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

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

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

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

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

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

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

Aim. To provide proof of concept in an in vivo animal model for the prevention of prosthetic joint infection prevention using electric fields along with conventional antibiotic prophylaxis. Corresponding Author: Marti Bernaus. Method. First, we standardized the animal model to simulate implant contamination during the surgical procedure. We then implanted cobalt-chrome prostheses adapted to both knees of two New Zealand White rabbits, under standard aseptic measures and antibiotic prophylaxis with cefazolin. Prior to implantation, we immersed the prostheses in a 0.3 McFarland inoculum of S. aureus (ATCC 25923) for 30 seconds. In the first animal (control), the joint was directly closed after washing with saline. In the second animal (case), both prostheses were treated with electric current pulses for 30 seconds, washed with saline, and the joint was closed. After 72 hours, both animals were reoperated for the collection of periprosthetic tissue and bone samples, and prosthesis removal. In all samples, we performed quantitative cultures prior to vortexing and sonication, as well as prolonged cultures of the sonication broth. We confirmed the absence of contamination by identification with MALDI-TOF (VITEK-MS) and automated antibiotic susceptibility testing of the isolated colonies (VITEK-2). Results. In the “control” animal, we isolated S. aureus in all studied samples. The bacterial count expressed as log10 (cfu/cm2) in the prostheses of the right and left legs was 9.38 and 8.86, respectively. The bacterial count expressed as log10 (cfu/mL) in bone and periprosthetic tissue biopsies was 2.70 and 2.72 in the right leg and 3.24 and 3.87 in the left leg, respectively. In the “case” animal, where an electric field was applied to the implant after placement in addition to cefazolin prophylaxis, all samples (prosthesis, bone, and periprosthetic tissue) were negative, and no isolation of the inoculated strain of S. aureus was obtained after incubation of the sonication broth for 14 days. Conclusions. This in vivo model suggests the potential effectiveness of applying an electric field to a prosthetic implant in combination with cefazolin for the prevention of PJI development, after exposure of the implant to an inoculum of S. aureus (ATCC 25923). Our findings need to be confirmed using a larger sample size

Aim. Rifampicin and fluoroquinolone based therapy is generally considered as first-choice targeted oral antimicrobial therapy for staphylococcal prosthetic joint infections (PJI) treated with debridement, antibiotics and implant retention (DAIR). Alternative equally effective antimicrobial strategies are urgently needed due to toxicity and drug-drug interactions that frequently occur with this strategy. Data from recent clinical studies suggests equipoise for other antimicrobial treatment regimens. The objective of the Rifampicin Combination Therapy versus Targeted Antimicrobial Monotherapy in the Oral Antimicrobial Treatment Phase of Staphylococcal Prosthetic Joint Infection (RiCOTTA)-trial is to evaluate whether monotherapy with clindamycin is non-inferior to rifampicin/fluoroquinolone combination therapy in patients with staphylococcal PJI that are treated with DAIR. Method. The RiCOTTA-trial is a multicenter, non-inferiority, open-label, randomized controlled trial evaluating clindamycin versus rifampicin/fluoroquinolone combination therapy in the oral treatment phase in patients with staphylococcal PJI managed with DAIR. The trial is performed in 16 hospitals in the Netherlands. Eligible patients are adults with staphylococcal knee or hip PJI managed by DAIR. Patients are included one to six days before antibiotic treatment is switched from intravenous to oral therapy. Patients with a contraindication for rifampicin, with a megaprosthesis or who receive intravenous antibiotics for more than three weeks after initial debridement are excluded. Primary outcome is treatment success one year after finishing antimicrobial treatment. Success is defined as the absence of: i. Infection related re-surgery, ii. New episode of antibiotic treatment for infection of the index joint after the initial treatment phase of 12 weeks, iii. Ongoing use of antibiotics for the index joint at the end of follow-up, iv. Death. The estimated treatment success of rifampicin combination therapy is 85% and the monotherapy strategy is considered not inferior when the difference in treatment success will be less than 10%. Enrolment of 158 patients per group (316 in total) is needed to confirm non-inferiority of monotherapy with a power of 80%. The trial is currently open for enrolment. The study is approved by the Medical Ethics Committee Leiden, the Hague, Delft, the Netherlands and registered under EU trial number 2022-501620-26-00 in Clinical Trial Information System. Conclusions. Currently, the RiCOTTTA study is the largest randomised clinical trial that compares targeted oral monotherapy with rifampicin combination treatment for staphylococcal PJI. Noninferiority of monotherapy would result in a change in national PJI guidelines and enable clinicians to use a more patient-tailored approach when considering antibiotics for patients during the oral treatment phase of PJI

