Transplant Recipients Research Articles

592. Immunogenicity and Safety of High-dose versus Double-dose Quadrivalent Inactivated Influenza Vaccine in Adult Kidney Transplant Recipients: A Randomized Controlled Trial

Abstract Background Both high-dose and double-dose inactivated influenza vaccines have been shown to better elicit a greater immune response compared to standard-dose influenza vaccine in solid organ transplant (SOT) recipients. However, a direct comparison between high-dose (HD) and double-dose (DD) quadrivalent inactivated influenza vaccine (QIIV) has not been explored. Methods From June to December 2023, we conducted an open-label randomized controlled trial to compare the immunogenicity and safety of the 2023 southern hemisphere HD QIIV at 60 ug (Effluelda, Sanofi) versus double standard-dose QIIV at 30 ug (Fluarix tetra, Sanofi) in adult kidney transplant (KT) recipients. Pre-immunization and 4-week post-immunization sera underwent strain-specific hemagglutination inhibition assays, and safety profiles were assessed. Results Eighty-four eligible KT recipients were randomly assigned to receive either HD QIIV or DD QIIV (42 each). Among them, 50 (59.5%) were male, with a mean age (SD) of 46 (11) years old, and 50 (60.7%) participants received kidneys from deceased donors. Common immunosuppressive regimens included mycophenolate mofetil (65.5%), tacrolimus (77.1%), and prednisolone (100%). SC to at least 1 strain was significantly greater in the HD QIIV group (95.2%) compared to the DD QIIV group (69%) (P = 0.006). The SC rate for A/H1N1, A/H3N2, B/Victoria, and B/Yamagata strains was higher in the HD QIIV group compared to the DD QIIV group, with the following percentages: 69.1% vs 52.4%, 52.4% vs 38.1%, 52.4% vs 42.9%, and 61.9% vs 40.5% (P = 0.118, P = 0.188, P = 0.382, and P = 0.049, respectively). In multivariate analysis, SC to at least 1 vaccine strain was significantly associated with the use of HD vaccine (OR 17.59, 95% CI [2.10, 147.22], P=0.008) and receiving the vaccine after 1-year post-KT (OR 34.76; 95% CI [2.59–454.45], P=0.007). There were significantly fewer occurrences of pain at the injection site and muscle ache in the HD QIIV group compared to the DD QIIV group, with the following percentages: 4.8% vs 19.0%, and 0% vs 9.5% (P = 0.040 and P = 0.043, respectively). Conclusion HD QIIV could marginally elicit a more pronounced immune response, alongside a comparatively reduced occurrence of adverse reactions, in adult SOT recipients when compared with DD QIIV. TCTR20230510005. Disclosures All Authors: No reported disclosures

P-2278. CMV Viremia and Disease in Pediatric Liver Transplant Patients: a Multi-national Systematic Review and Meta-analysis

Abstract Background Cytomegalovirus (CMV) viremia (Defined as a single detectable CMV RNA PCR) and disease (defined as CMV viremia with compatible systemic and/or localized signs and symptoms) remain a leading cause for mortality and morbidity in the pediatric solid organ transplant recipient. This systemic review aims at pooling data from the leading pediatric transplant institutions globally to identify the overall incidence of and risk factors associated with CMV viremia and/or disease in pediatric liver transplant recipients. PRISMA flow diagram Methods A systemic review of Pubmed and OVID databases was conducted since the inception to 01 April 2024. 24 articles were included from the USA, UK, South Africa, India, Japan, Finland, Canada, Turkey, Mexico, Thailand, Greece, Israel and Australia. A total of 1964 liver transplants were included. Median age was 50 months with 47.8% males. Data related to demographics, incidence, donor and recipient CMV serological classification (Donor (D) and Recipient (R)) and risk factors for CMV viremia/disease were extracted from the articles and subsequently analysed. This review was registered in Prospero: CRD42023477476 Results The Incidence of CMV viremia and disease in pediatric liver transplant patients in this review were 34% and 8.4% respectively, with statistically significant higher risk in the CMV D+/R+ category compared to other D/R serologic groups (P value < 0.05). , Additional risk factors identified for CMV viremia/disease included younger age, biliary atresia, high steroid doses, and rejection attacks. Conclusion This meta-analysis highlights that CMV viremia and disease post-liver transplantation are significant health concerns in pediatric populations. Identifying high risk populations for targeted CMV monitoring and potentially preemptive therapy to mitigate CMV-associated morbidity and mortality is a critical cornerstone of pediatric transplant medicine. Further studies are warranted to explore additional risk factors and to refine prevention and treatment strategies for CMV in pediatric transplant recipients. Disclosures All Authors: No reported disclosures

P-2001. Limited Yield of Weekly SARS-CoV-2 Surveillance Testing Among Asymptomatic Hematopoietic Cell Transplant and Chimeric Antigen Receptor T-Cell Therapy Recipients

Abstract Background Surveillance testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among asymptomatic patients is used in some healthcare settings to prevent outbreaks. We examined the utility of weekly SARS-CoV-2 testing among asymptomatic hematopoietic cell transplant (HCT) and chimeric antigen receptor T-cell (CART) therapy recipients at a comprehensive cancer center. Methods We retrieved nasopharyngeal and nasal SARS-CoV-2 polymerase chain reaction (PCR) results and test indications from a cohort of HCT and CART recipients from April 30, 2021 to March 1, 2023, when weekly asymptomatic surveillance was performed. Test results were captured between patients’ Center arrival dates and either discharge home, day before a second HCT or CART infusion, death, date of last contact, or March 1, 2023. Only the first positive test per patient was included in the analysis; positive test results prompted chart review to determine false positives, symptom development, and impact on cancer care.Figure 1.Weeks of isolation among 32 patients testing positive for SARS-CoV-2 from asymptomatic weekly surveillance testing. Empty bars represent patients with asymptomatic infection (n=14), light gray bars represent those who developed symptoms (n=14), and black bars represent false positives (n=4). Results 8863 PCR tests were obtained from 809 patients, including 8560 weekly surveillance tests from 807 asymptomatic patients (median of 10 tests per patient, range 1-29), and 303 tests from 238 symptomatic patients. Tests performed among asymptomatic patients were less frequently positive (0.4%) than those performed among symptomatic patients (5.6%; Table 1). Of the 32/807 (4%) patients testing positive by asymptomatic weekly surveillance, 14 (44%) developed symptoms consistent with Coronavirus Disease 2019 (COVID-19), 14 (44%) were asymptomatic, and 4 (13%) were false positives. The 32 positive patients were isolated for a median of 22 days (range 0-266) (Fig 1). 13 (41%) patients with true positives and 1 (3%) patient with a false-positive had delays in cancer care (Fig 2).Figure 2.Percentage of patients with delays in procedures or treatment, among 32 patients testing positive for SARS-CoV-2 from asymptomatic weekly surveillance testing. Includes 19 patients testing positive pre-HCT/CART and 17 testing positive post-HCT/CART. Procedures were defined as medical interventions required prior to HCT or CART (e.g., port placement, pulmonary function tests). Treatment was defined as therapeutic agents/modalities associated with cancer care, including HCT or CART. Empty bars represent patients with asymptomatic infection (4 with procedure delay, 4 with treatment delay), light gray bars represent those who developed symptoms (0 with procedure delay, 7 with treatment delay), and black bars represent false positives (1 with procedure delay, 0 with treatment delay). Two patients had delays in both procedures and treatment; 14/32 (44%) had delays in either procedures or treatment. Conclusion Weekly SARS-CoV-2 surveillance testing among asymptomatic yet high-risk HCT and CART patients at a comprehensive cancer center over a two-year period identified 28 patients (3% of those tested) with pre-symptomatic or asymptomatic infection. Considering costs of screening, and effectiveness of infection prevention strategies, including symptom screening, universal masking, and access to rapid symptomatic testing, our data suggest limited value of weekly asymptomatic screening in this setting. Disclosures Steven A. Pergam, MD, MPH, Cidara: Advisor/Consultant|F2G: Advisor/Consultant|Global Life Technologies: Grant/Research Support|Symbio: Advisor/Consultant Catherine Liu, MD, Pfizer: Grant/Research Support

