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With a significant rise in the number of arthroplasty procedures performed worldwide, the increasing revision burden posed by periprosthetic joint infection (PJI) is a matter of growing concern. In spite of various attempts to diagnose PJI, there are no defined tests that can be called a gold standard. Given the importance of early diagnosis in PJI, newer tests and biomarkers have been introduced to improve cumulative diagnostic accuracy. Novel biomarkers like calprotectin, lipocalcin, monocyte-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and platelet-to-mean platelet volume ratio have demonstrated a potential as diagnostic biomarkers for PJI. This article discusses the relevance of available and newly described diagnostic biomarkers to provide a perspective on the practical applicability in current medical practice, as well as highlights some recent advances in biomarkers for the diagnosis of PJI. [ABSTRACT FROM AUTHOR]

Background: In severe cases of periprosthetic joint infection involving negative host-dependent factors, individual-based decisions between a curative therapy vs. salvage procedure are necessary. We aimed to review salvage procedures in severe periprosthetic joint infection cases, where a gold standard of a curative two-stage exchange can no longer be achieved. The options of knee arthrodesis, amputation, persistent fistula (stable drainage), or a debridement, antibiotics, and implant retention procedure in late-onset cases are discussed, including lifelong antibiotic suppression alone. Methods: We focused on known salvage procedures for severe periprosthetic joint infection of the hip and knee, such as amputation, arthrodesis, antibiotic suppression, persistent fistula, and debridement, antibiotics, and implant retention in late-stage infections, and the role of local antibiotics. The current literature regarding indications and outcomes was reviewed. Results: Whereas a successful single-stage above-knee amputation can be a curative effort in younger patients, this is associated with limited outcome in older patients, as the proportion who receive an exoprosthesis leading to independent mobility is low. Therefore, arthrodesis using an intramedullary modular nail is an option for limb salvage, pain reduction, and preservation of quality of life and everyday life mobility, when revision total knee arthroplasty is not an option. Carrying out a persistent fistula using a stable drainage system, as well as a lifelong antibiotic suppression therapy, can be an option, in cases where no other surgery is possible. Active clinical surveillance should then be carried out. A debridement, antibiotics, and implant retention procedure in combination with local degradable antibiotics can be used and is an encouraging new option, but should not been carried out twice. Conclusion: Whereas the gold standard in periprosthetic joint infection treatment of late infections remains the exchange of the prosthesis, salvage procedures should be considered in the cases of reduced life expectancy, several recurrences of the infection, patients having preference and negative host factors. In these cases, the appropriate salvage procedure can temporarily lead to remission of the infection and the possibility to maintain mobility. [ABSTRACT FROM AUTHOR]

Background: It is traditionally believed that presence of fungal infection in the nail or skin of patients is a risk factor for subsequent infection. The literature is devoid of any evidence to confirm or refute this belief. This study examined a possible relationship between the presence of superficial skin or nail mycoses and subsequent periprosthetic joint infection (PJI) in patients undergoing total joint arthroplasty (TJA). Methods: This is a single-centre, retrospective study of patients who underwent primary TJA between 2000 and 2018. 55 patients with superficial mycoses of skin or nail, at the time of arthroplasty were identified and a variable number matching with up to a 1:5 ratio was performed with 182 patients undergoing TJA who had no superficial mycosis. The groups were further divided into knee and hip TJA. The outcome of TJA in the cohorts was compared. Results: Preoperative demographics were similar between the 2 groups. The incidence of PJI in patients undergoing TKA within a year was significantly higher in patients with superficial mycosis at 8.6% (3/35) compared to 0% (0/120) in patients without mycosis. However, all infections were caused by bacterial species and none were fungal. Multiple regression analysis demonstrated that the presence of superficial mycosis had a strong correlation with development of PJI postoperatively in our TKA cohort. Conclusions: Identification of fungal infection (mycosis) of skin and nail in patients awaiting TJA is important. These patients appear to have a higher risk for developing bacterial PJI than those without fungal infections. Further study is needed to determine if treatment of these patients prior to arthroplasty stands to reverse the high risk for PJI that these patients carry. [ABSTRACT FROM AUTHOR]

The isolation of an infective pathogen can be challenging in some patients with active, clinically apparent infectious diseases. Despite efforts in the microbiology lab to improve the sensitivity of culture in orthopedic implant-associated infections, the clinically relevant information often falls short of expectations. The management of peri-prosthetic joint infections (PJI) provides an excellent example of the use and benefits of newer diagnostic technologies to supplement the often-inadequate yield of traditional culture methods as a substantial percentage of orthopedic infections are culture-negative. Next-generation sequencing (NGS) has the potential to improve upon this yield. Bringing molecular diagnostics into practice can provide critical information about the nature of the infective organisms and allow targeted therapy in these otherwise challenging situations. This review article describes the current state of knowledge related to the use and potential of NGS to diagnose infections, particularly in the setting of PJIs. [ABSTRACT FROM AUTHOR]

Identification of the causative organism(s) in periprosthetic joint infection (PJI) is a challenging task. The shortcomings of traditional cultures have been emphasized in recent literature, culminating in a clinical entity known as "culture-negative PJI." Amidst the growing burden of biofilm infections that are inherently difficult to culture, the field of clinical microbiology has seen a paradigm shift from culture-based to molecular-based methods. These novel techniques hold much promise in the demystification of culture-negative PJI and revolutionization of the microbiology laboratory. This article outlines the clinical implications of culture-negative PJI, common causes of this diagnostic conundrum, established strategies to improve culture yield, and newer molecular techniques to detect infectious organisms. [ABSTRACT FROM AUTHOR]

Introduction: The objectives of this study are to report the rates of positive intraoperative cultures obtained during conversion total hip arthroplasty (THA) according to index surgery, and to describe the natural history of treatment for a consecutive series of patients with unexpected positive intraoperative cultures during conversion THA. Methods: We reviewed all patients at 2 institutions undergoing conversion THA from prior open reduction and internal fixation (ORIF) of acetabular and hip fractures or hemiarthroplasty for displaced femoral neck fractures from 2011 to 2018. Intraoperative cultures were taken in 105 patients. Positive intraoperative cultures during conversion were recorded and managed with an infectious diseases consult. The outcomes including PJI at 90 days and 1 year follow-up were documented. Results: Overall, 19 of 105 patients (18%) undergoing conversion THA had positive intraoperative cultures, with the highest rates in the hemiarthroplasty 7/16 (44%) and acetabular ORIF 9/48 (19%) groups. All 19 patients were initially treated conservatively: 8 received IV antibiotics, 10 received no additional therapy, and 1 received oral antibiotics. 4/9 acetabular fracture conversions developed PJI at 1 year, with 3 requiring multiple irrigation and debridement/polyethylene exchanges to control the infection while the 4th patient required 2-stage exchange. There were no 1-year PJI from any of the other index procedures after conversion. All 7 hemiarthroplasty patients with positive cultures were treated to resolution with 4–8 weeks IV antibiotics alone. Conclusions: Patients undergoing conversion THA from prior hip or acetabular fracture have a high rate of positive intraoperative cultures. As such, all patients undergoing conversion THA from prior hip or acetabular fracture fixation should undergo thorough diagnostic workup prior to surgery, and have intraoperative cultures obtained during surgery if infection remains suspicious. Further work should be performed to develop MSIS criteria for preoperative management of patients undergoing conversion THA. [ABSTRACT FROM AUTHOR]

Background Rifampin is generally advised in the treatment of acute staphylococcal periprosthetic joint infections (PJI). However, if, when, and how to use rifampin remains a matter of debate. We evaluated the outcome of patients treated with and without rifampin, and analyzed the influence of timing, dose and co-antibiotic. Methods Acute staphylococcal PJIs treated with surgical debridement between 1999 and 2017, and a minimal follow-up of 1 year were evaluated. Treatment failure was defined as the need for any further surgical procedure related to infection, PJI-related death or the need for suppressive antimicrobial treatment. Results A total of 669 patients were analyzed. Treatment failure was 32.2% (131/407) in patients treated with rifampin and 54.2% (142/262) in whom rifampin was withheld (P <.001). The most prominent effect of rifampin was observed in knees (treatment failure 28.6% versus 63.9%, respectively, P <.001). The use of rifampin was an independent predictor of treatment success in the multi-variate analysis (OR 0.30, 95% CI 0.20 – 0.45). In the rifampin group, the use of a co-antibiotic other than a fluoroquinolone or clindamycin (OR 10.1, 95% CI 5.65 – 18.2) and the start of rifampin within 5 days after surgical debridement (OR 1.96, 95% CI 1.08 – 3.65) were predictors of treatment failure. The dosing of rifampin had no effect on outcome. Conclusions Our data supports the use of rifampin in acute staphylococcal PJIs treated with surgical debridement, particularly in knees. Immediate start of rifampin after surgical debridement should probably be discouraged, but requires further investigation. [ABSTRACT FROM AUTHOR]

