Aims. Bacterial infection activates neutrophils to release neutrophil extracellular traps (NETs) in bacterial biofilms of periprosthetic joint infections (PJIs). The aim of this study was to evaluate the increase in NET activation and release (NETosis) and haemostasis markers in the plasma of patients with PJI, to evaluate whether such plasma induces the activation of neutrophils, to ascertain whether increased NETosis is also mediated by reduced DNaseI activity, to explore novel therapeutic interventions for NETosis in PJI in vitro, and to evaluate the potential diagnostic use of these markers. Methods. We prospectively recruited 107 patients in the preoperative period of prosthetic surgery, 71 with a suspicion of PJI and 36 who underwent arthroplasty for non-septic indications as controls, and obtained citrated plasma. PJI was confirmed in 50 patients. We measured NET markers, inflammation markers, DNaseI activity, haemostatic markers, and the thrombin generation test (TGT). We analyzed the ability of plasma from confirmed PJI and controls to induce NETosis and to degrade in vitro-generated NETs, and explored the therapeutic restoration of the impairment to degrade NETs of PJI plasma with recombinant human DNaseI. Finally, we assessed the contribution of these markers to the diagnosis of PJI. Results. Patients with confirmed PJI had significantly increased levels of NET markers (cfDNA (p < 0.001), calprotectin (p < 0.001), and neutrophil elastase (p = 0.022)) and inflammation markers (IL-6; p < 0.001) in plasma. Moreover, the plasma of patients with PJI induced significantly more neutrophil activation than the plasma of the controls (p < 0.001) independently of tumour necrosis factor alpha. Patients with PJI also had a reduced DNaseI activity in plasma (p < 0.001), leading to a significantly impaired degradation of NETs (p < 0.001). This could be therapeutically restored with recombinant human DNaseI to the level in the controls. We developed a model to improve the diagnosis of PJI with cfDNA, calprotectin, and the start tail of TGT as predictors, though cfDNA alone achieved a good prediction and is simpler to measure. Conclusion. We confirmed that patients with PJI have an increased level of NETosis in plasma. Their plasma both induced NET release and had an impaired ability to degrade NETs mediated by a reduced DNaseI activity. This can be therapeutically restored in vitro with the approved Dornase alfa, Pulmozyme, which may allow novel methods of treatment. A combination of NETs and haemostatic biomarkers could improve the diagnosis of PJI, especially those patients in whom this diagnosis is uncertain. Cite this article: Bone Joint J 2024;106-B(9):1021–1030

External fixation is widely used in orthopaedic and trauma surgery. Infections around pin or wire sites, which are usually localised, non-invasive, and are easily managed, are common. Occasionally, more serious invasive complications such as necrotising fasciitis (NF) and toxic shock syndrome (TSS) may occur. . We retrospectively reviewed all patients who underwent external fixation between 1997 and 2012 in our limb lengthening and reconstruction programme. A total of eight patients (seven female and one male) with a mean age of 20 years (5 to 45) in which pin/wire track infections became limb- or life-threatening were identified. Of these, four were due to TSS and four to NF. Their management is described. A satisfactory outcome was obtained with early diagnosis and aggressive medical and surgical treatment. . Clinicians caring for patients who have external fixation and in whom infection has developed should be aware of the possibility of these more serious complications. Early diagnosis and aggressive treatment are required in order to obtain a satisfactory outcome. Cite this article: Bone Joint J 2015;97-B:1296–1300

