Aim. In 10% of the presumed aseptic hip or knee revisions, a low-grade infection is unexpectedly diagnosed based on the tissue samples taken during revision. Extended antimicrobial prophylaxis can possibly reduce the failure rate in cases of unexpected PJI, because the prophylaxis can be considered as early empiric treatment. In this randomized controlled study we analysed whether extended antimicrobial prophylaxis compared to a single dose is beneficial to improve the outcome of treatment in unexpected PJI in revision arthroplasty. Method. This study was nested in a randomized clinical trial comparing single-dose cefazolin with prolonged prophylaxis (15 doses of cefazolin over 5 days) for revision arthroplasty of the hip or knee. For this analysis, patients were included if an unsuspected PJI (defined as ≥2 positive intraoperative tissue samples with the same microorganism) was diagnosed. PJI treatment consisted of 12 weeks of a rifampicin-based regimen in Staphylococcal PJI, without removal of the prosthesis. We examined Infection characteristics and success of treatment after one year, defined as the absence of signs or treatment for PJI during follow-up. Results. After randomization of 662 patients, 68 unexpected PJI were diagnosed. In 5 cases no antimicrobial treatment was started. The success rate after one year follow-up for those who received PJI treatment was 96% (28/29) in the single dose group and 91% (31/34) in the extended prophylaxis group (p=1.00). The most frequently identified pathogens in unexpected PJI were Cutibacterium acnes (n=50) and Staphylococcus epidermidis (n=14). The causatives were susceptible for the cefazolin prophylaxis in 61 of the 63 cases. The interval between the stopped prophylaxis and the re-start of antimicrobial treatment was on average 10 days (SD 4) for the single dose and 5 days (SD 4) for the extended group. The mean duration of antimicrobial treatment was 83 days (SD 12) and did not differ between both groups (p=0.16). Conclusions. This is the first randomized controlled trial in which extended prophylaxis showed no benefit on the prosthesis survival for patients with an unexpected PJI after assumed aseptic revision of the hip or knee prosthesis. The results imply that extended prophylaxis should not be given as part of early empiric therapy

Aim. Perioperative myocardial infarction/injury (PMI) is a common complication in noncardiac surgery, contributing to postoperative morbidity and mortality. We aimed to identify the risk for PMI in periprosthetic joint infection (PJI) in comparison to primary hip (THA) and knee arthroplasty (TKA) and to non-PJI revision surgery. Methods. Patients undergoing primary/revision THA/TKA at a University Hospital who were eligible for the institutional PMI screening and response program were prospectively included. Revision arthroplasties were divided into 2 groups (PJI revision and non-PJI revision). PJI was defined according to the EBJIS criteria, and included DAIR, one-stage and two-stage revisions. Non-PJI revisions included partial and/or complete exchange of components. The primary endpoint was PMI, secondary endpoints were major adverse cardiovascular events (MACE) and all-cause mortality within 120 days. Results. The study population included 673 patients (443 primary THA/TKA, 119 PJI revision, 111 Non-PJI revision) enrolled from 05/2014 to 06/2018. The median age in all groups was 75 years. In primary, non-PJI and PJI revision surgery, 39%, 41% and 50%, respectively were male. PMI occurred in 12% of patients with primary arthroplasty compared to 20% and 35% in non-PJI and PJI revision, respectively (p<0.001 overall), with PJI having a significantly elevated risk over non-PJI revisions (p=0.014). Conversely, in MACE (4% primary vs 9% non-PJI vs 12% PJI, p=0.002) an all-cause mortality (2% primary vs 4% non-PJI vs 9% PJI, p<0.001) no significant difference between PJI and non-PJI revisions was observed. We found no difference for the risk of PMI comparing DAIR vs one-/two-stage PJI revision (p=0.88). In multivariable analysis (primary arthroplasty as reference), significant odds ratios for PMI included PJI (3, 1.7–5.3), coronary artery disease (2.9, 1.9–4.4), chronic heart faiure (1.3, 1.1–1.7) and age (1.1, 1.0–1.1 per each year age). Urgency of surgery, duration of surgery, to the presence of Staphylococcus aureus were not significant. impact on PMI. Conclusion. In PJI, PMI and MACE were 3-times, and death 4.5 times, respectively, more frequently observed than in primary arthroplasty. Also, PJI had the highest odds for PMI (3.0). Orthopaedic surgeons should be aware of the high PMI risk when performing revision surgery. This work confirms the importance of a peri-/postpoperative PMI screening and response program in the field of septic surgery

Aims. To explore the effect of different durations of antibiotics after stage II reimplantation on the prognosis of two-stage revision for chronic periprosthetic joint infection (PJI). Methods. This study involved a retrospective collection of patients who underwent two-stage revision for chronic PJI and continued to use extended antibiotic prophylaxis in two regional medical centres from January 2010 to June 2018. The patients were divided into a short (≤ one month) or a long (> one month) course of treatment based on the duration of antibiotics following stage II reimplantation. The difference in the infection control rate between the two groups was compared, and prognostic factors for recurrence were analyzed. Results. A total of 105 patients with chronic PJI were enrolled: 64 patients in the short course group and 41 patients in the long course group. For 99 of the patients, the infection was under control during a follow-up period of at least 24 months after two-stage revision. For the short course group, the mean duration of antibiotic prophylaxis after stage II reimplantation was 20.17 days (SD 5.30) and the infection control rate was 95.3%; for the long course group these were 45.02 days (SD 15.03) and 92.7%, respectively. There was no significant difference in infection control rates between the two groups (p = 0.676). Cox regression analysis found that methicillin-resistant staphylococcus infection (p = 0.015) was an independent prognostic factor for recurrence. Conclusion. After stage II reimplantation surgery of two-stage revision for chronic PJI, extended antibiotic prophylaxis for less than one month can achieve good infection control rate. Cite this article: Bone Joint Res 2021;10(12):790–796

Prosthetic joint infection (PJI) is a complex disease that causes significant damage to the peri-implant tissue. Developing an animal model that is clinically relevant in depicting this disease process is an important step towards developing novel successful therapies. In this study, we have performed a thorough histologic analysis of peri-implant tissue harvested post Staphylococcus aureus (S. aureus) infection of a cemented 3D-printed titanium hip implant in rats. Sprague-Dawley rats underwent left hip cemented 3D-printed titanium hemiarthroplasty via posterior approach under general anesthesia. Four surgeries were performed for the control group and another four for the infected group. The hip joint was inoculated with 5×10. 9. CFU/mL of S. aureus Xen36 prior to capsule closure. The animals were scarified 3 weeks after infection. The femur was harvested and underwent micro-CT and histologic analysis. Hematoxylin and eosin (H&E), as well as Masson's trichrome (MT) stains were performed. Immunohistochemistry (IHC) using rabbit antibody for S. aureus was also used to localize bacterial presence within femur and acetabulum tissue . The histologic analysis revealed strong resemblance to tissue changes in the clinical setting of chronic PJI. IHC demonstrated the extent of bacterial spread within the peri-implant tissue away from the site of infection. The H&E and MT stains showed 5 main features in infected bone: 1) increased PMNs, 2) fibrovascular inflammation, 3) bone necrosis, and 4) increased osteoclasts 5) fibrosis of muscular tissue and cartilage. Micro CT data showed significantly more osteolysis present around the infected prosthesis compared to control (surgery with no infection). This is the first clinically relevant PJI animal model with detailed histologic analysis that strongly resembles the clinical tissue pathology of chronic PJI. This model can provide a better understanding of how various PJI therapies can halt or reverse peri-implant tissue damage caused by infection

Aim. To describe the impact of a failed DAIR in the further prognosis of the prosthesis after a PJI. Method. A retrospective multicentrically study was conducted, including 10 institutions from all over the country. PJI-confirmed patients who underwent DAIR clinical records were revised. Age, sex, relevant previous conditions, Charlson comorbidity score, previous surgery, PJI diagnosis and surgical and antibiotic treatment, from the index surgery onwards. DAIR failure was defined as the removal of the prosthesis and/or an antibiotic suppressive treatment. Results. 95 failed DAIR were identified, 43 of whom were treated with another DAIR (70% success rate), 20 with one-stage revision (75% success rate) and 25 with two-stage revision (92% success rate). As risk factors for the failure of a second DAIR, a non-specialized surgical team(p=.0034), mobile components exchange(p=.009) and polymicrobial infections(p=.03) were identified. Regarding to one-stage revisions, no risk factors were identified, and regarding to two-stage revisions, polymicrobial infection were identified (p=.028). Conclusions. A second DAIR could sabe up to 70% of the prosthesis in our series. Furthermore, the outcome of the subsequent one or two-stage revision does not seem to be affected bay the previous failed DAIR. In terms of risk factors of failure, non-specialized surgical team, no mobile components exchange, and polymicrobial infections were identified for the DAIR, and polymicrobial infections for the two-stage revisions

Introduction. Debridement, antibiotics irrigation and implant retention (DAIR) is a common management strategy for hip and knee prosthetic joint infections (PJI). However, failure rates remain high, which has led to the development of predictive tools to help determine success. These tools include KLIC and CRIME80 for acute-postoperative (AP) and acute haematogenous (AH) PJI respectively. We investigated whether these tools were applicable to a Waikato cohort. Method. We performed a retrospective cohort study that evaluated patients who underwent DAIR between January 2010 and June 2020 at Waikato Hospital. Pre-operative KLIC and CRIME80 scores were calculated and compared to success of operation. Failure was defined as: (i) need for further surgery, (ii) need for suppressive antibiotics, (iii) death due to the infection. Logistic regression models were used to calculate the area under the curve (AUC). Results. 117 eligible patients underwent DAIR, 53 in the AP cohort and 64 in the AH cohort. Failure rate at 2 years post-op was 43% in the AP cohort and 59% in the AH cohort. In the AP cohort a KLIC score of <4 had a DAIR failure rate of 28.6%, while those who scored ³4 had a failure rate of 72.2% (p=0.002). In the AH cohort a CRIME80 score of <3 had a DAIR failure rate of 48% while those who scored ³3 had a 100% failure rate (p<0.001). Discussion. This study represents the first external validation of the KLIC and CRIME80 scores for predicting DAIR failure in an Australasian population. The results indicate that both KLIC and CRIME80 scoring tools are valuable aids for the clinician seeking to determine the optimal management strategy in patients with AP or AH PJI