P-2298. Daily Single-strength vs. Thrice-weekly Double-strength Trimethoprim/sulfamethoxazole for Pneumocystis jirovecii Prophylaxis in Kidney Transplant Recipients: A Non-inferiority Randomized Controlled trial

Abstract Background Pneumocystis jirovecii pneumonia (PCP) is commonly encountered among kidney transplant (KT) recipients. Either daily or thrice-weekly, single strength (SS) or double strength (DS) trimethoprim/sulfamethoxazole (TMP/SMX) is recommended after KT to prevent PCP. However, a direct comparison between these regimens in terms of PCP prevention is lacking. We assessed the efficacy of SS daily (DSS) versus DS thrice weekly (TDS) TMP/SMX prophylaxis for PCP within the first 6 months post-transplant in KT recipients. Methods We conducted a single-center block of 4 randomized, open-label, non-inferiority, randomized controlled trial at a single transplant center between December 2022 and December 2023. All KT recipients 15 years and older were included. The single-strength group received TMP/SMX 80/400 mg daily after KT, while the double-strength group received two tablets of SS doses thrice weekly. PCP occurrence was observed for 6 months, and side effects of TMP/SMX and ease of drug consumption were monitored. Results A total of 65 KT recipients were included. The participants had a mean age (SD) of 46 (11) years old, with the following proportion: male gender (58%), deceased donor KT (20%), anti-thymocyte globulin as induction therapy (17%), and CMV seropositivity (95%). There were 32 and 33 KT recipients assigned to the DSS and TDS groups, respectively. Baseline characteristics between the two groups were comparable. At 6 months after transplant, all patients remained free from PCP in both groups. There was a non-significant lower mean (SD) of white blood cell counts in the DSS group compared to the TDS group [6,235 (2,271) vs.7,052 (2,464) cells/mm3, p = 0.23], respectively. In parallel, there was no significant difference in terms of hepatotoxicity or renal dysfunction among those groups. According to per-protocol analysis, 27 (96%) of the DSS group reported having convenient administration of the drug compared to 18 (100%) of the TDS group (p = 0.60). Conclusion TMP/SMX appears to efficiently prevent PCP in the early period after KT. Both SS daily and DS thrice-weekly regimens seem to be comparable in terms of effectiveness, tolerability, and compliance. Further studies with larger samples are encouraged to support this result. TCTR20240329004. Disclosures All Authors: No reported disclosures

γδ T Cells’ Role in Donor-Specific Antibody Generation: Insights From Transplant Recipients and Experimental Models

The generation of donor-specific antibodies (DSA) requires that alloreactive B cells receive help from follicular helper T (TFH) cells. Recent works have suggested that γδ T cells could contribute to T cell-dependent humoral responses, leading us to investigate their role in DSA generation. Analysis of a cohort of 331 kidney transplant recipients found no relation between the number of circulating γδ T cells and the risk to develop DSA. Coculture models demonstrated that activated γδ T cells were unable to promote the differentiation of B cells into plasma cells, ruling out that they can be “surrogate” TFH. In line with this, γδ T cells preferentially localized outside the B cell follicles, in the T cell area of lymph nodes, suggesting that they could instead act as “antigen-presenting cell” (APC) to prime αβ TFH. This hypothesis was proven wrong since γδ T cells failed to acquire APC functions in vitro. These findings were validated in vivo by the demonstration that following transplantation with an allogeneic Balb/c (H2d) heart, wild-type and TCRδKO C57BL/6 (H2b) mice developed similar DSA responses, whereas TCRαKO recipients did not develop DSA. We concluded that the generation of DSA is unfazed by the absence of γδ T cells.

P-42. Systematic review and meta-analysis of recombinant herpes zoster vaccine in immunocompromised populations

Abstract Background Herpes zoster infection is common in immunocompromised individuals. Recently, the Advisory Committee on Immunization Practices recommended immunizing with the recombinant zoster vaccine (RZV). Methods Objective: To evaluate the efficacy, immunogenicity and safety of RZV in immunocompromised individuals, such as transplant recipients, cancer patients undergoing chemotherapy, individuals with preexisting autoimmune diseases and HIV-infected patients. Data Sources and Study Selection: From January 1984 to October 2023, a systematic search of PubMed, MEDLINE, EMBASE, Scopus, Web of Science, CINAHL, and Cochrane CENTRAL was performed. Randomized clinical trials (RCT) evaluating RZV compared to placebo in immunocompromised adults were selected. Data Extraction and Synthesis: Study characteristics and estimates on the incidence of herpes zoster, humoral and cellular immune responses, and safety data were extracted from studies. Estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were estimated using subgroup meta-analysis and metaregression. Results Seven RCTs were included. Compared to placebo, RZV reduced the incidence of herpes zoster across all ages by 81% (RR: 0.19, 95%CI: 0.09, 0.44), with moderate heterogeneity across the studies (I2 = 60.49%; τ2 = 0.31; P=0.07). RZV significantly increased humoral and cellular immunity one month after the last dose. Transplant and past malignancy were associated with lower immunogenicity. RZV was more reactogenic with more local and systemic adverse events. There was no difference in serious adverse events or death between the vaccine and placebo arms. Conclusion This study suggests that RZV reduces the risk of herpes zoster infection in immunocompromised individuals. This vaccine should be routinely offered to immunocompromised individuals, preferably before chemotherapy or treatment. Disclosures All Authors: No reported disclosures

P-1161. Bacterial Bloodstream Infections in Pediatric Solid Organ Transplant Recipients within One Year of Transplant

