Orthopedic Device-Related Infections (ODRIs) are a major medical challenge, particularly due to the involvement of biofilm-encased and multidrug-resistant bacteria. Current treatments, based on antibiotic administration, have proven to be ineffective. Consequently, there is a need for antibiotic-free alternatives. Antimicrobial peptides (AMPs) are a promising solution due to their broad-spectrum of activity, high efficacy at very low concentrations, and low propensity to induce resistance. We aim to develop a new AMP-based chitosan nanogel to be injected during orthopedic device implantation to prevent ODRIs. Chitosan was functionalized with norbornenes (NorChit) through the reaction with carbic anhydride and then, a cysteine-modified AMP, Dhvar5, a peptide with potent antibacterial activity, even against methicillin-resistant Staphylococcus aureus (MRSA), was covalently conjugated to NorChit (NorChit- Dhvar5), through a thiol-norbornene photoclick chemistry (UV= 365 nm). For NorChit-Dhvar5 nanogels production, the NorChit-Dhvar5 solution (0.15% w/v) and Milli-Q water were injected separately into microfluidic system. The nanogels were characterized regarding size, concentration, and shape, using Transmission Electron Microscopy (TEM), Nanoparticle Tracking Analysis (NTA) and Dynamic light scattering (DLS). The nanogels antibacterial properties were assessed in Phosphate Buffer (PBS) for 6 h, against four relevant microorganisms (Pseudomonas aeruginosa, S. aureus and MRSA, and in Muller- Hinton Broth (MHB), 50% (v/v) in PBS, supplemented with human plasma (1% (v/v)), for 6 and 24 h against MRSA. The obtained NorChit-Dhvar5 nanogels, presented a round-shaped and ∼100 nm. NorChit- Dhvar5 nanogels in a concentration of 10. 10. nanogels/mL in PBS were capable of reducing the initial inoculum of P. aeruginosa by 99%, S. aureus by 99%, and MRSA by 90%. These results were corroborated by a 99% MRSA reduction, after 24 h in medium. Furthermore, NorChit-Dhvar5 nanogels do not demonstrate signs of cytotoxicity against MC3T3-E1 cells (a pre-osteoblast cell line) after 14 days, having high potential to prevent antibiotic-resistant infection in the context of ODRIs

Abstract Background. The treatment of bone and joint infections (BJI) involving multi-drug resistant bacteria remains a challenge. MDR Staphylococcus epidermidis (MDRSE) clones, resistant to methicillin, clindamycin, levofloxacin, rifampicin and even linezolid, have been reported worldwide. The interest of delafloxacin (DFX), theoretically active on MRSA, remains to be evaluated with respect to MDRSE. Purpose. Our objective was to evaluate during a retrospective multicenter study the DFX minimal inhibitory concentrations (MICs) and compare its efficacy between ofloxacin-susceptible and ofloxacin-resistant S. epidermidis clinical strains involved in BJI. Methods. In this multicenter retrospective study (Reference centers from the West part of France, CRIOGO), 529 strains were collected mostly from BJI. DFX MICs were determined by using a 0.5 Mc Farland bacterial inoculum on Mueller-Hinton agar plates with gradient strips incubated for 24h at 35°C. For S. aureus, breakpoints differentiate skin and soft tissue infections from other infections. Breakpoints followed 2022 EUCAST criteria, with S. aureus values adopted for S. epidermidis. Results. Of the 529 strains collected, 355 were from prosthetic infections, 159 from synthetic infections and 15 from non-device infections. 152 strains were susceptible to ofloxacin (110 males vs 42 females) and 377 resistant (210 vs 167). As presented in Figure 1, all the ofloxacin-susceptible strains presented a DFX MIC ≤0.006mg/L. Resistant strains presented a double population distribution, with 3.7% categorized susceptible according to skin and soft tissues infections breakpoint, against 88.9% according to other breakpoint infections (0.016 or 0.25mg/L respectively). Conclusion. DFX shows excellent activity against ofloxacine-susceptible strains. Concerning the ofloxacin-resistant strains, more than 80% strains or less than 10% can be considered as DFX-susceptible depending on the breakpoints used. Further clinical studies are needed to validate the real breakpoints that must be used in MDRSE BJI, allowing a microbiological cure and a favourable clinical outcome. For any tables or figures, please contact the authors directly

