Aim. Studies have shown that retention of antibiotic cement spacer in selected elderly patients with low functional demand represents a viable option for periprosthetic joint infections (PJI) treatment. 1,2. . The aim of this study is to compare the efficacy in infection treating among modular taylored preformed and hand-made antibiotic spacers. Our hypothesis is that modular tailored preformed spacer provides a better rate of infection resolution, better radiological and functional outcomes compared to hand-made spacers. Materials and methods. We identified 48 patients treated with antibiotic cement spacer for shoulder chronic infection between 2015 and 2021 in our institution; (13 hand-made spacers and 35 modular tailored preformed spacers). We collected data about comorbidities, associated microorganism, infection resolution, clinical and radiographic evaluation. Results. The mean age at surgery was 63.2 years, (45.8% female − 54.2% male), mean BMI 28.3. The mean time of infection diagnosis after first surgery was 30 months; (31.2% infection after ORIF in proximal humeral fractures, 68.8% PJI after shoulder arthroplasty). The main pathogens were Propionibacterium Acnes (37.5%), Staphylococcus Epidermidis (29.2%), Staphylococcus Aureus (16.7%), negative intraoperative coltures (14.6%), Enterococcus (4.17%), Pseudomonas Aeruginosa (4.17%). The mean time of antibiotic spacer retention was 18 months: 23 patients (47.9%) underwent second stage surgery for prosthesis implantation; 2 removed the spacer because of spacer dislocation, 2 died during follow up; while 21 patients still hold the antibiotic spacer (17 patients in treatment with prefabricated spacers and 4 with self-constructed spacer). The mean value for clinical assessment for patients with modular tailored preformed spacer were: Constant Score 34 – QuickDASH 40 – SST 33 – ASES Score 66 – VAS 2. Patients treated with hand-made spacer registered the following scores: Constant Score 20 – QuickDASH 51 – SST 25 – ASES Score 38 – VAS 6. Two patients presented fracture of the spacer (one hand-made spacer and one tailored preformed). Conclusions. According to our data patients treated with modular tailored preformed antibiotic spacer show better functional outcomes. Patients are more likely to retain the spacer as a permanent implant, avoiding the risks of a second stage surgery in those low-demanding patients, achieving a reasonable satisfying quality of shoulder motion without pain

Aim

Vancomycin-intermediate Staphylococcus aureus (VISA) was associated with persistent infection and treatment failure. To date, two staphylococcal virulence mechanisms have been associated with persistence secondary to host immune evasion and vancomycin therapeutic failure: i) bacterial internalization in non-phagocytic cells and ii) biofilm formation. The present study aimed to compare clinical pairs of isolates composed by VISA and their Vancomycin-Susceptible (VSSA) progenitors toward these bacterial adaptive mechanisms.

Aim. The treatment of chronic orthopedic device-related infection (ODRI) often requires multiple surgeries and prolonged antibiotic therapy. In a two-stage exchange procedure, the treatment protocol includes device removal and placement of an antibiotic-loaded bone cement spacer to achieve high local antibiotic concentrations. At the second stage, further surgery is required to remove the spacer and replace it with the definitive device. We have recently developed a thermo-responsive hyaluronan hydrogel (THH) that may be loaded with antibiotics and used as delivery system. Since the material is bio-resorbable, it does not require surgical removal and may therefore be suitable for use as treatment strategy in a single-stage exchange. This aim of this study was to evaluate gentamicin sulphate (Genta)-loaded THH (THH-Genta) for treating a chronic Staphylococcus aureus ODRI in sheep using a single-stage procedure. Methods. Twelve Swiss-alpine sheep received an IM tibia nail and an inoculation of a gentamicin-sensitive clinical strain of Staphylococcus aureus. After letting a chronic infection develop for 8 weeks, a revision procedure was performed: the implant was removed, the IM canal debrided and biopsies were taken for culture. The IM canal was then filled with 25ml THH-Genta (1% Genta) or left empty (control group) prior to the implantation of a sterile nail. An ultrafiltration probe was placed within the IM cavity to collect extracellular fluid and determine local antibiotic levels for 10 days. Both groups received systemic amoxicillin and clavulanic acid for 2 weeks, followed by 2 weeks without treatment for antibiotic washout. At euthanasia, IM nail, bone marrow, bone and tissue samples were harvested for quantitative bacteriology. Results. All sheep were infected at revision surgery as confirmed by cultures of biopsies and sonication of the IM nail. Local Genta concentrations ranged on average from 830µg/ml postoperatively to below 5µg/ml after 8 days. At euthanasia, S. aureus was detected in 5/5 IM nails, 5/5 bone marrow samples, and 8/25 superficial soft tissue samples in the control group (one control sheep was excluded for having a superinfection). In the THH-Genta group, S. aureus was cultured from 0/6 IM nails, 1/6 bone marrow samples, and 1/30 superficial soft tissue samples. Conclusions. The THH showed a Genta release pattern that started with high local concentrations and decreased to low concentrations within 10 days. Local Genta delivery by THH combined with systemic antibiotics significantly reduced infection rates whereas systemic therapy alone was unable to eradicate infection in any animal

