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Background: The accuracy of intraoperative periprosthetic frozen section histologic evaluation in predicting a diagnosis of periprosthetic joint infection prior to microbiologic culture results is unknown.Methods: We performed a systematic review and meta-analysis of all longitudinal studies that compared frozen section histologic results with simultaneously obtained microbiologic culture at the time of revision total hip or total knee arthroplasty. The data sources were Ovid MEDLINE, Ovid EMBASE, the Cochrane Library, ISI Web of Science, and SCOPUS, from the inception of each database to January 2010.Results: Twenty-six studies involving 3269 patients undergoing revision hip or knee arthroplasty met the inclusion criteria. A culture-positive periprosthetic joint infection was confirmed in 796 (24.3%) of the patients. Frozen section results, using any of the diagnostic criteria chosen by the investigating pathologist, had a pooled diagnostic odds ratio of 54.7 (95% confidence interval [CI], 31.2 to 95.7), a likelihood ratio of a positive test of 12.0 (95% CI, 8.4 to 17.2), and a likelihood ratio of a negative test of 0.23 (95% CI, 0.15 to 0.35) for the diagnosis of periprosthetic joint infection. Fifteen studies utilizing a threshold of five polymorphonuclear leukocytes (PMNs) per high-power field to define a positive frozen section had a diagnostic odds ratio of 52.6 (95% CI, 23.7 to 116.2), and six studies utilizing a diagnostic threshold of ten PMNs per high-power field had a diagnostic odds ratio of 69.8 (95% CI, 33.6 to 145.0). There was no significant difference between the diagnostic odds ratio or likelihood ratios associated with these thresholds. The moderate to high heterogeneity among the included studies was unexplained by variability in the study design, diagnostic criteria for acute inflammation, reference standard for periprosthetic joint infection, or prevalence of infection. This heterogeneity could be due to differences in the inclusion and exclusion criteria, tissue sampling error, experience or technique of the pathologists, number of microscopic fields visualized, and field diameter examined.Conclusions: Intraoperative frozen sections of periprosthetic tissues performed well in predicting a diagnosis of culture-positive periprosthetic joint infection but had moderate accuracy in ruling out this diagnosis. Frozen section histopathology should therefore be considered a valuable part of the diagnostic work-up for patients undergoing revision arthroplasty, especially when the potential for infection remains after a thorough preoperative evaluation. The optimum diagnostic threshold (number of PMNs per high-power field) required to distinguish periprosthetic joint infection from aseptic failure could not be discerned from the included studies. There was no significant difference between the diagnostic accuracy of frozen section histopathology utilizing the most common thresholds of five or ten PMNs per high-power field. [ABSTRACT FROM AUTHOR]

Purpose: Limited data exist regarding the long-term results or risk factors for failure after two-stage reimplantation for periprosthetic knee infection. The purpose of this retrospective review was to investigate infection-free implant survival and identify variables associated with reinfection after this procedure. Furthermore, a staging system was evaluated as a possible prognostic tool for patients undergoing two-stage reimplantation of infected total knee arthroplasty (TKA).Methods: In this level II, retrospective prognostic study, 368 patients with infected TKA treated with a two-stage revision protocol at our institution between 1998 and 2006 were reviewed. Patients who developed recurrent infection and an equal number of patients randomly selected for the control group were analysed for risk factors associated with treatment failure.Results: At the most recent follow-up, 58 (15.8%) patients had developed reinfection after the two-stage reimplantation. The median time to reinfection was 1,303 days (3.6 years), with follow-up time ranging from six to 2,853 days (7.8 years). The strongest positive predictors of treatment failure included chronic lymphoedema [hazard ratio (HR) = 2.28, 95% confidence interval (CI) 1.16-4.48; p = 0.02),and revision between resection and definitive reimplantation (HR = 2.13, 95% CI 1.20-3.79; p = 0.01, whereas patients treated with intravenously administered Cefazolin had a significant reduction in recurrent infection rate (HR = 0.48, 95% CI 0.25-0.90; p = 0.02).Conclusions: Our findings should be of help in counselling patients regarding their prognosis when faced with two-stage exchange for infected TKA and provide a basis for future comparisons. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the clinical and bacteriological efficacy and the safety and tolerability profile of linezolid when used as the primary component of a combined surgical and antimicrobial treatment strategy for orthopedic infections. PATIENTS AND METHODS: We retrospectively reviewed medical records to obtain clinical, bacteriological, and safety outcomes of 20 consecutive patients who took linezolid for the treatment of orthopedic infections between April 1, 2000, and November 30, 2002. RESULTS: Twenty patients received linezolid therapy for microbiologically confirmed orthopedic infections due to gram-positive cocci during the 32-month study period. Fifteen patients (75%) had infections involving orthopedic hardware; in 10 of these patients, the hardware was removed. All 20 patients underwent surgical débridement. At a mean follow-up of 276 days, 11 patients (55%) achieved clinical cure, 7 (35%) had clinical improvement but received long-term antimicrobial suppressive therapy, 1 (5%) had clinical relapse after discontinuing linezolid treatment, and 1 (5%) died of a cause unrelated to linezolid treatment. Bacterial persistence was documented in 3 patients (15%), all of whom were Infected with methicillin-resistant Staphylococcus aureus. Eight patients (40%) developed reversible myelosuppression, 1 (5%) had irreversible peripheral neuropathy, and 2 (10%) discontinued linezolid treatment because of pancytopenia or urticaria. CONCLUSION: Oral linezolid may be an effective alternative therapy for orthopedic infections due to linezolid-susceptible gram-positive bacteria in patients who are unable to take other antimicrobial drugs because of drug allergy or Intolerance or antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to review the results and complications of treatment of simultaneous infection of both knees after bilateral total knee arthroplasty.Methods: Between 1976 and 1999, twenty-one patients with a mean age of seventy-one years were treated for simultaneous infection of both knees after bilateral total knee arthroplasty. Two patients died within two years, and one patient was lost to follow-up after one year. The remaining eighteen patients were followed for a mean of five years. At the time of presentation, all twenty-one patients had had symptoms for less than three weeks. Eleven patients (twenty-two knees) were treated with attempts at prosthetic salvage with surgical débridement and administration of suppressive antibiotics. Resection arthroplasty was performed as the initial treatment in ten patients (twenty knees).Results: Of the ten patients treated with initial resection, seven patients (fourteen knees) underwent subsequent reimplantation. All fourteen knees were functioning well at the time of the latest follow-up, and none had been revised at a mean of two years after reimplantation. Of the eleven patients (twenty-two knees) who had been initially treated with prosthetic salvage, nine patients (eighteen knees) had a recurrence of the infection that required a reoperation (bilateral resection arthroplasty in seven patients, bilateral above-the-knee amputation in one patient, and repeat débridement of both knees in one patient). Two of the seven patients who had resection underwent reimplantation six weeks postoperatively, and the other five patients (ten knees) did not have reimplantation because of low functional demands and prohibitive medical comorbidity.Conclusion: We believe that treatment of simultaneous infection of both knees after bilateral total knee arthroplasty should consist of bilateral resection arthroplasty and delayed reimplantation after a period of intravenous administration of organism-specific antibiotics. [ABSTRACT FROM AUTHOR]

Antimicrobial prophylaxis is commonly used by clinicians for the prevention of numerous infectious diseases, including herpes simplex infection, rheumatic fever, recurrent cellulitis, meningococcal disease, recurrent uncomplicated urinary tract infections in women, spontaneous bacterial peritonitis in patients with cirrhosis, influenza, infective endocarditis, pertussis, and acute necrotizing pancreatitis, as well as infections associated with open fractures, recent prosthetic joint placement, and bite wounds. Perioperative antimicrobial prophylaxis is recommended for various surgical procedures to prevent surgical site infections. Optimal antimicrobial agents for prophylaxis should be bactericidal, nontoxic, inexpensive, and active against the typical pathogens that can cause surgical site infection postoperatively. To maximize its effectiveness, intravenous perioperative prophylaxis should be administered within 30 to 60 minutes before the surgical incision. Antimicrobial prophylaxis should be of short duration to decrease toxicity and antimicrobial resistance and to reduce cost. [ABSTRACT FROM AUTHOR]

Since first described In 1961, methicillin-resistant Staphylococcus aureus (MRSA) has become a common nosocomial pathogen. Substantial increases in MRSA infections among nonhospitalized patients are being reported. Methicillin-resistant S. aureus is the most common isolate from skin and soft tissue infections in selected centers in the United States. Community-acquired MRSA strains differ from nosocomial strains in clinically relevant ways, such as in their propensity to cause skin and soft tissue infection and severe necrotizing pneumonia. Clinicians in numerous specialties, particularly primary care physicians, will likely evaluate patients presentIng with community-acquired MRSA and should become familiar with the epidemiology and clinical characteristics of and evolving therapeutic and preventive strategies for this infection. [ABSTRACT FROM AUTHOR]