Abstract: Orthopaedic device-related infection is one of the most devastating complications in orthopaedic and trauma surgery. With increasing life expectancies as well as the lifelong risk of bacterial seeding on an implant, the prevention and treatment of device-related infection remains an important area for research and development. To facilitate information exchange and enhance collaboration among various stakeholders in the orthopaedic community, the U.S. Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) organized an inaugural workshop on orthopaedic device-related infections, exploring the regulatory challenges that are faced when proceeding from the bench level to marketing and clinical implementation of new infection-control devices and products. This article summarizes the perspectives of scientists, clinicians, and industry partners on the current regulatory approval process for orthopaedic anti-infective technologies as well as the proposed strategies to overcome these regulatory challenges. [ABSTRACT FROM AUTHOR]

Background: The current preferred treatment for chronic hip and knee periprosthetic joint infection (PJI) involves both surgical intervention and antibiotic treatment as part of a two-stage revision. The purpose of this study is to determine how often patients who underwent a two-stage revision for chronic PJI developed a subsequent antibiotic-resistant infection.Methods: We retrospectively reviewed the clinical records of 142 patients who underwent a two-stage revision for a chronic culture-positive PJI from January 2014 to May 2019. Demographic data and risk factors for PJI were identified. Resistance was defined in accordance with microbiology laboratory report and minimum inhibitory concentration. Statistical analysis consisted of descriptive statistics and univariate analysis.Results: Only 10 of the 142 patients (7.04%) demonstrated emergence of resistance to antibiotics across their two-stage revision. At reimplantation, 25 (17.6%) patients had positive cultures. Of these, 16 patients presented with a novel organism and 9 patients had positive culture for the same organism as the initial infection. During the entire course of the two-stage revision, including spacer exchanges and irrigation and debridement procedures, 15 (10.56%) patients demonstrated persistent infections, whereas 25 (17.6%) patients presented with novel infections. 26 (18.3%) patients had reinfection of the same joint within one year.Conclusion: In the given cohort, there does not appear to be a major emergence of antibiotic resistant organisms in patients undergoing two-stage exchange arthroplasty and antibiotic treatment. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of periprosthetic shoulder infection continues to be difficult to make with confidence. Serum D-dimer has proven to be effective as a screening tool for periprosthetic joint infection in other major joints; however, it has yet to be evaluated for use in periprosthetic shoulder infection.Questions/purposes: (1) Is D-dimer elevated in patients with probable or definite periprosthetic shoulder infections? (2) What is the diagnostic accuracy of D-dimer for periprosthetic shoulder infections? (3) What are the diagnostic accuracies of serum tests (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], and D-dimer), singly and in combination?Methods: Between March 2016 and March 2020, 94 patients undergoing revision total shoulder arthroplasty (anatomic or reverse) at a single institution had preoperative serum testing with CRP, ESR, and D-dimer. These 94 patients were a subset of 189 revision shoulder arthroplasties performed at this institution during the study period who met inclusion criteria and consented to participate. Included patients had a mean ± SD age of 69 ± 8 years, and 56% (53 of 94) were men. Patient records were reviewed to classify patients as definitely having infection, probably having infection, possibly having infection, or unlikely to have an infection, according to the International Consensus Meeting (ICM) definition of periprosthetic shoulder infection. Statistical analyses, including a receiver operating characteristic curve analysis, were performed to quantify the diagnostic value of D-dimer for periprosthetic shoulder infection. Based on the ICM definition, 4% (4 of 94), 15% (14 of 94), 14% (13 of 94), and 67% (63 of 94) of patients had definite, probable, possible, or unlikely periprosthetic shoulder infections.Results: D-dimer was elevated in patients with definite or probable infections (median [range] 661 ng/mL [150 to 8205]) compared with those with possible infections or those who were unlikely to have an infection (263 ng/mL [150 to 3060]; median difference 143 ng/mL [95% CI 40 to 503]; p = 0.01). In the receiver operating characteristic curve analysis, D-dimer had an area under the curve of 0.71 (0.50-0.92), demonstrating weak diagnostic value. A D-dimer level of 598 ng/mL provided a sensitivity and specificity of 61% (95% CI 36% to 82%) and 74% (95% CI 62% to 83%), respectively, for diagnosing a definite or probable infection according to the ICM definitions. The specificity of detecting periprosthetic joint infection (88% [95% CI 79% to 94%]) was high when three positive serum markers (ESR, CRP, and D-dimer) were required, at the expense of sensitivity (28% [95% CI 10% to 53%]).Conclusion: In periprosthetic shoulder infection, D-dimer is elevated. However, similar to other serum tests, it has limited diagnostic utility in identifying patients with periprosthetic shoulder infection. Further work is needed to understand the process by which D-dimer is associated with active infection.Level Of Evidence: Level III, diagnostic study. [ABSTRACT FROM AUTHOR]

When antibiotic laden bone cement is used to manage periprosthetic joint infection (PJI), failure still occurs with its use in up to 30% of cases. Therefore, we designed an in vitro study to assess the bactericidal effect of N‐acetylcysteine (NAC), an antibacterial adjuvant, in cement against planktonic and biofilm forms of common PJI pathogens. NAC (10%, 20%, 30%, 40%, and 50% w/v) added to polymethyl methacrylate (PMMA) and incubated in broth at 36°C. PMMA‐alone and/or culture bacteria alone were used as a negative control. Aliquots of cement elution from each group were taken at 1 day and 1 week and then were investigated for antimicrobial efficacy against the planktonic‐form and the biofilm‐form of Staphylococcus aureus and Escherichia coli. The primary outcome was the residual colony‐forming unit count. The cytotoxicity and mechanical properties of the NAC–PMMA cement‐blocks were also assessed. NAC–PMMA efficacy against the planktonic bacteria was demonstrated at a minimum of 30% at Day 1 and a minimum of 20% at 1 week after (p <.001). NAC–PMMA cement was effective against biofilm at a minimum of 30% of NAC at 1 day and 1 week of cement immersion (p <.001). The PMMA alone group was identified as having the highest cytotoxicity (p <.001). NAC decreased the stiffness (p =.004) and maximum load breaking point of the cement (p =.029). NAC is an effective and biocompatible adjuvant to PMMA in terms of antibacterial activity against Staphylococcus aureus and Escherichia coli. The broad antibacterial spectrum of NAC, its low expense, and minimal cytotoxicity makes it an ideal agent for addition to PMMA cement. [ABSTRACT FROM AUTHOR]