Purpose:. Two-stage revision is the gold standard treatment for chronic periprosthetic infection of the hip or knee. Implantation of a functional antibiotic spacer allows patients the option of two stage revision or living with the spacer in place. Some patients may be satisfied with the activity level that they attain with the functional antibiotic spacer and may avoid the morbidity of a second surgery. Methods:. We retrospectively examined the outcomes of 30 joints in 27 patients treated for chronic periprosthetic infection of the hip or knee at a mean follow-up of 27 months (range 11–46 months). Comparing the patients treated with two-stage revision to those patients living with a functional antibiotic spacer, we used University of California Los Angeles activity scores, modified Harris hip scores, and patient satisfaction measures to answer two main questions: (1) Is there a significant difference in activity level? (2) Is there a significant difference in patient satisfaction? Patient satisfaction was measured on a 1–100 scale with 100 being completely satisfied. Results:. There were no statistically significant differences in the American Society of Anesthesiologists scores between the groups—mean 2.69 in the two-stage group and mean 3.00 in the spacer group (p value 0.255). Statistically significant differences were found between the groups for University of California Los Angeles activity scores—mean 5.3 in the two-stage group and mean 2.8 in the spacer group (p value 0.027). There were no statistically significant differences in modified Harris hip scores—mean 55.6 in the two-stage group and mean 41.6 in the spacer group (p value 0.34). In the subgroup analysis of the modified Harris hip score questions, there was a statistically significant difference in the need for support when ambulating—mean 4.21 in the two-stage group and mean 2.45 in the spacer group (p value 0.024)—and in the distance that can be walked—mean 6.15 in the two-stage group and mean 2.0 in the spacer group (p value 0.005). No statistically significant differences were found in patient satisfaction measures—mean 70.0 in the two-stage group and mean 76.6 in the spacer group (p value 0.65)—though the mean satisfaction measure was higher in the spacer group. Conclusion:. Patients living with a functional antibiotic spacer are less active than patients undergoing a two-stage revision for chronic periprosthetic infection of the hip or knee. Specifically, patients living with a functional antibiotic spacer need more support when ambulating and ambulate shorter distances than patients, who undergo two-stage revision surgery. Despite the decreased activity level, patients living with a functional antibiotic spacer are just as satisfied with the outcome of their joint as those patients treated with a two-stage revision. Patients with modest activity goals may be satisfied to live with a functional antibiotic spacer and to avoid a second surgery

Aim. The purpose of this study is to report the overall infection control rate and prognostic factors associated with acute, hematogenous and chronic PJIs treated with DAIR. Methods. All DAIR procedures performed at 2 institutions from 2009 to 2018 (n=104) were reviewed and numerous data were recorded, including demographics, preoperative laboratory tests, Charleston Comorbidity Index, surgical information and organism culture results. Treatment success was defined according to the criteria reported by Diaz-Ledezma. A multivariable analysis was utilized to identify prognostic factors associated with treatment and a Kaplan-Meier survival analysis was used to depict infection control rate as a function of time. Results. The overall treatment success rate in the current cohort of patients was 67.3% at a median 38.6 (23.5–90.7) months follow-up. Patients with a duration of infectious symptoms greater than 10 days were more likely to fail (P=0.035, odds ratio 8.492, 95% confidence interval 1.159–62.212). There was no difference among acute, hematogenous and chronic infections in terms of failure rate even when time was considered (p=0.161). Conclusion. With careful patient selection, DAIR is a reasonable treatment option for PJI and its use in the setting of chronic infection does not appear to be a contraindication. Performing the DAIR procedure within 10 days of the presentation of symptoms had higher rates of treatment success

Materials & Methods. Chronic osteomyelitis is a complex and challenging condition the successful treatment of which requires a specialist multidisciplinary approach. Prior to tertiary referral to a specialist Orthoplastic Unit, patients often receive multiple courses of antibiotics, in usually unsuccessful attempts, to eradicate infection. This often results in the development of chronic polymicrobial infection. We reviewed the intra-operative cultures of patients treated in our Orthoplastic unit over a 9-year period from 2012–2021 to determine the spectrum of polymicrobial cultures and the relationship to pre-operative cultures. Results. We reviewed the electronic care records and laboratory results of all patients referred to or directly admitted to our unit with a diagnosis of chronic osteomyelitis between 2012–2021. We checked all culture results, antibiotic sensitivities and prescription for treatment. We also checked for any recurrence of infection within 1 year. 60 patients were treated over the 9-year period. 9 upper and 51 lower limbs. The most common referral sources were from the surgical specialties of Trauma & Orthopaedics and Plastic Surgery (62%) while an equal amount came from the Emergency Department and other inpatient medical teams, each making up 15%. A small cohort (8%) developed the infection while still being followed up post fixation. Aetiology of Infection were post fracture fixation 41 (68%), spontaneous osteomyelitis 10 (17%), soft tissue infection 4 (7%). The remaining 5 patients (8%) had a combination failed arthroplasty, arthrodesis and chronic infection from ring sequestrum. 58 patients (97%) had positive cultures with 26 being polymicrobial. 12 cultures were gram negative (G-ve), 11 G+ve 12, 4 anaerobic and 1 Fungal. In 24 patients (40%) the pre-operative cultures and antibiotic sensitivities did not correspond to the intra-operative cultures and sensitivities. 55 patients (92%) required dual or triple therapy with 8% requiring further debridement and extended therapy. 2 (3%) patients had failed treatment requiring amputation. Conclusions. Chronic osteomyelitis is a complex and challenging condition the successful treatment of which requires early referral to a specialist Orthoplastic unit. Less than half of organisms cultured pre-operatively reflect the causative organisms cultured intra-operatively with 52% of these infections being polymicrobial. After initial treatment, 8% of patients will require a further combination of extended antibiotic therapy and surgery to eradicate infection