Periprosthetic joint infection (PJI) in geriatric and/or multimorbid patients is an enormous challenge for orthopaedic surgeons. Revision procedures have also been demonstrated to expose patients to higher infection risks. Prior patient stratification according to presumed infection risks, followed by a more potent local antibiotic prophylaxis protocol with selective use of DALBC, is an interesting strategy to decrease the burden of PJI in high risk patients. The PubMed & EMBASE databases were screened for publications pertaining to the utilization of DALBC in cement for infection prophylaxis & prosthesis fixation. 6 preclinical & 7 clinical studies were identified which met the inclusion criteria and were stratified by level of clinical evidence. Only those studies were considered which compared the PJI outcome in the DALBC vs the SALBC group. (1). DALBC have been shown to exert a much stronger and longer lasting inhibition of biofilm formation on many PJI relevant bacteria (gram-positive and gram-negative pathogens) than single gentamicin-only containing cements. (2). DALBC use (COPAL G+C) in the intervention arm of 7 clinical studies has led to a significant reduction of PJI cases in a) cemented hemiarthroplasty procedures (3 studies, evidence level I and III), in b) cemented septic revision surgeries (2 studies, evidence level III), in c) cemented aseptic knee revisions (1 study, evidence level III) and in d) cemented primary arthroplasties in multi-morbid patients (1 study, evidence level III-IV). These benefits were not associated with more systemic side effects or a higher prevalence of broad antimicrobial resistancies. Use of DALBC is likely to be more effective in preventing PJI in high risk patients. The preliminar findings so far may encourage clinicians to consolidate this hypothesis on a wider clinical range

Historical perspective: Irrigation and debridement (I&D) with modular exchange has historically been the recommended treatment for acute post-operative periprosthetic joint infection (PJI), and acute hematogenous PJI. The theory supporting this practice was that because the bacterial glycocalyx had not yet formed by these early time points, by simply debriding the intra-articular bacterial load and exchanging the modular parts, one could potentially eradicate the infection, retain the prior components, and minimise morbidity to the patient. More recently, literature is coming out suggesting that this may not necessarily be the case. The vast majority of published research on the outcomes following I&D for treatment of PJI has focused on either cohorts of total knee arthroplasty patients or combined cohorts of total hip and knee patients. For this reason, it is difficult to tease out the differential success rate of periprosthetic hip vs. knee infections. Sherrell et al. performed a systematic review of the existing literature and created a table detailing the failure rates for various published articles on I&D for periprosthetic TKA infection. Since it is the glycocalyx that has been thought to be the reason for treatment failure of many cases of PJI treated with I&D, many authors have implicated staphylococcal species as a predictor of a negative outcome with failure rates ranging from 30–35%. Methicillin resistant organisms have been shown to be particularly difficult to eradicate with an isolated I&D, with a 72–84% failure rate at 2 year follow-up. Interestingly, a recent study by Odum et al. suggests that neither the infecting microbe, nor the antibiotic resistance profile of the organism, as has been classically thought, actually predicts success of I&D. Previous reports have indicated that the ability of I&D to control infection is related to the duration of symptoms and its timing relative to the index surgery. However, more recent literature is coming out to support the contrary. Koyonos et al. reviewed the outcomes of a series of 138 cases of PJI treated with I&D based on acuity of infection and concluded that an I&D has a limited role in controlling PJI regardless of acuity. Intuitively, the physical health of the host/patient should influence the success of I&D for treatment of PJI. Several authors have shown that an immunocompromised state is a predictor of treatment failure. Furthermore, Azzam et al. reported that patients with a higher American Society of Anesthesia (ASA) score, a proxy of severity of medical comorbidities, had a significantly higher failure rate. Although potentially appealing due to relative ease of execution and minimal surgical morbidity, the ability to successfully eradicate infection with an arthroscopic procedure may be compromised. Given the inability to perform a radical surgical debridement, nor exchange modular components, arthroscopic debridement should be used with extreme reservation in any case of PJI, regardless of the host, nature of the infecting organism, or acuity of infection. I&D as a conservative, less morbid alternative to two-stage exchange - There is a growing body of literature to suggest that an I&D with modular component exchange may not be the benign, less morbid alternative to the ‘gold standard’ two-stage exchange arthroplasty. In fact, Fehring et al. has reported that the success of a two-stage antibiotic spacer exchange arthroplasty may be compromised by an initial I&D. They found that patients who were initially treated with an I&D only had a 66% chance of eradicating infection following a two-stage exchange arthroplasty, in contrast to historical reports of 80–90% success

Introduction. Studies are being done comparing 1-stage vs. 2-stage protocols for PJI. 1-stage protocols take an extended period of time requiring 2 separate preps and sets of instruments in order to ensure optimal sterility. While intraoperative service time is one part of the reimbursement algorithm, reimbursement has lagged behind for single stage treatment. If 1-stage results are acceptable, but not reimbursed appropriately, surgeons may be discouraged from managing PJI in a 1-stage fashion. We ask, “What is the reimbursement and intraoperative service time for 1-stage procedures compared to primary surgery?”. Methods. Relative Value Unit's (RVU's), reimbursement and operative time for 50 PJI procedures were reviewed and compared to 250 primary (1°) THA and 250 primary (1°) TKA by four surgeons. Coding was done per AAOS guidelines. Results. Average work RVU's for 1-stage knees were 19.79 RVU's/hr. vs 23.47 for 1° TKA. Average reimbursement for a 1-stage knee was $2,597.08, with an average intraoperative service time of 259 minutes ($601.60/hr.). Average reimbursement for a 1° TKA was $2,435.00, with an average service time of 100 minutes ($1,461/ hr.). Average work RVU's for a 1-stage hip were 19.57/hr. vs 25.59 for a 1° THA. Average reimbursement for a 1-stage hip was $2,826.17, with an average intraoperative service time of 311 minutes ($545.24/ hr.). The average reimbursement for a 1° total hip was $2,754.71 with an average service time of 104 minutes ($1,589.26/ hr.). Conclusion. While RVUs/hr are similar between primaries and 1-stage procedures, 1-stage procedures for PJI are reimbursed at approximately 1/3 the hourly rate of a primary procedure. This may discourage surgeons from selecting this treatment alternative if studies confirm efficacy. Payers should be encouraged to reimburse physicians commensurate with the intraoperative service time needed to perform a 1-stage procedure as adoption will decrease morbidity and save the healthcare system financially

Introduction. Two-stage exchange arthroplasty remains the gold standard for treatment of PJI with reported success rates of 85–90%. Complications that occur during treatment are often not reported or considered in the success rate. The purpose of this study was to analyze complications in patients undergoing two-stage exchange and determine when they occur. Methods. We analyzed all patients that underwent two-stage exchange arthroplasty for treatment of chronic PJI of the knee from 2010 to 2018. We categorized complications as medical vs. surgical. The intervals for complications were divided into: interstage, early post re-implant (3 months) and late post re-implant (3 months to minimum 1 year). Minimum follow-up to evaluate complications was one year. Results. Overall, 132 patients underwent a first stage of a two-stage exchange. There were 63 males and 59 females with an average age at first stage surgery of 66.6 years (SD: 8.9). Ten patients (7.6%) did not undergo re-implantation following resection arthroplasty (8 retained spacers and 2 deaths). 122 patients underwent the planned second stage of a two-stage exchange arthroplasty of the knee. The overall success rate (re-implant without recurrence of infection) was 78%. Overall mortality was 1.6% at one year and 9% at 5 years after treatment. Fifty-six patients (46%) experienced at least one complication. 43 patients had an orthopaedic related complication that required additional surgery and 13 patients had a medical complication. 33% of the total complications occurred during the interstage period, 18% within 90 days of reimplant, and 37% greater than three months from reimplant (p=0.0287). Discussion. Reported rates of success of two stage exchanges for PJI have not traditionally considered complications in the definition of success. In our series, significant numbers of patients experienced complications, more often after reimplantation, highlighting the morbidity of this method of treatment and the need for in-depth patient counseling, careful surgical technique, and close follow up. For figures, tables, or references, please contact authors directly

Introduction. Debridement, Antibiotics and Implant Retention (DAIR) remains the norm for the treatment of acute periprosthetic joint infection (PJI) despite less than optimal success rates. Intraosseous (IO) administration of vancomycin has been shown to have significantly increased local bone and tissue concentrations compared to systemic antibiotics, with lower systemic antibiotic levels compared to intravenous. The purpose of this study was to evaluate if the addition of IO regional antibiotics to our protocol at the time of DAIR would improve outcomes. Methods. A retrospective review of 35 PJI TKA patients who underwent DAIR combined with IO vancomycin (500mg) was performed with minimum 12-month follow-up. 26 patients were treated for acute perioperative or acute hematogenous infections following primary TKA. Nine were treated for chronic infections with components that were considered unresectable (ie) constructs with ingrown cones, sleeves, or long cemented stems in elderly comorbid patients. Primary outcome was defined by no reoperations for infection nor clinical signs or symptoms of PJI. Results. The average follow up for acute infection was 16.5 months (range 12.1–24.2) and 15.8 months (range 12–24.8) for chronic infections with unresectable components. Overall eradication rates for acute infection was 93.1% while only 44.4% for chronic infections with unresectable components. MSIS host grade was a significant indicator of failure (p<0.001). Conclusion. The use of IO vancomycin at the time of DAIR yielded improved results compared to standard irrigation and debridement in acute periprosthetic infections. Its use in chronic infections should remain cautious. While these results are encouraging, this technique requires longer follow-up before widespread adoption

