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To minimize periprosthetic joint infection (PJI) risk, some clinicians prescribe extended antibiotic prophylaxis (EAP) following total joint arthroplasty (TJA). Given the limited evidence supporting EAP, we sought to evaluate impact of prophylactic antibiotic duration on PJI risk in a murine TJA model. A titanium prosthesis was implanted into the proximal tibia of 89 mice and inoculated with 10 2 colony forming units (cfu) of Staphylococcus aureus Xen36. Control mice (n = 20) did not receive antibiotics. Treated mice received either 24 h (n = 35) or 4 days (n = 34) of cefazolin prophylaxis. Cultures were obtained from the prostheses, tibia, femur, and knee tissues 3 weeks after surgery. All mice in the control group developed PJI. Both prophylaxis regimens reduced the rate of PJI relative to the control, with only 2/35 mice in the 24-h cohort (p < 0.0001) and 1/34 in 4-day cohort developing PJI (p < 0.0001). CFU counts from the prostheses, bone and knee tissues were reduced for the 24-h and 4-day prophylaxis cohorts relative to the control (p < 0.0001 for both). There was no difference in rates of PJI or CFU counts between the two prophylaxis cohorts (p = 0.58). Prophylactic cefazolin profoundly reduced rates of PJI in a murine model of TJA in which all control animals developed PJI. Extending cefazolin prophylaxis duration from 24 h to 4 days did not result in improved PJI rates or decreased bacterial loads in infected cases. While these results strongly support use of antibiotic prophylaxis for TJA, EAP did not appear to add benefit in the described mouse model., (© 2024 Orthopaedic Research Society.)

Background: Periprosthetic joint infections (PJIs) of total hip arthroplasty (THA) or total knee arthroplasty (TKA) may occur in the setting of an uninfected ipsilateral prosthetic joint. However, the risk to that uninfected ipsilateral joint is unknown. We analyzed the survivorship free from PJI in at risk THAs and TKAs following treatment of an ipsilateral knee or hip PJI, respectively., Methods: Using our institutional total joint registry, we identified 205 patients who underwent treatment for PJI (123 THAs and 83 TKAs) with an at-risk ipsilateral in situ knee or hip, respectively, between 2000 and 2019. In total, 54% of index PJIs were chronic and 46% were acute. The mean age was 70 years, 47% were female, and the mean body mass index was 32. Kaplan-Meier survivorship analyses were performed. Mean follow-up was 6 years., Results: The 5-year survivorship free of PJI in an at-risk THA after an ipsilateral TKA was treated for PJI was 97%. The 5-year survivorship free of PJI in an at-risk TKA when the ipsilateral THA was treated for PJI was 99%. Three PJIs occurred (2 THAs and 1 TKA), all over 1 year from the index ipsilateral PJI treatment. One hip PJI was an acute hematogenous infection that resulted from pneumonia. The other 2 new PJIs were caused by the same organism as the index PJI and were due to a failure of source control at the index joint., Conclusions: When diagnosed with PJI in a single joint, the risk of developing PJI in an ipsilateral prosthetic joint within 5 years was low (1 to 3% risk). In the rare event of an ipsilateral infection, all occurred greater than one year from the index PJI and 2 of 3 were with the same organism when source infection control failed., Level of Evidence: Prognostic Level III., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to perform a systematic review and meta-analysis to evaluate the association between tranexamic acid (TXA) use during primary total hip arthroplasty (THA) and primary total knee arthroplasty (TKA), and the risk of developing periprosthetic joint infection (PJI) after these procedures., Methods: A systematic review was carried out from inception to October 17, 2022. There were 6 studies that were ultimately included in the meta-analysis. The association between the development of PJI and TXA was analyzed using odds ratios (ORs) with 95% confidence intervals (CIs) and estimates of risk difference (RD). Subgroup analysis was performed to evaluate only studies reporting out to 90 days of follow-up versus more than 90 days of follow-up., Results: Among 2,098,469 arthroplasties, TXA utilization was associated with an overall lower risk of PJI (OR = 0.63 [95% CI 0.42 to 0.96], P < .001) and a 0.4% lower incidence of PJI (RD = -0.0038, 95% CI [-0.005 to -0.002], P < .001). When subgrouping the studies according to length of follow-up, TXA was associated with a lower risk of PJI (OR = 0.43 [95% CI 0.35 to 0.53], P < .001) and a 1% lower incidence of PJI (RD = -0.0095 [95% CI -0.013 to -0.005], P < .001) in patients followed for more than 90 days., Conclusions: This meta-analysis demonstrates that TXA use is associated with a reduced risk of PJI, with our RD analysis identifying an approximately 0.4% reduction in PJI rates with TXA use. These findings provide even more data to support the routine use of TXA during primary THA and primary TKA., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: To make an informed decision about total hip arthroplasty (THA), surgeons and patients need to understand the absolute and relative risks of periprosthetic joint infection (PJI). We sought to evaluate the long-term risk of PJI following primary THA stratified by body mass index (BMI) and PJI-related risk factors., Methods: We identified 21,550 primary THAs performed from 2000 to 2021 at a single institution. Patients were stratified as having 0, 1, or ≥ 2 PJI risk factors (diabetes, chronic kidney disease, nonprimary osteoarthritis, immunosuppression, or active smoking) and into BMI categories. The 15-year cumulative risk of PJI was evaluated by BMI and PJI risk factors., Results: For the entire cohort, the 15-year absolute risk of PJI was 2%. For patients who did not have PJI risk factors, the absolute risk of PJI at 15 years was 1% in normal weight, 2% in class III obesity, and 4% in class IV obesity. Patients who had class III and IV obesity had a 3-times and 9-times higher relative risk of PJI, respectively (P = .03, P < .001). Among patients who had ≥ 2 PJI risk factors, the absolute risk of PJI at 15 years was 2% in normal weight, 4% in class III obesity, and 18% in class IV obesity., Conclusions: Healthy patients who had class III and IV obesity had a 3-times and 9-times increased risk of PJI at 15 years relative to normal weight patients. However, the absolute risk of PJI at 15 years was 2 and 4%, respectively. Given emerging data questioning whether BMI modification decreases PJI risk, surgeons and patients must consider both a 3-times to 9-times increased relative risk of PJI and a 2 to 4% absolute risk of PJI at 15 years for healthy patients who had a BMI ≥ 40., Level of Evidence: IV., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Staphylococcus epidermidis is part of the commensal microbiota of the skin and mucous membranes, though it can also act as a pathogen in certain scenarios, causing a range of infections, including periprosthetic joint infection (PJI). Transcriptomic profiling may provide insights into mechanisms by which S. epidermidis adapts while in a pathogenic compared to a commensal state. Here, a total RNA-sequencing approach was used to profile and compare the transcriptomes of 19 paired PJI-associated S. epidermidis samples from an in vivo clinical source and grown in in vitro laboratory culture. Genomic comparison of PJI-associated and publicly available commensal-state isolates were also compared. Of the 1919 total transcripts found, 145 were from differentially expressed genes (DEGs) when comparing in vivo or in vitro samples. Forty-two transcripts were upregulated and 103 downregulated in in vivo samples. Of note, metal sequestration-associated genes, specifically those related to staphylopine activity (cntA, cntK, cntL, and cntM), were upregulated in a subset of clinical in vivo compared to laboratory grown in vitro samples. About 70% of the total transcripts and almost 50% of the DEGs identified have not yet been annotated. There were no significant genomic differences between known commensal and PJI-associated S. epidermidis isolates, suggesting that differential genomics may not play a role in S. epidermidis pathogenicity. In conclusion, this study provides insights into phenotypic alterations employed by S epidermidis to adapt to infective and non-infected microenvironments, potentially informing future therapeutic targets for related infections., (Published by Elsevier GmbH.)

