Aims. There is little information regarding the risk of a patient developing prosthetic joint infection (PJI) after primary total knee arthroplasty (TKA) when the patient has previously experienced PJI of a TKA or total hip arthroplasty (THA) in another joint. The goal of this study was to compare the risk of PJI of primary TKA in this patient population against matched controls. Patients and Methods. We retrospectively reviewed 95 patients (102 primary TKAs) treated between 2000 and 2014 with a history of PJI in another TKA or THA. A total of 50 patients (53%) were female. Mean age was 69 years (45 to 88) with a mean body mass index (BMI) of 36 kg/m. 2. (22 to 59). In total, 27% of patients were on chronic antibiotic suppression. Mean follow-up was six years (2 to 16). We 1:3 matched these (for age, sex, BMI, and surgical year) to 306 primary TKAs performed in 306 patients with a THA or TKA of another joint without a subsequent PJI. Competing risk with death was used for statistical analysis. Multivariate analysis was followed to evaluate risk factors for PJI in the study cohort. Results. The cumulative incidence of PJI in the study cohort (6.1%) was significantly higher than the matched cohort (2.6%) at ten years (hazard ratio (HR) 3.3; 95% confidence interval 1.18 to 8.97; p = 0.02). Host grade in the study group was not a significant risk factor for PJI. Patients on chronic suppression had a higher rate of PJI (HR 15; p = 0.002), with six of the seven patients developing PJI in the study group being on chronic suppression. The new infecting microorganism was the same as the previous in only two of seven patients. Conclusion. In this matched cohort study, patients undergoing a clean primary TKA with a history of TKA or THA PJI in another joint had a three-fold higher risk of PJI compared with matched controls with ten-year cumulative incidence of 6.1%. The risk of PJI was 15-fold higher in patients on chronic antibiotic suppression; further investigation into reasons for this and mitigation strategies are recommended. Cite this article: Bone Joint J 2019;101-B(7 Supple C):91–97

Aim. Prosthetic joint replacement is more commonly done in the elderly group of patients due to an increase pathology related to joint degeneration that comes with age. In this age group is also more frequent having underling condition that may predispose to a prosthetic joint infection. Also, the pharmacological intervention in those patients may play an important role as a risk factor for infection after joint replacement surgery. The use of oral anticoagulants seems to be particularly increased in elderly patients but there aren't enough data published to support an association between prosthetic joint infection and the use of oral anticoagulants. Identifying risk factors in elderly patients age >75 years old with a special focus on the oral anticoagulation therapy is the aim of the study. Methods. In a retrospective study from 2011 till 2018 all the patients >75 years old with knee and hip replacement surgery have been review looking for acute prosthetic infection and risk factors that may be predispose to it. Patients with previous surgery or any other mechanical complication that needed intervention on the same area have been excluded. Results. A total of 1220 patients have been included (801 knee replacement surgery and 419 hip replacement surgery). The mean age was 79.5 ± 3.44 years and most of the patients were women (72,6%). The infection rate was 2,5%. Several factors have been identified to be associated with acute infection. (Table.1.). The patients receiving oral anticoagulants had an increased risk of infection (OR 3.63 (1.60–7.74), p=0.002). Conclusions. Even all the risk factors associated with risk infection have been described previously, the relevant aspect is the increased risk of prosthetic joint infection in patients receiving oral anticoagulants

Aims. Periprosthetic hip-joint infection is a multifaceted and highly detrimental outcome for patients and clinicians. The incidence of prosthetic joint infection reported within two years of primary hip arthroplasty ranges from 0.8% to 2.1%. Costs of treatment are over five-times greater in people with periprosthetic hip joint infection than in those with no infection. Currently, there are no national evidence-based guidelines for treatment and management of this condition to guide clinical practice or to inform clinical study design. The aim of this study is to develop guidelines based on evidence from the six-year INFection and ORthopaedic Management (INFORM) research programme. Methods. We used a consensus process consisting of an evidence review to generate items for the guidelines and online consensus questionnaire and virtual face-to-face consensus meeting to draft the guidelines. Results. The consensus panel comprised 21 clinical experts in orthopaedics, primary care, rehabilitation, and healthcare commissioning. The final output from the consensus process was a 14-item guideline. The guidelines make recommendations regarding increased vigilance and monitoring of those at increased risk of infection; diagnosis including strategies to ensure the early recognition of prosthetic infection and referral to orthopaedic teams; treatment, including early use of DAIR and revision strategies; and postoperative management including appropriate physical and psychological support and antibiotic strategies. Conclusion. We believe the implementation of the INFORM guidelines will inform treatment protocols and clinical pathways to improve the treatment and management of periprosthetic hip infection. Cite this article: Bone Jt Open 2023;4(4):226–233

