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Abstract Background Good syndrome (GS) is an under-recognized adult-onset immunodeficiency characterized by the coexistence of thymoma and hypogammaglobulinemia. It is marked by recurrent infections, combined B- and T-cell immunodeficiency, and frequent autoimmune manifestations. Its rarity, unclear pathogenesis, and often delayed diagnosis contribute to its clinical complexity.Distribution of Infections by pathogen type in patients with Good Syndrome: the microbiological spectrumDemographics, clinical characteristics, thymoma classification with staging and management Methods We conducted a retrospective review of adults diagnosed with good syndrome at Mayo Clinic up until 2024. We assessed baseline characteristics, clinical features with a particular focus on infectious complications, immunological lab parameters, thymoma histopathology with staging, and management. Descriptive statistics were utilized for analysis.Immunological lab parameters and management of Good syndrome Results During the study period, Good syndrome was diagnosed in 32 patients; 78% were male, with a median age at diagnosis of 62 years (Table 1). All patients had thymoma, the majority of which were stage I (localized), and most underwent thymectomy as part of management. The median delay in GS diagnosis following thymoma diagnosis was 1,486 days (interquartile range IQR: 406.75–1,992.75). Infectious complications were observed in 30 of 32 patients (97%), most commonly sinopulmonary infections (87%) (Figure 1). Bacterial infections were documented in 29 patients (94%), viral in 14 (45%), fungal in 13 (42%), and mycobacterial in 3 (10%) (Figure 2). Immunologic data were available for 22 patients. Reduced CD4+ T-cell counts and severe B-cell lymphopenia were observed in 77%. IgM and IgG deficiencies were the most prevalent, present in 82% of cases. Most patients received monthly immunoglobulin replacement; additionally, 59% were prescribed oral antimicrobial prophylaxis due to their elevated risk of infections. All-cause mortality was 31% (n=10); among these, 3 deaths (10%) were directly attributable to complications of Good syndrome. Conclusion We observed a significant delay (Median of 4.07 years) in the diagnosis of Good syndrome following thymoma detection. Given the high risk of infectious complications and associated mortality, clinicians should maintain a high index of suspicion and consider early immunologic evaluation in adults with recurrent or opportunistic infections, particularly in the context of a known thymoma. Disclosures All Authors: No reported disclosures

Abstract Background Revaccination is required for patients who receive a hematopoietic cell transplant (HCT) to reduce vaccine preventable illness. Revaccination requires an individualized plan due to differences in immunosuppressive therapy, immune reconstitution, age, and other challenges such as graft versus host disease. A structured approach is required to ensure prompt initiation of re-vaccinations and completion of the re-vaccination schedule. This study sought to evaluate the re-vaccination process at our center as a baseline for quality improvement. Methods We conducted a retrospective chart review of pediatric patients who received an autologous or allogeneic HCT between January 2019 and March 2024 to assess time to starting re-vaccination after post-HCT medical clearance and percentage of patients up to date within each series of vaccinations per internal protocol. Results A total of 64 patients were evaluated, of whom 23 were female and 35 underwent allogeneic stem cell transplant. For analysis, 13 were excluded due to death prior to clearance for vaccination. Among those included, 42 patients were cleared for restarting vaccines, and 37 (88%) of those have received at least one vaccine, while only 25 (59%) have completed the first series of recommended vaccines. The average time from transplant to administration of the first vaccine was 431 days for autologous HCT and 459 days for allogeneic HCT. The average time from medical clearance to the first vaccine was 66 days. The mean interval between the first and second vaccine doses was 97 days. Conclusion The majority of eligible patients initiated re-vaccination after transplant, but rates for the receipt of full recommended initial series remained suboptimal, with notable delays with notable delays between transplant and the day of clearance as well as clearance and the first vaccine administered. These findings highlight significant gaps in post-transplant immunization practices and underscore the need for targeted interventions to optimize protection for this vulnerable population. Disclosures All Authors: No reported disclosures

