Tande, Aaron J.

Abstract: Kimura disease typically presents with painless head and neck swelling in young adults of Asian descent, accompanied by peripheral eosinophilia and elevated serum IgE. We report a case of Kimura disease in a woman in her early 30s presenting with a slowly enlarging epitrochlear mass, diffuse encasement of the median and medial brachial cutaneous nerves, and a concurrent prurigo nodularis-like papular rash affecting all 4 extremities. The diagnosis required over 1 year of investigation and 5 tissue specimens, including 2 nondiagnostic core-needle biopsies, before near total excision was performed. The excision revealed characteristic histopathologic features, including hyperplastic reactive secondary lymphoid follicles with preserved architecture, a marked eosinophilic infiltrate with eosinophilic microabscesses, postcapillary venule proliferation, and patternless stromal fibrosis. Immunohistochemistry demonstrated a raised IgG4:IgG plasma cell ratio of approximately 1:1, with 150–200 IgG4-positive plasma cells per high-power field, raising the differential of IgG4-related disease; however, the absence of storiform fibrosis and obliterative phlebitis, combined with the clinical and serologic profile, favored Kimura disease. This case is notable for its rare epitrochlear location, extensive neural involvement, concurrent diffuse cutaneous eruption, and histopathologic overlap with IgG4-related disease, highlighting the diagnostic challenges posed by atypical presentations of Kimura disease.

Abstract Background Dalbavancin is increasingly used off-label for chronic Gram-positive bone and joint infections (BJIs) requiring prolonged antimicrobial therapy, but optimal dosing strategies and the role of therapeutic drug monitoring (TDM) remain unclear. We evaluated the real-world implementation of a proactive TDM-guided dalbavancin workflow within an outpatient parenteral antimicrobial therapy (OPAT) programme. Methods Single-centre prospective observational implementation study including adult patients with BJIs consecutively treated with dalbavancin in OPAT service between July 2022 and August 2025. A multidisciplinary team developed a workflow incorporating TDM-guided pharmacokinetic modelling to individualize dosing intervals after fixed initial administrations (Days 1, 8 and 43). Target Cmin concentrations were ≥8 mg/L, later increased to ≥15 mg/L after European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint revision. Primary outcomes included implementation metrics (feasibility, fidelity and appropriateness). Secondary outcomes were clinical effectiveness, safety and overall workflow success. Results The workflow was applied to 101 patients accounting for 418 TDM-guided dalbavancin administrations (feasibility). Three patient-driven treatment discontinuations were observed (3/101, 3.0%), and scheduled administrations occurred within the predefined time window in 335/418 (83.5%) of cases (fidelity). Pharmacological target attainment was achieved in 285/342 (89.6%) of administrations without dosing delays (appropriateness). Clinical effectiveness was achieved in 55/73 (75.3%) patients completing therapy, with 28/101 (28%) still on treatment. Adverse events–related discontinuation occurred in 3/101 (3%) patients. Overall workflow success was observed in 74/101 (73.2%) patients. Conclusions A multidisciplinary TDM-guided dalbavancin workflow within an OPAT programme was feasible and safe, achieving high target attainment and favourable clinical outcomes. This approach supports individualized long-acting dalbavancin therapy for complex chronic BJIs.

Abstract Background Postoperative spinal implant infections (PSIIs) are a serious complication of instrumented spinal fusion. Although debridement with implant retention is standard for early infection, the optimal duration of antimicrobial therapy remains uncertain. Methods We conducted a multicenter retrospective cohort study across 10 US academic centers, including adults with early PSII (≤90 days after fusion surgery) from 2017 to 2021. We excluded patients who experienced treatment failure within 6 weeks of debridement. The primary outcome was treatment failure. Antibiotic therapy effect was analyzed as a time-varying exposure using adjusted Cox proportional hazards models. Secondary analyses included 12-week landmark and clone-censor-weighted models to compare durations ≤ 12 weeks versus >12 weeks. Results A total of 116 patients out of 499 (23.2%) experienced treatment failure during a median follow-up of 3.2 years. Among patients who remain failure-free 6 weeks from debridement, being on antibiotics was not associated with treatment failure (adjusted hazard ratio [aHR] 0.71; 95% CI .48–1.07; P = .10). In a 12-week landmark analysis limited to 359 patients who were not on indefinite suppressive antibiotic therapy, treatment durations > 12 weeks did not significantly reduce the risk of failure (aHR 1.01; 95% CI .62–1.64; P = .99). Results were consistent in the clone-censor-weight sensitivity analysis (aHR 0.85; 95% CI .62–1.16; P = .30). Conclusions Prolonged antibiotic therapy was not associated with improved outcomes in early PSII managed with debridement and implant retention. These results support shorter, individualized antibiotic courses in patients with adequate surgical source control.

