Aims. Achievement of accurate microbiological diagnosis prior to revision is key to reducing the high rates of persistent infection after revision knee surgery. The effect of change in the microorganism between the first- and second-stage revision of total knee arthroplasty for periprosthetic joint infection (PJI) on the success of management is not clear. Methods. A two-centre retrospective cohort study was conducted to review the outcome of patients who have undergone two-stage revision for treatment of knee arthroplasty PJI, focusing specifically on isolated micro-organisms at both the first- and second-stage procedure. Patient demographics, medical, and orthopaedic history data, including postoperative outcomes and subsequent treatment, were obtained from the electronic records and medical notes. Results. The study cohort consisted of 84 patients, of whom 59.5% (n = 50) had successful eradication of their infection at a mean follow-up of 4.7 years. For the 34 patients who had recurrence of infection, 58.8% (n = 20) had a change in isolated organism, compared to 18% (n = 9) in the infection eradication group (p < 0.001). When adjusting for confound, there was no association when the growth on the second stage was the same as the first (odd ratio (OR) 2.50, 95% confidence interval (CI) 0.49 to 12.50; p = 0.269); however, when a different organism was identified at the second stage, this was independently associated with failure of treatment (OR 8.40, 95% CI 2.91 to 24.39; p < 0.001). There were no other significant differences between the two cohorts with regard to patient demographics or type of organisms isolated. Conclusion. Change in the identified microorganism between first- and second-stage revision for PJI was associated with failure of management. Identification of this change in the microorganism prior to commencement of the second stage may help target antibiotic management and could improve the success of surgery in these patients. Cite this article: Bone Jt Open 2023;4(9):720–727

Aims

Gram-negative periprosthetic joint infection (PJI) has been poorly studied despite its rapidly increasing incidence. Treatment with one-stage revision using intra-articular (IA) infusion of antibiotics may offer a reasonable alternative with a distinct advantage of providing a means of delivering the drug in high concentrations. Carbapenems are regarded as the last line of defense against severe Gram-negative or polymicrobial infection. This study presents the results of one-stage revision using intra-articular carbapenem infusion for treating Gram-negative PJI, and analyzes the characteristics of bacteria distribution and drug sensitivity.

Aim. It is unclear if the prevalence of resistance organisms causing (PJI) in total hip/knee arthroplasty is different among North/South American and European countries. Therefore, we sought to compare causative organisms, rates of resistant organisms, and polymicrobial infections in hospitals in North/South America, and Europe. Method. We performed a retrospective study of 654 periprosthetic hip (n=361) and knee (n=293) infections (January 2006-October 2019) identified at two facilities in the United States (US) (n=159), and single institutions located in Argentina (n=99), Uruguay (n=130), United Kingdom (UK) (n=103), Germany (n=59), and Russia (n=104). The analyses were performed for the entire cohort, knees, and hips. Alpha was set at 0.05. Results. Overall, the most frequent organisms identified were Staphylococcus aureus (24.8%) and Staphylococcus epidermidis (21.7%). The incidence of organisms resistant to at least one antibiotic was 58%. In this regard, there was a significant difference between hips (62.3%) and knees (52.6%) (p=0.014). The rates of resistant organisms among countries were significantly different: 37.7% (US), 66.7% (Argentina), 71.5% (Uruguay), 40.8% (UK), 62.7% (Germany), and 77.9% (Russia) (p<0.001). The overall incidence of polymicrobial infections was 9.3% and the rates across nations were: 9.4% in the US, 11.1% (Argentina), 4.6% (Uruguay), 4.9% (UK), 11.9% (Germany), and 16.3% (Russia) (p=0.026). In an exclusive analysis of the hips, the incidence of resistant organisms was 62.3% while polymicrobial infections accounted for 10.5% of all cultures. The rates of resistant organisms in each country were: 42.9% in the US, 59.2% (Argentina), 78.5% (Uruguay), 41.3% (UK), 63.9% (Germany), and 80.0% in Russia (p<0.001). The incidences of polymicrobial infections were: 9.1% in the US, 6.1% (Argentina), 6.5% (Uruguay), 6.5% (UK), 16.7% (Germany), and 21.7% in Russia (p=0.024). Regarding the knees, the incidence of resistant organisms was 52.6% while the frequency of polymicrobial infections was 7.8%. The rates of resistant organisms in each country were: 32.9% in the US, 74% (Argentina), 54.1% (Uruguay), 40.4% (UK), 60.9% (Germany), and 75% in Russia (p<0.001). The frequencies of polymicrobial infections were: 9.8% in the US, 16% (Argentina), 0% (Uruguay), 3.5% (UK), 4.3% (Germany), and 9.1% in Russia (p=0.072). Conclusions. Staphylococcus aureus and epidermidis accounted for almost 50% of all infections. The US and the UK had the lowest incidence of resistant organisms while Germany and Russia had the highest. The UK and Uruguay had the lowest rates of polymicrobial infections. These differences between countries and continents may affect comparative studies that evaluate treatments for PJI

Aim. It is traditionally stated that around 80% of all periprosthetic joint infections (PJI) are caused by well-known gram-positive organisms such as Staphylococcus aureus. With the advances in diagnostic modalities and improved abilities to isolate infective organisms, we believe the organism profile causing PJI has changed over time and includes numerous other organisms that were either not recognized as pathogens and/or considered as contaminants. Method. We retrospectively reviewed the medical records of 1,363 patients with confirmed PJI (559 THA and 804 TKA) who received treatment at our institution between 2000 and 2019. Pertinent data related to demographics, microbiological findings, and outcome of treatment were collected. Organisms were differentiated using culture or confirmed by Matrix-Assisted Laser Desorption Ionization-time of flight (MALDI-tof) mass spectrometry. Statistical analysis included logistic regressions. Results. There was a total of 26 different species of organisms that resulted in PJI in our cohort. The rate of PJI caused by slow growing organisms, that are catalase negative, such as Streptococcal viridans (OR 1.244; 95% CI 1.036–1.494), Streptococcus agalactiae (OR 1.513; 95% CI 1.207–1.898), and Staphylococcus epidermidis (OR 1.321; 95% CI 1.191–1.466) has been increasing over time. In contrast, the incidence of PJI caused by coagulase-negative Staphylococcus (OR 0.954; 95% CI 0.927–0.981); resistant species (OR 0.962, 95% CI 0.931–0.995), and Gram-positive species (OR 0.94, 95% CI 0.914–0.966) decreased over time. Notably, there was a higher prevalence of Streptococcal PJI (OR 0.551, 95% CI 0.374–0.812) and culture-negative PJI (OR 0.652, 95% CI 0.478–0.890) seen in knees versus hips. The rate of culture negative PJI also increased from 20% in 2000 to 28% in 2019. In the latter years of the study, very unusual list of organisms causing PJI were also identified. Conclusions. This study reveals that the list of organisms causing PJI has expanded in recent years. The study also finds that some the slow growing organisms that were previously believed to be “contaminants” can and do cause PJI in a considerable number of patients. The number of culture negative cases of PJI has also increased at our institution over the years. There are a number of explanations for the latter finding, perhaps with the most important reason being liberal use of antibiotics that interferes with isolation of the infective organism

Abstract. Introduction. The prevalence of recurrent infection following two-stage exchange arthroplasty following failure of a total knee arthroplasty (TKA) has been reported to be 10% to 25%. There is limited literature available on repeat two stage revisions for TKA infection with only small cohorts and variable success rates. Methodology. A retrospective cohort study investigating the outcome of two stage revision arthroplasty for treatment of TKA infection was conducted with the aim of identifying factors linked to recurrence of infection. A consecutive cohort of all microbiology intra-operative periprosthetic knee samples from a single revision arthroplasty centre between January 2010 and December 2016 was identified. The final cohort consisted of 658 samples taken during 64 patients undergoing two stage revision knee surgery for infection. Patient demographics, medical and orthopaedic history data including post-operative outcomes and subsequent treatment was obtained from the electronic records system and medical notes. Results. 65.6% of the cohort (N=42) had successful eradication of their infection. For the twenty-two patients that had failure of their two stage revision, twenty patients had samples available from further surgical intervention. Sixteen patients (80%) had different organisms isolated when they had repeat surgical samples taken when compared to their first stage samples. Overall, for subsequent treatments there was a success rate of 75% if the same organism was identified and 62.5% if there were new isolated organisms. Conclusion. These findings may have implications for the treatment strategies chosen for re-infection after two stage TKA revisions if new causative organisms are isolated

Aim. To determine mortality and outcomes of patients diagnosed with fracture-related infections (FRIs). Method. FRI patients treated at a trauma centre between 2001 and 2020 were analysed. The primary outcome was 1-year mortality; mortality associations with FRI organism, depth of involvement, and temporality were investigated with multivariable survival analysis. Healthcare-associated and serological outcomes were reported as secondary outcomes. Results. 311 FRIs with mean age of 67.0 and median Charlson comorbidity index of 0 were analysed. Methicillin-sensitive Staphylococcus aureus (MSSA) (29.9%) was the most frequently implicated organism. The majority of FRIs were deep infections (62.7%). FRIs were diagnosed at a median of 40 (IQR 15–200) days post index surgery. The mean follow-up was 5.9 years. One-year mortality amounted to 17.7%. MSSA FRIs were associated with better survival (adj HR 0.34, 95%CI 0.15–0.76, p=0.008). There was no difference in survivorship between deep or superficial FRI (adj HR 0.86, 95%CI 0.62–1.19, p=0.353) or in relation to onset time (adj HR 1.0, 95%CI 0.99–1.00, p=0.943). Implant removal or debridement alone was performed in 61.7% and 17% respectively. Antibiotics was prescribed for 53 (IQR 23–110) days, and patients were hospitalised for 39 (IQR 19–78) days. CRP and ESR normalised in 70.3% (median 46 days) and 53.8% (median 86 days) patients respectively. Conclusions. Fracture-related infections are associated with significant mortality and morbidity regardless of depth and temporality. Non-MSSA FRIs are associated with inferior survival

Aims. The aim of this study was to determine the prevalence and characteristics of C-reactive protein (CRP)-negative prosthetic joint infection (PJI) and evaluate the influence of the type of infecting organism on the CRP level. Patients and Methods. A retrospective analysis of all PJIs affecting the hip or knee that were diagnosed in our institution between March 2013 and December 2016 was performed. A total of 215 patients were included. Their mean age was 71 years (. sd. 11) and there were 118 women (55%). The median serum CRP levels were calculated for various species of organism and for patients with acute postoperative, acute haematogenous, and chronic infections. These were compared using the Kruskal–Wallis test, adjusting for multiple comparisons with Dunn’s test. The correlation between the number of positive cultures and serum CRP levels was estimated using Spearman correlation coefficient. Results. Preoperative CRP levels were normal (< 10 mg/l) in 77 patients (35.8%) with positive cultures. Low-virulent organisms were isolated in 66 PJIs (85.7%) with normal CRP levels. When grouping organisms by species, patients with an infection caused by Propionibacterium spp., coagulase-negative staphylococci (CNS), and Enterococcus faecalis had significantly lower median serum CRP levels (5.4 mg/l, 12.2 mg/l, and 23.7 mg/l, respectively), compared with those with infections caused by Staphylococcus aureus and Streptococcus spp. (194 mg/l and 89.3 mg/l, respectively; p < 0.001). Those with a chronic PJI had statistically lower median serum CRP levels (10.6 mg/l) than those with acute postoperative and acute haematogenous infections (83.7 mg/l and 149.4 mg/l, respectively; p < 0.001). There was a significant correlation between the number of positive cultures and serum CRP levels (Spearman correlation coefficient, 0.456; p < 0.001). Conclusion. The CRP level alone is not accurate as a screening tool for PJI and may yield high false-negative rates, especially if the causative organism has low virulence. Aspiration of the joint should be used for the diagnosis of PJI in patients with a chronic painful arthroplasty, irrespective of CRP level. Cite this article: Bone Joint J 2018;100-B:1482–86

The aim of our study is to identify the organisms causing delayed deep infections following primary total knee arthroplasty in the current situation. We also compared the differences in outcome based on the infecting organism. We undertook a retrospective study of all the patients who presented with delayed deep infection following primary total knee replacement during a six year period between April 1998 and March 2004. We analysed the infecting organism, sensitivity of the organism to antibiotics, number of surgical procedure carried out and the outcome of the infected arthroplasty based on the infecting organism. Statistical analysis was done using Fisher’s Exact test for categorical data and Mann-Whitney U test for the non-parametric numeric data. The mean age at the time of primary arthroplasty was 69.9 years (range 46 to 92 years, SD=10.8). The mean follow-up (time since the initial knee replacement) was 77.3 months (range 27–170 months,). The mean follow-up since the last surgical procedure to treat infection was 31 months (range 14–47 months). Organisms were isolated in 27 of the 31 patients who presented with delayed deep infection. Forty-four % of the organisms isolated were multi-drug resistant with increasing incidence of Methicillin resistant Staphylococcus aureus and multi-drug resistant Staphylococcus epidermidis infections. Successful outcome following an infected total knee arthroplasty was lower compared to the previous studies where there were fewer multi-drug resistant organisms. The number of patients with satisfactory outcome is significantly lower when the organism isolated is multi-drug resistant. Patients infected by multi-drug resistant organisms undergo higher number of surgical procedures compared to patients where the organism is not multi-drug resistant. We conclude that deep infection with MRSA and Methicillin resistant Staphylococcus epidermidis are on the rise. Outcome is significantly better when the organism isolated is non resistant Staphylococcus aureus

Infection following total knee arthroplasty is a serious complication. Recently there has been increasing incidence of isolation of multi-drug resistant bacteria from peri-prosthetic infections. The aim of our study is to identify the organisms causing delayed deep infections following primary total knee arthroplasty in the current situation. We also compared the differences in outcome based on the infecting organism. We undertook a retrospective study of all the patients who presented with delayed deep infection following primary total knee replacement during a six year period between April 1998 and March 2004. Organisms were isolated in 27 of the 31 patients who presented with delayed deep infection. Forty-four % of the organisms isolated were multi-drug resistant with increasing incidence of Methicillin resistant Staphylococcus aureus and multi-drug resistant Staphylococcus epidermidis infections. Successful outcome following an infected total knee arthroplasty was lower compared to the previous studies where there were fewer multi-drug resistant organisms. The average number of surgical procedures carried out was significantly higher when the organism isolated was multi-drug resistant. The number of patients with satisfactory outcome is significantly lower when the organism isolated is multi-drug resistant

Perioperative antibiotic prophylaxis remains one of the most important strategies for prevention of periprosthetic joint infection (PJI) with current guideline recommending a first or second generation cephalosporin. Penicillin (PCN) allergy is often reported by patients, which often results in avoidance of administration of cephalosporins due to fear of cross-reactivity. Alternative medications, such as vancomyin, are often used despite reduced antimicrobial coverage. The purpose of this study was to determine if PCN allergic patients who received vancomycin alone prior to elective primary total joint arthroplasty were at increased risk of developing a subsequent PJI. A retrospective review of 7,602 primary total joint arthroplasties (TJAs) performed between 2005 and 2013 in two institutions were identified using a prospective institutional database. Patient reported PCN or cephalosporin allergy was electronically queried from the anesthesia note. Patients who recieved multiple prophylactic antibiotics, or had unavailable perioperative antibiotic information, or those who received medication other than cefazolin and vancomycin were excluded. PJI was determined using a cross-match with an institutional PJI database constructed from International Classification of Diseases (ICD)-9 codes. Logistic regression analysis was then performed to evaluate the risk of subsequent PJI. The rate of PJI was 1.4% (32/2296) in patients with a reported PCN allergy that received vancomycin alone versus 1.1% (59/5306) in non-PCN allergic patients that received cefazolin alone. The multivariate analysis, with the given sample size, did not detect a statistically significant increased risk of PJI when vancomycin was administered alone (adjusted odds ratio: 1.23, 95% CI 0.6–3.1, p=0.35). While there was no significant differences in the organism profile between PJIs in both groups, the rate of PJI caused by resistant organisms was higher in patients who received vancomycin alone (11.9%, 7/59) compared to those who received cefazolin (3.1%, 1/32). While administration of perioperative prophylactic vancomycin alone during elective primary arthroplasty does not seem to result in a higher rate of subsequent PJI, patients who received vancomycin alone and developed a PJI were more likely to develop an infection with an antibiotic resistant organism. Future studies are needed to determine the most appropriate prophylactic antibiotic for patients who undergo elective arthroplasty and report PCN allergy

Introduction: Osteomyelitis remains a rare diagnosis and a difficult one to make. Acute osteomyelitis in the context of sickle cell disease remains the subject of some controversy, particularly with regard to aetiology. It is known that Salmonella species are more commonly the cause of acute bone infection in sickle cell patients than in patients with normal red blood cell morphology, but there has long been an argument as to whether Staphylococcus Aureus is in fact still the most common bacterial cause overall in this patient group, as it is in the population overall. We present a consecutive case series of 12 cases of acute osteomyelitis in paediatric patients in East London over the last twenty years. Materials and Methods: Retrospective review of 12 consecutive cases. Medical Notes along with microbiology records and radiographic results were cross referenced with a paediatric sickle cell data base held by the haematology department. Results: 10 of the 12cases had an organism isolated from either blood or bone culture(s). Salmonella spp in cases, S. Aureus in 2 cases and Pseudomonas in the remaining case. Discussion: The question of causative organism is complicated by the fact that most case series’ have bracketed adults and children together, and that conflicting conclusions have resulted from quite small, usually retrospective studies at different times and from different parts of the world – Nigeria, Saudi Arabia and the United States of America. It appears that endemicity is a result of many factors including age; race and socioeconomic factors all play a role. Conclusion: These results reveal that in our paediatric sickle cell population, Salmonella infection occurs ore commonly than Staphylococcus

Aims. Gram-negative infections are associated with comorbid patients, but outcomes are less well understood. This study reviewed diagnosis, management, and treatment for a cohort treated in a tertiary spinal centre. Methods. A retrospective review was performed of all gram-negative spinal infections (n = 32; median age 71 years; interquartile range 60 to 78), excluding surgical site infections, at a single centre between 2015 to 2020 with two- to six-year follow-up. Information regarding organism identification, antibiotic regime, and treatment outcomes (including clinical, radiological, and biochemical) were collected from clinical notes. Results. All patients had comorbidities and/or non-spinal procedures within the previous year. Most infections affected lumbar segments (20/32), with Escherichia coli the commonest organism (17/32). Causative organisms were identified by blood culture (23/32), biopsy/aspiration (7/32), or intraoperative samples (2/32). There were 56 different antibiotic regimes, with oral (PO) ciprofloxacin being the most prevalent (13/56; 17.6%). Multilevel, contiguous infections were common (8/32; 25%), usually resulting in bone destruction and collapse. Epidural collections were seen in 13/32 (40.6%). In total, five patients required surgery, three for neurological deterioration. Overall, 24 patients improved or recovered with a mean halving of CRP at 8.5 days (SD 6). At the time of review (two to six years post-diagnosis), 16 patients (50%) were deceased. Conclusion. This is the largest published cohort of gram-negative spinal infections. In older patients with comorbidities and/or previous interventions in the last year, a high level of suspicion must be given to gram-negative infection with blood cultures and biopsy essential. Early organism identification permits targeted treatment and good initial clinical outcomes; however, mortality is 50% in this cohort at a mean of 4.2 years (2 to 6) after diagnosis. Cite this article: Bone Jt Open 2024;5(5):435–443