Prosthetic joint infections (PJI) are caused by a variety of microorganisms but most frequently by staphylococci. The results of treatment of PJI due to organisms other than staphylococci are less known. The aim of this study is to evaluate the outcomes after streptococcal PJI. The data of 26 streptococcal (13 hip and 13 knee PJI from 24 patients) were retrieved from hospital based PJI register, and analyzed. There were 15 female and 11 male patients (mean age 66 y). Most (13) PJI were hematogenous. 15 PJI had been treated with debridement and retention (D&R) of the infected joint, 1 with permanent resection arthroplasty, 9 had two stage revision and 1 patient had one stage partial replacement. After the microbiological diagnosis was established most patients received 2–3 weeks of penicillin G or ceftriaxone followed by 2–6 months of oral amoxicillin. All patients had regular follow-ups after the procedure at least at 1 month, three months and one year. The results were classified as: PJI cure (in absence of clinical signs and symptoms of infection and with negative CRP), probable failure (in absence of clinical signs and symptoms of infection but with elevated CRP), definite failure (if a new treatment was necessary), and mechanical failure (aseptic loosening, periprosthetic fracture, quadriceps rupture). One foreign patient was lost to follow up. The mean follow up time for the rest was 60 months (from 16 to 167) months. There was probable prosthesis failure in 1 case, definite prosthesis failure in 7 cases and mechanical failure in 3 cases. The mean survival time of the failed prostheses was 28 (range from 2 to 83) months. 6 failures (40 %) occurred in group of cases that had undergone D&R, and 1 (6 %) in the two stage revision group. Among the 7 definite failures in 4 patients antibiotic treatment was empirically started after the symptoms reappeared resulting in long remission periods. Comparing to the published results of staphylococcal PJI it seems that D&R of the prosthesis for streptococcal PJI is considerably less successful. Rifampicin as a proven treatment of choice for staphylococcal infections is probably the main reason for the difference. An unexpected feature of streptococcal PJI is that definite failures are easily suppressed for long time with a short course of oral antibiotics

Aim. A key of success in the treatment of prosthetic joint infection (PJI) is the proper diagnosis. There is a lack of diagnostic tools able to diagnose a PJI with high accuracy. Alpha-defensin has been proposed as possible solution but the available literature is still limited. This prospective study was carried out in order to determine (1) what is the sensitivity, the specificity, the positive and the negative predictive value of the Alpha-defensin immunoassay test in diagnosing PJI; (2) which clinical features may be responsible for false positive and false negative results?. Method. Preoperative aspiration was performed in patients presenting with a painful hip/knee arthroplasty. Metallosis, other inflammatory comorbidities and previous/concomitant antibiotic therapy were not considered as exclusion criteria. Patients with inadequate amount of synovial fluid for culture were excluded. At time of revision synovial fluid samples were taken in the OR in order to perform Alpha-defensin assay. During surgical debridement tissue samples for cultures were obtained. Prospectively, 156 patients (65 knees and 91 hips) were included. A diagnosis of PJI was confirmed in 29 patients. Results. The sensitivity of the Alpha-defensin immunoassay was 97% (95% CI, 92% – 99%), the specificity was 97% (95% CI, 92% – 99%), the positive predictive value was 88% (95% CI, 81% – 92%) and the negative predictive value was 99% (95% CI, 96% – 99%). Among four false positive patients two had a metallosis and one had a polyethylene wear. The false negative case presented with a draining sinus, and intraoperative cultures were also negative. Conclusions. Alpha-defensin assay may have a significant role in PJI diagnosis. Negative tests may exclude the diagnosis of PJI. Positive tests are very much likely to confirm PJI, but other conditions (metallosis, poly wear) should be excluded

While advances in laboratory and imaging modalities facilitate the diagnosis of periprosthetic joint infection (PJI), clinical suspicion and a thorough history and physical remain the basis of evaluation. If clinical suspicion is high, the evaluation should be more vigorous, and vice versa. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are inexpensive as well as ubiquitous, and should be obtained as a preliminary screening tool. These tests have been found to be cost-effective and highly sensitive. If both tests are negative, there is a low risk of periprosthetic joint infection (i.e., good negative predictive value). Positive results on both tests, in contrast, are not as specific but again raise suspicion. When either the ESR or CRP is elevated, or if the clinical suspicion for infection is high, aspiration of the knee joint is suggested. Synovial fluid should be sent for a synovial fluid white blood cell count (WBC), differential and culture. Given the ability to get three data points from one intervention, arthrocentesis, is the best single maneuver the physician can perform to rule in or out PJI. The synovial fluid WBC count has demonstrated in multiple studies excellent specificity and sensitivity in the diagnosis of infection. Based on multiple recent studies, the proceedings of the International Consensus on PJI recommend cut-offs for the synovial fluid WBC count as >3000 cells/mL and > 80% neutrophils for the differential. Synovial fluid biomarkers represent an expanding area of clinical interests based on the unique cascade of gene expression that occurs in white blood cells in response to pathogens. Deirmegian et al. described the unique gene expression and biomarker production by neutrophils in response to bacteria that are detectable in synovial fluid. Specifically, alpha-defensin is one such antimicrobial peptide. Along with synovial CRP, alpha-defensin can be measured in a currently commercially-available immunoassays. The diagnosis of PJI can be difficult to make in spite of the variety of tests available. That being said, the diagnosis is easily made in our experience in 90% of patients by getting an ESR and CRP followed by selective aspiration of the joint if these values are elevated or if the clinical suspicion is high. Synovial fluid obtained should be sent for a synovial fluid WBC count, differential and cultures

Aim. Prosthetic joint infection (PJI) is a major complication in THA. Nasal carriage with S. Aureus is a well-defined risk factor for infection in hospitalized patients. Risk for infection is reduced up to 50% by eradication therapy. Since PJI rates are very low and only 25% of the population are carriers, significant differences are hard to show and reports on PJI have been inconclusive. We analysed the effect of S. Aureus eradication therapy in THA. Methods. From 2011, patients receiving THA are screened for S. Aureus carriage and carriers are treated. This group was retrospectively compared with a historical THA group in which no screening and eradication therapy was done. We assumed similar carrier rates in both groups and calculated the risk reduction of eradication therapy for PJI in comparison to the historical carriers without treatment. Fisher's Exact test was used to compare outcome. Results. 2072 patients were screened and 478 patients were positive (23%). The historical control group consisted of 1248 patients, with 288 calculated carriers (23%). 15 PJI (0.72%) occurred vs 14 (1.12%) in the historical group (p=0.16). A 52% reduction in S. Aureus infections was found (0.33% vs 0.64% p=0.15). Infection rates for PJI caused by S. aureus was similar in non-carriers and carriers after eradication therapy (0.3 vs 0.4% p=0.506). The calculated infection rates in carriers in the historical group was reduced from 2.6% to 0.8% (RR 3,25, p=0.07) by eradication therapy and from 1.7% to 0,4% (RR 4,25, p=0.07) for S. Aureus PJI. Conclusions. A clear trend in reduction of PJI was demonstrated as a result of S. aureus screening and eradication therapy, reducing the rate of PJI for carriers to the same level as non-carriers

Aim. Perioperative hyperglycemia has many etiologies including medication, impaired glucose tolerance, uncontrolled diabetes mellitus (DM), or stress, the latter of which is common to post-surgical patients. This acute hyperglycemia may impair the ability of the host to combat infection. 1. Our study aims to investigate if post-operative day 1 (POD1) blood glucose level is associated with complications, including periprosthetic joint infection (PJI), after total joint arthroplasty (TJA) and to determine a threshold for glycemic control that surgeons should strive for during a patient's hospital stay. Method. A single-institution retrospective review was conducted on 24,857 primary TJAs performed from 2001–2015. Demographics, Elixhauser comorbidities, laboratory values, complications and readmissions were collected. POD1 morning blood glucose levels were utilized and correlated with PJI, as defined by the Musculoskeletal Infection Society criteria. The Wald test was used to determine the influence of covariates on complication rate. An alpha level of 0.05 was used to determine statistical significance. Results. The rate of PJI significantly increased linearly from blood glucose levels of 115 mg/dL onwards. We determined that blood glucose (OR 1.004, 95% CI: 1.001–1.006, p=0.001), male gender (OR 1.480, 95% CI: 1.185–1.848, p=0.001), body mass index (OR 1.049, 95% CI: 1.033–1.065, p<0.001), operative time (OR 1.004, 95% CI: 1.001–1.007, p=0.006), length of stay (OR 1.059, 95% CI: 1.038–1.080, p<0.001), post-operative hematocrit (OR 0.751, 95% ci: 0.621–0.909, p=0.003), peripheral vascular disease (OR 1.942, 95% CI: 1.042–3.617, p=0.037), liver disease (OR 2.576, 95% CI: 1.344–4.935, p=0.004), rheumatic disease (OR 1.991, 95% CI: 1.266–3.132, p=0.003), and alcohol abuse (OR 2.588, 95% CI: 1.096–6.110, p=0.030) were associated with PJI. The Youden index was used to determine an optimal blood glucose threshold of 132 mg/dL to reduce the likelihood of PJI. The PJI rate in the entire cohort was 1.59% (1.46% in non-diabetics compared to 2.39% in diabetics, p=0.001). Diabetics did not have an association between blood glucose level and PJI (OR 1.002, 95% CI: 0.998–1.006, p=0.331), although there was a linear trend for postoperative glucose predicting PJI. Conclusions. The relationship between POD1 blood glucose levels and PJI increased linearly, with an optimal cut off of 132 mg/dL. Immediate and strict post-operative glycemic control is critical in reducing post-operative complications, and we demonstrate that even mild hyperglycemia is significantly associated with PJI