Abstract Background Bacterial bloodstream infections (BSI) are a major cause of morbidity in immunosuppressed children, yet data are limited for pediatric solid organ transplant recipients (SOT). Prior studies have found varying rates of BSI in the first 2 years after pediatric transplant. This single center study investigated the incidence, risk factors and outcomes of pediatric SOT recipients who experienced a BSI within 1 year of transplantation.Table 1.Patient demographics Methods Retrospective single-center study of pediatric heart, liver, or kidney transplant recipients undergoing their first transplant at Lurie Children’s between January 2010 and December 2023. The primary outcome measure was bacterial bloodstream infection (BSI) within one year of SOT (minimum follow-up three months).Table 2.Results for primary outcome Results A total of 582 patients under age 18 received a first SOT between January 1, 2010 and December 31, 2023 (Table 1). Overall incidence of BSI within one year of SOT was 8.6%. Rates were significantly higher in liver recipients (13.6%) than heart (7.4%) and kidney recipients (5.5%; P=0.02). Incidence was highest in patients transplanted between 1 and 5 years of age (15.7%) than in other age ranges (Table 2; P= 0.02). Among those with BSI, the median time to first episode after transplant was 20.5 days (IQR 11.3, 98.5; Table 3). The most common identified infectious source was a central venous catheter (Table 4), with 39 of the 49 episodes occurring while a central venous catheter was in place. The most common organisms identified were Klebsiella pneumoniae (8 patients), Staphylococcus epidermidis (7 patients), and Enterobacter cloacae (6 patients, 2 of whom had polymicrobial bacteremia). Overall incidence dropped significantly over the time frame analyzed, comparing those transplanted between 2010-14 (11.9%), between 2015-19 (8.9%), and 2020-2023 (4.3%); P=0.02.Table 3.Median time to first BSI after SOT Conclusion BSI within the first year after SOT is common in children, occurring at rates comparable to published data in adults. Children under 5 years of age had the highest rate, and presence of a central venous catheter was common during initial episodes. Further investigation is needed to identify more detailed risk factors associated with BSI in children receiving solid organ transplant, prevention strategies, and reasons contributing to the drop is BSI rates over time.Table 4.Organisms identified and source of infection Disclosures Larry K. Kociolek, MD, MSCI, Merck: Grant/Research Support William J. Muller, MD, Ansun Biopharma: Grant/Research Support|Astellas Pharma: Advisor/Consultant|Astellas Pharma: Grant/Research Support|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|DiaSorin: Advisor/Consultant|DiaSorin: Honoraria|Eli Lilly and Company: Grant/Research Support|Enanta Pharmaceuticals: Advisor/Consultant|Enanta Pharmaceuticals: Grant/Research Support|F. Hoffmann-LaRoche Ltd (Roche): Grant/Research Support|Finley Law Firm, P.C.: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Melinta Therapeutics, Inc.: Grant/Research Support|Merck Sharpe & Dohme: Grant/Research Support|Moderna: Grant/Research Support|Nabriva Therapeutics, plc: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|Pfizer: Grant/Research Support|ProventionBio: Advisor/Consultant|Sanofi: Advisor/Consultant|Sanofi: Honoraria|Tetraphase Pharmaceuticals, Inc.: Grant/Research Support

P-2227. Real-Life Utilization and Clinical Impact of Karius Testing in Solid Organ Transplant Recipients: A Retrospective Analysis

Abstract Background Metagenomic next-generation sequencing such as Karius test (KT), is increasingly being used for microbial detection in various clinical syndromes, including sepsis, Fever of Unknown Origin (FUO), pneumonia, and cardiovascular infection. However, data regarding the utility of KT in solid organ transplant recipients (SOTR) are lacking. There is a need to assess its clinical impact and appropriate use considering its cost, potential for detection of commensal organisms, and lack of antimicrobial susceptibility data. Our study focuses on the real-world clinical impact of KT in SOTR. Methods We performed a retrospective review of all adult SOTR who underwent KT at Baylor St Luke’s Medical Center from March 2017 to February 2023. Clinical impact (positive, neutral, and negative) was assessed using standardized objective criteria utilized in prior studies. Descriptive analysis with patient and clinical characteristics was completed. Results A total of 113 KT in liver (42%), kidney (35%), lung (20%) and heart (13%) transplant recipients were completed in the study period (Table 1). The most common clinical syndromes where KT was ordered included: pneumonia (36%), FUO (16%), and intrabdominal infections (15%). Majority (81, 72%) of the KT results were positive for microbiological organisms (Table 2). Overall, 52 (46%) of conventional microbiological tests (CT) were also positive. Ultimately, 27 (24%) of cases were identified with positive clinical impact from KT testing, 87 (77%) neutral, and 4 (4%) negative, respectively (Table 3). Conclusion In SOTR, KT can add a positive clinical impact and identify microorganisms beyond conventional microbiological testing across clinical syndromes. However, larger prospective studies are needed to define the optimal timing and utilization in diagnostic evaluation algorithms for syndrome-specific work-up in SOTR. Disclosures M. Rizwan Sohail, MD, Medtronic: Advisor/Consultant|Medtronic: Honoraria|Philips: Advisor/Consultant|Philips: Honoraria

P-694. Outcomes of respiratory viral infections in hematopoietic cell transplant recipients and patients with leukemia: a prospective study

