Aims. Fungal and mycobacterial periprosthetic joint infections (PJI) are rare events. Clinicians are wary of missing these diagnoses, often leading to the routine ordering of fungal and mycobacterial cultures on periprosthetic specimens. Our goal was to examine the utility of these cultures and explore a modern bacterial culture technique using bacterial blood culture bottles (BCBs) as an alternative. Methods. We performed a retrospective review of patients diagnosed with hip or knee PJI between 1 January 2010 and 31 December 2019, at the Mayo Clinic in Rochester, Minnesota, USA. We included patients aged 18 years or older who had fungal, mycobacterial, or both cultures performed together with bacterial cultures. Cases with positive fungal or mycobacterial cultures were reviewed using the electronic medical record to classify the microbiological findings as representing true infection or not. Results. There were 2,067 episodes of PJI diagnosed within the study period. A total of 3,629 fungal cultures and 2,923 mycobacterial cultures were performed, with at least one of these performed in 56% of episodes (n = 1,157). Test positivity rates of fungal and mycobacterial cultures were 5% (n = 179) and 1.2% (n = 34), respectively. After a comprehensive review, there were 40 true fungal and eight true mycobacterial PJIs. BCB were 90% sensitive in diagnosing true fungal PJI and 100% sensitive in detecting rapidly growing mycobacteria (RGM). Fungal stains were performed in 27 true fungal PJI but were only positive in four episodes (14.8% sensitivity). None of the mycobacterial stains was positive. Conclusion. Routine fungal and mycobacterial stains and cultures should not be performed as they have little clinical utility in the diagnosis of PJI and are associated with significant costs. Candida species and RGM are readily recovered using BCB. More research is needed to predict rare non-Candida fungal and slowly growing mycobacterial PJI that warrant specialized cultures. Cite this article: Bone Joint J 2022;104-B(1):53–58

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

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

Aims. During revision procedures for aseptic reasons, there remains a suspicion that failure may have been the result of an undetected subclinical infection. However, there is little evidence available in the literature about unexpected positive results in presumed aseptic revision spine surgery. The aims of our study were to estimate the prevalence of unexpected positive culture using sonication and to evaluate clinical characteristics of these patients. Patients and Methods. All patients who underwent a revision surgery after instrumented spinal surgery at our institution between July 2014 and August 2016 with spinal implants submitted for sonication were retrospectively analyzed. Only revisions presumed as aseptic are included in the study. During the study period, 204 spinal revisions were performed for diagnoses other than infection. In 38 cases, sonication cultures were not obtained, leaving a study cohort of 166 cases. The mean age of the cohort was 61.5 years (. sd. 20.4) and there were 104 female patients. Results. Sonication cultures were positive in 75 cases (45.2%). Hardware failure was the most common indication for revision surgery and revealed a positive sonication culture in 26/75 cases (35%) followed by adjacent segment disease (ASD) in 23/75 cases (30%). Cutibacterium acnes and Staphylococcus epidermidis were the most commonly isolated microorganisms, observed in 45% and 31% of cases, respectively. C. acnes was isolated in 65.2% of cases when the indication for revision surgery was ASD. Conclusion. Infection must always be considered as a possibility in the setting of spinal revision surgery, especially in the case of hardware failure, regardless of the lack of clinical signs. Sonication should be routinely used to isolate microorganisms adherent to implants. Cite this article: Bone Joint J 2019;101-B:621–624

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

Allografts of bone from the femoral head are often used in orthopaedic procedures. Although the donated heads are thoroughly tested microscopically before release by the bone bank, some surgeons take additional cultures in the operating theatre before implantation. There is no consensus about the need to take these cultures. We retrospectively assessed the clinical significance of the implantation of positive-cultured bone allografts. The contamination rate at retrieval of the allografts was 6.4% in our bone bank. Intra-operative cultures were taken from 426 femoral head allografts before implantation; 48 (11.3%) had a positive culture. The most frequently encountered micro-organism was coagulase-negative staphylococcus. Deep infection occurred in two of the 48 patients (4.2%). In only one was it likely that the same micro-organism caused the contamination and the subsequent infection. In our study, the rate of infection in patients receiving positive-cultured allografts at implantation was not higher than the overall rate of infection in allograft surgery suggesting that the positive cultures at implantation probably represent contamination and that the taking of additional cultures is not useful

We compared the use of broth culture medium for samples taken in theatre with the standard practice of placing tissue samples in universal containers. A total of 67 consecutive patients had standard multiple samples of deep tissue harvested at surgery and distributed equally in theatre either to standard universal containers or to broth culture medium. These samples were cultured by direct and enrichment methods. The addition of broth in theatre to standard practice led to an increase in sensitivity from 83% to 95% and an increase in negative predictive value from 77% to 91%. Placing tissue samples directly into broth in the operating theatre is a simple, inexpensive way to increase the sensitivity of cultures from infected patients, and does not appear to compromise the specificity of these cultures. Cite this article: Bone Joint J 2014;96-B:1566–70

We determined the rate of contamination of donated femoral heads at primary hip arthroplasty within a single region between July 1992 and July 2001. We established the null hypothesis that culture results played no role in predicting early failure of the joint because of infection. The rate of contamination was 9%. A positive culture, at the time of retrieval, was found in 367 of 4045 femoral heads. Coagulase-negative staphylococcus was isolated in 77% of the positive cases. At a minimum follow-up of one year, there was no statistically significant difference in the rate of complications or of revision of age-matched patients whose femoral heads had a positive culture compared with those whose femoral heads were sterile. Our findings confirm that culture of the femoral head plays no part in determining future failure of joint replacement in the donor

Bovine and human articular chondrocytes were seeded in 2% alginate constructs and cultured for up to 19 days in a rotating-wall-vessel (RWV) and under static conditions. Culture within the RWV enhanced DNA levels for bovine chondrocyte-seeded constructs when compared with static conditions but did not produce enhancement for human cells. There was a significant enhancement of glycosaminoglycans and hydroxyproline synthesis for both bovine and human chondrocytes. In all cases, histological analysis revealed enhanced Safranin-O staining in the peripheral regions of the constructs compared with the central region. There was an overall increase in staining intensity after culture within the RWV compared with static conditions. Type-II collagen was produced by both bovine and human chondrocytes in the peripheral and central regions of the constructs and the staining intensity was enhanced by culture within the RWV. A capsule of flattened cells containing type-I collagen developed around the constructs maintained under static conditions when seeded with either bovine or human chondrocytes, but not when cultured within the RWV bioreactor