Objective. Pyogenic spinal infection (PSI) is an increasingly common presentation to spinal units in the UK. Its investigation and diagnosis is often delayed. The purpose of this study was to determine the prognostic significance of the inflammatory marker levels on admission on achieving a positive microbiological diagnosis in patients with PSI. Study design. Retrospective case series review of all patients presenting with PSI to our unit. Subjects. Clinical data were collected on 96 consecutive patients diagnosed with a PSI over a 7-year period. Patient < 18 years at time of presentation or who had previous spinal surgery were excluded. Outcome Measures. Positive blood and/or tissue culture, and requirement for surgery. Continuous data were compared using the Wilcoxon rank-sum test∗∗ and logistical regression remodelling was assessed using the Spearman correlation∗. Categorical data was analysed using Fisher's exact test. ∗∗∗. Results. The C-reactive protein was statistically significant for; duration of preceding symptoms (p=0.0003)∗, isolation of a causative organism (p< 0.0001)∗∗, positive biopsy culture (p=0.0016)∗∗ and requirement for surgery (p=0.031)∗∗. The White Blood Cell (WBC) count was statistically significant for; duration of preceding symptoms (p< 0.0001)∗, isolation of a causative organism (p = 0.0003)∗∗, positive biopsy culture (p=0.0023)∗∗. The majority of patients who had a positive tissue culture had a positive blood culture (p< 0.0001)∗∗∗. Conclusion. The inflammatory marker levels on admission are a useful prognostic marker for isolating a causative organism in patients with PSI and help guide treating surgeons to whether proceeding to biopsy is likely to be a helpful investigation. Tissue biopsy in patients with PSI is only marginally superior to blood culture alone

Aims. Excision of chronic osteomyelitic bone creates a dead space which must be managed to avoid early recurrence of infection. Systemic antibiotics cannot penetrate this space in high concentrations, so local treatment has become an attractive adjunct to surgery. The aim of this study was to present the mid- to long-term results of local treatment with gentamicin in a bioabsorbable ceramic carrier. Methods. A prospective series of 100 patients with Cierny-Mader Types III and IV chronic ostemyelitis, affecting 105 bones, were treated with a single-stage procedure including debridement, deep tissue sampling, local and systemic antibiotics, stabilization, and immediate skin closure. Chronic osteomyelitis was confirmed using strict diagnostic criteria. The mean follow-up was 6.05 years (4.2 to 8.4). Results. At final follow-up, six patients (six bones) had recurrent infection; thus 94% were infection-free. Three infections recurred in the first year, two in the second year, and one 4.5 years postoperatively. Recurrence was not significantly related to the physiological class of the patient (1/20 Class A (5%) vs 5/80 Class B (6.25%); p = 0.833), nor was it significantly related to the aetiology of the infection, the organisms which were cultured or the presence of nonunion before surgery (1/10 with nonunion (10%) vs 5/90 without nonunion (5.6%); p = 0.570). Organisms with intermediate or high-grade resistance to gentamicin were significantly more likely in polymicrobial infections (9/21; 42.8%) compared with monobacterial osteomyelitis (7/79 (8.9%); p < 0.001). However, recurrence was not significantly more frequent when a resistant organism was present (1/16 for resistant cases (6.25%) vs 5/84 in those with a microbiologically sensitive infection (5.95%); p = 0.958). Conclusion. We found that a single-stage protocol, including the use of a high-delivery local antibiotic ceramic carrier, was effective over a period of several years. The method can be used in a wide range of patients, including those with significant comorbidities and an infected nonunion. Cite this article: Bone Joint J 2022;104-B(9):1095–1100

Aims. Deep surgical site infection (SSI) remains an unsolved problem after hip fracture. Debridement, antibiotic, and implant retention (DAIR) has become a mainstream treatment in elective periprosthetic joint infection; however, evidence for DAIR after infected hip hemiarthroplaty is limited. Methods. Patients who underwent a hemiarthroplasty between March 2007 and August 2018 were reviewed. Multivariable binary logistic regression was performed to identify and adjust for risk factors for SSI, and to identify factors predicting a successful DAIR at one year. Results. A total of 3,966 patients were identified. The overall rate of SSI was 1.7% (51 patients (1.3%) with deep SSI, and 18 (0.45%) with superficial SSI). In all, 50 patients underwent revision surgery for infection (43 with DAIR, and seven with excision arthroplasty). After adjustment for other variables, only concurrent urinary tract infection (odds ratio (OR) 2.78, 95% confidence interval (CI) 1.57 to 4.92; p < 0.001) and increasing delay to theatre for treatment of the fracture (OR 1.31 per day, 95% CI 1.12 to 1.52; p < 0.001) were predictors of developing a SSI, while a cemented arthroplasty was protective (OR 0.54, 95% CI 0.31 to 0.96; p = 0.031). In all, nine patients (20.9%) were alive at one year with a functioning hemiarthroplasty following DAIR, 20 (46.5%) required multiple surgical debridements after an initial DAIR, and 18 were converted to an excision arthroplasty due to persistent infection, with six were alive at one year. The culture of any gram-negative organism reduced success rates to 12.5% (no cases were successful with methicillin-resistant Staphylococcus aureus or Pseudomonas infection). Favourable organisms included Citrobacter and Proteus (100% cure rate). The all-cause mortality at one year after deep SSI was 55.87% versus 24.9% without deep infection. Conclusion. Deep infection remains a devastating complication regardless of the treatment strategy employed. Success rates of DAIR are poor compared to total hip arthroplasty, and should be reserved for favourable organisms in patients able to tolerate multiple surgical procedures. Cite this article: Bone Jt Open 2021;2(11):958–965

Prophylactic antibiotics are important in reducing the risk of periprosthetic joint infection (PJI) following total knee arthroplasty. Their effectiveness depends on the choice of antibiotic and the optimum timing of their administration, to ensure adequate tissue concentrations. Cephalosporins are typically used, but an increasing number of resistant organisms are causing PJI, leading to the additional use of vancomycin. There are difficulties, however, with the systemic administration of vancomycin including its optimal timing, due to the need for prolonged administration, and potential adverse reactions. Intraosseous regional administration distal to a tourniquet is an alternative and attractive mode of delivery due to the ease of obtaining intraosseous access. Many authors have reported the effectiveness of intraosseous prophylaxis in achieving higher concentrations of antibiotic in the tissues compared with intravenous administration, providing equal or enhanced prophylaxis while minimizing adverse effects. This annotation describes the technique of intraosseous administration of antibiotics and summarizes the relevant clinical literature to date. Cite this article: Bone Joint J 2023;105-B(11):1135–1139

Aims. Musculoskeletal infection is a devastating complication in both trauma and elective orthopaedic surgeries that can result in significant morbidity. Aim of this study was to assess the effectiveness and complications of local antibiotic impregnated dissolvable synthetic calcium sulphate beads (Stimulan Rapid Cure) in the hands of different surgeons from multiple centres in surgically managed bone and joint infections. Methods. Between January 2019 and December 2022, 106 patients with bone and joint infections were treated by five surgeons in five hospitals. Surgical debridement and calcium sulphate bead insertion was performed for local elution of antibiotics in high concentration. In all, 100 patients were available for follow-up at regular intervals. Choice of antibiotic was tailor made for each patient in consultation with microbiologist based on the organism grown on culture and the sensitivity. In majority of our cases, we used a combination of vancomycin and culture sensitive heat stable antibiotic after a thorough debridement of the site. Primary wound closure was achieved in 99 patients and a split skin graft closure was done in one patient. Mean follow-up was 20 months (12 to 30). Results. Overall, six out of 106 patients (5.6%) presented with sepsis and poorly controlled comorbid conditions, and died in the hospital within few days of index surgery. Out of the remaining 100 patients, control of infection was achieved in 95 patients (95%). Persistence of infection was noted in five (5%) patients. Out of these 95 patients that had good control of infection, four patients (4.2%) with gap nonunion needed Masquelet procedure to achieve union. Conclusion. Our multicentre experience confirmed that surgical debridement along with calcium sulphate bead insertion was effective in treating bone and joint infections without any side effects and complications. Cite this article: Bone Jt Open 2023;4(7):516–522

Aims. The number of revision arthroplasties being performed in the elderly is expected to rise, including revision for infection. The primary aim of this study was to measure the treatment success rate for octogenarians undergoing revision total hip arthroplasty (THA) for periprosthetic joint infection (PJI) compared to a younger cohort. Secondary outcomes were complications and mortality. Methods. Patients undergoing one- or two-stage revision of a primary THA for PJI between January 2008 and January 2021 were identified. Age, sex, BMI, American Society of Anesthesiologists grade, Charlson Comorbidity Index (CCI), McPherson systemic host grade, and causative organism were collated for all patients. PJI was classified as ‘confirmed’, ‘likely’, or ‘unlikely’ according to the 2021 European Bone and Joint Infection Society criteria. Primary outcomes were complications, reoperation, re-revision, and successful treatment of PJI. A total of 37 patients aged 80 years or older and 120 patients aged under 80 years were identified. The octogenarian group had a significantly lower BMI and significantly higher CCI and McPherson systemic host grades compared to the younger cohort. Results. The majority of patients were planned to undergo two-stage revision, although a significantly higher proportion of the octogenarians did not proceed with the second stage (38.7% (n = 12) vs 14.8% (n = 16); p = 0.003). Although there was some evidence of a lower complication rate in the younger cohort, this did not reach statistical significance (p = 0.065). No significant difference in reoperation (21.6% (n = 8) vs 25.0% (n = 30); p = 0.675) or re-revision rate (8.1% (n = 3) vs 16.7% (n = 20); p = 0.288) was identified between the groups. There was no difference in treatment success between groups (octogenarian 89.2% (n = 33) vs control 82.5% (n = 99); p = 0.444). Conclusion. When compared to a younger cohort, octogenarians did not show a significant difference in complication, re-revision, or treatment success rates. However, given they are less likely to be eligible to proceed with second stage revision, consideration should be given to either single-stage revision or use of an articulated spacer to maximize functional outcomes. Cite this article: Bone Joint J 2024;106-B(8):802–807

Aims. Debridement, antibiotics, and implant retention (DAIR) is a widely accepted form of surgical treatment for patients with an early periprosthetic joint infection (PJI) after primary arthroplasty. The outcome of DAIR after revision arthroplasty, however, has not been reported. The aim of this study was to report the success rate of DAIR after revision arthroplasty with a follow-up of two years. Methods. This retrospective study, conducted at the Sint Maartenskliniek, Nijmegen, the Netherlands, included 88 patients who underwent DAIR within 90 days of revision total hip or total knee arthroplasty between 2012 and 2019. Details of the surgical procedures and PJI were collected. Univariate analysis and a subgroup analysis of the culture-positive group were performed. Kaplan-Meier survivorship curves were constructed. Results. The overall success rate of DAIR, with respect to the retention of components and the cure of infection, was 68% after two years. DAIR performed with an interval of > 30 days after the index revision procedure (odds ratio (OR) 0.24 (95% confidence interval (CI) 0.08 to 0.72); p = 0.008), a repeated DAIR within 90 days (OR 0.37 (95% CI 0.14 to 0.97); p = 0.040), and the use of an immunosuppressive agent (OR 0.13 (95% CI 0.02 to 0.67); p = 0.012) were associated with a significantly reduced success rate. In the culture-positive group, a mismatch between the antibiotic treatment and the susceptibility of the organism was associated with a significantly lower success rate (OR 0.13 (95% CI 0.03 to 0.62); p = 0.007). Conclusion. DAIR is an acceptable form of surgical treatment for patients with a suspected early PJI after revision arthroplasty of the hip or knee. DAIRs performed after a prolonged interval, multiple DAIRs, and antibiotic mismatches were significantly associated with an increased risk of failure. Optimization of the host immune response and the prevention of antibiotic mismatch are modifiable factors that may improve the outcome. The high rate of mismatches was an important finding, underlining the need for a review of the local microbiological data, which might improve the outcome. Cite this article: Bone Joint J 2022;104-B(4):464–471

Aims. Serum inflammatory parameters are widely used to aid in diagnosing a periprosthetic joint infection (PJI). Due to their limited performances in the literature, novel and more accurate biomarkers are needed. Serum albumin-to-globulin ratio (AGR) and serum CRP-to-albumin ratio (CAR) have previously been proposed as potential new parameters, but results were mixed. The aim of this study was to assess the diagnostic accuracy of AGR and CAR in diagnosing PJI and to compare them to the established and widely used marker CRP. Methods. From 2015 to 2022, a consecutive series of 275 cases of revision total hip (n = 129) and knee arthroplasty (n = 146) were included in this retrospective cohort study. Based on the 2021 European Bone and Joint Infection Society (EBJIS) definition, 144 arthroplasties were classified as septic. Using receiver operating characteristic curve (ROC) analysis, the ideal thresholds and diagnostic performances were calculated. The areas under the curve (AUCs) were compared using the z-test. Results. AGR, CAR, and CRP were associated with PJI (p < 0.001). Sensitivities were 62.5% (95% CI 54.3 to 70.0), 73.6% (95% CI 65.8 to 80.1), and 71.5% (95% CI 63.6 to 78.3), respectively. Specificities were calculated with 84.7% (95% CI 77.5 to 89.9), 86.3% (95% CI 79.2 to 91.2), and 87.8% (95% CI 80.9 to 92.4), respectively. The AUC of CRP (0.797 (95% CI 0.750 to 0.843)) was significantly higher than the AUC of AGR (0.736 (95% CI 0.686 to 0.786), p < 0.001), and similar to AUC of CAR (0.799 (95% CI 0.753 to 0.846), p = 0.832). Decreased sensitivities were observed in PJIs caused by low-virulence organisms (AGR: 60%, CAR: 78%) compared to high-virulence pathogens (AGR: 80%, p = 0.042; CAR: 88%, p = 0.158). Higher sensitivities were seen in acute haematogenous (AGR: 83%, CAR: 96%) compared to chronic PJIs (AGR: 54%, p = 0.001; CAR: 65%, p < 0.001). Conclusion. Serum AGR and CAR showed limited diagnostic accuracy (especially in low-grade and chronic infections) and did not outperform the established marker CRP in our study. Hence, neither parameter can be recommended as an additional tool for diagnosing PJI. Cite this article: Bone Joint Res 2024;13(8):372–382

Aims. Intra-articular administration of antibiotics during primary total knee arthroplasty (TKA) may represent a safe, cost-effective strategy to reduce the risk of acute periprosthetic joint infection (PJI). Vancomycin with an aminoglycoside provides antimicrobial cover for most organisms isolated from acute PJI after TKA. However, the intra-articular doses required to achieve sustained therapeutic intra-articular levels while remaining below toxic serum levels is unknown. The purpose of this study is to determine the intra-articular and serum levels of vancomycin and tobramycin over the first 24 hours postoperatively after intra-articular administration in primary cementless TKA. Methods. A prospective cohort study was performed. Patients were excluded if they had poor renal function, known allergic reaction to vancomycin or tobramycin, received intravenous vancomycin, or were scheduled for same-day discharge. All patients received 600 mg tobramycin and 1 g of vancomycin powder suspended in 25 cc of normal saline and injected into the joint after closure of the arthrotomy. Serum from peripheral venous blood and drain fluid samples were collected at one, four, and 24 hours postoperatively. All concentrations are reported in µg per ml. Results. A total of 22 patients were included in final analysis. At one, four, and 24 hours postoperatively, mean (95% confidence interval (CI)) serum concentrations were 2.4 (0.7 to 4.1), 5.0 (3.1 to 6.9), and 4.8 (2.8 to 6.9) for vancomycin and 4.9 (3.4 to 6.3), 7.0 (5.8 to 8.2), and 1.3 (0.8 to 1.8) for tobramycin; intra-articular concentrations were 1,900.6 (1,492.5 to 2,308.8), 717.9 (485.5 to 950.3), and 162.2 (20.5 to 304.0) for vancomycin and 2,105.3 (1,389.9 to 2,820.6), 403.2 (266.6 to 539.7), and 98.8 (0 to 206.5) for tobramycin. Conclusion. Intra-articular administration of 1 g of vancomycin and 600 mg of tobramycin as a solution after closure of the arthrotomy in primary cementless TKA achieves therapeutic intra-articular concentrations over the first 24 hours postoperatively and does not reach sustained toxic levels in peripheral blood. Cite this article: Bone Joint J 2021;103-B(11):1702–1708

Aims. Histology is an established tool in diagnosing periprosthetic joint infections (PJIs). Different thresholds, using various infection definitions and histopathological criteria, have been described. This study determined the performance of different thresholds of polymorphonuclear neutrophils (≥ 5 PMN/HPF, ≥ 10 PMN/HPF, ≥ 23 PMN/10 HPF) , when using the European Bone and Joint Infection Society (EBJIS), Infectious Diseases Society of America (IDSA), and the International Consensus Meeting (ICM) 2018 criteria for PJI. Methods. A total of 119 patients undergoing revision total hip (rTHA) or knee arthroplasty (rTKA) were included. Permanent histology sections of periprosthetic tissue were evaluated under high power (400× magnification) and neutrophils were counted per HPF. The mean neutrophil count in ten HPFs was calculated (PMN/HPF). Based on receiver operating characteristic (ROC) curve analysis and the z-test, thresholds were compared. Results. Using the EBJIS criteria, a cut-off of ≥ five PMN/HPF showed a sensitivity of 93% (95% confidence interval (CI) 81 to 98) and specificity of 84% (95% CI 74 to 91). The optimal threshold when applying the IDSA and ICM criteria was ≥ ten PMN/HPF with sensitivities of 94% (95% CI 79 to 99) and 90% (95% CI 76 to 97), and specificities of 86% (95% CI 77 to 92) and 92% (95% CI 84 to 97), respectively. In rTKA, a better performance of histopathological analysis was observed in comparison with rTHA when using the IDSA criteria (p < 0.001). Conclusion. With high accuracy, histopathological analysis can be supported as a confirmatory criterion in diagnosing periprosthetic joint infections. A threshold of ≥ five PMN/HPF can be recommended to distinguish between septic and aseptic loosening, with an increased possibility of detecting more infections caused by low-virulence organisms. However, neutrophil counts between one and five should be considered suggestive of infection and interpreted carefully in conjunction with other diagnostic test methods. Cite this article: Bone Joint Res 2021;10(8):536–547

The June 2023 Research Roundup³⁶⁰ looks at: Characterizing recurrent infections after one-stage revision for periprosthetic joint infection of the knee; Predicted waiting times for orthopaedic surgery: an urgent need to address the deficit in capacity; Vascular impulse technology versus elevation for reducing the swelling of upper and lower limb joint fractures; Desperate patients will accept higher risks; How long does it take to find a positive culture in periprosthetic joint infection?

The April 2023 Research Roundup³⁶⁰ looks at: Ear protection for orthopaedic surgeons?; Has arthroscopic meniscectomy use changed in response to the evidence?; Time to positivity of cultures obtained for periprosthetic joint infection; Bisphosphonates for post-COVID-19 osteonecrosis of the femoral head; Missing missed fractures: is AI the answer?; Congenital insensitivity to pain and correction of the knee; YouTube and paediatric elbow injuries.

Aims

The aims of this study were to determine the diagnostic yield of image-guided biopsy in providing a final diagnosis in patients with suspected infectious spondylodiscitis, to report the diagnostic accuracy of various microbiological tests and histological examinations in these patients, and to report the epidemiology of infectious spondylodiscitis from a country where tuberculosis (TB) is endemic, including the incidence of drug-resistant TB.

