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Focuses on Australia's international relations. Benefits and drawbacks of the country's relationship with the United States; Inadequacies of multilateralism; U.S. policy of preventive intervention; Factors reducing the role of geography.

Objectives: To identify global differences in the use of suppressive antimicrobial therapy (SAT) in the management of prosthetic joint infection (PJI)., Methods: An online survey was designed to investigate clinician's approach to SAT for PJI, including indications, preferred antimicrobial drugs, dosing, treatment duration and follow-up. The survey was distributed to members of four international (bone and joint) infection societies and study groups., Results: Respondents comprised 330 physicians (204 infectious diseases specialists, 110 orthopedic surgeons, 23 clinical microbiologists) from 43 different countries (Europe, n = 134, 41%; Oceania n = 112, 34%; North America, n = 51, 16%; other, n = 33, 10%; total response rate 20%). After debridement, antibiotics and implant retention (DAIR) or one-stage revision, SAT would be initiated often or almost always by 38% of respondents from North America, but only in 6% from Europe and 7% from Oceania. First choices of SAT for staphylococcal PJI were oral cephalosporins (39%) and tetracyclines (31%) in North America; tetracyclines (27%) and anti-staphylococcal penicillins (22%) in Europe; and anti-staphylococcal penicillins (55%) in Oceania. There was no global or regional preferred SAT regimen for Gram-negative PJI. Of all respondents, dosage of SAT was never lowered (n = 126, 38%), lowered for specific antibiotics (n = 125, 38%) or lowered for all antibiotics (n = 79, 24%). SAT was prescribed for a lifelong duration (n = 43, 13%), a fixed duration (range 6 months-3 years) (n = 104, 32%) or for an undetermined duration (n = 154, 47%)., Conclusions: Approach to SAT in PJI is highly regional, with no consensus regarding the indication, selection, dose, or duration of SAT between physicians worldwide. This reflects the paucity of data and need for high quality studies to define the optimal use of SAT in the treatment of patients with PJI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Diagnosis of periprosthetic joint infection (PJI) in patients with inflammatory arthritis (IA) is challenging, as features of IA flares can mimic infection. We aimed to cross-sectionally determine if the optimal tests to diagnose PJI in osteoarthritis were present in patients with IA flares., Methods: We enrolled patients from October 2020 to July 2022 in 3 groups: ( a ) PJI-total joint arthroplasty patients undergoing revision for infection, ( b ) IA Flare-IA patients with a flaring native joint, and ( c ) IA Aseptic-total joint arthroplasty patients with IA undergoing aseptic arthroplasty revision. We compared blood and synovial fluid markers between the cohorts using Kruskal-Wallis and Fisher exact tests to assess marker sensitivity and specificity., Results: Of 52 cases overall, 40% had rheumatoid arthritis, 20% psoriatic arthritis, and 11% osteoarthritis (in PJI group). PJI cases had higher C-reactive protein (CRP) and synovial fluid polymorphonuclear neutrophil percentage (%PMN). Alpha-defensin tested positive in 93% of PJI cases, 20% of IA Flares, and 6% of IA Aseptic ( p < 0.01). Synovial white blood cell count >3000/μL and positive alpha-defensin were highly sensitive (100%) in diagnosing infection; however, specificity was 50% for white blood cell counts and 79% for alpha-defensin. PJI diagnosis was nearly 5 times more likely with positive alpha-defensin and almost 6 times more likely with %PMNs >80. Blood markers interleukin-6, procalcitonin, and d -dimer were neither sensitive nor specific, whereas erythrocyte sedimentation rate and CRP showed 80% sensitivity, but 47% and 58% respective specificities., Conclusions: Although synovial %PMNs, CRP, and alpha-defensin are sensitive tests for diagnosing PJI, they are less specific and may be positive in IA flares., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cefazolin is the standard of care for perioperative antibiotic prophylaxis in total joint arthroplasty (TJA) in the United States. The potential allergic cross-reactivity between cefazolin and penicillin causes uncertainty regarding optimal antibiotic choice in patients who have a reported penicillin allergy (rPCNA). The purpose of this study was to determine the safety of perioperative cefazolin in PCNA patients undergoing primary TJA., Methods: We identified all patients (n = 49,842) undergoing primary total hip arthroplasty (n = 25,659) or total knee arthroplasty (n = 24,183) from 2016 to 2022 who received perioperative intravenous antibiotic prophylaxis. Patients who had an rPCNA (n = 5,508) who received cefazolin (n = 4,938, 89.7%) were compared to rPCNA patients who did not (n = 570, 10.3%), and to patients who did not have an rPCNA (n = 43,359). The primary outcome was the rate of allergic reactions within 72 hours postoperatively. Secondary outcomes included the rates of superficial infections, deep infections, and Clostridioides difficile infections within 90 days., Results: The rate of allergic reactions was 0.1% (n = 5) in rPCNA patients who received cefazolin, compared to 0.2% (n = 1) in rPCNA patients who did not (P = .48) and 0.02% (n = 11) in patients who have no rPCNA (P = .02). Allergic reactions were mild in all 5 rPCNA patients who received cefazolin and were characterized by cutaneous symptoms (n = 4) or dyspnea in the absence of respiratory distress (n = 1) that resolved promptly with antibiotic discontinuation and administration of antihistamines and/or corticosteroids. We observed no differences in the rates of superficial infections (0.1 versus 0.2%, P = .58), deep infections (0.3 versus 0.4%, P = .68), or C difficile infections (0.04% versus 0%, P = .99) within 90 days in rPCNA patients who received cefazolin versus alternative perioperative antibiotics., Conclusions: In this series of more than 5,500 patients who had an rPCNA undergoing primary TJA, perioperative prophylaxis with cefazolin resulted in a 0.1% incidence of allergic reactions that were clinically indolent. Cefazolin can be safely administered to most patients, independent of rPCNA severity., Level of Evidence: III., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: We present results from a 2-site, randomized clinical trial to assess the efficacy of a brief intervention (As Safe As Possible [ASAP]), a safety plan phone application (BRITE), and their combination on suicide attempts, suicidal ideation, non-suicidal self-injury, re-hospitalizations. and suicidal events among adolescents., Method: Adolescents (n= 240; 12-17 years of age) who were hospitalized for suicidal ideation with plan and/or intent, and/or suicide attempt, were assigned to 1 of 4 treatment conditions in a 2 by 2 design: ASAP+BRITE app+treatment as usual (TAU); (2) BRITE+TAU; (3) ASAP+TAU; and (4) TAU alone. Independent evaluators assessed suicidal ideation and behavior at 4, 12, and 24 weeks using the Columbia-Suicide Severity Rating Scale (C-SSRS) and re-hospitalization using the Child and Adolescent Services Assessment (CASA)., Results: No group differences were found on primary outcomes, except that ASAP participants were less likely to be re-hospitalized over 6 months (15.6%, vs 26.5%, p = .046). Participants hospitalized for an attempt and assigned to BRITE had a lower rate of subsequent attempts (odds ratio [OR] = 0.16, p = .01) and a greater time to attempt (hazard ratio [HR] = 0.20, p = .02). ASAP+BRITE, albeit not statistically significant, was most consistently associated with a reduction (60% reduction) in suicide attempts., Conclusion: ASAP, BRITE, and their combination are equally effective at decreasing risk for suicidal events 6 months post hospital discharge among suicidal adolescents; the ASAP intervention (with or without BRITE) was associated with lower rates of re-hospitalization. The BRITE app in youth hospitalized for suicide attempt had promising outcomes in regard to future attempts., Diversity & Inclusion Statement: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. The research was performed with permission from the University of Pittsburgh Institutional Review Board and the University of Texas Institutional Review Board. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work., Clinical Trials Registration Information: Establishing Efficacy of an Inpatient Intervention and Phone App to Reduce Suicidal Risk (ASAP+BRITE); https://clinicaltrials.gov/study/; NCT03825588., (Copyright © 2024 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background : Variability in the definition of treatment success poses difficulty when assessing the reported efficacy of treatments for hip and knee periprosthetic joint infection (PJI). To address this problem, we determined how definitions of PJI treatment success have changed over time and how this has affected published rates of success after one-stage and two-stage treatments for hip and knee PJI. Methods : A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted to identify one-stage and two-stage revision hip and knee PJI publications in major databases (2006-2021). Definition of treatment success, based on Musculoskeletal Infection Society tier criteria, was identified for each study. Publication year, number of patients, minimum follow-up, and study quality were also recorded. The association of success definitions and treatment success rate was measured using multi-variable meta-regression. Results : Study quality remained unchanged in the 245 publications included. Over time, no antibiotics (tier 1) and no further surgery (tier 3) (40.7 % and 54.5 %, respectively) became the two dominant criteria. After controlling for type of surgery, study quality, study design, follow-up, and year of publication, studies with less strict success definitions (tier 3) reported slightly higher odds ratios of 1.05 [1.01, 1.10] ( p = 0.009 ) in terms of treatment success rates compared to tier 1. Conclusions : PJI researchers have gravitated towards tier-1 and tier-3 definitions of treatment success. While studies with stricter definitions had lower PJI treatment success, the clinical significance of this is unclear. Study quality, reflected in the methodological index for non-randomized studies (MINORS) score, did not improve. We advocate for improving PJI study quality, including clarification of the definition of treatment success., Competing Interests: The contact author has declared that none of the authors has any competing interests., (Copyright: © 2024 Eytan M. Debbi et al.)