Abstract. Background. Distinction between foot and ankle wound healing complications as opposed to infection is crucial for appropriate allocation of antibiotic therapy. Our aim was to evaluate the diagnostic accuracy of white cell count (WCC) and C-reactive protein (CRP) as diagnostic tools for this distinction in the non-diabetic cohort. Methods. Data were reviewed from a prospectively maintained Infectious Diseases Unit database of 216 patients admitted at Leicester University Hospitals – United Kingdom between July 2014 and February 2020 (68 months). All diabetic patients were excluded. For the infected non-diabetic included patients, we retrospectively retrieved the inflammatory markers (WCCs and CRP) at the time of presentation. Values of CRP 0–10 mg/L and WCC 4.0–11.0 ×109 /L were considered normal. Results. 25 patients met our inclusion criteria. Infections were confirmed microbiologically with positive intra-operative culture results. 7 (28%) patients with foot osteomyelitis (OM), 11 (44%) with ankle OM, 5 (20%) with ankle septic arthritis, and 2 (8%) patients with post-surgical wound infection were identified. Previous bony surgery was identified in 13 (52%) patients. 21 (84%) patients did have raised inflammatory markers while 4 (16%) patients failed to mount an inflammatory response even with subsequent debridement and removal of metalwork. CRP sensitivity was 84%, while WCC sensitivity was only 28%. Conclusion. CRP had good sensitivity, whereas WCC is a poor inflammatory marker in the detection of such cases. In presence of a clinically high level of suspicion of foot or ankle infection, a normal CRP should not rule out the diagnosis of OM

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

Staphylococcus aureus osteo-articular infections (OAI) are frequently accompanied by blood stream infections (BSI) diagnosed by positive blood culture (BC). Microbiological protocols in adults advise prolonged intravenous antibiotics and repeat BC 48-hourly in the presence of a BSI, however evidence to support the systematic employment of these guidelines in paediatric patients is lacking. We aimed to determine whether there was an increased incidence of orthopaedic and systemic complications in patients with s aureus BSI, and whether a shorter duration of intravenous antibiotics was associated with the development of complications.

Following ethical approval, the departmental surgical database was searched for patients that underwent surgery for acute OAI over a 5-year period. Patients with no sample taken for BC were excluded, as were those with other or no organisms identified from any site. Demographic and clinical data were captured, including duration of IV antibiotics and development of complications. Statistical significance was set at p<0.05.

Following exclusions, 44 patients with a median age of 85 months remained to be analysed. Thirty patients (68%) had a positive BC. A positive BC was associated with a higher rate of systemic complications (p=0.026) but not orthopaedic complications (p=0.159). Patients who had developed any complication had a significantly longer duration of IV antibiotic treatment compared to those without complications (p<0.001). The presenting CRP levels were significantly higher in patients that developed complications (p=0.004).

Patients with staphylococcal BSI in association with an OAI are at increased risk of developing systemic complications. In our cohort, a shorter duration of antibiotic use was not associated with the development of complications, which does not support the systematic use of long courses of IV antibiotics in s aureus BSI. Further research will be required to determine the ideal protocol for these patients.

Aim. National Joint Replacement Registries, which are important sources for periprosthetic joint infection (PJI) data, report an average PJI incidence ranging from 0.5 to 2.0%. Unfortunately, national registries including the Dutch Arthroplasty Register (LROI), are not specifically designed to register PJI. In the Netherlands, the LROI is a nationwide population-based registry with an overall completeness of more than 95%. 3. To ensure usability and reliability of PJI data from the LROI, it is important to evaluate the quality and completeness of these data. From 2013 onwards, eight hospitals in the South-East of the Netherlands, collected their PJI data in a detailed regional infection cohort (RIC), specifically designed for this purpose. This study aimed to determine the accuracy and completeness of PJI registration (hip and knee arthroplasty) in the LROI, by comparing the LROI with the RIC. Method. All patients registered with an acute PJI in the RIC between 2014–2018 were selected for the study and were matched with the LROI. According to the Workgroup of American Musculoskeletal Infections Society (MSIS), an acute PJI was defined as at least two phenotypically identical pathogens, isolated in cultures from at least two separate tissues, obtained from the affected peri-prosthetic tissue during the DAIR treatment (debridement, antibiotics, irrigation, and retention). Only PJI occurring within 90 days after primary hip or knee arthroplasty were included. The LROI data and completeness was based on the entered procedures and documented reason for revision infection, which was not specially based on the MSIS criteria. After checks on missing and incorrectly data, the completeness of registration in the LROI was calculated by comparing the number of registrations in the LROI with data from the RIC (gold standard). Results. Of the 639 primary total hip and knee arthroplasty with a suspected PJI registered in the RIC between 2014–2018, 352 cases met the definition of acute PJI. The overall incidence was 1%. When compared with the LROI, 164 of these cases were also registered in the LROI as PJI revision, resulting in a 53% underestimation of PJI for the LROI. Conclusions. LROI data on acute PJI shows a significant underestimation, which is comparable to scarce other literature sources. To ensure reliability and usability of national PJI data, a specifically part of the LROI has to be designed for registering PJI similar to the regional cohort