Aim. Low-grade infections are difficult to diagnose. As the presence of a chronic infection requires extensive surgical debridement and antibiotic treatment, it is important to diagnose a SII prior to surgery, especially when the hardware is revised. We investigated whether serum inflammatory markers or nuclear imaging can accurately diagnose a chronic spinal instrumentation infection (SII) prior to surgery. Method. All patients who underwent revision spinal surgery after a scoliosis correction between 2017 and 2019 were retrospectively evaluated. The diagnostic accuracy of serum C-reactive protein (CRP) and Erythrocyte Sedimentation Rate (ESR), . 18. F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) and Technetium-99m-methylene diphosphonate (99mTc-MDP) 3-phase bone scintigraphy (TPBS) to diagnose infection were studied. Patients with an acute infection or inadequate culture sampling were excluded. SII was diagnosed if ≥ 2 of the same microorganism(s) were isolated from intra-operative tissue cultures. Results. 31 patients were included. The indication for hardware extraction was pseudoarthrosis in the majority of patients (n = 15). 22 patients (71%) were diagnosed with SII. In all infected cases, Cutibacterium acnes was isolated, including 5 cases with a polymicrobial infection. Sensitivity, specificity, PPV and NPV was: 4.5%, 100%, 100% and 30.0% for CRP >10.0 mg/L, 5.5%, 100%, 100% and 29% for ESR > 30 mm/h; 56%, 80%, 83% and 50% for FDG-PET/CT and 50%, 100%, 100% and 20% for TPBS, respectively. Conclusions. The prevalence of SII in patients undergoing revision spinal surgery is high, with Cutibacterium acnes as the main pathogen. No diagnostic tests could be identified that could accurately diagnose or exclude SII prior to surgery. Future studies should aim to find more sensitive diagnostic modalities to detect low-grade inflammation

Aim. To describe the risk factors, microbiology and treatment outcome polymicrobial prosthetic joint infections (PJI) compared to monomicrobial PJI. Methods. Between January 2011 and December 2021, a total of 536 patients were diagnosed with PJI at our institution. Clinical records were revised, and 91(16.9%) had an isolation of two or more pathogens. Age, sex, previous conditions, Charlson comorbidity score, previous surgery, PJI diagnosis and surgical and antibiotic treatment, from the index surgery onwards were reviewed and compared between groups. Results. Polymicrobial PJI success rate was 57.1%, compared to 85.3% of the monomicrobial PJI(p=0.0036). There were no statistically significative differences between acute and chronic infections. In terms of related risk factors, revision surgery(p=0.0002), fracture(p=0.002), tobacco(p=0.0031) and Body Mass Index (BMI) between 20–25(p=0.0021) were associated to monomicrobial PJI, whereas overweight(p=0.005) and obesity(p=0.02) were linked to polymicrobial PJI. Regarding pathogens, the most common microorganism isolated in monomicrobial was S.aureus (33.5%), followed by S. epidermidis(20%) and gram negative bacilli (12.2%); while S. epidermidis(56%), gram negative bacilli (41.8%) and E.colli (30.8%) were the most frequent in the polymicrobial PJI. Enterococci(p=0.0008), S. epidermidis(p=0.007), E.colli (p=0.0008), gram negative bacilli (p=0.00003) and atypical bacteria (p=0.00001) statistically significative linked to polymicrobial PJI; while S.aureus (p=0.018) was related to monomicrobial PJI. Conclusion. Polymicrobial PJI showed worse outcome compared to monomicrobial PJI in our cohort. In terms of risk factors, overweight, obesity and some pathogens like gram negative bacilli, atypical bacteria, enterococci, S. epidermidis and E.colli were associated with Polymicrobial PJI