Background: Periprosthetic joint infection (PJI) is an uncommon, but serious complication in total joint arthroplasty. Personalized risk prediction and risk factor management may allow better preoperative assessment and improved outcomes. We evaluated different data-driven approaches to develop surgery-specific PJI prediction models using large-scale data from the electronic health records., Methods: A large institutional arthroplasty registry was leveraged to collect data from 58,574 procedures of 41,844 patients who underwent at least one primary and/or revision hip and/or knee arthroplasty between 2000 and 2019. The registry dataset was augmented with additional clinical, procedural, and laboratory data from the electronic health records for more than 100 potential predictor variables. The main outcome was PJI within the first year after surgery. We implemented both traditional and machine learning methods for model development (lasso regression, relaxed lasso regression, ridge regression, random forest, stepwise regression, extreme gradient boosting, neural network) and used 10-fold cross-validation to calculate measures of model performance in terms of discrimination (c-statistic), cross-entropy loss, and calibration., Results: All models performed similarly in predicting PJI risk, with negligible differences of less than 0.08 between the best and worst-performing models. The relaxed and fully relaxed lasso models using the Cox model structure outperformed the other models with concordances of 0.787 in primary hip arthroplasty and 0.722 in revision hip arthroplasty, with the number of predictors ranging from nine to 41. The concordances with the relaxed lasso models were 0.681 in primary and 0.699 in revision knee arthroplasty, with a higher number of predictors in the models. Predictors included in the models varied substantially across the four surgical groups., Conclusions: The incorporation of additional data from the electronic health records offers limited improvement in PJI risk stratification. Furthermore, improvement in PJI risk prediction was modest with the machine learning approaches and may not justify the added complexity., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The clinical utility of rapid multiplex respiratory specimen PCR panels for pneumonia for patients with suspected pneumonia is undefined. We aimed to compare the effect of the BioFire FilmArray pneumonia panel (bioMérieux, Salt Lake City, UT, USA) with standard of care testing on antibiotic use in a real-world hospital setting., Methods: We conducted a single-centre, open-label, pragmatic, randomised controlled trial at the Mayo Clinic, Rochester, MN, USA. Hospitalised patients (aged ≥18 years) with suspected pneumonia, from whom expectorated or induced sputum, tracheal secretions, or bronchoalveolar lavage fluid respiratory culture samples (one per individual) could be collected during index hospitalisation, were eligible for inclusion. Samples from eligible participants were randomly assigned (1:1) with a computerised tool to undergo testing with either the BioFire FilmArray pneumonia panel, conventional culture, and antimicrobial susceptibility testing (intervention group) or conventional culture and antimicrobial susceptibility testing alone (control group). Antimicrobial stewardship review in both groups involved an assessment and recommendations for antibiotic modifications based on clinical data and the results from the BioFire FilmArray pneumonia panel, conventional culture, or both. The primary outcome was median time to first antibiotic modification (ie, escalation or de-escalation of antibiotics against Gram-negative and Gram-positive bacteria) within 96 h of randomisation, assessed with the Wilcoxon rank-sum test and analysed in a modified intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT05937126)., Findings: Between Sept 15, 2020, and Sept 19, 2022, 1547 patients were screened for eligibility, of whom 1181 (76·3%) were randomly assigned: 582 (49·3%) to the intervention group and 599 (50·7%) to the control group. In total, 1152 participants were included in the modified intention-to-treat analysis, 589 (51·1%) in the control group and 563 (48·9%) in the intervention group. For the modified intention-to-treat population, median time to any first antibiotic modification was 20·4 h (95% CI 18·0-20·4) in the intervention group and 25·8 h (22·0-28·7) in the control group (p=0·076). Median time to any antibiotic escalation was 13·8 h (9·2-19·0) in the intervention group and 24·1 h (19·5-29·6) in the control group (p=0·0022). Median time to escalation of antibiotics against Gram-positive organisms was 10·3 h (6·2-30·9) in the intervention group and 24·6 h (19·5-37·2) in the control group (p=0·044); median time to escalation of antibiotics against Gram-negative organisms was 17·3 h (10·8-23·3) in the intervention group and 27·2 h (21·3-33·9) in the control group (p=0·010). Median time to any antibiotic de-escalation did not differ between groups (p=0·37). Median time to first de-escalation of antibiotics against Gram-positive organisms was 20·7 h (17·8-24·0) in the intervention group and 27·8 h (22·9-33·0) in the control group (p=0·015); median time to first de-escalation of antibiotics against Gram-negative organisms did not differ between groups (p=0·46)., Interpretation: Clinical use of the BioFire FilmArray pneumonia panel might lead to faster antibiotic escalations, including for Gram-negative or Gram-positive bacteria, and faster antibiotic de-escalations directed at Gram-positive bacteria. Additional research is needed regarding antimicrobial de-escalation, especially when antibiotics with broad Gram-negative spectrum are being used, by use of rapid diagnostics in patients with lower respiratory tract infection., Funding: bioMérieux., Competing Interests: Declaration of interests RP and AV received funding from bioMérieux for this study. AV also received funding from Moderna for advisory board participation in 2021. AV reports being an inventor for Mayo Clinic Travel App interaction with Smart Medical Kit and Medical Kit for Pilgrims. PV reports research funding from Cidara, Scynexis, and Ansun; and serves as a consultant for AbbVie and Scynexis (all fees paid to Mayo Clinic). PV reports honoraria from the Merck Manuals and Current Fungal Infection Reports. RP reports grants from ContraFect, TenNor Therapeutics, and bioMérieux. RP is a consultant to PHAST, Torus Biosystems, Day Zero Diagnostics, Mammoth Biosciences, and HealthTrackRx; monies are paid to Mayo Clinic. Mayo Clinic and RP have a relationship with Pathogenomix. RP has research supported by Adaptive Phage Therapeutics. Mayo Clinic has a royalty-bearing, know-how agreement and equity in Adaptive Phage Therapeutics. RP is also a consultant to Netflix, Abbott Laboratories, Oxford Nanopore Technologies, and CARB-X. RP has an issued patent on Bordetella pertussis–parapertussis PCR; a patent issued on a device for sonication, with royalties paid by Samsung to Mayo Clinic; and an issued patent on an anti-biofilm substance. RP receives honoraria from the National Board of Medical Examiners, Up-to-Date, and the Infectious Diseases Board Review Course. AJT receives honoraria from Up-To-Date. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background : Nocardia is an uncommon pathogen that has been reported to infect musculoskeletal structures. However, studies are largely limited to case reports, and little is known regarding management and outcomes of these infections. Methods : We performed a multicenter retrospective cohort study of adults with culture-confirmed musculoskeletal Nocardia infections at three Mayo Clinic centers in Arizona, Florida, and Minnesota from November 2011 through April 2022. Results : Nine cases of Nocardia musculoskeletal infection were identified. Seven (78 %) occurred in men, and the median age was 57.3 years (range 32.6-79.0). Specific infections included native joint septic arthritis with or without associated osteomyelitis ( N = 3 ), hardware-associated infection ( N = 1 ), sternal osteomyelitis ( N = 1 ), pyomyositis ( N = 2 ), bursitis ( N = 1 ), and tenosynovitis ( N = 1 ). Three cases (33 %) were associated with disseminated disease, all three occurring in solid organ transplant recipients. Surgical intervention was performed in all but the bursitis case. Length of treatment varied from 21 d for tenosynovitis to 467 d for osteomyelitis. The 1-year mortality was 22 %, and all fatal cases involved disseminated disease. Conclusion : Patients with localized nocardiosis affecting musculoskeletal structures generally have good outcomes, as opposed to those with disseminated infection. Management often required operative intervention, with one patient experiencing recurrence within 1 year., Competing Interests: The contact author has declared that none of the authors has any competing interests., (Copyright: © 2024 Ryan B. Khodadadi et al.)