Introduction. Periprosthetic joint infection (PJI) is considered one of the most feared causes of implant failure, due to the difficulty in formulating a proper and timely diagnosis. In the diagnostic workup are often used test with a low specificity, such as the dosage of ESR and CRP, or sensitivity, such as cultures or the leukocyte count of the synovial fluid. Radiological investigations are expensive and unreliable to play a direct role in the diagnosis of PJI. The alpha-defensin is an antimicrobial peptide released by neutrophils in response to pathogens and it is an ideal biomarker for the diagnosis of PJI. It is now possible to verify the presence of alpha-defensin in periprosthetic synovial fluid with an ELISA (Synovasure® PJI, Zimmer) that provides results in 10 minutes, with a sensitivity of 97% and a specificity of 96%, without being affected by systemic inflammatory diseases or by the assumption of antibiotics. The purpose of this study is to assess the applicability and reliability of Synovasure® PJI, correlating its results with microbiological analyzes, laboratory tests and imaging studies of the patient. Materials and Methods. Patients recruited are those who have undergone a previous total hip or knee arthroplasty where there is suspicion of PJI. The test can be performed either during surgery or during the diagnostic iter, through the execution of an arthrocentesis. The synovial fluid is partly used for Synovasure® PJI and partly put in culture for microbiological analyzes. Once ready, culture results are compared with the results of the test to get a confirmation of its reliability or reference to identify the microorganism responsible for PJI. These data are then compared, with laboratory tests and radiological investigations performed by the patient. Results. Up to now we have full results in 10 patients (11 implants). In four cases, the test showed the presence of alpha-defensin in the synovial fluid, while in seven cases the test result were negative. In case of negative test culture of synovial fluid showed no growth of microorganisms that could indicate the presence of false negatives. All patients with positive test have arthrocentesis positive for pathogenic microorganisms. We are waiting for culture results of two other patients (one with positive test and one with negative test). In the next few months will be tested other patients with suspicion of PJI. Discussion. Timeliness and accuracy in the diagnosis are essential for the proper management of the patient with suspected PJI. Diagnostic tools currently available are often sensitive but not very specific or conversely, specific but insensitive. New synovial markers such as alpha-defensin and rapid ELISA tests for their dosage open new horizons in the diagnosis of periprosthetic infections. Conclusions. Synovasure® PJI is a practical and reliable tool in the diagnosis of periprosthetic joint infections. Thanks to the quick response and the ease of execution the test can be used both during the diagnostic iter and during the revision surgery helping the orthopedic to apply the most appropriate measures to each case

Prosthetic joint infection (PJI) is a serious complication following joint replacement. Antiseptic solutions are often used for intraoperative wound irrigation particularly in cases of revision for PJI. Antiseptic irrigation is intended to eradicate residual bacteria which may be either free floating or in residual biofilm although there is no clear clinical efficacy for its use. Also, reviewing the scientific literature there is discordance in in vitro results where some studies questions antiseptic efficacy whilst others suggest that even at low concentration antiseptic agents are effective at eradicating bacterial biofilms. The aim of this in vitro study was to establish the efficacy of undiluted antiseptic agents at eradication of a typical PJI forming biofilm and determine the importance of an antiseptic neutralisation step in this assessment. Mature Staphylococcus epidermidis biofilms grown on TiAl6V4 discs were submerged in chlorohexidine (CHL) gluconate 4%, povidone-iodine (PI) 10% or phosphate-buffered saline (PBS) control solution. The discs were then rinsed, the biofilm bacteria suspended in solution using sonication and vortexing, and the viable count (CFU/ml) of the bacterial suspensions determined. The rinse/suspension solution was either (a) PBS or (b) Dey-Engley neutralization broth (NB). When PBS was used to rinse/suspend the biofilm a highly significant, 7.5 and 4.1, mean log reduction in biofilm vitality was observed from the control, for CHL 4% and PI 10%, respectively. However, when NB was the rinse/suspension solution the apparent antiseptic biofilm eradication efficacy was replaced with a statistically significant but clinically irrelevant less the one log-reduction in biofilm vitality. Clinical antiseptic agents are ineffective at eradicating S. epidermidis biofilm in an in vitro PJI model and absence of a neutralisation step gives the false impression of efficacy. Antiseptics alone are an ineffective treatment for biofilm related PJI and no substitute for meticulous debridement

Aims. The aim of this study was to evaluate the diagnostic accuracy of the absolute synovial polymorphonuclear neutrophil cell (PMN) count for the diagnosis or exclusion of periprosthetic joint infection (PJI) after total hip (THA) or knee arthroplasty (TKA). Methods. In this retrospective cohort study, 147 consecutive patients with acute or chronic complaints following THA and TKA were included. Diagnosis of PJI was established based on the 2018 International Consensus Meeting criteria. A total of 39 patients diagnosed with PJI (32 chronic and seven acute) and 108 patients with aseptic complications were surgically revised. Results. Using receiver operating characteristic curves and calculating the area under the curve (AUC), an optimal synovial cut-off value of 2,000 PMN/µl was determined (AUC 0.978 (95% confidence interval (CI) 0.946 to 1)). Using this cut-off, sensitivity and specificity of absolute synovial PMN count for PJI were 97.4% (95% CI 91.2 to 100) and 93.5% (95% CI 88.9 to 98.1), respectively. Positive and negative predictive value were 84.4% (95% CI 72.7 to 93.9) and 99.0% (95% CI 96.7 to 100), respectively. Exclusion of 20 patients with acute complications improved specificity to 97.9% (95% CI 94.6 to 100). Different cut-off values for THA (< 3,600 PMN/µl) and TKA (< 2,000 PMN/µl) were identified. Absolute synovial PMN count correlated strongly with synovial alpha-defensin (AD) (r = 0.759; p < 0.001). With a positive AD result, no additional PJI could be identified in any case. Conclusion. Absolute synovial PMN count is a widely available, rapid, cost-effective, and accurate marker in PJI diagnostics, whereas synovial AD appears to be a surrogate parameter of absolute synovial PMN count. Despite limitations in the early postoperative phase, wear, and rheumatic diseases in confirming PJI, an absolute synovial PMN count below 2,000/µl is highly suitable for ruling out PJI, with specific cut-off values for THA and TKA. Cite this article: Bone Joint J 2023;105-B(4):373–381

Introduction. Sonicate fluid cultures (SFC) are more sensitive than conventional microbiological methods in identifying periprosthetic joint infections (PJI), because sonication enables a sampling of the causative bacteria directly from the surface of the endoprosthetic components. Because of their high sensitivity SFC can be positive while all other microbiological methods remain negative. It is therefore difficult to interpret a single SFC as being truly or falsely positive. The aim of this prospective study was to improve the interpretation of SFC in the diagnosis of PJI in patients after total hip arthroplasty through the use of multiple SFC. Material and methods. 102 patients of which 37 had a defined PJI according to the following criteria were included: intraarticular pus or a sinus tract, a periprosthetic membrane (PM) indicative of infection, or a positive microbiological culture in a minimum of 2 separate microbiological samples. A single positive microbiological sample was classified as false positive. In 35 patients multiple SFC were acquired from the separate endoprosthetic components. Results. Out of all individual diagnostic parameters SFC achieved the highest sensitivity with 89% and a specificity of 72%. PM was able to achieve a sensitivity of 78% for the detection of PJI. Out of the 35 patients with multiple SFC it was possible to newly diagnose a PJI in 3 cases solely through multiple isolations of the same bacterial species in SFC. In the same group it was also possible to exclude the suspicion of PJI in 3 cases, because only one of the multiple samples presented a bacterial isolation, while the other samples remained negative. When multiple SFC were employed it was possible to increase the sensitivity to 100% and the specificity to 85%. Conclusion. In our study SFC were the most sensitive diagnostic parameter for detection of PJI and our results show that it is possible to further increase the sensitivity and specificity of SFC when multiple samples are used. The acquisition of multiple SFC facilitate the diagnosis of PJI, since they are able to present the 2 positive bacterial isolations that are needed for making the diagnosis of PJI. Multiple SFC can help to solve the orthopaedic surgeon's diagnostic dilemma of having to interpret a single positive bacterial isolation by confirming the bacterial isolation in a second SFC sample

Background. Exebacase, an antistaphylococcal lysin in Phase 3 of development as a treatment for S. aureus bacteremia/right-sided endocarditis has demonstrated antibiofilm activity in vitro and has previously been used as salvage therapy in four patients with relapsing multidrug-resistant (MDR) S. epidermidis knee prosthetic joint infection (PJI) using a procedure called LysinDAIR (administration of the lysin during the performance of an arthroscopic DAIR). Materials/methods. We performed a single center, exploratory, open-label prospective study using the LysinDAIR procedure in patients with chronic (inoculation >3 months prior to treatment) coagulase-negative staphylococci (CNS) PJI of the knee with two different clinical presentations and treatment paradigms. Cohort A: first episode of CNS knee PJI, for whom the LysinDAIR was followed by clindamycin + levofloxacin planned to be prescribed for three months and then stopped; and Cohort B: relapsing episodes of MDR CNS knee PJI for whom the LysinDAIR was followed by primary antimicrobial therapy for three months, followed by suppressive antimicrobial therapy (SAT). Exebacae susceptibility testing was performed before treatment for each patient. In agreement with the French Health authority, exebacase (2 to 3.5 total mg in 30–50 ml (∼0.067 – 0.075 mg/m) was administered directly into the joint during arthroscopy. Results. Eight patients were treated. Exebacase administration was well tolerated by all patients and no serious adverse drug reactions to exebacase were reported. In cohort A (n=4), patients had susceptible S. epidermidis PJI, a painful joint effusion without fistula and without loosening, and received three months of levofloxacin + clindamycin (one patient received an alternative regimen following antibiotic adverse events) and then antibiotics were stopped. During a follow-up of 14, 19, 26 and 36 months, no relapse, no recurrence of the joint effusion and no loosening occurred. In cohort B (n=4), patients had MDR CNS, clinical signs of septic arthritis with a joint effusion without fistula and without loosening and received daptomycin + linezolid or doxycycline. One patient died from COVID-19 at week 4. SAT (tedizolide, n=2; doxycycline, n=1) was then prescribed to other patients. One experienced an infection relapse involving S. caprae under tedizolid therapy at six months. The two other patients continue to do well under SAT 8 and 12 months after the LysinDAIR procedure. Conclusions. The LysinDAIR procedure is a minimally invasive procedure, which has been shown to be easy-to-perform, safe, and has the potential for use as initial treatment or salvage therapy in patients with CNS chronic knee PJI