Survival of sepsis has been documented worldwide, but little is documented about the long-term health outcomes of multifocal sepsis from acute musculoskeletal infection - the first study of its kind in New Zealand. Children admitted to the Paediatric Intensive Care Unit (PICU) from 1. st. January 2002 to 31. st. December 2017 with a musculoskeletal focus of infection were identified from hospital coding data. Notes review from discharge to present day determined survival and morbidity. Present-day clinical assessment of the musculoskeletal and respiratory systems along with questionnaires on health-related quality of life, mental health and sleep were performed. Seventy patients were studied. Seven children died acutely (five Pasifika and two Māori children) indicating 10% mortality. Long-term survival was favourable with no recorded deaths after discharge. Recurrence/chronic infection occurred in 23%, a mean of 1.1 year after discharge. Growth disturbance occurred in 18%, a mean of 3 years after discharge. The hip joint and proximal femur have the worst complications. Children under 2 years are most at risk of long-term disability. No patients had chronic respiratory illness beyond 90 days. Fifteen children had symptoms of acute neurological impairment, three of whom had permanent brain injury. Twenty-six survivors (41%) were assessed a mean of 8.2 years after discharge. Health-related quality of life scores were on par with normative data. Six patients and eight parents screened positive for moderate to severe post-traumatic stress disorder. Paediatric multifocal musculoskeletal sepsis can result in complex illness with long hospital stay and multi-organ complications. Māori and Pasifika children, those under two and those involving the proximal femur/or hip are most at risk. Other outcomes are favourable with no evidence of chronic lung disease or poor quality of life. A period of rehabilitation for children with identified acquired brain injury should be part of discharge planning

This study aimed to identify long-term physical and psychosocial health outcomes in children with overwhelming musculoskeletal sepsis. Children admitted to the Paediatric Intensive Care Unit (PICU) from 1st January 2002 to 31st December 2017 with a musculoskeletal focus of infection were identified. A medical notes review was completed to determine survival and morbidity. Present-day clinical assessment of the musculoskeletal and respiratory systems along with questionnaires on health-related quality of life, mental health and sleep were performed. 70 patients were identified over 15 years. Seven children died acutely (five Pasifika and two Māori children) indicating 10% mortality. Recurrence/chronic infection affected 23%. Growth disturbance affected 18%. The hip joint and proximal femur suffered the worst long-term complications. Children under 2 years most at risk of long-term disability. No patients had chronic respiratory illness beyond 90 days. Fifteen children had symptoms of acute neurological impairment, three of whom had permanent acquired brain injury. Twenty-six survivors (41%) were assessed a mean of 8.2 years (SD 4.5, range 2– 18 years) after discharge. Health-related quality of life scores were on par with normative data. All patients who underwent pulmonary function tests had normal results. Six patients and eight parents screened positive for moderate to severe post-traumatic stress disorder. Paediatric multifocal musculoskeletal sepsis can result in complex illness with multi-organ complications for some children. Māori and Pasifika children are most at risk. Children under 2 years and those with proximal femur and/or hip involvement are most likely to have chronic musculoskeletal sequelae and permanent disability. Other outcomes are favourable with no evidence of chronic lung disease or mean reduced quality of life. A period of rehabilitation for children with identified acquired brain injury should be part of discharge planning

Aim. Osteomyelitis (OM) is a debilitating infection of the bone that originates from hematogenous spreading of microbes or contamination after surgery/fracture. OM is mainly caused by the opportunistic bacterium Staphylococcus aureus (SA), which can evade the host immune response, acquire antibiotic resistance and chronically colonize the musculoskeletal tissue . 1,2. , yet the underlying molecular and cellular processes are largely unclear. This study aimed to characterize the pathogenetic mechanisms of SA-OM with a focus on the long pentraxin 3 (PTX3), a soluble pattern recognition molecule and bone tissue component that is emerging as a new player in osteoimmunology . 3. and a diagnostic marker of periprosthetic joint infections, a common form of OM. 4. . Method. A murine model of OM based on intra-bone injection of SA was developed that closely mimicked surgery/trauma-related OM in humans and allowed addressing the role of PTX3 in gene-modified (Ptx3-/-) animals. Local and systemic infection and inflammation were assessed via microbiology, flow cytometry, histochemistry and microCT techniques. Results. SA-injected mice developed chronic infection with measurable levels of viable bone-resident bacteria up until 30 days from microbial challenge. The infection was confined to the treated limbs only and accompanied by extensive tissue remodelling. The bacterial load was higher in WT than Ptx3. -/-. animals at 6 and 14 days from SA injection. Accordingly, WT mice had enhanced systemic inflammation with expanded innate immune compartment in the spleen and increased serum levels of inflammatory cytokines and chemokines. PTX3 levels were higher in SA- than vehicle (PBS)-injected WT animals both in the serum and bone tissue. Furthermore, administration of a PTX3-targeting antibody reduced the bacterial burden in the bones of SA-injected WT mice. Conclusions. In a mouse model of SA-OM, genetic deficiency of PTX3 protected from infection and inflammation, pointing to this pentraxin as a crucial player in OM pathogenesis and a novel therapeutic target in bone infections. The study was approved by the Italian Ministry of Health (approval n. 520/2019-PR issued on 19/07/2019) and supported by Fondazione Beppe and Nuccy Angiolini