Total joint arthroplasty (TJA) ranks among the most commonly performed orthopedic surgeries, with its annual incidence on the rise globally. Periprosthetic joint infection (PJI) remains a leading cause of arthroplasty failure. This review aims to summarize recent literature updates on the epidemiology, diagnosis, and management of PJI., Competing Interests: Disclosure The Authors have nothing to disclose. Declaration of AI and AI-assisted technologies in the writing process: During the preparation of this work, the authors used ChatGPT in order to check the grammar and improve readability. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Most data on irrigation and debridement with component retention (IDCR) as a treatment for acute periprosthetic joint infections (PJIs) focuses on primary total joint arthroplasties (TJAs). However, the incidence of PJI is greater after revisions. We investigated the outcomes of IDCR with suppressive antibiotic therapy (SAT) following aseptic revision TJAs., Methods: Through our total joint registry, we identified 45 aseptic revision TJAs (33 hips, 12 knees) performed from 2000 to 2017 that were treated with IDCR for acute PJI. Acute hematogenous PJI was present in 56%. Sixty-four percent of PJIs involved Staphylococcus. All patients were treated with 4 to 6 weeks of intravenous antibiotics with the intention to treat with SAT (89% received SAT). The mean age was 71 years (range, 41 to 90), with 49% being women and a mean body mass index of 30 (range, 16 to 60). The mean follow-up was 7 years (range, 2 to 15)., Results: The 5-year survivorships free from re-revision for infection and reoperation for infection were 80% and 70%, respectively. Of the 13 reoperations for infection, 46% involved the same species as the initial PJI. The 5-year survivorships free from any revision and any reoperation were 72% and 65%, respectively. The 5-year survivorship free from death was 65%., Conclusion: At 5 years following IDCR, 80% of implants were free from re-revision for infection. As the penalty for implant removal is often high in revision TJAs, IDCR with SAT is a viable option for acute infection after revision TJAs in select patients., Level of Evidence: IV., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Recent evidence has suggested a benefit to extended postoperative prophylactic oral antibiotics after two-stage exchange arthroplasty for treatment of periprosthetic joint infections. We sought to determine reinfection rates with and without a short course of oral antibiotics after two-stage exchange procedures., Methods: A retrospective review identified patients undergoing two-stage exchange arthroplasty for periprosthetic joint infection of the hip or knee. Patients were excluded if they failed a prior two-stage exchange, had positive cultures at reimplantation, prolonged intravenous antibiotics postoperatively, and/or life-long suppression. This resulted in 444 reimplantations (210 hips and 234 knees). Patients were divided into three cohorts based on the duration of oral antibiotics after reimplantation: no antibiotics (102), ≤2 weeks (266), or >2 weeks (76). The primary endpoint was reinfection within 1 year of reimplantation., Results: Within 1 year of reimplantation, there were 34 reinfections. In the no-antibiotic, ≤ 2-week, and >2-week cohorts the reinfection rates were 14.1, 7.0, and 6.4%, respectively. Multivariate Cox regression showed a reduced reinfection rate in the ≤2-week cohort relative to no antibiotics (hazard ratio [HR]: 0.38, P = .01). While the smaller cohort with >2 weeks of antibiotics did not significantly reduce the reinfection rate (HR: 0.41, P = .12), when combined with the ≤2-week cohort, use of oral antibiotics had an overall reduction of the reinfection rate (HR: 0.39, P = .01)., Conclusions: These data support the hypothesis that a short course of oral antibiotics after reimplantation decreases the 1-year reinfection rate. Future randomized studies should seek to examine the efficacy of different durations of oral antibiotics to reduce reinfection., Level of Evidence: Prognostic Level IV., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective : confluent T1 hypointense marrow signal is widely accepted to represent osteomyelitis on MRI. Some authors have suggested that non-confluent bone marrow signal abnormality should be considered early osteomyelitis. The purpose of this study was to address this issue by comparing the rate of osteomyelitis and amputation based on T1 marrow signal characteristics. Materials and methods : a total of 112 patients who underwent MRI of the foot for the evaluation of possible osteomyelitis were included. Patients were assigned to confluent T1 hypointense, reticulated T1 hypointense, and normal bone marrow signal groups. Results : patients with confluent T1 hypointense signal on MRI had significantly higher rates of osteomyelitis and amputation at 2 and 14 months post-MRI than the reticulated T1 hypointense group ( p < 0.001 ). Six patients had normal T1 signal, 16.7 % of whom had osteomyelitis and underwent amputation by 2 months post-MRI. Of 61 patients with reticulated T1 hypointense signal, 19.7 % had a diagnosis of osteomyelitis at 2 months post-MRI and 30.8 % had a diagnosis of osteomyelitis at 14 months post-MRI; moreover, 14.8 % and 31.5 % underwent amputation by 2 and 14 months post-MRI, respectively. Of 45 patients with confluent T1 hypointense signal, 73.3 % of patients had osteomyelitis at 2 months post-MRI and 82.5 % had osteomyelitis at 14 months post-MRI. In this group, 66.7 % underwent amputation by 2 months post-MRI and 77.8 % underwent amputation by 14 months post-MRI. Conclusions : over half of the patients with suspected pedal osteomyelitis who had reticulated or normal T1 bone marrow signal on MRI healed with conservative measures. Therefore, we recommend terminology such as "osteitis", "reactive osteitis", or "nonspecific reactive change" to describe bone marrow edema-like signal and reticulated hazy T1 hypointense signal without associated confluent T1 hypointensity. Moreover, we recommend that the MRI diagnosis of osteomyelitis is reserved for confluent T1 hypointense bone signal in the area of concern., Competing Interests: The contact author has declared that none of the authors has any competing interests., (Copyright: © 2023 Christin A. Tiegs-Heiden et al.)

Background: Extended oral antibiotic prophylaxis (EOA) has been shown to reduce infection after high-risk primary total hip arthroplasties (THAs) and reimplantations. However, data are limited regarding EOA after aseptic revision THAs. This study evaluated the impact of EOA on infection-related outcomes after aseptic revision THAs., Methods: We retrospectively identified 1,107 aseptic revision THAs performed between 2014 and 2019. Patients who received EOA >24 hours perioperatively (n = 370) were compared to those who did not (n = 737) using an inverse probability of treatment weighting model. Their mean age was 65 years (range, 19-98 years), mean body mass index was 30 kg/m 2 (range, 16-72), and 54% were women. Outcomes included cumulative probabilities of any infection, periprosthetic joint infection (PJI), and re-revision or reoperation for infection. Mean follow-up was 4 years (range, 2-8 years)., Results: The cumulative probability of any infection after aseptic revision THA was 2.3% at 90 days, 2.7% at 1 year, and 3.5% at 5 years. The cumulative probability of PJI was 1.7% at 90 days, 2.1% at 1 year, and 2.8% at 5 years. There was a trend toward an increased risk of any infection (hazards ratio [HR] = 2.6; P = .058), PJI (HR = 2.6; P = .085), and re-revision (HR = 6.5; P = .077) or reoperation (HR = 2.3; P = .095) for infection in patients who did not have EOA at the final clinical follow-up., Conclusions: EOA after aseptic revision THA was not associated with a statistically significant decreased risk of any infection, PJI, or re-revision or reoperation for infection at all time points., Level of Evidence: Level III., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Extended oral antibiotic prophylaxis (EOA) has been shown to potentially reduce infection rates after high-risk primary total knee arthroplasties (TKAs) and reimplantations. However, data is limited regarding EOA after aseptic revision TKAs. This study evaluated the impact of EOA on infection-related outcomes after aseptic revision TKAs., Methods: 904 aseptic revision TKAs from 2014-2019 were retrospectively identified. Patients who received EOA >24 hours perioperatively (n = 267) were compared to those who did not (n = 637) using an inverse probability of treatment weighting model. Mean age was 66 years, mean BMI was 33 kg/m 2 , and 54% were female. Outcomes included cumulative probabilities of any infection, periprosthetic joint infection (PJI), superficial infection, and re-revision or reoperation for infection., Results: The cumulative probability of any infection after aseptic revision TKA was 1.9% at 90 days, 3.5% at 1 year, and 8.1% at 5 years. Patients without EOA had a higher risk of any infection at 90 days (HR = 7.1; P = .01), but not other time points. The cumulative probability of PJI after aseptic revision TKA was 0.8% at 90 days, 2.3% at 1 year, and 6.5% at 5 years. Patients without EOA did not have an increased risk of PJI. There were no differences in re-revision or reoperation for infection at any time point between groups., Conclusion: Extended oral antibiotics after aseptic revision TKA were associated with a 7-fold decreased risk of any infection at 90 days. The results suggest a potential role for EOA after aseptic revision TKA and warrant additional prospective studies., Level of Evidence: Level III., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Accurately detecting early postoperative periprosthetic joint infection (PJI) following total hip arthroplasty (THA) and total knee arthroplasty (TKA) remains challenging. The purpose of our study was to determine the impact of antibiotics given prior to laboratory evaluation on the reliability of serologic and synovial fluid tests to identify PJI in the early postoperative period., Methods: We identified 49,861 primary total hip arthroplasties and total knee arthroplasties performed between 2000 and 2019. Among these patients, 21 hips and 28 knees that underwent arthrocentesis within 12 weeks of their arthroplasty were identified as infected. Patients who had received antibiotics within 2 weeks prior to laboratory evaluation were compared to those who had not. Median values of C-reactive protein, erythrocyte sedimentation rate, synovial white blood cell (WBC) count, synovial neutrophil percentage, and synovial absolute neutrophil count were compared between groups. The false negative rate for detecting PJI using laboratory values was compared using published cutoffs for PJI in the early postoperative period., Results: Median values of C-reactive protein (105 vs 22 mg/L; P = .006), synovial WBC count (57,591 vs 4,473 cells/μL; P = .003), synovial neutrophil percentage (94% vs 76%; P = .004), and synovial absolute neutrophil count (50,748 vs 2,804 cells/μL; P < .001) were significantly lower in patients who received antibiotics compared to those who did not. False negative rates for detecting PJI were significantly higher for synovial WBC and synovial neutrophil percentage in patients treated with antibiotics compared to untreated patients., Conclusion: False negative rates for detecting early PJI when using published cutoffs were markedly higher in antibiotic-treated patients compared to untreated patients for synovial WBC count and synovial neutrophil percentage., Level of Evidence: Level IV retrospective review., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Diagnosing early periprosthetic joint infection (PJI) after primary total hip arthroplasty (THA) remains challenging. We sought to validate optimal laboratory value cutoffs for detecting early PJIs in a series of primary THAs from one institution., Methods: We retrospectively identified 22,795 primary THAs performed between 2000 and 2019. Within 12 weeks, 43 hips (43 patients) underwent arthrocentesis. Patients were divided into 2 groups: evaluation ≤6 weeks or 6-12 weeks following THA. The 2011 Musculoskeletal Infection Society major criteria for PJI diagnosed PJI in 15 patients. Mann-Whitney U-tests were used to compare median laboratory values and receiver operating characteristic curve analysis was used to evaluate optimal cutoff values., Results: Both within 6 weeks and between 6 and 12 weeks postoperatively, median C-reactive protein (CRP), erythrocyte sedimentation rate, synovial white blood cell (WBC) count, neutrophil percentage, and absolute neutrophil count (ANC) values were significantly higher in infected THAs. Optimal cutoffs within 6 weeks were: CRP ≥100 mg/L, synovial WBCs ≥4390 cells/μL, neutrophil percentage ≥74%, and ANC ≥3249 cells/μL. Between 6 and 12 weeks, optimal cutoffs were: CRP ≥33 mg/L, synovial WBCs ≥26,995 cells/μL, neutrophil percentage ≥93%, and ANC ≥25,645 cells/μL., Conclusion: Early PJI following THA should be suspected within 6 weeks with CRP ≥100 mg/L or synovial WBCs ≥4390 cells/μL. Between 6 and 12 weeks postoperatively, cutoffs of CRP ≥33 mg/L, synovial fluid WBC ≥26,995 cells/μL, and neutrophil percentage ≥93% diagnosed PJI with high accuracy., Level of Evidence: Level IV Diagnostic., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: Septic arthritis of the hip often leads to irreversible osteoarthritis (OA) and the requirement for total hip arthroplasty (THA). The aim of this study was to report the mid-term risk of any infection, periprosthetic joint infection (PJI), aseptic revision, and reoperation in patients with a past history of septic arthritis who underwent THA, compared with a control group of patients who underwent THA for OA., Methods: We retrospectively identified 256 THAs in 244 patients following septic arthritis of the native hip, which were undertaken between 1969 and 2016 at a single institution. Each case was matched 1:1, based on age, sex, BMI, and year of surgery, to a primary THA performed for OA. The mean age and BMI were 58 years (35 to 84) and 31 kg/m 2 (18 to 48), respectively, and 100 (39%) were female. The mean follow-up was 11 years (2 to 39)., Results: The ten-year survival free of any infection was 91% and 99% in the septic arthritis and OA groups, respectively (hazard ratio (HR) = 13; p < 0.001). The survival free of PJI at ten years was 93% and 99% in the septic arthritis and OA groups, respectively (HR = 10; p = 0.002). There was a significantly higher rate of any infection at ten years when THA was undertaken within five years of the diagnosis of septic arthritis compared with those in whom THA was undertaken > five years after this diagnosis was made (14% vs 5%, respectively; HR = 3.1; p = 0.009), but there was no significant difference in ten-year survival free of aseptic revision (HR = 1.14; p = 0.485). The mean Harris Hip Scores at two and five years postoperatively were significantly lower in the septic arthritis group compared with the OA group (p = 0.001 for both)., Conclusion: There was a ten-fold increased risk of PJI in patients with a history of septic arthritis who underwent THA compared with those who underwent THA for OA with a ten-year cumulative incidence of 7%. The risk of any infection had a strong downward trend as the time interval between the diagnosis of septic arthritis and THA increased, highlighted by a 3.1-fold higher risk when THAs were performed within five years of the diagnosis being made. Cite this article: Bone Joint J  2022;104-B(2):227-234.