Aims: Uncemented implants are now commonly used at reimplantation of a two-stage revision total hip arthoplasty (THA) following periprosthetic joint infection (PJI). However, there is a paucity of data on the performance of the most commonly used uncemented femoral implants - modular fluted tapered (MFT) femoral components - in this setting. This study evaluated implant survival, radiological results, and clinical outcomes in a large cohort of reimplantation THAs using MFT components., Methods: We identified 236 reimplantation THAs from a single tertiary care academic institution from September 2000 to September 2020. Two designs of MFT femoral components were used as part of an established two-stage exchange protocol for the treatment of PJI. Mean age at reimplantation was 65 years (SD 11), mean BMI was 32 kg/m 2 (SD 7), and 46% (n = 109) were female. Mean follow-up was seven years (SD 4). A competing risk model accounting for death was used., Results: The 15-year cumulative incidence of any revision was 24%. There were 48 revisions, with the most common reasons being dislocation (n = 25) and infection (n = 16). The 15-year cumulative incidence of any reoperation was 28%. Only 13 revisions involved the fluted tapered component (FTC), for a 15-year cumulative incidence of any FTC revision of 8%. Only two FTCs were revised for aseptic loosening, resulting in a 15-year cumulative incidence of FTC revision for aseptic loosening of 1%. Stem subsidence ≥ 5 mm occurred in 2% of unrevised cases. All stems were radiologically stable at most recent follow-up. Mean Harris Hip Score was 69 (SD 20) at most recent follow-up., Conclusion: This series demonstrated that MFT components were durable and reliable in the setting of two-stage reimplantation THA for infection. While the incidence of aseptic loosening was very low, the incidence of any revision was 24% at 15 years, primarily due to dislocation and recurrent PJI., Competing Interests: C. N. Carender sits on the editorial board of the Journal of Arthroplasty. M. P. Abdel receives the Andrew A. and Mary S. Sugg Professorship in Orthopedic Research, which funded this study, and reports royalties related to hip and knee implants from Stryker, royalties from OsteoRemedies, and publishing royalties from Springer, all of which are unrelated to this study. M. P. Abdel also sits on the Board of Directors for AAHKS, IOEN, and Mid-America. D. J. Berry reports royalties or licenses from DePuy, Elsevier, and Wolters Kluwer Health, consulting fees from Bodycad and DePuy, honoraria from AO Recon, stock or stock options in Bodycad, and research support from DePuy, all of which are unrelated to this study. D. J. Berry also reports leadership or fiduciary roles in Current Concepts in Joint Replacement (Hip Society and Knee Society), the International Hip Society, and the Orthopaedic Research and Educational Foundation. K. I. Perry is a paid consultant for DePuy Synthes, unrelated to this study. R. J. Sierra reports funding from Zimmer Biomet, OrthAlign, and LINK for this study, and royalties or licenses from Zimmer Biomet, OrthAlign, and LINK, consulting fees from OrthAlign, and a leadership or fiduciary role in the Muller Foundation and AAHKS, all unrelated to this study. R. T. Trousdale reports royalties from DePuy and Conformis, unrelated to this study., (© 2024 The British Editorial Society of Bone & Joint Surgery.)

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.)

Purpose: This pilot study aimed to use proteomic profiling of sonicate fluid samples to compare host response during Staphylococcus aureus-associated periprosthetic joint infection (PJI) and non-infected arthroplasty failure (NIAF) and identify potential novel biomarkers differentiating the two., Experimental Design: In this pilot study, eight sonicate fluid samples (four from NIAF and four from S. aureus PJI) were studied. Samples were reduced, alkylated, and trypsinized overnight, followed by analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) on a high-resolution Orbitrap Eclipse mass spectrometer. MaxQuant software suite was used for protein identification, filtering, and label-free quantitation., Results: Principal component analysis of the identified proteins clearly separated S. aureus PJI and NIAF samples. Overall, 810 proteins were identified based on their detection in at least three out of four samples from each group; 35 statistically significant differentially abundant proteins (DAPs) were found (two-sample t-test p-values ≤0.05 and log 2 fold-change values ≥2 or ≤-2). Gene ontology pathway analysis found that microbial defense responses, specifically those related to neutrophil activation, to be increased in S. aureus PJI compared to NIAF samples., Conclusion and Clinical Relevance: Proteomic profiling of sonicate fluid using LC-MS/MS differentiated S. aureus PJI and NIAF in this pilot study. Further work is needed using a larger sample size and including non-S. aureus PJI and a diversty of NIAF-types., (© 2023 Wiley-VCH GmbH.)

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.)