Abstract: Although well-accepted clinical practice guidelines exist for the diagnosis of prosthetic joint infection (PJI), little is known about the quality of diagnosis for PJI. The identification of quality gaps in the diagnosis of PJI would facilitate the development of care structures and processes to shorten time to diagnosis and reduce the significant morbidity, mortality, and economic burden associated with this condition. Hence, we sought to develop valid clinical quality measures to improve the timeliness and accuracy of PJI diagnosis. We convened a nine-member multidisciplinary national panel of PJI experts including orthopedic surgeons, infectious disease specialists, an emergency medicine physician, and a patient previously treated for PJI to review, discuss, and rate the validity of proposed measures using a modification of the RAND-UCLA appropriateness method. In total, 57 permutations of six proposed measures were rated. Populations considered to be at high enough risk for PJI that certain care processes should always be performed were identified by the panel. Among the proposed quality measures, the panel rated five as valid. These novel clinical quality measures could provide insight into care gaps in the diagnosis of PJI., (Copyright © 2024 Wolters Kluwer Health, Inc.)

Background: There remains inconsistent data about the association of surgical approach and periprosthetic joint infection (PJI). We sought to evaluate the risk of reoperation for superficial infection and PJI after primary total hip arthroplasty (THA) in a multivariate model., Methods: We reviewed 16,500 primary THAs, collecting data on surgical approach and all reoperations within 1 year for superficial infection (n = 36) or PJI (n = 70). Considering superficial infection and PJI separately, we used Kaplan-Meier survivorship to assess survival free from reoperation and a Cox Proportional Hazards multivariate models to assess risk factors for reoperation., Results: Between direct anterior approach (DAA) (N = 3,351) and PLA (N = 13,149) cohorts, rates of superficial infection (0.4 versus 0.2%) and PJI (0.3 versus 0.5%) were low and survivorship free from reoperation for superficial infection (99.6 versus 99.8%) and PJI (99.4 versus 99.7%) were excellent at both 1 and 2 years. The risk of developing superficial infection increased with high body mass index (BMI) (hazard ratio [HR] = 1.1 per unit increase, P = .003), DAA (HR = 2.7, P = .01), and smoking status (HR = 2.9, P = .03). The risk of developing PJI increased with the high BMI (HR = 1.04, P = .03), but not surgical approach (HR = 0.68, P = .3)., Conclusion: In this study of 16,500 primary THAs, DAA was independently associated with an elevated risk of superficial infection reoperation compared to the PLA, but there was no association between surgical approach and PJI. An elevated patient BMI was the strongest risk factor for superficial infection and PJI in our cohort., Level of Evidence: III, retrospective cohort study., (Copyright © 2023. Published by Elsevier Inc.)

Background: Patients with inflammatory arthritis are at increased risk of prosthetic joint infections (PJIs), but diagnosis in these patients can be challenging because active inflammatory arthritis produces elevated inflammatory markers that may mimic those seen in PJI. Purpose : In this pilot study, we sought to identify the clinical, microbiologic, and histopathologic features of culture-positive and culture-negative PJI in patients with inflammatory arthritis who underwent total hip arthroplasty (THA) or total knee arthroplasty (TKA). We also sought to obtain preliminary data to support a definitive study of optimal methods for PJI diagnosis in patients with inflammatory arthritis. Methods : We performed a retrospective analysis of TKA and THA patients treated for PJI from 2009 to 2018 at a single tertiary care orthopedic institution. Data were extracted from a longitudinally maintained hospital infection database. We reviewed hematoxylin and eosin slides of osteoarthritis and inflammatory arthritis PJI cases matched 3:1, respectively, by age, sex, and culture status. Clinical characteristics were evaluated using the Fisher exact test, χ 2 test, Student t test, and Mann-Whitney U test where appropriate. Results : A total of 807 PJI cases were identified (36 inflammatory arthritis and 771 osteoarthritis cases). Patients with inflammatory arthritis presented younger, had a higher Charlson Comorbidity Index, more frequently used glucocorticoids, were more likely women, and had a higher proportion of culture-negative PJI compared with osteoarthritis patients. Of the 88 inflammatory arthritis cases reviewed for histopathology, a higher proportion of culture-positive than culture-negative PJI cases had >10 polymorphonuclear leucocytes per high-power field and met Musculoskeletal Infection Society criteria but presented with less chronic inflammation. Conclusions : This retrospective prognostic study suggests that culture-negative PJI may be more frequent in patients with inflammatory arthritis than in those with osteoarthritis. Chronic infections, antibiotic use, or misdiagnosis may be contributing factors to unclear PJI diagnoses among culture-negative cases. This preliminary work supports the need for further studies to assess the differences in clinical features between culture-negative and culture-positive PJI in patients with inflammatory arthritis and the ability of biological diagnostic markers to discriminate between them in this population., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Peter Sculco, MD, reports relationships with EOS Imaging, Intellijoint Surgical, and Lima Corporate. Laura Donlin, PhD, reports relationships with Karius, Inc, and Stryker. Linda Russell, MD, reports a relationship with the Arthritis Foundation. Mark Figgie, MD, reports relationships with HS2, Insight, Lima, Mekanika, and Wishbone. Susan M Goodman, MD, reports relationships with Novartis and UCB. The other authors declare no potential conflicts of interest., (© The Author(s) 2023.)

Osteoarticular mycoses are chronic debilitating infections that require extended courses of antifungal therapy and may warrant expert surgical intervention. As there has been no comprehensive review of these diseases, the International Consortium for Osteoarticular Mycoses prepared a definitive treatise for this important class of infections. Among the etiologies of osteoarticular mycoses are Candida spp., Aspergillus spp., Mucorales, dematiaceous fungi, non-Aspergillus hyaline molds, and endemic mycoses, including those caused by Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides species. This review analyzes the history, epidemiology, pathogenesis, clinical manifestations, diagnostic approaches, inflammatory biomarkers, diagnostic imaging modalities, treatments, and outcomes of osteomyelitis and septic arthritis caused by these organisms. Candida osteomyelitis and Candida arthritis are associated with greater events of hematogenous dissemination than those of most other osteoarticular mycoses. Traumatic inoculation is more commonly associated with osteoarticular mycoses caused by Aspergillus and non-Aspergillus molds. Synovial fluid cultures are highly sensitive in the detection of Candida and Aspergillus arthritis. Relapsed infection, particularly in Candida arthritis, may develop in relation to an inadequate duration of therapy. Overall mortality reflects survival from disseminated infection and underlying host factors.