Background: Septic arthritis of the native knee often results in irreversible joint damage leading to the need for total knee arthroplasty (TKA). The purpose of the present study was to examine the intermediate-term risk of periprosthetic joint infection (PJI), aseptic revision, and reoperation following primary TKA in patients with a history of septic arthritis of the native knee as compared with primary TKA performed for the treatment of osteoarthritis., Methods: We retrospectively identified 215 primary TKAs performed from 1971 to 2016 at a single institution in patients with a history of septic arthritis of the native knee. Each case was matched 1:1 based on age, sex, body mass index (BMI), and surgical year to a TKA for osteoarthritis. The mean age and BMI were 63 years and 30 kg/m2, respectively. The mean duration of follow-up was 9 years., Results: Survivorships free of PJI at 10 years were 90% and 99% for the septic arthritis and osteoarthritis groups, respectively (hazard ratio [HR] = 6.1; p < 0.01). Ten-year survivorships free of any aseptic revisions were 83% and 93% (HR = 2.5; p < 0.01), and survivorships free of any reoperation were 61% and 84% (HR = 2.9; p < 0.01) for the septic arthritis and osteoarthritis groups, respectively. In addition, as time from the diagnosis of native knee septic arthritis to TKA increased, the relative risk of subsequent infection decreased. Preoperative and 2-year postoperative Knee Society scores were similar between the groups (p = 0.16 and p = 0.19, respectively)., Conclusions: There was a 6.1-fold increased risk of PJI in patients undergoing TKA with a history of native knee septic arthritis when compared with controls undergoing TKA for the treatment of osteoarthritis, with a cumulative incidence of 9% at 10 years. Subgroup analysis of the septic arthritis cohort revealed a higher risk of any infection in patients who underwent TKA within the first 5 to 7 years after the diagnosis of septic arthritis as compared with those with a greater duration. Moreover, the 10-year rates of survival free of aseptic revision, any revision, and any reoperation were significantly worse in the native knee septic arthritis cohort., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/G605)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Fluoroquinolones (FQs) are known to be accompanied by significant risks. However, the incidence of adverse events (ADEs) resulting in unplanned drug discontinuation when used for periprosthetic joint infections (PJIs) is currently unknown., Methods: This study included 156 patients over the age of 18 treated for staphylococcal PJI with debridement, antibiotics, and implant retention between 1 January 2007 and 21 November 2019. Of the 156 patients, 64 had total hip arthroplasty (THA) and 92 had total knee arthroplasty (TKA) infections. The primary outcome was rate of unplanned drug discontinuation. Secondary outcomes included incidence of severe ADEs, unplanned rifamycin discontinuation, mean time to unplanned regimen discontinuation, and all-cause mortality., Results: Overall, unplanned drug discontinuation occurred in 35.6% of patients in the FQ group and 3% of patients in the non-FQ group. The rate of unplanned discontinuation of FQ regimens as compared with non-FQ regimens was 27.5% vs 4.2% (P = .021) in THA infections and 42% vs 2.4% (P < .001) in TKA infections. There was no significant difference in severe ADEs between FQ and non-FQ regimens in both THA and TKA infections. The overall rate of nonsevere ADEs in FQ compared with non-FQ regimens was 43.3% vs 6.1% (P < .001). FQs were associated with tendinopathy, myalgia, arthralgia, and nausea., Conclusions: A significantly higher rate of unplanned drug discontinuation was associated with FQ as compared with non-FQ regimens. This provides a real-world view of the implications of FQ-related ADEs on unplanned discontinuation when used in prolonged durations for the management of staphylococcal PJIs., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

After staphylococci, streptococci and enterococci are the most frequent causes of periprosthetic joint infection (PJI). MICs and minimum biofilm bactericidal concentrations of rifampin, rifabutin, and rifapentine were determined for 67 enterococcal and 59 streptococcal PJI isolates. Eighty-eight isolates had rifampin MICs of ≤1 μg/ml, among which rifabutin and rifapentine MICs were ≤ 8 and ≤4 μg/ml, respectively. There was low rifamycin in vitro antibiofilm activity except for a subset of Streptococcus mitis group isolates. IMPORTANCE Rifampin is an antibiotic with antistaphylococcal biofilm activity used in the management of staphylococcal periprosthetic joint infection with irrigation and debridement with component retention; some patients are unable to receive rifampin due to drug interactions or intolerance. We recently showed rifabutin and rifapentine to have in vitro activity against planktonic and biofilm states of rifampin-susceptible periprosthetic joint infection-associated staphylococci. After staphylococci, streptococci and enterococci combined are the most common causes of periprosthetic joint infection. Here, we investigated the in vitro antibiofilm activity of rifampin, rifabutin, and rifapentine against 126 Streptococcus and Enterococcus periprosthetic joint infection isolates. In contrast to our prior findings with staphylococcal biofilms, there was low antibiofilm activity of rifampin, rifabutin, and rifapentine against PJI-associated streptococci and enterococci, apart from some Streptococcus mitis group isolates.

