Septic Arthritis Research Articles

Extrapulmonary Mycobacterium abscessus Infections, France, 2012-20201.

Mycobacterium abscessus infection is challenging to treat. Extrapulmonary M. abscessus infections (EP-MAB) are less common than pulmonary M. abscessus infections. To evaluate treatment regimens, we retrospectively analyzed consecutive microbiologically confirmed EP-MAB cases diagnosed in France during 2012-2020. We studied 45 patients with EP-MAB, including 14 bone and joint infections, 10 skin and soft tissue infections, and 8 lymph node infections. Most (62%) patients had no reported immunodeficiency. In 27 patients, EP-MAB followed healthcare-associated (44%) or environmental (16%) injuries. Of the 45 isolates, 25 were subspecies abscessus, 10 bolletii, and 9 massiliense; 1 was unidentified. Cure was achieved for 36 (80%) patients who received a median antimicrobial regimen of 6 months; 22 (55%) also underwent surgery. Four patients died, and 5 were unavailable for follow-up. EP-MAB predominantly affects immunocompetent patients after an injury; outcomes are favorable. We propose a >6-month regimen of antimicrobial therapy with consideration for surgery and regular patient reassessment.

Local Delivery of Exosomes and Antibiotics in Hydroxyapatite-Based Nanocement for Osteomyelitis Management.

The management of bone and joint infections is a formidable challenge in orthopedics and poses a global health concern. While clinical management emphasizes infection prevention and complete eradication, an effective strategy for stabilizing skeletal tissue with adequate soft tissue coverage remains limited. In this study, we have employed a novel approach of using the local delivery of exosomes and antibiotics (rifampicin) using a hydroxyapatite-based nanocement carrier to manage the residual space created during debridement effectively. Additionally, we synthesized a periosteum-guiding antioxidant herbal membrane to leverage the inherent periosteum regeneration capability of the bone, facilitating bone callus repair and natural healing. The synthesized scaffolds were biocompatible and demonstrated potent antibacterial activity in vitro. When evaluated in vivo in the Staphylococcus aureus-induced rat tibial osteomyelitis model, the released drugs successfully cleared the residual bacteria and the released exosome promoted bone healing, resulting in 3-fold increase in bone volume as analyzed via micro-CT analysis. Immunofluorescence staining of periosteum-specific markers also indicated the complete formation of periosteal layers, thus highlighting the complete bone repair.

Improving the microbiological diagnosis of fracture-related infection and prosthetic joint infection through culturing sonication fluid in Bactec blood culture bottles.

Sonication of surgically removed implants appears to optimize the microbiological diagnosis in orthopedic implant-associated infections (OIAI). However, reports of infection with negative cultures can still reach high rates. A study evaluating the inoculation of sonication fluid into blood culture bottles (SFBCB) in patients with fracture-related infection (FRI) and prosthetic joint infection (PJI) is necessary. This study compared the accuracy SFBCB over the conventional sonication fluid cultures (CSFC) and tissue culture (TC). Consecutive patients who underwent implant removal surgeries due to any reason had their implants sonicated according to standardized method. Definitions of PJI and FRI were based upon criteria by European Bone and Joint Infection Society (EBJIS) and Metsemakers, respectively. Between three to five intraoperative tissue samples were processed. The implant`s sonication fluid was seeded onto sheep blood agar, chocolate agar, thioglycolate broth and on tryptic soy broth for CSFC, while was also inoculated into blood culture bottles and incubated in the automated system during 5 days for SFBCB. Overall, 74 patients were analyzed, of which 57 with OIAI (48 FRI and 09 PJI) and 17 aseptic failures (03 arthroplasties and 14 osteosynthesis). Interestingly, SFBCB demonstrated significantly higher sensitivity compared to CSFC (96.5% [95% CI, 88-100] vs. 78.9% [95% CI, 66-89], p = 0.004), and to TC (96.5% [95% CI, 88-100], vs. 57.9% [95% CI, 44-71], p < 0.001), whereas there were no significant differences in specificity between the three methods. In comparison to CSFC and TC, SFBCB improved sensitivity for diagnosing OIAI without compromising specificity.