Objectives. We used the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man (NJR) to investigate the risk of revision due to prosthetic joint infection (PJI) for patients undergoing primary and revision hip arthroplasty, the changes in risk over time, and the overall burden created by PJI. Methods. We analysed revision total hip arthroplasties (THAs) performed due to a diagnosis of PJI and the linked index procedures recorded in the NJR between 2003 and 2014. The cohort analysed consisted of 623 253 index primary hip arthroplasties, 63 222 index revision hip arthroplasties and 7585 revision THAs performed due to a diagnosis of PJI. The prevalence, cumulative incidence functions and the burden of PJI (total procedures) were calculated. Overall linear trends were investigated with log-linear regression. Results. We demonstrated a prevalence of revision THA due to prosthetic joint infection of 0.4/100 procedures following primary and 1.6/100 procedures following revision hip arthroplasty. The prevalence of revision due to PJI in the three months following primary hip arthroplasty has risen 2.3-fold (95% confidence interval (CI) 1.3 to 4.1) between 2005 and 2013, and 3.0-fold (95% CI 1.1 to 8.5) following revision hip arthroplasty. Over 1000 procedures are performed annually as a consequence of hip PJI, an increase of 2.6-fold between 2005 and 2013. Conclusions. Although the risk of revision due to PJI following hip arthroplasty is low, it is rising and, coupled with the established and further predicted increased incidence of both primary and revision hip arthroplasty, this represents a growing and substantial treatment burden. Cite this article: E. Lenguerrand, M. R. Whitehouse, A. D. Beswick, S. A. Jones, M. L. Porter, A. W. Blom. Revision for prosthetic joint infection following hip arthroplasty: Evidence from the National Joint Registry. Bone Joint Res 2017;6:391–398. DOI: 10.1302/2046-3758.66.BJR-2017-0003.R1

Aim. Culture negative (CN) prosthetic joint infections (PJI) account for approximately 10% of all PJIs and present significant challenges for clinicians. We aimed to explore the significance of CN PJI within a large prospective cohort study, and to compare their characteristics and outcomes with culture positive cases. Methods. The Prosthetic joint Infection in Australia and New Zealand Observational (PIANO) study is a prospective, binational, multicentre observational cohort study conducted at 27 hospitals between July 2014 and December 2017. We compared baseline characteristics and outcomes of all patients with culture negative (CN) prosthetic joint infection (PJI) from the PIANO cohort with culture positive (CP) cases. “Treatment success” was defined as absence of clinical or microbiological signs of infection, no need for ongoing antibiotics, and no need for revision or resection arthroplasty since the end of the initial treatment. We also describe PJI diagnostic criteria in the CN cohort and apply internationally recognised PJI diagnostic guidelines. Results. Of the 650 patients eligible for inclusion, 55 (8.5%) were CN and 595 were CP. Compared with the CP cohort, CN patients were more likely to be female [32 (58.2%) vs 245 (41.2%); p=0.02], involve the shoulder joint [5 (9.1%) vs. 16 (2.7%); p=0.03] and have a lower mean C-reactive protein (142 mg/L vs. 187 mg/L; p=0.02). Overall, outcomes were superior in CN patients, with culture negativity an independent predictor of treatment success at 24 months (aOR 3.78; 95%CI 1.65 – 8.67). Of the 55 CN cases meeting Infectious Diseases Society of America (IDSA) diagnostic criteria, 45 (82%) met European Bone and Joint Infection Society (EBJIS) criteria (probable or definite) and 39 (71%) met the 2013 Musculoskeletal Infection Society (MSIS) criteria. Conclusions. Culture negativity is an independent predictor of treatment success in PJI. It is unclear whether this is because some of them are not actually infections, or for other reasons such as lower bacterial load or earlier effective antibiotic treatment. Diagnostic criteria for PJI vary substantially in their sensitivity, with MSIS criteria being the least sensitive. Acknowledgements. This work is being presented on behalf of the broader PIANO investigators and the Australasian Society for Infectious Diseases Clinical Research Network. The PIANO study received seed funding from Heraeus Medical and the John Hunter Hospital Charitable Trust Fund