Background: Two-stage exchange arthroplasty with high-dose antibiotic-loaded bone cement spacer and intravenous (IV) antibiotics is the most common method of managing infected total hip arthroplasties. However, the contemporary incidence, risk factors, and outcomes of acute kidney injuries (AKIs) in this cohort are unknown., Methods: We identified 227 patients treated with 256 antibiotic-loaded bone cement spacers after resection of an infected primary total hip arthroplasty between 2000 and 2017. Mean age was 65 years, mean body mass index was 30 mg/kg 2 , 55% were men, and 16% had pre-existing chronic kidney disease (CKD). Spacers were in situ for a mean of 15 weeks, concomitantly associated with IV or oral antibiotics for a mean of 6 weeks. AKI was defined as a creatinine ≥1.5X baseline or ≥0.3 mg/dL. Mean follow-up was 8 years., Results: AKI occurred in 13 patients without pre-existing CKD (7%) vs 10 patients with CKD (28%; OR 5; P = .0001). None required acute dialysis. Postoperative fluid depletion (β = 0.31; P = .0001), ICU requirement (β = 0.40; P = .0001), and acute atrial fibrillation (β = 0.43; P = .0001) were independent predictors for AKI in patients without pre-existing CKD. Duration of in situ spacer, mean antibiotic dose in cement, use of amphotericin B, and type of IV antibiotics were not significant risk factors. At last follow-up, 8 AKIs progressed to CKD, with one receiving dialysis 7 years later., Conclusion: AKIs occurred in 7% of patients with normal renal function, with 5-fold greater risk in those with CKD, and 4% did develop CKD. Importantly, causes of acute renal blood flow impairment were independent predictors for AKI., Level of Evidence: Level III, comparative study., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: It remains difficult to diagnose early postoperative periprosthetic joint infection (PJI) following total knee arthroplasty (TKA). We aimed to validate the optimal cutoff values of ESR, CRP, and synovial fluid analysis for detecting early postoperative PJI in a large series of primary TKAs., Methods: We retrospectively identified 27,066 primary TKAs performed between 2000 and 2019. Within 12 weeks, 169 patients (170 TKAs) had an aspiration. The patients were divided into two groups: those evaluated ≤ six weeks, or between six and 12 weeks postoperatively. The 2011 Musculoskeletal Infection Society (MSIS) criteria for PJI diagnosis in 22 TKAs. The mean follow-up was five years (two months to 17 years). The results were compared using medians and Mann-Whitney U tests and thresholds were analyzed using receiver operator characteristic curves., Results: Within six weeks, the median CRP (101 mg/l vs 35 mg/l; p = 0.011), synovial WBCs (58,295 cells/μl vs 2,121 cells/μl; p ≤ 0.001), percentage of synovial neutrophils (91% vs 71% (p < 0.001), and absolute synovial neutrophil count (ANC) (50,748 cells/μl vs 1,386 cells/μl (p < 0.001) were significantly higher in infected TKAs. Between six and 12 weeks, the median CRP (85 mg/l vs 5 mg/l (p < 0.001)), ESR (33 mm/hr vs 14 mm/hr (p = 0.015)), synovial WBCs (62,247 cells/μl vs 620 cells/μl (p < 0.001)), percentage of synovial neutrophils (93% vs 54% (p < 0.001)), and ANC (55,911 cells/μl vs 326 cells/μl (p < 0.001)) were also significantly higher in infected TKAs. Optimal thresholds at ≤ six weeks were: CRP ≥ 82 mg/l (sensitivity 70%, specificity 77%), synovial WBCs ≥ 8,676 cells/μl (83%, 90%), percentage of synovial neutrophils ≥ 88% (67%, 78%), and ANC ≥ 8,346 cells/μl (83%, 91%). Between six and 12 weeks, thresholds were: CRP ≥ 34 mg/l (90%, 93%), synovial WBCs ≥ 1,983 cells/μl (80%, 85%), percentage of synovial neutrophils ≥ 76% (80%, 81%), and ANC ≥ 1,684 cells/μl (80%, 87%)., Conclusion: Early PJI after TKA should be suspected within six weeks if the CRP is ≥ 82 mg/l, synovial WBCs are ≥ 8,676 cells/μl, the percentage of synovial neutrophils is ≥ 88%, and/or the ANC is ≥ 8,346 cells/μl. Between six and 12 weeks, thresholds include a CRP of ≥ 34 mg/l, synovial WBC of ≥ 1,983 cells/μl, a percentage of synovial neutrophils of ≥ 76%, and/or an ANC of ≥ 1,684 cells/μl. Cite this article: Bone Joint J  2021;103-B(6 Supple A):177-184.

Aims: The aim of this study was to determine the diagnostic accuracy of α defensin (AD) lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) tests for periprosthetic joint infection (PJI) in comparison to conventional synovial white blood cell (WBC) count and polymorphonuclear neutrophil percentage (PMN%) analysis., Methods: Patients undergoing joint aspiration for evaluation of pain after total knee arthroplasty (TKA) or total hip arthroplasty (THA) were considered for inclusion. Synovial fluids from 99 patients (25 THA and 74 TKA) were analyzed by WBC count and PMN% analysis, AD LFA, and AD ELISA. WBC and PMN% cutoffs of ≥ 1,700 cells/mm 3 and ≥ 65% for TKA and ≥ 3,000 cells/mm 3 and ≥ 80% for THA were used, respectively. A panel of three physicians, all with expertise in orthopaedic infections and who were blinded to the results of AD tests, independently reviewed patient data to diagnose subjects as with or without PJI. Consensus PJI classification was used as the reference standard to evaluate test performances. Results were compared using McNemar's test and area under the receiver operating characteristic curve (AUC) analysis., Results: Expert consensus classified 18 arthroplasies as having failed due to PJI and 81 due to aseptic failure. Using these classifications, the calculated sensitivity and specificity of AD LFA was 83.3% (95% confidence interval (CI) 58.6 to 96.4) and 93.8% (95% CI 86.2 to 98.0), respectively. Sensitivity and specificity of AD ELISA was 83.3% (95% CI 58.6 to 96.4) and 96.3% (95% CI 89.6 to 99.2), respectively. There was no statistically significant difference between sensitivity (p = 1.000) or specificity (p = 0.157) of the two AD assays. AUC for AD LFA was 0.891. In comparison, AUC for synovial WBC count, PMN%, and the combination of the two values was 0.821 (sensitivity p = 1.000, specificity p < 0.001), 0.886 (sensitivity p = 0.317, specificity p = 0.011), and 0.926 (sensitivity p = 0.317, specificity p = 0.317), respectively., Conclusion: The diagnostic accuracy of synovial AD for PJI diagnosis is comparable and not statistically superior to that of synovial WBC count plus PMN% combined. Cite this article: Bone Joint J  2021;103-B(6):1119-1126.

Background: Two-stage exchange arthroplasty with a high-dose antibiotic-loaded bone cement (ALBC) spacer and intravenous or oral antibiotics is the most common method of managing a periprosthetic joint infection (PJI) after a total knee arthroplasty (TKA). However, little is known about the contemporary incidence, the risk factors, and the outcomes of acute kidney injuries (AKIs) in this cohort., Methods: We identified 424 patients who had been treated with 455 ALBC spacers after resection of a PJI following a primary TKA from 2000 to 2017. The mean age at resection was 67 years, the mean body mass index (BMI) was 33 kg/m2, 47% of the patients were women, and 15% had preexisting chronic kidney disease (CKD). The spacers (87% nonarticulating) contained a mean of 8 g of vancomycin and 9 g of an aminoglycoside per construct (in situ for a mean of 11 weeks). Eighty-six spacers also had amphotericin B (mean, 412 mg). All of the patients were concomitantly treated with systemic antibiotics for a mean of 6 weeks. An AKI was defined as a creatinine level of ≥1.5 times the baseline or an increase of ≥0.3 mg/dL within any 48-hour period. The mean follow-up was 6 years (range, 2 to 17 years)., Results: Fifty-four AKIs occurred in 52 (14%) of the 359 patients without preexisting CKD versus 32 AKIs in 29 (45%) of the 65 patients with CKD (odds ratio [OR], 5; p = 0.0001); none required acute dialysis. Overall, when the vancomycin concentration or aminoglycoside concentration was >3.6 g/batch of cement, the risk of AKI increased (OR, 1.9 and 1.8, respectively; p = 0.02 for both). Hypertension (β = 0.17; p = 0.002), perioperative hypovolemia (β = 0.28; p = 0.0001), and acute atrial fibrillation (β = 0.13; p = 0.009) were independent predictors for AKI in patients without preexisting CKD. At the last follow-up, 8 patients who had sustained an AKI had progressed to CKD, 4 of whom received dialysis., Conclusions: In our study, the largest series to date that we are aware of regarding this issue, AKI occurred in 14% of patients with normal renal function at baseline, and 2% developed CKD after undergoing a 2-stage exchange arthroplasty for a PJI after TKA. However, the risk of AKI was fivefold greater in those with preexisting CKD. The causes of acute renal blood flow impairment were independent predictors for AKI., Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The authors indicated that no external funding was received for any aspect of this work. On the Disclosure of Potential Conflicts of Interest forms, which are provided with the online version of the article, one or more of the authors checked “yes” to indicate that the author had a relevant financial relationship in the biomedical arena outside the submitted work; “yes” to indicate that the author had a patent and/or copyright, planned, pending, or issued, broadly relevant to this work; and “yes” to indicate that the author had other relationships or activities that could be perceived to influence, or have the potential to influence, what was written in this work (http://links.lww.com/JBJS/G370)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

High-dose liquid antibiotics are uncommon in bone cement. We present a case series of patients in which up to 16 mL of liquid amikacin (250 mg mL - 1 ) was successfully incorporated into bone cement to treat periprosthetic joint infections. We did not observe adverse drug reactions definitively attributed to its use., Competing Interests: Don Bambino Geno Tai, Nathan J. Brinkman, Omar Abu Saleh, Christina G. Rivera, Douglas R. Osmon declare that they have no conflict of interest. Matthew P. Abdel receives royalties from Stryker and Springer. He is a member of the American Academy of Orthopedic Surgeons' board of directors., (Copyright: © 2021 Don Bambino Geno Tai et al.)