Fresh-frozen allograft bone is frequently used in orthopaedic surgery. We investigated the incidence of allograft-related infection and analysed the outcomes of recipients of bacterial culture-positive allografts from our single-institute bone bank during bone transplantation. The fresh-frozen allografts were harvested in a strict sterile environment during total joint arthroplasty surgery and immediately stored in a freezer at -78º to -68º C after packing. Between January 2007 and December 2012, 2024 patients received 2083 allografts with a minimum of 12 months of follow-up. The overall allograft-associated infection rate was 1.2% (24/2024). Swab cultures of 2083 allografts taken before implantation revealed 21 (1.0%) positive findings. The 21 recipients were given various antibiotics at the individual orthopaedic surgeon’s discretion. At the latest follow-up, none of these 21 recipients displayed clinical signs of infection following treatment. Based on these findings, we conclude that an incidental positive culture finding for allografts does not correlate with subsequent surgical site infection. Additional prolonged post-operative antibiotic therapy may not be necessary for recipients of fresh-frozen bone allograft with positive culture findings. Cite this article: Bone Joint J 2015;97-B:427–31

We compared the changes in the ratio of type-I and type-II collagen in monolayer cultures of human articular chondrocytes (HAC). HAC were isolated from samples of cartilage from normal joints and cultivated in monolayer for up to 46 days. Expression of collagen type-I and type-II was determined by immunocytochemistry, Western blotting, and the nested reverse transcription polymerase chain reaction (RT-PCR), and quantified by real-time PCR. The transition from a spherical morphology to the flattened morphology of an anchorage-dependent culture was accompanied by a rapid change in the collagen phenotype with the replacement of collagen type II by collagen type I. This was confirmed by immunocytochemistry and Western blotting between days 21 and 28. Using techniques for the analysis of gene transcription (nested RT-PCR and real-time PCR), a complete switch of collagen gene expression was not observed. Expression of collagen type I increased 100-fold during the culture time. That of collagen type II was found during the entire period and decreased more than 100-fold. The main finding was that expression of the genes encoding collagen type I and II was highly time-dependent and the ratio of collagen type II to I (CII/CI), defined as an index of cell differentiation, was significantly higher (215- to 480-fold) at the beginning of the culture. At the end of the experimental culture time, ratios between 0.1 and 1 were reached

Colchicine is often used in the treatment of diseases such as familial Mediterranean fever (FMF) and gout. We have previously reported that patients with FMF who had colchicine on a daily basis and who had a total hip arthroplasty showed no heterotopic ossification after surgery. The mechanism by which colchicine causes this clinical phenomenon has never been elucidated. We therefore evaluated the effect of various concentrations of colchicine on cell proliferation and mineralisation in tissue culture, using rat and human cells with and without osteogenic potential. Cell proliferation was assessed by direct cell counts and uptake of (. 3. H)thymidine, and mineralisation by measuring the amount of staining by Alizarin Red. Our findings indicate that concentrations of colchicine of up to 3 ng/ml did not affect cell proliferation but inhibition was observed at 10 to 30 ng/ml. Mineralisation decreased to almost 50%, which was the maximum inhibition observed, at concentrations of colchicine of 2.5 ng/ml. These results indicate that colchicine at low concentrations, of up to 3 ng/ml, has the capacity to inhibit selectively bone-like cell mineralisation in culture, without affecting cell proliferation. Further clinical and laboratory studies are necessary to evaluate the effects of colchicine on biological processes involving the proliferation of osteoblasts and tissue mineralisation in vivo, such as the healing of fractures, the formation of heterotopic bone and neoplastic bone growth

In 78 consecutive patients, we performed fine-needle aspiration of the hip before revision surgery. At the revision operation biopsies were taken from the capsule and joint tissues. The aspirate and the homogenised soft-tissue specimens were cultured using a radiometric technique. Fifteen hips proved to be infected and 63 sterile on culture of the tissues taken during revision surgery; 94% of the aspiration results were correct. The sensitivity of the technique was 87% and the specificity 95%. Fine-needle aspiration combined with a radiometric culture technique is a simple and reliable method of diagnosing infection of hip prostheses

Wear debris was extracted from 21 worn hip and knee replacements. Its mutagenic effects were tested on human cells in tissue culture using the micronucleus assay and fluorescent in situ hybridisation. The extracted wear debris increased the level of micronuclei in a linear dose-dependent manner but with a tenfold difference between samples. The concentration of titanium +/− vanadium and aluminium within the wear debris was linearly related both to the level of centromere-positive micronuclei in tissue culture, indicating an aneuploid event, and to the level of aneuploidy in vivo in peripheral blood lymphocytes. The concentration of cobalt and chromium +/− nickel and molybdenum in the wear debris correlated with the total index of micronuclei in tissue culture, both centromere-positive and centromere-negative i.e. both chromosomal breakage and aneuploidy events. The results show that wear debris can damage chromosomes in a dose-dependent manner which is specific to the type of metal. The results from studies in vitro correlate with those in vivo and suggest that the wear debris from a worn implant is at least partly responsible for the chromosomal damage which is seen in vivo

Peri-tendinous injection of local anaesthetic, both alone and in combination with corticosteroids, is commonly performed in the treatment of tendinopathies. Previous studies have shown that local anaesthetics and corticosteroids are chondrotoxic, but their effect on tenocytes remains unknown. We compared the effects of lidocaine and ropivacaine, alone or combined with dexamethasone, on the viability of cultured bovine tenocytes. Tenocytes were exposed to ten different conditions: 1) normal saline; 2) 1% lidocaine; 3) 2% lidocaine; 4) 0.2% ropivacaine; 5) 0.5% ropivacaine; 6) dexamethasone (dex); 7) 1% lidocaine+dex; 8) 2% lidocaine+dex; 9) 0.2% ropivacaine+dex; and 10) 0.5% ropivacaine+dex, for 30 minutes. After a 24-hour recovery period, the viability of the tenocytes was quantified using the CellTiter-Glo viability assay and fluorescence-activated cell sorting (FACS) for live/dead cell counts. A 30-minute exposure to lidocaine alone was significantly toxic to the tenocytes in a dose-dependent manner, but a 30-minute exposure to ropivacaine or dexamethasone alone was not significantly toxic.

Dexamethasone potentiated ropivacaine tenocyte toxicity at higher doses of ropivacaine, but did not potentiate lidocaine tenocyte toxicity. As seen in other cell types, lidocaine has a dose-dependent toxicity to tenocytes but ropivacaine is not significantly toxic. Although dexamethasone alone is not toxic, its combination with 0.5% ropivacaine significantly increased its toxicity to tenocytes. These findings might be relevant to clinical practice and warrant further investigation.

We cultured human osteoblasts from trabecular bone explants and confirmed their phenotype by alkaline phosphatase assay, increased cyclic adenosine monophosphate production in response to prostaglandin E2 and radiographic micro-analysis of nodules of calcification. The osteoblasts were seeded on to demineralised human bone fragments and examined at ten-day intervals over a 50-day period by scanning electron microscopy. During this time the bank bone became progressively repopulated by the cultured osteoblasts. This system may offer a means of graft enhancement in elective orthopaedic and maxillofacial surgery by delivery of cultured autologous human osteoblasts to bone defects.