Introduction. The burden of prosthetic joint infection (PJI) in total knee arthroplasty (TKA) has been rising in line with the number of primary operations performed. Current estimates suggest an infection rate of 1–2.4%. Two-stage revision has traditionally been considered the gold standard of treatment; however, some studies suggest comparable results can be achieved with single-stage procedures. The potential advantages include less time in hospital, a single anaesthetic, reduced costs, and greater patient satisfaction. Methods. We reviewed data for 72 patients (47 males, 25 females), with a mean age of 71 years (range, 49 to 94), who underwent single-stage revision TKA for confirmed PJI between 2006 and 2016. A standardized debridement protocol was performed with immediate single-stage exchange. All cases were discussed preoperatively at multidisciplinary team (MDT) meetings, which included input from a senior musculoskeletal microbiologist. Patients were not excluded for previous revisions, culture-negative PJI, or the presence of a sinus. Results. The average length of follow-up was 8 years (range, 2 to 13). In total, 65 patients (90.3%) were infection free at most recent follow-up, with seven reinfections (9.7%). Three of these patients with recurrent infections underwent arthrodesis, two underwent re-revision, and two received long-term antibiotics following debridement and implant retention (DAIR). No amputations were undertaken. Conclusions. Single-stage revision for the infected TKA, according to a strict debridement protocol with MDT input, demonstrates reinfection rates comparable with two-stage revision procedures. This is the largest single-surgeon series to date, with extensive follow-up, and supports a growing evidence base for one-stage exchange

Listeria monocytogenes is usually thought of as a bacterial pathogen that causes invasive disease including meningitis and bacteraemia in susceptible hosts. It remains a rare cause of bone and joint infection; there is therefore potential for clinical and laboratory delay in diagnosis and for uncertainty over optimal management. We describe our experience of two such cases of L. monocytogenes prosthetic joint infection to highlight key features in clinical presentation and management. Two case reports of L. monocytogenes prosthetic joint infection are described with reference to previous published cases. A 57 year old woman presented with a 10 day history of severe pain and swelling around a left knee prosthesis which had been implanted as bilateral total knee replacements three years previously. She had a background of rheumatoid arthritis, controlled with prednisolone, methotrexate and ritixumab. Cultures from the left knee isolated L. monocytogenes. The patient was commenced on IV amoxicillin and after 4 weeks underwent 1st stage revision including radical debridement and removal of prosthesis. During the procedure an antibiotic-impregnated spacer (gentamycin/clindamycin with additional vancomycin added in house) was inserted. Antibiotic therapy with intravenous amoxicillin was continued for 2 weeks post-procedure and on discharge the patient was converted to oral amoxicillin for a further 8 weeks. The patient went on to have a 2nd stage revision, making a good recovery. An 85 year old woman presented with an 18 month history of discomfort and recurrent abscesses along the wound line of a left hip prosthesis, implanted over 20 years ago. She had a background of osteoarthritis and bullous phemphigoid, previously on steroid treatment. Fluid from the abscess was aspirated and isolated L. monocytogenes. Due to patient preference and frailty, radical revision was not thought a viable management option. Chronic suppressive therapy with oral amoxicillin was therefore instigated; one year on the infection remains well controlled and discomfort in the left hip has improved. L. monocytogenes has previously been infrequently implicated as a pathogen in prosthetic joint infection; however, there are reports of increasing numbers of cases particularly amongst immunosuppressed individuals. With an expanding at-risk population(1), its importance as a cause of prosthetic joint infection is set to rise in the future. Optimal management has not been well studied; it is likely that the best option combines antimicrobial therapy and prosthetic removal if possible

