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

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Fracture-related infection (FRI) is commonly classified based on the time of onset of symptoms. Early infections (< two weeks) are treated with debridement, antibiotics, and implant retention (DAIR). For late infections (> ten weeks), guidelines recommend implant removal due to tolerant biofilms. For delayed infections (two to ten weeks), recommendations are unclear. In this study we compared infection clearance and bone healing in early and delayed FRI treated with DAIR in a rabbit model.

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To investigate the efficacy of ethylenediaminetetraacetic acid-normal saline (EDTA-NS) in dispersing biofilms and reducing bacterial infections.

The December 2023 Foot & Ankle Roundup³⁶⁰ looks at: Subchondral bone cysts remodel after correction of varus deformity in ankle arthritis; 3D-printed modular endoprosthesis reconstruction following total calcanectomy; Percutaneous partial bone excision in the management of diabetic toe osteomyelitis; Hemiepiphysiodesis is a viable surgical option for Juvenile hallux valgus; Ankle arthroplasty vs arthrodesis: which comes out on top?; Patient-related risk factors for poorer outcome following total ankle arthroplasty; The Outcomes in Ankle Replacement Study.

Aim. At our tertiary orthopaedic centre, mycobacterial cultures are routinely performed on bone and joint samples sent for bacterial culture. We have previously described the prevalence Mycobacterium tuberculosis Complex (MTBC) in these samples. Here, we describe the prevalence of non-tuberculous mycobacteria (NTM). We calculate the number needed to test to identify one previously undiagnosed mycobacterial bone or joint infection. Methods. Samples taken during a single procedure were pooled in one BACTEC MGIT culture. From laboratory records, we ascertained the number of mycobacterial cultures performed, the number positive for MTBC or NTM, and characteristics of individuals from whom mycobacteria were isolated. We collected the same data from 100 individuals with negative mycobacterial cultures. Results presented here are from interim analysis. Results. Excluding sample types that were clearly not bone or joint samples, 6162 mycobacterial cultures were performed between 4 July 2017 and 30 September 2022. Twenty-two patients had MTBC and 6 patients had NTM newly isolated from bone or joint samples placed in mycobacterial culture, with a further patient having both M. tuberculosis and M. avium isolated. In both patients with M. abscessus, the organism also grew in routine bacterial cultures. In one further patient, M. fortuitum was isolated from a sample not put into mycobacterial culture. To identify one new mycobacterial infection of bone or joint (MTBC or NTM) that would not be detected with routine bacterial cultures, 228 (95% CI 157 – 346) mycobacterial cultures were needed. The laboratory cost per additional patient identified using MGIT cultures was €12,540 (95% CI €8,635 - €19,030). Mycobacterial cultures were much less likely to be positive in samples taken from prosthetic joints. They were more likely to be positive in spinal samples and in samples taken from patients with suspected sarcoma. In patients for whom we had contemporaneous histological specimens, these demonstrated granulomatous inflammation in 86% (18/21) of patients from whom MTBC had been isolated but in neither of the two patients from whom only NTM was isolated. Ascertaining the clinical significance of NTM isolates is challenging, although in 2/8 cases the same organism was isolated following repeat sampling. Conclusions. Targeted rather than routine mycobacterial culture of bone and joint specimens should be considered in settings with a low burden of tuberculosis. NTM are rarely isolated from bone and joint specimens at our centre and fast growers may be isolated using routine bacterial culture

Aim. Differentiation of infected (INF) nonunion from aseptic (AS) nonunion is crucial for the choice of intra- and postoperative treatment. Preoperative diagnosis of infected nonunion is challenging, especially in case of low-grade infection lacking clinical signs of infection. Standard blood markers such as C-reactive protein or leucocyte count do not aid in preoperative diagnosis. Proteomic profiling has shown promising results for differentiation of numerous chronic disease states, and in this study was applied to preoperative blood samples of patients with nonunion in an attempt to identify potential biomarkers. Method. This prospective multicenter study enrolled patients undergoing revision surgery of femur or tibia nonunion. Patients with implant removal after regular fracture healing (HEAL) were included as a control-group. Preoperative blood samples, intraoperative tissue samples, sonication of osteosynthesis material and 1-year-follow-up questionnaire were taken. Nonunion patients were grouped into INF or AS after assessing bacterial culture and histopathology of retrieved samples. Diagnosis of infection followed the fracture related infection consensus group criteria, with additional consideration of healing one year after revision surgery. Targeted proteomics was used to investigate a predefined panel of 45 cytokines in preoperative blood samples. Statistical differences were calculated with Kruskal Wallis and Dunn's post hoc test. Cytokines with less than 80% of samples being above the lower limit of detection range (LLDR) were excluded for this study. Results. We recruited 62 AS, 43 INF and 32 HEAL patients. Patients in the two nonunion groups (INF and AS) did not differ concerning smoking, diabetes or initial open or closed fracture. Thirty-two cytokines were above LLDR in >80% of patients. INF patients showed a significant difference in expression of 8 cytokines compared to AS, with greatest differences observed for Macrophage Colony Stimulating Factor 1 (MCSF-1) and Hepatocyte Growth Factor (HGF) (p<0.01). In comparing AS with HEAL patients, 9 cytokines displayed significant differences, including interleukin (IL)-6, Vascular Endothelial Growth Factor A (VEGFA), Matrix Metalloproteinase 1 (MMP-1). Comparison of INF with HEAL patients revealed significantly different expression of 20 cytokines, including. IL-6, IL-18, VEGFA or MMP-1. Conclusions. Our study revealed differences in plasma cytokine profile of blood samples from INF and AS patients. Although no single biomarker is sufficient to differentiate these patients preoperatively in isolation, future multivariant analysis of this cytokine data in combination with clinical characteristics may provide valuable diagnostic insights. Funded by German Social Accident Insurance (FF-FR 0276) and AO Trauma (AR2021_04)