Aims. Cutibacterium acnes (C. acnes; previously known as Propionibacterium acnes or P. acnes) periprosthetic hip and knee infections are under-reported. While culture contamination with C. acnes occurs, true infections are important to recognize and treat. We sought to describe the demographics and treatment outcomes of patients with C. acnes periprosthetic joint infections (PJIs) of the hip and knee. Methods. Patients with C. acnes PJI between January 2005 and December 2018 were retrospectively reviewed utilizing the institutional total joint registry. Patients with monomicrobial PJI and two or more positive cultures were considered to have true C. acnes PJI. Patients with polymicrobial infection or with only one positive culture were excluded. This resulted in 35 PJIs (21 hips and 14 knees); the patients’ mean age was 63 years (35 to 84) and 15 (43%) were female. Mean follow-up was five years (1 to 14). Results. The median time to positive culture was five days (IQR 5 to 6) and median synovial fluid cell count was 22,583 cells (IQR 15,200 to 53,231). The median ESR was 25 mm/hr (IQR 7 to 37), and CRP was 15 mg/l (IQR 3 to 29). Of the 35 PJIs, 18 (51%) were treated with chronic antibiotic suppression without surgical intervention, and the remainder were treated with two-stage exchange arthroplasty. The two-year survival free of any revision was 94%. Four patients failed treatment due to symptomatic infection, with three treated with two-stage exchange and one treated with irrigation and debridement with modular component exchange for a survival rate of 89% and 83% at two and five years, respectively. Conclusion. Laboratory evidence of C. acnes PJI in this cohort was typical compared to more conventional organisms. Cultures grew more quickly than previously thought in patients with C. acnes PJI. Treatment with two-stage exchange or chronic antibiotic suppression alone both had few treatment failures at mid-term follow-up. Cite this article: Bone Joint J 2024;106-B(12):1426–1430

Aims. Accurate diagnosis of chronic periprosthetic joint infection (PJI) presents a significant challenge for hip surgeons. Preoperative diagnosis is not always easy to establish, making the intraoperative decision-making process crucial in deciding between one- and two-stage revision total hip arthroplasty (THA). Calprotectin is a promising point-of-care novel biomarker that has displayed high accuracy in detecting PJI. We aimed to evaluate the utility of intraoperative calprotectin lateral flow immunoassay (LFI) in THA patients with suspected chronic PJI. Methods. The study included 48 THAs in 48 patients with a clinical suspicion of PJI, but who did not meet European Bone and Joint Infection Society (EBJIS) PJI criteria preoperatively, out of 105 patients undergoing revision THA at our institution for possible PJI between November 2020 and December 2022. Intraoperatively, synovial fluid calprotectin was measured with LFI. Cases with calprotectin levels ≥ 50 mg/l were considered infected and treated with two-stage revision THA; in negative cases, one-stage revision was performed. At least five tissue cultures were obtained; the implants removed were sent for sonication. Results. Calprotectin was positive (≥ 50 mg/l) in 27 cases; out of these, 25 had positive tissue cultures and/or sonication. Calprotectin was negative in 21 cases. There was one false negative case, which had positive tissue cultures. Calprotectin showed an area under the curve of 0.917, sensitivity of 96.2%, specificity of 90.9%, positive predictive value of 92.6%, negative predictive value of 95.2%, positive likelihood ratio of 10.6, and negative likelihood ratio of 0.04. Overall, 45/48 patients were correctly diagnosed and treated by our algorithm, which included intraoperative calprotectin measurement. This yielded a 93.8% concordance with postoperatively assessed EBJIS criteria. Conclusion. Calprotectin can be a valuable tool in facilitating the intraoperative decision-making process for cases in which chronic PJI is suspected and diagnosis cannot be established preoperatively. Cite this article: Bone Joint J 2024;106-B(5 Supple B):118–124

Aims. This study aimed to investigate the clinical characteristics and outcomes associated with culture-negative limb osteomyelitis patients. Methods. A total of 1,047 limb osteomyelitis patients aged 18 years or older who underwent debridement and intraoperative culture at our clinic centre from 1 January 2011 to 31 December 2020 were included. Patient characteristics, infection eradication, and complications were analyzed between culture-negative and culture-positive cohorts. Results. Of these patients, 264 (25.2%) had negative cultures. Patients with a culture-negative compared with a culture-positive status were more likely to have the following characteristics: younger age (≤ 40 years) (113/264 (42.8%) vs 257/783 (32.8%); p = 0.004), a haematogenous aetiology (75/264 (28.4%) vs 150/783 (19.2%); p = 0.002), Cierny-Mader host A (79/264 (29.9%) vs 142/783 (18.1%); p < 0.001), antibiotic use before sampling (34/264 (12.9%) vs 41/783 (5.2%); p＜0.001), fewer taken samples (n＜3) (48/264 (18.2%) vs 60/783 (7.7%); p＜0.001), and less frequent presentation with a sinus (156/264 (59.1%) vs 665/783 (84.9%); p < 0.001). After initial treatments of first-debridement and antimicrobial, infection eradication was inferior in culture-positive osteomyelitis patients, with a 2.24-fold increase (odds ratio 2.24 (95% confidence interval 1.42 to 3.52)) in the redebridement rate following multivariate analysis. No statistically significant differences were found in long-term recurrence and complications within the two-year follow-up. Conclusion. We identified several factors being associated with the culture-negative result in osteomyelitis patients. In addition, the data also indicate that culture negativity is a positive prognostic factor in early infection eradication. These results constitute the basis of optimizing clinical management and patient consultations. Cite this article: Bone Joint J 2024;106-B(7):720–727

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. The purpose of this study was to evaluate unexpected positive cultures in total hip arthroplasty (THA) revisions for presumed aseptic loosening, to assess the prevalence of low-grade infection using two definition criteria, and to analyze its impact on implant survival after revision. Methods. A total of 274 THA revisions performed for presumed aseptic loosening from 2012 to 2016 were reviewed. In addition to obtaining intraoperative tissue cultures from all patients, synovial and sonication fluid samples of the removed implant were obtained in 215 cases (79%) and 101 cases (37%), respectively. Histopathological analysis was performed in 250 cases (91%). Patients were classified as having low-grade infections according to institutional criteria and Musculoskeletal Infection Society (MSIS) International Consensus Meeting (ICM) 2013 criteria. Low-grade infections according to institutional criteria were treated with targeted antibiotics for six weeks postoperatively. Implant failure was defined as the need for re-revision resulting from periprosthetic joint infection (PJI) and aseptic reasons. The mean follow-up was 68 months (26 to 95). Results. Unexpected positive intraoperative samples were found in 77 revisions (28%). Low-grade infection was diagnosed in 36 cases (13%) using institutional criteria and in nine cases (3%) using MSIS ICM 2013 criteria. In all, 41 patients (15%) had single specimen growth of a low-virulent pathogen and were deemed contaminated. Coagulase-negative Staphylococcus and anaerobes were the most commonly isolated bacteria. Implant failure for PJI was higher in revisions with presumed contaminants (5/41, 12%) compared to those with low-grade infections (2/36, 6%) and those with negative samples (5/197, 3%) (p = 0.021). The rate of all-cause re-revision was similar in patients diagnosed with low-grade infections (5/36, 14%) and those with presumed contaminants (6/41, 15%) and negative samples (21/197, 11%) (p = 0.699). Conclusion. Our findings suggest that the presumption of culture contamination in aseptic revision hip arthroplasty may increase the detection of PJI. In this cohort, the presence of low-grade infection did not increase the risk of re-revision. Further studies are needed to assess the relevance of single specimen growth and the benefits of specific postoperative antibiotic regimens. Cite this article: Bone Joint J 2021;103-B(6):1070–1077