Background. Treatment of staphylococcal prosthetic joint infection (PJI) usually consists of surgical debridement and prolonged rifampicin combination therapy. Tailored antimicrobial treatment alternatives are needed due to frequent side effects and drug-drug interactions with rifampicin combination therapy. We aimed to assess the effectiveness of several alternative antibiotic strategies in patients with staphylococcal PJI. Methods. In this prospective, multicenter registry-based study, all consecutive patients with a staphylococcal PJI, treated with DAIR or one-stage revision surgery between January 1. st. , 2015 and November 3. rd. , 2020, were included. Patients were treated according to a predefined protocol for PJI. Antimicrobial treatment strategies differed between centers, which was accepted and used as pseudorandomization. Depending on the hospital patients were admitted to, they were treated with either a long-term rifampicin strategy (consisting of 12 weeks rifampicin combination therapy) ore one of several short-term rifampicin strategies, consisting of only five days of rifampicin combination treatment, started immediately postoperative, followed by clindamycin, flucloxacillin or vancomycin monotherapy. Patients were stratified in different groups, depending on the used antimicrobial strategy. Cox proportional hazards models were used to compare outcome between the groups. Results. Two hundred patients were included and, based on the antimicrobial treatment, stratified in one long-term rifampicin group (n=23) or one of the three short-term rifampicin groups: clindamycin (n=56), flucloxacillin (n=47), vancomycin (n=26), other (n=48). Outcome of PJI after DAIR or one-stage exchange was not statistically different between patients treated with long-term rifampicin combination therapy and patients treated with clindamycin or flucloxacillin monotherapy including only five days of rifampicin combination therapy. Moreover, treatment duration was four weeks shorter in the clindamycin-based and flucloxacillin-based groups. Adjusted hazard ratios for failure for patients treated with either flucloxacillin or clindamycin were almost equal to patients treated with long-term rifampicin combination therapy (aHR 1.21, 95%CI 0.34–4.40). Conclusions. A short-term rifampicin strategy with either clindamycin or flucloxacillin and only five days of rifampicin was found to be as effective as traditional long-term rifampicin combination therapy. A randomized controlled trial is needed to further address efficacy and safety of alternative treatment strategies for staphylococcal PJI

INTRODUCTION. Deep infection is a potentially catastrophic complication of joint replacement surgery. Early intervention in suspected prosthetic joint infection in the form of aggressive Debridement and targeted Antibiotics can lead to successful Implant Retention (DAIR). In our centre, we adopt an aggressive approach to suspected prosthetic joint infection, working in a multi-disciplinary team with microbiologists and an infection surveillance team to identify and treat suspected infected cases at the earliest opportunity. OBJECTIVES. To evaluate the efficacy of the treatment of prosthetic joint infection with DAIR. METHODS. All cases of primary prosthetic joint infection between March 2009 and September 2011 were identified. Data was retrospectively collected from root cause analysis data, patient records and hospital electronic results systems. RESULTS. 48 cases of confirmed deep infection were identified from a total of 5037 primary joint replacements. Mean age was 67.3. The mean time between index procedure and return to theatre for debridement was 18 days. 10 patients underwent a second debridement and 3 returned to theatre for a third debridement. Mean total duration of antibiotic treatment was 10.5 weeks with mean duration of intravenous antibiotics 2.7 weeks. There were two early and three late failures on antibiotics. These went on to have successful two stage revision. The mean interval to debridement in failed cases was 15 days. The primary implant was successfully retained in 90% of cases (n=43) at a mean follow up of 30 months. CONCLUSION. DAIR is an effective means of treating early prosthetic joint infection in a multi-disciplinary setting

This study aimed to identify the success rate of debridement, antibiotics and implant retention (DAIR) for prosthetic joint infection (PJI) in a large prospective cohort of patients undergoing total knee arthroplasty (TKA). The ability for different PJI classification systems to predict DAIR success was assessed. A prospective, multicenter study of PJIs occurring between July 2014 and December 2017 in 27 hospitals across Australia and New Zealand was performed. First time PJIs following primary TKA that were managed with DAIR were analyzed. DAIR success was defined as the patient being alive with documented absence of clinical or microbiological evidence of infection and no ongoing antibiotics for the index joint at 2-year follow-up. Multivariate analysis was performed for multiple PJI classification systems to assess their ability to predict DAIR success using their respective definitions of “early” PJI (Coventry ≤1 month, International Consensus Meeting ≤90 days or Auckland <1 year), or as hematogenous versus chronic PJI (Tsukayama). 189 PJIs were managed with DAIR, with an overall success rate of 45% (85/189). Early PJIs had a higher rate of DAIR success when analyzed according to the Coventry system (adjusted odds ratio = 3.85, p = 0.008), the ICM system (adjusted odds ratio = 3.08, p = 0.005) and the Auckland system (adjusted odds ratio = 2.60, p = 0.01). DAIR success was lower in both hematogenous (adjusted odds ratio = 0.36, p = 0.034) and chronic PJIs (adjusted odds ratio = 0.14, p = 0.003) occurring more than one year since the primary TKA. DAIR success is highest when performed in infections occurring within one year of the primary TKA. Late infections had a high DAIR failure rate irrespective of their classification as hematogenous or chronic. Time since primary is a useful predictor of DAIR success