Aim. The objective of this systematic review is to evaluate the current evidence for or against this up-and-coming treatment modality. Method. A comprehensive literature search in accordance with the Preferred Reporting Items for Systematic review and Meta-analysis (PRISMA) guidelines was conducted using PubMed, Embase, MEDLINE and Cochrane databases. Exclusion criteria included patients < 18 years of age, follow-up <11 months, and a score < 6 on the National Institute of Health quality assessment tool. Results. 15 articles, encompassing 631 PJIs in 626 patients, were included in the final analysis, all level IV case series. The quality of many studies was impeded by a retrospective design (14/15), a relative small study population (10 out of 15 studies had less than 50 patients), selection bias, and remarkable heterogeneity in terms of catheter type, antibiotic type, dose and duration of IA antibiotics and techniques of surgical revision. 347 were chronic infections, 66 acute infections and 218 unknown. The majority was treated with single-stage revision with adjuvant IA antibiotic infusion (499/631, 79.1%). The remaining PJIs were treated with stand-alone IA antibiotic infusion (77/631, 12.2%), DAIR with adjuvant IA antibiotic infusion (36/631, 5.7%) or two-stage revision with adjuvant IA antibiotic infusion (19/631, 3.0%). Mean duration of IA antibiotic infusion was 19 days (range 3–50), although most patients received a combination of both IA and systemic (IV or PO) antibiotics. An overall failure rate (defined as failures of infection eradication/total PJIs) of approximately 11% was found. The use of IA antibiotic infusion as a stand-alone treatment was associated with a higher failure rate. In total 117 complications occurred in 631 cases (18.5%). Of these, 71 were non-catheter-related (60.7%) and 46 were catheter-related (39.3%). The most common catheter-related complications were premature loss of the catheter (18/46), developing a fistula (5/46), and elevated blood urea nitrogen (BUN) and creatinine levels (12/46). Conclusions. Due to the lack of comparative studies the (added) benefit of IA antibiotic infusion in the treatment of PJI remains uncertain. From a theoretical point of view it seems likely that is should not be used as a stand-alone treatment. A prospective randomized controlled trial using a well-described infusion protocol is needed to see if the potential benefits justify the increased costs, labour and catheter-related complications of this treatment modality

Aim. Serum parameters continue to be a focus of research in diagnosing periprosthetic joint infections (PJI). Several workgroups have recently proposed serum Albumin-Globulin-Ratio (AGR) as a potential new biomarker. Due to controversies in the literature, its usability in clinical practice remains uncertain. The aim of this study was to assess the value of serum AGR in diagnosing PJI preoperatively, especially in comparison with the well-established marker C-reactive Protein (CRP). Method. From January 2015 to June 2022, patients with indicated revision hip (rTHA) and knee (rTKA) arthroplasty were included in this retrospective cohort study of prospectively collected data. A standardized diagnostic workup was performed using the 2021 European Bone and Joint Infection Society (EBJIS) definition of PJI, excluding CRP. Diagnostic accuracies of serum AGR and CRP were calculated by receiver operating characteristic curve (ROC) analysis. A z-test was used to compare the area under the curves (AUC). Results. A total of 275 patients with rTHA and rTKA were included, 144 joints (52.4%) were identified as septic. Decreased AGR and elevated CRP were strongly associated with PJI, optimal diagnostic thresholds were calculated with 1.253 and 9.4 mg/L, respectively. Sensitivities were 62.5% (95%-confidence interval: 54.3–70.0) and 73.6% (65.8–80.1), and specificities 84.7% (77.5–89.9) and 87.8% (80.9–92.4), respectively. CRP showed a significantly higher AUC than AGR (0.807 (0.761–0.853) and 0.736 (0.686–0.786); p<0.0001). Subgroup analysis of acute versus chronic infections yielded significantly higher diagnostic accuracies in acute PJI for both parameters (p<0.0001). Similar results were observed when focusing on the causative microorganism; a better diagnostic performance was observed in high-virulence PJI compared to low-virulence PJI (p≤0.005). Furthermore, higher AUCs were calculated in knee PJI compared with hip PJI, with a significant difference for AGR (p=0.043). Conclusions. Due to its limited diagnostic accuracy, serum AGR cannot be recommended as an additional marker for diagnosing PJI. Serum parameters are generally unspecific and can be influenced by comorbidities and other foci of infection. Additionally, parameters may remain within normal levels in low-grade PJI. Evaluating AGR, further possible pitfalls must be considered, for example an increased latency until bottom values are reached and the impact of malnutrition

