Kerkelis, Melissa

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 Beta-lactam pharmacokinetics can be significantly altered in patients with malignancy. Therapeutic drug monitoring (TDM; i.e., drug level testing) may facilitate pharmacokinetic/pharmacodynamic (PK/PD) target attainment, but the data are limited. This study aimed to characterize PK/PD target attainment of anti-pseudomonal beta-lactams in hematology/oncology patients.Table 1:Case DescriptionGraph 1:Distribution of Beta-Lactam TDM Indications Methods We conducted a retrospective review of beta-lactam TDM performed between June 2022 and June 2024 in hospitalized adults with hematologic or solid organ malignancies. We included patients who underwent beta-lactam TDM during clinical care, typically for extracorporeal membrane oxygenation (ECMO), extremes of body weight, suspected augmented renal clearance, multidrug-resistant infection, or suspected dose-dependent beta-lactam toxicity. Primary outcomes were (1) the proportion achieving target beta-lactam concentrations and (2) the proportion undergoing antibiotic dose adjustment based on TDM results.Table 2:Institutional Dosing Guidelines Results There were 47 TDM episodes in 20 unique patients. Considering only the first TDM per patient, 10 (50%) patients achieved target concentrations, 2 (10%) were below target, and 6 (30%) were above target. Antibiotic dose adjustments were made in 8 (40%) patients in response to TDM results. The most common indication for beta-lactam TDM was concerns regarding accurate renal clearance, followed by extremes of weight. Conclusion Retrospective findings suggest that beta-lactam TDM facilitated individualization of therapy in 40% of patients with either hematological or solid organ malignancy, with dose adjustments often intended to improve antibiotic safety. Future studies should refine the criteria for beta-lactam TDM use in this population and determine the need for tailored PK/PD targets in patients with impaired host response to infection. Disclosures All Authors: No reported disclosures

Abstract Background Hematopoietic stem cell transplant (HSCT) recipients are susceptible to infections with respiratory viruses resulting in higher morbidity and mortality. Parainfluenza virus (PIV) infection in the setting of leukopenia is associated with higher risk of lower respiratory tract infection and mortality. Intravenous immunoglobulin (IVIG) has been used as adjunctive treatment in viral respiratory infections, although data guiding its use is limited.Table 1:Patient CharacteristicsTable 2:Clinical Outcomes Methods We conducted a retrospective cohort study of adult HSCT recipients diagnosed with PIV infection at our institution from January 2014 to September 2024. Diagnosis of PIV infection was made via BioFire® Respiratory Panel multiplex polymerase chain reaction (PCR) or viral culture from nasopharyngeal or bronchoalveolar lavage. Data on clinical characteristics and outcomes were collected and reviewed.Table 3:Clinical Outcomes for Patients with IgG <767 mg/dL Results A total of 110 HSCT recipients were diagnosed with PIV infection by PCR or viral culture within the study period. Patient characteristics and clinical outcomes are summarized in Tables 1 and 2. PIV type 3 was the most common, followed by PIV type 4 and type 1. Eighteen patients (16.36%) had co-infections with another virus. A total of 16 patients received IVIG at time of PIV infection. The mean cumulative IVIG dose was 28.75 grams. Patients who received IVIG were more likely to have been hospitalized due to symptoms related to the viral infection (p=0.03) and had a lower immunoglobulin G level (p< 0.001). Overall, there was no significant difference in rates of mechanical ventilation (12.5% vs 7.45%, p=0.616), development of secondary fungal or bacterial infection (12.5% vs 12.7%, p=1), or 90-day mortality (18.75% vs 6.38%, p=0.123) among patients treated with or without IVIG, respectively. Similarly, in a subset analysis of patients with IgG level < 767 mg/dL, there were no significant difference in outcomes for patients treated with or without IVIG (Table 3). Conclusion There were no significant differences in clinical outcomes, including rates of mechanical ventilation, secondary infections, or 90-day mortality, between HSCT patients who received IVIG and those who did not for PIV infection. Larger studies are needed to gain insight into efficacy of IVIG as adjunctive treatment in PIV infections in this population. Disclosures All Authors: No reported disclosures