Introduction. There is no literature regarding the risk of a patient developing PJI after primary TKA if the patient has previously experienced PJI of a TKA or THA in another joint. The goal of this study was to compare the risk of PJI of primary TKA in this patient population compared to matched controls. Methods. We retrospectively reviewed 95 patients (102 primary TKAs) from 2000–2014 with a history of a TKA or THA PJI in another joint. Mean age was 69 years; mean BMI was 36 kg/m2. 27% high-risk patients were on chronic antibiotic suppression. Mean follow-up was 6 years. We 1:3 matched (to age, sex, BMI, and surgical year) these to 306 primary TKAs performed in patients with a THA or TKA of another joint without a subsequent PJI. Competing risk with death was used for statistical analysis. Multivariate analysis was utilized to evaluate risk factors for PJI in the study cohort. Results. The cumulative incidence of PJI in the study cohort (6.1%) was significantly higher than the matched cohort (2.6%) at 10 years (HR=3.3, p=0.02). Host grade in the study group was not a significant risk factor for PJI. Patients on chronic suppression had a higher rate of PJI (HR=15, p=0.002), with 6 of 7 patients developing a PJI being on chronic suppression. The new infecting microorganism was the same as the previous in only 2 of 7 patients. Conclusion. In this matched cohort study, patients undergoing a clean primary TKA with a history of a TKA or THA PJI in another joint had a 3-fold higher risk of PJI compared to matched controls with a 10-year cumulative incidence of 6.1%. The risk of PJI was 15-fold higher in patients on chronic suppression; further investigation into reasons for this and mitigation strategies is recommended

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

Periprosthetic joint infection (PJI) is a difficult complication requiring a comprehensive eradication protocol. Cure rates have essentially stalled in the last two decades, using methods of antimicrobial cement joint spacers and parenteral antimicrobial agents. Functional spacers with higher-dose antimicrobial-loaded cement and antimicrobial-loaded calcium sulphate beads have emphasized local antimicrobial delivery on the premise that high-dose local antimicrobial delivery will enhance eradication. However, with increasing antimicrobial pressures, microbiota have responded with adaptive mechanisms beyond traditional antimicrobial resistance genes. In this review we describe adaptive resistance mechanisms that are relevant to the treatment of PJI. Some mechanisms are well known, but others are new. The objective of this review is to inform clinicians of the known adaptive resistance mechanisms of microbes relevant to PJI. We also discuss the implications of these adaptive mechanisms in the future treatment of PJI. Cite this article: Bone Joint J 2022;104-B(5):575–580

To reveal if patient reported knee-related pain, function, quality of life, general health and satisfaction at one year after primary total knee arthroplasty (TKA) is different between patients not being subject to revision surgery and those having had early treatment with open debridement and exchange of the tibial insert for postoperative PJI. The Swedish Knee Arthroplasty Register was used to identify 50 patients in the region of Skane that had a primary TKA during the years 2008 – 2012 and within 6 months were revised with open debridement and exchange of the tibial insert due to suspected or verified PJI. Only patients without further revisions were included. Patient reported outcome measurements (PROM) were obtained preoperatively and 1 year postoperatively and included knee related pain, function, quality of life using the Knee injury and Osteoarthritis Outcome Score (KOOS), general health using the EQ-VAS as well as satisfaction with the surgery. The scores were compared to those reported by 3,913 patients having a TKA during the same time but not revised during the first year. Welch's t-test and the Chi2-test were used in statistical analysis. Compared to the controls the infected patients were older (mean age 72 vs 69 years, p = 0.04) and were more morbid (ASA 3; 14/50 patients vs 14%, p = 0.02). The preoperative PROM data were similar. Complete 1 year PROM data was available for 31 of the patients. Those patients reported somewhat worse outcome one year postoperatively than the controls with statistically and clinically significant differences in general health (mean 61 vs 76, p=0.002), KOOS ADL (mean 65 vs 76, p=0.03) and knee related quality of life (mean 51 vs 63, p=0.02) with large variations on individual level. Just over half of the patients (17/29) treated for PJI were very satisfied or satisfied with the surgery compared to 79% of the controls. Patients treated with open debridement and exchange of the tibial insert due to early PJI after primary TKA reported less beneficial postoperative outcome than those without revision surgery during the first postoperative year but with large individual variations

Aims. Periprosthetic hip and knee infection remains one of the most severe complications following arthroplasty, with an incidence between 0.5% to 1%. This study compares the outcomes of revision surgery for periprosthetic joint infection (PJI) following hip and knee arthroplasty prior to and after implementation of a specialist PJI multidisciplinary team (MDT). Methods. Data was retrospectively analyzed from a single centre. In all, 29 consecutive joints prior to the implementation of an infection MDT in November 2016 were compared with 29 consecutive joints subsequent to the MDT conception. All individuals who underwent a debridement antibiotics and implant retention (DAIR) procedure, a one-stage revision, or a two-stage revision for an acute or chronic PJI in this time period were included. The definition of successfully treated PJI was based on the Delphi international multidisciplinary consensus. Results. There were no statistically significant differences in patient demographics or comorbidities between the groups. There was also no significant difference in length of overall hospital stay (p = 0.530). The time taken for formal microbiology advice was significantly shorter in the post MDT group (p = 0.0001). There was a significant difference in failure rates between the two groups (p = 0.001), with 12 individuals (41.38%) pre-MDT requiring further revision surgery compared with one individual (6.67%) post-MDT inception. Conclusion. Our standardized multidisciplinary approach for periprosthetic knee and hip joint infection shows a significant reduction in failure rates following revision surgery. Following implementation of our MDT, our success rate in treating PJI is 96.55%, higher than what current literature suggests. We advocate the role of a specialist infection MDT in the management of patients with a PJI to allow an individualized patient-centred approach and care plan, thereby reducing postoperative complications and failure rates. Cite this article: Bone Jt Open 2021;2(7):509–514

Aims. Synovial fluid white blood cell (WBC) count and percentage of polymorphonuclear cells (%PMN) are elevated at periprosthetic joint infection (PJI). Leucocytes produce different interleukins (IL), including IL-6, so we hypothesized that synovial fluid IL-6 could be a more accurate predictor of PJI than synovial fluid WBC count and %PMN. The main aim of our study was to compare the predictive performance of all three diagnostic tests in the detection of PJI. Methods. Patients undergoing total hip or knee revision surgery were included. In the perioperative assessment phase, synovial fluid WBC count, %PMN, and IL-6 concentration were measured. Patients were labeled as positive or negative according to the predefined cut-off values for IL-6 and WBC count with %PMN. Intraoperative samples for microbiological and histopathological analysis were obtained. PJI was defined as the presence of sinus tract, inflammation in histopathological samples, and growth of the same microorganism in a minimum of two or more samples out of at least four taken. Results. In total, 49 joints in 48 patients (mean age 68 years (SD 10; 26 females (54%), 25 knees (51%)) were included. Of these 11 joints (22%) were infected. The synovial fluid WBC count and %PMN predicted PJI with sensitivity, specificity, accuracy, PPV, and NPV of 82%, 97%, 94%, 90%, and 95%, respectively. Synovial fluid IL-6 predicted PJI with sensitivity, specificity, accuracy, PPV, and NPV of 73%, 95%, 90%, 80%, and 92%, respectively. A comparison of predictive performance indicated a strong agreement between tests. Conclusions. Synovial fluid IL-6 is not superior to synovial fluid WBC count and %PMN in detecting PJI. Level of Evidence: Therapeutic Level II. Cite this article: Bone Jt Open 2020;1-12:737–742

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

Aims. Fungal periprosthetic joint infections (fPJIs) are rare complications, constituting only 1% of all PJIs. Neither a uniform definition for fPJI has been established, nor a standardized treatment regimen. Compared to bacterial PJI, there is little evidence for fPJI in the literature with divergent results. Hence, we implemented a novel treatment algorithm based on three-stage revision arthroplasty, with local and systemic antifungal therapy to optimize treatment for fPJI. Methods. From 2015 to 2018, a total of 18 patients with fPJI were included in a prospective, single-centre study (DKRS-ID 00020409). The diagnosis of PJI is based on the European Bone and Joint Infection Society definition of periprosthetic joint infections. The baseline parameters (age, sex, and BMI) and additional data (previous surgeries, pathogen spectrum, and Charlson Comorbidity Index) were recorded. A therapy protocol with three-stage revision, including a scheduled spacer exchange, was implemented. Systemic antifungal medication was administered throughout the entire treatment period and continued for six months after reimplantation. A minimum follow-up of 24 months was defined. Results. Eradication of infection was achieved in 16 out of 18 patients (88.8%), with a mean follow-up of 35 months (25 to 54). Mixed bacterial and fungal infections were present in seven cases (39%). The interval period, defined as the period of time from explantation to reimplantation, was 119 days (55 to 202). In five patients, a salvage procedure was performed (three cementless modular knee arthrodesis, and two Girdlestone procedures). Conclusion. Therapy for fPJI is complex, with low cure rates according to the literature. No uniform treatment recommendations presently exist for fPJI. Three-stage revision arthroplasty with prolonged systemic antifungal therapy showed promising results. Cite this article: Bone Jt Open 2021;2(8):671–678

Aim

Clear differentiation between aseptic failure and prosthetic joint infection remains one of the goals of modern orthopaedic surgery. New diagnostic methods can provide more precise evaluation of the etiology of prosthetic joint failure. With the introduction of sonication an increasing number of culture-negative prosthetic joint infection were detected. The aim of our study was to evaluate culture-negative prosthetic joint infections in patients who were preoperatively evaluated as aseptic failure.

Aims

Custom-made partial pelvis replacements (PPRs) are increasingly used in the reconstruction of large acetabular defects and have mainly been designed using a triflange approach, requiring extensive soft-tissue dissection. The monoflange design, where primary intramedullary fixation within the ilium combined with a monoflange for rotational stability, was anticipated to overcome this obstacle. The aim of this study was to evaluate the design with regard to functional outcome, complications, and acetabular reconstruction.

Knee arthrodesis is a potential salvage procedure for limb preservation after failure of total knee arthroplasty (TKA) due to infection. In this study, we evaluated the outcome of single-stage knee arthrodesis using an intramedullary cemented coupled nail without bone-on-bone fusion after failed and infected TKA with extensor mechanism deficiency. Between 2002 and 2012, 27 patients (ten female, 17 male; mean age 68.8 years; 52 to 87) were treated with septic single-stage exchange. Mean follow-up duration was 67.1months (24 to 143, n = 27) (minimum follow-up 24 months) and for patients with a minimum follow-up of five years 104.9 (65 to 143,; n = 13). A subjective patient evaluation (Short Form (SF)-36) was obtained, in addition to the Visual Analogue Scale (VAS). The mean VAS score was 1.44 (SD 1.48). At final follow-up, four patients had recurrent infections after arthrodesis (14.8%). Of these, three patients were treated with a one-stage arthrodesis nail exchange; one of the three patients had an aseptic loosening with a third single-stage exchange, and one patient underwent knee amputation for uncontrolled sepsis at 108 months. All patients, including the amputee, indicated that they would choose arthrodesis again. Data indicate that a single-stage knee arthrodesis offers an acceptable salvage procedure after failed and infected TKA.