Background: The process of infection and multiple procedure-related factors in 2-stage exchange arthroplasty may lead to severe bone loss that can complicate subsequent reimplantation. The primary purpose of this study is to quantitatively characterize the extent of bone loss on the femoral and acetabular side prior to reimplantation during 2-stage revision hip arthroplasty for infection.Methods: This retrospective case series includes 47 patients with planned 2-stage exchange arthroplasty for treatment of infected total hip replacement. Demographic, clinical, and surgical information, and complications during the 2-stage process were collected on all patients. The radiographs of all patients were reviewed prior to first-stage explantation and post-reimplantation or latest follow-up to characterize bone loss using the Paprosky classification systems.Results: Of the 47 patients with planned 2-stage exchange, 10 patients (21%) were not reimplanted. Following explant and spacer placement, 32 patients (68%) experienced progressive femoral bone loss, and 20 (43%) experienced progressive acetabular bone loss. Patients who experienced progression of both femoral and acetabular bone (14, 30%) had a longer time between resection and reimplantation (164 ± 128 vs 88 ± 26 days, P = .03). A reimplantation time of greater than 90 days was associated with an increased risk of combined bone loss progression (15% vs 53%, P = .01). For patients who underwent reimplantation (79%), increased bone loss led to high rates of diaphyseal femoral fixation (97%) and revision acetabular components (38%).Conclusion: Increased time to reimplantation in 2-stage exchange arthroplasty for prosthetic hip infections is associated with a high rate of acetabular and femoral bone loss, and increased complexity of reimplantation. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of periprosthetic joint infection (PJI) in the early postoperative period remains a challenge. Although studies have established that serum C-reactive protein (CRP) and synovial markers may be useful, recent studies have suggested that the current thresholds used may lack sensitivity. The purpose of this study was to examine the role of serum CRP, erythrocyte sedimentation rate (ESR), synovial fluid white blood-cell (WBC) count, and polymorphonuclear neutrophil (PMN) percentage in the diagnosis of acute postoperative PJI and to identify the optimal threshold.Methods: This multicenter study included patients who were investigated for possible PJI within 90 days of an index arthroplasty. This study included 197 patients from 4 institutions who underwent total joint arthroplasty from 2000 to 2017. Of these patients, 123 were confirmed to have PJI, and 74 were ruled out as not having PJI (non-infected group). Analyses of receiver operating characteristic (ROC) curves and the area under the curve were performed to determine the value of each test and optimal cutoff values.Results: The optimal cutoff value was 6,130 cells/μL for synovial fluid WBC count (91% sensitivity and 83% specificity), 39.8 mg/L for serum CRP (91% sensitivity and 87% specificity), 39.5 mm/hr for ESR (76% sensitivity and 67% specificity), and 79.5% for PMN percentage (95% sensitivity and 59% specificity). Reducing the acute period from 90 days to 30 days or 45 days made little difference in most threshold values. However, the optimal cutoff for synovial fluid WBC count was almost twice as high (10,170 cells/μL) when using a 30-day definition instead of a 90-day definition.Conclusions: The calculated cutoffs in our study were substantially lower than the thresholds used by the Musculoskeletal Infection Society. The calculated values of this study should be used, as previous cutoffs may be too high and lack sensitivity. In addition, it appears that the threshold values, at least for some of the tests, change as the duration since the index arthroplasty lengthens. A continuum of threshold values that is dependent on the number of days since the index arthroplasty may need to be used for the diagnosis of acute PJI.Level Of Evidence: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background The success of debridement, antibiotics, and implant retention (DAIR) in early periprosthetic joint infection (PJI) largely depends on the presence of a mature biofilm. At what time point DAIR should be disrecommended is unknown. This multicenter study evaluated the outcome of DAIR in relation to the time after index arthroplasty. Methods We retrospectively evaluated PJIs occurring within 90 days after surgery and treated with DAIR. Patients with bacteremia, arthroscopic debridements, and a follow-up <1 year were excluded. Treatment failure was defined as (1) any further surgical procedure related to infection; (2) PJI-related death; or (3) use of long-term suppressive antibiotics. Results We included 769 patients. Treatment failure occurred in 294 patients (38%) and was similar between time intervals from index arthroplasty to DAIR: the failure rate for Week 1–2 was 42% (95/226), the rate for Week 3–4 was 38% (143/378), the rate for Week 5–6 was 29% (29/100), and the rate for Week 7–12 was 42% (27/65). An exchange of modular components was performed to a lesser extent in the early post-surgical course compared with the late course (41% vs 63%, respectively; P <.001). The causative microorganisms, comorbidities, and durations of symptoms were comparable between time intervals. Conclusions DAIR is a viable option in patients with early PJI presenting more than 4 weeks after index surgery, as long as DAIR is performed within at least 1 week after the onset of symptoms and modular components can be exchanged. [ABSTRACT FROM AUTHOR]

Background: Surgical débridement, antibiotics and implant retention (DAIR) is currently recommended by international guidelines for both early acute (postsurgical) and late acute (hematogenous) periprosthetic joint infections (PJIs). However, due to a different pathogenesis of infection, a different treatment strategy may be needed.Questions/purposes: (1) Compared with early acute PJIs, are late acute PJIs associated with a higher risk of DAIR failure? (2) When stratified by microorganism, is the higher risk of failure in late acute PJI associated with Staphylocococcus aureus infection? (3) When analyzing patients with S. aureus infection, what factors are independently associated with DAIR failure?Methods: In this multicenter observational study, early acute and late acute PJIs treated with DAIR were retrospectively evaluated and matched according to treating center, year of diagnosis, and infection-causing microorganism. If multiple matches were available, the early acute PJI diagnosed closest to the late acute PJI was selected. A total of 132 pairs were included. Treatment success was defined as a retained implant during follow-up without the need for antibiotic suppressive therapy.Results: Late acute PJIs had a lower treatment success (46% [60 of 132]) compared with early acute PJIs (76% [100 of 132]), OR 3.9 [95% CI 2.3 to 6.6]; p < 0.001), but the lower treatment success of late acute PJIs was only observed when caused by Staphylococcus spp (S. aureus: 34% versus 75%; p < 0.001; coagulase-negative staphylococci: 46% versus 88%; p = 0.013, respectively). On multivariable analysis, late acute PJI was the only independent factor associated with an unsuccessful DAIR when caused by S. aureus (OR 4.52 [95% CI 1.79 to 11.41]; p < 0.001).Conclusions: Although DAIR seems to be a successful therapeutic strategy in the management of early acute PJI, its use in late acute PJI should be reconsidered when caused by Staphylococcus spp. Our results advocate the importance of isolating the causative microorganism before surgery.Level Of Evidence: Level III, therapeutic study. [ABSTRACT FROM AUTHOR]

Background: Male patients undergoing total joint arthroplasty have a higher risk of periprosthetic joint infection (PJI) compared with female patients. The exact reason for this finding is not well known. This study aimed to determine if patients with symptomatic benign prostatic hyperplasia (BPH) are at increased risk of PJI.Methods: A total of 12,902 male patients who underwent primary or revision total joint arthroplasty from January 2006 to April 2017 were retrospectively identified. The mean patient age was 62.47 years and the mean patient body mass index was 30.1 kg/m. The majority of patients were Caucasian or African American. Most surgical procedures involved the hip joints (57.8%) and were primary arthroplasties (86%). Of these patients, 386 (3%) had symptomatic BPH. Among this group, 250 patients with symptomatic BPH were identified and were matched in an approximate 1:3 ratio with 708 control patients. Using the International Consensus Meeting criteria, patients who developed PJI were identified.Results: The PJI rate was 7.9% in the symptomatic BPH group and 2.8% in the control group. Multivariate regression analysis in unmatched groups showed that symptomatic BPH was a strong independent risk factor for PJI. After matching for variables related to outcomes, symptomatic BPH remained a significant risk factor for PJI (p = 0.01).Conclusions: Patients with symptomatic BPH had a higher risk of PJI compared with the control patients. This may partly explain the higher rate of PJI that is seen in male patients.Level Of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Implementation of strategies for prevention of surgical site infection and periprosthetic joint infection is gaining further attention. We provide an overview of the pertinent evidence-based guidelines for infection prevention from the World Health Organization, the Centers for Disease Control and Prevention, and the second International Consensus Meeting on Musculoskeletal Infection. Future work is needed to ascertain clinical efficacy, optimal combinations, and the cost-effectiveness of certain measures. [ABSTRACT FROM AUTHOR]

Background: Diagnosing periprosthetic joint infection (PJI) represents a challenge that relies on multiple clinical and laboratory criteria that may not be consistently present. The synovial alpha-defensin-1 (AD-1) test has been shown to correlate accurately with the Musculoskeletal Infection Society (MSIS) criteria for the diagnosis of PJI, however, its association with persistent PJI has not been elucidated in the setting of patients receiving antibiotic spacers during second-stage reimplantation. Applying a Delphi-based consensus to define successful eradication of PJI offers an opportunity to test the utility of AD-1 in this setting.Questions/purposes: (1) Can the AD-1 test determine whether infection has been controlled using the Delphi criteria for persistent PJI as a surrogate for infection eradication during two-stage revision for PJI treatment with a spacer? (2) How does the performance of the AD-1 test compare with the MSIS criteria?Methods: This was a multicenter analysis of retrospectively collected data on patients who underwent a two-stage revision arthroplasty between May 2014 and July 2016. We included patients who had a previously confirmed PJI and received a cement spacer, underwent the second stage, had MSIS criteria data and a synovial fluid AD-1 test, and had a minimum followup of 1 year. We were unable to determine for all study sites how many patients had the test but did not meet all the criteria and so could not be studied; however, we were able to identify 69 patients (43 knees, 26 hips) who met all criteria. During the period in question, indications for use of AD-1 varied by surgeon; however, during that time, in general if a surgeon ordered it as part of the initial workup, the test would have been repeated before the second-stage reimplantation procedure. To assess the validity of AD-1 against persistence of PJI criteria at 1 year, the following were calculated using the Delphi criteria for persistent PJI as the gold standard: sensitivity, specificity, positive and negative predictive values, accuracy, and area under the curve (AUC) with 95% confidence intervals (CIs). Concordance index (c-index) and its Wald 95% CI with receiver operating characteristic (ROC) curve were calculated in relation to Delphi criteria for persistent PJI using AD-1 and then MSIS criteria. The two c-indices of AD-1 and MSIS were compared using the DeLong nonparametric approach.Results: The AD-1 test showed poor sensitivity (7%; 95% CI, 0.2-34), and poor overall accuracy (73%; 95% CI, 60-83; AUC = 0.5; 95% CI, 0.3-0.6) in detecting infection eradication at 1 year. The c-index for AD-1 versus Delphi criteria for persistent PJI was 0.519 (95% CI, 0.44-0.60), and the c-index for MSIS criteria versus Delphi criteria for persistent PJI was 0.518 (95% CI, 0.49-0.54), suggesting the weak diagnostic abilities of these models. The contrast estimate between MSIS criteria and AD-1 were not different from one another at -0.001 (95% CI%, -0.09 to 0.09; p = 0.99).Conclusions: We found that a positive synovial fluid AD-1 test correlated poorly with the presence of persistent infection 1 year after two-stage revision arthroplasty for PJI. For this reason, we recommend against the routine use of AD-1 in patients with cement spacers, until or unless future studies demonstrate that the test is more effective than we found it to be.Level Of Evidence: Level IV, diagnostic study. [ABSTRACT FROM AUTHOR]