Abstract Background The number of arthroplasty procedures and infection-related complications, including prosthetic joint infections (PJIs) and surgical site infections (SSIs), continues to rise. Although current guidelines recommend cefazolin or cefuroxime as the first-line perioperative prophylactic antibiotic, substitutions with non-cephalosporins remain common, especially among patients with reported β-lactam allergies. These substitutions may increase infection risk and healthcare costs. Evidence comparing outcomes across antibiotic classes remains variable. Methods We conducted a systematic review and meta-analysis of studies comparing single-agent cephalosporin versus single-agent non-cephalosporin prophylaxis in adults undergoing primary arthroplasty. Cochrane, Embase, Medline, Scopus, and Web of Science were searched from database inception through January 2025. Random-effect or fixed-effect models were used to estimate pooled odds ratios (OR) and 95% confidence intervals (CI). Subgroup analyses stratified results by cephalosporin type, study era, and risk of bias. Results Twenty-three studies (7 randomized controlled trials and 16 observational studies) were included, encompassing 191 527 arthroplasties in the cephalosporin arm and 20 058 in the non-cephalosporin arm. The odds of PJI were lower with cephalosporins (OR 0.59; 95% CI, .46–.75). No overall difference was observed for SSI (OR 0.70; 95% CI, .36–1.36), though post-2013 studies and the cefazolin subgroup demonstrated a significant protective effect. Randomized trial estimates were limited and heterogeneous and did not reach statistical significance. Certainty of evidence was graded as moderate. Conclusions Cephalosporins, particularly cefazolin or cefuroxime, remain the preferred prophylactic agents for primary arthroplasty. This quantitative synthesis reinforces their protective association against prosthetic joint infection and supports adherence to guideline-endorsed prophylaxis.

Abstract Objective: Suppressive antibiotic therapy (SAT) is used to prevent recurrent prosthetic joint infections (PJI) among patients who undergo debridement, antibiotics, and implant retention (DAIR). We aimed to assess SAT outcomes among younger, immunocompetent patients. Design: Retrospective cohort study. Patients: Immunocompetent patients <65 years of age who received DAIR for PJI of the hip, knee, or shoulder. Setting: Veterans Affairs hospitals. Methods: SAT was divided into short-term (oral antibiotics given for <3 months after guideline concordant therapy) and long-term SAT (>3 months to 5 years of oral antibiotics). The primary outcome was treatment failure (TF) and mortality combined. SAT was a time-dependent covariate in Cox proportional hazards models. Results: Of the 938 patients, 15% received short-term SAT, 20% received long-term SAT, and 65% did not receive SAT. Short- and long-term SAT were significantly associated with decreased hazards of TF or mortality (short-term SAT adjusted hazard ratio (aHR) = 0.27; 95% confidence interval (CI): 0.11, 0.67; Long-term SAT aHR = 0.52; 95% CI: 0.30, 0.89). Short-term SAT was significantly associated with C. difficile infection (aHR: 3.47; 95% CI: 1.38, 8.74). Short-term SAT (aHR: 7.83; 95% CI: 4.80, 12.77) and long-term SAT (aHR: 1.68; 95% CI: 1.19, 2.38) were significantly associated with antibiotic-associated diarrhea. Long-term SAT was not significantly associated with TF alone (aHR = 0.61; 95% CI: 0.32, 1.16). Conclusions: SAT was significantly associated with decreased death or TF and increased side effects. Benefits and risks must be weighed before prescribing SAT to younger, immunocompetent patients.