Abstract Background Respiratory viral infections (RVIs) pose a significant clinical challenge in immunocompromised hosts, including patients with leukemia and hematopoietic cell transplant (HCT) recipients. Despite advances in infection prevention, diagnostics, and clinical management, RVIs continue to be a major cause of morbidity and mortality in this patient population, due to progression to lower respiratory tract infection (LRTI). We aimed to identify risk factors associated with progression to LRTI in patients with leukemia and HCT recipients.Table 1:Baseline characteristics and clinical outcomes of leukemia and Hematopoietic Cell Transplantation patients at enrollment with upper respiratory viral infections versus controls.1Continuous variables were compared using one-way ANOVA or Kruskal-Wallis rank sum test, and categorical data were analyzed using χ2 or Fisher's exact tests, as appropriate. P-value <0.05 was considered as statistically significant.Abbreviations: SARS-Cov, severe-acute-respiratory-syndrome-related coronavirus; AMML, acute myelomonocytic leukemia; CMML, chronic myelomonocytic leukaemia; BPDCN, blastic plasmacytoid dendritic cell neoplasm; AML, acute myeloid leukemia; MRD, matched related donor; MUD, matched unrelated donor; RSV, respiratory syncytial virus; IVIG, intravenous immunoglobulin; HFNC, high frequency nasal canula; GVHD, graft versus host disease. Methods From July 2021 through January 2024, we conducted a prospective observational study of patients with leukemia and HCT recipients. We included patients with RVI symptoms, a positive respiratory viral panel for respiratory syncytial virus (RSV), influenza, or parainfluenza (PIV) and normal chest radiography. Patients with RVI symptoms, normal chest radiography, but a negative respiratory viral panel were enrolled as controls. Outcomes of interest included progression to LRTI within 30 days, oxygen requirement, and 30- and 90-day all-cause mortality.Figure 1:Progression to lower respiratory infection in 30 days of follow-up according to study cohort (leukemia vs. post-HCT)Abbreviations: LRTI, lower respiratory tract infection; HCT, hematopoietic cell transplant Results Of 69 patients included, 36 (52%) had active leukemia and 33 (48%) were HCT recipients. Forty-eight (70%) patients had a diagnosis of RVI, including 17 (25%) RSV, 14 (20%) influenza, 17 (25%) PIV. We analyzed 21 (30%) control patients. During the follow-up period, 18 patients (11 HCT and 7 Leukemia) progressed to LRTI (Figure 1). In the LRTI group, we observed higher proportions of moderate and severe infections, based on maximal oxygen requirements within 30 days (p< 0.001), higher graft-versus-host disease diagnoses within 90 days following infection [5 (28%) vs 3 (6%), p=0.024, respectively], and increased 30- and 90-day all-cause mortality rates compared to patients to did not progress to LRTI [3 (17%) vs 0, p=0,016 and 5 (28%) vs 3 (6%), p=0.024, respectively]. Patients diagnosed with PIV were more likely to progress to LTRI within 30 days of diagnosis (Figure 2), but Influenza and RSV infections were associated with a higher 90-day all-cause mortality (Figure 3).Figure 2:Progression to lower respiratory infection in 30 days of follow-up according to respiratory viral infection pathogen.Abbreviations: LRTI, lower respiratory tract infection; RSV, respiratory syncytial virus; PIV, parainfluenza Conclusion HCT recipients and leukemia patients with PIV were more likely to progress to LRTI, but LRTI from influenza and RSV infections were associated with higher 30- and 90-day mortality.Figure 3:90-day mortality according to RVI pathogen.Abbreviation: RSV, respiratory syncytial virus; PIV, parainfluenza Disclosures Fareed Khawaja, MBBS, Eurofins Viracor: Grant/Research Support|Symbio: Grant/Research Support Kenneth J. Gollob, Ph.D., BMS: Honoraria|BMS: Gave a seminar on immuno-oncology|GSK: Grant/Research Support Roy F. Chemaly, MD/MPH, AiCuris: Advisor/Consultant|AiCuris: Grant/Research Support|Ansun Pharmaceuticals: Advisor/Consultant|Ansun Pharmaceuticals: Grant/Research Support|Astellas: Advisor/Consultant|Eurofins-Viracor: Grant/Research Support|InflaRX: Advisor/Consultant|Janssen: Advisor/Consultant|Karius: Advisor/Consultant|Karius: Grant/Research Support|Merck/MSD: Advisor/Consultant|Merck/MSD: Grant/Research Support|Moderna: Advisor/Consultant|Oxford Immunotec: Advisor/Consultant|Oxford Immunotec: Grant/Research Support|Roche/Genentech: Advisor/Consultant|Roche/Genentech: Grant/Research Support|Shinogi: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Grant/Research Support|Tether: Advisor/Consultant

P-912. A 10-Year Retrospective, Single-Center Analysis of Nocardiosis in Immunocompetent and Immunocompromised Hosts: Clinical and Microbiological Features, Treatment Outcomes, and Determinants of Central Nervous System Involvement

Abstract Background Nocardia species are organisms with the potential to affect numerous organ systems, including the brain. However, it is unknown whether specific host or microbe factors are associated with central nervous system (CNS) nocardiosis and whether outcomes for CNS nocardiosis differ according to host immune status. Demographics and clinical characteristics by immune status. SOTr: solid organ transplant recipient. SCTr: stem cell transplant recipient. MSK: musculoskeletal structure, such as bone or joint. COPD: chronic obstructive pulmonary disease. WBC: white blood cell count. *The isolation of Nocardia in 2 or more non-contiguous body sites constituted disseminated disease Methods We performed a retrospective review of all adults admitted to Yale New Haven Hospital with laboratory-confirmed nocardiosis from 2013 to 2023. CNS involvement was defined as the identification of Nocardia spp on brain tissue or new radiological brain lesions in a patient with extra-neural nocardiosis. We performed multivariate logistic regression analyses of clinical and microbiological variables related to CNS involvement. Nocardia species distribution by CNS involvement Results 94 patients were included, of which 63 (67%) were immunocompromised (Table 1). The most common immunocompromising conditions were recipients of solid organ transplants (32%) and stem cell transplants (22%). Sixteen (17%) patients had CNS involvement of their nocardiosis; this included 22% of immunocompromised and 6% of immunocompetent patients (p=.056). The most common species isolated was the Nocardia nova complex (Table 2). Table 3 summarizes the univariate analysis of factors associated with CNS involvement. Black race [OR 3.7 (1.2-11.7), p=.03] and N. farcinica infection [OR 5.9 (1.8-19.3), p=.005] were associated with increased risk of CNS involvement. In a multivariate analysis, infection by N. farcinica was an independent risk factor for CNS involvement [OR 5.3 (1.5-18.7), p=.009]. There were no significant survival differences in immunocompromised hosts, with or without CNS disease, compared to immunocompetent hosts. Univariate analysis of demographic, host immune status and organism features associated with CNS involvement. Conclusion N. farcinica infection was identified as an independent risk factor of CNS involvement in patients with nocardiosis. Other factors related to the net state of immunosuppression were not associated with an increased risk for CNS involvement. Disclosures All Authors: No reported disclosures

P-25. Evaluating the Immunogenicity and Safety of Either Two High-Dose or Two Standard-Dose Influenza Vaccines Over Two Consecutive Seasons in Adult Hematopoietic Cell Transplant Recipients