Aim. The gold standard treatment for late acute hematogenous (LAH) periprosthetic joint infection (PJI) is surgical debridement, antibiotics and implant retention (DAIR). However, this strategy is still controversial in the case of total knee arthroplasty (TKA) as some studies report a higher failure rate. The aim of the present study is to report the functional outcomes and cure rate of LAH PJI following TKA treated by means of DAIR at a long-term follow-up. Method. A consecutive prospective cohort consisting of 2,498 TKA procedures was followed for a minimum of 10 years (implanted between 2005 and 2009). The diagnosis of PJI and classification into LAH was done in accordance with the Zimmerli criteria (NEJM 2004). The primary outcome was the failure rate, defined as death before the end of antibiotic treatment, a further surgical intervention for treatment of infection was needed and life-long antibiotic treatment or chronic infection. The Knee Society Score (KSS) was used to evaluate clinical outcomes. Surgical management, antibiotic treatment, the source of infection (primary focus) and the microorganisms isolated were also assessed. Results. Among the 2,498 TKA procedures, 10 patients were diagnosed with acute hematogenous PJI during the study period (0.4%). All those 10 patients were operated by means of DAIR, which of course included the polyethylene exchange. They were performed by a knee surgeon and/or PJI surgeon. The failure rate was 0% at the 8.5 years (SD, 2.4) follow-up mark. The elapsed time between primary total knee replacement surgery and the DAIR intervention was 4.7 years (SD, 3.6). DAIR was performed at 2.75 days (SD 1.8) of the onset of symptoms. The most common infecting organism was S. aureus (30%) and E. coli (30%). There were 2 infections caused by coagulase-negative staphylococci and 2 culture-negative PJI. All culture-positive PJI microorganisms were susceptible to anti-biofilm antibiotics. The source of infection was identified in only 3 cases. The mean duration of antibiotic treatment was 11.4 weeks (SD 1.9). The postoperative clinical outcomes were excellent, with a mean KSS of 84.1 points (SD, 14.6). Conclusions. Although the literature suggests that TKA DAIR for acute hematogenous periprosthetic joint infection is associated with high rates of failure, the results presented here suggest a high cure rate with good functional outcomes. Some explanations for this disparity in results may be the correct diagnosis of LHA, not misdiagnosing acute chronic PJI, and a thorough debridement by surgeons specialized in PJI

Aim. We aimed to assess the incidence and the outcome of Gram-negative prosthetic-joint infections (PJI) in 3 international tertiary hospital. Method. We included patients with Gram-negative PJI at Humanitas Clinical and Research Hospital (Milan, Italy), Centre Hospitalier Universitaire Vaudois (Lausanne, Switzerland) and Hospital Parc de Salut Mar (Barcelona, Spain) between 2014 and 2018 in a retrospective cohort. We described the treatment's success rate according to Gram-negative species and type of surgical procedure. Results. In the present cohort we have 780 PJI out of which 71 (9.1%) were caused by Gram-negative bacteria (polymicrobial infection 30%, Escherichia coli 25%, Pseudomonas aeruginosa 20%, Proteus spp. 4%, Klebsiella spp. 3%, Morganella morganii 3%, Enterobacter 3%, others 12%). Gram-negative PJI were more common in females (60%) than males (40%). Sixty percent had a hip infection, 40% a knee infection, the median age was 74 years and the median ASA score was 3. It was a chronic infection in 60% of the cases and an acute one in 40%. Two-step exchange was performed in 55%, débridement and retention (DAIR) in 30%, one-step exchange in 11% and implant removal without replacement in 4% of the patients. The overall treatment success rate was 89%. The success rate was better for two-step exchange (95%) compared to DAIR (81%) and one-step exchange (87%) (p=0.068). The median antibiotic duration was 68 days and ciprofloxacin was used in 70% of the cured patients versus in 88% of the failures (p=0.388). Infections caused by Escherichia coli were associated with a lower success rate (83%) especially compared to Pseudomonas aeruginosa (93%) and polymicrobial infections (90%) (p=0.358). Finally, the success rate was better in knee PJI compared to hip PJI (97% versus 83%, p=0.121) and in females compared to males (93% versus 82%, p=0.121). Conclusions. The treatment's success of Gram-negative PJI is comparable to reported rates for all bacteria. However, our results suggest that surgical management with two-step exchange might be useful in selected patients’ groups such as those with Escherichia coli PJI. Moreover, ciprofloxacin use seems not to improve cure rate