Abstract Background Native vertebral osteomyelitis (NVO) is a life-threatening spinal infection with rising incidence and significant morbidity. Despite its growing burden, long-term data on clinical characteristics, management trends, and outcomes remain limited. Methods We conducted a 26-year multicenter retrospective cohort study of adults (≥18 years) diagnosed with NVO at Mayo Clinic sites between 1999 and 2024. Demographic, microbiologic, treatment, and outcome data were analyzed across five time periods. Predictors of treatment failure were assessed using a multivariable competing risk model. Results Among 1255 patients (median age 67; 66% male), lumbosacral involvement was most common (65%), and 21% had multilevel involvement. Pathogens were identified in 77%, most commonly Staphylococcus aureus (49%; Methicillin-susceptible S. aureus 37%, methicillin-resistant S. aureus 13%). Over time from 1999–2004 to 2020–2024, Gram-negative bacilli increased from 6% to 14% (P = .048). Comorbidities including chronic kidney disease (10% to 21%), active chemotherapy (6% to 11%), and immunosuppression (8% to 17%) increased significantly. Additionally, 1-year treatment failure declined (16% to 10%). In multivariable analysis, diabetes mellitus (subdistribution hazard ratio [sHR] 1.92, 95% CI 1.18–3.13) and multilevel involvement (sHR 1.67, 95% CI 1.17–2.38) were associated with increased incidence of treatment failure, while concurrent infections (sHR 0.57, 95% CI 0.37–0.87) and higher Charlson Comorbidity Index (sHR 0.62, 95% CI 0.43–0.90) were associated with lower failure. Conclusions This large multicenter cohort highlights increasing host complexity, shifting microbiology, and predictors of failure, emphasizing the importance of early risk stratification and tailored strategies, such as multidisciplinary evaluation and close follow-up of high-risk patients to improve outcomes.

Abstract Background Catheter related bloodstream infections (CRBSI) are associated with increased resource use, treatment costs, and mortality among patients with cancer. Coagulase-negative staphylococci (CoNS) are the most common cause of central venous catheter (CVC) infection in this population. While CVC removal remains the gold standard, CRBSI with CoNS is sometimes managed with CVC salvage, despite incomplete safety and efficacy data in patients with hematological malignancy.Table 1.Baseline Demographic and Clinical DataTable 2.Baseline Characteristics by Treatment Strategy Methods A retrospective review was conducted of adult patients at Mayo Clinic Rochester from 2013 to 2024 diagnosed with hematological malignancy and CRBSI with CoNS. Patients were included in a “CVC removed” group if the line was removed within 5 days of bacteremia onset, and all others were included in a “CVC retained” group. Electronic medical records were evaluated for relevant clinical comorbidities, risk factors, and management. The primary outcomes of interest were 90-day mortality and relapse. To control for baseline differences between groups, we employed a propensity weighted analysis based on inverse probability of treatment weighting using the propensity score.Weighted cumulative event rates for Relapse and Mortality Results A total of 140 cases were included, of whom 95 (67.9%) had undergone BMT and 111 (80.4%) were neutropenic at time of CRBSI. The predominant CoNS identified was Staphylococcus epidermidis (88.6%). 79 (56.4%) patients had the CVC retained and 61 (43.6%) underwent CVC removal. Those in whom the CVC was retained were more likely to be BMT recipients (p=0.007). However, line removal was more common with PICC lines (p&lt; 0.001) and in those hospitalized for management of line-associated bacteremia (p=0.022). Within 90 days, there were 10 patients (cumulative incidence 8.2%) who had microbiological relapse (2 [4.3%] in the CVC removed group and 8 [11.1%] in the CVC retained group). Propensity weighted analysis demonstrated significantly higher rate of microbiologic relapse with CVC retention (p=0.043) but no difference in mortality (p=0.128), as shown by weighted cumulative event rate curves in Figure 1. Conclusion Despite the finding of increased risk of relapse associated with CVC retention, there was no significant difference in mortality between CVC removal and retention among individuals with CoNS CRBSI and hematological malignancy. Disclosures All Authors: No reported disclosures