Abstract Background Adult hematopoietic cell transplant (HCT) recipients are at high risk of influenza complications but have suboptimal immune responses to influenza vaccines. Our previous phase II trial in adult HCT recipients demonstrated that two doses of high-dose trivalent influenza vaccine (HD-TIV) were associated with higher hemagglutination inhibition (HAI) antibody responses than two doses of standard-dose quadrivalent influenza vaccine (SD-QIV), with similar safety profiles. This sub-study aims to characterize immunogenicity and safety of this vaccination strategy in consecutive influenza seasons. Methods A subset of participants from our initial study were re-enrolled in a consecutive season using the same dosing regimen. HAI titers were measured at baseline and 4–6 weeks post-vaccination for each dose in both years. We calculated the geometric mean fold rise (GMFR) in HAI titers and used linear mixed-effects models to determine adjusted geometric mean ratios (aGMRs). Injection-site and systemic reactions were documented for 7 days post-vaccination. Results A total of 43 participants were re-enrolled (n=20 for SD-QIV and n=23 for HD-TIV). Baseline characteristics were similar between groups (Table 1). In the second year, post-dose 1 GMFRs for both SD-QIV and HD-TIV were higher compared to post-dose 1 titers in the first year across all antigens (Table 2). HAI titers were higher for all post-vaccination visits and dose groups in the second year compared to the first year (Figure 1). aGMR comparisons between HD-TIV and SD-QIV favored HD-TIV for A/H1N1, A/H3N2, and B/Victoria antigens in both years, with statistical significance for A/H1N1 after a single dose in the second year (aGMR, 3.21; 95% CI,1.06–9.70). Injection-site and systemic reactions were generally similar between groups in year 2 (Figure 2).Figure 1.Point estimates and 95% confidence intervals for geometric mean HAI titers at visits 1, 2, and 3 in year 1, as well as visits 1, 2, and 3 in the repeater year (denoted by “R”), stratified by influenza antigens (A/H1N1, A/H3N2, B/Victoria, and B/Yamagata), and by dose group (standard-dose quadrivalent influenza vaccine [SD-QIV] and high-dose trivalent influenza vaccine [HD-TIV]). Note that B/Yamagata is not included in HD-TIV. Conclusion In the second year, a single dose of HD-TIV or SD-QIV was more immunogenic than two doses of the same formulation in the first year, with HD-TIV demonstrating superior immunogenicity against A/H1N1. The safety profile across both vaccine formulations were similar.Figure 2.Relative frequencies of any injection-site and systemic reactions within 7 days of each vaccination for both vaccine groups (standard-dose quadrivalent influenza vaccine [SD-QIV] vs high-dose trivalent influenza vaccine [HD-TIV]) following each vaccine dose. Disclosures Edgar T. Overton, MD, ViiV Healthcare: Employment Michael Ison, MD MS, GlaxoSmithKline: Grant/Research Support|UpToDate: Royalties Steven A. Pergam, MD, MPH, Cidara: Participate in company sponsored clinical trial|F2G: Participate in company sponsored clinical trial|Global Life Technologies: Grant/Research Support|Symbio: Participate in company sponsored clinical trial Natasha B. Halasa, MD, MPH, Merck: Grant/Research Support

P-2308. Effect of Antibiotic Therapy on Preventing Subsequent Urinary Tract Infection in Early Kidney Transplant Recipients with Asymptomatic Bacteriuria

Abstract Background The efficacy of treating asymptomatic bacteriuria during the early peri-transplantation period in kidney transplant (KT) recipient has not been properly assessed. In this study, we assessed the effectiveness of treating asymptomatic bacteriuria in first three months after KT and one month before, including bladder irrigation specimen obtained from operating room. Methods A single center retrospective cohort study was conducted on patient who underwent KT. KT recipient with asymptomatic bacteriuria within 30 days before and 90 days after the transplantation between January 2020 and January 2023 were included. The frequency of subsequent urinary tract infection (UTI) within 90 days of detecting asymptomatic bacteriuria was compared between antibiotic-treated and untreated groups. Results A total of 112 KT recipients with asymptomatic bacteriuria were included; of these, 33 (29 %) received antibiotic treatment while 79 (71 %) did not. Nineteen patients (17%) developed symptomatic UTIs within 90 days of detecting asymptomatic bacteriuria; 21% (7/33) in the antibiotic-treated group and 15% (12/79) in the untreated group (odds ratio, 1.53; 95% confidence interval, 0.53 to 4.24). Untreated asymptomatic bacteriuria was not significantly associated with subsequent UTI in multivariable logistic regression analysis (adjusted odds ratio, 1.32, 95% confidence interval, 0.45 to 3.85; p=0.61) after adjusting gender, vesicoureteral reflux, malignancy, type of donated kidney and induction immunosuppressive drug. Conclusion We found that antibiotic therapy for patients with asymptomatic bacteriuria during the early peri-transplantation period did not confera significant advantage in preventing subsequent UTIs. Prescribing antibiotics for asymptomatic bacteriuria in KT recipients should be approached with caution due to the potential risk of colonization or infection by resistant bacteria. Figure 1. Kaplan-Meier estimates of UTI incidence in patients with asymptomatic bacteriuria after KT ; Log-rank test showed that treated group showed that UTI occurred later than untreated group. (p=0.37) Disclosures All Authors: No reported disclosures

372. Impact of Updated 2020 Public Health Service Guidelines on Deceased Organ Donors and Transplant Recipients

Abstract Background New guidelines for assessing solid organ donors and recipients for Human Immunodeficiency Virus (HIV), Hepatitis B (HBV), and Hepatitis C (HCV) infection were published by the US Public Health Service (PHS) in 2020 and implemented into Organ Procurement and Transplantation Network (OPTN) policy on 3/1/21. Changes included a shorter risk criteria inclusionary timeframe and the removal of 4 risk criteria. Methods We analyzed OPTN deceased donor and transplant data 2 years pre-(3/1/19-2/28/21) and post-(3/1/21-3/1/23) implementation of the updated guidelines. For Kaplan-Meier survival analyses, the post- cohort included recipients transplanted before 1/1/23 to ensure recipients had at least 1 year follow-up plus a 3-month data lag. Utilization rates, defined as number of organs transplanted divided by number of available organs from donors with at least 1 organ recovered for the purpose of transplant, are shown for thoracic organs. Non-use rates, defined as number of organs recovered for the purpose of transplant but not transplanted divided by the total number of organs recovered for the purpose of transplant, are shown for abdominal organs. Results The proportion of donors considered to have PHS risk factors decreased by approximately 10% post-policy, both overall and by organ type (Fig. 1). There were no major differences pre- to post- in reported donor HIV, HCV or HBV NAT test results (Fig2. ). Post-policy, utilization rates for heart and lung for donors with risk factors were 34.9% and 17.5% respectively, compared to 34.3% and 20.0% pre-policy; while kidney and liver non-use rates for donors with risk factors were 20.3% and 8.2% respectively, compared to 17.2% and 7.9% pre-policy. There was no significant change in 1-year post-transplant patient survival for recipients who received organs from donors with PHS risk factors (Fig. 3). Conclusion Less restrictive PHS guidelines led to fewer donors being classified as having risk factors for disease transmission. Updated guidelines did not significantly affect donor infectious disease test results or post-transplant survival for recipients. Changes in donor organ utilization and non-use may be due to donor pool changes and/or overlapping policy implementations, and further investigation is warranted. Disclosures Lara A. Danziger-Isakov, MD, MPH, Aicuris: clinical research contract, paid to institutio|Ansun BioPharma: clinical research contract, paid to institution|Astellas: Advisor/Consultant|Astellas: clinical research contract, paid to institutio|Merck: clinical research contract, paid to institutio|Pfizer: Grant/Research Support|Takeda: clinical research contract, paid to institutio

P-648. Shorter vs Standard-Duration Antibiotic Therapy for Nocardiosis: A Multicenter Retrospective Cohort Study