Osteoarticular infections (OAI) are a common cause of morbidity in children, and as opposed to adults is usually caused by haematogenous spread. The bacteriology of OAI in children is not well described in the South African context, therefore this study was designed to determine the bacteriology of OAI in our population. All patients that underwent surgery for the treatment of OAI over a 3-year period were identified and those with positive cultures where organisms were identified from tissue, pus, fluid or blood were included. Duplicate cultures from the same patient were excluded if the organism and antibiotic susceptibility profile was the same. Patients were categorised according to age and class of infection (Septic arthritis, acute osteomyelitis, fracture related infection, post-operative sepsis and chronic osteomyelitis) and organisms were stratified according to these categories. We identified 132 organisms from 123 samples collected from 86 patients. Most cultured organisms were from children older than 3-years with acute haematogenous septic arthritis, osteomyelitis, or both. Methicillin sensitive Staphylococcus aureus accounted for 56% (74/132) of organisms cultured. There were no cases of MRSA. The Enterobacterales accounted for 17% (22/132) of organisms cultured, mostly in the fracture related and post-operative infection groups. Of these, 6 each were extended spectrum B-lactamase producers and AmpC producers. There were no carbapenemase producing Enterobacterales. Kingella kingae was not isolated in any patient. Methicillin sensitive S. aureus is the most common infecting organism in paediatric OAI and an anti-staphylococcal penicillin such as cloxacillin or flucloxacillin is the most appropriate empiric treatment for haematogenous OAI in our environment. In fracture related or post-operative infections, Enterobacterales were more frequently cultured, and treatment should be guided by culture and susceptibility results

Aims. The aim of this study was to determine the extent to which patient demographics, clinical presentation, and blood parameters vary in Kingella kingae septic arthritis when compared with those of other organisms, and whether this difference needs to be considered when assessing children in whom a diagnosis of septic arthritis is suspected. Methods. A prospective case series was undertaken at a single UK paediatric institution between October 2012 and November 2018 of all patients referred with suspected septic arthritis. We recorded the clinical, biochemical, and microbiological findings in all patients. Results. A total of 160 patients underwent arthrotomy for a presumed septic arthritis. Of these, no organism was identified in 61 and only 25 of these were both culture- and polymerase chain reaction (PCR)-negative. A total of 36 patients did not undergo PCR analysis. Of the remaining 99 culture- and PCR-positive patients, K. kingae was the most commonly isolated organism (42%, n = 42). The knee (n = 21), shoulder (n = 9), and hip (n = 5) were the three most commonly affected joints. A total of 28 cases (66%) of K. kingae infection were detected only on PCR. The mean age of K. kingae-positive cases (16.1 months) was significantly lower than that of those whose septic arthitis was due to other organisms (49.4 months; p < 0.001). The mean CRP was significantly lower in the K. kingae group than in the other organism group (p < 0.001). The mean ESR/CRP ratio was significantly higher in K. kingae (2.84) than in other infections (1.55; p < 0.008). The mean ESR and ESR/CRP were not significantly different from those in the 'no organism identified' group. Conclusion. K. kingae was the most commonly isolated organism from paediatric culture- and/or PCR-positive confirmed septic arthritis, with only one third of cases detected on routine cultures. It is important to develop and maintain a clinical suspicion for K. kingae infection in young patients presenting atypically. Routine PCR testing is recommended in these patients. Cite this article: Bone Joint J 2021;103-B(3):584–588

Aim. We reviewed a cohort of individuals with recurrent orthopaedic infection to describe the relative rates of microbial persistence vs re-infection at recurrence surgery. Method. A cohort of 125 individuals with recurrent infection (prosthetic joint infection, fracture-related infection and osteomyelitis) from two centres in the UK between 2007 and 2021. Electronic patient records were reviewed to identify culture results from surgical samples at index surgery and the next operation for recurrent infection. Antibiotic sensitivity results were recorded as sensitive, intermediate or resistant according to contemporary sensitivity testing guidelines. Results. Among patients with recurrent infection, 78/125 (62.4%) were male, with a median age 64 years (IQR 51–73y). 76 had prosthetic joint infection, and 49 had fracture related infection or osteomyelitis. Culture results at index procedure showed the most frequently isolated species were Staphylococci (Table 1). A single species was isolated in 75/125 (60%) and mixed species in 36/125 (28.8%). No organisms were cultured in 14/125 (11.2%). At re-operation 48/125 (38.4%) individuals had an organism from the same species or group as at the index operation. In 49/125 (39.2%), none of the organisms isolated at re-operation were grown at first operation. In 28/125 (22.4%), re-operative cultures yielded no growth. For each species isolated at the index procedure, the proportion with the same, different or no organisms isolated at the next procedure were reviewed (Table 1). Staphylococci (including S. aureus and coagulase-negative staphylococci) and Pseudomonas species showed the highest rate of persistence at the species level. Among coagulase-negative staphylococci, changes in antimicrobial sensitivity that make it unclear if these infections were truly persistent, or represented re-infection. Conclusions. Infection with different organisms was seen at similar rates (39.2% vs 38.4%) to persistent infection with the same species in this cohort. Staphylococcus aureus is the organism most likely to be persistently identified in recurrent infections

Introduction. Diabetic foot disease is a major public health problem with an annual NHS expenditure in excess of £1 billion. Infection increases risk of major amputation fivefold. Due to the polymicrobial nature of diabetic foot infections, it is often difficult to isolate the correct organism with conventional culture techniques, to deliver appropriate narrow spectrum antibiotics. Rapid DNA-based technology using multi-channel arrays presents a quicker alternative and has previously been used effectively in intensive care and respiratory medicine. Methods. We gained institutional and Local Ethics Committee approval for a prospective cohort study of patients with clinically infected diabetic foot wounds. They all had deep tissue samples taken in clinic processed with conventional culture and real-time PCR TaqMan array. Results. 50 samples were taken from 39 patients between October 2020 and March 2022. 84% of patient were male, 88% had type 2 diabetes. The ulcers were of variable chronicity prior to sampling (range 1–113 weeks) and mean HbA1c was 67.2mmol/mol. Ulcers were on the heel (3), midfoot (6) and forefoot (41). Minimum follow up was 3 months. 6 ulcers healed, 24 patients were admitted due to foot disease, there were 2 major amputations and 4 deaths. TaqMan array results were available a mean of 4.3 days earlier than culture results. 9 patients had negative conventional cultures and 8 were negative onarray testing. 17 patients had the same organisms detected on culture and array. 16 of these 17 had additional organisms detected by array. The most frequent organisms detected on array that were not detected by culture were Staphylococcus spp., Enterobacter, Pseudomonas and fungi. Conclusion. TaqMan array shows promise in detecting infecting organisms from diabetic foot wounds and providing earlier results than standard culture, which may enable appropriate and timely antibiotic therapy

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

Aim. Surgical management of PJI remains challenging with patients failing treatment despite the best efforts. An important question is whether these later failures reflect reinfection or the persistence of infection. Proponents of reinfection believe hosts are vulnerable to developing infection and new organisms emerge. The alternative hypothesis is that later failure is a result of an organism that was present in the joint but was not picked up by initial culture or was not a pathogen initially but became so under antibiotic pressure. This multicenter study explores the above dilemma. Utilizing next-generation sequencing (NGS), we hypothesize that failures after two-stage exchange arthroplasty can be caused by an organism that was present at the time of initial surgery but not isolated by culture. Method. This prospective study involving 15 institutions collected samples from 635 revision total hip(n=310) and knee(n=325) arthroplasties. Synovial fluid, tissue and swabs were obtained intraoperatively for NGS analysis. Patients were classified per 2018 Consensus definition of PJI. Treatment failure was defined as reoperation for infection that yielded positive cultures, during minimum 1-year follow-up. Concordance of the infecting pathogen cultured at failure with NGS analysis at initial revision was determined. Results. Among the total cohort, 203 revisions were considered infected and 432 were aseptic (based on ICM-criteria). Of the infected cases, 157 were NGS-positive and 46 NGS-negative. Twenty-nine ICM-positive patients (29/157;18.5%) failed by reoperation with an organism confirmed on culture. In 23 of these (23/29;79.3%), the organism at failure was present on NGS at initial revision. The remaining 6 cases detected discordant organisms between initial NGS and culture at failure. Of the 432 ICM-negative patients, NGS identified microbes in 48.1% (208/432) of “aseptic” revisions, and 17 of these failed. Thirteen of the 17 failures (76.5%) were due to an organism previously detected by NGS at initial revision. Conclusion. Our collaborative findings suggest that most failures (79.3%) by infection recurrence could be attributed to an organism previously detected by NGS at index revision surgery

Aims. Single-stage revision total knee arthroplasty (rTKA) is gaining popularity in treating chronic periprosthetic joint infections (PJIs). We have introduced this approach to our clinical practice and sought to evaluate rates of reinfection and re-revision, along with predictors of failure of both single- and two-stage rTKA for chronic PJI. Methods. A retrospective comparative cohort study of all rTKAs for chronic PJI between 1 April 2003 and 31 December 2018 was undertaken using prospective databases. Patients with acute infections were excluded; rTKAs were classified as single-stage, stage 1, or stage 2 of two-stage revision. The primary outcome measure was failure to eradicate or recurrent infection. Variables evaluated for failure by regression analysis included age, BMI, American Society of Anesthesiologists grade, infecting organisms, and the presence of a sinus. Patient survivorship was also compared between the groups. Results. A total of 292 consecutive first-time rTKAs for chronic PJI were included: 82 single-stage (28.1%); and 210 two-stage (71.9%) revisions. The mean age was 71 years (27 to 90), with 165 females (57.4%), and a mean BMI of 30.9 kg/m. 2. (20 to 53). Significantly more patients with a known infecting organism were in the single-stage group (93.9% vs 80.47%; p = 0.004). The infecting organism was identified preoperatively in 246 cases (84.2%). At a mean follow-up of 6.3 years (2.0 to 17.6), the failure rate was 6.1% in the single-stage, and 12% in the two-stage groups. All failures occurred within four years of treatment. The presence of a sinus was an independent risk factor for failure (odds ratio (OR) 4.97; 95% confidence interval (CI) 1.593 to 15.505; p = 0.006), as well as age > 80 years (OR 5.962; 95% CI 1.156 to 30.73; p = 0.033). The ten-year patient survivorship rate was 72% in the single-stage group compared with 70.5% in the two-stage group. This difference was not significant (p = 0.517). Conclusion. Single-stage rTKA is an effective strategy with a high success rate comparable to two-stage approach in appropriately selected patients. Cite this article: Bone Joint J 2021;103-B(8):1373–1379

Prosthetic joint infection (PJI) remains one of the most challenging complications to manage following total joint arthroplasty (TJA). There is a paucity of published data on the management of PJI in smaller, rural hospital settings. In this study, we investigate [1] the success rate of surgical management for PJI following TJA and [2] the microbiology of infecting organisms in this unique geographical environment. We performed a retrospective single-centre study at a rural hospital (Southland Hospital, Invercargill, New Zealand) over a 3-year period (2019 to 2022). All patients presenting with a first episode of PJI fulfilling Musculoskeletal Infection Society criteria after hip or knee arthroplasty were included. All patients had a minimum follow up of 6 months. Treatment success was defined eradication of infection. Twenty-one cases (14 hips and 7 knees) were identified. These were managed with Debridement, antibiotics, and implant retention (DAIR) procedure (n=14, 67%), single-stage revision (n=6, 29%), or long-term suppressive antibiotics (n=1, 4%). Of the DAIR patients, infection recurred in 50% and underwent subsequent revision. Of the single-stage revision patients, 17% failed and underwent subsequent revision. The overall success rate was 90%. Methicillin-sensitive Staphylococcus aureus (MSSA) was the most isolated pathogen (57%,) with no methicillin-resistance Staphylococcus aureus (MRSA) identified. Overall, 90% of infecting organisms were cefazolin sensitive. These results suggest that management of PJI is a safe and viable treatment option when performed in a rural hospital setting, with comparable treatment success rates to urban centres. The incidence of MRSA is low in this setting. Rates of antibiotic resistance were relatively low and most organisms were sensitive to cefazolin, the routine antibiotic used in prophylaxis

Aims. The management of periprosthetic joint infection (PJI) after total knee arthroplasty (TKA) is challenging. The correct antibiotic management remains elusive due to differences in epidemiology and resistance between countries, and reports in the literature. Before the efficacy of surgical treatment is investigated, it is crucial to analyze the bacterial strains causing PJI, especially for patients in whom no organisms are grown. Methods. A review of all revision TKAs which were undertaken between 2006 and 2018 in a tertiary referral centre was performed, including all those meeting the consensus criteria for PJI, in which organisms were identified. Using a cluster analysis, three chronological time periods were created. We then evaluated the antibiotic resistance of the identified bacteria between these three clusters and the effectiveness of our antibiotic regime. Results. We identified 129 PJIs with 161 culture identified bacteria in 97 patients. Coagulase-negative staphylococci (CNS) were identified in 46.6% cultures, followed by Staphylococcus aureus in 19.8%. The overall resistance to antibiotics did not increase significantly during the study period (p = 0.454). However, CNS resistance to teicoplanin (p < 0.001), fosfomycin (p = 0.016), and tetracycline (p = 0.014) increased significantly. Vancomycin had an 84.4% overall sensitivity and 100% CNS sensitivity and was the most effective agent. Conclusion. Although we were unable to show an overall increase in antibiotic resistance in organisms that cause PJI after TKA during the study period, this was not true for CNS. It is concerning that resistance of CNS to new antibiotics, but not vancomycin, has increased in a little more than a decade. Our findings suggest that referral centres should continuously monitor their bacteriological analyses, as these have significant implications for prophylactic treatment in both primary arthroplasty and revision arthroplasty for PJI. Cite this article: Bone Joint J 2021;103-B(6 Supple A):171–176

Aim. There are no definitive criteria for the definition of osteomyelitis in the hand and wrist and published case series are small. It remains a relatively uncommon, but difficult to treat problem. We present a series of 30 cases from 2016 to 2021 from a tertiary referral centre. We propose that the principles of thorough surgical debridement, dead space management, skeletal stabilisation and culture driven antibiotic therapy are the key to management of osteomyelitis in the hand and wrist. In addition, we show how these basic principles can be used for both functional and aesthetic impact for the wrist and digits with illustrated cases. Methods. We conducted a retrospective chart review over a 6 year period and recorded the site of the infection, the soft tissue and bony management, whether antibiotic eluting bone filler was used, the isolated bacterial species, the number of surgical procedures undertaken to treat the infection and the success rate for clearing the infection. Results. 17/30 cases had pre-existing metalwork in-situ. There were 19 phalangeal/metacarpal infections and 11 carpal infections. 24 patients had native joint involvement. A drug eluting bone void filler was used in 23/30 cases in order to manage the dead space. In 7/30 cases had polymicrobial organisms isolated, 15/30 had only one organism cultured. The most common organism cultured was Staphylococcus aureus. Complete resolution of osteomyelitis or joint infection was achieved in 29/30 cases with follow up ranging from six months to six years. 2/30 cases required thorough debridement of the distal phalanx; bone void filler provided an aesthetically optimal result to improve fingertip contour whilst managing the dead space. Conclusion. Osteomyelitis of the hand and wrist is optimally managed with thorough surgical debridement, dead space management with a drug eluting bone void filler, skeletal stabilisation and culture directed antibiotic therapy. In addition, the bone void filler provides pulp support and improves the aesthetic contour of fingertips in which distal phalangeal osteomyelitis was successfully treated

Aim. Local antibiotic treatment for bone and joint infections offers direct delivery of high concentrations of antibiotics with reduced systemic exposure and favourable safety profile. However, the possibility of prolonged release of antibiotics at sub-therapeutic levels creates concern about the possible development of antimicrobial resistance. We investigated patients with recurrent bone and joint infection for evidence of antimicrobial resistance emerging from the use of local antibiotics. Method. 125 patients with recurrent infection (prosthetic joint infection, fracture related infection and osteomyelitis) in the UK between 2007 and 2021 were identified. Electronic patient records (including operative notes, pathology results and prescriptions) were reviewed to extract site of infection, date of surgery, the use of local antibiotics, culture results, empiric and definitive antibiotic therapy. All antibiotic sensitivity results were recorded as sensitive, intermediate or resistant according to contemporary guidelines (BSAC and EUCAST). Results. Local antibiotics were used in 74/125 (59.2%) of patients. Agents used were Gentamicin 53/125 (42.4%), Tobramycin 18/125 (14.4%), and vancomycin in 19/125 (15.2%). Combined gentamicin and vancomycin usage was seen in 16/125 patients (12.8%). Gentamicin non-sensitivity was common in this cohort with frequent aminoglycoside use. At index procedure, a Gentamicin non-sensitive organism was cultured in 51/125 patients (40.8%). At re-operation this proportion was lower: 40/125 (32%). There was no statistically significant difference in the rate of Gentamicin resistance at reoperation comparing patients who previously received local aminoglycosides with those who had not (21/71, 29.8% vs 19/54, 35.2% p=0.6, chi-squared test). In 48/125 (38.4%) of patients, the same species was isolated during the index and recurrence surgery. We identified 7 cases with new aminoglycoside resistance arising at the second procedure. In 2/7 – S. aureus and E. faecalis - aminoglycoside resistance was the only change in antimicrobial sensitivity. In 5/7, there were at least 2 additional changes in observed antimicrobial sensitivity. 3/74 (4%) of cases who initially received local aminoglycoside cultured organisms with aminoglycoside resistance at recurrence. 4/51 (7.8%) of those who did not receive local or systemic aminoglycoside at index surgery cultured resistant organisms (chi square 0.82; p=0.365). Conclusions. As a group, patients whose treatment for orthopaedic infection included local antibiotics did not exhibit higher rates of specific antimicrobial resistance compared with those not treated with local antibiotics. However we did identify cases where Gram positive bacteria developed aminoglycoside resistance regardless of their initial antimicrobial therapy. This should be considered in antimicrobial choice during surgery for recurrence

Treatment of periprosthetic joint infection (PJI) can include local delivery of antibiotics. A frequently used medium is absorbable calcium sulphate beads. The aims of this study were to:. identify how often organisms in infected THRs are sensitive to the added antibiotics. establish the incidence of persistent wound discharge and hypercalcaemia. All patients who received an antibiotic loaded calcium sulphate carrier (Stimulan, Biocomposites, Keele, UK) for either confirmed infection, presumed infection or for prophylaxis between July 2015 and July 2020 were included. Stimulan use was at the discretion of the surgeon, and between 10 and 40cc was used. In the absence of a known organism we routinely used 1g vancomycin and 240mg gentamicin per 10 cc of calcium sulphate. Post-operative sensitivities for all organisms cultured were compared to the antibiotics delivered locally. Persistent wound drainage was defined as discharge beyond the third postoperative day. Patients had serum calcium measured if they developed symptoms consistent with hypercalcaemia (Ca >2.6 mmol/L) or the clinical team felt they were at high risk. 189 patients (mean age 66.9 years, mean BMI 28.9, 85 male, 104 female) were included. 11 patients had a native joint septic arthritis, 42 presented with acute PJI and 136 presented with chronic PJI. 133 patients grew an organism, of which 126 were sensitive to the added antibiotics. Of the seven patients with resistant growth five had vancomycin-resistent Enterococcus, one Pseudomonas and one multi-organism growth including coagulase negative Staphylococcus. 40 patients experienced persistent wound discharge, with eight requiring re-operation. All other cases settled with dressing management. 12 patients developed hypercalcaemia (3/64 10cc, 7/117 20cc, 0/2 30cc and 2/6 40cc). The peak calcium reading ranged between the second and twelfth post-operative day. The addition of vancomycin and gentamicin to absorbable calcium sulphate covers the majority of organisms found in culture positive infection in our cohort. It also appears safe, with an acceptable incidence of hypercalcaemia or wound discharge. Further work is required to identify patients at greatest risk of culturing resistant organisms or delayed wound healing

Most patients treated at our clinical setting present during chronic osteomyelitis stage, which is anecdotally likely to be poly-microbial. Adults with poly-microbial infection have a predilection for gram-negative bacteria and anaerobes, a scenario that hypothetically leads to a higher morbidity of poly-microbial osteomyelitis following trauma. Our study looks into the epidemiology of poly-microbial osteomyelitis treated at our Tumour and Infection unit. Retrospective study of patients treated for osteomyelitis from 2016 to 2020. Records of eligible patients were retrieved for examination. Demographics such as age, sex and race were recorded. Clinical presentation, organisms cultured, including their anti-microbial sensitivities were documented. There were 63 participants in the study. 31 (49.21%) had mono-microbial osteomyelitis with 32 (50.79%) having poly-microbial osteomyelitis. Majority of the poly-microbial patients presented with a sinus (68.75%) mostly located in the tibia (50%). Multiple mixed pathogens (both gam-positive and gram-negative) were cultured in our patients and this comprised 71.21% of the total bacteria cultured. Staphylococcus Aureus was the commonest bacteria (30%) isolated, followed by Enterococcus faecalis (12%). The commonest gram-negative bacteriae cultured was Enterococcus cloacae (10%) followed by Acinetobacter baumannii (7%). Most enterobacteriacae species were sensitive to Ertapenem and Ceftazidime. A slightly higher incidence of poly-microbial osteomyelitis was found in our study than that reported in literature. Furthermore, our study demonstrated a wide variety of organisms found in poly-microbial osteomyelitis, with a large contribution made by gram-negative anaerobic rod-shaped bacteria