Background: Next-generation sequencing (NGS) is increasingly used for periprosthetic joint infection (PJI) diagnosis, but its clinical utility is poorly defined. Shotgun metagenomic sequencing (sNGS) has been reported to identify PJI pathogens undetected by culture in sonicate fluid. However, sNGS is complex and costly. Here, 16S ribosomal RNA (rRNA) gene-based targeted metagenomic sequencing (tNGS) was compared to sNGS of sonicate fluid for microbial detection and identification in patients with total hip arthroplasty (THA) and total knee arthroplasty (TKA) failure., Methods: A convenience sample of sonicate fluids derived from patients who had undergone THA or TKA removal, enriched with culture negative PJI cases, was tested. Samples had been previously tested by sNGS. For tNGS, samples were extracted, amplified by polymerase chain reaction targeting the V1 to V3 regions of the 16S rRNA gene, and sequenced on an Illumina MiSeq., Results: A total of 395 sonicate fluids, including 208 from subjects with PJI, were studied. Compared with sonicate fluid culture, tNGS had higher positive percent agreement (72.1 vs 52.9%, P < .001), detecting potential pathogens in 48.0% of culture-negative PJIs. There was no difference between the positive percent agreement of tNGS (72.1%) and sNGS (73.1%, P = .83)., Conclusions: 16S rRNA gene-based tNGS is a potential diagnostic tool for PJI pathogen identification in sonicate fluid from failed THAs and TKAs in culture-negative cases, with similar performance characteristics to sNGS., Competing Interests: Potential conflicts of interest. R. P. reports grants from ContraFect, TenNor Therapeutics Limited, and BioFire. R. P. is a consultant to Curetis, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST, Torus Biosystems, Day Zero Diagnostics, Mammoth Biosciences, and Qvella; monies are paid to Mayo Clinic. Mayo Clinic and R. P. have a relationship with Pathogenomix. R. P. is a consultant to Specific Technologies. R. P. has research supported by Adaptive Phage Therapeutics. Mayo Clinic has a royalty-bearing know-how agreement and equity in Adaptive Phage Therapeutics. R. P. is also a consultant to Netflix and CARB-X. In addition, R. P. has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued. R. P. receives honoraria from the NBME, Up-to-Date and the Infectious Diseases Board Review Course. M. A. reports royalties related to hip and knee implants from Stryker and a leadership or fiduciary role on the AAOS Board of Directors. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Although cellularity is traditionally assessed morphologically, deep sequencing approaches being used for microorganism detection may be able to provide information about cellularity. We hypothesized that cellularity predicted using CIBERSORTx (Stanford University), a transcriptomic-based cellular deconvolution tool, would differentiate between infectious and non-infectious arthroplasty failure., Methods: CIBERSORTx-derived cellularity profiles of 93 sonicate fluid samples, including 53 from subjects who underwent failed arthroplasties due to periprosthetic joint infection (PJI) (abbreviated for the purpose of this study as PJIF) and 40 from subjects who had undergone non-infectious arthroplasty failure (abbreviated NIAF) that had been subjected to bulk RNA sequencing were evaluated., Results: Samples from PJIF and NIAF subjects were differentially clustered by principal component analysis based on the cellularity profile. Twelve of the 22 individual predicted cellular fractions were differentially expressed in the PJIF cases compared with the NIAF cases, including increased predicted neutrophils (mean and standard error, 9.73% ± 1.06% and 0.81% ± 0.60%), activated mast cells (17.12% ± 1.51% and 4.11% ± 0.44%), and eosinophils (1.96% ± 0.37% and 0.42% ± 0.21%), and decreased predicted M0 macrophages (21.33% ± 1.51% and 39.75% ± 2.45%), M2 macrophages (3.56% ± 0.52% and 8.70% ± 1.08%), and regulatory T cells (1.57% ± 0.23% and 3.20% ± 0.34%). The predicted total granulocyte fraction was elevated in the PJIF cases (32.97% ± 2.13% and 11.76% ± 1.61%), and the samples from the NIAF cases had elevated predicted total macrophage and monocyte (34.71% ± 1.71% and 55.34% ± 2.37%) and total B cell fractions (5.89% ± 0.30% and 8.62% ± 0.86%). Receiver operating characteristic curve analysis identified predicted total granulocytes, neutrophils, and activated mast cells as highly able to differentiate between the PJIF cases and the NIAF cases. Within the PJIF cases, the total granulocyte, total macrophage and monocyte, M0 macrophage, and M2 macrophage fractions were differentially expressed in Staphylococcus aureus compared with Staphylococcus epidermidis -associated samples. Within the NIAF cases, the predicted total B cell, naïve B cell, plasma cell, and M2 macrophage fractions were differentially expressed among different causes of failure., Conclusions: CIBERSORTx can predict the cellularity of sonicate fluid using transcriptomic data, allowing for the evaluation of the underlying immune response during the PJIF and NIAF cases, without a need to phenotypically assess cell composition., 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/H320 )., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

The diagnosis of periprosthetic joint infection (PJI) is challenging, often requiring multiple clinical specimens and diagnostic techniques, some with prolonged result turnaround times. Here, the diagnostic performance of the Investigational Use Only (IUO) BioFire Joint Infection (JI) Panel was compared to 16S rRNA gene-based targeted metagenomic sequencing (tMGS) applied to synovial fluid for PJI diagnosis. Sixty synovial fluid samples from knee arthroplasty failure archived at -80°C were tested. Infectious Diseases Society of America (IDSA) diagnostic criteria were used to classify PJI. For culture-positive PJI with pathogens targeted by the JI panel, JI panel sensitivity was 91% (21/23; 95% confidence interval [CI], 73 to 98%), and tMGS sensitivity was 96% (23/24; 95% CI, 80 to 99%) ( P  = 0.56). Overall sensitivities of the JI panel and tMGS for PJI diagnosis were 56% (24/43; 95% CI, 41 to 70%) and 93% (41/44; 95% CI, 82 to 98%), respectively ( P  < 0.001). JI panel and tMGS overall specificities were 100% (16/16; 95% CI, 81 to 100%) and 94% (15/16; 95% CI, 72 to 99%), respectively. While the clinical sensitivity of the JI panel was excellent for on-panel microorganisms, overall sensitivity for PJI diagnosis was low due to the absence of Staphylococcus epidermidis, a common causative pathogen of PJI, on the panel. A PJI diagnostic algorithm for the use of both molecular tests is proposed.