Isolation and characterisation of novel lytic bacteriophages for therapeutic applications in biofilm-associated prosthetic joint infections

Abstract Prosthetic joint infections are devastating complications of joint arthroplasties. Without effective management, they can lead to limb amputation and even death. A significant proportion of these infections is caused by the primarily commensal Coagulase-negative Staphylococci pathogens, which form thick, antibiotic-resistant biofilms at the site of infection. Combinatorial therapy involving antibiotics and bacteriophages may represent a strategy to overcome resistance. Previous research indicates that as bacteria develop resistance to antibiotics, they often become more susceptible to bacteriophages. In this study, we produced a cocktail of novel bacteriophages and assessed their viability to eradicate nosocomial staphylococcal biofilms. Here, we used clinical isolates from prosthetic joint infections to isolate and identify four new bacteriophages from sewage effluent. These novel phages were characterized through electron microscopy and full genome sequencing. Subsequently, we combined them into a phage cocktail, which effectively re-sensitized biofilms to vancomycin and flucloxacillin. Notably, this phage cocktail demonstrated low cytotoxicity in vitro to human epithelial cells, even when used alongside antibiotic treatments. These findings highlight the potential of the phage cocktail as a tool to increase antibiotic treatment success in prosthetic joint infections.

Hospitalisation cost for paediatric osteomyelitis and septic arthritis in New Zealand.

Hospitalisation rates for paediatric bone and joint infection (BJI) in New Zealand (NZ) are among the highest globally. This study aims to quantify hospitalisation costs of BJI in 2018-2019. National hospitalisation data from the NZ Ministry of Health was used to describe costs associated with all paediatric hospitalisations coded for osteomyelitis or septic arthritis in those aged <16 years. Data included age, ethnic group, area level deprivation, diagnosis-related-group coding, admission length and cost-weight. Readmissions up to 24 months following the initial encounter were analysed for associated costs. More than ten million dollars was spent on hospitalisation for paediatric BJI over the study period (NZ$10 819 474). There were 869 primary hospitalisations and 229 related readmissions. Median length of stay was 7.4 days (95% confidence interval 6.8-7.9). Re-admission costs were NZ$1 196 640 within 24 months following diagnosis. Higher median hospitalisation costs occurred for children residing in the most deprived versus least deprived neighbourhoods (NZ$12 126 vs. NZ$9010, P < 0.01). NZ Māori compared with non-Māori children had longer length of stay (8.4 vs. 6.3 days, P = 0.04), more complex and severe illnesses (53% vs. 17%, P < 0.01), and higher median hospitalisation costs (NZ$11 796 vs. NZ$9581, P = 0.03). Direct BJI hospitalisation costs in 2018-2019 were NZ$10 819 474 with 11% of costs due to re-admission. Direct hospitalisation costs for paediatric BJI in NZ vary by deprivation and ethnic group. Illness complexity of paediatric BJI varies by ethnic group. Interventions are needed to reduce incidence and severity of these debilitating infections.

Influence of Diabetes Mellitus on Postoperative Complications After Total Knee Arthroplasty: A Systematic Review and Meta-Analysis