Aims. In cases of severe periprosthetic joint infection (PJI) of the knee, salvage procedures such as knee arthrodesis (KA) or above-knee amputation (AKA) must be considered. As both treatments result in limitations in quality of life (QoL), we aimed to compare outcomes and factors influencing complication rates, mortality, and mobility. Methods. Patients with PJI of the knee and subsequent KA or AKA between June 2011 and May 2021 were included. Demographic data, comorbidities, and patient history were analyzed. Functional outcomes and QoL were prospectively assessed in both groups with additional treatment-specific scores after AKA. Outcomes, complications, and mortality were evaluated. Results. A total of 98 patients were included, 52 treated with arthrodesis and 47 with AKA. The mean number of revision surgeries between primary arthroplasty and arthrodesis or AKA was 7.85 (SD 5.39). Mean follow-up was 77.7 months (SD 30.9), with a minimum follow-up of two years. Complications requiring further revision surgery occurred in 11.5% of patients after arthrodesis and in 37.0% of AKA patients. Positive intraoperative tissue cultures obtained during AKA was significantly associated with the risk of further surgical revision. Two-year mortality rate of arthrodesis was significantly lower compared to AKA (3.8% vs 28.3%), with age as an independent risk factor in the AKA group. Functional outcomes and QoL were better after arthrodesis compared to AKA. Neuropathic pain was reported by 19 patients after AKA, and only 45.7% of patients were fitted or were intended to be fitted with a prosthesis. One-year infection-free survival after arthrodesis was 88.5%, compared to 78.5% after AKA. Conclusion. Above-knee amputation in PJI results in high complication and mortality rates and poorer functional outcome compared to arthrodesis. Mortality rates after AKA depend on patient age and mobility, with most patients not able to be fitted with a prosthesis. Therefore, arthrodesis should be preferred whenever possible if salvage procedures are indicated. Cite this article: Bone Joint J 2024;106-B(7):669–679

Aims. Removal of infected components and culture-directed antibiotics are important for the successful treatment of chronic periprosthetic joint infection (PJI). However, as many as 27% of chronic PJI patients yield negative culture results. Although culture negativity has been thought of as a contraindication to one-stage revision, data supporting this assertion are limited. The aim of our study was to report on the clinical outcomes for one-stage and two-stage exchange arthroplasty performed in patients with chronic culture-negative PJI. Methods. A total of 105 consecutive patients who underwent revision arthroplasty for chronic culture-negative PJI were retrospectively evaluated. One-stage revision arthroplasty was performed in 30 patients, while 75 patients underwent two-stage exchange, with a minimum of one year's follow-up. Reinfection, re-revision for septic and aseptic reasons, amputation, readmission, mortality, and length of stay were compared between the two treatment strategies. Results. The patient demographic characteristics did not differ significantly between the groups. At a mean follow-up of 4.2 years, the treatment failure for reinfection for one-stage and two-stage revision was five (16.7%) and 15 patients (20.0%) (p = 0.691), and for septic re-revision was four (13.3%) and 11 patients (14.7%) (p = 0.863), respectively. No significant differences were observed between one-stage and two-stage revision for 30- 60- and 90-day readmissions (10.0% vs 8.0%; p = 0.714; 16.7% vs 9.3%; p = 0.325; and 26.7% vs 10.7%; p = 0.074), one-year mortality (3.3% vs 4.0%; p > 0.999), and amputation (3.3% vs 1.3%; p = 0.496). Conclusion. In this non-randomized study, one-stage revision arthroplasty demonstrated similar outcomes including reinfection, re-revision, and readmission rates for the treatment of chronic culture-negative PJI after TKA and THA compared to two-stage revision. This suggests culture negativity may not be a contraindication to one-stage revision arthroplasty for chronic culture-negative PJI in selected patients. Cite this article: Bone Joint J 2021;103-B(3):515–521

Aims. As an increasing number of female surgeons are choosing orthopaedics, it is important to recognize the impact of pregnancy within this cohort. The aim of this review was to examine common themes and data surrounding pregnancy, parenthood, and fertility within orthopaedics. Methods. A systematic review was conducted by searching Medline, Emcare, Embase, PsycINFO, OrthoSearch, and the Cochrane Library in November 2022. The Preferred Reporting Items for Systematic Reviews and Meta Analysis were adhered to. Original research papers that focused on pregnancy and/or parenthood within orthopaedic surgery were included for review. Results. Of 1,205 papers, 19 met the inclusion criteria. Our results found that orthopaedic surgeons have higher reported rates of obstetric complications, congenital abnormalities, and infertility compared to the general population. They were noted to have children at a later age and voluntarily delayed childbearing. Negative perceptions of pregnancy from fellow trainees and programme directors were identified. Conclusion. Female orthopaedic surgeons have high rates of obstetric complications and infertility. Negative perceptions surrounding pregnancy can lead to orthopaedic surgeons voluntarily delaying childbearing. There is a need for a pregnancy-positive culture shift combined with formalized guidelines and female mentorship to create a more supportive environment for pregnancy within orthopaedic surgery. Cite this article: Bone Joint J 2023;105-B(8):857–863

Aims. Of growing concern in arthroplasty is the emergence of atypical infections, particularly Cutibacterium (formerly Propionibacterium) sp. infections. Currently, the dermal colonization rate of Cutibacterium about the hip is unknown. Therefore, the aim of this study was to investigate colonization rates of Cutibacterium sp. at locations approximating anterior and posterolateral approaches to the hip joint. Methods. For this non-randomized non-blinded study, 101 adult patients scheduled for hip or knee surgery were recruited. For each, four 3 mm dermal punch biopsies were collected after administration of anaesthesia, but prior to antibiotics. Prebiopsy skin preparation consisted of a standardized preoperative 2% chlorhexidine skin cleansing protocol and an additional 70% isopropyl alcohol mechanical skin scrub immediately prior to biopsy collection. Two skin samples 10 cm apart were collected from a location approximating a standard direct anterior skin incision, and two samples 10 cm apart were collected from a lateral skin incision (suitable for posterior, direct-lateral, or anterolateral approaches). Samples were cultured for two weeks using a protocol optimized for Cutibacterium. Results. A total of 23 out of 404 cultures (collected from 101 patients) were positive for a microorganism, with a total of 22 patients having a positive culture (22%). Overall, 15 of the cultures in 14 patients were positive for Cutibacterium sp. (65%), of which Cutibacterium acnes comprised the majority (n = 13; 87%). Other isolated microorganisms include coagulase-negative Staphylococcus (n = 6), Clostridium (n = 1), and Corynebacterium (n = 1). Of all positive cultures, 15 were obtained from the anterior location (65%), of which seven (60%) were from the most proximal biopsy location. However, these findings were not statistically significant (anterior vs lateral, p = 0.076; proximal vs distal, p =0.238). Conclusion. Approximately 14% (14/101) of the patients demonstrated a positive Cutibacterium colonization about the hip, the majority anteriorly. Given the high colonization rate of Cutibacterium, alternative skin preparations for total hip arthroplasty should be considered. Cite this article: Bone Joint J 2020;102-B(7 Supple B):52–56