Preoperative pathogen identification in patients with periprosthetic joint infection (PJI) is typically limited to synovial fluid culture. Whether sequencing-based approaches are of potential use in identification of pathogens in PJI, and if so which approach is ideal, is incompletely defined. The objective of the study was to analyze the accuracy of a 16S rRNA (rRNA) gene-based PCR followed by Sanger sequencing and/or targeted metagenomic sequencing approach (tMGS) performed on synovial fluid for PJI diagnosis. A retrospective study was conducted, analyzing synovial fluids tested between August 2020 and May 2021 at a single center. Subjects with hip, knee, shoulder, and elbow arthroplasties who had synovial fluid aspirated and clinically subjected to sequence-based testing and conventional culture were studied. A total of 154 subjects were included in the study; 118 had noninfectious arthroplasty failure (NIAF), while 36 had PJI. Clinical sensitivity and specificity for diagnosis of PJI were 69% and 100%, respectively, for the sequencing-based approach and 72% and 100%, respectively, for conventional culture ( P  = 0.74). The combination of both tests was more sensitive (83%) than culture alone ( P  = 0.04). Results of sequencing-based testing led to changes in treatment in four of 36 (11%) PJI subjects. Microbial identification was achieved using Sanger and next generation sequencing in 19 and 6 subjects, respectively. When combined with culture, the described 16S rRNA gene sequencing-based approach increased sensitivity compared to culture alone, suggesting its potential use in the diagnosis of PJI when synovial fluid culture is negative. IMPORTANCE Periprosthetic joint infection (PJI) is a dreadful complication of joint replacement. Noninvasive identification of infectious pathogens has been traditionnally limited to culture-based testing of synovial fluid which has poor sensitivity. Sanger and Next-generation sequencing (NGS) may be used for synovial fluid testing in PJI, but experience in routine practice is sparse. We used a targeted metagenomic sequencing approach for routine testing of synovial fluid involving NGS when Sanger sequencing had failed or was likely to fail. The objective of this study was to analyze the approach's performance for diagnosis of PJI in comparison to culture for testing synovial fluid. Overall, the sequencing-based approach was not superior to culture for diagnosis of PJI, but yielded positive results in some culture-negative samples.

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.)

Periprosthetic joint infection (PJI) is a major complication of total joint arthroplasty, typically necessitating surgical intervention and prolonged antimicrobial therapy. Currently, there is no perfect assay for PJI diagnosis. Proteomic profiling of sonicate fluid has the potential to differentiate PJI from non-infectious arthroplasty failure (NIAF) and possibly clinical subsets of PJI and/or NIAF. In this study, 200 sonicate fluid samples, including 90 from subjects with NIAF (23 aseptic loosening, 35 instability, 10 stiffness, five osteolysis, and 17 other) and 110 from subjects with PJI (40 Staphylococcus aureus, 40 Staphylococcus epidermidis, 10 Staphylococcus lugdunensis, 10 Streptococcus agalactiae, and 10 Enterococcus faecalis) were analyzed by proximity extension assay using the 92 protein Inflammation Panel from Olink Proteomics. Thirty-seven of the 92 proteins examined, including CCL20, OSM, EN-RAGE, IL8, and IL6, were differentially expressed in PJI versus NIAF sonicate fluid samples, with none of the 92 proteins differentially expressed between staphylococcal versus non-staphylococcal PJI, nor between the different types of NIAF studied. IL-17A and CCL11 were differentially expressed between PJI caused by different bacterial species, with IL-17A detected at higher levels in S. aureus compared to S. epidermidis and S. lugdunensis PJI, and CCL11 detected at higher levels in S. epidermidis compared to S. aureus and S. agalactiae PJI. Receiver operative characteristic curve analysis identified individual proteins and combinations of proteins that could differentiate PJI from NIAF. Overall, proteomic profiling using this small protein panel was able to differentiate between PJI and NIAF sonicate samples and provide a better understanding of the immune response during arthroplasty failure., (© 2022. The Author(s).)

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: Metabolic syndrome (MetS) represents a constellation of interrelated conditions including insulin resistance, abdominal obesity, hypertension, and dyslipidemia. The goals of this study are to determine the impact of MetS on implant survivorship, complications, and clinical outcomes after primary total hip arthroplasty (THA)., Methods: Utilizing our institutional total joint registry, 1,268 patients undergoing primary THA were identified with MetS based on the World Health Organization definition and matched 1:1 to those without MetS based on age, gender, and surgical year. MetS patients were further stratified according to the World Health Organization body mass index (BMI) classification to contextualize obesity. Kaplan-Meier analyses were utilized to compare survivorship free of any reoperation, revision, and complications. Clinical outcomes were assessed with Harris hip scores. Mean follow-up after THA was 5 years., Results: MetS patients had significantly worse 5-year survivorship free from any reoperation compared to those without MetS (93.5% vs 96.1%, respectively; hazard ratio [HR] 1.4, P = .04). When stratifying MetS and BMI classification, the BMI >40 kg/m 2 had significantly decreased 5-year implant survivorship free from any reoperation (85.9% vs 96.1%, HR 3.4, P < .001), any revision (91.7% vs 97.3%, HR 2.7, P < .001), and reoperation for periprosthetic joint infection (95% vs 99%, HR 5.1, P < .001). Both groups experienced significant and similar improvement in final Harris hip scores (P < .001)., Conclusion: Patients with MetS had a 1.4-fold increased risk of reoperation after primary THA compared to a matched cohort without the condition. MetS patients with a BMI >40 kg/m 2 had the highest risk of reoperation, and had a significantly higher revision and periprosthetic joint infection rates, suggesting that morbid obesity remains a critical, independent risk factor beyond MetS., Level of Evidence: Level 3, Case-control study., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Periprosthetic joint infection (PJI), a devastating complication of total joint replacement, is of incompletely understood pathogenesis and may sometimes be challenging to clinically distinguish from other causes of arthroplasty failure. We characterized human gene expression in 93 specimens derived from surfaces of resected arthroplasties, comparing transcriptomes of subjects with infection- versus non-infection-associated arthroplasty failure. Differential gene expression analysis confirmed 28 previously reported potential biomarkers of PJI, including bactericidal/permeability increasing protein (BPI), cathelicidin antimicrobial peptide (CAMP), C-C-motif chemokine ligand 3 (CCL3), 4(CCL4) and C-X-C-motif chemokine ligand 2 (CXCL2), colony stimulating factor 2 receptor beta (CSF2RB), colony stimulating factor 3 (CSF3), alpha-defensin (DEFA4), Fc fragment of IgG receptor 1B (CD64B), intercellular adhesion molecule 1 (ICAM1), interferon gamma (IFNG), interleukin 13 receptor subunit alpha 2 (IL13RA2), interleukin 17D (IL17D), interleukin 1 (IL1A, IL1B, IL1RN), interleukin 2 receptors (IL2RA, IL2RG), interleukin 5 receptor (IL5RA), interleukin 6 (IL6), interleukin 8 (IL8), lipopolysaccharide binding protein (LBP), lipocalin (LCN2), lactate dehydrogenase C (LDHC), lactotransferrin (LTF), matrix metallopeptidase 3 (MMP3), peptidase inhibitor 3 (PI3), and vascular endothelial growth factor A (VEGFA), and identified three novel molecules of potential diagnostic use for detection of PJI, namely C-C-motif chemokine ligand CCL20, coagulation factor VII (F7), and B cell receptor FCRL4. Comparative analysis of infections caused by staphylococci versus bacteria other than staphylococci and Staphylococcus aureus versus Staphylococcus epidermidis showed elevated expression of interleukin 13 (IL13), IL17D, and MMP3 in staphylococcal infections, and of IL1B, IL8, and platelet factor PF4V1 in S. aureus compared to S. epidermidis infections. Pathway analysis of over-represented genes suggested activation of host immune response and cellular maintenance and repair functions in response to invasion of infectious agents. The data presented provides new potential targets for diagnosis of PJI and for differentiation of PJI caused by different infectious agents., (Copyright © 2022 The Authors. Published by Elsevier B.V. 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.)