Introduction. Introduction: Pin site infection is a common complication during treatment with a circular frame external fixator and increases time and support patients require from the limb reconstruction team. Wound swabs were not routinely sent by the clinical nurse specialists prior to this study, with most pin site infections treated as Staphylococcus aureus with flucloxacillin (clindamycin in penicillin allergy). The aim of this study was to ascertain whether routine sending of wound swabs in pin site infection would change antibiotic treatment. Materials & Methods. Materials and Method: Patients presenting at clinic or physiotherapy with clinical signs of pin site infection were assessed using the Maz Oxford Nuffield (MON) Pin Site Infection Grading System© (OUH, 2021). Antibiotics were commenced as per unit guidelines and swabs sent for microscopy, culture and sensitivity. Results. Results: There were forty patients treated with pin site infections. Swab results showed S. aureus in 60% (N=24), other organisms in 15% (N=6) and no growth or mixed skin organisms in 10% (N=10). Flucloxacillin was prescribed to 77.5% (n=31) of patients with the remaining 22.5% (n=9) of patients receiving clindamycin (due to allergy) or rifampicin and ciprofloxacin (due to a previous MRSA diagnosis). Antibiotic management was subsequently changed in only 5% (n=2) of patients due to one patient with a new MRSA diagnosis and one patient growing Enterobacter in three pin sites tested. Conclusions. Conclusion: This study has shown that routine swab testing of pin sites does not usually change antibiotic management but should still be used in multiple, severe or unresolving pin site infections

Introduction. Surgical management of PJI remains challenging with patients failing treatment despite the best efforts. An important question is whether these later failures reflect reinfection or the persistence of infection. Proponents of reinfection believe hosts are vulnerable to developing infection and new organisms emerge. The alternative hypothesis is that later failure is a result of an organism that was present in the joint but was not picked up by initial culture or was not a pathogen initially but became so under antibiotic pressure. This multicenter study explores the above dilemma. Utilizing next-generation sequencing (NGS), we hypothesize that failures after two stage exchange arthroplasty can be caused by an organism that was present at the time of initial surgery but not isolated by culture. Methods. This prospective study involving 15 institutions collected samples from 635 revision total hip (n=310) and knee (n=325) arthroplasties. Synovial fluid, tissue and swabs were obtained intraoperatively for NGS analysis. Patients were classified per 2018 Consensus definition of PJI. Treatment failure was defined as reoperation for infection that yielded positive cultures, during minimum 1-year follow-up. Concordance of the infecting pathogen cultured at failure with NGS analysis at initial revision was determined. Results. Among the total cohort, 203 revisions were considered infected and 432 were aseptic (based on ICM-criteria). Of the infected cases, 157 were NGS-positive and 46 NGS-negative. Twenty-nine ICM-positive patients (29/157;18.5%) failed by reoperation with an organism confirmed on culture. In 23 of these (23/29;79.3%), the organism at failure was present on NGS at initial revision. The remaining 6 cases detected discordant organisms between initial NGS and culture at failure. Of the 432 ICM-negative patients, NGS identified microbes in 48.1% (208/432) of “aseptic” revisions, and 17 of these failed. Thirteen of the 17 failures (76.5%) were due to an organism previously detected by NGS at initial revision. Conclusion. Our collaborative findings suggest that most failures (79.3%) by infection recurrence could be attributed to an organism previously detected by NGS at index revision surgery. For any figures or tables, please contact the authors directly

Between 2016–2019, 4 patients developed hip infections post-hemiarthroplasty. However, between 2020–2021 (Covid-19 pandemic period), 6 patients developed hip infections following hip hemiarthroplasty. The purpose of the investigation is to establish the root causes and key learning from the incident and use the information contained within this report to reduce the likelihood of a similar incident in the future. 65 patients presented with a neck of femur fracture during Covid-19 pandemic period between 2020–2021, 26 had hip hemiarthroplasty of which 6 developed hip infections. Medical records, anaesthetic charts and post-hip infections guidelines from RCS and NICE were utilised. Proteus, Enterococci and Strep. epidermis were identified as the main organisms present causing the hip infection. The average number of ward moves was 4 with 90% of patients developing COVID-19 during their hospital stay. The chance of post-operative wound infection were multifactorial. Having had 5 of 6 patients growing enterococci may suggest contamination of wound either due to potential suboptimal hygiene measures, inadequate wound management /dressing, potential environmental contamination if the organisms (Vancomycin resistant enterococci) are found to be of same types and potential hospital acquired infection due to inadequate infection control measures or suboptimal hand hygiene practices. 3 of the 5 patients grew Proteus, which points towards suboptimal hygiene practices by patients or poor infection control practices by staff. Lack of maintenance of sterility in post op wound dressings alongside inexperience of the handling of post-operative wound in non-surgical wards; multiple ward transfers exceeding the recommended number according to trust guidelines especially due to pandemic isolation measures and COVID-19 infection itself had resulted in an increased rate of hip infections during the COVID-19 pandemic. Multidisciplinary team education and planned categorisation and isolation strategy is essential to minimise the rate of further hip infections during the pandemic period in future

No single test has demonstrated absolute accuracy in the diagnosis of periprosthetic joint infection (PJI). Leukocyte esterase (LE) is a synovial marker that has proven utility in the diagnosis of PJI. The purpose of this prospective study was to (1) identify the optimal cutoff for the use of LE in the diagnosis of PJI and (2) determine whether performance of the LE strip test varied by infecting organism. This prospective study enrolled 1,015 patients undergoing hip or knee revision arthroplasty at a single institution from 2009 to September 2021. PJI was defined using a modified version of 2018 International Consensus Meeting (ICM) criteria that excluded LE when calculating the ICM score. Receiver operating characteristic curves were used to assess the utility of the LE strip test in the diagnosis of PJI. 973 patients were included in the analyses. 246 (25.4%) were classified as ICM-positive and 727 (74.6%) were classified as ICM-negative. An LE cutoff of “1+” (AUC 0.819, sensitivity 73.2%, specificity 90.6%) had superior accuracy to an LE cutoff of “2+” (AUC 0.713, sensitivity 43.9%, specificity 98.8%) in the overall diagnosis of PJI (p<0.001). When stratifying by organism type, an LE cutoff of “1+” had the best diagnostic utility for PJI caused by methicillin resistant Staphylococcus aureus (AUC 0.888, sensitivity 87.0%, n=23) followed by Streptococcus spp. (AUC 0.882, sensitivity 85.7%, n=28), coagulase negative Staphylococci (AUC 0.836, sensitivity 76.6%, n=47), methicillin sensitive Staphylococcus aureus (AUC 0.806, sensitivity 70.6%, n=34), culture negative (AUC 0.793, sensitivity 67.9%, n=56), and gram negative rods (AUC 0.763, sensitivity 61.9%, n=21). To our knowledge, this is the largest study evaluating the utility of the LE strip test in the diagnosis of PJI. Based on our findings, it appears that a “1+” cutoff has higher diagnostic utility than a cutoff of “2+”

The benefits of cell salvage autotransfusion are well reported. There is a common non-evidenced belief amongst revision arthroplasty surgeons that auto-transfusion is potentially contraindicated in infected revisions. The aim is to study the immediate and delayed outcomes of using cell saver on patients undergoing PJI surgery. Prospective cohort service evaluation registered with the local audit department. 20 PJI cases in 18 patients where cell saver was used over a period of 4 years. Intraoperative fluid and tissue samples were taken for culture. Blood culture from salvaged blood pre and post leucodepletion filter were sent for microbiological analysis. Data on type of surgery, blood loss, further allogenic transfusion and SIRS response was collected. Success of infection clearance was assessed using 2019 MSIS ORT. Five patients receiving autologous blood in non-infection cases were used as controls. Mean age for the PJI group was 67.7 years, 67% female. 11 patients (67%) had 1st stage surgery and 5 (25%) underwent 2nd stage whereas 4 patients had single stage surgery. The mean calculated blood loss was 1398 mls (range 400–3000mls). 6 Patients required further allogenic transfusion. 16 patients received blood via a leuco-depletion filter. The same organism grown from tissues was identified in post-filter blood in 8/17 patients (47%). 2/20 have grown a different organism in post-filtered blood, _P.Acne._. 2 patients developed SIRS upon auto-transfusion, however one was thought to be secondary to cementing. The control group had 443 mls mean amount of blood loss and 1 patient developed a SIRS response. 14/20 (70%) patients had successful clearance of infection (tier 1) 2 patients died prior to undergoing 2nd stage. Using cell saver did not impact main outcome of infection clearance in PJI surgery. We would advocate its routine usage whilst avoiding direct collection of heavily contaminated blood

Aims. The aim of this study was to determine if the local delivery of vancomycin and tobramycin in primary total knee arthroplasty (TKA) can achieve intra-articular concentrations exceeding the minimum inhibitory concentration thresholds for bacteria causing acute prosthetic joint infection (PJI). Methods. Using a retrospective single-institution database of all primary TKAs performed between January 1 2014 and May 7 2019, we identified patients with acute PJI that were managed surgically within 90 days of the initial procedure. The organisms from positive cultures obtained at the time of revision were tested for susceptibility to gentamicin, tobramycin, and vancomycin. A prospective study was then performed to determine the intra-articular antibiotic concentration on postoperative day one after primary TKA using one of five local antibiotic delivery strategies with tobramycin and/or vancomycin mixed into the polymethylmethacrylate (PMMA) or vancomycin powder. Results. A total of 19 patients with acute PJI after TKA were identified and 29 unique bacterial isolates were recovered. The mean time to revision was 37 days (6 to 84). Nine isolates (31%) were resistant to gentamicin, ten (34%) were resistant to tobramycin, and seven (24%) were resistant to vancomycin. Excluding one Fusobacterium nucleatum, which was resistant to all three antibiotics, all isolates resistant to tobramycin or gentamicin were susceptible to vancomycin and vice versa. Overall, 2.4 g of tobramycin hand-mixed into 80 g of PMMA and 1 g of intra-articular vancomycin powder consistently achieved concentrations above the minimum inhibitory concentrations of susceptible organisms. Conclusion. One-third of bacteria causing acute PJI after primary TKA were resistant to the aminoglycosides commonly mixed into PMMA, and one-quarter were resistant to vancomycin. With one exception, all bacteria resistant to tobramycin were susceptible to vancomycin and vice versa. Based on these results, the optimal cover for organisms causing most cases of acute PJI after TKA can be achieved with a combination of tobramycin mixed in antibiotic cement, and vancomycin powder. Cite this article: Bone Joint J 2020;102-B(6 Supple A):163–169

Aim. Mega-endoprosthesis over the last two decades have played a significant role in management of non-neoplastic cases for limb salvage for a variety of indications involving bone loss, infection, fracture and failed revision surgery. This is a retrospective case control study comparing outcomes of Mega-Endoprosthesis (MEP) in non-neoplastic cases with periprosthetic joint infections (PJI), with previous history of PJI and aseptic revision. Failure was defined as persistence/recurrence of infection, all cause revision, and antibiotic suppression during the follow up period. Secondary aims were identification of causative organisms, resistance profile and causative factors for revision surgery. Method. A total of 122 patients undergoing 133 MEPs were identified between January 2012 and December 2020. 60 procedures were categorised as group 1 (infection; 50%), 20 as group 2 (previous history of infection; 16.7%), and 53 controls (no infection; 44.2%). Mean age of the cohort was 70.97 years (37.16–94.17), with a mean follow-up of 44.5 months (0.2–179) including patients lost to follow up. Results. Overall failure rate was 71/133 53.3% (group 1 39/60 (55.56%), group 2 12/20 (60%) and controls 20/53 (37.7%)). Thirteen patients died in the first 2 years (five in group 1, one in group 2 & seven in controls). The most common postoperative infection was polymicrobial followed by Coagulase Negative Staphylococcus Species (CoNS) and Methicillin Sensitive Staphylococcus aureus (MSSA). Nineteen patients had polymicrobial PJI (Eighteen in group 1 and one in control). CoNS led to postoperative infection in Fifteen patients (six in group 1, five in group 2 and four in control group). MSSA was the pathogen in four patients (three in group-1 and one in the control group). The same organisms were responsible for recurrent infection in fourteen patients in group 1 and one patient in group 2. Limb salvage was achieved in 96.2% overall (95% group 1, 90% group 2, 100% control group). Conclusions. MEPs in the context of PJI have a significant risk of failure however they play an important role in limb salvage. Patients should be counselled appropriately prior to surgery

Abstract. Background. Prosthetic joint infection (PJI) is a significant cause of morbidity and mortality following knee replacement surgery. Identifying the causative agent(s) and their antibiotic sensitivities is critical in determining the choice of treatment methods used and the likelihood of successful eradication. This study aimed to investigate:. Whether biopsy alone was superior to aspiration alone in specificity and sensitivity for diagnosing PJI following knee replacement. Whether biopsy identifies the same microbiological flora as aspiration. Methods. We identified consecutive patients passing through our knee infection Multi-Disciplinary Team meeting between December 2014 and March 2020. Data was collated data retrospectively using electronic records. Statistical analysis was performed using Stata (Timberlake, February 2020). Results. 65 of 100 patients identified had both pre-operative aspiration and biopsy. In 29% of positive patients, biopsy identified new or additional organisms not previously identified by aspiration. Aspiration had a sensitivity of 70%, specificity of 88%, positive predictive value of 90.3% and negative predictive value of 64.7%. Biopsy had a sensitivity of 97.5%, specificity of 88%, positive predictive value of 92.9% and negative predictive value of 95.7%. Conclusion. Biopsy is superior to aspiration in the diagnosis of PJI and can be performed safely and successfully. It identifies organisms when aspiration may be negative and identifies additional microorganisms in a polymicrobial setting not identified by aspiration alone (29% of positive cases). We would recommend, where possible, aspiration and biopsy as routine pre-operative sampling in order to identify all causative agents and their susceptibilities prior to embarking on revision surgery

Aims. The microbiological detection of microorganisms plays a crucial role in the diagnosis as well as in the targeted systemic and local antibiotic therapy of periprosthetic infections (PJI). Despite extensive efforts to improve the sensitivity of current culture methods, the rate of culture-negative infections is approximately 10–20% of all PJI. This study investigates an preanalytical algorithm (culture collection and direct processing in the OR) to potentially increasing culture yield in patients with PJI. Methods. Patients undergoing staged revision arthroplasty for PJI in our hospital between October 2021 and 2022 were included in this prospective pilot study. Intraoperatively twenty tissue samples were collected and distributed among 4 groups. Tissue samples were prepared according to standard without medium and in thioglycolate medium at 3 different temperatures (room temperature, 4°C, 37° for 24h before transport to microbiology) directly in the OR. The removed implants were sonicated. Cultures were investigated on days 1, 3, 7, 12, 14 for possible growth. All grown organism, the number of positive samples and the time to positivity were recorded and compared. Results. 71 patients were included (age, gender). Compared to the standard procedure the thioglycolate broth at 37°C was significantly more often culture-negative (p=0.031). No significant differences in the frequency of culture-negative samples were detected in the other groups. 8.4% (6/71) patients were culture negative in the standard culture but positive in the thioglycolate samples. In contrast, 7% (5/71) were culture negative in the thioglycolate samples but had bacterial detection in the standard approach. In 4.7% (3/63) of the patients, only the sonication showed growth, whereas 25.4% (16/63) had no growth in sonication fluid but in one of the cultures. For S. caprae, there was a significantly different distribution (p=0.026) with more frequent detection in the group with thioglycolate at 37°C. The standard procedure (p=0.005) and sonication (p=0.023) showed a shorter time to positivity of the culture compared to the thioglycolate approach at 4°C. Conclusions. No general differences could be shown between the standard preparation and the thioglycolate preparation; in particular, storage at different temperatures does not seem to result in any difference. For individual cases (8% in this study), bacterial growth was detected in the thioglycolate group that would have been culture-negative otherwise. There might be organism dependent differences in growth in different media

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. At our tertiary orthopaedic centre, mycobacterial cultures are routinely performed on bone and joint samples sent for bacterial culture. We have previously described the prevalence Mycobacterium tuberculosis Complex (MTBC) in these samples. Here, we describe the prevalence of non-tuberculous mycobacteria (NTM). We calculate the number needed to test to identify one previously undiagnosed mycobacterial bone or joint infection. Methods. Samples taken during a single procedure were pooled in one BACTEC MGIT culture. From laboratory records, we ascertained the number of mycobacterial cultures performed, the number positive for MTBC or NTM, and characteristics of individuals from whom mycobacteria were isolated. We collected the same data from 100 individuals with negative mycobacterial cultures. Results presented here are from interim analysis. Results. Excluding sample types that were clearly not bone or joint samples, 6162 mycobacterial cultures were performed between 4 July 2017 and 30 September 2022. Twenty-two patients had MTBC and 6 patients had NTM newly isolated from bone or joint samples placed in mycobacterial culture, with a further patient having both M. tuberculosis and M. avium isolated. In both patients with M. abscessus, the organism also grew in routine bacterial cultures. In one further patient, M. fortuitum was isolated from a sample not put into mycobacterial culture. To identify one new mycobacterial infection of bone or joint (MTBC or NTM) that would not be detected with routine bacterial cultures, 228 (95% CI 157 – 346) mycobacterial cultures were needed. The laboratory cost per additional patient identified using MGIT cultures was €12,540 (95% CI €8,635 - €19,030). Mycobacterial cultures were much less likely to be positive in samples taken from prosthetic joints. They were more likely to be positive in spinal samples and in samples taken from patients with suspected sarcoma. In patients for whom we had contemporaneous histological specimens, these demonstrated granulomatous inflammation in 86% (18/21) of patients from whom MTBC had been isolated but in neither of the two patients from whom only NTM was isolated. Ascertaining the clinical significance of NTM isolates is challenging, although in 2/8 cases the same organism was isolated following repeat sampling. Conclusions. Targeted rather than routine mycobacterial culture of bone and joint specimens should be considered in settings with a low burden of tuberculosis. NTM are rarely isolated from bone and joint specimens at our centre and fast growers may be isolated using routine bacterial culture

Aim. Dalbavancin is a lipoglycopeptide with a half-life of 14 days (range 6.1 to 18.4), significantly longer than other antimicrobials, which avoids the need for daily antibiotic dosing. This multi-centre observational study aims to describe the use of dalbavancin to facilitate discharge in treating bone and joint infections. Method. All adult patients treated with dalbavancin from January 2017 to September 2022 in four UK bone infection units were included. Data collected through a standardised data collection form included:. Clinical and microbiological characteristics. Hospital length of stay. Complications. Patient suitability for hypothetical treatment options, such as Outpatient Parenteral. Antibiotic Team (OPAT). Clinical outcome. Treatment-related costs were calculated for dalbavancin and the preferred hypothetical treatment option that would have been administered for the same duration. The costs were subtracted to calculate the cost difference. Clinical success was defined as the absence of definite failure in accordance with the OVIVA Trial protocol. Results. Thirty-six patients were included: 20 males and 16 females, with a median age of 53 (IQR 43–73): Thirteen were septic arthritis, twelve were prosthetic joints, seven were spondylodiscitis and five were other orthopaedic-related implant infections. In twenty cases the infecting organism was Staphylococcus aureus, fourteen were due to coagulase-negative staphylococci and two no cultured organism. Reasons for dalbavancin. The reasons for choosing dalbavancin over alternatives were due to either:. Necessity due to poor adherence (21), or lack of viable OPAT options due to antibiotic resistance or intolerance (7). OR. Convenience to avoid the need for OPAT (8). Dalbavancin was initiated at 1500mg after a median of 12 days (IQR 6–17) of in-hospital antimicrobial therapy. Subsequent dalbavancin doses were based on clinical decisions and ranged from 1000mg to 1500mg. Healthcare benefits. Switching to dalbavancin reduced treatment costs by a median of £3526 (IQR 1118 - 6251) compared with the preferred theoretical alternatives. A median of 31 hospital days (IQR 23–47) was avoided among patients who would have required a prolonged inpatient stay. Outcome. Overall, 20 patients (55.6%) were successfully treated after a median follow-up of 8 months (IQR, 5.8 – 18.4). No patients developed an adverse drug reaction. Conclusions. Dalbavancin can safely facilitate outpatient treatment in patients with limited oral options and in whom OPAT is unsuitable. Dalbavancin is cost-effective compared with the alternative of an inpatient stay