Background and Objectives: Total knee arthroplasty (TKA) is an effective treatment option for severe knee osteoarthritis. Understanding the impact of diabetes mellitus (DM) on postoperative outcomes is crucial for improving patient satisfaction after TKA. This study aimed to investigate the influence of DM on postoperative complications and mortality after TKA. Materials and Methods: We conducted a systematic review and meta-analysis by searching relevant studies published before December 2023 in the PubMed, EMBASE, Cochrane Library, Medline, and Web of Science databases. The assessment included demographic data, comorbidities, and postoperative complications after primary TKA for both DM and non-DM patients. The odds ratio (OR) was used to represent the estimate of risk of a specific outcome. Results: Thirty-nine studies were finally included in this meta-analysis. Patients with DM had higher rates of periprosthetic joint infection (OR: 1.71, 95% confidence interval [CI]: 1.46–2.00, p &lt; 0.01) and prosthesis revision (OR: 1.37, 95% CI: 1.23–1.52, p &lt; 0.01). Moreover, patients with DM showed an elevated incidence of pneumonia (OR: 1.54, 95% CI: 1.15–2.07, p &lt; 0.01), urinary tract infection (OR: 1.86, 95% CI: 1.07–3.26, p = 0.02), and sepsis (OR: 1.61, 95% CI: 1.46–1.78, p &lt; 0.01). Additionally, the postoperative risk of cardiovascular (OR: 2.49, 95% CI: 1.50–4.17, p &lt; 0.01) and cerebrovascular (OR: 2.38, 95% CI: 1.48–3.81, p &lt; 0.01) events was notably higher in patients with DM. The presence of DM increased the risk of deep vein thrombosis (OR: 1.58, 95% CI: 1.22–2.04, p &lt; 0.01), but did not lead to an increased risk of pulmonary embolism. Most importantly, DM was associated with a higher mortality rate within 30 days after TKA (OR: 1.27, 95% CI: 1.02–1.60, p = 0.03). Conclusions: Patients with DM exhibited a higher rate of postoperative complications after TKA, and DM was associated with a higher mortality rate within 30 days after TKA. It is crucial to educate patients about the perioperative risk and develop evidence-based guidelines to prevent complications after TKA.

Clinically applicable optimized periprosthetic joint infection diagnosis via AI based pathology

Periprosthetic joint infection (PJI) is a severe complication after joint replacement surgery that demands precise diagnosis for effective treatment. We enhanced PJI diagnostic accuracy through three steps: (1) developing a self-supervised PJI model with DINO v2 to create a large dataset; (2) comparing multiple intelligent models to identify the best one; and (3) using the optimal model for visual analysis to refine diagnostic practices. The self-supervised model generated 27,724 training samples and achieved a perfect AUC of 1, indicating flawless case differentiation. EfficientNet v2-S outperformed CAMEL2 at the image level, while CAMEL2 was superior at the patient level. By using the weakly supervised PJI model to adjust diagnostic criteria, we reduced the required high-power field diagnoses per slide from five to three. These findings demonstrate AI’s potential to improve the accuracy and standardization of PJI pathology and have significant implications for infectious disease diagnostics.

Feasibility of mNGS in joint replacement patients exhibiting elevated ESR and CRP levels without an underlying diagnosis

ObjectiveThe aim of this study is to investigate the viability of performing initial artificial joint replacement surgery in patients presenting with unexplained elevations in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels.MethodsA cohort of 22 patients, comprising 11 cases each for knee and hip joint replacements, who underwent initial artificial joint replacement surgery between November 2020 and January 2022, was recruited. All patients exhibited elevated levels of ESR and CRP prior to surgery, the etiology of which remained undetermined. Intraoperatively, joint effusion and periarticular tissues were preserved for subsequent bacterial culture and metagenomic next-generation sequencing (mNGS). Postoperatively, a combination of intravenous and local antibiotics was administered for anti-infective management. In cases where bacterial culture and/or mNGS yielded positive results, patients were diagnosed with periprosthetic joint infections (PJI) and underwent one-stage revision; conversely, negative findings led to the discontinuation of intravenous and local antibiotics therapy.ResultsAmong the cohort of 22 patients, bacterial cultures yielded negative results, while mNGS identified bacterial infection in 14 patients (63.63%), viral infection in 1 patient (4.55%), and yielded negative results in 7 patients (31.82%). All surgical incisions achieved per primam. Subsequent follow-up assessments conducted for more than 1 year postoperatively revealed absence of PJI among the patients, all of whom exhibited satisfactory progress in their rehabilitation exercises. Notably, the Knee Society Score (KSS) for knee joint patients significantly improved from a preoperative mean of 48.7 ± 3.3 points to 84.3 ± 2.2 points postoperatively, whereas the Harris Hip Score for hip joint patients increased significantly from preoperative mean of 50.6 ± 3.6 points to 87.1 ± 1.6 points (P < 0.01).ConclusionIn cases where patients present with unexplained elevations in ESR and CRP levels, primary artificial joint replacement can be undertaken following a one-stage revision approach for PJI.