Objectives: Knowledge of the microbiological aetiology of periprosthetic joint infection (PJI) is essential to its management. Contemporary literature from the United States on this topic is lacking. This study aimed to identify the most common microorganisms associated with types of arthroplasty, the timing of infection, and clues to polymicrobial infection., Methods: We performed an analytical cross-sectional study of patients 18 years of age or older with hip or knee PJI diagnosed at our institution between 2010 and 2019. PJI was defined using the criteria adapted from those of the Musculoskeletal Infection Society. Cases included PJI associated with primary or revision arthroplasty and arthroplasty performed at our institution or elsewhere., Results: A total of 2067 episodes of PJI in 1651 patients were included. Monomicrobial infections represented 70% of episodes (n = 1448), with 25% being polymicrobial (n = 508) and the rest (5%, n = 111) culture-negative. The most common group causing PJI was coagulase-negative Staphylococcus species (other than S. ludgunensis) (37%, n = 761). The distribution of most common organisms was similar regardless of arthroplasty type. The S. aureus complex, Gram-negative bacteria, and anaerobic bacteria (other than Cutibacterium species) were more likely to be isolated than other organisms in the first year following index arthroplasty (OR 1.7, 95%CI 1.4-2.2; OR 1.5, 95%CI 1.1-2.0; and OR 1.5, 95%CI 1.0-2.2, respectively). The proportion of culture-negative PJIs was higher in primary than revision arthroplasty (6.5% versus 3%, p 0.0005). The presence of a sinus tract increased the probability of the isolation of more than one microorganism by almost three-fold (OR 2.6, 95%CI 2.0-3.3)., Conclusions: Joint age, presence of a sinus tract, and revision arthroplasties influenced PJI microbiology., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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

Although Streptococcus agalactiae periprosthetic joint infection (PJI) is not as prevalent as staphylococcal PJI, invasive S. agalactiae infection is not uncommon. Here, RNA-seq was used to perform transcriptomic analysis of S. agalactiae PJI using fluid derived from sonication of explanted arthroplasties of subjects with S. agalactiae PJI, with results compared to those of S. agalactiae strain NEM316 grown in vitro. A total of 227 genes with outlier expression were found (164 upregulated and 63 downregulated) between PJI sonicate fluid and in vitro conditions. Functional enrichment analysis showed genes involved in mobilome and inorganic ion transport and metabolism to be most enriched. Genes involved in nickel, copper, and zinc transport, were upregulated. Among known virulence factors, cyl operon genes, encoding β-hemolysin/cytolysin, were consistently highly expressed in PJI versus in vitro. The data presented provide insight into S. agalactiae PJI pathogenesis and may be a resource for identification of novel PJI therapeutics or vaccines against invasive S. agalactiae infections., (© 2021 Mayo Clinic. MicrobiologyOpen published by John Wiley & Sons Ltd.)

Background: Synchronous periprosthetic joint infections (PJIs) are a catastrophic complication with potentially high mortality. We aimed to report mortality, risk of reinfection, revision, reoperation, and implant survivorship after synchronous PJIs., Methods: We identified 34 patients treated for PJI in more than one joint within a single 90-day period from 1990 to 2018. PJIs involved bilateral knee arthroplasty (27), bilateral hip arthroplasty (4), 1 knee arthroplasty and 1 elbow arthroplasty (1), 1 knee arthroplasty and 1 shoulder arthroplasty (1), and bilateral hip and knee arthroplasty (1). Irrigation and debridement with component retention was performed in 23 patients, implant resection in 10 patients, and a combination of irrigation and debridement with component retention and implant resection in 1 patient. A competing risk model was used to analyze implant survivorship, and Kaplan-Meier survival was used for patient mortality. Mean follow-up was 6 years., Results: Mortality was high at 18% at 30 days and 27% at 1 year. The 1-year cumulative incidence of any reinfection was 13% and 27% at 5 years. The 1-year cumulative incidence of any revision or implant removal was 6% and 20% at 5 years. The 1-year cumulative incidence of unplanned reoperation was 25% and 35% at 5 years. Rheumatoid arthritis was associated with increased risk of mortality (HR 7, P < .01), as was liver disease (HR 4, P = .02)., Conclusion: In the largest series to date, patients with synchronous PJIs had a high 30-day mortality rate of 18%, and one-fourth underwent unplanned reoperation within the first year., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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.)