Aim. Surgical treatment of ankle fractures comes with a substantial risk of complications, including infection. An unambiguously definition of fracture-related infections (FRI) has been missing. Recently, FRI has been defined by a consensus group with a diagnostic algorithm containing suggestive and confirmatory criteria. The aim of the current study was to report the prevalence of FRI in patients operated for ankle fractures and to assess the applicability of the diagnostic algorithm from the consensus group. Method. Records of all patients with surgically treated ankle fractures from 2015 to 2019 were retrospectively reviewed for signs of postoperative infections. Patients with suspected infection were stratified according to confirmatory or suggestive criteria of FRI. Rate of FRI among patients with confirmatory and suggestive criteria were calculated. Results. Suspected infection was found in 104 (10%) out of 1004 patients. Among those patients, confirmatory criteria were met in 76/104 (73%) patients and suggestive criteria were met in 28/104 (27%) at first evaluation. Patients with clinical confirmatory criteria (N= 76) were diagnosed with FRI. Patients with suggestive criteria were further examined with either bacterial sampling at the outpatient clinic, revision surgery including bacterial sampling, or a wait-and-see approach. Eleven (39%) of the 28 patients had positive cultures and were therefore diagnosed as having FRI at second evaluation. In total 87 (9%) patients were diagnosed with FRI according to the consensus definition. Only 73 (70%) of the 104 patients with suspected FRI had adequate bacterial sampling. Conclusions. The prevalence of FRI, applying the FRI-consensus criteria, for patients with surgically treated ankle fractures was 9%. Twenty-two percent of patients who met the confirmatory criteria had negative bacterial cultures. The current study shows that we did not have a systematic approach to patients with suspected FRI as recommended by the consensus group. A systematic approach to adequate bacterial sampling when FRI is suspected is paramount. The consensus definition of FRI and its diagnostic algorithm facilitates such an approach

The August 2023 Foot & Ankle Roundup³⁶⁰ looks at: Achilles tendon rupture: surgery or conservative treatment for the high-demand patient?; First ray amputation in diabetic patients; Survival of ankle arthroplasty in the UK; First metatarsophalangeal joint fusion and flat foot correction; Intra-articular corticosteroid injections with or without hyaluronic acid in the management of subtalar osteoarthritis; Factors associated with nonunion of post-traumatic subtalar arthrodesis; The Mayo Prosthetic Joint Infection Risk Score for total ankle arthroplasty.

Irrigation with antiseptic agents, antibiotics, and surfactants are used for treatment and prevention of infections. Despite desirable microbicidal actions, studies have demonstrated cytotoxic effects on host tissue that may impair healing. This study investigated the extent of tissue damage caused by commonly used irrigation solutions in the presence or absence of infection. Air pouches created in 60 balb/c mice were divided into two groups (n=30): infected with Staphylococcus aureus and control. One week later the infected group was subdivided into 5 subgroups (n=6) based on irrigation solutions and by day 0 (immediately) and day7 after irrigation (n=3). Solutions included Saline, Bacitracin, Clorpactin, Irrisept and Bactisure. In infected group wash fluid was collected for quantitative analysis of bacterial growth. At the specified times mice were sacrificed, pouch tissue sent for histology, and sections analyzed for inflammation, necrosis, and edema. Inflammation decreased in infected vs sterile pouches for all solutions except Bacitracin day 0 and for all solutions day 7 with significance in all except Bacitracin (p<0.05). On day 0, necrosis increased in infected vs sterile pouches in Bacitracin (p=0.006), Irrisept (p=0.18), or Bactisure (p=0.07); however, on day 7, necrosis significantly decreased in infected pouches for all solutions (p<0.05) except for Clorpactin (p=0.18). Edema decreased in infected vs sterile pouches on day 0 for all solutions with significance in saline, Irrisept, and Bacitracin (p<0.05). On day 7, infected pouches had decreased edema in saline, Bacitracin, and Bactisure (p<0.05) and increased in Irrisept (p<0.05) and Clorpactin (p=0.069) compared to sterile pouches. Bacterial culture of washouts demonstrated that Clorpactin, Irrisept and Bactisure controlled the infection, whereas saline and Bacitracin showed bacterial multiplication 3.9 × 10^7 CFU/ml and 6.7 × 10^7 CFU/ml respectively. Bacitracin wash showed significantly more bacteria growth compared to Clorpactin (p=0.024), Irrisept (p=0.025) and Bactisure (p=0.025). Tissue damage varied with irrigation solutions and the presence or absence of infection. Presence of bacteria appeared to lead to less tissue inflammation and edema. Tissue necrosis varied over time with different solutions. Surgeons must weigh risks and benefits when selecting solutions and determining when to irrigate

Aims

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

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The aim of this study was to evaluate the optimal deep tissue specimen sample number for histopathological analysis in the diagnosis of periprosthetic joint infection (PJI).