Introduction : The most common complication following transcutaneous osseointegration for amputees is infection. Although an obvious source of contamination is the permanent stoma, operative site contamination at the time of implantation may be an additional source. This study investigates the impact of unexpected positive intraoperative cultures (UPIC) on postoperative infection. Methods : Charts were reviewed for 8 patients with UPIC and 22 patients with negative intraoperative cultures (NIC) who had at least 1 year of post-osseointegration follow-up. All patients had 24 h of routine postoperative antibiotic prophylaxis, with UPIC receiving additional antibiotics guided by culture results. The main outcome measure was postoperative infection intervention, which was graded as (0) none, (1) antibiotics unrelated to the initial surgery, (2) operative debridement with implant retention, or (3) implant removal. Results : The UPIC vs. NIC rate of infection management was as follows: Grade 0, 6/8 = 75 % vs. 14/22 = 64 %, p = 0.682; Grade 1, 2/8 = 25 % vs. 8/22 = 36.4 % (Fisher's p = 0.682); Grade 2, 1/8 = 12.5 % vs. 0/22 = 0 % (Fisher's p = 0.267); Grade 3, 0/8 = 0 % vs. 1/22 = 4.5 % (Fisher's p = 1.000). No differences were statistically significant. Conclusions : UPIC at index osseointegration, managed with directed postoperative antibiotics, does not appear to increase the risk of additional infection management. The therapeutic benefit of providing additional directed antibiotics versus no additional antibiotics following UPIC is unknown and did not appear to increase the risk of other adverse outcomes in our cohort., Competing Interests: The contact author has declared that neither they nor their co-authors have any competing interests., (Copyright: © 2022 Jason S. Hoellwarth et al.)

There has been increasing interest in the use of a synthetic absorbable calcium sulfate (CaSO 4 ) for local antibiotic delivery in orthopaedic infections. The purpose of this study was to quantify elution kinetics of six antibiotics (amikacin, meropenem, fosfomycin, minocycline, cefazolin, and dalbavancin) from a clinically relevant CaSO 4 bead model and compare elution and antimicrobial activity to the current clinical gold standards: vancomycin and tobramycin. Antibiotic-loaded synthetic CaSO 4 beads were immersed in phosphate buffered saline and incubated at 37°C. Eluent was harvested at eight time points over 28 days. Antibiotic concentrations were measured by high performance liquid chromatography to quantify elution rates. CaSO 4 beads demonstrated burst release kinetics. Dalbavancin, cefazolin, and minocycline all demonstrated similar elution profiles to vancomycin. Amikacin and meropenem demonstrated favorable elution profiles and durations of above-minimum inhibitory concentration when compared to tobramycin. Clinical Significance: This study provides important novel data regarding the utility of amikacin, meropenem and dalbavancin as alternative choices to place in CaSO 4 carriers when treating orthopaedic infections., (© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Background: An intra-articular infection after anterior cruciate ligament (ACL) reconstruction (ACLR) is a rare complication but one with potentially devastating consequences. The rare nature of this complication raises difficulties in detecting risk factors associated with it and with worse outcomes after one has occurred., Purpose: To (1) evaluate the association between an infection after ACLR and potential risk factors in a large single-center cohort of patients who had undergone ACLR and (2) assess the factors associated with ACL graft retention versus removal., Study Design: Case-control study; Level of evidence, 3., Methods: All ACLR procedures performed at our institution between January 2010 and December 2018 were reviewed; a total of 11,451 procedures were identified. A retrospective medical record review was performed to determine the incidence of infections, patient and procedure characteristics associated with an infection, infection characteristics, incidence of ACL graft retention, and factors associated with the retention versus removal of an ACL graft. Multivariable logistic regression analysis was used to identify potential risk factors for an infection after ACLR., Results: Of the 11,451 ACLR procedures, 48 infections were identified (0.42%). Multivariable logistic regression analysis revealed revision ACLR (odds ratio [OR], 3.13 [95% CI, 1.55-6.32]; P = .001) and younger age (OR, 1.06 [95% CI, 1.02-1.10]; P = .001) as risk factors for an infection. Compared with bone-patellar tendon-bone autografts, both hamstring tendon autografts (OR, 4.39 [95% CI, 2.15-8.96]; P < .001) and allografts (OR, 5.27 [95% CI, 1.81-15.35]; P = .002) were independently associated with an increased risk of infections. Overall, 15 ACL grafts were removed (31.3%). No statistically significant differences besides the number of irrigation and debridement procedures were found for retained versus removed grafts, although some trends were identified ( P = .054)., Conclusion: In a large single-center cohort of patients who had undergone ACLR and those with an infection after ACLR, patients with revision cases and younger patients were found to have a higher incidence of infection. The use of bone-patellar tendon-bone autografts was found to be associated with the lowest risk of infection after ACLR compared with both hamstring tendon autografts and allografts. Larger cohorts with a larger number of infection cases are needed to determine the factors associated with graft retention versus removal.

Background: The impact of previous SARS-CoV-2 infection on the morbidity of elective total joint arthroplasty (TJA) is not fully understood. This study reports on the association between previous COVID-19 disease, hospital length of stay (LOS), and in-hospital complications after elective primary TJA., Methods: Demographics, comorbidities, LOS, and in-hospital complications of consecutive 340 patients with a history of COVID-19 were compared with those of 5014 patients without a history of COVID-19 undergoing TJA. History of COVID-19 was defined as a positive IgG antibody test for SARS-CoV-2 before surgery. All patients were given both antibody and polymerase chain reaction tests before surgery., Results: Patients with a history of COVID-19 were more likely to be obese (43.8% vs 32.4%, P < .001), Black (15.6% vs 6.8%, P < .001), or Hispanic (8.5% vs 5.4%, P  = .028) than patients without a history of COVID-19. COVID-19 treatment was reported by 6.8% of patients with a history of COVID-19. Patients with a history of COVID-19 did not have a significantly longer median LOS after controlling for other factors (for hip replacements, median 2.9 h longer, 95% confidence interval = -2.0 to 7.8, P  = .240; for knee replacements, median 4.1 h longer, 95% confidence interval = -2.4 to 10.5, P  = .214), but a higher percentage were discharged to a post-acute care facility (4.7% vs 1.9%, P  = .001). There was no significant difference in in-hospital complication rates between the 2 groups (0/340 = 0.0% vs 22/5014 = 0.44%, P  = .221)., Conclusions: We do not find differences in LOS or in-hospital complications between the 2 groups. However, more work is needed to confirm these findings, particularly for patients with a history of more severe COVID-19., Level of Evidence: II., (© 2022 Published by Elsevier Inc. on behalf of The American Association of Hip and Knee Surgeons.)