Aims. As a proven and comprehensive molecular technique, metagenomic next-generation sequencing (mNGS) has shown its potential in the diagnosis of pathogens in patients with periprosthetic joint infection (PJI), using a single type of specimen. However, the optimal use of mNGS in the management of PJI has not been explored. In this study, we evaluated the diagnostic value of mNGS using three types of specimen with the aim of achieving a better choice of specimen for mNGS in these patients. Methods. In this prospective study, 177 specimens were collected from 59 revision arthroplasties, including periprosthetic tissues, synovial fluid, and prosthetic sonicate fluid. Each specimen was divided into two, one for mNGS and one for culture. The criteria of the Musculoskeletal Infection Society were used to define PJI (40 cases) and aseptic failure (19 cases). Results. The sensitivity and specificity of mNGS in the diagnosis of PJI were 95% and 94.7%, respectively, for all types of specimen. The sensitivity and specificity were 65% and 100%, respectively, for periprosthetic tissues, 87.5% and 94.7%, respectively, for synovial fluid, and 92.5% and 94.7%, respectively, for prosthetic sonicate fluid. The mNGS of prosthetic sonicate fluid outperformed that for other types of specimen in the rates of detection of pathogens (84.6%), sequencing reads (> ten-fold) and the rate of genome coverage (> five-fold). Conclusion. mNGS could serve as an accurate diagnostic tool in the detection of pathogens in patients with a PJI using three types of specimen. Due to its superior perfomance in identifying a pathogen, mNGS of prosthetic sonicate fluid provides the most value and may partly replace traditional tests such as bacteriological culture in these patients. Cite this article: Bone Joint J 2021;103-B(5):923–930

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

Aims. We aimed to report the mid- to long-term rates of septic and aseptic failure after two-stage revision surgery for periprosthetic joint infection (PJI) following total hip arthroplasty (THA). Methods. We retrospectively reviewed 96 cases which met the Musculoskeletal Infection Society criteria for PJI. The mean follow-up was 90 months (SD 32). Septic failure was assessed using a Delphi-based consensus definition. Any further surgery undertaken for aseptic mechanical causes was considered as aseptic failure. The cumulative incidence with competing risk analysis was used to predict the risk of septic failure. A regression model was used to evaluate factors associated with septic failure. The cumulative incidence of aseptic failure was also analyzed. Results. There were 23 septic failures at final follow-up, with a cumulative incidence of 14% (95% confidence interval (CI) 8% to 22%) at one year, 18% (95% CI 11% to 27%) at two years, 22% (95% CI 14% to 31%) at five years, and 23% (95% CI 15% to 33%) at ten years. Having at least one positive culture (hazard ratio (HR) 2.38 (interquartile range (IQR) 1.19 to 4.74); p = 0.013), or a positive intraoperative frozen section (HR 2.55 (IQR 1.06 to 6.15); p = 0.037) was significantly associated with septic failure after reimplantation. With dislocation being the most common cause of aseptic revision (5.2%), the cumulative incidence of aseptic failure was 1% (95% CI 0% to 5%) at one year, 6% (95% CI 1% to 8%) at five years, and 8% (95%CI 3% to 17%) at ten years. Conclusion. If there is no recurrent infection in the five years following reimplantation, the chances of further infection thereafter are remote. While the results of a frozen section may be a reliable guide to the timing of reimplantation, intraoperative culture has, currently, only prognostic value. Surgeons should be aware that instability remains a potential indication for further revision surgery. Cite this article: Bone Joint J 2021;103-B(1):79–86

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. Methods. A total of 284 patients with clinically and radiologically suspected infectious spondylodiscitis were prospectively recruited into the study. Image-guided biopsy of the vertebral lesion was performed and specimens were sent for various microbiological tests and histological examinations. The final diagnosis was determined using a composite reference standard based on clinical, radiological, serological, microbiological, and histological findings. The overall diagnostic yield of the biopsy, and that for each test, was calculated in light of the final diagnosis. Results. The final diagnosis was tuberculous spondylodiscitis in 250 patients (88%) and pyogenic spondylodiscitis in 22 (7.8%). Six (2.1%) had a noninfectious condition-mimicking infectious spondylodiscitis, and six (2.1%) had no definite diagnosis and improved without specific treatment. The diagnosis was made by image-guided biopsy in 152 patients (56%) with infectious spondylodiscitis. Biopsy was contributory in identifying 132/250 patients (53%) with tuberculous spondylodiscitis, and 20/22 patients (91%) with pyogenic spondylodiscitis. Histological examination was the most sensitive diagnostic modality, followed by Xpert MTB/RIF assay. Conclusion. Image-guided biopsy has a reasonably high diagnostic yield in patients with suspected infectious spondylodiscitis. A combination of histological examination, Xpert MTB/RIF assay, bacterial culture, and sensitivity provides high diagnostic accuracy in a country in which TB is endemic. Cite this article: Bone Joint J 2022;104-B(1):120–126

Aims. This study aimed to assess the performance of an automated multiplex polymerase chain reaction (mPCR) technique for rapid diagnosis of native joint septic arthritis. Patients and Methods. Consecutive patients with suspected septic arthritis undergoing aseptic diagnostic joint aspiration were included. The aspirate was used for analysis by mPCR and conventional microbiological analysis. A joint was classed as septic according to modified Newman criteria. Based on receiver operating characteristic (ROC) analysis, the area under the ROC curve (AUC) values of the mPCR and the synovial fluid culture were compared using the z-test. A total of 72 out of 76 consecutive patients (33 women, 39 men; mean age 64 years (22 to 92)) with suspected septic arthritis were included in this study. Results. Of 72 patients, 42 (58%) were deemed to have septic joints. The sensitivity of mPCR and synovial fluid culture was 38% and 29%, respectively. No significant differences were found between the AUCs of both techniques (p = 0.138). A strong concordance of 89% (Cohen’s kappa: 0.65) was shown. The mPCR failed to detect Staphylococcus aureus (n = 1) and Streptococcus pneumoniae (n = 1; no primer included in the mPCR), whereas the synovial fluid culture missed six microorganisms (positive mPCR: S. aureus (n = 2), Cutibacterium acnes (n = 3), coagulase-negative staphylococci (n = 2)). Conclusion. The automated mPCR showed at least a similar performance to the synovial fluid culture (the current benchmark) in diagnosing septic arthritis, having the great advantage of a shorter turnaround time (within five hours). Cite this article: Bone Joint J 2019;101-B:288–296