Transcriptomic analysis can provide insight as to how Staphylococcus aureus adapts to the environmental niche of periprosthetic joint infection (PJI), a challenging clinical infection. Here, in vivo RNA expression of eight S. aureus PJIs was compared with expression of the corresponding isolates in planktonic culture using a total RNA-sequencing approach. Expression varied among isolates, with a common trend showing increased expression of several ica-independent biofilm formation genes, including sdr, fnb, ebpS, and aaa; genes encoding enzymes and toxins, including coa, nuc, hlb, and hlgA/B/C; and genes facilitating acquisition of iron via the iron-binding molecule siderophore B (snb) and heme consumption protein (isd) pathways in PJI. Several antimicrobial resistance determinants were detected; although their presence correlated with phenotypic susceptibility of the associated isolates, no difference in expression between in vivo and in vitro conditions was identified., (Copyright © 2021 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: A simultaneous periprosthetic joint infection (PJI) of an ipsilateral hip and knee arthroplasty is a challenging complication of lower extremity reconstructive surgery. We evaluated the use of total femur antibiotic-impregnated polymethylmethacrylate (PMMA) bone cement spacers in the staged treatment of such limb-threatening PJIs., Methods: Thirteen patients were treated with a total femur antibiotic spacer. The mean age at the time of spacer placement was 65 years. Nine patients had polymicrobial PJIs. All spacers incorporated vancomycin (3.0 g/40 g PMMA) and gentamicin (3.6 g/40 g PMMA), while 8 also included amphotericin (150 mg/40 g PMMA). Eleven spacers were biarticular. Twelve spacers were implanted through one longitudinal incision, while 8 of 12 reimplantations occurred through 2 smaller, separate hip and knee incisions. Mean follow-up after reimplantation was 3 years., Results: Twelve (92%) patients underwent reimplantation of a total femur prosthesis at a mean of 26 weeks. One patient died of medical complications 41 days after spacer placement. At latest follow-up, 3 patients had experienced PJI recurrence managed with irrigation and debridement. One required acetabular component revision for instability. All 12 reimplanted patients retained the total femur prosthesis with no amputations. Eleven (91%) were ambulatory, and 7 (58%) remained on suppressive antibiotics., Conclusion: Total femur antibiotic spacers are a viable, but technically demanding, limb-salvage option for complex PJIs involving the ipsilateral hip and knee. In the largest series to date, there were no amputations and 75% of reimplanted patients remained infection-free. Radical debridement, antimicrobial diversity, prolonged spacer retention, and limiting recurrent soft tissue violation are potential tenets of success., Level of Evidence: IV., (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.

Aims: To describe the risk of periprosthetic joint infection (PJI) and reoperation in patients who have an acute, traumatic wound dehiscence following total knee arthroplasty (TKA)., Methods: From January 2002 to December 2018, 16,134 primary TKAs were performed at a single institution. A total of 26 patients (0.1%) had a traumatic wound dehiscence within the first 30 days. Mean age was 68 years (44 to 87), 38% (n = 10) were female, and mean BMI was 34 kg/m 2 (23 to 48). Median time to dehiscence was 13 days (interquartile range (IQR) 4 to 15). The dehiscence resulted from a fall in 22 patients and sudden flexion after staple removal in four. The arthrotomy was also disrupted in 58% (n = 15), including a complete extensor mechanism disruption in four knees. An irrigation and debridement with component retention (IDCR) was performed within 48 hours in 19 of 26 knees and two-thirds were discharged on antibiotic therapy. The mean follow-up was six years (2 to 15). The association of wound dehiscence and the risk of developing a PJI was analyzed., Results: Patients who sustained a traumatic wound dehiscence had a 6.5-fold increase in the risk of PJI (95% confidence interval (CI) 1.6 to 26.2; p = 0.008). With the small number of PJIs, no variables were found to be significant risk factors. However, there were no PJIs in any of the patients who were treated with IDCR and a course of antibiotics. Three knees required reoperation including one two-stage exchange for PJI, one repeat IDCR for PJI, and one revision for aseptic loosening of the tibial component., Conclusion: Despite having a traumatic wound dehiscence, the risk of PJI was low, but much higher than experienced in all other TKAs during the same period. We recommend urgent IDCR and a course of postoperative antibiotics to decrease the risk of PJI. A traumatic wound dehiscence increases risk of PJI by 6.5-fold. Cite this article: Bone Joint J  2021;103-B(6 Supple A):191-195.

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.)

Introduction: Current diagnostic criteria for arthrofibrosis are limited. Since many patients will be aspirated during their clinical course, synovial fluid analysis may supplement current diagnostic criteria for arthrofibrosis. The goal of this study was to determine a unique synovial fluid and inflammatory marker profile for diagnosing arthrofibrosis., Hypothesis: Patients with arthrofibrosis following total knee arthroplasty will have a unique synovial fluid aspirate profile compared to control patients to aid in diagnosis., Materials and Methods: Between 2013 and 2017, 32 patients (32 total knee arthroplasties [TKAs]) underwent revision TKAs for arthrofibrosis. Fourteen patients had pre-revision aspirations. They were 2:1 matched based on age, sex, body mass index (BMI), and year of revision to 28 patients who underwent aseptic revision TKAs for reasons other than arthrofibrosis (control group). Mean age at revision was 66years, with 64% males., Results: In TKAs revised for arthrofibrosis, mean total cell count was 828cells/uL. These aspirates contained a mean distribution of 46% macrophages (range: 4-76%), 31% lymphocytes (range: 11-68%), 21% neutrophils (range: 0-75%), 1% other cells (mainly synovial cells; range: 0-11%), and 1% eosinophils (range: 0-7%). There was no significant difference in mean total cell count (p=0.8) or mean distribution of macrophages (p=0.6), lymphocytes (p=0.1), neutrophils (p=0.2), eosinophils (p>0.9), or serum inflammatory markers (p>0.7) when compared to controls. All aspirations were culture negative for infection., Discussion: The profile of arthrofibrotic synovial fluid aspirates and serum inflammatory marker values were similar to patients revised for non-arthrofibrotic aseptic etiologies. This suggests synovial fluid and serum inflammatory markers in non-infected knees with arthrofibrosis should expect to have characteristics similar to synovial fluid and inflammatory marker profiles in other aseptic diagnoses., Level of Evidence: III; retrospective case-control study., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

There is interest in novel synovial fluid biomarkers for the detection of periprosthetic joint infection (PJI). Here, we assessed the diagnostic accuracy of 23 simple or sophisticated synovial fluid biomarkers for periprosthetic hip or knee infection detection. One hundred seven subjects were studied, 57 of whom had aseptic failure (AF) and 50 PJI. The following synovial fluid biomarkers were tested using spectrophotometric assays, immunoassays, lateral flow tests, or test strips: leukocyte count, monocyte percentage, lymphocyte percentage, neutrophil percentage, C-reactive protein (CRP), glucose, lactate, granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin-1β (IL-1β), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IL-23, tumor necrosis factor-α, α-defensin, and leukocyte esterase. The best-performing synovial fluid biomarkers to differentiate PJI from AF-that is, those with highest area under the curve compared to all other biomarkers-were leukocyte count, percent neutrophils and percent monocytes, CRP, and α-defensin (P < .0001)., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

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: 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.)