Aim. Staphylococcus epidermidis (S. epidermidis) is one of the main pathogens responsible for bone and joint infections especially those involving prosthetic materials (PJI). Although less virulent than S. aureus, S. epidermidis is involved in chronic infections notably due to its ability to form biofilm. Moreover, it is frequently multiresistant to antibiotics. In this context, the development of additional or alternative antibacterial therapies targeting the biofilm is a priority. Method. The aim of this study was to evaluate in vitro the activity of phage lysin exebacase (CF-301) against biofilms formed by 19 S. epidermidis clinical strains responsible for PJI. We determined the remaining viable bacteria inside the biofilm (counting after serial dilution and plating) and the biomass (bacteria and extracellular matrix, using crystal violet staining) after 24h of exposition to exebacase at different concentrations, alone (0.05; 0.5; 5; 50 and 150 mg/L) or in combination (5, 50 and 150 mg/L) with antibiotics commonly used to treat multi-resistant S. epidermidis PJI (rifampin (1 mg/L), vancomycin (10mg/L) and daptomycin (10mg/L)). In this study, synergy was defined as a significantly higher effect of the association in comparison to the sum of the effect of each molecule. Results. Exebacase showed a dose-dependent reduction of biomass, ranging from 11 % at 0.5 mg/L to 66 % at 150 mg/L. Exebacase showed a significant bactericidal activity at 50 and 150 mg/l, with a mean decrease of the inoculum of 0.94 and 1.7 log, respectively. In addition, synergistic effects were observed in association with i) rifampin (1 mg/L) showing a mean decrease up to 84% of the biomass and 3.5 log CFU at 150 mg/L of exebacase, ii) vancomycin (10 mg/L) showing a mean decrease up to 81% of the biomass and 2.82 log CFU at 150 mg/L of exebacase, iii) and daptomycin (10 mg/L) showing a mean decrease up to 85% of the biomass and 3.1 log CFU at 150 mg/L of exebacase. Conclusions. Exebacase showed, in vitro, synergistic activity with antibiotics against S. epidermidis biofilms. It is a promising adjuvant therapy to rifampin, vancomycin and daptomycin in the context of PJI. Further studies are needed, in vitro to understand the mechanism of action on S. epidermidis biofilm and the heterogeneity of strain behaviour and in vivo to confirm the present data

Aim. To retrospectively evaluate infection eradication rate of DAIR procedures performed in our tertiary referral center. We analyzed whether the outcome was influenced by time of infection after arthroplasty, previous surgery or causative pathogen. Methods. We retrospectively collected data of 81 patients treated with DAIR for periprosthetic joint infections after hip (n=48) and knee (n=33) arthroplasty between 2011 and 2017. Patients were divided into 3 groups: acute early infections (occurring <4 weeks, 29 cases), late chronic infections (occurring >4 weeks postoperative, 49 cases) and acute haematogenous infections (occuring >3 months after surgery with symptoms less than 4 weeks, 3 cases). Primary outcome was successful infection eradication after treatment within one year. Eradication failure was determined as unplanned subsequent surgery because of persistent infection, use of suppressive antibiotics or signs of infection at one year follow-up. Results. Patients treated with DAIR (n=25) after previous infection treatment such as DAIR, one- or a two-stage revision showed a success of 44% versus 71% in patients treated with DAIR after primary arthroplasty (n=56). A majority of the patients had a monomicrobial PJI (72%) versus polymicrobial (22%), while 6% were culture negative. Acute early infections, late chronic infections and hematogenous infections had a success rate of 66%, 61% and 67% respectively. The most common pathogen in monomicrobial infections was Staphylococcus aureus (19%) followed by Staphylococcus epidermis (12%). Patients with Staphylococcus aureus infections had a success rate of 60% compared to 80% for Staphylococcus epidermis infections. Conclusion. Our study shows that good results can be expected when DAIR is performed in patients with acute and late chronic PJI even in a more difficult-to-treat patient population. Interestingly, in 4 out of 10 patients who received a secondary DAIR procedure, the implant could still be retained. Lastly, specific causative organisms can lead to a lower success rate of DAIR

Aim. Although established serum inflammatory biomarkers, such as serum C-reactive protein (CRP) and serum white blood cell count (WBC), showed low accuracies in the literature, they are still commonly used in diagnosing periprosthetic joint infections (PJI). For a sufficient preoperative diagnosis novel more accurate serum parameters are needed. The aim of our study was to evaluate the performances of the established and novel routinely available serum parameters in diagnosing periprosthetic joint infections when using the proposed European Bone and Joint Infection Society (pEBJIS) criteria. Method. In this retrospective study, 177 patients with an indicated revision surgery after a total joint replacement were included from 2015 to 2019. The easily accessible and routinely available serum parameters CRP, WBC, the percentage of neutrophils (%N), the neutrophils to lymphocytes ratio (NLR), fibrinogen and the platelet count to mean platelet volume ratio (PC/mPV) were evaluated preoperatively. The performances were examined via receiver operating characteristic (ROC) curve analysis (AUC). The curves were compared using the z-test. Seventy-five cases (42%) showed a PJI based on the pEBJIS-criteria. Results. The sensitivities of serum CRP (cut-off: ≥10mg/L), WBC (≥10×10^9 cells/L), %N (≥69.3%), NLR(≥ 3.82), fibrinogen (≥ 457 mg/dL), and PC/mPV (≥ 29.4) were calculated with 68% (95% CI: 57–78), 36% (26 – 47), 66% (54 – 76), 63% (51 – 73), 69% (57 – 78), and 43% (32 – 54), respectively. Specificities were 87% (79 – 93), 89% (81 – 94), 67% (57 76), 73% (63 – 81), 89% (80 – 93), and 81% (72 – 88), respectively. Serum CRP and fibrinogen showed better performances than the other evaluated serum parameters (p<0.0001). The median serum CRP (17.6 mg/L) in patients with PJI caused by a low virulence microorganism was lower compared with infections caused by high virulence organisms (49.2 mg/L; p=0.044). Synovial fluid leucocyte count and histology showed better accuracies than serum CRP, serum WBC, %N, NLR, serum fibrinogen, and PC/mPV (p<0.0001). Conclusions. Although serum CRP and fibrinogen showed the best performances among the evaluated serum inflammatory markers, their results should be interpreted with caution in clinical practice. Serum parameters may remain normal in chronic infections or may be elevated in patients with other inflammatory conditions. In addition, they also correlated poorly with synovial fluid leukocyte count and histology. Therefore, serum parameters are still insufficient to confirm or exclude a periprosthetic joint infection. Hence, they can only be recommended as suggestive criteria in diagnosing PJI