Aim. Fungal periprosthetic joint infections are difficult to treat and often associated with a limited outcome for patients. Candida species account for approximately 90% of all fungal infections. In vivo biofilm models play major role to study biofilm development, morphology, and regulatory molecules for bacteria. However, in vivo modeling of biofilm-associated fungi models are very rare. Furthermore, due to ethical restrictions, mammalian models are replaced with other alternative models in basic research. Recently, we have developed insect infection model G. mellonella larvae to study implant associated biofilm infections with bacteria. This model organism was not used for fungi biofilm infection yet. Thus, we aimed to establish G. mellonella as in vivo model to study fungal implant infections using Candida albicans as model organism and to test anti-fungal medication. Method. Titanium and Stainless steel K-wires were cut into small pieces with size of 4mm. For the infection process, implants were pre-incubated in specified fungal growth culture Candida albicans at 1×10. 7. CFU/ml for 30 min at 150 rpm shaking conditions. Later, these implants were washed with 10ml PBS and implanted in the larvae as mentioned. To analyze the susceptibility of the implant-associated fungal infections towards anti fungal compounds, the larvae were treated with amphotericin B, fluconazole and voriconazole after 24h of implantation. The effect of anti-fungal compounds was measured in terms of survival observation for 5 days and fungal load in larvae on 2. nd. day. To reveal the fungal biofilm formation on implant, the implants were removed on day 3 and processed for SEM analysis. Results. Pre-incubated K-wire caused the Candida infection and observed the death of the larvae. The treatment with antifungal compounds recovered the larvae from the implant-infection, except in case of Voriconazole. However, the recovery with treatment of anti fungal compounds was not effective as the larvae with planktonic infection, which highlights typical biofilm phenotype. Further, the treatment with anti-fungal compounds with Amphotericin B and Fluconazole reduced the fungal load in larvae tissue. The SEM analysis revealed the formation fungal biofilm with hyphae and spores associated with larvae tissue on implant surface. Conclusions. The results from survival analysis, antifungal treatment and SEM analysis are very promising to use of G. mellonella as in vivo model to study fungal infections on implanted materials. Our study highlights the use of G. mellonella larvae as alternative in vivo model to study implant-associated fungal infections that reduces the use of the higher mammals

Aims. The aims of this study were to report the efficacy of revision surgery for patients with co-infective bacterial and fungal prosthetic joint infections (PJIs) presenting to a single institution, and to identify prognostic factors that would guide management. Patients and Methods. A total of 1189 patients with a PJI were managed in our bone infection service between 2006 and 2015; 22 (1.85%) with co-infective bacterial and fungal PJI were included in the study. There were nine women and 13 men, with a mean age at the time of diagnosis of 64.5 years (47 to 83). Their mean BMI was 30.9 kg/m. 2. (24 to 42). We retrospectively reviewed the outcomes of these PJIs, after eight total hip arthroplasties and 14 total knee arthroplasties. The mean clinical follow-up was 4.1 years (1.4 to 8.8). Results. The median number of risk factors for PJI was 5.5 (interquartile range (IQR) 3.25 to 7.25). All seven patients who initially underwent debridement and implant retention (DAIR) had a recurrent infection that led to a staged revision. All 22 patients underwent the first of a two-stage revision. None of the nine patients with negative tissue cultures at the second stage had a recurrent infection. The rate of recurrent infection was significantly higher in the presence of multidrug-resistant bacteria (p = 0.007), a higher C-reactive protein (CRP) at the time of presentation (p = 0.032), and a higher number of co-infective bacterial organisms (p = 0.041). The overall rate of eradication of infection after two and five years was 50% (95% confidence interval (CI) 32.9 to 75.9) and 38.9% (95% CI 22.6 to 67), respectively. Conclusion. The risk of failure to eradicate infection with the requirement of amputation associated with this diagnosis is much higher than in patients with PJI without bacterial and fungal co-infection, and this risk is heightened when the fungal organism is joined by polymicrobial and multidrug-resistant bacterial organisms. Cite this article: Bone Joint J 2019;101-B:582–588

Aim. Microbial identification in the setting of periprosthetic joint infections (PJI) is crucial to tailor the best combination of surgical and medical treatment. Given the high cost, low sensitivity and slow results associated with traditional cultures, s synovial fluid antibody assay was developed. We asked whether antibody testing may be used as a proxy to traditional culture in the setting of PJI. Method. A retrospective study of patients who underwent revision total hip (THA) and knee (TKA) arthroplasty between January 2019 and January 2020 was performed. All patients were aspirated prior to revision surgery and antibody testing was performed. All patients had samples harvested for culture as per standard of care. Results of the two tests and their concordance when an organism was identified were compared. A frequency table was used and a McNemar test was used to compare the two methods. Results. 419 patients were included in this study. Antibody testing had a sensitivity and specificity of 21.9% and 92.5%, respectively, compared to traditional cultures. There were 78.1% of false negative and 7.5% of false positives (McNemar test p<0.001). Of the 12 patients who had positive results in both tests, 5 (41.7%) had discordant pathogens identified in each test. Conclusions. Synovial fluid antibody testing performed poorly when used as a substitute for cultures and may not be a clinically adequate surrogate despite lower cost and faster results. Not only was there a low sensitivity, but also a high rate of discordant organisms between the two tests when both were positive

Introduction. Despite recent advances in the diagnosis of periprosthetic joint infection(PJI), identifying the infecting organism continues to be a challenge, with up to a third of PJIs reported to have negative cultures. Current molecular techniques have thus far been unable to replace culture as the gold standard for isolation of the infecting pathogen. Next- generation sequencing(NGS) is a well-established technique for comprehensively sequencing the entire pathogen DNA in a given sample and has recently gained much attention in many fields of medicine. Our aim was to evaluate the ability of NGS in identifying the causative organism(s) in patients with PJI. Methods. After obtaining Institutional Review Board approval and informed consent for all study participants, samples were prospectively collected from 148 revision total joint arthroplasty procedures (83 knees, 65 hips). Synovial fluid, deep tissue and swabs were obtained at the time of surgery and shipped to the laboratory for NGS analysis (MicroGenDx). Deep tissue specimens were also sent to the institutional laboratory(Thomas Jefferson University Hospital) for culture. PJI was diagnosed using the Musculoskeletal Infection Society(MSIS) definition of PJI. Statistical analysis was performed using SPSS software. Results. Fifty-five revisions were considered infected; culture was positive in 40 of these (40/55, 72.7%), while NGS was positive in 47 (47/55, 85.5%). Among the positive cultures, complete concordance between NGS and culture was observed in 33 cases (33/40, 82.5%). One case was partially discordant between NGS and culture, with culture detecting three organisms as opposed to one organism on NGS. One case showed complete discordance with NGS and culture detecting different organisms. Three patients with negative NGS results had positive cultures. In another two cases culture simply reported the gross morphology of the organism but the phenotype was not identified, while NGS was able to definitively identify an organism. Among the 15 cases of culture-negative PJI, NGS was able to identify an organism in 10 cases (10/15, 66.7%). These data are summarized in Figure 1. Ninety-three revisions were considered to be aseptic; NGS exclusively identified microbes in 15 of 93 “aseptic” revisions (16.1%) and culture exclusively isolated an organism in 4 of 93 cases(5.3%). One case was positive on both NGS and culture, however the results were discordant from each other. The remaining cases (73/93, 78.5%) were both NGS and culture negative. NGS detected several organisms in most positive samples, with a greater number of organisms detected in aseptic compared to septic cases (6.8 vs. 4.0, respectively). Discussion. NGS was able to detect a pathogen in two-thirds of culture-negative cases and demonstrated a high rate of concordance with culture in culture-positive cases. The rate of false positives was low compared to earlier studies using molecular techniques. Our findings also suggest that some cases of PJI may be polymicrobial and escape detection using conventional culture. NGS may be a useful adjunct for identifying the causative organism(s) in PJI, particularly in the setting of negative cultures. Further study is required to determine the significance of isolated organisms in samples from patients who are not thought to be infected

Aim. While metagenomic (microbial DNA) sequencing technologies can detect the presence of microbes in a clinical sample, it is unknown whether this signal represents dead or live organisms. Metatranscriptomics (sequencing of RNA) offers the potential to detect transcriptionally “active” organisms within a microbial community, and map expressed genes to functional pathways of interest (e.g. antibiotic resistance). We used this approach to evaluate the utility of metatrancriptomics to diagnose PJI and predict antibiotic resistance. Method. In this prospective study, samples were collected from 20 patients undergoing revision TJA (10 aseptic and 10 infected) and 10 primary TJA. Synovial fluid and peripheral blood samples were obtained at the time of surgery, as well as negative field controls (skin swabs, air swabs, sterile water). All samples were shipped to the laboratory for metatranscriptomic analysis. Following microbial RNA extraction and host analyte subtraction, metatranscriptomic sequencing was performed. Bioinformatic analyses were implemented prior to mapping against curated microbial sequence databases– to generate taxonomic expression profiles. Principle Coordinates Analysis (PCoA) and Partial Least Squares-Discriminant Analysis were utilized to ordinate metatranscriptomic profiles, using the 2018 definition of PJI as the gold-standard. Results. After RNA metatranscriptomic analysis, blinded PCoA modeling revealed accurate and distinct clustering of samples into 3 separate cohorts (infected, aseptic, and primary joints) – based on their active transcriptomic profile, both in synovial fluid and blood (synovial anosim p=0.001; blood anosim p=0.034). Differential metatranscriptomic signatures for infected versus noninfected cohorts enabled us to train machine learning algorithms to 84.9% predictive accuracy for infection. Multiple antibiotic resistance genes were expressed, with high concordance to conventional antibiotic sensitivity data. Conclusions. Our findings highlight the potential of metatranscriptomics for infection diagnosis. To our knowledge, this is the first report of RNA sequencing in the orthopaedic literature. Further work in larger patient cohorts will better inform deep learning approaches to improve accuracy, predictive power, and clinical utility of this technology

Aim. Diagnosis and isolation of a causative organism is imperative for successful treatment of periprosthetic joint infections (PJI). While there are several diagnostic algorithms using microbiology, serum and synovial markers, the preoperative diagnosis of a low-grade infection remains a challenge, particularly in patients with unsuccessful aspiration. An incisional biopsy may be used in these cases as additional diagnostic tool. In this retrospective study we evaluated microbiological findings, sensitivity, and specificity of open synovial biopsies in cases of inconclusive preoperative diagnostics. Methods. In a retrospective databank analysis (2010–2018), we identified 80 TKAs that underwent an open biopsy because of inconclusive results after applying the CDC Criteria (2010) or the MSIS (2011–2018) for PJI. Infection makers in the serum (C-reactive protein [CRP], leucocytes count and interleukin-6 [IL-6]) and in the synovial aspirate (leucocyte count, percentage of neutrophiles) prior to the biopsy were analyzed. All biopsies were performed by suprapatellar mini-arthrotomy. If a subsequent revision surgery was performed, the isolated organisms in the open biopsy were compared to the results in the revision surgery and sensitivity and specificity were calculated. Serum markers were checked for correlation with a positive result in the open biopsy using Cramer-V and Chi. 2. -Test. Results. A positive result in the open biopsy occurred in 32 cases (40%) while 48 cases (60%) showed no growth of microorganisms. A preoperative elevated serum CRP (≥1mg/dl) showed a significant correlation for a positive biopsy (p=0.04). The odds ratio for a positive biopsy was 2.57 (95% CI 1.02–6.46) with elevated serum CRP. A revision surgery of the TKA with additional tissue sampling was performed in 27 (84%) cases with a positive biopsy and in 32 (67%) cases with a negative biopsy. The intraoperative tissue samples from the revision surgery showed microbial growth in only 52% of cases that were believed to be culture positive from the biopsy results, while positive cultures occurred in 41% of the cases with an initially negative biopsy. Patients with ≥ two cultures of the same microorganism in the biopsy presented a positive result in 73% of their revision surgeries. The open biopsy showed a sensitivity of 48% with a specificity of 62% in our collective if revision surgery was performed. Conclusion. Open biopsy may be considered with inconclusive preoperative serum and synovial fluid diagnostics for PJI, but sensitivity and specificity were rather low in this special collective. Further studies with bigger collectives should be performed to determine potential markers with a higher sensitivity

Periprosthetic joint infection (PJI) remains an extremely challenging complication. We have focused on this issue more over the last decade than previously, but there are still many unanswered questions. We now have a workable definition that everyone should align to, but we need to continue to focus on identifying the organisms involved. Surgical strategies are evolving and care is becoming more patient-centred. There are some good studies under way. There are, however, still numerous problems to resolve, and the challenge of PJI remains a major one for the orthopaedic community. This annotation provides some up-to-date thoughts about where we are, and the way forward. There is still scope for plenty of research in this area. Cite this article: Bone Joint J 2022;104-B(11):1193–1195

Gram-negative organisms are increasingly seen as causative pathogens in orthopaedic fracture surgery, which might necessitate a change in antibiotic prophylaxis protocols. A single-centre retrospective review of antibiogram results from all patients treated for fracture-related infection (FRI) was conducted. Subgroup analysis was undertaken to identify any host, injury or treatment variables predisposed to Gram-negative infection. The bacteriological results of 267 patients who underwent surgical treatment for FRI were analysed. Pathogens were isolated in 216 cases (81%), of which 118 (55%) were Gram-negative infections. Fractures involving the tibia and femur (p=0.007), the presence of soft tissue defect (p=0.003) and bone defects (p=0.001) were associated with an increased risk of developing a Gram- negative FRI. Gram-negative fracture-related infections were associated with injuries experiencing bone loss and those requiring soft tissue reconstruction. It is, therefore, prudent to consider extended Gram-negative directed antimicrobial prophylaxis in these cases to prevent the development of fracture-related infection

Background. Recent reports demonstrate that Next Generation Sequencing (NGS) facilitates pathogen identification in the context of culture-negative PJI; however the clinical relevance of the polymicrobial genomic signal often generated remains unknown. This study was conceived to explore: (1) the ability of NGS to identify pathogens in culture-negative PJI; and (2) determine whether organisms detected by NGS, as part of a prospective observational study, had any role in later failure of patients undergoing surgical treatment for PJI. Methods. In this prospective study samples were collected in 238 consecutive patients undergoing revision total hip and knee arthroplasties. Of these 83 patients (34.9%) had PJI, as determined using the Musculoskeletal Infection Society (MSIS) criteria, and of these 20 were culture-negative (CN-PJI). Synovial fluid, deep tissue and swabs were obtained at the time of surgery and sent for NGS and culture/MALDI-TOF. Patients undergoing reimplantation were excluded. Treatment failure was assessed using the previously described Delphi criteria. In cases of re-operation, organisms present were confirmed by culture and MALDI-TOF. Concordance of the infecting pathogen(s) at failure with the NGS analysis at the initial stage CN- PJI procedure was determined. Results. Twenty cases of culture-negative PJI were identified (Figure 1). CNPJI rate in our samples was 24%. NGS was positive in 18 cases. Two cases were both culture and NGS negative. Eight CN-PJIs (8/20; 40%) failed by re-operation with infection recurrence confirmed on culture. In 7 of these 8 cases (88%), the organism at failure was present on NGS at the time of the initial CN-PJI procedure. The remaining case failed with a new organism, via likely hematogenous seeding from an inter-current infection (Figure 2). NGS detected several organisms in CN-PJI cases (Figure 3). Discussion. CN-PJI is often associated with polymicrobial genomic organism profile. Furthermore, most of the failures by infection recurrence were due to an organism previously detected by NGS. Our findings suggest some cases of PJI may be polymicrobial and escape detection using conventional culture. Further multi-institutional work with larger numbers and longer clinical follow-up is required for validation

Aims. The diagnosis of periprosthetic joint infection can be difficult due to the high rate of culture-negative infections. The aim of this study was to assess the use of next-generation sequencing for detecting organisms in synovial fluid. Materials and Methods. In this prospective, single-blinded study, 86 anonymized samples of synovial fluid were obtained from patients undergoing aspiration of the hip or knee as part of the investigation of a periprosthetic infection. A panel of synovial fluid tests, including levels of C-reactive protein, human neutrophil elastase, total neutrophil count, alpha-defensin, and culture were performed prior to next-generation sequencing. Results. Of these 86 samples, 30 were alpha-defensin-positive and culture-positive (Group I), 24 were alpha-defensin-positive and culture-negative (Group II) and 32 were alpha-defensin-negative and culture-negative (Group III). Next-generation sequencing was concordant with 25 results for Group I. In four of these, it detected antibiotic resistant bacteria whereas culture did not. In another four samples with relatively low levels of inflammatory biomarkers, culture was positive but next-generation sequencing was negative. A total of ten samples had a positive next-generation sequencing result and a negative culture. In five of these, alpha-defensin was positive and the levels of inflammatory markers were high. In the other five, alpha-defensin was negative and the levels of inflammatory markers were low. While next-generation sequencing detected several organisms in each sample, in most samples with a higher probability of infection, there was a predominant organism present, while in those presumed not to be infected, many organisms were identified with no predominant organism. Conclusion. Pathogens causing periprosthetic infection in both culture-positive and culture-negative samples of synovial fluid could be identified by next-generation sequencing. Cite this article: Bone Joint J 2018;100-B:127–33

Aims. Arthrodesis is rarely used as a salvage procedure for patients with a chronically infected total knee arthroplasty (TKA), and little information is available about the outcome. The aim of this study was to assess the reliability, durability, and safety of this procedure as the definitive treatment for complex, chronically infected TKA, in a current series of patients. Methods. We retrospectively identified 41 patients (41 TKAs) with a complex infected TKA, who were treated between 2002 and 2016 using a deliberate, two-stage knee arthrodesis. Their mean age was 64 years (34 to 88) and their mean body mass index (BMI) was 39 kg/m. 2. (25 to 79). The mean follow-up was four years (2 to 9). The extensor mechanism (EM) was deficient in 27 patients (66%) and flap cover was required in 14 (34%). Most patients were host grade B (56%) or C (29%), and limb grade 3 (71%), according to the classification of McPherson et al. A total of 12 patients (29%) had polymicrobial infections and 20 (49%) had multi-drug resistant organisms; fixation involved an intramedullary nail in 25 (61%), an external fixator in ten (24%), and dual plates in six (15%). Results. Survivorship free from amputation, persistent infection, and reoperation, other than removal of an external fixator, at five years was 95% (95% confidence interval (CI) 89% to 100%), 85% (95% CI 75% to 95%), and 64% (95% CI 46% to 82%), respectively. Reoperation, other than removal of an external fixator, occurred in 13 patients (32%). After the initial treatment, radiological nonunion developed in ten knees (24%). Nonunion was significantly correlated with persistent infection (p = 0.006) and external fixation (p = 0.005). Of those patients who achieved limb salvage, 34 (87%) remained mobile and 31 (79%) had ‘absent’ or ‘minimal’ pain ratings. Conclusion. Knee arthrodesis using a two-stage protocol achieved a survivorship free from amputation for persistent infection of 95% at five years with 87% of patients were mobile at final follow-up. However, early reoperation was common (32%). This is not surprising as this series included worst-case infected TKAs in which two-thirds of the patients had a disrupted EM, one-third required flap cover, and most had polymicrobial or multi-drug resistant organisms. Cite this article: Bone Joint J 2020;102-B(6 Supple A):170–175