Aims: Arthrodesis is rarely used as a salvage procedure for patients with a chronically infected total knee arthroplasty (TKA), and little information is available about the outcome. The aim of this study was to assess the reliability, durability, and safety of this procedure as the definitive treatment for complex, chronically infected TKA, in a current series of patients., Methods: We retrospectively identified 41 patients (41 TKAs) with a complex infected TKA, who were treated between 2002 and 2016 using a deliberate, two-stage knee arthrodesis. Their mean age was 64 years (34 to 88) and their mean body mass index (BMI) was 39 kg/m 2 (25 to 79). The mean follow-up was four years (2 to 9). The extensor mechanism (EM) was deficient in 27 patients (66%) and flap cover was required in 14 (34%). Most patients were host grade B (56%) or C (29%), and limb grade 3 (71%), according to the classification of McPherson et al. A total of 12 patients (29%) had polymicrobial infections and 20 (49%) had multi-drug resistant organisms; fixation involved an intramedullary nail in 25 (61%), an external fixator in ten (24%), and dual plates in six (15%)., Results: Survivorship free from amputation, persistent infection, and reoperation, other than removal of an external fixator, at five years was 95% (95% confidence interval (CI) 89% to 100%), 85% (95% CI 75% to 95%), and 64% (95% CI 46% to 82%), respectively. Reoperation, other than removal of an external fixator, occurred in 13 patients (32%). After the initial treatment, radiological nonunion developed in ten knees (24%). Nonunion was significantly correlated with persistent infection (p = 0.006) and external fixation (p = 0.005). Of those patients who achieved limb salvage, 34 (87%) remained mobile and 31 (79%) had 'absent' or 'minimal' pain ratings., Conclusion: Knee arthrodesis using a two-stage protocol achieved a survivorship free from amputation for persistent infection of 95% at five years with 87% of patients were mobile at final follow-up. However, early reoperation was common (32%). This is not surprising as this series included worst-case infected TKAs in which two-thirds of the patients had a disrupted EM, one-third required flap cover, and most had polymicrobial or multi-drug resistant organisms. Cite this article: Bone Joint J 2020;102-B(6 Supple A):170-175.

Two-stage exchange arthroplasty remains the gold standard for chronic total knee arthroplasty (TKA) and total hip arthroplasty infections in North America. Cement spacers impregnated with high-dose antibiotics have been successfully used in the interim period of the 2-stage exchange process. A number of spacers have been described; however, this article will focus on articulating spacers. In the presence of an intact extensor mechanism (for TKA), reasonable soft tissue envelope, and adequate bone, articulating antibiotic spacers provide several advantages. These include an infection eradication rate of approximately 90%, higher range of motion after reimplantation, and lower complication rates when compared with nonarticulating spacers. In the appropriate patient, articulating antibiotic spacers are an effective and a safe treatment for infected TKAs and total hip arthroplasties., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Resection arthroplasty of the hip is considered a viable option after multiple failed attempts to eradicate a prosthetic joint infection (PJI). However, much less information about resection arthroplasty of the knee is available. The goals of this study were to determine the success of infection eradication with a resection arthroplasty of the knee and subsequent functional outcomes in this group., Methods: We retrospectively identified 25 knees (23 patients) treated with resection arthroplasty of the knee for PJI performed at a single institution between 1974 and 2016. The mean age at resection arthroplasty was 65 years. The mean body mass index was 37 kg/m 2 , and the mean Charleston Comorbidity Index was 5. Patients had a mean of 5 operations on the knee (mean of 3 operations for infection) before the resection arthroplasty. Failure to eradicate the infection was defined as any reoperation for infection. Clinical outcomes were assessed via ambulatory status, use of gait aids, and ongoing pain. The mean follow-up was 4 years., Results: At most recent follow-up, 84% (21 of 25) of knees were free of infection. Three patients had recurrent infection within the first year, and 1 patient had a late infection at 4 years postoperatively. However, only 1 patient required a subsequent amputation. Forty-five percent were community ambulators, 35% were household ambulators, and 20% were only able to transfer. All patients required knee bracing and assistive devices. Fifteen percent of patients were using long-term narcotics., Conclusion: This large series demonstrates the results of selected use of resection arthroplasty as a treatment for recalcitrant periprosthetic knee infections that have failed multiple attempts to eradicate an ongoing PJI. The resection definitively solved the infection in 84% of patients. Functional results were variable but surprisingly good in some. All patients required bracing and assistive devices., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.)

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: Postoperative infection remains a major challenge in revision total hip arthroplasty (THA) and revision total knee arthroplasty (TKA). Wound irrigation with dilute povidone-iodine (PI) solution has emerged as a simple, inexpensive, and potentially successful means of reducing postoperative infections. The aim of this study was to assess its effectiveness in reducing infection following revision THA and TKA in, to our knowledge, the largest revision cohort to date., Methods: Using our institution's total joint registry, we identified 1,402 revision THAs and 1,482 revision TKAs performed during the study period (2013, when the PI irrigation protocol was first implemented, to 2017). The PI lavage protocol was employed in 27% of the revision THA cases and 34% of the revision TKA cases; in the remaining cases, the protocol was not used. Demographics, comorbid conditions, underlying surgical diagnoses, and whether the revision was for a septic or an aseptic etiology were compared between the groups (use or no use of PI irrigation). Any reoperation due to infection, as assessed at 3 and 12 months following revision arthroplasty, was compared between the groups and propensity scores were calculated to account for differences in baseline characteristics between the groups., Results: After adjusting for baseline differences between the groups using the propensity-score weighted models, we found no significant difference in the rate of reoperation for infection at 3 months (p = 0.58 for revision THA, and p = 0.06 for revision TKA) and at 12 months (p = 0.78 for revision THA, and p = 0.06 for revision TKA). Nonetheless, the hazard ratios from the propensity-score model trended higher for patients who received PI lavage: 1.6 and 1.3 for revision THA at 3 and 12 months, respectively, and 2.9 at both 3 and 12 months for revision TKA., Conclusions: PI wound lavage demonstrated no benefit in reducing any reoperation for infection following revision THA and TKA. Moreover, the trend toward higher rates for reoperation for infection among patients who received PI irrigation merit further consideration., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

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.