Abstract Background Phage therapy has emerged as a generally safe approach, as demonstrated in preclinical and clinical studies. However, data on efficacy, including optimal dosing frequency, remain limited. MRSE is a leading cause of foreign body-associated osteomyelitis and a potential target for phage therapy. Here, the activity of phage K alone and in combination with vancomycin (VAN), administered once (QD) or three times (TID) daily, against biofilms formed by two orthopedic infection-associated MRSE isolates on orthopedic screws was evaluated.Fig 1.in vitro multi-dose assay of methicillin-resistant S. epidermidis biofilm-coated cortical bone screws.IDRL, Infectious Diseases Research Laboratory; DMEM, Dulbecco's Modified Eagle Medium; PBS, phosphate-buffered saline; CFU, colony-forming units. Created in https://BioRender.comFig 2.Quantities of biofilm on screws after 24 hours of treatment.*Log10 CFU/cm² of biofilm on screws before treatments. Biofilm burden of the MRSE isolates prior to treatment ranged from 5.7 to 6.3 log10 CFU/cm². A Kruskal-Wallis test was performed to evaluate the statistical significance of biofilm reduction between treatment groups. The minimum inhibitory concentration (MIC), minimum biofilm inhibitory concentration (MBIC), and minimum biofilm bactericidal concentration (MBBC) of vancomycin for both IDRL-9410 and IDRL-9403 were 2, 2, and >128 µg/mL, respectively. Methods MRSE IDRL-9410 and IDRL-9403 biofilms were formed on titanium cortical bone screws (D 1.5 mm, L 4 mm, surface area 0.33 cm²) in 0.2 mL of tryptic soy broth containing 10⁶ CFU/mL (Fig 1); testing was performed in triplicate on two separate days. After 24 hours, screws were rinsed with PBS and randomly assigned to: Dulbecco’s Modified Eagle Medium (DMEM); vancomycin (VAN, 20 μg/mL) in DMEM; phage K (10⁹ PFU/mL) in DMEM; or VAN and phage K in DMEM. Every 8 hours, screws from the TID groups were transferred to new plates containing fresh treatment, with QD groups left in the original material. 24 hours post-treatment, screws were quantitatively cultured. Bactericidal activity was defined as ≥ 3 log₁₀ CFU/cm² reduction compared to the DMEM group, and synergy as ≥ 2 log₁₀ CFU/cm² reduction in the combination group compared to VAN or phage alone. Results After 24 hours, bactericidal activity was observed for QD and TID VAN-phage K groups against IDRL-9410 (p < 0.05 and p < 0.01, respectively) and IDRL-9403 (both p < 0.01). Synergy was observed in the VAN-phage K QD group, with a 2.2 log₁₀ CFU/cm² reduction for IDRL-9410 compared to VAN alone (Fig 2). 3.0 and 5.3 log₁₀ CFU/cm² reductions were observed in the VAN TID groups for IDRL-9410 and IDRL-9403, respectively, compared to the DMEM group (both p < 0.01). There was no statistically significant difference in biofilm reduction between the QD and TID groups for phage K alone or VAN-phage K for either strain. Conclusion Combination treatment with phage K and VAN, administered QD or TID, showed greater biofilm reduction compared to phage K alone. Increasing phage dosing frequency did not enhance biofilm reduction under the conditions studied. Disclosures Robin Patel, MD, a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication, a patent on PET imaging of bacterial infection: a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication, a patent on PET imaging of bacterial infection|MicuRx Pharmaceuticals and bioMérieux: Grant/Research Support|PhAST, Day Zero Diagnostics, DEEPULL DIAGNOSTICS, S.L., Nostics, HealthTrackRx, bioMérieux and CARB-X: Advisor/Consultant|Up-to-Date and the Infectious Diseases Board Review Course: Honoraria

Abstract Background Stigma associated with tuberculosis (TB) and TB diagnosis is a major social factor in delay of diagnosis and non-adherence to TB treatment among Asian American and Pacific Islander (AAPI) populations. Main sources of stigma include misconceptions regarding TB transmission and lack of knowledge about symptoms or treatment.Figure 1.Respondent demographicsBreakdown of respondent demographics by age, gender, and AAPI subgroup.Figure 2.Demographic breakdown of TB awarenessTB awareness by AAPI subgroup, age, and gender. Methods A cross-sectional survey of 666 AAPI individuals analyzed TB symptom recognition, transmission misconceptions, and awareness in two AAPI community centers. Data were segmented by AAPI subgroup, metropolitan area (Seattle/Tacoma vs. Las Vegas), age, and gender.Figure 3.TB transmission beliefs.Figure 4.TB treatment, curability, and latent TB infection awareness. Results Overall, 76.6% of respondents reported TB awareness, varying by AAPI subgroup. Awareness was highest among Korean (95%) and Filipino (91%) participants, and lowest among Vietnamese (52%) and Cambodian (50%) respondents. Regionally, TB awareness was similar between Tacoma (76%) and Las Vegas (79%). Age and gender significantly impacted awareness. Respondents under 18 had the lowest TB awareness (59%), while those aged 18-34 had the highest (84%). Females reported higher TB awareness (79%) and symptom recognition (61%) than males (74% and 46%, respectively). Symptom knowledge varied. 