Aims. Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation. Methods. A mouse model of PJI of the knee was used. Mice were randomized into groups with intervention at the time of surgery (postoperative day (POD) 0): a sterile control (SC; n = 6); infected control (IC; n = 15); systemic vancomycin (SV; n = 9); vancomycin powder (VP; n = 21); and vancomycin bead (VB; n = 19) groups. Delayed inoculation was introduced during an arthrotomy on POD 7 with 1 × 10. 5. colony-forming units (CFUs) of a bioluminescent strain of Staphylococcus aureus. The bacterial burden was monitored using bioluminescence in vivo. All mice were killed on POD 21. Implants and soft-tissue were harvested and sonicated for analysis of the CFUs. Results. The mean in vivo bioluminescence in the VB group was significantly lower on POD 8 and POD 10 compared with the other groups. There was a significant 1.3-log. 10. (95%) and 1.5-log. 10. (97%) reduction in mean soft-tissue CFUs in the VB group compared with the VP and IC groups (3.6 × 10. 3. vs 7.0 × 10. 4. ; p = 0.022; 3.6 × 10. 3. vs 1.0 × 10. 5. ; p = 0.007, respectively) at POD 21. There was a significant 1.6-log. 10. (98%) reduction in mean implant CFUs in the VB group compared with the IC group (1.3 × 10. 0. vs 4.7 × 10. 1. , respectively; p = 0.038). Combined soft-tissue and implant infection was prevented in 10 of 19 mice (53%) in the VB group as opposed to 5 of 21 (24%) in the VP group, 3 of 15 (20%) in the IC group, and 0% in the SV group. Conclusion. In our in vivo mouse model, antibiotic-releasing calcium sulphate beads appeared to outperform vancomycin powder alone in lowering the bacterial burden and preventing soft-tissue and implant infections. Cite this article: Bone Joint J 2024;106-B(6):632–638

Aims. The aim of this study was to analyze the prevalence of culture-negative periprosthetic joint infections (PJIs) when adequate methods of culture are used, and to evaluate the outcome in patients who were treated with antibiotics for a culture-negative PJI compared with those in whom antibiotics were withheld. Methods. A multicentre observational study was undertaken: 1,553 acute and 1,556 chronic PJIs, diagnosed between 2013 and 2018, were retrospectively analyzed. Culture-negative PJIs were diagnosed according to the Muskuloskeletal Infection Society (MSIS), International Consensus Meeting (ICM), and European Bone and Joint Society (EBJIS) definitions. The primary outcome was recurrent infection, and the secondary outcome was removal of the prosthetic components for any indication, both during a follow-up period of two years. Results. None of the acute PJIs and 70 of the chronic PJIs (4.7%) were culture-negative; a total of 36 culture-negative PJIs (51%) were treated with antibiotics, particularly those with histological signs of infection. After two years of follow-up, no recurrent infections occurred in patients in whom antibiotics were withheld. The requirement for removal of the components for any indication during follow-up was not significantly different in those who received antibiotics compared with those in whom antibiotics were withheld (7.1% vs 2.9%; p = 0.431). Conclusion. When adequate methods of culture are used, the incidence of culture-negative PJIs is low. In patients with culture-negative PJI, antibiotic treatment can probably be withheld if there are no histological signs of infection. In all other patients, diagnostic efforts should be made to identify the causative microorganism by means of serology or molecular techniques. Cite this article: Bone Joint J 2022;104-B(1):183–188

Aims. Despite the COVID-19 pandemic, incidence of hip fracture has not changed. Evidence has shown increased mortality rates associated with COVID-19 infection. However, little is known about the outcomes of COVID-19 negative patients in a pandemic environment. In addition, the impact of vitamin D levels on mortality in COVID-19 hip fracture patients has yet to be determined. Methods. This multicentre observational study included 1,633 patients who sustained a hip fracture across nine hospital trusts in North West England. Data were collected for three months from March 2020 and for the same period in 2019. Patients were matched by Nottingham Hip Fracture Score (NHFS), hospital, and fracture type. We looked at the mortality outcomes of COVID-19 positive and COVID-19 negative patients sustaining a hip fracture. We also looked to see if vitamin D levels had an impact on mortality. Results. The demographics of the 2019 and 2020 groups were similar, with a slight increase in proportion of male patients in the 2020 group. The 30-day mortality was 35.6% in COVID-19 positive patients and 7.8% in the COVID-19 negative patients. There was a potential association of decreasing vitamin D levels and increasing mortality rates for COVID-19 positive patients although our findings did not reach statistical significance. Conclusion. In 2020 there was a significant increase in 30-day mortality rates of patients who were COVID-19 positive but not of patients who were COVID-19 negative. Low levels of vitamin D may be associated with high mortality rates in COVID-19 positive patients. Cite this article: Bone Joint J 2021;103-B(4):782–787