Aims. Two-stage exchange arthroplasty is the most common definitive treatment for prosthetic joint infection (PJI) in the USA. Complications that occur during treatment are often not considered. The purpose of this study was to analyze complications in patients undergoing two-stage exchange for infected total knee arthroplasty (TKA) and determine when they occur. Methods. We analyzed all patients that underwent two-stage exchange arthroplasty for treatment of PJI of the knee from January 2010 to December 2018 at a single institution. We categorized complications as medical versus surgical. The intervals for complications were divided into: interstage; early post-reimplantation (three months); and late post-reimplantation (three months to minimum one year). Minimum follow-up was one year. In total, 134 patients underwent a first stage of a two-stage exchange. There were 69 males and 65 females with an mean age at first stage surgery of 67 years (37 to 89). Success was based on the new Musculoskeletal Infection Society (MSIS) definition of success reporting. Results. Overall, 70 (52%) patients experienced a complication during the planned two-stage treatment, 36 patients (27%) experienced a medical complication and 47 (41%) patients experienced a surgical complication. There was an 18% mortality rate (24/134) at a mean of 3.7 years (0.09 to 8.3). During the inter-stage period, 28% (37/134) of patients experienced a total of 50 complications at a median of 47 days (interquartile range (IQR) 18 to 139). Of these 50 complications, 22 were medical and 28 required surgery. During this inter-stage period, four patients died (3%) and an additional five patients (4%) failed to progress to the second stage. While 93% of patients (125/134) were reimplanted, only 56% (77/134) of the patients were successfully treated without antibiotic suppression (36%, 28/77) or with antibiotic suppression (19%, 15/77) at one year. Conclusion. Reported rates of success of two stage exchanges for PJI have not traditionally considered complications in the definition of success. In our series, significant numbers of patients experienced complications, more often after reimplantation, highlighting the morbidity of this method of treatment. Cite this article: Bone Joint J 2020;102-B(6 Supple A):145–150

Objectives. Prosthetic joint infection (PJI) diagnosis is a major challenge in orthopaedics, and no reliable parameters have been established for accurate, preoperative predictions in the differential diagnosis of aseptic loosening or PJI. This study surveyed factors in synovial fluid (SF) for improving PJI diagnosis. Methods. We enrolled 48 patients (including 39 PJI and nine aseptic loosening cases) who required knee/hip revision surgery between January 2016 and December 2017. The PJI diagnosis was established according to the Musculoskeletal Infection Society (MSIS) criteria. SF was used to survey factors by protein array and enzyme-linked immunosorbent assay to compare protein expression patterns in SF among three groups (aseptic loosening and first- and second-stage surgery). We compared routine clinical test data, such as C-reactive protein level and leucocyte number, with potential biomarker data to assess the diagnostic ability for PJI within the same patient groups. Results. Cut-off values of 1473 pg/ml, 359 pg/ml, and 8.45 pg/ml were established for interleukin (IL)-16, IL-18, and cysteine-rich with EGF-like domains 2 (CRELD2), respectively. Receiver operating characteristic curve analysis showed that these factors exhibited an accuracy of 1 as predictors of PJI. These factors represent potential biomarkers for decisions associated with prosthesis reimplantation based on their ability to return to baseline values following the completion of debridement. Conclusion. IL-16, IL-18, and CRELD2 were found to be potential biomarkers for PJI diagnosis, with SF tests outperforming blood tests in accuracy. These factors could be useful for assessing successful debridement based on their ability to return to baseline values following the completion of debridement. Cite this article: M-F. Chen, C-H. Chang, L-Y. Yang, P-H. Hsieh, H-N. Shih, S. W. N. Ueng, Y. Chang. Synovial fluid interleukin-16, interleukin-18, and CRELD2 as novel biomarkers of prosthetic joint infections. Bone Joint Res 2019;8:179–188. DOI: 10.1302/2046-3758.84.BJR-2018-0291.R1