Cite this article: Bone Joint J 2015;97-B:649–53.

Aims. Despite numerous studies focusing on periprosthetic joint infections (PJIs), there are no robust data on the risk factors and timing of metachronous infections. Metachronous PJIs are PJIs that can arise in the same or other artificial joints after a period of time, in patients who have previously had PJI. Methods. Between January 2010 and December 2018, 661 patients with multiple joint prostheses in situ were treated for PJI at our institution. Of these, 73 patients (11%) developed a metachronous PJI (periprosthetic infection in patients who have previously had PJI in another joint, after a lag period) after a mean time interval of 49.5 months (SD 30.24; 7 to 82.9). To identify patient-related risk factors for a metachronous PJI, the following parameters were analyzed: sex; age; BMI; and pre-existing comorbidity. Metachronous infections were divided into three groups: Group 1, metachronous infections in ipsilateral joints; Group 2, metachronous infections of the contralateral lower limb; and Group 3, metachronous infections of the lower and upper limb. Results. We identified a total of 73 metachronous PJIs: 32 PJIs in Group 1, 38 in Group 2, and one in Group 3. The rate of metachronous infection was 11% (73 out 661 cases) at a mean of four years following first infection. Diabetes mellitus incidence was found significantly more frequently in the metachronous infection group than in non-metachronous infection group. The rate of infection in Group 1 (21.1%) was significantly higher (p = 0.049) compared to Groups 2 (6.2%) and 3 (3%). The time interval of metachronous infection development was shorter in adjacent joint infections. Concordance between the bacterium of the first PJI and that of the metachronous PJI in Group 1 (21/34) was significantly higher than Group 2 (13/38; p = 0.001). Conclusion. The findings of this study suggest that metachronous PJI occurs in more than one in ten patients with an index PJI. Female patients, diabetic patients, and patients with a polymicrobial index PJI are at significantly higher risk for developing a metachronous PJI. Furthermore, metachronous PJIs are significantly more likely to occur in an adjacent joint (e.g. ipsilateral hip and knee) as opposed to a more remote site (i.e. contralateral or upper vs lower limb). Additionally, adjacent joint PJIs occur significantly earlier and are more likely to be caused by the same bacteria as the index PJI. Cite this article: Bone Joint J 2023;105-B(3):294–300

Aims. A higher failure rate has been reported in haematogenous periprosthetic joint infection (PJI) compared to non-haematogenous PJI. The reason for this difference is unknown. We investigated the outcome of haematogenous and non-haematogenous PJI to analyze the risk factors for failure in both groups of patients. Methods. Episodes of knee or hip PJI (defined by the European Bone and Joint Infection Society criteria) treated at our institution between January 2015 and October 2020 were included in a retrospective PJI cohort. Episodes with a follow-up of > one year were stratified by route of infection into haematogenous and non-haematogenous PJI. Probability of failure-free survival was estimated using the Kaplan-Meier method, and compared between groups using log-rank test. Univariate and multivariate analysis was applied to assess risk factors for failure. Results. A total of 305 PJI episodes (174 hips, 131 knees) were allocated to the haematogenous (n = 146) or the non-haematogenous group (n = 159). Among monomicrobial infections, Staphylococcus aureus was the dominant pathogen in haematogenous PJI (76/140, 54%) and coagulase-negative staphylococci in non-haematogenous PJI (57/133, 43%). In both groups, multi-stage exchange (n = 55 (38%) in haematogenous and n = 73 (46%) in non-haematogenous PJI) and prosthesis retention (n = 70 (48%) in haematogenous and n = 48 (30%) in non-haematogenous PJI) were the most common surgical strategies. Median duration of antimicrobial treatment was 13.5 weeks (range, 0.5 to 218 weeks) and similar in both groups. After six years of follow-up, the probability of failure-free survival was significantly lower in haematogenous compared to non-haematogenous PJI (55% vs 74%; p = 0.021). Infection-related mortality was significantly higher in haematogenous than non-haematogenous PJI (7% vs 0% episodes; p = 0.001). Pathogenesis of failure was similar in both groups. Retention of the prosthesis was the only independent risk factor for failure in multivariate analysis in both groups. Conclusion. Treatment failure was significantly higher in haematogenous compared to non-haematogenous PJI. Retention of the prosthesis was the only independent risk factor for failure in both groups. Cite this article: Bone Joint J 2023;105-B(12):1294–1302

Aims. This study aimed to explore the diagnostic value of synovial fluid neutrophil extracellular traps (SF-NETs) in periprosthetic joint infection (PJI) diagnosis, and compare it with that of microbial culture, serum ESR and CRP, synovial white blood cell (WBC) count, and polymorphonuclear neutrophil percentage (PMN%). Methods. In a single health centre, patients with suspected PJI were enrolled from January 2013 to December 2021. The inclusion criteria were: 1) patients who were suspected to have PJI; 2) patients with complete medical records; and 3) patients from whom sufficient synovial fluid was obtained for microbial culture and NET test. Patients who received revision surgeries due to aseptic failure (AF) were selected as controls. Synovial fluid was collected for microbial culture and SF-WBC, SF-PNM%, and SF-NET detection. The receiver operating characteristic curve (ROC) of synovial NET, WBC, PMN%, and area under the curve (AUC) were obtained; the diagnostic efficacies of these diagnostic indexes were calculated and compared. Results. The levels of SF-NETs in the PJI group were significantly higher than those of the AF group. The AUC of SF-NET was 0.971 (95% confidence interval (CI) 0.903 to 0.996), the sensitivity was 93.48% (95% CI 82.10% to 98.63%), the specificity was 96.43% (95% CI 81.65% to 99.91%), the accuracy was 94.60% (95% CI 86.73% to 98.50%), the positive predictive value was 97.73%, and the negative predictive value was 90%. Further analysis showed that SF-NET could improve the diagnosis of culture-negative PJI, patients with PJI who received antibiotic treatment preoperatively, and fungal PJI. Conclusion. SF-NET is a novel and ideal synovial fluid biomarker for PJI diagnosis, which could improve PJI diagnosis greatly. Cite this article: Bone Joint Res 2023;12(2):113–120

Aims. The aim of this study was to estimate the 90-day periprosthetic joint infection (PJI) rates following total knee arthroplasty (TKA) and total hip arthroplasty (THA) for osteoarthritis (OA). Methods. This was a data linkage study using the New South Wales (NSW) Admitted Patient Data Collection (APDC) and the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR), which collect data from all public and private hospitals in NSW, Australia. Patients who underwent a TKA or THA for OA between 1 January 2002 and 31 December 2017 were included. The main outcome measures were 90-day incidence rates of hospital readmission for: revision arthroplasty for PJI as recorded in the AOANJRR; conservative definition of PJI, defined by T84.5, the PJI diagnosis code in the APDC; and extended definition of PJI, defined by the presence of either T84.5, or combinations of diagnosis and procedure code groups derived from recursive binary partitioning in the APDC. Results. The mean 90-day revision rate for infection was 0.1% (0.1% to 0.2%) for TKA and 0.3% (0.1% to 0.5%) for THA. The mean 90-day PJI rates defined by T84.5 were 1.3% (1.1% to 1.7%) for TKA and 1.1% (0.8% to 1.3%) for THA. The mean 90-day PJI rates using the extended definition were 1.9% (1.5% to 2.2%) and 1.5% (1.3% to 1.7%) following TKA and THA, respectively. Conclusion. When reporting the revision arthroplasty for infection, the AOANJRR substantially underestimates the rate of PJI at 90 days. Using combinations of infection codes and PJI-related surgical procedure codes in linked hospital administrative databases could be an alternative way to monitor PJI rates. Cite this article: Bone Joint J 2022;104-B(9):1060–1066

Aims. National joint registries under-report revisions for periprosthetic joint infection (PJI). We aimed to validate PJI reporting to the Australian Orthopaedic Association National Joint Arthroplasty Registry (AOANJRR) and the factors associated with its accuracy. We then applied these data to refine estimates of the total national burden of PJI. Methods. A total of 561 Australian cases of confirmed PJI were captured by a large, prospective observational study, and matched to data available for the same patients through the AOANJRR. Results. In all, 501 (89.3%) cases of PJI recruited to the prospective observational study were successfully matched with the AOANJRR database. Of these, 376 (75.0%) were captured by the registry, while 125 (25.0%) did not have a revision or reoperation for PJI recorded. In a multivariate logistic regression analysis, early (within 30 days of implantation) PJIs were less likely to be reported (adjusted odds ratio (OR) 0.56; 95% confidence interval (CI) 0.34 to 0.93; p = 0.020), while two-stage revision procedures were more likely to be reported as a PJI to the registry (OR 5.3 (95% CI 2.37 to 14.0); p ≤ 0.001) than debridement and implant retention or other surgical procedures. Based on this data, the true estimate of the incidence of PJI in Australia is up to 3,900 cases per year. Conclusion. In Australia, infection was not recorded as the indication for revision or reoperation in one-quarter of those with confirmed PJI. This is better than in other registries, but suggests that registry-captured estimates of the total national burden of PJI are underestimated by at least one-third. Inconsistent PJI reporting is multifactorial but could be improved by developing a nested PJI registry embedded within the national arthroplasty registry. Cite this article: Bone Jt Open 2022;3(5):367–373