Cefazolin is commonly used as an alternative to antistaphylococcal penicillins (ASPs) in treating methicillin-susceptible Staphylococcus aureus (MSSA) infections; however, no study has compared these agents in MSSA spinal epidural abscess (SEA). We describe our experience in managing MSSA SEA and compare the clinical efficacy of cefazolin with ASPs. This retrospective multicenter study reviewed 79 adult patients diagnosed with SEA between January 2006 and July 2020 using data collected from electronic health records and clinical microbiology laboratory databases. Forty-five patients received cefazolin, while 34 received ASPs. The total antibiotic duration was longer in the ASPs group but not statistically significant. There were no significant differences in treatment failure at week 6 vs week 12, 30-day vs overall mortality, or in 90-day recurrence rates between the treatment groups. Cefazolin was equally as effective as ASPs, and our findings suggest that it can be an alternative to ASPs in the treatment of MSSA SEA., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Periprosthetic joint infection (PJI) data elements are contained in both structured and unstructured documents in electronic health records and require manual data collection. The goal of this study is to develop a natural language processing (NLP) algorithm to replicate manual chart review for PJI data elements., Methods: PJI was identified among all total joint arthroplasty (TJA) procedures performed at a single academic institution between 2000 and 2017. Data elements that comprise the Musculoskeletal Infection Society (MSIS) criteria were manually extracted and used as the gold standard for validation. A training sample of 1208 TJA surgeries (170 PJI cases) was randomly selected to develop the prototype NLP algorithms and an additional 1179 surgeries (150 PJI cases) were randomly selected as the test sample. The algorithms were applied to all consultation notes, operative notes, pathology reports, and microbiology reports to predict the correct status of PJI based on MSIS criteria., Results: The algorithm, which identified patients with PJI based on MSIS criteria, achieved an f1-score (harmonic mean of precision and recall) of 0.911. Algorithm performance in extracting the presence of sinus tract, purulence, pathologic documentation of inflammation, and growth of cultured organisms from the involved TJA achieved f1-scores that ranged from 0.771 to 0.982, sensitivity that ranged from 0.730 to 1.000, and specificity that ranged from 0.947 to 1.000., Conclusion: NLP-enabled algorithms have the potential to automate data collection for PJI diagnostic elements, which could directly improve patient care and augment cohort surveillance and research efforts. Further validation is needed in other hospital settings., Level of Evidence: Level III, Diagnostic., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Despite the high rate of success of primary total knee arthroplasty (TKA), some patients are candidates for early aseptic reoperation. The goal of this study is to evaluate the risk of subsequent periprosthetic joint infection (PJI) in patients treated with an aseptic reoperation within 1 year of primary TKA., Methods: A retrospective review of our total joint registry compared 249 primary TKAs requiring an aseptic reoperation within 1 year following index arthroplasty to a control group of 17,867 TKAs not requiring reoperation within 1 year. Patients were divided into groups based on time from index TKA: (1) 90 days or less (114 TKAs) and (2) 91 to 365 days (135 TKAs). Mean age was 68 years with 57% female. Mean follow-up was 7 years., Results: At 2 years postoperatively, patients undergoing an aseptic reoperation within 90 days subsequently had a 9% PJI rate, while patients undergoing an aseptic reoperation between 91 and 365 days subsequently had a 3% PJI rate. The control group had a 0.4% PJI rate. Compared to the control group, patients undergoing an aseptic reoperation within 90 days had an elevated risk of PJI (hazard ratio, 9; P < .0001), as did patients who had a reoperation between 91 and 365 days (hazard ratio, 4; P < .0001)., Conclusion: Aseptic reoperation within 1 year of primary TKA was associated with a notably increased risk of subsequent PJI., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Owing to patient intolerance or drug interactions, alternative agents to rifampin are needed for management of staphylococcal periprosthetic joint infection. In the current study, we evaluated rifabutin, rifapentine and rifampin, with and without vancomycin, in a rat model of foreign body osteomyelitis., Methods: Proximal tibiae were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and a Kirschner wire (K-wire) implanted in each. After 4 weeks of infection, rifampin, rifabutin, or rifapentine were administered, alone or with vancomycin. Tibiae and K-wires were cultured, and medians were reported as log10 colony-forming units (CFUs) per gram of bone or log10 CFUs per K-wire, respectively., Results: Rifampin, rifabutin or rifapentine administered with vancomycin yielded less MRSA from bones (0.10, 3.02, and 0.10 log10 CFUs/g, respectively) than did no treatment (4.36 log10 CFUs/g) or vancomycin alone (4.64 log10 CFUs/g) (both P ≤ .02). The K-wires of animals receiving no treatment or vancomycin monotherapy recovered medians of 1.76 and 2.91 log10 CFUs/g per K-wire, respectively. In contrast, rifampin, rifabutin and rifapentine administered with vancomycin yielded medians of 0.1 log10 CFUs per K-wire, respectively. Rifampin resistance was detected in a single animal in the rifampin monotherapy group., Conclusions: Rifabutin or rifapentine with vancomycin were as active as rifampin with vancomycin against MRSA in rat foreign body osteomyelitis, suggesting that rifabutin and/or rifapentine may be alternatives to rifampin in the clinical management of staphylococcal periprosthetic joint infections., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: There are little data on the outcomes of primary total hip arthroplasties (THAs) in patients with a prior surgically treated hip or knee periprosthetic joint injection (PJI). The goal of this study was to compare the risk of infection in this population with matched controls., Methods: We retrospectively reviewed 48 patients whom underwent 50 primary THAs from 2000 to 2014 with a history of a PJI in a total knee arthroplasty or contralateral THA. Thirteen patients (27%) were on chronic antibiotic suppression at the time of primary THA. Mean age was 67 years, and mean body mass index was 35 kg/m 2 . Mean follow-up was 6 years. We 1:3 matched (age, sex, body mass index, cemented vs cementless femoral fixation, and surgical year) these cases to 150 primary THAs. Competing risk analysis, with death as the competing risk, was performed., Results: The cumulative incidence of PJI with death as a competing risk was 1.5-fold higher in the study cohort (2.0%) compared with matched controls (1.4%) (hazards ratio, 1.5; P = .75). The cumulative incidence of any infection with death as a competing risk was 2-fold higher in the study cohort (4.0%) compared with matched controls (2.1%) (hazards ratio, 2.0; P = .45). However, these were both statistically similar given the relatively small cohort. The overall complication rate, including infections and reoperations, was 17% in the study cohort., Conclusion: Patients undergoing a clean primary THA with a history of a total knee arthroplasty or contralateral THA PJI in another joint have a 2% and 4% risk of PJI and any infection, respectively. Moreover, nearly 1 in 5 patients experience at least 1 complication., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Despite the success of primary total hip arthroplasties (THAs), some patients will require an aseptic reoperation within 1 year of the index THA. The goal of this study is to evaluate the risk of subsequent periprosthetic joint infection (PJI) in patients undergoing an aseptic reoperation within 1 year of a primary THA., Methods: A retrospective review utilizing our institutional joint registry identified 211 primary THAs requiring aseptic reoperation within 1 year following index arthroplasty. A control group of 15,357 primary THAs not requiring reoperation within 1 year was identified. Patients were divided into groups based on time from primary THA to reoperation: (1) within 90 days (n = 112 THAs; 40% for dislocation, 34% for periprosthetic fracture) or (2) 91-365 days (n = 99 THAs; 37% for dislocation, 29% for periprosthetic fracture). Mean follow-up was 7 years., Results: Patients undergoing an aseptic reoperation within 90 days had a PJI rate of 4.8% at 2 years, while the 91-365 day group had a PJI rate of 3.2% at 2 years. The control group had a PJI rate of 0.2% at 2 years. Employing a multivariate analysis, reoperation within 90 days of index arthroplasty had an elevated risk of PJI (hazard ratio 8, P < .001) as did a reoperation between 91 and 365 days (hazard ratio 13, P < .001)., Conclusion: Aseptic reoperations within 1 year following primary THA resulted in an 8- to 13-fold increased risk of subsequent PJI. The risk was similar whether the aseptic reoperation was early (within 90 days) or later (91-365 days)., Level of Evidence: Level III (Prognostic)., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background : Fungal prosthetic joint infections (PJIs) are rare and often associated with poor outcome; however, risk factors are not well described. Methods : This was a retrospective case control study among all patients with PJIs from 2006-2016 at two major academic centers. Each fungal PJI case was matched 1:1 with a bacterial PJI control by joint (hip, knee, shoulder) and year of diagnosis. We compared demographics, comorbidities, and clinical characteristics between cases and controls using chi square/Fisher's exact or Wilcoxon rank sum test. Independent risk factors were identified with multivariable logistic regression. Results : Forty-one fungal PJIs occurred over the study and 61% were due to Candida albicans . The hip was involved in 51.2% of cases, followed by the knee (46.3%). Compared to bacterial PJI, fungal PJI cases were more likely to have received antibiotics within the previous 3 months (70.7% vs 34%, P =.001), wound drainage lasting >5 days (48% vs 9%, P =.0002), had a lower median CRP (2.95 mg/dl vs 5.99, P =.013) and synovial fluid white blood cell count (13,953 cells/mm 3 vs 33,198, P =.007), and a higher proportion of prior two-stage exchanges (82.9% vs 53.6%, P =.008). After controlling for center, prolonged wound drainage (OR, 7.3; 95% CI, 2.02-26.95) and recent antibiotics (OR, 3.4; 95% CI, 1.2-9.3) were significantly associated with fungal PJI. Conclusion : In our study, Candida albicans was the most common species in fungal PJIs and prolonged wound drainage and recent antibiotics were independent risk factors. These clinical characteristics may help providers anticipate fungal PJI and adjust management strategies., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Introduction: Prosthetic joint infection (PJI) due to Streptococcus bovis group (SBG), specifically S. bovis biotype I ( S. gallolyticus ), is rare and associated with colorectal carcinoma. Little has been published regarding SBG PJI. We analyzed nine cases of SBG PJI at our institution, the largest series to date. Methods : The medical records of patients diagnosed with SBG PJI between 2000-2017 were reviewed. Patients were followed until death, failure, or loss to follow-up. Mean follow-up was 37 months (range 0.5-74 months). Results: Nine PJI in 8 patients with mean prosthesis age at diagnosis of 8 years (range 4 weeks-17 years) were identified. The median duration between symptom onset and treatment was 38 weeks (range 0.3 weeks-175 weeks). 8/9 had their PJI eradicated with treatment based on acuity of symptoms. Acute PJI (2) was treated with DAIR, and chronic PJI (7) was treated with 2-stage revision arthroplasty. 1 PJI with chronic PJI developed recurrent infection after initial treatment. All patients received post-operative IV antibiotics. 7/8 patients received Ceftriaxone. Three patients received lifelong oral antibiotics. 7/8 patients underwent colonoscopy. 5/7 patients were found to have polyps following PJI diagnosis with one carcinoma and two dysplastic polyps. The two patients without polyps had identifiable gastrointestinal (GI) mucosal abnormality: tooth extraction prior to symptom onset and diverticulosis on chronic anticoagulation. Conclusion: SBG PJI is typically due to hematologic seeding. Colonoscopy should be pursued for patients with SBG PJI. Surgical treatment dictated by infection acuity and 6-week course of Ceftriaxone seems sufficient to control infection., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The in vitro activities of rifampin, rifabutin, rifapentine, and rifaximin were tested against 200 periprosthetic joint infection (PJI)-associated staphylococci. Seven rifampin-resistant isolates had MICs of ≥4 μg/ml. Three isolates had rifampin MICs of 0.25 to 1 μg/ml and harbored an Asp471Gly RpoB variant, suggesting that the CLSI rifampin-susceptible staphylococcal breakpoint of ≤1 μg/ml may be too high. The remaining isolates had rifampin MICs of ≤0.016 μg/ml, and the rifampin, rifabutin, rifapentine, and rifaximin minimum biofilm bactericidal concentrations (MBBC) for ≥50% of isolates were 8, 1, 2, and 4 μg/ml (for S. aureus ) and 2, 0.06, 0.25, and 0.5 μg/ml (for S. epidermidis ), respectively, for rifampin-susceptible isolates. Nonrifampin rifamycins have promising staphylococcal activity, including antibiofilm activity., (Copyright © 2019 American Society for Microbiology.)