Abstract Background Vascular graft infection (VGI) is a rare but serious condition. Pathogen identification can be difficult given the deep-seated nature. Microbial cell-free DNA next-generation sequencing (mcfDNA NGS) is an emerging tool in non-invasive microbiologic workup. One commercially available mcfDNA is the Karius Test (KT). There is a paucity of data regarding utility and impact of mcfDNA NGS testing in the evaluation of VGI. Methods We retrospectively evaluated adult patients who underwent KT for evaluation of VGI at our institution. Only patients who met the Management of Aortic Graft Infection Collaboration (MAGIC) classification for suspected or confirmed VGI were included. We investigated the concordance between KT and conventional microbiologic workup. Conventional workup (CW) included pathogen identification through blood cultures, peri-graft/graft cultures, or histopathology. Concordance was defined by identical pathogen identification on KT and CW. We examined the influence of the KT result on clinical management.Figure 1.KT Results for Confirmed and Suspected VGI. Results We identified 25 patients who met criteria for either suspected or confirmed VGI per the MAGIC criteria. Microbiology was undefined in 8 patients who had negative KT and negative CW. A total of 17 patients had positive workup with 6 having positive KT and negative CW, 3 having negative KT and positive CW, and 8 having both positive KT and positive CW (Table 1). KT was less likely to be positive for patients who met criteria for suspected infection (4/10; 40%) as opposed to confirmed infection (10/15; 66.67%), albeit non-significant (OR 0.33, p=0.188) (Figure 1). The KT led to antimicrobial de-escalation in 27.3% of patients with positive CW and 35.7% of patients with negative CW (Figure 2). Full concordance of KT and CW was noted in 3 patients (Table 2).Figure 2.Influence of KT on VGI cases with positive and negative conventional work-up. Treatment escalation was defined as the broadening of antimicrobial coverage due to KT results. Treatment de-escalation was defined as narrowing/discontinuation of antimicrobial coverage due to KT results. Conclusion We found that the positivity rate for KT was 56%. KT impacted management in 40% of cases. Patients with confirmed VGI had a higher likelihood of having a positive KT. KT was the only positive microbiological definitive test in one case. Further studies are needed to explore the utility and impact of KT in the workup of VGI. Disclosures All Authors: No reported disclosures

Abstract Background The underlying cause of fever of unknown origin (FUO) remains unidentified in up to 51% of cases despite systematic evaluation. Microbial cell-free DNA next-generation sequencing (mcfDNA-NGS) offers an agnostic, noninvasive approach to pathogen identification, but the utility and clinical impact of this assay in FUO remain unknown. Methods This retrospective cohort study evaluated adult patients referred for FUO evaluation at a tertiary medical center between November 2019 and November 2023. Patients underwent both standard microbiologic testing (ST) and mcfDNA-NGS. Diagnostic impact was assessed in 4 domains: new diagnoses, earlier time to diagnosis, avoidance of invasive procedures, and non-hypothesis-driven diagnoses. Logistic regression was used to identify predictors of positive mcfDNA-NGS testing. Results Among 176 patients, mcfDNA-NGS was positive in 44.3%, with 49% of these cases considered clinically significant. Infectious cause of FUO was identified in 39% of patients, noninfectious in 35%, and unknown in 26%. mcfDNA-NGS contributed to a positive diagnostic impact in 30% of cases, mainly by earlier diagnosis (16%) and potential for avoidance of invasive procedures (10%). Positive mcfDNA-NGS was significantly associated with higher Charlson comorbidity index score (odds ratio [OR], 1.22; P < .001) and white blood cell (WBC) count ≤4.5 × 109 cells/L (OR, 8.61; P < .001). Conversely, FUO without localization was associated with a decreased likelihood of positive mcfNDA testing (OR, 0.18; P < .001). Conclusions mcfDNA-NGS effectively complements ST in diagnosing FUO, providing earlier detection and minimizing invasive testing. Clinical predictors such as high comorbidity and low WBC count may guide the optimal use of mcfDNA-NGS in FUO. Prospective evaluation of optimal timing and use of mcfDNA-NGS and cost-benefit analysis in FUO is needed.