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Arthroplasty surgery of the knee and hip is performed in two to three million patients annually. Periprosthetic joint infections occur in 4% of these patients. Debridement, antibiotics, and implant retention (DAIR) surgery aimed at cleaning the infected prosthesis often fails, subsequently requiring invasive revision of the complete prosthetic reconstruction. Infection-specific imaging may help to guide DAIR. In this study, we evaluated a bacteria-specific hybrid tracer (^99mTc-UBI_29-41-Cy5) and its ability to visualize the bacterial load on femoral implants using clinical-grade image guidance methods.

Aim. A novel anti-infective biopolymer implant coating was developed to prevent bacterial biofilm formation and allow on-demand burst release of anti-infective silver (Ag) into the surrounding of the implant at any time after surgery via focused high-energy extracorporeal shock waves (fhESW). Method. A semi-crystalline Poly-L-lactic acid (PLLA) was loaded with homogeneously dissolved silver (Ag) applied onto Ti6Al4V discs. A fibroblast WST-1 assay was performed to ensure adequate biocompatibility of the Ag concentration at 6%. The prevention of early biofilm formation was investigated in a biofilm model with Staphylococcus epidermidis RP62A after incubation for 24 hours via quantitative bacteriology. In addition, the effect of released Ag after fhESW (Storz DUOLITH SD1: 4000 impulses, 1,24 mJ/mm. 2. , 3Hz, 162J) was assessed via optical density of bacterial cultures (Escherichia coli TG1, Staphylococcus epidermidis RP62A, Staphylococcus aureus 6850) and compared to an established electroplated silver coating. The amount of released Ag after the application of different intensities of fhESW was measured and compared to a control group without fhESW via graphite furnace atomic absorption spectrometry (GF-AAS), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). Results. The coating with 6% Ag reduced Staphylococcus epidermidis biofilm formation by 99.7% (mean±SD: 2.1×10^5 ± 3,9×10^5 CFU/µL) compared to uncoated controls (6.8×10^7 ± 4.9×10^7 CFU/µL); (p=0.0001). After applying fhESW the commercially available electroplated silver coating did not prevent the growth of all tested bacterial strains. Bacterial growth is delayed with 4% Ag and completely inhibited with 6% Ag in the novel coating, except for a small increase of S. aureus after 17 hours. SEM and EDS confirmed a local disruption of the coating after fhESW. Conclusions. This novel anti-infective implant coating has the potential to prevent bacterial biofilm formation. The on-demand burst release of silver via fhESW could be an adjunctive in the treatment of implant related infection and is of particular interest in the concept of single stage revision surgery

Aim. In recent years, many studies on revision for infection after arthroplasty have been published. In national arthroplasty registers, revision for infection is defined as surgical debridement, with or without removal or exchange of the entire or parts of the prosthesis due to deep infection, and should be reported to the register immediately after surgery. The diagnosis of infection is made at the surgeon's discretion, based on pre- and perioperative assessment and evaluation, and is not to be corrected to the register based on peroperative bacterial cultures. Due to this lack of validation, the rate of revision for infection will only be an approximation of the true rate of periprosthetic joint infection (PJI). Our aim was to validate the reporting of infection after total hip arthroplasty, and to assess if revisions for infection actually represented true PJI. Methods. We investigated the reported revisions for infection and aseptic loosening after total hip arthroplasty from 12 hospitals, representing one region of the country, reported during the period 2010–2020. The electronic patient charts were investigated for information on surgical treatment, use of antibiotics, biochemistry and microbiology findings. PJI was defined as growth of at least two phenotypically identical microbes in perioperative tissue samples. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated. Results. 145 revisions for infection and 137 revisions for aseptic loosening were reported. Of the reported infections, there were 141/145 true positives and 4/145 false positives. Of the reported aseptic loosenings, there were 126/137 true negatives and 11/137 false negatives. This gives a positive predictive value of 0.97, negative predictive value of 0.92, sensitivity of 0.93, specificity of 0.97 and accuracy of 0.95. Interpretation. We found the reporting revision for infection after total hip arthroplasty to the national register accurate. There was high correlation between reported revision for infection and PJI. Studies on revision for infection from arthroplasty registers may therefore be considered as reliable as studies of true PJI

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We aimed to evaluate the utility of ⁶⁸Ga-citrate positron emission tomography (PET)/CT in the differentiation of periprosthetic joint infection (PJI) and aseptic loosening (AL), and compare it with ^99mTc-methylene bisphosphonates (^99mTc-MDP) bone scan.