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. Methods. We reviewed our institutional joint arthroplasty database and identified 41 patients diagnosed with fungal PJIs and treated with two-stage exchange arthroplasty after primary total knee arthroplasty (TKA) between January 2001 and December 2020, and compared them with those who had non-fungal PJIs during the same period. After propensity score matching based on age, sex, BMI, American Society of Anesthesiologists grade, and Charlson Comorbidity Index, 40 patients in each group were successfully matched. The surgical and antimicrobial treatment, patient demographic and clinical characteristics, recurrent infections, survival rates, and relevant risk factors that affected joint survivorship were analyzed. We defined treatment success as a well-functioning arthroplasty without any signs of a PJI, and without antimicrobial suppression, at a minimum follow-up of two years from the time of reimplantation. Results. The fungal PJI group demonstrated a significantly worse treatment success rate at the final follow-up than the non-fungal PJI group (65.0% (26/40) vs 85.0% (34/40); p < 0.001). The mean prosthesis-free interval was longer in the fungal PJI group than in the non-fungal PJI group (6.7 weeks (SD 5.8) vs 4.1 weeks (SD 2.5); p = 0.020). The rate of survivorship free from reinfection was worse in the fungal PJI group (83.4% (95% confidence interval (CI) 64.1 to 92.9) at one year and 76.4% (95% CI 52.4 to 89.4) at two years) than in the non-fungal PJI group (97.4% (95% CI 82.7 to 99.6) at one year and 90.3% (95% CI 72.2 to 96.9) at two years), but the differences were not significant (p = 0.270). Cox proportional hazard regression analysis identified the duration of the prosthesis-free interval as a potential risk factor for failure (hazard ratio 1.128 (95% CI 1.003 to 1.268); p = 0.043). Conclusion. Fungal PJIs had a lower treatment success rate than non-fungal PJIs despite two-stage revision arthroplasty and appropriate antifungal treatment. Our findings highlight the need for further developments in treating fungal PJIs. Cite this article: Bone Joint J 2023;105-B(12):1286–1293

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. Methods. A total of 1,171 total hip arthroplasty (THA) patients with MoM articulations from August 2000 to March 2014 were retrospectively identified. Of those, 328 patients underwent metal artefact reduction sequence MRI and had minimum two years’ clinical follow-up, and met our inclusion criteria. Data collected included demographic details, surgical indication, laterality, implants used, history of pseudotumour, and their corresponding preoperative ESR (mm/hr) and CRP (mg/dl) levels. Multivariate logistic regression modelling was used to evaluate PJI and history of pseudotumour, and receiver operating characteristic curves were created to assess the diagnostic capabilities of ESR and CRP to determine the presence of infection in patients undergoing revision surgery. Results. The rate of PJI for all identified MoM THAs was 3.5% (41/1,171), with a mean follow-up of 10.9 years (2.0 to 20.4). Of the patients included in the final cohort, 8.2% (27/328) had PJI, with a mean follow-up of 12.2 years (2.3 to 20.4). Among this cohort, 31.1% (102/328) had a history of pseudotumour. The rate of PJI in these patients was 14.7% (15/102), which was greater than those without pseudotumour, 5.3% (12/226) (p = 0.008). Additionally, logistic regression analysis showed an association between history of pseudotumour and PJI (odds ratio 4.36 (95% confidence interval 1.77 to 11.3); p = 0.002). Optimal diagnostic cutoffs for PJI in patients with history of pseudotumour versus those without were 33.1 mm/hr and 24.5 mm/hr for ESR and 7.37 mg/dl and 1.88 mg/dl for CRP, respectively. Conclusion. Patients with history of pseudotumour secondary to MoM THA had a higher likelihood of infection than those without. While suspicion of infection should be high for these patients, ESR and CRP cutoffs published by the European Bone and Joint Infection Society may not be appropriate for patients with a history of pseudotumour, as ESR and CRP levels suggestive of PJI are likely to be higher than for those without a pseudotumour. Additional investigation, such as aspiration, is highly recommended for these patients unless clinical suspicion and laboratory markers are low. Cite this article: Bone Joint J 2024;106-B(6):555–564

Aims. This study aimed to explore the role of small colony variants (SCVs) of Staphylococcus aureus in intraosseous invasion and colonization in patients with periprosthetic joint infection (PJI). Methods. A PJI diagnosis was made according to the MusculoSkeletal Infection Society (MSIS) for PJI. Bone and tissue samples were collected intraoperatively and the intracellular invasion and intraosseous colonization were detected. Transcriptomics of PJI samples were analyzed and verified by polymerase chain reaction (PCR). Results. SCVs can be isolated from samples collected from chronic PJIs intraoperatively. Transmission electron microscopy (TEM) and immunofluorescence (IF) showed that there was more S. aureus in bone samples collected from chronic PJIs, but much less in bone samples from acute PJIs, providing a potential mechanism of PJI. Immunofluorescence results showed that SCVs of S. aureus were more likely to invade osteoblasts in vitro. Furthermore, TEM and IF also demonstrated that SCVs of S. aureus were more likely to invade and colonize in vivo. Cluster analysis and principal component analysis (PCA) showed that there were substantial differences in gene expression profiles between chronic and acute PJI. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these differentially expressed genes were enriched to chemokine-related signal pathways. PCR also verified these results. Conclusion. Our study has shown that the S. aureus SCVs have a greater ability to invade and colonize in bone, resulting in S. aureus remaining in bone tissues long-term, thus explaining the pathogenesis of chronic PJI. Cite this article: Bone Joint Res 2022;11(12):843–853

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. The aims of this study were to determine the incidence and factors for developing periprosthetic joint infection (PJI) following hemiarthroplasty (HA) for hip fracture, and to evaluate treatment outcome and identify factors associated with treatment outcome. Methods. A retrospective review was performed of consecutive patients treated for HA PJI at a tertiary referral centre with a mean 4.5 years’ follow-up (1.6 weeks to 12.9 years). Surgeries performed included debridement, antibiotics, and implant retention (DAIR) and single-stage revision. The effect of different factors on developing infection and treatment outcome was determined. Results. A total of 1,984 HAs were performed during the study period, and 44 sustained a PJI (2.2%). Multiple logistic regression analysis revealed that a higher CCI score (odds ratio (OR) 1.56 (95% confidence interval (CI) 1.117 to 2.187); p = 0.003), peripheral vascular disease (OR 11.34 (95% CI 1.897 to 67.810); p = 0.008), cerebrovascular disease (OR 65.32 (95% CI 22.783 to 187.278); p < 0.001), diabetes (OR 4.82 (95% CI 1.903 to 12.218); p < 0.001), moderate-to-severe renal disease (OR 5.84 (95% CI 1.116 to 30.589); p = 0.037), cancer without metastasis (OR 6.42 (95% CI 1.643 to 25.006); p = 0.007), and metastatic solid tumour (OR 15.64 (95% CI 1.499 to 163.087); p = 0.022) were associated with increasing PJI risk. Upon final follow-up, 17 patients (38.6%) failed initial treatment and required further surgery for HA PJI. One-year mortality was 22.7%. Factors associated with treatment outcome included lower preoperative Hgb level (97.9 g/l (SD 11.4) vs 107.0 g/l (SD 16.1); p = 0.009), elevated CRP level (99.1 mg/l (SD 63.4) vs 56.6 mg/l (SD 47.1); p = 0.030), and type of surgery. There was lower chance of success with DAIR (42.3%) compared to revision HA (66.7%) or revision with conversion to total hip arthroplasty (100%). Early-onset PJI (≤ six weeks) was associated with a higher likelihood of treatment failure (OR 3.5 (95% CI 1.2 to 10.6); p = 0.007) along with patients treated by a non-arthroplasty surgeon (OR 2.5 (95% CI 1.2 to 5.3); p = 0.014). Conclusion. HA PJI initially treated with DAIR is associated with poor chances of success and its value is limited. We strongly recommend consideration of a single-stage revision arthroplasty with cemented components. Cite this article: Bone Jt Open 2022;3(12):924–932

Aims. The management of periprosthetic joint infection (PJI) remains a major challenge in orthopaedic surgery. In this study, we aimed to characterize the local bone microstructure and metabolism in a clinical cohort of patients with chronic PJI. Methods. Periprosthetic femoral trabecular bone specimens were obtained from patients suffering from chronic PJI of the hip and knee (n = 20). Microbiological analysis was performed on preoperative joint aspirates and tissue specimens obtained during revision surgery. Microstructural and cellular bone parameters were analyzed in bone specimens by histomorphometry on undecalcified sections complemented by tartrate-resistant acid phosphatase immunohistochemistry. Data were compared with control specimens obtained during primary arthroplasty (n = 20) and aseptic revision (n = 20). Results. PJI specimens exhibited a higher bone volume, thickened trabeculae, and increased osteoid parameters compared to both control groups, suggesting an accelerated bone turnover with sclerotic microstructure. On the cellular level, osteoblast and osteoclast parameters were markedly increased in the PJI cohort. Furthermore, a positive association between serum (CRP) but not synovial (white blood cell (WBC) count) inflammatory markers and osteoclast indices could be detected. Comparison between different pathogens revealed increased osteoclastic bone resorption parameters without a concomitant increase in osteoblasts in bone specimens from patients with Staphylococcus aureus infection, compared to those with detection of Staphylococcus epidermidis and Cutibacterium spp. Conclusion. This study provides insights into the local bone metabolism in chronic PJI, demonstrating osteosclerosis with high bone turnover. The fact that Staphylococcus aureus was associated with distinctly increased osteoclast indices strongly suggests early surgical treatment to prevent periprosthetic bone alterations. Cite this article: Bone Joint Res 2023;12(10):644–653