The aim of this investigation is to firstly quantify the burden of disease, and secondly qualify the organisms being cultured during debridement to establish their sensitivities to available antibiotics. This study will also look at the concomitant burden of Human Immunodeficiency Virus (HIV) and Diabetes Mellitus (DM) in cases of hand sepsis, to establish whether these two disease processes require special consideration and treatment tailoring. The method employed to collect the data will be retrospective collection of patient information, using random sampling. Included patients will be adult patients who undergo debridement and have a sample registered on the National Health Laboratory System (NHLS). The daily intake sheet will be used to collect patients details and these details will then be used to collect results of intra-operative specimens using the NHLS. These patient details will also be used to check patients’ HIV results and HBA1c (Glycated Haemoglobin A1c) results. Majority of the specimens revealed Methicillin Sensitive Staphylococcus Aureus (MSSA), with a reassuringly low rate of Methicillin Resistant Staphylococcus Aureus (MRSA) when compared to international data. The yield of patients tested for HIV or DM was lower than expected, despite this being the standard of care. The projected impact of this study will be assessment of the current burden of disease and then clarification of our current management strategy, in order to assess if it would be possible to change to a more cost-effective antibiotic with a narrower spectrum of bacteria coverage. The potential exists to not only implement cost saving measures, but also promote antibiotic stewardship by decreasing the practice of empiric broad-spectrum antibiotic use

Aim. Management of infection after osteosynthesis (IAO) poses a significant challenge in the setting of multidrug resistant organisms (MDRo). We have analysed whether IAO with MDRo has an adverse outcome. Method. We have retrospectively analysed patients with IAO from January 2001 to November 2016 with a minimum follow up of 12 months after the discontinuation of antibiotics. Results. 62 patients with a mean age of 49.76 years presenting a mean 135 days after onset of infection. 40 of them had associated comorbidities, commonest being diabetes mellitus. Majority of the patients were on empirical antibiotics prior to presentation. Deep cultures taken after implant removal in all cases at our institute grew 77 organisms {25 Gram positive (Gm+), 52 Gram negative (Gm-)}, commonest being pseudomonas aeruginosa (n=32). 12 patients had a mixed Gm+ and Gm- infections. 41/ 77 organisms cultured were multi-drug resistant (MDR) (Table 1). Infection remission was achieved in 56 patients (90.3%) at a mean follow up of 42.2 months, with 1 persistent infection, 2 amputations and 3 deaths. Union was achieved in 47/51 non unions. Conclusions. Radical debridement beyond infection with removal of implants, complemented by targeted local and systemic antibiotics along with a good soft tissue cover, surgical stabilization and bone grafting as needed can help achieve good results in spite of MDR organisms. For any figures or tables, please contact the authors directly

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

Infections in spine surgery are relatively common and devastating complications, a significant burden to the patient and the healthcare system. Usually, the treatment of SSIs consists of aggressive and prolonged antibiotic therapy, multiple debridements, and in chronic cases, hardware removal. Infections are correlated with worse subjective outcomes and even higher mortality. Depending on the type of spine surgery, the infection rate has been reported to be as higher as 20%. Recently silver-coated implants have been introduced in spine surgery to reduce the incidence of post-operative infections and to improve implant survivorship. The aim of the present study is to evaluate complications and outcomes in patients treated with silver-coated implants because of spine infection. All consecutive patients who had spine stabilization with a silver-coated implant from 2018 to 2021 were screened for inclusion in the study. Inclusion criteria were: (1) six months of minimum follow-up; (2) previous surgical site infection; hematogenous spondylodiscitis requiring surgical stabilization. Demographic and surgical information were obtained via chart review, all the device-related complications and the reoperation rate were also reported. A total of 57 patients were included in the present study. The mean age was 63.4 years, and there were 36 (63%) males and 21 (37%) females. Among the included cases, 57% were SSIs, 33% were spondylodiscitis, and 9% were hardware mobilization. Comorbidities such as diabetes mellitus, obesity, smoke, and oncological history were significant risk factors. In addition, the organisms cultured were Staphylococcus species in most of the cases. At six months of follow-up, 40% of patients were considered free from infection, while 20% needed multiple surgeries. The present research showed satisfactory results of silver-coated implants for the treatment of spine infection

Necrotizing soft tissue infection (NSTI) is a rapidly progressive infection that typically starts in the dermis and epidermis and spreads along soft tissue planes, penetrating subdermal layers and can lead to massive tissue necrosis resulting in severe morbidity and mortality. The aim of this case series was to describe the epidemiology and burden of NSTI's at a District Hospital servicing a South African urban settlement. This retrospective case series was performed at a single centre. Consecutive patients were identified following a clinical diagnosis for NSTI. Further laboratory pre-operative work up was standardized including: use of validated Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC scores) and Human Immunodeficiency Virus (HIV) status. All patients who underwent surgical debridement were captured on the Theatre Database (. www.medwebtools.org™. ). All patients received standardized perioperative, intra-operative and post-operative protocols for antibiotics, debridement and soft tissue closure or cover based on the severity of disease. Medical records, theatre notes, National Health Laboratory Service (NHLS) results and radiological results were captured for every patient. 28 patients (14 male, 14 female) presented with NSTI over a 3 year period (2021–2023). The mean age was 39.5 years. The most common organisms cultured were Streptococcus pyogenes (10 patients), Staphylococcus aureus (9 patients), Bacillus cereus (3 patients). This retrospective case series is an important study because it demonstrates some of the highest incidence of NSTI globally; however, the cause of this is yet to be determined. Our results show that having a high clinical index of suspicion; using the LRINEC score to assess severity and using a standardized antibiotic and peri-operative protocol with early soft tissue cover that NSTI's can be managed effectively with a reduction in patient morbidity and overall length of hospital stay

Surgical site infections following spinal surgery profoundly influence continued treatment, significantly impacting psychological and economic dimensions and clinical outcomes. Its reported incidence varies up to 20%, with the highest incidence amongst neuromuscular scoliosis and metastatic cord compression patients. We describe the first reported biphasic osteoconductive scaffold (Cerament G) with a logarithmic elution profile as a cumulative strategic treatment modality for adjacent spinal surgery infections. All patients who developed surgical site infections following instrumented fusion (May 2021-December 2021) had their demographics (age, sex), type and number of procedures, isolated organism, antibiotics given, comorbidities, and WHO performance status analysed. The infected wound was debrided to healthy planes, samples taken, and Cerament g applied. Thirteen patients were treated for deep SSI following spinal instrumentation and fusion procedures with intraoperative Cerament G application. There were four males and nine females with an average age of 40 ranging between 12 and 87. Nine patients underwent initial surgery for spinal deformity, and four were treated for fractures as index procedure. 77% of infections were attributable to MSSA and Cutibacteriousm acnes; others included Klebsiella, Pseudomonas and Streptococcus and targeted with multimodal cumulative therapy. A WHO performance score improved in 11 patients. In addition, there was no wound leak, and infection was eradicated successfully in 12/13 with a single procedure. This series shows the successful eradication of the infection and improved functional outcomes with Cerament G. However, the low numbers of patients in our series are an essential consideration for the broader applicability of this device

To determine risk factors of infection in total knee arthroplasty. This descriptive study was conducted in the Department of Orthopedics for a duration of three years from January 2016 to January 2019. All patients undergoing primary total knee replacement were included in the study. Exclusion criteria were all patients operated in another hospital and revision total knee replacement. All patients were followed up at 2, 4, 8, 12 and 24 weeks post-operatively. Signs of inflammation and inflammatory markers such as total leukocyte count (TLC), C-reactive protein (CRP) and ESR were measured. Risk factors like age, body mass index (BMI), ASA, co-morbid conditions were also noted. A total of 78 patients underwent primary unilateral Total Knee Replacement (TKR) during the study period. Of these, 30 (34.09%) were male and 48 (61.54%) female patients. Mean age of patients was 68.32 ± 8.54 years. Average BMI 25.89 Kg/m2 .Osteoarthritis was the pre-dominant cause of total knee replacement (94.87%). Among co-morbid factors 33.33% were diabetic, 28.20% having ischemic heart disease and 12.82% with chronic lung disease. Upon anaesthesia fitness pre-operatively, 91.02% patients had an American society of anaesthesiologist score (ASA) between 0–2 while 07 (8.97%) between 3- 5. Average duration of surgery was 85.62± 4.11 minutes. 6.41% cases got infected. In majority of the infected cases (60%), Staphylococcus aureus was the infective organism. Diabetes Mellitus (p=0.01) and Obesity (p=0.02) had a significant relation to post-operative infection. Pre-operative risk evaluation and prevention strategies along with early recognition of infection and control can greatly reduce the risk of joint infection post-TKR which will not only improve the mobility of patient but also its morbidity and mortality as well. Key Words:. C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), Staphylococcus aureus, Total Knee Arthroplasty (TKA)

Rates of prosthetic joint infection in megaprostheses are high. The application of silver ion coating to implants serves as a deterrent to infection and biofilm formation. A retrospective review was performed of all silver-coated MUTARS endoprosthetic reconstructions (SC-EPR) by a single Orthopaedic Oncology Surgeon. We examined the rate of component revision due to infection and the rate of infection successfully treated with antibiotic therapy. We reviewed overall revision rates, sub-categorised into the Henderson groupings for endoprosthesis modes of failure (Type 1 soft tissue failure, Type 2 aseptic loosening, Type 3 Structural failure, Type 4 Infection, Type 5 tumour progression). 283 silver-coated MUTARS endoprosthetic reconstructions were performed for 229 patients from October 2012 to July 2022. The average age at time of surgery was 58.9 years and 53% of our cohort were males. 154 (71.3%) patients underwent SC-EPR for oncological reconstruction and 32 (14.8%) for reconstruction for bone loss following prosthetic joint infection(s). Proximal femur SC-EPR (82) and distal femur (90) were the most common procedures. This cohort had an overall revision rate of 21.2% (60/283 cases). Component revisions were most commonly due to Type 4 infection (19 cases), Type 2 aseptic loosening/culture negative disease (15 cases), and Type 1 dislocation/soft tissue (12 cases). Component revision rate for infection was 6.7% (19 cases). 15 underwent exchange of implants and 4 underwent transfemoral amputation due to recalcitrant infection and failure of soft tissue coverage. This equates to a limb salvage rate of 98.3%. The most common causative organisms remain staphylococcus species (47%) and polymicrobial infections (40%). We expand on the existing literature advocating for the use of silver-coated endoprosthetic reconstructions. We provide insights from the vast experience of a single surgeon when addressing patients with oncological and bone loss-related complex reconstruction problems

Staphylococcus aureus is the most frequently isolated organism in periprosthetic joint infections. The mechanism by which synovial fluid (SF) kills bacteria has not yet been elucidated, and a better understanding of its antibacterial characteristics is needed. We sought to analyze the antimicrobial properties of exogenous copper in human SF against S. aureus. SF samples were collected from patients undergoing total elective knee or hip arthroplasty. Different S. aureus strains previously found to be sensitive and resistant, UAMS-1 and USA300 WT, respectively, were used. We performed in-vitro growth and viability assays to determine the capability of S. aureus to survive in SF with the addition of 10µM of copper. We determined the minimum bactericidal concentration of copper (MBC-Cu) and evaluated the sensitivity to killing, comparing WT and CopAZB-deficient USA300 strains. UAMS-1 evidenced a greater sensitivity to SF when compared to USA300 WT, at 12 (p=0.001) and 24 hours (p=0.027). UAMS-1 significantly died at 24 hours (p=0.017), and USA300 WT survived at 24 hours. UAMS-1 was more susceptible to the addition of copper at 4 (p=0.001), 12 (p=0.005) and 24-hours (p=0.006). We confirmed a high sensitivity to killing with the addition of exogenous copper on both strains at 4 (p=0.011), 12 (p=0.011), and 24 hours (p=0.011). Both WT and CopAZB-deficient USA300 strains significantly died in SF, evidencing a MBC-Cu of 50µM against USA300 WT (p=0.011). SF has antimicrobial properties against S. aureus, and UAMS-1 was more sensitive than USA300 WT. The addition of 10µM of copper was highly toxic for both strains, confirming its bactericidal effect. We evidenced CopAZB-proteins involvement in copper effluxion by demonstrating the high sensitivity of the mutant strain to lower copper concentrations. Thus, we propose CopAZB-proteins as potential targets and the use of exogenous copper as possible treatment alternatives against S. aureus

Platelet Rich Plasma (PRP), either rich (L-PRP) or poor (P-PRP) of leukocytes, is frequently used as an anti-inflammatory and regenerative tool in osteoarthritis (OA). PRP contains proteins but not genes as it is derived from megakaryocytes. Proteomics but not metabolomics of PRP was recently studied. Metabolomics is a field of ‘omics’ research involved in comprehensive portrayal of the small molecules, metabolites, in the metabolome. These small molecules can be endogenous metabolites or exogenous compounds found in an organism (1). Our aim was to determine the difference between L-PRP and P-PRP. A cross-sectional clinical study was designed in six recreational male athletes between the ages of 18 and 35 years. 3 mL P-PRP and 3 mL -LPRP was prepared from 60 mL of venous blood after treating with 9 mL of sodium citrate and centrifugation at 2.700 rpm for 10 min. Half of the prepared PRP's were frozen at −20°C for a week. Fresh and frozen samples were analyzed at the Q-TOF LC/MS device after thawing to room temperature. Untargeted metabolomic results revealed that the metabolomic profile of the L-PRP and P-PRP were significantly different from each other. A total of 33.438 peaks were found. Statistically significant (p<0.05) peaks were uploaded to the MetaboAnalyst 5.0 platform. Exogenous out of 2.308 metabolites were eliminated and metabolites found significant for our study were subjected to pathway analysis. Steroid biosynthesis, sphingolipid metabolism and metabolism of lipid pathways were affected. In the L-PRP samples, Nicotinamide riboside (FC: 2.2), MHPG (FC: 3.0), estrone sulfate (FC: 7.5), thiamine diphosphate (FC: 2.0), leukotriene E4 (FC: 7.5), PC(18:1 (9Z)e/2:0) (FC: 9.8) and Ap4A (FC: 2.1) were higher compared to P-PRP. C24 sulfatide (FC: −11.8), 3-hexaprenyl-4,5-dihydroxybenzoic acid (FC: −2.8) metabolites were furthermore lower in P-PRP. Clinical outcomes of PRP application should consider these metabolic pathways in future studies (2)

Aim. Antimicrobial resistance (AMR) aggravates an already difficult treatment of periprosthetic joint infections (PJI). The prevalence of drug-resistant pathogens varies across countries and increases over time. Regular monitoring of bacteriological analyses should be performed. Due to many factors influencing the AMR, the correct choice of antimicrobial management remains arguable. The primary purpose of this retrospective study was to identify and compare causative bacteria and to compare the incidence of antibiotic resistance between the septic revision total knee arthroplasty (TKA) and septic revision total hip arthroplasty (THA). Method. A review of all revision TKAs and revision THAs, undertaken between 2007 and 2020 in a tertiary referral centre, was performed. Included were cases meeting the consensus criteria for PJI, in which an organism has been identified. There were no major differences in tissue sampling between revision TKAs and revision THAs over time. Results. A total of 228 bacterial strains, isolated after revision TKA and THA, were analysed for their resistance to 20 different antibiotics. There was a statistically significant higher occurrence of Gram-negative bacteria (p=0.002) and Enterococcus species (p=0.026) identified after revision THAs compared to TKA. The comparison of antibiotic resistance between revision TKAs and revision THAs was statistically significant in 9 of 20 analysed antibiotics. Pathogens isolated after revision THA were much more resistant compared to pathogens isolated after revision TKA. Resistance in revision THAs was significantly higher to oxacillin (p=0.03), ciprofloxacin (p<0.001), levofloxacin (p<0.001), moxifloxacin (p=0.005), clindamycin (p<0.001), co-trimoxazole (p<0.001), imipenem (p=0.01), rifampicin (p=0.005) and tetracycline (p=0.009). There was no significantly higher resistance of pathogens isolated after revision TKAs detected. No statistically significant difference in antibiotic resistance of Gram-negative bacteria between revision TKA and revision THA was observed. Conclusions. The occurrence and the resistance of bacteria to antibiotics differs significantly between revision TKAs and revision THAs. This has implications on of the choice of empirical antibiotic in revision surgery as well as prophylactic antibiotic in primary surgery, depending on the joint that is to be replaced

Aim. Excision of chronic osteomyelitis (cOM) creates a dead space which must be managed to avoid early recurrence of infection. Systemic antimicrobials cannot penetrate this space in high concentration so local therapy has become an attractive adjunct to surgery. This study presents the mid- long-term results of local therapy with gentamicin in a bioabsorbable ceramic carrier. Method. A prospective series of 100 patients with Cierny & Mader Types III and IV cOM, affecting 105 bones, were treated with a single stage procedure, including debridement, deep tissue sampling, local and systemic antimicrobials, stabilization and immediate skin closure. cOM was confirmed with strict diagnostic criteria. Patients were followed up for a mean of 6.05 years (range 4.2–8.4 years). Results. At final follow-up, 6 patients had evidence of recurrent infection (94% infection-free). 3 infections recurred in the first year, with 2 in the second year and one at 4.5 years after surgery. Recurrence was not dependent on host physiological class (1/20 Class A; 5% vs 5/80 Class B; 6.25%. p=0.833). Nor was it related to aetiology of the infection, microbial culture or the presence of an infected non-union before surgery (1/10 with non-union; 10% vs 5/90 without non-union; 5.6%. p=0.57). Organisms which demonstrated intermediate or high-grade resistance to gentamicin were more likely in polymicrobial infections (9/21; 42.8%) compared to single isolate osteomyelitis (7/79; 8.9%)(p<0.001). However, recurrence was not more frequent when a resistant organism was present (1/16; 6.25% for resistant cases vs 5/84; 5.95% in sensitive culture infection) (p=0.96). Conclusions. This study shows that the single stage protocol, including a high delivery local antibiotic ceramic, was effective over several years. The method can be applied to a wide range of patients, including those with significant comorbidities and infected non-union

Literature debates whether fluid aspirates for suspected PJI should undergo prolonged incubation for cultures. We looked at sensitivity and specificity of 14-day cultures, compared to 7-days, for aspirates from prosthetic hips and knees. Design and methods. Conducted at a quaternary referral centre for PJIs from Jan 2017 to July 2019. Suspected PJIs who underwent aspiration, incubated 14 days and later surgical intervention with minimum three tissue samples were included. Results. 176 aspirates were included. This is an increased number compared to our historic figures (average 88 Vs 48 pts/yr). 47 patients had fluid and tissue positive (true positive), 20 fluid +ive but tissue -ive (false positive), 98 fluid and tissue -ive (true negative) and 15 fluid negative but tissue +ive (False negative). Thus, sensitivity 76%, specificity 83%, positive predictive value70% and negative predictive value 87%. Of 88 positive aspirates, only 75% were within 7-day cultures. Low virulence organisms as Propionibacterium acnes and coagulase negative staph were grown later. Of 48 with only one tissue sample positive, 38 were culture-negative on aspiration and 6 grew different organisms on aspirate and tissues. Also, as many were cultured later, it suggests contamination. Conclusion. Increased numbers reflect quaternary referral nature of institution and increasing PJI load. Modest drop in sensitivity and specificity of 14-day cultures compared to 7-day(84 and 85% respectively) is due to higher false negatives. Contamination contributes to false-ive as more tissue samples become positive (there were 1076 tissue samples due to multiple sampling Vs 176 aspirates). Higher tissue yield may also be because they are more representative. Effect of antibiotic use between samples cannot be determined. Organism profile suggest14-day culture produces more contaminant growth despite a well-equipped microbiology lab with laminar airflow for subcultures. Caution in interpreting 14-day results in diagnosis of PJI of Hip and Knee is advised