Prosthetic joint infections (PJI) are devastating complications. Our knowledge on hip fractureassociated hemiarthroplasty PJI (HHA-PJI) is limited compared to elective arthroplasty. The goal of this study was to describe the epidemiology, risk factors, management, and outcomes for HHA-PJI. A population-based (465,000) multicentre retrospective analysis of HHAs between 2006-2018 was conducted. PJI was defined by international consensus and treatment success as no return to theatre and survival to 90 days after the initial surgical management of the infection. Univariate, survival and competing risk regression analyses were performed. 1852 HHAs were identified (74% female; age:84±7yrs;90-day-mortality:16.7%). Forty-three (2.3%) patients developed PJI [77±10yrs; 56% female; 90-day-mortality: 20.9%, Hazard-Ratio 1.6 95%CI 1.1-2.3,p=0.023]. The incidence of HHA-PJI was 0.77/100,000/year and 193/100,000/year for HHA. The median time to PJI was 26 (IQR 20-97) days with 53% polymicrobial growth and 41% multi-drug resistant organisms (MDRO). Competing risk regression identified younger age [Sub-Hazard-Ratio(SHR) 0.86, 95%CI 0.8-0.92,p<0.001], chronic kidney disease (SHR 3.41 95%CI 1.36-8.56, p=0.01), body mass index>35 (SHR 6.81, 95%CI 2.25-20.65, p<0.001), urinary tract infection (SHR 1.89, 95%CI 1.02-3.5, p=0.04) and dementia (SHR 9.4, 95%CI 2.89-30.58,p<0.001) as significant risk factors for developing HHA-PJI. When infection treatment was successful (n=15, 38%), median survival was 1632 days (IQR 829-2084), as opposed to 215 days (IQR 20-1245) in those who failed, with a 90-day mortality of 30%(n=12). There was no significant difference in success among debridement, excision arthroplasty or revision arthroplasty. HHA PJI is uncommon but highly lethal. All currently identified predictors are non-modifiable. Due to the common polymicrobial and MDRO infections our standard antibiotic prophylaxis may not be adequate HHA-PJI is a different disease compared to elective PJI with distinct epidemiology, pathogens, risk factors and outcomes, which require targeted research specific to this unique population

Introduction. A proportion of patients with hip and knee prosthetic joint infection (PJI) undergo multiple revisions with the aim of eradicating infection and improving quality of life. The aim of this study was to describe the microbiology cultured from multiply revised hip and knee replacement procedures to guide antimicrobial therapy at the time of surgery. Patients and Methods. Consecutive patients were retrospectively identified from databases at two specialist orthopaedic centres in the United Kingdom between 2011 and 2019. Patient were included who had undergone repeat revision total knee replacement (TKR) or total hip replacement (THR) for infection, following an initial failed revision for infection. Results. 106 patients were identified, of which 74 underwent revision TKR and 32 underwent revision THR. Mean age at first revision was 67 years (SD 10). Charlson Comorbidity Index was <2 for 31 patients, 3–4 for 57 patients, and >5 for 18 patients. All patients underwent >2 revisions, 73 patients received 3, 47 patients received 4, 31 patients received 5, and 21 patients received >6. After six revisions, 90% of patients cultured different organisms than the initial revision, and 53% of organisms were multi-drug resistant species. The most frequent organisms at each revision were coagulase negative Staphylococcus (36%) and Staphylococcus aureus (19%). Fungus was cultured from 3% of revisions and 21% of infections were polymicrobial. Conclusion. Patients undergoing multiple revisions for PJI are highly likely to experience a change in organisms and sensitivities with each subsequent revision. It is important to administer empirical antibiotics at each subsequent revision, appreciating known drug resistance from previous cultures. Our results do not support routine use of empirical antifungals