Aim. The aim of this study was to gain insight into the in vivo expression of virulence and metabolic genes of Staphylococcus aureus in a prosthetic joint infection in a human subject. Method. Deep RNA sequencing (RNA-seq) was used for transcriptome profile of joint fluid obtained from a patient undergoing surgery due to acute S. aureus prosthetic joint infection. The S. aureus gene expression in the infection was compared with exponential culture of a S. aureus isolate obtained from the same sample using EdgeR. In addition, the genome of the isolate was sequenced on Miseq, assembled in CLC genomics workbench and annotated by MaGe. Moreover, using nuclear magnetic resonance (NMR) spectroscopy we analysed the metabolites in the joint fluid and in the culture supernatants to determine the biochemical composition of the environments. Results. Antibiotic susceptibility testing by disk diffusion (EUCAST) demonstrated that the strain was susceptible to β-lactams (penicillin and cefoxitin) and macrolides (erythromycin and roxitromycin). This was indirectly confirmed by the annotated genome, because of absence of known resistant genes. The patient showed no signs of improvement during 2-days treatment with antibiotics (different β-lactams and gentamicin) prior to the surgery. The RNA-seq data indicated that the strategy employed by S. aureus to survive and proliferate in the host during antibiotic treatment involved overexpression of various enzymes related to cell-wall synthesis and multidrug efflux pumps. Interestingly, these efflux pumps are only known to be related to fluoroquinolone resistance. Many of the genes encoding virulence factors were upregulated, including toxins and superantigen-like proteins, hemolysins, and immune evasion proteins. A number of chaperones and stress related genes were overexpressed indicating a stress response. Furthermore, the RNA-seq data provided clues of the potential major nutrient sources for the pathogen in vivo. Several amino acid degradation pathways were highly upregulated, e.g. arginine, histidine. Additional carbon sources included N-acetylneuraminate and purine/pyrimidine deoxyribonucleosides as indicated by the upregulation of the genes involved in the degradation pathways of these compounds and higher concentration of these substances in the joint fluid compared to culture supernatants. Conclusions. Our results show that the gene expression pattern of S. aureusin vivo is vastly different from that of an in vitro grown exponential culture, indicating that the pathogen adapts to host environmental conditions by altering gene expression. Finally our study emphasizes the importance of in vivo study in elucidating pathogenesis of S. aureus in prosthetic joint infections

Introduction. In the last couple of years, several synovial biomarkers have been introduced in the diagnostic algorithm for a prosthetic joint infection (PJI). Alpha defensin-1 proved to be one of the most promising, with a high sensitivity and specificity. However, a major disadvantage of this biomarker is the high costs. Calprotectin is a protein that is present in the cytoplasm of neutrophils, and is released upon neutrophil activation. Its value has been established for decades as a (fecal) marker for inflammatory bowel disease. Aim. To determine the efficacy of synovial calprotectin in the diagnosis of a prosthetic joint infection. Methods. We prospectively collected synovial fluid (from hip, knee and shoulder) from patients with a proven PJI (n=15) and from patients that underwent a revision surgery without signs of a PJI (n=19). Patients with an active rheumatoid arthritis and/or gout were excluded from the study. Synovial fluid was centrifuged and the supernatant was used to measure calprotectin, by using a rapid, point of care test. This test was validated for synovial fluid analysis of calprotectin using an ELISA. A Mann-Whitney U test was used to calculate the difference between both patient groups. Results. The median calprotectin level was 899 mg/L (range 28–2120) for PJI versus 22 mg/L (range 0–202) for controls (p < 0.0001). With a cut-off value of 50 mg/L, synovial calprotectin has a high sensitivity of 93%, and a specificity of 84%. The positive and negative predictive values are 82% and 94%, respectively. Conclusions. Synovial calprotectin is a potentially valuable biomarker in the diagnosis of a PJI. With a point of care test, a rapid quantative diagnosis can be made within the operating room (results are obtained within 20 minutes), and could help in the decision making process to re-implant a prosthesis in a one stage procedure. In comparison to the currently available test (to measure alpha defensin-1), the measurement of calprotectin test is much cheaper (500 euro versus 20 euro per sample) and easily to implement in hospitals where this test is already available. Its diagnostic efficacy for exclusively low-grade PJI should be further elaborated