Aim. There is a lack of data supporting the use of doxycycline as a single agent after removing infected orthopaedic metalwork. We evaluated the efficacy and safety of doxycycline compared with other single antibiotic regimens used at our specialist orthopaedic hospital. Methods. A retrospective observational study including all adult patients diagnosed with an orthopaedic metalwork infection due to staphylococci. All patients were managed with the removal of metalwork, and multiple intraoperative samples were sent for culture, followed by the administration of at least four weeks of oral antibiotics. Antibiotic selection was on the recommendation of an infection consultant. Infection outcome was assessed as the proportion of patients meeting the OVIVA Trial definition of definite failure at follow-up. The probability of definite failure for doxycycline and the alternatives group was estimated using the Kaplan-Meier survival method. All adverse drug reactions (ADR) during treatment were analysed. Results. Seventy-nine orthopaedic metalwork infections were identified between July 2017 and July 2021. Forty-four were prosthetic joints, and 35 were fracture-related metalwork. In 54 cases, the infecting organism was Staphylococcus aureus, and 25 were due to coagulase-negative staphylococci. Forty-four were treated with doxycycline 100mg 12 hourly, and 35 were treated with alternatives (flucloxacillin 1g 6-hourly n=21 and clindamycin 450mg 6-hourly n=14). Overall, 70 patients (88.6%) were infection-free after a median follow-up of 23 months (IQR, 19 – 44). 38 (82.3%) were infection-free in the doxycycline group compared with 32 (91.4%) patients treated with alternatives. Of the failures in the alternatives group, all 3 received flucloxacillin. Survival analysis showed no significant difference in time to treatment failure between doxycycline and alternative antibiotics. Eighteen patients experienced an ADR: 2 nausea, one rash and one vaginal candidiasis due to doxycycline. Four diarrhoea, one reflux, two rashes and one headache due to clindamycin; 1 nausea and five diarrhoea due to flucloxacillin. Four patients required discontinuation therapy, two due to clindamycin and two due to flucloxacillin. Conclusions. In our cohort of patients, doxycycline monotherapy was an effective and well-tolerated oral option for treating staphylococcal infection following debridement and removal of orthopaedic metalwork

Two-stage exchange arthroplasty is traditionally used to treat periprosthetic hip infection. Nevertheless, particularly in high-risk patients, there has been increased attention towards alternatives such as 1.5-stage exchange arthroplasty which takes place in one surgery. Therefore, we sought to compare (1) operative time, length-of-stay (LOS), transfusions, (2) causative organism identification and polymicrobial infection rates, (3) re-revision rates and re-revision reasons, (4) mortality, and determine (5) independent predictors of re-revision. Retrospective chart review of 71 patients who underwent either 1.5- (n=38) or 2-stage (n=33) exchange hip arthroplasty at a single institution (03/2019-05/2023). Demographics, surgical, inpatient, and infection characteristics were noted. Main outcomes evaluated were re-revision rates, re-revision reasons, mortality, and cause of death. Independent predictors of re-revision were assessed utilizing logistic regression. Mean follow: 675 days (range, 23–1,715). Demographics were not significantly different except for a higher proportion of 1.5-stage patients classified as American-Society-of-Anesthesiologists (ASA) status 3 or 4 (84.2 vs. 48.5%, p=0.002). Length of follow-up was significantly longer in the 2-stage group (924.4 vs. 458 days, p<0.001) as well as operative time (506 vs. 271 minutes, p<0.001). In the 1.5-stage group, there was a higher proportion of polymicrobial infections (23.7 vs. 3.0%, p=0.016), re-revision rates (28.9 vs. 9.1%, p=0.042) and periprosthetic infections as a cause of revision (90.9 vs. 0%, p=0.007). Mortality rates were not significantly different, and no patient died for causes related to infection. Type of surgery (1.5-stage vs. 2-stage) was the only independent predictor of re-revision (odds-ratio 4.0, 95% confidence-interval 1.02–16.16, p=0.046). Our data suggests that patients who undergo 1.5-stage exchange arthroplasty have a significantly higher re-revision rate (mostly due to infection) when compared to 2-stage patients. We acknowledge potential benefits of the 1.5-stage strategy, especially in high-risk patients since it involves single surgery. However, higher re-revision rates must be considered when counseling patients

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

Aim. Fracture related infection (FRI) is classically defined as early (0–2 weeks), delayed (3–10 weeks) or late (>10 weeks). Treatment strategies reflect this, particularly with debridement and implant retention (DAIR), but there is little evidence to support this. This multinational study clarified the relationship between pathogens isolated and time from injury. Methods. All confirmed FRI cases, managed surgically, at three hospitals were included. Data were analyzed on patient demographics, time from injury and pathogens isolated. Patients who underwent DAIR were also analyzed separately. Results. 433 FRIs were studied, including 51 early cases (mean time from injury 1.6 weeks), 82 delayed cases (mean 5.5 weeks) and 300 late cases (mean 467.3 weeks, range 11-3432 weeks). 140 patients underwent DAIR (mean time since injury 56.8 weeks, range 0-946 weeks). Negative cultures were uncommon before 10 weeks but more frequent in late FRIs (4% vs 24%; p<0.0001). Over half of early and delayed FRIs were polymicrobial (59% and 56%) but only one quarter of late FRIs (26%; p=0.0004, p<0.0001). Cases treated with DAIR, at any time, had no difference in culture type (p=0.25). Staphylococcus aureus was the most frequent isolate. There was no significant difference in the range of bacterial species isolated in early, delayed or late infections (p=0.20) or in those patients who underwent DAIR (p=0.56). Conclusions. Bacterial species isolated in FRI do not change significantly over time. Up to 10 weeks, there was also no difference in the type of infection (polymicrobial, monomicrobial or culture negative). The increase in late culture negative FRIs may reflect more prolonged antibiotic use. Decisions on FRI treatment should not assume microbiological differences related to time from injury. We found no evidence of more virulent organisms in early infections with less virulent species presenting later. The clinical relevance of classifying FRI by time from injury remains unclear

The diagnosis of infection following shoulder arthroplasty is notoriously difficult. The prevalence of prosthetic shoulder infection after arthroplasty ranges from 3.9 – 15.4% and the most common infective organism is Cutibacterium acnes. Current preoperative diagnostic tests fail to provide a reliable means of diagnosis including WBC, ESR, CRP and joint aspiration. Fluoroscopic-guided percutaneous synovial biopsy (PSB) has previously been reported in the context of a pilot study and demonstrated promising results. The purpose of this study was to determine the diagnostic accuracy of percutaneous synovial biopsy compared with open culture results (gold standard). This was a multicenter prospective cohort study involving four sites and 98 patients who underwent revision shoulder arthroplasty. The cohort was 60% female with a mean age was 65 years (range 36-83 years). Enrollment occurred between June 2014 and November 2021. Pre-operative fluoroscopy-guided synovial biopsies were carried out by musculoskeletal radiologists prior to revision surgery. A minimum of five synovial capsular tissue biopsies were obtained from five separate regions in the shoulder. Revision shoulder arthroplasty was performed by fellowship-trained shoulder surgeons. Intraoperative tissue samples were taken from five regions of the joint capsule during revision surgery. Of 98 patients who underwent revision surgery, 71 patients underwent both the synovial biopsy and open biopsy at time of revision surgery. Nineteen percent had positive infection based on PSB, and 22% had confirmed culture positive infections based on intra-operative tissue sampling. The diagnostic accuracy of PSB compared with open biopsy results were as follows: sensitivity 0.37 (95%CI 0.13-0.61), specificity 0.81 (95%CI 0.7-0.91), positive predictive value 0.37 (95%CI 0.13 – 0.61), negative predictive value 0.81 (95%CI 0.70-0.91), positive likelihood ratio 1.98 and negative likelihood ratio 0.77. A patient with a positive pre-operative PSB undergoing revision surgery had an 37% probability of having true positive infection. A patient with a negative pre-operative PSB has an 81% chance of being infection-free. PSB appears to be of value mainly in ruling out the presence of peri-prosthetic infection. However, poor likelihood ratios suggest that other ancillary tests are required in the pre-operative workup of the potentially infected patient

Aim. Culture-based conventional methods are still the gold standard to identify microorganisms in hip and knee PJIs diagnosis. However, such approach presents some limitations due to prior antimicrobial treatment or the presence of unusual and fastidious organisms. Molecular techniques, in particular specific real-time and broad-range polymerase chain reaction (PCR), are available for diagnostic use in a suspected PJI. However, limited data is available on their sensitivity and specificity. This study aimed to evaluate the performance of a rapid and simple Investigational Use Only (IUO) version of the BioFire® JI multiplex PCR panel when compared to traditional microbiological procedures. Method. Fifty-eight native synovial fluid samples were recovered from 49 patients (female n=26; male =23) who underwent one or multiple septic or aseptic revision arthroplasties of the hip (n=12) and knee (n=46). The JI panel methodology was used either on specimens freshly collected (n=6) or stored at −80°C in our Musculoskeletal Biobank (n=52). The JI panel performance was evaluated by comparison with culture reference methods. Patient's medical records were retrieved from our institutional arthroplasty registry as well as our prospectively maintained PJI infection database. Results. The JI panel identified additional microorganisms in 3/39 (7.7%) positive cases, and a different microorganism in 1/39 (2.6%) sample. Out of 9/58 (15.5%) culture negative samples, two (22%) were positively detected by the JI panel. In total 49/58 (84%) native synovial fluid specimens were positive by culture methods, versus 39/58 (81.2%) with the JI panel. Ten samples are currently under investigation for confirmatory results. Out of 39 positive detections with the JI panel, 35 (89.7%) were concordant with the identified microorganism (n=29 same species; n=6 same genus). The combined information from the JI panel results and clinical records revealed the existence of 6/58 (10.3%) PJIs’ cases which would have required a different antibiotic therapeutic approach. Conclusions. The work presented, provides additional value for the clinical use of the JI panel to the improvement of PJI management in terms of rapid and successful treatment decisions, patient outcome, and healthcare costs. This technique shows high sensitivity to detect PJIs specific microorganisms in both fresh as well frozen native synovial fluid samples, thus emphasizing its use for retrospective studies analysis

Aim. metagenomic next-generation sequencing (mNGS) has shown to be a useful method for pathogen detection in prosthetic joint infections (PJI). The technique promises to minimize the PJIs without the known causative agent. Our study aimed to compare diagnostic accuracies of cultures and mNGS. Method. In this study, a meta-analysis following PRISMA recommendations was performed. PubMed and OVID Medline databases were used for article search. The studies using mNGS whole-genome sequencing method and the ones where PJI diagnosis was based on one of the currently recognized criteria were included. Studies were excluded if they comprised less than twenty cases, the ones with insufficient data for the analyses (true positive, true negative, false positive and false negative values for both mNGS and culture results) and publications with strong duplication bias. Univariate metanalysis using a random-effect model has been performed in R studio with a “meta” package. Pooled sensitivity and pooled specificity were calculated. Results. Seven studies with a total of 822 cases were included in the meta-analysis, 476 cases defined as PJI and 346 controls. Two studies used IDSA (Infectious Diseases Society of America) diagnostic criteria and the Illumina HiSeq 2500 platform for sequencing and five studies used MSIS (MusculoSkeletal Infection society). Four of those used the BGISEQ-500 sequencing platform. For one study there was no data available. Studies were performed on prosthetic hip and knee joints. Through meta-analysis, it was observed that mNGS technique is more sensitive than cultures with 90% (CI 79%– 95%) and 74% (CI 68%-79%) respectively (p=0.006). The specificity between methods was similar, for mNGS reaching 94% (CI 89%-96%) and for cultures 97% (CI 90%-99%) (p=0.285). In the PJI group, 117 new possible pathogens that were not isolated by microbiological culture were detected by the mNGS, most frequently anaerobes and coagulase-negative staphylococci both in 20/117 (17.1%) cases. Fourteen new organisms were detected in the control group and were mostly regarded as contaminants. Conclusions. Metagenomic sequencing has shown to be more sensitive than microbiological cultures in pathogen detection and thus has a great potential to improve the diagnosis and treatment of PJI. More studies on different prosthetic joints and comparing different diagnostic criteria for PJI would be needed to better understand the true diagnostic power of this method

Aims. Single-stage revision is not widely pursued due to restrictive inclusion criteria. In this study, we evaluated the results of single-stage revision of chronically infected total hip arthroplasty (THA) using broad inclusion criteria and cementless implants. Patients and Methods. Between 2010 and 2016, 126 patients underwent routine single-stage revision with cementless reconstruction with powdered vancomycin or imipenem poured into the medullary cavity and re-implantation of cementless components. For patients with a culture-negative hip, fungal infections, and multidrug-resistant organisms, a direct intra-articular infusion of pathogen-sensitive antibiotics was performed postoperatively. Recurrence of infection and clinical outcomes were evaluated. Three patients died and 12 patients (none with known recurrent infection) were lost to follow-up. There were 111 remaining patients (60 male, 51 female) with a mean age of 58.7 (. sd. 12.7; 20 to 79). Results. Of these 111 patients, 99 (89.2%) were free of infection at a mean follow-up time of 58 months (24 to 107). A recurrent infection was observed in four of the 23 patients (17.4%) with culture-negative infected hip. The success rate in patients with multidrug-resistant organisms was 84.2% (16/19). The mean postoperative Harris hip score was 79.6 points (63 to 92) at the most recent assessment. Conclusion. Routine single-stage revision with cementless reconstruction can be a viable option for the treatment of chronically infected THA. The results of this study will add to the growing body of evidence supporting routine use of single-stage revision for the treatment of chronically infected THA. Cite this article: Bone Joint J 2019;101-B:396–402

Aims. Use of molecular sequencing methods in periprosthetic joint infection (PJI) diagnosis and organism identification have gained popularity. Next-generation sequencing (NGS) is a potentially powerful tool that is now commercially available. The purpose of this study was to compare the diagnostic accuracy of NGS, polymerase chain reaction (PCR), conventional culture, the Musculoskeletal Infection Society (MSIS) criteria, and the recently proposed criteria by Parvizi et al in the diagnosis of PJI. Methods. In this retrospective study, aspirates or tissue samples were collected in 30 revision and 86 primary arthroplasties for routine diagnostic investigation for PJI and sent to the laboratory for NGS and PCR. Concordance along with statistical differences between diagnostic studies were calculated. Results. Using the MSIS criteria to diagnose PJI as the reference standard, the sensitivity and specificity of NGS were 60.9% and 89.9%, respectively, while culture resulted in sensitivity of 76.9% and specificity of 95.3%. PCR had a low sensitivity of 18.4%. There was no significant difference based on sample collection method (tissue swab or synovial fluid) (p = 0.760). There were 11 samples that were culture-positive and NGS-negative, of which eight met MSIS criteria for diagnosing infection. Conclusion. In our series, NGS did not provide superior sensitivity or specificity results compared to culture. PCR has little utility as a standalone test for PJI diagnosis with a sensitivity of only 18.4%. Currently, several laboratory tests for PJI diagnosis should be obtained along with the overall clinical picture to help guide decision-making for PJI treatment. Cite this article: Bone Joint J 2021;103-B(1):26–31

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

Aims. Metagenomic next-generation sequencing (mNGS) is useful in the diagnosis of infectious disease. However, while it is highly sensitive at identifying bacteria, it does not provide information on the sensitivity of the organisms to antibiotics. The purpose of this study was to determine whether the results of mNGS can be used to guide optimization of culture methods to improve the sensitivity of culture from intraoperative samples. Methods. Between July 2014 and October 2019, patients with suspected joint infection (JI) from whom synovial fluid (SF) was obtained preoperatively were enrolled. Preoperative aspirated SF was analyzed by conventional microbial culture and mNGS. In addition to samples taken for conventional microbial culture, some samples were taken for intraoperative culture to optimize the culture method according to the preoperative mNGS results. The demographic characteristics, medical history, laboratory examination, mNGS, and culture results of the patients were recorded, and the possibility of the optimized culture methods improving diagnostic efficiency was evaluated. Results. A total of 56 cases were included in this study. There were 35 cases of JI and 21 cases of non-joint infection (NJI). The sensitivity, specificity, and accuracy of intraoperative microbial culture after optimization of the culture method were 94.29%, 76.19%, and 87.5%, respectively, while those of the conventional microbial culture method were 60%, 80.95%, and 67.86%, respectively. Conclusion. Preoperative aspirated SF detected via mNGS can provide more aetiological information than preoperative culture, which can guide the optimization and improve the sensitivity of intraoperative culture. Cite this article: Bone Joint J 2021;103-B(1):39–45

Aim. Diagnosis of periprosthetic joint infection (PJI) presents a real challenge in some patients. Batteries of tests are available to reach this diagnosis. It is unknown if blood cultures have any role in diagnosis of PJI. The objective of this study was to evaluate whether blood cultures, taken in a group of patients with PJI, was useful in identifying the infecting pathogen. Methods. The institutional database was used to identify all patients treated at our institution between 2000 – 2015 for PJI according to the latest MSIS criteria. There were a total of 864 patients with mean age of 68 years. Synovial fluid sample and/or deep tissue samples were analyzed and cultured in all of these patients. In 371 (42.9%) patients with PJI, blood cultures were also taken. Statistical analyses were performed for correlation purposes. Results. In 246 (66.3%) patients in whom an organism was isolated from joint fluid, blood cultures were negative. 32 (8.6%) patients had both negative blood and synovial joint tissue culture. Of the 93 (25%) patients with positive blood cultures, 77 (82.7%) patients had identical organism in the joint and 16 (17.2%) had different organisms. Interestingly one infection that was fungal in nature showed no growth on tissue/fluid culture, yet a fungal organism was isolated in blood culture. Additionally, of the 93 patients with positive blood cultures, 57 (61.2%) had signs of systemic sepsis with leukocytosis and increased PMN/left shift. Within the 57 patients, 50 (87.7%) had identical blood and joint culture and 7 (12.2%) were from different culture organisms. 36 (38.7%) patients had subclinical infection with no signs of systemic sepsis. Discussion. Although this study does not advocate the routine use of blood culture for diagnosis of PJI, the finding that blood culture is successful in isolating the infecting organism as the joint in a handful of cases is compelling. Thus, the result of blood culture when performed should be considered as representative of the infecting organism in PJI cases

Infected total hip arthroplasty (THA) is catastrophic, but it is treatable with a high degree of success. Two-stage revision with an antibiotic-loaded cement spacer is the most widely accepted method of treatment, and considered by some to be the best method; however, single-stage treatment currently is used widely, and is gaining acceptance. Although antibiotic-loaded cement is considered to be important for antibiotic delivery after surgery, cementless revision is equally successful with one- or two-stage procedures. Delivery of antibiotics with depot methods, such as cement or bone graft impregnated with antibiotics, is considered to be effective, but the antibiotic levels rapidly deteriorate after the first three days, leaving the cement itself vulnerable to colonization by resistant organisms. Nephrotoxicity is not common, but it does occur, and necessitates removal of the cement. This can be catastrophic if the implants are fixed with antibiotic-impregnated cement. Success rates of THA revision for infection can be as high as 98%, but this rate is dependent on the organism. Failure rates of 20% are the norm for resistant organisms such as methicillin-resistant Staphylococcus aureus, The cost of this failure rate is huge. Failure probably is due to the low concentration of antibiotics in the operative site. Antibiotic infusion into the operative site achieves concentrations that are hundreds of times higher than can be achieved with any other technique and has the additional advantage of being able to be discontinued in the case of renal or auditory damage. Limited personal experience suggests that the failure rate of revision total hip with resistant organisms is significantly lower with intra-articular delivery than with other currently available methods. Between January 2002 and July 2013, 9 patients (9 hips) presented with late-onset acute infections in cementless THA with bone-ingrown implants. These patients were all more than 2 years from their original surgery and had acute symptoms of infection for 4 to 9 days. Two were the author's patients and 7 were referred from another institution. None had symptoms until the onset of their infection, and none had postoperative wound complications, fever, or prolonged pain suggestive of a chronic process. All were treated with debridement and head/liner exchange, followed by catheter infusion of intraarticular antibiotics. All remained free of signs of infection at a mean follow-up of 74 months (range, 62–121 months). This sequential series of successful treatment of late-onset infection of osteointegrated total hip replacement suggests that this is a highly effective method. It has the advantages of being a single-stage procedure, and of avoiding the catastrophic surgical procedure of removing fully osteointegrated total hip replacements