Background Failure after a 2-stage exchange surgery for periprosthetic joint infection (PJI) is high. Previous studies demonstrated that positive cultures at reimplantation are associated with failure afterward. The aim of this multicenter study was to define the role of antibiotics in the cement spacer in relation to reimplantation cultures and subsequent failure. Methods We retrospectively evaluated 2-stage exchange procedures between 2000 and 2015. Culture-negative PJIs, cases in which no cultures were obtained during reimplantation, and cases without data on cement spacers were excluded. Results Three hundred forty-four cases were included. The rate of positive cultures during reimplantation was 9.5% for cement spacers containing a glycopeptide (27/284) (with or without an aminoglycoside) vs 21.7% for those containing monotherapy with an aminoglycoside (13/60) (P =.008), and was mostly attributed by a reduction in coagulase-negative staphylococci (CoNS) (17% vs 2%, P <.001). The failure rate was >2-fold higher at 40.0% (16/40) in cases with positive cultures at reimplantation compared to 15.8% (48/304) for those with negative cultures (P <.001). Overall, a glycopeptide in the cement spacer was not associated with a lower failure rate (18% vs 23%, P =.3), but was associated with lower failure due to CoNS (2.5% vs 13.3%, P <.001). Conclusions In a 2-stage exchange procedure for PJI, adding a glycopeptide to the cement spacer reduces the rate of positive cultures during reimplantation and is associated with a lower failure rate due to CoNS afterward. [ABSTRACT FROM AUTHOR]

Musculoskeletal infections (MSKI) remain the bane of orthopedic surgery, and result in grievous illness and inordinate costs that threaten healthcare systems. As prevention, diagnosis, and treatment has remained largely unchanged over the last 50 years, a 2nd International Consensus Meeting on Musculoskeletal Infection (ICM 2018, https://icmphilly.com) was completed. Questions pertaining to all areas of MSKI were extensively researched to prepare recommendations, which were discussed and voted on by the delegates using the Delphi methodology. The questions, including the General Assembly (GA) results, have been published (GA questions). However, as critical outcomes include: (i) incidence and cost data that substantiate the problems, and (ii) establishment of research priorities; an ICM 2018 research workgroup (RW) was assembled to accomplish these tasks. Here, we present the result of the RW consensus on the current and projected incidence of infection, and the costs per patient, for all orthopedic subspecialties, which range from 0.1% to 30%, and $17,000 to $150,000. The RW also identified the most important research questions. The Delphi methodology was utilized to initially derive four objective criteria to define a subset of the 164 GA questions that are high priority for future research. Thirty‐eight questions (23% of all GA questions) achieved the requisite > 70% agreement vote, and are highlighted in this Consensus article within six thematic categories: acute versus chronic infection, host immunity, antibiotics, diagnosis, research caveats, and modifiable factors. Finally, the RW emphasizes that without appropriate funding to address these high priority research questions, a 3rd ICM on MSKI to address similar issues at greater cost is inevitable. [ABSTRACT FROM AUTHOR]

Background: It has been demonstrated that administration of antibiotics prior to performing diagnostic testing for periprosthetic joint infection can interfere with the accuracy of the standard diagnostic tests. Therefore, the purpose of this study was to evaluate the effects of antibiotic administration prior to performing the synovial leukocyte esterase strip test for periprosthetic joint infection.Methods: We identified 121 patients who underwent revision hip or knee arthroplasty for a Musculoskeletal Infection Society (MSIS)-confirmed periprosthetic joint infection. All patients also had a leukocyte esterase strip test performed. Patients in one group (32%) took antibiotics prior to the diagnostic workup, whereas patients in another group (68%) did not receive antibiotics within 2 weeks of the diagnostic workup. The leukocyte esterase strip test, erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), synovial white blood-cell (WBC) count, and polymorphonuclear neutrophil (PMN) percentage were collected and were compared between the 2 groups.Results: The median serum ESR (85 compared with 67 mm/hr for patients who did not and did receive antibiotics; p = 0.009), CRP (16.5 compared with 12.9 mg/L; p = 0.032), synovial WBC count (45,675 compared with 9,650 cells/µL; p < 0.0001), and PMN percentage (93% compared with 88%; p = 0.004) were all significantly lower for patients receiving antibiotics. Furthermore, the administration of antibiotics resulted in a significant decrease in the sensitivity of all tests, except leukocyte esterase: ESR (79.5% in the antibiotics cohort compared with 92.7% in the no-antibiotics cohort [relative risk (RR) for false-negative results, 2.8; p = 0.04]), CRP (64.2% compared with 81.8% [RR, 1.9; p = 0.03]), WBC count (69.3% compared with 93.4% [RR, 5.0; p = 0.001]), PMN percentage (74.4% compared with 91.5% [RR, 3.0; p = 0.01]), and leukocyte esterase (78% compared with 83% [RR, 1.6; p = 0.17]). The rate of negative cultures was higher in the antibiotics group at 30.7% compared with the no-antibiotics group at 12.1% (p = 0.015).Conclusions: This current study and previous studies have demonstrated that the administration of premature antibiotics can compromise the results of standard diagnostic tests for periprosthetic joint infection, causing significant increases in false-negative results. However, in this study, the leukocyte esterase strip test maintained its performance even in the setting of antibiotic administration. Antibiotic administration prior to diagnostic workups for periprosthetic joint infection stands to interfere with diagnosis. The leukocyte esterase strip test can be used as a reliable diagnostic marker for diagnosing periprosthetic joint infection even when prior antibiotics are administered.Level Of Evidence: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: Based on current guidelines from the American Academy of Orthopaedic Surgeons (AAOS), a number of prophylactic modalities for the prevention of venous thromboembolism in total joint arthroplasty may be used. It is common practice that more potent prophylactic agents are used for patients at higher risk of venous thromboembolism. However, we are aware of no studies that have investigated the efficacy of potent anticoagulation in higher-risk individuals. Therefore, the purpose of our study was to test the hypothesis that low-molecular-weight heparin and warfarin result in a reduction in venous thromboembolism events in high-risk patients.Methods: A retrospective, multi-institutional study of 60,467 primary and revision total joint arthroplasties from 2000 to 2015 was performed. Identified medications were classified as aspirin, low-molecular-weight heparin, or warfarin. Patients with unavailable venous thromboembolism prophylaxis information or those not receiving the aforementioned prophylaxis were excluded. Information pertinent to the objective of this study was collected and a venous thromboembolism risk score was calculated based on 26 variables. Treatment outcomes assessed included 90-day rate of symptomatic venous thromboembolism and periprosthetic joint infection. Propensity score matching was performed (1:1), as well as logistic regression analysis on the total sample.Results: Aspirin prophylaxis demonstrated a lower rate of deep vein thrombosis, pulmonary embolism, and venous thromboembolism than warfarin and low-molecular-weight heparin alone throughout all risk scores. In the matched propensity score analysis, low-molecular-weight heparin and warfarin demonstrated increased odds of venous thromboembolism for both standard-risk and high-risk patients undergoing total knee arthroplasties compared with aspirin. For primary total hip arthroplasty, warfarin demonstrated an increased risk for high-risk patients and low-molecular-weight heparin demonstrated an increased risk for standard-risk patients. The prevalence of periprosthetic joint infection was higher in patients receiving warfarin (p < 0.001 for both comparisons of warfarin with aspirin and low-molecular-weight heparin).Conclusions: The results of this multi-institutional study demonstrate that the use of warfarin and low-molecular-weight heparin in higher-risk patients does not necessarily result in a reduction in symptomatic venous thromboembolism. Aspirin administered to higher-risk patients seems to be as effective as potent anticoagulation and more effective than warfarin.Level Of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: Current guidelines recommend serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as the first-line testing for evaluation of suspected periprosthetic joint infection, in addition to synovial white blood-cell (WBC) count and polymorphonuclear percentage. However, the sensitivity and other diagnostic measures of these tests using a standardized definition of periprosthetic joint infection and the influence of organisms on these inflammatory markers remain inadequately investigated.Methods: A retrospective review of an institutional database of 549 periprosthetic joint infection cases and 653 aseptic total joint arthroplasty revisions was performed. Periprosthetic joint infection was defined using major criteria from the International Consensus Meeting (ICM) on Periprosthetic Joint Infection. The mean inflammatory marker levels were compared among organisms with Student t tests and the proportions of elevated laboratory levels were compared among organisms with chi-square analyses. Receiver operating characteristic curve analyses were performed to calculate new cutoffs, sensitivities, and specificities for each organism and overall for serum CRP and ESR and synovial WBC and polymorphonuclear percentage.Results: The sensitivity of these markers for diagnosing chronic periprosthetic joint infection was 0.85 for ESR, 0.88 for CRP, 0.83 for WBC count, and 0.78 for polymorphonuclear percentage. For ESR, antibiotic-resistant organisms had higher mean values (84.3 mm/hr) than culture-negative cases (57.4 mm/hr), coagulase-negative Staphylococcus (68.3 mm/hr), and Streptococcus species (66.1 mm/hr); Staphylococcus aureus (81.0 mm/hr) was higher than culture-negative cases (57.4 mm/hr). For CRP, culture-negative cases had lower mean values (41.0 mg/L) than gram-negative organisms (87.4 mg/L), antibiotic-resistant organisms (86.0 mg/L), S. aureus (112.2 mg/L), and Streptococcus species (114.6 mg/L); S. aureus (112.2 mg/L) was higher than coagulase-negative Staphylococcus (66.0 mg/L). For WBC count, culture-negative cases had lower mean values (27,984.5 cells/mL) than S. aureus (116,250.0 cells/mL) and Streptococcus species (77,933.7 cells/mL). For polymorphonuclear percentage, there were no significant differences in mean values among all organisms.Conclusions: It appears that serological markers, namely ESR and CRP, have a higher false-negative rate than previously reported. Synovial markers similarly exhibit high false-negative rates. Furthermore, the sensitivity of these tests appears to be related to organism type. Surgeons should be aware of the high rate of false-negatives associated with low-virulence organisms and culture-negative cases.Level Of Evidence: Diagnostic Level I. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Abstract Background Periprosthetic joint infection (PJI) is a potentially deadly complication of total joint arthroplasty. This study was designed to address how the incidence of PJI and outcome of treatment, including mortality, are changing in the population over time. Methods Primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients with PJI from the 100% Medicare inpatient data set (2005-2015) were identified. Cox proportional hazards regression models for risk of PJI after THA/TKA (accounting for competing risks) or risk of all-cause mortality after PJI were adjusted for patient and clinical factors, with year included as a covariate to test for time trends. Results The unadjusted 1-year and 5-year risk of PJI was 0.69% and 1.09% for THA and 0.74% and 1.38% for TKA, respectively. After adjustment, PJI risk did not change significantly by year for THA (P =.63) or TKA (P =.96). The unadjusted 1-year and 5-year overall survival after PJI diagnosis was 88.7% and 67.2% for THA and 91.7% and 71.7% for TKA, respectively. After adjustment, the risk of mortality after PJI decreased significantly by year for THA (hazard ratio = 0.97; P <.001) and TKA (hazard ratio = 0.97; P <.001). Conclusion Despite recent clinical focus on preventing PJI, we are unable to detect substantial decline in the risk of PJI over time, although mortality after PJI has declined. Because PJI risk appears not to be changing over time, the incidence of PJI is anticipated to scale up proportionately with the demand for THA and TKA, which is projected to increase substantially in the coming decade. [ABSTRACT FROM AUTHOR]