Background: Amikacin, meropenem, minocycline, and fosfomycin have potential clinical utility for orthopaedic infections; however, their suitability for use in polymethylmethacrylate (PMMA) is poorly understood. The purpose of this study was (1) to quantify the thermal stability of these antibiotics at clinically relevant temperatures and (2) to determine the elution pharmacodynamics of these alternative antibiotics in vitro from PMMA beads of different sizes., Methods: Polymerization temperatures of 10-mm PMMA beads were measured over time to generate a simulated heating curve. Aqueous solutions of tobramycin, amikacin, meropenem, minocycline, and fosfomycin were subjected to the temperature curves, followed by incubation at 37°C. Minimum inhibitory concentrations of each antibiotic were evaluated against Staphylococcus aureus, Escherichia coli, and Acinetobacter baumannii. High-dose 4.5-mm, 6-mm, and 10-mm antibiotic-laden PMMA beads (10% antibiotic by weight) were submerged individually in a phosphate-buffered saline solution and incubated at 37°C. Antibiotic elution was determined with use of high-performance liquid chromatography with mass spectrometry., Results: Tobramycin, amikacin, and fosfomycin demonstrated thermal stability and maintained antimicrobial activity for 28 days. Minocycline and meropenem lost antimicrobial activity against all 3 organisms after 48 hours and 7 days, respectively. Elution concentrations, rates, and cumulative drug mass for tobramycin, amikacin, and meropenem were orders of magnitude higher than minocycline and fosfomycin at each time point., Conclusions: This study identified notable differences in thermal stability and elution among antibiotics used to treat infections. Amikacin exhibited activity similarly to tobramycin. Meropenem demonstrated favorable elution kinetics and thermal stability in the initial 7-day period., Clinical Relevance: Amikacin and meropenem show pharmacologic promise as potential acceptable alternatives for local delivery in PMMA for treatment of orthopaedic infections. Further work to establish clinical relevance and utility is needed., Competing Interests: Disclosure: This publication was supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) under award number T32 AR007281. 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 (http://links.lww.com/JBJS/G467)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Over 1 million Americans undergo joint replacement each year, and approximately 1 in 75 will incur a periprosthetic joint infection. Effective treatment necessitates pathogen identification, yet standard-of-care cultures fail to detect organisms in 10% to 20% of cases and require invasive sampling. We hypothesized that cell-free DNA (cfDNA) fragments from microorganisms in a periprosthetic joint infection can be found in the bloodstream and utilized to accurately identify pathogens via next-generation sequencing., Methods: In this prospective observational study performed at a musculoskeletal specialty hospital in the U.S., we enrolled 53 adults with validated hip or knee periprosthetic joint infections. Participants had peripheral blood drawn immediately prior to surgical treatment. Microbial cfDNA from plasma was sequenced and aligned to a genome database with >1,000 microbial species. Intraoperative tissue and synovial fluid cultures were performed per the standard of care. The primary outcome was accuracy in organism identification with use of blood cfDNA sequencing, as measured by agreement with tissue-culture results., Results: Intraoperative and preoperative joint cultures identified an organism in 46 (87%) of 53 patients. Microbial cfDNA sequencing identified the joint pathogen in 35 cases, including 4 of 7 culture-negative cases (57%). Thus, as an adjunct to cultures, cfDNA sequencing increased pathogen detection from 87% to 94%. The median time to species identification for cases with genus-only culture results was 3 days less than standard-of-care methods. Circulating cfDNA sequencing in 14 cases detected additional microorganisms not grown in cultures. At postoperative encounters, cfDNA sequencing demonstrated no detection or reduced levels of the infectious pathogen., Conclusions: Microbial cfDNA from pathogens causing local periprosthetic joint infections can be detected in peripheral blood. These circulating biomarkers can be sequenced from noninvasive venipuncture, providing a novel source for joint pathogen identification. Further development as an adjunct to tissue cultures holds promise to increase the number of cases with accurate pathogen identification and improve time-to-speciation. This test may also offer a novel method to monitor infection clearance during the treatment period., Level of Evidence: Diagnostic Level II. 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/G619)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Periprosthetic infection (PJI) after total knee arthroplasty (TKA) places a significant burden on hospitals. We sought to describe the proportion of patients undergoing revision for PJI at a different hospital within one year of primary TKA and whether patient characteristics or hospital volume were associated with this change., Methods: Medicare data from 2005 to 2014 was retrospectively reviewed using PearlDiver. All patients over 64 years undergoing revision for PJI within one year of primary TKA were stratified by the revision occurring within 90 days. Hospitals were grouped by annual TKA volume as Low (<50), Medium (51-100), High (101-200), and Very High (>200). Associations of patient characteristics and hospital volume with revision at a different hospital were assessed using Chi-squared tests and Somers' D., Results: Of 8,337 patients undergoing revision within 90 days of TKA, 1,370 (16%) were revised at a different hospital. Changing hospitals was associated with having primary TKA at a lower volume hospital (24% for low, 15% medium, 12% high, and 12% very high; P < 0.001). Of 7,608 patients undergoing revision between 91 and 365 days, 1,110 (15%) were revised at a different hospital. Changing hospitals was associated with having primary TKA at a lower volume hospital (26% for low, 14% medium, 10% high, and 9% very high; P < 0.001). Changing hospitals was not associated with sex or age., Conclusion: Patients frequently undergo revision for PJI at a different hospital, even within 90 days of TKA. Further research is needed to understand these implications of this care pathway shift., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The concordance between preoperative synovial fluid culture and multiple intraoperative tissue cultures for identifying pathogenic microorganisms in periprosthetic joint infection (PJI) remains unknown. Our aim is to determine the diagnostic performance of synovial fluid culture for early organism identification., Methods: A total of 363 patients who met Musculoskeletal Infection Society criteria for PJI following primary total joint arthroplasty were identified from a retrospective joint infection database. Inclusion criteria required a positive preoperative intra-articular synovial fluid sample within 90 days of intraoperative tissue culture(s) at revision surgery. Concordance was defined as matching organism(s) in aspirate and intraoperative specimens., Results: Concordance was identified in 279 (76.8%) patients with similar rates among total hip arthroplasties (77.2%) and total knee arthroplasties (76.4%, P = .86). Culture discordance occurred in 84 (23.1%) patients; 37 (10.2%) had no intraoperative culture growth and 33 (90.1%) were polymicrobial. Monomicrobial Staphylococcal PJI cases had high sensitivity (0.96, 95% confidence interval [CI] 0.92-0.98) and specificity (0.85, 95% CI 0.80-0.90). Polymicrobial infections had the lowest sensitivity (0.06, 95% CI 0.01-0.19)., Conclusion: Aspiration culture has favorable sensitivity and specificity when compared to tissue culture for identifying the majority of PJI organisms. Clinicians can guide surgical treatment and postoperative antibiotics based on monomicrobial aspiration results, but they should strongly consider collecting multiple tissue cultures to maximize the chance of identifying an underlying polymicrobial PJI., Level of Evidence: Level III., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Debridement, antibiotics, and implant retention (DAIR) failure remains high for total hip and knee arthroplasty periprosthetic joint infection (PJI). We sought to determine the predictive value of the CRIME80 and KLIC for failure of DAIR in acute hematogenous (AH) and acute postoperative (AP) PJIs, respectively., Methods: We identified 134 patients who underwent DAIR for AH PJI with <4 weeks of symptoms after index arthroplasty and 122 patients who underwent DAIR for AP PJI <90 days from index. In the AH group, 15 patients (11%) failed at 90 days and overall, 33 (25%) had failed by 2 years. In the AP group, 39 (32%) failed at 90 days and overall, 52 (43%) failed by 2 years. Logistic regression models were used to determine the area under the curve (AUC) to establish thresholds using the Youden index., Results: For the AP cohort, AUCs were below 0.66 for KLIC, Charlson comorbidity index, Elixhauser comorbidity index, and McPherson host grade. For the AH cohort, 90-day AUCs were 0.70 for CRIME80 and below 0.66 for Charlson comorbidity index, Elixhauser comorbidity index, and McPherson host grade. In multivariate analysis controlling for age, sex, and body mass index, the CRIME80 AUC improved to 0.77 at 90 days., Conclusion: To the authors' knowledge, this study represents the first external validation of the KLIC and CRIME80 for predicting DAIR failure in a North American population. The results indicate that alternative methods for predicting DAIR failure at 90 days and 2 years for acute PJI are needed., Level of Evidence: Prognostic III., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: We measured the seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) immunoglobulin G (IgG) antibodies among surgeons and anesthesiologists and associated antibody status with coronavirus disease 2019 (COVID-19) clinical illness., Methods: A cross-sectional study of SARS-CoV-2 IgG seroprevalence with a survey assessing demographics, SARS-CoV-2 exposure risk, and COVID-19 illness. The primary outcome was the period prevalence of SARS-CoV-2 IgG antibodies associated with COVID-19 illness., Results: One hundred forty three surgeons and anesthesiologists completed both serology and survey testing. We found no significant relationships between antibody status and clinical role (anesthesiologist, surgeon), mode of commuting to work, other practice settings, or place of residence. SARS-CoV-2 IgG seroprevalence was 9.8%. Positive IgG status was highly correlated with presence of symptoms of COVID-19 illness., Conclusions: These results suggest the relative safety of surgeons and anesthesiologists where personal protective equipment (PPE) is available and infection control protocols are implemented., Competing Interests: Conflict of Interest: None declared., (Copyright © 2021 American College of Occupational and Environmental Medicine.)

Competing Interests: Conflict of InterestMeghan A. Kirksey, MD, PhD; Elaine I. Yang, MD; Mausam Kuvadia, MD; and Andy O. Miller, MD, declare that they have no conflicts of interest.