Aim. Shoulder prosthesis chronic infection is a rare but serious complication, likely to lead to re-interventions and poor functional outcome. Two-stage exchange surgery is considered the standard procedure by most authors. Our hypothesis was that one-stage revision procedure is a valid therapeutic option in the management of chronic infections of shoulder arthroplasty. Method. This was a mono-center retrospective cohort study. All patients who underwent, during the inclusion period, a one-stage revision procedure for a chronic infection of shoulder arthroplasty were included. All patients underwent clinical evaluation (Constant-Murray score), radiological examination (standard X-rays) and a blood test (Complete Blood Count and C-reactive protein), at a minimal one-year follow-up. Primary endpoint of this study was the infectious outcome and secondary endpoints were the functional and radiographic outcomes. Results. 16 shoulder prosthesis in 14 patients (5 females, 9 males) were included. Mean time between primary prosthesis implantation and exchange surgery was 40 months (1–145). Mean follow up was 30,5 months. The principal micro-organism involved was Propionibacterium acnes (9/16) and multiple organisms were found in 6 patients. In 14/16 (87,5%) shoulders, we found no sign of persistent infection at last follow-up. 2/16 (12,5%) shoulders were considered as still infected. On these 2 patients still infected, one refused further revision and the other was not in a good enough medical condition to undergo another procedure. 2 patients required an additional one-stage procedure for a new infection (new pathogen) after a period of two years, both free of infection at last follow-up. At last follow-up, mean Constant score was 54,8 (23–82). 7/14 (50%) patients were satisfied or very satisfied with the global fonctionnal result. Conclusions. One-stage revision procedure seems to be a valid therapeutic option in the management of infected shoulder prosthesis, as it allowed us to eradicate the infection in 87,5% patients in our serie, with a fair clinical result

Aim. The aim of the study was to assess the accuracy of the alpha defensin lateral flow test for diagnosis of periprosthetic joint infection (PJI) using an optimized diagnostic algorithm and three classification systems. In addition, we compared the performance with synovial fluid leukocyte count, the most sensitive preoperative test. Method. In this prospective multicenter study we included all consecutive patients with painful prosthetic hip and knee joints undergoing diagnostic joint aspiration. Alpha defensin lateral flow test was used according to manufacturer instructions. The following diagnostic criteria were used to confirm infection: Musculoskeletal Infection Society (MSIS), Infectious Diseases Society of America (IDSA) and Swiss orthopedics and Swiss Society of Infectious Diseases (SOSSID). In the latter, PJI was confirmed when at least one of following criteria applied: macroscopic purulence, sinus tract, positive cytology of joint aspirate (>2000 leukocytes/μl or >70% granulocytes), histological proof of acute inflammation in periprosthetic tissue, positive culture (from aspirate, tissue or sonication fluid). Infection was classified as chronic, if symptom duration was more than 3 weeks or if infection manifested after more than 1 month after surgery. The sensitivity and specificity of the alpha defensin lateral flow test and leukocyte count in synovial fluid were calculated and compared using McNemar Chi-square test. Results. Of 151 included patients evaluated for painful prosthetic joints (103 involved knees, 48 hips), the median patient age was 69 years (range, 41–94 years) and 75 patients were female. Systematically evaluating the included patients according to the different diagnostic criteria, MSIS and IDSA revealed both 33 patients with PJI (22%), whereas SOSSID disclosed 47 septic failures (31%), among them 36 chronic infections (77%). Sensitivity of the test was 79% when applying MSIS criteria, 70% with IDSA criteria and 57% with SOSSID criteria. Specificity ranged from 96% (IDSA) to 98% (MSIS) and 99% (SOSSID). Applying the most stringent definition criteria (SOSSID), leukocyte count showed significantly higher sensitivity than the alpha defensin lateral flow test (91% vs. 57%, p<0.001), especially in chronic infections (88% vs. 48%, p<0.001.) In acute infections, both tests detected all infection cases. Processing turnaround time was shorter in Alpha defensin lateral flow test than automated leukocyte count (10 min vs. 2–4 hours). Conclusions. Semi-quantitative alpha defensin test was rapid and highly specific for diagnosing PJI (> 95%). However, sensitivity was limited, especially when applying definition criteria including also low grade infections (SOSSID criteria). Therefore, the alpha defensin lateral flow test does not allow a reliable exclusion of PJI, especially not in chronic infections but may be used as confirmatory test