55% were aware of TB symptoms, but only 16% were able to recognize five common TB symptoms. Misconceptions about transmission also persisted broadly. Out of the 71% of respondents who were aware that TB is transmissible, many incorrectly believed TB spread via shaking hands (35%), sharing food/drinks (50%), or touching items in public areas (37%). The 45-64 and 65+ age groups were most prone to misconceptions about transmission. While 72% of respondents were aware that TB could be treated, only 57% knew TB could be cured. 30% of respondents were aware of latent TB infection. Conclusion Significant disparities in TB awareness exist in AAPI communities. Females demonstrated greater TB awareness perhaps due to cultural differences (“caretaker role”), while TB transmission misconceptions were prevalent among older individuals. Limited knowledge on LTBI and TB treatment represent significant barriers to effective TB control. Tailored educational efforts will be required to improve TB awareness and reduce misconceptions within AAPI communities. Disclosures All Authors: No reported disclosures

Abstract Background According to consensus guidelines, area under the concentration–time curve (AUC) is recommended for vancomycin dosing rather than trough-based monitoring, but transition to AUC-based dosing requires substantial staff education and resource allocation. We sought to evaluate the level of congruency between vancomycin total daily doses (TDD) determined using a trough concentration goal of 10-15 mcg/mL compared with an online Bayesian calculator targeting an AUC of 400-600 mg·h/L.Patient DemographicsInitial Dose Results Methods We performed a retrospective, multicenter cohort study of vancomycin therapeutic drug monitoring (TDM) in non–critically ill adults hospitalized from March 1, 2017-December 31, 2021. Patients were included if they received intravenous vancomycin for ≥72 hours with a documented trough target of 10 to 15 mg/L, had ≥1 serum vancomycin trough concentration assessed at steady state, and received ≥2 doses of vancomycin after serum assessment with or without dose adjustment. Using an online vancomycin calculator with Bayesian modeling, the study team input patients’ trough-based dosing data to retrospectively estimate the initial vancomycin AUC exposure achieved and the initial and post-trough TDD recommended for an AUC target of 400 to 600 mg⸱h/L. The initial and post-trough vancomycin total daily dose (TDD) derived by the online calculator were compared with the actual doses used for each patient when a trough concentration of 10 to 15 mg/L was targeted.Comparison of Trough-Based and AUC-Based Dosing of Vancomycin AUC indicates area under the concentration–time curve; TDD, total daily dose. Dashed line indicates where the 2 methods are equal; shading indicates where the 2 methods are within 20% of each other Results In total, 89 patients were included in the study. The actual vancomycin TDD with trough monitoring (target, 10-15 mg/L) was within 20% of the recommended AUC-based TDD for 62 patients (70%) with initial dosing and for 74 (83%) after the initial trough concentration. Nephrotoxicity was rarely observed (2%) and the median duration of vancomycin was 4 days. Conclusion Given the frequency of dosing similarity between 400-600 mg·h/L AUC and 10-15 mg/L trough-based dosing, vancomycin trough-based monitoring to a goal of 10-15 mg/L is an option warranting further exploration. Disclosures All Authors: No reported disclosures