Aim. was to analyze infections after bone tumour surgery. Method. 1463 patients treated from 1976 to 2007 were analized: 1036 with resection and prostheses in the lower limbs, 344 with resection and prostheses in the upper limbs, 83 with surgery for sacral tumours. Infections were analyzed for time of occurrence (“postoperative” in the first 4 weeks from surgery, “early” within 6 months, and “late” after 6 months), microbic agents, treatment, outcome. Results. In lower limbs, infections occurred in 80 cases (7.7%): generally monomicrobial, caused by gram positives, postoperative in 9, early in 12, late in 59 cases. Treatment was “two stage” in 73, “one stage” in 4, primary amputation in 3. Revisions for infection were successful in 63 patients (79%), while 17 patients were amputated (21%). In upper limbs, infections occurred in 20 cases (5.8%): generally monomicrobial, caused by gram positives (88.5%), postoperative in 2 cases, early in 7, late in 11. “Two stage” treatment was attempted in all cases, but only in 3 prosthesis was re-implanted, since the cement spacer yelded similar function. No infections were observed in 28 intralesional excisions of sacral giant cell tumours. Infection occurred in 23/52 resected sacral tumours (44%) (Three patients died postoperatively were excluded from this group): postoperative in 16 cases and early in 7, caused by gram negatives in 62% and multimicrobial in 74%. Surgical debridements associated with antibiotic therapy according to coltures cured infection in all cases. Conclusion. Infection is a severe complication in orthopedic oncology. Its incidence in the extremities (7.7% and 5.8%) is lower than after sacral surgery (44%). It is influenced by chemotherapy and by the presence of foreign bodies. Infections were mostly late, monomicrobial, gram positive in extremities, while early, multimicrobial and gram negative in sacral surgery

Introduction: A multiplicity of factors can increase the risk of nosocomial infection in polytraumatized patients. Infections in the hospital environment are still a serious public health hazard. Nonetheless, only a few studies have been published on nosocomial infections in poly-traumatized pediatric patients. Materials and methods: A 4-month prospective study was carried out of patients admitted to the traumatology department and to the pediatric intensive-care unit between July and November 2003 in order to assess all the procedures the patients were subjected to. Infections were considered to be nosocomial when they appeared 72 hours after admission. Results: 121 patients were included in the study. 77% (93) were boys and 23% (28) girls, with a mean age of 10.6 years. The number of infected patients was 6 (5%) and the number of episodes of nosocomial infection diagnosed was 12. 33% of infected patients had a single episode and 67% had two or more infections. When considering the intrinsic risk factors considered in the study one should mention that 10% of patients who were admitted were in a coma, 4,1% had a respiratory syndrome and 2% were diagnosed as obese. The most frequently isolated micro-organisms in this group of patients were Gram positive bacteria (50%), while the most common pathogen was coagulase-negative staphylococcus (85,7%). Conclusions: The paper reveals the profile of nosocomial infections in ploytraumatized pediatric patients in our hospital environment and defines their connection with the use of invasive measures as well as with the length of the patient’s hospital stay

Background: In recent years there has been an increase in the insertion of prosthetic devices in orthopaedics. In spite of improvements in surgical techniques and antibiotic prophylaxis, the absolute number of infectious complications is high. Infections have a negative impact in patient’s quality of life and have high costs of management. Patients and Methods: Retrospective analysis of diagnosis, aetiology, and therapy of prosthetic devices infections observed from 1985 to 1999 in the operative unit for diagnosis and treatment of Infections in orthopaedics of Ospedale S. Corona- Pietra Ligure (SV). Results: During the study period, 251 patients with infected hip prosthesis and 133 with infected knee prosthesis had been treated. Diagnosis of infection was made by means of clinical features supported by x-ray, MRI, CT scan, ultrasonography and radio-nuclide scan. Aetiology was established by microbiological culture and histology. The majority of cases were single agent infections due to Gram-positives, especially S. aureus and S epidermidis, isolated in 41% of hip and 53% of knee prosthesis infection, while P. aeruginosa represented the most frequently isolated Gram-negative (3% in hip prosthesis and 10.6 % in kne prosthesis). Polymicrobial infections (with constant presence of S. aureus and/or S. epidermidis) accounted for 8% of hip and 7% of knee prosthesis infections. Treatment was represented by prolonged antibiotic administration (at least 8 weeks) associated with surgical debridment inacute infections, and two-stage exchange in chronic infections. In 23 hip infections in patients in poor clinical conditions or in suspected persistence of latent infection a new prosthesis was not replaced and Girdlestone’s hip arthroplasty was performed. Conclusions: Gram-positives are the main cause of orthopaedic infections but Gram-negatives, especially P aeruginosa, are often isolated. The treatment must necessarily be combined: antibiotic therapy and surgical treatment. Only in presence of optimal conditions a new prosthesis can be replaced