Abstract Background The recommendation to treat nocardiosis for long durations (usually 6-12 months) relies on small case series published decades ago. We implemented real-world data to assess the association between treatment duration and outcomes in nocardiosis.Table 1.Clinical characteristics and outcomes of individuals diagnosed with nocardiosis, according to treatment duration rangea Calculated for the three treatment groups using Chi-square test or Fisher’s exact test (⸙) and one-way ANOVA for categorical and continuous variables, respectively; b Average daily prednisone dosage (in milligrams), during the 90 days prior to presentation. Whenever dexamethasone was used, dosage was converted to the equivalent prednisone dosage; c Individuals with active malignancy, primary immune deficiency, autoimmune diseases, and chronic corticosteroid therapy (≥5 and <20 mg per day); d Solid organ transplant recipients, hematopoietic stem cell transplant recipients, and individuals with acquired immunodeficiency syndrome (AIDS) or on chronic corticosteroid therapy (≥20 mg per day); e Identification to the species level was available for 95/176 (54%) of the cohort. IV = intravenous; NA = not applicable; SMX-TMP = sulfamethoxazole-trimethoprim. Methods A multicenter retrospective cohort study comprising individuals with nocardiosis during 2007-2022, excluding those who died within 90 days from diagnosis. Patients were classified into three groups according to treatment duration: short (≤90 days), intermediate (91-180 days), and long ( >180 days). We compared overall mortality, relapse rates, and antibiotic-related adverse events at 1-year. Treatment duration was cross tabulated with immune status and nocardiosis syndrome, considering that clinical judgment has led physicians to deviate from recommended long durations in appropriate cases.Figure 1.Study flow diagram Results A total of 176 individuals were diagnosed with nocardiosis during the study period, 43 (24%) of whom died within 90 days and were excluded (Figure 1). Of the remaining 133 individuals, 45 (34%) were apparently immunocompetent, 26 (19%) and 62 (47%) had mild-moderate and substantial immune suppression, respectively. Patients received short (N=37, 28%), intermediate (N=40, 30%) and long (N=56, 42%) treatment durations. Longer treatment duration was positively associated with systemic corticosteroid use (p=0.009), immune suppression (p=0.014), and nocardiosis syndrome (longer durations for dissemination, p=0.001; Table, Figure 2). By 1-year, 20 (15%) individuals died and 2 (1.5%) relapsed. Treatment duration was not associated with mortality (p=0.977; Figure 3) or nocardiosis relapse (p=0.509). Of those with solitary pulmonary nocardiosis (N=73), none of the 20 immunocompetent individuals died by 1-year, while 5/16 (31%), and 6/37 (17%) of those with mild-moderate and substantial immune suppression, respectively, died, regardless of treatment duration. Adverse events rate did not differ significantly between duration groups.Figure 2.Distribution of treatment duration groups according to nocardiosis clinical syndrome and immune status For each color, shades signify immune status (apparently immunocompetent individuals, and those with mild-moderate or substantial immune suppression): darker shades signify diminished immunity. Conclusion With clinically guided case-by-case patient selection nocardiosis can be safely treated for durations significantly shorter than traditionally recommended.Figure 3.Survival curves of the entire cohort, according to treatment group The entire cohort is presented as a single curve up to 90 days, then divided into 3 treatment groups, according to the total treatment duration. p value calculated using Log-rank test. Disclosures All Authors: No reported disclosures

P-400. Surgical Site Infections among Heart Transplant, Lung Transplant, and VAD Inserted Patients

Abstract Background Surgical site infections (SSI) after heart and lung transplantation and implantation of Ventricular Assist Devices (VAD) confer significant morbidity. Despite this, many sites do not perform routine surveillance of this population. Considering the paucity of available data, this retrospective chart review evaluated the incidence, risk factors, associated microorganisms, and outcomes associated with surgical site infection by type of transplant received. Methods This review was conducted at a tertiary care hospital in Edmonton, Alberta. All patients who received a heart or lung transplant or VAD insertion between July 1, 2022, and December 31, 2023, that had at least 90 days of follow-up were included. Information collected included data on transplant/VAD insertion, age, sex, presence of SSI, microorganisms associated with infection, length of stay, and outcome. Other data collected included receipt of antibiotic prophylaxis, admission to hospital in the six months prior to transplant, and surgery in the six months prior to transplant. Results A total of 219 patients were included in the review (double lung transplant = 104, heart transplant = 38 and VAD insertion = 77) SSI rate was found to be higher in the VAD insertion group (16%), compared to lung (12.5%) or heart transplant (7.8%) recipients. Post-transplant hospital stay was longer in lung transplant (17-131; median 55) and heart transplant recipients (81-115; median 112) who developed SSI, compared to their counterparts who did not develop SSI (12-197; median 32 and 13-120; median 20 respectively). Coagulase-negative staphylococcus aureus was found to be the most common pathogen among all three groups of transplants that developed surgical site infections (SSIs). However, Cutibacterium acne was also frequently isolated in VAD recipients, while Yeast, E. fecalis and E. feceium were commonly found to be responsible for lung transplant SSIs. Conclusion Rates of SSI after heart and lung transplantation and VAD insertion are high and result in significant morbidity. The choice of antibiotic prophylaxis may need to be individualized in this patient population given prior antibiotic exposure, hospitalization, and risk of more resistant pathogens. Disclosures All Authors: No reported disclosures

P-2254. Incidence, Clinical Characteristics and Outcomes of Heart Transplant Patients with Mucormycosis Infection: A Systematic Review and Meta-Analysis

Abstract Background Mucormycosis confers high morbidity and mortality in the immunocompromised population due to its rapid angio-invasive nature. Of note, this group of people includes those who have undergone solid organ or stem cell transplants, many of whom are placed on chronic immunosuppressive regimens. Mucormycosis incidence and clinical outcomes have been studied in bone marrow, lung, liver and kidney transplant recipients but not in heart transplant patients. Thus, our aim with this systematic review and meta-analysis is to characterize the incidence as well as clinical outcomes of Mucor infections in heart transplant recipients.Figure 1.PRISMA Flowchart Methods This study was registered with PROSPERO. Electronic databases Google Scholar, PubMed, Embase, Scopus and CINAHL were searched from inception up to 1 February 2024 for peer-reviewed articles of heart transplant patients who contracted mucormycosis. The primary and secondary outcome measures were incidence of mucormycosis infection and times to onset of infection and mortality, respectively. For statistical analysis, overall meta-analytic incidence was estimated using the user-written metaprop_one[FD1] [m2] command in Stata 15.1.Table 1.Species Identified in Infection Results Our search identified 296 studies, 88 of which underwent full-text review and 47 met inclusion criteria with 3916 total cases (Figure 1). Rhizopus was the most common pathogen identified causing mucormycosis infection (Figure 2). Pooled incidence of mucormycosis infection in heart transplant patients is 0.6% (95% CI 0 - 2%) across 12 studies (Figure 3). The majority of patients were male, 39/41 (95%) (Figure 4). Mucormycosis infection most commonly occurred during first 30 days post-transplant and decreased with time. Logistic regression analysis did not show significant association between time of infection post-transplant and mortality: Odds Ratio = 0.89 (95% CI 0.55-1.42, p = 0.616).Figure 2.Results of Meta-Analysis for Incidence of Mucormycosis Infection in Heart Transplant Recipients Conclusion Overall incidence of mucormycosis in heart transplant patients is 0.6%. Patients were more likely to contract the infection early (within 30 days) in the post-transplant period but there was no significant difference in mortality over time. The majority of affected patients were male and further studies are needed to determine if males are at higher risk of infection.Table 2.Demographics and Time of Infection Onset Disclosures All Authors: No reported disclosures

