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

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

Aim. Periprosthetic joint infection (PJI) is a complication of total joint arthroplasty that typically requires revision surgery for treatment. Systemic antibiotics are usually held prior to surgery to improve yield of intraoperative cultures. However, recent studies suggest that preoperative aspirations have a high concordance with intraoperative cultures, which may allow surgeons to initiate antibiotic treatment earlier. The purpose of the study was to investigate the effect of Pre-surgical systemic antibiotic therapy on the bacterial burden within the periprosthetic space and systemic immune reaction. Method. PJI was induced with MSSA (Xen36) S. aureus in the right knee of 16-week old, female, C57BL6 mice using a previously validated murine model. Mice were randomized to three groups (n=8, each): control; Vanc, receiving systemic vancomycin (110mg/kg, SQ, twice daily); or VancRif receiving vancomycin same as in Vanc group, plus rifampin (12mg/kg dose, IV, once daily). Following 2 weeks of treatment, mice were euthanized and periprosthetic bone, soft tissue and the implant were harvested. Bacterial burden, colony forming units (CFUs), was quantified in soft tissue, tibial bone, and on the implant. Specifically, tissues were homogenized and serially plated for CFUs, while the implant was sonicated and then plated for CFUs. The host immune response was analysed through weighing inguinal and iliac lymph nodes and through measuring serum amyloid A (SAA). Non-parametric pairwise group comparisons of the three outcome measures were performed using a Mann-Whitney U test. Results. VancRif, the combined treatment significantly reduced bacterial burden in the periprosthetic soft tissue, bone, and implant compared to control (p<0.001) and Vanc alone (p<0.001). While not significant, Vanc alone did reduce bacterial load as compared to control. The ipsilateral weight of the iliac lymph nodes was significantly reduced in Vanc and VancRif mice compared to controls (p<0.001), was well as in VancRif versus Vanc alone (p<0.001). Interestingly, SAA levels did not significantly differ among all groups. During tissue harvesting, minimal purulence was observed in antibiotic treatment groups, unlike controls. Conclusions. Treating active PJI with vancomycin alone decreases periprosthetic bacterial loads and reduces the local immunological response. This effect is significantly enhanced with the combined rifampin use. These findings could suggest that when culture positive PJI is diagnosed, pre-surgical treatment with antibiotics may decrease immunosuppression and soft tissue infiltration, leading to a better chance of infection cure with subsequent surgical debridement. Histological investigations and repeat experiments involving subsequent surgical treatment are underway. Acknowledgements. Funding comes from internal institutional grants

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

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

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

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

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

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

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

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