Introduction. Polymicrobial infections are expected to complicate the treatment of bone and joint infections. Septic nonunions often occur after initial open fractures, which prophylactically receive broad-spectrum antibiotics. However, no data that describes frequencies of polymicrobial infections and pathogens evident in course of the treatment of septic nonunions is published. Therefore, this study aims at investigating the frequency and pathogen types in polymicrobial infections. Methods. Surgically treated Patients with long bone septic nonunion admitted between January 2010 and March 2018 were included in the study. Following parameters were examined: age, gender, American Society of Anesthesiologists (ASA) score, body mass index (BMI), and anatomical location of the infected nonunion. Microbiological culture data, polymerase-chain-reaction results of tissue samples, sonication, and joint fluid of the initial and follow-up revision surgeries were assessed. No exclusion criteria were determined. Results. The study encompassed 42 patients with a mean age of 53.9 ± 17.7 years (range, 23 – 93). Sixteen (38.1%) patients were female. In 46.3% of the patients open fractures led to septic nonunion. Twenty-six nonunions occurred at the tibia or fibula, 11 were localized at the femur, 2 at the humerus and 3 at the forearm. Only 2 patients were assessed as ASA type 1, while 26 were ASA type 2 and 12 patients ASA type 3. Mean number of performed surgeries was 6 ± 0.67 (range 2 – 21). In 6 patients (14.3%) polymicrobial infection were evident. A change of evidenced pathogens in course of the treatment occurred in 21 patients (50%). In 16 patients (38.1%) previously detected bacteria could be evidenced by microbial testing after further revision surgery. Staphylococcus aureus was most often evident (n=34, 30.6%), followed by Enterococcus species (n=25, 22.5%) and Staphylococcus epidermidis (n=18, 16.2%). Five Staphylococcus aureus were resistant to methicillin (MRSA). In patients without polymicrobial infection or further germ detection in course of the treatment 86.4% of the infections were due to Staphylococcus species. Patients with change of detected pathogens and polymicrobial infections suffered from more enterococci infections. Infections due to streptococci and gram-negative bacteria could only be evidenced in patients with polymicrobial infection and pathogen change in course of the treatment. Conclusion. The observed difference of microbiological patterns in septic nonunion may help to facilitate adjuvant local and systemic antibiotic treatment in septic nonunion patients. Reasons for the observed difference of microbiological patterns and its influence on patient outcome have still to be elucidated

The total hip arthroplasty (THA) is an effective operation for the restoration of the hip function. The number of operations is steadily climbing and is going to reach new heights in the future. The most devastating complication is the deep infection of the joint and has to be treated with a total revision of the prostheses. The risk factors for an infection play a very important role in the preoperative assessment of the patient and for the antibiotic treatment. There are many different opinions on which risk factors are associated with the development of a deep infection in the literature. Our goal was to analyze and find the risk factors, which matter most in the clinical treatment of patients. We searched the database “PubMed” and “Embase” with the keywords: „(((hip AND infection)) AND (arthroplasty OR replacement)”. With the help of check lists and limits we extracted the most viable studies for our research. Risk factors associated with a deep infection included the BMI (Body mass index), male gender, prolonged duration of surgery, diabetes mellitus type 2, the ASA (American society of anesthesiologists) score, the Charlson score and the NNIS (National Nosocomial Infections Surveillance System) risk index score. Female gender, age and the diagnosis of rheumatoid arthritis were not associated with deep infections. Patients with risk factors should be assessed preoperatively and receive an appropriate prophylactic antibiotic treatment, to reduce the risk of a deep infection. With the reduction of their weight and adjustment of the diabetes, patients can reduce the risk for infection by their own. Total hip replacement is still a safe and effective operation and thus should not be withheld from patients