Background: Although morbid obesity is considered a modifiable risk factor for periprosthetic joint infection (PJI), there is no consensus regarding an appropriate threshold for body mass index (BMI) above which a high risk for infection may outweigh the benefits of surgery.Questions/purposes: (1) Is there a BMI cutoff threshold that is associated with increased risk for PJI? (2) Is the risk of PJI increased in higher obesity classes?Methods: A retrospective study was conducted of all primary THAs and TKAs performed at one institution between 2006 and 2015. Overall 19,226 patients were eligible to be included in the study; 1053 patients were excluded as a result of incomplete data, resulting in a final cohort of 18,173 patients (8757 TKAs and 9416 THAs). PJI was defined using the International Consensus Meeting criteria. To ensure accurate followup, and because there is evidence to support the association between obesity and early infection, we identified PJI within 90 days of the index surgery. This relationship was examined separately for BMI as a continuous variable and for each BMI category as defined by the Centers for Disease Control and Prevention (underweight ≤ 18.49 kg/m; normal 18.5-24.9 kg/m; overweight 25-29.9 kg/m; obese class I 30-34.9 kg/m; obese class II 35-39.9 kg/m; obese class III ≥ 40 kg/m). Analyses were performed with logistic regression, accounting for both patient and surgical risk factors. A BMI threshold was evaluated with a receiver operating characteristic (ROC) curve and the Youden index.Results: The area under the ROC curve for BMI and risk of PJI within 90 days was only 0.58 (confidence interval [CI], 0.52-0.63) suggesting such a cutoff was not much better than random chance. Among the BMI classes, patients with class III obesity (≥ 40 kg/m) were the only ones showing a higher risk for PJI within 90 days (odds ratio [OR], 3.09 [1.46-6.54]; p = 0.003). The risk of developing PJI was not greater for overweight (OR, 0.72; 95% CI, 0.38-1.4), class I obese (OR, 1.06; 95% CI, 0.57-2.0), or class II obese (OR, 1.08; 95% CI, 0.52-2.2) patients. Underweight patients also demonstrated no increased risk for PJI (OR, 1.80; 95% CI, 0.23-13.9).Conclusions: The risk for infection increases gradually throughout the full range of BMI, but no threshold exists. Weight reduction before surgery may mitigate risk for infection for all patients with a BMI above normal. Of note, patients with a BMI > 40 kg/m carried a threefold higher risk for PJI and for these patients, the risks of surgery must be carefully weighed against its benefits.Level Of Evidence: Level III, therapeutic study. [ABSTRACT FROM AUTHOR]

Background: Two-stage exchange arthroplasty involves resection and reimplantation of new implants at a later stage. An antibiotic-free period is often advocated by surgeons before reimplantation. However, there is no conclusive evidence supporting the utility or duration of this practice. This study evaluated the utility and optimal duration of the antibiotic-free period before reimplantation.Methods: Electronic infection databases of 2 institutions were retrospectively reviewed from 2000 to 2014 to identify 785 patients who underwent 2-stage exchange arthroplasty, of which 409 were reimplanted without any surgeries between the first and second stage. Total joint arthroplasties that met the Musculoskeletal Infection Society criteria for periprosthetic joint infection (PJI) and had a minimum of 1-year follow-up were included. The antibiotic holiday period was defined as the time period off antibiotics before reimplantation. Treatment success was defined according to the Delphi consensus criteria. A multivariate analysis and Fisher exact test were performed.Results: The duration of the antibiotic-free period was not significantly associated with reinfection following reimplantation after controlling for potential confounders, including joint involvement, gender, institution, and comorbidities. However, the duration of spacer implantation was significantly associated with reinfection. Of the patients who failed treatment, 41.5% failed on antibiotics while 58.5% failed during the antibiotic-free period at a mean of 26.1 days.Conclusion: The duration of an antibiotic-free period does not appear to significantly affect PJI rate after reimplantation. However, many patients fail during the antibiotic-free period. Further prospective studies are needed to determine the optimal timing of reimplantation for 2-stage exchange arthroplasty for PJI treatment. [ABSTRACT FROM AUTHOR]