P-1962. SEAL: Serology-based Assessment of Evusheld in Lung Transplant Recipients

Abstract Background The primary strategy to combat severe COVID-19 infection in Lung Transplant Recipients (LTRs) is prevention through vaccination or the use of monoclonal antibodies such as Evusheld (tixagevimab/cilgavimab), for pre-exposure prophylaxis. Data on Evusheld efficacy overall and particularly in relation to the serological status of LTRs is scarce. We evaluated treatment outcomes in LTRs within 1 year after treatment with Evusheld based on their serological status before Evusheld administration. Study Design Of the 103 Lung Transplant recipients (LTRs*) who received Evusheld, 101 patients had been tested for anti-spike antibodies against SARS-CoV-2 prior to receiving Evusheld. 61 patients tested positive (seropositive) and 40 tested negative (seronegative). All patients were followed for 12 months. Outcomes were evaluated after the first 6 months when Evusheld was active, and after the second 6 months when Evusheld either was not used or had lost its efficacy against circulating strains. Methods This is a retrospective cohort analysis of 103 LTRs treated with Evusheld between January 27 and May 25, 2022, at Corwell Health in West Michigan. LTRs were classified into seropositive (SeroPos) and seronegative (SeroNeg) groups based on the presence of anti-spike antibodies against SARS-CoV-2 before Evusheld administration and evaluated after the first 6 months, when Evusheld was active, and after the second 6 months, when Evusheld was ineffective against circulating strains (Figure 1), for outcomes listed in Figure 2. We identified patients with positive COVID-19 test, either antigen or PCR. Morbidity was assessed through the rate of ED visits, hospital, and ICU admissions within 30 days from COVID-19 diagnosis. Mortality was assessed through COVID-19-related and all-cause deaths throughout the study period. Results Of 103 LTRs, 97% were vaccinated, 19% had COVID-19 and 59% were SeroPos before receiving Evusheld. Compared with SeroNeg LTRs, SeroPos LTRs were more likely to have had prior COVID-19 infection (22.95% v 12.5%, p=0.19). Vaccination rate was similar in both groups (98.36 vs 95%, p=0.56). SeroNeg LTRs were overall more likely to contract COVID-19, with a stable infection rate of 15% across the whole study period. In SeroPos LTRs, the positivity rate doubled in the 2nd 6 months compared with the 1st 6 months (6.5% vs. 13%, p=0.24). There was no difference in the disease severity between SeroPos and SeroNeg patients at any point (Figure 3). Overall, LTRs were less likely to contract COVID-19, be admitted to the hospital/intensive care unit, or die during the first 6 months when Evusheld was effective, compared with the second 6 months, but the difference was not statistically significant. (Figure 4). Characteristics and outcomes in seropositive and seronegative groups Conclusion Overall COVID-19 infection outcomes in LTRs had tendency to be better with Evsuheld use. SeroNeg LTRs were more likely to contract COVID-19 with and without Evusheld protection but serological status may not correlate with the disease severity. Our findings suggest that prior COVID-19 infection may induce a stronger immune response than the vaccine in LTRs. Outcome in all Lung Transplant Recipients Treated with Evusheld Lung transplant recipients were more likely to contract COVID-19 (13.73% vs. 9.71%, p=0.37), visit Emergency Department (ED (4.9% vs. 4.85%, p=1), get admitted to hospital (5.88% vs. 2.91%, p=0.33) or Intensive Care Unit (ICU) (1.96% vs. 0%, p=0.25), within the second 6 months compared with the first 6 months. All-cause mortality was significantly higher in the second 6 months (8.82% vs. 0.97%, p= 0.0097) but there was no difference in COVID-19 related deaths (0.98% vs. 0%, p=0.5). Disclosures All Authors: No reported disclosures

P-2275. Impact of Epstein-Barr Virus (EBV) Donor Serostatus on Post-transplant Mortality and Post-Transplant Lymphoproliferative Disorder in Thoracic Organ Transplant EBV-Seropositive Recipients: Data from the Organ Procurement and Transplantation Network

Abstract Background Epstein Barr Virus (EBV) donor positive (D+) serostatus is a risk factor for Post-Transplant Lymphoproliferative Disorder (PTLD) in EBV-seronegative recipients. The impact of donor EBV serostatus on mortality and PTLD in EBV-seropositive recipients (R+) in thoracic organ transplant (TOT) is unknown.Table 1.Baseline demographic and clinical characteristics of EBV D-/R+ and EBV D+/R+ TOT recipients Methods Using the Organ Procurement and Transplantation Network database, we identified 47,201 EBV R+ TOT recipients between 01/2004 – 12/2021. The primary exposure was EBV D+ and the primary outcomes were death and PTLD. Multivariable Cox regression models were used to assess the relationship between donor EBV serostatus and the outcome of death and PTLD.Figure 1.Kaplan-Meier survival plots for EBV D-/R+ (solid line) versus EBV D+/R+ (dashed line) post heart (red line) and lung (blue line) transplantation Results Of 47,201 EBV R+ TOT recipients, 48.5% were lung and 51% were heart transplant recipients. The majority (93.4%) were EBV D+/R+, with median age of 59 years and 66.8% males. EBV D-/R+ and D+/R+ TOT recipients differed in CMV donor and recipient status, donor median age, sex, and graft failure (Table 1). The incidence rate of death was 7.2 per 100 person-years in EBV D+/R+ compared to 6.9 per 100 person-years in EBV D-/R+, p=0.156. Survival did not differ by EBV donor status, but it was lower in lung transplant (Figure 1). The incidence rate of PTLD was 0.26 per 100-person years in EBV D+/R+ compared to 0.33 per 100-person years in EBV D-/R+, p= 0.073. EBV D+ status was not associated with increased hazard of death in both univariable (crude hazard ratio [HR] of 1.05; confidence interval [CI], 0.98-1.11; p=0.15) and multivariable analyses (adjusted HR of 0.96; 95% CI, 0.90-1.02; p=0.14), after controlling for donor age, CMV D+ status, and the following recipient factors: age, sex, race, insurance, pre-transplant life support, pre-transplant malignancy, rejection, and graft failure. EBV D+ status was associated with decreased hazard of PTLD when adjusting for recipient age and graft failure (adjusted HR of 0.74; 95% CI, 0.56-0.98; p=0.03). In subgroup analyses by organ, EBV D+ status was associated with decreased hazard of PTLD in lung (adjusted HR of 0.56; 95% CI, 0.40-0.78; p=0.001) but not in heart transplant recipients (adjusted HR of 1.18; 95% CI, 0.71-1.96; p =0.50) (Figure 2).Figure 2.Kaplan-Meier PTLD-free survival plots for EBV D-/R+ (solid line) versus EBV D+/R+ (dashed line) post heart (red line) and lung (blue line) transplantation Conclusion Among EBV-seropositive TOT recipients, EBV D- status may be associated with increased risk of PTLD, particularly in lung transplant recipients. Disclosures Alissa J. Inc, MD, MSc, Takeda: Honoraria Sara Belga, MD, MPH, Takeda, Moderna, AstraZeneca, GSK: Advisor/Consultant|Takeda, Moderna, AstraZeneca, GSK: Grant/Research Support|Takeda, Moderna, AstraZeneca, GSK: Honoraria