Aims. Positive cultures are not uncommon in cases of revision total knee and hip arthroplasty (TKA and THA) for presumed aseptic causes. The purpose of this study was to assess the incidence of positive intra-operative cultures in presumed aseptic revision of TKA and THA, and to determine whether the presence of intra-operative positive cultures results in inferior survival in such cases. Patients and Methods. A retrospective cohort study was assembled with 679 patients undergoing revision knee (340 cases) or hip arthroplasty (339 cases) for presumed aseptic causes. For all patients three or more separate intra-operative cultures were obtained. Patients were diagnosed with a previously unsuspected prosthetic joint infection (PJI) if two or more cultures were positive with the same organism. Records were reviewed for demographic details, pre-operative laboratory results and culture results. The primary outcome measure was infection-free implant survival at two years. Results. The incidence of unsuspected PJI was 27 out of 340 (7.9%) in TKA and 41 out of 339 (12.1%) in THA. Following revision TKA, the rate of infection-free implant survival in patients with an unsuspected PJI was 88% (95% confidence intervals (CI) 60 to 97) at two years compared with 98% (95% CI 94 to 99) in patients without PJI (p = 0.001). After THA, the rate of survival was similar in those with unsuspected PJI (92% (95% CI 73 to 98) at two years) and those without (94% (95% CI 89 to 97), p = 0.31). Conclusion. Following revision of TKA and THA for aseptic diagnoses, around 10% of cases were found to have positive cultures. In the knee, such cases had inferior infection-free survival at two years compared with those with negative cultures; there was no difference between the groups following THA. Cite this article: Bone Joint J 2017;99-B:1482–9

Aims. In patients with a “dry” aspiration during the investigation of prosthetic joint infection (PJI), saline lavage is commonly used to obtain a sample for analysis. The aim of this study was to investigate prospectively the impact of saline lavage on synovial fluid analysis in revision arthroplasty. Methods. Patients undergoing revision hip (THA) or knee arthroplasty (TKA) for any septic or aseptic indication were enrolled. Intraoperatively, prior to arthrotomy, the maximum amount of fluid possible was aspirated to simulate a dry tap (pre-lavage) followed by the injection with 20 ml of normal saline and re-aspiration (post-lavage). Pre- and post-lavage synovial white blood cell (WBC) count, percent polymorphonuclear cells (%PMN), and cultures were compared. Results. A total of 78 patients had data available for analysis; 17 underwent revision THA and 61 underwent revision TKA. A total of 16 patients met modified Musculoskeletal Infection Society (MSIS) criteria for PJI. Pre- and post-lavage %PMNs were similar in septic patients (87% vs 85%) and aseptic patients (35% vs 39%). Pre- and post-lavage synovial fluid WBC count were far more disparate in septic (53,553 vs 8,275 WBCs) and aseptic (1,103 vs 268 WBCs) cohorts. At a cutoff of 80% PMN, the post-lavage aspirate had a sensitivity of 75% and specificity of 95%. At a cutoff of 3,000 WBCs, the post-lavage aspirate had a sensitivity of 63% and specificity of 98%. As the post-lavage synovial WBC count increased, the difference between pre- and post-lavage %PMN decreased (mean difference of 5% PMN in WBC < 3,000 vs mean difference 2% PMN in WBC > 3,000, p = 0.013). Of ten positive pre-lavage fluid cultures, only six remained positive post-lavage. Conclusion. While saline lavage aspiration significantly lowered the synovial WBC count, the %PMN remained similar, particularly at WBC counts of > 3,000. These findings suggest that in patients with a dry-tap, the %PMN of a saline lavage aspiration has reasonable sensitivity (75%) for the detection of PJI. Cite this article: Bone Joint J 2020;102-B(6 Supple A):138–144

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. The aim of this study was to establish the diagnostic accuracy of culture of joint aspirate with and without saline injection-reaspiration. Patients and Methods. This is a retrospective analysis of 580 hip and knee aspirations in patients who were deemed to have a moderate to high risk of infection, and who subsequently proceeded to revision arthroplasty over a period of 12 years. It was carried out at a large quaternary referral centre where preoperative aspiration is routine. Results. Fluid was aspirated primarily in 313 (54%) cases and after saline injection-reaspiration of a ‘dry tap’ in 267 (46%) cases. Overall sensitivity and specificity of the diagnostic aspirate were 84% (78% to 89%) and 85% (81% to 88%), respectively. Sensitivity and specificity of saline injection-reaspiration after ‘dry tap’ were 87% (79% to 92%) and 79% (72% to 84%) compared with 81% (71% to 88%) and 90% (85% to 93%) for direct aspiration. Conclusion. Preoperative joint aspiration and culture is a sensitive and specific test for the confirmation of diagnosis in patients at a moderate to high risk of prosthetic joint infection. Culture of saline injection-reaspiration also provides accurate diagnostic information in the event of a ‘dry tap’. Both methods allow susceptibility testing of relevant organisms and are therefore able to guide perioperative antibiotic therapy. Cite this article: Bone Joint J 2018;100-B:749–54

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

Aims. Prosthetic joint infection (PJI) and aseptic loosening in total hip arthroplasty (THA) can present with pain and osteolysis. The Musculoskeletal Infection Society (MSIS) has provided criteria for the diagnosis of PJI. The aim of our study was to analyze the utility of F18-fluorodeoxyglucose (FDG) positron emission tomography (PET) CT scan in the preoperative diagnosis of septic loosening in THA, based on the current MSIS definition of prosthetic joint infection. Patients and Methods. A total of 130 painful unilateral cemented THAs with a mean follow-up of 5.17 years (. sd. 1.12) were included in this prospective study. The mean patient age was 67.5 years (. sd. 4.85). Preoperative evaluation with inflammatory markers, aspiration, and an F18 FDG PET scan were performed. Diagnostic utility tests were also performed, based on the MSIS criteria for PJI and three samples positive on culture alone. Results. The mean erythrocyte sedimentation rate, C-reactive protein, and white cell count were 47.83 mm/hr, 25.21 mg/l, and 11.05 × 10. 9. /l, respectively. The sensitivity, specificity, accuracy, negative predictive value, and false-positive rate of FDG PET compared with MSIS criteria were 94.87%, 38.46 %, 56.38%, 94.59 %, and 60.21%, respectively. The false-positive rate of FDG PET compared with culture alone was 77.4%. Conclusion. FDG PET has a definitive role in the preoperative evaluation of suspected PJI. This the first study to evaluate its utility based on MSIS criteria and compare it with microbiology results alone. However, FDG PET has a high false-positive rate. Therefore, we suggest that F18 FDG PET is useful in confirming the absence of infection, but if positive, may not be confirmatory of PJI. Cite this article: Bone Joint J 2019;101-B:910–914