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< 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 Staphylococcus aureus is a challenging pathogen which causes a multiplicity of human diseases around the globe, acquired in the community and healthcare settings alike. Treatment of S. aureus infection can be challenging and is further compromised by antimicrobial resistance. Understanding of its pathogenesis, transmission pathways and the dynamics of its genome evolution and associated adaptations is incomplete. One strategy to assess genome evolution is to assess codon bias. Historically, studies have focused on the consequences of coding changes; assessing silent mutations in the form of synonymous codon usage bias represents a novel approach to studying genetic adaptation.Figure 1.Principal component analysis (PCA) (A) and sPLS-DA (B) separate S. aureus from complex mates.sPLS-DA component 1 relies on a hypothetical protein, identified here by its NCTC 8325 genomic coordinates, as important for separating S. aureus from complex mates (C). Methods Here, the codon bias of 2,872 genes was queried against all publicly available complete S. aureus plasmids and genomes. Using public BioSample data, genomes were sorted by disease state (e.g., bacteremia, pulmonary infection) and geographical collection site. Results Isolates from Nairobi, Kenya were most different from other isolates, suggesting that geographical isolation may shape codon bias signature. In addition, codon bias of two MSCRAMM proteins implicated in human disease - SdrC and FnBPB - varied between isolation sources, suggesting a role for codon bias in S. aureus genetic adaptation to selective pressures of infection. Additionally, codon bias out-performed coding and nucleic acid mutational metrics in separating members of the S. aureus complex, S. aureus, Staphylococcus argenteus, Staphylococcus schweitzeri, and Staphylococcus roterodami; Fig 1, sparse partial least squares analysis (sPLS-DA) mean AUC codon: 0.89762, nucleic acid: 0.82266, codon bias: 0.9996 (relying on hypothetical protein NC_007795.1:516850-517419). Conclusion This analysis suggests that codon bias in S. aureus is a source of genetic adaptation that can be used to separate strains by geographical isolation source, and separate S. aureus sensu stricto from other S. aureus complex members. Disclosures Nicholas Bedard, MD, Stryker: Advisor/Consultant Robin Patel, MD, a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication, a patent on PET imaging of bacterial infection: a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication, a patent on PET imaging of bacterial infection|MicuRx Pharmaceuticals and bioMérieux: Grant/Research Support|PhAST, Day Zero Diagnostics, DEEPULL DIAGNOSTICS, S.L., Nostics, HealthTrackRx, bioMérieux and CARB-X: Advisor/Consultant|Up-to-Date and the Infectious Diseases Board Review Course: Honoraria

Abstract Background In 2019, the US performed 290,000 breast reconstructions with an estimated infection rate of 3-35%. Tissue expander infections detract from desired aesthetic effects, delay adjuvant treatments, increase morbidity and mortality, and have high recurrence rates (20-40%). Little is known about risk factors for recurrent tissue expander infections, particularly the impacts of different treatment modalities. Methods We conducted a single-center retrospective cohort study of adult women post-mastectomy who developed microbiologically-proven tissue expander infection between the period of 2017 – 2024. Outcomes including 12-month infection recurrence and risk factors for recurrence were compared between surgical versus nonoperative groups, as well as between three surgical strategies (i.e., one-stage, two-stage, explantation). Unadjusted and adjusted logistic regression models were used to assess the associations between the treatment modalities and the outcomes. Univariate models assessed the relationship between the covariates of interest and infection recurrence. Results 107 patients were included, with the majority treated with combination of antibiotics and surgical therapy (Table 1). There was no significant difference in outcomes when the operative versus antibiotics alone cohorts were compared (Table 2). The odds of infection recurrence and rehospitalization in patients who underwent two-staged exchange or explantation were significantly lower when compared with the one-staged group (Table 3). Univariate modeling found severity and radiation therapy to be numerically more common in the group experiencing recurrence, with a trend towards statistical significance (Table 4). Conclusion Our study demonstrates reduced risk of recurrent tissue expander infection with two-staged exchange or explantation, compared to one-staged exchange. Though limited by small sample size, the strengths of our study include our presentation of the real-world variability of these syndromes and their management, adjustment for infection severity and other potential confounders; and the focus on microbiologically-defined infections. Disclosures All Authors: No reported disclosures