An extensive review of the spinal and arthroplasty literature was undertaken to evaluate the effectiveness of local antibiotic irrigation during surgery. The efficacy of antibiotic irrigation for the prevention of acute post-operative infection after total joint arthroplasty was evaluated retrospectively in 2293 arthroplasties (1990 patients) between January 2004 and December 2013. The mean follow-up was 73 months (20 to 139). One surgeon performed all the procedures with minimal post-operative infection. . The intra-operative protocol included an irrigation solution of normal saline with vancomycin 1000 mg/l and polymyxin 250 000 units/l at the rate of 2 l per hour. No patient required re-admission for primary infection or further antibiotic treatment. Two morbidly obese patients (two total hip arthroplasties) developed subcutaneous fat necrosis requiring debridement and one was revised because the deep capsular sutures were contaminated by the draining subcutaneous haematoma. One patient who had undergone total knee arthroplasty had unrecognised damage to the lateral superior geniculate artery and developed a haematoma that became infected secondarily four months after the surgery and underwent revision. . The use of antibiotic irrigation during arthroplasty surgery has been highly effective for the prevention of infection in the author’s practice. However, it should be understood that any routine prophylactic use of antibiotics may result in resistant organisms, and the wise stewardship of the use of antibiotics is an important part of surgical practice. Cite this article: Bone Joint J 2016;98-B(1 Suppl A):23–6

Aims. The primary aim of this study was to assess the independent association of the coronavirus disease 2019 (COVID-19) on postoperative mortality for patients undergoing orthopaedic and trauma surgery. The secondary aim was to identify factors that were associated with developing COVID-19 during the postoperative period. Methods. A multicentre retrospective study was conducted of all patients presenting to nine centres over a 50-day period during the COVID-19 pandemic (1 March 2020 to 19 April 2020) with a minimum of 50 days follow-up. Patient demographics, American Society of Anesthesiologists (ASA) grade, priority (urgent or elective), procedure type, COVID-19 status, and postoperative mortality were recorded. Results. During the study period, 1,659 procedures were performed in 1,569 patients. There were 68 (4.3%) patients who were diagnosed with COVID-19. There were 85 (5.4%) deaths postoperatively. Patients who had COVID-19 had a significantly lower survival rate when compared with those without a proven SARS-CoV-2 infection (67.6% vs 95.8%, p < 0.001). When adjusting for confounding variables (older age (p < 0.001), female sex (p = 0.004), hip fracture (p = 0.003), and increasing ASA grade (p < 0.001)) a diagnosis of COVID-19 was associated with an increased mortality risk (hazard ratio 1.89, 95% confidence interval (CI) 1.14 to 3.12; p = 0.014). A total of 62 patients developed COVID-19 postoperatively, of which two were in the elective and 60 were in the urgent group. Patients aged > 77 years (odds ratio (OR) 3.16; p = 0.001), with increasing ASA grade (OR 2.74; p < 0.001), sustaining a hip (OR 4.56; p = 0.008) or periprosthetic fracture (OR 14.70; p < 0.001) were more likely to develop COVID-19 postoperatively. Conclusion. Perioperative COVID-19 nearly doubled the background postoperative mortality risk following surgery. Patients at risk of developing COVID-19 postoperatively (patients > 77 years, increasing morbidity, sustaining a hip or periprosthetic fracture) may benefit from perioperative shielding. Cite this article: Bone Joint J 2020;102-B(12):1774–1781

Implant-associated infection is a major source of morbidity in orthopaedic surgery. There has been extensive research into the development of materials that prevent biofilm formation, and hence, reduce the risk of infection. Silver nanoparticle technology is receiving much interest in the field of orthopaedics for its antimicrobial properties, and the results of studies to date are encouraging. Antimicrobial effects have been seen when silver nanoparticles are used in trauma implants, tumour prostheses, bone cement, and also when combined with hydroxyapatite coatings. Although there are promising results with in vitro and in vivo studies, the number of clinical studies remains small. Future studies will be required to explore further the possible side effects associated with silver nanoparticles, to ensure their use in an effective and biocompatible manner. Here we present a review of the current literature relating to the production of nanosilver for medical use, and its orthopaedic applications. Cite this article: Bone Joint J 2015; 97-B:582–9

The number of arthroplasties being undertaken is expected to grow year on year, and periprosthetic joint infections will be an increasing socioeconomic burden. The challenge to prevent and eradicate these infections has resulted in the emergence of several new strategies, which are discussed in this review. Cite this article: Bone Joint J 2015;97-B:1162–9