Background: Hematopoietic stem cell transplantation (HSCT) recipients are at increased risk for infection. This study describes bone and joint infections (BJI) among HSCT recipients. Methods: We reviewed 5861 patients who underwent HSCT at Mayo Clinic, Rochester, MN from January 1, 2005 through January 1, 2015 for study inclusion. BJI was defined as native septic arthritis, prosthetic joint infection, osteomyelitis, and orthopedic implant infection. All adults with BJI after HSCT were included in the analysis. Results: Of 5861 patients, 33 (0.6%) developed BJI. Native joint septic arthritis was the most common BJI occurring in 15/33 (45.4%) patients. Patients were predominantly male (24/33, 72.7%), with median age of 58 (range 20-72) years. BJI was diagnosed a median of 39 (range 1-114) months after allogeneic (14/33, 42.4%) or autologous (19/33, 57.6%) HSCT. Organisms were recovered via tissue (24/27, 88.9%), synovial fluid (13/17, 76.5%), and/or blood cultures (16/25, 64%). Most underwent surgical debridement (23/33, 69.7%). Patients were followed a median of 78.3 months (range 74-119). Therapy was unsuccessful in 4/33 (12.1%), with death related to the underlying BJI in two (50%). Failure occurred a median of 3.4 (0.1-48.5) months from diagnosis. At last follow up, 7/33 (21.2%) patients were alive. Median overall survival was 13 months (0.07-70.6). Conclusion: BJI among HSCT recipients is infrequent. The most common infection is native joint septic arthritis. Pathogens appear similar to patients without HSCT. Treatment involving surgical-medical modalities is successful, with most patients surviving >1 year after BJI., Competing Interests: Competing Interests: One author (PK) has received funding from Amgen, Takeda and Sanofi., (© The author(s).)

Patients with febrile neutropenia (FN) often are subject to antibiotic and diagnostic test overuse. We sought to improve appropriate use of antimicrobials and diagnostic tests for patients with FN. We used a blended quality approach with Lean Six Sigma tools and iterative improvement of a clinical decision aid to guide providers through empirical antimicrobial selection and diagnostic evaluation of patients with FN during a yearlong period. We evaluated the incidence of nonadherence to best practice before, during, and after rollout of a clinical decision aid in conjunction with an educational initiative. At baseline, 71% of patients with FN had at least one critical deviation from best practice. During the project, the percentage decreased to 27.3%; 4 months after the project was completed, the percentage was 33.3% ( P = .04). A clinical decision aid can improve adherence to best practices for the empirical management of FN.