Background: A prior survey of members of the American Association of Hip and Knee Surgeons revealed that 78% of responding surgeons were named as a defendant in at least 1 lawsuit, and 69% of these lawsuits were dismissed or settled out of court. The most common sources of litigation were nerve injury, limb-length discrepancy, and infection. This study examined common reasons for lawsuits after total joint arthroplasty (TJA) in a single metropolitan area.Methods: A retrospective review of lawsuits filed between 2009 and 2015 in a 5-county metropolitan area was performed, including 30 hospitals and 113 TJA surgeons. Complaints underwent a manual review to determine the number of lawsuits and the specific allegations filed against each surgeon.Results: Thirty-one (27.4%) surgeons were named as a defendant in at least 1 lawsuit. Eighty-three total lawsuits were filed during the period, 50 of which were dismissed or settled outside of court. Top reasons for lawsuits were, in descending order, infection, nerve injury, chronic pain, vascular injury, periprosthetic fracture, retention of foreign body, dislocation, limb-length discrepancy, venous thromboembolism, loosening, compartment syndrome, and other medical complaints.Conclusion: Infection appears to be the basis of most lawsuits after TJA. Surgeons should be aware of the potential for a lawsuit for complications and should strive to better communicate with patients regarding preoperative informed consent and disclosure after adverse events. Surgeons should minimize performing surgery in patients at high risk of complications, such as patients with a higher likelihood of developing postoperative infection or patients on chronic pain medications. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of periprosthetic joint infection (PJI) can be made when 1 major criterion or 3 of 5 minor criteria are present. However, the outcomes of patients with a major vs minor criteria for diagnosis have not been studied. The objective of this study was to evaluate if a difference in outcome of surgical intervention existed between patients with PJI who were diagnosed with a major criterion or a combination of minor criteria.Methods: A retrospective chart review identified 277 primary total hip or knee arthroplasty patients who had developed PJI based on the International Consensus Meeting definition. Patients were further stratified into "major" vs "minor" groups. Patient demographics, PJI workup, surgical treatment, microbiological growth, and clinical outcomes were recorded. Treatment success was defined by using the Delphi criteria. Standard statistical analysis was performed.Results: Overall, 34 patients met minor-only criteria (12.2%), whereas 243 met major criteria. Of the minor-only patients, 16 (47%) were culture negative. When controlling for confounding variables, there was no statistically significant difference with regard to treatment success (minor 94.1% vs major 82.3%, P = .085) between groups at final follow-up (mean 110 months, range 2.3-567 months). Only higher Charlson comorbidity index (P = .001) and an initial 2-stage surgical procedure (P = .003) were associated with decreased treatment success.Conclusion: PJI patients were similar between both criteria groups, and there was no difference in treatment success as defined by the Delphi criteria between minor-only PJI and major criteria PJI patients. [ABSTRACT FROM AUTHOR]

Background: Preoperative identification of patients at risk for periprosthetic joint infection (PJI) following total hip arthroplasty (THA) or total knee arthroplasty (TKA) is important for patient optimization and targeted prevention. The purpose of this study was to create a preoperative PJI risk calculator for assessing a patient's individual risk of developing (1) any PJI, (2) PJI caused by Staphylococcus aureus, and (3) PJI caused by antibiotic-resistant organisms.Methods: A retrospective review was performed of 27,717 patients (12,086 TKAs and 31,167 THAs), including 1,035 with confirmed PJI, who were treated at a single institution from 2000 to 2014. A total of 42 risk factors, including patient characteristics and surgical variables, were evaluated with a multivariate analysis in which coefficients were scaled to produce integer scores. External validation was performed with use of data on 29,252 patients who had undergone total joint arthroplasty (TJA) at an independent institution.Results: Of the 42 risk factors studied, 25 were found not to be significant risk factors for PJI. The most influential of the remaining 17 included a previous open surgical procedure, drug abuse, a revision procedure, and human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). The areas under the curves were 0.83 and 0.84 for any PJI, 0.86 and 0.83 for antibiotic-resistant PJI, and 0.86 and 0.73 for S. aureus PJI in the internal and external validation models, respectively. The rates of PJI were 0.56% and 0.61% in the lowest decile of risk scores and 15.85% and 20.63% in the highest decile.Conclusions: In this large-cohort study, we were able to identify and validate risk factors and their relative weights for predicting PJI. Factors such as prior surgical procedures and high-risk comorbidities should be considered when determining whether TJA is indicated and when counseling patients.Level Of Evidence: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: Next-generation sequencing is a well-established technique for sequencing of DNA and has recently gained attention in many fields of medicine. Our aim was to evaluate the accuracy of next-generation sequencing in identifying the causative organism(s) in patients with periprosthetic joint infection.Methods: In this prospective study, samples were collected from 65 revision arthroplasties (39 knees and 26 hips) and 17 primary arthroplasties (9 hips and 8 knees). Synovial fluid, deep tissue, and swabs were obtained at the time of the surgical procedure and were shipped to the laboratory for next-generation sequencing. Deep-tissue specimens were also sent to the institutional laboratory for culture. Sensitivity and specificity were calculated for next-generation sequencing, using the Musculoskeletal Infection Society (MSIS) definition of periprosthetic joint infection as the standard.Results: In 28 revisions, the cases were considered to be infected; cultures were positive in 17 cases (60.7% [95% confidence interval (CI), 40.6% to 78.5%]), and next-generation sequencing was positive in 25 cases (89.3% [95% CI, 71.8% to 97.7%]), with concordance between next-generation sequencing and culture in 15 cases. Among the 11 cases of culture-negative periprosthetic joint infection, next-generation sequencing was able to identify an organism in 9 cases (81.8% [95% CI, 48.2% to 97.7%]). Next-generation sequencing identified microbes in 9 (25.0% [95% CI, 12.1% to 42.2%]) of 36 aseptic revisions with negative cultures and in 6 (35.3% [95% CI, 14.2% to 61.7%]) of 17 primary total joint arthroplasties. Next-generation sequencing detected several organisms in most positive samples. However, in the majority of patients who were infected, 1 or 2 organisms were dominant.Conclusions: Next-generation sequencing may be a useful adjunct in identification of the causative organism(s) in culture-negative periprosthetic joint infection. Our findings suggest that some cases of monomicrobial periprosthetic joint infection may have additional organisms that escape detection when culture is used. Further study is required to determine the clinical implications of isolated organisms in samples from patients who are not thought to be infected.Level Of Evidence: Diagnostic Level I. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: For patients with failed surgical treatment of an infected TKA, salvage operations such as arthrodesis or above-knee amputation (AKA) may be considered. Clinical and institutional factors associated with AKA and arthrodesis after a failed TKA have not been investigated in a large-scale population, and the utilization rate and trend of these measures are not well known.Questions/purposes: (1) How has the frequency of arthrodesis and AKA after infected TKA changed over the last 10 years? (2) What clinical or institutional factors are associated with patients undergoing arthrodesis or AKA? (3) What is the risk of mortality after arthrodesis or AKA?Methods: The Medicare 100% National Inpatient Claims Database was used to identify 44,466 patients 65 years of age or older who were diagnosed with an infected TKA and who underwent revision between 2005 and 2014 based on International Classification of Diseases, 9th Revision, Clinical Modification codes. Overall, 1182 knee arthrodeses and 1864 AKAs were identified among the study population. One year of data before the index infection-related knee revision were used to examine patient demographic, institutional, and clinical factors, including comorbidities, hospital volumes, and surgeon volumes. We developed Cox regression models to investigate the risk of arthrodesis, AKA, and death as outcomes. In addition, the year of the index revision was included as a covariate to determine if the risk of subsequent surgical interventions was changing over time. The risk of mortality was also assessed as the event of interest using a similar multivariate Cox model for each patient group (arthrodesis, AKA) in addition to those who underwent additional revisions but who did not undergo either of the salvage procedures.Results: The number of arthrodesis (hazard ratio [HR], 0.90, p < 0.001) and amputation (HR, 0.95, p < 0.001) procedures showed a declining trend. Clinical factors associated with arthrodesis included acute renal failure (HR, 1.22 [1.06-1.41], p = 0.006), obesity (HR, 1.58 [1.35-1.84], p < 0.001), and having additional infection-related revisions (HR for 2+ additional revisions, 1.36 [1.13-1.64], p = 0.001). Higher Charlson comorbidity score (HR for a score of 5+ versus 0, 2.56 [2.12-3.14], p < 0.001), obesity (HR, 1.14 [1.00-1.30], p = 0.044), deep vein thrombosis (HR, 1.34 [1.12-1.60], p = 0.001), and additional revisions (HR for 2+ additional revisions, 2.19 [1.91-2.49], p < 0.001) were factors associated with AKA, which in turn was an independent risk factor for mortality. The risk of death increased with amputation after adjusting for age, comorbidities, and other factors (HR, 1.28 [1.20-1.37], p < 0.001), but patients who received arthrodesis did not show a change in mortality compared with the patients who did not receive arthrodesis or amputation (HR, 1.00 [0.91-1.10], p = 0.971).Conclusions: The findings of this study suggest that clinicians may be more aggressively attempting to preserve the knee even in the face of chronic prosthetic joint infection but also show that a greater number of revisions is associated with a greater risk of subsequent AKA or arthrodesis. The results also suggest that recommending centers with a high volume of joint arthroplasties may be a way to reduce the risk of the salvage procedures.Level Of Evidence: Level III, therapeutic study. [ABSTRACT FROM AUTHOR]