Aims. Current diagnostic tools are not always able to effectively identify periprosthetic joint infections (PJIs). Recent studies suggest that circulating microRNAs (miRNAs) undergo changes under pathological conditions such as infection. The aim of this study was to analyze miRNA expression in hip arthroplasty PJI patients. Methods. This was a prospective pilot study, including 24 patients divided into three groups, with eight patients each undergoing revision of their hip arthroplasty due to aseptic reasons, and low- and high-grade PJI, respectively. The number of intraoperative samples and the incidence of positive cultures were recorded for each patient. Additionally, venous blood samples and periarticular tissue samples were collected from each patient to determine miRNA expressions between the groups. MiRNA screening was performed by small RNA-sequencing using the miRNA next generation sequencing (NGS) discovery (miND) pipeline. Results. Overall, several miRNAs in plasma and tissue were identified to be progressively deregulated according to ongoing PJI. When comparing the plasma samples, patients with a high-grade infection showed significantly higher expression levels for hsa-miR-21-3p, hsa-miR-1290, and hsa-miR-4488, and lower expression levels for hsa-miR-130a-3p and hsa-miR-451a compared to the aseptic group. Furthermore, the high-grade group showed a significantly higher regulated expression level of hsa-miR-1260a and lower expression levels for hsa-miR-26a-5p, hsa-miR-26b-5p, hsa-miR-148b-5p, hsa-miR-301a-3p, hsa-miR-451a, and hsa-miR-454-3p compared to the low-grade group. No significant differences were found between the low-grade and aseptic groups. When comparing the tissue samples, the high-grade group showed significantly higher expression levels for 23 different miRNAs and lower expression levels for hsa-miR-2110 and hsa-miR-3200-3p compared to the aseptic group. No significant differences were found in miRNA expression between the high- and low-grade groups, as well as between the low-grade and aseptic groups. Conclusion. With this prospective pilot study, we were able to identify a circulating miRNA signature correlating with high-grade PJI compared to aseptic patients undergoing hip arthroplasty revision. Our data contribute to establishing miRNA signatures as potential novel diagnostic and prognostic biomarkers for PJI. Cite this article: Bone Jt Open 2024;5(6):479–488

Aims. The diagnosis of periprosthetic joint infection (PJI) can be challenging as the symptoms are similar to other conditions, and the markers used for diagnosis have limited sensitivity and specificity. Recent research has suggested using blood cell ratios, such as platelet-to-volume ratio (PVR) and platelet-to-lymphocyte ratio (PLR), to improve diagnostic accuracy. The aim of the study was to further validate the effectiveness of PVR and PLR in diagnosing PJI. Methods. A retrospective review was conducted to assess the accuracy of different marker combinations for diagnosing chronic PJI. A total of 573 patients were included in the study, of which 124 knees and 122 hips had a diagnosis of chronic PJI. Complete blood count and synovial fluid analysis were collected. Recently published blood cell ratio cut-off points were applied to receiver operating characteristic curves for all markers and combinations. The area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values were calculated. Results. The results of the analysis showed that the combination of ESR, CRP, synovial white blood cell count (Syn. WBC), and polymorphonuclear neutrophil percentage (PMN%) with PVR had the highest AUC of 0.99 for knees, with sensitivity of 97.73% and specificity of 100%. Similarly, for hips, this combination had an AUC of 0.98, sensitivity of 96.15%, and specificity of 100.00%. Conclusion. This study supports the use of PVR calculated from readily available complete blood counts, combined with established markers, to improve the accuracy in diagnosing chronic PJI in both total hip and knee arthroplasties. Cite this article: Bone Jt Open 2023;4(11):881–888

Aims. Periprosthetic joint infection (PJI) demonstrates the most feared complication after total joint replacement (TJR). The current work analyzes the demographic, comorbidity, and complication profiles of all patients who had in-hospital treatment due to PJI. Furthermore, it aims to evaluate the in-hospital mortality of patients with PJI and analyze possible risk factors in terms of secondary diagnosis, diagnostic procedures, and complications. Methods. In a retrospective, cross-sectional study design, we gathered all patients with PJI (International Classification of Diseases (ICD)-10 code: T84.5) and resulting in-hospital treatment in Germany between 1 January 2019 and 31 December 2022. Data were provided by the Institute for the Hospital Remuneration System in Germany. Demographic data, in-hospital deaths, need for intensive care therapy, secondary diagnosis, complications, and use of diagnostic instruments were assessed. Odds ratios (ORs) with 95% confidence intervals (CIs) for in-hospital mortality were calculated. Results. A total of 52,286 patients were included, of whom 1,804 (3.5%) died. Hypertension, diabetes mellitus, and obesity, the most frequent comorbidities, were not associated with higher in-hospital mortality. Cardiac diseases as atrial fibrillation, cardiac pacemaker, or three-vessel coronary heart disease showed the highest risk for in-hospital mortality. Postoperative anaemia occurred in two-thirds of patients and showed an increased in-hospital mortality (OR 1.72; p < 0.001). Severe complications, such as organ failure, systemic inflammatory response syndrome (SIRS), or septic shock syndrome showed by far the highest association with in-hospital mortality (OR 39.20; 95% CI 33.07 to 46.46; p < 0.001). Conclusion. These findings highlight the menace coming from PJI. It can culminate in multi-organ failure, SIRS, or septic shock syndrome, along with very high rates of in-hospital mortality, thereby highlighting the vulnerability of these patients. Particular attention should be paid to patients with cardiac comorbidities such as atrial fibrillation or three-vessel coronary heart disease. Risk factors should be optimized preoperatively, anticoagulant therapy stopped and restarted on time, and sufficient patient blood management should be emphasized. Cite this article: Bone Jt Open 2024;5(4):367–373

Aims. The duration of systemic antibiotic treatment following first-stage revision surgery for periprosthetic joint infection (PJI) after total hip arthroplasty (THA) is contentious. Our philosophy is to perform an aggressive debridement, and to use a high local concentration of targeted antibiotics in cement beads and systemic prophylactic antibiotics alone. The aim of this study was to assess the success of this philosophy in the management of PJI of the hip using our two-stage protocol. Methods. The study involved a retrospective review of our prospectively collected database from which we identified all patients who underwent an intended two-stage revision for PJI of the hip. All patients had a diagnosis of PJI according to the major criteria of the Musculoskeletal Infection Society (MSIS) 2013, a minimum five-year follow-up, and were assessed using the MSIS working group outcome-reporting tool. The outcomes were grouped into ‘successful’ or ‘unsuccessful’. Results. A total of 299 two-stage revision THAs in 289 patients met the inclusion criteria, of whom 258 (86%) proceeded to second-stage surgery. Their mean age was 68.1 years (28 to 92). The median follow-up was 10.7 years (interquartile range (IQR) 6.3 to 15.0). A 91% success rate was seen in those patients who underwent reimplantation, decreasing to 86% when including those who did not proceed to reimplantation. The median duration of postoperative systemic antibiotics following the first stage was five days (IQR 5 to 9). There was no significant difference in outcome between those patients who were treated with antibiotics for ≤ 48 hours (p = 0.961) or ≤ five days (p = 0.376) compared with those who were treated with longer courses. Greater success rates were seen for Gram-positive PJIs (87%) than for Gram-negative (84%) and mixed-Gram PJIs (72%; p = 0.098). Conclusion. Aggressive surgical debridement with a high local concentration of targeted antibiotics at the time of first-stage revision surgery for PJI of the hip, without prolonged systemic antibiotics, provides a high rate of success, responsible antibiotic stewardship, and reduced hospital costs. Cite this article: Bone Joint J 2023;105-B(5):511–517

Aims. Despite recent literature questioning their use, vancomycin and clindamycin often substitute cefazolin as the preoperative antibiotic prophylaxis in primary total knee arthroplasty (TKA), especially in the setting of documented allergy to penicillin. Topical povidone-iodine lavage and vancomycin powder (VIP) are adjuncts that may further broaden antimicrobial coverage, and have shown some promise in recent investigations. The purpose of this study, therefore, is to compare the risk of acute periprosthetic joint infection (PJI) in primary TKA patients who received cefazolin and VIP to those who received a non-cephalosporin alternative and VIP. Methods. This was a retrospective cohort study of 11,550 primary TKAs performed at an orthopaedic hospital between 2013 and 2019. The primary outcome was PJI occurring within 90 days of surgery. Patients were stratified into two groups (cefazolin vs non-cephalosporin) based on their preoperative antibiotic. All patients also received the VIP protocol at wound closure. Bivariate and multiple logistic regression analyses were performed to control for potential confounders and identify the odds ratio of PJI. Results. In all, 10,484 knees (90.8%) received cefazolin, while 1,066 knees (9.2%) received a non-cephalosporin agent (either vancomycin or clindamycin) as preoperative prophylaxis. The rate of PJI in the cefazolin group (0.5%; 48/10,484) was significantly lower than the rate of PJI in the non-cephalosporin group (1.0%; 11/1,066) (p = 0.012). After controlling for confounding variables, the odds ratio (OR) of developing a PJI was increased in the non-cephalosporin cohort compared to the cefazolin cohort (OR 2.389; 1.2 to 4.6); p = 0.01). Conclusion. Despite the use of topical irrigant solutions and addition of local antimicrobial agents, the use of a non-cephalosporin perioperative antibiotic continues to be associated with a greater risk of TKA PJI compared to cefazolin. Strategies that increase the proportion of patients receiving cefazolin rather than non-cephalosporin alternatives must be emphasized. Cite this article: Bone Jt Open 2022;3(1):35–41

Aims. The aim of this meta-analysis is to assess the association between exchange of modular parts in debridement, antibiotics, and implant retention (DAIR) procedure and outcomes for hip and knee periprosthetic joint infection (PJI). Methods. We conducted a systematic search on PubMed, Embase, Web of Science, and Cochrane library from inception until May 2021. Random effects meta-analyses and meta-regression was used to estimate, on a study level, the success rate of DAIR related to component exchange. Risk of bias was appraised using the (AQUILA) checklist. Results. We included 65 studies comprising 6,630 patients. The pooled overall success after DAIR for PJI was 67% (95% confidence interval (CI) 63% to 70%). This was 70% (95% CI 65% to 75%) for DAIR for hip PJI and 63% (95% CI 58% to 69%) for knee PJI. In studies before 2004 (n = 27), our meta-regression analysis showed a 3.5% increase in success rates for each 10% increase in component exchange in DAIR for hip PJI and a 3.1% increase for each 10% increase in component exchange for knee PJI. When restricted to studies after 2004 (n = 37), this association changed: for DAIR for hip PJI a decrease in successful outcome by 0.5% for each 10% increase in component exchange and for DAIR for knee PJI this was a 0.01% increase in successful outcome for each 10% increase in component exchange. Conclusion. This systematic review and meta-regression found no benefit of modular component exchange on reduction of PJI failure. This limited effect should be weighed against the risks for the patient and cost on a case-by-case basis. The association between exchange of modular components and outcome changed before and after 2004. This suggests the effect seen after 2004 may reflect a more rigorous, evidence-based, approach to the infected implant compared to the years before. Level of Evidence: Level III. Cite this article: Bone Jt Open 2021;2(10):806–812

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