P-1036. Invasive fungal Rhinosinusitis in solid organ and hematopoietic stem cell transplant recipients at a tertiary care center in the United States

Abstract Background Solid organ (SOT) and hematopoietic stem cell transplant (HSCT) recipients are at increased risk of invasive fungal infections. Invasive fungal rhinosinusitis (IFRS) post-transplant has not been well studied due to limited information in large databases. We present the epidemiology of IFRS in SOT and HSCT.Table 1:Summary of SOT with invasive fungal rhinosinusitis cases: Methods Retrospective study 2010–2022: we identified all cases of IFRS through pathology database. Demographics, organ transplant, immunosuppression, antimicrobial prophylaxis, surgical and medical treatment, and outcomes were examined. IFRS diagnosis was based on histopathological evidence of invasion through the nasal or sinus mucosa or deeper tissue.Table 2:Summary of the hematopoietic stem cell transplant with invasive fungal rhinosinusitisAbbreviations: MMF, Mycophenolate Mofetil; Tac,tacrolimus; Pred,prednisone; BAS, Basiliximab; HC, hydrocortisone; MethylP, Methylprednisolone; ATG, antithymocyte Globulin; DDC, Dapsone; CLT, clotrimazole; VGV, valganciclovir; PTMD, Pentamidine; NST, nystatin; TMP/SXT, trimethoprim–sulfamethoxazole; LVX, levofloxacin; ACV, ayclovir; MCF,Micafungin; ASPE FUMI,Asperigillus fumigatus ; ASPE FLAV,asperigullis flavus; VCZ,Voriconazole; L-AMB,Liposomal Amphoterecin b ; PSC,Posaconazole ; ALEM, alemtuzumab; FLZ, fluconazole; ISV, isavuconazole; AMOX, amoxicillin; VALACY,valacyclovir; LTV,Letermovir ;MUD, matched unrelated donor;HCT, hematopeitic stem cell Results Of 101 IFRS cases, 17 were transplant: 5 SOT, 12 HSCT. Mean age for SOT was 55 (range 28–73 years). Organs included 3 kidneys, 1 intestine, 1 liver. Med. time to IFRS after SOT was 1245 d (IQR 102–1772). Aspergillus fumigatus was identified in 3 (60%), Rhizopus spp. in 1 (20%), and Alternaria alternata in 1 (20%). 1 had acute rejection treatment. 2 had CMV viremia. All 5 received surgical and medical interventions. Voriconazole (VCZ) was given to 3 patients along with liposomal amphotericin B (LAmB) and micafungin (Table 1). Mortality was 40%. For HSCT, mean age was 46 (range 30-78 years). 42% HSCT were matched unrelated donor, 25% haploidentical, 25% HLA-matched sibling, and 8% autologous. Med. time to IFRS after HSCT was 254 d (IQR 39–576). Mucormycosis was diagnosed in 4 (33%), Aspergillus spp. in 2 (17%), Fusarium solani in 1 (8%), and combined Absidia spp./ Alternaria alternata in 1 (8%); 4 (33%) causative pathogen was not identified. 67% experienced hematologic disease relapse and were undergoing treatment. 25% had CMV. 17% had acute GVHD treatment. 6 (50%) IFRS occurred on antifungal prophylaxis (4 fluconazole, 1 isavuconazole, 1 VCZ). All 12 had surgical and medical management. 10 were treated with LAmB, 1 VCZ, 1 posaconazole (Table 2). Even without intracranial extension, mortality was 83% (Figure 1). Conclusion IFRS continues to be associated with high mortality among contemporary patients. Our observations identify important disease differences depending on SOT versus HSCT status. Data analyzing predictors of death and other important outcome measures such as neurologic disability are needed. Disclosures All Authors: No reported disclosures

636. Pneumocystis Pneumonia Outcomes in Solid Organ Transplant Recipients and Patients Living with HIV: A Population-Based Study Over 20 Years (2002-2022) in Ontario, Canada

Abstract Background While it is well established that HIV-positive and non-HIV immunocompromised patients are susceptible to Pneumocystis pneumonia (PCP), comparing PCP outcomes between patients with different underlying immunocompromising conditions is critically important to optimize chemoprophylaxis strategies. Methods In this population-based cohort, we determined contributing factors to 90-day all-cause mortality following PCP diagnosis among patients living with HIV (PLWH) and solid organ transplant recipients (SOTRs) hospitalized in Ontario, Canada between Apr/1/2002 and Dec/31/2022. We linked data from provincial health administrative databases using unique encoded identifiers and included all adult patients hospitalized with PCP based on diagnostic codes from hospital discharge abstracts. We used logistic regression models to estimate unadjusted and adjusted odds ratios (uOR and aOR) and 95% confidence intervals (95%CI) for the associations between underlying immunocompromising conditions and PCP outcomes. Results A total of 879 patients were hospitalized with PCP, including 121 SOTRs (13.7%) and 758 PLWH (86.2%). 90-day mortality rates were 19.8% in SOTRs and 13.2% in PLWH. In the unadjusted model, 90-day mortality was not significantly associated with organ transplantation (OR=1.58; 95%CI, 0.96-2.62) or HIV infection (OR=0.62; 95%CI, 0.38-1.03). Comparing HIV patients to liver SOTRs, liver SOTRs experienced higher mortality (uOR=8.54, 95%CI=3.11-23.46). In the adjusted model, liver transplantation was associated with an increased risk of 90-day mortality (aOR=4.36; 95%CI, 1.40-13.59). Among SOTRs, in the unadjusted analysis, liver transplant recipients had an increased risk of 90-day mortality (uOR=9.18; 95%CI, 3.00-28.09). Conclusion Among SOTRs, liver transplant recipients are at particularly higher risk of mortality following PCP diagnosis. Our findings may prompt a re-evaluation of current PCP prophylactic strategies in liver transplant patients. Disclosures All Authors: No reported disclosures