Over 300,000 total hip arthroplasties (THA) are performed annually in the USA. Surgical Site Infections (SSI) are one of the most common complications and are associated with increased morbidity, mortality and cost. Risk factors for SSI include obesity, diabetes and smoking, but few studies have reported on the predictive value of pre-operative blood markers for SSI. The purpose of this study was to create a clinical prediction model for acute SSI (classified as either superficial, deep and overall) within 30 days of THA based on commonly ordered pre-operative lab markers and using data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. All adult patients undergoing an elective unilateral THA for osteoarthritis from 2011–2016 were identified from the NSQIP database using Current Procedural Terminology (CPT) codes. Patients with active or chronic, local or systemic infection/sepsis or disseminated cancer were excluded. Multivariate logistic regression was used to determine coefficients, with manual stepwise reduction. Receiver Operating Characteristic (ROC) curves were also graphed. The SSI prediction model included the following covariates: body mass index (BMI) and sex, comorbidities such as congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), smoking, current/previous steroid use, as well as pre-operative blood markers, albumin, alkaline phosphate, blood urea nitrogen (BUN), creatinine, hematocrit, international normalized ratio (INR), platelets, prothrombin time (PT), sodium and white blood cell (WBC) levels. Since the data met logistic assumption requirements, bootstrap estimation was used to measure internal validity. The area under the ROC curve for final derivations along with McFadden's R-squared were utilized to compare prediction models. A total of 130,619 patients were included with the median age of patients at time of THA was 67 years (mean=66.6+11.6 years) with 44.8% (n=58,757) being male. A total of 1,561 (1.20%) patients had a superficial or deep SSI (overall SSI). Of all SSI, 45.1% (n=704) had a deep SSI and 55.4% (n=865) had a superficial SSI. The incidence of SSI occurring annually decreased from 1.44% in 2011 to 1.16% in 2016. Area under the ROC curve for the SSI prediction model was 0.79 and 0.78 for deep and superficial SSI, respectively and 0.71 for overall SSI. CHF had the largest effect size (Odds Ratio(OR)=2.88, 95% Confidence Interval (95%CI): 1.56 – 5.32) for overall SSI risk. Albumin (OR=0.44, 95% CI: 0.37 – 0.52, OR=0.31, 95% CI: 0.25 – 0.39, OR=0.48, 95% CI: 0.41 – 0.58) and sodium (OR=0.95, 95% CI: 0.93 – 0.97, OR=0.94, 95% CI: 0.91 – 0.97, OR=0.95, 95% CI: 0.93 – 0.98) levels were consistently significant in all clinical prediction models for superficial, deep and overall SSI, respectively. In terms of pre-operative blood markers, hypoalbuminemia and hyponatremia are both significant risk factors for superficial, deep and overall SSI. In this large NSQIP database study, we were able to create an SSI prediction model and identify risk factors for predicting acute superficial, deep and overall SSI after THA. To our knowledge, this is the first clinical model whereby pre-operative hyponatremia (in addition to hypoalbuminemia) levels have been predictive of SSI after THA. Although the model remains without external validation, it is a vital starting point for developing a risk prediction model for SSI and can help physicians mitigate risk factors for acute SSI post THA

Total knee arthroplasty (TKA) is the most commonly performed elective orthopaedic procedure. With an increasingly aging population, the number of TKAs performed is expected to be ∼2,900 per 100,000 by 2050. Surgical Site Infections (SSI) after TKA can have significant morbidity and mortality. The purpose of this study was to construct a risk prediction model for acute SSI (classified as either superficial, deep and overall) within 30 days of a TKA based on commonly ordered pre-operative blood markers and using audited administrative data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. All adult patients undergoing an elective unilateral TKA for osteoarthritis from 2011–2016 were identified from the NSQIP database using Current Procedural Terminology (CPT) codes. Patients with active or chronic, local or systemic infection/sepsis or disseminated cancer were excluded. Multivariate logistic regression was conducted to estimate coefficients, with manual stepwise reduction to construct models. Bootstrap estimation was administered to measure internal validity. The SSI prediction model included the following co-variates: body mass index (BMI) and sex, comorbidities such as congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), smoking, current/previous steroid use, as well as pre-operative blood markers, albumin, alkaline phosphatase, blood urea nitrogen (BUN), creatinine, hematocrit, international normalized ratio (INR), platelets, prothrombin time (PT), sodium and white blood cell (WBC) levels. To compare clinical models, areas under the receiver operating characteristic (ROC) curves and McFadden's R-squared values were reported. The total number of patients undergoing TKA were 210,524 with a median age of 67 years (mean age of 66.6 + 9.6 years) and the majority being females (61.9%, N=130,314). A total of 1,674 patients (0.8%) had a SSI within 30 days of the index TKA, of which N=546 patients (33.2%) had a deep SSI and N=1,128 patients (67.4%) had a superficial SSI. The annual incidence rate of overall SSI decreased from 1.60% in 2011 to 0.68% in 2016. The final risk prediction model for SSI contained, smoking (OR=1.69, 95% CI: 1.31 – 2.18), previous/current steroid use (OR=1.66, 95% CI: 1.23 – 2.23), as well as the pre-operative lab markers, albumin (OR=0.46, 95% CI: 0.37 – 0.56), blood urea nitrogen (BUN, OR=1.01, 95% CI: 1 – 1.02), international normalized ratio (INR, OR=1.22, 95% CI:1.05 – 1.41), and sodium levels (OR=0.94, 95% CI: 0.91 – 0.98;). Area under the ROC curve for the final model of overall SSI was 0.64. Models for deep and superficial SSI had ROC areas of 0.68 and 0.63, respectively. Albumin (OR=0.46, 95% CI: 0.37 – 0.56, OR=0.33, 95% CI: 0.27 – 0.40, OR=0.75, 95% CI: 0.59 – 0.95) and sodium levels (OR=0.94, 95% CI: 0.91 – 0.98, OR=0.96, 95% CI: 0.93 – 0.99, OR=0.97, 95% CI: 0.96 – 0.99) levels were consistently significant in all prediction models for superficial, deep and overall SSI, respectively. Overall, hypoalbuminemia and hyponatremia are both significant risk factors for superficial, deep and overall SSI. To our knowledge, this is the first prediction model for acute SSI post TKA whereby hyponatremia (and hypoalbuminemia) are predictive of SSI. This prediction model can help fill an important gap for predicting risk factors for SSI after TKA and can help physicians better optimize patients prior to TKA