Background: Despite the availability of a battery of tests, the diagnosis of periprosthetic joint infection (PJI) continues to be challenging. Serum D-dimer assessment is a widely available test that detects fibrinolytic activities that occur during infection. We hypothesized that patients with PJI may have a high level of circulating D-dimer and that the presence of a high level of serum D-dimer may be a sign of persistent infection in patients awaiting reimplantation.Methods: This prospective study was initiated to enroll patients undergoing primary and revision arthroplasty. Our cohort consisted of 245 patients undergoing primary arthroplasty (n = 23), revision for aseptic failure (n = 86), revision for PJI (n = 57), or reimplantation (n = 29) or who had infection in a site other than a joint (n = 50). PJI was defined using the Musculoskeletal Infection Society criteria. In all patients, serum D-dimer level, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level were measured preoperatively.Results: The median D-dimer level was significantly higher (p < 0.0001) for the patients with PJI (1,110 ng/mL [range, 243 to 8,487 ng/mL]) than for the patients with aseptic failure (299 ng/mL [range, 106 to 2,571 ng/mL). Using the Youden index, 850 ng/mL was determined as the optimal threshold value for serum D-dimer for the diagnosis of PJI. Serum D-dimer outperformed both ESR and serum CRP, with a sensitivity of 89% and a specificity of 93%. ESR and CRP had a sensitivity of 73% and 79% and a specificity of 78% and 80%, respectively. The sensitivity and specificity of ESR and CRP combined was 84% (95% confidence interval [CI], 76% to 90%) and 47% (95% CI, 36% to 58%), respectively.Conclusions: It appears that serum D-dimer is a promising marker for the diagnosis of PJI. This test may also have a great utility for determining the optimal timing of reimplantation.Level Of Evidence: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: There is a paucity of data regarding the threshold of synovial fluid white blood-cell (WBC) count and polymorphonuclear cell (neutrophil) percentage of the WBC count (PMN%) for the diagnosis of chronic periprosthetic joint infection (PJI) after total hip arthroplasty. Despite this, many organizations have provided guidelines for the diagnosis of PJI that include synovial fluid WBC count and PMN%. We attempted to define a threshold for synovial fluid WBC count and PMN% for the diagnosis of chronic PJI of the hip using a uniform definition of PJI and to investigate any variations in the calculated thresholds among institutions.Methods: From 4 academic institutions, we formed a cohort of 453 patients with hip synovial fluid cell count analysis as part of the work-up for revision total hip arthroplasty. Using the definition of PJI from the Musculoskeletal Infection Society (MSIS), 374 joints were diagnosed as aseptic and 79, as septic. Intraoperative aspirations were performed as routine practice, regardless of the suspicion for infection, in 327 (72%) of the patients. Using receiver operating characteristic curves, the optimal threshold values for synovial WBC count and PMN% were identified.Results: For the diagnosis of chronic PJI of the hip, the threshold for the overall cohort was 3,966 cells/μL for WBC count and 80% for PMN%. Despite the high predictive accuracy for the cohort, there was notable institutional variation in fluid WBC count and PMN%. Furthermore, the rate of PJI was 14% (4 of 28) for patients with a WBC count of 3,000 to 5,000 cells/μL compared with 91% (20 of 22) for patients with a WBC count of >50,000 cells/μL. Similarly, the rate of PJI was 29% (14 of 49) for patients with a PMN% of 75% to 85% compared with 69% (33 of 48) for patients with a PMN% of >95%.Conclusions: Using the MSIS criteria, the optimal synovial fluid WBC count and PMN% to diagnose chronic PJI in the hip is closer to thresholds for the knee than those previously reported for the hip. This study validates the diagnostic utility of synovial fluid analysis for the diagnosis of periprosthetic hip infection; however, we also identified a clinically important "gray area" around the threshold for which the presence of PJI may be unclear.Level Of Evidence: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: The treatment outcomes of periprosthetic joint infection are frequently dependent on characteristics of the causative organism. The objective of this comparative study was to investigate the prevalence of and risk factors for development of polymicrobial periprosthetic joint infection, and the outcome of surgical treatment of these patients.Methods: All patients with polymicrobial, monomicrobial, or culture-negative periprosthetic joint infection treated from 2000 to 2014 were identified at a single institution. Ninety-five patients with a polymicrobial periprosthetic joint infection had a minimum follow-up of 12 months. We matched patients with a polymicrobial periprosthetic joint infection with the other cohorts using propensity score matching for several important parameters. Treatment success was defined according to the Delphi criteria; Kaplan-Meier survivorship curves were generated to demonstrate this. A multiple logistic regression analysis was performed to determine risk factors for a polymicrobial periprosthetic joint infection.Results: Overall, 10.3% (108 of 1,045) of the periprosthetic joint infections treated at our institution were polymicrobial in nature. Patients with a polymicrobial periprosthetic joint infection had a higher failure rate at 50.5% (48 of 95) compared with the monomicrobial periprosthetic joint infection cohort at 31.5% (63 of 200) and the culture-negative periprosthetic joint infection cohort at 30.2% (48 of 159) (p = 0.003). The survivorship of the polymicrobial periprosthetic joint infection group was 52.2% at the 2-year follow-up, 49.3% at the 5-year follow-up, and 46.8% at the 10-year follow-up. Patients with polymicrobial periprosthetic joint infection had a higher rate of amputation (odds ratio [OR], 3.80 [95% confidence interval (CI), 1.34 to 10.80]), arthrodesis (OR, 11.06 [95% CI, 1.27 to 96.00]), and periprosthetic joint infection-related mortality (OR, 7.88 [95% CI, 1.60 to 38.67]) compared with patients with monomicrobial periprosthetic joint infection. Isolation of gram-negative organisms (p < 0.01), enterococci (p < 0.01), Escherichia coli (p < 0.01), and atypical organisms (p < 0.01) was associated with polymicrobial periprosthetic joint infection. Only the presence of a sinus tract (OR, 2.20 [95% CI, 1.39 to 3.47]; p = 0.001) was a significant risk factor for polymicrobial periprosthetic joint infection on multivariate analysis.Conclusions: This study reveals that polymicrobial periprosthetic joint infection, occurring at a relatively low rate, is associated with poor outcomes when compared with monomicrobial and culture-negative periprosthetic joint infection. Patients with polymicrobial infections were more likely to require a salvage procedure or to have periprosthetic joint infection-related mortality. Polymicrobial periprosthetic joint infection was associated with soft-tissue defects such as a sinus tract and certain types of organisms, which should be considered when administering antibiotics to these patients.Level Of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic renal failure (CRF) may require total joint arthroplasty (TJA) to treat degenerative joint disease, fractures, osteonecrosis, or amyloid arthropathy. There have been conflicting results, however, regarding outcomes of TJA in patients with chronic renal disease. The aim of this case-controlled study was to determine the outcome of TJA in patients with CRF, with particular interest in the incidence of infections and inhospital mortality.Methods: We queried our electronic database to determine which patients among the 29,389 TJAs performed at our institution between January 2000 and June 2012 had a diagnosis of CRF. A total of 359 CRF patients were identified and matched for procedure, gender, age (±4 years), date of surgery (±2 years), and body mass index (±5 kg/m2) in a 2:1 ratio to 718 control patients.Results: The incidence of infection and inhospital mortality was not significantly different between the nondialysis CRF patients and controls, whereas it was significantly higher in dialysis-dependent end-stage renal failure patients compared to controls. Of the 50 CRF patients receiving hemodialysis, 10 (20%) developed surgical site infection, of which 4 (8%) were periprosthetic joint infection, and 4 (8%) died during hospital stay. The odds ratio for infection in the dialysis group was 7.54 (95% confidence interval: 2.83-20.12) and 10.46 (95% confidence interval: 1.67-65.34) for the inhospital mortality.Conclusion: We conclude that end-stage renal failure patients receiving hemodialysis have higher postoperative infection and inhospital mortality rates after an elective TJA procedure, whereas nondialysis CRF patients have similar outcomes compared with the general TJA population. [ABSTRACT FROM AUTHOR]

Periprosthetic joint infection (PJI) is one of the most serious complications after total joint arthroplasty (TJA). The prevalence of urinary tract infection (UTI) is common, particularly among elderly women, a group for whom TJA may be required. The association between preoperative UTI and increased risk of PJI after TJA is unclear. We reviewed key articles concerning the relationship between UTIs and PJI, and summarized recommendations of international consensus on PJI, which was established in Philadelphia in July of 2018. In addition, we distinguish between symptomatic UTI and asymptomatic bacteriuria, because their causative effects on PJI are quite different. [ABSTRACT FROM AUTHOR]