Aims. This study aimed to evaluate calprotectin in synovial fluid for diagnosing chronic prosthetic joint infection (PJI) . Methods. A total of 63 patients who were suspected of PJI were enrolled. The synovial fluid calprotectin was tested by an enzyme-linked immunosorbent assay (ELISA). Laboratory test data, such as ESR, CRP, synovial fluid white blood cells (SF-WBCs), and synovial fluid polymorphonuclear cells (SF-PMNs), were documented. Chi-squared tests were used to compare the sensitivity and specificity of calprotectin and laboratory tests. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was calculated to determine diagnostic efficacy. Results. The median calprotectin level was 776 μg/ml (interquartile range (IQR) 536.5 to 1132) in the PJI group and 54.5 μg/ml (IQR, 38.75 to 78.25) in the aseptic failure (AF) group (p < 0.05). Using a threshold of 173 ug/ml, the sensitivity was 95.2%, with a 97.6% specificity, and the AUC was 0.993. The sensitivity of calprotectin of the antibiotic-treated PJI group was 100% versus 90.9% of the non-antibiotic-treated PJI group. Although 47.6% (ten cases) of the patients in the PJI group received antibiotics before aspiration, the diagnostic efficacy of calprotectin was not affected. The sensitivity and specificity of ESR, CRP, SF-WBCs, and SF-PMNs ranged from 76.2% to 90.5% and 64.3% to 85.7%, respectively. Conclusion. Calprotectin in synovial fluid has great diagnostic efficacy for PJI diagnosisand outperformed ESR, CRP, SF-WBCs, and SF-PMNs. Cite this article: Bone Joint Res 2020;9(8):450–456

Prosthetic joint infections (PJI) are one of the most devastating complications of joint replacement surgery. They are associated with significant patient morbidity and carry a significant economic cost to treat. The management of PJI varies from antibiotic suppression, debridement, antibiotics, and implant retention (DAIR) procedures through to single/multiple stage revision procedures. Concerns have been raised recently in relation to the rising number of revision arthroplasty procedures that are being undertaken in relation to infection. This database aims to collect data on all PJIs that have been managed in the Australian Capital Territory (ACT) region. This will allow us to investigate the microbial trends, outcomes of surgical intervention and patient outcomes within our local population. This database will incorporate diagnostic, demographic, microbiological and treatment information in relation to local PJI cases. The data will be collated from the local infectious diseases database, hospital medical records, and where available the Australian Orthopaedic Association National Joint Replacement Registry Data. The first 100 cases of PJI were assessed. 76% were defined as being acute. 56% of the patients received antibiotics prior to their diagnosis however only 3% were culture negative. 89% were monomicrobial and 11% polymicrobial. The intended management strategy was a DAIR in 38% of patients and a 2-stage revision in 12% of cases. The intended management strategy was successful in 46% of the patients. The ACT is uniquely placed to analyze and create a local PJI database. This will allow us to guide further treatment and local guidelines in terms of management of these complex patients

Objectives. Prosthetic joint infection (PJI) is the most common cause of arthroplasty failure. However, infection is often difficult to detect by conventional bacterial cultures, for which false-negative rates are 23% to 35%. In contrast, 16S rRNA metagenomics has been shown to quantitatively detect unculturable, unsuspected, and unviable pathogens. In this study, we investigated the use of 16S rRNA metagenomics for detection of bacterial pathogens in synovial fluid (SF) from patients with hip or knee PJI. Methods. We analyzed the bacterial composition of 22 SF samples collected from 11 patients with PJIs (first- and second-stage surgery). The V3 and V4 region of bacteria was assessed by comparing the taxonomic distribution of the 16S rDNA amplicons with microbiome sequencing analysis. We also compared the results of bacterial detection from different methods including 16S metagenomics, traditional cultures, and targeted Sanger sequencing. Results. Polymicrobial infections were not only detected, but also characterized at different timepoints corresponding to first- and second-stage exchange arthroplasty. Similar taxonomic distributions were obtained by matching sequence data against SILVA, Greengenes, and The National Center for Biotechnology Information (NCBI). All bacteria isolated from the traditional culture could be further identified by 16S metagenomics and targeted Sanger sequencing. Conclusion. The data highlight 16S rRNA metagenomics as a suitable and promising method to detect and identify infecting bacteria, most of which may be uncultivable. Importantly, the method dramatically reduces turnaround time to two days rather than approximately one week for conventional cultures. Cite this article: M-F. Chen, C-H. Chang, C. Chiang-Ni, P-H. Hsieh, H-N. Shih, S. W. N. Ueng, Y. Chang. Rapid analysis of bacterial composition in prosthetic joint infection by 16S rRNA metagenomic sequencing. Bone Joint Res 2019;8:367–377. DOI: 10.1302/2046-3758.88.BJR-2019-0003.R2