The effect of prebiotic fibre on the gut microbiome and surgical outcomes in patients with prosthetic joint infection (PENGUIN) - study protocol for a randomised, double-blind, placebo-controlled trial (ACTRN12623001273673)

BackgroundProsthetic Joint Infection (PJI) is the most devastating complication of arthroplasty surgery and affects 1–5% of patients. Despite strict adherence to aseptic protocols and preventive measures, infection is the most common reason for revision arthroplasty, and the incidence is increasing. Treatment of PJI is challenging and often requires repeated major surgeries with sequentially poor results. The continued occurrence of PJI, and persistence after treatment, brings into question the current treatment paradigm. Preclinical evidence suggests a link between altered gut health and the risk of PJI in arthroplasty patients. Resistant starches helps to restore gut physiology by enhancing the beneficial microbiome and producing short-chain fatty acids, which have several health-conferring properties. The primary aim of this study is to investigate the effect of a commercially available prebiotic fibre formulation on the gut microbiome in PJI patients planned for a two-stage revision surgery.MethodsA double-blind placebo-controlled trial will assess the effect of 8-week supplementation of a commercially available prebiotic supplement in patients presenting with first-time PJI undergoing two-stage revision surgery. The supplementation phase will start after the first stage revision, and 80 patients will be randomised to receive either a test product (34 g of resistant starch) or a placebo (custard powder) daily for eight weeks. Stool and blood specimens will be collected at baseline, four weeks and eight weeks after the first-stage surgery and once at second-stage surgery. Gut microbiome profile, inflammatory cytokines and gut permeability biomarkers will be measured. Tissue specimens will be collected intra-operatively during first and second-stage surgeries. Baseline dietary patterns and gut symptoms will be recorded using validated questionnaires. Treatment outcomes will be reported for both cohorts using the Delphi criterion at one and two years after second-stage surgery.DiscussionThis will be the first study to investigate the relationship between gut health optimisation and preventing PJI recurrence in arthroplasty patients. If supplementation with resistant starch improves gut health and reduces systemic inflammation, optimising the gut microbiome will be a recommended preoperative management strategy for arthroplasty patients.Trial registration noACTRN12623001273673.

How Much Does Prosthetic Joint Infection and Its Successful Treatment Affect Patient-reported Quality of Life?