Background: Two-stage exchange is the most common form of treatment of chronic infection following total hip arthroplasty (THA). We examined the prevalence of, and risk factors associated with, hip instability following 2-stage exchange as well as the fate of reimplanted hip prostheses that dislocated., Methods: Data on 515 2-stage exchange THAs performed between 2000 and 2014 at a single institution were retrospectively reviewed. Risk factors for instability as well as postoperative reoperations and revisions were analyzed. The impact of dislocation on these outcomes was evaluated as well. The mean age at the time of reimplantation was 65 years, and the mean duration of follow-up was 5 years (range, 2 to 15 years)., Results: Dislocation occurred in 52 hips following reimplantation (cumulative probability = 8.9% at 1 year). There was a higher risk of instability in women (hazard ratio [HR] = 1.8, p = 0.038) and in those who had a history of dislocation prior to the 2-stage revision (HR = 5.1, p < 0.001). Younger age, body mass index, number of previous operations, spacer type, surgical approach, use of a constrained liner, femoral head diameter, and persistent or recurrent infection were not found to be significant risk factors. Patients with an absent or ununited greater trochanter or abductor deficiency also had a higher rate of dislocation (HR = 30, p < 0.001), as did patients who underwent reimplantation with a megaprosthesis (HR = 6.0, p < 0.001). The risk of additional reoperations (HR = 121, p < 0.001) and revision surgery (HR = 13, p < 0.001) was significantly higher in patients who experienced a dislocation after the 2-stage exchange., Conclusions: Dislocation after 2-stage exchange THA continues to be a major concern, with the 1-year cumulative probability found to be 9% in the present study. Female sex, a history of dislocation, an absent or ununited greater trochanter or abductor deficiency, and reimplantation with a megaprosthesis were identified as risk factors for dislocation. There is a remarkable 121-fold increase in the rate of reoperations and a 13-fold increase in the rate of revisions in hips that dislocated after 2-stage exchange THA., Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Background: For patients undergoing 2-stage exchange for the treatment of periprosthetic joint infection (PJI) following total knee arthroplasty, the long-term risk of reinfection and mechanical failure and long-term clinical outcomes are not well known. The purpose of our study was to determine the long-term clinical results of 2-stage exchange for PJI following total knee arthroplasty., Methods: We identified 245 knees that had undergone total knee arthroplasty and were subsequently treated with 2-stage exchange due to infection during the period of 1991 to 2006; the cohort had no prior treatment for PJI. Major, or 4 of 6 minor, Musculoskeletal Infection Society (MSIS) diagnostic criteria were fulfilled by 179 (73%) of the knees. The cumulative incidence of reinfection and of aseptic revision, accounting for the competing risk of death, were calculated. Risk factors for reinfection were evaluated using Cox proportional hazards regression. Knee Society Score (KSS) values were calculated. The mean age at spacer insertion was 68 years; 50% of the patients were female. The mean follow-up was 14 years (range, 2 to 25 years) following reimplantation., Results: The cumulative incidence of reinfection was 4% at 1 year, 14% at 5 years, 16% at 10 years, and 17% at 15 years. Factors that were predictive of reinfection included a body mass index of ≥30 kg/m (hazard ratio [HR], 3.1; p < 0.01), previous revision surgery (HR, 2.8; p < 0.01), and a McPherson host grade of C (HR, 2.5; p = 0.04). The cumulative incidence of aseptic revision for loosening was 2% at 5 years, 5% at 10 years, and 7% at 15 years. Femoral (HR, 5.0; p = 0.04) and tibial (HR, 6.7; p < 0.01) bone-grafting at reimplantation were predictive of aseptic failure. The most common complications were wound-healing issues, requiring reoperation in 12 (5%) of the knees. The rate of death at 2 years following reimplantation was 11%. The mean KSS improved from 45 at PJI diagnosis to 76 at 10 years following reimplantation (p < 0.01)., Conclusions: Long-term reinfection rates following 2-stage exchange for PJI after total knee arthroplasty were similar to those of shorter-term reports and were maintained out to 15 years. Mechanical failure rates were low if bone loss was addressed at the time of reimplantation. Improvements in clinical outcomes were maintained at long-term follow-up., Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Revisions TKAs are being completed with uncemented constructs more frequently. We hypothesized that tantalum cones could be an efficient carrier of antibiotics in uncemented procedures. We aimed to compare the release of vancomycin between (i) tantalum and smooth stainless cylinders; (ii) different concentrations of vancomycin; and (iii) different durations of bathing. Specifically designed tantalum cylinders were bathed in a vancomycin solution with various durations of baths. We investigated rinses between each interval as well as the dose of vancomycin. Vancomycin concentrations were determined in each group by fluorescence polarization immunoassay at different intervals (1 h, days 1, 2, 3, 5). At 1 h, the mean vancomycin concentration for the 1-hour soaking group was 3,172 μg/ml, whereas mean concentration for the smooth stainless steel group was 39.37 μg/ml (p < 0.001). The rinsing group showed a significantly lower concentration at 1 h and 1 day (p < 0.05). The 2-gram vancomycin group showed no difference at days 1, 2, and 3 compared to the 1-hour group. The 5, 15, and 30-minute bathing groups showed significantly lower vancomycin concentrations at all-time points. All vancomycin concentrations at day 3 were superior to the minimal inhibitory concentration of Staphyloccocus aureus. The mean concentration of vancomycin depends on the material, duration of bathing, the rinsing effect, and the drug dose. Our in-vitro study is the first to show that porous tantalum cylinders allow antibiotic carriage and progressive release. If appearing in vivo, in a similar extent, this intrinsic property might be useful to prevent and/or treat peri-prosthetic joint infection. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:308-312, 2019., (© 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)