Question: In patients with periprosthetic joint infection (PJI) managed by surgery, is 6 versus 12 weeks of antibiotic therapy noninferior for persistent infection at 2 years after the end of antibiotic therapy? Graph TABLE I 6 versus 12... Conclusion: In patients with PJI managed by surgery, 6 versus 12 weeks of antibiotic therapy increased persistent infection at 2 years after end of therapy. [Extracted from the article]

Background: It is strongly recommended that tissue and synovial fluid culture samples be obtained during reimplantation performed as part of a 2-stage exchange arthroplasty. The rate of positive cultures during reimplantation and the influence of positive cultures on subsequent outcomes, to our knowledge, are unknown. This study was designed to determine the rate of positive cultures during reimplantation and to investigate the association between positive cultures at reimplantation and subsequent outcomes.Methods: We retrospectively reviewed the data of 259 patients who met the Musculoskeletal Infection Society criteria for periprosthetic joint infection (PJI) and who underwent both stages of 2-stage exchange arthroplasty at our institution from 1999 to 2013. Among these patients were 267 PJIs (186 knees and 81 hips); 33 (12.4%) had ≥1 positive culture result at reimplantation. Treatment failure was assessed according to the Delphi-based consensus definition. Logistic regression analysis was performed to assess the predictors of positive culture and risk factors for failure of 2-stage exchange arthroplasty.Results: Of the 33 cases with PJI, 15 (45.5%) had a subsequent failure of the 2-stage exchange arthroplasty compared with 49 (20.9%) of the cases that were culture-negative at reimplantation. When controlling for other variables using multivariate analyses, the risk of treatment failure was higher (odds ratio = 2.53; 95% confidence interval [CI] = 1.13 to 5.64) and reinfection occurred earlier (hazard ratio = 2.00; 95% CI = 1.05 to 3.82) for the cases with a positive culture during reimplantation. The treatment failure rate did not differ (p = 0.73) between cases with ≥2 positive cultures (36.4%) and 1 positive culture (50%).Conclusions: Positive intraoperative culture at the time of reimplantation, regardless of the number of positive samples, was independently associated with >2 times the risk of subsequent treatment failure and earlier reinfection. Surgeons should be aware that a positive culture at the time of reimplantation independently increases the risk of subsequent failure.Level Of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: Although thyroxine has an important role in modulating the immune system, it has not been associated with periprosthetic joint infection. This study was conceived to examine the association between hypothyroidism and periprosthetic joint infection (PIJ).Methods: Using an institutional database, the preoperative comorbidities of 32,289 total joint arthroplasties performed between 2000 and 2013 were identified using an International Classification of Diseases, Ninth Revision-based comorbidity index.Results: In the multivariate analysis, hypothyroidism was found to be an independent risk factor (adjusted odds ratio: 2.46; P < .0001). In addition, patients who developed PJI demonstrated higher thyroid-stimulating hormone levels than those without (P = .04).Discussion: Surgeons should be aware of this increased risk of PJI in hypothyroid patients when risk stratifying, and future studies are needed to determine the potential role of thyroxine supplementation. [ABSTRACT FROM AUTHOR]

Background: Two-stage exchange arthroplasty remains the preferred method to treat periprosthetic joint infection. The aim of this study was to investigate the clinical course of periprosthetic joint infection following resection arthroplasty and insertion of a spacer.Methods: Our institutional database was used to identify 504 cases of periprosthetic joint infection (326 knees and 178 hips) treated with resection arthroplasty and spacer insertion as part of a two-stage exchange arthroplasty. A review of the patient charts was performed to extract information relevant to the objectives of this study that included the details of the clinical course following resection arthroplasty.Results: The mean follow-up duration after initial spacer implantation was 56.2 months. Reimplantation occurred in the joints of 417 (82.7%) of 504 cases. Of these 417 cases, 329 (78.9%) had a minimum one-year follow-up, and 81.4% of these had successful treatment. The mean duration from resection arthroplasty to reimplantation was 4.2 months (range, 0.7 to 131.7 months). Sixty (11.9%) of the 504 joints required interim spacer exchange(s). Of the eighty-seven cases that did not undergo reimplantation, six (6.9%) required amputation, five (5.7%) underwent a Girdlestone procedure, four (4.6%) underwent arthrodesis, and seventy-two (82.8%) underwent spacer retention. Thirty-six patients died in the interstage period.Conclusions: The commonly held belief that two-stage exchange arthroplasty carries a high success rate for the eradication of periprosthetic joint infection may need to be reexamined. A considerable number of patients undergoing the first stage of a two-stage procedure do not undergo a subsequent reimplantation for a variety of reasons or require an additional spacer exchange in the interim. Reports on the success of two-stage exchange should account for the mortality of these patients and for patients who never undergo reimplantation. [ABSTRACT FROM AUTHOR]

Despite the battery of available tests, the diagnosis of periprosthetic joint infection (PJI) remains a challenge. A comprehensive medical history and physical examination with appropriate radiographs followed by erythrocyte sedimentation rate and serum C-reactive protein are the first-line screening test for patients with suspected hip PJI. The second line of investigation of patients with abnormal serology or a strong suspicion for PJI, is joint aspiration. Aspirates should be sent for assessment of white blood cell count, polymorphonuclear percentage, leukocyte esterase strip test, and microbiology. If the first attempt fails, the joint should be re-aspirated at a different time. The International Consensus recommends against infiltration of saline or other fluids into a “dry” joint. In patients not planned for surgery but need further evaluation for PJI, a nuclear imaging study may help. In others with a planned revision surgery, intraoperative samples for frozen section and culture study are the best measures available. Treatment strategies for PJI are well established in the literature. Poor surgical candidates receive oral suppressive antibiotic therapy alone. Acute PJI, presenting within 4 weeks of the index surgery, or as a result of bacteraemia, may be treated with irrigation and debridement and implant retention. Chronic PJI, occurring more than 4 weeks after initial surgery, is treated with 1-stage or 2-stage revision arthroplasty. In some persistent infections or patients who refuse to undergo revision surgery, salvage procedures may be needed. [ABSTRACT FROM AUTHOR]

Prosthetic joint infection (PJI) is a calamitous complication with high morbidity and substantial cost. The reported incidence is low but it is probably underestimated due to the difficulty in diagnosis. PJI has challanged the orthopaedic community for several years and despite all the advances in this field, it is still a real concern with immense impact on patients, and the healthcare system. Numerous factors can predispose patients to PJI. In this review we have summarized the effective prevention strategies along with the recommendations of a recent International Consensus Meeting on Surgical Site and Periprosthetic Joint Infection. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "If, When, and How to Use Rifampin in Acute Staphylococcal Periprosthetic Joint Infections, a Multicentre Observational Study."

Background: Acute postoperative infection after total hip arthroplasty (THA) is typically treated with irrigation and débridement and exchange of the modular femoral head and acetabular liner. Given a rate of failure exceeding 50% in some series, a one-stage exchange has been suggested as a potential alternative because it allows more thorough débridement and removal of colonized implants. To date, most studies published on the one-stage exchange have used microbe-specific antibiotic-laden bone cement with only one small single-institution series that reported outcomes after a cementless one-stage exchange.Questions/purposes: We determined whether a one-stage cementless exchange for treating acute postoperative infection after THA would result in infection control with component retention and normalization of infection markers.Methods: We retrospectively identified 27 patients who underwent a one-stage exchange performed for an acute (≤6 weeks) postoperative infection after THA from April 2004 to December 2009. Primary cementless components were used both at the time of the index arthroplasty and the revision in all patients. Surgery was followed by a 6-week course of culture-specific antibiotics in all patients and a variable course of oral antibiotics. Our primary outcome was retention of the implants at most recent followup and our secondary outcome was normalization of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) at most recent followup. Patients were followed until failure or a minimum of 2 years.Results: At a minimum followup of 27 months (mean, 50 months; range, 27-89 months), 19 of the 27 patients (70%) retained their implants but four required further operative débridement with component retention at a mean of 3 weeks (range, 2-6 weeks) to obtain control of infection. Thus, an isolated single-stage exchange was successful in 15 of the 27 patients (56%). Eight patients (30%) ultimately had a two-stage exchange for persistent infection; seven of these patients required no further surgery, whereas one patient required a second two-stage exchange. Of those patients retaining their prosthesis after one-stage exchange and tracked with ESR and CRP, four (33% [four of 12]) had elevated values without other signs or symptoms of recurrent infection.Conclusions: For acute postoperative infection after primary THA, a one-stage cementless exchange allowed 70% of patients to retain their implants at most recent followup. Of those patients who ultimately went on to a two-stage exchange, only one required a second two-stage exchange.Level Of Evidence: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]