Uncomplicated joint replacement improves pain and other patient-reported outcome measures (PROMs) such as joint function scores and quality-of-life measures. However, the overall impact of periprosthetic joint infection (PJI) and its successful treatment on PROMs is poorly defined. In this study, we describe quality-of-life scores using the 12-item Short Form survey, version 2 (SF-12v2), collected as part of a large, prospective, observational study of PJI. (1) Do patients with newly diagnosed PJI have lower quality-of-life scores than the general age-matched population? (2) Are lower quality-of-life scores for patients with PJI sustained for ≥ 12 months? (3) What factors are associated with a good functional outcome at 12 months, defined by achieving a physical component summary (PCS) score of > 50 on the SF-12v2 (that is, above the age-adjusted population mean) or an increase of > 8.9 or more from baseline? The PIANO (Prosthetic joint Infection in Australia and New Zealand, Observational study) cohort was a prospective, longitudinal, multicenter cohort study of 783 patients with newly diagnosed PJI recruited across 27 centers between July 2014 and December 2017. All participants were followed for 2 years. SF-12v2 scores were collected at diagnosis (baseline) and 3, 12, and 24 months after diagnosis. Treatment success was defined as being alive with no clinical or microbiological evidence of infection and no ongoing use of antibiotics for the index joint. After exclusion of 6.6% (52) who had died, 4.2% (33) with PJI of joints other than hips and knees, and those with incomplete data sets (200 [25.5%]), 498 patients had complete SF-12v2 data sets available. At baseline, the median (IQR) PCS score was 37 (30 to 46), which increased to 41 (34 to 49; p < 0.001) at 12 months. Both measures were lower than those for the general age-matched population norm. There was no further improvement in PCS scores between 12 and 24 months. By contrast, the median (IQR) mental component summary score of the SF-12v2 was similar to age-adjusted population norms (48 [37 to 57]) at baseline. Only 40% of patients with PJI achieved a good functional outcome at 12 months. After adjustment for other factors, treatment success of PJI increased the odds of a good functional outcome by 67% (95% CI 11% to 154%; p = 0.02). PJIs have a large effect on the PCS score of the SF-12v2 quality-of-life measure at baseline, which is sustained for at least 2 years. Successful treatment of PJI increases the likelihood of a good functional outcome. These data can be used to set expectations for patients presenting with PJI and can be used to inform future clinical studies in which quality-of-life measures are incorporated into clinical endpoints. Level II, therapeutic study.

Imaging of Osteomyelitis

In this paper, an analysis of the demographic attributes, presenting symptoms, and infective agents, as well as the areas affected by skull osteomyelitis, of fifty male and fifty female patients is offered. A rough age estimate of around 61 years was found among the patients, with average symptom durations of about 6.8 months or longer. A significant percentage of diabetes (62%) and cranial nerve involvement (62%) were observed. The dominant symptom was headaches, representing 78% of cases, followed by cranial nerve palsy (62%) and hearing loss (48%). S. aureus was found to be the second most common causative agent, following only P. aeruginosa, which was the most common agent (54%). It became clear that there was a relevant infection in the temporomandibular joint and the retropharyngeal joint upon examining regional cases of the illness. In spite of therapy, only 38 percent of patients exhibited a cure, while 46 percent demonstrated improvement and 16 percent experienced a worsening of their condition.

The Use of a Novel Surgical Irrigant May Be Associated with Decreased Incidence of Surgical Site Infections

Background Periprosthetic joint infection (PJI) represents a formidable challenge to patients undergoing elective total hip arthroplasty (THA) and total knee arthroplasty (TKA). This investigation evaluated a novel antimicrobial surgical irrigation solution, XPerience (XP) (Next Science LLC, Jacksonville, FL), with proven high &amp; persistent in-vivo efficacy against planktonic bacteria and biofilm. The primary objective of this investigation was to compare the incidence of PJI following TKA performed with use of XP versus a standard control rinse (povidone-iodine). The secondary outcome was an all-cause return to operating room (OR) rate. Methods A retrospective cohort study was conducted from 824 consecutive patients undergoing primary THA/TKA from 12/1/2019 - 11/30/2021 treated using povidone-iodine solution and 471 consecutive patients undergoing primary THA/TKA from 12/1/2021 - 12/30/2022 treated with XP at a single institution by the senior author. All surgeries in both groups followed largely identical preoperative, perioperative, and postoperative protocols. A total of 1,295 cases were analyzed. The groups shared largely analogous background characteristics pertaining to age, sex, BMI, and American Society of Anesthesiologists (ASA) class. Results The overall SSI rate was 0% (0/471) in the XP group and 0.49% (4/824) in the control group (P = 0.3). The overall return to OR rate was 0.21% (1/471) in the XP group and 0.85% (7/824) in the control group (P = 0.3). Control group cases returned to the OR for hematoma debridements, periprosthetic fracture fixation, and PJI revisions. Conclusion This investigation is the first to remark on the clinical efficacy of a novel surgical irrigant. There was no statistically significant difference in rates of PJI or return to OR with the irrigant versus without, though a trend towards lower rates was observed in the context of a low baseline infection rate. Limitations pertaining to a single-center experience and sample size may be addressed by further studies incorporating broader enrollments.