Prosthetic joint infection (PJI) is a severe complication of prosthetic joint implantation, with an estimated incidence of 2.18%. Most frequently used treatment strategy for PJI is a two-stage revision procedure. However there are specific patients with a new or persisting infection after primary or revision surgery where further surgical treatment is not attractive. This may be because of medical or local surgical conditions, or patient's refusal to undergo (further) surgical therapy. For these patients suppressive antibiotic therapy (SAT) may be an alternative treatment. The aim of this study is to describe the clinical and radiological outcome of patients with a PJI of a hip arthroplasty, treated with SAT. Twenty-four patients with a hip arthroplasty treated with suppressive antibiotic therapy for PJI between January 1, 2008 and December 31, 2013 were included. All patients had a proven prosthetic joint infection, either by ≥2 intraoperative cultures or joint aspiration. SAT was defined as treatment with antibiotic therapy for more than three months. Most used antibiotics were doxycycline in 15 patients and cotrimoxazole in six patients. Patients were supposed to have a successful outcome when their prosthesis remained in situ and they had no relapse or new infection. Suppressive antibiotic therapy was considered successful in 15 (62.5%) patients with a mean follow-up of 20.6 months. Two patients (8.3%) had to stop the antibiotic therapy due to adverse effects. The mean duration of the SAT was 20.4 months (range 0.92–92.65 months). Mean modified Oxford hip score of the successfully treated patients at the latest follow up was 35 (range 16–49) and mean Harris hip score 71 (range 40–93). The mean visual analogue scale (VAS) was 16 (range 0–70) in rest, 32 (range 0–85) during exercise and 65 (range 10–100) for satisfaction. Of the 9 patients with an unsuccessful outcome, there was a radiological loosening of the cup in 4 patients. In the group of 15 patients that were considered successful, 2 patients had a radiological loosening of the cup and one patient loosening of the stem. Suppressive antibiotic therapy can be an attractive alternative treatment in selected patients with a prosthetic joint infection of a hip arthroplasty who cannot or will not undergo (further) surgical therapy. Further research with a larger number of patients is required. Also the optimal dosage and duration of suppressive antibiotic therapy and possible resistance to the antibiotic therapy is unknown

Aim. We aimed to compare the in vitro antibacterial activity of Bioactive Glass (BAG) S53P4, which is a compound showing local antibacterial activity, to that of antibiotic-loaded polymethylmethacrylate (PMMA) against multidrug resistant bacteria from osteomyelitis (OM) and prosthetic joint infection (PJI) isolates. Method. We studied convenience samples of multidrug resistant (MDR) microorganisms obtained from patients presenting OM and prosthetic joint infection (PJI). Mixtures containing tryptic soy broth (TSB) and inert glass beads (2mm), BAG-S53P4 granules (0.5–0.8mm and <45 mm) and Gentamicin or Vancomycin-loaded PMMA beads were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus (MR-CoNS), Pseudomonas aeruginosa or Klebsiella pneumoniae isolates. Glass beads (2.0mm) were used as a control. Antibacterial activity was evaluated by means of time-kill curve, through seeding the strains on blood agar plates, and subsequently performing colony counts after 24, 48, 72, 96, 120 and 168 hours of incubation. Differences between groups were evaluated by means of two-way analysis of variance (ANOVA) and Bonferroni's t test. Results. Inhibition of bacterial growth started soon after 48 hours of incubation, reached zero CFU/ml between 120 and 168 hours of incubation for both antibiotic-loaded PMMA and BAG S53P4 groups, in comparison with inert glass (p< 0.05). No difference regarding time-kill curves between antibiotic-loaded PMMA and BAG S53P4 was observed. Moreover, despite no difference was observed between both Vancomycin - or Gentamicin-loaded PMMA and BAG groups, there was statistical difference between the effectiveness of all treatments (BAG included) against gram-positive cocci and gram-negative bacilli, the latter of which requiring longer time frames for the cultures to yield no bacterial growth. Conclusions. BAG S53P4 presented antibacterial properties as much as antibiotic-loaded PMMA for MDR bacteria producing OM and PJI, although presenting differences between its effectiveness against different bacterial groups