Next-generation sequencing (NGS) is a well-established technique for amplification and sequencing of DNA and has recently gained much attention in many fields of medicine. Our aim was to evaluate the ability of NGS in identifying the causative organism(s) in patients with periprosthetic joint infection (PJI). In this prospective study samples were collected from 78 revision total hip arthroplasties. Synovial fluid, deep tissue and swabs were obtained at the time of surgery and shipped to the laboratory for NGS analysis. Deep tissue specimens were also sent to the institutional lab for culture. PJI was diagnosed using the Musculoskeletal infection society (MSIS) definition of PJI. Thirty-four revisions were considered infected; culture was positive in 25 of these (25/34, 73.5%), while NGS was positive in 26 (26/34, 76.4%). Among the positive cultures, complete concordance between NGS and culture in 21 cases (21/25, 84.0%). 4 cases were discordant. Among these cases, 3 cases were culture-positive and NGS-negative, while 1 was both positive on NGS and culture for disparate organisms. Among the 9 cases of culture-negative PJI(CN-PJI), NGS was able to identify an organism in 4 cases (4/9, 44.4%). The remaining 5 cases were negative on both NGS and culture (5/9, 55.6%). Forty-four revisions were considered to be aseptic; NGS exclusively identified microbes in 7 of 44 “aseptic” revisions (15.9%) and culture exclusively isolated an organism in 3 of 44 cases (6.8%). Both NGS and culture were positive in 1 of case however the result was discordant. The remaining cases (33/44, 75.0%) were both NGS and culture negative. NGS detected several organisms in most positive samples, with a greater number of organisms detected in aseptic compared to septic cases (7 vs. 3.7, respectively). NGS may be a promising technique for identifying the infecting organism in PJI. Our findings suggest that some cases of PJI may be polymicrobial that escape detection using conventional culture

Periprosthetic joint infection (PJI) causes significant morbidity. Methicillin sensitive . Staphylococcus Aureus. (MSSA) is the most frequent organism, and the majority are endogenous. Nasal MSSA colonisation is a proven risk factor for S. aureus infection. Decolonisation reduces PJIs but there is a paucity of evidence comparing treatments. Aims; compare 3 nasal decolonisation treatments at (1) achieving MSSA decolonisation, (2) preventing PJI. Our hospital trust introduced MSSA screening and decolonisation prior to hip and knee arthroplasty in 2010. Data was prospectively collected since 2013, including all MSSA carriers, decolonisation treatment received, MSSA status at time of surgery and all PJIs. Prior to 2017 MSSA carriers received nasal mupirocin or neomycin, from August 2017 until August 2019 nasal octenidine was used. During the study period 15,958 primary hip and knee replacements were performed. 3,200 (20.1%) were MSSA positive at preoperative screening and received decolonisation treatment, 698 mupirocin, 1,210 neomycin and 1,221 octenidine. Mupirocin (89.1%) and neomycin (90.9%) were more effective at decolonisation than octenidine (50.0%, P<0.0001). There was no difference in S. aureus PJI rates (P=0.452). Of those negative at original screening 9.1% were positive on the day of surgery (1,164/12,758). MSSA decolonisation is an effective method to decrease PJI rates but there is little research into the best treatment. Both mupirocin and neomycin are more effective than octenidine at achieving MSSA decolonisation. There was poor correlation between the MSSA status after treatment and PJI rates. There is debate if treatment should be targeted by screening or if all patients she be treated without screening. Global decolonisation without screening is supported by the 26.7% of carriers that were negative at original screening in our study. Further research is needed comparing decolonisation treatments to reduce PJI rates and avoid the risk of drug resistance

Aim. To evaluate clinical outcomes for patients with osteomyelitis at a major trauma centre limb reconstruction unit. Method. We prospectively evaluated 137 patients on the limb reconstruction database with long bone osteomyelitis. Data on initial diagnosis, management (bone resection, use of external fixation, dead space and soft tissue management), microbiology and 2-year outcomes were collated. 11 patients' data was incomplete and 9 underwent primary amputations; these were excluded from microbiology data analysis. The patient data was categorised into microbiological culture negative or culture positive groups. Inter-group comparisons were made to evaluate two-year outcomes and percentage failure rate. Results. Forty percent (55/137) of patients presented with infected non-union, 20% (27/137) infected fractures, 19% (26/137) chronic osteomyelitis without implants and 14% (19/137) had infected metalwork. Removal of metalwork, reaming and debridement were the most frequently performed procedures, often in combination. 3% of patients failed treatment and had persistent infected non-union. The most common microorganisms identified in the culture positive group were Staphylococcus aureus (47.6%), Coagulase Negative Staphylococcus species (11.9%) and Enterobacter cloacae (11.9%), however multiple organism growth was more common than single organism growth, 53% and 47% respectively. 8% of culture negative patients had histological evidence of infection on biopsy. Conclusions. The 2-year failure rate (persistent infective non-union) was higher in the culture negative group (8%) than the culture positive group (1%). The higher failure rate may be secondary to lack of organisms isolated and available sensitivities from deep tissue samples. In 9 cases patient preference led to primary amputation over limb salvage procedures, without further infection. Our work highlights the array of factors contributing to outcome in this patient group. The incidence of micro-organisms commonly encountered in this cohort will provide further evidence to support choice of antibiotic for empirical therapy especially in cases which are culture negative. Finally, there are many challenges in achieving adequate outcomes in patients with long bone infections thus the need for a multidisciplinary team approach in this patient cohort is invaluable. Routine histology testing may be beneficial as this may highlight infective processes in culture negative patents thereby allowing optimization of patient management

Objectives. We wanted to investigate regional variations in the organisms reported to be causing peri-prosthetic infections and to report on prophylaxis regimens currently in use across England. Methods. Analysis of data routinely collected by Public Health England’s (PHE) national surgical site infection database on elective primary hip and knee arthroplasty procedures between April 2010 and March 2013 to investigate regional variations in causative organisms. A separate national survey of 145 hospital Trusts (groups of hospitals under local management) in England routinely performing primary hip and/or knee arthroplasty was carried out by standard email questionnaire. Results. Analysis of 189 858 elective primary hip and knee arthroplasty procedures and 1116 surgical site infections found statistically significant variations for some causative organism between regions. There was a 100% response rate to the prophylaxis questionnaire that showed substantial variation between individual trust guidelines. A number of regimens currently in use are inconsistent with the best available evidence. Conclusions. The approach towards antibiotic prophylaxis in elective arthroplasty nationwide reveals substantial variation without clear justification. Only seven causative organisms are responsible for 89% of infections affecting primary hip and knee arthroplasty, which cannot justify such widespread variation between prophylactic antibiotic policies. Cite this article: Bone Joint Res 2015;4:181–189

Introduction. Periprosthetic infection (PJI) after primary total knee arthroplasty (TKA) remains a challenging issue affecting 1–2% of cases. Locally delivered prophylactic antibiotics, including tobramycin or gentamicin mixed in polymethylmethacrylate (PMMA) bone cement and vancomycin powder, are increasingly used despite a lack of high quality evidence for either practice. In this study, we report the antibiotic susceptibility of organisms recovered in culture from patients with acute prosthetic joint infection after primary TKA to gentamicin, tobramycin and vancomycin. Methods. Using a retrospective database of all primary TKA performed at a single institution between January, 1 2014 and July 1, 2018, we identified 18 cases of acute PJI after primary TKA, as defined by the Musculoskeletal Infection Society 2011 guidelines as less than 3 months from symptoms or index surgery to presentation. The use of antibiotic bone cement during the index procedure and time to surgical management of the infection were recorded. Fluid cultures and tissue cultures were obtained intraoperatively at the time of revision. The organisms from positive cultures underwent MIC testing to gentamicin, tobramycin and vancomycin using a gradient diffusion method (ETEST). MIC breakpoints for susceptibility were based on Clinical and Laboratory Standards Institute definitions. Results. 18 cases of PJI after TKA were identified, including 4 polymicrobial infections (22.2%) (Table 1). Average time to revision for infection was 38 days (range: 6–84 days). 34.8% of bacterial isolates were resistant to gentamicin, 39.1% were resistant to tobramycin and 17.4% were resistant to vancomycin. Of the 8 bacterial isolates resistant to gentamicin, 7 (87.5%) were susceptible tobramycin. Of the 9 bacterial isolates resistant to tobramycin, (88.9%) were susceptible to vancomycin. One bacterial isolate, a Fusobacterium nucleatum from a polymicrobial infection was resistant to gentamicin, tobramycin and vancomycin. Conclusion. Over one third of bacteria causing acute PJI after primary TKA were resistant to the aminoglycosides pre-mixed in commercially available bone cements. All but one of the bacteria resistant to gentamicin and tobramycin were susceptible to vancomycin. The addition of vancomycin to bone cement or as powder in the surgical field has the potential to expand antibiotic coverage to include most organisms responsible for acute PJI after TKA. For figures, tables, or references, please contact authors directly

Aims. The aim of this study was to identify the incidence of positive cultures during the second stage of a two-stage revision arthroplasty and to analyse the association between positive cultures and an infection-free outcome. Patients and Methods. This single-centre retrospective review of prospectively collected data included patients with a periprosthetic joint infection (PJI) of either the hip or the knee between 2013 and 2015, who were treated using a standardised diagnostic and therapeutic algorithm with two-stage exchange. Failure of treatment was assessed according to a definition determined by a Delphi-based consensus. Logistic regression analysis was performed to assess the predictors of positive culture and risk factors for failure. The mean follow-up was 33 months (24 to 48). Results. A total of 163 two-stage revision arthroplasties involving 84 total hip arthroplasties (THAs) and 79 total knee arthroplasties (TKAs) were reviewed. In 27 patients (16.6%), ≥ 1 positive culture was identified at re-implantation and eight (29.6%) of these subsequently failed compared with 20 (14.7%) patients who were culture-negative. The same initially infecting organism was isolated at re-implantation in nine of 27 patients (33.3%). The organism causing re-infection in none of the patients was the same as that isolated at re-implantation. The risk of the failure of treatment was significantly higher in patients with a positive culture (odds ratio (OR) 1.7; 95% confidence interval (CI) 1.0 to 3.0; p = 0.049) and in patients with a higher Charlson Comorbidity Index (OR 1.5; 95% CI 1.6 to 1.8; p = 0.001). Conclusion. Positive culture at re-implantation was independently associated with subsequent failure. Surgeons need to be aware of this association and should consider the medical optimisation of patients with severe comorbidities both before and during treatment. Cite this article: Bone Joint J 2017;99-B:1490–5

Aim. Current guidelines for the diagnosis of prosthetic joint infection (PJI) recommend collecting 4–5 independent tissue specimens, with isolation of indistinguishable organisms from two or more specimens. The same principle has been applied to other orthopaedic device-related infections (DRI) including fracture-related infections. However there are few published data validating this approach in DRI other than PJI. We evaluated the performance of different diagnostic cutoffs and varying numbers of tissue specimens for microbiological sampling in fracture-related infections. Method. We used standard protocols for tissue sample collection and laboratory processing, and a standard clinical definition of fracture-related infection. We explored how tissue culture sensitivity and specificity varied with the number of tissue specimens obtained; and with the number of specimens from which an identical isolate was required (diagnostic cutoff). To model the effect of the number of specimens taken we randomly sampled n specimens from those obtained at each procedure, excluding procedures from which less than n specimens were collected, and calculated sensitivity and specificity based on this sample. For each value of n we repeated this process 100 times to estimate the mean sensitivity and specificity for n specimens. Results. We analysed data for 246 cases of suspected fracture-related infection. 77 (31%) met the clinical definition of infection. A median of 4 independent tissue samples were obtained from each procedure (IQR 4–5). Culture sensitivity was highest and specificity lowest using a diagnostic cutoff of 1 specimen for isolation of an organism; specificity increased at the expense of sensitivity with diagnostic cutoffs of 2 or 3 specimens. Culture sensitivity increased as the number of tissue specimens obtained increased from 1 to 4. Although there was a corresponding decline in specificity with increasing numbers of tissue specimens obtained, this was negligible when a diagnostic cutoff of 2 or 3 specimens with identical organisms was used. Using a cutoff of 2 specimens with identical organisms, obtaining 4 specimens gave a sensitivity of 68% (55–78%) and a specificity of 95% (86–99%). Small numbers prevented meaningful analysis of the diagnostic performance of five or more specimens. Conclusions. These data are analogous to findings in prosthetic joint infections, and suggest similar principles may be applied to tissue sampling and culture interpretation in other orthopaedic DRI including fracture-related infection. A larger study is underway to evaluate the performance of greater numbers of tissue specimens

Aim. As the populations of patients who have multiple prosthetic joints increase these years, the fate of a single joint periprosthetic joint infection in these patients is still unknown. Risk factors leading to a subsequent infection in another prosthetic joint are unclear. Our goal is to identify the risk factors of developing a subsequent infection in another prosthetic joint and describe the organism profile to the second prosthetic infection. Method. We performed a retrospective cohort study of all PJI cases underwent surgical intervention at our institute, a tertiary care referral center over 11 years, during January 2006 to December 2016. We identified 96 patients with periprosthetic joint infection who had another prosthetic joint in place at the time of presentation. The comorbidity, number of prosthetic joints, date and type of each arthroplasty, times of recurrent infection at each prosthetic joint with subsequent debridement or 2-stage resection arthroplasty, organisms from every infection episode, the outcome of each periprosthetic joint infection in these patients were analyzed. Results. During January 2006 to May 2017, we retrospective collected 294 PJI cases (159 hips, 135 knees) in our institute. Patients with single prosthetic joint were excluded and finally 96 patients were included. Of the 96 patients, 19 (19.79%) developed a periprosthetic joint infection in a second joint. The type of organism was the same as the first infection in 12 (63.16%) of 19 patients. The time to developing a second infection averaged 2.16 years (range, 0–9.3 years). The risk factors leading to a subsequent infection in another prosthetic joint are albumin level (< 3.5 mg/dl), long-term steroid usage (> 5mg/day, > 3 months), history of necrotizing fasciitis, history of invasive dental procedure (> Grade IV procedure), 3-stage resection arthroplasty or more, and PJI caused by vacomycin-resistent enterococcus (VRE). Conclusions. A PJI might predispose patients to subsequent PJI in another prosthesis. Patients and surgeons must be aware of the risk factors contribute to this devastating complication. Most organisms in the second PJI are identical to the first one, and we believe the bacteremia may be the pathogenesis, but need further proved. The preventive policy may be needed in the future for this population who has multiple prosthetic joints

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

Aims. The International Consensus Meeting on Musculoskeletal Infection (ICM, Philadelphia 2018) recommended histology as one of the diagnostic tests although this is not routinely used in a number of UK hospitals. This study aims to explore the role of histology in the diagnosis of infection and whether it is of practical use in those cases where the microbiology samples are either diagnostically unclear or do not correspond to the pre-operative diagnosis or the clinical picture. Patients and Methods. We identified 85 patients who underwent revision knee arthroplasty for either septic or aseptic loosening and for whom both microbiology and histology samples were taken. The procedures were performed by the senior experienced surgeons specialised in revision knee arthroplasty in two centres from Liverpool. Each patient had a minimum of five tissue samples taken, using separate knife and forceps and each sample was divided in half and sent for microbiology and histology in different containers. Fifty-four patients (63.5%) underwent a single-staged revision; ten patients (11.8%) underwent the 1. st. stage of a two staged revision; eleven patients (12.9%) underwent the 2. nd. stage of a two staged revision; one patient (1.2%) underwent an additional revision stage; three patients (3.5%) were treated with a DAIR; three patients (3.5%) had a 2-in-1 revision; two patients (2.4%) had a debridement and polyethylene exchange; and one patient (1.2%) had an arthroscopy biopsy of knee replacement. The cost to process five microbiology samples for each patient was £122.45 on average and for the five histology samples was £130. Results. In 63.5% (n=54) the histology and microbiology confirmed an aseptic joint as suspected beforehand. In 8.2% (n=7) the histology result was the same as the microbiology result confirming infection as suspected beforehand. In 15.3% (n=13) where asepsis was suspected beforehand, one of the five microbiology samples unexpectedly grew an organism but all the histological samples showed no evidence of infection. In these cases, the histology result supported the diagnosis of the likelihood of a contaminant. In 5.9% (n=5) we found differences in the microbiology and histology in one sample and in 7.1% (n=6) the histology was different to the microbiology in more than one sample. Conclusions. In cases where the diagnosis of sepsis within a knee replacement is not in doubt due to pre-operative microbiology, we found no benefit in additional histology sampling. In 28.3% of the cases, the histology was of use in the diagnosis of infection in complex cases and a useful tool in the decision process for further management. In over half of the cases where the revision was for aseptic loosening, the histology result did not alter the management but 28.3% of cases that were thought to be aseptic, microbiology revealed at least one positive sample hence the histology was of use in making a final diagnosis, be that of infection, contamination or to rule out infection. Whilst histology is of use in the latter groups but not the aseptic group, these outcomes are not predictable until after the post-operative period hence histology is required in all these cases. Overall, the histology is a cheap test which is of benefit in the diagnosis of complex peri-prosthetic joint infection in one–third of cases and we support the ICM recommendation

Aim. In vivo biofilm models play major role to study biofilm development, morphology, and regulatory molecules involve in biofilm. Due to ethical restrictions, the use mammalian models are replaced with other alternative models in basic research. Recently, we have developed insect infection model G. mellonella larvae to study implant associated biofilm infections. This model organism is easy to handle, cheap and ethical restriction free and could be used for the high through put screening of antimicrobial compounds to treat biofilm. To promote the use of this model in basic research we aimed to validate this based on the typical biofilm features such as less susceptible to the antibiotics, complexity of the biofilm structure and gene expression profile of biofilms. Method. G. mellonella larvae are maintained at 30oC on artificial diet in an incubator. Titanium and Stainless steel K-wires were cut into small pieces with size of 4mm. After sterilization with 100% alcohol, these K-wires were pre-incubated in S. aureus bacterial suspension (5×10. 6. CFU/ml) for 30 min, washed in PBS and implanted inside the larva after with help of scalpel. The larvae were incubated at 37. o. C for two day for the survival analysis. To analyze the less susceptibility of the biofilms towards antibiotics, the larvae were treated with gentamicin and compared survival with planktonic infection in G. mellonella. To reveal the complex structure of biofilm, the implants were removed and processed for the MALDI analysis. Whole genome-based transcriptome of biofilm was performed to explore the changes in transcriptional landscapes. Results. The results are very promising to validate the use of G. mellonella as in vivo model to study the biofilm formation on implanted materials. The gentamicin treatment could rescue the larvae from the planktonic infection, but not from the biofilm infection on the implants. Further, the MALDI analysis could reveal the complex structure and components of S. aureus biofilm formed on the implant inside the larvae. Finally, the transcriptomic analysis revealed the gene expression changes that can be compared to normal biofilm expression profile. Conclusions. Further, comparison of these results with other in vivo models such as rat and mouse as well as acute and chronic clinical samples from patients with implant-associated bone infections could validate and relevant use of this model to study S. aureus biofilm infections