Predicting periprosthetic joint infection: external validation of preoperative prediction models

Abstract. Introduction: Prediction models for periprosthetic joint infections (PJIs) are gaining interest due to their potential to improve clinical decision-making. However, their external validity across various settings remains uncertain. This study aimed to externally validate promising preoperative PJI prediction models in a recent multinational European cohort. Methods: Three preoperative PJI prediction models – by Tan et al. (2018), Del Toro et al. (2019), and Bülow et al. (2022) – that have previously demonstrated high levels of accuracy were selected for validation. A retrospective observational analysis of patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) at centers in the Netherlands, Portugal, and Spain between January 2020 and December 2021 was conducted. Patient characteristics were compared between our cohort and those used to develop the models. Performance was assessed through discrimination and calibration. Results: The study included 2684 patients, 60 of whom developed a PJI (2.2 %). Our cohort differed from the models' original cohorts with respect to demographic variables, procedural variables, and comorbidity prevalence. The overall accuracies of the models, measured with the c statistic, were 0.72, 0.69, and 0.72 for the Tan, Del Toro, and Bülow models, respectively. Calibration was reasonable, but the PJI risk estimates were most accurate for predicted infection risks below 3 %–4 %. The Tan model overestimated PJI risk above 4 %, whereas the Del Toro model underestimated PJI risk above 3 %. Conclusions: The Tan, Del Toro, and Bülow PJI prediction models were externally validated in this multinational cohort, demonstrating potential for clinical application in identifying high-risk patients and enhancing preoperative counseling and prevention strategies.

Risk of orthopaedic implant infection during bacteraemia.

Orthopaedic implant material can get infected via haematogenous spread from a distant source at any point after implantation. The sources of haematogenous orthopaedic implant infections have been studied only for prosthetic joints. The most common source of infection has varied, but it can be, for example from the skin and soft tissues, cardiovascular system and dental infections. The risk for developing a periprosthetic joint infection (PJI) during bacteraemia is dependent on the pathogen: it is highest for Staphylococcus aureus and beta-haemolytic streptococci, but low for gram-negative bacteria. The risk for developing a (PJI) during Staphylococcus aureus bacteraemia (SAB) has varied between 12 and 41%; the risk for developing an infection in any orthopaedic implant in the extremities during SAB is probably almost the same as for prosthetic joints, but data are very limited. The risk of developing an infection in spinal implants during bacteraemia is not known, as it has not been studied. Especially in the case of SAB, infected orthopaedic implants are usually symptomatic, so asymptomatic implants do not routinely require further diagnostic work-up, such as synovial fluid aspiration.

Joint Injection or Aspiration before Total Knee Arthroplasty: Does it Increase the Risk of Periprosthetic Joint Infection?