Aim. Prosthetic joint infection (PJI) is a devastating complication of joint replacement, having an impact on morbimortality but also on national health systems and their budgets. The current situation of PJI-related hospitalizations in Spain and their changes over time are unknown. Therefore, we aimed to analyze the hospitalization burden of PJI, including costs and trends in recent decades. Methods. Retrospective observational study including data from the National Surveillance System for Hospital Data, which includes more than 98% of Spanish hospitals. During the period 2000–2015, hospitalizations due to PJI (ICD-9-CM 996.66) as main diagnosis were included. Epidemiological trends were evaluated during four periods: P1, 2000–2003; P2, 2004–2007; P3, 2008–2011; P4, 2012–2015. Annual hospitalization rates per 100,000 inhabitants and trends were also calculated. Results. Among 5,721,6725 hospitalizations, 49,835 were PJI related, which represented 8.71/10,000 admissions. We observed a significant increase in the number of PJI-related hospitalizations per 10,000 admissions during the study period: 6.43 P1, 8.53 P2, 9.60 P3, 10.05 P4 (p<0.001). The annual hospitalization rate was 6.9/100,000 inhabitants (95%CI 6.9–7), which also increased over time (p<0.001). The median age was 72 years (IQR 65–78) and 58.12% were women. Hospitalization rates were higher in women (7.95 vs 5.90; p<0.001) and also increased with patients’ age (p<0.001). Whereas the median length of stay was 7 days (IQR 7–8) in the global cohort, it was 18 days (IQR 10–31) in those with PJI-related hospitalization; however, the median length of stay in PJI-related hospitalizations decreased during the study period (P1 20 days, P4 16 days, p<0.001). The total cost for the healthcare system was 366 million euros and the median cost per patient was 6937 euros (IQR 3584–10505), which significantly increased from 4804 euros in P1 to 8534 in P4 (p<0.001). The majority of patients (90.32%) were discharged home and the case-fatality rate was 2.70%, without significant differences during the study (p=0.384). Conclusions. In Spain, PJI-related hospitalizations have increased in recent decades, with higher costs despite the decrease in length of stay. PJI is a first magnitude healthcare problem, which should be prioritized in health systems and budgets

Gram-negative prosthetic joint infections (GN-PJI) present unique challenges in management due to their distinct pathogenesis of biofilm formation on implant surfaces. To date, there are no animal models that can fully recapitulate how a biofilm is challenged in vivo in the setting of GN-PJI. The purpose of this study is to establish a clinically representative GN-PJI in vivo model that can reliably depict biofilm formation on titanium implant surface. We hypothesized that the biofilm formation on the implant surface would affect the ability of the implant to be osseointegrated. The model was developed using a 3D-printed, medical-grade titanium (Ti-6Al-4V), monoblock, cementless hemiarthroplasty hip implant. This implant was used to replace the femoral head of a Sprague-Dawley rat using a posterior surgical approach. To induce PJI, two bioluminescent Pseudomonas aeruginosa (PA) strains were utilized: a reference strain (PA14-lux) and a mutant strain that is defective in biofilm formation (DflgK-lux). PJI development and biofilm formation was quantitatively assessed in vivo using the in vivo imaging system (IVIS), and in vitro using the viable colony count of the bacterial load on implant surface. Magnetic Resonance Imaging (MRI) was acquired to assess the involvement of periprosthetic tissue in vivo, and the field emission scanning electron microscopy (FE-SEM) of the explanted implants was used to visualize the biofilm formation at the bone-implant interface. The implant stability, as an outcome, was directly assessed by quantifying the osseointegration using microCT scans of the extracted femurs with retained implants in vitro, and indirectly assessed by identifying the gait pattern changes using DigiGaitTM system in vivo. A localized prosthetic infection was reliably established within the hip joint and was followed by IVIS in real-time. There was a quantitative and qualitative difference in the bacterial load and biofilm formation between PA14 and DflgK. This difference in the ability to persist in the model between the two strains was reflected on the gait pattern and implant osseointegration. We developed a novel uncemented hip hemiarthroplasty GN-PJI rat model. This model is clinically representative since animals can bear weight on the implant. PJI was detected by various modalities. In addition, biofilm formation correlated with implant function and stability. In conclusion, the proposed in vivo GN-PJI model will allow for more reliable testing of novel biofilm-targeting therapetics