Aims

There is conflicting evidence on the safety of intra-articular injections of hyaluronic acid (HA) or corticosteroids (CSs) before total knee arthroplasty (TKA). We performed a meta-analysis of the relationship between intra-articular injections and subsequent infection rates after TKA.

Aim. Diagnosing Fracture-Related Infections (FRI) is challenging. White blood cell (WBC) scintigraphy is considered the best nuclear imaging technique to diagnose FRI; a recent study by our group found a diagnostic accuracy of 92%. However, many centers use . 18. F-fluorodeoxyglucose positron emission tomography/computed tomography (. 18. F-FDG-PET/CT) which has several logistic advantages. Whether . 18. F-FDG-PET/CT has better diagnostic performance than white blood cell (WBC) scintigraphy is uncertain. Therefore, we aimed: 1) to determine the diagnostic performance of . 18. F-FDG-PET/CT for diagnosing FRI (defined as infection following an open fracture or fracture surgery) and 2) to determine cut-off values of standardized uptake values (SUV) that result in optimal diagnostic performance. Method. This retrospective cohort study included all consecutive patients who received . 18. F-FDG-PET/CT to diagnose FRI in two level 1 trauma centers. Baseline demographic- and surgical characteristics were retrospectively reviewed. The reference standard consisted of at least 2 representative microbiological culture results or the presence or absence of clinical confirmatory FRI signs in at least 6 months of clinical follow-up. A nuclear medicine specialist, blinded to the reference standard, re-reviewed all scans. Additionally, SUVs were measured using the “European Association of Nuclear Medicine Research Ltd. (EARL)” reconstructed . 18. F-FDG-PET/CT scans. Volume of interests were drawn around the suspected- and corresponding contralateral area to obtain the absolute values (SUVmax) and the ratio between suspected and contralateral area (SUVratio). Diagnostic accuracy of the re-reviewed scans was calculated (sensitivity and specificity). Additionally, diagnostic characteristics of the SUV measurements were plotted in the area under the receiver operating characteristics curve (AUROC). The sensitivity and specificity at the optimal threshold was deducted from the AUROC with the Q-point method. Results. 158 . 18. F-FDG-PET/CTs were included. Mean age was 46.2 years, 71.5% was male. Most cases (56.3%) were tibial shaft- or ankle fractures. Sixty patients (38.0%) had FRI. The sensitivity and specificity of the FDG-PET/CT scan was 70.0% (95% CI 56.8–81.2) and 79.6% (95% CI 70.3–87.1) respectively. Diagnostic accuracy was 76.0% (95% CI 68.5–82.4). AUROCs of SUVmax and SUVratio were 0.80 (95% CI 0.73–0.87) and 0.73 (95% CI 0.64–0.81), respectively. The optimal SUVmax threshold of 4.2 resulted in 80.0% sensitivity and 71.3% specificity, while an SUVratio of 2.9 resulted in 58.3% sensitivity and 80.9% specificity. Conclusions. The . 18. F-FDG-PET/CT has a sensitivity of 70.0%, specificity of 79.6% and a diagnostic accuracy of 76.0%. This makes . 18. F-FDG-PET/CT less accurate than WBC scintigraphy in diagnosing FRI, although adding SUV measurements may possibly increase its diagnostic accuracy