Background Injections are a common preoperative treatment for patients who eventually undergo total knee arthroplasty (TKA). However, recent studies have shown a relationship between preoperative injections and adverse outcomes following surgery. The purpose of this study was to characterize the type of intra-articular procedure patients receive in the acute period prior to surgery and determine their association with postoperative periprosthetic joint infection (PJI) Methods An observational cohort study was conducted using the Merative MarketScan databases. Patients who underwent primary TKA between April 1, 2019, and July 4, 2021, were included in the study. Patients were grouped according to the type of intra-articular procedure they received in the 90-day period prior to TKA: (i) intra-articular hyaluronic (IA-HA), (ii) intra-articular corticosteroid (IA-CS), (iii) aspiration, and (iv) no drug injections or aspirations. The primary outcome was the postoperative 180-day PJI rate. Results 43,219 patients were included in the study. 11.8% of patients were found to have received at least one injection or aspiration in the 90 days prior to their TKA. The most common injection performed was IA-CS (78.3%), followed by aspiration (13.0%) and IA-HA (8.7%). No image guidance was performed for 92.3% of injections, with most being administered between 61-90 days before surgery (93.6%). 180-day PJI rates were similar between patients with and without injections (OR 1.11, p=.569). Neither drug type nor image guidance had an effect on overall postoperative PJI rate. Conclusion Injections performed prior to TKA do not increase the risk of developing postoperative.

Application of a metatranscriptomics technology, CSI-Dx, for the detection of pathogens associated with prosthetic joint infections

Preoperative identification of causal organism(s) is crucial for effective prosthetic joint infection treatment. Herein, we explore the clinical application of a novel metatranscriptomic (MT) workflow, CSI-Dx, to detect pathogens associated with prosthetic joint infection. MT provides insight into transcriptionally active microbes, overcoming limitations of culture-based and available molecular methods. This study included 340 human synovial fluid specimens subjected to CSI-Dx and traditional culture-based methods. Exploratory analyses were conducted to determine sensitivity and specificity of CSI-Dx for detecting clinically-relevant taxa. Our findings provide insights into the active microbial community composition of synovial fluid from arthroplasty patients and demonstrate the potential clinical utility of CSI-Dx for aiding prosthetic joint infection diagnosis. This approach offers potential for improved sensitivity and acceptable specificity compared to synovial fluid culture, enabling detection of culturable and non-culturable microorganisms. Furthermore, CSI-Dx provides valuable information on antimicrobial resistance gene expression. While further optimization is needed, integrating metatranscriptomic technologies like CSI-Dx into routine clinical practice can revolutionize prosthetic joint infection diagnosis by offering a comprehensive and active snapshot of associated pathogens.

Bone allograft impregnated with tobramycin and vancomycin delivers antibiotics in high concentrations for prophylaxis against bacteria commonly associated with prosthetic joint infections.

Local delivery of antibiotics as prophylaxis for prosthetic joint infections (PJIs) is frequently used during total hip replacement surgery. Morselized bone allograft impregnated with vancomycin and tobramycin (TobraVanc) could provide effective prophylaxis against bacteria commonly associated with PJIs. In this study, the concentrations of antibiotics released by bone allograft impregnated with TobraVanc were determined by using an in vitro bioassay system entailing measuring inhibition zone diameters caused by antibiotic-impregnated bone chips cast in agar against standard curves. The concentrations were determined in samples of TobraVanc-impregnated bone graft taken before and after the application of the bone graft in the patients undergoing acetabular revision surgery. Antibiotic-impregnated bone grafts, sampled prior to application in the patient, delivered antibiotics in the concentration ranges of 730-9,800 mg/L for tobramycin and 1,300-11,000 mg/L for vancomycin. Samples taken after application in the patient released lower concentrations of tobramycin (490-1,900 mg/L; P < 0.01) and vancomycin (3,000-5,100 mg/L; P < 0.05); however, these concentrations remained well above the tobramycin minimum inhibitory concentrations (MICs) for investigated, highly tobramycin-resistant Staphylococcus epidermidis strains (MICs > 256 mg/L). At the tested concentrations, bone graft material mixed with TobraVanc delivered antibiotics in potent concentrations above the MICs for bacteria causing PJIs. Clinical trials are needed to evaluate the efficacy and risk of TobraVanc-impregnated bone graft as a prophylactic agent for patients undergoing hip replacement surgery.IMPORTANCEAntibiotic prophylaxis is the cornerstone of successful joint replacement surgery, reducing the risk for the dreaded complication of prosthetic joint infection (PJI) to roughly 0.5%-2% in standard total hip replacement (THR). In addition to systemic antibiotics, antibiotics added locally have the potential to reduce the PJI risk even further, because of the high concentrations that can be achieved in the joint with limited risk for systemic toxicity. The results in the current study show that bone chips impregnated with a combination of tobramycin and vancomycin (TobraVanc) release antibiotics in concentrations that are potent against common bacteria causing PJIs. Especially in high-risk patients, our results support the prophylactic use of TobraVanc in hip replacement surgery requiring the use of a bone graft. A clinical study testing the efficacy of TobraVanc-impregnated bone graft in reducing the incidence of PJI in hip replacement surgery is currently ongoing (EudraCT: 2021-001708-14).