Background: COVID-19, the illness caused by the novel coronavirus, SARS-CoV-2, has sickened millions and killed hundreds of thousands as of June 2020. New York City was affected gravely. Our hospital, a specialty orthopedic hospital unaccustomed to large volumes of patients with life-threatening respiratory infections, underwent rapid adaptation to care for COVID-19 patients in response to emergency surge conditions at neighboring hospitals., Purposes: We sought to determine the attributes, pharmacologic and other treatments, and clinical course in the cohort of patients with COVID-19 who were admitted to our hospital at the height of the pandemic in April 2020 in New York City., Methods: We conducted a retrospective observational cohort study of all patients admitted between April 1 and April 21, 2020, who had a diagnosis of COVID-19. Data were gathered from the electronic health record and by manual chart abstraction., Results: Of the 148 patients admitted with COVID-19 (mean age, 62 years), ten patients died. There were no deaths among non-critically ill patients transferred from other hospitals, while 26% of those with critical illness died. A subset of COVID-19 patients was admitted for orthopedic and medical conditions other than COVID-19, and some of these patients required intensive care and ventilatory support., Conclusion: Professional and organizational flexibility during pandemic conditions allowed a specialty orthopedic hospital to provide excellent care in a global public health emergency., Competing Interests: Conflict of InterestAndy O. Miller, MD, Milan Kapadia, BS, Meghan A. Kirksey, MD, PhD, Milan Sandhu, MS, Deanna Jannat-Khah, DrPH, Trang Bui, MD, MPH, K. Keely Boyle, MD, Alexandra Krez, BA, Linda Russell, MD, Jennifer O’Neill, DNP, APN, NEA-BC, Emily M. Stein, MD, MS, Michael W. Henry, MD, and Vinicius C. Antao, MD, PhD, declare that they have no conflicts of interest. Emily M. Stein, MD, MS, reports grants from Novartis and Radius, outside the submitted work. Douglas E. Padgett, MD, reports personal fees from DJO Global, PSI LLC, and Tangen, outside the submitted work., (© Hospital for Special Surgery 2020.)

Background: Reported clinical outcomes have varied for debridement, antibiotics, and implant retention (DAIR) and little is known regarding trends in utilization. We sought to evaluate the rate of DAIR utilization for total knee arthroplasty (TKA) and total hip arthroplasty (THA) periprosthetic joint infection (PJI) over a decade and clinical factors associated with these trends., Methods: A retrospective study of primary TKAs and THAs was performed using Medicare data from 2005 to 2014 using the PearlDiver database platform. Current Procedural Technology and International Classification of Diseases Ninth Edition codes identified patients who underwent a surgical revision for PJI, whether revision was a DAIR, as well as associated clinical factors including timing from index arthroplasty., Results: The proportion of revision TKAs and THAs performed using DAIR was 27% and 12% across all years, respectively. This proportion varied by year for TKAs and THAs with a linear trend toward increasing relative use of DAIR estimated at 1.4% and 0.9% per year (P < .001; P < .001). DAIR for TKA and THA performed within 90 days increased at a faster rate, 3.4% and 2.1% per year (P < .001; P < .001). Trends over time in TKA DAIRs showed an association with Elixhauser Comorbidity Index (ECI), 0-5 group increasing at 2.0% per year (P = .03) and patients >85 years (P = .04)., Conclusion: The proportion of revision arthroplasty cases for PJI managed with DAIR has been increasing over time in the United States, with the most substantial increase seen <90 days from index arthroplasty. Age, gender, and ECI had a minimal association with this trend, except in the TKA population >85 years and in those with a very low ECI score., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Periprosthetic joint infection (PJI) after unicompartmental knee arthroplasty (UKA) is a devastating but poorly understood complication, with a paucity of published data regarding treatment and outcomes. This study analyzes the largest cohort of UKA PJIs to date comparing treatment outcome, septic and aseptic reoperation rates, and risk factors for treatment failure., Methods: Twenty-one UKAs in 21 patients treated for PJI, as defined by Musculoskeletal Infection Society criteria, were retrospectively reviewed. Minimum and mean follow-up was 1 and 3.5 years, respectively. Fourteen (67%) patients had acute postoperative PJIs. Surgical treatment included 16 debridement, antibiotics, and implant retentions (DAIRs) (76%), 4 two-stage revisions (19%), and 1 one-stage revision (5%). Twenty (95%) PJIs were culture positive with Staphylococcus species identified in 15 cases (71%)., Results: Survivorship free from reoperation for infection at 1 year was 76% (95% confidence interval, 58%-93%). Overall survival from all-cause reoperation was 57% (95% confidence interval, 27%-87%) at 5 years. Two additional patients (10%) underwent aseptic revision total knee arthroplasty for lateral compartment degeneration 1 year after DAIR and tibial aseptic loosening 2.5 years after 2-stage revision. All patients who initially failed PJI UKA treatment presented with acute postoperative PJIs (5 of 14; 36%)., Conclusion: Survivorship free from persistent PJI at 1 year is low at 76% but is consistent with similar reports of DAIRs for total knee arthroplasties. Furthermore, there is low survivorship free from all-cause reoperation of 71% and 57% at 2 and 5 years, respectively. Surgeons should be aware of these poorer outcomes and consider treating UKA PJI early and aggressively., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: A number of clinical trials have been conducted, assessing the role of long-term (>1 year) suppressive antibiotic treatment (SAT) combined with Debridement, Antibiotics, and Implant Retention (DAIR) for the management of peri-prosthetic joint infection (PJI). However, no systematic review of the literature has been published to date to evaluate complications associated with long-term antibiotic treatment and overall survivorship free from re-operation and revision for infection after DAIR for total hip and total knee PJI., Methods: The US National Library of Medicine (PubMed/MEDLINE), EMBASE, and the Cochrane Database of Systematic Reviews were queried for publications from January 1980 to December 2018 utilizing keywords pertinent to total knee arthroplasty, total hip arthroplasty, PJI, and antibiotic suppression., Results: Overall, 7 articles of low quality (level III or IV) were included in this analysis. The studies included in this systematic review included 437 cases of PJI treated surgically with DAIR and then with SAT. The overall mean infection-free rate of SAT following DAIR was 75% (318/424 patients), while the all-cause re-operation rate was 6.7%. Overall, the mean rate of adverse effects associated with long-term antibiotic use was 15.4% and the mean rate of adverse effects leading to discontinuation of SAT was 4.3%. There was no study to show significant differences between acute (either post-operative or hematogenous, with onset of symptoms ≤4 weeks) and chronic (onset of symptoms >4 weeks) infections and failure rates of DAIR with SAT. The literature is inconclusive on the influence of anatomic location (hip vs knee) as well as microorganism on the success rate of DAIR with SAT., Conclusion: The results of this systematic review demonstrate that there is still only low-quality evidence regarding the therapeutic effect of DAIR combined with SAT, which is not enough to draw definitive conclusions. Furthermore, high-quality prospective studies are needed to better understand SAT's efficacy and safety in a controlled fashion. Although discontinuation of antibiotic treatment due to side effects was found to be low, the high rates of adverse effects noted after DAIR with SAT demonstrate the underlying frailty and complexity of many patients with PJI, and the imperfect therapies available. Although Staphylococcus aureus appears to be a risk factor for increased risk of SAT failure, there are not enough data to establish which patients would benefit most from DAIR with post-operative SAT., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background : The role of daptomycin, a potent, safe, convenient anti-staphylococcal antibiotic, in treatment of prosthetic joint infection (PJI) is unclear. We evaluated our experience with the largest cohort of patients with staphylococcal PJI managed with daptomycin. Methods : A cohort of staphylococcal hip and knee PJI treated with daptomycin was identified by hospital records from 2009 to 2016. All cases met Musculoskeletal Infection Society International Consensus criteria for PJI. The primary endpoint was 2 year prosthesis retention. Univariate analyses and regression statistics were calculated. Results : 341 patients with staphylococcal PJI were analyzed. 154 two-stages (77%) and 74 DAIR procedures (52%) met criteria for treatment success at 2 years. 77 patients were treated with daptomycin, of which 34 two-stages (68%) and 15 DAIRs (56%) achieved treatment success. Pairwise and regression analysis found no association between treatment success and daptomycin use. Organism (DAIR only) and Charlson Comorbidity Index scores (DAIR and two-stage) were significantly associated with treatment outcome. Six daptomycin patients (7.8%) had adverse side effects. Discussion : Daptomycin fared no better or worse than comparable antibiotics in a retrospective cohort of staphylococcal hip and knee PJI patients, regardless of surgical strategy. Conclusion : The convenient dosing, safety, and potency of daptomycin make it an attractive antibiotic for staphylococcal PJI. However, these advantages must be weighed against higher costs and rare, but serious side effects., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Introduction: To confirm the success of our limb salvage treatment protocol and determine what factors are predictive of success versus failure in limb salvage techniques for patients with chronic osteomyelitis of the tibia and ankle. Methods: Retrospective case series analyzing factors and outcomes in patients who underwent limb salvage techniques for chronic osteomyelitis of tibia or ankle. Main outcome measurements included infection controlled without the need for amputation or chronic antibiotic suppression and union of infected non-unions. Results: Mean follow-up was 3.9 years. Out of the sixty-seven patients (mean age: 51.4 years) treated for chronic osteomyelitis, fifty-four had an associated non-union. Sixty-one patients (91.0%) had their infection controlled by limb salvage. Five ultimately required amputation and one remained on daily chronic antibiotics. Diabetics complicated with neuropathy and increasing numbers of limb salvage surgeries were associated with a significantly higher failure rate. Forty-eight out of fifty-four patients (88.9%) also had successful healing of their infected non-union. Diabetes and need for more limb salvage surgeries were also found to have a significantly higher failure rate. Conclusions: Limb salvage is a reliable and successful treatment for patients with chronic osteomyelitis and infected non-unions of the lower extremities. Diabetic neuropathy is a risk factor that impedes success. Level of Evidence: Prognostic Level IV., Competing Interests: Competing Interests: SRR is a paid consultant for Smith & Nephew, NuVasive and Stryker. ATF is a paid consultant for Smith & Nephew, NuVasive and Synthes. For the remaining authors, none were declared., (© The author(s).)