The Department of Health and the Public Health Laboratory Service established the Nosocomial Infection National Surveillance Scheme in order to standardise the collection of information about infections acquired in hospital in the United Kingdom and provide national data with which hospitals could measure their own performance. The definition of superficial incisional infection (skin and subcutaneous tissue), set by the Center for Disease Control (CDC), should meet at least one of the defined criteria which would confirm the diagnosis and determine the need for specific treatment. We have assessed the interobserver reliability of the criteria for superficial incisional infection set by the CDC in our current practice. The incisional site of 50 patients who had an elective primary arthroplasty of the hip or knee was evaluated independently by two orthopaedic clinical research fellows and two orthopaedic ward sisters for the presence or absence of surgical-site infection. Interobserver reliability was assessed by comparison of the criteria for wound infection used by the four observers using kappa reliability coefficients. Our study demonstrated that some of the components of the current CDC criteria were unreliable and we recommend their revision

Periprosthetic joint infection (PJI) complicates between 0.5% and 1.2% primary total hip arthroplasties (THAs) and may have devastating consequences. The traditional assessment of patients suffering from PJI has involved the serological study of inflammatory markers and microbiological analysis of samples obtained from the joint space. Treatment has involved debridement and revision arthroplasty performed in either one or two stages. . We present an update on the burden of PJI, strategies for its diagnosis and treatment, the challenge of resistant organisms and the need for definitive evidence to guide the treatment of PJI after THA. Cite this article: Bone Joint J 2016;98-B(1 Suppl A):27–30

The Control of Infection Committee at a specialist orthopaedic hospital prospectively collected data on all episodes of bacteriologically-proven deep infection arising after primary hip and knee replacements over a 15-year period from 1987 to 2001. There were 10 735 patients who underwent primary hip or knee replacement. In 34 of 5947 hip replacements (0.57%) and 41 of 4788 knee replacements (0.86%) a deep infection developed. The most common infecting micro-organism was coagulase-negative staphylococcus, followed by Staphylococcus aureus, enterococci and streptococci. Of the infecting organisms, 72% were sensitive to routine prophylactic antimicrobial agents. Of the infections, 29% (22) arose in the first three months following surgery, 35% between three months and one year (26), and 36% (27) after one year. Most cases were detected early and treated aggressively, with eradication of the infection in 96% (72). There was no significant change in the infection rate or type of infecting micro-organism over the course of this study. These results set a benchmark, and importantly emphasise that only 64% of peri-prosthetic infections arise within one year of surgery. These results also illustrate the advantages of conducting joint replacement surgery in the isolation of a specialist hospital

We examined the usefulness of neutrophil CD64 expression in detecting local musculoskeletal infection and the impact of antibiotics on its expression. Of 141 patients suspected of musculoskeletal infection, 46 were confirmed by microbiological culture to be infected and 95 had infection excluded. The median CD64 count of patients with localised infection was 2230 molecules per cell (interquartile range (IQR) 918 to 4592) and that of the patients without infection was 937 molecules per cell (IQR 648 to 1309) (p < 0.001). The level of CD64 correlated with the CRP level in patients with infection, but not in those without infection (r = 0.59, p < 0.01). Receiver operator characteristic curve analysis revealed that CD64 was a good predictor of local infection. When the patients were subdivided into two groups based on the administration of antibiotics at the time of CD64 sampling, the sensitivity for detecting infection was better in those who had not received antibiotics. These results suggest that measurement of CD64 expression is a useful marker for local musculoskeletal infection

We have studied prospectively the outcome of wound discharge in patients after arthroplasty of the hip and knee. Over a period of 3.5 years 530 primary arthroplasties were carried out in one hospital. Postoperative wound infections developed in 82. At a mean follow-up of two years a comparison was made between these patients and 82 with healthy wounds, in terms of symptoms and signs of deep infection. There was an incidence of 1.1% of early deep infection, within six weeks in all cases. The rate of ‘superficial’ infection was 17.3% in the hips, 10.5% in the knees and 14.3% in total. At a mean follow-up of 26 months, there were no significant differences between the patients with infected wounds and a matched group of patients with healthy wounds in terms of the ESR, level of C-reactive protein, white cell count and radiological scores, but clinical scores were significantly worse in the patients with infected knees (p < 0.05). The length of stay was also significantly longer in this group (mean 14.6 days in the healthy wound group, 19 days in the problem group; p < 0.005). There was, however, no convincing evidence that these wound infections led to deep infection and early revision in the early to medium follow-up period. A larger and longer prospective trial would be necessary to shed more light on this potential problem