In this cohort of 51 patients managed with retained "destination spacers" after the resection of infected joint prostheses, the presence of preoperative sinus drainage was significantly associated with reinfection. Chronic antimicrobial suppression after destination-spacer retention did not significantly prevent reinfections., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Actinomyces prosthetic joint infections (APJIs) are rare and optimal medical and surgical treatment strategies are unknown. The purpose of our study was to characterize the demographics, risk factors, management and outcomes of patients with PJIs due to Actinomyces spp. Methods: Using a retrospective cohort study design, the medical records of all patients with Actinomyces spp. total hip or knee arthroplasty infection (APJI) seen at a single institution between January 1, 1969 and December 31, 2016 were reviewed. We abstracted information including patient demographics, co-morbidities, joint age, surgical history, microbiology, management and outcomes. A simultaneous literature search via PubMed was performed to identify cases of APJI published in literature and a descriptive analysis was performed. Results: Eleven cases were identified over a 47 year study period at our institution. Seven patients (64%) were female. The median age at the time of diagnosis of infection was 71 years (range, 57-89). The knee was involved in six cases (55%) followed by the hip in 5 (45 %) cases. Three cases had dentures, broken teeth, or poor dentition. Actinomyces odonotlyticus was the most commonly found subspecies at our institution. Median ESR and CRP values were 61mm/hr and 64 mg/L respectively. Eight (72%) patients were managed with 2 stage exchange. Most patients received a course of beta-lactam therapy for 6 weeks. Ten cases (91%) were free of failure after a median duration of follow-up of 2 years (range, 0.67 - 5 years). The median duration from joint arthroplasty to the onset of symptoms was 162 days, range (20-3318). Six (54%) had a history of prior PJI with a different microorganism at the same joint site and 4 patients had history of prior 2 stage exchange (36%). In the literature group, we identified 12 cases and the most common subspecies was Actinomyces israelii ; most patients underwent two stage exchange and were treated with 6 weeks of beta lactam antibiotics. Conclusions: Based on our observational study, Actinomyces PJI presents as a late complication of TJR, may be associated with prior PJI at the index joint and antecedent dental manipulation may portend as an additional risk factor. Treatment includes two stage exchange and beta- lactam therapy for 6weeks. These results will help clinicians in improved understanding and management of APJIs which although are rare but warrant special attention as population with implanted joint arthroplasties continues to rise., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: Povidone-iodine (PI) irrigation is often used prior to wound closure in total joint arthroplasty, but there are limited reports evaluating its efficacy in decreasing joint infections. The goal of this study was to compare the rate of any reoperation for infection (both superficial and deep) in primary total hip arthroplasty (THA) and primary total knee arthroplasty (TKA) among patients who did and did not receive PI irrigation prior to wound closure., Methods: Using our institution's total joint registry, we identified 5,534 primary THA and 6,204 primary TKA procedures performed from 2013 to 2017. Cases were grouped on the basis of whether or not the wound was irrigated with 1 L of 0.25% PI prior to closure. PI irrigation was used in 1,322 (24%) of the THA cases and in 2,410 (39%) of the TKA cases. The rates of reoperation for infection at 3 months and 1 year were compared between the 2 groups. The same comparisons were then performed using propensity scores to account for differences in baseline characteristics., Results: The rate of reoperation for infection as assessed at 3 months following THA was similar between those who received dilute PI irrigation (0.9%) and who did not (0.7%) (p = 0.7). At 1 year, the rate of reoperation for infection was similar between those who received dilute PI irrigation (0.7%) and those who did not (0.9%) (p = 0.6). After using the propensity score, there was no difference between the groups in the risk of septic reoperations. For TKA, the rate of reoperation as assessed at 3 months was similar between those who received dilute PI irrigation (0.8%) and those who did not (0.3%) (p = 0.06). At 1 year, there was a greater rate of reoperations for infection among those who received dilute PI irrigation (1.2%) compared with those who did not (0.6%) (p = 0.03). However, there was no difference in the risk of septic reoperations between the groups after using the propensity score., Conclusions: Despite enthusiasm for and progressive adoption of the use of dilute PI irrigation at our institution, there was not a significant reduction in the risk of reoperation for infection as assessed at 3 months and 1 year following primary THA and TKA., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Aims: There is little information regarding the risk of a patient developing prosthetic joint infection (PJI) after primary total knee arthroplasty (TKA) when the patient has previously experienced PJI of a TKA or total hip arthroplasty (THA) in another joint. The goal of this study was to compare the risk of PJI of primary TKA in this patient population against matched controls., Patients and Methods: We retrospectively reviewed 95 patients (102 primary TKAs) treated between 2000 and 2014 with a history of PJI in another TKA or THA. A total of 50 patients (53%) were female. Mean age was 69 years (45 to 88) with a mean body mass index (BMI) of 36 kg/m 2 (22 to 59). In total, 27% of patients were on chronic antibiotic suppression. Mean follow-up was six years (2 to 16). We 1:3 matched these (for age, sex, BMI, and surgical year) to 306 primary TKAs performed in 306 patients with a THA or TKA of another joint without a subsequent PJI. Competing risk with death was used for statistical analysis. Multivariate analysis was followed to evaluate risk factors for PJI in the study cohort., Results: The cumulative incidence of PJI in the study cohort (6.1%) was significantly higher than the matched cohort (2.6%) at ten years (hazard ratio (HR) 3.3; 95% confidence interval 1.18 to 8.97; p = 0.02). Host grade in the study group was not a significant risk factor for PJI. Patients on chronic suppression had a higher rate of PJI (HR 15; p = 0.002), with six of the seven patients developing PJI in the study group being on chronic suppression. The new infecting microorganism was the same as the previous in only two of seven patients., Conclusion: In this matched cohort study, patients undergoing a clean primary TKA with a history of TKA or THA PJI in another joint had a three-fold higher risk of PJI compared with matched controls with ten-year cumulative incidence of 6.1%. The risk of PJI was 15-fold higher in patients on chronic antibiotic suppression; further investigation into reasons for this and mitigation strategies are recommended. Cite this article: Bone Joint J 2019;101-B(7 Supple C):91-97.

Aims: The aims of this study were to characterize antibiotic choices for perioperative total knee arthroplasty (TKA) and total hip arthroplasty (THA) prophylaxis, assess antibiotic allergy testing efficacy, and determine rates of prosthetic joint infection (PJI) based on perioperative antibiotic regimen., Patients and Methods: We evaluated all patients undergoing primary TKA or THA at a single academic institution between January 2004 and May 2017, yielding 29 695 arthroplasties (22 705 patients), with 3411 arthroplasties in 2576 patients (11.5%) having undergone preoperative allergy testing. A series of institutional databases were combined to identify allergy consultation outcomes, perioperative antibiotic regimen, and infection-free survivorship until final follow-up., Results: Among 2576 allergy-tested patients, 2493 patients (97%) were cleared to use cephalosporins. For the entire cohort, 28 174 arthroplasties (94.9%) received cefazolin and 1521 (5.1%) received non-cefazolin antibiotics. Infection-free survivorship was significantly higher among arthroplasties receiving cefazolin compared with non-cefazolin antibiotics, with 0.06% higher survival free of infection at one month, 0.56% at two months, 0.61% at one year, and 1.19% at ten years (p < 0.001). Overall, the risk of PJI was 32% lower in patients treated with cefazolin after adjusting for the American Society of Anesthesiologists (ASA) classification, joint arthroplasty (TKA or THA), and body mass index (BMI; p < 0.001). The number needed to treat with cefazolin to prevent one PJI was 164 patients at one year and 84 patients at ten years. Therefore, potentially 6098 PJIs could be prevented by one year and 11 905 by ten years in a cohort of 1 000 000 primary TKA and THA patients., Conclusion: PJI rates are significantly higher when non-cefazolin antibiotics are used for perioperative TKA and THA prophylaxis, highlighting the positive impact of preoperative antibiotic allergy testing to increase cefazolin usage. Given the low rate of true penicillin allergy positivity, and the readily modifiable risk factor that antibiotic choice provides, we recommend perioperative testing and clearance for all patients presenting with penicillin and cephalosporin allergies. Cite this article: Bone Joint J 2019;101-B(6 Supple B):9-15.

Purpose: There are limited data on the effect of ceftriaxone on methotrexate clearance, with results of some studies indicating altered methotrexate pharmacokinetics with the administration of ceftriaxone. We describe 2 possible cases demonstrating an interaction between methotrexate and ceftriaxone, resulting in profound neutropenia., Summary: The decision to continue methotrexate therapy in the setting of surgery or during treatment of an active infection continues to be a topic of debate due to perceived negative effects on the healing process. Methotrexate is typically administered at a lower dose for inflammatory arthritis than for hematologic indications, thus having less immunosuppression potential. However, if methotrexate is continued during treatment of infection, drug interactions along with effects on the healing process should be considered. Ceftriaxone is commonly considered safe for long-term therapy due to its favorable adverse effect and drug interaction profile. Ceftriaxone is partially eliminated via organic anion transporters in the kidneys, leading to potential competition with methotrexate clearance in the renal tubules. Clinicians using these drugs concurrently should be aware of the potential for development of neutropenia and monitor patients receiving this combination closely., Conclusion: Two patients receiving ceftriaxone therapy in the setting of a joint infection developed profound neutropenia after resuming oral methotrexate therapy for inflammatory arthritis., (© American Society of Health-System Pharmacists 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cryptococcosis is a rare opportunistic infection increasingly associated with lymphoproliferative disorders. The clinical course and outcomes in these patients have not been extensively studied. We retrospectively reviewed charts of adult patients with lymphoproliferative disorders diagnosed with cryptococcal infections. A total of 34 patients were identified; 31 (91%) had a B-cell neoplasm and 3 (9%) had a T-cell neoplasm. The most frequent clinical syndrome was disseminated cryptococcal infection (38%), followed by pneumonia (29%). 74% received prior chemotherapy and the overall mortality in this group was nearly six-fold higher than chemotherapy naïve patients; 26% were chemotherapy naïve. After a median follow-up of nine months from the date of infection, 24 patients had died (71%). The overall mortality at 30-days and one year was 18% and 46%, respectively. The high mortality warrants future studies to identify those at highest risk. Clinicians should remain vigilant as early diagnosis and treatment are of utmost importance.

Background: Although there is abundant information about bacterial periprosthetic joint infections (PJIs), there is a notable paucity of information about fungal PJIs. The goals of this study are to describe the patient demographics, diagnostic findings, and treatment results of fungal PJIs after total joint arthroplasty., Methods: We identified 31 fungal PJIs (13 total hip arthroplasties and 18 total knee arthroplasties) in 31 patients treated between 1996 and 2014. This represented 0.9% of the 3525 PJIs treated at our institution during this time period. Candida species accounted for 81% of infections. The mean patient age at diagnosis of fungal PJI was 68 years. Mean follow-up after initiation of treatment was 4 years., Results: In the total hip arthroplasty cohort, survivorship free from all-cause revision or implant removal was 44% at 2 years. Survivorship free from reinfection was 38% at 2 years. Mean Harris hip score was 27 at final follow-up.In the total knee arthroplasty cohort, survivorship free from all-cause revision was 70% at 2 years. Survivorship free from reinfection was 76% at 2 years. Mean Knee Society scores were 36 at final follow-up., Conclusion: Fungal PJIs are rare (0.9% of diagnosed PJIs). Survivorship free of all-cause revision or implant removal was very low in the hip group (44% at 2 years), but slightly better in the knee group (70% at 2 years). Moreover, clinical outcomes were poor with high perioperative complication rates. Improved treatment regimens are needed for this unsolved clinical problem., (Copyright © 2018 Elsevier Inc. All rights reserved.)