In 2018, Inabathula et al. published the results of a historical control study examining 90-day peri-prosthetic joint infection (PJI) rates at a single center before and after the institution of an extended post-operative oral antibiotic protocol for high-risk total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients. In the study, "Extended Oral Antibiotic Prophylaxis in High-Risk Patients Substantially Reduces Primary Total Hip and Knee Arthroplasty 90-Day Infection Rate" ( J Bone Joint Surg Am . 2018;100[24]:2103-2109), the authors considered any one of several patient-related criteria-including diabetes, a body mass index of 35 kg/m 2 or higher, or active smoking-as sufficient to designate a patient "high risk" for PJI. Before the extended antibiotic therapy protocol was instituted, PJI rates for primary THA and TKA in the high-risk subgroup were 4.3% and 2.1%, respectively. After it was instituted, the respective rates dropped to 1.1% and 0.4%, comparable to those seen in the non-high-risk patients treated using standard peri-operative prophylaxis. After adjusting for patient factors, regression analysis showed that high-risk patients receiving only peri-operative antibiotics were more likely to develop PJI than high-risk patients receiving the extended antibiotic protocol. Although these results suggest possible benefits of extended antibiotic prophylaxis in arthroplasty, methodologic limitations and inadequate discussion of potential drawbacks of widespread adoption of such protocols limit the impact of the findings. Future research is warranted to more narrowly define risk factors for PJI and to demonstrate the safety and efficacy of extended antibiotics in reducing the long-term burden of PJI., Competing Interests: Conflict of InterestChristopher J. DeFrancesco, MD; Michael C. Fu, MD, MHS; Cynthia A. Kahlenberg, MD; and Andy O. Miller, MD, declare that they have no conflicts of interest. Mathias P. Bostrom, MD, reports personal fees from Smith & Nephew, outside the submitted work., (© Hospital for Special Surgery 2019.)

Background: Rheumatoid arthritis patients are at increased risk for periprosthetic joint infection after arthroplasty. The reason is multifactorial. Nasal colonization with Staphylococcus aureus is a modifiable risk factor; carriage rates in RA patients are unknown. The goal of this study is to determine the S aureus nasal carriage rates of RA patients on biologics, RA patients on traditional disease-modifying anti-rheumatic drugs (DMARDs), and osteoarthritis., Methods: Consecutive patients with RA on biologics (±DMARDs), RA on non-biologic DMARDs, or OA were prospectively enrolled from April 2017 to May 2018. One hundred twenty-three patients were determined necessary per group to show a difference in carriage rates. Patients underwent a nasal swab and answered questions to identify additional risk factors. S aureus positive swabs were further categorized using spa typing. Logistic regression evaluated the association with S aureus colonization between the groups after controlling for known risk factors., Results: RA patients on biologics, 70% of whom were on DMARDs, had statistically significant increase in S aureus colonization (37%) compared to RA on DMARDs alone (24%), or OA (20%) (P = .01 overall). After controlling for glucocorticoids, antibiotic use, recent hospitalization, and diabetes, RA on biologics had a significant increased risk of S aureus nasal colonization (Odds ratio 1.80, 95% confidence interval 1.00-3.22, P = .047)., Conclusion: S aureus colonization risk was increased for RA on biologics compared to RA not on biologics and OA. Nasal S aureus carriage increases the risk of surgical site infection; this modifiable risk factor should be addressed prior to total joint arthroplasty for this higher risk patient group., (Copyright © 2019 Elsevier Inc. All rights reserved.)

As a result of advances in surgery, anesthesiology, and perioperative care, patients of more advanced age and medical complexity are now considered suitable candidates for surgical intervention. Rheumatologists, though frequently called upon to advise their patient in the surgical domain, may not be fully cognizant of the principles underlying medical consultation and therapy in perioperative setting. This paper provides an approach for guiding such medical care with a particular focus on the concerns pertinent to patient suffering from a chronic rheumatic disease., (Copyright © 2019. Published by Elsevier Ltd.)

Staphylococcus aureus is an opportunistic pathogen that causes a range of serious infections associated with significant morbidity, by strains increasingly resistant to antibiotics. However, to date all candidate vaccines have failed to induce protective immune responses in humans. We need a more comprehensive understanding of the antigenic targets important in the context of human infection. To investigate infection-associated immune responses, patients were sampled at initial presentation and during convalescence from three types of clinical infection; skin and soft tissue infection (SSTI), prosthetic joint infection (PJI) and pediatric hematogenous osteomyelitis (PHO). Reactivity of serum IgG was tested with an array of recombinant proteins, representing over 2,652 in-vitro-translated open reading frames (ORFs) from a community-acquired methicillin-resistant S. aureus USA300 strain. High-level reactivity was demonstrated for 104 proteins with serum IgG in all patient samples. Overall, high-level IgG-reactivity was most commonly directed against a subset of secreted proteins. Although based on limited surveys, we found subsets of S. aureus proteins with differential reactivity with serum samples from patients with different clinical syndromes. Together, our studies have revealed a hierarchy within the diverse proteins of the S. aureus "immunome", which will help to advance efforts to develop protective immunotherapeutic agents.

Staphylococcus aureus is a Gram-positive opportunistic pathogen that causes superficial and invasive infections in the hospital and community. High mortality from infection emphasizes the need for improved methods for prevention and treatment. Although S. aureus possesses an arsenal of virulence factors that contribute to evasion of host defenses, few studies have examined long-term humoral and B-cell responses. Adults with acute-phase skin and soft tissue infections were recruited; blood samples were obtained; and S. aureus isolates, including methicillin-resistant strains, were subjected to genomic sequence analysis. In comparisons of acute-phase sera with convalescent-phase sera, a minority (37.5%) of patients displayed 2-fold or greater increases in antibody titers against three or more S. aureus antigens, whereas nearly half exhibited no changes, despite the presence of toxin genes in most infecting strains. Moreover, enhanced antibody responses waned over time, which could reflect a defect in B-cell memory or long-lived plasma cells. However, memory B cells reactive with a range of S. aureus antigens were prevalent at both acute-phase and convalescent-phase time points. While some memory B cells exhibited toxin-specific binding, those cross-reactive with structurally related leucocidin subunits were dominant across patients, suggesting the targeting of conserved epitopes. Memory B-cell reactivity correlated with serum antibody levels for selected S. aureus exotoxins, suggesting a relationship between the cellular and humoral compartments. Overall, although there was no global defect in the representation of anti- S. aureus memory B cells, there was evidence of restrictions in the range of epitopes recognized, which may suggest potential therapeutic approaches for augmenting host defenses. IMPORTANCE The contribution of B-cell memory and long-term antibody responses to host defenses against S. aureus exotoxins remains poorly understood. Our studies confirmed that infection did not commonly lead to enhanced long-term humoral responses. Whereas circulating memory B cells against S. aureus secreted exotoxins were prevalent, they were dominated by cross-reactivity with structurally related leucocidin subunits, consistent with recognition of conserved epitopes. These findings also provide the first evidence of a relationship between the reactivity of antistaphylococcal circulating memory B cells and serum antibody levels. In general, infection was not associated with a global defect in B-cell memory for S. aureus secreted factors, and responses were highly dominated by cross-reactivity to structurally related exotoxins, which arguably may alone be suboptimal in providing host defenses. Our studies illuminate aspects of the S. aureus- host relationship that may better inform strategies for the development of an effective protective vaccine., (Copyright © 2018 Pelzek et al.)