Introduction. Gram-negative prosthetic joint infections (GN-PJI) present unique challenges in management due to their distinct pathogenesis of biofilm formation on implant surfaces. The purpose of this study is to establish a clinically representative GN-PJI model that can reliably recapitulate biofilm formation on titanium implant surface in vivo. We hypothesized that biofilm formation on an implant surface will affect its ability to osseointegrate. Methods. The model was developed using 3D-printed titanium hip implants, to replace the femoral head of male Sprague-Dawley rats. GN-PJI was induced using two bioluminescent Pseudomonas aeruginosa strains: a reference strain (PA14-lux) and a mutant biofilm-defective strain (ΔflgK-lux). Infection was monitored in real-time using the in vivo imaging system (IVIS) and Magnetic Resonance Imaging (MRI). Bacterial loads on implant surface and in periprosthetic tissues were quantified utilizing viable-colony-count. Field-emission scanning-electron-microscopy of the explanted implants was used to visualize the biofilm formation at the bone-implant-interface. The implant stability, as an outcome, was directly assessed by quantifying the osseointegration in vitro using microCT scan, and indirectly assessed by identifying the gait pattern changes using DigiGait. TM. system in vivo. Results. Localized infection was established within the hip joint and was followed by IVIS in real-time. There was a quantitative and qualitative difference in the bacterial load and biofilm formation between PA14-lux and ΔflgK-lux. This difference in the ability to persist in the model between the two strains was reflected in the gait pattern and implant osseointegration. Conclusions. We developed a novel uncemented hip hemiarthroplasty, GN-PJI rat model. To date, the proposed in vivo biofilm-based model is the most clinically representative for GN-PJI since animals can bear weight on the implant and poor osseointegration correlates with biofilm formation. In addition, localized PJI was detected by various modalities. Clinical Relevance. The proposed in vivo GN-PJI model will allow for more reliable testing of novel biofilm-targeting therapeutics

Aims. To investigate the experience and emotional impact of prosthetic joint infection (PJI) on orthopaedic surgeons and identify holistic strategies to improve the management of PJI and protect surgeons’ wellbeing. Methods. In total, 18 prosthetic joint surgeons in Sweden were recruited using a purposive sampling strategy. Content analysis was performed on transcripts of individual in-person interviews conducted between December 2017 and February 2018. Results. PJI had a negative emotional impact on Swedish surgeons. Many felt guilt, stress, and a sense of failure, and several aspects of PJI management were associated with psychosocial challenges. Peer support was reported as the most important coping strategy as was collaborating with infectious disease specialists. Conclusion. Our study affirms that there is a negative emotional impact of PJI on surgeons which can be minimized by improved peer support and working in multidisciplinary teams. Based on the surgeons’ experiences we have identified desired improvements that may facilitate the management of PJI. These may also be applicable within other surgical specialties dealing with postoperative infections, but need to be evaluated for their efficacy. Cite this article: Bone Joint J 2020;102-B(6):736–743