Abstract Background The increased frequency of spinal surgeries has led to a rise in postoperative spine infections (PSIs), now recognized as the third most common surgical complication. Currently, there is no standardized definition of PSI, complicating clinical management and research. This meta-epidemiological study aimed to develop clear diagnostic criteria to assist clinicians and researchers in identifying and reporting PSIs consistently. 2020 PRISMA flow diagram Sankey diagram showing the distribution of combination of criteria or definitions used by the authors. This refers to 21 articles that used a definition derived by the authors. Methods Following PRISMA guidelines, a comprehensive literature search was conducted by a medical librarian using Ovid MEDLINE (March 14, 2024). Studies were included if they reported on at least ten adult patients diagnosed with PSI and provided clear diagnostic definitions. The primary objective was to evaluate existing PSI diagnostic criteria and categorize them into thematic clusters. We constructed standardized diagnostic combinations using 13 predefined criteria derived from clinical practice guidelines and prior research (Table 1).Characteristics of the included studies*Total can be more than 100% since some variables can be present in multiple categories.This refers to 21 articles that used a definition derived by the authors. For articles #411 and #630 categorization was not possible as the definition provided only information about the depth of infection and not the criteria for diagnosis. Article #1148 was included as, defining “presumed aspetic” cases meant, by definition, also defining infectious cases.Abbreviations. The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP), Centers for Disease Control and Prevention (CDC), The National Healthcare Safety Network (NHSN), Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA), Magnetic Resonance Imaging (MRI) Results From an initial 1,466 studies screened, 101 were included (Figure 1). Most studies were retrospective (91/101, 92.1%), and a majority (77/101, 76.2%) relied on established criteria such as those from the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) or the CDC. Seven studies combined predefined criteria with additional detailed explanations. Among the remaining studies using independent definitions, clinical signs and symptoms were the most common criteria (13/24, 54.2%) (Table 1). Criteria were grouped into clinical, microbiological, and radiological categories, with most studies primarily using clinical criteria alone or in combination with microbiological or imaging findings (Figure 2). Conclusion There was no clear consensus in the literature on what defines a PSI. Our findings emphasize the necessity of establishing a standardized PSI definition that integrates clinical, microbiological, and radiological criteria. Implementing such a unified framework could enhance diagnostic accuracy, address existing limitations associated with hardware complications, wound drainage interpretations, and imaging ambiguities, and improve upon the current shortcomings of surveillance systems. Disclosures Jeremy D. Shaw, MD, Globus: Grant/Research Support|Purgo Scientific: Advisor/Consultant|Purgo Scientific: Stocks/Bonds (Private Company)

Abstract Background Spinal implant infections (SII) are serious complications following instrumented spinal fusion. Debridement with implant retention requires antibiotic therapy, yet the optimal duration remains unclear. We assessed whether longer antibiotic duration is associated with reduced risk of treatment failure. Methods We conducted a multicenter retrospective cohort study of adult patients diagnosed with acute postoperative SII (≤90 days from index surgery) between January 1, 2017, and December 31, 2022. All patients underwent debridement with implant retention. Treatment failure was defined as unplanned reoperation, clinical recurrence, or infection-related death. A Cox proportional hazards model assessed whether being on antibiotics was protective, treating antibiotic use as a time-dependent covariate, adjusting for relevant clinical variables, and including death not attributable to infection as a competing event. A second Cox model evaluated whether shorter antibiotic duration was associated with increased risk of failure with landmark analysis at six weeks. Results There were 531 patients included in the study. Patient demographics are described in Table 1. During a median follow-up of 1,168 days (IQR 576-1,817), 151 patients experienced treatment failure. There was a non-significant trend toward decreased hazard of failure while on antibiotics (HR 0.70; 95% CI 0.46–1.05; p=0.087). Among 363 patients without early failure, 60 (16.5%) received ≤6 weeks of antibiotics and 303 (83.5%) received &gt;6 weeks. Longer antibiotic duration was not associated with a differential risk of failure (HR 0.75, 95% CI 0.43–1.33; p=0.34). Conclusion Continuing antibiotic therapy after debridement and implant retention may help reduce the risk of treatment failure in SII. However, it remains unclear whether extending antibiotic treatment beyond a certain duration continues to offer additional benefits. Prospective studies are needed to better define the optimal duration and approach to antibiotic therapy in these scenarios. Disclosures Sandra B. Nelson, MD, UpToDate Wolters Kluwer Health: Author, Editor