Never Assume Successful Treatment of Septic Arthritis: Bacteria Isolated at Revision ACL Reconstruction 3 Years After Primary ACL Reconstruction "Successfully" Treated for Infection.

Level IV.

Effect of non-contact induction heating on HA coatings and bone cement, an ex vivo study

Background Prosthetic joint infection is a serious complication that can arise after total joint replacement surgery. When bacteria colonise an orthopaedic implant, they form biofilms that protect them from their environment, making them difficult to remove. Treatment is further complicated by a global rise of antimicrobial resistance. These protective mechanisms make treatment of prosthetic joint infection increasingly complex. Non-contact induction heating is an upcoming technology that uses heat to eradicate bacteria that are present on the surface of metallic implants. This study aims to provide insight into the feasibility of using non-contact induction heating on metallic implants that are in direct contact with other biomaterials, such as coatings composed of hydroxyapatite and bone cement composed of poly (methyl methacrylate) (PMMA). Methods Characterisation of hydroxyapatite coatings and adhesion strength tests were conducted according to standards set by the International Organisation for Standardisation (ISO 13779-2). The fixation strength of acrylic bone cement was tested according to an adapted method from ISO. Results It was found that non-contact induction heating did not significantly affect the adhesion strength of hydroxyapatite coatings. In contrast to hydroxyapatite coatings, acrylic bone cement softened temporarily as the temperature exceeded the glass transition temperature (83.38 ± 10.88°C). However, the induction heating temperature had no significant effect on the fixation strength after the cement was allowed to cool down. Conclusion This study shows the feasibility of using non-contact induction heating up to 80°C when bone cement or ceramic coatings are present in contact with infected metallic implants.

Preclinical Positron Emission Tomography (PET) of Prosthetic Joint Infection Using a Nitro-Prodrug of 2-[18F]F-p-Aminobenzoic Acid ([18F]F-PABA).

Deep-seated bacterial infections are difficult to detect and diagnose due to the lack of specific clinical imaging modalities. Therefore, the bacteria-specific positron emission tomography radiotracer 2-[18F]fluoro-4-nitrobenzoic acid ([18F]FNB) was developed, which is reduced to 2-[18F]fluoro-4-aminobenzoic acid ([18F]F-PABA) by bacterial nitroreductases and has improved pharmacokinetics compared to the parent compound. PET imaging demonstrated that the uptake of 2-[18F]fluoro-4-nitrobenzoic acid in a clinically relevant Staphylococcus aureus prosthetic joint infection model was up to ∼4-fold higher in the infected joint compared to the contralateral joint. 2-[18F]Fluoro-4-nitrobenzoic acid was also able to distinguish infection from inflammation in a surgical inflammation model. Based on the mouse radiation dosimetry results, the calculated effective dose of 2-[18F]fluoro-4-nitrobenzoic acid was well below the whole-body radiation dose limit established by the Food and Drug Administration for humans. In addition, no treatment-related microscopic changes in organ histopathology were observed in a mouse acute toxicity study. Overall, these data suggest that 2-[18F]fluoro-4-nitrobenzoic acid is a specific and effective imaging agent for noninvasively diagnosing prosthetic joint infections.