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

Aims. The aim of this study was to develop a single-layer hybrid organic-inorganic sol-gel coating that is capable of a controlled antibiotic release for cementless hydroxyapatite (HA)-coated titanium orthopaedic prostheses. Methods. Coatings containing gentamicin at a concentration of 1.25% weight/volume (wt/vol), similar to that found in commercially available antibiotic-loaded bone cement, were prepared and tested in the laboratory for: kinetics of antibiotic release; activity against planktonic and biofilm bacterial cultures; biocompatibility with cultured mammalian cells; and physical bonding to the material (n = 3 in all tests). The sol-gel coatings and controls were then tested in vivo in a small animal healing model (four materials tested; n = 6 per material), and applied to the surface of commercially pure HA-coated titanium rods. Results. The coating released gentamicin at > 10 × minimum inhibitory concentration (MIC) for sensitive staphylococcal strains within one hour thereby potentially giving effective prophylaxis for arthroplasty surgery, and showed > 99% elution of the antibiotic within the coating after 48 hours. There was total eradication of both planktonic bacteria and established bacterial biofilms of a panel of clinically relevant staphylococci. Mesenchymal stem cells adhered to the coated surfaces and differentiated towards osteoblasts, depositing calcium and expressing the bone marker protein, osteopontin. In the in vivo small animal bone healing model, the antibiotic sol-gel coated titanium (Ti)/HA rod led to osseointegration equivalent to that of the conventional HA-coated surface. Conclusion. In this study we report a new sol-gel technology that can release gentamicin from a bioceramic-coated cementless arthroplasty material. In vitro, local gentamicin levels are in excess of what can be achieved by antibiotic-loaded bone cement. In vivo, bone healing in an animal model is not impaired. This, thus, represents a biomaterial modification that may have the potential to protect at-risk patients from implant-related deep infection. Cite this article: Bone Joint J 2021;103-B(3):522–529

The gelatin-based haemostyptic compound Spongostan was tested as a three-dimensional (3D) chondrocyte matrix in an in vitro model for autologous chondrocyte transplantation using cells harvested from bovine knees. In a control experiment of monolayer cultures, the proliferation or de-differentiation of bovine chondrocytes was either not or only marginally influenced by the presence of Spongostan (0.3 mg/ml). In monolayers and 3-D Minusheet culture chambers, the cartilage-specific differentiation markers aggrecan and type-II collagen were ubiquitously present in a cell-associated fashion and in the pericellular matrix. The Minusheet cultures usually showed a markedly higher mRNA expression than monolayer cultures irrespective of whether Spongostan had been present or not during culture. Although the de-differentiation marker type-I collagen was also present, the ratio of type-I to type-II collagen or aggrecan to type-I collagen remained higher in Minusheet 3-D cultures than in monolayer cultures irrespective of whether Spongostan had been included in or excluded from the monolayer cultures. The concentration of GAG in Minusheet cultures reached its maximum after 14 days with a mean of 0.83 ± 0.8 μg/10. 6. cells; mean ±, . sem. , but remained considerably lower than in monolayer cultures with/without Spongostan. Our results suggest that Spongostan is in principle suitable as a 3-D chondrocyte matrix, as demonstrated in Minusheet chambers, in particular for a culture period of 14 days. Clinically, differentiating effects on chondrocytes, simple handling and optimal formability may render Spongostan an attractive 3-D scaffold for autologous chondrocyte transplantation

Aims. The aim of this study was to determine if a three-month course of microorganism-directed oral antibiotics reduces the rate of failure due to further infection following two-stage revision for chronic prosthetic joint infection (PJI) of the hip and knee. Methods. A total of 185 patients undergoing a two-stage revision in seven different centres were prospectively enrolled. Of these patients, 93 were randomized to receive microorganism-directed oral antibiotics for three months following reimplantation; 88 were randomized to receive no antibiotics, and four were withdrawn before randomization. Of the 181 randomized patients, 28 were lost to follow-up, six died before two years follow-up, and five with culture negative infections were excluded. The remaining 142 patients were followed for a mean of 3.3 years (2.0 to 7.6) with failure due to a further infection as the primary endpoint. Patients who were treated with antibiotics were also assessed for their adherence to the medication regime and for side effects to antibiotics. Results. Nine of 72 patients (12.5%) who received antibiotics failed due to further infection compared with 20 of 70 patients (28.6%) who did not receive antibiotics (p = 0.012). Five patients (6.9%) in the treatment group experienced adverse effects related to the administered antibiotics severe enough to warrant discontinuation. Conclusion. This multicentre randomized controlled trial showed that a three-month course of microorganism-directed, oral antibiotics significantly reduced the rate of failure due to further infection following a two-stage revision of total hip or knee arthroplasty for chronic PJI. Cite this article: Bone Joint J 2020;102-B(6 Supple A):3–9

Aims. Our aim was to investigate the prevalence of Propionibacterium (P.) acnes in the subcutaneous fat and capsule of patients undergoing shoulder surgery for frozen shoulder or instability. Patients and Methods. A total of 46 patients undergoing either an arthroscopic capsular release or stabilisation had biopsies taken from the subcutaneous fat and capsule of the shoulder at the time of surgery. These samples were sent for culture in enrichment, and also for Nucleic Acid Amplification testing. The prevalence of P. acnes and other microbes was recorded. Fisher's exact test of binary variables was used to calculate the association with significance set at p < 0.05. Assessment of influence of independent variables including a pre-operative glenohumeral injection, fat colonisation and gender, was undertaken using binary linear regression. Results. A total of 25 patients (53%) had P. acnes in one or more tissue samples and 35 (74%) had other bacterial species. The same microbe was found in the subcutaneous fat and the capsule in 13 patients (28%). There was no statistically significant association between the surgical pathology and capsular colonisation with P. acnes (p = 0.18) or mixed identified bacterial species (p = 0.77). Male gender was significantly associated with an increased capsular colonisation of P. acnes (odds ratio (OR) 12.38, 95% confidence interval (CI) 1.43 to 106.77, p = 0.02). A pre-operative glenohumeral injection was significantly associated with capsular P. acnes colonisation (OR 5.63, 95% CI 1.07 to 29.61, p = 0.04. Positive fat colonisation with P. acnes was significantly associated with capsular P. acnes (OR 363, 95% CI 20.90 to 6304.19, p < 0.01). Regression models pseudo R. 2. found fat colonisation with P. acnes to explain 70% of the variance of the model. Patients who had a pre-operative glenohumeral injection who were found intra-operatively to have fat colonisation with P. acnes had a statistically significant association with colonisation of their capsule with P. acnes (OR 165, 95% CI 13.51 to 2015.24, p < 0.01). Conclusion. These results show a statistically significant association between subcutaneous skin P. acnes culture and P. acnes capsular culture, especially when the patient has undergone a previous injection. The results refute the hypothesis that P. acnes causes frozen shoulder. Cite this article: Bone Joint J 2017;99-B:1067–72