Aim. Prosthetic joint infection (PJI) is a serious complication following total hip arthroplasty (THA) entailing increased mortality, decreased quality of life, and high healthcare costs. In 2009 a nationwide, multidisciplinary infection control program was launched in Sweden, PRISS, which aimed to reduce the PJI burden by 50%. The primary aim was to investigate whether the PRISS project reduced PJI incidence after primary THA; the secondary aim was to evaluate other possible benefits of PRISS, such as shorter time to diagnosis. Method. We obtained data on patients undergoing primary THA in Sweden (n = 45,723 patients, 49,946 THAs), 2012–2014. Using personal identity numbers, this cohort was matched with the Swedish Prescribed Drug Registry. Medical records of patients with ≥4 weeks antibiotic consumption were reviewed to verify PJI diagnosis (n = 2240, 2569 THAs). Results. The cumulative incidence of PJI following the PRISS project was 1.2% [95% CI 1.1–1.3] as compared to 0.9% [95% CI 0.8–1.0] before. Cox regression models for the PJI incidence post PRISS indicates there were no statistical significance difference versus pre PRISS (HR 1.1 [95% CI 0.9–1.3]. There were similar time to PJI diagnosis after the PRISS project 24 vs 23 days (p=0.5). Conclusions. Despite the comprehensive nationwide PRISS project, Swedish PJI incidence was higher after the project and time to diagnosis remained unchanged. Factors contributing to PJI, such as increasing obesity, higher ASA class, and more fractures as indications, explain the PJI increase among primary THA patients

Aims. Fungal prosthetic joint infections (PJIs) are rare and account for about 1% of total PJIs. Our aim was to present clinical and microbiological results in treating these patients with a two-stage approach and antifungal spacers. Patients and Methods. We retrospectively reviewed our institutional database and identified 26 patients with positive fungal cultures and positive Musculoskeletal Infection Society (MSIS) criteria for PJI who were treated between 2009 and 2017. We identified 18 patients with total hip arthroplasty (THA) and eight patients with total knee arthroplasty (TKA). The surgical and antifungal treatment, clinical and demographic patient data, complications, relapses, and survival were recorded and analyzed. Results. The median follow-up was 33 months. The success rate was 38.5% (10/26). Fluconazole resistance was found in 15%. Bacterial co-infection was common in 44% of patients for THA and 66% of patients with TKA. Mortality, reoperations, and treatment failure were common complications. Conclusion. Treatment with a two-stage exchange is a possible option for treatment, although fungal infections have a high failure rate. Therapeutic factors for treatment success remain unclear. Cite this article: Bone Joint J 2019;101-B:589–595

Aims. Prosthetic joint infection (PJI) and aseptic loosening in total hip arthroplasty (THA) can present with pain and osteolysis. The Musculoskeletal Infection Society (MSIS) has provided criteria for the diagnosis of PJI. The aim of our study was to analyze the utility of F18-fluorodeoxyglucose (FDG) positron emission tomography (PET) CT scan in the preoperative diagnosis of septic loosening in THA, based on the current MSIS definition of prosthetic joint infection. Patients and Methods. A total of 130 painful unilateral cemented THAs with a mean follow-up of 5.17 years (. sd. 1.12) were included in this prospective study. The mean patient age was 67.5 years (. sd. 4.85). Preoperative evaluation with inflammatory markers, aspiration, and an F18 FDG PET scan were performed. Diagnostic utility tests were also performed, based on the MSIS criteria for PJI and three samples positive on culture alone. Results. The mean erythrocyte sedimentation rate, C-reactive protein, and white cell count were 47.83 mm/hr, 25.21 mg/l, and 11.05 × 10. 9. /l, respectively. The sensitivity, specificity, accuracy, negative predictive value, and false-positive rate of FDG PET compared with MSIS criteria were 94.87%, 38.46 %, 56.38%, 94.59 %, and 60.21%, respectively. The false-positive rate of FDG PET compared with culture alone was 77.4%. Conclusion. FDG PET has a definitive role in the preoperative evaluation of suspected PJI. This the first study to evaluate its utility based on MSIS criteria and compare it with microbiology results alone. However, FDG PET has a high false-positive rate. Therefore, we suggest that F18 FDG PET is useful in confirming the absence of infection, but if positive, may not be confirmatory of PJI. Cite this article: Bone Joint J 2019;101-B:910–914