Abstract Background The COVID-19 pandemic saw a worrisome rise in mucormycosis cases in India, especially among those receiving corticosteroid therapy. While corticosteroids are essential for managing severe COVID-19 cases, their immunosuppressive action appears to augment infection risk. Clinically, prolonged steroid use may result in severe forms of mucormycosis; however, this requires rigorous systematic evaluation. Methods We conducted an exhaustive analysis of 327 mucormycosis cases and 596 COVID-19 controls, all of whom were treated during the second wave in India. Exposure to steroids was carefully categorized by duration into three groups: short-term (1-5 days), standard-term (5-10 days), and long-term ( > 10 days). Each case was biopsy-proven, with further radiographic confirmation of disease extent. Special emphasis was laid on intracranial extension as a marker of severity, along with tracking treatment outcomes and survival. Statistical modeling was used to correct for important confounders, including diabetes status, glycemic control, and concurrent use of other immunomodulators. Results The results were striking. Those receiving steroid treatment for more than ten days of duration had a nearly fourfold higher incidence of intracranial mucormycosis compared with short-term-treated patients (38.2% vs. 12.5%, p< 0.001). Each day of steroid use accounted for a 12% increase in associated risk. While mortality rates were equal, patients receiving prolonged treatment had a considerably increased number of surgical procedures (35.3% vs. 16.7%, p=0.02) as well as more complicated hospitalization. Those with diabetes were especially sensitive to such effects of prolonged treatment. Conclusion The study highlights the role of cautious use of corticosteroids in the management of COVID-19. Our work gives strong evidence for the importance of compliance with guideline-based recommendations for corticosteroid duration, especially for high-risk populations. This study empowers healthcare practitioners with unequivocal evidence to provide optimal COVID-19 treatments while avoiding the risk of severe fungal infection. Disclosures All Authors: No reported disclosures

Abstract Background Posaconazole immediate release (IR) suspension is the standard product for enteral feeding tube (EFT) administration but has erratic pharmacokinetic behavior and results in sub satisfactory concentrations. Limited evidence suggests that the posaconazole oral delayed-release (DR) tablets may be crushed. Methods This was a retrospective cohort study of hospitalized adults who received EFT administration of posaconazole IR suspension or crushed DR tablets between 2018 and 2024. Patients were eligible if they had at least one serum concentration drawn ≥5 days after posaconazole initiation. The primary outcome was the attainment of therapeutic (≥700ng/mL for prophylaxis, ≥1,000ng/mL for treatment) serum concentration within 30 days. Secondary outcomes included time to therapeutic serum concentration, adverse drug effects, and frequency of clogged EFT. Multivariable cox proportional hazards regression was used to assess the relationship between posaconazole formulation and attainment of therapeutic concentrations while adjusting for confounding variables. Results Of the included patients, 100 received DR tablets and 48 received IR suspension. There were no significant differences in baseline characteristics or severity of illness. Among DR tablet and IR suspension recipients, 59% and 23% achieved therapeutic concentrations, respectively (p < 0.001). After adjusting for age, sex, BMI, drug interactions, posaconazole indication, malabsorptive gastrointestinal conditions, IR suspension was significantly less likely than crushed DR tablets to achieve therapeutic posaconazole concentrations within 30-days (HR 0.37, 95% CI 0.20-0.71; p < 0.003). The crushed DR tablet group required less total daily posaconazole to achieve therapeutic concentrations (400 vs 600 mg/day, p = 0.003). Clogged EFTs were more frequent in the crushed DR tablet group (27% vs 10%, p = 0.022), while no differences were observed in the occurrence of hepatotoxicity or hypokalemia. Conclusion Administration of crushed posaconazole DR tablets via EFT is more likely to attain therapeutic concentrations compared to IR suspension. The optimal technique for administering crushed DR tablets to prevent EFT complications warrants investigation. Disclosures Patrick M. Wieruszewski, PharmD, FCCM, Wolters Kluwer/UpToDate: Advisor/Consultant