Objective: To evaluate the outcomes of a single-stage surgical protocol to treat a presumed aseptic long-bone nonunion with positive intraoperative cultures obtained at the time of surgery., Design: Retrospective comparative series., Setting: Orthopaedic specialty hospital., Patients and Methods: We retrospectively identified 77 patients with long-bone nonunions thought to be aseptic preoperatively, which grew bacteria from cultures obtained at the time of index nonunion surgery., Intervention: Fifty (65%) patients underwent open debridement of the nonunion site followed by surgical stabilization through plates and screws. Twenty-seven (35%) patients underwent exchange nailing with canal reamings used for cultures., Main Outcome Measurement: Rate of radiographic union, time to clinical and radiographic union, nonunion rate after index nonunion surgery, and final union rate after revision procedures., Results: Osseous union after the index nonunion surgery was achieved in 84% of the patients (65 of 77). Time to clinical union was 6.3 months (range, 1-24 months), and time to radiographic union was 7.4 months (range, 2-24 months). Eighteen percent (14 of 77 patients) did not heal after the index nonunion surgery and required additional surgeries. The final union rate after revision surgery was 99% (76 of 77 patients)., Conclusions: Eighty-four percent of presumed aseptic nonunions of long-bone fractures with positive intraoperative cultures fully healed after a single-stage surgical protocol and long-term antibiotic when appropriate. When patients are diagnosed with a subclinical infected nonunion, they should be counseled about the higher likelihood of reoperation, but in most cases can expect excellent union rates after 1 additional surgery., Level of Evidence: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Background: The optimal type, characteristics, and success rates of articulating antibiotic spacers used during total knee arthroplasty (TKA) periprosthetic joint infection (PJI) have not been well defined in a single series. We sought to (1) determine the success rate for three unique spacer constructs and (2) evaluate any microbiological, surgical, or patient characteristics that would influence the success rate., Methods: We retrospectively reviewed patients who underwent a two-stage exchange for a TKA PJI with a prefabricated spacer (PREFAB), home-made mold (MOLD), or autoclaved femoral component (AUTOCL). Patient demographics, microbiology data, amount of antibiotic in each spacer construct, postoperative course, and infection cure outcomes were evaluated., Results: The success rate for being infection free at final follow-up without the need for further reoperation for infection was 82.7% in the PREFAB group, 88.4% in the MOLD group, and 79.4% in the AUTOCL group (p=0.54). There was no clear statistical link between raw quantities of vancomycin and aminoglycoside in the spacer and a successful outcome. The surgeon's own intraoperatively created mold group had the lowest construct cost at a mean $1341.00±889.10 (p<0.0001) per construct, while the commercial cement molds had the highest mean cost at $5439.00±657.80 (p<0.0001)., Conclusions: There was no statistically significant difference in the success rates between the antibiotic spacer types. The surgeon's own intraoperative mold had the least overall associated cost., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The risk of prosthetic joint infection increases with Staphylococcus aureus colonization. The cost-effectiveness of decolonization is controversial. We evaluated cost-effectiveness decolonization protocols in high-risk arthroplasty patients., Methods: An analytical model evaluated risk under 3 protocols: 4 swabs, 2 swabs, and nasal swab alone. These were compared to no-screening and universal decolonization strategies. Cost-effectiveness was evaluated from the hospital, patient, and societal perspective., Results: Under base case conditions, universal decolonization and 4-swab strategies were most effective. The 2-swab and universal decolonization strategy were most cost-effective from patient and societal perspectives. From the hospital perspective, universal decolonization was the dominant strategy (much less costly and more effective)., Conclusion: S aureus decolonization may be cost-effective for reducing prosthetic joint infections in high-risk patients. These results may have important implications for treatment of patients and for cost containment in a bundled payment system., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Propionibacterium acnes ( P. acnes ) has become increasingly recognized as a cause of periprosthetic joint infection (PJI)., Questions/purposes: It is not currently known if the clinical presentation of P. acnes varies depending on the joint being infected., Methods: We retrospectively reviewed patients infected with P. acnes after total hip, knee, and shoulder arthroplasty from two institutions. Patients were classified as having a PJI based on the Musculoskeletal Infection Society criteria and were excluded if they had a polymicrobial culture. Patient demographics, preoperative laboratory values, and microbiology data were analyzed., Results: Eighteen knees, 12 hips, and 35 shoulders with a P. acnes PJI were identified. Median ESR was significantly higher in the knee (38.0 mm/h, IQR 18.0-58.0) and hip (33.5 mm/h, IQR 15.3-60.0) groups compared to the shoulder group (11.0 mm/h, IQR 4.5-30.5). C-reactive protein levels were higher in the knee (2.0 mg/dl, IQR 1.3-8.9) and hip (2.4 mg/dl, IQR 0.8-4.9) groups compared to the shoulder group (0.7 mg/dl, IQR 0.6-1.5). Median synovial fluid WBC was significantly higher in the knee group than shoulder group (19,950 cells/mm 3 , IQR 482-60,063 vs 750 cells/mm 3 , IQR 0-2825, respectively). Peripheral blood WBC levels were similar between groups, as was mean time of P. acnes growth in culture. Clindamycin resistance was present in all groups., Conclusion: The manner in which a patient with P. acnes PJI presents is joint specific. Inflammatory markers were significantly higher in the knee and hip groups compared to the hip and shoulder groups, and long hold anaerobic cultures up to 14 days are necessary to accurately identify this organism.

Background: Pin infection continues to be a nuisance when using definitive external fixation. Prophylactic antibiotic treatment has been proposed in an effort to decrease pin complications., Questions/purposes: We performed a prospective, randomized, single-blinded study to answer the following questions: (1) what was the effect of a 10-day course of oral prophylactic antibiotics administered immediately after external fixation surgery on the incidence of a subsequent pin infection, (2) what was the effect on the severity of a subsequent pin infection, and (3) what was the effect on the timing of a subsequent pin infection?, Methods: Patients were randomized into antibiotic treatment and control groups, and incidence, severity, and time of onset of pin infection were recorded., Results: The incidence of pin infection for the entire cohort during the 90-day observation period was 46/58 (79%) without a statistically significant difference ( p  = 0.106). There was no statistical difference found ( p  = 0.512) in pin infection severity. There was no significant difference in the time of onset of infection between the two groups from the date of surgery ( p  = 0.553)., Conclusions: Our randomized data do not suggest that oral antibiotics alter the incidence, timing, or severity of pin infection. This study does not support the use of prophylactic oral antibiotics in healthy patients.

Fungi are rare but important causes of osteoarticular infections, and can be caused by a wide array of yeasts and molds. Symptoms are often subacute and mimic those of other more common causes of osteoarticular infection, which can lead to substantial delays in treatment. A high index of suspicion is required to establish the diagnosis. The severity of infection depends on the inherent pathogenicity of the fungi, the immune status of the host, the anatomic location of the infection, and whether the infection involves a foreign body. Treatment often involves a combination of surgical debridement and prolonged antifungal therapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Study Design: Single-institution, retrospective case series., Objective: To determine whether the microbiology of deep surgical site infections (SSIs) after spinal fusion surgery for deformity has changed over the last decade at our institution., Summary of Background Data: SSI after pediatric spinal deformity surgery results in significantly increased patient morbidity and health care costs. Although risk factors are multifactorial, prophylactic and treatment antibiotic coverage is based in part on historical epidemiologic data, which may evolve over time., Methods: This study represents a retrospective review of clinical and microbiology records of patients less than 21 years old who underwent spinal deformity surgery at a single institution between 2000 and 2012. Patients were included who underwent index surgery at our institution and developed a deep SSI. Patients with growth-preserving spine constructs were excluded., Results: The overall incidence of deep SSI was 3.6% (39/1094). The incidence of deep SSI following primary surgery was 3.3% (34/1034) and 8.3% (5/60) following revision surgery. The incidence of deep SSI varied by primary diagnosis: idiopathic (1.0%), neuromuscular (14.3%), syndromic (5.3%), congenital (5.7%), and kyphosis (0.0%). The most common inciting pathogens were Staphylococcus epidermidis (26%), methicillin-sensitive Staphylococcus aureus (MSSA, 18%), Propionibacterium acnes (P. acnes; 18%), and Escherichia coli (18%). Sixteen of the 18 (89%) gram-negative infections occurred in neuromuscular patients (P = 0.006). Between 2000 and 2006 and between 2007 and 2012, MSSA occurred in 2/18 (11%) and 5/21 (24%) of cases (P = 0.41), methicillin-resistant S. aureus occurred in 1/18 (6%) and 3/21 (14%) (P = 0.61), and P. acnes occurred in 3/18 (17%) and 4/21 (19%) (P = 1.0)., Conclusion: The epidemiology of deep SSI following spinal fusion for deformity in pediatric patients at our institution has not changed significantly during 13 years. Prophylactic antibiotic coverage for both gram-positive and gram-negative organisms may be indicated for patients with primary neuromuscular diagnoses., Level of Evidence: 4.