Peri-prosthetic infection remains a leading cause of revision surgery. Recent publications from the American Musculoskeletal Infection Society have sought to establish a definition of peri-prosthetic infection based on clinical findings and laboratory investigations. The limitations of their approach are discussed and an alternative definition is proposed, which it is felt may better reflect the uncertainties encountered in clinical practice

As of April 2010 all NHS institutions in the United Kingdom are required to publish data on surgical site infection, but the method for collecting this has not been decided. We examined 7448 trauma and orthopaedic surgical wounds made in patients staying for at least two nights between 2000 and 2008 at our institution and calculated the rate of surgical site infection using three definitions: the US Centers for Disease Control, the United Kingdom Nosocomial Infection National Surveillance Scheme and the ASEPSIS system. On the same series of wounds, the infection rate with outpatient follow-up according to Centre for Disease Control was 15.45%, according to the UK Nosocomial infection surveillance was 11.32%, and according to ASEPSIS was 8.79%. These figures highlight the necessity for all institutions to use the same method for diagnosing surgical site infection. If different methods are used, direct comparisons will be invalid and published rates of infection will be misleading

The objective of this study was to determine the effectiveness of screening and successful treatment of methicillin-resistant Staphylococcus aureus (MRSA) colonisation in elective orthopaedic patients on the subsequent risk of developing a surgical site infection (SSI) with MRSA. We screened 5933 elective orthopaedic in-patients for MRSA at pre-operative assessment. Of these, 108 (1.8%) were colonised with MRSA and 90 subsequently underwent surgery. Despite effective eradication therapy, six of these (6.7%) had an SSI within one year of surgery. Among these infections, deep sepsis occurred in four cases (4.4%) and superficial infection in two (2.2%). The responsible organism in four of the six cases was MRSA. Further analysis showed that patients undergoing surgery for joint replacement of the lower limb were at significantly increased risk of an SSI if previously colonised with MRSA. We conclude that previously MRSA-colonised patients undergoing elective surgery are at an increased risk of an SSI compared with other elective patients, and that this risk is significant for those undergoing joint replacement of the lower limb. Furthermore, when an infection occurs, it is likely to be due to MRSA

Post-discharge surveillance of surgical site infection is necessary if accurate rates of infection following surgery are to be available. We undertook a prospective study of 376 knee and hip replacements in 366 patients in order to estimate the rate of orthopaedic surgical site infection in the community. The inpatient infection was 3.1% and the post-discharge infection rate was 2.1%. We concluded that the use of telephone interviews of patients to identify the group at highest risk of having a surgical site infection (those who think they have an infection) with rapid follow-up by a professional trained to diagnose infection according to agreed criteria is an effective method of identifying infection after discharge from hospital

The purpose of this article is to provide the reader with a seven-step checklist that could help in minimising the risk of PJI. The check list includes strategies that can be implemented pre-operatively such as medical optimisation, and reduction of the bioburden by effective skin preparation or actions taking during surgery such as administration of timely and appropriate antibiotics or blood conservation, and finally implementation of post-operative protocols such as efforts to minimise wound drainage and haematoma formation.

Cite this article: Bone Joint J 2016;98-B(1 Suppl A):18–22.

Bactericidal levels of antibiotics are difficult to achieve in infected total joint arthroplasty when intravenous antibiotics or antibiotic-loaded cement spacers are used, but intra-articular (IA) delivery of antibiotics has been effective in several studies. This paper describes a protocol for IA delivery of antibiotics in infected knee arthroplasty, and summarises the results of a pharmacokinetic study and two clinical follow-up studies of especially difficult groups: methicillin-resistant Staphylococcus aureus and failed two-stage revision. In the pharmacokinetic study, the mean synovial vancomycin peak level was 9242 (3956 to 32 150; sd 7608 μg/mL) among the 11 patients studied. Serum trough level ranged from 4.2 to 25.2 μg/mL (mean, 12.3 μg/mL; average of 9.6% of the joint trough value), which exceeded minimal inhibitory concentration. The success rate exceeded 95% in the two clinical groups. IA delivery of antibiotics is shown to be safe and effective, and is now the first option for treatment of infected total joint arthroplasty in our institution.

Cite this article: Bone Joint J 2016;98-B(1 Suppl A):31–6.