Spinal infections are rare diseases, whose management highlights the importance of a multidisciplinary approach. Although treatment is based on antibiotics, always selected on coltural and antibiogram tests, surgery is required in case of development of spinal instability or deformity, progressive neurological deficits, drainage of abscesses, or failure of medical treatment. The first step of the algorithm is diagnosis, that is established on MRI with contrast, PET/CT scan, blood tests (CRP and ESR) and CT-guided needle biopsy. Evaluation of response to the specific antibiotic therapy is based on variations in Maximum Standardized Uptake Value (SUVmax) after 2 to 4 weeks of treatment. In selected cases, early minimally invasive surgery was proposed to provide immediate stability and avoid bed-rest. From 1997 to 2014, 182 patients affected by spinal infections have been treated at the same Institution (Istituto Ortopedico Rizzoli – Bologna, Italy) according to the proposed algorithm. Mean age was 56 years (range 1 – 88). Male to female ratio was 1.46. Minimum follow-up was 1 year. Infections were mostly located in the lumbar spine (57%) followed by thoracic (37%) and cervical spine (6%). Conservative treatment based on antibiotics needed surgery (open and/or percuteneous minimally invasive) as an adjuvant in 83 patients out of 182 (46%). Management of spinal infections still remains a challenge in spinal surgery and a multisciplinary approach is mandatory. This algorithm represents the shared decision- making process from diagnosis to the most appropriate treatment and it led to successful outcomes with a low-complication rate. We present this algorithm developed to organize the various professionals involved (orthopaedic surgeons, nuclear medicine and infective disease specialists, interventional radiologists and anaestesiologists) and set a shared pathway of decision making in order to uniform the management of this complex disease

There is currently no consensus on the use of suppressive antibiotic therapy (SAT) in prosthetic joint infections (PJI) (1). We describe herein the experience of a French Reference Centre for Complex Osteo-Articular Infections on use of oral cyclines (doxycline and minocycline) for SAT. A retrospective analysis was performed on consecutive patients with PJI who received oral cyclines (doxycycline or minocycline) for SAT between January 2006 and June 2014. All patients had surgical management, followed by systemic antibiotic treatment and SAT instauration thereafter. Remission was defined as an asymptomatic patient with a functioning prosthesis. Seventy-nine patients with a mean age of 63.8 ± 16.8 years were included. Sixteen patients (20%) had neoplasia, 9 (11%) diabetes mellitus, 10 (13%) rheumatoid arthritis, and 6 patients (8%) were receiving corticosteroids or chemotherapy. There were 37 knee (47%), 36 hip (46%), 4 elbow (5%), and 2 shoulder (3%) infections, with a mean delay from implantation of 7.37 ± 6.94 months (range 1–27). Surgical management consisted in debridement and implant retention for 60 patients (76%), or in implant exchange for 19 patients (24%). Main pathogens were coagulase-negative staphylococci (37%) and Staphylococcus aureus (41%); 23 patients had polymicrobial infection (29%). The most frequent initial antibiotic regimens debuted before SAT were rifampicin combinations (70%). Mean duration of curative antibiotic therapy was 103 ± 75 days. Indications of SAT were (i) patients unsuitable for or refusing further surgery (n=23), suboptimal (ii) surgery (n=26) or (iii) curative antibiotic therapy (n=11), (iv) complex orthopaedic surgery (n=11), and (v) immunosuppressive status (n=8). Seventy-three patients received doxycycline and 6 patients received minocycline as SAT (n=48). Mean SAT duration was 625± 536 days (range 30–2900), with a mean follow-up of 765 ± 572 days. Adverse events were reported in 13 patients (16%), leading to SAT discontinuation in 5 (6%). During follow-up, 59 patients were considered in remission (75%), and 20 failed including 13 relapses (16%) and 7 reinfections (9%). Among failure patients, 10 pathogens resistant to doxy/minocycline were identified, including 5 with acquisition of cycline resistance. In our study, SAT with cyclines is associated to a 75% remission rate, with an acceptable tolerability. Further studies are warranted to determine ideal regimens and optimal duration of SAT. We would like to thank Dron Hospital and Lille University Hospital medical teams. The authors declare that there are no conflicts of interest