Background: Globicatella sanguinis is an uncommon pathogen that may be misdiagnosed as viridans group streptococci. We review the literature of Globicatella and report 2 clinical cases in which catalase-negative Gram-positive cocci resembling viridans group streptococci with elevated minimum inhibitory concentrations (MICs) to ceftriaxone were inconsistently identified phenotypically, with further molecular characterization and ultimate identification of G sanguinis ., Methods: Two clinical strains (from 2 obese women; 1 with a prosthetic hip infection and the other with bacteremia) were analyzed with standard identification methods, followed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry, 16S recombinant ribonucleic acid (rRNA), and sodA polymerase chain reaction (PCR). The existing medical literature on Globicatella also was reviewed., Results: Standard phenotypic methods failed to consistently identify the isolates. 16S PCR yielded sequences that confirmed Globicatella species. sodA sequencing provided species-level identification of G sanguinis . The review of literature reveals G sanguinis as an increasingly reported cause of infections of the urine, meninges, and blood. To our knowledge, this is the first reported case of an orthopedic infection caused by Globicatella sanguinis . A review of the 37 known cases of G sanguinis infection revealed that 83% of patients are female, and 89% are at the extremes of age (<5 or >65 years)., Conclusions: Globicatella sanguinis , an uncommon pathogen with elevated minimum inhibitory concentrations to third-generation cephalosporins, is difficult to identify by phenotypic methods and typically causes infections in females at the extremes of age. It may colonize skin or mucosal surfaces. Advanced molecular techniques utilizing 16S rRNA with sodA PCR accurately identify G sanguinis ., (© The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Propionibacterium acnes is a common cause of upper extremity arthroplasty infection and usually presents in an indolent subacute fashion. It is not well described how total knee arthroplasty (TKA) patients infected with P acnes present., Methods: We retrospectively compared patients undergoing revision TKA for infection from P acnes and methicillin-sensitive Staphylococcal aureus (MSSA) in our institutional infection database. Patients were classified as having a periprosthetic joint infection based on the Musculoskeletal Infection Society criteria and were excluded if they had a polymicrobial culture. Patient demographics, preoperative laboratory values, microbiology data, and synovial fluid white blood cell (WBC) counts were analyzed., Results: Sixteen patients with a P acnes and 30 with an MSSA TKA periprosthetic joint infection were identified. Median erythrocyte sedimentation rate was significantly higher in the MSSA group compared to the P acnes group (56.0 mm/h; interquartile range [IQR], 44.3-72.9 vs 23.0 mm/h; IQR, 18.5-52.0; respectively, P = .03) as were C-reactive protein levels (5.9 mg/dL; IQR, 3.7-26.9 vs 2.0 mg/dL; IQR, 0.5-14.0; respectively, P = .04). WBC count, synovial fluid WBC, and percentage of synovial polymorphonuclear cells were similar between groups. Mean time to culture was 8.3 ± 2.0 days in the P acnes group and 1.8 ± 0.8 days in the MSSA group., Conclusion: P acnes TKA infections are associated with more acute inflammatory symptoms than typically appreciated, and long hold anaerobic cultures up to 14 days are necessary to accurately identify this organism as the causative agent of TKA periprosthetic infection., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Early detection of surgical site infection (SSI) following spinal surgery would allow for prompt treatment and would improve overall outcome, yet early diagnosis is a challenge. Computed tomography (CT) guided aspiration of fluid collections may aid in diagnosis, as its diagnostic utility has previously been demonstrated in the setting of hip SSI, knee SSI, and spontaneous diskitis. There is no literature on its use in post-operative spinal SSIs., Questions/purposes: The current study aims to (1) determine the diagnostic value of CT-guided aspiration in evaluating suspected SSI; (2) identify the characteristics of the clinical presentation that are predictive of SSI; and (3) identify characteristics of the hematologic workup that are predictive of SSI., Methods: Thirty patients who underwent CT-guided aspiration of paraspinal post-operative fluid collections and culture of aspirate fluid over the 6-year period from 2006 to 2011 were retrospectively reviewed. Aspirate fluid culture results were compared to intraoperative cultures, which were used as the "gold standard" for diagnosing SSI. The diagnostic value was evaluated by determining the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of aspirate fluid cultures. Clinical presentation, patient demographics, comorbidities, and laboratory values were reviewed for association with infection risk., Results: Eleven of thirty patients undergoing CT-guided aspiration were subsequently confirmed to have SSI through positive cultures. Wound drainage, wound erythema, elevated ESR, and cloudiness of aspirate fluid were associated with SSI. The sensitivity and specificity of aspirate cultures were 36.4 and 89.5%, respectively, and the respective positive predictive value (PPV) and negative predictive value (NPV) were 66.7 and 70.8%., Conclusions: Cloudy aspirate fluid was highly suggestive of infection, while wound erythema, drainage, and elevated ESR were also suggestive of SSI. CT-guided aspirations are a useful adjunct tool in evaluating for SSI but further studies are necessary before it can be considered a stand-alone diagnostic procedure.

Rapidly growing mycobacteria (RGM) are a rare but treatable cause of prosthetic joint infections. This study reports on two patients comprising three prosthetic joint infections caused by RGM successfully treated at the institution. With removal of the infected prosthetic joint and judicious use of prolonged courses of antibiotics, patients with prosthetic joint infections secondary to RGM can both be cured and retain function of the affected joint. In addition, this study identified 40 additional cases reported during an extensive review of the literature and provide a summary of these cases. These infections can present within days of arthroplasty or can develop only decades after the index surgery. The clinical presentations often mimic those of more routine bacterial prosthetic joint infections.

Background.  Candida arthritis is a debilitating form of deeply invasive candidiasis. However, its epidemiology, clinical manifestations, management, and outcome are not well understood. Methods.  Cases of Candida arthritis were reviewed from 1967 through 2014. Variables included Candida spp in joint and/or adjacent bone, underlying conditions, clinical manifestations, inflammatory biomarkers, diagnostic imaging, management, and outcome. Results.  Among 112 evaluable cases, 62% were males and 36% were pediatric. Median age was 40 years (range, <1-84 years). Most patients (65%) were not pharmacologically immunosuppressed. Polyarticular infection (≥3 joints) occurred in 31% of cases. Clinical manifestations included pain (82%), edema (71%), limited function (39%), and erythema (22%) with knees (75%) and hips (15%) most commonly infected. Median erythrocyte sedimentation rate was 62 mm/hr (10-141) and C reactive protein 26 mg/dL (0.5-95). Synovial fluid median white blood cell count was 27 500/µL (range, 100-220 000/µL) with 90% polymorphonuclear neutrophils (range, 24-98). Adjacent osteomyelitis was present in 30% of cases. Candida albicans constituted 63%, Candida tropicalis 14%, and Candida parapsilosis 11%. Most cases (66%) arose de novo, whereas 34% emerged during antifungal therapy. Osteolysis occurred in 42%, joint-effusion in 31%, and soft tissue extension in 21%. Amphotericin and fluconazole were the most commonly used agents. Surgical interventions included debridement in 25%, irrigation 10%, and drainage 12%. Complete or partial response was achieved in 96% and relapse in 16%. Conclusion.  Candida arthritis mainly emerges as a de novo infection in usually non-immunosuppressed patients with hips and knees being most commonly infected. Localizing symptoms are frequent, and the most common etiologic agents are C albicans, C tropicalis, and C parapsilosis. Management of Candida arthritis remains challenging with a clear risk of relapse, despite antifungal therapy.