Aims. Failure of irrigation and debridement (I&D) for prosthetic joint infection (PJI) is influenced by numerous host, surgical, and pathogen-related factors. We aimed to develop and validate a practical, easy-to-use tool based on machine learning that may accurately predict outcome following I&D surgery taking into account the influence of numerous factors. Methods. This was an international, multicentre retrospective study of 1,174 revision total hip (THA) and knee arthroplasties (TKA) undergoing I&D for PJI between January 2005 and December 2017. PJI was defined using the Musculoskeletal Infection Society (MSIS) criteria. A total of 52 variables including demographics, comorbidities, and clinical and laboratory findings were evaluated using random forest machine learning analysis. The algorithm was then verified through cross-validation. Results. Of the 1,174 patients that were included in the study, 405 patients (34.5%) failed treatment. Using random forest analysis, an algorithm that provides the probability for failure for each specific patient was created. By order of importance, the ten most important variables associated with failure of I&D were serum CRP levels, positive blood cultures, indication for index arthroplasty other than osteoarthritis, not exchanging the modular components, use of immunosuppressive medication, late acute (haematogenous) infections, methicillin-resistant Staphylococcus aureus infection, overlying skin infection, polymicrobial infection, and older age. The algorithm had good discriminatory capability (area under the curve = 0.74). Cross-validation showed similar probabilities comparing predicted and observed failures indicating high accuracy of the model. Conclusion. This is the first study in the orthopaedic literature to use machine learning as a tool for predicting outcomes following I&D surgery. The developed algorithm provides the medical profession with a tool that can be employed in clinical decision-making and improve patient care. Future studies should aid in further validating this tool on additional cohorts. Cite this article: Bone Joint J 2020;102-B(7 Supple B):11–19

Aims. This multicentre, retrospective study aimed to improve our knowledge of primary pyogenic spinal infections in children by analyzing a large consecutive case series. Patients and Methods. The medical records of children with such an infection, treated at four tertiary institutions between 2004 and 2014, were analyzed retrospectively. Epidemiological, clinical, paraclinical, radiological, and microbiological data were evaluated. There were 103 children, of whom 79 (76.7%) were aged between six months and four years. Results. We confirmed a significant male predominance in the incidence of primary pyogenic spinal infections in children (65%). The lumbar spine was the most commonly affected region, and 27 infections (26.2%) occurred at L4/5. The white blood cell count was normal in 61 children (59%), and the CRP level was normal in 43 (42%). Blood cultures were performed in 95 children, and were positive in eight (8%). A total of 20 children underwent culture of biopsy or aspiration material, which was positive in eight (40%). Methicillin-sensitive Staphylococcus aureus (MSSA) and Kingella (K.) kingae were the most frequently isolated pathogens. Conclusion. MSSA remains the most frequently isolated pathogen in children with primary pyogenic infection of the spine, but K. kingae should be considered as an important pathogen in children aged between six months and four years. Therefore, an empirical protocol for antibiotic treatment should be used, with consideration being made for the triphasic age distribution and specific bacteriological aetiology. In the near future, the results of polymerase chain reaction assay on throat swabs may allow the indirect identification of K. kingae spondylodiscitis in young children and thus aid early treatment. However, these preliminary results require validation by other prospective multicentre studies. Cite this article: Bone Joint J 2018;100-B:542–8

Periprosthetic joint infection represents a devastating complication after total elbow arthroplasty. Several measures can be implemented before, during, and after surgery to decrease infection rates, which exceed 5%. Debridement with antibiotics and implant retention has been reported to be successful in less than one-third of acute infections, but still plays a role. For elbows with well-fixed implants, staged retention seems to be equally successful as the more commonly performed two-stage reimplantation, both with a success rate of 70% to 80%. Permanent resection or even amputation are occasionally considered. Not uncommonly, a second-stage reimplantation requires complex reconstruction of the skeleton with allografts, and the extensor mechanism may also be deficient. Further developments are needed to improve our management of infection after elbow arthroplasty.

Cite this article: Bone Joint J 2024;106-B(11):1321–1326.

Aims

This study aims to assess the relationship between history of pseudotumour formation secondary to metal-on-metal (MoM) implants and periprosthetic joint infection (PJI) rate, as well as establish ESR and CRP thresholds that are suggestive of infection in these patients. We hypothesized that patients with a pseudotumour were at increased risk of infection.

Aims. Tuberculosis (TB) infection of bones and joints accounts for 6.7% of TB cases in England, and is associated with significant morbidity and disability. Public Health England reports that patients with TB experience delays in diagnosis and treatment. Our aims were to determine the demographics, presentation and investigation of patients with a TB infection of bones and joints, to help doctors assessing potential cases and to identify avoidable delays. Patients and Methods. This was a retrospective observational study of all adults with positive TB cultures on specimens taken at a tertiary orthopaedic centre between June 2012 and May 2014. A laboratory information system search identified the patients. The demographics, clinical presentation, radiology, histopathology and key clinical dates were obtained from medical records. Results. A total of 31 adult patients were identified. Their median age was 37 years (interquartile range (IQR): 29 to 53); 21 (68%) were male; 89% were migrants. The main sites affected were joints (10, 32%), the spine (8, 26%) and long bones (6, 19%); 8 (26%) had multifocal disease. The most common presenting symptoms were pain (29/31, 94%) and swelling (26/28, 93%). ‘Typical’ symptoms of TB, such as fever, sweats and weight loss, were uncommon. Patients waited a median of seven months (IQR 3 to 13.5) between the onset of symptoms and referral to the tertiary centre and 2.3 months (IQR 1.6 to 3.4.)) between referral and starting treatment. Radiology suggested TB in 26 (84%), but in seven patients (23%) the initial biopsy specimens were not sent for mycobacterial culture, necessitating a second biopsy. Rapid Polymerase Chain Reaction-based testing for TB using Xpert MTB/RIF was performed in five patients; 4 (80%) tested positive for TB. These patients had a reduced time between the diagnostic biopsy and starting treatment than those whose samples were not tested (median eight days versus 36 days, p = 0.016). Conclusion. Patients with bone and joint TB experience delays in diagnosis and treatment, some of which are avoidable. Maintaining a high index of clinical suspicion and sending specimens for mycobacterial culture are crucial to avoid missing cases. Rapid diagnostic tests reduce delays and should be performed on patients with radiological features of TB. Cite this article: Bone Joint J 2018;100-B:119–24

Aims

Histology is widely used for diagnosis of persistent infection during reimplantation in two-stage revision hip and knee arthroplasty, although data on its utility remain scarce. Therefore, this study aims to assess the predictive value of permanent sections at reimplantation in relation to reinfection risk, and to compare results of permanent and frozen sections.

Aims

Fungal periprosthetic joint infections (PJIs) are rare, but their diagnosis and treatment are highly challenging. The purpose of this study was to investigate the clinical outcomes of patients with fungal PJIs treated with two-stage exchange knee arthroplasty combined with prolonged antifungal therapy.