Aim. Data of optimal management of infections after internal fixation (IIF) is scarce and long-term follow-up results often lack. We analyzed characteristics of infections after intramedullary (IIIF) and extramedullary long bone fixation (IEIF) and evaluated their infection and functional outcome. Method. Consecutive patients with IIF diagnosed at our institution from 01/2010-10/2017 were retrospectively included. Infection was defined as visible purulence, sinus tract, microbial growth in ≥2 independent samples or positive histopathology. The outcome was compared before and after implementation of a comprehensive surgical and antimicrobial treatment algorithm in 04/2013. Results. Of 127 patients, infection involved lower extremity in 111 patients (87%). Median age was 53 years (range, 19–89 years), 70% were men. Fixation was performed with intramedullary nail in 47 (37%) and with extramedullary osteosynthesis (plates, screws, pins) in 80 patients (63%). At infection diagnosis, the implant was in situ in 96 patients (76%), whereas 31 patients (24%) had residual osteomyelitis after implant removal. The time from bone fixation to infection was longer in IIIF than IEIF (25 vs. 7 months, p=0.027). Pain was reported in 55 patients (43%) and local infection signs in 96 patients (75%), including sinus tract in 46 patients, more commonly reported after IIIF than IEIF (49% vs. 29%, p=0.035). Infections were monomicrobial in 85 (67%), polymicrobial in 18 (14%) and culture-negative in 23 patients (18%). Most common pathogens were S. aureus (43%), coagulase-negative staphylococci (28%) and gram-negative rods (22%). Débridement (with device retention, if present) was performed in 40, device removal in 43, one-stage exchange in 16 and two-stage exchange in 20 patients. One patient had no surgery and 7 patients underwent limb amputation. 43 patients (34%) were treated before implementation of the interdisciplinary treatment concept and 84 patients (66%) afterwards. Among 111 patients with available follow-up (median, 5.2 months; range, 0.2–86 months), in 78 cases (70%) infection eradication was achieved (similar in IIIF and IEIF). However, overall infection and functional outcome was only 48% (53 patients). After implementation of the treatment algorithm, the infection outcome improved from 56% to 79% (p=0.03) and the overall success from 33% to 56% (p=0.016). Conclusions. Approximately half of infections after IIF failed in terms of infection eradication or restoration of function. After implementation of standardized surgical and antibiotic treatment concept, infection and functional outcome improved significantly. No significant differences between IIIF and IEIF was observed in terms of infection and functional success

Aim

Treatment recommendations for periprosthetic joint infections (PJI) include surgical debridement, antibiotic therapy or staged revision. In surgical related foot and ankle infections (SR-FAI), implant removal will lead to instability. Debridement is difficult because the implant is outside the joint. Recommendations regarding PJI treatment can therefore not be extrapolated to the treatment of SR-FAI.

Staphylococcus aureus (SA), the predominant pathogen in human osteomyelitis, is known to persist by forming intracellular reservoirs, including in bone cells (Schwarz et al., 2019, Yang et al., 2018, Krauss et al., 2019, Gao et al., 2020, Bosse et al., 2005), promoting decreased antibiotic susceptibility. However, there are no evidence-based treatment guidelines for intracellular SA infections in osteomyelitis. We sought to address this by systematically reviewing the literature and, testing a selection of antibiotic treatments in a clinically relevant in vitro assay.

We conducted a systematic review of the literature to determine the current evidence for the efficacy of antibiotics against intracellular SA infections relevant to osteomyelitis. For the antibiotics identified as potentially useful, we determined their minimal inhibitory concentration (MIC) against 11 clinical osteomyelitis SA- isolates. We selected those for further testing reported able to reach a higher concentration in the bone than the identified MIC against the majority of strains. Thus, rifampicin, oxacillin, linezolid, levofloxacin, oritavancin and doxycycline were tested in human SaOS-2-osteocyte infection models (Gunn et al., 2021) of acute (1d) or chronic (14d) infection to clear intracellular SA. Antibiotics were tested at 1x/4x/10x the MIC for the duration of 1d or 7d in each model.

A systematic review found that osteoblasts and macrophages have mostly been used to test immediate short-term activity against intracellular SA, with a high variability in methodology. However, some extant evidence supports that rifampicin, oritravancin, linezolid, moxifloxacin and oxacillin may be effective intracellular treatments. While studies are ongoing, in vitro testing in a clinically relevant model suggests that rifampicin, oxacillin and doxycycline could be effectively used to treat osteomyelitic intracellular SA infections. Importantly, these have lower MICs against multiple clinical isolates than their respective clinically-achievable bone concentrations.

The combined approach of a systematic review and disease-relevant in vitro screening will potentially inform as to the best approach for treating osteomyelitis where intracellular SA infection is confirmed or suspected.